PMID- 25844238
TI - Crystal structure of 1-butyl-2,3-di-methyl-imidazolium dicarba-7,8-nido-undeca
borate.
AB - In the title mol-ecular salt, C9H17N2 (+).C2H12B9 (-), the carborane cage has a
bridging B-H-B bond on the open B3C2 face. The butyl side chain of the cation
adopts an extended conformation [C-C-C-C = 179.6 (1) degrees ]. In the crystal,
the imidazolium ring is almost coplanar with the open face of the carborane
anion. The cations stack in the [010] direction and the dihedral angle between
the imidazolium rings of adjacent cations is 68.45 (6) degrees . The butyl chains
extend into the space between carborane anions.
PMID- 25844239
TI - Crystal structure of 2-[(3S,4S)-4-(anthracen-9-yl)-1-(4-meth-oxy-phen-yl)-2
oxoazetidin-3-yl]-2-aza-2H-phenalene-1,3-dione unknown solvate.
AB - The central beta-lactam ring of the title compound, C36H24N2O4, is almost planar
(r.m.s. deviation = 0.003 A) and makes dihedral angles of 17.17 (19), 89.76 (17)
and 78.44 (17) degrees with the benzene ring, the anthracene ring (r.m.s.
deviation = 0.003 A) and the 1H-benzo[de]iso-quinoline-1,3(2H)-dione moiety,
which is nearly planar [maximum deviation = 0.098 (2) A], respectively. The mol
ecular structure is stabilized by an intra-molecular C-H?N hydrogen bond. In the
crystal, mol-ecules are linked via C-H?pi and pi-pi stacking inter-actions
[centroid-centroid distances = 3.5270 (19) and 3.779 (2) A], forming a three
dimensional structure. A region of disordered electron density, probably
disordered solvent mol-ecules, was treated with the SQUEEZE procedure in PLATON
[Spek (2015 ?). Acta Cryst. C71, 9-18], which indicated a solvent cavity of 322
A(3) containing approximately 91 electrons. Their formula mass and unit-cell
characteristics were not taken into account during the refinement.
PMID- 25844240
TI - Crystal structure of 2-hydroxy-N-(2-hydroxyethyl)-N-{2-hydroxy-3-[(E)-N
hydroxyethanimidoyl]-5-methylbenzyl}ethanaminium acetate monohydrate.
AB - The structure of the title hydrated mol-ecular salt, C14H23N2O4 (+).C2H3O2 (
).H2O, was determined as part of a wider study on the use of the mol-ecule as a
polydentate ligand in the synthesis of Mn(III) clusters with magnetic properties.
The cation features intra-molecular O-H?N and N-H?O hydrogen-bond inter-actions.
The crystal structure features a range of inter-molecular hydrogen-bonding inter
actions, principally O-H?O inter-actions between all three species in the
asymmetric unit. An R (2) 4(8) graph-set hydrogen-bonding motif between the anion
and water mol-ecules serves as a unit which links to the cation via the di-ethano
lamine group. Each O atom of the acetate anion accepts two hydrogen bonds.
PMID- 25844241
TI - Crystal structure of methyl (E)-2-(1-methyl-2-oxoindolin-3-yl-idene)acetate.
AB - The title compound, C12H11NO3, is essentially planar, with the mean plane of the
acetate side chain [-C-C(=O)-O-C] being inclined to the mean plane of the indole
ring system by 12.49 (7) degrees . The five- and six-membered rings of the indole
group are almost coplanar, making a dihedral angle of 1.76 (8) degrees . The
conformation about the C=C bond is E and there is an intra-molecular C-H?O
hydrogen bond present. In the crystal, mol-ecules are linked by pairs of C-H?O
hydrogen bonds forming inversion dimers, with an R 2 (2)(16) ring motif. The
dimers are linked by a second pair of C-H?O hydrogen bonds, enclosing R 2 (2)(16)
ring motifs, forming ribbons lying parallel to (-114). The ribbons are linked via
C-H?pi inter-actions, forming a three-dimensional structure.
PMID- 25844242
TI - Crystal structure of 2-{[(naphthalen-1-yl)oxy]meth-yl}-5-(2,4,5-tri-fluoro-phen
yl)-1,3,4-oxa-diazole.
AB - In the title compound C19H11F3N2O2, the oxa-diazole ring and the naphthalene ring
system are approximately planar (r.m.s. deviations of 0.001 and 0.020 A,
respectively) and the oxa-diazole ring makes dihedral angles of 13.11 (1) and
7.59 (1) degrees with the naphthalene ring system and the tri-fluoro-phenyl
ring, respectively. In the crystal, C-H?N hydrogen bonds link mol-ecules into
chains along the a-axis direction, while C-H?F contacts form additional chains
along the ac diagonal. These contacts generate sheets of mol-ecules approximately
parallel to the (011) plane.
PMID- 25844243
TI - Crystal structure of 5,7-diphenyl-4,7-di-hydro-tetra-zolo[1,5-a]pyrimidine.
AB - In the title mol-ecule, C16H13N5, the plane of the tetra-zole ring forms dihedral
angles of 16.37 (7) and 76.59 (7) degrees with the two phenyl rings. The
dihedral angle between the phenyl rings is 68.05 (6) degrees . The pyrimidine
ring is in a flattened boat conformation. In the crystal, mol-ecules are linked
by pairs of N-H?N hydrogen bonds, forming inversion dimers.
PMID- 25844244
TI - Crystal structure of 2-methyl-piperazine-1,4-diium bis-(hydrogen maleate).
AB - In the title salt, C5H14N2 (2+).2C4H3O4 (-), the asymmetric unit contains two
independent 2-methyl-piperazinium dications, which comprise a racemic pair, and
four hydrogen maleate monoanions. In the roughly planar hydrogen maleate anions,
intra-molecular O-H?O hydrogen bonds generate S(7) rings. In the crystal, the
four independent anions are linked to the 2-methyl-piperazinium cations through N
H?O hydrogen bonds, forming two-dimensional layered structures lying parallel to
(001).
PMID- 25844245
TI - Crystal structure of ethyl (2S,2'R)-1'-benzyl-3-oxo-3H-di-spiro-[1-benzo-thio
phene-2,3'-pyrrolidine-2',11''-indeno[1,2-b]quinoxaline]-4'-carboxyl-ate.
AB - In the title compound, C35H27N3O3S, the spiro-linked five-membered rings both
adopt twisted conformations. The pyrrolidine ring makes dihedral angles of 80.5
(1) and 77.4 (9) degrees with the benzo-thio-phene ring system and the
quinoxaline ring system, respectively. The S atom and C=O unit of the benzo-thio
phene ring system are disordered over two opposite orientations in a 0.768
(4):0.232 (4) ratio. The atoms of the ethyl side chain are disordered over two
sets of sites in a 0.680 (16):0.320 (16) ratio. In the crystal, mol-ecules are
linked by C-H?O, C-H?N and pi-pi inter-actions [shortest centroid-centroid
distance = 3.4145 (19) A], resulting in a three-dimensional network.
PMID- 25844246
TI - Crystal structure of 4,6-di-amino-2-(methyl-sulfan-yl)pyridine-3-carbo-nitrile.
AB - The title pyrimidine derivative, C7H8N4S, is essentially planar, with a maximum
deviation of 0.029 (2) A from the mean plane of the non-H atoms. In the crystal,
mol-ecules are linked by an inter-molecular bifurcated N-H?N hydrogen bond
between the cyano N atom and the two amino groups, an N-H?N hydrogen bond between
the two amino groups and a weak C-H?pi inter-action, forming a three-dimensional
network.
PMID- 25844247
TI - Crystal structure of S-hexyl (E)-3-(4-methoxy-benzyl-idene)di-thio-carbazate.
AB - In the title compound, C15H22N2OS2, the di-thio-carbazate group adopts an EE
conformation with respect to the C=N bond of the benzyl-idene moiety. The hexyl
side chain adopts an extended conformation and the C-S-C-C torsion angle is
93.36 (13) degrees . In the crystal, inversion dimers linked by pairs of N-H?S
hydrogen bonds generate R 2 (2)(8) loops.
PMID- 25844248
TI - Crystal structure of 1-{1-[2-(phenyl-selan-yl)phen-yl]-1H-1,2,3-triazol-4
yl}cyclo-hexan-1-ol.
AB - Two independent mol-ecules, A and B, comprise the asymmetric unit of the title
compound, C20H21N3OSe. While the benzene ring directly bound to the central
triazole ring is inclined to the same extent in both mol-ecules [dihedral angles
= 40.41 (12) (mol-ecule A) and 44.14 (12) degrees (B)], greater differences are
apparent in the dihedral angles between the Se-bound rings, i.e. 74.28 (12) (mol
ecule A) and 89.91 (11) degrees (B). Close intra-molecular Se?N inter-actions of
2.9311 (18) (mol-ecule A) and 2.9482 (18) A (B) are noted. In the crystal, supra
molecular chains along the a axis are formed via O-H?N hydrogen bonding. These
are connected into layers via C-H?O and C-H?N inter-actions; these stack along
(01-1) without directional inter-molecular inter-actions between them.
PMID- 25844249
TI - Crystal structure of 1-{2-[(2-meth-oxy-phen-yl)selan-yl]phen-yl}-4-phenyl-1H
1,2,3-triazole.
AB - In the title compound, C21H17N3OSe, the dihedral angles between the central five
membered ring and the C- and N-bound rings are 17.89 (10) and 42.35 (10) degrees
, respectively, indicating the mol-ecule is twisted. The dihedral angle between
the Se-bound rings is 85.36 (10) degrees . A close intra-molecular Se?O contact
of 2.8507 (13) A is noted. In the crystal, C-H?O, C-H?N and C-H?pi inter-actions
lead to the formation of supra-molecular layers parallel to (011); these stack
with no specific inter-molecular inter-actions between them.
PMID- 25844250
TI - Crystal structure of 4-phenyl-1-{2-[(2,4,6-tri-methyl-phen-yl)selan-yl]phen-yl}
1H-1,2,3-triazole.
AB - In the title compound, C23H21N3Se, the C-bound phenyl ring is almost coplanar
with the central five-membered ring [dihedral angle = 2.84 (10) degrees ], but
the N-bound benzene ring is inclined [dihedral angle = 47.52 (10) degrees ]. The
dihedral angle between the Se-bound rings is 69.24 (9) degrees . An intra
molecular Se?N inter-action of 3.0248 (15) A is noted. In the crystal, C-H?pi
inter-actions connect mol-ecules into double layers that stack along the a axis
with no directional inter-actions between them.
PMID- 25844251
TI - Crystal structure of ethyl 6-methyl-2-oxo-4-(3,4,5-tri-meth-oxy-phen-yl)-1,2,3,4
tetra-hydro-pyrimidine-5-carboxyl-ate.
AB - In the title compound, C17H22N2O6, the di-hydro-pyrimidine ring adopts a
flattened boat conformation. The dihedral angle between the benzene ring and the
mean plane of the di-hydro-pyrimidine ring is 75.25 (6) degrees . In the crystal,
mol-ecules are linked via pairs of N-H?O hydrogen bonds, forming inversion dimers
with an R 2 (2)(8) ring motif which are linked through N-H?O and weak C-H?O
hydrogen bonds. These, together with pi-pi ring inter-actions [centroid-centroid
distance = 3.7965 (10) A], give an overall three-dimensional structure.
PMID- 25844252
TI - Crystal structure of (E)-2-[1-(1,3-benzodioxol-5-yl)ethyl-idene]-N-ethyl-hydra
zine-1-carbo-thio-amide.
AB - In the title compound, C12H15N3O2S, the 1,3-benzdioxole fragment is nearly planar
[the maximum deviation being 0.0515 (14) A], the N-N-C(=S)-N fragment is also
nearly planar [the maximum deviation being 0.0480 (10) A], and the dihedral angle
between their mean planes is 23.49 (10) degrees . In the crystal, mol-ecules are
linked by pairs of N-H?S hydrogen bonds, forming inversion dimers. The dimers are
stacked along the a axis with neighbouring columns having the same direction;
however, the mol-ecules show different orientations leading to a centrosymmetric
arrangement. In the crystal, the methyl-ene group of the ethyl substituent and
the terminal methyl H atoms are disordered over two sets of sites and were
refined using a split model with an occupancy ratio of 0.5:0.5.
PMID- 25844253
TI - Crystal structure of 1-meth-oxy-pyrene.
AB - The title compound, C17H12O, crystallized with three independent mol-ecules (A, B
and C) in the asymmetric unit. In the crystal, the three independent mol-ecules
are linked by pi-pi inter-actions [centroid-centroid distances = 3.551 (3)-3.977
(2) A], which lead to the formation of trimers. Between the trimers there are a
number of C-H?pi inter-actions generating a laminar arrangement parallel to
(010). The meth-oxy-methyl group in mol-ecule A is disordered over two sets of
sites, with an occupancy ratio of 0.56 (9):0.44 (9).
PMID- 25844254
TI - Crystal structure of diethyl 2-amino-6-[(thio-phen-3-yl)ethyn-yl]azulene-1,3-di
carboxyl-ate.
AB - The title compound, C22H19NO4S, has an almost planar geometry supported by intra
molecular N-H?O and C-H?O hydrogen bonds. The thio-phene ring is inclined to the
azulene ring by 4.85 (16) degrees , while the eth-oxy-carbonyl groups are
inclined to the azulene ring by 7.0 (2) and 5.7 (2) degrees . In the crystal, mol
ecules are linked by pairs of N-H?O hydrogen bonds, forming inversion dimers with
an R 2 (2)(12) ring motif. The dimers are linked via C-H?pi inter-actions,
forming sheets parallel to (10-1).
PMID- 25844255
TI - Crystal structure of 2-benzamido-N-(2,2-di-eth-oxy-eth-yl)benzamide.
AB - In the title compound, C20H24N2O4, both peptide bonds adopt a trans configuration
with respect to the -N-H and -C=O groups. The dihedral angle between the aromatic
rings is 53.58 (4) degrees . The mol-ecular conformation is stabilized by an
intra-molecular N-H?O hydrogen bond. The crystal packing is characterized by
zigzag chains of N-H?O hydrogen-bonded mol-ecules running along the b-axis
direction.
PMID- 25844256
TI - Crystal structure of the tripeptide N-(benzyl-oxycarbon-yl)glycylglycyl-l
norvaline.
AB - The title tripeptide, C17H23N3O6, contains a nonproteinogenic C-terminal amino
acid residue, norvaline, which is an isomer of the amino acid valine. Norvaline,
unlike valine, has an unbranched side chain. The mol-ecule has a Gly-Gly segment
which adopts an extended conformation. The norvaline residue also adopts an
extended backbone conformation while its side chain has a g (+) t conformation.
In the crystal lattice, N-H?O and O-H?O hydrogen bonds stabilize the packing. Mol
ecules translated along the crystallographic a axis associate through an N-H?O
hydrogen bond. The remaining three hydrogen bonds are between mol-ecules related
by a 2 1 screw axis.
PMID- 25844257
TI - The Mississippi Delta Cardiovascular Health Examination Survey: Study Design and
Methods.
AB - Assessment of cardiovascular disease (CVD) morbidity and mortality in subnational
areas is limited. A model for regional CVD surveillance is needed, particularly
among vulnerable populations underrepresented in current monitoring systems. The
Mississippi Delta Cardiovascular Health Examination Survey (CHES) is a population
based, cross-sectional study on a representative sample of adults living in the
18-county Mississippi Delta region, a rural, impoverished area with high rates of
poor health outcomes and marked health disparities. The primary objectives of
Delta CHES are to (1) determine the prevalence and distribution of CVD and CVD
risk factors using self-reported and directly measured health metrics and (2) to
assess environmental perceptions and existing policies that support or deter
healthy choices. An address-based sampling frame is used for household
enumeration and participant recruitment and an in-home data collection model is
used to collect survey data, anthropometric measures, and blood samples from
participants. Data from all sources will be merged into one analytic dataset and
sample weights developed to ensure data are representative of the Mississippi
Delta region adult population. Information gathered will be used to assess the
burden of CVD and guide the development, implementation, and evaluation of
cardiovascular health promotion and risk factor control strategies.
PMID- 25844258
TI - Resurgence of mumps in Korea.
AB - Routine vaccination against mumps has markedly reduced its incidence. However,
the incidence of mumps continuously has increased since 2007. In 2013, a large
mumps epidemic occurred in Korea, and this epidemic is still an ongoing problem.
This epidemic occurred primarily in school settings and affected vaccinated
adolescents, predominantly male students. The recent resurgence of mumps is
caused by multiple factors: suboptimal effectiveness of the current mumps
vaccines, use of the Rubini strain vaccine, waning immunity in the absence of
natural boosting due to the marked reduction in the mumps incidence, genotype
mismatch between the vaccine and circulating mumps virus strains, and
environmental conditions that foster intense exposures. Containment of mumps
outbreaks is challenging because the sensitivity of diagnostic tests is low among
vaccinees and control measures are less efficient because of the inherent nature
of the mumps virus. Despite the suboptimal vaccine effectiveness in outbreak
settings, maintaining the high vaccine coverage is an important strategy to
prevent mumps outbreaks, given that the routine use of mumps vaccines has
substantially reduced the incidence of mumps and its complications as compared
with that in the pre-vaccine era. In order to control the current mumps epidemic
and prevent further outbreaks, we need to better understand the dynamics of mumps
among vaccinated populations and the changing epidemiology in Korea. Concerted
efforts should be made to systematically monitor the immunization status of the
Korean population and to improve diagnosis efficiency. Furthermore, more
effective mumps vaccines need to be developed in the future.
PMID- 25844259
TI - A common immunopathogenesis mechanism for infectious diseases: the protein
homeostasis-system hypothesis.
AB - It was once believed that host cell injury in various infectious diseases is
caused solely by pathogens themselves; however, it is now known that host immune
reactions to the substances from the infectious agents and/or from the injured
host cells by infectious insults are also involved. All biological phenomena in
living organisms, including biochemical, physiological and pathological
processes, are performed by the proteins that have various sizes and shapes,
which in turn are controlled by an interacting network within the living
organisms. The author proposes that this network is controlled by the protein
homeostasis system (PHS), and that the immune system is one part of the PHS of
the host. Each immune cell in the host may recognize and respond to substances,
including pathogenic proteins (PPs) that are toxic to target cells of the host,
in ways that depend on the size and property of the PPs. Every infectious disease
has its own set of toxic substances, including PPs, associated with disease
onset, and the PPs and the corresponding immune cells may be responsible for the
inflammatory processes that develop in those infectious diseases.
PMID- 25844260
TI - In vitro Comparison of Anti-Biofilm Effects against Carbapenem-Resistant
Acinetobacter baumannii: Imipenem, Colistin, Tigecycline, Rifampicin and
Combinations.
AB - BACKGROUND: Multi-drug resistant (MDR) Acinetobacter baumannii has emerged as one
of the most important nosocomial pathogens. In addition to the diverse resistance
mechanisms, some A. baumannii strains are known to have biofilm-producing
capacity, thereby decreasing antibiotic effectiveness. MATERIALS AND METHODS:
This study was designed to assess biofilm-producing capacity of three different
MDR A. baumannii strains with diverse resistance mechanisms (OXA-51, IMP-1 and
VIM-2 type beta-lactamases), and intended to compare the effect of each
antibiotic regimen (rifampicin, colistin, imipenem, tigecycline, rifampicin
imipenem and rifampicin-colistin) on mature A. baumannii biofilms using in vitro
polystyrene plate biofilm assay. RESULTS: Among three MDR A. baumannii strains,
only VIM-2 strain produced strong biofilm compared to the controls (optical
density, 8.04 +/- 2.16 vs. 0.49 +/- 0.26). Regarding VIM-2 strains, none of
imipenem, colistin and rifampicin reduced biofilm formation alone at MIC of each
antibiotic agent (inhibition of biofilm synthesis, less than 30%). In comparison,
tigecyclin (0.76 +/- 0.23), imipenem-rifampicin (1.07 +/- 0.31) and colistin
rifampicin (1.47 +/- 0.54) showed a significant inhibition of biofilm synthesis
compared to the positive controls at 48 hours after incubation (P<0.01).
Tigecycline inhibited biofilm formation even at the one fourth level of MIC (1.17
+/- 0.21). Likewise, both imipenem and colistin were also effective even with the
reduced concentrations when those were combined with rifampicin. Such biofilm
inhibiting effects with those antibiotic regimens sustained up to 96 hours after
incubation. CONCLUSION: Tigecycline, imipenem-rifampicin and colistin-rifampicin
would be effective for the prevention or reduction of biofilm formation caused by
A. baumannii strains.
PMID- 25844261
TI - Characteristics of Metallo-beta-Lactamase-Producing Pseudomonas aeruginosa in
Korea.
AB - BACKGROUND: The aim of this study was to investigate the molecular
epidemiological characteristics of metallo-beta-lactamase (MBL)-producing
Pseudomonas aeruginosa clinical isolates in Korea. MATERIALS AND METHODS: Three
hundred and twenty nine P. aeruginosa clinical isolates were collected from 23
general hospitals in Korea from March to June 2014. Species were identified by
matrix-assited laser desorption/ionization-time of flight and 16S rRNA
sequencing. Antimicrobial susceptibility was determined by disk diffusion
methods. Further, minimum inhibitory concentrations of carbapenems were
determined by Etest. Polymerase chain reaction and sequencing were performed to
identify genes encoding MBLs. Multi-locus sequence typing and pulsed-field gel
electrophoresis were performed to determine epidemiological characteristics of
MBL-producing P. aeruginosa isolates. RESULTS: Of the 329 isolates, 229 (69.6%)
were susceptible to the carbapenems tested, including imipenem and meropenem;
while 100 (30.4%) were non-susceptible to more than one of the carbapenems. Genes
encoding imipenemase-6 (IMP-6) and Verona imipenemase-2 (VIM-2) MBLs were
identified in 21 (6.4%) isolates (n = 17 and 4, respectively). All MBL-producing
isolates showed multi-drug resistant phenotype, and a majority (n = 19) of the
isolates were identified as sequence type 235 (ST235). The remaining isolates (n
= 2) were identified as ST309 and ST463. CONCLUSION: P. aeruginosa ST235 might
play an important role in dissemination of MBL genes in Korea.
PMID- 25844262
TI - Influenza and Pneumococcal Vaccine Coverage Rates among Patients Admitted to a
Teaching Hospital in South Korea.
AB - BACKGROUND: Influenza and pneumococcal vaccinations can reduce morbidity and
mortality especially in the elderly and patients with chronic medical disease.
The purpose of this study was to estimate vaccination coverage of these
populations in a hospital setting. MATERIALS AND METHODS: We conducted a cross
sectional, descriptive study involving adult patients admitted to a 1,000-bed
teaching hospital on April 15, 2013. We ascertained the information on whether
the patient had received influenza vaccination within a year prior to admission
or pneumococcal vaccination by interviewing each patient. RESULTS: A total of 491
eligible patients aged >=50 years or with chronic medical illnesses were
analyzed. The overall vaccination rate for influenza was 57.2%, and that of
pneumococcus was 17.6% among the vaccine-eligible subjects.
Influenza/pneumococcal vaccination rates of patients by disease were 62.8%/17.2%
for diabetes, 53.3%/15.6% for malignancy, 67.6%/23.5% for chronic pulmonary
disease, 66.7%/15.3% for chronic cardiovascular disease, 68.7%/26.9% for chronic
renal disease, and 51.2%/18.6% for chronic hepatic disease. Young adult patients
with chronic medical conditions were consistently less likely to receive
influenza and pneumococcal vaccines irrespective of the underlying disease.
CONCLUSION: The influenza and pneumococcal vaccine coverage rates among
hospitalized patients were low in South Korea. This was especially the case for
young adult patients with chronic medical illnesses.
PMID- 25844263
TI - Fatal Breakthrough Mucormycosis in an Acute Myelogenous Leukemia Patient while on
Posaconazole Prophylaxis.
AB - Posaconazole is a new oral triazole with broad-spectrum antifungal activity.
Posaconazole has also shown a significant advantage of preventing invasive fungal
infection compared to fluconazole or itraconazole in patients with prolonged
neutropenia. Indeed, posaconazole has been commonly used for antifungal
prophylaxis in patients undergoing remission induction chemotherapy for acute
myelogenous leukemia or myelodysplastic syndrome. We experienced a case of fatal
mucormycosis despite posaconazole prophylaxis. To our knowledge, this is the
first reported case of fatal breakthrough mucormycosis in a patient receiving
posaconazole prophylaxis during remission induction chemotherapy in Korea. This
case demonstrated that breakthrough fungal infection can occurs in patients
receiving posaconazole prophylaxis because of its limited activity against some
mucorales.
PMID- 25844264
TI - The first imported case infected with chikungunya virus in Korea.
AB - Chikungunya is caused by an arbovirus transmitted by Aedes mosquito vector. With
the increase of habitat of mosquito by global warming and frequent international
travel and interchange, chikungunya reemerged and showed global distribution
recently. Until now there has not been reported any case infected with
chikungunya virus in Korea. A 23-year-old man has been the Republic of the
Philippines for 1 week, and visited our emergency center due to fever and back
pain. Chikungunya viral infection was diagnosed by specific IgM for chickungunya
virus by enzyme-linked immunosorbent assayin Korea Centers for Disease Control
and Prevention. His clinical course was self limited. We introduce the first
imported case infected with chikungunya virus in Korea.
PMID- 25844265
TI - Disseminated gonococcal infection presenting as bacteremia and liver abscesses in
a healthy adult.
AB - Herein, we describe a bacteremia caused by Neisseria gonorrhoeae that presented
as liver abscesses. The patient had no risk factors for disseminated gonococcal
infection. Periodic fever, skin rashes, and papules were present and the results
of an abdominal computed tomography scan indicated the presence of small liver
abscesses. The results of blood culture and 16S rRNA sequencing of the bacterial
isolates confirmed the presence of N. gonorrhoeae. The patient improved with
antibiotic therapy.
PMID- 25844266
TI - A Case of Paenibacillus pasadenensis Bacteremia in a Patient with Acute
Respiratory Distress Syndrome after Microsurgical Clipping.
AB - We report the first case of bacteremia by a novel Paenibacillus species,
Paenibacillus pasadenensis, from a 55-year-old male patient with acute
respiratory distress syndrome, following a microsurgical clipping procedure of a
ruptured intracranial aneurysm. The bacterium was identified using 16S rRNA gene
sequencing analysis, which was applied because current conventional methods
employed in the clinical microbiology laboratory proved unsuccessful. Since this
bacterium was first identified in 2006 and has never been reported elsewhere, we
believe this report can provide practitioners with useful insight on the
pathogenicity of this species.
PMID- 25844267
TI - Revised adult immunization guideline recommended by the korean society of
infectious diseases, 2014.
PMID- 25844268
TI - A multifaceted trophic cascade in a detritus-based system: density-, trait-, or
processing-chain-mediated effects?
AB - We investigated three pathways by which predators on an intermediate trophic
level may produce a trophic cascade in detritus-based systems. Predators may
increase lower trophic levels (bacteria) by reducing density of bacteriovores, by
altering behavior of bacteriovores, and by processing living bacteriovores into
carcasses, feces, and dissolved nutrients that are substrates for bacteria. We
tested these pathways in laboratory experiments with mosquitoes in water-filled
containers. Larval Toxorhynchites rutilus prey on larval Aedes triseriatus, which
feed on bacteria. Using containers stocked with oak leaf infusion as a bacterial
substrate, we compared bacterial productivity at 7 and 14 days for: prey alone;
prey with a predator; and prey with predation cues but no predator. Controls
contained no larvae, either with predation cues or without cues. Predation cues
in the control treatment increased bacterial abundance at 7 days, but this effect
waned by 14 days. Aedes triseriatus larvae reduced bacterial abundance
significantly at 14 days. Predator cues and real predation both eliminated the
negative effect of A. triseriatus on bacterial abundance. Predation cues reduced
survivorship of A. triseriatus larvae at 14 days, however this effect was smaller
than the effect of real predation. We further tested effects of residues from
predation as cues or as detritus in a second experiment in which A. triseriatus
were killed at similar rates by: real predators; mechanical damage without the
predator and carcasses left as detritus; or mechanical damage and carcasses
removed. No prey larvae were killed in controls. Bacterial productivity was
greater with real predation than in all other treatments and greater when prey
larvae were killed or killed and removed, than in controls. Thus we find evidence
that all three pathways contribute to the trophic cascade from T. rutilus to
bacteria in tree hole systems.
PMID- 25844269
TI - HIV/AIDS - Related Knowledge, Attitudes, and Sexual Practices among Migrant Wives
in Rural Anhui Province, China.
AB - BACKGROUND: Migrant wives have been increasing in some poor rural regions of
China and they may bridge HIV transmission across regions. This study aimed to
assess HIV/AIDS-related knowledge, attitudes and sexual practices among this
population in rural Anhui Province, China. METHODS: A cross-sectional survey was
conducted with questionnaire of HIV/AIDS-related knowledge, attitudes, and sexual
practices between June 2011 and May 2012. A total of 730 migrant wives and 207
local women were enrolled in this study. Unpaired T-test, Chi-square was utilized
to compare the difference of HIV/AIDS knowledge, attitudes and sexual practices
between migrant wives and local women. RESULTS: Around 80% of the migrant wives
were from Yunnan, Guizhou, or Sichuan Provinces. The main sources of HIV/AIDS
information were TV/radio, posters, and newspapers/periodicals. HIV/AIDS
knowledge level among migrant wives was significantly lower than that among local
women (e.g. 47.1% vs 57.0% (p<0.001) answered "Yes" for the question "Can an
apparently healthy person be HIV-infected?"), and stigma and prejudice towards
HIV/AIDS among migrant wives were more common than those among local women (e.g.
73.2% vs 65.7% (p=0.006) answered "No" for the question "If a shopkeeper or food
seller had the HIV, would you buy food from them?"). Compared to local women,
migrant wives were more likely to have ever had sex during menstruation (6.8% vs
3.4%, p=0.065) and extramarital sex (17.5% vs 10.1%, p=0.01), and were less
likely to consistently use condoms with their husbands (45.8% vs 57.5%, p<0.001)
or extramarital sex partners (48.8% vs 58.95, p<0.001). CONCLUSIONS: Migrant
wives in rural China had a low HIV/AIDS knowledge level and high prevalence of
stigma and prejudice and risky sexual behaviors. Local HIV/AIDS prevention
programs should target this neglected population.
PMID- 25844271
TI - Interparental Boundary Problems, Parent-Adolescent Hostility, and Adolescent
Parent Hostility: A Family Process Model for Adolescent Aggression Problems.
AB - This study tests interparental boundary problems (IBPs), parent hostility with
adolescents, and adolescent hostility with parents within a reciprocal influence
model and tests each as risk factors for adolescent aggression problems.
Prospective, longitudinal analyses were conducted with multi-informant data from
768 adolescents and their families, from 6th to 9th grade. Guided by spillover
and social learning perspectives, our findings suggest that IBPs have a robust,
negative influence on both parent and adolescent hostility. In turn, adolescent
hostility was the best predictor of global adolescent aggression problems. Two
indirect effects were found that link IBPs and adolescent aggression problems;
however, findings indicate that adolescent hostile behavior in the family is the
key risk indicator for adolescents' later aggression problems. Model invariance
tests revealed that this model was not different for boys and girls, or for
adolescents in families with two biological parents and youth in families with
two caregivers (e.g. stepparent families).
PMID- 25844270
TI - Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats.
AB - OBJECTIVE: Progesterone (P4) plays a central role in women's health. Synthetic
progestins are used clinically in hormone replacement therapy (HRT), oral
contraceptives, and for the treatment of endometriosis and infertility.
Unfortunately, synthetic progestins are associated with side effects, including
cardiovascular disease and breast cancer. Botanical dietary supplements are
widely consumed for the alleviation of a variety of gynecological issues, but
very few studies have characterized natural compounds in terms of their ability
to bind to and activate progesterone receptors (PR). Kaempferol is a flavonoid
that functions as a non-steroidal selective progesterone receptor modulator
(SPRM) in vitro. This study investigated the molecular and physiological effects
of kaempferol in the ovariectomized rat uteri. METHODS: Since genistein is a
phytoestrogen that was previously demonstrated to increase uterine weight and
proliferation, the ability of kaempferol to block genistein action in the uterus
was investigated. Analyses of proliferation, steroid receptor expression, and
induction of well-established PR-regulated targets Areg and Hand2 were completed
using histological analysis and qPCR gene induction experiments. In addition,
kaempferol in silico binding analysis was completed for PR. The activation of
estrogen and androgen receptor signalling was determined in vitro. RESULTS:
Molecular docking analysis confirmed that kaempferol adopts poses that are
consistent with occupying the ligand-binding pocket of PRA. Kaempferol induced
expression of PR regulated transcriptional targets in the ovariectomized rat
uteri, including Hand2 and Areg. Consistent with progesterone-l ke activity,
kaempferol attenuated genistein-induced uterine luminal epithelial proliferation
without increasing uterine weight. Kaempferol signalled without down regulating
PR expression in vitro and in vivo and without activating estrogen and androgen
receptors. CONCLUSION: Taken together, these data suggest that kaempferol is a
unique natural PR modulator that activates PR signaling in vitro and in vivo
without triggering PR degradation.
PMID- 25844272
TI - Carbohydrate-Based Polymers for Immune Modulation.
AB - Carbohydrates play prominent roles in immune surveillance and response to
infection. Multivalency, molecular weight control, and molecular architecture
control are properties that polymer science is well suited to address. Each of
these properties has been demonstrated to impact the biological interaction of
carbohydrate-bearing chains with their binding partners. This viewpoint
highlights synthetic advances and potential applications of carbohydrate-based
polymers for immune modulation. It also offers future directions in polymer
science necessary for carbohydrate polymers to fulfill their potential as immune
modulators.
PMID- 25844273
TI - Gene-diet interactions and their impact on colorectal cancer risk.
AB - A number of studies have evaluated the role of gene-diet interaction in the
etiology of colorectal cancer (CRC). Historically, these studies focused on
established dietary risk factors and genes involved in their metabolism. However,
results from these candidate gene studies were inconsistent, possibly due to
multiple testing and publication bias. In recent years, genome-wide association
studies have identified a number of CRC susceptibility loci, and subsequent meta
analyses have observed limited evidence that diet may modify the risk associated
with these susceptibility loci. Statistical techniques have been recently
developed to evaluate the presence of interaction across the entire genome;
results from these genome-wide studies have demonstrated limited evidence of
interaction and have failed to replicate results from candidate gene studies and
those using established susceptibility loci. However, larger sample sizes are
likely needed to elucidate modest or weak interaction in genome-wide studies of
gene-diet interaction.
PMID- 25844274
TI - Retroviral DNA Transposition: Themes and Variations.
AB - Retroviruses and LTR retrotransposons are transposable elements that encapsidate
the RNAs that are intermediates in the transposition of DNA copies of their
genomes (proviruses), from one cell (or one locus) to another. Mechanistic
similarities in DNA transposase enzymes and retroviral/retrotransposon integrases
underscore the close evolutionary relationship among these elements. The
retroviruses are very ancient infectious agents, presumed to have evolved from
Ty3/Gypsy LTR retrotransposons (1), and DNA copies of their sequences can be
found embedded in the genomes of most, if not all, members of the tree of life.
All retroviruses share a specific gene arrangement and similar replication
strategies. However, given their ancestries and occupation of diverse
evolutionary niches, it should not be surprising that unique sequences have been
acquired in some retroviral genomes and that the details of the mechanism by
which their transposition is accomplished can vary. While every step in the
retrovirus lifecycle is, in some sense, relevant to transposition, this Chapter
focuses mainly on the early phase of retroviral replication, during which viral
DNA is synthesized and integrated into its host genome. Some of the initial
studies that set the stage for current understanding are highlighted, as well as
more recent findings obtained through use of an ever-expanding technological
toolbox including genomics, proteomics, and siRNA screening. Persistence in the
area of structural biology has provided new insight into conserved mechanisms as
well as variations in detail among retroviruses, which can also be instructive.
PMID- 25844277
TI - The formation of a large summertime Saharan dust plume: Convective and synoptic
scale analysis.
AB - Haboobs are dust storms produced by the spreading of evaporatively cooled air
from thunderstorms over dusty surfaces and are a major dust uplift process in the
Sahara. In this study observations, reanalysis, and a high-resolution simulation
using the Weather Research and Forecasting model are used to analyze the
multiscale dynamics which produced a long-lived (over 2 days) Saharan mesoscale
convective system (MCS) and an unusually large haboob in June 2010. An upper
level trough and wave on the subtropical jet 5 days prior to MCS initiation
produce a precipitating tropical cloud plume associated with a disruption of the
Saharan heat low and moistening of the central Sahara. The restrengthening
Saharan heat low and a Mediterranean cold surge produce a convergent region over
the Hoggar and Air Mountains, where small convective systems help further
increase boundary layer moisture. Emerging from this region the MCS has
intermittent triggering of new cells, but later favorable deep layer shear
produces a mesoscale convective complex. The unusually large size of the
resulting dust plume (over 1000 km long) is linked to the longevity and vigor of
the MCS, an enhanced pressure gradient due to lee cyclogenesis near the Atlas
Mountains, and shallow precipitating clouds along the northern edge of the cold
pool. Dust uplift processes identified are (1) strong winds near the cold pool
front, (2) enhanced nocturnal low-level jet within the aged cold pool, and (3) a
bore formed by the cold pool front on the nocturnal boundary layer.
PMID- 25844276
TI - Systematic, theoretically-grounded development and feasibility testing of an
innovative, preventive web-based game for children exposed to acute trauma.
AB - BACKGROUND: Millions of children are affected by acute medical events annually,
creating need for resources to promote recovery. While web-based interventions
promise wide reach and low cost for users, development can be time- and cost
intensive. A systematic approach to intervention development can help to minimize
costs and increase likelihood of effectiveness. Using a systematic approach, our
team integrated evidence on the etiology of traumatic stress, an explicit program
theory, and a user-centered design process to intervention development.
OBJECTIVE: To describe evidence and the program theory model applied to the
Coping Coach intervention and present pilot data evaluating intervention
feasibility and acceptability. METHOD: Informed by empirical evidence on
traumatic stress prevention, an overarching program theory model was articulated
to delineate pathways from a) specific intervention content to b) program targets
and proximal outcomes to c) key longer-term health outcomes. Systematic user
testing with children ages 8-12 (N = 42) exposed to an acute medical event and
their parents was conducted throughout intervention development. RESULTS:
Functionality challenges in early prototypes necessitated revisions. Child
engagement was positive throughout revisions to the Coping Coach intervention.
Final pilot-testing demonstrated promising feasibility and high user-engagement
and satisfaction. CONCLUSION: Applying a systematic approach to the development
of Coping Coach led to the creation of a functional intervention that is accepted
by children and parents. Development of new e-health interventions may benefit
from a similar approach. Future research should evaluate the efficacy of Coping
Coach in achieving targeted outcomes of reduced trauma symptoms and improved
health-related quality of life.
PMID- 25844275
TI - Site-specific DNA Inversion by Serine Recombinases.
AB - Reversible site-specific DNA inversion reactions are widely distributed in
bacteria and their viruses. They control a range of biological reactions that
most often involve alterations of molecules on the surface of cells or phage.
These programmed DNA rearrangements usually occur at a low frequency, thereby
preadapting a small subset of the population to a change in environmental
conditions, or in the case of phages, an expanded host range. A dedicated
recombinase, sometimes with the aid of additional regulatory or DNA architectural
proteins, catalyzes the inversion of DNA. RecA or other components of the general
recombination-repair machinery are not involved. This chapter discusses site
specific DNA inversion reactions mediated by the serine recombinase family of
enzymes and focuses on the extensively studied serine DNA invertases that are
stringently controlled by the Fis-bound enhancer regulatory system. The first
section summarizes biological features and general properties of inversion
reactions by the Fis/enhancer-dependent serine invertases and the recently
described serine DNA invertases in Bacteroides. Mechanistic studies of reactions
catalyzed by the Hin and Gin invertases are then discussed in more depth,
particularly with regards to recent advances in our understanding of the function
of the Fis/enhancer regulatory system, the assembly of the active recombination
complex (invertasome) containing the Fis/enhancer, and the process of DNA strand
exchange by rotation of synapsed subunit pairs within the invertasome. The role
of DNA topological forces that function in concert with the Fis/enhancer
controlling element in specifying the overwhelming bias for DNA inversion over
deletion and intermolecular recombination is emphasized.
PMID- 25844278
TI - Probabilistic detection of volcanic ash using a Bayesian approach.
AB - : Airborne volcanic ash can pose a hazard to aviation, agriculture, and both
human and animal health. It is therefore important that ash clouds are monitored
both day and night, even when they travel far from their source. Infrared
satellite data provide perhaps the only means of doing this, and since the hugely
expensive ash crisis that followed the 2010 Eyjafjalljokull eruption, much
research has been carried out into techniques for discriminating ash in such data
and for deriving key properties. Such techniques are generally specific to data
from particular sensors, and most approaches result in a binary classification of
pixels into "ash" and "ash free" classes with no indication of the classification
certainty for individual pixels. Furthermore, almost all operational methods rely
on expert-set thresholds to determine what constitutes "ash" and can therefore be
criticized for being subjective and dependent on expertise that may not remain
with an institution. Very few existing methods exploit available contemporaneous
atmospheric data to inform the detection, despite the sensitivity of most
techniques to atmospheric parameters. The Bayesian method proposed here does
exploit such data and gives a probabilistic, physically based classification. We
provide an example of the method's implementation for a scene containing both
land and sea observations, and a large area of desert dust (often misidentified
as ash by other methods). The technique has already been successfully applied to
other detection problems in remote sensing, and this work shows that it will be a
useful and effective tool for ash detection. KEY POINTS: Presentation of a
probabilistic volcanic ash detection schemeMethod for calculation of probability
density function for ash observationsDemonstration of a remote sensing technique
for monitoring volcanic ash hazards.
PMID- 25844279
TI - The importance of reviewers.
PMID- 25844280
TI - Microdiskectomy and translaminar approach: minimal invasiveness and flavum
ligament preservation.
AB - Study Design Retrospective study. Objective The interlaminar approach represents
the standard procedure for the surgical treatment of lumbar disk herniation
(LDH). In the case of disk herniations in the "hidden zone," it could be
necessary to perform laminotomies or laminectomies and partial or total
facetectomies to remove the herniated fragment, thus leading to iatrogenic
instability. The objective of the study is to evaluate the translaminar approach,
in terms of the results, safety, and efficacy compared with the standard
approach. Methods Since February 2010, 38 patients (26 men and 12 women; mean age
50.9 years, range 31 to 78 years) with LDH and migration into the hidden zone
underwent a microdiskectomy by the translaminar approach. Using a micro-diamond
dust-coated burr, a translaminar hole (8 +/- 2 mm) was made, with subsequent
exposure of the involved root and removal of the fragment. A clinical follow-up
was performed at months 1, 3, 6, and 12 using the visual analog scale and the
Oswestry Disability Index. All patients were evaluated according to the Spangfort
score. Postoperative radiographic evaluations were done at 1, 6, and 12 months
(dynamic radiographic studies done at 6 and 12 months). Results In over 60% of
cases, L4-L5 was the involved disk. The visualization of the roots was
successfully achieved through a translaminar approach. No laminotomies,
laminectomies, or partial or total facetectomies were performed. The flavum
ligament was always spared. A severe intraoperative bleeding episode occurred in
5% of the cases, due to involvement of the epidural veins, but it did not result
in prolonged operative time (mean duration 60 +/- 10 minutes). The patients
showed a gradual resolution of the back pain and a progressive resolution of the
radicular pain and the neurologic deficits. No sign of radiographic instability
was documented during the follow-up. No infections, dural tears, or spinal cord
injuries occurred. No revision surgery was performed. Conclusion The translaminar
approach is the only tissue-sparing technique viable in case of cranially
migrated LDH encroaching on the exiting nerve root in the preforaminal zones, for
the levels above L2-L3, and in the preforaminal and foraminal zones, for the
levels below L3-L4 (L5-S1 included, if a total microdiskectomy is not necessary).
The possibility to spare the flavum ligament is one of the main advantages of
this technique. According to our experience, the translaminar approach is an
effective and safe alternative minimally invasive surgical option.
PMID- 25844281
TI - Computer-aided surgery does not increase the accuracy of dorsal pedicle screw
placement in the thoracic and lumbar spine: a retrospective analysis of 2,003
pedicle screws in a level I trauma center.
AB - Study Design A retrospective analysis of a prospective database. Objective Meta
analyses suggest that computer-assisted systems can increase the accuracy of
pedicle screw placement for dorsal spinal fusion procedures. The results of
further meta-analyses report that in the thoracic spine, both the methods have
comparable placement accuracy. These studies are limited due to an abundance of
screw classification systems. The aim of this study was to assess the placement
accuracy and potentially influencing factors of three-dimensionally navigated
versus conventionally inserted pedicle screws. Methods This was a retrospective
analysis of a prospective database at a level I trauma center of pedicle screw
placement (computer-navigated versus traditionally placed) for dorsal spinal
stabilizations. The cases spanned a 5.5-year study period (January 1, 2005, to
June 30, 2010). The perforations of the pedicle were differentiated in three
grades based on the postoperative computed tomography. Results The overall
placement accuracy was 86% in the conventional group versus 79% in the computer
navigated group (grade 0). The computer-navigated procedures were superior in the
lumbar spine and the conventional procedures were superior in the thoracic spine,
but both failed to be of statistical significance. The level of experience of the
performing surgeon and the patient's body mass index did not influence the
placement accuracy. The only significant influence was the spinal segment: the
higher the spinal level where the fusion was performed, the more likely the screw
was displaced. Conclusions The computer-navigated and conventional methods are
both safe procedures to place transpedicular screws at the traumatized thoracic
and lumbar spine. At the moment, three-dimensionally based navigation does not
significantly increase the placement accuracy.
PMID- 25844282
TI - Does Transforaminal Lumbar Interbody Fusion Have Advantages over Posterolateral
Lumbar Fusion for Degenerative Spondylolisthesis?
AB - Study Design Retrospective cohort study. Objective To compare the clinical and
radiographic outcomes of transforaminal lumbar interbody fusion (TLIF) and
posterolateral lumbar fusion (PLF) in the treatment of degenerative
spondylolisthesis. Methods This study compared 24 patients undergoing TLIF and 32
patients undergoing PLF with instrumentation. The clinical outcomes were assessed
by visual analog scale (VAS) for low back pain and leg pain, physical component
summary (PCS) of the 12-item Short-Form Health Survey, and the Oswestry
Disability Index (ODI). Radiographic parameters included slippage of the
vertebra, local disk lordosis, the anterior and posterior disk height, lumbar
lordosis, and pelvic parameters. Results The improvement of VAS of leg pain was
significantly greater in TLIF than in PLF unilaterally (3.4 versus 1.0; p =
0.02). The improvement of VAS of low back pain was significantly greater in TLIF
than in PLF (3.8 versus 2.2; p = 0.02). However, there was no significant
difference in improvement of ODI or PCS between TLIF and PLF. Reduction of
slippage and the postoperative disk height was significantly greater in TLIF than
in PLF. There was no significant difference in local disk lordosis, lumbar
lordosis, or pelvic parameters. The fusion rate was 96% in TLIF and 84% in PLF (p
= 0.3). There was no significant difference in fusion rate, estimated blood loss,
adjacent segmental degeneration, or complication rate. Conclusions TLIF was
superior to PLF in reduction of slippage and restoring disk height and might
provide better improvement of leg pain. However, the health-related outcomes were
not significantly different between the two procedures.
PMID- 25844283
TI - Transfer of the brachialis to the anterior interosseous nerve as a treatment
strategy for cervical spinal cord injury: technical note.
AB - Study Design Technical report. Objective To provide a technical description of
the transfer of the brachialis to the anterior interosseous nerve (AIN) for the
treatment of tetraplegia after a cervical spinal cord injury (SCI). Methods In
this technical report, the authors present a case illustration of an ideal
surgical candidate for a brachialis-to-AIN transfer: a 21-year-old patient with a
complete C7 spinal cord injury and failure of any hand motor recovery. The
authors provide detailed description including images and video showing how to
perform the brachialis-to-AIN transfer. Results The brachialis nerve and AIN
fascicles can be successfully isolated using visual inspection and motor mapping.
Then, careful dissection and microsurgical coaptation can be used for a
successful anterior interosseous reinnervation. Conclusion The nerve transfer
techniques for reinnervation have been described predominantly for the treatment
of brachial plexus injuries. The majority of the nerve transfer techniques have
focused on the upper brachial plexus or distal nerves of the lower brachial
plexus. More recently, nerve transfers have reemerged as a potential
reinnervation strategy for select patients with cervical SCI. The brachialis-to
AIN transfer technique offers a potential means for restoration of intrinsic hand
function in patients with SCI.
PMID- 25844284
TI - Age-related surgical outcomes of laminoplasty for cervical spondylotic
myelopathy.
AB - Study Design Retrospective clinical study. Objective To investigate the age
related surgical outcomes of laminoplasty. Methods One hundred patients who
underwent an en bloc laminoplasty for cervical spondylotic myelopathy from 2004
to 2008 and were followed for at least 1 year were included in this study. The
clinical outcomes were assessed with the Japanese Orthopaedic Association (JOA)
score. Acquired points (postoperative JOA score minus preoperative JOA score)
were also calculated. To investigate the age-related effect for laminoplasty, two
analyses were conducted: (1) the correlation between age and clinical outcome;
and (2) the clinical outcomes by decade. Patients were divided into four groups
according to their age at the time of operation as follows: group 50s, 50 to 59
years old; group 60s, 60 to 69 years; group 70s, 70 to 79 years; and group 80s,
80 to 89 years. The pre- and postoperative JOA scores, acquired points,
preoperative comorbidities, and postoperative complications were then compared
among the groups. Results Significant correlations were detected between age and
JOA scores at the preoperative (p = 0.03), postoperative maximum (p < 0.0001),
and final assessments (p < 0.0001). An age-related decline of JOA scores was
observed over all periods. The analysis by decades showed the same results. On
the other hand, the significant differences were not found for acquired points
over all periods by either method. The preoperative comorbidities of hypertension
and diabetes mellitus increased with age. Delirium was more common
postoperatively in elderly patients. Conclusions Although an age-related decline
of JOA scores was found over all periods, there were no severe sequelae and no
differences in the acquired points that were age-related.
PMID- 25844285
TI - Adverse effect of trauma on neurologic recovery for patients with cervical
ossification of the posterior longitudinal ligament.
AB - Study Design Retrospective study. Objective Minor trauma, even from a simple
fall, can often cause cervical myelopathy, necessitating surgery in elderly
patients who may be unaware of their posterior longitudinal ligament ossification
(OPLL). The aim of this study is to determine the influence of trauma on the
neurologic course in patients who have undergone surgery for cervical OPLL.
Methods Patients who underwent surgery due to OPLL were divided by trauma history
and compared (34 in the trauma group; 70 in the nontrauma group). Results Ground
falls were the most common type of trauma (20 patients, low-energy injuries), but
23 patients developed new symptoms after a trauma. Although the symptom duration
(17.68 months) was shorter, the Japanese Orthopedic Association (JOA) score and
the Nurick scale showed lower values in the trauma group. Trauma histories led
patients to earlier hospital visits. Initial JOA scores were associated with a
good recovery status upon the last follow-up in both the groups. The narrowest
diameter of the spinal canal showed different radiologic parameters: 5.78 mm in
the trauma group and 6.52 mm in the nontrauma group. Conclusion Minor trauma can
cause the unexpected development of new symptoms in patients unaware of cervical
OPLL. Patients with a history of trauma had lower initial JOA scores and showed a
narrower spinal canal compared with a nontrauma group. The initial JOA scores
were correlated with a good recovery status upon the last follow-up.
PMID- 25844286
TI - Diskectomy during Pregnancy: Case Report and Review of the Literature.
AB - Study Design Case report. Objective The purpose of this report is to discuss the
management of a disk herniation during pregnancy and the indication and
particularities of surgery in this situation. Methods We describe a case of
diskectomy performed in a 35-year-old woman at 18 weeks of gestation. After 4
weeks of trying to manage the disk herniation with rest and medications without
success, the muscle strength of the L5 right root decreased to grade 4, and the
patient was not responding to intravenous analgesia. After discussion with the
patient and family, a decision was made to perform the diskectomy. Results After
surgery, the patient's pain lessened, and the Lasegue test became negative. Two
weeks after the procedure, the patient's muscle strength was normal. In the 40th
week of pregnancy, the patient gave birth without any complications. Conclusion
When necessary, diskectomy can be indicated and performed during pregnancy.
However, appropriate precautions must be taken. Awareness of these precautions is
important for the success of the procedure and for the well-being of the mother
and the newborn.
PMID- 25844287
TI - Minimally invasive treatment of a painful osteolytic lumbar lesion secondary to
epithelioid hemangioendothelioma.
AB - Study Design Case report. Objective Multifocal epithelioid hemangioendothelioma
(EHE) of the spine is a rare disorder. We describe a novel, multimodal treatment
of a painful osteolytic lumbar lesion secondary to EHE. The minimally invasive
treatment results in an excellent patient outcome with decreased morbidity
compared to traditional techniques. Methods A previously healthy young adult
presented with a painful osteolytic lesion at the L2 vertebrae. Imaging revealed
multifocal spinal lesions consistent with a history of EHE. Core needle biopsy
confirmed the diagnosis. Preoperative cryoablation of L2 was followed by a staged
surgery, which included a partial L2 corpectomy, tumor resection, bone grafting,
and vertebral reconstruction using a minimally invasive technique. This treatment
was followed by prolonged therapy with interferon and bisphosphonate. Results At
3.5 years' follow-up, the patient has maintained his vertebral body height, has
not required a fusion, and has had no recurrence of disease. Conclusion
Multimodal treatment consisting of tumor cryoablation, partial corpectomy,
allograft reconstruction of the vertebrae, and adjuvant interferon and
bisphosphonate can result in good outcomes for well-contained EHE tumors of the
spine.
PMID- 25844288
TI - Corpectomy with adjacent-level kyphoplasty to treat metastatic lung cancer in
three contiguous cervical vertebrae causing focal neurologic compromise.
AB - Study Design Case report. Objectives Decompression of metastatic spinal cord
compression has been shown to improve quality of life and prolong ambulation in
patients undergoing palliative treatment. We report a case of metastatic cervical
myelopathy treated with a combined approach using corpectomy and stabilization
together with balloon kyphoplasty to allow adequate decompression and immediate
stability in a patient with significant destruction of adjacent vertebral bodies.
Methods The cervical spine was approached anteriorly and decompressed with a C7
corpectomy. Subsequent stability was achieved with insertion of a trabecular
metal cage. Balloon kyphoplasty was used to treat lytic lesions within the
posterior body of the adjacent vertebrae for pain relief and increased stability.
Additional stability was achieved through the application of an anterior plate.
Results Full limited decompression and stabilization were successfully achieved.
The patient had no further neurologic deterioration and made modest improvements
that allowed a return to independent ambulation. Conclusion This limited approach
may be an option for patients with metastatic spinal cord compression, lytic
destruction of adjacent vertebral bodies, and limited life expectancy.
PMID- 25844289
TI - Thoracic Spondylodiscitis Caused by Methicillin-resistant Staphylococcus aureus
as a Superinfection of Pulmonary Tuberculous Granuloma in an Immunocompetent
Patient: A Case Report.
AB - Study Design Case report. Objective To describe a very rare case of an
immunocompetent man who underwent surgery for thoracic spondylodiscitis caused by
methicillin-resistant Staphylococcus aureus (MRSA) that developed as a
superinfection of a pulmonary tuberculous granuloma. Methods Posterior
decompression and pedicle screw vertebral fixation were followed by T5-T6
anterior somatotomy with implant of an expandable mesh and lateral plating as
symptoms worsened. During the anterior approach, an atypical resection of the
left lower lobe was also performed. Results A tuberculous granuloma was detected
on histology. Ziehl-Neelsen stain confirmed the diagnosis. Culture also detected
MRSA. Conclusions Early medical management is the first choice for
spondylodiscitis to eradicate the infection and alleviate pain. Immobilization of
the affected spine segments can protect the patient from vertebral collapse and
from the appearance of neurologic deficits. Surgery is suggested if there are
compressive effects on the spinal cord, spinal epidural abscess, vertebral
collapse, and deformity. We decided to remove the abscess and to restore the
anterior column using an anterior approach. Moreover, in this case, an anterior
approach allowed us to identify the etiology of the lesion and to determine the
best chemotherapy regimen.
PMID- 25844290
TI - A Meta-Analysis of the Clinical and Fusion Results following Treatment of
Symptomatic Cervical Pseudarthrosis.
AB - Study Design Systematic literature review and meta-analysis. Objective This study
is a meta-analysis assessing the fusion rate and the clinical outcomes of
cervical pseudarthrosis treated with either a posterior or a revision anterior
approach. Methods A literature search of PubMed, Cochrane, and Embase was
performed. Variables of interest included fusion rate and clinical success. The
effect size based on logit event rate was calculated from the pooled results. The
studies were weighted by the inverse of the variance, which included both within-
and between-study error. The confidence intervals were reported at 95%.
Heterogeneity was assessed using the Q statistic and I (2), where I (2) is the
estimate of the percentage of error due to between-study variation. Results
Sixteen studies reported fusion outcomes; 10 studies reported anterior and/or
posterior results. The pooled fusion success was 86.4% in the anterior group and
97.1% in the posterior group (p = 0.028). The anterior group demonstrated
significant heterogeneity with Q value of 34.2 and I (2) value of 73.7%; no
heterogeneity was seen in the posterior group. The clinical outcomes were
reported in 10 studies, with eight reporting results of anterior and posterior
approaches. The pooled clinical success rate was 77.0% for anterior and 71.7% for
posterior (p = 0.55) approaches. There was significant heterogeneity in both
groups (I (2) 16.1; 19.2). Conclusions Symptomatic cervical pseudarthrosis can be
effectively managed with either an anterior or a posterior approach. The
posterior approach demonstrates a significantly greater fusion rate compared with
the anterior approach, though the clinical outcome does not differ between the
two groups.
PMID- 25844291
TI - Fundamentals of clinical outcomes assessment for spinal disorders: study designs,
methodologies, and analyses.
AB - Study Design A broad narrative review. Objective Management of spinal disorders
is continuously evolving, with new technologies being constantly developed.
Regardless, assessment of patient outcomes is key in understanding the safety and
efficacy of various therapeutic interventions. As such, evidence-based spine care
is an essential component to the armamentarium of the spine specialist in an
effort to critically analyze the reported literature and execute studies in an
effort to improve patient care and change clinical practice. The following
article, part one of a two-part series, is meant to bring attention to the pros
and cons of various study designs, their methodological issues, as well as
statistical considerations. Methods An extensive review of the peer-reviewed
literature was performed, irrespective of language of publication, addressing
study designs and their methodologies as well as statistical concepts. Results
Numerous articles and concepts addressing study designs and their methodological
considerations as well as statistical analytical concepts have been reported.
Their applications in the context of spine-related conditions and disorders were
noted. Conclusion Understanding the fundamental principles of study designs and
their methodological considerations as well as statistical analyses can further
advance and improve future spine-related research.
PMID- 25844292
TI - Intraoperative Vagus Nerve Monitoring: A Transnasal Technique during Skull Base
Surgery.
AB - Objectives Intraoperative vagus nerve monitoring during skull base surgery has
been reported with the use of an oral nerve monitoring endotracheal tube.
However, the intraoral presence of an endotracheal tube can limit exposure by its
location in the operative field during transfacial approaches and by limiting
superior mobilization of the mandible during transcervical approaches. We
describe a transnasal vagus nerve monitoring technique. Design and Participants
Ten patients underwent open skull base surgery. Surgical approaches included
transcervical (five), transfacial/maxillary swing (three), and double mandibular
osteotomy (two). The vagus nerve was identified, stimulated, and monitored in all
cases. Main Outcome Measures Intraoperative nerve stimulation, pre- and
postoperative vagus nerve function through the use of flexible laryngoscopy in
conjunction with assessment of subjective symptoms of hoarseness, voice change,
and swallowing difficulty. Results Three patients had extensive involvement of
the nerve by tumor with complete postoperative nerve deficit, one patient had a
transient deficit following dissection of tumor off of nerve with resolution, and
the remaining patients had nerve preservation. One patient experienced minor
epistaxis during monitor tube placement that was managed conservatively.
Conclusions Transnasal vagal nerve monitoring is a simple method that allows for
intraoperative monitoring during nerve preservation surgery without limiting
surgical exposure.
PMID- 25844293
TI - Technical nuances of autologous pericranium harvesting for dural closure in
Chiari malformation surgery.
AB - Duraplasty is a step commonly used for the treatment of Chiari I malformation
after foramen magnum decompression. A variety of dural substitutes are currently
available for dural closure to minimize the complications related to
cerebrospinal fluid (CSF). We describe a technique of harvesting occipital
pericranium for duraplasty associated with preservation of a wide cuff of muscle
at the superior nuchal line that allows anatomical muscle closure at the end of
the procedure. Five symptomatic patients with Chiari I malformation and one
patient with syringomyelia-Chiari I complex were operated on with this technique.
The indications to perform a duraplasty were accidental arachnoid breaching in
three patients during an extra-arachnoidal approach and arachnoidal dissection
due to intraoperative findings of arachnoid pathology in the remaining three
patients. The overall morbidity of this technique was nil. In all patients the
postoperative magnetic resonance imaging scan demonstrated significant expansion
of the cisterna magna with no evidence of pseudomeningocele. Duraplasty with
autologous pericranium and standardized closure of soft tissues seem promising in
reducing the CSF-related complications during Chiari surgery.
PMID- 25844294
TI - Incidence and survival patterns of sinonasal undifferentiated carcinoma in the
United States.
AB - Objective To determine trends in sinonasal undifferentiated carcinoma (SNUC)
survival patterns in the United States. Design Retrospective review of national
database. Participants All cases of SNUC in the National Cancer Institute's
Surveillance Epidemiology and End Results program from 1973 to 2010 were
examined. Main Outcome Measures Age-adjusted incidence and survival rates were
calculated and stratified by demographic information and treatment modality.
Cohort analysis was performed to analyze survival patterns over time. Results A
total of 318 SNUC cases were identified. Age-adjusted incidence rate (IR) was
0.02 per 100,000. Incidence was greater in males (IR: 0.03) than females (IR:
0.01; p = 0.03). Overall 5- and 10-year relative survival rate was 34.9% and
31.3%, respectively. Overall median survival was 22.1 months. Median survival
following surgery combined with radiation was 41.9 months. Five-year relative
survival rate following surgery, radiation, or surgery combined with radiation
was 38.7%, 36.0%, and 39.1%, respectively. Median survival from 1973-1986 and
1987-2010 was 14.5 and 23.5 months, respectively. Conclusions This study provides
new data regarding survival patterns of SNUC in the United States, confirming
survival benefit with surgery and radiation as well as identifying a trend toward
improved survival in recent decades.
PMID- 25844295
TI - Early Conquest of the Rock: Julius Lempert's Life and the Complete Apicectomy
Technique for the Treatment of Suppurative Petrous Apicitis.
AB - Julius Lempert (1891-1968) was one of the most revolutionary and innovative neuro
otologists of the 20th century. He had a remarkable role in advancing the field
of otolaryngology to its modern shape and form, especially through his
groundbreaking introduction of the fenestration procedure for the treatment of
otosclerosis. Although he is highly celebrated by many neuro-otologists for his
contributions to our surgical and anatomical understanding of the petrous bone,
he is not well known to the neurosurgical community. In this article, we give a
detailed account of Dr. Lempert's life and discuss his invaluable contribution to
skull base petrous bone anatomy and surgery through his pioneering work on the
complete apicectomy for the treatment of suppurative petrous apicitis.
PMID- 25844296
TI - Immediate single-stage reconstruction of complex frontofaciobasal injuries: part
I.
AB - Objective To determine if immediate (within 6 hours of adequate resuscitation)
single-stage repair of complex craniofacial injuries could be accomplished with
acceptable morbidity and mortality taking into consideration the cosmetic
appearance of the patient. Patients and Methods A total of 26 patients (19 men, 7
women) ranging in age from 8 to 58 years with Glasgow Coma Scale scores of 5 to
15 all had a combined single-stage repair of their complex craniofacial injuries
within 6 hours of their admission. After initial assessment and adequate
resuscitation, they were evaluated with three-dimensional computed tomography of
the face and head. Coronal skin flap was used for maximum exposure for frontal
sinus exenteration as well as dural repair, cortical debridement, calvarial
reconstruction, and titanium mesh placement. Results Neurosurgical outcome at
both the early and late evaluations was judged as good in 22 of 26 patients
(85%), moderate in 3 of 26 (11%), and poor in 1 of the 26 (3.8%). Cosmetic
surgical outcome at the early evaluation showed 17 of 26 (65%) to be excellent, 4
of 26 (15.5%) to be good, 4 patients (15.5%) to be fair, and 1 patient (3.8%) to
be poor. At the late reevaluation, the fair had improved to good with an
additional reconstructive procedure, and the poor had improved to fair with
another surgery. There was no calvarial osteomyelitis, graft resorption, or
intracranial abscess. Complications included three patients (11%): one (3.8%) had
tension pneumocephaly and meningitis, one (3.8%) had delayed cerebrospinal fluid
leak with recurrent attacks of meningitis, and one had a maxillary sinus
infection (3.8%) secondary to front maxillary fistula. Conclusion The immediate
single-stage repair of complex craniofacial injuries can be performed with
acceptable results, a decreased need for reoperation, and improved cosmetic and
functional outcomes.
PMID- 25844297
TI - C-shaped Incision for Far-Lateral Suboccipital Approach: Anatomical Study and
Clinical Correlation.
AB - Background The standard incision for far-lateral suboccipital approaches has been
the classic "reverse hockey stick." Although that incision provides ample
exposure, concern has been raised that excessive muscle dissection and skin
elevation might lead to accumulation of cerebrospinal fluid (CSF) under the flap
with increased risk of CSF leak. We hypothesize that the C-shaped incision can
minimize the amount of muscle dissection and provide optimal exposure and
surgical outcomes. Objective To describe the anatomical dissection for the C
shaped incision and clinical application of the C-shaped incision for the far
lateral approach. Methods A retrospective analysis of all the patients operated
on at our center using this approach for the treatment of aneurysm of the
posterior inferior cerebellar artery (PICA) from 2005 to 2011. Results of
clinical and operative outcome are evaluated. Surgical techniques are described
in detail. Cadaveric dissections using the C-shaped incision were performed to
assess the exposure of the far-lateral suboccipital area. Results Eleven
consecutive patients who had undergone this procedure were selected. All patients
underwent clipping of PICA aneurysms. Nine patients (82%) presented with ruptured
aneurysms and subarachnoid hemorrhage. All of them underwent suboccipital
craniectomy and C1 laminectomy. The dura mater was closed in a watertight fashion
in 10 patients (91%). No CSF leak or pseudomeningocele were reported. In nine SAH
patients, two (22%) had postoperative dysphagia and required long-term
percutaneous endoscopic gastrostomy tube placement. One patient (11%) had chronic
respiratory failure and required a tracheostomy. Three patients (33%) developed
hydrocephalus and required a ventriculoperitoneal shunt. Conclusions The C-shaped
incision is a valid alternative to the classic reverse hockey-stick incision to
gain exposure for far-lateral craniotomies. Knowing the anatomy and dissection
techniques can provide an easy and safe route to address anterior lateral cranial
cervical lesions. Our results suggest the C-shaped incision is reliable in
preventing CSF leak and the formation of pseudomeningocele.
PMID- 25844298
TI - To preserve or not to preserve the orbit in paranasal sinus neoplasms: a meta
analysis.
AB - Context The effect on survival of orbital evisceration on patients with paranasal
sinus neoplasms has not been well established. Objective To review systematically
the available literature concerning survival in patients who undergo surgery for
paranasal sinus neoplasm with and without preservation of the eye. Data Source A
retrospective meta-analysis of English and non-English articles using Medline and
the Cochrane database. Eligibility Criteria Studies analyzing 5-year survival
rates in patients who had orbital evisceration compared with orbital preservation
for the treatment of paranasal sinus neoplasms were included in the final
analysis. Data Extraction Independent review by two authors using predefined data
fields. Data Synthesis A meta-analysis of four articles involving 443 patients
was performed using the DerSimonian-Laird random-effects method. Results Our
analysis revealed a total effect size of 0.964 in favor of preservation of the
eye; however, these results are not robust, having a true effect size anywhere
from 0.785 to 1.142 with a 95% confidence interval. Limitations Only
retrospective observational studies were included because a prospective
randomized study cannot be performed in this population. Conclusion Our study
supports the notion that in select patients preservation of the eye may yield a
different outcome when compared with orbital evisceration.
PMID- 25844299
TI - Junctional Internal Carotid Artery Aneurysms: The Schrodinger's Cat of Vascular
Neurosurgery.
AB - Objectives Despite advances in neuroimaging, it is not always definitive whether
a paraclinoid aneurysm is intradural or entirely extradural. We illustrate the
potential use of surgical exploration in these aneurysms that we refer to as
"junctional" aneurysms. Methods Retrospective review of eight patients with
unruptured aneurysms who underwent a planned surgical exploration of a junctional
aneurysm. Results Of the eight patients, three underwent exploration of the
aneurysm during surgery for a different aneurysm. All three of these were found
to be extradural. Five patients underwent a craniotomy for the exclusive purpose
of clarifying the location of the aneurysm. Two of these cases were found to be
intradural and were clipped. Two cases were found to be extradural. In one
patient, the initially extradural aneurysm was converted into an intradural
aneurysm during removal of the anterior clinoid process, necessitating surgical
clipping. One transient third nerve palsy was observed. Discussion Until further
progress in neuroimaging allows clinicians to determine unequivocally the exact
anatomical location of a paraclinoid aneurysm, we advocate the use of the term
junctional aneurysm to reflect the clinical uncertainty inherent in management
decisions made regarding these aneurysms. We have illustrated a strategy of
surgical exploration in select patients.
PMID- 25844300
TI - Facial Nerve Outcome after Vestibular Schwannoma Resection: A Comparative Meta
Analysis of Endoscopic versus Open Retrosigmoid Approach.
AB - The minimal access retrosigmoid endoscopic approach to vestibular schwannoma (VS)
resection has been used with promising results. However, it has not been compared
with the standard open approach in the literature. We performed a meta-analysis
review for all articles describing both approaches for VS from 1996 to 2011. We
found 1861 articles. After review and discussion, we narrowed our study to 25
articles, 4 endoscopic and 21 open. The total number of patients was 3026 for
open and 790 for endoscopic. The mean tumor sizes in the open and endoscopic
series were 2.5 cm and 2.7 cm, respectively. Good facial nerve outcome was
achieved in 67% of the open series patients and in 94% of the endoscopic series
patients. Other outcomes in the open and endoscopic series were the following:
gross total resection, 91% versus 97%; functional hearing, 22.6% versus 46%;
wound infection, 1.3% versus 2.6%; and recurrence, 5.4% versus 2.2%. We
acknowledge the limitations of our study, but we can state that the endoscopic
approach is not inferior to the standard open approach. In expert hands the
endoscopic approach can offer as good a result as the open, with potential
benefits such as less pain and a shorter length of stay in the hospital. There is
a need for more controlled studies for a definitive comparison.
PMID- 25844301
TI - The evolution of endoscopic approaches to the lateral cavernous sinus.
PMID- 25844302
TI - In reference to "extended inferior turbinate flap for endoscopic reconstruction
of skull base defects".
PMID- 25844303
TI - Who will benefit from antidepressants in the acute treatment of bipolar
depression? A reanalysis of the STEP-BD study by Sachs et al. 2007, using Q
learning.
AB - BACKGROUND: There is substantial uncertainty regarding the efficacy of
antidepressants in the treatment of bipolar disorders. METHODS: Traditional
randomized controlled trials and statistical methods are not designed to discover
if, when, and to whom an intervention should be applied; thus, other
methodological approaches are needed that allow for the practice of personalized,
evidence-based medicine with patients with bipolar depression. RESULTS: Dynamic
treatment regimes operationalize clinical decision-making as a sequence of
decision rules, one per stage of clinical intervention, that map patient
information to a recommended treatment. Using data from the acute depression
randomized care (RAD) pathway of the Systematic Treatment Enhancement Program for
Bipolar Disorder (STEP-BD) study, we estimate an optimal dynamic treatment regime
via Q-learning. CONCLUSIONS: The estimated optimal treatment regime presents some
evidence that patients in the RAD pathway of STEP-BD who experienced a
(hypo)manic episode before the depressive episode may do better to forgo adding
an antidepressant to a mandatory mood stabilizer.
PMID- 25844304
TI - Extended Matrix and Inverse Matrix Methods Utilizing Internal Validation Data
When Both Disease and Exposure Status Are Misclassified.
AB - The problem of misclassification is common in epidemiological and clinical
research. In some cases, misclassification may be incurred when measuring both
exposure and outcome variables. It is well known that validity of analytic
results (e.g. point and confidence interval estimates for odds ratios of
interest) can be forfeited when no correction effort is made. Therefore, valid
and accessible methods with which to deal with these issues remain in high
demand. Here, we elucidate extensions of well-studied methods in order to
facilitate misclassification adjustment when a binary outcome and binary exposure
variable are both subject to misclassification. By formulating generalizations of
assumptions underlying well-studied "matrix" and "inverse matrix" methods into
the framework of maximum likelihood, our approach allows the flexible modeling of
a richer set of misclassification mechanisms when adequate internal validation
data are available. The value of our extensions and a strong case for the
internal validation design are demonstrated by means of simulations and analysis
of bacterial vaginosis and trichomoniasis data from the HIV Epidemiology Research
Study.
PMID- 25844305
TI - Sensory Phenomena in Tourette Syndrome: Their Role in Symptom Formation and
Treatment.
AB - The primary symptoms of Tourette Syndrome (TS) are motor and vocal tics, but
increasingly, researchers have examined the role of sensory phenomena in
biobehavioral models of the disorder. These sensory phenomena involve tic-related
premonitory urge sensations as well as potential abnormalities in the perceptual
and behavioral experiences associated with external sensory input. As such,
dysfunctional sensorimotor integration might represent a key facet of TS
pathology. The current paper reviews the literature on sensory phenomena in tic
disorders and highlights possible connections to TS symptoms and directions for
future research.
PMID- 25844306
TI - Anatomical likelihood estimation meta-analysis of grey and white matter anomalies
in autism spectrum disorders.
AB - Autism spectrum disorders (ASD) are characterized by impairments in social
communication and restrictive, repetitive behaviors. While behavioral symptoms
are well-documented, investigations into the neurobiological underpinnings of ASD
have not resulted in firm biomarkers. Variability in findings across structural
neuroimaging studies has contributed to difficulty in reliably characterizing the
brain morphology of individuals with ASD. These inconsistencies may also arise
from the heterogeneity of ASD, and wider age-range of participants included in
MRI studies and in previous meta-analyses. To address this, the current study
used coordinate-based anatomical likelihood estimation (ALE) analysis of 21 voxel
based morphometry (VBM) studies examining high-functioning individuals with ASD,
resulting in a meta-analysis of 1055 participants (506 ASD, and 549 typically
developing individuals). Results consisted of grey, white, and global differences
in cortical matter between the groups. Modeled anatomical maps consisting of
concentration, thickness, and volume metrics of grey and white matter revealed
clusters suggesting age-related decreases in grey and white matter in parietal
and inferior temporal regions of the brain in ASD, and age-related increases in
grey matter in frontal and anterior-temporal regions. White matter alterations
included fiber tracts thought to play key roles in information processing and
sensory integration. Many current theories of pathobiology ASD suggest that the
brains of individuals with ASD may have less-functional long-range (anterior-to
posterior) connections. Our findings of decreased cortical matter in parietal
temporal and occipital regions, and thickening in frontal cortices in older
adults with ASD may entail altered cortical anatomy, and neurodevelopmental
adaptations.
PMID- 25844307
TI - Neural correlates of cerebellar-mediated timing during finger tapping in children
with fetal alcohol spectrum disorders.
AB - OBJECTIVES: Classical eyeblink conditioning (EBC), an elemental form of learning,
is among the most sensitive indicators of fetal alcohol spectrum disorders. The
cerebellum plays a key role in maintaining timed movements with millisecond
accuracy required for EBC. Functional MRI (fMRI) was used to identify cerebellar
regions that mediate timing in healthy controls and the degree to which these
areas are also recruited in children with prenatal alcohol exposure. EXPERIMENTAL
DESIGN: fMRI data were acquired during an auditory rhythmic/non-rhythmic finger
tapping task. We present results for 17 children with fetal alcohol syndrome
(FAS) or partial FAS, 17 heavily exposed (HE) nonsyndromal children and 16 non-
or minimally exposed controls. PRINCIPAL OBSERVATIONS: Controls showed greater
cerebellar blood oxygen level dependent (BOLD) activation in right crus I, vermis
IV-VI, and right lobule VI during rhythmic than non-rhythmic finger tapping. The
alcohol-exposed children showed smaller activation increases during rhythmic
tapping in right crus I than the control children and the most severely affected
children with either FAS or PFAS showed smaller increases in vermis IV-V. Higher
levels of maternal alcohol intake per occasion during pregnancy were associated
with reduced activation increases during rhythmic tapping in all four regions
associated with rhythmic tapping in controls. CONCLUSIONS: The four cerebellar
areas activated by the controls more during rhythmic than non-rhythmic tapping
have been implicated in the production of timed responses in several previous
studies. These data provide evidence linking binge-like drinking during pregnancy
to poorer function in cerebellar regions involved in timing and somatosensory
processing needed for complex tasks requiring precise timing.
PMID- 25844308
TI - The temporal unfolding of face processing in social anxiety disorder--a MEG
study.
AB - The current study is the first to use magnetoencephalography (MEG) to examine how
individuals with social anxiety disorder (SAD) process emotional facial
expressions (EFEs). We expected that, compared to healthy controls (HCs),
participants with SAD will show an early (<200 ms post-stimulus) over-activation
in the insula and the fusiform gyrus (FG, associated with the N170/M170
component), and later (>200 ms post-stimulus) over-activation in the dorsolateral
prefrontal cortex (DLPFC). Individuals with SAD (n = 12) and healthy controls
(HCs, n = 12) were presented with photographs of facial displays during MEG
recording. As compared to the HC group, the SAD group showed a reduced M170
(right FG under-activation around 130-200 ms); early reduced activation in the
right insula, and lower insular sensitivity to the type of EFE displayed. In
addition, the SAD group showed a late over-activation in the right DLPFC. This
unique EFE processing pattern in SAD suggests an early under-activation of
cortical areas, possibly related to reduced emphasis on high spatial frequency
information and greater early emphasis on low spatial frequency information. The
late DLPFC over-activation in the SAD group may correlate to failures of
cognitive control in this disorder. The importance of a temporal perspective for
the understanding of facial processing in psychopathology is underlined.
PMID- 25844309
TI - Regional differences in fiber tractography predict neurodevelopmental outcomes in
neonates with infantile Krabbe disease.
AB - BACKGROUND: Krabbe disease is a fatal neurodegenerative disease caused by rapid
demyelination of the central and peripheral nervous systems. The only available
treatment, unrelated umbilical cord blood transplantation, is effective only if
performed before clinical symptoms appear. Phenotypic expressions of disease
causing mutations vary widely, but genotype-phenotype relationships are unclear.
Therefore, we evaluated diffusion tensor imaging (DTI) tractography with
volumetric analysis as a biomarker of early white matter changes and functional
disability in presymptomatic infants. METHODS: We obtained DTI and structural
scans of newborns with early-infantile Krabbe disease (n = 9) diagnosed by family
history or newborn screening. We compared white matter fiber tract properties to
those of normal controls (n = 336) and assessed the ability of tract-based
properties to predict longitudinal development in four functional domains
(cognitive, fine motor, gross motor, adaptive behavior) after treatment with
unrelated umbilical cord blood transplantation. We also assessed the relationship
between the standard evaluation (modified Loes score) and DTI results, and the
volumetric differences between the Krabbe subjects and normal controls. FINDINGS:
Reductions in fractional anisotropy were significant in the corticospinal tract
in the Krabbe patients compared to controls, which strongly correlated with motor
and cognitive outcomes after transplantation. Significant regional differences
were observed in the splenium and uncinate fasciculus in Krabbe patients and
these differences correlated only with cognitive outcomes. Regional brain volumes
of Krabbe patients were slightly larger than controls. Loes scores did not
correlate with DTI results. INTERPRETATION: Neonatal microstructural
abnormalities correlate with neurodevelopmental treatment outcomes in patients
treated for infantile Krabbe disease. DTI with quantitative tractography is an
excellent biomarker for evaluating infants with Krabbe disease identified through
newborn screening.
PMID- 25844310
TI - Age related-changes in the neural basis of self-generation in verbal paired
associate learning.
AB - Verbal information is better retained when it is self-generated rather than when
it is received passively. The application of self-generation procedures has been
found to improve memory in healthy elderly and in individuals with impaired
cognition. Overall, the available studies support the notion that active
participation in verbal encoding engages memory mechanisms that supplement those
used during passive observation. Thus, the objective of this study was to
investigate the age-related changes in the neural mechanisms involved in the
encoding of paired-associates using a self-generation method that has been shown
to improve memory performance across the lifespan. Subjects were 113 healthy
right-handed adults (Edinburgh Handedness Inventory >50; 67 females) ages 18-76,
native speakers of English with no history of neurological or psychiatric
disorders. Subjects underwent fMRI at 3 T while performing didactic learning
("read") or self-generation learning ("generate") of 30 word pairs per condition.
After fMRI, recognition memory for the second word in each pair was evaluated
outside of the scanner. On the post-fMRI testing more "generate" words were
correctly recognized than "read" words (p < 0.001) with older adults recognizing
the "generated" words less accurately (p < 0.05). Independent component analysis
of fMRI data identified task-related brain networks. Several components were
positively correlated with the task reflecting multiple cognitive processes
involved in self-generated encoding; other components correlated negatively with
the task, including components of the default-mode network. Overall, memory
performance on generated words decreased with age, but the benefit from self
generation remained consistently significant across ages. Independent component
analysis of the neuroimaging data revealed an extensive set of components engaged
in self-generation learning compared with didactic learning, and identified areas
that were associated with age-related changes independent of performance.
PMID- 25844311
TI - Multimodal MRI and cognitive function in patients with breast cancer prior to
adjuvant treatment--the role of fatigue.
AB - An increasing body of literature indicates that chemotherapy (ChT) for breast
cancer (BC) is associated with adverse effects on the brain. Recent research
suggests that cognitive and brain function in patients with BC may already be
compromised before the start of chemotherapy. This is the first study combining
neuropsychological testing, patient-reported outcomes, and multimodal magnetic
resonance imaging (MRI) to examine pretreatment cognition and various aspects of
brain function and structure in a large sample. Thirty-two patients with BC
scheduled to receive ChT (pre-ChT+), 33 patients with BC not indicated to undergo
ChT (pre-ChT-), and 38 no-cancer controls (NCs) were included. The examination
consisted of a neuropsychological test battery, self-reported aspects of
psychosocial functioning, and multimodal MRI. Patients with BC reported worse
scores on several aspects of quality of life, such as higher levels of fatigue
and stress. However, cortisol levels were not elevated in the patient groups
compared to the control group. Overall cognitive performance was lower in the pre
ChT+ and the pre-ChT- groups compared to NC. Further, patients demonstrated
prefrontal hyperactivation with increasing task difficulty on a planning task
compared to NC, but not during a memory task. White matter integrity was lower in
both patient groups. No differences in regional brain volume and brain
metabolites were found. The cognitive and imaging data converged to show that
symptoms of fatigue were associated with the observed abnormalities; the observed
differences were no longer significant when fatigue was accounted for. This study
suggests that cancer-related psychological or biological processes may adversely
impact cognitive functioning and associated aspects of brain structure and
function before the start of adjuvant treatment. Our findings stress the
importance to further explore the processes underlying the expression of fatigue
and to study whether it has a contributory role in subsequent treatment-related
cognitive decline.
PMID- 25844312
TI - Multivariate pattern analysis reveals anatomical connectivity differences between
the left and right mesial temporal lobe epilepsy.
AB - Previous studies have demonstrated differences of clinical signs and functional
brain network organizations between the left and right mesial temporal lobe
epilepsy (mTLE), but the anatomical connectivity differences underlying
functional variance between the left and right mTLE remain uncharacterized. We
examined 43 (22 left, 21 right) mTLE patients with hippocampal sclerosis and 39
healthy controls using diffusion tensor imaging. After the whole-brain anatomical
networks were constructed for each subject, multivariate pattern analysis was
applied to classify the left mTLE from the right mTLE and extract the anatomical
connectivity differences between the left and right mTLE patients. The
classification results reveal 93.0% accuracy for the left mTLE versus the right
mTLE, 93.4% accuracy for the left mTLE versus controls and 90.0% accuracy for the
right mTLE versus controls. Compared with the right mTLE, the left mTLE exhibited
a different connectivity pattern in the cortical-limbic network and cerebellum.
The majority of the most discriminating anatomical connections were located
within or across the cortical-limbic network and cerebellum, thereby indicating
that these disease-related anatomical network alterations may give rise to a
portion of the complex of emotional and memory deficit between the left and right
mTLE. Moreover, the orbitofrontal gyrus, cingulate cortex, hippocampus and
parahippocampal gyrus, which exhibit high discriminative power in classification,
may play critical roles in the pathophysiology of mTLE. The current study
demonstrated that anatomical connectivity differences between the left mTLE and
the right mTLE may have the potential to serve as a neuroimaging biomarker to
guide personalized diagnosis of the left and right mTLE.
PMID- 25844313
TI - Risk, diagnostic error, and the clinical science of consciousness.
AB - In recent years, a number of new neuroimaging techniques have detected covert
awareness in some patients previously thought to be in a vegetative
state/unresponsive wakefulness syndrome. This raises worries for patients,
families, and physicians, as it indicates that the existing diagnostic error rate
in this patient group is higher than assumed. Recent research on a subset of
these techniques, called active paradigms, suggests that false positive and false
negative findings may result from applying different statistical methods to
patient data. Due to the nature of this research, these errors may be
unavoidable, and may draw into question the use of active paradigms in the
clinical setting. We argue that false positive and false negative findings carry
particular moral risks, which may bear on investigators' decisions to use certain
methods when independent means for estimating their clinical utility are absent.
We review and critically analyze this methodological problem as it relates to
both fMRI and EEG active paradigms. We conclude by drawing attention to three
common clinical scenarios where the risk of diagnostic error may be most
pronounced in this patient group.
PMID- 25844314
TI - T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease.
AB - In the current study, we have evaluated the performance of magnetic resonance
(MR) T1rho (T1rho) imaging and CSF biomarkers (T-tau, P-tau and Abeta-42) in
characterization of Alzheimer's disease (AD) patients from mild cognitive
impairment (MCI) and control subjects. With informed consent, AD (n = 27), MCI (n
= 17) and control (n = 17) subjects underwent a standardized clinical assessment
and brain MRI on a 1.5-T clinical-scanner. T1rho images were obtained at four
different spin-lock pulse duration (10, 20, 30 and 40 ms). T1rho maps were
generated by pixel-wise fitting of signal intensity as a function of the spin
lock pulse duration. T1rho values from gray matter (GM) and white matter (WM) of
medial temporal lobe were calculated. The binary logistic regression using T1rho
and CSF biomarkers as variables was performed to classify each group. T1rho was
able to predict 77.3% controls and 40.0% MCI while CSF biomarkers predicted 81.8%
controls and 46.7% MCI. T1rho and CSF biomarkers in combination predicted 86.4%
controls and 66.7% MCI. When comparing controls with AD, T1rho predicted 68.2%
controls and 73.9% AD, while CSF biomarkers predicted 77.3% controls and 78.3%
for AD. Combination of T1rho and CSF biomarkers improved the prediction rate to
81.8% for controls and 82.6% for AD. Similarly, on comparing MCI with AD, T1rho
predicted 35.3% MCI and 81.9% AD, whereas CSF biomarkers predicted 53.3% MCI and
83.0% AD. Collectively CSF biomarkers and T1rho were able to predict 59.3% MCI
and 84.6% AD. On receiver operating characteristic analysis T1rho showed higher
sensitivity while CSF biomarkers showed greater specificity in delineating MCI
and AD from controls. No significant correlation between T1rho and CSF
biomarkers, between T1rho and age, and between CSF biomarkers and age was
observed. The combined use of T1rho and CSF biomarkers have promise to improve
the early and specific diagnosis of AD. Furthermore, disease progression form MCI
to AD might be easily tracked using these two parameters in combination.
PMID- 25844315
TI - Low-frequency connectivity is associated with mild traumatic brain injury.
AB - Mild traumatic brain injury (mTBI) occurs from a closed-head impact. Often
referred to as concussion, about 20% of cases complain of secondary psychological
sequelae, such as disorders of attention and memory. Known as post-concussive
symptoms (PCS), these problems can severely disrupt the patient's quality of
life. Changes in local spectral power, particularly low-frequency amplitude
increases and/or peak alpha slowing have been reported in mTBI, but large-scale
connectivity metrics based on inter-regional amplitude correlations relevant for
integration and segregation in functional brain networks, and their association
with disorders in cognition and behaviour, remain relatively unexplored. Here, we
used non-invasive neuroimaging with magnetoencephalography to examine functional
connectivity in a resting-state protocol in a group with mTBI (n = 20), and a
control group (n = 21). We observed a trend for atypical slow-wave power changes
in subcortical, temporal and parietal regions in mTBI, as well as significant
long-range increases in amplitude envelope correlations among deep-source,
temporal, and frontal regions in the delta, theta, and alpha bands. Subsequently,
we conducted an exploratory analysis of patterns of connectivity most associated
with variability in secondary symptoms of mTBI, including inattention, anxiety,
and depression. Differential patterns of altered resting state neurophysiological
network connectivity were found across frequency bands. This indicated that
multiple network and frequency specific alterations in large scale brain
connectivity may contribute to overlapping cognitive sequelae in mTBI. In
conclusion, we show that local spectral power content can be supplemented with
measures of correlations in amplitude to define general networks that are
atypical in mTBI, and suggest that certain cognitive difficulties are mediated by
disturbances in a variety of alterations in network interactions which are
differentially expressed across canonical neurophysiological frequency ranges.
PMID- 25844316
TI - Stochastic process for white matter injury detection in preterm neonates.
AB - Preterm births are rising in Canada and worldwide. As clinicians strive to
identify preterm neonates at greatest risk of significant developmental or motor
problems, accurate predictive tools are required. Infants at highest risk will be
able to receive early developmental interventions, and will also enable
clinicians to implement and evaluate new methods to improve outcomes. While
severe white matter injury (WMI) is associated with adverse developmental
outcome, more subtle injuries are difficult to identify and the association with
later impairments remains unknown. Thus, our goal was to develop an automated
method for detection and visualization of brain abnormalities in MR images
acquired in very preterm born neonates. We have developed a technique to detect
WMI in T1-weighted images acquired in 177 very preterm born infants (24-32 weeks
gestation). Our approach uses a stochastic process that estimates the likelihood
of intensity variations in nearby pixels; with small variations being more likely
than large variations. We first detect the boundaries between normal and injured
regions of the white matter. Following this we use a measure of pixel similarity
to identify WMI regions. Our algorithm is able to detect WMI in all of the images
in the ground truth dataset with some false positives in situations where the
white matter region is not segmented accurately.
PMID- 25844317
TI - Cerebellar gray matter and lobular volumes correlate with core autism symptoms.
AB - Neuroanatomical differences in the cerebellum are among the most consistent
findings in autism spectrum disorder (ASD), but little is known about the
relationship between cerebellar dysfunction and core ASD symptoms. The newly
emerging existence of cerebellar sensorimotor and cognitive subregions provides a
new framework for interpreting the functional significance of cerebellar findings
in ASD. Here we use two complementary analyses - whole-brain voxel-based
morphometry (VBM) and the SUIT cerebellar atlas - to investigate cerebellar
regional gray matter (GM) and volumetric lobular measurements in 35 children with
ASD and 35 typically-developing (TD) children (mean age 10.4 +/- 1.6 years; range
8-13 years). To examine the relationships between cerebellar structure and core
ASD symptoms, correlations were calculated between scores on the Autism
Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and
the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM
in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and
lobular gray matter reductions in different cerebellar subregions correlated with
the severity of symptoms in social interaction, communication, and repetitive
behaviors. Structural differences and behavioral correlations converged on right
cerebellar Crus I/II, a region which shows structural and functional connectivity
with fronto-parietal and default mode networks. These results emphasize the
importance of the location within the cerebellum to the potential functional
impact of structural differences in ASD, and suggest that GM differences in
cerebellar right Crus I/II are associated with the core ASD profile.
PMID- 25844318
TI - Functional connectivity modeling of consistent cortico-striatal degeneration in
Huntington's disease.
AB - Huntington's disease (HD) is a progressive neurodegenerative disorder
characterized by a complex neuropsychiatric phenotype. In a recent meta-analysis
we identified core regions of consistent neurodegeneration in premanifest HD in
the striatum and middle occipital gyrus (MOG). For early manifest HD convergent
evidence of atrophy was most prominent in the striatum, motor cortex (M1) and
inferior frontal junction (IFJ). The aim of the present study was to functionally
characterize this topography of brain atrophy and to investigate differential
connectivity patterns formed by consistent cortico-striatal atrophy regions in
HD. Using areas of striatal and cortical atrophy at different disease stages as
seeds, we performed task-free resting-state and task-based meta-analytic
connectivity modeling (MACM). MACM utilizes the large data source of the BrainMap
database and identifies significant areas of above-chance co-activation with the
seed-region via the activation-likelihood-estimation approach. In order to
delineate functional networks formed by cortical as well as striatal atrophy
regions we computed the conjunction between the co-activation profiles of
striatal and cortical seeds in the premanifest and manifest stages of HD,
respectively. Functional characterization of the seeds was obtained using the
behavioral meta-data of BrainMap. Cortico-striatal atrophy seeds of the
premanifest stage of HD showed common co-activation with a rather cognitive
network including the striatum, anterior insula, lateral prefrontal, premotor,
supplementary motor and parietal regions. A similar but more pronounced co
activation pattern, additionally including the medial prefrontal cortex and
thalamic nuclei was found with striatal and IFJ seeds at the manifest HD stage.
The striatum and M1 were functionally connected mainly to premotor and
sensorimotor areas, posterior insula, putamen and thalamus. Behavioral
characterization of the seeds confirmed that experiments activating the MOG or
IFJ in conjunction with the striatum were associated with cognitive functions,
while the network formed by M1 and the striatum was driven by motor-related
tasks. Thus, based on morphological changes in HD, we identified functionally
distinct cortico-striatal networks resembling a cognitive and motor loop, which
may be prone to early disruptions in different stages of the disease and underlie
HD-related cognitive and motor symptom profiles. Our findings provide an
important link between morphometrically defined seed-regions and corresponding
functional circuits highlighting the functional and ensuing clinical relevance of
structural damage in HD.
PMID- 25844319
TI - ADHD severity is associated with white matter microstructure in the subgenual
cingulum.
AB - AIMS: This analysis examined hypothesised associations between microstructural
attributes in specific white matter (WM) tracts selected a priori and measures of
clinical variability in adolescents with a diagnosis of attention deficit
hyperactivity disorder (ADHD). Firstly, associations were explored between WM
microstructure and ADHD severity in the subgenual cingulum. Secondly, to ensure
that tract-specific approaches afforded enhanced rather than differential
sensitivity, associations were measured between WM microstructure and autistic
traits in the right corticospinal tract based on results of a previously
published voxelwise analysis. METHODS: 40 right-handed males aged 14-18 years (19
with DSM-IV combined type ADHD and 21 healthy controls) underwent a 60 direction
diffusion MRI scan. Clinical ADHD and autism variation were assessed by validated
questionnaires. Deterministic tractography based on spherical deconvolution
methods was used to map the subgenual cingulum and corticospinal tract. RESULTS:
Fractional anisotropy was positively correlated and radial diffusivity was
negatively correlated with a) ADHD severity in the left subgenual cingulum and b)
autistic traits in the inferior segment of the right corticospinal tract. No case
control differences were found. CONCLUSIONS: Results shed light on possible
anatomical correlates of ADHD severity and autistic symptoms in pathways which
may be involved in the ADHD phenotype. They provide further evidence that tract
specific approaches may a) reveal associations between microstructural metrics
and indices of phenotypic variability which would not be detected using voxelwise
approaches, and b) provide improved rather than differential sensitivity compared
to voxelwise approaches.
PMID- 25844320
TI - Cardiorespiratory fitness and its association with thalamic, hippocampal, and
basal ganglia volumes in multiple sclerosis.
AB - BACKGROUND: There is little known about cardiorespiratory fitness and its
association with volumes of the thalamus, hippocampus, and basal ganglia in
multiple sclerosis (MS). Such inquiry is important for identifying a possible
behavioral approach (e.g., aerobic exercise training) that might change volumes
of deep gray matter (DGM) structures associated with cognitive and motor
functions in MS. PURPOSE: This study examined the association between
cardiorespiratory fitness and volumes of the thalamus, hippocampus, and basal
ganglia in MS. METHOD: We enrolled 35 persons with MS who underwent a maximal
exercise test for measuring cardiorespiratory fitness as peak oxygen consumption
(VO2peak) and brain MRI. Volumes of the thalamus, hippocampus, caudate, putamen,
and pallidum were calculated from 3D T1-weighted structural brain images. We
examined associations using partial (pr) correlations controlling for demographic
and clinical variables. RESULTS: VO2peak was significantly associated with
composite scaled volumes of the caudate(pr = .47, p < .01), putamen (pr = .44, p
< .05), pallidum (pr = .40, p < .05), and hippocampus (pr = .42, p < .05), but
not thalamus (pr = .31, p = .09), when controlling for sex, age, disability, and
duration of MS. CONCLUSION: Our results provide novel evidence that
cardiorespiratory fitness is associated with volumes of DGM structures that are
involved in motor and cognitive functions in MS.
PMID- 25844321
TI - Fibromyalgia is characterized by altered frontal and cerebellar structural
covariance brain networks.
AB - Altered brain morphometry has been widely acknowledged in chronic pain, and
recent studies have implicated altered network dynamics, as opposed to properties
of individual brain regions, in supporting persistent pain. Structural covariance
analysis determines the inter-regional association in morphological metrics, such
as gray matter volume, and such structural associations may be altered in chronic
pain. In this study, voxel-based morphometry structural covariance networks were
compared between fibromyalgia patients (N = 42) and age- and sex-matched pain
free adults (N = 63). We investigated network topology using spectral
partitioning, which can delineate local network submodules with consistent
structural covariance. We also explored white matter connectivity between regions
comprising these submodules and evaluated the association between probabilistic
white matter tractography and pain-relevant clinical metrics. Our structural
covariance network analysis noted more connections within the cerebellum for
fibromyalgia patients, and more connections in the frontal lobe for healthy
controls. For fibromyalgia patients, spectral partitioning identified a distinct
submodule with cerebellar connections to medial prefrontal and temporal and right
inferior parietal lobes, whose gray matter volume was associated with the
severity of depression in these patients. Volume for a submodule encompassing
lateral orbitofrontal, inferior frontal, postcentral, lateral temporal, and
insular cortices was correlated with evoked pain sensitivity. Additionally, the
number of white matter fibers between specific submodule regions was also
associated with measures of evoked pain sensitivity and clinical pain
interference. Hence, altered gray and white matter morphometry in cerebellar and
frontal cortical regions may contribute to, or result from, pain-relevant
dysfunction in chronic pain patients.
PMID- 25844323
TI - Predictive value of different conventional and non-conventional MRI-parameters
for specific domains of cognitive function in multiple sclerosis.
AB - OBJECTIVE: While many studies correlated cognitive function with changes in brain
morphology in multiple sclerosis (MS), few of them used a multi-parametric
approach in a single dataset so far. We thus here assessed the predictive value
of different conventional and quantitative MRI-parameters both for overall and
domain-specific cognitive performance in MS patients from a single center.
METHODS: 69 patients (17 clinically isolated syndrome, 47 relapsing-remitting MS,
5 secondary-progressive MS) underwent the "Brief Repeatable Battery of
Neuropsychological Tests" assessing overall cognition, cognitive efficiency and
memory function as well as MRI at 3 Tesla to obtain T2-lesion load (T2-LL),
normalized brain volume (global brain volume loss), normalized cortical volume
(NCV), normalized thalamic volume (NTV), normalized hippocampal volume (NHV),
normalized caudate nuclei volume (NCNV), basal ganglia R2* values (iron
deposition) and magnetization transfer ratios (MTRs) for cortex and normal
appearing brain tissue (NABT). RESULTS: Regression models including clinical,
demographic variables and MRI-parameters explained 22-27% of variance of overall
cognition, 17-26% of cognitive efficiency and 22-23% of memory. NCV, T2-LL and
MTR of NABT were the strongest predictors of overall cognitive function.
Cognitive efficiency was best predicted by NCV, T2-LL and iron deposition in the
basal ganglia. NTV was the strongest predictor for memory function and NHV was
particularly related to memory function. CONCLUSIONS: The predictive value of
distinct MRI-parameters differs for specific domains of cognitive function, with
a greater impact of cortical volume, focal and diffuse white matter abnormalities
on overall cognitive function, an additional role of basal ganglia iron
deposition on cognitive efficiency, and thalamic and hippocampal volume on memory
function. This suggests the usefulness of using multiparametric MRI to assess
(micro)structural correlates of different cognitive constructs.
PMID- 25844322
TI - Response of the medial temporal lobe network in amnestic mild cognitive
impairment to therapeutic intervention assessed by fMRI and memory task
performance.
AB - Studies of individuals with amnestic mild cognitive impairment (aMCI) have
detected hyperactivity in the hippocampus during task-related functional magnetic
resonance imaging (fMRI). Such elevated activation has been localized to the
hippocampal dentate gyrus/CA3 (DG/CA3) during performance of a task designed to
detect the computational contributions of those hippocampal circuits to episodic
memory. The current investigation was conducted to test the hypothesis that
greater hippocampal activation in aMCI represents a dysfunctional shift in the
normal computational balance of the DG/CA3 regions, augmenting CA3-driven pattern
completion at the expense of pattern separation mediated by the dentate gyrus. We
tested this hypothesis using an intervention based on animal research
demonstrating a beneficial effect on cognition by reducing excess hippocampal
neural activity with low doses of the atypical anti-epileptic levetiracetam. In a
within-subject design we assessed the effects of levetiracetam in three cohorts
of aMCI participants, each receiving a different dose of levetiracetam. Elevated
activation in the DG/CA3 region, together with impaired task performance, was
detected in each aMCI cohort relative to an aged control group. We observed
significant improvement in memory task performance under drug treatment relative
to placebo in the aMCI cohorts at the 62.5 and 125 mg BID doses of levetiracetam.
Drug treatment in those cohorts increased accuracy dependent on pattern
separation processes and reduced errors attributable to an over-riding effect of
pattern completion while normalizing fMRI activation in the DG/CA3 and entorhinal
cortex. Similar to findings in animal studies, higher dosing at 250 mg BID had no
significant benefit on either task performance or fMRI activation. Consistent
with predictions based on the computational functions of the DG/CA3 elucidated in
basic animal research, these data support a dysfunctional encoding mechanism
detected by fMRI in individuals with aMCI and therapeutic intervention using fMRI
to detect target engagement in response to treatment.
PMID- 25844324
TI - Diffuse alterations in grey and white matter associated with cognitive impairment
in Shwachman-Diamond syndrome: evidence from a multimodal approach.
AB - Shwachman-Diamond syndrome is a rare recessive genetic disease caused by
mutations in SBDS gene, at chromosome 7q11. Phenotypically, the syndrome is
characterized by exocrine pancreatic insufficiency, bone marrow dysfunction,
skeletal dysplasia and variable cognitive impairments. Structural brain
abnormalities (smaller head circumference and decreased brain volume) have also
been reported. No correlation studies between brain abnormalities and
neuropsychological features have yet been performed. In this study we investigate
neuroanatomical findings, neurofunctional pathways and cognitive functioning of
Shwachman-Diamond syndrome subjects compared with healthy controls. To be
eligible for inclusion, participants were required to have known SBDS mutations
on both alleles, no history of cranial trauma or any standard contraindication to
magnetic resonance imaging. Appropriate tests were used to assess cognitive
functions. The static images were acquired on a 3 * 0 T magnetic resonance
scanner and blood oxygen level-dependent functional magnetic resonance imaging
data were collected both during the execution of the Stroop task and at rest.
Diffusion tensor imaging was used to assess brain white matter. The Tract-based
Spatial Statistics package and probabilistic tractography were used to
characterize white matter pathways. Nine participants (5 males), half of all the
subjects aged 9-19 years included in the Italian Shwachman-Diamond Syndrome
Registry, were evaluated and compared with nine healthy subjects, matched for sex
and age. The patients performed less well than norms and controls on cognitive
tasks (p = 0.0002). Overall, cortical thickness was greater in the patients, both
in the left (+10%) and in the right (+15%) hemisphere, significantly differently
increased in the temporal (left and right, p = 0.04), and right parietal (p =
0.03) lobes and in Brodmann area 44 (p = 0.04) of the right frontal lobe. The
greatest increases were observed in the left limbic-anterior cingulate cortex
(>=43%, p < 0.0004). Only in Broca's area in the left hemisphere did the patients
show a thinner cortical thickness than that of controls (p = 0.01). Diffusion
tensor imaging showed large, significant difference increases in both fractional
anisotropy (+37%, p < 0.0001) and mean diffusivity (+35%, p < 0.005); the Tract
based Spatial Statistics analysis identified six abnormal clusters of white
matter fibres in the fronto-callosal, right fronto-external capsulae, left fronto
parietal, right pontine, temporo-mesial and left anterior-medial-temporal
regions. Brain areas activated during the Stroop task and those active during the
resting state, are different, fewer and smaller in patients and correlate with
worse performance (p = 0.002). Cognitive impairment in Shwachman-Diamond syndrome
subjects is associated with diffuse brain anomalies in the grey matter (verbal
skills with BA44 and BA20 in the right hemisphere; perceptual skills with BA5,
37, 20, 21, 42 in the left hemisphere) and white matter connectivity (verbal
skills with alterations in the fronto-occipital fasciculus and with the inferior
longitudinal fasciculus; perceptual skills with the arcuate fasciculus, limbic
and ponto-cerebellar fasciculus; memory skills with the arcuate fasciculus;
executive functions with the anterior cingulated and arcuate fasciculus).
PMID- 25844325
TI - Developmental changes in large-scale network connectivity in autism.
AB - BACKGROUND: Disrupted cortical connectivity is thought to underlie the complex
cognitive and behavior profile observed in individuals with autism spectrum
disorder (ASD). Previous neuroimaging research has identified patterns of both
functional hypo- and hyper-connectivity in individuals with ASD. A recent theory
attempting to reconcile conflicting results in the literature proposes that hyper
connectivity of brain networks may be more characteristic of young children with
ASD, while hypo-connectivity may be more prevalent in adolescents and adults with
the disorder when compared to typical development (TD) (Uddin etal., 2013).
Previous work has examined only young children, mixed groups of children and
adolescents, or adult cohorts in separate studies, leaving open the question of
developmental influences on functional brain connectivity in ASD. METHODS: The
current study tests this developmental hypothesis by examining within- and
between-network resting state functional connectivity in a large sample of 26
children, 28 adolescents, and 18 adults with ASD and age- and IQ-matchedTD
individuals for the first time using an entirely data-driven approach.
Independent component analyses (ICA) and dual regression was applied to data from
three age cohorts to examine the effects of participant age on patterns of within
networkwhole-brain functional connectivity in individuals with ASD compared with
TD individuals. Between-network connectivity differences were examined for each
age cohort by comparing correlations between ICA components across groups.
RESULTS: We find that in the youngest cohort (age 11 and under), children with
ASD exhibit hyper-connectivity within large-scale brain networks as well as
decreased between-network connectivity compared with age-matchedTD children. In
contrast, adolescents with ASD (age 11-18) do not differ from TD adolescents in
within-network connectivity, yet show decreased between-network connectivity
compared with TD adolescents. Adults with ASD show no within- or between-network
differences in functional network connectivity compared with neurotypical age
matched individuals. CONCLUSIONS: Characterizing within- and between-network
functional connectivity in age-stratified cohorts of individuals with ASD and TD
individuals demonstrates that functional connectivity atypicalities in the
disorder are not uniform across the lifespan. These results demonstrate how
explicitly characterizing participant age and adopting a developmental
perspective can lead to a more nuanced understanding of atypicalities of
functional brain connectivity in autism.
PMID- 25844327
TI - Co-localization between the BOLD response and epileptiform discharges recorded by
simultaneous intracranial EEG-fMRI at 3 T.
AB - OBJECTIVES: Simultaneous scalp EEG-fMRI can identify hemodynamic changes
associated with the generation of interictal epileptiform discharges (IEDs), and
it has the potential of becoming a standard, non-invasive technique for pre
surgical assessment of patients with medically intractable epilepsy. This study
was designed to assess the BOLD response to focal IEDs recorded via simultaneous
intracranial EEG-functional MRI (iEEG-fMRI). METHODS: Twelve consecutive patients
undergoing intracranial video EEG monitoring were recruited for iEEG-fMRI studies
at 3 T. Depth, subdural strip, or grid electrodes were implanted according to our
standard clinical protocol. Subjects underwent 10-60 min of continuous iEEG-fMRI
scanning. IEDs were marked, and the most statistically significant clusters of
BOLD signal were identified (Z-score 2.3, p value < 0.05). We assessed the
concordance between the locations of the BOLD response and the IED. Concordance
was defined as a distance <1.0 cm between the IED and BOLD response location.
Negative BOLD responses were not studied in this project. RESULTS: Nine patients
(7 females) with a mean age of 31 years (range 22-56) had 11 different types of
IEDs during fMR scanning. The IEDs were divided based on the location of the
active electrode contact into mesial temporal, lateral temporal, and extra
temporal. Seven (5 left) mesial temporal IED types were recorded in 5 patients
(110-2092 IEDs per spike location). Six of these IEDs had concordant BOLD
response in the ipsilateral mesial temporal structures, <1 cm from the most
active contact. One of the two subjects with left lateral temporal IEDs had BOLD
responses concordant with the location of the most active contact, as well other
ipsilateral and contralateral sites. Notably, the remaining two subjects with
extratemporal discharges showed no BOLD signal near the active electrode contact.
CONCLUSIONS: iEEG-fMRI is a feasible and low-risk method for assessment of
hemodynamic changes of very focal IEDs that may not be recorded by scalp EEG. A
high concordance rate between the location of the BOLD response and IEDs was seen
for mesial temporal (6/7) IEDs. Significant BOLD activation was also seen in
areas distant from the active electrode and these sites exhibited maximal BOLD
activation in the majority of cases. This implies that iEEG-fMRI may further
describe the areas involved in the generation of IEDs beyond the vicinity of the
electrode(s).
PMID- 25844326
TI - Dyslexic children lack word selectivity gradients in occipito-temporal and
inferior frontal cortex.
AB - fMRI studies using a region-of-interest approach have revealed that the ventral
portion of the left occipito-temporal cortex, which is specialized for
orthographic processing of visually presented words (and includes the so-called
"visual word form area", VWFA), is characterized by a posterior-to-anterior
gradient of increasing selectivity for words in typically reading adults,
adolescents, and children (e.g. Brem et al., 2006, 2009). Similarly, the left
inferior frontal cortex (IFC) has been shown to exhibit a medial-to-lateral
gradient of print selectivity in typically reading adults (Vinckier et al.,
2007). Functional brain imaging studies of dyslexia have reported relative
underactivity in left hemisphere occipito-temporal and inferior frontal regions
using whole-brain analyses during word processing tasks. Hence, the question
arises whether gradient sensitivities in these regions are altered in dyslexia.
Indeed, a region-of-interest analysis revealed the gradient-specific functional
specialization in the occipito-temporal cortex to be disrupted in dyslexic
children (van der Mark et al., 2009). Building on these studies, we here (1)
investigate if a word-selective gradient exists in the inferior frontal cortex in
addition to the occipito-temporal cortex in normally reading children, (2)
compare typically reading with dyslexic children, and (3) examine functional
connections between these regions in both groups. We replicated the previously
reported anterior-to-posterior gradient of increasing selectivity for words in
the left occipito-temporal cortex in typically reading children, and its absence
in the dyslexic children. Our novel finding is the detection of a pattern of
increasing selectivity for words along the medial-to-lateral axis of the left
inferior frontal cortex in typically reading children and evidence of functional
connectivity between the most lateral aspect of this area and the anterior
aspects of the occipito-temporal cortex. We report absence of an IFC gradient and
connectivity between the lateral aspect of the IFC and the anterior occipito
temporal cortex in the dyslexic children. Together, our results provide insights
into the source of the anomalies reported in previous studies of dyslexia and add
to the growing evidence of an orthographic role of IFC in reading.
PMID- 25844328
TI - Schizophrenia risk variants modulate white matter volume across the psychosis
spectrum: evidence from two independent cohorts.
AB - Polygenic risk scores, based on risk variants identified in genome-wide
association-studies (GWAS), explain a considerable portion of the heritability
for schizophrenia (SZ) and bipolar disorder (BD). However, little is known about
the combined effects of these variants, although polygenic neuroimaging has
developed into a powerful tool of translational neuroscience. In this study, we
used genome wide significant SZ risk variants to test the predictive capacity of
the polygenic model and explored potential associations with white matter volume,
a key candidate in imaging phenotype for psychotic disorders. By calculating the
combined additive schizophrenia risk of seven SNPs (significant hits from a
recent schizophrenia GWAS study), we show that increased additive genetic risk
for SZ was associated with reduced white matter volume in a group of participants
(n = 94) consisting of healthy individuals, SZ first-degree relatives, SZ
patients and BD patients. This effect was also seen in a second independent
sample of healthy individuals (n = 89). We suggest that a moderate portion of
variance (~4%) of white matter volume can be explained by the seven hits from the
recent schizophrenia GWAS. These results provide evidence for associations
between cumulative genetic risk for schizophrenia and intermediate neuroimaging
phenotypes in models of psychosis. Our work contributes to a growing body of
literature suggesting that polygenic risk may help to explain white matter
alterations associated with familial risk for psychosis.
PMID- 25844329
TI - Comparing a diffusion tensor and non-tensor approach to white matter fiber
tractography in chronic stroke.
AB - Diffusion tensor imaging (DTI)-based tractography has been used to demonstrate
functionally relevant differences in white matter pathway status after stroke.
However, it is now known that the tensor model is insensitive to the complex
fiber architectures found in the vast majority of voxels in the human brain. The
inability to resolve intra-voxel fiber orientations may have important
implications for the utility of standard DTI-based tract reconstruction methods.
Intra-voxel fiber orientations can now be identified using novel, tensor-free
approaches. Constrained spherical deconvolution (CSD) is one approach to
characterize intra-voxel diffusion behavior. In the current study, we performed
DTI- and CSD-based tract reconstruction of the corticospinal tract (CST) and
corpus callosum (CC) to test the hypothesis that characterization of complex
fiber orientations may improve the robustness of fiber tract reconstruction and
increase the sensitivity to identify functionally relevant white matter
abnormalities in individuals with chronic stroke. Diffusion weighted magnetic
resonance imaging was performed in 27 chronic post-stroke participants and 12
healthy controls. Transcallosal pathways and the CST bilaterally were
reconstructed using DTI- and CSD-based tractography. Mean fractional anisotropy
(FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial
diffusivity (RD) were calculated across the tracts of interest. The total number
and volume of reconstructed tracts was also determined. Diffusion measures were
compared between groups (Stroke, Control) and methods (CSD, DTI). The
relationship between post-stroke motor behavior and diffusion measures was
evaluated. Overall, CSD methods identified more tracts than the DTI-based
approach for both CC and CST pathways. Mean FA, ADC, and RD differed between DTI
and CSD for CC-mediated tracts. In these tracts, we discovered a difference in FA
for the CC between stroke and healthy control groups using CSD but not DTI. CSD
identified ipsilesional CST pathways in 9 stroke participants who did not have
tracts identified with DTI. Additionally, CSD differentiated between stroke
ipsilesional and healthy control non-dominant CST for several measures (number of
tracts, tract volume, FA, ADC, and RD) whereas DTI only detected group
differences for number of tracts. In the stroke group, motor behavior correlated
with fewer diffusion metrics derived from the DTI as compared to CSD
reconstructed ipsilesional CST and CC. CSD is superior to DTI-based tractography
in detecting differences in diffusion characteristics between the nondominant
healthy control and ipsilesional CST. CSD measures of microstructure tissue
properties related to more motor outcomes than DTI measures did. Our results
suggest the potential utility and functional relevance of characterizing complex
fiber organization using tensor-free diffusion modeling approaches to investigate
white matter pathways in the brain after stroke.
PMID- 25844330
TI - Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis.
AB - Limb weakness in amyotrophic lateral sclerosis (ALS) is typically asymmetric.
Previous studies have identified an effect of limb dominance on onset and spread
of weakness, however relative atrophy of dominant and non-dominant brain regions
has not been investigated. Our objective was to use voxel-based morphometry (VBM)
to explore gray matter (GM) asymmetry in ALS, in the context of limb dominance.
30 ALS subjects were matched with 17 healthy controls. All subjects were right
handed. Each underwent a structural MRI sequence, from which GM segmentations
were generated. Patterns of GM atrophy were assessed in ALS subjects with first
weakness in a right-sided limb (n = 15) or left-sided limb (n = 15). Within each
group, a voxelwise comparison was also performed between native and mirror GM
images, to identify regions of hemispheric GM asymmetry. Subjects with ALS showed
disproportionate atrophy of the dominant (left) motor cortex hand area,
irrespective of the side of first limb weakness (p < 0.01). Asymmetric atrophy of
the left somatosensory cortex and temporal gyri was only observed in ALS subjects
with right-sided onset of limb weakness. Our VBM protocol, contrasting native and
mirror images, was able to more sensitively detect asymmetric GM pathology in a
small cohort, compared with standard methods. These findings indicate particular
vulnerability of dominant upper limb representation in ALS, supporting previous
clinical studies, and with implications for cortical organisation and selective
vulnerability.
PMID- 25844331
TI - T2 mapping outperforms normalised FLAIR in identifying hippocampal sclerosis.
AB - RATIONALE: Qualitatively, FLAIR MR imaging is sensitive to the detection of
hippocampal sclerosis (HS). Quantitative analysis of T2 maps provides a useful
objective measure and increased sensitivity over visual inspection of T2-weighted
scans. We aimed to determine whether quantification of normalised FLAIR is as
sensitive as T2 mapping in detection of HS. METHOD: Dual echo T2 and FLAIR MR
images were retrospectively analysed in 27 patients with histologically confirmed
HS and increased T2 signal in ipsilateral hippocampus and 14 healthy controls.
Regions of interest were manually segmented in all hippocampi aiming to avoid
inclusion of CSF. Hippocampal T2 values and measures of normalised FLAIR Signal
Intensity (nFSI) were compared in healthy and sclerotic hippocampi. RESULTS: HS
was identified on T2 values with 100% sensitivity and 100% specificity. HS was
identified on nFSI measures with 60% sensitivity and 93% specificity. CONCLUSION:
T2 mapping is superior to nFSI for identification of HS.
PMID- 25844332
TI - Is the double channel gastroscope useful in endoscopic mucosal resection for
large sessile colon polyps?
PMID- 25844333
TI - Which needle is better for diagnosing subepithelial lesions?
PMID- 25844334
TI - Is endoscopic ultrasonography-guided fine needle aspiration trailblazing in
tissue sampling of adrenal masses?
PMID- 25844335
TI - Endoscopic management of nonvariceal upper gastrointestinal bleeding: state of
the art.
AB - Nonvariceal upper gastrointestinal (GI) bleeding is one of the most common
reasons for hospitalization and a major cause of morbidity and mortality
worldwide. Recently developed endoscopic devices and supporting apparatuses can
achieve endoscopic hemostasis with greater safety and efficiency. With these
advancements in technology and technique, gastroenterologists should have no
concerns regarding the management of acute upper GI bleeding, provided that they
are well prepared and trained. However, when endoscopic hemostasis fails,
endoscopy should not be continued. Rather, endoscopists should refer patients to
radiologists and surgeons without any delay for evaluation regarding the
appropriateness of emergency interventional radiology or surgery.
PMID- 25844336
TI - Endoscopic management of mallory-weiss tearing.
AB - Mallory-Weiss tearing (MWT) is a common cause of non-variceal upper
gastrointestinal bleeding. Although the majority of patients with bleeding MWT
require no intervention other than hemodynamic supports, spectrum of MWT is wide,
and the condition sometimes results in a fatal outcome. Endoscopic management to
stop the bleeding may be required during the index endoscopy, especially in those
with active bleeding or stigmata of recurrent bleeding. Most commonly used
endoscopic treatment for actively bleeding MWT is injection therapy, argon plasma
coagulation, hemoclip placement, and band ligation. Selection of the optimal
endoscopic hemostasis depends on the physician's ability and patient's clinical
status.
PMID- 25844337
TI - Endoscopic management of peptic ulcer bleeding.
AB - Acute upper gastrointestinal bleeding is a common medical emergency around the
world and the major cause is peptic ulcer bleeding. Endoscopic treatment is
fundamental for the management of peptic ulcer bleeding. Despite recent advances
in endoscopic treatment, mortality from peptic ulcer bleeding has still remained
high. This is because the disease often occurs in elderly patients with frequent
comorbidities and are taking ulcerogenic medications. Therefore, the management
of peptic ulcer bleeding is still a challenge for clinicians. This article
reviews the various endoscopic methods available for management of peptic ulcer
bleeding and the techniques in using these methods.
PMID- 25844338
TI - Endoscopic Management of Dieulafoy's Lesion.
AB - A Dieulafoy's lesion is a vascular abnormality consisting of a large caliber
persistent tortuous submucosal artery. A small mucosal defect with the eruption
of this protruding vessel can cause bleeding. In fact, a Dieulafoy's lesion is a
relatively rare but potentially life-threatening condition. It accounts for 1% to
2% of cases of acute gastrointestinal bleeding. Although there is no consensus on
the treatment of Dieulafoy's lesions; treatment options depend on the mode of
presentation, site of the lesion, and available expertise. Endoscopic therapy is
usually successful in achieving primary hemostasis, with hemostasis success rates
reaching 75% to 100%. Although various therapeutic endoscopic methods are used to
control bleeding in Dieulafoy's lesions, the best method for endoscopic
intervention is not clear. Combination endoscopic therapy is known to be superior
to monotherapy because of a lower rate of recurrent bleeding. In addition,
mechanical therapies including hemostatic clipping and endoscopic band ligation
are more effective and successful in controlling bleeding than other endoscopic
methods. Advances in endoscopic techniques have reduced mortality in patients
with Dieulafoy's lesion-from 80% to 8%-and consequently, the need for surgical
intervention has been reduced. Currently, surgical intervention is used for cases
that fail therapeutic endoscopic or angiographic interventions.
PMID- 25844339
TI - Endoscopic management of tumor bleeding from inoperable gastric cancer.
AB - Tumor bleeding is not a rare complication in patients with inoperable gastric
cancer. Endoscopy has important roles in the diagnosis and primary treatment of
tumor bleeding, similar to its roles in other non-variceal upper gastrointestinal
bleeding cases. Although limited studies have been performed, endoscopic therapy
has been highly successful in achieving initial hemostasis. One or a combination
of endoscopic therapy modalities, such as injection therapy, mechanical therapy,
or ablative therapy, can be used for hemostasis in patients with endoscopic
stigmata of recent hemorrhage. However, rebleeding after successful hemostasis
with endoscopic therapy frequently occurs. Endoscopic therapy may be a treatment
option for successfully controlling this rebleeding. Transarterial embolization
or palliative surgery should be considered when endoscopic therapy fails. For
primary and secondary prevention of tumor bleeding, proton pump inhibitors can be
prescribed, although their effectiveness to prevent bleeding remains to be
investigated.
PMID- 25844340
TI - Guidelines for video capsule endoscopy: emphasis on Crohn's disease.
AB - Video capsule endoscopy (VCE) is an ingestible video camera that transmits high
quality images of the small intestinal mucosa. This makes the small intestine
more readily accessible to physicians investigating the presence of small bowel
disorders, such as Crohn's disease (CD). Although VCE is frequently performed in
Korea, there are no evidence-based guidelines on the appropriate use of VCE in
the diagnosis of CD. To provide accurate information and suggest correct testing
approaches for small bowel diseases, the Korean Gut Image Study Group, part of
the Korean Society of Gastrointestinal Endoscopy, developed guidelines on VCE.
Teams were set up to develop guidelines on VCE. Four areas were selected:
diagnosis of obscure gastrointestinal bleeding, small bowel preparation for VCE,
diagnosis of CD, and diagnosis of small bowel tumors. Three key questions were
selected regarding the role of VCE in CD. In preparing these guidelines, a
systematic literature search, evaluation, selection, and meta-analysis were
performed. After writing a draft of the guidelines, the opinions of various
experts were solicited before producing the final document. These guidelines are
expected to play a role in the diagnosis of CD. They will need to be updated as
new data and evidence become available.
PMID- 25844341
TI - Use of a double-channel gastroscope reduces procedural time in large left-sided
colonic endoscopic mucosal resections.
AB - BACKGROUND/AIMS: Endoscopic mucosal resection (EMR) of large colorectal lesions
is associated with increased procedural time. The objective of this study was to
evaluate the effect of double-channel gastroscope (DCG) use on the procedural
time of EMRs in the rectosigmoid area. METHODS: All EMRs for sessile or flat
rectosigmoid lesions >=2 cm performed between July 2011 and September 2012 were
retrospectively analyzed. RESULTS: There were 55 lesions >=2 cm in the
rectosigmoid area in 55 patients, of which 26 were removed by EMR using a DCG (DC
group) and 29 by using an ordinary colonoscope or gastroscope (OS group). The
mean size of the removed polyps, morphology, adverse effects, and other
parameters were similar between the two groups. The mean procedural time was
significantly lower in the DC group than in the OS group (24.4+/-18.3 minutes vs.
36.3+/-24.4 minutes, p=0.015). Moreover, in a subgroup of patients with polyps
>40 mm, the statistical difference in the mean procedural time between the DC and
OS groups was even more pronounced (33+/-21 minutes vs. 58.7+/-20.6 minutes,
p=0.004). CONCLUSIONS: Our data suggest that the use of a DCG in the resection of
large nonpedunculated rectosigmoid lesions significantly reduces the procedural
time.
PMID- 25844342
TI - Light-emitting diode-assisted narrow band imaging video endoscopy system in head
and neck cancer.
AB - BACKGROUND/AIMS: To validate the effectiveness of a newly developed light
emitting diode (LED)-narrow band imaging (NBI) system for detecting early
malignant tumors in the oral cavity. METHODS: Six men (mean age, 51.5 years) with
early oral mucosa lesions were screened using both the conventional white light
and LED-NBI systems. RESULTS: Small elevated or ulcerative lesions were found
under the white light view, and typical scattered brown spots were identified
after shifting to the LED-NBI view for all six patients. Histopathological
examination confirmed squamous cell carcinoma. The clinical stage was early
malignant lesions (T1), and the patients underwent wide excision for primary
cancer. This is the pilot study documenting the utility of a new LED-NBI system
as an adjunctive technique to detect early oral cancer using the diagnostic
criterion of the presence of typical scattered brown spots in six high-risk
patients. CONCLUSIONS: Although large-scale screening programs should be
established to further verify the accuracy of this technology, its lower power
consumption, lower heat emission, and higher luminous efficiency appear promising
for future clinical applications.
PMID- 25844343
TI - Clinical outcomes of argon plasma coagulation therapy for early gastric
neoplasms.
AB - BACKGROUND/AIMS: Argon plasma coagulation (APC) has some merits in the treatment
of gastric neoplasms including a shorter operative time and fewer complications
compared with endoscopic mucosal resection or endoscopic submucosal dissection.
However, there are few reports on the outcomes of gastric neoplasms treated using
APC. The aim of this study was to evaluate APC in the treatment of early gastric
neoplasms in terms of clinical efficacy, safety, and local recurrence. METHODS:
We enrolled 28 patients who received APC therapy at the Kyungpook National
University Hospital between May 2007 and April 2013. Clinical outcomes were
analyzed. RESULTS: The median follow-up period was 24.8 months (range, 2 to 78).
Among the 28 lesions treated using the APC procedure, tumor recurrence was
encountered in seven lesions (25.0%). Recurrence was found in 50% (5/10) of
single APC cases and 11% (2/18) of rescue APC cases. The mean time to recurrence
was 16.1 months (range, 2 to 78). There were no serious APC-related complications
such as perforation, bleeding, or infection. CONCLUSIONS: APC therapy can be a
useful treatment with a favorable safety profile for patients with early gastric
neoplasms. However, further studies are necessary to determine the long-term
prognosis of patients undergoing this treatment.
PMID- 25844344
TI - Yields and Utility of Endoscopic Ultrasonography-Guided 19-Gauge Trucut Biopsy
versus 22-Gauge Fine Needle Aspiration for Diagnosing Gastric Subepithelial
Tumors.
AB - BACKGROUND/AIMS: To evaluate the yields and utility of 19-gauge (G) Trucut biopsy
(TCB) versus 22 G fine needle aspiration (FNA) for diagnosing gastric
subepithelial tumors (SETs). METHODS: We retrieved data for 152 patients with a
gastric SET larger than 2 cm who had undergone endoscopic ultrasonography (EUS)
guided 19 G TCB (n=90) or 22 G FNA (n=62). Relevant clinical, tumor-specific, and
EUS procedural information was reviewed retrospectively. RESULTS: A specific
diagnosis was made for 76 gastrointestinal stromal tumors (GISTs) and 51 non-GIST
SETs. The diagnostic yield of TCB was greater than that of FNA (77.8% vs. 38.7%,
p<0.001). The percentage of non-diagnostic specimens (suspicious and
insufficient) was significantly lower in the TCB group (6.7% and 15.5%,
respectively) than in the FNA group (22.6% and 38.7%, respectively; both
p<0.001). TCB accurately diagnosed 90.9% of GISTs and 81.1% of non-GIST SETs,
whereas FNA accurately diagnosed 68.8% of GISTs and 14.3% of non-GIST SETs. There
were nine technical failures with TCB, and the rate of adverse events did not
differ between the groups (TCB vs. FNA, 3.3% vs. 8.1%; p=0.27). CONCLUSIONS:
Nineteen-gauge TCB is safe and highly valuable for diagnosing gastric SETs larger
than 2 cm if technical failure can be avoided.
PMID- 25844345
TI - Endoscopic ultrasonography-guided ethanol ablation for small pancreatic
neuroendocrine tumors: results of a pilot study.
AB - BACKGROUND/AIMS: Endoscopic ultrasonography (EUS)-guided ethanol ablation is
gaining popularity for the treatment of focal pancreatic lesions. The aim of this
study was to evaluate the safety, feasibility, and treatment response after EUS
guided ethanol injection for small pancreatic neuroendocrine tumors (p-NETs).
METHODS: This was a retrospective analysis of a prospectively collected database
including 11 consecutive patients with p-NETs who underwent EUS-guided ethanol
injection. RESULTS: EUS-guided ethanol injection was successfully performed in 11
patients with 14 tumors. The final diagnosis was based on histology and clinical
signs as follows: 10 non-functioning neuroendocrine tumors and four insulinomas.
During follow-up (median, 370 days; range, 152 to 730 days), 10 patients
underwent clinical follow-up after treatment, and one patient was excluded
because of loss to follow-up. A single treatment session with an injection of 0.5
to 3.8 mL of ethanol resulted in complete responses (CRs) at the 3-month
radiologic imaging for seven of 13 tumors (response rate, 53.8%). Multiple
treatment sessions performed in three tumors with residual viable enhancing
tissue increased the number of tumors with CRs to eight of 13 (response rate,
61.5%). Mild pancreatitis occurred in three of 11 patients. CONCLUSIONS: EUS
guided ethanol injection appears to be a safe, feasible, and potentially
effective method for treating small p-NETs in patients who are poor surgical
candidates.
PMID- 25844346
TI - Endoscopic ultrasound-guided fine-needle aspiration of the adrenal glands:
analysis of 21 patients.
AB - BACKGROUND/AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)
cytology of adrenal masses helps in etiological diagnosis. The aim of this study
was to evaluate the diagnostic yield of EUS-FNA of adrenal masses in cases where
other imaging methods failed and/or were not feasible. METHODS: Twenty-one
consecutive patients with adrenal masses, in whom adrenal FNA was performed
because conventional imaging modalities failed and/or were not feasible, were
prospectively evaluated over a period of 3 years. RESULTS: Of the 21 patients
(mean age, 56+/-12.2 years; male:female ratio, 2:1), 12 had pyrexia of unknown
origin and the other nine underwent evaluation for metastasis. The median lesion
size was 2.4*1.6 cm. Ten patients were diagnosed with tuberculosis (shown by the
presence of caseating granulomas [n=10] and acid-fast bacilli [n=4]). Two
patients had EUS-FNA results suggestive of histoplasmosis. The other patients had
metastatic lung carcinoma (n=6), hepatocellular carcinoma (n=1), and adrenal
lipoma (n=1) and adrenal myelolipoma (n=1). EUS results were not suggestive of
any particular etiology. No procedure-related adverse events occurred.
CONCLUSIONS: EUS-FNA is a safe and effective method for evaluating adrenal
masses, and it yields diagnosis in cases where tissue diagnosis is impossible or
has failed using conventional imaging modalities.
PMID- 25844347
TI - Peripheral facial nerve palsy after therapeutic endoscopy.
AB - Peripheral facial nerve palsy (FNP) is a mononeuropathy that affects the
peripheral part of the facial nerve. Primary causes of peripheral FNP remain
largely unknown, but detectable causes include systemic infections (viral and
others), trauma, ischemia, tumor, and extrinsic compression. Peripheral FNP in
relation to extrinsic compression has rarely been described in case reports.
Here, we report a case of a 71-year-old man who was diagnosed with peripheral FNP
following endoscopic submucosal dissection. This case is the first report of the
development of peripheral FNP in a patient undergoing therapeutic endoscopy. We
emphasize the fact that physicians should be attentive to the development of
peripheral FNP following therapeutic endoscopy.
PMID- 25844348
TI - Eosinophilic gastroenteritis due to rhus ingestion presenting with
gastrointestinal hemorrhage.
AB - Rhus-related illnesses in Korea are mostly caused by ingestion of parts of the
Rhus tree. Contact dermatitis occurrence after ingestion of Rhus-related food is
very common in Korea. However, Rhus-related gastrointestinal disease is very
rare. Herein, we present a case of eosinophilic gastroenteritis caused by Rhus
ingestion. A 75-year-old woman was admitted with hematemesis and hematochezia
after Rhus extract ingestion. Routine laboratory tests revealed leukocytosis
without eosinophilia. Endoscopy showed friable and granular mucosal changes with
touch bleeding in the second portion of the duodenum. Abdominal computed
tomography revealed edematous wall thickening of the duodenum and proximal
jejunal loops. Patch testing with Rhus extracts showed a strong positive
reaction, suggesting Rhus as the allergen. Her symptoms improved after avoidance
of the allergen.
PMID- 25844349
TI - "Cat scratch colon" in a patient with ischemic colitis.
AB - "Cat scratch colon" is a gross finding characterized by hemorrhagic mucosal
scratches on colonoscopy. It is usually associated with a normal colon and is
rarely associated with collagenous colitis. In a previous report, cat scratch
colon was noted in the cecum and ascending colon, but has also been observed in
the distal transverse colon. The patient in this study was also diagnosed with
ischemic colitis that may have played a role in the development of cat scratch
colon.
PMID- 25844350
TI - Imaging Vascular Disease and Amyloid in the Aging Brain: Implications for
Treatment.
AB - Vascular risk factors (e.g. hypertension, dyslipidemia and diabetes) are well
known risk factors for Alzheimer' disease. These vascular risk factors lead to
vascular brain injuries, which also increase the likelihood of dementia. The
advent of amyloid PET imaging has helped establish that vascular risk factors
also lead to Alzheimer's disease via pathways that are independent from vascular
brain injuries, at least, when vascular brain injuries are measured as white
matter lesions and infarcts. While vascular brain injuries (white matter lesions
and infarcts) do not seem to influence amyloid pathology, some evidence from
amyloid imaging suggests that increased vascular risk is related to increased
amyloid burden. Furthermore, while vascular brain injuries and amyloid have an
additive and independent impact on brain integrity, vascular risk factors might
potentiate the impact of amyloid on cortical thickness on brain regions
vulnerable to Alzheimer's disease. New research should further explore and
confirm, or refute, possible interactions between amyloid and vascular risk
factors on brain integrity and cognition. Neuroimaging tools used to assess
vascular brain integrity should also be expanded. Measuring cortical blood flow
or damage to the capillary system might, for instance, give insight about how
vascular risk factors can be associated to amyloid burden and impact. These
findings also stress the need for monitoring vascular risk factors in midlife as
a strategy for Alzheimer's disease prevention.
PMID- 25844351
TI - Feasibility of implementing a surgical student internship program in South Korea.
AB - PURPOSE: Despite recommendations for introducing student internships (SI) in
undergraduate medical education in Korea, the feasibility of surgical SIs has not
been demonstrated in the Korean context. We thus identified tasks that could be
performed by surgical student interns in a Korean education hospital. METHODS:
The opinions of surgery clerkship directors of medical schools nationwide,
regarding the tasks, symptoms and signs, disease entities, and procedures that
student interns could perform in their hospitals, were subjected to descriptive
analysis. RESULTS: Out of the 41 medical schools in Korea, 32 responded. Five
implemented an optimal-quality SI program. Two schools considered third-year
clerkship as SI. The respondents replied that student interns could be involved
in basic nonspecific tasks such as history taking, physical examination, medial
recording, reporting patients' status, and assisting during surgery. However,
more surgery-specific tasks such as perioperative management or caring for a
patient with acute abdominal pain were considered difficult for student interns
to encounter in the Korean context. CONCLUSION: Surgical educators should
determine a specific role for student interns and encourage them to perform
surgery-specific tasks. We recommend societal and system support, and curriculum
renovation to establish an SI program in Korea.
PMID- 25844352
TI - The neutrophil to lymphocyte ratio can discriminate anaplastic thyroid cancer
against poorly or well differentiated cancer.
AB - PURPOSE: We evaluated the capability of the neutrophil to lymphocyte ratio (NLR)
as a diagnostic tool to discriminate between poorly differentiated thyroid cancer
(PDTC) and anaplastic thyroid cancer (ATC) from well differentiated thyroid
cancer (WDTC). METHODS: The NLR of 3,870 patients with benign and malignant
thyroid tumors were analyzed. There were 436 benign, 3,364 papillary, 15
medullary, 34 follicular or hurthle type, 14 PDTC, and 7 ATC type neoplasms.
Patients were divided into two groups: a high NLR group and a low NLR group.
RESULTS: The NLR of all 3,870 patients was a normal distribution, and the median
value was 1.57. Advanced stage cancer, such as T3 or T4 was high (30.4% vs.
26.5%, P = 0.027), and cancer-specific deaths were also high (1.2% vs. 0.4%, P =
0.018) in the high NLR group. The proportion of PDTC (0.6% vs. 0.1%) and ATC
(0.3% vs. 0.1%) was higher in the high NLR group. The NLR can discriminate
between PTC, PDTC, and ATC (P = 0.035, P = 0.002, and P = 0.025, respectively),
and the cutoff value was 3.8 between PDTC versus ATC. None of the NLR of PDTC
exceeded the cutoff value of 3.8. CONCLUSION: NLR can play a relevant role as a
discriminating tool and may be considered as a new diagnostic criterion in
discriminating as well as in selecting therapeutic approaches to these aggressive
forms of thyroid cancer.
PMID- 25844353
TI - The benefits of preincision ropivacaine infiltration for reducing postoperative
pain after robotic bilateral axillo-breast approach thyroidectomy: a prospective,
randomized, double-blind, placebo-controlled study.
AB - PURPOSE: The aim of this study was to evaluate the effects of preoperative
ropivacaine infiltration in patients undergoing robotic thyroidectomy using the
bilateral axillary breast approach method. METHODS: Using a randomized, double
blind study design, 34 consecutive female patients who underwent robotic
thyroidectomy were randomly assigned to receive local infiltration to the skin
flap site using either only 0.9% saline solution, 3 mL/kg (group C, n = 17) or
0.1% ropivacaine with saline, 3 mg/kg (group L, n = 17). Local anesthetic was
administered prior to skin incision after the induction of general anesthesia.
Postoperative pain was rated at 2, 6, 18, 30, 42, and 66 hours postoperatively by
visual analogue scale (VAS) score. The bottom hit counts (BHC) from patient
controlled analgesia and fentanyl consumption were evaluated. CRP levels, mean
blood pressure (BP), and heart rate (HR) were also evaluated. RESULTS: VAS pain
scores were significantly lower in group L than in group C from 2 to 42 hours (P
< 0.05). Fentanyl use for analgesia and BHC were also significantly lower in
group L compared with group C during the first postoperative 6 and 2 hours,
respectively (P < 0.05). The total consumption of fentanyl was significantly
lower in group L than in group C (P = 0.009). No significant differences were
noted for baseline, postoperative mean BP, or HR. CONCLUSION: Preoperative
infiltration using ropivacaine with saline to all flap sites is a safe and
effective method for reducing postoperative pain and postoperative fentanyl
consumption in patients with robotic thyroidectomy.
PMID- 25844354
TI - Ki-67 and p53 expression as a predictive marker for early postoperative
recurrence in pancreatic head cancer.
AB - PURPOSE: This study aimed to evaluate the clinical significance of Ki-67 and p53
expressions in patients with pancreatic head cancer. METHODS: Between May 2008
and April 2013, immunohistochemical staining for Ki-67 and p53 was performed in
34 patients with pancreatic head cancer (ductal adenocarcinoma). All 34 patients
underwent pancreaticoduodenectomy at Chonnam National University Hwasun Hospital,
Hwasun, Korea. Clinical and histopathological characteristics were analyzed,
relative to p53 expression. RESULTS: Thirty (88.2%) and twenty-one (61.7%) of the
34 pancreatic head cancers exhibited positive expression of Ki-67 and p53,
respectively. Patients expressing Ki-67 and p53 experienced more frequent tumor
recurrences within 1 year after surgical resection (P = 0.003 and P = 0.030,
respectively). However, no correlation was detected between Ki-67 and p53
expression. Ki-67 expression was correlated with pathological grade, lymph node
metasatsis, and clinical stage (P < 0.05). Importantly, Ki-67 was the independent
predictive factor for postoperative recurrence within 1 year in both univariable
and multivariable analyses (odds ratio, 27.219; 95% confidence interval, 1.403
528.135; P = 0.029). CONCLUSION: The expression of Ki-67 and p53 are
significantly related to early postoperative recurrence within 1 year after
surgical resection in pancreatic head cancer. Especially, Ki-67 was the
independent predictive factor for postoperative recurrence within 1 year.
Therefore, immunohistochemical staining for Ki-67 and p53 may be applied as a
predictive marker for early postoperative recurrence in pancreatic head cancer.
PMID- 25844355
TI - Follow-up results of acute portal and splenic vein thrombosis with or without
anticoagulation therapy after hepatobiliary and pancreatic surgery.
AB - PURPOSE: Acute portal and splenic vein thrombosis (APSVT) after hepatobiliary and
pancreatic (HBP) surgery is a rare but serious complication and a treatment
strategy has not been well established. To assess the safety and efficacy of
anticoagulation therapy for treating APSVT after HBP surgery. METHODS: We
performed a retrospective case-control study of 82 patients who were diagnosed
with APSVT within 4 weeks after HBP surgery from October 2002 to November 2012 at
a single institute. We assigned patients to the anticoagulation group (n = 32) or
nonanticoagulation group (n = 50) and compared patient characteristics,
complications, and the recanalization rate of APSVT between these two groups.
RESULTS: APSVT was diagnosed a mean of 8.6 +/- 4.8 days after HBP surgery.
Patients' characteristics were not significantly different between the two
groups. There were no bleeding complications related to anticoagulation therapy.
The 1-year cumulative recanalization rate of anticoagulation group and
nonanticoagulation group were 71.4% and 34.1%, respectively, which is
statistically significant (log-rank test, P = 0.0001). In Cox regression model
for multivariate analysis, independent factors associated with the recanalization
rate of APSVT after HBP surgery were anticoagulation therapy (P = 0.003; hazard
ration [HR], 2.364; 95% confidence interval [CI], 1.341-4.168), the absence of a
vein reconstruction procedure (P = 0.027; HR, 2.557; 95% CI, 1.111-5.885), and
operation type (liver resection rather than pancreatic resection; P = 0.005, HR,
2.350; 95% CI, 1.286-4.296). CONCLUSION: Anticoagulation therapy appears to be a
safe and effective treatment for patients with APSVT after HBP surgery. Further
prospective studies of larger patient populations are necessary to confirm our
findings.
PMID- 25844356
TI - The effect of long Roux-en-Y gastrojejunostomy in gastric cancer patients with
type 2 diabetes and body mass index < 35 kg/m(2): preliminary results.
AB - PURPOSE: We applied a long Roux-en-Y (RY) gastrojejunostomy (bypassed jejunum
over 100 cm) as a reconstruction method for diabetes control to gastric cancer
patients with type 2 diabetes and body mass index (BMI) < 35 kg/m(2). The effect
of this procedure on diabetes control was assessed. METHODS: We prospectively
performed modified RY gastrojejunostmy after curative radical distal gastrectomy.
Thirty patients had completed a 1-year follow-up. Patients were followed
concerning their diabetic status. The factors included in the investigation were
length of bypassed jejunum, BMI and its reduction ratio, glycated hemoglobin
(HbA1c), fasting blood glucose, and duration of diabetes. Diabetic status after
surgery was assessed in three categories: remission, improvement, and stationary.
In evaluation of surgical effects on diabetes control, remission and improvement
groups were regarded as effective groups, while stationary was regarded as an
ineffective group. RESULTS: At postoperative one year, statistical significance
was observed in the mean BMI and HbA1c. Diabetes control was achieved in 50% of
the patients (remission, 30%; improvement, 20%). BMI reduction ratio,
preoperative HbA1c, and duration of diabetes were correlated to the status of
type 2 diabetes mellitus. The preoperative HbA1c was the most influential
predictor in diabetic control. CONCLUSION: The effect of long RY
gastrojejunostomy after gastrectomy for diabetes control could be contentious but
an applicable reconstruction method for diabetes control in gastric cancer
patients with type 2 diabetes and BMI < 35 kg/m(2). Diabetes remission is
expected to be higher in patients with greater BMI reduction, short duration of
diabetes, and lower preoperative HbA1c.
PMID- 25844357
TI - De novo malignancy after liver transplantation: a single-center experience of 14
cases.
AB - PURPOSE: The aim of this study is to evaluate the incidence of de novo malignancy
after liver transplantation (LT) and compare with those among the general Chinese
population. METHODS: A total of 466 patients who had a minimum follow-up time of
6 months were enrolled in the study. All data of medical records and follow up
were retrospectively reviewed. RESULTS: The incidence rate of de novo malignancy
was 3.0% (14 in 466 patients). The median elapsed time from transplant to the
diagnosis of de novo malignancy was 42 months (range, 6 to 106 months). The
cumulative risk for development of de novo malignancy was 1.6%, 2.7%, and 8.2% at
3, 5 and 10 years after LT, respectively. The patients were all male. The types
of de novo tumors included digestive system tumor (8 in 14), lung cancer (2 in
14), urologic neoplasm (2 in 14), and hematologic malignant tumor (2 in 14). Over
a mean follow-up of 24 months after diagnosis of de novo malignancy, 7 patients
(50.0%) died; the overall 5-year patient survival rate was 54.5%. The relative
risk of malignancy following LT was 9.5 folds higher than the general Chinese
population. CONCLUSION: The relative risk of malignancy following LT was much
higher than the general Chinese population. Digestive system tumor is the most
common type of de novo malignancy after LT in China.
PMID- 25844358
TI - Double common bile duct with an ectopic drainage into the stomach.
AB - Double common bile duct (DCBD) is a rare congenital anomaly among biliary
anomalies. The anomaly has an important clinical implication because of its
association with anomalous pancreaticobiliary ductal union (APBDU) and upper
gastrointestinal cancers. In addition, if one of the two common bile ducts is
mistaken for the cystic duct during surgery, bile duct injury is likely to occur.
Treatment depends on the coexistence of concomitant cancer and APBDU. A 54-year
old male diagnosed of gastric cancer was referred for surgery. During surgery, we
incidentally detected bile leak from the tubular structure around the
hepatoduodenal ligament. We performed intraoperative cholangiogram by cannulizing
into the tubular structure, and confirmed the tubular duct as the accessory bile
duct with an ectopic drainage into the stomach, which was connected to the
proximal common bile duct. In this study, we report a rare case of DCBD with an
ectopic drainage into the stomach and review the literature.
PMID- 25844359
TI - Experience of direct percutaneous sac injection in type II endoleak using cone
beam computed tomography.
AB - Cone beam CT, usually used in dental area, could easily obtain 3-dimensional
images using cone beam shaped ionized radiation. Cone beam CT is very useful for
direct percutaneous sac injection (DPSI) which needs very precise measurement to
avoid puncture of inferior vena cava or vessel around sac or stent graft. Here we
describe two cases of DPSI using cone beam CT. In case 1, a 79-year-old male had
widening of preexisted type II endoleak after endovascular aneurysm repair
(EVAR). However, transarterial embolization failed due to tortuous collateral
branches of lumbar arteries. In case 2, a 72-year-old female had symptomatic sac
enlargement by type II endoleak after EVAR. However, there was no route to
approach the lumbar arteries. Therefore, we performed DPSI assisted by cone beam
CT in cases 1, 2. Six-month CT follow-up revealed no sign of sac enlargement by
type II endoleak.
PMID- 25844360
TI - Transanal gauze packing to manage massive presacral bleeding secondary to
prescral abscess caused by rectal anastomotic leakage: a novel approach.
AB - Anastomotic leakage following rectal resection is a serious and fearful
complication, and may cause presacral abscess and/or peritonitis. To our
knowledge, massive hematochezia secondary to presacral abscess caused by
anastomotic leakage has not yet been reported in the literature. We observed this
rare and life-threatening complication in three patients who were successfully
treated with a simple but effective transanal gauze packing technique.
PMID- 25844361
TI - Providing optimal regional care for ST-segment elevation myocardial infarction: a
prospective cohort study of patients in the Hamilton Niagara Haldimand Brant
Local Health Integration Network.
AB - BACKGROUND: Although considered the evidence-based best therapy for ST-segment
elevation myocardial infarction (STEMI), many patients do not receive primary
percutaneous coronary intervention (PCI) because of health care resource
distribution and constraints. This study describes the clinical management and
outcomes of all patients identified with STEMI within a region, including those
who did not receive primary PCI. METHODS: This study used a prospective cohort
design. Patients presenting with STEMI to PCI- and non-PCI-capable hospitals in
one integrated health region in Ontario were included in the study. The primary
objective was to examine use of reperfusion strategies and timeliness of care.
Secondary objectives included determining (through regression models) which
variables were associated with mortality within 90 days, and describing patient
uptake of risk-reducing therapies and activities post-STEMI. RESULTS: Between
Apr. 1, 2010, and Mar. 31, 2013, data were collected on 2247 consecutive patients
presenting with STEMI. Patients presenting to the PCI-capable hospital were more
likely to receive primary PCI (82.5% v. 65.2%, p < 0.001) and be treated within
optimal treatment times. However, there was no appreciable difference in
mortality at 90 days post-STEMI between patients presenting to PCI- and non-PCI
capable hospitals (7.8% v. 7.5%, p = 0.82), even after adjustment for acuity on
presentation. Despite recognized risk factors, many patients were not taking
evidence-based medications for risk factor modification before STEMI.
INTERPRETATION: A systematic approach to regional STEMI care focusing on timely
access to the best available therapies, rather than the type of reperfusion
provided alone, can yield favourable outcomes.
PMID- 25844362
TI - The effect of pharmacist-led medication review in high-risk patients in the
emergency department: an evaluation protocol.
AB - BACKGROUND: Adverse drug events are unintended and harmful events related to
medication use. They are a leading cause of visits to the emergency department,
unplanned admissions to hospital and death. Adverse drug events can be
misdiagnosed in the emergency department, resulting in treatment delays. Our
objective was to describe a process to evaluate the effect of pharmacist-led
medication review in high-risk patients in the emergency department on the number
of days these patients subsequently spent in hospital within 30 days of their
index visit. METHODS: We describe the evaluation of a prospective multicentre
quality improvement program. During the evaluation period, triage nurses will
flag incoming patients to the emergency department at high risk for adverse drug
events by applying a clinical decision rule consisting of 4 variables (comorbid
conditions, antibiotic use within 7 days, medication changes within 28 days and
age). Consecutive eligible patients will be enrolled in the study and
systematically allocated to either a pharmacist-led medication review group or a
control group. In the intervention group, pharmacists will collect best-possible
medication histories, review the patient's medications for appropriateness and
adverse drug events, and communicate the results of their medication review to
patients, caregivers and physicians. In the control group, nurses will start
medication reconciliation by collecting best-possible medication histories, and
physicians will refer patients to onsite pharmacists for specific medication
management questions as needed. Health outcomes will be assessed using anonymized
data linkage to administrative health databases. The primary outcome will be the
percent days spent in hospital over a 30-day period. INTERPRETATION: This
protocol describes the methods for evaluating the effect of pharmacist-led
medication review in high-risk patients in the emergency department on use of
health services, and highlights the methodological challenges that will be
encountered. We plan to disseminate the results of this evaluation through
articles published in peer-reviewed journals, presentations at scientific
meetings and briefing notes to institutional, provincial and national
stakeholders.
PMID- 25844363
TI - Patterns of health care use in a high-cost inpatient population in Ottawa,
Ontario: a retrospective observational study.
AB - BACKGROUND: A small proportion of patients account for the majority of health
care spending. We used detailed clinical and administrative data to explore
clinical characteristics, patterns of health care use and changes in cost
profiles over time among high-cost inpatients in an acute tertiary care hospital
in Ottawa, Ontario. METHODS: We identified all people who had 1 or more inpatient
admissions to The Ottawa Hospital between Apr. 1, 2009, and Mar. 31, 2012. We
calculated the direct inpatient costs using case-costing information to
categorize patients into persistently high-cost, episodic high-cost and non-high
cost groups. Within each group, we used discharge abstracts to measure encounter
level characteristics and patterns of inpatient health care use over time. We
also developed transition matrices to explore how inpatient costing states
changed over time. RESULTS: During the study period, 100 178 patients had 132 996
hospital admissions. Hospital spending was often limited to a single year for
most of the patients (90.2%), with only a small proportion (7.4%) of patients
remaining in the high-cost group in the subsequent year. Patients in the
persistently (n = 236) and episodic (n = 5062) high-cost groups were often older,
had medically complex conditions and generated most of the costs from nursing
care and intensive care. Compared with patients in the other cost groups, those
in the persistently high-cost group were more likely to have multiple
readmissions (43.4%) and multiple placements in an alternate level of care
(19.0%) and were high users of health care services outside of the hospital
setting. INTERPRETATION: Hospital spending was often limited to a single year for
most patients, and only a small proportion of patients remained in the high-cost
group in the subsequent year. These persistently high-cost patients had medically
complex conditions and often required expensive care. A greater understanding of
the circumstances that result in persistent hospital spending remains an area for
future work, including an exploration of the potential barriers impeding
efficient transition out of acute care for high-risk patients.
PMID- 25844364
TI - Dermatoses among returned Canadian travellers and immigrants: surveillance report
based on CanTravNet data, 2009-2012.
AB - BACKGROUND: There is a lack of multicentre analyses of the spectrum of
dermatologic illnesses acquired by Canadian travellers and immigrants. Our
objective for this study was to provide a comprehensive, Canada-specific
surveillance summary of travel-related dermatologic conditions in a cohort of
returned Canadian travellers and immigrants. METHODS: Data for Canadian
travellers and immigrants with a primary dermatologic diagnosis presenting to
CanTravNet sites between September 2009 and September 2012 were extracted and
analyzed. Data were collected using the GeoSentinel data platform. This network
comprises 56 specialized travel and tropical medicine clinics, including 6
Canadian sites (Vancouver, Calgary, Toronto, Ottawa and Montreal), that
contribute anonymous, de-linked, clinician- and questionnaire-based travel
surveillance data on all ill travellers examined to a centralized Structure Query
Language database. Results were analyzed according to reason for most recent
ravel: immigration (including refugee); tourism; business;
missionary/volunteer/research and aid work; visiting friends and relatives; and
other, which included students, military personnel and medical tourists. RESULTS:
During the study period, 6639 patients presented to CanTravNet sites across
Canada and 1076 (16.2%) received a travel-related primary dermatologic diagnosis.
Arthropod bites (n = 162, 21.5%), rash (n = 141, 18.7%), cutaneous larva migrans
(n = 98, 13.0%), and skin and soft tissue infection (n = 92, 12.2%) were the most
common dermatologic diagnoses or diagnostic bundles issued to returning Canadian
tourists (n = 754, 70.1% of total sample). Patients travelling for the purpose of
immigration (n = 63, 5.9%) were significantly more likely to require inpatient
management of their dermatologic diagnoses (p < 0.001) than those travelling for
other purposes. INTERPRETATION: This analysis of surveillance data details the
spectrum of travel-related dermatological conditions among returning Canadian
travellers in this cohort, and provides an epidemiologic framework for Canadian
physicians encountering these patients.
PMID- 25844365
TI - The development of guideline implementation tools: a qualitative study.
AB - BACKGROUND: Research shows that guidelines featuring implementation tools
(GItools) are more likely to be used than those without GItools, however few
guidelines offer GItools and guidance on developing GItools is lacking. The
objective of this study was to identify common processes and considerations for
developing GItools. METHODS: Interviews were conducted with developers of 4 types
of GItools (implementation, patient engagement, point-of-care decision-making and
evaluation) accompanying guidelines on various topics created in 2008 or later
identified in the National Guideline Clearinghouse. Participants were asked to
describe the GItool development process and related considerations. A descriptive
qualitative approach was used to collect and analyze data. RESULTS: Interviews
were conducted with 26 GItool developers in 9 countries. Participants largely
agreed on 11 broad steps, each with several tasks and considerations. Response
variations identified issues lacking uniform approaches that may require further
research including timing of GItool development relative to guideline
development; decisions about GItool type, format and content; and whether and how
to engage stakeholders. Although developers possessed few dedicated resources,
they relied on partnerships to develop, implement and evaluate GItools.
INTERPRETATION: GItool developers employed fairly uniform and rigorous processes
for developing GItools. By supporting GItool development, the GItool methods
identified here may improve guideline implementation and use.
PMID- 25844366
TI - Chronic obstructive pulmonary disease in primary care: an epidemiologic cohort
study from the Canadian Primary Care Sentinel Surveillance Network.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is mostly managed within
primary care, but there is little Canadian evidence from this setting. This study
was undertaken to determine the prevalence of physician-diagnosed COPD in primary
care practices, and the degree of comorbidity with other chronic conditions, and
to assess patterns of medication prescribing. METHODS: The Canadian Primary Care
Sentinel Surveillance Network is a national "network of networks" whose member
practices use electronic medical records (EMRs). At the time of the study, it
included data from 444 physicians from 10 networks in 8 provinces. We conducted
an epidemiologic cohort study of all patients who had EMR data collected by the
network at the end of 2012. Validated case-finding algorithms were used to
identify cases of COPD. We used descriptive statistics and multivariate modelling
analyses to calculate the prevalence of COPD, its association with key
demographic factors and comorbidities, and patterns of medication prescribing.
RESULTS: The observed prevalence of COPD was 4.0% (10 043/250 346), which
represents a population prevalence of 3.4% using age-sex standardization.
Comorbidity was common, with prevalence ratios ranging from 1.1 for the presence
of a single comorbid condition to 1.9 for 4 or more comorbid conditions.
Anticholinergic agents (63%), short- (48%) and long-acting (38%) beta-agonists
and inhaled corticosteroids (41%) were the most commonly used medications.
INTERPRETATION: The prevalence of physician-diagnosed COPD in Canadian primary
care practices was similar to that reported in other practice-based studies at
about 3%-4%. Most patients had comorbid conditions and were taking multiple
medications. EMR data may be useful to assess both the epidemiology and
management of COPD in primary care practices.
PMID- 25844367
TI - Prevention of overweight and obesity in children and youth: a systematic review
and meta-analysis.
AB - BACKGROUND: One-third of Canadian children are overweight or obese. This problem
carries considerable concern for negative impacts on current and future health.
Promoting healthy growth and development is critical. This review synthesized
evidence on the effectiveness of behavioural interventions for preventing
overweight and obesity in children and adolescents. METHODS: We updated the
search of a previous Cochrane review. Five databases were searched up to August
2013. Randomized trials of primary care-relevant behavioural (diet, exercise and
lifestyle) interventions for preventing overweight and obesity in healthy normal-
or mixed-weight children or youth aged 0-18 years were included if 12-week
postbaseline data were provided for body mass index (BMI), BMI z-score, or
prevalence of overweight or obesity. Any study reporting harms was included. Meta
analyses were performed if possible. Features of interventions showing
significant benefits were examined. RESULTS: Ninety studies were included, all
with mixed-weight populations. Compared with controls, interventions showed a
small but significant effect on BMI and BMI z-score (standardized mean difference
-0.07, 95% confidence interval [CI] -0.10 to -0.03, I (2) = 74%), a reduction in
BMI (mean difference -0.09 kg/m(2), 95% CI -0.16 to -0.03, I (2) = 76%) and a
reduced prevalence of overweight and obesity (risk ratio [RR]; RRintervention -
RRcontrol 0.94, 95% CI 0.89 to 0.99, I (2) = 0%; number needed to treat 51, 95%
CI 29 to 289). Little evidence was available on harms. There was variability
across efficacious interventions, although many of the interventions were short
term, involved school-aged children and were delivered in educational settings.
INTERPRETATION: Behavioural prevention interventions are associated with small
improvements in weight outcomes in mixed-weight populations of children and
adolescents. No intervention strategy consistently produced benefits.
REGISTRATION: PROSPERO no. CRD42012002754.
PMID- 25844368
TI - Treatment of overweight and obesity in children and youth: a systematic review
and meta-analysis.
AB - BACKGROUND: Childhood obesity is a public health concern. One-third of North
American children and youth are overweight or obese. We reviewed the evidence of
behavioural and pharmacological weight-management interventions on body mass
index (BMI), BMI z-score and the prevalence of overweight and obesity in children
and youth. METHODS: We updated the search of a previous review. We searched 4
databases up to August 2013. We included randomized trials of primary care
relevant behavioural (diet, exercise, lifestyle) and pharmacological (orlistat)
interventions for treating overweight and obesity in children and youth aged 2-18
years if 6-month post-baseline data were provided for BMI, BMI z-score or
prevalence of overweight and obesity. In addition, we examined secondary health
outcomes such as lipid and glucose levels, blood pressure, quality of life and
physical fitness. We included any study reporting harms. We performed meta
analyses when possible, and we examined the features of interventions that showed
benefits. RESULTS: Thirty-one studies (29 behavioural, 2 pharmacological and
behavioural) were included. Both intervention types showed a significant effect
on BMI or BMI z-score in favour of treatment (behavioural: standardized mean
difference [SMD] -0.54, 95% confidence interval [CI] -0.73 to -0.36; orlistat
plus behavioural: SMD -0.43, 95% CI -0.60 to -0.25). Studies reported no
significant difference between groups in the likelihood of reduced prevalence of
overweight or overweight and obesity. Pooled estimates for blood pressure and
quality of life showed significant benefits in favour of treatment (systolic
blood pressure mean difference [MD] -3.42, 95% CI -6.65 to -0.29; diastolic blood
pressure MD -3.39, 95% CI -5.17 to -1.60; quality of life MD 2.10, 95% CI 0.60 to
3.60). Gastrointestinal difficulties were more common in youth taking orlistat
than in the control group (risk ratio 3.77, 95% CI 2.56 to 5.55). We saw much
variability across efficacious interventions. INTERPRETATION: Low- to moderate
quality evidence suggests behavioural treatments are associated with a medium
effect in terms of reduced BMI or BMI z-score compared with a small effect shown
by combined pharmacological-behavioural interventions. Future research should
evaluate active weight maintenance interventions in adolescents with longer
follow-up and examine the effectiveness of combined pharmacological and
behavioural interventions. REGISTRATION: PROSPERO no. CRD42012002754.
PMID- 25844369
TI - Strategies for weight maintenance in adult populations treated for overweight and
obesity: a systematic review and meta-analysis.
AB - BACKGROUND: Once weight loss is achieved, the challenge is to maintain this
benefit. This review reports on the effectiveness of programs for weight-loss
maintenance, as part of a larger review examining treatments for overweight and
obese adults. METHODS: We updated the search of a 2011 review on screening and
management of overweight and obese adults. Four databases were searched. For
inclusion, participants had to have lost weight in treatment and then been
randomly assigned to a weight-maintenance intervention or control conditions.
Studies from the 2011 review that met the criteria were included. Data were
extracted and pooled (where possible) for outcomes related to weight-loss
maintenance. RESULTS: Eight studies were included. Compared with control
participants, intervention participants regained less weight (mean difference
[MD] -1.44 kg, 95% confidence interval [CI] -2.42 to -0.47), regardless of
whether the intervention was behavioural (MD-1.56 kg, 95% CI -3.10 to -0.02) or
pharmacologic plus behavioural (MD -1.39 kg, 95% CI -2.86 to 0.08). Intervention
participants also showed better weight maintenance than the control participants
in terms of waist circumference (MD -2.30 cm, 95% CI -3.45 to -1.15) and body
mass index (MD -0.95 kg/m(2), 95% CI -1.67 to -0.23). Participants undergoing
pharmacologic plus behavioural interventions were more likely to maintain a loss
of 5% or more of initial body weight than those in the control group (risk ratio
[RR] 1.33, 95% CI 1.15 to 1.54); no difference was found for maintaining a weight
loss of 10% or more (RR 1.76, 95% CI 0.75 to 4.12). INTERPRETATION: Moderate
quality evidence shows that overweight and obese adults can benefit from
interventions for weight maintenance following weight loss. However, there is
insufficient evidence on the long-term sustainability of these benefits.
REGISTRATION: PROSPERO no. CRD42012002753.
PMID- 25844370
TI - Neonatal opioid withdrawal and antenatal opioid prescribing.
AB - BACKGROUND: The incidence of neonatal opioid withdrawal is increasing in both
Canada and the United States. However, the degree to which the treatment of pain
with opioids, rather than the misuse of prescription opioids or heroin,
contributes to the prevalence of neonatal opioid withdrawal remains unknown.
METHODS: We conducted a retrospective, population-based, cross-sectional study
between 1992 and 2011 in Ontario with 2 objectives. First, we determined the
annual incidence of neonatal abstinence syndrome. Second, using data from a
subset of women eligible for publicly funded prescription drugs, we determined
what proportion of women who deliver an infant with neonatal abstinence syndrome
were given a prescription for an opioid before and during pregnancy. RESULTS: The
incidence of neonatal abstinence syndrome in Ontario increased 15-fold during the
study period, from 0.28 per 1000 live births in 1992 to 4.29 per 1000 live births
in 2011. During the final 5 years of the study, we identified 927 deliveries of
infants with neonatal abstinence syndrome to mothers who were public drug plan
beneficiaries. Of these mothers, 67% had received an opioid prescription in the
100 days preceding delivery, including 53.3% who received methadone, an increase
from 28.6% in the interval spanning 1 to 2 years before delivery (p < 0.001).
Prescription for nonmethadone opioids decreased from 38% to 17% (p < 0.001).
INTERPRETATION: The incidence of neonatal opioid withdrawal in Ontario has
increased substantially over the last 20 years. Most of the women in this cohort
who delivered an infant with neonatal abstinence syndrome had received a
prescription for an opioid both before and during their pregnancy.
PMID- 25844371
TI - Acceptability and yield of birth-cohort screening for hepatitis C virus in a
Canadian population being screened for colorectal cancer: a cross-sectional
study.
AB - BACKGROUND: Screening for hepatitis C virus (HCV) is recommended in patients born
between 1945 and 1965 ("baby boomers") in the United States. Because these
patients are often screened for colorectal cancer, dual screening for HCV may
enhance case identification. Our objectives were to assess the acceptability and
yield of screening for HCV among patients undergoing screening for colorectal
cancer. METHODS: Patients referred for a colonoscopy to screen for colorectal
cancer completed an anonymous survey regarding the acceptability of screening for
HCV, risk factors and prior testing. The impacts of demographics and risk factors
for HCV on willingness to be screened were determined using logistic regression,
and the stored sera of 483 patients who had undergone screening for colorectal
cancer between February 2011 and August 2012 were tested for HCV antibodies.
RESULTS: Among 1012 survey respondents (median age 56 yr; 911 [90.0%] were baby
boomers, 880 [87.0%] were white and 223 [22.0%] were born outside Canada), 123
patients (12.2%) reported prior testing for HCV. HCV was previously diagnosed in
9 of these patients (0.9%, representing 1.0% of the patients who were baby
boomers): 5 (55.6% of those diagnosed) reported risk factors. Excluding patients
diagnosed with HCV, 903 (90.0%) respondents indicated that they would consent to
testing of blood or saliva for HCV. After adjusting for age, sex and status of
immigration, patients who were white (odds ratio [OR] 3.38, 95% confidence
interval [CI] 1.81-6.32) and patients with risk factors (> 1 v. 0: OR 3.67, 95%
CI 1.12-12.02) had a greater acceptance of screening. Among 483 patients screened
for colorectal cancer, 3 were anti-HCV positive (0.6%, 95% CI 0.1%-1.8%),
representing 0.8% (95% CI 0.2%-2.4%) of the patients who were baby boomers.
INTERPRETATION: Acceptance of screening for HCV is high among patients undergoing
screening for colorectal cancer in the Calgary area. However, the low prevalence
of HCV suggests that the cost-effectiveness of birth-cohort screening in this
population warrants evaluation.
PMID- 25844372
TI - Effect of pediatric palliative care programs on health care resource utilization
and costs among children with life-threatening conditions: a systematic review of
comparative studies.
AB - BACKGROUND: Pediatric palliative care is a relatively new and evolving field, and
the cost of pediatric palliative care programs is unclear. We conducted a
systematic review to compare inpatient health care utilization and costs among
children with life-threatening conditions who have accessed a pediatric
palliative care program and those who have not. METHODS: We searched MEDLINE,
Embase, CINAHL and LILACS databases from January 2000 to July 2013, as well as
the grey literature, for experimental or observational studies that compared
pediatric palliative care programs with usual care. Outcomes of interest included
hospital admissions, length of stay and health care costs. RESULTS: Of the 5193
records identified, we reviewed 109 in full and included 11 in our study. The
overall quality of the studies was moderate to low. We observed mixed results for
all outcomes. Compared with patients receiving usual care, fewer patients in the
palliative care group had hospital admissions and fewer of those with cancer had
planned hospital admissions. In contrast, no effects were observed regarding the
overall number of hospital, emergency or outpatient admissions. Conflicting
results were observed with regards to critical care utilization. Studies showed a
trend toward shorter lengths of stay in hospital in the palliative care group.
However, a single study that also considered inpatient time in hospice facilities
found an increase in total length of stay, which showed a shift in the setting of
health care utilization. We observed no conclusive trend in the effects on cost.
INTERPRETATION: Evidence suggests that pediatric palliative care programs may
result in a shift of utilization to other health care settings beyond hospital
care. These settings should be considered when measuring resource utilization and
costs.
PMID- 25844373
TI - Prevalence and management of hypertension in primary care practices with
electronic medical records: a report from the Canadian Primary Care Sentinel
Surveillance Network.
AB - BACKGROUND: Most epidemiologic reports on hypertension in Canada are based on
data from surveys or on administrative data. We report on the prevalence and
management of hypertension based on data from the Canadian Primary Care Sentinel
Surveillance Network (CPCSSN), which consists of validated, national, point-of
care data from primary care practices. METHODS: We included CPCSSN data as of
Dec. 31, 2012, for patients 18 years and older who had at least 1 clinical
encounter during the previous 2 years with one of the 444 family physicians and
nurse-practitioners who participate in the CPCSSN. We calculated the prevalence
of hypertension, the proportion of patients who achieved blood pressure targets,
the number of encounters with primary care providers, comorbidities and
pharmacologic management. RESULTS: Of the 250 346 patients who met the
eligibility criteria, 57 180 (22.8%) had a diagnosis of hypertension. Of the 44
981 patients for whom blood pressure data were available, 35 094 (78.0%) had
achieved both targets for systolic (<=?140 mm Hg) and diastolic (<=?90 mm Hg)
pressure. Compared with patients who did not have a hypertension diagnosis, those
with hypertension were significantly more likely to have a comorbidity and
visited their primary care provider more often. Among the patients with
hypertension, 12.1% were not taking antihypertensive medications; nearly two
thirds (61.7%) had their condition controlled with 1 or 2 drugs. INTERPRETATION:
The prevalence of hypertension based on CPCSSN data was similar to estimates from
the Canadian Health Measures Survey. Although achievement of blood pressure
targets was high, patients with hypertension had more comorbidities and saw their
primary care provider more often than those without hypertension.
PMID- 25844374
TI - Secular trends in end-stage renal disease requiring dialysis in Manitoba, Canada:
a population-based study.
AB - BACKGROUND: End-stage renal disease (ESRD) requiring dialysis is expensive and is
associated with disproportionately poor health outcomes and quality of life.
Understanding regional long-term secular trends in the incidence and prevalence
of dialysis will allow for the alignment of appropriate and efficient delivery of
care. The primary objective of this study was to describe long-term secular and
geographic trends in ESRD over a 22-year period in a single-provider Canadian
health care setting. METHODS: Using a previously validated case definition, we
described the annual incidence and prevalence of ESRD in Manitoba from 1989 to
2010, stratified by age, sex and geographic location within the province.
RESULTS: We searched more than 1.2 million records within the Manitoba Health
repository. We identified 9489 patients in the Manitoba Health Physician Claims
database with at least 1 claim for dialysis from 1989 through Mar. 31, 2010.
Using the case definition of any 2 dialysis treatment claims, the total annual
incidence of ESRD increased 2.5-fold from 15.8 to 40.2 per 100 000 during the
study period. Of note, the northern rural portions of the province saw a 12-fold
unadjusted increase in ESRD, from 8.1 per 100 000 in 1989 to 96.3 per 100 000 in
2009. INTERPRETATION: The incidence and prevalence of ESRD is increasing in
Manitoba, most notably in the north of the province. Innovative interventions,
such as primary screening and treatment initiatives, should specially target
northern rural regions.
PMID- 25844375
TI - Deaths from exposure to paramethoxymethamphetamine in Alberta and British
Columbia, Canada: a case series.
AB - BACKGROUND: Paramethoxymethamphetamine (PMMA) is a ring-substituted amphetamine
similar in structure to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"),
but substantially more toxic. We describe the clinical features of fatal
exposures in the provinces of Alberta and British Columbia, Canada. METHODS: We
conducted a retrospective case series on deaths in Alberta and BC between June
2011 and April 2012 for which forensic toxicologic analysis was positive for PMMA
and the drug was implicated as the primary toxic agent. Data collected included
patient demographics, exposure history, clinical features, investigations,
therapy provided and postmortem toxicologic findings. RESULTS: A total of 27 PMMA
associated deaths (20 in Alberta, 7 in BC) were reported in the 11-month period.
The median age was 24 (range 14-52) years, and 22 (81%) were male. Ten patients
were pronounced dead at the scene, and 17 died in hospital. The median time from
exposure to death was 17 (range 5-264) hours. The median first-recorded vital
signs (and ranges) were: heart rate 160 (86-201) beats/min, blood pressure 89/43
(69/30-162/83) mm Hg, respiratory rate 40 (26-48) breaths/min, oxygen saturation
81% (68%-100%) and temperature 39.4 degrees C (34-43.8 degrees C). Sixteen of the
17 people who died in hospital presented with clinical features consistent with
serotonin syndrome. End-organ dysfunction included hepatic (30%) and acute kidney
injury (85%), rhabdomyolysis (54%), coagulopathy (61%) and cardiac ischemia
(15%). Other drugs identified on toxicologic analysis were MDMA (n = 27), cocaine
or its metabolite benzoylecgonine (n = 14) and methamphetamine (n = 12).
INTERPRETATION: Exposure to PMMA was characterized by multiorgan dysfunction and
serotonin syndrome, followed by cardiovascular collapse. In addition to PMMA,
multiple synthetic amphetamines were present on toxicologic analysis. When
evaluating patients suspected of exposure to sympathomimetic drugs of abuse,
clinicians must anticipate multiple clinical effects from the increased release
of dopamine, serotonin, norepinephrine and other neurotransmitters.
PMID- 25844376
TI - Patterns of use for brand-name versus generic oral bisphosphonate drugs in
Ontario over a 13-year period: a descriptive study.
AB - BACKGROUND: Bisphosphonates are the first-line therapy for the treatment of
osteoporosis. In the province of Ontario, the Ontario Drug Benefit Program funds
medications for patients aged 65 years and older. The Ontario Drug Benefit
Program has a generic substitution policy that requires lower-cost generic drugs
to be dispensed when they are available. However, there is controversy
surrounding the efficacy and tolerability of generic bisphosphonates. The
objective of this study was to describe patterns in the use of brand-name versus
generic formulations when dispensing oral bisphosphonate over a 13-year period.
METHODS: We identified all osteoporotic preparations for alendronate and
risedronate that were dispensed through the Ontario Drug Benefit Program from
2001 to 2014. We stratified our sample into community-dwelling residents and
residents in long-term care facilities. The number of prescriptions dispensed per
month were plotted to illustrate trends over time. RESULTS: We found a rapid
switch from brand-name to generic bisphosphonate equivalents immediately after
the generic became available on the Ontario Drug Benefit formulary, with generics
accounting for > 88% of dispensed drug within 2 months. We also observed a
reduction in the number of generic drugs dispensed each time a new brand-name
alternative (e.g., monthly risedronate, weekly alendronate plus vitamin D) was
introduced to the formulary. The dispensing trends were similar in the community
and long-term care settings. INTERPRETATION: The Ontario Drug Benefit Program
generic substitution policy resulted in rapid uptake of generic oral
bisphosphonates among seniors in Ontario. However, there was a switch away from
generic medications to new brand-name alternatives whenever they were introduced
to the formulary. Therefore, some patients continued to use brand-name
bisphosphonate despite the availability of generic options.
PMID- 25844377
TI - Chronic health conditions reported by male inmates newly admitted to Canadian
federal penitentiaries.
AB - BACKGROUND: International health studies have shown that inmates have higher
rates of infectious diseases, chronic diseases and psychiatric disorders relative
to the general population. We conducted a systematic collection of data on
chronic physical health conditions reported by newly admitted inmates in Canadian
federal penitentiaries. METHODS: Over a 6-month period from April to September
2012, we collected and analyzed data from a standardized health interview
routinely conducted with consenting incoming male inmates (n = 2273). Prevalence
rates of health conditions were determined and disaggregated by age (< 50 yr and
>= 50 yr) and by Aboriginal status. RESULTS: The most common health conditions
reported by respondents were head injury (34.1%), back pain (19.3%), asthma
(14.7%) and hepatitis C virus (HCV) infection (9.4%). Rates of many health
conditions were higher among inmates 50 years of age or older than among younger
inmates. Compared with their non-Aboriginal counterparts, Aboriginal inmates had
higher rates of head injury and HCV infection. INTERPRETATION: Our study provides
a benchmark that can be used to examine health trends within Canada's federal
penitentiaries over time and points to subgroups of newly admitted inmates for
whom health services may need to be concentrated.
PMID- 25844378
TI - Stroke Recovery: Surprising Influences and Residual Consequences.
AB - There is startling individual variability in the degree to which people recover
from stroke, and the duration of time over which recovery of some symptoms occur.
There are a variety of mechanisms of recovery from stroke, which take place at
distinct time points after stroke and are influenced by different variables. We
review recent studies from our laboratory that unveil some surprising findings,
such as the role of education in chronic recovery. We also report data showing
that the consequences that most plague survivors of stroke and their caregivers
are not dependence in activities of daily living, but loss of more high level
functions, such as empathy or written language. These results have implications
for rehabilitation and management of stroke.
PMID- 25844379
TI - The experience of implementing the board of trustees' policy in teaching
hospitals in Iran: an example of health system decentralization.
AB - BACKGROUND: In 2004, the health system in Iran initiated an organizational reform
aiming to increase the autonomy of teaching hospitals and make them more
decentralized. The policy led to the formation of a board of trustees in each
hospital and significant modifications in hospitals' financing. Since the reform
aimed to improve its predecessor policy (implementation of hospital autonomy
began in 1995), it expected to increase user satisfaction, as well as enhance
effectiveness and efficiency of healthcare services in targeted hospitals.
However, such expectations were never realized. In this research, we explored the
perceptions and views of expert stakeholders as to why the board of trustees'
policy did not achieve its perceived objectives. METHODS: We conducted 47 semi
structured face-to-face interviews and two focus group discussions (involving 8
and 10 participants, respectively) with experts at high, middle, and low levels
of Iran's health system, using purposive and snowball sampling. We also collected
a comprehensive set of relevant documents. Interviews were transcribed verbatim
and analyzed thematically, following a mixed inductive-deductive approach.
RESULTS: Three main themes emerged from the analysis. The implementation approach
(including the processes, views about the policy and the links between the policy
components), using research evidence about the policy (local and global), and
policy context (health system structure, health insurers capacity, hospitals'
organization and capacity and actors' interrelationships) affected the policy
outcomes. Overall, the implementation of hospital decentralization policies in
Iran did not seem to achieve their intended targets as a result of assumed
failure to take full consideration of the above factors in policy implementation
into account. CONCLUSION: The implementation of the board of trustees' policy did
not achieve its desired goals in teaching hospitals in Iran. Similar
decentralization policies in the past and their outcomes were overlooked, while
the context was not prepared appropriately and key stakeholders, particularly the
government, did not support the decentralization of Iran's health system.
PMID- 25844380
TI - Why and how is compassion necessary to provide good quality healthcare?
AB - Recent disclosures of failures of care in the National Health Service (NHS) in
England have led to debates about compassion deficits disallowing health
professionals to provide high quality responsive care. While the link between
high quality care and compassion is often taken for granted, it is less obvious
how compassion - often originating in the individual's emotional response - can
become a moral sentiment and lead to developing a system of norms and values
underpinning ethics of care. In this editorial, I argue why and how compassion
might become a foundation of ethics guiding health professionals and a basis for
ethics of care in health service organisations. I conclude by discussing a recent
case of prominent healthcare failure in the NHS to highlight the relationship
between compassion as an aspect of professional ethics on the one hand, and
values and norms that institutions and specific policies promote on the other
hand.
PMID- 25844381
TI - Improving the world's health through the post-2015 development agenda:
perspectives from Rwanda.
AB - The world has made a great deal of progress through the Millennium Development
Goals (MDGs) to improve the health and well-being of people around the globe, but
there remains a long way to go. Here we provide reflections on Rwanda's
experience in working to meet the health-related targets of the MDGs. This
experience has informed our proposal of five guiding principles that may be
useful for countries to consider as the world sets and moves forward with the
post-2015 development agenda. These include: 1) advancing concrete and meaningful
equity agendas that drive the post-2015 goals; 2) ensuring that goals to meet
Universal Health Coverage (UHC) incorporate real efforts to focus on improving
quality and not only quantity of care; 3) bolstering education and the internal
research capacity within countries so that they can improve local evidence-based
policy-making; 4) promoting intersectoral collaboration to achieve goals, and 5)
improving collaborations between multilateral agencies - that are helping to
monitor and evaluate progress towards the goals that are set - and the countries
that are working to achieve improvements in health within their nation and across
the world.
PMID- 25844382
TI - Patients attitude towards surgeons attire in Our Lady of Lourdes Hospital
Drogheda.
AB - BACKGROUND: A doctor's competence and professionalism is often judged on the
basis of attire. Our Lady of Lourdes (OLOL) is a leading Irish hospital in the
implementation of Bare Below the Elbows (BBTE) policy, however surgical attire is
not standardised and there is great variability in attire worn on wards. We aimed
to evaluate patients attitude towards surgeons attire in OLOL. METHODS: A
prospective survey of adult surgical in-patients was conducted from October 2013
to February 2014. A twelve-question questionnaire was used as data collection
tool, using a five point Likert scale to assess patients response to each
question. Data were collected on patient demographics, patients level of trust
and confidence based on different surgical attire, and patients perception of
different attire worn by surgical teams. RESULTS: There were 150 completed
surveys during the study period with a male to female ratio of 44% to 56%
respectively. The mean patient length of in-hospital stay (LOS) was 4.7 days
(range 1-22). The most commonly represented age group was 30-40 years (18%), with
a comparable spread among all age groups. The majority of patients found the
attire worn by surgeons on the ward to be very appropriate (93%). Majority of
responders believed scrubs to be the most appropriate attire for surgeons on
wards (39%), followed by shirt and tie with white coat (38%) followed by short
sleeved shirt and no tie (18%). Shirt and tie with white coat had a positive
effect on patients trust in 63% of responders, a negative effect in 10% and no
effect in 26%. Scrubs had a positive effect on patients trust in 63%, negative
effect in 11% and no effect in 25%. Short sleeved shirt and no tie had a positive
effect in 44%, negative effect in 25% and no effect in 30% of patients.
CONCLUSION: Patients in OLOL find attire worn by surgeons to be appropriate.
Shirt and tie with white coat or scrubs remains the patient's choice attire for
surgeons. Shirt and tie with white coat or scrubs has a more positive effect on
trust of patients compared to short sleeved shirt and no tie.
PMID- 25844383
TI - Exploring cigarette use among male migrant workers in Nigeria.
AB - BACKGROUND: There is limited knowledge about the use of cigarettes by blacks
outside the United States (U.S). Nigeria creates an opportunity to explore
smoking behaviours, smoking cessation (nicotine dependence) and use of cigarettes
in a country that has a large black population outside the U.S. METHODS: We
conducted three Focus Group Discussions (FGDs) involving twenty-four male migrant
workers who reported that they were current cigarette smokers. Interviews were
audio-taped and transcribed. RESULTS: Four major themes namely: reasons for
initiating and continuing to smoke cigarettes, factors affecting brand choice,
barriers to quitting, effect of smoking mentholated cigarette brands were
identified. CONCLUSION: This study provides insight into the use of mentholated
and non-mentholated cigarettes and suggests the need for further studies to
explore smoking behavior among Nigerians.
PMID- 25844384
TI - Knowledge and attitude toward smoke-free legislation and second-hand smoking
exposure among workers in indoor bars, beer parlors and discotheques in Osun
State of Nigeria.
AB - BACKGROUND: One of the requirements of the Osun State smoke-free legislation is
to ensure smoke-free enclosed and partially enclosed workplaces. This survey was
conducted to assess the knowledge and attitude of workers in indoor bars, beer
parlors and discotheques to smoke-free legislation in general and the Osun State
smoke-free law in particular. METHODS: A convenience sampling of 36 hospitality
centers was conducted. Interviewer-administered questionnaires were used to
elicit responses about the objectives from non-smoking workers. The
questionnaires had sections on knowledge of the Osun State smoke-free law,
attitude toward the law and smoke-free legislation in general and exposure to
second-hand tobacco smoke by the workers. Questions were also asked about the
second-hand tobacco smoking status of these workers. The data were analyzed using
SPSS version 15.0. RESULTS: We had 154 participants recruited into the study.
There were 75 males (48.0%) and 79 females (52.0%). On the overall, respondents
had a good knowledge of the effects of second-hand smoke on health (70.2%) with
75.0% of them being aware of the general smoke-free law and 67.3% being aware of
the Osun State smoke-free law although none of them had ever seen a copy of the
law. A high proportion (60.0%) was in support of the Osun smoke-free law although
all of them think that the implementation of the law could reduce patronage and
jeopardize their income. Attitude toward second-hand smoking was generally
positive with 72.0% of them having no tolerance for second-hand tobacco smoke in
their homes. Most participants (95.5%) had been exposed to tobacco smoke in the
workplace within the past week. CONCLUSION: Despite the high level of awareness
of the respondents about the dangers of second hand smoke and their positive
attitude to smoke-free laws, nearly all were constantly being exposed to second
hand smoke at work. This calls for policy level interventions to improve the
implementation of the smoke-free law.
PMID- 25844386
TI - Medical sociology as a heuristic instrument for medical tourism and cross-border
healthcare: Comment on "International patients on operation vacation -
perspectives of patients travelling to Hungary for orthopedic treatments".
AB - In this commentary, we establish a relationship between medical sociology and the
study of medical tourism and cross-border healthcare by introducing Ronald
Andersen's behavioral model of healthcare use, and linking this model to the
recent empirical study of Kovacs et al. on patients travelling to Hungary for
orthopedic treatment. Finally, we plead for more measurement in the field of
patient mobility.
PMID- 25844385
TI - Substitutes or complements? Diagnosis and treatment with non-conventional and
conventional medicine.
AB - BACKGROUND: Portugal has a strong tradition of conventional western healthcare.
So it provides a natural case study for the relationship between
Complementary/Alternative Medicine (CAM) and Western Medicine (WM). This work
aims to test the relationship between CAM and WM users in the diagnosis and
treatment stages and to estimate the determinants of CAM choice. METHODS: The
forth Portuguese National Health Survey is employed to estimate two single probit
models and obtain the correlation between the consumption of CAM and WM medicines
in the diagnosis and treatment stages. RESULTS: Firstly, both in the diagnosis
and the treatment stage, CAM and WM are seen to be complementary choices for
individuals. Secondly, self-medication also shows complementarity with the choice
of CAM treatment. Thirdly, education has a non-linear relationship with the
choice of CAM. Finally, working status, age, smoking and chronic disease are
determinant factors in the decision to use CAM. CONCLUSION: The results of this
work are relevant to health policy-makers and for insurance companies. Patients
need freedom of choice and, for the sake of safety and efficacy of treatment, WM
and CAM healthcare ought to be provided in a joint and integrated health system.
PMID- 25844387
TI - Time to shift from systems thinking-talking to systems thinking-action: Comment
on "Constraints to applying systems thinking concepts in health systems: A
regional perspective from surveying stakeholders in Eastern Mediterranean
countries".
AB - A recent International Journal of Health Policy and Management (IJHPM) article by
Fadi El-Jardali and colleagues makes an important contribution to the literature
on health system strengthening by reporting on a survey of healthcare
stakeholders in Low- and Middle-Income Countries (LMICs) about Systems Thinking
(ST). The study's main contributions are its confirmation that healthcare
stakeholders understand the importance of ST but do not know how to act on that
understanding, and the call for collective action by the global community of
systems thinkers committed to healthcare improvement. We offer three basic
considerations for next steps by this community, derived from our recent work in
ST and the related field of Knowledge Translation (KT): resist the temptation to
adopt a reductionist approach; recognize not everyone needs to understand ST; and
do not wait for everything to be in place before getting started.
PMID- 25844388
TI - Whither mental health policy-where does it come from and does it go anywhere
useful?: Comment on "Cross-national diffusion of mental health policy".
AB - Factors influencing cross-national diffusion of mental health policy are
important to understand but complex to research. This commentary discusses Shen's
research study on cross-national diffusion of mental health policy; examines the
extent to which the three questions researched by Shen (whether countries are
more likely to have a mental health policy (a) the earlier a country becomes a
member of World Health Organization (WHO), (b) the more international aid a
country receives, and (c) the more neighbouring countries already have a mental
health policy) are in fact able to assess WHO's impact on cross-national
diffusion of mental health policy. The commentary then suggests a range of more
specific questions which may be used to further elucidate the impact of WHO on an
individual country, and considers the relative value of published mental health
policy compared with the integration of mental health into national health sector
strategies and other sector reforms, and concludes with a call for more
integration of mental health across all WHO activities at international, regional
and country levels.
PMID- 25844389
TI - The changing National Health Service: market-based reform and morality: Comment
on "Morality and Markets in the NHS".
AB - This commentary explores some of the issues raised by Gilbert et al. short
communication, Morality and Markets in the NHS. The increasing role of market
mechanisms and the changing types of healthcare providers together with the use
of choice and competition to drive improvements in quality in the National Health
Service (NHS), all have important ethical implications. In order for the NHS to
continue providing the level of service quality that out performs many high
income countries, despite spending much less on healthcare, we need a re-think of
creeping marketization and privatisation and a consolidation of the NHS as a
publically owned resource run for the benefit of patients and the public, not
commercial interests.
PMID- 25844390
TI - Revealing power in truth: Comment on "Knowledge, moral claims and the exercise of
power in global health".
AB - Jeremy Shiffman's editorial appropriately calls on making all forms of power more
apparent and accountable, notably productive power derived from expertise and
claims to moral authority. This commentary argues that relationships based on
productive power can be especially difficult to reveal in global health policy
because of embedded notions about the nature of power and politics. Yet, it is
essential to recognize that global health is shot through with power
relationships, that they can take many forms, and that their explicit
acknowledgement should be part of, rather than factored out of, any reform of
global health governance.
PMID- 25844391
TI - Going beyond the hero in leadership development: the place of healthcare context,
complexity and relationships: Comment on "Leadership and leadership development
in healthcare settings - a simplistic solution to complex problems?".
AB - There remains a conviction that the torrent of publications and the financial
outlay on leadership development will create managers with the skills and
characters of perfect leaders, capable of guiding healthcare organisations
through the challenges and crises of the 21st century. The focus of much
attention continues to be the search for the (illusory) core set of heroic
qualities, abilities or competencies that will enable the development of leaders
to achieve levels of supreme leadership and organisational performance. This
brief commentary adds support to McDonald's (1) call for recognition of the
complexity of the undertaking.
PMID- 25844393
TI - Pain-Related Fear, Disability, and the Fear-Avoidance Model of Chronic Pain.
AB - Chronic pain is a significant public health concern that imposes substantial
burdens on individuals and healthcare systems, and factors that contribute to the
development and maintenance of pain-related disability are of increasing
empirical and clinical interest. Consistent with the fear-avoidance model of
chronic pain, greater pain-related fear has consistently been associated with
more severe disability and may predict the progression of disability over time.
Recent evidence indicates that treatments designed to reduce pain-related fear
are efficacious for improving disability outcomes, and several clinical trials
are currently underway to test tailored intervention content and methods of
dissemination. Future research in this area is needed to identify factors (e.g.,
substance use, comorbid psychopathology) that may influence interrelations
between pain-related fear, response to treatment, and disability.
PMID- 25844392
TI - Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-EGFR] in Dual
combination with Epirubicin-(C3-amide)-[anti-HER2/neu] against Chemotherapeutic
Resistant Mammary Adenocarcinoma (SKBr-3) and the Complementary Effect of
Mebendazole.
AB - AIMS: Delineate the feasibility of simultaneous, dual selective "targeted"
chemotherapeutic delivery and determine if this molecular strategy can promote
higher levels anti-neoplastic cytotoxicity than if only one covalent
immunochemotherapeutic is selectively "targeted" for delivery at a single
membrane associated receptor over-expressed by chemotherapeutic-resistant mammary
adenocarcinoma. METHODOLOGY: Gemcitabine and epirubicin were covalently bond to
anti-EGFR and anti-HER2/neu utilizing a rapid multi-phase synthetic organic
chemistry reaction scheme. Determination that 96% or greater gemcitabine or
epirubicin content was covalently bond to immunoglobulin fractions following size
separation by micro-scale column chromatography was established by methanol
precipitation analysis. Residual binding-avidity of gemcitabine-(C4-amide)-[anti
EG-FR] applied in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu] was
determined by cell-ELIZA utilizing chemotherapeutic-resistant mammary
adenocarcinoma (SKBr-3) populations. Lack of fragmentation or polymerization was
validated by SDS-PAGE/immunodetection/chemiluminescent autoradiography. Anti
neoplastic cytotoxic potency was determined by vitality stain analysis of
chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) monolayers known to
uniquely over-express EGFR (2 * 105/cell) and HER2/neu (1 * 106/cell) receptor
complexes. The covalent immunochemotherapeutics gemcitabine-(C4-amide)-[anti
EGFR] and epirubicin-(C3-amide)-[anti-HER2/neu] were applied simultaneously in
dual-combination to determine their capacity to collectively evoke elevated
levels of anti-neoplastic cytotoxicity. Lastly, the tubulin/microtubule inhibitor
mebendazole evaluated to determine if it's potential to complemented the anti
neoplastic cytotoxic properties of gemcitabine-(C4-amide)-[anti-EGFR] in dual
combination with epirubicin-(C3-amide)-[anti-HER2/neu]. RESULTS: Dual-combination
of gemcitabine-(C4-amide)-[anti-EGFR] with epirubicin-(C3-amide)-[anti-HER2/neu]
produced greater levels of anti-neoplastic cytotoxicity than either of the
covalent immunochemotherapeutics alone. The benzimidazole microtubule/tubulin
inhibitor, mebendazole complemented the anti-neoplastic cytotoxicity of
gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)
[anti-HER2/neu]. CONCLUSIONS: The dual-combination of gemcitabine-(C4-amide)
[anti-EGFR] with epirubicin-(C3-amide)-[anti-HER2/neu] produced higher levels of
selectively "targeted" anti-neoplastic cytotoxicity against chemotherapeutic
resistant mammary adenocarcinoma (SKBr-3) than either covalent
immunochemotherapeutic alone. The benzimidazole tubulin/microtubule inhibitor,
mebendazole also possessed anti-neoplastic cytotoxicity against chemotherapeutic
resistant mammary adenocarcinoma (SKBr-3) and complemented the potency and
efficacy of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with
epirubicin-(C3-amide)-[anti-HER2/neu].
PMID- 25844394
TI - Cost-effectiveness of community-based strategies to strengthen the continuum of
HIV care in rural South Africa: a health economic modelling analysis.
AB - BACKGROUND: Home HIV counselling and testing (HTC) achieves high coverage of
testing and linkage to care compared with existing facility-based approaches,
particularly among asymptomatic individuals. In a modelling analysis we aimed to
assess the effect on population-level health and cost-effectiveness of a
community-based package of home HTC in KwaZulu-Natal, South Africa. METHODS: We
parameterised an individual-based model with data from home HTC and linkage field
studies that achieved high coverage (91%) and linkage to antiretroviral therapy
(80%) in rural KwaZulu-Natal, South Africa. Costs were derived from a linked
microcosting study. The model simulated 10,000 individuals over 10 years and
incremental cost-effectiveness ratios were calculated for the intervention
relative to the existing status quo of facility-based testing, with costs
discounted at 3% annually. FINDINGS: The model predicted implementation of home
HTC in addition to current practice to decrease HIV-associated morbidity by 10
22% and HIV infections by 9-48% with increasing CD4 cell count thresholds for
antiretroviral therapy initiation. Incremental programme costs were US$2.7
million to $4.4 million higher in the intervention scenarios than at baseline,
and costs increased with higher CD4 cell count thresholds for antiretroviral
therapy initiation; antiretroviral therapy accounted for 48-87% of total costs.
Incremental cost-effectiveness ratios per disability-adjusted life-year averted
were $1340 at an antiretroviral therapy threshold of CD4 count lower than 200
cells per MUL, $1090 at lower than 350 cells per MUL, $1150 at lower than 500
cells per MUL, and $1360 at universal access to antiretroviral therapy.
INTERPRETATION: Community-based HTC with enhanced linkage to care can result in
increased HIV testing coverage and treatment uptake, decreasing the population
burden of HIV-associated morbidity and mortality. The incremental cost
effectiveness ratios are less than 20% of South Africa's gross domestic product
per person, and are therefore classed as very cost effective. Home HTC can be a
viable means to achieve UNAIDS' ambitious new targets for HIV treatment coverage.
FUNDING: National Institutes of Health, Bill & Melinda Gates Foundation, Wellcome
Trust.
PMID- 25844395
TI - Enteric neuron imbalance and proximal dysmotility in ganglionated intestine of
the Sox10Dom/+ Hirschsprung mouse model.
AB - BACKGROUND & AIMS: In Hirschsprung disease (HSCR), neural crest-derived
progenitors (NCPs) fail to completely colonize the intestine so that the enteric
nervous system (ENS) is absent from distal bowel. Despite removal of the
aganglionic region, many HSCR patients suffer from residual intestinal
dysmotility. To test the hypothesis that inappropriate lineage segregation of
NCPs in proximal ganglionated regions of the bowel could contribute to such
postoperative disease, we investigated neural crest (NC)-derived lineages and
motility in ganglionated, postnatal intestine of the Sox10Dom/+ HSCR mouse model.
METHODS: Cre-mediated fate-mapping was applied to evaluate relative proportions
of NC-derived cell types. Motility assays were performed to assess gastric
emptying and small intestine motility while colonic inflammation was assessed by
histopathology for Sox10Dom/+ mutants relative to wildtype controls. RESULTS:
Sox10Dom/+ mice showed regional alterations in neuron and glia proportions as
well as Calretinin+ and nNOS+ neuronal subtypes. In the colon, imbalance of
enteric NC derivatives correlated with the extent of aganglionosis. All
Sox10Dom/+ mice exhibited reduced small intestinal transit at 4-weeks of age, and
at 6-weeks, Sox10Dom/+ males had increased gastric emptying rates. Sox10Dom/+
mice surviving to 6-weeks of age had little or no colonic inflammation when
compared to wildtype littermates, suggesting that these changes in GI motility
are neurally mediated. CONCLUSIONS: The Sox10Dom mutation disrupts the balance of
NC-derived lineages and affects GI motility in the proximal, ganglionated
intestine of adult animals. This is the first report identifying alterations in
enteric neuronal classes in Sox10Dom/+ mutants, which suggests a previously
unrecognized role for Sox10 in neuronal subtype specification.
PMID- 25844396
TI - Cutaneous Melanoma in Women.
AB - The incidence of cutaneous melanoma (CM) continues to increase in the Caucasian
population in the United States. In 2014, women only accounted for 42% of the
76,100 new melanoma cases and only 33% of the 9,710 deaths associated with CM in
the US.1 These trends are consistently observed in populations around the world.
Indeed, gender disparity in melanoma outcome is so consistently observed that
gender has been suggested as an important prognostic factor in melanoma, despite
not being formerly incorporated in staging algorithms.2 The source of this gender
disparity in melanoma remains unclear but likely represents both biological and
behavioral etiologies. Herein, we review the current knowledge of how melanoma
differs between men and women.
PMID- 25844397
TI - Risk Factors for Venous Thromboembolism in Chronic Obstructive Pulmonary Disease.
AB - BACKGROUND: COPD patients are at increased risk for venous thromboembolism (VTE).
VTE however remains under-diagnosed in this population and the clinical profile
of VTE in COPD is unclear. METHODS: Global initiative for chronic Obstructive
Lung Disease (GOLD) stages II-IV participants in the COPD Genetic Epidemiology
(COPDGene) study were divided into 2 groups: VTE+, those who reported a history
of VTE by questionnaire, and VTE-, those who did not. We compared variables in
these 2 groups with either t-test or chi-squared test for continuous and
categorical variables, respectively. We performed a univariate logistic
regression for VTE, and then a multivariate logistic regression using the
significant predictors of interest in the univariate analysis to ascertain the
determinants of VTE. RESULTS: The VTE+ group was older, more likely to be
Caucasian, had a higher body mass index (BMI), smoking history, used oxygen, had
a lower 6-minute walk distance, worse quality of life scores, and more dyspnea
and respiratory exacerbations than the VTE- group. Lung function was not
different between groups. A greater percentage of the VTE+ group described
multiple medical comorbidities. On multivariate analysis, BMI, 6-minute walk
distance, pneumothorax, peripheral vascular disease, and congestive heart failure
significantly increased the odds for VTE by history. CONCLUSIONS: BMI, exercise
capacity, and medical comorbidities were significantly associated with VTE in
moderate to severe COPD. Clinicians should suspect VTE in patients who present
with dyspnea and should consider possibilities other than infection as causes of
COPD exacerbation.
PMID- 25844398
TI - FMRP regulates neurogenesis in vivo in Xenopus laevis tadpoles.
AB - Fragile X Syndrome (FXS) is the leading known monogenic form of autism and the
most common form of inherited intellectual disability. FXS results from silencing
the FMR1 gene during embryonic development, leading to loss of Fragile X Mental
Retardation Protein (FMRP), an RNA-binding protein that regulates mRNA transport,
stability, and translation. FXS is commonly thought of as a disease of synaptic
dysfunction, however, FMRP expression is lost early in embryonic development,
well before most synaptogenesis occurs. Recent studies suggest that loss of FMRP
results in aberrant neurogenesis, but neurogenic defects have been variable. We
investigated whether FMRP affects neurogenesis in Xenopus laevis tadpoles which
express a homolog of FMR1. We used in vivo time-lapse imaging of neural
progenitor cells and their neuronal progeny to evaluate the effect of acute loss
or over-expression of FMRP on neurogenesis in the developing optic tectum. We
complimented the time-lapse studies with SYTOX labeling to quantify apoptosis and
CldU labeling to measure cell proliferation. Animals with increased or decreased
levels of FMRP have significantly decreased neuronal proliferation and survival.
They also have increased neuronal differentiation, but deficient dendritic arbor
elaboration. The presence and severity of these defects was highly sensitive to
FMRP levels. These data demonstrate that FMRP plays an important role in
neurogenesis and suggest that endogenous FMRP levels are carefully regulated.
These studies show promise in using Xenopus as an experimental system to study
fundamental deficits in brain development with loss of FMRP and give new insight
into the pathophysiology of FXS.
PMID- 25844399
TI - Predicted vs. Actual Resting Energy Expenditure and Activity Coefficients: Post
Gastric Bypass, Lean and Obese Women.
AB - Total Energy Expenditure (TEE) and energy requirements are commonly estimated
from equations predicting Resting Energy Expenditure (REE) multiplied by a
Physical Activity (PA) coefficient that accounts for both PA energy expenditure
and the thermogenic effect of food. PA coefficients based on PA self-reports are
a potential source of error that has not been evaluated. Therefore, in this study
we compared: 1) the Harris-Benedict (HB), Mifflin-St. Jeor (MSJ), and the Food
and Agriculture Organization/World Health Organization/United Nations University
(FAO/WHO/UNU) REE equations with REE measured (REE-m) with indirect calorimetry;
2) PA coefficients determined with PA self-reports vs. objectively assessed PA;
and 3) TEE estimates in post-Gastric Bypass (GB = 13), lean (LE = 7), and obese
(OB = 12) women. REE was measured in the morning after an overnight fast with
participants resting supine for 30 min. Self-reported PA was evaluated with a
questionnaire and objectively measured with accelerometers worn for 5-7 days.
Nutritional intake was evaluated with a food frequency questionnaire.
Anthropometry included DEXA, and abdominal CT scans. Eligible GB had surgery >=
12 months before the study, and had >= 10 kg of body weight loss. All
participants were 18-45 years of age, able to engage in ambulatory activities,
and not taking part in exercise training programs. One-way ANOVA was used to
detect differences in REE and TEE. Accuracy of REE prediction equations were
determined by cases within 10% of REE-m, and agreement analyses. REE predictions
were not different than REE-m, but agreements were better with HB and MSJ,
particularly in the GB and LE groups. Discrepancies in the PA coefficients
determined with self-report vs. objectively assessed PA resulted in TEE
overestimates (approximately 200-300 Kcal/day) using HB and MSJ equations.
FAO/WHO/UNU overestimated TEE in all groups regardless of the PA assessment
method (approximately 300-900 kcal/day). These results suggest that: 1) HB and
MSJ equations are good predictors of REE among GB and LE, but not among OB women,
2) PA coefficients used to estimate TEE must be determined with objective PA
assessment, and 3) TEE estimates using PA coefficients with the FAO/WHO/UNU
equation must be used with caution.
PMID- 25844400
TI - IPEX Syndrome, FOXP3 and Cancer.
AB - In this review, we introduce the IPEX syndrome and its relationship with germline
mutations of the FOXP3 gene. We then describe the multiple functional roles of
FOXP3 in regulatory T cells and epithelial cells as well as in IPEX syndrome and
tumor progression. Potential mechanisms of FOXP3 inactivation and transcriptional
regulation are discussed with recent advances. Finally, we point out current
issues and a potential FOXP3-mediated therapeutic strategy as well as the
reactivation of FOXP3 in patients with IPEX syndrome and cancer.
PMID- 25844402
TI - Optimizing the Most Specific Concept Method for Efficient Instance Checking.
AB - Instance checking is considered a central tool for data retrieval from
description logic (DL) ontologies. In this paper, we propose a revised most
specific concept (MSC) method for DL SHI, which converts instance checking into
subsumption problems. This revised method can generate small concepts that are
specific-enough to answer a given query, and allow reasoning to explore only a
subset of the ABox data to achieve efficiency. Experiments show effectiveness of
our proposed method in terms of concept size reduction and the improvement in
reasoning efficiency.
PMID- 25844401
TI - SimConcept: A Hybrid Approach for Simplifying Composite Named Entities in
Biomedicine.
AB - Many text-mining studies have focused on the issue of named entity recognition
and normalization, especially in the field of biomedical natural language
processing. However, entity recognition is a complicated and difficult task in
biomedical text. One particular challenge is to identify and resolve composite
named entities, where a single span refers to more than one concept(e.g.,
BRCA1/2). Most bioconcept recognition and normalization studies have either
ignored this issue, used simple ad-hoc rules, or only handled coordination
ellipsis, which is only one of the many types of composite mentions studied in
this work. No systematic methods for simplifying composite mentions have been
previously reported, making a robust approach greatly needed. To this end, we
propose a hybrid approach by integrating a machine learning model with a pattern
identification strategy to identify the antecedent and conjuncts regions of a
concept mention, and then reassemble the composite mention using those identified
regions. Our method, which we have named SimConcept, is the first method to
systematically handle most types of composite mentions. Our method achieves high
performance in identifying and resolving composite mentions for three fundamental
biological entities: genes (89.29% in F-measure), diseases (85.52% in F-measure)
and chemicals (84.04% in F-measure). Furthermore, our results show that, using
our SimConcept method can subsequently help improve the performance of gene and
disease concept recognition and normalization.
PMID- 25844403
TI - Multi-Dimensional Scaling and MODELLER-Based Evolutionary Algorithms for Protein
Model Refinement.
AB - Protein structure prediction, i.e., computationally predicting the three
dimensional structure of a protein from its primary sequence, is one of the most
important and challenging problems in bioinformatics. Model refinement is a key
step in the prediction process, where improved structures are constructed based
on a pool of initially generated models. Since the refinement category was added
to the biennial Critical Assessment of Structure Prediction (CASP) in 2008, CASP
results show that it is a challenge for existing model refinement methods to
improve model quality consistently. This paper presents three evolutionary
algorithms for protein model refinement, in which multidimensional scaling(MDS),
the MODELLER software, and a hybrid of both are used as crossover operators,
respectively. The MDS-based method takes a purely geometrical approach and
generates a child model by combining the contact maps of multiple parents. The
MODELLER-based method takes a statistical and energy minimization approach, and
uses the remodeling module in MODELLER program to generate new models from
multiple parents. The hybrid method first generates models using the MDS-based
method and then run them through the MODELLER-based method, aiming at combining
the strength of both. Promising results have been obtained in experiments using
CASP datasets. The MDS-based method improved the best of a pool of predicted
models in terms of the global distance test score (GDT-TS) in 9 out of 16test
targets.
PMID- 25844404
TI - INSIGHTS INTO THE MECHANICS OF CYTOKINETIC RING ASSEMBLY USING 3D MODELING.
AB - During fission yeast cytokinesis, actin filaments nucleated by cortical formin
Cdc12 are captured by myosin motors bound to a band of cortical nodes. The myosin
motors exert forces that pull nodes together into a contractile ring. Cross
linking interactions help align actin filaments and nodes into a single bundle.
Mutations in the myosin motor domain and changes in the concentration of cross
linkers alpha-actinin and fimbrin alter the morphology of the condensing network,
leading to clumps, rings or extended meshworks. How the contractile tension
developing during ring formation depends on the interplay between network
morphology, myosin motor activity, cross-linking and actin filament turnover
remains to be elucidated. We addressed this question using a 3D computational
model in which semiflexible actin filaments (represented as beads connected by
springs) grow from formins, can be captured by myosin in neighboring nodes, and
get cross-linked with one another through an attractive interaction. We identify
regimes of tension generation between connected nodes under a wide set of
conditions regarding myosin dynamics and strength of cross-linking between actin
filaments. We find conditions that maximize circumferential tension, correlate
them with network morphology and propose experiments to test these predictions.
This work addresses "Morphogenesis of soft and living matter" using computational
modeling to simulate cytokinetic ring assembly from the key molecular mechanisms
of viscoelastic cross-linked actin networks that include active molecular motors.
PMID- 25844405
TI - [From the editor - epidemiology of mental diseases].
PMID- 25844406
TI - ["Epidemiology of mental disorders and access to mental health care. EZOP -
Poland" - research methodology].
AB - AIM: Since the second half of the twentieth century, with the development of
structured diagnostic tools, population based studies on epidemiology of mental
disorders are carried out. A special role is played by World Mental Health Survey
Initiative which brings together a group of countries from different continents
in order to carry out research projects according to standard methodology using
the Composite International Diagnostic Interview. Polish EZOP study, which was
conducted in accordance with the guidelines of WMH joined that group. The project
was implemented under the Norwegian Financial Mechanism and the Financial
Mechanism of the European Economic Area. Its aim was to estimate the prevalence
of mental disorders in the Polish population of adults, assess the distance to
mental disorders and to obtain knowledge about the perception of psychiatric
disorders and treatment. METHODS: The research tool was the Polish version of
CIDI-WHO ver.3.0., which was developed for the project. The study was performed
in accordance with the guidelines of WMH (cognitive interviews, interviewers
training, standardization of field procedures) using electronic version of CIDI
questionnaire (CAPI) within the 2-stages procedure in randomly selected
representative sample of the Polish population aged 18-64. The quality of the
study was systematically controlled and reported by MB SMG/KRC, and completed
data (10,081 interviews) were sent to the Department-Centre of Monitoring and
Analyses of Population Health NIPH-NIH. After the initial analysis data were sent
to the analytical center of WMH, which applied additional cleaning tools and
added new variables representing psychiatric diagnoses in DSM-IV and ICD-10.
PMID- 25844407
TI - [The prevalence of common mental disorders in the population of adult Poles by
sex and age structure - an EZOP Poland study].
AB - AIM: The article presents lifetime (LT) prevalence of common mental disorders
(CMD) in accordance with the DSMIV classification, based on assessment of
representative population sample of 10,081 Poles aged 18-64. METHODS: Computer
based WHO CIDI3.0 was adapted for the Polish population according to WMH
protocol. The survey was performed by certified and supervised interviewers.
RESULTS: Out of the 18 CMDs analyzed the most common was alcohol abuse,
significantly more often in males (18.6%) than in women (3.3%), (p<0.01). The
second most common disorder was panic, also more frequent in women (8.5%) than in
men (3.9%), (p<0.01). Similarly, depression occurred in women (4.0%) two times
more often than in males (1.9%), (p<0.01). GAD, agoraphobia, panic, specific
phobia (p<0.01), and dysthymia (p<0.05) were also more prevalent in women. On the
other hand, alcohol abuse, alcohol and drug dependence (p<0.01), and hypomania
(p<0.05) were more common in males. For most analyzed disorders significantly
higher prevalence was found in the older age groups. Social phobia, specific
phobias, and drug abuse occurred most often in men from the youngest group. No
significant differences related to age were found for the prevalence of hypomania
both in men and women. CONCLUSIONS: Indices of prevalence obtained in the EZOP
Poland study differ from the indices of prevalence of mental disorders described
earlier in other countries. Lower values were found in Poland for affective
disorders and some anxiety disorders. Only alcohol abuse was diagnosed more often
than in other studies using similar methods except Ukraine, where this disorder
was diagnosed with similar frequency.
PMID- 25844408
TI - [Effectiveness of intensive group psychotherapy in treatment of neurotic and
personality disorders].
AB - AIM: The aim of this study was to analyze the effectiveness of intensive (150 -
210 sessions), short-term (10 - 14 weeks) group psychotherapy in the treatment of
neurotic disorders, and selected personality disorders. METHODS: The study
involved 145 patients treated in day hospital due to neurotic disorders and
selected personality disorders. The measurements were performed twice - at the
beginning and at the end of hospitalization. The effectiveness of psychotherapy
in the reduction of symptoms of neurotic disorders was measured with symptom
checklist "0". The change in the severity of personality traits characteristic
for neurotic disorders was examined using Neurotic Personality Questionnaire KON
2006. RESULTS: A significant reduction in symptoms of neurotic disorders was
found in 84% of patients (85,7% women and 80,8% men). 70,3% of the examined
patients obtained in the measurement at the end of treatment results indicating
the level of severity of neurotic disorders symptoms below the cutoff point
separating population of healthy individuals from patients. A significant
reduction in the severity of personality traits characteristically occurring in
patients suffering from neurotic disorders was found in 76% of patients (74.5%
women and 78.7% men). 42.8% of the examined patients obtained in the measurement
at the end of the treatment the value of neurotic personality traits index (X
KON) typical for healthy population. CONCLUSIONS: Intensive, short-term group
psychotherapy with elements of individual therapy is an effective treatment for
neurotic disorders. The majority of treated persons obtains a significant
symptomatic improvement and a reduction in the severity of neurotic personality
traits.
PMID- 25844409
TI - [Psychotherapy for pregnant women with psychiatric disorders].
AB - Pregnancy is a major life change for many women. The related biological changes,
especially complications in its course and in the course of delivery, carry a
risk of developing a variety of psychological problems and mental disorders.
However, their treatment is challenging due to the teratogenic effects of most
psychoactive drugs and specific requirements for entering different
psychotherapeutic programs. Mental disorders during pregnancy are undoubtedly an
important issue for both gynecology and psychiatry. There is still a discussion
considering the question whether psychotherapy during pregnancy is safe, although
no scientifically valid data contradicting the safety of psychotherapy during
pregnancy has been published so far. Together with psychotherapy - as a treatment
of choice - clinicians approve some other relatively safe treatment methods for
psychiatric disorders in pregnant women. Light therapy, limited pharmacotherapy,
ECT are included. The goal of this paper is to review current opinions of
clinicians and researches concerning possibilities, indications and outcome of
psychological treatments as a way to help pregnant women who suffer from
different psychiatric conditions, and also because this subject is not yet
present in Polish psychiatric journals.
PMID- 25844410
TI - [Attentional bias training in reducing symptoms of anxiety].
AB - Anxiety is related to attentional bias, i.e. a tendency to pay attention to
threatening stimuli. This occurs both in individuals suffering from anxiety
disorders, and in healthy individuals with elevated levels of trait anxiety. This
article is an analysis of a research paradigm, used to modify attentional bias
(CBM-A Cognitive Bias Modification - Attention). A growing number of studies
indicate that with the help of computer methods such as a modified version of the
dot-probe task we can train individuals to direct attention away from threatening
stimuli, which in turn reduces symptoms of anxiety. This effect was observed in
adults, adolescents and children suffering from social phobia, generalised
anxiety disorder and subclinical symptoms of obsessive-compulsive disorder.
Effectiveness of this method constitutes the evidence for attentional bias being
among the causes of anxiety disorders. The article also analyses the still not
completely clear mechanisms of CBM-A and limitations of this method.
PMID- 25844411
TI - [The place of quetiapine extended release in the treatment of mental disorders].
AB - This article presents a summary of available data on the use of quetiapine
extended release (QUE-XR). QUE-XR is an example of an atypical antipsychotic drug
that can be used in a single dose, thereby simplifying the treatment regimen.
From the therapeutic standpoint, this issue is of paramount importance, since
approximately 50% of patients have adherence issues. Therefore, availability of
the drug which is comfortable in administration can significantly improve
treatment outcomes. Due to its antipsychotic, antidepressive, mood stabilizing
and anxiolytic efficacy, QUE-XR seems to be a promising drug with potentially
broad spectrum of indications (in patients with schizophrenia, bipolar disorder,
major depression and some anxiety disorders - both in the acute phase of
treatment, and the maintenance treatment). Notably, QUE-XR seems to ameliorate
sleep disturbances, and it may also improve patients' quality of life (as
suggested by some studies). Due to the simple dosing regimen of QUE-XR,
conducting therapy with this drug may contribute to the improvement of
compliance. Yet, the primary clinical criterion for selection of the type of
formulation of quetiapine should be the individual preferences of the patient,
and the knowledge and experience of the treating physician.
PMID- 25844412
TI - [Misuse and abuse of quetiapine].
AB - Quetiapine is an atypical antipsychotic agent, frequently used in psychiatry,
often for symptomatic treatment against a number of mental disorders differing
from the registration indications. One of the use is to soothe the clinical
conditions caused by the use of various psychoactive substances. The paper
presents and discusses the reports of quetiapine misuse, abuse, and even mental
addiction, as well as symptoms similar to the so-called discontinuation syndrome,
often mixed with withdrawal syndrome occurring in the course of addiction. Most
reports concern males, and especially those with a history of other psychoactive
substance abuse, and personality disorders, often in conflict with the law.
Therefore, clinicians should be cautious when prescribing quetiapine to such
patients. The article discusses potential mechanisms responsible for quetiapine
abuse. This is probably related to its sedative and anxiolytic activity which
results in the frequent use with stimulants. Also, high affinity for the H1
receptor, as antihistamines agents causes rewarding action.
PMID- 25844413
TI - [The Polish adaptation of the public speaking anxiety questionnaire].
AB - OBJECTIVES: The aim of the study was the Polish adaptation of the shortened
Public Speaking Anxiety Questionnaire GFER by Spitznagel and co-workers. METHODS:
GFER is a self-assessment method which consists of 16 statements and is designed
to assess emotions, physiological reactions, and thoughts that appear in a
situation of public speaking. GFER was used to examine 320 students from Lodz's
universities. The State/Trait Anxiety Inventory - STAI by Spielberger, The
Hospital Anxiety and Depression Scale by Zigmunt and Snaith and TCI by Cloninger
were also used. RESULTS: The Polish version of GFER is a reliable and valid tool.
The factor structure is similar to the original structure. As a result of the
conducted analyses, there was obtained the 9-item version of the tool, which has
a 2-factor structure - factor I: emotional and physiological reactions, factor
II: worrying. The results obtained with GFER present a statistically significant
correlation with other measures of anxiety and with the dimension of temperament:
harm avoidance. CONCLUSIONS: The obtained results indicate that GFER may be used
in both scientific research and therapeutic practice.
PMID- 25844414
TI - [Perceived Autonomy in Old Age scale: Factor structure and psychometric
properties of the Polish adaptation].
AB - AIM: Sense of autonomy - the possibility to choose and decide - is one of the
markers of positive and active aging. The goal of this study was to examine the
Polish adaptation of the Perceived Autonomy in Old Age (PAA) scale and to
determine its internal structure and psychometric properties: reliability, as
well as construct and discriminant validity. METHODS: 277 seniors (female=187;
male=90), without cognitive function disorders aged 60 to 100 (M=77.4; SD=9.2)
took part in the study. Apart from the PAA, the ADL and IADL scales (self
reliance assessment) were used, as well as the Emotional State Questionnaire (a
measure for positive and negative emotions) and the WHOQoL-Brief (a measure for
health-related quality of life). RESULTS: As a result of an exploratory and
confirmation factor analysis a one-factor tool with five items was built.
Reliability coefficients of the scale measured with the internal consistency
method and test-retest were >= 0.80. Positive correlations were found with
indicators in the ADL, IADL, as well as in the somatic and psychological domain
of life quality, and positive emotions. Negative correlations were found for
negative emotions. CONCLUSIONS: The obtained results indicated very high
reliability and accuracy for the Polish adaptation of the SPA. The tool can be
used as a predictor and/or indicator of successful aging and life quality of
seniors.
PMID- 25844415
TI - [Validation of ORTO-15 Questionnaire in the group of urban youth aged 15-21].
AB - AIM: The aim of the study was the validation and adaptation of the ORTO-15
Questionnaire in the group of the Polish schoolgirls and schoolboys. METHODS: The
study included 399 participants (15-21 years old), all of them high school
students in the city of Sosnowiec. The ORTO-15 is a tool created in Italy by L.M.
Donini, comprising of 15 items describing intensification of orthorexia risk
(population diagnosis). The validation procedure incorporated three basic methods
to be applied in the reliability analysis - the comparison of double tests with
the same method, the statistical properties analysis of test items as well as
analysis of the relation of test items with the general test result. Moreover,
the compliance of the ORTO-15 Questionnaire results with other questionnaire
focused on eating habits (EAT-26) was studied. RESULTS: The reliability analysis
of the ORTO-15 Questionnaire based on repeatability of the responses presents a
very good (kappa: 0.81 - 1.00 for 5 items) and a good repeatability (kappa: 0.61
0.80 for 10 items). The reliability analysis based on the value of the
Cronbach's alpha reached a satisfactory level (0.7 - 0.9). A full agreement of in
the occurrence of orthorexia risk and the risk of eating disorders concerned
47.2% (Kappa = 0.04; 95% CI: 0.004 - 0.09) for the Ortho-40 and 88.2% (Kappa =
0.32; 95% CI: 0.17 - 0.47) for the Ortho-35. CONCLUSIONS: The ORTO-15
questionnaire is a reliable tool to identify the risk of ON in population studies
in the group of urban youth aged 15 - 21.
PMID- 25844416
TI - [Psychometric properties of the Polish version of the brief version of Kutcher
Adolescent Depression Scale - assessment of depression among students].
AB - AIM: Depressive disorders, which remain one of the most common and recurrent mood
disorders worldwide, presently affect up to 15% of the population under age 25.
Adolescent depression is related to a number of adverse phenomena such as
scholastic/academic failure, juvenile delinquency, illicit substance abuse or
suicide. Studies show that students are at a high risk of developing this
disorder but depression in this population is often misdiagnosed and
undertreated. Consequently, it is important to develop reliable diagnostic tools
to evaluate symptoms of depression in students. Kutcher Adolescent Depression
Scale (brief version) is a commonly used screening test used to identify young
people at risk for depression, which consists of six items related to its main
symptoms. The aim of the study was to adapt and test reliability and content
validity of the Polish version of six - item Kutcher's KADS based on analysis of
students using confirmatory factor analysis. MATERIAL AND METHODS: A total of
1,589 student aged 18-24 anonymously answered a questionnaire on the risk of
depression (KADS) and a demographics survey. RESULTS: Confirmatory factor
analysis showed the good fit of model to empirical data: SB chi2 (15) = 968.688,
p < .001, RMSEA = .053, CFI = .958, SRMR = .029. Factor loading ranged from .40
to .80. CONCLUSIONS: Validation of Polish version of KADS in a group of students
aged 18-24 years has shown its high reliability and content validity. Further
studies should be focused on the assessment of the questionnaire criterion
validity.
PMID- 25844417
TI - [The study of the Polish version of the Questionnaire for the Assessment of
Disgust Sensitivity (QADS)].
AB - AIM: Disgust is one of the principal emotions, typically triggered by a variety
of biological and social stimuli. Several questionnaire tools have been used to
assess disgust. The aim of the study was to assess psychometric properties of the
Polish version of the Questionnaire for the Assessment of Disgust Sensitivity
(QADS), adapted from the tool prepared by the German researchers. METHODS: Eight
hundred twenty subjects (631, 77% females and 189, 23% males) aged 18-69 (mean -
28 years) participated in the study. There are 3 subscale in the questionnaire:
Core Disgust, Animal Reminder and Contamination. The tool consists of 37 items,
the intensity of feeling of disgust is assessed based on 5-point Likert scale.
RESULTS: Confirmatory factor analysis confirmed the adequacy of grouping of items
in the three subscales: Core Disgust, Animal-Reminder, and Contamination
Interpersonal. In our sample, females had higher levels of disgust than males.
Several other psychometric variables - high degree of correlations between the
subscales, and high reliability -were in agreement with parameters of the
original version. The Polish version compared favourably with the original, with
Cronbach's alpha of 0.94 for the whole questionnaire and 0.85 - 0.90 for the
subscales. CONCLUSIONS: The psychometric properties of the Polish version of QADS
are sufficient to recommend this tool for diagnostic and research use.
PMID- 25844418
TI - [Diagnosis of Posttraumatic Stress Disorder (PTSD) by the Structured Clinical
Interview SCID-I].
AB - OBJECTIVES: Valid and reliable diagnosis of posttraumatic stress disorder is
important for clinical practice, scientific research and forensic settings. The
aim of the study was to assess the psychometric properties of the Polish version
of SCID-I F Module for the diagnosis of PTSD. METHODS: Five hundred twenty six
motor vehicle accident survivors participated in the study. Clinical diagnosis
was based on SCID-I-PTSD interview. Participants filled out a set of self-report
inventories concerning PTSD symptoms (PDS), depression (BDI-II), anxiety (STAI)
and posttraumatic cognitions (PTCI). RESULTS: The interview assessment showed
high reliability and both convergent and discriminative validity. SCID-I-PTSD
interview proved to be more specific than PDS inventory. Interview items show
good psychometric properties (except an item C3) and no differential item
functioning for sex. Latent structure analysis of PTSD symptoms were
nonconclusive. CONCLUSIONS: A part of Module F of the SCID-I, a structured
clinical interview for the assessment of posttraumatic stress disorder is a valid
and reliable psychometric tool useful for the diagnosis of PTSD.
PMID- 25844420
TI - [The diagnostic usability of selected narrativity indices in stories about close
relationships in the assessment of personality organization].
AB - AIM: The aim of this study was to test the usability of selected narrativity
indices identified from autobiographical accounts of important relationships in
an assessment of neurotic (NPO) and borderline personality organization (BPO).
METHODS: Narrativity indices, both particular and generalized, were used to
predict personality organization levels. Indices were derived from two separate
layers of analysis: 1) lexical indices were counted with computer assistance; 2)
evocative/reception indices dealing with coherence of the story were assessed
using the competent judges method. RESULTS: It was found that the lexical
narrativity index-the active "I"-was a good predictor of both BPO and NPO, while
the human factor was a good predictor of BPO when low. Moreover, a generalized
index was used to describe how stories are saturated with the narrativity indices
of intentionality, concreteness, and active "I", but simultaneously deprived of
human factor, and was found to be the best predictor of BPO. Furthermore, where
the coherence of the story and of its subdimension (integration) rise, the
probability of BPO diagnosis decreases. CONCLUSIONS: This research provides
support for the thesis that surface narrativity indices may predict deeper
personality structure. Its results are justified in the light of Kernberg's
theory, and have the potential to become a useful tool in clinical practice as a
supplementary source of information in diagnostic and psychotherapeutic
processes.
PMID- 25844421
TI - Assessing humanity's global impact.
PMID- 25844419
TI - [The Montreal Cognitive Assessment 7.2--Polish adaptation and research on
equivalency].
AB - AIM: The Montreal Cognitive Assessment is a screening test for diagnosis of Mild
Cognitive Impairment- MCI. Only one version of the method was available in Poland
so far. In order to assess progression of cognitive impairment, or to diagnose
effectiveness of therapy, two equivalent version of method are needed. English
additional version 7.2. was translated and culturally adapted to sustain
reliability of the assessment. Then equivalency of both Polish versions was
investigated. This paper examines whether both Polish versions of MoCA are
equivalent, and describes the process of its cultural adaptation. METHODS: 66
psychiatric patients (37 men, 29 women) with different levels of cognitive
impairment were examined using both Polish versions of MoCA. Both versions were
administered randomly to patients with no time interval in between. RESULTS: No
significant differences (p=0,601) for total MoCA scores were found between first
version of Polish MoCA, and alternate version. Equivalency measured by
correlation coefficient Spearman's rho correlation coefficient (rho=0,926) proved
to be high. CONCLUSIONS: Both Polish versions of MoCA are equivalent, and can be
useful in repeated measurement of progress in cognitive impairment or in testing
of the effectiveness of treatment.
PMID- 25844422
TI - Q&A: Stephen M. Kosslyn.
PMID- 25844423
TI - Home healthcare: expertise needed.
PMID- 25844424
TI - [A loud reflection...].
PMID- 25844425
TI - [Farewell].
PMID- 25844426
TI - The introduction of a lightweight mini vaporizer and malignant hyperthermia:
author reply.
PMID- 25844427
TI - [Jaime Celestino da Costa].
PMID- 25844428
TI - Occupational health: additional support for the aging anesthesiologist: author
reply.
PMID- 25844429
TI - Associations of breaks in sedentary time with abdominal obesity in Portuguese
older adults.
AB - In older adults, sedentary time is positively associated with obesity. The manner
in which it is accumulated, i.e., the number of breaks in sedentary time, might
be also important. We examined the cross-sectional associations of breaks in
sedentary time with abdominal obesity in 301 older adults (111 men and 190 women)
aged 75.0 +/- 6.8 years. Sedentary time (counts min(-1) < 100) and physical
activity were objectively measured by accelerometry, worn during waking hours for
at least three consecutive days. A break was defined as an interruption (>= 100
counts min(-1) < 2020) in sedentary time while performing light intensity
physical activities. Sedentary time was expressed as the number of daily breaks
in sedentary time or hourly breaks in sedentary time. Abdominal obesity was
defined by waist circumference (men >102 cm; women >88 cm). Using binary logistic
regression analyses, the odds for abdominal obesity decreased 7 % for each
additional hourly break in sedentary time in women (OR = 0.93, 95 % CI: 0.87
1.00), but not men, independently of total sedentary time and moderate-to
vigorous physical activity. The odds for abdominal obesity were 3.21 times higher
(p = 0.039) for women in quartile 1 (<225 breaks day(-1)) of daily breaks in
sedentary time compared to those in quartile 4 (>353 breaks day(-1)) of daily
breaks in sedentary time.These findings indicate that older women who interrupt
their sedentary time more frequently are less likely to present abdominal
obesity. Public health recommendations regarding breaking-up sedentary time
complementary to those for physical activity are likely to be relevant.
PMID- 25844430
TI - Plant salt tolerance: adaptations in halophytes.
AB - BACKGROUND: Most of the water on Earth is seawater, each kilogram of which
contains about 35 g of salts, and yet most plants cannot grow in this solution;
less than 0.2% of species can develop and reproduce with repeated exposure to
seawater. These 'extremophiles' are called halophytes. SCOPE: Improved knowledge
of halophytes is of importance to understanding our natural world and to enable
the use of some of these fascinating plants in land re-vegetation, as forages for
livestock, and to develop salt-tolerant crops. In this Preface to a Special Issue
on halophytes and saline adaptations, the evolution of salt tolerance in
halophytes, their life-history traits and progress in understanding the
molecular, biochemical and physiological mechanisms contributing to salt
tolerance are summarized. In particular, cellular processes that underpin the
ability of halophytes to tolerate high tissue concentrations of Na+ and Cl-,
including regulation of membrane transport, their ability to synthesize
compatible solutes and to deal with reactive oxygen species, are highlighted.
Interacting stress factors in addition to salinity, such as heavy metals and
flooding, are also topics gaining increased attention in the search to understand
the biology of halophytes. CONCLUSIONS: Halophytes will play increasingly
important roles as models for understanding plant salt tolerance, as genetic
resources contributing towards the goal of improvement of salt tolerance in some
crops, for re-vegetation of saline lands, and as 'niche crops' in their own right
for landscapes with saline soils.
PMID- 25844431
TI - In the midst of a large measles outbreak, EDs take steps to bolster screening
procedures, prevent potential transmissions.
AB - A large, multi-state outbreak of measles is prompting EDs around the country to
bolster their screening procedures and provide education to staff, most of whom
have never seen a measles case. Dozens of people in more than 17 states have been
confirmed to have the disease, with most of these cases associated with an
outbreak that began at an amusement park in southern California. Measles is
extremely contagious, infecting nine out of 10 people exposed to the virus if
they are susceptible to the disease. In cases in which a contagious disease is
suspected, experts advise emergency providers to protect themselves before
proceeding to the traditional vital signs. It's a concept referred to as "vital
sign zero." Once a measles case is confirmed, experts say emergency staff should
isolate the patient with protection such as an N-95 mask, and inform both the
hospital's infection control department and public health authorities.
PMID- 25844432
TI - The role of emergency medicine in curbing, preventing measles outbreaks.
PMID- 25844433
TI - New type of center focuses on caring for the most critically ill patients,
decompressing ED that serves patients at the upper end of the acuity spectrum.
AB - The University of Michigan Health System (UMHS) in Ann Arbor has opened a new
unit within its ED to focus on caring for the most critically ill patients Who
present to the ED. Dubbed the Massey Emergency Critical Care Center, or EC3, the
model is the first of its kind in the country, with its own ICU and a lower nurse
patient ratio than the main ED to facilitate closer monitoring. Developers
hope.the new unit will decompress the ED, shorten wait times, and potentially
reduce the demand for ICU care on the upper floors. The adult ED at UMHS receives
patients on the higher end of the acuity spectrum, with high-acuity patients
making up 90% of the patient volume. Staffing of the EC3 includes emergency
nurses and physicians who have had extra training in critical care. The EC3 will
serve as a new research center for emergency critical care patients, and a
training ground for physicians and nurses looking to enhance their skills in
critical care.
PMID- 25844434
TI - Study: bacterium associated with rare "forgotten" disease also responsible for
more sore throats than Group A strep in young adults.
AB - New findings show that Fusobacterium necrophorum, the bacterium responsible for
most cases of Lemierre's disease, a relatively rare condition that is sometimes
called "the forgotten disease," is also the culprit for more sore throats than
Group A strep bacterium among college-aged patients. However, as there is no
point-of-care test for F. necrophorum, providers need to rely on physical
examination when determining whether a sore throat is due to the bacterial
infection. In an analysis of 312 college students, investigators detected F.
necrophorum in more than 20% of patients with symptoms of sore throat. Group A
strep was only detected in 10% of the cases, and Group C or G strep was detected
in 9% of the cases. Researchers note that the F. necrophorum bacterium is
associated with both Lemierre's disease and most cases involving a peritonsillar
abscess, a deep infection of the head or neck that occurs most commonly in young
adults. Infections caused by F. necrophorum can be effectively treated with
penicillin or a cephalosporin, but do not typically respond to azithromycin.
PMID- 25844435
TI - [Macular surgery in a new point of view].
AB - PURPOSE: To reveal the differences in anatomical and functional results following
standard 20-gauge vitrectomy and modern transconjunctival sutureless vitrectomy
in macular surface pathology. MATERIALS AND METHODS: Retrospective,
interventional, comparative evaluation of macular pathology cases operated by
standard 20-gauge vitrectomy and transconjunctival 23 G sutureless vitrectomy. In
evaluation were included a comparable number of epiretinal membranes (both
idiopathic and secondary) and stage 3 and 4 macular holes. A postoperative
anatomical and functional analysis was performed and also the incidence of pre
and postoperative complications was noted. RESULTS: Transconjunctival sutureless
vitrectomy was associated with a shorter operating time and quicker anatomical
and functional results. If in epiretinal membranes there was no significant
difference in final results, in macular holes anatomical and functional results
were better with sutureless vitrectomy. CONCLUSIONS: These results confirm the
efficacy and safety of both surgical procedures in macular surface pathology.
Better anatomical and functional results in macular holes and quicker functional
rehabilitation in all cases promote sutureless vitrectomy as new standard
procedure in these cases.
PMID- 25844436
TI - [Thermophilic prokaryotes from deep subterranean habitats].
AB - The deep continental biosphere consists of geologically isolated ecosystems
differing in their physicochemical, geological, and trophic parameters. Most of
the deep ecosystems exist at elevated temperatures (50-120 degrees C), which
favor the development of thermophilic microorganisms. In many cases, indigenous
nature of subsurface microorganisms is questionable due to problems of collecting
representative and non-contaminated samples. In spite of the numerous studies on
the deep biosphere microbial communities, the number of cultivated thermophiles
isolated from subsurface environments not associated with petroleum deposits does
not exceed 30 species. More than half of the thermophilic species isolated from
deep subsurface belong to the Firmicutes. Majority of the underground
thermophiles are subsurface strict or facultative anaerobes, with capacity for
sulfate and iron reduction are notably widespread. Most thermophilic subsurface
microorganisms are organotrophs, although chemolithoautotrophic thermophiles also
have been reported. This review deals with the phylogenetic diversity and
physiological properties of the cultivated thermophilic prokaryotes isolated from
various deep subterranean habitats.
PMID- 25844437
TI - [Trehalose: chemical structure, biological functions, and practical application].
AB - Up-to-date information concerning the chemical structure and properties of
trehalose, its natural occurrence and biological functions in plants, fungi, and
prokaryotes, as well as its practical application, mainly in medicine and
biotechnology, are reviewed. A special section deals with the role of trehalose
and other protective polyols in stress processes in fungi.
PMID- 25844438
TI - [Changes in the phase variant spectra in the populations of lactic acid bacteria
under antibiotic treatment].
AB - Effect of the antibiotics kanamycin and ampicillin on growth and phase variation
of the populations of four strains of lactic acid bacteria (Lactobacillus sp.
M67AT, L. casei MB, Enterococcus faecium M, and E. faecium M3185) was studied.
The presence of antibiotics in the medium resulted in a dose-dependent decrease
in viable cell numbers and in partial or complete substitution of the dominant S
variant with the minor Sm and Sb variants. The variants differed in colony
morphology, as well as in some physiological, biochemical, biotechnological, and
probiotic characteristics. The Sm type variants of all strains exhibited the
highest resistance to antibiotics. High production of exopolysaccharides was
found in Sb variants of lactobacilli and in S variants of enterococci. The
highest antibacterial activity was found in Sm variants of lactobacilli,
especially in Lactobacillus sp. M76AT The latter is biotechnologically the most
promising strain, since all variants fermented milk yielding the products with
uniformly pronounced functional and organoleptic properties. These patterns are
of importance for the understanding of the mechanisms of antibiotic resistance
and for selection of the variants with desired properties, as well as for quality
control of the lactic acid bacteria starter cultures.
PMID- 25844439
TI - [Functional activity of the modA, gene in Methylobacterium dichloromethanicum
DM4].
AB - The putative METDI2644 (modA2) gene of Methylobacterium dichloromethanicum DM4,
present in the 126-kbp chromosomal fragment associated with dichloromethane (DCM)
degradation was investigated. While this gene is presumed to encode the
periplasmic substrate-binding subunit of the molybdate ABC transporter, its
conceptual translation also exhibits similarity to the proteins containing the
ostA conservative domain and responsible for resistance of gram-negative bacteria
to organic solvents. Reverse transcription polymerase chain reaction (RT-PCR)
revealed the RNA transcripts of this gene in the cells grown on either DCM or
methanol. The mobilizable suicide vector pK18mob was used to obtain a knockout
mutant with the METDI2644 gene inactivated by insertion of the gentamycin
cassette. The mutant pregrown on methanol exhibited lower growth rate on DCM than
the wild-type strain DM4. The difference was not alleviated by addition of sodium
molybdate. Our results suggest that the METDI2644 gene product plays a role in
cell adaptation to DCM degradation.
PMID- 25844440
TI - [Periplasmic lysozime inhibitior PliC and its role in antilysozime activity of
enterobacteria].
AB - Two families of specific inhibitors of type C lysozyme (Ivy and PliC) secreted
from the periplasmic space are known in enterobacteria. Microbial capacity for
distant lysozyme inactivation (antilysozyme activity) is most pronounced in the
strains and species carrying homologues of the pliCgene. The pliC homologue
localized in a -200-kbp megaplasmid of Klebsiella pneumoniae was shown to differ
significantly in the amino acid composition of the coded polypeptide. Similar to
the Salmonella enterica pliC homologue, it possesses a detachable signal part and
contains identical functionally critical amino acids of the active center of the
inhibitor. Antilysozyme activity of the pliC-positive K. pneumoniae strains was
observed at the level corresponding to the highest values found inpliC-positive
S. enterica. High level of the antilysozyme activity in K. pneumoniae strains
containing the plasmid pliC homologue was found in all studied strains, unlike S.
enterica strains carrying the known chromosomal pliC homologue.
PMID- 25844442
TI - [Ribonucleolytic activity of mycoplasmas].
AB - Mycoplasmas are incapable of de novo synthesis of nucleotides and must therefore
secrete nucleases in order to replenish the pool of nucleic acid precursors. The
nucleolytic activity of mycoplasmas is an important factor in their
pathogenicity. Bacterial ribonucleases (RNases) may produce a broad spectrum of
biological effects, including antiviral and antitumor activity. Mycoplasma RNases
are therefore of interest. In the present work, capacity of Acholeplasma
laidlawii and Mycoplasma hominis for RNase synthesis and secretion was studied.
During the stationary growth phase, these organisms were found to synthesize
Mg(2+)-dependent RNases, with their highest activity detected outside the cells.
Localization of A. laidlawii RNases was determined: almost 90% of the RNase
activity was found to be associated with the membrane vesicles. Bioinformational
analysis revealed homology between the nucleotide sequences of 14 Bacillus
subtilis genes encoding the products with RNase activity and the genes of the
mycoplasmas under study. Amino acid sequences of 4 A. laidlawii proteins with
ribonuclease activity and the Bsn RNase was also established.
PMID- 25844441
TI - [Characterization, identification, and screening for tetrodotoxin production by
bacteria associated with the Cephalotrix simula (Ivata, 1952) proboscis worm].
AB - The taxonomic composition of bacteria associated with the Cephalotrix simula
proboscis worm was studied and screening of the tetrodotoxin (TTX)-producing
bacteria was carried out using confocal laser scanning microscopy and polyclonal
antibodies. Bacterial isolates were identified using the 16S rRNA gene sequencing
and phenotypic characteristics. A Bacillus species was found to be responsible
for tetrodotoxin production in C. simula proboscis worms. Vibrio spp.
predominated in the associated microflora (68.18% of the total number of
isolates). Analysis of the sensitivity of 16 strains to antibiotics of various
classes revealed multiple resistance to three or more antibiotics in all studied
isolates. Poor growth of most of the isolates on all laboratory media was an
indirect confirmation of the symbiotic relationships between the micro- and
macroorganisms.
PMID- 25844444
TI - [Comparative assessment of inductive effects of Azospirillum lectins with
different antigenic properties on the signal systems of wheat seedling roots].
AB - The lectins of associative nitrogen-fixing bacteria Azospirillum brasilense Sp7
and its mutant A. brasilense Sp7.2.3 were shown to have different effects on the
components of the wheat seedling root signal system, namely to regulate the
levels of cAMP, nitric oxide, diacylglycerol, and salicylic acid, as well as to
induce the activities of superoxide dismutase and lipoxygenase. Our results make
it possible to consider azospirilla lectins as inducers of the signal systems in
wheat seedling roots, since they cause development of several flows of primary
signals. These data are of general biological importance, since lectins are
present in all living organisms and most ot the functions of lectins remain
insufficiently understood.
PMID- 25844443
TI - [Effect of temperature on the rate of oxidation of pyrrhotite-rich sulfide ore
flotation concentrate and the structure of the acidophilic chemolithoautotrophic
microbial community].
AB - Oxidation of flotation concentrate of a pyrrhotite-rich sulfide ore by
acidophilic chemolithoautotrophic microbial communities at 35, 40, and 45 degrees
C was investigated. According to the physicochemical parameters of the liquid
phase of the pulp, as well as the results of analysis of the solid residue after
biooxidation and cyanidation, the community developed at 40 degrees C exhibited
the highest rate of oxidation. The degree of gold recovery at 35, 40, and 45
degrees C was 89.34, 94.59, and 83.25%, respectively. At 40 degrees C, the
highest number of microbial cells (6.01 x 10(9) cells/mL) was observed. While
temperature had very little effect on the species composition of microbial
communities, except for the absence of Leptospirillum ferriphilum at 35 degrees
C, the shares of individual species in the communities varied with temperature.
Relatively high numbers of Sulfobacillus thermosulfidooxidans, the organism
oxidizing iron and elemental sulfur at higher rates than other acidophilic
chemolithotrophic species, were observed at 40 degrees C.
PMID- 25844445
TI - [Cryptomonad alga Rhodomonas sp. (Cryptophyta, Pyrenomonadaceae) bloom in the
redox zone of the basins separating from the White Sea].
AB - Bloom of a cryptomonad alga Rhodomonas sp. (Cryptophyta, Pyrenomonadaceae) was
observed in the chemocline of saline basins separating from the White Sea,
resulting in red coloration of the relevant water layer. According to the
sequence of the 18S nuclear rRNA gene, this species was identical to Rhodomonas
sp.RCC2020 (GenBank accession no. JN934672) from the Beaufort Sea. The presence
of the red layer formed by mass development of Rhodomonas sp. is considered as an
indicator of a certain stage of separation of a basin from the sea.
PMID- 25844446
TI - [Microbial communities of the discharge zone of oil- and gas-bearing fluids in
low-mineral Lake Baikal].
AB - At the site of natural ingress of oil microbial diversity in the Central Baikal
bottom sediments differing in the chemical composition of pore waters was studied
by molecular biological techniques. The sediments saturated with oil and methane
were found to contain members of 10 bacterial and 2 archaeal phyla. The oxidized
sediment layer contained methanotrophic bacteria belonging to the
Alphaproteobacteria, which had a specific structure of the pmoA gene and
clustered together with uncultured methanotrophs from cold ecosystems. The upper
sediment layer contained also oil-oxidizing bacteria and the alkB genes most
colsely related to those of Rhodococcus. The microbial community of reduced
sediments exhibited lower diversity and was represented mostly by the organisms
involved in hydrocarbon biodegradation.
PMID- 25844447
TI - [Isolation of a divergent strain of Candida saitoana from the Anyui mummy of a
steppe bison (Bison priscus)].
PMID- 25844448
TI - [In memorium I. S. Kulaev].
PMID- 25844449
TI - [Antenna replacement in the evolutionary origin of chloroplasts].
AB - Endosymbiotic origin of chloroplasts from unicellular cyanobacteria is presently
beyond doubt. Oxygenic photosynthesis is based on coordinated action of two
photosystems (PS), PS I and PS II, cooperating with several variants of the
pigment antenna. In cyanobacteria, red algae, and glaucophytes, phycobilisomes
(PBS) act as antennae, while in terrestrial plants, as well as most macro- and
microalgae antennae are formed by chlorophyll a/b- and chlorophyll a/c-containing
proteins. Advantages and disadvantages of the PBS antenna compared to other light
gathering complexes form the basis for adaptive variations of the antenna in the
course of development of eukaryotic photosynthesis. During the evolution of the
"green" and "chromophyte" lineages of the chloroplasts, PBS, in spite of their
optimal features of light absorption,were replaced by chlorophyll a/b- and
chlorophyll a/c-containing light-gathering complexes. Development of the cell
wall associated with limited motility and with tissue formation in photosynthetic
eukaryotes were the factors responsible for the antenna shift. The subsequent
redistribution of cell resources in favor of cellulose biosynthesis required
increased for CO2 consumption, higher PS II levels, and greater number and
density of the thylakoids in the chloroplasts, got incompatible with the energy
consuming and overly large PBS antenna.
PMID- 25844450
TI - [ATP pool and bioluminescence in psychrophilic bacteria Photobacterium
phosphoreum].
AB - Bioluminescence activity and ATP pool were investigated in the culture of
psychrophilic bacteria Photobacterium phosphoreum collected-from the exponential
and stationary growth phases, as well as immobilized in polyvinyl alcohol (PVA)
cryogel. In liquid culture, ATP pool remained at an almost a constant level
throughout the luminescence cycle (over 100 h). The ATP pool in the stationary
phase and PVA-immobilizedl cells remained constant throughout their incubation in
the medium (over 200 h) and in 3% NaCl solution (over 100 h): Quantitative
assessment of integral photon yield and ATP pool indicated that bioluminescence
decay in growing or stationary cells was not caused by limitation by the energy
substrates of the luciferase reaction. Kinetic and quantitative parameters of
emission activity and ATP pool excluded the possibility of formation of the
aldehyde substrate for luciferase via reduction of the relevant fatty acids in
NADPH and ATP-dependent reductase reaction and its oxidation in the monooxygenase
reaction. Our results indicate that the aliphatic aldehyde is not utilized in the
process of light emission.
PMID- 25844451
TI - [metabolism of the phase variants of the phototrophic bacterium Rhodobacter
sphaeroides].
AB - Growth, bacteriochlorophyll a content, electron transport chain (ETC), and
activities of the tricarboxylic acid (TCA) cycle enzymes were studied in R and M
phase variants of Rhodobactersphaeroides cells grown anaerobically in the light
and aerobically in the dark. Under all cultivation conditions tested,
bacteriochlorophyll a content was 2-3 times lower in the cells of the M. variant
compared to the R variant, which therefore was predominant in the cultures grown
in the light. In both variants, activity of all TCA cycle enzymes was higher for
the cells grown in the dark under aerobic conditions. When grown aerobically in
the dark, the R variant, unlike the M variant, did not contain cytochrome aa3,
acting as. cytochrome c oxidase, in its ETC. An additional point of coupling the
electron transfer to the generation of the proton gradient al the cytochrome aa3
level provided for more efficient oxidation of organic substrates, resulting in
predominance of the M variant in the cultures grown in the dark under aerobic
conditions.
PMID- 25844452
TI - [Characterization of the lipopolysaccharides of serogroup II Azospirillum].
AB - Lipopolysaccharides of six Azospirillum strains (A. brasilense SR50, SR80, SR88,
SR109, SR111, SR115, and A. lipoferum SR 42) isolated from the rhizosphere of
cereal plants of Saratov oblast, Russia and assigned to serogroup II by
serological analysis were studied. In the lipid A fatty acid composition, the
lipopolysaccharides under study were similar to those of other Azospirillum
strains and were characterized by predominance of 3-hydroxytetradecanoic, 3
hydroxyhexadecanoic, and octadecenoic acids. Monosaccharide analysis of the O
specific polysaccharides (including determination of the absolute configurations,
methylation analysis, and one- and two-dimensional NMR spectroscopy) revealed the
presence of two types of repeating units in varying ratios. High degree of
serological similarity between the strains under study was shown to result from
the presence of repeating units with identical structure in their O antigens.
PMID- 25844454
TI - [Changes in growth patterns and intracellular calcium concentrations in
aspergillus awamori treated with amphotericin B].
AB - Growth patterns and intracellular Ca2+ concentrations in the mutant strain
Aspergillus awamori 66A, containing a recombinant aequorin gene were studied in
the presence of a permeabilizing fungicidal agent amphotericin B. The cell
response, i.e., changes in the growth and development of the fungus (initiation
of spore germination, mycelial growth, and intensity ofsporulation) was dose
dependent. Low concentrations of amphotericin B (2.5 microM) stimulated spore
germination: the number of germinating spores was 2-3 times higher than in the
control (without the fungicide). At higher amphotericin concentrations (20
microM) spore germination was inhibited. Amphotericin B had a dose-dependent
effect on mycelial growth and sporulation intensity on solid Vogel medium.
Intracellular Ca2+ concentrations in the presence of amphotericin B were
investigated using the luminescence of the photoprotein aequorin. High
concentrations of amphotericin B (10 and 20 microM) were shown to cause an
instantaneous increase in Ca2+ concentrations, compared to the control and lower
amphotericin concentration (2.5 microM). Ca2+ concentrations remained elevated
throughout the experiment and correlated with the inhibition of mycelial growth
and development.
PMID- 25844453
TI - [Relation between ligninolytic and phospholipase activities in the fungus
Lentinus tigrinus].
AB - Effect of hydrocortisone, NaF, and FeSO4 on ligninolytic and phosphatase activity
of the fungus Lentinus (Panus) tigrinus VKM F-3616D was investigated,
Hydrocortisone and NaF were shown to inhibit the enzymes of the ligninolytic
complex-laccase (EC 1.10.3.2), secretory peroxidase (EC 1.11.1.7), and Mn
peroxidase (EC 1.11.1.13). FeSO4 exhibited no significant effect on the activity
of these enzymes. Decreased activity of the enzymes of the ligninolytic complex
was associatedwith inhibition of the activity and changes in the substrate
specificity of phospholipase A2 (EC 3.1.1.4) in the presence of hydrocortisone of
NaF. Cultivation of L. tigrinus in the presence of these compounds resulted in
higher affinity of this enzyme to saturated fatty acids, while in the control and
in the presence of FeSO4 affinity to unsaturated fatty acids was higher.
PMID- 25844455
TI - [New antibiotics produced by Bacillus subtilis strains].
AB - Two Bacillus subtilis strains isolated from the fruiting body of a basidiomycete
fungus Pholiota squarrosa exhibited a broad range of antibacterial activity,
including those against methicillin-resistant Staphylococcus aureus INA 00761
(MRSA) and Leuconostoc mes6nteroides VKPM B-4177 resistant to glycopep-> tide
antibiotics, as well as antifungal activity. The strains were identified as
belonging to the "B. subtilis" com- plex based on their morphological and
physiological characteristics, as well as by sequencing of the 16S rRNA gene
fragments. Both strains (INA 01085 and INA 01086) produced insignificant amounts
of polyene antibiotics (hexaen and pentaen, respectively). Strain INA 01086
produced also a cyclic polypeptide antibiotic containing Asp, Gly, Leu, Pro, Tyr,
Thr, Trp, and Phe, while the antibiotic of strain INA 01085 contained, apart from
these, two unidentified nonproteinaceous amino acids. Both polypeptide
antibiotics were new compounds efficient against gram-positive bacteria and able
to override the natural bacterial antibiotic resistance.
PMID- 25844456
TI - [Comparison of biochemical and molecular genetic approaches for identification of
environmental strains].
AB - In order to confirm the taxonomic position of environmental strains determined
based on their biochemical, cultural, andmorphological characteristics, molecular
genetic identification was carried out. A number of problems in identification of
microorganisms were shown to be associated with contamination of the cultures in
the course of isolation. Advantages of a comprehensive approach, combining 16S
rRNA gene sequencing with a set of biochemical, cultural, and morphological
parameters; for identification of microorganisms isolated from environmental
objects and clinical samples are discussed.
PMID- 25844457
TI - [Roseibacula alcaliphilum gen. nov. sp. nov., a new alkaliphilic aerobic
anoxygenic phototrophic bacterium from a meromictic soda Lake Doroninskoe (East
Siberia, Russia)].
AB - A bacterial strain De was isolated from the surface water layer of the meromictic
soda lake Doroninskoe. When grown in the dark, it formed-pink colonies on agar
media. The cells were nonmotile, contained bacteriochlorophyll a and carotenoids.
Stationary-phase cells contained intracellular vesicular membranes similar to the
membranes of the photosynthetic apparatus of some ndnsulfur purple bacteria.
Aerobic growth did not occur. Sucrose, citrate, mannitol, sorbitol, case in
hydrolysate,and yeast extract were the preferable substrates for aerobic growth,
Xylose, lactose, aspartate, benzoate, malate, malonate, succinate, tartrate,
formate, fumarate, glycerol, methanol, and ethanol were not utilized; Growth
occurred at up to 50.g/L NaCl (optimum at 5 g/L) and pH 9.8. According to the 16S
rRNA gene sequencing, similarity between the isolate and the known alkaliphilic
genera of nonsulfur purple bacteria (Rhodobaca) and of aerobic anoxygenic
phototrophic bacteria (Roseinatronobacter) was 96%, which was sufficient for
description ofa new genus of aerobic anoxygenic phototrophic bacteria. The name
Roseibacula alcaliphiluin gen. nov., sp. nov. was, proposed for the isolate.
PMID- 25844458
TI - [Promising microbial consortia for producing biofertilizers for rice fields].
AB - Two cyanobacterial cultures from rice paddies of Kyzylorda region, Kazakhstan
were isolated and characterized: Anabaena variabilis and Nostoc calsicola. Based
on these cultures, new consortia ofcyanobacteria, microalgae and Azotobacter were
developed: ZOB-1 (Anabaena variabilis, Chlorella vulgaris, and Azotobacter sp.)
and ZBOB-2 (Nostoc calsicola, Chlorella vulgaris, and Azotobacter sp.). High
growth rate and photosynthetic activity of microalgae were observed in these
consortia. The active consotrium ZOB-1 was selected, which improvd germination
and growth of rice plants. ZOB-1 was recommended as a biostimulator and
biofertilizer for crops.
PMID- 25844459
TI - [Archaeal diversity in permafrost deposits of Bunger Hills Oasis and King George
Island (Antarctica) according to the 16S rRNA gene sequencing].
AB - Archaeal communities of permafrost deposits of King George Island and Bunger
Hills Oasis (Antarctica) differing in the content of biogenic methane were
analyzed using clone libraries of two 16S rRNA gene regions. Phylotypes belonging
to methanogenic archaea were identified in all horizons.
PMID- 25844460
TI - [Anoxygenic phototrophic bacteria from microbial communities of Goryachinsk
Thermal Spring (Baikal Area, Russia)].
AB - Species composition of anoxygenic phototrophic bacteria in microbial mats of the
Goryachinsk thermal spring was investigated along the temperature gradient. The
spring belonging to nitrogenous alkaline hydrotherms is located at the shore of
Lake Baikal 188 km north-east from Ulan-Ude. The water is of the sulfate-sodium
type, contains trace amounts of sulfide, salinity does not exceed 0.64 g/L, pH
9.5. The temperature at the outlet of the spring may reach 54 degrees C. The
cultures of filamentous anoxygenic phototrophic bacteria, nonsulfur and sulfur
purple bacteria, and aerobic anoxygenic phototrophic bacteria were identified
using the pufLM molecular marker. The fmoA marker was used for identification of
green sulfur bacteria. Filamentous cyanobacteria predominated in the mats, with
anoxygenic phototrophs comprising a minor component of the phototrophic
communities. Thermophilic bacteria Chloroflexus aurantiacus were detected irn the
samples from both the thermophilic and mesophilic mats. Cultures ofnonsulfur
purple bacteria similar to Blastochloris sulfoviridis and Rhodomicrobium
vannielii were isolatd from the mats developing at high (50.6-49.4 degrees C) and
low temperatures (45-20 degrees C). Purple sulfur bacteria Allochromatium sp. and
Thiocapsa sp., as well as green sulfur bacteria Chlorobium sp., were revealedin
low-temperature mats. Truly thermophilic purple and gree sulfur bacteria were not
found in the spring. Anoxygenic phototrophic bacteria found in the spring were
typical of the sulfuret communities, for which the sulfur cycle is mandatory. The
presence of aerobic bacteriochlorophylla-containing bacteria identified as
Agrobacterium (Rhizobium) tumifaciens in the mesophilic (20 degrees C) mat is of
interest.
PMID- 25844461
TI - [Population structure of the clover rhizobia Rhizobium leguminosarum bv. trifolii
upon transition from soil into the nodular niche].
AB - High-throughput sequencing of the amplicon gene library revealed variations in
the population structure of clover rhizobia (Rhizobium leguminosarum bv.
trifolii) upon transition from soil into the root nodules of the host plant
(Trifolium-hybridum). Analysis of rhizobial-diversity using the nodA gene
revealed 3258 and 1449 nucleotide sequences (allelic-variants) for the soil and
root nodule population, respectively. They were combined into 29 operational
taxonomic units (OTU) according to the 97% identity level; 24 OTU were. foundin
the soil population, 12 were present in the root nodulepopulation, and 7 were
common. The predominant OTE13 (77.4 and 91.5% of the soil and root nodule
populations, respectively) contained 155 and -200 variants of the soil and root
nodule populations, respectively, with the nucleotide diversity increasing
significantly upon the "soil-->root" transition. The "moving window" approach was
used to reveal the sites of the nodA gene in which polymorphism, including that
associated with increased frequency of non-synonymous substitution frequency,
increased sharply upon transition from soil into root nodiles. PCR analysis of
the IGS genotypes of individual strains revealed insignificant changes in
rhizobial diversity upon transition from soil into root nodules. These results
indicate that acceleration of rhizobial evolutioin in the course of symbiosis may
be associated with development of highly polymorphic virulent:subpopulations
subjected to directional selection in the "plant-soil" system.
PMID- 25844462
TI - [Ca2+ signaling in prokaryotes].
AB - The role of Ca2+ ions in the regulation of motility, cell cycle, and division of
prokaryotes is dis- cussed, as well as their involvement in pathogenesis of come
infectious diseases. The structural and functional organization of the
prokaryotic Ca2+ signal system and the mechanisms of Ca2+ membrane transport and
homeostasis are described. Special attention is paid to the role of Ca2+ cation
channels, Ca2+ transporters, and Ca2+ -binding proteins in the regulation of the
intercellular Ca2+ concentration.
PMID- 25844463
TI - [Synthesis and localization of L-lactate oxidase in yeasts].
AB - Conditions for L-lactate oxidase synthesis by the yeast Yarrowia lpolytica were
investigated. The enzyme was found to be synthesized during growth on L-lactate
in the exponential growth phase. L-lactate oxidase synthesis was observed, also
on glucose after adaptation to stress conditions (oxidative or thermal stress) r
during the stationary growth phase after glucose consumption. The cells grown on
L-lactate exhibited high levels of antioxidant enzymes (catalase, superoxide
dismutase, glucose-6-phosphate dehydrogenase, and glutathione reductase), which
exceeded those of glucose-grown cells. The ultrastructure of L-lactate-grown
cellsand of those grown on glucose and adapted to various stress.conditions was
also found to besimilar, with increased mitochondria, elevated number and size
ofperoxisomes, and formation of lipid and polyphosphate inclusions. In order to
determine the intracellular localization of L-lactate oxidase, the cells were
disintegrated by the lytic enzyme complex from Helix pomatia. Centrifugation of
the homogenate in Percoll gradient resulted in the isolation of purified
fractions of the native mitochondria and peroxisomes. L-Lactate oxidase was shown
to be localized in peroxisomes.
PMID- 25844464
TI - [Formation of organic acids by fungi isolated from the surface of stone
monuments].
AB - Capacity of the fungi isolated from the surface of stone monuments for acid
formation was studied in cultures under various carbon sources and cultivation
conditions. The composition of organic nutrients was adjusted according to the
results of investigation of the surface layers from the monuments in urban
environment. The primary soil formed at the surface of the stone monuments under
urban conditions was shown to contain a variety of carbon and nitrogen sources
and is a rich substrate for fungal growth. Oxalic acid was produced by fungi
grown on media with various concentrations of sugars, sugar alcohols, and organic
acids. Malic, citric, fumaric, and succinic acids were identified only at
elevated carbohydrate concentrations, mostly in liquid cultures. Oxalic acid was
the dominant among the acids produced by Aspergillus niger at all experimental
setups. Unlike A. niger, the relative content of oxalic acid produced by
Penicillium citrinum decreased at high carbohydrate concentrations.
PMID- 25844465
TI - [Biological activity of fungi from the phyllosphere of weeds and wild herbaceous
plants].
AB - Antimicrobial, phytotoxic, and insecticidal activity of 30 fungal isolates
obtained from leaves of weeds and wild herbaceous plants was assessed.
Antibacterial, antifungal, phytotoxic, and insecticidal activity was found in
over 50, 40, 47, and 40% of the isolates, respectively. These findings may be
important for toxicological assessment of potential mycoherbicides, as well as
provide a basis for investigation of the patterns of development of phyllosphere
communities affected by fungal metabolites.
PMID- 25844466
TI - [Auxin production by Klebsiella planticola strain TSKhA-91 and Its Effect of
development of cucumber (Cucumis sativus L.) Seeds].
AB - Capacity of Klebsiella planticola strain TSJhA-91 for synthesis of indolyl-3
acetic acid (IAA) and other auxins was studied. The qualitative and quantitative
composition of these compounds depends on the presence of exogeneous tryptophan
and on the nitrogen source. The highest IAA yield was obtained at the stationary
phase of growth. Addition of L-tryptophan to the medium resulted in a significant
increase (up to 85.5 microg/mL) of auxin biosynthesis, especially in the presence
of nitrates. Thin-layer chromatography revealed that the indole-3-acetamide
pathway was not active in this strain. The biological activity of auxins was
confirmed by plant assay with the kidney bean cuttings; the height of root
formation and rdot number increased 16- and 6-fold, respectively. Under
conditions of low-temperature stress, protective effect of K. planticola TSKhA-91
on development of cucumbers (Cucumissativus L.) seeds, including stimulation of
germi- nation and root formation by its seeds were shown.
PMID- 25844467
TI - [Thermoacidophilic micirobial community oxidizing the gold-bearing flotation
concentrate of a pyrite-arsenopyrite ore].
AB - An aboriginal community of thermophilic acidophilic chemolithotrophic
microorganisms (ACM) was isolated from a sample of pyrite gold-bearing flotation
concentrateat 45-47 degrees C and pH 1.8-2.0. Compared to an experimental
thermoacidophilic microbial consortium formed in the course of cultivation in
parallel bioreactors, it had lower rates of iron leaching and oxidation, while
its rate of sulfur oxidation was higher. A new thermophilic acidophilic microbial
community was obtained by mutual enrichment with the micioorganisms from thie
experimental and aboriginal communities during oxidation of sulfide ore flotation
concentrate at 47 degrees C. The dominant bacteria of this new ACM community were
Acidithiobacillus caldus strains (the most active sulfur oxidizers) and
Sulfobacillus thermotolerans strains (active oxidizers of both iron and sulfur),
while iron-oxidizing archaea of the family Ferroplasmaceae and heterotrophic
bacteria Alicyclobacillus tolerans were the minor components. The new ACM
community showed promise for leaching/oxidation of sulfides from flotation
concentrates at high pulp density (S:L = 1:4).
PMID- 25844468
TI - [Optimization of bioleaching and oxidation of gold-bearing pyrite-arsnopyrite ore
concentrate in batch mode].
AB - Biooxidation of refractory gold-bearing pyrite-arsenopyrite flotation concentrate
was optimized and aburidance of predominant groups in the community
ofthermophilic acidophilic chemolithotrophic microorganisms at various stages
ofbioleaching was determined. The optimal parameters for growth and
leaching/oxidation of the mineral components of the concentrate were pSH 1.4, 1.6
1.8; 47.5 degrees C; and the following salt concentrations in the liquid phase
(g/L): K2HPO4.3H2O, 0.53; (NH4)2SO4, 1.6 and MgSO4.7H2O, 2.5 (or (NH4)2SO4, 1.23;
ammophos, 0.41; KOH, 0.1) with 0.03% yeast extract. The optimal conditions
resulted in high growth rate, high levels of iron andarsenic leaching, of Fe2+
and S(2-)/S0 oxidation, and predominance of Acidithiobacillus caldus,
Sulfobacillus spp., and Ferroplasma spp. in the community.
PMID- 25844469
TI - [transversion of cell polarity from Bi- to multipolarity is the mechanism
determining multiple spore formation in Anaerobacter polyendosporus PS-1T].
AB - The number of spores formed in a single cell ofAnaerobacterpolyendosporus PS-1T
is significantly influenced by the composition of nutrient media. Depending on
carbohydrate concentration in synthetic medium, the number of spores may vary
from one-two to five-seven. Investigation of spore formation by fluorescence and
electron microscopy revealed that on media with 0.5-1.0% glucose or galactose
most of the vegetative cells remained rod-shaped after cessation of cell division
in the culture. Their nucleoids were localized at cell poles close to the polar
site of the cytoplasmic membrane. Forespores were formed at one or both of these
poles. A satellite nucleoid (operator) was detected close to each forespore. In
the variant with bipolar organization of mother cells only one or two spores per
cell were formed. In the second variant of cultivation, when the cells grew at
low galactose concentrations (0.1-0.3%), most of the vegetative cells increased
in volume and became oval or spherical after cessation of cell division in the
culture. Epifluorescence microscopy with nucleic acids-specific fluorochromes
(DAPI and acridine orange) revealed the presence of multiple (six to nine)
nucleoids in these cells. The nucleoids were located at the cell periphery in
close contact with the cytoplasmic membrane. These nucleoids became the centers
(poles) for forespore formation. Thus, in the early stationary phase transversion
from bipolar to multipolar cells occurred during the early stationary phase.
Cessation of cell division combined with continuing replication of the nucleoids
resulted in formation on multinuclear cells. The multiplicity of nucleoides and
multipolarity of these cells were prerequisites determining endogenous
polysporogenesis, occurring as synchronous formation of three to seven twin
spores in a number of the oval and spherical cells.
PMID- 25844471
TI - [Comparison of the fungal complexes of the Japanese scallop Mizuhopecten
yessoensis (Jay, 1856) from different areas of the Peter the Great Bay, Sea of
Japan].
AB - Mycological investigation of the Japanese scallop Mizuhopecten yessoensis (Jay)
(Bivalvia) collected in different areas of the Peter the Great Bay, Sea of Japan,
was carried out. A total of 72 species of filamentous fungi belonging to 30
genera of ascomycetes, anamorphous fungi, and zygomycetes was isolated from the
internal organs of the scallop. The species.diversity of mycelial fungi in the
internal organs, especially of members of the generaAspergillus, Penicillium,
Cladosporium, and Chaetomium, was found to increase in polluted coastal waters.
PMID- 25844470
TI - [Diversity of diazotrophs in the sediments of hypersaline salt and soda lakes
analyzed with the use of the nifH gene as a molecular marker].
AB - Phylogenetic analysis of the nifH genes, encoding the Fe protein of the
nitrogenas enzymatic complex, was carried out for pure cultures of anoxygenic
phototrophic bacteria of diverse origin, as well as for heterotrophic
alkaliphilic sulfate reducers isolated from saline and soda lakes. Topology of
the nitrogenase tree correlated with that of the 16S rRNAgene tree to a
considerable degree; which niade it possible to use the nifH gene as a molecular
marker for investigation of diazotrophic bacterialcommunities in silty sediments
of saline and sodalakes. Although diazotrophs were revealed in all
environmentalsamples, their phylogenetic diversity was relatively low. Sulfate
reducing deltaproteobacteria and photo- and chemotrophicgammaproteobacteria were
predominant in samples integrated over sediment thickness. Analysis of samples
fromthe upper sediment layers revealed predominance of phototrophic diazotrophs
of various phyla, including purple sulfur and nonsulfur proteobacteria, green
nonsulfur bacteria, heliobacteria; and cyanobacteria. Some phylotypes could not
be identified, probably indicating the presence of bacterial groups which have
not yet been studied by conventional microbiological techniques.
PMID- 25844472
TI - [Report of Quambalaria cyanescens associated with birch].
AB - Long-term microbiological investigation of the pollen of silver birch (Betula
pendula) in the Mos- cow, and Moscow region areas revealed that: almost one-third
of the analyzed samples, contained the fungus identified by morphological,
cultural, and molecular genetic techniques as Quambalaria cyanescens (de Hoog &
G. A. de Vries) Z.W. de Beer, Begerow & R. Bauer. This species was previously
known mostly as a syrmbiont of tropical plants of the generaEucalyptus and
Cortyminbia and has not been isolated in Russia. We revealed a close association
between Quambalaria cyanescens and silver birch. The micromycete was regulaly
detected in pollen samples, as well as on the.inside and outside of the aments,
on the surface of leaves and branches. It was never isolated from other plant
species in the investigated area. The data on the morphological and cultural
characteristics of the fungus, its cell ultrastructure, and occurrence are
presented, as well as the phylogenetic analysis of the isolated strains.
PMID- 25844473
TI - [Microbial composition of the activated sludges of the Moscow wastewater
treatment plants].
AB - The contribution of the major technologically important microbial groups
(ammonium- and nitrite-oxidizing, phosphate-accumulating, foam-inducing, and
anammox bacteria, as well as planctomycetes and methanogenic archaea) was
characterized for the aeration tanks of the Moscow wastewater treatment
facilities. FISH investigation revealed that aerobic sludges were eubacterial
communities; the metabolically active archaea contributed insignificantly. Stage
II nitrifying microorganisms and planctomycetes were significant constituents of
the bacterial component of activated sludge, with Nitrobacter spp. being the
dominant nitrifier. No metabolically active anammox bacteria were revealed in the
sludge from aeration tanks. The sludge from the aeration tanks using different
wastewater treatment technologies were found to differ in characteristics.
Abundance of the nitrifying and phosphate-accumulating bacteria in the sludges
generally correlated with microbial activity, in microcosms and with efficiency
of nitrogen and phosphorus removal from wastewater. The highest microbial numbers
and activity were found in the sludges of the tanks operating according to the
technologies developed in the universities of Hanover and Cape Town. The
activated sludge from the Novokur yanovo facilities, where abundant growth of
filamentous bacteria resulted in foam formation, exhibited the lowest activity
The group of foaming bacteria included Gordonia spp. and Acinetobacter spp.,
utilizing petroleum and motor oils, Sphaerotilus spp. utilizing unsaturated fatty
acids, and Candidatus 'Microthrix parvicella'. Thus, the data on abundance and
composition of metabolically active microorganisms obtained by FISH may be used
for the technological control of wastewater treatment.
PMID- 25844474
TI - [Molecular genetic identification of microcystin-producing cyanobacterial taxa in
Lake Nero (Russia)].
PMID- 25844475
TI - [Correction of hydrodynamic disorders in severe alcohol poisoning in adolescent].
AB - OBJECTIVE: To improve the results of treatment of children with severe alcohol
poisoning as a result of investigation of water sectors of the body. METHODS: The
study included 54 patients aged from 13 to 15 years with a diagnosis of acute
severe alcohol poisoning. All patients were divided into three groups. At the
initial examination was determined the concentration of alcohol in saliva using
Express-test "Alkoskan." Bioimpedance analysis was performed; water sectors of
the body were investigated by analyzer of the balance of water sectors ABC-01
"Medass." The study was conducted at the time of admission, after 12, 24 and 48
hours. RESULTS: In severe alcohol poisoning at the time of admission, it was
revealed a reduction of the fluid in all studied sectors. The most effective
compensation of liquid was observed in groups, where was used combination therapy
included intravenous fluids based 4.0 ml/kg/hour. CONCLUSION: The treatment of
severe alcohol poisoning should include fluid resuscitation about 4 ml/kg/hour.
This capacity of medical care give the ability to correct adequately the water
sectoral disturbances already in the first 12 hours of hospitalization, and the
inclusion to the basic therapy reamberine can contribute more effective
replenishment of water sectors.
PMID- 25844476
TI - [Effect of anesthesia in prevention of postoperative nausea and vomiting after
surgical interventions in the nasal cavity and nasopharynx in children].
AB - The article deals with results of studying of anesthesia effects on the frequency
of postoperative nausea and vomiting during surgical interventions in the nasal
cavity and nasopharynx in children. We investigated the incidence of
postoperative nausea and vomiting in 100 patients aged 2 to 17 years (ASA I-II),
who underwent surgery in the nasal cavity and nasopharynx. The results showed
that the anesthesia by sevoflurane with nitrous oxide, local anesthetic lidocaine
4 mg/kg, not more than 200 mg by nebulizer was accompanied by the development of
postoperative nausea and vomiting in 4% of cases. In another hand, anesthesia by
sevoflurane, nitrous oxide and fentanyl 2-3 mg/kg was accompanied with nausea and
vomiting in 18% cases. Analysis of the results showed that the frequency of
postoperative nausea and vomiting after anaesthesia without fentanyl by 14% lower
than with fentanyl. The nausea and vomiting started within the first hour after
surgery in majority number of cases (50-77.7%).
PMID- 25844477
TI - [Causes of mortality and severity of state in newborns with inborn defects].
AB - There is significant decrease in mortality rate of newborns with system
dysfunction after development of perinatal centers in Russia. But in children
with small gestational age and severe inborn defects the mortality rate is still
high. Main causes of mortality and severity are: multiorgan failure, immaturity,
infections (virus and/or bacteria, fungi). Severity of patient's condition
strongly correlates with inflammation markers. Other factors effecting on
mortality rate and probability of complication in postoperative period, are
appearance of resistant microbes in premature babies and inability to total
elimination of infectious source.
PMID- 25844478
TI - [Enteral oxygenation in complex treatment of anaerobic septic shock in postpartum
woman].
AB - Purpose of the clinical case demonstration is to attract the professionals'
attention to the method of enteral oxygen therapy successfully used in the
complex intensive therapy of septic shock in young postpartum woman.
PMID- 25844480
TI - Radical cyclization of epoxy vinyl- and allylsulfones promoted by titanocene
chloride.
AB - A titanocene-mediated intramolecular radical addition of different epoxy vinyl-
and allylsulfones has been achieved. Five- and six-membered ring products were
obtained in good to excellent yields in the presence of both 2.2 and 0.2 equiv of
Cp2TiCl. A novel double-activation strategy allowed us to achieve small-size
rings such as cyclobutanes and cyclopropanes.
PMID- 25844481
TI - In Vitro Studies on Degradation of Gamma-L-Glutamyl-L-Cysteine and Gamma-L
Glutamyl-D-Cysteine in Blood: Implications for Treatment of Stroke.
AB - Treatment for ischemic stroke involves a thrombolytic agent to re-establish blood
flow in the brain. However, delayed reperfusion may cause injury to brain
capillaries. Previous studies indicate that the antioxidant gamma-L-glutamyl-L
cysteine (gamma-Glu-Cys) contributes to reducing reperfusion injury to the
cerebral vasculature in rats, when administered intravascularly. To determine the
stability of gamma-Glu-Cys in blood, the peptide was incubated in rat serum in
vitro, and its degradation was quantified by high-pressure liquid chromatography.
The half-time (t1/2) for degradation of gamma-Glu-Cys was 11 +/- 1 minute (mean
+/- SD, n = 3). A similar pattern of degradation was observed when gamma-Glu-Cys
was incubated in the presence of human plasma (t1/2 = 17 +/- 8 minutes, n = 3).
In a second series of experiments, degradation of an analog (gamma-Glu-D-Cys) was
tested in rat serum and found to be more stable than the native molecule. The
initial velocity for degradation of gamma-Glu-D-Cys (0.12 +/- 0.02 mM/min; mean
+/- SD, n = 3) was significantly (P = 0.006) less than that of gamma-Glu-Cys
(0.22 +/- 0.03 mM/min; mean +/- SD, n = 3). Furthermore, an in vitro assay
indicated that the analog has as an oxidative capacity that equals that of the
original peptide in the presence of rat serum and human plasma. Finally, both
peptides were found to be similarly effective in preventing lysis of intact cells
using in vitro assays. These studies show that gamma-Glu-Cys remains intact in
blood for several minutes, and the analog gamma-Glu-D-Cys may be a more stable,
but similarly effective antioxidant.
PMID- 25844479
TI - The effect of ghrelin upon the early immune response in lean and obese mice
during sepsis.
AB - INTRODUCTION: It is well established that obesity-related hormones can have
modulatory effects associated with the immune response. Ghrelin, a hormone mainly
derived from endocrine cells of the gastric mucosa, regulates appetite, energy
expenditure and body weight counteracting leptin, a hormone mainly derived from
adipocytes. Additionally, receptors of both have been detected on immune cells
and demonstrated an immune regulatory function during sepsis. METHODS: In the
present study, the effect of peripheral ghrelin administration on early immune
response and survival was investigated with lean mice and mice with diet-induced
obesity using cecal ligation and puncture to induce sepsis. RESULTS: In the obese
group, we found that ghrelin treatment improved survival, ameliorated
hypothermia, and increased hyperleptinemia as compared to the lean controls. We
also observed that ghrelin treatment divergently regulated serum IL-1beta and TNF
alpha concentrations in both lean and obese septic mice. Ghrelin treatment
initially decreased but later resulted in increased bacteriaemia in lean mice
while having no impact upon obese mice. Similarly, ghrelin treatment increased
early neutrophil oxidative burst while causing a decrease 48 hours after sepsis
inducement. CONCLUSION: In conclusion, as the immune response to sepsis
temporally changes, ghrelin treatment differentially mediates this response.
Specifically, we observed that ghrelin conferred protective effects during the
early phase of sepsis, but during the later phase deteriorated immune response
and outcome. These adverse effects were more pronounced upon lean mice as
compared to obese mice.
PMID- 25844482
TI - Efficacy of Bisphosphonates on Bone Mineral Density and Fracture Rate in Patients
With Osteogenesis Imperfecta: A Systematic Review and Meta-analysis.
AB - Epidemiological evidence suggests that bisphosphonates are the most promising
drugs for patients with osteogenesis imperfecta (OI). However, data on this issue
are controversial. We conducted a meta-analysis to assess the efficacy of
bisphosphonates on bone mineral density (BMD) and fracture rate in patients with
OI. Electronic databases were searched to find relevant studies. Two reviewers
independently identified relevant randomized controlled trials, which evaluated
the efficacy of bisphosphonates in patients with OI. Outcome measures were
fracture incidence and BMD changes in different skeletal sites. A total of 9
randomized controlled trials including 557 patients were identified. Meta
analysis demonstrated a beneficial effect of bisphosphonates on spine BMD Z-score
and area BMD (in grams per square centimeter) %. Patients treated with
bisphosphonates had a lower risk of fracture [risk ratio (RR) = 0.80; 95%
confidence interval (CI): 0.66-0.97] compared with those in control groups. In
children, bisphosphonates were efficacious in reducing fractures (RR = 0.80; 95%
CI: 0.66-0.97), where in adults, bisphosphonates seemed equivalent to placebo in
that respect (RR = 0.82; 95% CI: 0.42-1.59), although no significant difference
was noted between these 2 RRs (test of interaction, z = -0.07; P = 0.94). There
was also no significant difference in reducing fractures between oral and
intravenous bisphosphonates (P = 0.23). This study showed that bisphosphonates
could increase the BMD and reduce the risk of facture in patients with OI. There
was no enough evidence to identify any differences in efficacy between oral and
intravenous bisphosphonates on fracture reduction, as well as between children
and adults.
PMID- 25844483
TI - Vertically aligned sulfur-graphene nanowalls on substrates for ultrafast lithium
sulfur batteries.
AB - Although lithium-sulfur batteries have gained great interest owing to their high
energy density, they lack suitable electrodes capable of rapid charging and
discharging to enable a high power density critical for wide applications. Here,
we demonstrate a simply electrochemical assembly strategy to achieve vertically
aligned sulfur-graphene (S-G) nanowall onto electrically conductive substrates.
Remarkably, in each individual S-G nanowalls, sulfur nanoparticles are
homogeneously anchored in between of graphene layers and ordered graphene arrays
arrange perpendicularly to the substrates, which are favorable for the fast
diffusions of both lithium and electron. Moreover, the hierarchical and porous
structures facilate the effective accommodation of the volume change of sulfur.
As a consequence, a high reversible capacity of 1261 mAh g(-1) in the first cycle
and over 1210 mAh g(-1) after 120 cycles with excellent cyclability and high-rate
performance (over 400 mAh g(-1) at 8C, 13.36 A g(-1)) are achieved with these S-G
nanowalls as cathodes for lithium-sulfur batteries, providing the best reported
rate performance for sulfur-graphene cathodes to date.
PMID- 25844484
TI - Special focus on autophagy.
PMID- 25844485
TI - Retraction of Characterization of hydroxymethylation patterns in the promoter of
beta-globin clusters in murine fetal livers (DOI: 10.1089/dna.2014.2773).
PMID- 25844486
TI - Controllably Interfacing with Ferroelectric Layer: A Strategy for Enhancing Water
Oxidation on Silicon by Surface Polarization.
AB - Silicon (Si) is an important material in photoelectrochemical (PEC) water
splitting because of its good light-harvesting capability as well as excellent
charge-transport properties. However, the shallow valence band edge of Si hinders
its PEC performance for water oxidation. Generally, thanks to their deep valence
band edge, metal oxides are incorporated with Si to improve the performance, but
they also decrease the transportation of carriers in the electrode. Here, we
integrated a ferroelectric poly(vinylidene fluoride-trifluoroethylene) [P(VDF
TrFE)] layer with Si to increase the photovoltage as well as the saturated
current density. Because of the prominent ferroelectric property from P(VDF
TrFE), the Schottky barrier between Si and the electrolyte can be facially tuned
by manipulating the poling direction of the ferroelectric domains. The
photovoltage is improved from 460 to 540 mV with a forward-poled P(VDF-TrFE)
layer, while the current density increased from 5.8 to 12.4 mA/cm(2) at 1.23 V
bias versus reversible hydrogen electrode.
PMID- 25844487
TI - Chemistry and related properties of freshly emitted sea spray aerosol.
PMID- 25844488
TI - Evidence-Based Practice among Romanian Social Workers: Attitudes, Utilization,
and Barriers.
AB - In this article the authors report on a small survey of Romanian social workers
regarding their attitudes toward evidence-based practice (EBP) and thoughts on
the factors affecting its implementation in their clinical work. Eighty social
workers were asked to complete a pen-and-paper questionnaire on their attitudes
toward EBP, the use of research, and perceived barriers on implementation. Social
workers have generally positive attitudes toward EBP. Insufficient time surfaced
as the greatest barrier to successful implementation. Previous training during
academic programs on the EBP foundations was associated with more positive
attitudes and beliefs and also with stronger commitment toward implementation.
Given the constant pressure that the limited resources pose on the social
services, practitioners from the social work field must assure that their clients
will have access to the best available programs and interventions. However, as
the transfer of research into practice appears more complex than EBP suggests,
the authors sought to understand how professionals construct their attitudes,
level of commitment, and barriers.
PMID- 25844489
TI - Selectivity and anti-Parkinson's potential of thiadiazolidinone RGS4 inhibitors.
AB - Many current therapies target G protein coupled receptors (GPCR), transporters,
or ion channels. In addition to directly targeting these proteins, disrupting the
protein-protein interactions that localize or regulate their function could
enhance selectivity and provide unique pharmacologic actions. Regulators of G
protein signaling (RGS) proteins, especially RGS4, play significant roles in
epilepsy and Parkinson's disease. Thiadiazolidinone (TDZD) inhibitors of RGS4 are
nanomolar potency blockers of the biochemical actions of RGS4 in vitro. Here, we
demonstrate the substantial selectivity (8- to >5000-fold) of CCG-203769 for RGS4
over other RGS proteins. It is also 300-fold selective for RGS4 over GSK-3beta,
another target of this class of chemical scaffolds. It does not inhibit the
cysteine protease papain at 100 MUM. CCG-203769 enhances Galphaq-dependent
cellular Ca(2+) signaling in an RGS4-dependent manner. TDZD inhibitors also
enhance Galphai-dependent delta-OR inhibition of cAMP production in SH-SY-5Y
cells, which express endogenous receptors and RGS4. Importantly, CCG-203769
potentiates the known RGS4 mechanism of Galphai-dependent muscarinic bradycardia
in vivo. Furthermore, it reverses raclopride-induced akinesia and bradykinesia in
mice, a model of some aspects of the movement disorder in Parkinson's disease. A
broad assessment of compound effects revealed minimal off-target effects at
concentrations necessary for cellular RGS4 inhibition. These results expand our
understanding of the mechanism and specificity of TDZD RGS inhibitors and support
the potential for therapeutic targeting of RGS proteins in Parkinson's disease
and other neural disorders.
PMID- 25844490
TI - Adjustment enhancer or moderator? The role of resilience in postmigration filial
responsibility.
AB - The current study investigated resilience factors in filial responsibility and
their relationships to adjustment indicators. Young adult immigrants from the
former Soviet Union to Israel (N = 220) completed the Comprehensive Filial
Responsibilities Inventory and 4 proxy measures of adjustment: An adapted version
of the Brief Symptom Inventory, the Satisfaction With Life Scale, the General
Self-Efficacy Scale, and selected items from the General Life Functioning
Inventory. The resilience factors examined included individual characteristics of
Sense of Coherence, Optimism, and perceived social support from an adapted
version of the Multidimensional Scale of Perceived Social Support. In general,
the resilience factors diminished the relationship between filial responsibility
and some of the adjustment indicators. Overall, resilience factors make a strong
and meaningful contribution to young immigrants' adjustment when main effects are
considered. However, the resilience factors did not moderate the effect of filial
responsibility in a protective way. The results contribute to an understanding of
interrelations between postmigration filial responsibility and adjustment.
Implications for social and clinical work with young-adult immigrants who have
experienced filial responsibility in their family of origin are addressed.
PMID- 25844491
TI - Over-time associations among parental self-efficacy, promotive parenting
practices, and adolescents' externalizing behaviors.
AB - Parental self-efficacy (PSE) is defined as parents' beliefs about their abilities
to influence their children in a way that fosters their children's positive
development. Research has shown links among PSE, parenting, and children's
behavior (Jones & Prinz, 2005), but there are still questions concerning the
associations over time. Theory predicts 3 types of processes relevant to these
associations: a PSE-driven process, a parent-behavior-driven process, and a child
driven process. In this study, we tested these processes during early to middle
adolescence using reports from 401 parents (286 mothers, 115 fathers) from 305
families, and their adolescents (Mage = 11.5 years), at 3 time points. Cross
lagged panel models were used to examine the associations among PSE, promotive
parenting practices, and adolescents' externalizing. Results supported a PSE
driven process for mothers within early adolescence. In addition, evidence for
parent-behavior-driven and child-driven processes emerged at different times
within this developmental period.
PMID- 25844492
TI - Prevention effects on trajectories of African American adolescents' exposure to
interparental conflict and depressive symptoms.
AB - The present study investigates the trajectory of children's exposure to
interparental conflict during adolescence, its effects on adolescents'
psychological adjustment, as well as the ability of a family-centered prevention
program to alter this trajectory. A total of 331 African American couples with an
adolescent or preadolescent child participated in a randomized control trial of
the Promoting Strong African American Families program, a newly developed program
targeting couple and cocaregiving processes. Using a multi-informant, latent
growth curve approach, child exposure to interparental conflict during
adolescence was found to be stable over a period of 2 years among families in the
control group, but significantly declined among families in the treatment
condition. Rates of change were significantly different between intervention and
control groups based on parents' report of youth exposure to interparental
conflict, but not for child's report. Structural equation models found trajectory
parameters of interparental conflict predicted changes in adolescent depressive
symptoms, with increasing rates of changes in conflict associated with increases
in adolescent internalizing symptoms over the 2-year duration of the study.
Finally, a significant indirect effect was identified linking treatment, changes
in parents' reports of child exposure to interparental conflict, and adolescent
depressive symptoms. The implications for research and intervention are
discussed.
PMID- 25844493
TI - Two-year outcomes of the Early Risers prevention trial with formerly homeless
families residing in supportive housing.
AB - This article reports 2-year outcomes from a cluster randomized, controlled trial
of the Early Risers (ER) program implemented as a selective preventive
intervention in supportive housing settings for homeless families. Based on the
goals of this comprehensive prevention program, we predicted that intervention
participants receiving ER services would show improvement in parenting and child
outcomes relative to families in treatment-as-usual sites. The sample included
270 children in 161 families, residing in 15 supportive housing sites;
multimethod, multi-informant assessments conducted at baseline and yearly
thereafter included parent and teacher report of child adjustment, parent report
of parenting self-efficacy, and parent-child observations that yielded scores of
effective parenting practices. Data were modeled in HLM7 (4-level model
accounting for nesting of children within families and families within housing
sites). Two years' postbaseline, intent-to-treat (ITT) analyses indicated that
parents in the ER group showed significantly improved parenting self-efficacy,
and parent report indicated significant reductions in ER group children's
depression. No main effects of ITT were shown for observed parenting
effectiveness. However, over time, average levels of parenting self-efficacy
predicted observed effective parenting practices, and observed effective
parenting practices predicted improvements in both teacher- and parent-report of
child adjustment. This is the first study to our knowledge to demonstrate
prevention effects of a program for homeless families residing in family
supportive housing.
PMID- 25844494
TI - Can mindful parenting be observed? Relations between observational ratings of
mother-youth interactions and mothers' self-report of mindful parenting.
AB - Research on mindful parenting, an extension of mindfulness to the interpersonal
domain of parent-child relationships, has been limited by its reliance on self
report assessment. The current study is the first to examine whether
observational indices of parent-youth interactions differentiate between high and
low levels of self-reported mindful parenting. The Iowa Family Interaction Rating
Scales (IFIRS) were used to code interactions between mothers and their 7th grade
youth. Mothers drawn from the top and bottom quartiles (n = 375) of a larger
distribution of self-reported interpersonal mindfulness in parenting (N = 804)
represented clearly defined high- and low-mindful parenting groups. Discriminant
function analysis (DFA) was used to analyze how well 6 composite IFIRS
observational rating variables (e.g., parental warmth, consistent discipline)
discriminated between high and low self-reports of mindful parenting. DFA results
were cross-validated, with statistically significant canonical correlations found
for both subsamples (p < .05). Subsequent independent samples t tests revealed
that group means were significantly different on all 6 IFIRS composite ratings.
Confirmation of the relations between self-report mindful parenting and the
observational ratings was also provided through hierarchical regression analyses
conducted with a continuous predictor of mindful parenting using the full sample.
Thus, the present study provides preliminary evidence for a link between self
reported mindful parenting and observed interactions between parents and youth.
PMID- 25844495
TI - Parental criticism is an environmental influence on adolescent somatic symptoms.
AB - Previous studies have suggested that parental criticism leads to more somatic
symptoms in adolescent children. However, this research has not assessed the
direction of causation or whether genetic and/or environmental influences explain
the association between parental criticism and adolescent somatic symptoms. As
such, it is impossible to understand the mechanisms that underlie this
association. The current study uses the Extended Children of Twins design to
examine whether parents' genes, adolescents' genes, and/or environmental factors
explain the relationship between parental criticism and adolescent somatic
symptoms. Participants came from 2 twin samples, including the Twin and Offspring
Study in Sweden (N = 868 pairs of adult twins and each twin's adolescent child)
and from the Twin Study of Child and Adolescent Development (N = 690 pairs of
twin children and their parents). Findings showed that environmental influences
account for the association between parental criticism and adolescent somatic
symptoms. This suggests that parents' critical behaviors exert a direct
environmental effect on somatic symptoms in adolescent children. Results support
the use of intervention programs focused on parental criticism to help reduce
adolescents' somatic symptoms.
PMID- 25844497
TI - Salivary cortisol responses to household tasks among couples with unexplained
chronic fatigue.
AB - This study examined salivary cortisol levels in couples in which one member had
unexplained chronic fatigue (CF). The couples completed questionnaires and seven
household activities in a laboratory setting and provided salivary cortisol
samples prior to and immediately after the activities, as well as again after
completing additional questionnaires and debriefing. The couples rated their
interactions as similar to those at home, suggesting ecological validity, and
patients with CF experienced the activities as involving more exertion than did
their partners. The multilevel model results indicated that patients with CF had
overall lower cortisol levels and flatter slopes across repeated measurements
than did their significant others. Patients' and significant others' cortisol
concentrations were significantly associated with each other over time.
Furthermore, significant others' cortisol was associated with greater
relationship satisfaction and greater observed rates of patients' illness/pain
behaviors per minute, but patients' levels of cortisol were not associated with
relationship variables. This study is the first to examine cortisol in couples
with CF; the results are discussed in terms of implications for future research.
PMID- 25844496
TI - Marital status, marital quality, and heart rate variability in the MIDUS cohort.
AB - Previous research has shown marital status and marital quality are consistent
predictors of health outcomes, including cardiovascular disease and mortality. To
better understand the relationship among marital status, marital quality, and
cardiovascular health, we examined how marital status and marital quality were
associated with an early indicator of deteriorating cardiovascular health, high
frequency heart rate variability (HF-HRV). This study uses data from the National
Survey of Midlife in the United States (MIDUS) Biomarker Substudy (N = 907) to
examine differences in HF-HRV by traditional marital status categories (married,
divorced, widowed, and never married) as well as further differentiating between
the continuously married and remarried. In addition, links were also examined
between HF-HRV and changes in marital quality (marital satisfaction, support,
strain) among individuals in long-term marriages. No significant differences in
HF-HRV were observed between married persons and those widowed, divorced, and
never married. However, continuously married individuals had higher HF-HRV than
remarried adults. Increases in marital satisfaction and support over 10 years
were associated with higher HF-HRV, whereas increased marital strain over 10
years was associated with lower HF-HRV. Higher HF-HRV among the continuously
married compared with the remarried suggests that previous marital disruptions
may have lasting effects on cardiovascular health or that there may be other
differences between the remarried versus those who remain married to the same
person. Associations between marital quality and HF-HRV suggest that variations
in the quality of one's marriage may affect cardiovascular health.
PMID- 25844498
TI - Self-reports and spouse ratings of neuroticism: perspectives on emotional
adjustment in couples.
AB - Evidence of reciprocal associations between individual emotional adjustment and
the quality of intimate relationships has led to the growing use of interventions
that combine a focus on couple issues with a focus on individual emotional
functioning. In these approaches, spouse ratings of emotional functioning can
provide an important second method of assessment, beyond the much more commonly
used self-reports. Although an extensive literature demonstrates substantial
convergent correlations between self-reported and spouse-rated emotional
adjustment, levels of adjustment evident across these 2 assessment methods are
much less commonly compared, especially among couples reporting higher levels of
marital distress. Well-documented limitations of both self-reports and spouse
ratings suggest that differences--which would not necessarily be evident in
correlations between methods--might be common and substantial, perhaps raising
complications in couple assessments and intervention. The present study compared
self-reports and spouse ratings of neuroticism and its specific components using
the NEO Personality Inventory-Revised in a sample of 301 middle-aged and older
couples. For overall neuroticism and the specific facets of anxiety, angry
hostility, and vulnerability, self-reported levels of negative emotionality were
consistently lower than the parallel ratings by spouses, most notably among
couples reporting low levels of marital adjustment. Hence, substantial
underestimates of negative emotionality obtained through self-reports as compared
to ratings by spouses (or overestimates as obtained through spouse ratings) may
be common and could complicate couple assessment and intervention.
PMID- 25844499
TI - Biomolecule-free, selective detection of o-diphenol and its derivatives with
WS2/TiO2-based photoelectrochemical platform.
AB - Herein, a novel photoelectrochemical platform with WS2/TiO2 composites as
optoelectronic materials was designed for selective detection of o-diphenol and
its derivatives without any biomolecule auxiliary. First, catechol was chosen as
a model compound for the discrimination from resorcinol and hydroquinone; then
several o-diphenol derivatives such as dopamine, caffeic acid, and catechin were
also detected by employing this proposed photoelectrochemical sensor. Finally,
the mechanism of such a selective detection has been elaborately explored. The
excellent selectivity and high sensitivity should be attributed to two aspects:
(i) chelate effect of adjacent double oxygen atoms in the o-diphenol with the
Ti(IV) surface site to form a five/six-atom ring structure, which is considered
as the key point for distinction and selective detection. (ii) This selected
WS2/TiO2 composites with proper band level between WS2 and TiO2, which could make
the photogenerated electron and hole easily separated and results in great
improvement of sensitivity. By employing such a photoelectrochemical platform,
practical samples including commercial clinic drugs and human urine samples have
been successfully performed for dopamine detection. This biomolecule-free
WS2/TiO2 based photoelectrochemical platform demonstrates excellent stability,
reproducibility, remarkably convenient, and cost-effective advantages, as well as
low detection limit (e.g., 0.32 MUmol L(-1) for dopamine). It holds great promise
to be applied for detection of o-diphenol kind species in environment and food
fields.
PMID- 25844501
TI - Bioinspired Tungsten Dithiolene Catalysts for Hydrogen Evolution: A Combined
Electrochemical, Photochemical, and Computational Study.
AB - Bis(dithiolene)tungsten complexes, W(VI)O2 (L = dithiolene)2 and W(IV)O (L =
dithiolene)2, which mimic the active site of formate dehydrogenases, have been
characterized by cyclic voltammetry and controlled potential electrolysis in
acetonitrile. They are shown to be able to catalyze the electroreduction of
protons into hydrogen in acidic organic media, with good Faradaic yields (75-95%)
and good activity (rate constants of 100 s(-1)), with relatively high
overpotentials (700 mV). They also catalyze proton reduction into hydrogen upon
visible light irradiation, in combination with [Ru(bipyridine)3](2+) as a
photosensitizer and ascorbic acid as a sacrificial electron donor. On the basis
of detailed DFT calculations, a reaction mechanism is proposed in which the
starting W(VI)O2 (L = dithiolene)2 complex acts as a precatalyst and hydrogen is
further formed from a key reduced W-hydroxo-hydride intermediate.
PMID- 25844500
TI - Nuclear Magnetic Resonance Structural Mapping Reveals Promiscuous Interactions
between Clathrin-Box Motif Sequences and the N-Terminal Domain of the Clathrin
Heavy Chain.
AB - The recruitment and organization of clathrin at endocytic sites first to form
coated pits and then clathrin-coated vesicles depend on interactions between the
clathrin N-terminal domain (TD) and multiple clathrin binding sequences on the
cargo adaptor and accessory proteins that are concentrated at such sites. Up to
four distinct protein binding sites have been proposed to be present on the
clathrin TD, with each site proposed to interact with a distinct clathrin binding
motif. However, an understanding of how such interactions contribute to clathrin
coat assembly must take into account observations that any three of these four
sites on clathrin TD can be mutationally ablated without causing loss of clathrin
mediated endocytosis. To take an unbiased approach to mapping binding sites for
clathrin-box motifs on clathrin TD, we used isothermal titration calorimetry
(ITC) and nuclear magnetic resonance spectroscopy. Our ITC experiments revealed
that a canonical clathrin-box motif peptide from the AP-2 adaptor binds to
clathrin TD with a stoichiometry of 3:1. Assignment of 90% of the total visible
amide resonances in the TROSY-HSQC spectrum of (13)C-, (2)H-, and (15)N-labeled
TD40 allowed us to map these three binding sites by analyzing the chemical shift
changes as clathrin-box motif peptides were titrated into clathrin TD. We found
that three different clathrin-box motif peptides can each simultaneously bind not
only to the previously characterized clathrin-box site but also to the W-box site
and the beta-arrestin splice loop site on a single TD. The promiscuity of these
binding sites can help explain why their mutation does not lead to larger effects
on clathrin function and suggests a mechanism by which clathrin may be
transferred between different proteins during the course of an endocytic event.
PMID- 25844502
TI - Comparison of Two Different Astragali Radix by a 1H NMR-Based Metabolomic
Approach.
AB - Astragali Radix (AR) is a commonly used herbal drug in traditional chinese
medicine and is widely used for the treatment of diabetes, cardiovascular
diseases, nephropathy, and neuropathy. The main source of AR in China is the
dried root of Astragalus membranaceus var. mongholicus (Bge.) Hsiao, and both
cultivated and wild ARs are used clinically. A systematic comparison of
cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the
clinical efficacy and safety. In this study, the chemical composition of the two
different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated)
provinces, were compared by NMR-based metabolic fingerprint coupled with
multivariate analysis. The SX-AR- and GS-AR-induced metabolic changes in the
endogenous metabolites in mice were also compared. The results showed that SX-AR
and GS-AR differed significantly not only in the primary metabolites but also in
the secondary metabolites. However, alterations among the endogenous metabolites
in the serum, lung, liver, and spleen were relatively small. This study provided
a novel and valuable method for the evaluation of the consistency and diversity
of herbal drugs, and further studies should be conducted on the difference in
polysaccharides as well as the biological effects between the two kinds of AR.
PMID- 25844503
TI - Implementation of a neonatal transcutaneous bilirubin screening programme in
rural India.
AB - BACKGROUND: Universal pre-discharge assessment of risk for neonatal
hyperbilirubinaemia is recommended by the American Academy of Pediatrics. A
common algorithm is universal transcutaneous bilirubin (TcB) screening, followed
by confirmatory total serum bilirubin (TSB) testing for results which cause
concern. There is a paucity of data on the feasibility of TcB screening in low
income settings. OBJECTIVES: To evaluate the acceptability and feasibility of
implementing universal TcB screening at a resource-limited hospital in rural
India, and to determine if it was associated with increased recognition of high
risk hyperbilirubinaemia. METHODS: In December 2012 at Vivekananda Memorial
Hospital, Karnataka, India, universal TcB screening at 24-48 hours of life was
implemented, with TSB estimated if TcB was >75th percentile for age. The
proportion of families that provided consent and the proportion of infants who
underwent TcB and TSB testing were calculated. The rates of phototherapy pre- and
post-implementation and the rate of high-risk hyperbilirubinaemia (TSB >95th
percentile for age) post-implementation among infants >= 35 weeks gestation were
determined. RESULTS: Parents of 568 of 660 (86%) eligible infants consented to
participation. All of these infants were screened with TcB. The proportion who
had TSB testing was similar in the pre- (6%) and post-implementation (7%)
periods. The rate of phototherapy was not significantly different after
implementation (2% vs 3%). Five cases of high-risk hyperbilirubinaemia were
identified post-implementation. CONCLUSIONS: The study demonstrates the
acceptability and feasibility of universal TcB screening at a resource-limited
hospital in rural India. In settings in which early post-discharge follow-up
cannot be assured, TcB can play a valuable role in identifying infants who need
evaluation.
PMID- 25844504
TI - Configurational entropy in thermoset polymers.
AB - The configurational entropy describes the atomic structure in a material and
controls several material properties. Often the configurational entropy is
determined through dielectric or calorimetric measurements where the difference
between the entropies of the crystalline state and the amorphous state is
determined. Many amorphous materials such as thermoset polymers have a high
crystallization barrier, greatly limiting the applicability of the existing
methods for determining the configurational entropy. In this work, a novel
differential scanning calorimetry (DSC) method, based on measurement of the glass
transition temperature at different heating rates, for determination of the
configurational entropy is introduced. The theory behind the method has a
universal character for amorphous materials, as it solely involves measurement of
the glass transition temperature. The temperature dependency of the
configurational entropy is determined for epoxy resins and PMMA (poly(methyl
methacrylate)) to demonstrate the versatility of the method. On the basis of the
findings of the introduced method, the influence of the degree of cross-linking
and the chemical structure of the network is discussed.
PMID- 25844505
TI - Margin Reflex Distance: Differences Based on Camera and Flash Positions.
AB - PURPOSE: To evaluate the effect of camera flash position on the measurement of
photographic margin reflex distances (MRD). METHODS: Subjects without any
ophthalmic disease were prospectively enrolled after institutional review board
approval. Clinical measurements of MRD1 and interpalpebral fissure were obtained.
Photographs were then taken with a digital single lens reflex with built-in pop
up flash (dSLR-pop), a dSLR with lens-mounted ring flash (dSLR-ring), a point-and
shoot camera, and a smartphone, each in 4 positions: with the camera upright,
rotated 90 degrees , 180 degrees , and 270 degrees . The images were analyzed
using ImageJ software to measure MRD1, interpalpebral fissure, horizontal white
to-white, and distance from nasal limbus to the corneal light reflex. RESULTS:
Thirty-two eyes of 16 subjects were included (ages 27-65). When using the dSLR
ring, point-and-shoot, and smartphone, the difference between clinical and
photographic MRD1 did not reach statistical significance. There was, however, a
statistically significant difference in the upright position with dSLR-pop (mean
difference 0.703 mm, sigma = 0.984 mm, p = 0.0008). For dSLR-pop, photographic
MRD1 in upright versus inverted position differed significantly (mean difference
0.562 mm, sigma =0.348 mm, p < 0.0001). Photographic MRD1 between dSLR-pop and
dSLR-ring showed significant difference in upright position (mean difference
0.572 mm, sigma = 0.701 mm, p = 0.0002). There were no statistically significant
differences between clinical and photographic interpalpebral fissure, and among
white-to-white and nasal limbus to light reflex measurements in any position in
all 4 cameras. CONCLUSIONS: When using photographs for measurement of MRD1,
cameras with a near-coaxial light source and aperture have values that are most
similar to clinical measurements.
PMID- 25844506
TI - Efficacy of Intravenous Mannitol in the Management of Orbital Compartment
Syndrome: A Nonhuman Primate Model.
AB - PURPOSE: To report the efficacy of intravenous mannitol in the treatment of
orbital compartment syndrome. METHODS: An experimental study was conducted on 4
nonhuman primates (8 orbits). Orbital compartment syndrome was simulated by
injecting autologous blood into both orbits of each nonhuman primate until a
pressure of 80 mm Hg was reached (time 0). After 10 minutes, nonhuman primates
were randomized to receive an infusion of either mannitol or saline, given over
15 minutes. Five minutes after the infusion was complete, lateral canthotomy and
cantholysis was performed on both orbits in isolated steps every 5 minutes.
During the study protocol, orbital and intraocular pressures were recorded every
5 minutes, with a final set of measurements at 60 minutes. The primary outcome
measures were the mean change in pressure from time 0 to 60 minutes, as well as
the mean change in pressure during the infusion period. RESULTS: There was no
statistically significant difference in the mean changes in orbital or
intraocular pressure from time 0 to 60 minutes of the protocol. However, during
the infusion period there was significantly greater decrease in both orbital and
intraocular pressure in the mannitol compared with saline group (-34.0 vs. -9.3
mm Hg for orbital pressure [p = 0.03]; -34.8 vs. -9.7 mm Hg for intraocular
pressure [p = 0.04]). CONCLUSIONS: While the definitive treatment of orbital
compartment syndrome is lateral canthotomy and cantholysis, mannitol results in a
rapid and clinically meaningful drop in orbital and intraocular pressure. The
authors believe that their data support the routine use of mannitol in orbital
compartment syndrome, especially when there is a delay in timely surgical
management.
PMID- 25844507
TI - Maxillary anterior alignment stability in Class I and Class II malocclusions
treated with or without extraction.
AB - OBJECTIVE: To compare the postretention stability of maxillary incisors alignment
in subjects with Class I and II malocclusion treated with or without extractions.
MATERIALS AND METHODS: The sample comprised 103 subjects with initial maxillary
anterior irregularity greater than 3 mm and was divided into four groups: group 1
comprised 19 patients with Class I malocclusion treated with nonextraction (mean
initial age = 13.06 years); group 2 comprised 19 patients with Class II
malocclusion treated with nonextraction (mean initial age = 12.54 years); group 3
comprised 30 patients with Class I malocclusion treated with extractions (mean
initial age = 13.16 years); group 4 comprised 35 patients with Class II
malocclusion treated with extractions (mean initial age = 12.99 years). Dental
casts were obtained at three different stages: pretreatment (T1), posttreatment
(T2), and long-term posttreatment (T3). Maxillary incisor irregularity and arch
dimensions were evaluated. Intergroup comparisons were performed by one-way
analysis of variance followed by Tukey tests. RESULTS: In the long-term
posttreatment period, relapse of maxillary crowding and arch dimensions was
similar in all groups. CONCLUSION: Changes in maxillary anterior alignment in
Class I and Class II malocclusions treated with nonextractions and with
extractions were similar in the long-term posttreatment period.
PMID- 25844508
TI - Compression and hypoxia play independent roles while having combinative effects
in the osteoclastogenesis induced by periodontal ligament cells.
AB - OBJECTIVE: To investigate the isolated and combined effects of compression and
hypoxia on the osteoclastogenesis induced by periodontal ligament cells (PDLCs).
MATERIALS AND METHODS: A periodontal ligament tissue model (PDLtm) was
established by 3-D culturing human PDLCs on a thin sheet of poly lactic-co
glycolic acid scaffold. The PDLtm was treated with hypoxia and/or compression for
6, 24, or 72 hours. After that, a real-time polymerase chain reaction was used
for gene expression analysis. The conditioned media were used for the coculture
of osteoblast and osteoclast (OC) precursors; tartrate-resistant acid phosphatase
staining was done to examine OC formation. RESULTS: Either compression or hypoxia
alone significantly up-regulated the gene expression of pro-osteoclastogenic
cytokines in the PDLtm and enhanced osteoclastogenesis in the cocultures, and the
combination of the two had significantly stronger effects than either stimulation
alone. In addition, comparing the two stimulants, we found that the
osteoclastogenic property of the PDLCs peaked earlier (at 6 hours) in the
compression group than in the hypoxia group (at 24 hours). CONCLUSIONS: Both
compressive force and hypoxia may take part in initiating osteoclastogenesis in
orthodontic tooth movement and may have combinatory effects, which could update
our concepts of the mechanisms involved in the initiation of bone resorption on
the pressure side of the tooth in question.
PMID- 25844510
TI - Lower extremity revascularization in nursing home residents: surgery as
palliation.
PMID- 25844509
TI - Objective, comparative assessment of the penetration depth of temporal-focusing
microscopy for imaging various organs.
PMID- 25844511
TI - In the Aftermath of the National Children's Study.
PMID- 25844513
TI - When domestic goes capital: Juror decision making in capital murder trials
involving domestic homicide.
AB - Prior research suggests that homicide cases involving familial offenders and
victims are subject to a "domestic discount" that reduces sentencing severity.
However, the operation of a domestic discount in regard to death penalty
sentencing has been rarely examined. The current research uses a near-population
of jury decisions in capital murder trials conducted in North Carolina from 1991
to 2009 (n = 800), and a series of logistic regression analyses to determine
whether there is (a) a direct effect between offender-victim relationship (e.g.,
domestic, friend/acquaintance, and stranger) and jury decision making, and/or (b)
whether domestic offender-victim relationship (as well as other offender-victim
relationships) moderates the effect of legal and extralegal case characteristics
on jury assessment of the death penalty. Our findings revealed no empirical
support for a "domestic discount" whereby juries are less likely to impose death
sentences in cases involving domestic homicides. However, substantial differences
in predictors of death sentencing were found across offender-victim dyads; most
notably, domestic homicide cases demonstrated the most legalistic model of jury
decisions to impose death sentences.
PMID- 25844512
TI - Oxidovanadium(IV/V) complexes as new redox mediators in dye-sensitized solar
cells: a combined experimental and theoretical study.
AB - Corrosiveness is one of the main drawbacks of using the iodide/triiodide redox
couple in dye-sensitized solar cells (DSSCs). Alternative redox couples including
transition metal complexes have been investigated where surprisingly high
efficiencies for the conversion of solar to electrical energy have been achieved.
In this paper, we examined the development of a DSSC using an electrolyte based
on square pyramidal oxidovanadium(IV/V) complexes. The oxidovanadium(IV) complex
(Ph4P)2[V(IV)O(hybeb)] was combined with its oxidized analogue
(Ph4P)[V(V)O(hybeb)] {where hybeb(4-) is the tetradentate diamidodiphenolate
ligand [1-(2-hydroxybenzamido)-2-(2-pyridinecarboxamido)benzenato}and applied as
a redox couple in the electrolyte of DSSCs. The complexes exhibit large electron
exchange and transfer rates, which are evident from electron paramagnetic
resonance spectroscopy and electrochemistry, rendering the oxidovanadium(IV/V)
compounds suitable for redox mediators in DSSCs. The very large self-exchange
rate constant offered an insight into the mechanism of the exchange reaction most
likely mediated through an outer-sphere exchange mechanism. The [V(IV)O(hybeb)](2
)/[V(V)O(hybeb)](-) redox potential and the energy of highest occupied molecular
orbital (HOMO) of the sensitizing dye N719 and the HOMO of [V(IV)O(hybeb)](2-)
were calculated by means of density functional theory electronic structure
calculation methods. The complexes were applied as a new redox mediator in DSSCs,
while the cell performance was studied in terms of the concentration of the
reduced and oxidized form of the complexes. These studies were performed with the
commercial Ru-based sensitizer N719 absorbed on a TiO2 semiconducting film in the
DSSC. Maximum energy conversion efficiencies of 2% at simulated solar light (AM
1.5; 1000 W m(-2)) with an open circuit voltage of 660 mV, a short-circuit
current of 5.2 mA cm(-2), and a fill factor of 0.58 were recorded without the
presence of any additives in the electrolyte.
PMID- 25844514
TI - Predicting recidivism among adult male child pornography offenders: Development
of the Child Pornography Offender Risk Tool (CPORT).
AB - In this study, we developed a structured risk checklist, the Child Pornography
Offender Risk Tool (CPORT), to predict any sexual recidivism among adult male
offenders with a conviction for child pornography offenses. We identified
predictors of sexual recidivism using a 5-year fixed follow-up analysis from a
police case file sample of 266 adult male child pornography offenders in the
community after their index offense. In our 5-year follow-up, 29% committed a new
offense, and 11% committed a new sexual offense, with 3% committing a new contact
sexual offense against a child and 9% committing a new child pornography offense.
The CPORT items comprised younger offender age, any prior criminal history, any
contact sexual offending, any failure on conditional release, indication of
sexual interest in child pornography material or prepubescent or pubescent
children, more boy than girl content in child pornography, and more boy than girl
content in other child depictions. The CPORT was significantly associated with
any sexual recidivism, with moderate predictive accuracy, and thus has promise in
the risk assessment of adult male child pornography offenders with further cross
validation.
PMID- 25844515
TI - Effects of victim presence and coercion in restorative justice: An experimental
paradigm.
AB - There is little experimental work examining the ways in which particular
procedural features of restorative justice impact offenders. This research
describes a new experimental paradigm designed to advance knowledge about causal
relationships in restorative justice settings. Apologizing is a core component of
restorative procedures, and can result in beneficial outcomes, but previous
research suggests that coercion to apologize and the absence of victims in
restorative procedures may negatively impact these outcomes. The experimental
procedure elicited confessions and apologies for a transgression from
participants (N = 101) in a deceptive paradigm. We manipulated coercion (coerced,
not coerced) and victim presence (direct, surrogate, ambiguous) to test their
effects on offenders' subjective experiences of offering an apology, as well as
their effects on the quality of offenders' apologies. Findings indicated that the
victim presence and coercion manipulations significantly impacted some of the
subjective perceptions of apologizers, including perceptions of accountability
and transgression finality. In addition, independent raters evaluated the degree
to which the transgressor's apologies conveyed remorse, acceptance of guilt, and
potential for dispute resolution. Victim presence and coercion consistently
affected the ability of transgressors to convey high quality apologies.
Implications for future research and restorative procedures are discussed.
PMID- 25844516
TI - Using reality monitoring to improve deception detection in the context of the
cognitive interview for suspects.
AB - Research has found that deception detection accuracy in the context of suspect
interrogation hovers around chance levels. Geiselman (2012) adapted the cognitive
interview (typically used for witnesses) for use with suspects (CIS) and found
that judgments of deception were more accurate than previous interrogation
techniques. The current study attempted to use the CIS to improve deception
detection with Reality Monitoring (RM: Vrij et al., 2008), which has already been
validated in the context of witness statements. One hundred sixty-six
undergraduate students were randomly assigned to 2 conditions. In the Truthful
condition, participants played a game with a confederate, whereas in the
Deceptive condition, participants rehearsed (but did not experience) a synopsis
of the game scenario. Participants in the Deceptive condition were also
instructed to steal $10 from a confederate's wallet. In both conditions, $10 was
purported to be missing and a researcher blind to condition conducted a CIS.
Statement veracity was coded using 6 of the RM criteria advanced by Vrij et al.
(frequency of visual, auditory, spatial, temporal, cognitive, and affective
details). According to results from a MANOVA, truthful and deceptive statements
differed significantly on all RM criteria, with the exception of affective
details, validating the importance for evaluation of statement veracity (p <=
.01). Further, a binary logistic regression found that combining the RM criteria
together correctly classified 86.6% of statements, chi(2)(6) = 114.4, p < .001,
with excellent sensitivity and specificity (.899 and .833, respectively). As
well, Visual, Auditory, and Cognitive details uniquely predicted condition.
Findings support using RM criteria to detect deception in interviews conducted
with the CIS.
PMID- 25844517
TI - Interviewing strategically to elicit admissions from guilty suspects.
AB - In this article we introduce a novel interviewing tactic to elicit admissions
from guilty suspects. By influencing the suspects' perception of the amount of
evidence the interviewer holds against them, we aimed to shift the suspects'
counterinterrogation strategies from less to more forthcoming. The proposed
tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence
(SUE) framework and aims to affect the suspects' perception by confronting them
with statement-evidence inconsistencies. Participants (N = 90) were asked to
perform several mock criminal tasks before being interviewed using 1 of 3
interview techniques: (a) SUE-Confrontation, (b) Early Disclosure of Evidence, or
(c) No Disclosure of Evidence. As predicted, the SUE-Confrontation interview
generated more statement-evidence inconsistencies from suspects than the Early
Disclosure interview. Importantly, suspects in the SUE-Confrontation condition
(vs. Early and No disclosure conditions) admitted more self-incriminating
information and also perceived the interviewer to have had more information about
the critical phase of the crime (the phase where the interviewer lacked
evidence). The findings show the adaptability of the SUE-technique and how it may
be used as a tool for eliciting admissions.
PMID- 25844519
TI - Use of smartphone cameras for simplified and cost-effective video recording of
microvascular techniques.
PMID- 25844520
TI - Severe traumatic facial injury: avatars and thermographic damage evaluation.
PMID- 25844521
TI - Reply: Modified Transconjunctival Lower Lid Approach for Orbital Fractures in
East Asian Patients: The Lateral Paracanthal Incision Revisited.
PMID- 25844522
TI - Ultrafast imaging of surface plasmons propagating on a gold surface.
AB - We record time-resolved nonlinear photoemission electron microscopy (tr-PEEM)
images of propagating surface plasmons (PSPs) launched from a lithographically
patterned rectangular trench on a flat gold surface. Our tr-PEEM scheme involves
a pair of identical, spatially separated, and interferometrically locked
femtosecond laser pulses. Power-dependent PEEM images provide experimental
evidence for a sequential coherent nonlinear photoemission process, in which one
laser source launches a PSP through a linear interaction, and the second
subsequently probes the PSP via two-photon photoemission. The recorded time
resolved movies of a PSP allow us to directly measure various properties of the
surface-bound wave packet, including its carrier wavelength (783 nm) and group
velocity (0.95c). In addition, tr-PEEM images reveal that the launched PSP may be
detected at least 250 MUm away from the coupling trench structure.
PMID- 25844518
TI - Nanoscale strategies: treatment for peripheral vascular disease and critical limb
ischemia.
AB - Peripheral vascular disease (PVD) is one of the most prevalent vascular diseases
in the U.S. afflicting an estimated 8 million people. Obstruction of peripheral
arteries leads to insufficient nutrients and oxygen supply to extremities, which,
if not treated properly, can potentially give rise to a severe condition called
critical limb ischemia (CLI). CLI is associated with extremely high morbidities
and mortalities. Conventional treatments such as angioplasty, atherectomy, stent
implantation and bypass surgery have achieved some success in treating localized
macrovascular disease but are limited by their invasiveness. An emerging
alternative is the use of growth factor (delivered as genes or proteins) and cell
therapy for PVD treatment. By delivering growth factors or cells to the ischemic
tissue, one can stimulate the regeneration of functional vasculature network
locally, re-perfuse the ischemic tissue, and thus salvage the limb. Here we
review recent advance in nanomaterials, and discuss how their application can
improve and facilitate growth factor or cell therapies. Specifically,
nanoparticles (NPs) can serve as drug carrier and target to ischemic tissues and
achieve localized and sustained release of pro-angiogenic proteins. As nonviral
vectors, NPs can greatly enhance the transfection of target cells with pro
angiogenic genes with relatively fewer safety concern. Further, NPs may also be
used in combination with cell therapy to enhance cell retention, cell survival
and secretion of angiogenic factors. Lastly, nano/micro fibrous vascular grafts
can be engineered to better mimic the structure and composition of native
vessels, and hopefully overcome many complications/limitations associated with
conventional synthetic grafts.
PMID- 25844524
TI - Nine new phosphorene polymorphs with non-honeycomb structures: a much extended
family.
AB - We predict a new class of monolayer phosphorus allotropes, namely, epsilon-P,
zeta-P, eta-P, and theta-P. Distinctly different from the monolayer alpha-P
(black) and previously predicted beta-P (Phys. Rev. Lett. 2014, 112, 176802),
gamma-P, and delta-P (Phys. Rev. Lett. 2014, 113, 046804) with buckled honeycomb
lattice, the new allotropes are composed of P4 square or P5 pentagon units that
favor tricoordination for P atoms. The new four polymorphs, together with five
additional hybrid polymorphs, greatly enrich the phosphorene structures, and
their stabilities are confirmed by first-principles calculations. In particular,
the theta-P is shown to be equally stable as the alpha-P (black) and more stable
than all previously reported phosphorene polymorphs. Prediction of nonvolatile
ferroelastic switching and structural transformation among different polymorphs
under strains points out their potential applications via strain engineering.
PMID- 25844523
TI - Functional outcomes after lower extremity revascularization in nursing home
residents: a national cohort study.
AB - IMPORTANCE: Lower extremity revascularization often seeks to allow patients with
peripheral arterial disease to maintain the ability to walk, a key aspect of
functional independence. Surgical outcomes in patients with high levels of
functional dependence are poorly understood. OBJECTIVE: To determine functional
status trajectories, changes in ambulatory status, and survival after lower
extremity revascularization in nursing home residents. DESIGN: Using full
Medicare claims data for 2005 to 2009, we identified nursing home residents who
underwent lower extremity revascularization. With the Minimum Data Set for
Nursing Homes activities of daily living summary score, we examined changes in
their ambulatory and functional status after surgery. We identified patient and
surgery characteristics associated with a composite measure of clinical and
functional failure-death or nonambulatory status 1 year after surgery. SETTING:
All nursing homes in the United States participating in Medicare or Medicaid.
PARTICIPANTS: Nursing home residents who underwent lower extremity
revascularization. MAIN OUTCOMES AND MEASURES: Functional status, ambulatory
status, and death. RESULTS: During the study period, 10,784 long-term nursing
home residents underwent lower extremity revascularization. Prior to surgery, 75%
of the residents were not walking; 40% had experienced functional decline. One
year after surgery, 51% of patients had died, 28% were nonambulatory, and 32% had
sustained functional decline. Among 1672 residents who were ambulatory before
surgery, 63% had died or were nonambulatory at 1 year; among 7188 who were
nonambulatory, 89% had died or were nonambulatory. After multivariate adjustment,
factors independently associated with death or nonambulatory status were 80 years
or older (adjusted hazard ratio [AHR], 1.28; 95% CI, 1.16-1.40), cognitive
impairment (AHR, 1.23; 95% CI, 1.18-1.29), congestive heart failure (AHR, 1.16;
95% CI, 1.11-1.22), renal failure (AHR, 1.09; 95% CI, 1.04-1.14), emergent
surgery (AHR, 1.29; 95% CI, 1.23-1.35), nonambulatory status before surgery (AHR,
1.88; 95% CI, 1.78-1.99), and decline in activities of daily living before
surgery (AHR, 1.23; 95% CI, 1.18-1.28). CONCLUSIONS AND RELEVANCE: Of nursing
home residents in the United States who undergo lower extremity
revascularization, few are alive and ambulatory 1 year after surgery. Most who
were still alive had gained little, if any, function.
PMID- 25844525
TI - Untangling the etiology of ascites.
AB - BACKGROUND: Amyloidosis is a systemic disease known to affect a vast range of
organs, including the liver, heart, and kidney. When infiltrating the liver,
amyloidosis typically does not present with cirrhosis. Typical presentation
includes hepatomegaly with some mild laboratory abnormalities. CASE REPORT: A 72
year-old man presented with a 2-week history of worsening abdominal, scrotal, and
extremity swelling. He endorsed melanotic stools and intermittent dizziness with
a 10-pound weight gain. Vitals revealed a blood pressure of 82/57 mmHg and a
pulse of 83 beats/min with positive orthostatic changes. Mild bibasilar crackles
were noted. His abdomen was moderately distended with a fluid wave present, but
no hepatosplenomegaly was noted. He displayed anasarca with significant extremity
and scrotal edema, but no jaundice, telangiectasias, or other stigmata of chronic
liver disease were present. Liver function tests demonstrated a total bilirubin
of 1.5 mg/dL (normal value: 0.2-1.2 mg/dL), AST 111 IU/L (normal value 5-34
IU/L), ALT 51 IU/L (normal value 5-55 IU/L), and GGT 583 U/L (12-64 U/L).
Alkaline phosphatase was 645 U/L (40-150 U/L). Analysis of peritoneal fluid was
consistent with portal hypertension due to liver disease. Given an atypical
presentation of cirrhosis with unclear etiology, a biopsy was performed and
revealed amyloid deposition. CONCLUSIONS: Liver disease can be due to various
etiologies, many of which can present ambiguously. Although the most typical
etiologies have been well defined, we present a case of an atypical presentation
of hepatic amyloidosis discovered in a patient with ascites and without typical
hepatomegaly.
PMID- 25844526
TI - Preference for cute infants does not depend on their ethnicity or species:
evidence from hypothetical adoption and donation paradigms.
AB - Results of previous work suggest a preference of adult observers for cute
compared to less cute infants. In Study 1 we investigated whether the preference
for cute infants depends on the ethnicity and species of the infant. We
simultaneously presented two faces (one cute and one less cute) and asked
Caucasian participants to choose the infant to whom they would rather give a toy
(Task 1) and which infant they would rather adopt (Task 2). The infants were
Caucasian or African human babies or dog puppies. For all face categories and in
both tasks we found a strong preference for cute infants. A possible reason for
preferring cute infants may be that cute infants look healthier than less cute
infants. To investigate whether cuteness is associated with the assessment of
health we conducted Study 2. Faces of Caucasian and African infants and dog
puppies were rated for cuteness and health. The findings revealed a significant
relationship between health and cuteness evaluation across all stimuli. We
suggest that one reason why cute infants are preferred might be because they are
perceived as being healthier.
PMID- 25844527
TI - Practice Guidance for Buprenorphine for the Treatment of Opioid Use Disorders:
Results of an Expert Panel Process.
AB - BACKGROUND: Although the number of physicians credentialed to prescribe
buprenorphine has increased over time, many credentialed physicians may be
reluctant to treat individuals with opioid use disorders due to discomfort with
prescribing buprenorphine. Although prescribing physicians are required to
complete a training course, many have questions about buprenorphine and treatment
guidelines have not been updated to reflect clinical experience in recent years.
We report on an expert panel process to update and expand buprenorphine
guidelines. METHODS: We identified candidate guidelines through expert opinion
and a review of the literature and used a modified RAND/UCLA Appropriateness
Method to assess the validity of the candidate guidelines. An expert panel
completed 2 rounds of rating, with a meeting to discuss the guidelines between
the first and second ratings. RESULTS: Through the rating process, expert panel
members rated 90 candidate guideline statements across 8 domains, including
candidacy for buprenorphine treatment, dosing of buprenorphine, psychosocial
counseling, and treatment of co-occurring depression and anxiety. A total of 65
guideline statements (72%) were rated as valid. Expert panel members had
agreement in some areas, such as the treatment of co-occurring mental health
problems, but disagreement in others, including the appropriate dosing of
buprenorphine given patient complexities. CONCLUSIONS: Through an expert panel
process, we developed an updated and expanded set of buprenorphine treatment
guidelines; this additional guidance may increase credentialed physicians'
comfort with prescribing buprenorphine to patients with opioid use disorders.
Future efforts should focus on appropriate dosing guidance and ensuring that
guidelines can be adapted to a variety of practice settings.
PMID- 25844528
TI - Substrate-Controlled Stereochemistry in Natural Product Biosynthesis.
AB - Enzymes are generally believed to be highly regio- and stereoselective catalysts
that strictly control the reaction coordinates and dominate the final catalytic
outcomes. However, recent studies have started to suggest that substrates
sometimes play key roles in determining the product selectivity in enzyme
catalysis. Here, we highlight several enzymatic reactions in which the
stereoselectivity is, at least in large part, governed by the intrinsic
properties of the substrate rather than by characteristics of the enzyme. These
reactions are involved in the biosynthesis of different classes of natural
products, including lanthipeptides, sactipeptides, and polyketides. Understanding
the mechanism of substrate-controlled stereospecificity may not only expand our
knowledge of enzyme catalysis and enzyme evolution but also guide bioengineering
efforts to produce novel valuable products.
PMID- 25844529
TI - TLR9 2848 GA heterozygotic status possibly predisposes fetuses and newborns to
congenital infection with human cytomegalovirus.
AB - BACKGROUND: Some single nucleotide polymorphisms (SNP), located in Toll-like
receptor (TLR) genes, were reported to be associated with human cytomegalovirus
(HCMV) infections. The study was aimed to assess the correlation of SNPs at TLR4
and TLR9 genes with the occurrence of congenital cytomegaly, based on available
samples. METHODS: Reported case-control study included both HCMV infected and non
infected fetuses and newborns. The specimens were classified to the molecular
analyses, based on serological features of the recent infection and HCMV DNAemia
in body fluids. TLR SNPs were studied, using multiplex nested PCR-RFLP assay, and
determined genotypes were confirmed by sequencing. Hardy-Weinberg equilibrium was
assessed for the identified genotypes. The linkage disequilibrium was also
estimated for TLR4 SNPs. A relationship between the status of TLR genotypes and
congenital cytomegaly development was estimated, using a logistic regression
model. RESULTS: Hardy Weinberg equilibrium was observed for almost all SNPs, both
infected and non-infected patients, with exception of TLR4 896 A>G polymorphism
in the control group (P<=0.050). TLR4 896 A>G and 1196 C>T SNPs were found in
linkage disequilibrium in both study groups (P<=0.050). The CC genotype at TLR4
1196 SNP and the GA variant at TLR9 2848 G>A SNP were significantly associated
with HCMV infection (P<=0.050). The risk of congenital cytomegaly was higher in
heterozygotes at TLR9 SNP than in the carriers of other genotypic variants at the
reported locus (OR 4.81; P<=0.050). The GC haplotype at TLR4 SNPs and GCA
variants at TLR4 and TLR9 SNPs were significantly associated with HCMV infection
(P<=0.0001). The ACA variants were more frequent among fetuses and neonates with
symptomatic, rather than asymptomatic cytomegaly (P<=0.0001). CONCLUSIONS: TLR4
and TLR9 polymorphisms may contribute to the development of congenital infection
with HCMV in fetuses and neonates. The TLR9 2848 GA heterozygotic status possibly
predisposes to HCMV infection, increasing the risk of congenital cytomegaly
development.
PMID- 25844530
TI - Endurance training alters basal erythrocyte MCT-1 contents and affects the
lactate distribution between plasma and red blood cells in T2DM men following
maximal exercise.
AB - Chronic elevated lactate levels are associated with insulin resistance in
patients with type 2 diabetes mellitus (T2DM). Furthermore, lactacidosis plays a
role in limiting physical performance. Erythrocytes, which take up lactate via
monocarboxylate transporter (MCT) proteins, may help transport lactate within the
blood from lactate-producing to lactate-consuming organs. This study investigates
whether cycling endurance training (3 times/week for 3 months) alters the basal
erythrocyte content of MCT-1, and whether it affects lactate distribution
kinetics in the blood of T2DM men (n = 10, years = 61 +/- 9, body mass index = 31
+/- 3 kg/m(2)) following maximal exercise (WHO step-incremental cycle ergometer
test). Immunohistochemical staining indicated that basal erythrocyte contents of
MCT-1 protein were up-regulated (+90%, P = 0.011) post-training. Erythrocyte and
plasma lactate increased from before acute exercise (= resting values) to
physical exhaustion pre- as well as post-training (pre-training: +309%, P =
0.004; +360%, P < 0.001; post-training: +318%, P = 0.008; +300%, P < 0.001), and
did not significantly decrease during 5 min recovery. The lactate ratio
(erythrocytes:plasma) remained unchanged after acute exercise pre-training, but
was significantly increased after 5 min recovery post-training (compared with the
resting value) (+22%, P = 0.022). The results suggest an increased time-delayed
influx of lactate into erythrocytes following an acute bout of exercise in
endurance-trained diabetic men.
PMID- 25844532
TI - Using estimated factor scores from a bifactor analysis to examine the unique
effects of the latent variables measured by the WAIS-IV on academic achievement.
AB - This study used estimated factor scores from a bifactor analysis of the Wechsler
Adult Intelligence Scale-Fourth Edition (WAIS-IV) to examine the unique effects
of its latent variables on academic achievement. In doing so, we addressed the
potential limitation of multicollinearity in previous studies of the incremental
validity of the WAIS-IV. First, factor scores representing psychometric g and 4
group factors representing the WAIS-IV index scales were computed from a bifactor
model. Subtest and composite scores for the Wechsler Individual Achievement Test
Third Edition (WIAT-II) were then predicted from these estimated factor scores in
simultaneous multiple regression. Results of this study only partially replicated
the findings of previous research on the incremental validity of scores that can
be derived from performance on the WAIS-IV. Although we found that psychometric g
is the most important underlying construct measured by the WAIS-IV for the
prediction of academic achievement in general, results indicated that the unique
effect of Verbal Comprehension is also important for predicting achievement in
reading, spelling, and oral communication skills. Based on these results,
measures of both psychometric g and Verbal Comprehension could be cautiously
interpreted when considering high school students' performance in these areas of
achievement.
PMID- 25844531
TI - Intrinsic patterns of coupling between correlation and amplitude of low-frequency
fMRI fluctuations are disrupted in degenerative dementia mainly due to functional
disconnection.
AB - Low frequency fluctuations (LFFs) of the BOLD signal are a major discovery in the
study of the resting brain with functional magnetic resonance imaging (fMRI). Two
fMRI-based measures, functional connectivity (FC), a measure of signal
synchronicity, and the amplitude of LFFs (ALFF), a measure of signal periodicity,
have been proved to be sensitive to changes induced by several neurological
diseases, including degenerative dementia. In spite of the increasing use of
these measures, whether and how they are related to each other remains to be
elucidated. In this work we used voxel-wise FC and ALFF computed in different
frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; and full-band:
0.01-0.073 Hz), in order to assess their relationship in healthy elderly as well
as the relevant changes induced by Alzheimer's Disease (AD) and Mild Cognitive
Impairment (MCI). We found that in healthy elderly subjects FC and ALFF are
positively correlated in anterior and posterior cingulate cortex (full-band, slow
4 and slow-5), temporal cortex (full-band and slow-5), and in a set of
subcortical regions (full-band and slow-4). These correlation patterns between FC
and ALFF were absent in either AD or MCI patients. Notably, the loss of
correlation between FC and ALFF in the AD group was primarily due to changes in
FC rather than in ALFF. Our results indicate that degenerative dementia is
characterized by a loss of global connection rather than by a decrease of
fluctuation amplitude.
PMID- 25844533
TI - Development and initial validation of the Child Disgust Scale.
AB - Although disgust sensitivity (DS) has been implicated in the development of
anxiety disorders in children, the absence of a measure of DS specifically for
children has not allowed for an adequate test of this claim. To fill this
important gap in the literature, this investigation presents a series of studies
on the development and examination of the psychometric properties (including
reliability, validity, and factor structure) of scores on a newly developed Child
Disgust Scale (CDS). Exploratory factor analysis in Study 1 (N = 1,500) found
that a bifactor model, which allows for a "g" DS factor in addition to 2 distinct
factors of Disgust Avoidance and Disgust Affect, was the best fit for the data.
Study 2 (N = 573) confirmed a two-factor bifactor model above and beyond a 1
factor model that controlled for method effects due to reverse-worded items.
Results from Study 3 (N = 50) provided support for convergent and discriminant
validity such that scores on the CDS were significantly correlated with measures
of anxiety and fear, but not depression. Finally, Study 4 (N = 86) found that the
CDS differentiated children with a diagnosis of specific phobia (n = 43) from a
matched nonclinical community sample of children (n = 43), such that those with a
specific phobia reported greater DS compared with controls. Results from these
studies suggest that the CDS is a developmentally appropriate measure with good
psychometric properties that can aid research on the role of disgust sensitivity
in anxiety-related disorders in children.
PMID- 25844535
TI - Electrokinetic control of bacterial deposition and transport.
AB - Microbial biofilms can cause severe problems in technical installations where
they may give rise to microbially influenced corrosion and clogging of filters
and membranes or even threaten human health, e.g. when they infest water
treatment processes. There is, hence, high interest in methods to prevent
microbial adhesion as the initial step of biofilm formation. In environmental
technology it might be desired to enhance bacterial transport through porous
matrices. This motivated us to test the hypothesis that the attractive
interaction energy allowing cells to adhere can be counteracted and overcome by
the shear force induced by electroosmotic flow (EOF, i.e. the water flow over
surfaces exposed to a weak direct current (DC) electric field). Applying EOF of
varying strengths we quantified the deposition of Pseudomonas fluorescens Lp6a in
columns containing glass collectors and on a quartz crystal microbalance. We
found that the presence of DC reduced the efficiency of initial adhesion and
bacterial surface coverage by >85%. A model is presented which quantitatively
explains the reduction of bacterial adhesion based on the extended Derjaguin,
Landau, Verwey, and Overbeek (XDLVO) theory of colloid stability and the EOF
induced shear forces acting on a bacterium. We propose that DC fields may be used
to electrokinetically regulate the interaction of bacteria with surfaces in order
to delay initial adhesion and biofilm formation in technical installations or to
enhance bacterial transport in environmental matrices.
PMID- 25844534
TI - Testing whether the DSM-5 personality disorder trait model can be measured with a
reduced set of items: An item response theory investigation of the Personality
Inventory for DSM-5.
AB - The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) includes an alternative model of personality disorders (PDs) in Section
III, consisting in part of a pathological personality trait model. To date, the
220-item Personality Inventory for DSM-5 (PID-5; Krueger, Derringer, Markon,
Watson, & Skodol, 2012) is the only extant self-report instrument explicitly
developed to measure this pathological trait model. The present study used item
response theory-based analyses in a large sample (n = 1,417) to investigate
whether a reduced set of 100 items could be identified from the PID-5 that could
measure the 25 traits and 5 domains. This reduced set of PID-5 items was then
tested in a community sample of adults currently receiving psychological
treatment (n = 109). Across a wide range of criterion variables including NEO PI
R domains and facets, DSM-5 Section II PD scores, and externalizing and
internalizing outcomes, the correlational profiles of the original and reduced
versions of the PID-5 were nearly identical (rICC = .995). These results provide
strong support for the hypothesis that an abbreviated set of PID-5 items can be
used to reliably, validly, and efficiently assess these personality disorder
traits. The ability to assess the DSM-5 Section III traits using only 100 items
has important implications in that it suggests these traits could still be
measured in settings in which assessment-related resources (e.g., time,
compensation) are limited.
PMID- 25844536
TI - Wastewater analysis to monitor spatial and temporal patterns of use of two
synthetic recreational drugs, ketamine and mephedrone, in Italy.
AB - Wastewater analysis was applied in a four-year monitoring study to assess
temporal and spatial patterns of ketamine and mephedrone use in the general
population in Italy. Composite raw wastewater samples were collected from sewage
treatment plants (STPs) in 17 cities. Target analytes were measured using a
validated method based on solid phase extraction and liquid chromatography
coupled to tandem mass spectrometry analysis. Mass loads were use to assess
ketamine and mephedrone use and were normalized to the population served by the
plants. Ketamine was detected in wastewater in all except one (Palermo) of the
cities investigated, while mephedrone was detected only in Bologna and Florence.
Ketamine mass loads progressively increased from 2010 to 2013, and in Milan rose
from 1 to 1.5 g/day in 2008-2010 to 3.4-3.6 g/day in 2013-2014. Mass loads were
higher in north and central Italy than in the south, and in larger rather than
small cities. Wastewater analysis was suitable to provide objective and up-to
date information on the use of ketamine in Italy, to identify ketamine spatial
and temporal changes, and to confirm the low use of mephedrone. These results can
complement information from population surveys which often provide only scant and
incomplete figures for these substances.
PMID- 25844537
TI - Hybridized electromagnetic-triboelectric nanogenerator for scavenging air-flow
energy to sustainably power temperature sensors.
AB - We report a hybridized nanogenerator with dimensions of 6.7 cm * 4.5 cm * 2 cm
and a weight of 42.3 g that consists of two triboelectric nanogenerators (TENGs)
and two electromagnetic generators (EMGs) for scavenging air-flow energy. Under
an air-flow speed of about 18 m/s, the hybridized nanogenerator can deliver
largest output powers of 3.5 mW for one TENG (in correspondence of power per unit
mass/volume: 8.8 mW/g and 14.6 kW/m(3)) at a loading resistance of 3 MOmega and
1.8 mW for one EMG (in correspondence of power per unit mass/volume: 0.3 mW/g and
0.4 kW/m(3)) at a loading resistance of 2 kOmega, respectively. The hybridized
nanogenerator can be utilized to charge a capacitor of 3300 MUF to sustainably
power four temperature sensors for realizing self-powered temperature sensor
networks. Moreover, a wireless temperature sensor driven by a hybridized
nanogenerator charged Li-ion battery can work well to send the temperature data
to a receiver/computer at a distance of 1.5 m. This work takes a significant step
toward air-flow energy harvesting and its potential applications in self-powered
wireless sensor networks.
PMID- 25844538
TI - Building allied health workforce capacity: a strategic approach to workforce
innovation.
AB - OBJECTIVE: The aim of the present study was to identify areas where allied health
assistants (AHAs) are not working to their full scope of practice in order to
improve the effectiveness of the allied health workforce. METHODS: Qualitative
data collected via focus groups identified suitable AHA tasks and a quantitative
survey with allied health professionals (AHPs) measured the magnitude of work the
current AHP workforce spends undertaking these tasks. RESULTS: Quantification
survey results indicate that Victoria's AHP workforce spends up to 17% of time
undertaking tasks that could be delegated to an AHA who has relevant training and
adequate supervision. Over half this time is spent on clinical tasks.
CONCLUSIONS: The skills of AHAs are not being optimally utilised. Significant
opportunity exists to reform the current allied health workforce. Such reform
should result in increased capacity of the workforce to meet future demands.
PMID- 25844541
TI - Evaluating the Risks of High Altitude Travel in Chronic Liver Disease Patients.
AB - Luks, Andrew M., and Erik R. Swenson. Clinician's Corner: Evaluating the risks of
high altitude travel in chronic liver disease patients. High Alt Med Biol 16:80
88, 2015.--With improvements in the quality of health care, people with chronic
medical conditions are experiencing better quality of life and increasingly
participating in a wider array of activities, including travel to high altitude.
Whenever people with chronic diseases travel to this environment, it is important
to consider whether the physiologic responses to hypobaric hypoxia will interact
with the underlying medical condition such that the risk of acute altitude
illness is increased or the medical condition itself may worsen. This review
considers these questions as they pertain to patients with chronic liver disease.
While the limited available evidence suggests there is no evidence of liver
injury or dysfunction in normal individuals traveling as high as 5000 m, there is
reason to suspect that two groups of cirrhosis patients are at increased risk for
problems, hepatopulmonary syndrome patients, who are at risk for severe hypoxemia
following ascent, and portopulmonary hypertension patients who may be at risk for
high altitude pulmonary edema and acute right ventricular dysfunction. While
liver transplant patients may tolerate high altitude exposure without difficulty,
no information is available regarding the risks of long-term residence at
altitude with chronic liver disease. All travelers with cirrhosis require careful
pre-travel evaluation to identify conditions that might predispose to problems at
altitude and develop risk mitigation strategies for these issues. Patients also
require detailed counseling about recognition, prevention, and treatment of acute
altitude illness and may require different medication regimens to prevent or
treat altitude illness than used in healthy individuals.
PMID- 25844540
TI - Fully automated fluorescent in situ hybridization (FISH) staining and digital
analysis of HER2 in breast cancer: a validation study.
AB - HER2 assessment is routinely used to select patients with invasive breast cancer
that might benefit from HER2-targeted therapy. The aim of this study was to
validate a fully automated in situ hybridization (ISH) procedure that combines
the automated Leica HER2 fluorescent ISH system for Bond with supervised
automated analysis with the Visia imaging D-Sight digital imaging platform. HER2
assessment was performed on 328 formalin-fixed/paraffin-embedded invasive breast
cancer tumors on tissue microarrays (TMA) and 100 (50 selected IHC 2+ and 50
random IHC scores) full-sized slides of resections/biopsies obtained for
diagnostic purposes previously. For digital analysis slides were pre-screened at
20x and 100x magnification for all fluorescent signals and supervised-automated
scoring was performed on at least two pictures (in total at least 20 nuclei were
counted) with the D-Sight HER2 FISH analysis module by two observers
independently. Results were compared to data obtained previously with the manual
Abbott FISH test. The overall agreement with Abbott FISH data among TMA samples
and 50 selected IHC 2+ cases was 98.8% (kappa = 0.94) and 93.8% (kappa = 0.88),
respectively. The results of 50 additionally tested unselected IHC cases were
concordant with previously obtained IHC and/or FISH data. The combination of the
Leica FISH system with the D-Sight digital imaging platform is a feasible method
for HER2 assessment in routine clinical practice for patients with invasive
breast cancer.
PMID- 25844539
TI - Transcriptional profile of Mycobacterium tuberculosis replicating in type II
alveolar epithelial cells.
AB - Mycobacterium tuberculosis (M. tb) infection is initiated by the few bacilli
inhaled into the alveolus. Studies in lungs of aerosol-infected mice provided
evidence for extensive replication of M. tb in non-migrating, non-antigen
presenting cells in the alveoli during the first 2-3 weeks post-infection.
Alveoli are lined by type II and type I alveolar epithelial cells (AEC) which
outnumber alveolar macrophages by several hundred-fold. M. tb DNA and viable M.
tb have been demonstrated in AEC and other non-macrophage cells of the kidney,
liver, and spleen in autopsied tissues from latently-infected subjects from TB
endemic regions indicating systemic bacterial dissemination during primary
infection. M. tb have also been demonstrated to replicate rapidly in A549 cells
(type II AEC line) and acquire increased invasiveness for endothelial cells.
Together, these results suggest that AEC could provide an important niche for
bacterial expansion and development of a phenotype that promotes dissemination
during primary infection. In the current studies, we have compared the
transcriptional profile of M. tb replicating intracellularly in A549 cells to
that of M. tb replicating in laboratory broth, by microarray analysis. Genes
significantly upregulated during intracellular residence were consistent with an
active, replicative, metabolic, and aerobic state, as were genes for tryptophan
synthesis and for increased virulence (ESAT-6, and ESAT-6-like genes, esxH, esxJ,
esxK, esxP, and esxW). In contrast, significant downregulation of the DevR (DosR)
regulon and several hypoxia-induced genes was observed. Stress response genes
were either not differentially expressed or were downregulated with the exception
of the heat shock response and those induced by low pH. The intra-type II AEC M.
tb transcriptome strongly suggests that AEC could provide a safe haven in which
M. tb can expand dramatically and disseminate from the lung prior to the
elicitation of adaptive immune responses.
PMID- 25844542
TI - PAH Measurements in Air in the Athabasca Oil Sands Region.
AB - Polycyclic aromatic hydrocarbon (PAH) measurements were conducted by Wood Buffalo
Environmental Association (WBEA) at four community ambient Air quality Monitoring
Stations (AMS) in the Athabasca Oil Sands Region (AOSR) in Northeastern Alberta,
Canada. The 2012 and 2013 mean concentrations of a subset of the 22 PAH species
were 9.5, 8.4, 8.8, and 32 ng m(-3) at AMS 1 (Fort McKay), AMS 6 (residential
Fort McMurray), AMS 7 (downtown Fort McMurray), and AMS 14 (Anzac), respectively.
The average PAH concentrations in Fort McKay and Fort McMurray were in the range
of rural and semirural areas, but peak values reflect an industrial emission
influence. At these stations, PAHs were generally associated with NO, NO2, PM2.5,
and SO2, indicating the emissions were from the combustion sources such as
industrial stacks, vehicles, residential heating, and forest fires, whereas the
PAH concentrations at AMS 14 (~35 km south of Fort McMurray) were more
characteristic of urban areas with a unique pattern: eight of the lower molecular
weight PAHs exhibited strong seasonality with higher levels during the warmer
months. Enthalpies calculated from Clausius-Clapeyron plots for these eight PAHs
suggest that atmospheric emissions were dominated by temperature-dependent
processes such as volatilization at warm temperatures. These findings point to
the potential importance of localized water-air and/or surface-air transfer on
observed PAH concentrations in air.
PMID- 25844544
TI - Non-aqueous Isorefractive Pickering Emulsions.
AB - Non-aqueous Pickering emulsions of 16-240 MUm diameter have been prepared using
diblock copolymer worms with ethylene glycol as the droplet phase and an n-alkane
as the continuous phase. Initial studies using n-dodecane resulted in stable
emulsions that were significantly less turbid than conventional water-in-oil
emulsions. This is attributed to the rather similar refractive indices of the
latter two phases. By utilizing n-tetradecane as an alternative oil that almost
precisely matches the refractive index of ethylene glycol, almost isorefractive
ethylene glycol-in-n-tetradecane Pickering emulsions can be prepared. The droplet
diameter and transparency of such emulsions can be systematically varied by
adjusting the worm copolymer concentration.
PMID- 25844543
TI - Synthesis of a C(1)-C(23) fragment for spirastrellolide E: development of a
mechanistic rationale for spiroketalization.
AB - Synthetic analysis of spirastrellolide E envisioned to entail a cross-metathesis
union of the northern and southern hemispheres followed by a Sharpless
epoxidation/methylation sequence to achieve the C(22,23) stereogenicity leads to
the design of a C(1)-C(23) advanced southern hemisphere exploiting a gold
catalyzed directed spiroketalization as a key step. Stereochemical analysis of
this strategic transformation provides insight on the impact of the directing
group carbinol stereogenicity on the reaction efficiency and, in turn, permits
the conversion of the minor isomer of the spiroketal precursor to the requisite
congener for successful spiroketalization.
PMID- 25844545
TI - p16INK4a immunohistochemical and histopathologic study of Pap test cases
interpreted as HSIL without CIN2-3 identification in subsequent cervical
specimens.
AB - Tissue biopsy following a pap test diagnosis of high grade squamous
intraepithelial lesion (HSIL) sometimes fails to confirm the presence of a
corresponding high grade cervical intraepithelial lesion (CIN 2-3), leading to
confusion as to how best to manage the patient. It has been shown that these
patients are still at higher risk for future detection of CIN 2-3 even if the
initial biopsy fails to detect it. It has also been shown that
immunohistochemical staining for p16INK4a can be reliably used as a surrogate
marker for infection with high risk human papillomavirus in cervical samples, and
that it can be used to enhance detection of CIN2-3 in cases where suspicion is
high. To evaluate the use of p16INK4a staining in cases of HSIL which were not
confirmed on initial biopsy, two pathologists rereviewed Pap and hematoxylin and
eosin preparations from all such cases seen within the preceding 3 years.
Immunohistochemical study for p16INK4a was performed and graded on representative
sections. The results were tabulated and analyzed. Of the identified 596 HSIL Pap
cases, 82% had HSIL on initial cervical specimens. Table 1 shows the 56 cases
included in the study with graded and stratified p16INK4a results. On review of
the p16INK4a slides, only 2 cases could be upgraded to HSIL/CIN2-3 from the
original diagnosis. p16INK4a 2-3+ was expressed more frequently in cases
initially interpreted on Pap as low-grade cervical lesion as compared with benign
(24 of 35 cases). In the younger than 24-yr-old group p16 2-3+ reactivity was
more frequent in benign and low-grade cervical lesion/CIN1 groups (benign: 3 of 5
cases, and CIN1: 6 of 8), and p16 negative reactivity was not seen. p16INK4a was
graded 0-1+ more frequently in specimens interpreted as benign in the older than
25 yr olds (10 of 16 cases). The study suggests some diagnostic benefit from the
use of p16INK4a immunohistochemical study on cervical specimens from women with a
HSIL Pap test without HSIL/CIN2-3 on original hematoxylin and eosin review.
PMID- 25844546
TI - Endocervical adenocarcinoma in situ presenting in fundal endometrial polyp: the
mother of all skip lesions.
AB - A 38-yr-old woman, with a previous history of low grade squamous intraepithelial
lesion in the cervix, presented with heavy menstrual bleeding. At hysteroscopy, a
fundal polyp was removed from the right cornu which displayed many glands lined
by atypical, mitotically active epithelium with features characteristic of
endocervical adenocarcinoma in situ (AIS) of intestinal subtype. Subsequent
cervical liquid-based cytology and colposcopically directed biopsies revealed no
causative lesion, but residual PreservCyt from the ThinPrep vial tested positive
for high risk HPV type other than HPV 16 and 18. Further biopsies from the
endocervical canal and base of the resected polyp showed intestinal type AIS,
while all those from the intervening anterior and posterior endometrial lining
exhibited normal endometrium only. Genomic DNA extracted from the endometrial
polyp and second set of endocervical biopsies tested positive for HPV 31, an
uncommon cause of endocervical glandular neoplasia. Endocervical AIS typically
arises in the transformation zone but may be found exclusively in the
endocervical canal and rarely as high as 30 mm from the ectocervix. Contiguous
spread into the lower uterine segment is known to occur, as are proximate so
called skip lesions. However, finding a 'skip' lesion 80 mm from the
transformation zone poses an interesting pathogenetic conundrum as well as a
therapeutic dilemma in a young patient desirous of retaining fertility. Issues
relating to pathogenesis include necessary metaplasia of the endometrial
glandular epithelium to 'susceptible' endocervical type epithelium within the
polyp or metastatic implantation of transformed endocervical glandular cells onto
the polyp. The current management plan involves regular hysteroscopic
surveillance of the uterine cavity.
PMID- 25844547
TI - Dyssynchronous secretory endometrial glands often show sporadically acquired
progesterone nonresponsiveness.
AB - Primary sporadic gene-inactivating events within the progesterone response
cascade might explain the presence of individual dyssynchronous (outlier) glands
commonly observed in a secretory background. We queried morphologically
dyssynchronous glands in mid-secretory endometrium with a series of markers
normally downregulated by progesterone. Seventy-nine mid-secretory endometrial
biopsies were stained with hematoxylin and eosin, MIB-1, PAX2, estrogen and
progesterone receptors, and PTEN. Aberrant staining of glands was independently
scored for each marker. Outlier glands overlapping between stains were
enumerated. A total of 63% of cases had hematoxylin and eosin stained outlier
glands (average 9), which often demonstrated failed progesterone-mediated
downregulation of PAX2 (43%), estrogen (40%), and/or progesterone receptors
(28%). Aberrations of progesterone response was seen in 70% to 85% of cases
overall, averaging 10 to 30 glands/affected case. The frequency and burden of
affected glands was similar to that seen for primary inactivating events of the
PAX2 and PTEN genes (35% and 41% of cases, respectively, averaging 32 and 38
glands per affected patient). Sporadic gene-inactivating events are common during
endometrial regeneration, and may cause morphologic changes unmasked by the
hormonal context. Some of these dyssynchronous "outlier" glands, whether evident
on hematoxylin and eosin stain or not, have an interrupted progesterone response.
PMID- 25844548
TI - Partial hydatidiform mole with extensive angiomatoid vessel configuration in a
first trimester miscarriage.
AB - We report a first trimester miscarriage (9 wk gestation) with a macroscopic grape
like aspect due to extensive angiomatoid changes with widened communicating thin
walled villous vessels. Fluorescence in situ hybridization analysis and
microsatellite analysis revealed a diandric triploidy of the trophoblastic
tissue, so this miscarriage is indeed a genetic partial hydatidiform mole. This
is remarkable since the typical morphologic hallmarks of partial hydatidiform
mole, especially enhanced trophoblastic proliferation and marked villous cistern
formation, were not prominent. The finding of extensive angiomatoid morphology is
to our knowledge an undescribed morphology of an early partial hydatidiform mole.
It serves as an example of the morphologic variability of this probably
underestimated condition that has a slightly elevated risk for the development of
gestational trophoblastic disease.
PMID- 25844549
TI - Simultaneous carcinomas of the breast and ovary: utility of Pax-8, WT-1, and
GATA3 for distinguishing independent primary tumors from metastases.
AB - Breast carcinomas rarely metastasize to the ovary and are even more rarely
present clinically as primary ovarian tumors. However, patients with breast
cancer not infrequently develop independent primary ovarian carcinomas. In these
cases, distinction between independent primaries and metastatic tumors is
crucial. Several comparative immunohistochemical studies have been reported, but
few included significant clinicopathologic data and none investigated cases of
ovarian and breast carcinomas from the same patients. In this study, we compared
18 cases of patients with bona fide independent breast and ovarian carcinomas (15
high-grade serous and 3 clear cell carcinomas), with 9 cases of patients with
known mammary carcinomas (7 lobular and 2 ductal carcinomas) metastatic to the
ovary. Immunohistochemical stains for Pax-8, WT-1, and GATA3 were carried out on
tissue microarrays (TMA). Most primary ovarian carcinomas were larger than the
metastatic tumors (P=0.001) and were diagnosed at an advanced stage. All primary
ovarian tumors showed marked nuclear pleomorphism, whereas only 2 metastatic
breast carcinomas had Grade 3 nuclei (P=0.000). The vast majority of ovarian
metastases (7/9) showed the typical pattern of lobular breast carcinoma. Pax-8
and WT-1 expression were found in 16 of 18 (88%) and 13 of 18 (72%) primary
ovarian carcinomas, respectively. In contrast, all primary ovarian carcinomas
were negative for GATA3. The 2 Pax-8-negative ovarian carcinomas were also
negative for WT-1. With the exception of 3 triple-negative carcinomas, all
primary breast carcinomas were positive for GATA3. All metastatic breast
carcinomas were positive for GATA3 and negative for Pax-8. WT-1 expression was
seen in only 1 of 9 metastatic breast carcinomas (11%). Patients with ovarian
metastases had worse prognosis than patients with independent breast and ovarian
carcinomas (P=0.000). Pax-8, WT-1, and GATA3 immunoreactions are useful in the
distinction between independent primaries and metastatic mammary carcinomas to
the ovary in the light of clinicopathologic findings.
PMID- 25844550
TI - Ovarian sex cord-stromal tumors in patients with probable or confirmed germline
DICER1 mutations.
AB - The DICER1 gene encodes an endoribonuclease involved in the production of mature
microRNAs which regulates gene expression through several mechanisms. Recent
studies have demonstrated somatic mutations in DICER1 in approximately 60% of
ovarian Sertoli-Leydig cell tumors. Furthermore, patients with germline mutations
in DICER1 are predisposed to developing a range of rare neoplasms including
ovarian sex cord-stromal tumors most of which have been classified as Sertoli
Leydig cell tumor. However, the histologic features of these tumors have not been
reported in detail. We describe the morphologic and immunophenotypic findings of
4 sex cord-stromal tumors arising in patients with proven or likely germline
DICER1 mutations including 3 individuals from 1 family. Three tumors showed
similar appearances characterized by marked architectural and cytologic
heterogeneity including sertoliform, juvenile granulosa cell tumor-like, and
unclassifiable elements. The remaining case mainly showed heterologous mucinous
epithelial and neuroendocrine differentiation with only a minor intermediate
grade Sertoli cell component. This tumor and one of the 3 former cases arose in
related patients with identical germline DICER1 mutations indicating that
additional factors influence tumor morphology. All tumors were positive for
steroidogenic factor-1 and FOXL2 on immunohistochemical analysis, whereas there
was more variable expression of inhibin, calretinin, CD56, CD99, and hormone
receptors. The present small series suggests that some ovarian Sertoli-Leydig
cell tumor associated with germline DICER1 mutations may show distinctive
histologic features in particular admixed Sertoli cell and juvenile granulosa
cell tumor-like features. Larger studies are required to establish whether
heterologous elements are also a more common feature of these tumors.
PMID- 25844551
TI - Article by Natalie Banet and Robert J. Kurman: Two types of ovarian cortical
inclusion cysts: proposed origin and possible role in ovarian serous
carcinogenesis; Int. J. Gynecol. Pathol. 2015;34:3-8.
PMID- 25844552
TI - Re: Article by Natalie Banet and Robert J. Kurman: Two types of ovarian cortical
inclusion cysts: proposed origin and possible role in ovarian serous
carcinogenesis; Int. J. Gynecol. Pathol. 2015;34:3-8.
PMID- 25844553
TI - History of gynecologic pathology XXVII: Dr Herbert Bradley Taylor.
PMID- 25844554
TI - Optimization of ultrasound-assisted extraction of pectinase enzyme from guava
(Psidium guajava) peel: Enzyme recovery, specific activity, temperature, and
storage stability.
AB - This study aimed to investigate the effects of the ultrasound-assisted extraction
conditions on the yield, specific activity, temperature, and storage stability of
the pectinase enzyme from guava peel. The ultrasound variables studied were
sonication time (10-30 min), ultrasound temperature (30-50 degrees C), pH (2.0
8.0), and solvent-to-sample ratio (2:1 mL/g to 6:1 mL/g). The main goal was to
optimize the ultrasound-assisted extraction conditions to maximize the recovery
of pectinase from guava peel with the most desirable enzyme-specific activity and
stability. Under the optimum conditions, a high yield (96.2%), good specific
activity (18.2 U/mg), temperature stability (88.3%), and storage stability
(90.3%) of the extracted enzyme were achieved. The optimal conditions were 20 min
sonication time, 40 degrees C temperature, at pH 5.0, using a 4:1 mL/g solvent
to-sample ratio. The study demonstrated that optimization of ultrasound-assisted
process conditions for the enzyme extraction could improve the enzymatic
characteristics and yield of the enzyme.
PMID- 25844555
TI - A classification of chronic pain for ICD-11.
PMID- 25844557
TI - Energetic-Energetic Cocrystals of Diacetone Diperoxide (DADP): Dramatic and
Divergent Sensitivity Modifications via Cocrystallization.
AB - Here we report a series of energetic-energetic cocrystals that incorporate the
primary explosive diacetone diperoxide (DADP) with a series of
trihalotrinitrobenzene explosives: 1:1 DADP/1,3,5-trichloro-2,4,6-trinitrobenzene
(TCTNB), 1:1 DADP/1,3,5-tribromo-2,4,6-trinitrobenzene (TBTNB), and 1:1
DADP/1,3,5-triiodo-2,4,6-trinitrobenzene (TITNB). Acetone peroxides are
attractive for their inexpensive and facile synthesis, but undesirable properties
such as poor stability, intractably high sensitivity and low density, an
indicator for low explosive power, have limited their application. Here through
cocrystallization the density, oxygen balance, and stability of DADP are
dramatically improved. Regarding sensitivity, in the case of the DADP/TCTNB
cocrystal, the high impact sensitivity of DADP is retained by the cocrystal,
making it a denser and less volatile form of DADP that remains viable as a
primary explosive. Conversely, the DADP/TITNB cocrystal features impact
sensitivity that is greatly reduced relative to both pure DADP and pure TITNB,
demonstrating for the first time an energetic cocrystal that is less sensitive to
impact than either of its pure components. This dramatic difference in cocrystal
sensitivities may stem from the significantly different halogen-peroxide
interactions seen in each cocrystal structure. These results highlight how
sensitivity is defined by complex relationships between inherent bond strengths
and solid-state properties, and cocrystal series such as that presented here
provide a powerful experimental platform to probe this relationship.
PMID- 25844556
TI - Impaired Muscle Mitochondrial Biogenesis and Myogenesis in Spinal Muscular
Atrophy.
AB - IMPORTANCE: The important depletion of mitochondrial DNA (mtDNA) and the general
depression of mitochondrial respiratory chain complex levels (including complex
II) have been confirmed, implying an increasing paucity of mitochondria in the
muscle from patients with types I, II, and III spinal muscular atrophy (SMA-I,
II, and -III, respectively). OBJECTIVE: To investigate mitochondrial dysfunction
in a large series of muscle biopsy samples from patients with SMA. DESIGN,
SETTING, AND PARTICIPANTS: We studied quadriceps muscle samples from 24 patients
with genetically documented SMA and paraspinal muscle samples from 3 patients
with SMA-II undergoing surgery for scoliosis correction. Postmortem muscle
samples were obtained from 1 additional patient. Age-matched controls consisted
of muscle biopsy specimens from healthy children aged 1 to 3 years who had
undergone analysis for suspected myopathy. Analyses were performed at the
Neuromuscular Unit, Istituto di Ricovero e Cura a Carattere Scientifico
Foundation Ca' Granda Ospedale Maggiore Policlinico-Milano, from April 2011
through January 2015. EXPOSURES: We used histochemical, biochemical, and
molecular techniques to examine the muscle samples. MAIN OUTCOMES AND MEASURES:
Respiratory chain activity and mitochondrial content. RESULTS: Results of
histochemical analysis revealed that cytochrome-c oxidase (COX) deficiency was
more evident in muscle samples from patients with SMA-I and SMA-II. Residual
activities for complexes I, II, and IV in muscles from patients with SMA-I were
41%, 27%, and 30%, respectively, compared with control samples (P < .005). Muscle
mtDNA content and cytrate synthase activity were also reduced in all 3 SMA types
(P < .05). We linked these alterations to downregulation of peroxisome
proliferator-activated receptor coactivator 1alpha, the transcriptional
activators nuclear respiratory factor 1 and nuclear respiratory factor 2,
mitochondrial transcription factor A, and their downstream targets, implying
depression of the entire mitochondrial biogenesis. Results of Western blot
analysis confirmed the reduced levels of the respiratory chain subunits that
included mitochondrially encoded COX1 (47.5%; P = .004), COX2 (32.4%; P < .001),
COX4 (26.6%; P < .001), and succinate dehydrogenase complex subunit A (65.8%; P =
.03) as well as the structural outer membrane mitochondrial porin (33.1%; P <
.001). Conversely, the levels of expression of 3 myogenic regulatory factors
muscle-specific myogenic factor 5, myoblast determination 1, and myogenin-were
higher in muscles from patients with SMA compared with muscles from age-matched
controls (P < .05). CONCLUSIONS AND RELEVANCE: Our results strongly support the
conclusion that an altered regulation of myogenesis and a downregulated
mitochondrial biogenesis contribute to pathologic change in the muscle of
patients with SMA. Therapeutic strategies should aim at counteracting these
changes.
PMID- 25844558
TI - A comparison of self-reported sexual risk behaviours between US civilian and
active duty military women.
AB - Women in the US military report a high prevalence of sexual risk behaviours, such
as binge drinking and new or multiple sexual partnerships. However, demographical
differences pose challenges to making comparisons with civilians. Two public-use
datasets were used to compare prevalence of sexual risk behaviours between
sexually active military and civilian women, after adjusting for demographic
factors. It was found that women in the military reported a higher prevalence of
binge drinking and new/multiple sexual partners as compared with civilians, which
suggests that military women are a high-risk group and the military environment
may at least partially facilitate these risk behaviours.
PMID- 25844559
TI - Malignant (Diffuse) Mesothelioma in Patients With Hematologic Malignancies: A
Clinicopathologic Study of 45 Cases.
AB - CONTEXT: Ionizing radiation has a role in the development of malignant
mesothelioma, in several epidemiologic studies, including patients with
hematologic malignancies. OBJECTIVE: To study the clinicopathologic
characteristics of patients with malignant mesothelioma and hematologic
malignancies with and without a history of radiotherapy. DESIGN: From a database
of approximately 3600 patients with malignant mesothelioma, we identified 45
patients (1%) who also had hematologic malignancies. We examined
clinicopathologic features and noted whether the patient had received
radiotherapy for malignancy, comparing those with and those without such
exposure. RESULTS: Among the 45 cases, 18 (40%) had Hodgkin lymphoma, 15 (33%)
had non-Hodgkin lymphoma, 10 (4%) had chronic lymphocytic leukemia, and 2 (22%)
had chronic myelogenous leukemia; 20 patients (44%) had a history of
radiotherapy, and 23 (51%) did not. Most patients with Hodgkin lymphoma (16 of
18; 90.0%) received radiation, whereas none of the patients with leukemia (0 of
12) and only 20% (3 of 15) of the patients with non-Hodgkin lymphoma did so.
Patients without radiation were older than patients who received radiotherapy
(median, 73 versus 54 years, respectively; P < .001), had a shorter interval from
diagnosis of hematologic malignancy to that of mesothelioma (median, 2 versus 24
years, respectively; P < .001), and had a shorter survival period (median, 6.0
versus 14.0 months, respectively; P = .02). Epithelial mesotheliomas were
proportionately more common in patients with a history of radiotherapy.
CONCLUSIONS: Patients with mesothelioma and hematologic malignancies with a
history of radiation tended to be younger, had a longer interval from diagnosis
of hematologic malignancy to that of mesothelioma, had a longer survival period,
and were more likely to have the epithelial variant compared with patients
without radiotherapy.
PMID- 25844560
TI - A Pilot Study on the Influence of Facial Expression on Measurements in Three
Dimensional Digital Surfaces of the Face in Infants With Cleft Lip and Palate.
AB - OBJECTIVE: Three-dimensional surface imaging is an increasingly popular modality
for face measurements in infants with cleft lip and palate. Infants are
noncompliant toward producing specific facial expressions, and selecting the
appropriate moment of acquisition is challenging. The objective was to estimate
amount and spatial distribution of deformation of the face due to facial
expression in infants with cleft lip and palate and provide recommendations for
an improved acquisition protocol, including a method of quality control in terms
of obtaining images with true neutral expression. MATERIAL AND METHODS: Three
dimensional surface images of ten 4-month-old infants with unrepaired cleft lip
and palate were obtained using a 3dMDface stereophotogrammetric system. For each
subject, five surface images judged as representing a neutral expression were
obtained during the same photo session. Mean and maximum deformations were
calculated. A formalized review was performed, allowing the image exhibiting the
"best" neutral expression to be selected, thus decreasing errors due to residual
facial expression. RESULTS: Deformation due to facial expression generally
increased from forehead to chin. The amount of deformation in three selected
regions were determined: nose (mean, 1 mm; maximum = 3 mm); cleft region (mean, 2
mm; maximum = 5 mm); chin region (mean, 5 mm; maximum = 12 mm). Analysis
indicated that introduction of a formalized review of images could reduce these
errors by a factor of 2. CONCLUSIONS: The continuous change of facial expression
in infants represents a substantial source of error; however, this may be reduced
by incorporating a formalized review into the acquisition protocol.
PMID- 25844561
TI - Primary Palatoplasty for Unilateral Cleft Lip and Palate Using Mucosal Grafts and
Flaps.
AB - The mucosal graft and flaps method (MG method) is a palatoplasty technique that
was developed for the purpose of improving maxillary growth in patients with
cleft palate. In the MG method, full-thickness buccal mucosa is grafted onto the
raw surface created by pushback palatoplasty. The method is unlikely to result in
severe scarring and has a favorable effect on maxillary growth. In addition, it
is unlikely to result in oronasal fistula and provides good speech results.
Overall, postive long-term treatment results have been obtained. Although the MG
method is technically difficult and requires a lengthy surgery, the technique is
considered to be effective for palate closure in terms of speech and maxillary
growth.
PMID- 25844562
TI - The Americleft Project: A Proposed Expanded Nasolabial Appearance Yardstick for 5
to 7-Year-Old Patients With Complete Unilateral Cleft Lip and Palate (CUCLP).
AB - OBJECTIVE: To develop a yardstick of reference photographs for nasolabial
appearance assessments of 5- to 7-year-old patients with complete unilateral
cleft lip and palate (CUCLP). DESIGN: Blind retrospective analysis of clinical
records and comparison to historical controls. PATIENTS: Subjects were two groups
of 6- to 12-year-olds (n = 124 and n = 135) and one group of 5- to 7-year-olds (n
= 149) with nonsyndromic CUCLP from three previous Americleft studies, including
cohorts from seven different cleft/craniofacial centers. INTERVENTIONS: All
patients received the infant management protocols of their respective centers.
Eleven trained and calibrated judges (five participated in all three studies) did
blind ratings of nasolabial appearance using the Asher-McDade method. MAIN
OUTCOME MEASURES: Patients receiving the most consistent ratings between judges,
selected first from the groups of 6- to 12-year-olds, were used to create a pilot
yardstick for eventual use in the third study of 5- to 7-year-olds. For each of
the Asher-McDade categories, 8 of the 5- to 7-year-old patients receiving the
most consistent scores between raters were ranked by 10 judges for a final
elimination to leave three per category. RESULTS: Using this method of successive
changes in rating methods, a new reference yardstick for nasolabial appearance
rating was established and linked to the original Asher-McDade method as well as
the single examples in a previously published yardstick for patients with CUCLP.
Pilot testing using the yardstick improved reliabilities. CONCLUSIONS: Use of an
expanded nasolabial yardstick of reference photographs representative of the
range of possibilities of each of the five Asher-McDade categories is now
available to see if reliability of these ratings can be improved.
PMID- 25844564
TI - Adolescent Turkish migrants' eating behavior in Germany: A comparison to
nonmigrants in the home and host countries based on the prototype-willingness
model.
AB - OBJECTIVES: The aim of the present research was to examine the regulation of
eating behavior among adolescents with a Turkish migration background living in
Germany in comparison with adolescent nonmigrants from the host (Germany) and
home country (Turkey). The prototype-willingness model (PWM) was chosen and
analyzed with respect to differences in mean levels and predictions of its social
cognitive factors. METHOD: Two studies were conducted. Study 1 was longitudinal
with 131 adolescent Turkish migrants and 303 Germans, whereas Study 2 was cross
sectional with 102 adolescent Turkish migrants and 270 Turks. Sociodemographic
information, PWM variables, and eating behavior were enquired via questionnaire.
Group differences in means and prediction patterns were analyzed using multiple
group structural equation modeling. Analyses were conducted separately
introducing PWM variables to eat either unhealthy (unhealthy model) or healthy
foods (healthy model). RESULTS: The studies show consistent differences in means
and predictions between Turkish migrants and Germans as well as Turks. The
regulation of Turkish migrants' eating behavior was found to be intentional,
whereas Germans and Turks showed both an impulsive and intentional regulation.
CONCLUSIONS: Effective interventions on healthy eating for Turkish migrants need
to be tailored according to their specific regulation of eating behavior.
PMID- 25844565
TI - Development and validation of the African American Women's Shifting Scale
(AAWSS).
AB - OBJECTIVE: The purpose of this research was to develop and validate an instrument
to measure shifting or self-altering strategies among African American women.
METHOD: A 13-item instrument was developed to measure aspects of shifting
phenomena based on the empirical literature, feedback from focus groups, and
cultural experts. The initial validation study, using principal axis analysis,
was conducted with a national sample of 318 African American women. A second
independent national sample of 190 African American women provided data for a
confirmatory factor analysis. RESULTS: Results indicated that the inventory was
composed of the following 3 factors: Strong Black Woman, Awareness of Shifting
Behavior, and Sensitivity to the Perceptions of Blacks. CONCLUSIONS: A structural
model was developed based on the Multicultural Assessment-Intervention Process
(MAIP) framework that allowed for the exploration of the shifting construct.
Implications for future research are discussed.
PMID- 25844567
TI - Competing mortality in cancer screening: a teachable moment.
PMID- 25844568
TI - Roster process review: a case study on the implications of preliminary findings.
AB - Rostering is an important process to enable efficient, effective and safe
delivery of health care, and one which receives little attention. The work
outlined in this case study demonstrates that the analysis of rostering processes
from a range of perspectives including the organisation, staff and the roster
manager can identify significant opportunities for improvement. Roster governance
is not universally applied, nor understood, which can result in dissonant
expectations between managers and staff and a lack of transparency in how and why
decisions about rostering are made. Redesigning roster processes can promote more
effective governance and improve organisational efficiency.
PMID- 25844566
TI - Impact of lifetime evaluated need on mental health service use among African
American emerging adults.
AB - OBJECTIVE: This study investigated the association between evaluated need and
mental health service use among African-American emerging adults, when
controlling for other predictor variables. METHOD: Secondary analysis of data
from the National Survey of American Life (2001-2003) was conducted. A nationally
representative sample of African-American emerging adults, ages 18 to 29 years (N
= 806), was assessed with the Composite International Diagnostic Interview. The
sample included females and males with a mean age of 23 years. Evaluated need was
determined by endorsement of mood, anxiety, substance use, or impulse control
diagnoses. Respondents who reported ever voluntarily using mental health or
general medical services to address these problems were considered to have used
services. RESULTS: Forty-seven percent of the sample demonstrated an evaluated
need for services, whereas a quarter of the sample used services in their
lifetime. Respondents who were females, had received religious/spiritual support,
and who had an evaluated need for services were significantly more likely to have
used services in their lifetime compared with males, those who had not received
religious/spiritual support, and those without a need for services. CONCLUSIONS:
Literature indicates that evaluated need is a strong predictor of mental health
service use, yet research examining its impact on service use among African
American emerging adults is limited. This study found that along with having an
evaluated need, this population was more likely to use services when supported by
a religious/spiritual leader. Mental health outreach and education that
incorporates the informal support systems identified by African American emerging
adults, particularly males, is needed.
PMID- 25844569
TI - Patient beliefs and behaviors about genomic risk for type 2 diabetes:
implications for prevention.
AB - Type 2 diabetes is a major health burden in the United States, and population
trends suggest this burden will increase. High interest in, and increased
availability of, testing for genetic risk of type 2 diabetes presents a new
opportunity for reducing type 2 diabetes risk for many patients; however, to
date, there is little evidence that genetic testing positively affects type 2
diabetes prevention. Genetic information may not fit patients' illness
representations, which may reduce the chances of risk-reducing behavior changes.
The present study aimed to examine illness representations in a clinical sample
who are at risk for type 2 diabetes and interested in genetic testing. The
authors used the Common Sense Model to analyze survey responses of 409 patients
with type 2 diabetes risk factors. Patients were interested in genetic testing
for type 2 diabetes risk and believed in its importance. Most patients believed
that genetic factors are important to developing type 2 diabetes (67%), that diet
and exercise are effective in preventing type 2 diabetes (95%), and that
lifestyle changes are more effective than drugs (86%). Belief in genetic
causality was not related to poorer self-reported health behaviors. These results
suggest that patients' interest in genetic testing for type 2 diabetes might
produce a teachable moment that clinicians can use to counsel behavior change.
PMID- 25844570
TI - Catch-up growth in low-birthweight infants: friend or foe?
PMID- 25844571
TI - Phytomedicines (medicines derived from plants) for sickle cell disease.
AB - BACKGROUND: Sickle cell disease, a common recessively inherited haemoglobin
disorder, affects people from sub-Saharan Africa, the Middle East, Mediterranean
basin, Indian subcontinent, Caribbean and South America. It is associated with
complications and a reduced life expectancy. Phytomedicines (medicine derived
from plants in their original state) encompass many of the plant remedies from
traditional healers which the populations most affected would encounter. There
has been little systematic appraisal of their benefits. This is an update of a
Cochrane Review first published in 2010 and updated in 2013. OBJECTIVES: To
assess the benefits and risks of phytomedicines in people with sickle cell
disease of all types, of any age, in any setting. SEARCH METHODS: We searched the
Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials
Register, the International Standard Randomised Controlled Trial Number Register
(ISRCTN) and the Allied and Complimentary Medicine Database (AMED).Dates of most
recent searches: Haemoglobinopathies Trials Register: 13 October 2014; ISRCTN: 17
January 2015; AMED: 20 January 2015. SELECTION CRITERIA: Randomised or quasi
randomised trials with participants of all ages with sickle cell disease, in all
settings, comparing the administration of phytomedicines, by any mode to placebo
or conventional treatment, including blood transfusion and hydroxyurea. DATA
COLLECTION AND ANALYSIS: Both authors independently assessed trial quality and
extracted data. MAIN RESULTS: Two trials (182 participants) and two
phytomedicines Niprisan((r)) (also known as Nicosan((r))) and Ciklavit((r)) were
included. The Phase IIB (pivotal) trial suggests that Niprisan((r)) was effective
in reducing episodes of severe painful sickle cell disease crisis over a six
month period. It did not affect the risk of severe complications or the level of
anaemia. No serious adverse effects were reported. The single trial of Cajanus
cajan (Ciklavit((r))) reported a possible benefit to individuals with painful
crises, and a possible adverse effect (non-significant) on the level of anaemia.
AUTHORS' CONCLUSIONS: While Niprisan((r)) appeared to be safe and effective in
reducing severe painful crises over a six-month follow-up period, further trials
are required to assess its role in the management of people with sickle cell
disease and the results of its multicentre trials are awaited. Currently no
conclusions can be made regarding the efficacy of Ciklavit((r)). Based on the
published results for Niprisan((r)) and in view of the limitations in data
collection and analysis of both trials, phytomedicines may have a potential
beneficial effect in reducing painful crises in sickle cell disease. This needs
to be further validated in future trials. More trials are required on the safety
and efficacy of phytomedicines used in managing sickle cell disease.
PMID- 25844572
TI - Is dissonance reduction a special case of fluid compensation? Evidence that
dissonant cognitions cause compensatory affirmation and abstraction.
AB - Cognitive dissonance theory shares much in common with other perspectives that
address anomalies, uncertainty, and general expectancy violations. This has led
some theorists to argue that these theories represent overlapping psychological
processes. If responding to dissonance and uncertainty occurs through a common
psychological process, one should expect that the behavioral outcomes of feeling
uncertain would also apply to feelings of dissonance, and vice versa. One
specific prediction from the meaning maintenance model would be that cognitive
dissonance, like other expectancy violations, should lead to the affirmation of
unrelated beliefs, or the abstraction of unrelated schemas when the dissonant
event cannot be easily accommodated. This article presents 4 studies (N = 1124)
demonstrating that the classic induced-compliance dissonance paradigm can lead
not only to a change of attitudes (dissonance reduction), but also to (a) an
increased reported belief in God (Study 2), (b) a desire to punish norm-violators
(Study 1 and 3), (c) a motivation to detect patterns amid noise (Study 3), and
(d) polarizing support of public policies among those already biased toward a
particular side (Study 4). These results are congruent with theories that propose
content-general fluid compensation following the experience of anomaly, a finding
not predicted by dissonance theory. The results suggest that dissonance reduction
behaviors may share psychological processes described by other theories
addressing violations of expectations.
PMID- 25844573
TI - Stereotype validation: the effects of activating negative stereotypes after
intellectual performance.
AB - With regard to intellectual performance, a large body of research has shown that
stigmatized group members may perform more poorly when negative, self-relevant
stereotypes become activated prior to a task. However, no research to date has
identified the potential ramifications of stereotype activation that happens
after-rather than before-a person has finished performing. Six studies examined
how postperformance stereotype salience may increase the certainty individuals
have in evaluations of their own performance. In the current research, the
accessibility of gender or racial stereotypes was manipulated after participants
completed either a difficult math test (Studies 1-5) or a test of child-care
knowledge (Study 6). Consistent with predictions, stereotype activation was found
to increase the certainty that women (Studies 1, 2, 4, and 5), African Americans
(Study 3), and men (Study 6) had toward negative evaluations of their own test
performance. These effects emerged when performance-related perceptions were
stereotype consistent rather than inconsistent (Studies 1-6) and were found to be
most pronounced among those who were highly identified with the stereotyped group
(Study 5). Furthermore, greater certainty-triggered by negative stereotypes
predicted lowered domain-relevant beliefs (Studies 1, 2, 3, and 6) and
differential exposure to domain-relevant stimuli (Studies 4 and 5).
PMID- 25844574
TI - Using the IAT to predict ethnic and racial discrimination: small effect sizes of
unknown societal significance.
AB - Greenwald, Banaji, and Nosek (2015) present a reanalysis of the meta-analysis by
Oswald, Mitchell, Blanton, Jaccard, and Tetlock (2013) that examined the effect
sizes of Implicit Association Tests (IATs) designed to predict racial and ethnic
discrimination. We discuss points of agreement and disagreement with respect to
methods used to synthesize the IAT studies, and we correct an error by Greenwald
et al. that obscures a key contribution of our meta-analysis. In the end, all of
the meta-analyses converge on the conclusion that, across diverse methods of
coding and analyzing the data, IAT scores are not good predictors of ethnic or
racial discrimination, and explain, at most, small fractions of the variance in
discriminatory behavior in controlled laboratory settings. The thought
experiments presented by Greenwald et al. go well beyond the lab to claim
systematic IAT effects in noisy real-world settings, but these hypothetical
exercises depend crucially on untested and, arguably, untenable assumptions.
PMID- 25844575
TI - "Two souls, two thoughts," two self-schemas: double consciousness can have
positive academic consequences for African Americans.
AB - African Americans can experience a double consciousness-the two-ness of being an
American and an African American. The present research hypothesized that: (a)
double consciousness can function as 2 self-schemas-an independent self-schema
tied to mainstream American culture and an interdependent self-schema tied to
African American culture, and (b) U.S. educational settings can leverage an
interdependent self-schema associated with African American culture through
inclusive multicultural practices to facilitate positive academic consequences.
First, a pilot experiment and Studies 1 and 2 provided evidence that double
consciousness can be conceptualized as 2 self-schemas. That is, African Americans
shifted their behavior (e.g., cooperation) in schema-relevant ways from more
independent when primed with mainstream American culture to more interdependent
when primed with African American culture. Then, Studies 3 and 4 demonstrated
that incorporating African American culture within a university setting enhanced
African Americans' persistence and performance on academic-relevant tasks.
Finally, using the Gates Millennium Scholars dataset (Cohort 1), Study 5
conceptually replicated Studies 3 and 4 and provided support for one process that
underlies the observed positive academic consequences. Specifically, Study 5
provided evidence that engagement with African American culture (e.g.,
involvement with cultural events/groups) on college campuses makes an
interdependent self-schema more salient that increases African American students'
sense of academic fit and identification, and, in turn, enhances academic
performance (self-reported grades) and persistence (advanced degree enrollment in
a long-term follow-up). The discussion examines double consciousness as a basic
psychological phenomenon and suggests the intra- and intergroup benefits of
inclusive multicultural settings.
PMID- 25844576
TI - Having "been there" doesn't mean I care: when prior experience reduces compassion
for emotional distress.
AB - The current research found that participants who had previously endured an
emotionally distressing event (e.g., bullying) more harshly evaluated another
person's failure to endure a similar distressing event compared with participants
with no experience enduring the event or those currently enduring the event.
These effects emerged for naturally occurring (Studies 1, 3, and 4) and
experimentally induced (Study 2) distressing events. This effect was driven by
the tendency for those who previously endured the distressing event to view the
event as less difficult to overcome (Study 3). Moreover, we demonstrate that the
effect is specific to evaluations of perceived failure: Compared with those with
no experience, people who previously endured a distressing event made less
favorable evaluations of an individual failing to endure the event, but made more
favorable evaluations of an individual managing to endure the event (Study 4).
Finally, we found that people failed to anticipate this effect of enduring
distress, instead believing that individuals who have previously endured
emotionally distressing events would most favorably evaluate others' failures to
endure (Study 5). Taken together, these findings present a paradox such that, in
the face of struggle or defeat, the people we seek for advice or comfort may be
the least likely to provide it.
PMID- 25844577
TI - Implicit theories about willpower predict self-regulation and grades in everyday
life.
AB - Laboratory research shows that when people believe that willpower is an abundant
(rather than highly limited) resource they exhibit better self-control after
demanding tasks. However, some have questioned whether this "nonlimited" theory
leads to squandering of resources and worse outcomes in everyday life when
demands on self-regulation are high. To examine this, we conducted a longitudinal
study, assessing students' theories about willpower and tracking their self
regulation and academic performance. As hypothesized, a nonlimited theory
predicted better self-regulation (better time management and less
procrastination, unhealthy eating, and impulsive spending) for students who faced
high self-regulatory demands. Moreover, among students taking a heavy course
load, those with a nonlimited theory earned higher grades, which was mediated by
less procrastination. These findings contradict the idea that a limited theory
helps people allocate their resources more effectively; instead, it is people
with the nonlimited theory who self-regulate well in the face of high demands.
PMID- 25844578
TI - Dual passivation of intrinsic defects at the compound semiconductor/oxide
interface using an oxidant and a reductant.
AB - Studies have shown that metal oxide semiconductor field-effect transistors
fabricated utilizing compound semiconductors as the channel are limited in their
electrical performance. This is attributed to imperfections at the
semiconductor/oxide interface which cause electronic trap states, resulting in
inefficient modulation of the Fermi level. The physical origin of these states is
still debated mainly because of the difficulty in assigning a particular
electronic state to a specific physical defect. To gain insight into the exact
source of the electronic trap states, density functional theory was employed to
model the intrinsic physical defects on the InGaAs (2 * 4) surface and to model
the effective passivation of these defects by utilizing both an oxidant and a
reductant to eliminate metallic bonds and dangling-bond-induced strain at the
interface. Scanning tunneling microscopy and spectroscopy were employed to
experimentally determine the physical and electronic defects and to verify the
effectiveness of dual passivation with an oxidant and a reductant. While
subsurface chemisorption of oxidants on compound semiconductor substrates can be
detrimental, it has been shown theoretically and experimentally that oxidants are
critical to removing metallic defects at oxide/compound semiconductor interfaces
present in nanoscale channels, oxides, and other nanostructures.
PMID- 25844579
TI - Polyisobutylene-Based pH-Responsive Self-Healing Polymeric Gels.
AB - This work demonstrates the successful application of dynamic covalent chemistry
for the construction of self-healing gels from side-chain primary amine leucine
pendant diblock copolymers of polyisobutylene (PIB) ((P(H2N-Leu-HEMA)-b-PIB)) in
the presence of PIB based dialdehyde functionalized cross-linker (HOC-PIB-CHO)
through imine (-HC?N-) bond formation without aiding any external stimuli. Gels
were synthesized in 1,4-dioxane at room temperature at varied wt % of gelator
concentration, [H2N]/[CHO] ratios and molecular weight of the block segments. The
mechanical property of gels was examined by rheological measurements. We observed
higher value of storage modulus (G') than the loss modulus (G") within the
linearity limits of deformation, indicating the rheological behavior in the gel
is dominated by an elastic property rather than a viscous property. The G' values
significantly depend upon the extent of cross-linking in the gel network. To
establish self-healing property of the gels, rheology analysis through step
strain measurements (strain = 0.1 to 200%) at 25 degrees C was performed. The
polymeric gel network shows reversible sol-gel transition for several cycles by
adjusting the pH of the medium with the help of hydrochloric acid (HCl) and
triethylamine (Et3N) triggers. FT-IR spectroscopy established formation of imine
bonds in the gel network and these gels showed poor swelling behavior in various
organic solvents because of the small interstitial porosity, confirmed by field
emission-scanning electron microscopy (FE-SEM).
PMID- 25844580
TI - Impact of prenatal exposure to psychotropic drugs on neonatal outcome in infants
of mothers with serious psychiatric illnesses.
AB - OBJECTIVE: To assess whether prenatal exposure to 4 major classes of psychotropic
drugs compared with no exposure differed with respect to neonatal outcome.
METHOD: We used the database collected from 13 mother-baby units (MBUs) by the
French Network of MBUs. The Marce Clinical Checklist was used to collect data
from maternal interview and clinical record with respect to maternal demographic
and clinical characteristics, prenatal exposure to psychotropic drugs, and
neonatal outcome (birth weight, preterm birth, neonatal hospitalization).
Multivariate logistic regression was used to explore the independent impact of
each therapeutic class of psychotropic drug (antipsychotics, antidepressants,
mood stabilizers, and anxiolytics/hypnotics) on infant outcomes. All the models
were adjusted for maternal confounding factors. RESULTS: The sample included
1,071 women and their infants. Nearly half (40.2%) used at least 1 psychotropic
drug during pregnancy. The risk of low birth weight was increased by antenatal
exposure to mood stabilizers (adjusted odds ratio [aOR] = 2.04, 95% confidence
interval [CI] = 1.03-4.04, P = .04). The risk of neonatal hospitalization was
increased by prenatal exposure to antipsychotics (aOR = 1.74, 95% CI = 1.19-2.54,
P = .004), antidepressants (aOR = 1.59, 95% CI = 1.05-2.41, P = .03) or
anxiolytics/hypnotics (aOR = 1.89, 95% CI = 1.30-2.75, P = .001), independent of
birth weight and term delivery status. CONCLUSIONS: Infants exposed to
psychotropic drugs during pregnancy have less optimal neonatal outcome than
unexposed infants and should be considered as a high-risk population.
PMID- 25844581
TI - N-heterocyclic carbene nitric oxide radicals.
AB - N-Heterocyclic carbene-stabilized nitric oxide radicals were prepared by direct
addition of nitric oxide to two N-heterocyclic carbenes in solution phase. The
compounds were fully characterized by X-ray crystallography and EPR. The nitric
oxide moiety in the solid compounds obtained can be thermally transferred to
another N-heterocyclic carbene, suggesting potential applications to NO delivery.
PMID- 25844582
TI - We can do better for our veterans' health care.
PMID- 25844583
TI - Orthopedic registries: second thoughts.
PMID- 25844584
TI - The value of national and hospital registries.
PMID- 25844585
TI - Using wearable technology to record surgical videos.
PMID- 25844586
TI - Arthroscopic anterior cruciate ligament reconstruction using a flexible guide pin
with a rigid reamer.
AB - Successful anterior cruciate ligament reconstruction depends heavily on accurate
placement of the graft within the anatomical insertion of the native anterior
cruciate ligament. Inaccurate placement can lead to graft failure and recurrent
instability. Flexible guide pins and reamers have been developed to overcome some
of the limitations of using transtibial and anteromedial portals to drill femoral
tunnels. Early in our experience with flexible instruments, reamer breakage
caused complications. We therefore developed a technique that uses a flexible
guide pin with a rigid reamer to place the femoral tunnel in an anatomical
position. This technique allows placement of longer anatomical tunnels through an
anteromedial portal, reduces time spent with the knee in hyperflexion, provides
better viewing, poses less risk of damage to the articular cartilage and
neurovascular structures, and at a lower cost with less risk of reamer breakage.
PMID- 25844587
TI - The importance of sex of patient in the management of femoroacetabular
impingement.
AB - Femoroacetabular impingement (FAI), a recently described hip condition in
adolescents and young adults, typically manifests as activity-related hip pain.
Characteristic physical findings include limited passive internal rotation of the
affected hip and a positive impingement sign. Diagnostic imaging may reveal cam
and/or pincer lesions, and associated intra-articular pathology (eg, labral tear,
chondral damage) is common. When nonoperative treatment fails to adequately
alleviate symptoms, surgery may be warranted. Both open and arthroscopic
techniques have been effective. As our understanding of FAI continues to evolve,
sex-based differences in incidence, presentation, and outcomes for patients with
FAI have become apparent. Understanding the different ways in which males and
females may present with FAI and then changing clinical practice patterns to
accommodate these sexual dimorphisms will likely result in improved outcomes for
each patient with symptomatic FAI.
PMID- 25844588
TI - In vitro and in situ characterization of arthroscopic loop security and knot
security of braided polyblend sutures: a biomechanical study.
AB - We conducted a study to evaluate biomechanical performance during destructive
testing of several different suture materials in various arthroscopic knot
configurations under both in vitro and in situ conditions. Surgeons of different
levels of experience tied the knots. Three different arthroscopic knots (static
surgeon's, Weston, Tennessee slider) with 3 reverse half-hitches on alternating
posts were tested using Fiberwire, ForceFiber, Orthocord, and Ultrabraid suture
materials under both in vitro and in situ (blood plasma at 37 degrees C)
conditions. Three surgeons of different experience levels tied the knots on a
post 30 mm in circumference. A single load-to-failure test was performed. There
were no significant in vitro-in situ differences for Ultrabraid in the different
knot configurations or with the different experience levels. Surgeon B
(intermediate experience) showed no significant differences between test
conditions for any knot configuration or suture material. With Tennessee slider
knots, surgeon C (least experience) showed significantly lower clinical failure
load under both test conditions and had a higher percentage of complete knot
slippage. Surgeon B had no knot slippage with use of Fiberwire. Both the aqueous
environment and the surgeon's familiarity with certain knots have an effect on
knot security.
PMID- 25844589
TI - Extensor pollicis longus ruptures in distal radius fractures: clinical and
cadaveric studies with a new therapeutic intervention.
AB - We conducted a study to evaluate aspiration of the third dorsal compartment as a
therapeutic option for preventing extensor pollicis longus ruptures in
association with distal radius fractures. A cadaveric model with a nondisplaced
distal radius fracture was created, and radiopaque (Hypaque) dye was injected
into the fracture site. Pressure readings were taken from the third dorsal
compartment before and after dye injection. The compartment was aspirated with an
18-gauge needle, and compartment pressures were measured again. There was a
significant decrease in pressures after aspiration. Results in our cadaveric
model were consistent with those in in vitro decompression of the third dorsal
compartment. Clinical studies may determine that in-office needle aspiration is
beneficial in preventing extensor pollicis longus rupture in nondisplaced distal
radius fractures.
PMID- 25844590
TI - Greater auricular nerve palsy after arthroscopic anterior-inferior and posterior
inferior labral tear repair using beach-chair positioning and a standard
universal headrest.
AB - Shoulder arthroscopy is a common treatment for numerous different pathologies. An
iatrogenic nerve injury that occurs during shoulder arthroscopy is more common
than previously recognized. However, though many nerve pathologies are
increasingly being recognized, reported cases of greater auricular nerve injury
are limited. For instance, a case of greater auricular nerve palsy was reported
in only 2 series that used a horseshoe headrest. One set of authors discontinued
and recommended against use of this headrest, and the other recommended a
headrest redesign. Here we report on a case of greater auricular nerve palsy that
occurred after the patient's anterior-inferior and posterior-inferior labral tear
was arthroscopically repaired using beach-chair positioning and a standard
universal headrest. The palsy resulted in numbness and dysesthesia, which
lessened gradually over 3 months after surgery and was completely resolved by 6
months.
PMID- 25844591
TI - Lumbar degenerative disc disease and tibiotalar joint arthritis: a 710-specimen
postmortem study.
AB - Research has associated lumbar spinal disease with lower extremity arthrosis.
These studies focused solely on the lumbar spine's connection with hip or knee
pathology, failing to investigate potential ankle relationships. We specifically
explored the interplay between lumbar disc degeneration and tibiotalar joint
arthritis. Lumbar disc degeneration and tibiotalar joint arthritis was graded 0
to 4, according to osteophytosis of the vertebral rim and talar surface in 710
randomly selected cadaveric specimens. We corrected for confounding factors of
age, sex, race, and height. A significant association was found between lumbar
disc degeneration and tibiotalar joint arthritis (P < .01). Lumbar disc
degeneration encompassing 3 intervetebral discs demonstrated the highest odds for
development of severe tibiotalar joint arthritis. Severe lumbar degenerative disc
disease was more prevalent than severe tibiotalar joint arthritis in individuals
age 20 years and older. Furthermore, the presence of severe lumbar degeneration
significantly predisposes individuals to the development of severe ankle
arthritis (P < .05). Gait changes resulting from disc degeneration or neural
compression in the lumbar spine may play a role in ankle osteoarthritis
development. This association must be considered when treating patients with
lumbar disc degeneration and leg pain.
PMID- 25844592
TI - Comparison of locked plate fixation and nonoperative management for displaced
proximal humerus fractures in elderly patients.
AB - Use of locked plate fixation for proximal humerus fractures in elderly patients
has increased markedly in recent years. We conducted a study to compare outcomes
of operative (locked plate fixation) and nonoperative management of these
fractures. From our database, we identified 207 displaced proximal humerus
fractures that met all inclusion and exclusion criteria. For patients who
accepted our invitation to return for evaluation, clinical outcome was assessed
using several questionnaires: Constant; DASH (Disabilities of the Arm, Shoulder,
and Hand); SMFA (Short Musculoskeletal Functional Assessment); and Patient
Reported Outcomes Measurement Information System (PROMIS) Physical Function
Computer Adaptive Test. Of the 207 patients, 61 were managed operatively and 146
nonoperatively. Operative patients had lower rates of malunion but higher rates
of complications, which included screw perforation, loss of fixation, infection,
and secondary surgical procedures. Forty-seven patients (a mix of operative and
nonoperative) accepted our invitation to return for clinical evaluation at a mean
follow-up of 3.3 years. The 2 groups' clinical outcomes were similar.
PMID- 25844593
TI - Massive baker cyst resulting in tibial nerve compression neuropathy secondary to
polyethylene wear disease.
AB - Symptomatic synovial cyst formation is an infrequent, late complication after
total knee arthroplasty. Most often, these cysts are found incidentally. However,
rarely they may become larger leading to significant pain and disability. The
formation of gigantic cysts necessitating revision knee surgery has been detailed
in a few case reports. To the author's knowledge, this is the first report in the
medical literature that describes peripheral neuropathy of the tibial nerve
secondary to a massive Baker cyst after total knee replacement.
PMID- 25844594
TI - Failure of artelon interposition arthroplasty after partial trapeziectomy: a case
report with histologic and immunohistochemical analysis.
AB - Artelon is a degradable biomaterial used for the treatment of osteoarthritis in
the carpometacarpal joint of the thumb. The device reportedly works through 2
modes of action-stabilization of the carpometacarpal joint by augmentation of the
joint capsule and by formation of a new articular surface at the
trapeziometacarpal interface. We present a patient with late failure of
arthroscopic hemitrapeziectomy and Artelon interposition that required surgical
excision of the Artelon implant and trapeziectomy 4 years postoperatively. Gross
and histologic evaluation of the explanted Artelon implant and remaining
trapezium revealed lack of articular resurfacing by hyaline ingrowth.
PMID- 25844595
TI - Successful surgical treatment of an intraneural ganglion of the common peroneal
nerve.
AB - Intraneural ganglion cysts of peripheral nerves occurring within the epineural
sheath are rare, and their mechanism of formation and treatment options are
debated. We present a case of a 41-year-old man who presented with a complaint of
lateral-sided left knee pain with numbness on the lateral side of the foot who
was diagnosed with an intraneural ganglion of the common peroneal nerve (CPN). He
was treated initially with common peroneal epineural decompression only to have
symptoms recur 6 weeks postoperatively. The patient was subsequently treated
utilizing the suggestions of the "unified articular theory," which proposes a
small recurrent articular branch of the CPN as the source of cyst fluid. This
branch was surgically detached, leading to complete alleviation of his symptoms.
When the patient was reevaluated 2 years postoperatively, his preoperative
symptoms had resolved, and a follow-up magnetic resonance image showed resolution
of the enlargement of the CPN.
PMID- 25844596
TI - Revision anterior cruciate ligament reconstruction with bone-patellar tendon-bone
allograft and extra-articular iliotibial band tenodesis.
AB - Revision anterior cruciate ligament (ACL) reconstruction is a technically
demanding procedure with outcomes that generally fail to reach those seen with
primary ACL reconstruction. With most index procedures using autograft tissue, it
is not uncommon for allograft tissue to be required for revision ACL
reconstruction. Compared with autografts, allografts take longer to incorporate
and lead to more episodes of instability. In this article, we describe
ipsilateral iliotibial band tenodesis performed to augment use of bone-patellar
tendon-bone allograft in revision ACL reconstruction. This technique adds
rotational stability to protect the allograft tissue while it incorporates.
PMID- 25844597
TI - A systematic review of tibialis anterior tendon rupture treatments and outcomes.
AB - Tibialis anterior (TA) tendon rupture is a relatively rare injury that has been
documented primarily in case reports. This article is the first large systematic
review of the literature on treatment techniques for subcutaneous rupture of TA
tendons. Studies for review were identified through a PubMed search. Eligible
studies involved cases of closed tendon rupture. Of the 87 cases in the study, 72
were treated with surgery, 15 with conservative measures. Mean age was 63.9 years
(surgery group) and 72.4 years (conservative treatment group). Primary repair was
used most often for newer injuries, autograft most often for older injuries.
Operative repair of subcutaneous TA tendon rupture leads to successful outcomes
in many patients. A surgeon who is deciding which operative technique to use for
a patient should consider the age of the injury and the findings of
intraoperative assessment for tendon necrosis.
PMID- 25844598
TI - Superior Conductive Solid-like Electrolytes: Nanoconfining Liquids within the
Hollow Structures.
AB - The growth and proliferation of lithium (Li) dendrites during cell recharge are
currently unavoidable, which seriously hinders the development and application of
rechargeable Li metal batteries. Solid electrolytes with robust mechanical
modulus are regarded as a promising approach to overcome the dendrite problems.
However, their room-temperature ionic conductivities are usually too low to reach
the level required for normal battery operation. Here, a class of novel solid
electrolytes with liquid-like room-temperature ionic conductivities (>1 mS cm(
1)) has been successfully synthesized by taking advantage of the unique
nanoarchitectures of hollow silica (HS) spheres to confine liquid electrolytes in
hollow space to afford high conductivities (2.5 mS cm(-1)). In a symmetric
lithium/lithium cell, the solid-like electrolytes demonstrate a robust
performance against the Li dendrite problem, preventing the cell from short
circuiting at current densities ranging from 0.16 to 0.32 mA cm(-2) over an
extended period of time. Moreover, the high flexibility and compatibility of HS
nanoarchitectures, in principle, enables broad tunability to choose desired
liquids for the fabrication of other kinds of solid-like electrolytes, such as
those containing Na(+), Mg(2+), or Al(3+) as conductive media, providing a useful
alternative strategy for the development of next generation rechargeable
batteries.
PMID- 25844600
TI - Pre-clinical evaluation of the MDM2-p53 antagonist RG7388 alone and in
combination with chemotherapy in neuroblastoma.
AB - Neuroblastoma is a predominantly p53 wild-type (wt) tumour and MDM2-p53
antagonists offer a novel therapeutic strategy for neuroblastoma patients. RG7388
(Roche) is currently undergoing early phase clinical evaluation in adults. This
study assessed the efficacy of RG7388 as a single-agent and in combination with
chemotherapies currently used to treat neuroblastoma in a panel of neuroblastoma
cell lines. RG7388 GI50 concentrations were determined in 21 p53-wt and mutant
neuroblastoma cell lines of varying MYCN, MDM2 and p14(ARF) status, together with
MYCN-regulatable Tet21N cells. The primary determinant of response was the
presence of wt p53, and overall there was a >200-fold difference in RG7388 GI50
concentrations for p53-wt versus mutant cell lines. Tet21N MYCN+ cells were
significantly more sensitive to RG7388 compared with MYCN- cells. Using median
effect analysis in 5 p53-wt neuroblastoma cell lines, selected combinations of
RG7388 with cisplatin, doxorubicin, topotecan, temozolomide and busulfan were
synergistic. Furthermore, combination treatments led to increased apoptosis, as
evident by higher caspase-3/7 activity compared to either agent alone. These data
show that RG7388 is highly potent against p53-wt neuroblastoma cells, and
strongly supports its further evaluation as a novel therapy for patients with
high-risk neuroblastoma and wt p53 to potentially improve survival and/or reduce
toxicity.
PMID- 25844599
TI - Molecular profiling of prostate cancer derived exosomes may reveal a predictive
signature for response to docetaxel.
AB - Docetaxel is a cornerstone treatment for metastatic, castration resistant
prostate cancer (CRPC) which remains a leading cause of cancer-related deaths,
worldwide. The clinical usage of docetaxel has resulted in modest gains in
survival, primarily due to the development of resistance. There are currently no
clinical biomarkers available that predict whether a CRPC patient will respond or
acquire resistance to this therapy. Comparative proteomics analysis of exosomes
secreted from DU145 prostate cancer cells that are sensitive (DU145 Tax-Sen) or
have acquired resistance (DU145 Tax-Res) to docetaxel, demonstrated significant
differences in the amount of exosomes secreted and in their molecular
composition. A panel of proteins was identified by proteomics to be
differentially enriched in DU145 Tax-Res compared to DU145 Tax-Sen exosomes and
was validated by western blotting. Importantly, we identified MDR-1, MDR-3,
Endophilin-A2 and PABP4 that were enriched only in DU145 Tax-Res exosomes. We
validated the presence of these proteins in the serum of a small cohort of
patients. DU145 cells that have uptaken DU145 Tax-Res exosomes show properties of
increased matrix degradation. In summary, exosomes derived from DU145 Tax-Res
cells may be a valuable source of biomarkers for response to therapy.
PMID- 25844601
TI - Aquaporin 1 and 5 expression decreases during human intervertebral disc
degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells.
AB - Objectives of this study were to investigate whether AQP1 and AQP5 expression is
altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate
their expression in NP cells. AQP expression was measured in human tissues from
different degenerative grades; regulation by hypoxia and HIF-1 was studied using
promoter analysis and gain- and loss-of-function experiments. We show that both
AQPs are expressed in the disc and that mRNA and protein levels decline with
human disease severity. Bioinformatic analyses of AQP promoters showed multiple
evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter
activity or expression of either AQP. While genomic chromatin immunoprecipitation
showed limited binding of HIF-1alpha to conserved HREs, their mutation did not
suppress promoter activities. Stable HIF-1alpha suppression significantly
decreased mRNA and protein levels of both AQPs, but HIF-1alpha failed to induce
AQP levels following accumulation. Together, our results demonstrate that AQP1
and AQP5 expression is sensitive to human disc degeneration and that HIF-1alpha
uniquely maintains basal expression of both AQPs in NP cells, independent of
oxemic tension and HIF-1 binding to promoter HREs. Diminished HIF-1 activity
during degeneration may suppress AQP levels in NP cells, compromising their
ability to respond to extracellular osmolarity changes.
PMID- 25844602
TI - miR-942 promotes cancer stem cell-like traits in esophageal squamous cell
carcinoma through activation of Wnt/beta-catenin signalling pathway.
AB - The Wnt/beta-catenin signalling pathway is known to play a vital role in the
maintenance of cancer stem cells (CSCs), which are reported to be the origin of
malignant cancers, and result in poor prognosis of multiple kinds of cancer.
Therefore, it is of great importance to illuminate the mechanism by which the
Wnt/beta-catenin pathway regulates the cancer stem cell-like traits in cancers.
Here, we report that miR-942 is significantly upregulated in esophageal squamous
cell carcinoma (ESCC), and miR-942 levels are associated with poor prognosis in
ESCC patients. Overexpression of miR-942 promotes, whereas inhibition of miR-942
decreases, the tumor sphere formation, the CD90+ subpopulation cells and the
expression of pluripotency associated markers. Moreover, in vivo assay shows that
miR-942 overexpressing cells form larger tumors and display higher
tumourigenesis. Furthermore, we demonstrate that miR-942 upregulates the Wnt/beta
catenin signaling activity via directly targeting sFRP4, GSK3beta and TLE1, which
are multiple level negative regulators of the Wnt/beta-catenin signaling cascade.
In addition, our results indicate that c-myc directly binds to the miR-942
promoter and promotes its expression. Taken together, our findings establish an
oncogenic role of miR-942 in ESCC and indicate that miR-942 might be an effective
therapeutic target for ESCC.
PMID- 25844604
TI - Treatment of chronic spontaneous urticaria.
PMID- 25844605
TI - Pollution as a risk factor for the development of melasma and other skin
disorders of facial hyperpigmentation - is there a case to be made?
AB - Worldwide air pollution is a major health concern. There is accumulating
scientific evidence that air pollution plays an important role in extrinsic
aging. This article invites the reader to consider pollution as a possible
emerging etiologic agent for the development of melasma. Pollution may be a risk
factor for melasma and other facial pigmentary dyschromias. Air pollution in the
form of airborne particulate matter (PM) and Polycyclic aromatic hydrocarbons
(PAHs) enter the skin via nanoparticles and generate quinones, which are redox
cycling chemicals that produce reactive oxygen species (ROS). The PM increases
the amount of ROS that triggers the increase of metalloproteinases that leads to
extrinsic aging, which includes skin pigmentation. The incidence of disorders of
facial hyperpigmentation specifically, melasma, is increased in persons of skin
type III-VI living in India and South East Asia. Interestingly, these are also
geographic regions with very heavy pollution. India, South East Asia, China, and
United States lead the world in air pollution.
PMID- 25844606
TI - Cutaneous lupus erythematosus in skin of color.
AB - Cutaneous Lupus Erythematosus (CLE) is a common manifestation in patients with
Systemic Lupus Erythematosus. In a significant population of patients, CLE is the
predominant feature and, in some cases, patients suffer from cutaneous disease
alone. Chronic Cutaneous Lupus Erythematosus (CCLE) is a scarring subtype, more
prevalent in blacks. Patients with skin of color may pose a challenge to
physicians due to exaggerated cutaneous findings and increased risk of post
inflammatory hyperpigmentation and hypertrophic scarring. With the demographics
of the United States rapidly shifting towards a greater population of non
Caucasian racial and ethnic groups, it is imperative that we expand on the
limited research into molecular variation, clinical presentation, and therapeutic
efficacy in CLE. The purpose of this review is to bring attention to the unique
and severe aspects of CLE in persons of color, which calls for early and
aggressive treatment.
PMID- 25844603
TI - Rejuvenating immunity: "anti-aging drug today" eight years later.
AB - The 2014 year ended with celebration: Everolimus, a rapamycin analog, was shown
to improve immunity in old humans, heralding "a turning point" in research and
new era in human quest for immortality. Yet, this turning point was predicted a
decade ago. But what will cause human death, when aging will be abolished?
PMID- 25844607
TI - Efficacy and safety of incobotulinumtoxin A for the correction of glabellar lines
among patients with skin types IV to VI.
AB - BACKGROUND: Despite the frequent use of botulinumtoxin A (BoNTA) in non-Caucasian
patients, safety and efficacy has not been well characterized in persons with
darker skin. OBJECTIVE: To investigate the efficacy and safety of
incobotulinumtoxin A [Xeomin(r) (XEO)] for the correction of glabellar lines
among non-Caucasian patients with Fitzpatrick skin types IV to VI. METHODS: This
open-label, single-center, post-marketing study treated 29 patients with
Fitzpatrick skin types IV to VI with moderate to severe glabellar frown lines.
Evaluation at day 0 included standardized photographs and patient and
investigator assessments. Post evaluation, XEO was administered at 5
intramuscular injection sites with equal aliquots of 4 units per 0.1 mL.
Photographs and assessments were repeated at days 30 and 90. RESULTS: Response to
treatment was defined as a 1 or more point improvement in patient and
investigator assessments. At day 30, 100% (n = 29; 95 C.I. 0.87, 1.00; P< .001)
responded to treatment. At day 90, 69% (n=20; 95% C.I. 0.52, 0.83; P= .42)
responded to treatment. The safety profile was similar to previously reported
trials with BoNTA. CONCLUSION: The efficacy and safety of XEO among patients with
skin types IV to VI is similar to that among persons with fairer skin.
PMID- 25844608
TI - Evaluation of benefit to educational material for photoprotection in those with
cutaneous lupus erythematosus.
AB - BACKGROUND: Photosensitivity (PS) in cutaneous lupus erythematosus (CLE)
contributes to decreased quality of life (QoL). AIMS: We aimed to assess baseline
knowledge about sun protection in persons with CLE and identify knowledge
differences by race. Additionally, we aimed to determine the impact of a verbal
educational intervention on photoprotection and CLE. METHODS: 31 adults with CLE
were recruited from an academic-based dermatology clinic and completed a 17-item
questionnaire about CLE and sun protection at three time points: pre-
intervention (PR-I), post-intervention (PO-I), and 3-month phone follow up (3MF).
An educational intervention using American Academy of Dermatology CLE and sun
protection education materials was delivered between PR-I and PO-I. RESULTS: 31
subjects participated at PR-I and PO-I, and 25 subjects (81%) at 3MF. Baseline
CLE-related PS and photoprotection knowledge differed significantly by race, with
non-Caucasians demonstrating less knowledge (P= 0.049). Knowledge about sun
exposure being linked to lupus increased from 81% to 97% (P=0.25) between PR-I
and PO-I. At PR-I, 19% agreed that smoking was linked to lupus compared to 90% PO
I (P<0.001). There was increased knowledge of lupus risk for non-Caucasians, UV
exposure indoors, and photo-avoidance during peak daytime (P<0.001). CONCLUSION:
There is a baseline disparity in knowledge related to PS and photo protection in
CLE by race. A short educational intervention successfully improved immediate
lupus-related PS and sun exposure knowledge, but knowledge was not retained long
term. It appears educational materials must be improved.
PMID- 25844609
TI - Study of human leukocyte antigen-cw in Egyptian patients with vitiligo.
AB - Human leukocyte antigen (HLA) antigens vary considerably in different racial
groups, and an analysis of results from several geographical locations suggests
that vitiligo appears to be associated with different HLA antigens in different
groups. The aim of this work was to assess the association of HLA-Cw with
vitiligo in the Egyptian population. Forty unrelated patients with nonsegmental
vitiligo and 20 matched controls were selected. A polymerase chain reaction
sequence specific primer (PCR-SSP) method was used to determine HLA DNA typing.
There was a statistically significant difference in the association of HLA-Cw6
with vitiligo in the 2 studied groups. A comparatively increased number of
patients showed HLA-Cw2 and HLA-Cw7 (13.64%). However, there were no
statistically significant differences. To the best of our knowledge, this is the
first molecular study of HLA typing in Egyptian patients with vitiligo. Our
findings are in agreement with earlier studies that reported statistically
increased frequencies for allele of HLA-Cw6 in Northern Italian, Kuwaiti, Chinese
Han, and Saudi populations (45.45%, P<.05).
PMID- 25844610
TI - Quantifying the impact cosmetic make-up has on age perception and the first
impression projected.
AB - INTRODUCTION: First impressions are lasting, consequential and defined as the
immediate judgment made of another from zero acquaintance. Multiple studies have
reported the benefits of cosmetic make-up. We set out to investigate the
psychosocial and aesthetic effects of cosmetic make-up in order to better
understand why women wear it. MATERIALS AND METHODS: Twenty-seven women were
recruited in order to examine the effects of cosmetic make-up on first
impressions. The photographs of individual subjects wearing the control
cosmetics, their own make-up, and no make-up were randomly assigned to three
binders (A, B, and C). Three hundred evaluators participated (100 evaluators per
book) and completed a 10-point First Impression Scale for each of the 27 photos
in their binder. RESULTS: Statistical analysis of the collected data was
conducted in SPSS using two-tailed t-tests to determine the statistical
significance of the differences between first impressions of Own Make-up vs No
Make-up, No Make-up vs Control Make-up, and Own Makeup vs Control Make-up. There
was a significant difference in improvement in all pairings across all 8
categories in the First Impressions questionnaire particularly in perceived age
between own make-up, no make-up, control make-up (41, 42, 38; P<0.001).
DISCUSSION: Our study evaluated the first impressions, age perception, self
esteem, and the quality of life impact that cosmetic makeup has on women's
appearance and confidence. Subjects wearing cosmetic make-up appeared 4 years
younger than those wearing no make-up. And the control cosmetic make-up subjects
on average projected a 37% better first impression than subjects wearing no make
up. We objectively quantified and qualified the benefits of applying cosmetic
make-up. Make-up can reduce the perceived age, improve the first impression
projected and increase the self-esteem of those who apply it.
PMID- 25844611
TI - A novel patient support program to address isotretinoin adherence: proof-of
concept analysis.
AB - The iPLEDGE protocol for isotretinoin treatment requires multiple steps to be
completed within strict timing windows, resulting in many interruptions or
discontinuations of treatment. The US Food and Drug Administration has indicated
that approximately 40% of isotretinoin prescriptions written over the course of
one year of the iPLEDGE program were denied due to failure to comply with
iPLEDGE. Insurance restrictions add to the likelihood of prescriptions not being
filled. Here, we describe a novel program implemented specifically to assist
patients and providers with improving isotretinoin therapy adherence. This
innovative isotretinoin support program provides assistance with insurance
questions and hurdles, an uninterrupted treatment supply, educational support,
reminder communications, and an indigent patient assistance program. Proof-of
concept analysis shows that 17 months after implementation of the program, 93% of
prescriptions received have been filled. Utilization of the program appears to
improve adherence to an isotretinoin treatment regimen, with fewer interruptions
due directly to unfilled prescriptions.
PMID- 25844612
TI - The efficacy and tolerability of a fixed combination clindamycin (1.2%) and
benzoyl peroxide (3.75%) aqueous gel in patients with facial acne vulgaris:
gender as a clinically relevant outcome variable.
AB - OBJECTIVE: To investigate whether treatment differences exist in male and female
patients with moderate to severe acne treated with clindamycin phosphate 1.2%/BP
3.75% gel or vehicle as monotherapy. METHODS: A post hoc analysis comparing the
efficacy and cutaneous tolerability in 498 male and female patients with moderate
to severe acne receiving clindamycin phosphate 1.2%/BP 3.75% gel, or vehicle for
12 weeks. RESULTS: The efficacy of clindamycin phosphate 1.2%/BP 3.75% gel was
greater than vehicle (P>.001) in both genders. Within the clindamycin phosphate
1.2%/BP 3.75% gel group, the mean percent change from baseline in inflammatory
and noninflammatory lesion counts was greater among females than males, as was
the percentage of subjects who achieved a 2-grade reduction in the EGSS (P=.049).
LIMITATIONS: It is not possible to determine the contributions of the individual
active ingredients. CONCLUSIONS: Clindamycin phosphate 1.2%/BP 3.75% gel provides
statistically significant greater efficacy than vehicle with a favorable safety
and tolerability profile. It appears to be more effective in female patients.
PMID- 25844613
TI - A method for maintaining the clinical results of 4% hydroquinone and 0.025%
tretinoin with a cosmeceutical formulation.
AB - Facial dyspigmentation treatment is an unmet need in dermatology with increasing
challenges due to the questionable safety of hydroquinone. This research examined
a new OTC formulation containing hydroxyphenoxy propionic acid, ellagic acid,
yeast extract, and salicylic acid on subjects who previously completed 12 weeks
of treatment with 4% hydroquinone and 0.025% retinoic acid. The goal of this
study was to evaluate the skin lightening and tolerability profile of a 20-week
maintanence therapy with a cosmeceutical formulation during the summer months. 33
healthy subjects ages 25-60 years with moderate facial dyspigmentation defined as
a score of 3 on a 5-point scale were enrolled. There was statistically
significant improvement at week 20 in terms of even skin tone (P<0.001), spot
intensity (P<0.001), spot size (P<0.05) and overall hyperpigmentation (P>=0.002).
PMID- 25844614
TI - Evaluation of a novel home skin care platform.
AB - The home beauty device market is rapidly growing, having more than tripled in the
last four years. This study evaluates several specific attachment heads using a
novel home skincare platform (HSP). By incorporating multiple treatment heads for
cleansing, skin smoothing, and skin infusion, this device has the potential to
address many potential treatment goals. The first subset of this study is a
blinded, randomized split-face study evaluating the efficacy of the HSP device
with a standard brush head for make-up removal and compares the HSP device to a
currently marketed home cleansing device. The results show that the HSP cleansing
head was comparable to the leading home skin cleansing device on the market. The
HSP's skin smoothing head showed statistically significant improvement in
erythema and dryness over baseline levels with significant histologic changes
including normalization of epidermal thickness in only 10 days of use. This is
comparable to and exceeds many well-studied antiaging treatments after weeks and
months of therapy. Finally, the infusion head demonstrated improvement in skin
hydration over baseline levels.
PMID- 25844615
TI - Assessment of the safety and efficacy of topical copper chlorophyllin in women
with photodamaged facial skin.
AB - BACKGROUND: Chronic exposure to the sun causes the skin to prematurely age.
Photodamaged skin is characterized by progressive damage to the dermal
extracellular matrix with loss of collagen and degradation of elastin. Clinical
manifestations of such photoaged or photodamaged skin include wrinkles and
irregular pigmentation. Various cosmetic treatments including topical retinoids,
growth factors, and skin lighteners have shown some benefit. Salts of copper
chlorophyllin complex are semi-synthetic naturally derived compounds with anti
oxidant and wound healing activity that has not been previously tested in
photodamaged skin. OBJECTIVES: This single-center pilot study was conducted to
assess the efficacy and safety of a liposomal dispersion of topically applied
sodium copper chlorophyllin complex in women with mild-moderate fine lines and
wrinkles in the periocular areas and facial solar lentigenes over a course of 8
weeks. METHODS: Subjects were supplied with the test product, a topical gel
containing chlorophyllin complex salts (0.066%), with directions to apply a pea
sized amount to the periocular areas, cheeks and nose every morning and evening.
Clinical assessments were performed at screening/baseline and at week 8.
Standardized digital photographs were taken and self-assessment questionnaires
were conducted. RESULTS: Ten subjects completed the 8-week study. All clinical
efficacy parameters showed statistically significant improvements over baseline
at week 8. The study product was well tolerated. Subject questionnaires showed
the test product was highly rated. CONCLUSIONS: In this pilot study, a topical
formulation containing a liposomal dispersion of sodium copper chlorophyllin
complex was shown to be clinically effective and well tolerated for the treatment
of mild-moderate photodamage and solar lentigenes when used for 8 weeks.
PMID- 25844616
TI - Reduced appearance of under-eye bags with twice-daily application of epidermal
growth factor (EGF) serum: a pilot study.
AB - BACKGROUND: Under-eye bags are a common manifestation of age and a frequent
complaint among patients who no longer feel youthful. Non-invasive topical agents
are largely ineffective at reducing their appearance. OBJECTIVE: We studied the
ability of a topical serum containing epidermal growth factor (EGF) to minimize
the appearance of under-eye bags. METHODS: A single-center clinical trial was
performed on eighteen volunteer male and female patients with under-eye bags.
Subjects applied EGF serum to the infraorbital area twice daily for 12 weeks. At
each visit, subjects were evaluated using clinical photography and written self
assessment. A grade on the Merz Infraorbital Hollowness Scale was also given and
two independent, blind investigators assigned an Investigator's Global Assessment
(IGA) score. At the trial's end, patients shared their final evaluation and
perception of results with a questionnaire. RESULTS: Sixteen subjects completed
the trial. The final average Merz grade was 1.63 (SEM = .273), statistically
significantly lower than the mean baseline average of 2.06 (SEM = .232) (P =
.0019). A reduction in average IGA score was also significant (P< .0001). Average
initial IGA was 2.75 (SEM = .270) and average final IGA was 2.00 (SEM = .310).
All but two subjects reported improvement at the final visit. Improvement was
quantified as 76-100% by two subjects, 50-75% by three subjects, and 25-49% by
nine subjects. Eleven subjects classified their under-eye bags as milder at the
end of the trial compared to the first visit. Seven subjects reported greater
satisfaction with their overall facial appearance. Of the subjects who had used
other topical treatments in the past, two reported the serum to be "significantly
better" and four said it was "better" in treating their under-eye bags.
CONCLUSION: Our results offer evidence that topical EGF can reduce the appearance
of under-eye bags.
PMID- 25844617
TI - Minocycline pigmentation following carbon dioxide laser resurfacing: treatment
with the Q-switched Nd:YAG laser.
AB - Minocycline is among the most common drugs to cause drug-induced pigmentation.
Dermal deposition of drug metabolites typically occurs in areas of vascular
leakage, such as surrounding lower extremity spider veins, within erythema
associated with solar elastosis, and in areas of bruising. The skin affected by
minocycline pigmentation typically takes on a slate-gray coloring in affected
areas. The current patient developed minocycline pigmentation after carbon
dioxide laser resurfacing of her upper lip to treat rhytides in the laser-treated
area. Laser treatment with the 1,064 nm, Q-switched Nd:YAG laser was able to
remove the pigmentation.
PMID- 25844618
TI - IL-17A Is Elevated in End-Stage Chronic Obstructive Pulmonary Disease and
Contributes to Cigarette Smoke-induced Lymphoid Neogenesis.
AB - RATIONALE: End-stage chronic obstructive pulmonary disease (COPD) is associated
with an accumulation of pulmonary lymphoid follicles. IL-17A is implicated in
COPD and pulmonary lymphoid neogenesis in response to microbial stimuli. We
hypothesized that IL-17A is increased in peripheral lung tissue during end-stage
COPD and also directly contributes to cigarette smoke-induced lymphoid
neogenesis. OBJECTIVES: To characterize the tissue expression and functional role
of IL-17A in end-stage COPD. METHODS: Automated immune detection of IL-17A and IL
17F was performed in lung tissue specimens collected from patients with Global
Initiative for Chronic Obstructive Lung Disease stage I-IV COPD, and smoking and
never-smoking control subjects. In parallel, Il17a(-/-) mice and wild-type
control animals were exposed to cigarette smoke for 24 weeks, and pulmonary
lymphoid neogenesis was assessed. MEASUREMENTS AND MAIN RESULTS: Tissue
expression of IL-17A and IL-17F was increased in COPD and correlated with lung
function decline. IL-17A was significantly elevated in severe to very severe COPD
(Global Initiative for Chronic Obstructive Lung Disease III/IV) compared with
both smokers and never-smokers without COPD. Although CD3(+) T cells expressed IL
17A in very severe COPD, most IL-17A(+) cells were identified as tryptase
positive mast cells. Attenuated lymphoid neogenesis and reduced expression of the
B-cell attracting chemokine C-X-C motif ligand (CXCL) 12 was observed in
cigarette smoke-exposed Il17a(-/-) mice. CXCL12 was also highly expressed in
lymphoid follicles in COPD lungs, and the pulmonary expression was significantly
elevated in end-stage COPD. CONCLUSIONS: IL-17A in the peripheral lung of
patients with severe to very severe COPD may contribute to disease progression
and development of lymphoid follicles via activation of CXCL12.
PMID- 25844619
TI - The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults.
AB - CONTEXT: It has been assumed that the increase in urine calcium (Ca) that
accompanies an increase in dietary protein was due to increased bone resorption.
However, studies using stable Ca isotopes have found that dietary protein
increases Ca absorption without increasing bone resorption. OBJECTIVE: The
objective of the study was to investigate the impact of a moderately high protein
diet on bone mineral density (BMD). DESIGN: This was a randomized, double-blind,
placebo-controlled trial of protein supplementation daily for 18 months. SETTING:
The study was conducted at two institutional research centers. PARTICIPANTS: Two
hundred eight older women and men with a body mass index between 19 and 32
kg/m(2) and a self-reported protein intake between 0.6 and 1.0 g/kg participated
in the study. INTERVENTION: Subjects were asked to incorporate either a 45-g whey
protein or isocaloric maltodextrin supplement into their usual diet for 18
months. MAIN OUTCOME MEASURE: BMD by dual-energy x-ray absorptiometry, body
composition, and markers of skeletal and mineral metabolism were measured at
baseline and at 9 and 18 months. RESULTS: There were no significant differences
between groups for changes in L-spine BMD (primary outcome) or the other skeletal
sites of interest. Truncal lean mass was significantly higher in the protein
group at 18 months (P = .048). C-terminal telopeptide (P = .0414), IGF-1 (P =
.0054), and urinary urea (P < .001) were also higher in the protein group at the
end of the study period. There was no difference in estimated glomerular
filtration rate at 18 months. CONCLUSION: Our data suggest that protein
supplementation above the recommended dietary allowance (0.8 g/kg) may preserve
fat-free mass without adversely affecting skeletal health or renal function in
healthy older adults.
PMID- 25844621
TI - Correction to Survey of polyphenol constituents in grapes and grape-derived
products.
PMID- 25844620
TI - Adrenal Insufficiency in Corticosteroids Use: Systematic Review and Meta
Analysis.
AB - OBJECTIVE: We aimed to estimate pooled percentages of patients with adrenal
insufficiency after treatment with corticosteroids for various conditions in a
meta-analysis. Secondly, we aimed to stratify the results by route of
administration, disease, treatment dose, and duration. METHODS: We searched seven
electronic databases (PubMed, MEDLINE, EMBASE, COCHRANE, CENTRAL, Web of Science,
and CINAHL/Academic Search Premier) in February 2014 to identify potentially
relevant studies. Original articles testing adult corticosteroid users for
adrenal insufficiency were eligible. RESULTS: We included 74 articles with a
total of 3753 participants. Stratified by administration form, percentages of
patients with adrenal insufficiency ranged from 4.2% for nasal administration
(95% confidence interval [CI], 0.5-28.9) to 52.2% for intra-articular
administration (95% CI, 40.5-63.6). Stratified by disease, percentages ranged
from 6.8% for asthma with inhalation corticosteroids only (95% CI, 3.8-12.0) to
60.0% for hematological malignancies (95% CI, 38.0-78.6). The risk also varied
according to dose from 2.4% (95% CI, 0.6-9.3) (low dose) to 21.5% (95% CI, 12.0
35.5) (high dose), and according to treatment duration from 1.4% (95% CI, 0.3
7.4) (<28 d) to 27.4% (95% CI, 17.7-39.8) (>1 year) in asthma patients.
CONCLUSIONS: 1) Adrenal insufficiency after discontinuation of glucocorticoid
occurs frequently; 2) there is no administration form, dosing, treatment
duration, or underlying disease for which adrenal insufficiency can be excluded
with certainty, although higher dose and longer use give the highest risk; 3) the
threshold to test corticosteroid users for adrenal insufficiency should be low in
clinical practice, especially for those patients with nonspecific symptoms after
cessation.
PMID- 25844622
TI - Object-based attention in real-world scenes.
AB - We are continually confronted with more visual information than we can process in
a given moment. In order to interact effectively with our environment,
attentional mechanisms are used to select subsets of environmental properties for
enhanced processing. Previous research demonstrated that spatial regions can be
selected based on either their low-level feature or high-level semantic
properties. However, the efficiency with which we interact with the world
suggests that there must be an additional, midlevel, factor constraining
effective attentional space. The present study investigates whether object-based
attentional selection is one such midlevel factor that constrains visual
attention in complex, real-world scenes. Participants viewed scene images while
their eye movements were recorded. During viewing, a cue appeared on an object
which participants were instructed to fixate. A target then appeared either on
the same object as the cue, on a different object, or floating. Participants
initiated saccades faster and had shorter response times to targets presented on
the same object as the fixated cue. The results strongly suggest that when
attending to a location on an object, the entire object benefits perceptually.
This object-based effect on the distribution of spatial attention forms a
critical link between low- and high-level factors that direct attention
efficiently in complex real-world scenes.
PMID- 25844623
TI - A change of task prolongs early processes: evidence from ERPs in lexical tasks.
AB - Switching tasks costs time. Allowing time to prepare reduces the cost, but
usually leaves an irreducible "residual cost." Most accounts of this residual
cost locate it within the response-selection stage of processing. To determine
which processing stage is affected, we measured event-related potentials (ERPs)
as participants performed a reading task or a perceptual judgment task, and
examined the effect of a task switch on early markers of lexical processing. A
task cue preceding a string of blue and red letters instructed the participant
either to read the letter string (for a semantic classification in Experiment 1,
and a lexical decision in Experiment 2) or to judge the symmetry of its color
pattern. In Experiment 1, having to switch to the reading task delayed the
evolution of the effect of word frequency on the reading task ERP by a
substantial fraction of the effect on reaction time (RT). In Experiment 2, a task
switch delayed the onset of the effect of lexical status on the ERP by about the
same extent that it prolonged the RT. These effects indicate an early locus of
(most of) the residual switch cost: We propose that this reflects a form of task
related attentional inertia. Other findings have implications for the
automaticity of lexical access: Effects of frequency, lexicality, and
orthographic familiarity on ERPs in the symmetry task indicated involuntary, but
attenuated, orthographic and lexical processing even when attention was focused
on a nonlexical property.
PMID- 25844624
TI - Individual differences in ensemble perception reveal multiple, independent levels
of ensemble representation.
AB - Ensemble perception, including the ability to "see the average" from a group of
items, operates in numerous feature domains (size, orientation, speed, facial
expression, etc.). Although the ubiquity of ensemble representations is well
established, the large-scale cognitive architecture of this process remains
poorly defined. We address this using an individual differences approach. In a
series of experiments, observers saw groups of objects and reported either a
single item from the group or the average of the entire group. High-level
ensemble representations (e.g., average facial expression) showed complete
independence from low-level ensemble representations (e.g., average orientation).
In contrast, low-level ensemble representations (e.g., orientation and color)
were correlated with each other, but not with high-level ensemble representations
(e.g., facial expression and person identity). These results suggest that there
is not a single domain-general ensemble mechanism, and that the relationship
among various ensemble representations depends on how proximal they are in
representational space.
PMID- 25844625
TI - Text exposure predicts spoken production of complex sentences in 8- and 12-year
old children and adults.
AB - There is still much debate about the nature of the experiential and maturational
changes that take place during childhood to bring about the sophisticated
language abilities of an adult. The present study investigated text exposure as a
possible source of linguistic experience that plays a role in the development of
adult-like language abilities. Corpus analyses of object and passive relative
clauses (Object: The book that the woman carried; Passive: The book that was
carried by the woman) established the frequencies of these sentence types in
child-directed speech and children's literature. We found that relative clauses
of either type were more frequent in the written corpus, and that the ratio of
passive to object relatives was much higher in the written corpus as well. This
analysis suggests that passive relative clauses are much more frequent in a
child's linguistic environment if they have high rates of text exposure. We then
elicited object and passive relative clauses using a picture-description
production task with 8- and 12-year-old children and adults. Both group and
individual differences were consistent with the corpus analyses, such that older
individuals and individuals with more text exposure produced more passive
relative clauses. These findings suggest that the qualitatively different
patterns of text versus speech may be an important source of linguistic
experience for the development of adult-like language behavior.
PMID- 25844626
TI - Flash fire and slow burn: women's cardiovascular reactivity and recovery
following hostile and benevolent sexism.
AB - Women's cardiovascular responses to sexist treatment are documented, but
researchers have yet to consider these responses separately as a function of
sexism type (hostile vs. benevolent). This study demonstrates distinct effects of
hostile and benevolent sexism for women's cardiovascular responses that indicate
increased risk for cardiovascular disease. Female participants performed a
demanding insight task after exposure to a male researcher who offered them a
hostilely sexist, benevolently sexist, or nonsexist comment. Women displayed
heightened cardiovascular reactivity (increases from baseline) during the task
following hostile sexism, and they displayed impaired cardiovascular recovery
(return to baseline after the task) following benevolent sexism. The effects seen
in the hostile condition were mediated by self-reported anger. These findings
indicate that women's affective responses to hostile and benevolent sexism differ
but that exposure to both forms of sexism may have negative cardiovascular
consequences.
PMID- 25844627
TI - Dynamics of postdecisional processing of confidence.
AB - Most cognitive theories assume that confidence and choice happen simultaneously
and are based on the same information. The 3 studies presented in this article
instead show that confidence judgments can arise, at least in part, from a
postdecisional evidence accumulation process. As a result of this process,
increasing the time between making a choice and confidence judgment improves
confidence resolution. This finding contradicts the notion that confidence
judgments are biased by decision makers seeking confirmatory evidence. Further
analysis reveals that the improved resolution is due to a reduction in confidence
in incorrect responses, while confidence in correct responses remains relatively
constant. These results are modeled with a sequential sampling process that
allows evidence accumulation to continue after a choice is made and maps the
amount of accumulated evidence onto a confidence rating. The cognitive modeling
analysis reveals that the rate of evidence accumulation following a choice does
slow relative to the rate preceding choice. The analysis also shows that the
asymmetry between confidence in correct and incorrect choices is compatible with
state-dependent decay in the accumulated evidence: Evidence consistent with the
current state results in a deceleration of accumulated evidence and consequently
evidence appears to have a decreasing impact on observed confidence. In contrast,
evidence inconsistent with the current state results in an acceleration of
accumulated evidence toward the opposite direction and consequently evidence
appears to have an increasing impact on confidence. Taken together, this process
level understanding of confidence suggests a simple strategy for improving
confidence accuracy: take a bit more time to make confidence judgments.
PMID- 25844628
TI - Disfluent fonts don't help people solve math problems.
AB - Prior research suggests that reducing font clarity can cause people to consider
printed information more carefully. The most famous demonstration showed that
participants were more likely to solve counterintuitive math problems when they
were printed in hard-to-read font. However, after pooling data from that
experiment with 16 attempts to replicate it, we find no effect on solution rates.
We examine potential moderating variables, including cognitive ability,
presentation format, and experimental setting, but we find no evidence of a
disfluent font benefit under any conditions. More generally, though disfluent
fonts slightly increase response times, we find little evidence that they
activate analytic reasoning.
PMID- 25844629
TI - Confidence intervals for distinguishing ordinal and disordinal interactions in
multiple regression.
AB - Distinguishing between ordinal and disordinal interaction in multiple regression
is useful in testing many interesting theoretical hypotheses. Because the
distinction is made based on the location of a crossover point of 2 simple
regression lines, confidence intervals of the crossover point can be used to
distinguish ordinal and disordinal interactions. This study examined 2 factors
that need to be considered in constructing confidence intervals of the crossover
point: (a) the assumption about the sampling distribution of the crossover point,
and (b) the possibility of abnormally wide confidence intervals for the crossover
point. A Monte Carlo simulation study was conducted to compare 6 different
methods for constructing confidence intervals of the crossover point in terms of
the coverage rate, the proportion of true values that fall to the left or right
of the confidence intervals, and the average width of the confidence intervals.
The methods include the reparameterization, delta, Fieller, basic bootstrap,
percentile bootstrap, and bias-corrected accelerated bootstrap methods. The
results of our Monte Carlo simulation study suggest that statistical inference
using confidence intervals to distinguish ordinal and disordinal interaction
requires sample sizes more than 500 to be able to provide sufficiently narrow
confidence intervals to identify the location of the crossover point.
PMID- 25844630
TI - Advancing theory and practice through collaborative research in environmental
gerontology.
PMID- 25844631
TI - Effects of caffeine and its metabolite paraxanthine on intracranial self
stimulation in male rats.
AB - Caffeine is the most widely used psychostimulant in the world, though preclinical
studies suggest weaker evidence for abuse-related effects than stimulants with
high abuse liability, such as amphetamine or cocaine. Intracranial self
stimulation (ICSS) is 1 procedure used to assess the abuse liability of drugs,
and previous studies have produced mixed results regarding whether caffeine
produces an abuse-related facilitation of ICSS. This study assessed both caffeine
and its main metabolite in humans, paraxanthine, using a frequency-rate ICSS
procedure and compared their effects to those of amphetamine and cocaine. Male
Sprague-Dawley rats were implanted with intracranial electrodes targeting the
medial forebrain bundle and trained to respond under a fixed-ratio 1 schedule for
brain stimulation that varied across a range of frequencies (56-158 Hz in 0.05
log increments). Data analysis focused on 3 dependent measures: reinforced
responding (defined as responses that produced brain stimulation), nonreinforced
responding (defined as responses that occurred during each 0.5 s brain
stimulation and that did not produce additional stimulation), and total
responding (reinforced plus nonreinforced responding). Both amphetamine and
cocaine produced robust increases in total, reinforced, and nonreinforced
responses. Caffeine also increased total, reinforced, and nonreinforced
responses, but the caffeine dose-effect curve had an inverted-U shape, and peak
ICSS facilitation was less than that produced by amphetamine or cocaine.
Paraxanthine increased only total responses and nonreinforced responses. These
results suggest that paraxanthine has low abuse liability and does not mediate
abuse-related effects of caffeine.
PMID- 25844633
TI - Mapping the BH3 Binding Interface of Bcl-xL, Bcl-2, and Mcl-1 Using Split
Luciferase Reassembly.
AB - The recognition of helical BH3 domains by Bcl-2 homology (BH) receptors plays a
central role in apoptosis. The residues that determine specificity or promiscuity
in this interactome are difficult to predict from structural and computational
data. Using a cell free split-luciferase system, we have generated a 276 pairwise
interaction map for 12 alanine mutations at the binding interface for three
receptors, Bcl-xL, Bcl-2, and Mcl-1, and interrogated them against BH3 helices
derived from Bad, Bak, Bid, Bik, Bim, Bmf, Hrk, and Puma. This panel, in
conjunction with previous structural and functional studies, starts to provide a
more comprehensive portrait of this interactome, explains promiscuity, and
uncovers surprising details; for example, the Bcl-xL R139A mutation disrupts
binding to all helices but the Bad-BH3 peptide, and Mcl-1 binding is particularly
perturbed by only four mutations of the 12 tested (V220A, N260A, R263A, and
F319A), while Bcl-xL and Bcl-2 have a more diverse set of important residues
depending on the bound helix.
PMID- 25844634
TI - Ultraclean patterned transfer of single-layer graphene by recyclable pressure
sensitive adhesive films.
AB - We report an ultraclean, cost-effective, and easily scalable method of
transferring and patterning large-area graphene using pressure sensitive adhesive
films (PSAFs) at room temperature. This simple transfer is enabled by the
difference in wettability and adhesion energy of graphene with respect to PSAF
and a target substrate. The PSAF-transferred graphene is found to be free from
residues and shows excellent charge carrier mobility as high as ~17,700 cm(2)/V.s
with less doping compared to the graphene transferred by thermal release tape
(TRT) or poly(methyl methacrylate) (PMMA) as well as good uniformity over large
areas. In addition, the sheet resistance of graphene transferred by recycled PSAF
does not change considerably up to 4 times, which would be advantageous for more
cost-effective and environmentally friendly production of large-area graphene
films for practical applications.
PMID- 25844632
TI - Modeling naturalistic craving, withdrawal, and affect during early nicotine
abstinence: A pilot ecological momentary assessment study.
AB - Despite the critical role of withdrawal, craving, and positive affect (PA) and
negative affect (NA) in smoking relapse, relatively little is known about the
temporal and predictive relationship between these constructs within the first
day of abstinence. This pilot study aims to characterize dynamic changes in
withdrawal, craving, and affect over the course of early abstinence using
ecological momentary assessment. Beginning immediately after smoking, moderate
and heavy smoking participants (n = 15 per group) responded to hourly surveys
assessing craving, withdrawal, NA, and PA. Univariate and multivariate multilevel
random coefficient modeling was used to describe the progression of craving,
withdrawal/NA, and PA and to test correlations between these constructs at the
subject level over the course of early abstinence. Heavy smokers reported greater
craving from 1-4 hr of abstinence and greater withdrawal/NA after 3 or more hours
as compared with moderate smokers. Level of withdrawal/NA was strongly positively
associated with craving, and PA was negatively correlated with craving; however,
the temporal dynamics of these correlations differed substantially. The
association between withdrawal/NA and craving decreased over early abstinence,
whereas the reverse was observed for PA. These findings can inform experimental
studies of nicotine abstinence as well as their clinical applications to smoking
cessation efforts. In particular, these results help to elucidate the role of PA
in nicotine abstinence by demonstrating its independent association with nicotine
craving over and above withdrawal/NA. If supported by future studies, these
findings can refine experimental methods and clinical approaches for smoking
cessation.
PMID- 25844635
TI - o-Boronato- and o-Trifluoroborato-Phosphonium Salts Supported by L-alpha-Amino
Acid Side Chain.
AB - The synthesis of o-boronato- and o-trifluoroborato-phosphonium salts supported by
the L-amino acid side chain is described. The synthesis of these new class of
amino acid derivatives was achieved by stereoselective quaternization of o
(pinacolato)boronatophenylphosphine with beta- or gamma-iodo amino acid
derivatives which are prepared from L-serine or L-aspartic acid, respectively.
The quaternization of the phosphine was performed using either iodo amino ester
or carboxylic acid derivatives. In addition, free carboxylic acid and amine
derivatives were obtained by saponification or HCl acidolysis of o-boronato
phosphonium amino esters, respectively. The usefulness of these compounds in
peptide coupling was demonstrated by coupling an o-boronato-phosphonium amino
ester with an aspartic acid moiety. When the o-boronato-phosphonium amino acid or
dipeptide derivatives were mixed with fluoride, the corresponding o
trifluoroborated products were cleanly and rapidly obtained in high isolated
yields. The hydrolysis of these compounds at room temperature using a phosphate
buffer pH 7/CD3CN mixture has shown only traces of free fluoride F(-) after
several days. Finally, a preliminary radiolabeling essay has proven the facile
[(18)F]-fluoride incorporation and high stability of the radiolabeled product in
aqueous conditions. Indeed, this new class of boron-phosphonium amino acid
derivatives shows promising properties for their applications in synthesis and
labeling of peptides.
PMID- 25844636
TI - Bexarotene reduces blood-brain barrier permeability in cerebral ischemia
reperfusion injured rats.
AB - BACKGROUND: Matrix metalloproteinase-9 (MMP-9) over-expression disrupts the blood
brain barrier (BBB) in the ischemic brain. The retinoid X receptor agonist
bexarotene suppresses MMP-9 expression in endothelial cells and displays
neuroprotective effects. Therefore, we hypothesized that bexarotene may have a
beneficial effect on I/R-induced BBB dysfunction. METHODS: A total of 180 rats
were randomized into three groups (n = 60 each): (i) a sham-operation group, (ii)
a cerebral ischemia-reperfusion (I/R) group, and (iii) an I/R+bexarotene group.
Brain water content was measured by the dry wet weight method. BBB permeability
was analyzed by Evans Blue staining and the magnetic resonance imaging contrast
agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were
assessed by reverse transcription polymerase chain reaction, Western blotting,
and gelatin zymography, respectively. Apolipoprotein E (apoE), claudin-5, and
occludin expression were analyzed by Western blotting. RESULTS: After 24 h, 48 h,
and 72 h post-I/R, several effects were observed with bexarotene administration:
(i) brain water content and BBB permeability were significantly reduced; (ii) MMP
9 mRNA and protein expression as well as activity were significantly decreased;
(iii) claudin-5 and occludin expression were significantly increased; and (iv)
apoE expression was significantly increased. CONCLUSIONS: Bexarotene decreases
BBB permeability in rats with cerebral I/R injury. This effect may be due in part
to bexarotene's upregulation of apoE expression, which has been previously shown
to reduce BBB permeability through suppressing MMP-9-mediated degradation of the
tight junction proteins claudin-5 and occludin. This work offers insight to aid
future development of therapeutic agents for cerebral I/R injury in human
patients.
PMID- 25844637
TI - Intrinsic photocatalytic assessment of reactively sputtered TiO2 films.
AB - Thin TiO2 films were prepared by DC magnetron reactive sputtering at different
oxygen partial pressures. Depending on the oxygen partial pressure during
sputtering, a transition from metallic Ti to TiO2 was identified by spectroscopic
ellipsometry. The crystalline nature of the film developed during a subsequent
annealing step, resulting in thin anatase TiO2 layers, displaying photocatalytic
activity. The intrinsic photocatalytic activity of the catalysts was evaluated
for the degradation of methylene blue (MB) using a microfluidic reactor. A
numerical model was employed to extract the intrinsic reaction rate constants.
High conversion rates (90% degradation within 20 s residence time) were observed
within these microreactors because of the efficient mass transport and light
distribution. To evaluate the intrinsic reaction kinetics, we argue that mass
transport has to be accounted for. The obtained surface reaction rate constants
demonstrate very high reactivity for the sputtered TiO2 films. Only for the
thinnest film, 9 nm, slightly lower kinetics were observed.
PMID- 25844638
TI - Improving executive functioning in children with ADHD: training multiple
executive functions within the context of a computer game. a randomized double
blind placebo controlled trial.
AB - INTRODUCTION: Executive functions (EFs) training interventions aimed at ADHD
symptom reduction have yielded mixed results. Generally, these interventions
focus on training a single cognitive domain (e.g., working memory [WM],
inhibition, or cognitive-flexibility). However, evidence suggests that most
children with ADHD show deficits on multiple EFs, and that these EFs are largely
related to different brain regions. Therefore, training multiple EFs might be a
potentially more effective strategy to reduce EF-related ADHD symptoms. METHODS:
Eighty-nine children with a clinical diagnosis of ADHD (aged 8-12) were
randomized to either a full-active-condition where visuospatial WM, inhibition
and cognitive-flexibility were trained, a partially-active-condition where
inhibition and cognitive-flexibility were trained and the WM-training task was
presented in placebo-mode, or to a full placebo-condition. Short-term and long
term (3-months) effects of this gamified, 25-session, home-based computer
training were evaluated on multiple outcome domains. RESULTS: During training
compliance was high (only 3% failed to meet compliance criteria). After training,
only children in the full-active condition showed improvement on measures of
visuospatial short-term-memory (STM) and WM. Inhibitory performance and
interference control only improved in the full-active- and the partially-active
condition. No Treatment-condition x Time interactions were found for cognitive
flexibility, verbal WM, complex-reasoning, nor for any parent-, teacher-, or
child-rated ADHD behaviors, EF-behaviors, motivational behaviors, or general
problem behaviors. Nonetheless, almost all measures showed main Time-effects,
including the teacher-ratings. CONCLUSIONS: Improvements on inhibition and
visuospatial STM and WM were specifically related to the type of treatment
received. However, transfer to untrained EFs and behaviors was mostly nonspecific
(i.e., only interference control improved exclusively in the two EF training
conditions). As such, in this multiple EF-training, mainly nonspecific treatment
factors - as opposed to the specific effects of training EFs-seem related to far
transfer effects found on EF and behavior. TRIAL REGISTRATION: trialregister.nl
NTR2728. Registry name: improving executive functioning in children with ADHD:
training executive functions within the context of a computer game; registry
number: NTR2728.
PMID- 25844639
TI - UV-Induced DNA Interstrand Cross-Linking and Direct Strand Breaks from a New Type
of Binitroimidazole Analogue.
AB - Four novel photoactivated binitroimidazole prodrugs were synthesized. These
agents produced DNA interstrand cross-links (ICLs) and direct strand breaks (DSB)
upon UV irradiation, whereas no or very few DNA ICLs and DSBs were observed
without UV treatment. Although these four molecules (1-4) contain the same
binitroimidazole moiety, they bear four different leaving groups, which resulted
in their producing different yields of DNA damage. Compound 4, with nitrogen
mustard as a leaving group, showed the highest ICL yield. Surprisingly, compounds
1-3, without any alkylating functional group, also induced DNA ICL formation,
although they did so with lower yields, which suggested that the binitroimidazole
moiety released from UV irradiation of 1-3 is capable of cross-linking DNA. The
DNA cross-linked products induced by these compounds were completely destroyed
upon 1.0 M piperidine treatment at 90 degrees C (leading to cleavage at dG
sites), which revealed that DNA cross-linking mainly occurred via alkylation of
dGs. We proposed a possible mechanism by which alkylating agents were released
from these compounds. HRMS and NMR analysis confirmed that free nitrogen mustards
were generated by UV irradiation of 4. Suppression of DNA ICL and DSB formation
by a radical trap, TEMPO, indicated the involvement of free radicals in the photo
reactions of 3 and 4 with DNA. On the basis of these data, we propose that UV
irradiation of compounds 1-4 generated a binitroimidazole intermediate that cross
links DNA. The higher ICL yield observed with 4 resulted from the amine effector
nitrogen mustard released from UV irradiation.
PMID- 25844640
TI - Gas-solid reaction kinetics of ZnFe2O4 formation from 907 to 1100 degrees C.
AB - The reaction kinetics of Zn vapor with Fe3O4 (magnetite) were studied from 907 to
1100 degrees C using a new experimental setup that only allows contact between
the reactants through a gas-solid reaction. Hematite was used to create the
reaction pellets. Because of the reducing atmosphere in the setup, a magnetite
layer is formed on the outside of the pellet, which in turn reacts with the Zn
vapor. After reaction, Zn concentration profiles were measured in the reacted
magnetite layer using field-emission gun electron probe microanalysis. The
reaction was confirmed to be diffusion-controlled. The effect of both volume and
grain-boundary diffusion was observed in each experiment. The temperature
dependence of both the volume and grain-boundary diffusion coefficients was
obtained along with the activation energies of the diffusion coefficients. This
study provides crucial information for the development of technologies that are
dependent on the reaction. One example is the in-process separation technology
for the separation of Zn vapor from electric arc furnace off-gas.
PMID- 25844641
TI - Measuring melittin uptake into hydrogel nanoparticles with near-infrared single
nanoparticle surface plasmon resonance microscopy.
AB - This paper describes how changes in the refractive index of single hydrogel
nanoparticles (HNPs) detected with near-infrared surface plasmon resonance
microscopy (SPRM) can be used to monitor the uptake of therapeutic compounds for
potential drug delivery applications. As a first example, SPRM is used to measure
the specific uptake of the bioactive peptide melittin into N-isopropylacrylamide
(NIPAm)-based HNPs. Point diffraction patterns in sequential real-time SPRM
differential reflectivity images are counted to create digital adsorption binding
curves of single 220 nm HNPs from picomolar nanoparticle solutions onto
hydrophobic alkanethiol-modified gold surfaces. For each digital adsorption
binding curve, the average single nanoparticle SPRM reflectivity response,
?Delta%RNP?, was measured. The value of ?Delta%RNP? increased linearly from 1.04
+/- 0.04 to 2.10 +/- 0.10% when the melittin concentration in the HNP solution
varied from zero to 2.5 MUM. No change in the average HNP size in the presence of
melittin is observed with dynamic light scattering measurements, and no increase
in ?Delta%RNP? is observed in the presence of either FLAG octapeptide or bovine
serum albumin. Additional bulk fluorescence measurements of melittin uptake into
HNPs are used to estimate that a 1% increase in ?Delta%RNP? observed in SPRM
corresponds to the incorporation of approximately 65000 molecules into each 220
nm HNP, corresponding to roughly 4% of its volume. The lowest detected amount of
melittin loading into the 220 nm HNPs was an increase in ?Delta%RNP? of 0.15%,
corresponding to the absorption of 10000 molecules.
PMID- 25844642
TI - Relative age effects in athletic sprinting and corrective adjustments as a
solution for their removal.
AB - Relative Age Effects (RAEs) refer to the selection and performance differentials
between children and youth who are categorized in annual-age groups. In the
context of Swiss 60m athletic sprinting, 7761 male athletes aged 8 - 15 years
were analysed, with this study examining whether: (i) RAE prevalence changed
across annual age groups and according to performance level (i.e., all athletes,
Top 50%, 25% & 10%); (ii) whether the relationship between relative age and
performance could be quantified, and corrective adjustments applied to test if
RAEs could be removed. Part one identified that when all athletes were included,
typical RAEs were evident, with smaller comparative effect sizes, and
progressively reduced with older age groups. However, RAE effect sizes increased
linearly according to performance level (i.e., all athletes - Top 10%) regardless
of age group. In part two, all athletes born in each quartile, and within each
annual age group, were entered into linear regression analyses. Results
identified that an almost one year relative age difference resulted in mean
expected performance differences of 10.1% at age 8, 8.4% at 9, 6.8% at 10, 6.4%
at 11, 6.0% at 12, 6.3% at 13, 6.7% at 14, and 5.3% at 15. Correction adjustments
were then calculated according to day, month, quarter, and year, and used to
demonstrate that RAEs can be effectively removed from all performance levels, and
from Swiss junior sprinting more broadly. Such procedures could hold significant
implications for sport participation as well as for performance assessment,
evaluation, and selection during athlete development.
PMID- 25844643
TI - Lipid Selectivity, Orientation, and Extent of Membrane Binding of Nonacylated
RP2.
AB - Retinitis pigmentosa 2 (RP2) is an ubiquitary protein of 350 residues. The N
terminus of RP2 contains putative sites of myristoylation and palmitoylation. The
dually acylated protein is predominantly localized to the plasma membrane.
However, clinically occurring substitution mutations of RP2 in photoreceptors
lead to the expression of a nonacylated protein, which was shown to be misrouted
to intracellular organelles using different cell lines. However, the parameters
responsible for the modulation of the membrane binding of nonacylated RP2 (naRP2)
are still largely unknown. The maximal insertion pressure of naRP2 has thus been
determined after its injection into the subphase underneath monolayers of
phospholipids, which are typical of photoreceptor membranes. These data
demonstrated that naRP2 shows a preferential binding to saturated phospholipid
monolayers. Moreover, polarization modulation infrared reflection absorption
spectroscopy has allowed comparison of the secondary structure of this protein in
solution and upon binding to phospholipid monolayers. In addition, simulations of
these spectra have allowed to determine that the beta-helix of naRP2 has an
orientation of 60 degrees with respect to the normal, which remains unchanged
regardless of the type of phospholipid. Finally, ellipsometric measurements of
naRP2 demonstrated that its particular affinity for saturated phospholipids can
be explained by its larger extent of insertion in this phospholipid monolayer
compared to that in polyunsaturated phospholipid monolayers.
PMID- 25844645
TI - Octanol-Water Partition Coefficient from 3D-RISM-KH Molecular Theory of Solvation
with Partial Molar Volume Correction.
AB - The octanol-water partition coefficient is an important physical-chemical
characteristic widely used to describe hydrophobic/hydrophilic properties of
chemical compounds. The partition coefficient is related to the transfer free
energy of a compound from water to octanol. Here, we introduce a new protocol for
prediction of the partition coefficient based on the statistical-mechanical, 3D
RISM-KH molecular theory of solvation. It was shown recently that with the
compound-solvent correlation functions obtained from the 3D-RISM-KH molecular
theory of solvation, the free energy functional supplemented with the correction
linearly related to the partial molar volume obtained from the Kirkwood-Buff/3D
RISM theory, also called the "universal correction" (UC), provides accurate
prediction of the hydration free energy of small compounds, compared to explicit
solvent molecular dynamics [ Palmer , D. S. ; J. Phys.: Condens. Matter 2010 , 22
, 492101 ]. Here we report that with the UC reparametrized accordingly this
theory also provides an excellent agreement with the experimental data for the
solvation free energy in nonpolar solvent (1-octanol) and so accurately predicts
the octanol-water partition coefficient. The performance of the Kovalenko-Hirata
(KH) and Gaussian fluctuation (GF) functionals of the solvation free energy, with
and without UC, is tested on a large library of small compounds with diverse
functional groups. The best agreement with the experimental data for octanol
water partition coefficients is obtained with the KH-UC solvation free energy
functional.
PMID- 25844644
TI - Restoring susceptibility induced MRI signal loss in rat brain at 9.4 T: A step
towards whole brain functional connectivity imaging.
AB - The aural cavity magnetic susceptibility artifact leads to significant echo
planar imaging (EPI) signal dropout in rat deep brain that limits acquisition of
functional connectivity fcMRI data. In this study, we provide a method that
recovers much of the EPI signal in deep brain. Needle puncture introduction of a
liquid-phase fluorocarbon into the middle ear allows acquisition of rat fcMRI
data without signal dropout. We demonstrate that with seeds chosen from
previously unavailable areas, including the amygdala and the insular cortex, we
are able to acquire large scale networks, including the limbic system. This tool
allows EPI-based neuroscience and pharmaceutical research in rat brain using
fcMRI that was previously not feasible.
PMID- 25844647
TI - High-efficiency thermoelectrics with functionalized graphene.
AB - Graphene superlattices made with chemical functionalization offer the possibility
of tuning both the thermal and electronic properties via nanopatterning of the
graphene surface. Using classical and quantum mechanical calculations, we predict
that suitable chemical functionalization of graphene can introduce peaks in the
density of states at the band edge that result in a large enhancement in the
Seebeck coefficient, leading to an increase in the room-temperature power factor
of a factor of 2 compared to pristine graphene, despite the degraded electrical
conductivity. Furthermore, the presence of patterns on graphene reduces the
thermal conductivity, which when taken together leads to an increase in the
figure of merit for functionalized graphene by up to 2 orders of magnitude over
that of pristine graphene, reaching its maximum ZT ~ 3 at room temperature
according to our calculations. These results suggest that appropriate chemical
functionalization could lead to efficient graphene-based thermoelectric
materials.
PMID- 25844646
TI - Inhibitors of eicosanoid biosynthesis influencing the transcripts level of
sHSP21.4 gene induced by pathogen infections, in Antheraea pernyi.
AB - Small heat shock proteins (sHSPs) can regulate protein folding and protect cells
from stress. To investigate the role of sHSPs in the silk-producing insect
Antheraea pernyi response to microorganisms, a sHsp gene termed as Ap-sHSP21.4,
was identified. This gene encoded a 21.4 kDa protein which shares the conserved
structure of insect sHsps and belongs to sHSP21.4 family. Ap-sHSP21.4 was highly
expressed in fat body and up-regulated in midgut and fat body of A. pernyi
challenged with Escherichia coli, Beauveria bassiana and nuclear polyhedrosis
virus (NPV), which was determined by quantitative real-time PCR. Meanwhile, knock
down of Ap-sHSP21.4 with dsRNA result in the decrease at the expression levels of
several immune response-related genes (defensin, Dopa decarboxylase, Toll1,
lysozyme and Kazal-type serine protease inhibitor). Additionally, the impact of
eicosanoid biosynthesis on the expression of Ap-sHSP21.4 response to NPV was
determined using qPCR, inhibitors of eicosanoid biosynthesis significantly
suppress Ap-HSP21.4 expression upon NPV challenge. All together, Ap-sHSP21.4 was
involved in the immunity of A. pernyi against microorganism and possibly mediated
by eicosanoids pathway. These results will shed light in the understanding of the
pathogen-host interaction in A. pernyi.
PMID- 25844648
TI - Removal of natural estrogens and their conjugates in municipal wastewater
treatment plants: a critical review.
AB - This article reviews studies focusing on the removal performance of natural
estrogens in municipal wastewater treatment plants (WWTPs). Key factors
influencing removal include: sludge retention time (SRT), aeration, temperature,
mixed liquor suspended solids (MLSS), and substrate concentration. Batch studies
show that natural estrogens should biodegrade well; however, batch observations
do not always agree with observations from full-scale municipal WWTPs. To explain
this discrepancy, deconjugation kinetics of estrogen conjugates in lab-scale
studies were examined and compared. Most estrogen conjugates with slow
deconjugation rates are unlikely to be easily removed; others could be cleaved in
WWTP settings. Nevertheless, some estrogens cleaved from their conjugates may be
found in treated effluent, because deconjugation requires several hours or
longer, and there is insufficient rest time for the biodegradation of the cleaved
natural estrogens in the WWTP. Therefore, WWTP removals of natural estrogens are
likely to be underestimated when estrogen conjugates are present in raw
wastewater. This review suggests that biodeconjugation of estrogen conjugates
should be enhanced to more effectively remove natural estrogens in WWTPs.
PMID- 25844649
TI - National accounts of subjective well-being.
AB - Diener (2000) proposed that National Accounts of Well-Being be created to
complement existing economic and social indicators that reflect the quality of
life in nations. These national accounts can provide valuable information to
policymakers and other leaders. Systematic measurement of subjective well-being
provides novel information about the quality of life in societies, and it allows
for the accumulation of detailed information regarding the circumstances that are
associated with high subjective well-being. Thus, accounts of subjective well
being can help decision makers evaluate policies that improve societies beyond
economic development. Progress with well-being accounts has been notable:
Prestigious scientific and international institutions have recommended the
creation of such national accounts, and these recommendations have been adopted
in some form in over 40 nations. In addition, increasing research into policy
relevant questions reveals the importance of the accounts for policy.
Psychologists can enlarge their role in the formulation and adoption of policies
by actively studying and using accounts of subjective well-being to evaluate and
support the policies they believe are needed.
PMID- 25844650
TI - Strengthening psychology's workforce for older adults: Implications of the
Institute of Medicine's report to Congress.
AB - Professional psychology faces an urgent crisis, which the following facts paint
in stark relief. Adults over age 65 will rise to 20% of the U.S. population over
the next 15 years and already account for a third of the country's health care
expenditures. Up to 8 million older adults experience mental health and substance
use conditions in a given year, yet most psychologists receive no training in
their assessment and treatment. No more than an estimated 4%, or 3,000,
psychologists nationwide specialize in geropsychology; a ratio approaching 3,000
to 1. A small group of advocates within the profession have sounded the alarm and
worked to strengthen geropsychology as a specialty, but this has had very limited
impact on the actual supply of psychologists qualified to provide services to
this population. In 2012, an Institute of Medicine (IOM) committee released a
report on the crisis regarding the mental health and substance use workforce for
older adults. Drawing on that report, a team composed of geropsychologists, along
with psychologists who served on the IOM committee, identifies in this article
priority areas for workforce development. The authors assess the progress of
psychology in each of these areas and offer a set of recommendations for future
efforts by this profession to develop its own workforce and to strengthen the
ability of other caregivers to address the behavioral health needs of older
adults. Strengthening its own workforce and responding to the needs of this
population is imperative if psychology is to maintain its relevance as a health
profession and meet its ethical obligations to an increasingly diverse society.
PMID- 25844651
TI - Phyllis Bronstein (1939-2012).
AB - This article memorializes Phyllis Bronstein (1939-2012). Bronstein was a feminist
scholar, social and clinical psychologist, and activist for social justice. At
the University of Vermont, she engaged almost 100 undergraduates in her research
teams, mentored the research and professional development of 43 graduate
students, and trained over 90 clinical psychology students in the feminist family
therapy program she developed. Bronstein published over 45 chapters and journal
articles, and three edited books. One stream of her scholarship focused on
sociocultural factors in parenting, child and adolescent development, with
studies conducted in the United States and Mexico. Bronstein is perhaps best
known for two volumes on the integration of multicultural and gender issues into
the psychology curriculum, coedited with Kathryn Quina and published by the
American Psychological Association. Bronstein's third stream of scholarship
addressed sexist, racist, and ageist practices in academic and clinical
professions.
PMID- 25844652
TI - Sandra Lipsitz Bem (1944-2014).
AB - This article memorializes Sandra Lipsitz Bem (1944-2014). Bem was a feminism
psychologist whose incisive writing and research transformed the psychology of
gender and contributed significantly to our understanding of sex-typing,
psychological androgyny, gender schema theory, and sexual inequality. Bem and her
husband, Daryl Bem, were active in the feminist community in Pittsburgh, and
worked with the National Organization for Women to challenge gender-segregated
job advertisements in a lawsuit against the Pittsburgh Press in 1969. The Bems co
wrote an influential article, "Case Study of a Nonconscious Ideology: Training
the Woman to Know Her Place" (1970) using the word "sexism" when it was not
widely known. She created the Bem Sex-Role Inventory (BSRI) and conducted
research showing that conventional gender typing was not necessarily correlated
with psychological adjustment. Her publications won her enduring recognition and
awards, including the American Psychological Association Distinguished Scientific
Award for Early Career Contribution (1976), Distinguished Publication Awards from
the Association for Women in Psychology (AWP; 1977, 1994), the Young Scholar
Award from the American Association of University Women (1980), and,
posthumously, the Distinguished Career Award (AWP, 2014).
PMID- 25844653
TI - Selma Sapir (1916-2014).
AB - This article memorializes Selma Sapir (1916-2014), a child psychologist and
innovator in treating children with learning disabilities. Sapir authored or
coauthored five books on treating and educating children with learning
disabilities. She developed four tests: the Sapir Dimension of Learning, the
Sapir Learning Lab Language Scale, the Sapir Self-Concept Scale, and the Sapir
Developmental Scale. In 1997-1998, she served as president of the International
Council of Psychologists (ICP). For many years, she was the ICP representative to
the United Nations.
PMID- 25844654
TI - Robert E. Thayer (1935-2014).
AB - This article memorializes Robert E. Thayer (1935-2014). He was an internationally
recognized leader in research into human mood, with influence inside and outside
of the academy. In articles and books he advanced our understanding of the bases
of human moods and the role mood plays in everyday life. His seminal work
examined the biopsychology of mood, including a range of factors such as energy,
tension, and arousal. He also developed a mood-related measure, the Activation
Deactivation Adjective Check List (1964).
PMID- 25844655
TI - Comment on the January 2015 cover of the American Psychologist.
AB - This article comments on the January 2015 cover of the American Psychologist
(Vol. 70, Issue 1). The caption linked to a picture of a wintry mountain scene
said "Squaw Valley Meadow." Although a seemingly innocuous word to most people, a
majority of Society of Indian Psychologists (SIP) members wanted to share what
the term squaw , hereinafter deemed "s-word," invokes for many Native individuals
as well as in the collective cultural memories of American Indian peoples. As a
voice representative of Native peoples, the members of SIP are acutely aware of
the many issues that need to be redressed, both within our own communities and in
our relations with non-Native society. In the case of the cover art caption and
the ire provoked by the use of the s-word, the members of SIP opted to take an
opportunity to educate versus confront, and to inform versus chastise or accuse
amid this polarized political climate of interracial tensions.
PMID- 25844656
TI - Chronic pain and the adaptive significance of positive emotions.
AB - The February-March 2014 special issue of the American Psychologist featured
articles summarizing select contributions from the field of psychology to the
assessment and treatment of chronic pain. The articles examined a range of
psychosocial and family factors that influence individual adjustment and
contribute to disparities in pain care. The reviews also considered the
psychological correlates and neurophysiological mechanisms of specific pain
treatments, including cognitive-behavioral therapy, hypnosis, acceptance and
commitment therapy, mindfulness, and meditation. Although a number of articles
emphasized the role that negative states of mind play in pain outcomes, positive
emotions were given only brief mention. Here, we provide a rationale for the
inclusion of positive emotions in chronic pain research.
PMID- 25844657
TI - Tarasoff's catch-22.
AB - Comments on the article by D. N. Bersoff (see record 2014-28692-002). Bersoff
poses a much-needed challenge to the rationale of laws based on Tarasoff v.
Regents of the University of California (1976), which exist in most states and
require therapists to warn the intended victim, police, and/or others when a
patient voices serious threats of violence. If Tarasoff-related laws were ever to
be modified, research support would be required. To begin with, what is the
experience of other countries that happen to address this issue differently and
of the seven states that, according to Bersoff, have not adopted Tarasoff-related
requirements? Another question is whether patients who are unwilling to invite
the consequences of therapist disclosure ever reveal reportable intentions to
their therapists anyway-say, by mistake or impulse-thus making current law
marginally useful? Rules that undercut sacrosanct confidentiality create a catch
22 in which the indisputable ethical necessity of informed consent has an
unintended consequence- namely, therapy is preceded by informed consent but
precluded by it.
PMID- 25844658
TI - Plasmonic fano nanoantennas for on-chip separation of wavelength-encoded optical
signals.
AB - Here we suggest and realize an ultracompact plasmonic spectral-band demultiplexer
for telecommunication wavelengths integrated onto an optical waveguide that
couples two wavelength-encoded optical signals in the O- and the C-band in
opposite directions of a silicon waveguide. In this way, we demonstrate a
plasmonic key element for on-chip optical data processing that can also be used
as a functional link between on- and off-chip optical signals.
PMID- 25844659
TI - Reactivity of CuI and CuBr toward dialkyl sulfides RSR: from discrete molecular
Cu4I4S4 and Cu8I8S6 clusters to luminescent copper(I) coordination polymers.
AB - The 1D coordination polymer (CP) [(Me2S)3{Cu2(MU-I)2}]n (1) is formed when CuI
reacts with SMe2 in n-heptane, whereas in acetonitrile (MeCN), the reaction forms
exclusively the 2D CP [(Me2S)3{Cu4(MU-I)4}]n (2) containing "flower-basket" Cu4I4
units. The reaction product of CuI with MeSEt is also solvent-dependent, where
the 1D polymer [(MeSEt)2{Cu4(MU3-I)2(MU2-I)2}(MeCN)2]n (3) containing "stepped
cubane" Cu4I4 units is isolated in MeCN. In contrast, the reaction in n-heptane
affords the 1D CP [(MeSEt)3{Cu4(MU3-I)4}]n (4) containing "closed-cubane" Cu4I4
clusters. The reaction of MeSPr with CuI provides the structurally related 1D CP
[(MeSPr)3{Cu4(MU3-I)4}]n (5), for which the X-ray structure has been determined
at 115, 155, 195, 235, and 275 K, addressing the evolution of the metric
parameters. Similarly to 4 and the previously reported CP [(Et2S)3{Cu4(MU3-I)4}]n
(Inorg. Chem. 2010, 49, 5834), the 1D chain is built upon closed cubanes Cu4(MU3
I)4 as secondary building units (SBUs) interconnected via MU-MeSPr ligands. The
0D tetranuclear clusters [(L)4{Cu4(MU3-I)4}] [L = EtSPr (6), Pr2S (7)]
respectively result from the reaction of CuI with EtSPr and n-Pr2S. With i-Pr2S,
the octanuclear cluster [(i-Pr2S)6{Cu8(MU3-I)3}(MU4-I)2}] (8) is formed. An X-ray
study has also been performed at five different temperatures for the 2D polymer
[(Cu3Br3)(MeSEt)3]n (9) formed from the reaction between CuBr and MeSEt in
heptane. The unprecedented framework of 9 consists of layers with alternating
Cu(MU2-Br)2Cu rhomboids, which are connected through two MU-MeSEt ligands to
tetranuclear open-cubane Cu4Br4 SBUs. MeSPr forms with CuBr in heptane the 1D CP
[(Cu3Br3)(MeSPr)3]n (10), which is converted to a 2D metal-organic framework
[(Cu5Br5)(MU2-MeSPr)3]n (11) incorporating pentanuclear [(Cu5(MU4-Br)(MU2-Br)]
SBUs when recrystallized in MeCN. The thermal stability and photophysical
properties of these materials are also reported.
PMID- 25844660
TI - Implementation and impact of an extended-hours service in mental health care:
lessons learned.
AB - OBJECTIVE: To describe the activity and impact of an extended-hours mental health
service established to meet perceived need and improve service efficiency.
Lessons developed in evaluation could usefully inform development of services in
similar settings. SETTING: A specialist mental health service providing
assessment and treatment to 330 000 catchment residents of an Australian capital
city. METHODS: Pragmatic mixed-methods evaluation, combining review of 12 months
service data and interviews with 65 stakeholders; with integration of descriptive
statistics and thematic analysis of qualitative data. RESULTS: Over 12 months,
2040 individuals were provided with a range of services during extended-hours,
indicating that some sort of service was needed. However, evaluation demonstrated
that flaws in assumptions underpinning the extended-hours service design,
particularly regarding the population seeking after-hours care, necessitated
adaptation of the proposed model. Ambiguity in purpose contributed to perceived
lack of a cohesive identity, compounded by critical differences in the
philosophies of care teams from which the extended-hours service clinicians were
drawn. Nonetheless the service was considered effective by many stakeholders and
co-location of different teams built collegiality within the service.
CONCLUSIONS: A comprehensive needs analysis, enabling full description of target
populations and their needs, should underpin establishment of any service. Such
understanding is needed to ensure resources are appropriate. Importantly, because
mental health clinicians are not interchangeable, matching philosophy of care and
clinical skills to identified need is critical to quality and efficiency.
PMID- 25844661
TI - Substrate activation strategies in rhodium(III)-catalyzed selective
functionalization of arenes.
AB - The possibility of developing new methods for the efficient construction of
organic molecules via disconnections other than traditional functional group
transformations has driven the interest in direct functionalization of C-H bonds.
The ubiquity of C-H bonds makes such transformations attractive, but they also
pose several challenges. The first is the reactivity and selectivity of C-H
bonds. To achieve this, directing groups (DGs) are often installed that can
enhance the effective concentration of the catalyst, leading to thermodynamically
stable metallacyclic intermediates. However, the presence of a pendant directing
group in the product is often undesirable and unnecessary. This may account for
the limitation of applications of C-H functionalization reactions in more common
and general uses. Thus, the development of removable or functionalizable
directing groups is desirable. Another key problem is that the reactivity of the
resulting M-C bond can be low, which may limit the scope of the coupling partners
and hence limit the reaction patterns of C-H activation reactions. While the
first Cp*Rh(III)-catalyzed C-H activation of arenes was reported only 7 years
ago, significant progress has been made in this area in the past few years. We
began our studies in this area in 2010, and we and others have demonstrated that
diversified catalytic functionalization of arenes can be realized using
Cp*Rh(III) complexes with high reactivity, stability, and functional group
compatibility. This Account describes our efforts to solve some of these
challenges using Rh(III) catalysis. We fulfilled our design and activation of the
arene substrates by taking advantage of the nucleophilicity, electrophilicity,
oxidizing potential, and properties of a participating ligand of the directing
groups when the arenes are coupled with relatively reactive unsaturated partners
such as alkenes and alkynes. These in situ funtionalizable roles of the DG
allowed extensive chemical manipulation of the initial coupled product,
especially in the construction of a diverse array of heterocycles. In the
coupling of arenes with polar coupling partners, the polar Rh(III)-C(aryl) bond
showed higher reactivity as both an organometallic reagent and a nucleophilic
aryl source. The polar coupling partners were accordingly activated by virtue of
umpolung, ring strain, and rearomatization. All of these transformations have
been made possible by integration of the higher reactivity, stability, and
compatibility of Rh(III)-C bonds into catalytic systems. We have demonstrated
that to date some of these transformations can be achieved only under rhodium
catalysis. In addition, by means of stoichiometric reactions, we have gained
mechanistic insights into the interactions between the Rh-C bond and the other
coupling partners, which have opened new avenues in future direct C-H
functionalization reactions.
PMID- 25844662
TI - Estimation of polycyclic aromatic hydrocarbon variability in air using high
volume, film, and vegetation as samplers.
AB - Organic films and leaves provide a medium into which organic contaminants, such
as polycyclic aromatic hydrocarbons (PAHs), can accumulate, resulting in a useful
passive air sampler. In the present work, the temporal variability (weekly) in
PAH concentrations and the fingerprint of films developed on window surfaces were
investigated. Moreover, films and leaves of two tree species (Acer pseudoplatanus
and Cornus mas) collected at the same time were used to derive PAH air
concentrations and investigate their short-term variability. In general, the most
abundant chemicals found in films were phenanthrene and pyrene (22%), followed by
perylene (21%) and fluoranthene (16%), but the fingerprint (in contrast to leaves
and air) changed over time. Leaf derived air concentrations were within a factor
of 2 to 9 from measured values, while air concentrations back-calculated from
films were within a factor of 2 to 53. This happened because predicted air
concentrations using films and vegetation samplers (especially for low KOA
chemicals) generally reflect only the last few hours (due to the fast
equilibrium) of the weekly integrated samples obtained employing the high-volume
sampler. This means that films and leaves can be usefully employed for predicting
the short-term variability of low KOA organic contaminant air concentrations.
PMID- 25844663
TI - Spatial Accessibility to HIV Providers in Atlanta, Georgia.
PMID- 25844664
TI - Shape-Dependent Multiexciton Emission and Whispering Gallery Modes in
Supraparticles of CdSe/Multishell Quantum Dots.
AB - Semiconductors are indispensable as the active light-emitting element in many
optoelectronic devices. However, even the purest bulk semiconductors suffer from
considerable nonradiative recombination leading to low photoluminescence
efficiencies. Zero-dimensional quantum dots show a much better carrier-to-photon
conversion caused by confinement of the excitons but suffer from nonradiative
recombination when assembled into a solid, due to exciton energy transfer. Here,
we report on the shape-dependent optical properties of self-assembled
supraparticles composed of CdSe/multishell nanocrystals. All supraparticles show
stable and bright photoluminescence in ambient up to high excitation intensities.
When the supraparticles are deposited on a silicon surface their spherical shape
is deformed due to drying. In addition to single-exciton emission, we observe
bright emission from multiexciton states at high excitation powers. In contrast,
supraparticles that retain their perfectly spherical shape show a spectrum with
sharp Mie whispering gallery modes, while multiexciton emission is absent.
PMID- 25844665
TI - Preface: RECOMB/ISCB systems biology, regulatory genomics, and DREAM 2014 Special
Issue.
PMID- 25844666
TI - Multi-species network inference improves gene regulatory network reconstruction
for early embryonic development in Drosophila.
AB - Gene regulatory network inference uses genome-wide transcriptome measurements in
response to genetic, environmental, or dynamic perturbations to predict causal
regulatory influences between genes. We hypothesized that evolution also acts as
a suitable network perturbation and that integration of data from multiple
closely related species can lead to improved reconstruction of gene regulatory
networks. To test this hypothesis, we predicted networks from temporal gene
expression data for 3,610 genes measured during early embryonic development in
six Drosophila species and compared predicted networks to gold standard networks
of ChIP-chip and ChIP-seq interactions for developmental transcription factors in
five species. We found that (i) the performance of single-species networks was
independent of the species where the gold standard was measured; (ii) differences
between predicted networks reflected the known phylogeny and differences in
biology between the species; (iii) an integrative consensus network that
minimized the total number of edge gains and losses with respect to all single
species networks performed better than any individual network. Our results show
that in an evolutionarily conserved system, integration of data from comparable
experiments in multiple species improves the inference of gene regulatory
networks. They provide a basis for future studies on the numerous multispecies
gene expression datasets for other biological processes available in the
literature.
PMID- 25844668
TI - A canonical correlation analysis-based dynamic bayesian network prior to infer
gene regulatory networks from multiple types of biological data.
AB - One of the challenging and important computational problems in systems biology is
to infer gene regulatory networks (GRNs) of biological systems. Several methods
that exploit gene expression data have been developed to tackle this problem. In
this study, we propose the use of copy number and DNA methylation data to infer
GRNs. We developed an algorithm that scores regulatory interactions between genes
based on canonical correlation analysis. In this algorithm, copy number or DNA
methylation variables are treated as potential regulator variables, and
expression variables are treated as potential target variables. We first
validated that the canonical correlation analysis method is able to infer true
interactions in high accuracy. We showed that the use of DNA methylation or copy
number datasets leads to improved inference over steady-state expression. Our
results also showed that epigenetic and structural information could be used to
infer directionality of regulatory interactions. Additional improvements in GRN
inference can be gleaned from incorporating the result in an informative prior in
a dynamic Bayesian algorithm. This is the first study that incorporates copy
number and DNA methylation into an informative prior in dynamic Bayesian
framework. By closely examining top-scoring interactions with different sources
of epigenetic or structural information, we also identified potential novel
regulatory interactions.
PMID- 25844667
TI - A scalable method for molecular network reconstruction identifies properties of
targets and mutations in acute myeloid leukemia.
AB - A key aim of systems biology is the reconstruction of molecular networks. We do
not yet, however, have networks that integrate information from all datasets
available for a particular clinical condition. This is in part due to the limited
scalability, in terms of required computational time and power, of existing
algorithms. Network reconstruction methods should also be scalable in the sense
of allowing scientists from different backgrounds to efficiently integrate
additional data. We present a network model of acute myeloid leukemia (AML). In
the current version (AML 2.1), we have used gene expression data (both microarray
and RNA-seq) from 5 different studies comprising a total of 771 AML samples and a
protein-protein interactions dataset. Our scalable network reconstruction method
is in part based on the well-known property of gene expression correlation among
interacting molecules. The difficulty of distinguishing between direct and
indirect interactions is addressed by optimizing the coefficient of variation of
gene expression, using a validated gold-standard dataset of direct interactions.
Computational time is much reduced compared to other network reconstruction
methods. A key feature is the study of the reproducibility of interactions found
in independent clinical datasets. An analysis of the most significant clusters,
and of the network properties (intraset efficiency, degree, betweenness
centrality, and PageRank) of common AML mutations demonstrated the biological
significance of the network. A statistical analysis of the response of blast
cells from 11 AML patients to a library of kinase inhibitors provided an
experimental validation of the network. A combination of network and experimental
data identified CDK1, CDK2, CDK4, and CDK6 and other kinases as potential
therapeutic targets in AML.
PMID- 25844669
TI - Inferring genome-wide functional modulatory network: a case study on NF
kappaB/RelA transcription factor.
AB - How different pathways lead to the activation of a specific transcription factor
(TF) with specific effects is not fully understood. We model context-specific
transcriptional regulation as a modulatory network: triplets composed of a TF,
target gene, and modulator. Modulators usually affect the activity of a specific
TF at the posttranscriptional level in a target gene-specific action mode. This
action may be classified as enhancement, attenuation, or inversion of either
activation or inhibition. As a case study, we inferred, from a large collection
of expression profiles, all potential modulations of NF-kappaB/RelA. The
predicted modulators include many proteins previously not reported as physically
binding to RelA but with relevant functions, such as RNA processing, cell cycle,
mitochondrion, ubiquitin-dependent proteolysis, and chromatin modification.
Modulators from different processes exert specific prevalent action modes on
distinct pathways. Modulators from noncoding RNA, RNA-binding proteins, TFs, and
kinases modulate the NF-kappaB/RelA activity with specific action modes
consistent with their molecular functions and modulation level. The modulatory
networks of NF-kappaB/RelA in the context epithelial-mesenchymal transition (EMT)
and burn injury have different modulators, including those involved in
extracellular matrix (FBN1), cytoskeletal regulation (ACTN1), and metastasis
associated lung adenocarcinoma transcript 1 (MALAT1), a long intergenic
nonprotein coding RNA, and tumor suppression (FOXP1) for EMT, and TXNIP, GAPDH,
PKM2, IFIT5, LDHA, NID1, and TPP1 for burn injury.
PMID- 25844670
TI - Disease gene prioritization using network and feature.
AB - Identifying high-confidence candidate genes that are causative for disease
phenotypes, from the large lists of variations produced by high-throughput
genomics, can be both time-consuming and costly. The development of novel
computational approaches, utilizing existing biological knowledge for the
prioritization of such candidate genes, can improve the efficiency and accuracy
of the biomedical data analysis. It can also reduce the cost of such studies by
avoiding experimental validations of irrelevant candidates. In this study, we
address this challenge by proposing a novel gene prioritization approach that
ranks promising candidate genes that are likely to be involved in a disease or
phenotype under study. This algorithm is based on the modified conditional random
field (CRF) model that simultaneously makes use of both gene annotations and gene
interactions, while preserving their original representation. We validated our
approach on two independent disease benchmark studies by ranking candidate genes
using network and feature information. Our results showed both high area under
the curve (AUC) value (0.86), and more importantly high partial AUC (pAUC) value
(0.1296), and revealed higher accuracy and precision at the top predictions as
compared with other well-performed gene prioritization tools, such as Endeavour
(AUC-0.82, pAUC-0.083) and PINTA (AUC-0.76, pAUC-0.066). We were able to detect
more target genes (9/18/19/27) on top positions (1/5/10/20) compared to Endeavour
(3/11/14/23) and PINTA (6/10/13/18). To demonstrate its usability, we applied our
method to a case study for the prediction of molecular mechanisms contributing to
intellectual disability and autism. Our approach was able to correctly recover
genes related to both disorders and provide suggestions for possible additional
candidates based on their rankings and functional annotations.
PMID- 25844671
TI - cDREM: inferring dynamic combinatorial gene regulation.
AB - Genes are often combinatorially regulated by multiple transcription factors
(TFs). Such combinatorial regulation plays an important role in development and
facilitates the ability of cells to respond to different stresses. While a number
of approaches have utilized sequence and ChIP-based datasets to study
combinational regulation, these have often ignored the combinational logic and
the dynamics associated with such regulation. Here we present cDREM, a new method
for reconstructing dynamic models of combinatorial regulation. cDREM integrates
time series gene expression data with (static) protein interaction data. The
method is based on a hidden Markov model and utilizes the sparse group Lasso to
identify small subsets of combinatorially active TFs, their time of activation,
and the logical function they implement. We tested cDREM on yeast and human data
sets. Using yeast we show that the predicted combinatorial sets agree with other
high throughput genomic datasets and improve upon prior methods developed to
infer combinatorial regulation. Applying cDREM to study human response to flu, we
were able to identify several combinatorial TF sets, some of which were known to
regulate immune response while others represent novel combinations of important
TFs.
PMID- 25844672
TI - The Cry of the Child and its Relationship to Hearing Loss in Parental Guardians
and Health Care Providers.
AB - In this study the authors investigate the sound pressure levels produced by
crying children and discuss the possible adverse effects that direct exposure may
impose on a tending guardian or healthcare professional. Sound intensity levels
from various pediatric patients (N = 26) were measured under two segregate
conditions, one imitating the exposure of an examining physician and the other
resembling that of parental guardians. Interestingly, all of the recorded sound
levels fell between 99-120 dB(A) of sound pressure; children presenting the
greatest risk for intense cries with potentially harmful sound intensities were
between the ages of 9 months and 6 years. The authors found that elevated noise
levels produced from crying children can cause acute discomfort and mild pain to
those exposed. In addition, there is a theoretical risk that chronic exposure to
these intense sound pressures may result in noise-induced hearing loss in a
parental guardian or an examining physician. Parents of young children may be
more likely to succumb to impulsive reactions in attempting to arrest the crying,
which could be a precipitating factor for child abuse, responding to physical
stress as much as emotional stress. Social workers and medical personnel should
consider suggesting the use of ear plugs by parental guardians of frequently
crying children as a modality for the prevention of child abuse.
PMID- 25844673
TI - A mixed phenotype of airway wall thickening and emphysema is associated with
dyspnea and hospitalization for chronic obstructive pulmonary disease.
AB - RATIONALE: Quantitative computed tomography (CT) has been used to phenotype
patients with chronic obstructive pulmonary disease (COPD). A mixed phenotype is
defined as the presence of both airway wall thickening and emphysema on
quantitative CT. Little is known about patients with COPD with the mixed
phenotype. OBJECTIVES: To propose a method of phenotyping COPD based on
quantitative CT and to compare clinically relevant outcomes between patients with
COPD with the mixed phenotype and those with other CT-based phenotypes. METHODS:
Each of 427 male smokers (187 without COPD, 240 with COPD) underwent a complete
medical interview, pulmonary function testing, and whole-lung CT on the same day.
The percentage of low-attenuation volume at the threshold of -950 Hounsfield
units (%LAV) and the square root of wall area of a hypothetical airway with an
internal perimeter of 10 mm (Pi10) were measured. Patients with COPD were
classified into four distinct phenotypes based on the upper limits of normal for
%LAV and Pi10, which were derived from the data of smokers without COPD by using
quantile regression. MEASUREMENTS AND MAIN RESULTS: Of 240 patients with COPD, 52
(21.7%) were classified as CT-normal phenotype, 39 (16.3%) as airway-dominant
phenotype, 103 (42.9%) as emphysema-dominant phenotype, and 46 (19.2%) as mixed
phenotype. Patients with COPD with the mixed phenotype were associated with more
severe dyspnea than those with each of the remaining CT-based phenotypes (P <
0.01 for all comparisons). The number of hospitalizations for COPD exacerbations
during the preceding year was 2.0 to 3.6 times higher in patients with the mixed
phenotype than in those with each of the remaining CT-based phenotypes (P < 0.05
for all comparisons). Findings persisted after adjustment for age, pack-years of
smoking, smoking status, body mass index, and FEV1. CONCLUSIONS: Patients with
COPD with the mixed phenotype are associated with more severe dyspnea and more
frequent hospitalizations than those with each of the remaining CT-based
phenotypes. Thus, patients with COPD with the mixed phenotype may need more
attention and interventions.
PMID- 25844674
TI - Metastatic carcinoma of unknown primary: diagnostic approach using
immunohistochemistry.
AB - Carcinoma of unknown primary origin (CUP) is one of the 10 most prevalent
malignancies. CUP patients in whom a site of origin can be ascribed have better
outcomes than those in which the primary tumor remains unidentified. Among the
tools available to pathologists in approaching these lesions,
immunohistochemistry is a reliable, inexpensive, and widely available resource.
New markers continue to emerge, which, in combination with other historically
useful antibodies, allow rapid and accurate identification of primary site in an
increasing number of cases. This review discusses the approach to the diagnosis
of CUP using immunohistochemistry and outlines some of the most useful markers
with a particular focus on the utility of lineage-restricted transcription
factors, including CDX2, NKX3-1, PAX8, SATB2, TTF-1, and SF1.
PMID- 25844675
TI - Aggressive B-cell lymphomas: a review and practical approach for the practicing
pathologist.
AB - Recent advances in diffuse large B-cell lymphoma are changing the way
pathologists approach, diagnose, and report on this heterogeneous group of
lymphomas. The purpose of this review is to provide a practical yet comprehensive
approach to diffuse large B-cell lymphoma and aggressive B-cell lymphomas that
can be used and easily interpreted by pathologists at all levels of training. It
will address important concepts and current testing modalities which provide
important prognostic information for the clinician when considering appropriate
chemotherapeutic regimens for each patient's lymphoma diagnosis. It will also
provide some insights into recently reported signaling pathways and molecular
alterations and their contribution to lymphomagenesis and how identifying these
abnormalities may provide future potential therapeutic targets for these
aggressive lymphomas.
PMID- 25844676
TI - Clear cell proliferations of the skin.
AB - Clear cell proliferations of the skin consist of a diverse group of lesions
characterized by the presence of cells with abundant clear cytoplasm. They may
arise from primary, metastatic, or non-neoplastic origins, with their distinctive
cytoplasmic clearing attributable to causes ranging from artifact to accumulation
of materials such as glycogen, mucin, or lipids. Despite the heterogeneity of
these lesions, their distinguishing characteristics may be subtle, especially at
high power. As such, histologic diagnosis can be challenging, and proper
consideration relies on an understanding of the scope of possible origins,
etiologies, and key immunohistochemical staining patterns of the various
entities. This review categorizes cutaneous clear cell neoplasms by histogenesis,
and offers differential diagnostic strategies to aid in their clinicopathologic
evaluation.
PMID- 25844677
TI - HER2 testing in gastric and gastroesophageal adenocarcinomas.
AB - The human epidermal growth factor receptor 2 (HER2) is overexpressed in 10% to
35% of gastric and gastroesophageal junction (GEJ) adenocarcinomas. In 2010, the
phase III Trastuzumab for Gastric Cancer (ToGA) trial showed that addition of the
anti-HER2 monoclonal antibody trastuzumab to chemotherapy significantly improved
survival of patients with advanced or metastatic tumors that were positive for
HER2 overexpression. As a result, HER2 testing is now recommended for all
patients with advanced or metastatic disease, although there is still some debate
as to the optimal methods of assessment. HER2 expression in gastric and GEJ
tumors shows several differences compared with breast tumors and, for this
reason, the proposed criteria for scoring HER2 expression in biopsies and
resections of gastric and GEJ carcinomas differ from those used in breast
carcinomas. This review discusses what is currently known about the patterns of
HER2 expression in gastric and GEJ adenocarcinomas, summarizes the findings of
the ToGA trial and its clinical implications, and provides an overview of the
recommended guidelines for the most accurate evaluation of HER2 status in gastric
and GEJ cancer.
PMID- 25844678
TI - Intratubular germ cell neoplasia of the testis: a brief review.
AB - Germ cell tumors of the testis may be divided into 3 broad categories according
to age at presentation. The tumors in the pediatric age group include teratoma
and yolk sac tumor. These tumors are generally not associated with convincing
intratubular neoplasia. The second group consists of tumors presenting in third
and fourth decade of life and include seminoma, embryonal carcinoma, yolk sac
tumor, choriocarcinoma, and teratoma as well as mixed germ cell tumors. The
precursor cell for these tumors is an abnormal gonocyte that fails to
differentiate completely into spermatogonia. These abnormal cells stay dormant in
the gonad during intrauterine life as well as infancy and childhood, but undergo
proliferation during puberty and can be identified as intratubular germ cell
neoplasia unclassified (IGCNU). These tumor cells continue to manifest protein
expression pattern that resembles primitive germ cells (PLAP, c-KIT, OCT3/4).
After a variable interval following puberty, IGCNU cells may acquire ability to
penetrate the seminiferous tubules and present as an overt germ cell tumor.
Acquisition of isochrome 12 and other genetic abnormalities are usually
associated with this transition. The level of DNA methylation generally
determines the phenotype of the germ cell tumor. The third type of germ cell
tumors is spermatocytic seminoma, which is a rare tumor encountered later in life
usually in fifth and sixth decade. The cell of origin of this tumor is probably
postpubertal mature spermatogonia which acquire abnormal proliferative capability
probably due to gain of chromosome 9 resulting in activation and amplification of
genes such as DMRT1. The tumor cells manifest many of the proteins normally
expressed by mature sperms such as VASA, SSX2, and occasionally OCT2. Although
spermatocytic seminoma may also have an intratubular growth phase, it completely
lacks features of IGCNU.
PMID- 25844679
TI - A discussion of some advancements and some persistent difficulties in the
recognition and understanding of the histopathologic and molecular features of
selected odontogenic tumors and tumor-like malformations.
AB - Overgrowths of epithelial, ectomesenchymal, and/or mesenchymal elements of the
tooth-forming apparatus are quite variable with respect to their histopathologic
characteristics and biological behaviors. Investigations of a variety of
odontogenic lesions have led to an enhanced comprehension of many salient
diagnostic features. This discussion provides an update with respect to the
understanding of odontogenic tumors and tumor-like malformations and attempts to
assist pathologists in the recognition and classification of these lesions.
PMID- 25844680
TI - Selected case from the Arkadi M. Rywlin International Pathology Slide Club:
carcinoma of the transverse colon in a young girl.
AB - We report a case of a 14-year-old female with primary adenocarcinoma of the
transverse colon. She was hospitalized after presenting with abdominal pain and
signs of intestinal obstruction. There was no health antecedent or family history
of neoplasia. Physical examination revealed a distended abdomen. Tenderness was
elicited to palpation of the right lower quadrant. Magnetic resonance imaging of
the abdomen revealed obstructive signs, with a constricting lesion in the mid
transverse colon of probable neoplastic nature. Laparoscopic segmental resection
of the colon was followed by standard right hemicolectomy. A circumferential mid
transverse tumor was diagnosed as primary colorectal carcinoma (CRC) of signet
ring cell type, AJCC stage IIIC, Dukes' C stage. On the basis of
immunohistochemistry and clinical data, hereditary nonpolyposis and hamartomatous
colorectal cancer syndromes were excluded. Involvement of either the p53, BRAF,
or K-RAS genes was ruled out by immunohistochemistry profiling and genetic
testing. The neoplasm was categorized as sporadic. The possibility of activation
of the Wnt signaling pathway was suspected, because of a defective turnover of
the beta-catenin protein. Postoperatively, the patient was treated with both
systemic and intra-abdominal adjuvant chemotherapy, including oxaliplatin.
Between 18 and 24 months after diagnosis, intra-abdominal tumor recurrences were
detected. The patient underwent bilateral oophorectomies for Krukenberg tumors
and received salvage chemotherapy. Recently, additional recurrent metastatic
retroperitoneal disease caused hydronephrosis. The retroperitoneal mass was
debulked and a ureteric stent was placed. At the time of this writing, 43 months
after diagnosis, the patient is receiving FOLFOX chemotherapy combined with
panitumumab. CRC of childhood is exceedingly rare, generally develops in the
setting of unrecognized genetic predisposing factors to cancer, presents with
advanced disease, is high grade, and tends to have dismal prognosis.
PMID- 25844681
TI - Low-level light/laser therapy versus photobiomodulation therapy.
PMID- 25844682
TI - Clinical evaluation of the Er,Cr:YSGG Laser therapy in the treatment of denture
related traumatic ulcerations: a randomized controlled clinical study.
AB - OBJECTIVE: The aim of this study was to evaluate the efficacy of Er,Cr:YSGG laser
irradiation in reducing pain and on healing rate of traumatic ulcerations (TU)
during a 2-week period after placement of new complete dentures. BACKGROUND DATA:
Denture-related TU are painful, and result in patient discomfort. Lasers are used
in the treatment of different kinds of mucosal lesions; however, there are no
published data available concerning the clinical outcome of the use of laser
therapy in the treatment of TU. MATERIALS AND METHODS: Thirty edentulous patients
with newly fabricated complete dentures who subsequently developed one or more
pairs of TU participated in this study. For each patient, ulcerations were
randomly assigned to the test and control groups. In the test group, ulcerations
were irradiated with Er,Cr:YSGG laser. In the control group, the same laser
without laser emission was used. Pain was assessed with a visual analog scale
(VAS). Healing of ulcerations (HU) was graded by a clinician. RESULTS: In the
test group, laser irradiation provided significantly reduced pain immediately
after treatment, and provided a significant healing effect 1 day after treatment,
and these effects were maintained throughout the study. In the control group,
baseline VAS scores were not statistically significant at baseline and 1 day
after treatment, and HU scores were statistically significant 3, 7, and 14 days
after treatment. Intergroup comparisons revealed that the differences in VAS and
HU scores were statistically significant for all time periods after treatment,
except for day 14. CONCLUSIONS: Based on these findings, it may be concluded that
Er,Cr:YSGG laser is effective in the treatment of TU.
PMID- 25844683
TI - Real-time local experimental monitoring of the bleaching process.
AB - OBJECTIVE: The purpose of this article was to investigate a new setup for tooth
bleaching and monitoring of the same process in real time, so to prevent
overbleaching and related sideeffects of the bleaching procedure. BACKGROUND
DATA: So far, known bleaching procedures cannot simultaneously monitor and
perform the bleaching process or provide any local control over bleaching.
MATERIALS AND METHODS: The experimental setup was developed at the Institute of
Physics, Zagreb. The setup consists of a camera, a controller, and optical
fibers. The bleaching was performed with 25% hydrogen peroxide activated by
ultraviolet light diodes, and the light for monitoring was emitted by white light
diodes. The collected light was analyzed using a red-green-blue (RGB) index. A K
type thermocouple was used for temperature measurements. Pastilles made from
hydroxylapatite powder as well as human teeth served as experimental objects.
RESULTS: Optimal bleaching time substantially varied among differently stained
specimens. To reach reference color (A1, Chromascop shade guide), measured as an
RGB index, bleaching time for pastilles ranged from 8 to >20 min, whereas for
teeth it ranged from 3.5 to >20 min. The reflected light intensity of each R, G,
and B component at the end of bleaching process (after 20 min) had increased up
to 56% of the baseline intensity. CONCLUSIONS: The presented experimental setup
provides essential information about when to stop the bleaching process to
achieve the desired optical results so that the bleaching process can be
completely responsive to the characteristics of every individual, leading to more
satisfying results.
PMID- 25844684
TI - Extraversion and the Rewarding Effects of Alcohol in a Social Context.
AB - The personality trait of extraversion has been linked to problematic drinking
patterns. Researchers have long hypothesized that such associations are
attributable to increased alcohol-reward sensitivity among extraverted
individuals, and surveys suggest that individuals high in extraversion gain
greater mood enhancement from alcohol than those low in extraversion.
Surprisingly, however, alcohol administration studies have not found individuals
high in extraversion to experience enhanced mood following alcohol consumption.
Of note, prior studies have examined extraverted participants-individuals who
self-identify as being highly social-consuming alcohol in isolation. In the
present research, we used a group drinking paradigm to examine whether
individuals high in extraversion gained greater reward from alcohol than did
those low in extraversion and, further, whether a particular social mechanism
(partners' Duchenne smiling) might underlie alcohol reward sensitivity among
extraverted individuals. Social drinkers (n 720) consumed a moderate dose of
alcohol, placebo, or control beverage in groups of 3 over the course of 36 min.
This social interaction was video-recorded, and Duchenne smiling was coded using
the Facial Action Coding System. Results indicated that participants high in
extraversion reported significantly more mood enhancement from alcohol than did
those low in extraversion. Further, mediated moderation analyses focusing on
Duchenne smiling of group members indicated that social processes fully and
uniquely accounted for alcohol reward-sensitivity among individuals high in
extraversion. Results provide initial experimental evidence that individuals high
in extraversion experience increased mood-enhancement from alcohol and further
highlight the importance of considering social processes in the etiology of
alcohol use disorder.
PMID- 25844685
TI - Malaria invasion ligand RH5 and its prime candidacy in blood-stage malaria
vaccine design.
AB - With drug resistance to available therapeutics continuing to develop against
Plasmodium falciparum malaria, the development of an effective vaccine candidate
remains a major research goal. Successful interruption of invasion of parasites
into erythrocytes during the blood stage of infection will prevent the severe
clinical symptoms and complications associated with malaria. Previously studied
blood stage antigens have highlighted the hurdles that are inherent to this life
cycle stage, namely that highly immunogenic antigens are also globally diverse,
resulting in protection only against the vaccine strain, or that naturally
acquired immunity to blood stage antigens do not always correlate with actual
protection. The blood stage antigen reticulocyte binding homolog RH5 is essential
for parasite viability, has globally limited diversity, and is associated with
protection from disease. Here we summarize available information on this invasion
ligand and recent findings that highlight its candidacy for inclusion in a blood
stage malaria vaccine.
PMID- 25844687
TI - A Handling Study to Assess Use of the Respimat((r)) Soft MistTM Inhaler in
Children Under 5 Years Old.
AB - BACKGROUND: Respimat((r)) Soft Mist(TM) Inhaler (SMI) is a hand-held device that
generates an aerosol with a high, fine-particle fraction, enabling efficient lung
deposition. The study objective was to assess inhalation success among children
using Respimat SMI, and the requirement for assistance by the parent/caregiver
and/or a valved holding chamber (VHC). METHODS: This open-label study enrolled
patients aged <5 years with respiratory disease and history of coughing and/or
recurrent wheezing. Patients inhaled from the Respimat SMI (air only; no aerosol)
using a stepwise configuration: "1" (dose released by child); "2" (dose released
by parent/caregiver), and "3" (Respimat SMI with VHC, facemask, and
parent/caregiver help). Co-primary endpoints included the ability to perform
successful inhalation as assessed by the investigators using a standardized
handling questionnaire and evaluation of the reasons for success. Inhalation
profile in the successful handling configuration was verified with a
pneumotachograph. Patient satisfaction and preferences were investigated in a
questionnaire. RESULTS: Of the children aged 4 to <5 years (n=27) and 3 to <4
years (n=30), 55.6% and 30.0%, respectively, achieved success without a VHC or
help; with assistance, another 29.6% and 10.0%, respectively, achieved success,
and the remaining children were successful with VHC. All children aged 2 to <3
years (n=20) achieved success with the Respimat SMI and VHC. Of those aged <2
years (n=22), 95.5% had successful handling of the Respimat SMI with VHC and
parent/caregiver help. Inhalation flow profiles generally confirmed the outcome
of the handling assessment by the investigators. Most parent/caregiver and/or
child respondents were satisfied with operation, instructions for use, handling,
and ease of holding the Respimat SMI with or without a VHC. CONCLUSIONS: The
Respimat SMI is suitable for children aged <5 years; however, children aged <5
years are advised to add a VHC to complement its use.
PMID- 25844688
TI - Amelioration of bleomycin-induced pulmonary fibrosis in a mouse model by a
combination therapy of bosentan and imatinib.
AB - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is characterized by alveolitis,
progressing into fibrosis. Due to the involvement of both endothelin and platelet
derived growth factor signaling in IPF, combination effects of a bosentan and
imatinib were studied in mouse model of bleomycin-induced pulmonary fibrosis.
METHODS: Mice subjected to bleomycin instillation (0.05 U) and were administered
with either bosentan (100 mg/kg) and/or imatinib (50 mg/kg). Inflammatory cell
count, total protein estimation in bronchoalveolar lavage fluid, lung edema,
superoxide dismutase, catalase, myeloperoxidase activities, and Hematoxylin &
Eosin staining were performed on day 7. Hydroxyproline content, alpha-smooth
muscle actin (SMA), collagens I and III gene expression analysis,
immunohistochemistry, matrix metalloproteinases-9 and -2 activities, trichrome
and sirius red staining were performed on day 21. RESULTS: Combination treatment
with bosentan and imatinib prevented bleomycin-induced mortality and loss of body
weight more than the individual agents. On day 7, the combination therapy
attenuated bleomycin-induced increase of total and differential inflammatory cell
counts, total proteins, lung wet/dry weight ratio, myeloperoxidase activity, lung
inflammatory cell infiltration more than individual agents alone. Bosentan but
not imatinib ameliorated superoxide dismutase and catalase activities, which were
lowered following bleomycin instillation. On day 21, combination therapy
ameliorated bleomycin-induced increase of fibrosis score, collagen deposition,
protein and gene expression of SMA, mRNA levels of collagens-I and -III, matrix
metalloproteinase-9 and -2 activities more than monotherapy. CONCLUSION:
Combination of bosentan and imatinib exerted more enhanced protection against
bleomycin-induced inflammation and fibrosis than either of the agents alone.
PMID- 25844686
TI - Circuit resistance training attenuates acute exertion-induced reductions in
arterial function but not inflammation in obese women.
AB - BACKGROUND: Cardiovascular disease (CVD) is a leading cause of preventable death
among young women in the United States. Habitual resistance exercise training is
known to have beneficial effects on endothelial function and CVD risk factors,
including obesity; however, previous studies show that acute resistance exercise
impairs endothelial function in obese adults who are sedentary, a response that
may be linked to inflammation. We sought to determine if circuit-based resistance
training (CRT) attenuates acute resistance exercise-induced reductions in
endothelial function in a population of young, obese, sedentary women and whether
or not inflammation plays a role in this response. METHODS: Eighteen obese [body
mass index (BMI) 30.0-40.0 kg . m(-2)] young premenopausal women were randomly
assigned to either a CRT group or a no-exercise control group (CON). Conduit
artery endothelial function was assessed using brachial artery flow-mediated
dilation (FMD) determined by ultrasound before and after a single bout of
strenuous weightlifting (SWL). In addition, circulating inflammatory mediators
(tumor necrosis factor-alpha and C-reactive protein), blood pressure, fasting
blood lipids, glucose, waist circumference, body composition, and aerobic
capacity were assessed. RESULTS: Among participants randomized to the CRT group,
8 weeks of training led to considerable increases in FMD after SWL (P=0.001)
compared to the CON group. However, no significant differences between the groups
were observed in circulating inflammatory mediators, blood pressure, fasting
blood lipids, or other physical and physiological characteristics. CONCLUSIONS:
This study shows that CRT alleviates acute exertion-induced reductions in
endothelial function among obese sedentary women in the absence of changes in
inflammation.
PMID- 25844689
TI - Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin
receptor blockade.
AB - PURPOSE/AIM: We performed a randomized, prospective animal study to investigate
whether inhibiting the renin-angiotensin system with a (pro)renin receptor
blocker (PRRB) prevents acute lung injury (ALI) in a rodent model. MATERIALS: We
used Thirty-six male Sprague-Dawley rats. We administered lipopolysaccharide
(LPS; 2 mg/kg) intratracheally with or without PRRB pretreatment (1 mg/kg/d).
METHODS: We performed bronchoalveolar lavage (BAL) and lung removal at 4 h after
LPS administration and measured levels of inflammatory cytokines, high mobility
group box 1 (HMGB-1) protein, and total protein in bronchoalveolar lavage fluid
(BALF). Myeloperoxidase (MPO) activity was detected in lung tissue homogenates
using a sensitive ELISA. We performed hematoxylin and eosin staining and
immunohistochemical staining for nonproteolytically activated prorenin in the
left lung. RESULTS: The PRRB decreased leukocyte counts and total protein, tumor
necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2, IL-6, and IL-10 levels
in the BALF and MPO activity in lung tissue. The PRRB reduced interstitial edema,
hemorrhage, and the neutrophil count in the lung tissues. Consistent with the
reduction in lung tissue damage, immunohistochemical staining showed that the
PRRB decreased the amount of nonproteolytically activated prorenin. CONCLUSIONS:
The PRRB blocked LPS-induced inflammatory response in the lung and protected
against ALI. Therefore, it is a potential therapeutic agent for preventing ALI.
PMID- 25844690
TI - Neuron-derived orphan receptor 1 promoted human pulmonary artery smooth muscle
cells proliferation.
AB - AIMS: As a transcription factor of the nuclear receptor superfamily, neuron
derived orphan receptor 1 (NOR1) is induced rapidly in response to various
extracellular stimuli. But, it is still unclear its role in pulmonary artery
smooth muscle cells proliferation. MATERIALS AND METHODS: Human PASMCs were
cultured in vitro and stimulated by serum. The special antisense
oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene
expression. Real-time PCR and Western-blot were used to evaluate the gene
expression and protein levels. RESULTS: Fetal bovine serum (FBS) induced human
PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1
gene expression in a dose dependent manner and a time dependent manner. 10% FBS
induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher
NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid
significantly promoted DNA synthesis and cells proliferation. Moreover, the
special AS-ODNs against human NOR1 not only prevented NOR1 expression but also
inhibited DNA synthesis and cells proliferation significantly. The NOR1 over
expression plasmid could up-regulate cyclin D1 expression markedly, but the AS
ODNs inhibited cyclin D1 expression significantly. CONCLUSION: So, we concluded
that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved
in this process.
PMID- 25844691
TI - Regional lung tissue changes with mechanical ventilation and fluid load.
AB - PURPOSE: To investigate the regional gravity-dependent impact of mechanical
ventilation and fluid overload on lung extracellular matrix (ECM) in healthy
lungs. MATERIALS AND METHODS: The glycosaminoglycans (GAGs) composition of the
ventral and dorsal lung parenchyma was determined in anesthetized supine healthy
rats mechanically ventilated for 4 hours in air: (a) at low (~7.5 mL/kg) or high
(~ 23 mL /kg) tidal volume (V(T)) and 0 cmH2O positive end-expiratory pressure
(PEEP); (b) at low or high V(T) at 5 cmH2O PEEP and (c) with or without 7 mL
/(kg.h) intravenous saline infusion. RESULTS: Mechanical ventilation degraded
lung ECM, with alveolar septa thinning and structural GAGs disorganization. Low
V(T) ventilation was associated with significant tissue structure changes in both
ventral and dorsal lung regions, while high VT mainly affected the dependent
ones. PEEP decreased ECM injury mainly in the ventral lung regions, although it
did not prevent matrix fragmentation and washout at high V(T). Intravascular
fluid load increased lung damage prevalently in the ventral lung regions.
CONCLUSION: Mechanical ventilation and fluid load may cause additive injuries in
healthy lungs, mainly in ventral regions.
PMID- 25844692
TI - Pulmonary edema measured by MRI correlates with late-phase response to allergen
challenge.
AB - PURPOSE: Asthma is associated with reversible airway obstruction, leucocyte
infiltration, airways hyperresponsiveness (AHR), and airways remodeling. Fluid
accumulation causes pulmonary edema contributing to airways obstruction. We
examined the temporal relationship between the late asthmatic response (LAR)
following allergen challenge of sensitized guinea-pigs and pulmonary edema
measured by magnetic resonance imaging (MRI). MATERIALS AND METHODS: Ovalbumin
(OVA) sensitized guinea-pigs received either a single OVA inhalation (acute) or
nine OVA inhalations at 48 h intervals (chronic). Airways obstruction was
measured as specific airways conductance (sG(aw)) by whole body plethysmography.
AHR to inhaled histamine and bronchoalveolar lavage for leucocyte counts were
measured 24 h after a single or the final chronic ovalbumin challenges. MRI was
performed at intervals after OVA challenge and high-intensity edemic signals were
quantified. RESULTS: Ovalbumin caused early bronchoconstriction, followed at 7 h
by an LAR and at 24 h AHR and leucocyte influx. The bright-intensity MRI edema
signal, peaking at 7 h, was significantly (P < .05) greater after chronic (9.0 +/
0.7 * 10(3) mm(3)) than acute OVA (7.6 +/- 0.2 * 10(3) mm(3)). Dexamethasone
treatment before acute OVA abolished the AHR and LAR and significantly reduced
eosinophils and the bright-intensity MRI edema from 9.1 +/- 1.0 to 6.4 +/- 0.3 *
10(3) mm(3). CONCLUSION: We show a temporal relationship between edema and the
LAR and their parallel reduction, along with eosinophils and AHR, by
dexamethasone. This suggests a close causative association between pulmonary
edema and impaired airways function.
PMID- 25844694
TI - Early Head CT Findings Are Associated With Outcomes After Pediatric Out-of
Hospital Cardiac Arrest.
AB - OBJECTIVES: Head CT after out-of-hospital cardiac arrest is often obtained to
evaluate intracranial pathology. Among children admitted to the PICU following
pediatric out-of-hospital cardiac arrest, we hypothesized that loss of gray-white
matter differentiation and basilar cistern and sulcal effacement are associated
with mortality and unfavorable neurologic outcome. DESIGN: Retrospective, cohort
study. SETTING: Single, tertiary-care center PICU. PATIENTS: Seventy-eight
patients less than 18 years old who survived out-of-hospital cardiac arrest to
PICU admission and had a head CT within 24 hours of return of spontaneous
circulation were evaluated from July 2005 through May 2012. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Median time to head CT from return of spontaneous
circulation was 3.3 hours (1.0, 6.0). Median patient age was 2.3 years (0.4,
9.5). Thirty-nine patients (50%) survived, of whom 29 (74%) had favorable
neurologic outcome. Nonsurvivors were more likely than survivors to have 1) loss
of gray-white matter differentiation (Hounsfield unit ratios, 0.96 [0.88, 1.07]
vs 1.1 [1.07, 1.2]; p < 0.001), 2) basilar cistern effacement (93% vs 7%; p =
0.001; positive predictive value, 94%; negative predictive value, 59%), and 3)
sulcal effacement (100% vs 0%; p <= 0.001; positive predictive value, 100%;
negative predictive value, 68%). All patients with poor gray-white matter
differentiation or sulcal effacement had unfavorable neurologic outcomes. Only
one patient with basilar cistern effacement had favorable outcome. CONCLUSIONS:
Loss of gray-white matter differentiation and basilar cistern effacement and
sulcal effacement are associated with poor outcome after pediatric out-of
hospital cardiac arrest. Select patients may have favorable outcomes despite
these findings.
PMID- 25844695
TI - HIV Infection and Linkage to HIV-Related Medical Care in Large Urban Areas in the
United States, 2009.
AB - BACKGROUND: Residents of urban areas have accounted for the majority of persons
diagnosed with HIV disease in the United States. Linking persons recently
diagnosed with HIV to primary medical care is an important indicator in the
National HIV/AIDS Strategy. METHODS: We analyzed data reported to the HIV
Surveillance System in 18 urban areas in the United States. Standardized
executable SAS programs were distributed to determine the number of HIV cases
living through 2008, number of HIV cases diagnosed in 2009, and the percentage of
those diagnosed in 2009 who had reported CD4 lymphocyte or HIV viral load test
results within 3 months of HIV diagnosis. Data were presented by jurisdiction,
age group at diagnosis, race/ethnicity, sex at birth, birth country, disease
stage, and transmission category. RESULTS: By jurisdiction, the percentage of
persons diagnosed in 2009 with at least 1 CD4 or HIV viral load test within 3
months of diagnosis ranged from 48.5% to 92.5% (median: 70.9). The percentage of
persons linked to care varied by age group and by racial/ethnic groups. Fourteen
of the 18 areas reported that the percentage of persons linked to care was
greater than 65%, the baseline measure indicated in the National HIV/AIDS
Strategy. CONCLUSIONS: A wide range in percent linked to HIV medical care was
observed between residents of 18 urban areas in the United States with noted age
and racial disparities. Routine testing and linkage efforts and intensified
prevention efforts should be considered to increase access to primary HIV-related
medical care.
PMID- 25844693
TI - Age influences inflammatory responses, hemodynamics, and cardiac proteasome
activation during acute lung injury.
AB - BACKGROUND: Acute lung injury (ALI) is a significant source of morbidity and
mortality in critically ill patients. Age is a major determinant of clinical
outcome in ALI. The increased ALI-associated mortality in the older population
suggests that there are age-dependent alterations in the responses to pulmonary
challenge. The objective of this observational study was to evaluate age
dependent differences in the acute (within 6 hours) immunological and
physiological responses of the heart and lung, to pulmonary challenge, that could
result in increased severity. METHODS: Male C57Bl/6 mice (young: 2-3 months, old:
18-20 months) were challenged intratracheally with cell wall components from Gram
positive bacteria (lipoteichoic acid and peptidoglycan). After 6 hours, both
biochemical and physiological consequences of the challenge were assessed.
Alveolar infiltration of inflammatory cells and protein, airspace and blood
cytokines, cardiac function and myocardial proteasome activity were determined.
RESULTS: In young mice, there was a dose-dependent response to pulmonary
challenge resulting in increased airspace neutrophil counts, lung permeability,
and concentrations of cytokines in bronchoalveolar lavage fluid and plasma. A
midrange dose was then selected to compare the responses in young and old
animals. In comparison, the old animals displayed increased neutrophil
accumulation in the airspaces, decreased arterial oxygen saturation, body
temperatures, plasma cytokine concentrations, and a lack of myocardial proteasome
response, following challenge. CONCLUSIONS: Age-dependent differences in the
onset of systemic response and in maintenance of vital functions, including
temperature control, oxygen saturation, and myocardial proteasome activation, are
evident. We believe a better understanding of these age-related consequences of
ALI can lead to more appropriate treatments in the elderly patient population.
PMID- 25844696
TI - A Population-Level Evaluation of the Effect of Antiretroviral Therapy on Cancer
Incidence in Kyadondo County, Uganda, 1999-2008.
AB - BACKGROUND: The introduction of antiretroviral therapy (ART) in the United States
and Europe has led to changes in the incidence of cancers among HIV-infected
persons, including dramatic decreases in Kaposi sarcoma and non-Hodgkin lymphoma,
and increases in Hodgkin lymphoma, liver, and anogenital malignancies. We sought
to evaluate whether increasing availability of ART is associated with changing
cancer incidence in Uganda. METHODS: Incident cases of 10 malignancies were
identified from Kampala Cancer Registry from 1999 to 2008. ART coverage rates for
Uganda were abstracted from the Joint United Nations Program on HIV/AIDS reports.
Negative binomial and Poisson regression modeled the association between ART
coverage and age-adjusted cancer incidence. RESULTS: ART coverage in Uganda
increased from 0% to 43% from 1999 to 2008. With each 10% increase in ART
coverage, incidence of Kaposi sarcoma decreased by 5% [incidence rate ratio (IRR)
= 0.95, 95% confidence interval: 0.91 to 0.99, P = 0.02] and stomach cancer
decreased by 13% [IRR = 0.87 (95% CI: 0.80 to 0.95), P = 0.002]. Conversely,
incidence of non-Hodgkin lymphoma increased by 6% [IRR = 1.06 (95% CI: 1 to
1.12), P = 0.05], liver cancer by 12% [IRR = 1.12 (95% CI: 1.04 to 1.21), P =
0.002], prostate cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.10), P = 0.05], and
breast cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.11), P = 0.05]. ART coverage was
not associated with incidence of invasive cervical cancer, lung, colon, and
Hodgkin disease. These findings were similar when restricted to histologically
confirmed cases. CONCLUSIONS: Our findings suggest that AIDS-defining
malignancies and other malignancies are likely to remain significant public
health burdens in sub-Saharan Africa even as ART availability increases.
PMID- 25844697
TI - CMV Retinitis Diagnosis by Non-ophthalmologists: Learning Curve Over a 4-Day
Training Workshop.
PMID- 25844698
TI - Metabolic Profiling of Children Undergoing Surgery for Congenital Heart Disease.
AB - OBJECTIVE: Inflammation and metabolism are closely interlinked. Both undergo
significant dysregulation following surgery for congenital heart disease,
contributing to organ failure and morbidity. In this study, we combined cytokine
and metabolic profiling to examine the effect of postoperative tight glycemic
control compared with conventional blood glucose management on metabolic and
inflammatory outcomes in children undergoing congenital heart surgery. The aim
was to evaluate changes in key metabolites following congenital heart surgery and
to examine the potential of metabolic profiling for stratifying patients in terms
of expected clinical outcomes. DESIGN: Laboratory and clinical study. SETTING:
University Hospital and Laboratory. PATIENTS: Of 28 children undergoing surgery
for congenital heart disease, 15 underwent tight glycemic control postoperatively
and 13 were treated conventionally. INTERVENTIONS: Metabolic profiling of blood
plasma was undertaken using proton nuclear magnetic resonance spectroscopy. A
panel of metabolites was measured using a curve-fitting algorithm. Inflammatory
cytokines were measured by enzyme-linked immunosorbent assay. The data were
assessed with respect to clinical markers of disease severity (Risk Adjusted
Congenital heart surgery score-1, Pediatric Logistic Organ Dysfunction, inotrope
score, duration of ventilation and pediatric ICU-free days). MEASUREMENTS AND
MAIN RESULTS: Changes in metabolic and inflammatory profiles were seen over the
time course from surgery to recovery, compared with the preoperative state. Tight
glycemic control did not significantly alter the response profile. We identified
eight metabolites (3-D-hydroxybutyrate, acetone, acetoacetate, citrate, lactate,
creatine, creatinine, and alanine) associated with surgical and disease severity.
The strength of proinflammatory response, particularly interleukin-8 and
interleukin-6 concentrations, inversely correlated with PICU-free days at 28
days. The interleukin-6/interleukin-10 ratio directly correlated with plasma
lactate. CONCLUSIONS: This is the first report on the metabolic response to
cardiac surgery in children. Using nuclear magnetic resonance to monitor the
patient journey, we identified metabolites whose concentrations and trajectory
appeared to be associated with clinical outcome. Metabolic profiling could be
useful for patient stratification and directing investigations of clinical
interventions.
PMID- 25844699
TI - Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling
Pathway.
AB - OBJECTIVES: Septic acute kidney injury is one of the most common and life
threatening complications in critically ill patients, and there is no approved
effective treatment. We have shown xenon provides renoprotection against ischemia
reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here,
we studied the effects of xenon preconditioning on septic acute kidney injury and
its mechanism. DESIGN: Experimental animal investigation. SETTING: University
research laboratory. SUBJECTS: Experiments were performed with male C57BL/6 mice,
10 weeks of age, weighing 20-25 g. INTERVENTIONS: We induced septic acute kidney
injury by a single intraperitoneal injection of Escherichia coli
lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either
70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney
injury. In vivo knockdown of miR-21 was performed using locked nucleic acid
modified anti-miR, the role of miR-21 in renal protection conferred by the xenon
preconditioning was examined, and miR-21 signaling pathways were analyzed.
MEASUREMENTS AND MAIN RESULTS: Xenon preconditioning provided morphologic and
functional renoprotection, characterized by attenuation of renal tubular damage,
apoptosis, and a reduction in inflammation. Furthermore, xenon treatment
significantly upregulated the expression of miR-21 in kidney, suppressed
proinflammatory factor programmed cell death protein 4 expression and nuclear
factor-kappaB activity, and increased interleukin-10 production. Meanwhile, xenon
preconditioning also suppressed the expression of proapoptotic protein
phosphatase and tensin homolog deleted on chromosome 10, activating protein
kinase B signaling pathway, subsequently increasing the expression of
antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of
miR-21 upregulated its target effectors programmed cell death protein 4 and
phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in
an increase in apoptosis, and exacerbated lipopolysaccharide-induced acute kidney
injury. CONCLUSION: Our findings demonstrated that xenon preconditioning
protected against lipopolysaccharide-induced acute kidney injury via activation
of miR-21 target signaling pathways.
PMID- 25844700
TI - Radial Artery Applanation Tonometry for Continuous Noninvasive Cardiac Output
Measurement: A Comparison With Intermittent Pulmonary Artery Thermodilution in
Patients After Cardiothoracic Surgery.
AB - OBJECTIVES: Radial artery applanation tonometry allows completely noninvasive
continuous cardiac output estimation. The aim of the present study was to compare
cardiac output measurements obtained with applanation tonometry (AT-CO) using the
T-Line system (Tensys Medical, San Diego, CA) with cardiac output measured by
intermittent pulmonary artery thermodilution using a pulmonary artery catheter
(PAC-CO) with regard to accuracy, precision of agreement, and trending ability.
DESIGN: A prospective method comparison study. SETTING: The study was conducted
in a cardiosurgical ICU of a German university hospital. PATIENTS: We performed
cardiac output measurements in 50 patients after cardiothoracic surgery.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three independent sets of
three consecutive thermodilution measurements (i.e., PAC-CO) each were performed
per patient, and AT-CO was measured simultaneously. The average of the three
thermodilution cardiac output measurements was compared with the average of the
corresponding three AT-CO values resulting in 150 paired cardiac output
measurements. In 13 patients, cardiac output-modifying maneuvers performed for
clinical reasons additionally allowed to evaluate trending ability. For
statistical analysis, we used Bland-Altman analysis, the percentage error, four
quadrant plot, and concordance analysis. Mean PAC-CO was 4.7 +/- 1.2 L/min and
mean AT-CO was 4.9 +/- 1.1 L/min. The mean of differences was -0.2 L/min with 95%
limits of agreement of -1.8 to + 1.4 L/min. The percentage error was 34%. The
concordance rate was 95%. CONCLUSIONS: Continuous cardiac output measurement
using the noninvasive applanation tonometry technology is basically feasible in
ICU patients after cardiothoracic surgery. The applanation tonometry technology
provides cardiac output values with reasonable accuracy and precision of
agreement compared with intermittent pulmonary artery thermodilution measurements
in a clinical study setting and is able to reliably track cardiac output changes
induced by cardiac output-modifying maneuvers.
PMID- 25844701
TI - Postoperative Functional Evaluation of Percutaneous Vertebroplasty Compared With
Percutaneous Kyphoplasty for Vertebral Compression Fractures.
AB - Both percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) have
shown their superiorities in the treatment of vertebral compression fractures
(VCFs), yet, few studies have compared their postoperative functional outcomes in
patients with VCFs; the authors therefore conducted this meta-analysis to explore
the postoperative functional recovery efficacies of PVP and PKP in the treatment
of VCFs. Computerized bibliographic databases were applied to identify relevant
articles comparing the therapeutic effect of PVP and PKP in the treatment of
VCFs. Standardized mean difference and its 95% confidence interval were
calculated. Statistical analyses were conducted with the STATA statistical
software. Postoperative Oswestry Disability Index investigation outcomes revealed
a significant difference between the PVP group and PKP group. Subgroup analysis
by the 8 dimensions of the SF-36 health survey presented a statistical
significance in general health between the PVP group and PKP group. The
application of PKP has the superiority in postoperative functional recovery of
VCFs as compared with PVP, especially in efficaciously extending kyphosis angle,
improving vertebral body height and decreasing complication rate.
PMID- 25844702
TI - In situ medical simulation investigation of emergency department procedural
sedation with randomized trial of experimental bedside clinical process guidance
intervention.
AB - INTRODUCTION: Patient safety during emergency department procedural sedation
(EDPS) can be difficult to study. Investigators sought to delineate and
experimentally assess EDPS performance and safety practices of senior-level
emergency medicine residents through in situ simulation. METHODS: Study sessions
used 2 pilot-tested EDPS scenarios with critical action checklists, institutional
forms, embedded probes, and situational awareness questionnaires. An experimental
informatics system was separately developed for bedside EDPS process guidance.
Postgraduate year 3 and 4 subjects completed both scenarios in randomized order;
only experimental subjects were provided with the experimental system during
second scenarios. RESULTS: Twenty-four residents were recruited into a control
group (n = 12; 6.2 +/- 7.4 live EDPS experience) and experimental group (n = 12;
11.3 +/- 8.2 live EDPS experience [P = 0.10]). Critical actions for EDPS
medication selection, induction, and adverse event recognition with resuscitation
were correctly performed by most subjects. Presedation evaluations, sedation
rescue preparation, equipment checks, time-outs, and documentation were
frequently missed. Time-outs and postsedation assessments increased during second
scenarios in the experimental group. Emergency department procedural sedation
safety probe detection did not change across scenarios in either group.
Situational awareness scores were 51% +/- 7% for control group and 58% +/- 12%
for experimental group. Subjects using the experimental system completed more
time-outs and scored higher Simulation EDPS Safety Composite Scores, although
without comprehensive improvements in EDPS practice or safety. CONCLUSIONS: Study
simulations delineated EDPS and assessed safety behaviors in senior emergency
medicine residents, who exhibited the requisite medical knowledge base and
procedural skill set but lacked some nontechnical skills that pertain to
emergency department microsystem functions and patient safety. The experimental
system exhibited limited impact only on in-simulation time-out compliance.
PMID- 25844703
TI - Syphilis among adolescents and young adults in Cincinnati, Ohio: testing,
infection and characteristics of youth with syphilis infection.
AB - Little is known about the epidemiology of syphilis among adolescents and young
adults. This study examined, among more than 17000 young people aged 13-22 years
old, trends in rates of syphilis testing and infection; characteristics of
infected adolescents; and agreement about syphilis staging and treatment between
provider and chart reviewer. Rates of syphilis testing increased but rates of
syphilis infection did not increase significantly over a 5-year period. A
majority of infected men reported only opposite-sex sexual contact. High
agreement between providers and chart reviewers was found. These findings
demonstrate the need for complete assessment of risk factors and use of local
epidemiology in screening practices.
PMID- 25844704
TI - Transcutaneous Electrical Nerve Stimulation Increases Rectal Activity in
Children.
AB - OBJECTIVES: Neurostimulation is increasingly used in treating bladder and bowel
dysfunction, but its effect on rectal motility is obscure. The aim of the study
was to evaluate the acute effect of transcutaneous electrical nerve stimulation
(TENS) on rectal motility in children with overactive bladder (OAB). METHODS: In
this double-blind placebo-controlled study in 20 children with OAB (mean age 8.6
+/- 1.8 years; 7 girls), 48-hour urodynamic monitoring including rectal manometry
was performed. After 24-hours of baseline investigation without stimulation the
children were randomised to either active TENS (n = 10) or placebo (n = 10).
Surface electrodes were placed over the sacral bone. The exterior of active and
placebo stimulators was identical. Starting in the morning, the children received
either continuous TENS stimulation or placebo until bedtime. Rectal contractions
were defined as pressure runs exceeding 5 cm H2O and lasting >=3 minutes.
RESULTS: At baseline there was no significant difference in proportion of time
with rectal contractions in the 2 groups (TENS group median 31% [range 12%-66%]
vs placebo group median 31% [range 10%-66%]; P = 0.75); however, on the day of
stimulation there was more time with rectal contractions in the group receiving
TENS (median 51% [range 25%-78%]) compared with placebo (median 32% [range 4%
68%]; P = 0.02). Also, there was an increase in time with rectal contractions in
the TENS group (P = 0.007) but not in the placebo group (P = 0.39). The night
after the TENS was disabled, rectal activity in both groups returned to baseline
level. CONCLUSIONS: TENS acutely increases time with rectal contractions in
children undergoing urodynamic investigation. The effect disappears when the
stimulator is turned off.
PMID- 25844706
TI - Effects of Amoxicillin and Clavulanic Acid on the Spontaneous Mechanical Activity
of Juvenile Rat Duodenum.
AB - OBJECTIVES: There are a limited number of medications for the treatment of
foregut dysmotility. Enteral amoxicillin/clavulanic acid induces phase III
duodenal contractions in a fasting pediatric patient. The mechanism by which this
occurs is unknown. We examined the individual contributions of amoxicillin and
clavulanic acid on the spontaneous mechanical activity of juvenile rat duodenum
to better understand this phenomenon. METHODS: Duodenal segments from juvenile
rats were longitudinally attached to force transducers in organ baths. Samples
were cumulatively exposed to amoxicillin or clavulanic acid. Separate samples
were exposed to carbachol alone to assess response in both the presence and
absence of amoxicillin or clavulanic acid. Basal tone, frequency, and amplitude
of contractions were digitized and recorded. RESULTS: The amplitude of the
spontaneous contractions increased with amoxicillin. Inhibition of neuronal
activity prevented this effect. Clavulanic acid did not affect the spontaneous
contractions. Basal tone and the rate of contractions did not differ with either
drug. Stimulation with carbachol in the presence of amoxicillin caused a
statistically significant increase in the contractility compared with carbachol
alone. CONCLUSIONS: Amoxicillin alters the spontaneous longitudinal mechanical
activity of juvenile rat duodenum. Our results suggest that amoxicillin modulates
the spontaneous pattern of cyclic mechanical activity of duodenal smooth muscle
through noncholinergic, neurally mediated mechanisms. Our work provides an
initial physiologic basis for the therapeutic use of amoxicillin in patients with
gastrointestinal dysmotility.
PMID- 25844707
TI - An Opinion on "Staging" of Infant Formula: A Developmental Perspective on Infant
Feeding.
AB - Breast milk is a dynamic fluid with compositional changes occurring throughout
the period of lactation. Some of these changes in nutrient concentrations reflect
the successively slowing growth rate and developmental changes in metabolic
requirements that infants undergo during the first year of life. Infant formula,
in contrast, has a static composition, intended to meet the nutritional
requirements of infants from birth to 6 or 12 months of age. To better fit the
metabolic needs of infants and to avoid nutrient limitations or excesses, we
suggest that infant formulas should change in composition with the age of the
infant, that is, different formulas are created/used for different ages during
the first year of life. We propose that specific formulas for 0 to 3 months
(stage 1), 3 to 6 months (stage 2), and 6 to 12 months (stage 3) of age may be
nutritionally and physiologically advantageous to infants. Although this
initially may impose some difficult practical/conceptual issues, we believe that
this staging concept would improve nutrition of formula-fed infants and,
ultimately, improve outcomes and make their performance more similar to that of
breast-fed infants.
PMID- 25844708
TI - Threonine Requirement of the Enterally Fed Term Infant in the First Month of
Life.
AB - OBJECTIVE: Threonine is one of the essential amino acids. Its major fate is
incorporation into intestinal mucosal proteins and synthesis of secretory
glycoproteins. Therefore, it has an important function in the neonatal gut
barrier integrity. The objective was to quantify the threonine requirement in
fully enterally fed term neonates by means of the indicator amino acid oxidation
(IAAO) method, using L-[1-C]phenylalanine as indicator. METHODS: After a 24-hour
test diet adaptation, containing randomly assigned amounts of threonine (range 5
182 mg . kg . day), the participating neonates received a primed continuous
infusion of [C]bicarbonate and L-[1-C]phenylalanine. At baseline and during the
plateau phase of both infusions, breath samples were obtained for CO2. The
fractional L-[1-C]phenylalanine oxidation (FCO2) was estimated and plotted
against the threonine intakes. Biphasic linear regression crossover analysis was
used to calculate the breakpoint of the FCO2, representing the mean threonine
requirement. Data are presented as mean +/- SD. RESULTS: Thirty-two term neonates
(gestational age 39 +/- 1 weeks, birth weight 3.3 +/- 0.3 kg, mean postnatal age
10 +/- 4 days) were studied. The mean threonine requirement was estimated to be
68 mg . kg . day with an upper and lower 95% confidence interval of 104 and 32 mg
. kg . day, respectively (r = 0.37). CONCLUSIONS: The determined threonine
requirement is extremely close to the existing requirement recommendations (~90%
of the present World Health Organization requirement guidelines). Infant formula
preparations presently on the market, however, contain up to twice as much
threonine as recommended. The threonine intake in formula-fed infants may
therefore be reduced considerably.
PMID- 25844709
TI - Safety of a New Amino Acid Formula in Infants Allergic to Cow's Milk and
Intolerant to Hydrolysates.
AB - OBJECTIVES: Amino acid-based formulas (AAFs) are recommended for children with
cow's-milk allergy (CMA) failing to respond to extensively hydrolysed formulas
(eHFs). We evaluated the effects of a new thickened AAF (TAAF, Novalac),
containing a pectin-based thickener, and a reference AAF (RAAF, Neocate) on
allergy symptoms and safety, through blood biochemistry analysis and growth.
METHODS: Infants (ages < 18 months) with CMA symptoms failing to respond to eHFs
were randomised in a double-blind manner to receive TAAF or RAAF for 3 months.
All of the infants were then fed TAAF for 3 additional months. Paediatric visits
occurred at 1, 3, and 6 months. Blood samples were collected at inclusion and 3
months. RESULTS: Results at 1 month were previously described. The 75 infants
with proven CMA and eHF intolerance tolerated their allocated formula. At 3
months, the dominant allergic symptom had disappeared in 76.2% of the infants
with TAAF and in 51.5% of the infants with RAAF (P = 0.026). The Scoring Atopic
Dermatitis Index significantly improved more with TAAF than with RAAF (-27.3 +/-
2.3 vs -20.8 +/- 2.2, P = 0.048). Of the infants, 92.9% had normal stools (soft
or formed consistency) with TAAF vs 75.8% with RAAF (P = 0.051). More infants in
TAAF group had better quality of nighttime sleep (P = 0.036) and low frequency of
irritability signs (P < 0.001). With both formulas, all of the biochemical
parameters were within normal ranges. There were no differences between the 2
groups in any of the anthropometric z scores. CONCLUSIONS: The new TAAF was
tolerated by all of the infants with CMA and intolerance to eHFs. Anthropometric
and clinical data showed that both formulas were safe.
PMID- 25844710
TI - Endoscopic Incision for the Treatment of Refractory Esophageal Anastomotic
Strictures in Children.
AB - OBJECTIVES: The aim of the present study was to assess the safety and efficacy of
endoscopic incision (EI) for the treatment of refractory anastomotic esophageal
strictures in pediatric patients. METHODS: We retrospectively reviewed the
medical records of pediatric patients with refractory anastomotic strictures
after surgical repair of esophageal atresia who underwent >=3 sessions of
endoscopic treatments (dilation and/or stenting). They were treated with EI alone
or together with esophageal stenting. Efficacy and safety were evaluated during
periodical follow-up. RESULTS: All of the 7 children received the procedure
successfully with the operation time of 15 to 60 minutes. Four of them received
EI alone, whereas the other 3 received EI with esophageal stenting (EIES). The
symptoms remitted in all of the patients, and the dysphagia score decreased from
3-4 to 0-1 during follow-up from 1 to 21 months. The average diameter of
stricture was enlarged from 3 mm (range 2-5 mm) to 10.6 mm (range 8-12 mm). One
patient suffered from chest pain, which resolved within 3 days. Patient 1 had
recurrence 11 months after EIES, and patient 6 had recurrence 3 months after EI.
They all underwent an additional EI to maintain patency. No severe complications
were observed during operation and periodical follow-up. CONCLUSIONS: EI is safe
and appears effective for refractory esophageal anastomotic strictures in
children in the short term. Large comparative studies are warranted to further
confirm our findings. The long-term follow-up is necessary for assessing the long
term efficacy of the new technique.
PMID- 25844711
TI - Importance of Physical Examination: Occult Blood and Perianal Examination in
Screening for Pediatric Inflammatory Bowel Disease.
PMID- 25844712
TI - Bile Acids as Biomarkers: Liver and Gut Cross Talk in NAFLD.
PMID- 25844714
TI - What tumours should we treat with focal therapy based on risk category, grade,
size and location?
AB - PURPOSE OF REVIEW: Focal therapy aims to reduce side-effects of active whole
gland therapies with an acceptable or noninferior oncologic benefit for the
patient. The definition of the lesion to treat using this tissue-preserving
approach is central, and there is a recent shift in considering more aggressive
disease than in the past. This article examines recent consensus reports,
assessment of emerging techniques, histologic considerations as well as results
of trials and their development. RECENT FINDINGS: Accumulation of evidence
reinforces the concept of clinically significant disease. Latest histologic
assessment studies specify the index lesion characteristics. Index lesion
localization was accurately evaluated by both multiparametric MRI (mpMRI)
targeted and transperineal mapping biopsy techniques against reference standard.
mpMRI continues its development in accurate disease stratification. Development
of new treatment modalities allows the clinician to investigate treatment of a
lesion in various zonal anatomy locations. Consensus reports establish the
intermediate risk population as the target for focal therapy, leaving very low
risk disease to surveillance. Reviews of past clinical trials, including
intermediate risk population, reveal encouraging oncologic follow-up. Ongoing
trials will test focal therapy of index lesion with surveillance of insignificant
secondary lesions. SUMMARY: Focal therapy should be investigated for intermediate
risk population, leaving very low risk to surveillance. Detection and
stratification techniques, namely mpMRI-targeted and transperineal biopsies, have
an evolving role in lesion selection to confirm encouraging oncologic benefit for
the patient.
PMID- 25844713
TI - Characterization of Porphyrin-Co(III)-'Nitrene Radical' Species Relevant in
Catalytic Nitrene Transfer Reactions.
AB - To fully characterize the Co(III)-'nitrene radical' species that are proposed as
intermediates in nitrene transfer reactions mediated by cobalt(II) porphyrins,
different combinations of cobalt(II) complexes of porphyrins and nitrene transfer
reagents were combined, and the generated species were studied using EPR, UV-vis,
IR, VCD, UHR-ESI-MS, and XANES/XAFS measurements. Reactions of cobalt(II)
porphyrins 1(P1) (P1 = meso-tetraphenylporphyrin (TPP)) and 1(P2) (P2 = 3,5
Di(t)Bu-ChenPhyrin) with organic azides 2(Ns) (NsN3), 2(Ts) (TsN3), and 2(Troc)
(TrocN3) led to the formation of mono-nitrene species 3(P1)(Ns), 3(P2)(Ts), and
3(P2)(Troc), respectively, which are best described as [Co(III)(por)(NR"(*-))]
nitrene radicals (imidyl radicals) resulting from single electron transfer from
the cobalt(II) porphyrin to the 'nitrene' moiety (Ns: R" = -SO2-p-C6H5NO2; Ts: R"
= -SO2C6H6; Troc: R" = -C(O)OCH2CCl3). Remarkably, the reaction of 1(P1) with N
nosyl iminoiodane (PhI?NNs) 4(Ns) led to the formation of a bis-nitrene species
5(P1)(Ns). This species is best described as a triple-radical complex [(por(*
))Co(III)(NR"(*-))2] containing three ligand-centered unpaired electrons: two
nitrene radicals (NR"(*-)) and one oxidized porphyrin radical (por(*-)). Thus,
the formation of the second nitrene radical involves another intramolecular one
electron transfer to the "nitrene" moiety, but now from the porphyrin ring
instead of the metal center. Interestingly, this bis-nitrene species is observed
only on reacting 4(Ns) with 1(P1). Reaction of the more bulky 1(P2) with 4(Ns)
results again in formation of mainly mono-nitrene species 3(P2)(Ns) according to
EPR and ESI-MS spectroscopic studies. The mono- and bis-nitrene species were
initially expected to be five- and six-coordinate species, respectively, but
XANES data revealed that both mono- and bis-nitrene species are six-coordinate
O(h) species. The nature of the sixth ligand bound to cobalt(III) in the mono
nitrene case remains elusive, but some plausible candidates are NH3, NH2(-),
NsNH(-), and OH(-); NsNH(-) being the most plausible. Conversion of mono-nitrene
species 3(P1)(Ns) into bis-nitrene species 5(P1)(Ns) upon reaction with 4(Ns) was
demonstrated. Solutions containing 3(P1)(Ns) and 5(P1)(Ns) proved to be still
active in catalytic aziridination of styrene, consistent with their proposed key
involvement in nitrene transfer reactions mediated by cobalt(II) porphyrins.
PMID- 25844716
TI - Introduction to a series of articles that focus on methane.
PMID- 25844717
TI - Mind wandering and selective attention to the external world.
AB - From a cognitive neuroscience perspective, the study of attention has long
centered on characterizing the basic systems we have in our brains for selecting
what external sensory information to channel to our higher level, capacity
limited processes in cortex. Less understood is how these attentional systems ebb
and flow in their selectivity over seconds to minutes in the course of pursuing
our daily activities. Toward illuminating this issue, here we review a recent
series of studies we have conducted demonstrating that the degree to which our
selective attention systems are engaged with the external environment is
coordinated over these timescales such that they collectively engage and
disengage together as a means of transiently modulating the depth of our
cognitive investment in external sensory inputs. Although our studies have
primarily focused on mind wandering in healthy, young participants, we suggest
that people's ability to comprehensively attenuate their selective attention to
the outside world plays a fundamental role in both normal human cognition and its
clinical pathology.
PMID- 25844719
TI - Sexist games=sexist gamers? A longitudinal study on the relationship between
video game use and sexist attitudes.
AB - From the oversexualized characters in fighting games, such as Dead or Alive or
Ninja Gaiden, to the overuse of the damsel in distress trope in popular titles,
such as the Super Mario series, the under- and misrepresentation of females in
video games has been well documented in several content analyses. Cultivation
theory suggests that long-term exposure to media content can affect perceptions
of social realities in a way that they become more similar to the representations
in the media and, in turn, impact one's beliefs and attitudes. Previous studies
on video games and cultivation have often been cross-sectional or experimental,
and the limited longitudinal work in this area has only considered time intervals
of up to 1 month. Additionally, previous work in this area has focused on the
effects of violent content and relied on self-selected or convenience samples
composed mostly of adolescents or college students. Enlisting a 3 year
longitudinal design, the present study assessed the relationship between video
game use and sexist attitudes, using data from a representative sample of German
players aged 14 and older (N=824). Controlling for age and education, it was
found that sexist attitudes--measured with a brief scale assessing beliefs about
gender roles in society--were not related to the amount of daily video game use
or preference for specific genres for both female and male players. Implications
for research on sexism in video games and cultivation effects of video games in
general are discussed.
PMID- 25844718
TI - Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1
infected subjects.
AB - Cross-reactive peptides on HIV-1 and FIV p24 protein sequences were studied using
peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected long-term
survivors (LTS; >10 y of infection without antiretroviral therapy, ART), short
term HIV-1 infected subjects not on ART, and ART-treated HIV-1 infected subjects.
IFNgamma-ELISpot and CFSE-proliferation analyses were performed with PBMC using
overlapping HIV-1 and FIV p24 peptides. Over half of the HIV-1 infected subjects
tested (22/31 or 71%) responded to one or more FIV p24 peptide pools by either
IFNgamma or T-cell proliferation analysis. PBMC and T cells from infected
subjects in all 3 HIV(+) groups predominantly recognized one FIV p24 peptide pool
(Fp14) by IFNgamma production and one additional FIV p24 peptide pool (Fp9) by T
cell proliferation analysis. Furthermore, evaluation of overlapping SIV p24
peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of
SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9. The responses to these FIV
peptide pools were highly reproducible and persisted throughout 2-4 y of
monitoring. Intracellular staining analysis for cytotoxins and phenotyping for
CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic
T lymphocyte-associated molecules including perforin, granzyme B, granzyme A,
and/or expression of CD107a. Selected FIV and corresponding SIV epitopes
recognized by HIV-1 infected patients indicate that these protein sequences are
evolutionarily conserved on both SIV and HIV-1 (e.g., Hp15:Fp14:Sp14). These
studies demonstrate that comparative immunogenicity analysis of HIV-1, FIV, and
SIV can identify evolutionarily-conserved T cell-associated lentiviral epitopes,
which could be used as a vaccine for prophylaxis or immunotherapy.
PMID- 25844721
TI - Back to basics: an audit of measurement of infant growth at presentation to
hospital.
AB - OBJECTIVES: Infants who present or are admitted to hospital with illness or with
inadequate growth and development are those most at risk of decreased nutritional
status. However, not all infants who present or are admitted to hospital have
their growth assessed. The aim of the present study was to identify how
frequently anthropometric measurements were documented in charts of infants
presenting and/or admitted to a tertiary paediatric hospital. METHODS: A
systematic random sample of hospital charts of infants who had presented to the
emergency department between 1 July 2011 and 30 June 2012 was audited
retrospectively for the presence of appropriate documentation of measurement.
RESULTS: In all, 465 charts were audited, representing 10% of infants who
presented to the emergency department in the year. The frequency of
anthropometric measures was: birthweight 103 (22%), presentation weight 275
(59%), length 8 (2%), head circumference 15 (3%), percentiles 27 (6%) and body
mass index score 1 (0%). Age of the infant was significantly associated with
recording of birthweight. There were no significant relationships found between
gender, socioeconomic status, gestational age, delivery type and recording of
diagnosis and birthweight. CONCLUSIONS: Infant measurements were not recorded on
many occasions. Assessment of growth as a marker of illness or nutritional
deficit has been poorly assessed in this group. This is a missed opportunity to
assess infant growth in this population, which has been found to be at risk of
decreased nutritional status. Identification and treatment of growth deficits are
a cost-effective method of optimising infant health worldwide.
PMID- 25844720
TI - Inducible but not constitutive expression of PD-L1 in human melanoma cells is
dependent on activation of NF-kappaB.
AB - Monoclonal antibodies against immune checkpoint blockade have proven to be a
major success in the treatment of melanoma. The programmed death receptor-1
ligand-1 (PD-L1) expression on melanoma cells is believed to have an inhibitory
effect on T cell responses and to be an important escape mechanism from immune
attack. Previous studies have shown that PD-L1 can be expressed constitutively or
can be induced by IFN-gamma secreted by infiltrating lymphocytes. In the present
study we have investigated the mechanism underlying these two modes of PD-L1
expression in melanoma cells including cells that had acquired resistance to the
BRAF inhibitor vemurafenib. PD-L1 expression was examined by flow cytometry and
immunoblotting. Specific inhibitors and siRNA knockdown approaches were used to
examine the roles of the RAF/ MEK, PI3K, NF-kappaB, STAT3 and AP1/ c-Jun
pathways. IFN-gamma inducible expression of PD-L1 was dependent on NF-kappaB as
shown by inhibition with BMS-345541, an inhibitor of IkappaB and the BET protein
inhibitor I-BET151, as well as by siRNA knockdown of NF-kappaB subunits. We were
unable to implicate the BRAF/MEK pathway as major regulators in PD-L1 expression
on vemurafenib resistant cells. Similarly the PI3K/AKT pathway and the
transcription factors STAT3 and c-Jun had only minor roles in IFN-gamma induced
expression of PD-L1. The mechanism underlying constitutive expression remains
unresolved. We suggest these results have significance in selection of treatments
that can be used in combination with monoclonal antibodies against PD1, to
enhance their effectiveness and to reduce inhibitory effects melanoma cells have
against cytotoxic T cell activity.
PMID- 25844723
TI - Pattern of paediatric dermatoses at dermatology clinics in Ile-Ife and Ilesha,
Nigeria.
AB - BACKGROUND: In developing countries, skin diseases are one of the most common
causes of morbidity. AIM: A prospective descriptive study was conducted to
determine the pattern of skin diseases in childhood and adolescents presenting to
the outpatient dermatology clinics of Obafemi Awolowo University Teaching
Hospitals Complex at Ile-Ife and Ilesha, Osun State. METHODS: Patients aged 2
weeks to 19 years attending the clinics between October 2009 and September 2012
were included. RESULTS: A total of 491 dermatoses were recorded in 441 patients.
There were 244 (49.6%) males. Dermatophyte infections (17.1%), papular urticaria
(6.7%), atopic dermatitis (6.3%), vitiligo (5.3%), acne (4.7%) and viral warts
(3.7%) were the most frequent dermatoses. Skin infections and infestations,
mostly dermatophyte infections and viral warts, accounted for 57.6% of the skin
conditions. Of the non-infectious diseases, papular urticaria and atopic
dermatitis were the most common. Dermatophyte infections were the most prevalent
in children (25.8%), and acne vulgaris in adolescents (11.8%). CONCLUSION: Skin
infections and infestations, mostly dermatophyte infections, were the most
prevalent in children, and acne vulgaris in adolescents.
PMID- 25844724
TI - Development of new assays for Epstein-Barr and porcine epidemic diarrhea viruses.
PMID- 25844725
TI - Cognition and Quality-of-Life Outcomes in the Targeted Temperature Management
Trial for Cardiac Arrest.
PMID- 25844722
TI - Signs analysis and clinical assessment: phase-contrast computed tomography of
human breast tumours.
AB - PURPOSE: To analyse the diagnostic signs present in slices of human breast tumour
specimens using synchrotron radiation phase-contrast imaging computed tomography
(PCI-CT) for the first time and assess the feasibility of this technique for
clinical applications. MATERIALS AND METHODS: The ethics committee of our
university and relevant clinical hospital approved this prospective study, and
written informed consent was obtained from all patients. PCI-CT of human breast
tumour specimens with synchrotron radiation was performed at the Shanghai
Synchrotron Radiation Facility (SSRF). A total of 14 specimens of early-stage
carcinomas and 8 specimens of adenomas were enrolled. Based on raw data
reconstruction, the diagnostic signs present in the slices were analysed and
correlated with histopathology. We proposed a criterion for clinical diagnosis
according to the evaluated signs and the Breast Imaging Reporting and Data System
(BI-RADS) for reference. The criterion was then assessed by clinicians in a
double-blind method. Finally, descriptive statistics were evaluated, depending on
the assessment results. RESULTS: The 14 carcinoma specimens and 8 adenoma
specimens were diagnosed as malignant and benign tumours, respectively. The total
coincidence rate was 100%. CONCLUSION: Our study results demonstrate that the X
ray diagnostic signs observed in the specimen slices and the criterion used for
clinical diagnosis were accurate and reliable. The criterion based on signs
analysis can be used to differentiate early-stage benign or malignant tumours. As
a promising imaging method, PCI-CT can serve as a possible and feasible
supplement to BI-RADS in the future.
PMID- 25844726
TI - What is the right number of clinic appointments?: Visit frequency and the
accountable care organization.
PMID- 25844727
TI - The Future of the National Children's Study.
PMID- 25844728
TI - Understanding how institutional culture affects attending physicians' and
trainees' resuscitation discussions.
PMID- 25844729
TI - The Stabilizing Role of the Intramolecular C-H...O Hydrogen Bond in Cyclic Amides
Derived From alpha-Methylbenzylamine.
AB - A series of five-, six-, seven-, and eight-membered lactams containing the chiral
auxiliary alpha-methylbenzylamine were structurally analyzed and further studied
by DFT calculations with the purpose to examine with detail the previously
detected intramolecular C-H...O hydrogen-bonding interaction formed between the
hydrogen atom of the alpha-methylbenzylamine and the carbonyl group of the cyclic
amide. The main objective was to establish whether its presence does have a
tangible relevance in their spatial arrangement in solution and in the solid
state or is a simple and not stabilizing interaction.
PMID- 25844731
TI - Enhanced Electroresponsive Performance of Double-Shell SiO2/TiO2 Hollow
Nanoparticles.
AB - The double-shell SiO2/TiO2 hollow nanoparticles (DS HNPs) are successfully
fabricated and adopted as dispersing materials for electrorheological (ER) fluids
to investigate an influence of shell structure on ER properties. The DS HNPs
based ER fluid exhibits outstanding ER performance which is 4.1-fold higher
compared to that of single shell SiO2/TiO2 hollow nanoparticles (SS HNPs)-based
ER fluid. The significantly improved ER property of DS HNPs-based ER fluid is
ascribed to the enhanced interfacial polarization. In addition, the ER activities
of DS HNPs-based ER fluids are examined depending on the particle diameter. The
yield stress of DS HNPs-based ER fluids increases up to 302.4 kPa under an
electric field of 3 kV mm(-1) by reducing the particle size, which is remarkable
performance enough to promise sufficient probability for practical and industrial
applications. The enhanced ER performance of the smaller DS HNPs is attributed to
the increased surface area of large pores (30-35 nm) within the shells, resulting
in a large achievable polarizability determined by dielectric constants.
Furthermore, the antisedimentation property is analyzed in order to offer an
additional insight into the effect of particle size on the ER fluids.
PMID- 25844730
TI - Leisure time physical activity and mortality: a detailed pooled analysis of the
dose-response relationship.
AB - IMPORTANCE: The 2008 Physical Activity Guidelines for Americans recommended a
minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5
metabolic-equivalent hours per week) of aerobic activity for substantial health
benefit and suggested additional benefits by doing more than double this amount.
However, the upper limit of longevity benefit or possible harm with more physical
activity is unclear. OBJECTIVE: To quantify the dose-response association between
leisure time physical activity and mortality and define the upper limit of
benefit or harm associated with increased levels of physical activity. DESIGN,
SETTING, AND PARTICIPANTS: We pooled data from 6 studies in the National Cancer
Institute Cohort Consortium (baseline 1992-2003). Population-based prospective
cohorts in the United States and Europe with self-reported physical activity were
analyzed in 2014. A total of 661,137 men and women (median age, 62 years; range,
21-98 years) and 116,686 deaths were included. We used Cox proportional hazards
regression with cohort stratification to generate multivariable-adjusted hazard
ratios (HRs) and 95% CIs. Median follow-up time was 14.2 years. EXPOSURES:
Leisure time moderate- to vigorous-intensity physical activity. MAIN OUTCOMES AND
MEASURES: The upper limit of mortality benefit from high levels of leisure time
physical activity. RESULTS: Compared with individuals reporting no leisure time
physical activity, we observed a 20% lower mortality risk among those performing
less than the recommended minimum of 7.5 metabolic-equivalent hours per week (HR,
0.80 [95% CI, 0.78-0.82]), a 31% lower risk at 1 to 2 times the recommended
minimum (HR, 0.69 [95% CI, 0.67-0.70]), and a 37% lower risk at 2 to 3 times the
minimum (HR, 0.63 [95% CI, 0.62-0.65]). An upper threshold for mortality benefit
occurred at 3 to 5 times the physical activity recommendation (HR, 0.61 [95% CI,
0.59-0.62]); however, compared with the recommended minimum, the additional
benefit was modest (31% vs 39%). There was no evidence of harm at 10 or more
times the recommended minimum (HR, 0.69 [95% CI, 0.59-0.78]). A similar dose
response relationship was observed for mortality due to cardiovascular disease
and to cancer. CONCLUSIONS AND RELEVANCE: Meeting the 2008 Physical Activity
Guidelines for Americans minimum by either moderate- or vigorous-intensity
activities was associated with nearly the maximum longevity benefit. We observed
a benefit threshold at approximately 3 to 5 times the recommended leisure time
physical activity minimum and no excess risk at 10 or more times the minimum. In
regard to mortality, health care professionals should encourage inactive adults
to perform leisure time physical activity and do not need to discourage adults
who already participate in high-activity levels.
PMID- 25844734
TI - Adjunctive diagnostic procedures for percutaneous coronary intervention.
PMID- 25844735
TI - Improving physician well-being.
PMID- 25844736
TI - Improving physician well-being.
PMID- 25844737
TI - Improving physician well-being--reply.
PMID- 25844738
TI - Sex-specific chest pain characteristics.
PMID- 25844739
TI - Effect of wine consumption on mortality.
PMID- 25844740
TI - Sex-specific chest pain characteristics--reply.
PMID- 25844741
TI - Evaluating clinical management decisions by recent graduates in the era of high
value, cost-conscious care.
PMID- 25844742
TI - Effect of wine consumption on mortality--reply.
PMID- 25844743
TI - Evaluating clinical management decisions by recent graduates in the era of high
value, cost-conscious care--reply.
PMID- 25844744
TI - For deep vein thrombosis, follow the randomized trials.
PMID- 25844745
TI - For deep vein thrombosis, follow the randomized trials--reply.
PMID- 25844746
TI - Metrics for evaluating the quality of handovers.
PMID- 25844747
TI - What ecologic analyses cannot tell us about medical marijuana legalization and
opioid pain medication mortality.
PMID- 25844748
TI - Metrics for evaluating the quality of handovers--reply.
PMID- 25844749
TI - What ecologic analyses cannot tell us about medical marijuana legalization and
opioid pain medication mortality--reply.
PMID- 25844750
TI - Concern about the use of venlafaxine to treat vasomotor symptoms.
PMID- 25844751
TI - beta-Blockers in diabetic patients with heart failure.
PMID- 25844752
TI - beta-Blockers in diabetic patients with heart failure--reply.
PMID- 25844753
TI - Concern about the use of venlafaxine to treat vasomotor symptoms--reply.
PMID- 25844754
TI - Error in methods.
PMID- 25844755
TI - Error in figures.
PMID- 25844756
TI - Lurasidone in the treatment of bipolar depression with mixed (subsyndromal
hypomanic) features: post hoc analysis of a randomized placebo-controlled trial.
AB - OBJECTIVE: Mixed (subsyndromal hypomanic) features are prevalent in patients with
bipolar depression and are associated with more severe and complex illness,
including increased risk for suicide attempts, higher switch to mania during
antidepressant therapy, and a higher rate of recurrence. The aim of this post hoc
analysis was to evaluate the efficacy and safety of lurasidone in the treatment
of patients with bipolar depression presenting with mixed features. METHOD:
Patients with a DSM-IV-TR diagnosis of major depressive episode associated with
bipolar I disorder, with or without rapid cycling, and with a Montgomery-Asberg
Depression Rating Scale (MADRS) score >= 20 and a Young Mania Rating Scale (YMRS)
score <= 12 were randomly assigned to 6 weeks of double-blind, once-daily
treatment with lurasidone 20-60 mg, lurasidone 80-120 mg, or placebo. The
presence of mixed features was defined as a YMRS score >= 4 at study baseline.
Efficacy analyses included change in MADRS total score from baseline to week 6
(the primary outcome in the original study, conducted between April 2009 and
February 2012). RESULTS: At baseline, mixed features were present in 56% of
patients (lurasidone, n = 182/323; placebo, n = 90/162). Treatment with
lurasidone (vs placebo) was associated with significantly greater reductions in
MADRS scores in the mixed features group (-15.7 vs -10.9; P = .001; week 6; mixed
model for repeated measures [MMRM]; effect size, 0.48) and in the group without
mixed features (-15.2 vs -10.8; P = .002; week 6; MMRM; effect size, 0.48). Rates
of protocol-defined treatment-emergent hypomania or mania were similar for
patients with mixed features (lurasidone, 2.2%; placebo, 3.2%) and without mixed
features (lurasidone, 3.4%; placebo, 0.0%). CONCLUSIONS: Lurasidone was found in
this post hoc analysis to be efficacious in the treatment of patients with
bipolar depression who present with mixed features (assessed cross-sectionally at
study baseline). No increased risk of treatment-emergent mania was observed in
either group. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00868699.
PMID- 25844757
TI - Aluminum plasmonic multicolor meta-hologram.
AB - We report a phase-modulated multicolor meta-hologram (MCMH) that is polarization
dependent and capable of producing images in three primary colors. The MCMH
structure is made of aluminum nanorods that are arranged in a two-dimensional
array of pixels with surface plasmon resonances in red, green, and blue. The
aluminum nanorod array is patterned on a 30 nm thick SiO2 spacer layer sputtered
on top of a 130 nm thick aluminum mirror. With proper design of the structure, we
obtain resonances of narrow bandwidths to allow for implementation of the
multicolor scheme. Taking into account of the wavelength dependence of the
diffraction angle, we can project images to specific locations with predetermined
size and order. With tuning of aluminum nanorod size, we demonstrate that the
image color can be continuously varied across the visible spectrum.
PMID- 25844758
TI - Kidney-type glutaminase (GLS1) is a biomarker for pathologic diagnosis and
prognosis of hepatocellular carcinoma.
AB - The lack of sensitive and specific biomarkers hinders pathological diagnosis and
prognosis for hepatocellular carcinoma (HCC). Since glutaminolysis plays a
crucial role in carcinogenesis and progression, we sought to determine if the
expression of kidney-type and liver-type glutaminases (GLS1 and GLS2) were
informative for pathological diagnosis and prognosis of HCC. We compared the
expression of GLS1 and GLS2 in a large set of clinical samples including HCC,
normal liver, and other liver diseases. We found that GLS1 was highly expressed
in HCC; whereas, expression of GLS2 was mainly confined to non-tumor hepatocytes.
The sensitivity and specificity of GLS1 for HCC were 96.51% and 75.21%,
respectively. A metabolic switch from GLS2 to GLS1 was observed in a series of
tissues representing progressive pathologic states mimicking HCC oncogenic
transformation, including normal liver, fibrotic liver, dysplasia nodule, and
HCC. We found that high expression of GLS1 and low expression of GLS2 in HCC
correlated with survival time of HCC patients. Expression of GLS1 and GLS2 were
independent indexes for survival time; however, prognosis was predominantly
determined by the level of GLS1 expression. These findings indicate that GLS1
expression is a sensitive and specific biomarker for pathological diagnosis and
prognosis of HCC.
PMID- 25844759
TI - History of Mechanical Ventilation. From Vesalius to Ventilator-induced Lung
Injury.
AB - Mechanical ventilation is a life-saving therapy that catalyzed the development of
modern intensive care units. The origins of modern mechanical ventilation can be
traced back about five centuries to the seminal work of Andreas Vesalius. This
article is a short history of mechanical ventilation, tracing its origins over
the centuries to the present day. One of the great advances in ventilatory
support over the past few decades has been the development of lung-protective
ventilatory strategies, based on our understanding of the iatrogenic consequences
of mechanical ventilation such as ventilator-induced lung injury. These
strategies have markedly improved clinical outcomes in patients with respiratory
failure.
PMID- 25844761
TI - Surface pressure and microstructure of carbon nanotubes at an air-water
interface.
AB - This article reports the surface pressure and microstructure of two different
types of carbon nanotubes (CNTs) at an air-water interface; namely, as-produced
CNTs (nf-CNTs) and CNTs functionalized with carboxyl groups (f-CNTs). Both types
of CNTs formed 3D aggregates upon compression using a Langmuir-Pockels trough.
However, f-CNTs showed a lower degree of aggregation compared with that of nf
CNTs. This is attributed to the deprotonation of the carboxyl groups within the
water subphase, leading to additional electrostatic repulsion between f-CNTs. For
the same initial amount of CNTs spread onto the interface, the actual coverage of
f-CNTs was higher than that of nf-CNTs at a given trough area. At high
compression, f-CNTs formed aligned CNT domains at the interface. These 2D domains
resembled 3D liquid-crystalline structures formed by excluded volume
interactions. The denser packing and orientational ordering of f-CNTs also
contributed to a compressional modulus higher than that of nf-CNTs, as calculated
from the surface pressure isotherms. A Volmer equation of state was applied to
model the measured surface pressure containing both thermodynamic and mechanical
contributions. The Volmer model, however, did not consider the loss of CNTs from
the interface due to 3D aggregation and consequently overestimated the surface
pressure at high compression. The actual coverage of CNT during compression was
back calculated from the model and was in agreement with the value obtained
independently from optical micrographs. The findings of this work may have a
broader impact on understanding the assembly and collective behavior of rod-like
particles with a high aspect ratio at an air-water interface.
PMID- 25844760
TI - Tetrahydroindazoles as Interleukin-2 Inducible T-Cell Kinase Inhibitors. Part II.
Second-Generation Analogues with Enhanced Potency, Selectivity, and
Pharmacodynamic Modulation in Vivo.
AB - The medicinal chemistry community has directed considerable efforts toward the
discovery of selective inhibitors of interleukin-2 inducible T-cell kinase (ITK),
given its role in T-cell signaling downstream of the T-cell receptor (TCR) and
the implications of this target for inflammatory disorders such as asthma. We
have previously disclosed a structure- and property-guided lead optimization
effort which resulted in the discovery of a new series of tetrahydroindazole
containing selective ITK inhibitors. Herein we disclose further optimization of
this series that resulted in further potency improvements, reduced off-target
receptor binding liabilities, and reduced cytotoxicity. Specifically, we have
identified a correlation between the basicity of solubilizing elements in the ITK
inhibitors and off-target antiproliferative effects, which was exploited to
reduce cytotoxicity while maintaining kinase selectivity. Optimized analogues
were shown to reduce IL-2 and IL-13 production in vivo following oral or
intraperitoneal dosing in mice.
PMID- 25844764
TI - Here comes the sun--is vitamin D a cure for all that ails us?
PMID- 25844763
TI - Commentary: Launch of a quality improvement network for evidence-based management
of uncommon pediatric endocrine disorders: Turner syndrome as a prototype.
AB - BACKGROUND: Traditional, hypothesis-oriented research approaches have thus far
failed to generate sufficient evidence to achieve consensus about the management
of children with many endocrine disorders, partly because of the rarity of these
disorders and because of regulatory burdens unique to research in children.
OBJECTIVE: The Pediatric Endocrine Society is launching a quality improvement
network in spring 2015 for the management of pediatric endocrine disorders that
are relatively uncommon in any single practice and/or for which there is no
consensus on management. DESIGN: The first of the quality improvement programs to
be implemented seeks to improve the care of 11- to 17-year-old girls with Turner
syndrome who require initiation of estrogen replacement therapy by providing a
standardized clinical assessment and management plan (SCAMP) for transdermal
estradiol treatment to induce pubertal development. The SCAMP algorithm
represents a starting point within current best practice that is meant to undergo
refinement through an iterative process of analysis of deidentified data
collected in the course of clinical care by a network of pediatric
endocrinologists. CONCLUSION: It is anticipated that this program will not only
improve care, but will also result in actionable data that will generate new
research hypotheses and changes in management of pediatric endocrine disorders.
PMID- 25844765
TI - Making it real--the environmental burden of disease. What does it take to make
people pay attention to the environment and health?
PMID- 25844767
TI - Erratum.
PMID- 25844766
TI - Corrigenda.
PMID- 25844770
TI - Letter to the editor: Per-operative hemodynamic instability in normotensive
patients with incidentally discovered pheochromocytomas.
PMID- 25844771
TI - Response to the letter by Gaujoux S., et al.
PMID- 25844772
TI - Letter to the editor: Treatment of Paget's disease in patients with renal
impairment.
PMID- 25844773
TI - Response to the letter by Asik M., et al.
PMID- 25844774
TI - Methodologically sound: Evaluating the psychometric approach to the assessment of
human life history [reply to Copping, Campbell, and Muncer, 2014].
AB - Copping, Campbell, and Muncer (2014) have recently published an article critical
of the psychometric approach to the assessment of life history (LH) strategy.
Their purported goal was testing for the convergent validation and examining the
psychometric structure of the High-K Strategy Scale (HKSS). As much of the
literature on the psychometrics of human LH during the past decade or so has
emanated from our research laboratory and those of close collaborators, we have
prepared this detailed response. Our response is organized into four main
sections: (1) A review of psychometric methods for the assessment of human LH
strategy, expounding upon the essence of our approach; (2) our
theoretical/conceptual concerns regarding the critique, addressing the broader
issues raised by the critique regarding the latent and hierarchical structure of
LH strategy; (3) our statistical/methodological concerns regarding the critique,
examining the validity and persuasiveness of the empirical case made specifically
against the HKSS; and (4) our recommendations for future research that we think
might be helpful in closing the gap between the psychometric and biometric
approaches to measurement in this area. Clearly stating our theoretical
positions, describing our existing body of work, and acknowledging their
limitations should assist future researchers in planning and implementing more
informed and prudent empirical research that will synthesize the psychometric
approach to the assessment of LH strategy with complementary methods.
PMID- 25844775
TI - Modeling the relationship between family home environment factors and parental
health.
AB - INTRODUCTION: Understanding parental health is an important part of understanding
family health. Previous research suggests that family meals, familial
relationship satisfaction, and family physical activity may separately be related
to physical health. METHOD: The current study aims to combine these variables
into a structural equation model to determine the collective relationship they
have with adult health within a sample of parents (n = 1,435). Most parents were
married, White, and highly educated. RESULTS: The relationship between family
meals and parental health was significant (beta = -.07, t = -2.29, p < .05), with
the full model having adequate fit and accounting for some of the overall
variance in parental health. Familial relationship satisfaction and family
physical activity were not found to be associated with parental health.
Exploratory findings of the sample stratified by biological sex are described.
DISCUSSION: Findings from the current study were consistent with a systemic
perspective in that parents may have health benefits when they participate in
family-level behavior (e.g., family meals). Additional areas for research and
limitations to the current study are also discussed.
PMID- 25844776
TI - Please break the silence: Parents' views on communication between pediatric
primary care and mental health providers.
AB - INTRODUCTION: The purpose of this study was to gain a better understanding of
parents' preferences regarding the sharing of information between their
children's primary care and mental health providers. METHOD: Fifty-five parents
with a child who was actively engaged in mental health treatment completed an
anonymous survey while accompanying their child to either a primary care or
mental health clinic appointment. This brief measure elicited parents'
experiences with and preferences for treatment coordination across their
children's primary care and mental health providers, with a focus on
communication practices. RESULTS: Parents consistently described communication
among their children's primary care and mental health providers as important, yet
frequently reported that such communication was not currently taking place.
Further, parents reported that they were often called upon to act as
"communication bridges" between professionals caring for their children.
DISCUSSION: Implications for the collaborative pediatric and mental health care
of children as well as recommendations for improving communication between mental
health and pediatric providers are discussed.
PMID- 25844777
TI - Spontaneous activity in the precuneus predicts individual differences in verbal
fluency in cognitively normal elderly.
AB - OBJECTIVE: The precuneus is 1 of the major cortical hubs and plays an important
role in normal aging and verbal fluency processing. The main aim of present study
was to investigate how intrinsic brain activity in the precuneus at rest predicts
individual differences in verbal fluency ability among elderly adults. METHOD:
Regional amplitude of low-frequency fluctuations (ALFF) analysis and a
correlation-based functional connectivity (FC) approach were used to analyze data
acquired from 101 cognitively normal elderly. RESULTS: ALFF in the precuneus
declined with normal aging and was significantly correlated with individual
differences in performance on the verbal fluency test (VFT). Specifically, ALFF
in the precuneus was reduced in elderly with high fluency (HF) ability compared
with those with low fluency (LF) ability. In addition, the HF individuals
displayed increased functional connectivity of the precuneus with the lateral
temporal area and prefrontal lobe, including the inferior frontal, medial
frontal, superior temporal, middle temporal, and superior frontal gyri.
CONCLUSION: Spontaneous activity in the precuneus could predict individual
differences in verbal fluency processing. Our results suggest that spontaneous
activity in the precuneus is an indicator of aging-related changes in semantic
verbal fluency processing, or even a potential biomarker for the early detection
of semantic verbal fluency deterioration.
PMID- 25844778
TI - First refusal.
PMID- 25844779
TI - What's eating you? Cutaneous larva migrans.
AB - This article provides a focused update and clinical review on cutaneous larva
migrans (CLM), including atypical clinical presentations and newer management
recommendations. The results and recommendations are subject to modification
based on future studies.
PMID- 25844780
TI - Update on pediatric psoriasis.
AB - Pediatric psoriasis accounts for approximately one-third of all cases of
psoriasis. Although pediatric psoriasis was always understood to be a chronic
inflammatory dermatosis, recent data suggest that pediatric psoriasis, similar to
its adult equivalent, is part of a generalized inflammatory diathesis associated
with metabolic syndrome, including obesity/overweight status,
hypertriglyceridemia, high blood pressure, and insulin resistance. Given the
recent proliferation of data demonstrating the generalized inflammatory nature of
psoriasis, a new emphasis on adopting a healthier lifestyle and weight control as
well as systemic therapies has emerged in the literature. This article briefly
reviews selected studies published in the last 2 years that are pertinent to
pediatric psoriasis.
PMID- 25844781
TI - New systemic therapies for psoriasis.
AB - Over the last decade, expanded understanding of psoriasis pathogenesis has led to
the development of new systemic agents such as biological drugs that have
revolutionized the treatment of psoriasis. Small molecule inhibitors also have
been studied and offer patients options for oral administration. This article
reviews recently approved and in-the-pipeline biologics (IL-17 inhibitors and IL
23 blockers) as well as small molecule inhibitors (phosphodiesterase 4 [PDE4] and
Janus kinase [Jak] inhibitors).
PMID- 25844782
TI - Disease burden and quality of life in psoriasis patients with and without
comorbid psoriatic arthritis: results from National Psoriasis Foundation panel
surveys.
AB - The comorbidity profile and overall disease impact are not well understood in
psoriasis with and without comorbid psoriatic arthritis (PsA). The objective of
this study was to compare disease characteristics, comorbidities, and psoriasis
related quality of life (QOL) in patients with moderate to severe psoriasis with
and without comorbid PsA using results from National Psoriasis Foundation (NPF)
surveys. The study included 3395 and 2072 patients with psoriasis alone and
psoriasis with PsA, respectively. The results showed the burden of psoriasis
either independently or with comorbid PsA. As severity of psoriasis increased,
patient health and QOL were found to decline.
PMID- 25844783
TI - Onchocerciasis.
PMID- 25844784
TI - What is your diagnosis? Extramammary Paget disease.
PMID- 25844785
TI - Novel psoriasis therapies and patient outcomes, part 1: topical medications.
AB - In recent years, advances in our understanding of inflammatory mediators and the
underlying pathogenesis of psoriasis and psoriatic arthritis have shed light on
potential therapeutic targets, which has led to the development of several new
promising treatments. In this article, key clinical trials, mechanisms of action,
patient outcomes, and relevant safety information for these novel topical
medications will be evaluated. This article is the first in a 3-part series on
treatments presently in the pipeline for the management of psoriasis and
psoriatic arthritis including topical agents, biologic treatments, and systemic
therapies in phase 2 and phase 3 clinical trials. With novel approaches to the
disease process, these therapies may afford more targeted individualized
treatment regimens and offer hope to patients with psoriasis and psoriatic
arthritis who have reported a suboptimal therapeutic response to conventional
therapies.
PMID- 25844786
TI - Subcutaneous sarcoidosis on ultrasonography.
PMID- 25844787
TI - Bluish red verrucous lesions on the leg.
PMID- 25844788
TI - Inability to grow long hair: a presentation of trichorrhexis nodosa.
PMID- 25844789
TI - Plasmapheresis in refractory pemphigus vulgaris: revisiting an old treatment
modality used in synchrony with pulse cyclophosphamide.
PMID- 25844790
TI - A case of Morfan syndrome.
PMID- 25844791
TI - Trigeminal trophic syndrome with histopathologic correlation.
AB - We present the case of a 49-year-old woman with trigeminal trophic syndrome
(TTS), also known as trophic trigeminal neuralgia, trigeminal neurotrophic
ulceration, and/or trigeminal neuropathy with nasal ulceration. Our case
represents an uncommon report of intractable itching and chronic pain associated
with TTS. Emphasis was placed on skin biopsy histology, which revealed no
neuronal innervation of the affected scalp despite reports of intractable itching
and chronic pain. Trigeminal trophic syndrome of the V1 branch of the trigeminal
nerve secondary to herpes zoster (HZ) with correlated histology is described.
This article provides a discussion of TTS and correlated histology as well as a
brief discussion of intractable itching and postherpetic neuralgia.
PMID- 25844792
TI - Glatiramer acetate-induced lobular panniculitis and skin necrosis.
AB - Glatiramer acetate (GA) is a drug that commonly is used for the treatment of
relapsing-remitting multiple sclerosis (RRMS). Although it typically is known as
a safe and effective therapy, a number of adverse effects associated with GA have
been reported in the literature. Local injection-site reactions (LISRs) and mild
systemic symptoms are among the most commonly described adverse effects. A review
of the literature revealed limited reports of panniculitis as an adverse effect
of GA injection and even fewer describing associated skin necrosis. We report a
case of GA-induced panniculitis and skin necrosis and discuss the occurrence of
panniculitis, necrosis, and lipoatrophy following GA injections.
PMID- 25844794
TI - Fellowships after dermatology residency: the traditional and beyond.
AB - Postresidency fellowship training options exist for graduating dermatology
residents. Formal subspecialty fellowship programs are offered in
dermatopathology, pediatric dermatology, micrographic surgery and dermatologic
oncology (procedural dermatology), and cosmetic dermatologic surgery. There also
are a number of fellowships offered at certain institutions for those interested
in more specific subspecialties or academia. This guide serves to assist
dermatology residents in learning more about fellowship opportunities.
PMID- 25844793
TI - Identification of cutaneous warts: cryotherapy-induced acetowhitelike epithelium.
PMID- 25844795
TI - Telangiectases on the cheeks and nose.
PMID- 25844796
TI - Friable nodule on the back.
PMID- 25844797
TI - Abscisic Acid Acts as a Blocker of the Bitter Taste G Protein-Coupled Receptor
T2R4.
AB - Bitter taste receptors (T2Rs) belong to the G protein-coupled receptor
superfamily. In humans, 25 T2Rs mediate bitter taste sensation. In addition to
the oral cavity, T2Rs are expressed in many extraoral tissues, including the
central nervous system, respiratory system, and reproductive system. To
understand the mechanistic roles of the T2Rs in oral and extraoral tissues, novel
blockers or antagonists are urgently needed. Recently, we elucidated the binding
pocket of T2R4 for its agonist quinine, and an antagonist and inhibitory
neurotransmitter, gamma-aminobutyric acid. This structure-function information
about T2R4 led us to screen the plant hormone abscisic acid (ABA), its precursor
(xanthoxin), and catabolite phaseic acid for their ability to bind and activate
or inhibit T2R4. Molecular docking studies followed by functional assays
involving calcium imaging confirmed that ABA is an antagonist with an IC50 value
of 34.4 +/- 1.1 MUM. However, ABA precursor xanthoxin acts as an agonist on T2R4.
Interestingly, molecular model-guided site-directed mutagenesis suggests that the
T2R4 residues involved in quinine binding are also predominantly involved in
binding to the novel antagonist, ABA. The antagonist ability of ABA was tested
using another T2R4 agonist, yohimbine. Our results suggest that ABA does not
inhibit yohimbine-induced T2R4 activity. The discovery of natural bitter blockers
has immense nutraceutical and physiological significance and will help in
dissecting the T2R molecular pathways in various tissues.
PMID- 25844798
TI - Electrochemical DNA Biosensor Based on a Tetrahedral Nanostructure Probe for the
Detection of Avian Influenza A (H7N9) Virus.
AB - A DNA tetrahedral nanostructure-based electrochemical biosensor was developed to
detect avian influenza A (H7N9) virus through recognizing a fragment of the
hemagglutinin gene sequence. The DNA tetrahedral probe was immobilized onto a
gold electrode surface based on self-assembly between three thiolated nucleotide
sequences and a longer nucleotide sequence containing complementary DNA to
hybridize with the target single-stranded (ss)DNA. The captured target sequence
was hybridized with a biotinylated-ssDNA oligonucleotide as a detection probe,
and then avidin-horseradish peroxidase was introduced to produce an amperometric
signal through the interaction with 3,3',5,5'-tetramethylbenzidine substrate. The
target ssDNA was obtained by asymmetric polymerase chain reaction (PCR) of the
cDNA template, reversely transcribed from the viral lysate of influenza A (H7N9)
virus in throat swabs. The results showed that this electrochemical biosensor
could specifically recognize the target DNA fragment of influenza A (H7N9) virus
from other types of influenza viruses, such as influenza A (H1N1) and (H3N2)
viruses, and even from single-base mismatches of oligonucleotides. Its detection
limit could reach a magnitude of 100 fM for target nucleotide sequences.
Moreover, the cycle number of the asymmetric PCR could be reduced below three
with the electrochemical biosensor still distinguishing the target sequence from
the negative control. To the best of our knowledge, this is the first report of
the detection of target DNA from clinical samples using a tetrahedral DNA probe
functionalized electrochemical biosensor. It displays that the DNA tetrahedra has
a great potential application as a probe of the electrochemical biosensor to
detect avian influenza A (H7N9) virus and other pathogens at the gene level,
which will potentially aid the prevention and control of the disease caused by
such pathogens.
PMID- 25844799
TI - Correction to multifunctional rare-earth vanadate nanoparticles: luminescent
labels, oxidant sensors, and MRI contrast agents.
PMID- 25844800
TI - Pillar cuvettes: capillary-filled, microliter quartz cuvettes with microscale
path lengths for optical spectroscopy.
AB - The goal of most analytical techniques is to reduce the lower limit of detection;
however, it is sometimes necessary to do the opposite. High sample concentrations
or samples with high molar absorptivity (e.g., dyes and metal complexes) often
require multiple dilution steps or laborious sample preparation prior to
spectroscopic analysis. Here, we demonstrate dilution-free, one-step UV-vis
spectroscopic analysis of high concentrations of platinum(IV) hexachloride in a
micropillar array, that is, "pillar cuvette". The cuvette is spontaneously filled
by wicking of the liquid sample into the micropillar array. The pillar height
(thus, the film thickness) defines the optical path length, which was reduced to
between 10 and 20 MUm in this study (3 orders of magnitude smaller than in a
typical cuvette). Only one small droplet (~2 MUL) of sample is required, and the
dispensed volume need not be precise or even known to the analyst for accurate
spectroscopy measurements. For opaque pillars, we show that absorbance is
linearly related to platinum concentration (the Beer-Lambert Law). For fully
transparent or semitransparent pillars, the measured absorbance was successfully
corrected for the fractional surface coverage of the pillars and the
transmittance of the pillars and reference. Thus, both opaque and transparent
pillars can be applied to absorbance spectroscopy of high absorptivity,
microliter samples. It is also shown here that the pillar array has a useful
secondary function as an integrated (in-cuvette) filter for particulates. For
pillar cuvette measurements of platinum solutions spiked with 6 MUm diameter
polystyrene spheres, filtered and unfiltered samples gave identical spectra.
PMID- 25844801
TI - Dilemma of sewage sludge treatment and disposal in China.
PMID- 25844802
TI - "Clickable" Polymeric Nanofibers through Hydrophilic-Hydrophobic Balance:
Fabrication of Robust Biomolecular Immobilization Platforms.
AB - Fabrication of hydrophilic polymeric nanofibers that undergo facile and selective
functionalization through metal catalyst-free Diels-Alder "click" reaction in
aqueous environment is outlined. Electrospinning of copolymers containing an
electron-rich furan moiety, hydrophobic methyl methacrylate units and hydrophilic
poly(ethylene glycol)s as side chains provide specifically functionalizable yet
antibiofouling fibers that remain stable in aqueous media due to appropriate
hydrophobic hydrophilic balance. Efficient functionalization of these nanofibers
is accomplished through the Diels-Alder reaction by exposing them to maleimide
containing molecules and ligands. Diels-Alder conjugation based functionalization
is demonstrated through attachment of fluorescein-maleimide and a maleimide
tethered biotin ligand. Biotinylated nanofibers were utilized to mediate
immobilization of the protein streptavidin, as well as streptavidin coated
quantum dots. Facile fabrication from readily available polymers and their
effective functionalization under mild and reagent-free conditions in aqueous
media make these "clickable" nanofibers attractive candidates as functionalizable
scaffolds for various biomedical applications.
PMID- 25844803
TI - Minimal conductance-based model of auditory coincidence detector neurons.
AB - Sound localization is a fundamental sensory function of a wide variety of
animals. The interaural time difference (ITD), an important cue for sound
localization, is computed in the auditory brainstem. In our previous modeling
study, we introduced a two-compartment Hodgkin-Huxley type model to investigate
how cellular and synaptic specializations may contribute to precise ITD
computation of the barn owl's auditory coincidence detector neuron. Although our
model successfully reproduced fundamental physiological properties observed in
vivo, it was unsuitable for mathematical analyses and large scale simulations
because of a number of nonlinear variables. In the present study, we reduce our
former model into three types of conductance-based integrate-and-fire (IF)
models. We test their electrophysiological properties using data from published
in vivo and in vitro studies. Their robustness to parameter changes and
computational efficiencies are also examined. Our numerical results suggest that
the single-compartment active IF model is superior to other reduced models in
terms of physiological reproducibility and computational performance. This model
will allow future theoretical studies that use more rigorous mathematical
analysis and network simulations.
PMID- 25844804
TI - Colors for molecular masses: fusion of spectroscopy and mass spectrometry for
identification of biomolecules.
AB - We present an approach that integrates ultraviolet (UV) photofragmentation
spectroscopy of cold ions with high-resolution Orbitrap mass spectrometry (MS)
and uses mathematical analysis of the recorded 2D data arrays for structural
identification of biomolecules. The synergy of the two orthogonal techniques
makes these arrays unique fingerprints of molecular ions, enabling their reliable
identifications. Using preliminary created libraries of fingerprints, the UV-MS
approach was successfully applied for quantitative identification of exact
isobaric molecules in their mixtures, which is one of the challenging cases for
mass spectrometry. We also demonstrate how the UV and fragmentation mass spectra
of unknown chemical components of a mixture can be recovered from its fingerprint
even without a use of library.
PMID- 25844805
TI - Differential interactions of gelatin nanoparticles with the major lipids of model
lung surfactant: changes in the lateral membrane organization.
AB - There has been an increasing interest in the potential of nanomedicine,
particularly in the use of nanoparticles between 10 nm and 1 MUm in diameter as
drug delivery vehicles. For pulmonary drug delivery, it is important to
understand the effect of polymeric nanoparticles on the lung surfactant in order
to optimize the carriers by reducing their potential toxicological effects. This
work presents a biophysical study of the impact of gelatin nanoparticles on
packing and lateral organization of simple and complex lipid layers containing
the major components of lung surfactant. Zwitterionic phosphatidylcholines,
negatively charged phosphatidylglycerols, and the sterol cholesterol were
employed in the models. In addition, the impact of acyl chain length was
investigated. Packing was determined by surface pressure-area isotherms, whereas
direct imaging of the surfactant at the air-water interface was performed using
Brewster angle microscopy. Our results indicate minor changes in the surface
pressure-area isotherms but concomitantly significant effects on the lateral
organization of the monolayers upon nanoparticle addition. The data also suggest
differential interactions of nanoparticles with the major lipid classes. Gelatin
nanoparticles interact stronger with negatively charged phosphatidyl-glycerols
compared to zwitterionic phosphatidyl-cholines. Furthermore, charge distribution
depending on the molar lipid ratio and acyl chain saturation is important as
well. Even cholesterol, whose concentration is low compared to other components,
plays an important role in nanoparticle interactions.
PMID- 25844806
TI - Flexible lab-tailored cut-offs for suitability of formalin-fixed tumor samples
for diagnostic mutational analyses.
AB - The selection of proper tissues from formalin-fixed and paraffin-embedded tumors
before diagnostic molecular testing is responsibility of the pathologist and
represents a crucial step to produce reliable test results. The international
guidelines suggest two cut-offs, one for the percentage and one for the number of
tumor cells, in order to enrich the tumor content before DNA extraction. The aim
of the present work was two-fold: to evaluate to what extent a low percentage or
absolute number of tumor cells can be qualified for somatic mutation testing; and
to determine how assay sensitivities can guide pathologists towards a better
definition of morphology-based adequacy cut-offs. We tested 1797 tumor specimens
from melanomas, colorectal and lung adenocarcinomas. Respectively, their BRAF, K
RAS and EGFR genes were analyzed at specific exons by mutation-enriched PCR,
pyrosequencing, direct sequencing and real-time PCR methods. We demonstrate that
poorly cellular specimens do not modify the frequency distribution of either
mutated or wild-type DNA samples nor that of specific mutations. This observation
suggests that currently recommended cut-offs for adequacy of specimens to be
processed for molecular assays seem to be too much stringent in a laboratory
context that performs highly sensitive routine analytical methods. In conclusion,
new cut-offs are needed based on test sensitivities and documented tumor
heterogeneity.
PMID- 25844807
TI - Highly Cyclable Lithium-Sulfur Batteries with a Dual-Type Sulfur Cathode and a
Lithiated Si/SiOx Nanosphere Anode.
AB - Lithium-sulfur batteries could become an excellent alternative to replace the
currently used lithium-ion batteries due to their higher energy density and lower
production cost; however, commercialization of lithium-sulfur batteries has so
far been limited due to the cyclability problems associated with both the sulfur
cathode and the lithium-metal anode. Herein, we demonstrate a highly reliable
lithium-sulfur battery showing cycle performance comparable to that of lithium
ion batteries; our design uses a highly reversible dual-type sulfur cathode
(solid sulfur electrode and polysulfide catholyte) and a lithiated Si/SiOx
nanosphere anode. Our lithium-sulfur cell shows superior battery performance in
terms of high specific capacity, excellent charge-discharge efficiency, and
remarkable cycle life, delivering a specific capacity of ~750 mAh g(-1) over 500
cycles (85% of the initial capacity). These promising behaviors may arise from a
synergistic effect of the enhanced electrochemical performance of the newly
designed anode and the optimized layout of the cathode.
PMID- 25844808
TI - Dose-dependent effects of morphine exposure on mRNA and microRNA (miR) expression
in hippocampus of stressed neonatal mice.
AB - Morphine is used to sedate critically ill infants to treat painful or stressful
conditions associated with intensive care. Whether neonatal morphine exposure
affects microRNA (miR) expression and thereby alters mRNA regulation is unknown.
We tested the hypothesis that repeated morphine treatment in stress-exposed
neonatal mice alters hippocampal mRNA and miR expression. C57BL/6 male mice were
treated from postnatal day (P) 5 to P9 with morphine sulfate at 2 or 5 mg/kg ip
twice daily and then exposed to stress consisting of hypoxia (100% N2 1 min and
100% O2 5 min) followed by 2h maternal separation. Control mice were untreated
and dam-reared. mRNA and miR expression profiling was performed on hippocampal
tissues at P9. Overall, 2 and 5 mg/kg morphine treatment altered expression of a
total of 150 transcripts (>1.5 fold change, P<0.05) from which 100 unique mRNAs
were recognized (21 genes were up- and 79 genes were down-regulated), and 5 mg/kg
morphine affected 63 mRNAs exclusively. The most upregulated mRNAs were fidgetin,
arginine vasopressin, and resistin-like alpha, and the most down-regulated were
defensin beta 11, aquaporin 1, calmodulin-like 4, chloride intracellular channel
6, and claudin 2. Gene Set Enrichment Analysis revealed that morphine treatment
affected pathways related to cell cycle, membrane function, signaling,
metabolism, cell death, transcriptional regulation, and immune response. Morphine
decreased expression of miR-204-5p, miR-455-3p, miR-448-5p, and miR-574-3p. Nine
morphine-responsive mRNAs that are involved in neurodevelopment,
neurotransmission, and inflammation are predicted targets of the aforementioned
differentially expressed miRs. These data establish that morphine produces dose
dependent changes in both hippocampal mRNA and miR expression in stressed
neonatal mice. If permanent, morphine-mediated neuroepigenetic effects may affect
long-term hippocampal function, and this provides a mechanism for the neonatal
morphine-related impairment of adult learning.
PMID- 25844810
TI - Improving environmental risk assessment of human pharmaceuticals.
AB - This paper presents 10 recommendations for improving the European Medicines
Agency's guidance for environmental risk assessment of human pharmaceutical
products. The recommendations are based on up-to-date, available science in
combination with experiences from other chemical frameworks such as the REACH
legislation for industrial chemicals. The recommendations concern: expanding the
scope of the current guideline; requirements to assess the risk for development
of antibiotic resistance; jointly performed assessments; refinement of the test
proposal; mixture toxicity assessments on active pharmaceutical ingredients with
similar modes of action; use of all available ecotoxicity studies; mandatory
reviews; increased transparency; inclusion of emission data from production; and
a risk management option. We believe that implementation of our recommendations
would strengthen the protection of the environment and be beneficial to society.
Legislation and guidance documents need to be updated at regular intervals in
order to incorporate new knowledge from the scientific community. This is
particularly important for regulatory documents concerning pharmaceuticals in the
environment since this is a research field that has been growing substantially in
the last decades.
PMID- 25844809
TI - MET gene copy number alterations and expression of MET and hepatocyte growth
factor are potential biomarkers in angiosarcomas and undifferentiated pleomorphic
sarcomas.
AB - Soft tissue sarcomas are a heterogeneous group of tumors with many different
subtypes. In 2014 an estimated 12,020 newly diagnosed cases and 4,740 soft tissue
sarcoma related deaths can be expected in the United States. Many soft tissue
sarcomas are associated with poor prognosis and therapeutic options are often
limited. The evolution of precision medicine has not yet fully reached the
clinical treatment of sarcomas since therapeutically tractable genetic changes
have not been comprehensively studied so far. We analyzed a total of 484 adult
type malignant mesenchymal tumors by MET fluorescence in situ hybridization and
MET and hepatocyte growth factor immunohistochemistry. Eleven different entities
were included, among them the most common and clinically relevant subtypes and
tumors with specific translocations or complex genetic changes. MET protein
expression was observed in 2.6% of the cases, all of which were either
undifferentiated pleomorphic sarcomas or angiosarcomas, showing positivity rates
of 14% and 17%, respectively. 6% of the tumors showed hepatocyte growth factor
overexpression, mainly seen in undifferentiated pleomorphic sarcomas and
angiosarcomas, but also in clear cell sarcomas, malignant peripheral nerve sheath
tumors, leiomyosarcomas and gastrointestinal stromal tumors. MET and hepatocyte
growth factor overexpression were significantly correlated and may suggest an
autocrine activation in these tumors. MET FISH amplification and copy number gain
were present in 4% of the tumors (15/413). Two samples, both undifferentiated
pleomorphic sarcomas, fulfilled the criteria for high level amplification of MET,
one undifferentiated pleomorphic sarcoma reached an intermediate level copy
number gain, and 12 samples of different subtypes were categorized as low level
copy number gains for MET. Our findings indicate that angiosarcomas and
undifferentiated pleomorphic sarcomas rather than other frequent adult-type
sarcomas should be enrolled in screening programs for clinical trials with MET
inhibitors. The screening methods should include both in situ hybridization and
immunohistochemistry.
PMID- 25844811
TI - Getting the message across: outcomes and risk profiles by awareness levels of the
"measure-up" obesity prevention campaign in Australia.
AB - BACKGROUND: Obesity campaign evaluations have used campaign awareness to assess
impact, yet have not compared unprompted campaign recallers, with prompted
recallers and those with no campaign recall. Using data from an Australian mass
media obesity prevention campaign linking waist circumference and chronic disease
we examined whether those with different degrees of campaign recall are distinct
groups demographically and for subsequent campaign effects. METHODS: A national
cross-sectional telephone survey of randomly selected adults aged 18 to 65 years
was conducted post- campaign (n = 2812) covering campaign recall, self-reported
diet and physical activity (PA) and waist-measuring knowledge, behaviours and
intentions to make lifestyle changes. Respondents were divided into three groups
indicating campaign recall: Unprompted Recallers (n=1154); Prompted Recallers
(n=1284); and No Recallers (n=374) and compared on demographic, knowledge, and
behavioural risk factors for obesity/chronic disease. RESULTS: Unprompted
Recallers were more likely to speak English at home (p<.001), be in the primary
campaign target group (25-45 years with children) (p<0.001) than the other two
groups and to be university educated and female than the Prompted Recall group
only (p=0.001). Unprompted Recallers had better knowledge about recommended waist
circumference (p<.001), fruit (p=0.004), vegetable (p<0.001) and PA guidelines
(p<0.001) than both the other groups. The No Recall group was less likely than
the other two to be overweight/obese (46% vs 55%, p=0.020 and 54%, p=0.037),
comparable on meeting fruit consumption and PA guidelines but more likely to meet
vegetable intake recommendations (than Unprompted Recallers only). CONCLUSIONS:
Unprompted recallers were more knowledgeable about campaign messages; behaviour
change and intentions to change were stronger for the two recall groups compared
with the No Recall group but not different between them. The current analysis
revealed subtle differences in campaign exposure and/or attendance by different
demographic subgroups that would not be apparent in a simple aware/unaware
dichotomy.
PMID- 25844812
TI - Internet sex-seeking is inconsistently linked with sexual risk in men who have
sex with men: systematic review of within-subjects comparisons.
AB - Background Internet sex-seeking has been associated at the person level with
sexual risk. However, the most robust method of encounter-level inference to
determine associations between internet sex-seeking and sexual risk is to compare
encounters against each other. We systematically reviewed within-subjects
comparisons of sexual encounters that tested associations between internet sex
seeking and sexual risk in men who have sex with men. METHODS: We systematically
searched databases on 9 July 2013, then screened records and full-text articles
in duplicate and independently. Studies were synthesised narratively. RESULTS:
Four studies were included. Although studies were generally of high quality, the
findings were inconsistent and did not show clear evidence of a relationship
between internet sex-seeking and sexual risk. CONCLUSIONS: Further research in
internet sex-seeking among men who have sex with men is required, particularly as
internet-enabled sexual sociality continues to evolve. Internet-based health
promotion may wish to target person-level features instead of encounter-specific
characteristics.
PMID- 25844813
TI - Simple analytical expression for the peak-frequency shifts of plasmonic
resonances for sensing.
AB - We derive a closed-form expression that accurately predicts the peak frequency
shift and broadening induced by tiny perturbations of plasmonic nanoresonators
without critically relying on repeated electrodynamic simulations of the spectral
response of nanoresonator for various locations, sizes, or shapes of the
perturbing objects. In comparison with other approaches of the same kind, the
force of the present approach is that the derivation is supported by a
mathematical formalism based on a rigorous normalization of the resonance modes
of nanoresonators consisting of lossy and dispersive materials. Accordingly,
accurate predictions are obtained for a large range of nanoparticle shapes and
sizes used in various plasmonic nanosensors even beyond the quasistatic limit.
The expression gives quantitative insight and, combined with an open-source code,
provides accurate and fast predictions that are ideally suited for preliminary
designs or for interpretation of experimental data. It is also valid for photonic
resonators with large mode volumes.
PMID- 25844814
TI - Distinct role of hydration water in protein misfolding and aggregation revealed
by fluctuating thermodynamics analysis.
AB - Protein aggregation in aqueous cellular environments is linked to diverse human
diseases. Protein aggregation proceeds through a multistep process initiated by
conformational transitions, called protein misfolding, of monomer species toward
aggregation-prone structures. Various forms of aggregate species are generated
through the association of misfolded monomers including soluble oligomers and
amyloid fibrils. Elucidating the molecular mechanisms and driving forces involved
in the misfolding and subsequent association has been a central issue for
understanding and preventing protein aggregation diseases such as Alzheimer's,
Parkinson's, and type II diabetes. In this Account, we provide a thermodynamic
perspective of the misfolding and aggregation of the amyloid-beta (Abeta) protein
implicated in Alzheimer's disease through the application of fluctuating
thermodynamics. This approach "dissects" the conventional thermodynamic
characterization of the end states into the one of the fluctuating processes
connecting them, and enables one to analyze variations in the thermodynamic
functions that occur during the course of protein conformational changes. The
central quantity in this approach is the solvent-averaged effective energy, f =
Eu + Gsolv, comprising the protein potential energy (Eu) and the solvation free
energy (Gsolv), whose time variation reflects the protein dynamics on the free
energy landscape. Protein configurational entropy is quantified by the magnitude
of fluctuations in f. We find that misfolding of the Abeta monomer when released
from a membrane environment to an aqueous phase is driven by favorable changes in
protein potential energy and configurational entropy, but it is also accompanied
by an unfavorable increase in solvation free energy. The subsequent dimerization
of the misfolded Abeta monomers occurs in two steps. The first step, where two
widely separated monomers come into contact distance, is driven by water-mediated
attraction, that is, by a decrease in solvation free energy, harnessing the
monomer solvation free energy earned during the misfolding. The second step,
where a compact dimer structure is formed, is driven by direct protein-protein
interactions, but again it is accompanied by an increase in solvation free
energy. The increased solvation free energy of the dimer will function as the
driving force to recruit another Abeta protein in the approach stage of
subsequent oligomerizations. The fluctuating thermodynamics analysis of the
misfolding and dimerization of the Abeta protein indicates that the interaction
of the protein with surrounding water plays a critical role in protein
aggregation. Such a water-centric perspective is further corroborated by
demonstrating that, for a large number of Abeta mutants and mutants of other
protein systems, the change in the experimental aggregation propensity upon
mutation has a significant correlation with the protein solvation free energy
change. We also find striking discrimination between the positively and
negatively charged residues on the protein surface by surrounding water
molecules, which is shown to play a crucial role in determining the protein
aggregation propensity. We argue that the protein total charge dictates such
striking behavior of the surrounding water molecules. Our results provide new
insights for understanding and predicting the protein aggregation propensity,
thereby offering novel design principles for producing aggregation-resistant
proteins for biotherapeutics.
PMID- 25844816
TI - Cavitands incorporating a Lewis acid dinickel chelate function as receptors for
halide anions.
AB - The halide binding properties of the cavitand [Ni2(L(Me2H4))](2+) (4) are
reported. Cavitand 4 exhibits a chelating N3Ni(MU-S)2NiN3 moiety with two square
pyramidal Ni(II)N3S2 units situated in an anion binding pocket of ~4 A diameter
formed by the organic backbone of the (L(Me2H4))(2-) macrocycle. The receptor
reacts with fluoride, chloride (in MeCN/MeOH), and bromide (in MeCN) ions to
afford an isostructural series of halogenido-bridged complexes [Ni2(L(Me2H4))(MU
Hal)](+) (Hal = F(-) (5), Cl(-) (6), and Br(-) (7)) featuring a N3Ni(MU-S)2(MU
Hal)NiN3 core structure. No reaction occurs with iodide or other polyatomic
anions (ClO4(-), NO3(-), HCO3(-), H2PO4(-), HSO4(-), SO4(2-)). The binding events
are accompanied by discrete UV-vis spectral changes, due to a switch of the
coordination geometry from square-pyramidal (N3S2 donor set in 4) to octahedral
in the halogenido-bridged complexes (N3S2Hal donor environment in 5-7). In
MeCN/MeOH (1/1 v/v) the log K11 values for the 1:1 complexes are 7.77(9) (F(-)),
4.06(7) (Cl(-)), and 2.0(1) (Br(-)). X-ray crystallographic analyses for
4(ClO4)2, 4(I)2, 5(F), 6(ClO4), and 7(Br) and computational studies reveal a
significant increase of the intramolecular distance between two propylene groups
at the cavity entrance upon going from F(-) to I(-) (for the DFT computed
structure). In case of the receptor 4 and fluorido-bridged complex 5, the
corresponding distances are nearly identical. This indicates a high degree of
preorganization of the [Ni2(L(Me2H4))](2+) receptor and a size fit mismatch of
the receptor binding cavity for anions larger than F(-).
PMID- 25844815
TI - Determining particulate matter and black carbon exfiltration estimates for
traditional cookstove use in rural Nepalese village households.
AB - A majority of black carbon (BC) emitted to the atmosphere in the Indo-Gangetic
Plain (IGP) region is from burning biomass fuel used in traditional, open-design
cookstoves. However, BC and particulate matter (PM) household emissions are not
well characterized. Household emission information is needed to develop emission
profiles to validate regional climate change models and serve as a baseline for
assessing the impact of adopting improved stove technology. This paper presents
field-based household PM and BC exfiltration (amount exiting) estimates from
village homes in rural Nepal that utilize traditional, open-design cookstoves.
Use of these stoves resulted in a 26% mean PM exfiltration, ranging from 6% to
58%. This is a significant departure from an 80% estimate cited in previous
reports. Furthermore, having a window/door resulted in an 11% increase in
exfiltration when an opening was present, while fuel type had a marginally
significant impact on emission. Air-exchange rates (AER) were determined with
average (95% CI) AER of 12 (10-14) per hour, consistent with previous studies. In
addition, BC to PM2.5 mass-ratio composition during cooking was ascertained, with
an average (95% CI) of 31% (24-39), agreeing with previous biomass fuel emission
composition literature.
PMID- 25844817
TI - Cowpox Helped Against Smallpox; Will the Goat Lentivirus (Caprine Arthritis
Encephalitis Virus) Help Against HIV-1?
PMID- 25844818
TI - A multicenter, open-label, Phase 1 study evaluating the safety and tolerability
of pegaspargase in combination with gemcitabine in advanced metastatic solid
tumors and lymphoma.
AB - PURPOSE: To evaluate the maximum tolerated dose, safety profile,
pharmacokinetics, and pharmacodynamics of pegaspargase (PEG-ASP) in combination
with gemcitabine in patients with advanced metastatic solid tumors and lymphoma.
METHODS: We conducted a multicenter, open label, nonrandomized, Phase 1 dose
escalation study designed to evaluate up to 10 cohorts of patients with advanced
or metastatic solid tumors and lymphoma. Seventeen patients were treated with of
PEG-ASP in combination with gemcitabine. RESULTS: The study was terminated early
because the doses for PEG-ASP suggested for de-escalation were predicted not to
provide desired sustained asparaginase concentrations based on the analysis of
treated patients.
PMID- 25844819
TI - Solution-mediated selective nanosoldering of carbon nanotube junctions for
improved device performance.
AB - As-grown randomly aligned networks of carbon nanotubes (CNTs) invariably suffer
from limited transport properties due to high resistance at the crossed junctions
between CNTs. In this work, Joule heating of the highly resistive CNT junctions
is carried out in the presence of a spin-coated layer of a suitable chemical
precursor. The heating triggers thermal decomposition of the chemical precursor,
tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), and causes local deposition of
Pd nanoparticles at the CNT junctions, thereby improving the on/off current ratio
and mobility of CNT network devices by an average factor of ~6. This process can
be conducted either in air or under vacuum depending on the characteristics of
the precursor species. The solution-mediated nanosoldering process is simple,
fast, scalable with manufacturing techniques, and extendable to the
nanodeposition of a wide variety of materials.
PMID- 25844820
TI - Socio-Demographic Factors, Social Support, Quality of Life, and HIV/AIDS in
Ghana.
AB - The increase in the access to biomedical interventions for people living with
HIV/AIDS in the developing world has not been adequately matched with the
requisite psychosocial treatments to help improve the effectiveness of biomedical
interventions. Therefore, in this study the author seeks to determine whether
socio-demographic characteristics and social support are associated with quality
of life in individuals diagnosed with HIV/AIDS in Ghana. A convenience sample of
300 HIV/AIDS support group members was obtained via cross-sectional design
survey. The Medical Outcome Studies (MOS) HIV Health Survey, the MOS Social
Support Survey (MOS-SSS), and demographic questionnaire instruments were used to
assess quality of life, social support, and demographic information respectively.
Multiple regression analysis showed that there was a positive association between
overall social support and overall quality of life (r = .51). It also showed that
being younger, male, attending support group meetings for over a year, and having
>= 13 years of schooling related to higher quality of life. Implications of the
findings for practice, policy, and research in Ghana and the rest of the
developing world are discussed.
PMID- 25844822
TI - Stage IIIC Endometrial Cancer: Relapse and Survival Outcomes in Women Treated
With Pelvic or Extended Field Para-Aortic Nodal Radiation Therapy.
AB - PURPOSE: The optimal radiation (RT) volume for node-positive endometrial cancer
is controversial. This study evaluates clinical outcomes in patients with stage
IIIC, N1 endometrial cancer who received RT to the pelvis (PV RT) or pelvis plus
para-aortic nodes (PV-PAN RT). METHODS: Overall, there were 89 women with stage
IIIC endometrial cancer. Of these, 57 women had N1-only disease, forming the
study cohort. Clinicopathologic characteristics, recurrence rates, endometrial
cancer-specific survival (ECSS), and overall survival (OS) were examined among
patients treated with pelvic RT (n=23) compared with pelvic plus para-aortic RT
(n=34). Multivariable analysis of ECSS and OS was performed using Cox regression
modeling. RESULTS: Median follow-up was 5.1 years. Adjuvant chemotherapy was used
in 51/57 (89%) of N1 cases. Women with N1 disease who received PV-PAN RT compared
with PV RT experienced lower recurrence (26% vs. 52%, P=0.06) and higher survival
rates (5 y ECSS 81.5% vs. 47.0%, P=0.04 and OS 79.1% vs. 47.0%, P=0.01). On
multivariable analysis, RT volume was not significantly associated with OS,
whereas chemotherapy was associated with improved ECSS and OS. CONCLUSIONS: RT
conferred excellent local control, whereas chemotherapy was associated with
improved survival in women with N1 endometrial cancer. Distant relapse remains
the most common site of recurrence despite chemotherapy.
PMID- 25844823
TI - Eligibility of Metastatic Pancreatic Cancer Patients for First-Line Palliative
Intent nab-Paclitaxel Plus Gemcitabine Versus FOLFIRINOX.
AB - OBJECTIVES: The PRODIGE and MPACT trials showed superiority of FOLFIRINOX and nab
paclitaxel plus gemcitabine (NG) over gemcitabine alone, respectively. However,
both had strict inclusion criteria. We sought to determine the characteristics of
patients with metastatic pancreatic cancer (MPC) which inform the appropriateness
of first-line chemotherapy FOLFIRINOX and NG in routine practice. MATERIALS AND
METHODS: Patients with MPC who initiated palliative chemotherapy with gemcitabine
from 2000 to 2011 at the British Columbia Cancer Agency were identified.
Clinicopathologic variables and outcomes were retrospectively collected and
compared among groups. Eligibility criteria for each regimen were in accordance
with the respective pivotal phase III trials. RESULTS: A total of 473 patients
were included: 25% of the patients were eligible for FOLFIRINOX versus 45% for
NG. Main reasons for FOLFIRINOX ineligibility were Eastern Cooperative Oncology
Group (ECOG) performance status (PS)>=2 (56.5%), age older than 75 years (19.0%),
and bilirubin>1.5* upper limit of normal (18.6%), whereas those for NG
ineligibility were bilirubin > upper limit of normal (24.5%), ECOG PS>=3 (14.6%),
and cardiac dysfunction (13.8%). Univariate analyses revealed that FOLFIRINOX and
NG-eligible patients had longer median overall survival than their respective
ineligible group (8.6 vs. 4.7 mo, P<0.001; 6.7 vs. 4.9 mo, P=0.008,
respectively). After accounting for ECOG PS in the multivariate model, however,
eligibility for either FOLFIRINOX or NG no longer predicted for better overall
survival. CONCLUSIONS: The majority of patients with MPC are not candidates to
either NG or FOLFIRINOX due to restrictive eligibility requirements. Specific
trials addressing the unmet needs of protocol ineligible patients are warranted.
PMID- 25844824
TI - Factors Associated With Guideline-recommended KRAS Testing in Colorectal Cancer
Patients: A Population-based Study.
AB - OBJECTIVES: Response to epidermal growth factor receptor inhibitors is poorer
among stage IV colorectal cancer (CRC) patients with KRAS mutations; thus KRAS
testing is recommended before treatment. KRAS testing was collected by
Surveillance, Epidemiology, and End Results (SEER) registries for 2010 CRC cases,
and our goal was to provide the first population-based estimates of testing in
the United States. METHODS: SEER CRC cases diagnosed in 2010 were evaluated
(n=30,351). chi tests and logistic regression were conducted to determine patient
characteristics associated with KRAS testing, stratified by stages I-III versus
stage IV. Log-rank tests were used to examine survival by testing status.
RESULTS: KRAS testing among stage IV cases ranged from 39% in New Mexico to 15%
in Louisiana. In the model, younger age, being married, living in a metropolitan
area, and having primary site surgery were associated with greater odds of
receiving KRAS testing. Those who received testing had significantly better
survival than those who did not (P<0.0001). Among those who received testing,
there was no significant difference in survival by mutated versus wild-type KRAS.
Five percent of stage I-III cases received testing. CONCLUSIONS: Wide variation
in documented KRAS testing for stage IV CRC patients exists among SEER
registries. Age remained highly significant in multivariate models, suggesting
that it plays an independent role in the patient and/or provider decision to be
tested. Further research is needed to determine drivers of variation in testing,
as well as reasons for testing in stage I-III cases where it is not recommended.
PMID- 25844825
TI - Seven-Year Outcomes Following Accelerated Partial Breast Irradiation Stratified
by ASTRO Consensus Groupings.
AB - OBJECTIVES: Limited long-term data exist regarding outcomes for patients treated
with accelerated partial breast irradiation (APBI), particularly, when stratified
by American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) risk
groups. The purpose of this analysis is to present 5- and 7-year outcomes
following APBI based on CS groupings. MATERIALS AND METHODS: A total of 690
patients with early-stage breast cancer underwent APBI from 1993 to 2012,
receiving interstitial brachytherapy (n=195), balloon-based brachytherapy
(n=290), or 3-dimensional conformal radiotherapy (n=205) at a single institution.
Patients were stratified into suitable, cautionary, and unsuitable groups with 5
year outcomes analyzed. Seven-year outcomes were analyzed for a subset with
follow-up of >=2 years (n=625). RESULTS: Median follow-up was 6.7 years (range,
0.1 to 20.1 y). Patients assigned to cautionary and unsuitable categories were
more likely to have high-grade tumors (21% to 25% vs. 9%, P=0.001), receive
chemotherapy (15% to 38% vs. 6%, P<0.001), and have close/positive margins (9% to
11% vs. 0%, P<0.001). There was no difference in ipsilateral breast tumor
recurrence at 5 or 7 years: 2.2%, 1.2%, 2.8% at 5 years (P=0.57), and 2.2%, 1.9%,
4.6% at 7 years (P=0.58) in the suitable, cautionary, and unsuitable groups,
respectively. As compared with the suitable group, increased rates of distant
metastases were noted for the unsuitable and cautionary groups at 5 years
(P=0.04). CONCLUSIONS: No differences in rates of ipsilateral breast tumor
recurrence were seen at 5 or 7 years when stratified by ASTRO CS groupings.
Modest increases in distant recurrence were noted in the cautionary and
unsuitable groups. These findings suggest that the ASTRO CS groupings stratify
more for systemic recurrence and may not appropriately select patients for whole
versus partial breast irradiation.
PMID- 25844821
TI - Lansoprazole Is Associated with Worsening Asthma Control in Children with the
CYP2C19 Poor Metabolizer Phenotype.
AB - RATIONALE: Gastric acid blockade in children with asymptomatic acid reflux has
not improved asthma control in published studies. There is substantial population
variability regarding metabolism of and response to proton pump inhibitors based
on metabolizer phenotype. How metabolizer phenotype affects asthma responses to
acid blockage is not known. OBJECTIVES: To determine how metabolizer phenotype
based on genetic analysis of CYP2C19 affects asthma control among children
treated with a proton pump inhibitor. METHODS: Asthma control as measured by the
Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month
clinical trial of lansoprazole in children with asthma was analyzed for
associations with surrogates of lansoprazole exposure (based on treatment
assignment and metabolizer phenotype). Groups included placebo-treated children;
lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor
metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes.
Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two
wild-type alleles were extensive metabolizers (EMs). MEASUREMENTS AND MAIN
RESULTS: Asthma control through most of the treatment period was unaffected by
lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed
significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P =
0.02) and placebo-treated children (+0.16 vs. -0.23; P < 0.01). Differences in
asthma control were not associated with changes in gastroesophageal reflux
symptoms. Recent upper respiratory infection worsened asthma control, and this
upper respiratory infection effect may be more pronounced among lansoprazole
treated PMs. CONCLUSIONS: Children with the PM phenotype developed worse asthma
control after 6 months of lansoprazole treatment for poorly controlled asthma.
Increased exposure to proton pump inhibitor may worsen asthma control by altering
responses to respiratory infections. Clinical trial registered with
www.clinicaltrials.gov (NCT00604851).
PMID- 25844826
TI - Mapping of SrTm4, a Recessive Stem Rust Resistance Gene from Diploid Wheat
Effective to Ug99.
AB - Race TTKSK (or Ug99) of Puccinia graminis f. sp. tritici, the causal agent of
wheat stem rust, is a serious threat to wheat production worldwide. Diploid
wheat, Triticum monococcum (genome Am), has been utilized previously for the
introgression of stem rust resistance genes Sr21, Sr22, and Sr35. Multipathotype
seedling tests of biparental populations demonstrated that T. monococcum
accession PI 306540 collected in Romania contains a recessive resistance gene
effective to all P. graminis f. sp. tritici races screened, including race TTKSK.
We will refer to this gene as SrTm4, which is the fourth stem rust resistance
gene characterized from T. monococcum. Using two mapping populations derived from
crosses of PI 272557*PI 306540 and G3116*PI 306540, we mapped SrTm4 on chromosome
arm 2AmL within a 2.1 cM interval flanked by sequence-tagged markers BQ461276 and
DR732348, which corresponds to a 240-kb region in Brachypodium chromosome 5. The
eight microsatellite and nine sequence-tagged markers linked to SrTm4 will
facilitate the introgression and accelerate the deployment of SrTm4-mediated Ug99
resistance in wheat breeding programs.
PMID- 25844827
TI - Resurgence of Pseudoperonospora cubensis: The Causal Agent of Cucurbit Downy
Mildew.
AB - The downy mildew pathogen, Pseudoperonospora cubensis, which infects plant
species in the family Cucurbitaceae, has undergone major changes during the last
decade. Disease severity and epidemics are far more destructive than previously
reported, and new genotypes, races, pathotypes, and mating types of the pathogen
have been discovered in populations from around the globe as a result of the
resurgence of the disease. Consequently, disease control through host plant
resistance and fungicide applications has become more complex. This resurgence of
P. cubensis offers challenges to scientists in many research areas including
pathogen biology, epidemiology and dispersal, population structure and population
genetics, host preference, host-pathogen interactions and gene expression,
genetic host plant resistance, inheritance of host and fungicide resistance, and
chemical disease control. This review serves to summarize the current status of
this major pathogen and to guide future management and research efforts within
this pathosystem.
PMID- 25844828
TI - Resistance Against Basil Downy Mildew in Ocimum Species.
AB - Downy mildew, caused by the oomycete Peronospora belbahrii, is a devastating
disease of sweet basil. In this study, 113 accessions of Ocimum species (83 Plant
Introduction entries and 30 commercial entries) were tested for resistance
against downy mildew at the seedling stage in growth chambers, and during three
seasons, in the field. Most entries belonging to O. basilicum were highly
susceptible whereas most entries belonging to O. americanum, O.
kilimanadascharicum, O. gratissimum, O. campechianum, or O. tenuiflorum were
highly resistant at both the seedling stage and the field. Twenty-seven highly
resistant individual plants were each crossed with the susceptible sweet basil
'Peri', and the F1 progeny plants were examined for disease resistance. The F1
plants of two crosses were highly resistant, F1 plants of 24 crosses were
moderately resistant, and F1 plants of one cross were susceptible, suggesting
full, partial, or no dominance of the resistance gene(s), respectively. These
data confirm the feasibility of producing downy mildew-resistant cultivars of
sweet basil by crossing with wild Ocimum species.
PMID- 25844829
TI - Identifying risky drinking patterns over the course of Saturday evenings: An
event-level study.
AB - Gaining a better understanding of young adults' excessive drinking on nights out
is crucial to ensure prevention efforts are effectively targeted. This study aims
to identify Saturdays with similar evening drinking patterns and corresponding
situation-specific and person-specific determinants. Growth mixture modeling and
multilevel logistic regressions were based on 3,084 questionnaires completed by
164 young adults on 514 evenings via the Internet-based cell phone optimized
assessment technique (ICAT). The results showed that the 2-group solution best
fitted the data with a "stable low" drinking pattern (64.0% of all evenings, 0.2
drinks per hour on average, 1.5 drinks in total) and an "accelerated" drinking
pattern (36.0%, increased drinking pace from about 1 drink per hour before 8 p.m.
to about 2 drinks per hour after 10 p.m.; 11.5 drinks in total). The presence of
more same-sex friends (ORwomen = 1.29, 95% CI [1.09-1.53]; ORmen = 1.35, 95% CI
[1.15-1.58], engaging in predrinking (ORwomen = 2.80, 95% CI [1.35-5.81]; ORmen =
3.78, 95% CI [1.67-8.55] and more time spent in drinking establishments among men
(ORmen = 1.46, 95% CI [1.12-1.90] predicted accelerated drinking evenings.
Accelerated drinking was also likely among women scoring high on coping motives
at baseline (ORwomen = 2.40, 95% CI [1.43-4.03] and among men scoring high on
enhancement motives (ORmen = 2.36, 95% CI [1.46-3.80]. To conclude, with a total
evening consumption that is almost twice the threshold for binge drinking, the
identified accelerated drinking pattern signifies a burden for individual and
public health. Promoting personal goal setting and commitment, and reinforcing
self-efficacy and resistance skills training appear to be promising strategies to
impede the acceleration of drinking pace on Saturday evenings.
PMID- 25844830
TI - Interaction of depressive symptoms and smoking abstinence on delay discounting
rates.
AB - Delay discounting and depressive symptomatology have strong connections with
smoking. However, few studies have examined interactions across delay
discounting, depressive symptoms, and smoking status. The primary goal of this
secondary analysis was to assess the interrelations across these 3 variables
among treatment-seeking smokers. Delay discounting and depressive symptoms were
assessed in 95 smokers enrolled in a clinical trial for smoking cessation at
intake and 6-month follow-up. Participants with and without depressive symptoms
did not differ in their discounting rates neither at intake nor at 6-month follow
up. However, delay discounting was significantly lower among abstainers at 6
month follow-up, and changes in discounting associated with smoking status were
more pronounced among participants with depressive symptoms. These results
clarify the relationship between delay discounting and depressive symptoms among
current and former smokers and suggest that the association between smoking
abstinence and lower delay discounting is significantly greater among individuals
with depressive symptoms versus those who do not have depressive symptomatology.
PMID- 25844832
TI - Older adults who are at risk of driving under the influence: A latent class
analysis.
AB - Despite increasing rates of substance use among older adults, their risk of
driving under the influence of alcohol and/or drugs (DUI) has received scant
research attention. This study identified DUI risk profiles among individuals
aged 50+ years based on their substance use patterns, previous DUI incidents, and
previous arrests. This study's analytic sample of 11,188 individuals came from
the public use data sets of the 2008 to 2012 National Survey on Drug Use and
Health. Latent class analysis identified a 4-class model as the most
parsimonious. Class 1 (63% of the analytic sample; lowest risk group) exhibited
the lowest probabilities of substance use and trouble with law while Class 4 (9%
of the sample; highest risk group) included binge/heavy drinkers who are also
likely to use illicit drugs and had the highest probabilities of self-reported
DUI and previous arrests. Class 2 (18.5%) and Class 3 (9.5%) exhibited low-to
medium DUI risks. Class 4 had the highest proportions of Blacks and divorced or
never married persons and had lowest education and income, poorest self-rated
health, and highest rates of mental health problems of all classes. Screening for
substance abuse and comorbid mental health conditions should be included in
protocols for assessing older adults' driving safety. More effort is also needed
to improve access to substance abuse treatment and address mental health problems
among older adults at high risk for DUI.
PMID- 25844831
TI - The interactive effects of emotion regulation and alcohol intoxication on lab
based intimate partner aggression.
AB - This study draws on Finkel and Eckhardt's (2013) I3 framework to examine the
interactive effects of 2 emotion regulation strategies-anger rumination (an
impellance factor) and reappraisal (an inhibition factor), and alcohol
intoxication (a disinhibition factor)-on intimate partner aggression (IPA)
perpetration as measured with an analogue aggression task. Participants were 69
couples recruited from a large Midwestern university (total N = 138).
Participants' trait rumination and reappraisal were measured by self-report.
Participants were randomized individually to an alcohol or placebo condition,
then recalled an anger event while using 1 of 3 randomly assigned emotion
regulation conditions (rumination, reappraisal, or uninstructed). Following this,
participants completed an analogue aggression task involving ostensibly assigning
white noise blasts to their partner. Participants in the alcohol condition
displayed greater IPA than participants in the placebo condition for provoked
IPA, but not unprovoked IPA. Results also revealed interactions such that for
those in the alcohol and rumination group, higher trait reappraisal was related
to lower unprovoked IPA. For provoked IPA, higher trait rumination was related to
greater IPA among those in the alcohol and rumination condition and those in the
placebo and uninstructed condition. In general, results were consistent with I3
theory, suggesting that alcohol disinhibits, rumination impels, and trait
reappraisal inhibits IPA. The theoretical and clinical implications of these
findings are discussed in the context of current knowledge about the influence of
alcohol intoxication and emotion regulation strategies on IPA perpetration.
PMID- 25844833
TI - Inaugural editorial.
PMID- 25844835
TI - Correction to Frone and Trinidad (2014).
PMID- 25844834
TI - Randomized controlled trial of brief alcohol screening and intervention for
college students for heavy-drinking mandated and volunteer undergraduates: 12
month outcomes.
AB - This is the first randomized trial testing whether heavy-drinking undergraduates
mandated to the Brief Alcohol Screening and Intervention for College Students
(BASICS) program following a campus alcohol violation would benefit as much as
heavy-drinking volunteers up to 1 year postintervention using control groups with
high-risk drinkers to model disciplinary-related and naturalistic changes in
drinking. Participants (61% male; 51% mandated; 84% Caucasian; M age = 20.14
years) were screened for heavy drinking and randomized to BASICS (n = 115) or
assessment-only control (n = 110). Outcome measures (drinking, alcohol problems)
were collected at baseline, 4 weeks, 3, 6, and 12 months postintervention. At 4
weeks postintervention, intent-to-treat multilevel longitudinal models showed
that regardless of referral group (mandated or volunteer), BASICS significantly
decreased weekly drinking, typical drinks, and peak drinks relative to controls
(ds = .41-.92). BASICS had a large effect on decreases in alcohol problems (d =
.87). At 12 months postintervention, BASICS participants (regardless of referral
group) reported significantly fewer alcohol problems (d = .56) compared with
controls. Significant long-term intervention gains for peak and typical drinks
were sustained in both referral groups relative to controls (ds = .42; .11).
Referral group had no significant main effect and did not interact with
intervention condition to predict outcomes. Given that BASICS was associated with
less drinking and fewer alcohol problems (even among heavier drinking mandated
students up to 1 year postintervention), provision of BASICS-style programs
within disciplinary settings may help reduce heavy and problematic drinking among
at-risk students. (PsycINFO Database Record
PMID- 25844836
TI - Immune response following postexposure rabies prophylaxis.
PMID- 25844837
TI - Measuring zebrafish turning rate.
AB - Zebrafish is becoming a popular animal model in preclinical research, and
zebrafish turning rate has been proposed for the analysis of activity in several
domains. The turning rate is often estimated from the trajectory of the fish
centroid that is output by commercial or custom-made target tracking software run
on overhead videos of fish swimming. However, the accuracy of such indirect
methods with respect to the turning rate associated with changes in heading
during zebrafish locomotion is largely untested. Here, we compare two indirect
methods for the turning rate estimation using the centroid velocity or position
data, with full shape tracking for three different video sampling rates. We use
tracking data from the overhead video recorded at 60, 30, and 15 frames per
second of zebrafish swimming in a shallow water tank. Statistical comparisons of
absolute turning rate across methods and sampling rates indicate that, while
indirect methods are indistinguishable from full shape tracking, the video
sampling rate significantly influences the turning rate measurement. The results
of this study can aid in the selection of the video capture frame rate, an
experimental design parameter in zebrafish behavioral experiments where activity
is an important measure.
PMID- 25844838
TI - Transcriptomic Analysis of Sinorhizobium meliloti and Medicago truncatula
Symbiosis Using Nitrogen Fixation-Deficient Nodules.
AB - The bacterium Sinorhizobium meliloti interacts symbiotically with legume plant
hosts such as Medicago truncatula to form nitrogen-fixing root nodules. During
symbiosis, plant and bacterial cells differentiate in a coordinated manner,
resulting in specialized plant cells that contain nitrogen-fixing bacteroids.
Both plant and bacterial genes are required at each developmental stage of
symbiosis. We analyzed gene expression in nodules formed by wild-type bacteria on
six plant mutants with defects in nitrogen fixation. We observed differential
expression of 482 S. meliloti genes with functions in cell envelope homeostasis,
cell division, stress response, energy metabolism, and nitrogen fixation. We
simultaneously analyzed gene expression in M. truncatula and observed
differential regulation of host processes that may trigger bacteroid
differentiation and control bacterial infection. Our analyses of developmentally
arrested plant mutants indicate that plants use distinct means to control
bacterial infection during early and late symbiotic stages.
PMID- 25844839
TI - Effect of Oral Pathway on Charged Particles Deposition in Human Bronchial
Airways.
AB - BACKGROUND: In vitro studies to investigate the effect of charged particle
deposition in the oral pathway of human adults have demonstrated substantial
increases in deposition due to an induced charge effect. In the current study,
charged particle deposition in the oral pathway was incorporated in the
stochastic human airway generation model IDEAL (Inhalation, Deposition, and
Exhalation of Aerosols in the Lung) to quantify their effect on bronchial airways
deposition. METHODS: Calculation of increased oral deposition due to charged
particles was performed by a modified version of IDEAL for oral pathway, whereas
deposition in the bronchial airways was carried out by the already employed
efficiency equation. Deposition calculations were performed for 3, 4.5, and 6 MUm
particles at flow rates of 15 and 30 L/min. RESULTS: The enhancement in
deposition is found to be 40 times higher in oral pathway and 6 times higher in
bronchial airways for 3 MUm size particles carrying 2500 elementary charges. For
particles larger than 3 MUm, deposition by impaction dominates over deposition by
particle charges, and hence higher deposition in oral pathway is observed
primarily due to impaction. As a consequence of this increased oral deposition,
bronchial airways deposition decreases. CONCLUSION: By controlling breathing,
aerosol properties, and electrostatic charge, targeted deposition in the human
airways can be improved. Hence, charged particles can therefore be utilized to
give better control on regional drug delivery in the lungs or to filter out toxic
constituents.
PMID- 25844840
TI - Current Therapeutic Options for Esophageal Motor Disorders as Defined by the
Chicago Classification.
AB - With the development of high-resolution manometry and specific metrics to
characterize esophageal motility, the Chicago Classification has become the gold
standard for the diagnosis of esophageal motor disorders. Major and significant
disorders, that is, never observed in healthy subjects, are achalasia,
esophagogastric junction outflow obstruction, distal esophageal spasm, absent
peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is
relevant to predict the response to endoscopic and surgical therapies as several
studies suggest that, pneumatic dilation is less effective than Heller myotomy,
in type III achalasia. Peroral endoscopic myotomy, initially developed in expert
centers, is a promising technique for the treatment of achalasia. The medical
therapeutic options for distal esophageal spasm and hypercontractile esophagus
are smooth muscle relaxants and pain modulators. Intraesophageal injection of
botulinum toxin might be an interesting option for treatment of these disorders
but further studies are required to determine the optimal injection protocol and
the best candidates based on manometric patterns. The treatment of hypotensive
motility disorders is disappointing and relies mainly on dietary and lifestyle
changes as no effective esophageal prokinetic is currently available.
PMID- 25844841
TI - Low-dose Infliximab for Induction and Maintenance Treatment in Chinese Patients
With Moderate to Severe Active Ulcerative Colitis.
AB - GOAL: To evaluate the efficacy of low-dose (3.5 mg/kg) infliximab for induction
and maintenance treatment in Chinese patients with ulcerative colitis.
BACKGROUND: Treatment with 4 to 5 mg/kg of infliximab also proved to be effective
in treating moderate to severe ulcerative colitis. At present there is no
relevant study on the effectiveness of infliximab doses lower than 4 mg/kg in
patients with ulcerative colitis. STUDY: A prospective, randomized, double-blind,
placebo-controlled, and single-centered study was designed. A total of 123
patients (from 17 provinces of China) with moderate to severe active ulcerative
colitis despite treatment with concurrent drugs received placebo or low-dose (3.5
mg/kg) or standard-dose (5 mg/kg) infliximab intravenously at weeks 0, 2, and 6
and then every 8 weeks through week 22. Patients were followed up for 30 weeks.
RESULTS: Overall, 73% and 78% of patients who received low-dose (3.5 mg/kg) and
standard-dose (5 mg/kg) infliximab, respectively, had clinical responses at week
8, as compared with 37% of patients who received placebo (P<0.01 for both
comparisons with placebo). The number of patients who received low-dose (3.5
mg/kg) or standard-dose (5 mg/kg) infliximab with a clinical response at week 30
(63% and 66%, respectively) was more than the patients who received placebo (27%,
P<0.01 for both comparisons). CONCLUSIONS: Chinese patients with moderate to
severe active ulcerative colitis treated with low-dose (3.5 mg/kg) or standard
dose (5 mg/kg) infliximab at weeks 0, 2, and 6 and every 8 weeks thereafter were
more likely to have a clinical response at weeks 8 and 30 than those who received
placebo.
PMID- 25844842
TI - Anesthesiology: Attracting the Best New Science in the Specialty.
PMID- 25844843
TI - Intraoperative Glycemic Control to Prevent Delirium after Cardiac Surgery:
Steering a Course between Scylla and Charybdis.
PMID- 25844845
TI - Noninvasive monitors of blood pressure in the critically ill: what are acceptable
accuracy and precision?
PMID- 25844846
TI - Anatomical basis of the various spread patterns around the femoral nerve in the
inguinal region.
PMID- 25844847
TI - The interplay of spatial attentional biases and mental codes in VSTM:
Developmentally informed hypotheses.
AB - What cognitive processes influence how well we maintain information in visual
short-term memory (VSTM)? We used a developmentally informed design to delve into
the interplay of top-down spatial biases with the nature of the internal memory
codes, motivated by documented changes for both factors over childhood. Seven
year-olds, 11-year-olds, and adults completed a VSTM task in which they decided
whether a probe item had been present in a preceding memory array. Spatial cues
guided participants' attention to the likely location of the to-be-probed item
during maintenance. We manipulated the memoranda to contain either highly
familiar items or unfamiliar abstract shapes. All participants benefited from
cues during maintenance, although benefits were smaller for 7-year-olds than for
older participants. Critically, attentional benefits interacted with the nature
of the memoranda: Better VSTM maintenance was obtained for cued familiar items.
Furthermore, attentional benefits for familiar items correlated with validated
measures of visual, but not verbal, short-term and working memory span. These
data demonstrate that, in addition to the efficiency with which top-down biases
operate during maintenance, the available mental codes for to-be-remembered items
influence VSTM and differentially so over childhood. Attentional biases during
maintenance seem to operate more efficiently on mental representations that are
more robust and can be retrieved more easily. More important, this interaction
follows a quantitative development. The findings elucidate further the dynamic
interplay between attentional control and VSTM across development.
PMID- 25844848
TI - The interplay between values and aggression in adolescence: a longitudinal study.
AB - Values, or the guiding standards of adolescents' lives, influence which behaviors
are considered more justified than others. The relationship between values and
social behavior has been established across many studies including the
relationship of values and aggression. But only a few studies have examined these
relationships among youth. Moreover, a question that remains open is the
direction of these relationships. The present study examined the concurrent and
longitudinal relations between values and peer nominated aggression in 3 time
points with a 1-year interval (8th grade-10th grade) in a sample of 678 Israeli
adolescents (51.2% girls). Students completed the Portrait Values Questionnaire
(PVQ; Schwartz et al., 2001) and 6 items of peer nominations of aggression. As
hypothesized, I found positive associations between aggression and self
enhancement and openness to change values concurrently. Similarly, I obtained
negative associations between aggression and self-transcendence and conservation
values. Moreover, crossed-lagged models revealed that self-enhancement values
were positively associated with aggression 1 year later. The association between
aggression and future self-enhancement values, however, was not significant.
Finally, I found mutual associations between self-transcendence values and
aggression across time.
PMID- 25844849
TI - Increases in maternal education and low-income children's cognitive and
behavioral outcomes.
AB - Although the strong link between maternal education and children's outcomes is
one of the most well-established findings in developmental psychology (Reardon,
2011; Sirin, 2005), less is known about how young, low-income children are
influenced by their mothers completing additional education. In this research,
longitudinal data from the Head Start Impact Study were used to explore the
associations between increases in maternal education and Head Start eligible
children's cognitive skills and behavioral problems in 1st grade. Propensity
score weighting was used to identify a balanced comparison group of 1,362
children whose mothers did not increase their education between baseline (when
children were aged 3 or 4) and children's kindergarten year, who are similar on
numerous covariates to the 262 children whose mothers did increase their
education. Propensity-score weighted regression analyses indicated that increases
in maternal education were positively associated with children's standardized
cognitive scores, but also with higher teacher-reported externalizing behavioral
problems in 1st grade. The increases in externalizing behavioral problems were
larger for children whose mothers had less than a college degree at baseline.
PMID- 25844850
TI - The developmental trajectory of intramaze and extramaze landmark biases in
spatial navigation: An unexpected journey.
AB - Adults learning to navigate to a hidden goal within an enclosed space have been
found to prefer information provided by the distal cues of an environment, as
opposed to proximal landmarks within the environment. Studies with children,
however, have shown that 5- or 7-year-olds do not display any preference toward
distal or proximal cues during navigation. This suggests that a bias toward
learning about distal cues occurs somewhere between the age of 7 years and
adulthood. We recruited 5- to 11-year-old children and an adult sample to explore
the developmental profile of this putative change. Across a series of 3
experiments, participants were required to navigate to a hidden goal in a virtual
environment, the location of which was signaled by both extramaze and intramaze
landmark cues. During testing, these cues were placed into conflict to assess the
search preferences of participants. Consistent with previously reported findings,
adults were biased toward using extramaze information. However, analysis of the
data from children, which incorporated age as a continuous variable, suggested
that older children in our sample were, in fact, biased toward using the
intramaze landmark in our task. These findings suggest the bias toward using
distal cues in spatial navigation, frequently displayed by adults, may be a
comparatively late developing trait, and one that could supersede an initial
developmental preference for proximal landmarks.
PMID- 25844851
TI - Poverty, physical stature, and cognitive skills: Mechanisms underlying children's
school enrollment in Zambia.
AB - Past research suggests robust positive associations between household
socioeconomic status and children's early cognitive development in Western
countries. Relatively little is known about these relations in low-income country
settings characterized by economic adversity, high prevalence of malnutrition and
infectious disease, and relatively lower school enrollment. The present study
develops and empirically evaluates an adapted model of early childhood
development using a sample of 2,711 Zambian 6-year-olds. Early learning in and
out of the home was found to explain much of the relation between socioeconomic
status and children's cognitive skills, including language, nonverbal reasoning,
and executive function. Child height-for-age (a proxy for overall nutritional
status and health) was also predictive of children's cognitive skills and both
early and on-time school enrollment. Implications for global child development,
intervention, and future work are discussed.
PMID- 25844852
TI - Synthesis, Structure, and Ethanol Gas Sensing Properties of In2O3 Nanorods
Decorated with Bi2O3 Nanoparticles.
AB - Bi2O3-decorated In2O3 nanorods were synthesized using a one-step process, and
their structure, as well as the effects of decoration of In2O3 nanorods with
Bi2O3 on the ethanol gas-sensing properties were examined. The multiple networked
Bi2O3-decorated In2O3 nanorod sensor showed responses of 171-1774% at ethanol
concentrations of 10-200 ppm at 200 degrees C. The responses of the Bi2O3
decorated In2O3 nanorod sensor were stronger than those of the pristine-In2O3
nanorod sensors by 1.5-4.9 times at the corresponding concentrations. The two
sensors exhibited short response times and long recovery times. The optimal Bi
concentration in the Bi2O3-decorated In2O3 nanorod sensor and the optimal
operation temperature of the sensor were 20% and 200 degrees C, respectively.
The Bi2O3-decorated In2O3 nanorod sensor showed selectivity for ethanol gas over
other gases. The origin of the enhanced response, sensing speed, and selectivity
for ethanol gas of the Bi2O3-decorated In2O3 nanorod sensor to ethanol gas is
discussed.
PMID- 25844854
TI - Sport-Specific Training Targeting the Proximal Segments and Throwing Velocity in
Collegiate Throwing Athletes.
AB - CONTEXT: The ability to generate, absorb, and transmit forces through the
proximal segments of the pelvis, spine, and trunk has been proposed to influence
sport performance, yet traditional training techniques targeting the proximal
segments have had limited success improving sport-specific performance.
OBJECTIVE: To investigate the effects of a traditional endurance-training program
and a sport-specific power-training program targeting the muscles that support
the proximal segments and throwing velocity. DESIGN: Randomized controlled
clinical trial. SETTING: University research laboratory and gymnasium. PATIENTS
OR OTHER PARTICIPANTS: A total of 46 (age = 20 +/- 1.3 years, height = 175.7 +/-
8.7 cm) healthy National Collegiate Athletic Association Division III female
softball (n = 17) and male baseball (n = 29) players. INTERVENTION(S): Blocked
stratification for sex and position was used to randomly assign participants to 1
of 2 training groups for 7 weeks: a traditional endurance-training group (ET
group; n = 21) or a power-stability-training group (PS group; n = 25). Mean
Outcome Measure(s) : The change score in peak throwing velocity (km/h) normalized
for body weight (BW; kilograms) and change score in tests that challenge the
muscles of the proximal segments normalized for BW (kilograms). We used 2-tailed
independent-samples t tests to compare differences between the change scores.
RESULTS: The peak throwing velocity (ET group = 0.01 +/- 0.1 km/h/kg of BW, PS
group = 0.08 +/- 0.03 km/h/kg of BW; P < .001) and muscle power outputs for the
chop (ET group = 0.22 +/- 0.91 W/kg of BW, PS group = 1.3 +/- 0.91 W/kg of BW; P
< .001) and lift (ET group = 0.59 +/- 0.67 W/kg of BW, PS group = 1.4 +/- 0.87
W/kg of BW; P < .001) tests were higher at postintervention in the PT than in the
ET group. CONCLUSIONS: An improvement in throwing velocity occurred
simultaneously with measures of muscular endurance and power after a sport
specific training regimen targeting the proximal segments.
PMID- 25844853
TI - Using Accelerometer and Gyroscopic Measures to Quantify Postural Stability.
AB - CONTEXT: Force platforms and 3-dimensional motion-capture systems provide an
accurate method of quantifying postural stability. Substantial cost, space, time
to administer, and need for trained personnel limit widespread use of
biomechanical techniques in the assessment of postural stability in clinical or
field environments. OBJECTIVE: To determine whether accelerometer and gyroscope
data sampled from a consumer electronics device (iPad2) provide sufficient
resolution of center-of-gravity (COG) movements to accurately quantify postural
stability in healthy young people. DESIGN: Controlled laboratory study. SETTING:
Research laboratory in an academic medical center. PATIENTS OR OTHER
PARTICIPANTS: A total of 49 healthy individuals (age = 19.5 +/- 3.1 years, height
= 167.7 +/- 13.2 cm, mass = 68.5 +/- 17.5 kg). INTERVENTION(S): Participants
completed the NeuroCom Sensory Organization Test (SOT) with an iPad2 affixed at
the sacral level. MAIN OUTCOME MEASURE(S): Primary outcomes were equilibrium
scores from both systems and the time series of the angular displacement of the
anteroposterior COG sway during each trial. A Bland-Altman assessment for
agreement was used to compare equilibrium scores produced by the NeuroCom and
iPad2 devices. Limits of agreement was defined as the mean bias (NeuroCom - iPad)
+/- 2 standard deviations. Mean absolute percentage error and median difference
between the NeuroCom and iPad2 measurements were used to evaluate how closely the
real-time COG sway measured by the 2 systems tracked each other. RESULTS: The
limits between the 2 devices ranged from -0.5 degrees to 0.5 degrees in SOT
condition 1 to -2.9 degrees to 1.3 degrees in SOT condition 5. The largest
absolute value of the measurement error within the 95% confidence intervals for
all conditions was 2.9 degrees . The mean absolute percentage error analysis
indicated that the iPad2 tracked NeuroCom COG with an average error ranging from
5.87% to 10.42% of the NeuroCom measurement across SOT conditions. CONCLUSIONS:
The iPad2 hardware provided data of sufficient precision and accuracy to quantify
postural stability. Accuracy, portability, and affordability make using the iPad2
a reasonable approach for assessing postural stability in clinical and field
environments.
PMID- 25844855
TI - Neural Excitability Alterations After Anterior Cruciate Ligament Reconstruction.
AB - CONTEXT: Neuromuscular dysfunction is common after anterior cruciate ligament
reconstruction (ACL-R). However, little is known about quadriceps spinal-reflex
and descending corticomotor excitability after ACL-R. Understanding the effects
of ACL-R on spinal-reflex and corticomotor excitability will help elucidate the
origins of neuromuscular dysfunction. OBJECTIVE: To determine whether spinal
reflex excitability and corticomotor excitability differed between the injured
and uninjured limbs of patients with unilateral ACL-R and between these limbs and
the matched limbs of healthy participants. DESIGN: Case-control study. SETTING:
Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 28 patients with
unilateral ACL-R (9 men, 19 women; age = 21.28 +/- 3.79 years, height = 170.95 +/
10.04 cm, mass = 73.18 +/- 18.02 kg, time after surgery = 48.10 +/- 36.17
months) and 29 participants serving as healthy controls (9 men, 20 women; age =
21.55 +/- 2.70 years, height = 170.59 +/- 8.93 cm, mass = 71.89 +/- 12.70 kg)
volunteered. MAIN OUTCOME MEASURE(S): Active motor thresholds (AMTs) were
collected from the vastus medialis (VM) using transcranial magnetic stimulation.
We evaluated VM spinal reflexes using the Hoffmann reflex normalized to maximal
muscle responses (H : M ratio). Voluntary quadriceps activation was measured with
the superimposed-burst technique and calculated using the central activation
ratio (CAR). We also evaluated whether ACL-R patients with high or low voluntary
activation had different outcomes. RESULTS: The AMT was higher in the injured
than in the uninjured limb in the ACL-R group (t27 = 3.32, P = .003) and in the
matched limb of the control group (t55 = 2.05, P = .04). The H : M ratio was
bilaterally higher in the ACL-R than the control group (F1,55 = 5.17, P = .03).
The quadriceps CAR was bilaterally lower in the ACL-R compared with the control
group (F1,55 = 10.5, P = .002). The ACL-R group with low voluntary activation
(CAR < 0.95) had higher AMT than the control group (P = .02), whereas the ACL-R
group with high voluntary activation (CAR >= 0.95) demonstrated higher H : M
ratios than the control group (P = .05). CONCLUSIONS: The higher VM AMT in the
injured limbs of ACL-R patients suggested that corticomotor deficits were present
after surgery. Higher bilateral H : M ratios in ACL-R patients may be a strategy
to reflexively increase excitability to maintain voluntary activation.
PMID- 25844856
TI - A Refined Prediction Model for Core and Lower Extremity Sprains and Strains Among
Collegiate Football Players.
AB - CONTEXT: Researchers have identified high exposure to game conditions, low back
dysfunction, and poor endurance of the core musculature as strong predictors for
the occurrence of sprains and strains among collegiate football players.
OBJECTIVE: To refine a previously developed injury-prediction model through
analysis of 3 consecutive seasons of data. DESIGN: Cohort study. SETTING:
National Collegiate Athletic Association Division I Football Championship
Subdivision football program. PATIENTS OR OTHER PARTICIPANTS: For 3 consecutive
years, all 152 team members (age = 19.7 +/- 1.5 years, height = 1.84 +/- 0.08 m,
mass = 101.08 +/- 19.28 kg) presented for a mandatory physical examination on the
day before initiation of preseason practice sessions. MAIN OUTCOME MEASURE(S):
Associations between preseason measurements and the subsequent occurrence of a
core or lower extremity sprain or strain were established for 256 player-seasons
of data. We used receiver operating characteristic analysis to identify optimal
cut points for dichotomous categorizations of cases as high risk or low risk.
Both logistic regression and Cox regression analyses were used to identify a
multivariable injury-prediction model with optimal discriminatory power. RESULTS:
Exceptionally good discrimination between injured and uninjured cases was found
for a 3-factor prediction model that included equal to or greater than 1 game as
a starter, Oswestry Disability Index score equal to or greater than 4, and poor
wall-sit-hold performance. The existence of at least 2 of the 3 risk factors
demonstrated 56% sensitivity, 80% specificity, an odds ratio of 5.28 (90%
confidence interval = 3.31, 8.44), and a hazard ratio of 2.97 (90% confidence
interval = 2.14, 4.12). CONCLUSIONS: High exposure to game conditions was the
dominant injury risk factor for collegiate football players, but a surprisingly
mild degree of low back dysfunction and poor core-muscle endurance appeared to be
important modifiable risk factors that should be identified and addressed before
participation.
PMID- 25844857
TI - Short-Wave Diathermy Pretreatment and Inflammatory Myokine Response After High
Intensity Eccentric Exercise.
AB - CONTEXT: Various modalities have been used to pretreat skeletal muscle to
attenuate inflammation. OBJECTIVE: To determine the effects of short-wave
diathermy (SWD) preheating treatment on inflammation and stress markers after
eccentric exercise. DESIGN: Controlled laboratory study. SETTING: University
laboratory setting. PATIENTS OR OTHER PARTICIPANTS: Fifteen male (age = 22 +/-
4.9 years, height = 179.75 +/- 9.56 cm, mass = 82.22 +/- 12.67 kg) college-aged
students. INTERVENTION(S): Seven participants were selected randomly to receive
40 minutes of SWD heat treatment (HT), and 8 participants served as the control
(CON) group and rested without SWD. Both groups completed 7 sets of 10
repetitions of a high-intensity eccentric exercise protocol (EEP) at 120% of the
1-repetition maximum (1-RM) leg extension. MAIN OUTCOME MEASURE(S): We biopsied
muscles on days 1, 3 (24 hours post-EEP), and 4 (48 hours post-EEP) and collected
blood samples on days 1, 2 (4 hours post-EEP), 3, and 4. We determined 1-RM on
day 2 (24 hours post-SWD) and measured 1-RM on days 3 and 4. We analyzed the
muscle samples for interleukin 6 (IL-6), tumor necrosis factor alpha, and heat
shock protein 70 and the blood for serum creatine kinase. RESULTS: We found a
group * time interaction for intramuscular IL-6 levels after SWD (F2,26 = 7.13, P
= .003). The IL-6 decreased in HT (F1,6 = 17.8, P = .006), whereas CON showed no
change (P > .05). We found a group * time interaction for tumor necrosis factor
alpha levels (F2,26 = 3.71, P = .04), which increased in CON (F2,14 = 7.16, P =
.007), but saw no changes for HT (P > .05). No group * time interactions were
noted for 1-RM, heat shock protein 70, or creatine kinase (P > .05). CONCLUSIONS:
The SWD preheating treatment provided a treatment effect for intramuscular
inflammatory myokines induced through high-intensity eccentric exercise but did
not affect other factors associated with intense exercise and inflammation.
PMID- 25844859
TI - Biodegradation of carbofuran in soils within Nzoia River Basin, Kenya.
AB - Carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) has been
used within the Nzoia River Basin (NRB), especially in Bunyala Rice Irrigation
Schemes, in Kenya for the control of pests. In this study, the capacity of native
bacteria to degrade carbofuran in soils from NRB was investigated. A gram
positive, rod-shaped bacteria capable of degrading carbofuran was isolated
through liquid cultures with carbofuran as the only carbon and nitrogen source.
The isolate degraded 98% of 100-MUg mL(-1) carbofuran within 10 days with the
formation of carbofuran phenol as the only detectable metabolite. The degradation
of carbofuran was followed by measuring its residues in liquid cultures using
high performance liquid chromatography (HPLC). Physical and morphological
characteristics as well as molecular characterization confirmed the bacterial
isolate to be a member of Bacillus species. The results indicate that this strain
of Bacillus sp. could be considered as Bacillus cereus or Bacillus thuringiensis
with a bootstrap value of 100% similar to the 16S rRNA gene sequences. The
biodegradation capability of the native strains in this study indicates that they
have great potential for application in bioremediation of carbofuran-contaminated
soil sites.
PMID- 25844858
TI - Add-On Treatment with Liraglutide Improves Glycemic Control in Patients with Type
2 Diabetes on Metformin Therapy.
AB - BACKGROUND: Liraglutide is a glucagon-like peptide-1 receptor analog recently
approved for the treatment of type 2 diabetes mellitus (T2DM). We aimed to assess
the efficacy and safety of liraglutide versus glimepiride, as adjunct treatments
to metformin, in achieving glycemic control in Italian patients with T2DM
uncontrolled by metformin alone. SUBJECTS AND METHODS: One hundred seventy-nine
diabetes patients treated with metformin plus liraglutide (1.8 mg) or glimepiride
(4 mg) were retrospectively assessed at baseline, during, and after 18 months of
continuous therapy. RESULTS: Treatment with liraglutide resulted in mean
decreases in hemoglobin A1c (HbA1c) of -1.4%, when compared with glimepiride (
0.4%) (P < 0.001), and was followed by a significant reduction (P < 0.001) in
fasting plasma glucose. Variations in HbA1c occurred independently from weight
loss, which was significantly reduced (P < 0.001) in liraglutide-treated
patients. The percentage of subjects reaching HbA1c levels below 7% or <= 6.5%
was significantly different between the two treated groups (P < 0.001). Treatment
with liraglutide reduced waist circumference (WC) (P < 0.001) and decreased both
systolic and diastolic blood pressure (BP) (P < 0.001). It is interesting that
the study also showed the impact of female gender in predicting a better glycemic
response to liraglutide (P = 0.028). CONCLUSIONS: Liraglutide was more effective
than glimepiride in reducing HbA1c levels in treated patients with T2DM. This was
evident in both genders, but particularly in women. Furthermore, liraglutide
reduced body weight, WC, and BP, which are critical risk factors for
cardiovascular disease.
PMID- 25844860
TI - Pesticides residues in the Prochilodus costatus (Valenciennes, 1850) fish caught
in the Sao Francisco River, Brazil.
AB - The objective of this study was to determine the levels of pesticides in the fish
Prochilodus costatus caught in Sao Francisco River, one of most important rivers
in Brazil. Thirty-six fish were captured in three different areas, and samples of
the dorsal muscle and pooled viscera were collected for toxicological analysis.
We evaluated the presence of 150 different classes of insecticides, fungicides,
herbicides and acaricides by multiresidue analysis technique using liquid
chromatography-tandem mass spectrometry (LC-MS/MS), with the limit of detection
of 5 ppb. In this study, organophosphorus and carbamate pesticides were detected
at the highest levels in the caught fish. Among the 41 organophosphorus
pesticides surveyed, nine types were detected (chlorpyrifos, diazinon,
dichlorvos, disulfoton, ethion, etrimfos, phosalone, phosmet and pyrazophos) in
the muscle, viscera pool, or both in 22 (61.1%) fish. Sampled tissues of 20
(55.6%) fish exhibited at least one of the eight evaluated carbamate pesticides
and their metabolites: aldicarb, aldicarb sulfoxide, carbaryl, carbofuran,
carbosulfan, furathiocarb, methomyl and propoxur. Fungicides (carbendazim,
benalaxyl, kresoxim-methyl, trifloxystrobin, pyraclostrobin and its metabolite BF
500 pyraclostrobin), herbicides (pyridate and fluasifop p-butyl), acaricide
(propargite) and pyrethroid (flumethrin) were also detected. In conclusion, P.
costatus fish caught in the Sao Francisco River contained residues of 17
different pesticides, in both muscles and the viscera pool, indicating heavy
environmental contamination by pesticides in the study area.
PMID- 25844861
TI - Acute toxicity and ecotoxicological risk assessment of rice pesticides to
Lithobates catesbeianus tadpoles.
AB - The objective of this study was to determine the acute toxicity of some
pesticides used in irrigated rice farming to Lithobates catesbeianus tadpoles.
The LC 50-96h for commercial formulations containing bentazon, penoxsulam,
vegetable oil, permethrin and carbofuran, separately and their mixtures, were
determined at the proportions commonly used in the field. The limits of risk
concentrations of these products for the studied species were also established.
The LC 50-96h for tadpoles was 4,530 mg L(-1) for bentazon; 7.52 mg L(-1) for
penoxsulam + 145.66 mg L(-1) of vegetable oil; 81.57 mg L(-1) for vegetable oil;
0.10 mg L(-1) for permethrin; 29.90 mg L(-1) for carbofuran (active ingredients),
and 38.79 times the dose used in the field for the mixture of these products. The
environmental risk was determined only for permethrin, and care should be taken
when using the vegetable oil.
PMID- 25844863
TI - Resistance and virulence factors of Escherichia coli isolated from chicken.
AB - Chicken meat has become an important part of the human diet and besides
contamination by pathogenic Escherichia coli there is a risk of antibiotic
resistance spreading via the food chain. The purpose of this study was to examine
the prevalence of resistance against eight antibiotics and the presence of 14
virulence factors among 75 Escherichia coli strains isolated from chicken meat in
the Czech Republic after classification into phylogenetic groups by the multiplex
PCR method. More than half of strains belonged to A phylogroup, next frequently
represented was B1 phylogroup, which suggests the commensal strains. The other
strains were classified into phylogroups B2 and D, which had more virulence
factors. Almost half of all E. coli strains were resistant to at least one of
eight-tested antibiotics. A multidrug resistance was observed in 13% of strains.
The most prevalent virulence genes were iucD, iss and tsh. None of genes encoding
toxins was detected. Most of E. coli strains isolated from chicken meat can be
considered as nonpathogenic on the basis of analysis of virulence factors,
antibiotic resistance and phylogroups assignment. It can provide a useful tool
for prediction of a potential risk from food contaminated by E. coli.
PMID- 25844862
TI - Assessment of a potential preventive ability of amygdalin in mycotoxin-induced
ovarian toxicity.
AB - The possible effects of a natural substance amygdalin and its combination with
the mycotoxin deoxynivalenol (DON) on the steroid hormone secretion (progesterone
and 17-beta-estradiol) by porcine ovarian granulosa cells (GCs) were examined in
this in vitro study. Ovarian GCs were incubated without (control group) and with
amygdalin (1, 10, 100, 1,000 and 10,000 MUg mL(1)), or its combination with DON
(1 MUg mL(1)) for 24 h. The release of steroid hormones was determined by ELISA.
The progesterone secretion by porcine ovarian GCs was not affected by amygdalin
in comparison to the control. However, the highest amygdalin dose (10,000 MUg
mL(1)) caused a significant stimulation of the 17-beta-estradiol release. A
combination of amygdalin with DON significantly (P < 0.05) increased the
progesterone release at all concentrations. Similarly, a stimulatory effect of
amygdalin co-administered with DON was detected with respect to the 17-beta
estradiol secretion at the highest dose (10,000 MUg mL(1)) of amygdalin and 1 MUg
mL(1) of DON. Noticeable differences between the effects of amygdalin alone and
its combination with DON on the progesterone release were detected. In contrast,
no differences between the stimulatory effects of amygdalin and its combination
with DON on the 17-beta-estradiol synthesis by porcine GCs were observed.
Findings from this in vitro study did not confirm the expected protective effect
of amygdalin on mycotoxin induced reprotoxicity. Our results indicate that the
stimulatory effect of amygdalin combined with DON on the progesterone release was
clearly caused by the DON addition, not by the presence amygdalin per se. On the
other hand, the stimulation of 17-beta-estradiol production was solely caused by
the presence of amygdalin addition. These findings suggest a possible involvement
of both natural substances into the processes of steroidogenesis and appear to be
endocrine modulators of porcine ovaries.
PMID- 25844864
TI - Specificity of Salmonella Typhimurium strain (ATCC 14028) growth responses to
Salmonella serovar-generated spent media.
AB - Salmonella enterica is one of the most prevalent pathogens responsible for
foodborne illness worldwide. Numerous Salmonella serovars have been associated
with the consumption of a variety of products, and limiting food-borne illness
due to Salmonella serovars is a continuing problem for food producers and public
health. The emergence and prevalence of Salmonella serovars has been studied but
the predominant serovars have varied somewhat over the years. The aims of this
research were to compare the aerobic growth responses of selected predominant
foodborne Salmonella serovars, and evaluate how the spent media from different
serovars affects the growth of a well-characterized Salmonella Typhimurium
strain. Growth responses were similar for most strains in spent media except for
S. Typhimurium (ATCC 14028), which exhibited a decrease in growth in the presence
of Salmonella Heidelberg (ARI-14) spent media. This research will provide a
better understanding of the growth differences among several Salmonella serovars
in nutrient limited spent media.
PMID- 25844865
TI - Assessment of a composting process for the treatment of beef cattle manure.
AB - The intensive breeding of beef cattle in Juncosa de les Garrigues (Catalonia,
Spain) leads to the production of a large volume of manure that needs appropriate
management. Land application in the area at agronomic rates is not enough to
ensure good management practices, making necessary extended on-farm storage and
the export of part of the production to long distances. In this context, the
implementation of a collective treatment based on composting could help in
enhancing the handling of manure. We assessed a full-scale composting process
based on turned windrows (W), and involving treatment of beef cattle manure (CM)
alone (two typologies were considered according to carbon-to-nitrogen ratios of
~25 (CM1, W1) and ~14 (CM2, W2)), or mixed with bulking agent (CM2/BA, W3) and
dewatered digested sewage sludge (CM2/BA/DDSS, W4). Composting significantly
improved the transportability of nutrients (final volumes were 40-54% of the
initial volume). Temperature >55 degrees C was reached in all the treatments but
following different time patterns. Under the applied conditions of turning and
rewetting, 14 weeks of processing did not ensure the production of stable, and
mature, compost. Thus, only compost from W1 attained the maximum degree of
stability as well as concentration of ammonium-N < 0.01% (with ammonium-N/nitrate
N ratio of 0.2) and low phytotoxicity. However, high pH, salinity, and heavy
metal contents (Cu and Zn) may limit its final use. Addition of BA was advised to
be kept to minimum, whereas use of DDSS as a co-substrate was not recommended in
agreement to the higher loss of N and levels of heavy metals in the final
compost.
PMID- 25844866
TI - Elemental distribution and uptake by watercress (Nasturtium aquaticum) as a
function of water quality.
AB - Watercress (Nasturtium aquaticum), is an edible plant commonly found in Southern
Africa, which grows both in terrestrial and aquatic environments. The elemental
concentrations in the plant and surrounding water (growth solution) were
investigated to determine the plants nutritional value and to establish impact of
water quality on elemental uptake by the plant. The concentrations in the leaves,
roots and water were analyzed at eight different sites along the east coast of
KwaZulu-Natal, South Africa (30.0000 degrees S, 25.0000 degrees E). Elemental
concentrations in the leaves/roots (MUg g(-1), dry mass) and water
exchangeable/total (MUg L(-1)) at Verulam (situated in the northern part of
KwaZulu-Natal) were: As (1.2/7.5 and 0.053/0.09), Ca (18272/26091 and
0.336/7.15), Cd (0.9/0.8 and 0.004/0.01), Co (37.2/34 and 0/0), Cr (7/35 and
0.003/0.03), Cu (3/19 and 0.016/0.16), Fe (528/4308 and 0.375/0.6), Mg (3444/1141
and 6.4/7), Mn (110/667 and 0/0), Ni (20/63 and 0/0.01), Pb (16/17 and
0.01/0.02), Se (28/11 and 0.003/0.01) and Zn (102/116 and 0.099/0.36). Elemental
uptake was controlled by the plant but water quality did have an impact on
uptake. Concentrations of metals in the leaves were in decreasing order of Ca >
Mg > Fe > Mn > Zn > Cu > Cr > Ni > Pb > Se > Cd > As > Co. The watercress plant
was found to be a rich source of essential elements especially Fe and Cr and
contained low concentrations of the toxic metals investigated thereby making it
safe for human consumption.
PMID- 25844868
TI - Acute Physiological and Mechanical Responses During Resistance Exercise at the
Lactate Threshold Intensity.
AB - The purpose of this study was to examine acute metabolic, mechanical, and cardiac
responses to half-squat (HS) resistance exercise performed at a workload
corresponding to the lactate threshold (LT). Thirteen healthy subjects completed
3 HS exercise tests separated by 48-hour rest periods: a maximal strength or 1
repetition maximum (1RM) test, an incremental load test to establish the % 1RM at
which the LT was reached, and a constant load test at the LT intensity. During
the last test, metabolic, mechanical, and cardiac responses were monitored
respectively through blood lactate concentrations, height (H), average power (AP)
and peak power (PP) recorded in a countermovement jump test, and heart rate (HR).
During the constant load test, lactate concentrations and HR remained stable
whereas significant reductions were detected in H, AP, and PP (p <= 0.05). Only
low correlation was observed between lactate concentrations and the H (r =
0.028), AP (r = 0.072), and PP (r = 0.359) losses produced. Half-squat exercise
at the LT elicits stable HR and blood lactate responses within a predominantly
aerobic metabolism, although this exercise modality induces significant
mechanical fatigue.
PMID- 25844867
TI - Heart Rate-Based Prediction of Fixed Blood Lactate Thresholds in Professional
Team-Sport Players.
AB - The aim of this study was to investigate whether the speed associated with 90% of
maximal heart rate (S90%HRmax) could predict speeds at fixed blood lactate
concentrations of 3 mmol.L(-1) (S3mM) and 4 mmol.L(-1) (S4mM). Professional team
sport players of futsal (n = 10), handball (n = 16), and basketball (n = 10)
performed a 4-stage discontinuous progressive running test followed, if
exhaustion was not previously achieved, by an additional maximal continuous
incremental running test to attain maximal heart rate (HRmax). The individual
S3mM, S4mM, and S90%HRmax were determined by linear interpolation. S3mM (11.6 +/-
1.5 km.h(-1)) and S4mM (12.5 +/- 1.4 km.h(-1)) did not differ (p > 0.05) from
S90%HRmax (12.0 +/- 1.2 km.h(-1)). Very large significant (p < 0.001)
relationships were found between S90%HRmax and S3mM (r = 0.82; standard error of
the estimates [SEE] = 0.87 km.h(-1)), as well as between S90%HRmax and S4mM (r =
0.82; SEE = 0.87 km.h(-1)). S3mM and S4mM inversely correlated with %HRmax
associated with running speeds of 10 and 12 km.h(-1) (r = 0.78-0.81; p < 0.001;
SEE = 0.94-0.87 km.h(-1)). In conclusion, S3mM and S4mM can be accurately
predicted by S90%HRmax in professional team-sport players.
PMID- 25844869
TI - Effects of an Unstable Load on Force and Muscle Activation During a Parallel Back
Squat.
AB - Stability training has become commonplace in the strength and conditioning field.
Although unstable surface training has been investigated, little is known
regarding the efficacy of performing resistance exercises with an unstable load.
The purpose of this study was to determine if performing a parallel back squat
with an unstable load (weights suspended from the bar by an elastic band)
produces greater ground reaction forces (GRFs) and muscle activation in the trunk
and lower extremities than a stable condition (a normally loaded barbell).
Fifteen resistance-trained males (age: 24.2 +/- 3.4 years, mass: 83.4 +/- 18.7
kg) completed 10 repetitions of the back squat, with 60% of their 1 repetition
maximum in both stable and unstable conditions. Peak vertical GRF and the
integrated muscle activity of the rectus femoris, vastus lateralis, vastus
medialis, biceps femoris, soleus, rectus abdominis, external oblique, and erector
spinae muscles on the right side of the body were determined The unstable load
resulted in a small (3.9%) but significant decrease in peak vertical GRF. The
unstable load also produced greater muscle activation in the rectus abdominis,
external oblique, and soleus. The findings of this study suggest that squatting
with an unstable load will increase activation of the stabilizing musculature;
and while force decrements were statistically significant, the decrease was so
small it may not be relevant to practitioners.
PMID- 25844870
TI - High-intensity light-emitting diode vs fluorescent tubes for intensive
phototherapy in neonates.
AB - BACKGROUND: Special blue fluorescent tubes are recommended by the American
Academy of Pediatrics (AAP) as the most effective light source for lowering serum
bilirubin. A high-intensity light-emitting diode ('super LED') could render
intensive phototherapy more effective than the above conventional methods. This
study compared the efficacy and safety of a high-intensity light-emitting diode
bed vs conventional intensive phototherapy with triple fluorescent tube units as
a rescue treatment for severe unconjugated neonatal hyperbilirubinaemia. METHOD:
This was a randomised, prospective trial. Two hundred jaundiced neonates >= 35
weeks gestation who met the criteria for intensive phototherapy as per AAP
guidelines were randomly assigned to be treated either with triple fluorescent
tube units (group 1, n = 100) or a super LED bed (group 2, n = 100). The outcome
was the avoidance of exchange transfusion by successful control of
hyperbilirubinaemia. RESULTS: Statistically significant higher success rates of
intensive phototherapy were achieved among neonates treated with super LED (group
2) than in those treated conventionally (group 1) (87% vs 64%, P = 0.003).
Significantly higher 'bilirubin decline' rates were reported in both haemolytic
and non-haemolytic subgroups treated with the super LED bed compared with a
similar sub-population in the conventionally treated group. Comparable numbers of
neonates in both groups developed rebound jaundice (8% vs 10% of groups 1 and 2,
respectively). Side-effects were mild in both groups, but higher rates of
hyperthermia (12% vs 0%, P = 0.03), dehydration (8% vs 2%, P = 0.26) and skin
rash (39% vs 1%, P = 0.002) were reported in the fluorescent tubes-treated group
compared with the LED group. CONCLUSIONS: Super LED is a safe rescue treatment
for severe neonatal hyperbilirubinaemia, and its implementation may reduce the
need for exchange transfusion.
PMID- 25844871
TI - Alpha-synuclein levels in blood plasma decline with healthy aging.
AB - There is unequivocal evidence that alpha-synuclein plays a pivotal
pathophysiological role in neurodegenerative diseases, and in particular in
synucleinopathies. These disorders present with a variable extent of cognitive
impairment and alpha-synuclein is being explored as a biomarker in CSF, blood
serum and plasma. Considering key events of aging that include proteostasis,
alpha-synuclein may not only be useful as a marker for differential diagnosis but
also for aging per se. To explore this hypothesis, we developed a highly specific
ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels
correlated strongly with age, revealing much lower concentrations in older (avg.
58.1 years) compared to younger (avg. 27.6 years) individuals. This difference
between the age groups was enhanced after acidification of the plasmas
(p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes
or chaperone activity in older individuals. Our results support the concept that
alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance
of the proteostasis network, a key component of healthy aging. Thus, alpha
synuclein may be a novel biomarker of aging, a factor that should be considered
when analyzing its presence in biological specimens.
PMID- 25844872
TI - Correction: the suppression of WRKY44 by GIGANTEA-miR172 pathway is involved in
drought response of Arabidopsis thaliana.
PMID- 25844874
TI - A complementary processes account of the development of childhood amnesia and a
personal past.
AB - Personal-episodic or autobiographical memories are an important source of
evidence for continuity of self over time. Numerous studies conducted with adults
have revealed a relative paucity of personal-episodic or autobiographical
memories of events from the first 3 to 4 years of life, with a seemingly gradual
increase in the number of memories until approximately age 7 years, after which
an adult distribution has been assumed. Historically, this so-called infantile
amnesia or childhood amnesia has been attributed either to late development of
personal-episodic or autobiographical memory (implying its absence in the early
years of life) or to an emotional, cognitive, or linguistic event that renders
early autobiographical memories inaccessible to later recollection. However,
neither type of explanation alone can fully account for the shape of the
distribution of autobiographical memories early in life. In contrast, the
complementary processes account developed in this article acknowledges early,
gradual development of the ability to form, retain, and later retrieve memories
of personally relevant past events, as well as an accelerated rate of forgetting
in childhood relative to adulthood. The adult distribution of memories is
achieved as (a) the quality of memory traces increases, through addition of more,
better elaborated, and more tightly integrated personal-episodic or
autobiographical features; and (b) the vulnerability of mnemonic traces
decreases, as a result of more efficient and effective neural, cognitive, and
specifically mnemonic processes, thus slowing the rate of forgetting. The
perspective brings order to an array of findings from the adult and developmental
literatures.
PMID- 25844875
TI - Informing cognitive abstractions through neuroimaging: the neural drift diffusion
model.
AB - Trial-to-trial fluctuations in an observer's state of mind have a direct
influence on their behavior. However, characterizing an observer's state of mind
is difficult to do with behavioral data alone, particularly on a single-trial
basis. In this article, we extend a recently developed hierarchical Bayesian
framework for integrating neurophysiological information into cognitive models.
In so doing, we develop a novel extension of the well-studied drift diffusion
model (DDM) that uses single-trial brain activity patterns to inform the
behavioral model parameters. We first show through simulation how the model
outperforms the traditional DDM in a prediction task with sparse data. We then
fit the model to experimental data consisting of a speed-accuracy manipulation on
a random dot motion task. We use our cognitive modeling approach to show how
prestimulus brain activity can be used to simultaneously predict response
accuracy and response time. We use our model to provide an explanation for how
activity in a brain region affects the dynamics of the underlying decision
process through mechanisms assumed by the model. Finally, we show that our model
performs better than the traditional DDM through a cross-validation test. By
combining accuracy, response time, and the blood oxygen level-dependent response
into a unified model, the link between cognitive abstraction and neuroimaging can
be better understood.
PMID- 25844876
TI - Expanding the scope of memory search: Modeling intralist and interlist effects in
free recall.
AB - The human memory system is remarkable in its capacity to focus its search on
items learned in a given context. This capacity can be so precise that many
leading models of human memory assume that only those items learned in the
context of a recently studied list compete for recall. We sought to extend the
explanatory scope of these models to include not only intralist phenomena, such
as primacy and recency effects, but also interlist phenomena such as proactive
and retroactive interference. Building on retrieved temporal context models of
memory search (e.g., Polyn, Norman, & Kahana, 2009), we present a substantially
revised theory in which memory accumulates across multiple experimental lists,
and temporal context is used both to focus retrieval on a target list, and to
censor retrieved information when its match to the current context indicates that
it was learned in a nontarget list. We show how the resulting model can
simultaneously account for a wide range of intralist and interlist phenomena,
including the pattern of prior-list intrusions observed in free recall, build-up
of and release from proactive interference, and the ability to selectively target
retrieval of items on specific prior lists (Jang & Huber, 2008; Shiffrin, 1970).
In a new experiment, we verify that subjects' error monitoring processes are
consistent with those predicted by the model.
PMID- 25844873
TI - Robust speech perception: recognize the familiar, generalize to the similar, and
adapt to the novel.
AB - Successful speech perception requires that listeners map the acoustic signal to
linguistic categories. These mappings are not only probabilistic, but change
depending on the situation. For example, one talker's /p/ might be physically
indistinguishable from another talker's /b/ (cf. lack of invariance). We
characterize the computational problem posed by such a subjectively nonstationary
world and propose that the speech perception system overcomes this challenge by
(a) recognizing previously encountered situations, (b) generalizing to other
situations based on previous similar experience, and (c) adapting to novel
situations. We formalize this proposal in the ideal adapter framework: (a) to (c)
can be understood as inference under uncertainty about the appropriate generative
model for the current talker, thereby facilitating robust speech perception
despite the lack of invariance. We focus on 2 critical aspects of the ideal
adapter. First, in situations that clearly deviate from previous experience,
listeners need to adapt. We develop a distributional (belief-updating) learning
model of incremental adaptation. The model provides a good fit against known and
novel phonetic adaptation data, including perceptual recalibration and selective
adaptation. Second, robust speech recognition requires that listeners learn to
represent the structured component of cross-situation variability in the speech
signal. We discuss how these 2 aspects of the ideal adapter provide a unifying
explanation for adaptation, talker-specificity, and generalization across talkers
and groups of talkers (e.g., accents and dialects). The ideal adapter provides a
guiding framework for future investigations into speech perception and
adaptation, and more broadly language comprehension.
PMID- 25844877
TI - Risk attitudes in a changing environment: An evolutionary model of the fourfold
pattern of risk preferences.
AB - A striking feature of human decision making is the fourfold pattern of risk
attitudes, involving risk-averse behavior in situations of unlikely losses and
likely gains, but risk-seeking behavior in response to likely losses and unlikely
gains. Current theories to explain this pattern assume particular psychological
processes to reproduce empirical observations, but do not address whether it is
adaptive for the decision maker to respond to risk in this way. Here, drawing on
insights from behavioral ecology, we build an evolutionary model of risk
sensitive behavior, to investigate whether particular types of environmental
conditions could favor a fourfold pattern of risk attitudes. We consider an
individual foraging in a changing environment, where energy is needed to prevent
starvation and build up reserves for reproduction. The outcome, in terms of
reproductive value (a rigorous measure of evolutionary success), of a one-off
choice between a risky and a safe gain, or between a risky and a safe loss,
determines the risk-sensitive behavior we should expect to see in this
environment. Our results show that the fourfold pattern of risk attitudes may be
adaptive in an environment in which conditions vary stochastically but are
autocorrelated in time. In such an environment the current options provide
information about the likely environmental conditions in the future, which affect
the optimal pattern of risk sensitivity. Our model predicts that risk preferences
should be both path dependent and affected by the decision maker's current state.
PMID- 25844878
TI - Slow down and remember to remember! A delay theory of prospective memory costs.
AB - Event-based prospective memory (PM) requires a deferred action to be performed
when a target event is encountered in the future. Individuals are often slower to
perform a concurrent ongoing task when they have PM task requirements relative to
performing the ongoing task in isolation. Theories differ in their detailed
interpretations of this PM cost, but all assume that the PM task shares limited
capacity resources with the ongoing task. In what was interpreted as support of
this core assumption, diffusion model fits reported by Boywitt and Rummel (2012)
and Horn, Bayen, and Smith (2011) indicated that PM demands reduced the rate of
accumulation of evidence about ongoing task choices. We revaluate this support by
fitting both the diffusion and linear ballistic accumulator (Brown & Heathcote,
2008) models to these same data sets and 2 new data sets better suited to model
fitting. There was little effect of PM demands on evidence accumulation rates,
but PM demands consistently increased the evidence required for ongoing task
response selection (response thresholds). A further analysis of data reported by
Lourenco, White, and Maylor (2013) found that participants differentially
adjusted their response thresholds to slow responses associated with stimuli
potentially containing PM targets. These findings are consistent with a delay
theory account of costs, which contends that individuals slow ongoing task
responses to allow more time for PM response selection to occur. Our results call
for a fundamental reevaluation of current capacity-sharing theories of PM cost
that until now have dominated the PM literature.
PMID- 25844879
TI - Concerns about the Australian Institute of Health and Welfare's information on
capital investment for healthcare.
PMID- 25844880
TI - Two-photon fluorescent probes for biological Mg(2+) detection based on 7
substituted coumarin.
AB - Two novel water-soluble coumarin-based compounds (OC7, NC7) were designed and
synthesized as two-photon fluorescent probes for biological Mg(2+) detection. The
compounds feature a beta-keto acid as a high selective binding site for Mg(2+)
and the coumarin framework as the two-photon fluorophore. OC7 and NC7 show
significant "off-on" detecting signals (9.05-fold and 23.8-fold fluorescence
enhancement) and lower detection limits compared with previous reported two
photon fluorescent probes for Mg(2+). Moreover, OC7-Mg(2+) and NC7-Mg(2+) exhibit
large two-photon absorption cross sections (340 and 615 GM) at the near-infrared
wavelengths (740 and 860 nm), which indicates that the probes are very suitable
for detection of Mg(2+) in vivo. Both OC7 and NC7 are pH-insensitive and of low
cytotoxicity and can be applied to image intracellular Mg(2+) under two-photon
microscopy (TPM). Our results provide a strategy to modify the coumarin
fluorophore to get better two-photon fluorescent properties. And the results also
suggest that electronic density of beta-keto acid plays a very important role in
the recognition of Mg(2+).
PMID- 25844881
TI - A patient with a biventricular pacemaker presenting with chest pain.
PMID- 25844882
TI - Effect of Moderate to Vigorous Physical Activity on All-Cause Mortality in Middle
aged and Older Australians.
AB - IMPORTANCE: Few studies have examined how different proportions of moderate and
vigorous physical activity affect health outcomes. OBJECTIVE: To examine whether
the proportion of total moderate to vigorous activity (MVPA) that is achieved
through vigorous activity is associated with all-cause mortality independently of
the total amount of MVPA. DESIGN, SETTING, AND PARTICIPANTS: We performed a
prospective cohort study with activity data linked to all-cause mortality data
from February 1, 2006, through June 15, 2014, in 204,542 adults aged 45 through
75 years from the 45 and Up population-based cohort study from New South Wales,
Australia (mean [SD] follow-up, 6.52 [1.23] years). Associations between
different contributions of vigorous activity to total MVPA and mortality were
examined using Cox proportional hazards models, adjusted for total MVPA and
sociodemographic and health covariates. EXPOSURES: Different proportions of total
MVPA as vigorous activity. Physical activity was measured with the Active
Australia Survey. MAIN OUTCOMES AND MEASURES: All-cause mortality during the
follow-up period. RESULTS: During 1,444,927 person-years of follow-up, 7435
deaths were registered. Compared with those who reported no MVPA (crude death
rate, 8.34%), the adjusted hazard ratios for all-cause mortality were 0.66 (95%
CI, 0.61-0.71; crude death rate, 4.81%), 0.53 (95% CI, 0.48-0.57; crude death
rate, 3.17%), and 0.46 (95% CI, 0.43-0.49; crude death rate, 2.64%) for reporting
10 through 149, 150 through 299, and 300 min/wk or more of activity,
respectively. Among those who reported any MVPA, the proportion of vigorous
activity revealed an inverse dose-response relationship with all-cause mortality:
compared with those reporting no vigorous activity (crude death rate, 3.84%) the
fully adjusted hazard ratio was 0.91 (95% CI, 0.84-0.98; crude death rate, 2.35%)
in those who reported some vigorous activity (but <30% of total activity) and
0.87 (95% CI, 0.81-0.93; crude death rate, 2.08%) among those who reported 30% or
more of activity as vigorous. These associations were consistent in men and
women, across categories of body mass index and volume of MVPA, and in those with
and without existing cardiovascular disease or diabetes mellitus. CONCLUSIONS AND
RELEVANCE: Among people reporting any activity, there was an inverse dose
response relationship between proportion of vigorous activity and mortality. Our
findings suggest that vigorous activities should be endorsed in clinical and
public health activity guidelines to maximize the population benefits of physical
activity.
PMID- 25844883
TI - The Human Alzheimer Disease Project: A New Call to Arms.
PMID- 25844884
TI - Moving to high-value care: more thoughtful use of cardiopulmonary resuscitation.
PMID- 25844886
TI - Using physical activity to gain the most public health bang for the buck.
PMID- 25844887
TI - Temperature sensitivity of nanochannel electrical conductance.
AB - Electrical measurement is a widely used technique for the characterization of
nanofluidic devices. The electrical conductivity of electrolytes is known to be
dependent on temperature. However, the similarity of the temperature sensitivity
of the electrical conductivity for bulk and nanochannels has not been validated.
In this work, we present the results from experimental measurements as well as
analytical modeling that show the significant difference between bulk and
nanoscale. The temperature sensitivity of the electrical conductance of
nanochannel is higher at low ionic concentration where the nanofluidic transport
is governed by the electrostatic effects from the wall. Neglecting this effect
can result in significant errors for high temperature measurements. Additionally,
the temperature sensitivity of the nanochannel conductance allows to measure the
enthalpy change of surface reactions at low ionic concentrations.
PMID- 25844888
TI - Electroconvulsive therapy for obsessive-compulsive disorder: a systematic review.
AB - OBJECTIVE: Surgical therapies for treatment-refractory obsessive-compulsive
disorder (OCD), such as deep brain stimulation or psychosurgery, remain
unattainable for many patients. Despite the long-held view that electroconvulsive
therapy (ECT) is an ineffective treatment for OCD, there is no systematic review
to support or refute this claim, which is the basis of the current review. DATA
SOURCES: A systematic search of MEDLINE, Web of Science, Scopus, and LILACS
databases was conducted on December 22, 2013, using the terms obsessive
compulsive disorder and electroconvulsive therapy. Reference lists, specific
journals, and clinical trial registries were also scrutinized. No date or
language limitation was imposed on the search. STUDY SELECTION: After irrelevant
and redundant records from the 500 identified titles were excluded, the 50
articles reporting the acute treatment effects of ECT in OCD and related
constructs (involving a total of 279 patients) were analyzed for this study. DATA
EXTRACTION: The relevant sociodemographic, clinical, and outcome data of
individual cases were extracted. Data from individual cases were used to compare
the characteristics of responders versus nonresponders to ECT. RESULTS: Most
selected records were case reports/series; there were no randomized controlled
trials. A positive response was reported in 60.4% of the 265 cases in which
individual responses to ECT were available. ECT responders exhibited a
significantly later onset of OCD symptoms (P = .003), were more frequently
nondepressed (P = .009), more commonly reported being treated with ECT for severe
OCD (P = .01), and received a fewer number of ECT sessions (P = .03). ECT
responders were also less frequently previously treated with adequate trials of
serotonin reuptake inhibitors (P = .05) and cognitive-behavioral therapy (P =
.005). CONCLUSIONS: Although 60% of the reported cases reviewed exhibited some
form of a positive response to ECT, it cannot be stated that this provides
evidence that ECT is indeed effective for OCD.
PMID- 25844889
TI - Interaction Studies of Resolvin E1 Analog (RX-10045) with Efflux Transporters.
AB - PURPOSE: Screening interactions of a resolvin E1 analog (RX-10045) with efflux
transporters (P-glycoprotein [P-gp], multidrug resistance-associated protein
[MRP2], and breast cancer-resistant protein [BCRP]). METHODS: Madin-Darby canine
kidney cells transfected with P-gp, MRP2, and BCRP genes were selected for this
study. [3H]-Digoxin, [3H]-vinblastine and [3H]-abacavir were selected as model
substrates for P-gp, MRP2, and BCRP. Uptake and permeability studies across cell
monolayer in both apical to basal (AP-BL) and BL-AP of these substrates were
conducted in the presence of specific efflux pump inhibitors and RX-10045. Cell
viability studies were conducted with increasing concentrations of RX-10045.
RESULTS: Uptake studies showed a higher accumulation in the presence of
inhibitors (GF120918 and ketoconazole for P-gp; MK571 for MRP2; and beta
estradiol for BCRP) as well as RX-10045. Similarly, dose-dependent inhibition
studies demonstrated higher accumulation of various substrates ([3H]-digoxin,
[3H]-vinblastine, and [3H]-abacavir) in the presence of RX-10045. IC50 values of
dose-dependent inhibition of RX-10045 for P-gp, MRP2, and BCRP were 239+/-11.2,
291+/-79.2, and 300+/-42 MUM, respectively. Cell viability assay indicated no
apparent toxicity up to 350 MUM concentration. Enhanced permeability for model
substrates was observed in the presence of RX-10045. Uptake studies in human
corneal epithelial cells suggest that RX-10045 is a strong inhibitor of organic
cation transporter-1 (OCT-1). CONCLUSIONS: In summary, the resolvin analog (RX
10045) was identified as a substrate/inhibitor for efflux transporters (MRP2 and
BCRP). Also, RX-10045 appears to be a strong inhibitor/substrate of OCT-1. Novel
formulation strategies such as nanoparticles, nanomicelles, and liposomes for
circumventing efflux barriers and delivering higher drug concentrations leading
to a higher therapeutic efficacy may be employed.
PMID- 25844890
TI - Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a
new mechanism.
AB - In type-2 diabetes (T2D), islet amyloid polypeptide (IAPP) self-associates into
toxic assemblies causing islet beta-cell death. Therefore, preventing IAPP
toxicity is a promising therapeutic strategy for T2D. The molecular tweezer CLR01
is a supramolecular tool for selective complexation of K residues in
(poly)peptides. Surprisingly, it inhibits IAPP aggregation at substoichiometric
concentrations even though IAPP has only one K residue at position 1, whereas
efficient inhibition of IAPP toxicity requires excess CLR01. The basis for this
peculiar behavior is not clear. Here, a combination of biochemical, biophysical,
spectroscopic, and computational methods reveals a detailed mechanistic picture
of the unique dual inhibition mechanism for CLR01. At low concentrations, CLR01
binds to K1, presumably nucleating nonamyloidogenic, yet toxic, structures,
whereas excess CLR01 binds also to R11, leading to nontoxic structures.
Encouragingly, the CLR01 concentrations needed for inhibition of IAPP toxicity
are safe in vivo, supporting its development toward disease-modifying therapy for
T2D.
PMID- 25844891
TI - Effects of combining rapamycin and resveratrol on apoptosis and growth of TSC2
deficient xenograft tumors.
AB - Lymphangioleiomyomatosis (LAM) is a rare neoplastic metastatic disease affecting
women of childbearing age. LAM is caused by hyperactivation of the mechanistic
target of rapamycin complex 1 (mTORC1) as a consequence of tuberous sclerosis
complex (TSC) 1/2 inactivation. Clinically, LAM results in cystic lung
destruction. mTORC1 inhibition using rapamycin analogs (rapalogs) is partially
effective in reducing disease progression and improving lung function. However,
cessation of treatment results in continued progression of the disease. In the
present study, we investigated the effectiveness of the combination of rapamycin
treatment with resveratrol, an autophagy inhibitor, in the TSC2-null xenograft
tumor model. We determined that this combination inhibits phosphatidylinositol
4,5-bisphosphate 3-kinase PI3K/Akt/mTORC1 signaling and activates apoptosis.
Therefore, the combination of rapamycin and resveratrol may be an effective
clinical strategy for treatment of LAM and other diseases with mTORC1
hyperactivation.
PMID- 25844892
TI - Association of definition of acute kidney injury by cystatin C rise with
biomarkers and clinical outcomes in children undergoing cardiac surgery.
AB - IMPORTANCE: Research has identified improved biomarkers of acute kidney injury
(AKI). Cystatin C (CysC) is a better glomerular filtration rate marker than serum
creatinine (SCr) and may improve AKI definition. OBJECTIVE: To determine if
defining clinical AKI by increases in CysC vs SCr alters associations with
biomarkers and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Three-center
prospective cohort study of intensive care units in New Haven, Connecticut,
Cincinnati, Ohio, and Montreal, Quebec, Canada. Participants were 287 patients 18
years or younger without preoperative AKI or end-stage renal disease who were
undergoing cardiac surgery. The study dates were July 1, 2007, through December
31, 2009. EXPOSURES: For biomarker vs clinical AKI associations, the exposures
were first postoperative (0-6 hours after surgery) urine interleukin 18,
neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver
fatty acid-binding protein. For clinical AKI outcome associations, the exposure
was Kidney Disease: Improving Global Outcomes AKI definition (based on SCr or
CysC). MAIN OUTCOMES AND MEASURES: Clinical AKI, length of stay, and length of
mechanical ventilation. We determined areas under the receiver operating
characteristic curve and odds ratios for first postoperative biomarkers to
predict AKI. RESULTS: The SCr-defined vs CysC-defined AKI incidence differed
substantially (43.6% vs 20.6%). Percentage agreement was 71% (kappa = 0.38);
stage 2 or worse AKI percentage agreement was 95%. Interleukin 18 and kidney
injury molecule 1 discriminated for CysC-defined AKI better than for SCr-defined
AKI. For interleukin 18 and kidney injury molecule 1, the areas under the
receiver operating characteristic curve were 0.74 and 0.65, respectively, for
CysC-defined AKI, and 0.66 and 0.58, respectively, for SCr-defined AKI. Fifth (vs
first) quintile concentrations of both biomarkers were more strongly associated
with CysC-defined AKI. For interleukin 18 and kidney injury molecule 1, the odds
ratios were 16.19 (95% CI, 3.55-73.93) and 6.93 (95% CI, 1.88-25.59),
respectively, for CysC-defined AKI vs 6.60 (95% CI, 2.76-15.76) and 2.04 (95% CI,
0.94-4.38), respectively, for SCr-defined AKI. Neutrophil gelatinase-associated
lipocalin and liver fatty acid-binding protein associations with both definitions
were similar. The CysC definitions and SCr definitions were similarly associated
with clinical outcomes of resource use. CONCLUSIONS AND RELEVANCE: Compared with
the SCr-based definition, the CysC-based definition is more strongly associated
with urine interleukin 18 and kidney injury molecule 1 in children undergoing
cardiac surgery. Consideration should be made for defining AKI based on CysC in
clinical care and future studies.
PMID- 25844893
TI - Catalytic mesoporous Janus nanomotors for active cargo delivery.
AB - We report on the synergy between catalytic propulsion and mesoporous silica
nanoparticles (MSNPs) for the design of Janus nanomotors as active cargo delivery
systems with sizes <100 nm (40, 65, and 90 nm). The Janus asymmetry of the
nanomotors is given by electron beam (e-beam) deposition of a very thin platinum
(2 nm) layer on MSNPs. The chemically powered Janus nanomotors present active
diffusion at low H2O2 fuel concentration (i.e., <3 wt %). Their apparent
diffusion coefficient is enhanced up to 100% compared to their Brownian motion.
Due to their mesoporous architecture and small dimensions, they can load cargo
molecules in large quantity and serve as active nanocarriers for directed cargo
delivery on a chip.
PMID- 25844894
TI - Triangular gold nanoplate growth by oriented attachment of Au seeds generated by
strong field laser reduction.
AB - The synthesis of surfactant-free Au nanoplates is desirable for the development
of biocompatible therapeutics/diagnostics. Rapid Delta-function energy deposition
by irradiation of aqueous KAuCl4 solution with a 5 s burst of intense shaped
laser pulses, followed by slow addition of H2O2, results in selective formation
of nanoplates with no additional reagents. The primary mechanism of nanoplate
formation is found to be oriented attachment of the spherical seeds, which self
recrystallize to form crystalline Au nanoplates.
PMID- 25844896
TI - Self-Assembly of PS-b-PDMS on a Tunable PDMS Template with Nanoscale Channels and
Enhanced Anisotropic Wetting.
AB - In this article, we systematically studied the self-assembly of poly(styrene
block-dimethylsiloxane) (PS-b-PDMS) on a poly(dimethylsiloxane) (PDMS) substrate
with nanoscale channels. The channeled PDMS substrate was achieved by a simple
replica molding method. To decrease the effect that the subsequent solvent
treatments had in distorting the soft PDMS substrate, a simple UV/O3 treatment
was provided before the self-assembly, resulting in a relatively stable, harder
and hydrophilic silicon oxide (SiO2) layer on the channeled PDMS surface.
Ultimately, the isotropic SiO2 nanopatterns with spherical and long cylindrical
morphologies were successfully fabricated by the self-assembly of two kinds of PS
b-PDMS on the PDMS substrate with nanoscale channels, respectively. In
particular, we demonstrated that the introduction of isotropic SiO2 patterns is
an effective approach to greatly enhance anisotropic wetting rather than that of
the anisotropic structure with channels.
PMID- 25844895
TI - Discovery of tricyclic indoles that potently inhibit Mcl-1 using fragment-based
methods and structure-based design.
AB - Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of
proteins that is overexpressed and amplified in many cancers. Overexpression of
Mcl-1 allows cancer cells to evade apoptosis and contributes to the resistance of
cancer cells to be effectively treated with various chemotherapies. From an NMR
based screen of a large fragment library, several distinct chemical scaffolds
that bind to Mcl-1 were discovered. Here, we describe the discovery of potent
tricyclic 2-indole carboxylic acid inhibitors that exhibit single digit nanomolar
binding affinity to Mcl-1 and greater than 1700-fold selectivity over Bcl-xL and
greater than 100-fold selectivity over Bcl-2. X-ray structures of these compounds
when complexed to Mcl-1 provide detailed information on how these small-molecules
bind to the target, which was used to guide compound optimization.
PMID- 25844897
TI - Quantification of mutant huntingtin protein in cerebrospinal fluid from
Huntington's disease patients.
AB - BACKGROUND: Quantification of disease-associated proteins in the cerebrospinal
fluid (CSF) has been critical for the study and treatment of several
neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause
of Huntington's disease (HD), is at very low levels in CSF and, to our knowledge,
has never been measured previously. METHODS: We developed an ultrasensitive
single-molecule counting (SMC) mHTT immunoassay that was used to quantify mHTT
levels in CSF samples from individuals bearing the HD mutation and from control
individuals in 2 independent cohorts. RESULTS: This SMC mHTT immunoassay
demonstrated high specificity for mHTT, high sensitivity with a femtomolar
detection threshold, and a broad dynamic range. Analysis of the CSF samples
showed that mHTT was undetectable in CSF from all controls but quantifiable in
nearly all mutation carriers. The mHTT concentration in CSF was approximately 3
fold higher in patients with manifest HD than in premanifest mutation carriers.
Moreover, mHTT levels increased as the disease progressed and were associated
with 5-year onset probability. The mHTT concentration independently predicted
cognitive and motor dysfunction. Furthermore, the level of mHTT was associated
with the concentrations of tau and neurofilament light chain in the CSF,
suggesting a neuronal origin for the detected mHTT. CONCLUSIONS: We have
demonstrated that mHTT can be quantified in CSF from HD patients using the
described SMC mHTT immunoassay. Moreover, the level of mHTT detected is
associated with proximity to disease onset and diminished cognitive and motor
function. The ability to quantify CSF mHTT will facilitate the study of HD, and
mHTT quantification could potentially serve as a biomarker for the development
and testing of experimental mHTT-lowering therapies for HD. TRIAL REGISTRATION:
Not applicable. FUNDING: CHDI Foundation Inc.; Medical Research Council (MRC) UK;
National Institutes for Health Research (NIHR); Rosetrees Trust; Swedish Research
Council; and Knut and Alice Wallenberg Foundation.
PMID- 25844898
TI - Sec63 and Xbp1 regulate IRE1alpha activity and polycystic disease severity.
AB - The HSP40 cochaperone SEC63 is associated with the SEC61 translocon complex in
the ER. Mutations in the gene encoding SEC63 cause polycystic liver disease in
humans; however, it is not clear how altered SEC63 influences disease
manifestations. In mice, loss of SEC63 induces cyst formation both in liver and
kidney as the result of reduced polycystin-1 (PC1). Here we report that
inactivation of SEC63 induces an unfolded protein response (UPR) pathway that is
protective against cyst formation. Specifically, using murine genetic models, we
determined that SEC63 deficiency selectively activates the IRE1alpha-XBP1 branch
of UPR and that SEC63 exists in a complex with PC1. Concomitant inactivation of
both SEC63 and XBP1 exacerbated the polycystic kidney phenotype in mice by
markedly suppressing cleavage at the G protein-coupled receptor proteolysis site
(GPS) in PC1. Enforced expression of spliced XBP1 (XBP1s) enhanced GPS cleavage
of PC1 in SEC63-deficient cells, and XBP1 overexpression in vivo ameliorated
cystic disease in a murine model with reduced PC1 function that is unrelated to
SEC63 inactivation. Collectively, the findings show that SEC63 function regulates
IRE1alpha/XBP1 activation, SEC63 and XBP1 are required for GPS cleavage and
maturation of PC1, and activation of XBP1 can protect against polycystic disease
in the setting of impaired biogenesis of PC1.
PMID- 25844899
TI - Calcium release channel RyR2 regulates insulin release and glucose homeostasis.
AB - The type 2 ryanodine receptor (RyR2) is a Ca2+ release channel on the endoplasmic
reticulum (ER) of several types of cells, including cardiomyocytes and pancreatic
beta cells. In cardiomyocytes, RyR2-dependent Ca2+ release is critical for
excitation-contraction coupling; however, a functional role for RyR2 in beta cell
insulin secretion and diabetes mellitus remains controversial. Here, we took
advantage of rare RyR2 mutations that were identified in patients with a genetic
form of exercise-induced sudden death (catecholaminergic polymorphic ventricular
tachycardia [CPVT]). As these mutations result in a "leaky" RyR2 channel, we
exploited them to assess RyR2 channel function in beta cell dynamics. We
discovered that CPVT patients with mutant leaky RyR2 present with glucose
intolerance, which was heretofore unappreciated. In mice, transgenic expression
of CPVT-associated RyR2 resulted in impaired glucose homeostasis, and an in-depth
evaluation of pancreatic islets and beta cells from these animals revealed
intracellular Ca2+ leak via oxidized and nitrosylated RyR2 channels, activated ER
stress response, mitochondrial dysfunction, and decreased fuel-stimulated insulin
release. Additionally, we verified the effects of the pharmacological inhibition
of intracellular Ca2+ leak in CPVT-associated RyR2-expressing mice, in human
islets from diabetic patients, and in an established murine model of type 2
diabetes mellitus. Taken together, our data indicate that RyR2 channels play a
crucial role in the regulation of insulin secretion and glucose homeostasis.
PMID- 25844900
TI - An epigenetically distinct breast cancer cell subpopulation promotes collective
invasion.
AB - Tumor cells can engage in a process called collective invasion, in which cohesive
groups of cells invade through interstitial tissue. Here, we identified an
epigenetically distinct subpopulation of breast tumor cells that have an enhanced
capacity to collectively invade. Analysis of spheroid invasion in an organotypic
culture system revealed that these "trailblazer" cells are capable of initiating
collective invasion and promote non-trailblazer cell invasion, indicating a
commensal relationship among subpopulations within heterogenous tumors. Canonical
mesenchymal markers were not sufficient to distinguish trailblazer cells from non
trailblazer cells, suggesting that defining the molecular underpinnings of the
trailblazer phenotype could reveal collective invasion-specific mechanisms.
Functional analysis determined that DOCK10, ITGA11, DAB2, PDFGRA, VASN, PPAP2B,
and LPAR1 are highly expressed in trailblazer cells and required to initiate
collective invasion, with DOCK10 essential for metastasis. In patients with
triple-negative breast cancer, expression of these 7 genes correlated with poor
outcome. Together, our results indicate that spontaneous conversion of the
epigenetic state in a subpopulation of cells can promote a transition from in
situ to invasive growth through induction of a cooperative form of collective
invasion and suggest that therapeutic inhibition of trailblazer cell invasion may
help prevent metastasis.
PMID- 25844903
TI - Stable nanoparticles prepared by heating electrostatic complexes of whey protein
isolate-dextran conjugate and chondroitin sulfate.
AB - A simple and green method was developed for preparing the stable biopolymer
nanoparticles with pH and salt resistance. The method involved the macromolecular
crowding Maillard process and heat-induced gelation process. The conjugates of
whey protein isolate (WPI) and dextran were produced by Maillard reaction. The
nanoparticles were fabricated by heating electrostatic complexes of WPI-dextran
conjugate and chondroitin sulfate (ChS) above the denaturation temperature and
near the isoelectric point of WPI. Then, the nanoparticles were characterized by
spectrophotometry, dynamic laser scattering, zeta potential, transmission
electron microscopy, atomic force microscopy, and scanning electron microscopy.
Results showed that the nanoparticles were stable in the pH range from 1.0 to 8.0
and in the presence of high salt concentration of 200 mM NaCl. WPI-dextran
conjugate, WPI, and ChS were assembled into the nanoparticles with dextran
conjugated to WPI/ChS shell and WPI/ChS core. The repulsive steric interactions,
from both dextran covalently conjugated to WPI and ChS electrostatically
interacted with WPI, were the major formation mechanism of the stable
nanoparticles. As a nutrient model, lutein could be effectively encapsulated into
the nanoparticles. Additionally, the nanoparticles exhibited a spherical shape
and homogeneous size distribution regardless of lutein loading. The results
suggested that the stable nanoparticles from proteins and strong polyelectrolyte
polysaccharides would be used as a promising target delivery system for
hydrophobic nutrients and drugs at physiological pH and salt conditions.
PMID- 25844904
TI - Automatic detection of confusion in elderly users of a web-based health
instruction video.
AB - BACKGROUND: Because of cognitive limitations and lower health literacy, many
elderly patients have difficulty understanding verbal medical instructions.
Automatic detection of facial movements provides a nonintrusive basis for
building technological tools supporting confusion detection in healthcare
delivery applications on the Internet. MATERIALS AND METHODS: Twenty-four elderly
participants (70-90 years old) were recorded while watching Web-based health
instruction videos involving easy and complex medical terminology. Relevant
fragments of the participants' facial expressions were rated by 40 medical
students for perceived level of confusion and analyzed with automatic software
for facial movement recognition. RESULTS: A computer classification of the
automatically detected facial features performed more accurately and with a
higher sensitivity than the human observers (automatic detection and
classification, 64% accuracy, 0.64 sensitivity; human observers, 41% accuracy,
0.43 sensitivity). A drill-down analysis of cues to confusion indicated the
importance of the eye and eyebrow region. CONCLUSIONS: Confusion caused by
misunderstanding of medical terminology is signaled by facial cues that can be
automatically detected with currently available facial expression detection
technology. The findings are relevant for the development of Web-based services
for healthcare consumers.
PMID- 25844901
TI - 12/15-Lipoxygenase-mediated enzymatic lipid oxidation regulates DC maturation and
function.
AB - DCs are able to undergo rapid maturation, which subsequently allows them to
initiate and orchestrate T cell-driven immune responses. DC maturation must be
tightly controlled in order to avoid random T cell activation and development of
autoimmunity. Here, we determined that 12/15-lipoxygenase-meditated (12/15-LO
mediated) enzymatic lipid oxidation regulates DC activation and fine-tunes
consecutive T cell responses. Specifically, 12/15-LO activity determined the DC
activation threshold via generation of phospholipid oxidation products that
induced an antioxidative response dependent on the transcription factor NRF2.
Deletion of the 12/15-LO-encoding gene or pharmacologic inhibition of 12/15-LO in
murine or human DCs accelerated maturation and shifted the cytokine profile,
thereby favoring the differentiation of Th17 cells. Exposure of 12/15-LO
deficient DCs to 12/15-LO-derived oxidized phospholipids attenuated both DC
activation and the development of Th17 cells. Analysis of lymphatic tissues from
12/15-LO-deficient mice confirmed enhanced maturation of DCs as well as an
increased differentiation of Th17 cells. Moreover, experimental autoimmune
encephalomyelitis in mice lacking 12/15-LO resulted in an exacerbated Th17-driven
autoimmune disease. Together, our data reveal that 12/15-LO controls maturation
of DCs and implicate enzymatic lipid oxidation in shaping the adaptive immune
response.
PMID- 25844902
TI - Gq signaling causes glomerular injury by activating TRPC6.
AB - Familial forms of focal segmental glomerulosclerosis (FSGS) have been linked to
gain-of-function mutations in the gene encoding the transient receptor potential
channel C6 (TRPC6). GPCRs coupled to Gq signaling activate TRPC6, suggesting that
Gq-dependent TRPC6 activation underlies glomerular diseases. Here, we developed a
murine model in which a constitutively active Gq alpha subunit (Gq(Q209L),
referred to herein as GqQ>L) is specifically expressed in podocytes and examined
the effects of this mutation in response to puromycin aminonucleoside (PAN)
nephrosis. We found that compared with control animals, animals expressing GqQ>L
exhibited robust albuminuria, structural features of FSGS, and reduced numbers of
glomerular podocytes. Gq activation stimulated calcineurin (CN) activity,
resulting in CN-dependent upregulation of TRPC6 in murine kidneys. Deletion of
TRPC6 in GqQ>L-expressing mice prevented FSGS development and inhibited both
tubular damage and podocyte loss induced by PAN nephrosis. Similarly,
administration of the CN inhibitor FK506 reduced proteinuria and tubular injury
but had more modest effects on glomerular pathology and podocyte numbers in
animals with constitutive Gq activation. Moreover, these Gq-dependent effects on
podocyte injury were generalizable to diabetic kidney disease, as expression of
GqQ>L promoted albuminuria, mesangial expansion, and increased glomerular
basement membrane width in diabetic mice. Together, these results suggest that
targeting Gq/TRPC6 signaling may have therapeutic benefits for the treatment of
glomerular diseases.
PMID- 25844905
TI - Trust in deliberation: The consequences of deliberative decision strategies for
medical decisions.
AB - OBJECTIVE: Decision aids (DAs) play an increasingly critical role in supporting
patients in making preference-sensitive treatment decisions. One largely untested
assumption of DA design is that patients should be encouraged to deliberate
carefully about their options after being informed of those options. The purpose
of the present research is to test the impact of deliberative versus intuitive
decision strategies in medical decision contexts. METHOD: In 3 experiments,
participants were randomly assigned to make a hypothetical medical decision
either intuitively, or using various deliberative strategies. In Study 1, we
predicted that deliberation would improve decision confidence while not changing
decisions. In Study 2, our aim was to establish whether the observed increase in
confidence was due to decision-making effort, confirmation bias, or both. In
Study 3, it was predicted that deliberation would cause participants to become
more confident in suboptimal decisions. RESULTS: Across 3 studies, participants
who deliberated felt better about their decisions and decision process, even when
the decision was the same as what would have been chosen intuitively (Studies 1
and 2), and even when the decision was normatively bad (Study 3). Study 2
additionally indicated that participants' confidence was driven by confirmation
bias rather than effort justification. CONCLUSIONS: Deliberative tasks may often
fail to be an effective debiasing tool, and components of patient decision aids
that ask patients to deliberate may serve to improve how patients feel without
improving the quality of their decisions.
PMID- 25844906
TI - Association between trajectories of maternal depression and subsequent
psychological functioning in youth with and without chronic physical illness.
AB - OBJECTIVES: The aim of this study was to determine if the presence of youth
chronic illness moderates the association between trajectories of maternal
depressive symptoms and psychological functioning in youths. METHODS: Data came
from the National Longitudinal Survey of Children and Youth (N = 11,813). Using
the 12-item version of the Center for Epidemiological Studies Depression Scale
(CES-D), symptom trajectories were estimated by latent class growth modeling over
3 measurement occasions (when their children were 10-11, 12-13, and 14-15 years).
The moderating effect of youth chronic illness on the association between
maternal depression and youth psychological functioning at 16-19 years was tested
using multiple regression. Three measures of psychological functioning were
assessed: anger regulation (Bar-On Emotional Quotient Inventory), self-concept
(Self-Determination Questionnaire), and depressive symptoms (CES-D). RESULTS:
Four trajectories (low, decreasing, increasing, high) of maternal depression were
identified. The association of maternal depressive symptoms on youth
psychological functioning was modified by chronic illness; less favorable
trajectories of maternal depression had a more pronounced detrimental association
on youths with chronic illness compared to controls. CONCLUSIONS: Youths with
chronic illness are particularly vulnerable to the negative psychological
exposure of maternal depressive symptoms during the transition to adulthood.
Family-centered transition of care programs in the medical setting may be
beneficial in reducing the association between symptoms of maternal depression
and youth psychological functioning.
PMID- 25844907
TI - Relationships among spousal communication, self-efficacy, and motivation among
expectant Latino fathers who smoke.
AB - OBJECTIVE: Cigarette smoking is a prevalent problem among Latinos, yet little is
known about what factors motivate them to quit smoking or make them feel more
confident that they can. Given cultural emphases on familial bonds among Latinos
(e.g., familismo), it is possible that communication processes among Latino
spouses play an important role. The present study tested a mechanistic model in
which perceived spousal constructive communication patterns predicted changes in
level of motivation for smoking cessation through changes in self-efficacy among
Latino expectant fathers. METHODS: Latino males (n = 173) and their pregnant
partners participated in a couple-based intervention targeting males' smoking.
Couples completed self-report measures of constructive communication, self
efficacy (male partners only), and motivation to quit (male partners only) at 4
time points throughout the intervention. RESULTS: Higher levels of perceived
constructive communication among Latino male partners predicted subsequent
increases in male partners' self-efficacy and, to a lesser degree, motivation to
quit smoking; however, self-efficacy did not mediate associations between
constructive communication and motivation to quit smoking. Furthermore, positive
relationships with communication were only significant at measurements taken
after completion of the intervention. Female partners' level of perceived
constructive communication did not predict male partners' outcomes. CONCLUSION:
These results provide preliminary evidence to support the utility of couple-based
interventions for Latino men who smoke. Findings also suggest that perceptions of
communication processes among Latino partners (particularly male partners) may be
an important target for interventions aimed at increasing desire and perceived
ability to quit smoking among Latino men. (PsycINFO Database Record
PMID- 25844908
TI - Leadership styles, emotion regulation, and burnout.
AB - This study investigated the potential impact of leadership style on leaders'
emotional regulation strategies and burnout. Drawing on the full-range model of
leadership and Conservation of Resources (COR) theory, we tested whether
transformational, contingent reward, management by exception-active and -passive,
or laissez-faire leadership exert direct effects on leaders' reported use of
surface acting, deep acting, and genuine emotion. In turn, we hypothesized and
tested the indirect effect of leadership on burnout through surface acting. Three
waves of data from 205 leaders were analyzed using OLS regression.
Transformational leadership predicted deep acting and genuine emotion. Contingent
reward predicted both surface and deep acting. Management by exception-active and
-passive predicted surface acting, and laissez faire predicted genuine emotion.
The indirect effects of management by exception-active and -passive on burnout
through surface acting were not significant. Indirect effects of transformational
leadership and laissez-faire on burnout through genuine emotion, however, were
significant. This study provides empirical evidence for the hypothesized
relationships between leadership style, emotion regulation, and burnout, and
provides the basis for future research and theory building on this topic.
PMID- 25844909
TI - Managing disclosure of personal information: An opportunity to enhance supported
employment.
AB - OBJECTIVE: To first provide an overview of studies that explore mental health
disclosure in the workplace; including factors that influence the decision to
disclose, and differing approaches to disclosure (binary, multidimensional, and
evolving and ongoing). Second, to provide a critical overview of existing tools
designed to help clients manage their mental health disclosure decisions. METHOD:
Electronic searches of PubMed, PsycINFO and ScienceDirect were undertaken,
excluding all articles published prior to 1990. The following search terms were
used: mental health disclosure, employment, severe and persistent mental illness,
psychosis, schizophrenia, supported employment, individual placement and support
(IPS). RESULTS: We found that mental health disclosure involves a complex
decision-making process, and yet clients of IPS supported employment are
currently provided with little structured guidance on how to manage their
personal information in the workplace. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
More extensive investigations are required of existing mental health disclosure
tools before they can be developed into a standardized intervention for
practitioners. However, preliminary evidence suggests that facilitating better
disclosure decisions and management of personal information is a promising area
of future research. This line of investigation is likely to find ways to enhance
competitive employment outcomes in supported employment for people with severe
and persistent mental illness.
PMID- 25844911
TI - Stress-related personal growth among emerging adults whose mothers have been
diagnosed with mental illness.
AB - OBJECTIVE: This study explored whether emerging adults' reports of their
relationships with their mothers who have been diagnosed with mental illness and
their attempts to make meaning of the experience of having a mother with mental
illness were associated with stress-related personal growth. METHODS: Fifty-two
emerging adult children with mothers who have been diagnosed with mental illness
responded to a self-report questionnaire containing measures of adult parent
child relationships, meaning making, and stress-related personal growth. RESULTS:
Hierarchical multiple linear regression analysis of the cross-sectional data
indicated that meaning making contributed to stress-related personal growth after
accounting for emerging adult-mother relationship factors. Aspects of the
emerging adult-mother relationship did not contribute to growth. CONCLUSIONS:
Efforts to make meaning of having a mother with mental illness may facilitate
growth among emerging adult children. Longitudinal investigations in larger
samples are needed to better understand the relationship among interpersonal
relationships, meaning making, and growth in this population. IMPLICATIONS FOR
PRACTICE: Interventions with adult children of people with mental illness should
address their capacity for personal growth.
PMID- 25844910
TI - From discrimination to internalized mental illness stigma: The mediating roles of
anticipated discrimination and anticipated stigma.
AB - OBJECTIVE: Internalizing mental illness stigma is related to poorer well-being,
but less is known about the factors that predict levels of internalized stigma.
This study explored how experiences of discrimination relate to greater
anticipation of discrimination and devaluation in the future and how anticipation
of stigma in turn predicts greater stigma internalization. METHOD: Participants
were 105 adults with mental illness who self-reported their experiences of
discrimination based on their mental illness, their anticipation of
discrimination and social devaluation from others in the future, and their level
of internalized stigma. Participants were approached in several locations and
completed surveys on laptop computers. RESULTS: Correlational analyses indicated
that more experiences of discrimination due to one's mental illness were related
to increased anticipated discrimination in the future, increased anticipated
social stigma from others, and greater internalized stigma. Multiple serial
mediator analyses showed that the effect of experiences of discrimination on
internalized stigma was fully mediated by increased anticipated discrimination
and anticipated stigma. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Experiences of
discrimination over one's lifetime may influence not only how much future
discrimination people with mental illness are concerned with but also how much
they internalize negative feelings about the self. Mental health professionals
may need to address concerns with future discrimination and devaluation in order
to decrease internalized stigma.
PMID- 25844912
TI - Next-generation psychiatric assessment: Using smartphone sensors to monitor
behavior and mental health.
AB - OBJECTIVE: Optimal mental health care is dependent upon sensitive and early
detection of mental health problems. We have introduced a state-of-the-art method
for the current study for remote behavioral monitoring that transports assessment
out of the clinic and into the environments in which individuals negotiate their
daily lives. The objective of this study was to examine whether the information
captured with multimodal smartphone sensors can serve as behavioral markers for
one's mental health. We hypothesized that (a) unobtrusively collected smartphone
sensor data would be associated with individuals' daily levels of stress, and (b)
sensor data would be associated with changes in depression, stress, and
subjective loneliness over time. METHOD: A total of 47 young adults (age range:
19-30 years) were recruited for the study. Individuals were enrolled as a single
cohort and participated in the study over a 10-week period. Participants were
provided with smartphones embedded with a range of sensors and software that
enabled continuous tracking of their geospatial activity (using the Global
Positioning System and wireless fidelity), kinesthetic activity (using multiaxial
accelerometers), sleep duration (modeled using device-usage data, accelerometer
inferences, ambient sound features, and ambient light levels), and time spent
proximal to human speech (i.e., speech duration using microphone and speech
detection algorithms). Participants completed daily ratings of stress, as well as
pre- and postmeasures of depression (Patient Health Questionnaire-9; Spitzer,
Kroenke, & Williams, 1999), stress (Perceived Stress Scale; Cohen et al., 1983),
and loneliness (Revised UCLA Loneliness Scale; Russell, Peplau, & Cutrona, 1980).
RESULTS: Mixed-effects linear modeling showed that sensor-derived geospatial
activity (p < .05), sleep duration (p < .05), and variability in geospatial
activity (p < .05), were associated with daily stress levels. Penalized
functional regression showed associations between changes in depression and
sensor-derived speech duration (p < .05), geospatial activity (p < .05), and
sleep duration (p < .05). Changes in loneliness were associated with sensor
derived kinesthetic activity (p < .01). CONCLUSIONS AND IMPLICATIONS FOR
PRACTICE: Smartphones can be harnessed as instruments for unobtrusive monitoring
of several behavioral indicators of mental health. Creative leveraging of
smartphone sensing could provide novel opportunities for close-to-invisible
psychiatric assessment at a scale and efficiency that far exceeds what is
currently feasible with existing assessment technologies.
PMID- 25844913
TI - Factors affecting implementation of an evidence-based practice in the Veterans
Health Administration: Illness management and recovery.
AB - OBJECTIVE: Illness management and recovery (IMR) is an evidence-based practice
that assists consumers in managing their illnesses and pursuing personal recovery
goals. Although research has examined factors affecting IMR implementation
facilitated by multifaceted, active roll-outs, the current study attempted to
elucidate factors affecting IMR implementation outside the context of a research
driven implementation. METHODS: Semi-structured interviews with 20 local recovery
coordinators and 18 local IMR experts were conducted at 23 VA medical centers.
Interviews examined perceived and experienced barriers and facilitators to IMR
implementation. Data were analyzed via thematic inductive/deductive analysis in
the form of crystallization/immersion. RESULTS: Six factors differed between
sites implementing IMR from those not providing IMR: awareness of IMR, importer
champions, autonomy-supporting leadership, veteran-centered care, presence of a
sensitive period, and presence of a psychosocial rehabilitation and recovery
center. Four factors were common in both groups: recovery orientation, evidence
based practices orientation, perceived IMR fit within program structure, and
availability of staff time. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: IMR can be
adopted in lieu of active implementation support; however, knowledge
dissemination appears to be key. Future research should examine factors affecting
the quality of implementation.
PMID- 25844914
TI - How are perceived stigma, self-stigma, and self-reliance related to treatment
seeking? A three-path model.
AB - OBJECTIVE: Many college students may experience mental health problems but do not
seek treatment from mental health professionals. The present study examined how
perceived stigma and self-stigma toward seeking mental health treatment, as well
as perceptions of self-reliance for coping with mental health problems, relate to
college student treatment-seeking. METHOD: In total, 246 students completed a
self-report survey that included measures of perceived stigma and self-stigma for
treatment-seeking, self-reliance for addressing mental health concerns, self
reported mental health problems, symptoms of depression and alcohol-related
problems, attitudes toward treatment-seeking, and treatment-seeking behavior.
RESULTS: Regression analyses revealed that higher perceived stigma, self-stigma,
and self-reliance were all related to a more negative attitude toward treatment
seeking. In a 3-path mediation model, bootstrapping results indicated an indirect
effect where perceived stigma was related to attitude toward treatment-seeking
and treatment-seeking behaviors through self-stigma and self-reliance.
Specifically, higher perceived stigma was related to higher self-stigma, higher
self-stigma was related to higher self-reliance, and higher self-reliance was
associated with a more negative attitude toward treatment-seeking in the overall
sample, and a decreased probability of having sought treatment among those who
screened positive for a mental health problem. CONCLUSIONS AND IMPLICATIONS FOR
PRACTICE: Perceived stigma may influence whether or not college students seek
treatment for mental health problems by potentially increasing stigmatizing
attitudes toward themselves and increasing preferences for handling problems on
their own. Researchers and practitioners are recommended to seek a better
understanding of the complex treatment barriers to reduce stigma and facilitate
treatment-seeking.
PMID- 25844915
TI - The relationship between cognition, job complexity, and employment duration in
first-episode psychosis.
AB - OBJECTIVE: To investigate the relationship between cognition and employment
duration in first-episode psychosis (FEP), and establish if a "fit" between
cognition and job complexity is associated with longer employment duration.
METHOD: This study involved secondary data analysis of a subsample of FEP
individuals (n = 65) who participated in a randomized controlled trial comparing
Individual Placement and Support plus treatment as usual (TAU), versus TAU alone,
over 6 months. A cognitive battery was administered at baseline and employment
duration (hours) and job complexity in the longest held job over 6 months were
measured. RESULTS: Factor analysis with promax rotation of the cognitive battery
revealed 4 cognitive domains: (a) attention and processing speed; (b) verbal
learning and memory; (c) verbal comprehension and fluency; and (d) visual
organization and memory (VO&M). The final hierarchical regression model found
that VO&M and job complexity independently predicted employment duration in
longest held job; however, the "fit" (or interaction) between VO&M and job
complexity was not significant. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: These
findings suggest that VO&M and job complexity are important predictors of
employment duration, but it is not necessary to ensure VO&M ability matches job
complexity. However, there are limited comparative studies in this area, and
other aspects of the person-organization fit perspective may still be useful to
optimize vocational outcomes in FEP.
PMID- 25844917
TI - Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential
Mechanistic Link between Enzyme Superfamilies.
AB - Mandelate racemase (MR), a member of the enolase superfamily, catalyzes the
Mg(2+)-dependent interconversion of the enantiomers of mandelate. Several alpha
keto acids are modest competitive inhibitors of MR [e.g., mesoxalate (Ki = 1.8 +/
0.3 mM) and 3-fluoropyruvate (Ki = 1.3 +/- 0.1 mM)], but, surprisingly, 3
hydroxypyruvate (3-HP) is an irreversible, time-dependent inhibitor (kinact/KI =
83 +/- 8 M(-1) s(-1)). Protection from inactivation by the competitive inhibitor
benzohydroxamate, trypsinolysis and electrospray ionization tandem mass
spectrometry analyses, and X-ray crystallographic studies reveal that 3-HP
undergoes Schiff-base formation with Lys 166 at the active site, followed by
formation of an aldehyde/enol(ate) adduct. Such a reaction is unprecedented in
the enolase superfamily and may be a relic of an activity possessed by a
promiscuous progenitor enzyme. The ability of MR to form and deprotonate a Schiff
base intermediate furnishes a previously unrecognized mechanistic link to other
alpha/beta-barrel enzymes utilizing Schiff-base chemistry and is in accord with
the sequence- and structure-based hypothesis that members of the metal-dependent
enolase superfamily and the Schiff-base-forming N-acetylneuraminate lyase
superfamily and aldolases share a common ancestor.
PMID- 25844916
TI - A pilot study of the Nutrition and Exercise for Wellness and Recovery (NEW-R): A
weight loss program for individuals with serious mental illnesses.
AB - OBJECTIVE: This purpose of this study was to evaluate the Nutrition and Exercise
for Wellness and Recovery (NEW-R) weight loss intervention. METHOD: Using a
pretest/posttest design, 18 participants recruited from a community-based mental
health program were assessed at baseline, immediately following the intervention
(8 weeks), and at 6-month follow-up. The intervention was delivered by an
occupational therapist and occupational therapy graduate students and consisted
of 8 weekly sessions lasting 2 hr. Outcomes included changes in weight, and
levels of knowledge about nutrition and exercise. RESULTS: Participants lost an
average of 3 pounds at immediate postintervention, and lost an average of 10
pounds at the 6-month follow-up. Participants also demonstrated significant
increases in their knowledge about nutrition and physical activity. CONCLUSIONS
AND IMPLICATIONS FOR PRACTICE: The results of this study provide preliminary
support for the impact of the NEW-R intervention on weight loss and knowledge
about diet and exercise.
PMID- 25844918
TI - Porous polystyrene-block-poly(acrylic acid)/hemoglobin membrane formed by dually
driven self-assembly and electrochemical application.
AB - This study demonstrated a facile method to form a porous polymeric membrane,
immobilizing a biocatalyst. A polyelectrolyte-based amphiphilic diblock
copolymer, i.e., polystyrene-block-poly(acrylic acid) (PS-b-PAA), self-assembled
with hemoglobin (Hb) dually driven by charge and amphiphilicity during solution
casting and evaporation. XPS and contact angle measurements suggested that the PS
block enriched on the membrane surface. The PAA block pointed toward the internal
membrane as well as ordered the Hb arrangement at the interface of the polymer
and electrode. The obtained PS-b-PAA/Hb electrode showed a remarkably enhanced
direct electron transfer (ET), which was revealed to be a surface-controlled
process accompanied by single-proton transfer. The membrane was tested to
catalyze the reduction of hydrogen peroxide, and exhibited an excellent
reproducibility and stability. This method with a charge and amphiphilicity
dually driven (CADD) self-assembly opened up a new way to construct a third
generation electrochemical biosensor.
PMID- 25844919
TI - Charge percolation pathways guided by defects in quantum dot solids.
AB - Charge hopping and percolation in quantum dot (QD) solids has been widely
studied, but the microscopic nature of the percolation process is not understood
or determined. Here we present the first imaging of the charge percolation
pathways in two-dimensional PbS QD arrays using Kelvin probe force microscopy
(KPFM). We show that under dark conditions electrons percolate via in-gap states
(IGS) instead of the conduction band, while holes percolate via valence band
states. This novel transport behavior is explained by the electronic structure
and energy level alignment of the individual QDs, which was measured by scanning
tunneling spectroscopy (STS). Chemical treatments with hydrazine can remove the
IGS, resulting in an intrinsic defect-free semiconductor, as revealed by STS and
surface potential spectroscopy. The control over IGS can guide the design of
novel electronic devices with impurity conduction, and photodiodes with
controlled doping.
PMID- 25844921
TI - Mapping pixel dissimilarity in wide-field super-resolution fluorescence
microscopy.
AB - Recent advances in fluorescence bioimaging with single-molecule sensitivity have
relied on the analysis and visualization of single-molecule data obtained on
smart fluorophores. We describe an alternative method to enhance the information
content of densely labeled fluorescence images. Visualization is improved by
representing pixels as the dissimilarities of the fluctuations of the
fluorescence signals, with the dissimilarity being taken to the mean of the
signals over all the pixels. Mapping pixel dissimilarity (Mappix) results in
signal and information enhancement of the output images. In addition, the spatial
distribution of the fluorescence brightness of the original image is not skewed.
This allows large differences of molecular brightness to be handled which turns
out to be critical to the fidelity of the final image. In this work, we provide
testing of the Mappix approach with both simulated and real data. The results
obtained on HEK cells expressing Dronpa photoswitchable fluorescent protein show
that, for densely labeled samples, improvement can be obtained on fluorescence
images allowing the observation of structural information. Despite some
limitations, comparison to state of art methods reveals that Mappix can be very
useful for biological imaging applications.
PMID- 25844922
TI - Probing the Effect of miRNA on siRNA-PEI Polyplexes.
AB - Delivery of small interfering RNA (siRNA) for silencing of aberrantly expressed
genes is a promising therapy for the treatment of various genetic disorders.
Polymeric carriers have been used in the design of efficient delivery systems to
generate nanoscale siRNA polyplexes. Despite the great amount of research pursued
on siRNA therapeutics, the underlying mechanisms of polyplex dissociation in
cytosol are still unclear. The fate of siRNA polyplexes during intracellular
stages of delivery and how the endogenous molecules may affect the integrity of
polyplexes remains to be explored. In this study, we have focused on miRNA-21 as
a representative anionic endogenous molecule and performed gel electrophoresis
mobility shift assays, particle size and zeta (zeta)-potential analyses, and a
series of all-atom molecular dynamics simulations to elucidate the effect of
miRNA on siRNA-PEI polyplexes. We report a slightly better binding to PEI by
miRNA than that of siRNA, and speculated that miRNA may disrupt the integrity of
preformed siRNA-PEI polyplexes. In contrast to our initial speculation, however,
introduction of miRNA to a preformed siRNA-PEI polyplex revealed formation of a
miRNA layer surrounding the polyplex through interactions with PEI. The resulting
structure is a ternary siRNA-PEI-miRNA complex, where the experimentally
determined zeta-potential was found to decrease as a function of miRNA added.
PMID- 25844923
TI - Alkali-templated surface nanopatterning of chalcogenide thin films: a novel
approach toward solar cells with enhanced efficiency.
AB - Concepts of localized contacts and junctions through surface passivation layers
are already advantageously applied in Si wafer-based photovoltaic technologies.
For Cu(In,Ga)Se2 thin film solar cells, such concepts are generally not applied,
especially at the heterojunction, because of the lack of a simple method yielding
features with the required size and distribution. Here, we show a novel,
innovative surface nanopatterning approach to form homogeneously distributed
nanostructures (<30 nm) on the faceted, rough surface of polycrystalline
chalcogenide thin films. The method, based on selective dissolution of self
assembled and well-defined alkali condensates in water, opens up new research
opportunities toward development of thin film solar cells with enhanced
efficiency.
PMID- 25844924
TI - Application of a high-throughput analyzer in evaluating solid adsorbents for post
combustion carbon capture via multicomponent adsorption of CO2, N2, and H2O.
AB - Despite the large number of metal-organic frameworks that have been studied in
the context of post-combustion carbon capture, adsorption equilibria of gas
mixtures including CO2, N2, and H2O, which are the three biggest components of
the flue gas emanating from a coal- or natural gas-fired power plant, have never
been reported. Here, we disclose the design and validation of a high-throughput
multicomponent adsorption instrument that can measure equilibrium adsorption
isotherms for mixtures of gases at conditions that are representative of an
actual flue gas from a power plant. This instrument is used to study 15 different
metal-organic frameworks, zeolites, mesoporous silicas, and activated carbons
representative of the broad range of solid adsorbents that have received
attention for CO2 capture. While the multicomponent results presented in this
work provide many interesting fundamental insights, only adsorbents
functionalized with alkylamines are shown to have any significant CO2 capacity in
the presence of N2 and H2O at equilibrium partial pressures similar to those
expected in a carbon capture process. Most significantly, the amine-appended
metal organic framework mmen-Mg2(dobpdc) (mmen = N,N'-dimethylethylenediamine,
dobpdc (4-) = 4,4'-dioxido-3,3'-biphenyldicarboxylate) exhibits a record CO2
capacity of 4.2 +/- 0.2 mmol/g (16 wt %) at 0.1 bar and 40 degrees C in the
presence of a high partial pressure of H2O.
PMID- 25844925
TI - Life cycle assessment of a novel closed-containment salmon aquaculture
technology.
AB - In salmonid aquaculture, a variety of technologies have been deployed that
attempt to limit a range of environmental impacts associated with net-pen
culture. One such technology employs a floating, solid-walled enclosure as the
primary culture environment, providing greater potential control over negative
interactions with surroundings waters while limiting energy use required for
water circulation, thermo-regulation and supplemental oxygen provision. Here, we
utilize life cycle assessment to model contributions to a suite of global-scale
resource depletion and environmental concerns (including global warming
potential, acidification potential, marine eutrophication potential, cumulative
energy use, and biotic resource use) of such a technology deployed commercially
to rear Chinook salmon in coastal British Columbia, Canada. Results indicate that
at full grow-out, feed provisioning and on-site energy use dominate contributions
across four of five impact categories assessed. For example, per tonne of salmon
harvested, feed contributed approximately 72% to global warming potential, 72% to
acidification potential, and accounted for 100% of biotic resource use. However,
for both feed and on-site energy use, impacts are heavily influenced by specific
sources of inputs; therefore efforts to improve the environmental performance of
this technology should focus on reducing these in favor of less impactful
alternatives.
PMID- 25844927
TI - I will speak up if my voice is socially desirable: A moderated mediating process
of promotive versus prohibitive voice.
AB - Employees are likely to speak up if they perceive high efficacy and low risk
associated with such behavior, that is, if they perceive voice is socially
desirable. Drawing on socially desirable responding (SDR) theory, we reason that
individual value on power distance and supervisory delegation are related to the
agentic motive for SDR, and that these 2 factors interact to influence employees'
perceived efficacy of voice. We also identify individual value on superficial
harmony and group voice climate, which are both relevant to the communal motive
for SDR, jointly affect perceived risk of voice. Furthermore, by influencing
perceived efficacy and perceived risk, these interactive forces would be
differentially related to promotive versus prohibitive voice. Data from 66 middle
managers and 262 of their direct reports in 5 high-tech firms provide
considerable support for our hypothesized moderated mediation model. Supervisory
delegation weakens the negative relationship between power distance and perceived
efficacy of promotive voice, and the indirect relationship between power distance
and promotive voice via perceived efficacy. In contrast, group voice climate
weakens the positive relationship between superficial harmony and perceived risk
of prohibitive voice, which mediates the indirect relationship between
superficial harmony and prohibitive voice. We discuss the theoretical and
practical implications of our findings in organizational settings.
PMID- 25844926
TI - Developmental regulation and induction of cytochrome P450 2W1, an enzyme
expressed in colon tumors.
AB - Cytochrome P450 2W1 (CYP2W1) is expressed predominantly in colorectal and also in
hepatic tumors, whereas the levels are insignificant in the corresponding normal
human adult tissues. CYP2W1 has been proposed as an attractive target for
colorectal cancer (CRC) therapy by exploiting its ability to activate duocarmycin
prodrugs to cytotoxic metabolites. However, its endogenous function, regulation
and developmental pattern of expression remain unexplored. Here we report the
CYP2W1 developmental expression in the murine and human gastrointestinal tissues.
The gene expression in the colon and small intestine commence at early stages of
embryonic life and is completely silenced shortly after the birth.
Immunohistochemical analysis of human fetal colon revealed that CYP2W1 expression
is restricted to the crypt cells. The silencing of CYP2W1 after birth correlates
with the increased methylation of CpG-rich regions in both murine and human
CYP2W1 genes. Analysis of CYP2W1 expression in the colon adenocarcinoma cell line
HCC2998 revealed that the gene expression can be induced by e.g. the antitumor
agent imatinib, linoleic acid and its derivatives. The imatinib mediated
induction of CYP2W1 suggests an adjuvant therapy to treatment with duocarmycins
that thus would involve induction of tumor CYP2W1 levels followed by the CYP2W1
activated duocarmycin prodrugs. Taken together these data strongly support
further exploration of CYP2W1 as a specific drug target in CRC.
PMID- 25844929
TI - The Coupling between Gold or Silver Nanocubes in Their Homo-Dimers: A New
Coupling Mechanism at Short Separation Distances.
AB - Using the DDA method, we investigated the near-field coupling between two excited
Au or Ag 42 nm nanocubes in a face-to-face dimer configuration at small
separation distances where the exponential coupling behavior distinctly changes.
This could be due to the failure of the dipole approximation at short distances
or a change in the electromagnetic field distribution between the adjacent
monomers. A detailed calculation of the plasmonic field distribution strongly
suggests that the latter mechanism is responsible for the failure of the expected
exponential coupling behavior at small separation distances. The results suggest
that the observed optical properties of the pair of Au or Ag nanocubes separated
by distances larger than 6 nm, result from the electromagnetic coupling between
the oscillating dipoles at the corners of the adjacent facets of the nanocubes.
At separations smaller than 6 nm, the distribution of the plasmonic dipoles along
both the facets and the corners of the adjacent monomers control the plasmonic
spectra and the distance dependent optical properties of the dimer.
PMID- 25844928
TI - The molecular epidemiology of Treponema pallidum subspecies pallidum.
AB - Pathogens adapt and evolve in response to pressures exerted by host environments,
leading to generation of genetically diverse variants. Treponema pallidum
subspecies pallidum displays a substantial amount of interstrain diversity. These
variants have been identified in various parts of the world, indicating
transmission linkage between geographical regions. Genotyping is based on
molecular characterisation of various loci in the syphilis treponeme genome, but
still require further development and continued research, as new bacterial types
are continually being detected. The goal for studying the molecular epidemiology
of Treponema pallidum variants is the global monitoring of the transmission of
genetically distinct organisms with different drug sensitivities and,
potentially, different virulence proprieties.
PMID- 25844931
TI - High-Yield and Selective Photoelectrocatalytic Reduction of CO2 to Formate by
Metallic Copper Decorated Co3O4 Nanotube Arrays.
AB - Carbon dioxide (CO2) reduction to useful chemicals is of great significance to
global climate and energy supply. In this study, CO2 has been
photoelectrocatalytically reduced to formate at metallic Cu nanoparticles (Cu
NPs) decorated Co3O4 nanotube arrays (NTs) with high yield and high selectivity
of nearly 100%. Noticeably, up to 6.75 mmol.L(-1).cm(-2) of formate was produced
in an 8 h photoelectrochemical process, representing one of the highest yields
among those in the literature. The results of scanning electron microscopy,
transmission electron microscopy and photoelectrochemical characterization
demonstrated that the enhanced production of formate was attributable to the self
supported Co3O4 NTs/Co structure and the interface band structure of Co3O4 NTs
and metallic Cu NPs. Furthermore, a possible two-electron reduction mechanism on
the selective PEC CO2 reduction to formate at the Cu-Co3O4 NTs was explored. The
first electron reduction intermediate, CO2 ads*-, was adsorbed on Cu in the form
of Cu-O. With the carbon atom suspended in solution, CO2 ads*- is readily
protonated to form the HCOO- radical. And HCOO- as a product rapidly desorbs from
the copper surface with a second electron transfer to the adsorbed species.
PMID- 25844930
TI - Synthesis and pharmacology of halogenated delta-opioid-selective [d
Ala(2)]deltorphin II peptide analogues.
AB - Deltorphins are naturally occurring peptides produced by the skin of the giant
monkey frog (Phyllomedusa bicolor). They are delta-opioid receptor-selective
agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala
(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II
template, which is delta-selective in in vitro radioligand binding assays over
the MU- and kappa-opioid receptors. It is a full agonist in [(35)S]GTPgammaS
functional assays and analgesic when administered supraspinally to mice.
Analgesia of 3 (GATE3-8) is blocked by the selective delta receptor antagonist
naltrindole, indicating that the analgesic action of 3 is mediated by the delta
opioid receptor. We have established a radioligand in which (125)I is
incorporated into 3 (GATE3-8). The radioligand has a KD of 0.1 nM in Chinese
hamster ovary (CHO) cells expressing the delta receptor. Additionally, a series
of peptides based on 3 (GATE3-8) was synthesized by incorporating various
halogens in the para position on the aromatic ring of Phe(3). The peptides were
characterized for binding affinity at the MU-, delta-, and kappa-opioid
receptors, which showed a linear correlation between binding affinity and the
size of the halogen substituent. These peptides may be interesting tools for
probing delta-opioid receptor pharmacology.
PMID- 25844920
TI - Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular
Complexity.
PMID- 25844933
TI - Synthesis of alpha-amino acidato derivatives of niobium and tantalum pentahalides
and their conversion into iminium salts.
AB - Dinuclear complexes of formula Nb2Cl9[O2CCH(R)NR'R"2-kappaO,kappaO] (R =
CH2CHMe2, R' = R" = H, 1a; R = CH2Ph, R' = R" = H, 1b; R = CH2CH2SCH3, R' = R" =
H, 1c; R = R' = H, R" = Me, 1d; R = CH2Ph, R' = R" = Me, 1e;
Nb2Cl9[O2C?CH(CH2)3NH?], 1f) were prepared by allowing NbCl5 to react in
dichloromethane with the appropriate alpha-amino acid in 1:2 amino acid/Nb molar
ratio. The 1:1 reactions between MX5 (M = Nb, Ta; X = Cl, Br) and a series of
alpha-amino acids resulted in the formation of the iminium salts
[(R)CH?NR'R"2][MX6] (R = CH2Ph, R' = R" = Me: M = Nb, X = Cl, 2a; M = Nb, X = Br,
2b; M = Ta, X = Cl, 2c; M = Ta, X = Br, 2d; R = CH2Ph, R' = R" = H, M = Nb: X =
Cl, 3a; X = Br, 3b; R = CH2CHMe2, R' = R" = H, M = Nb, X = Cl, 4; R = R' = H, R"
= Me, M = Nb, X = Cl, 5). The formate/amino acidate derivative
NbCl3(O2CH)[O2CCH(CH2Ph)NMe2], 6, was isolated and identified as coproduct of the
1:1 reaction between NbCl5 and N,N-dimethyl-l-phenylalanine, leading to 2a. All
of the compounds were characterized by analytical and spectroscopic methods and
by X-ray diffractometry in the cases of 2a, 2b, and 2d. Moreover, density
functional theory studies were carried out to shed light on mechanistic and
structural aspects.
PMID- 25844932
TI - Rapid initiation of intravenous epoprostenol infusion is the favored option in
patients with advanced pulmonary arterial hypertension.
AB - BACKGROUND: Intravenous infusion (IVI) of epoprostenol is an effective treatment
for patients with advanced pulmonary arterial hypertension (PAH). However, there
is no widely accepted standard method for initiating the IVI therapy. This study
evaluated the hemodynamic improvements achieved with IVI epoprostenol to
determine the optimal protocol for treatment initiation. METHODS AND RESULTS: We
retrospectively analyzed 42 consecutive PAH patients who underwent IVI
epoprostenol in Keio University Hospital from 2001 to 2013. The study group
comprised 30 women with a mean age of 34.3 +/- 1.9 years. The etiology of PAH was
idiopathic or heritable PAH (I/HPAH) in 38 cases, PAH associated with connective
tissue disease in 3, and Eissenmenger's syndrome in the remaining case. We
divided the patients into rapid- and slow-initiation therapy groups according to
the cumulative epoprostenol dose administered during the first 180 days, and
compared the hemodynamic changes between the groups. The median cumulative doses
were 6142 +/- 165 MUg/kg and 3998 +/- 132 MUg/kg epoprostenol, respectively.
While there were no significant differences in mean pulmonary artery pressure
(mPAP), pulmonary vascular resistance (PVR), or cardiac index (CI) between the
groups before the IVI epoprostenol therapy, the rapid-initiation therapy group
achieved significant improvements in these hemodynamic data compared with the
slow-initiation therapy group (P < 0.005) at the follow-up right-heart
catheterization (RHC). CONCLUSION: Rapid initiation of IVI epoprostenol therapy
achieved the optimal hemodynamic improvements in patients with severe PAH.
PMID- 25844935
TI - Down Expression of FBP1 Is a Negative Prognostic Factor for Non-Small-Cell Lung
Cancer.
AB - Downregulation of fructose-1,6-bisphosphatse-1 (FBP1) was observed in several
cancers but its role in the lung cancer still remains unknown. We examined the
cancer tissues from 140 patients with nonsmall cell lung cancer patients and
found that the relative gene expression of FBP1 was significantly lower in lung
cancer tissues as compared to incisal marginal tissues and normal tissues. The
patients with higher level of FBP1 RNA expression have significantly longer
disease free survival and overall survival as compared to the lower expression
groups. There was a negative correlation with the level of FBP1 and recurrence of
the lung cancer.
PMID- 25844936
TI - Study of wetting on chemically soften interfaces by using combined solution
thermodynamics and DFT calculations: forecasting effective softening elements.
AB - Despite recent progress in understanding the wetting principles on soft solids,
the roles of chemical bonding in the formation of interfaces have been largely
ignored, because most of these studies are conducted at room temperatures. Here
we propose a universal wetting principle from solution thermodynamics to account
for the softening of both the solid and liquid surfaces (stable or metastable).
Density functional theory (DFT) calculations are applied to evaluate the
stability and electron transportation across the interfaces. We find that wetting
is dominated by the system entropy changes involving not only the stable liquid
alloy phase but also the metastable liquid oxide phases. The state-of-art
multicomponent solution thermodynamic models and databases are applied to
describe the entropy changes and predict the wetting behaviors. Our results show
that by chemically softening either the liquid or the solid phase, the wetting
angle reduces. And an effective soften agent/additive (either in the form of
chemical elements or molecules) will weaken the bonds within the liquid (or
solid) phase and promote new bonds at the interfaces, thus increasing the
interface entropy. Subsequently, as an example, Ti and Zr are proposed as
effective softening elements to improve the wetting of aluminum liquid on
B6Si(s). This approach provides a concept and tool to advance research in
catalytic chemistry, nucleation (growth), elastowetting, and cell-substrate
interactions.
PMID- 25844934
TI - Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza.
Results of the Flu Watch Cohort Study.
AB - RATIONALE: A high proportion of influenza infections are asymptomatic. Animal and
human challenge studies and observational studies suggest T cells protect against
disease among those infected, but the impact of T-cell immunity at the population
level is unknown. OBJECTIVES: To investigate whether naturally preexisting T-cell
responses targeting highly conserved internal influenza proteins could provide
cross-protective immunity against pandemic and seasonal influenza. METHODS: We
quantified influenza A(H3N2) virus-specific T cells in a population cohort during
seasonal and pandemic periods between 2006 and 2010. Follow-up included paired
serology, symptom reporting, and polymerase chain reaction (PCR) investigation of
symptomatic cases. MEASUREMENTS AND MAIN RESULTS: A total of 1,414 unvaccinated
individuals had baseline T-cell measurements (1,703 participant observation
sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and
strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking
antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera
(1,431 sets) showed 205 (14%) had evidence of infection based on fourfold
influenza antibody titer rises. The presence of NP-specific T cells before
exposure to virus correlated with less symptomatic, PCR-positive influenza A
(overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P =
0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection
was independent of baseline antibodies. Influenza-specific T-cell responses were
detected in 43%, indicating a substantial population impact. CONCLUSIONS:
Naturally occurring cross-protective T-cell immunity protects against symptomatic
PCR-confirmed disease in those with evidence of infection and helps to explain
why many infections do not cause symptoms. Vaccines stimulating T cells may
provide important cross-protective immunity.
PMID- 25844938
TI - Triboelectric charging sequence induced by surface functionalization as a method
to fabricate high performance triboelectric generators.
AB - Two different materials, apart from each other in a triboelectric series, are
required to fabricate high performance triboelectric generators (TEGs). Thus, it
often limits the choices of materials and causes related processing issues for
TEGs. To address this issue, we report a simple surface functionalization method
that can effectively change the triboelectric charging sequence of the materials,
broadening material choices and enhancing the performance of TEGs. Specifically,
we functionalized the surfaces of the polyethylene terephthalate (PET) films
either with poly-l-lysine solution or trichloro(1H,1H,2H,2H-perfluorooctyl)
silane (FOTS). Consequently, the PET surfaces were modified to have different
triboelectric polarities in a triboelectric series. The TEGs, fabricated using
this approach, demonstrated the maximum Vopen-circuit (Voc) of ~330 V and Jshort
circuit (Jsc) of ~270 mA/m(2), respectively, at an applied force of 0.5 MPa.
Furthermore, the functionalized surfaces of TEGs demonstrated superior stability
during cyclic measurement over 7200 cycles, maintaining the performance even
after a month. The approach introduced here is a simple, effective, and cost
competitive way to fabricate TEGs, which can also be easily adopted for various
surface patterns and device structures.
PMID- 25844937
TI - Use of formalin-fixed paraffin-embedded samples for gene expression studies in
breast cancer patients.
AB - To obtain gene expression profiles from samples collected in clinical trials, we
conducted a pilot study to assess feasibility and estimate sample attrition rates
when profiling formalin-fixed, paraffin-embedded specimens. Ten matched fresh
frozen and fixed breast cancer samples were profiled using the Illumina HT-12 and
Ref-8 chips, respectively. The profiles obtained with Ref 8, were neither
technically nor biologically reliable since they failed to yield the expected
separation between estrogen receptor positive and negative samples. With the use
of Affymetrix HG-U133 2.0 Plus chips on fixed samples and a quantitative
polymerase chain reaction -based sample pre-assessment step, results were
satisfactory in terms of biological reliability, despite the low number of
present calls (M = 21%+/-5). Compared with the Illumina DASL WG platform,
Affymetrix data showed a wider interquartile range (1.32 vs 0.57, P<2.2 E-16,)
and larger fold changes. The Affymetrix chips were used to run a pilot study on
60 fixed breast cancers. By including in the workflow the sample pre-assessment
steps, 96% of the samples predicted to give good results (44/46), were in fact
rated as satisfactory from the point of view of technical and biological
meaningfulness. Our gene expression profiles showed strong agreement with
immunohistochemistry data, were able to reproduce breast cancer molecular
subtypes, and allowed the validation of an estrogen receptor status classifier
derived in frozen samples. The approach is therefore suitable to profile formalin
fixed paraffin-embedded samples collected in clinical trials, provided that
quality controls are run both before (sample pre-assessment) and after
hybridization on the array.
PMID- 25844939
TI - Football fan aggression: the importance of low Basal cortisol and a fair referee.
AB - Fan aggression in football (soccer) is a societal problem that affects many
countries worldwide. However, to date, most studies use an epidemiological or
survey approach to explain football fan aggression. This study used a controlled
laboratory study to advance a model of predictors for fan aggression. To do so,
football fans (n = 74) saw a match summary in which their favorite team lost
against their most important rival. Next, we measured levels of aggression with
the hot sauce paradigm, in which fans were given the opportunity to administer a
sample of hot sauce that a rival football supporter had to consume. To
investigate if media exposure had the ability to reduce aggression, before the
match fans saw a video in which fans of the rival team commented in a neutral,
negative, or positive manner on their favorite team. Results showed that the
media exposure did not affect aggression. However, participants displayed high
levels of aggression and anger after having watched the match. Also, aggression
was higher in fans with lower basal cortisol levels, which suggests that part of
the aggression displayed was proactive and related to anti-social behavior.
Furthermore, aggression was higher when the referee was blamed and aggression was
lower when the performance of the participants' favorite team was blamed for the
match result. These results indicate that aggression increased when the match
result was perceived as unfair. Interventions that aim to reduce football fan
aggression should give special attention to the perceived fairness of the match
result.
PMID- 25844940
TI - Energy Thresholds of DNA Damage Induced by UV Radiation: An XPS Study.
AB - This work stresses on damage at the molecular level caused by ultraviolet
radiation (UV) in the range from 3.5 to 8 eV, deoxyribonucleic acid (DNA) films
observed by X-ray photoelectron spectroscopy (XPS). Detailed quantitative XPS
analysis, in which all the amounts are relative to sodium-assumed not to be
released from the samples, of the carbon, oxygen, and particularly, nitrogen
components, reveals that irradiation leads to sugar degradation with CO-based
compounds release for energies above 6.9 eV and decrease of nitrogen groups which
are not involved in hydrogen bonding at energies above 4.2 eV. Also the phosphate
groups are seen to decrease to energies above 4.2 eV. Analysis of XPS spectra
allowed to conclude that the damage on bases peripheral nitrogen atoms are
following the damage on phosphates. It suggests that very low kinetic energy
photoelectrons are ejected from the DNA bases, as a result of UV light induced
breaking of the phosphate ester groups which forms a transient anion with
resonance formation and whereby most of the nitrogen DNA peripheral groups are
removed. The degree of ionization of DNA was observed to increase with radiation
energy, indicating that the ionized phosphate groups are kept unchanged. This
result was interpreted by the shielding of phosphate groups caused by water
molecules hydration near sodium atoms.
PMID- 25844943
TI - Replacing the elderly with older adults in JGSW publications.
PMID- 25844941
TI - Behavioral Interventions to Reduce Sexual Risk Behavior in Adults with HIV/AIDS
Receiving HIV Care: A Systematic Review.
AB - Regular interactions with people living with HIV/AIDS (PLWHA) who are receiving
care provide caregivers opportunities to deliver interventions to reduce HIV
related risks. We conducted a systematic review of behavioral interventions for
PLWHA (provided at individual level by caregivers at HIV care settings) to
determine their efficacy in reducing sexual risk behavior. Conference websites
and biomedical literature databases were searched for studies from 1981 to 2013.
Randomized and quasi-randomized controlled trials (with standard-of-care control
groups), considering at least one of a list of HIV-related behavioral or
biological outcomes in PLWHA aged >=18 receiving HIV care with at least 3-month
follow-up were included. No language or publication status restrictions were set.
Standardized search, data abstraction, and evaluation methods were used. Five
randomized controlled trials were included in the review. We found limited
evidence that sexual risk reduction interventions increase condom use consistency
in HIV transmission risk acts, and reduce the number of (casual) sexual partners.
We still believe that regular interactions between HIV care providers and PLWHA
provide valuable opportunities for theory-based sexual risk reduction
interventions to restrain the spread of HIV.
PMID- 25844942
TI - IFI35, mir-99a and HCV genotype to predict sustained virological response to
pegylated-interferon plus ribavirin in chronic hepatitis C.
AB - Although, the treatment of chronic hepatitis C (CHC) greatly improved with the
use of direct antiviral agents, pegylated-interferon (PEG-IFN) plus ribavirin
remains an option for many patients, worldwide. The intra-hepatic level of
expression of interferon stimulated genes (ISGs) and the rs12979860 CC genotype
located within IFNL3 have been associated with sustained virological response
(SVR), in patients with CHC. The aim of the study was to identify micro-RNAs
associated with SVR and to build an accurate signature to predict SVR. Pre
treatment liver biopsies from 111 patients, treated with PEG-IFN plus ribavirin,
were studied. Fifty-seven patients had SVR, 36 non-response (NR) and 18 relapse
(RR). The expression of 851 human miRNAs and 30 selected mRNAs, including ISGs,
was assessed by RT-qPCR. In the first group of patients (screen), 20 miRNAs out
of the 851 studied were deregulated between NRs and SVRs. From the 4 miRNAs
validated (mir-23a, mir-181a*, mir-217 and mir-99a), in the second group of
patients (validation), 3 (mir-23a, mir-181a* and mir-99a) were down-regulated in
NRs as compared to SVRs. The ISGs, studied, were accumulated in SVRs and IFNL3
rs12979860 CT/TT carriers compared respectively to NRs and CC carriers.
Combining, clinical data together with the expression of selected genes and micro
RNAs, we identified a signature (IFI35, mir-99a and HCV genotype) to predict SVR
(AUC:0.876) with a positive predictive value of 86.54% with high sensibility
(80%) and specificity (80.4%). This signature may help to characterize patients
with low chance to respond to PEG-IFN/ribavirin and to elucidate mechanisms of
NR.
PMID- 25844944
TI - Induction and Repair of DNA DSB as Revealed by H2AX Phosphorylation Foci in Human
Fibroblasts Exposed to Low- and High-LET Radiation: Relationship with Early and
Delayed Reproductive Cell Death.
AB - The spatial distribution of radiation-induced DNA breaks within the cell nucleus
depends on radiation quality in terms of energy deposition pattern. It is
generally assumed that the higher the radiation linear energy transfer (LET), the
greater the DNA damage complexity. Using a combined experimental and theoretical
approach, we examined the phosphorylation-dephosphorylation kinetics of radiation
induced gamma-H2AX foci, size distribution and 3D focus morphology, and the
relationship between DNA damage and cellular end points (i.e., cell killing and
lethal mutations) after exposure to gamma rays, protons, carbon ions and alpha
particles. Our results showed that the maximum number of foci are reached 30 min
postirradiation for all radiation types. However, the number of foci after 0.5 Gy
of each radiation type was different with gamma rays, protons, carbon ions and
alpha particles inducing 12.64 +/- 0.25, 10.11 +/- 0.40, 8.84 +/- 0.56 and 4.80
+/- 0.35 foci, respectively, which indicated a clear influence of the track
structure and fluence on the numbers of foci induced after a dose of 0.5 Gy for
each radiation type. The gamma-H2AX foci persistence was also dependent on
radiation quality, i.e., the higher the LET, the longer the foci persisted in the
cell nucleus. The gamma-H2AX time course was compared with cell killing and
lethal mutation and the results highlighted a correlation between cellular end
points and the duration of gamma-H2AX foci persistence. A model was developed to
evaluate the probability that multiple DSBs reside in the same gamma-ray focus
and such probability was found to be negligible for doses lower than 1 Gy. Our
model provides evidence that the DSBs inside complex foci, such as those induced
by alpha particles, are not processed independently or with the same time
constant. The combination of experimental, theoretical and simulation data
supports the hypothesis of an interdependent processing of closely associated
DSBs, possibly associated with a diminished correct repair capability, which
affects cell killing and lethal mutation.
PMID- 25844945
TI - Analyses of ionizing radiation effects in vitro in peripheral blood lymphocytes
with Raman spectroscopy.
AB - The use of Raman spectroscopy to measure the biochemical profile of healthy and
diseased cells and tissues may be a potential solution to many diagnostic
problems in the clinic. Although extensively used to identify changes in the
biochemical profiles of cancerous cells and tissue, Raman spectroscopy has been
used less often for analyzing changes to the cellular environment by external
factors such as ionizing radiation. In tandem with this, the biological impact of
low doses of ionizing radiation remains poorly understood. Extensive studies have
been performed on the radiobiological effects associated with radiation doses
above 0.1 Gy, and are well characterized, but recent studies on low-dose
radiation exposure have revealed complex and highly variable responses. We report
here the novel finding that demonstrate the capability of Raman spectroscopy to
detect radiation-induced damage responses in isolated lymphocytes irradiated with
doses of 0.05 and 0.5 Gy. Lymphocytes were isolated from peripheral blood in a
cohort of volunteers, cultured ex vivo and then irradiated. Within 1 h after
irradiation spectral effects were observed with Raman microspectroscopy and
principal component analysis and linear discriminant analysis at both doses
relative to the sham-irradiated control (0 Gy). Cellular DNA damage was confirmed
using parallel gamma-H2AX fluorescence measurements on the extracted lymphocytes
per donor and per dose. DNA damage measurements exhibited interindividual
variability among both donors and dose, which matched that seen in the spectral
variability in the lymphocyte cohort. Further evidence of links between spectral
features and DNA damage was also observed, which may potentially allow
noninvasive insight into the DNA remodeling that occurs after exposure to
ionizing radiation.
PMID- 25844946
TI - Biodosimetry Based on gamma-H2AX Quantification and Cytogenetics after Partial-
and Total-Body Irradiation during Fractionated Radiotherapy.
AB - The aim of this current study was to quantitatively describe radiation-induced
DNA damage and its distribution in leukocytes of cancer patients after
fractionated partial- or total-body radiotherapy. Specifically, the impact of
exposed anatomic region and administered dose was investigated in breast and
prostate cancer patients receiving partial-body radiotherapy. DNA double-strand
breaks (DSBs) were quantified by gamma-H2AX immunostaining. The frequency of
unstable chromosomal aberrations in stimulated lymphocytes was also determined
and compared with the frequency of DNA DSBs in the same samples. The frequency of
radiation-induced DNA damage was converted into dose, using ex vivo generated
calibration curves, and was then compared with the administered physical dose.
This study showed that 0.5 h after partial-body radiotherapy the quantity of
radiation-induced gamma-H2AX foci increased linearly with the administered
equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1
day thereafter but proportionality to the equivalent whole-body dose was
maintained. Conversely, the frequency of radiation-induced cytogenetic damage
increased from 0.5 h to 1 day after the first partial-body exposure with a linear
dependence on the administered equivalent whole-body dose, for prostate cancer
patients only. Only gamma-H2AX foci assessment immediately after partial-body
radiotherapy was a reliable measure of the expected equivalent whole-body dose.
Local tumor doses could be approximated with both assays after one day. After
total-body radiotherapy satisfactory dose estimates were achieved with both
assays up to 8 h after exposure. In conclusion, the quantification of radiation
induced gamma-H2AX foci, but not cytogenetic damage in peripheral leukocytes was
a sensitive and rapid biodosimeter after acute heterogeneous irradiation of
partial body volumes that was able to primarily assess the absorbed equivalent
whole-body dose.
PMID- 25844947
TI - In memoriam: Arthur C. Upton (1923-2015).
PMID- 25844948
TI - Connecting radiation-induced bystander effects and senescence to improve
radiation response prediction.
AB - For the last two decades radiation-induced bystander effects (RIBEs) have
attracted significant attention due to their possible implications for
radiotherapy. However, despite extensive research, the molecular pathways
associated with RIBEs are still not completely known. In the current study we
investigated the role of senescence in the bystander response. Irradiated (2, 4,
6 and 8 Gy) human colorectal carcinoma cells (HCT116) with p53(+/+) (wild-type)
or p53(-/-) (knockout) gene were co-incubated with nonirradiated cells of the
same type. Clonogenic and senescence assays were used for both irradiated and co
incubated bystander cell populations. We also performed additional measurements
on the number of remaining cells after the whole co-incubation period. For
radiation doses larger than 2 Gy we observed much larger fractions of senescent
cells in p53-positive populations compared to their p53-negative counterparts
(15.81% vs. 3.63% in the irradiated population; 2.89% vs. 1.05% in the bystander
population; 8 Gy; P < 0.05). Statistically significant differences between cell
lines in the clonogenic cell surviving fraction were observed for doses higher
than 4 Gy (1.61% for p53(+/+) vs. 0.19% for p53(-/-) in irradiated population;
3.57% for +/+ vs. 50.39% for -/- in bystander population; 8 Gy; P < 0.05). Our
main finding was that the number of senescent cells in the irradiated population
correlated strongly with the clonogenic cell surviving fraction (R = -0.98, P <
0.001) and the number of senescent cells (R = 0.97, P < 0.001) in the bystander
population. We also extended the standard linear-quadratic radiation response
model by incorporating the influence of the signals released by the senescent
cells, which accurately described the radiation response in the bystander
population. Our findings suggest that radiation-induced senescence might be a key
player in RIBE, i.e., the strength of RIBE depends on the amount of radiation
induced senescence.
PMID- 25844949
TI - The development and manufacture of influenza vaccines.
AB - The development and manufacture of an Influenza vaccine is unlike any other
product in the Vaccine industry because of the need to change composition on a
yearly basis. The poor efficacy of Influenza vaccines over the past 2 y in the
Northern Hemisphere invites questions on how the vaccines are manufactured and
how change in vaccine composition is controlled. The opinion expressed in this
commentary is that the risk of not making the correct HA protein is increased by
the need to adapt the new seasonal virus for good propagation in embryonated
chicken eggs. This adaptation is required because not enough doses can be made in
time for the new 'flu season unless productivity is reasonable. This problem is
not necessarily solved by going to a cell culture host for virus propagation and
that may explain why this more advanced technology approach is not more widely
used. A vaccine based on hemagglutinin (HA) protein that does not involve
Influenza virus propagation (such as Flublok(r)) side steps this particular
problem. The exact HA sequence can be used as is in the virus. The technology can
be run at large scale, already at 2 * 21,000L in Japan, in contrast to eggs where
scale-up is by multiplication; the HA product is highly purified and made
consistently in the form of rosettes.
PMID- 25844950
TI - An Apparatus to Deliver Mannitol Powder for Bronchial Provocation in Children
Under Six Years Old.
AB - BACKGROUND: Currently bronchial provocation testing (BPT) using mannitol powder
cannot be performed in children under 6 years. A primary reason is it is
challenging for children at this age to generate a consistent inspiratory effort
to inhale mannitol efficiently from a dry powder inhaler. A prototype system,
which does not require any inhalation training from the pediatric subject, is
reported here. It uses an external source of compressed air to disperse mannitol
powder into a commercial holding chamber. Then the subject uses tidal breathing
to inhale the aerosol. METHOD: The setup consists of a commercially available
powder disperser and VolumaticTM holding chamber. Taguchi experimental design was
used to identify the effect of dispersion parameters (flow rate of compressed
air, time compressed air is applied, mass of powder, and the time between
dispersion and inhalation) on the fine particle dose (FPD). The prototype was
tested in vitro using a USP throat connected to a next generation impactor. The
aerosols from the holding chamber were drawn at 10 L/min. A scaling factor for
estimating the provoking dose to induce a 15% reduction in forced expiratory
volume in 1 second (FEV1) (PD15) was calculated using anatomical dimensions of
the human respiratory tract at various ages combined with known dosing values
from the adult BPT. RESULTS: Consistent and doubling FPDs were successfully
generated based on the Taguchi experimental design. The FPD was reliable over a
range of 0.8 (+/-0.09) mg to 14 (+/-0.94) mg. The calculated PD15 for children
aged 1-6 years ranged from 7.1-30 mg. The FPDs generated from the proposed set up
are lower than the calculated PD15 and therefore are not expected to cause sudden
bronchoconstriction. CONCLUSION: A prototype aerosol delivery system has been
developed that is consistently able to deliver doubling doses suitable for
bronchial provocation testing in young children.
PMID- 25844951
TI - Risk Factors for Abdominal Incision Infection after Colorectal Surgery in a Saudi
Arabian Population: The Method of Surveillance Matters.
AB - BACKGROUND: Reported surgical site infection rates range from 2.1% to 40% after
colorectal surgery and are believed to be underestimated depending on the method
of surveillance. The study aims were to identify an accurate incidence and
associated risk factors for abdominal incision surgical site infection after
elective open colorectal surgery in a Saudi population. METHODS: This was a
prospective observational longitudinal study of 300 consecutive adult patients,
recruited upon admission to an 800-bed tertiary referral center. All consenting
adults admitted for elective open colorectal surgery were included. Patients were
followed for 36 d post-surgery by two certified and experienced wound care
experts who diagnosed abdominal incision surgical site infections. The definition
provided by the U.S. Centers for Disease Control and Prevention was used.
Statistical analysis was performed using both univariate and multivariable
logistic regression. RESULTS: Data were analyzed for 296 patients; the incidence
of abdominal surgical site infection was 30%. Factors associated with surgical
site infection by univariate analysis were pre-operative pre-albumin (p=0.04,
odds ratio [OR] 0.81, 95% confidence interval [CI] 0.66-0.99); operative
difficulty because of truncal obesity (p=0.006, OR 2.19, 95% CI 1.25-3.84) and
obesity measured by body mass index (p=0.002, OR 4.00, 95% CI 1.95-8.20).
Multivariable analysis identified only two significant risk factors: Pre
operative pre-albumin (p=0.02, OR 0.76, 95% CI 0.60-0.96), and obesity measured
by body mass index (BMI; p=0.001, OR 4.71, 95% CI 2.20-10.10). CONCLUSION:
Obesity and nutritional status correlated with post-operative abdominal surgical
site infection. The method of surveillance and length of follow-up impact the
rate reported.
PMID- 25844952
TI - Differentiation Between the Potential Subdural Space and Subarachnoid Space Was
Difficult With Fluoroscopy Due to Obesity.
PMID- 25844953
TI - Dexmedetomidine Attenuates Neurotoxicity Induced by Prenatal Propofol Exposure.
AB - BACKGROUND: Anesthetic agents (eg, isoflurane, propofol) may cause
neurodegeneration in the developing brains and impair animals' learning ability.
Dexmedetomidine (DEX), a selective alpha 2-adrenoreceptor agonist, has
antiapoptotic properties in several brain injury models. Here, we tested whether
DEX can protect the brain from neurodegeneration in rats exposed to propofol in
utero. MATERIALS AND METHODS: Fetal rats of embryonic day 20 were exposed in
utero for 1 hour to propofol anesthesia with DEX or saline, or no anesthesia
(control). The fetal brains were harvested 6 hours later. Cleaved caspase-3
levels and the relative number of ionized calcium-binding adaptor molecule 1
(IBA1)-positive cells were assessed by Western blot and immunohistochemistry.
Learning and memory functions of the offspring in a separate cohort were assessed
at postnatal day 35 by using an 8-arm radial maze. RESULTS: Propofol anesthesia
in pregnant rats augmented caspase-3 activation by 217% in the brain tissues of
fetal rats and increased the number of IBA1-positive cells in the cortex by 40%
and in the thalamus by 270%. Juvenile rats exposed prenatally to propofol were
not different than controls on spontaneous locomotor activity, but made more
errors of omission and took longer to complete visiting all 8 arms on days 1, 2,
and 3 across a 5-day test in the radial arm maze. This neurocognitive deficit was
prevented by administration of DEX (5.0 ug/kg, IP), which also significantly
inhibited propofol-induced caspase-3 activation and microglial response in the
fetal brains. CONCLUSIONS: DEX attenuates neuronal injury induced by maternal
propofol anesthesia in the fetal brains, providing neurocognitive protection in
the offspring rats.
PMID- 25844954
TI - A Case of Nephrogenic Diabetes Insipidus During Transsphenoidal Pituitary
Adenomectomy.
PMID- 25844955
TI - A Universal Aptamer Chimera for the Delivery of Functional microRNA-126.
AB - microRNAs (miRs) regulate vascular diseases such as atherosclerosis and cancer.
miR-126 is important for endothelial cell signaling and promotes angiogenesis,
protects against atherosclerosis, and reduces breast cancer cell growth and
metastasis. The overexpression of miR-126, therefore, may be an attractive
therapeutic strategy for the treatment of cardiovascular disease or cancer. Here
we report a novel strategy to deliver miR-126 to endothelial and breast cancer
cells. We tested three different strategies to deliver miR-126 by linking the miR
to an aptamer for the ubiquitously expressed transferrin receptor (transferrin
receptor aptamer, TRA). Linking the precursor of miR-126 (pre-miR-126) to the TRA
by annealing of a complementary stick led to efficient uptake and processing of
miR-126, resulting in the delivery of 1.6*10(6)+/-0.3*10(6) copies miR-126-3p per
ng RNA in human endothelial cells and 7.4*10(5)+/-2*10(5) copies miR-126-3p per
ng in MCF7 breast cancer cells. The functionality of the active TRA-miR-126
chimera was further demonstrated by showing that the chimera represses the known
miR-126 target VCAM-1 and improved endothelial cell sprouting in a spheroid
assay. Moreover, the TRA-miR-126 chimera reduced proliferation and paracrine
endothelial cell recruitment of breast cancer cells to a similar extent as miR
126-3p mimics introduced by conventional liposome-based transfection. Together,
this data demonstrates that pre-miR-126 can be delivered by a non-specific
aptamer to exert biological functions in two different cell models. The use of
the TRA-miR-126 chimera or the combination of the delivery strategy with other
endothelial or tumor specific aptamers may provide an interesting therapeutic
option to treat vascular disease or cancers.
PMID- 25844957
TI - Mechanical Strain Induced Tunable Anisotropic Wetting on Buckled PDMS Silver
Nanorods Arrays.
AB - We report the fabrication of anisotropic superhydrophobic surface with dual-scale
roughness by the deposition of silver nanorods arrays on prestretched
poly(dimethylsiloxane) (PDMS) using oblique angle deposition and subsequent
release of strain after the deposition, which resulted in the formation of
microbuckles/wrinkles. The amplitude and periodicity of the wrinkles were tuned
by varying the prestretching mechanical strain (epsilon) applied to the PDMS film
from 0 to 30% prior to Ag nanorods deposition. The peaks and valleys in the
surface topography of Ag nanorods arrays covered PDMS films lead to anisotropic
wetting by water droplet. The droplet is free to move along the direction
parallel to the wrinkles, but the droplet moving perpendicular to the wrinkles
confront energy barrier leading to wetting anisotropy. The anisotropic
wettability was tuned from 22 to 37 degrees for 10-30% prestretched PDMS film.
The dual scale roughness (nanorods on micro wrinkles) was found to be responsible
for the superhydrophobicity (contact angle ~155 degrees ) of the sample prepared
for 30% prestretched PDMS film in perpendicular direction. The wetting behavior
of the Ag nanorods PDMS film surface was reversibly tuned by applying the
mechanical strain, which induces the change in the microscale roughness
determined by amplitude (A) and periodicity (lambda) of the buckles. Most
interestingly, the water droplet also displayed the anisotropy in the roll-off
angle. The effect of different A and lambda on anisotropic wettability of Ag
nanorods arrays/PDMS film was also demonstrated by lattice Boltzmann (LB)
modeling. These findings may produce a promising way of controlling the direction
of liquid flow such as in microfluidic devices and transportation of the
microliter water droplets in a preset direction.
PMID- 25844958
TI - Presentation and progression of childhood-onset inflammatory bowel disease in
Northern Stockholm County.
AB - BACKGROUND: Some studies have suggested that childhood-onset inflammatory bowel
disease (IBD) is characterized by extensive intestinal involvement and rapid
progression to complications. Here, we report the presentation and progression of
patients diagnosed with IBD during childhood in a population-based cohort from
northern Stockholm County. METHODS: Medical records for all 280 patients
diagnosed in the period 1990-2007 with childhood-onset IBD in northern Stockholm
County were followed until 2011 (median follow-up time, 8.8 yr). Disease
phenotypes were classified according to the Paris pediatric IBD classification.
RESULTS: Among the 74 patients with ulcerative colitis, 72% presented with
pancolitis. Among the 200 patients with Crohn's disease (CD), 75% presented with
colitis. Complicated disease behavior was observed in 18% of patients with CD by
end of follow-up. Extension of the disease territory was observed in 22% of
patients with ulcerative colitis and 15% of patients with CD. The cumulative risk
of intra-abdominal surgery after 10 years was 8% (95% confidence interval, 4%
20%) for ulcerative colitis and 22% (95% confidence interval, 15%-28%) for
patients with CD. Nonmucosal healing at 1 year was associated with a complicated
disease course in patients with CD (hazard ratio = 14.56; 95% confidence
interval, 1.79-118.68; P = 0.01). CONCLUSIONS: Patients with childhood-onset IBD
were characterized by extensive colitis that was relatively stable over time and
associated with a relatively low risk of complications and abdominal surgery. Our
findings confirm the more extensive disease location in pediatric IBD but did not
identify the proposed dynamic and aggressive nature of the childhood-onset
phenotype. The association of nonmucosal healing with a complicated disease
course suggests that endoscopy should guide treatment intensity in childhood
onset CD.
PMID- 25844960
TI - MicroRNAs in inflammatory bowel diseases: paradoxes and possibilities.
AB - MicroRNAs (miRNAs) are single-stranded RNA molecules, which influence the
translation of messenger RNA and hence protein synthesis. The altered expression
of miRNAs in disease states in cancer and autoimmune diseases including
inflammatory bowel disease is providing new insights into disease pathogenesis.
This understanding is leading to consideration of the utility of miRNAs in
diagnostics, prognostics, and therapeutics in inflammatory bowel disease. A
literature search was conducted using the MEDLINE/PubMed databases using search
terms inflammatory bowel disease, miRNA, treatment, and biomarkers.
PMID- 25844959
TI - Recent advances in characterizing the gastrointestinal microbiome in Crohn's
disease: a systematic review.
AB - BACKGROUND: The intestinal microbiota is involved in the pathogenesis of
inflammatory bowel disease. A reduction in the diversity of the intestinal
microbiota as well as specific taxonomic and functional shifts have been reported
in Crohn's disease and may play a central role in the inflammatory process. The
aim was to systematically review recent developments in the structural and
functional changes observed in the gastrointestinal microbiome in patients with
Crohn's Disease. RESULTS: Seventy-two abstracts were included in this review. The
effects of host genetics, disease phenotype, and inflammatory bowel disease
treatment on the gastrointestinal microbiome in Crohn's disease were reviewed,
and taxonomic shifts in patients with early and established disease were
described. The relative abundance of Bacteroidetes is increased and Firmicutes
decreased in Crohn's disease compared with healthy controls. Enterobacteriaceae,
specifically Eschericia coli, is enriched in Crohn's disease. Faecalibacterium
prausnitzii is found at lower abundance in Crohn's disease and in those with
postoperative recurrence. Observed functional changes include major shifts in
oxidative stress pathways, a decrease in butanoate and propanoate metabolism gene
expression, lower levels of butyrate, and other short-chain fatty acids,
decreased carbohydrate metabolism, and decreased amino acid biosynthesis.
CONCLUSIONS: Changes in microbial composition and function have been described,
although a causative role remains to be established. Larger, prospective, and
longitudinal studies are required with deep interrogation of the microbiome if
causality is to be determined, and refined microbial manipulation is to emerge as
a focused therapy.
PMID- 25844961
TI - Endogenous levels of circulating androgens and risk of Crohn's disease and
ulcerative colitis among women: a nested case-control study from the nurses'
health study cohorts.
AB - BACKGROUND: Androgens, which are known to be altered by exogenous hormone use,
have recently been linked to alterations of the gut microbiome and mucosal immune
function. No study has evaluated the association between circulating levels of
androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS:
We conducted a nested case-control study of women enrolled in the Nurses' Health
Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and
UC were each matched to 2 controls. Prediagnosis plasma levels of
dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin
were measured. We examined the association of each analyte with risk of CD or UC
using conditional logistic regression models. RESULTS: Compared with women in the
lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD
were 0.86 (95% confidence interval, 0.39-1.90) for women in the second quintile,
0.49 (95% confidence interval, 0.21-1.15) for the third quartile, 0.22 (0.08
0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16-0.99) for
the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a
consistent association between prediagnostic testosterone and risk of UC (Plinear
trend = 0.84). We also did not observe any association between plasma levels of
sex hormone-binding globulin or dehydroepiandrosterone sulfate and risk of UC or
CD (all Plinear trends > 0.10). CONCLUSIONS: Among women, prediagnostic
circulating testosterone is associated with a lower risk of CD but not UC.
Further studies to understand the biological mechanisms by which endogenous
androgens may mediate the etiopathogenesis of CD are warranted.
PMID- 25844962
TI - Iron Replacement in Patients with Inflammatory Bowel Disease: A Systematic Review
and Meta-analysis.
AB - BACKGROUND: A number of controlled trials and prospective studies have compared
intravenous (IV) to oral (PO) iron for the treatment of iron deficiency anemia
with mixed results. METHODS: We conducted a systematic review of trials published
on 2014 that compared IV with PO iron to treat in patients with IBD. Meta
analysis was performed to generate effect estimates. Quality assessment was also
performed according to GRADE criteria. RESULTS: Five studies met our inclusion
criteria, enrolling 694 patients. For the primary outcome of "response"
(hemoglobin rise >2 g/dL), there was no significant difference between IV or PO
iron; risk ratio for response with IV was 1.08 (95% CI, 0.9-1.2; P = 0.2). For
the secondary outcome of mean change in hemoglobin (g/dL), the mean difference
between PO and IV iron was not statistically significant (mean difference, 0.6
g/dL, 96% CI, -0.1 to 1.3; P = 0.08). IV iron was associated with a significantly
greater initial rise in serum ferritin compared with PO iron (mean difference 89
ng/mL; 95% CI, 29-148, P = 0.003). There was a lower risk of withdrawal due to
adverse events in these trials in the IV iron cohorts when compared with PO iron
(risk ratio, 0.4; 95% CI, 0.1-1.0; P = 0.05). CONCLUSIONS: We found no
significant difference between IV and PO iron in correcting iron-deficiency
anemia in patients with IBD in this meta-analysis. Patients who received IV iron
had a greater rise in serum ferritin and were less likely to stop treatment due
to adverse events, when compared with those who received PO iron.
PMID- 25844963
TI - Vedolizumab for induction and maintenance of remission in ulcerative colitis: a
Cochrane systematic review and meta-analysis.
AB - BACKGROUND: We performed a systematic review to evaluate the efficacy and safety
of vedolizumab for induction and maintenance of remission in ulcerative colitis.
METHODS: A literature search to June 2014 identified all applicable randomized
trials. Outcome measures were clinical and endoscopic remission, clinical and
endoscopic response, quality of life, and adverse events. The risk ratio (RR) and
95% confidence intervals (CI) were estimated for each outcome. Study quality was
evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to
assess the quality of the evidence. MAIN RESULTS: Four studies (606 patients)
were included. The risk of bias was low. Pooled analyses indicated that
vedolizumab was significantly superior to placebo for induction of remission (RR
= 0.86, 95% CI, 0.80-0.91), clinical response (RR = 0.82, 95% CI, 0.75-0.91),
endoscopic remission (RR = 0.82, 95% CI, 0.75-0.91), and for achieving remission
at 52 weeks in week 6 responders (RR = 2.73, 95% CI, 1.78-4.18). GRADE analyses
suggested that the overall quality of the evidence was high for induction of
remission and moderate for maintenance therapy (due to sparse data consisting of
246 events). No statistically significant difference was observed in the
incidence of adverse events between vedolizumab and placebo. CONCLUSIONS:
Vedolizumab is superior to placebo as induction and maintenance therapy for
ulcerative colitis. Future studies are needed to define long-term efficacy and
safety of this agent.
PMID- 25844964
TI - gamma-Tocotrienol-induced endoplasmic reticulum stress and autophagy act
concurrently to promote breast cancer cell death.
AB - The anticancer effects of gamma-tocotrienol are associated with the induction of
autophagy and endoplasmic reticulum (ER) stress-mediated apoptosis, but a direct
relationship between these events has not been established. Treatment with 40
MUmol/L of gamma-tocotrienol caused a time-dependent decrease in cancer cell
viability that corresponds to a concurrent increase in autophagic and endoplasmic
reticulum (ER) stress markers in MCF-7 and MDA-MB-231 human breast cancer cells.
gamma-Tocotrienol treatment was found to cause a time-dependent increase in early
phase (Beclin-1, LC3B-II) and late phase (LAMP-1 and cathepsin-D) autophagy
markers, and pretreatment with autophagy inhibitors Beclin-1 siRNA, 3-MA or Baf1
blocked these effects. Furthermore, blockage of gamma-tocotrienol-induced
autophagy with Beclin-1 siRNA, 3-MA, or Baf1 induced a modest, but significant,
reduction in gamma-tocotrienol-induced cytotoxicity. gamma-Tocotrienol treatment
was also found to cause a decrease in mitogenic Erk1/2 signaling, an increase in
stress-dependent p38 and JNK1/2 signaling, as well as an increase in ER stress
apoptotic markers, including phospho-PERK, phospho-eIF2alpha, Bip, IRE1alpha, ATF
4, CHOP, and TRB3. In summary, these finding demonstrate that gamma-tocotrienol
induced ER stress and autophagy occur concurrently, and together act to promote
human breast cancer cell death.
PMID- 25844965
TI - Synovial heterogeneity in rheumatoid arthritis: the key for rational patient
stratification?
PMID- 25844966
TI - Balancing the benefits and risks of low-dose glucocorticoid in rheumatoid
arthritis.
AB - Glucocorticoids have potent anti-inflammatory and immunomodulatory effects and
are widely use in the management of rheumatoid arthritis in combination with
other synthetic and with biological disease-modifying anti-rheumatic drugs.
Concerns about the risk of adverse effects of glucocorticoids, especially if they
are given at higher dosages and for a longer time, hamper their use despite the
clear symptomatic and disease modifying benefits. However, the evidence base for
these concerns for low dose glucocorticoid therapy is quite limited due to the
scarcity of quality literature on its safety in rheumatoid arthritis. This review
discusses the current understanding about their disease-modifying effects,
toxicity data from recent trials and observational studies, recommendations for
their management and the current efforts to improve the therapeutic ratio of
glucocorticoid through the development of new formulations, such as modified
release prednisone.
PMID- 25844967
TI - Depressive symptoms are independently associated with pain perception in
Colombians with rheumatoid arthritis.
AB - AIMS: To examine the relationships between psychosocial factors and reported pain
in Colombians with Rheumatoid Arthritis (RA). METHODS: One hundred and three RA
patients [85% from the lowest socio-economic strata (SES) in the country]
recruited from outpatient centers in Neiva, Colombia were administered the
Disease Activity Scale (DAS) , which included a Visual Analog Scale (VAS)
arthritis pain/activity rating, Zung Depression Scale, State-Trait Anxiety
Inventory (STAI), Interpersonal Support Evaluation List-12 (ISEL-12), and Symptom
Checklist-90 Revised (SCL-90R). MAJOR RESULTS: VAS pain was not associated with
socio-demographic or medical factors, but was negatively associated with ISEL
tangible subscale (r=-0.22, p< 0.01; r=0.28, p<0.01). VAS pain was positively
associated with Zung Depression Scale score (r=0.38, p<0.001), STAI-State and
STAI-Trait Anxiety (r=0.23 and r=0.25 respectively, p's<0.01), SCL-90R Global
Severity Index (GSI) and Positive Symptom Total (PST) (r=0.23, p<0.05 and r=0.29,
p<0.01 respectively), and SCL-90R Somatization, Depression, and Anxiety subscales
(r=0.30, p< 0.01; r=0.28, p<0.01; and r=0.20, p<0.05 respectively). A linear
regression model showed that socio-demographic characteristics theoretically
associated with pain perception (gender, age, and SES) explained only 2.4% of the
variance of VAS scores (R(2)=0.02, p=0.49). The full model, including
psychosocial factors significantly associated with VAS scores explained 18.9% of
the variance in VAS pain perception scores (R(2)=0.19, p=0.02). The Zung
Depression Scale score was the only factor independently associated with VAS
pain, such that higher depression scores were associated with higher VAS ratings
(beta =0.13, p<0.01), controlling for gender, age, SES, STAI-State, STAI-Trait,
ISEL tangible, SCL-90R GSI, and SCL-90R PST. CONCLUSIONS: Depressive symptoms,
anxiety, social support, and psychopathological symptom distress were associated
with pain ratings, but only depressive symptoms were found to be uniquely
associated with higher pain perception, taking into account socio-demographic
characteristics and other psychosocial factors. Findings provide evidence for the
need to assess and treat pain in RA in Colombia from a bio-psycho-social
perspective. Future research is needed to determine effective depression
screening and evidence-based interventions for depressive symptoms in RA patients
in this socio-cultural context, as intervening in depression may decrease pain
perception.
PMID- 25844968
TI - Impact of bariatric surgery on life expectancy in severely obese patients with
diabetes: a decision analysis.
AB - OBJECTIVE: To create a decision analytic model to estimate the balance between
treatment risks and benefits for severely obese patients with diabetes.
BACKGROUND: Bariatric surgery leads to many desirable metabolic changes, but long
term impact of bariatric surgery on life expectancy in patients with diabetes has
not yet been quantified. METHODS: We developed a Markov state transition model
with multiple Cox proportional hazards models and logistic regression models as
inputs to compare bariatric surgery versus no surgical treatment for severely
obese diabetic patients. The model is informed by data from 3 large cohorts: (1)
159,000 severely obese diabetic patients (4185 had bariatric surgery) from 3 HMO
Research Network sites; (2) 23,000 subjects from the Nationwide Inpatient Sample;
and (3) 18,000 subjects from the National Health Interview Survey linked to the
National Death Index. RESULTS: In our main analyses, we found that a 45-year-old
woman with diabetes and a body mass index (BMI) of 45 kg/m gained an additional
6.7 years of life expectancy with bariatric surgery (38.4 years with surgery vs
31.7 years without surgery). Sensitivity analyses revealed that the gain in life
expectancy decreased with increasing BMI, until a BMI of 62 kg/m is reached, at
which point nonsurgical treatment was associated with greater life expectancy.
Similar results were seen for both men and women in all age groups. CONCLUSIONS:
For most severely obese patients with diabetes, bariatric surgery seems to
improve life expectancy; however, surgery may reduce life expectancy for the
super obese with BMIs over 62 kg/m.
PMID- 25844969
TI - Reliability of surgeon-specific reporting of complications after colectomy.
AB - OBJECTIVE: We sought to determine the reliability of surgeon-specific
postoperative complication rates after colectomy. BACKGROUND: Conventional
measures of surgeon-specific performance fail to acknowledge variation attributed
to statistical noise, risking unreliable assessment of quality. METHODS: We
examined all patients who underwent segmental colectomy with anastomosis from
2008 through 2010 participating in the Michigan Surgical Quality Collaborative
Colectomy Project. Surgeon-specific complication rates were risk-adjusted
according to patient characteristics with multiple logistic regression.
Hierarchical modeling techniques were used to determine the reliability of
surgeon-specific risk-adjusted complication rates. We then adjusted these rates
for reliability. To evaluate the extent to which surgeon-level variation was
reduced, surgeons were placed into quartiles based on performance and
complication rates were compared before and after reliability adjustment.
RESULTS: A total of 5033 patients (n = 345 surgeons) undergoing partial colectomy
reported a risk-adjusted complication rate of 24.5%. Approximately 86% of the
variability of complication rates across surgeons was explained by measurement
noise, whereas the remaining 14% represented true signal. Risk-adjusted
complication rates varied from 0% to 55.1% across quartiles before adjusting for
reliability. Reliability adjustment greatly diminished this variation, generating
a 1.2-fold difference (21.4%-25.6%). A caseload of 168 colectomies across 3 years
was required to achieve a reliability of more than 0.7, which is considered a
proficient level. Only 1 surgeon surpassed this volume threshold. CONCLUSIONS:
The vast majority of surgeons do not perform enough colectomies to generate a
reliable surgeon-specific complication rate. Risk-adjusted complication rates
should be viewed with caution when evaluating surgeons with low operative volume,
as statistical noise is a large determinant in estimating their surgeon-specific
complication rates.
PMID- 25844970
TI - Robotic-assisted transanal total mesorectal excision: the key against the
Achilles' heel of rectal cancer?
PMID- 25844971
TI - Reply to letter: "meta-analyses, from GIGO to PRISMA".
PMID- 25844972
TI - Reply to letter: "a systematic review of economic evaluations of enhanced
recovery pathways for colorectal surgery".
PMID- 25844974
TI - Emotional inertia and external events: The roles of exposure, reactivity, and
recovery.
AB - Increased moment-to-moment predictability, or inertia, of negative affect has
been identified as an important dynamic marker of psychological maladjustment,
and increased vulnerability to depression in particular. However, little is known
about the processes underlying emotional inertia. The current article examines
how the emotional context, and people's responses to it, are related to emotional
inertia. We investigated how individual differences in the inertia of negative
affect (NA) are related to individual differences in exposure, reactivity, and
recovery from emotional events, in daily life (assessed using experience
sampling) as well as in the lab (assessed using an emotional film-clip task),
among 200 participants commencing their first year of tertiary education. This
dual-method approach allowed us to assess affective responding on different
timescales, and in response to standardized as well as idiographic emotional
stimuli. Our most consistent finding, across both methods, was that heightened NA
inertia is related to decreased NA recovery following negative stimuli,
suggesting that higher levels of inertia may be mostly driven by impairments in
affect repair following negative events.
PMID- 25844973
TI - Emotional clarity as a function of neuroticism and major depressive disorder.
AB - Investigators have begun to document links between emotional clarity and forms of
negative emotionality, including neuroticism and major depressive disorder (MDD).
Researchers to date have relied almost exclusively on global self-reports of
emotional clarity; moreover, no studies have examined emotional clarity as a
function of valence, although this may prove to be crucial in understanding the
relation of emotional clarity to maladjustment. In 2 studies, we used experience
sampling methodology and multilevel modeling to examine the associations between
emotional clarity and 2 constructs that have been linked theoretically with
emotional clarity: neuroticism and depression. In Study 1 we assessed 95 college
students who completed a self-report measure of neuroticism. In Study 2 we
examined 53 adults diagnosed with MDD and 53 healthy adults. Reaction times to
negative and positive emotion ratings during the experience-sampling protocols
were used as an indirect measure of emotional clarity. Neuroticism was related to
lower clarity of negative, but not of positive, emotion. Similarly, compared with
the healthy controls, individuals with MDD had lower clarity of negative, but not
of positive, emotion. It is important to note, findings from both studies held
after controlling for baseline RTs and current levels of negative and positive
emotion. These findings highlight the importance of assessing valence when
examining emotional clarity and increase our understanding of the nature of the
emotional disturbances that characterize neuroticism and MDD.
PMID- 25844975
TI - Jealousy increased by induced relative left frontal cortical activity.
AB - Asymmetric frontal cortical activity may be one key to the process linking social
exclusion to jealous feelings. The current research examined the causal role of
asymmetric frontal brain activity in modulating jealousy in response to social
exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex
to manipulate asymmetric frontal cortical activity was combined with a modified
version of the Cyberball paradigm designed to induce jealousy. After receiving 15
min of tDCS, participants were excluded by a desired partner and reported how
jealous they felt. Among individuals who were excluded, tDCS to increase relative
left frontal cortical activity caused greater levels of self-reported jealousy
compared to tDCS to increase relative right frontal cortical activity or sham
stimulation. Limitations concerning the specificity of this effect and
implications for the role of the asymmetric prefrontal cortical activity in
motivated behaviors are discussed.
PMID- 25844976
TI - Statistical evaluation and modeling of cheap substrate-based cultivation medium
of Chlorella vulgaris to enhance microalgae lipid as new potential feedstock for
biolubricant.
AB - Chlorella vulgaris (C. vulgaris) microalga was investigated as a new potential
feedstock for the production of biodegradable lubricant. In order to enhance
microalgae lipid for biolubricant production, mixotrophic growth of C. vulgaris
was optimized using statistical analysis of Plackett-Burman (P-B) and response
surface methodology (RSM). A cheap substrate-based medium of molasses and corn
steep liquor (CSL) was used instead of expensive mineral salts to reduce the
total cost of microalgae production. The effects of molasses and CSL
concentration (cheap substrates) and light intensity on the growth of microalgae
and their lipid content were analyzed and modeled. Designed models by RSM showed
good compatibility with a 95% confidence level when compared to the cultivation
system. According to the models, optimal cultivation conditions were obtained
with biomass productivity of 0.123 g L(-1) day(-1) and lipid dry weight of 0.64 g
L(-1) as 35% of dry weight of C. vulgaris. The extracted microalgae lipid
presented useful fatty acid for biolubricant production with viscosities of 42.00
cSt at 40 degrees C and 8.500 cSt at 100 degrees C, viscosity index of 185, flash
point of 185 degrees C, and pour point of -6 degrees C. These properties showed
that microalgae lipid could be used as potential feedstock for biolubricant
production.
PMID- 25844977
TI - Expert opinion: How and when to perform CT myocardial perfusion imaging.
PMID- 25844978
TI - Comparison of Digital Tomosynthesis and Chest Radiography for the Detection of
Noncalcified Pulmonary and Hilar Lesions.
AB - OBJECTIVES: The aim of this study was to compare the sensitivity and specificity
of chest digital tomosynthesis (DTS) with chest radiography (CXR) for the
detection of noncalcified pulmonary nodules and hilar lesions using computed
tomography (CT) as the reference standard. MATERIALS AND METHODS: A total of 78
patients with suspected noncalcified pulmonary lesions on CXR were included in
the study. Two radiologists, blinded to the history and CT, analyzed the CXR and
the DTS images (separately), whereas a third radiologist analyzed the CXR and DTS
images together. Noncalcified intrapulmonary nodules and hilar lesions were
recorded for analysis. The interobserver agreement for CXR and DTS was assessed,
and the time taken to report the images was recorded. RESULTS: A total of 202
lesions were recorded in 78 patients. There were 111 true lesions confirmed on CT
in 53 patients; in 25 patients subsequent CT excluded a lesion. The overall
sensitivity was 32% for CXR and 49% for DTS. This improved to 54% when the
posteroanterior CXR and DTS were reviewed together (CXR-DTS). The overall
specificities for CXR, DTS, and CXR-DTS were 49%, 96%, and 98%, respectively.
There were 56 suspected hilar lesions with subgroup sensitivities of 76% for CXR,
65% for DTS, and 76% for CXR-DTS. The specificity for hilar lesions was 59%, 92%,
and 97% for CXR, DTS, and CXR-DTS, respectively. CONCLUSIONS: DTS significantly
improves the detectability of noncalcified nodules when compared with and when
used in combination with CXR. The specificity and interobserver agreement of DTS
in the diagnosis of suspected noncalcified pulmonary nodules and hilar lesions
are significantly better than those of CXR and approaches those of CT.
PMID- 25844979
TI - Signs in cardiopulmonary imaging: luftsichel sign.
PMID- 25844980
TI - Nutritional and other types of oedema, albumin, complex carbohydrates and the
interstitium - a response to Malcolm Coulthard's hypothesis: Oedema in
kwashiorkor is caused by hypo-albuminaemia.
AB - The various types of oedema in man are considered in relation to Starling's
hypothesis of fluid movement from capillaries, with the main emphasis on
nutritional oedema and the nephrotic syndrome in children. It is concluded that
each condition has sufficient anomalous findings to render Starling's hypothesis
untenable. The finding that the endothelial glycocalyx is key to control of fluid
movement from and into the capillaries calls for complete revision of our
understanding of oedema formation. The factors so far known to affect the
function of the glycocalyx are reviewed. As these depend upon sulphated
proteoglycans and other glycosaminoglycans, the argument is advanced that the
same abnormalities will extend to the interstitial space and that kwashiorkor is
fundamentally related to a defect in sulphur metabolism which can explain all the
clinical features of the condition, including the formation of oedema.
PMID- 25844981
TI - Refining the closed loop in the data age: research-to-practice transitions in
diabetes technology.
PMID- 25844982
TI - Factors that affect job satisfaction and intention to leave of allied health
professionals in a metropolitan hospital.
AB - OBJECTIVE: The purpose of the present study was to determine the aspects of the
allied health professional's job that contribute most to job satisfaction and
intention to leave in a metropolitan hospital. METHOD: Data were collected via a
questionnaire that was emailed to all clinical allied health staff at
Campbelltown and Camden Hospitals in New South Wales, Australia. The participants
then rated their level of satisfaction with various job.aspects. RESULTS: A
significant correlation was found between several job satisfaction factors and
intention to leave in this study group, including quality of supervision, level
of competency to do the job, recognition for doing the job, advancement
opportunities, autonomy, feelings of worthwhile accomplishment, communication and
support from the manager. CONCLUSION: In relation to Herzberg's job satisfaction
theory, both intrinsic and extrinsic work factors have been shown to have a
significant correlation with intention to leave in this study group. This
information can assist workforce planners to implement strategies to improve
retention levels of allied health professionals in the work place.
PMID- 25844983
TI - Electronic Alteration on Oligothiophenes by o-Carborane: Electron Acceptor
Character of o-Carborane in Oligothiophene Frameworks with Dicyano-Vinyl End-On
Group.
AB - We studied electronic change in oligothiophenes by employing o-carborane into a
molecular array in which one or both end(s) were substituted by electron
withdrawing dicyano-vinyl group(s). Depending on mono- or bis-substitution at the
o-carborane, a series of linear A1-D-A2 (1a-1c) or V-shaped A1-D-A2-D-A1 (2a-2c)
oligothiophene chain structures of variable length were prepared; A1, D, and A2,
represent dicyano-vinyl, oligothiophenyl, and o-carboranyl groups, respectively.
Among this series, 2a shows strong electron-acceptor capability of o-carborane
comparable to that of the dicyano-vinyl substituent, which can be elaborated by a
conformational effect driven by cage sigma*-pi* interaction. As a result,
electronic communications between o-carborane and dicyano-vinyl groups are
successfully achieved in 2a.
PMID- 25844987
TI - Error in group information and figure.
PMID- 25844984
TI - Selecting the best candidates for lung cancer screening.
PMID- 25844988
TI - Sudden painless nail shedding. Hand-foot-and-mouth disease (HFMD).
PMID- 25844989
TI - JAMA pediatrics patient page. Keeping children and adolescents safe from
firearms.
PMID- 25844990
TI - Association between admission temperature and mortality and major morbidity in
preterm infants born at fewer than 33 weeks' gestation.
AB - IMPORTANCE: Neonatal hypothermia has been associated with higher mortality and
morbidity; therefore, thermal control following delivery is an essential part of
neonatal care. Identifying the ideal body temperature in preterm neonates in the
first few hours of life may be helpful to reduce the risk for adverse outcomes.
OBJECTIVES: To examine the association between admission temperature and neonatal
outcomes and estimate the admission temperature associated with lowest rates of
adverse outcomes in preterm infants born at fewer than 33 weeks' gestation.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational study at 29
neonatal intensive care units in the Canadian Neonatal Network. Participants
included 9833 inborn infants born at fewer than 33 weeks' gestation who were
admitted between January 1, 2010, and December 31, 2012. EXPOSURE: Axillary or
rectal body temperature recorded at admission. MAIN OUTCOMES AND MEASURES: The
primary outcome was a composite adverse outcome defined as mortality or any of
the following: severe neurological injury, severe retinopathy of prematurity,
necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infection.
The relationships between admission temperature and the composite outcome as well
as between admission temperature and the components of the composite outcome were
evaluated using multivariable analyses. RESULTS: Admission temperatures of the
9833 neonates were distributed as follows: lower than 34.5 degrees C (1%); 34.5
degrees C to 34.9 degrees C (1%); 35.0 degrees C to 35.4 degrees C (3%); 35.5
degrees C to 35.9 degrees C (7%); 36.0 degrees C to 36.4 degrees C (24%); 36.5
degrees C to 36.9 degrees C (38%); 37.0 degrees C to 37.4 degrees C (19%); 37.5
degrees C to 37.9 degrees C (5%); and 38.0 degrees C or higher (2%). After
adjustment for maternal and infant characteristics, the rates of the composite
outcome, severe neurological injury, severe retinopathy of prematurity,
necrotizing enterocolitis, bronchopulmonary dysplasia, and nosocomial infection
had a U-shaped relationship with admission temperature (alpha > 0 [P < .05]). The
admission temperature at which the rate of the composite outcome was lowest was
36.8 degrees C (95% CI, 36.7 degrees C-37.0 degrees C). Rates of severe
neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis
(95% CI, 36.3 degrees C-36.7 degrees C), bronchopulmonary dysplasia, and
nosocomial infection (95% CI, 36.9 degrees C-37.3 degrees C) were lowest at
admission temperatures ranging from 36.5 degrees C to 37.2 degrees C. CONCLUSIONS
AND RELEVANCE: The relationship between admission temperature and adverse
neonatal outcomes was U-shaped. The lowest rates of adverse outcomes were
associated with admission temperatures between 36.5 degrees C and 37.2 degrees C.
PMID- 25844991
TI - Risk for incident diabetes mellitus following initiation of second-generation
antipsychotics among Medicaid-enrolled youths.
AB - IMPORTANCE: Second-generation antipsychotics (SGAs) have increasingly been
prescribed to Medicaid-enrolled children, either singly or in a medication
combination. Although metabolic adverse effects have been linked to SGA use in
youths, estimating the risk for type 2 diabetes mellitus, a rarer outcome, has
been challenging. OBJECTIVE: To determine whether SGA initiation was associated
with an increased risk for incident type 2 diabetes mellitus. Secondary analyses
examined the risk associated with multiple-drug regimens, including stimulants
and antidepressants, as well as individual SGAs. DESIGN, SETTING, AND
PARTICIPANTS: Retrospective national cohort study of Medicaid-enrolled youths
between January 2003 and December 2007. In this observational study using
national Medicaid Analytic eXtract data files, initiators and noninitiators of
SGAs were identified in each month. Included in this study were US youths aged 10
to 18 years with a mental health diagnosis and enrolled in a Medicaid fee-for
service arrangement during the study. Those with chronic steroid exposure, a
diagnosis of diabetes mellitus, or SGA use during a 1-year look-back period were
ineligible. The mean follow-up time for all participants was 17.2 months. Youths
were followed up until diagnosis of diabetes mellitus or end of follow-up owing
to censoring caused by the transition into a Medicaid managed care arrangement or
Medicaid ineligibility (the end of available data). Propensity weights were
developed to balance observed demographic and clinical characteristics between
exposure groups. Discrete failure time models were fitted using weighted logistic
regression to estimate the risk for incident diabetes mellitus between initiators
and noninitiators. EXPOSURE: A filled SGA prescription. MAIN OUTCOMES AND
MEASURES: Incident type 2 diabetes mellitus identified through visit and pharmacy
claims during the observation period. RESULTS: Among 107,551 SGA initiators and
1,221,434 noninitiators, the risk for incident diabetes mellitus was increased
among initiators (odds ratio [OR], 1.51; 95% CI, 1.35-1.69; P < .001). Compared
with youths initiating only SGAs, the risk was higher among SGA initiators who
used antidepressants concomitantly at the time of SGA initiation (OR, 1.54; 95%
CI, 1.17-2.03; P = .002) but was not significantly different for SGA initiators
who were concomitantly using stimulants. As compared with a reference group of
risperidone initiators, the risk was higher among those initiating ziprasidone
(OR, 1.61; 95% CI, 0.99-2.64; P = .06) and aripiprazole (OR, 1.58; 95% CI, 1.21
2.07; P = .001) but not quetiapine fumarate or olanzapine. CONCLUSIONS AND
RELEVANCE: The risk for incident type 2 diabetes mellitus was increased among
youths initiating SGAs and was highest in those concomitantly using
antidepressants. Compared with risperidone, newer antipsychotics were not
associated with decreased risk.
PMID- 25844992
TI - Failure to cancel tests: a case of an unnecessary joint arthrocentesis: a
teachable moment.
PMID- 25844993
TI - Neurologic Function and Health-Related Quality of Life in Patients Following
Targeted Temperature Management at 33 degrees C vs 36 degrees C After Out-of
Hospital Cardiac Arrest: A Randomized Clinical Trial.
AB - IMPORTANCE: Brain injury affects neurologic function and quality of life in
survivors after cardiac arrest. OBJECTIVE: To compare the effects of 2 target
temperature regimens on long-term cognitive function and quality of life after
cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter,
international, parallel group, assessor-masked randomized clinical trial
performed from November 11, 2010, through January 10, 2013, we enrolled 950
unconscious adults with cardiac arrest of presumed cardiac cause from 36
intensive care units in Europe and Australia. Eleven patients were excluded from
analysis for a total sample size of 939. INTERVENTIONS: Targeted temperature
management at 33 degrees C vs 36 degrees C. MAIN OUTCOMES AND MEASURES: Cognitive
function was measured by the Mini-Mental State Examination (MMSE) and assessed by
observers through the Informant Questionnaire on Cognitive Decline in the Elderly
(IQCODE). Patients reported their activities in daily life and mental recovery
through Two Simple Questions and their quality of life through the Medical
Outcomes Study 36-Item Short Form Health Survey, version 2. RESULTS: In the
modified intent-to-treat population, including nonsurvivors, the median MMSE
score was 14 in the 33 degrees C group (interquartile range [IQR], 0-28) vs 17 in
the 36 degrees C group (IQR, 0-29) (P = .77), and the IQCODE score was 115 (IQR,
79-130) vs 115 (IQR, 80-130) (P = .57) in the 33 degrees C and 36 degrees C
groups, respectively. The median MMSE score for survivors was within the
reference range and similar (33 degrees C group median, 28; IQR, 26-30; vs 36
degrees C group median, 28; IQR, 25-30; P = .61). The median IQCODE score was
within the minor deficit range (33 degrees C group median, 79.5; IQR, 78.0-85.9;
vs 36 degrees C group median, 80.7; IQR, 78.0-86.9; P = .04). A total of 18.8% vs
17.5% of survivors reported needing help with everyday activities (P = .71), and
66.5% in the 33 degrees C group vs 61.8% in the 36 degrees C group reported that
they thought they had made a complete mental recovery (P = .32). The mean (SD)
mental component summary score was 49.1 (12.5) vs 49.0 (12.2) (P = .79), and the
mean (SD) physical component summary score was 46.8 (13.8) and 47.5 (13.8) (P =
.45), comparable to the population norm. CONCLUSIONS AND RELEVANCE: Quality of
life was good and similar in patients with cardiac arrest receiving targeted
temperature management at 33 degrees C or 36 degrees C. Cognitive function was
similar in both intervention groups, but many patients and observers reported
impairment not detected previously by standard outcome scales. TRIAL
REGISTRATION: ClinicalTrials.gov NCT01020916.
PMID- 25844994
TI - Comorbid Adolescent Difficulties: Social Work Prevention of Delinquency and
Serious Youthful Offending.
AB - A majority of adolescents who are formally involved with the juvenile courts and
detained or incarcerated are dealing with past or present maltreatment
victimization, learning disabilities, and/or mental health/substance abuse
difficulties. Addressing these problems and traumas is an integral part of
preventing delinquency and breaking a youthful offender's recidivist cycle, a
pattern that often predicts adult offending and incarceration. Fortunately, there
are effective programs across the social work profession that decrease or may
even eliminate delinquent behaviors, both for low-level and more serious youthful
offenders. Unfortunately, the use of these social work preventative programs is
not consistent or extensive within the juvenile justice system.
PMID- 25844995
TI - Surgery versus nonsurgical treatment of lumbar spinal stenosis: a randomized
trial.
AB - BACKGROUND: Primary care management decisions for patients with symptomatic
lumbar spinal stenosis (LSS) are challenging, and nonsurgical guidance is limited
by lack of evidence. OBJECTIVE: To compare surgical decompression with physical
therapy (PT) for LSS and evaluate sex differences. DESIGN: Multisite randomized,
controlled trial. (ClinicalTrials.gov: NCT00022776). SETTING: Neurologic and
orthopedic surgery departments and PT clinics. PARTICIPANTS: Surgical candidates
with LSS aged 50 years or older who consented to surgery. INTERVENTION: Surgical
decompression or PT. MEASUREMENTS: Primary outcome was physical function score on
the Short Form-36 Health Survey at 2 years assessed by masked testers. RESULTS:
The study took place from November 2000 to September 2007. A total of 169
participants were randomly assigned and stratified by surgeon and sex (87 to
surgery and 82 to PT), with 24-month follow-up completed by 74 and 73
participants in the surgery and PT groups, respectively. Mean improvement in
physical function for the surgery and PT groups was 22.4 (95% CI, 16.9 to 27.9)
and 19.2 (CI, 13.6 to 24.8), respectively. Intention-to-treat analyses revealed
no difference between groups (24-month difference, 0.9 [CI, -7.9 to 9.6]).
Sensitivity analyses using causal-effects methods to account for the high
proportion of crossovers from PT to surgery (57%) showed no significant
differences in physical function between groups. LIMITATION: Without a control
group, it is not possible to judge success attributable to either intervention.
CONCLUSION: Surgical decompression yielded similar effects to a PT regimen among
patients with LSS who were surgical candidates. Patients and health care
providers should engage in shared decision-making conversations that include full
disclosure of evidence involving surgical and nonsurgical treatments for LSS.
PRIMARY FUNDING SOURCE: National Institutes of Health and National Institute of
Arthritis and Musculoskeletal and Skin Diseases.
PMID- 25844996
TI - The optimal imaging strategy for patients with stable chest pain: a cost
effectiveness analysis.
AB - BACKGROUND: The optimal imaging strategy for patients with stable chest pain is
uncertain. OBJECTIVE: To determine the cost-effectiveness of different imaging
strategies for patients with stable chest pain. DESIGN: Microsimulation state
transition model. DATA SOURCES: Published literature. TARGET POPULATION: 60-year
old patients with a low to intermediate probability of coronary artery disease
(CAD). TIME HORIZON: Lifetime. PERSPECTIVE: The United States, the United
Kingdom, and the Netherlands. INTERVENTION: Coronary computed tomography (CT)
angiography, cardiac stress magnetic resonance imaging, stress single-photon
emission CT, and stress echocardiography. OUTCOME MEASURES: Lifetime costs,
quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.
RESULTS OF BASE-CASE ANALYSIS: The strategy that maximized QALYs and was cost
effective in the United States and the Netherlands began with coronary CT
angiography, continued with cardiac stress imaging if angiography found at least
50% stenosis in at least 1 coronary artery, and ended with catheter-based
coronary angiography if stress imaging induced ischemia of any severity. For U.K.
men, the preferred strategy was optimal medical therapy without catheter-based
coronary angiography if coronary CT angiography found only moderate CAD or stress
imaging induced only mild ischemia. In these strategies, stress echocardiography
was consistently more effective and less expensive than other stress imaging
tests. For U.K. women, the optimal strategy was stress echocardiography followed
by catheter-based coronary angiography if echocardiography induced mild or
moderate ischemia. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to
changes in the probability of CAD and assumptions about false-positive results.
LIMITATIONS: All cardiac stress imaging tests were assumed to be available.
Exercise electrocardiography was included only in a sensitivity analysis.
Differences in QALYs among strategies were small. CONCLUSION: Coronary CT
angiography is a cost-effective triage test for 60-year-old patients who have
nonacute chest pain and a low to intermediate probability of CAD. PRIMARY FUNDING
SOURCE: Erasmus University Medical Center.
PMID- 25844998
TI - Celebrating the ACP Centennial: From the Annals archive-firearm-related harms.
PMID- 25844999
TI - Surgery for lumbar spinal stenosis: informed patient preferences should weigh
heavily.
PMID- 25844997
TI - Efficacy of commercial weight-loss programs: an updated systematic review.
AB - BACKGROUND: Commercial and proprietary weight-loss programs are popular obesity
treatment options, but their efficacy is unclear. PURPOSE: To compare weight
loss, adherence, and harms of commercial or proprietary weight-loss programs
versus control/education (no intervention, printed materials only, health
education curriculum, or <3 sessions with a provider) or behavioral counseling
among overweight and obese adults. DATA SOURCES: MEDLINE and the Cochrane
Database of Systematic Reviews from inception to November 2014; references
identified by program staff. STUDY SELECTION: Randomized, controlled trials
(RCTs) of at least 12 weeks' duration; prospective case series of at least 12
months' duration (harms only). DATA EXTRACTION: Two reviewers extracted
information on study design, population characteristics, interventions, and mean
percentage of weight change and assessed risk of bias. DATA SYNTHESIS: We
included 45 studies, 39 of which were RCTs. At 12 months, Weight Watchers
participants achieved at least 2.6% greater weight loss than those assigned to
control/education. Jenny Craig resulted in at least 4.9% greater weight loss at
12 months than control/education and counseling. Nutrisystem resulted in at least
3.8% greater weight loss at 3 months than control/education and counseling. Very
low-calorie programs (Health Management Resources, Medifast, and OPTIFAST)
resulted in at least 4.0% greater short-term weight loss than counseling, but
some attenuation of effect occurred beyond 6 months when reported. Atkins
resulted in 0.1% to 2.9% greater weight loss at 12 months than counseling.
Results for SlimFast were mixed. We found limited evidence to evaluate adherence
or harms for all programs and weight outcomes for other commercial programs.
LIMITATION: Many trials were short (<12 months), had high attrition, and lacked
blinding. CONCLUSION: Clinicians could consider referring overweight or obese
patients to Weight Watchers or Jenny Craig. Other popular programs, such as
Nutrisystem, show promising weight-loss results; however, additional studies
evaluating long-term outcomes are needed. PRIMARY FUNDING SOURCE: None. (
PROSPERO: CRD4201-4007155).
PMID- 25845000
TI - The role of commercial weight-loss programs.
PMID- 25845001
TI - Homesick: from Beirut to Rochester.
PMID- 25845003
TI - Genetic and environmental risk assessment and colorectal cancer screening.
PMID- 25845004
TI - Genetic and environmental risk assessment and colorectal cancer screening.
PMID- 25845005
TI - 3D-CAM.
PMID- 25845006
TI - 3D-CAM.
PMID- 25845007
TI - Prevention of recurrent nephrolithiasis in adults.
PMID- 25845008
TI - Prevention of recurrent nephrolithiasis in adults.
PMID- 25845009
TI - Prevention of recurrent nephrolithiasis in adults.
PMID- 25845010
TI - Models in the development of clinical practice guidelines.
PMID- 25845011
TI - Models in the development of clinical practice guidelines.
PMID- 25845012
TI - Chikungunya.
PMID- 25845013
TI - Chikungunya.
PMID- 25845014
TI - Chikungunya.
PMID- 25845015
TI - Correction: Inviting patients to read their doctors' notes.
PMID- 25845016
TI - Summaries for patients. Surgery versus physical therapy for treating lumbar
spinal stenosis.
PMID- 25845018
TI - Web Exclusives. Annals graphic medicine: Betty P.
PMID- 25845017
TI - In the clinic. Constipation.
AB - This issue provides a clinical overview of constipation, focusing on prevention,
diagnosis, treatment, and patient information. The content of In the Clinic is
drawn from the clinical information and education resources of the American
College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical
Knowledge and Self-Assessment Program). Annals of Internal Medicine editors
develop In the Clinic from these primary sources in collaboration with the ACP's
Medical Education and Publishing divisions and with the assistance of science
writers and physician writers. Editorial consultants from ACP Smart Medicine and
MKSAP provide expert review of the content. Readers who are interested in these
primary resources for more detail can consult http://smartmedicine.acponline.org,
http://mksap.acponline.org, and other resources referenced in each issue of In
the Clinic.
PMID- 25845019
TI - Necrotrophic effector epistasis in the Pyrenophora tritici-repentis-wheat
interaction.
AB - Pyrenophora tritici-repentis, the causal agent of tan spot disease of wheat,
mediates disease by the production of host-selective toxins (HST). The known
toxins are recognized in an 'inverse' gene-for-gene manner, where each is
perceived by the product of a unique locus in the host and recognition leads to
disease susceptibility. Given the importance of HSTs in disease development, we
would predict that the loss of any of these major pathogenicity factors would
result in reduced virulence and disease development. However, after either
deletion of the gene encoding the HST ToxA or, reciprocally, heterologous
expression of ToxA in a race that does not normally produce the toxin followed by
inoculation of ToxA-sensitive and insensitive wheat cultivars, we demonstrate
that ToxA symptom development can be epistatic to other HST-induced symptoms.
ToxA epistasis on certain ToxA-sensitive wheat cultivars leads to genotype
specific increases in total leaf area affected by disease. These data indicate a
complex interplay between host responses to HSTs in some genotypes and underscore
the challenge of identifying additional HSTs whose activity may be masked by
other toxins. Also, through mycelial staining, we acquire preliminary evidence
that ToxA may provide additional benefits to fungal growth in planta in the
absence of its cognate recognition partner in the host.
PMID- 25845020
TI - Influence of institutional culture and policies on do-not-resuscitate decision
making at the end of life.
AB - IMPORTANCE: Controversy exists regarding whether the decision to pursue a do-not
resuscitate (DNR) order should be grounded in an ethic of patient autonomy or in
the obligation to act in the patient's best interest (beneficence). OBJECTIVE: To
explore how physicians' approaches to DNR decision making at the end of life are
shaped by institutional cultures and policies surrounding patient autonomy.
DESIGN, SETTING, AND PARTICIPANTS: We performed semistructured in-depth
qualitative interviews of 58 internal medicine physicians from 4 academic medical
centers (3 in the United States and 1 in the United Kingdom) by years of
experience and medical subspecialty from March 7, 2013, through January 8, 2014.
Hospitals were selected based on expected differences in hospital culture and
variations in hospital policies regarding prioritization of autonomy vs best
interest. MAIN OUTCOMES AND MEASURES: This study identified the key influences of
institutional culture and policies on physicians' attitudes toward patient
autonomy in DNR decision making at the end of life. RESULTS: A hospital's
prioritization of autonomy vs best interest as reflected in institutional culture
and policy appeared to influence the way that physician trainees conceptualized
patient autonomy. This finding may have influenced the degree of choice and
recommendations physician trainees were willing to offer regarding DNR decision
making. Trainees at hospitals where policies and culture prioritized autonomy
focused approaches appeared to have an unreflective deference to autonomy and
felt compelled to offer the choice of resuscitation neutrally in all situations
regardless of whether they believed resuscitation to be clinically appropriate.
In contrast, trainees at hospitals where policies and culture prioritized best
interest-focused approaches appeared to be more comfortable recommending against
resuscitation in situations where survival was unlikely. Experienced physicians
at all sites similarly did not exclusively allow their actions to be defined by
policies and institutional culture and were willing to make recommendations
against resuscitation if they believed it would be futile. CONCLUSIONS AND
RELEVANCE: Institutional cultures and policies might influence how physician
trainees develop their professional attitudes toward autonomy and their
willingness to make recommendations regarding the decision to implement a DNR
order. A singular focus on autonomy might inadvertently undermine patient care by
depriving patients and surrogates of the professional guidance needed to make
critical end of life decisions.
PMID- 25845021
TI - Recovery and recurrence following a first episode of mania: a systematic review
and meta-analysis of prospectively characterized cohorts.
AB - OBJECTIVE: Information about recurrence rates is useful in informing clinical
practice, but most data with regard to recurrence rates in bipolar patients come
from cohorts at different stages of illness. These data are of limited utility in
estimating risk of relapse in first-episode bipolar disorder. Therefore, the
objective of this investigation was to synthesize available recurrence data after
a first episode of mania. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO,
and Cochrane Central Register of Controlled Trials (CENTRAL) from 1980 to January
24th, 2014, for articles in English, French, or Spanish using (1) bipolar
disorder (MeSH term) OR manic/mania, AND (2) first* (episode*, hospitalization*
OR admission*) OR time factor (MeSH term), AND (3) recovery, remission,
recurrence OR relapse. STUDY SELECTION: 712 articles were screened. Prospective
cohorts of first-episode mania were included. DATA EXTRACTION: Syndromal
recovery, symptomatic recovery, and recurrence rates were extracted by 2
independent raters at 6 months, 1 year, 2 years, and 4 years and analyzed using
random effects models and meta-regression. RESULTS: We identified 8 studies
representing a total of 734 first-episode patients. The syndromal recovery rates
were 77.4% at 6 months and 84.2% at 1 year. Only 62.1% of patients had achieved a
period of symptomatic recovery within 1 year. Recurrence rates were 25.7% within
6 months, 41.0% by 1 year, and 59.7% by 4 years. Younger age at first episode was
associated with risk of recurrence after 1 year. CONCLUSIONS: The majority of
patients with first-episode mania exhibit syndromal recovery and, to a lesser
extent, symptomatic recovery. The risk of recurrence is high, although the rates
are slightly lower than those in mixed cohorts, with greater risk of recurrence
associated with younger age at onset. Given lower recurrence than among mixed
cohorts, there may be a window of opportunity to provide optimal treatment early
and alter disease progression.
PMID- 25845022
TI - VEGF and dual-EGFR inhibition in colorectal cancer.
PMID- 25845023
TI - Orthogonal thiol functionalization at a single atomic center for profiling
transthiolation activity of E1 activating enzymes.
AB - Transthiolation is a fundamental biological reaction and is utilized by many
enzymes involved in the conjugation of ubiquitin and ubiquitin-like proteins.
However, tools that enable selective profiling of this activity are lacking.
Transthiolation requires cysteine-cysteine juxtaposition; therefore a method that
enables irreversible "stapling" of proximal thiols would facilitate the
development of novel probes that could be used to profile this activity. Herein,
we characterize biocompatible chemistry that enables sequential functionalization
of cysteines within proteins at a single atomic center. We use our method to
develop a new class of activity-based probe that profiles transthiolation
activity of human E1 activating enzymes. We demonstrate use in vitro and in situ
and compatibility with competitive activity-based protein profiling. We also use
the probe to gain insight into the determinants of transthiolation between E2 and
a RING-in-between-RING (RBR) E3 ligase. Furthermore, we anticipate that this
method of thiol functionalization will have broad utility by enabling simple
redox-stable cross-linking of proximal cysteines in general.
PMID- 25845024
TI - Bio-inspired direct patterning functional nanothin microlines: controllable
liquid transfer.
AB - Developing a general and low-cost strategy that enables direct patterning of
microlines with nanometer thickness from versatile liquid-phase functional
materials and precise positioning of them on various substrates remains a
challenge. Herein, with inspiration from the oriental wisdom to control ink
transfer by Chinese brushes, we developed a facile and general writing strategy
to directly pattern various functional microlines with homogeneous distribution
and nanometer-scale thickness. It is demonstrated that the width and thickness of
the microlines could be well-controlled by tuning the writing method, providing
guidance for the adaptation of this technique to various systems. It is also
shown that various functional liquid-phase materials, such as quantum dots, small
molecules, polymers, and suspensions of nanoparticles, could directly write on
the substrates with intrinsic physicochemical properties well-preserved.
Moreover, this technique enabled direct patterning of liquid-phase materials on
certain microdomains, even in multiple layered style, thus a microdomain
localized chemical reaction and the patterned surface chemical modification were
enabled. This bio-inspired direct writing device will shed light on the template
free printing of various functional micropatterns, as well as the integrated
functional microdevices.
PMID- 25845025
TI - Modeling Pulmonary Disease Pathways Using Recombinant Adeno-Associated Virus 6.2.
AB - Viral vectors have been applied successfully to generate disease-related animal
models and to functionally characterize target genes in vivo. However, broader
application is still limited by complex vector production, biosafety
requirements, and vector-mediated immunogenic responses, possibly interfering
with disease-relevant pathways. Here, we describe adeno-associated virus (AAV)
variant 6.2 as an ideal vector for lung delivery in mice, overcoming most of the
aforementioned limitations. In a proof-of-concept study using AAV6.2 vectors
expressing IL-13 and transforming growth factor-beta1 (TGF-beta1), we were able
to induce hallmarks of severe asthma and pulmonary fibrosis, respectively.
Phenotypic characterization and deep sequencing analysis of the AAV-IL-13 asthma
model revealed a characteristic disease signature. Furthermore, suitability of
the model for compound testing was also demonstrated by pharmacological
intervention studies using an anti-IL-13 antibody and dexamethasone. Similarly,
the AAV-TGF-beta1 fibrosis model showed several disease-like pathophenotypes
monitored by micro-computed tomography imaging and lung function measurement.
Most importantly, analyses using stuffer control vectors demonstrated that in
contrast to a common adenovirus-5 vector, AAV6.2 vectors did not induce any
measurable inflammation and therefore carry a lower risk of altering relevant
readouts. In conclusion, we propose AAV6.2 as an ideal vector system for the
functional characterization of target genes in the context of pulmonary diseases
in mice.
PMID- 25845026
TI - Application of Pediatric and Adult Guidelines for Treatment of Lipid Levels Among
US Adolescents Transitioning to Young Adulthood.
AB - IMPORTANCE: Health care practitioners who care for adolescents transitioning to
adulthood often face incongruent recommendations from pediatric and adult
guidelines for treatment of lipid levels. OBJECTIVE: To compare the proportion of
young people aged 17 to 21 years who meet criteria for pharmacologic treatment of
elevated low-density lipoprotein cholesterol (LDL-C) levels under pediatric vs
adult guidelines. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross
sectional analysis of the National Health and Nutrition Examination Survey
(NHANES) population. Surveys were administered from January 1, 1999, through
December 31, 2012, and the analysis was performed from June through December
2014. Participants included 6338 individuals aged 17 to 21 years in the United
States. MAIN OUTCOMES AND MEASURES: To estimate the number and proportion of
individuals aged 17 to 21 years in the NHANES population who were eligible for
statin therapy, we applied treatment algorithms from the 2011 Integrated
Guidelines for Cardiovascular Health and Risk Reduction in Children and
Adolescents of the National Heart, Lung, and Blood Institute and the 2013
Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic
Cardiovascular Risk in Adults from the American College of Cardiology and
American Heart Association. After imputing missing data and applying NHANES
sampling weights, we extrapolated the results to 20.4 million
noninstitutionalized young people aged 17 to 21 years living in the United
States. RESULTS: Of the 6338 young people aged 17 to 21 years in the NHANES
population, 2.5% (95% CI, 1.8%-3.2%) would qualify for statin treatment under the
pediatric guidelines compared with 0.4% (95% CI, 0.1%-0.8%) under the adult
guidelines. Participants who met pediatric criteria had lower mean (SD) LDL-C
levels (167.3 [3.8] vs 210.0 [7.1] mg/dL) but higher proportions of other
cardiovascular risk factors, including hypertension (10.8% vs 8.4%), smoking
(55.0% vs 23.9%), and obesity (67.7% vs 18.2%) compared with those who met the
adult guidelines. Extrapolating to the US population of individuals aged 17 to 21
years represented by the NHANES sample, 483 500 (95% CI, 482 100-484 800) young
people would be eligible for treatment of LDL-C levels if the pediatric
guidelines were applied compared with only 78 200 (95% CI, 77 600-78 700) if the
adult guidelines were applied. CONCLUSIONS AND RELEVANCE: Application of
pediatric vs adult guidelines for lipid levels, which consider additional
cardiovascular risk factors beyond age and LDL-C concentration, might result in
statin treatment for more than 400 000 additional adolescents and young adults.
PMID- 25845027
TI - Highly Active Gold(I)-Silver(I) Oxo Cluster Activating sp3 C-H Bonds of Methyl
Ketones under Mild Conditions.
AB - The activation of C(sp(3))-H bonds is challenging, due to their high bond
dissociation energy, low proton acidity, and highly nonpolar character. Herein we
report a unique gold(I)-silver(I) oxo cluster protected by hemilabile phosphine
ligands [OAu3Ag3(PPhpy2)3](BF4)4 (1), which can activate C(sp(3))-H bonds under
mild conditions for a broad scope of methyl ketones (RCOCH3, R = methyl, phenyl,
2-methylphenyl, 2-aminophenyl, 2-hydroxylphenyl, 2-pyridyl, 2-thiazolyl, tert
butyl, ethyl, isopropyl). Activation happens via triple deprotonation of the
methyl group, leading to formation of heterometallic Au(I)-Ag(I) clusters with
formula RCOCAu4Ag4(PPhpy2)4(BF4)5 (PPhpy2 = bis(2-pyridyl)phenylphosphine).
Cluster 1 can be generated in situ via the reaction of [OAu3Ag(PPhpy2)3](BF4)2
with 2 equiv of AgBF4. The oxo ion and the metal centers are found to be
essential in the cleavage of sp(3) C-H bonds of methyl ketones. Interestingly,
cluster 1 selectively activates the C-H bonds in -CH3 rather than the N-H bonds
in -NH2 or the O-H bond in -OH which is traditionally thought to be more reactive
than C-H bonds. Control experiments with butanone, 3-methylbutanone, and
cyclopentanone as substrates show that the auration of the C-H bond of the
terminal methyl group is preferred over secondary or tertiary sp(3) C-H bonds; in
other words, the C-H bond activation is influenced by steric effect. This work
highlights the powerful reactivity of metal clusters toward C-H activation and
sheds new light on gold(I)-mediated catalysis.
PMID- 25845028
TI - Spatially Mapping Energy Transfer from Single Plasmonic Particles to
Semiconductor Substrates via STEM/EELS.
AB - Energy transfer from plasmonic nanoparticles to semiconductors can expand the
available spectrum of solar energy-harvesting devices. Here, we spatially and
spectrally resolve the interaction between single Ag nanocubes with insulating
and semiconducting substrates using electron energy-loss spectroscopy,
electrodynamics simulations, and extended plasmon hybridization theory. Our
results illustrate a new way to characterize plasmon-semiconductor energy
transfer at the nanoscale and bear impact upon the design of next-generation
solar energy-harvesting devices.
PMID- 25845029
TI - The Flocculating Cationic Polypetide from Moringa oleifera Seeds Damages
Bacterial Cell Membranes by Causing Membrane Fusion.
AB - A cationic protein isolated from the seeds of the Moringa oleifera tree has been
extensively studied for use in water treatment in developing countries and has
been proposed for use in antimicrobial and therapeutic applications. However, the
molecular basis for the antimicrobial action of this peptide, Moringa oleifera
cationic protein (MOCP), has not been previously elucidated. We demonstrate here
that a dominant mechanism of MOCP antimicrobial activity is membrane fusion. We
used a combination of cryogenic electron microscopy (cryo-EM) and fluorescence
assays to observe and study the kinetics of fusion of membranes in liposomes
representing model microbial cells. We also conducted cryo-EM experiments on E.
coli cells where MOCP was seen to fuse the inner and outer membranes. Coarse
grained molecular dynamics simulations of membrane vesicles with MOCP molecules
were used to elucidate steps in peptide adsorption, stalk formation, and fusion
between membranes.
PMID- 25845030
TI - Solvent accessible surface area-based hot-spot detection methods for protein
protein and protein-nucleic acid interfaces.
AB - Due to the importance of hot-spots (HS) detection and the efficiency of
computational methodologies, several HS detecting approaches have been developed.
The current paper presents new models to predict HS for protein-protein and
protein-nucleic acid interactions with better statistics compared with the ones
currently reported in literature. These models are based on solvent accessible
surface area (SASA) and genetic conservation features subjected to simple Bayes
networks (protein-protein systems) and a more complex multi-objective genetic
algorithm-support vector machine algorithms (protein-nucleic acid systems). The
best models for these interactions have been implemented in two free Web tools.
PMID- 25845031
TI - Cancer information seekers in china: a preliminary profile.
AB - Cancer is now the leading cause of death in China. Effective communication about
cancer risk and prevention is an important component of cancer control. Yet,
research in this area is very limited in China. This study used probability
sample survey data from 2 Chinese cities (Beijing and Hefei, Anhui Province) to
investigate potential predictors of self-initiated cancer information seeking.
Analysis showed that cancer information seekers in China were likely to be
married, relatively educated, earning modest incomes, living in rural areas,
smoking occasionally, having a family cancer history, relatively trusting of the
media for health information, somewhat knowledgeable about cancer, having
nonfatalistic attitudes about cancer, and seeing a personal need for more cancer
information. The pattern of results, particularly the lack of influence of
personal health and risk perception factors, highlights the possibility that
seeking for others might be more prevalent than seeking for self in China.
Overall, findings suggest that emphasizing family need and mobilizing family
support might be a productive approach to cancer communication interventions in
China.
PMID- 25845033
TI - The use of novel oral anticoagulants: the debate continues!
PMID- 25845034
TI - The treatment of venous thromboembolism with novel oral anticoagulants: warnings
and limitations.
PMID- 25845035
TI - Which patients with venous thromboembolism should receive non-vitamin K
antagonist oral anticoagulants? The majority.
PMID- 25845036
TI - Antipsychotic prescriptions in Iraq and Afghanistan veterans with posttraumatic
stress disorder in Department of Veterans Affairs healthcare, 2007-2012.
AB - OBJECTIVE: Antipsychotic medications have been increasingly prescribed for off
label uses, including treatment of posttraumatic stress disorder (PTSD). Given
limited knowledge about their use in returning Iraq and Afghanistan veterans with
PTSD, we explored rates of antipsychotic use in this population and correlations
with sociodemographic, military service, and psychiatric factors. METHOD: Iraq
and Afghanistan veterans with a PTSD diagnosis based on ICD-9-CM codes enrolled
in Veterans Administration care between January 1, 2007, and September 30, 2011,
were followed through September 30, 2012. Patients with a comorbid diagnosis of
schizophrenia or bipolar disorder were excluded. Poisson regression models
evaluated factors associated with prescriptions for antipsychotic versus other
psychiatric medications (primary outcome). RESULTS: The mean age of our study
population was 29.3 years, and 9.4% were women. Of 186,460 veterans with PTSD
diagnoses examined, 19.9% received no psychiatric medications, and the remainder
received psychiatric medications that excluded (61.2%) or included (18.9%)
antipsychotics. In adjusted models, several factors were independently associated
with antipsychotic use, including male sex (adjusted relative risk = 1.25; 95%
CI, 1.20-1.30) and enlisted rank (1.44; 95% CI, 1.35-1.53). Increased likelihood
of antipsychotic prescribing was associated with suicidal ideation (4.77; 95% CI,
4.59-4.95) and comorbid psychiatric diagnoses including personality disorder
(4.27; 95% CI, 4.09-4.46), drug use disorder (3.56; 95% CI, 3.43-3.69), and
alcohol use disorder (2.75; 95% CI, 2.65-2.84). CONCLUSIONS: A substantial
minority of Iraq and Afghanistan veterans diagnosed with PTSD received
antipsychotics. Male veterans, those of enlisted rank, and those with suicidal
ideation and psychiatric comorbidities were more likely to receive antipsychotics
than other types of psychiatric medications. Providers should be cautious about
antipsychotic use, given their known metabolic risks and questionable benefits
for PTSD.
PMID- 25845037
TI - [In memory of Vasily Khristoforovich Anestiadi].
PMID- 25845038
TI - Author's reply: To PMID 25254521.
PMID- 25845039
TI - Author's reply: To PMID 25003687.
PMID- 25845040
TI - Author's reply.
PMID- 25845041
TI - Author's reply.
PMID- 25845042
TI - Author's reply: To PMID 24818624.
PMID- 25845043
TI - Author's reply.
PMID- 25845045
TI - Author's reply.
PMID- 25845044
TI - Author's reply.
PMID- 25845046
TI - PDX-1 (pancreatic/duodenal homeobox-1 protein 1).
AB - The homeodomain-containing transcription factor pancreatic duodenal homeobox 1
(PDX-1) plays a key role in pancreatic development and beta-cell function. It is
a major regulator of transcription in pancreatic cells, and transactivates the
insulin gene by binding to a specific DNA motif in its promoter region. Glucose
also regulates insulin gene transcription through PDX-1. It has been shown that
PDX-1 is required for maintaining pancreatic islet functions by activating gene
expression and has a dual role in pancreatic development. It initially
contributes to pancreatic formation during embryogenesis and subsequently
regulates the pancreatic islet cell physiology in mature islet cells. Because of
this key role in the embryologic development of the pancreas, PDX-1 expression
has been investigated in pancreatic cancer cell lines and human tumors. Moreover,
a few reports have described expression of PDX-1 in other human neoplasms and
have investigated its potential role in differential diagnosis, but data on
normal human tissues are lacking. Understanding the molecular mechanisms of
pancreas formation, and especially the function of PDX-1, may contribute to the
improved treatment and prevention of debilitating diseases such as diabetes,
insulinomas and pancreatic carcinomas. Nevertheless, further studies are needed
concerning its possible application in routine practice.
PMID- 25845047
TI - Lipomatous angiomyofibroblastoma of the vulva: diagnostic and histogenetic
considerations.
AB - We report a rare case of angiomyofibroblastoma (AMFB) of the vulva, composed
predominantly of a mature fatty component, representing approximately 60% of the
entire tumour. The tumour, designated as "lipomatous AMFB", should be interpreted
as the morphological result of an unbalanced bidirectional differentiation of the
presumptive precursor stromal cell resident in the hormonally-responsive stroma
of the lower genital tract, with the adipocytic component overwhelming the
fibroblastic/myofibroblastic one. The close admixture of adipocytes with
spindled/epithelioid cells of the conventional AMFB resulted, focally, in a
pseudo-infiltrative growth pattern and pseudo-lipoblast-like appearance, raising
problems in differential diagnosis, especially with well-differentiated lipoma
like liposarcoma and spindle cell liposarcoma. Awareness of the possibility that
vulvo-vaginal AMFB may contain large amount of lipomatous component is crucial to
avoid confusion with other bland-looking spindle cell tumours containing
infiltrating fat.
PMID- 25845048
TI - A peculiar fibroma-like lesion of superficial soft tissue: morphologic and
immunophenotypic evaluation.
AB - Apeculiar lesion of superficial soft tissue characterised by fibroma-like
morphology and an immunohistochemical profile consisting of CK+, VIM+, CD34+,
CD31+/-, FLI1+ and INI-1 retained is described. The lesion entered into
differential diagnosis with the so-called fibroma-like variant of epithelioid
sarcoma, with the entities defined as ES-like/pseudomyogenic
haemangioendothelioma and the recently identified entity defined as superficial
CD34+ fibroblastic tumour. All of these entities share a common morphological
structure, but differ in their immunophenotypic profile.
PMID- 25845049
TI - Mixed stromal and smooth muscle tumours of the uterus: a report of two cases.
AB - Mixed stromal and smooth muscle uterine tumours, defined as those containing at
least 30% of each component as seen by routine light microscopy, are rare. This
report describes the morphological features of two such tumours diagnosed in 44
year-old and 50-year-old females complaining from recurrent uterine bleeding that
was unresponsive to medical treatment. Morphological and immunohistochemical
evaluations were performed, and a final diagnosis of mixed endometrial stromal
nodule and smooth muscle tumour of the uterus was rendered in both cases.
PMID- 25845050
TI - Primary mediastinal angiosarcoma: a rare observation in a patient with 8-year
survival.
AB - BACKGROUND: Vascular tumours of the mediastinum are rare, accounting for 1-2% of
all mediastinal tumours in this location. Angiosarcomas are most often
encountered as sporadic lesions, typically in the scalp or face of elderly
patients. However, they can occur in any anatomic site. Mediastinal angiosarcomas
(MA) are very rare with less than 50 cases reported. CASE REPORT: The authors
describe the case of a 38-year-old woman whose past medical history was
consistent for a MA that was diagnosed in 2003. This tumour was treated by
complete surgical resection followed by radiation therapy and chemotherapy.
Diagnosis was based on histologic examination. In 2011, the patient presented a
pleural localisation of the angiosarcoma and died one month after admission, 8
years after diagnosis of the MA. CONCLUSION: MA is a very rare tumour causing a
diagnostic dilemma. Clinical and radiologic findings are non-specific, and final
diagnosis is based on histologic examination. The case described is unusual
considering the long period of survival, which may be explained by the treatment
modalities associating complete surgical resection, chemotherapy and radiation
therapy.
PMID- 25845051
TI - Dermatofibrosarcoma protuberans of the vulva: a mesenchymal tumour with a broad
differential diagnosis and review of literature.
AB - Dermatofibrosarcoma protuberans (DFSP) is a malignant cutaneous soft tissue
tumour, which rarely presents in the vulva. We report an unusual case of this
tumour involving the vulva. A 61-year-old female presented with a mass in the
left mons pubis. Subsequent excisional biopsy of the mass was performed.
Histologic evaluation of the specimen showed a spindle cell lesion consisting of
fibroblast-like cells arranged in a storiform pattern. On average, there were 2
to 3 mitotic figures per 10 high power field (hpf). The neoplastic cells showed
extension into the surrounding fibroadipose tissue. A panel of
immunohistochemical stains including CD34, S-100, melan-A, HMB-45, vimentin and
smooth muscle actin (SMA) were tested. The neoplastic cells showed diffuse
staining with CD34 and vimentin, while the rest were negative. Based on the
morphologic and immunohistochemical staining pattern, a diagnosis of DFSP was
rendered. The patient underwent two subsequent resections before she had clear
resection margins. The postoperative course was unremarkable. The patient is
disease free without recurrence after a follow-up of 12 months. DFSP infrequently
involves the vulva and should be considered in the differential diagnosis of
other spindle cell lesions presenting in this unusual site. The role of
immunohistochemical staining with CD34 is imperative in establishing the
diagnosis. The rate of local reoccurrence is high, but it rarely shows
metastasis. Treatment of choice is wide local surgical excision with close follow
up to detect reoccur- rence.
PMID- 25845052
TI - Unusual presentation of metastatic adenoid cystic carcinoma: a challenge in
aspiration cytology of the thyroid.
AB - INTRODUCTION: Adenoid cystic carcinoma is a malignant neoplasm most commonly
originating in the salivary glands. Its occurrence elsewhere is rare and its
metastasis to the thyroid gland has been described only once. CASE REPORT: We
describe the case of a 66-year-old man who presented for a swelling in the
midline neck of six months duration. A solitary palpable nodule was identified in
the isthmic region of the thyroid. Fine needle aspiration of the nodule revealed
high cellularity, a partial microfollicle-like pattern and the presence of small
hyaline globules. The neoplastic population was composed of monomorphic cells
with basaloid appearance. Thyroid primitivity was excluded on the basis of the
negativity for TTF1 and thyroglobulin. As the patient referred an ulcerative
lesion of the inferior lip, fine needle aspiration cytology of the lesion was
performed, yielding a diagnosis of adenoid cystic carcinoma. CONCLUSION: The
present case highlights the need to be aware of possible metastatic thyroid
localisation of adenoid cystic carcinoma also originating in minor salivary
glands of the oral cavity. This is a very rare event, but it should be taken into
consideration and clinical and cytological findings must be carefully examined.
PMID- 25845054
TI - [The responsibility of the physician before the Judiciary Accountant after an
innovative address coordination given by the Prosecutor of Lazio].
PMID- 25845053
TI - Gastrointestinal stromal tumour of the stomach with osseous differentiation: a
case report.
AB - Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasm
of the gastrointestinal tract, while osseous metaplasia of this tumour is an
unexpected event. To date, no cases have been reported in the literature. Herein,
we report a case of a 60-year-old man affected by a GIST with benign osseous
metaplasia and mature bone formation. We also discuss the pathogenesis of
intratumoural ossification and review the relevant literature. The prognostic
significance of ossification in GIST remains unclear because of the limited cases
reported.
PMID- 25845055
TI - [Prospective general risk in Anatomical Pathology].
PMID- 25845056
TI - Preliminary findings from the Oranga Niho dental student outplacement project.
AB - OBJECTIVES: To examine stakeholder perspectives of the Bachelor of Dental Surgery
2012-2013 clinical outplacement programme with Maori Oral Health Providers
(MOHPs) and inform the programme's ongoing development. DESIGN: A mixed methods
kaupapa Maori action research project. SETTING: Six North Island MOHPs and the
University of Otago Faculty of Dentistry. PARTICIPANTS AND METHODS: Online
questionnaires were used to conduct a pre- and post-outplacement survey of dental
students and a twice-yearly survey of all MOHP-based clinical supervisors. Paper
questionnaires were used to survey adult clients and caregivers of child clients
that the students treated. Data were analysed descriptively and thematically.
MAIN OUTCOME MEASURES: 68 (61%) of the 112 eligible students completed the pre-
and post-outplacement questionnaires; 31 clinical supervisor questionnaire
responses were received representing all six MOHPs; and 426 client and 130
caregiver questionnaire responses were received from five MOHPs. RESULTS: 79% of
students felt well prepared for outplacement and 75% indicated that they would
consider working for a MOHP in future. Of the clinical supervisors, 93% indicated
that the students were adequately prepared for outplacement, and 68%, that they
would recommend one or more students for employment. However, 58% associated the
outplacements with decreased productivity. More than 97% of adult clients and
caregivers of child clients were pleased with the care that the students
provided. CONCLUSION: Recommendations for strengthening the outplacement
programme included: increasing communication between the Faculty, MOHPs and
students; addressing the financial cost of the programme to the MOHPs; and
providing more support for clinical supervisors.
PMID- 25845057
TI - An exploratory study of parental knowledge of early childhood oral health care in
Southland, New Zealand.
AB - OBJECTIVES: The primary objective was to clearly assess the oral health care
knowledge of Southland parents. The secondary objective was to identify whether
inequalities exist between parents with different ethnicity, education or income.
DESIGN: An exploratory study based on a simple online/ paper questionnaire.
SETTING: Participants were recruited through Southland early childcare centres.
Researchers contacted 115 centres, 66 agreed to participate and 58 returned
questionnaires. METHODS: Questionnaires were distributed to each centre to be
completed by the parents. The questionnaire was able to be completed online or as
a paper copy. Centres were supplied with dental brochures, which were distributed
after the questionnaires were returned. Questionnaires were collated and the
responses analysed. RESULTS: Six hundred and seventy questionnaires were
returned, 213 online and 457 paper copies. The typical participant was a mother
(93.9%), age 34 years (median), a non-smoker (86.3%), non-Maori (87.1%), with a
university degree (33.9%) and an annual household income between $60,001 and
$100,000 (36.5%). Twenty of the 47 questions were selected to reflect parental
knowledge. Overall, 65.1% of the respondents answered all 20 questions correctly.
Differences in knowledge were identified between mothers and other participants
(65.4% vs. 59.4%), smokers and non-smokers (61.3% vs. 65.7%), Maori and non-Maori
(61.6% vs. 65.6%) and education level (Primary 58.0% vs. Degree 68.7%) (P <
0.05). CONCLUSIONS: This study revealed differences in knowledge in early
childhood oral health care. Participants who identified as non-mothers (fathers,
step-fathers, legal care givers or other), smokers, Maori or low education
displayed significantly less knowledge. Further education and oral health care
promotion may be needed to improve this disparity.
PMID- 25845058
TI - The impact of patient's complaints on New Zealand dentists.
AB - BACKGROUND AND OBJECTIVES: This study aimed to investigate the impact of
receiving a patient complaint on dentists in New Zealand. METHOD: A qualitative
research method was chosen to investigate the experience of dentists in receipt
of a complaint. Nine dentists practising in New Zealand who had received
complaints from a variety of sources were interviewed. All volunteered having
responded to requests and advertisements seeking participants for the study. In
depth interviews with line-by-line transcript analysis allowed the discovery of
themes and subthemes related to the impact of complaints. RESULTS: Receiving a
complaint was a stressful experience for these dentists. Anxiety, loss of
confidence, fear of loss of income and altered relationships with complainants
characterised respondents' personal responses. Dentists were distracted from
family time by the complaint, and their families experienced upset and anxiety.
Anxiety spread within the practice to colleagues and staff. Respondents and their
staff had to cope with difficult and at times abusive behaviour from complainants
and their families. Dentists reported feeling helpless, struggling with lack of
timeliness, the need for a satisfactory and meaningful resolution and the impact
of third parties, particularly in the genesis of the complaint. They were aware
of costs incurred by patients. They sought meaningful support but sometimes late
in the process. For these respondents the complaint led to few changes in their
practice. CONCLUSION: Receiving a complaint is a stressful experience and
dentists need appropriate emotional as well as legal support. The responsibility
for this lies with the wider profession.
PMID- 25845059
TI - The Securinega alkaloids.
AB - Securinega alkaloids represent a family of plant secondary metabolites known for
50 years. Securinine (1), the most abundant and studied alkaloid of this series
was isolated by Russian researchers in 1956. In the following years, French and
Japanese scientists reported other Securinega compounds and extensive work was
done to elucidate their intriguing structures. The homogeneity of this family
relies mainly on its tetracyclic chemical backbone, which features a butenolide
moiety (cycle D) and an azabicyclo[3.2.1]octane ring system (rings B and C).
Interestingly, after a period of latency of 20 years, the Securinega topic
reemerged as a prolific source of new natural structures and to date more than 50
compounds have been identified and characterized. The oligomeric subgroup
gathering dimeric, trimeric, and tetrameric units is of particular interest. The
unprecedented structure of the Securinega alkaloids was the subject of extensive
synthetic efforts culminating in several efficient and elegant total syntheses.
The botanical distribution of these alkaloids seems limited to the Securinega,
Flueggea, Margaritaria, and Breynia genera (Phyllanthaceae). However, only a
limited number of plant species have been considered for their alkaloid contents,
and additional phytochemical as well as genetic studies are needed. Concerning
the biosynthesis, experiments carried out with radiolabelled aminoacids allowed
to identify lysine and tyrosine as the precursors of the piperidine ring A and
the CD rings of securinine (1), respectively. Besides, plausible biosynthetic
pathways were proposed for virosaine A (38) and B (39), flueggine A (46), and
also the different oligomers flueggenine A-D (48-51), fluevirosinine A (56), and
flueggedine (20). The case of nirurine (45) and secu'amamine (37) remains elusive
and additional studies seem necessary to understand their mode of production. The
scope of biological of activities of the Securinega alkaloids was mainly centered
on the CNS activity of securinine (1), although the exact mechanism of action
remained in part unknown. Nevertheless, for its stimulant and antispasmodic
effects securinine nitrate was marketed as a drug in the USSR until the early
1990s. Moreover, securinine (1) and several other Securinega alkaloids recently
demonstrated promising anticancer properties. In particular securinine (1)
demonstrated markedly benefits in the treatment of acute myeloid leukemia.
PMID- 25845060
TI - The homalium alkaloids: isolation, synthesis, and absolute configuration
assignment.
AB - The structurally related natural products (-)-homaline, (-)-hopromine, (-)
hoprominol, and (-)-hopromalinol have been collectively termed the homalium
alkaloids. All four alkaloids possess bis-zeta-azalactam structures, but differ
only by the identities of the side chain on each lactam ring. Since their
isolation (from the leaves of Homalium pronyense Guillaum found in the forests of
New Caledonia), there have been several syntheses of homaline, hopromine,
hoprominol, and hopromalinol in both racemic and enantiopure forms. The most
highly yielding and versatile strategy for their synthesis employs the conjugate
addition of an enantiopure lithium amide reagent to an alpha,beta-unsaturated
ester as the key stereodefining step. This methodology has been used in the
syntheses of all four members of the homalium alkaloid family and their
stereoisomers.
PMID- 25845061
TI - The alkaloids of the madangamine group.
AB - This chapter is focused on madangamines, a small group of complex diamine
alkaloids isolated from marine sponges of the order Haplosclerida, and covers
their isolation, characterization, biogenesis, biological activity, and
synthesis. Structurally, madangamines are pentacyclic alkaloids with an
unprecedented skeletal type, characterized by a common diazatricyclic core and
two peripheral macrocyclic rings. The isolation of these alkaloids from
Xestospongia ingens (madangamines A-E) and Pachychalina alcaloidifera
(madangamine F) is described in detail. Physical and complete spectroscopic 1H
and 13C NMR data are included. The proposed biogenesis of madangamines from
ammonia, a functionalized three-carbon unit, and saturated or unsaturated linear
long-chain dialdehydes, via partially reduced bis-alkylpyridine macrocycles, is
discussed. The synthesis of alkaloids of the madangamine group has been little
explored, with only one total synthesis reported so far, that of (+)-madangamine
D. This review also describes several model synthetic approaches to the
diazatricyclic ABC core of these alkaloids, as well as model studies on the
construction of the (Z,Z)-unsaturated 11-membered E macrocycle common to
madangamines A-E, the 13- and 14-membered D rings of madangamines C-E, and the
all-cis-triunsaturated 15-membered D ring of madangamine A. Some members of this
group have shown significant in vitro cytotoxicity against a number of cancer
cell lines.
PMID- 25845062
TI - The Veratrum and Solanum alkaloids.
AB - This survey on steroidal alkaloids of the Veratrum and Solanum family isolated
between 1974 and 2014 includes 187 compounds and 197 references. New developments
in the chemistry and biology of this family of natural products with a special
focus on the medicinal relevance of the jervanine alkaloid cyclopamine are
discussed.
PMID- 25845063
TI - Alkaloids of the Annonaceae: occurrence and a compilation of their biological
activities.
AB - This chapter presents an overview of the chemistry and pharmacology of the
alkaloids found in species of the Annonaceae family. The occurrence of alkaloids
from Annonaceae species, as well as their chemical structures and pharmacological
activities are summarized in informative and easy-to-understand tables. Within
the Annonaceae family, the genera Annona, Duguetia, and Guatteria have led to
many important publications. Valuable and comprehensive information about the
structure of these alkaloids is provided. The alkaloids of the aporphine type
represent the predominant group in this family. Many of the isolated alkaloids
exhibit unique structures. In addition to the chemical structures, the
pharmacological activities of some alkaloids are also presented in this chapter.
Thus, the leishmanicidal, antimicrobial, antitumor, cytotoxic, and antimalarial
activities observed for these alkaloids are highlighted. The chapter is presented
as a contribution for the scientific community, mainly to enable the search for
alkaloids in species belonging to the Annonaceae family.
PMID- 25845064
TI - Integrated community case management of sick children in Ethiopia. Foreword.
PMID- 25845065
TI - Introduction to a special supplement: delivering integrated community case
management to treat childhood illness at scale in Ethiopia.
PMID- 25845066
TI - Integrated community case management of childhood illnesses: adaptations for the
developing regions of Ethiopia.
PMID- 25845067
TI - From integrated community case management to community-based newborn care.
PMID- 25845068
TI - Can training health extension workers in the integrated pharmaceutical logistics
system (IPLS) be effective, affordable, and opportunistic?
PMID- 25845069
TI - How do Ethiopia's health extension workers spend their time?
PMID- 25845070
TI - National scale-up of integrated community case management in rural Ethiopia:
implementation and early lessons learned.
AB - BACKGROUND: Although under-five mortality in Ethiopia has decreased 67% in the
past two decades, many, children still die from preventable or treatable
conditions, mainly pneumonia, newborn problems, diarrhea, malaria and
malnutrition. Most of these deaths can be avoided with timely and appropriate
care, but access to and use of treatment remains inadequate. Community health
workers, appropriately trained, supervised, and supplied with essen- tial
equipment and medicines, can deliver case management or referral to most sick
children. In 2010, Ethiopia added pneumonia to diarrhea, malaria and severe acute
malnutrition, targeted for treatment in the integrated community case management
(iCCM) strategy. PURPOSE: This article describes the national scale-up of iCCM
implementation and early lessons learned. METHODS: We reviewed data related to
iCCM program inputs and processes from reports, minutes, and related documents
from January 2010 through July 2013. We describe introduction and scale-up
through eight health system components. RESULTS: The government and partners
trained and supplied 27,116 of the total 32,000 Health Extension Workers and
mentored 80% of them to deliver iCCM services to over one million children. The
government led a strong-iCCM partnership that attracted development partners in
implementation, monitoring, evaluation, and research. Service utilization and
weak supply chain remain-major challenges. CONCLUSION: Strong MOH leadership,
policy support, and national partnerships helped successful national iCCM scale
up and should help settle remaining challenges.
PMID- 25845071
TI - Performance of Ethiopia's health system in delivering integrated community-based
case management.
AB - BACKGROUND: Analyzing complex health programs by their components and sub
components serves design, documentation, evaluation, research, and gap
identification and prioritization. In 2012, we developed a rapid methodology to
characterize integrated community case management (iCCM) programs, by assessing
benchmarks for eight health system components in three program phases. OBJECTIVE.
To assess iCCM benchmarks in Ethiopia three years after scale-up commenced, and
to compare the benchmarks across the geographical region. METHODS. Six national
iCCM experts scored each of 70 benchmarks (no, partial, or yes) and then were
facilitated to reach consensus. RESULTS. Overall, iCCM benchmark achievement in
Ethiopia was high (87.3%), highest for pre-introduction (93.0%), followed by
introduction (87.9%) and scale-up (78.1%) phases. Achievement by system component
was highest for coordination and policy (94.2%) and lowest for costing and
finance (70.3%). Six regional, countries benchmark assessments, including two
from Ethiopia 14 months apart, were highly correlated with program duration at
scale (correlation coefficient: +0.88). CONCLUSION: Ethiopia has a mature, broad
based iCCM program. Despite limitations, the method described here rapidly,
systematically, and validly characterized a complex program and highlighted areas
for attention through government or partners.
PMID- 25845072
TI - Coverage and equitability of interventions to prevent child mortality in rural
Jimma and West Hararghe Zones, Oromia Region, Ethiopia.
AB - BACKGROUND: Interventions to prevent childhood illnesses are important components
of the Ethiopian Health Extension Program (HEP). Although the HEP was designed to
reduce inequities in access to health care, there is little evidence on
equitability of preventive interventions in Ethiopia. PURPOSE: This article
describes coverage of preventive interventions and how many interventions
individual children received We also examined which factors were associated with
the number of preventive interventions received, and assessed the extent to which
interventions were equitably distributed. METHODS: We conducted a cross-sectional
survey in 3,200 randomly selected households in the rural Jimma and West Hararghe
Zones of Ethiopia's Oromia Region. We calculated coverage of 10 preventive
interventions and a composite of eight interventions (co-coverage) representing
the number of interventions received by children. Mul- tiple linear regressions
were used to assess associations between co-coverage and explanatory variables.
Finally, we assessed the equitability of preventive interventions by comparing
coverage among children in the poorest and the least poor wealth quintiles.
RESULTS: Coverage was less than 50% for six of the 10 interventions. Children
received on average only three of the eight interventions included in the co
coverage calculation. Zone, gender, caretaker age, religion, and household wealth
were all significantly associated with co-coverage, controlling for key
covariates. Exclusive breastfeeding, vaccine uptake, and vitamin A
supplementation were all relatively equitable. On the other hand, coverage of
insecticide-treated nets or indoor residual spraying (ITN/IRS) and access to safe
water were significantly higher among the least poor children compared to
children in the poorest quintile. CONCLUSION: Coverage of key interventions to
prevent childhood illnesses is generally low in Jimma and West Hararghe. Although
a number of interventions were equitably distributed, there were marked wealth
based inequities for interventions that are possessed at the household level,
even among relatively homogeneous rural communities.
PMID- 25845073
TI - Utilization of integrated community case management services in three regions in
Ethiopia after two years of implementation.
AB - BACKGROUND: The integrated community case management (iCCM) strategy has brought
fully integrated treatment for sick children to the community in Ethiopia since
2010. OBJECTIVES: To describe patterns of use of iCCM services in 31 woredas
(districts) in three regions of Ethiopia. METHODS: We analyzed all 60,452
encounters (58,341 [98.2%] for children 2-59 months of age and 2079 [1.8%] for
children < 2 months of age) recorded in iCCM registration books from December 24,
2012 to January 15, 2013 in 622 randomly sampled health posts. RESULTS: Children
2-23 months constituted more than half (58.9%) of the total children treated, and
about half of the registered infants < 2 months (1000/2079 [48.1%]) were not sick
since some Health Extension Workers (HEWs) were recording well-infant visits. On
average, sick children had 1.3 symptoms, more among children 2-59 months than
among young infants (1.4 vs. 1.04, respectively). The main classifications for
children 2-59 months were diarrhea with some or no dehydration (29.8%), pneumonia
(20.7%), severe uncomplicated malnutrition (18.5%), malaria (11.2%), and other
severe diseases (4.0%). More than half the sick children < 2 months (52.7%) had
very severe disease. Treatment rates (per 1000 children per year) were low for
all classifications: 11.9 for malaria (in malarious kebeles only), 20.3 for
malnutrition, 21.2 for pneumonia, and 29.2 for diarrhea with wide regional
variations, except for pneumonia. Nearly two-thirds of health posts (64%) treated
<= 5 cases/month, but one treated 40. Health Extension Workers saw 60% more sick
children 2-59 months in the third quarter of 2012 than in the third quarter of
2011. CONCLUSION: The use of iCCM services is low and increasing slowly, and the
few busy health posts deserve further study. Recording healthy young infants in
sick registers complicates tracking this vulnerable group.
PMID- 25845074
TI - Effect of the health extension program and other accessibility factors on care
seeking behaviors for common childhood illnesses in rural Ethiopia.
AB - BACKGROUND: In January 2011, Health Extension Workers (HEWs) of Ethiopia's Health
Extension Program (HEP) began providing pneumonia case management for children
less than five years of age through the integrated Community Case Management
(iCCM) strategy. OBJECTIVE: To report the effect of HEP, following the
introduction of iCCM, and other accessibility factors on care-seeking behaviors
for common childhood illnesses (acute respiratory infection [ARI], diarrhea, and
fever). METHODS: Three possible care-seeking outcomes for childhood illnesses
were considered: not seeking appropriate care, seeking care from HEP sources, or
seeking care from other appropriate sources. The baseline care-seeking outcomes
from the Ethiopian Demographic and Health Survey, 2011, were compared with the
care-seeking outcomes in a follow-up iCCM survey in December 2012. The effects of
the HEP intensity and other factors on care-seeking outcomes were estimated using
regression analyses. RESULTS: Appropriate care-seeking for children with acute
respiratory infection, ARI, diarrhea, or fever increased two-fold, from 19% at
baseline to 38% at follow-up, mainly due to an increase in seeking care for
common child- hood illnesses from HEWs. Higher intensity of the HEP and other
accessibility factors were associated with higher care-seeking for childhood
illnesses from HEP sources. CONCLUSION: Incorporating iCCM within the HEP service
package significantly improved the appropriate care-seeking behaviors for
childhood illnesses in rural Ethiopia.
PMID- 25845075
TI - Effectiveness of supportive supervision on the consistency of integrated
community cases management skills of the health extension workers in 113
districts of Ethiopia.
AB - BACKGROUND: Consistency in the adherence to integrated Community Case Management
(iCCM) protocols for common childhood illnesses provided by Ethiopia's Health
Extension Program (HEP) frontline workers. One approach is to provide regular
clinical mentoring to the frontline health workers of the HEP at their health
posts (HP) through supportive supervision (SS) following the initial training.
OBJECTIVE: To Assess the effectiveness of visits to improve the consistency of
iCCM skills (CoS) of the HEWs in 113 districts in Ethiopia. METHODS: We analyzed
data from 3,909 supportive supervision visits between January 2011 and June 2013
in 113 districts in Ethiopia. From case assessment registers, a health post was
classified as consistent in managing pneumonia, malaria, or diarrhea cases if the
disease classification, treatment, and follow-up of the last two cases managed at
the health posts were consistent with the protocol. We used regression models to
assess the effects of SS on CoS. RESULTS: All HPs (2,368) received at least one
supportive supervision visit, 41% received two, and 15% received more than two.
During the observation period, HP management consistency in pneumonia, malaria,
and diarrhea increased by 3.0, 2.7 and 4.4-fold, respectively. After controlling
for secular trend and other factors, significant dose-response relationships were
observed between number of SS visits and CoS indicators. CONCLUSIONS: The SS
visits following the initial training were effective in improving the CoS.
PMID- 25845076
TI - Effect of performance review and clinical mentoring meetings (PRCMM) on recording
of community case management by health extension workers in Ethiopia.
AB - BACKGROUND: The Performance Review and Clinical Mentoring Meeting (PRCMM) is an
approach to improve and sustain Health Extension Worker (HEW) skills and
performance in integrated Community Case Management (iCCM). OBJECTIVE: To compare
HEW performance in recording case management before and after they participated
in PRCMM. METHODS: We conducted a historical cohort analysis of iCCM case records
between September 2010 and December 2012 from 622 randomly selected health posts
representing 31 intervention woredas (districts) of Amhara, Oromia and Southern
Nations Nationalities and Peoples' Regions. We used longitudinal regression
analysis comparing the trend in the consistency of the classification with the
assessment, treatment and follow-up date as well as caseload in the periods
before and after PRCMM, with 5511 and 7901 case records, respectively. RESULTS:
Overall consistency improved after PRCMM for all common classifications as
follows: pneumonia (54.1% [95% CI: 47.7%-60.5%] vs. 78.2% [73.9%-82.5%]), malaria
(50.8% [42.9%-58.7%] vs. 78.9% [73.4%- 84.4%]), and diarrhea (33.7% [27.9%-39.5%]
vs. 70.0% [64.7%-75.3%]). This improvement was consistently observed comparing
the six months before and the six months after PRCMM in all the common
classifications except for malaria where the improvement observed during the
first three post-PRCMM months disappeared during the fifth and sixth months.
Caseload increased significantly after PRCMM (6.6 [95% CI: 5.9-7.3] vs. 9.2 [8.5
9.9] cases/health post/month). CONCLUSION: PRCMM seemed to improve iCCM
performance of HEWs and should be integrated within the PHC system and given
about every six months, at least at first, to sustain improvement.
PMID- 25845077
TI - Integrated community case management: quality of care and adherence to medication
in Beneshangul-Gumuz Region, Ethiopia.
AB - BACKGROUND: The International Rescue Committee (IRC) supports implementation of
integrated Community Case Management (iCCM) in all 20 woredas (districts) of
Benishangul Gumuz Region (BSG) in Ethiopia. OBJECTIVES: To identify the gaps in
the provision of quality iCCM services provided by Health Extension Workers
(HEWs) and to assess caregivers' adherence to prescribed medicines for children
under five years of age. METHODS: We conducted a cross-sectional descriptive
study with both quantitative and qualitative study methods. We interviewed 233
HEWs and 384 caregivers, reviewed HEW records of 1,082 cases, and organized eight
focus groups. RESULTS: Most cases (98%) seen by HEWs were children 2-59 months
old, and 85% of the HEWs did not see any sick young infant. The HEWs' knowledge
on assessments and classification and need for referral of cases was above 80%.
However; some reported challenges, especially in carrying out assessment
correctly and not checking for danger signs. Over 90% of caretakers reported
compliance with HEWs' prescription. CONCLUSION: Partners have successfully
deployed trained HEWs who can deliver iCCM according to protocol; however,
additional support is needed to assure a supply of medicines and to mobilize
demand for services, especially for young infants.
PMID- 25845078
TI - Quality and use of IMNCI services at health center under-five clinics after
introduction of integrated community-based case management (ICCM) in three
regions of Ethiopia.
AB - BACKGROUND: The Integrated Management of New born and Childhood Illness (IMNCI)
and the related Integrated Community Case Management (iCCM) are evidence-based
strategies to reduce childhood mortality in Ethiopia at health centres and
community health posts, respectively. The effect of introducing iCCM on IMNCI is
not known. OBJECTIVE: To assess the caseload and quality of lMNCI service in
under-five clinics in health centres after iCCM implementation. METHODS: This
cross-sectional study used register review to assess the IMNCI service use
(before and after iCCM, in 2010 and 2012, respectively) and quality throughout
the period in randomly selected health centers in three regions of the Integrated
Family Health Program (Oromia, SNNPR [Southern Nations and Nationalities and
Peoples Region] and Tigray). RESULTS: Caseload of sick children at 28 health
centers increased by 16% after iCCM implementation (21,443 vs. 24,882 children in
2010 and 2012, respectively. The consistency of IMNVCI treatment with
classification for pneumonia, diarrhea and malaria was low (78, 45, and 67%,
respectively) compared to iCCM treatment (86, 80, and 91%, respectively).
CONCLUSION: Health center case load increased modestly after iCCM was introduced,
but was lower than expected, even when combined with health post use from other
studies. The demand strategy for sick children needs review. The quality of IMNCI
needs improving even to bring it to the quality of iCCM at health posts, as
measured by the same methods. Successful quality assurance approaches from iCCM,
e.g., the Performance Review and Clinical Mentoring Meeting, could be adapted for
IMNCI.
PMID- 25845079
TI - Effect of integrated community case management of common childhood illnesses on
the quality of malaria case management provided by health extension workers at
health posts.
AB - INTRODUCTION: The Integrated Family Health Program supported the government of
Ethiopia to implement the Integrated Community Case Management (iCCM) strategy to
control childhood illness of which malaria is a major cause. OBJECTIVE: To assess
the effect of ICCM training on quality of malaria case management at health
posts. METHODS: . A comparative cross-sectional study was conducted among 170
Health Extension Workers (HEW) providing either integrated or vertical malaria
case management for children less than five years of age in 14 woredas
(districts) of West Hararghe Zone using a multi-stage sampling procedure. HEWs in
seven intervention woredas were trained in malaria case management and rapid
diagnostic test (RDT) procedures through iCCM, and HEWs in comparison woredas
were trained vertically through the national malaria control program. Performance
was assessed using interview, review of registers, and observation of RDT
procedure. RESULTS: Intervention HEWs performed better than their counterparts in
correct drug prescription (90.8 vs. 81.0%, p = 0.03), treatment duration (97.7
vs. 89.9%, p = 0.001), and treatment schedule (95.4 vs. 75.9%, p = 0.000).
Intervention HEWs recorded case management with more consistency than their
counterparts (>= 80% consistency between: classification and assessment [23.0 vs.
3.8%; p = 0.000], classification and treatment [24.1 vs. 7.6%; p = 0.003], and
classification and follow up [24.1% vs. 0.0%; p = 0.000]); however, there is room
for improvement. CONCLUSION: ICCM training has a positive effect on the quality
of malaria case management at the community level.
PMID- 25845080
TI - Factors influencing the low utilization of curative child health services in
Shebedino District, Sidama Zone, Ethiopia.
AB - BACKGROUND: Use and coverage of curative interventions for childhood pneumonia,
diarrhea, and malaria were low in Ethiopia before integrated community-based case
management (iCCM). OBJECTIVES: To examine factors accounting for low use of
iCCMin Shebedino District applying a "Pathway to Sur- vival" approach to assess
illness recognition; home care; labeling and decision-making; patterns of care
seeking; access, availability and quality of care; and referral. METHODS: Shortly
after introduction of iCCM, we conducted five studies in Shebedino District in
May 2011: a population-based household survey; focus group discussions of mothers
of recently ill children; key informant in- terviews, including knowledge
assessment, with Health Extension Workers at health posts and with health workers
at health centers; and an inventory of drugs, supplies, and job aids at health
posts and health centers. RESULTS: The many barriers to use of evidence-based
treatment included: (1) home remedies of uncertain effect and safety that delay
care-seeking; (2) absent decision-maker; (3) fear of stigma; (4) expectation of
non-availability of service or medicine; (5) geographic and financial barriers;
(6) perception of (or actual) poor quality of care; and (7) accessible,
available, affordable, reliable, non-standard, alternative sources of care.
CONCLUSION: Only a system-strengthening approach can overcome such manifold
barriers to use of curative care that has not increased much after ICCM
introduction.
PMID- 25845081
TI - Assessment of the monitoring and evaluation system for integrated community case
management (ICCM) in Ethiopia: a comparison against global benchmark indicators.
AB - BACKGROUND: Program managers require feasible, timely, reliable, and valid
measures of iCCM implementation to identify problems and assess progress. The
global iCCM Task Force developed benchmark indicators to guide implementers to
develop or improve monitoring and evaluation (M&E) systems. OBJECTIVE: To
assesses Ethiopia's iCCM M&E system by determining the availability and
feasibility of the iCCM benchmark indicators. METHODS: We conducted a desk review
of iCCM policy documents, monitoring tools, survey reports, and other rele- vant
documents; and key informant interviews with government and implementing partners
involved in iCCM scale-up and M&E. RESULTS: Currently, Ethiopia collects data to
inform most (70% [33/47]) iCCM benchmark indicators, and modest extra effort
could boost this to 83% (39/47). Eight (17%) are not available given the current
system. Most benchmark indicators that track coordination and policy, human
resources, service delivery and referral, supervision, and quality assurance are
available through the routine monitoring systems or periodic surveys. Indicators
for supply chain management are less available due to limited consumption data
and a weak link with treatment data. Little information is available on iCCM
costs. CONCLUSION: Benchmark indicators can detail the status of iCCM
implementation; however, some indicators may not fit country priorities, and
others may be difficult to collect. The government of Ethiopia and partners
should review and prioritize the benchmark indicators to determine which should
be included in the routine M&E system, especially since iCCMdata are being
reviewed for addition to the HMIS. Moreover, the Health Extension Worker's
reporting burden can be minimized by an integrated reporting approach.
PMID- 25845082
TI - Modeling potential reduction of child mortality after national scale-up of
community-based treatment of childhood illnesses in Ethiopia.
AB - BACKGROUND: Since 2010, 28,000 female health extension workers (IEWs) received
training and support to provide integrated community based case management (iCCM)
of childhood pneumonia, diarrhea, malaria, and se- vere malnutrition in Ethiopia.
OBJECTIVE: We conducted a modeling exercise using two scenarios to project the
potential reduction of the under five mortality, riate due io the iCCM program in
the four agrarian regions of Ethiopia. METHODS. We created three projections: (1)
baseline projection without iCCM; (2) a "moderate" projection using 2012 coverage
data scaled up to 30% by 2015 and (3) a "best case" scenario scaled up to 80%
with 50% of newborns with sepsis receiving effective treatment by 2015. RESULTS.
If the 2012 coverage gains (moderate projection) were applied to the four
agrarian regions, we project that the iCCM program could have saved over 10,000
additional lives per year among children age 1-59 months. If iCCM coverage
reaches the, "best case" scenario, nearly 80,000 additional lives among children
1-59 months of age would be saved between 2012 and 2015. CONCLUSION. High quality
iCCM, delivered and used at scale, is an important contributor to the reduction
of under five mortality in rural Ethiopia. Continued investments in iCCM are
critical to sustaining and improving recent declines in child mortality.
PMID- 25845083
TI - Costing commodity and human resource needs for integrated community case
management in thie differing community health strategies of Ethiopia, Kenya and
Zambia.
AB - BACKGROUND: To ensure correct and appropriate funding is available, there is a
need to estimate resource needs for improved planning and implementation of
integrated Community Case Management (iCCM). OBJECTIVE: To compare and estimate
costs for commodity and human resource needs for iCCM, based on treatment
coverage rates, bottlenecks and national targets in Ethiopia, Kenya and Zambia
from 2014 to 2016. METHODS: Resource needs were estimated using Ministry of
Health (MoH) targets fronm 2014 to 2016 for implementation of case management of
pneumonia, diarrhea and malaria through iCCM based on epidemiological,
demographic, economic, intervention coverage and other health system parameters.
Bottleneck analysis adjusted cost estimates against system barriers. Ethiopia,
Kenya and Zambia were chosen to compare differences in iCCM costs in different
programmatic implementation landscapes. RESULTS: Coverage treatment rates through
iCCM are lowest in Ethiopia, followed by Kenya and Zambia, but Ethiopia had the
greatest increases between 2009 and 2012. Deployment of health extension workers
(HEWs) in Ethiopia is more advanced compared to Kenya and Zambia, which have
fewer equivalent cadres (called commu- nity health workers (CHWs)) covering a
smaller proportion of the population. Between 2014 and 2016, the propor- tion of
treatments through iCCM compared to health centres are set to increase from 30%
to 81% in Ethiopia, 1% to 18% in Kenya and 3% to 22% in Zambia. The total
estimated cost of iCCM for these three years are USD 75,531,376 for Ethiopia, USD
19,839,780 for Kenya and USD 33,667,742 for Zambia. Projected per capita expen-
diture for 2016 is USD 0.28 for Ethiopia, USD 0.20 in Kenya and USD 0.98 in
Zambia. Commodity costs for pneumonia and diarrhea were a small fraction of the
total iCCM budget for all three countries (less than 3%), while around 80% of the
costs related to human resources. CONCLUSION: Analysis of coverage, demography
and epidemiology data improves estimates of fimding requirements for iCCM.
Bottleneck analysis adjusts cost estimates by including system barriers, thus
reflecting a more accurate estimate of potential resource utilization. Adding
pneumonia and diarrhea interventions to existing large scale community-based
malaria case management programs is likely to require relatively small and
nationally affordable investments. iCCM can be implemented for USD 0.09 to 0.98
per capita per annum, depending on the stage of scale-up and targets set by the
MoH.
PMID- 25845084
TI - A descriptive study of the changes in coverage of preventive and promotive
interventions before and after the introduction of integrated community case
management (ICCM) in Ethiopia.
AB - BACKGROUND: The effect of integrated community case management (iCCM) of common
childhood illness on use of vital preventive services is not known. OBJECTIVE: To
measure the coverage of maternal and child health preventive and promotive
interventions before and after scaling up iCCM. METHODS: In 2011 and 2013, we
conducted cross-sectional, population-based, household coverage surveys in four
Integrated Family Health Program target regions: Amhara, Oromia, SNNP, and
Tigray. RESULTS: Coverage increased for 10 of 15 indicators, mainly for maternal,
immunization, and nutrition services. In some cases, we observed dramatic
increases, i.e., for >= 4 antenatal care visits, antenatal iron and folate, and
exclusive breastfeeding. Some increase occurred even when 2011 levels were
already high, i.e., for immunization. Three indicators remained high and
unchanged (bednet ownership, children sleeping under bednets, and any latrine).
Two indicators decreased (tetanus toxoid and households with >= 2 bednets).
CONCLUSION: Scale-up of iCCM was consistent with increased coverage of most
preventative and promotive interventions, which may contribute to the life-saving
effect of iCCM.
PMID- 25845085
TI - Illness recognition, home care, and care-seeking for sick infants less than two
months of age in Shebedino District, Sidama Zone, Ethiopia.
AB - BACKGROUND: The incidence of newborn and young infant health danger signs is
unknown in Ethiopia. Neverthe- less, experience shows that care-seeking is far
lower than conservative morbidity estimates would project. OBJECTIVES: To examine
illness recognition, home care, decision-making, and care-seeking for sick
infants less than two months of age in Shebedino District, Southern Nations,
Nationalities and Peoples Region in 2011. METHODS: Focus group interviews of
mothers (n = 60) of recently ill children. RESULTS: Mothers reported recognizing
many, but not all, evidence-based newborn danger signs. Home care ranged from
probably harmless to harmful and delayed definitive care-seeking. Decision-making
was widespread, but patterns of care-seeking rarely led to prompt, evidence-based
care. Mothers reported 10 barriers to care- seeking at health posts: lack of
knowledge about availability of curative services, fear of evil eye, social
stigma, perceived financial barrier, perceived young infant fragility, an elder's
contrary advice, distance, husband's re- fusal, fear of injection, and belief in
recovery without medicine. CONCLUSION: Young infants are more vulnerable to
illness than their older counterparts, yet they are less likely to receive the
care they need without a targeted, contextualized communication strategy to
generate demand for case management services that are accessible, available, and
of good quality.
PMID- 25845086
TI - Conclusions: delivering integrated community case management (ICCM) to treat
childhood illness at scale in Ethiopia.
PMID- 25845087
TI - [Left ventricular assist device: which emotional impact on the patient?].
AB - BACKGROUND: Advanced heart failure is a challenging disease; the implantable Left
Ventricular Assist Device (L-VAD) is becoming a good chance for relieving
symptoms and prolong survival in most CHF patients. The emotional impact of L-VAD
implantation is thought to be high but, at present, published data are scant
about that. Aim of this study was to evaluate the modifications of perceived
quality of life (QoL) in a group of patients recently treated with L-VAD
implantation, admitted to a residential cardiac rehabilitation program, and to
compare the results to those obtained in patients awaiting heart transplantation
and recently transplanted. MATERIAL AND METHOD: We enrolled 66 patients (pts)
with a recent implant of L-VAD, 51 with refractory heart failure awaiting heart
transplantation (HT) and 55 recently treated with HT. On day two after admission,
all patients underwent a complete psychometric assessment consisting in the
compilation of: Minnesota Living with Heart Failure Questionnaire (MLHFQ). Beck
Anxiety Inventory (BAI). Beck Depression Inventory-II (BDI-II). RESULTS: L-VAD
recipients had significantly higher scores at MLHFQ. Both the total score and the
2 subscales scores (respectively physical and emotional disturbances) were
statistically significant when compared with post-transplant patients.
Posttransplant pts had the lowest scores regarding anxiety symptoms, while the
bearers of device had the highest ones. The same results were obtained for
depression scores (BDI-II), both in total score and in the subscales (somatic
symptoms and affective symptoms). CONCLUSIONS: With an opening scoring, this
study showed the development of more relevant psychological troubles in patients
treated with L-VAD when compared to those awaiting for heart transplantation and
those transplanted.
PMID- 25845088
TI - Exercise training reduces high mobility group box-1 protein levels in women with
breast cancer: findings from the DIANA-5 study.
AB - PURPOSE: To determine whether exercise training might exert anti-inflammatory
effect by reducing HMGB1 levels in women with breast cancer (BC). METHODS: We
analyzed monocentric data from the DIANA (DIET AND ANDROGENS)-5 PROJECT. Study
population consisted of 94 patients randomized into two groups: 61 patients (53
+/- 8 yrs, training group) were assigned to a structured exercise training
intervention (3 times/week for the first 3 months, and once /week for the
following 9 months); whereas 33 patients (52 +/- 7 yrs, control group) followed
only the general indications to adhere to the life-style intervention suggestions
of the DIANA protocol. At study entry and after 12 months, all patients underwent
cardiopulmonary exercise testing, biochemical as- sessment [HMGB1, high
sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6)]; and lipid and
glycemic profile. RESULTS: There were no significant differences between groups
in baseline clinical and inflammatory profile. Among the training group, only
19/61 patients had high adherence to the exercise intervention. After stratifying
the study population according to the level of adhesion to the exer- cise
intervention, 1-year HMGB1 levels were lower among patients more adherent to
exercise (p for trend = 0.001). Further adjusting for age, body mass index and
baseline values, 1-year HMGB1 levels remained significantly and inversely
associated to the level of adhesion to the exercise intervention (B = -0.97, SE =
0.43, p = 0.01). CONCLUSIONS: Moderate intensity exercise training in BC
survivors is associated with reduced HMGB1 levels that are proportional to the
level of adhesion to the exercise intervention, independently from other
classical inflammatory molecules, suggesting an exercise-induced anti
inflammatory effect mediated by HMGB1.
PMID- 25845089
TI - [Cardiologic evaluation of patients undergoing chemotherapy].
AB - Life expectancy in patients affected by cancer has recently increased because of
early diagnosis and actual therapies. In recent years, Oncology and Cardiology
developed a tight relationship because of common risk factors (i.e., obesity,
smoking, alcool intake, etc...), and for preventing the prothrombotic status due
to cancer and the potential cardiotoxicity of chemotherapy. Cardiotoxicity
incidence is reported from 1% up to 70% in retrospective analyses of drug
protocols, mainly representing by left ventricular dysfunction (both reversible
or irreversible), but also by arrhythmias, hypertension, atrioventricular block,
coronary spasm, and arterial or venous thromboembolism. The early detection of
the chemoterapy induced cardiotoxicity is now mandatory and can be obtained
through a proper patients selection for different treatments and a strict
monitoring during the follow-up period. The role of biomarkers of early cardiac
damage, mainly, troponin I and brain natriuretic peptide-BNP, has been recently
challenged, and algorithms are currently available. In the present paper, we
propose how to perform a cardiological evaluation of patients undergoing
chemotherapy tailored by the known adverse effects of the drugs.
PMID- 25845090
TI - Neurocognitive profile of patients with continuous flow left ventricular assist
device.
AB - The increase of severe heart failure and the consequent reduction of the organ
availability for transplantation has led to, in recent years, the introduction of
the LVAD as replacement therapy to heart transplantation. Severe Heart Failure
patients show cognitive deficits in various domains especially in executive
functions, memory and speed of proceedings, due to different
neurophysiopathological processes including chronic hypoperfusion and subsequent
damage to hippocampal and para-hippocampal cortical areas. It is also known that
these deficits improve after heart transplantation. We carried out a literature
review selecting studies that analyzed the cognitive changes in patients with
severe heart failure after implantation of the Continuous Flow Left Ventricular
Assist Device. According to the inclusion criteria, we selected four studies
since 2005 that presented a comprehensive neurocognitive assessment. The results
show that the cognitive profile, with the implantation of LVAD improves in memory
and executive domains, and this improvements results stable in short-medium time.
The effects would also be independent of the type of flow produced by the device
(pulsatile vs continuous). We believe that further studies are required to
explore the relationship between LVAD and cognitive function in severe heart
failure.
PMID- 25845091
TI - [Erectile dysfunction and cardiovascular disease: focus on].
AB - Erectile dysfunction (ED) is a common clinical problem and its prevalence
increases in frequency with age. ED is a risk marker for major cardiovascular
events independently of other more common risk factors in men with and without
known cardiovascular disease. On the basis of the "artery-size hypothesis"
patients with cardiovascular disease often report ED before disease detection, in
average 3 years. Thus, by an early identification of ED, the cardiol- ogist is
given a unique opportunity to better assess the cardiovascular risk of each
patient. Although there is a general impression that ED has an important
predictive role, its diagnosis in clinical practice is widely suboptimal owing to
misconceptions from the side of the patient and a suboptimal management of the
personal relationship from the side of the physician. This paper explores the
critical connection between ED and cardiovascular disease and evaluates how this
association may influence clinical practice.
PMID- 25845092
TI - [Familial hypercholesterolemia in cardiac rehabilitation: a new field of
interest].
AB - Familial hypercholesterolemia (FH) is a frequently undiagnosed genetic disease
characterized by substantial elevations of low-density lipoprotein cholesterol
(LDL-C). The prevalence of heterozygous FH (HeFH) in the general population is
1:500 inhabitants, while the prevalence of homozygous FH (HoFH) is 1:1,000,000.
If FH is not identified and aggressively treated at an early age, affected
individuals have a 20-fold increased lifetime risk of coronary heart disease
compared with the general population. This narrative review provide a concise
overview of recommendations for diagnosis and treatment of adults and children
with FH, and discuss the utility of considering FH as a comorbidity at the entry
of cardiac rehabilitation programmes.
PMID- 25845093
TI - [The Health Department of Sicily "Regional recommendations for hospital discharge
and communication with patients after admission due to a cardiologic event"
decree].
AB - Mortality and rehospitalizations still remain high after discharge for an acute
cardiologic event. In this context, hospital discharge represents a potential
pitfall for heart disease patients. In the setting of care transitions, the
discharge letter is the main instrument of communication between hospital and
primary care. Communication, besides, is an integral part of high-quality,
patient-centered interventions aimed at improving the discharge process.
Inadequate information at discharge significantly affects the quality of
treatment compliance and the adoption of lifestyle modifications for an effective
secondary prevention. The Health Department of Sicily, in 2013, established a
task force with the aim to elaborate "Regional recommendations for hospital
discharge and communication with patients after admission due to a cardiologic
event", inviting to participate GICR-IACPR and many other scientific societies of
cardiology and primary care, as discharge letter and communication are
fundamental junctions of care transitions in cardiology. These recommendations
have been published as a specific decree and contain: a structured model of
discharge letter, which includes all of the parameters characterizing patients at
high clinical risk, high thrombotic risk and low risk according to the Consensus
document ANMCO/GICR-IACPR/GISE; is thus possible to identify these patients,
choosing consequently the most appropriate follow-up pathways. A particular
attention has been given to the "Medication Reconciliation" and to the
identification of therapeutic targets; an educational Kit, with different forms
on cardiac diseases, risk factors, drugs and lifestyle; a check-list about
information given to the patient and caregivers. The "Recommendations" represent,
in conclusion, the practical realization of the fruitful cooperation between
scientific societies and political-administrative institutions that has been
realized in Sicily in the last years.
PMID- 25845094
TI - [Physiotherapists education and competences for cardiac rehabilitation].
AB - Authors show a summary of educational programs in physiotherapy at the present
time in Italy, just regarding cardiac rehabilitation, treated usually too shortly
and in a not homogenous way between the various academic awarding institution and
suffering for the italian general educational system misaligned with the others
European partners. They presents, according with ICF rules and with accreditated
organization, the essential competences required for that health professional to
deal with accountability needs and problems in cardiac rehabilitation, with
enphasis about the low appeal of the discipline by the physiotherapist even
though her great epidemiologic relevance.
PMID- 25845095
TI - An unusual case of myocardial infarction.
AB - Myocardial infarction may be the result of embolism of calcified material from
the aortic valve or thrombotic formations adhering to the same. We report a case
of late myocardial infarction secondary to embolization from a thrombus adherent
to the aortic valve jutting out in the ostium of the left main coronary artery.
PMID- 25845096
TI - [Aneurysmatic aortic root in bicuspid aortic valve stenosis: mini-invasive
approach with sutureless prosthesis].
AB - The implantation of sutureless bioprosthesis is currently not recommended in
patients affected by bicuspid aortic valve because lacking data and follow up. We
report the first case of a patient affected by bicuspid aortic valve stenosis and
aneurysm of non coronary sinus of Valsalva that underwent a successful
substitution of aneurysmatic sinus and minimal invasive sutureless implantation.
PMID- 25845097
TI - [In defense of the specialty].
PMID- 25845098
TI - [Endoscopic incision of intravesical ureteroceles in patients with duplex
system].
AB - PURPOSE: To evaluate the clinical status and renal function of pa- tients with
duplex system and intravesical ureterocele after drainage by cystoscopy. MATERIAL
AND METHODS: In 9 patients with duplex system and intravesical ureterocele
drainage was performed to present recurrent urinary tract infections (7 children
with episodes of pyelonephritis and sepsis) or obstruction of the urinary
drainage. The mean age was 33 months (range 8-108 months). The thecnique was done
under general anesthesia in the operating room and puncture of the ureterocele
was performed using cystourethroscopy with loop electrode. The minimum follow-up
was 12 months (range 12-48 months) and includes renal ultrasound, renal isotopic
study (Mag3 with furosemide) and-echocystography study in patients with
preoperative vesicoureteral reflux or postoperative urinary tract infection.
RESULTS: The average operative time was 60 minutes. Mean hospital stay was 48
hours. There were no complications during the procedure. In five patients urinary
infection episodes disappeared. Ultrasound demonstrated decreased hydronephrosis
and megaureter. In two patients the differential renal function following the
technique improved. One patient with preoperative split renal function of 14%
required nephrectomy. One patient had postoperative vesicoureteral reflux.
CONCLUSIONS: The drainage of intravesical ureterocele in patients with duplex
system reduces episodes of urinary tract infection and urinary tract dilation.
PMID- 25845099
TI - [Vascular rings, our experience with 18 cases].
AB - AIM: Vascular rings are a rare cause of compression of the trachea and/or the
esophagus, causing stridor and/or severe dysphagia. We present our experience in
the diagnosis and management of vascular rings. METHODS: Retrospective study in
which we analyzed clinical history, diagnosis and management of 18 patients
diagnosed with vascular ring between January 1985 and December 2013. We evaluate
endoscopy as a diagnostic method. RESULTS: A total of 18 patients were included,
with a median age of 2 years. 83.3% (15/18) had some type of symptom: 46.7%
(7/15) had respiratory symptoms such as respiratory distress, stridor, recurrent
respiratory infections, bronchospasm with wheezing or asthma in older children;
20% (3/15) had digestive symptoms such as dysphagia, vomiting and regurgitation;
and 33.3% (5/15) combined respiratory and digestive symptoms. The remaining
patients, 16.7% (3/18) were asymptomatic and the diagnosis was casual. The most
common types of vascular rings were double aortic arch (27.8%) and aberrant
subclavian right artery (27.8%). In 3 cases (16.7%) a Kommerell diverticulum was
associated. 44.4% (n = 8) was operated on, the remaining did not present symp-
toms which justify the intervention (n = 10). 37.5% of patients had postoperative
complications (iatrogenic recurrent paralysis and persistent tracheomalacia).
There was no mortality in our series. The median follow-up was 6.4 years. At the
moment, 88.9% of patients are asymptomatic, and 33.3% have been definitely
discharged. CONCLUSIONS: Vascular rings are rare, and usually presented with
common symptoms in childhood. Therefore, in front of a longstanding and recurrent
respiratory symptoms, or dysphagia, we should think of a vascular ring. Not all
subjects are candidates for surgical correction; therefore a multidisciplinary
evaluation is essential.
PMID- 25845100
TI - [Quality of life and long term results in Hirschsprung's disease].
AB - INTRODUCTION: The most frequent long term side effects of Hirschsprung's disease
(HD) surgery are obstructive problems and fecal incontinence. In this study, we
analyse long term functional results of the two most used surgical techniques
(Duhamel-D- and De la Torre-dlT-) from the patient's point of view, through
quality of life and functionality questionnaires. METHODS: We selected short
segment HD patients >= 4 years) that were operated in our unit from 1996 until
2011. We employed two validated questionnaires: Bowel Function Score (BFS) and
Gastrointestinal Quality of Life Index (GIQLI). Both questionnaires were also
tested in two control age matched groups, each for every arm (controlD or control
dlT). RESULTS: Among 28 preselected patients, 22 (78.6%) answered both
questionnaires. Group D (10 patients) showed more constipation: 60% vs. 16.7% ( p
= 0.01). Patients in group dlT (12 patients) showed more leaks: 58.3 vs. 10% (p =
0.03). Results of both questionnaires were higher (better) in Group D: 16 vs.
12.8 points (BFS, p = 0.007) and 74.1 vs. 69.8 (GIQLI, p = 0.17). The control
group showed an overall better scores than HD patients: 17.2 vs. 14.3 (BFS p =
0.001) and 75.9 vs. 71.8 (GIQLI, p = 0.04). Separately, both groups of patients
showed worse scores when compared with each control group. DISCUSSION: Our
results are similar to other studies, where global scores of functional results
and quality of life are worse in operated HD patients than in age matched
controls. Fecal incontinence has more impact on social scores than constipation.
Due to the fact that our dlT patients have more frequently fecal leaks, their
scores are worse than in the D group. Nevertheless, patients in dlT group are
younger and may improve their results as they get older, as it is often the case
in operated HD patients.
PMID- 25845101
TI - [Cervico-sternotomy for thoracic inlet conditions in children].
AB - BACKGROUND/AIM: Neither cervicotomy nor postero-lateral thoracotomy allow safe
surgical access to the lower cervical spine and high posterior mediastinum with
full control of the vascular and neural structures involved. We report our
favorable experience with cervico-sternotomy for accessing this region. PATIENTS
AND METHODS: Six patients were operated upon between 1998 and 2011 for either
removal of huge cervico-thoracic neural ganglioneuromas (n = 2) or anterior
arthrodesis for congenital (n = 2), neuropathic (n = 1) or osteolytic scoliosis
(n = 1). In all cases, cervicotomy was followed by sternotomy, thymectomy,
division of the innominate vein and dissection of jugular veins, carotid arteries
and vagus nerves. RESULTS: The tumors measured 10.9 x 3.9 x 8.7 cm and 8 x 6 x 5
cm, and involved the paravertebral chain from the aortic arch to the base of the
skull and from the left lung hilus to the thyroid region respectively. In the
scoliosis patients, anterior vertebral fixation between C5 and T5 was readily
feasible. Blood transfusion was avoided. Horner's syndrome and transient
lymphedema were the only complications. Median operative time was 210 minutes
(range 180-240 minutes) and median estimated blood loss was 2.7 cc/kg (0-13.8
cc/kg). Median hospital stay was 7 days (range 5-18 days). CONCLUSIONS: Cervico
sternotomy is an optimal approach for this anatomical region in children. It
offers better exposure of the anterior cervico-thoracic spine and the thoracic
inlet than cervicotomy or thoracotomy. Control of the nervous and vascular
structures was safely achieved in all cases and postoperative discomfort was
surprisingly limited.
PMID- 25845102
TI - [Kidney transplantation in children weighing 11 kg or less].
AB - AIMS OF THE STUDY: To evaluate the outcome of kidney transplantation in children
with low weight. METHODS: Retrospective review of the medical records of patients
weighing 11 kg or less that received kidney transplantation between 2001 and 2013
were retrospectively reviewed. RESULTS: Fifty-nine kidney transplantations were
performed in pediatric patients in our center, 12 of them were performed in
patients weighing 11 kg or less (20%). The mean age of the recipient at the time
of transplantation was 2 years (1-3.5); the mean weight was 9.4 +/- 1.1 kg (8.3
11). The etiology of kidney failure was malformative in 42% of patients,
inherited in 33%, glomerular in 8% and oiler etiologies in 17% of the patients.
Two patients did not receive replacement therapy before transplantation (16.7%),
nine received peritoneal dialysis (75%) and one of them hemodialysis (8.3%).
Eleven of the grafts were from cadaveric donor (91.7%) and one of them from a
living donor (8.3%). The mean donor age was 10 years (0.5-29). There was one case
of acute graft thrombosis (8.3%) and one case of eventration requiring
reoperation; there were no other major complications. Mean follow-up was 59
months (4-130). Overall survival (OS) was 100% at 1 year and 91.7% at 5 years.
There was one death in a patient with mitochondrial disease with a functioning
graft. Graft survival (GS) was 92% at 1 year and 75% at 5 years. CONCLUSION:
Kidney transplantation is the treatment of choice for end-stage kidney failure in
the young child. It provides good results in terms of patient and graft survival.
PMID- 25845103
TI - [Therapeutic approach in urinary tract stones in children].
AB - PURPOSE: Kidney stone disease in children is a rare pathology, with a low
incidence in Spain (1/4,500 hospitalized children). The spontaneous expulsion
rate is about 34-47% which means that more of 50% of children need active
treatment. Paediatric patients forming urinary stones have a high risk of
recurrence, therefore, a standard diagnosis and treatment are needed. We present
our experience in urolithiasis treatment in children. MATERIALS AND METHODS: We
reviewed retrospectively all the patients <= 16 years hospitalized in our
hospital with urolithiasis diagnosis from 2000 to 2013, citing treatment
modality, stone-free rates and complications. RESULTS: A total of 69 patients
with a mean age of 8,2 years (range 1-16 years) were treated in our hospital
during that period. The main clinical presentation was pain (52%). The diagnosis
was made by abdominal ultrasounds in all cases. About localization, 21 lithiasis
were found in distal urether (UD), 8 in medium urether (UM), 3 in proximal
urether (UP) and 13 in renal pelvis (PR). The mean size was 13 mm. 21 (30%)
patients had a spontaneous expulsion of the stone, 14 (20%) patients were treated
with extracorporeal shock wave lithotripsy and in 22 (32%) patients the elected
therapy was ureterosopic stone fragmentation (n = 13) or removal (n = 9). No
complications were observed. The overall stone-free rate was 79% (n = 55).
CONCLUSIONS: Kidney stone disease in children is a rare pathology, with its own
features about diagnosis and treatment, which requires medical care in a
specialized center. The optimal treatment should be considered regarding the age
of the patient, localization and size of the stone, as well as the team
experience.
PMID- 25845104
TI - [Complicated omental cyst after a herniorrhaphy in an infant].
AB - Omental cysts are uncommon benign masses localized in the abdomen. This article
describes the case of a male infant who underwent surgery due to a left inguinal
hernia. During the operation a small omental cyst was found inside the sac that
was resected. The first postoperative days were uneventful but the infant came
back to hospital seven days after. Subsequent imaging and operative findings
revealed a complicated omental cyst. This cyst was removed and the histopathology
report described an inflammatory pseudotumor. The postoperative evolution was
satisfactory and the patient has remained asymptomatic since he was discharged
from hospital. In conclusion, it is important to explore the contents of the
hernial sac during inguinal hernia repair. The finding of a small omental cyst
inside the sac should encourage to study other potential intraabdominal lesions.
PMID- 25845105
TI - [Autoamputated ovarian cysts. A clinical case].
AB - INTRODUCTION: Autoamputation refers to a situation in which a tubo-ovarian
remnant is found free-floating in the abdomino-pelvis, which is a complication of
fetal ovarian cyst causing ovarian torsion in uterus. There have been only 13
reported cases of ovarian autoamputation involving children under 1 years of age.
CLINICAL CASE: We present the case of a 9-month old female with history of
abdominal mass in the 26th week of gestation, who was referred to the pediatric
surgery department with CT findings in an abdominal tumor and negative physical
examination, in laparoscopic examination cystic mass is 6 cm in diameter and no
left ovary. The histopathological examination confirmed an ovarian cyst with
necrotic and hemorrhagic remaining. COMMENTATION: This case is reported because
of the low incidence of pathology, exceptional presentation and the favorable
outcome of the patient with implemented laparoscopic management.
PMID- 25845106
TI - [Human tail: rare lesion with occult spinal dysraphism].
AB - Human tails can be classified as either true tails or pseudotails. True human
tails are rare clinical entities. We describe a newborn with a midline sacral
cutaneous appendage. Magnetic resonance imaging of the lumbosacral area revealed
occult spinal dysraphism with tethered cord and intradural lipoma. Prenatal
diagnosis of left renal agenesis was confirmed on postnatal evaluation. Surgical
excision of the appendage was performed and histopathological examination
demonstrated a true tail. The child recovered uneventfully and has been
asymptomatic for 3 years. Dorsal cutaneous appendages are a marker of underlying
occult spinal dysraphism and requires detailed neuroimaging investigation in
order to prevent irreversible neurological damaged.
PMID- 25845107
TI - [Conservative treatment for omental infarction].
AB - The omental infarction is a pathology that occurs more and more in children due
to the increased use of imaging studies and the increment in overweigth and
obesity. Clinical presentation is characterized by abdominal pain and can be
confused with appendicitis, ileitis, adenitis, among other abdominal conditions.
Definitive diagnosis requires the performance of radiologic investigations and
its treatment may be conservative. We report three cases of omental infarction
with different form of clinical presentation, successfully managed
conservatively.
PMID- 25845108
TI - [Nursing home residents are underserved in dental health care. The greater the
disability status, the greater the care deficit].
PMID- 25845109
TI - [Why did I get upset?].
PMID- 25845110
TI - [Our experts explain... Emin concept - not a remedy].
PMID- 25845111
TI - [Looking over the shoulder].
PMID- 25845112
TI - [Diffusing crisis situations with intervention].
PMID- 25845113
TI - [Nurses as survival experts].
PMID- 25845114
TI - [Nurse led versus physician led care of asthma patients].
PMID- 25845115
TI - [Tackling the shortage of skilled personnel. Nursing care facilities of Vivantes
Forum for Seniors GmbH educates Vietnamese in geriatric nursing care].
PMID- 25845116
TI - [Spouses as caregivers].
PMID- 25845117
TI - [Four types of students].
PMID- 25845118
TI - [Needs of the elderly in communities. Uncovering nursing fields].
PMID- 25845119
TI - [Nursing care during imprisonment: report of experiences and reflections. Eight
months in prison in Italy].
PMID- 25845120
TI - [US president Roosevelt tried to hide the sequelae of his polio infection].
PMID- 25845121
TI - [From GPS orientation devices to sensor mats].
PMID- 25845122
TI - Introduction. Consensus oral anticoagulants: special emphasis on vitamin K
antagonists.
PMID- 25845124
TI - Recommendations for oral anticoagulants.
PMID- 25845123
TI - Anticoagulant agents.
PMID- 25845125
TI - Current Indian scenario on the use of oral anticoagulants.
PMID- 25845126
TI - Monitoring oral anticoagulation therapy.
AB - Although VKAs are often criticised for the need of frequent monitoring, such a
practice is very beneficial. Recommended 12-weekly monitoring, rather than 4
weekly, in patients with consistently stable INRs may help reduce patient
inconvenience. The recommended use of patient self-management of anticoagulation
in motivated and competent patients is further very helpful. In the absence of
laboratory test and antidotes to reverse their effects, the use of NOACs is quite
challenging.
PMID- 25845127
TI - Oral anticoagulation in special population and conditions.
PMID- 25845128
TI - A long way off. 1940.
PMID- 25845129
TI - Education saves lives.
PMID- 25845130
TI - Evaluation of a social marketing campaign to increase awareness of immunizations
for urban low-income children.
AB - OBJECTIVE: To assess community awareness of childhood immunizations and intent to
immunize children after a social marketing immunization campaign. METHODS: We
used 2 interviewer-assisted street-intercept surveys to evaluate awareness of
childhood immunizations and intent to immunize low-income children. The "Take
Control! Immunize" social marketing campaign was developed using a community
based participatory research approach and used billboards, flyers, and various
"walking billboard" (eg, backpacks, pens) to deliver immunization messages in the
community settings. RESULTS: Over 85% of community members recalled the "Take
Control! Immunize" message. Almost half of those who saw the immunization message
indicated that the message motivated them to act, including getting their
children immunized or calling their physician to inquire about their children's
immunizations status. All respondents indicated that immunizations were important
for children and that they were likely or very likely to immunize their children.
Respondents who reported that "Take Control!" messages motivated them to act in
the first intercept survey were significantly more likely than those in the
second intercept to report being likely or very likely to immunize their
children. CONCLUSION: Culturally appropriate social marketing immunization
messages in targeted urban settings can increase parental awareness and
behavioral intention to immunize children.
PMID- 25845131
TI - Factors that affect rate of INR decline after warfarin discontinuation.
AB - BACKGROUND: Despite vast literature on warfarin, optimal strategies for
temporarily discontinuing and restarting warfarin have not been established. To
improve warfarin discontinuation processes, we investigated known medical and
genetic factors that influence stable warfarin dose to determine how well they
predict the time until patients become subtherapeutic after discontinuing
warfarin. METHODS: This was a retrospective cohort study of patients who
temporarily discontinued warfarin before an elective procedure andhad at least 2
international normalized ratio (INR) values available during the discontinuation
period. Data abstracted included date of discontinuation, warfarin dose, INR
values, body surface area, gender, age, indication for warfarin, current
medications, eGFR, and presence of bridging therapy with heparin. DNA variants
were tested in CYP2C9, VKORC1, and CYP4F2 genes. Subjects were excluded if they
received vitamin K, fresh frozen plasma, or prothrombin complexes to reverse
anticoagulation. Asymptotic regression models were used to approximate decline in
INR during warfarin clearance. Spearman correlations and Kruskal-Wallis tests
were used to characterize associations of model estimates with quantitative
variables and for group comparisons, respectively. RESULTS: Other than the
expected association with baseline INR, correlations of model parameter estimates
with clinical variables were generally weak and not statistically significant.
The strongest associations with slope were with serum creatinine and eGFR. There
were no significant associations with CYP2C9, VKORC1, or CYP4F2 DNA variants, but
there were few subjects combined in the nonwild groups for CYP2C9. Estimated
slope showed moderate correlation with observed dose. CONCLUSION: Known clinical
and genetic predictors of therapeutic dose were not found to be strongly
associated with the slope of INR decline after warfarin discontinuation.
PMID- 25845132
TI - Increased patient communication using a process supplementing an electronic
medical record.
AB - BACKGROUND: Importance: Patients with cervical cytology abnormalities may require
surveillance for many years, which increases the risk of management error,
especially in clinics with multiple managing clinicians. National Committee for
Quality Assurance (NCQA) Patient-Centered Medical Home (PCMH) certification
requires tracking of abnormal results and communicating effectively with
patients. OBJECTIVES: The purpose of this study was to determine whether a
computer-based tracking system that is not embedded in the electronic medical
record improves (1) accurate and timely communication of results and (2) patient
adherence to follow-up recommendations. METHODS: Design: Pre/post study using
data from 2005-2012. Intervention implemented in 2008. Data collected via chart
review for at least 18 months after index result. Participants: Pre-intervention:
all women (N = 72) with first abnormal cytology result from 2005-2007. Post
intervention: all women (N = 128) with first abnormal cytology result from 2008
2010. Patients were seen at a suburban, university-affiliated, family medicine
residency clinic. Intervention: Tracking spreadsheet reviewed monthly with
reminders generated for patients not in compliance with recommendations. Main
Outcome and Measures: (1) rates of accurate and timely communication of results
and (2) rates of patient adherence to follow-up recommendations. RESULTS:
Intervention decreased absent or erroneous communication from clinician to
patient (6.4% pre- vs 1.6% post-intervention [P = 0.04]), but did not increase
patient adherence to follow-up recommendations (76.1% pre- vs 78.0% post
intervention [ P= 0.78]). CONCLUSIONS: Use of a spreadsheet tracking system
improved communication of abnormal results to patients, but did not significantly
improve patient adherence to recommended care. Although the tracking system
complies with NCQA PCMH requirements, it was insufficient to make meaningful
improvements in patient-oriented outcomes.
PMID- 25845133
TI - Coronary dissection in a patient with essential thrombocytosis.
AB - A 50-year-old man was admitted to the hospital with left shoulder and arm
discomfort. He had no recent history of change in his energy level, limitations
to activity, exertional chest pain, or shortness of breath. He had cardiac risk
factors, including a strong family history of pre-mature coronary artery disease
and dyslipidemia. He had a syncopal episode in 2003 with a positive troponin I,
but had a negative cardiac workup, including cardiac catheterization that showed
luminal irregularities and no significant coronary artery disease. An
echocardiogram was performed to rule out potential cardiac causes for shoulder
pain and showed regional wall motion abnormalities. Follow-up cardiac
catheterization revealed left anterior descending artery proximal and mid
dissection and a long area of dissection in the first diagonal branch. Laboratory
evaluation showed significant platelet elevation and positive JAK2 study.
Ultrasound of the abdomen revealed moderate splenomegaly. The enlarged spleen,
positive JAK2 study, and persistently elevated platelet count confirmed the
diagnosis of essential thrombocythemia. Essential thrombocythemia can predispose
individuals to vascular dysfunction and damage, which may contribute to coronary
artery dissection. With this case, we propose that essential thrombocythemia
should be excluded in the presence of coronary dissection and thrombocytosis.
PMID- 25845134
TI - [Codon optimization of hemagglutinin as a promising tool for improving of the
influenza vaccines immunogenicity].
AB - Modification of the codon bias of sequences is a promising tool of the gene
expression control. The theoretical basis of the codon optimization is reviewed,
data on experiments in changing the viral gene codon bias for purposes of vaccine
development are discussed. Research into the field of the influenza vaccine
immunogenicity improvement with codon optimization method is reviewed. Prospects
of the use of the codon optimization technique for influenza vaccine development
are considered.
PMID- 25845135
TI - [The ability of the natural ketones to interact with bacterial quorum sensing
systems].
AB - The effect of the natural ketones emitted by bacteria (2-nonanone, 2-heptanone, 2
undecanone) on the functioning of the Quorum Sensing (QS) systems was studied. In
this work, three lux-reporter strains containing the components of the LasI/LasR,
RhlI/RhlR, LuxI LuxR QS systems were used as biosensors for the N-acyl-homoserine
lactones. It was shown that at concentrations of ketones that exhibited little or
no bactericidal action the ketones could modulate the QS-response by suppressing
the expression of the lux-operon reporter to a greater extent than the cell
viability of these strains.
PMID- 25845136
TI - [The genome polymorphism of the Mycobacterium avium subsp. hominissuis strains].
AB - The non-tuberculosis mycobacteria Mycobacterium avium subsp. hominissuis (MAH)
are able to cause human mycobacteriosis. In this work, the results of the first
comprehensive study of the genome polymorphism of the clinical strains of MAH
were reported using the typing scheme by 13 loci MATR-VNTR (TR292, TRX3, TR25,
TR47, MATR-1, MATR-4, MATR-5, MATR-6, MATR-8, MATR-11, MATR-14, MATR-15, MATR-16)
containing tandem nucleotide sites and IS1245-RFLP-typing sites. A total of 90
MAH strains isolated from patients with lung mycobacteriosis without
epidemiological connection (including HIV infected) were tested in 2008-2011. The
inhomogeneity of the MAH strains by 36 profiles of 13 loci MATR-VNTR was
observed. The majority of the strains (68.8%) were included in the 8 MATR-VNTR
clusters; most large cluster contained 37 strains with 13-bitnumerical profile
2222223145443'. The nucleotide sequence of the MATR-16 (3') locus contains the
long deletion (GenBank accession no. KF479191). The MAH strains of the MATR-VNTR
clusters were found to be inhomogeneous by the IS1245 marker. The MATR-VNTR
typing method by 13 loci is recommended for preliminary differentiation of
domestic MAH strains with further analysis of the MATR-VNTR clusters using the
IS1245-RFLP-typing method.
PMID- 25845137
TI - [A single-tube real-time RT-PCR assay for the RNA detection and quantification of
genetically diverse HIV Including rare non-M group of the HIV-1 and HIV-2].
AB - The RT-PCR method with real-time fluorescence detection was used for development
of phi prototype of diagnostic kit for reliable diagnosis of genetic variants of
RNA of the HIV-1 of groups M, N, O, P and RNA of the HIV-2 in blood plasma and
serum. The kit is stable against nucleotide defects, provides broad linear range
of concentration of the HIV RNA, 100% analytical specificity and adequate
analytical sensitivity: 42 ME/ml (HIV-1 of group M), 45 copies/ml (HIV-2), 92
copies/ml (HIV-1 of group O), 90 copies/ml (HIV-1 of group N). The kit provided
successful detection and measurement of HIV RNA concentration in the samples of
the international reference panel of the HIV-1 genotype. The results of the test
correlate with results of commercial tests.
PMID- 25845138
TI - [Crimean-Congo hemorrhagic fever virus in Stavropol region in 2011].
AB - The genetic analysis of the Crimean-Congo hemorrhagic fever (CCHF) virus
circulating in Stavropol region during 2011 year was suggested. A total of 14 RNA
isolates from the Crimean hemorrhagic fever patients were genetically typed. The
genetic analysis of the CCHF virus stains based on M-segment sequences (positions
2607-2932) supported the circulation of the genotype Europe 1 in the Stavropol
region of Russia. In addition to previously known lineage STV-ROS, the second
lineage VLG/ROS was observed in Stavropol region.
PMID- 25845139
TI - [Molecular-genetic analysis of the genomes of porcine reproductive and
respiratory syndrome virus and porcine circovirus type 2 circulating in the area
of Russian Federation].
AB - The molecular genetic analysis of the genomes of the virus of porcine
reproductive respiratory syndrome (VPRRS) and porcine circovirus type 2 (PCV-2)
circulating in the area of the Russian Federation was discussed. The results of
this work showed the circulation of the strains of the European genotype VPRRS
similar to those found in France and Denmark from 1998 to 2001. The homology of
the fragment of one of the genes between the Russian isolates and the vaccine
strain Porcilis PRRS (Intervet) was found. It requires further study. The strains
representing the North American genotype VPRRS were not found. The PCV-2 genomes
fall into three separate goups. One (genotype 2b) is formed by isolates in
Malaysia, Brazil, Switzerland, China, Slovakia, UK, USA, isolated during the
period from 2004 to the present time. The second group consists of sequences of
the viruses isolated in 2000-2012 in Canada, the U.S., China, and South Korea
(genotype 2a). The third group is formed by highly pathogenic isolates in 2013
from China (highly pathogenic genotype 2c). The circulation of all three known
genotypes of PCV-2: 2a, 2b, and 2c in Russian Federation was demonstrated.
PMID- 25845140
TI - [Genotypic identification of the bovine leukemia virus].
AB - Phylogenetic analysis of the sequenced segments of the provirus BLV locus env
gene and the strategy of the PCR-PDRF-genotyping consistent with phylogenetic
classification of pathogenic agent and suggested in our works provided taxonomic
identification of BLV isolates identified in cattle in Tatarstan (Russian
Federation) as representatives of the 4th, 7th, and 8th BLV genotypes. Of 100
identified isolates, 64 represent the 4th BLV genotype, 28 representatives of BLV
belong to cluster of the 7th genotype, whereas the other 8 samples of the
provirus belong to the new 8th genotype of pathologic agent. The strategy VBL PCR
PDRF-genotyping suggested in our work on the basis of 5 restriction endonucleases
(PvuII, SspI, HphI, HaeIII, and BstYI) provided correct genotyping identification
of the viral pathogen.
PMID- 25845141
TI - [Prevalence of aortal atherosclerosis in workers underwent occupational
irradiation].
AB - The authors evaluated prevalence of aortal atherosclerosis in dependence on
radiation and non-radiation factors in workers underwent occupational prolonged
irradiation.The study included 22,377 workers of nuclear industry enterprise
"Mayak", with verified diagnosis of aortal atherosclerosis. Up to 31th December
2008, a total of 1,840 aortal atherosclerosis cases were registered in the
examinees group. Aortal atherosclerosis prevalence appeared to depend reliably on
sex, age, smoking habit (in males), alcohol consumption (in males) and arterial
hypertension. Findings are that aortal atherosclerosis prevalence was higher in
males and females underwent external gamma-irradiation of total dose over 0.5 Gy,
in males and females underwent internal alpha-irradiation from incorporated
plutonium of total absorbed radiation dose in liver over 0.025 Gy. Thus, aortal
atherosclerosis prevalence in workers underwent occupational irradiation de-
pended both on radiational and non-radiational factors.
PMID- 25845142
TI - [Prognostic assessment for formation of a group of cardiovascular high risk among
personnel participating in atomic submarines utilization].
AB - Ultrasound scanning of main vessels (common carotid, internal carotid, common and
superficial femoral, posterior tibial arteries) in staffers of shipyard "Nerpa"-
branch of JSC "Shipbuilding center Zvezdochka" (Snezhnogorsk city Murmansk
region)--engaged into atomic submarines utilization. Findings are atherosclerotic
changes in common carotid and common femoral arteries--increased thickness of
intima-media complex over the reference values or atherosclerotic plaque
formation. The changes were maximal in a group of males aged over 50 with length
of service over 25 years. Discriminant analysis helped to suggest a mathematic
model to forecast cardiovascular diseases in personnel of "Nerpa" shipyard.
PMID- 25845143
TI - [Medical and hygienic aspects of instrumental supervision system over nuclear
materials and radioactive substances transport on Russian Federation territory].
AB - Hygienic evaluation of radiation situation in operation of mobile and stationery
elements within a project of national system for instrumental supervision over
nuclear materials and radioactive substances transport, created with a Global
initiative against nuclear terrorism. Levels of exposure to ionizing radiation of
the screening complexes appeared to match requirements on radiation safety for
service personnel and general population.
PMID- 25845144
TI - [Evaluating psychophysiologic adaptation state in operators of Bilibino nuclear
power station].
AB - The study revealed that 60% operators of Bilibino nuclear power station suffer
from psychosomatic diseases, 41.7% of them are assigned to occupational group of
workers, and major part of the examinees with psychosomatic diseases (45.82%) are
aged 41-50, high integral level ofpsychophysiologic adaptation is revealed in 5
examinees (12.5%), medium integral level--in 12 examinees (30%). Lower integral
level of psychophysiologic adaptation manifested in decrease in psychophysiologic
and physiologic levels.
PMID- 25845145
TI - [Evaluating radiation dose load in medical personnel of radiologic diagnostic
departments].
AB - The article deals with materials on radiation hygienic evaluation of radiologic
diagnostic departments in various medical institutions of Moscow. The studies
covered work of medical staffers in X-ray examination and in contact with short
lived isotope generators. The authors outlined the examination types and stages
with maximal radiation danger. Disimetric information obtained during the study
helped to calculate values of equivalent, effective doses of radiation for
medical personnel and maximal potential doses.
PMID- 25845146
TI - [Comparative analysis of ionizing radiation and xenobiotics influence on
spermatogenic epithelium and dominant lethal mutations output in laboratory
animals].
AB - The study covered state of spermatogenic epithelium and dominant lethal mutations
output in mice of BALB/c and CBA lines, subjected to total gamma-irradiation and
in Wistar rats after intraperitoneal injection of potassium bichromate (K2Cr2,O7)
in small and sublethal doses. The BALB/c line mice under low irradiation dose
(0.25 Gy) demonstrated stimulation effect on spermatogenic epithelium, but in the
CBA line mice no such effect was seen. Both mice lines under irradiation of 0.25
Gy and 1.0 Gy demonstrated increase in pathologic sperm counts and in percentage
ofpreimplantation embryonal death. In rats, injection of potassium bichromate in
doses of 0.028 mg/kg and 2.8 mg/kg increased number of micronuclear spermatids,
larger pathologic sperm counts and percentage of postimplantation deaths. Thus,
lower general embryonal deaths under radiation exposure is due to preimplantation
embryonal deaths, under exposure to 6-valent chromium--is due to postimplantation
losses.
PMID- 25845147
TI - [Oxidative metabolism in radiation injury].
AB - The article represents results of studies concerning influence of ionizing
radiation on experimental animals under absolutely lethal doses of 8 Gy. In
single total irradiation the rats demonstrate changes in lipoperoxic cascade
products and suppressed activity of anioxidant defence enzymes in generative
cells--that causes metabolic disorders.
PMID- 25845148
TI - [Mathematic evaluation of various factor influence on functional strain in
military servicemen].
AB - The article covers mathematic assessment of factors characteristic for draft army
service on functional strain in draftees. Study objects--draftees aged 18-22
years. The studies were conducted in the beginning, in the middle and in the
endof draft army service, and in urban and rural area. The study included
physiologic and psychometry tests. Findings are that mathematic modeling cannot
remove methodic errors completely in elaborating the criteria for functional
strain, evaluation and forecasting the current performance of the draftees.
PMID- 25845149
TI - [Peculiarities of pilot's perception of flight information presented on on-board
liquid crystal displays].
AB - The article deals with results of experimental studies conducted on flight
testing desk and covering peculiarities of pilot's perception of flight
information presented on on-board liquid crystal display in dependence on changes
speed and update rate of the screen. The authors determine frequency
characteristics of information update rate, that achieve acceptable quality of
the flight parameters perception in accordance with the changes speed. Vigorous
maneuvering with high angular velocities of changed parameters of roll and pitch
causes visual distortions that are connected with poor frequency of information
update rate, deteriorate piloting quality and can cause flight unsafety.
PMID- 25845150
TI - [Study of speech characteristics in hearing-impaired pilots for creation of voice
activated system operating airborne equipment].
AB - Comparative experimental study covered speech characteristics in speakers with
normal hearing and pilot speakers with neurosensory deafness. Evaluation criteria
were duration, speech volume, spectral characteristics of words. Main difference
of speach in pilot speakers with hearing disorders was higher variability of its
characteristics.
PMID- 25845151
TI - [The autonomic system reactivity of airport technical personnel using individual
protective devices against noise].
AB - The study covered cardiac rhythm variability and hemodynamic parameters in
airfield technical personnel under exposure to aviation noise and with use of
individual protective measures against noise. Individual protective means remove
unfavorable stressful external effects of noise--that is manifested by more
stable parameters of sympathetic nervous system activity.
PMID- 25845152
TI - [Restore the connection...between physician and patient as well].
PMID- 25845154
TI - [The doctor as a neuro-shaman].
PMID- 25845155
TI - [Science and Art are they opposites?].
PMID- 25845156
TI - [The anxiogenic effect on physicians of the "less is more" approach].
PMID- 25845157
TI - [ In favor of e-cigarette].
PMID- 25845158
TI - [Against e-cigarette].
PMID- 25845160
TI - [Autohypnosis].
PMID- 25845159
TI - [How to disclose a case of dementia in office visit?].
PMID- 25845161
TI - [Deglutition disorder: what to do?].
PMID- 25845162
TI - [Neuro-otology for general practitioner].
PMID- 25845163
TI - [Anti-aging plants: plants to stay young longer].
PMID- 25845164
TI - [Psychotropic drug prescriptions in presence of comorbities].
PMID- 25845165
TI - [Last generation anti-thrombotic drugs and cerebral hemorrhage ].
PMID- 25845166
TI - [Mental competency].
PMID- 25845167
TI - [Urination disorders in neurologic patients].
PMID- 25845168
TI - [Syncope: initial diagnosis and risk stratification].
PMID- 25845169
TI - [Skull abnormalities: diagnosis and treatments].
PMID- 25845170
TI - [Botulinum toxin in neurorehabilitation-insight in current use and applications].
PMID- 25845171
TI - [Mental status: potential and limitations].
PMID- 25845172
TI - [Long-term treatment of restless leg syndrome].
PMID- 25845173
TI - [Neurological emergency in childhood].
PMID- 25845174
TI - [Posttraumatic stress disorder].
PMID- 25845175
TI - [Botulinum toxin in neurorehabilitation-insight in current use and applications].
PMID- 25845176
TI - [A physician, his patients and alcohol. Forty years of training].
PMID- 25845177
TI - [Management of HIV/ AIDS in 2015].
PMID- 25845178
TI - [Multiple sclerosis: when to think of it? How to proceed?].
PMID- 25845179
TI - [Delirium in palliative home care].
PMID- 25845180
TI - [Gastro-esophageal reflux in mentally handicapped patients].
PMID- 25845181
TI - [Endocrine causes of acute confusional state].
PMID- 25845182
TI - [Depression in aging].
PMID- 25845183
TI - [Brain food. Importance of nutrition in the prevention and treatment of
dementia].
PMID- 25845184
TI - [Psychotic disorders].
PMID- 25845185
TI - [Dizziness].
PMID- 25845186
TI - [Computed tomography--magnetic resonance tomography, what and when?].
PMID- 25845187
TI - [Parkinson disease diagnosis: not so easy...].
PMID- 25845188
TI - [Electrophysiologic exam at the service of primary care physicians].
PMID- 25845189
TI - [Statistically significant: what benefit for the patient?].
PMID- 25845190
TI - [Dying from dementia/ dying with dementia].
PMID- 25845191
TI - [Cannabis in multiple sclerosis treatment: possibilities and limits].
PMID- 25845192
TI - [Wheelchair adjustment: practical advice for the family doctor].
PMID- 25845193
TI - [The sound of Love--Neuroplasticity, singing bowls and deep relaxation for the
health of future generations].
PMID- 25845194
TI - [Muscle pain: what should you think?].
PMID- 25845195
TI - [Age related dehydroepiandrosterone decrease: clinical significance and
therapeutic interest].
AB - Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are the most abundant
steroids in humans, but their levels fall with age. This decrease has been
associated with several age related diseases such as falls, osteoporosis,
depression, atherosclerosis and sexual disorders. Moreover, studies have shown
positive effects of DHEA administration on several of these disorders, with a
satisfying safety profile. Unfortunately, DHEA has been too frequently mediatized
as a "fountain of youths, which was responsible for either inadequate
prescription, or prescription refusal. Longer studies in large populations should
help to better define indications, treatment modalities and long-term treatment
safety.
PMID- 25845196
TI - [Cystic fibrosis: fifty years of progress. And now what?].
PMID- 25845197
TI - [Confusion].
PMID- 25845198
TI - [Cancers explained by "bad luck": a growing controversy].
PMID- 25845199
TI - [What key words to use to retrieve pertinent articles?].
PMID- 25845200
TI - [The case of the obscene mural in Clermont-Ferrand university hospital
residents'room].
PMID- 25845201
TI - [Neuchatel's hospitals: the government says "stop"].
PMID- 25845202
TI - [Yasmin pill: federal tribunal rules against the plaintiff].
PMID- 25845203
TI - [The error in health].
PMID- 25845204
TI - Synthetic biology and biosecurity.
AB - This article discusses the conflict fields and legal questions of synthetic
biology, esp. concerning biosecurity. A respective jurisprudential discussion has
not taken place yet in Germany apart from few statements and recommendations. But
in Germany, Europe and the USA, it is generally accepted that a broad discussion
is necessary. This is esp. true for the question of biosecurity and the possible
dangers arising from Synthetic Biology.
PMID- 25845205
TI - [Patents and scientific research: an ethical-legal approach].
AB - This article aims to review the relationship between patents and scientific
research from an ethical point of view. The recent developments in the law of
industrial property led in many cases to patent discoveries, contributions of
basic science, and laws of nature. This trend, which denies the central
principles of the discipline, creates disturbances in scientific activity, which
requires the free movement of knowledge in order to develop their potentialities.
PMID- 25845206
TI - Governing synthetic biology in the light of the Access and Benefit Sharing
regulation (ABS).
AB - Synthetic biology is a change of paradigm, i.e. from the exploitation of natural
and genetic resources to lab production of biological entities. This transitional
shift represents a great challenge for developing countries, particularly those
which host biodiversity, and users of genetic resources, since the latter might
not be longer required to access to actual genetic resources (tangible genetic
resources) but rather genetic resources' information (intangible genetic
resources) in order to replicate those resources in labs. This could mean that
users of genetic resource would not have to comply with the Convention on
Biological Diversity (CBD) and its complementary treaty, the Nagoya Protocol,
known also as the Access and Benefit Sharing regime (ABS). Both international
instrument demands that States create legal mechanisms to secure access and
benefit sharing, i.e., users of genetic resources are required to obtain prior
informed consent (PIC) from host countries of biodiversity and reach mutual
agreed terms (MATs), in which users and countries agree how to share the benefits
arise from the utilization of genetic resources. The ABS regime is particularly
relevant since its implementation at national and regional level has created
tensions between users of genetic resources and developing countries. This
situation could lead to users removing interest in the exploitation of genetic
resources, subsequently, meaning that their focus would move towards technologies
that rely less on tangible genetic resources, including synthetic biology. This
papers aim to discuss the scope of the CBD and the Nagoya Protocol in the light
of synthetic biology and the implications for developing countries.
PMID- 25845207
TI - The legal fate of biobanks between privacy, IPRs and crisis of a firm. A
preliminary study on the case of "bio-bankruptcy" .
AB - In the case of biobank bankruptcy, the current legal framework is not suitable to
protect the rights of research subjects. In the paper we identify such a gap in
protection and suggest some remedies to address it.
PMID- 25845208
TI - Genetic resources, biotech patents and gene ownership.
AB - Human genetic resources are increasingly considered as ordinary commercial goods,
but their value and utility go beyond the simple and immediate private profit. In
contrast to other biological resources, commercial use does not focus upon the
material itself but rather upon the genetic information it contains. Information
goods are then usually subject to intellectual property rights, but in the
biological and life science domains, property rights can have a negative
influence upon the proper allocation of several goods, including genetic material
or goods that are related to it. This scenario reflects the facts of recent
litigations in the United States and Europe. In particular, these lawsuits have
revived the debate over private ownership and control over genes. Within this
context, the objective of the paper is to discuss how to recast the traditional
right to access to and use of biochemical and human genetic material currently
considered as part of the market framework. Looking beyond the protection of
traditional public goods, the paper emphasizes the debate around the progressive
commodification of human genetic resources facilitated by an improper use of
intellectual property rights. Different scenarios are analyzed to evaluate
alternative instruments and new regulatory approaches to avoid the private
appropriation of human genetic resources and other natural assets.
PMID- 25845209
TI - [Impact of synthetic biology on patent law in view of of European jurisprudence].
AB - The roots of synthetic biology--the redesign of biological molecules, structures
and organisms--can be traced to the research developed by Jacques L. Monod and
Francois Jacob in 1961. This field has undergone significant growth in the past
ten years and its emergence has raised the question of whether the patent system
is suitable to protect inventions in emergent areas as synthetic biology. The
article will analyze the numerous scientific, socio-economic, ethical and legal
challenges faced by synthetic biology, introducing the European Patent Law
related to biotechnology as the minimum common framework and considering if more
changes are needed to adequately protect the inventor rights, while taking into
account the arrival of a new research culture, characterized by embracing open
innovation and open-source initiatives. The discussion will review some
biotechnological patent law cases and summarize questions as whether isolated
molecules of DNA are eligible for patent or the patentability of living matter,
under the terms of Directive 98/44/EC. The article will finally consider the
impact of synthetic biology on the European patent system.
PMID- 25845210
TI - [How to be prudent with synthetic biology. Synthetic Biology and the
precautionary principle].
AB - Synthetic biology is a new discipline that is twofold: firstly it offers the
promise to pay benefits that can alleviate some of the ills that plague mankind;
On the other hand, like all technologies, holds risks. Given these, the most
critical and concerned about the risks, invoke the application of the
precautionary principle, common in cases where an activity or new technology
creates risks to the environment and/or human health, but far from universally
accepted happens to be currently one of the most controversial principles. In
this paper the question of the risks and benefits of synthetic biology and the
relevance of applying the precautionary principle are analyzed. To do this we
proceed as follows. The first part focuses on synthetic biology. At first, this
discipline is characterized, with special attention to what is novel compared to
the known as "genetic engineering". In the second stage both the benefits and the
risks associated with it are discussed. The first part concludes with a review of
the efforts currently being made to control or minimize the risks. The second
part aims to analyze the precautionary principle and its possible relevance to
the case of Synthetic Biology. At first, the different versions and
interpretations of the principle and the various criticisms of which has been the
subject are reviewed. Finally, after discarding the Precautionary Principle as an
useful tool, it is seen as more appropriate some recent proposals to treat
technologies that take into account not only risks but also their benefits.
PMID- 25845211
TI - [Law 4/2014, of December 9, amending Law 7/2003 of 20 October, by which research
in Andalusia with non-viable human pre-embryos for in vitro research is
regulated, and amending Law 1/ 2007 of 16 March, by which research in cellular
reprogramming is regulated exclusively for therapeutic ends].
PMID- 25845212
TI - [Effect of electroacupuncture stimulation of "Housanli" (ST 36) and "Zhongwan"
(CV 12) on serum leptin and hepatocellular JAK 2-STAT 3 signaling in obese rats].
AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
"Housanli" (ST 36) and "Zhongwan" (CV 12) on serum leptin level and expression of
phosphorylated Janus kinase 2 (p-JAK 2) and phosphorylated signal transducer and
activator of transcription 3 (p-STAT 3) proteins in the liver tissue of obese
rats. METHODS: Thirty-two male Wistar rats were randomly divided into control
group, model group, manual acupuncture (MA) group and EA group (n = 8 in each
group). The obese model was induced by high fat diet for 8 weeks. MA or EA (20
Hz, 1.5 V) stimulation was applied to bilateral "Housanli" (ST 36) and "Zhongwan"
(CV 12) for 20 min, once daily for 4 weeks. The animals' body weight and length
were recorded, and Lee's index was calculated. Serum leptin level and liver p-JAK
2 and p-STAT 3 protein expression levels were detected using radioimmunoassay and
Western blot, respectively. RESULTS: In comparison with the control group, the
rats' body weight, Lee's index, and serum leptin content were remarkably
increased in the model group (P<0.05), while hepatocellular p-JAK 2 and p-STAT 3
protein expression levels were significantly down-regulated in the model group
(P<0.05). After treatment for 4 weeks, the levels of body weight, Lee's index,
serum leptin were significantly reduced (P<0.05), and hepatocellular p-JAK 2 and
p-STAT 3 protein expression in the MA and EA groups were considerably up
regulated compared with the model group (P<0.05). The effect of EA was apparently
superior to that of MA in up-regulating p-JAK 2 and p-STAT 3 protein expression
(P<0.05). CONCLUSION: Both EA and MA stimulation can reduce the obese rats' body
weight, and Lee's index, which may be closely associated with their effects in
down-regulating serum leptin and in enhancing hepatocellular p-JAK 2 and p-STAT 3
protein expression.
PMID- 25845213
TI - [Effects of scalp-acupuncture on astrocyte apoptosis in hippocampal CA 1 region
in rats with vascular dementia].
AB - OBJECTIVE: To observe the effect of scalp-acupuncture intervention on the
expression of Bcl-2 of astrocytes in the hippocampus in vascular dementia (VD)
rats, so as to reveal its underlying mechanism in improving VD. METHODS: A total
of 40 male SD rats were randomly divided into normal control, sham-operation, VD
model, and scalp-acupuncture groups (n=10 in each group). The VD model was
established by using modified Pulsinelli 4-vessel-occlusion method. Scalp
acupuncture was applied to bilateral "Daozang Shangjiao" and bilateral "Jiyi",
and "Siwei" acupoints according to FANG's scalp-acupuncture therapy for 30 min,
once daily for 10 days. The rat's learning-memory ability was detected by Morris
water maze tests, and the expression of apoptosis related proteins Bcl-2 of
astrocytes in the hippocampus was detected by immunofluorescence double labeling
technique and Western blot, respectively. RESULTS: Morris water maze tests showed
that the average escape latency of place navigation test and the duration of the
first platform-site crossover (space probing test) were significantly increased
in the model group compared with the normal control group (P<0.01), and the
number of platform-site crossovers in 2 min was markedly decreased in the model
group (P<0.01). The increased average escape latency and the increased duration
of first platform-site crossover were markedly shortened in the scalp-acupuncture
group in comparison with the model group (P<0.01), and the number of the platform
crossovers in 2 min was significantly increased in the scalp-acupuncture group
(P<0.01). The expression of Bcl-2 protein and the number of GFAP/Bcl-2-labeled
cells of hippocampal CA 1 region in the model group were remarkably decreased
compared with the normal control group (P<0.01). After scalp-acupuncture
intervention, the decreased Bcl-2 protein expression level and the number of
double-labeled GFAP/Bcl-2 cells were significantly up-regulated in the scalp
acupuncture group compared with the model group (P<0.01). No significant
differences were found between the normal control and sham-operation groups in
the escape latency, duration of the first platform-site crossover, number of
platform crossovers in 2 min, number of GFAP/Bcl-2 double labeled cells and the
expression level of hippocampal Bcl-2 protein (P>0.05). CONCLUSION: Scalp
acupuncture can effectively regulate the expression of apoptosis related proteins
Bcl-2 of astrocytes in the CA 1 region of hippocampus in rats with VD, which may
contribute to its effect in the improvement of VD.
PMID- 25845214
TI - [Effect of electroacupuncture intervention on expression of testicular P 450
scc/17 beta-HSD3 in rats with partial androgen deficiency].
AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on
expression of cytochrome P 450 side chain cleavage (P 450 scc) and 17 beta
hydroxysteroid dehydrogenase 3 (17 beta-HSD3) in the testis in partial androgen
deficiency of aging male (PADAM) rats so as to reveal its mechanism underlying
improving PADAM. METHODS: Thirty male SD rats were randomly and equally divided
into control, model, and EA groups. The PADAM model was established by
intraperitoneal injection of cyclophosphamide (20 mg . kg(-1) . d(-1)), once
daily for 5 days. EA (20-30 Hz, 1-3 mA) was applied to bilateral "Shenshu" (BL
23) and "Guanyuan" (CV 4) for 15 min, once daily for 8 weeks. Serum total
testosterone (TT) and free testosterone (FT) levels were measured using enzyme
linked immunosorbent assay (ELISA). The expression levels of P 450 scc/17 beta
HSD3 proteins and mRNA in the testis tissue were assayed by immunohistochemistry,
Western bolt (WB) and RT-polymerase chain reaction (RT-PCR), separately. RESULTS:
Compared with the control group, both serum TT, FT levels and expression levels
of P450 scc/17 beta-HSD3 proteins and mRNA in the testis tissue in the model
group were significantly down-regulated (P<0.01). After EA intervention, compared
with the model group, the cyclophosphamide-induced decrease of serum TT, FT
levels and the expression levels of P 450 scc/17 beta-HSD3 proteins and mRNA in
the testis was reversed in the EA group (P<0.01). CONCLUSION: EA intervention is
effective in up-regulating serum TT and FT, testicular P 450 scc and 17 beta-HSD3
proteins and mRNA levels in PADAM rats, which may be one of its mechanisms
underlying improvement of PADAM.
PMID- 25845215
TI - [Effects of Zhuang-medical thread moxibustion combined with needle-pricking on
vascular oxidative stress injury in the rat].
AB - OBJECTIVE: To observe the effect of Zhuang-medical thread moxibustion combined
with needle-pricking on vascular oxidative stress injury in oxidative stress
injury rats. METHODS: Eighty Wistar rats were randomly allocated to normal
control, sham operation (sham), model, and combined treatment groups (n=20 in
each group). The oxidative stress injury model was established by ligation of the
left sciatic nerve to induce chronic constriction injury (CCI) pain stress
stimulation. Zhuang-medical thread moxibustion was applied to bilateral "Zusanli"
(ST 36), once a day for 3 weeks. Needle-pricking was applied to left
"Yanglingquan" (GB 34) and left "Huantiao" (GB 30), once a day for 3 weeks except
Sundays. Plasma 6-keto-PGF 1alpha, thromboxane B 2 (TXB 2), NO and ET contents
were assayed by radioimmunoassay. COX-2 immunoactivity of the femoral artery was
determined by immunohistochemistry, and pathological changes of the femoral
artery were detected by H. E. staining. RESULTS: Compared with the control group,
the levels of plasma 6-keto-PGF 1alpha and NO in the model group were
significantly reduced (P<0.05), while those of plasma TXB 2 and ET and COX-2
expression in the femoral artery were obviously increased in the model group
(P<0.01). After moxibustion plus needle-pricking treatment, CCI-induced decrease
of plasma 6-keto-PGF 1alpha and NO contents, and increase of plasma TXB 2 and ET
and COX-2 expression levels were obviously reversed (P<0.05, P<0.01). The tubal
wall of the femoral artery in rats of the model group got thicker, while that of
the combined treatment group was relatively thinner, suggesting an inhibition of
vascular intimal hyperplasia after the treatment. CONCLUSION: Zhuang-medical
thread moxibustion combined with needle-pricking of ST 36, GB 34 and GB 30 can
reduce the expression of femoral artery COX-2 and regulate the balance of both
plasma PGI 2/TXA 2 and plasma NO/ET in CCI-induced oxidative stress rats, which
may contribute to its effect in suppressing oxidative stress-induced vascular
intimal hyperplasia.
PMID- 25845216
TI - [Effects of electroacupuncture on learning-memory ability and expression of
hippocampal vascular endothelial growth factor (VEGF), VEGF receptor 1 and 2
genes in vascular cognitive impairment rats].
AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Dazhui" (GV 14),
"Baihui" (GV 20), etc. on learning-memory ability and expression of vascular
endothelial growth factor (VEGF) mRNA, VEGF receptor 1 (VEGFR-1/Flt-1) mRNA, and
VEGFR-2 (Flk-1) mRNA in the hippocampus in vascular cognitive impairment (VCI)
rats so as to reveal its mechanism underlying improvement of VCI. METHODS: A
total of 60 Wistar rats were randomly divided into sham operation, VCI model, EA
and medication groups (n=12 in each group). The VCI model was established by
occlusion of the bilateral vertebral arteries and bilateral cervical arteries. EA
(2 Hz/20 Hz) was applied to "Baihui" (GV 20), "Dazhui" (GV 14), "Shuigou" (GV 26)
and "Shenting" (GV 24) for 20 min, once daily for 20 days. Rats of the medication
group were treated by intragastric perfusion of Aniracetam capsules (0.0625
g/kg),once daily for 20 days. The rats' learning-memory ability was detected by
step-down test. The expression levels of VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA in
the hippocampus were detected by RT-PCR, and the neurological deficit scores were
assessed by Zea Longa (0-4 scaling) method. RESULTS: Compared with the sham
operation group, rats of the model group showed a significant increase in
reaction time and error number and decrease of escape latency (reduction of
learning-memory ability), and increase in neurological deficit score, and in
expression levels of hippocampal VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA (all
P<0.01). After EA treatment, in comparison with the model group, the learning
memory ability and hippocampal VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA were
apparently increased, neurological deficit score were markedly decreased in the
EA group (all P<0.01). The effects of EA treatment was obviously superior to
those of medication in raising learning-memory ability and up-regulating
hippocampal VEGF mRNA and Flt-1 mRNA expression levels, and in reducing
neurological deficit score (all P<0.05). CONCLUSION: EA intervention can
apparently up-regulate hippocampal VEGF mRNA, Flt-1 mRNA and Flk-1 mRNA
expression in VCI rats, which may contribute to its effect in improving learning
memory ability, possibly by promoting neovasculization.
PMID- 25845217
TI - [Effect of electroacupuncture stimulation of "Baihui" (GV 20) and " Yongquan" (KI
1) on expression of hippocampal amyloid-beta and low density lipoprotein receptor
related protein-1 in APP/PS 1 transgenic mice].
AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) treatment on the
level of hippocampal amyloid-beta peptide (Abeta) and its key transport receptor
low density lipoprotein receptor-related protein-1 (LRP 1) in APP/PS 1 transgenic
mice so as to explore its mechanism underlying improvement of Alzheimer's disease
(AD). METHODS: Twenty-four male APP/PS 1 transgenic mice were equally and
randomly divided into model group and EA treatment group, and 12 C 57 BL/6 mice
were used as the normal control group. EA (1 Hz/50 Hz, 0.3 mA) was applied to
"Baihui" (GV 20) and "Yongquan" (KI 1) for 15 min, once every other day for 6
weeks. The learning-memory ability was detected by using Morris water maze
testing, left hippocampal Abeta 1-40 and Abeta 1-42 contents were assayed by
ELISA, and right hippocampal LRP 1 expression was detected using Western blot
(WB). RESULTS: Results of Morris water maze test showed no significant
differences among the three groups in the escape latency, the times of the
platform-site crossovers, the time spent in the target platform quadrant
(P>0.05). Compared with the model group, the moderately increased escape latency
had a decreasing tendency in the EA treatment group. ELISA assaying showed that
hippocampal Abeta 1-42, Abeta 1-40, and ratio of Abeta 1-42/Abeta 1-40 of the
model group were significantly higher than those of the normal control group
(P<0.01). After EA intervention, the increased Abeta 1-42 , Abeta 1-40, and ratio
of Abeta 1-42/Abeta 1-40 were remarkably down-regulated in the EA treatment group
(P<0.01). WB detection displayed that the right hippocampal LRP 1 expression
level of the model group was markedly lower than that of the normal control group
(P<0.05). After EA treatment, LRP 1 expression level was moderately up-regulated
but without significant difference between the model and EA treatment groups
(P>0.05). CONCLUSION: EA intervention can lower the level of hippocampal Abeta in
APP/PS 1 transgenic mice, but its effects on Abeta transport receptor LRP 1
expression and learning-memory ability need being confirmed further.
PMID- 25845218
TI - [Effect of electroacupuncture of "Xiaohai" (SI 8) and "Xiajuxu" (ST 39) on serum
TNF-alpha and duodenal high mobility group protein B 1 levels in duodenal ulcer
rats].
AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
"Xiaohai" (SI 8) and "Xiajuxu" (ST 39) on serum TNF-alpha and duodenal high
mobility group protein B 1 (HMGB 1) levels in rats with duodenal ulcer (DU), so
as to analyze its underlying mechanism in improving DU. METHODS: Forty SD rats
were randomly divided into normal control, model, Xiaohai (SI 8) and Xiajuxu (ST
39) groups (n=10 in each group). The DU model was established by intramuscular
injection of 10% Cysteamine hydrochloride (300 mg/kg), followed by taking water
containing 1% Cysteamine hydrochloride for 48 h. EA (10 Hz/50 Hz, 1-3 mA) was
applied to bilateral SI 8 and ST 39 for 30 min, once a day for 10 days. The DU
score (0-5 score) was evaluated according to Moraes' method. Serum TNF-alpha
content was determined by ELISA and duodenal HMGB 1 expression was measured by
immunohistochemistry. RESULTS: Compared to the normal control group, the DU
score, serum TNF-alpha content, and duodenal HMGB 1 expression level of the model
group were significantly higher (P<0.01). Following EA intervention, the
increased DU score, serum TNF-alpha content, and duodenal HMGB 1 expression level
were considerably down-regulated in the two EA groups in comparison with the
model group (P<0.01, P<0.05) except HMGB 1 in the SI 8 group (P>0.05), and the
effect of EA of "Xiajuxu" (ST 39), the lower-He point, was remarkably superior to
that of "Xiaohai" (SI 8) in reducing DU score and TNF-alpha content (P<0.01).
CONCLUSION: EA stimulation of SI 8 and ST 39 can improve duodenal ulceration in
DU rats, which may be related to its effect in down-regulating serum TNF-alpha
and duodenal HMGB 1 expression. The therapeutic effect of ST 39 is markedly
better than SI 8 in relieving duodenal ulceration.
PMID- 25845219
TI - [The impact of different duration of EA-pretreatment on expression of MMP-9 and
VEGF in blood-brain barrier in rats with cerebral ischemia-reperfusion injury].
AB - OBJECTIVE: To observe the impact of preconditioning of EA stimulation of "Baihui"
(GV 20) and "Shuigou" (GV 26) in different duration on expression of matrix
metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) in blood
brain barrier (BBB) tissues in rats with cerebral ischemia-reperfusion injury
(CI/RI). METHODS: Sixty-four male SD rats were randomly allocated to sham
operation (sham), model, EA-pretreatment 7 days (pre-t-7 d) and EA-pre-t-15 d
groups (16 rats/group, 8 rats for immunohistochemistry and 8 for RT-PCR). The
CI/RI model was established by occlusion of the middle cerebral artery for 90 min
and reperfusion. EA (2 Hz/15 Hz, 1 mA) was applied to GV 20 and GV 26 for 30 min,
once daily for 7 days and 15 days respectively before modeling.
Immunohistochemical staining and fluorescence quantitative RT-PCR were employed
to detect the expression of MMP-9 protein, MMP-9 mRNA and VEGF mRNA in the BBB
tissues (choroid plexus). RESULTS: Compared with the sham group, the number of
MMP-9 immuno-reaction positive cells, and the expression of MMP-9 mRNA and VEGF
mRNA in the model group were significantly increased (P<0.001), while compared
with the model group, the number of MMP-9 positive cells, and expression levels
of MMP-9 mRNA and VEGF mRNA in the EA-pre-t-7 d and EA-pre-t-15 d groups were
significantly reduced (P<0.01), and the effects of EA-pre-t-15 d were markedly
superior to those of EA-pre-t-7 d (P<0.01, P<0.05). CONCLUSION: EA-pretreatment
of GV 20 and GV 26 can effectively restrain CI/RI-induced increase of expression
of MMP-9 protein, MMP-9 mRNA and VEGF mRNA in blood-brain barrier in CI/RI rats,
which may contribute to its protective effect of ischemic cerebral tissue. Longer
EA-pretreatment is relatively better.
PMID- 25845220
TI - [Effect of electroacupuncture stimulation of "Neiguan" (PC 6) on expression of
alpha- and beta-subunit proteins of voltage-gated sodium channels in rats with
myocardial ischemia].
AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
"Neiguan" (PC 6) on expression of sodium (Nav) channel alpha-subunit 1.5 and Nav
beta-subunits beta 1-beta 4 (the known myocardial sodium channel proteins) in
acute myocardial ischemia (AMI) rats so as to explore its mechanisms underlying
protection of ischemic myocardium. METHODS: Sixty SD male rats were randomly
divided into normal control, AMI model, Neiguan (PC 6), Lieque (LU 7) and non
acupoint groups. The AMI model was established by intravenous injection of
Isoprenaline (85 mg/kg) once daily for 2 days. Myocardial Nav 1.5 and Nav beta 1,
beta 2, beta 3, beta 4 protein expression levels were detected by Western blot.
RESULTS: In comparison with the control group, myocardial Nav 1.5, beta 1, beta
2, beta 3 and beta 4 protein expression levels were significantly down-regulated
in the AMI model group (P<0.01). After EA stimulation, compared with the model
group, the expression levels of Nav 1.5, Nav beta 1, beta 2, beta 3 and beta 4
protein expression levels were significantly up-regulated in the Neiguang (PC 6)
and Lieque (LU 7) groups (P<0.01) rather than in the non-acupoint group (P>0.05).
There was no statistical significance between the Neiguan (PC 6) and Lieque (LU
7) groups in beta 4 protein expression level (P>0.05). CONCLUSION: EA stimulation
of both PC 6 and LU 7 can significantly reverse AMI-induced down-regulation of
myocardial Nav 1.5, beta 1, beta 2, beta 3 and beta 4 protein expression levels
in AMI rats, which might contribute to its function in improving AMI by reducing
calcium overload.
PMID- 25845221
TI - [The effect of acupuncture stimulation of Ashi-point on hepatocyte growth factor
expression in the soft tissue in acute contusion rats].
AB - OBJECTIVE: To observe the effect of acupuncture stimulation of Ashi-point on
hepatocyte growth factor (HGF) protein expression in gastrocnemius muscle (GM) in
rats with traumatic injury of GM, so as to reveal its mechanism underlying
improvement of traumatic injury of skeletal muscle. METHODS: A total of 80 SD
rats were randomly divided into normal control (n = 8), model, acupuncture
control, and acupuncture treatment groups, and the latter 3 groups were further
allocated to 0 h, 24 h and 48 h subgroups (n = 8 in each subgroup). The acute
soft tissue contusion model was established by using 500 g-counterweight free
falling hitting at the GM of the right leg (height 30 cm). The Ashi-point was
punctured with a piece of filiform needle by penetrating the site beside the
injured GM, and stimulated for about 5 seconds. For acupuncture control group,
acupuncture was performed in the same Ashi-point in normal rats. Pathological
changes of the focal GM were observed by H. E. staining and HGF protein
expression of GM was detected by Western blot. RESULTS: H.E. staining showed that
different degrees of injury of GM tissue including broken muscle fibers with
cellular swelling, inflammatory cell infiltration, muscle fibrinolysis, atrophy,
degeneration and necrosis, etc., were found at each time-point after modeling,
while in the acupuncture treatment group, the severity of muscle injury was
relatively milder particularly at the time-points of 24 h and 48 h. Compared with
the normal control group, HGF protein expression levels of GM at the 3 time
points in the model group, and at 48 h in the acupuncture control group were
markedly increased (P<0.05, P<0.01); while in comparison with the model group,
HGF protein expression levels were remarkably down-regulated at 24 h and 48 h
after acupuncture treatment (P<0.01, P<0.05). CONCLUSION: Acupuncture stimulation
of Ashi-point can significantly down-regulate HGF protein expression in the GM in
soft tissue contusion rats, which may contribute to its effects in relieving
contusion injury of skeletal muscle.
PMID- 25845222
TI - [Acupoint injection of kakkonein for early- or mid-stage Parkinson's disease: a
multicenter randomized controlled clinical trial].
AB - OBJECTIVE: To investigate short- and long-term benefits and safety of acupoint
injection of kakkonein for early- or mid-stage Parkinson's disease (PD). METHODS:
A total of 135 patients with early- or mid-stage PD were enlisted and 116 cases
completed the observation, including 40 cases in the acupoint-injection group, 37
cases in the acupuncture group and 39 cases in the medication group. Patients of
the acupoint-injection group were treated by injection of kakkonein (2 mL) into
bilateral Fengchi (GB 20), once very other day for 8 weeks. For acupuncture
intervention, bilateral GB 20 acupoints were punctured with filiform needles,
once every other day for 8 weeks. Patients of the medication group were treated
by oral administration of compound levodopa (125 mg/time, twice a day) for 8
weeks. The disease severity was assessed by using Unified Parkinson's Disease
Rating Scale (UPDRS, version 3. 0) before and after treatment, and one month
after the treatment. RESULTS: After the treatment, scores of psychosis, behavior
and emotion, daily life activity and motor function were all significantly
decreased in the three groups in comparison with pre-treatment in each group
(P<0.05), suggesting an improvement of the PD patients' conditions. The
therapeutic effect of acupoint-injection and acupuncture groups was markedly
superior to that of the medication group (P<0.05). One-month's follow-up showed
that the scores of behavior-emotion and daily life activity were obviously lower
in the acupoint-injection group than in the acupuncture and medication groups
(P<0.05). No significant differences were found between the acupuncture and
medication groups in down-regulating scores of behavior-emotion, daily life
activity and motor function (P>0.05). CONCLUSION: Acupoint injection of kakkonein
can improve patients' behavior, emotion, and daily life activity in early- or mid
stage PD patients and has both short- and longer-term benefits.
PMID- 25845223
TI - [Clinical trials for treatment of primary hyperlipidemia by using acupuncture in
combination with Lipitor].
AB - OBJECTIVE: To observe the clinical effect of acupuncture therapy combined with
Lipitor in the treatment of primary hyperlipidemia (spleen deficiency and food
stagnation type). METHODS: Sixty primary hyperlipidemia patients (spleen
deficiency and food stagnation type) were equally randomized into medication
group and acupuncture plus medication group. Patients of both groups were treated
by oral administration of Lipitor (20 mg/tablet, one tablet per day) for 6 weeks.
Manual acupuncture stimulation was applied to Baihui (GV 20), Zhongwan (CV 12),
and bilateral Zusanli (ST 36), Sanyinjiao (SP 6), Yin-lingquan (SP 9) and
Fenglong (ST 40) for 40 min, twice daily for 6 weeks except the weekends. Serum
total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol
(HDL-C), low density lipoprotein-cholesterol (LDL-C) were detected by using a
full-automatic biochemistry analyzer before and after the treatment. The
therapeutic effect was assessed according to the standards described in "Guide
Principles for Clinical Researches of New Chinese Herbal Drugs". RESULTS: After
the treatment, the levels of serum TC, TG of the two groups were significantly
decreased in comparison with pre-treatment in the same one group (P<0.05), and
the therapeutic effect of the acupuncture+medication group was significantly
superior to that of simple medication group in lowering serum TC, TG and LDL-C
levels and heightening HDL-C levels (P<0.05). Of the two 30 cases in the
medication and acupuncture+medication groups, 2 (6.7%) and 7 (23.3%) were
basically controlled in their blood-lipid levels, 10 (33.3%) and 15 (50.0%) had a
marked improvement, 10 (33.3%) and 6 (20.0%) were improved, and 8 (26.7%) and 2
(6.7%) were invalid, with the effective rates being 73.3% and 93.3%,
respectively. CONCLUSION: Acupuncture combined with administration of Lipitor is
effective in improving primary hyperlipidemia in patients, which is superior to
administration of simple Lipitor.
PMID- 25845224
TI - [Comparison of therapeutic effects between acupoint-injection and intramuscular
injection of Bacillus Calmette-Guerin polysaccharide nucleic acid for bronchial
asthma].
AB - OBJECTIVE: To observe the curative effect of acupoint-injection and intramuscular
injection of Bacillus Calmette-Guerin (BCG) Polysaccharide Nucleic Acid for
bronchial asthma. METHODS: Sixty patients with bronchial asthma were equally
randomized into acupoint-injection group and intramuscular-injection group. For
patients of the acupoint-injection group, 2 mL of BCG was injected into bilateral
Feishu (BL 13, 1 mL for one side) once per day in the first 15 days, and once
every other day in the rest 2.5 months except weekends. Intramuscular-injection
was conducted at the lateral sites of the left or right buttock, 2 mL/time for
each site, and the injection frequency was the same to that of the acupoint
injection. The therapeutic effect was assessed according to the standards of
Guide Principles for Clinical Research of New Chinese Herbal Drugs (2002) and
Asthma Group of Breathing Diseases of China Medical Association (2008). Changes
of FEV 1 (forced expiratory volume in the first second)/FVC (forced vital
capacity) and PEF% (peak expiratory flow) were detected using a pulmonary
function detector. Serum IgA, IgM, IgG and IgE contents were assayed by using an
autonomic biochemical analyzer. RESULTS: After 3 months' treatment, the scores of
patients' symptoms and signs and serum IgE and IgG levels were significantly
decreased in both muscular-injection and acupoint-injection groups (P<0.01),
while asthma controlled test (ACT) scores FEV 1/FVC% and PEF% values were
considerably increased in both groups compared to pre-treatment in the same one
group (P<0.01). The effects of acupoint-injection were markedly superior to those
of the intramuscular-injection in reducing clinical symptom-sign score, and serum
IgE content, and in up-regulating ACT score, FEV 1/FVC% and PEF% levels (P<0.05,
P<0.01). There were no significant differences in serum IgG, IgA and IgM levels
between the two groups 3 months following the treatment (P>0.05). CONCLUSION:
Acupoint-injection of BCG polysaccharide nucleic acid can effectively improve
bronchial asthma patients' clinical symptoms and sings and pulmonary function,
which may be closely associated with its function in down-regulating serum IgE
and IgG levels.
PMID- 25845225
TI - [Body acupuncture combined with auricular acupressure for menstrual headache: a
randomized controlled clinical trial].
AB - OBJECTIVE: To observe the therapeutic effect of body acupuncture combined with
auricular acupressure for treatment of menstrual headache of hyperactivity of
"liver fire". METHODS: A total of 85 menstrual headache patients with
hyperactivity of "liver-fire" were randomly divided into control group (n = 42)
and treatment group (n = 43). Patients of the control group were treated by oral
administration of Flunarizine Hydrochloride Capsules (Sibelium, 5 mg/time, twice
daily) for 5 days beginning at the headache attack in the first menstrual cycle,
and for two weeks (except weekends) in the second and third menstrual cycles.
Patients of the treatment group were treated by manual acupuncture stimulation of
body acupoints Baihui (GV 20), Fengchi (GB 20), Sanyinjiao (SP 6), Taichong (LR
3), Xiaxi (GB 43), Taiyang (EX-HN 5), Hanyan (GB 4), Xuanlu (GB 5) and Shuaigu
(GB 8) beginning from the headache attack, and otopoint-pellet pressure of
otopoints unilateral Endocrine, Ovaries, Shenmen, Cortex, Liver, Spleen and
Kidney (beginning 5 days before menstrual onset) and bilateral Shenmen, Nie,
Liver, Gallbladder, Subcortex and Jiaogan during headache attack. Clinical
symptom scores were assessed according to the "Guiding Principles for Clinical
Research on New Chinese Herbal Drugs" issued by the Chinese Ministry of Health.
RESULTS: After the treatment, of the 42 and 43 cases in the control and treatment
groups, 9 (21.43%) and 20 (46.51%) were cured, 12 (28.57%) and 14 (32.56%) had a
marked improvement, 13 (30.95%) and 7 (16.28%) were effective, 8 (19.05%) and 2
(4.65%) invalid, with the effective rates being 80.95% and 95.35% , respectively.
The curative effect of the treatment group was significantly better than that of
the control group (P<0.05). The symptom score and VAS score after the treatment
and 3 months post-treatment in the treatment group were significantly lower than
those of the control group (P<0.01). The headache scores and VAS scores were
significantly reduced following the treatment and 3 months after the treatment in
both control and treatment groups (P<0.01). After the treatment for 2-3
therapeutic courses, the headache attack duration during menstruation was
markedly and gradually shortened in both groups (P<0.01), and therapeutic effect
of the treatment group was significantly better than that of the control group
(P<0.01). CONCLUSION: Body acupuncture combined with auricular acupressure
treatment can effectively relieve menstrual headache in menstrual women with
hyperactivity of "liver fire".
PMID- 25845226
TI - [Design and establishment of modern literature database about acupuncture Deqi].
AB - A search on acupuncture Deqi was conducted using four Chinese-language biomedical
databases (CNKI, Wan-Fang, VIP and CBM) and PubMed database and using keywords
"Deqi" or "needle sensation" "needling feeling" "needle feel" "obtaining qi",
etc. Then, a "Modern Literature Database for Acupuncture Deqi" was established by
employing Microsoft SQL Server 2005 Express Edition, introducing the contents,
data types, information structure and logic constraint of the system table
fields. From this Database, detailed inquiries about general information of
clinical trials, acupuncturists' experience, ancient medical works, comprehensive
literature, etc. can be obtained. The present databank lays a foundation for
subsequent evaluation of literature quality about Deqi and data mining of
undetected Deqi knowledge.
PMID- 25845227
TI - [Mast cell-derived exosome participates in acupoint-stimulation initiated local
network activities].
AB - The exosome, released from mast cells, T cells, B cells and many other types of
cells, is the common form of vesicle transportation between cells and
participates in the exchange of information between cells, and may be also
involved in acupuncture induced clinical effects. In the present paper, the
authors reviewed recent development of researches on this field from 1)
acupuncture stimulation induces changes of number and function of mast cells in
the local acupoint area, probably being the key factor for initiating acupuncture
effect; 2) acupuncture stimulation induces release of neurotransmitters,
hormones, cytokines, Ca2+, etc., in the local acupoint region, possibly being
closely associated with the production of clinical effects; 3) acupuncture
stimulation results in excitation of sensory afferent nerve fibers, triggering
neuro-regulation; 4) exosomes derived from mast cells contain multiple
neurotransmitters, hormones, cytokines, etc. to activate immune cells and sensory
afferent fibers, inducing immuno-regulation and neuro-regulation; and 5)
acupuncture stimulation induced release of Ca2+, ATP, etc. may potentiate release
and transportation of exosomes. However, current researches are lack of
excavation of network connection and transformation from basic research to
clinical application. The authors hold that the exosome, released from mast cells
by needling acupoints, acts as a messenger in network connection of nerve-mast
cell-signal molecule in the body and may be one of the key factors of therapeutic
effects.
PMID- 25845228
TI - [Diverse functions of fibulin-5 in tumors].
AB - Altered interactions between the extracellular matrix and cells play an important
part in tumorigenesis and metastasis. As a member of matricellular glycoprotein,
fibulin-5 is expressed in elastin-rich tissues and organizes the matrix
structures by interacting with many extracellular proteins. Fibulin-5 expression
is closely associated with normal embryonic development and organogenesis. Mice
deficient for the fibulin-5 gene exhibit systemic elastic fiber defects with
manifestation of loose skin, emphysematous lung and tortuous vessels.
Additionally, fibulin-5 null mice exhibited increased angiogenesis after wound
healing or PVA sponge implantation and matrigel implantation experiments show
fibulin-5 inhibited vessel formation, suggesting fibulin-5 functions as an
angiogenesis inhibitor. Fibulin-5 also plays critical roles in proliferation,
migration and invasion of certain tumors, and the effect of fibulin-5 on
tumorigenesis appears to be largely context-dependent. This effect might involve
the inhibiting action of fibulin-5 on angiogenesis. This review focuses on recent
advances in our understanding of the roles of fibulin-5 in tumorigenesis: both
tumor promoting and suppressing activity of fibulin-5 are reviewed, and the
emerging evidences of its promising potential as therapeutic options and/or
targets in the treatment of cancer also highlighted.
PMID- 25845229
TI - [Fluorescence in situ hybridization with DNA probes derived from individual
chromosomes and chromosome regions].
AB - A significant part of the eukaryotic genomes consists of repetitive DNA, which
can form large clusters or distributed along euchromatic chromosome regions.
Repeats located in chromosomal regions make a problem in analysis and
identification of the chromosomal material with fluorescence in situ
hybridization (FISH). In most cases, the identification of chromosome regions
using FISH requires detection of the signal produced with unique sequences. The
feasibility, advantages and disadvantages of traditional methods of suppression
of repetitive DNA hybridization, methods of repeats-free probe construction and
methods of chromosome-specific DNA sequences visualization using image processing
of multicolor FISH results are considered in the paper. The efficiency of
different techniques for DNA probe generation, different FISH protocols, and
image processing of obtained microscopic images depends on the genomic size and
structure of analyzing species. This problem was discussed and different
approaches were considered for the analysis of the species with very large
genome, rare species and species which specimens are too small in size to obtain
the amount of genomic and Cot-1 DNA required for suppression of repetitive DNA
hybridization.
PMID- 25845230
TI - [G-quadruplex ligands: mechanisms of anticancer action and target binding].
AB - Since the discovery of potential therapeutic value of quadruplex secondary
nucleic acids structures, many compounds that stabilize these targets were found.
Such progress became possible due to understanding of the structural features of
G-quadruplexes. Quadruplex ligands selectively suppress the growth of tumor cells
by indirect inhibition of the telomerase activity and/or attenuation of
oncogenes' overexpression. Therapeutic effect demonstrated in vivo supports the
prospect of such compounds for the development of the targeted anticancer drugs.
This review reveals the significance of G-quadruplexes as therapeutic targets and
focuses on biochemical properties of the low molecular weight quadruplex ligands.
PMID- 25845231
TI - [The gene expression of the protein SLAWD, mediating the toxic effect of
destruxin A on Spodoptera litura larvae, in procaryotic cells: purification and
characterization].
AB - Spodoptera litura is one of the most destructive phytophagous pest infesting
cotton, vegetable, oilseed and ber crops around the world. Dextruxin A (DA), is a
one of a kind microbial insecticide, which has potent toxins with bioactivity
against S. litura larvae. An abnormal wing disc (AWD) protein was identified as a
DA toxic effect protein in S. litura SL-1 cells. To better understand the role of
the AWD gene of S. litura (SLAWD) it was purified and characterized. The entire
coding region of the SLAWD gene was cloned into a pET-32a(+) expression vector
and transformed into competent Escherichia coli BL21 (DE3) cells. SDS-PAGE and
western blotting analysis and western blotting showed that the best induction
conditions were 1 mmol mL(-1) isopropyl-beta-D-thiogalactopyranoside (IPTG) for 6
h at 37 degrees C; the molecular weight of the fusion protein was 35.0 kDa. The
production of polyclonal antibodies and an enzyme-linked immunosorbent assay
(ELISA) showed that the titer of antiserum was 1:25,600; western blotting
analysis showed that the recombinant SLAWD was recognized by the anti-SLAWD
polyclonal antibody. AWD is a key protein involved in wing development in
insects. These tools will assist in the further characterization of SLAWD and
studies on the mechanism of action of destruxin A.
PMID- 25845232
TI - [Differential gene expression in incompatible interaction between Lilium regale
Wilson and Fusarium oxysporum f. sp. lilii revealed by combined SSH and
microarray analysis].
AB - Fusarium wilt, caused by a soilborne pathogen Fusarium oxysporum f. sp. lilii, is
the major disease of lily (Lilium L.). In order to isolate the genes
differentially expressed in a resistant reaction to F. oxysporum in L. regale
Wilson, a cDNA library was constructed with L. regale root during F. oxysporum
infection using the suppression subtractive hybridization (SSH), and a total of
585 unique expressed sequence tags (ESTs) were obtained. Furthermore, the gene
expression profiles in the incompatible interaction between L. regale and F.
oxysporum were revealed by oligonucleotide microarray analysis of 585 unique ESTs
comparison to the compatible interaction between a susceptible Lilium Oriental
Hybrid 'Siberia' and F. oxysporum. The result of expression profile analysis
indicated that the genes encoding pathogenesis-related proteins (PRs),
antioxidative stress enzymes, secondary metabolism enzymes, transcription
factors, signal transduction proteins as well as a large number of unknown genes
were involved in early defense response of L. regale to F. oxysporum infection.
Moreover, the following quantitative reverse transcription PCR (QRT-PCR) analysis
confirmed reliability of the oligonucleotide microarray data. In the present
study, isolation of differentially expressed genes in L. regale during response
to F. oxysporum helped to uncover the molecular mechanism associated with the
resistance of L. regale against F. oxysporum.
PMID- 25845233
TI - [Evaluation of reference genes for quantitative real-time PCR normalization in
cotton bollworm, Helicoverna armigera].
AB - Reverse-transcription quantitative real-time PCR (RT-qPCR), a sensitive technique
is being extensively employed in quantification of gene expression. However this
requires normalization with suitable reference gene (RG) which is crucial in
minimizing inter sample variations. Information regarding suitable RG is scarce
in general and more so in insects, including the cotton bollworm, Helicoverpa
armigera, an economically important pest. In management of this pest RNA
interference (RNAi), is perceived as a potential tool, which is achieved by
double-stranded RNA (dsRNA) delivery. These studies demand accurate
quantification of gene silencing. In this study we assessed the suitability of
five RGs viz. beta-actin (ACTB), 18S rRNA (18S), glyceraldehyde-3-phosphate
dehydrogenase (GAPDH), beta-tubulin (TUB) and elongation fator-1-alfa (EF1-alpha)
for gene expression studies in dsRNA treatment and across different developmental
stages of H. armigera and ranked using geNorm, NormFinder and BestKeeper software
programs. Data analysis revealed that best ranked RGs were varied in dsRNA
treatment and in developmental stages. Under dsRNA treatment, 18S and GAPDH were
more stable whereas, TUB and GAPDH were more stable across developmental stages.
We also demonstrate that inappropriate selection of RG led to erroneous
estimation of the target gene, chymotrypsin, expression. These results facilitate
accurate quantification of gene expression in H. armigera.
PMID- 25845234
TI - [Association of the nicotine and cigarette smoke toxicants metabolic (CHRNA3/5,
CYP2A6, NQO1) and DNA repair genes (XRCC1, XRCC3, XPC, XPA) with chronic
obstructive pulmonary disease].
AB - The contribution of the polymorphic markers of the CHRNA5/A3, CYP2A6, NQO1, XPC,
XRCC1, XRCC3, XPD, XPA genes to chronic obstructive pulmonary disease has been
assessed. For this purpose, analysis of the gene polymorphisms in case/control
groups in Tatar population has been performed. The CHRNA5 (rs16969968) (P =
0.0001, OR = 2.24), CHRNA3 (rs1051730) (P = 0.0001, OR = 2.72) were associated
with significantly high risk of chronic obstructive pulmonary disease in
recessive model. The disease risk was higher in homozygous carriers of normal
allele of CYP2A6 (del) (P = 0.00001, OR = 2.77). Analysis showed an association
of the NQO1 (rs1131341), XRCC1 (rs25487), XRCC3 (rs861539), XPC (rs2228001) and
XPA (rs1800975) (P = 0.000001, OR = 2.67; P = 0.00001, OR = 0.51; P = 0.0003, OR
= 1.76; P = 0.0004, OR = 0.54 and P = 0.007, OR = 0.74) in additive model with
chronic obstructive pulmonary disease. We found a significant gene-by-environment
interaction of smoking status and XPA (rs1800975) (Pinteract = 0.002);
rs16969968, rs1051730 of CHRNA3/5 genes were significantly associated with
chronic obstructive pulmonary disease only in smokers. The relationship between
the CYP2A6(CYP2A6*4) and smoking pack-years was found (P = 0.0019). The TT
genotype of XRCC3 (rs861539) were associated with decreased of lung function
parameters: vital capacity % (P = 0.0487), forced vital capacity (%) (P = 0.0032)
and forced expiratory volume in 1 s (%) (P = 0.02). The relationship between the
XPA (rs1800975) and forced expiratory volume in 1 s (%) (P = 0.0028) was found.
PMID- 25845235
TI - [Replicative association analysis of genetic markers of cognitive traits with
Alzheimer's disease in a Russian population].
AB - Replicative association analysis of Alzheimer's disease (AD) with 15 genetic
markers associated with cognitive traits in genome-wide association studies was
performed. In a Russian populations associations of rs2616984 in CSMD1 gene with
AD (OR = 1.50, 95% CI = 1.07-2.09, p-value = 0.018) and putative associations
with the disease of rs3131296 in NOTCH4 gene (OR = 1.53, 95% CI = 0.98-2.39, p
value = 0.06) and rs2229741 of NRIP1 gene (OR = 1.35, CI = 0.99-1.85, p-value =
0.061) were revealed. Combinations of epistatic interacting genes (CSMD1 and
NRIP1; NOTCH4, CSMD1 and NRIP1; TLR4, CSMD1 and NRIP1) were found, as well as
their genotypes combinations significantly associated with AD and characterized
by highest predictive values. Probable molecular mechanisms implicated in the
relation of genes under study to AD pathogenesis are discussed. Bioinformatic
analysis of biological processes, molecular functions and protein-protein
interactions of BA genes demonstrated that genes under study may play modulating
and modifying role by participation in various regulatory and signal pathways
involved in a disease development.
PMID- 25845236
TI - [Effect of tumor necrosis factor-related apoptosis-inducing ligand on developing
human oligodendrocytes in culture].
AB - Accumulating evidence suggests that proinflammatory cytokines play an important
role in white matter injury in preterm infants, a condition in which
oligodendrocyte (OL) progenitor cells are preferentially injured. We investigated
the role of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)
and its death (TRAIL-R1, TRAIL-R2) and decoy (TRAIL-R3, TRAIL-R4) receptors in
periventricular white matter injury (PWMI). We hypothesized that the maturation
dependent vulnerability of OLs to TRAIL is due to differential TRAIL receptor
expression. We previously investigated TRAIL/TRAIL receptor expression levels in
rat OLs in vivo in the context of PWMI. We found that during different
developmental stages, human OLs differentially express TRAIL receptors; there is
a progressive loss of sensitivity to TRAIL as OLs proceed through the maturation
process. Our results show that both TRAIL-R1 and -R2 are highly expressed on
human OL progenitors and pre-OLs, while TRAIL-R3 and TRAIL-R4 are mainly
expressed on immature and mature human OLs. Our results suggest that TRAIL-R1 and
TRAIL-R2 might mediate the death signal in human OL precursor cells and pre-OLs.
PMID- 25845237
TI - [Auto-inducible expression system based on the SigB-dependent ohrB promoter in
Bacillus subtilis].
AB - The reliable production of heterologous proteins is important in the field of
industrial biotechnology. This can be achieved by applying auto-inducible gene
expression systems. The development of a Bacillus subtilis expression plasmid
harboring SigB-dependent ohrB promoter was reported. The expression system was
subjected to high cell density cultivation to produce xylanase as a stable model
protein. The recombinant strain was cultured in a synthetic medium containing
glucose as the carbon source. The exponential fed-batch feeding strategy was
applied to prevent substrate inhibition. A sharp increase of xylanase activity
(about 6-fold) at the end of the fermentation was observed as a result of sigma
factor B (SigB) protein activation, supporting auto-inducibility of the
expression system. For the control strain a specific induction of the xylanase
activity was not observed. The recombinant strain was capable to offer a 5-fold
increase in xylanase activity in comparison with the control strain. In addition,
the constructed system displayed catabolite repression resistance ability. This
SigB-dependent expression system can be considered as a biotechnology tool and an
alternative to eliminate the cost of conventional inducers, e.g. isopropyl-beta
galactopyranoside.
PMID- 25845238
TI - [The role of some individual amino acid substitutions in penicillin-binding
protein (PBP2) of Neisseria gonorrhoeae in the emergence of resistance to
ceftriaxone].
AB - The goal of the study was to identify amino acid replacements in the structure of
penicillin-binding protein PBP2, which may influence on the development of
resistance N. gonorhoeae to the III cephalosporins generation. The gene penA of
50 strains of N. gonorrhoeae was sequenced: 20 strains with high sensitivity to
ceftriaxone (MIC, Minimum Inhibitory Concentration, = 0.002 mg/L) and 30 strains
with decreased sensitivity to ceftriaxone (MIC = 0.03-0.25 mg/L). The difference
of MIC sensitivity between these strains was 30-250 times. Then nucleotide
sequence was transformed into the amino acid sequence of PBP2 protein. Mutations
in the gene penA and amino acid replacements in the protein PBP2 were found in 16
of 20 strains (80%) with high sensitivity to ceftriaxone and in all strains with
decreased sensitivity to ceftriaxone. Amino acid replacements in the PBP2 protein
were compared with amino acid replacements in groups, which characterize the PBP2
structure in accordance with the international classification Ito M. The amino
acid replacement of PBP2 at positions 346, 505, 511, 517, 543, 567, 575, 576 are
associated with V group by Ito M and have features of resistance of N.
gonorrhoeae to ceftriaxone authentically (OR = 3.9 +/- 2.5; chi2 = 4.9; p <
0.05). It was shown that the replacement of glycine to serine at position 543 of
PBP2 in the analyzed strains induced the multiple increase of resistance to
ceftriaxone. These data may be significant as showing strong influence of amino
acid replacements at positions 346, 505, 511, 517, 567, 575 and, in particular,
543 for development of resistance N. gonorrhoeae strains to ceftriaxone.
PMID- 25845239
TI - [The effect of central administration of the neurotrophic factors BDNF and GDNF
on the functional activity and expression of the serotonin 5-HT2A receptors in
mice genetically predisposed to depressive-like behavior].
AB - Brain serotonin (5-HT) system plays an important role in the control of normal
and pathological behavior. 5-HT2A receptors are widely implicated in the
regulation both normal functions and psychopathologies, especially schizophrenia
and depression. Here, we investigated implication of 5-HT2A receptor in
mechanisms of neurotrophic factors BDNF and GDNF action. We found that the acute
intracerebroventricular injection of BDNF produced considerable increase in 5
HT2A receptor functional activity in ASC mice. Moreover, BDNF injection led to
the increasing of 5-HT2A receptor gene expression in the hippocampus and its
decrease in the frontal cortex without any effects in the midbrain. On the
contrary, GDNF injection failed to alter 5-HT2A receptor functional activity, but
increased the 5-HT2A receptor gene expression in the frontal cortex without any
effects in the hippocampus and midbrain. Thus, an effect of the central
administration of the neurotrophic factors BDNF and GDNF on the 5-HT2A receptor
functional activity and gene expression was shown. The results indicate the
implication of 5-HT2A receptor in the mechanisms of BDNF and GDNF action.
PMID- 25845240
TI - [Role of reactive oxygen species in the bactericidal action of quinolones-
inhibitors of DNA gyrase].
AB - Quinolone antibiotics inhibit DNA gyrase, but the induced degradation of
chromosomal DNA is determined by a complex process of joint action quinolones and
hydroxyl radical OH'. To quantify the level of stress responses and their time
dependence in bacterial cells the induced specific lux-biosensors--the bacterium
Escherichia coli, containing hybrid plasmids pColD'::lux; pSoxS'::lux;
pKatG'::lux were used in this study. It is shown that quinolones (nalidixic acid,
norfloxacin) induce SOS-response and oxidative stress with the formation of
superoxide anion O2(-) in E. coli cells. The main parameters of SOS-response and
oxidative stress, which depend on the quinolone concentration, are determined.
Formation of superoxide anion O2(-) occurs almost simultaneously with the SOS
response. The mutant strain of E. coli sodA sodB, which do not contain active
forms of superoxide dismutases SodA and SodB, is characterized by an increased
resistance to quinolones as compared to the wild type cells. At high
concentrations of quinolones (nalidixic acid-->20 MUg/mL; norfloxacin-->500
ng/mL) their bactericidal effect is partially caused by conversion of the
superoxide anion to hydrogen peroxide H2O2, conducted by superoxide dismutases
SodA and SodB, which is followed by the Fenton reaction and the formation of
toxic hydroxyl radical OH'. At low concentrations of quinolones (nalidixic acid-
<20 MUg/mL; norfloxacin--<500 ng/mL), the role of active oxygen species in the
antimicrobial effect is practically nonexistent.
PMID- 25845241
TI - [Transcripts of satellite DNA in blood plasma: probable markers of tumor growth].
AB - A recent study of human normal and tumor tissues revealed a high transcriptional
activity of pericentromeric satellite DNA repeats (they produce half of all
transcripts in tumor cells that is many times higher than in normal ones). It was
found also that the two subtypes of satellite DNA (HSATII and GSATII) are
transcribed reciprocally, i.e. there is a sharp prevalence of HSATII
transcription in tumors, while GSATII transcription prevails in the corresponding
normal tissues. As different RNAs are present in blood plasma, and some of them
serve as effectivetumor markers, we attempted for the first time to evaluate
satellite HSATII and GSATII RNAs in the blood plasma of healthy donors and cancer
patients. The RT-PCR protocol designed for this purpose allowed us to detect
transcripts of both HSATII and GSATII repeats. As it has been shown, HSATII
transcripts are more abundant than GSATII ones in plasma of healthy donors and
vice versa in plasma of cancer patients; these ratios being diametrically opposed
to those that exist within the cells. Some suggestions concerning origins of
circulating satellite RNAs and their probable role as tumor markers are
discussed.
PMID- 25845242
TI - [Spatial organization of house-keeping genes in interphase nuclei].
AB - Spatial organization of the eukaryotic genome is tightly connected to its
functioning. In particular, the interaction of gene promoters with remote
enhancer elements in active chromatin hubs, as well as the recruitment of genes
to the common transcription factories plays an important role in regulation of
gene transcription. Most of works related to the analysis of spatial interaction
of genome regulatory elements relies on models of tissue-specific genes.
Meanwhile, it remains unclear to which extent the spatial organization of
chromosomes is guided by house-keeping genes that are transcribed in most of cell
types and outnumber the transcribed tissue-specific genes. To address this
question, we used the 4C technique to characterize genome-wide the spatial
contacts of the chicken house-keeping genes CARHSP1 and TRAP1 situated on
chromosome 14. The promoters of these genes had an increased frequency of
interaction with chromosome regions enriched in CpG islands and binding motifs
for the ubiquitous transcription factor Sp1, both of which mark promoters of
house-keeping genes, and overall with transcriptionally active regions. By
contrast, the analysis of interaction of a gene poor region of chromosome 14
revealed no such preferences. The evidence for the interaction of house-keeping
gene promoters were also obtained in independent cytological experiments aimed at
visualization of non-methylated CpG islands in individual nuclei of human cells,
which showed clustering of CpG islands in the nuclear space. Altogether, the
results of our work suggest that the interaction of house-keeping genes
constitutes an important factor that determines the spatial organization of
interphase chromosomes.
PMID- 25845243
TI - [NMR screening of potential inhibitors of Citrobacter freundii methionine].
AB - Methionine gamma-lyase [EC 4.4.1.11] participates in a methionine catabolism at a
number of bacteria and protozoa eukaryotes, including pathogenic microorganisms.
Lack of this enzyme at mammals allows consider it as a perspective target for
rational antibacterial drug design. Currently in medical practice there are no
the preparations based on an inhibition of methionine gamma-lyase activity. We
present results of the search of potential inhibitors of the enzyme using the NMR
screening techniques based on identification of compounds, which able to bind
specifically to their biological target. Study included a stage of in silico
virtual screening of the library of commercially available compounds and
subsequent experimental selection of the leading compounds, capable to interact
with enzyme. Identification of binding was carried out by means of saturation
transfer difference (STD) spectroscopy and WaterLOGSY technique. At the final
stage the experimental assessment of inhibiting ability of the selected compounds
in the reaction of gamma-elimination of L-methionine catalyzed by methionine
gamma-lyase was carried out. Binding constants of two leading compounds were
determined using the WaterLOGSY method. The research expands structural group of
potential inhibitors of methionine gamma-lyase and allows approach to the design
of the inhibitors with higher efficacy.
PMID- 25845244
TI - [Molecular-and-genetic diversity of cyanophages of the family Myoviridae in Lake
Hovsgol (Mongolia)].
AB - Cyanophages of the family Myoviridae were studied in Lake Hovsgol based on the
analysis of g20 gene fragments. The analysis revealed the diversity of g20
cyanomyovirus sequences in Lake Hovsgol. It was found a great similarity of genes
from the Lake Hovsgol and Lake Baikal. Distribution of closely related virus
strains in these water bodies is attributed to close geographical location,
direct water connection and similar hydrochemical parameters of the lakes.
PMID- 25845245
TI - [Depressive symptoms and cognitive dysfunctions in patients with chronic
hepatitis B].
AB - INTRODUCTION: Pronounced symptoms of depression and disorders of cognitive
functions can be observed in patients with chronic hepatitis B. OBJECTIVE: The
objective of the study was evaluation of the severity of symptoms and predictive
factors for depression and the existence of cognitive disorders in patients with
chronic hepatitis B. METHODS: A total of 150 respondents were included in this
prospective study (50 patients with chronic hepatitis B, 50 patients with other
chronic liver diseases and 50 healthy persons). The patients with chronic
hepatitis B were homogeneous by age compared to healthy subjects (p = 0.566) and
patients with other chronic liver diseases (p = 0.528). Assessment of intensity
of depression was determined by the Hamilton Depression Rating Scale (HAMD). A
Mini Mental State Examination (MMSE) test was used to investigate the presence of
cognitive disorders. RESULTS: Significantly expressed depression was observed in
patients with chronic hepatitis B compared with healthy persons as well as the
occurrence of cognitive dysfunction (p = 0.00), while in comparison with the
patients with chronic nonviral liver diseases, depression was statistically
significantly less markedly expressed (p = 0.003). Depression and cognitive
dysfunction were more noticeable in patients with chronic hepatitis B in the
stage of liver cirrhosis in relation to the early stage of the disease.
Multivariate analysis of variables related to the sociodemographic
characteristics showed that the most significant positive predictor of depression
was more expressed in older age (over 50 years) (B = 0.276; SE = 0.092; p =
0.004). CONCLUSION: Patients with chronic hepatitis B have a higher intensity of
depression compared to healthy people, which is intensified with the progression
of the disease. The highest expression of depression is expected in the elderly.
Patients with chronic hepatitis B have a lower intensity of depression and fewer
disorders of cognitive functions than patients with other chronic liver diseases.
PMID- 25845246
TI - Changes in soft tissue profile using functional appliances in the treatment of
skeletal class II malocclusion.
AB - INTRODUCTION: The effects of orthodontic treatment are considered to be
successful if the facial harmony is achieved, while the structures of soft tissue
profile are in harmony with skeletal structures of neurocranium and
viscerocranium. In patients with skeletal distal bite caused by mandibular
retrognathism, facial esthetics is disturbed often, in terms of pronounced
convexity of the profile and change in the position and relationship of the lips.
OBJECTIVE: The aim of this study was to determine the extent of soft tissue
profile changes in patients with skeletal Class II malocclusion treated with
three different orthodontic appliances: Frankel functional regulator type I (FR
I), Balters' Bionator type I and Hotz appliance. METHODS: The study included 60
patients diagnosed with skeletal Class II malocclusion caused by mandibular
retrognathism, in the period of early mixed dentition. Each subgroup of 20
patients was treated with a variety of orthodontic appliances. On the lateral
cephalogram, before and after treatment, the following parameters were analyzed:T
angle, H angle, the height of the upper lip, the position of the upper and lower
lip in relation to the esthetic line.Within the statistical analysis the mean,
maximum, minimum, standard deviation, coefficient of variation, two-factor
analysis of variance with repeated measures and the factor analysis of variance
were calculated using ANOVA, Bonferroni test and Student's t-test. RESULTS: A
significant decrease of angles T and H was noticed in the application of FR-I,
from 21.60 degrees to 17.15 degrees , and from 16.45 degrees to 13.40 degrees
(p < 0.001). FR-I decreased the height of the upper lip from 26.15 mm to 25.85
mm, while Hotz appliance and Balters' Bionator type I increased the height of the
upper lip, thereby deteriorating esthetics of the patient. CONCLUSION: All used
orthodontic appliances lead to changes in soft tissue profile in terms of
improving facial esthetics, with the most distinctive changes in the application
of Frankel's functional regulator type I, which is the most successful appliance
for achieving the overall facial harmony of the patient.
PMID- 25845247
TI - Application of digital radiography for measuring in clinical dental practice.
AB - INTRODUCTION: The recent literature data points out a rising application of
digital radiography--radiovisiography (RVG)--in dental clinical practice.
OBJECTIVE: The aim of this study was to apply and compare RVG with the
conventional radiographic technique (CRDG) in terms of accuracy in linear
measurement in dentistry. METHODS: Measurements were done on the mandibular dogs
teeth considering incisors crown width and height of the surrounding alveolar
bone using RVG and CRDG.The control technique (CONT) involved values obtained by
direct gauging in dogs mouth. Each measuring was done by two examiners. RESULTS:
Considering the incisors' crown width, there were no significant statistical
difference in measurement using CRDG, RVG and CONT technique (p > 0.01).
Concerning the alveolar height gauging there were no significant difference in
recorded values between the two radiographic techniques (p > 0.01). The high
level of inter-examiner agreement was observed for scoring in all techniques
(CRDG, RVG and CONT). CONCLUSION: Although RVG did not expose more accuracy
comparing to CRDG, having opulent tool service the first technique contributed
more comfortable work during measuring procedures in this study.
PMID- 25845248
TI - [The role of cardiac pacing therapy in the management of carotid sinus syndrome].
AB - INTRODUCTION: Carotid sinus syndrome is characterized by a hypersensitive carotid
sinus and syncope. Although we have clear guidelines for the diagnosis and
treatment of carotid sinus syndrome, the efficacy of pacing therapy with this
indication has not been the subject of many studies. OBJECTIVE: This study aimed
to assess the efficacy and safety of pacing therapy in the treatment of patients
with carotid sinus syndrome and to determine the factors contributing to symp-
toms recurrence after pacemaker implantation. METHODS: This study was
retrospective and included 32 patients in whom a pacemaker was implanted due to
carotid sinus syn- drome at the Pacemaker Center, Clinical Center of Serbia, be-
tween April 2005 and April 2012. Carotid sinus massage and head-up tilt test
(HUTT) were performed to select patients with cardioinhibitory and mixed type
carotid sinus syndrome, who were enrolled to the study. RESULTS: The mean age of
patients was 65.6 +/- 11.5 years and 20 (62.5%) were men. The mean follow-up
period was 4.3 +/- 1.9 years. HUTT was performed in 3 (9.4%) patients. Twenty
seven (84.4%) patients presented with cardioinhibitory and 5 (15.6%) with mixed
type of carotid sinus syndrome. After pacemaker implantation, 22 (68.7%) patients
had no further symptoms, 8 (25.0%) had syncope and 2 (6.3%) presyncope.The mixed
type of the disease (HR 3.1; 95% CI 1.4-5.1; p = 0.021) and implanta- tion of
pacemaker in WI mode (HR 1.8; 95% CI 1.1-3.2; p = 0.034) were independent
predictors of symptoms recurrence. There were 3 (9.4%) perioperative surgical
complications. CONCLUSION: Pacemaker therapy is an effective and safe treat- ment
for patients with carotid sinus syndrome. As predictors of symptoms persistence
after pacemaker implantation in our population, we identified the implantation of
pacemaker in WI mode and the mixed type of carotid sinus syndrome.
PMID- 25845249
TI - Osteoporosis--a risk factor for cardiovascular diseases: a follow-up study.
AB - INTRODUCTION: Cardiovascular (CV) diseases and bone fractures due to osteoporosis
are the leading causes of death in the elderly. OBJECTIVE: The aim of this study
was to demonstrate a correlation between the overall risk for CV events, and low
bone density in postmenopausal women, and its impact on the incidence of serious
CV events. METHODS: Our prospective study involved 300 postmenopausal women. All
the examinees were divided into three groups based on their measured bone
density: Group I--84 examinees with osteoporosis; Group II--115 examinees with
osteopenia; and Group III--101 examinees with normal bone density. In all
examinees the overall ten-year risk for a fatal CV event was calculated using the
SCORE system tables. RESULTS: After a 36-month follow-up, CV events occurred in
19 (6.3%) examinees. Significant differences in the incidence of CV events were
demonstrated between the patients with osteoporosis, osteopenia, and normal bone
density (chi2 = 28.7; p < 0.001), as well as between those with a high and low CV
risk (chi2 = 22.6; p < 0.001). Multivariate logistic regression analysis showed
that smoking (OR: 2.23; 95% CI: 1.02 to 6.19; p = 0.035), and increase of overall
CV score (OR: 1.36; 95% CI: 1.17 to 1.58; p < 0.001) are associated with
increased CV event risk, while the increase of T score value is associated with
decreased risk of CV event (OR: 0.42; 95% CI: 0.25 to 0.73; p = 0.002).
CONCLUSION: Measurement of bone density with a standard assessment of the total
CV risk could be useful for selecting women who need intensive prevention and
treatment of atherosclerosis.
PMID- 25845250
TI - Boceprevir in genotype 1 chronic hepatitis C: first experiences in Serbia.
AB - INTRODUCTION: The triple therapy which consists of one of the protease inhibitor
plus pegylated interferon and ribavirin (P/R) is the standard of care for the
treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection both in
treatment-naive and experienced patients. OBJECTIVE: The aim of this study was to
analyze the efficacy and tolerability of this regime in hospital practice in
Serbia. METHODS: From July 2012 to October 2012, 20 previously treated patients
with advanced fibrosis and HCV G1 infection were included in the triple antiviral
regimen in six referral centers in Serbia. All patients were treated with
response guide therapy (RGT) regime according to the boceprevir treatment
protocol. During the 4-week lead-in period all patients received peginterferon
plus ribavirin. After the lead-in pe- riod boceprevir was added in the dosage of
800 mg three times a day orally.The subsequent treatment varied according to
virologic response and fibrosis. During the therapy HCV RNA level was measured at
week 4, 8, 12, 24 of the treatment for the assessment of virologic response
profile. All patients who completed therapy were assessed at the end of the
treatment and at the end of an additional 24-week treatment-free period for a
sustained virologic response (SVR). RESULTS: The total of 20 patients with
advanced fibrosis was treated. Among patients with an undetectable HCV RNA level
at week 8 the rate of SVR was 100%. No patient with decrease in the HCV RNA level
< 1 log 10 IU/ml at treatment week 4 achieved SVR. The overall rate of SVR was
55%. The safety profile of the treatment regimen was good. Anemia was reported in
25% of patients. There was no life-threatening treatment adverse event.
CONCLUSION: Boceprevir in combination with P/R achieved fairly good SVR rates in
patients that were"most difficult to treat"who failed on dual therapy and was
effective among patients with cirrhosis.
PMID- 25845251
TI - Significance of immunohistochemical expression of p16INK4a in the differentiation
of inflammatory and preneoplastic cervical lesions.
AB - INTRODUCTION: Most studies point at the main role of humanpapilloma virus (HPV)
in the development of dysplasia and cervical cancer. Due to the low specificity
and sensitivity of morphological diagnostic methods it is necessary to find an
adequate marker which would be introduced in the screening program for cervical
cancer. Most research suggests that p16INK4a is a specific and sensitive marker.
OBJECTIVE: The aim of this research was to determine the presence of p16INK4a
expression in inflammatory and preneoplastic lesions of the cervix. METHODS: The
study was performed on 73 samples of cervical biopsy. In 34 patients a
preneoplastic change (dysplasia) in the stratified squamous cervix epithelium was
found, and in 39 a non-specific inflammatory process was disclosed. In all
samples, immunohistochemical analysis using antibodies to p16INK4a was performed.
RESULTS: The expression of p16INK4a was verified in 67.65% of cases in dysplastic
cervical lesions and 38.5% of the inflammatory lesions. A statistically
significant difference was determined in the presence and grade of expression
between dysplastic and inflammatory lesions of the cervix (chi2 = 24.16; p <
0.001). The expression was more frequent and had a higher grade in dysplastic
lesions with high grade and showed a statistically significant difference
compared to the expression in low-grade dysplasia (chi2 = 21.48; p < 0.001).
CONCLUSION: The analysis of the presence of p16INK4a can differentiate non
neoplastic from preneoplastic changes in the cervix. It is recommended to use
immunocytochemical and immunohistochemical analysis using p16INK4a in
interpreting borderline lesions of the cervix.
PMID- 25845252
TI - Estimation of angiotensin-converting enzyme inhibitors protein binding degree
using chromatographic hydrophobicity data.
AB - INTRODUCTION: Angiotensin-converting enzyme (ACE) inhibitors represent a
significant group of drugs primarily used in the treatment of hypertension and
congestive heart failure. OBJECTIVE: Selected ACE inhibitors (enalapril,
quinapril, fosinopril, lisinopril, cilazapril) were studied in order to establish
a fast and easy estimation method of their plasma protein binding degree based on
their lipophilicity data. METHODS: Chromatographic hydrophobicity data (parameter
C0) were obtained on cellulose layers under conditions of normal-phase thin-layer
chromatography (NPTLC), using different binary solvent systems. The ACE
inhibitors lipophilicity descriptors (logP) values were calculated using the
software package Virtual Computational Chemistry Laboratory.The ACE inhibitors
plasma protein binding data were collected from relevant literature. RESULTS: ACE
inhibitors protein binding data varied from negligible (lisinopril) to 99%
(fosinopril). The calculated lipophilicity descriptors, logP(KOWWIN) values
ranged from -0.94 (lisinopril) to 6.61 (fosinopril). Good correlations were
established between plasma protein binding values and calculated logP(KOWWIN)
values (R2 = 0.8026) as well as chromatographic hydrophobicity data, C0
parameters (R2 = 0.7662). Even though good correlation coefficients (R2) were
obtained in both relations, unacceptable probability value with p > 0.05 was
found in relation between protein binding data and calculated logP(KOWWIN)
values. Subsequently, taking into consideration the request for probability value
lower than 0.05, a better relationship was observed between protein binding data
and chromatographically obtained hydrophobicity parameters C0 values. CONCLUSION:
Cellulose layers are easily available and cost effective sorbent to assess
hydrophobicity. Experimentally obtained data on ACE inhibitors hydrophobicity and
plasma protein binding estimation are important parameters in evaluating
bioavailability of these drugs.
PMID- 25845253
TI - [Applying the model of excellence in dental healthcare].
AB - INTRODUCTION: Models of excellence are considered a practical tool in the field
of management that should help a variety of organizations, including dental, to
carry out the measurement of the quality of provided services, and so define
their position in relation to excellence. The quality of healthcare implies the
degree within which the system of healthcare and health services increases the
likelihood of positive treatment outcome. OBJECTIVE: The aim of the present study
was to define a model of excellence in the field of dental healthcare (DHC) in
the Republic of Serbia and suggest the model of DHC whose services will have the
characteristics of outstanding service in the dental practice. METHODS: In this
study a specially designed questionnaire was used for the assessment of the
maturity level of applied management regarding quality in healthcare
organizations of the Republic of Serbia. The questionnaire consists of 13 units
and a total of 240 questions. RESULTS The results of the study were discussed
involving four areas: (1) defining the main criteria and sub-criteria, (2) the
elements of excellence of DHC in the Republic of Serbia, (3) the quality of DHC
in the Republic of Serbia, and (4) defining the framework of the model of
excellence for the DHC in the Republic of Serbia. The main criteria which defined
the framework and implementation model of excellence in the field of DHC in
Serbia were: leadership, management, human resources, policy and strategy, other
resources, processes, patients' satisfaction, employee's satisfaction, impact on
society and business results. The model had two main parts: the possibilities for
the first five criteria and options for the other four criteria. CONCLUSION:
Excellence in DHC business as well as the excellence of provided dental services
are increasingly becoming the norm and good practice, and progressively less the
exception.
PMID- 25845254
TI - Primary lymphoma of the brain in a young man whose brother died of hemophagocytic
lymphohistiocytosis: case report.
AB - INTRODUCTION: We represent the unique occurrence of primary central nervous
system lymphoma (PCNSL) in a patient whose brother died of genetically confirmed
hemophagocytic lymphohistiocytosis (HLH). CASE OUTLINE: We report a case of a 25
year-old male patient with primary aggressive diffuse large B-cell lymphoma
affecting the brain and PCNSL. Despite one year of medical treatment outcome was
lethal. However, our patient had a relatively longer survival compared to median
survival time for PCNSL. Additionally, he had two older brothers who died at the
age of about 11 years. One died of fulminate malignancy, shortly after pediatric
admission, before the diagnosis could be established. The other one died from
genetically confirmed (perforin mutation/PRF1) HLH. Our patient was heterozygous
carrier of perforin mutation representing the genetic marker for HLH. Our
patient's father was the carrier of the same mutation but had no symptoms of any
disease. CONCLUSION: This case points at the presence of HLH and diffuse large B
cell PCNSL in brothers. Extensive assessment of patients with probable PCNSL and
familial HLH is necessary, including genetic analysis for HLH.
PMID- 25845255
TI - Intracardiac extension of the inferior vena cava leiomyosarcoma with Budd-Chiari
syndrome presentation: a case report.
AB - INTRODUCTION: Leiomyosarcomas of the inferior vena cava are rare malignant
tumors. A limited number of these cases have been described so far. Only few of
them have intracardiac propagation and surgery is rarely undertaken for their
treatment. CASE OUTLINE: We present a 52-year-old female patient in whom
leiomyosarcoma of the inferior vena cava with intracardiac propagation was
diagnosed. The patient underwent successful surgical treatment with complete
removal of the tumor and direct suture of the inferior vena cava. No additional
modalities of therapy were undertaken. CONCLUSION: Surgery, without radiation
therapy can be a successful option for the treatment of inferior vena cava
leiomyosarcoma with a good short-term result.
PMID- 25845256
TI - Surgical treatment of median arcuate ligament syndrome: case report and review of
literature.
AB - INTRODUCTION: Median arcuate ligament (MAL) syndrome, also called celiac trunk
compression syndrome (CACS) or Dunbar syndrome is a rare disorder caused by
compression of the celiac artery by median arcuate ligament of the diaphragm,
which leads to mesenteric ischemia and chronic abdominal angina. The typical
clinical triad of symptoms includes postprandial epigastric pain, weight loss and
vomiting. The gold standard for MAL syndrome diagnosis is selective angiography,
while in symptomatic patients with angiographically verified stenosis the optimal
therapy is surgical treatment. CASE OUTLINE: A 40-year-old male patient was
presented with epigastric pain, followed by dyspepsia and weight loss. The upper
endoscopy showed gastric and duodenal distention with prominent folds of gastric
mucosa and slow peristalsis. Selective angiography showed stenosis (90%) of
initial segment of the celiac trunk. Adhesiolysis with the transection of the
median arcuate ligament was performed. Due to repeated symptoms, the patient was
reoperated on the 10th postoperative day with performed adhesiolysis and
gastrostomy for gastric nutrition. Two months later, the patient was
rehospitalized for closure of gastrostomy. At five years follow-up, selective
angiography showed no stenosis of the initial segment of the celiac artery.
CONCLUSION: Despite the existing controversy concerning pathophysiological
mechanism, the clinical presentation and treatment modalities of patients with
MAL syndrome, it is evident that careful selection and adequate surgical
treatment may significantly reduce symptoms in these patients.
PMID- 25845257
TI - [Axial torsion and gangrene of Meckel's diverticulum: case report].
AB - INTRODUCTION: Meckel's diverticulum (MD) is the most prevalent congenital anomaly
of small intestine. It develops due to the incomplete obliteration of
omphalomesenterict duct which normally undergoes obliteration during the seventh
week of gestation. In the majority of cases MD is asymptomatic but it may cause
various complications, such as bleeding, intestinal obstruction and inflammation.
Cases of umbilical sinuses, fistulas and neoplasms related with MD have been
reported, but extremely rare gangrene due to its axial torsion, especially in
children, as is the case of our patients. CASE OUTLINE: An 11-year-old boy
admitted to hospital due to 24 hours epigastric pain, vomiting and malaise. After
a complete physical examination, and appropriate pre-surgical laboratory and
radiographic tests, surgical exploration was performed with a midline abdominal
incision. On 60th cm proximal to the ileocecal valve we found a long and in a
narrow based ganrenous MD with axial torsion and fibrotic cord extending from the
tip of MD to the ileal mesentery. Surrounding ileum had normal appearance. A
demarcation and subsequent resection of MD and the surrounding ileum was
performed with end-to-end ileal anastomosis. Postoperative recovery was
successful and the patient was discharged after six days. CONCLUSION: Axial
torsion of MD is presented with non-specific abdominal symptoms and difficult
preoperative diagnosis. The choice of diagnosis and therapy is surgical
exploration and resection of MD.
PMID- 25845258
TI - Granulomatosis with polyangitis (Wegener's) and central nervous system
involvement: case report.
AB - INTRODUCTION: Granulomatosis with polyangitis (Wegener's) is an antineutrophil
cytoplasmic antibody (PR3-ANCA)-associated vasculitis, which commonly involves
the upper and lower respiratory tracts and kidneys. Central nervous system
involvement is reported in less than 11%, and rarely present at onset. CASE
OUTLINE: We report the case of a 41-year-old male patient with a high disease
activity, large organ involvement, as well as central nervous system
manifestations presented at onset.Treatment with intravenous pulse
methylprednisolone, followed by the pulsed doses of cyclophosphamide was induced.
After 6 months of cyclophosphamide pulse therapy a remission was achieved. Next,
azathioprine was used for maintenance during the next 18 months.There were no
disease flares during 24-month follow-up. CONCLUSION: Granulomatosis with
polyangitis (Wegener's) with large organ involvement, affecting the central
nervous system structures require a rapid diagnosis and intensive medication
treatment in order to prevent or reduce irreversible damage. Our experience
confirms the findings reported in the literature that the severe forms of the
disease are associated with increased probability of achieving remission, which
reflects increased responsiveness of such patients to immunosuppressant therapy.
PMID- 25845259
TI - Raw milk consumption and health.
AB - Contrary to the safe practices of milk pasteurization or sterilization, which
effectively reduce foodborne outbreaks incidence associated with raw milk and
dairy products use, outbreaks caused by such products continue to occur. Despite
this fact, a worldwide movement advocating for the rights of raw milk and cheese
selling and consumption, due to their specific nutritive characteristics, has
strengthened significantly in recent years. Traditional agricultural
manufacturers from Serbia still sell products related to thermally unprocessed
milk, such as cottage cheese and raw cream. In AP Vojvodina during the period of
1981-2010 a total of 179 foodborne outbreaks were reported, where the
incriminated cause of the outbreak were milk or diary. In 126 (70.39%) outbreaks,
totaling 2276 sick individuals and one casualty, it was confirmed that the
incriminated food was from the group of dairy products. In 48 instances (26.82%),
bacteriological tests confirmed that milk and dairy products were excluded as the
outbreak causes, while in another 5 (2.79%) outbreaks, microbiological analysis
of food failed to confirm any relation to the actual epidemiological instances.
In some cases, bacteriological testing of incriminated foods was not possible. In
the cases of outbreaks associated with the consumption of milk and dairy
products, traditional raw milk products were cited as being used. Consumption of
unpasteurized milk and cheese represents public health threat. National and
international rules ensuring use of safe products for human consumption have to
set rules of trade of thermally processed milk and products on the market.
PMID- 25845260
TI - [Injuries and vital reactions patterns in hanging].
AB - Hanging is a form of ligature strangulation in which the force applied to the
neck is derived from the gravitational drag of one's own body weight. A furrow
dessication is the most common form of ligature mark on the skin. The furrow is a
postmortem phenomenon due to ligature pressure and it is more detectable as the
suspension time becomes longer.Vital reaction is a phenomenon that shows if the
injury was pre- mortal. Vital signs could be present at the injury site, thus it
is termed as local, but they could also be remote from the injury site, and then
they are termed general vital signs. The presence and recognition of any vital
reaction in each pathoforensic case indicate vitality of certain injury, which is
sometimes exceptionally useful in solving the case under investigation. Although
in cases of hanging there is usually no question about the vitality of injury,
this does not mean that one should not recognize the type of vital reactions and
location of occurrence of these phenomena in such cases. Most often they can be
also useful in the reconstruction of the mechanism. This paper presents most
common vital reactions in hanging, with explanation of their underlying
mechanisms, and their significance in forensic pathology is pointed out.
PMID- 25845261
TI - Fifty years of discovery of alpha-fetoprotein as the first tumor marker.
AB - Alpha-fetoprotein represents the most prominent oncobiomarker, widely used in the
diagnosis of hepatocellular carcinoma for monitoring of tumor progression,
presence of metastasis, assessment of cancer prognosis and successful antitumor
therapeutic measures. Yuri Semenovich Tatarinov is a Russian scientist who first
published antigen specific for human hepatocellular carcinoma in 1963. To
commemorate the 50th anniversary of the discovery of alpha-fetoprotein, 9th
International Scientific-Practical Conference entitled "Achievements of
fundamental science and translational medicine capabilities in solving actual
problems of practical public health" was held from May 6-8th, 2013 in Astrakhan,
Russia.The conference was held in memory of historical scientific work of Yuri
Semenovich Tatarinov.
PMID- 25845262
TI - Giovanni Battista Monteggia (1762-1815).
AB - Giovanni Battista Monteggia was born in Laverne on the 8th of August 1762.
Monteggia started his education in the School of Surgery at the Hospital Maggiore
in Milano in 1779.This hospital was called "Big House"and it is one of the oldest
medical institutions in Italy. He passed exam in surgery in 1781. Monteggia was
promoted to assistant at surgery in Maggiore hospital in 1790. He was among the
first who gave a complete clinical description of polio. He described traumatic
hip dislocation and special forearm fracture which was named after him. Strictly
speaking, a Monteggia fracture is a fracture of the proximal third of the ulna
with an anterior dislocation of the radial head. Monteggia became a member of the
renewed Institute of Science, Literature and Art in Milano in 1813.
PMID- 25845263
TI - [Contemporary nuclear medicine diagnostics of neuroendocrine tumors].
AB - The new positron emission tomography (PET/CT) methods for neuroendocrine tumors
detection are presented and compared with classic, conventional methods.
Conventional methods use a gamma scintillation camera for patients with
neuroendocrine tumor imaging, after intravenous injection of one of the following
radiopharmaceuticals: 1) somatostatin analogues labeled with indium-111 (111In
pentetreotide) or technetium-99m (99mTc-EDDA/HYNIC-TOC); 2) noradrenaline
analogue labeled with iodine-131 or -123 (131/123I-MIBG); or 3) 99mTc(V)-DMSA.
Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor
imaging, after intravenous injection of pharmaceuticals labeled with positron
emitters [fluorine-18 (18F), galium-68 (68Ga), or carbon-11 (11C)]: 1) glucose
analogue (18FDG); 2) somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga
DOTANOC); 3) aminoacid precursors of bioamines: [a) dopamine precursor 18F-DOPA
(6-18F-dihydroxyphenylalanine), b) serotonin precursor 11C-5HTP (11C-5
hydroxytryptophan)]; or 4) dopamine analogue 18F-DA (6-18F-fluorodopamine).
Conventional and contemporary (PET/ CT) somatostatin receptor detection showed
identical high spe- cificity (92%), but conventional had very low sensitivity
(52%) compared to PET/CT (97%). It means that almost every second neuroendocrine
tumor detected by contemporary method cannot be discovered using conventional
(classic) method. In metastatic pheochromocytoma detection contemporary (PET/ CT)
methods (18F-DOPA and 18F-DA) have higher sensitivity than conventional
(131I/123I-MIBG). In medullary thyroid carcinoma diagnostics contemporary method
([18F-DOPA) is more sensitive than conventional 99mTc(V)-DMSA method, and is
similar to 18FDG, computed tomography and magnetic resonance. In carcinoid
detection contemporary method (18F-DOPA) shows similar results with contemporary
somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine
tumors it is worse. To conclude, contemporary (PET/CT) methods for somatostatin
receptor detection (68Ga-DOTATOC/-NOC/-TATE) in neuroendocrine tumors are much
more sensitive (almost twice) and more accurate than conventional. Therefore the
classical methods should be urgently replaced by contemporary methods.
PMID- 25845264
TI - Writing a case report in English.
AB - A well-written case report is a clear, concise and informative paper, aimed at
professionals from different fields of medicine, with the clear purpose to
explain what lesson is to be learnt from the experience. The aim of this paper is
to suggest useful guidelines for writing a good case report. It briefly reflects
different "moves"in this piece of academic writing, thus outlining the required
form, as well as the four principles of good writing: clarity, honesty, reality
and relevance.
PMID- 25845265
TI - Physical-Chemical Characterization of Fruit Purees and Relationship with Sensory
Analysis Carried out by Infants (12 to 24 mo).
AB - Fruit purees are one of the foods earliest introduced foods in infants' diet
during the complementary period. The rheological characteristics together with
the sensory analysis are decisive factors for the acceptance of the food product
by the infant. The sensory analysis of three commercial fruit purees (mixed
fruits, pear, and plum) was studied by employing a new objective sensory
parameter named as SAIR (Sensory Acceptance by Infants Ratio), which is the
quotient between the percentage of puree consumed (%) by the time (seconds)
throughout the storage time. In parallel, the rheological characteristics of the
purees were analyzed in order to obtain a relationship with the SAIR parameter.
It was proved that the best acceptance of the product (higher SAIR) was observed
for such purees showing a lower apparent viscosity (lower consistency index, "K")
and a less pseudoplastic behavior (higher flow behavior index, "n"). These
results may help to obtain higher acceptance values based on easy obtainable and
objective parameters.
PMID- 25845266
TI - Stimulus-dependent augmented gamma oscillatory activity between the functionally
connected cortical neurons in the primary visual cortex.
AB - Neuronal assemblies typically synchronise within the gamma oscillatory band (30
80 Hz) and are fundamental to information processing. Despite numerous
investigations, the exact mechanisms and origins of gamma oscillations are yet to
be known. Here, through multiunit recordings in the primary visual cortex of
cats, we show that the strength of gamma power (20-40 and 60-80 Hz) is
significantly stronger between the functionally connected units than between the
unconnected units within an assembly. Furthermore, there is increased frequency
coherence in the gamma band between the connected units than between the
unconnected units. Finally, the higher gamma rhythms (60-80 Hz) are mostly linked
to the fast-spiking neurons. These results led us to postulate that gamma
oscillations are intrinsically generated between the connected units within cell
assemblies (microcircuits) in relation to the stimulus within an emergent '50-ms
temporal window of opportunity'.
PMID- 25845267
TI - Shifts in Buchnera aphidicola density in soybean aphids (Aphis glycines) feeding
on virus-infected soybean.
AB - Vertically transmitted bacterial symbionts are common in arthropods. Aphids
undergo an obligate symbiosis with Buchnera aphidicola, which provides essential
amino acids to its host and contributes directly to nymph growth and
reproduction. We previously found that newly adult Aphis glycines feeding on
soybean infected with the beetle-transmitted Bean pod mottle virus (BPMV) had
significantly reduced fecundity. We hypothesized that the reduced fecundity was
attributable to detrimental impacts of the virus on the aphid microbiome, namely
Buchnera. To test this, mRNA sequencing and quantitative real-time PCR were used
to assay Buchnera transcript abundance and titre in A. glycines feeding on
Soybean mosaic virus-infected, BPMV-infected, and healthy soybean for up to 14
days. Our results indicated that Buchnera density was lower and ultimately
suppressed in aphids feeding on virus-infected soybean. While the decreased
Buchnera titre may be associated with reduced aphid fecundity, additional
mechanisms are probably involved. The present report begins to describe how
interactions among insects, plants, and plant pathogens influence endosymbiont
population dynamics.
PMID- 25845268
TI - Negative pressure wound therapy technologies for chronic wound care in the home
setting: A systematic review.
AB - The use of negative pressure wound therapy (NPWT) is increasing in both the
inpatient and outpatient settings. We conducted a systematic review on the
efficacy and safety of NPWT for the treatment of chronic wounds in the home
setting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled
Trials, and the Cumulative Index to Nursing and Allied Health Literature, up to
June 2014. Two independent reviewers screened search results. Seven studies met
our criteria for inclusion. Six of the studies compared NPWT devices to other
wound care methods and one study compared two different NPWT technologies. Data
were limited by variability in the types of comparator groups, methodological
limitations, and poor reporting of outcomes. We were unable to draw conclusions
about the efficacy or safety of NPWT for the treatment of chronic wounds in the
home setting due to the insufficient evidence. Consensus is needed on the methods
of conducting and reporting wound care research so that future studies are able
inform decisions about the use of NPWT in the home environment for chronic
wounds.
PMID- 25845269
TI - Sex differences in the pathways to symptoms of alcohol use disorder: a study of
opposite-sex twin pairs.
AB - BACKGROUND: We sought to develop an empirical, broad-based developmental model
for sex differences in risk for symptoms of alcohol use disorders, here called
alcohol problems (APs). METHODS: We assessed 18 risk factors in 5 developmental
tiers in both members of 1,377 opposite-sex dizygotic twin pairs from the
Virginia population-based twin registry. Analyses were conducted by structural
modeling, examining within-pair differences. RESULTS: The best-fitting model
explained 73% of the variance in men and 71% in women for last year AP. Forty
nine percent of paths differed significantly across sexes. Ten variables had
appreciably different predictive effects on AP in males versus females. Three
were stronger in females: familial risk, early-onset anxiety disorders, and
nicotine dependence. Seven predictors had a stronger total effect in males:
novelty seeking, conduct disorder, childhood sexual abuse, parental loss,
neuroticism, low self-esteem, and low marital satisfaction. CONCLUSIONS: In a co
twin control design, which matches sisters and brothers on genetic and familial
environmental background, we found numerous sex differences in predictors of last
year AP. Factors that were more prominent in men and in women were diverse,
reflecting both internalizing and externalizing psychopathology. The model was
slightly more successful at predicting AP in men than in women.
PMID- 25845270
TI - Mode of delivery and childhood fractional exhaled nitric oxide, interrupter
resistance and asthma: the Generation R study.
AB - BACKGROUND: Previous studies suggest that caesarean section may influence the
risk of childhood asthma. We examined the associations of different modes of
delivery with childhood wheezing patterns, asthma, fractional exhaled nitric
oxide (FeNO) and airway interrupter resistance (Rint) up to school age. METHODS:
This study among 6,128 children was embedded in a population-based prospective
cohort study. Information on mode of delivery was obtained from midwives and
hospital registries. Wheezing patterns from birth onwards and ever physician
diagnosed asthma at age 6 yr were assessed by questionnaires. FeNO and Rint were
measured at age 6 yr. We used multivariate polynomial, logistic and linear
regression models. RESULTS: Compared with vaginal delivery, caesarean section was
associated with increased risks of early and persistent wheezing up to school age
[odds ratios (95% confidence interval): 1.36 (1.06, 1.75) and 1.73 (1.24, 2.40),
respectively]. The effect sizes of elective and emergency caesarean section with
wheezing outcomes were similar. Only elective caesarean section was associated
with a higher FeNO level [sympercent (95% CI): 12.7 (0.6, 24.8)]. We did not
observe associations of mode of delivery with asthma or Rint. Also, vacuum- or
forceps-assisted vaginal delivery was not associated with any asthma or related
outcome. CONCLUSIONS: Both elective and emergency caesarean sections are
associated with increased risks of early and persistent wheezing up to school
age. This might be explained by increased airway inflammation reflected by higher
FeNO levels.
PMID- 25845271
TI - Reference values of serum IgG and IgM levels in preterm and term newborns.
AB - AIM: Although, variations of normal immunoglobulin (Ig) levels in different
gestational age and birth weight groups have been studied so far, data are still
limited in newborns, especially in preterm infants. The aim of this study was to
determine serum IgG and IgM levels in newborns in order to generate a reference
standard for neonatal intensive care unit (NICU) and address the variations in
preterm babies. METHODS: This study was conducted from June 2012 to June 2013 in
a level III NICU. A total of 300 newborn infants hospitalized within first 72 h
were included in the study. The quantification of serum IgG and IgM was performed
by nephelometric method. RESULTS: Both serum IgG and IgM levels were increased in
correlation with increased gestational age and birth weight. CONCLUSION: The
reference values of serum IgG and IgM levels should be further evaluated in
larger series with the presented data in this article. In addition, preterm
babies appear to have lower Ig levels thus carry the risk of relevant morbidity.
PMID- 25845272
TI - Sirenomelia: a review of embryogenic theories and discussion of the differences
from caudal regression syndrome.
AB - OBJECTIVE: To discuss the pathological features of sirenomelia in the light of
our 10 cases and review the current theories. METHODS: We identified 10 patients
with sirenomelia from our hospital database. All clinical details and the autopsy
features of 10 cases were noted. RESULTS: Of the 10 children with sirenomelia
seven had bilateral renal agenesis, three had bladder agenesis and one had a
renal hypoplasia. Single umbilical artery was found in 60% of children with
sirenomelia. External genitalia was ambiguous in seven of 10 patients.
CONCLUSIONS: Even though the etiology of caudal regression syndrome (CRS) and
sirenomelia remains unknown we tend to believe that sirenomelia and CRS might be
different entities.
PMID- 25845273
TI - The role of interleukin-17 in intrahepatic cholestasis of pregnancy.
AB - OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is the most common
pregnancy-specific liver disease, is characterized by pruritus, abnormal liver
function and elevated serum bile acid levels. The main cause of ICP has not yet
been identified. We aimed to provide a new perspective to the pathogenesis of by
investigating the possible association of circulating interleukin-17 (IL-17) that
is a recently discovered proinflammatory cytokine levels with ICP. MATERIALS AND
METHODS: In this controlled cross-sectional study, maternal venous blood samples
were obtained from 33 consecutive pregnant women with ICP (15 with mild and 18
with severe forms of the disease) and 25 healthy women with uncomplicated
pregnancies (as the control group) and IL-17 levels were compared among the
groups. RESULTS: Although serum IL-17 levels were significantly higher in the
severe ICP group than in the control group (p = 0.022), there were no significant
differences between the mild and severe ICP groups or between the control and
mild ICP groups. CONCLUSION: Explaining the mechanisms of hepatocyte injury might
contribute to the existing therapeutic strategies for treating cholestatic
diseases. Changes in IL-17 levels may shed light on the pathogenesis of ICP.
PMID- 25845274
TI - Use of intracervical balloons and chorioamnionitis in term premature rupture of
membranes.
AB - OBJECTIVE: To determine whether ripening and induction in patients with term
premature rupture of membranes (PROM) via intracervical balloon placement (ICB)
increases the risk of chorioamnionitis when compared to women with term PROM
ripened and induced with other methods. STUDY DESIGN: A retrospective cohort
study of term singleton gestations undergoing ripening and induction after PROM
between July 2009 and June 2012 was conducted. Exposure of interest was ICB
placement. Primary outcome of interest was chorioamnionitis. Statistical analysis
included bivariate and multivariate techniques. RESULTS: Of 124 term PROM
patients, 42 were ripened by ICB with or without oxytocin (33.9%) and 82 were
ripened and induced with oxytocin (66.1%). More women ripened with an ICB were
nulliparous (n = 35, 83.3% ICB versus n = 44, 53.7% oxytocin, p = 0.001).
Chorioamnionitis was slightly more common in women ripened with ICB and/or
oxytocin versus oxytocin alone but difference did not reach statistical
significance (p = 0.10). The rate of cesarean delivery, intrauterine pressure
catheter (IUPC) use, and median lengths of membrane rupture and active labor were
higher in the ICB group. After adjustment, chorioamnionitis was not correlated
with ICB placement but with nulliparity [AOR 12.5 (1.36, 114.6), p = 0.03] and
IUPC use [AOR 4.39 (1.04, 18.5), p = 0.04]. CONCLUSION: Nulliparity and IUPC, not
ICB placement, were associated with chorioamnionitis.
PMID- 25845275
TI - The role of placental alpha microglobulin-1 amnisure in determining the status of
the fetal membranes; its association with preterm birth. Traditions ...
traditions ....
AB - The integrity of the fetal amnion-chorion is an imperative for the preservation
of a normal pregnancy in the human. The diagnosis of the status of the fetal
membranes has traditionally been reduced to either intact or ruptured. In the
last decades, evidence has accumulated demonstrating that this clinical approach
may well be an over simplification. Practically, all maternal organs experienced
physiologic or eventually pathologic changes during the length of the gestational
period. We propose that the fetal membranes are also significantly impacted by
those changes. The accurate, specific, simplified and low-cost diagnosis of the
status of the fetal membranes is of critical importance for the assessment of
risk to the pregnancy followed by efficient and prompt treatment. The presence of
placental alpha macroglobulin-1 in the vagina specifically indicates a disruption
in the integrity of the fetal membranes and may indirectly mean increased risk
for preterm birth. Further research to properly characterize this marker and its
importance in the care of pregnant woman at risk for preterm birth is strongly
recommended.
PMID- 25845276
TI - High potassium level during pregnancy is associated with future cardiovascular
morbidity.
AB - OBJECTIVE: The present study was aimed to determine whether high potassium level
during pregnancy is an independent risk factor for future atherosclerotic
morbidity. PATIENTS AND METHODS: A case-control study was conducted including
women who delivered between the years 2000-2012 and subsequently developed
atherosclerotic morbidity after their last delivery (n = 653) and matched
controls (n = 4101). The mean follow-up duration was 57.7 +/- 36.5 and 78.5 +/-
42.3 months, respectively. The cases were further divided into: major events
(severe atherosclerotic morbidity; n = 363), minor events (i.e. cardiovascular
risk factors; n = 201) and cardiovascular evaluation tests (n = 89). The Cox
proportional hazards models were used to estimate the adjusted hazard ratios (HR)
for hospitalizations while controlling for confounders. RESULTS: A Cox
proportional hazard model, controlling for confounders such as gestational
hypertension, gestational diabetes mellitus, obesity, maternal age, creatinine
level and gestational week at index pregnancy showed that K(+ )>= 5.0 mEq/L
during pregnancy was significantly associated with hospitalizations due to severe
atherosclerotic morbidity (adjusted HR = 1.55; 95% CI 1.02-2.35; p = 0.039). A
non-significant trend was also noted with long-term total hospitalizations for
atherosclerotic (adjusted HR = 1.39; 95% CI 0.99-1.94; p = 0.052). CONCLUSION:
High potassium level during pregnancy is associated with a significant risk for
severe atherosclerotic morbidity, as it might be an indication for occult
metabolic and renal dysfunction.
PMID- 25845277
TI - Perioperative low-dose ketamine improves postoperative analgesia following
Cesarean delivery with general anesthesia.
AB - OBJECTIVE: In this study, the effect of perioperative uses of low dose ketamine
on post-operative wound pain and analgesic consumption in patients undergoing
elective Cesarean section was evaluated. METHODS: In randomized, double blind
clinical trial, 52 women with American Society of Anesthesiologists (ASA) class I
II identification undergoing elective Cesarean section in general anesthesia were
enrolled. In the ketamine group (group K), a ketamine bolus of 0.5 mg kg(-1) IV
was administered at the time of induction of general anesthesia. After induction,
a ketamine infusion of 0.25 mg kg(-1) h(-1) was started and discontinued at the
end of surgery. Patients allocated to the control group (group C) were given
identical volumes of saline. The cumulative dose of morphine consumption after
surgery was measured as the primary outcome of this study. Secondary outcomes
were pain control assessed by numeric rating scale (NRS) and need for rescue
analgesia and incidence of side effects. RESULTS: The mean 24-h morphine
consumption was lower in group K (p = 0,001). At 15 min postoperatively, NRS
values were lower in group K than group C (p = 0,001). There was no difference
among groups regarding the need for supplemental analgesia (rescue diclofenac
doses) (p > 0.05). CONCLUSIONS: Perioperative uses of low dose ketamine decreased
post-operative opioid requirements, which was observed long after the normal
expected duration of ketamine.
PMID- 25845278
TI - A Pilot Study to Compare Oxidative Status between Organically and Conventionally
Managed Dairy Cattle During the Transition Period.
AB - The aim of this study was to assess the redox balance of organically managed
dairy cattle (OMC; n = 40) during the transition period and to compare this with
conventionally managed cattle (CMC; n = 22). Serum samples of dairy cows from two
organic and one conventional farm were taken. Markers of oxidants production
[reactive oxygen species] and total serum antioxidant capacity were measured in
four different production stages: (i) far-off dry (2 to 1 months before calving;
44 samples in CMC and 48 in OMC); (ii) close-up dry (1 month until 3 days before
calving; 44 CMC; 54 OMC); (iii) fresh (3 days to +1 month after calving; 44 CMC;
49 OMC); and (iv) peak of lactation (+1 to +3 months; 71 CMC; 78 OMC). Values
were compared between production stages and against a metabolic baseline status
(4th-5th month of pregnancy; 40 CMC; 30 OMC). Our results indicated that
throughout the periparturient period, OMC had lower concentrations of reactive
oxygen species, but also a lower antioxidant capacity than CMC. Indeed, when the
two components of the redox balance were assessed together through the Oxidative
Stress index, the values of this parameter were higher for OMC than for CMC,
thereby implying a higher risk of oxidative stress. Therefore, further larger
studies are needed to confirm the current observations, as organically reared
animals might be exposed to a lack of antioxidants supply.
PMID- 25845279
TI - Predicting factors of hypoglycaemia in elderly type 2 diabetes patients:
Contributions of the GERODIAB study.
AB - The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes
(T2D) patients. Unfortunately, however, few studies are available concerning this
population. GERODIAB is a prospective, multicentre, observational study that aims
to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years
and older. After analyzing the frequency of and factors associated with
hypoglycaemia in the 6 months prior to study inclusion, it was found that
hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol
and altered mini-Geriatric Depression Scale (GDS) scores.
PMID- 25845280
TI - Three novel mutations of the ATP2C1 gene in Chinese families with Hailey-Hailey
disease.
PMID- 25845282
TI - Absolute reactivity of (N-methyl-3-pyridinium)chlorocarbene.
AB - (N-Methyl-3-pyridinium)chlorocarbene tetrafluoroborate (MePyr(+)CCl BF4(-), 4) is
generated by laser flash photolysis (LFP) of the corresponding diazirine (5) and
reacted with tetramethylethylene, cyclohexene, 1-hexene, 2-ethyl-1-butene, methyl
acrylate, and acrylonitrile. Absolute rate constants are measured for these
carbene-alkene addition reactions, and activation parameters are obtained for
additions of MePyr(+)CCl BF4(-) to tetramethylethylene, cyclohexene, and 1
hexene. MePyr(+)CCl BF4(-) is computed to be a highly reactive, electrophilic,
singlet carbene, and experiments are in accord with expectations. Its activation
parameters are compared with those of CF3CCl, CCl2, CClF, and CF2. In all cases,
enthalpy-entropy compensation is observed, with DeltaH(?) and DeltaS(?)
decreasing in tandem as carbenic stability decreases. A qualitative explanation
is offered for this phenomenon.
PMID- 25845281
TI - Discovery of new acylaminopyridines as GSK-3 inhibitors by a structure guided in
depth exploration of chemical space around a pyrrolopyridinone core.
AB - Glycogen synthase kinase-3 (GSK-3) has been proposed to play a crucial role in
the pathogenesis of many diseases including cancer, stroke, bipolar disorders,
diabetes and neurodegenerative diseases. GSK-3 inhibition has been a major area
of pharmaceutical interest over the last two decades. A plethora of reports
appeared recently on selective inhibitors and their co-crystal structures in GSK
3beta. We identified several series of promising new GSK-3beta inhibitors from a
coherent design around a pyrrolopyridinone core structure. A systematic
exploration of the chemical space around the central spacer led to potent single
digit and sub-nanomolar GSK-3beta inhibitors. When dosed orally in a transgenic
mouse model of Alzheimer's disease (AD), an exemplary compound showed significant
lowering of Tau phosphorylation at one of the GSK-3 phosphorylating sites,
Ser396. X-ray crystallography greatly aided in validating the binding hypotheses.
PMID- 25845283
TI - Risk of prostate cancer mortality in men with a history of prior cancer.
AB - OBJECTIVES: To describe outcomes of patients with prostate cancer diagnosed after
another malignancy and identify factors associated with prostate cancer death in
this population, as little is known about the clinical significance of prostate
cancer as a subsequent malignancy. PATIENTS AND METHODS: We studied 18 225 men
diagnosed with prostate cancer after another malignancy from 1973 to 2006. We
compared demographic and clinical variables, and the proportion of death from
prostate cancer vs prior malignancy with t-test and chi-squared analyses. Fine
and Gray's regression was used to consider the effect of treatment on prostate
cancer death. We then studied a second cohort of 88 013 men with prostate cancer
as a first or second malignancy to describe current diagnostic and treatment
patterns. RESULTS: One in seven men died from prostate cancer in our first
cohort. More died from prostate cancer following colorectal cancer (16.8% vs
13.7%), melanoma (13.4% vs 7.56%), and oral cancer (19.1% vs 4.04%), but fewer
following bladder cancer, kidney cancer, lung cancer, leukaemia and non-Hodgkin's
lymphoma (all P < 0.001). Prostate cancer treatment was associated with a nearly
50% lower risk of death when high-grade or high-stage (adjusted hazard ratio
0.55, 95% confidence interval [CI] 0.47-0.64). Patients who died from prostate
cancer had higher grade and stage disease, and received less treatment than
patients who died from prior malignancy. The second cohort showed subsequent
prostate cancer had more high-risk disease (36.3% vs 22.2%, P < 0.001) and less
prostate cancer treatment (adjusted odds ratio 0.872, 95% CI 0.818-0.930) than
primary prostate cancer. CONCLUSIONS: Prostate cancer remains a significant cause
of mortality when diagnosed as a subsequent cancer. These results suggest
prostate cancer treatment should be seriously considered in patients with prior
malignancies, especially those with high-grade or locally advanced prostate
cancer.
PMID- 25845289
TI - The effectiveness of conservation interventions to overcome the urban
environmental paradox.
AB - Globally, urbanization is rapidly growing cities and towns at a historically
unprecedented rate, and this rapid urban growth is influencing many facets of the
environment. This paper reviews the effectiveness of conservation interventions
that are designed to increase urban sustainability. It presents evidence for an
apparent urban-environmental paradox: while the process of urban growth converts
natural habitat to other land covers and degrades natural resources and ecosystem
function, the increase in human population can increase demand for natural
resources and ecosystem services. The fundamental problem that many conservation
interventions try to address is that most facets of the environment are common or
public goods, and are hence undervalued in decision making (market failure). The
paper presents a threefold classification of conservation interventions in
cities: conservation in the city (protecting biodiversity), conservation by the
city (reducing per capita resource and energy use), and conservation for cities
(projects that maintain or enhance ecosystem services). It ends by discussing
methods for spatially targeting conservation interventions of all three types and
for quantifying the effectiveness of interventions retrospectively.
PMID- 25845290
TI - Prime-boost vaccination strategy with bacillus Calmette-Guerin (BCG) and
liposomized alpha-crystalline protein 1 reinvigorates BCG potency.
AB - Bacillus Calmette-Guerin (BCG) remains the only available and most widely
administered vaccine against Mycobacterium tuberculosis (Mtb), yet it fails to
protect vaccinated individuals either from primary infection or reactivation of
latent tuberculosis (TB). Despite BCG's variable efficacy against TB, the fact
remains that BCG imparts protection in children against the disease, indicating
that BCG possesses a wide protective antigenic repertoire. However, its failure
to impart protection in adulthood can be linked to its failure to generate long
lived memory response and elicitation of an inadequate immune response against
latency-associated antigens. Therefore, to improve the protective efficacy of
BCG, a novel vaccination strategy is required. Consequently, in the present
study, we have exploited the vaccination potential of liposomized alpha
crystalline 1 (Acr1L), a latency-associated antigen to induce enduring protective
immunity against Mtb in BCG-primed animals. It is noteworthy that an increase in
the multi-functional [interferon (IFN)-gamma(hi) /tumour necrosis factor (TNF)
alpha(hi) ] CD4 and CD8 T cells were observed in BCG-primed and Acr1L-boosted
(BCG-Acr1L) animals, compared to BCG alone. Further, substantial expansion of
both central memory (CD44(hi) /CD62L(hi) ) and effector memory (CD44(hi)
/CD62L(lo) ) populations of CD4 and CD8 T cells was noted. Importantly, BCG-Acr1L
exhibited significantly better protection than BCG, as evidenced by a reduction
in the bacterial burden and histopathological data of the lungs. In essence, BCG
Acr1L could be a potent future vaccination strategy to reinvigorate BCG potency.
PMID- 25845291
TI - The Kings Score refines prognostic prediction in hepatocellular carcinoma: a
novel application.
AB - BACKGROUND & AIMS: There are a number of prognostic scores in hepatocellular
carcinoma (HCC), none of which is optimal in predicting overall survival (OS) in
the individual patient, particularly in intermediate stage disease, where
patients are not surgically treatable but may qualify for a wide range of
palliative interventions. We evaluated the prognostic role of a biochemical
algorithm, the Kings Score (KS), in the palliative setting of care. METHODS: We
used the algorithm [age x AST x INR]/platelet count to derive the KS. Full
clinical data including Barcelona Clinic Liver Cancer (BCLC) stage were studied
in a training set of 97 patients from the UK. Independent predictors of survival
identified in multivariate analysis were validated in an independent cohort of
766 patients from Japan and Italy. RESULTS: In both training and validation sets,
KS was confirmed as an independent predictor of OS (P < 0.01). Ad-hoc subgroup
analysis revealed the KS to be prognostic in the palliative setting, being able
to subclassify patients presenting with intermediate and advanced disease
according to BCLC criteria (P < 0.001). CONCLUSION: The KS integrates into the
BCLC system to improve prognostic substratification in the palliative setting of
care. The KS may help reducing disease heterogeneity and refine treatment
allocation in intermediate-advanced HCC.
PMID- 25845292
TI - Integrated whole-genome screening for Pseudomonas aeruginosa virulence genes
using multiple disease models reveals that pathogenicity is host specific.
AB - Pseudomonas aeruginosa is a multi-host opportunistic pathogen causing a wide
range of diseases because of the armoury of virulence factors it produces, and it
is difficult to eradicate because of its intrinsic resistance to antibiotics.
Using an integrated whole-genome approach, we searched for P. aeruginosa
virulence genes with multi-host relevance. We constructed a random library of 57
360 Tn5 mutants in P. aeruginosa PAO1-L and screened it in vitro for those
showing pleiotropic effects in virulence phenotypes (reduced swarming, exo
protease and pyocyanin production). A set of these pleiotropic mutants were
assayed for reduced toxicity in Drosophila melanogaster, Caenorhabditis elegans,
human cell lines and mice. Surprisingly, the screening revealed that the
virulence of the majority of P. aeruginosa mutants varied between disease models,
suggesting that virulence is dependent on the disease model used and hence the
host environment. Genomic analysis revealed that these virulence-related genes
encoded proteins from almost all functional classes, which were conserved among
P. aeruginosa strains. Thus, we provide strong evidence that although P.
aeruginosa is capable of infecting a wide range of hosts, many of its virulence
determinants are host specific. These findings have important implication when
searching for novel anti-virulence targets to develop new treatments against P.
aeruginosa.
PMID- 25845293
TI - Serum biochemistry reference intervals of live wild dugongs (Dugong dugon) from
urban coastal Australia.
AB - BACKGROUND: Little is known about the baseline clinical pathology of the dugong
(Dugong dugon), a vulnerable marine mammal found in tropical coastal marine
systems. OBJECTIVES: The purpose of the study was to collect and determine
reference intervals (RI) for select serum biochemical variables for dugongs, and
to analyze differences between males and females and different age groups.
METHODS: Reference intervals were established from 103 apparently healthy, wild
caught dugongs for 31 analytes using a Beckman Coulter AU400 Automated Chemistry
Analyzer and an Olympus AU680 Chemistry-Immuno Analyzer. RESULTS: Significant
differences (P < .05) in some of the variables were found related to size class,
sex, and pregnancy status. Adult dugongs had higher serum sodium, potassium,
bicarbonate, glucose, and l-lactate concentrations and higher anion gap, compared
to sub-adults. Male dugongs had higher triglyceride and l-lactate concentrations
than females. Pregnant females displayed higher l-lactate levels compared to
nonpregnant animals. Statistical differences in variables within the population
contributed to better understanding of the physiologic differences between
cohorts. Some serum biochemistry changes observed in this study here also
potentially include some effects of pursuit on dugongs (eg, higher l-lactate);
however, as all dugongs were subject to similar capture and handling, serum
biochemistry RI should be considered as normal for captured dugongs. CONCLUSIONS:
The serum biochemical RI documented here are considered representative of a
population of healthy captured dugongs. They provide a baseline for health
surveillance of this and other dugong populations.
PMID- 25845294
TI - Pathophysiology and treatment of typical and atypical hemolytic uremic syndrome.
AB - Hemolytic uremic syndrome is a rare disease, frequently responsible for renal
insufficiency in children. Recent findings have led to renewed interest in this
pathology. The discovery of new gene mutations in the atypical form of HUS and
the experimental data suggesting the involvement of the complement pathway in the
typical form, open new perspectives for treatment. This review summarizes the
current state of knowledge on both typical and atypical hemolytic uremic syndrome
pathophysiology and examines new perspectives for treatment.
PMID- 25845295
TI - Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior
ciliary arteries.
AB - In the present study, we investigate the inhibitory effect of novel H2S donors,
AP67 and AP72 on isolated bovine posterior ciliary arteries (PCAs) under
conditions of tone induced by an adrenoceptor agonist. Furthermore, we examined
the possible mechanisms underlying the AP67- and AP72-induced relaxations.
Isolated bovine PCA were set up for measurement of isometric tension in organ
baths containing oxygenated Krebs solution. The relaxant action of H2S donors was
studied on phenylephrine-induced tone in the absence or presence of enzyme
inhibitors for the following pathways: cyclooxygenase (COX); H2S; nitric oxide
and the ATP-sensitive K(+) (KATP) channel. The H2S donors, NaSH (1 nM - 10 MUM),
AP67 (1 nM - 10 MUM) and AP72 (10 nM - 1 MUM) elicited a concentration-dependent
relaxation of phenylephrine-induced tone in isolated bovine PCA. While the COX
inhibitor, flurbiprofen (3 MUM) blocked significantly (p < 0.05) the inhibitory
response elicited by AP67, it had no effect on relaxations induced by NaSH and
AP72. Both aminooxyacetic acid (30 MUM) and propargylglycine (1 mM), enzyme
inhibitors of H2S biosynthesis caused significant (p < 0.05) rightward shifts in
the concentration-response curve to AP67 and AP72. Furthermore, the KATP channel
antagonist, glibenclamide (300 MUM) and the NO synthase inhibitor, l-NAME (100
MUM) significantly attenuated (p < 0.05) the relaxation effect induced by AP67
and AP72 on PCA. We conclude that H2S donors can relax pre-contracted isolated
bovine PCA, an effect dependent on endogenous production of H2S. The inhibitory
action of only AP67 on pre-contracted PCA may involve the production of
inhibitory endogenous prostanoids. Furthermore, the observed inhibitory action of
H2S donors on PCA may depend on the endogenous biosynthesis of NO and by an
action of KATP channels.
PMID- 25845296
TI - Pediatric Cutaneous Nontuberculous Mycobacterium Infections in Singapore.
AB - BACKGROUND: Nontuberculous mycobacterium (NTM) infections are rare in children,
with limited published studies. The course of the disease can be variable and
there are no accepted treatment guidelines for the management of NTM infections
in children. OBJECTIVE: To review a cohort of pediatric patients admitted to a
tertiary pediatric hospital in Singapore for cutaneous NTM infections. METHODS: A
retrospective review was performed of all children admitted to KK Women's and
Children's Hospital with cutaneous NTM infections from 2002 to 2012. RESULTS:
Sixty-seven patients with positive NTM cultures from various body sites were
identified. Eight of the 67 patients (11.9%) presented with cutaneous NTM without
evidence of systemic involvement. The mean age at diagnosis for these eight
patients was 10 years (range 5-21 yrs). Mycobacterium abscessus was the most
common NTM isolated (five patients), followed by Mycobacterium hemophilium (two
patients) and Mycobacterium kansasii (one patient). Most patients presented with
isolated skin abscesses. Two patients were immunocompromised. Six patients
required multidrug antibiotic treatment for a median duration of 5.5 months
(range 3-17 mos). The median follow-up duration was 8.5 months (range 2 wks-29
mos). CONCLUSION: Although the incidence of cutaneous NTM is rare, the diagnosis
should be considered in patients presenting with chronic wounds. Most patients
require treatment with multidrug antibiotic therapy, although uncomplicated
abscesses can be treated with surgical incision and drainage alone.
PMID- 25845297
TI - Management of diabetic nephropathy: Recent progress and future perspective.
AB - Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD)
affecting ~20-30% diabetics, is associated with increased cardiovascular
mortality. The progression of kidney disease in patients with diabetes can take
many years. It occurs as a result of interaction between both genetic and
environmental factors in individuals with both type 1 and type 2 diabetes.
Hyperglycaemia, hypertension, and genetic pre-disposition are the main risk
factors besides elevated serum lipids, smoking habits, and the amount of dietary
proteins. Interventions such as glycaemic control, blood pressure control and
inhibition of the renin-angiotensin-aldosterone system have been shown to slow
this progression. Despite the implementation of these strategies, the number of
patients with diabetes that ultimately develop end-stage renal disease remains
high. The treatment of DN, therefore, has posed a formidable challenge besides
optimization of renin-angiotensin-aldosterone system blockade in patients with
DN; additional investigation has focused on the potential of novel therapies that
target various pathways upregulated by hyperglycaemia or other targets believed
to promote the progression of DN such as oxidative stress, inflammation,
endothelin system and vitamin D receptors. This review article addresses the
pathogenesis and some of the well established principles regarding the
progression and accepted management of DN, and also includes the perspectives of
novel anti-DN agents and the future directions for the prevention of DN.
PMID- 25845298
TI - Multiparametric characterisation of neuronal network activity for in vitro
agrochemical neurotoxicity assessment.
AB - The last few decades have seen the marketing of hundreds of new pesticide
products with a forecasted expansion of the global agrochemical industry. As
several pesticides directly target nervous tissue as their mechanism of toxicity,
alternative methods to routine in vivo animal testing, such as the Multi
Electrode Array (MEAs)-based approach, have been proposed as an in vitro tool to
perform sensitive, quick and low cost neuro-toxicological screening. Here, we
examined the effects of a training set of eleven active substances known to have
neuronal or non-neuronal targets, contained in the most commonly used
agrochemicals, on the spontaneous electrical activity of cortical neuronal
networks grown on MEAs. A multiparametric characterisation of neuronal network
firing and bursting was performed with the aim of investigating how this can
contribute to the efficient evaluation of in vitro chemical-induced
neurotoxicity. The analysis of MFR, MBR, MBD, MISI_B and % Spikes_B parameters
identified four different groups of chemicals: one wherein only inhibition is
observed (chlorpyrifos, deltamethrin, orysastrobin, dimoxystrobin); a second one
in which all parameters, except the MISI_B, are inhibited (carbaryl, quinmerac);
a third in which increases at low chemical concentration are followed by
decreases at high concentration, with exception of MISI_B that only decreased
(fipronil); a fourth in which no effects are observed (paraquat, glyphosate,
imidacloprid, mepiquat). The overall results demonstrated that the
multiparametric description of the neuronal networks activity makes MEA-based
screening platform an accurate and consistent tool for the evaluation of the
toxic potential of chemicals. In particular, among the bursting parameters the
MISI_B was the best that correlates with potency and may help to better define
chemical toxicity when MFR is affected only at relatively high concentration.
PMID- 25845299
TI - Potential of casein as a nutrient intervention to alleviate lead (Pb) acetate
mediated oxidative stress and neurotoxicity: First evidence in Drosophila
melanogaster.
AB - Understanding the interaction between dietary protein deficits and neurotoxicants
such as lead (Pb) is critical since oxidative stress is a common denominator
under such conditions. The Drosophila system is an extensively used model to
investigate the interaction between nutrients and environmental toxicants.
Accordingly, we have examined the hypothesis that casein (CSN) enrichment has the
propensity to attenuate Pb-associated phenotype, oxidative stress and
neurotoxicity in Drosophila melanogaster. Exposure of young (2-3 d) and adult
flies (10-12 d old) to Pb acetate (0-20 mM, 7 d) in the medium resulted in a
concentration dependent mortality and the survivors exhibited a hyperactive
phenotype. While males showed higher susceptibility to Pb among both age groups,
young flies were relatively more susceptible than adults. Pb exposure (5-10 mM, 5
d) among young flies caused robust oxidative stress as evidenced by markedly
elevated levels of reactive oxygen species with concomitant perturbations in the
activities of antioxidant enzymes (diminished SOD and elevated thioredoxin
reductase) and altered redox state. Further, Pb caused significant elevation in
the activity of acetylcholinesterase and dopamine levels. In a satellite study,
we assessed the modulatory effect of CSN-enriched diet (1-2%) on Pb intoxication
in terms of lethality, hyperactivity, oxidative stress and neurotoxicity. CSN
markedly offset Pb-induced lethality and diminished the hyperactivity response.
While CSN enrichment among Pb (5 mM) treated flies caused further elevation in
ROS levels and thioredoxin reductase activity, the SOD levels were restored to
normalcy. Further, CSN improved the activity levels of complex I-III and restored
the dopamine levels. Our data suggest that Pb-induced toxicity in the Drosophila
system may be predominantly mediated through oxidative stress mechanisms and the
propensity of casein-enriched diet to abrogate such responses. Hence, we propose
that enrichment of diet with protein such as casein may be a useful approach to
alleviate Pb associated adverse effects in children.
PMID- 25845301
TI - Synthesis of dithienogermole-containing oligo- and polysilsesquioxanes as
luminescent materials.
AB - Dithienogermole (DTG)-containing oligo- and polysilsesquioxanes were prepared by
hydrolysis/condensation of DTGs bearing one () or two trialkoxysilyl group(s) ().
The reaction of gave a cage-type octasilsesquioxane with eight DTG groups at the
edges () as a viscous oil, whereas the reaction of yielded a network polymer ()
as a self-standing film. showed a photoluminescence (PL) quantum yield (Phi) of
56% in THF. This value was as high as that of (Phi = 58%), in spite of the
accumulation of DTG units in the molecule, as characteristics of the POSS
structure. The PL of in THF was suppressed by contact with nitrobenzene, showing
the potential of for sensing nitroaromatic explosives. Polymer exhibited a
relatively low Phi of 2% as a film, but Phi was improved to 38% by
copolymerization with trimethoxymethylsilane. was also copolymerized with a
trimethoxysilyl-substituted carbazole derivative () to provide
polysilsesquioxanes with DTG and carbazole units, which showed efficient photo
energy transfer from carbazole to DTG in the films. Similar copolymerization of
with in the presence of poly(9-vinylcarbazole) provided a composite material with
hole-transporting electroluminescence properties, applicable in multi-layered
organic light emitting diodes.
PMID- 25845300
TI - Allopurinol reduces severity of delayed neurologic sequelae in experimental
carbon monoxide toxicity in rats.
AB - Approximately half of those who survive severe carbon monoxide (CO) poisoning
develop delayed neurologic sequelae. Growing evidence supports the crucial role
of free radicals in delayed brain injury associated with CO toxicity. Xanthine
oxidase (XO) has been reported to play a pivotal role in the generation of
reactive oxygen species (ROS) in CO poisoning. A recent report indicates that
allopurinol both attenuated oxidative stress and possessed anti-inflammatory
properties in an animal model of acute liver failure. In this study, we aimed to
explore the potential of allopurinol to reduce the severity of delayed neurologic
sequelae. The rats were first exposed to 1000 ppm CO for 40 min and then to 3000
ppm CO for another 20 min. Following CO poisoning, the rats were injected with
allopurinol (50 mg/kg, i.p.) six times. Results showed that allopurinol
significantly reduced neuronal death and suppressed expression of pro
inflammatory factors, including tumor necrosis factor-alpha, intercellular
adhesion molecule-1, ionized calcium-binding adapter molecule 1, and degraded
myelin basic protein. Furthermore, behavioral studies revealed an improved
performance in the Morris water maze test. Our findings indicated that
allopurinol may have protective effects against delayed neurologic sequelae
caused by CO toxicity.
PMID- 25845302
TI - A prospective randomised trial comparing mesh types and fixation in totally
extraperitoneal inguinal hernia repairs.
AB - The totally extraperitoneal (TEP) approach for surgical repair of inguinal
hernias has emerged as a popular technique. We conducted a prospective randomised
trial to compare patient comfort scores using different mesh types and fixation
using this technique. Over a 14 month period, 146 patients underwent 232 TEP
inguinal hernia repairs. We compared the comfort scores of patients who underwent
these procedures using different types of mesh and fixation. A non-absorbable 15
* 10 cm anatomical mesh fixed with absorbable tacks (Control group) was compared
with either a non-absorbable 15 * 10 cm folding slit mesh with absorbable tacks
(Group 2), a partially-absorbable 15 * 10 cm mesh with absorbable tacks (Group 3)
or a non-absorbable 15 * 10 cm anatomical mesh fixed with 2 ml fibrin sealant
(Group 4). Outcomes were compared at 1, 2, 4 and 12 weeks using the Carolina
Comfort Scale (CCS) scores. At 1, 2, 4 and 12 weeks, the median global CCS scores
were low for all treatment groups. Statistically significant differences were
seen only for median CCS scores and subscores with the use of partially
absorbable mesh with absorbable tacks (Group 3) at weeks 2 and 4. However, these
were no longer significant at week 12. In this study, the TEP inguinal hernia
repair with minimal fixation results in low CCS scores. There were no statistical
differences in CCS scores when comparing types of mesh, configuration of the mesh
or fixation methods.
PMID- 25845303
TI - The obesity-related FTO gene variant associates with the risk of recurrent
miscarriage.
AB - OBJECTIVE: To investigate the association of the fat mass and obesity associated
gene (FTO) rs9939609 single nucleotide polymorphism with recurrent miscarriage.
DESIGN: Candidate gene association study. SETTING: Human Genetics Unit, Colombo,
Sri Lanka. POPULATION: A total of 202 Sinhalese women with two or more first
trimester miscarriages and no living children (cases) and 202 age- and ethnicity
matched women with no history of miscarriage and having two or more living
children (controls). METHODS: Peripheral blood was collected from the
participants and DNA was extracted. Genotyping was performed at the Australian
genome Research Facility using the Sequenom MassARRAY system. Genotype and allele
frequencies of cases were compared with controls using chi-squared testing. MAIN
OUTCOME MEASURES: The prevalence of the single nucleotide polymorphism in cases
and controls. RESULTS: The mean age of the women in the recurrent miscarriage
group was 31.9 +/- 0.4 years and that of the control group was 32.3 +/- 0.3
years. Of the women in the recurrent miscarriage group, 140 (69.3%) had
experienced three or more first-trimester miscarriages. The prevalence of the AA
genotype [p = 0.0002, odds ratio (95% CI) = 3.8 (1.8-8.0)] and A allele [p =
0.002, odds ratio (95% CI) = 1.6 (1.2-2.2)] of the FTO rs9939609 single
nucleotide polymorphism were increased in women in the recurrent miscarriage
group compared with the control group. CONCLUSION: The obesity-related FTO
rs9939609 single nucleotide polymorphism associates with recurrent miscarriage.
This finding warrants further investigation with controlling for important
factors such as body mass index, diabetes and cardiovascular disease status. The
single nucleotide polymorphism may be useful in predicting the risk of recurrent
miscarriage.
PMID- 25845304
TI - Engineering biological systems toward a sustainable bioeconomy.
AB - The nature of our major global risks calls for sustainable innovations to
decouple economic growth from greenhouse gases emission. The development of
sustainable technologies has been negatively impacted by several factors
including sugar production costs, production scale, economic crises, hydraulic
fracking development and the market inability to capture externality costs.
However, advances in engineering of biological systems allow bridging the gap
between exponential growth of knowledge about biology and the creation of
sustainable value chains for a broad range of economic sectors. Additionally,
industrial symbiosis of different biobased technologies can increase
competitiveness and sustainability, leading to the development of eco-industrial
parks. Reliable policies for carbon pricing and revenue reinvestments in
disruptive technologies and in the deployment of eco-industrial parks could boost
the welfare while addressing our major global risks toward the transition from a
fossil to a biobased economy.
PMID- 25845305
TI - Deletion of hxk1 gene results in derepression of xylose utilization in
Scheffersomyces stipitis.
AB - A major problem in fermenting xylose in lignocellulosic substrates is the
presence of glucose and mannose which inhibit xylose utilization. Previous
studies showed that catabolite repression in some yeasts is associated with
hexokinases and that deletion of one of these gene(s) could result in derepressed
mutant strain(s). In this study, the hxk1 encoding hexokinase 1 in
Scheffersomyces stipitis was disrupted. The ?hxk1 SS6 strain retained the ability
to utilize the main hexoses and pentoses commonly found in lignocellulosic
hydrolysates as efficiently as the wild-type (WT) strain. SS6 also fermented the
dominant sugars to ethanol; however, on xylose, the ?hxk1 strain produced more
xylitol and less ethanol than the WT. On mixed sugars, as expected the WT
utilized glucose ahead of xylose and xylose utilization did not commence until
all the glucose was consumed. In contrast, the ?hxk1 mutant showed derepression
in that it started to utilize xylose even when considerable glucose (about 1.72%,
w/v) remained in the medium. Similarly, mannose did not repress xylose
utilization by the ?hxk1 mutant and xylose and mannose were simultaneously
utilized. The results are of interest in efforts to engineer yeast strains
capable of efficiently utilizing glucose and xylose simultaneously for
lignocellulosic biomass conversion.
PMID- 25845306
TI - Investigating the influence of long-range transport on surface O3 in Nevada, USA,
using observations from multiple measurement platforms.
AB - The current United States (US) National Ambient Air Quality Standard (NAAQS) for
O3 (75 ppb) is expected to be revised to between 60 and 70 ppb. As the NAAQS
becomes more stringent, characterizing the extent of O3 and precursors
transported into the US is increasingly important. Given the high elevation,
complex terrain, and location in the Intermountain West, the State of Nevada is
ideally situated to intercept air transported into the US. Until recently,
measurements of O3 and associated pollutants were limited to areas in and around
the cities of Las Vegas and Reno. In 2011, the Nevada Rural Ozone Initiative
began and through this project 13 surface monitoring sites were established. Also
in 2011, the NASA Ames Alpha Jet Atmospheric eXperiment (AJAX) began making
routine aircraft measurements of O3 and other greenhouse gases in Nevada. The
availability of aircraft and surface measurements in a relatively rural, remote
setting in the Intermountain West presented a unique opportunity to investigate
sources contributing to the O3 observed in Nevada. Our analyses indicate that
stratosphere to troposphere transport, long-range transport of Asian pollution,
and regional emissions from urban areas and wildfires influence surface
observations. The complexity of sources identified here along with the fact that
O3 frequently approaches the threshold being considered for a revised NAAQS
indicate that interstate and international cooperation will be necessary to
achieve compliance with a more stringent regulatory standard. Further, on a
seasonal basis we found no significant difference between daily 1-h maximum O3 at
surface sites, which ranged in elevation from 888 to 2307 m, and aircraft
measurements of O3 <2500 m which suggests that similar processes influence
daytime O3 across rural Nevada and indicates that column measurements from
Railroad Valley, NV are useful in understanding these processes.
PMID- 25845307
TI - Management of acne vulgaris with hormonal therapies in adult female patients.
AB - Acne vulgaris is a very common condition affecting up of 93% of adolescents.
Although rare, this disease may persist in adulthood. In adult women with acne
(those older than 25 years old), this condition is particularly relevant because
of the refractory to conventional therapies, which makes acne a challenge for
dermatologists in this group of patients. In order to its potential risk for
chronicity and the involvement of visible anatomical sites such as face and upper
torso, acne has been associated with a wide spectrum of psychological and social
dysfunction such as depression, anxiety, suicidal ideation, somatization, and
social inhibition. In particular, adult women with acne have been shown to be
adversely impacted by the effect of acne on their quality of life. For the last
four decades, dermatologists have used hormonal therapies for the management of
acne vulgaris in adult women, which are considered a rational choice given the
severity and chronicity of this condition in this group of patients. The aim of
this work is to review the hormonal drugs for management of acne.
PMID- 25845308
TI - The performance of three mortality risk-adjustment comorbidity indices in a
community epilepsy cohort.
AB - Mortality risk-adjustment comorbidity indices are an efficient means of
controlling for the important confounding effect of somatic and psychiatric
comorbidities in observational mortality studies. We carried out an external
validation study and compared the performance of the Charlson, Elixhauser and
Epilepsy-specific (ES) indices using the National General Practice Study of
Epilepsy, a community-based prospective cohort of 558 people with incident
epilepsy followed for 23.3 years (median). The minimum and maximum crude
mortality rates were similar between the three indices, but mid-range Elixhauser
scores predicted lower rates relative to the two other indices. Two of the
stratified Charlson Kaplan-Meier survival probability curves crossed, and a low
Elixhauser score was associated with a counterintuitive increase in mortality.
Each comorbidity index was a significant predictor of mortality in the Cox
proportional hazards models, although there was evidence that the unadjusted
Charlson regression model violated the proportionality assumption. Harrell's c
statistics were >0.87 in all adjusted models. All three indices performed well,
but there is evidence that the ES index may be more discriminating and have a
better model fit than the Charlson or Elixhauser indices in a community-based
clinical cohort of people with epilepsy.
PMID- 25845309
TI - Biophysical characterization of KV3.1 potassium channel activating compounds.
AB - The effect of two positive modulators, RE1 and EX15, on the voltage-gated K(+)
channel Kv3.1 was investigated using the whole-cell patch-clamp technique on
HEK293 cells expressing Kv3.1a. RE1 and EX15 increased the Kv3.1 currents in a
concentration-dependent manner with an EC50 value of 4.5 and 1.3uM, respectively.
However, high compound concentrations caused an inhibition of the Kv3.1 current.
The compound-induced activation of Kv3.1 channels showed a profound
hyperpolarized shift in activation kinetics. 30uM RE1 shifted V1/2 from 5.63+/
0.31mV to -9.71+/-1.00mV and 10uM EX15 induced a shift from 10.77+/-0.32mV to
15.11+/-1.57mV. The activation time constant (Tauact) was reduced for both RE1
and EX15, with RE1 being the fastest activator. The deactivation time constant
(Taudeact) was also markedly reduced for both RE1 and EX15, with EX15 inducing
the most prominent effect. Furthermore, subjected to depolarizing pulses at 30Hz,
both compounds were showing a use-dependent effect resulting in a reduction of
the compound-mediated effect. However, during these conditions, RE1- and EX15
modified current amplitudes still exceeded the control condition amplitudes by up
to 200%. In summary, the present study introduces the first detailed biophysical
characterization of two new Kv3.1 channel modifying compounds with different
modulating properties.
PMID- 25845310
TI - Simultaneous Synchrotron WAXD and Fast Scanning (Chip) Calorimetry: On the
(Isothermal) Crystallization of HDPE and PA11 at High Supercoolings and Cooling
Rates up to 200 degrees C s(-1).
AB - An experimental setup, making use of a Flash DSC 1 prototype, is presented in
which materials can be studied simultaneously by fast scanning calorimetry (FSC)
and synchrotron wide angle X-ray diffraction (WAXD). Accumulation of multiple,
identical measurements results in high quality, millisecond WAXD patterns.
Patterns at every degree during the crystallization and melting of high density
polyethylene at FSC typical scanning rates from 20 up to 200 degrees C s(-1) are
discussed in terms of the temperature and scanning rate dependent material
crystallinities and crystal densities. Interestingly, the combined approach
reveals FSC thermal lag issues, for which can be corrected. For polyamide 11,
isothermal solidification at high supercooling yields a mesomorphic phase in less
than a second, whereas at very low supercooling crystals are obtained. At
intermediate supercooling, mixtures of mesomorphic and crystalline material are
generated at a ratio proportional to the supercooling. This ratio is constant
over the isothermal solidification time.
PMID- 25845311
TI - Polarized trafficking provides spatial cues for planar cell polarization within a
tissue.
AB - Planar cell polarity, the polarization of cells within the plane of the
epithelium, orthogonal to the apical-basal axis, is essential for a growing list
of developmental events, and - over the last 15 years - has evolved from a little
studied curiosity in Drosophila to the subject of a substantial research
enterprise. In that time, it has been recognized that two molecular systems are
responsible for polarization of most tissues: Both the "core" Frizzled system and
the "global" Fat/Dachsous/Four-jointed system produce molecular asymmetry within
cells, and contribute to morphological polarization. In this review, we discuss
recent findings on the molecular mechanism that links "global" directional
signals with local coordinated polarity.
PMID- 25845312
TI - Persistence of poor sleep predicts the severity of the clinical condition after
6months of standard treatment in patients with eating disorders.
AB - Clinical evidence suggests that eating disorder (ED) patients experience poor
sleep even if they rarely complain of it. However, direct empirical evidence
supporting this relationship is still sparse. In order to provide direct
evidence, poor sleep, severity of the ED symptoms and depression were obtained in
562 ED patients at treatment admission (T0). For 271 patients out of them, data
were also available after 6months of standard treatment (T1). Results evidence
that at T0 poor sleep predicts severity of ED symptoms through the mediation of
depression. Persistence of poor sleep at T1 directly predicts the severity of the
ED symptoms both directly and through the mediation of depression. These findings
suggest that the treatment of ED may benefit from addressing poor sleep since its
presence and persistence increase comorbidity and attrition to the standard
treatment.
PMID- 25845313
TI - Neurotoxicity of cerebro-spinal fluid from patients with Parkinson's disease on
mesencephalic primary cultures as an in vitro model of dopaminergic neurons.
AB - Parkinson's disease is a degenerative disorder of the central nervous system. In
spite of extensive research, neither the cause nor the mechanisms have been
firmly established thus far. One assumption is that certain toxic substances may
exist in the cerebro-spinal fluid (CSF) of Parkinson's disease patients. To
confirm the neurotoxicity of CSF and study the potential correlation between
neurotoxicity and the severity of Parkinson's disease, CSF was added to cultured
cells. By observation of cell morphology, changes in the levels of lactate
dehydrogenase, the ratio of tyrosine hydroxylase-positive cells, and the
expression of tyrosine hydroxylase mRNA and protein, the differences between the
two groups were shown. The created in vitro model of dopaminergic neurons using
primary culture of mouse embryonic mesencephalic tissue is suitable for the study
of neurotoxicity. The observations of the present study indicated that CSF from
Parkinson's disease patients contains factors that can cause specific injury to
cultured dopaminergic neurons. However, no obvious correlation was found between
the neurotoxicity of CSF and the severity of Parkinson's disease.
PMID- 25845314
TI - Association between suicidal ideation and exposure to suicide in social
relationships among family, friend, and acquaintance survivors in South Korea.
AB - Exposure to suicide in social relationships may be associated with suicidal
ideation among survivors. In South Korea, which is known for having the highest
suicide rate among OECD countries, exposure to suicide in social relationships
can have serious consequences as social relationships are greatly emphasized in
the society. The purpose of this study was to examine the association between
survivors' suicidal ideation and their exposure to suicide in close
relationships. Data collected through a telephone survey of a total of 1,000 men
and women selected from across the nation using a stratified sampling method were
analyzed. The results show that individuals who lost a family member, friend, or
acquaintance in their lifetime are 4.5 times, 3.7 times, 2.2 times, respectively,
more likely to have suicidal ideation in the past year compared to those without
such experience. These findings suggest that special intervention for suicide
survivors should be considered for those who experience suicide in close
relationships.
PMID- 25845315
TI - Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled
Drugs.
AB - During the last decades, the importance of modeling and simulation in clinical
drug development, with the goal to qualitatively and quantitatively assess and
understand mechanisms of pharmacokinetic processes, has strongly increased.
However, this increase could not equally be observed for orally inhaled drugs.
The objectives of this review are to understand the reasons for this gap and to
demonstrate the opportunities that mathematical modeling of pharmacokinetics of
orally inhaled drugs offers. To achieve these objectives, this review (i)
discusses pulmonary physiological processes and their impact on the
pharmacokinetics after drug inhalation, (ii) provides a comprehensive overview of
published pharmacokinetic models, (iii) categorizes these models into
physiologically based pharmacokinetic (PBPK) and (clinical data-derived)
empirical models, (iv) explores both their (mechanistic) plausibility, and (v)
addresses critical aspects of different pharmacometric approaches pertinent for
drug inhalation. In summary, pulmonary deposition, dissolution, and absorption
are highly complex processes and may represent the major challenge for modeling
and simulation of PK after oral drug inhalation. Challenges in relating systemic
pharmacokinetics with pulmonary efficacy may be another factor contributing to
the limited number of existing pharmacokinetic models for orally inhaled drugs.
Investigations comprising in vitro experiments, clinical studies, and more
sophisticated mathematical approaches are considered to be necessary for
elucidating these highly complex pulmonary processes. With this additional
knowledge, the PBPK approach might gain additional attractiveness. Currently,
(semi-)mechanistic modeling offers an alternative to generate and investigate
hypotheses and to more mechanistically understand the pulmonary and systemic
pharmacokinetics after oral drug inhalation including the impact of pulmonary
diseases.
PMID- 25845316
TI - Relevance of using a compressive preload in the cervical spine: an experimental
and numerical simulating investigation.
AB - Simulating compressive action of muscles, a follower load attends to reproduce a
more physiological biomechanical behaviour of the cervical spine. Only few
experimental studies reported its influence on kinematics and intradiscal
pressure in the cervical spine. STUDY DESIGN: In vitro human cadaveric and
numerical simulating evaluation of a compressive preload in the cervical spine.
OBJECTIVES: To analyse the influence of a compressive follower preload on the
biomechanical behaviour of the cervical spine. METHODS: The present study was
divided into two parts: part 1: in vitro investigation; part 2: numerical
simulating analysis. Part 1: Twelve human cadaveric spines from C2 to T2 were
evaluated intact and after application of a 50-N follower load. All tests were
performed under load control by applying pure moments loading of 2 Nm in
flexion/extension (FE), axial rotation (AR) and lateral bending (LB). Three
dimensional displacements were measured using an optoelectronic system, and
intradiscal pressures were measured at two levels. Part 2: Using a 3D finite
element model, we evaluated the influence of a 50- and 100-N compressive preload
on intradiscal loads, facets forces and ranges of motion. Different positions of
the follower load along the anteroposterior axis (+/-5 mm) were also simulated.
RESULTS: Part 1: Mean variation of cervical lordosis was 5 degrees +/- 3 degrees
. The ROM slightly increased in FE, whereas it consistently decreased in AR and
LB. Coupled lateral bending during AR was also reduced. Increase in hysteresis
was observed on load-displacement curves only for AR and LB. Intradiscal
pressures increased, but the aspect of load-pressure curves was altered in AR and
LB. Part 2: Using the FE model, only minimal changes in ROM were noted following
the simulation of a 50-N compressive load for the three loading conditions.
Compared to intact condition, <10% variation was observed with regard to the
different magnitude and positioning simulated. Intradiscal loads and facets
forces were systematically increased by applying compressive preload.
CONCLUSIONS: Although the follower load represents an attractive option to apply
compressive preload during experimental tests, we found that this method could
affect the native biomechanical behaviour of spine specimen depending on which
movement was considered. Only minimal effects were observed in FE, whereas
significant changes in kinematics and intradiscal pressures were observed for AR
and LB.
PMID- 25845317
TI - [Genetic diversity and immunological characteristics of malignant melanoma: the
therapeutic spectrum].
AB - Malignant melanoma, originating from pigment cells, is a highly aggressive tumour
affecting patients of any age group. Its incidence is rapidly growing. The most
common form can be easily diagnosed by any physician. There are some well-known
genetic (skin-, eye-, hair colour, naevi, melanoma in the personal/family
history) and environmental (ultraviolet radiation) predisposing factors.
Treatment is based on early diagnosis and excision. When metastasis occurs, the
traditional chemo- and radiotherapy gives a low response rate. Recently some
newly approved targeted therapies and immunomodulant drugs have become available.
This review focuses on the classification and novel therapeutic approaches of
malignant melanoma to provide guidance to clinicians.
PMID- 25845318
TI - [Prognostic value of absolute monocyte count in chronic lymphocytic leukaemia].
AB - INTRODUCTION: The low peripheral absolute lymphocyte and high monocyte count have
been reported to correlate with poor clinical outcome in various lymphomas and
other cancers. However, a few data known about the prognostic value of absolute
monocyte count in chronic lymphocytic leukaemia. AIM: The aim of the authors was
to investigate the impact of absolute monocyte count measured at the time of
diagnosis in patients with chronic lymphocytic leukaemia on the time to treatment
and overal survival. METHOD: Between January 1, 2005 and December 31, 2012, 223
patients with newly-diagnosed chronic lymphocytic leukaemia were included. The
rate of patients needing treatment, time to treatment, overal survival and causes
of mortality based on Rai stages, CD38, ZAP-70 positivity and absolute monocyte
count were analyzed. RESULTS: Therapy was necessary in 21.1%, 57.4%, 88.9%, 88.9%
and 100% of patients in Rai stage 0, I, II, III an IV, respectively; in 61.9% and
60.8% of patients exhibiting CD38 and ZAP-70 positivity, respectively; and in
76.9%, 21.2% and 66.2% of patients if the absolute monocyte count was <0.25 G/l,
between 0.25-0.75 G/l and >0.75 G/l, respectively. The median time to treatment
and the median overal survival were 19.5, 65, and 35.5 months; and 41.5, 65, and
49.5 months according to the three groups of monocyte counts. The relative risk
of beginning the therapy was 1.62 (p<0.01) in patients with absolute monocyte
count <0.25 G/l or >0.75 G/l, as compared to those with 0.25-0.75 G/l, and the
risk of overal survival was 2.41 (p<0.01) in patients with absolute monocyte
count lower than 0.25 G/l as compared to those with higher than 0.25 G/l. The
relative risks remained significant in Rai 0 patients, too. The leading causes of
mortality were infections (41.7%) and the chronic lymphocytic leukaemia (58.3%)
in patients with low monocyte count, while tumours (25.9-35.3%) and other events
(48.1 and 11.8%) occurred in patients with medium or high monocyte counts.
CONCLUSIONS: Patients with low and high monocyte counts had a shorter time to
treatment compared to patients who belonged to the intermediate monocyte count
group. The low absolute monocyte count was associated with increased mortality
caused by infectious complications and chronic lymphocytic leukaemia. The
absolute monocyte count may give additional prognostic information in Rai stage
0, too.
PMID- 25845319
TI - [Reckoning: Assessment of 21 years' work in spinal surgery].
AB - INTRODUCTION: Of the world-wide used Cotrel-Dubousset instrumentation and
surgical technique providing breakthrough for the three-dimensional correction
and multi-segmental fixation of spinal deformity surgery in Hungary is linked to
the author's name, who carried out 1655 spine deformity surgeries in the last 21
years. AIM: The aim of the author was to discuss his own results in the field of
spine surgery and compare his own data to those published in the international
literature. METHOD: At the beginning hooks, followed by hybrid instrumentation
with hooks in thoracic area and transpedicular screws in lumbar spine have been
used for the segmental fixation. During the correction process, initially the
classic derotation maneuver was used, followed by the translation and then the in
situ bending techniques and, finally, a combination of the above three techniques
have been applied. RESULTS: In addition to the restoration of normal sagittal
balance, an average of 40.8 degrees (SD, 25.9), a 65.5% correction was achieved
in the frontal plane, which partly exceeds and partly consistent with the
published international results. The incidence of inflammation (3.9%), and
mechanical complications (1.7%) was similar to the international average, while
the incidence of neurological complications (0.48%) was slightly lower than the
average of international data. CONCLUSIONS: The author believes that the better
correction results as compared to the international average could be due to the
always consistent application of the Cotrel-Dubousset instrumentation correction
philosophy based on the meticulous segmental analysis of spine deformities.
PMID- 25845320
TI - [Role of implantable loop recorder in the clinical diagnosis of syncope: results
of the introduction of an effective diagnostic tool].
AB - INTRODUCTION: Extension of electrocardiographic monitoring via loop recorder
implantation may increase the diagnostic yield of syncope work-up. AIM: In this
retrospective observational study, the authors wanted to evaluate the diagnostic
performance of implantable loop recorder in the everyday clinical practice.
METHOD: The authors analyzed the electronically stored data of all patients who
underwent loop recorder implantation between 2005 and 2014 in their cardiology
department because of recurrent syncope of undetermined origin. RESULTS: There
were 52 loop recorder implantations within the study period. During the 167 (+/-
136) days of monitoring, 36 (69.2%) diagnostic events occurred. In two-thirds of
events, (46.2% of all monitored patients) a specific arrhythmia diagnosis was
reached, allowing definitive treatment in these cases. In this selected
population, there was no correlation between age, presence of known high-risk
predictors, or accompanying trauma, and the mechanism of syncope. CONCLUSIONS:
The high diagnostic rate of implantable loop recorder in the everyday clinical
practice is in accordance with the findings in prospective clinical studies. This
observation supports the early application of loop recorder in the diagnostic
algorithm of syncope.
PMID- 25845321
TI - [Symptomatology and treatment of persistent genital arousal disorder. Case
report].
AB - Persistent genital arousal disorder is a rare condition among women characterized
by unwanted and intrusive sexual arousal that can persist for an extended period
of time and unrelated to sexual desire or sexual stimuli. Since its first
documentation in 2001, numerous studies have been dedicated to investigate its
specifics. The persistent genital arousal occurs in the absence of sexual
interest and fantasies and it causes excessive psychological suffering.
Masturbation, spontaneous orgasm or sexual intercourse can offer only a temporary
relief. Researches provide a limited insight into the characteristics of
persistent genital arousal disorder. This paper presents a case and summarizes
the scientific findings on prevalence, etiology and treatment perspectives.
PMID- 25845323
TI - Aging population in Asia: Are we preparing ourselves enough?
PMID- 25845324
TI - Risk factors of suicidal ideation among adolescents after Wenchuan earthquake in
China.
AB - BACKGROUND: Suicidal ideation is a common phenomenon in survivors after disaster
event. AIM: To identify the change of suicidal ideation, and to test hypotheses
concerning the suicidal ideation, depression and PTSD symptoms among adolescent
survivors after the 2008 Wenchuan earthquake in China. METHODS: The suicidal
ideation among high school students at 6, 12 and 18 months after the Wenchuan
earthquake were investigated. Subjects included 737 student survivors in an
affected high school. The PTSD Checklist-Civilian Version (PCL-C) and the Chinese
Beck Depression Inventory (C-BDI) were used to measure the symptoms of PTSD and
depression. RESULTS: The rates of suicidal ideation among the adolescent
survivors at 6-, 12- and 18-month after the earthquake were 35.6%, 35.6% and
30.7% respectively. Depression symptoms in the 18-month follow-up, suicidal
ideations at 6 and 12 months after the earthquake were the independent risk
factors of suicidal ideation in the 18-month follow-up. Depression symptoms were
the strongest predictor of suicidal ideation after earthquake. CONCLUSION: An
increased rate of suicidal ideation after the earthquake may be mainly due to
depression but not to PTSD symptoms. The disaster-related psychological sequelae
and the risk factors of suicidal ideation, especially depression symptoms, should
be considered in the mental health services and suicide prevention.
PMID- 25845325
TI - Psychiatry and the great wall of China.
PMID- 25845326
TI - Quercetin-3-O-(2"-galloyl)-alpha-L-rhamnopyranoside attenuates cholesterol
oxidation product-induced apoptosis by suppressing NF-kappaB-mediated cell death
process in differentiated PC12 cells.
AB - Cholesterol oxidation products are suggested to be involved in neuronal cell
degeneration. We examined the preventive effect of quercetin-3-O-(2"-galloyl)
alpha-L-rhamnopyranoside (QGR), a quercetin derivative, on the cholesterol
oxidation product-induced neuronal cell death using differentiated PC12 cells in
relation to nuclear factor (NF)-kappaB-mediated apoptotic process. 7
Ketocholesterol and 25-hydroxycholesterol induced a decrease in the levels of BH3
interacting-domain death agonist (Bid) and B cell lymphoma 2 (Bcl-2), increase in
the levels of Bcl-2-associated X protein (Bax) and p53, loss of the mitochondrial
transmembrane potential, cytochrome c release, activation of caspases, and
cleavage of poly(ADP-ribose) polymerase 1 (PARP-1). 7-Ketocholesterol induced
increase in cytosolic and nuclear NF-kappaB p65, nuclear phospho-NF-kappaB p65,
cytosolic NF-kappaB p50, and cytosolic phospho-IkappaB-alpha levels. The addition
of QGR, N-acetyl cysteine, or Bay 11-7085 attenuated the cholesterol oxidation
product-induced changes in the apoptosis-related protein levels, activation of NF
kappaB, formation of reactive oxygen species, depletion of glutathione (GSH),
nuclear damage, and cell death. The results show that QGR may attenuate the
cholesterol oxidation product-induced apoptosis in PC12 cells by suppressing the
activation of the mitochondrial pathway and the caspase-8- and Bid-dependent
pathways that is mediated by NF-kappaB activation. The preventive effect appears
to be associated with the inhibitory effect on the formation of reactive oxygen
species and depletion of GSH.
PMID- 25845327
TI - Assessment of modulated cytostatic drug resistance by automated gammaH2AX
analysis.
AB - The efficacy of many chemotherapeutic agents relies on the preferential
destruction of rapidly dividing cancer cells by inducing various kinds of DNA
damage. The most deleterious type of DNA lesions are DNA double-strand breaks
(DSB), which can be detected by immunofluorescence staining of phosphorylated
histone protein H2AX (gammaH2AX). Furthermore, gammaH2AX has been suggested as
clinical pharmacodynamic biomarker in chemotherapeutic cancer treatment. A great
challenge in treating neoplastic diseases is the varying response behavior among
cancer patients. Thus, intrinsic or drug-induced overexpression of efflux pumps
often leads to multiple drug resistance (MDR) and treatment failure. In
particular, inter-individual differences in expression levels of efflux pumps,
such as the permeability glycoprotein (P-gp), were shown to correlate with cancer
progression. Several efficient cytostatic drugs, including the DSB-inducing agent
etoposide (ETP) are known P-gp substrates. In this respect, modulation of MDR by
P-gp inhibitors, like the immunosuppressives cyclosporine A (CsA) and rapamycin
(Rapa) have been described. Here, we investigated the application of gammaH2AX
focus assay to monitor the impact of CsA and Rapa on ETP-induced cytotoxicity in
human peripheral blood mononuclear cells. Evaluation of gammaH2AX foci was
performed by the automated fluorescence microscopy and interpretation system
AKLIDES. Compared to ETP treatment alone, our results revealed a significant rise
in gammaH2AX focus number and percentage of DSB-positive cells after cells have
been treated with ETP in the presence of either CsA or Rapa. In contrast, DSB
levels of cells incubated with CsA or Rapa alone were comparable to focus number
of untreated cells. Our results successfully demonstrated how automated gammaH2AX
analysis can be used as fast and reliable approach to monitor drug resistance and
the impact of MDR modulators during treatment with DSB-inducing cytostatics..
PMID- 25845328
TI - Site-specific immunochemical methylation assessment from genome DNA utilizing a
conformational difference between looped-out target and stacked-in nontarget
methylcytosines.
AB - We report the sequence-selective immunochemical discrimination of methylcytosine
from genomic DNA that we achieved by utilizing selective antibody binding to a
looped-out methylcytosine in a bulge region and without using bisulfite
treatment, a methylation-sensitive restriction enzyme, or PCR. First, we
investigated the affinity of an anti-methylcytosine antibody for methylcytosine
in full match, bulge, mismatch and abasic sites using surface plasmon resonance
measurement and a microtiter plate to explore the differences as regards antibody
binding to the target methylcytosine. The highest affinity, which was comparable
to that in a single strand of DNA, was observed in the bulge region. In
particular, no affinity was observed in a full match site. This is because there
is no interaction such as hydrogen bond or pi-pi stacking for the bulged
methylcytosine, thus enabling only the target in the bulge to be looped out.
Methylated and unmethylated genomic DNA were blended to form a model DNA with
which to assess the methylation ratio at a specific site. Fragmented DNA was
hybridized with a biotinylated probe DNA, which has a sequence capable of forming
a single base bulge at the target. The probe design is simple because it consists
solely of the elimination of guanine paired with the target cytosine from a full
match sequence. As a result, we successfully obtained a linear relationship
(r(2)=0.9962) between the immunoassay signal and the methylation ratio of a
specific site within 4 h.
PMID- 25845329
TI - Up-conversion fluorescence "off-on" switch based on heterogeneous core-satellite
assembly for thrombin detection.
AB - NaGdF4: Yb, Er nanoparticles, with up-conversion (UC) fluorescence, were used for
the first time to build an "off-on" switch based on Au core-UC satellites for
thrombin detection. We fabricated the fluorescence sensor using thrombin aptamer
modified Au core and complementary sequence modified UC satellites in liquid
phase. With optimized assembled conditions, the yield of Au core-UC satellites
achieved 80%. The fluorescence of UC nanoparticles quenched when satellite NP
attached to Au core NP. Thrombin aptamer on the surface of Au core would bind to
targets when thrombin existed in the system, then UC satellites were released and
the quenched fluorescence recovered. The sensor showed high specificity for
thrombin compared with other biomolecules and the limit of detection reached 3.5
fg/mL. Application of this sensor to detect targets in human serum also achieved
satisfactory results. The purpose of this work was to build an ultrasensitive
sensor based on Au core-UC satellites for thrombin detection in human serum to
achieve diagnosis of diseases.
PMID- 25845330
TI - Ultrasensitive electrochemical immunosensor based on orderly oriented conductive
wires for the detection of human monocyte chemotactic protein-1 in serum.
AB - For the first time, a simple, ultrasensitive and label-free electrochemical
monocyte chemotactic protein-1 (MCP-1) immunosensor based on orderly oriented
conductive wires has been developed. A conductive wire, which is similar to an
electron-conducting tunnel, was designed with Au nanoparticles (AuNPs) joined to
Au@Pt core-shell microspheres via a cysteamine (CA) crosslinker. To enhance the
sensitivity of the immunosensor, Au nanoparticles were electrodeposited onto the
gold electrode, and CA was self-assembled via strong Au-S covalent bonds,
providing an appropriate surface and promoting electron transfer. Next, Au@Pt
core-shell microspheres with large surface area were grafted onto the modified
electrode to immobilize more MCP-1 antibodies. MCP-1 is an initiating factor and
biomarker of atherosclerotic diseases. Under optimal experimental conditions,
differential pulse voltammetry (DPV) current changes were used to detect MCP-1
with a broad linear range of 0.09-360 pg mL(-1) and a low detection limit of 0.03
pg mL(-1) (S/N=3). The proposed immunosensor exhibited good selectivity,
reproducibility and reusability. When applied to spiked serum samples, the data
for the developed immunosensor were in agreement with an enzyme linked
immunosorbent assay, suggesting that the electrochemical immunosensor would be
suitable for practical detection.
PMID- 25845331
TI - Label-free electrochemical aptasensor for femtomolar detection of 17beta
estradiol.
AB - We report an electrochemical aptasensor for the rapid, label-free detection of
17beta-estradiol (E2) from femtomolar to micromolar levels. The sensor features
an aptamer-functionalised nanoporous conducting polymer electrode whose surface
potential is probed via electrochemical impedance spectroscopy. The unprecedented
detection limit for E2 is explained via the redistribution of negative charges in
the electrode double-layer region when the aptamer adopts a folded conformation
around the small neutral target molecule. The sensor responds approximately
logarithmically over a wide dynamic range of E2 concentration that spans
biological trigger levels, with excellent discrimination against structurally
similar molecules including progesterone, and robust operation in human urine.
The generality of the approach of using conformationally gated small molecule
binding aptamers is highlighted with a further example of adenosine detection via
the adenosine binding aptamer.
PMID- 25845332
TI - Enzyme-guided plasmonic biosensor based on dual-functional nanohybrid for
sensitive detection of thrombin.
AB - Rapid and sensitive methodologies for the detection of protein are in urgent
requirement for clinic diagnostics. Localized surface plasmon resonance (LSPR) of
metal nanostructures has the potential to circumvent this problem due to its
sensitive optical properties and strong electromagnetic near-field enhancements.
In this work, an enzyme mediated plasmonic biosensor on the basis of a dual
functional nanohybrid was developed for the detection of thrombin. By utilizing
LSPR-responsive nanohybrid and anaptamer-enzyme conjugated reporting probe, the
sensing platform brings enhanced signal, stability as well as simplicity.
Enzymatic reaction catalyzed the reduction of Au(3+) to Au degrees in situ,
further leading to the rapid crystal growth of gold nanoparticles (AuNPs). The
LSPR absorbance band and color changed company with the nanoparticle generation,
which can be real-time monitoring by UV-visible spectrophotometer and naked eye.
Nanohybrid constructed by gold and magnetic nanoparticles acts as a dual
functional plasmonic unit, which not only plays the role of signal production,
but also endows the sensor with the function of magnetic separation.
Simultaneously, the introduction of enzyme effectively regulates the programming
crystal growth of AuNPs. In addition, enzyme also serves as signal amplifier
owing to its high catalysis efficiency. The response of the plasmonic sensor
varies linearly with the logarithmic thrombin concentration up to 10nM with a
limit of detection of 200 pM. The as-proposed strategy shows good analytical
performance for thrombin determination. This simple, disposable method is
promising in developing universal platforms for protein monitoring, drug
discovery and point-of-care diagnostics.
PMID- 25845333
TI - Development of glucose biosensors based on nanostructured graphene-conducting
polyaniline composite.
AB - A biosensor was fabricated by immobilizing glucose oxidase (GOD) into
nanostructured graphene (GRA)-conducting polyaniline (PANI) nanocomposite, which
was based on electrochemical polymerization of aniline in GRA synthesized by
using electrochemical expansion of graphite in propylene carbonate electrolyte.
Scanning electron spectroscopy (SEM), cyclic voltammetry (CV) and electrochemical
impedance spectroscopy (EIS) were used to characterize the morphology and
performance of the as-prepared biosensor, respectively. Amperometric measurements
were carried out to optimize test conditions (pH and applied potential) of the
biosensor. Under the optimal conditions, the biosensor showed a linear range from
10.0 MUM to 1.48 mM (R(2)=0.9988) with a sensitivity of 22.1 MUA mM(-1) cm(-2),
and a detection limit of 2.769 MUM (S/N=3). The apparent Michaelis-Menten
constant (KM(a)) was estimated to be 3.26 mM. The interference from glycine
(Gly), D-galactose (D-Gal), urea (Urea), L-phenylalanine (L-Phe), ascorbic acid
(AA), and L-tyrosine (L-Tyr) was also investigated. The results indicated that
the biosensor exhibit high sensitivity and superior selectivity, providing a
hopeful candidate for glucose biosensing.
PMID- 25845334
TI - Ultrasensitive detection of drug resistant cancer cells in biological matrixes
using an amperometric nanobiosensor.
AB - Multidrug resistance (MDR) is a key issue in the failure of cancer chemotherapy
and its detection will be helpful to develop suitable therapeutic strategies for
cancer patients and overcome the death rates. In this direction, we designed a
new amperometric sensor (a medical device prototype) to detect drug resistant
cancer cells by sensing "Permeability glycoprotein (P-gp)". The sensor probe is
fabricated by immobilizing monoclonal P-gp antibody on the gold nanoparticles
(AuNPs) conducting polymer composite. The detection relies on a sandwich-type
approach using a bioconjugate, where the aminophenyl boronic acid (APBA) served
as a recognition molecule which binds with the cell surface glycans and hydrazine
(Hyd) served as an electrocatalyst for the reduction of H2O2 which are attached
on multi-wall carbon nanotube (MWCNT) (APBA-MWCNT-Hyd). A linear range for the
cancer cell detection is obtained between 50 and 100,000 cells/mL with the
detection limit of 23+/-2 cells/mL. The proposed immunosensor is successfully
applied to detect MDR cancer cells (MDRCC) in serum and mixed cell samples.
Interferences by drug sensitive (SKBr-3 and HeLa), noncancerous cells (HEK-293
and OSE), and other chemical molecules present in the real sample matrix are
examined. The sensitivity of the proposed immunosensor is excellent compared with
the conventional reporter antibody based assay.
PMID- 25845335
TI - Microfluidics and nanoparticles based amperometric biosensor for the detection of
cyanobacteria (Planktothrix agardhii NIVA-CYA 116) DNA.
AB - Some of the cyanobacteria produce protease inhibitor oligopeptides such as
cyanopeptolins and cause drinking water contamination; hence, their detection has
great importance to monitor the well-being of water sources that is used for
human consumption. In the current study, a fast and sensitive nucleic acid
biosensor assay has been described where cyanopeptolin coding region of one of
the cyanobacteria (Planktothrix agardhii NIVA-CYA 116) genome has been used as
target for monitoring of the fresh water resources. A biochip that has two sets
of Au electrode arrays, each consist of shared reference/counter electrodes and 3
working electrodes has been used for the assay. The biochip has been integrated
to a microfluidics system and all steps of the assay have been performed during
the reagent flow to achieve fast and sensitive DNA detection. On-line
hybridization of the target on to the capture probe immobilized surface resulted
in a very short assay duration with respect to the conventional static assays.
The binding of the avidin and enzyme modified Au nanoparticles to the
biotinylated detection probe and the subsequent injection of the substrate
enabled a real-time amperometric measurement with a detection limit of 6*10(-12)
M target DNA (calibration curve r(2)=0.98). The developed assay enables fast and
sensitive detection of cyanopeptolin producing cyanobacteria from freshwater
samples and hence shows a promising technology for toxic microorganism detection
from environmental samples.
PMID- 25845336
TI - Detection of methicillin-resistant staphylococci by biosensor assay consisting of
nanoscale films on optical fiber long-period gratings.
AB - Methicillin-resistance among Staphylococcus species is a major health problem in
hospitals, communities, and animals. There is a need for culture-free diagnostic
assays that can be carried out rapidly, and maintain a high degree of sensitivity
and specificity. To address this need an ionic self-assembled multilayer (ISAM)
film was deposited on the surface of a long-period grating (LPG) optical fiber by
immersion alternately in poly-allylamine hydrochloride and in poly-1-[p-(3'
carboxy-4'-hydroxyphenylazo) benzenesulfonamido]-1,2-ethandiyl (PCBS), resulting
in terminal carboxyl groups on the LPG-ISAM. The terminal carboxyl groups were
covalently conjugated to monoclonal antibodies (MAb) specific to penicillin
binding-protein 2a of methicillin resistant (MR) staphylococci. After exposure of
the LPG-ISAM to 10(2) colony forming units (CFU)/ml of MR S. aureus (MRSA) for 50
min., light transmission was reduced by 19.7%. In contrast, after exposure to
10(6) CFU/ml of methicillin-sensitive S. aureus (MSSA) attenuation of light
transmission was less than 1.8%. Exposure of the LPG-ISAM to extracts of liver,
lungs, or spleen from mice infected with MRSA attenuated light transmission by
11.7-73.5%. In contrast, exposure of the biosensor to extracts from MSSA-infected
mice resulted in 5.6% or less attenuation of light transmission. When the sensor
was tested with 36 strains of MR staphylococci, 15 strains of methicillin
sensitive staphylococci, 10 strains of heterologous genera (all at 10(4) CFU/ml),
or tissue samples from mice infected with MRSA, there was complete agreement
between MR and non-MR bacteria determined by antibiotic susceptibility testing
and the biosensor assay when the cutoff value for attenuation of light
transmission was 6.3%. Thus, the biosensor described has the potential to detect
MR staphylococci in clinical samples with a high degree of sensitivity and
specificity.
PMID- 25845337
TI - Polypyrrole encapsulation on flower-like porous NiO for advanced high-performance
supercapacitors.
AB - Polypyrrole (PPy) encapsulated 3D flower-like NiO was prepared to investigate the
role of PPy coating for high-performance electrodes. NiO@PPy showed a better
electrochemical performance than pure NiO, and a "trade-off effect" between
electrical conductivity and ion diffusion resistance was observed with different
PPy coating thickness.
PMID- 25845338
TI - Per- and polyfluoroalkyl substances in materials, humans and the environment.
PMID- 25845340
TI - Simultaneous silencing of beta-catenin and signal transducer and activator of
transcription 3 synergistically induces apoptosis and inhibits cell proliferation
in HepG2 liver cancer cells.
AB - The tumorigenesis and maintenance of a cancer cells is dependent upon the
collaboration of multiple signaling pathways. Signal transducer and activator of
transcription 3 (STAT3) and beta-catenin are at the center of multiple cancer
associated signaling pathways; therefore, simultaneously targeting STAT3 and beta
catenin may be a potential cancer treatment, leading to induced lethality of
cancer cells. In the present study, HepG2 liver cancer cells were transfected
with small interfering RNA (siRNA) against beta-catenin and STAT3 alone or in
combination. The cell growth was assessed using an MTT assay and the levels of
cell apoptosis were detected using flow cytometry. Protein levels of caspase-3,
cleaved caspase-3, poly(ADP-ribose) polymerase (PARP) and cleaved PARP were
determined using western blot analysis. Following siRNA transfection, beta
catenin and STAT3 protein levels decreased at 72 h. HepG2 cell growth inhibition
and early apoptosis in the beta-catenin and STAT3 siRNA co-transfection group
were significantly greater than those in the groups transfected with beta-catenin
or STAT3 siRNA alone. Decreased caspase-3 and PARP levels, as well as enhanced
cleavage of caspase-3 and PARP were observed in the beta-catenin and STAT3 co
transfection group. Simultaneous silencing of beta-catenin and STAT3 using siRNAs
resulted in an enhanced loss of cell viability and induction of apoptosis in
HepG2 liver cancer cells, suggesting that these genes are promising targets for
the further preclinical and clinical development of anti-cancer therapeutic
strategies, which target several cancer signaling pathways simultaneously.
PMID- 25845341
TI - Organocatalytic asymmetric addition of naphthols and electron-rich phenols to
isatin-derived ketimines: highly enantioselective construction of
tetrasubstituted stereocenters.
AB - A quinine-derived thiourea organocatalyst promoted the highly enantioselective
addition of naphthols and activated phenols to ketimines derived from isatins.
The reaction afforded chiral 3-amino-2-oxindoles with a quaternary stereocenter
in high yields (up to 99%) with excellent enantioselectivity (up to 99% ee). To
the best of our knowledge, this transformation is the first highly
enantioselective addition of naphthols to ketimines.
PMID- 25845339
TI - Impact of dietary components on NK and Treg cell function for cancer prevention.
AB - An important characteristic of cancer is that the disease can overcome the
surveillance of the immune system. A possible explanation for this resistance
arises from the ability of tumor cells to block the tumoricidal activity of host
immune cells such as natural killer (NK) cells by inducing the localized
accumulation of regulatory T (Treg) cells. Evidence exists that components in
commonly consumed foods including vitamins A, D, and E, water-soluble
constituents of mushrooms, polyphenolics in fruits and vegetables, and n-3 fatty
acids in fish oil can modulate NK cell activities, Treg cell properties, and the
interactions between those two cell types. Thus, it is extremely important for
cancer prevention to understand the involvement of dietary components with the
early stage dynamics of interactions among these immune cells. This review
addresses the potential significance of diet in supporting the function of NK
cells, Treg cells, and the balance between those two cell types, which ultimately
results in decreased cancer risk.
PMID- 25845342
TI - Changes in the Temperament and Character Inventory dimensions after paroxetine
treatment in patients with major depressive disorder.
AB - Previous studies have reported changes in the dimensions of the Temperament and
Character Inventory (TCI) after patients with major depressive disorder are
treated. We aimed to investigate the changes in the TCI dimensions after
paroxetine treatment in patients with major depressive disorder. Forty-eight
patients were enrolled in this study and were treated with 10-40 mg/day of
paroxetine for 6 weeks. The TCI was completed twice, at weeks 0 and 6. We used
the Montgomery-Asberg Depression Rating Scale (MADRS) to evaluate patients. The
participants were divided into three groups (responders, non-responders, and
early responders) based on treatment response. The scores of each dimension of
the TCI were compared before and after treatment using repeated-measures two-way
analyses of variance. In the responders group (n = 24), no TCI dimension scores
changed significantly during treatment, but the interaction between sex and MADRS
score change was significantly associated with the results. In the non-responders
group (n = 15), the self-directedness score increased significantly during the
treatment period (p = 0.000), and the change in MADRS score significantly
affected the results. In the early responders group (n = 9), no TCI dimension
scores changed significantly during treatment. The results of the present study
may reveal a possible correlation between paroxetine treatment and changes in
personality traits.
PMID- 25845343
TI - Phosphate and thiophosphate biphenyl analogs as steroid sulfatase inhibitors.
AB - In the present work, we report convenient methods for the synthesis and
biological evaluation of phosphate and thiophosphate biphenyl derivatives
exhibiting steroid sulfatase (STS) activity. The described synthesis is based on
straightforward preparation of biphenyl-4-ol and 4'-hydroxy-biphenyl-4-carboxylic
acid ethyl ester modified with various phosphate or thiophosphate moieties. The
inhibitory effects of these compounds were tested on STS isolated from human
placenta and led to two compounds of interest, 5a and 5d with IC50 values of 28.0
and 22.1 uM, respectively and that had interesting new binding modes in the STS
active site.
PMID- 25845344
TI - A rare case of a punched nerve syndrome of the deep motor branch of the ulnar
nerve.
AB - INTRODUCTION: Peripheral compression neuropathy of the ulnar nerve is a frequent
condition, most likely encountered at the ulnar sulcus or the Guyon's canal. High
resolution ultrasound (HRUS) can often identify the site of injury. Primarily
idiopathic, compression neuropathy can stem from a punched nerve syndrome, in
which direct contact between an arterial branch and the nerve leads to
compression. MATERIALS AND METHODS: A 42-year-old male patient was examined by
means of HRUS using a 17-5 MHz linear transducer on a Philips iU22((r)) (Philips,
Bothell, Washington, USA). RESULTS: After reporting a punched nerve syndrome of
the deep motor branch of the ulnar nerve distal to the Guyon's canal, the patient
underwent surgery and showed electrophysiological and clinical improvement 6
months after decompression. CONCLUSION: HRUS is a viable method to demonstrate a
punched nerve syndrome. In conjunction with clinical presentation, even unlikely
sites of compression such as the deep motor branch of the ulnar nerve can be
identified.
PMID- 25845345
TI - Non-syndromic hearing loss gene identification: A brief history and glimpse into
the future.
AB - From the first identified non-syndromic hearing loss gene in 1995, to those
discovered in present day, the field of human genetics has witnessed an
unparalleled revolution that includes the completion of the Human Genome Project
in 2003 to the $1000 genome in 2014. This review highlights the classical and
cutting-edge strategies for non-syndromic hearing loss gene identification that
have been used throughout the twenty year history with a special emphasis on how
the innovative breakthroughs in next generation sequencing technology have
forever changed candidate gene approaches. The simplified approach afforded by
next generation sequencing technology provides a second chance for the many
linked loci in large and well characterized families that have been identified by
linkage analysis but have presently failed to identify a causative gene. It also
discusses some complexities that may restrict eventual candidate gene discovery
and calls for novel approaches to answer some of the questions that make this
simple Mendelian disorder so intriguing.
PMID- 25845346
TI - Orchestrating the biosynthesis of an unnatural pyrrolysine amino Acid for its
direct incorporation into proteins inside living cells.
AB - We here report the construction of an E. coli expression system able to
manufacture an unnatural amino acid by artificial biosynthesis. This can be
orchestrated with incorporation into protein by amber stop codon suppression
inside a living cell. In our case an alkyne-bearing pyrrolysine amino acid was
biosynthesized and incorporated site-specifically allowing orthogonal double
protein labeling.
PMID- 25845347
TI - OSM is overexpressed in knee osteoarthritis and Notch signaling is involved in
the effects of OSM on MC3T3-E1 cell proliferation and differentiation.
AB - Knee osteoarthritis (OA) is the most prevalent type of OA and the cytokine,
oncostatin M (OSM), may contribute to the pathogenesis of OA. However, the exact
role of OSM in the development of knee OA and the underlying mechanisms are not
yet fully understood. This study was designed to detect the expression of OSM in
the synovial tissue of patients with knee OA. Furthermore, we investigated
whether Notch signaling is involved in the effects of OSM on MC3T3-E1 cell
proliferation and differentiation. The synovial tissue of the knee joint was
collected from 32 patients with knee OA. We detected OSM mRNA and protein
expression (by RT-qPCR and western blot analysis, respectively) in the synovial
tissue of the knee joint, and the expression level of OSM was higher in the
patients with knee OA compared with the controls. MTT assay was used in the in
vitro experiments to determine MC3T3-E1 cell proliferation, and cell
differentiation was determined by measuring alkaline phosphatase (ALP) activity
and osteocalcin (OCN) expression. The results from our in vitro experiments
revealed that OSM induced bone formation by increasing osteoblast cell
proliferation and differentiation. In addition, the expression levels of Notch
ligand, receptor and target gene, including Delta-like 1 (Dll1), Notch homolog 1
(Notch1) and Hes family bHLH transcription factor 1 (Hes1) were decreased
following treatment with OSM in a time-dependent manner in the MC3T3-E1 cells. A
Dll1 overexpression vector was transfected into the cells to activate Notch
signaling, and the results revealed that the activation of Notch signaling
attenuated the effects of OSM on MC3T3-E1 cell proliferation and differentiation.
In conclusion, our data demonstrate that elevated levels of OSM in synovial
tissue induce bone formation by increasing osteoblast cell proliferation and
differentiation. The Notch signaling pathway was found to be one of the signaling
pathways that inhibit OSM-induced MC3T3-E1 cell proliferation and
differentiation. The findings of this study may broaden our understanding of the
mechanisms behing the role of OSM in the development of knee OA.
PMID- 25845351
TI - Plasma lipid analysis by hydrophilic interaction liquid chromatography coupled
with electrospray ionization tandem mass spectrometry.
AB - A novel method for the analysis of endogenous lipids and related compounds was
developed employing hydrophilic interaction liquid chromatography with
electrospray ionization tandem mass spectrometry. A hydrophilic interaction
liquid chromatography with carbamoyl stationary phase achieved clear separation
of phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, ceramide, and
mono-hexsosyl ceramide groups with good peak area repeatability (RSD% < 10) and
linearity (R(2) > 0.99). The established method was applied to human plasma
assays and a total of 117 endogenous lipids were successfully detected and
reproducibly identified. In addition, we investigated the simultaneous detection
of small polar metabolites such as amino and organic acids co-existing in the
same biological samples processed in a single analytical run with lipids. Our
results show that hydrophilic interaction liquid chromatography is a useful tool
for human plasma lipidome analysis and offers more comprehensive metabolome
coverage.
PMID- 25845352
TI - Do proton pump inhibitors contribute to weight gain?
PMID- 25845354
TI - Trail following response of larval Cactoblastis cactorum to 2-acyl-1,3
cyclohexanediones.
AB - Caterpillars of Cactoblastis cactorum secrete onto the surface of host cactuses
droplets of an oily fluid that issues from the orifices of their paired
mandibular glands. The fluid contains a series of 2-acyl-1,3-cyclohexanediones
that, collectively, have been shown to elicit trail-following behavior from the
caterpillars. This study reports the results of bioassays to determine the
ability of two specific compounds, previously shown to be prominent components of
the mandibular glands of pyralid caterpillars, 4-hydroxy-2-oleoyl-1,3
cyclohexanedione and 2-oleoyl-1,3-cyclohexanedione, to elicit trail-following
behavior from the larvae of C. cactorum. Additionally bioassayed were structural
fragments of these molecules. The relative effectiveness of the chemicals in
eliciting trail following, the effect of varying concentration on the trail
following response, the importance of specific functional groups to the trail
following response, and the threshold sensitivity of the caterpillar to the
pheromone were determined. The study showed that while all the tested compounds
elicited some degree of trail following, they differed significantly in their
effectiveness. The most effective of the compounds was 4-hydroxy-2-oleoyl-1,3
cyclohexanedione, which, on a per unit volume basis, was as effective as whole
gland extract. Caterpillars secreted large quantities of fluid from the glands,
and the threshold response to 4-hydroxy-2-oleoyl-1,3-cyclohexanedione occurred at
a relative high application rate compared to trail pheromones of other social
caterpillars and eusocial insects. This and the observation that the trail marker
is secreted from the mandibular glands suggests that the use of 2-acyl-1,3
cyclohexanediones as trail markers is secondary, and that these compounds
function primarily in some other, as yet undetermined, context.
PMID- 25845353
TI - Preoperative Predictive Factors of Successful Weight Loss and Glycaemic Control 1
Year After Gastric Bypass for Morbid Obesity.
AB - BACKGROUND: Gastric bypass (GBP) is one of the most effective surgical procedures
to treat morbid obesity and the related comorbidities. This study aimed at
identifying preoperative predictors of successful weight loss and type 2 diabetes
mellitus (T2DM) remission 1 year after GBP. METHODS: Prospective longitudinal
study of 771 patients who underwent GBP was performed at four Italian centres
between November 2011 and May 2013 with 1-year follow-up. Preoperative
anthropometric, metabolic and social parameters, the surgical technique and the
previous failed bariatric procedures were analyzed. Weight, the body mass index
(BMI), the percentage of excess weight lost (% EWL), the percentage of excess BMI
lost (% BMIL) and glycated haemoglobin (HbA1c) were recorded at follow-up.
RESULTS: Univariate and multivariate analysis showed that BMI <50 kg/m(2) (p =
0.006) and dyslipidaemia (p = 0.05) were predictive factors of successful weight
loss. Multivariate analysis of surgical technique showed significant weight loss
in patients with a small gastric pouch (p < 0.001); the lengths of alimentary and
biliary loops showed no statistical significance. All diabetic patients had a
significant reduction of HbA1c (p < 0.001) after surgery. BMI >= 50 kg/m(2) (p =
0.02) and low level of preoperative HbA1c (p < 0.01) were independent risk
factors of T2DM remission after surgery. CONCLUSIONS: This study provides a
useful tool for making more accurate predictions of best results in terms of
weight loss and metabolic improvement.
PMID- 25845355
TI - Cadmium, copper, and lead accumulation and bioconcentration in the vegetative and
reproductive organs of Raphanus sativus: implications for plant performance and
pollination.
AB - Several studies have found high levels of cadmium (Cd), copper (Cu), and lead
(Pb) in honey bee hives located near urbanized or industrial areas. Insect
herbivores and pollinators may come in contact with environmental contaminants in
the leaves and flowers they forage upon in these areas. Our study quantified
which of these metals are accumulated in the tissues of a common weedy plant that
can serve as a route of exposure for insects. We grew Raphanus sativus (crop
radish) in semi-hydroponic sand culture in the greenhouse. Plants were irrigated
with nutrient solutions containing Cd, Cu, or Pb at four concentrations (control,
low, medium, high). Plant performance, floral traits, and metal accumulation were
measured in various vegetative and reproductive plant organs. Floral traits and
flower number were unaffected by all metal treatments. Copper accumulated at the
highest concentrations in flowers compared to the other two metals. Copper and Cd
had the highest translocation indices, as well as higher bioconcentration factors
compared to Pb, which was mostly immobile in the plant. Copper posed the highest
risk due to its high mobility within the plant. In particular, accumulation of
metals in leaves and flowers suggests that herbivores and pollinators visiting
and foraging on these tissues may be exposed to these potentially toxic
compounds.
PMID- 25845356
TI - A membraneless air-breathing hydrogen biofuel cell based on direct wiring of
thermostable enzymes on carbon nanotube electrodes.
AB - A biocathode was designed by the modification of a carbon nanotube (CNT) gas
diffusion electrode with bilirubin oxidase from Bacillus pumilus, achieving high
current densities up to 3 mA cm(-2) for the reduction of O2 from air. A
membraneless air-breathing hydrogen biofuel cell was designed by combination of
this cathode with a functionalized CNT-based hydrogenase anode.
PMID- 25845357
TI - Hourly differences in air pollution on the risk of asthma exacerbation.
AB - We investigated the association between hourly differences in air pollution and
asthma exacerbation in Korea using asthma-related emergency department data and
verified seasonality and demographic modifiers with an hourly temporal
resolution. We applied time-stratified case-crossover adjusted for weather and
influenza; the lag was stratified as 1-6, 7-12, 13-18, 19-24, 25-48, and 49-72 h.
Odds ratios (95% confidence interval) per interquartile range increase were 1.05
(1.00-1.11) after 1-6 h for PM10-2.5 and 1.10 (1.04-1.16) after 19-24 h for O3.
Effect size was 1.14 (1.06-1.22) at a 1-6 h lag in spring for PM10-2.5, and 1.25
(1.03-1.51) at a 25-48 h lag in winter for O3. O3 effects were age- and low socio
economic status-modified at a 7-12 h lag [1.25 (1.04-1.51)]. Increased PM10-2.5
and O3 increased the risk of asthma exacerbation; the effect of PM10-2.5 was most
immediate.
PMID- 25845358
TI - A biodynamic model predicting waterborne lead bioaccumulation in Gammarus pulex:
Influence of water chemistry and in situ validation.
AB - Metals bioaccumulated in aquatic organisms are considered to be a good indicator
of bioavailable metal contamination levels in freshwaters. However,
bioaccumulation depends on the metal, the species, and the water chemistry that
influences metal bioavailability. In the laboratory, a kinetic model was used to
describe waterborne Pb bioaccumulated in Gammarus pulex. Uptake and elimination
rate constants were successfully determined and the effect of Ca(2+) on Pb uptake
was integrated into the model. Thereafter, accumulated Pb concentrations in
organisms were predicted with the model and compared with those measured in
native populations from the Seine watershed (France). The predictions had a good
agreement with the bioaccumulation levels observed in native gammarids and
particularly when the effect of calcium was considered. To conclude, kinetic
parameters experimentally derived for Pb in G. pulex are applicable in
environmental conditions. Moreover, the consideration of the water's chemistry is
crucial for a reliable interpretation of bioaccumulation.
PMID- 25845359
TI - Synthetic promoters consisting of defined cis-acting elements link multiple
signaling pathways to probenazole-inducible system.
AB - Probenazole (3-allyloxy-1,2-benzisothiazole-1,1-dioxide, PBZ), the active
component of Oryzemate, could induce systemic acquired resistance (SAR) in plants
through the induction of salicylic acid (SA) biosynthesis. As a widely used
chemical inducer, PBZ is a good prospect for establishing a new chemical
inducible system. We first designed artificially synthetic promoters with tandem
copies of a single type of cis-element (SARE, JERE, GCC, GST1, HSRE, and W-box)
that could mediate the expression of the beta-glucuronidase (GUS) reporter gene
in plants upon PBZ treatment. Then we combined different types of elements in
order to improve inducibility in the PBZ-inducible system. On the other hand, we
were surprised to find that the cis-elements, which are responsive to jasmonic
acid (JA) and ethylene, also responded to PBZ, implying that SA, JA, and ethylene
pathways also would play important roles in PBZ's action. Further analysis
demonstrated that PBZ also induced early events of innate immunity via a
signaling pathway in which Ca(2+) influx and mitogen-activated protein kinase
(MAPK) activity were involved. We constructed synthesized artificial promoters to
establish a PBZ chemical-inducible system, and preliminarily explored SA, JA,
ethylene, calcium, and MAPK signaling pathways via PBZ-inducible system, which
could provide an insight for in-depth study.
PMID- 25845360
TI - Alternaria toxin-induced resistance in rose plants against rose aphid
(Macrosiphum rosivorum): effect of tenuazonic acid.
AB - Many different types of toxins are produced by the fungus, Alternaria alternata
(Fr.) Keissler. Little is known, however, regarding the influence of these toxins
on insects. In this study, we investigated the toxin-induced inhibitory effects
of the toxin produced by A. alternata on the rose aphid, Macrosiphum rosivorum,
when the toxin was applied to leaves of the rose, Rosa chinensis. The results
demonstrated that the purified crude toxin was non-harmful to rose plants and
rose aphids, but had an intensive inhibitory effect on the multiplication of
aphids. The inhibitory index against rose aphids reached 87.99% when rose plants
were sprayed with the toxin solution at a low concentration. Further results from
bioassays with aphids and high performance liquid chromatography (HPLC) analyses
demonstrated that tenuazonic acid (TeA) was one of the most important resistance
related active components in the crude toxin. The content of TeA was 0.1199% in
the crude toxin under the HPLC method. Similar to the crude toxin, the inhibitory
index of pure TeA reached 83.60% 15 d after the rose plants were sprayed with
pure TeA solution at the lower concentration of 0.060 MUg/ml, while the contents
of residual TeA on the surface and in the inner portion of the rose plants were
only 0.04 and 0.00 ng/g fresh weight of TeA-treated rose twigs, respectively, 7 d
after the treatment. Our results show that TeA, an active component in the A.
alternata toxin, can induce the indirect plant-mediated responses in rose plants
to intensively enhance the plant's resistances against rose aphids, and the
results are very helpful to understand the plant-mediated interaction between
fungi and insects on their shared host plants.
PMID- 25845361
TI - Evaluation of yeasts from Tibetan fermented products as agents for biocontrol of
blue mold of Nashi pear fruits.
AB - A total of 20 strains of yeast isolated from Tibetan fermented products were
screened for antagonism against blue mold of pear caused by Penicillium expansum.
Six isolates that inhibited incidence of postharvest decay by 35% or more were
selected for further screening. Among them, the most effective was Rhodotorula
mucilaginosa. The results showed that washed cell suspensions of R. mucilaginosa
yielded better antagonistic efficacy than unwashed cell-culture mixtures, cell
free culture filtrates, and autoclaved cell cultures. Biocontrol activity
improved with increasing concentrations of incubated cells. The best
concentration was 1*10(8) cells/ml, at which the incidence of decay was only
16.7% after 6 d of incubation. The germination of conidia of P. expansum in vitro
was significantly inhibited by both washed cell-suspensions and unwashed cell
culture mixtures. Rapid colonization by yeast at different concentrations showed
a relationship between yeast-cell concentration and biocontrol activity. Although
the titratable acidity of pear fruits increased after treatment, R. mucilaginosa
did not affect the total soluble solids or ascorbic acid content. This is the
first study to report that the yeast R. mucilaginosa from Tibet Autonomous Region
of China may have potential as an antagonist to control the postharvest decay of
pear fruits.
PMID- 25845362
TI - Mutation breeding of high 4-androstene-3,17-dione-producing Mycobacterium
neoaurum ZADF-4 by atmospheric and room temperature plasma treatment.
AB - Steroid medication is used extensively in clinical applications and comprises a
large and vital part of the pharmaceutical industry. However, the difficulty of
separating 4-androstene-3,17-dione (AD) from 1,4-androstadiene-3,17-dione (ADD)
restricts the application of the microbial transformation of phytosterols in the
industry. A novel atmospheric and room temperature plasma (ARTP) treatment, which
employs helium as the working gas, was used to generate Mycobacterium neoaurum
mutants producing large amounts of AD. After treatment of cultures with ARTP,
four mutants were selected using a novel screening method with a color assay.
Among the mutants, M. neoaurum ZADF-4 was considered the best candidate for
industrial application. When the fermentation medium contained 15 g/L
phytosterols and was cultivated on a rotary shaker at 160 r/min at 30 degrees C
for 7 d, (6.28+/-0.11) g/L of AD and (0.82+/-0.05) g/L of ADD were produced by
the ZADF-4 mutant, compared with (4.83+/-0.13) g/L of AD and (2.34+/-0.06) g/L of
ADD by the original strain, M. neoaurum ZAD. Compared with ZAD, the molar yield
of AD increased from 48.3% to 60.3% in the ZADF-4 mutant. This result indicates
that ZADF-4 may have potential for industrial production of AD.
PMID- 25845363
TI - Expression profiles of miRNAs in Gossypium raimondii.
AB - miRNAs are a class of conserved, small, endogenous, and non-protein-coding RNA
molecules with 20-24 nucleotides (nt) in length that function as post
transcriptional modulators of gene expression in eukaryotic cells. Functional
studies have demonstrated that plant miRNAs are involved in the regulation of a
wide range of plant developmental processes. To date, however, no research has
been carried out to study the expression profiles of miRNAs in Gossypium
raimondii, a model cotton species. We selected 16 miRNAs to profile their tissue
specific expression patterns in G. raimondii four different tissues, and these
miRNAs are reported to play important roles in plant growth and development. Our
results showed that the expression levels of these miRNAs varied significantly
from one to another in a tissue-dependent manner. Eight miRNAs, including miR
159, miR-162, miR-164, miR-172, miR-390, miR-395, miR-397, and miR-398, exhibited
exclusively high expression levels in flower buds, suggesting that these miRNAs
may play significant roles in floral development. The expression level of miR-164
was relatively high in shoots beside flower buds, implying that the function of
miR-164 is not only limited to floral development but it may also play an
important role in shoot development. Certain miRNAs such as miR-166 and miR-160
were extremely highly expressed in all of the four tissues tested compared with
other miRNAs investigated, suggesting that they may play regulatory roles at
multiple development stages. This study will contribute to future studies on the
functional characterization of miRNAs in cotton.
PMID- 25845364
TI - Cassava stillage and its anaerobic fermentation liquid as external carbon sources
in biological nutrient removal.
AB - The aim of this study was to investigate the effects of one kind of food industry
effluent, cassava stillage and its anaerobic fermentation liquid, on biological
nutrient removal (BNR) from municipal wastewater in anaerobic-anoxic-aerobic
sequencing batch reactors (SBRs). Experiments were carried out with cassava
stillage supernatant and its anaerobic fermentation liquid, and one pure compound
(sodium acetate) served as an external carbon source. Cyclic studies indicated
that the cassava by-products not only affected the transformation of nitrogen,
phosphorus, poly-beta-hydroxyalkanoates (PHAs), and glycogen in the BNR process,
but also resulted in higher removal efficiencies for phosphorus and nitrogen
compared with sodium acetate. Furthermore, assays for phosphorus accumulating
organisms (PAOs) and denitrifying phosphorus accumulating organisms (DPAOs)
demonstrated that the proportion of DPAOs to PAOs reached 62.6% (Day 86) and
61.8% (Day 65) when using cassava stillage and its anaerobic fermentation liquid,
respectively, as the external carbon source. In addition, the nitrate utilization
rates (NURs) of the cassava by-products were in the range of 5.49-5.99 g N/(kg
MLVSS?h) (MLVSS is mixed liquor volatile suspended solids) and 6.63-6.81 g N/(kg
MLVSS?h), respectively. The improvement in BNR performance and the reduction in
the amount of cassava stillage to be treated in-situ make cassava stillage and
its anaerobic fermentation liquid attractive alternatives to sodium acetate as
external carbon sources for BNR processes.
PMID- 25845365
TI - Effect of culturing conditions on the expression of key enzymes in the
proteolytic system of Lactobacillus bulgaricus.
AB - The proteolytic system of Lactobacillus bulgaricus breaks down milk proteins into
peptides and amino acids, which are essential for the growth of the bacteria. The
aim of this study was to determine the expressions of seven key genes in the
proteolytic system under different culturing conditions (different phases,
initial pH values, temperatures, and nitrogen sources) using real-time polymerase
chain reaction (RT-PCR). The transcriptions of the seven genes were reduced by 30
fold on average in the stationary phase compared with the exponential growth
phase. The transcriptions of the seven genes were reduced by 62.5-, 15.0-, and
59.0-fold in the strains KLDS 08006, KLDS 08007, and KLDS 08012, respectively,
indicating that the expressions of the seven genes were significantly different
among strains. In addition, the expressions of the seven genes were repressed in
the MRS medium containing casein peptone. The effect of peptone supply on PepX
transcription was the weakest compared with the other six genes, and the impact
on OppD transcription was the strongest. Moreover, the expressions of the seven
genes were significantly different among different strains (P<0.05). All these
results indicated that the culturing conditions affected the expression of the
proteolytic system genes in Lactobacillus bulgaricus at the transcription level.
PMID- 25845366
TI - Transcatheter aortic valve implantation for Chinese patients with bicuspid aortic
valve.
PMID- 25845367
TI - Looking for protein stabilizing drugs with thermal shift assay.
AB - Thermal shift assay can be used for the high-throughput screening of
pharmacological chaperones. These drugs are small molecules that bind a mutant
protein and stabilize it. We demonstrated the robustness, reproducibility and
versatility of the method using two molecules that are in clinical trial for
Fabry or Pompe disease, Deoxygalactonojirimycin and N-Butyldeoxynojirimycin, and
their target enzymes, lysosomal alpha-galactosidaseA and alpha-glucosidase, as
test cases. We assessed the influence of solvents and of scanning rate on the
measures. We showed that a value that is equivalent to the melting temperature
can be obtained by the first derivatives of raw data. We discuss the advantages
of the method and the precaution to be taken in running the experiments.
PMID- 25845368
TI - Mechano-sensitive nociceptors are required to detect heat pain thresholds and
cowhage itch in human skin.
AB - BACKGROUND: Mechano-sensitive and mechano-insensitive C-nociceptors in human skin
differ in receptive field sizes and electrical excitation thresholds, but their
distinct functional roles are yet unclear. METHODS: After blocking the lateral
femoral cutaneous nerve (NCFL) in eight healthy male subjects (3-mL Naropin((r))
1%), we mapped the skin innervation territory being anaesthetic to mechanical pin
prick but sensitive to painful transcutaneous electrical stimuli. Such
'differentially anaesthetic zones' indicated that the functional innervation with
mechano-sensitive nociceptors was absent but the innervation with mechano
insensitive nociceptors remained intact. In these areas, we explored heat pain
thresholds, low pH-induced pain, cowhage- and histamine-induced itch, and axon
reflex flare. RESULTS: In differentially anaesthetic skin, heat pain thresholds
were above the cut-off of 50 degrees C (non-anaesthetized skin 47 +/- 0.4 degrees
C). Pain ratings to 30 MUL pH 4 injections were reduced compared to non
anaesthetized skin (48 +/- 9 vs. 79 +/- 6 VAS; p < 0.01). The axon reflex flare
area did not differ between these zones (7.8 +/- 1.4 cm(2) vs. 8.3 +/- 0.5 cm(2)
). Histamine iontophoresis still caused pruritus in differentially anaesthetized
skin in five of eight subjects (VAS 26 +/- 14), whereas itch upon cowhage
spicules was absent (VAS 0 vs. 29 +/- 11 in non-anaesthetized skin). CONCLUSIONS:
We conclude that activation of mechano-insensitive nociceptors is sufficient to
provoke itch by histamine- and acid-induced pain. The mechano-sensitive
nociceptors are crucial for cowhage-induced itch and for the assessment of heat
pain thresholds.
PMID- 25845369
TI - Contractile activity is required for Z-disc sarcomere maturation in vivo.
AB - Sarcomere structure underpins structural integrity, signaling, and force
transmission in the muscle. In embryos of the frog Xenopus tropicalis, muscle
contraction begins even while sarcomerogenesis is ongoing. To determine whether
contractile activity plays a role in sarcomere formation in vivo, chemical tools
were used to block acto-myosin contraction in embryos of the frog X. tropicalis,
and Z-disc assembly was characterized in the paralyzed dicky ticker mutant.
Confocal and ultrastructure analysis of paralyzed embryos showed delayed Z-disc
formation and defects in thick filament organization. These results suggest a
previously undescribed role for contractility in sarcomere maturation in vivo.
PMID- 25845370
TI - Characterization of adolescent and pediatric renal cell carcinoma: A report from
the Children's Oncology Group study AREN03B2.
AB - BACKGROUND: The current study was conducted to characterize the epidemiology,
histology, and radiographic features of as well as the surgical approach to
pediatric and adolescent renal cell carcinoma (pRCC). METHODS: pRCC cases
prospectively enrolled on the Children's Oncology Group study AREN03B2 underwent
central pathology, radiology, surgery, and oncology review. RESULTS: As of June
2012, 120 of a total of 3250 patients enrolled on AREN03B2 (3.7%) were found to
have unilateral RCC (median age, 12.9 years [range, 1.9-22.1 years]; 52.5% were
female). Central review classified these as translocation morphology (56
patients), papillary (20 patients), renal medullary carcinoma (13 patients),
chromophobe (4 patients), oncocytoma (1 patient), conventional clear cell (1
patient), and RCC not otherwise specified (25 patients). Lymph node (LN)
involvement (N+) was found in 35 of 73 cases (47.9%) for which LNs were sampled,
including 19 of 40 cases with primary tumors measuring <7 cm (47.5%). Using a
size cutoff of 1 cm, imaging detection of LN involvement had a sensitivity of
57.14% (20 of 35 cases; 95% CI, 39.35%-73.68%) and a specificity of 94.59% (35 of
37 cases; 95% CI, 81.81%-99.34%). Distant metastases were present in 23 cases
(19.2%). Initial surgery was radical nephrectomy in 88 patients (73.3%), nephron
sparing surgery in 18 patients (15.0%), and biopsy in 14 patients (11.7%).
Compared with patients undergoing radical nephrectomy, those treated with nephron
sparing surgery were less likely to have LNs sampled (6 of 18 patients [33.3%] vs
65 of 88 patients [73.9%]; P = .002). CONCLUSIONS: Translocation RCC is the most
common form of pediatric and adolescent RCC. Lymph node disease is common and
observed among patients with small primary tumors. Imaging has a high specificity
but relatively low sensitivity for the detection of such lymph node disease.
Failure to sample LNs results in incomplete staging and potentially inadequate
disease control for younger patients with RCC.
PMID- 25845372
TI - PGE2 MEDIATES OENOCYTOID CELL LYSIS VIA A SODIUM-POTASSIUM-CHLORIDE
COTRANSPORTER.
AB - Prostaglandin E2 (PGE2 ) mediates immune responses of the beet armyworm,
Spodoptera exigua, including oenocytoid cell lysis (a class of lepidopteran
hemocytes: OCL) via its specific membrane receptor to release inactive
prophenoloxidase (PPO) into hemolymph. PPO is activated into phenoloxidase in the
plasma to play crucial roles in the immune responses of S. exigua. The mechanism
of OCL has not been elucidated, however we posed the hypothesis that a rapid
accumulation of sodium ions within the oenocytoids allows a massive influx of
water by the ion gradient, which leads to the cell lysis. It remains unclear
which sodium channel is responsible for the OCL in response to PGE2 . This study
identified a specific sodium channel called sodium-potassium-chloride
cotransporter 1 (Se-NKCC1) expressed in hemocytes of S. exigua and analyzed its
function in the OCL in response to PGE2 . Se-NKCC1 encodes a basic membrane
protein (pI value = 8.445) of 1,066 amino acid residues, which contains 12
putative transmembrane domains. Se-NKCC1 was expressed in all developmental
stages and tissues. qPCR showed that bacterial challenge significantly induced
its expression. A specific inhibitor of NKCC, bumetanide, prevented the OCL in a
dose-dependent manner. When RNA interference (RNAi) using double-stranded RNA
specific to Se-NKCC1 suppressed its expression, the OCL and PPO activation were
significantly inhibited in response to PGE2 . The RNAi treatment also reduced
nodule formation to bacterial challenge. These results suggest that Se-NKCC1 is
associated with OCL by facilitating inward transport of ions in response to PGE2
.
PMID- 25845374
TI - Population Approaches for Detecting Glucose Disorders.
AB - Globally, 382 million adults aged 20-79 years are estimated to have diabetes and
46% are unaware of their condition. Another 316 million adults are at increased
risk of developing diabetes. Although there are suggestions that diabetes and
related complications can be prevented through early detection, lifestyle
intervention and/or treatment, universal screening for diabetes has not been
adopted. There are, instead, recommendations for a multi-step screening approach,
which include identifying people at risk of diabetes through non-invasive methods
such as a risk assessment tool or presence of diabetes risk factors, followed by
blood testing for the at risk group and diagnostic blood testing for those
screened positive for diabetes. Diabetes screening initiatives have been studied
in different medical, health and community settings and some have targeted high
risk populations. Most of these screening initiatives, however, have common
limitations such as low follow-up rate with primary care providers for those who
screen positive, abnormal screening result not communicated to the at risk
person's primary care provider, failure to provide appropriate follow-up for
patients with abnormal screening results, time and cost as barriers for both
screening providers and people invited for screening, and low acceptance of the
oral glucose tolerance test. If these common limitations can be addressed,
diabetes screening initiatives have the potential to detect undiagnosed diabetes
in most populations.
PMID- 25845371
TI - Familial Ehlers-Danlos syndrome with lethal arterial events caused by a mutation
in COL5A1.
AB - Different forms of Ehlers-Danlos syndrome (EDS) exist, with specific phenotypes
and associated genes. Vascular EDS, caused by heterozygous mutations in the
COL3A1 gene, is characterized by fragile vasculature with a high risk of
catastrophic vascular events at a young age. Classic EDS, caused by heterozygous
mutations in the COL5A1 or COL5A2 genes, is characterized by fragile,
hyperextensible skin and joint laxity. To date, vessel rupture in four unrelated
classic EDS patients with a confirmed COL5A1 mutation has been reported. We
describe familial occurrence of a phenotype resembling vascular EDS in a mother
and her two sons, who all died at an early age from arterial ruptures. Diagnostic
Sanger sequencing in the proband failed to detect aberrations in COL3A1, COL1A1,
COL1A2, TGFBR1, TGFBR2, SMAD3, and ACTA2. Next, the proband's DNA was analyzed
using a next-generation sequencing approach targeting 554 genes linked to
vascular disease (VASCULOME project). A novel heterozygous mutation in COL5A1 was
detected, resulting in an essential glycine substitution at the C-terminal end of
the triple helix domain (NM_000093.4:c.4610G>T; p.Gly1537Val). This mutation was
also present in DNA isolated from autopsy material of the index's brother. No
material was available from the mother, but the mutation was excluded in her
parents, siblings and in the father of her sons, suggesting that the COL5A1
mutation occurred in the mother's genome de novo. In conclusion, we report
familial occurrence of lethal arterial events caused by a COL5A1 mutation.
PMID- 25845375
TI - The ultrasound-guided fat transplantation.
PMID- 25845376
TI - Personalized Strategies to Activate and Empower Patients in Health Care and
Reduce Health Disparities.
AB - Designing culturally sensitive personalized interventions is essential to sustain
patients' involvement in their treatment and encourage patients to take an active
role in their own health and health care. We consider patient activation and
empowerment as a cyclical process defined through patient accumulation of
knowledge, confidence, and self-determination for their own health and health
care. We propose a patient-centered, multilevel activation and empowerment
framework (individual-, health care professional-, community-, and health care
delivery system-level) to inform the development of culturally informed
personalized patient activation and empowerment (P-PAE) interventions to improve
population health and reduce racial and ethnic disparities. We discuss relevant
Affordable Care Act payment and delivery policy reforms and how they affect
patient activation and empowerment. Such policies include Accountable Care
Organizations and value-based purchasing, patient-centered medical homes, and the
community health benefit. Challenges and possible solutions to implementing the P
PAE are discussed. Comprehensive and longitudinal data sets with consistent P-PAE
measures are needed to conduct comparative effectiveness analyses to evaluate the
optimal P-PAE model. We believe the P-PAE model is timely and sustainable and
will be critical to engaging patients in their treatment, developing patients'
abilities to manage their health, helping patients express concerns and
preferences regarding treatment, empowering patients to ask questions about
treatment options, and building up strategic patient-provider partnerships
through shared decision making.
PMID- 25845377
TI - A brief journey through the immune system.
AB - This review serves as an introduction to an Immunology Series for the
Nephrologist published in CJASN. It provides a brief overview of the immune
system, how it works, and why it matters to kidneys. This review describes in
broad terms the main divisions of the immune system (innate and adaptive), their
cellular and tissue components, and the ways by which they function and are
regulated. The story is told through the prism of evolution in order to relay to
the reader why the immune system does what it does and why imperfections in the
system can lead to renal disease. Detailed descriptions of cell types, molecules,
and other immunologic curiosities are avoided as much as possible in an effort to
not detract from the importance of the broader concepts that define the immune
system and its relationship to the kidney.
PMID- 25845378
TI - Biological activation of zirconia surfaces by chemical modification with IGF-1.
AB - The purpose of this study was to improve the adhesion and extension of human
gingival epithelial cells (HGECs) to the yttria-stabilized zirconia polycrystal
(Y-TZP) surfaces by immobilization of insulin-like growth factor 1 (IGF-1).
Surface analyses by Fourier transform infrared spectroscopy (FTIR) and X-ray
photoelectron spectroscopy (XPS) showed that IGF-1 was successfully immobilized
on the Y-TZP surfaces. There was no significant difference between the number of
cells attached to the IGF-1-immobilized Y-TZP surfaces and on the as-polished Y
TZP surfaces either at 3 or 72 h. However, IGF-1-immobilized Y-TZP surfaces
yielded a significantly higher expression of integrin beta4 mRNA and laminin-5
mRNA, and enhanced adhesion strength of HGECs after 72 h of incubation. There was
no difference between the amount of adhered Streptococcus gordonii (S. gordonii)
found on the IGF-1-immobilized Y-TZP surfaces and on the as-polished Y-TZP
surfaces. These results suggested that the IGF-1-immobilized Y-TZP surfaces
developed using the method reported herein enhanced the adhesion and extension of
HGECs to the Y-TZP surfaces without enhancing S. gordonii adhesion.
PMID- 25845379
TI - Tribbles homolog 3 is induced by high glucose and associated with apoptosis in
human endothelial cells.
AB - Tribbles homolog 3 (TRIB3) is an intracellular kinase-like molecule that modifies
cellular survival and metabolism. The present study aimed to investigate the
function of TRIB3 regulation in the process of high glucose-induced apoptosis in
endothelial cells, with the aim of identifying a novel intervention target for
the prevention and treatment of diabetes mellitus. Human umbilical vein
endothelial cells (HUVECs) grown in medium with various concentrations of glucose
(5.5, 10, 20, 30 and 40 mmol/l) were assessed for mRNA expression of TRIB1, TRIB2
and TRIB3 using reverse transcription quantitative polymerase chain reaction. In
addition, protein expression of TRIB3 was examined using western blot analysis.
Immunofluorescence staining was performed in order to determine the distribution
and localization of TRIB3 in HUVECs. Furthermore, cells grown in normal (5.5
mmol/l) or high glucose (HG; 30 mmol/l) medium were subjected to TRIB3 inhibition
through small interfering (si)RNA knockdown. These cells were then examined in
order to determine whether TRIB3 upregulation was associated with endothelial
cell apoptosis. HUVECs treated with 30 and 40 mmol/l glucose for 48 h and 72 h
showed significantly lower survival rates compared with those treated with normal
glucose levels. In addition, slight but not significant increases in TRIB1 and
TRIB2 mRNA expression were observed in HUVECs incubated with various
concentrations of glucose for different durations. By contrast, TRIB3 mRNA
expression was increased 7.2-fold following incubation with HG. Western blot
analysis revealed a 5.44-fold increase in TRIB3 protein levels in cells grown in
HG medium for 24 h compared with those grown in normal medium. Immunostaining
assays revealed a markedly higher and well-defined nucleolar fluorescence
intensity for TRIB3 expression at 24 h in HG medium compared with that of the
control group. Furthermore, the apoptotic rate of HG-treated TRIB3 siRNA
transfected HUVECs was significantly increased compared with that of those
transfected with control siRNA In conclusion, the results of the present study
suggested that TRIB3 was associated with high glucose-induced HUVECs apoptosis,
which was attenuated following transfection with TRIB3 siRNA.
PMID- 25845380
TI - Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects,
mechanisms and clinical application potential (Review).
AB - The morbidity and mortality of prostate cancer have been increasing recently, and
the comprehensive treatment for prostate cancer is unable to achieve satisfactory
outcomes. Quercetin is a natural flavonoid compound that has attracted increased
interest and attention due to its anticancer activity. In vitro and in vivo
studies have verified that quercetin effectively inhibits prostate cancer via
various mechanisms. Clinical trails concerning the pharmacokinetics and
application of quercetin in humans have also obtained promising results.
Meanwhile, epidemiologic studies have demonstrated a negative association between
quercetin intake and prostate cancer incidence and have suggested a
chemopreventive effect of quercetin on prostate cancer that has been exhibited in
animal experiments. The main issue concerning quercetin utilization is its low
bioavailability. Therefore, solutions to the issues concerning its use such as
alteration of the molecular structure and combination therapy are in the
exploratory stage. In the present review, the most important aspects of
chemotherapeutic and chemopreventive effects, mechanisms and clinical application
potential of quercetin in prostate cancer are summarized.
PMID- 25845381
TI - Biological Control of Patulin by Antagonistic Yeast: A case study and possible
model.
AB - The occurrence of patulin in fresh apples and apple products is a great burden
from health, safety and economic perspectives. Attempts to prevent patulin
accumulation in fruits might lead to the excessive use of fungicides. Therefore,
guaranteeing the safety of apple foods is crucial for the international apple
industry. Recently, literature revealed that application of antagonistic yeasts
and other BCAs have been able to disrupt the process of fungal infection and
patulin production in apples. Although, over the years the effect of interaction
between BCAs and fungi on patulin production has been reported, the exact
mechanism(s) of their action remain unclear. Here, the review focused on
toxicology and occurrence of PAT; research advances made over the past few years
on the interaction between antagonistic yeast, fruits and patulin-producing
fungi; the prevalence of patulin in apple fruits and products and the
implications of synthetic-fungicide applications. In addition, attention was
focused on the mechanism(s) and the enhancement of the biocontrol efficacy of
antagonistic for patulin control.
PMID- 25845382
TI - Inhibitory effects of proton beam irradiation on integrin expression and
signaling pathway in human colon carcinoma HT29 cells.
AB - Proton radiotherapy has been established as a highly effective modality used in
the local control of tumor growth. Although proton radiotherapy is used worldwide
to treat several types of cancer clinically with great success due to superior
targeting and energy deposition, the detailed regulatory mechanisms underlying
the functions of proton radiation are not yet well understood. Accordingly, in
the present study, to assess the effects of proton beam on integrin-mediated
signaling pathways, we investigated the expression of integrins related to tumor
progression and integrin trafficking, and key molecules related to cell adhesion,
as well as examining phosphorylation of signaling molecules involved in integrin
mediated signaling pathways. Proton beam irradiation inhibited the increase in 12
O-tetradecanoylphorbol-13-acetate (TPA)-induced integrin beta1 protein expression
and the gene expression of members of the integrin family, such as alpha5beta1,
alpha6beta4, alphavbeta3, and alphavbeta6 in human colorectal adenocarcinoma HT
29 cells. Simultaneously, the gene expression of cell adhesion molecules, such as
FAK and CDH1, and integrin trafficking regulators, such as RAB4, RAB11, and HAX1,
was decreased by proton beam irradiation. Moreover, proton beam irradiation
decreased the phosphorylation of key molecules involved in integrin signaling,
such as FAK, Src, and p130Cas, as well as PKC and MAPK, which are known as
promoters of cell migration, while increased the phosphorylation of AMPK and the
gene expression of Rab IP4 involved in the inhibition of cell adhesion and cell
spreading. Taken together, our findings suggest that proton beam irradiation can
inhibit metastatic potential, including cell adhesion and migration, by
modulating the gene expression of molecules involved in integrin trafficking and
integrin-mediated signaling, which are necessary for tumor progression.
PMID- 25845384
TI - Particulate matter 2.5 induces autophagy via inhibition of the
phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin kinase signaling
pathway in human bronchial epithelial cells.
AB - Particulate matter 2.5 (PM2.5) is a significant risk factor for asthma. A recent
study revealed that autophagy was associated with asthma pathogenesis. However,
the specific mechanisms underlying PM2.5-induced autophagy in asthma have
remained elusive. In the present study, PM2.5-induced autophagy was evaluated in
Beas-2B human bronchial epithelial cells and the potential molecular mechanisms
were investigated. Using electron microscopy, immunofluorescence staining and
immunoblot studies, it was confirmed that PM2.5 induced autophagy in Beas-2B
cells as a result of PM2.5-mediated inhibition of the phosphatidylinositol 3
kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in Beas-2B cells.
LY294002, a PI3K inhibitor, reduced the accumulation of microtubule-associated
protein 1 light chain 3 II and attenuated the effect of PM2.5. Phosphorylated (p
)p38, p-extracellular signal-regulated kinase and p-c-Jun N-terminal kinase were
dephosphorylated following exposure to PM2.5. The roles of p53, reactive oxygen
species scavenger tetramethylthiourea and autophagy inhibitor 3-methyladenine in
PM2.5-induced autophagy in Beas-2B cells were also investigated. The results
suggested that the PI3K/Akt/mTOR signaling pathway may be a key contributor to
PM2.5-induced autophagy in Beas-2B cells. The results of the present study
therefore provided an a insight into potential future clinical applications
targeting these signaling pathways, for the prevention and/or treatment of PM2.5
induced lung diseases.
PMID- 25845385
TI - Sequence and organization of the complete mitochondrial genome of the marsh tit
Poecile palustris (Aves: Paridae).
AB - The complete mitochondrial genome of the marsh tit Poecile palustris (Linnaeus,
1758) was sequenced using a combined Illumina and Sanger sequencing approach.
Using the known sequence of Poecile atricapillus Linnaeus, 1766 (Paridae)
homologous NGS reads were identified and assembled. The genome is 16,824 bp in
length and includes 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer
RNA genes and a control region. Gene order resembles that of the standard avian
gene order. The base composition of the genome is A (29.15%), T (22.50%), C
(33.61%) and G (14.73%). The control region between tRNA(Glu) and tRNA(Phe) is
composed of 1240 bp with no obvious repetitive motifs.
PMID- 25845383
TI - Long-term health consequences of premature or early menopause and considerations
for management.
AB - AIM: To review the current evidence concerning the long-term harmful effects of
premature or early menopause, and to discuss some of the clinical implications.
MATERIAL AND METHODS: Narrative review of the literature. RESULTS: Women
undergoing premature or early menopause, either following bilateral salpingo
oophorectomy or because of primary ovarian insufficiency, experience the early
loss of estrogen and other ovarian hormones. The long-term consequences of
premature or early menopause include adverse effects on cognition, mood,
cardiovascular, bone, and sexual health, as well as an increased risk of early
mortality. The use of hormone therapy has been shown to lessen some, although not
all of these risks. Therefore, multiple medical societies recommend providing
hormone therapy at least until the natural age of menopause. It is important to
individualize hormone therapy for women with early estrogen deficiency, and
higher dosages may be needed to approximate physiological concentrations found in
premenopausal women. It is also important to address the psychological impact of
early menopause and to review the options for fertility and the potential need
for contraception, if the ovaries are intact. CONCLUSIONS: Women who undergo
premature or early menopause should receive individualized hormone therapy and
counseling.
PMID- 25845386
TI - Mitochondrial DNA alterations correlate with the pathological status and the
immunological ER, PR, HER-2/neu, p53 and Ki-67 expression in breast invasive
ductal carcinoma.
AB - We analyzed the changes in mitochondrial DNA (mtDNA) copy numbers and the
shifting of mtDNA D310 sequence variations (D310 mutation) with their
relationships to pathological status and the expression levels of estrogen
receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor
2 (HER-2/neu), tumor-suppressor protein p53 and cellular proliferation protein Ki
67 in breast invasive ductal carcinoma (BIDC), respectively. Fifty-one paraffin
embedded BIDCs and their paired non-cancerous breast tissues were dissected for
DNA extraction. The mtDNA copy number and mtDNA D310 sequence variations were
determined by quantitative real-time polymerase chain reaction (q-PCR) and PCR
based direct sequencing, respectively. The expression levels of ER, PR, HER
2/neu, p53 and Ki-67 were determined by immunohistochemical (IHC) staining.
Compared to the paired non-cancerous breast tissues, 24 (47.1%) BIDCs had
elevated mtDNA copy numbers and 29 (56.9%) harbored mtDNA D310 mutations.
Advanced T-status (p=0.056), negative-ER (p=0.005), negative-PR (p=0.007),
positive-p53 (p=0.050) and higher Ki-67 (p=0.004) expressions were related to a
higher mtDNA copy ratio. In addition, advanced T-status (p=0.019) and negative
HER-2/neu expression (p=0.061) were associated with mtDNA D310 mutations. In
conclusion, higher mtDNA copy ratio and D310 mutations may be relevant biomarkers
correlated with pathological T-status and the expression levels of ER, PR, HER
2/neu, p53 and Ki-67 in BIDCs.
PMID- 25845387
TI - Long non-coding RNA ANRIL predicts poor prognosis and promotes
invasion/metastasis in serous ovarian cancer.
AB - Recent studies have highlighted the role of long non-coding RNAs (lncRNAs) in
carcinogenesis and have suggested that genes of this class might be used as
biomarkers in cancer. However, whether lncRNAs are involved in serous ovarian
cancer (SOC) remains largely unknown. In the present study, we focused on lncRNA
antisense non-coding RNA in the INK4 locus (ANRIL) and investigated its
expression pattern, clinical significance, and biological function in SOC. We
found that ANRIL levels were elevated in SOC tissues compared with normal
controls and were highly correlated with advanced FIGO stage, high histological
grade, lymph node metastasis, and poor prognosis. Multivariate analysis further
revealed that ANRIL is an independent prognostic factor for predicting overall
survival of SOC patients. In vitro, we compared differential ANRIL levels between
SOC parental cell lines (SK-OV-3, HO8910) and highly metastatic sublines (SK-OV
3.ip1, HO8910-PM). Notably, ANRIL was highly expressed in both SK-OV-3.ip1 cells
and HO8910-PM cells. SiRNA-mediated ANRIL silencing in these cells impaired cell
migration and invasion. Based on the metastasis-related mRNA microarray analysis
and subsequent western blotting confirmation, we found that MET and MMP3 are key
downstream genes of ANRIL involved in SOC cell migration/invasion. Together, our
data suggest that lncRNA ANRIL plays an important role in SOC invasion/metastasis
and could represent a novel biomarker for predicting poor survival as well a
promising therapeutic target.
PMID- 25845388
TI - The utility of measuring anti-Mullerian hormone in predicting menopause.
AB - Menopause is a relevant phase in a woman's reproductive life. Accurate estimation
of the time of menopause could improve the preventive management of women's
health. Reproductive hormones reflect the activity of follicle pools and provide
information about ovarian aging. Anti-Mu llerian hormone (AMH) is secreted from
small antral follicles and its level is correlated to the ovarian reserve. AMH
declines with age, and data suggest that it can provide information on menopausal
age and reproductive lifespan. Serum AMH levels become low approximately 5 years
before the final menstrual period and are undetectable in postmenopausal women.
The majority of studies indicate that AMH is relatively stable throughout the
menstrual cycle; however, there are interindividual variabilites of serum AMH
concentration under different conditions. AMH is an independent predictor of time
to menopause. AMH coupled with age for menopause prediction provides stronger
information than using age alone. Ongoing research is focused on constructing a
multivariate model including AMH values, genes related to follicular recruitment
and maternal age of menopause that would predict more precisily time to
menopause.
PMID- 25845390
TI - HIV Type 1 Subtype A1 Dominates in Armenia.
AB - OBJECTIVE: There is scarce information about the molecular epidemiology of HIV
infection in Armenia (former USSR). The objective of this work was to estimate
the distribution of HIV-1 subtypes in this country and get any information about
HIV drug resistance in naIve patients. DESIGN: A joint study involving 78
patients was carried out in Yerevan, Armenia and Moscow, Russia in 2009-2013. The
cohort studies included mostly IDUs (28.2%) and heterosexuals (69.2%). RESULTS:
The phylogenetic analyses based on population sequencing of partial pol gene
found subtype A1 being the most prevalent (92.3%), followed by subtype B (3.9%).
The HIV-1 tropism inferred from env V3-loop sequences was determined in 27
samples, among them R5-tropic viruses were found in 13 (48.1%) patients and X4-
variants--in 14 (51.9%) patients. The prevalence of drug resistance in naive
patients was low (1.5%) with the only one mutation K219Q found. CONCLUSION: The
composition and distribution of HIV-1 genetic variants in Armenia are evidently
influenced by the Russian and other FSU countries epidemic, due to the
significant volume of Armenian migrant/re-emigrant flows. Continued surveillance
of HIV-1 circulating subtypes and drug resistance in Armenia is important for the
proper management of HIV infection in this country.
PMID- 25845389
TI - HIV Replication at Low Copy Number and its Correlation with the HIV Reservoir: A
Clinical Perspective.
AB - The efficacy of combination therapy (antiretroviral therapy--ARV) is demonstrated
by the high rates of viral suppression achieved in most treated HIV patients.
Whereas contemporary treatments may continuously suppress HIV replication, they
do not eliminate the latent reservoir, which can reactivate HIV infection if ARV
is discontinued. The persistence of HIV proviral DNA and infectious viruses in
CD4+ T cells and others cells has long been considered a major obstacle in
eradicating the HIV virus in treated patients. Moreover, recent studies have
demonstrated the persistence of HIV replication at low copies in most patients on
suppressive ARV. The source of this 'residual viraemia' and whether it declines
over years of therapy remain unknown. Similarly, little is known regarding the
biological relationships between the HIV reservoir and viral replication at low
copies. The question of whether this 'residual viraemia' represents active
replication or the release of non-productive virus from the reservoir has not
been adequately resolved. From a clinical perspective, both the quantification of
the HIV reservoir and the detection of low levels of replication in full
responder patients on prolonged ARV may provide important information regarding
the effectiveness of treatment and the eradication of HIV. To date, the
monitoring of these two parameters has been conducted only for research purposes;
the routine use of standardised tests procedure is lacking. This review aims to
assess the current data regarding the correlation between HIV replication at low
copies and the HIV reservoir and to provide useful information for clinicians.
PMID- 25845391
TI - HIV-1 Early Infant Diagnosis is an Effective Indicator of the Prevention of
Mother-to-Child Transmission Program Performance: Experience from Cameroon.
AB - BACKGROUND: Despite improvement in HIV prevention of mother-to-child transmission
(PMTCT), there are still over 1,500 African infants newly infected daily. PMTCT
elimination requires antiretroviral therapy (ART) throughout pregnancy and
breastfeeding periods, while early infant diagnosis (EID) of HIV implies early
treatment for those infected. Our study aimed at assessing the utility of EID
program data in evaluating the implementation of PMTCT program in Cameroon, and
in identifying the efficacy of existing PMTCT interventions and breastfeeding
options on the events of HIV vertical transmission. METHODS: A study was
conducted from 2010-2011 using PMTCT data from EID sites of six regions of
Cameroon. PMTCT ARV regimens, breastfeeding options, and the child's HIV DNA
polymerase chain reaction (PCR) results were recorded. Statistical analyses were
performed using Mann Whitney U and Fisher exact tests, with p<0.05 considered
significant. RESULTS: A total of 2,505 mother-child pairs received ART, resulting
is 4.3% (93) vertical transmission, against 31.3% (284/906) among mother-child
pairs without exposure to any PMTCT intervention; p<0.00001. A statistically
significant difference (p<0.00001) was also found between formula feeding (FF)
(5.9%) versus exclusive breastfeeding (EBF) (12.5%), as well as between EBF
versus mixed feeding (MF) (30%). With FF, when both mother-child pairs received
PMTCT, only 2.9% (47/1603) vertical transmission was recorded versus 19.9%
(48/241) for mother-child pairs without intervention; p<0.00001. Transmission
rates were similar across infant age range [2.7% (10/376) for age <=6 weeks,
versus 2.5% (43/1807) for age >6 weeks-6 months]. Interestingly, babies aged 6
weeks receiving FF showed a significantly lower transmission rate (3.2%, 9/277)
as compared to their counterparts with EBF (7.7%, 12/156); p<0.00001. CONCLUSION:
Using EID dataset, it appears that considerable reduction in HIV MTCT may be
achievable through access to ARV (option B+) and adequate infant feeding option
(especially FF) in Cameroon. EID programme is therefore an effective routine
approach for PMTCT programme evaluation in resource-limited settings.
PMID- 25845392
TI - Performance of Genotype MTBDRplus in the Detection of Resistance to Rifampicin
and Isoniazid Among Clinical Mycobacteria Isolates in Ilorin, Nigeria.
AB - BACKGROUND: Performance of Genotype MTBDRplus assay against Lowenstein Jensen
(LJ) proportion method of Drug Susceptibility Testing (DST) in detection of
resistance among clinical mycobacteria isolates to rifampicin (RMP) and isoniazid
(INH) was evaluated in Ilorin, Nigeria. METHODS: This retrospective study
characterized one hundred mycobacteria isolates from pulmonary TB patients,
stored on LJ medium and subcultured unto fresh LJ slants before being genotyped
using MTBDRplus assay. DST was performed on the isolates against RMP, INH,
Ethambutol and Streptomycin. RESULTS: Genotype MTBDRplus identified 97% and 3% of
the 100 isolates as Mycobacterium tuberculosis Complex (MTBC) and Non-Tuberculous
Mycobacteria (NTM) respectively. Fourteen of the isolates, (14%) were resistant
to RMP while 86% were sensitive by the genotypic method. Three of these 14 RMP
resistant isolates were NTMs while 11 were MTBC. Twelve (12%) of the 100 isolates
were resistant to INH. Three INH-resistant isolates were NTMs, and 9 were MTBC.
Phenotypically and genotypically, the 3 NTMs were resistant to RMP and INH and
ten of the 97 MTBC strains were RMP-resistant. One RMP-phenotypically-sensitive
strain was genotypically resistant to RMP. Six of the MTBC isolates were
resistant to both RMP and INH by both methods. Most mutations occurred in the S
531L and S315T1 codons of rpoB and KatG genes of RMP and INH, respectively.
CONCLUSION: The high specificity and positive predictive values recorded by
MTBDRplus in our study make it suitable for use in the programmatic management of
drug-resistant TB in resource-limited settings.
PMID- 25845393
TI - Socio-Demographic and Adherence Factors Associated with Viral Load Suppression in
HIV-Infected Adults Initiating Therapy in Northern Nigeria: A Randomized
Controlled Trial of a Peer Support Intervention.
AB - BACKGROUND: Virological suppression is the main goal of antiretroviral therapy.
To achieve this goal, efficient interventions that promote treatment adherence
are needed. This study was aimed at exploring the impact of peer-education on
virological outcomes in Northern Nigeria. METHODS: A randomized controlled trial
(RCT) among patients receiving antiretroviral treatment was conducted in 2 phases
between August 2006 and January 2008 in the "largely Muslim" Northern Nigeria.
Participants were randomized into one of three intervention arms: standard of
care arm, a second arm which included daily reminders via alarm and follow-up
calls from peer-educators, and adherence support by a home-based treatment
partner; and a third arm which included second arm activities, plus home visits
by peer-educators. We evaluated sociodemographic factors and adherence levels,
measured using self-report and pharmacy (Rx) refill rates, as risk factors for
viral load (VL) suppression. RESULTS: Of the 600 participants (43% males), 276
were observed till the end of the study. There were no significant differences in
mean log 10 VL between the intervention groups. At the end of entire follow-up
period, 83% (229/276) who were not lost to follow-up achieved undetectable VL (<
400 copies/ml). In the multivariable analysis, age between 30-34 years (vs 18-24
years) and both baseline CD4 ranges between 100-199 cells/mm(3) or 200-349
cells/mm(3) (vs CD4 <100 cells/mm(3)) as positively associated with VL
suppression while poor self-reported adherence and <95% Rx refill rates were
negatively associated with VL suppression. CONCLUSION: High levels of viral
suppression and low prevalence of drug resistance mutations (DRMs) were seen in
this cohort participating in an ART adherence study in Northern Nigeria. Self
reported good adherence and optimal Rx refill rates were reported as significant
predictors of VL suppression. Our findings indicate that ART adherence will
improve significantly regardless of whether HIV-infected adults received peer
education-based medication adherence interventions or standard of care services.
PMID- 25845394
TI - Carbon quantum dots and applications in photocatalytic energy conversion.
AB - Quantum dots (QDs) generally refer to nanoscale particles of conventional
semiconductors that are subject to the quantum-confinement effect, though other
nanomaterials of similar optical and redox properties are also named as QDs even
in the absence of strictly defined quantum confinement. Among such nanomaterials
that have attracted tremendous recent interest are carbon dots, which are small
carbon nanoparticles with some form of surface passivation, and graphene quantum
dots in various configurations. In this article, we highlight these carbon-based
QDs by focusing on their syntheses, on their photoexcited state properties and
redox processes, and on their applications as photocatalysts in visible-light
carbon dioxide reduction and in water-splitting, as well as on their mechanistic
similarities and differences.
PMID- 25845395
TI - Microencapsulation of recombinant adenovirus within poly-DL-lactide-poly(ethylene
glycol) microspheres for enhanced gene transfection efficiency and inhibitory
effects on hepatocellular carcinoma cells in vitro.
AB - When gene therapy is performed for the treatment of malignant tumors, gene
transfer efficiency and selectivity are highly important. Polymer vehicle
microspheres are a novel type of therapy, which have been developed rapidly in
recent years and are able to control drug release, prolong the biological half
life of drugs, decrease side effects and achieve targeted delivery. The present
study was designed to construct a polymer microsphere-encapsulated recombinant
adenovirus with human tissue inhibitors of the matrix metalloproteinase-1 (TIMP
1) gene, and to discuss its characterization for the purpose of liver cancer gene
therapy. The microsphere was prepared from biodegradable poly-DL-lactide
poly(ethylene glycol) (PELA) encapsulating rAdTIMP-1, the recombinant adenovirus
carrying TIMP-1, by a modified double-emulsion method. The particle morphology,
diameter, virus encapsulation, loading rate and release kinetics of the rAd
microspheres were determined in vitro. Hepatocellular carcinoma (HCC) HepG2 cells
were transfected with the rAd-microsphere and the efficiency of transfection was
assessed by fluorescent microscopy. The production and expression of TIMP-1 was
identified by gelatin zymography and western blot analysis, and the invasiveness
was detected by a matrigel matrix invasion assay. The microsphere encapsulating
rAdTIMP-1 was successfully constructed with a diameter of 1.965 MUm,
encapsulation efficiency of 60.0%, a viral load of 10.5 x 10(8)/mg, a virus
release of ~60% within 120 h and a total release time of >240 h. The resultant
rAd-microspheres were able to efficiently transfect HepG2 cells with the
transfection efficiency enhanced by ~90%. As a result, the transfected HepG2
cells had significantly increased TIMP-1 enzyme activity and the expression of
TIMP-1 was detected by western blot analysis. In addition, the proliferation and
invasion ability of the HCC cells was markedly inhibited by the rAd-microspheres.
The resultant rAd-microspheres, PELA-encapsulated recombinant TIMP-1 adenovirus,
had enhanced transfection efficiency and were able to markedly inhibit the in
vitro biological behavior of HepG2 cells. This provides an experimental basis for
this polymer application and may pave the way for prospective in vivo clinical
trials and further comprehensive therapy for liver cancer.
PMID- 25845397
TI - Reproducibility of Facial Soft Tissue Thickness Measurements Using Cone-Beam CT
Images According to the Measurement Methods.
AB - The purpose of this study was to establish the reproducibility of facial soft
tissue (ST) thickness measurements by comparing three different measurement
methods applied at 32 landmarks on three-dimensional cone-beam computed
tomography (CBCT) images. Two observers carried out the measurements of facial ST
thickness of 20 adult subjects using CBCT scan data, and inter- and intra
observer reproducibilities were evaluated. The measurement method of
"perpendicular to bone" resulted in high inter- and intra-observer
reproducibility at all 32 landmarks. In contrast, the "perpendicular to skin"
method and "direct" method, which measures a distance between one point on bone
and the other point on skin, presented low reproducibility. The results indicate
that reproducibility could be increased by identifying the landmarks on hard
tissue images, rather than on ST images, and the landmark description used in
this study can be used in the establishment of reliable tissue depth data using
CBCT images.
PMID- 25845396
TI - Circadian Tick-Talking Across the Neuroendocrine System and Suprachiasmatic
Nuclei Circuits: The Enigmatic Communication Between the Molecular and Electrical
Membrane Clocks.
AB - As with many processes in nature, appropriate timing in biological systems is of
paramount importance. In the neuroendocrine system, the efficacy of hormonal
influence on major bodily functions, such as reproduction, metabolism and growth,
relies on timely communication within and across many of the brain's homeostatic
systems. The activity of these circuits is tightly orchestrated with the animal's
internal physiological demands and external solar cycle by a master circadian
clock. In mammals, this master clock is located in the hypothalamic
suprachiasmatic nucleus (SCN), where the ensemble activity of thousands of clock
neurones generates and communicates circadian time cues to the rest of the brain
and body. Many regions of the brain, including areas with neuroendocrine
function, also contain local daily clocks that can provide feedback signals to
the SCN. Although much is known about the molecular processes underpinning
endogenous circadian rhythm generation in SCN neurones and, to a lesser extent,
extra-SCN cells, the electrical membrane clock that acts in partnership with the
molecular clockwork to communicate circadian timing across the brain is poorly
understood. The present review focuses on some circadian aspects of reproductive
neuroendocrinology and processes involved in circadian rhythm communication in
the SCN, aiming to identify key gaps in our knowledge of cross-talk between our
daily master clock and neuroendocrine function. The intention is to highlight our
surprisingly limited understanding of their interaction in the hope that this
will stimulate future work in these areas.
PMID- 25845398
TI - Nanoparticle Estrogen in Rat Spinal Cord Injury Elicits Rapid Anti-Inflammatory
Effects in Plasma, Cerebrospinal Fluid, and Tissue.
AB - Persons with spinal cord injury (SCI) are in need of effective therapeutics.
Estrogen (E2), as a steroid hormone, is a highly pleiotropic agent; with anti
inflammatory, anti-apoptotic, and neurotrophic properties, it is ideal for use in
treatment of patients with SCI. Safety concerns around the use of high doses of
E2 have limited clinical application, however. To address these concerns, low
doses of E2 (25 MUg and 2.5 MUg) were focally delivered to the injured spinal
cord using nanoparticles. A per-acute model (6 h after injury) was used to assess
nanoparticle release of E2 into damaged spinal cord tissue; in addition, E2 was
evaluated as a rapid anti-inflammatory. To assess inflammation, 27-plex
cytokine/chemokine arrays were conducted in plasma, cerebrospinal fluid (CSF),
and spinal cord tissue. A particular focus was placed on IL-6, GRO-KC, and MCP-1
as these have been identified from CSF in human studies as potential biomarkers
in SCI. S100beta, an additional proposed biomarker, was also assessed in spinal
cord tissue only. Tissue concentrations of E2 were double those found in the
plasma, indicating focal release. E2 showed rapid anti-inflammatory effects,
significantly reducing interleukin (IL)-6, GRO-KC, MCP-1, and S100beta in one or
all compartments. Numerous additional targets of rapid E2 modulation were
identified including: leptin, MIP-1alpha, IL-4, IL-2, IL-10, IFNgamma, tumor
necrosis factor-alpha, etc. These data further elucidate the rapid anti
inflammatory effects E2 exerts in an acute rat SCI model, have identified
additional targets of estrogen efficacy, and suggest nanoparticle delivered
estrogen may provide a safe and efficacious treatment option in persons with
acute SCI.
PMID- 25845399
TI - Sesamin inhibits lipopolysaccharide-induced proliferation and invasion through
the p38-MAPK and NF-kappaB signaling pathways in prostate cancer cells.
AB - Sesamin, a lipid-soluble lignan, is one of the major constituents of sesame.
Previous studies have reported that sesamin induces growth inhibition in human
cancer cells, particularly prostate cancer cells. In the present study, we mainly
explored the mechanism underlying the protective effect of sesamin on prostate
cancer cell proliferation and invasion induced by lipopolysaccharide (LPS). We
found that the proliferation of PC3 cells, as determined using the MTT assay, and
the expression of cyclin D1, COX-2, Bcl-2 and survivin proteins elevated by LPS
were distinctly inhibited by sesamin in a dose-dependent manner. Meanwhile, the
ability of PC3 cell invasion, as determined using the Transwell assay and the
expression of matrix metalloproteinase 9 (MMP-9), intercellular adhesion molecule
1 (ICAM-1) and vascular endothelial growth factor (VEGF) proteins increased by
LPS were obviously reduced by sesamin in a dose-dependent manner. In addition,
the accumulation of TGF-alpha and interleukin-6 (IL-6) production induced by LPS
in the culture supernatant was found to be decreased dose-dependently with
sesamin pretreatment in PC3 cells using the enzyme-linked immunosorbent assay
(ELISA) kit. Furthermore, phosphorylation of the p38 protein and nuclear factor
(NF)-kappaB activity in the PC3 cells were enhanced by LPS and further inhibited
with sesamin, SB203580 pretreatment or p38-siRNA transfection, respectively.
Sesamin or SB203580 pretreatment obviously inhibited PC3 cells-derived tumor
growth induced by LPS in vivo. Taken together, these results suggest that the
potential ability of sesamin to downregulate the secretion of cytokines and the
expression of cell proliferative- and invasive-related gene products induced by
LPS was shown to be via the p38 mitogen-activated protein kinase (p38-MAPK) and
NF-kappaB signaling pathways, which may be one of the mechanisms of the
anticancer activity of this sesamin agent in prostate cancer cells.
PMID- 25845400
TI - Polarized currents inhibit in vitro growth of bacteria colonizing cutaneous
ulcers.
AB - Infections caused by Staphylococcus aureus, Pseudomonas aeruginosa, and
Escherichia coli are among the microorganisms that often lead to infection in
pressure ulcers. Polarized current has emerged as a possible intervention to
limit bacterial proliferation. We analyzed the effect of fixed diphasic - Bernard
(FD-B) and high voltage monophasic pulsed (HVMP) currents on bacteria S. aureus
ATCC 25923 (Gram +), P. aeruginosa ATCC 27853 (Gram -), and E. coli ATCC 25922
(Gram -). After the bacterial strains were activated the bacteria were suspended
in physiological solution (0.9%) and the concentration adjusted to 1.5 * 10(3)
CFU/mL. The cultures were stimulated with FD-B current at (3, 6, and 9 mA, 100
Hz, 15 and 30 minutes) and HVMP (32, 64, and 95 V, 100 Hz, 30 and 60 min) while
monitoring the pH and temperature. After the stimulation, the suspensions were
plated and incubated for 24 hours at 37 degrees C. Then the counts were made of
colony forming units (CFU). Data were submitted to normality Shapiro-Wilk test
followed by nonparametric ANOVA test and post hoc Tukey test with p < 0.05. There
was a decrease in the CFU for the two currents, but the most effective reduction
was in FD-B. The temperature remained constant and the pH measured alkaline at
the negative pole and acid at the positive pole during stimulation. The
application of FD-B and HVMP currents promoted inhibition of bacterial
proliferation when stimulated in vitro, acting as an adjuvant resource in the
healing process.
PMID- 25845401
TI - Acute generalized exanthematous pustulosis following paracetamol ingestion in a
child.
PMID- 25845402
TI - Effects of ethanol exposure in utero on Cajal-Retzius cells in the developing
cortex.
AB - BACKGROUND: Prenatal exposure to ethanol exerts teratogenic effects on the
developing brain. Here, we tested the hypothesis that exposure to ethanol in
utero alters the disposition of Cajal-Retzius cells that play a key role in
orchestrating proliferation, migration, and laminar integration of cortical
neurons in the embryonic cortex. METHODS: Pregnant Ebf2-EGFP mice, harboring EGFP
fluorescent Cajal-Retzius cells, were subjected to a 2% w/w ethanol consumption
regimen starting at neural tube closure and lasting throughout gestation. Genesis
of Cajal-Retzius cells was assessed by means of 5-bromo-2-deoxyuridine (BrdU)
immunofluorescence at embryonic day 12.5, their counts and distribution were
determined between postnatal day (P)0 and P4, patch clamp electrophysiology was
performed between P2 and P3 to analyze GABA-mediated synaptic activity, and open
field behavioral testing was conducted in P45-P50 adolescents. RESULTS: In Ebf2
EGFP embryos exposed to ethanol in utero, we found increased BrdU labeling and
expanded distribution of Cajal-Retzius cells in the cortical hem, pointing to
increased genesis and proliferation. Postnatally, we found an increase in Cajal
Retzius cell number in cortical layer I. In addition, they displayed altered
patterning of spontaneous GABA-mediated synaptic barrages and enhanced GABA
mediated synaptic activity, suggesting enhanced GABAergic tone. CONCLUSIONS:
These findings, together, underscore that Cajal-Retzius cells contribute to the
ethanol-induced aberration of cortical development and abnormal GABAergic
neurotransmission at the impactful time when intracortical circuits form.
PMID- 25845403
TI - Advances in surgical treatment of chronic pancreatitis.
AB - The incidence of chronic pancreatitis (CP) is between 2 and 200 per 100,000
persons and shows an increasing trend year by year. India has the highest
incidence of CP in the world at approximately 114 to 200 per 100,000 persons. The
incidence of CP in China is approximately 13 per 100,000 persons. The aim of this
review is to assist surgeons in managing patients with CP in surgical treatment.
We conducted a PubMed search for "chronic pancreatitis" and "surgical treatment"
and reviewed relevant articles. On the basis of our review of the literature, we
found that CP cannot be completely cured. The purpose of surgical therapy for CP
is to relieve symptoms, especially pain; to improve the patient's quality of
life; and to treat complications. Decompression (drainage), resection,
neuroablation and decompression combined with resection are commonly used methods
for the surgical treatment of CP. Before developing a surgical regimen, surgeons
should comprehensively evaluate the patient's clinical manifestations, auxiliary
examination results and medical history to develop an individualized surgical
treatment regimen.
PMID- 25845404
TI - Bovine Circadian Locomotor Output Cycles Kaput (CLOCK) and Clusterin (CLU) mRNA
Quantitation in Ejaculated Crossbred Bull Spermatozoa.
AB - Mammalian circadian locomotor output cycles kaput (CLOCK) gene encodes a
transcription factor that affects both the persistence and the period of
circadian rhythms. Earlier reports suggested that CLOCK gene might be associated
with male infertility in human. Present investigation, for the first time,
reports that CLOCK gene expresses differentially between good and poor quality
crossbred bull semen. The relative expression of CLOCK was significantly (p <
0.05) higher among good quality bull semen than motility-impaired ones.
Clusterins (CLU) are series of genes associated with a variety of physiological
activities including spermatogenesis, apoptosis and degenerative disease
conditions. In the present context, we also investigated that the expression of
CLU gene was significantly (p < 0.05) higher among motility-impaired crossbred
bull semen compared to the good quality one.
PMID- 25845405
TI - 1064 nm Q-switched Nd:YAG laser for the treatment of Argyria: a systematic
review.
AB - Argyria is a benign skin disease characterized by blue to slate-grey
discoloration that is caused by deposition of silver granules in the skin and/or
mucus membranes as a result of long-term ingestion of ionized silver solutions or
exposure to airborne silver particles. The skin discoloration can be generalized
or localized and is exacerbated by sunlight. The skin discoloration is usually
permanent, and until recently, there has been no effective treatment for argyria.
Over the past 6 years, a number of case reports and one case series have
described cases of argyria that were successfully treated with a 1064 nm Q
switched (QS) neodymium-doped yttrium aluminium garnet (Nd:YAG) laser; however, a
review of these studies has never been reported in the dermatologic literature.
To review the use of the 1064 nm QS Nd:YAG laser for the treatment of argyria. A
search of the National Library of Medicine's PubMed Database and the SCOPUS
Database was performed to find articles that detailed the treatment of argyria
with 1064 nm QS Nd:YAG laser. Six articles were selected for inclusion in this
review. Each article was reviewed and summarized in a table. A 1064 nm QS Nd:YAG
laser offers a novel and effective treatment for argyria. A systematic review of
the dermatologic literature revealed a limited number of case reports and case
series using this treatment. However, the results gleaned by the authors from the
literature review provide important information to the clinician. For patients
with argyria, a single pass of the 1064 nm QS Nd:YAG laser offers immediate,
effective and sustained pigment clearing without any long-term adverse effects.
PMID- 25845406
TI - Efficacy and safety of non-hormonal remedies for vaginal dryness: open,
prospective, randomized trial.
AB - OBJECTIVES: To prove non-inferiority of the first non-hormonal vaginal cream in
Germany, Vagisan((r)) Moisturising Cream (CREAM), compared to a non-hormonal
vaginal gel (GEL) for vulvovaginal atrophy (VVA) symptom relief. METHOD: This was
a 12-week multicenter, open-label, prospective, randomized, two-period, cross
over phase-III trial. The primary endpoint was the cumulative VVA subjective
symptom score of the respective treatment period. Secondary endpoints were
assessment of single VVA subjective and objective symptoms, VVA objective symptom
score, vaginal pH, safety parameters, overall assessment of efficacy,
tolerability and evaluation of product properties. In total, 117 women were
randomly allocated to either one of the two treatments, each administered for 4
weeks; 92 women were included in the per-protocol analysis (primary analysis).
The main outcome measure was cumulative VVA subjective symptom score. RESULTS:
Regarding VVA symptom relief, results confirmed non-inferiority of CREAM compared
to GEL and even indicated superiority of CREAM. Frequency and intensity of
subjective symptoms and objective findings were clearly reduced, with CREAM
showing better results compared to GEL. Mean VVA objective symptom score
significantly decreased; improvement was significantly greater with CREAM.
Vaginal pH decreased only following CREAM treatment. Tolerability was superior
for CREAM: burning and itching, mostly rated as mild, occurred markedly less
often with CREAM than with GEL. Overall satisfaction with treatment efficacy,
tolerability and most product properties were rated significantly superior for
CREAM. CONCLUSIONS: Subjective and objective VVA symptoms were reliably and
safely reduced by both non-hormonal topical products. However, efficacy and
tolerability of CREAM were shown to be superior to GEL.
PMID- 25845408
TI - Blending qualitative and quantitative research methods to optimize patient
reported outcome measures (PROMs).
PMID- 25845407
TI - HIV and HCV Medications in End-Stage Renal Disease.
AB - Human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV)
infection affect populations worldwide. With the availability of over 35 Food and
Drug Administration approved medications for treatment of HIV, the morbidity and
mortality associated with HIV has greatly improved. On the other hand, treatment
options for HCV have been limited until very recently. While the use of protease
inhibitors (such as boceprevir and telaprevir) has become standard of care for
treatment of hepatitis C in the general population, data for individuals with
impaired kidney function, particularly those on dialysis, are extremely limited.
Use of medications in dialysis patients can be challenging given the dose
adjustments that must be made for renally cleared molecules, and potentially
increased impact of adverse effects such as anemia. Recommendations for dosing of
marketed therapies for HIV and HCV are reviewed.
PMID- 25845409
TI - Cumulative risk disparities in children's neurocognitive functioning: a
developmental cascade model.
AB - The current longitudinal study examined the role of cumulative social risk on
children's theory of mind (ToM) and executive functioning (EF) across early
development. Further, we also tested a cascade model of development in which
children's social cognition at 18 months was hypothesized to predict ToM and EF
at age 4.5 through intermediary language skills at age 3. We then examined
whether this developmental mechanism varied as a function of social risk status.
Participants were 501 children recruited when they were newborns, at which point
eight psychosocial risk factors were assessed and combined into a metric of
cumulative social disadvantage. Families were followed up at 18 months, at which
point four social-cognitive skills were assessed using developmentally sensitive
tasks: joint attention, empathy, cooperation, and self-recognition. Language was
measured at age 3 using a standardized measure of receptive vocabulary. At age 3
and 4.5, EF and ToM were measured using previously validated tasks. Results
showed that there were notable cumulative risk disparities in overall
neurocognitive skill development, and these effects became more differentiated
over time. Support was also found for a developmental mechanism wherein the
effect of social cognition at 18 months on ToM and EF in the preschool period
operated specifically through children's receptive language ability at age 3.
This pathway functioned similarly for children with both low- and high-risk
backgrounds. These results extend previous findings by documenting the role of
cumulative social disadvantage on children's neurocognition and the pathways that
link key neurocognitive abilities across early development.
PMID- 25845410
TI - Differential regulation of toxoflavin production and its role in the enhanced
virulence of Burkholderia gladioli.
AB - Burkholderia gladioli is a causal agent of bacterial panicle blight and
sheath/grain browning in rice in many countries. Many strains produce the yellow
pigment toxoflavin, which is highly toxic to plants, fungi, animals and
microorganisms. Although there have been several studies on the toxoflavin
biosynthesis system of B. glumae, it is still unclear how B. gladioli activates
toxoflavin biosynthesis. In this study, we explored the genomic organization of
the toxoflavin system of B. gladioli and its biological functions using
comparative genomic analysis between toxoflavin-producing strains (B. glumae BGR1
and B. gladioli BSR3) and a strain not producing toxoflavin (B. gladioli
KACC11889). The latter exhibits normal physiological characteristics similar to
other B. gladioli strains. Burkholderia gladioli KACC11889 possesses all the
genes involved in toxoflavin biosynthesis, but lacks the quorum-sensing (QS)
system that functions as an on/off switch for toxoflavin biosynthesis. These data
suggest that B. gladioli has evolved to use the QS signalling cascade of
toxoflavin production (TofI/TofR of QS -> ToxJ or ToxR -> tox operons) similar to
that in B. glumae. However, some strains may have evolved to eliminate toxoflavin
production through deletion of the QS genes. In addition, we demonstrate that the
toxoflavin biosynthetic system enhances the virulence of B. gladioli. These
findings provide another line of evidence supporting the differential regulation
of the toxoflavin system in Burkholderia strains.
PMID- 25845411
TI - Identification and functional expression of genes encoding flavonoid O- and C
glycosidases in intestinal bacteria.
AB - Gut bacteria play a crucial role in the metabolism of dietary flavonoids and
thereby influence the bioactivity of these compounds in the host. The intestinal
Lachnospiraceae strain CG19-1 and Eubacterium cellulosolvens are able to
deglycosylate C- and O-coupled flavonoid glucosides. Growth of strain CG19-1 in
the presence of the isoflavone C-glucoside puerarin (daidzein 8-C-glucoside) led
to the induction of two proteins (DfgC, DfgD). Heterologous expression of the
encoding genes (dfgC, dfgD) in Escherichia coli revealed no C-deglycosylating
activity in the resulting cell extracts but cleavage of flavonoid O-glucosides
such as daidzin (daidzein 7-O-glucoside). The recombinant DfgC and DfgD proteins
were purified and characterized with respect to their quaternary structure,
substrate and cofactor specificity. The products of the corresponding genes
(dfgC, dfgD) from E. cellulosolvens also catalysed the O-deglycosylation of
daidzin following their expression in E. coli. In combination with three
recombinant proteins encoded by adjacent genes in E. cellulosolvens (dfgA, dfgB,
dfgE), DfgC and DfgD from E. cellulosolvens catalysed the deglycosylation of the
flavone C-glucosides homoorientin (luteolin 6-C-glucoside) and isovitexin
(apigenin 6-C-glucoside). Even intact cells of E. coli expressing the five E.
cellulosolvens genes cleaved these flavone C-glucosides and, also, flavonoid O
glucosides to the corresponding aglycones.
PMID- 25845413
TI - Individual prevention courses for occupational skin diseases: changes in and
relationships between proximal and distal outcomes.
AB - BACKGROUND: To treat people with occupational contact dermatitis, the German
Accident Prevention and Insurance Association in the Health and Welfare Services
offers 2-day individual prevention (IP) seminars. OBJECTIVES: We investigated
whether there are short-term and medium-term changes in proximal (e.g. behaviour)
and distal (e.g. symptoms) outcomes after an IP seminar, whether changes in
proximal outcomes are associated with changes in distal outcomes, and whether
subgroups can be identified that benefit in particular.
PATIENTS/MATERIALS/METHODS: In a prospective study, 502 participants of 85 IP
courses completed the health education impact questionnaire (heiQTM) and skin
symptom questionnaire (Skindex-29) at the start of the course, immediately
thereafter, and after 6 months. Change was assessed according to standardized
effect size. Regression techniques were used to analyse associations between
proximal and distal outcomes. RESULTS: After 6 months, participants showed
improved self-management skills and preventive behaviour, and less fear of job
loss, disease-related symptoms, and emotional distress. Significant associations
between proximal and distal outcomes were found. Participants who felt more
limited by their skin disease showed greater effects. CONCLUSIONS: The results
are consistent with the assumption that IP courses provide a range of benefits
for people with occupational contact dermatitis. Changes in distal outcomes may
be influenced by changes in proximal outcomes.
PMID- 25845412
TI - Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a
multicenter cohort study.
AB - BACKGROUND: The treatment of splanchnic vein thrombosis (SVT) is challenging, due
to the increased risk of bleeding and potentially life-threatening complications.
Current recommendations are based on evidence from the treatment of venous
thrombosis in usual sites, but small observational studies in SVT population
suggest that the bleeding risk may offset the benefit of anticoagulant treatment
in this setting. The aim of this study was to evaluate the safety of vitamin K
antagonists (VKAs) in SVT patients. METHODS: We retrospectively included SVT
patients treated with VKAs followed by 37 Italian anticoagulation clinics, until
June 2013. The primary outcome was the incidence of major bleeding (MB),
according to the ISTH definition, during VKA treatment. Vascular events,
including both arterial and venous thrombosis, and mortality were also
documented. RESULTS: Three hundred and seventy-five patients were included
(median age 53 years; 54.7% males). During a median VKA treatment duration of
1.98 years, 15 MB events occurred, corresponding to an incidence rate of 1.24
(95% confidence interval [CI], 0.75-2.06) per 100 patient-years. Gastrointestinal
bleeding represented 40% of all MB events. At multivariate analysis, the presence
of esophageal varices emerged as independent predictor of MB (hazard ratio 5.4;
95% CI, 1.4-21.1). The incidence rate of vascular events on treatment was 1.37
(95% CI, 0.84-2.23) per 100 patient-years and the mortality rate was 0.83 (95%
CI, 0.44-1.54) per 100 patient-years. CONCLUSIONS: Selected SVT patients followed
by anticoagulation clinics for the management of VKA treatment show a low rate of
major bleeding and vascular events.
PMID- 25845414
TI - Adalimumab-Induced Cutaneous Lupus Erythematosus in a 16-Year-Old Girl with
Juvenile Idiopathic Arthritis.
AB - Tumor necrosis factor alpha (TNF-alpha) antagonists are used in the treatment of
numerous autoimmune conditions. Adalimumab is the first monoclonal antibody to
TNF-alpha and is used to treat juvenile idiopathic arthritis. A growing body of
literature associates anti-TNF-alpha therapies with several adverse dermatologic
manifestations, including drug-induced lupus erythematosus (LE). We describe a
case of cutaneous LE in a 16-year-old girl treated with adalimumab for juvenile
idiopathic arthritis. The temporal association between her presenting symptoms
and adalimumab initiation and gradual improvement after stopping biologic therapy
suggest adalimumab-induced cutaneous LE. With increasing use of anti-TNF
therapies in children, the potential for drug-induced LE should not be
overlooked.
PMID- 25845415
TI - Reply on recommendations for postpartum hemorrhage in women who decline blood
transfusion.
PMID- 25845416
TI - The Role of Attachment Style in Predicting Repetition of Adolescent Self-Harm: A
Longitudinal Study.
AB - This study investigated whether insecure attachment is associated with poorer
outcomes at 6-month follow-up in adolescents who self-harm. At baseline the Child
Attachment Interview was administered to 52 adolescents (13-17 years) referred to
specialist child and adolescent mental health services and with a recent history
of self-harm. Participants also completed self-report measures of self-harm, peer
attachment, anxiety, and depression and were administered the means end problem
solving task. Self-harm behavior and problem-solving skills were assessed again
at 6-month follow-up. At baseline, 14 (27%) were securely attached to their
mothers. In the 49 (94%) adolescents followed-up, those with insecure maternal
attachment and insecure peer attachment were more likely to have repeated self
harm. In addition, securely attached adolescents showed greater improvement in
problem-solving skills. These findings indicate that secure maternal and peer
attachments may help recovery from self-harm, possibly by supporting the
acquisition of problem-solving skills, and highlights the importance of social
connections and attachments for youth with a history of self-harm.
PMID- 25845417
TI - The association between the serum levels of uric acid and alanine
aminotransferase in a population-based cohort.
AB - BACKGROUND & AIMS: Elevated serum uric acid levels reflect and also cause both
oxidative stress and insulin resistance and are frequently observed in patients
with the metabolic syndrome. A strong association exists between the metabolic
syndrome and non-alcoholic fatty liver disease (NAFLD). Therefore, we aimed to
test the association between uric acid and elevated alanine aminotransferase
(ALT), as a surrogate for NAFLD, using real-world data. METHODS: Data used for
the cross-sectional study were obtained from Maccabi Healthcare System, a 2
million member health maintenance organization in Israel. The population
consisted of individuals aged 20-60 years who underwent blood tests for ALT and
uric acid between 1997 and 2012. Individuals with secondary liver disease,
celiac, and inflammatory bowel-disease were excluded. Subgroup analysis was
performed in subjects who were given the diagnosis of fatty liver in their
medical records (n = 2628). RESULTS: The study population included 82,608 people
(32.5% men, mean age 43.91 +/- 10.15 years). There was a significant positive
dose-response association between serum uric acid levels and the rate of elevated
serum ALT (P for trend <0.001). In multivariable model, controlling for potential
confounders, the association between uric acid and elevated ALT persisted (OR =
2.10, 95% CI 1.93-2.29, for the fourth quartile vs. the first). This association
was maintained in all categories of gender and BMI. Similar results were observed
among patients diagnosed with fatty liver (OR = 1.77, 1.22-2.57). CONCLUSIONS:
Serum uric acid is independently associated with elevated ALT, as a surrogate for
NAFLD, and thus may serve as a serum marker for liver damage and should be
further investigated as a risk factor for NAFLD.
PMID- 25845419
TI - Pulsed intravenous immunoglobulin therapy in refractory ulcerated livedoid
vasculopathy: seven cases and a literature review.
AB - Livedoid vasculopathy (LV) is a thrombotic vasculopathy of the skin of unknown
origin. No treatment has been validated in this indication, but case reports
demonstrated successful use of intravenous immunoglobulins (IVIg) in LV. We
assessed the efficacy and tolerability of 2 g/kg IVIg therapy every month for 2~3
cycles in patients with refractory LV. We analyzed the efficacy, side effects and
recurrence after long-term follow-up (51.9 +/- 14.0 months) in seven patients
with LV treated with 2 g/kg of IVIg. Mean clinical score of sum of erythema,
ulceration and pain index (each: 0-3) was 5.7 +/- 0.9 before the therapy and
significantly lower after therapy (1.1 +/- 0.5) (p = 0.001). Even after just one
cycle of IVIg, the score decreased significantly from 5.7 +/- 0.9 to 3.7 +/- 0.9
(p = 0.002), especially the pain score. In one patient, LV has not recurred for
over 7 years; six patients experienced recurrence after a mean of 12.7 +/- 2.8
months. Out of the six patients, two patients were re-administered IVIg whereas
the others were well controlled by conventional therapy. We propose that IVIg is
a rapid, effective, and safe therapeutic option in LV refractory to other
treatment modalities.
PMID- 25845418
TI - Increased lymphocyte apoptosis in mouse models of colitis upon ABT-737 treatment
is dependent upon BIM expression.
AB - Exaggerated activation of lymphocytes contributes to the pathogenesis of
inflammatory bowel disease (IBD). Medical therapies are linked to the BCL-2
family-mediated apoptosis. Imbalance in BCL-2 family proteins may cause failure
in therapeutic responses. We investigated the role of BCL-2 inhibitor ABT-737 for
lymphocyte apoptosis in mice under inflammatory conditions. B.6129P2-interleukin
(IL)-10(tm1Cgn) /J (IL-10(-/-) ) weighing 25-30 g with ongoing colitis were used.
Fifty mg/kg/day ABT-737 was injected intraperitoneally (i.p.). Haematological
analyses were performed with an ADVIA 2120 flow cytometer and mass cytometry with
a CyTOF 2. Following i.p. administration, ABT-737 was detected in both
spontaneous and acute colitis in peripheral blood (PBL) and colon tissue.
Treatment led to lymphopenia. CD4(+) CD44(+) CD62L(+) central memory and CD8(+) ,
CD44(+) CD62L(-) central memory T cells were decreased in PBL upon ABT-737
compared to vehicle-receiving controls. Increased apoptosis upon ABT-737 was
determined in blood lymphocytes, splenocytes and Peyer's patches and was
accompanied by a decrease in TNF and IL-1B. ABT-737 positively altered the
colonic mucosa and ameliorated inflammation, as shown by colonoscopy, histology
and colon length. A decreased BIM/BCL-2 ratio or absence of BIM in both Bim(-)
(/) (-) and Il10(-) (/) (-) * Bim(-) (/) (-) impeded the protective effect of ABT
737. The BIM/BCL-2 ratio decreased with age and during the course of treatment.
Thus, long-term treatment resulted in adapted TNF levels and macroscopic mucosal
damage. ABT-737 was efficacious in diminishing lymphocytes and ameliorating
colitis in a BIM-dependent manner. Regulation of inappropriate survival of
lymphocytes by ABT-737 may provide a therapeutic strategy in IBD.
PMID- 25845420
TI - The relationship between renal volume and histology in obese and nonobese kidney
donors.
AB - BACKGROUND: Obesity and related kidney diseases have become a global epidemic
problem. However, the underlying pathogenesis of obesity-related renal diseases
has not been clearly understood. In this study, we explored the link between
renal volume (RV) determined by computed tomography (CT) and renal histology
together with functional parameters in an obese population. MATERIALS AND
METHODS: Eighty-two kidney donors who underwent CT for the measurement of kidney
volume and zero-hour renal biopsy for renal histology were included in this cross
sectional study. Protein creatinine clearance and eGFR were evaluated in 24-h
urine specimens as indicators of renal function. RESULTS: Mean body mass index
(BMI) was 28 +/- 4.2 kg/m(2); 32.9% (n = 27) were obese. Mean RV was 196 +/- 36
cm(3). RV was positively correlated with BMI, body surface area and creatinine
clearance and negatively with HDL-cholesterol in the whole population. Renal
function parameters of obese subjects were better, and their renal volumes were
higher compared with the nonobese subjects. In obese subjects, corrected RV was
positively correlated with glomerular filtration rate (r = 0.46, P = 0.01) and
negatively with sclerotic glomeruli (r = -0.38, P = 0.04) and chronicity index (r
= -0.43, P = 0.02). In adjusted ordinal logistic regression analysis, corrected
RV was significantly associated with chronicity index (OR: 0.96; P = 0.01).
CONCLUSIONS: In obese cases, decreased RV determined by CT is associated with
worse renal histology. In this population, kidney imaging techniques may provide
important clues about renal survival.
PMID- 25845421
TI - Design, synthesis, and biological evaluation of novel peptide Gly(3) -MC62
analogues as potential antidiabetic agents.
AB - Two series of conformationally constrained analogues from Gly(3) -MC62 were
designed by scanning the residues Lys(1) , Thr(2) , Met(4) , Lys(5) , Met(7,) and
Ala(8) with an i-(i + 2) lactam bridge consisting of a Glutamic acid-xaa-lysine
(Glu-Xaa-Lys) scaffold and a diproline fragment. They were synthesized and
evaluated for their antihyperglycemic effects. Through screening in normal and
mice with diabetes mellitus, peptides II-5, III-3, III-4, and III-5 showed
significant improvement in antihyperglycemic and antioxidative activities
compared with Gly(3) -MC62, especially the compound III-4. The primary mechanism
of the compounds (II-5, III-3, III-4, and III-5) underlying this effect is the
islet beta-cells against oxidative damage induced by STZ, and III-4-treated mice
showed considerable improvement in the preservation of beta cells in the
pancreatic islets of DM mice. These data suggested that III-4 could be candidate
for the future treatment of diabetes mellitus.
PMID- 25845422
TI - Bioinspired synthesis of fluorescent calcium carbonate/carbon dot hybrid
composites.
AB - Herein, we report a novel method to synthesise fluorescent calcium
carbonate/carbon dots (CaCO3/CDs) by simply mixing CaCl2 and Na2CO3 solutions in
the presence of CDs. There are two roles of CDs in this easy and cost-effective
biomimetic strategy, that is as the template to direct the formation and assembly
of calcite nanocrystals into hierarchical spheres with diameters in the range of
200-300 nm and simultaneously as the phosphor to enable the CaCO3 to emit blue
fluorescence under UV (365 nm) irradiation with a quantum yield of 56.2%. The
CaCO3/CD hybrid composites possessing unique fluorescence properties are
potentially useful in various applications.
PMID- 25845423
TI - Semiconductor-enhanced Raman scattering for highly robust SERS sensing: the case
of phosphate analysis.
AB - Quantitative analysis of phosphate anions was achieved by measurement of "turn
off" SERS based on the first-layer effect of a chemical mechanism. More
importantly, our results demonstrate that it is possible, by means of
semiconductor-enhanced Raman scattering, to enhance the SERS sensing performance
including stability and reproducibility.
PMID- 25845424
TI - Highly efficient and stable photocatalytic reduction of CO2 to CH4 over Ru loaded
NaTaO3.
AB - An efficient and stable photocatalytic activity was obtained over NaTaO3 by
introducing an electron donor (H2) into the CO2 reduction process with water.
Ru/NaTaO3 demonstrated the best activity (CH4 51.8 MUmol h(-1) g(-1)) and product
selectivity in converting CO2 to CH4.
PMID- 25845426
TI - Equilibration Kinetics and Chemical Diffusion of Indium-Doped TiO2.
AB - The present work reports the gas/solid equilibration kinetics for In-doped TiO2
(0.4 atom % In) at elevated temperatures (1023-1273 K) in the gas phase of
controlled oxygen activity [10(-13) Pa < p(O2) < 10(5) Pa]. Thus, the determined
chemical diffusion coefficient is considered in terms of a microdiffusion
coefficient that is reflective of the transport kinetics within very narrow
ranges of oxygen activities. In analogy to pure TiO2, the chemical diffusion
coefficient for In-doped TiO2 exhibits a maximum at the n-p transition point. The
activation energy of the chemical diffusion exhibits a decrease with temperature
from 200 kJ/mol at 1023 K to an insignificant value at 1273 K. This effect is
reflective of a segregation-induced electrical potential barrier blocking the
transport of defects. The absolute value of the chemical diffusion coefficient
for In-doped TiO2 is larger from that of pure TiO2 by a factor of approximately
10. The effect of indium on the diffusion rate is considered in terms of the
associated concentration of oxygen vacancies, which are formed in order to
satisfy the charge neutrality for In-doped TiO2.
PMID- 25845425
TI - Redox-responsive polycation-functionalized cotton cellulose nanocrystals for
effective cancer treatment.
AB - Carbon nanotubes have excellent penetrability and encapsulation efficiency in the
fields of drug and gene delivery. Because of their excellent physicochemical
properties, biocompatible rodlike cellulose nanocrystals (CNCs) were reportedly
expected to replace carbon nanotubes. In this work, CNCs from natural cotton wool
were functionalized with disulfide bond-linked poly(2-(dimethylamino)ethyl
methacrylate) (PDMAEMA) brushes for effective biomedical applications. A range of
CNC-graft-PDMAEMA vectors (termed as CNC-SS-PDs) with various molecular weights
of PDMAEMA were synthesized. Under reducible conditions, PDMAEMA chains can be
easily cleaved from CNCs. The gene condensation ability, reduction sensitivity,
cytotoxicity, gene transfection, and in vivo antitumor activities of CNC-SS-PDs
were investigated in detail. The CNC-SS-PDs exhibited good transfection
efficiencies and low cytotoxicities. The needlelike shape of CNCs had an
important effect on enhancing transfection efficiency. The antitumor effect of
CNC-SS-PDs was evaluated by a suicide gene/prodrug system (cytosine deaminase/5
fluorocytosine, CD/5-FC) in vitro and in vivo. This research demonstrates that
the functionalization of CNCs with redox-responsive polycations is an effective
method for developing novel gene delivery systems.
PMID- 25845427
TI - Epithelial-to-mesenchymal transition in paired human primary and recurrent
glioblastomas.
AB - Patients with highly malignant glioblastomas have a short median survival time
mainly due to aggressive relapses after therapeutic treatment. Beside others,
they achieve their progressive character via epithelial-to-mesenchymal transition
(EMT). However, comprehensive investigations on EMT in paired primary-recurrent
glioblastoma pairs are presently not available. Thus, in our present study we
examined the expression profile of different EMT-markers in 17 matched primary
and recurrent glioblastomas by qPCR and double-immunofluorescence stainings to
identify EMT marker expressing cell types. Additionally, we analyzed the
influence of temozolomide on EMT marker expression in vitro. In comparison to
primary tumors, expression of beta-catenin (p<0.05), Snail1 (p<0.05), Snail2/Slug
(p<0.05), biglycan (p<0.05) and Twist1 (p<0.01) was downregulated in recurrence
whereas L1CAM showed upregulation (p<0.05; qPCR). Expression of desmoplakin,
vimentin, fibronectin and TGF-beta1 with its receptors TGF-betaR1 and TGF-betaR2
was almost unchanged. Comparing each individual pair, five different 'EMT groups'
within our glioblastoma collective were identified according to the regulation of
mRNA expression of GFAP, desmoplakin, Snail1, Snail2, Twist1 and vimentin.
Additionally, double-stainings of EMT markers in combination with cell specific
markers (glial fibrillary acidic protein, CD11b, von Willebrand factor) revealed
that EMT markers were expressed in a complex pattern with all three cellular
types as possible sources. Temozolomide treatment significantly induced mRNA
expression of nearly all investigated EMT markers in T98G glioma cells. Thus, EMT
seems to be involved in glioma progression in a complex way requiring an
individualized analysis, and is influenced by commonly used therapeutic options
in glioma therapy.
PMID- 25845428
TI - Spatial neglect in a patient with logopenic progressive aphasia.
AB - Spatial neglect and extinction are induced by posterior superior temporal and
inferior parietal dysfunction. In patients with logopenic progressive aphasia
(LPA) these structures are often degenerated, but there are no reports of these
disorders being associated. A 53-year-old man with the signs of LPA revealed
right-sided spatial neglect on line bisection and drawing tests as well as
multimodal extinction. MRI showed left hemispheric posterior temporoparietal
atrophy. Since injury to the core structures for these aphasic and attentional
syndromes overlaps, patients with LPA should be screened for spatial neglect and
extinction.
PMID- 25845430
TI - Do All Patients Require Prophylactic Drainage After Gastrectomy for Gastric
Cancer? The Experience of a High-Volume Center.
AB - BACKGROUND: Although our previous randomized controlled trial showed that there
was no difference in postoperative complications after gastric cancer surgery
between patients with and without a prophylactic drains (PDs), PDs are commonly
used by most surgeons and at most institutions. However, these results have not
yet been validated elsewhere. The purpose of this study was to analyze the
incidence, characteristics, and risk factors for a postoperative percutaneous
catheter drainage (PCD) procedure after gastric cancer surgery when PDs were not
used. METHODS: We reviewed data from 1989 patients who underwent gastrectomy with
lymphadenectomy for gastric cancer with curative intent from January 2012 to
December 2013. RESULTS: The incidence of PCD in the abdomen was 1.8 % (22/1249)
and 9.1 % (67/740) in patients with and without PD, respectively. In the without
PD group, age [odds ratio (OR) 1.032; p = 0.013], male gender (OR for female
0.38; p = 0.005), open surgery (OR for minimally invasive surgery 0.16; p =
0.013), and longer operative time (OR 1.01; p < 0.001) were independent risk
factors for postoperative PCD in the abdomen. In the without-PD group, no
microbes were detected in the peritoneal fluid obtained by PCD in 72.1 % (44/61)
of patients who underwent PCD, and the most commonly identified organisms were
Escherichia coli and Candida albicans. CONCLUSION: Not using a PD increased the
risk of PCD postoperatively, but no microbes in peritoneal fluid were detected in
the most patients. Selective use of PD in patients during gastric cancer surgery
may be possible using our risk factor analysis.
PMID- 25845431
TI - Nodular Regenerative Hyperplasia in Patients Undergoing Liver Resection for
Colorectal Metastases After Chemotherapy: Risk Factors, Preoperative Assessment
and Clinical Impact.
AB - BACKGROUND: Nodular regenerative hyperplasia (NRH) is a severe form of
chemotherapy-related liver injury (CALI) that may worsen the short-term outcome
of liver resection (LR) for colorectal metastases (CRLM). The present study aimed
to clarify the incidence, risk factors, preoperative assessment, and clinical
impact of NRH. METHODS: Overall, 406 patients undergoing 478 LRs for CRLM after
chemotherapy between 2000 and 2012 were studied. All resection specimens were
reviewed. After Gomori staining, NRH was graded according to the Wanless score.
RESULTS: NRH was diagnosed in 87 (18.2 %) patients, grades 2-3 in 14 (2.9 %)
patients. At multivariate analysis, the prevalence of NRH was increased after
oxaliplatin administration (21.4 vs. 8.4 %; p = 0.003), and reduced by the
addition of bevacizumab (11.7 vs. 19.8 %; p = 0.020). Two parameters predicted
the presence of NRH: the APRI score (AST to platelet ratio index: 25.5 % if >0.36
vs. 9.8 % if <=0.36; p = 0.004), and the platelet count (63.6 % if <100 *
10(3)/mm(3) vs. 25.3 % if 100-200 * 10(3)/mm(3) vs. 11.9 % if >200 * 10(3)/mm(3);
p = 0.032). Ninety-day mortality and liver failure rates were 0.6 and 3.6 %. NRH
was an independent predictor of postoperative liver failure (9.2 % if present vs.
2.3 % if not present; p = 0.021). In patients with grades 2-3 NRH, the rate of
liver failure was 14.3 %, 25.0 % after major hepatectomy. No other forms of CALI
impacted short-term outcomes. CONCLUSIONS: NRH was the most relevant form of
CALI, increasing the risk of postoperative liver failure. Oxaliplatin increased
the incidence of NRH, while bevacizumab decreased it. The APRI score and platelet
count were useful tools for predicting NRH.
PMID- 25845433
TI - Optimized generation of survivin-specific cytotoxic T lymphocytes against lung
cancer.
AB - Cancer immunotherapy based on dendritic cells (DCs) that target survivin is a
promising strategy with potential clinical applications. However, the translation
of survivin-specific cytotoxic T-lymphocyte (CTL) immunotherapy into the clinical
setting has numerous challenges, including the low efficiency of the treatment.
The present study aimed to improve the efficiency of the treatment, and found
that treatment with interleukin 4 (IL-4)/granulocyte macrophage colony
stimulating factor (GM-CSF) and a combination of proinflammatory cytokines
significantly increased the antigen-presenting and -capture abilities of DCs that
expressed exogenous survivin. Furthermore, lipopolysaccharide (LPS) stimulation
enhanced the DC response to subsequent T-cell signals and the extent of T-cell
activation. In addition, the efficiency of surviving-specific CTLs was examined,
and high cytotoxicity against surviving-expressing A549 lung cancer cells was
observed. However, the cytotoxicity of CTLs was significantly reduced in A549
cells with silenced survivin expression. The present study provides a novel
method to optimize the generation of surviving-specific CTLs against lung cancer
cells, which may advance the translation of surviving-specific CTL immunotherapy
into clinical use for the treatment of cancer.
PMID- 25845434
TI - Epigallocatechin-3-gallate inhibits nicotine-induced migration and invasion by
the suppression of angiogenesis and epithelial-mesenchymal transition in non
small cell lung cancer cells.
AB - Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea
extract, has been found to have anticancer activities in various types of cancer.
However, the underlying mechanisms are not completely clear. In the present
study, the effects of EGCG on migration, invasion, angiogenesis and epithelial
mesenchymal transition (EMT) induced by nicotine in A549 non-small cell lung
cancer (NSCLC) cells were investigated, and the underlying molecular mechanisms
were preliminarily examined. The results showed that different concentrations of
EGCG significantly inhibited nicotine-induced migration and invasion. Moreover,
EGCG reversed the upregulation of HIF-1alpha, vascular endothelial growth factor
(VEGF), COX-2, p-Akt, p-ERK and vimentin protein levels and the downregulation of
p53 and beta-catenin protein levels mediated by nicotine in A549 cells, but had
no significant effect on their mRNA levels. Furthermore, EGCG markedly inhibited
HIF-1alpha-dependent angiogenesis induced by nicotine in vitro and in vivo, and
suppressed HIF-1alpha and VEGF protein expression induced by nicotine in A549
xenografts of nude mice. Taken together, the results indicated that EGCG
inhibited nicotine-induced angiogenesis and EMT, leading to migration and
invasion in A549 cells. The results of the present study suggested that EGCG can
be developed into a potential agent for the prevention and treatment of smoking
associated NSCLC.
PMID- 25845435
TI - Chronic inflammation in offspring of patients with type 2 diabetes and
albuminuria.
PMID- 25845432
TI - Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated
from Human Embryonic Stem Cells.
AB - Human embryonic stem cells can be differentiated in vitro into a wide variety of
progeny cells by addition of different morphogens and growth factors. Our aim was
to monitor the expression pattern of tight junction (TJ) components and various
cellular markers during differentiation of stem cell lines toward the hepatic
lineage. Human embryonic stem cell lines (HUES1, HUES9) were differentiated into
endoderm-like cells, and further differentiated to hepatocyte-like cells. Gene
expressions of Oct3/4, Nanog, alpha-fetoprotein, albumin, cytokeratins (CK-7, CK
8, CK-18, CK-19), ATP-binding cassette (ABC) transporters (ABCC2, ABCC7, ABCG2),
and various TJ components, including claudin-1, claudin-4, claudin-5, claudin-7,
and tricellulin, as well as an extracellular matrix component, agrin were
monitored during hepatic differentiation by real-time quantitative PCR. The
differentiated cells exhibit epithelial morphology and functional assessments
similar to that of hepatocytes. The expression level of stem cell marker genes
(Oct3/4 and Nanog) significantly and gradually decreased, while liver-associated
genes (alpha-fetoprotein, albumin) reached their highest expression at the end of
the differentiation. The endoderm-like cells expressed claudin-1, which declined
eventually. The expression levels of cholangiocyte markers including claudin-4,
CK-7, CK-19, and agrin gradually increased and reached their highest level at the
final stage of differentiation. In contrast, these cells did not express notable
level of claudin-7, CK-8 and tricellulin. The marker set used for monitoring
differentiation revealed both hepatocyte and cholangiocyte characteristics of the
differentiated cells at the final stage. This is the first report describing the
expression level changes of various TJ components, and underlining their
importance in hepatic differentiation.
PMID- 25845437
TI - Erratum to: High-resolution color-Doppler ultrasound for the study of skin
growths.
PMID- 25845436
TI - Behavioral effects of phencyclidine on nicotine self-administration and
reinstatement in the presence or absence of a visual stimulus in rats.
AB - RATIONALE: Tobacco use is a serious health problem in the USA, and this problem
is potentiated in patients with schizophrenia. The reward system is implicated in
schizophrenia and may contribute to the high comorbidity between nicotine use and
schizophrenia, but very little research has been done on the topic. The reward
enhancement effect of nicotine has been shown to be important in nicotine use,
but there have been no studies on this effect in animal models of schizophrenia.
OBJECTIVES: This study was designed to determine the effects of phencyclidine,
used to model negative symptoms of schizophrenia, on self-administration of
nicotine with or without a co-occurring sensory reinforcer [i.e., visual stimulus
(VS)] in rats. METHODS: Phencyclidine (2.0 mg/kg) was administered before each of
seven nicotine self-administration sessions (0.01 mg/kg/inf) after which rats (n
= 8-9 per group) were given 7 days of extinction without phencyclidine
pretreatment. Reinstatement using phencyclidine (2.0 mg/kg), nicotine (0.2
mg/kg), and yohimbine (1.25 mg/kg, a pharmacological stressor) was tested after
extinction to determine if previous exposure to phencyclidine would alter
reinstatement of active lever pressing. RESULTS: Phencyclidine initially
decreased nicotine self-administration but only in the groups with a concurrent
VS. This decrease in self-administration dissipated after 5 days. During
reinstatement, rats that had previously received phencyclidine during self
administration with a VS were more sensitive to stress-induced reinstatement than
any other group. CONCLUSIONS: These results show a transitory effect of
phencyclidine on nicotine self-administration. Phencyclidine may induce a
potential sensitivity to pharmacological stressors contributing to reinstatement
of nicotine.
PMID- 25845438
TI - Turkish and Moroccan Young Adults in the Netherlands: The Relationship Between
Acculturation and Psychological Problems.
AB - This study investigated the relationship between acculturation and psychological
problems in Turkish and Moroccan young adults living in the Netherlands. A sample
of 131 healthy young adults aged between 18 and 24 years old, with a Turkish or
Moroccan background was recruited using snowball sampling. Data on acculturation,
internalizing and externalizing problems, beliefs about psychological problems,
attributions of psychological problems and barriers to care were collected and
analyzed using Latent Class Analysis and multinomial logistic regression. Three
acculturation classes were identified in moderately to highly educated, healthy
Turkish or Moroccan young adults: integration, separation and diffusion. None of
the participants in the sample were marginalized or assimilated. Young adults
reporting diffuse acculturation reported more internalizing and externalizing
problems than those who were integrated or separated. Separated young adults
reported experiencing more practical barriers to care than integrated young
adults. Further research with a larger sample, including young adult migrants
using mental health services, is required to improve our understanding of
acculturation, psychological problems and barriers to care in this population.
Including experiences of discrimination in the model might improve our
understanding of the relationship between different forms of acculturation and
psychological problems.
PMID- 25845439
TI - The platypnea-orthodeoxia syndrome: an unusual case of dyspnea.
PMID- 25845440
TI - Protocadherins and hypothalamic development: do they play an unappreciated role?
AB - Normal brain development requires coordinated cell movements at precise times. It
has long been established that cell-cell adhesion proteins of the cadherin
superfamily are involved in the adhesion and sorting of cells during tissue
morphogenesis. In the present review, we focus on protocadherins, which form the
largest subfamily of the cadherin superfamily and mediate homophilic cell-cell
adhesion in the developing brain. These molecules are highly expressed during
neural development and the exact roles that they play are still emerging.
Although, historically, protocadherins were considered to provide mechanical and
chemical connections between adjacent cells, recent research suggests that they
may also serve as molecular identity markers of neurones to help guide cell
recognition and sorting, cell migration, outgrowth of neuronal processes, and
synapse formation. This phenomenon of single cell diversity stems, in part, from
the vast variation in protein structure, genomic organisation and molecular
function of the protocadherins. Although expression profiles and genetic
manipulations have provided evidence for the role of protocadherins in the
developing brain, we have only begun to construct a complete understanding of
protocadherin function. We examine our current understanding of how
protocadherins influence brain development and discuss the possible roles for
this large superfamily within the hypothalamus. We conclude that further research
into these underappreciated but vitally important genes will shed insight into
hypothalamic development and perhaps the underlying aetiology of neuroendocrine
disorders.
PMID- 25845441
TI - Forensic Applicability of Femur Subtrochanteric Shape to Ancestry Assessment in
Thai and White American Males.
AB - Ancestry assessment from the postcranial skeleton presents a significant
challenge to forensic anthropologists. However, metric dimensions of the femur
subtrochanteric region are believed to distinguish between individuals of Asian
and non-Asian descent. This study tests the discriminatory power of
subtrochanteric shape using modern samples of 128 Thai and 77 White American
males. Results indicate that the samples' platymeric index distributions are
significantly different (p<=0.001), with the Thai platymeric index range
generally lower and the White American range generally higher. While the
application of ancestry assessment methods developed from Native American
subtrochanteric data results in low correct classification rates for the Thai
sample (50.8-57.8%), adapting these methods to the current samples leads to
better classification. The Thai data may be more useful in forensic analysis than
previously published subtrochanteric data derived from Native American samples.
Adapting methods to include appropriate geographic and contemporaneous
populations increases the accuracy of femur subtrochanteric ancestry methods.
PMID- 25845442
TI - Honey dilution impact on in vitro wound healing: Normoxic and hypoxic condition.
AB - Honey is known as a popular healing agent against tropical infections and wounds.
However, the effects of honey dilutions on keratinocyte (HaCaT) wound healing
under hypoxic condition is still not explored. In this study, we examined whether
honey dilution have wound healing potential under hypoxic stress. The antioxidant
potential and healing efficacy of honey dilution on in vitro wound of human
epidermal keratinocyte (HaCaT cells) under hypoxia (3% O2 ), and normoxia is
explored by nitro blue tetrazolium assay. The cell survival % quantified by MTT
assay to select four honey dilutions like 10, 1, 0.1, and 0.01 v/v% and the
changes in cellular function was observed microscopically. Further, the cell
proliferation, migration, cell-cell adhesion, and relevant gene expression were
studied by flow cytometry, migration/scratch assay, immunocytochemistry, and
reverse transcription-polymerase chain reaction, respectively. The expression
pattern of cardinal molecular features viz. E-cadherin, cytoskeletal protein F
actin, p63, and hypoxia marker Hif 1alpha were examined. Honey dilution in 0.1%
v/v combat wound healing limitations in vitro under normoxia and hypoxia (3%).
Its wound healing potential was quantified by immunocytochemistry and real-time
PCR for the associated molecular features that were responsible for cell
proliferation and migration. Our data showed that honey dilution can be effective
in hypoxic wound healing. Additionally, it reduced superoxide generation and
supplied favorable bioambience for cell proliferation, migration, and
differentiation during hypoxic wound healing. These findings may reveal the
importance of honey as an alternative and cost effective therapeutic natural
product for wound healing in hypoxic condition.
PMID- 25845443
TI - Discontinuation rates of menopausal hormone therapy among postmenopausal women in
the post-WHI study era.
AB - OBJECTIVES: Many women are reluctant to take menopausal hormone therapy (MHT) and
discontinue the treatment within 12 months. The aim of this study was to
investigate the persistence rates of combined MHT in the last decade, reflecting
changes in the post-Women's Health Initiative era. METHODS: We analyzed 17 020
patients receiving combined MHT from 2004 to 2013 using the Disease Analyzer
database. RESULTS: After 12 months of follow-up, 44.6% and 33.5% of patients
receiving 1 mg and 2 mg, respectively, of oral combined MHT were still on
treatment (p < 0.0001). The persistence rate of patients receiving < 50 MUg of
transdermal MHT was 39.1% after 1 year of treatment and presented no differences
compared to patients receiving >= 50 MUg of transdermal MHT with a persistence
rate of 38.2%. MHT start in the years 2007-2009 was associated with higher
discontinuation rates (hazard ratio 1.04, p = 0.0709) than MHT start in the years
2010-2013 (hazard ratio 0.90, p = 0.0001). CONCLUSIONS: Our results indicate that
patients beginning their treatments in the years 2010-2013 were more treatment
persistent than patients beginning with MHT in the early years after publication
of the Women's Health Initiative study (2004-2009). Administration of low-dose
oral MHT and transdermal MHT is associated with increased persistency compared to
higher doses of oral MHT.
PMID- 25845444
TI - Convergence of theories of alcohol administration postanabolic stimulation on
mTOR signaling: lessons for exercise regimen.
PMID- 25845445
TI - A multinational study to compare prevalence of atopic dermatitis in the first
year of life.
AB - BACKGROUND: Atopic dermatitis (AD) is common in childhood, with peak prevalence
in early childhood. However, international comparisons of prevalence have focused
on older children. We analysed differences in prevalence rates of AD and the
associations with putative risk and protective factors, among infants in two
European and two Central American countries. METHODS: In 1-yr old infants
participating in the International Study of Wheezing in Infants (EISL),
prevalence of AD and putative risk and protective factors were assessed by a
questionnaire applied to parents. For each risk/protective factor summary, odds
ratios with 95% confidence intervals were calculated by means of random effects
meta-analysis. RESULTS: Data from 9803 infants were analysed. AD prevalence
varied from 10.6% (Valencia, Spain) to 28.2% (San Pedro Sula, Honduras). Average
AD prevalences were lower in Europe (14.2%) than in Central America (18.2%, p <
0.01). Consistent with older children, presence of siblings decreased (OR 0.82
[0.72-0.94]), whereas family history of asthma (OR 1.32 [1.10-1.59]), rhinitis
(OR 1.33 [1.14-1.54]) and atopic dermatitis (OR 2.40 [1.89-3.05]) increased the
risk of infantile AD. However, gender, family size, breastfeeding and socio
economic status were not associated with AD prevalence. CONCLUSIONS: This study
shows almost threefold differences in the prevalence of AD in infancy between
countries. Risk and protective factors involved in the expression of infantile AD
differ from those in older children, possibly suggesting a different
pathophysiology. There is a need for additional international epidemiological
surveys on AD in young children, the peak prevalence age of this condition.
PMID- 25845447
TI - Iatrogenic Atrial Septal Defect After Cryoballoon Pulmonary Vein Isolation.
PMID- 25845446
TI - Monitoring the Foetal Phase of Gestation in the Queen With a 12.5-MHz Ultrasound
Probe and Prediction of the Parturition by Combining the Measurements of Head and
Abdominal Diameters.
AB - Ten gestations in six domestic shorthair cats (Europeans) were monitored daily
during the foetal phase of gestation, from the 28th day after the first mating
until parturition, using ultrasound with a 12.5-MHz probe. The development of the
various organs over this period was recorded. The diameters of the head (HD) and
abdomen (AD) were measured. Skeletal calcification visible on ultrasound occurred
in a defined order between the 34th and 40th day of gestation. During the last 30
days of gestation, there was a significant correlation between HD and days before
parturition (DBP) (r(2) = 0.99) and between AD and DBP (r(2) = 0.98). The
following equations were obtained: DBP = -2.10*HD (mm) + 50.74; DBP = -1.01*AD
(mm) + 42.19. The confidence intervals were stable over the last 30 days of
gestation. For the HD, the confidence interval was +/-1 day in 53% of cases and
+/-2 days in 85% of cases. For the AD, the confidence interval was +/-1 day in
45% of cases and +/-2 days in 77% of cases. A table obtained by combining the HD
and AD measurements made it possible to estimate the date of parturition within 2
days with a reliability of over 85%.
PMID- 25845448
TI - Efficacy of Andolast in Mild to Moderate Asthma: A Randomized, Controlled, Double
Blind Multicenter Study (The Andast Trial).
AB - BACKGROUND: Andolast is a new airway specific anti-inflammatory agent. The aim of
the present multicentered, randomized, placebo controlled study is to investigate
whether andolast produces a therapeutic response greater than placebo in
asthmatic adult patients. METHODS: 549 symptomatic patients with mild or moderate
asthma were randomized to receive andolast at three different doses (2, 4, or 8
mg t.i.d.) or placebo for 12 weeks. Efficacy and safety were evaluated during
scheduled visits with pulmonary function tests, peak expiratory flow rate (PEFR),
symptoms diary and quality of life questionnaire. The primary outcome included
the changes (expressed as percent variation) from baseline of the forced
expiratory volume in one second (FEV1) absolute values after 12 weeks of
treatment. FINDINGS: One hundred and thirty one (131) patients were treated with
andolast at the dose of 2 mg t.i.d., 128 patients at the dose of 4 mg t.i.d., 144
at the dose of 8 mg t.i.d. and 146 with placebo. Andolast produced a dose
dependent significant improvement over placebo on airflow obstruction, as shown
by the changes in FEV1 (andolast 2, 4, 8 mg vs. placebo: p = 0.011), especially
in a subgroup of patients showing moderate airways obstruction (FEV1<80%pred).
The mean number of asthma control days and free days significantly increased, the
average number of inhaled puffs of short-acting alpha2-agonists used as rescue
medication was significantly reduced as compared with placebo. Andolast also
significantly decreased the incidence of asthma exacerbation episodes.
CONCLUSION: Andolast proved to be significantly more effective than placebo in
improving airflow, and in controlling asthma symptoms both during day and night.
PMID- 25845449
TI - A rapid and sensitive determination of hypoxic radiosensitizer agent nimorazole
in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.
AB - A highly sensitive, accurate and robust LC-MS/MS method was developed and
validated for determination of nimorazole (NMZ) in rat plasma using metronidazole
(MNZ) as internal standard (IS). The analyte and IS were extracted from plasma by
precipitating protein with acetonitrile and were chromatographed using an Agilent
Poroshell 120, EC-C18 column. The mobile phase was composed of a mixture of
acetonitrile and 0.1 % formic acid (85:15 v/v). The total run time was 1.5 min
and injection volume was 5 MUL. Multiple reaction monitoring mode using the
transitions of m/z 227.1 -> m/z 114.0 for MNZ and m/z 172.10 -> m/z 128.1 for IS
were monitored on a triple quadrupole mass spectrometer, operating in positive
ion mode. The calibration curve was linear in the range of 0.25-200 ng/mL (r(2)
> 0.9996) and the lower limit of quantification was 0.25 ng/mL in the rat plasma
samples. Recoveries of NMZ ranged between 88.05 and 95.25%. The precision (intra
day and inter-day) and accuracy of the quality control samples were 1.25-8.20%
and -2.50-3.10, respectively. The analyte and IS were found to be stable during
all sample storage and analysis procedures. The LC-MS/MS method described here
was validated and successfully applied to pharmacokinetic study in rats.
PMID- 25845450
TI - Standard excision and reconstruction as an alternative to MMS for giant basal
cell carcinoma?
PMID- 25845451
TI - Celebrating the 70(th) birthday of Valery V. Tuchin.
PMID- 25845461
TI - Large optical nonlinearity induced by singlet fission in pentacene films.
AB - By creating two triplet excitons from one photo-excited singlet exciton, singlet
fission in organic semiconductors has drawn tremendous attention for its
potential applications in boosting the efficiency of solar conversion. Here, we
show that this carrier-multiplication effect can also be used to dramatically
improve the nonlinear optical response in organic materials. We have observed
large optical nonlinearity with a magnitude of chi((3)) up to 10(-9) esu in
pentacene films, which is further shown to be a result of singlet fission by
monitoring the temporal dynamics. The potential application of such efficient
nonlinear optical response has been demonstrated with a singlet-fission-induced
polarization rotation.
PMID- 25845462
TI - Modeling and evaluating evidence-based continuing education program in nursing
home dementia care (MEDCED)--training of care home staff to reduce use of
restraint in care home residents with dementia. A cluster randomized controlled
trial.
AB - OBJECTIVE: The aim of this study was to evaluate the effectiveness of a tailored
7-month training intervention "Trust Before Restraint," in reducing use of
restraint, agitation, and antipsychotic medications in care home residents with
dementia. METHODS: This is a single-blind cluster randomized controlled trial in
24 care homes within the Western Norway Regional Health Authority 2011-2013.
RESULTS: From 24 care homes, 274 residents were included in the study, with 118
in the intervention group and 156 in the control group. Use of restraint was
significantly reduced in both the intervention group and the control group
despite unexpected low baseline, with a tendency to a greater reduction in the
control group. There was a significant reduction in Cohen-Mansfield Agitation
Inventory score in both the intervention group and the follow-up group with a
slightly higher reduction in the control group, although this did not reach
significance and a small nonsignificant increase in use of antipsychotics (14.1
17.7%) and antidepressants (35.9-38.4%) in both groups. CONCLUSIONS: This study
reports on the statistically significant reduction in use of restraint in care
homes, both prior and during the 7-month intervention periods, in both
intervention and control groups. When interpreted within the context of the
current climate of educational initiatives to reduce restraint and a greater
focus on the importance of person-centered care, the study also highlights the
potential success achieved with national training programs for care staff and
should be further evaluated to inform future training initiatives both in Norway
and internationally.
PMID- 25845463
TI - Determination of zearalenone in maize products by vortex-assisted ionic-liquid
based dispersive liquid-liquid microextraction with high-performance liquid
chromatography.
AB - A novel method has been developed for the analysis of zearalenone in maize
products by vortex-assisted ionic-liquid-based dispersive liquid-liquid
microextraction combined with HPLC and fluorescence detection. Maize samples were
extracted with methanol/water (80:20, v/v) and the extraction solution was then
used as the dispersive solvent in the microextraction procedure. The analyte was
rapidly transmitted to a small volume of ionic liquid and was determined by HPLC.
Various parameters affecting the recovery of the mycotoxin were investigated,
such as the type and volume of the extraction solvent, the type and volume of the
dispersive solvent, the pH of the aqueous phase, the salt addition, and the time
of vortex and centrifugation. Under the optimal experimental conditions, a good
linearity of the analyte was obtained in the range of 1.0-1000.0 MUg/L with the
correlation coefficient of 0.9998. The limit of detection (S/N = 3) and
quantification (S/N = 10) were 0.3 and 1.0 MUg/kg, and the mean recoveries ranged
from 83.5 to 94.9%, with a relative standard deviation less than 5.0%. The
proposed method was demonstrated to be simple, cheap, quick, and highly selective
and was successfully applied to the determination of zearalenone in maize
products.
PMID- 25845464
TI - Telbivudine in liver transplant recipients: Renal protection does not overcome
the risk of polyneuropathy and myopathy.
AB - The recently reported benefit of telbivudine for renal function has not been
systematically studied in long-term liver transplantation (LT) recipients who are
at high risk for renal impairment. We aimed to examine whether switching
lamivudine therapy to telbivudine could improve renal function in LT recipients
who have impaired renal function. This single-center, prospective cohort study
enrolled LT recipients who were on lamivudine for hepatitis B virus (HBV)
prophylaxis and who had renal impairment for at least 1 year. Lamivudine was
switched to telbivudine. The primary outcome was to evaluate the change in renal
function at weeks 12, 24, 36, and 48. The secondary outcomes were to assess the
efficacy of telbivudine for HBV prophylaxis and the safety profile of telbivudine
in the posttransplant setting. After 45 patients were enrolled, the study was
terminated early because of increased rates of polyneuropathy/myopathy. During
telbivudine treatment (median, 64 weeks), estimated glomerular filtration rate
(eGFR) increased in 34 patients (76%). The improvement in renal function was
prominent after 24 weeks of telbivudine treatment. Telbivudine was effective as
prophylaxis against HBV recurrence. Twenty-six patients (58%) developed
polyneuropathy and/or myopathy. The 1-year estimated incidence of
polyneuropathy/myopathy was 28%. Diabetes was the strongest predictor of
polyneuropathy/myopathy (hazard ratio, 4.13; 95% confidence interval, 1.49-11.50;
P = 0.007). In conclusion, although it seems to have a favorable effect in the
improvement of renal function and seems to be effective in the prevention of HBV
recurrence, the high risk of polyneuropathy and myopathy hampers the use of
telbivudine in LT recipients.
PMID- 25845465
TI - Quantitative single-cell motility analysis of platelet-rich plasma-treated
endothelial cells in vitro.
AB - Platelet-rich plasma (PRP) has been widely applied in regenerative therapy due to
its high concentration of growth factors. Previous in vitro and in vivo studies
have provided evidence supporting the angiogenic activity of PRP. To more
directly demonstrate how PRP acts on endothelial cells, we examined the PRP
induced changes in the motility of human umbilical vein endothelial cells by
examining the involvement of VEGF. Time-lapse quantitative imaging demonstrated
that in the initial phase (~2 h) of treatment, PRP substantially stimulated cell
migration in a wound-healing assay. However, this effect of PRP was not sustained
at significant levels beyond the initial phase. The average net distance of cell
migration at 10 h was 0.45 +/- 0.16 mm and 0.82 +/- 0.23 mm in control and PRP
stimulated cells, respectively. This effect was also demonstrated with
recombinant human VEGF and was significantly attenuated by a neutralizing anti
VEGF antibody. Immunofluorescent examination of paxillin and actin fibers
demonstrated that PRP concomitantly up-regulated focal adhesion and cytoskeletal
formation. Western blotting analysis of phosphorylated VEGFR2 demonstrated that
PRP mainly stimulated the phosphorylation of immature VEGFR2 in a dose- and time
dependent manner, an action that was completely blocked by the neutralizing
antibody. Taken together, these data suggest that PRP acts directly on
endothelial cells via the activation of VEGFR2 to transiently up-regulate their
motility. Thus, the possibility that PRP desensitizes target endothelial cells
for a relatively long period of time after short-term activation should be
considered when the controlled release system of PRP components is designed.
PMID- 25845466
TI - The relationship between fear and pain levels during needle procedures in
children from the parents' perspective.
AB - BACKGROUND: The primary objective was to determine the levels of and potential
relationships between procedure-related fear and pain in children. Secondary
objectives were to determine if there are associations between the child's age
and sex, diagnostic group, time since diagnosis, time since last needle
insertion, cortisol levels and the parent's fear level in relation to fear and
pain. METHODS: The child's level of pain and fear was reported by parents on 0
100 mm visual analogue scales (VAS). One hundred and fifty-one children were
included consecutively when undergoing routine needle insertion into a
subcutaneously implanted intravenous port. All children were subjected to one
needle insertion following topical anaesthesia (EMLA) application. The effect of
the child's age and sex, diagnostic group, time since diagnosis, time since last
needle insertion, cortisol change levels and the parent's fear level, on fear and
pain levels was investigated with multiple regression analysis. RESULTS: The
needle-related fear level (VAS mean 28 mm) was higher than the needle-related
pain level (VAS mean 17 mm) when topical anaesthesia is used according to
parents' reports (n = 151, p < 0.001). With fear as the dependent variable, age
and pain were significantly associated and explained 33% of the variance, and
with pain as the dependent variable, fear, parents' fear and change in cortisol
level were significantly associated and explained 38% of the variance.
CONCLUSIONS: According to parents, children experienced more fear than pain
during needle insertion when topical anaesthesia is used. Therefore, in addition
to pain management, an extended focus on fear-reducing interventions is suggested
for needle procedures.
PMID- 25845467
TI - Prospective quality-of-life outcomes for low-risk prostate cancer: Active
surveillance versus radical prostatectomy.
AB - BACKGROUND: For patients with low-risk prostate cancer (PCa), active surveillance
(AS) may produce oncologic outcomes comparable to those achieved with radical
prostatectomy (RP). Health-related quality-of-life (HRQoL) outcomes are important
to consider, yet few studies have examined HRQoL among patients with PCa who were
managed with AS. In this study, the authors compared longitudinal HRQoL in a
prospective, racially diverse, and contemporary cohort of patients who underwent
RP or AS for low-risk PCa. METHODS: Beginning in 2007, HRQoL data from validated
questionnaires (the Expanded Prostate Cancer Index Composite and the 36-item RAND
Medical Outcomes Study short-form survey) were collected by the Center for
Prostate Disease Research in a multicenter national database. Patients aged <=75
years who were diagnosed with low-risk PCa and elected RP or AS for initial
disease management were followed for 3 years. Mean scores were estimated using
generalized estimating equations adjusting for baseline HRQoL, demographic
characteristics, and clinical patient characteristics. RESULTS: Of the patients
with low-risk PCa, 228 underwent RP, and 77 underwent AS. Multivariable analysis
revealed that patients in the RP group had significantly worse sexual function,
sexual bother, and urinary function at all time points compared with patients in
the AS group. Differences in mental health between groups were below the
threshold for clinical significance at 1 year. CONCLUSIONS: In this study, no
differences in mental health outcomes were observed, but urinary and sexual HRQoL
were worse for patients who underwent RP compared with those who underwent AS for
up to 3 years. These data offer support for the management of low-risk PCa with
AS as a means for postponing the morbidity associated with RP without concomitant
declines in mental health.
PMID- 25845468
TI - Multisite evaluations of a T2 -relaxation-under-spin-tagging (TRUST) MRI
technique to measure brain oxygenation.
AB - PURPOSE: Venous oxygenation (Yv ) is an important index of brain physiology and
may be indicative of brain diseases. A T2 -relaxation-under-spin-tagging (TRUST)
MRI technique was recently developed to measure Yv . A multisite evaluation of
this technique would be an important step toward broader availability and
potential clinical utilizations of Yv measures. METHODS: TRUST MRI was performed
on a total of 250 healthy subjects, 125 from the developer's site and 25 each
from five other sites. All sites were equipped with a 3 Tesla (T) MRI of the same
vendor. The estimated Yv and the standard error (SE) of the estimation epsilonYv
were compared across sites. RESULTS: The averaged Yv and epsilonYv across six
sites were 61.1% +/- 1.4% and 1.3% +/- 0.2%, respectively. Multivariate
regression analysis showed that the estimated Yv was dependent on age (P = 0.009)
but not on performance site. In contrast, the SE of the Yv estimation was site
dependent (P = 0.024) but was less than 1.5%. Further analysis revealed that
epsilonYv was positively associated with the amount of subject motion (P < 0.001)
but negatively associated with blood signal intensity (P < 0.001). CONCLUSION:
This work suggests that TRUST MRI can yield equivalent results of Yv estimation
across different sites.
PMID- 25845469
TI - MED23-associated intellectual disability in a non-consanguineous family.
AB - Intellectual disability (ID) is a heterogeneous condition arising from a variety
of environmental and genetic factors. Among these causes are defects in
transcriptional regulators. Herein, we report on two brothers in a
nonconsanguineous family with novel compound heterozygous, disease-segregating
mutations (NM_015979.3: [3656A > G];[4006C > T], NP_057063.2: [H1219R];[R1336X])
in MED23. This gene encodes a subunit of the Mediator complex that modulates the
expression of RNA polymerase II-dependent genes. These brothers, who had profound
ID, spasticity, congenital heart disease, brain abnormalities, and atypical
electroencephalography, represent the first case of MED23-associated ID in a non
consanguineous family. They also expand upon the clinical features previously
reported for mutations in this gene.
PMID- 25845470
TI - Opioid analgesic prescribing in Australia: a focus on gender and age.
AB - PURPOSE: The use of prescription opioid analgesics has been increasing over the
last few decades in Australia. In particular, oxycodone and fentanyl have
increased substantially. We examined the gender and age trends in the prescribing
of subsidised opioid analgesics in the Australian population for non-palliative
care indications. METHODS: We analysed the Medicare Australia and Drug
Utilisation Sub-Committee databases for prescription data from 2002 to 2009 in 10
year age groups and by gender. Prescriptions were converted to Defined Daily
Doses (DDD)/1000/day using Australian Bureau of Statistics population data.
RESULTS: Overall use increased progressively in 2002-2009 from 12.95 to 16.08
DDD/1000 population/day (average annual increase 3.4%). Codeine was the most
widely used agent followed by tramadol then oxycodone. Dispensed use increased in
those aged in their 20s and 30s to plateau between 30 and 59 years for the three
most preferred analgesics. The peak use of higher dose formulations of oxycodone
was seen in males from 40 years. The highest dose formulation of tramadol was
preferred in those aged up to approximately 70 years. CONCLUSIONS: Reasons for
increased use may include increased prevalence of people with cancer and use for
acute pain. The overall benefit and risk in this escalation of opioid use are
difficult to determine; however, the increasing risk of tolerance, dependence,
overdose and drug diversion suggests to clinicians and policy makers that this
escalation may not be in the best interest of all Australians.
PMID- 25845471
TI - Effect of mineral nutrients on the uptake of Cr(VI) by maize plants.
AB - To determine the potential of maize plants for phytoextraction of chromium (Cr),
and the effect that some mineral nutrients have on this process, the uptake of
this metal was analyzed in vitro. 12-day-old plants were incubated in nutrient
solutions with 200 or 250 MUM potassium chromate and 3mM supplements of nitrate,
phosphate or sulfate. The greatest accumulation of Cr after 48 hours was in
plants that were supplemented with nitrate (800 and 350 mg kg(-1) DW for roots
and stems, respectively) with bioaccumulation factors of 18 and 7 in the roots
and in the foliage, respectively. Moreover, the translocation factor from root to
leaves was 0.4 when nitrate was supplemented; thus, the addition of this nutrient
is recommended when the crop is to be used for phytoextraction of Cr. Considering
the results obtained, the high biomass produced by this crop and the extensive
knowledge of agricultural practices for this plant, we believe that maize has the
potential to be considered in the phytoextraction of Cr, based on preliminary
assays of soil conditions.
PMID- 25845477
TI - No cardiomyopathy in X-linked myopathy with excessive autophagy.
AB - In X-linked myopathy with excessive autophagy (XMEA) progressive sarcoplasmic
accumulation of autolysosomes filled with undegraded debris leads to atrophy and
weakness of skeletal muscles. XMEA is caused by compromised acidification of
lysosomes resulting from hypofunction of the proton pump vacuolar ATPase (V
ATPase), due to hypomorphic mutations in VMA21, whose protein product assembles V
ATPase. To what extent the cardiac muscle is affected is unknown. Therefore we
performed a comprehensive cardiac evaluation in four male XMEA patients, and also
examined pathology of one deceased patient's cardiac and skeletal muscle. None of
the symptomatic men (aged 25-48 years) had history or symptoms of cardiomyopathy.
Resting electrocardiograms and echocardiographies were normal. MRI showed normal
left ventricle ejection fraction and myocardial mass. Myocardial late-gadolinium
enhancement was not detected. The deceased patient's skeletal but not cardiac
muscle showed characteristic accumulation of autophagic vacuoles. In conclusion,
in classic XMEA the myocardium is structurally, electrically and clinically
spared.
PMID- 25845478
TI - Novel PSTPIP1 gene mutation in a patient with pyogenic arthritis, pyoderma
gangrenosum and acne (PAPA) syndrome.
AB - INTRODUCTION: Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome
is a rare autosomal dominant disease that usually presents in childhood with
recurrent sterile arthritis. As the child ages into puberty, cutaneous features
develop and arthritis subsides. We report the case of a now 25-year-old male
patient with PAPA syndrome with the E250K mutation in PSTPIP1. We also present a
systematic literature review of other PAPA cases. METHOD: We conducted a
literature search of PubMed using the following search terms: E250K mutation,
PSTPIP1, and PAPA. RESULTS: PAPA syndrome is caused by mutations on chromosome
15q affecting the proline-serine-threonine phosphatase-interacting protein 1
(PSTPIP1) gene, also known as CD2-binding protein 1 (CD2BP1). The reported cases
of PAPA syndrome currently in the literature involve mutations in A230T and
E250Q. One case of a novel E250K mutation has been reported, which presented with
a different phenotype to previously described cases of PAPA syndrome. CONCLUSION:
With variation present between disease presentations from case to case, it is
possible that the spectrum of PAPA syndrome is wider than currently thought.
Further research is needed which may uncover an as-yet undiscovered genetic
abnormality linking these interrelated diseases together.
PMID- 25845479
TI - Impact of sampling time deviations on the prediction of the area under the curve
using regression limited sampling strategies.
AB - The regression limited sampling strategy approach (R-LSS), which is based on a
small number of blood samples drawn at selected time points, has been used as an
alternative method for the estimation of the area under the concentration-time
curve (AUC). However, deviations from planned sampling times may affect the
performance of R-LSS, influencing related therapeutic decisions and outcomes. The
aim of this study was to investigate the impact of different sampling time
deviation (STD) scenarios on the estimation of AUC by the R-LSS using a
simulation approach. Three types of scenarios were considered going from the
simplest case of fixed deviations, to random deviations and then to a more
realistic case where deviations of mixed nature can occur. In addition, the
sensitivity of the R-LSS to STD in each involved sampling point was evaluated. A
significant impact of STD on the performance of R-LSS was demonstrated. The
tolerance of R-LSS to STD was found to depend not only on the number of sampling
points but more importantly on the duration of the sampling process. Sensitivity
analysis showed that sampling points at which rapid concentration changes occur
were relatively more critical for AUC prediction by R-LSS. As a practical
approach, nomograms were proposed, where the expected predictive performance of R
LSS was provided as a function of STD information. The investigation of STD
impact on the predictive performance of R-LSS is a critical element and should be
routinely performed to guide R-LSS selection and use.
PMID- 25845480
TI - Effect of planar microelectrode geometry on neuron stimulation: finite element
modeling and experimental validation of the efficient electrode shape.
AB - BACKGROUND: Microelectrode arrays have been used successfully for neuronal
stimulation both in vivo and in vitro. However, in most instances currents
required to activate the neurons have been in un-physiological ranges resulting
in neuronal damage and cell death. There is a need to develop electrodes which
require less stimulation current for neuronal activation with physiologically
relevant efficacy and frequencies. NEW METHOD: The objective of the present study
was to examine and compare the stimulation efficiency of different electrode
geometries at the resolution of a single neuron. We hypothesized that increasing
the electrode perimeter will increase the maximum current density at the edges
and enhance stimulation efficiency. To test this postulate, the neuronal
stimulation efficacy of common circular electrodes (smallest perimeter) was
compared with star (medium perimeter), and spiral (largest perimeter with
internal boundaries) electrodes. We explored and compared using both a finite
element model and in vitro stimulation of neurons isolated from Lymnaea central
ganglia. RESULTS: Interestingly, both the computational model and the live
neuronal stimulation experiments demonstrated that the common circular
microelectrode requires less stimulus to activate a cell compared to the other
two electrode shapes with the same surface area. Our data further revealed that
circular electrodes exhibit the largest sealing resistance, stimulus transfer,
and average current density among the three types of electrodes tested.
COMPARISON WITH EXISTING METHODS: Average current density and not the maximum
current density at the edges plays an important role in determining the electrode
stimulation efficiency. CONCLUSION: Circular shaped electrodes are more efficient
in inducing a change in neuronal membrane potential.
PMID- 25845481
TI - Motor imagery classification via combinatory decomposition of ERP and ERSP using
sparse nonnegative matrix factorization.
AB - BACKGROUND: Brain activities could be measured by devices like EEG, MEG, MRI etc.
in terms of electric or magnetic signal, which could provide information from
three domains, i.e., time, frequency and space. Combinatory analysis of these
features could definitely help to improve the classification performance on brain
activities. NMF (nonnegative matrix factorization) has been widely applied in
pattern extraction tasks (e.g., face recognition, gene data analysis) which could
provide physically meaningful explanation of the data. However, brain signals
also take negative values, so only spectral feature has been employed in existing
NMF studies for brain computer interface. In addition, sparsity is an intrinsic
characteristic of electric signals. NEW METHOD: To incorporate sparsity
constraint and enable analysis of time domain feature using NMF, a new solution
for motor imagery classification is developed, which combinatorially analyzes the
ERP (event related potential, time domain) and ERSP (event related spectral
perturbation, frequency domain) features via a modified mixed alternating least
square based NMF method (MALS-NMF for short). RESULTS: Extensive experiments have
verified the effectivity the proposed method. The results also showed that
imposing sparsity constraint on the coefficient matrix in ERP factorization and
basis matrix in ERSP factorization could better improve the algorithm
performance. COMPARISON WITH EXISTING METHODS: Comparisons with other eight
representative methods have further verified the superiority of the proposed
method. CONCLUSIONS: The MALS-NMF method is an effective solution for motor
imagery classification and has shed some new light into the field of brain
dynamics pattern analysis.
PMID- 25845482
TI - Non-invasive mapping of bilateral motor speech areas using navigated transcranial
magnetic stimulation and functional magnetic resonance imaging.
AB - BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a modern
precise method to activate and study cortical functions noninvasively. We
hypothesized that a combination of nTMS and functional magnetic resonance imaging
(fMRI) could clarify the localization of functional areas involved with motor
control and production of speech. NEW METHOD: Navigated repetitive TMS (rTMS)
with short bursts was used to map speech areas on both hemispheres by inducing
speech disruption during number recitation tasks in healthy volunteers. Two
experienced video reviewers, blinded to the stimulated area, graded each trial
offline according to possible speech disruption. The locations of speech
disrupting nTMS trials were overlaid with fMRI activations of word generation
task. RESULTS: COMPARISON WITH EXISTING METHODS: Speech disruptions were
produced on both hemispheres by nTMS, though there were more disruptive
stimulation sites on the left hemisphere. Grade of the disruptions varied from
subjective sensation to mild objectively recognizable disruption up to total
speech arrest. The distribution of locations in which speech disruptions could be
elicited varied among individuals. On the left hemisphere the locations of
disturbing rTMS bursts with reviewers' verification followed the areas of fMRI
activation. Similar pattern was not observed on the right hemisphere.
CONCLUSIONS: The reviewer-verified speech disruptions induced by nTMS provided
clinically relevant information, and fMRI might explain further the function of
the cortical area. nTMS and fMRI complement each other, and their combination
should be advocated when assessing individual localization of speech network.
PMID- 25845483
TI - Bioaerosol emissions from open microalgal processes and their potential
environmental impacts: what can be learned from natural and anthropogenic aquatic
environments?
AB - Open processes for microalgae mass cultivation and/or wastewater treatment
present an air-water interface. Similarly to other open air-aquatic environments,
they are subject to contamination, but as such, they also represent a source of
bioaerosols. Indeed, meteorological, physico-chemical and biological factors
cause aerial dispersion of the planktonic community. Operating conditions like
liquid mixing or gas injection tend to both enhance microbial activity, as well
as intensify aerosolization. Bacteria, virus particles, fungi and protozoa, in
addition to microalgae, are all transient or permanent members of the planktonic
community and can thus be emitted as aerosols. If they should remain viable,
subsequent deposition on various habitats could instigate their colonization of
other environments and the potential expression of their ecological function.
PMID- 25845484
TI - Transcriptional dynamics of Phytophthora infestans during sequential stages of
hemibiotrophic infection of tomato.
AB - Hemibiotrophic plant pathogens, such as the oomycete Phytophthora infestans,
employ a biphasic infection strategy, initially behaving as biotrophs, where
minimal symptoms are exhibited by the plant, and subsequently as necrotrophs,
feeding on dead plant tissue. The regulation of this transition and the breadth
of molecular mechanisms that modulate plant defences are not well understood,
although effector proteins secreted by the pathogen are thought to play a key
role. We examined the transcriptional dynamics of P. infestans in a compatible
interaction with its host tomato (Solanum lycopersicum) at three infection
stages: biotrophy; the transition from biotrophy to necrotrophy; and necrotrophy.
The expression data suggest a tight temporal regulation of many pathways
associated with the suppression of plant defence mechanisms and pathogenicity,
including the induction of putative cytoplasmic and apoplastic effectors. Twelve
of these were experimentally evaluated to determine their ability to suppress
necrosis caused by the P. infestans necrosis-inducing protein PiNPP1.1 in
Nicotiana benthamiana. Four effectors suppressed necrosis, suggesting that they
might prolong the biotrophic phase. This study suggests that a complex regulation
of effector expression modulates the outcome of the interaction.
PMID- 25845485
TI - Ethical issues raised by a ban on the sale of electronic nicotine devices.
AB - BACKGROUND: Some countries have banned the sale of electronic nicotine delivery
systems (ENDS). AIMS: We analyse the ethical issues raised by this ban and
various ways in which the sale of ENDS could be permitted. METHOD: We examine the
ban and alternative policies in terms of the degree to which they respect ethical
principles of autonomy, beneficence, non-maleficence and justice, as follows.
RESULTS: Respect for autonomy: prohibiting ENDS infringes on smokers' autonomy to
use a less harmful nicotine product while inconsistently allowing individuals to
begin and continue smoking cigarettes. Non-maleficence: prohibition is supposed
to prevent ENDS recruiting new smokers and discouraging smokers from quitting,
but it has not prevented uptake of ENDS. It also perpetuates harm by preventing
addicted smokers from using a less harmful nicotine product. Beneficence: ENDS
could benefit addicted smokers by reducing their health risks if they use them to
quit and do not engage in dual use. Distributive justice: lack of access to ENDS
disadvantages smokers who want to reduce their health risks. Different national
policies create inequalities in the availability of products to smokers
internationally. CONCLUSIONS: We do not have to choose between a ban and an
unregulated free market. We can ethically allow ENDS to be sold in ways that
allow smokers to reduce the harms of smoking while minimizing the risks of
deterring quitting and increasing smoking among youth.
PMID- 25845486
TI - Babies born before arrival to hospital and maternity unit closures in Queensland
and Australia.
AB - BACKGROUND: Evidence suggests the closure of maternity units is associated with
an increase in babies born before arrival (BBA). AIM: To explore the association
between the number of maternity units in Australia and Queensland by birthing
numbers, BBA rate and geographic remoteness of the health district where the
mother lives. METHODS: A retrospective study utilised routinely collected
perinatal data (1992-2011). Pearson correlation tested the relationship between
BBA rate and number of maternity units. Linear regression examined this
association over time. FINDINGS: During 1992-2011, the absolute numbers
(N=22,814) of women having a BBA each year in Australia increased by 47% (N=836
1233); and 206% (n=140-429) in Queensland. This coincided with a 41% reduction in
maternity units in Australia (N=623-368=18 per year) and a 28% reduction in
Queensland (n=129-93). BBA rates increased significantly across Australia,
r=0.837, n=20 years, p<0.001 and Queensland, r=0.917, n=20 years, p<0.001 and
this was negatively correlated with the number of maternity units in Australia,
r=-0.804, n=19 years, p<0.001 and Queensland, r=-0.906, n=19 years, p<0.001.
CONCLUSIONS: The closure of maternity units over a 20-year period across
Australia and Queensland is significantly associated with increased BBA rates.
The distribution is not limited to rural and remote areas. Given the high risk of
adverse maternal and neonatal outcomes associated with BBA, it is time to revisit
the closure of units.
PMID- 25845487
TI - Topical treatment with pterostilbene, a natural phytoalexin, effectively protects
hairless mice against UVB radiation-induced skin damage and carcinogenesis.
AB - The aim of our study was to investigate in the SKH-1 hairless mouse model the
effect of pterostilbene (Pter), a natural dimethoxy analog of resveratrol (Resv),
against procarcinogenic ultraviolet B radiation (UVB)-induced skin damage. Pter
prevented acute UVB (360 mJ/cm(2))-induced increase in skin fold, thickness, and
redness, as well as photoaging-associated skin wrinkling and hyperplasia. Pter,
but not Resv, effectively prevented chronic UVB (180 mJ/cm(2), three doses/week
for 6 months)-induced skin carcinogenesis (90% of Pter-treated mice did not
develop skin carcinomas, whereas a large number of tumors were observed in all
controls). This anticarcinogenic effect was associated with (a) maintenance of
skin antioxidant defenses (i.e., glutathione (GSH) levels, catalase, superoxide,
and GSH peroxidase activities) close to control values (untreated mice) and (b)
an inhibition of UVB-induced oxidative damage (using as biomarkers 8-hydroxy-2'
deoxyguanosine, protein carbonyls, and isoprostanes). The molecular mechanism
underlying the photoprotective effect elicited by Pter was further evaluated
using HaCaT immortalized human keratinocytes and was shown to involve potential
modulation of the Nrf2-dependent antioxidant response.
PMID- 25845488
TI - Analysis of quality improvement efforts in preventing glucocorticoid-induced
osteoporosis.
AB - OBJECTIVE: To report and analyze quality improvement (QI) efforts that are aimed
at increasing adherence to preventive guidelines for glucocorticoid-induced
osteoporosis (GIOP). METHODS: We performed a PubMed literature search for full
length articles in English between 1966 and 2013, describing approaches for
improving the quality of GIOP care. We reviewed articles using a structured
approach and abstracted information on the patient population, study design, QI
intervention, and primary outcome measures. A descriptive analysis was then
performed. RESULTS: Literature search identified 661 articles; 38 were screened
by abstract, 10 were identified for full review, and 7 were included. Two non
randomized, uncontrolled studies of system changes showed significant
improvements in GIOP prevention: one increased concomitant prescriptions of
glucocorticoids and calcium (37-49%, p < 0.0001) and vitamin D (38-53%, p <
0.0001) using a computerized order entry system; another used a dedicated
clinical team to increase vitamin D levels from 19.5 to 29.4 (p = 0.001) and
improve GIOP-related habits. Five articles described education-based
interventions, including 3 randomized controlled trials (RCTs). Two non
significant RCTs focused on physicians, but one directed towards pharmacists and
patients did increase calcium supplementation in the intervention vs. control arm
(55.7% vs. 31.6%, p < 0.05). Two other non-randomized educational interventions
did not show benefits. Comparison of articles was limited by the heterogeneity of
the intervention methods and outcome measures used. CONCLUSION: None of the
interventions produced robust changes, with overall adherence to GIOP guidelines
remaining low. System-based interventions appeared more effective than education
based interventions, but a diverse array of factors likely needs to be addressed,
requiring more randomized controlled trials and greater standardization of
outcome measures.
PMID- 25845489
TI - Antithrombotic therapy for left ventricular assist devices in adults: a
systematic review.
AB - BACKGROUND: Left ventricular assist devices (LVADs) have dramatically increased
the survival of adults with end-stage systolic heart failure. However, rates of
bleeding and thromboembolism remain high. OBJECTIVES: We completed a systematic
review to evaluate outcomes of adults with LVADs treated with various
anticoagulant and antiplatelet strategies. METHODS: Databases were searched using
the terms 'assist device', 'thrombosis', and 'anticoagulant' or 'platelet
aggregation inhibitor' with appropriate synonyms, device names and manufacturers.
RESULTS AND CONCLUSIONS: Of 977 manuscripts, 24 articles met the inclusion
criteria of adults with implanted LVADs where clinical outcomes were defined
based on anticoagulant and/or antiplatelet regimen. Most studies reported
treatment with unfractionated heparin post-operatively which was transitioned to
a vitamin K antagonist (VKA). Goal INR varied between 1.5-3.5. Antiplatelet
regimens ranged from no treatment to dual therapy. Definition of major bleeding
differed between trials and incidence varied between 0% and 58%. The available
evidence could not demonstrate a clear benefit of aspirin compared with VKA
therapy alone [stroke RR 1.02 (95% CI 0.49-2.1)]. There was a suggestion that
treatment with aspirin and dipyridamole decreased the risk of thromboembolism
compared to aspirin [RR 0.50 (0.36-0.68)], but the comparison is limited by
differences in demographics, devices, and INR goals among studies. Additionally,
most studies did not blind investigators to outcomes thus contributing to an
increased risk for bias. Clinical equipoise exists as to the most appropriate
antithrombotic therapy in LVAD patients. Randomization between regimens within a
prospective trial is needed to define the treatment regimen that minimizes both
bleeding and thrombotic complications.
PMID- 25845491
TI - Immunoglobulin A in serum: an old acquaintance as a new prognostic biomarker in
idiopathic pulmonary fibrosis.
AB - Immunoglobulin (Ig)A is an important immunoglobulin in mucosal immunity and
protects the lungs against invading pathogens. The production of IgA is regulated
by transforming growth factor (TGF)-beta, a versatile cytokine and key player in
the pathogenesis of pulmonary fibrosis. TGF-beta is up-regulated in patients with
idiopathic pulmonary fibrosis (IPF), but difficult to use as a biomarker. The aim
of this study was to evaluate the prognostic value of IgA in serum in patients
with IPF. We examined IgA levels at time of diagnosis in 86 patients diagnosed
with IPF. Mean serum IgA level in IPF is 3.22 g/l and regression analyses showed
a significant association with mortality (hazard ratio = 1.445, P = 0.002). A
significantly worse survival was found in patients with IgA serum levels > 2.85
g/l compared to patients with lower IgA serum levels (P = 0.003). These findings
were confirmed in a duplication cohort. In conclusion, the level of IgA in blood
is a promising prognostic marker in IPF and can be implemented easily in the
hospital setting. Future studies are warranted to investigate if repeated
measurements of serum IgA can further improve the performance of serum IgA as a
prognostic marker.
PMID- 25845492
TI - Parental reporting of response to oral cannabis extracts for treatment of
refractory epilepsy.
AB - OBJECTIVE: Oral cannabis extracts (OCEs) have been used in the treatment of
epilepsy; however, no studies demonstrate clear efficacy. We report on a cohort
of pediatric patients with epilepsy who were given OCE and followed in a single
tertiary epilepsy center. METHODS: A retrospective chart review of children and
adolescents who were given OCE for treatment of their epilepsy was performed.
RESULTS: Seventy-five patients were identified of which 57% reported any
improvement in seizure control and 33% reported a >50% reduction in seizures
(responders). If the family had moved to CO for OCE treatment, the responder rate
was 47% vs. 22% for children who already were in CO. The responder rate varied
based on epilepsy syndrome: Dravet 23%, Doose 0%, and Lennox-Gastaut syndrome
(LGS) 88.9%. The background EEG of the 8 responders where EEG data were available
was not improved. Additional benefits reported included: improved
behavior/alertness (33%), improved language (10%), and improved motor skills
(10%). Adverse events (AEs) occurred in 44% of patients including increased
seizures (13%) and somnolence/fatigue (12%). Rare adverse events included
developmental regression, abnormal movements, status epilepticus requiring
intubation, and death. SIGNIFICANCE: Our retrospective study of OCE use in
pediatric patients with epilepsy demonstrates that some families reported patient
improvement with treatment; however, we also found a variety of challenges and
possible confounding factors in studying OCE retrospectively in an open-labeled
fashion. We strongly support the need for controlled, blinded studies to evaluate
the efficacy and safety of OCE for treatment of pediatric epilepsies using
accurate seizure counts, formal neurocognitive assessments, as well as EEG as a
biomarker. This study provides Class III evidence that OCE is well tolerated by
children and adolescents with epilepsy.
PMID- 25845493
TI - Cross-species pharmacological characterization of the allylglycine seizure model
in mice and larval zebrafish.
AB - Treatment-resistant seizures affect about a third of patients suffering from
epilepsy. To fulfill the need for new medications targeting treatment-resistant
seizures, a number of rodent models offer the opportunity to assess a variety of
potential treatment approaches. The use of such models, however, has proven to be
time-consuming and labor-intensive. In this study, we performed pharmacological
characterization of the allylglycine (AG) seizure model, a simple in vivo model
for which we demonstrated a high level of treatment resistance. (d,l)
Allylglycine inhibits glutamic acid decarboxylase (GAD) - the key enzyme in gamma
aminobutyric acid (GABA) biosynthesis - leading to GABA depletion, seizures, and
neuronal damage. We performed a side-by-side comparison of mouse and zebrafish
acute AG treatments including biochemical, electrographic, and behavioral
assessments. Interestingly, seizure progression rate and GABA depletion kinetics
were comparable in both species. Five mechanistically diverse antiepileptic drugs
(AEDs) were used. Three out of the five AEDs (levetiracetam, phenytoin, and
topiramate) showed only a limited protective effect (mainly mortality delay) at
doses close to the TD50 (dose inducing motor impairment in 50% of animals) in
mice. The two remaining AEDs (diazepam and sodium valproate) displayed protective
activity against AG-induced seizures. Experiments performed in zebrafish larvae
revealed behavioral AED activity profiles highly analogous to those obtained in
mice. Having demonstrated cross-species similarities and limited efficacy of
tested AEDs, we propose the use of AG in zebrafish as a convenient and high
throughput model of treatment-resistant seizures.
PMID- 25845494
TI - Self-reported aggressiveness during treatment with levetiracetam correlates with
depression.
AB - PURPOSE: The purpose of this study was to identify clinical correlates of self
reported aggressiveness (SRA) in patients with epilepsy treated with
levetiracetam (LEV) with special reference to the role of depression. METHODS: A
consecutive sample of adult outpatients with epilepsy was assessed with the
Neurological Disorder Depression Inventory for Epilepsy, the Adverse Event
Profile (AEP), and the Emotional Thermometer. RESULTS: From a total sample of 163
consecutive patients treated with LEV, SRA at any level (from rarely a problem to
always) was associated with a 7-fold increased risk of being depressed (95% CI:
3.0-17.5; p<0.001). Self-reported aggressiveness was reported as "always" a
problem by 9.8% of the patients. In these patients, apart from depression, SRA
was associated with high AEP total scores (55.1 vs. 39.3; p<0.001) and
polytherapy (43.8% vs. 19.8%; p=0.034). Anxiety scores were not elevated (4.9 vs.
3.6; p=0.183). CONCLUSIONS: Self-reported aggressiveness during treatment with
LEV is not an isolated symptom but is associated with depressed mood. Anxiety
mediated mechanisms do not seem to be involved.
PMID- 25845496
TI - 3,4-Dihydroxyphenylacetic acid, a microbiota-derived metabolite of quercetin,
protects against pancreatic beta-cells dysfunction induced by high cholesterol.
AB - Cholesterol plays an important role in inducing pancreatic beta-cell dysfunction,
characterized by an impaired insulin secretory response to glucose, representing
a hallmark of the transition from pre-diabetes to diabetes. 3,4
dihydroxyphenylacetic acid (ES) is a scarcely studied microbiota-derived
metabolite of quercetin with antioxidant properties. The aim of this study was to
determine the protective effect of ES against apoptosis, mitochondrial
dysfunction and oxidative stress induced by cholesterol in Min6 pancreatic beta
cells. Cholesterol decreased viability, induced apoptosis and mitochondrial
dysfunction by reducing complex I activity, mitochondrial membrane potential, ATP
levels and oxygen consumption. Cholesterol promoted oxidative stress by
increasing cellular and mitochondrial reactive oxygen species and lipid
peroxidation and decreasing antioxidant enzyme activities; in addition, it
slightly increased Nrf2 translocation to the nucleus. These events resulted in
the impairment of the glucose-induced insulin secretion. ES increased Nrf2
translocation to the nucleus and protected pancreatic beta-cells against impaired
insulin secretion induced by cholesterol by preventing oxidative stress,
apoptosis and mitochondrial dysfunction. Nrf2 activation seems to be involved in
the mechanisms underlying the antioxidant protection exerted by ES in addition to
preventing the disruption of antioxidant enzymatic defenses. Although additional
in vivo experiments are required, this metabolite is suggested as a promising
drug target for the prevention of the pathological development from a pre
diabetic to a diabetic state.
PMID- 25845495
TI - Risk stratification with cervical length and fetal fibronectin in women with
threatened preterm labor before 34 weeks and not delivering within 7 days.
AB - OBJECTIVE: To stratify the risk of spontaneous preterm delivery using cervical
length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor
who remained pregnant after 7 days. DESIGN: Prospective observational study.
SETTING: Nationwide cohort of women with threatened preterm labor from the
Netherlands. POPULATION: Women with threatened preterm labor between 24 and 34
weeks with a valid CL and fFN measurement and remaining pregnant 7 days after
admission. METHODS: Kaplan-Meier and Cox proportional hazards models were used to
estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery.
MAIN OUTCOME MEASURES: Spontaneous delivery between 7 and 14 days after initial
presentation and spontaneous preterm delivery before 34 weeks. RESULTS: The risk
of delivery between 7 and 14 days was significantly increased for women with a CL
< 15 mm or a CL >=15 to <30 mm and a positive fFN, compared with women with a CL
>=30 mm: HR 22.3 [95% confidence interval (CI) 2.6-191] and 14 (95% CI 1.8-118),
respectively. For spontaneous preterm delivery before 34 weeks the risk was
increased for women with a CL < 15 mm [HR 6.3 (95% CI 2.6-15)] or with a CL >=15
to <30 mm with either positive fFN [HR 3.6 (95% CI 1.5-8.7)] or negative fFN [HR
3.0 (95% CI 1.2-7.1)] compared with women with a CL >= 30 mm. CONCLUSIONS: In
women remaining pregnant 7 days after threatened preterm labor, CL and fFN
results can be used in risk stratification for spontaneous delivery.
PMID- 25845497
TI - Receptor channel TRPC6 orchestrate the activation of human hepatic stellate cell
under hypoxia condition.
AB - Hepatic stellate cells (HSCs), a specialized stromal cytotype have a great impact
on the biological behaviors of liver diseases. Despite this fact, the underlying
mechanism that regulates HSC still remains poorly understood. The aim of the
present study was to understand the role of TRPC6 signaling in regulating the
molecular mechanism of HSCs in response to hypoxia. In the present study we
showed that under hypoxia condition, the upregulated Hypoxia Inducible Factor
1alpha (HIF1alpha) increases NICD activation, which in turn induces the
expression of transient receptor potential channel 6 (TRPC6) in HSC line lx-2.
TRPC6 causes a sustained elevation of intracellular calcium which is coupled with
the activation of the calcineurin-nuclear factor of activated T-cell (NFAT)
pathway which activates the synthesis of extracellular matrix proteins. TRPC6
also activates SMAD2/3 dependent TGF-beta signaling in facilitating upregulated
expression of alphaSMA and collagen. As activated HSCs may be a suitable target
for HCC therapy and targeting these cells rather than the HCC cells may result in
a greater response. Collectively, our studies indicate for the first time the
detailed mechanism of activation of HSC through TRPC6 signaling and thus being a
promising therapeutic target.
PMID- 25845498
TI - GPR4 decreases B16F10 melanoma cell spreading and regulates focal adhesion
dynamics through the G13/Rho signaling pathway.
AB - The effect of acidosis, a biochemical hallmark of the tumor microenvironment, on
cancer progression and metastasis is complex. Both pro- and anti-tumorigenic
effects of acidosis have been reported and the acidic microenvironment has been
exploited for specific delivery of drugs, imaging agents, and genetic constructs
into tumors. In this study we investigate the spreading and focal adhesion of
B16F10 melanoma cells that are genetically engineered to overexpress the pH
sensing G protein-coupled receptor GPR4. By using cell attachment assays we found
that GPR4 overexpression delayed cell spreading and altered the spatial
localization of dynamic focal adhesion complex, such as the localization of
phosphorylated focal adhesion kinase (FAK) and paxillin, at acidic pH. The
potential G-protein and downstream signaling pathways that are responsible for
these effects were also investigated. By using the Rho inhibitor CT04 (C3
transferase), the Rho-associated kinase (ROCK) inhibitors Y27632 and thiazovivin,
the myosin light chain kinase (MLCK) inhibitor staurosporine or a G12/13
inhibitory construct, cell spreading was restored whereas the inhibition and
activation of the Gq and Gs pathways had little or no effect. Altogether our
results indicate that through the G12/13/Rho signaling pathway GPR4 modulates
focal adhesion dynamics and reduces cell spreading and membrane ruffling.
PMID- 25845499
TI - Preservation of high glycolytic phenotype by establishing new acute lymphoblastic
leukemia cell lines at physiologic oxygen concentration.
AB - Cancer cells typically exhibit increased glycolysis and decreased mitochondrial
oxidative phosphorylation, and they continue to exhibit some elevation in
glycolysis even under aerobic conditions. However, it is unclear whether cancer
cell lines employ a high level of glycolysis comparable to that of the original
cancers from which they were derived, even if their culture conditions are
changed to physiologically relevant oxygen concentrations. From three childhood
acute lymphoblastic leukemia (ALL) patients we established three new pairs of
cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%)
oxygen concentrations. Cell lines established in 20% oxygen exhibited lower
proliferation, survival, expression of glycolysis genes, glucose consumption, and
lactate production. Interestingly, the effects of oxygen concentration used
during cell line initiation were only partially reversible when established cell
cultures were switched from one oxygen concentration to another for eight weeks.
These observations indicate that ALL cell lines established at atmospheric oxygen
concentration can exhibit relatively low levels of glycolysis and these levels
are semi-permanent, suggesting that physiologic oxygen concentrations may be
needed from the time of cell line initiation to preserve the high level of
glycolysis commonly exhibited by leukemias in vivo.
PMID- 25845500
TI - Identification and fine mapping of quantitative trait loci for the number of
vascular bundle in maize stem.
AB - Studies that investigated the genetic basis of source and sink related traits
have been widely conducted. However, the vascular system that links source and
sink received much less attention. When maize was domesticated from its wild
ancestor, teosinte, the external morphology has changed dramatically; however,
less is known for the internal anatomy changes. In this study, using a large
maize-teosinte experimental population, we performed a high-resolution
quantitative trait locus (QTL) mapping for the number of vascular bundle in the
uppermost internode of maize stem. The results showed that vascular bundle number
is dominated by a large number of small-effect QTLs, in which a total of 16 QTLs
that jointly accounts for 52.2% of phenotypic variation were detected, with no
single QTL explaining more than 6% of variation. Different from QTLs for typical
domestication traits, QTLs for vascular bundle number might not be under
directional selection following domestication. Using Near Isogenic Lines (NILs)
developed from heterogeneous inbred family (HIF), we further validated the effect
of one QTL qVb9-2 on chromosome 9 and fine mapped the QTL to a 1.8-Mb physical
region. This study provides important insights for the genetic architecture of
vascular bundle number in maize stem and sets basis for cloning of qVb9-2.
PMID- 25845501
TI - Physicochemical control of bacterial and protist community composition and
diversity in Antarctic sea ice.
AB - Due to climate change, sea ice experiences changes in terms of extent and
physical properties. In order to understand how sea ice microbial communities are
affected by changes in physicochemical properties of the ice, we used 454
sequencing of 16S and 18S rRNA genes to examine environmental control of
microbial diversity and composition in Antarctic sea ice. We observed a high
diversity and richness of bacteria, which were strongly negatively correlated
with temperature and positively with brine salinity. We suggest that bacterial
diversity in sea ice is mainly controlled by physicochemical properties of the
ice, such as temperature and salinity, and that sea ice bacterial communities are
sensitive to seasonal and environmental changes. For the first time in Antarctic
interior sea ice, we observed a strong eukaryotic dominance of the dinoflagellate
phylotype SL163A10, comprising 63% of the total sequences. This phylotype is
known to be kleptoplastic and could be a significant primary producer in sea ice.
We conclude that mixotrophic flagellates may play a greater role in the sea ice
microbial ecosystem than previously believed, and not only during the polar night
but also during summer when potential food sources are abundant.
PMID- 25845502
TI - Novel selective inhibitor of Leishmania (Leishmania) amazonensis arginase.
AB - Arginase is a glycosomal enzyme in Leishmania that is involved in polyamine and
trypanothione biosynthesis. The central role of arginase in Leishmania
(Leishmania) amazonensis was demonstrated by the generation of two mutants: one
with an arginase lacking the glycosomal addressing signal and one in which the
arginase-coding gene was knocked out. Both of these mutants exhibited decreased
infectivity. Thus, arginase seems to be a potential drug target for Leishmania
treatment. In an attempt to search for arginase inhibitors, 29 derivatives of the
[1,2,4]triazolo[1,5-a]pyrimidine system were tested against Leishmania
(Leishmania) amazonensis arginase in vitro. The [1,2,4]triazolo[1,5-a]pyrimidine
scaffold containing R1 = CF3 exhibited greater activity against the arginase
rather than when the substituent R1 = CH3 in the 2-position. The novel compound
2-(5-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7
yl)hydrazinecarbothioamide (30) was the most potent, inhibiting arginase by a non
competitive mechanism, with the Ki and IC50 values for arginase inhibition
estimated to be 17 +/- 1 MUm and 16.5 +/- 0.5 MUm, respectively. These results
can guide the development of new drugs against leishmaniasis based on
[1,2,4]triazolo[1,5-a]pyrimidine derivatives targeting the arginase enzyme.
PMID- 25845503
TI - Accuracy of thyroid nodule sonography for the detection of thyroid cancer in
children: systematic review and meta-analysis.
AB - INTRODUCTION: Thyroid ultrasound (US) is a widely used tool for evaluating
thyroid nodules. Various US features have been suggested as predictors of thyroid
cancer in children. OBJECTIVE: To conduct a systematic review and meta-analysis
to assess the diagnostic accuracy of different thyroid US features in detecting
thyroid cancer in children. METHODS: We searched multiple online databases for
cohort studies that enrolled paediatric patients with thyroid nodules (age <21
years) and evaluated the accuracy of 12 relevant ultrasound features. Diagnostic
measures were pooled across studies using a random effects model. RESULTS: The
search strategy yielded 1199 citations, of which 12 studies met the predefined
inclusion criteria (750 nodules). The prevalence of thyroid cancer was 27.2%
(40.8% in patients with a history of radiation exposure and 23.2% in patients
without a history of exposure to radiation). The most common cancer was papillary
thyroid cancer (86.7%). The presence of internal calcifications and enlarged
cervical lymph nodes were the US features with the highest likelihood ratio [4.46
(95% CI: 1.87-10.64) and 4.96 (95% CI: 2.01-12.24), respectively] for thyroid
cancer. A cystic nodule was the feature with highest likelihood ratio for benign
nodules [1.96 (95% CI: 0.87-4.43)]. CONCLUSION: Thyroid US features are not
highly accurate predictors of benign or malignant aetiology of thyroid nodules in
children. Internal calcification may predict malignancy, and cystic appearance
may suggest benign aetiology.
PMID- 25845504
TI - Is methylisothiazolinone contact allergy a risk factor for polysensitization?
PMID- 25845505
TI - Acute kidney injury in severe sepsis: pathophysiology, diagnosis, and treatment
recommendations.
AB - OBJECTIVE: To review the unique pathophysiology of sepsis-induced acute kidney
injury (AKI) and highlight the relevant aspects of the Kidney Disease: Improving
Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury that
may apply to veterinary patients. DATA SOURCES: Electronic search of MEDLINE
database. HUMAN DATA SYNTHESIS: Sepsis-induced AKI is diagnosed in up to 47% of
human ICU patients and is seen as a major public health concern associated with
increased mortality and increased progression to chronic kidney disease (CKD).
Consensus criteria for the definition and classification of AKI has allowed for
accurate description of the epidemiology of patients with AKI. AKI develops from
a complex relationship between the initial insult and activation of inflammation
and coagulation. In contrast to the traditional view, clinical and experimental
data dispute the role of renal ischemia-reperfusion in the development of sepsis
induced AKI. Renal tubular dysfunction with activation of the tubuloglomerular
feedback mechanism appears to be a crucial contributor to sepsis-induced AKI.
Furosemide and n-acetylcysteine (NAC) do not appear to be helpful in the
treatment of AKI. Hydroxyethyl starches (HES), dopamine, and supraphysiological
concentrations of chloride are harmful in patients with AKI. VETERINARY DATA
SYNTHESIS: Community and hospital-acquired AKI is a significant factor affecting
survival in critical ill patients. Sepsis-induced AKI occurs in 12% of dogs with
abdominal sepsis and is an important contributor to mortality. Early detection of
AKI in hospitalized patients currently offers the best opportunity to improve
patient outcome. The use of urinary biomarkers to diagnose early AKI should be
evaluated in critical care patients. CONCLUSION: Veterinary clinical trials
comparing treatment choices with the development of AKI are needed to make
evidence-based recommendations for the prevention and treatment of AKI.
PMID- 25845506
TI - Retrospective evaluation of risk factors and outcome predictors in cats with
diabetic ketoacidosis (1997-2007): 93 cases.
AB - OBJECTIVES: To determine risk factors and outcome predictors in cats with
diabetic ketoacidosis (DKA). DESIGN: Retrospective study. Inclusion in the DKA
group required blood glucose concentration > 13.9 mmol/L (250 mg/dL), venous pH <
7.35, and urine or serum acetoacetate concentration greater than 1.5 mmol/L (15
mg/dL). Signalment and weight were recorded in all cats with uncomplicated
diabetes mellitus (DM) without DKA and in all other nondiabetic cats examined
during the study period. Clinicopathologic variables, concurrent disorders, and
initial insulin intravenous (IV) continuous-rate infusion (CRI) concentration of
1.1 or 2.2 U/kg/240 mL bag of 0.9% NaCl, were examined for a possible association
with outcome. SETTING: University teaching hospital. ANIMALS: Ninety-three cats
with DKA, 682 cats with uncomplicated DM, and 16,926 cats without DM or DKA.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cats with DKA were younger
(median age 9.4 years; range, 1-17.9 years) than cats with uncomplicated DM
(median 11.6 years; range 0.7-19.5 years, P < 0.0003). Siamese cats were
overrepresented in the DKA group compared to the uncomplicated DM or nondiabetic
group (P = 0.038 and P = 0.01, respectively). Poor outcome (defined as death due
to disease or by euthanasia) in 36 cats with DKA (39%) was associated with
increased initial creatinine, BUN, total serum magnesium, and total bilirubin
concentrations (P = 0.007, P = 0.005, P = 0.03, P = 0.03, respectively). Cats
treated with a higher concentration of insulin were less likely to have a poor
outcome compared to cats treated with a lower concentration of insulin (odds
ratio 0.14, 95% confidence interval 0.02-1.16, P = 0.02). CONCLUSIONS: Cats with
DKA are more likely to be Siamese than cats with uncomplicated DM. Poor outcome
of cats with DKA is associated with increased initial creatinine, BUN, total
magnesium, and total bilirubin concentrations. Good outcome was associated with a
higher concentration of IV insulin CRI.
PMID- 25845514
TI - CHILD Syndrome: Successful Treatment of Skin Lesions with Topical
Simvastatin/Cholesterol Ointment--A Case Report.
AB - CHILD syndrome is a rare X-linked dominant condition that presents with
congenital hemidysplasia, Ichthyosiform erythroderma, and limb defects in
affected patients. We report the case of a 10-year-old girl treated with topical
simvastatin and cholesterol ointment, after which her skin lesions significantly
improved within the first 30 days of treatment.
PMID- 25845515
TI - Using discussion groups as a strategy for postgraduate implant dentistry students
to reflect.
AB - INTRODUCTION: More than undergraduates, postgraduate students have the day-to-day
clinical experience to reflect upon. Nevertheless, reflection in postgraduate
dental education is less well studied. Hence, the purpose was to investigate the
attitude towards reflection and the content of reflections in postgraduate
implant dentistry education in the UK and Belgium. MATERIALS AND METHODS: To
investigate the attitude towards reflection, a questionnaire was administered to
the 10 postgraduates at UCL Eastman Dental Institute (EDI) and 6 postgraduates at
Ghent University (UGent). Additionally, students were invited to attend two
reflective sessions (60-90 minutes). The sessions' audio recordings were
transcribed and analysed using a thematic approach. RESULTS: In total, 16
postgraduate implant dentistry students participated. Although the majority
reported prior experience with reflection, there was variation in the provided
definitions of reflection. EDI students agreed with reflection being beneficial
for professional development/clinical reasoning and were positive about
discussing clinical experiences in groups, but were divided about
individual/group reflections. Their UGent counterparts were more indecisive
(=neutral), but were positive about discussing clinical experiences. Thematic
analysis identified recurring themes as individual learning process, learning and
clinical experiences, attitude towards implant dentistry and course programme.
EDI postgraduates' reflections focussed on specific clinical situations, while
UGent postgraduates' reflections described general considerations. CONCLUSION:
Although students/professionals often report to reflect, it is not clear
whether/how they actually reflect, due to the all-purpose word reflection has
become. A strategy, using group discussions along with supervision/guidance in
how to reflect, demonstrated to expand clinical reasoning into reflections about
postgraduate students' clinical actions and professional growth.
PMID- 25845516
TI - Nickel-catalysed P-C bond formation via P-H/C-CN cross coupling reactions.
AB - Nickel-catalysed P-H/C-CN cross coupling reactions take place efficiently under
mild reaction conditions affording the corresponding sp(2)C-P bonds. This
transformation provides a convenient method for the preparation of arylphosphines
and arylphosphine oxides from the readily available P-H compounds and
arylnitriles.
PMID- 25845517
TI - Theoretical study on reaction mechanisms of nitrite reduction by copper nitrite
complexes: toward understanding and controlling possible mechanisms of copper
nitrite reductase.
AB - Using density functional theory, we studied denitrification reaction mechanisms
of copper adducts of tris(pyrazolyl)methane and hydrotris(pyrazolyl)borate models
of a copper nitrite reductase (Cu-NiR), and herein propose several possible
reaction pathways, including some parts that have never been examined previously.
Because electron and proton transfer reactions participate in the enzymatic
cycles of Cu-NiR, the Gibbs energy of a proton in solution, G(H(+)), and the
redox potential, Eredox, of the model Cu-NiR are also evaluated. Although the
pathway where a nitrite is provided as HNO2 is energetically preferable, a well
known reaction pathway passing through the resting state with an active site
occupied by a water molecule where nitrite is provided as NO2(-) is the main
recognized pathway under normal conditions. These features do not change whether
the electron transfer occurs before production of NO or not. However, our results
suggest that the pathway involving HNO2 might become dominant under low pH
conditions in conjunction with experimental results.
PMID- 25845518
TI - Bicarbonate Therapy in End-Stage Renal Disease: Current Practice Trends and
Implications.
AB - Management of metabolic acidosis covers the entire spectrum from oral bicarbonate
therapy and dietary modifications in chronic kidney disease to delivery of high
doses of bicarbonate-based dialysate during maintenance haemodialysis (MHD). Due
to the gradual depletion of the body's buffers and rapid repletion during MHD,
many potential problems arise as a result of our current treatment paradigms.
Several studies have given rise to conflicting data about the adverse effects of
our current practice patterns in MHD. In this review, we will describe the
pathophysiology and consequences of metabolic acidosis and its therapy in CKD and
ESRD, and discuss current evidence supporting a more individualized approach for
bicarbonate therapy in MHD.
PMID- 25845519
TI - A retrospective study of factors which determine a negative blood culture in
Cambodian children diagnosed with enteric fever.
AB - BACKGROUND: Blood cultures are used to confirm a diagnosis of enteric fever but
reported sensitivities can be as low as 40%. AIMS: To determine the factors
associated with a negative blood culture in Cambodian children with suspected
enteric fever. METHODS: In a retrospective study of hospitalised Cambodian
children given a discharge diagnosis of enteric fever, the following factors
associated with a negative blood culture were analysed: age, blood culture
volume, prior antibiotic therapy, duration of illness and disease severity.
RESULTS: In 227 hospitalised Cambodian children with a discharge diagnosis of
enteric fever, it was confirmed in 70% by a positive blood culture. There was no
association between a negative blood culture and younger age, lower blood volumes
for culture, prior antibiotic therapy, a late presentation or milder disease.
CONCLUSIONS: Although blood culture sensitivity was higher than expected,
alternative simple, rapid and sensitive tests are needed for diagnosing enteric
fever.
PMID- 25845520
TI - Chromosome structure deficiencies in MCPH1 syndrome.
AB - Mutations in the MCPH1 gene result in primary microcephaly in combination with a
unique cellular phenotype of defective chromosome condensation. MCPH1 patient
cells display premature chromosome condensation in G2 phase of the cell cycle and
delayed decondensation in early G1 phase, observable as an increased proportion
of cells with prophase-like appearance. MCPH1 deficiency thus appears to uncouple
the chromosome cycle from the coordinated series of events that take place during
mitosis such as some phases of the centrosome cycle and nuclear envelope
breakdown. Here, we provide a further characterization of the effects of MCPH1
loss-of-function on chromosome morphology. In comparison to healthy controls,
chromosomes of MCPH1 patients are shorter and display a pronounced coiling of
their central chromatid axes. In addition, a substantial fraction of metaphase
chromosomes shows apparently unresolved chromatids with twisted appearance. The
patient chromosomes also showed signs of defective centromeric cohesion, which
become more apparent and pronounced after harsh hypotonic conditions. Taking
together, the observed alterations indicate additional so far unknown functions
of MCPH1 during chromosome shaping and dynamics.
PMID- 25845521
TI - An improved isolation technique for shaggy brachiocephalic artery and aortic arch
replacement.
AB - A mobile plaque in the ascending and transverse aorta increases the risk of
cerebral infarction during treatment of an arch aneurysm. A previous report
described an isolation technique for replacing the ascending and transverse aorta
with a mobile atheroma by selective hypothermic antegrade cerebral perfusion
(Shiiya et al., Ann Thorac Surg 72:1401-1402, 2001). Here, we present an improved
isolation technique for more severe conditions, such as shaggy aorta and shaggy
brachiocephalic artery, in two patients. First, we anastomosed both axillae
arteries with grafts and placed drainage cannulae in the superior and inferior
venae cavae prior to filling the cardio-pulmonary bypass system with blood. Next,
we cannulated the right common carotid artery and selective cerebral perfusion
was started prior to cannulation and perfusion of the left common carotid artery.
Systemic perfusion was then initiated through the axillae grafts. Both patients
who underwent this procedure recovered without neurologic complications.
PMID- 25845522
TI - Suicide Ideations, Suicide Attempts, and Completed Suicide in Persons with
Pathological Gambling and Their First-Degree Relatives.
AB - We examined the relationship between suicidal ideations and attempts in 95
probands with pathological gambling (PG), 91 controls, and 1075 first-degree
relatives. The results were analyzed using logistic regression with generalized
estimating equations. Thirty-four PG probands (35.8%) and 4 controls (4.4%) had
attempted suicide (OR = 12.12, p < .001); in 13 probands, the attempt occurred
before PG onset. Lifetime suicidal ideations occurred in 60 PG probands (63.2%)
and 12 controls (13.2%) (OR = 11.29, p < .001). Suicidality in PG probands is a
marker of PG severity and is associated with greater psychiatric comorbidity.
Offspring of PG probands had significantly higher rates of suicide attempts than
control offspring.
PMID- 25845524
TI - Craniofacial asymmetry in non-syndromic orthodontic subjects: clinical and
postural evaluation.
AB - OBJECTIVE: The aim of this study was to evaluate the possible influence of a
malocclusion pattern on a patient's posture. METHODS: Patients affected by
symmetric malocclusion or malocclusion with mild to moderate non-syndromic
craniofacial asymmetry were submitted to a clinical and X-ray evaluation.
Subjects with symmetric skeletal class I were used as the control group.
Evaluation of differences in postural pattern was performed using
rasterstereography. RESULTS: Statistical analysis (t-test) was performed on 61
patients divided in homogeneous subgroups. The results show a pelvic torsion
angle of 1.08 degrees + 3.00 degrees (P = 0.0023) (normal value (NV) = 0.0-1.9
degrees ) in subjects presenting skeletal class II z asymmetry (control group:
1.17 degrees +/- 1.25 degrees , not significant (NS)). CONCLUSIONS: The present
study shows evidence of a relationship between malocclusion and spinal posture. A
better understanding of the relationship between malocclusion and posture may
help in planning a multidisciplinary approach that could involve other
specialists.
PMID- 25845525
TI - Increased expression of neuropilin 1 is associated with epithelial ovarian
carcinoma.
AB - Neuropilin 1 (NRP1) is a transmembrane glycoprotein, which interacts with
vascular endothelial growth factor to prevent tumor cell apoptosis and to
regulate angiogenesis. However, the precise role of NRP1 in epithelial ovarian
carcinoma (EOC) remains to be elucidated. The present study aimed to determine
the association between NRP1 and EOC. The expression of NRP1 in ovarian cancer
and normal ovarian epithelial tissues was investigated by immunofluorescence,
reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and
western blotting. The association between the expression of NRP1 with the
development of ovarian cancer, clinicopathological characteristics and survival
were also analyzed. The results from immunofluorescence, RT-qPCR and western blot
analysis demonstrated that NRP1 exhibited significant upregulation in EOC
compared with normal ovarian epithelial specimens (P<0.05). The positive
expression of NRP1 was higher in cancer tissues at an advanced International
Federation of Gynecology and Obstetrics stage, and in cancer tissues with lymph
node metastasis and distant metastasis compared with that in cancer tissues
without lymph node or distant metastasis (P<0.05). Higher NRP1 expression
strongly predicted a shorter survival time (P<0.001). The present findings
suggested that increased NRP1 expression may be associated with the development
of EOC. Therefore, NRP1 could be used as a valuable prognostic marker as well as
a potential molecular therapy target for ovarian cancer patients.
PMID- 25845526
TI - The current preference for the immuno-analytical ELISA method for quantitation of
steroid hormones (endocrine disruptor compounds) in wastewater in South Africa.
AB - The availability of national test centers to offer a routine service for analysis
and quantitation of some selected steroid hormones [natural estrogens (17-beta
estradiol, E2; estrone, E1; estriol, E3), synthetic estrogen (17-alpha
ethinylestradiol, EE2), androgen (testosterone), and progestogen (progesterone)]
in wastewater matrix was investigated; corresponding internationally used
chemical- and immuno-analytical test methods were reviewed. The enzyme-linked
immunosorbent assay (ELISA) (immuno-analytical technique) was also assessed for
its suitability as a routine test method to quantitate the levels of these
hormones at a sewage/wastewater treatment plant (WTP) (Darvill, Pietermaritzburg,
South Africa), over a 2-year period. The method performance and other relevant
characteristics of the immuno-analytical ELISA method were compared to the
conventional chemical-analytical methodology, like gas/liquid chromatography-mass
spectrometry (GC/LC-MS), and GC-LC/tandem mass spectrometry (MSMS), for
quantitation of the steroid hormones in wastewater and environmental waters. The
national immuno-analytical ELISA technique was found to be sensitive (LOQ 5 ng/L,
LOD 0.2-5 ng/L), accurate (mean recovery 96%), precise (RSD 7-10%), and cost
effective for screening and quantitation of these steroid hormones in wastewater
and environmental water matrix. A survey of the most current international
literature indicates a fairly equal use of the LC-MS/MS, GC-MS/MS (chemical
analytical), and ELISA (immuno-analytical) test methods for screening and
quantitation of the target steroid hormones in both water and wastewater matrix.
Internationally, the observed sensitivity, based on LOQ (ng/L), for the steroid
estrogens E1, E2, EE2, is, in decreasing order: LC-MSMS (0.08-9.54) > GC-MS (1) >
ELISA (5) (chemical-analytical > immuno-analytical). At the national level, the
routine, unoptimized chemical-analytical LC-MSMS method was found to lack the
required sensitivity for meeting environmental requirements for steroid hormone
quantitation. Further optimization of the sensitivity of the chemical-analytical
LC-tandem mass spectrometry methods, especially for wastewater screening, in
South Africa is required. Risk assessment studies showed that it was not
practical to propose standards or allowable limits for the steroid estrogens E1,
E2, EE2, and E3; the use of predicted-no-effect concentration values of the
steroid estrogens appears to be appropriate for use in their risk assessment in
relation to aquatic organisms. For raw water sources, drinking water, raw and
treated wastewater, the use of bioassays, with trigger values, is a useful
screening tool option to decide whether further examination of specific endocrine
activity may be warranted, or whether concentrations of such activity are of low
priority, with respect to health concerns in the human population. The
achievement of improved quantitation limits for immuno-analytical methods, like
ELISA, used for compound quantitation, and standardization of the method for
measuring E2 equivalents (EEQs) used for biological activity (endocrine: e.g.,
estrogenic) are some areas for future EDC research.
PMID- 25845527
TI - Thermodynamic-based retention time predictions of endogenous steroids in
comprehensive two-dimensional gas chromatography.
AB - This work evaluates the application of a thermodynamic model to comprehensive two
dimensional gas chromatography (GC * GC) coupled with time-of-flight mass
spectrometry for anabolic agent investigation. Doping control deals with hundreds
of drugs that are prohibited in sports. Drug discovery in biological matrices is
a challenging task that requires powerful tools when one is faced with the
rapidly changing designer drug landscape. In this work, a thermodynamic model
developed for the prediction of both primary and secondary retention times in GC
* GC has been applied to trimethylsilylated hydroxyl (O-TMS)- and methoxime
trimethylsilylated carbonyl (MO-TMS)-derivatized endogenous steroids. This model
was previously demonstrated on a pneumatically modulated GC * GC system, and is
applied for the first time to a thermally modulated GC * GC system. Preliminary
one-dimensional experiments allowed the calculation of thermodynamic parameters
(DeltaH, DeltaS, and DeltaC p ) which were successfully applied for the
prediction of the analytes' interactions with the stationary phases of both the
first-dimension column and the second-dimension column. The model was able to
predict both first-dimension and second-dimension retention times with high
accuracy compared with the GC * GC experimental measurements. Maximum differences
of -8.22 s in the first dimension and 0.4 s in the second dimension were
encountered for the O-TMS derivatives of 11beta-hydroxyandrosterone and 11
ketoetiocholanolone, respectively. For the MO-TMS derivatives, the largest
discrepancies were from testosterone (9.65 ) for the first-dimension retention
times and 11-keto-etiocholanolone (0.4 s) for the second-dimension retention
times.
PMID- 25845528
TI - Hypermethylation of the tumor-suppressor cell adhesion molecule 1 in human
papillomavirus-transformed cervical carcinoma cells.
AB - Epigenetic modification at CpG islands located on the promoter regions of tumor
suppressor genes has been associated with tumor development in many human
cancers. Our study showed that the cell adhesion molecule 1 (CADM1) is
downregulated in human papillomavirus (HPV)-infected cervical cancer cell lines
via its hypermethylation and demethylation using 5-aza-2'-deoxycyticine (5-aza
dC) restored the expression of CADM1 protein. Overexpression of CADM1 inhibited
cell proliferation. p53 was involved in the regulation of CADM1. Our results
demonstrate that epigenetic alteration of CADM1 was more frequent in HPV-positive
cervical cancers and that restoration of CADM1 expression may be a potential
strategy for cervical cancer therapy.
PMID- 25845529
TI - The over-pruning hypothesis of autism.
AB - This article outlines the over-pruning hypothesis of autism. The hypothesis
originates in a neurocomputational model of the regressive sub-type (Thomas,
Knowland & Karmiloff-Smith, 2011a, 2011b). Here we develop a more general version
of the over-pruning hypothesis to address heterogeneity in the timing of
manifestation of ASD, including new computer simulations which reconcile the
different observed developmental trajectories (early onset, late onset,
regression) via a single underlying atypical mechanism; and which show how
unaffected siblings of individuals with ASD may differ from controls either by
inheriting a milder version of the pathological mechanism or by co-inheriting the
risk factors without the pathological mechanism. The proposed atypical mechanism
involves overly aggressive synaptic pruning in infancy and early childhood, an
exaggeration of a normal phase of brain development. We show how the hypothesis
generates novel predictions that differ from existing theories of ASD including
that (1) the first few months of development in ASD will be indistinguishable
from typical, and (2) the earliest atypicalities in ASD will be sensory and motor
rather than social. Both predictions gain cautious support from emerging
longitudinal studies of infants at-risk of ASD. We review evidence consistent
with the over-pruning hypothesis, its relation to other current theories
(including C. Frith's under-pruning proposal; C. Frith, 2003, 2004), as well as
inconsistent data and current limitations. The hypothesis situates causal
accounts of ASD within a framework of protective and risk factors (Newschaffer et
al., 2012); clarifies different versions of the broader autism phenotype (i.e.
the implication of observed similarities between individuals with autism and
their family members); and integrates data from multiple disciplines, including
behavioural studies, neuroscience studies, genetics, and intervention studies.
PMID- 25845530
TI - The influence of a peer-based HIV prevention intervention on conversation about
HIV prevention among people who inject drugs in Baltimore, Maryland.
AB - STEP into Action assessed the efficacy of a peer-based HIV prevention
intervention in reducing HIV risk behaviors among people who inject drugs (PWIDs)
in Baltimore. This analysis examined the effect of the intervention on the change
in frequency of conversation about HIV prevention topics over time. 114
participants were randomized into an experimental and 113 into a control group.
Data was collected prospectively at 6, 12, and 18 months. The experimental group
talked more frequently about HIV prevention topics compared to the control group
at 6-month visit. At 18 months relative risk ratios (RRR) remained statistically
significant for conversation about the danger of needle sharing (RRR = 3.21) and
condom use (RRR = 2.81). The intervention resulted in an increased conversation
about HIV prevention among PWIDs, but the sustainability past 6 months remained a
challenge; suggesting that interventions should be designed to constantly
reinforce communication about HIV prevention among PWIDs.
PMID- 25845531
TI - Understanding Consistent Condom Use Among Homeless Men Who Have Sex with Women
and Engage in Multiple Sexual Partnerships: A Path Analysis.
AB - Consistent condom use is the main strategy aimed at preventing individuals from
acquiring HIV through sexual intercourse. The mechanism of consistent condom use
among a high-risk homeless subpopulation-homeless men who have sex with women and
also engage in multiple sexual partnerships-remains unclear. This study
identified 182 homeless men who engaged in multiple sexual partnerships from a
representative sample of homeless men, who self-identified as heterosexual, using
meal line services in Downtown Los Angeles' Skid Row area. Information such as
participants' condom use psychosocial correlates, sexual risk behaviors, and
social network characteristics were collected. Results suggested that condom
efficacy is a potential intervening mechanism through which condom attitudes
(beta = -0.199; p = 0.005) and depression (beta = -0.156; p = 0.029) are
associated with an individual's consistent condom use. Having more network
members with whom participants talked about HIV prevention (beta = 0.051; p =
0.006) was also found to be associated with an individual's consistent condom
use. HIV prevention programs should focus on increasing their condom efficacy to
help reduce HIV risks among this vulnerable homeless subpopulation.
PMID- 25845532
TI - Internal heavy atom effects in phenothiazinium dyes: enhancement of intersystem
crossing via vibronic spin-orbit coupling.
AB - The effect of substituting the intra-cyclic sulphur of thionine by oxygen
(oxonine) and selenium (selenine) on the intersystem crossing (ISC) efficiency
has been studied using high level quantum mechanical methods. The ISC rate
constants are considerably increased when going from O towards Se while the
fluorescence rate constants remain unchanged. For the three dyes, all accessible
ISC channels are driven by vibronic spin-orbit coupling (SOC) between pipi*
states. The interplay between the ground and low-lying excited states has been
investigated in order to determine the dominant relaxation pathways. In oxonine
the relaxation to the ground state after photoexcitation in water proceeds
essentially via fluorescence from the S1(piHpiL*) bright state (kF = 2.10 * 10(8)
s(-1)), in agreement with the high experimental fluorescence quantum yield. In
aqueous solution of thionine, the ISC rate constant (kISC ~ 1 * 10(9) s(-1)) is
one order of magnitude higher than fluorescence (kF = 1.66 * 10(8) s(-1)) which
is consistent with its high triplet quantum yield observed in water (phiT =
0.53). Due to a stronger vibronic SOC in selenine, the ISC rate is very high
(kISC ~ 10(10) s(-1)) and much faster than fluorescence (kF = 1.59 * 10(8) s(
1)). This suggests selenine-based dyes as very efficient triplet
photosensitizers.
PMID- 25845534
TI - Medicalization of the Post-Museum: Interactivity and Diagnosis at the Brain and
Cognition Exhibit.
AB - The introduction of digital games and simulations into science museums has
prompted excitement about a new "post-museum" pedagogy emphasizing
egalitarianism, interactivity, and personalized approaches to learning. However,
many post-museums of science, this article aims to show, enact rhetorical
performances that lead visitors to narrowly targeted answers and hide the
authority of the expert in a play of tactile and affective activities, thus
operating in opposition to many of the basic ideals of the post-museum. The Brain
and Cognition Exhibit at the Hong Kong Science Museum serves as a case study for
how a post-museum exhibit, through embracing interactivity and visitor-centered
tasks, becomes a site where science is tested on and performed through visitors'
bodies such that institutional prescriptions are applied. Visitors are not merely
encouraged at this exhibit to learn about the brain through doing but are trained
to see functional and dysfunctional brains and to then diagnose themselves and
their children by playing games and taking brain-measurement tests. As a result,
the interactive engagement of the exhibit creates a new space of public
medicalization. Reflections and suggestions are offered at the end of the
article.
PMID- 25845535
TI - A sensitive and high throughput bacterial luminescence assay for assessing
aquatic toxicity--the BLT-Screen.
AB - Bioassays using naturally luminescent bacteria are commonly used to assess the
toxicity of environmental contaminants, detected by a decrease in luminescence.
Typically, this has involved the use of commercial test kits such as Microtox and
ToxScreen. These commercial assays, however, have limitations for routine
environmental monitoring, including the need for specialized equipment, a low
throughput and high on-going costs. There is therefore a need to develop a
bacteria bioassay that is sensitive, high-throughput and cost effective. This
study presents the development and application of the BLT-Screen (Bacterial
Luminescence Toxicity Screen), a 96-well plate bioassay using Photobacterium
leiognathi. During development of the method, the concentration of the phosphate
buffer in the experimental medium was adjusted to maximize the sensitivity of the
assay, and protocols for analyzing both solid-phase extracts and raw water
samples were established. A range of organic compounds and metals were analyzed
in the assay, as well as extracts of various water samples, including drinking
water, wastewater effluent and river water. The IC50 values of the organic
compounds and metals tested in the BLT-Screen were comparable to previously
published ToxScreen and Microtox data. In addition, the assay was sensitive
enough to detect toxicity in all water types tested, and performed equally well
for both solid-phase extracts and raw water samples. The BLT-Screen therefore
presents a cost-effective, sensitive and high throughput method for testing the
toxicity of environmental contaminants in a range of water types that has
widespread applications for research, as well as for routine monitoring and
operation of wastewater and drinking water plants.
PMID- 25845536
TI - Replicating poxviruses for human cancer therapy.
AB - Naturally occurring oncolytic viruses are live, replication-proficient viruses
that specifically infect human cancer cells while sparing normal cell
counterparts. Since the eradication of smallpox in the 1970s with the aid of
vaccinia viruses, the vaccinia viruses and other genera of poxviruses have shown
various degrees of safety and efficacy in pre-clinical or clinical application
for human anti-cancer therapeutics. Furthermore, we have recently discovered that
cellular tumor suppressor genes are important in determining poxviral oncolytic
tropism. Since carcinogenesis is a multi-step process involving accumulation of
both oncogene and tumor suppressor gene abnormalities, it is interesting that
poxvirus can exploit abnormal cellular tumor suppressor signaling for its
oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ATM,
and RB are known to play important roles in genomic fidelity/maintenance. Thus,
tumor suppressor gene abnormality could affect host genomic integrity and likely
disrupt intact antiviral networks due to accumulation of genetic defects, which
would in turn result in oncolytic virus susceptibility. This review outlines the
characteristics of oncolytic poxvirus strains, including vaccinia, myxoma, and
squirrelpox virus, recent progress in elucidating the molecular connection
between oncogene/tumor suppressor gene abnormalities and poxviral oncolytic
tropism, and the associated preclinical/clinical implications. I would also like
to propose future directions in the utility of poxviruses for oncolytic
virotherapy.
PMID- 25845538
TI - Multiple roles of a putative vacuolar protein sorting associated protein 74,
FgVPS74, in the cereal pathogen Fusarium graminearum.
AB - Fusarium graminearum, a member of the F. graminearum species complex, is a
filamentous ascomycetous group that causes serious diseases in cereal crops. A
screen of insertional mutants of F. graminearum, generated using a restriction
enzyme-mediated integration method, identified a mutant designated R7048 showing
pleiotropic phenotypes in several mycological traits. The vector insertion site
in the R7048 genome was identified as the KpnI site within an ORF annotated as
FGSG_06346 (designated FgVPS74), which showed similarity to vacuolar protein
sorting-associated protein 74 in the baker yeast. Both targeted gene deletion and
complementation analyses confirmed that FgVPS74 was involved in hyphal growth,
conidiation, sexual development, mycotoxin production, and virulence towards host
plants in F. graminearum. Electron microscopy analysis revealed no significant
changes in morphology of the vacuole or other organelles, but a greater number of
mitochondria were produced in the DeltaFgVPS74 strain compared to the wild-type
progenitor. Expression of a GFP-tagged FgVPS74 construct under its native
promoter in the DeltaFgVPS74 strain exhibited localization of GFP signal to
putative vesicle structures, but not to the vacuolar membrane. Taken together,
these findings demonstrated that a functional vacuolar protein-sorting pathway
mediated by FgVPS74 is crucial for fungal growth and development in F.
graminearum.
PMID- 25845537
TI - New record and enzyme activity of four species in Penicillium section Citrina
from marine environments in Korea.
AB - Several strains of Penicillium section Citrina were isolated during a survey of
fungi from marine environments along the southern coast of Korea. Based on
multigene phylogenetic analyses (beta-tubulin and calmodulin) and morphological
characteristics, the 11 strains were identified as P. citrinum, P.
hetheringtonii, P. paxilli, P. sumatrense, P. terrigenum, and P. westlingii. To
understand the ecological role of these species, we tested all strains for
extracellular enzyme activity; six strains representing four species showed beta
glucosidase activity. Four of the identified species - P. hetheringtonii, P.
paxilli, P. terrigenum, and P. westlingii - are new records for Korea. For these
new species records, we describe morphological characteristics of the strains and
compare results to published data of type strains.
PMID- 25845539
TI - Effect of promoter-upstream sequence on sigma38-dependent stationary phase gene
transcription.
AB - sigma38 in Escherichia coli is required for expression of a subset of stationary
phase genes. However, the promoter elements for sigma38-dependent genes are
virtually indistinguishable from that for sigma70-dependent house-keeping genes.
hdeABp is a sigma38-dependent promoter and LEE5p is a sigma70-dependent promoter,
but both are repressed by H-NS, a bacterial histone-like protein, which acts at
promoter upstream sequence. We swapped the promoter upstream sequences of the two
promoters and found that the sigma dependency was switched. This was further
verified using lacUV5 core promoter. The results suggested that the determinant
for sigma38-dependent promoter lies in the promoter upstream sequence.
PMID- 25845540
TI - Statistical experimental design optimization of rhamsan gum production by
Sphingomonas sp. CGMCC 6833.
AB - Rhamsan gum is a type of water-soluble exopolysaccharide produced by species of
Sphingomonas bacteria. The optimal fermentation medium for rhamsan gum production
by Sphingomonas sp. CGMCC 6833 was explored definition. Single-factor experiments
indicate that glucose, soybean meal, K(2)HPO(4) and MnSO(4) compose the optimal
medium along with and initial pH 7.5. To discover ideal cultural conditions for
rhamsan gum production in a shake flask culture, response surface methodology was
employed, from which the following optimal ratio was derived: 5.38 g/L soybean
meal, 5.71 g/L K(2)HPO(4) and 0.32 g/L MnSO(4). Under ideal fermentation rhamsan
gum yield reached 19.58 g/L +/- 1.23 g/L, 42.09% higher than that of the initial
medium (13.78 g/L +/- 1.38 g/L). Optimizing the fermentation medium results in
enhanced rhamsan gum production.
PMID- 25845542
TI - DNA in the Criminal Justice System: The DNA Success Story in Perspective.
AB - Current figures on the efficiency of DNA as an investigative tool in criminal
investigations only tell part of the story. To get the DNA success story in the
right perspective, we examined all forensic reports from serious (N = 116) and
high-volume crime cases (N = 2791) over the year 2011 from one police region in
the Netherlands. These data show that 38% of analyzed serious crime traces (N =
384) and 17% of analyzed high-volume crime traces (N = 386) did not result in a
DNA profile. Turnaround times (from crime scene to DNA report) were 66 days for
traces from serious crimes and 44 days for traces from high-volume crimes.
Suspects were truly identified through a match with the Offender DNA database of
the Netherlands in 3% of the serious crime cases and in 1% of the high-volume
crime cases. These data are important for both the forensic laboratory and the
professionals in the criminal justice system to further optimize forensic DNA
testing as an investigative tool.
PMID- 25845541
TI - Directed analysis of cyanobacterial membrane phosphoproteome using stained
phosphoproteins and titanium-enriched phosphopeptides.
AB - Gel-free shotgun phosphoproteomics of unicellular cyanobacterium Synechocystis
sp. PCC 6803 has not been reported up to now. The purpose of this study is to
develop directed membrane phosphoproteomic method in Synechocystis sp. Total
Synechocystis membrane proteins were separated by sodium dodecyl sulfate
polyacrylamide gel electrophoresis and phosphoprotein-stained gel bands were
selectively subjected to in-gel trypsin digestion. The phosphorylation sites of
the resulting peptides were determined by assigning the neutral loss of [M
H(3)PO(4)] to Ser, Thr, and Tyr residues using nano-liquid chromatography 7 Tesla
Fourier transform mass spectrometry. As an initial application, 111 proteins and
33 phosphoproteins were identified containing 11 integral membrane proteins.
Identified four unknown phosphoproteins with transmembrane helices were suggested
to be involved in membrane migration or transporters based on BLASTP search
annotations. The overall distribution of hydrophobic amino acids in pTyr was
lower in frequency than that of pSer or pThr. Positively charged amino acids were
abundantly revealed in the surrounding amino acids centered on pTyr. A directed
shotgun membrane phosphoproteomic strategy provided insight into understanding
the fundamental regulatory processes underlying Ser, Thr, and Tyr phosphorylation
in multi-layered membranous cyanobacteria.
PMID- 25845543
TI - Serum osteopontin levels are upregulated and predict disability after an
ischaemic stroke.
AB - BACKGROUND: After an acute ischaemic stroke (AIS), several inflammatory
biomarkers have been investigated, but their predictive role on functional
recovery remains to be validated. Here, we investigated the prognostic relevance
of biomarkers related to atherosclerotic plaque calcification, such as
osteopontin (OPN), osteoprotegerin (OPG) and the receptor activator of nuclear
factor kappa-B ligand (RANKL) in a cohort of patients with AIS (n = 90) during 90
day follow-up. MATERIALS AND METHODS: Radiological and clinical examinations as
well as blood sampling were performed at admission and at days 1, 7 and 90 from
the event. Validated scores [such as modified Rankin scale (mRS) and the National
Institutes of Health Stroke Scale (NIHSS)] were used to assess poststroke
outcome. Serum levels of OPN, OPG and RANKL were measured by colorimetric enzyme
linked immunosorbent assay (ELISA). RESULTS: When compared to the admission, OPN
serum levels increased at day 7. Serum OPN levels at this time point were
positively correlated with both ischaemic lesion volume and NIHSS at days 7 and
90. A cut-off of 30.53 ng/mL was identified for serum OPN by receiver operating
characteristic (ROC) curve analysis. Adjusted logistic regression showed that
serum OPN levels at day 7 predicted worse mRS at day 90 [OR 4.13 (95% CI 1.64
10.36); P = 0.002] and NIHSS [1.49 (95% CI 1.16-1.99); P = 0.007], independently
of age, gender, hypertension and thrombolysis. CONCLUSIONS: Serum levels of OPN,
but not OPG and RANKL, peaked at day 7 after AIS and predicted worse neurological
scores. Therefore, OPN might have a pathophysiological and clinical relevance
after AIS.
PMID- 25845544
TI - An open multicenter comparative randomized clinical study on chitosan.
AB - Chitosan, a natural polysaccharide derivate from chitin, offers a promising
alternative biomaterial for use in wound dressings. In this work, the safety and
efficacy of a next-generation KA01 chitosan wound dressing in facilitating the
healing of nonhealing chronic wounds was studied. This open multicenter
comparative prospective randomized clinical study was conducted at three medical
centers in China. A total of 90 patients (45 in test group and 45 in control
group) with unhealed chronic wounds including pressure ulcers, vascular ulcers,
diabetic foot ulcers, and wounds with minor infections, or at risk of infection,
were treated with the next generation chitosan wound dressing as the test article
or traditional vaseline gauze as a control. Baseline assessments were undertaken
with the primary end point being wound area reduction. The secondary end points
included pain reduction (using the NRS11 pain scale) at dressing change, wound
exudate levels, wound depth and duration of the treatment. After 4 weeks
treatment, the wound area reduction was significantly greater in the test group
(65.97 +/- 4.48%) than the control group (39.95 +/- 4.48%). The average pain
level in the test group was 1.12 +/- 0.23 and 2.30 +/- 0.23 in the control group.
The wound depth was also lower in the test group 0.30 +/- 0.48 cm than the
control group 0.54 +/- 0.86 cm. The level of exudate fell and the dressing could
be removed integrally in both the test and control groups. The mean duration of
the test group was 27.31 +/- 5.37 days and control group 27.09 +/- 6.44 days. No
adverse events were reported in either group. In conclusion this open multicenter
comparative prospective randomized clinical study has provided compelling
evidence that the next generation chitosan wound dressing can enhance wound
progression towards healing by facilitating wound reepithelialization and
reducing the patients pain level. Furthermore the dressing was shown to be
clinically safe and effective in the management of chronic wounds.
PMID- 25845545
TI - High Tumor Penetration of Paclitaxel Loaded pH Sensitive Cleavable Liposomes by
Depletion of Tumor Collagen I in Breast Cancer.
AB - The network of collagen I in tumors could prevent the penetration of drugs loaded
in nanoparticles, and this would lead to impaired antitumor efficacy. In this
study, free losartan (an angiotensin inhibitor) was injected before treatment to
reduce the level of collagen I, which could facilitate the penetration of
nanoparticles. Then the pH-sensitive cleavable liposomes (Cl-Lip) were injected
subsequently to exert the antitumor effect. The Cl-Lip was constituted by PEG(5K)
Hydrazone-PE and DSPE-PEG(2K)-R8. When the Cl-Lip reached to the tumor site by
the enhanced permeability and retention (EPR) effect, PEG(5K)-Hydrazone-PE was
hydrolyzed from the Cl-Lip under the low extra-cellular pH conditions of tumors,
then the R8 peptide was exposed, and finally liposomes could be internalized into
tumor cells by the mediation of R8 peptide. In vitro experiments showed both the
cellular uptake of Cl-Lip by 4T1 cells and cytotoxicity of paclitaxel loaded Cl
Lip (PTX-Cl-Lip) were pH sensitive. In vivo experiments showed the Cl-Lip had a
good tumor targeting ability. After depletion of collagen I, Cl-Lip could
penetrate into the deep place of tumors, the tumor accumulation of Cl-Lip was
further increased by 22.0%, and the oxygen distributed in tumor tissues was also
enhanced. The antitumor study indicated free losartan in combination with PTX-Cl
Lip (59.8%) was more effective than injection with PTX-Cl-Lip only (37.8%) in 4T1
tumor bearing mice. All results suggested that depletion of collagen I by
losartan dramatically increased the penetration of PTX-Cl-Lip and combination of
free losartan and PTX-CL-Lip could lead to better antitumor efficacy of chemical
drugs. Thus, the combination strategy might be a promising tactic for better
treatment of solid tumors with a high level of collagen I.
PMID- 25845546
TI - Mirror aneurysms of the proximal segment of the anterior cerebral artery.
PMID- 25845547
TI - Preemptive scalp infiltration with 0.5% ropivacaine and 1% lidocaine reduces
postoperative pain after craniotomy.
AB - BACKGROUND: In order to reduce the consequences of narcotic-related side effects
and provide effective analgesia after craniotomy, we conducted a randomized trial
to compare the analgesic efficacy of preemptive scalp infiltrations with 1%
lidocaine and 0.5% ropivacaine on the postoperative pain. METHODS: Sixty adult
patients scheduled for craniotomy were enrolled. A solution contained 0.5%
ropivacaine and 1% lidocaine (40 ml) was prepared. In group A, local anesthetic
was injected throughout the entire thickness of the scalp before skin incision.
In group B, it was injected before skin closure. Additional intravenous injection
and patient-controlled analgesia with morphine was used to control postoperative
pain if the verbal numerical rating scale > 4. Cumulative morphine consumption;
numerical rating scale of pain at 1, 2, 4, 6, 8, 12, and 24 h; postoperative
nausea, vomiting, and respiratory depression, were recorded for 24 h after the
operation. RESULTS: Postoperative pain scores were lower in group A than in group
B within the first 6 h after surgery. Mean time to demand for postoperative
analgesic was statistically (p < 0.001) delayed in group A 300 (240, 360) min
compared to group B 150 (105, 200) min. Ten patients in group A received morphine
analgesia was half less than 21 patients in group B (p < 0.006). The median
morphine consumption in 24 h after operation in group A 10.5 (8, 15) mg was less
than that in group B 28 (22.5, 30.5) mg (p < 0.001). CONCLUSIONS: Preemptive
scalp infiltration with 0.5% ropivacaine and 1% lidocaine provides effective
postoperative analgesia after craniotomy.
PMID- 25845548
TI - Combined endonasal and sublabial endoscopic transmaxillary approach to the
pterygopalatine fossa and orbital apex.
AB - BACKGROUND: The pterygopalatine fossa (PPF) and inferomedial orbital apex are
difficult regions for open neurosurgical access. The traditional extensive
anterior approach (transfacial or transmandibular) and lateral/posterolateral
(transcranial) approach were used to access the PPF. The combined endonasal and
sublabial transmaxillary approach is a less invasive access route for these
lesions. In this study, we present the technical and clinical details of our
experience with the combined endoscopic endonasal and transmaxillary approach.
METHODS: A retrospective analysis of our patients operated on using a combined
endoscopic endonasal and transmaxillary approach was done. The preoperative,
intraoperative and postoperative images and all the clinical data were evaluated.
The accessibility to the area and extent of surgical resection were reviewed. The
surgery-related complications and postoperative morbidities were analyzed. The
main items of interest were the exposure of the target area and possibility for
safe removal. RESULTS: Five patients with pathologies located in the area of the
PPF and orbital apex were operated on using the combined endoscopic sublabial and
endonasal transmaxillary approach. The technique provided sufficient exposure of
the area and allowed for safe removal of the preoperatively determined target in
all of the patients. One patient developed dry eye and a neurotrophic corneal
ulcer, and another patient developed temporary postoperative facial numbness. In
the follow-up, only one patient with skull base chordoma had an asymptomatic
tumor regrowth. The other patients had no recurrence or regrowth. CONCLUSIONS:
The combined endoscopic sublabial and endonasal transmaxillary approach is a safe
and effective method for resection of lesions in the PPF and inferomedial orbital
apex.
PMID- 25845549
TI - Tractography of Meyer's loop for temporal lobe resection-validation by prediction
of postoperative visual field outcome????.
AB - BACKGROUND: Postoperative visual field defects are common after temporal lobe
resection because of injury to the most anterior part of the optic radiation,
Meyer's loop. Diffusion tensor tractography is a promising technique for
visualizing the optic radiation preoperatively. The aim of this study was to
assess the anatomical accuracy of Meyer's loop, visualized by the two most common
tractography methods-deterministic (DTG) and probabilistic tractography (PTG)-in
patients who had undergone temporal lobe resection. METHODS: Eight patients with
temporal lobe resection for temporal lobe pathology were included. Perimetry and
diffusion tensor imaging were performed pre- and postoperatively. Two independent
operators analyzed the distance between the temporal pole and Meyer's loop (TP
ML) using DTG and PTG. Results were compared to each other, to data from
previously published dissection studies and to postoperative perimetry results.
For the latter, Spearman's rank correlation coefficient (r(s)) was used. RESULTS:
Median preoperative TP-ML distances for nonoperated sides were 42 and 35 mm, as
determined by DTG and PTG, respectively. TP-ML assessed with PTG was a closer
match to dissection studies. Intraclass correlation coefficients were 0.4 for DTG
and 0.7 for PTG. Difference between preoperative TP-ML (by DTG and PTG,
respectively) and resection length could predict the degree of postoperative
visual field defects (DTG: r(s) = -0.86, p < 0.05; PTG: r(s) = -0.76, p < 0.05).
CONCLUSION: Both DTG and PTG could predict the degree of visual field defects.
However, PTG was superior to DTG in terms of reproducibility and anatomical
accuracy. PTG is thus a strong candidate for presurgical planning of temporal
lobe resection that aims to minimize injury to Meyer's loop.
PMID- 25845550
TI - Incidence of local in-brain progression after supramarginal resection of cerebral
metastases.
AB - BACKGROUND: Microsurgical circumferential stripping of intracerebral metastases
is often insufficient in achieving local tumor control. Supramarginal resection
may improve local tumor control. METHODS: A retrospective analysis was performed
for patients who underwent supramarginal resection of a cerebral metastasis by
awake surgery with intraoperative cortical and subcortical stimulation, MEPs, and
SSEPs. Supramarginal resection was achieved by circumferential stripping of the
metastasis and additional removal of approximately 3 mm of the surrounding
tissue. Pre- and postsurgical neurological status was assessed by the NIH Stroke
Scale. Permanent deficits were defined by persistence after 3-month observation
time. RESULTS: Supramarginal resection of cerebral metastases in eloquent brain
areas was performed in 34 patients with a mean age of 60 years (range, 33-83
years). Five out of 34 patients (14.7%) had a new transient postoperative
neurological deficit, which improved within a few days due to supplementary motor
area (SMA) syndrome. Five out of 34 patients (14.7%) developed a local in-brain
progression and nine patients (26.4%) a distant in-brain progression.
CONCLUSIONS: Supramarginal resection of cerebral metastases in eloquent locations
is feasible and safe. Safety might be increased by intraoperative
neuromonitoring. The better outcome in the present series may be entirely based
on other predictors than extend of surgical resection and not necessarily on the
surgical technique applied. However, supramarginal resection was safe and
apparently did not lead to worse results than regular surgical techniques.
Prospective, controlled, and randomized studies are mandatory to determine the
possible benefit of supramarginal resection on local tumor control and overall
outcome.
PMID- 25845551
TI - Linear array ultrasound: a dedicated tool for a dedicated application.
PMID- 25845552
TI - Results of re-exploration because of compromised distal blood flow after clipping
unruptured intracranial aneurysms.
AB - BACKGROUND: One of the major causes for performing unplanned re-exploration of a
craniotomy after microsurgery for unruptured intracranial aneurysms (UIAs) is
compromised distal blood flow after clipping. Therefore, it is important to
identify the causes of compromised distal blood flow after clipping and the
factors that influence the prognosis for re-exploration in order to decrease
ischemic complications related to clipping UIAs. METHOD: Between January 2007 and
December 2013, 1954 patients underwent microsurgery for UIAs. In this cohort, 20
patients (1.0%) required unplanned re-exploration of the craniotomy for several
reasons, and 11 patients (0.6%) underwent unplanned re-exploration with clip
repositioning or changing of the previous clip because of compromised distal
blood flow after clipping. Patient characteristics, aneurysm properties,
intraoperative findings, annual incidence and prognosis were analyzed in these 11
patients. RESULTS: The annual incidence of re-exploration has gradually decreased
since the introduction of several intraoperative monitoring techniques. In total,
3.0% of UIAs in the M1 trunk, 0.8% of UIAs at the origin of the anterior
choroidal artery (AchA) and 0.5% of UIAs at the bifurcation of the middle
cerebral artery (MCA) required re-exploration. Here, all 11 UIAs had broad necks,
and atherosclerosis was identified around 10 UIAs. Six patients with compromised
MCA flow demonstrated relatively better outcomes following re-exploration than
five patients with a compromised lenticulostriate artery (LSA) or AchA flow. Four
patients with delayed ischemic symptoms demonstrated relatively better outcomes
than the seven patients who developed ischemic symptoms immediately
postoperatively. CONCLUSION: Clinicians need to be more careful not to compromise
distal blood flow when clipping UIAs at the MCA and AchA origin. Various
intraoperative monitoring techniques can help reduce the incidence of compromised
distal blood flow after clipping.
PMID- 25845553
TI - Total removal of a trigeminal schwannoma via the expanded endoscopic endonasal
approach. Technical note.
AB - BACKGROUND: Because of their deep location surrounded by closed numerous
neurovascular structures, skull base tumors of the cavernous sinus are still
difficult to manage. Recently, the endoscopic endonasal approach commonly used
for pituitary tumor resection has been "expanded" to the parasellar,
infratemporal and orbital compartments with some advantages compared to the
intracranial route. METHODS: The authors reported the case of a 49-year-old male
presenting a large extradural tumor of the left cavernous sinus with extensions
toward the orbit, sphenoid sinus and infratemporal fossa. His ophthalmological
examination was normal, and the body CT scan revealed no primary neoplasm.
RESULTS: In this operative video, the approach is described step by step with
surgical nuances. The endoscopy provided a close-up panoramic view and various
angles of vision. Also, it avoided an invasive craniotomy, cerebral retraction
and cranial nerves damages. Thus, it allowed the total removal of this tumor
originating from the maxillary branch of the trigeminal nerve. The pathologic
examination confirmed a schwannoma. CONCLUSION: The expanded endoscopic endonasal
approach provides an interesting corridor to cavernous sinus tumors with
satisfactory control of extensions inferiorly toward the infratemporal fossa,
anteriorly via the superior orbital fissure and medially within the sphenoid.
Finally, the skull base surgeon has to master this anterior endoscopic route as
well as all the other "open" transcranial skull base approaches to propose the
best surgical route fitting the tumor characteristics.
PMID- 25845554
TI - Superior lithium storage performance using sequentially stacked MnO2/reduced
graphene oxide composite electrodes.
AB - Hybrid nanostructures based on graphene and metal oxides hold great potential for
use in high-performance electrode materials for next-generation lithium-ion
batteries. Herein, a new strategy to fabricate sequentially stacked alpha-MnO2
/reduced graphene oxide composites driven by surface-charge-induced mutual
electrostatic interactions is proposed. The resultant composite anode exhibits an
excellent reversible charge/discharge capacity as high as 1100 mA h g(-1) without
any traceable capacity fading, even after 100 cycles, which leads to a high rate
capability electrode performance for lithium ion batteries. Thus, the proposed
synthetic procedures guarantee a synergistic effect of multidimensional nanoscale
media between one (metal oxide nanowire) and two dimensions (graphene sheet) for
superior energy-storage electrodes.
PMID- 25845555
TI - Allergy-test-driven elimination diet is useful in children with eosinophilic
esophagitis, regardless of the severity of symptoms.
AB - BACKGROUND: A combination of PPIs and corticosteroids is the pharmacotherapy
mostly used to treat eosinophilic esophagitis (EoE), while dietetic manipulations
consist also an efficient option. The aim of this study was to compare the
efficacy of allergy-test-driven elimination diet in children with mild symptoms
of EoE to a group of children with moderate/severe symptoms. METHODS: Thirty-five
children, aged 7 months to 12 yr, with EoE were enrolled in the study. They had a
clinical history of GERD-like (21 children, Group A) or more severe symptoms (14
children, Group B). The diagnosis had been confirmed after two preliminary months
of therapy with PPIs and an esophagogastroduodenoscopy. Soon after diagnosis,
they were allergy-tested, using IgE detection (SPT and serum-specific IgE) and
atopy patch tests (APTs). A 12-month tailor-made diet was prescribed according to
the tests. Patients of Group B continued PPIs for two more months, while
swallowed topical steroids were also prescribed to them for the first 5 months
after diagnosis, followed by an 'as-needed' use of them for the rest of the
study. Endoscopy was repeated at the end of the study. RESULTS: Milk and egg were
the most common APT-positive allergens. Thirty-two patients were instructed to
follow an elimination diet, which was completed by 15/18 of Group A and 12/14 of
Group B. An improvement of symptoms was reported by 26/27 patients that completed
the study. The use of swallowed corticosteroids was noticeably decreased during
the as-needed period, in Group B. A remarkable reduce of eosinophils was noticed
in biopsies; from 42.84 +/- 18.08, they decreased to 6.41 +/- 3.20, a year after.
CONCLUSION: All children with EoE and mild symptoms had resolution of symptoms
and normal eosinophils in the esophageal mucosa a year after an allergy-driven
elimination diet. Patients with moderate/severe EoE symptoms had the same
improvement, indicating that an elimination diet is an efficient complementary
treatment to corticosteroids.
PMID- 25845557
TI - Highly enantioselective transfer hydrogenation of ketones with chiral (NH)2 P2
macrocyclic iron(II) complexes.
AB - Bis(isonitrile) iron(II) complexes bearing a C2 -symmetric diamino (NH)2 P2
macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a
broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5
%), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading
(generally 0.1 mol %). The catalyst can be easily tuned by modifying the
substituents of the isonitrile ligand.
PMID- 25845556
TI - Tetraarsenic hexoxide demonstrates anticancer activity at least in part through
suppression of NF-kappaB activity in SW620 human colon cancer cells.
AB - Tetraarsenic hexoxide (As4O6) has been used in Korean traditional medicine for
the treatment of cancer since the late 1980's, and arsenic trioxide (As2O3) is
currently used as a chemotherapeutic agent. Previous studies suggest that the
As4O6-induced cell death pathway is different from that of As2O3 and its
mechanism of anticancer activity remains unclear. Nuclear factor (NF)-kappaB is a
well-known transcription factor involved in cell proliferation, invasion and
metastasis. Hence, in the present study, we investigated the effects of As4O6 on
NF-kappaB activity and NF-kappaB-regulated gene expression in vitro and in vivo.
The cytotoxicity assay revealed that As4O6 inhibited the growth of SW620 cells in
a dose-dependent manner, and the half maximal inhibitory concentration (IC50) was
~1 uM after a 48 h treatment. As4O6 suppressed NF-kappaB activation and
suppressed inhibitory kappaBalpha (IkappaBalpha) phosphorylation stimulated by
tumor necrosis factor (TNF). As4O6 also suppressed downstream NF-kappaB-regulated
proteins involved in cancer anti-apoptosis, proliferation, invasion and
metastasis. In addition, As4O6 marginally suppressed tumor growth and the anti-NF
kappaB activity was confirmed using an in vivo xenograft mouse model in which
animals were injected with SW620 cells. The present study provides evidence that
As4O6 has anticancer properties through suppression of NF-kappaB activity and NF
kappaB-mediated cellular responses.
PMID- 25845558
TI - Isolation and purification of monosialotetrahexosylgangliosides from pig brain by
extraction and liquid chromatography.
AB - Monosialotetrahexosylganglioside (GM1), one of glycosphingolipids containing
sialic acid, plays particularly important role in fighting against paralysis,
dementia and other diseases caused by brain and nerve damage. In this work, a
simple and highly efficient method with high yield was developed for isolation
and purification of GM1 from pig brain. The method consisted of an extraction by
chloroform-methanol-water and a two-step chromatographic separation by DEAE
Sepharose Fast Flow anion-exchange medium and Sephacryl S-100 HR size-exclusion
medium. The purified GM1 was proved to be homogeneous and had a purity of >98.0%
by high-performance anion-exchange and size-exclusion chromatography. The
molecular weight was 30.0 kDa by high-performance size-exclusion chromatography
and 1546.9 Da by electrospray ionization mass spectrometry. The chromogenic
reaction by resorcinol-hydrochloric acid solution indicated that the purified GM1
showed a specific chromogenic reaction of sialic acid. Through this isolation and
purification program, ~1.0 mg of pure GM1 could be captured from 500 g wet pig
brain tissue and the yield of GM1 was around 0.022%, which was higher than the
yields by other methods. The method may provide an alternative for isolation and
purification of GM1 in other biological tissues.
PMID- 25845559
TI - The WNT system: background and its role in bone.
AB - WNTs are extracellular proteins that activate different cell surface receptors
linked to canonical and noncanonical WNT signalling pathways. The Wnt genes were
originally discovered as important for embryonic development of fruit flies and
malignant transformation of mouse mammary cancers. More recently, WNTs have been
implicated in a wide spectrum of biological phenomena and diseases. During the
last decade, several lines of clinical and preclinical evidence have indicated
that WNT signalling is critical for trabecular and cortical bone mass, and this
pathway is currently an attractive target for drug development. Based on detailed
knowledge of the different WNT signalling pathways, it appears that it might be
possible to develop drugs that specifically target cortical and trabecular bone.
Neutralization of a bone-specific WNT inhibitor is now being evaluated as a
promising anabolic treatment for patients with osteoporosis. Here, we provide the
historical background to the discoveries of WNTs, describe the different WNT
signalling pathways and summarize the current understanding of how these proteins
regulate bone mass by affecting bone formation and resorption.
PMID- 25845560
TI - Response to: 'Standard excision and reconstruction as an alternative to MMS for
giant basal cell carcinoma? - Commentary'.
PMID- 25845561
TI - Screening of cannabinoids in industrial-grade hemp using two-dimensional liquid
chromatography coupled with acidic potassium permanganate chemiluminescence
detection.
AB - Widely known for its recreational use, the cannabis plant also has the potential
to act as an antibacterial agent in the medicinal field. The analysis of cannabis
plants/products in both pharmacological and forensic studies often requires the
separation of compounds of interest and/or accurate identification of the whole
cannabinoid profile. In order to provide a complete separation and detection of
cannabinoids, a new two-dimensional liquid chromatography method has been
developed using acidic potassium permanganate chemiluminescence detection, which
has been shown to be selective for cannabinoids. This was carried out using a
Luna 100 A CN column and a Poroshell 120 EC-C18 column in the first and second
dimensions, respectively. The method has utilized a large amount of the available
separation space with a spreading angle of 48.4 degrees and a correlation of
0.66 allowing the determination of more than 120 constituents and mass spectral
identification of ten cannabinoids in a single analytical run. The method has the
potential to improve research involved in the characterization of sensitive,
complex matrices.
PMID- 25845562
TI - Toll-like receptors.
AB - The mammalian Toll-like receptor (TLR) family consists of 13 members, and
recognizes specific patterns of microbial components, called pathogen-associated
molecular patterns (PAMPs). TLR-dependent recognition of PAMPs leads to
activation of the innate immune system, which subsequently leads to activation of
antigen-specific adaptive immunity. The TLR-mediated signaling pathways consist
of the MyD88-dependent pathway and TRIF-dependent pathway, both of which induce
gene expression. This unit discusses mammalian TLRs (TLR1 to 13) that have an
essential role in the innate immune recognition of microorganisms. Also discussed
are TLR-mediated signaling pathways and antibodies that are available to detect
specific TLRs.
PMID- 25845563
TI - Measurement of bacterial ingestion and killing by macrophages.
AB - This unit presents assays that allow accurate measurement of phagocytosis and
killing of bacteria by macrophages. The first basic protocol describes how to
measure the ability of macrophages to ingest bacteria. Importantly, because
macrophage phagocytosis entails separate binding and internalization steps,
assays are described here that will also determine the extent to which bacteria
bound to the macrophage are in fact internalized. Two effective methods to do
this are described in alternate protocols. Both of these alternate protocols rely
on enumeration of differentially labeled bacteria by fluorescence microscopy to
distinguish intracellular from extracellular bacteria. The unit also presents two
protocols to measure the ability of a macrophage to kill bacteria it has
internalized. The second basic is a straightforward assay in which bacterial
colonies are enumerated before and after a killing period. Bactericidal activity
is evidenced by reduced CFU bacteria on agar plates. Because it is critical to
remove residual extracellular organisms, the protocol presents two alternative
steps to accomplish this: a washing procedure and a more stringent method in
which cells are sedimented through sucrose. An alternate protocol describes a way
to measure bacterial viability based on bacterial metabolism, in which the
ability of bacterial dehydrogenases to mediate the reduction of a tetrazolium
salt to purple formazan is monitored by measuring absorbance
spectrophotometrically.
PMID- 25845564
TI - Heymann nephritis in Lewis rats.
AB - Human membranous nephritis is a major cause of end-stage kidney disease. Active
Heymann nephritis (HN) is an auto-immune model of membranous nephritis induced in
Lewis rats by immunization with a crude renal tubular antigen (Fx1A) or megalin
(gp330). The pathogenesis of HN is through the binding of anti-Fx1A
autoantibodies to the auto-antigen expressed on glomerular epithelial cells,
resulting in severe glomerular injury and proteinuria. The pathological features
of HN include immune deposits in glomeruli and infiltration of glomeruli and the
tubulointerstitium by macrophages and T cells. This unit describes the method of
the preparation of Fx1A and the induction of HN in Lewis rats by immunization
with Fx1A.
PMID- 25845565
TI - Use of proteasome inhibitors.
AB - Proteasome inhibitors are indispensable research tools in immunology and cell
biology. With numerous proteasome inhibitors available commercially, choosing the
appropriate compound for a biological experiment may be challenging, especially
for a novice. This unit provides an overview of the proteasome inhibitors
commonly used in research. It discusses how to select an appropriate highly
specific inhibitor, its concentration, and length of exposure for mammalian cell
culture experiments. In addition, assays that can be used to confirm proteasome
inhibition are discussed.
PMID- 25845567
TI - Quantifying the severity of hurricanes on extinction probabilities of a primate
population: Insights into "Island" extirpations.
AB - Long-term studies quantifying impacts of hurricane activity on growth and
trajectory of primate populations are rare. Using a 14-year monitored population
of Alouatta palliata mexicana as a study system, we developed a modeling
framework to assess the relative contribution of hurricane disturbance and two
types of human impacts, habitat loss, and hunting, on quasi-extinction risk. We
found that the scenario with the highest level of disturbance generated a 21%
increase in quasi-extinction risk by 40 years compared to scenarios of
intermediate disturbance, and around 67% increase relative to that found in low
disturbance scenarios. We also found that the probability of reaching quasi
extinction due to human disturbance alone was below 1% by 40 years, although such
scenarios reduced population size by 70%, whereas the risk of quasi-extinction
ranged between 3% and 65% for different scenarios of hurricane severity alone, in
absence of human impacts. Our analysis moreover found that the quasi-extinction
risk driven by hunting and hurricane disturbance was significantly lower than the
quasi-extinction risk posed by human-driven habitat loss and hurricane
disturbance. These models suggest that hurricane disturbance has the potential to
exceed the risk posed by human impacts, and, in particular, to substantially
increase the speed of the extinction vortex driven by habitat loss relative to
that driven by hunting. Early mitigation of habitat loss constituted the best
method for reducing quasi-extinction risk: the earlier habitat loss is halted,
the less vulnerable the population becomes to hurricane disturbance. By using a
well-studied population of A. p. mexicana, we help understand the demographic
impacts that extreme environmental disturbance can trigger on isolated
populations of taxa already endangered in other systems where long-term
demographic data are not available. For those experiencing heavy anthropogenic
pressure and lacking sufficiently evolved coping strategies against unpredictable
environmental disturbance, the risk of population extinction can be exacerbated.
PMID- 25845566
TI - Altered relation between lipopolysaccharide-induced inflammatory response and
excitotoxicity in rat organotypic hippocampal slice cultures during ethanol
withdrawal.
AB - BACKGROUND: Ethanol (EtOH) causes neurotoxicity by several mechanisms including
excitotoxicity and neuroinflammation, but little is known about the interaction
between these mechanisms. Because neuroinflammation is known to enhance
excitotoxicity, we hypothesized that neuroinflammation contributes to the
enhanced excitotoxicity, which is associated with EtOH withdrawal (EWD). The aim
of this study was to evaluate the lipopolysaccharide (LPS)-induced inflammatory
response of cultured hippocampal tissue during EWD and its effects on the
enhanced N-methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity, which
occurs at this time. METHODS: Using a neonatal organotypic hippocampal slice
culture (OHSC) model, we assessed the effects of NMDA and LPS (separately or
combined) during EWD after 10 days of EtOH exposure. Neurotoxicity was assessed
using propidium iodide uptake, and the inflammatory response was evaluated by
measuring the release of tumor necrosis factor (TNF)-alpha (quantified by enzyme
linked immunosorbent assay) and nitric oxide (NO; quantified by the Griess
reaction) into culture media. Furthermore, we explored the potential role of the
microglial cell type using immortalized BV2 microglia treated with EtOH for 10
days and challenged with LPS during EWD. RESULTS: As predicted, NMDA-induced
toxicity was potentiated by LPS under control conditions. However, during EWD,
the reverse was observed and LPS inhibited peak NMDA-induced toxicity.
Additionally, LPS-induced release of TNF-alpha and NO during EWD was reduced
compared to control conditions. In BV2 microglia, following EtOH exposure, LPS
induced release of NO was reduced, whereas TNF-alpha release was potentiated.
CONCLUSIONS: During EWD following chronic EtOH exposure, OHSC exhibited a
desensitized inflammatory response to LPS and the effects of LPS on NMDA toxicity
were reversed. This might be explained by a change in microglia to an anti
inflammatory and neuroprotective phenotype. In support, studies on BV2 microglia
indicate that EtOH exposure and EWD do alter the response of these cells to LPS,
but this cannot fully explain the changes observed in the OHSC. The data suggest
that neuroinflammation and excitotoxicity do interact during EWD. However, the
interaction is not as simple as we originally proposed. This in turn illustrates
the need to assess the extent, importance, and relation of these mechanisms in
models of EtOH exposure producing neurotoxicity.
PMID- 25845575
TI - Caffeic acid, a phyto polyphenol mitigates fluoride induced hepatotoxicity in
rats: A possible mechanism.
AB - Fluoride induced hepatotoxicity has been extensively studied in both humans and
animals. However, the mechanism underlying in the hepatotoxicity of experimental
fluorosis remains obscure. The severity of fluoride toxicity was reduced by oral
administration of certain plant derived antioxidants. Caffeic acid (CA) a
polyphenolic compound has diverse range of pharmacological activity in the
biological system. Therefore, the present study was aimed to investigate the
protective mechanism of CA, against fluoride induced hepatotoxicity in rats. The
rats were treated with 300 ppm of NaF via drinking water ad libitum alone and in
combination with CA at a dose of 50 mg/kg daily for 30 days by oral intubation.
CA treatment significantly prevented fluoride induced hepatic damage as evident
from the histopathological studies and declined levels of serum fluoride and
liver marker enzymes. A significant decrease in the levels of enzymatic (SOD2,
CAT, GPx, and GSTpi class) and nonenzymatic (GSH and Vitamin C) antioxidants
along with increased ROS, lipid peroxidation, protein carbonyl content, and
nitrate levels by fluoride were also prevented in these groups. In addition, CA
inhibits fluoride induced apoptosis by altering the Bax and caspase-3p20
expressions. Further, fluoride induced upregulation of Nox4, p38alpha MAPK,
Hsp60, and downregulation of Hsp27 are the indicators for the detection of
oxidative damage, apoptosis, and mitochondrial stress was also modulated by CA.
These findings reveal that CA supplementation has a protective effect against
fluoride induced hepatotoxicity in rats.
PMID- 25845576
TI - Regional segmentation of ventricular models to achieve repolarization dispersion
in cardiac electrophysiology modeling.
AB - The electrocardiogram (ECG) is one of the most significant outputs of a
computational model of cardiac electrophysiology because it relates the numerical
results to clinical data and is a universal tool for diagnosing heart diseases.
One key features of the ECG is the T-wave, which is caused by longitudinal and
transmural heterogeneity of the action potential duration (APD). Thus, in order
to model a correct wave of repolarization, different cell properties resulting in
different APDs must be assigned across the ventricular wall and longitudinally
from apex to base. To achieve this requirement, a regional parametrization of the
heart is necessary. We propose a robust approach to obtain the transmural and
longitudinal segmentation in a general heart geometry without relying on ad hoc
procedures. Our approach is based on auxiliary harmonic lifting analyses, already
used in the literature to generate myocardial fiber orientations. Specifically,
the solution of a sequence of Laplace boundary value problems allows
parametrically controlled segmentation of both heart ventricles. The flexibility
and simplicity of the proposed method is demonstrated through several
representative examples, varying the locations and extents of the epicardial,
midwall, and endocardial layers. Effects of the control parameters on the T-wave
morphology are illustrated via computed ECGs.
PMID- 25845577
TI - Evolving characteristics and outcome of secondary acute promyelocytic leukemia
(APL): A prospective analysis by the French-Belgian-Swiss APL group.
AB - BACKGROUND: Reports of patients with secondary acute promyelocytic leukemia (APL)
have increased in recent years, particularly for those who received treatment
with mitoxantrone, and retrospective studies have suggested that their
characteristics and outcomes were similar to those of patients with de novo APL.
METHODS: The authors investigated patients with de novo and secondary APL who
were included in the ongoing APL-2006 trial. Patients with secondary APL who were
included in that trial also were compared with a previous retrospective cohort of
patients with secondary APL. RESULTS: In the APL-2006 trial, 42 of 280 patients
(15%) had secondary APL. Compared with the retrospective cohort, patients with
secondary APL in the APL-2006 trial had a lower incidence of prior breast
carcinoma (35.7% vs 57%; P = .03) and a higher incidence of prior prostate
carcinoma (26.2% vs 4.7%; P < .001). Treatment of the primary tumor in the APL
2006 trial less frequently included combined radiochemotherapy (28.6% vs 47.2%; P
= .044) and no mitoxantrone (0% vs 46.7%; P = .016) but more frequently included
anthracyclines (53.3% vs 38.3%; P = .015). In the APL-2006 trial, patients who
had secondary APL, compared with those who had de novo APL, were older (mean,
60.2 years vs 48.7 years, respectively; P < .0001) but had a similar complete
response rate (97.6% vs 90.3%, respectively), cumulative incidence of relapse (0%
vs 1.8%, respectively), and overall survival (92.3% vs 90.9%, respectively) at 18
months. CONCLUSIONS: Although the incidence of secondary APL appears to be stable
over time, evolving strategies for the treatment of primary cancers have reduced
its occurrence among breast cancer patients but have increased its incidence
among patients with prostate cancer. The current results confirm prospectively
that patients with secondary APL have characteristics and outcomes similar to
those of patients with de novo APL.
PMID- 25845578
TI - Pulmonary nodules in liver transplant candidates with hepatocellular carcinoma:
Imaging characteristics and clinical outcomes.
AB - No guidelines exist for the management of pulmonary nodules in patients with
hepatocellular carcinoma (HCC) who are being evaluated for liver transplantation.
The 172 patients with HCC who were listed for liver transplant at our institution
received both pretransplant chest computed tomography (CT) and follow-up CT.
Pulmonary nodules on CT were characterized and followed on subsequent scans by a
blinded radiologist, with a consensus review with a second radiologist being
performed for equivocal cases. Nodule characteristics and outcomes were examined
with chi-square tests, and the posttransplant survival of patients with different
nodule outcomes was compared. Cumulative probabilities of waiting-list removal
for nontransplant patients and cumulative probabilities of undergoing
transplantation for all patients were also compared between patients with and
without pulmonary nodules. Of all the patients, 76.2% had at least 1 pulmonary
nodule on pretransplant CT, with 301 total nodules characterized; 2.7% of nodules
represented HCC metastases, 1.0% represented other bronchopulmonary malignancies,
and 2.7% represented infections. None of the malignant nodules exhibited a
triangular/lentiform shape or calcifications. There were no statistically
significant differences in pulmonary nodule outcomes between patients who
underwent transplantation and those who did not undergo transplantation. No
significant differences in posttransplant survival were found between patients
with different nodule outcomes. There was also no significant difference between
patients with and without nodules in the cumulative probabilities of waiting-list
removal. However, the cumulative probability of undergoing liver transplantation
was borderline significantly higher in patients without pulmonary nodules. In
conclusion, despite the low prevalence of malignant nodules, all pulmonary
nodules besides triangular/lentiform-shaped or calcified nodules should be
followed with serial CT while the patient is on the transplant list, with biopsy
performed for new and/or enlarged nodules. Both malignancy and active infection
must be excluded when one is confronted with enlarged pulmonary nodules.
Clinicians should also be aware of the possibility of reactivation of a
granulomatous infection after transplantation.
PMID- 25845579
TI - CLINICAL CONSEQUENCES OF THE REVISED DSM-5 DEFINITION OF AGORAPHOBIA IN TREATMENT
SEEKING ANXIOUS YOUTH.
AB - BACKGROUND: In DSM-5, the agoraphobia core symptom criterion has been revised to
require fear about multiple situations from across at least two distinct domains
in which escape might be difficult or panic-like symptoms might develop. The
present study examined patterns and correlates of the recent change in a sample
of anxious youth with symptom presentations consistent with the DSM-IV
agoraphobia definition and/or specific phobia (SP) to consider how the recent
diagnostic change impacts the prevalence and composition of agoraphobia in
children and adolescents. METHOD: Analyses (N = 151) evaluated impairment and
correlates of agoraphobic youth who no longer meet the DSM-5 agoraphobia criteria
relative to agoraphobic youth who do meet the new DSM-5 criteria. Secondary
analyses compared agoraphobic youth not meeting DSM-5 criteria to SP youth.
RESULTS: One-quarter of youth with symptom presentations consistent with the DSM
IV agoraphobia definition no longer met criteria for DSM-5 agoraphobia, but
showed comparable severity and impairment across most domains to youth who do
meet criteria for DSM-5 agoraphobia. Further, these youth showed higher levels of
anxiety sensitivity and internalizing psychopathology relative to youth with SP.
CONCLUSIONS: A substantial proportion of impaired youth with considerable
agoraphobic symptom presentations have been left without a specified anxiety
diagnosis by the DSM-5, which may affect their ability to receive and/or get
coverage for services and their representation in treatment evaluations. Future
DSM iterations may do well to include a "circumscribed" agoraphobia specifier
that would characterize presentations of fear or anxiety about multiple
situations, but that do not span across at least two distinct situational
domains.
PMID- 25845580
TI - Characterization of facial phenotypes of children with congenital hypopituitarism
and their parents: a matched case-control study.
AB - Congenital Hypopituitarism (CH) has traditionally been associated with specific
facial phenotypes subsumed under the term midface retrusion, based on
cephalometric studies. In this study, we used a systematic anthropometric
approach to facial morphology in 37 individuals with CH and their parents,
primarily of French Canadian ancestry, and compared them to a control group of 78
French Canadian patients with well-controlled type 1 diabetes and their parents.
We were able to demonstrate clear morphological differences, which were more
prevalent in the affected group than in the control group. More specifically, we
showed the presence of a shorter skull base width (P < 0.001) and reduced inner
canthal distance (P = 0.006) in the CH face, as well as a relative
underdevelopment of the mandible (P = 0.001). These findings were present in
individuals of all ages, and were independent of the duration of growth hormone
treatment (median treatment 90.8 months; range 7.2-175.8 months). In addition,
skull base width was significantly reduced in both mothers and fathers of
affected children compared to the parents of the controls (P < 0.001), despite
comparable parental heights, supporting an underlying genetic etiology. Such
extensive phenotypic studies have not been done in congenital hypopituitarism and
will provide further opportunities for data mining.
PMID- 25845581
TI - Sensitive imaging of magnetic nanoparticles for cancer detection by active
feedback MR.
AB - PURPOSE: Sensitive imaging of superparamagnetic nanoparticles or aggregates is of
great importance in MR molecular imaging and medical diagnosis. For this purpose,
a conceptually new approach, termed active feedback magnetic resonance, was
developed. METHODS: In the presence of the Zeeman field, a dipolar field is
induced by the superparamagnetic nanoparticles or aggregates. Such dipolar field
creates spatial and temporal (due to water diffusion) variations to the
precession frequency of the nearby water 1 H magnetization. Sensitive imaging of
magnetic nanoparticles or aggregates can be achieved by manipulating the
intrinsic spin dynamics by selective self-excitation and fixed-point dynamics
under active feedback fields. RESULTS: Phantom experiments of superparamagnetic
nanoparticles; in vitro experiments of brain tissue with blood clots; and in vivo
mouse images of colon cancers, with and without labeling by magnetic
nanoparticles, suggest that this new approach provides enhanced, robust, and
positive contrast in imaging magnetic nanoparticles or aggregates for cancer
detection. CONCLUSION: The spin dynamics originated from selective self
excitation and fixed-point dynamics under active feedback fields have been shown
to be sensitive to dipolar fields generated by magnetic nanoparticles. Magn Reson
Med 74:33-41, 2015. (c) 2014 Wiley Periodicals, Inc.
PMID- 25845582
TI - Calcium channel blocker use and risk of Parkinson's disease: a meta-analysis.
AB - PURPOSES: Whether calcium channel blocker (CCB) use contributes to a low risk of
developing a first time diagnosis of Parkinson's disease (PD) remains
controversial. We conducted a meta-analysis to investigate the relationship
between CCB use and PD risk. METHODS: Pubmed, EMBASE, China National Knowledge
Infrastructure, and WanFang databases were searched for papers through May 2014.
Studies investigating the association between CCB use and the risk of first time
diagnosis of PD were included. Pooled adjusted risk ratio (RR) and 95% confidence
interval (CI) were calculated using a fixed-effect model. RESULTS: Five studies
involving 208 248 CCB users were identified. Overall, CCB use was associated with
a reduction in PD risk (RR = 0.76, 95%CI = 0.68-0.84) compared with the controls.
Subgroup analysis showed that dihydropyridine CCB use reduced by 27% PD risk (RR
= 0.73, 95%CI = 0.64-0.83) and non-dihydropyridine CCB use reduced by 30% PD risk
(RR = 0.70, 95%CI = 0.50-0.93). CONCLUSIONS: Overall, CCB use as a class is
associated with a reduction in PD risk. Both of dihydropyridine and non
dihydropyridine CCB use appear to reduce the risk of developing a first time
diagnosis of PD. More well-designed prospective studies are needed to investigate
the difference of the subtype of CCB user on PD risk.
PMID- 25845583
TI - Salt stress response of membrane proteome of sugar beet monosomic addition line
M14.
AB - Understanding how plants respond to and tolerate salt stress is important for
engineering and breeding effort to boost plant productivity and bioenergy in an
ever challenging environment. Sugar beet M14 line is a unique germplasm that
contains genetic materials from Beta vulgaris L. and Beta corolliflora Zoss, and
it exhibits tolerance to salt stress. Here we report the changes in membrane
proteome of the M14 plants in response to salt stress (0, 200, 400mM NaCl) using
an iTRAQ two-dimensional LC-MS/MS technology for quantitative proteomic analysis.
In total, 274 proteins, mostly membrane proteins, were identified, and 50
proteins exhibited differential protein level changes, with 40 proteins increased
and 10 decreased. The proteins were mainly involved in transport, metabolism,
protein synthesis, photosynthesis, protein folding and degradation, signal
transduction, stress and defense, energy, and cell structure. These results have
revealed interesting mechanisms underlying the M14 response and tolerance to salt
stress. BIOLOGICAL SIGNIFICANCE: Sugar beet monosomic addition line M14 is a
special variety with salt stress tolerance. Analysis of the M14 membrane proteome
under salt stress may provide useful information regarding specific adaptive
mechanisms underlying salt stress tolerance. Membrane proteins are known to play
critical roles in salt stress signaling and adaptation. The purpose of this study
was to identify significantly changed membrane proteins and determine their
possible relevance to salt tolerance. The proteomic analysis of the M14 line
revealed important molecular mechanisms that can be potentially applied to
improving crop salt tolerance. This article is part of a Special Issue entitled:
Proteomics in India.
PMID- 25845584
TI - Proteomic analysis of the response of Escherichia coli to short-chain fatty
acids.
AB - Given their simple and easy-to-manipulate chemical structures, short-chain fatty
acids (SCFAs) are valuable feedstocks for many industrial applications. While the
microbial production of SCFAs by engineered Escherichia coli has been
demonstrated recently, productivity and yields are limited by their antimicrobial
properties. In this work, we performed a comparative proteomic analysis of E.
coli under octanoic acid stress (15 mM) and identified the underlying mechanisms
of SCFA toxicity. Out of a total of 33 spots differentially expressed at a p
value <= 0.05, nine differentially expressed proteins involved in transport and
structural roles (OmpF, HPr, and FliC), oxidative stress (SodA, SodB, and TrxA),
protein synthesis (PPiB and RpsA) and metabolic functions (HPr, PflB) were
selected for further investigation. Our studies suggest that membrane damage and
oxidative stress are the main routes of inhibition by SCFAs in E. coli. The outer
membrane porin OmpF had the greatest impact on SCFA tolerance. Intracellular pH
analysis on ompF mutants grown under octanoic acid stress indicated that this
porin facilitates transport of SCFAs into the cell. The same response was
observed under hexanoic acid stress, further supporting the role of OmpF in
response to the presence of SCFAs. Furthermore, analysis of membrane protein
expression revealed that other outer membrane porins are also involved in the
response of E. coli to SCFAs. BIOLOGICAL SIGNIFICANCE: This work covers the first
known proteomic analysis to assess the inhibitory effect of SCFAs in E. coli.
SCFAs are molecules of great interest in the industry, but their microbial
production is limited by their antimicrobial properties. This work allowed
identification of differentially expressed proteins in response to SCFA stress
and demonstrated the relevance of short- and medium-chain FA transport across the
cell membrane via outer membrane porins, providing valuable insights on the
toxicity mechanism of SCFAs in E. coli. These results could also benefit future
engineering efforts by guiding the design and construction of industrial strains
that produce SCFAs with increased tolerance and productivity.
PMID- 25845585
TI - New insights into the human brain proteome: Protein expression profiling of deep
brain stimulation target areas.
AB - Deep brain stimulation (DBS) is a neurosurgical procedure that provides
therapeutic benefits for movement and affective disorders. The nucleus basalis of
Meynert (NBM) and substantia nigra (SN) are considered target areas to apply DBS.
Even though the degeneration of NBM and SN underlies the cognitive decline
observed in neurological diseases, the protein knowledge derived from both areas
is scarce. We have characterized the proteome present in both subcortical brain
areas using the Triple TOF 5600 mass spectrometer, identifying 2775 and 3469
proteoforms in NBM and SN respectively. Data mining of MS-generated proteomic
data have revealed that: i) 675 proteins tend to localize to synaptic ending, ii)
61% of the global dataset is also present in human CSF and/or plasma, and iii)
894 proteins have not been previously identified in healthy brain by MS. The
correlation of NBM and SN proteomic expression profiles with human brain
transcriptome data available at Allen Brain Atlas has revealed protein evidence
for 250 genes considered with brain-wide expression and 112 genes with region
specific expression in human brain. In addition, protein datasets have been
classified according to their chromosomal origin, increasing the current proteome
coverage in healthy human brain. BIOLOGICAL SIGNIFICANCE: The nucleus basalis of
Meynert and substantia nigra are brain areas of clinical interest to apply the
deep brain stimulation (DBS) technology in neurosurgery. Our proteomic
characterization has revealed 675 proteins involved in the regulation of synaptic
transmission, electrical machinery, and neurotransmitter release in both DBS
target areas. Moreover, 2599 identified proteins present capacity to be secreted
to the CSF and plasma. Our data contribute to a further step towards the
characterization of the anatomical atlas of the human brain proteome, detecting
652 proteins that are common between different basal ganglia structures. This
article is part of a Special Issue entitled: HUPO 2014.
PMID- 25845586
TI - iTRAQ-based quantitative proteomic analysis of Pseudomonas aeruginosa SJTD-1: A
global response to n-octadecane induced stress.
AB - N-octadecane, the shortest solid-state alkane, was efficiently consumed by
Pseudomonas aeruginosa SJTD-1. To reveal its mechanism, the iTRAQ-LC-MS/MS
strategy was applied for quantification of proteins in response to alkane. As a
result, 383 alkane-responsive proteins were identified and these proteins could
be linked to multiple biochemical pathways. Above all, the level of alkane
hydroxylase AlkB2 has been significantly higher in alkane condition. Also, the
presence of a putative novel AlmA-like monooxygenase and its role on alkane
hydroxylation were firstly proposed in Pseudomonas. In addition, other proteins
for chemotaxic, beta-oxidation, glyoxylate bypass, alkane uptake, cross membrane
transport, enzymatic steps and the carbon flow may have important roles in the
cellular response to alkane. Most of those differently expressed proteins were
functionally mapped into pathways of alkane degradation or metabolism thereof. In
this sense, findings in this study provide critical clues to reveal
biodegradation of long chain n-alkanes and rationally be important for potent
biocatalyst for bioremediation in future. BIOLOGICAL SIGNIFICANCE: We use iTRAQ
strategy firstly to compare the proteomes of Pseudomonas SJTD-1 degrading alkane.
Changes in protein clearly provide a comprehensive overview on alkane
hydroxylation of SJTD-1, including those proteins for chemotaxis, alkane uptake,
cross membrane transport, enzymatic steps and the carbon flow. AlkB2 and a
putative novel AlmA-like monooxygenase have been highlighted for their
outstanding contribution to alkane use. We found that several chemotaxic proteins
were altered in abundance in alkane-grown cells. These results may be helpful for
understanding alkane use for Pseudomonas.
PMID- 25845587
TI - Non-chemotherapy drug-induced agranulocytosis in a tertiary hospital.
AB - Drug-induced agranulocytosis is a rare haematological disorder considered as
severe adverse drug reaction. Due to its low incidence, the number of studies are
low and the variability of clinical features and presentation in hospitalized
patients is rarely described. Awe performed an observational, transversal and
retrospective study in the haematology and toxicology unit in a tertiary hospital
located in Spain (Valencia) (1996-2010) in order to assess its incidence, the
drugs involved, the management and outcomes of drug-induced agranulocytosis.
Twenty-one cases of agranulocytosis were retrieved. All of them presented severe
and symptomatic agranulocytosis (fever and infection). The most common drug
associated with drug-induced agranulocytosis was metamizole administration but
other drugs belonging to different pharmacological classes as well (carbimazol,
sulfasalazine, bisoprolol, itraconazole, amitryptiline, ketorolac and
claritomicine+cefuroxime). No differences between sex and age were found in
relationship with the manifestations or course of agranulocytosis. In contrast, a
significantly negative association was found between age of patients and the
percentage of increase in neutrophil count. Administration of human granulocyte
colony-stimulating factor did not significantly enhance the recovery of the
process or the restoration of leucocytes count, suggesting a limited utility in
this type of agranulocytosis.
PMID- 25845588
TI - Reprint of: A healthy island blue space: From space of detention to site of
sanctuary.
AB - Island blue spaces are associated with restorative potential, but few studies
examine this proposition when an island's use has changed over time. We examine
Rotoroa Island (near Auckland, New Zealand) where, for almost a century, the
Salvation Army ran an alcohol treatment facility. The island's relative isolation
was central to its mixed therapeutic and carceral roles. Following change in
treatment ideologies, the facility closed in 2005. It subsequently re-opened as a
reserve for recreation, remembrance and environmental restoration. Our analysis
focuses on the enabling resources at Rotoroa across these two eras, in the
context of different constructions of healthy island blue space.
PMID- 25845589
TI - A universal strategy for regulating mRNA translation in prokaryotic and
eukaryotic cells.
AB - We describe a simple strategy to control mRNA translation in both prokaryotic and
eukaryotic cells which relies on a unique protein-RNA interaction. Specifically,
we used the Pumilio/FBF (PUF) protein to repress translation by binding in
between the ribosome binding site (RBS) and the start codon (in Escherichia
coli), or by binding to the 5' untranslated region of target mRNAs (in mammalian
cells). The design principle is straightforward, the extent of translational
repression can be tuned and the regulator is genetically encoded, enabling the
construction of artificial signal cascades. We demonstrate that this approach can
also be used to regulate polycistronic mRNAs; such regulation has rarely been
achieved in previous reports. Since the regulator used in this study is a modular
RNA-binding protein, which can be engineered to target different 8-nucleotide RNA
sequences, our strategy could be used in the future to target endogenous mRNAs
for regulating metabolic flows and signaling pathways in both prokaryotic and
eukaryotic cells.
PMID- 25845590
TI - Splicing factor SRSF1 negatively regulates alternative splicing of MDM2 under
damage.
AB - Genotoxic stress induces alternative splicing of the oncogene MDM2 generating
MDM2-ALT1, an isoform attributed with tumorigenic properties. However, the
mechanisms underlying this event remain unclear. Here we explore MDM2 splicing
regulation by utilizing a novel minigene that mimics endogenous MDM2 splicing in
response to UV and cisplatinum-induced DNA damage. We report that exon 11 is
necessary and sufficient for the damage-specific alternative splicing of the MDM2
minigene and that the splicing factor SRSF1 binds exon 11 at evolutionarily
conserved sites. Interestingly, mutations disrupting this interaction proved
sufficient to abolish the stress-induced alternative splicing of the MDM2
minigene. Furthermore, SRSF1 overexpression promoted exclusion of exon 11, while
its siRNA-mediated knockdown prevented the stress-induced alternative splicing of
endogenous MDM2. Additionally, we observed elevated SRSF1 levels under stress and
in tumors correlating with the expression of MDM2-ALT1. Notably, we demonstrate
that MDM2-ALT1 splicing can be blocked by targeting SRSF1 sites on exon 11 using
antisense oligonucleotides. These results present conclusive evidence supporting
a negative role for SRSF1 in MDM2 alternative splicing. Importantly, we define
for the first time, a clear-cut mechanism for the regulation of damage-induced
MDM2 splicing and present potential strategies for manipulating MDM2 expression
via splicing modulation.
PMID- 25845591
TI - Heat-induced ribosome pausing triggers mRNA co-translational decay in Arabidopsis
thaliana.
AB - The reprogramming of gene expression in heat stress is a key determinant to
organism survival. Gene expression is downregulated through translation
initiation inhibition and release of free mRNPs that are rapidly degraded or
stored. In mammals, heat also triggers 5'-ribosome pausing preferentially on
transcripts coding for HSC/HSP70 chaperone targets, but the impact of such
phenomenon on mRNA fate remains unknown. Here, we provide evidence that, in
Arabidopsis thaliana, heat provokes 5'-ribosome pausing leading to the XRN4
mediated 5'-directed decay of translating mRNAs. We also show that hindering
HSC/HSP70 activity at 20 degrees C recapitulates heat effects by inducing
ribosome pausing and co-translational mRNA turnover. Strikingly, co-translational
decay targets encode proteins with high HSC/HSP70 binding scores and hydrophobic
N-termini, two characteristics that were previously observed for transcripts most
prone to pausing in animals. This work suggests for the first time that stress
induced variation of translation elongation rate is an evolutionarily conserved
process leading to the polysomal degradation of thousands of 'non-aberrant'
mRNAs.
PMID- 25845592
TI - Molecular crowding enhances facilitated diffusion of two human DNA glycosylases.
AB - Intracellular space is at a premium due to the high concentrations of
biomolecules and is expected to have a fundamental effect on how large
macromolecules move in the cell. Here, we report that crowded solutions promote
intramolecular DNA translocation by two human DNA repair glycosylases. The
crowding effect increases both the efficiency and average distance of DNA chain
translocation by hindering escape of the enzymes to bulk solution. The increased
contact time with the DNA chain provides for redundant damage patrolling within
individual DNA chains at the expense of slowing the overall rate of damaged base
removal from a population of molecules. The significant biological implication is
that a crowded cellular environment could influence the mechanism of damage
recognition as much as any property of the enzyme or DNA.
PMID- 25845593
TI - Uncoupling histone turnover from transcription-associated histone H3
modifications.
AB - Transcription in eukaryotes is associated with two major changes in chromatin
organization. Firstly, nucleosomal histones are continuously replaced by new
histones, an event that in yeast occurs predominantly at transcriptionally active
promoters. Secondly, histones become modified post-translationally at specific
lysine residues. Some modifications, including histone H3 trimethylation at
lysine 4 (H3K4me3) and acetylation at lysines 9 (H3K9ac) and 14 (H3K14ac), are
specifically enriched at active promoters where histones exchange, suggesting a
possible causal relationship. Other modifications accumulate within transcribed
regions and one of them, H3K36me3, is thought to prevent histone exchange. Here
we explored the relationship between these four H3 modifications and histone
turnover at a few selected genes. Using lysine-to-arginine mutants and a histone
exchange assay, we found that none of these modifications plays a major role in
either promoting or preventing histone turnover. Unexpectedly, mutation of H3K56,
whose acetylation occurs prior to chromatin incorporation, had an effect only
when introduced into the nucleosomal histone. Furthermore, we used various
genetic approaches to show that histone turnover can be experimentally altered
with no major consequence on the H3 modifications tested. Together, these results
suggest that transcription-associated histone turnover and H3 modification are
two correlating but largely independent events.
PMID- 25845594
TI - Specificity of the ModA11, ModA12 and ModD1 epigenetic regulator N(6)-adenine DNA
methyltransferases of Neisseria meningitidis.
AB - Phase variation (random ON/OFF switching) of gene expression is a common feature
of host-adapted pathogenic bacteria. Phase variably expressed N(6)-adenine DNA
methyltransferases (Mod) alter global methylation patterns resulting in changes
in gene expression. These systems constitute phase variable regulons called
phasevarions. Neisseria meningitidis phasevarions regulate genes including
virulence factors and vaccine candidates, and alter phenotypes including
antibiotic resistance. The target site recognized by these Type III N(6)-adenine
DNA methyltransferases is not known. Single molecule, real-time (SMRT) methylome
analysis was used to identify the recognition site for three key N. meningitidis
methyltransferases: ModA11 (exemplified by M.NmeMC58I) (5'-CGY M6A: G-3'), ModA12
(exemplified by M.Nme77I, M.Nme18I and M.Nme579II) (5'-AC M6A: CC-3') and ModD1
(exemplified by M.Nme579I) (5'-CC M6A: GC-3'). Restriction inhibition assays and
mutagenesis confirmed the SMRT methylome analysis. The ModA11 site is complex and
atypical and is dependent on the type of pyrimidine at the central position, in
combination with the bases flanking the core recognition sequence 5'-CGY M6A: G
3'. The observed efficiency of methylation in the modA11 strain (MC58) genome
ranged from 4.6% at 5'-GCGC M6A: GG-3' sites, to 100% at 5'-ACGT M6A: GG-3'
sites. Analysis of the distribution of modified sites in the respective genomes
shows many cases of association with intergenic regions of genes with altered
expression due to phasevarion switching.
PMID- 25845595
TI - Reconstructing genome-scale metabolic models with merlin.
AB - The Metabolic Models Reconstruction Using Genome-Scale Information (merlin) tool
is a user-friendly Java application that aids the reconstruction of genome-scale
metabolic models for any organism that has its genome sequenced. It performs the
major steps of the reconstruction process, including the functional genomic
annotation of the whole genome and subsequent construction of the portfolio of
reactions. Moreover, merlin includes tools for the identification and annotation
of genes encoding transport proteins, generating the transport reactions for
those carriers. It also performs the compartmentalisation of the model,
predicting the organelle localisation of the proteins encoded in the genome and
thus the localisation of the metabolites involved in the reactions promoted by
such enzymes. The gene-proteins-reactions (GPR) associations are automatically
generated and included in the model. Finally, merlin expedites the transition
from genomic data to draft metabolic models reconstructions exported in the SBML
standard format, allowing the user to have a preliminary view of the biochemical
network, which can be manually curated within the environment provided by merlin.
PMID- 25845596
TI - The EMBL-EBI bioinformatics web and programmatic tools framework.
AB - Since 2009 the EMBL-EBI Job Dispatcher framework has provided free access to a
range of mainstream sequence analysis applications. These include sequence
similarity search services (https://www.ebi.ac.uk/Tools/sss/) such as BLAST,
FASTA and PSI-Search, multiple sequence alignment tools
(https://www.ebi.ac.uk/Tools/msa/) such as Clustal Omega, MAFFT and T-Coffee, and
other sequence analysis tools (https://www.ebi.ac.uk/Tools/pfa/) such as
InterProScan. Through these services users can search mainstream sequence
databases such as ENA, UniProt and Ensembl Genomes, utilising a uniform web
interface or systematically through Web Services interfaces
(https://www.ebi.ac.uk/Tools/webservices/) using common programming languages,
and obtain enriched results with novel visualisations. Integration with EBI
Search (https://www.ebi.ac.uk/ebisearch/) and the dbfetch retrieval service
(https://www.ebi.ac.uk/Tools/dbfetch/) further expands the usefulness of the
framework. New tools and updates such as NCBI BLAST+, InterProScan 5 and
PfamScan, new categories such as RNA analysis tools
(https://www.ebi.ac.uk/Tools/rna/), new databases such as ENA non-coding,
WormBase ParaSite, Pfam and Rfam, and new workflow methods, together with the
retirement of depreciated services, ensure that the framework remains relevant to
today's biological community.
PMID- 25845597
TI - A common tRNA modification at an unusual location: the discovery of wyosine
biosynthesis in mitochondria.
AB - Establishment of the early genetic code likely required strategies to ensure
translational accuracy and inevitably involved tRNA post-transcriptional
modifications. One such modification, wybutosine/wyosine is crucial for
translational fidelity in Archaea and Eukarya; yet it does not occur in Bacteria
and has never been described in mitochondria. Here, we present genetic, molecular
and mass spectromery data demonstrating the first example of wyosine in
mitochondria, a situation thus far unique to kinetoplastids. We also show that
these modifications are important for mitochondrial function, underscoring their
biological significance. This work focuses on TyW1, the enzyme required for the
most critical step of wyosine biosynthesis. Based on molecular phylogeny, we
suggest that the kinetoplastids pathways evolved via gene duplication and
acquisition of an FMN-binding domain now prevalent in TyW1 of most eukaryotes.
These findings are discussed in the context of the extensive U-insertion RNA
editing in trypanosome mitochondria, which may have provided selective pressure
for maintenance of mitochondrial wyosine in this lineage.
PMID- 25845598
TI - A functional screen identifies miRNAs that inhibit DNA repair and sensitize
prostate cancer cells to ionizing radiation.
AB - MicroRNAs (miRNAs) have been implicated in DNA repair pathways through
transcriptional responses to DNA damaging agents or through predicted miRNA
regulation of DNA repair genes. We hypothesized that additional DNA damage
regulating miRNAs could be identified by screening a library of 810 miRNA
mimetics for the ability to alter cellular sensitivity to ionizing radiation
(IR). A prostate cancer Metridia luciferase cell model was applied to examine the
effects of individual miRNAs on IR sensitivity. A large percentage of miRNA
mimetics were found to increase cellular sensitivity to IR, while a smaller
percentage were protective. Two of the most potent IR sensitizing miRNAs, miR-890
and miR-744-3p, significantly delayed IR induced DNA damage repair. Both miRNAs
inhibited the expression of multiple components of DNA damage response and DNA
repair. miR-890 directly targeted MAD2L2, as well as WEE1 and XPC, where miR-744
3p directly targeted RAD23B. Knock-down of individual miR-890 targets by siRNA
was not sufficient to ablate miR-890 radiosensitization, signifying that miR-890
functions by regulating multiple DNA repair genes. Intratumoral delivery of miR
890 mimetics prior to IR therapy significantly enhanced IR therapeutic efficacy.
These results reveal novel miRNA regulation of DNA repair and identify miR-890 as
a potent IR sensitizing agent.
PMID- 25845599
TI - Nuclear pore components affect distinct stages of intron-containing gene
expression.
AB - Several nuclear pore-associated factors, including the SUMO-protease Ulp1, have
been proposed to prevent the export of intron-containing messenger
ribonucleoparticles (mRNPs) in yeast. However, the molecular mechanisms of this
nuclear pore-dependent mRNA quality control, including the sumoylated targets of
Ulp1, have remained unidentified. Here, we demonstrate that the apparent 'pre
mRNA leakage' phenotype arising upon ULP1 inactivation is shared by sumoylation
mutants of the THO complex, an early mRNP biogenesis factor. Importantly, we
establish that alteration of THO complex activity differentially impairs the
expression of intronless and intron-containing reporter genes, rather than
triggering bona fide 'pre-mRNA leakage'. Indeed, we show that the presence of
introns within THO target genes attenuates the effect of THO inactivation on
their transcription. Epistasis analyses further clarify that different nuclear
pore components influence intron-containing gene expression at distinct stages.
Ulp1, whose maintenance at nuclear pores depends on the Nup84 complex, impacts on
THO-dependent gene expression, whereas the nuclear basket-associated Mlp1/Pml39
proteins prevent pre-mRNA export at a later stage, contributing to mRNA quality
control. Our study thus highlights the multiplicity of mechanisms by which
nuclear pores contribute to gene expression, and further provides the first
evidence that intronic sequences can alleviate early mRNP biogenesis defects.
PMID- 25845600
TI - Structures of Escherichia coli DNA adenine methyltransferase (Dam) in complex
with a non-GATC sequence: potential implications for methylation-independent
transcriptional repression.
AB - DNA adenine methyltransferase (Dam) is widespread and conserved among the gamma
proteobacteria. Methylation of the Ade in GATC sequences regulates diverse
bacterial cell functions, including gene expression, mismatch repair and
chromosome replication. Dam also controls virulence in many pathogenic Gram
negative bacteria. An unexplained and perplexing observation about Escherichia
coli Dam (EcoDam) is that there is no obvious relationship between the genes that
are transcriptionally responsive to Dam and the promoter-proximal presence of
GATC sequences. Here, we demonstrate that EcoDam interacts with a 5-base pair non
cognate sequence distinct from GATC. The crystal structure of a non-cognate
complex allowed us to identify a DNA binding element, GTYTA/TARAC (where Y = C/T
and R = A/G). This element immediately flanks GATC sites in some Dam-regulated
promoters, including the Pap operon which specifies pyelonephritis-associated
pili. In addition, Dam interacts with near-cognate GATC sequences (i.e. 3/4-site
ATC and GAT). Taken together, these results imply that Dam, in addition to being
responsible for GATC methylation, could also function as a methylation
independent transcriptional repressor.
PMID- 25845601
TI - Gadd45a promotes DNA demethylation through TDG.
AB - Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have
been implicated in DNA demethylation in vertebrates. However, it remained unclear
how they contribute to the demethylation process. Here, we demonstrate that
Gadd45a promotes active DNA demethylation through thymine DNA glycosylase (TDG)
which has recently been shown to excise 5-formylcytosine (5fC) and 5
carboxylcytosine (5caC) generated in Ten-eleven-translocation (Tet)-initiated
oxidative demethylation. The connection of Gadd45a with oxidative demethylation
is evidenced by the enhanced activation of a methylated reporter gene in HEK293T
cells expressing Gadd45a in combination with catalytically active TDG and Tet.
Gadd45a interacts with TDG physically and increases the removal of 5fC and 5caC
from genomic and transfected plasmid DNA by TDG. Knockout of both Gadd45a and
Gadd45b from mouse ES cells leads to hypermethylation of specific genomic loci
most of which are also targets of TDG and show 5fC enrichment in TDG-deficient
cells. These observations indicate that the demethylation effect of Gadd45a is
mediated by TDG activity. This finding thus unites Gadd45a with the recently
defined Tet-initiated demethylation pathway.
PMID- 25845602
TI - Formaldehyde inhalation during pregnancy abolishes the development of acute
innate inflammation in offspring.
AB - Formaldehyde (FA) is an environmental and occupational pollutant that induces
programming mechanisms on the acquired immune host defense in offspring when
exposed during the prenatal period. Hence, here we investigated whether the
exposure of FA on pregnant rats could affect the development of an innate acute
lung injury in offspring induced by lipopolissacaride (LPS) injection. Pregnant
Wistar rats were exposed to FA (0.92 mg/m(3)) or vehicle (distillated water),
both 1 h/day, 5 days/week, from 1 to 21 days of pregnancy. Non-manipulated rats
were used as control. After 30 days of birth, the offspring was submitted to
injection of LPS (Salmonella abortus equi, 5 mg/kg, i.p.). Systemic and lung
inflammatory parameters were evaluated 24 h later. Exposure to FA during
gestation abolished the development of acute lung injury in offspring, as
observed by reduced number of leukocytes in the bronchoalveolar fluid (BAL), in
the blood and in the bone marrow, and decreased myeloperoxidase activity in the
lung. Moreover, phagocytes from BAL presented normal phagocytosis, but reduced
oxidative burst. Alterations on the profile of inflammatory cytokines were
evidenced by reduced mRNA levels of IL-6 and elevated levels of IL-10 and IFN
gamma in the lung tissue. Indeed, mRNA levels of toll-likereceptor-4 and nuclear
factor-kappa B translocation into the nucleus were also reduced. Additionally,
hyperresponsiveness to methacholine was blunted in the trachea of offspring of FA
exposed mothers. Together, our data clearly show that FA exposure in the prenatal
period modifies the programming mechanisms of the innate defense in the offspring
leading to impaired defense against infections.
PMID- 25845603
TI - Determination of Urinary PAH Metabolites Using DLLME Hyphenated to Injector Port
Silylation and GC-MS-MS.
AB - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants
and well-known carcinogens. Hydroxy derivatives of PAH are considered as
biomarkers of PAH exposure, and there is a need to measure these metabolites at
low concentrations. So, a precise and eco-friendly analytical method has been
developed for rapid determination of PAH metabolites. For the first time, a new
analytical method based on coupling of dispersive liquid-liquid microextraction
(DLLME) with auto-injector port silylation (auto-IPS) followed by gas
chromatography-tandem mass spectrometry (GC-MS-MS) analysis is reported for the
analysis of seven urinary PAH metabolites. Factors affecting DLLME and IPS, such
as type and volume of extraction and disperser solvent, pH, ionic strength,
injector port temperature, volume of N,O-bis(trimethylsilyl)trifluoroacetamide
and type of solvent were investigated. Under optimized conditions, the limit of
detection and limit of quantification were found to be in the range of 1-9 and 3
29 ng/mL, respectively. Satisfactory recoveries of metabolites in urine samples
in the range of 87-95% were found. The developed method has been successfully
applied for the determination of PAH metabolites in urine samples of exposed
workers. DLLME-auto-IPS-GC-MS-MS method is time, labor, solvent and reagent
saving, which can be routinely used for the analysis of urinary PAH metabolites.
PMID- 25845604
TI - Volatile substance abuse: fatal overdose with dimethylether.
PMID- 25845606
TI - What Is the Clinical Utility of Bedside Ultrasonography in the Diagnosis of Acute
Cardiogenic Pulmonary Edema in the Undifferentiated Dyspneic Patient?
PMID- 25845605
TI - A conserved proline residue in Dothideomycete Avr4 effector proteins is required
to trigger a Cf-4-dependent hypersensitive response.
AB - CfAvr4, a chitin-binding effector protein produced by the Dothideomycete tomato
pathogen Cladosporium fulvum, protects the cell wall of this fungus against
hydrolysis by secreted host chitinases during infection. However, in the presence
of the Cf-4 immune receptor of tomato, CfAvr4 triggers a hypersensitive response
(HR), which renders the pathogen avirulent. Recently, several orthologues of
CfAvr4 have been identified from phylogenetically closely related species of
Dothideomycete fungi. Of these, DsAvr4 from Dothistroma septosporum also triggers
a Cf-4-dependent HR, but CaAvr4 and CbAvr4 from Cercospora apii and Cercospora
beticola, respectively, do not. All, however, bind chitin. To identify the
region(s) and specific amino acid residue(s) of CfAvr4 and DsAvr4 required to
trigger a Cf-4-dependent HR, chimeric and mutant proteins, in which specific
protein regions or single amino acid residues, respectively, were exchanged
between CfAvr4 and CaAvr4 or DsAvr4 and CbAvr4, were tested for their ability to
trigger an HR in Nicotiana benthamiana plants transgenic for the Cf-4 immune
receptor gene. Based on this approach, a single region common to CfAvr4 and
DsAvr4 was determined to carry a conserved proline residue necessary for the
elicitation of this HR. In support of this result, a Cf-4-dependent HR was
triggered by mutant CaAvr4 and CbAvr4 proteins carrying an arginine-to-proline
substitution at this position. This study provides the first step in deciphering
how Avr4 orthologues from different Dothideomycete fungi trigger a Cf-4-dependent
HR.
PMID- 25845607
TI - Derivation and Internal Validation of the Ebola Prediction Score for Risk
Stratification of Patients With Suspected Ebola Virus Disease.
AB - STUDY OBJECTIVE: The current outbreak of Ebola virus disease in West Africa is
the largest on record and has overwhelmed the capacity of local health systems
and the international community to provide sufficient isolation and treatment of
all suspected cases. The goal of this study is to develop a clinical prediction
model that can help clinicians risk-stratify patients with suspected Ebola virus
disease in the context of such an epidemic. METHODS: A retrospective analysis was
performed of patient data collected during routine clinical care at the Bong
County Ebola Treatment Unit in Liberia during its first 16 weeks of operation.
The predictive power of 14 clinical and epidemiologic variables was measured
against the primary outcome of laboratory-confirmed Ebola virus disease, using
logistic regression to develop a final prediction model. Bootstrap sampling was
used to assess the internal validity of the model and estimate its performance in
a simulated validation cohort. RESULTS: Ebola virus disease testing results were
available for 382 (97%) of 395 patients admitted to the Ebola treatment unit
during the study period. A total of 160 patients (42%) tested positive for Ebola
virus disease. Logistic regression analysis identified 6 variables independently
predictive of laboratory-confirmed Ebola virus disease, including sick contact,
diarrhea, loss of appetite, muscle pains, difficulty swallowing, and absence of
abdominal pain. The Ebola Prediction Score, constructed with these 6 variables,
had an area under the receiver operator characteristic curve of 0.75 (95%
confidence interval 0.70 to 0.80) for the prediction of laboratory-confirmed
Ebola virus disease. Patients with higher Ebola Prediction Scores had higher
likelihoods of laboratory-confirmed Ebola virus disease. CONCLUSION: The Ebola
Prediction Score can be used by clinicians as an adjunct to current Ebola virus
disease case definitions to risk-stratify patients with suspected Ebola virus
disease. Clinicians can use this new tool for the purpose of cohorting patients
within the suspected-disease ward of an Ebola treatment unit or community-based
isolation center to prevent nosocomial infection or as a triage tool when patient
numbers overwhelm available capacity. Given the inherent limitations of clinical
prediction models, however, a low-cost, point-of-care test that can rapidly and
definitively exclude Ebola virus disease in patients should be a research
priority.
PMID- 25845608
TI - Rates of residual disease with close but negative margins in breast cancer
surgery.
AB - OBJECTIVES: A recent multidisciplinary consensus defined an adequate breast
cancer margin as no ink on tumor. The purpose of this study was to analyze rates
of residual disease at re-excision by margin width. MATERIALS AND METHODS: A
prospective database at a single institution was reviewed from 2000 to 2012.
Institutional protocol had been to perform re-excision surgery when margins were
<2 millimeters (mm). RESULTS: There were 2520 procedures. Re-excision surgery was
performed for 12% of breast conserving therapy (BCT) procedures and 2% of
mastectomies; residual disease was present in 38% and 26%, respectively. The
rates of residual disease for all patients with positive, 0.1-0.9 mm, and 1.0-1.9
mm margins were 40%, 38%, and 33%, respectively. Age, race, menopause status,
width of closest final margin, tumor histology, hormone receptor status, triple
negative disease and presence of lymphovascular invasion (LVI) were not
significantly associated with the presence of residual disease. The presence of
multiple margins <2 mm trended toward significance (p = 0.06). Median follow-up
was 43 months. The five-year local recurrence rates (5-year LR) were 1.1% for
mastectomy patients and 1.9% for BCT patients. CONCLUSIONS: Breast cancer
patients with margins of excision <2 mm have a substantial risk of residual
disease but the rates far exceed LR rates. These findings suggest that using
residual disease rates to determine the appropriate margin width is not reliable,
but also serve as a note of caution to track LR rates as institutions conform to
new national guidelines for margin management.
PMID- 25845614
TI - Development and microstructure of tooth histotypes in the blue shark, Prionace
glauca (Carcharhiniformes: Carcharhinidae) and the great white shark, Carcharodon
carcharias (Lamniformes: Lamnidae).
AB - Elasmobranchs exhibit two distinct arrangements of mineralized tissues in the
teeth that are known as orthodont and osteodont histotypes. Traditionally, it has
been said that orthodont teeth maintain a pulp cavity throughout tooth
development whereas osteodont teeth are filled with osteodentine and lack a pulp
cavity when fully developed. We used light microscopy, scanning electron
microscopy, and high-resolution micro-computed tomography to compare the
structure and development of elasmobranch teeth representing the two histotypes.
As an example of the orthodont histotype, we studied teeth of the blue shark,
Prionace glauca (Carcharhiniformes: Carcharhinidae). For the osteodont histotype,
we studied teeth of the great white shark, Carcharodon carcharias (Lamniformes:
Lamnidae). We document similarities and differences in tooth development and the
microstructure of tissues in these two species and review the history of
definitions and interpretations of elasmobranch tooth histotypes. We discuss a
possible correlation between tooth histotype and tooth replacement and review the
history of histotype differentiation in sharks. We find that contrary to a long
held misconception, there is no orthodentine in the osteodont teeth of C.
carcharias.
PMID- 25845615
TI - Concurrent administration of sexual assault prevention and risk reduction
programming: outcomes for women.
AB - The present study describes the 4- and 7-month postintervention outcomes of a
sexual assault risk reduction program for women, which was part of an evaluation
that included a prevention program for men. Relative to the control group,
participants evidenced more relational sexual assertiveness and self-protective
behavior, and were more likely to indicate that they utilized active verbal and
physical self-defense strategies. Whether or not women experienced subsequent
victimization did not differ between groups. Relative to control group women who
were victimized, program participants who were victimized between the 4- and 7
month follow-up blamed the perpetrator more and evidenced less self-blame.
PMID- 25845616
TI - The struggle to address woman battering in Slovakia: stories from service
providers.
AB - Following the fall of communism, Slovakia found itself in a challenging position:
to openly acknowledge the existence of intimate partner violence (IPV) and its
disproportionate effect on women and children without an infrastructure to
address victim safety, and provide resources and legal help. With collaboration
with non-governmental organizations (NGOs), the government responded by
developing shelters and introducing legislation that criminalized IPV and created
social services for victims. To assess implementation efforts, we conducted in
depth interviews with governmental officials and NGO personnel who provide
services for battered women. We focus on the operation and efficacy of shelters
to discover what services are most needed for battered women, the criminal
justice system's response to IPV, and what long-range goals will facilitate more
permanent solutions to the social problem of violence against women in Slovakia.
PMID- 25845617
TI - Community economic status and intimate partner violence against women in
bangladesh: compositional or contextual effects?
AB - In this research, we used a multi-level contextual-effects analysis to
disentangle the household- and community-level associations between income and
intimate partner violence (IPV) against women in Bangladesh. Our analyses of data
from 2,668 women interviewed as part of the World Health Organization (WHO) multi
country study on women's health and domestic violence against women showed that
household income was negatively associated with women's risk of experiencing IPV.
Controlling for residence in a low-income household, living in a low-income
community was not associated with women's risk of experiencing IPV. These results
support a household-level, not community-level, relationship between income and
IPV in Bangladesh.
PMID- 25845618
TI - Qualitative point-of-care D-dimer testing compared with quantitative D-dimer
testing in excluding pulmonary embolism in primary care.
AB - BACKGROUND: General practitioners can safely exclude pulmonary embolism (PE) by
using the Wells PE rule combined with D-dimer testing. OBJECTIVE: To compare the
accuracy of a strategy using the Wells rule combined with either a qualitative
point-of-care (POC) D-dimer test performed in primary care or a quantitative
laboratory-based D-dimer test. METHODS: We used data from a prospective cohort
study including 598 adults suspected of PE in primary care in the Netherlands.
General practitioners scored the Wells rule and carried out a qualitative POC
test. All patients were referred to hospital for reference testing. We obtained
quantitative D-dimer test results as performed in hospital laboratories. The
primary outcome was the prevalence of venous thromboembolism in low-risk
patients. RESULTS: Prevalence of PE was 12.2%. POC D-dimer test results were
available in 582 patients (97%). Quantitative test results were available in 401
patients (67%). We imputed results in 197 patients. The quantitative test and POC
test missed one (0.4%) and four patients (1.5%), respectively, with a negative
strategy (Wells <= 4 points and D-dimer test negative) (P = 0.20). The POC test
could exclude 23 more patients (4%) (P = 0.05). The sensitivity and specificity
of the Wells rule combined with a POC test were 94.5% and 51.0% and, combined
with a quantitative test, 98.6% and 47.2%, respectively. CONCLUSIONS: Combined
with the Wells PE rule, both tests are safe to use in excluding PE. The
quantitative test seemed to be safer than the POC test, albeit not statistically
significant. The specificity of the POC test was higher, resulting in more
patients in whom PE could be excluded.
PMID- 25845619
TI - Chemokine CX3CL1 and its receptor CX3CR1 are associated with human
atherosclerotic lesion volnerability.
AB - BACKGROUND: CX3CL1 and its receptor CX3CR1 have been emphasized in
atherosclerosis recently. In this study we investigated the role of the
chemokines CX3CL1 and their receptor CX3CR1 in atherogenesis and identified
whether the genetic variations in CX3CL1 and CX3CR1 impacted the atherosclerosis
process in coronary artery disease (CAD) or not. METHODS: CX3CL1/CX3CR1
expression in coronary and carotid artery specimens were analysed by
immunohistochemistry. CX3CR1 expression on CD4(+) CD28(-) T cells was analysed by
flow cytometry. We also screened for CX3CL1/CX3CR1 sequence variations selected
from the hapmap database and examined the association between CX3CL1/CX3CR1 and
CAD in the Chinese Han population. RESULTS: Immunohistochemical staining of
tissue from CAD patients showed increased CX3CL1/CX3CR1 expression in
atherosclerotic coronary and carotid artery plaques compared with normal
arteries. CX3CL1/CX3CR1 expression was correlated with the severity of the
atherosclerosis lesion. Patients with CAD also showed an increased number of
CX3CR1(+) CD4(+) CD28(-) T cells. Compared with their corresponding wild-type
genotypes, CX3CL1 rs170364 and CX3CR1 rs17793056 were associated with increased
susceptibility to CAD. CONCLUSIONS: CX3CL1 and CX3CR1 may contribute to the
formation of coronary atherosclerotic plaque in CAD.CX3CL1 rs170364 and CX3CR1
rs17793056 polymorphisms may be independent genetic risk factors for CAD.
PMID- 25845620
TI - Surviving the heat: heterogeneity of response in Saccharomyces cerevisiae
provides insight into thermal damage to the membrane.
AB - Environmental heat stress impacts on the physiology and viability of microbial
cells with concomitant implications for microbial activity and diversity.
Previously, it has been demonstrated that gradual heating of Saccharomyces
cerevisiae induces a degree of thermal resistance, whereas a heat shock results
in a high level of cell death. Here, we show that the impact of exogenous
nutrients on acquisition of thermal resistance differs between strains. Using
single-cell methods, we demonstrate the extent of heterogeneity of the heat
stress response within populations of yeast cells and the presence of
subpopulations that are reversibly damaged by heat stress. Such cells represent
potential for recovery of entire populations once stresses are removed. The
results show that plasma membrane permeability and potential are key factors
involved in cell survival, but thermal resistance is not related to homeoviscous
adaptation of the plasma membrane. These results have implications for growth and
regrowth of populations experiencing environmental heat stress and our
understanding of impacts at the level of the single cell. Given the important
role of microbes in biofuel production and bioremediation, a thorough
understanding of the impact of stress responses of populations and individuals is
highly desirable.
PMID- 25845621
TI - Incarceration and injection drug use in Baltimore, Maryland.
AB - AIMS: There is limited longitudinal research examining incarceration and
subsequent changes in drug use among people who inject drugs (PWID) in the United
States. The objective of the current study was to characterize the frequency of
incarceration and estimate the association between incarceration and subsequent
injection drug use among current and former PWIDs in one US city. DESIGN: ALIVE
(AIDS Linked to the Intravenous Experience) is a prospective cohort study of
current and former PWIDs, with semi-annual follow-up occurring since 1988.
SETTING: Baltimore, Maryland, USA. PARTICIPANTS: A total of 3245 participants
with 48 738 study visits were included. Participants enrolled from 1988 to 2012
with a median of 13 follow-up visits per participant (Interquartile range = 7
25). MEASUREMENTS: Incarcerations were defined as any self-reported jail or
prison stays in the previous 6 months that were >=7 days or longer. The primary
outcome was defined as any self-reported injection drug use in the previous 6
months. FINDINGS: At baseline, 29% were female, 90% African American and 33% HIV
positive. Fifty-seven per cent of participants experienced at least one
incarceration episode. After adjusting for confounders, there was a positive
association between incarceration and subsequent injection drug use [adjusted
odds ratio (AOR) = 1.48, 95% confidence interval (CI) = 1.37-1.59]; however,
stratified analysis showed that the effect was restricted to those who were not
injecting at the time of incarceration (AOR = 2.11, 95% CI = 1.88-2.37).
CONCLUSIONS: In the United States, incarceration of people who had previously
stopped injecting drugs appears to be associated with an increased risk of
subsequent injecting.
PMID- 25845622
TI - Emergency peripartum hysterectomy: results from the prospective Nordic Obstetric
Surveillance Study (NOSS).
AB - OBJECTIVE: To assess the prevalence and risk factors of emergency peripartum
hysterectomy. DESIGN: Nordic collaborative study. POPULATION: 605 362 deliveries
across the five Nordic countries. METHODS: We collected data prospectively from
patients undergoing emergency peripartum hysterectomy within 7 days of delivery
from medical birth registers and hospital discharge registers. Control
populations consisted of all other women delivering on the same units during the
same time period. MAIN OUTCOME MEASURES: Emergency peripartum hysterectomy rate.
RESULTS: The total number of emergency peripartum hysterectomies reached 211,
yielding an incidence rate of 3.5/10 000 (95% confidence interval 3.0-4.0)
births. Finland had the highest prevalence (5.1) and Norway the lowest (2.9).
Primary indications included an abnormally invasive placenta (n = 91, 43.1%),
atonic bleeding (n = 69, 32.7%), uterine rupture (n = 31, 14.7%), other bleeding
disorders (n = 12, 5.7%), and other indications (n = 8, 3.8%). The delivery mode
was cesarean section in nearly 80% of cases. Previous cesarean section was
reported in 45% of women. Both preterm and post-term birth increased the risk for
emergency peripartum hysterectomy. The number of stillbirths was substantially
high (70/1000), but the case fatality rate stood at 0.47% (one death, maternal
mortality rate 0.17/100 000 deliveries). CONCLUSIONS: A combination of
prospective data collected from clinicians and information gathered from register
based databases can yield valuable data, improving the registration accuracy for
rare, near-miss cases. However, proper and uniform clinical guidelines for the
use of well-defined international diagnostic codes are still needed.
PMID- 25845623
TI - A recombinant rabies virus expressing a phosphoprotein-eGFP fusion is rescued and
applied to the rapid virus neutralization antibody assay.
AB - Rabies remains a worldwide concern, and dogs are a major vector for rabies virus
(RABV) transmission. Vaccination is used in China to control the spread of rabies
in dogs, a practice which necessitates effective, efficient, and high-throughput
methods to confirm vaccination. The current rapid fluorescent focus inhibition
test (RFFIT) method to measure virus-neutralizing antibody titers in the serum
involves multiple steps, and more efficient methods are needed to match the
increasing demand for this type of monitoring. In this study, based on the
parental rRC-HL strain, a recombinant RABV rRV-eGFP expressing enhanced green
fluorescent protein (eGFP) fused with RABV P protein was generated by a reverse
genetic technique. The rRV-eGFP grew stably and successfully expressed P-eGFP
fusion in Neuro-2A (NA) host cells. Furthermore, the P protein was shown to co
localize with eGFP in rRV-eGFP-infected NA cells. Since eGFP is easily detected
in infected cells under a fluorescence microscope, rRV-eGFP could be used to
establish a more rapid virus-neutralizing antibody titers assay based on RFFIT,
designated as the RFFIT-eGFP method. From 69 canine serum samples, the RFFIT-eGFP
method was shown to be as specific and as sensitive as the RFFIT method,
suggesting that it might represent a faster tool than conventional RFFIT for
measuring RABV virus-neutralizing antibody titers in canine sera without
sacrificing accuracy.
PMID- 25845624
TI - Development of an immunochromatographic strip test for rapid detection of lily
symptomless virus.
AB - A rapid immunochromatographic strip (ICS) test for specific detection of lily
symptomless virus (LSV) was developed. The test is based on a double-antibody
sandwich format and employs two distinct anti-LSV polyclonal antibodies (IgG1 and
IgG2). The first antibody, IgG1 was used as the detection antibody conjugated to
colloidal gold and the second antibody, IgG2 was used to as the capture antibody
at the test line. The performance of the ICS test was evaluated and the results
obtained were compared with a quadruplex RT-PCR assay. When serial dilutions of
purified LSV were tested, the LSV detection limit of the ICS test was 6.0 * 10(
8)mg/mL, which was the same as the quadruplex RT-PCR assay. Relative to
quadruplex RT-PCR, the specificity and sensitivity of the ICS were 98.6% and
100%, respectively for field leaf samples. There was significant agreement
between the results of the ICS and quadruplex RT-PCR tests (kappa = 0.983).
Compared with conventional lily virus detection methods, our ICS test has many
advantages: simple, fast, low cost, high sensitivity and specificity, and has
applications in the laboratory and in the field to detect and control LSV.
PMID- 25845625
TI - Prediction of human clearance based on animal data and molecular properties.
AB - Human clearance is often predicted prior to clinical study from in vivo
preclinical data by virtue of interspecies allometric scaling methods. The aims
of this study were to determine the important molecular descriptors for the
extrapolation of animal data to human clearance and further to build a model to
predict human clearance by combination of animal data and the selected molecular
descriptors. These important molecular descriptors selected by genetic algorithm
(GA) were from five classes: quantum mechanical, shadow indices, E-state keys,
molecular properties, and molecular property counts. Although the data set
contained many outliers determined by the conventional Mahmood method, the
variation of most outliers was reduced significantly by our final support vector
machine (SVM) model. The values of cross-validated correlation coefficient and
root-mean-squared error (RMSE) for leave-one-out cross-validation (LOOCV) of the
final SVM model were 0.783 and 0.305, respectively. Meanwhile, the reliability
and consistency of the final model were also validated by an external test set.
In conclusion, the SVM model based on the molecular descriptors selected by GA
and animal data achieved better prediction performance than the Mahmood method.
This approach can be applied as an improved interspecies allometric scaling
method in drug research and development.
PMID- 25845626
TI - How and why neural and motor variation are related.
AB - Movements are variable. Recent findings in smooth pursuit eye movements provide
an explanation for motor variation in terms of the organization of the brain's
sensory-motor pathways. Variation in sensory estimation is propagated through
sensory-motor circuits and ultimately causes motor variation. The sensory origin
of motor variation creates trial-by-trial correlations among the responses of
neurons at each level of the sensory motor circuit, and between neural and
behavioral responses. We suggest that motor variation is a compromise between
multiple competing constraints. The brain strives for motor behavior that is
'good enough' in the face of constraints that tend to promote variation.
PMID- 25845627
TI - C. elegans locomotion: small circuits, complex functions.
AB - With 302 neurons in the adult Caenorhabditis elegans nervous system, it should be
possible to build models of complex behaviors spanning sensory input to motor
output. The logic of the motor circuit is an essential component of such models.
Advances in physiological, anatomical, and neurogenetic analysis are revealing a
surprisingly complex signaling network in the worm's small motor circuit. We are
progressing towards a systems level dissection of the network of premotor
interneurons, motor neurons, and muscle cells that move the animal forward and
backward in its environment.
PMID- 25845629
TI - Drug release from an oromucosal paste for the selective decontamination of the
oropharynx (in ICU patients and healthy volunteers).
AB - Selective oropharyngeal decontamination (SOD) is used in many ICUs in the
Netherlands and some other European countries. While its clinical effect has been
studied intensively, no studies have been done to assess the biopharmaceutical
aspects of the paste, i.e. it is not known which local concentrations exist. For
this study, five healthy volunteers were subjected to 400mg of the generally used
paste. Ten ICU patients were treated according to the normal standard in the ICU
of the University Medical Center Utrecht. Salivary levels of the various
substances were measured over time using two separate analytical methods. Also
the microbial burden of the oropharynx was assessed. The results show significant
variation in release, both ICU patients and healthy volunteers. The
antimicrobials tobramycin and colistin showed a relatively fast release, while
nystatin exhibited a controlled release-like pattern. Amphotericin B is hardly
released from the formulation. The concentration of the antimicrobial agents drop
to sub-MIC levels relatively fast. From a biopharmaceutical perspective,
amphotericin B should be replaced by nystatin. The application of the mouth paste
is subject to massive variation in daily practice; each nurse applies a different
amount, in a different way. In addition, the formulation is hard to apply and
unpleasant with regards to the taste and feel for the conscious patients. This is
not a clinical study, but a study that aimed to give a biopharmaceutical
justification for SOD Both the clinical practice and the clinically determined
levels of drugs enable critical evaluation of the outcome of clinical studies
performed until now.
PMID- 25845628
TI - 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate
vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers.
AB - Memory B cells are long-lived and could contribute to persistence of humoral
immunity by maintaining the plasma-cell pool or making recall responses upon re
exposure to an antigen. We determined the ability of a pneumococcal conjugate
vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells
against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and
23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35
children aged 12-23 months who received pneumococcal non-typeable Haemophilus
influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between
plasma antibodies and memory B cell frequencies were also assessed. After two
doses of PHiD-CV, the proportion of subjects with detectable memory B cells
against pneumococcal capsular polysaccharides increased significantly for
serotypes 1 (3-45%; P < 0.01), 19F (21-66%; P < 0.01) and 23F (13-36%; P = 0.02),
but not serotypes 6B (24-42%; P = 0.24) and 14 (21-40%; P = 0.06). Correlations
between antibodies and memory B cells were weak. Carriage of serotype 19F at
enrolment was associated with poor memory B cell responses against this serotype
at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P <
0.01; day 210: non-carriers, 72% versus carriers, 33%, P = 0.07). PHiD-CV is
capable of inducing memory B cells against some of the component pneumococcal
capsular polysaccharides.
PMID- 25845630
TI - N-stearoyltyrosine dipotassium ameliorates high-fat diet-induced obesity in
C57BL/6 mice.
AB - N-stearoyltyrosine dipotassium (NST-2K) as a neuroprotective candidate is
currently in preclinical studies in China. This study investigated the anti-obese
effect of NST-2K in high-fat diet-induced obese (DIO) mice. The DIO mice were
induced from male C57BL/6 mice by feeding high-fat diet for 11-weeks and treated
orally with NST-2K for other 4 weeks. The treatments of DIO mice with NST-2K at
60 or 100 mg/kg/day suppressed the body weight gain, decreased both visceral fat
weight and adipocyte size without influence on food intake. To evaluate the
effect of NST-2K on lipid metabolism, lipid parameters and several key molecules
in the plasma, liver, duodenum mucosa and adipose tissue were analyzed. NST-2K
ameliorated the low-grade inflammation in liver, inhibited pancreatic lipase
activity in duodenum mucosa, activated beta-oxidation system and reduced
lipogenesis, thus suppressed lipid accumulation in the liver, reduced adipocyte
size and improved lipid and carbohydrate metabolism. Overall, without influence
on food intake, NST-2K ameliorated high-fat diet-induced obesity via suppressing
liver inflammation, inhibiting dietary fat absorption, promoting lipolysis and
reducing lipogenesis.
PMID- 25845631
TI - Development of a simple, biocompatible and cost-effective Inulin
Diethylenetriamine based siRNA delivery system.
AB - Small interfering RNAs (siRNAs) have the potential to be of therapeutic value for
many human diseases. So far, however, a serious obstacle to their therapeutic use
is represented by the absence of appropriate delivery systems able to protect
them from degradation and to allow an efficient cellular uptake. In this work we
developed a siRNA delivery system based on inulin (Inu), an abundant and natural
polysaccharide. Inu was functionalized via the conjugation with
diethylenetriamine (DETA) residues to form the complex Inu-DETA. We studied the
size, surface charge and the shape of the Inu-DETA/siRNA complexes; additionally,
the cytotoxicity, the silencing efficacy and the cell uptake-mechanisms were
studied in the human bronchial epithelial cells (16HBE) and in the hepatocellular
carcinoma derived cells (JHH6). The results presented here indicate that Inu-DETA
copolymers can effectively bind siRNAs, are highly cytocompatible and, in JHH6,
can effectively deliver functional siRNAs. Optimal delivery is observed using a
weight ratio Inu-DETA/siRNA of 4 that corresponds to polyplexes with an average
size of 600nm and a slightly negative surface charge. Moreover, the uptake and
trafficking mechanisms, mainly based on micropinocytosis and clatrin mediated
endocytosis, allow the homogeneous diffusion of siRNA within the cytoplasm of
JHH6. Notably, in 16 HBE where the trafficking mechanism (caveolae mediated
endocytosis) does not allow an even distribution of siRNA within the cell
cytoplasm, no significant siRNA activity is observed. In conclusion, we developed
a novel inulin-based siRNA delivery system able to efficiently release siRNA in
JHH6 with negligible cytotoxicity thus opening the way for further testing in
more complex in vivo models.
PMID- 25845632
TI - Design and evaluation of a specific, bi-phase extended release system based on
differently coated mini-tablets.
AB - Mini-tablets are gaining great attention as systems capable of being formulated
into multiple unit systems providing a specific drug release pattern. Within the
presented research a combined, multiple-unit system, based on different coated
matrix mini-tablets, has been developed in order to achieve 24-h specific sigmoid
extended release of the model drug paliperidone. The mini-tablets were based on
different amounts of polyvinyl acetate/polyvinyl pyrolidone mixture as the matrix
former, providing extended release, and two different types of pH-dependent,
acrylic polymer coatings, providing delay in release onset, and thus achieving
the required specific sigmoid release pattern imposed by the original drug on the
market. The selected formulation proved to be consistent with pharmacopoeial
requirements. It was also in vitro similar (f2) to the original drug and the
theoretical linear release profile, as well as robust and reproducible regarding
in vitro release in different fasted gastro-intestinal conditions. This is proof
of concept that 24-h, specific, and almost linear release profile of drugs with
high solubility can be achieved by employing technology of coated matrix mini
tablets.
PMID- 25845633
TI - Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for
improved dissolution and oral bioavailability: In vitro and in vivo evaluation.
AB - The current study was aimed to investigate the potential of solid self
nanoemulsifying drug delivery system (S-SNEDDS) composed of Capmul MCM C8 (oil),
Tween 80 (surfactant) and Transcutol P (co-surfactant) in improving the
dissolution and oral bioavailability of darunavir. Liquid self-nanoemulsifying
drug delivery systems (L-SNEDDS) were developed by using rational blends of
components with good solubilizing ability for darunavir which were selected based
on solubility studies, further ternary phase diagram was constructed to determine
the self-emulsifying region. The prepared L-SNEDDS formulations were evaluated to
determine the effect of composition on physicochemical parameters like rate of
emulsification, clarity, phase separation, thermodynamic stability, cloud point
temperature, globule size and zeta potential. In vitro drug release studies
showed initial rapid release of about 13.3 +/- 1.4% within 30 min from L-SNEDDS
followed by slow continuous release of entrapped drug and reached a maximum of
62.6 +/- 3.5% release at the end of 24h. The globule size analysis revealed the
formation of nanoemulsion (144 +/- 2.3 nm) from the optimized L-SNEDDS
formulation and was physically adsorbed onto neusilin US2. In vitro dissolution
studies indicated faster dissolution of darunavir from the developed S-SNEDDS
with 3 times greater mean dissolution rate (MDR) compared to pure darunavir.
Solid state studies concluded the presence of drug in non-crystalline amorphous
state without any significant interaction of drug with the components of S
SNEDDS. Furthermore, in vivo pharmacokinetic studies in Wistar rats resulted in
enhanced values of peak drug concentration (Cmax) for L-SNEDDS (2.98 +/- 0.19
MUg/mL) and S-SNEDDS (3.7 +/- 0.28 MUg/mL) compared to pure darunavir (1.57 +/-
0.17 MUg/mL).
PMID- 25845635
TI - Practice variation in PEG tube placement: trends and predictors among providers
in the United States.
AB - BACKGROUND: Enteral access placement is performed among a variety of providers
and specialties, yet there is a dearth of literature on trends and factors
related to enteral access placement in the United States. OBJECTIVE: To examine
trends in the incidence of enteral access procedures performed by
gastroenterologists in the United States. DESIGN: Retrospective review of upper
endoscopic procedures that involved PEG tube placement between 2000 and 2010.
SETTING: Endoscopy sites participating in the Clinical Outcomes Research
Initiative (CORI). PATIENTS: Patients undergoing upper endoscopy. INTERVENTIONS:
PEG tube placement. MAIN OUTCOME MEASUREMENTS: Number of PEG tubes placed.
RESULTS: Overall PEG tube placement by a provider from 2000 to 2010 was 1.7%
(number of PEG tubes performed/number of upper endoscopies performed), with the
majority of them being performed by gastroenterologists. Very young and very old,
non-white racial background (Hispanic: odds ratio [OR] 1.21; 95% CI, 1.13-1.28;
black: OR 2.24; 95% CI, 2.12-2.36), and men (OR 1.44; 95% CI, 1.39-1.50) were
patient characteristics associated with greater PEG tube placement. In terms of
practice setting, PEG tube placement occurred more frequently in community and/or
health maintenance organization environments and on the East Coast. With respect
to provider characteristics, male providers were less likely than female
providers to perform a PEG tube insertion (OR 0.67; 95% CI, 0.64-0.71), and there
was a trend that as providers were further out of medical school they were less
likely to perform a PEG tube procedure. Interestingly, surgeons (OR 6.69; 95% CI,
6.18-7.24) and other providers (non-pediatric/non-general practice) (OR 3.22; 95%
CI, 2.63-3.94) were more likely to perform PEG tube procedures than were
gastroenterologists. LIMITATIONS: Participation in CORI is voluntary and may not
capture data on non-gastroenterologist providers. CONCLUSION: Significant
practice variation was noted in PEG tube placement in the United States with
respect to patient and provider characteristics, geographic region, and endoscopy
settings.
PMID- 25845636
TI - Gender differences in symptoms of hypothyroidism: a population-based DanThyr
study.
AB - OBJECTIVES: We examined the gender-specific symptom prevalences in hypothyroidism
and in healthy controls and explored the extent to which symptoms indicative of
thyroid status may be different in women and men. DESIGN AND METHODS: Patients
newly diagnosed with overt autoimmune hypothyroidism (n = 140) and controls free
of thyroid disease (n = 560) recruited from the same population participated in a
population-based study of The Danish Investigation of Iodine Intake and Thyroid
Diseases (DanThyr). Participants underwent a comprehensive programme including
blood tests and completion of questionnaires. The gender-specific distribution of
13 hypothyroidism-associated symptoms and a simple combined score (0-13) was
explored in conditional uni- and multivariate models taking into account a broad
spectrum of possible confounders. Diagnostic odds ratios (DORs) were calculated
as measures for the association between participant status (case vs control) and
presence of symptoms (yes vs no). RESULTS: In overt autoimmune hypothyroidism,
94.9% of women and 91.3% of men (P = 0.62) reported at least one of the
hypothyroidism-associated symptoms, with tiredness as the most common symptom
followed by dry skin and shortness of breath. In contrast, women free of thyroid
disease self-reported at least one hypothyroidism-associated symptom considerably
more often than men (73.7% vs 51.1%, P < 0.001). DORs (+/-SEM) for 0-1/2-3/4-13
symptoms were 0.07 (0.04-0.10)/2.15 (1.57-2.94)/7.99 (6.15-10.4) in men and 0.21
(0.16-0.28)/0.62 (0.58-0.66)/1.99 (1.90-2.09) in women. CONCLUSION: The presence
of symptoms is more indicative for overt autoimmune hypothyroidism in men than in
women, and presumably persistent symptoms after therapy of hypothyroidism will be
more common in women.
PMID- 25845637
TI - Relative stiffness of 3 bandage/splint constructs for stabilization of equine
midmetacarpal fractures.
AB - OBJECTIVE: Determine the relative stiffness of 3 bandage/splint constructs
intended for emergency fracture stabilization. DESIGN: Experimental model. A
single plane free end deflection model was developed to simulate the forces
placed on a bandage/splint construct during stabilization of a complete mid
metacarpal bone fracture. The total deflection of the model in one plane was
measured following application of 3 different bandage/splint combinations
including a classic, 3 layered Robert Jones Bandage (RJB) with a splint placed on
the outside of the bandage (RJB-3), an RJB with splint placed after the first of
3 bandage layers (RJB-1), and a single layer full limb bandage with external
splint (SS). Comparisons were made between the deflections of the model with each
bandage/splint combinations in an effort to determine the most effective method
for field fracture stabilization. SETTING: Laboratory. ANIMALS: No animals were
utilized in data collection for this study. Two live horses were utilized during
the pilot study. INTERVENTIONS: Application of bandage and splint to a model
intended to simulate the bending force on a lower forelimb fracture in a horse
MEASUREMENTS AND MAIN RESULTS: Deflection was determined by the difference
between the height of the model's supported free end before application of a 4.5
kg weight and at the conclusion of the deflection test. There was no significant
difference in the amount of deflection between bandage/splint combinations (78 +/
32 mm (RJB-1), 94 +/- 44 mm (RJB-3), and 93 +/- 33 mm (SS)) CONCLUSIONS: The one
layer bandage with splint was equivalent to either RJB configuration in the mean
amount of deflection in the simple model of a fracture.
PMID- 25845638
TI - Angelica sinensis polysaccharides inhibit endothelial progenitor cell senescence
through the reduction of oxidative stress and activation of the Akt/hTERT
pathway.
AB - CONTEXT: Angelica sinensis (Oliv.) Diels (Apiaceae) polysaccharides (ASP) may
play a key role in anti-ischemic activity. However, the anti-atherosclerotic
activity and mechanism are unknown. OBJECTIVE: This study investigated the
protective effects of ASP against ox-LDL-induced senescence of EPCs and explored
its underlying molecular mechanisms. MATERIALS AND METHODS: Mononuclear cells
were isolated from bone marrow (BM) of SD rats and differentiated to EPCs. EPCs
were exposed to oxidized low-density lipoprotein (ox-LDL, 10 ug/mL, 24 h) and
incubated with or without high-dose (100 ug/mL, 48 h) or low-dose (20 ug/mL, 48
h) ASP. Another group of EPCs was pre-treated with Wortmannin (100 nM, 45 min), a
PI3K/Akt inhibitor. EPC senescence, telomerase activity, and superoxide anion
levels were assessed using SA-beta-galactosidase staining, telomerase PCR-ELISA
analysis, and DHE staining, respectively. The expression of related proteins,
including Akt, p-Akt, hTERT, p-hTERT, and gp91phox, were detected using western
blot. RESULTS: EPCs (47.3%) were SA-beta-gal positive after treatment by ox-LDL,
additionally, ox-LDL significantly increased superoxide anion levels (375% versus
100%), and inhibited telomerase activity (42% versus 100%). However, the pro
senescent effect of ox-LDL was attenuated about three-fold (16.7%), superoxide
anion levels were decreased more than two-fold (148%), and telomerase activity
was recovered partly (88% versus 42%) in the EPCs when treated with ASP (100
ug/mL). The immunoblotting confirmed that ASP attenuated inhibition of
phosphorylation of Akt and hTERT induced by ox-LDL and down-regulated increased
the expression of gp91-phox. Moreover, some effects of ASP were partially
abrogated in the presence of Wortmannin. DISCUSSION: Ox-LDL induced senescence of
EPCs via inhibition of telomerase activity, which was influenced by oxidative
stress and the Akt/hTERT pathway. The inhibition of EPC senescence by ASP could
be important for potential therapeutics. CONCLUSION: Treatment of EPCs with ASP
remarkably attenuates the harmful effects of ox-LDL via augmentation of Akt/hTERT
phosphorylation and inhibition of oxidative stress.
PMID- 25845639
TI - Screening of antidepressant activity and estimation of quercetin from Coccinia
indica using TLC densitometry.
AB - CONTEXT: Coccinia indica Naud (Cucurbitaceae) has been traditionally used for the
treatment of depression but these claims have not been validated. OBJECTIVES: The
objective of this study is to investigate antidepressant activity of various
extracts and fractions of C. indica aerial parts, and to estimate content of
quercetin in the plant using TLC densitometry. MATERIALS AND METHODS: Coccinia
indica aerial parts were successively extracted using solvents in increasing
order of polarity, namely n-hexane, chloroform, methanol, and water. Various
extracts were evaluated for antidepressant activity at doses of 200 or 400 mg/kg,
p.o., upon acute administration in mice using the forced swim test (FST). The
bioactive extract was partitioned successively using solvents in increasing order
of polarity, namely n-hexane, ethyl acetate, and n-butanol. All fractions were
also screened for antidepressant activity at doses of 25 or 50 mg/kg, p.o., upon
acute administration in mice. RESULTS: The methanol extract significantly reduced
the duration of immobility in FST at dose of 400 mg/kg without affecting
locomotor activity in open field test, thus, confirmed its antidepressant
activity, which was statistically equivalent to the standard drug (imipramine, 15
mg/kg, i.p.). Ethyl acetate fraction (EAF) exhibited antidepressant activity at
50 mg/kg. Comparative TLC fingerprint studies confirmed the presence of quercetin
in methanol extract and EAF. Quercetin was used as a chemical marker to
standardize C. indica aerial parts using the validated TLC densitometric method,
and the content of quercetin was found to be 0.00172% w/w. CONCLUSIONS: The
present studies scientifically validated traditional claims of C. indica for
antidepressant activity.
PMID- 25845640
TI - Anticancer activities of Withania somnifera: Current research, formulations, and
future perspectives.
AB - CONTEXT: Cancer, being a cause of death for major fraction of population
worldwide, is one of the most studied diseases and is being investigated for the
development of new technologies and more accurate therapies. Still the currently
available therapies for cancer have many lacunae which affect the patient's
health severely in the form of side effects. The natural drugs obtained from the
medicinal plants provide a better alternative to fight against this devastating
disease. Withania somnifera L. Dunal (Solanaceae), a well-known Ayurvedic
medicinal plant, has been traditionally used to cure various ailments for
centuries. OBJECTIVES: Considering the immense potential of W. somnifera, this
review provides a detail account of its vital phytoconstituents and summarizes
the present status of the research carried out on its anticancerous activities,
giving future directions. METHODS: The sources of scientific literature were
accessed from various electronic databases such as PubMed, Google Scholar,
Science Direct, and library search. RESULTS: Various parts of W. somnifera
especially the roots with its unique contents have been proved effective against
different kinds of cancers. The most active components withanolides and
withaferins along with a few other metabolites including withanone (WN) and
withanosides have been reported effective against different types of cancer cell
lines. CONCLUSION: This herb holds an important place among various anticancer
medicinal plants. It is very essential to further screen and to investigate
different formulations for anticancer therapy in vitro as well as in vivo in
combination with established chemotherapy.
PMID- 25845641
TI - Chlorogenic acid-enriched extract from Eucommia ulmoides leaves inhibits hepatic
lipid accumulation through regulation of cholesterol metabolism in HepG2 cells.
AB - CONTEXT: Eucommia ulmoides Oliver (Eucommiaceae) leaf exhibits beneficial lipid
lowering and anti-obesity effects. However, the mechanisms remain unknown.
OBJECTIVE: The objective of this study is to investigate the lipid-lowering
effects of chlorogenic acid (CGA)-enriched extract from this plant (CAEF) in
human hepatoma HepG2 cells, focusing on cholesterol metabolism. MATERIALS AND
METHODS: HepG2 cells were treated with CAEF (10, 20, 25, 40, 60, and 80 mg/L),
CGA (0.3, 3, 30, 300, and 600 MUmol/L), and simvastatin (0.1, 1, 10, 50, and 100
MUmol/L) for 24 or 48 h. The cytotoxicity, Oil red O staining, total cholesterol,
and triacylglycerol in supernatants were determined. The mRNA expression of genes
involved in cholesterol metabolism was determined with RT-PCR. The protein
expression of HMG-CoA reductase (HMGCR) was examined by immunocytochemistry and
western-blot. RESULTS: The IC50 values were 59.2 mg/L for CAEF, 335.9 MUmol/L for
CGA, and 10.5 MUmol/L for simvastatin. By treating cells with CAEF (25 mg/L), CGA
(30 MUmol/L), or simvastatin (10 MUmol/L) for 48 h, the efflux of total
cholesterol and triacylglycerol was increased (CAEF, 4.06- and 31.00-folds; CGA,
2.94- and 2.17-folds; and simvastatin, 3.94- and 24.67-folds), and the cellular
lipid droplets were reduced in Oil red O staining. CAEF and CGA increased mRNA
expression of ABCA1, CYP7A1, and AMPKalpha2, while CAEF and simvastatin decreased
SREBP2. However, their effects on LXRalpha mRNA expression were variable.
Importantly, all drugs significantly inhibited protein expression of HMGCR at
mRNA and protein levels. DISCUSSION AND CONCLUSION: CAEF is a promising dietary
supplement to prevent obesity and dyslipidemia and the effects appear to be due,
at least in part, to regulating cholesterol metabolism through inhibition of
HMGCR in HepG2 cells.
PMID- 25845642
TI - T cell regulation by Phlomis lanata protein extracts in mice.
AB - CONTEXT: Phytopharmacology is a complex but very promising research area. The
different plant parts and extraction methods may result in opposed effects.
Phlomis species have been reported for both anti-inflammatory and tonic
properties. OBJECTIVE: The effect of Phlomis lanata Willd. (Lamiaceae) protein
extracts on immune cell reactivity was studied in the experimental mouse model.
MATERIALS AND METHODS: Protein extracts from P. lanata aerial parts were
fractionated by Q-sepharose ion-exchange chromatography and applied to whole
spleen cells or T-cell subsets at 5 MUg/ml. Cell growth and cytokine production
were evaluated after 4 and 2 d of culture using (3)H-thymidine-uptake and ELISA
techniques, respectively. RESULTS: Among the protein fractions tested, column
wash proteins (W1) and the fraction eluted using 600 mM NaCl (F6) reduced by 76%
and increased by 78% spleen cell proliferation, respectively. W1 suppressed
proliferation of effector T-cells, but stimulated the growth of
suppressor/regulatory cells by 62-148%. Although W1 stimulated IL-2 and IL-10
production from total spleen cells, it significantly increased IL-10 (50%) and
reduced IL-2 (30-50%) production from T-cells, while TNF-alpha release was
enhanced in CD25(+)CD4(+) by 92% and reduced by 50% in CD25(+)CD8(+) cells. F6
stimulated whole spleen cell growth, reduced proliferation of CD8(+) and CD25(+)
cells by approximately 50%, while decreasing by 60-80% TNF-alpha production from
CD25(-) and CD25(+)CD8(+) cells. DISCUSSION AND CONCLUSION: The suppressive
activity of W1 could be attributed to IL-10 and TNF-alpha, while the stimulatory
effect of F6 could be attributed to the inhibition of T-regulatory cells. In the
same plant, coexisting protein fractions induce both immunostimulatory and
immunosuppressive activities.
PMID- 25845643
TI - Compounds from Sedum caeruleum with antioxidant, anticholinesterase, and
antibacterial activities.
AB - CONTEXT: This is the first study on the phytochemistry, antioxidant,
anticholinesterase, and antibacterial activities of Sedum caeruleum L.
(Crassulaceae). OBJECTIVE: The objective of this study is to isolate the
secondary metabolites and determine the antioxidant, anticholinesterase, and
antibacterial activities of S. caeruleum. MATERIALS AND METHODS: Six compounds (1
6) were isolated from the extracts of S. caeruleum and elucidated using UV, 1D-,
2D-NMR, and MS techniques. Antioxidant activity was investigated using DPPH(*),
CUPRAC, and ferrous-ions chelating assays. Anticholinesterase activity was
determined against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)
enzymes using the Ellman method. Antibacterial activity was performed according
to disc diffusion and minimum inhibitory concentration (MIC) methods. RESULTS:
Isolated compounds were elucidated as ursolic acid (1), daucosterol (2), beta
sitosterol-3-O-beta-D-galactopyranoside (3), apigenin (4), apigetrin (5), and
apiin (6). The butanol extract exhibited highest antioxidant activity in all
tests (IC50 value: 28.35 +/- 1.22 ug/mL in DPPH assay, IC50 value: 40.83 +/- 2.24
ug/L in metal chelating activity, and IC50 value: 23.52 +/- 0.44 ug/L in CUPRAC),
and the highest BChE inhibitory activity (IC50 value: 36.89 +/- 0.15 ug/L).
Moreover, the chloroform extract mildly inhibited (MIC value: 80 ug/mL) the
growth of all the tested bacterial strains. DISCUSSION AND CONCLUSION: Ursolic
acid (1), daucosterol (2), beta-sitosterol-3-O-beta-D-galactopyranoside (3),
apigenin (4), apigetrin (5), and apiin (6) were isolated from Sedum caeruleum for
the first time. In addition, a correlation was observed between antioxidant and
anticholinesterase activities of bioactive ingredients of this plant.
PMID- 25845644
TI - Low-dose total-body irradiation and alemtuzumab-based reduced-intensity
conditioning regimen results in durable engraftment and correction of clinical
disease among children with chronic granulomatous disease.
AB - HSCT with MAC is associated with durable donor engraftment for patients with CGD;
however, MAC is limited by high rates of RRT. We used a novel RIC regimen with LD
TBI (200 cGy * two doses), fludarabine (30 mg/m(2) * three doses), and proximal
alemtuzumab (0.5 mg/kg/dose * one dose) and unrelated donor grafts for
consecutive patients with high-risk CGD who were not candidates for MAC at our
institution. Among four children with CGD transplanted at our institution, three
PBSC recipients are alive with sustained donor engraftment (median follow-up: two
yr) and resolution of pre-HSCT active infections while one patient with bone
marrow graft is alive after graft failure and autologous recovery. RIC may be a
curative option for children with high-risk CGD.
PMID- 25845645
TI - Performance of Frozen Density Embedding for Modeling Hole Transfer Reactions.
AB - We have carried out a thorough benchmark of the frozen density-embedding (FDE)
method for calculating hole transfer couplings. We have considered 10 exchange
correlation functionals, 3 nonadditive kinetic energy functionals, and 3 basis
sets. Overall, we conclude that with a 7% mean relative unsigned error, the PBE
and PW91 functionals coupled with the PW91k nonadditive kinetic energy functional
and a TZP basis set constitute the most stable and accurate levels of theory for
hole transfer coupling calculations. The FDE-ET method is found to be an
excellent tool for computing diabatic couplings for hole transfer reactions.
PMID- 25845646
TI - Role of Toll-like receptor 4 signaling in cutaneous chronic graft-versus-host
disease.
AB - Cutaneous damage is one of the characterized manifestations in chronic graft
versus-host disease (cGVHD). When local effective immunity in the skin is altered
to a dysimmune reaction, cutaneous injuries occur. Toll-like receptor 4 signaling
is regarded as a central mediator of inflammation and organ injury. In this
study, we found that TLR4 mRNA in peripheral blood from patients with cutaneous
cGVHD was markedly increased compared with that from non-GVHD patients and
healthy controls. In addition, NF-kappaB expression, TLR4 downstream signaling,
and TLR4-mediated cytokines, including IL-6 and ICAM-1, were upregulated.
Moreover, ICAM-1 was widely distributed in skin biopsies from patients with
cutaneous cGVHD. We also found that LPS induced TLR4-mediated NF-kappaB
activation and IL-6 and ICAM-1 secretion in human fibroblasts in vitro. Thus,
TLR4, NF-kappaB, IL-6, and ICAM-1 contribute to the inflammatory response that
occurs in cutaneous cGVHD, indicating the TLR4 pathway may be a novel target for
cutaneous cGVHD therapy.
PMID- 25845647
TI - Selective fusion in adolescent idiopathic scoliosis: a radiographic evaluation of
risk factors for imbalance.
AB - STUDY DESIGN: Retrospective database, chart and medical imaging review.
OBJECTIVES: To report on the outcome and evaluate possible risk factors for
postoperative complications following selective spinal fusion in patients with
adolescent idiopathic scoliosis (AIS). MATERIALS AND METHODS: All patients with
AIS who underwent either a selective thoracic or selective thoracolumbar/lumbar
spinal fusion at our institution from January 2001 to December 2011 inclusive
were included in this study. The minimum postoperative follow-up period of all
patients was 2 years. RESULTS: During the 11-year study period, 157 patients with
AIS underwent surgery for their progressive spinal deformity. Thirty patients (19
%) had a selective spinal fusion, with 16 patients (group A) having a selective
thoracic, and 14 patients (group B) having a selective thoracolumbar/lumbar
spinal arthrodesis. In both groups the main postoperative complications were
adding-on (25 % group A, 36 % group B) and coronal decompensation (25 % group A,
29 % group B). In group A, no statistically significant risk factors for
postoperative complications were identified. In group B, global coronal balance
was identified as a significant risk factor for adding-on. Patients with adding
on had significantly higher coronal balance scores (mean 3.6) than those who did
not experience adding-on (mean 1.9) (p = 0.03). In addition, those with adding-on
had a significantly smaller bending lumbar Cobb angle (mean 15) than those
without adding-on (mean 31.6) (p = 0.015). None of the patients who underwent
selective spinal fusion required revision surgery. CONCLUSION: Although the
complication rate after performing a selective spinal fusion is high, the
revision rate remains low and the debate whether or not to perform a selective
spinal fusion will continue.
PMID- 25845648
TI - Conscious Vision in Action.
AB - It is natural to assume that the fine-grained and highly accurate spatial
information present in visual experience is often used to guide our bodily
actions. Yet this assumption has been challenged by proponents of the Two Visual
Systems Hypothesis (TVSH), according to which visuomotor programming is the
responsibility of a "zombie" processing stream whose sources of bottom-up spatial
information are entirely non-conscious (Clark, 2007, 2009; Goodale & Milner,
1992, 2004a; Milner & Goodale, 1995/2006, 2008). In many formulations of TVSH,
the role of conscious vision in action is limited to "recognizing objects,
selecting targets for action, and determining what kinds of action, broadly
speaking, to perform" (Clark, 2007, p. 570). Our aim in this study is to show
that the available evidence not only fails to support this dichotomous view but
actually reveals a significant role for conscious vision in motor programming,
especially for actions that require deliberate attention.
PMID- 25845653
TI - Resveratrol prevents osteoporosis in ovariectomized rats by regulating microRNA
338-3p.
AB - Osteoporosis is a disease characterized by loss of bone mass and degeneration of
the microstructure of bone. Resveratrol (3,5,4-tri-hydroxystilbene; RESV) may
delay the onset of a variety of age-related diseases. In the present study, an
ovariectomized female rat model was used to detect the changes in microRNAs
(miRNAs/miRs) following RESV treatment. Subsequently, the target genes of miRNA
were predicted using TargetScan software and determined using a dual-luciferase
reporter assay. Finally, the role of miR-338-3p in the proliferation and
differentiation of human osteoblast (HOB) cells was confirmed. The predominant
finding of the present study was the identification of an intact mechanism of the
effect of RESV in osteoporosis treatment. The results suggested that RESV
suppresses miR-338-3p, followed by an increase in the expression of runt-related
transcription factor 2 in HOB cells.
PMID- 25845654
TI - Bevacizumab did not reduce the risk of anemia associated with chemotherapy: an up
to-date meta-analysis.
AB - PURPOSE: The risk of anemia due to bevacizumab-based chemotherapy has not been
well described, and new randomized controlled trials (RCTs) have been reported in
recent years. We therefore conducted an up-to-date meta-analysis of RCTs to fully
characterize the risk of anemia with bevacizumab. METHODS: We carried out an
electronic search of Medline, Embase, and The Cochrane Central Register of
Controlled Trials to investigate the effects of RCTs on bevacizumab treatment on
cancer patients up to October 2014, and random or fixed-effect meta-analytical
models were used to assess the risk ratio (RR) of anemia due to the use of
bevacizumab according to the heterogeneity of included studies. RESULTS: A total
of 13,173 patients were included in this analysis from 18 RCTs. Among those
patients receiving bevacizumab and chemotherapy, the incidences of all-grade and
high-grade (grade 3 and above) anemia were 24% (95% confidence interval (CI) 13
41%) and 4.0% (95% CI 3.0-6.0%), respectively. Bevacizumab-containing therapy did
not significantly decreased the risk of developing all-grade anemia (RR 0.872,
95% CI 0.739-1.029, P = 0.104) and high-grade anemia (RR 0.850, 95% CI 0.720
1.002, P = 0.053), which is not in agreement with previous meta-analysis. On
subgroup analysis, we did not find significant risk differences based on
bevacizumab dosage, tumor types, and concomitant drugs. When stratified by dose
level, a significantly decreased risk of high-grade anemia with bevacizumab was
obtained in a lower dose level (2.5 mg/kg/week, RR 0.773, 95% CI 0.611-0.978, P =
0.031) compared to control group. CONCLUSIONS: Bevacizumab did not significantly
reduce the risk of anemia with chemotherapy in cancer patients.
PMID- 25845655
TI - The impact of a changed legislation on reporting of adverse drug reactions in
Sweden, with focus on nurses' reporting.
AB - PURPOSE: In March 2007, a legislative amendment was issued in Sweden compelling
nurses to report all suspected adverse drug reactions (ADRs) to the national
pharmacovigilance system. The aims of this study were to describe the status of
ADR reporting, before and after the implementation of the legislative changes,
and to describe the general characteristics of suspected ADRs reported by nurses.
METHODS: The Swedish pharmacovigilance system during the study period constituted
six regional centres responsible for the handling of all spontaneous ADR reports
within their region. In this study, we identified all individual ADR reports from
2005 and 2010, analysed in depth the ADR reports from two regional centres and
collated information about the reporter and the nature of the reported ADR.
RESULTS: From the two regional centres, a total of 898 and 1074 reports were
submitted in 2005 and 2010 respectively. Nurses submitted 31% (275 reports) of
the reports in 2005 and 24% (260 reports) in 2010. Nurses' reporting of serious
ADRs was 3% (seven reports) in 2005 and 7% (17 reports) in 2010 with reporting of
unlabelled ADRs at 4% (11 reports) in 2005 and 17% (45 reports) in 2010. Most of
the serious and/or unlabelled reactions were related to vaccine administration
(14 reports in 2005 and 36 reports in 2010). CONCLUSIONS: The overall ADR
reporting by nurses did not appear to increase after the change in reporting
legislation. The proportion of serious and/or unlabelled ADRs reported by nurses
did however appear to increase during the same period. Taken together, our data
suggests that further pro-active measures should be considered in order to
involve nurses in the reporting of suspected ADRs.
PMID- 25845656
TI - Association between hypnotics use and increased mortality: causation or
confounding?
AB - PURPOSE: Many research studies have found associations between benzodiazepines
and/or z-hypnotics (BZZ) and increasing mortality, leading to a discussion about
causation or confounding. This study suggests a factor that could produce this
association through confounding. METHODS: The Norwegian population in 2010
supplied 8862 deaths ages 41-80 and 898,289 controls. Index dates were added to
control records which corresponded to death dates. BZZ use was recorded for 2
years before death/index date. RESULTS: Persons exposed to BZZ were more likely
(OR = 2.3) to die than those who were not. With proximity of death, increasingly
larger proportions of the prospective deaths received prescriptions for BZZ,
until in the last 2 months 40-45% received BZZ. The frequency of BZZ use in
controls increased with age as opposed to the death cohort where all ages showed
similar rates of BZZ use. In the last few months before death, the youngest age
group had an OR = 5.8 for BZZ use while the oldest age group an OR = 1.8,
adjusted for age and sex. Opioid use showed a similar pattern of increasing use
near death. CONCLUSIONS: The increased use of BZZ with approaching death is
consistent with increasing symptomatic treatment in terminal illness. Thus, the
association of BZZ and mortality is more likely to be due to confounding than to
causality. Further evidence from this and other research includes similar use
patterns for other drugs such as opioids, the lack of specificity in cause of
death and the size of the association regarding age and time to death.
PMID- 25845657
TI - Inter-individual variation in morphine clearance in children.
AB - OBJECTIVES: The aim of the study was to determine the extent of inter-individual
variation in clearance of intravenous morphine in children and to establish which
factors are responsible for this variation. METHODS: A systematic literature
review was performed to identify papers describing the clearance of morphine in
children. The following databases were searched: Medline, Embase, International
Pharmaceutical Abstracts, CINAHL, and Cochrane library. From the papers, the
range in plasma clearance and the coefficient of variation (CV) in plasma
clearance were determined. RESULTS: Twenty-eight studies were identified. After
quality assessment, 20 studies were included. Only 10 studies gave clearance
values for individual patients. The majority of the studies were in critically
ill patients. Inter-individual variability of morphine clearance was observed in
all age groups, but greatest in critically ill neonates (both preterm and term)
and infants. In critically ill patients, the CV was 16-97% in preterm neonates,
24-87% in term neonates, 35 and 134% in infants, 39 and 55% in children, and 74%
in adolescents. The CV was 37 and 44% respectively in non-critically ill neonates
and infants. The mean clearance was higher in children (32 and 52 ml min(-1) kg(
1)) than in neonates (2 to 16 ml min(-1) kg(-1)). CONCLUSIONS: Large inter
individual variation was seen in morphine clearance values in critically ill
neonates and infants.
PMID- 25845658
TI - Psychometric properties of the Five-Digit Test in patients with stroke.
AB - PURPOSE: To examine the ecological validity, predictive validity, and
responsiveness of the Five Digit Test (FDT) in patients with stroke. METHODS: We
included inpatients with stroke (n = 144, 114 and 105 in the ecological validity,
predictive validity, and responsiveness analysis, respectively) in the study. At
admission, the FDT and Barthel Index (BI) were assessed; at discharge, the FDT,
BI, Postural Assessment Scale for Stroke Patients (PASS), and Mobility Subscale
of the Stroke Rehabilitation Assessment of Movement (MO-STREAM) were assessed.
RESULTS: In the ecological validity analysis, the scores of the selective and
alternating attention indices of the FDT were moderately correlated with those of
the BI at admission and discharge (Spearman rho = -0.38 to -0.45). In the
predictive validity analysis, the scores of the two attention indices of the FDT
at admission were moderately correlated with the scores of the BI, PASS, and MO
STREAM at discharge (rho = -0.33 to -0.45). In the responsiveness analysis, the
two attention indices of the FDT between admission and discharge had large
differences (success rate difference = 0.56-0.67, Wilcoxon Z = -5.90 to -6.60).
CONCLUSION: Our results indicate that the selective and alternating attention
indices of the FDT have acceptable ecological validity, predictive validity, and
good responsiveness in patients with stroke. IMPLICATIONS FOR REHABILITATION: The
Five Digit Test (FDT), an efficient and culture-free assessment tool, has been
used to assess selective attention and alternating attention The selective index
and alternating attention index of the FDT showed acceptable ecological validity,
predictive validity, and good responsiveness in patients with stroke.
PMID- 25845659
TI - Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila
and Attenuate High-Fat Diet-Induced Metabolic Syndrome.
AB - Dietary polyphenols protect against metabolic syndrome, despite limited
absorption and digestion, raising questions about their mechanism of action. We
hypothesized that one mechanism may involve the gut microbiota. To test this
hypothesis, C57BL/6J mice were fed a high-fat diet (HFD) containing 1% Concord
grape polyphenols (GP). Relative to vehicle controls, GP attenuated several
effects of HFD feeding, including weight gain, adiposity, serum inflammatory
markers (tumor necrosis factor [TNF]alpha, interleukin [IL]-6, and
lipopolysaccharide), and glucose intolerance. GP lowered intestinal expression of
inflammatory markers (TNFalpha, IL-6, inducible nitric oxide synthase) and a gene
for glucose absorption (Glut2). GP increased intestinal expression of genes
involved in barrier function (occludin) and limiting triglyceride storage
(fasting-induced adipocyte factor). GP also increased intestinal gene expression
of proglucagon, a precursor of proteins that promote insulin production and gut
barrier integrity. 16S rRNA gene sequencing and quantitative PCR of cecal and
fecal samples demonstrated that GP dramatically increased the growth of
Akkermansia muciniphila and decreased the proportion of Firmicutes to
Bacteroidetes, consistent with prior reports that similar changes in microbial
community structure can protect from diet-induced obesity and metabolic disease.
These data suggest that GP act in the intestine to modify gut microbial community
structure, resulting in lower intestinal and systemic inflammation and improved
metabolic outcomes. The gut microbiota may thus provide the missing link in the
mechanism of action of poorly absorbed dietary polyphenols.
PMID- 25845660
TI - Rapid Repression of ADP Transport by Palmitoyl-CoA Is Attenuated by Exercise
Training in Humans: A Potential Mechanism to Decrease Oxidative Stress and
Improve Skeletal Muscle Insulin Signaling.
AB - Mitochondrial ADP transport may represent a convergence point unifying two
prominent working models for the development of insulin resistance, as reactive
lipids (specifically palmitoyl-CoA [P-CoA]) can inhibit ADP transport and
subsequently increase mitochondrial reactive oxygen species emissions. In the
current study, we aimed to determine if exercise training in humans diminished P
CoA attenuation of mitochondrial ADP respiratory sensitivity. Six weeks of
exercise training increased whole-body glucose homeostasis and skeletal muscle
Akt signaling and reduced markers of oxidative stress without reducing maximal
mitochondrial H2O2 emissions. To ascertain if enhanced mitochondrial ADP
transport contributed to the improvement in the in vivo oxidative state, we
determined mitochondrial ADP sensitivity in the presence and absence of P-CoA. In
the absence of P-CoA, exercise training reduced mitochondrial ADP sensitivity. In
contrast, exercise training increased mitochondrial ADP sensitivity with P-CoA
present. We further show that P-CoA noncompetitively inhibits mitochondrial ADP
transport and the ability of ADP to attenuate mitochondrial H2O2 emission.
Altogether, the current data provide a potential mechanism for how P-CoA
contributes to insulin resistance and highlight the ability of exercise training
to diminish P-CoA attenuation in mitochondrial ADP transport.
PMID- 25845661
TI - Metabolic Syndrome Abolishes Glucagon-Like Peptide 1 Receptor Agonist Stimulation
of SERCA in Coronary Smooth Muscle.
AB - Metabolic syndrome (MetS) doubles the risk of adverse cardiovascular events.
Glucagon-like peptide 1 (GLP-1) receptor agonists induce weight loss, increase
insulin secretion, and improve glucose tolerance. Studies in healthy animals
suggest cardioprotective properties of GLP-1 receptor agonists, perhaps partially
mediated by improved sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) activity.
We examined the acute effect of GLP-1 receptor agonists on coronary smooth muscle
cells (CSM) enzymatically isolated from lean, healthy Ossabaw miniature swine.
Intracellular Ca(2+) handling was interrogated with fura-2. The GLP-1 receptor
agonist exenatide activated SERCA but did not alter other Ca(2+) transporters.
Further, we tested the hypothesis that chronic, in vivo treatment with GLP-1
receptor agonist AC3174 would attenuate coronary artery disease (CAD) in swine
with MetS. MetS was induced in 20 swine by 6 months' feeding of a hypercaloric,
atherogenic diet. Swine were then randomized (n = 10/group) into placebo or
AC3174 treatment groups and continued the diet for an additional 6 months. AC3174
treatment attenuated weight gain, increased insulin secretion, and improved
glucose tolerance. Intravascular ultrasound and histology showed no effect of
AC3174 on CAD. MetS abolished SERCA activation by GLP-1 receptor agonists. We
conclude that MetS confers vascular resistance to GLP-1 receptor agonists,
partially through impaired cellular signaling steps involving SERCA.
PMID- 25845663
TI - Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a
Diet-Induced Type 2 Diabetes Model.
AB - Understanding the molecular networks controlling ectopic lipid deposition,
glucose tolerance, and insulin sensitivity is essential to identifying new
pharmacological approaches to treat type 2 diabetes. We recently identified
serine/threonine protein kinase 25 (STK25) as a negative regulator of glucose and
insulin homeostasis based on observations in myoblasts with acute depletion of
STK25 and in STK25-overexpressing transgenic mice. Here, we challenged Stk25
knockout mice and wild-type littermates with a high-fat diet and showed that
STK25 deficiency suppressed development of hyperglycemia and hyperinsulinemia,
improved systemic glucose tolerance, reduced hepatic gluconeogenesis, and
increased insulin sensitivity. Stk25(-/-) mice were protected from diet-induced
liver steatosis accompanied by decreased protein levels of acetyl-CoA
carboxylase, a key regulator of both lipid oxidation and synthesis. Lipid
accumulation in Stk25(-/-) skeletal muscle was reduced, and expression of enzymes
controlling the muscle oxidative capacity (Cpt1, Acox1, Cs, Cycs, Ucp3) and
glucose metabolism (Glut1, Glut4, Hk2) was increased. These data are consistent
with our previous study of STK25 knockdown in myoblasts and reciprocal to the
metabolic phenotype of Stk25 transgenic mice, reinforcing the validity of the
results. The findings suggest that STK25 deficiency protects against the
metabolic consequences of chronic exposure to dietary lipids and highlight the
potential of STK25 antagonists for the treatment of type 2 diabetes.
PMID- 25845664
TI - Perceptions of private market landlords who rent to tenants of a Housing First
program.
AB - The rental of housing units by landlords to participants in Housing First (HF)
programs is critical to the success of these programs. Therefore, it is important
to understand the experiences of landlords with having these individuals as
tenants. The paper presents findings of qualitative interviews with 23 landlords
who rented to tenants from a HF program located in a small city and adjoining
rural area in eastern Canada and in which approximately 75 % of tenants had been
housed for at least six consecutive months at 2 years in the program. Findings
showed that landlords are motivated to rent to HF tenants for financial and pro
social reasons. They reported holding a range of positive, neutral, and negative
perceptions of these tenants. They identified problems encountered with some HF
tenants that included disruptive visitors, conflict with other tenants, constant
presence in their apartments, and poor upkeep of units. On the other hand,
landlords perceived HF tenants as being mostly good tenants who are similar to
their other tenants. Implications for practice in the context of HF programs are
discussed.
PMID- 25845662
TI - M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial
Nitric Oxide Signaling.
AB - Endothelial nitric oxide (NO) signaling plays a physiological role in limiting
obesity-associated insulin resistance and inflammation. This study was undertaken
to investigate whether this NO effect involves polarization of macrophages toward
an anti-inflammatory M2 phenotype. Mice with transgenic endothelial NO synthase
overexpression were protected against high-fat diet (HFD)-induced hepatic
inflammation and insulin resistance, and this effect was associated with reduced
proinflammatory M1 and increased anti-inflammatory M2 activation of Kupffer
cells. In cell culture studies, exposure of macrophages to endothelial NO
similarly reduced inflammatory (M1) and increased anti-inflammatory (M2) gene
expression. Similar effects were induced by macrophage overexpression of
vasodilator-stimulated phosphoprotein (VASP), a key downstream mediator of
intracellular NO signaling. Conversely, VASP deficiency induced proinflammatory
M1 macrophage activation, and the transplantation of bone marrow from VASP
deficient donor mice into normal recipients caused hepatic inflammation and
insulin resistance resembling that induced in normal mice by consumption of an
HFD. These data suggest that proinflammatory macrophage M1 activation and
macrophage-mediated inflammation are tonically inhibited by NO -> VASP signal
transduction, and that reduced NO -> VASP signaling is involved in the effect of
HFD feeding to induce M1 activation of Kupffer cells and associated hepatic
inflammation. Our data implicate endothelial NO -> VASP signaling as a
physiological determinant of macrophage polarization and show that signaling via
this pathway is required to prevent hepatic inflammation and insulin resistance.
PMID- 25845665
TI - Disclosure experiences of sexual minority college student victims of intimate
partner violence.
AB - Although research on disclosure following intimate partner violence (IPV)
victimization is burgeoning, sexual minority young adults' (lesbian, gay,
bisexual, queer, questioning, etc.; LGBQ+) experiences have not received equal
attention. The current study employed the minority stress framework to examine
disclosure experiences of LGBQ+ college students across the United States
reporting physical IPV victimization within their current relationship (n = 77).
Participants completed measures assessing minority stress and IPV disclosure, and
answered open-ended questions regarding the most and least helpful
persons/responses to disclosure or reasons for non-disclosure. Results indicated
that approximately one-third (35 %) of victims disclosed to at least one person,
with friends being the most common recipients. Thematic analyses indicated that
talking or listening to the victim was considered the most helpful response and
not understanding the situation least helpful. Reasons for non-disclosure
centered on themes of the victims' perception that the IPV was not a big deal.
Quantitative findings regarding physical IPV disclosure indicated that non
disclosers experienced greater minority stress than disclosers. The current study
suggests the presence of differences between sexual minority (i.e., LGBQ
+persons) and non-sexual minority persons, as well as between LGBQ+ young
adults/college students and older adults and presents a theoretical structure
(i.e., minority stress framework) through which these differences may be
understood.
PMID- 25845668
TI - Ultrasensitive room temperature NH3 sensor based on a graphene-polyaniline hybrid
loaded on PET thin film.
AB - This research was motivated by the need to develop a smart ammonia (NH3) sensor
based on a flexible polyethylene terephthalate (PET) thin film loaded with a
reduced graphene oxide-polyaniline (rGO-PANI hybrid) using in situ chemical
oxidative polymerization. The sensor not only exhibited high sensitivity, good
selectivity and a fast response at room temperature but was also flexible, cheap
and had wearable characteristics.
PMID- 25845666
TI - The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers
via the Akt pathway.
AB - Despite its importance, the death rate of ovarian cancer has remained unchanged
over the past five decades, demanding an improvement in prevention and treatment
of this malignancy. With no known carcinogens, targeted prevention is currently
unavailable, and efforts in early detection of this malignancy by screening
biomarkers have failed. The inhibition of angiogenesis, also known as
angioprevention, is a promising strategy to limit the growth of solid tumors,
including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated
from the tiansheng plant, has been shown to inhibit the growth of multiple types
of human cancers. However, there are no reports involving the effect on nobiletin
on human ovarian cancer. The present report shows that nobiletin potently
decreases the viability of ovarian cancer cells in vitro. However, nobiletin does
not affect the viability of normal ovarian epithelial cells at <40 uM. The
antitumor activity of nobiletin was also observed in athymic mouse models and in
chicken chorioallantoic membrane (CAM) models. The anti-neoplastic activity of
nobiletin was due to its ability to inhibit angiogenesis. We also studied the
molecular mechanisms by which nobiletin suppresses angiogenesis. We observed that
nobiletin inhibits secretion of the key angiogenesis mediators, Akt, HIF-1alpha,
NF-kappaB and vascular epithelial growth factor (VEGF) by ovarian cancer cells.
Transient transfection experiments showed that nobiletin inhibits production of
HIF-1alpha by downregulation of Akt. Such decreased levels of HIF-1alpha were
responsible for nobiletin-induced suppression of VEGF. Our data suggest that
nobiletin may be a promising anti-angiogenic agent relevant for therapy of
ovarian cancers.
PMID- 25845667
TI - Detection of endothelial progenitor cells in human skin wounds and its
application for wound age determination.
AB - Endothelial progenitor cells (EPCs), a newly identified cell type, are bone
marrow-derived progenitor cells that co-express stem cell markers and vascular
endothelial growth factor (VEGF) receptor (Flk-1). In this study, a double-color
immunofluorescence analysis was carried out using anti-CD34 and anti-Flk-1
antibodies to examine the time-dependent appearance of EPCs, using 52 human skin
wounds with different wound ages (Group I, 0-1 days; Group II, 2-6 days; Group
III, 7-14 days; and Group IV, 17-21 days). In wound specimens with an age of less
than one day, CD34(+)/Flk-1(+) EPCs were not detected. EPCs were initially
observed in wounds aged two days, and their number was increased in lesions with
advances in wound age. In morphometrical analysis, the average number of EPCs was
the highest in the wounds of Group III. Especially, 20 out of 21 wounds aged 7-12
days had >20 EPCs, and all wound samples with postinfliction intervals of 14-21
days had <15 EPCs. These observations at least showed that >20 EPCs would
indicate a wound age of 7-12 days. Taken together, our observations indicate the
detection of EPCs would be useful for wound age determination.
PMID- 25845669
TI - Guanine tetrads: an IRMPD spectroscopy, energy resolved SORI-CID, and
computational study of M(9-ethylguanine)(4)(+) (M = Li, Na, K, Rb, Cs) in the gas
phase.
AB - The intrinsic properties of the alkali metal cationized G-tetrads, M(9eG)4(+) (M
= Li, Na, K, Rb, Cs) composed of 9-ethylguanine (9eG), were studied by a
combination of mass spectrometric techniques. The gas phase structures were
probed by infrared multiple photon dissociation (IRMPD) spectroscopy in both the
fingerprint region (900-1850 cm(-1)) and the N-H/C-H stretching region (2700-3800
cm(-1)). The gas phase structures were found to be similar for all five complexes
and most consistent with the metal-centred G-tetrad structure. Energy-resolved
CID was also used to compare the gas phase stabilities of the G-tetrads and
showed that Na(9eG)4(+) was more stable than Li(9eG)4(+) followed by the K(+),
Rb(+), and Cs(+) G-tetrads in order. The experimental energy ordering was
reproduced by electronic structure calculations of the energies. Furthermore, the
computations also showed that the lower stability to loss of 9-ethylguanine for
the Li(+) complex could be due to a strong destabilization of the neutral G
tetrad due to the persistence toward maximizing the ion-dipole interactions while
also maintaining hydrogen bonding interactions.
PMID- 25845671
TI - The fifty most cited Italian articles in the orthopaedic literature.
AB - PURPOSES: It is widely known that in Orthopaedics, as in each specialty, the
academic influence of an article is also determined by the number of times the
article is cited. The aim of this study was to identify the 50 most frequently
cited Italian orthopaedics journal articles and to analyse the characteristics
that might have made them more citable. METHODS: Science Citation Index Expanded
was searched for the 50 most frequently cited Italian orthopaedics journal
articles between 1988 and 2013 in the subject category "Orthopaedics". RESULTS:
The 50 most frequently cited articles were all published in English and were
published in 12 of the 67 journals in the subject category "Orthopaedics" in the
Institute for Scientific Information Web Science (Thomson Reuters, New York, New
York, USA). One half of the articles were published before 2000 and the other
half later. The number of citations ranged from 423 of the first article (mean
citation/years 21.15) to 83 of the fiftieth (mean citation/years 16.60). The
articles were all categorized under orthopaedic field, but each of them spanned
from orthopaedics to a specific sub-specialty. The majority was clinical articles
(n = 39), and the most common fields were sport orthopaedic surgery (including
arthroscopy and cartilage) (n = 19) and biomechanics (n = 12). CONCLUSIONS: This
list of 50 most frequently cited Italian articles is, to our knowledge,
significantly important for the general orthopaedic scientific community,
particularly for the Italian orthopaedic community. Researchers and doctors may
use this work to make their future publications more influential and citable.
PMID- 25845670
TI - Autologous bone graft harvesting: a review of grafts and surgical techniques.
AB - Spinal fusion with or without instrumentation often requires the use of bone
graft. Bone graft may be autogenous or exogenous. There are various forms of bone
graft which may be acquired from numerous sites. Knowledge of fusion biology is
imperative for understanding the benefits and limitations of these grafts.
Equally as important is the knowledge of outcome measures, management of donor
site morbidity, and potential reconstruction. This review details the methods of
obtaining bone graft and details the properties of each, as well as discusses
observed outcomes, donor-site morbidities, and reconstruction techniques.
PMID- 25845672
TI - Compliance of blood donation apps with mobile OS usability guidelines.
AB - The aim of this paper is to employ the guidelines of Android, iOS, Blackberry and
Windows Phone to analyze the usability compliance of free blood donation (BD)
apps. An analysis process based on a systematic review protocol is used to select
free BD apps. An assessment is conducted using a questionnaire composed of 13
questions concerning the compliance of free BD apps with Android, Blackberry, iOS
and Windows Phone usability guidelines. A total of 133 free BD apps have been
selected from the 188 BD apps identified. Around 63% of the free BD apps selected
have a good compliance with mobile OS usability recommendations. Around 72% of
Android, 57% of Windows Phone, 33% of iOS and 33% of Blackberry BD apps have a
high usability score. The aspect of BD app behavior should be improved along with
some style components: the use of pictures to explain ideas and the adaptation of
the app to both horizontal and vertical orientations. Structure patterns should
also be used to improve the structure aspect of a BD app. Usability is a quality
aspect that should be improved in current BD apps. Our study provides smartphone
users with a list of usable free BD apps and BD app developers with
recommendations.
PMID- 25845673
TI - The Inflammatory Hypothesis of Atrial Fibrillation: Diagnostic Marker,
Therapeutic Target, or Innocent Bystander?
PMID- 25845674
TI - Determined to Die! Ability to Act Following Multiple Self-inflicted Gunshot
Wounds to the Head. The Cook County Office of Medical Examiner Experience (2005
2012) and Review of Literature.
AB - Cases of multiple (considered 2+) self-inflicted gunshot wounds are a rarity and
require careful examination of the scene of occurrence; thorough consideration of
the decedent's psychiatric, medical, and social histories; and accurate
postmortem documentation of the gunshot wounds. We present a series of four cases
of multiple self-inflicted gunshot wounds to the head from the Cook County
Medical Examiner's Office between 2005 and 2012 including the first case report
of suicide involving eight gunshot wounds to the head. In addition, a review of
the literature concerning multiple self-inflicted gunshot wounds to the head is
performed. The majority of reported cases document two gunshot entrance wound
defects. Temporal regions are the most common affected regions (especially the
right and left temples). Determining the capability to act following a gunshot
wound to the head is necessary in crime scene reconstruction and in
differentiation between homicide and suicide.
PMID- 25845675
TI - The different role of sex hormones on female cardiovascular physiology and
function: not only oestrogens.
AB - Human response to different physiologic stimuli and cardiovascular (CV)
adaptation to various pathologies seem to be gender specific. Sex-steroid
hormones have been postulated as the major contributors towards these sex-related
differences. This review will discuss current evidence on gender differences in
CV function and remodelling, and will present the different role of the principal
sex-steroid hormones on female heart. Starting from a review of sex hormones
synthesis, receptors and CV signalling, we will summarize the current knowledge
concerning the role of sex hormones on the regulation of our daily activities
throughout the life, via the modulation of autonomic nervous system, excitation
contraction coupling pathway and ion channels activity. Many unresolved questions
remain even if oestrogen effects on myocardial remodelling and function have been
extensively studied. So this work will focus attention also on the controversial
and complex relationship existing between androgens, progesterone and female
heart.
PMID- 25845676
TI - Targeted metabolic profiling of wounds in diabetic and nondiabetic mice.
AB - While cellular metabolism is known to regulate a number of key biological
processes such as cell growth and proliferation, its role in wound healing is
unknown. We hypothesized that cutaneous injury would induce significant metabolic
changes and that the impaired wound healing seen in diabetes would be associated
with a dysfunctional metabolic response to injury. We used a targeted
metabolomics approach to characterize the metabolic profile of uninjured skin and
full-thickness wounds at day 7 postinjury in nondiabetic (db/-) and diabetic
(db/db) mice. By liquid chromatography mass spectrometry, we identified 129
metabolites among all tissue samples. Principal component analysis demonstrated
that uninjured skin and wounds have distinct metabolic profiles and that diabetes
alters the metabolic profile of both uninjured skin and wounds. Examining
individual metabolites, we identified 62 with a significantly altered response to
injury in the diabetic mice, with many of these, including glycine, kynurenate,
and OH-phenylpyruvate, implicated in wound healing for the first time. Thus, we
report the first comprehensive analysis of wound metabolic profiles, and our
results highlight the potential for metabolomics to identify novel biomarkers and
therapeutic targets for improved wound healing outcomes.
PMID- 25845677
TI - Development of the affinity materials for phosphorylated proteins/peptides
enrichment in phosphoproteomics analysis.
AB - Reversible protein phosphorylation is a key event in numerous biological
processes. Mass spectrometry (MS) is the most powerful analysis tool in modern
phosphoproteomics. However, the direct MS analysis of phosphorylated
proteins/peptides is still a big challenge because of the low abundance and
insufficient ionization of phosphorylated proteins/peptides as well as the
suppression effects of nontargets. Enrichment of phosphorylated proteins/peptides
by affinity materials from complex biosamples is the most widely used strategy to
enhance the MS detection. The demand of efficiently enriching phosphorylated
proteins/peptides has spawned diverse affinity materials based on different
enrichment principles (e.g., electronic attraction, chelating). In this review,
we summarize the recent development of various affinity materials for
phosphorylated proteins/peptides enrichment. We will highlight the design and
fabrication of these affinity materials, discuss the enrichment mechanisms
involved in different affinity materials, and suggest the future challenges and
research directions in this field.
PMID- 25845679
TI - The effects of slope and branch structure on the locomotion of a specialized
arboreal colubrid snake (Boiga irregularis).
AB - The surfaces in arboreal habitats have variable diameters, slopes, and branching
structure that pose functional challenges for animal locomotion. Nevertheless,
many lineages of snakes have independently evolved arboreality. We tested the
effects of arboreal habitat structure on the locomotion of a highly arboreal
species, the brown tree snake (Boiga irregularis), moving on seven diameters (0.6
21 cm) of cylinders oriented at three slopes (0 degrees , 45 degrees , 90 degrees
) and with or without pegs. Intermediate diameters of horizontal cylinders
maximized speed, and some of the large-diameter cylinders without pegs were
impassable when they were inclined. With increased slope the snakes were slower,
and they changed from using lateral undulation with sliding contact and balancing
to concertina locomotion with periodic static gripping. The presence of pegs
increased the speeds of the brown tree snakes and resulted in them only using
lateral undulation. Surface diameter, slope, and the occurrence of pegs also had
widespread significant effects on the kinematics of the brown tree snakes.
Overall, compared to anatomically less specialized corn snakes, brown tree snakes
use more lateral undulation, are usually much faster, and are able to move on a
wider variety of surfaces. Unlike some of the trade-offs found previously between
two less specialized species of snakes with different stoutness when they used
modes of arboreal locomotion that involved either balancing or gripping, the
slender-bodied brown tree snakes excel at both. Hence, this species may not only
be a "jack of all trades" but also a master of many.
PMID- 25845678
TI - Falls in ambulatory non-demented patients with Parkinson's disease.
AB - This study aimed at determining the prevalence of falling in PD patients, to
assess generic and disease-specific clinical and pharmacological factors,
relationship with health-related quality of life (HR-QoL) and changes in falls
from OFF to ON in patients with motor fluctuations. Six-hundred and eighty-three
PD patients of the COPARK survey were evaluated (11 had missing data and were
excluded from the analysis). Patients with falls were identified as those with a
UPDRS Item 13 >= 1 in the ON condition. All patients were assessed in a
standardized manner [demographics, treatments, Unified PD Rating Scale (UPDRS),
Hospital Anxiety and Depression Scale, Pittsburg questionnaire and HR-QoL scales
(SF36, PDQ39)]. Falling was reported by 108/672 (16%) PD patients during the ON
state and prevalence increased according to PD severity, from 5% in Hoehn and
Yahr stage 1-60% in stage 4. Falling was significantly related to lower HR-QoL.
Falling correlated with (1) generic factors such as female gender, age at the end
of academic studies and diuretics consumption, (2) motor PD-specific factors
including disease severity, frozen gait, difficulties when arising from a chair,
dyskinesia and higher levodopa daily equivalent dose and (3) non-motor PD
specific factors such as orthostatic hypotension and hallucinations. Falling was
more frequent in OFF than in ON in 48/74 (64%) patients with motor fluctuations
and remained unchanged in 27 patients (36%). In summary, falling affected a
significant proportion of PD patients, especially in advanced stages. It was
associated with a variety of generic and PD-specific factors and was related to
reduced HR-QoL.
PMID- 25845680
TI - Synbiotics-supplemented amino acid-based formula supports adequate growth in
cow's milk allergic infants.
AB - BACKGROUND: Children with cow's milk allergy (CMA) are at risk for inadequate
nutritional intake and growth. Dietary management of CMA, therefore, requires
diets that are not only hypoallergenic but also support adequate growth in this
population. This study assessed growth of CMA infants when using a new amino acid
based formula (AAF) with prebiotics and probiotics (synbiotics) and evaluated its
safety in the intended population. METHODS: In a prospective, randomized, double
blind controlled study, full-term infants with diagnosed CMA received either an
AAF (control; n = 56) or AAF with synbiotics (oligofructose, long-chain inulin,
acidic oligosaccharides, Bifidobacterium breve M-16V) (test; n = 54) for 16 wk.
Primary outcome was growth, measured as weight, length and head circumference.
Secondary outcomes included allergic symptoms and stool characteristics. RESULTS:
Average age (+/-SD) of infants at inclusion was 4.5 +/- 2.4 months. Both formulas
equally supported growth according to WHO 2006 growth charts and resulted in
similar increases of weight, length and head circumference. At week 16,
differences (90% CI) in Z-scores (test-control) were as follows: weight 0.147 (
0.10; 0.39, p = 0.32), length -0.299 (-0.69; 0.09, p = 0.21) and head
circumference 0.152 (-0.15; 0.45, p = 0.40). Weight-for-age and length-for-age Z
scores were not significantly different between the test and control groups. Both
formulas were well tolerated and reduced allergic symptoms; the number of adverse
events was not different between the groups. CONCLUSIONS: This is the first study
that shows that an AAF with a specific synbiotic blend, suitable for CMA infants,
supports normal growth and growth similar to the AAF without synbiotics. This
clinical trial is registered as NCT00664768.
PMID- 25845681
TI - Icariin regulates the proliferation and apoptosis of human ovarian cancer cells
through microRNA-21 by targeting PTEN, RECK and Bcl-2.
AB - Icariin is the main active ingredient found in the traditional Chinese medicinal
plant Epimedium, and exhibits various pharmacological effects such as enhanced
immune function, anticancer activity, improved cardiovascular function and
endocrine adjustment. However, the effect of icariin on ovarian cancer and the
related mechanism have never been investigated. In the present study, we aimed to
verify whether icariin inhibits the proliferation and increases the apoptosis of
human ovarian cancer cells, and its molecular mechanism in order to establish an
association and identify potential therapeutic targets. In the present study,
ovarian cancer A2780 cells were treated with various concentrations of icariin,
and the cell viability was evaluated by 3,3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) assay. Flow cytometry and caspase-3
colorimetric assay were performed to observe apoptotic changes in the A2780
cells. qPCR analysis was used to analyze miR-21 expression in the A2780 cells.
Western blot analysis was used to assess PTEN, RECK and Bcl-2 protein expression.
Transfection of microRNA-21 (miR-21) and anti-miR-21 was used to investigate
expression of its target genes associated with cell proliferation and apoptosis.
Icariin concomitantly suppressed cell proliferation, accelerated apoptosis and
increased caspase-3 activity in the A2780 cells. In the ovarian cancer A2780
cells, icariin substantially decreased the miR-21 expression level, increased
PTEN and RECK protein expression levels and decreased the Bcl-2 protein
expression level. Notably, miR-21 regulated the potential anticancer effects of
icariin on cell proliferation and apoptosis by targeting PTEN, RECK and Bcl-2 in
the ovarian cancer A2780 cells. Our results demonstrated that icariin is an
excellent candidate antitumor agent which exhibits an anticancer curative effect
on ovarian cancer cells. miR-21 and its target genes may play a vital role in the
molecular mechanism of the anticancer effects of icariin.
PMID- 25845682
TI - Half a century of the Burgenstock Conference: a pilgrim's tale.
AB - "...? The Burgenstock program always allows for important scientific discussion.
It is clear that this meeting is valuable for the scientific community as it is
on one hand important for its deep historical significance, and on the other hand
crucial for what it preserves of great scientific tradition for future
generations. Every meeting contained a lesson learned and further brought
together the family of stereochemists ...?" Read more in the Editorial by Jay S.
Siegel.
PMID- 25845683
TI - Obstructive sleep apnea: how much is too much?
PMID- 25845684
TI - On the role of sleep intensity in a model of sleep regulation.
PMID- 25845685
TI - Shooting STAR: Caution in Interpreting Long-Term Cost Effectiveness from a Short
Term Case-Series.
PMID- 25845686
TI - The Multidimensional Aspects of Sleep Spindles and Their Relationship to Word
Pair Memory Consolidation.
AB - STUDY OBJECTIVES: Several studies proposed a link between sleep spindles and
sleep dependent memory consolidation in declarative learning tasks. In addition
to these state-like aspects of sleep spindles, they have also trait-like
characteristics, i.e., were related to general cognitive performance, an
important distinction that has often been neglected in correlative studies.
Furthermore, from the multitude of different sleep spindle measures, often just
one specific aspect was analyzed. Thus, we aimed at taking multidimensional
aspects of sleep spindles into account when exploring their relationship to word
pair memory consolidation. DESIGN: Each subject underwent 2 study nights with all
night high-density electroencephalographic (EEG) recordings. Sleep spindles were
automatically detected in all EEG channels. Subjects were trained and tested on a
word-pair learning task in the evening, and retested in the morning to assess
sleep related memory consolidation (overnight retention). Trait-like aspects
refer to the mean of both nights and state-like aspects were calculated as the
difference between night 1 and night 2. SETTING: Sleep laboratory. PARTICIPANTS:
Twenty healthy male subjects (age: 23.3 +/- 2.1 y). MEASUREMENTS AND RESULTS:
Overnight retention was negatively correlated with trait-like aspects of fast
sleep spindle density and positively with slow spindle density on a global level.
In contrast, state-like aspects were observed for integrated slow spindle
activity, which was positively related to the differences in overnight retention
in specific regions. CONCLUSION: Our results demonstrate the importance of a
multidimensional approach when investigating the relationship between sleep
spindles and memory consolidation and thereby provide a more complete picture
explaining divergent findings in the literature.
PMID- 25845687
TI - Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and
Related Hypoxemia.
AB - STUDY OBJECTIVES: The catalytic function of the enzyme carbonic anhydrase (CA)
plays a fundamental role in carbon dioxide (CO2), proton (H(+)), and bicarbonate
(HCO3(-)) homeostasis. Hypoxia and tissue acidosis have been proposed to increase
physiological CA activity in various compartments of the body. We hypothesized
that CA activity in blood is upregulated in patients with obstructive sleep apnea
(OSA). DESIGN: Cross-sectional analysis of a sleep clinic cohort. SETTINGS: Sleep
laboratory at a university hospital. PARTICIPANTS: Seventy referred patients with
suspected OSA (48 males, age 54 +/- 13 y, apnea-hypopnea index (AHI) median
[interquartile range] 21 [8-41] n/h). INTERVENTIONS: N/A. MEASUREMENTS AND
RESULTS: In-laboratory cardiorespiratory polygraphy was used to assess OSA. CA
activity was determined by an in vitro assay that quantifies the pH change
reflecting the conversion of CO2 and H2O to HCO3(-) and H(+). CA activity was
positively associated with AHI and 4% oxygen desaturation index (ODI4) (Spearman
correlation r = 0.44 and 0.47, both P < 0.001). The associations (CA activity
versus logAHI and CA versus logODI4) were independent of sex, age, body mass
index, presleep oxygen saturation, nocturnal oxygen saturation, hypertension
status, and use of diuretic medication in two generalized linear models (P =
0.007 and 0.011, respectively). Sitting diastolic blood pressure was associated
with CA activity after adjustment of sex, age, body mass index, mean oxygen
saturation, and AHI (P = 0.046). CONCLUSIONS: Carbonic anhydrase (CA) activity
increased with apnea-hypopnea index and related nocturnal hypoxemia measures in
patients with obstructive sleep apnea (OSA). Altered CA activity may constitute a
component that modulates respiratory control and hemodynamic regulation in
patients with OSA.
PMID- 25845688
TI - African Genetic Ancestry is Associated with Sleep Depth in Older African
Americans.
AB - STUDY OBJECTIVES: The mechanisms that underlie differences in sleep
characteristics between European Americans (EA) and African Americans (AA) are
not fully known. Although social and psychological processes that differ by race
are possible mediators, the substantial heritability of sleep characteristics
also suggests genetic underpinnings of race differences. We hypothesized that
racial differences in sleep phenotypes would show an association with objectively
measured individual genetic ancestry in AAs. DESIGN: Cross sectional. SETTING:
Community-based study. PARTICIPANTS: Seventy AA adults (mean age 59.5 +/- 6.7 y;
62% female) and 101 EAs (mean age 60.5 +/- 7 y, 39% female). MEASUREMENTS AND
RESULTS: Multivariate tests were used to compare the Pittsburgh Sleep Quality
Index (PSQI) and in-home polysomnographic measures of sleep duration, sleep
efficiency, apnea-hypopnea index (AHI), and indices of sleep depth including
percent visually scored slow wave sleep (SWS) and delta EEG power of EAs and AAs.
Sleep duration, efficiency, and sleep depth differed significantly by race.
Individual % African ancestry (%AF) was measured in AA subjects using a panel of
1698 ancestry informative genetic markers and ranged from 10% to 88% (mean 67%).
Hierarchical linear regression showed that higher %AF was associated with lower
percent SWS in AAs (beta (standard error) = -4.6 (1.5); P = 0.002), and explained
11% of the variation in SWS after covariate adjustment. A similar association was
observed for delta power. No association was observed for sleep duration and
efficiency. CONCLUSION: African genetic ancestry is associated with indices of
sleep depth in African Americans. Such an association suggests that part of the
racial differences in slow-wave sleep may have genetic underpinnings.
PMID- 25845689
TI - Increased Automaticity and Altered Temporal Preparation Following Sleep
Deprivation.
AB - STUDY OBJECTIVES: Temporal expectation enables us to focus limited processing
resources, thereby optimizing perceptual and motor processing for critical
upcoming events. We investigated the effects of total sleep deprivation (TSD) on
temporal expectation by evaluating the foreperiod and sequential effects during a
psychomotor vigilance task (PVT). We also examined how these two measures were
modulated by vulnerability to TSD. DESIGN: Three 10-min visual PVT sessions using
uniformly distributed foreperiods were conducted in the wake-maintenance zone the
evening before sleep deprivation (ESD) and three more in the morning following
approximately 22 h of TSD. TSD vulnerable and nonvulnerable groups were
determined by a tertile split of participants based on the change in the number
of behavioral lapses recorded during ESD and TSD. A subset of participants
performed six additional 10-min modified auditory PVTs with exponentially
distributed foreperiods during rested wakefulness (RW) and TSD to test the effect
of temporal distribution on foreperiod and sequential effects. SETTING: Sleep
laboratory. PARTICIPANTS: There were 172 young healthy participants (90 males)
with regular sleep patterns. Nineteen of these participants performed the
modified auditory PVT. MEASUREMENTS AND RESULTS: Despite behavioral lapses and
slower response times, sleep deprived participants could still perceive the
conditional probability of temporal events and modify their level of preparation
accordingly. Both foreperiod and sequential effects were magnified following
sleep deprivation in vulnerable individuals. Only the foreperiod effect increased
in nonvulnerable individuals. CONCLUSIONS: The preservation of foreperiod and
sequential effects suggests that implicit time perception and temporal
preparedness are intact during total sleep deprivation. Individuals appear to
reallocate their depleted preparatory resources to more probable event timings in
ongoing trials, whereas vulnerable participants also rely more on automatic
processes.
PMID- 25845690
TI - Nocturnal Sleep Dynamics Identify Narcolepsy Type 1.
AB - STUDY OBJECTIVES: To evaluate the reliability of nocturnal sleep dynamics in the
differential diagnosis of central disorders of hypersomnolence. DESIGN: Cross
sectional. SETTING: Sleep laboratory. PATIENTS: One hundred seventy-five patients
with hypocretin-deficient narcolepsy type 1 (NT1, n = 79), narcolepsy type 2
(NT2, n = 22), idiopathic hypersomnia (IH, n = 22), and "subjective"
hypersomnolence (sHS, n = 52). INTERVENTIONS: None. METHODS: Polysomnographic
(PSG) work-up included 48 h of continuous PSG recording. From nocturnal PSG
conventional sleep macrostructure, occurrence of sleep onset rapid eye movement
period (SOREMP), sleep stages distribution, and sleep stage transitions were
calculated. Patient groups were compared, and receiver operating characteristic
(ROC) curve analysis was used to test the diagnostic utility of nocturnal PSG
data to identify NT1. RESULTS: Sleep macrostructure was substantially stable in
the 2 nights of each diagnostic group. NT1 and NT2 patients had lower latency to
rapid eye movement (REM) sleep, and NT1 patients showed the highest number of
awakenings, sleep stage transitions, and more time spent in N1 sleep, as well as
most SOREMPs at daytime PSG and at multiple sleep latency test (MSLT) than all
other groups. ROC curve analysis showed that nocturnal SOREMP (area under the
curve of 0.724 +/- 0.041, P < 0.0001), percent of total sleep time spent in N1
(0.896 +/- 0.023, P < 0.0001), and the wakefulness-sleep transition index (0.796
+/- 0.034, P < 0.0001) had a good sensitivity and specificity profile to identify
NT1 sleep, especially when used in combination (0.903 +/- 0.023, P < 0.0001),
similarly to SOREMP number at continuous daytime PSG (0.899 +/- 0.026, P <
0.0001) and at MSLT (0.956 +/- 0.015, P < 0.0001). CONCLUSIONS: Sleep
macrostructure (i.e. SOREMP, N1 timing) including stage transitions reliably
identifies hypocretin-deficient narcolepsy type 1 among central disorders of
hypersomnolence.
PMID- 25845691
TI - Trajectories of Sleep Quality and Associations with Mood during the Perinatal
Period.
AB - OBJECTIVE: The aim of this study was to investigate trajectories of sleep quality
and associations with mood in the perinatal period. Although it is commonly
accepted that subjective sleep quality declines during pregnancy and the
transition to parenthood, some women may follow qualitatively distinct
trajectories. DESIGN, SETTING, AND PARTICIPANTS: Sleep quality was assessed by
the Pittsburgh Sleep Quality Index (PSQI). Data were collected from 293 women at
four time points: during early pregnancy, at Time 1 (T1; < 22 w gestational age
[GA]; late pregnancy, at Time 2 (T2; 32 w GA); during the postnatal period at
Time 3 (T3; 3 mo postpartum); and Time 4 (T4; 6 mo postpartum). A group-based
semiparametric mixture model was used to estimate patterns of sleep quality
throughout the perinatal period. RESULTS: Four trajectory groups were identified,
including patterns defined by high sleep quality throughout (21.5%), mild
decrease in sleep quality (59.5%), significant decrease in sleep quality (12.3%)
and a group with poor sleep quality throughout (6.7%). Women who had the worst
sleep quality at Time 1 and those who experienced significant increases in sleep
problems throughout pregnancy were also the groups who reported the highest
levels of anxiety and depressive symptoms in early pregnancy and the lowest
levels of social support. After controlling for covariates, the groups with worst
subjective sleep quality during pregnancy were also the most likely to experience
high symptoms of depression in the postpartum period. CONCLUSIONS: Most of the
women in our sample reported mild sleep disturbances through the perinatal
period. A subgroup of women reported a significant decline in sleep quality from
early to late pregnancy and another reported poor subjective sleep quality
throughout pregnancy; these groups had the greatest risk of experiencing high
symptoms of depression in the postpartum period.
PMID- 25845692
TI - The Role of the Serotonergic System in REM Sleep Behavior Disorder.
AB - STUDY OBJECTIVES: REM sleep behavior disorder (RBD) can be induced by
antidepressants, especially serotonin reuptake inhibitors (SSRI), thus a role of
the serotonergic system in the pathogenesis of RBD has been proposed. However,
the serotonergic system integrity in idiopathic RBD (iRBD) is still unknown. We
aimed to study brain stem serotonergic system integrity, by means of (123)I-FP
CIT-SPECT, in a group of iRBD patients as compared to normal subjects. DESIGN:
Single-center, prospective observational study. SETTING: University hospital.
PATIENTS OR PARTICIPANTS: Twenty iRBD outpatients and 23 age-matched normal
controls. MEASUREMENTS AND RESULTS: The diagnosis of RBD was determined
clinically and confirmed by means of overnight, laboratory-based video
polysomnography. Both iRBD patients and normal subjects underwent (123)I-FP-CIT
SPECT as a marker of dopamine transporter (DAT) at basal ganglia level and of
serotonin transporter (SERT) at brainstem and thalamus levels. (123)I-FP-CIT
SPECT images were analyzed and compared between iRBD patients and controls by
means of both region of interest analysis at basal ganglia, midbrain, pons and
thalamus levels, and voxel-based analysis, taking into account age and the use of
SSRI as confounding factors. No difference in (123)I-FP-CIT-SPECT specific to
nondisplaceable binding ratios (SBR) values was found between iRBD and normal
subjects at brainstem and thalamus levels while iRBD patients showed lower SBR
values in all basal ganglia nuclei (P < 0.0001) compared to controls.
CONCLUSIONS: These results suggest that the serotonergic system is not directly
involved in RBD pathogenesis while confirming nigro-striatal dopaminergic
deafferentation in iRBD.
PMID- 25845693
TI - Poor Sleep Quality and Associated Inflammation Predict Preterm Birth: Heightened
Risk among African Americans.
AB - STUDY OBJECTIVES: Poor sleep promotes inflammation. In turn, inflammation is a
causal mechanism in term as well as preterm parturition. In the United States, a
persistent racial disparity in preterm birth exists, with African Americans
showing ~1.5 times greater risk. This study examined associations among sleep
quality, serum proinflammatory cytokines, and length of gestation in a racially
diverse sample of 138 pregnant women. DESIGN: Observational. MEASUREMENTS: Women
completed the Pittsburgh Sleep Quality Index (PSQI) and other psychosocial and
behavioral measures during midpregnancy. Serum levels of interleukin (IL)-6, IL
8, IL-1beta, and tumor necrosis factor (TNF)-alpha were determined by high
sensitivity assays. Birth outcomes were determined via medical record review.
RESULTS: Among African American women (n = 79), shorter gestation was predicted
by poorer overall sleep (rs = -0.35, P = 0.002) as well the following PSQI
subscales: subjective sleep quality (rs = -0.34, P = 0.002), sleep latency (rs =
0.27, P = 0.02), and sleep efficiency (rs = -0.27, P = 0.02). African American
women with poor sleep quality (PSQI > 5) had 10.2 times the odds of preterm birth
compared to those with good sleep quality. In contrast, among European American
women (n = 53), gestational length was not significantly predicted by sleep
quality (Ps > 0.12). Bootstrapping analyses showed that, among African Americans,
IL-8 significantly mediated the association between sleep quality and length of
gestation (indirect effect estimate -0.029; 95% confidence interval -0.06,
0.002). CONCLUSIONS: The data provide novel evidence that African American women
exhibit greater inflammation in response to sleep disturbance than European
American women and these effects correspond with length of gestation. Racial
differences in susceptibility to sleep induced immune dysregulation may
contribute to marked racial disparities in preterm birth.
PMID- 25845694
TI - Sleep Disordered Breathing in Four Resource-Limited Settings in Peru: Prevalence,
Risk Factors, and Association with Chronic Diseases.
AB - STUDY OBJECTIVES: Sleep disordered breathing (SDB) is a highly prevalent
condition in high-income countries, with major consequences for cardiopulmonary
health, public safety, healthcare utilization, and mortality. However, its
prevalence and effect in low- and middle-income countries are less well known. We
sought to determine the prevalence, risk factors, and comorbidities of SDB
symptoms in four resource-limited settings. DESIGN: Cross-sectional analysis of
the CRONICAS Cohort, a population-based age- and sex-stratified sample. SETTING:
Four resource-limited settings in Peru varying in altitude, urbanization, and air
pollution. PARTICIPANTS: There were 2,682 adults aged 35 to 92 y. MEASUREMENTS
AND RESULTS: Self-reported SDB symptoms (habitual snoring, observed apneas,
Epworth Sleepiness Scale), sociodemographics, medical history, anthropometrics,
spirometry, blood biomarkers were reported. We found a high prevalence of
habitual snoring (30.2%, 95% confidence interval [CI] 28.5-32.0%), observed
apneas (20.9%, 95% CI 19.4-22.5%) and excessive daytime sleepiness (18.6%, 95% CI
17.1-20.1%). SDB symptoms varied across sites; prevalence and adjusted odds for
habitual snoring were greatest at sea level, whereas those for observed apneas
were greatest at high altitude. In multivariable analysis, habitual snoring was
associated with older age, male sex, body mass index (BMI), and higher
socioeconomic status; observed apneas were associated with BMI; and excessive
daytime sleepiness was associated with older age, female sex, and medium
socioeconomic status. Adjusted odds of cardiovascular disease, depression, and
hypertension and total chronic disease burden increased progressively with the
number of SDB symptoms. A threefold increase in the odds of having an additional
chronic comorbid disease (adjusted odds ratio 3.57, 95% CI 2.18-5.84) was
observed in those with all three versus no SDB symptoms. CONCLUSIONS: Sleep
disordered breathing symptoms were highly prevalent, varied widely across four
resource-limited settings in Peru, and exhibited strong independent associations
with chronic diseases.
PMID- 25845695
TI - Cacna1c (Cav1.2) Modulates Electroencephalographic Rhythm and Rapid Eye Movement
Sleep Recovery.
AB - STUDY OBJECTIVES: The CACNA1C gene encodes the alpha 1C (alpha1C) subunit of the
Cav1.2 voltage-dependent L-type calcium channel (LTCC). Some of the other voltage
dependent calcium channels, e.g., P-/Q-type, Cav2.1; N-type, Cav2.2; E-/R-type,
Cav2.3; and T-type, Cav3.3 have been implicated in sleep modulation. However, the
contribution of LTCCs to sleep remains largely unknown. Based on recent genome
wide association studies, CACNA1C emerged as one of potential candidate genes
associated with both sleep and psychiatric disorders. Indeed, most patients with
mental illnesses have sleep problems and vice versa. DESIGN: To investigate an
impact of Cav1.2 on sleep-wake behavior and electroencephalogram (EEG) activity,
polysomnography was performed in heterozygous Cacna1c (HET) knockout mice and
their wild-type (WT) littermates under baseline and challenging conditions (acute
sleep deprivation and restraint stress). MEASUREMENTS AND RESULTS: HET mice
displayed significantly lower EEG spectral power than WT mice across high
frequency ranges (beta to gamma) during wake and rapid eye movement (REM) sleep.
Although HET mice spent slightly more time asleep in the dark period, daily
amounts of sleep did not differ between the two genotypes. However, recovery
sleep after exposure to both types of challenging stress conditions differed
markedly; HET mice exhibited reduced REM sleep recovery responses compared to WT
mice. CONCLUSIONS: These results suggest the involvement of Cacna1c (Cav1.2) in
fast electroencephalogram oscillations and REM sleep regulatory processes. Lower
spectral gamma activity, slightly increased sleep demands, and altered REM sleep
responses found in heterozygous Cacna1c knockout mice may rather resemble a sleep
phenotype observed in schizophrenia patients.
PMID- 25845697
TI - Reproducibility of a Standardized Actigraphy Scoring Algorithm for Sleep in a US
Hispanic/Latino Population.
AB - STUDY OBJECTIVES: While actigraphy is considered objective, the process of
setting rest intervals to calculate sleep variables is subjective. We sought to
evaluate the reproducibility of actigraphy-derived measures of sleep using a
standardized algorithm for setting rest intervals. DESIGN: Observational study.
SETTING: Community-based. PARTICIPANTS: A random sample of 50 adults aged 18-64
years free of severe sleep apnea participating in the Sueno sleep ancillary study
to the Hispanic Community Health Study/Study of Latinos. INTERVENTIONS: N/A.
MEASUREMENTS AND RESULTS: Participants underwent 7 days of continuous wrist
actigraphy and completed daily sleep diaries. Studies were scored twice by each
of two scorers. Rest intervals were set using a standardized hierarchical
approach based on event marker, diary, light, and activity data. Sleep/wake
status was then determined for each 30-sec epoch using a validated algorithm, and
this was used to generate 11 variables: mean nightly sleep duration, nap
duration, 24-h sleep duration, sleep latency, sleep maintenance efficiency, sleep
fragmentation index, sleep onset time, sleep offset time, sleep midpoint time,
standard deviation of sleep duration, and standard deviation of sleep midpoint.
Intra-scorer intraclass correlation coefficients (ICCs) were high, ranging from
0.911 to 0.995 across all 11 variables. Similarly, inter-scorer ICCs were high,
also ranging from 0.911 to 0.995, and mean inter-scorer differences were small.
Bland-Altman plots did not reveal any systematic disagreement in scoring.
CONCLUSIONS: With use of a standardized algorithm to set rest intervals, scoring
of actigraphy for the purpose of generating a wide array of sleep variables is
highly reproducible.
PMID- 25845696
TI - Promotion of Wakefulness and Energy Expenditure by Orexin-A in the Ventrolateral
Preoptic Area.
AB - STUDY OBJECTIVES: The ventrolateral preoptic area (VLPO) and the
orexin/hypocretin neuronal system are key regulators of sleep onset, transitions
between vigilance states, and energy homeostasis. Reciprocal projections exist
between the VLPO and orexin/hypocretin neurons. Although the importance of the
VLPO to sleep regulation is clear, it is unknown whether VLPO neurons are
involved in energy balance. The purpose of these studies was to determine if the
VLPO is a site of action for orexin-A, and which orexin receptor subtype(s) would
mediate these effects of orexin-A. We hypothesized that orexin-A in the VLPO
modulates behaviors (sleep and wakefulness, feeding, spontaneous physical
activity [SPA]) to increase energy expenditure. DESIGN AND MEASUREMENTS: Sleep,
wakefulness, SPA, feeding, and energy expenditure were determined after orexin-A
microinjection in the VLPO of male Sprague-Dawley rats with unilateral cannulae
targeting the VLPO. We also tested whether pretreatment with a dual orexin
receptor antagonist (DORA, TCS-1102) or an OX2R antagonist (JNJ-10397049) blocked
the effects of orexin-A on the sleep/wake cycle or SPA, respectively. RESULTS:
Orexin-A injected into the VLPO significantly increased wakefulness, SPA, and
energy expenditure (SPA-induced and total) and reduced NREM sleep and REM sleep
with no effect on food intake. Pretreatment with DORA blocked the increase in
wakefulness and the reduction in NREM sleep elicited by orexin-A, and the OX2R
antagonist reduced SPA stimulated by orexin-A. CONCLUSIONS: These data show the
ventrolateral preoptic area is a site of action for orexin-A, which may promote
negative energy balance by modulating sleep/wakefulness and stimulating
spontaneous physical activity and energy expenditure.
PMID- 25845698
TI - Polysomnographic Findings and Clinical Correlates in Huntington Disease: A Cross
Sectional Cohort Study.
AB - STUDY OBJECTIVES: To evaluate the sleep pattern and the motor activity during
sleep in a cohort of patients affected by Huntington disease (HD). DESIGN: Cross
sectional cohort study. SETTING: Sleep laboratory. PATIENTS: Thirty HD patients,
16 women and 14 men (mean age 57.3 +/- 12.2 y); 30 matched healthy controls (mean
age 56.5 +/- 11.8 y). INTERVENTIONS: Subjective sleep evaluation: Epworth
Sleepiness Scale (ESS); Berlin's Questionnaire, interview for restless legs
syndrome (RLS), questionnaire for REM sleep behavior disorder (RBD). Clinical
evaluation: disease duration, clinical severity (unified Huntington disease motor
rating scale [UHDMRS]), genetic tests. Laboratory-based full-night attended video
polysomnography (V-PSG). MEASUREMENTS AND RESULTS: The duration of the disease
was 9.4 +/- 4.4 y, UHMDRS score was 55.5 +/- 23.4, CAG repeats were 44.3 +/- 4.1.
Body mass index was 21.9 +/- 4.0 kg/m(2). No patients or caregivers reported poor
sleep quality. Two patients reported symptoms of RLS. Eight patients had an ESS
score >= 9. Eight patients had high risk of obstructive sleep apnea. At the RBD
questionnaire, two patients had a pathological score. HD patients, compared to
controls, showed shorter sleep, reduced sleep efficiency index, and increased
arousals and awakenings. Four patients presented with sleep disordered breathing
(SDB). Periodic limb movements (PLMs) during wake and sleep were observed in all
patients. No episode of RBD was observed in the V-PSG recordings, and no patients
showed rapid eye movement (REM) sleep without atonia. The disease duration
correlated with ESS score (P < 0.02). UHMDRS correlated positively with the ESS
score (P < 0.005), and negatively with the percentage of REM sleep. CONCLUSIONS:
Patients with Huntington disease showed a severe sleep disruption and a high
prevalence of periodic limb movements, but no evidence of sleep disordered
breathing or REM sleep behavior disorder.
PMID- 25845699
TI - Identification of NF-kappaB inhibitors in Qishenyiqi dropping pills for
myocardial infarction treatment based on bioactivity-integrated UPLC-Q/TOF MS.
AB - Qishenyiqi dropping pills (QSYQ) are a type of standardized cardiovascular
multiherb medicine for the treatment of myocardial infarction (MI). Knowledge
concerning the systemic identification of nuclear factor-kappa B (NF-kappaB)
inhibitors of QSYQ is generally lacking. Therefore, it is necessary to establish
an effective method to screen the bioactive components of NF-kappaB inhibition.
In the present study, a rat model of coronary artery ligation was used to assess
the cardioprotective effects of QSYQ. The electrocardiograms, histopathology of
heart tissues and serum biochemical indicators, such as brain natriuretic
peptide, cardiac troponin I and inflammatory cytokines, were measured.
Subsequently, ultra-performance liquid chromatography quadrupole/time-of-flight
mass spectrometry (UPLC-Q/TOF MS) combined with the NF-kappaB luciferase reporter
assay system was applied to screen the potential anti-inflammatory compounds in
QSYQ. The results revealed that the administration of QSYQ could improve heart
function, ameliorate neutrophil infiltration and diminish the levels of
inflammatory cytokines in MI rats. Furthermore, 22 compounds were determined to
be potential NF-kappaB inhibitors. In conclusion, NF-kappaB inactivation and
cytokine suppression might be the main mechanisms of QSYQ for MI treatment. The
method of UPLC-Q/TOF MS combined with a bioactive human cell functional
evaluation system was proved to be a simple and effective strategy for screening
bioactive compounds in traditional Chinese medicine prescriptions.
PMID- 25845700
TI - Twins' risk of childhood asthma mediated by gestational age and birthweight.
AB - BACKGROUND: Children born with low gestational age (GA) or low birthweight (BW)
are at increased risk of asthma. Twins as compared to singletons are on average
more likely to be born with lower GA and BW and have been hypothesized to
comprise a high-risk population for asthma. Many previous studies have not
accounted for potential confounders or mediators. OBJECTIVE: To investigate the
association between twinship and childhood asthma or early life wheeze and
identify potential mediators, such as GA/BW. METHODS: The study population
consisted of two cohorts including all children born in Sweden from 1 January
1993 to 1 June 2001 (n = 756,363 singletons, n = 22,478 twins) and 1 July 2005 to
31 December 2009 (n = 456,239 singletons, n = 12,872 twins). Asthma was defined
using validated register-based outcomes of diagnosis or medication. The data were
analysed using logistic (older cohort) and Cox regression (younger cohort).
Adjusted models incorporated potential confounding or mediating factors including
gestational age and birthweight. RESULTS: In the younger cohort, the crude hazard
ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01
1.23), and fully adjusted HR was 0.80, 95% CI 0.72-0.89. Crude HR of asthma
diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78
(0.68-0.98). Adjusted analyses in the older group yielded similar results.
CONCLUSIONS: Twins were at significantly higher unadjusted risk of asthma or
early life wheeze compared to singletons in the younger, but not in the older
cohort. Associations attenuated following adjustment for GA/BW, suggesting that
GA/BW mediates the effect of twinship on asthma risk. After adjustments, twins
were at lower risk of asthma outcomes, possibly due to unmeasured confounding.
PMID- 25845701
TI - Peritumoral dermis of squamous cell carcinomas in renal transplant recipients
contains less CD11c+ myeloid dendritic cells and FoxP3+ T cells compared to
immunocompetent controls.
AB - BACKGROUND: Renal transplant recipients (RTR) have an increased risk of
developing cutaneous squamous cell carcinomas (SCC). These SCC are often more
aggressive than SCC in immunocompetent individuals. OBJECTIVES: In this
comparative study, we analysed the cell composition in the tissue immediately
surrounding invasive SCC in immunosuppressed RTR and immunocompetent controls in
an effort to further elucidate the role of the local immune system. METHODS:
Morphology and quantity of various dendritic cell (DC) subsets, macrophages and
FoxP3+ T cells were analysed by immunohistochemical staining. RESULTS: The number
of CD11c+ myeloid DC and FoxP3+ T cells was significantly reduced in RTR, whereas
the number of plasmacytoid DC, Langerhans cells and macrophages was similar in
RTR and controls. CONCLUSIONS: A reduction in CD11c+ mDC in peritumoral dermis in
RTR might contribute to impaired immunosurveillance thus giving rise to an
increased risk to develop aggressive SCC in these patients.
PMID- 25845702
TI - Histidine-modified organic-silica hybrid monolithic column for mixed-mode per
aqueous and ion-exchange capillary electrochromatography.
AB - A novel organic-silica hybrid monolith was prepared through the binding of
histidine onto the surface of monolithic matrix for mixed-mode per aqueous and
ion-exchange capillary electrochromatography. The imidazolium and amino groups on
the surface of the monolithic stationary phase were used to generate an anodic
electro-osmotic flow as well as to provide electrostatic interaction sites for
the charged compounds at low pH. Typical per aqueous chromatographic behavior was
observed in water-rich mobile phases. Various polar and hydrophilic analytes were
selected to evaluate the characteristics and chromatographic performance of the
obtained monolith. Under per aqueous conditions, the mixed-mode mechanism of
hydrophobic and ion-exchange interactions was observed and the resultant
monolithic column proved to be very versatile for the efficient separations of
these polar and hydrophilic compounds (including amides, nucleosides and
nucleotide bases, benzoic acid derivatives, and amino acids) in highly aqueous
mobile phases. The successful applications suggested that the histidine-modified
organic-silica hybrid monolithic column could offer a wide range of retention
behaviors and flexible selectivities toward polar and hydrophilic compounds.
PMID- 25845703
TI - The early Pleistocene deciduous hominid molar FS-72 from the Sangiran Dome of
Java, Indonesia: A taxonomic reappraisal based on its comparative endostructural
characterization.
AB - OBJECTIVES: Among the ten fossil hominid deciduous teeth reported so far from the
Pleistocene sediments of the Sangiran Dome of Java are two isolated lower second
molars: specimens PCG.2 from the Kabuh Formation and FS-72 from the Pucangan
Formation. While PCG.2 appears to be certainly attributable to Homo erectus, FS
72 is somewhat more problematic, even though it is commonly listed within the
Indonesian H. erectus hypodigm. Largely because of its large size, it was
originally attributed to Meganthropus paleojavanicus. Subsequent study
highlighted a set of metric and nonmetric crown features also found in
Australopith and African early Homo (notably H. habilis) homologues. An
additional problem with the taxonomic assignment of isolated teeth from the
Pleistocene of Java is the presence of Pongo in these same deposits. METHODS: To
assess the taxonomic affinity of FS-72, we investigated its inner structure
(tissue proportions and enamel-dentine junction morphology) by using techniques
of 2-3D virtual imaging coupled with geometric morphometric analyses. RESULTS:
The results show that FS-72 has thinner enamel compared to fossil and recent
humans and that its topographic repartition more closely follows the pongine
pattern. It also exhibits a Pongo-like elongated morphology of the enamel-dentine
junction, with proportionally lower and mesiodistally spaced dentine horns.
CONCLUSIONS: Given the morphological and metric similarities between fossil
orangutan and H. erectus molars, we tested the hypothesis that its internal
morphology more closely resembles the patterns evinced by PCG.2 and modern humans
than Pongo. Accordingly, we consider that FS-72 more likely represents a dm2 of
Pongo rather than Homo.
PMID- 25845704
TI - D-dimers Are a Predictor of Clot Volume Inside Membrane Oxygenators During
Extracorporeal Membrane Oxygenation.
AB - Thrombosis inside the membrane oxygenator (MO) is a critical complication during
venovenous extracorporeal membrane oxygenation (ECMO). The aim of this study was
to prove if thrombotic clots manifest within the MO when D-dimer levels are
elevated over a long-term period. Heparin-coated polymethylpentene MOs (n = 13)
were exchanged due to high plasma D-dimer levels. Clot volume was calculated
using multidetector computed tomography (MDCT). Coagulation parameters and MO
function were analyzed before and after MO exchange. Before MO exchange, D-dimer
levels increased significantly in each patient (11.5 [6.5-15.5] mg/L to 35.0 [34
35] mg/L, P <= 0.001). High levels of D-dimers were tolerated for 1 to 6 days.
Additionally, fibrinogen concentration (n = 8) and platelet count decreased (n =
8). Within 48 h after exchange, D-dimer levels decreased significantly (n = 11,
12 [8-16] mg/L, P = 0.004). Fibrinogen concentration and platelet counts
increased. Clots were found in all MOs in the inlet part of the device. Clot
volume (16-106 cm(3) ) did not correlate with MO support time but increased
significantly when high D-dimer levels were accepted for >2 days. An increase or
high levels of D-dimers in absence of other explaining pathology during ECMO
therapy reflected coagulation activity within the MO. Evidence of clots within
the MO at high D-dimer levels and decrease after exchange underline the relevance
of D-dimer testing during ECMO treatment. Besides, surveillance of MOs during
ongoing ECMO therapy will help to predict clot formation, and to avoid system
induced coagulation disorders as well as critical situations.
PMID- 25845706
TI - Strongly bias-dependent tunnel magnetoresistance in manganite spin filter tunnel
junctions.
AB - A highly unconventional bias-dependent tunnel magnetoresistance (TMR) response is
observed in Sm0.75 Sr0.25 MnO3 -based nanopillar spin filter tunnel junctions
(SFTJs) with two different behaviors in two different thickness regimes of the
barrier layer. Thinner barrier devices exhibit conventional SFTJ behaviors;
however, for larger barrier thicknesses, the TMR-bias dependence is more complex
and reverses sign at higher bias.
PMID- 25845705
TI - Measurement of 25-hydroxyvitamin D(2&3) and 1,25-dihydroxyvitamin D(2&3) by
tandem mass spectrometry: A primate multispecies comparison.
AB - Vitamin D metabolites are widely studied for their roles in bone health, immune
functions, and other potential physiologic roles in humans. However, the optimal
blood levels of vitamin D metabolites are still unclear. Various methods for
measuring vitamin D metabolites have been used and recently liquid chromatography
tandem mass spectroscopy (LC-MS/MS) has been adopted as the gold standard for
vitamin D metabolite measurement. Here, we report the use of LC-MS/MS to measure
25-hydroxyvitamin D (25(OH)D(2&3)), and 1,25-dihydroxyvitamin D
(1,25(OH)2D(2&3)), in three laboratory nonhuman primate species: common marmoset
(Callithrix jacchus), rhesus macaque (Macaca mulatta), and cynomolgus macaque
(Macaca fascicularis), and compare them to humans using the same technique. The
nonhuman primates showed blood levels for 25(OH)D3 and 1,25(OH)2D3 significantly
higher than human values with marmosets having the highest levels. Marmoset
samples showed significantly more variability among individuals than those from
macaques for both metabolites, but all three nonhuman primate species exhibited
large variation within species for both 25(OH)D(2&3) and 1,25(OH)2D(2&3).
Marmoset females had significantly lower values than the males for 25(OH)D3,
while rhesus males showed a significant decrease in 25(OH)D3 with age. The most
striking finding is the variation within species for vitamin D levels even in
laboratory primates that have a controlled diet, UV exposure, and in some cases,
genetic constraints. Similar variation in 25(OH)D responses to a fixed dose of
oral vitamin D supplementation has been reported in humans. We suggest that these
species can provide primate models for examining the factors influencing
variation in the levels of vitamin D necessary for human and nonhuman primate
health.
PMID- 25845707
TI - Spinal cord neuron inputs to the cuneate nucleus that partially survive dorsal
column lesions: A pathway that could contribute to recovery after spinal cord
injury.
AB - Dorsal column lesions at a high cervical level deprive the cuneate nucleus and
much of the somatosensory system of its major cutaneous inputs. Over weeks of
recovery, much of the hand representations in the contralateral cortex are
reactivated. One possibility for such cortical reactivation by hand afferents is
that preserved second-order spinal cord neurons reach the cuneate nucleus through
pathways that circumvent the dorsal column lesions, contributing to cortical
reactivation in an increasingly effective manner over time. To evaluate this
possibility, we first injected anatomical tracers into the cuneate nucleus and
plotted the distributions of labeled spinal cord neurons and fibers in control
monkeys. Large numbers of neurons in the dorsal horn of the cervical spinal cord
were labeled, especially ipsilaterally in lamina IV. Labeled fibers were
distributed in the cuneate fasciculus and lateral funiculus. In three other
squirrel monkeys, unilateral dorsal column lesions were placed at the cervical
segment 4 level and tracers were injected into the ipsilateral cuneate nucleus.
Two weeks later, a largely unresponsive hand representation in contralateral
somatosensory cortex confirmed the effectiveness of the dorsal column lesion.
However, tracer injections in the cuneate nucleus labeled only about 5% of the
normal number of dorsal horn neurons, mainly in lamina IV, below the level of
lesions. Our results revealed a small second-order pathway to the cuneate nucleus
that survives high cervical dorsal column lesions by traveling in the lateral
funiculus. This could be important for cortical reactivation by hand afferents,
and recovery of hand use.
PMID- 25845708
TI - Prospective study of Helicobacter pylori antigens and gastric noncardia cancer
risk in the nutrition intervention trial cohort.
AB - Helicobacter pylori (H. pylori) infection is the strongest known risk factor for
gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine
whether seropositivity to 15 H. pylori proteins is associated with the subsequent
development of noncardia gastric cancer in Linxian, China. We included 448 GNCA
cases and 1242 controls from two time points within the Linxian General
Population Nutrition Intervention Trial, Linxian. H. pylori multiplex
seropositivity was defined as positivity to >=4 of the 15 included antigens. Odds
ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk
factors. In addition, we undertook a meta-analysis combining H. pylori multiplex
serology data from both time points. H. pylori multiplex seropositivity was
associated with a significant increase in risk of GNCA at one time point (1985;
OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following
adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56,
5.47). Combining data from both time points in a meta-analysis H. pylori
multiplex seropositivity was associated with an increased risk of GNCA, as were
six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was
inversely associated with risk of GNCA. We identified six individual antigens
that confer an increase in risk of GNCA within this population of high H. pylori
seroprevalence, as well as a single antigen that may be inversely associated with
GNCA risk. We further determined that the H. pylori multiplex assay provides
additional information to the conventional ELISA methods on risk of GNCA.
PMID- 25845709
TI - Impact of quality improvement measures on the delivery of allergy immunotherapy:
a 2-year follow-up.
AB - BACKGROUND: Anaphylaxis is the most serious potential complication from allergy
treatment with subcutaneous immunotherapy (SCIT). Quality measures were developed
with the goal to decrease the incidence of complications resulting from SCIT and
improve the safety of care provided. METHODS: The incidence and characteristics
of anaphylaxis episodes resulting from SCIT was measured between 2008 and 2012
prior to implementation of quality measures including vial verification, vial
testing, and standardized training across 6 allergy delivery sites. Errors and
anaphylaxis rates were then tracked prospectively over a 2-year period after
implementation of these process measures. RESULTS: From 2008 to 2012 there were 9
episodes of anaphylaxis or 0.02% of injections/year. Eight patients had
sufficient information from which to derive meaningful data. Patient
identification error led to anaphylaxis in 2 patients, dosing error in 2, and
compounding error in 1 patient. In 2 patients, anaphylaxis occurred with
advancement during pollen season, and in 1 patient no clear reason could be
identified although she had asthma as a risk factor. After implementation of
quality improvement measures the anaphylaxis rate fell to 0 of 8948 injections
for years 2013 and 2014. CONCLUSION: Errors in the mixing and administration of
allergy serum comprised the majority of identifiable factors that led to
anaphylaxis. Implementation of quality measures, including vial verification and
vial testing, can improve safety and decrease anaphylaxis rates in the delivery
of allergy immunotherapy.
PMID- 25845710
TI - APPROXIMATING A DSM-5 DIAGNOSIS OF PTSD USING DSM-IV CRITERIA.
AB - BACKGROUND: Diagnostic criteria for DSM-5 posttraumatic stress disorder (PTSD)
are in many ways similar to DSM-IV criteria, raising the possibility that it
might be possible to closely approximate DSM-5 diagnoses using DSM-IV symptoms.
If so, the resulting transformation rules could be used to pool research data
based on the two criteria sets. METHODS: The pre-post deployment study (PPDS) of
the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)
administered a blended 30-day DSM-IV and DSM-5 PTSD symptom assessment based on
the civilian PTSD Checklist for DSM-IV (PCL-C) and the PTSD Checklist for DSM-5
(PCL-5). This assessment was completed by 9,193 soldiers from three US Army
Brigade Combat Teams approximately 3 months after returning from Afghanistan. PCL
C items were used to operationalize conservative and broad approximations of DSM
5 PTSD diagnoses. The operating characteristics of these approximations were
examined compared to diagnoses based on actual DSM-5 criteria. RESULTS: The
estimated 30-day prevalence of DSM-5 PTSD based on conservative (4.3%) and broad
(4.7%) approximations of DSM-5 criteria using DSM-IV symptom assessments were
similar to estimates based on actual DSM-5 criteria (4.6%). Both approximations
had excellent sensitivity (92.6-95.5%), specificity (99.6-99.9%), total
classification accuracy (99.4-99.6%), and area under the receiver operating
characteristic curve (0.96-0.98). CONCLUSIONS: DSM-IV symptoms can be used to
approximate DSM-5 diagnoses of PTSD among recently deployed soldiers, making it
possible to recode symptom-level data from earlier DSM-IV studies to draw
inferences about DSM-5 PTSD. However, replication is needed in broader trauma
exposed samples to evaluate the external validity of this finding.
PMID- 25845711
TI - Increased risk of portal vein thrombosis in patients with cirrhosis due to
nonalcoholic steatohepatitis.
AB - Portal vein thrombosis (PVT) is a common complication of cirrhosis sometimes
implicated in hepatic decompensation. There are no consistent epidemiologic data
to suggest an increased risk of thrombotic complications in nonalcoholic
steatohepatitis (NASH); however, research suggests an increased risk of
thrombosis. Our aim was to examine the independent association between NASH
cirrhosis and PVT in patients who underwent liver transplantation (LT) in a cross
sectional study. Data on all LTs occurring in the United States between January
1, 2003 and December 31, 2012 were obtained from the United Network for Organ
Sharing. Multivariable models were constructed to assess the statistical
associations and risk factors for the development of PVT. A total of 33,368
patients underwent transplantation. Of these, 2096 (6.3%) had PVT. Of the
patients with PVT, 12.0% had NASH. When we compared these patients to a composite
of all other causes of cirrhosis, an increased prevalence of PVT was again found,
with 10.1% having PVT at the time of transplantation versus 6.0% without NASH (P
< 0.001). The strongest risk factor independently associated with a diagnosis of
PVT in a multivariable analysis was NASH cirrhosis (odds ratio, 1.55; 95%
confidence interval, 1.33-1.81; P < 0.001). NASH cirrhosis appears to predispose
a patient to PVT independently of other risk factors. These epidemiological
findings provide support for the idea that NASH is a prothrombotic state, and
they should lead to more research in treatment and prevention in this population.
PMID- 25845712
TI - 12q21.2q22 deletion: a new patient.
AB - Interstitial deletions of long arm of chromosome 12 are rare, and the
interstitial deletion 12q21.1q22 has been reported to the best of our knowledge
in only four patients. Comparing the patients reported, a characteristic
phenotypic pattern (facial features like prominent forehead, short and upturned
nose, low set ears, and ectodermal abnormalities) can be identified. It has been
suggested to be considered a deletion syndrome [Klein et al., (2005); Am J Med
Genet 138:349-354]. We report on a 34-month-old girl, who was referred to our
clinic at 6 months of age, presenting at birth with axial hypotonia, enlarged
anterior fontanel, ventriculomegaly, dysmorphic facies (prominent forehead,
sparse hair and eyebrows, short palpebral fissures), failure to thrive and
development delay. Her cytogenetic study showed an interstitial deletion of the
long arm of chromosome 12: 46,XX,del(12)(q21.1q22) redefined by array comparative
genomic hybridization. We compare and review our patient with the four previously
reported cases, plus one with a deletion with an overlap of the chromosomal
region and phenotypic similarities. As far as we know our patient is the fourth
reported with this cytogenetic abnormality. This additional report allows us to
support a genotype-phenotype correlation for this chromosomal abnormality.
PMID- 25845713
TI - Sensitivity of chemical shift-encoded fat quantification to calibration of fat MR
spectrum.
AB - PURPOSE: To evaluate the impact of different fat spectral models on proton
density fat fraction quantification using chemical shift-encoded MRI (CSE-MRI).
METHODS: In a simulation study, spectral models of fat were compared pairwise.
Comparison of magnitude fitting and mixed fitting was performed over a range of
echo times and fat fractions. In vivo acquisitions from 41 patients were
reconstructed using seven published spectral models of fat. T2-corrected
stimulated echo acquisition mode MR spectroscopy was used as a reference.
RESULTS: The simulations demonstrated that imperfectly calibrated spectral models
of fat result in biases that depend on echo times and fat fraction. Mixed fitting
was more robust against this bias than magnitude fitting. Multipeak spectral
models showed much smaller differences among themselves than from the single-peak
spectral model. In vivo studies showed that all multipeak models agreed better
(for mixed fitting, the slope ranged from 0.967 to 1.045 using linear regression)
with the reference standard than the single-peak model (for mixed fitting, slope
= 0.76). CONCLUSION: It is essential to use a multipeak fat model for accurate
quantification of fat with CSE-MRI. Furthermore, fat quantification techniques
using multipeak fat models are comparable, and no specific choice of spectral
model has been shown to be superior to the rest.
PMID- 25845714
TI - Off-label use of nicardipine as tocolytic and acute pulmonary oedema: a post
marketing analysis of adverse drug reaction reports in EudraVigilance.
AB - PURPOSE: To evaluate a signal of acute pulmonary oedema (APO) due to nicardipine
used off-label as tocolytic in pregnant women. METHODS: All the suspected cases
of APO recorded in EudraVigilance database up to 31/01/2013 and associated with
nicardipine containing medicinal products were retrieved. The Proportional
Reporting Ratio was considered as measure of disproportionality. Individual cases
evaluation was conducted. RESULTS: Thirty-four spontaneous cases regarding
pregnancy women who experienced APO following nicardipine treatment as tocolytic
were collected. The detected proportional reporting ratio was 50.96 (95%
confidence interval lower bound equal to 36.75). The analysis focused on 10
serious cases. Most women, aged between 27 and 39 years, were treated with
intravenous nicardipine. The most of the suspected adverse reactions occurred
between 24 and 96 hours. CONCLUSIONS: A potentially causal association between
APO and off-label use of nicardipine as tocolytic has been detected during a
periodic signal detection activity. The Pharmacovigilance Risk Assessment
Committee confirmed our findings, recommending an update of the summary of the
product characteristics for medicines containing nicardipine for both intravenous
and oral formulations. Then European Medicines Agency reaffirmed that nicardipine
use in other indications is no longer recommended.
PMID- 25845715
TI - Endovascular Therapy for Acute Ischemic Stroke: Time to Enter a New Era in Stroke
Management.
PMID- 25845716
TI - Omega-3 eicosatetraenoic acid production by molecular breeding of the mutant
strain S14 derived from Mortierella alpina 1S-4.
AB - We investigated the omega-3 eicosatetraenoic acid (ETA) production by molecular
breeding of the oleaginous fungus Mortierella alpina, which can slightly
accumulate ETA only when cultivated at a low temperature. The endogenous omega3
desaturase gene or the heterologous Saprolegnia diclina Delta17 (sdd17m)
desaturase gene were overexpressed in M. alpina S14, a Delta5-desaturation
activity-defective mutant derived from M. alpina 1S-4. M. alpina S14
transformants introduced with the endogenous omega3-desaturase gene showed ETA at
42.1% content in the total lipids that was 84.2-fold and 3.2-fold higher than
that of the wild-type strain 1S-4 and host strain S14, respectively, when
cultivated at 12 degrees C. No accumulation of ETA was observed at 28 degrees C.
In contrast, transformants with the heterologous sdd17m gene showed 24.9% of the
content of total lipids at 28 degrees C. These results indicated that these M.
alpina S14 transformants are promising strains for the production of ETA, which
is hard to obtain from natural sources.
PMID- 25845717
TI - Systematic identification of thermal degradation products of HPMCP during hot
melt extrusion process.
AB - A systematic identification of the degradation products of hydroxypropyl
methylcellulose phthalate (HPMCP) during hot melt extrusion (HME) has been
performed. A reverse phase HPLC method was developed for the extrudates of both
hydroxypropyl methylcellulose acetate succinate (HPMCAS) and HPMCP polymers to
quantify their thermal hydrolytic products: acetic acid (AA), succinic acid (SA)
for HPMCAS and phthalic acid (PA) for HPMCP, without hydrolysing the polymers in
strong alkaline solutions. The polymers were extruded in the temperature range of
160-190 degrees C at different screw rotation speeds and hydrolytic impurities
were analysed. Investigation of extruded HPMCP showed an additional thermal
degradation product, who is structural elucidation revealed to be phthalic
anhydride (PAH). Moreover, two environmental analytical impurities, dimethyl
phthalate and methyl benzoate formed in situ were recorded on GC-MS and their
origin was found to be associated with PAH derivatization. Using the experimental
data gathered during this study, a degradation mechanism for HPMCP is proposed.
PMID- 25845718
TI - DEM analysis of the effect of particle-wall impact on the dispersion performance
in carrier-based dry powder inhalers.
AB - The impact between particles or agglomerates and a device wall is considered as
an important mechanism controlling the dispersion of active pharmaceutical
ingredient (API) particles in dry powder inhalers (DPIs). In order to
characterise the influencing factors and better understand the impact induced
dispersion process for carrier-based DPIs, the impact behaviour between an
agglomerate and a wall is systematically investigated using the discrete element
method. In this study, a carrier-based agglomerate is initially formed and then
allowed to impact with a target wall. The effects of impact velocity, impact
angle and work of adhesion on the dispersion performance are analysed. It is
shown that API particles in the near-wall regions are more likely to be dispersed
due to the deceleration of the carrier particle resulted from the impact with the
wall. It is also revealed that the dispersion ratio increases with increasing
impact velocity and impact angle, indicating that the normal component of the
impact velocity plays a dominant role on the dispersion. Furthermore, the impact
induced dispersion performance for carrier-based DPI formulations can be well
approximated using a cumulative Weibull distribution function that is governed by
the ratio of overall impact energy and adhesion energy.
PMID- 25845719
TI - Risk assessment of nanoformulations.
PMID- 25845721
TI - Physiological effects of polybrominated diphenyl ether (PBDE-47) on pregnant
gartersnakes and resulting offspring.
AB - Polybrominated diphenyl ethers (PBDEs) are used as flame retardants and are
persistent contaminants found in virtually every environment and organism sampled
to date, including humans. There is growing evidence that PBDEs are the source of
thyroid, neurodevelopmental, and reproductive toxicity. Yet little work has
focused on how this pervasive contaminant may influence the reproduction and
physiology of non-traditional model species. This is especially critical because
in many cases non-model species, such as reptiles, are most likely to come into
contact with PBDEs in nature. We tested how short-term, repeated exposure to the
PBDE congener BDE-47 during pregnancy affected physiological processes in
pregnant female gartersnakes (thyroid follicular height, bactericidal ability,
stress responsiveness, reproductive output, and tendency to terminate pregnancy)
and their resulting offspring (levels of corticosterone, bactericidal ability,
and size differences). We found potential effects of BDE-47 on both the mother,
such as increased size and higher thyroid follicular height, and her offspring
(increased size), suggesting the effects on physiological function of PBDEs do
indeed extend beyond the traditional rodent models.
PMID- 25845720
TI - A novel in vitro assay for assessing efficacy and toxicity of antifungals using
human leukaemic cells infected with Candida albicans.
AB - AIMS: This study describes a novel in vitro assay that simultaneously determines
antifungal efficiency and host cell toxicity using suspensions of human leukaemic
cells (HL-60) infected with Candida albicans. METHODS AND RESULTS: The effect of
Candida infection on host cell viability was evaluated by the microscopy of
trypan blue-stained cells and lactate dehydrogenase (LDH) activity. The in vitro
'drug potency assay' utilized the Cell Counting Kit-8 and measured post
antifungal treatment viability of Candida-infected HL-60 cells and the ability of
the antifungal treatment to prevent infection. LDH activity showed that 42% +/-
4.0 and 85.3% +/- 7.40 of HL-60 cells were killed following Candida infection at
the multiplicity of infection (MOI) of 1 : 1 and 1 : 5, respectively. The
antifungal nystatin (0.78-25 MUmol l(-1) ) was found to inhibit C. albicans
infection as seen by the significantly increased viability of HL-60 cells.
Cytotoxicity of nystatin towards infected HL-60 cells was evident at higher
concentrations and this was also confirmed by propidium iodide staining.
CONCLUSIONS: An assay using undisturbed cell suspension conditions was
successfully developed for assessing the selectivity of the antifungal therapy in
the host-Candida environment. SIGNIFICANCE AND IMPACT OF THE STUDY: The assay
employing Candida infection of host cell suspensions represents a promising
method for testing interactions of antifungal compounds with both fungal and host
cells.
PMID- 25845722
TI - Rice endosperm produces an underglycosylated and potent form of the HIV
neutralizing monoclonal antibody 2G12.
AB - Protein microbicides against HIV can help to prevent infection but they are
required in large, repetitive doses. This makes current fermenter-based
production systems prohibitively expensive. Plants are advantageous as production
platforms because they offer a safe, economical and scalable alternative, and
cereals such as rice are particularly attractive because they could allow
pharmaceutical proteins to be produced economically and on a large scale in
developing countries. Pharmaceutical proteins can also be stored as unprocessed
seed, circumventing the need for a cold chain. Here, we report the development of
transgenic rice plants expressing the HIV-neutralizing antibody 2G12 in the
endosperm. Surprisingly for an antibody expressed in plants, the heavy chain was
predominantly aglycosylated. Nevertheless, the heavy and light chains assembled
into functional antibodies with more potent HIV-neutralizing activity than other
plant-derived forms of 2G12 bearing typical high-mannose or plant complex-type
glycans. Immunolocalization experiments showed that the assembled antibody
accumulated predominantly in protein storage vacuoles but also induced the
formation of novel, spherical storage compartments surrounded by ribosomes
indicating that they originated from the endoplasmic reticulum. The comparison of
wild-type and transgenic plants at the transcriptomic and proteomic levels
indicated that endogenous genes related to starch biosynthesis were down
regulated in the endosperm of the transgenic plants, whereas genes encoding
prolamin and glutaredoxin-C8 were up-regulated. Our data provide insight into
factors that affect the functional efficacy of neutralizing antibodies in plants
and the impact of recombinant proteins on endogenous gene expression.
PMID- 25845723
TI - Surveillance versus clinical adjudication: differences persist with new
ventilator-associated event definition.
AB - BACKGROUND: The National Healthcare Safety Network (NHSN) has recently supported
efforts to shift surveillance away from ventilator-associated pneumonia to
ventilator-associated events (VAEs) to decrease subjectivity in surveillance and
minimize concerns over clinical correlation. The goals of this study were to
compare the results of an automated surveillance strategy using the new VAE
definition with a prospectively performed clinical application of the definition.
METHODS: All patients ventilated for >=2 days in a medical and surgical intensive
care unit were evaluated by 2 methods: retrospective surveillance using an
automated algorithm combined with manual chart review after the NHSN's VAE
methodology and prospective surveillance by pulmonary physicians in collaboration
with the clinical team administering care to the patient at the bedside. RESULTS:
Overall, a similar number of events were called by each method (69 vs 67). Of the
1,209 patients, 56 were determined to have VAEs by both methods (kappa = .81, P =
.04). There were 24 patients considered to be a VAE by only 1 of the methods.
Most discrepancies were the result of clinical disagreement with the NHSN's VAE
methodology. CONCLUSIONS: There was good agreement between the study teams.
Awareness of the limitations of the surveillance definition for VAE can help
infection prevention personnel in discussions with critical care partners about
optimal use of these data.
PMID- 25845724
TI - Contributing factors to star excursion balance test performance in individuals
with chronic ankle instability.
AB - The purpose of this study was to determine the contributions of strength,
dorsiflexion range of motion (DFROM), plantar cutaneous sensation (PCS), and
static postural control to Star Excursion Balance Test (SEBT) performance in
individuals with chronic ankle instability (CAI). Forty individuals with CAI
completed isometric strength, weight-bearing DFROM, PCS, static and dynamic
balance assessments. Three separate backward multiple linear regression models
were calculated to determine how strength, DFROM, PCS, and static postural
control contributed to each reach direction of the SEBT. Explanatory variables
included dorsiflexion, inversion, and eversion strength, DFROM, PCS, and time-to
boundary mean minima (TTBMM) and standard deviation (TTBSD) in the medial-lateral
(ML) and anterior-posterior (AP) directions. Criterion variables included SEBT
anterior, posteromedial, and posterolateral directions. The strength of each
model was determined by the R2-value and Cohen's f2 effect size. Regression
models with an effect size >=0.15 were considered clinically relevant. All three
SEBT directions produced clinically relevant regression models. DFROM and PCS
accounted for 16% of the variance in SEBT-anterior reach (f2=0.19, p=0.04).
Eversion strength and TTBMM-ML accounted for 28% of the variance in SEBT
posteromedial reach (f2=0.39, p<0.01). Eversion strength and TTBSD-ML accounted
for 14% of the variance in SEBT-posterolateral reach (f2=0.16, p=0.06). DFROM and
PCS explained a clinically relevant proportion of the variance associated with
SEBT-anterior reach. Eversion strength and TTB ML explained a clinically relevant
proportion of the variance in SEBT-posteromedial and posterolateral reach
distances. Therefore, rehabilitation strategies should emphasize DFROM, PCS,
eversion strength, and static balance to enhance dynamic postural control in
patients with CAI.
PMID- 25845733
TI - Fine structure of the male genital system of the predatory mite Rhagidia
halophila (Rhagidiidae, Prostigmata, Actinotrichida).
AB - The male genital system of the actinotrichid mite Rhagidia halophila is described
and compared with other mites and arachnids. The large testes are composed of
germinal and glandular parts and produce numerous small sperm cells. The
glandular parts are connected via a testicular bridge. Spermiogenesis occurs in
cysts containing spermatids in equal stages of development. Cysts of spermatids
are embedded in huge somatic cells. The nuclei of the spermatids loose their
envelope. Mature sperm cells are simple exhibiting a ring-shaped chromatin body
and lacking an acrosomal complex. They are most similar to the sperm cells of the
related mite Linopodes motatorius. The spermatopositor contains the ejaculatory
duct divided into a dorsal channel and a ventral channel that are connected via a
narrow passage. At its distal end, the spermatopositor is divided into three
eugenital lips. The function of the spermatopositor during deposition of the
peculiar thread-like spermatophores is discussed. Details of the sensilla of the
spermatopositor and the progenital lips are reported. The genital papillae
located on the inner side of the progenital lips exhibit characteristics of cells
performing transport of ions and/or water. The results confirm the overall
similarity of actinotrichid genital systems, which is profoundly different from
that of anactinotrichid mites. With reference to other Arachnida it is
corroborated that testes and sperm structure of Actinotrichida are most similar
to that of Solifugae. However, synapomorphies between sperm cells of Rhagidia and
Solifugae that could suggest a closer relationship between these two taxa as was
suggested in earlier studies were not recognizable. On the contrary, the sperm
cells of Rh. halophila being devoid of an acrosomal complex appeared to be more
apomorphic than those of many other actinotrichid mites as well as Solifugae.
PMID- 25845734
TI - Parents' experiences when their child is undergoing an elective colonoscopy.
AB - PURPOSE: The purpose was to illuminate parents' experiences when their children
are undergoing an elective colonoscopy performed using polyethylene glycol-based
regimes for bowel preparation. DESIGN AND METHODS: Individual interviews with 12
parents were performed and analysed using content analysis. RESULTS: The parents'
experiences were structured into one theme: "Charged with conflicting emotions"
with three categories: "Being forced to force," "Losing one's sense of being a
parent" and "Standing without guidance." PRACTICE IMPLICATIONS: Understanding
parents' experiences can help healthcare staff guide parents in helping their
children undergo a colonoscopy.
PMID- 25845735
TI - rRNA regulation during growth and under stringent conditions in Staphylococcus
aureus.
AB - The control of rRNA synthesis and, thereby, translation is vital for adapting to
changing environmental conditions. The decrease of rRNA is a common feature of
the stringent response, which is elicited by the rapid synthesis of (p)ppGpp.
Here we analysed the properties and regulation of one representative rRNA operon
of Staphylococcus aureus under stringent conditions and during growth. The
promoters, P1 and P2, are severely downregulated at low intracellular guanosine
triphosphate (GTP) concentrations either imposed by stringent conditions or in a
guanine auxotroph guaBA mutant. In a (p)ppGpp(0) strain, the GTP level increased
under stringent conditions, and rRNA transcription was upregulated. The
correlation of the intracellular GTP levels and rRNA promoter activity could be
linked to GTP nucleotides in the initiation region of both promoters at positions
between +1 and +4. This indicates that not only transcriptional initiation, but
also the first steps of elongation, requires high concentrations of free
nucleotides. However, the severe downregulation of rRNA in post-exponential
growth phase is independent of (p)ppGpp, the composition of the initiation region
and the intracellular nucleotide pool. In summary, rRNA transcription in S.
aureus is only partially and presumably indirectly controlled by (p)ppGpp.
PMID- 25845736
TI - Support for down-staging of pregnancy-associated cervical cancer.
AB - OBJECTIVE: To evaluate all cases of cervical cancer associated with pregnancy
during 16 years in the Western Region of Sweden. DESIGN: Retrospective,
descriptive cohort study. SETTING AND POPULATION: All women with cervical cancer,
diagnosed during pregnancy or within 6 months after parturition, between 1993 and
2008. METHODS: The study was based on data from different registers and medical
records. MAIN OUTCOME MEASURES: Incidence, diagnostic measures, treatment and
outcome of disease. RESULTS: Cervical cancer was diagnosed in 47 women (15.6/100
000 deliveries). Sixteen women had abnormal vaginal bleeding and/or discharge.
The other women were asymptomatic and diagnosed by abnormal cervical smear or
clinical signs at vaginal examination. Nine women had atypical squamous cells of
uncertain significance as presenting by cervical atypia. Twenty-two women had
stage IA, 17 stage IB1, six stage IB2 and two stage IIA cancer. Cancer was
diagnosed in the first trimester in two, in the second trimester in 14, in the
third trimester in five and postpartum in 26 women. Histology revealed squamous
cell carcinoma in 36 women, adenocarcinoma in eight, and adenosquamous carcinoma
in three. Twenty women underwent cesarean section due to diagnosed or clinically
suspected cancer, combined with the Wertheim-Meigs radical hysterectomy in six
women. Sixteen women with stage IA1 cancer without signs of vascular invasion
underwent conization as definitive therapy. Six women died of the disease.
CONCLUSION: Early detection of cervical cytological atypia and proper follow-up
during pregnancy led to detection of a high proportion of stage I cancer cases,
which could be cured with fertility-sparing therapy.
PMID- 25845737
TI - Complex assessment of distinct cognitive impairments following ouabain injection
into the rat dorsoloateral striatum.
AB - A stroke in humans may induce focal injury to the brain tissue resulting in
various disabilities. Although motor deficits are the most discernible, cognitive
impairments seem to be crucial for patients mental well-being. The current lack
of effective treatments encourages scientists and clinicians to develop novel
approaches. Before applying them in clinic, testing for safety and effectiveness
in non-human models is necessary. Such animal model should include significant
cognitive impairments resulting from brain lesion. We used ouabain stereotactic
injection into the right dorsolateral striatum of male Wistar rats, and enriched
environment housing. To confirm the brain injury before cognitive testing, rats
were given a beam-walking task to evaluate the level of sensorimotor deficits. To
determine the cognitive impairment after focal brain damage, rats underwent a set
of selected tasks over an observation period of 30 days. Brain injury induced by
ouabain significantly impaired the acquisition of the T-maze habit learning task,
where 'win-stay' strategy rules were applied. The injured rats also showed
significant deficits in the performance of the T-maze switching task, which
involved shifting from multiple clues previously relevant to the only one
important clue. Focal brain injury also significantly changed 'what--where'
memory, tested in the object exploration task, in which a novel object
consecutively appeared in the same place while the location of a familiar item
was continuously changed. In conclusion, we developed an animal model of distinct
cognitive impairments after focal brain injury that provides a convenient method
to test the effectiveness of restorative therapies.
PMID- 25845738
TI - Studies on the animal model of post-stroke depression and application of
antipsychotic aripiprazole.
AB - We investigated the question of whether an animal model of post-stroke depression
in ischemic stroke can be developed by additional chronic mild stress (CMS)
procedures. Behavioral and histopathological analysis was performed for
examination of the depressive disorders in CMS, left middle cerebral artery
occlusion (MCAO) and CMS after MCAO (MCAO+CMS) in mice. In all depressant
screening tests involving open field, sucrose preference, forced swim and Morris
water maze test, MCAO+CMS mice showed more significant depressive behaviors than
MCAO mice. MCAO+CMS mice also showed distinct deficits in forced swim and Morris
water maze test compared with CMS. In the histopathological analysis, prominent
atrophic changes were seen in the striatum and midbrain of MCAO treated mice
compared with CMS. MCAO+CMS mice showed a decrease of proliferative and
differentiated neuronal cells in the striatum and hippocampus with dopaminergic
neuronal injuries in the midbrain as compared with CMS and MCAO alone treated
mice. Treatment of MCAO+CMS mice with aripiprazole resulted in reduction of all
depressive behaviors examined, particularly in the Morris water maze test.
Recovered dopaminergic neuronal injuries in the midbrain and enhanced
neurogenesis in the hippocampus were also demonstrated. Our results suggest that
CMS after ischemic stroke can lead to severe depressive-like behavior compared
with CMS or MCAO alone treated mice via neurodegeneration in the primary lesion
and secondary extrafocal sites and degradation of neurogenesis, and these
behavioral and histopathological changes are reversed by treatment with
aripiprazole. Thus adjunct therapy with an antipsychotic may exert its
antidepressant effects via neuroprotection and neurogenesis in CMS-treated
ischemic mice.
PMID- 25845740
TI - Gene-environment interaction of reelin and stress in cognitive behaviours in
mice: Implications for schizophrenia.
AB - Cognitive deficits are a particularly debilitating symptom group in
schizophrenia. We investigated the effect of a 'two hit' combination of two
factors implicated in schizophrenia development, reelin deficiency and stress, on
cognitive behaviours in mice. Male and female heterozygous reelin mice (HRM) and
wild-type (WT) controls received the stress hormone, corticosterone (CORT),
during early adulthood to simulate chronic stress. The Y-maze, novel object
recognition task (NORT), social interaction task and prepulse inhibition (PPI)
were used to assess short-term spatial memory, visual non-spatial memory, social
recognition memory and sensory gating, respectively. Reelin protein expression
was measured in the prefrontal cortex (PFC) and hippocampus. CORT induced spatial
memory deficits in male and female HRM but not in WT controls suggesting
increased vulnerability of HRM to the effects of stress on cognition. By
contrast, CORT disrupted PPI only in male WT mice, but not in male HRM,
suggesting a protective role of reelin deficiency against effects of stress on
PPI. Male HRM performed worse in the social recognition memory task compared to
wild-type controls, irrespective of CORT treatment. No differences were detected
in the NORT. Reelin protein expression was increased in the PFC of female CORT
treated HRM but there were no group differences in the hippocampus. Overall,
these findings extend our understanding of the role of reelin-stress interactions
in schizophrenia.
PMID- 25845739
TI - Antidepressant activity of fluoxetine in the zinc deficiency model in rats
involves the NMDA receptor complex.
AB - The zinc deficiency animal model of depression has been proposed; however, it has
not been validated in a detailed manner. We have recently shown that depression
like behavior induced by dietary zinc restriction is associated with up
regulation of hippocampal N-methyl-d-aspartate receptor (NMDAR). Here we examined
the effects of chronic administration of a selective serotonin reuptake
inhibitor, fluoxetine (FLX), on behavioral and biochemical alterations (within
NMDAR signaling pathway) induced by zinc deficiency. Male Sprague Dawley rats
were fed a zinc adequate diet (ZnA, 50mg Zn/kg) or a zinc deficient diet (ZnD,
3mg Zn/kg) for 4 weeks. Then, FLX treatment (10mg/kg, i.p.) begun. Following 2
weeks of FLX administration the behavior of the rats was examined in the forced
swim test (FST) and the spontaneous locomotor activity test. Twenty four hours
later tissue was harvested. The proteins of NMDAR (GluN1, GluN2A and GluN2B) or
AMPAR (GluA1) subunits, p-CREB and BDNF in the hippocampus (Western blot) and
serum zinc level (TXRF) were examined. Depression-like behavior induced by ZnD in
the FST was sensitive to chronic treatment with FLX. ZnD increased levels of
GluN1, GluN2A, GluN2B and decreased pS485-GluA1, p-CREB and BDNF proteins.
Administration of FLX counteracted the zinc restriction-induced changes in serum
zinc level and hippocampal GluN1, GluN2A, GluN2B and p-CREB but not BDNF or pS845
GluA1 protein levels. This finding adds new evidence to the predictive validity
of the proposed zinc deficiency model of depression. Antidepressant-like activity
of FLX in the zinc deficiency model is associated with NMDAR complex.
PMID- 25845742
TI - Unusual myocardial late gadolinium enhancement in isolated noncompaction
cardiomyopathy.
PMID- 25845743
TI - Reply: To PMID 25250955.
PMID- 25845745
TI - Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular
redistribution of the autoantigens Ro/Sjogren's syndrome-related antigen A (SSA)
and La/SSB in salivary gland epithelial cells.
AB - The aim of this study was to examine the levels of endoplasmic reticulum (ER)
stress in minor salivary glands, to investigate the interplay between ER stress
induced autophagy and apoptosis in human salivary gland (HSG) cells and to test
the effect of ER stress-induced apoptosis on the cellular redistribution of the
two major Sjogren's syndrome (SS) autoantigens Ro/Sjogren's syndrome-related
antigen A (SSA) and La/Sjogren's syndrome-related antigen B (SSB). Minor salivary
gland biopsies from SS patients and sicca controls were examined by
immunohistochemistry for the expression of 78 kDa glucose-regulated
protein/binding immunoglobulin protein (GRP78/BiP) as an indicator of unfolded
protein response (UPR). HSG cells were treated with thapsigargin (TG) and cell
viability, autophagy and apoptosis were assessed. Immunoblot was applied to
detect the conversion of LC3I to LC3II and the protein levels of GRP78/BiP and X
box binding protein-1 (XBP-1). Apoptosis was evaluated by a single-stranded DNA
enzyme-linked immunosorbent assay (ELISA). Ro/SSA and La/SSB localization was
visualized using immunofluorescence. GRP78/BiP was expressed by acinar and ductal
epithelial cells in salivary glands of patients and sicca controls. TG treatment
induced autophagy, as indicated by enhanced protein expression of LC3II. The
protein levels of UPR marker XBP-1 were increased after TG treatment, while
GRP78/BiP levels were decreased. TG treatment resulted in induction of HSG
apoptosis. Ro/SSA and La/SSB autoantigens were localized predominantly to the
cytoplasm in resting cells, while they were redistributed to cell membrane and
blebs in the apoptotic cells. In conclusion, ER stress is activated in minor
salivary gland epithelial cells from SS patients and controls. ER stress-induced
apoptosis in HSG cells leads to cell surface and apoptotic blebs relocalization
of Ro/SSA and La/SSB autoantigens.
PMID- 25845746
TI - Differential odor sensitivity in PTSD: Implications for treatment and future
research.
AB - BACKGROUND: Given that odors enhance the retrieval of autobiographical memories,
induce physiological arousal, and trigger trauma-related flashbacks, it is
reasonable to hypothesize that odors play a significant role in the
pathophysiology of posttraumatic stress disorder (PTSD). For these reasons, this
preliminary study sought to examine self-reported, odor-elicited distress in
PTSD. METHODS: Combat veterans with (N=30) and without (N=22) PTSD and healthy
controls (HC: N=21), completed an olfactory questionnaire that provided
information on the hedonic valence of odors as well as their ability to elicit
distress or relaxation. RESULTS: Two main findings were revealed: Compared to HC,
CV+PTSD, but not CV-PTSD, reported a higher prevalence of distress to a limited
number of select odors that included fuel (p=.004), blood (p=.02), gunpowder
(p=.03), and burning hair (p=.02). In contrast to this increased sensitivity, a
blunting effect was reported by both groups of veterans compared to HC that
revealed lower rates of distress and relaxation in response to negative hedonic
odors (p=.03) and positive hedonic odors (p<.001), respectively. LIMITATIONS: The
study is limited by its use of retrospective survey methods, whereas future
investigations would benefit from laboratory measures taken prior, during, and
after deployment. CONCLUSION: The present findings suggest a complex role of
olfaction in the biological functions of threat detection. Several theoretical
models are discussed. One possible explanation for increased sensitivity to
select odors with decreased sensitivity to other odors is the co-occurrence of
attentional bias toward threat odors with selective ignoring of distractor odors.
Working together, these processes may optimize survival.
PMID- 25845747
TI - Decreased insular connectivity in drug-naive major depressive disorder at rest.
AB - BACKGROUND: The insula has extensive links to the fronto-limbic circuit and
associated regions, which is involved in the neurobiology of major depressive
disorder (MDD). However, few studies are designed to examine the insular
connectivity in MDD. This study was performed to examine the insular connectivity
in drug-naive MDD directly by using the insular cortices as seeds. METHODS:
Functional magnetic resonance imaging data were obtained from 44 drug-naive MDD
patients and 44 healthy controls at rest. The functional connectivity (FC) method
was used to analyze the images. RESULTS: Significantly decreased FCs were found
between the right insula and the left middle frontal gyrus (MFG, orbital part),
left superior temporal gyrus (STG), right putamen, and right middle occipital
gyrus (MOG), and between the left insula and the left superior temporal pole and
right MOG in the patients compared with the controls. There were significantly
negative correlations between the z values of the left insula-left superior
temporal pole connectivity and the current episode duration (r=-0.332, p=0.028),
between the z values of the right insula-left STG connectivity and the episode
number (r=-0.343, p=0.023), and between the z values of the right insula-left MFG
(orbital part) connectivity and the Automatic Thoughts Questionnaire scores (r=
0.359, p=0.017) in the patients. CONCLUSIONS: The findings reveal that depressed
patients have decreased insular connectivity with the fronto-limbic circuit, hate
circuit, and visual regions, and suggest that the insula may act as an
integration center of emotional processing which is disrupted in the depressed
patients.
PMID- 25845748
TI - Symptom-specific course trajectories and their determinants in primary care
patients with Major Depressive Disorder: Evidence for two etiologically distinct
prototypes.
AB - BACKGROUND: The course-heterogeneity of Major Depressive Disorder (MDD) hampers
development of better prognostic models. Although latent class growth analyses
(LCGA) have been used to explain course-heterogeneity, such analyses have failed
to also account for symptom-heterogeneity of depressive symptoms. Therefore, the
aim was to identify more specific data-driven subgroups based on patterns of
course-trajectories on different depressive symptom domains. METHODS: In primary
care MDD patients (n=205), the presence of the MDD criterion symptoms was
determined for each week during a year. Weekly 'mood/cognition' (MC) and
'somatic' (SOM) scores were computed and parallel processes-LCGA (PP-LCGA) was
used to identify subgroups based on the course on these domains. The classes'
associations with baseline predictors and 2-/3-year outcomes were investigated.
RESULTS: PP-LCGA identified four classes: quick recovery, persisting SOM,
persisting MC, and persisting SOM+MC (chronic). Persisting SOM was specifically
predicted by higher baseline somatic symptomatology and somatization, and was
associated with more somatic depressive symptomatology at long-term follow-up.
Persisting MC was specifically predicted by higher depressive severity, thinking
insufficiencies, neuroticism, loneliness and lower self-esteem, and was
associated with lower mental health related quality of life and more
mood/cognitive depressive symptomatology at follow-up. LIMITATIONS: The sample
was small and contained only primary care MDD patients. The weekly depression
assessments were collected retrospectively at 3-month intervals. CONCLUSIONS: The
results indicate that there are two specific prototypes of depression,
characterized by either persisting MC or persisting SOM, which have different
sets of associated prognostic factors and long-term outcomes, and could have
different etiological mechanisms.
PMID- 25845749
TI - Association between HLA-DRB1*0405, -DQB1*0401 and -DQA1*0303 alleles and
lamotrigine-induced cutaneous adverse drug reactions. A pilot case-control study
from Japan.
AB - BACKGROUND: Human leukocyte antigen (HLA) genotypes in lamotrigine -induced (LTG
induced) cutaneous adverse drug reactions (cADRs) have been described in several
reports but controversy remains even for a given ethnic group. We attempted to
clarify a possible association between LTG-induced cADRs and HLA alleles in
Japanese patients. METHOD: Sixteen subjects, including eight patients with LTG
induced cADRs and eight LTG-tolerant controls were included in this study. All
eight patients with LTG-induced cADRs gave positive results in a drug-induced
lymphocyte stimulation test (DLST) with LTG. We performed HLA-typing for HLA-A,
B, -C, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1, using PCR with sequence-specific
oligonucleotide probes and multiple analyte profiling (xMAP) technology (Luminex
System; Luminex Corporation, Austin, TX). We examined differences between allele
frequencies in our two groups of subjects and the allele frequencies in the
general Japanese population. RESULTS: The frequencies of HLA-DRB1*0405, and HLA
DQB1*0401 alleles were higher in our LTG-cADRs patients than the reference
frequencies in the general Japanese population. We also detected HLA-DQA1*0303
frequently in our LTG-cADRs patients, but data for this allele in the Japanese
population was not available. Our observation was presumably due to the linkage
disequilibrium among the three alleles. The haplotype frequency of HLA-DRB1*0405,
DQB1*0401 and DQA1*0303 in our LTG-cADRs subjects was also different from the
corresponding haplotype frequency in the database for the Japanese population and
the difference was statistically significant. One patient with the HLA-DRB1*0405,
-DQB1*0401 and DQA1*0303 haplotype was safely re-treated with LTG after results
of a DLST with LTG ceased to be positive about 4 months after discontinuation of
LTG. LIMITATIONS: Our analysis included only 16 patients. Associations between
LTG-induced cADRs and specific HLA loci will have to be confirmed in larger
studies. CONCLUSIONS: LTG-induced cADRs are associated with HLA-DRB1*0405,
DQB1*0401 and -DQA1*0303.
PMID- 25845750
TI - Systematic review of neurocognition in people with co-occurring alcohol misuse
and depression.
AB - BACKGROUND: Alcohol misuse and depression represent two major social and health
problems globally. These conditions commonly co-occur and both are associated
with significant cognitive impairment. Despite this, few studies have examined
the impact on cognitive functioning of co-occurring alcohol misuse and
depression. This study aims to critically review findings from peer-reviewed
published articles examining neuropsychological test performance among samples of
people with co-occurring alcohol misuse and depression. METHOD: A comprehensive
literature search was conducted, yielding six studies reporting
neuropsychological profiles of people with co-occurring alcohol misuse and
depression. Results comparing cognitive functioning of people with this
comorbidity to those with alcohol misuse alone, depression alone, healthy
controls and published norms were examined as well as those describing the
correlation between depressive symptoms and cognitive functioning in people with
alcohol use disorders. RESULTS: In the majority of instances, the comorbid groups
did not differ significantly from those with depression only or alcohol misuse
only, nor from healthy controls or published norms. In the cases where a
difference in neuropsychological test scores between groups was found, it was not
consistently identified across studies. However, visual memory was identified in
two studies as being impaired in comorbid samples and is worthy of inclusion in
future studies. LIMITATIONS: Due to the small number of included studies and the
large variation in inclusion criteria as well as differing assessment tools and
methodologies between studies, the review did not include a quantitative
synthesis. CONCLUSIONS: Research into cognitive deficits among people with singly
occurring versus co-occurring alcohol misuse and depression is accumulating.
Evidence suggests that the neuropsychological performance among samples with this
comorbidity is generally not severely impaired and is unlikely to preclude
benefit from treatment.
PMID- 25845751
TI - Instruments that prospectively predict bipolar disorder - A systematic review.
AB - BACKGROUND: Identification of earlier stages of Bipolar Disorder (BD), even prior
to the first manic episode, may help develop interventions to prevent or delay
the onset of BD. However, reliable and valid instruments are necessary to
ascertain such earlier stages of BD. The aim of the current review was to
identify instruments that had predictive validity and utility for BD for use in
early intervention (EI) settings for the prevention of BD. METHODS: We undertook
a systematic examination of studies that examined participants without BD I or II
at baseline and prospectively explored the predictive abilities of instruments
for BD onset over a period of 6 months or more. The instruments and the studies
were rated with respect to their relative validity and utility predicting onset
of BD for prevention or early intervention. Odds ratios and area under the curve
(AUC) values were derived when not reported. RESULTS: Six studies were included,
identifying five instruments that examined sub-threshold symptoms, family
history, temperament and behavioral regulation. Though none of the identified
instruments had been examined in high-quality replicated studies for predicting
BD, two instruments, namely the Child Behavioral Checklist - Pediatric BD
phenotype (CBCL-PBD) and the General Behavioral Inventory - Revised (GBI-R), had
greater levels of validity and utility. LIMITATION: Non-inclusion of studies and
instruments that incidentally identified BD on follow-up limited the breadth of
the review. CONCLUSION: Instruments that test domains such as subthreshold
symptoms, behavioral regulation, family history, and temperament hold promise in
predicting BD onset.
PMID- 25845752
TI - Prevalence of major depressive disorder and socio-demographic correlates: Results
of a representative household epidemiological survey in Beijing, China.
AB - BACKGROUND: Major depressive disorder (MDD) is the most prevalent mental disorder
in the general population and has been associated with socioeconomic factors.
Beijing has undergone significant socioeconomic changes in last decade, however
no large-scale community epidemiological surveys of MDD have been conducted in
Beijing since 2003. AIMS: To determine the prevalence of MDD and its socio
demographic correlates in a representative household sample of the general
population in Beijing, China. METHOD: Data were collected from the 2010
representative household epidemiological survey of mental disorders in Beijing.
The multistage cluster random sampling method was used to select qualified
subjects in 18 districts and counties, and then face-to-face interviews were
administered using the Chinese version of Structured Clinical Interview for DSM
IV-TR Axis I Disorders-Patient Edition (SCID-I/P) during November 1, 2010 to
December 31, 2010. RESULTS: 19,874 registered permanent residents were randomly
identified and 16,032 (response rate=80.7%) completed face-to-face interviews.
The time-point and life-time prevalence rates of MDD were estimated to be 1.10%
(95% CI: 0.94-1.26%) and 3.56% (95% CI: 3.27-3.85%) respectively. Significant
differences were found in sex, age, location of residence, marital status,
education, employment status, personal/family monthly income, perception of
family environment and relationship with others, when comparing residents with
MDD to those without MDD. Those who were female, aged 45 or above, reported low
family income, or reported an "average" or "poor" family environment were
associated with a higher risk of MDD. CONCLUSIONS: The prevalence of MDD reported
in this survey is relatively lower than that in other western countries. Female
sex, age older than 45, low family income, and poor family environment appear to
be independent risk factors for MDD.
PMID- 25845753
TI - Evaluation of adjuvant activity of fractions derived from Agaricus blazei, when
in association with the recombinant LiHyp1 protein, to protect against visceral
leishmaniasis.
AB - The development of effective prophylactic strategies to prevent leishmaniasis has
become a high priority. No less important than the choice of an antigen, the
association of an appropriate adjuvant is necessary to achieve a successful
vaccination, as the majority of the tested antigens contain limited immunogenic
properties, and need to be supplemented with immune response adjuvants in order
to boost their immunogenicity. However, few effective adjuvants that can be used
against leishmaniasis exist on the market today; therefore, it is possible to
speculate that the research aiming to identify new adjuvants could be considered
relevant. Recently, Agaricus blazei extracts have proved to be useful in
enhancing the immune response to DNA vaccines against some diseases. This was
based on the Th1 adjuvant activity of the polysaccharide-rich fractions from this
mushroom. In this context, the present study evaluated purified fractions derived
from Agaricus blazei as Th1 adjuvants through in vitro assays of their immune
stimulation of spleen cells derived from naive BALB/c mice. Two of the tested six
fractions (namely F2 and F4) were characterized as polysaccharide-rich fractions,
and were able to induce high levels of IFN-gamma, and low levels of IL-4 and IL
10 in the spleen cells. The efficacy of adjuvant action against L. infantum was
evaluated in BALB/c mice, with these fractions being administered together with a
recombinant antigen, LiHyp1, which was previously evaluated as a vaccine
candidate, associated with saponin, against visceral leishmaniasis (VL). The
associations between LiHyp1/F2 and LiHyp1/F4 were able to induce an in vivo Th1
response, which was primed by high levels of IFN-gamma, IL-12, and GM-CSF, by low
levels of IL-4 and IL-10; as well as by a predominance of IgG2a antibodies in the
vaccinated animals. After infection, the immune profile was maintained, and the
vaccines proved to be effective against L. infantum. The immune stimulatory
effects in the BALB/c mice proved to be similar when comparing the F2 and F4
fractions with a known Th1 adjuvant (saponin), though animals vaccinated with
saponin did present a slight to moderate inflammatory edema on their hind
footpads. In conclusion, the F2 and F4 fractions appear to induce a Th1-type
immune response and, in this context, they could be evaluated in association with
other protective antigens against Leishmania, as well as in other disease models.
PMID- 25845754
TI - Prevalence and molecular characterization of Giardia duodenalis isolates from
dairy cattle in northeast China.
AB - Giardia duodenalis is an important zoonotic intestinal parasite responsible for
diarrhea in humans and other animals worldwide. The present study was conducted
to assess the prevalence of bovine giardiosis and to perform molecular
characterization of Giardia duodenalis in the northeast of China. A total of 655
fecal specimens were collected from dairy cattle in 15 farms located in three
different provinces. G. duodenalis assemblages and subtypes were determined by
sequence analysis of the triosephosphate isomerase (TPI) gene. As a whole, the G.
duodenalis infection rate in dairy cattle was 7.9% (52/655), as determined by
Lugol's iodine staining. Two assemblages were identified, namely, the potentially
zoonotic assemblage A (n = 1), the livestock-specific assemblage E (n = 50), and
a mixed infection case of assemblages A and E. Seven distinct subtypes of E
assemblages were identified and E-XI, E-I and E-III are the major subtypes. Only
subtype A-I was identified in assemblage A. Findings relevant to assemblage A are
of public health importance. The results indicated the livestock-specific
assemblage E is the major genotype and zoonotic assemblage A or B occurs very
seldomly which is significantly different with previous report in the same area.
So that determination of genotypes in individual epidemiological setting can make
important contributions to public health.
PMID- 25845755
TI - Subtype-specific influenza A virus antibodies in Canada geese (Branta
canadensis).
AB - Historically, surveillance for influenza A viruses (IAVs) in wild birds has
relied on viral detection assays. This was largely due to poor performance of
serological assays in wild birds; however, recently developed commercial
serological assays have improved the ability to detect IAV antibodies in wild
birds. Serological surveillance for IAV antibodies in Canada geese (Branta
canadensis) has shown that, despite a low prevalence of virus isolations, Canada
geese are frequently exposed to IAVs and that exposure increases with latitude,
which follows virus isolation prevalence patterns observed in dabbling ducks. The
objectives of this study were to further evaluate IAV antibodies in Canada geese
using a subtype-specific serological assay to determine if Canada geese are
exposed to subtypes that commonly circulate in dabbling ducks. We collected serum
samples from Canada geese in Minnesota, New Jersey, Pennsylvania, and Wisconsin
and tested for antibodies to IAVs using a blocking ELISA. Positive samples were
further tested by hemagglutination inhibition for 10 hemagglutinin IAV subtypes
(H1-H10). Overall, we detected antibodies to NP in 24% (714/2919) of geese.
Antibodies to H3, H4, H5, and H6 subtypes predominated, with H5 being detected
most frequently. A decrease in H5 HI antibody prevalence and titers was observed
from 2009 to 2012. We also detected similar exposure pattern in Canada geese from
New Jersey, Minnesota, Washington and Wisconsin. Based on the published
literature, H3, H4, and H6 viruses are the most commonly reported IAVs from
dabbling ducks. These results indicate that Canada geese also are frequently
exposed to viruses of the same HA subtypes; however, the high prevalence of
antibodies to H5 viruses was not expected as H5 IAVs are generally not well
represented in reported isolates from ducks.
PMID- 25845756
TI - Arabidopsis flower development--of protein complexes, targets, and transport.
AB - Tremendous progress has been achieved over the past 25 years or more of research
on the molecular mechanisms of floral organ identity, patterning, and
development. While collections of floral homeotic mutants of Antirrhinum majus
laid the foundation already at the beginning of the previous century, it was the
genetic analysis of these mutants in A. majus and Arabidopsis thaliana that led
to the development of the ABC model of floral organ identity more than 20 years
ago. This intuitive model kick-started research focused on the genetic mechanisms
regulating flower development, using mainly A. thaliana as a model plant. In
recent years, interactions among floral homeotic proteins have been elucidated,
and their direct and indirect target genes are known to a large extent. Here, we
provide an overview over the advances in understanding the molecular mechanism
orchestrating A. thaliana flower development. We focus on floral homeotic protein
complexes, their target genes, evidence for their transport in floral primordia,
and how these new results advance our view on the processes downstream of floral
organ identity, such as organ boundary formation or floral organ patterning.
PMID- 25845757
TI - Impact of Non-Pulmonary Vein Foci on the Outcome of the Second Session of
Catheter Ablation for Paroxysmal Atrial Fibrillation.
AB - BACKGROUND: Paroxysmal atrial fibrillation (AF) is primarily triggered by
pulmonary veins (PVs). However, non-PV AF foci may also trigger AF. METHODS: We
examined 207 patients (mean age, 62 +/- 11 years; 166 men) who underwent a second
catheter ablation (CA) and evaluated the clinical significance of non-PV AF foci
on the outcomes. RESULTS: Electrical reconnections between the PVs and left
atrium (LA) were observed in 162 patients (78.3%). Non-PV AF foci were identified
in 95 patients (45.9%, 60 patients with successfully ablated non-PV AF foci and
35 with unmappable non-PV AF foci). During a median follow-up period of 22.7
months, 61 patients (29.5%; 18/112 [16.1%] without non-PV AF foci vs. 20/60
[33.3%] with successfully ablated non-PV AF foci vs. 23/35 [65.7%] with
unmappable non-PV AF foci, P < 0.0001) developed AF recurrence; 52 (85.2%)
developed recurrence within 1 year. The presence of non-PV AF foci was a
significant clinical predictor of AF recurrence after the second CA; successfully
ablated non-PV AF foci increased the AF recurrence risk by 2.24 times (95%
confidence interval [CI], 1.12-4.54; P = 0.02), and unmappable AF foci increased
this risk by 5.58 times (95% CI, 2.73-11.63; P < 0.0001). CONCLUSION: Nearly half
of the patients had non-PV AF foci at the second CA session. AF recurred after
the second CA session in approximately 30%, with most recurrences happening
within 1 year. The presence of non-PV AF foci significantly increased the AF
recurrence risk after a second CA. When non-PV AF foci were unmappable, the AF
recurrence rate was extremely high.
PMID- 25845758
TI - Expression of ribosome-binding protein 1 correlates with shorter survival in Her
2 positive breast cancer.
AB - The aim of this study is to investigate the expression of ribosome-binding
protein 1 (RRBP1) in invasive breast cancer and to analyze its relationship to
clinical features and prognosis. RRBP1 expression was studied using real-time
quantitative PCR and western blotting using pair-matched breast samples and
immunohistochemical staining using a tissue microarray. Then the correlation
between RRBP1 expression and clinicopathologic features was analyzed. RRBP1 mRNA
and protein expression were significantly increased in breast cancer tissues
compared with normal tissues. The protein level of RRBP1 is proved to be
positively related to histological grade (P = 0.02), molecular subtype (P =
0.048) and status of Her-2 (P = 0.026) and P53 (P = 0.015). We performed a grade
stratified analysis of all patients according to the level of RRBP1 expression
and found that RRBP1 overexpression highly affected overall survival in patients
with early-stage (I and II) tumors (P = 0.042). Furthermore, Her-2 positive
patients with negative RRBP1 expression had longer overall survival rates than
those with positive RRBP1 expression (P = 0.031). Using multivariate analysis, it
was determined that lymph node metastasis (LNM, P = 0.002) and RRBP1 expression
(P = 0.005) were independent prognosis factors for overall survival. RRBP1 is a
valuable prognostic factor in Her-2-positive breast cancer patients, indicating
that RRBP1 is a potentially important target for the prediction of prognosis.
PMID- 25845759
TI - Safety of intravenous thrombolysis for acute ischemic stroke in specific
conditions.
AB - INTRODUCTION: Intravenous administration of tissue-type plasminogen activator (IV
tPA) remains the only approved therapy that may reverse neurological deficit in
patients with acute ischemic stroke (AIS). During the past 20 years, accumulating
real-word experience have provided additional information regarding its safety
and efficacy in various clinical settings that were originally considered as
contraindications for systemic thrombolysis. AREAS COVERED: In this narrative
review, we address the safety of intravenous thrombolysis (IVT) in specific
conditions: dissection of the aortic arch of extracranial and intracranial
arteries, concomitant presence of unruptured intracranial aneurysms,
arteriovenous malformations and dural fistulas, co-existing brain tumors as well
as in conditions mimicking AIS. The review systematically evaluates the safety of
off-label use of IVT and summarizes data from case reports of uncommon
complications of systemic thrombolysis administration in the setting of acute
cerebral ischemia. EXPERT OPINION: The present narrative review summarizing 20
years of clinical experience with IVT for AIS highlights that many of the current
guidelines and protocols should be adjusted to accommodate recent data from
registries and real-world experience underscoring the safety of IVT in numerous
conditions of AIS that were originally considered as relative or absolute
contraindications for administration of IV-tPA.
PMID- 25845761
TI - Similarities of serum anti-ganglioside antibodies in first and third episodes of
recurrent Guillain-Barre syndrome: case report.
PMID- 25845760
TI - Triptolide ameliorates colonic fibrosis in an experimental rat model.
AB - Triptolide is known to exert anti-inflammatory and immunomodulatory activities;
however, its impact on intestinal fibrosis has not been previously examined.
Based on our previous studies of the suppressive activity of triptolide on human
colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide
in Crohn's disease, it was hypothesized that triptolide may have beneficial
effects on intestinal fibrosis. In the present study, colonic fibrosis was
induced in rats by 6 weekly repeated administration with a low-dose of 2,4,6
trinitrobenzene sulfonic acid (TNBS) and was then treated with triptolide or PBS
daily (control) simultaneously. Extracellular matrix (ECM) deposition in the
colon was examined with image analysis of Masson Trichrome staining. Total
collagen levels in colonic homogenates were measured by a Sircol assay. Collagen
Ialpha1 transcripts and collagen I protein were measured ex vivo in the isolated
colonic subepithelial myofibroblasts by reverse transcription-quantitative
polymerase chain reaction and immunoblot analysis, respectively. The results
indicated that triptolide decreased ECM deposition and collagen production in the
colon, and inhibited collagen Ialpha1 transcripts and collagen I protein
expression in the isolated subepithelial myofibroblasts of the rats with colonic
fibrosis. In conclusion, triptolide ameliorates colonic fibrosis in the
experimental rat model, suggesting triptolide may be a promising compound for
inflammatory bowel disease treatment.
PMID- 25845762
TI - Pitfalls in ataxia with ocular motor apraxia type 1: pseudodominant inheritance
and very late onset.
PMID- 25845763
TI - An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose
resveratrol, without effect on frataxin levels.
AB - Friedreich ataxia (FRDA) is due to a triplet repeat expansion in FXN, resulting
in deficiency of the mitochondrial protein frataxin. Resveratrol is a naturally
occurring polyphenol, identified to increase frataxin expression in cellular and
mouse models of FRDA and has anti-oxidant properties. This open-label, non
randomized trial evaluated the effect of two different doses of resveratrol on
peripheral blood mononuclear cell (PBMC) frataxin levels over a 12-week period in
individuals with FRDA. Secondary outcome measures included PMBC FXN mRNA,
oxidative stress markers, and clinical measures of disease severity. Safety and
tolerability were studied. Twenty-four participants completed the study; 12
received low-dose resveratrol (1 g daily) and 12 high-dose resveratrol (5 g
daily). PBMC frataxin levels did not change in either dosage group [low-dose
group change: 0.08 pg/MUg protein (95% CI -0.05, 0.21, p = 0.21); high-dose group
change: 0.03 pg/MUg protein (95% CI -0.10, 0.15, p = 0.62)]. Improvement in
neurologic function was evident in the high-dose group [change in Friedreich
Ataxia Rating Scale -3.4 points, 95% CI (-6.6, -0.3), p = 0.036], but not the low
dose group. Significant improvements in audiologic and speech measures, and in
the oxidative stress marker plasma F2-isoprostane were demonstrated in the high
dose group only. There were no improvements in cardiac measures or patient
reported outcome measures. No serious adverse events were recorded.
Gastrointestinal side-effects were a common, dose-related adverse event. This
open-label study shows no effect of resveratrol on frataxin levels in FRDA, but
suggests that independent positive clinical and biologic effects of high-dose
resveratrol may exist. Further assessment of efficacy is warranted in a
randomized placebo-controlled trial.
PMID- 25845764
TI - Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis.
AB - It has been suggested that corticomotoneuronal drive to ankle dorsiflexors is
greater than to ankle plantar flexor muscles, despite the finding that plantar
flexors are no less active than TA during walking and standing. The present study
was undertaken to determine whether there was differential involvement of distal
lower limb muscles in amyotrophic lateral sclerosis (ALS), to elucidate
pathophysiological mechanisms of selective muscle involvement. Prospective
studies were undertaken in 52 ALS patients, including clinical assessment,
disease staging (revised ALS functional rating scale), Medical Research Council
sum score, and a scale of upper motor neurone (UMN) dysfunction. Motor unit
number estimates (MUNE) and compound muscle action potentials (CMAP) from ankle
dorsiflexors and plantar flexors were used to provide objective measures. A novel
'split leg index' was calculated as follows: SLI = CMAPDF / CMAPPF. In ALS, there
was significantly greater reduction of MUNE and CMAP amplitude recorded from
plantar flexors when compared to dorsiflexors, suggesting preferential
involvement of plantar flexor muscles, underpinning a 'split leg' appearance. The
SLI correlated with clinical plantar flexor strength (R= -0.56, p < 0.001). In no
patient did the SLI suggest preferential dorsiflexor involvement. In subgroup
analyses, mean SLI was greatest in lower limb-onset ALS. In conclusion, the
present study has established dissociated involvement of muscles acting around
the ankle in ALS. We suggest this reflects underlying differences in cortical,
descending or local spinal modulation of these muscles.
PMID- 25845765
TI - Significance of the hot-cross bun sign on T2*-weighted MRI for the diagnosis of
multiple system atrophy.
AB - Although the sensitive detection of putaminal iron deposition by T2*-weighted
imaging (T2*-WI) is of diagnostic value for multiple system atrophy (MSA), the
diagnostic significance of the pontine hot-cross bun (HCB) sign with increased
ferritin-bound iron in the background remains unknown. We retrospectively
evaluated the cases of 33 patients with cerebellar-form MSA (MSA-C) and 21 with
MSA of the parkinsonian form (MSA-P) who underwent an MRI study with a 1.5-T
system. Visualization of the HCB sign, posterior putaminal hypointensity and
putaminal hyperintense rim on T2*-WI was assessed by two neurologists
independently using an established visual grade, and were compared with those on
T2-weighted imaging (T2-WI). The visual grade of pontine and putaminal signal
changes was separately assessed for probable MSA (advanced stage) and possible
MSA (early stage). T2*-WI demonstrated significantly higher grades of HCB sign
than T2-WI (probable MSA-C, n = 27, p < 0.001; possible MSA-C, n = 6, p < 0.05;
probable MSA-P, n = 13, p < 0.01). The visual grade of the HCB sign on T2*-WI in
the possible MSA-C patients was comparable to that in the probable MSA-C
patients. Although the HCB sign in MSA-P was of lower visual grade than in MSA-C
even on T2*-WI, some patients showed evolution of the HCB sign preceding the
appearance of the putaminal changes. These findings suggest that T2*-WI is of
extreme value for detecting the HCB sign, which is often cited as a hallmark of
MSA. The appearance of the HCB sign on T2*-WI might not only support but also
improve the diagnosis of MSA.
PMID- 25845766
TI - Relationship between pituitary stalk (PS) visibility and the severity of hormone
deficiencies: PS interruption syndrome revisited.
AB - CONTEXT: Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined
pituitary hormone deficiency characterized by a triad shown in pituitary imaging,
yet it has never been evaluated due to the visibility of pituitary stalk (PS) in
imaging findings. OBJECTIVE: The major objective of the study was to
systematically describe the disease including clinical presentations, imaging
findings and to estimate the severity of anterior pituitary hormone deficiency
based on the visibility of the PS. METHODS: This was a retrospective study
including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine
and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS
according to the findings on MRI, while the rest had a thin or intersected PS.
Basic characteristics and hormonal status were compared. RESULTS: Of the 74
patients with PSIS, age at diagnosis was 25 (22-28) years. Absent pubertal
development (97.3%) was the most common presenting symptom, followed by short
stature. Insulin tolerance test (ITT) and gonadotrophin-releasing hormone (GnRH)
stimulation test were used to evaluate the function of anterior pituitary. The
prevalence of isolated deficiency in growth hormone (GH), gonadotrophins,
corticotrophin and thyrotrophin were 100%, 97.2%, 88.2% and 70.3%, respectively.
Although the ratio of each deficiency did not vary between patients with
invisible PS and with visible PS, panhypopituitarism occurred significantly more
frequent in patients with invisible PS. Patients with invisible PS had
significantly lower levels of luteinizing hormone (LH), follicle stimulation
hormone (FSH) and hormones from targeted glands including morning cortisol, 24-h
urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and
testosterone (T) in male than patients with visible PS. Moreover, patients with
invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak
cortisol in ITT while peak GH remained unchanged between two groups. CONCLUSIONS:
The prevalence of multiple anterior pituitary hormone deficiency was high in
adult patients with PSIS. And more importantly, we found the visibility of PS
shown on MRI might be an indication of the severity of PSIS.
PMID- 25845767
TI - Biocompatibility assessment of haemodialysis membrane materials by proteomic
investigations.
AB - The exposure of blood to an artificial surface such as the haemodialysis membrane
results in the nearly instantaneous deposition of a layer of plasma proteins. The
composition of the protein layer profoundly influences all subsequent events, and
to a large extent determines the biocompatibility of the biomaterial. In the
present study, we examine the protein adsorption capacity and coagulation
profiles of the polysulfone-based helixone material in comparison to cellulose
triacetate. A differential profiling investigation using shotgun proteomics data
independent analysis was applied to eluates obtained with each membrane after a
dialysis session, in order to assess the function of desorbed proteins.
Functional classification and network analysis performed using bioinformatics
tools shed light on the involvement of adsorbed proteins into important molecular
processes, such as lipid transport and metabolism, cell growth differentiation
and communication, and the coagulation cascade. The collected evidence was
further validated by targeted mass spectrometry using selected reaction
monitoring on proteotypic transitions of key protein effectors, confirming the
different panels of adsorbed protein on each membrane. The coagulation profile
during haemodialysis of patients under polysulfone-based helixone filter
cartridges was also assessed showing a slightly higher platelet activation
profile after the dialysis session. The overall collected evidence highlights a
modulation of the coagulation biological pathway during haemodialysis, which is
largely influenced by the biomaterial used.
PMID- 25845768
TI - Efficacy and safety of empagliflozin monotherapy for 52 weeks in Japanese
patients with type 2 diabetes: a randomized, double-blind, parallel-group study.
AB - INTRODUCTION: The aim of this randomized, double-blind, parallel-group study was
to investigate the safety and efficacy of empagliflozin monotherapy for 52 weeks
in Japanese patients with type 2 diabetes (T2DM). METHODS: In a 12-week dose
finding period, patients [N = 547; mean baseline glycosylated hemoglobin (HbA1c)
7.92-8.02%] received empagliflozin (5, 10, 25, or 50 mg) or placebo. In a 40-week
extension period, patients on empagliflozin 10 or 25 mg continued the same
treatment and patients on other doses were reallocated to empagliflozin 10 or 25
mg. Outcomes at week 52 included changes from baseline in HbA1c, fasting plasma
glucose (FPG), weight and blood pressure (BP) in patients who received
empagliflozin 10 or 25 mg in both the initial 12 weeks and the extension and
safety in patients treated with >=1 dose of empagliflozin 10 or 25 mg. RESULTS:
Adjusted mean +/- SE changes in HbA1c from baseline at week 52 were -0.67 +/-
0.09% and -0.86 +/- 0.09%, in FPG were -24.7 +/- 3.2 mg/dL and -31.3 +/- 3.4
mg/dL, and in body weight were -3.1 +/- 0.4 kg and -3.1 +/- 0.4 kg, with
empagliflozin 10 and 25 mg, respectively. Both doses reduced systolic and
diastolic BP. Adverse events were reported in 70.8% and 66.8% of patients on
empagliflozin 10 and 25 mg, respectively. Confirmed hypoglycemic adverse events
(plasma glucose <=70 mg/dL and/or requiring assistance) were reported in one
patient per group. CONCLUSION: Empagliflozin monotherapy for 52 weeks led to
sustained reductions in HbA1c, FPG, weight and BP and was well tolerated in
Japanese patients with T2DM. FUNDING: Boehringer Ingelheim and Eli Lilly and
Company.
PMID- 25845769
TI - Asthma control: the right inhaler for the right patient.
AB - Inhaled therapy is the cornerstone of asthma management in that it optimizes the
delivery of the medication to the site of action. The effectiveness of inhaled
therapy is affected by the correct choice of the device and proper inhalation
technique. In fact, this influences the drug delivery and distribution along the
bronchial tree, including the most peripheral airways. In this context,
accumulating evidence supports the contribution of small airways in asthma, and
these have become an important target of treatment. In reality, the "ideal
inhaler" does not exist, and not all inhalers are the same. Advances in
technology has highlighted these differences, and have led to the design of new
devices and the development of formulations characterized by extrafine particles
that facilitate the distribution and deposition of the drug particles along the
respiratory tract. In addition, efforts have been made to implement adherence to
chronic treatment, which translates into clinical benefit. Taken together, the
optimal control of asthma depends on the drug that is selected, the device that
is employed and the removal of factors that reduce patient's adherence to
therapy.
PMID- 25845771
TI - Spray-dried amikacin sulphate powder for inhalation in cystic fibrosis patients:
The role of ethanol in particle formation.
AB - A Central Composite Design (CCD) was applied in order to identify positive
combinations of the production parameters of amikacin sulphate spray-dried
powders for inhalation, with the intent to expand the experimental space defined
in a previous half-fractional factorial design. Three factors, namely drying
temperature, feed rate and ethanol proportion, have been selected out of the
initial five. In addition, the levels of these factors were increased from two to
three and their effect on amikacin respirability was evaluated. In particular,
focus was given on the role of ethanol presence on the formation of the
microparticles for inhalation. The overall outcome of the CCD was that amikacin
respirability was not substantially improved, as the optimum region coincided
with areas already explored with the fractional factorial design. However,
expanding the design space towards smaller ethanol levels, including its complete
absence, revealed the crucial role of this solvent on the morphology of the
produced particles. Peclet number and drug solubility in the spraying solution
helped to understand the formation mechanism of these amikacin sulphate spray
dried particles.
PMID- 25845770
TI - Molecular dynamics simulations of large macromolecular complexes.
AB - Connecting dynamics to structural data from diverse experimental sources,
molecular dynamics simulations permit the exploration of biological phenomena in
unparalleled detail. Advances in simulations are moving the atomic resolution
descriptions of biological systems into the million-to-billion atom regime, in
which numerous cell functions reside. In this opinion, we review the progress,
driven by large-scale molecular dynamics simulations, in the study of viruses,
ribosomes, bioenergetic systems, and other diverse applications. These examples
highlight the utility of molecular dynamics simulations in the critical task of
relating atomic detail to the function of supramolecular complexes, a task that
cannot be achieved by smaller-scale simulations or existing experimental
approaches alone.
PMID- 25845773
TI - Molecular functionalization of silicene/Ag(111) by covalent bonds: a DFT study.
AB - Among the 2D crystals, silicene, which forms sp(2)-sp(3) bonds, is expected to
present a higher reactivity than graphene, characterized by sp(2) bonds only.
However, silicene functionalization, in particular with organic molecules,
remains an open question. By means of density functional theory, we study the
adsorption of benzene, a model organic molecule, on (3 * 3) silicene on the (4 *
4) Ag(111) surface. Our calculations show that the dispersion interactions must
be taken into account in order to describe this system properly. The adsorption
energy is calculated by means of the semi-empirical dispersion-corrected density
functional theory (DFT-D2) and the optB86b-vdW density functional. The charge
density and electron localization function maps indicate that the molecule is
chemisorbed on the silicene surface by means of two Si-C covalent bonds. In
agreement with charge density difference calculations, two C-C double bonds are
formed in the benzene molecule, which adopts a butterfly configuration. The
silicene lattice is slightly deformed upon benzene adsorption, but the Si-Si
distance remains the same as in bare silicene/Ag(111). Bader analysis shows a
charge transfer from top Si atoms to both molecules and Ag substrates. Finally,
we show that the covalent functionalization of silicene is possible.
PMID- 25845772
TI - Synergetic skin targeting effect of hydroxypropyl-beta-cyclodextrin combined with
microemulsion for ketoconazole.
AB - The objective was to develop a ternary skin targeting system for ketoconazole
(KET) using a combined strategy of microemulsion (ME) and cyclodextrin (HP-beta
CD), i.e., KET-CD-ME, which exploits both virtues of cyclodextrin complex and ME
to obtain the synergetic effect. KET-CD-ME was formulated using Labrafil M 1944
CS as oil phase, Solutol HS 15 as surfactant, Transcutol P as cosurfactant, and
HP-beta-CD solution as aqueous phase. The formulation of KET-CD-ME was optimized
and the optimal formulation was characterized in terms of particle size, size
distribution, pH value, and viscosity. Long term stability experiment showed that
HP-beta-CD could increase the physical stability of ternary system and KET
chemical stability. Percutaneous permeation of KET from KET-CD-ME in vitro
through rat skin was investigated in comparison with KET microemulsion (KET-ME),
KET HP-beta-CD inclusion solution (KET-CD), KET aqueous suspension, and
commercial KET cream; the results showed that the combination of ME with HP-beta
CD exhibited significantly synergistic effect on KET deposition within the skin
(29.38 +/- 1.79 MUg/cm(2)) and a slightly synergistic effect on KET penetration
through the skin (11.3 MUg/cm(2)/h). The enhancement of the combination on skin
deposition was further visualized by confocal laser scanning microscope (CLSM).
In vitro sensitivity against Candida parapsilosis test indicated that KET-CD-ME
enhanced KET antifungal activity mainly owing to the solubilization of HP-beta-CD
on KET in the ternary system. Moreover, the interactions between HP-beta-CD and
KET in the ternary system were elucidated through microScale thermophoresis (MST)
and 2D (1)H NMR spectroscopy. The profiles from MST confirmed the host-guest
interactions of HP-beta-CD with KET in the ternary system and a deep insight into
the interactions between KET and HP-beta-CD were obtained by means of 2D (1)H NMR
spectroscopy. The results indicate that the ternary system of ME combination with
HP-beta-CD may be a promising approach for skin targeting delivery of KET.
PMID- 25845774
TI - Dementia: turning fine aspirations into measurable progress.
PMID- 25845775
TI - 1 year on--lessons from the Ebola outbreak for WHO.
PMID- 25845776
TI - Perinatal mental health--towards a robust system of care.
PMID- 25845777
TI - A new social contract for medical innovation.
PMID- 25845778
TI - The outlook for public spending on the National Health Service.
PMID- 25845780
TI - Republicans' bills target science at US environment agency.
PMID- 25845781
TI - Sheena McCormack: helping to prepare the world for PrEP.
PMID- 25845782
TI - Political roots of the struggle for health justice in Latin America.
PMID- 25845783
TI - Wayne Jay Katon.
PMID- 25845784
TI - GBD 2013 and HIV incidence in high income countries.
PMID- 25845785
TI - What are affordable vaccines?
PMID- 25845786
TI - Diagnosis of reversible causes of coma.
PMID- 25845787
TI - Diagnosis of reversible causes of coma.
PMID- 25845788
TI - Diagnosis of reversible causes of coma - Authors' reply.
PMID- 25845789
TI - Diagnosis of reversible causes of coma.
PMID- 25845790
TI - Effects of intensive glycaemic control on ischaemic heart disease - Authors'
reply.
PMID- 25845791
TI - Effects of intensive glycaemic control on ischaemic heart disease.
PMID- 25845792
TI - Alcohol taxation and premature mortality in Europe.
PMID- 25845794
TI - Department of Error.
PMID- 25845793
TI - Cancer and cardiovascular disease: more tightly linked than by chance.
PMID- 25845795
TI - Integrity and the European Society of Cardiology--reply.
PMID- 25845796
TI - A pregnant woman with acute cardiorespiratory failure: dengue myocarditis.
PMID- 25845797
TI - A pulmonary tumor-like mass resolving with antibiotics.
PMID- 25845798
TI - Tubulin inhibitor identification by bioactive conformation alignment
pharmacophore-guided virtual screening.
AB - Microtubules are important cellular component that are critical for proper
cellular function. Microtubules are synthesized by polymerization of alphabeta
tubulin heterodimers called protofilaments. Microtubule dynamics facilitate
proper cell division during mitosis. Disruption of microtubule dynamics by small
molecule agents inhibits mitosis, resulting in apoptotic cell death and
preventing cell cycle progression. To identify a novel small molecule that binds
the alphabeta tubulin interface to affect microtubule dynamics, we developed a
bioactive conformation alignment pharmacophore (BCAP) model to screen tubulin
inhibitors from a huge database. The application of BCAP model generated based on
the known alphabeta-tubulin interface binders enabled us to identify several
small-molecules that cause apoptosis in human promyelocytic leukemia (HL-60)
cells. Virtual screening combined with an in vitro assay yielded 15 cytotoxic
molecules. In particular, ethyl 2-(4-(5-methyl-3-nitro-1H-pyrazol-1
yl)butanamido)-4-phenylthiophene-3-carboxylate (H05) inhibited tubulin
polymerization with an IC50 of 17.6 MUm concentration. The virtual screening
results suggest that the application of an unbiased BCAP pharmacophore greatly
eliminates unlikely compounds from a huge database and maximizes screening
success. From the limited compounds tested in the tubulin polymerization
inhibitor (TPI) assay, compound H05 was discovered as a tubulin inhibitor. This
compound requires further structure activity optimization to identify additional
potent inhibitors from the same class of molecules.
PMID- 25845799
TI - Reliability and sensitivity of a simple isometric posterior lower limb muscle
test in professional football players.
AB - This study aimed (1) to determine the reliability of a simple and quick test to
assess isometric posterior lower limb muscle force in professional football
players and (2) verify its sensitivity to detect reductions in force following a
competitive match. Twenty-nine professional football players performed a 3-s
maximal isometric contraction of the posterior lower limb muscles for both legs
with players lying supine. Both legs were tested using a knee angle of 90 degrees
and 30 degrees measured on a force plate. Players were tested twice with one
week between sessions to verify reliability. Sensitivity was tested following a
full competitive football match. The test showed high reliability for dominant
leg at 90 degrees (CV = 4.3%, ICC = 0.95, ES = 0.15), non-dominant leg at 90
degrees (CV = 5.4%, ICC = 0.95, ES = 0.14), and non-dominant leg at 30 degrees
(CV = 4.8%, ICC = 0.93, ES = 0.30) and good reliability for dominant leg at 30
degrees (CV = 6.3%, ICC = 0.86, ES = 0.05). The measure was sensitive enough to
detect reductions in force for dominant leg at 90 degrees (P = 0.0006, ES > 1),
non-dominant leg at 90 degrees (P = 0.0142, ES = 1), and non-dominant leg at 30
degrees (P = 0.0064, ES > 1) and for dominant leg at 30 degrees (P = 0.0016, ES
> 1). In conclusion, the present test represents a useful and practical field
tool to determine the magnitude of match-induced fatigue of the posterior lower
limb muscles and potentially to track their recovery.
PMID- 25845800
TI - Molecular features of the sortase enzyme family.
AB - Bacteria possess complex and varying cell walls with many surface exposed
proteins. Sortases are responsible for the covalent attachment of specific
proteins to the peptidoglycan of the cell wall of Gram-positive bacteria. Sortase
A of Staphylococcus aureus, which is seen as the archetypal sortase, has been
shown to be essential for pathogenesis and has therefore received much attention
as a potential target for novel therapeutics. Being widely present in Gram
positive bacteria, it is likely that other Gram-positive pathogens also require
sortases for their pathogenesis. Sortases have also been shown to be of
significant use in a range of industrial applications. We review current
knowledge of the sortase family in terms of their structures, functions and
mechanisms and summarize work towards their use as antibacterial targets and
microbiological tools.
PMID- 25845801
TI - Progressive outer retinal necrosis in a renal transplant recipient: a rare
treatment success.
AB - Renal transplant recipients (RTRs) are subject to a variety of opportunistic
infections. We present a rare case of varicella zoster virus-derived progressive
outer retinal necrosis in an RTR, who presented with painless visual blurring.
This clinical entity heralds an extremely poor visual prognosis and is an
important condition to consider in any immunocompromised host. Early diagnosis by
aqueous fluid sampling and immediate institution of combined systemic and
intravitreal antiviral therapy was successful in this individual.
PMID- 25845802
TI - Multiscale Modeling of Gene-Behavior Associations in an Artificial Neural Network
Model of Cognitive Development.
AB - In the multidisciplinary field of developmental cognitive neuroscience,
statistical associations between levels of description play an increasingly
important role. One example of such associations is the observation of
correlations between relatively common gene variants and individual differences
in behavior. It is perhaps surprising that such associations can be detected
despite the remoteness of these levels of description, and the fact that behavior
is the outcome of an extended developmental process involving interaction of the
whole organism with a variable environment. Given that they have been detected,
how do such associations inform cognitive-level theories? To investigate this
question, we employed a multiscale computational model of development, using a
sample domain drawn from the field of language acquisition. The model comprised
an artificial neural network model of past-tense acquisition trained using the
backpropagation learning algorithm, extended to incorporate population modeling
and genetic algorithms. It included five levels of description-four internal:
genetic, network, neurocomputation, behavior; and one external: environment.
Since the mechanistic assumptions of the model were known and its operation was
relatively transparent, we could evaluate whether cross-level associations gave
an accurate picture of causal processes. We established that associations could
be detected between artificial genes and behavioral variation, even under
polygenic assumptions of a many-to-one relationship between genes and
neurocomputational parameters, and when an experience-dependent developmental
process interceded between the action of genes and the emergence of behavior. We
evaluated these associations with respect to their specificity (to different
behaviors, to function vs. structure), to their developmental stability, and to
their replicability, as well as considering issues of missing heritability and
gene-environment interactions. We argue that gene-behavior associations can
inform cognitive theory with respect to effect size, specificity, and timing. The
model demonstrates a means by which researchers can undertake multiscale modeling
with respect to cognition and develop highly specific and complex hypotheses
across multiple levels of description.
PMID- 25845803
TI - Comments on the paper "Medicolegal implications of accuracy of GP referral
letters to specialist breast clinic".
PMID- 25845804
TI - Using Animals in Nursing Research: Bridging Gaps Between Bench, Bedside, and
Practice.
PMID- 25845805
TI - Review and Synthesize Completed Research Through Systematic Review.
AB - The evidence-based health care movement has generated new opportunity for
scholars to generate synthesized sources of evidence. Systematic reviews are
rigorous forms of synthesized evidence that scholars can conduct if they have
requisite skills, time, and access to excellent library resources. Systematic
reviews play an important role in synthesizing what is known and unknown about a
particular health issue. Thus, they have a synergistic relationship with primary
research. They can both inform clinical decisions when the evidence is adequate
and identify gaps in knowledge to inform research priorities. Systematic reviews
can be conducted of quantitative and qualitative evidence to answer many types of
questions. They all share characteristics of rigor that arise from a priori
protocol development, transparency, exhaustive searching, dual independent
reviewers who critically appraise studies using standardized tools, rigor in
synthesis, and peer review at multiple stages in the conduct and reporting of the
systematic review.
PMID- 25845806
TI - Arterial blood pressure but not serum albumin concentration correlates with ADC
ratio values in pediatric posterior reversible encephalopathy syndrome.
AB - INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a clinical
radiological entity affecting both adults and children characterized by
neurotoxicity often in setting of hypertension coupled with distinct brain
magnetic resonance imaging features. Decreased serum albumin level has been
suggested to correlate with the presence of vasogenic brain edema in adult PRES.
Serum albumin has thus been hypothesized to protect against neurotoxicity in PRES
by reducing vasogenic brain edema through its role in maintaining plasma osmotic
pressure and endothelial integrity. The purpose of our study was to investigate
if such correlation between decreased serum albumin level and PRES-related
vasogenic edema could be found in children. METHODS: We conducted a retrospective
study of 25 pediatric patients diagnosed with PRES. Underlying clinical
conditions, presenting symptoms, blood pressures, and serum albumin levels at
onset of symptoms were collected. Brain MR imaging studies were reviewed. We used
a quantitative method to evaluate the degree of vasogenic edema by measuring
apparent diffusion coefficient (ADC) values of the T2-FLAIR hyperintense brain
lesions. RESULTS: No significant correlation was found between serum albumin
level and degree of PRES-related vasogenic edema. A significant correlation was
found between elevated blood pressure and degree of vasogenic edema in the
temporal lobes (p = 0.02 and 0.04, respectively) but not in the other cerebral
lobes or cerebellum. CONCLUSIONS: Our initial results suggest blood pressure, not
serum albumin level, as a main biomarker for brain edema in children with PRES.
Thus, our study does not suggest a protective role of serum albumin against PRES
related neurotoxicity in children.
PMID- 25845807
TI - Conventional 3T brain MRI and diffusion tensor imaging in the diagnostic workup
of early stage parkinsonism.
AB - INTRODUCTION: The aim of this study is to evaluate whether the diagnostic
accuracy of 3 T brain MRI is improved by region of interest (ROI) measures of
diffusion tensor imaging (DTI), to differentiate between neurodegenerative
atypical parkinsonism (AP) and Parkinson's disease (PD) in early stage
parkinsonism. METHODS: We performed a prospective observational cohort study of
60 patients presenting with early stage parkinsonism and initial uncertain
diagnosis. At baseline, patients underwent a 3 T brain MRI including DTI. After
clinical follow-up (mean 28.3 months), diagnoses could be made in 49 patients (30
PD and 19 AP). Conventional brain MRI was evaluated for regions of atrophy and
signal intensity changes. Tract-based spatial statistics and ROI analyses of DTI
were performed to analyze group differences in mean diffusivity (MD) and
fractional anisotropy (FA), and diagnostic thresholds were determined. Diagnostic
accuracy of conventional brain MRI and DTI was assessed with the receiver
operating characteristic (ROC). RESULTS: Significantly higher MD of the centrum
semiovale, body corpus callosum, putamen, external capsule, midbrain, superior
cerebellum, and superior cerebellar peduncles was found in AP. Significantly
increased MD of the putamen was found in multiple system atrophy-parkinsonian
form (MSA-P) and increased MD in the midbrain and superior cerebellar peduncles
in progressive supranuclear palsy (PSP). The diagnostic accuracy of brain MRI to
identify AP as a group was not improved by ROI measures of MD, though the
diagnostic accuracy to identify MSA-P was slightly increased (AUC 0.82 to 0.85).
CONCLUSION: The diagnostic accuracy of brain MRI to identify AP as a group was
not improved by the current analysis approach to DTI, though DTI measures could
be of added value to identify AP subgroups.
PMID- 25845808
TI - Association between idiopathic intracranial hypertension and sigmoid sinus
dehiscence/diverticulum with pulsatile tinnitus: a retrospective imaging study.
AB - INTRODUCTION: The mechanism of occurrence of sigmoid sinus
dehiscence/diverticulum (SSDD) in pulsatile tinnitus (PT) patients remains under
debate. Its association with idiopathic intracranial hypertension (IIH) lacks
evidence, which is important for therapeutic planning and improving the clinical
outcome. This study aimed to evaluate the association between SSDD and IIH by
comparing the prevalence of several established imaging features of IIH between
PT patients with SSDD and healthy volunteers. METHODS: Thirty-three unilateral PT
patients with SSDD identified on CT images and 33 age- and sex-matched healthy
volunteers underwent T1-weighted volumetric magnetic resonance imaging (MRI). The
optic nerve, pituitary gland, transverse sinus, and ventricles were assessed. The
prevalence of established IIH imaging features was compared between the two
groups. Furthermore, the PT patients were divided into two subgroups: PT patients
with dehiscence only and PT patients with diverticulum. The same statistical
analysis was performed on each pathophysiologic entity respectively. RESULTS: The
PT patients with SSDD showed a significantly higher prevalence of empty sella (P
< 0.001), flattened posterior sclera (P = 0.001), vertical tortuosity of the
optic nerve (P = 0.001), protrusion of the optic nerve (P = 0.006), transverse
sinus stenosis (P = 0.011), and distension of the optic nerve sheath (P = 0.000).
There were no significant differences between the PT and control groups in the
maximum widths of the third and fourth ventricles and the lateral ventricle size.
In contrast to controls, the imaging findings persisted in both of
pathophysiologic entities, except for transverse sinus stenosis. CONCLUSIONS:
Several IIH imaging features occur more frequently in PT patients with SSDD than
in healthy individuals, which suggests a potential correlation between SSDD with
PT and IIH.
PMID- 25845809
TI - Human cerebral blood volume measurements using dynamic contrast enhancement in
comparison to dynamic susceptibility contrast MRI.
AB - INTRODUCTION: Cerebral blood volume (CBV) is an important parameter for the
assessment of brain tumors, usually obtained using dynamic susceptibility
contrast (DSC) MRI. However, this method often suffers from low spatial
resolution and high sensitivity to susceptibility artifacts and usually does not
take into account the effect of tissue permeability. The plasma volume (vp) can
also be extracted from dynamic contrast enhancement (DCE) MRI. The aim of this
study was to investigate whether DCE can be used for the measurement of cerebral
blood volume in place of DSC for the assessment of patients with brain tumors.
METHODS: Twenty-eight subjects (17 healthy subjects and 11 patients with
glioblastoma) were scanned using DCE and DSC. vp and CBV values were measured and
compared in different brain components in healthy subjects and in the tumor area
in patients. RESULTS: Significant high correlations were detected between vp and
CBV in healthy subjects in the different brain components; white matter, gray
matter, and arteries, correlating with the known increased tissue vascularity,
and within the tumor area in patients. CONCLUSION: This work proposes the use of
DCE as an alternative method to DSC for the assessment of blood volume, given the
advantages of its higher spatial resolution, its lower sensitivity to
susceptibility artifacts, and its ability to provide additional information
regarding tissue permeability.
PMID- 25845810
TI - Intensity of prolactinoma on T2-weighted magnetic resonance imaging: towards
another gender difference.
AB - INTRODUCTION: Clinical presentations of prolactinomas are quite different between
genders. In comparison with women's prolactinoma, those in men showed
predominance of large tumors with high prolactin (PRL) levels. This preponderance
could be attributed to a greater proliferative potential of the tumors.
Differences in magnetic resonance imaging (MRI) signal at diagnosis have not been
yet clearly evaluated. METHODS: We conduct a retrospective study comparing MRI
signal intensity (SI) on T2-weighted images (T2-WI) between 41 men and 41 women
to investigate whether or not men prolactinoma present specific features.
RESULTS: In addition to the size of the adenoma and PRL levels (P < 0001),
prolactinomas in men also exhibit differences from those in women in signal on T2
WI on MRI (P < 0001). Women's prolactinomas are mostly of high SI on T2-WI while
men's prolactinomas exhibit a more heterogeneous pattern of SI on T2-WI.
Prolactinomas presenting with low SI on T2-WI are almost exclusively encountered
in men. CONCLUSIONS: Presence of T2-WI hypointensities in pituitary adenoma can
be predictive of a different subtype of prolactinoma almost encountered in men
and possibly translate the presence of spherical amyloid deposits, in agreement
with the literature.
PMID- 25845811
TI - Extracranial vertebral artery dissection in children: natural history and
management.
AB - INTRODUCTION: The objective of this study is to describe clinical and imaging
presentation and outcome in extracranial vertebral artery dissection. METHODS:
Single-centre retrospective study over a 14-year period included 20 consecutive
patients under the age of 16 years with extracranial vertebral artery dissection.
The diagnosis was based on vascular imaging performed at the acute phase and
clinical symptoms. RESULTS: A male predominance was observed (sex ratio 9/1). The
first symptoms consisted of headache (45%), neck pain (15%), nausea (30%) and
vertigo (30%). Clinical signs leading to admission to hospital were hemiparesis
(60%), visual disorders with oculomotor disorders (20%) or visual field defects
(20%) and cerebellar syndrome (35%). Eight patients (40%) reported repeated
transient episodes of neurological deficits, prior to the diagnosis. The segment
most commonly affected was V2-V3 (50%), followed by V3 (15%) and V2 (15%), V3-V4
(10%) and proximal V4 (10%). All patients but one presented cerebral infarction.
Eleven patients received first-line treatment with low molecular weight heparin
(LMWH), and nine patients received aspirin. Three patients experienced a
recurrence of symptoms, one under vitamin K antagonist (VKA) and 2 under aspirin.
All three were switched to LMWH with success. Fifty-eight percent of the
dissected arteries were occluded at long-term follow-up, although 73% of them
were patent at the acute phase. CONCLUSION: Initial imaging must include
posterior fossa vessels and the craniocervical region with V2-V3 segments.
Conventional angiography may be indicated in the absence of a definitive
diagnosis on noninvasive imaging. Healing of the dissected vertebral artery
predominantly resulted in occlusion, which does not constitute a pejorative
factor but indicates good quality healing.
PMID- 25845812
TI - Preoperative embolization of intracranial meningiomas using n-butyl
cyanoacrylate.
AB - INTRODUCTION: Preoperative embolization for intracranial meningioma has been
controversial for several decades. This study retrospectively reviewed our
experience using n-butyl cyanoacrylate (n-BCA) to identify the factors for
effective devascularization and procedure-related complications. METHODS: Fifty
seven patients who underwent preoperative embolization with n-BCA were analyzed
to collect the following data: age, sex, tumor size, location, pathology, and
presence or absence of pial arterial supply. The predictive factors for total
devascularization and complications were examined using univariate and
multivariate analyses. RESULTS: Injected n-BCA penetrated into the tumor vessels
in 51 cases (89%) but resulted in feeder occlusion in 6 (11%). Angiographic total
devascularization was achieved in 29 cases (51%) and partial devascularization in
28 (49%). Small size, superficial location, and absence of pial supply were
independent factors for total devascularization. No major complication was
encountered, but asymptomatic or transient adverse events occurred in nine
patients and were significantly associated with elderly patients and large
tumors. CONCLUSION: Preoperative embolization for intracranial meningiomas using
n-BCA can attain effective devascularization without major complications. The
effect of preoperative embolization on surgical resection or patient outcome is
still unknown.
PMID- 25845813
TI - Differentiation of solitary brain metastasis from glioblastoma multiforme: a
predictive multiparametric approach using combined MR diffusion and perfusion.
AB - INTRODUCTION: Solitary brain metastasis (MET) and glioblastoma multiforme (GBM)
can appear similar on conventional MRI. The purpose of this study was to identify
magnetic resonance (MR) perfusion and diffusion-weighted biomarkers that can
differentiate MET from GBM. METHODS: In this retrospective study, patients were
included if they met the following criteria: underwent resection of a solitary
enhancing brain tumor and had preoperative 3.0 T MRI encompassing diffusion
tensor imaging (DTI), dynamic contrast-enhanced (DCE), and dynamic susceptibility
contrast (DSC) perfusion. Using co-registered images, voxel-based fractional
anisotropy (FA), mean diffusivity (MD), K(trans), and relative cerebral blood
volume (rCBV) values were obtained in the enhancing tumor and non-enhancing
peritumoral T2 hyperintense region (NET2). Data were analyzed by logistic
regression and analysis of variance. Receiver operating characteristic (ROC)
analysis was performed to determine the optimal parameter/s and threshold for
predicting of GBM vs. MET. RESULTS: Twenty-three patients (14 M, age 32-78 years
old) met our inclusion criteria. Pathology revealed 13 GBMs and 10 METs. In the
enhancing tumor, rCBV, K(trans), and FA were higher in GBM, whereas MD was lower,
neither without statistical significance. In the NET2, rCBV was significantly
higher (p = 0.05) in GBM, but MD was significantly lower (p < 0.01) in GBM. FA
and K(trans) were higher in GBM, though not reaching significance. The best
discriminative power was obtained in NET2 from a combination of rCBV, FA, and MD,
resulting in an area under the curve (AUC) of 0.98. CONCLUSION: The combination
of MR diffusion and perfusion matrices in NET2 can help differentiate GBM over
solitary MET with diagnostic accuracy of 98%.
PMID- 25845814
TI - Screening and preliminary validation of miRNAs with the regulation of hTERT in
colorectal cancer.
AB - The overexpression of human telomerase reverse transcriptase (hTERT) has been
associated with the invasion and metastasis of colorectal cancer (CRC) and has
received extensive attention, although the underlying mechanism involved remains
unclear. The aim of the present study was to screen and preliminarily validate
new tumor-suppressor microRNAs (miRNAs) that potentially inhibit hTERT expression
and to assess its clinical significance. Screening for downregulated miRNAs in
CRC tissues was performed by retrieving and analysing microRNA microarray data.
miRNA candidates were then filtered by bioinformatics analysis. The expression of
miRNAs candidates was verified by quantitative polymerase chain reaction in the
CRC and corresponding normal tissues. Immunohistochemistry (IHC) was used for the
detection of hTERT protein expression. Spearman's correlation coefficient between
miRNA candidates and hTERT protein expression was calculated (r) to identify
hTERT-targeting miRNAs. A survival analysis was performed to assess the
prognostic significance of hTERT-targeting miRNAs in CRC. Eight miRNAs with the
potential to interact with hTERT were predicted: miR-29c-3p, miR-124-3p, miR-133a
3p, miR-133b, miR-138-5p, miR-150-5p, miR-378a-3p and miR-422a, respectively.
Following detection of the miRNAs using RT-qPCR, miR-29c-3p was excluded. miR-138
5p and miR-422a were observed to potentially interact with hTERT (r=-0.362,
P=0.001; r=-0.306, P=0.005, respectively). The Kaplan-Meier survival curves
demonstrating high- vs. low-expression group of miR-422a showed a highly
significant difference in CRC patients (P=0.024), which suggests that the
downregulation of miR-422a was associated with a poorer prognosis. The results
indicated that miR-138-5p and miR-422a potentially inhibited hTERT expression in
CRC, and suggest a potential application of miR-422a in prognosis prediction and
CRC treatment.
PMID- 25845816
TI - The B32 cluster has the most stable bowl structure with a remarkable heptagonal
hole.
AB - The neutral B32 exhibits an aromatic bowl structure containing one heptagonal
hole, while two anionic species, one having a bowl structure and the other a
quasi-planar structure, are almost degenerate in energy. These findings not only
give more insight into the structural features of boron clusters, but also
present a key result explaining the presence of heptagonal holes in the fullerene
B40.
PMID- 25845815
TI - What is wrong with non-respondents? Alcohol-, drug- and smoking-related mortality
and morbidity in a 12-year follow-up study of respondents and non-respondents in
the Danish Health and Morbidity Survey.
AB - AIM: Response rates in health surveys have diminished over the last two decades,
making it difficult to obtain reliable information on health and health-related
risk factors in different population groups. This study compared cause-specific
mortality and morbidity among survey respondents and different types of non
respondents to estimate alcohol-, drug- and smoking-related mortality and
morbidity among non-respondents. DESIGN: Prospective follow-up study of
respondents and non-respondents in two cross-sectional health surveys. SETTING:
Denmark. PARTICIPANTS: A total sample of 39 540 Danish citizens aged 16 years or
older. MEASUREMENTS: Register-based information on cause-specific mortality and
morbidity at the individual level was obtained for respondents (n = 28 072) and
different types of non-respondents (refusals n = 8954; illness/disabled n = 731,
uncontactable n = 1593). Cox proportional hazards models were used to examine
differences in alcohol-, drug- and smoking-related mortality and morbidity,
respectively, in a 12-year follow-up period. FINDINGS: Overall, non-response was
associated with a significantly increased hazard ratio (HR) of 1.56 [95%
confidence interval (CI) = 1.36-1.78] for alcohol-related morbidity, 1.88 (95% CI
= 1.38-2.57) for alcohol-related mortality, 1.55 (95% CI = 1.27-1.88) for drug
related morbidity, 3.04 (95% CI = 1.57-5.89) for drug-related mortality and 1.15
(95% CI = 1.03-1.29) for smoking-related morbidity. The hazard ratio for smoking
related mortality also tended to be higher among non-respondents compared with
respondents, although no significant association was evident (HR = 1.14; 95% CI =
0.95-1.36). Uncontactable and ill/disabled non-respondents generally had a higher
hazard ratio of alcohol-, drug- and smoking-related mortality and morbidity
compared with refusal non-respondents. CONCLUSION: Health survey non-respondents
in Denmark have an increased hazard ratio of alcohol-, drug- and smoking-related
mortality and morbidity compared with respondents, which may indicate more
unfavourable health behaviours among non-respondents.
PMID- 25845817
TI - Heidegger, ontological death, and the healing professions.
AB - In Being and Time, Martin Heidegger introduces a unique interpretation of death
as a kind of world-collapse or breakdown of meaning that strips away our ability
to understand and make sense of who we are. This is an 'ontological death' in the
sense that we cannot be anything because the intelligible world that we draw on
to fashion our identities and sustain our sense of self has lost all
significance. On this account, death is not only an event that we can
physiologically live through; it can happen numerous times throughout the finite
span of our lives. This paper draws on Arthur Frank's (At the will of the body:
reflections on illness. Houghton, Boston, 1991) narrative of critical illness to
concretize the experience of 'ontological death' and illuminate the unique
challenges it poses for health care professionals. I turn to Heidegger's
conception of 'resoluteness' (Entschlossenheit) to address these challenges,
arguing for the need of health care professionals to help establish a discursive
context whereby the critically ill can begin to meaningfully express and
interpret their experience of self-loss in a way that acknowledges the structural
vulnerability of their own identities and is flexible enough to let go of those
that have lost their significance or viability.
PMID- 25845818
TI - Dual-System Use and Intermediate Health Outcomes among Veterans Enrolled in
Medicare Advantage Plans.
AB - OBJECTIVE: The concurrent use of multiple health care systems may duplicate or
fragment care. We assessed the characteristics of veterans who were dually
enrolled in both the Veterans Affairs (VA) health care system and a Medicare
Advantage (MA) plan, and compared intermediate quality outcomes among those
exclusively receiving care in the VA with those receiving care in both systems.
DATA SOURCES/STUDY SETTING: VA and MA quality and administrative data from 2008
to 2009. STUDY DESIGN: We used propensity score methods to test the association
between dual use and five intermediate outcome quality measures. Outcomes
included control of cholesterol, blood pressure, and glycosylated hemoglobin
among persons with coronary heart disease (CHD), hypertension, and diabetes. DATA
COLLECTION/EXTRACTION METHODS: VA and MA data were merged to identify VA-only
users (n = 1,637) and dual-system users (n = 5,006). PRINCIPAL FINDINGS: We found
no significant differences in intermediate outcomes between VA-only and dual-user
populations. Differences ranged from a 3.2 percentage point (95 percent CI: -1.8
to 8.2) greater rate of controlled cholesterol among VA-only users with CHD to a
2.2 percentage point (95 percent CI: -2.4 to 6.6) greater rate of controlled
blood pressure among dual users with diabetes. CONCLUSIONS: For the five measures
studied, we did not find evidence that veterans with dual use of VA and MA care
experienced improved or worsened outcomes as compared with veterans who
exclusively used VA care.
PMID- 25845819
TI - Guanine-based structural coloration as an indicator of oxidative stress in a
cichlid fish.
AB - Vertebrate pigmentation is known to be influenced by oxidative stress, but few
studies have tested the hypothesis that structural coloration can be similarly
affected. We tested whether fish iridophores, which produce structural color
using guanine stacks, might be affected by the prooxidant-antioxidant balance of
the animal. Specifically, we hypothesized that convict cichlids (Amatitlania
nigrofasciata) metabolize guanine present in iridophores to uric acid, an
antioxidant, in response to oxidative damage. We used Hunter's contrast gloss and
high performance liquid chromatography to determine whether dietary guanine
supplementation allows fish to maintain their structural coloration despite
oxidative stress induced via ultraviolet-B (UV-B) radiation. We found that
dietary guanine was associated with greater skin gloss, and that exposure to UV-B
light reduced glossiness. UV-B exposure did not increase oxidative damage
(acrolein) or total antioxidant capacity in the skin or liver. Our experiment did
not detect effects of dietary guanine or UV-B light on uric acid, but uric acid
was positively related to antioxidant capacity. Our results support the
hypothesis that structural color in fish may be altered by environmental
stressors such as exposure to UV light, and highlight the need for future studies
to consider the role of iridophores in condition-dependent visual signaling.
PMID- 25845820
TI - Adherence to a pedometer-based physical activity intervention following kidney
transplant and impact on metabolic parameters.
AB - The majority of kidney transplant recipients die from cardiovascular events.
Physical activity may be a modifiable risk factor for cardiovascular disease
following transplant. The goal of our study was to examine adherence to a
physical activity intervention following kidney transplant and its impact on
metabolic parameters. All patients who received a kidney transplant at our center
between 12/2010 and 12/2011 received usual care (n = 162), while patients
transplanted between 12/2011 and 1/2013 received a 90-day pedometer-based
physical activity intervention (n = 145). Metabolic parameters were assessed at
four and 12 months post-transplant. Baseline demographics and clinical management
were similar between cohorts. Adherence to the prescription was 36.5%. Patients
in the physical activity cohort had lower systolic and diastolic blood pressure
four months post-transplant compared to the usual care cohort (122 +/- 18 vs. 126
+/- 16 mmHg, p = 0.049 and 73 +/- 10 vs. 77 +/- 9, p = 0.004) and less impaired
fasting glucose (20.7% vs. 30.9%, p = 0.04). Twelve-month outcomes were not
different between cohorts. Over one-third of our cohort adhered to a pedometer
based physical activity intervention following kidney transplant, and the
intervention was associated with improved metabolic parameters. Further study of
post-transplant exercise interventions and methods to optimize long-term
adherence are needed.
PMID- 25845826
TI - Prediction of in vivo clearance and associated variability of CYP2C19 substrates
by genotypes in populations utilizing a pharmacogenetics-based mechanistic model.
AB - It is important to examine the cytochrome P450 2C19 (CYP2C19) genetic
contribution to drug disposition and responses of CYP2C19 substrates during drug
development. Design of such clinical trials requires projection of genotype
dependent in vivo clearance and associated variabilities of the investigational
drug, which is not generally available during early stages of drug development,
but is essential for CYP2C19 substrates with multiple clearance pathways. This
study evaluated the utility of pharmacogenetics-based mechanistic modeling in
predicting such parameters. Hepatic CYP2C19 activity and variability within
genotypes were derived from in vitro S-mephenytoin metabolic activity in
genotyped human liver microsomes (N = 128). These data were then used in
mechanistic models to predict genotype-dependent disposition of CYP2C19
substrates (i.e., S-mephenytoin, citalopram, pantoprazole, and voriconazole) by
incorporating in vivo clearance or pharmacokinetics of wild-type subjects and
parameters of other clearance pathways. Relative to the wild-type, the CYP2C19
abundance (coefficient of variation percentage) in CYP2C19*17/*17, *1/*17, *1/*1,
*17/null, *1/null, and null/null microsomes was estimated as 1.85 (117%), 1.79
(155%), 1.00 (138%), 0.83 (80%), 0.38 (130%), and 0 (0%), respectively. The
subsequent modeling and simulations predicted, within 2-fold of the observed, the
means and variabilities of urinary S/R-mephenytoin ratio (36 of 37 genetic
groups), the oral clearance of citalopram (9 of 9 genetic groups) and
pantoprazole (6 of 6 genetic groups), and voriconazole oral clearance (4 of 4
genetic groups). Thus, relative CYP2C19 genotype-dependent hepatic activity and
variability were quantified in vitro and used in a mechanistic model to predict
pharmacokinetic variability, thus allowing the design of pharmacogenetics and
drug-drug interaction trials for CYP2C19 substrates.
PMID- 25845827
TI - A novel reaction mediated by human aldehyde oxidase: amide hydrolysis of GDC
0834.
AB - GDC-0834, a Bruton's tyrosine kinase inhibitor investigated as a potential
treatment of rheumatoid arthritis, was previously reported to be extensively
metabolized by amide hydrolysis such that no measurable levels of this compound
were detected in human circulation after oral administration. In vitro studies in
human liver cytosol determined that GDC-0834 (R)-N-(3-(6-(4-(1,4-dimethyl-3
oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo- 4,5-dihydropyrazin-2-yl)-2
methylphenyl)-4,5,6,7-tetrahydrobenzo[b] thiophene-2-carboxamide) was rapidly
hydrolyzed with a CLint of 0.511 ml/min per milligram of protein. Aldehyde
oxidase (AO) and carboxylesterase (CES) were putatively identified as the enzymes
responsible after cytosolic fractionation and mass spectrometry-proteomics
analysis of the enzymatically active fractions. Results were confirmed by a
series of kinetic experiments with inhibitors of AO, CES, and xanthine oxidase
(XO), which implicated AO and CES, but not XO, as mediating GDC-0834 amide
hydrolysis. Further supporting the interaction between GDC-0834 and AO, GDC-0834
was shown to be a potent reversible inhibitor of six known AO substrates with
IC50 values ranging from 0.86 to 1.87 MUM. Additionally, in silico modeling
studies suggest that GDC-0834 is capable of binding in the active site of AO with
the amide bond of GDC-0834 near the molybdenum cofactor (MoCo), orientated in
such a way to enable potential nucleophilic attack on the carbonyl of the amide
bond by the hydroxyl of MoCo. Together, the in vitro and in silico results
suggest the involvement of AO in the amide hydrolysis of GDC-0834.
PMID- 25845828
TI - Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis.
AB - Endothelial-to-mesenchymal transition is a phenotypic conversion characterized by
down-regulation of vascular endothelial markers and the acquisition of a
mesenchymal phenotype. We hypothesized that keloid fibroblasts are of endothelial
origin and that endothelial-to-mesenchymal transition substantially contributes
to collagen accumulation during the development and progression of keloids.
Wingless protein (Wnt-3a) protein expression was examined using
immunohistochemistry in keloid tissues. Human dermal microvascular endothelial
cells (HDMECs) were treated with Wnt-3a. mRNA and protein expression of
endothelial (vascular endothelial cadherin) and mesenchymal (vimentin, snail
family transcription factor [slug], and alpha-smooth muscle actin) cell markers
were measured using real-time RT-PCR and immunocytochemistry, respectively.
Additionally, coexpression of CD31 (cluster of differentiation 31), and
endothelial cell marker, and vimentin in the vascular endothelium of keloid
tissues was examined using immunofluorescence. Wnt-3a overexpression was observed
in human keloid tissues. Wnt-3a treatment significantly reduced vascular
endothelial cadherin mRNA expression and induced vimentin and slug mRNA
expression in HDMECs. HDMECs became spindle-shaped and exhibited reduced
expression of CD31 and increased expression of vimentin, slug, and alpha-smooth
muscle actin. Moreover, coexpression of CD31 and vimentin was observed in the
dermal vascular endothelium of keloid tissues from two patients with clinically
active keloids. In conclusion, transient conversion of HDMECs to a mesenchymal
phenotype may contribute to dermal fibrosis of keloid and hypertrophic scars.
PMID- 25845829
TI - Urinary biomarkers for the detection of prostate cancer in patients with high
grade prostatic intraepithelial neoplasia.
AB - INTRODUCTION: High-grade prostatic intraepithelial neoplasia (HGPIN) is a
recognized precursor stage of PCa. Men who present HGPIN in a first prostate
biopsy face years of active surveillance including repeat biopsies. This study
aimed to identify non-invasive prognostic biomarkers that differentiate early on
between indolent HGPIN cases and those that will transform into actual PCa.
METHODS: We measured the expression of 21 candidate mRNA biomarkers using
quantitative PCR in urine sediment samples from a cohort of 90 patients with
initial diagnosis of HGPIN and a posterior follow up of at least two years. Uni-
and multivariate statistical analyses were applied to analyze the candidate
biomarkers and multiplex models using combinations of these biomarkers. RESULTS:
PSMA, PCA3, PSGR, GOLM, KLK3, CDH1, and SPINK1 behaved as predictors for PCa
presence in repeat biopsies. Multiplex models outperformed (AUC = 0.81-0.86) the
predictive power of single genes, including the FDA-approved PCA3 (AUC = 0.70).
With a fixed sensitivity of 95%, the specificity of our multiplex models was of
41-58%, compared to the 30% of PCA3. The PPV of our models (30-38%) was also
higher than the PPV of PCA3 (27%), suggesting that benign cases could be more
accurately identified. Applying statistical models, we estimated that 33% to 47%
of repeat biopsies could be prevented with a multiplex PCR model, representing an
easy applicable and significant advantage over the current gold standard in urine
sediment. DISCUSSION: Using multiplex RTqPCR-based models in urine sediment it is
possible to improve the current diagnostic method of choice (PCA3) to
differentiate between benign HGPIN and PCa cases.
PMID- 25845830
TI - Projections in donor organs available for liver transplantation in the United
States: 2014-2025.
AB - With the aging US population, demographic shifts, and obesity epidemic, there is
potential for further exacerbation of the current liver donor shortage. We aimed
to project the availability of liver grafts in the United States. We performed a
secondary analysis of the Organ Procurement and Transplantation Network database
of all adult donors from 2000 to 2012 and calculated the total number of donors
available and transplanted donor livers stratified by age, race, and body mass
index (BMI) group per year. We used National Health and Nutrition Examination
Survey and Centers for Disease Control and Prevention historical data to stratify
the general population by age, sex, race, and BMI. We then used US population age
and race projections provided by the US Census Bureau and the Weldon Cooper
Center for Public Service and made national and regional projections of available
donors and donor liver utilization from 2014 to 2025. We performed sensitivity
analyses and varied the rate of the rise in obesity, proportion of Hispanics,
population growth, liver utilization rate, and donation after cardiac death (DCD)
utilization. The projected adult population growth in the United States from 2014
to 2025 will be 7.1%. However, we project that there will be a 6.1% increase in
the number of used liver grafts. There is marked regional heterogeneity in liver
donor growth. Projections were significantly affected by changes in BMI, DCD
utilization, and liver utilization rates but not by changes in the Hispanic
proportion of the US population or changes in the overall population growth.
Overall population growth will outpace the growth of available donor organs and
thus potentially exacerbate the existing liver graft shortage. The projected
growth in organs is highly heterogeneous across different United Network for
Organ Sharing regions. Focused strategies to increase the liver donor pool are
warranted.
PMID- 25845831
TI - Cortico-Cortical Connectivity Within Ferret Auditory Cortex.
AB - Despite numerous studies of auditory cortical processing in the ferret (Mustela
putorius), very little is known about the connections between the different
regions of the auditory cortex that have been characterized cytoarchitectonically
and physiologically. We examined the distribution of retrograde and anterograde
labeling after injecting tracers into one or more regions of ferret auditory
cortex. Injections of different tracers at frequency-matched locations in the
core areas, the primary auditory cortex (A1) and anterior auditory field (AAF),
of the same animal revealed the presence of reciprocal connections with
overlapping projections to and from discrete regions within the posterior
pseudosylvian and suprasylvian fields (PPF and PSF), suggesting that these
connections are frequency specific. In contrast, projections from the primary
areas to the anterior dorsal field (ADF) on the anterior ectosylvian gyrus were
scattered and non-overlapping, consistent with the non-tonotopic organization of
this field. The relative strength of the projections originating in each of the
primary fields differed, with A1 predominantly targeting the posterior bank
fields PPF and PSF, which in turn project to the ventral posterior field, whereas
AAF projects more heavily to the ADF, which then projects to the anteroventral
field and the pseudosylvian sulcal cortex. These findings suggest that parallel
anterior and posterior processing networks may exist, although the connections
between different areas often overlap and interactions were present at all
levels.
PMID- 25845832
TI - A week in the life of lung cancer survivors: Daily reports of stress, worry,
mood, and symptoms.
AB - This study examined the day-to-day lives of early stage lung cancer survivors who
were discharged from treatment between 2 and 24 months prior to the study. Lung
cancer survivors were called on eight consecutive nights and completed an
interview about their daily experiences. Repeated measures, multilevel analysis
of the phone interview data was conducted. Survivors reported few daily stressor
exposures or somatic symptoms. Daily moods were generally positive, and survivors
reported living quite independently. Lung cancer survivors did not report
experiencing health-related worry on a daily basis. The findings from this study
create a much more positive picture of lung cancer survivorship relative to prior
studies.
PMID- 25845833
TI - Granting wishes of seriously ill children: Effects on parents' well-being.
AB - We investigated whether a positive intervention (i.e. granting a wish) in
children with a chronic illness could promote positive psychological responses in
their parents. Hospitalized children were randomly assigned to either the wish
group or to a waiting-list control group. Mothers and fathers' responses (N = 86
and 38, respectively) were studied. Parents from the wish group showed higher
levels of positive emotions and beliefs in a benevolent world than the control
group. Mothers from the wish group reported higher benefit finding, gratitude,
and love than those in the control group. Given that the child's illness
inevitably affects their parents, it is important to promote studies that include
parents' well-being dimensions.
PMID- 25845834
TI - Existential challenges experienced by lymphoma survivors: Results from the 2010
LIVESTRONG Survey.
AB - We sought to examine the existential challenges that cancer survivors may
experience as they strive to make meaning, regain their self-identity, cope with
fear of recurrence, and experience feelings of grief and guilt. Lymphoma
survivors (n = 429) completed the 2010 LIVE STRONG: survey and provided responses
about meaning, cancer worry, security, identity, grief, guilt, and perceived
functional impairment due to these concerns. Most survivors (73%-86%) endorsed
existential concerns, with 30-39 percent reporting related perceived functional
impairment. Concerns were associated with being female, younger, unmarried, and
having undergone stem cell transplantation. Lymphoma survivors experience
existential challenges that impact their life even years after diagnosis.
PMID- 25845835
TI - Caregivers' interest in using smokeless tobacco products: Novel methods that may
reduce children's exposure to secondhand smoke.
AB - The study examined caregivers' interest in using potentially reduced exposure
tobacco products for smoking cessation, reduction, and to help them not smoke in
places such as around their child, as all three methods would potentially lead to
reduced secondhand smoke exposure for their children. A sample of 136 caregivers
completed carbon monoxide testing to assess smoking status and a brief survey.
Few caregivers had ever used potentially reduced exposure tobacco products (<1%),
but a majority were interested in trying them as means of smoking reduction
(54%), to quit/stay quit from smoking (51%), and to help them not smoke around
their child or in the home (55%). Caregivers less motivated to quit smoking and
with no home smoking ban were more interested in using potentially reduced
exposure tobacco products to help them quit/stay quit from smoking (p < .05).
PMID- 25845836
TI - Development and validation of the Eating Maturity Questionnaire: Preliminary
findings.
AB - This article describes the development of the Eating Maturity Questionnaire, a
self-reported measurement of eating maturity that initiates and gives direction
to human eating behaviors. The Eating Maturity Questionnaire was designed to
study individuals' biological and psychosocial motives for eating. The Eating
Maturity Questionnaire is a 21-item tool with satisfactory psychometric values
(Cronbach's alpha coefficients between 0.83 and 0.88) consisting of two
subscales: Rational Eating and Psychosocial Maturity Eating Maturity
Questionnaire results may be used to design programs that target eating behaviors
and body mass modification.
PMID- 25845837
TI - Assessment of coagulation utilizing thromboelastometry in dogs undergoing
orthopedic surgery.
AB - OBJECTIVE: To evaluate blood coagulation using thromboelastometry in dogs
following orthopedic surgery. DESIGN: Longitudinal observational study. SETTING:
University veterinary teaching hospital. ANIMALS: Thirty-four adult client-owned
dogs. MEASUREMENTS AND MAIN RESULTS: Dogs undergoing elective or emergency
orthopedic surgery had whole blood collected before (T0), at 24 hours (T1), and 1
week (T2) after surgery. Whole blood from each dog was collected by jugular
venipuncture using a 20-Ga needle and minimum venous stasis. The blood was placed
into tubes containing 3.8% trisodium citrate (1 part citrate: 9 parts blood) and
rested at 37 degrees C. Coagulation was evaluated by means of thromboelastometry
using the in-TEM, ex-TEM, and fib-TEM assays. Statistically significant increases
(P < 0.05) in maximum clot firmness (MCF) from T0 to T1 in the in-TEM and fib-TEM
profiles (both P = 0.0001), from T0 to T2 in the in-TEM, ex-TEM, and fib-TEM
profiles (P = 0.012, P = 0.037, and P = 0.0001, respectively), and from T1 to T2
in the fib-TEM profile (P = 0.039) were noted. The alpha angle increased from T0
to T2 in the in-TEM and ex-TEM profiles (P = 0.019 and P = 0.036, respectively).
All results were, however, within the institutional reference ranges.
CONCLUSIONS: In this study, unlike the hypercoagulability observed in human
orthopedic patients, a hypercoagulable state as measured by thromboelastometry
did not develop in dogs following orthopedic surgery.
PMID- 25845838
TI - The Ruthenostannylene Complex [Cp*(IXy)H2 Ru-Sn-Trip]: Providing Access to
Unusual Ru-Sn Bonded Stanna-imine, Stannene, and Ketenylstannyl Complexes.
AB - Reactivity studies of the thermally stable ruthenostannylene complex
[Cp*(IXy)(H)2 Ru-Sn-Trip] (1; IXy=1,3-bis(2,6-dimethylphenyl)imidazol-2-ylidene;
Cp*=eta(5) -C5 Me5 ; Trip=2,4,6-iPr3 C6 H2 ) with a variety of organic substrates
are described. Complex 1 reacts with benzoin and an alpha,beta-unsaturated ketone
to undergo [1+4] cycloaddition reactions and afford [Cp*(IXy)(H)2 RuSn(kappa(2)
O,O-OCPhCPhO)Trip] (2) and [Cp*(IXy)(H)2 RuSn(kappa(2) -O,C-OCPhCHCHPh)Trip] (3),
respectively. The reaction of 1 with ethyl diazoacetate resulted in a tin
substituted ketene complex [Cp*(IXy)(H)2 RuSn(OC2 H5 )(CHCO)Trip] (4), which is
most likely a decomposition product from the putative ruthenium-substituted
stannene complex. The isolation of a ruthenium-substituted stannene [Cp*(IXy)(H)2
RuSn(=Flu)Trip] (5) and stanna-imine [Cp*(IXy)(H)2 RuSn(kappa(2) -N,O-NSO2 C6 H4
Me)Trip] (6) complexes was achieved by treatment of 1 with 9-diazofluorene and
tosyl azide, respectively.
PMID- 25845839
TI - Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma.
AB - The early detection of hepatocellular carcinoma (HCC) presents a challenge
because of the lack of specific biomarkers. Serum/plasma microRNAs (miRNAs) can
discriminate HCC patients from controls. We aimed to identify and evaluate HCC
associated plasma miRNAs originating from the liver as early biomarkers for
detecting HCC. In this multicenter three-phase study, we first performed
screening using both plasma (HCC before and after liver transplantation or liver
hepatectomy) and tissue samples (HCC, para-carcinoma and cirrhotic tissues).
Then, we evaluated the diagnostic potential of the miRNAs in two case-control
studies (training and validation sets). Finally, we used two prospective cohorts
to test the potential of the identified miRNAs for the early detection of HCC.
During the screening phase, we identified ten miRNAs, eight of which (miR-20a-5p,
miR-25-3p, miR-30a-5p, miR-92a-3p, miR-132-3p, miR-185-5p, miR-320a and miR-324
3p) were significantly overexpressed in the HBV-positive HCC patients compared
with the HBV-positive cancer-free controls in both the training and validation
sets, with a sensitivity of 0.866 and specificity of 0.646. Furthermore, we
assessed the potential for early HCC detection of these eight newly identified
miRNAs and three previously reported miRNAs (miR-192-5p, miR-21-5p and miR-375)
in two prospective cohorts. Our meta-analysis revealed that four miRNAs (miR-20a
5p, miR-320a, miR-324-3p and miR-375) could be used as preclinical biomarkers
(pmeta < 0.05) for HCC. The expression profile of the eight-miRNA panel can be
used to discriminate HCC patients from cancer-free controls, and the four-miRNA
panel (alone or combined with AFP) could be a blood-based early detection
biomarker for HCC screening.
PMID- 25845840
TI - Is Innate Immunity and Inflammasomes Involved in Pathogenesis of Amyotrophic
Lateral Sclerosis (ALS)?
AB - Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's disease is an axonopathy with
adultonset, progressive and irreversible degeneration of upper and lower motor
neurons. Around 90% of ALS is considered as sporadic ALS (sALS) without apparent
genetic cause while in the familial type of ALS (fALS) at least one affected
blood relative needs to be identified. Both sALS and fALS show similar
progression and pathological profile. Biochemical and immunological roles have
been reported for both types of ALS. It has been suggested that mutation in SOD1
gene would be responsible for the oxidative stress and neurotoxicity. Besides,
oxidative stress, protein aggregation, altered cholinergic synapse, neuro
inflammation and production of pro-inflammatory cytokines have also been
reported. Thus, the focus of the present review was on biochemical and
immunological biomarkers and pathogenic mechanism. Regulatory T cells, pro
inflammatory cytokines and activation of pro-inflammatory signaling pathway are
discussed. The activation of NRL inflammasomes in ALS and the involvement of IL
18, IL-1beta and caspases-1 are also suggested. The presence and importance of
HMGB-1 (DAMP) and activation of Tolllike receptors and/or RAGE also are
envisaged. The patents US20140212508, WO2014145776, WO2014145118, US20140255371,
US20140194427, US20140243400, WO2014128254, WO2014076702, WO2014071449,
WO2014043696, WO2014001742, and WO2013082299 are summarized. This review intends
to evaluate the biochemical and immunological responses and the involvement of
inflammasomes in the pathogenesis of ALS. In the present review, we suggest
hypothetical model for ALS pathogenesis and we discuss some patents that suggest
new treatment and/or therapeutic targets. Due to a large number of patents
covering therapy and control of neurodegenerative diseases, our focus was
restricted only to discuss the latest registered patents in 2014.
PMID- 25845841
TI - Myocardial function and effects of biologic therapy in patients with severe
psoriasis: a prospective echocardiographic study.
AB - BACKGROUND: Psoriasis is a chronic inflammatory disease and is associated with
cardiovascular events. Little is known about subclinical myocardial dysfunction
and potential changes in myocardial function during anti-inflammatory treatment
in these patients. We prospectively studied left ventricular function in patients
with severe psoriasis who initiated biologic therapy. METHODS: Between November 1
2013 and May 31 2014 the study subjects underwent physical, laboratory and
comprehensive echocardiographic examination at baseline and after 3 months of
treatment. Pearson correlation coefficients and Student's t-test were applied to
assess changes in diastolic function (defined as the E/e' ratio) and global
longitudinal strain (GLS). RESULTS: Eighteen patients with severe psoriasis
treated with biologic therapy with a mean follow-up of 85.6 +/- 18.2 days were
included. The patients had a baseline psoriasis area and severity index (PASI) of
12.0 +/- 4.1 and normal left ventricular ejection fraction [(LVEF) 56.3 +/-
3.8%], diastolic dysfunction (E/e' 8.1 +/- 2.1) and GLS (-16.8 +/- 2.1%). At
follow-up, an improvement (baseline vs. follow-up) of PASI (12.0 +/- 4.1 vs. 2.7
+/- 3.1, P < 0.001), E/e' (8.1 +/- 2.1 vs. 6.7 +/- 1.9, P <= 0.001) and GLS (
16.8 +/- 2.1 vs. -18.3 +/- 2.3%, P < 0.001) were recorded. No changes were
demonstrated in LVEF (56.3 +/- 3.8 vs. 56.8 +/- 3.3%, P = 0.31), body mass index
(30.9 +/- 5.7 vs. 31.0 +/- 5.8 kg/m(2) , P = 0.90), mean arterial blood pressure
(103.1 +/- 8.5 vs. 103.7 +/- 10.8 mmHg, P = 0.74). Likewise, no changes were seen
in total cholesterol, low density lipoprotein cholesterol, high density
lipoprotein cholesterol, estimated glomerular filtration rate and glycosylated
haemoglobin. CONCLUSION: In patients with severe psoriasis treatment with
biologic therapy was associated with improved PASI and amelioration of myocardial
dysfunction.
PMID- 25845842
TI - Biosynthesis of the Common Polysaccharide Antigen of Pseudomonas aeruginosa PAO1:
Characterization and Role of GDP-D-Rhamnose:GlcNAc/GalNAc-Diphosphate-Lipid
alpha1,3-D-Rhamnosyltransferase WbpZ.
AB - The opportunistic pathogen Pseudomonas aeruginosa produces two major cell surface
lipopolysaccharides, characterized by distinct O antigens, called common
polysaccharide antigen (CPA) and O-specific antigen (OSA). CPA contains a polymer
of D-rhamnose (D-Rha) in alpha1-2 and alpha1-3 linkages. Three putative
glycosyltransferase genes, wbpX, wbpY, and wbpZ, are part of the CPA biosynthesis
cluster. To characterize the enzymatic function of the wbpZ gene product, we
chemically synthesized the donor substrate GDP-D-Rha and enzymatically
synthesized GDP-D-[(3)H]Rha. Using nuclear magnetic resonance (NMR) spectroscopy,
we showed that WbpZ transferred one D-Rha residue from GDP-D-Rha in alpha1-3
linkage to both GlcNAc- and GalNAc-diphosphate-lipid acceptor substrates. WbpZ is
also capable of transferring D-mannose (D-Man) to these acceptors. Therefore,
WbpZ has a relaxed specificity with respect to both acceptor and donor
substrates. The diphosphate group of the acceptor, however, is required for
activity. WbpZ does not require divalent metal ion for activity and exhibits an
unusually high pH optimum of 9. WbpZ from PAO1 is therefore a GDP-D
Rha:GlcNAc/GalNAc-diphosphate-lipid alpha1,3-D-rhamnosyltransferase that has
significant activity of GDP-D-Man:GlcNAc/GalNAc-diphosphate-lipid alpha1,3-D
mannosyltransferase. We used site-directed mutagenesis to replace the Asp
residues of the two DXD motifs with Ala. Neither of the mutant constructs of wbpZ
(D172A or D254A) could be used to rescue CPA biosynthesis in the DeltawbpZ
knockout mutant in a complementation assay. This suggested that D172 and D254 are
essential for WbpZ function. This work is the first detailed characterization
study of a D-Rha-transferase and a critical step in the development of CPA
synthesis inhibitors. IMPORTANCE: This is the first characterization of a D
rhamnosyltransferase and shows that it is essential in Pseudomonas aeruginosa for
the synthesis of the common polysaccharide antigen.
PMID- 25845843
TI - Secretion of Flagellar Proteins by the Pseudomonas aeruginosa Type III Secretion
Injectisome System.
AB - The opportunistic pathogen Pseudomonas aeruginosa utilizes an injectisome-type
III secretion system (injectisome-T3SS) to elicit cytotoxicity toward epithelial
cells and macrophages. Macrophage killing results from the cytotoxic properties
of the translocated effector proteins (ExoS, ExoT, ExoU, and ExoY) and
inflammasome-mediated induction of pyroptosis. Inflammasome activation can occur
following Nlrc4-mediated recognition of cytosolic translocated flagellin (FliC).
In the present study, we demonstrate that FliC is a secretion substrate of both
the injectisome- and flagellum-associated T3SSs. Molecular analyses indicate that
the first 20 amino-terminal residues of FliC are sufficient for secretion by the
injectisome-T3SS and that the first 100 residues are sufficient for translocation
of FliC into host cells. Although maximal inflammasome activation requires FliC,
activation can also occur in the absence of FliC. This prompted us to examine
whether other flagellar components might also be translocated into cells to
elicit inflammasome activation. Indeed, we find that the flagellar cap (FliD),
hook-associated (FlgK and FlgL), hook (FlgE), and rod (FlgE) proteins are
secretion substrates of the injectisome-T3SS. None of these proteins, however,
result in increased inflammasome activation when they are overexpressed in a fliC
mutant and appear to be translocated into host cells. While a role in
inflammasome activation has been excluded, these data raise the possibility that
flagellar components, which are highly conserved between different bacterial
species, trigger other specific host responses from the extracellular milieu or
contribute to the pathogenesis of P. aeruginosa. IMPORTANCE: The inflammasome is
a host defense mechanism that recognizes invading bacteria and triggers an
inflammatory immune response. The opportunistic pathogen P. aeruginosa produces
both inflammasome agonists and antagonists. In this study, we demonstrate that
overexpression of an agonist suppresses the activity of an antagonist, thereby
resulting in inflammasome activation. Since the relative expression levels of
agonists and antagonists likely vary between strains, these differences could be
important predictors of whether a particular P. aeruginosa strain elicits
inflammasome activation.
PMID- 25845844
TI - CysB Negatively Affects the Transcription of pqsR and Pseudomonas Quinolone
Signal Production in Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa is a Gram-negative bacterium that is ubiquitous in the
environment, and it is an opportunistic pathogen that can infect a variety of
hosts, including humans. During the process of infection, P. aeruginosa
coordinates the expression of numerous virulence factors through the production
of multiple cell-to-cell signaling molecules. The production of these signaling
molecules is linked through a regulatory network, with the signal N-(3
oxododecanoyl) homoserine lactone and its receptor LasR controlling the induction
of a second acyl-homoserine lactone signal and the Pseudomonas quinolone signal
(PQS). LasR-mediated control of PQS occurs partly by activating the transcription
of pqsR, a gene that encodes the PQS receptor and is necessary for PQS
production. We show that LasR interacts with a single binding site in the pqsR
promoter region and that it does not influence the transcription of the
divergently transcribed gene, nadA. Using DNA affinity chromatography, we
identified additional proteins that interact with the pqsR-nadA intergenic
region. These include the H-NS family members MvaT and MvaU, and CysB, a
transcriptional regulator that controls sulfur uptake and cysteine biosynthesis.
We show that CysB interacts with the pqsR promoter and that CysB represses pqsR
transcription and PQS production. Additionally, we provide evidence that CysB can
interfere with the activation of pqsR transcription by LasR. However, as seen
with other CysB-regulated genes, pqsR expression was not differentially regulated
in response to cysteine levels. These findings demonstrate a novel role for CysB
in influencing cell-to-cell signal production by P. aeruginosa. IMPORTANCE: The
production of PQS and other 4-hydroxy-2-alkylquinolone (HAQs) compounds is a key
component of the P. aeruginosa cell-to-cell signaling network, impacts multiple
physiological functions, and is required for virulence. PqsR directly regulates
the genes necessary for HAQ production, but little is known about the regulation
of pqsR. We identified CysB as a novel regulator of pqsR and PQS production, but,
unlike other CysB-controlled genes, it does not appear to regulate pqsR in
response to cysteine. This implies that CysB functions as both a cysteine
responsive and cysteine-unresponsive regulator in P. aeruginosa.
PMID- 25845845
TI - Resources for Genetic and Genomic Analysis of Emerging Pathogen Acinetobacter
baumannii.
AB - Acinetobacter baumannii is a Gram-negative bacterial pathogen notorious for
causing serious nosocomial infections that resist antibiotic therapy. Research to
identify factors responsible for the pathogen's success has been limited by the
resources available for genome-scale experimental studies. This report describes
the development of several such resources for A. baumannii strain AB5075, a
recently characterized wound isolate that is multidrug resistant and displays
robust virulence in animal models. We report the completion and annotation of the
genome sequence, the construction of a comprehensive ordered transposon mutant
library, the extension of high-coverage transposon mutant pool sequencing (Tn
seq) to the strain, and the identification of the genes essential for growth on
nutrient-rich agar. These resources should facilitate large-scale genetic
analysis of virulence, resistance, and other clinically relevant traits that make
A. baumannii a formidable public health threat. IMPORTANCE: Acinetobacter
baumannii is one of six bacterial pathogens primarily responsible for antibiotic
resistant infections that have become the scourge of health care facilities
worldwide. Eliminating such infections requires a deeper understanding of the
factors that enable the pathogen to persist in hospital environments, establish
infections, and resist antibiotics. We present a set of resources that should
accelerate genome-scale genetic characterization of these traits for a reference
isolate of A. baumannii that is highly virulent and representative of current
outbreak strains.
PMID- 25845846
TI - Methenyl-Dephosphotetrahydromethanopterin Is a Regulatory Signal for Acclimation
to Changes in Substrate Availability in Methylobacterium extorquens AM1.
AB - During an environmental perturbation, the survival of a cell and its response to
the perturbation depend on both the robustness and functionality of the metabolic
network. The regulatory mechanisms that allow the facultative methylotrophic
bacterium Methylobacterium extorquens AM1 to effect the metabolic transition from
succinate to methanol growth are not well understood. Methenyl
dephosphotetrahydromethanopterin (methenyl-dH4MPT), an early intermediate during
methanol metabolism, transiently accumulated 7- to 11-fold after addition of
methanol to a succinate-limited culture. This accumulation partially inhibited
the activity of the methylene-H4MPT dehydrogenase, MtdA, restricting carbon flux
to the assimilation cycles. A strain overexpressing the gene (mch) encoding the
enzyme that consumes methenyl-dH4MPT did not accumulate methenyl-dH4MPT and had a
growth rate that was 2.7-fold lower than that of the wild type. This growth
defect demonstrates the physiological relevance of this enzymatic regulatory
mechanism during the acclimation period. Changes in metabolites and enzymatic
activities were analyzed in the strain overexpressing mch. Under these
conditions, the activity of the enzyme coupling formaldehyde with dH4MPT (Fae)
remained constant, with concomitant formaldehyde accumulation. Release of
methenyl-dH4MPT regulation did not affect the induction of the serine cycle
enzyme activities immediately after methanol addition, but after 1 h, the
activity of these enzymes decreased, likely due to the toxicity of formaldehyde
accumulation. Our results support the hypothesis that in a changing environment,
the transient accumulation of methenyl-dH4MPT and inhibition of MtdA activity are
strategies that permit flexibility and acclimation of the metabolic network while
preventing the accumulation of the toxic compound formaldehyde. IMPORTANCE: The
identification and characterization of regulatory mechanisms for methylotrophy
are in the early stages. We report a nontranscriptional regulatory mechanism that
was found to operate as an immediate response for acclimation during changes in
substrate availability. Methenyl-dH4MPT, an early intermediate during methanol
oxidation, reversibly inhibits the methylene-H4MPT dehydrogenase, MtdA, when
Methylobacterium extorquens is challenged to switch from succinate to methanol
growth. Bypassing this regulatory mechanism causes formaldehyde to accumulate.
Fae, the enzyme catalyzing the conversion of formaldehyde to methylene-dH4MPT,
was also identified as another potential regulatory target using this strategy.
The results herein further our understanding of the complex regulatory network in
methylotrophy and will allow us to improve metabolic engineering strategies of
methylotrophs for the production of value-added products.
PMID- 25845849
TI - Male-male affiliation and cooperation characterize the social behavior of the
large-bodied pitheciids, Chiropotes and Cacajao: A review.
AB - Cooperation and affiliation between males may be key to the evolution of large
multimale-multifemale primate groups in some species. Cacajao and Chiropotes form
multimale-multifemale groups larger than those of most other platyrrhines
(Cacajao: over 150 and Chiropotes: up to 80 individuals), and groups exhibit a
high degree of fission-fusion dynamics. In both genera, males engage in
affiliative, sex-specific behaviors and form all-male parties. Males in both
genera also have conspicuous genitalia but can demonstrate sexual crypsis, or
mimicry, wherein testes are retracted, resembling labia. Observed egalitarian
interactions among males suggest that there is scramble competition for access to
females, and aggression between males is uncommon relative to other social
primates. As of yet, there are no genetic data to clarify dispersal patterns, and
while relatedness among males would in part explain their affiliative
relationships, there is some limited evidence for dispersal by males in Cacajao.
In this review of recent studies of male-male social interactions in Chiropotes
and Cacajao, we posit that the ability to maintain large groups in these genera
may be related to the affiliative and perhaps coalitionary relationships between
males, who may or may not be related. Affiliative male-male relationships may
allow for monopolization of groups of females and facilitate group cohesion by
reducing intragroup aggression; however data on male-male interactions with
identified individuals will be required to determine patterns of affiliation,
while genetic studies may be the most practical way of determining dispersal
patterns for these genera.
PMID- 25845847
TI - Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO)
Mediates Export of L-Lysine.
AB - In Escherichia coli, argO encodes an exporter for L-arginine (Arg) and its toxic
analogue canavanine (CAN), and its transcriptional activation and repression, by
Arg and L-lysine (Lys), respectively, are mediated by the regulator ArgP.
Accordingly argO and argP mutants are CAN supersensitive (CAN(ss)). We report the
identification of ybjE as a gene encoding a predicted inner membrane protein that
mediates export of Lys, and our results confirm the previous identification with
a different approach of YbjE as a Lys exporter, reported by Ueda and coworkers
(T. Ueda, Y. Nakai, Y. Gunji, R. Takikawa, and Y. Joe, U.S. patents 7,629,142 B2
[December 2009] and 8,383,363 B1 [February 2013] and European patent 1,664,318 B1
[September 2009]). ybjE was isolated as a multicopy suppressor of the CAN(ss)
phenotype of a strain lacking ArgO. The absence of YbjE did not confer a CAN(ss)
phenotype but instead conferred hypersensitivity to the lysine antimetabolite
thialysine and led to growth inhibition by the dipeptide lysylalanine, which is
associated with elevated cellular Lys content. YbjE overproduction resulted in
Lys excretion and syntrophic cross-feeding of a Lys auxotroph. Constitutive
overexpression of argO promoted Lys cross-feeding that is indicative of a latent
Lys export potential of ArgO. Arg modestly repressed ybjE transcription in an
ArgR-dependent manner, and ArgR displayed Arg-sensitive binding to the ybjE
promoter region in vitro. Our studies suggest that the reciprocal repression of
argO and ybjE, respectively, by Lys and Arg confers the specificity for basic
amino acid export by distinct paths and that such cross-repression contributes to
maintenance of cytoplasmic Arg/Lys balance. We propose that YbjE be redesignated
LysO. IMPORTANCE: This work ascribes a lysine export function to the product of
the ybjE gene of Escherichia coli, leading to a physiological scenario wherein
two proteins, ArgO and YbjE, perform the task of separately exporting arginine
and lysine, respectively, which is distinct from that seen for Corynebacterium
glutamicum, where the ortholog of ArgO, LysE, mediates export of both arginine
and lysine. Repression of argO transcription by lysine is thought to effect this
separation. Accordingly, ArgO mediates lysine export when repression of its
transcription by lysine is bypassed. Repression of ybjE transcription by arginine
via the ArgR repressor, together with the lysine repression of argO effected by
ArgP, is indicative of a mechanism of maintenance of arginine/lysine balance in
E. coli.
PMID- 25845848
TI - Asthma and allergy in children with and without prior measles, mumps, and rubella
vaccination.
AB - BACKGROUND: The existing literature on the association between measles
vaccination and subsequent risk of allergic disease is inconclusive. The aim of
this study was, therefore, to determine whether measles, mumps, and rubella (MMR)
vaccination administered in early childhood was associated with asthma and
allergic diseases at ages 5, 7 and 13 yrs in a birth cohort. METHODS: In the
Faroe Islands, 640 children were followed from birth. Follow-up examinations at
ages 5, 7 and 13 yrs included a physical examination and a maternal questionnaire
about the child's health. At age 7, total and grass-specific IgE was quantified
in the child's serum, and at age 13, the children underwent skin prick tests
(SPT). The child's vaccination card was reviewed at examinations. RESULTS: At age
5, 533 of 555 children had been vaccinated for MMR. After confounder adjustment,
we found early life MMR vaccination to be associated with a two-third reduction
in the odds of asthma (OR: 0.33, 95% CI: 0.12; 0.90) and hypersensitivity/allergy
(OR: 0.32, 95% CI: 0.11; 0.88) at age 5, and the substantially decreased odds of
asthma were replicated at age 13 (OR: 0.22, 95% CI: 0.08; 0.56). At age 7, serum
total IgE was reduced by 62.8% (CI 95%: -84.3%; -11.9%) in the vaccinated
children. MMR vaccination was not significantly associated with allergic
rhinoconjuctivitis symptoms, eczema, or SPT reactions at age 13. CONCLUSIONS: MMR
vaccination early in life may have a protective effect against allergy at least
up to age 7 and against asthma through age 13 yrs.
PMID- 25845850
TI - High-mobility-group A2 overexpression provokes a poor prognosis of gastric cancer
through the epithelial-mesenchymal transition.
AB - Tumor metastases are the ultimate target in cancer therapy. In epithelial
malignancies, the expression of high-mobility-group A2 (HMGA2) is associated with
disease progression and the epithelial-mesenchymal transition (EMT), which is
involved in the metastatic process. The present study assessed the clinical and
molecular effects of HMGA2 with the malignant tissues of 170 patients with
gastric cancer and gastric cancer cells expressing HMGA2. HMGA2 expression was
determined using immunohistochemistry and analyzed with respect to the
clinicopathological data of patients with this tumor. In the gastric cancer cell
line MKN28, in which HMGA2 was knocked down by two different short-hairpin RNAs,
Transwell migration and invasion assays were conducted and western blotting was
used to detect the altered expression of EMT markers. In patients with gastric
cancer, HMGA2 overexpression correlated with tumor progression and was indicative
of a significantly worse overall survival. Migration and invasion assays using
HMGA2-knocked down MKN28 cells showed a reduction in cell migration and invasion.
The upregulation of E-cadherin, an epithelial marker, and the downregulation of N
cadherin, a mesenchymal marker were observed in HMGA2-knocked down cells. In
addition, expression of the transcriptional factors Snail and Zeb1 and of the EMT
pathway molecule beta-catenin were decreased. HMGA2 overexpression, through its
relationship to EMT, thus seems to aggravate invasion and metastasis in gastric
cancer. It may therefore serve as a predictive marker in determining the clinical
outcome of patients with gastric cancer and offer a promising therapeutic target.
PMID- 25845852
TI - Mode of delivery and childhood hospitalizations for asthma and other wheezing
disorders.
AB - BACKGROUND: Observationally, delivery by Caesarean section is associated with
higher risk of childhood asthma and wheeze in developed Western settings, but
associations are less consistent in other settings. OBJECTIVE: To examine the
association of mode of delivery with hospitalizations for asthma and other
wheezing disorders in a developed non-Western setting with high rates of
Caesarean section. METHODS: Using Cox regression, we examined the adjusted
association of mode of delivery with public hospital admissions for asthma,
bronchitis, and bronchiolitis (International Classification of Diseases, Ninth
Version Clinical Modification 466, 490 and 493) from 9 days to 12 years of age in
a population-representative prospective birth cohort of 8327 Chinese children in
Hong Kong. Confounders included sex, birth and parental characteristics, and
socio-economic position (SEP). RESULTS: Delivery by Caesarean section accounted
for 27% of all births and was not clearly associated with hospitalizations for
asthma and other wheezing disorders to 12 years [hazard ratio (HR) 1.11, 95%
confidence interval (CI) 0.91 to 1.36] compared to vaginal delivery. Similarly,
there were no clear associations to 2 years (HR 1.07, 95% CI 0.83 to 1.38) or 6
years (HR 1.12, 95% CI 0.91 to 1.37), although we cannot rule out residual
confounding by SEP. CONCLUSIONS AND CLINICAL RELEVANCE: We cannot rule out an
association, but our findings suggest that the observed associations of delivery
by Caesarean section with childhood wheezing disorders may vary with setting and
may not be biologically mediated. Further studies with different designs are
needed to clarify the role of the microbiome and mode of delivery in the
aetiology of asthma and other childhood wheezing disorders.
PMID- 25845851
TI - Quantification of cell size using temporal diffusion spectroscopy.
AB - PURPOSE: A new approach has been developed to quantify cell sizes and
intracellular volume fractions using temporal diffusion spectroscopy with
diffusion-weighted acquisitions. METHODS: Temporal diffusion spectra may be used
to characterize tissue microstructure by measuring the effects of restrictions
over a range of diffusion times. Oscillating gradients have been used previously
to probe variations on cellular and subcellular scales, but their ability to
accurately measure cell sizes larger than 10 MUm is limited. By combining
measurements made using oscillating gradient spin echo (OGSE) and a conventional
pulsed gradient spin echo (PGSE) acquisition with a single, relatively long
diffusion time, we can accurately quantify cell sizes and intracellular volume
fractions. RESULTS: Based on a two compartment model (incorporating intra- and
extracellular spaces), accurate estimates of cell sizes and intracellular volume
fractions were obtained in vitro for (i) different cell types with sizes ranging
from 10 to 20 MUm, (ii) different cell densities, and (iii) before and after
anticancer treatment. CONCLUSION: Hybrid OGSE-PGSE acquisitions sample a larger
region of temporal diffusion spectra and can accurately quantify cell sizes over
a wide range. Moreover, the maximum gradient strength used was lower than 15
G/cm, suggesting that this approach is translatable to practical MR imaging.
PMID- 25845853
TI - Endoscopic surgical treatment of maxillary odontogenic cysts.
PMID- 25845854
TI - An electrodiagnostic technique for assessing palmar proper digital nerves of the
hand: Normative data and clinical application.
AB - INTRODUCTION: There is no standard electrodiagnostic technique for palmar proper
digital nerves (PaPDNs). In this study we investigated sensory nerve action
potentials (SNAPs) to PaPDN stimulation in normal subjects and patients. METHODS:
SNAPs of PaPDNs were recorded in response to selective antidromic stimulation at
the web space and mixed nerve stimulation at the wrist in 14 controls. The
selectivity of PaPDN stimulation and the effect of recording electrode position
on SNAP amplitude were studied. The technique was tested in 2 patients with PaPDN
lesions. RESULTS: The technique yielded selective PaPDN stimulation at the web
space. SNAP amplitude to PaPDN stimulation was influenced by age and was larger
than SNAP amplitude to wrist stimulation. The recording electrode positions
influenced SNAP amplitude. In patients, we documented PaPDN lesions, which were
confirmed at surgery, whereas conventional wrist mixed nerve stimulation yielded
negative findings. CONCLUSIONS: Selective PaPDN stimulation at the web space is
feasible and may be helpful for electrodiagnosis of PaPDN lesions.
PMID- 25845855
TI - The role of fat and alcohol in acute pancreatitis: A dangerous liaison.
AB - Excessive alcohol consumption is a major trigger for severe acute pancreatitis
which may lead to multi-organ dysfunction and premature death of the individual.
Hyperlipidaemia is a risk factor for both acute and chronic pancreatitis and the
role of fatty acids in mediating damage has received increasing attention in
recent years. In the pancreas ethanol is metabolised by both oxidative and non
oxidative pathways. The latter, predominant route generates fatty acid ethyl
esters (FAEEs) from fatty acid substrates via the action of diverse enzymes
called FAEE synthases, including carboxylester lipase an enzyme synthesized and
secreted by the acinar cells. Inhibition of the oxidative pathway promotes
formation of FAEEs which induce sustained elevations of cytosolic calcium leading
to inhibition of mitochondrial function, loss of ATP and necrosis of isolated
pancreatic acinar cells. Furthermore, FAEEs undergo hydrolysis in the
mitochondria releasing free fatty acids that exert toxic effects. Our recent work
has shown that pharmacological inhibition of carboxylester lipase ameliorated
detrimental effects of non-oxidative ethanol metabolism in isolated pancreatic
acinar cells in vitro and in a new in vivo experimental model of alcoholic acute
pancreatitis, revealing a specific enzyme target for ethanol-induced injury.
Strategies that prevent FAEE synthesis, protect mitochondria, reduce calcium
overload or sustain calcium homeostasis by ATP provision may provide promising
therapeutic avenues for the treatment of alcoholic acute pancreatitis.
PMID- 25845856
TI - Pancreatic cancer: The microenvironment needs attention too!
AB - The abundant stromal/desmoplastic reaction, a characteristic feature of a
majority of pancreatic adenocarcinomas (PDAC), has only recently been receiving
some attention regarding its possible role in the pathobiology of pancreatic
cancer. It is now well established that the cells predominantly responsible for
producing the collagenous stroma are pancreatic stellate cells (PSCs). In
addition to extracellular matrix proteins, the stroma also exhibits cellular
elements including, immune cells, endothelial cells and neural cells. Evidence is
accumulating to indicate the presence of significant interactions between PSCs
and cancer cells as well as between PSCs and other cell types in the stroma. The
majority of research reports to date, using in vitro and in vivo approaches,
suggest that these interactions facilitate local growth as well as distant
metastasis of pancreatic cancer, although a recent study using animals depleted
of myofibroblasts has raised some questions regarding the central role of
myofibroblasts in cancer progression. Nonetheless, novel therapeutic strategies
have been assessed, mainly in the pre-clinical setting, in a bid to interrupt
stromal-tumour interactions and inhibit disease progression. The next important
challenge is for the translation of such pre-clinical strategies to the clinical
situation so as to improve the outcome of patients with pancreatic cancer.
PMID- 25845857
TI - Feasibility of Lung Volume Recruitment in Early Neuromuscular Weakness: A
Comparison Between Amyotrophic Lateral Sclerosis, Myotonic Dystrophy, and
Postpolio Syndrome.
AB - BACKGROUND: Lung volume recruitment (LVR) is a cough assistance technique used in
persons with neuromuscular disorders (NMDs), most typically in those requiring
noninvasive ventilation (NIV). Whether it may be useful in persons with NMDs who
have milder respiratory impairment is unknown. OBJECTIVE: To assess the
feasibility, impact on quality of life (QOL), and preliminary physiological
effects of daily LVR in different categories of persons with NMDs who have an
early stage of respiratory impairment. DESIGN: Feasibility study. SETTING:
Academic tertiary care center. PARTICIPANTS: Outpatients diagnosed with
amyotrophic lateral sclerosis (n = 8), postpolio syndrome (n = 10), and myotonic
dystrophy (n = 6) who had restrictive respiratory defects but were not yet using
NIV. METHODS: Participants were asked to perform LVR up to 4 times daily and log
their LVR use in a diary. Physiological measurements and questionnaires were
completed at baseline and after 3 months. MAIN OUTCOME MEASUREMENTS: Compliance
with LVR use was assessed, along with QOL and willingness to continue the
treatment. Physiological measurements included forced vital capacity (FVC), lung
insufflation capacity (LIC), and the LIC minus FVC difference. RESULTS: Of the 24
recruited subjects, 7 with amyotrophic lateral sclerosis, 7 with postpolio
syndrome, and 5 with myotonic dystrophy completed the study (n = 19). At
baseline, mean values for FVC and spontaneous peak cough flow were 59.9%
predicted and 373.1 L/min, respectively. For subjects completing the study, 74%
were willing to continue long-term LVR use, and QOL scores were not adversely
affected by LVR in any NMD subgroup. The LIC-FVC difference increased from
baseline to follow-up by a mean of 0.243 L (P = .006) in all subjects (n = 19),
suggesting a possible improvement in respiratory system mechanics. CONCLUSIONS:
In patients with NMDs who have early restrictive respiratory defects but do not
yet require NIV, regular use of LVR is feasible with no negative impact on QOL
over a 3-month period and may have physiological benefits. Further work is needed
to determine whether early institution of LVR can improve respiratory system
mechanics and help delay ventilatory failure in persons with NMDs.
PMID- 25845858
TI - Conflicts of Interest in Medical Technology Markets: Evidence from Orthopedic
Surgery.
AB - Financial relationships between physicians and industry are vital to biomedical
innovation yet create the potential for conflicts of interest in medical
practice. I consider an inducement model of the role of financial relationships
in health care markets, where consulting payments induce physicians to use more
devices of the firms that sponsor them. To test the model, I exploit a policy
shock, whereby government monitoring of payments to joint replacement surgeons
resulted in declines of over 60% in both total payments and in the number of
physicians receiving payments from 2007 to 2008. Using hospital discharge data
from three states, I find that the loss of payments leads physicians to switch 7
percentage points of their device utilization from their sponsoring firms'
devices to other firms' devices, an effect which is concentrated among surgeons
with low switching costs. These results offer support for the inducement model. I
also find evidence of an increase in medical productivity following the policy
intervention, which suggests conditions under which regulation of financial
relationships would be socially beneficial. Copyright (c) 2015 John Wiley & Sons,
Ltd.
PMID- 25845859
TI - Characterization of multiple constituents in Kai-Xin-San prescription and rat
plasma after oral administration by liquid chromatography with quadrupole time-of
flight tandem mass spectrometry.
AB - A sensitive and reliable ultra high performance liquid chromatography coupled
with quadrupole-time-of-flight mass spectrometry method was established to
separate and identify the chemical constituents of Kai-Xin-San prescription, a
classic traditional Chinese medicine formula that plays an important role in the
treatment of Alzheimer's disease. The detection was performed on an Agilent 6520
Accurate-Mass quadrupole time-of-flight mass spectrometer equipped with an
electrospray ionization source in negative modes. With the optimized conditions,
a total of 54 compounds were identified or tentatively characterized. Out of the
54 compounds, six compounds were identified by comparing the retention time and
mass spectrometry data with reference standards, the rest were characterized by
analyzing mass spectrometry data and retrieving the literature data. Results
indicated ginsenosides, polygala saponins, terpenoids, and oligosaccharide esters
were the major effective constituents in Kai-Xin-San prescription. There were 26
prototype ingredients that were assigned for identification in rat plasma. It is
also concluded that the developed ultra high performance liquid chromatography
coupled with quadrupole-time-of-flight mass spectrometry method with high
sensitivity and resolution is suitable for identifying and characterizing the
chemical constituents of Kai-Xin-San prescription, and the analysis provides a
helpful chemical basis for further research on Kai-Xin-San prescription and the
clinical diagnostics of Alzheimer's disease.
PMID- 25845860
TI - The sheep as a model of preclinical safety and pharmacokinetic evaluations of
candidate microbicides.
AB - When developing novel microbicide products for the prevention of HIV infection,
the preclinical safety program must evaluate not only the active pharmaceutical
ingredient but also the product itself. To that end, we applied several
relatively standard toxicology study methodologies to female sheep, incorporating
an assessment of the pharmacokinetics, safety, tolerability, and local toxicity
of a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal
Ring-004). We performed a 3-month general toxicology study, a preliminary
pharmacokinetic study using drug-loaded vaginal gel, and a detailed assessment of
the kinetics of dapivirine delivery to plasma, vaginal, and rectal fluid and
rectal, vaginal, and cervical tissue over 28 days of exposure and 3 and 7 days
after removal of the ring. The findings of the general toxicology study supported
the existing data from both preclinical and clinical studies in that there were
no signs of toxicity related to dapivirine. In addition, the presence of the
physical dapivirine ring did not alter local or systemic toxicity or the
pharmacokinetics of dapivirine. Pharmacokinetic studies indicated that the
dapivirine ring produced significant vaginal tissue levels of dapivirine.
However, no dapivirine was detected in cervical tissue samples using the methods
described here. Plasma and vaginal fluid levels were lower than those in previous
clinical studies, while there were detectable dapivirine levels in the rectal
tissue and fluid. All tissue and fluid levels tailed off rapidly to undetectable
levels following removal of the ring. The sheep represents a very useful model
for the assessment of the safety and pharmacokinetics of microbicide drug
delivery devices, such as the vaginal ring.
PMID- 25845861
TI - Ceftazidime-avibactam activity against multidrug-resistant Pseudomonas aeruginosa
isolated in U.S. medical centers in 2012 and 2013.
AB - Pseudomonas aeruginosa isolates (n = 3,902) from 75 U.S. medical centers were
tested against ceftazidime-avibactam and comparator agents by the reference broth
microdilution method. Overall, 96.9% of the strains were susceptible (MIC, <=8
MUg/ml) to ceftazidime-avibactam, while the rates of susceptibility for
ceftazidime, meropenem, and piperacillin-tazobactam were 83.8, 81.9, and 78.5%,
respectively. Multidrug-resistant and extensively drug-resistant phenotypes were
observed in 14.9 and 8.7% of the strains, respectively, and 81.0 and 73.7% of the
strains were susceptible to ceftazidime-avibactam, respectively.
PMID- 25845862
TI - Ceftazidime-avibactam activity tested against Enterobacteriaceae isolates from
U.S. hospitals (2011 to 2013) and characterization of beta-lactamase-producing
strains.
AB - Ceftazidime-avibactam (MIC50/90, 0.12/0.25 MUg/ml) inhibited 99.9%
(20,698/20,709) of Enterobacteriaceae isolates at <=8 MUg/ml. This compound was
active against resistant subsets, including ceftazidime-nonsusceptible
Enterobacter cloacae (MIC50/90, 0.25/0.5 MUg/ml) and extended-spectrum beta
lactamase (ESBL) phenotype isolates. An ESBL phenotype was noted among 12.4%
(1,696/13,692 isolates from targeted species) of the isolates, including 776
Escherichia coli (12.0% for this species; MIC50/90, 0.12/0.25 MUg/ml), 721
Klebsiella pneumoniae (16.3%; MIC50/90, 0.12/0.25 MUg/ml), 119 Klebsiella oxytoca
(10.3%; MIC50/90, 0.06/0.25 MUg/ml), and 80 Proteus mirabilis (4.9%; MIC50/90,
0.06/0.12 MUg/ml) isolates. The most common enzymes detected among ESBL phenotype
isolates from 2013 (n = 743) screened using a microarray-based assay were CTX-M
15-like (n = 307), KPC (n = 120), SHV ESBLs (n = 118), and CTX-M-14-like (n =
110). KPC producers were highly resistant to comparators, and ceftazidime
avibactam (MIC50/90, 0.5/2 MUg/ml) and tigecycline (MIC50/90, 0.5/1 MUg/ml; 98.3%
susceptible) were the most active agents against these strains. Meropenem
(MIC50/90, <=0.06/<=0.06 MUg/ml) and ceftazidime-avibactam (MIC50/90, 0.12/0.25
MUg/ml) were active against CTX-M-producing isolates. Other enzymes were also
observed, and ceftazidime-avibactam displayed good activity against the isolates
producing less common enzymes. Among 11 isolates displaying ceftazidime-avibactam
MIC values of >8 MUg/ml, three were K. pneumoniae strains producing metallo-beta
lactamases (all ceftazidime-avibactam MICs, >32 MUg/ml), with two NDM-1 producers
and one K. pneumoniae strain carrying the bla(KPC-2) and bla(VIM-4) genes.
Therapeutic options for isolates producing beta-lactamases may be limited, and
ceftazidime-avibactam, which displayed good activity against strains, including
those producing KPC enzymes, merits further study in infections where such
organisms occur.
PMID- 25845863
TI - Fast hepatitis C virus RNA elimination and NS5A redistribution by NS5A inhibitors
studied by a multiplex assay approach.
AB - While earlier therapeutic strategies for the treatment of hepatitis C virus (HCV)
infection relied exclusively on interferon (IFN) and ribavirin (RBV), four direct
acting antiviral agents (DAAs) have now been approved, aiming for an interferon
free strategy with a short treatment duration and fewer side effects. To
facilitate studies on the mechanism of action (MOA) and efficacy of DAAs, we
established a multiplex assay approach, which employs flow cytometry, a Gaussia
luciferase reporter system, Western blot analysis, reverse transcription
quantitative PCR (RT-qPCR), a limited dilution assay (50% tissue culture
infectious dose [TCID50]), and an image profiling assay that follows the NS5A
redistribution in response to drug treatment. We used this approach to compare
the relative potency of various DAAs and the kinetics of their antiviral effects
as a potential preclinical measure of their potential clinical utility. We
evaluated the NS5A inhibitors ledipasvir (LDV) and daclatasvir (DCV), the NS3/4A
inhibitor danoprevir (DNV), and the NS5B inhibitor sofosbuvir (SOF). In terms of
kinetics, our data demonstrate that the NS5A inhibitor LDV, followed closely by
DCV, has the fastest effect on suppression of viral proteins and RNA and on
redistribution of NS5A. In terms of MOA, LDV has a more pronounced effect than
DCV on the viral replication, assembly, and infectivity of released virus. Our
approach can be used to facilitate the study of the biological processes involved
in HCV replication and help identify optimal drug combinations.
PMID- 25845864
TI - A thorough QT study to evaluate the effects of therapeutic and supratherapeutic
doses of delafloxacin on cardiac repolarization.
AB - A randomized, double-blind, placebo-controlled, 4-period crossover study was
conducted in 52 healthy adults to assess the effect of delafloxacin on the
corrected QT (QTc) interval. The QT interval, corrected for heart rate using
Fridericia's formula (QTcF), was determined predose and at 0.5, 1, 1.25, 1.5,
1.75, 2, 2.5, 3, 4, 5, 6, 12, 18, and 24 h after dosing with delafloxacin at 300
mg intravenously (i.v.; therapeutic), delafloxacin at 900 mg i.v.
(supratherapeutic), moxifloxacin at 400 mg orally (p.o.; positive control), and
placebo. The pharmacokinetic profile of delafloxacin was also evaluated. At each
time point after delafloxacin administration, the upper limit of the 90%
confidence interval (CI) for the placebo-corrected change from the predose
baseline in QTcF (DeltaDeltaQTcF) was less than 10 ms (maximum, 3.9 ms at 18 h
after dosing), indicating an absence of a clinically meaningful increase in the
QTc interval. The lower limit of the 90% CI of DeltaDeltaQTcF for moxifloxacin
versus placebo was longer than 5 ms at all 5 time points selected for assay
sensitivity analysis, demonstrating that the study was adequately sensitive to
assess QTc prolongation. There was no positive relationship between delafloxacin
plasma concentrations and DeltaDeltaQTcF. Treatment-emergent adverse events (AEs)
were more frequent among subjects receiving a single supratherapeutic dose of 900
mg delafloxacin. There were no deaths, serious AEs, or AEs leading to study
discontinuation and no clinically meaningful abnormalities in laboratory values
or vital signs observed at any time point after any dose of the study drug.
PMID- 25845865
TI - In vivo pharmacokinetic/pharmacodynamic profiles of valnemulin in an experimental
intratracheal Mycoplasma gallisepticum infection model.
AB - Valnemulin, a semisynthetic pleuromutilin antibiotic derivative, is greatly
active against Mycoplasma. The objective of our study was to evaluate the
effectiveness of valnemulin against Mycoplasma gallisepticum in a neutropenic
intratracheal model in chickens using a pharmacokinetic/pharmacodynamic (PK-PD)
method. The PK of valnemulin after intramuscular (i.m.) administration at doses
of 1, 10, and 20 mg/kg of body weight in M. gallisepticum-infected neutropenic
chickens was evaluated by liquid chromatography-tandem mass spectrometry (LC
MS/MS). Real-time PCR (RT-PCR) was used for quantitative detection of M.
gallisepticum. The ratio of the 24-h area under the concentration-time curve
divided by the MIC (AUC24/MIC) correlated well with the in vivo antibacterial
effectiveness of valnemulin (R(2) = 0.9669). The AUC24/MIC ratios for
mycoplasmastasis (a reduction of 0 log10 color-changing unit [CCU]
equivalents/ml), a reduction of 1 log10 CCU equivalents/ml, and a reduction of
2.5 log10 CCU equivalents/ml are 28,820, 38,030, and 56,256, respectively. In
addition, we demonstrated that valnemulin at a dose of 6.5 mg/kg resulted in a
reduction of 2.5 log10 CCU equivalents/ml. These investigations provide a solid
foundation for the usage of valnemulin in poultry with M. gallisepticum
infections.
PMID- 25845866
TI - Kibdelomycin is a bactericidal broad-spectrum aerobic antibacterial agent.
AB - Bacterial resistance to antibiotics continues to grow and pose serious
challenges, while the discovery rate for new antibiotics declines. Kibdelomycin
is a recently discovered natural-product antibiotic that inhibits bacterial
growth by inhibiting the bacterial DNA replication enzymes DNA gyrase and
topoisomerase IV. It was reported to be a broad-spectrum aerobic Gram-positive
agent with selective inhibition of the anaerobic bacterium Clostridium difficile.
We have extended the profiling of kibdelomycin by using over 196 strains of Gram
positive and Gram-negative aerobic pathogens recovered from worldwide patient
populations. We report the MIC50s, MIC90s, and bactericidal activities of
kibdelomycin. We confirm the Gram-positive spectrum and report for the first time
that kibdelomycin shows strong activity (MIC90, 0.125 MUg/ml) against clinical
strains of the Gram-negative nonfermenter Acinetobacter baumannii but only weak
activity against Pseudomonas aeruginosa. We confirm that well-characterized
resistant strains of Staphylococcus aureus and Streptococcus pneumoniae show no
cross-resistance to kibdelomycin and quinolones and coumarin antibiotics. We also
show that kibdelomycin is not subject to efflux in Pseudomonas, though it is in
Escherichia coli, and it is generally affected by the outer membrane permeability
entry barrier in the nonfermenters P. aeruginosa and A. baumannii, which may be
addressable by structure-based chemical modification.
PMID- 25845867
TI - Open-label, single-dose, parallel-group study in healthy volunteers to determine
the drug-drug interaction potential between KAE609 (cipargamin) and piperaquine.
AB - KAE609 represents a new class of potent, fast-acting, schizonticidal
antimalarials. This study investigated the safety and pharmacokinetics of KAE609
in combination with the long-acting antimalarial piperaquine (PPQ) in healthy
volunteers. A two-way pharmacokinetic interaction was hypothesized for KAE609 and
PPQ, as both drugs are CYP3A4 substrates and inhibitors. The potential for both
agents to affect the QT interval was also assessed. This was an open-label,
parallel-group, single-dose study with healthy volunteers. Subjects were
randomized to four parallel dosing arms with five cohorts (2:2:2:2:1), receiving
75 mg KAE609 plus 320 mg PPQ, 25 mg KAE609 plus 1,280 mg PPQ, 25 mg KAE609 alone,
320 mg PPQ alone, or 1,280 mg PPQ alone. Triplicate electrocardiograms were
performed over the first 24 h after dosing, with single electrocardiograms at
other time points. Routine safety (up to 89 days) and pharmacokinetic (up to 61
days) assessments were performed. Of the 110 subjects recruited, 99 completed the
study. Coadministration of PPQ had no overall effect on exposure to KAE609,
although 1,280 mg PPQ decreased the KAE609 maximum concentration (Cmax) by 17%.
The group that received 25 mg KAE609 plus 1,280 mg PPQ showed a 32% increase in
the PPQ area under the concentration-time curve from 0 to infinity (AUCinf),
while the group that received 75 mg KAE609 plus 320 mg PPQ showed a 14%
reduction. Mean changes from baseline in the QT interval corrected by
Fridericia's method (QTcF) and the QT interval corrected by Bazett's method
(QTcB) with PPQ were consistent with its known effects. PPQ but not KAE609
exposure correlated with corrected QT interval (QTc) increases, and KAE609 did
not affect the PPQ exposure-QTc relationship. The QTcF effect for PPQ (least
squares estimate of the difference in mean maximal changes from baseline of 7.47
ms [90% confidence interval, 3.55 to 11.4 ms]) was consistent with the criteria
for a positive thorough QT study. No subject had QTcF or QTcB values of >500 ms.
Both drugs given alone or in combination were well tolerated, with no deaths,
serious adverse events (AEs), or severe AEs reported. Most AEs were mild; upper
respiratory tract infections, headache, diarrhea, and oropharyngeal pain were
most common. PPQ and KAE609 coadministration had no relevant effect on exposure
to either agent, and KAE609 did not affect or potentiate the known effects of PPQ
on cardiac conduction.
PMID- 25845868
TI - Homology modeling of NAD+-dependent DNA ligase of the Wolbachia endosymbiont of
Brugia malayi and its drug target potential using dispiro-cycloalkanones.
AB - Lymphatic filarial nematodes maintain a mutualistic relationship with the
endosymbiont Wolbachia. Depletion of Wolbachia produces profound defects in
nematode development, fertility, and viability and thus has great promise as a
novel approach for treating filarial diseases. NAD(+)-dependent DNA ligase is an
essential enzyme of DNA replication, repair, and recombination. Therefore, in the
present study, the antifilarial drug target potential of the NAD(+)-dependent DNA
ligase of the Wolbachia symbiont of Brugia malayi (wBm-LigA) was investigated
using dispiro-cycloalkanone compounds. Dispiro-cycloalkanone specifically
inhibited the nick-closing and cohesive-end ligation activities of the enzyme
without inhibiting human or T4 DNA ligase. The mode of inhibition was competitive
with the NAD(+) cofactor. Docking studies also revealed the interaction of these
compounds with the active site of the target enzyme. The adverse effects of these
inhibitors were observed on adult and microfilarial stages of B. malayi in vitro,
and the most active compounds were further monitored in vivo in jirds and
mastomys rodent models. Compounds 1, 2, and 5 had severe adverse effects in vitro
on the motility of both adult worms and microfilariae at low concentrations.
Compound 2 was the best inhibitor, with the lowest 50% inhibitory concentration
(IC50) (1.02 MUM), followed by compound 5 (IC50, 2.3 MUM) and compound 1 (IC50,
2.9 MUM). These compounds also exhibited the same adverse effect on adult worms
and microfilariae in vivo (P < 0.05). These compounds also tremendously reduced
the wolbachial load, as evident by quantitative real-time PCR (P < 0.05). wBm
LigA thus shows great promise as an antifilarial drug target, and dispiro
cycloalkanone compounds show great promise as antifilarial lead candidates.
PMID- 25845869
TI - Mutations in the bacterial ribosomal protein l3 and their association with
antibiotic resistance.
AB - Different groups of antibiotics bind to the peptidyl transferase center (PTC) in
the large subunit of the bacterial ribosome. Resistance to these groups of
antibiotics has often been linked with mutations or methylations of the 23S rRNA.
In recent years, there has been a rise in the number of studies where mutations
have been found in the ribosomal protein L3 in bacterial strains resistant to PTC
targeting antibiotics but there is often no evidence that these mutations
actually confer antibiotic resistance. In this study, a plasmid exchange system
was used to replace plasmid-carried wild-type genes with mutated L3 genes in a
chromosomal L3 deletion strain. In this way, the essential L3 gene is available
for the bacteria while allowing replacement of the wild type with mutated L3
genes. This enables investigation of the effect of single mutations in
Escherichia coli without a wild-type L3 background. Ten plasmid-carried mutated
L3 genes were constructed, and their effect on growth and antibiotic
susceptibility was investigated. Additionally, computational modeling of the
impact of L3 mutations in E. coli was used to assess changes in 50S structure and
antibiotic binding. All mutations are placed in the loops of L3 near the PTC.
Growth data show that 9 of the 10 mutations were well accepted in E. coli,
although some of them came with a fitness cost. Only one of the mutants exhibited
reduced susceptibility to linezolid, while five exhibited reduced susceptibility
to tiamulin.
PMID- 25845870
TI - Praziquantel in a clay nanoformulation shows more bioavailability and higher
efficacy against murine Schistosoma mansoni infection.
AB - Consideration of existing compounds always simplifies and shortens the long and
difficult process of discovering new drugs specifically for diseases of
developing countries, an approach that may add to the significant potential cost
savings. This study focused on improving the biological characteristics of the
already-existing antischistosomal praziquantel (PZQ) by incorporating it into
montmorillonite (MMT) clay as a delivery carrier to overcome its known
bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay
nanoformulation and its in vivo efficacy against Schistosoma mansoni were
investigated. The PZQ-MMT clay nanoformulation provided a preparation with a
controlled release rate, a decrease in crystallinity, and an appreciable
reduction in particle size. Uninfected and infected mice treated with PZQ-MMT
clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively,
in area under the concentration-time curve from 0 to 8 h (AUC0-8) and maximum
concentration of drug in serum (Cmax), with a decrease in elimination rate
constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate
constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34
fold, respectively, versus the corresponding conventional PZQ-treated groups.
This improved bioavailability has been expressed in higher efficacy of the drug,
where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50%
effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to
74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg
load and increase in total immature, mature, and dead eggs in most of the drug
treated groups. This formulation showed better bioavailability, enhanced
antischistosomal efficacy, and a safer profile despite the longer period of
residence in the systemic circulation. Although the conventional drug's toxicity
was not examined, animal mortality rates were not different between groups
receiving the test PZQ-clay nanoformulation and conventional PZQ.
PMID- 25845871
TI - Colonization of extended-spectrum-beta-lactamase- and NDM-1-producing
Enterobacteriaceae among pregnant women in the community in a low-income country:
a potential reservoir for transmission of multiresistant Enterobacteriaceae to
neonates.
AB - The spread of extended-spectrum-beta-lactamase-producing Enterobacteriaceae (ESBL
PE) in low-income countries, where the burden of neonatal sepsis is high, may
have a serious impact on neonatal mortality rates. Given the potential for mother
to-child transmission of multiresistant bacteria, this study investigated the
ESBL-PE rectal colonization among pregnant women at delivery in the community in
Madagascar and estimated a prevalence of 18.5% (95% confidence interval, 14.5% to
22.6%). One strain of Klebsiella pneumoniae isolated was also a New Delhi metallo
beta-lactamase-1 (NDM-1) producer.
PMID- 25845872
TI - Impact of combination antimicrobial therapy on mortality risk for critically ill
patients with carbapenem-resistant bacteremia.
AB - There are limited treatment options for carbapenem-resistant Gram-negative
infections. Currently, there are suggestions in the literature that combination
therapy should be used, which frequently includes antibiotics to which the
causative pathogen demonstrates in vitro resistance. This case-control study
evaluated risk factors associated with all-cause mortality rates for critically
ill patients with carbapenem-resistant Gram-negative bacteremia. Adult patients
who were admitted to an intensive care unit with sepsis and a blood culture
positive for Gram-negative bacteria resistant to a carbapenem were included.
Patients with polymicrobial, recurrent, or breakthrough infections were excluded.
Included patients were classified as survivors (controls) or nonsurvivors (cases)
at 30 days after the positive blood culture. Of 302 patients screened, 168
patients were included, of whom 90 patients died (53.6% [cases]) and 78 survived
(46.4% [controls]) at 30 days. More survivors received appropriate antibiotics
(antibiotics with in vitro activity) than did nonsurvivors (93.6% versus 53.3%; P
< 0.01). Combination therapy, defined as multiple appropriate agents given for 48
h or more, was more common among survivors than nonsurvivors (32.1% versus 7.8%;
P < 0.01); however, there was no difference in multiple-agent use when in vitro
activity was not considered (including combinations with carbapenems) (87.2%
versus 80%; P = 0.21). After adjustment for baseline factors with multivariable
logistic regression, combination therapy was independently associated with
decreased risk of death (odds ratio, 0.19 [95% confidence interval, 0.06 to
0.56]; P < 0.01). These data suggest that combination therapy with multiple
agents with in vitro activity is associated with improved survival rates for
critically ill patients with carbapenem-resistant Gram-negative bacteremia.
However, that association is lost if in vitro activity is not considered.
PMID- 25845873
TI - Pharmacokinetics of dolutegravir in a premature neonate after HIV treatment
intensification during pregnancy.
AB - We describe the pharmacokinetics of dolutegravir (DTG) in a premature neonate
after maternal intensification of an antiretroviral (ARV) regimen by adding DTG.
During the last 2 weeks of pregnancy, the ARV was tenofovir-emtricitabine,
atazanavir-ritonavir, and DTG (50 mg once daily). From the interaction between
atazanavir and DTG via CYP3A4 and UGT1A1 and placental efflux transporter
inhibition and considering the infant's probable enzymatic immaturity, the DTG
elimination half-life was estimated to be 4-fold longer in neonates than in
adults.
PMID- 25845874
TI - Enantiomers of nifurtimox do not exhibit stereoselective anti-Trypanosoma cruzi
activity, toxicity, or pharmacokinetic properties.
AB - With the aim of improving the available drugs for the treatment of Chagas
disease, individual enantiomers of nifurtimox were characterized. The results
indicate that the enantiomers are equivalent in their in vitro activity against a
panel of Trypanosoma cruzi strains; in vivo efficacy in a murine model of Chagas
disease; in vitro toxicity and absorption, distribution, metabolism, and
excretion characteristics; and in vivo pharmacokinetic properties. There is
unlikely to be any therapeutic benefit of an individual nifurtimox enantiomer
over the racemic mixture.
PMID- 25845875
TI - Clinical and microbiologic analysis of the risk factors for mortality in patients
with heterogeneous vancomycin-intermediate Staphylococcus aureus bacteremia.
AB - The prevalence of the heterogeneous vancomycin-intermediate Staphylococcus aureus
(hVISA) phenotype among methicillin-resistant S. aureus (MRSA) blood isolates can
reach 38%. hVISA bacteremia is known to be associated with vancomycin treatment
failure, including persistent bacteremia. We conducted this study to evaluate
risk factors for 12-week mortality in patients with hVISA bacteremia through a
detailed clinical and microbiological analysis of a prospective cohort of
patients with S. aureus bacteremia. All isolates were collected on the first day
of bacteremia and subjected to population analysis profiling for hVISA detection,
genotyping, and PCR analysis for 39 virulence factors. Of 382 patient with MRSA
bacteremia, 121 (32%) had hVISA bacteremia. Deceased patients were more likely to
have hematologic malignancy (P = 0.033), ultimately or rapidly fatal disease (P =
0.007), and a higher Pitt bacteremia score (P = 0.010) than surviving patients.
The sequence type 239 (ST239) clonal type and definitive linezolid treatment were
associated with a trend toward reduced mortality (P = 0.061 and 0.072,
respectively), but a high vancomycin MIC (>=2 mg/liter) was not associated with
increased mortality (P = 0.368). In a multivariate analysis, ultimately or
rapidly fatal disease (adjusted odds ratio [aOR], 2.80; 95% confidence interval
[CI], 1.14 to 6.85) and a high Pitt bacteremia score (aOR, 1.26; 95% CI, 1.07 to
1.48) were independent risk factors for mortality. Hematologic malignancy was
associated with a trend toward increased mortality (P = 0.094), and ST239 was
associated with a trend toward reduced mortality (P = 0.095). Our study suggests
that ST239 hVISA is a possible predictor of survival in hVISA bacteremia.
PMID- 25845876
TI - A pantetheinase-resistant pantothenamide with potent, on-target, and selective
antiplasmodial activity.
AB - Pantothenamides inhibit blood-stage Plasmodium falciparum with potencies (50%
inhibitory concentration [IC50], ~20 nM) similar to that of chloroquine. They
target processes dependent on pantothenate, a precursor of the essential
metabolic cofactor coenzyme A. However, their antiplasmodial activity is reduced
due to degradation by serum pantetheinase. Minor modification of the
pantothenamide structure led to the identification of alpha-methyl-N-phenethyl
pantothenamide, a pantothenamide resistant to degradation, with excellent
antiplasmodial activity (IC50, 52 +/- 6 nM), target specificity, and low
toxicity.
PMID- 25845877
TI - Characterization of multiple NDM-1-producing Enterobacteriaceae isolates from the
same patient.
AB - A male patient was admitted to a community hospital in Ontario, Canada, with an
infected sacral ulcer after returning from India, where he was hospitalized.
Carbapenem-resistant Escherichia coli (isolated from blood cultures),
Enterobacter cloacae, and Providencia stuartii (from urine samples), all positive
for bla(NDM-1), were recovered. Comparative NDM-1 plasmid analysis suggests both
lateral plasmid transfer and independent acquisition of the bla(NDM-1) gene in
these clinical isolates.
PMID- 25845878
TI - Profiling of beta-lactam selectivity for penicillin-binding proteins in
Streptococcus pneumoniae D39.
AB - Selective fluorescent beta-lactam chemical probes enable the visualization of the
transpeptidase activity of penicillin-binding proteins (PBPs) at different stages
of bacterial cell division. To facilitate the development of new fluorescent
probes for PBP imaging, we evaluated 20 commercially available beta-lactams for
selective PBP inhibition in an unencapsulated derivative of the D39 strain of
Streptococcus pneumoniae. Live cells were treated with beta-lactam antibiotics at
different concentrations and subsequently incubated with Bocillin FL (Boc-FL;
fluorescent penicillin) to saturate uninhibited PBPs. Fluorophore-labeled PBPs
were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
PAGE) and fluorescence scanning. Among 20 compounds tested, carbapenems
(doripenem and meropenem) were coselective for PBP1a, PBP2x, and PBP3, while six
of the nine penicillin compounds were coselective for PBP2x and PBP3. In
contrast, the seven cephalosporin compounds tested display variability in their
PBP-binding profiles. Three cephalosporin compounds (cefoxitin, cephalexin, and
cefsulodin) and the monobactam aztreonam exhibited selectivity for PBP3, while
only cefuroxime (a cephalosporin) was selective for PBP2x. Treatment of S.
pneumoniae cultures with a sublethal concentration of cefuroxime that inhibited
60% of PBP2x activity and less than 20% of the activity of other PBPs resulted in
formation of elongated cells. In contrast, treatment of S. pneumoniae cultures
with concentrations of aztreonam and cefoxitin that inhibited up to 70% of PBP3
activity and less than 30% of other PBPs resulted in no discernible morphological
changes. Additionally, correlation of the MIC and IC50s for each PBP, with the
exception of faropenem, amdinocillin (mecillinam), and 6-APA, suggests that
pneumococcal growth inhibition is primarily due to the inhibition of PBP2x.
PMID- 25845879
TI - Ibuprofen potentiates the in vivo antifungal activity of fluconazole against
Candida albicans murine infection.
AB - Candida albicans is the most prevalent cause of fungemia worldwide. Its ability
to develop resistance in patients receiving azole antifungal therapy is well
documented. In a murine model of systemic infection, we show that ibuprofen
potentiates fluconazole antifungal activity against a fluconazole-resistant
strain, drastically reducing the fungal burden and morbidity. The therapeutic
combination of fluconazole with ibuprofen may constitute a new approach for the
management of antifungal therapeutics to reverse the resistance conferred by
efflux pump overexpression.
PMID- 25845880
TI - Commensal streptococci serve as a reservoir for beta-lactam resistance genes in
Streptococcus pneumoniae.
AB - Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, septicemia,
and middle ear infections. The incidence of S. pneumoniae isolates that are not
susceptible to penicillin has risen worldwide and may be above 20% in some
countries. Beta-lactam antibiotic resistance in pneumococci is associated with
significant sequence polymorphism in penicillin-binding proteins (PBPs).
Commensal streptococci, especially S. mitis and S. oralis, have been identified
as putative donors of mutated gene fragments. However, no studies have compared
sequences of the involved pbp genes in large collections of commensal
streptococci with those of S. pneumoniae. We therefore investigated the sequence
diversity of the transpeptidase region of the three pbp genes, pbp2x, pbp2b, and
pbp1a in 107, 96, and 88 susceptible and nonsusceptible strains of commensal
streptococci, respectively, at the nucleotide and amino acid levels to determine
to what extent homologous recombination between commensal streptococci and S.
pneumoniae plays a role in the development of beta-lactam resistance in S.
pneumoniae. In contrast to pneumococci, extensive sequence variation in the
transpeptidase region of pbp2x, pbp2b, and pbp1a was observed in both susceptible
and nonsusceptible strains of commensal streptococci, conceivably reflecting the
genetic diversity of the many evolutionary lineages of commensal streptococci
combined with the recombination events occurring with intra- and interspecies
homologues. Our data support the notion that resistance to beta-lactam
antibiotics in pneumococci is due to sequences acquired from commensal Mitis
group streptococci, especially S. mitis. However, several amino acid alterations
previously linked to beta-lactam resistance in pneumococci appear to represent
species signatures of the donor strain rather than being causal of resistance.
PMID- 25845881
TI - Etest cannot be recommended for in vitro susceptibility testing of mucorales.
AB - Amphotericin B and posaconazole susceptibility patterns were determined for the
most prevalent Mucorales, following EUCAST (European Committee on Antimicrobial
Susceptibility Testing) broth microdilution guidelines. In parallel, Etest was
performed and evaluated against EUCAST. The overall agreement of MICs gained with
Etest and EUCAST was 75.1%; therefore, Etest cannot be recommended for antifungal
susceptibility testing of Mucorales. Amphotericin B was the most active drug
against Mucorales species in vitro, while the activities of posaconazole were
more restricted.
PMID- 25845882
TI - Analysis of the human osseous nasal shape--population differences and sexual
dimorphism.
AB - OBJECTIVES: In this study, the shape of the outer osseous nose in a German and a
Chinese sample is analyzed using a dense set of semi-landmarks. Shape differences
related to population and sex as well as directional and fluctuating asymmetry
were statistically evaluated and also visualized. MATERIALS AND METHODS: Shape
differences in the bony nose were investigated between a large sample of CT scans
of German (140 ?, 127 ?) and Chinese (135 ?, 132 ?) crania. We used semi
automatic methods to represent the shape of this region as a dense point-cloud,
consisting of 370 three-dimensional bilateral coordinates. Both the symmetric and
asymmetric modes of shape variation were addressed. RESULTS: Strong differences
in nasal shape were found between the two populations, while sex was found to
play a minor role in explaining the observed shape variation. The expression of
sexual dimorphism was similar in both populations. Differences attributed to
population affinity and to sexual dimorphism were both found to affect the shape
of the ossa nasalia and the projection of the spina nasalis. The correlation with
population/sex was weak for directional asymmetry, but strong for fluctuating
asymmetry. The nasal region is more asymmetric in Germans than in Chinese, with
males displaying more asymmetry than females in both populations. DISCUSSION:
While the bony nose is well suited for predicting population affinity, regarding
the populations under investigation, its value for sexing unknown individuals is
rather moderate. The similar expression of sexual dimorphism in those otherwise
very dissimilar populations indicates common factors responsible for these
differences.
PMID- 25845883
TI - Simple thiol-ene click chemistry modification of SBA-15 silica pores with
carboxylic acids.
AB - A straightforward approach for anchoring tailored carboxylic groups in mesoporous
SiO2 colloidal materials is presented. The thiol-ene photochemical reaction
between vinyltrimethoxysilane precursors and various thiocarboxylic acids which
has, click chemistry features (i.e. high conversion yields, insensitivity to
oxygen, mild reaction conditions), results in carboxylated silane precursors that
can be readily used as surface modifiers. The carboxylic groups of acetic,
undecanoic and succinic acid were immobilized on the silica mesopore walls of SBA
15 powders employing the synthesized silane precursors. Post-grafting has been
confirmed through infrared spectrometry (FTIR), energy dispersive X-ray
spectroscopy (EDS), elemental analysis (EA) and zeta potential measurements.
Detailed field-emission gun scanning electron microscopy (FESEM) images and small
angle X-ray scattering (SAXS) data revealed parallel mesopores and ordered
mesostructures. It is shown that the immobilized COOH groups are chemically
accessible for acid-base reactions as well as copper adsorption. Immobilization
of easily synthesized tailored carboxylic modified alkoxide precursors within
mesoporous systems provides a unique chemical nanoenvironment within these
ordered frameworks.
PMID- 25845884
TI - A simple way to prepare Pd/Fe3O4/polypyrrole hollow capsules and their
applications in catalysis.
AB - Preparation of catalysts with good catalytic activity and high stability,
together with magnetic separation property, in a simple way is highly desirable.
In this paper, we reported a novel strategy to construct magnetic recyclable
hollow capsules with Pd and Fe3O4 nanoparticles embedded in polypyrrole (PPy)
shell via only two steps: first, synthesization of Pd nanoparticles, preparation
of Fe3O4 nanoparticles, and formation of PPy shell were finished in one-step on
the surface of polystyrene (PS) nanospheres; then, the PS core was selectively
removed by tetrahydrofuran. The Pd/Fe3O4/PPy hollow capsules exhibited good
catalytic property in reduction of 4-nitrophenol with NaBH4 as reducing agent,
and the reaction rate constants were calculated through pseudo-first-order
reaction equation. Due to incorporation of Fe3O4 nanoparticles, the catalysts
could be quickly separated from the reaction solution by magnet and reused
without obvious catalytic loss. Besides catalytic property and reusability, their
stability was also examined by HNO3 etching experiment. Compared with bare Pd and
Fe3O4 nanoparticles, the stability of both Pd and Fe3O4 nanoparticles in hollow
capsules was largely improved owing to the protection of PPy shell. The good
catalytic performance, ease of separation, high stability and especially a simple
preparation procedure, made Pd/Fe3O4/PPy hollow capsules highly promising
candidates for diverse applications.
PMID- 25845886
TI - Seasonal isolation of microalgae from municipal wastewater for remediation and
biofuel applications.
AB - AIMS: The objective of the study was to isolate the microalgae strains from
treated municipal wastewater in both summer and winter seasons in order to
identify strains better suited for nutrient remediation and biofuel production
under either cooler or warmer temperatures. METHODS AND RESULTS: Fifty-six
strains in total were isolated and identified by DNA sequencing from effluent
samples collected from a local wastewater treatment plant during the summer and
winter of 2011. Screening of 41 isolates based on the fatty acid productivity at
either 22 or 10 degrees C resulted in the selection of 12 strains organized into
two groups of 6-the M (mild) and C (cool) groups, respectively. Four of the C
group strains were isolated from the winter sample, while four of the M-group
isolates were isolated from the summer sample. Fatty acid pools in M-group
strains were heavily regulated in response to growth temperature while C-group
strains were more insensitive. In three of the six C-group strains, the rates of
biomass and fatty acid productivity at 10 degrees C exceeded the corresponding
rates at 22 degrees C. Conversely, M group were always more productive at 22
compared to 10 degrees C. Mixotrophic strategies to enhance productivity were
generally unsuccessful in M-group strains at 22 degrees C but proved to be more
effective in C-group cultures at 10 degrees C. CONCLUSIONS: In general, C-group
strains appeared better suited for growth in municipal wastewater at 10 degrees
C, while M-group strains were better suited at 22 degrees C. On balance, C-group
isolates were more likely to come from winter wastewater samples while M-group
strains were more likely to come from the summer sample. SIGNIFICANCE AND IMPACT
OF THE STUDY: Our results demonstrate that the effects of temperature on
microalgal growth for wastewater remediation can be mitigated somewhat by
isolation and careful selection of strains adapted to seasonal wastewater
conditions.
PMID- 25845887
TI - Immune Response Profile against Persistent Endodontic Pathogens Candida albicans
and Enterococcus faecalis In Vitro.
AB - INTRODUCTION: Persistent microorganisms such as Candida albicans and Enterococcus
faecalis might be directly related to endodontic treatment failure. The host
response to these microorganisms impairs the reestablishment of intraradicular
and periradicular health. METHODS: The present investigation evaluated the
expression of inflammatory mediators produced by RAW 264.7 cells in the presence
of heat-killed antigens (HK) C. albicans and E. faecalis. Cultures of RAW cells
were stimulated with both antigens in the presence or absence of recombinant
interferon (rIFN)-gamma. Parameters of cell viability, production of nitric oxide
(NO), as well as the synthesis of interleukin (IL)-1alpha, IL-6, IL-10, IL-12,
monocyte chemotactic protein-1, and tumor necrosis factor (TNF)-alpha were
analyzed. RESULTS: Results demonstrated that cell viability was especially
reduced in antigens and rIFN-gamma-stimulated groups. Groups stimulated with HK
C. albicans upregulated IL-10 production. Otherwise, the addition of rIFN-gamma
to HK C. albicans upregulated TNF-alpha and NO production. Groups stimulated with
HK E. faecalis upregulated TNF-alpha production. HK E. faecalis and rIFN-gamma
upregulated TNF-alpha and NO synthesis. The production of other cytokines
remained unchanged by all stimuli. CONCLUSIONS: Knowledge regarding the host
mechanism of response to microorganisms that perpetuate endodontic infection and
the periradicular lesions can contribute to optimization of endodontic therapy.
The mentioned inflammatory mediators and virulence factors involved in endodontic
failure might guide lesion progression and also be targets in the development of
disinfectant and immunomodulatory agents.
PMID- 25845888
TI - Ruminococcal cellulosome systems from rumen to human.
AB - A cellulolytic fiber-degrading bacterium, Ruminococcus champanellensis, was
isolated from human faecal samples, and its genome was recently sequenced.
Bioinformatic analysis of the R. champanellensis genome revealed numerous cohesin
and dockerin modules, the basic elements of the cellulosome, and manual
sequencing of partially sequenced genomic segments revealed two large tandem
scaffoldin-coding genes that form part of a gene cluster. Representative R.
champanellensis dockerins were tested against putative cohesins, and the results
revealed three different cohesin-dockerin binding profiles which implied two
major types of cellulosome architectures: (i) an intricate cell-bound system and
(ii) a simplistic cell-free system composed of a single cohesin-containing
scaffoldin. The cell-bound system can adopt various enzymatic architectures,
ranging from a single enzyme to a large enzymatic complex comprising up to 11
enzymes. The variety of cellulosomal components together with adaptor proteins
may infer a very tight regulation of its components. The cellulosome system of
the human gut bacterium R. champanellensis closely resembles that of the bovine
rumen bacterium Ruminococcus flavefaciens. The two species contain orthologous
gene clusters comprising fundamental components of cellulosome architecture.
Since R. champanellensis is the only human colonic bacterium known to degrade
crystalline cellulose, it may thus represent a keystone species in the human gut.
PMID- 25845889
TI - No DDRama at chromosome ends: TRF2 takes centre stage.
AB - Telomeres are nucleoprotein structures capping the natural termini of eukaryotic
linear chromosomes. Telomeres possess an inherent ability to circumvent the
activation of a full-blown DNA damage response (DDR), and hence fusion reactions,
by limiting inappropriate double-strand break (DSB) repair and processing
activities at eukaryotic chromosome ends. A telomere-specific protein complex,
termed shelterin, has a crucial function in safeguarding and securing telomere
integrity. Within this complex, TRF2 has emerged as the key player, dictating
different states of telomere protection during the replicative lifespan of a
cell. How TRF2 prevents activation of DSB repair activities at functional
telomeres has now been extensively investigated. In this review we aim at
exploring the complex and multi-faceted mechanisms underlying the TRF2-mediated
protection of eukaryotic chromosome ends.
PMID- 25845890
TI - Second Opinion: Does This Patient Really Have Narcolepsy?
PMID- 25845892
TI - OSA in Psychiatric Patients: Insomnia as a Concurrent Presentation of Autonomic
Dysregulation in OSA.
PMID- 25845891
TI - Chronotype and Improved Sleep Efficiency Independently Predict Depressive Symptom
Reduction after Group Cognitive Behavioral Therapy for Insomnia.
AB - STUDY OBJECTIVES: Cognitive behavioral therapy for insomnia (CBT-I) has been
shown to improve both sleep and depressive symptoms, but predictors of depression
outcome following CBT-I have not been well examined. This study investigated how
chronotype (i.e., morningness-eveningness trait) and changes in sleep efficiency
(SE) were related to changes in depressive symptoms among recipients of CBT-I.
METHODS: Included were 419 adult insomnia outpatients from a sleep disorders
clinic (43.20% males, age mean +/- standard deviation = 48.14 +/- 14.02). All
participants completed the Composite Scale of Morningness and attended at least 4
sessions of a 6-session group CBT-I. SE was extracted from sleep diary;
depressive symptoms were assessed using the Beck Depression Inventory (BDI) prior
to (Baseline), and at the end (End) of intervention. RESULTS: Multilevel
structural equation modeling revealed that from Baseline to End, SE increased and
BDI decreased significantly. Controlling for age, sex, BDI, and SE at Baseline,
stronger evening chronotype and less improvement in SE significantly and uniquely
predicted less reduction in BDI from Baseline to End. Chronotype did not predict
improvement in SE. CONCLUSIONS: In an insomnia outpatient sample, SE and
depressive symptoms improved significantly after a CBT-I group intervention. All
chronotypes benefited from sleep improvement, but those with greater eveningness
and/or less sleep improvement experienced less reduction in depressive symptom
severity. This suggests that evening preference and insomnia symptoms may have
distinct relationships with mood, raising the possibility that the effect of CBT
I on depressive symptoms could be enhanced by assessing and addressing circadian
factors.
PMID- 25845893
TI - Does surgery for obstructive sleep apnea provide value?
PMID- 25845894
TI - And the patient said: "let me be able to breathe and dream".
PMID- 25845895
TI - Caffeine Awareness in Children: Insights from a Pilot Study.
AB - STUDY OBJECTIVES: Caffeine, a commonly consumed psychoactive substance, can have
significant effects on sleep. Caffeine intake among children is increasing,
mainly in the form of sodas. However, adolescent caffeine consumers may lack
knowledge about the caffeine content in common beverages. If true, this very fact
may hamper the assessment of the effects of caffeine consumption on sleep in
children if such assessments are a priori dependent on responders being able to
reliably distinguish between caffeinated and noncaffeinated beverages. This
preliminary study investigated adolescents' caffeine knowledge and intake at a
Cleveland-area public middle school. METHODS: Seventh- and eighth-grade students
were surveyed using: (1) the Caffeine Literacy and Sleep Study (CLASS), a 15
question pilot instrument designed to assess caffeine knowledge and intake by
type, quantity and timing, as well as sleep habits; and (2) the Cleveland
Adolescent Sleepiness Questionnaire (CASQ), a validated survey measuring
excessive daytime sleepiness in adolescents. These questionnaires were
distributed and collected during a specified class period. RESULTS: Of the 635
seventh- and eighth-grade students who attended school on the day of the study,
555 (87%) participated. Lack of knowledge about caffeine content of particular
drinks was noted in seventh and eighth graders of both sexes with nearly 29%
unaware that their favorite drinks contain caffeine and more than 50% unable to
correctly identify the drinks with the most caffeine. A low percentage of
students correctly identified light-colored sodas lacking caffeine: 7-Up (24.1%),
Sierra Mist (38.9%), ginger ale (39.8%), Sprite (39.8%), and Fresca (53.7%). The
percentages of students correctly identifying caffeinated light-colored beverages
were: Arizona Green Tea (43.5%), Mello Yellow (50.9%), and A&W cream soda
(67.6%). However, Mountain Dew was correctly identified by most (93.5%) as
caffeinated. CONCLUSIONS: Students were not consistently able to identify
caffeine content or lack thereof in some common beverages. The results of this
pilot study show that caffeine literacy in adolescents warrants further
investigation and educational intervention.
PMID- 25845896
TI - Among Metabolic Factors, Significance of Fasting and Postprandial Increases in
Acyl and Desacyl Ghrelin and the Acyl/Desacyl Ratio in Obstructive Sleep Apnea
before and after Treatment.
AB - STUDY OBJECTIVES: There are reports suggesting that obstructive sleep apnea (OSA)
may itself cause weight gain. However, recent reports showed increases in body
mass index (BMI) following continuous positive airway pressure (CPAP) treatments.
When considering weight changes, changes in humoral factors that have significant
effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin,
and glucose and their interactions, examples of which are AG/DAG and AG/insulin,
are important. The aim of this study was to test the hypothesis that some
appetite-related factors had a specific profile before and after CPAP treatment.
METHODS: Metabolic parameters were measured cross-sectionally while fasting and
30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea
index < 15, n = 15) and moderate-to-severe OSA (apnea-hypopnea index >= 15, n =
39) participants in a single institute. There were no differences in age, sex,
BMI, or visceral fat accumulation between the two groups. Twenty-one patients
with moderate-to-severe OSA who received CPAP treatment also prospectively
underwent the same testing following 3 months of CPAP treatment. RESULTS:
Although fasting and postprandial glucose, insulin, and leptin levels did not
differ between no or mild OSA and moderate-to-severe OSA participants, AG and
DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions
were significantly increased in the moderate-to-severe OSA patients (p < 0.01).
After 3 months of CPAP treatment in 21 of the moderate-to-severe OSA
participants, AG/DAG did not change significantly, but other ghrelin-related
parameters including AG/insulin significantly decreased compared with values
before treatment but remained higher than in no or mild OSA. CONCLUSION: Among
several important metabolic factors, ghrelin-related factors had the strongest
associations with moderate-to-severe OSA. These results indicate that continuous
changes in ghrelin secretion in OSA patients existed at least within 3 months of
CPAP treatment. Methods to prevent OSA as well as treatment in its early stage
may be recommended.
PMID- 25845897
TI - Oral Appliance Treatment Response and Polysomnographic Phenotypes of Obstructive
Sleep Apnea.
AB - STUDY OBJECTIVES: Mandibular advancement splints (MAS) are an effective treatment
for obstructive sleep apnea (OSA); however, therapeutic response is variable.
Younger age, female gender, less obesity, and milder and supine-dependent OSA
have variably been associated with treatment success in relatively small samples.
Our objective was to utilize a large cohort of MAS treated patients (1) to
compare efficacy across patients with different phenotypes of OSA and (2) to
assess demographic, anthropometric, and polysomnography variables as treatment
response predictors. METHODS: Retrospective analysis of MAS-treated patients
participating in clinical trials in sleep centers in Sydney, Australia between
years 2000-2013. All studies used equivalent customized two-piece MAS devices and
treatment protocols. Treatment response was defined as (1) apnea-hypopnea index
(AHI) < 5/h, (2) AHI < 10/h and >= 50% reduction, and (3) >= 50% AHI reduction.
RESULTS: A total of 425 patients (109 female) were included (age 51.2 +/- 10.9
years, BMI 29.2 +/- 5.0 kg/m2). MAS reduced AHI by 50.3% +/- 50.7% across the
group. Supine-predominant OSA patients had lower treatment response rates than
non-positional OSA (e.g., 36% vs. 59% for AHI < 10/h). REM-predominant OSA showed
a lower response rate than either NREM or non-stage dependent OSA. In prediction
modelling, age, baseline AHI, and anthropometric variables were predictive of MAS
treatment outcome but not OSA phenotype. Gender was not associated with treatment
outcome. CONCLUSION: Lower MAS treatment response rates were observed in supine
and REM sleep. In a large sample, we confirm that demographic, anthropometric,
and polysomnographic data only weakly inform about MAS efficacy, supporting the
need for alternative objective prediction methods to reliably select patients for
MAS treatment.
PMID- 25845898
TI - Nightmares: Under-Reported, Undetected, and Therefore Untreated.
AB - OBJECTIVE: Nightmares are a robust and modifiable predictor of increased
suicidality and poor psychiatric outcomes, yet nightmare screening and treatment
remain rare, even in sleep centers. This paper aims to examine what proportion of
nightmare sufferers have discussed nightmares with a healthcare provider, as well
as possible explanations for low rates of nightmare complaints. METHODS: The
present study utilized a large United States community sample recruited through
mTurk and a student sample recruited from a large public university in the
Southeast United States. In Study 1, participants (n = 809) were asked whether
they had discussed nightmares with a healthcare provider. In Study 2 participants
(n = 747) were asked whether they believed nightmares were treatable in addition
to whether or not they had discussed nightmares with a healthcare provider.
RESULTS: Of the participants in Study 1 experiencing clinically significant
nightmare symptoms only 37.8% of participants reported discussing their
nightmares with a healthcare professional. In Study 2 only 11.1% of participants
with significant nightmares reporting having told a healthcare provider about
their nightmares. Further, of these individuals with clinically significant
nightmare symptoms, less than one-third believed that nightmares were treatable.
Higher nightmare severity was associated with a greater likelihood of reporting
nightmares to a healthcare physician as well as with lower beliefs that
nightmares are treatable. CONCLUSIONS: Our findings suggest that nightmares are
rarely reported to healthcare providers, which may explain the underutilization
of nightmare treatments. Given the poor outcomes associated with nightmares,
nightmare screening is warranted.
PMID- 25845899
TI - A 27-Year-Old Female on Chronic Opioid Therapy.
PMID- 25845901
TI - Nonrapid Eye Movement-Predominant Obstructive Sleep Apnea: Detection and
Mechanism.
AB - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) can be severe and present in
higher numbers during rapid eye movement (REM) than nonrapid eye movement (NREM)
sleep; however, OSA occurs in NREM sleep and can be predominant. In general,
ventilation decreases an average 10% to 15% during transition from wakefulness to
sleep, and there is variability in just how much ventilation decreases. As
dynamic changes in ventilation contribute to irregular breathing and breathing
during NREM sleep is mainly under chemical control, our hypothesis is that
patients with a more pronounced reduction in ventilation during the transition
from wakefulness to NREM sleep will have NREM- predominant rather than REM
predominant OSA. METHODS: A retrospective analysis of 451 consecutive patients
(apnea-hypopnea index [AHI] > 5) undergoing diagnostic polysomnography was
performed, and breath-to-breath analysis of the respiratory cycle duration, tidal
volume, and estimated minute ventilation before and after sleep onset were
examined. Values were calculated using respiratory inductance plethysmography.
The correlation between the percent change in estimated minute ventilation during
wake-sleep transitions and the percentage of apnea-hypopneas in NREM sleep (%AHI
in NREM; defined as (AHI-NREM) / [(AHI-NREM) + (AHI-REM)] * 100) was the primary
outcome. RESULTS: The decrease in estimated minute ventilation during wake-sleep
transitions was 15.0 +/- 16.6% (mean +/- standard deviation), due to a decrease
in relative tidal volume. This decrease in estimated minute ventilation was
significantly correlated with %AHI in NREM (r = -0.222, p < 0.01). CONCLUSIONS: A
greater dynamic reduction in ventilation back and forth from wakefulness to sleep
contributes to the NREM predominant OSA phenotype via induced ventilatory
instability.
PMID- 25845900
TI - Obstructive Sleep Apnea and Kidney Disease: A Potential Bidirectional
Relationship?
AB - Chronic kidney disease (CKD) is associated with high mortality rates and heavy
economic and social burdens. Nearly 10% of the United States population suffer
from CKD, with fatal outcomes increased by 16-40 times even before reaching end
stage renal disease. The prevalence of obstructive sleep apnea (OSA) is between
3% and 7% in the general population, and has increased dramatically during the
last 2 decades along with increased rates of obesity. However, the prevalence of
OSA is much greater in patients with CKD. In addition, aggressive dialysis
improves OSA. The current literature suggests a bidirectional association between
CKD and OSA through a number of potential pathological mechanisms, which increase
the possibility of both diseases being possible risk factors for each other. CKD
may lead to OSA through a variety of mechanisms, including alterations in
chemoreflex responsiveness, pharyngeal narrowing due to fluid overload, and
accumulation of uremic toxins. It is also being increasingly recognized that OSA
can also accelerate loss of kidney function. Moreover, animals exposed to
intermittent hypoxia suffer histopathological renal damage. Potential mechanisms
of OSA-associated renal dysfunction include renal hypoxia, hypertension,
endothelial dysfunction, activation of the sympathetic nervous system, and
increased oxidative stress.
PMID- 25845902
TI - Psychometric Properties of the Pittsburgh Sleep Quality Index (PSQI) in a Cohort
of Peruvian Pregnant Women.
AB - STUDY OBJECTIVES: We sought to evaluate the construct validity and factor
structure of the Spanish-language version of the Pittsburgh Sleep Quality Index
(PSQI) among pregnant Peruvian women. METHODS: A cohort of 642 women were
interviewed at <= 16 weeks of gestation. During interview, we ascertained
information about lifestyles, demographics, sleep characteristics, and mood
symptoms. Stress induced sleep disturbance, depressive symptoms, and anxiety
symptoms were evaluated using the Ford Insomnia Response to Stress Test (FIRST),
Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD
7) assessment scales, respectively. Consistency indices, exploratory and
confirmatory factor analyses, correlations, and logistic regressions were used.
RESULTS: Both exploratory and confirmatory factor analyses indicated a three
factor solution: sleep quality, sleep efficiency, and sleep medication. We
observed significantly positive correlations of the PSQI with the FIRST (0.42),
the PHQ-9 (0.49), and the GAD-7 (0.46). Poor sleepers (PSQI global score > 5) had
significantly increased odds of experiencing stress-induced sleep disturbance
(odds ratio, OR = 3.57; 95% CI: 2.40, 5.31), depression (OR = 5.48; 95% CI: 3.58,
8.37), and generalized anxiety disorder (OR = 4.57; 95% CI: 3.08, 6.76).
CONCLUSION: The Spanish-language version of the PSQI instrument was found to have
good construct validity among pregnant Peruvian women. Consistent with some other
studies, the PSQI was found to have a three-factor structure. Further assessment
and validation studies are needed to determine whether the three, factor-specific
scoring of the PSQI is favored over the PSQI global score in diverse populations.
PMID- 25845903
TI - The effect of physician continuing medical education on patient-reported outcomes
for identifying and optimally managing obstructive sleep apnea.
AB - STUDY OBJECTIVE: To evaluate the effect of continuing medical education (CME)
activities on patient reported outcomes with regard to (1) screening for
excessive sleepiness (ES) and obstructive sleep apnea (OSA) and (2) appropriate
referral and treatment. METHODS: A total of 725 patients were recruited from 75
providers who either participated or did not participate in Transtheoretical
Model (TTM)-based OSA CME activities. Patient reported outcomes from
participating (n = 36) and non-participating providers (n = 39) were compared
using generalized estimating equations examining random effects of provider as
unit of assignment. RESULTS: Patients' reports demonstrate that participating
physicians were 1.7 times more likely to initiate discussion of sleep problems
than non-participating physicians (t1,411 = 3.71, p = 0.05) and 2.25-2.86 times
more likely to administer validated measures for OSA (Epworth Sleepiness Scale
and STOP-BANG). Patient reports also indicated that participating clinicians
(79.9%) were significantly more likely to recommend seeing a sleep specialist
compared to non-participating clinicians (60.7%; t1,348 = 9.1, p < 0.01, OR =
2.6). Furthermore, while 89.4% of participating clinicians recommended a sleep
study, only 73.2% of the non-participating physicians recommended one (t1,363 =
11.46, p < 0.001, OR = 3.1). CONCLUSIONS: Participation in TTM-based OSA CME
activities was associated with improved patient reported outcomes compared to the
non-participating clinicians.
PMID- 25845904
TI - STAR syndrome is part of the differential diagnosis of females with anorectal
malformations.
PMID- 25845905
TI - Product stability and sequestration mechanisms in Solanum tuberosum engineered to
biosynthesize high value ketocarotenoids.
AB - To produce commercially valuable ketocarotenoids in Solanum tuberosum, the 4, 4'
beta-oxygenase (crtW) and 3, 3' beta-hydroxylase (crtZ) genes from Brevundimonas
spp. have been expressed in the plant host under constitutive transcriptional
control. The CRTW and CRTZ enzymes are capable of modifying endogenous plant
carotenoids to form a range of hydroxylated and ketolated derivatives. The host
(cv. Desiree) produced significant levels of nonendogenous carotenoid products in
all tissues, but at the apparent expense of the economically critical metabolite,
starch. Carotenoid levels increased in both wild-type and transgenic tubers
following cold storage; however, stability during heat processing varied between
compounds. Subcellular fractionation of leaf tissues revealed the presence of
ketocarotenoids in thylakoid membranes, but not predominantly in the
photosynthetic complexes. A dramatic increase in the carotenoid content of
plastoglobuli was determined. These findings were corroborated by microscopic
analysis of chloroplasts. In tuber tissues, esterified carotenoids, representing
13% of the total pigment found in wild-type extracts, were sequestered in
plastoglobuli. In the transgenic tubers, this proportion increased to 45%, with
esterified nonendogenous carotenoids in place of endogenous compounds.
Conversely, nonesterified carotenoids in both wild-type and transgenic tuber
tissues were associated with amyloplast membranes and starch granules.
PMID- 25845906
TI - National Institutes of Health Stroke Scale score is an unreliable predictor of
perfusion deficits in acute stroke.
AB - BACKGROUND: Perfusion-weighted magnetic resonance imaging is not routinely used
to investigate stroke/transient ischemic attack. Many clinicians use perfusion
weighted magnetic resonance imaging selectively in patients with more severe
neurological deficits, but optimal selection criteria have never been identified.
AIMS AND/OR HYPOTHESIS: We tested the hypothesis that a National Institutes of
Health Stroke Scale score threshold can be used to predict the presence of
perfusion-weighted magnetic resonance imaging deficits in patients with acute
ischemic stroke/transient ischemic attack. METHODS: National Institutes of Health
Stroke Scale scores were prospectively assessed in 131 acute stroke/transient
ischemic attack patients followed by magnetic resonance imaging, including
perfusion-weighted magnetic resonance imaging within 72 h of symptom onset.
Patients were dichotomized based on the presence or absence of perfusion deficits
using a threshold of Tmax (time to peak maps after the impulse response) delay
>=four-seconds and a hypoperfused tissue volume of >=1 ml. RESULTS: Patients with
perfusion deficits (77/131, 59%) had higher median (interquartile range) National
Institutes of Health Stroke Scale scores (8 [12]) than those without perfusion
deficits (3 [4], P < 0.001). A receiver operator characteristic analysis
indicated poor to moderate sensitivity of National Institutes of Health Stroke
Scale scores for predicting perfusion deficits (area under the curve = 0.787). A
National Institutes of Health Stroke Scale score of >=6 was associated with
specificity of 85%, but sensitivity of only 69%. No National Institutes of Health
Stroke Scale score threshold identified all cases of perfusion-weighted magnetic
resonance imaging deficits with sensitivity >94%. CONCLUSIONS: Although higher
National Institutes of Health Stroke Scale scores are predictive of perfusion
deficits, many patients with no clinically detectable signs have persisting
cerebral blood flow changes. A National Institutes of Health Stroke Scale score
threshold should therefore not be used to select patients for perfusion-weighted
magnetic resonance imaging. Perfusion-weighted magnetic resonance imaging should
be considered in all patients presenting with acute focal neurological deficits,
even if these deficits are transient.
PMID- 25845907
TI - Can Dynamic Spectral Imaging System colposcopy replace conventional colposcopy in
the detection of high-grade cervical lesions?
AB - The sensitivity of conventional colposcopy for the detection of high-grade
cervical lesions (cervical intraepithelial neoplasia stage 2 or above; CIN2+) is
poor. We aimed to investigate if a Dynamic Spectral Imaging System (DySIS) can
enhance or replace conventional colposcopy in clinical practice. From 3 December
2013 to 29 January 2014 a total of 239 women were included. All women were
referred to the Department of Obstetrics and Gynecology, Aarhus, Denmark because
of an abnormal cytology result. Every woman had three to five cervical punch
biopsies taken; two biopsies were taken following DySIS recommendations.
Subsequent biopsies were taken following the clinician's assessment or randomly.
DySIS allowed detection of five CIN2+ cases (7.4%) that would not have been
detected otherwise, but it failed to detect 46 of CIN2+ cases (67.6%). The
sensitivity and specificity of DySIS for detecting CIN2+ was 32.4 and 83.0%,
respectively. DySIS colposcopy seemed inferior to conventional colposcopy in
detecting high-grade lesions and cannot replace conventional colposcopy with
random biopsies.
PMID- 25845908
TI - Characteristics of caring self-efficacy in pediatric nurses: a qualitative study.
AB - PURPOSE: The present study was conducted to clarify pediatric nurses'
characteristics of caring self-efficacy. DESIGN AND METHODS: This study was
conducted using a qualitative content analysis approach. The participants
included 27 pediatric nurses and clinical instructors, selected purposively. Data
were collected using semi-structured interviews and were analyzed using the
content analysis method. RESULTS: Data analysis generated four main themes as
attributes of a self-efficient pediatric nurse including: (a) professional
communications; (b) management of care; (c) altruism; and (d) proficiency.
PRACTICE IMPLICATIONS: Nursing managers and instructors can use these results to
help develop nurses' empowerment and self-efficacy, especially in pediatric care.
PMID- 25845909
TI - Universality of Oxime K203 for Reactivation of Nerve Agent-Inhibited AChE.
AB - Oxime K203 seems to be the most promising oxime in case of reactivation of tabun
inhibited acetylcholinesterase (AChE). Although it was originally developed for
treatment of tabun intoxications, it is able to reactivate cholinesterases
inhibited by other nerve agents. This study is aimed at the evaluation of its
potency in vitro against other nerve agents. For this purpose, sarin, tabun,
cyclosarin, soman, VX, Russian VX and DFP were selected as members of the nerve
agent family to check its universality. At high concentrations (10(-3) M), oxime
K203 reached promising reactivation activity. At low concentrations, relevant for
human use (10(-5) M), promising reactivation potency was obtained only with
tabun. In conclusion, oxime K203 reactivates other nerve agents-inhibited
cholinesterases, however its broad-spectrum reactivation is limited at high, for
human not attainable, concentrations only.
PMID- 25845910
TI - Analysis of gene expression profiles associated with glioma progression.
AB - The present study aimed to investigate changes at the transcript level that are
associated with spontaneous astrocytoma progression, and further, to discover
novel targets for glioma diagnosis and therapy. GSE4290 microarray data
downloaded from Gene Expression Omnibus were used to identify the differentially
expressed genes (DGEs) by significant analysis of microarray (SAM). The Short
Time Series Expression Miner (STEM) method was then applied to class these DEGs
based on their degrees of differentiation in the process of tumor progression.
Finally, EnrichNet was used to perform the Kyoto Encyclopedia of Genes and
Genomes (KEGG) pathway enrichment analysis based on a protein-protein interaction
(PPI) network. A total of 4,506 DEGs were detected, and the number of DEGs was
the highest in grade IV cells (2,580 DEGs). These DEGs were classified into nine
clusters by the STEM method. In total, 11 KEGG pathways with XD-scores larger
than the threshold (0.96) were obtained. The DEGs enriched in pathways 1
(extracellular matrix-receptor interaction), 3 (phagosome) and 6 (type I diabetes
mellitus) mainly belonged to cluster 5. Pathway 2 (long-term potentiation), 4
(Vibrio cholerae infection) and 5 (epithelial cell signaling in Helicobacter
pylori infection) was involved with DEGs that belonged to different clusters.
Significant changes in gene expression occurred during glioma progression.
Pathways 1, 3 and 6 may be important for the deterioration of glioma into
glioblastoma, and pathways 2, 4 and 5 may have a role at each stage during glioma
progression. The associated DEGs, including SV2, NMDAR and mGluRs, may be
suitable as biomarkers or therapeutic targets for gliomas.
PMID- 25845912
TI - "Toothbrush" the Feet: A Periodic Mechanical Stimulus for Healing of a Severe
Chronic Leg Ulcer.
AB - Chronic wounds develop when the sequence of healing events are disrupted, usually
in patients with underlying diseases such as diabetes mellitus, venous
insufficiency, peripheral artery disease, and neuropathies and they affect most
often the lower extremities. We present a 68-year-old woman with plantar
ulceration, lasting for approximately 18 months, resistant to healing with
conventional therapy and various modalities we used. The patient had a long
history of seronegative enteropathic arthritis, Crohn's disease, secondary
fibrillar amyloidosis, multiplex neuropathy, and small vessel vasculitis, the
latter being the trigger event for the ulceration of her right foot. Before the
decision for a final surgical intervention, we implemented a mechanical periodic
stimulus using a soft toothbrush, which resulted in the gradual and complete
healing of the ulcer within a period of 6 weeks. Patient's history and previous
treatments are presented along with the procedures that led to the healing of the
chronic wound. This report supports the idea that periodic mechanical stimulus is
of great importance for the healing process and this could be the mechanism of
action of some other methods that have been described in the medical literature.
PMID- 25845911
TI - Remission of systemic lupus erythematosus disease activity with regulatory
cytokine interleukin (IL)-35 in Murphy Roths Large (MRL)/lpr mice.
AB - The immunological mechanisms mediated by regulatory cytokine interleukin (IL)-35
are unclear in systemic lupus erythematosus (SLE). We investigated the frequency
of CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) regulatory T (Treg ) and IL
10(+) regulatory B (Breg ) cells and related immunoregulatory mechanisms in a
female Murphy Roths Large (MRL)/lpr mouse model of spontaneous lupus-like
disease, with or without IL-35 treatment. A remission of histopathology
characteristics of lupus flare and nephritis was observed in the MRL/lpr mice
upon IL-35 treatment. Accordingly, IL-35 and IL-35 receptor subunits (gp130 and
IL-12Rbeta2) and cytokines of MRL/lpr and BALB/c mice (normal controls) were
measured. The increased anti-inflammatory cytokines and decreased proinflammatory
cytokines were possibly associated with the restoration of Treg and Breg
frequency in MRL/lpr mice with IL-35 treatment, compared to phosphate-buffered
saline (PBS) treatment. mRNA expressions of Treg -related FoxP3, IL-35 subunit
(p35 and EBI3) and soluble IL-35 receptor subunit (gp130 and IL12Rbeta2) in
splenic cells were up-regulated significantly in IL-35-treated mice. Compared
with the PBS treatment group, IL-35-treated MRL/lpr mice showed an up-regulation
of Treg -related genes and the activation of IL-35-related intracellular Janus
kinase/signal transducer and activator of transcription signal pathways, thereby
indicating the immunoregulatory role of IL-35 in SLE. These in vivo findings may
provide a biochemical basis for further investigation of the regulatory
mechanisms of IL-35 for the treatment of autoimmune-mediated inflammation.
PMID- 25845913
TI - What is the right timing for ultrasound evaluation after pregnancy termination
with mifepristone?
AB - OBJECTIVE: To determine the timing for ultrasound evaluation after medical
termination of pregnancy (MTOP). STUDY DESIGN: The records of 301 consecutive
women who underwent MTOP between July 2010 and July 2011 were studied
retrospectively. The follow-up protocol included ultrasound evaluation 2 weeks
after MTOP. Surgical termination was offered when pregnancy was found to be
ongoing, and either hysteroscopy/curettage or a repeat ultrasound 2 weeks later
was offered when the ultrasound findings were suspicious for retained products of
conception. Pathology reports were used to confirm the presence of retained
products of conception. RESULTS: Women with ultrasound findings suspicious for
retained products of conception were significantly older than women with negative
ultrasound findings (30.9+/-7.7 years vs 24.8+/-6 years, p<0.0001). Two weeks
after MTOP, ultrasound findings were negative in 236 women and suspicious in 66
women. This rate declined as the interval between ultrasound evaluation and MTOP
increased (up to 10 weeks). Of the 18 women (5.98%) who underwent
hysteroscopy/curettage, pathology reports indicated that 15 (83.3%) had true
residua. CONCLUSIONS: At 2 weeks after MTOP, ultrasound findings suspicious for
retained products of conception do not conclusively indicate failure of the
procedure. Ultrasound evaluation should be repeated 4-6 weeks later (6-8 weeks
after MTOP) in women with suspected residua before diagnosing failure of the
procedure.
PMID- 25845914
TI - Antidepressants during pregnancy and postpartum hemorrhage: a systematic review.
AB - The use of antidepressants in pregnancy is increasing. Concerns have risen about
the use of antidepressants during pregnancy and the risk of postpartum hemorrhage
(PPH). The aim of this systematic review is to summarize evidence on the
association between use of antidepressants during pregnancy and the risk of PPH.
An Embase and Pubmed search was conducted. English and Dutch language studies
reporting original data regarding bleeding after delivery associated with
exposure to antidepressants during pregnancy were selected. Quality appraisal was
conducted using the Newcastle Ottawa Scale (NOS). Out of 81 citations, 4 studies
were included. Based on the NOS, 3 were considered of good quality and 1 was
considered of satisfactory quality. Two studies reported an increased incidence
of PPH in women who used antidepressants during pregnancy. The other two studies
identified no overall increased risk of PPH among pregnant women exposed to
antidepressants. The existing evidence remains inconclusive whether use of
antidepressants during pregnancy is associated with an increased risk of
postpartum hemorrhage. If there is such an association the absolute increased
risk will be low and the clinical relevance needs to be further examined.
PMID- 25845915
TI - Development of the nasolacrimal apparatus in the Mongolian gerbil (Meriones
unguiculatus), with notes on network topology and function.
AB - The nasolacrimal apparatus (NLA) is a multicomponent functional system comprised
of multiple orbital glands (up to four larger multicellular exocrine structures),
a nasal chemosensory structure (vomeronasal organ: VNO), and a connecting duct
(nasolacrimal duct: NLD). Although this system has been described in all tetrapod
vertebrate lineages, albeit not always with all three main components present,
considerably less is known about its ontogeny. The Mongolian gerbil (Meriones
unguiculatus) is a common lab rodent in which the individual components of the
adult NLA have been well studied, but as yet nothing is known about the ontogeny
of the NLA. In this study, serial sections of 15 fetal and three adult Mongolian
gerbil heads show that the development of the NLA falls into three fetal stages:
inception (origin of all features), elongation (lengthening of all features), and
expansion (widening of all features). No postnatal or juvenile specimens were
observed in this study, but considerable growth evidently occurs before the final
adult condition is reached. The development of the orbital glands and the VNO in
the Mongolian gerbil is largely consistent with those in other mammals, despite a
slight nomenclatural conundrum for the anterior orbital glands. However, the
Mongolian gerbil NLD follows a more circuitous route than in other tetrapods, due
mainly to the convoluted arrangement of the narial cartilages, the development of
a pair of enlarged incisors as well as an enlarged infraorbital foramen. The
impact of these associated features on the ontogeny and phylogeny of the NLA
could be examined through the approach of network science. This approach allows
for the incorporation of adaptations to specific lifestyles as potential
explanations for the variation observed in the NLA across different tetrapod
clades.
PMID- 25845916
TI - How reliable are field-derived biomagnification factors and trophic magnification
factors as indicators of bioaccumulation potential? Conclusions from a case study
on per- and polyfluoroalkyl substances.
AB - This review examines the usefulness of the metrics BMF (biomagnification factor)
and TMF (trophic magnification factor), derived from field measurements of the
levels of contaminants in naturally occurring biota, for characterizing the
bioaccumulation potential ("B") of chemicals. Trophic magnification factor and
BMF values greater than 1.0 are often considered to be the most conclusive
indicators of B status, and the TMF criterion has been referred to as the "gold
standard" for B categorization. Although not wishing to dispute the theoretical
primacy of field-derived BMFs and TMFs as B metrics, we make the case that, in
practice, the study-to-study (and even within-study) variability of the results
is so great that they are of very restricted usefulness for assessing B status,
at least in the case of the per- and polyfluoroalkyl substances (PFASs), on which
we focus here. This conclusion is based on an analysis of the results of 24 peer
reviewed studies reporting field-derived BMFs or TMFs for 14 PFASs, for which BMF
values often range over several orders of magnitude from <<1.0 to >>1.0,
sometimes even in the same study. For TMFs, the range is a factor of
approximately 20 for the most intensely studied PFASs (perfluorooctanoic acid
[PFOA] and perfluorooctanesulfonic acid [PFOS]). We analyze the possible causes
for such variability: To some extent it results from the differing ways in which
the metrics are expressed, but most of the scatter is likely attributable to such
factors as nonachievement of the tacitly assumed steady-state conditions,
uncertainties in the feeding ecology, the impact of metabolism of precursor
compounds, and so forth. As more trustworthy alternatives to field-derived BMFs
and TMFs, we suggest the implementation of dietary BMF studies performed under
strictly controlled conditions on aquatic, terrestrial, and avian species, as
well as the consideration of measured elimination half-lives, which have been
demonstrated to be directly related to BMF values.
PMID- 25845917
TI - Health and Economic Outcomes Associated with Use of an Antimicrobial Envelope as
a Standard of Care for Cardiac Implantable Electronic Device Implantation.
AB - INTRODUCTION: Infection of cardiac implanted electrical devices (CIED) is a
problem. In selected patients, use of an "antibacterial envelope" (AIGISRx(r)) is
associated with low CIED infection rates. The value of this device when used as a
standard of care is unclear. METHODS AND RESULTS: Retrospective analysis of all
patients (N = 1,476) who underwent CIED implantation at a single hospital. During
the study period, some implanters used the AIGISRx as a standard of care (Yes
AIGISRx Group, N = 365), whereas others did not use it at all (No-AIGISRx Group,
N = 1,111). A risk score based on preoperative factors was calculated for each
patient. Rates of CIED infection within 6 months were measured, and associated
costs were estimated. The Yes-AIGISRx and No-AIGISRx groups had similar
preoperative infection risk. In the No-AIGISRx group, 19 infections were observed
(1.7%), versus 0 in the Yes-AIGISRx group (P = 0.006). The 6-month mortality rate
among patients with infection was significantly greater than among those without
infection (15.7% vs. 4.5%, P = 0.021). The average hospital duration for
infection care was 13 days. By extrapolating the infection rate and costs
observed in the No-AIGISRx group to the Yes-AIGISRx group, we estimated that
there would have been 6.2 additional infections costing approximately $340,000.
This cost was similar to the actual cost of the devices in the Yes-AIGISRx group,
estimated at $320,000. CONCLUSIONS: Standard of care use of an antibacterial
envelope as a standard of care was associated with a significantly lower rate of
CIED infection, and appeared to be economically reasonable. Prospective trials to
address these findings may be worthwhile.
PMID- 25845918
TI - Abdominal pain endpoints currently recommended by the FDA and EMA for adult
patients with irritable bowel syndrome may not be reliable in children.
AB - BACKGROUND: The Food and Drug Administration (FDA) recommended >=30% decrease on
patient-reported outcomes for pain be considered clinically significant in
clinical trials for adults with irritable bowel syndrome. This percent change
approach may not be appropriate for children. We compared three alternate
approaches to determining clinically significant reductions in pain among
children. METHODS: 80 children with functional abdominal pain participated in a
study of the efficacy of amitriptyline. Endpoints included patient-reported
estimates of feeling better, and pain Visual Analog Scale (VAS). The minimum
clinically important difference in pain report was calculated as (i) mean change
in VAS score for children reporting being 'better'; (ii) percent changes in pain
(>=30% and >=50%) on the VAS; and (iii) statistically reliable changes on the VAS
for 68% and 95% confidence intervals. KEY RESULTS: There was poor agreement
between the three approaches. 43.6% of the children who met the FDA >=30%
criterion for clinically significant change did not achieve a reliable level of
improvement (95% confidence interval). CONCLUSIONS & INFERENCES: Children's self
reported ratings of being better may not be statistically reliable. A combined
approach in which children must report improvement as better and achieve a
statistically significant change may be more appropriate for outcomes in clinical
trials.
PMID- 25845926
TI - Substrate Specificity Profiling of Peptidyl-Lys Metallopeptidase of Armillaria
mellea by FRET Based Peptide Library.
AB - Determining the substrate specificity of a protease is essential for developing
assays, inhibitors and understanding the mechanisms of the enzyme. In this work,
we have profiled the specificity of Peptidyl-Lys metallopeptidase, (LysN), of
Armillaria mellea, by a synthetic fluorescence resonance energy transfer (FRET)
positional-scanning library. The library was based on a reference sequence K(Abz)
S-A-Q-K-M-V-S-K(Dnp), where the fluorescent donor is 2-aminobenzamide and the
quencher is N-2,4-dinitrophenyl. Each position was varied between 19 different
amino acids one by one, to reveal the specificity of the protease. LysN exhibits
strict specificity for lysine in S1', and has less specificity moving further
away from the scissile bond. Additivity between the subsites was observed and the
best substrate identified was K(Abz)-M-R-F-K-R-R-R-K(Dnp) with a kcat/KM of 42.6
uM/s. Based on a homology structure model the reference substrate was fitted into
the active site using molecular dynamics to propose peptide-enzyme interactions.
PMID- 25845927
TI - Non-carbapenem therapy of urinary tract infections caused by extended-spectrum
beta-lactamase-producing Enterobacteriaceae.
AB - PURPOSE: We determined the prevalence of ESBL Enterobacteriaceae in urinary tract
infections among inpatients, identified risk factors of acquisition, and
evaluated the effectiveness of alternatives to carbapenems. METHODS: The
clinical, microbiological, and therapeutic data as well as the outcomes were
recorded for all ESBL-E positive urine samples for three months. RESULTS: Thirty
one (4%) of the 762 Enterobacteriaceae positive cultures were ESBL producers. The
predisposing conditions for being infected with those strains were:
immunodepression (61%), recent hospitalization (52%), recent antibiotic therapy
(52%), and urinary catheterization (61%). 19% of infections were community
acquired. The seven cases of acute pyelonephritis and five of prostatitis were
treated with piperacillin-tazobactam (5), fluoroquinolones (4), ceftazidime (2),
or carbapenems (only 1) after specialized advice. Four (33%) patients relapsed at
week 10: three were immunodepressed and three presented with bacteremia.
CONCLUSIONS: Alternatives to carbapenems (especially piperacillin-tazobactam)
seem to be a good option for non-bacteremic UTI in immunocompetent patients.
PMID- 25845928
TI - The current role of next-generation DNA sequencing in routine care of patients
with hereditary cardiovascular conditions: a viewpoint paper of the European
Society of Cardiology working group on myocardial and pericardial diseases and
members of the European Society of Human Genetics.
PMID- 25845929
TI - Neutrophil extracellular traps: a new source of tissue factor in
atherothrombosis.
PMID- 25845930
TI - Patient outcomes according to adherence to treatment guidelines for rhythm
control of atrial fibrillation.
AB - BACKGROUND: Although guidelines for antiarrhythmic drug therapy in atrial
fibrillation (AF) were published in 2006, it remains uncertain whether adherence
to these guidelines affects patient outcomes. METHODS AND RESULTS: We
retrospectively evaluated the records of 5976 consecutive AF patients who were
prescribed at least 1 antiarrhythmic drug between 2006 and 2013. Patients with 1
or more prescribed antiarrhythmic drugs that did not comply with guideline
recommendations comprised the non-guideline-directed group (=2920); the remainder
constituted the guideline-directed group (=3056). Time to events was assessed
using the survival analysis method and adjusted for covariates using Cox
regression. Rates of adherence to the guidelines increased significantly with a
higher degree of prescriber specialization in arrhythmias (49%, 55%, and 60% for
primary care physicians, general cardiologists, and cardiac electrophysiologists,
respectively, P=0.001) for the first prescribed antiarrhythmic drug. Compared to
the non-guideline-directed group, the guideline-directed group had higher rates
of heart failure, but lower baseline CHADS2-VASc scores (P<0.001) and lower rates
of coronary artery disease, valvular disease, hypertension, hyperlipidemia,
pulmonary disease, and renal insufficiency (P<0.05 for all). During 45 +/- 26
months follow-up, the guideline-directed group had a lower risk of AF recurrence
(hazard ratio=0.86, 95% CI=0.80 to 0.93), fewer hospital admissions for AF
(hazard ratio=0.87, 95% CI=0.79 to 0.97), and fewer procedures for recurrent AF,
including electrical cardioversion, pacemaker implantation, and atrioventricular
nodal ablation (P<0.01 for all). The mortality and stroke risks were similar
between the groups. CONCLUSIONS: Adherence to published guidelines in the
antiarrhythmic management of AF is associated with improved patient outcomes.
PMID- 25845932
TI - Current lipid-modifying agents.
PMID- 25845931
TI - Endogenously generated omega-3 fatty acids attenuate vascular inflammation and
neointimal hyperplasia by interaction with free fatty acid receptor 4 in mice.
AB - BACKGROUND: Omega-3 polyunsaturated fatty acids (omega3 PUFAs) suppress
inflammation through activation of free fatty acid receptor 4 (FFAR4), but this
pathway has not been explored in the context of cardiovascular disease. We aimed
to elucidate the involvement of FFAR4 activation by omega3 PUFAs in the process
of vascular inflammation and neointimal hyperplasia in mice. METHODS AND RESULTS:
We used mice with disruption of FFAR4 (Ffar4(-/-)), along with a strain that
synthesizes high levels of omega3 PUFAs (fat-1) and a group of crossed mice
(Ffar4(-/-)/fat-1), to elucidate the role of FFAR4 in vascular dysfunction using
acute and chronic thrombosis/vascular remodeling models. The presence of FFAR4 in
vascular-associated cells including perivascular adipocytes and macrophages, but
not platelets, was demonstrated. omega3 PUFAs endogenously generated in fat-1
mice (n=9), but not in compound Ffar4(-/-)/fat-1 mice (n=9), attenuated femoral
arterial thrombosis induced by FeCl3. Neointimal hyperplasia and vascular
inflammation in the common carotid artery were significantly curtailed 4 weeks
after FeCl3 injury in fat-1 mice (n=6). This included greater luminal diameter
and enhanced blood flow, reduced intima:media ratio, and diminished macrophage
infiltration in the vasculature and perivascular adipose tissue compared with
control mice. These effects were attenuated in the Ffar4(-/-)/fat-1 mice.
CONCLUSIONS: These results indicate that omega3 PUFAs mitigate vascular
inflammation, arterial thrombus formation, and neointimal hyperplasia by
interaction with FFAR4 in mice. Moreover, the omega3 PUFA-FFAR4 pathway decreases
inflammatory responses with dampened macrophage transmigration and infiltration.
PMID- 25845933
TI - Synthesis of trans-16-triazolyl-13alpha-methyl-17-estradiol diastereomers and the
effects of structural modifications on their in vitro antiproliferative
activities.
AB - Novel 16-triazoles in the 13alpha-estrone series were synthesized via Cu(I)
catalyzed azide-alkyne cycloaddition of the two diastereomeric (on C-16 and on C
17) 16-azido-13alpha-estra-1,3,5(10)-trien-17-ol 3-benzyl ethers with substituted
phenylacetylenes. The new heterocyclic derivatives were evaluated in vitro by
means of MTT assays for antiproliferative activity against a panel of human
adherent cancer cell lines (HeLa, MCF-7, A431, A2780, T47D, MDA-MB-231 and MDA-MB
361). The inversion of the configurations at C-16 and C-17 selectively affected
the growth-inhibitory properties of the tested compounds. The 16beta,17alpha
isomers generally proved to be potent on all cell lines, with IC50 values
comparable to those of the reference agent cisplatin. Change of the substitution
pattern of the phenyl group of the acetylene led to great differences in
antiproliferative properties. Exclusively the p-phenyl-substituted triazoles
exerted high cytostatic effects. One of the most potent compounds activated
caspase-3 and caspase-9 without influencing caspase-8, confirming the induction
of apoptosis via the intrinsic pathway.
PMID- 25845934
TI - A review of 1alpha,25(OH)2D3 dependent Pdia3 receptor complex components in Wnt5a
non-canonical pathway signaling.
AB - Wnt5a and 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] regulate endochondral
ossification. 1alpha,25(OH)2D3 initiates its calcium-dependent effects via its
membrane-associated receptor, protein disulfide isomerase A3 (Pdia3).
1alpha,25(OH)2D3 binding to Pdia3 triggers the interaction between Pdia3 and
phospholipase A2 (PLA2)-activating protein (PLAA), resulting in downstream
activation of calcium/calmodulin-dependent protein kinase II (CaMKII), PLA2, and
protein kinase C (PKC). Wnt5a initiates its calcium-dependent effects via binding
its receptors Frizzled2 (FZD2) and Frizzled5 (FZD5) and receptor tyrosine kinase
like orphan receptor 2 (ROR2), activating intracellular calcium release and
stimulating PKC and CaMKII. Recent efforts to determine the inter-relation
between Wnt5a and 1alpha,25(OH)2D3 signaling pathways have demonstrated that
Wnt5a signals through a CaMKII/PLA2/PGE2/PKC cascade in chondrocytes and
osteoblasts in which the components of the Pdia3 receptor complex were required.
Furthermore, ROR2, but not FZD2 or FZD5, was required to mediate the calcium
dependent actions of 1alpha,25(OH)2D3. This review provides evidence that
1alpha,25(OH)2D3 and Wnt5a mediate their calcium-dependent pathways via similar
receptor components and proposes that these pathways may interact since they are
competing for the same receptor complex components.
PMID- 25845935
TI - Heat waves imposed during early pod development in soybean (Glycine max) cause
significant yield loss despite a rapid recovery from oxidative stress.
AB - Heat waves already have a large impact on crops and are predicted to become more
intense and more frequent in the future. In this study, heat waves were imposed
on soybean using infrared heating technology in a fully open-air field
experiment. Five separate heat waves were applied to field-grown soybean (Glycine
max) in central Illinois, three in 2010 and two in 2011. Thirty years of
historical weather data from Illinois were analyzed to determine the length and
intensity of a regionally realistic heat wave resulting in experimental heat wave
treatments during which day and night canopy temperatures were elevated 6
degrees C above ambient for 3 days. Heat waves were applied during early or late
reproductive stages to determine whether and when heat waves had an impact on
carbon metabolism and seed yield. By the third day of each heat wave, net
photosynthesis (A), specific leaf weight (SLW), and leaf total nonstructural
carbohydrate concentration (TNC) were decreased, while leaf oxidative stress was
increased. However, A, SLW, TNC, and measures of oxidative stress were no
different than the control ca. 12 h after the heat waves ended, indicating rapid
physiological recovery from the high-temperature stress. That end of season seed
yield was reduced (~10%) only when heat waves were applied during early pod
developmental stages indicates the yield loss had more to do with direct impacts
of the heat waves on reproductive process than on photosynthesis. Soybean was
unable to mitigate yield loss after heat waves given during late reproductive
stages. This study shows that short high-temperature stress events that reduce
photosynthesis and increase oxidative stress resulted in significant losses to
soybean production in the Midwest, U.S. The study also suggests that to mitigate
heat wave-induced yield loss, soybean needs improved reproductive and
photosynthetic tolerance to high but increasingly common temperatures.
PMID- 25845937
TI - Protein-losing enteropathy cured by resection of adenomatous goiter: report of a
case.
AB - A 51-year-old Japanese woman presented to our hospital with systemic edema and
general fatigue. Her serum albumin level was very low (1.5 g/dL). Technetium-99 m
human serum albumin ((99m)Tc-HSA) scintigraphy showed albumin leakage from the
upper small bowel. Magnetic resonance lymphangiography showed dilated lymphatic
vessels in the chest, whereas double-balloon enteroscopy (DBE) showed white villi
and chyle leakage in the deeper part of the duodenal mucosa. A duodenal mucosa
biopsy specimen revealed lymphangiectasia. She was diagnosed with protein-losing
enteropathy (PLE). Treatment with a fat-restricted diet and tranexamic acid-
previously reported to be effective against PLE--was attempted, but was
ineffective. A thyroid tumor was simultaneously detected in her left neck, and
was found to extend to the mediastinum on computed tomography. The tumor (size,
>5 cm) was resected, and a pathological diagnosis of adenomatous goiter was made.
The patient's serum albumin level increased to normal levels within 1 month
postoperatively. After 6 months, (99m)Tc-HSA scintigraphy showed no albumin
leakage from the gastrointestinal tract, and disappearance of white villi and
chyle leakage on DBE. No lymphangiectasia was noted in the biopsy specimen.
Adenomatous goiter was thus considered the cause of the PLE, possibly through
lymph flow obstruction in the mediastinum.
PMID- 25845936
TI - Neuronally produced versican V2 renders C-fiber nociceptors IB4 -positive.
AB - A subpopulation of nociceptors, the glial cell line-derived neurotrophic factor
(GDNF)-dependent, non-peptidergic C-fibers, expresses a cell-surface
glycoconjugate that can be selectively labeled with isolectin B4 (IB4 ), a
homotetrameric plant lectin from Griffonia simplicifolia. We show that versican
is an IB4 -binding molecule in rat dorsal root ganglion neurons. Using reverse
transcriptase polymerase chain reaction (RT-PCR), in situ hybridization and
immunofluorescence experiments on rat lumbar dorsal root ganglion, we provide the
first demonstration that versican is produced by neurons. In addition, by probing
Western blots with splice variant-specific antibodies we show that the IB4
binding versican contains only the glycosaminoglycan alpha domain. Our data
support V2 as the versican isoform that renders this subpopulation of nociceptors
IB4 -positive (+). A subset of nociceptors, the GDNF-dependent non-peptidergic C
fibers can be characterized by its reactivity for isolectin B4 (IB4), a plant
lectin from Griffonia simplicifolia. We have previously demonstrated that
versican V2 binds IB4 in a Ca2 + -dependent manner. However, given that versican
is thought to be the product of glial cells, it was questionable whether versican
V2 can be accountable for the IB4-reactivity of this subset of nociceptors. The
results presented here prove - for the first time - a neuronal origin of versican
and suggest that versican V2 is the molecule that renders GDNF-dependent non
peptidergic C-fibers IB4-positive.
PMID- 25845938
TI - Stereocontrolled synthesis of vicinally functionalized piperidines by
nucleophilic beta-addition of alkyllithiums to alpha-aryl substituted piperidine
enecarbamates.
AB - Substituted piperidines are emerging as important medicinally-active structural
motifs. Here, we report highly stereoselective carbolithiation reactions of alpha
aryl piperidine enecarbamates that offer direct access to vicinally-substituted
piperidine compounds. We have also demonstrated that the carbanion intermediates
can be trapped with a carbon electrophile.
PMID- 25845939
TI - Prenatal Detection of Coarctation of the Aorta in a Non-selected Population: A
Prospective Analysis of 10 Years of Experience.
AB - The objective of this study was to assess the ability of different parameters to
identify fetuses requiring neonatal care for coarctation of the aorta (CoA).
Between January 2003 and December 2012, 175 fetuses referred for great vessel
disproportion were divided into two groups: group A (n = 51) with high risk of
CoA and delivery planned in tertiary care referral center and group B (n = 124)
with no increased risk of CoA. In group A, diagnosis of CoA was confirmed in
38/51 (74 %). In group B, 2/124 had CoA. Multiple logistic regression analysis
identified the best combination as diffusely hypoplastic and/or angular aortic
arches, ventricular septal defect and aortic valve diameter <5 mm at 36-week
gestational age (GA). Positive predictive value was 75 % when vessel
disproportion was noted before 28-week GA and 73 % in the third trimester.
Postnatal diagnosis involved 38 cases of CoA which had not been referred. One
case of CoA diagnosed after birth was referred prenatally for difficulty of
screening without any defect. The results of our prospective study are in
agreement with those of previous series, but our false positive rate was lower
especially when the diagnosis of vascular disproportion was made at third
trimester. The performance of fetal cardiac screening does not seem to be very
good, but prenatal diagnosis is probably not always possible: Among our three
false negative cases, two had isolated vascular disproportion and the third no
risk factors.
PMID- 25845940
TI - Dual-Chamber Stimulation with Single-Lead VDD Pacing System in Mustard Surgery.
AB - Sinus node disease is a problem encountered in patients after the Mustard
surgery, requiring a pacemaker implantation. The knowledge of the complexity
anatomy is crucial because of the possible challenges associated with this
procedure. We report a case of a 24-year-old woman presented with symptomatic
bradycardia, in which a bicameral stimulation using a single-lead VDD pacing
system was successfully performed.
PMID- 25845941
TI - In-line Filtration Decreases Systemic Inflammatory Response Syndrome, Renal and
Hematologic Dysfunction in Pediatric Cardiac Intensive Care Patients.
AB - Cardiac surgery with cardiopulmonary bypass (CPB) frequently leads to systemic
inflammatory response syndrome (SIRS) with concomitant organ malfunction. Infused
particles may exacerbate inflammatory syndromes since they activate the
coagulation cascade and alter inflammatory response or microvascular perfusion.
In a randomized, controlled, prospective trial, we have previously shown that
particle-retentive in-line filtration prevented major complications in critically
ill children. Now, we investigated the effect of in-line filtration on major
complications in the subgroup of cardiac patients. Children admitted to tertiary
pediatric intensive care unit were randomized to either control or filter group
obtaining in-line filtration throughout complete infusion therapy. Risk
differences and 95 % confidence intervals (CI) of several complications such as
SIRS, sepsis, mortality, various organ failure and dysfunction were compared
between both groups using the Wald method. 305 children (n = 150 control, n = 155
filter group) with cardiac diseases were finally analyzed. The majority was
admitted after cardiac surgery with CPB. Risk of SIRS (-11.3 %; 95 % CI -21.8 to
0.5 %), renal (-10.0 %; 95 % CI -17.0 to -3.0 %) and hematologic (-8.1 %; 95 % CI
-14.2 to -0.2 %) dysfunction were significantly decreased within the filter
group. No risk differences were demonstrated for occurrence of sepsis, any other
organ failure or dysfunctions between both groups. Infused particles might
aggravate a systemic hypercoagulability and inflammation with subsequent organ
malfunction in pediatric cardiac intensive care patients. Particle-retentive in
line filtration might be effective in preventing SIRS and maintaining renal and
hematologic function. In-line filtration offers a novel therapeutic option to
decrease morbidity in cardiac intensive care.
PMID- 25845942
TI - Phenotype of Children with QT Prolongation Identified Using an Institution-Wide
QT Alert System.
AB - QT prolongation is an independent risk factor for cardiovascular mortality in
adults. However, there is little information available on pediatric patients with
QT prolongation and their outcomes. Herein, we evaluated the prevalence of QT
prolongation in pediatric patients identified by an institution-wide QT alert
system, and the spectrum of their phenotype. Patients with documented QT
prolongation on an ECG obtained between November 2010 and June 2011 were
included. There were 1303 pediatric ECGs, and 68 children had electrographically
isolated QT prolongation. Comprehensive review of medical records was performed
with particular attention to QT-prolonging clinical, laboratory, and medication
data, which were summarized into a pro-QTc score. Overall, 68 (5 %) pediatric
patients had isolated QT prolongation. The mean age of this pediatric cohort was
9 +/- 6 years, and the average QTc was 494 +/- 42 ms. All children had 1 or more
QT-prolonging risk factor(s), most commonly QT-prolonging medications. One
patient was identified with congenital long QT syndrome (LQTS), which was not
previously diagnosed. In one-year follow-up, only one pediatric death (non
cardiac) occurred (1.5 %). Potentially QT-offending/pro-arrhythmic medications
were changed in 80 % of pediatric patients after the physician received the QT
alert. Children with QT prolongation had very low mortality and minimal
polypharmacy. Still, medications and other modifiable conditions were the most
common causes of QT prolongation. Children with a prolonged QTc should be
evaluated for modifiable QT-prolonging factors. However, if no risk factors are
present or the QTc does not attenuate after risk factor modification/removal, the
child should be evaluated for congenital LQTS.
PMID- 25845943
TI - InSAC: A novel sub-nuclear body essential for Interleukin-6 and -10 RNA
processing and stability.
AB - Dysregulation of cytokine expression causes inflammatory diseases or chronic
infection conditions. We have identified that Tat-activating regulatory DNA
binding protein-43 (TDP-43) is involved in cytokine RNA processing in order to
promote an optimal immune response. The interaction of TDP-43 with spliceosomal
components from the Cajal body leads to the formation of a novel sub-nuclear body
called the Interleukin (IL)-6 and IL-10 Splicing Activating Compartment (InSAC).
TDP-43 binds to the IL-6 and IL-10 RNAs in a sequence-dependent manner. In cell
based studies, we observed that lipopolysaccharide (LPS) stimulation induces the
formation of the InSAC through TDP-43 ubiquitination, thereby influencing the
processing and expression levels of IL-6 RNA. Moreover, TDP-43 knockdown in vivo
results in a decrease in IL-6 production and its RNA splicing and stability.
Thus, these findings demonstrate that the InSAC is linked to the activation and
modulation of the immune response.
PMID- 25845944
TI - Broadly neutralizing antibodies against the rapidly evolving porcine reproductive
and respiratory syndrome virus.
AB - Neutralizing antibodies are a critical part of the immune armory for defense
against viruses, and the mechanism by which many effective vaccines work to
protect against viral infections. However, infections by rapidly evolving and
genetically diverse viruses are often characterized by ineffective neutralizing
antibody responses. Porcine reproductive and respiratory syndrome virus (PRRSV)
is a highly genetically diverse RNA virus that causes PRRS, the most significant
disease of pigs worldwide. The prevailing view of immunity to PRRSV is
characterized by delayed and ineffectual production of neutralizing antibodies
lacking cross-reactivity that is necessary for vaccine efficacy. Using an ELISA
based neutralizing assay developed to analyze PRRSV growth in porcine alveolar
macrophages, the naturally permissive cell of PRRSV, we showed that sera from
previously infected commercial sows had high levels of neutralizing activity
against diverse PRRSV strains, including across distinct genotypes of PRRSV.
Fifty percent cross-neutralization titers in excess of 1/1024 were observed.
Neutralizing activity was dose-dependent and was maintained in the immunoglobulin
fraction. Presence of high-titer, anti-PRRSV antibody activity that cross
neutralizes diverse strains of virus has prompted reevaluation of the role of
neutralizing antibodies for cross-protection against PRRSV under field
conditions. Understanding conditions that favor development of cross-neutralizing
activity will be crucial for improved strategies to enhance cross-protection
against PRRSV. More detailed studies are expected to elucidate mechanisms of
neutralizing antibody production and maturation and to investigate conserved
epitope targets of cross-neutralization in this rapidly evolving virus.
PMID- 25845945
TI - Development of an aerobic capacity prediction model from one-mile run/walk
performance in adolescents aged 13-16 years.
AB - A popular algorithm to predict VO2Peak from the one-mile run/walk test (1MRW)
includes body mass index (BMI), which manifests practical issues in school
settings. The purpose of this study was to develop an aerobic capacity model from
1MRW in adolescents independent of BMI. Cardiorespiratory endurance data were
collected on 90 adolescents aged 13-16 years. The 1MRW was administered on an
outside track and a laboratory VO2Peak test was conducted using a maximal
treadmill protocol. Multiple linear regression was employed to develop the
prediction model. Results yielded the following algorithm: VO2Peak = 7.34 * (1MRW
speed in m s(-1)) + 0.23 * (age * sex) + 17.75. The New Model displayed a
multiple correlation and prediction error of R = 0.81, standard error of the
estimate = 4.78 ml kg(-1) . min(-1), with measured VO2Peak and good criterion
referenced (CR) agreement into FITNESSGRAM's Healthy Fitness Zone (Kappa = 0.62;
percentage agreement = 84.4%; Phi = 0.62). The New Model was validated using k
fold cross-validation and showed homoscedastic residuals across the range of
predicted scores. The omission of BMI did not compromise accuracy of the model.
In conclusion, the New Model displayed good predictive accuracy and good CR
agreement with measured VO2Peak in adolescents aged 13-16 years.
PMID- 25845946
TI - Immunopathogenesis of Myocarditis: The Interplay Between Cardiac Fibroblast
Cells, Dendritic Cells, Macrophages and CD4+ T Cells.
AB - The myocardium responds to aetiologically different pathological injuries through
a common multistep process involving highly co-ordinated interactions between
cardiac and immune cells. Cardiac fibroblast cells which constitute the prevalent
cell type in the heart to have their functional effects that express contractile
proteins and exhibit increased migratory, proliferative and secretory properties.
During the pathogenesis of myocarditis, cardiac fibroblast, dendritic cells,
macrophages, CD4(+) T cells and other immune cells are known to play variable
roles. It is becoming increasingly clear that cardiac fibroblasts are not passive
players in immune responses, and several evidences show this through the release
of soluble signals and/or direct interactions with these immune cells. Typically,
fibroblasts are involved in synthesizing factors such as cytokines, chemokines,
prostanoids, matrix components and matrix-degrading enzymes to influence
dendritic cells, CD4(+) T cells and macrophage functions and vice versa in the
pathogenesis of myocarditis. Again, evidence proves a crosstalk between cardiac
fibroblasts and immune cells recruited into the myocardium during myocarditis in
the microenvironments. This piece reviews the properties and roles of cardiac
fibroblast cells, dendritic cells, macrophages and CD4(+) T cells in the
pathogenesis of myocarditis, and how these cells interplay on each other in the
microenvironment.
PMID- 25845947
TI - Are There Modifiable Risk Factors for Hospital Readmission After Total Hip
Arthroplasty in a US Healthcare System?
AB - BACKGROUND: Although total hip arthroplasty (THA) is a successful procedure, 4%
to 11% of patients who undergo THA are readmitted to the hospital. Prior studies
have reported rates and risk factors of THA readmission but have been limited to
single-center samples, administrative claims data, or Medicare patients. As a
result, hospital readmission risk factors for a large proportion of patients
undergoing THA are not fully understood. QUESTIONS/PURPOSES: (1) What is the
incidence of hospital readmissions after primary THA and the reasons for
readmission? (2) What are the risk factors for hospital readmissions in a large,
integrated healthcare system using current perioperative care protocols? METHODS:
The Kaiser Permanente (KP) Total Joint Replacement Registry (TJRR) was used to
identify all patients with primary unilateral THAs registered between January 1,
2009, and December 31, 2011. The KPTJRR's voluntary participation is 95%. A
logistic regression model was used to study the relationship of risk factors
(including patient, clinical, and system-related) and the likelihood of 30-day
readmission. Readmissions were identified using electronic health and claims
records to capture readmissions within and outside the system. Odds ratio (OR)
and 95% confidence intervals (CIs) were calculated. Of the 12,030 patients
undergoing primary THAs included in the study, 59% (n = 7093) were women and
average patient age was 66.5 years (+/- 10.7). RESULTS: There were 436 (3.6%)
patients with hospital readmissions within 30 days of the index procedure. The
most common reasons for readmission were infection and inflammatory reaction
resulting from internal joint prosthetic (International Classification of
Diseases, 9(th) Revision, Clinical Modification [ICD-9-CM] 996.66, 7.0%); other
postoperative infection (ICD-9-CM 998:59, 5.5%); unspecified septicemia (ICD-9-CM
038.9, 4.9%); and dislocation of a prosthetic joint (ICD-9-CM 996.42, 4.7%). In
adjusted models, the following factors were associated with an increased
likelihood of 30-day readmission: medical complications (OR, 2.80; 95% CI, 1.59
4.93); discharge to facilities other than home (OR, 1.89; 95% CI, 1.39-2.58);
length of stay of 5 or more days (OR, 1.80; 95% CI, 1.22-2.65) versus 3 days;
morbid obesity (OR, 1.74; 95% CI, 1.25-2.43); surgeries performed by high-volume
surgeons compared with medium volume (OR, 1.53; 95% CI, 1.14-2.08); procedures at
lower-volume (OR, 1.41; 95% CI, 1.07-1.85) and medium-volume hospitals (OR, 1.81;
95% CI, 1.20-2.72) compared with high-volume ones; sex (men: OR, 1.51; 95% CI,
1.18-1.92); obesity (OR, 1.32; 95% CI, 1.02-1.72); race (black: OR, 1.26; 95% CI,
1.02-1.57); increasing age (OR, 1.03; 95% CI, 1.01-1.04); and certain
comorbidities (pulmonary circulation disease, chronic pulmonary disease,
hypothyroidism, and psychoses). CONCLUSIONS: The 30-day hospital readmission rate
after primary THA was 3.6%. Modifiable factors, including obesity, comorbidities,
medical complications, and system-related factors (hospital), have the potential
to be addressed by improving the health of patients before this elective
procedure, patient and family education and planning, and with the development of
high-volume centers of excellence. Nonmodifiable factors such as age, sex, and
race can be used to establish patient and family expectations regarding risk of
readmission after THA. Contrary to other studies and the finding of increased
hospital volume associated with lower risk of readmission, higher volume surgeons
had a higher risk of patient readmission, which may be attributable to the
referral patterns in our organization. LEVEL OF EVIDENCE: Level III, therapeutic
study.
PMID- 25845948
TI - Morbid Obesity: Increased Risk of Failure After Aseptic Revision TKA.
AB - BACKGROUND: Patients with obesity are known to have a higher risk of
complications after primary TKA; however, there is a paucity of data regarding
the effects of obesity with revision TKAs. QUESTIONS/PURPOSES: We asked the
following questions : (1) Are patients with morbid obesity (BMI>=40 kg/m2) at
greater risk for repeat revision, reoperation, or periprosthetic joint infection
(PJI) compared with patients without obesity (BMI<30 kg/m2) after an index
revision TKA performed for aseptic reasons? (2) Do patients who are not obese
achieve higher Knee Society pain and function scores after revision TKA for
aseptic reasons? METHODS: We used a retrospective cohort study with 1:1 matching
for sex, age (+/-3 years) and date of surgery (+/-1 year) to compare patients
with morbid obesity with patients without obesity with respect to repeat
revision, reoperation, and PJI. Using our institution's total joint registry, we
identified 1291 index both-component (femoral and tibial) aseptic revision TKAs
performed during a 15-year period (1992-2007). Of these, 120 revisions were in
patients with morbid obesity (BMI>=40 kg/m2) and 624 were in patients with a BMI
less than 30 kg/m2. We then considered only patients with a minimum 5-year
followup, which was available for 77% of patients with morbid obesity and 76% of
patients with a BMI less than 30 kg/m2 (p=0.84). All patients with morbid obesity
who met criteria were included (morbid obesity group: n=93; average followup, 7.9
years) and compared with a matched cohort of patients with a BMI less than 30
kg/m2 (nonmorbid obesity group: n=93; average followup, 7.3 years). Medical
records were reviewed to gather details regarding complications and clinical
outcomes. RESULTS: Overall, patients with morbid obesity had an increased risk of
repeat revision (hazard ratio [HR], 3.8; 95% CI, 1.2-16.5; p<0.02), reoperation
(HR, 2.9; 95% CI, 1.3-7.4; p<0.02), and PJI (HR, 6.4; 95% CI, 1.2-119.7; p<0.03).
Implant survival rates were 96% (95% CI, 92%-100%) and 100% at 5 years, and 81%
(95% CI, 70%-92%) and 93% (95% CI, 86%-100%) at 10 years for the patients with
morbid obesity and those without morbid obesity, respectively (p=0.02). At 10
years, The Knee Society pain (90 [95% CI, 88-92] vs 76 [95% CI, 71-81]; p<0.01)
and function (61 [95% CI, 53-69] vs 57 [95% CI, 42-52]; p<0.01) scores were
higher in patients with a BMI less than 30 kg/m2 compared with patients with
morbid obesity. CONCLUSION: Morbid obesity is associated with increased rates of
rerevision, reoperation, and PJI after aseptic revision TKA. As the time
sensitive nature of revision surgery may not always allow for patient or
comorbidity optimization, these results emphasize the need for improving our care
of patients with morbid obesity earlier on during the osteoarthritic process.
Additional studies are needed to risk stratify patients in the morbidly obese
population to better guide patient selection and effective optimization. LEVEL OF
EVIDENCE: Level III, therapeutic study.
PMID- 25845950
TI - Art in science: the stage of the human body--the anatomical theatre of Bologna.
PMID- 25845949
TI - Does Combined Intra- and Extraarticular ACL Reconstruction Improve Function and
Stability? A Meta-analysis.
AB - BACKGROUND: ACL reconstruction aims to restore knee function and stability;
however, rotational stability may not be completely restored by use of standard
intraarticular reconstruction alone. Although individual studies have not shown
the superiority of combined ACL reconstruction compared with isolated
intraarticular reconstruction in terms of function and stability, biomechanical
principles suggest a combined approach may be helpful, therefore pooling (meta
analyzing) the available randomized clinical studies may be enlightening.
QUESTIONS/PURPOSES: We performed a meta-analysis to determine whether combining
extraarticular with intraarticular ACL reconstruction would lead to: (1) similar
knee function measured by the IKDC evaluation, return-to-activity, and Tegner
Lysholm scores, compared with isolated intraarticular reconstruction; (2)
increased stability measured by pivot shift and instrumented Lachman examination;
and (3) any differences in complications and adverse events? METHODS: To identify
randomized controlled trials (RCTs) comparing combined intra- and extrarticular
ACL reconstruction (combined reconstruction) with intraarticular ACL
reconstruction only, we searched MEDLINE, EMBASE, SPORTDiscus, Latin American and
Caribbean Health Sciences (LILACS), and the Cochrane Central Register of
Controlled Trials, and followed the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) criteria. The main outcomes we sought were
patient function and stability and complications after ACL reconstruction. Of 386
identified studies, eight RCTs were included (n=682 participants; followup, 12-84
months; men to women ratio, 2.17:1) in our meta-analysis. Study quality (internal
validity) was assessed using the Cochrane risk-of-bias tool; in general, we found
a moderate quality of evidence of the included studies. RESULTS: When functional
outcomes were compared, we found no difference between patients who underwent
intraarticular ACL reconstruction only and those who underwent combined
reconstruction (IKDC, return-to-activity, and Tegner Lysholm scores). However,
patients who underwent combined reconstruction were more likely to show improved
stability based on the pivot shift test (risk ratio [RR], 0.95; 95% CI, 0.91
0.99; p=0.02) and Lachman test (RR, 0.93; 95% CI, 0.88-0.98; p=0.01). In
addition, our meta-analysis found no difference between the two treatments in
terms of general complications or adverse events (RR, 1.31; 95% CI, 0.70-2.34;
p=0.40) and the proportion of patients whose reconstructions failed (RR, 2.88;
95% CI, 0.73-11.47; p=0.13). CONCLUSION: Combined intra- and extraarticular ACL
reconstruction provided marginally improved knee stability and comparable failure
rates but no difference in patient-reported functional outcomes scores.
Complications and adverse events such as knee stiffness may be underreported and
technical factors such as graft placement were difficult to evaluate. Future
studies are needed to determine whether the small differences in additional
stability warrant the potential morbidity of the additional extraarticular
procedure and to determine long-term failure rates.
PMID- 25845951
TI - Not the Last Word: Geriatric Hip Fracture Centers: The Time Has Come.
PMID- 25845952
TI - 2015 RIV Abstracts.
AB - This supplement can be found at the following link: http://www.shmabstracts.com.
PMID- 25845953
TI - Current Indications for Implantable Cardioverter Defibrillators in Non-Ischemic
Cardiomyopathies and Channelopathies.
AB - Current indications for implantable cardioverter defibrillators (ICDs) in
patients with channelopathies and cardiomyopathies of non-ischemic origin are
mainly based on non-randomized evidence. In patients with nonischemic dilated
cardiomyopathy (NIDCM), there is a tendency towards a beneficial effect on total
mortality of ICD therapy in patients with significant left ventricular (LV)
dysfunction. Although an important reduction in sudden cardiac death (SCD) seems
to be clearly demonstrated in these patients, a net beneficial effect on total
mortality is unclear mostly in cases with good functional status. Risk
stratification has been changing over the last two decades in patients with
hypertrophic cardiomyopathy (HCM). Its risk profile has been delineated in
parallel with the beneficial effect of ICD in high risk patients. Observational
results based on "appropriate" ICD interventions do support its usefulness both
in primary and secondary SCD prevention in these patients. Novel risk models
quantify the rate of sudden cardiac death in these patients on individual basis.
Less clear risk stratification is available for cases of arrhythmogenic right
ventricular cardiomyopathy (ARVC) and in other uncommon familiar
cardiomyopathies. Main features of risk stratification vary among the different
channelopathies (long QT syndrome -LQTS-, Brugada syndrome, etc) with great
debate on the management of asymptomatic patients. For most familiar
cardiomyopathies, ICD therapy is the only accepted strategy in the prevention of
SCD. So far, genetic testing has a limited role in risk evaluation and management
of the individual patient. This review aims to summarize these criticisms and to
refine the current indications of ICD implantation in patients with
cardiomyopathies and major channelopathies.
PMID- 25845954
TI - Insulin resistance is associated with impaired cardiac sympathetic innervation in
patients with heart failure.
AB - AIMS: Insulin resistance (IR) represents, at the same time, cause and consequence
of heart failure (HF) and affects prognosis in HF patients, but
pathophysiological mechanisms remain unclear. Hyperinsulinemia, which
characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR
is associated with impaired cardiac sympathetic innervation in HF. Yet, this
hypothesis has never been investigated. Aim of the present observational study
was to assess the relationship between IR and cardiac sympathetic innervation in
non-diabetic HF patients. METHODS AND RESULTS: One hundred and fifteen patients
(87% males; 65 +/- 11.3 years) with severe-to-moderate HF (ejection fraction 32.5
+/- 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial
scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment
Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From
(123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout
rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non
IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M
ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were
significantly reduced in IR compared with non-IR patients. Early and late H/M
ratio showed significant inverse correlation with fasting insulinemia and HOMA
IR. CONCLUSION: Cardiac sympathetic innervation is more impaired in patients with
IR and HF compared with matched non-IR patients. These findings shed light on the
relationship among IR, HF, and cardiac sympathetic nervous system. Additional
studies are needed to clarify the pathogenetic relationship between IR and HF.
PMID- 25845955
TI - Medial rectus muscle elongation, a technique to treat very large-angle esotropia.
AB - PURPOSE: The purpose was to describe the medial rectus muscle elongation (MRE)
procedure to treat very large-angle esotropia (ET) with surgery on a lower number
of muscles. METHODS: Twenty patients with very large-angle ET (more than 70 PD)
underwent the MRE procedure. In the MRE procedure, the muscle was split
longitudinally into three parts. The wider central part was sutured with 6/0
vicryl and disinserted. The distal end of the peripheral parts (still attached to
the original insertion), 7-9 mm away from the insertion, was sutured to the
proximal end of the central part. At the end of the procedure, the distance of
the anastomosis site from the insertion was named as the final elongation. The
dose-response effect of the final elongation was calculated in bilateral MRE
cases. The mean of the dose-response effect, obtained in the binocular surgery
group, was used in the monocular surgery group to calculate the resection effect
of lateral rectus (LR) muscle. RESULTS: Eleven patients underwent bilateral MRE
and nine patients underwent unilateral MRE and LR muscle resection. The mean
preoperative far and near deviation was 94.10 +/- 19.33 PD. The mean
postoperative deviation was 14.60 +/- 18.07 PD for far and 14.50 +/- 18.23 PD for
near deviation. In bilateral MRE cases, the mean dose-response effect of the
elongation was 5.53 +/- 0.67 PD/mm for far and 5.58 +/- 0.69 PD/mm for near
deviation. The mean LR muscle resection effect was 6.41 +/- 1.99 PD/mm for far
and 6.28 +/- 1.93 PD/mm for near deviation. CONCLUSION: The MRE procedure seems
an acceptable method to treat very large-angle ET with surgery on a lower number
of muscles.
PMID- 25845956
TI - Feeding performance of king Mackerel, Scomberomorus cavalla.
AB - Feeding performance is an organism's ability to capture and handle prey. Although
bite force is a commonly used metric of feeding performance, other factors such
as bite pressure and strike speed are also likely to affect prey capture.
Therefore, this study investigated static bite force, dynamic speeds, and
predator and prey forces resulting from ram strikes, as well as bite pressure of
the king mackerel, Scomberomorus cavalla, in order to examine their relative
contributions to overall feeding performance. Theoretical posterior bite force
ranged from 14.0-318.7 N. Ram speed, recorded with a rod and reel incorporated
with a line counter and video camera, ranged from 3.3-15.8B L/s. Impact forces on
the prey ranged from 0.1-1.9 N. Bite pressure, estimated using theoretical bite
forces at three gape angles and tooth cross-sectional areas, ranged from 1.7-56.9
MPa. Mass-specific bite force for king mackerel is relatively low in comparison
with other bony fishes and sharks, with relatively little impact force applied to
the prey during the strike. This suggests that king mackerel rely on high
velocity chases and high bite pressure generated via sharp, laterally compressed
teeth to maximize feeding performance.
PMID- 25845957
TI - Words of wisdom. Re: Might men diagnosed with metastatic prostate cancer benefit
from definitive treatment of the primary tumour? A SEER-based study.
PMID- 25845958
TI - Words of wisdom. Re: Dissecting the association between metabolic syndrome and
prostate cancer risk: analysis of a large clinical cohort.
PMID- 25845959
TI - Words of wisdom. Re: Association between metabolic syndrome and severity of lower
urinary tract symptoms: an observational study in a 4666 European men cohort.
PMID- 25845960
TI - Words of wisdom. Re: Surgical outcomes in the management of isolated nodal
recurrences: a multicenter, international retrospective cohort.
PMID- 25845961
TI - Words of wisdom. Re: MPDL3280A (anti-PD-L1) treatment leads to clinical activity
in metastatic bladder cancer.
PMID- 25845962
TI - Words of wisdom. Re: GreenLightTM laser (XPS) photoselective vapo-enucleation
versus holmium laser enucleation of the prostate for the treatment of symptomatic
benign prostate hyperplasia: a randomized controlled study.
PMID- 25845964
TI - Interaction of Blood Pressure and Body Mass Index With Risk of Incident Atrial
Fibrillation in a Japanese Urban Cohort: The Suita Study.
AB - BACKGROUND AND PURPOSE: To prevent stroke, strategies for atrial fibrillation
(AF) prevention and an early detection of AF by electrocardiogram are essential.
However, only a limited prospective studies have examined the risk factors for
AF, even in blood pressure (BP) and body mass index (BMI), which are not clear
among general populations. We investigated the impacts of BP and BMI on the risk
of incident AF in a general population. METHODS: A total of 6,906 participants
(30-84 years) in the Suita Study were prospectively followed up for incident AF.
Participants were diagnosed with AF if AF or atrial flutter was present on an
electrocardiogram from a routine health examination (every 2 years) or if AF was
indicated as a present illness from health examinations and/or medical records
during follow-up. Adjusted Cox proportional hazard ratios (HRs) were calculated.
RESULTS: During the 12.8-year follow-up, 253 incident AF events occurred.
Compared with the systolic BP (SBP) < 120 mm Hg and normal-weight, the adjusted
HRs (95% confidence intervals; CIs) of incident AF in the systolic hypertension
and the overweight (BMI >= 25kg/m(2)) groups were 1.74 (1.22-2.49) and 1.35 (1.01
1.80), respectively. Compared with SBP < 120 mm Hg and normal weight, the
adjusted HRs (95% CIs) of incident AF in the SBP = 120-139 mm Hg with overweight
and the systolic hypertension with normal or overweight were 1.72 (1.01-2.91),
1.66 (1.10-2.50), and 2.31 (1.47-3.65), respectively (P for interaction = 0.04).
CONCLUSIONS: Systolic prehypertension and overweight are associated with incident
AF in Japanese population. The association between SBP and AF may be evident by
overweight.
PMID- 25845965
TI - 7 Tesla MRI in cerebral small vessel disease.
AB - Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive
decline. Magnetic resonance imaging (MRI) currently plays a central role in
diagnosis, and advanced MRI techniques are widely used in research but are
limited by spatial resolution. Human 7 Tesla (7T) MRI has recently become
available offering the ability to image at higher spatial resolution. This may
provide additional insights into both the vascular pathology itself as well as
parenchymal markers which could only previously be examined post mortem. In this
review we cover the advantages and limitations of 7T MRI, review studies in SVD
performed to date, and discuss potential future insights into SVD which 7T MRI
may provide.
PMID- 25845967
TI - Why What Is Counterfactual Really Matters: A Response to Weisberg and Gopnik ().
PMID- 25845966
TI - High risk of delisting or death in liver transplant candidates following
infections: Results from the North American Consortium for the Study of End-Stage
Liver Disease.
AB - Because Model for End-Stage Liver Disease (MELD) scores at the time of liver
transplantation (LT) increase nationwide, patients are at an increased risk for
delisting by becoming too sick or dying while awaiting transplantation. We
quantified the risk and defined the predictors of delisting or death in patients
with cirrhosis hospitalized with an infection. North American Consortium for the
Study of End-Stage Liver Disease (NACSELD) is a 15-center consortium of tertiary
care hepatology centers that prospectively enroll and collect data on infected
patients with cirrhosis. Of the 413 patients evaluated, 136 were listed for LT.
The listed patients' median age was 55.18 years, 58% were male, and 47% were
hepatitis C virus infected, with a mean MELD score of 2303. At 6-month follow-up,
42% (57/136) of patients were delisted/died, 35% (47/136) underwent
transplantation, and 24% (32/136) remained listed for transplant. The frequency
and types of infection were similar among all 3 groups. MELD scores were highest
in those who were delisted/died and were lowest in those remaining listed (25.07,
24.26, 17.59, respectively; P < 0.001). Those who were delisted or died, rather
than those who underwent transplantation or were awaiting transplantation, had
the highest proportion of 3 or 4 organ failures at hospitalization versus those
transplanted or those continuing to await LT (38%, 11%, and 3%, respectively; P =
0.004). For those who were delisted or died, underwent transplantation, or were
awaiting transplantation, organ failures were dominated by respiratory (41%, 17%,
and 3%, respectively; P < 0.001) and circulatory failures (42%, 16%, and 3%,
respectively; P < 0.001). LT-listed patients with end-stage liver disease and
infection have a 42% risk of delisting/death within a 6-month period following an
admission. The number of organ failures was highly predictive of the risk for
delisting/death. Strategies focusing on prevention of infections and extrahepatic
organ failure in listed patients with cirrhosis are required.
PMID- 25845968
TI - Sorafenib enhances the antitumor effects of anti-CTLA-4 antibody in a murine
cancer model by inhibiting myeloid-derived suppressor cells.
AB - This antitumor effect of sorafenib is considered to be dependent not only on its
direct cytotoxicity to cancer cells but also due to the inhibition of myeloid
derived suppressor cells (MDSCs). Recently, a novel antibody against cytotoxic T
lymphocyte antigen 4 (CTLA-4), which activates lymphocytes, is currently in
clinical applications. The aim of the present study was to investigate the
synergistic antitumor effects of anti-CTLA-4 antibody (Ab) and sorafenib in a
murine cancer model. RENCA cells were subcutaneously inoculated into mice, which
were randomly divided into 4 treatment groups: sorafenib plus anti-CTLA-4 Ab,
sorafenib plus control Ab, vehicle plus anti-CTLA-4 Ab, and vehicle plus control
Ab. Single therapy using anti-CTLA-4 Ab suppressed tumor growth, but no
difference was noted when compared with the single therapy group using sorafenib.
Notably, the greatest decrease in tumor size was noted with sorafenib plus anti
CTLA-4 Ab (combination therapy), and the highest rate of tumor rejection was
observed in the combination therapy group. The number of infiltrating CD4- or CD8
positive lymphocytes was strongly increased in the combination therapy group.
These in vivo data indicate that sorafenib increased the immunostimulatory effect
of anti-CTLA-4 Ab even when sorafenib was used at a low dose. An in vitro study
using MDSCs and CD8(+) T cells showed that the inhibitory effect of MDSCs on
CD8(+) T cells was significantly abrogated by the combined use of sorafenib and
anti-CTLA-4 Ab. Sorafenib suppressed the expression of immunosuppressive factors
in MDSCs. These data indicate that combination therapy of sorafenib and anti-CTLA
4 Ab may be effective in advanced kidney cancer patients.
PMID- 25845973
TI - Comparison of phase-constrained parallel MRI approaches: Analogies and
differences.
AB - PURPOSE: Phase-constrained parallel MRI approaches have the potential for
significantly improving the image quality of accelerated MRI scans. The purpose
of this study was to investigate the properties of two different phase
constrained parallel MRI formulations, namely the standard phase-constrained
approach and the virtual conjugate coil (VCC) concept utilizing conjugate k-space
symmetry. METHODS: Both formulations were combined with image-domain algorithms
(SENSE) and a mathematical analysis was performed. Furthermore, the VCC concept
was combined with k-space algorithms (GRAPPA and ESPIRiT) for image
reconstruction. In vivo experiments were conducted to illustrate analogies and
differences between the individual methods. Furthermore, a simple method of
improving the signal-to-noise ratio by modifying the sampling scheme was
implemented. RESULTS: For SENSE, the VCC concept was mathematically equivalent to
the standard phase-constrained formulation and therefore yielded identical
results. In conjunction with k-space algorithms, the VCC concept provided more
robust results when only a limited amount of calibration data were available.
Additionally, VCC-GRAPPA reconstructed images provided spatial phase information
with full resolution. CONCLUSIONS: Although both phase-constrained parallel MRI
formulations are very similar conceptually, there exist important differences
between image-domain and k-space domain reconstructions regarding the calibration
robustness and the availability of high-resolution phase information.
PMID- 25845974
TI - Phosphorylation of the cell division protein GpsB regulates PrkC kinase activity
through a negative feedback loop in Bacillus subtilis.
AB - Although many membrane Ser/Thr-kinases with PASTA motifs have been shown to
control bacterial cell division and morphogenesis, inactivation of the Ser/Thr
kinase PrkC does not impact Bacillus subtilis cell division. In this study, we
show that PrkC localizes at the division septum. In addition, three proteins
involved in cell division/elongation, GpsB, DivIVA and EzrA are required for
stimulating PrkC activity in vivo. We show that GpsB interacts with the catalytic
subunit of PrkC that, in turn, phosphorylates GpsB. These observations are not
made with DivIVA and EzrA. Consistent with the phosphorylated residue previously
detected for GpsB in a high-throughput phosphoproteomic analysis of B. subtilis,
we show that threonine 75 is the single PrkC-mediated phosphorylation site in
GpsB. Importantly, the substitution of this threonine by a phospho-mimetic
residue induces a loss of PrkC kinase activity in vivo and a reduced growth under
high salt conditions as observed for gpsB and prkC null mutants. Conversely,
substitution of threonine 75 by a phospho-ablative residue does not induce such
growth and PrkC kinase activity defects. Altogether, these data show that
proteins of the divisome control PrkC activity and thereby phosphorylation of
PrkC substrates through a negative feedback loop in B. subtilis.
PMID- 25845975
TI - Variable risk of atopic disease due to indoor fungal exposure in NHANES 2005
2006.
AB - BACKGROUND: Exposure to damp indoor environments is associated with increased
risk of eczema, allergy and asthma. The role of dampness-related exposures and
risk of allergic diseases are yet to be fully explored in the US population.
OBJECTIVE: We assess whether exposure to fungi, house dust mites and endotoxin
increases the risk of eczema, allergy and asthma in children and adults
participating in NHANES 2005-2006. METHODS: A total of 8412 participants (2849
were children aged between 6 and 17 years) were recruited in the 2005-2006
survey. We used multiple logistic regression to investigate whether mildew/musty
odour and increased concentrations of Alternaria alternata allergen, Aspergillus
fumigatus antigens, house dust mite and endotoxin antigens increase the risk of
eczema, allergy and asthma. We stratified models by total IgE < 170 and >= 170
KU/L to assess allergic and non-allergic asthma outcomes. Exposure to multiple
biological agents and risk of reporting eczema, allergy and asthma were also
investigated. RESULTS: Reporting of a mildew/musty odour was associated with
increased risk of childhood asthma (OR 1.60; 95% CI 1.17-2.19), and adult eczema,
allergy and asthma (OR 1.92; 95% CI 1.39-2.63, OR 1.59 95% CI 1.26-2.02 and OR
1.61 95% CI 1.00-2.57, respectively). Risk of asthma was associated with total
IgE >= 170 KU/L in children (OR 1.81; 95% CI 1.01-3.25) and total IgE < 170 KU/L
in adults (OR 1.91; 95% CI 1.07-3.42). Children and adults exposed to more than
eight biological agents present in the home were at reduced risk of eczema (OR
0.17; 95% CI 0.04-0.77) and asthma (OR 0.49; 95% CI 0.25-0.97), respectively.
CONCLUSION: Exposure to a mildew/musty odour, as a proxy for exposure to fungus,
was implicated in an increased risk of atopic diseases. Sensitisation may play a
different role in children and adults, and exposure to multiple allergens may
reduce the risk of atopic disease.
PMID- 25845976
TI - Completely organic multilayer thin film with thermoelectric power factor rivaling
inorganic tellurides.
AB - Composed exclusively of organic components, polyaniline (PANi), graphene, and
double-walled nanotubes (DWNTs) are alternately deposited from aqueous solutions
using a layer-by-layer assembly. The 40 quadlayer thin film (470 nm thick)
exhibits electrical conductivity of 1.08 * 10(5) S m(-1) and a Seebeck
coefficient of 130 MUV K(-1) , producing a thermoelectric power factor of 1825
MUW m(-1) K(-2) .
PMID- 25845977
TI - Potential bias due to outcome-related loss to follow-up in cohort studies on
incidence of drug injection: systematic review and meta-analysis.
AB - AIMS: A systematic review and meta-analysis were conducted to synthesize results
from cohort studies on initiation into drug injection among vulnerable
populations, to quantify heterogeneity in the estimated incidence rates of drug
injection and to identify potential sources of heterogeneity and bias. METHODS:
MEDLINE, EMBASE, PsycINFO and LILACS were searched for relevant studies published
between 1980 and 2012. Investigators independently reviewed studies for
inclusion, retrieved information on baseline population characteristics and
follow-up features and assessed study quality. Study-specific incidence rates of
drug injection were calculated as the number of new injectors divided by the
person-years at risk. The I(2) statistic was used to quantify heterogeneity in
incidence rates across studies, and random-effects meta-regression models were
used to identify determinants of heterogeneity and bias. RESULTS: Nine cohorts
totalling 1843 participants met the inclusion criteria, with individual sample
sizes of 70-415 participants and follow-up lengths of 6 months-3.4 years. The
incidence of drug injection varied widely, from 2.1 to 24.2 cases per 100 person
years. The strong between-study heterogeneity (I(2) = 90%, P<0.001) was reduced
significantly after accounting for the different follow-up lengths (I(2) = 17%,
P = 0.30), with a 57% (95% confidence interval 46-66%) decrease in the pooled
incidence of drug injection per 1-year increase in average follow-up.
CONCLUSIONS: The incidence of drug injection decreases sharply with increasing
follow-up length in cohort studies on drug injection initiation. Low retention
rates and potential for downward selection bias in cohort studies on drug
injection initiation are caused primarily by greater loss to follow-up among
individuals at higher risk of starting injection, compared with other
participants.
PMID- 25845978
TI - A prospective randomized blinded clinical trial: large-volume nasal irrigation
with fluticasone propionate in the early postoperative period following
septoplasty.
AB - BACKGROUND: The aim of this study was to compare 2 methods of nasal irrigation
after septoplasty. The combined use of low-pressure, high-volume nasal saline
(LPHVNS) irrigation, together with fluticasone propionate (FP) (LPHVNS+FP), was
compared with high-pressure, low-volume nasal saline (HPLVNS) irrigation during
the early postoperative period following septoplasty. METHODS: Seventy-three
patients undergoing septoplasty for nasal obstruction were recruited for the
study. The patients were randomly divided into 2 groups; nasal irrigation was
applied for 4 weeks in both groups. Group 1 (n = 40) used HPLVNS irrigation.
Group 2 (n = 33) used the LPHVNS+FP combination. The patients were evaluated
using the visual analogue scale (VAS), Nasal Obstruction Symptom Evaluation
(NOSE), nasal examination scores, acoustic rhinometry, rhinomanometry, and peak
nasal inspiratory flowmetry (PNIF) measurements. RESULTS: In group 2, the
increase in VAS results was more prominent than in group 1. NOSE scores were
significantly lower in group 2 than in group 1. The nasal examination revealed
that group 2 had less edema and less crusting than group 1. The decrease in nasal
airway resistance was significantly higher in group 2. The PNIF values increased
to a significantly greater extent in group 2 than in group 1. CONCLUSION: Nasal
irrigation with the LPHVNS+FP combination during the early postoperative period
following septoplasty is an effective method, resulting not only in increased
patient satisfaction and nasal air flow but also in decreased edema and crust
formation.
PMID- 25845979
TI - Role of c-Myb in chondrogenesis.
AB - The Myb locus encodes the c-Myb transcription factor involved in controlling a
broad variety of cellular processes. Recently, it has been shown that c-Myb may
play a specific role in hard tissue formation; however, all of these results were
gathered from an analysis of intramembranous ossification. To investigate a
possible role of c-Myb in endochondral ossification, we carried out our study on
the long bones of mouse limbs during embryonic development. Firstly, the c-myb
expression pattern was analyzed by in situ hybridization during endochondral
ossification of long bones. c-myb positive areas were found in proliferating as
well as hypertrophic zones of the growth plate. At early embryonic stages,
localized expression was also observed in the perichondrium and interdigital
areas. The c-Myb protein was found in proliferating chondrocytes and in the
perichondrium of the forelimb bones (E14.5-E17.5). Furthermore, protein was
detected in pre-hypertrophic as well as hypertrophic chondrocytes. Gain-of
function and loss-of-function approaches were used to test the effect of altered
c-myb expression on chondrogenesis in micromass cultures established from
forelimb buds of mouse embryos. A loss-of-function approach using c-myb specific
siRNA decreased nodule formation, as well as downregulated the level of Sox9
expression, a major marker of chondrogenesis. Transient c-myb overexpression
markedly increased the formation of cartilage nodules and the production of
extracellular matrix as detected by intense staining with Alcian blue. Moreover,
the expression of early chondrogenic genes such as Sox9, Col2a1 and activity of a
Col2-LUC reporter were increased in the cells overexpressing c-myb while late
chondrogenic markers such as Col10a1 and Mmp13 were not significantly changed or
were downregulated. Taken together, the results of this study demonstrate that
the c-Myb transcription factor is involved in the regulation and promotion of
endochondral bone formation.
PMID- 25845980
TI - Association of telomere length and mitochondrial DNA copy number in a community
sample of healthy adults.
AB - Cellular aging plays a role in longevity and senescence, and has been implicated
in medical and psychiatric conditions, including heart disease, cancer, major
depression and posttraumatic stress disorder. Telomere shortening and
mitochondrial dysfunction are thought to be central to the cellular aging
process. The present study examined the association between mitochondrial DNA
(mtDNA) copy number and telomere length in a sample of medically healthy adults.
Participants (total n=392) were divided into 4 groups based on the presence or
absence of early life adversity and lifetime psychopathology: No Adversity/No
Disorder, n=136; Adversity/No Disorder, n=91; No Adversity/Disorder, n=46;
Adversity/Disorder, n=119. Telomere length and mtDNA copy number were measured
using quantitative polymerase chain reaction. There was a positive correlation
between mtDNA and telomere length in the entire sample (r=0.120, p<0.001) and in
each of the four groups of participants (No Adversity/No Disorder, r=0.291,
p=0.001; Adversity/No Disorder r=0.279, p=0.007; No Adversity/Disorder r=0.449,
p=0.002; Adversity/Disorder, r=0.558, p<0.001). These correlations remained
significant when controlling for age, smoking, and body mass index and establish
an association between mtDNA and telomere length in a large group of women and
men both with and without early adversity and psychopathology, suggesting co
regulation of telomeres and mitochondrial function. The mechanisms underlying
this association may be important in the pathophysiology of age-related medical
conditions, such as heart disease and cancer, as well as for stress-associated
psychiatric disorders.
PMID- 25845982
TI - Preliminary investigation of flexibility in learning color-reward associations in
gibbons (Hylobatidae).
AB - Previous studies in learning set formation have shown that most animal species
can learn to learn with subsequent novel presentations being solved in fewer
presentations than when they first encounter a task. Gibbons (Hylobatidae) have
generally struggled with these tasks and do not show the learning to learn
pattern found in other species. This is surprising given their phylogenetic
position and level of cortical development. However, there have been conflicting
results with some studies demonstrating higher level learning abilities in these
small apes. This study attempts to clarify whether gibbons can in fact use
knowledge gained during one learning task to facilitate performance on a similar,
but novel problem that would be a precursor to development of a learning set. We
tested 16 captive gibbons' ability to associate color cues with provisioned food
items in two experiments where they experienced a period of learning followed by
experimental trials during which they could potentially use knowledge gained in
their first learning experience to facilitate solution I subsequent novel tasks.
Our results are similar to most previous studies in that there was no evidence of
gibbons being able to use previously acquired knowledge to solve a novel task.
However, once the learning association was made, the gibbons performed well above
chance. We found no differences across color associations, indicating learning
was not affected by the particular color / reward association. However, there
were variations in learning performance with regard to genera. The hoolock
(Hoolock leuconedys) and siamang (Symphalangus syndactylus) learned the fastest
and the lar group (Hylobates sp.) learned the slowest. We caution these results
could be due to the small sample size and because of the captive environment in
which these gibbons were raised. However, it is likely that environmental
variability in the native habitats of the subjects tested could facilitate the
evolution of flexible learning in some genera. Further comparative study is
necessary in order to incorporate realistic cognitive variables into foraging
models.
PMID- 25845981
TI - Umbilical cord blood transplantation in adults with advanced hodgkin's disease:
high incidence of post-transplant lymphoproliferative disease.
AB - We report the outcome of 30 consecutive patients with Hodgkin disease (HD) who
underwent single-unit UCBT. Most (90%) patients had failed previous autologous
hematopoietic stem cell transplantation. The conditioning regimens were based on
combinations of thiotepa, busulfan, cyclophosphamide or fludarabine, and
antithymocyte globulin. The cumulative incidence (CI) of myeloid engraftment was
90% [95% confidence interval (C.I.), 74-98%] with a median of 18 d (range, 10
48). CI of acute graft-versus-host disease (GvHD) grades II-IV was 30% (95% C.I.,
17-44%), while the incidence of chronic GVHD was 42% (95% C.I., 23-77%). The non
relapse mortality (NRM) at 100 d and 4 yr was 30% (95% C.I., 13-46%) and 47% (95%
C.I., 29-65%), respectively. EBV-related post-transplant lymphoproliferative
disease (EBV-PTLD) accounted for more than one-third of transplant-related death,
with an estimate incidence of 26% (95% C.I., 9-44). The incidence of relapse at 4
yr was 25% (95% C.I., 9-42%). Four-year event-free survival (EFS) and overall
survival (OS) were 28% and 30%, respectively. Despite a high NRM and an
unexpected high incidence of EBV-PTLD, UCBT in heavily pretreated HD patients is
an option for patients lacking a suitable adult donor, provided the disease is
not in refractory relapse.
PMID- 25845983
TI - Does kindness matter? Self-compassion buffers the negative impact of diabetes
distress on HbA1c.
AB - BACKGROUND: Higher self-compassion is associated with mental and physical health
benefits in both healthy and chronically ill populations. The current study
investigated the role of self-compassion in predicting depression, diabetes
specific distress and HbA1c in patients with diabetes. AIMS: To assess the
specific operationalization of negative emotionality that best predicted HbA1c
and to test whether self-compassion would buffer HbA1c in patients with diabetes
against the negative effects of distress. METHODS: Patients with diabetes (n =
110) completed measures assessing trait self-compassion, depression and diabetes
distress. HbA1c results were obtained through medical records. RESULTS: As
expected, diabetes-specific distress was a better predictor of HbA1c than
depression; self-compassion moderated the relationship between distress and HbA1c
such that higher distress predicted higher HbA1c at lower levels of self
compassion, but not at higher levels of self-compassion. CONCLUSIONS: In addition
to further demonstrating the link between distress and metabolic outcomes, these
findings suggest that self-compassion might buffer patients from the negative
metabolic consequences of diabetes-distress.
PMID- 25845985
TI - Exposure misclassification due to residential mobility during pregnancy.
AB - OBJECTIVES: Pregnant women are a highly mobile group, yet studies suggest
exposure error due to migration in pregnancy is minimal. We aimed to investigate
the impact of maternal residential mobility on exposure to environmental
variables (urban fabric, roads and air pollution (PM10 and NO2)) and socio
economic factors (deprivation) that varied spatially and temporally. METHODS: We
used data on residential histories for deliveries at >= 24 weeks gestation
recorded by the Northern Congenital Abnormality Survey, 2000-2008 (n=5399) to
compare: (a) exposure at conception assigned to maternal postcode at delivery
versus maternal postcode at conception, and (b) exposure at conception assigned
to maternal postcode at delivery versus mean exposure based on residences
throughout pregnancy. RESULTS: In this population, 24.4% of women moved during
pregnancy. Depending on the exposure variable assessed, 1-12% of women overall
were assigned an exposure at delivery >1 SD different to that at conception, and
2-25% assigned an exposure at delivery >1 SD different to the mean exposure
throughout pregnancy. CONCLUSIONS: To meaningfully explore the subtle
associations between environmental exposures and health, consideration must be
given to error introduced by residential mobility.
PMID- 25845984
TI - Urinary arsenic and insulin resistance in US adolescents.
AB - Chronic arsenic exposure has been associated with increased diabetes risk in
adults. Insulin resistance (IR) has been proposed as a mechanism of arsenic
related diabetes. Although limited evidence in adults found no association
between arsenic and IR, the association in adolescents is largely unknown. We
examined the association between urinary arsenic and insulin resistance in US
adolescents. Eight hundred thirty five adolescents aged 12-19 years, with
complete data on urinary arsenic (total arsenic, inorganic arsenic and
dimethylarsenic acid (DMA)), fasting glucose, insulin and key covariates were
identified from the National Health and Nutrition Examination Survey (NHANES)
cycles 2003/2004 through 2009/2010. Generalized additive mixed models accounting
for intra-cluster correlation arising from the complex survey design were used to
estimate the association between the updated Homeostasis Model Assessment (HOMA2)
IR and each type of arsenic. After adjusting for potential confounders, including
urinary creatinine, sociodemographic factors, BMI, waist circumference, and
arsenobetaine, arsenic exposure was not associated with HOMA2-IR. Interquartile
range increases in total arsenic, inorganic arsenic and DMA were associated with
1.5% (95% CI: -2.0, 5.2), 1.1% (95% CI: -1.5, 3.8) and 0.25% (95% CI: -2.3, 2.9)
increases in HOMA2-IR, respectively. In conclusion, despite arsenic's association
with diabetes in adults and potential role in insulin resistance, our findings do
not support the hypothesis that arsenic exposure at levels common in the US
contributes to insulin resistance in adolescents. Whether higher doses and longer
exposure duration are required for appreciable influence on insulin resistance,
or that arsenic does not act through insulin resistance to induce diabetes needs
further investigation.
PMID- 25845986
TI - Childhood asthma and spirometric indices are associated with polymorphic markers
of two vitamin D 25-hydroxylase genes.
AB - BACKGROUND: Polymorphic markers of vitamin D pathway genes have been associated
with asthma traits in different White populations. This study investigated the
relationship between asthma phenotypes and single nucleotide polymorphisms (SNPs)
of vitamin D receptor (VDR), vitamin D binding protein (GC), two 25-hydroxylases
(CYP2R1 and CYP27A1), and 1alpha-hydroxylase (CYP27B1) in Hong Kong Chinese
children. METHODS: 23 SNPs of the five vitamin D pathway genes were successfully
genotyped in 914 asthmatic children and 1231 non-allergic controls. Genotypic and
haplotypic associations with asthma phenotypes (diagnosis, spirometric indices,
total IgE, and eosinophil percentage) were analyzed by multivariate regression.
Generalized multifactor dimensionality reduction was used to detect epistatic
interactions between SNPs for asthma phenotypes. RESULTS: Several SNPs of
CYP27A1, CYP27B1, GC, and CYP2R1 were associated with asthma or spirometric
indices, although only the association between FEV1 and CYP2R1 rs7935792 passed
Bonferroni correction (p = 2.73 * 10(-4) ). Patients with CC genotype of
rs7935792 had higher FEV1 than those with the other two genotypes. Asthma was
also associated with TT haplotype of CYP27A1 and AGGATA haplotype of CYP2R1 (p =
0.021 and 0.024, respectively). Besides, strong association was found between
FEV1 and GATAG of CYP2R1 (beta = 13.37, p = 4.83 * 10(-4) ). GMDR failed to
identify any 2-locus to 4-locus interaction that modulated asthma or spirometric
indices. CONCLUSIONS: Several SNPs and haplotypes of CYP2R1 are associated with
asthma diagnosis and FEV1 in children. Asthma is also modestly associated with a
CYP27A1 haplotype. These two 25-hydroxylase genes may be genetic determinants for
asthma phenotypes in children.
PMID- 25845987
TI - Pregnancy-associated plasma protein A for prediction of fetal growth restriction.
PMID- 25845989
TI - Designing versatile heterogeneous catalysts based on Ag and Au nanoparticles
decorated on chitosan functionalized graphene oxide.
AB - Herein we report the covalent grafting of chitosan on graphene oxide (GO)
followed by a simple approach for anchoring silver (AgNPs) and gold (AuNPs)
nanoparticles onto a chitosan grafted graphene oxide surface by a NaBH4 reduction
method. Catalytic activity of prepared heterogeneous GO grafted chitosan
stabilized silver and gold nanocatalysts (GO-Chit-Ag/AuNPs) was explored for the
reduction of aromatic nitroarenes and degradation of hazardous azo dyes in the
presence of NaBH4. Both catalysts were found to exhibit excellent catalytic
activity towards the reduction of aromatic nitroarenes and azo dyes degradation.
Furthermore, the nanocatalysts were found to be selective towards the reduction
of nitro groups in halonitroarenes without any dehalogenation under mild
conditions.
PMID- 25845988
TI - Living Composites of Bacteria and Polymers as Biomimetic Films for Metal
Sequestration and Bioremediation.
AB - Herein, we report on composite materials of biologically active microorganisms
placed in a synthetic polymer matrix. These so-called "living composites" were
utilized for gold sequestration (Micrococcus luteus) and bioremediation of
nitrite (Nitrobacter winogradskyi) to demonstrate functionality. For the
preparation of the living composites the bacteria were first encased in a water
soluble polymer fiber (poly(vinyl alcohol), PVA) followed by coating the fibers
with a shell of hydrophobic poly(p-xylylene) (PPX) by chemical vapor deposition
(CVD). The combination of bacteria with polymer materials assured the stability
and biologically activity of the bacteria in an aqueous environment for several
weeks.
PMID- 25845990
TI - The safety and efficacy of single-agent pemetrexed in platinum-resistant advanced
urothelial carcinoma: a large single-institution experience.
AB - BACKGROUND: Pemetrexed is a commonly used treatment for platinum-resistant
advanced urothelial carcinoma (UC) based on objective response rates of 8% and
28% in two small phase II studies. To address the discrepancy in reported
response rates and to assess efficacy and toxicity outside of a clinical trial
setting, we performed a large retrospective analysis of pemetrexed use at
Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic
factors for overall survival in this setting to explore whether the neutrophil
lymphocyte ratio (NLR) had independent prognostic significance. PATIENTS AND
METHODS: Patients receiving pemetrexed for platinum-resistant advanced UC between
2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors
(RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox
regression analyses were used to examine the association of various factors with
efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities
were recorded. RESULTS: One hundred and twenty-nine patients were treated with
pemetrexed. The objective response rate was 5% (95% confidence interval: 1%-9%),
and the median duration of response was 8 months. Median progression-free
survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no
significant difference in response rate by age, Eastern Cooperative Oncology
Group (ECOG) performance status, or number of prior therapies. On multivariable
analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR
(p < .01) had independent prognostic significance for overall survival.
CONCLUSION: This 129-patient series is the largest reported data set describing
pemetrexed use in advanced UC. Activity was modest, although discovery of
molecular biomarkers predictive of response would be valuable to identify the
small subset of patients who do gain significant benefit. Overall, the data
highlight the urgent need to develop novel therapies for these patients.
PMID- 25845991
TI - Salvage systemic therapy for advanced urothelial carcinoma: on the cusp of a sea
change?
PMID- 25845992
TI - nab-Paclitaxel in Combination With Weekly Carboplatin With Concurrent
Radiotherapy in Stage III Non-Small Cell Lung Cancer.
AB - LESSONS LEARNED: The concomitant use of weekly nab-paclitaxel and carboplatin
with concurrent radiotherapy was demonstrated to be a safe therapeutic approach
in this phase I trial of 10 evaluable patients with stage III NSCLC.Despite the
lack of systemic glucocorticoids, there were no reported infusion reactions or
cases of peripheral neuropathy in this trial, both of which are known to occur
with the use of paclitaxel. BACKGROUND: Unresectable stage III non-small cell
lung cancer (NSCLC) has a 5-year survival rate of 20%, and concurrent
chemoradiotherapy results in significant toxicity with the use of current
chemotherapeutic agents. nab-Paclitaxel was approved by the U.S. Food and Drug
Administration in October 2012 for use along with carboplatin in advanced NSCLC.
This study was undertaken to determine the maximum tolerated dose and dose
limiting toxicities (DLTs) of weekly nab-paclitaxel given in combination with
carboplatin and concurrent radiotherapy in patients with unresectable stage III
NSCLC. METHODS: Escalating doses of once-weekly nab-paclitaxel were given along
with once-weekly carboplatin area under the plasma concentration time curve (AUC)
of 2 and concurrent radiotherapy 66 Gy in 33 fractions, followed by 2 cycles of
carboplatin and nab-paclitaxel consolidation chemotherapy. RESULTS: Eleven
patients were enrolled and received treatment per protocol, with 10 evaluable for
efficacy and toxicity. At dose level 1 (nab-paclitaxel 60 mg/m(2)), 2 DLTs were
observed: esophagitis and radiation dermatitis. Six patients were enrolled at
dose level 0 (nab-paclitaxel 40 mg/m(2)) with no DLTs. Nine of 10 evaluable
patients had a partial response. CONCLUSION: Concurrent chemoradiotherapy with
nab-paclitaxel 40 mg/m(2) and carboplatin AUC 2 is a safe and well-tolerated
therapeutic regimen in patients with stage III NSCLC. A separate phase I/II study
to evaluate the efficacy of this regimen is under way.
PMID- 25845993
TI - Effects of Fusarium mycotoxins in rations with different concentrate proportions
on serum haptoglobin and hepatocellular integrity in lactating dairy cows.
AB - It was hypothesized that long-term intake of a diet contaminated with
deoxynivalenol (DON) and differing in the proportion of concentrate might affect
hepatocellular integrity and function as well as biomarkers of systemic
inflammation in lactating dairy cows. In Period 1 (11 weeks), 26 lactating German
Holstein cows (13 primiparous and 13 pluriparous, 31 days in milk, 522 kg body
weight, on average) were divided into two groups and fed diets (50% concentrate)
with (MYC, n = 12; on average 5.3 mg DON/kg DM) or without (CON, n = 14) DON
contaminations. In Period 2 (16 weeks), each group was further divided into two
groups to test whether elevated concentrate proportion as additional burden might
enhance the toxicity of DON. The cows in MYC60 (n = 6; 4.6 mg DON/kg DM) and
CON60 (n = 7) received the diet with 60% concentrate, while cows in MYC30 (n = 6;
4.4 mg DON/kg DM) and CON30 (n = 7) received the diet with 30% concentrate. Blood
samples were taken in biweekly intervals for activities of aspartate amino
transferase (AST), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase
as well as for concentration of total bilirubin and haptoglobin. Biopsies from
liver were collected in week 27 for morphological analyses. No DON effect was
found for the variables assessed in blood. The diet with 60% concentrate led to
higher activities of AST and GLDH in Period 2. No morphological change was found
by both light and electron microscopic analyses of liver samples. Results
indicated that long-term intake of DON-contaminated diet over 27 weeks led to
neither relevant damages of hepatocytes nor systemic inflammatory responses in
lactating dairy cows, even if the dietary concentrate proportion was increased to
60%.
PMID- 25845994
TI - Matters of fiber size and myonuclear domain: Does size matter more than age?
AB - INTRODUCTION: The relationship between fiber size and myonuclear content is
poorly understood. METHODS: Biopsy cross-sections from young and old trained and
untrained healthy individuals were analyzed for fiber area and myonuclei, and 2
fiber-size-dependent cluster analyses were performed. RESULTS: When comparing
fibers of similar size, no effect of training or age was found for myonuclear
domain. There was a linear relationship between fiber area and myonuclei per
fiber (r = 0.99; P < 0.001) and a non-linear relationship between fiber area and
domain (r = 0.97-0.99; P < 0.0001), with a markedly smaller domain in fibers
<3,000 um(2). A higher proportion of type II fibers <3,000 um(2) was observed in
the old subjects. CONCLUSIONS: These findings suggest that age-related reductions
in myonuclear domain size could be explained by the greater proportion of small
fibers. The data also highlight the usefulness of determining fiber-size-based
clusters for gaining mechanistic insight into the relationship between skeletal
muscle fiber size and myonuclear content.
PMID- 25845995
TI - Evaluating nonindigenous species management in a Bayesian networks derived
relative risk framework for Padilla Bay, WA, USA.
AB - Many coastal regions are encountering issues with the spread of nonindigenous
species (NIS). In this study, we conducted a regional risk assessment using a
Bayesian network relative risk model (BN-RRM) to analyze multiple vectors of NIS
introductions to Padilla Bay, Washington, a National Estuarine Research Reserve.
We had 3 objectives in this study. The 1st objective was to determine whether the
BN-RRM could be used to calculate risk from NIS introductions for Padilla Bay.
Our 2nd objective was to determine which regions and endpoints were at greatest
risk from NIS introductions. Our 3rd objective was to incorporate a management
option into the model and predict endpoint risk if it were to be implemented.
Eradication can occur at different stages of NIS invasions, such as the
elimination of these species before being introduced to the habitat or removal of
the species after settlement. We incorporated the ballast water treatment
management scenario into the model, observed the risk to the endpoints, and
compared this risk with the initial risk estimates. The model results indicated
that the southern portion of the bay was at greatest risk because of NIS. Changes
in community composition, Dungeness crab, and eelgrass were the endpoints most at
risk from NIS introductions. The currents node, which controls the exposure of
NIS to the bay from the surrounding marine environment, was the parameter that
had the greatest influence on risk. The ballast water management scenario
displayed an approximate 1% reduction in risk in this Padilla Bay case study. The
models we developed provide an adaptable template for decision makers interested
in managing NIS in other coastal regions and large bodies of water.
PMID- 25845996
TI - Inherent organic compounds in biochar--Their content, composition and potential
toxic effects.
AB - Pyrolysis liquids consist of thermal degradation products of biomass in various
stages of its decomposition. Therefore, if biochar gets affected by re-condensed
pyrolysis liquids it is likely to contain a huge variety of organic compounds. In
this study the chemical composition of such compounds associated with two
contaminated, high-volatile organic compound (VOC) biochars were investigated and
compared with those for a low-VOC biochar. The water-soluble organic compounds
with the highest concentrations in the two high-VOC biochars were acetic, formic,
butyric and propionic acids; methanol, phenol, o-, m- and p-cresol, and 2,4
dimethylphenol, all with concentrations over 100 MUg g(-1). The concentrations of
16 US EPA PAHs determined by 36 h toluene extractions were 6.09 MUg g(-1) for the
low-VOC biochar. For high-VOC biochar the total concentrations were 53.42 MUg g(
1) and 27.89 MUg g(-1), while concentrations of water-soluble PAHs ranged from
1.5 to 2 MUg g(-1). Despite the concentrations of PAHs exceeding biochar
guideline values, it was concluded that, for these particular biochars, the
biggest concern for application to soil would be the co-occurrence of VOCs such
as low molecular weight (LMW) organic acids and phenols, as these can be highly
mobile and have a high potential to cause phytotoxic effects. Therefore, based on
results of this study we strongly suggest for VOCs to be included among criteria
for assessment of biochar quality.
PMID- 25845997
TI - Dissolved organic matter removal during coal slag additive soil aquifer treatment
for secondary effluent recharging: Contribution of aerobic biodegradation.
AB - Recycling wastewater treatment plant (WWTP) effluent at low cost via the soil
aquifer treatment (SAT), which has been considered as a renewable approach in
regenerating potable and non-potable water, is welcome in arid and semi-arid
regions throughout the world. In this study, the effect of a coal slag additive
on the bulk removal of the dissolved organic matter (DOM) in WWTP effluent during
SAT operation was explored via the matrix configurations of both coal slag layer
and natural soil layer. Azide inhibition and XAD-resins fractionation experiments
indicated that the appropriate configuration designing of an upper soil layer (25
cm) and a mixture of soil/coal slag underneath would enhance the removal
efficiency of adsorption and anaerobic biodegradation to the same level as that
of aerobic biodegradation (31.7% vs 32.2%), while it was only 29.4% compared with
the aerobic biodegradation during traditional 50 cm soil column operation. The
added coal slag would preferentially adsorb the hydrophobic DOM, and those
adsorbed organics could be partially biodegraded by the biomass within the SAT
systems. Compared with the relatively lower dissolved organic carbon (DOC),
ultraviolet light adsorption at 254 nm (UV-254) and trihalomethane formation
potential (THMFP) removal rate of the original soil column (42.0%, 32.9%, and
28.0%, respectively), SSL2 and SSL4 columns would enhance the bulk removal
efficiency to more than 60%. Moreover, a coal slag additive in the SAT columns
could decline the aromatic components (fulvic-like organics and tryptophan-like
proteins) significantly.
PMID- 25845998
TI - Effect of weathering transformations of coal combustion residuals on trace
elements mobility in view of the environmental safety and sustainability of their
disposal and use. II. Element release.
AB - This paper is the second one of two companion papers. It presents results of a
study aimed at assessing the effect of real time weathering transformations of
Coal Combustion Residuals (CCRs) on trace element binding/release and its
environmental implications. The study is based on the chemical composition of
pore solutions extracted from primary alkaline Class F CCRs, 0 to >40 years old,
sampled from the surface layer and vertical profiles at four selected typical
CCRs impoundments. The long-term weathering transformations were found to lead to
gradual acidification to pH < 4 of this primary alkaline material, due to
internal processes of mineral formation/dissolution. Direct analysis of the pore
solutions and a statistical analysis have shown different susceptibility of many
trace elements to release during internal acidification processes occurring at
consecutive Wash-out I (pH > 8), Dissolution II (8 >= pH >= 7) and Delayed
Release III (pH < 7) stages of weathering compared to that at external sources of
pH. The elements occurring in the CCRs are represented by three major groups
showing the highest release to pore water: (a) within the acidic pH range (Na, K,
Zn, Fe, Cd, Mo, Cr, B, Mn, Be and Ni; (b) within the near-neutral pH range (Al,
V, Ba, Cu and Ag) and also Sb, Hg and Co not analyzed at pH < 7; (c) within the
alkaline pH range (Ca, Mg, Pb, As, Se, Tl). Elements whose concentrations
exceeded the threshold values for good chemical status of groundwater (TVs) at
all weathering stages over the entire pH range studied were K, Al, B, Cr, Mo, V,
As, Se, Sb and Hg, while Na, Zn, Fe and Cd showed particularly high delayed
release at pH < 7, thus confirming the need of a precautionary approach to CCRs
uncontrolled disposal and bulk reuse as common fill in view of long term
environmental safety and sustainability.
PMID- 25845999
TI - Central sorting and recovery of MSW recyclable materials: A review of
technological state-of-the-art, cases, practice and implications for materials
recycling.
AB - Today's waste regulation in the EU comprises stringent material recovery targets
and calls for comprehensive programs in order to achieve them. A similar movement
is seen in the US where more and more states and communities commit to high
diversion rates from landfills. The present paper reviews scientific literature,
case studies and results from pilot projects, on the topic of central sorting of
recyclable materials commonly found in waste from households. The study
contributes, inter alia, with background understanding on the development of
materials recovery, both in a historical and geographical perspective. Physical
processing and sorting technology has reached a high level of maturity, and many
quality issues linked to cross-contamination by commingling have been
successfully addressed to date. New sorting plants tend to benefit from economies
of scale, and innovations in automation and process control, which are targeted
at curtailing process inefficiencies shown by operational practice. Technology
developed for the sorting of commingled recyclables from separate collection is
also being successfully used to upgrade residual MSW processing plants. The
strongest motivation for central sorting of residual MSW is found for areas where
source separation and separate collection is difficult, such as urban
agglomerations, and can in such areas contribute to increasing recycling rates,
either complementary to- or as a substitute for source separation of certain
materials, such as plastics and metals.
PMID- 25846000
TI - Modeling, kinetic, and equilibrium characterization of paraquat adsorption onto
polyurethane foam using the ion-pairing technique.
AB - We studied the adsorption of paraquat onto polyurethane foam (PUF) when it was in
a medium containing sodium dodecylsulfate (SDS). The adsorption efficiency was
dependent on the concentration of SDS in solution, because the formation of an
ion-associate between the cationic paraquat and the dodecylsulfate anion was
found to be a fundamental step in the process. A computational study was carried
out to identify the possible structure of the ion-associate in aqueous medium.
The obtained data demonstrated that the structure is probably formed from four
units of dodecylsulfate bonded to one paraquat moiety. The results showed that
94% of the paraquat present in 45 mL of a solution containing 3.90 * 10(-5) mol
L(-1) could be retained by 300 mg of PUF, resulting in the removal of 2.20 mg of
paraquat. The experimental data were reasonably adjusted to the Freundlich
isotherm and to the pseudo-second-order kinetic model. Also, the application of
Morris-Weber and Reichenberg models indicated that both film-diffusion and
intraparticle-diffusion processes were active during the control of the
adsorption kinetics.
PMID- 25846001
TI - Valuing the commons: An international study on the recreational benefits of the
Baltic Sea.
AB - The Baltic Sea provides benefits to all of the nine nations along its coastline,
with some 85 million people living within the catchment area. Achieving
improvements in water quality requires international cooperation. The likelihood
of effective cooperation is known to depend on the distribution across countries
of the benefits and costs of actions needed to improve water quality. In this
paper, we estimate the benefits associated with recreational use of the Baltic
Sea in current environmental conditions using a travel cost approach, based on
data from a large, standardized survey of households in each of the 9 Baltic Sea
states. Both the probability of engaging in recreation (participation) and the
number of visits people make are modeled. A large variation in the number of
trips and the extent of participation is found, along with large differences in
current annual economic benefits from Baltic Sea recreation. The total annual
recreation benefits are close to 15 billion EUR. Under a water quality
improvement scenario, the proportional increases in benefits range from 7 to 18%
of the current annual benefits across countries. Depending on how the costs of
actions are distributed, this could imply difficulties in achieving more
international cooperation to achieve such improvements.
PMID- 25846002
TI - CO2 sequestration using accelerated gas-solid carbonation of pre-treated EAF
steel-making bag house dust.
AB - Mineral CO2 sequestration is a promising process for the reduction of carbon
dioxide emissions to the atmosphere. In this paper, alkaline calcium-rich dust
particles collected from bag filters of electric arc furnaces (EAF) for steel
making were utilized as a viable raw material for mineral CO2 sequestration. The
dust particles were pre-treated through hydration, drying and screening. The pre
treated particles were then subjected to direct gas-solid carbonation reaction in
a fluidized-bed reactor. The carbonated products were characterized to determine
the overall sequestration capacity and the mineralogical structures. Leaching
tests were also performed to measure the extracted minerals from the carbonated
dust and evaluate the carbonation process on dust stabilization. The experimental
results indicated that CO2 could be sequestered using the pre-treated bag house
dust. The maximum sequestration of CO2 was 0.657 kg/kg of dust, based on the
total calcium content. The highest degree of carbonation achieved was 42.5% and
the carbonation efficiency was 69% at room temperature.
PMID- 25846003
TI - Hydrotalcite-TiO2 magnetic iron oxide intercalated with the anionic surfactant
dodecylsulfate in the photocatalytic degradation of methylene blue dye.
AB - The new magnetic photocatalysts HT/TiO2/Fe and HT-DS/TiO2/Fe, modified with the
anionic surfactant sodium dodecylsulfate (DS) were successfully synthesized in
this work. Titanium dioxide (anatase) followed by iron oxide were deposited on
the hydrotalcite support. Several catalyst samples were prepared with different
amounts of titanium and iron. The photocatalysts were characterized by infrared
and Raman spectroscopy, X-ray diffraction, scanning electron microscopy.
Photocatalytic performance was analyzed by UV-visible radiation (filter cutoff,
lambda > 300 nm) of an aqueous solution (24 mg/L) of methylene blue (MB). The
most efficient catalyst was obtained at an iron oxide:TiO2 molar ratio of 2:3.
This catalyst showed high photocatalytic activity, removing 96% of the color and
61% of total organic carbon from the MB solution after 120 min. It was easily
removed from solution after use because of its magnetic properties. The reuse of
the HT-DS/TiO2/Fe23 catalyst was viable and the catalyst was structurally stable
for at least four consecutive photocatalytic cycles.
PMID- 25846004
TI - Protective activity of carnosine and anserine against zinc-induced neurotoxicity:
a possible treatment for vascular dementia.
AB - Carnosine (beta-alanyl-L-histidine) is a small dipeptide with numerous beneficial
effects, including the maintenance of the acid-base balance, antioxidant
properties, chelating agent, anti-crosslinking, and anti-glycation activities.
High levels of carnosine and its analogue anserine (1-methyl carnosine) are found
in skeletal muscle and the brain. Zinc (Zn)-induced neurotoxicity plays a crucial
role in the pathogenesis of vascular dementia (VD), and carnosine inhibits Zn
induced neuronal death. Here, the protective activity of carnosine against Zn
induced neurotoxicity and its molecular mechanisms such as cellular Zn influx and
Zn-induced gene expression were investigated using immortalised hypothalamic
neurons (GT1-7 cells). Carnosine and anserine protected against Zn-induced
neurotoxicity not by preventing increases in intracellular Zn(2+) but by
participating in the regulation of the endoplasmic reticulum (ER) stress pathway
and the activity-regulated cytoskeletal protein (Arc). Accordingly, carnosine and
anserine protected against neurotoxicity induced by ER-stress inducers
thapsigargin and tunicamycin. Hence, carnosine and anserine are expected to have
future therapeutic potential for VD and other neurodegenerative diseases.
PMID- 25846005
TI - Structural analysis of the polo-box domain of human Polo-like kinase 2.
AB - Polo-like kinases (Plks) are the key regulators of cell cycle progression, the
members of which share a kinase domain and a polo-box domain (PBD) that serves as
a protein-binding module. While Plk1 is a promising target for antitumor therapy,
Plk2 is regarded as a tumor suppressor even though the two Plks commonly
recognize the S-pS/T-P motif through their PBD. Herein, we report the crystal
structure of the PBD of Plk2 at 2.7 A. Despite the overall structural similarity
with that of Plk1 reflecting their high sequence homology, the crystal structure
also contains its own features including the highly ordered loop connecting two
subdomains and the absence of 310 -helices in the N-terminal region unlike the
PBD of Plk1. Based on the three-dimensional structure, we furthermore could model
its interaction with two types of phosphopeptides, one of which was previously
screened as the optimal peptide for the PBD of Plk2.
PMID- 25846006
TI - AMPK Activation Affects Glutamate Metabolism in Astrocytes.
AB - Mammalian AMP-activated protein kinase (AMPK) functions as a metabolic switch. It
is composed of 3 different subunits and its activation depends on phosphorylation
of a threonine residue (Thr172) in the alpha-subunit. This phosphorylation can be
brought about by 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR)
which in the cells is converted to a monophosphorylated nucleotide mimicking the
effect of AMP. We show that the preparation of cultured astrocytes used for
metabolic studies expresses AMPK, which could be phosphorylated by exposure of
the cells to AICAR. The effect of AMPK activation on glutamate metabolism in
astrocytes was studied using primary cultures of these cells from mouse cerebral
cortex during incubation in media containing 2.5 mM glucose and 100 uM [U
(13)C]glutamate. The metabolism of glutamate including a detailed analysis of its
metabolic pathways involving the tricarboxylic acid (TCA) cycle was studied using
high-performance liquid chromatography analysis supplemented with gas
chromatography-mass spectrometry technology. It was found that AMPK activation
had profound effects on the pathways involved in glutamate metabolism since the
entrance of the glutamate carbon skeleton into the TCA cycle was reduced. On the
other hand, glutamate uptake into the astrocytes as well as its conversion to
glutamine catalyzed by glutamine synthetase was not affected by AMPK activation.
Interestingly, synthesis and release of citrate, which are hallmarks of
astrocytic function, were affected by a reduction of the flux of glutamate
derived carbon through the malic enzyme and pyruvate carboxylase catalyzed
reactions. Finally, it was found that in the presence of glutamate as an
additional substrate, glucose metabolism monitored by the use of tritiated
deoxyglucose was unaffected by AMPK activation. Accordingly, the effects of AMPK
activation appeared to be specific for certain key processes involved in
glutamate metabolism.
PMID- 25846007
TI - mTOR and Erk1/2 Signaling in the Cerebrospinal Fluid-Contacting Nucleus is
Involved in Neuropathic Pain.
AB - The cerebrospinal fluid-contacting nucleus (CSF-CN) has been demonstrated to be
involved in neuropathic pain, but the underlying molecular mechanisms remain
unclear. Previous work has shown that mTOR and ERK1/2 are important signaling
pathways regulating neuropathic pain. However, studies on the interactions
between these major pathways in neuropathic pain are very rare. Therefore, the
purpose of this study is to determine whether mTOR and ERK1/2 exist in the CSF-CN
and elucidate their alterations in neuropathic pain, especially, the crosstalk
between them. Our results showed that mTOR and ERK1/2 were distributed in the CSF
CN, and their expression levels were increased in chronic constriction injury
(CCI)-induced neuropathic pain. Furthermore, the injection of both the mTOR
antagonist rapamycin and the ERK1/2 antagonist U0126 into the lateral ventricle
of the brain attenuated CCI-induced neuropathic pain. Inhibition of the ERK1/2
pathway had little impact on mTOR signaling, but inhibition of the mTOR pathway
significantly increased ERK/2 signaling. The coadministration of rapamycin and
U0126 inhibited the rapamycin-induced upregulation of ERK, and had a greater
effect on pain behaviors than did the single-drug administrations. These data
extend our understanding of the relationship between mTOR and ERK in the
supraspinal site and demonstrate that the CSF-CN participates in neuropathic pain
via the regulation of mTOR and ERK1/2.
PMID- 25846008
TI - Activation of mGluR5 Attenuates Microglial Activation and Neuronal Apoptosis in
Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats.
AB - Activation of metabotropic glutamate receptor 5 (mGluR5) provided neuroprotection
in multiple central nervous system injury, but the roles of mGluR5 in
subarachnoid hemorrhage (SAH) remain unclear. In present study, we aimed to
evaluate whether activation of mGluR5 attenuates early brain injury (EBI) after
experimental SAH in rats. We found that selective mGluR5 orthosteric agonist CHPG
or positive allosteric modulator VU0360172 administration significantly improves
neurological function and attenuates brain edema at 24 h after SAH. Furthermore,
mGluR5 obviously expresses in activated microglia (ED-1 positive) after SAH. CHPG
or VU0360172 administration significantly reduces the numbers of activated
microglia and the protein and mRNA levels of pro-inflammatory cytokines IL-1beta,
IL-6 and TNF-alpha at 24 h after SAH. Moreover, CHPG or VU0360172 administration
obviously reduces the number of TUNEL-positive cells and active caspase-3/NeuN
positive neurons in cortex at 24 h after SAH. CHPG or VU0360172 administration
significantly up-regulates the expression of Bcl-2, and down-regulates the
expression of Bax and active caspase-3, which in turn increases the ratio of Bcl
2/Bax. Our results indicate that activation of mGluR5 attenuates microglial
activation and neuronal apoptosis, and improves neurological function in EBI
after SAH.
PMID- 25846009
TI - Synthesis and Evaluation of New 4-Chloro-2-(3-chloro-4-fluorophenyl)-5
(aliphatic/cyclic saturated amino)pyridazin-3(2H)-one Derivatives as Anticancer,
Antiangiogenic, and Antioxidant Agents.
AB - Pyridazinones are widely recognized as versatile scaffolds with a wide spectrum
of biological activities. In the present work, a series of new 4-chloro-2-(3
chloro-4-fluorophenyl)-5-(aliphatic/cyclic saturated amino)pyridazin-3(2H)-one
derivatives 4a-i were synthesized and characterized by spectral techniques. The
inhibitory effects of the synthesized compounds 4a-i on the viability of three
human cancer cell lines, HEP3BPN 11 (liver), MDA 453 (breast), and HL 60
(leukemia), were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) reduction assay. Among the compounds 4a-i
screened, 4g and 4i exhibited inhibitory activity very close to the standard
methotrexate; therefore, these lead compounds were further tested for their
potential to inhibit the proangiogenic cytokines involved in tumor progression.
Compound 4g was found to be a potent antiangiogenic agent against TNFalpha, VEGF,
FGFb, and TGFbeta, whereas 4i showed potent antiangiogenic activity against
TNFalpha, VEGF, FGFb, and leptin. All the compounds 4a-i were screened for their
antioxidant activities using 2,2-diphenyl-1-picryl hydrazine (DPPH), OH, and
superoxide anion radicals. Compound 4f showed better OH radical scavenging
activity than the standard ascorbic acid.
PMID- 25846010
TI - Stressful life events preceding the onset of depression in Asian patients with
major depressive disorder.
AB - BACKGROUND: Previous studies have identified the significant role of stressful
life events in the onset of depressive episodes. However, there is a paucity of
cross-national studies on stressful life events that precede depression. AIMS: We
aimed to compare types of stressful life events associated with the onset of
depressive episodes in patients with major depressive disorder (MDD) in five
Asian countries. METHOD: A total of 507 outpatients with MDD were recruited in
China (n = 114), South Korea (n = 101), Malaysia (n = 90), Thailand (n = 103) and
Taiwan (n = 99). All patients were assessed with the Mini-International
Neuropsychiatric Interview and the List of Threatening Experiences. The
prevalence of each type of stressful life events was calculated and compared
between each country. RESULTS: The type of stressful life event that preceded the
onset of a depressive episode differed between patients in China and Taiwan and
those in South Korea, Malaysia and Thailand. Patients in China and Taiwan were
less likely to report interpersonal relationship problems and
occupational/financial problems than patients in South Korea, Malaysia and
Thailand. CONCLUSION: Understanding the nature and basis of culturally determined
susceptibilities to specific stressful life events is critical for establishing a
policy of depression prevention and providing effective counseling services for
depressed patients.
PMID- 25846011
TI - A novel cisplatin mediated apoptosis pathway is associated with acid
sphingomyelinase and FAS proapoptotic protein activation in ovarian cancer.
AB - Platinum-based anticancer drugs, including cisplatin and carboplatin, have been
cornerstones in the treatment of solid tumors. We report here that these DNA
damaging agents, particularly cisplatin, induce apoptosis through plasma membrane
disruption, triggering FAS death receptor via mitochondrial (intrinsic) pathways.
Our objectives were to: quantify the composition of membrane metabolites; and
determine the potential involvement of acid sphingomyelinase (ASMase) in the FAS
mediated apoptosis in ovarian cancer after cisplatin treatment. The resulting
analysis revealed enhanced apoptosis as measured by: increased phosphocholine,
and glycerophosphocholine; elevated cellular energetics; and phosphocreatine and
nucleoside triphosphate concentrations. The plasma membrane alterations were
accompanied by increased ASMase activity, leading to the upregulation of FAS,
FASL and related pro-apoptotic BAX and PUMA genes. Moreover FAS, FASL, BAX, PUMA,
CASPASE-3 and -9 proteins were upregulated. Our findings implicate ASMase
activity and the intrinsic pathways in cisplatin-mediated membrane demise, and
contribute to our understanding of the mechanisms by which ovarian tumors may
become resistant to cisplatin.
PMID- 25846012
TI - No trade-off between high and low temperature tolerance in a winter acclimatized
Danish Drosophila subobscura population.
AB - Coping with cold winter conditions is a major challenge for many insects. In
early spring we observed newly emerged Drosophila subobscura, which had
overwintered as larvae and pupae. As temperatures increase during spring these
flies are faced with higher minimum and maximum temperatures in their natural
microhabitat. Thus, there is a potential costly mismatch between winter and early
spring acclimatization and the increased ambient temperatures later in adult
life. We obtained individuals from a natural Danish population of D. subobscura
and acclimated them in the laboratory to 20 degrees C for one generation, and
compared critical thermal maximum (CTmax) and minimum (CTmin) to that of
individuals collected directly from their natural microhabitat. The two
populations (laboratory and field) were subsequently both held in the laboratory
at 20 degrees C and tested for their CTmax and CTmin every third day for 28
days. At the first day of testing, field acclimatized D. subobscura had both
higher heat and cold resistance compared to laboratory flies, and thereby a
considerable larger thermal scope. Following transfer to the laboratory, cold and
heat resistance of the field flies decreased over time relative to the laboratory
flies. Despite the substantial decrease in thermal tolerances the thermal scope
remained larger for field acclimatized individuals for the duration of the
experiment. We conclude that flies acclimatized to their natural microhabitat had
increased cold resistance, without a loss in heat tolerance. Thus while a
negative correlation between cold and heat tolerance is typically observed in
laboratory studies in Drosophila sp., this was not observed for field
acclimatized D. subobscura in this study. We suggest that this is an adaptation
to juvenile overwintering in temperate cold environments, where developmental
(winter) temperatures can be much lower than temperatures experienced by
reproducing adults after emergence (spring). The ability to gain cold tolerance
through acclimatization without a parallel loss of heat tolerance affects thermal
scope and suggests that high and low thermal tolerance act through mechanisms
with different dynamics and reversibility.
PMID- 25846013
TI - Chill-tolerant Gryllus crickets maintain ion balance at low temperatures.
AB - Insect cold tolerance is both phenotypically-plastic and evolutionarily labile,
but the mechanisms underlying this variation are uncertain. Chill-susceptible
insects lose ion and water homeostasis in the cold, which contributes to the
development of injuries and eventually death. We thus hypothesized that more cold
tolerant insects will better maintain ion and water balance at low temperatures.
We used rapid cold-hardening (RCH) and cold acclimation to improve cold tolerance
of male Gryllus pennsylvanicus, and also compared this species to its cold
tolerant relative (Gryllus veletis). Cold acclimation and RCH decreased the
critical thermal minimum (CTmin) and chill coma recovery time (CCR) in G.
pennsylvanicus, but while cold acclimation improved survival of 0 degrees C, RCH
did not; G. veletis was consistently more cold-tolerant (and had lower CCR and
CTmin) than G. pennsylvanicus. During cold exposure, hemolymph water and Na(+)
migrated to the gut of warm-acclimated G. pennsylvanicus, which increased
hemolymph [K(+)] and decreased muscle K(+) equilibrium potentials. By contrast,
cold-acclimated G. pennsylvanicus suffered a smaller loss of ion and water
homeostasis during cold exposure, and this redistribution did not occur at all in
cold-exposed G. veletis. The loss of ion and water balance was similar between
RCH and warm-acclimated G. pennsylvanicus, suggesting that different mechanisms
underlie decreased CCR and CTmin compared to increased survival at 0 degrees C.
We conclude that increased tolerance of chilling is associated with improved
maintenance of ion and water homeostasis in the cold, and that this is consistent
for both phenotypic plasticity and evolved cold tolerance.
PMID- 25846014
TI - Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C
virus previously treated in clinical trials of sofosbuvir regimens.
AB - Patients who fail to achieve sustained virological response (SVR) after treatment
with sofosbuvir (SOF) plus ribavirin (RBV) with or without pegylated interferon
(Peg-IFN) do not have established retreatment options. We conducted an open-label
trial to assess the efficacy and safety of ledipasvir (LDV)-SOF plus RBV in
patients with genotype 1 hepatitis C virus (HCV) who did not achieve SVR after
treatment in phase II and III trials of SOF regimens. We enrolled 51 patients at
24 sites in the United States. All patients received the fixed-dose combination
tablet of LDV-SOF once-daily plus weight-based RBV (1,000 or 1,200 mg/day) for 12
weeks. The efficacy endpoint was the proportion of patients with SVR 12 weeks
after discontinuation of therapy (SVR12). Of the 51 patients enrolled, 25 (49%)
had previously received SOF plus Peg-IFN-RBV, 20 (39%) had received SOF-RBV, 5
(10%) had received SOF placebo plus Peg-IFN-RBV, and 1 (2%) received GS-0938
monotherapy. Fourteen (27%) had compensated cirrhosis at baseline, and 47 (92%)
had non-CC interleukin-28B genotypes. SVR12 was achieved by 50 of the 51 patients
(98%) treated. Among the 45 patients who received SOF in earlier treatment, 44
(98%) achieved SVR12. The only patient who did not achieve SVR12 was a patient
with genotype 3a HCV who had been incorrectly genotyped as 1a in the previous
study. Given the high rates of SVR12, no differences among patient subgroups were
discernible. Of 51 patients, 41 (80%) experienced at least one adverse event
(AE), but most events were mild to moderate in severity. The most common AEs were
fatigue, headache, and diarrhea. One patient discontinued treatment because of an
unrelated AE (bipolar disorder). CONCLUSION: Twelve weeks of LDV-SOF plus RBV was
an effective and safe treatment for patients who have not achieved SVR with
earlier regimens that included SOF.
PMID- 25846015
TI - A combined morphometric analysis of foot form and its association with sex,
stature, and body mass.
AB - OBJECTIVES: Morphometric analysis of footprints is a classic means for orthopedic
diagnosis. In forensics and physical anthropology, it is commonly used for the
estimation of stature and body mass. We studied individual variation and sexual
dimorphism of foot dimensions and footprint shape by a combination of classic
foot measurements and geometric morphometric methods. METHODS: Left and right
feet of 134 healthy adult males and females were scanned twice with a 3D optical
laser scanner, and stature as well as body mass were recorded. Foot length and
width were measured on the 3D scans. The 2D footprints were extracted as the
plantar-most 2 mm of the 3D scans and measured with 85 landmarks and
semilandmarks. RESULTS: Both foot size and footprint shape are sexually dimorphic
and relate to stature and body mass. While dimorphism in foot length largely
results from dimorphism in stature, dimorphism in footprint shape partly owes to
the dimorphism in BMI. Stature could be estimated well based on foot length (R(2)
= 0.76), whereas body mass was more closely related to foot width (R(2) =
0.62). Sex could be estimated correctly for 95% of the individuals based on a
combination of foot width and length. DISCUSSION: Geometric morphometrics proved
to be an effective tool for the detailed analysis of footprint shape. However,
for the estimation of stature, body mass, and sex, shape variables did not
considerably improve estimates based on foot length and width.
PMID- 25846016
TI - A person-centered approach to adolescent emotion regulation: Associations with
psychopathology and parenting.
AB - Adolescence is a unique period of heightened emotional arousal and still
developing regulatory abilities. Adolescent emotion regulation patterns may be
critically involved in adolescents' psychosocial development, but patterns of
emotion regulation in youths are not well understood. The current study used
latent profile analysis (LPA) to elucidate patterns of emotion expression,
experience, and emotion-related physiological arousal in adolescents. A sample of
198 adolescents and their primary caregivers participated in an emotionally
arousing parent-adolescent conflict interaction. Adolescents' observed emotion
expressions, emotion experiences, and heart rate (HR) and caregiver parenting
behaviors were assessed during and/or after the interaction. Parents reported on
adolescents' internalizing and externalizing symptoms, and youths reported on
depressive symptoms. The LPA revealed four emotion regulation profiles: a
moderate HR and high expression profile, a suppression profile (with low negative
emotion expression and high emotion experience), a low reactive profile, and a
high reactive profile. The moderate HR and high expression profile was associated
with lower conduct disorder symptoms, the suppression profile was related to
lower anxiety symptoms, and the high reactive profile was associated with higher
adolescent depressive symptoms. The high reactive profile and moderate HR and
high expression profile were associated with more negative/critical parenting
behaviors. Findings suggest that profiles of adolescent emotion regulation can be
empirically identified and may be significant risk factors for psychopathology.
PMID- 25846017
TI - Progressive outer retinal necrosis in immunocompromised kidney allograft
recipient.
AB - Ocular complications in patients who underwent renal transplantation are
attributed to side effects of the immunosuppressive regimen. Progressive outer
retinal necrosis (PORN) syndrome is a clinical variant of necrotizing herpetic
retinopathy and it occurs almost exclusively in patients with acquired
immunodeficiency syndrome. We present a case of a human immunodeficiency virus
negative patient who underwent renal transplant and, after a few years, developed
bilateral PORN associated with viral infections. Varicella zoster virus (VZV) and
BK virus were identified by polymerase chain reaction from the vitreous fluid. It
is unclear which of the viruses identified had the dominant role in the
pathogenesis of PORN and other organ damage, or whether their actions were
synergistic. Adequate antiviral immune surveillance, as well as pre-transplant
vaccination against VZV, may reduce the incidence of VZV infection and its
complications.
PMID- 25846018
TI - Mental health care use in relation to depressive symptoms among pregnant women in
the USA.
AB - We examined mental health care use in relation to depressive symptoms (Patient
Health Questionnaire (PHQ-9) >= 10) among a nationally representative sample of
pregnant women using data from the National Health and Nutrition Examination
Survey 2005-2012. Logistic regression models estimated crude and adjusted odds
ratios for mental health care use in the past year in relation to depressive
symptoms. While 8.2 % (95 % CI 4.6-11.8) of pregnant women were depressed, only
12 % (95 % CI 1.8-22.1) of these women reported mental health care use in the
past year.
PMID- 25846026
TI - Attenuation of Porphyromonas gingivalis oral infection by alpha-amylase and
pentamidine.
AB - The Porphyromonas gingivalis bacterium is one of the most influential pathogens
in oral infections. In the current study, the antimicrobial activity of alpha
amylase and pentamidine against Porphyromonas gingivalis was evaluated. Their in
vitro inhibitory activity was investigated with the agar overlay technique, and
the minimal inhibitory and bactericidal concentrations were determined. Using the
bactericidal concentration, the antimicrobial actions of the inhibitors were
investigated. In the present study, multiple techniques were utilized, including
scanning electron microscopy (SEM), general structural analysis and differential
gene expression analysis. The results obtained from SEM and bactericidal analysis
indicated a notable observation; the pentamidine and alpha-amylase treatment
destroyed the structure of the bacterial cell membranes, which led to cell death.
These results were used to further explore these inhibitors and the mechanisms by
which they act. Downregulated expression levels were observed for a number of
genes coding for hemagglutinins and gingipains, and various genes involved in
hemin uptake, chromosome replication and energy production. However, the
expression levels of genes associated with iron storage and oxidative stress were
upregulated by alpha-amylase and pentamidine. A greater effect was noted in
response to pentamidine treatment. The results of the present study demonstrate
promising therapeutic potential for alpha-amylases and pentamidine. These
molecules have the potential to be used to develop novel drugs and broaden the
availability of pharmacological tools for the attenuation of oral infections
caused by Porphyromonas gingivalis.
PMID- 25846027
TI - Re: Editorial Comment on Clinical Performance of Serum Isoform (-2)proPSA (p2PSA)
and its Derivatives, Namely %p2PSA and PHI (Prostate Health Index) in Men Younger
than 60 Years of Age: Results from a Multicentric European Study: S. S. Taneja J
Urol 2014;192:421.
PMID- 25846029
TI - Methodological challenges when performing a systematic review.
AB - Well-conducted systematic reviews can provide a foundation upon which to base
educational curricula, practice guidelines and healthcare policy. We aim to
provide an overview of important methodological issues that need to be addressed
during the five phases of performing a systematic review. 1. The specific
problems to be addressed by the systematic review need to be formulated as clear,
unambiguous and structured question/s. 2. Literature from multiple resources
should be searched to avoid publication biases, as positive outcomes are more
likely to be published than null/negative results. 3. The quality of selected
articles should be assessed using a checklist, while the reliability of graders,
as well as the quality of the checklist, needs to be established a priori. 4.
Statistical heterogeneity needs to be assessed to determine if a meta-analysis is
appropriate to pool the data. If not, a narrative synthesis of the
evidence/overall findings needs to be performed within a clinical context.
PMID- 25846030
TI - Binding proteins enhance specific uptake rate by increasing the substrate
transporter encounter rate.
AB - Microorganisms rely on binding-protein assisted, active transport systems to
scavenge for scarce nutrients. Several advantages of using binding proteins in
such uptake systems have been proposed. However, a systematic, rigorous and
quantitative analysis of the function of binding proteins is lacking. By
combining knowledge of selection pressure and physiochemical constraints, we
derive kinetic, thermodynamic, and stoichiometric properties of binding-protein
dependent transport systems that enable a maximal import activity per amount of
transporter. Under the hypothesis that this maximal specific activity of the
transport complex is the selection objective, binding protein concentrations
should exceed the concentration of both the scarce nutrient and the transporter.
This increases the encounter rate of transporter with loaded binding protein at
low substrate concentrations, thereby enhancing the affinity and specific uptake
rate. These predictions are experimentally testable, and a number of observations
confirm them.
PMID- 25846032
TI - C-reactive protein and model for end-stage liver disease score: Have we found the
fifth element?
PMID- 25846033
TI - Intrafollicular iron and ferritin in women with ovarian endometriomas.
AB - OBJECTIVE: To evaluate whether iron contained in ovarian endometriomas can
diffuse through the cyst wall and negatively affect ovarian function. DESIGN:
Prospective case series. SETTING: Infertility unit in an academic setting.
POPULATION: Thirty-nine infertile women with unilateral endometriomas who
underwent in vitro fertilization. METHODS: Iron and ferritin assessments in pools
of follicular fluids obtained from affected and contralateral intact gonads. MAIN
OUTCOME MEASURES: Iron and ferritin concentrations. RESULTS: Follicular fluid
iron content did not differ between the two gonads. The median [interquartile
range (IQR)] follicular concentrations in the affected and unaffected ovaries
were 59 (IQR 44-74) and 59 (IQR 47-73) MUg/dL, respectively (p = 0.77).
Conversely, ferritin concentration was significantly higher in affected gonads.
The median (IQR) concentrations of ferritin in the affected and unaffected
ovaries were 57 (IQR 31-146) and 33 (IQR 23-67) MUg/mL, respectively (p = 0.026).
When considering together the 78 studied ovaries, no significant correlations
emerged between follicular iron and ferritin and variables reflecting ovarian
responsiveness and oocyte developmental competence. CONCLUSIONS: Iron may diffuse
from ovarian endometriomas into the adjacent ovarian tissue. However, this
phenomenon does not appear to markedly affect ovarian function. Some effective
biological mechanisms such as ferritin storage may effectively sequester free
iron, so limiting its detrimental effects.
PMID- 25846034
TI - Introduction: free speech and the regulation of reproductive health.
PMID- 25846031
TI - Switch from oral pramipexole or ropinirole to rotigotine transdermal system in
advanced Parkinson's disease: an open-label study.
AB - OBJECTIVE: Investigate safety, feasibility and efficacy of switching therapy in
patients with advanced-stage Parkinson's disease (PD) inadequately controlled
with pramipexole (<= 3.5 mg/day) or ropinirole (<= 14 mg/day) to rotigotine
transdermal system (<= 14 mg/24 h; dose adjustments <= 16 mg/24 h permitted).
METHODS: PD0009 (ClinicalTrials.gov: NCT01711866) was an open-label study in
patients with advanced-stage PD receiving levodopa, and experiencing sleep
disturbance or early-morning motor impairment. Pramipexole/ropinirole was
switched to equivalent dose rotigotine overnight or in two stages. During the 4
week treatment period rotigotine dose adjustments were permitted (up to 16 mg/24
h). Primary variable: Clinical Global Impressions (CGI) item 4: side effects
(assessing safety) at end of treatment. RESULTS: 79/87 (91%) patients completed
the study; 2 (2%) withdrew due to adverse events (AEs). Most (84; 97%) had CGI
item 4 score < 3 indicating switch did not interfere with functioning; three
experienced drug-related AEs interfering with functioning (score = 3). 62%
patients improved on Patient Global Impression of Change, assessing
effectiveness. AEs occurring >= 5%: application site pruritus (10%), application
site erythema (7%), dizziness (7%), dyskinesia (7%), erythema (6%), pruritus
(6%). Unified Parkinson's Disease Rating Scale II and III, Parkinson's Disease
Sleep Scale-2 and Pittsburgh Sleep Quality Index were unchanged. Numerical
improvements in 'off' time, awakenings and nocturias were observed. CONCLUSIONS:
Switch from pramipexole or ropinirole to rotigotine (up to 14 mg/24 h) was
feasible and possibly associated with some benefit.
PMID- 25846035
TI - Abortion and compelled physician speech.
AB - Informed consent mandates for abortion providers may infringe the First
Amendment's freedom of speech. On the other hand, they may reinforce the
physician's duty to obtain informed consent. Courts can promote both doctrines by
ensuring that compelled physician speech pertains to medical facts about abortion
rather than abortion ideology and that compelled speech is truthful and not
misleading.
PMID- 25846036
TI - The first amendment and physician speech in reproductive decision making.
AB - Courts are divided as to whether abortion informed consent mandates violate the
First Amendment. This article argues that given the doctor's and patient's unique
expertise, the patient's strong interests in autonomous decision making, and the
fact that these laws regulate speech, rather than conduct, heighted or strict
scrutiny should apply to such mandates.
PMID- 25846037
TI - A matter of context: Casey and the constitutionality of compelled physician
speech.
AB - Under the Supreme Court's compelled speech cases, the context of government
mandated disclosures determines the standard of review. Pursuant to Casey,
Zauderer, and Whalen, compelled disclosures in the medical context, such as
speech-and-display ultrasound laws, are subject to - and survive - a form of
rational basis scrutiny.
PMID- 25846038
TI - Informed decision making and abortion: crisis pregnancy centers, informed
consent, and the first amendment.
AB - Shifting laws and regulations increasingly displace the centrality of women's
health concerns in the provision of abortion services. This is exemplified by the
growing presence of deceptive Crisis Pregnancy Centers alongside new informed
consent laws designed to dissuade women from seeking abortions. Litigation on
informed consent is further complicated in the clinical context due to the
increased mobilization of facts - such as the gestational age or sonogram of the
fetus - delivered with the intent to dissuade women from accessing abortion. In
other words, factual information utilized for ideological purpose. To preserve a
woman's autonomy and decision-making capacity, there must be a concerted effort
on the part of legislators and courts to place a woman's health at the center of
abortion law and policy.
PMID- 25846039
TI - Casey meets the crisis pregnancy centers.
AB - Recent cases have found factual disclosure requirements to be constitutional when
imposed on abortion providers but unconstitutional when imposed on crisis
pregnancy centers. This paper argues that the outcomes in both kinds of cases can
be explained by courts' perception of abortion as an ideological, political, or
moral act rather than as health care.
PMID- 25846040
TI - When states regulate emergency contraceptives like abortion, what should guide
disclosure?
AB - State laws dictating "informed consent" about surgical and chemical abortions
sometimes ensnare emergency contraceptives (EC), as the science surrounding EC
shows. Courts evaluating mandated disclosures gravitate to professional norms
rather than the information most women would value: basic factual information
about EC so that they can decide for themselves whether to use these drugs.
PMID- 25846041
TI - Are all abortions equal? Should there be exceptions to the criminalization of
abortion for rape and incest?
AB - Politics, public discourse, and legislation restricting abortion has settled on a
moderate orthodoxy: restrict abortion, but leave exceptions for pregnancies that
result from rape and incest. I challenge that consensus and suggest it may be
much harder to defend than those who support the compromise think. From both Pro
Life and Pro-Choice perspectives, there are good reasons to treat all abortions
as equal.
PMID- 25846042
TI - Acoustic separation and biomedical research: lessons from Indian regulation of
compensation for research injury.
AB - In early 2013, the Indian government introduced new rules governing the conduct
of clinical trials involving human participants. Among other provisions, the law
requires that sponsors of research compensate participants who are injured during
the course of their research participation. This article examines the effects of
India's compensation law and the efforts that policymakers in India have made to
tailor the law since its passage. I use the legal concept of acoustic separation
as a framework to explain and justify the approach that India has taken in
refining its regulation of research related injuries. I conclude that India's
example may provide useful lessons for research sponsors and lawmakers in other
regulatory states seeking to promote a well-regulated biomedical research
industry.
PMID- 25846043
TI - Detecting, preventing, and responding to "fraudsters" in internet research:
ethics and tradeoffs.
AB - Internet-based health research is increasing, and often offers financial
incentives but fraudulent behavior by participants can result. Specifically,
eligible or ineligible individuals may enter the study multiple times and receive
undeserved financial compensation. We review past experiences and approaches to
this problem and propose several new strategies. Researchers can detect and
prevent Internet research fraud in four broad ways: (1) through the
questionnaire/instrument (e.g., including certain questions in survey; and
software for administering survey); (2) through participants' non-questionnaire
data and seeking external validation (e.g., checking data for same email
addresses, usernames, passwords, and/or fake addresses or phone numbers; (3)
through computer information, (e.g., IP addresses and cookies), and 4) through
study design (e.g., avoid lump sum compensation and interviewing participants).
These approaches each have pros and cons, and raise ethical, legal, and
logistical questions, given that ethical tensions can emerge between preserving
the integrity of research vs. protecting the privacy and confidentiality of study
respondents. While past discussions concerning the ethics of online research have
tended to focus on the participants' ability to trust the researchers, needs now
arise to examine researchers' abilities to trust the participants. This analysis
has several critical implications for future practice, policy, and research.
PMID- 25846044
TI - On the justifiability of ACMG recommendations for reporting of incidental
findings in clinical exome and genome sequencing.
AB - This paper examines three possible justifications for original ACMG
recommendations to return incidental findings from whole exome or genome
sequencing independent of patient preferences. The first two potential
justifications, based on a patient's authentic values, then on harms to others,
are founding lacking as a basis of justification for these recommendations. The
third, grounded in analogous professional practices, might serve as a potential
justification if several controversies can be avoided. However, given the nature
of these controversies and the need to instill public trust in this newly
emerging science, the paper finds that updated ACMG recommendations that
recognize opt-out rights on behalf of patients is the most prudent, and
justifiable, approach.
PMID- 25846045
TI - Global justice and health systems research in low- and middle-income countries.
AB - Scholarship focusing on how international research can contribute to justice in
global health has primarily explored requirements for the conduct of clinical
trials. Yet health systems research in low- and middle-income countries (LMICs)
has increasingly been identified as vital to the reduction of health disparities
between and within countries. This paper expands an existing ethical framework
based on the health capability paradigm - research for health justice - to
externally-funded health systems research in LMICs. It argues that a specific
form of health systems research in LMICs is required if the enterprise is to
advance global health equity. "Research for health justice" requirements for
priority setting, research capacity strengthening, and post-study benefits in
health systems research are derived in light of the field's distinctive
characteristics. Specific obligations are established for external research
actors, including governments, funders, sponsors, and investigators. How these
framework requirements differ from those for international clinical research is
discussed.
PMID- 25846046
TI - The patient as consumer: empowerment or commodification? Currents in contemporary
bioethics.
AB - Discussions surrounding patient engagement and empowerment often use the terms
"patient" and "consumer" interchangeably. But do the two terms hold the same
meaning, or is a "patient" a passive actor in the health care arena and a
"consumer" an informed, rational decision-maker? Has there been a shift in our
usage of the two terms that aligns with the increasing commercialization of
health care in the U.S. or has the patient/consumer dynamic always been a part of
the buying and selling of health care in the American system? Recent discussions
of the issue exist in the popular press and in social media forums such as
TEDMED, but few direct analyses of the ethical, legal, and policy ramifications
of this possible shift in terminology are available in the academic literature.
This paper analyzes our usage of the terms and any recent changes in the dynamic
and discusses the ethical, legal, and policy implications of this simple
terminology for the physicianpatient relationship.
PMID- 25846049
TI - The Hippo pathway transcriptional co-activator, YAP, confers resistance to
cisplatin in human oral squamous cell carcinoma.
AB - Cisplatin (CDDP) is widely used to treat oral squamous cell carcinoma (OSCC),
however, many patients exhibit acquired drug resistance. Yes-associated protein
(YAP) is a transcriptional co-activator of the Hippo pathway that regulates organ
size and promotes cell proliferation. YAP overexpression correlates with
epithelial-mesenchymal transition and nodal metastasis, resulting in anti-tubulin
drug resistance. Whether YAP overexpression is the cause of CDDP resistance in
cancer cells is unclear, therefore, we investigated the correlation between YAP
expression and CDDP sensitivity. We established three CDDP-resistant cell lines
(OSC-19-R, SCCKN-R and HSC-3-R) from the OSCC parental cell lines. We also
examined the expression levels of ATP7B, GST-pi and ERCC1, which are strongly
associated with CDDP resistance, and Hippo pathway-related proteins by western
blotting. Using immunocytochemistry, we examined the cellular localization of
YAP. Additionally, following knockdown of YAP using short interfering RNAs
(siRNAs), we analyzed changes in sensitivity to CDDP. Compared with parental OSC
19 cells, OSC-19-R cells were obviously larger. Expression levels of YAP were not
significantly different between OSC-19 and OSC-19-R. However, expression levels
of phosphorylated YAP in OSC-19-R were decreased. We observed translocation of
YAP from the cytoplasm to the nucleus in OSC-19-R cells. Knockdown of YAP using
siRNAs revealed that sensitivity to CDDP was significantly increased.
Translocation of YAP correlated with the acquisition of CDDP resistance. YAP
could be a new therapeutic target for the treatment of patients with cancer that
are resistant to CDDP.
PMID- 25846048
TI - Lanthionine ketimine ester provides benefit in a mouse model of multiple
sclerosis.
AB - Lanthionine ketimine (LK) is a natural sulfur amino acid metabolite which binds
to collapsin response mediator protein-2 (CRMP2), an abundant brain protein that
interacts with multiple partners to regulate microtubule dynamics, neurite growth
and retraction, axonal transport, and neurotransmitter release. LK ethyl-ester
(LKE) is a cell-permeable synthetic derivative that promotes neurogenesis,
suppresses nitric oxide production from microglia, and reduces neurotoxicity of
microglia-conditioned medium. These properties led us to test the effects of LKE
in experimental autoimmune encephalomyelitis (EAE), a commonly used mouse model
of multiple sclerosis. Female C57Bl/6 mice were immunized with myelin
oligodendrocyte glycoprotein peptide 35-55 to develop a chronic disease. LKE was
provided in the chow at 100 ppm, ad libitum beginning when the mice reached
moderate clinical signs. Over the following 4 weeks the LKE-treated mice showed a
significant reduction in clinical signs compared to vehicle-treated mice. LKE
dose dependently reduced IFNgamma production from splenic T cells, but had no
effect on IL-17 production suggesting protective effects were mediated within the
CNS. Electron microscopy revealed that, compared to sham mice, EAE mice had
significant neurodegeneration in both the optic nerve and spinal cord, which was
reduced in the LKE-treated mice. In contrast only minimal disruption of myelin
was observed at this time point. In the optic nerve, measurements of axon caliber
and myelin thickness showed little changes between sham and EAE mice, however,
treatment with LKE increased the percentage of axons with thicker myelin and with
larger axon calibers. In the spinal cord, only smaller effects of LKE on myelin
thickness were observed. The effects of LKE were associated with a reduced
relative level of phosphorylated CRMP2 to CRMP2. Together, these results
demonstrate that LKE reduces neurodegeneration in a chronic EAE model of MS,
which could have translation potential for treatment of progressive forms of MS.
PMID- 25846050
TI - Palmitic acid, verified by lipid profiling using secondary ion mass spectrometry,
demonstrates anti-multiple myeloma activity.
AB - Recent studies indicate that lipid metabolic changes affect the survival of
multiple myeloma (MM) cells. Time-of-flight secondary ion mass spectrometry (TOF
SIMS), an imaging mass spectrometry technique, is used to visualize the
subcellular distribution of biomolecules including lipids. We therefore applied
this method to human clinical specimens to analyze the membrane fatty acid
composition and determine candidate molecules for MM therapies. We isolated MM
cells and normal plasma cells (PCs) from bone marrow aspirates of MM patients and
healthy volunteers, respectively, and these separated cells were analyzed by TOF
SIMS. Multiple ions including fatty acids were detected and their ion counts were
estimated. In MM cells, the mean intensity of palmitic acid was significantly
lower than the mean intensity in PCs. In a cell death assay, palmitic acid
reduced U266 cell viability dose-dependently at doses between 50 and 1000 MUM.
The percentage of apoptotic cells increased from 24h after palmitic acid
administration. In contrast, palmitic acid had no effect on the viability of
normal peripheral blood mononuclear cells (PBMCs). The results of this study
indicated that palmitic acid is a potential candidate for novel therapeutic
agents that specifically attack MM cells.
PMID- 25846051
TI - Can Nonurgent Emergency Department Care Costs be Reduced? Empirical Evidence from
a U.S. Nationally Representative Sample.
AB - BACKGROUND: A well-functioning primary care system has the capacity to provide
effective care for patients to avoid nonurgent emergency department (ED) use and
related costs. OBJECTIVE: This study examined how patients' perceived deficiency
in ambulatory care is associated with nonurgent ED care costs nationwide.
METHODS: This retrospective cohort study used data from the 2010-2011 Medical
Expenditure Panel Survey. This study chose usual source of care, convenience of
needed medical care, and patient evaluation of care quality as the main
independent variables. The marginal effect following a multivariate logit model
was employed to analyze the urgent vs. nonurgent ED care costs in 2011, after
controlling for covariates in 2010. The endogeneity was accounted for by the time
lag effect and controlling for education levels. Sample weights and variance were
adjusted with the survey procedures to make results nationally representative.
RESULTS: Patient-perceived poor and intermediate levels of primary care quality
had higher odds of nonurgent ED care costs (odds ratio [OR] = 2.22, p = 0.035,
and OR = 2.05, p = 0.011, respectively) compared to high-quality care, with a
marginal effect (at means) of 13.0% and 11.5% higher predicted probability of
nonurgent ED care costs. Costs related to these ambulatory care quality
deficiencies amounted to $229 million for private plans (95% confidence interval
[CI] $100 million-$358 million), $58.5 million for public plans (95% CI $33.9
million-$83.1 million), and an overall of $379 million (95% CI $229 million-$529
million) nationally. CONCLUSIONS: These findings highlight the improvement in
ambulatory care quality as the potential target area to effectively reduce
nonurgent ED care costs.
PMID- 25846052
TI - Neuronal Organization of the Brain in the Adult Amphioxus (Branchiostoma
lanceolatum): A Study With Acetylated Tubulin Immunohistochemistry.
AB - Amphioxus (Cephalochordata) belongs to the most basal extant chordates, and
knowledge of their brain organization appears to be key to deciphering the early
stages of evolution of vertebrate brains. Most comprehensive studies of the
organization of the central nervous system of adult amphioxus have investigated
the spinal cord. Some brain populations have been characterized via
neurochemistry and electron microscopy, and the overall cytoarchitecture of the
brain was studied by Ekhart et al. (2003; J. Comp. Neurol. 466:319-330) with
general staining methods and retrograde transport from the spinal cord. Here, the
cytoarchitecture of the brain of adult amphioxus Branchiostoma lanceolatum was
reinvestigated by using acetylated tubulin immunohistochemistry, which
specifically stains neurons and fibers, in combination with some ancillary
methods. This method allowed reproducible staining and mapping of types of
neuron, mostly in brain regions caudal to the entrance level of nerve 2, and its
comparison with spinal cord populations. The brain populations studied and
discussed in detail were the Retzius bipolar cells, lamellate cells, Joseph
cells, various types of translumenal cells, somatic motoneurons, Rohde nucleus
cells, small ventral multipolar neurons, and Edinger cells. These observations
expand our knowledge of the distribution of cell types and provide additional
data on the number of cells and the axonal tracts and commissural regions of the
adult amphioxus brain. The results of this comprehensive study provide a
framework for comparison of complex adult populations with the early brain
neuronal populations revealed in developmental studies of the amphioxus.
PMID- 25846053
TI - Effectiveness of a balance-training program provided by qualified care workers
for community-based older adults: A preliminary study.
AB - The purpose of this study was to determine the effectiveness of a balance
training program provided by qualified care workers (QCWs) to community-based
older adults attending day centers. Weekly balance training was conducted by QCWs
working at day centers over a 6-month period. Fall risk factors, fear of falling,
and physical function were compared between balance-training (n = 22) and control
(n = 23) groups at baseline and after 6 months of intervention. Physical function
assessments included the following: one-leg standing test, chair-standing test
(CST), timed up-and-go test (TUGT), and a lower-extremity muscle strength test
(LEST). Participants who underwent balance training significantly improved in the
CST and LEST, and had reduced fear and risk of falling compared with the control
group (p < 0.05). In the balance-training group, the TUGT was significantly
better at 6 months than at baseline (p < 0.05). A balance-training program for
community-dwelling older adults can be effectively implemented by QCWs.
PMID- 25846054
TI - Effects of garlic oil, nitrate, saponin and their combinations supplemented to
different substrates on in vitro fermentation, ruminal methanogenesis, and
abundance and diversity of microbial populations.
AB - AIMS: To investigate the effect of garlic oil (G), nitrate (N), saponin (S) and
their combinations supplemented to different forage to concentrate substrates on
methanogenesis, fermentation, diversity and abundances of bacteria and Archaea in
vitro. METHODS AND RESULTS: The study was conducted in an 8 * 2 factorial design
with eight treatments and two substrates using mixed ruminal batch cultures
obtained. Quillaja S (0.6 g l(-1) ), N (5 mmol l(-1) ) and G (0.27 g l(-1) ) were
used separately or in binary and tertiary combinations. The two substrates
contained grass hay and a dairy concentrate mixture at a 70 : 30 (high-forage
substrate) ratio or a 30 : 70 (high-concentrate substrate) ratio. Ruminal
fermentation and cellulolytic bacterial populations were affected by interaction
between substrate and anti-methanogenic compounds. The inhibitor combinations
decreased the methane production additively regardless of substrate. For the high
concentrate substrate, S decreased methane production to a greater extent, so did
G and N individually for the high-forage substrate. Feed degradability and total
volatile fatty acid (VFA) concentrations were not decreased by any of the
treatments. Fibre degradability was actually improved by N+S for the high-forage
substrate. VFA concentrations and profiles were affected differently by different
anti-methanogenic inhibitors and their combinations. All treatments inhibited the
growth of Archaea, but the effect on Fibrobacter succinogenes, Ruminococcus albus
and Ruminococcus flavefaciens varied. CONCLUSIONS: The results suggest that
substrate influences the efficacy of these inhibitors when they are used
separately, but in combinations, they can lower methanogenesis additively without
much influence from the substrate. SIGNIFICANCE AND IMPACT OF THE STUDY: The
presented research provided evidence that binary and tertiary combination of
garlic oil, nitrate and saponin can lower the methane production additively
without adversely impacting rumen fermentation and degradability, and forage to
concentrate ratio does not change the above effects. These anti-methanogenic
inhibitors in combination may have practical application to mitigate methane
emission from ruminants.
PMID- 25846056
TI - Haploinsufficiency of ANO6, NELL2 and DBX2 in a boy with intellectual disability
and growth delay.
AB - We report on a 10-year-old-boy presenting with moderate intellectual disability
(ID), impaired motor skills, hypotonia, growth delay, minor anomalies, misaligned
teeth, pectus excavatum, small hands and feet, widely spaced nipples, and a 1.13
Mb de novo deletion on HSA12q12 (chr12:44,830,147-45,964,945 bp, hg19), deleting
ANO6, NELL2, and DBX2 and the pseudogenes PLEKHA8P1 and RACGAP1P. We suggest DBX2
and NELL2 as disease-causing genes and their haploinsufficiency to be involved in
the psychomotor delay in the patient. DBX2 encodes a homeobox protein, highly
expressed during neuronal development and regulating differentiation of
interneurons in brain and spinal cord. NELL2 is expressed in most of the central
and peripheral nervous system, with highest expression in hippocampus and
cerebellum, maximizing during neuronal differentiation. The deletion in our
patient is the smallest in HSA12q12 reported to date, and it is included in the
deletion carried by four previously reported patients. The clinical presentation
of these patients points to the recurrence of the following manifestation,
possibly delineating a 12q12 deletion syndrome phenotype: moderate to severe
developmental/intellectual delay, hypotonia, postnatal growth retardation,
skeletal and dental anomalies, minor facial anomalies including strabismus, down
slanting palpebral fissures, and large/low-set ears.
PMID- 25846055
TI - Oral administration of non-absorbable delayed release 6-mercaptopurine is locally
active in the gut, exerts a systemic immune effect and alleviates Crohn's disease
with low rate of side effects: results of double blind Phase II clinical trial.
AB - Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side
effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR
6MP) was developed, with local effect on the gut immune system and minimal
absorption. The aim of this study was to evaluate the safety and efficacy of DR
6MP in patients with moderately severe CD compared to systemically delivered 6
mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week,
double-blind controlled trial. The primary end-point was the percentage of
subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or
clinical response (100-point CDAI reduction). Twenty-six (56.5%) and 13 (54.2%)
subjects from the DR-6MP and Purinethol cohorts, respectively, completed the
study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment.
However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12
weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical
remission at week 8. A greater improvement in Inflammatory Bowel Disease
Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a
decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte
adhesion to site of inflammation. DR-6MP was safer than Purinethol, with
significantly fewer adverse events (AEs). There was no evidence of drug-induced
leucopenia in the DR-6MP group; the proportion of subjects who developed
hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and
biologically active in the gut. It is clinically effective, exerting a systemic
immune response with low systemic bioavailability and a low incidence of side
effects.
PMID- 25846057
TI - Effective climate change refugia for coral reefs.
PMID- 25846058
TI - Ratiometric fluorescence detection of tyrosinase activity and dopamine using
thiolate-protected gold nanoclusters.
AB - In this work, a sensitive and selective ratiometric fluorescence sensing platform
was built for the detection of tyrosinase (TYR) activity and dopamine (DA) using
glutathione (GSH) protected gold nanoclusters (Au NCs) as probes. Upon excitation
at 350 nm, Au NCs displayed an intense red emission, which could be effectively
quenched by quinones. TYR, a typical polyphenol oxidase, can catalyze the
oxidization of DA to o-quinone and therefore quenched the fluorescence of Au NCs.
Moreover, the reaction of TYR and DA gave rise to an emission band at 400 nm,
which increased in a TYR/DA-concentration-dependent manner. The ratiometric
signal variations were utilized for facile, sensitive, and selective detection of
TYR activity and DA. A linear range was obtained from 0.006-3.6 unit mL(-1) of
TYR activity, while the linear range for detection of DA was 1.0 nM to 1.0 mM.
Additionally, it constructed a useful platform for TYR inhibitor screening in
biomedical research.
PMID- 25846059
TI - Carotenoid-enriched transgenic corn delivers bioavailable carotenoids to poultry
and protects them against coccidiosis.
AB - Carotenoids are health-promoting organic molecules that act as antioxidants and
essential nutrients. We show that chickens raised on a diet enriched with an
engineered corn variety containing very high levels of four key carotenoids (beta
carotene, lycopene, zeaxanthin and lutein) are healthy and accumulate more
bioavailable carotenoids in peripheral tissues, muscle, skin and fat, and more
retinol in the liver, than birds fed on standard corn diets (including commercial
corn supplemented with colour additives). Birds were challenged with the
protozoan parasite Eimeria tenella and those on the high-carotenoid diet grew
normally, suffered only mild disease symptoms (diarrhoea, footpad dermatitis and
digital ulcers) and had lower faecal oocyst counts than birds on the control
diet. Our results demonstrate that carotenoid-rich corn maintains poultry health
and increases the nutritional value of poultry products without the use of feed
additives.
PMID- 25846060
TI - Sulfakinin is an important regulator of digestive processes in the migratory
locust, Locusta migratoria.
AB - Sulfakinin (SK) is a sulfated insect neuropeptide that is best known for its
function as a satiety factor. It displays structural and functional similarities
with the vertebrate peptides gastrin and cholecystokinin. Peptidomic studies in
multiple insects, crustaceans and arachnids have revealed the widespread
occurrence of SK in the arthropod phylum. Multiple studies in hemi- and
holometabolous insects revealed the pleiotropic nature of this neuropeptide: in
addition to its activity as a satiety factor, SK was also reported to affect
muscle contraction, digestive enzyme release, odor preference, aggression and
metabolism. However, the main site of action seems to be the digestive system of
insects. In this study, we have investigated whether SK can intervene in the
control of nutrient uptake and digestion in the migratory locust (Locusta
migratoria). We provide evidence that sulfakinin reduces food uptake in this
species. Furthermore, we discovered that SK has very pronounced effects on the
main digestive enzyme secreting parts of the locust gut. It effectively reduced
digestive enzyme secretion from both the midgut and gastric caeca. SK injection
also elicited a reduction in absorbance and proteolytic activity of the gastric
caeca contents. The characteristic sulfation of the tyrosine residue is crucial
for the observed effects on digestive enzyme secretion. In an attempt to provide
potential leads for the development of peptidomimetic compounds based on SK, we
also tested two mimetic analogs of the natural peptide ligand in the digestive
enzyme secretion assay. These analogs were able to mimic the effect of the
natural SK, but their effects were milder. The results of this study provide new
insights into the action of SK on the digestive system in (hemimetabolous)
insects.
PMID- 25846061
TI - Chemical exposures in the workplace and breast cancer risk: A prospective cohort
study.
AB - We investigated the relationship between workplace chemical exposures and breast
cancer risk among women enrolled in the Sister Study, a prospective cohort study
of US and Puerto Rican women. A total of 47,640 participants reported work
outside of the home. Workplace exposure to eleven agents (acids, dyes or inks,
gasoline or other petroleum products, glues or adhesives, lubricating oils,
metals, paints, pesticides, soldering materials, solvents and stains or
varnishes) was characterized based on self-reports of frequency and duration of
use. Approximately 14% of the study population reported exposure to only one
agent and 11% reported working with two or more of the 11 agents in their
lifetime. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated
for each agent, adjusting for established breast cancer risk factors. During
follow-up, 1,966 cases of breast cancer were reported. Although there were no
significant associations between ever use of the eleven agents evaluated and
breast cancer risk, women with cumulative exposure to gasoline or petroleum
products at or above the highest quartile cutoff had an elevated risk of total
(HR: 2.3, 95%CI: 1.1-4.9) and invasive (HR: 2.5, 95%CI: 1.1-5.9) breast cancer
compared with women in the lowest quartile group (ptrend = 0.03). Workplace
exposure to soldering materials was associated with an increased risk of
premenopausal breast cancer (HR = 1.8, 95% CI = 1.1-3.0). Findings support the
need for further studies to elucidate the role of occupational chemicals in
breast cancer etiology.
PMID- 25846062
TI - Effectiveness of motor practice in lucid dreams: a comparison with physical and
mental practice.
AB - Motor practice in lucid dreams is a form of mental rehearsal where the dreamer
can consciously rehearse motor skills in the dream state while being physically
asleep. A previous pilot study showed that practice in lucid dreams can improve
subsequent performance. This study aimed to replicate those findings with a
different task (finger-tapping) and compare the effectiveness of lucid dream
practice (LDP) not only to physical but also to mental practice (MP) in
wakefulness. An online experiment was completed by 68 participants within four
groups: LDP group, MP group, physical practice (PP) group and control (no
practice) group. Pre-test was accomplished in the evening, post-test in the next
morning, while the practice was done during the night. All three practice groups
significantly improved their performance from pre-test to post-test, but no
significant improvements were observed for the control group. Subjective sleep
quality was not affected by night practice. This study thus corroborates the
previous findings that practice in lucid dreams is effective in improving
performance. Its effects seem to be similar to actual PP and MP in wakefulness.
Future studies should establish reliable techniques for lucid dream induction and
verify the effects of LDP in sleep laboratory conditions.
PMID- 25846063
TI - The shape of middle cerebral artery and plaque location: high-resolution MRI
finding.
AB - BACKGROUND: The location of plaque may be associated with the vascular geometry.
AIM: We aimed to examine the relationship between the geometry of middle cerebral
artery and the plaque location detected by high-resolution magnetic resonance
imaging. METHODS: Among patients with a single subcortical infarction without a
significant middle cerebral artery stenosis on magnetic resonance angiography,
those with a plaque detected from high-resolution magnetic resonance imaging were
prospectively enrolled. The shape of middle cerebral artery was measured from the
coronal view, and was classified as straight, U-shaped, inverted U-shaped, and S
shaped. The location of the plaque was divided into superior and inferior, and
analyzed according to the shape of middle cerebral artery. RESULTS: Among the 40
patients, the shape of middle cerebral artery was straight in 7 (17.5%), U-shaped
in 10 (15.0%), inverted U-shaped in 11 (27.5%), and S-shaped in 12 patients
(30.0%). The superior plaque was more closely associated with straight (85.7%) or
U-shaped middle cerebral arteries (90.0%), whereas inverted U-shaped (81.8%) and
S-shaped middle cerebral arteries (75.0%) were more often associated with
inferior plaque. The prevalence of symptomatic plaque was higher in superior than
inferior plaques (70.0% vs. 25.0%, P = 0.004). Multivariate analysis showed that
straight and U-shaped middle cerebral artery was the only significant factor
associated with the superior plaque. CONCLUSION: The shape of middle cerebral
artery may be a factor determining the location of early atherosclerotic plaque.
PMID- 25846064
TI - Genomic and Proteomic Analysis of Escherichia coli After Spaceflight Reveals
Changes Involving Metabolic Pathways.
AB - BACKGROUND AND AIMS: The space environment could have impacts on a variety of
characteristics of microorganism such as cell metabolism, drug resistance, and
virulence. However, relevant mechanisms need to be clarified. In the present
study, the effect of a space environment on Escherichia coli was investigated.
METHODS: E. coli strains were sent to space for 398 h on the Shenzhou VIII and
ground simulation was conducted as control. After the flight, a mutant strain LCT
EC67 was selected for further analysis. RESULTS: Although no changes in
hemolysis, morphology or antibiotic sensitivity were observed, the mutant strain
showed elevated carbon source utilization compared with the control group.
Genomic and proteomic analyses showed that 801 genes were upregulated and 825
genes were downregulated. In addition, 167 proteins were overexpressed and 92
proteins were downregulated using a cut-off fold-change value of 1.4 and a p <
0.05. The changed proteins were associated with metabolic functions such as
alanine and glutamate metabolism, arginine and proline metabolism, and fatty acid
and propanoate metabolism. CONCLUSIONS: E. coli showed alterations at gene and
protein levels mainly regarding biochemical metabolism after spaceflight.
PMID- 25846065
TI - Antileishmanial pharmacomodulation in 8-nitroquinolin-2(1H)-one series.
AB - An antileishmanial pharmacomodulation at position 4 of 8-nitroquinolin-2(1H)-one
was conducted by using the Sonogashira and Suzuki-Miyaura coupling reactions. A
series of 25 derivatives was tested in vitro on the promastigote stage of
Leishmania donovani along with an in vitro cytotoxicity evaluation on the human
HepG2 cell line. Only the derivatives bearing a phenyl moiety at position 4 of
the quinoline ring displayed interesting biologic profile, when the phenyl moiety
was substituted at the para position by a Br or Cl atom, or by a CF3 group. Among
them, molecules 17 and 19 were the most selective and were then tested in vitro
on the intracellular amastigote stage of both L. donovani and Leishmania
infantum, in parallel with complementary in vitro cytotoxicity assays on the
macrophage cell lines THP-1 and J774A.1. Molecule 19 showed no activity on the
amastigote stages of the parasites and some cytotoxicity on the J774A.1 cell line
while molecule 17, less cytotoxic than 19, showed anti-amastigote activity in L.
infantum, being 3 times less active than miltefosine but more active and
selective than pentamidine. Nevertheless, hit-molecule 17 did not appear as
selective as the parent compound.
PMID- 25846066
TI - Synthesis of a new series of dithiocarbamates with effective human carbonic
anhydrase inhibitory activity and antiglaucoma action.
AB - A new series of dithiocarbamates (DTCs) was prepared from primary/secondary
amines incorporating amino/hydroxyl-alkyl, mono- and bicyclic aliphatic ring
systems based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino
substituted piperidine, morpholine and piperazine scaffolds, and carbon
disulfide. The compounds were investigated for the inhibition of four mammalian
alpha-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, that is,
the human (h) hCA I, II, IX and XII, drug targets for antiglaucoma (hCA II and
XII) or antitumor (hCA IX/XII) agents. The compounds were moderate or inefficient
hCA I inhibitors (off-target isoform for both applications), efficiently
inhibited hCA II, whereas some of them were low nanomolar/subnanomolar hCA IX/XII
inhibitors. One DTC showed excellent intraocular pressure (IOP) lowering
properties in an animal model of glaucoma, with a two times better efficiency
compared to the clinically used sulfonamide dorzolamide.
PMID- 25846067
TI - Effect of long-term Helicobacter pylori infection on growth of children: a cohort
study.
AB - BACKGROUND: The effects of Helicobacter pylori (H. pylori) infection on growth
are a controversial issue. We investigated the effects of long-term H. pylori
infection on height and weight in children. METHODS: A total of 200 children of 7
18 years old suffering from dyspeptic complaints were classified into two groups:
H. pylori positive and negative groups, respectively. Whether the infection was
impoved was followed up while performing urea breath test, and according to
exposure time to the infection, the children were further divided into group 1
(<=1.5 months), group 2 (>1.5-<=6 months) and group 3 (>6 months). Antropometric
measurements were obtained and repeated every six months. RESULTS: Mean growth
velocity scores in the H. pylori positive and negative groups were 0.49+/-3.85
[95% confidence interval (CI): -0.21-1.18] and 1.98+/-4.42 (95% CI: 1-2.96),
respectively. The difference between both groups was statistically significant
(P=0.012). Mean growth velocity scores in groups 1, 2 and 3 were 0.96+/-3.84,
0.16+/-4.51 and -0.85+/-3.09, respectively. Mean growth velocity scores of group
3 were significantly lower than those of groups 0 and 1 (P=0.005 and P=0.041).
The mean weight scores in group 3 were similar to those in group 2, but the
scores in group 3 were significantly lower than those in group 1 (-1.75+/-1.05,
1.21+/-1.37 and -0.88+/-1.49, respectively). CONCLUSION: As the duration of
exposure is prolonged in children with H. pylori infection, the negative effect
of the infection on both height and weight is evident.
PMID- 25846068
TI - Weaning preterm infants from continuous positive airway pressure: evidence for
best practice.
AB - BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is frequently used
in preterm infants. However, there is no consensus on when and how to wean them
from NCPAP. DATA SOURCES: Based on recent publications, we have reviewed the
criteria of readiness-to-wean and factors affecting weaning success. A special
focus is placed on the methods of weaning from NCPAP in preterm infants. RESULTS:
Practical points of when and how to wean from NCPAP in preterm infants are
explained. Preterm infants are ready to be weaned from NCPAP when they are stable
on a low NCPAP pressure with no (or minimal) oxygen requirement. Methods used to
wean from NCPAP include: sudden weaning of NCPAP, gradual decrease of NCPAP
pressure, graded-timeoff NCPAP (cycling), weaning to high or low flow nasal
cannula, and a combination of these methods. The best strategy for weaning is yet
to be determined. Cyclingoff NCPAP increases the duration of NCPAP and length of
hospital stay without beneficial effect on success of weaning. Gradual decrease
of NCPAP pressure is more physiological and better tolerated than cycling-off
NCPAP. CONCLUSION: Further studies are needed to reach a consensus regarding the
optimal timing and the best method for weaning from NCPAP in preterm infants.
PMID- 25846069
TI - The correlation between plasma cytokine levels in jaundice-free children with
biliary atresia.
AB - BACKGROUND: T helper (Th) cell cytokines modulate inflammation and play a role in
biliary atresia (BA). The aim of the study is a cross-sectional assessment of the
levels of Th cytokines in the jaundice-free post Kasai procedure patients.
METHODS: There were 40 jaundice-free patients with BA and 28 normal controls
enrolled. Patients were divided into 3 groups, including normal liver function,
impaired liver function, and portal hypertension. Plasma concentration of Th1
[interferon-gamma (INF-gamma), interleukin (IL)-2], Th2 (IL-4, IL-10), Th3
[transforming growth factor-beta1 (TGF-beta1)], Th17 (IL-17) cytokines, and
stromal cell-derived factor-1alpha (SDF-1alpha) were investigated. RESULTS: The
IFN-gamma level was significantly higher in the BA patients with impaired liver
function and portal hypertension than controls (P<0.0001 and P<0.0001,
respectively). There was a significantly increase of TGF-beta1 in all BA groups
compared with controls (P=0.003). The reduction of SDF-1alpha expression was
found in BA groups (P<0.0001). IL-10 levels significantly correlated with
aspartate aminotransferase to platelet ratio index (r=0.496, P=0.001). For the
cytokine correlations, there were no correlations of Th1, Th2 and Th17 cytokine
with the other measured cytokines, but TGF-beta1 was negatively correlated with
SDF-1alpha levels (r=-0.327, P=0.039). CONCLUSIONS: IFN-gamma and IL-10 are
likely to be involved in the disease progression in BA. Besides, TGF-beta1 is
found to be a suppression marker associated with SDF-1alpha levels and reduced
production of TGF-beta1 may be associated with the disease progression.
PMID- 25846070
TI - Characteristics of respiratory syncytial virus-induced bronchiolitis co-infection
with Mycoplasma pneumoniae and add-on therapy with montelukast.
AB - BACKGROUND: The influence of Mycoplasma pneumoniae (MP) infection on
bronchiolitis remains unclear. Additionally, reports on the efficacies of
leukotriene receptor antagonists in the treatment of bronchiolitis have been
inconclusive. METHODS: Children with respiratory syncytial virus (RSV)-induced
bronchiolitis were divided into two groups: RSV+MP group and RSV group. Each
group was randomly divided into two subgroups: one received routine and placebo
treatment, while the other received routine and montelukast treatment for 9
months. The cumulative numbers of wheezing episodes and recurrent respiratory
tract infections were recorded. Blood parameters were determined. RESULTS:
Patients in the RSV+MP group exhibited an older average age, fever, more frequent
flaky and patchy shadows in chest X-rays, more frequent extrapulmonary
manifestations, and longer hospital stays compared with patients in the RSV
group. Additionally, higher baseline blood eosinophil counts, eosinophil cationic
protein (ECP), total immunoglobulin E (IgE), interleukin (IL)-4, IL-5, IL
4/interferon-gamma ratios, leukotriene (LT) B4, and LTC4, and lower baseline
lipoxin A4 (LXA4)/LTB4 ratios were observed in the RSV+MP group compared with the
RSV group. Montelukast treatment decreased the cumulative numbers of recurrent
wheezing episodes and recurrent respiratory tract infections at 9 and 12 months.
This efficacy may be related to the montelukast-induced reductions in peripheral
eosinophil counts, ECP and total IgE, as well as the montelukast-dependent
recovery in T helper (Th) 1/Th2 balance and LXA4/LTB4 ratios in children with
bronchiolitis. CONCLUSIONS: RSV bronchiolitis with MP infection was associated
with clinical and laboratory features that differed from those of RSV
bronchiolitis without MP infection. Add-on therapy with montelukast for 9 months
was beneficial for children with bronchiolitis at 9 and 12 months after the
initiation of treatment.
PMID- 25846071
TI - Effects of Bifidobacterium supplementation on intestinal microbiota composition
and the immune response in healthy infants.
AB - BACKGROUND: Intestinal microbiotas are thought to be the most important source of
maturational stimuli to the development of the immune system. However, few
studies have focused on the development of T helper (Th) 1 immune response and
antibody response to vaccinations in healthy infants, especially in a large
cohort. Through this randomized, double-blind control trial, we investigated the
effects of Bifidobacterium longum BB536 (BB536) supplementation on intestinal
microbiota composition and the immune response in term infants. METHODS: In
total, 300 healthy newborns were recruited, randomized and fed formula either
supplemented with BB536 or with no supplementation. Stool samples were analyzed
at months 2, 4 and 11. The representative cytokine for Th1 [interferon-gamma (IFN
gamma)] and Th2 [interleukin-4 (IL-4)] secretion cells were measured using enzyme
linked immunospot assay at 4 and 7 months of age. The antibody response to
vaccines was measured at months 7 and 11. RESULTS: A total of 264 infants
completed the study. The amount of bifidobacteria and the bifidobacteria/
Enterobacteriaceae ratio (B/E) were significantly higher in the BB536
supplementation group at months 2 and 4. The number of IFN-gamma secretion cells
and the ratio of IFN-gamma/IL-4 secretion cells were increased in the BB536
supplementation group at 7 months. Moreover, the higher value of B/E in the early
stages seems to be related to the increased Th1 response. No difference was
observed between groups in the antibody response after vaccination. CONCLUSION:
BB536 has positive effects on establishing a healthy intestinal microbiota early
in life, and it also plays an important role in improving the Th1 immune
response.
PMID- 25846072
TI - Mean platelet volume in patients with varicocele.
PMID- 25846073
TI - Mean platelet volume may not be related to the physiopathology of varicocele.
PMID- 25846074
TI - The Role of C5a Receptor Signaling in Endotoxin-Induced Miscarriage and Preterm
Birth.
AB - PROBLEM: Complement factor 5a (C5a), a potent pro-inflammatory mediator of the
complement system, has been implicated in fetal rejection throughout gestation,
from miscarriage to preterm birth. This study aimed to investigate the role of
the principal C5a receptor, C5aR1 (CD88), in both miscarriage and preterm birth,
in a bacterial endotoxin (lipopolysaccharide; LPS) murine model. METHOD OF STUDY:
Wild-type and C5ar1 knockout mice were administered LPS at 9.5 or 15.5 days post
conception to induce miscarriage or preterm birth, respectively. RESULTS: C5ar1
knockout mice were protected against miscarriage in response to administration of
LPS in early gestation. However, the absence of C5aR1 had no effect on the rates
of preterm birth when LPS was administered in late gestation. CONCLUSION: There
may be a gestational window in which excessive activation of C5a can exert
deleterious effects in pregnancy. Future strategies targeting the C5a-C5aR1
signaling axis should be considered to ameliorate miscarriages in patients with
recurrent pregnancy loss.
PMID- 25846075
TI - Secreted Frizzled-related protein 3 (sFRP3)-mediated suppression of interleukin-6
receptor release by A disintegrin and metalloprotease 17 (ADAM17) is abrogated in
the osteoarthritis-associated rare double variant of sFRP3.
AB - To avoid malformation and disease, tissue development and homoeostasis are co
ordinated precisely in time and space. Secreted Frizzled-related protein 3
(sFRP3), encoded by the Frizzled-related protein gene (FRZB), acts as an
antagonist of Wnt signalling in bone development by delaying the maturation of
proliferative chondrocytes into hypertrophic chondrocytes. A disintegrin and
metalloprotease 17 (ADAM17) is a transmembrane protease that is essential for
developmental processes and promotes cartilage maturation into bone. sFRP3 is
chondroprotective and is expressed in chondrocytes of healthy articular
cartilage. Upon damage to cartilage, sFRP3 is down-regulated. Rare variants of
sFRP3 are associated with osteoarthritis. The present study demonstrates a novel
function of sFRP3 in suppression of the enzymatic activity of ADAM17 which
results in the inhibition of ADAM17-meditated interleukin-6 receptor (IL-6R)
shedding. By contrast, the rare double variant of sFRP3 failed to suppress
ADAM17. The shed soluble IL-6R (sIL-6R) is linked to inflammation, cartilage
degeneration and osteolysis. Accordingly, enhanced activity of ADAM17 in
cartilage, caused by the expression of the rare double sFRP3 variant, provides an
explanation for the genetic effect of sFRP3 variants in joint disease. The
finding that sFRP3 interacts with the ADAM17 substrate IL-6R also suggests a new
regulatory mechanism by which the substrate is protected against shedding.
PMID- 25846076
TI - Multidetector computed tomography pulmonary angiography in childhood acute
pulmonary embolism.
AB - Pulmonary embolism is a life-threatening condition affecting people of all ages.
Multidetector row CT pulmonary angiography has improved the imaging of pulmonary
embolism in both adults and children and is now regarded as the routine modality
for detection of pulmonary embolism. Advanced CT pulmonary angiography techniques
developed in recent years, such as dual-energy CT, have been applied as a one
stop modality for pulmonary embolism diagnosis in children, as they can
simultaneously provide anatomical and functional information. We discuss CT
pulmonary angiography techniques, common and uncommon findings of pulmonary
embolism in both conventional and dual-energy CT pulmonary angiography, and
radiation dose considerations.
PMID- 25846077
TI - The value of repeat scintigraphy in patients with a high clinical suspicion for
Meckel diverticulum after a negative or equivocal first Meckel scan.
AB - BACKGROUND: Technetium (99m)Tc-pertechnetate is the most common and accurate
noninvasive method of preoperative investigation for Meckel diverticulum. Despite
introducing various methods to increase the sensitivity of the study, there are
many case reports of false-negative Meckel scans. A repeat scan is sometimes
requested in patients with a high suspicion for Meckel diverticulum and negative
or equivocal first Meckel scan. OBJECTIVES: The purpose of this retrospective
study is to evaluate the value of repeat scintigraphy for these patients.
MATERIALS AND METHODS: Seven hundred fifty-three Meckel scans were recorded
retrospectively. In 33 cases (22 male and 11 female; mean age: 6.8 years), the
Meckel scintigraphy was repeated either due to a high clinical suspicion of
Meckel diverticulum and a negative study (n = 21) or due to equivocal findings in
the first scan (n = 12). The study was interpreted as positive if an abnormal
focal activity was identified in the abdomen and pelvis during the procedure. The
results were correlated with pathology and clinical symptoms. RESULTS: Seven out
of 12 (58%) equivocal studies were positive on the second study. Six of them were
proven to be positive at operation (confirmed by pathology) while one of them was
negative on laparoscopy. From 21 negative first scans with a high suspicion for
Meckel diverticulum, three (14%) were positive on the second study. All three
were proven to be Meckel diverticulum on pathology. CONCLUSION: Repeat Meckel
scans in patients with equivocal findings on the first study or a negative result
with a high clinical suspicion for a Meckel diverticulum are useful especially in
cases in which the first study had been done without appropriate preparation.
PMID- 25846081
TI - Novel mutations of low-density lipoprotein receptor gene in China patients with
familial hypercholesterolemia.
AB - Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder,
associated with elevated level of serum low-density lipoprotein-cholesterol (LDL
C), which can lead to premature cardiovascular disease (CVD). Mutations in low
density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin
type 9 (PCSK9) have been identified to be the underlying cause of this disease.
Genetic research of FH has already been extensively studied all over the world.
However, reports of FH mutations in the Chinese population are still limited. In
this paper, 20 unrelated FH families were enrolled to detect the candidate gene
variants in Chinese FH population by DNA direct sequencing. We identified 12 LDLR
variants in 13 FH probands. Importantly, we first reported two unique mutations
(c.2000_2000 delG/p.C667LfsX6 and c.605T>C/p.F202S) in LDLR gene. Our discoveries
expand the spectrum of LDLR mutations and contribute to the genetic diagnosis and
counseling for FH patients.
PMID- 25846082
TI - Dangers of direct-to-consumer advertising exposed again.
PMID- 25846083
TI - Tackling the cancer epidemic.
PMID- 25846084
TI - Non-inferiority trials: why oncologists must remain wary.
PMID- 25846085
TI - Probiotics and cancer: ready for meal time?
PMID- 25846087
TI - Adjuvant chemotherapy for rectal cancer.
PMID- 25846088
TI - Adjuvant chemotherapy for rectal cancer.
PMID- 25846089
TI - Adjuvant chemotherapy for rectal cancer.
PMID- 25846090
TI - Adjuvant chemotherapy for rectal cancer.
PMID- 25846091
TI - Adjuvant chemotherapy for rectal cancer - authors' reply.
PMID- 25846092
TI - Panitumumab for locally advanced head and neck squamous-cell carcinoma.
PMID- 25846093
TI - Radiotherapy dose and fractionation for stage III NSCLC.
PMID- 25846094
TI - Correction to Lancet Oncol 2015; 16: 60, 61. Safety and activity of blinatumomab
for adult patients with relapsed or refractory B-precursor acute lymphoblastic
leukaemia: a multi-centre, single-arm, phase 2 study.
PMID- 25846095
TI - Correction to Lancet Oncol 2014; 15: 856. Olaparib maintenance therapy in
patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned
retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial.
PMID- 25846096
TI - Transformation from non-small-cell lung cancer to small-cell lung cancer:
molecular drivers and cells of origin.
AB - Lung cancer is the most common cause of cancer deaths worldwide. The two broad
histological subtypes of lung cancer are small-cell lung cancer (SCLC), which is
the cause of 15% of cases, and non-small-cell lung cancer (NSCLC), which accounts
for 85% of cases and includes adenocarcinoma, squamous-cell carcinoma, and large
cell carcinoma. Although NSCLC and SCLC are commonly thought to be different
diseases owing to their distinct biology and genomic abnormalities, the idea that
these malignant disorders might share common cells of origin has been gaining
support. This idea has been supported by the unexpected findings that a subset of
NSCLCs with mutated EGFR return as SCLC when resistance to EGFR tyrosine kinase
inhibitors develops. Additionally, other case reports have described the
coexistence of NSCLC and SCLC, further challenging the commonly accepted view of
their distinct lineages. Here, we summarise the published clinical observations
and biology underlying tumours with combined SCLC and NSCLC histology and cancers
that transform from adenocarcinoma to SCLC. We also discuss pre-clinical studies
pointing to common potential cells of origin, and speculate how the distinct
paths of differentiation are determined by the genomics of each disease.
PMID- 25846098
TI - Nail toxicities induced by systemic anticancer treatments.
AB - Patients treated with systemic anticancer drugs often show changes to their
nails, which are usually well tolerated and disappear on cessation of treatment.
However, some nail toxicities can cause pain and functional impairment and thus
substantially affect a patient's quality of life, especially if they are given
taxanes or EGFR inhibitors. These nail toxicities can affect both the nail plate
and bed, and might present as melanonychia, leukonychia, onycholysis,
onychomadesis, Beau's lines, or onychorrhexis, as frequently noted with
conventional chemotherapies. Additionally, the periungual area (perionychium) of
the nail might be affected by paronychia or pyogenic granuloma, especially in
patients treated with drugs targeting EGFR or MEK. We review the nail changes
induced by conventional chemotherapies and those associated with the use of
targeted anticancer drugs and discuss preventive or curative options.
PMID- 25846097
TI - Nomograms in oncology: more than meets the eye.
AB - Nomograms are widely used as prognostic devices in oncology and medicine. With
the ability to generate an individual probability of a clinical event by
integrating diverse prognostic and determinant variables, nomograms meet our
desire for biologically and clinically integrated models and fulfill our drive
towards personalised medicine. Rapid computation through user-friendly digital
interfaces, together with increased accuracy, and more easily understood
prognoses compared with conventional staging, allow for seamless incorporation of
nomogram-derived prognosis to aid clinical decision making. This has led to the
appearance of many nomograms on the internet and in medical journals, and an
increase in nomogram use by patients and physicians alike. However, the
statistical foundations of nomogram construction, their precise interpretation,
and evidence supporting their use are generally misunderstood. This issue is
leading to an under-appreciation of the inherent uncertainties regarding nomogram
use. We provide a systematic, practical approach to evaluating and comprehending
nomogram-derived prognoses, with particular emphasis on clarifying common
misconceptions and highlighting limitations.
PMID- 25846099
TI - Accepting risk in the acceleration of drug development for rare cancers.
AB - Rare cancers collectively contribute a disproportionate fraction of the total
burden of cancer. The oncology community is increasingly facing small numbers of
patients with each cancer subtype, requiring cooperation and collaboration to
complete multicentre trials that advance knowledge and patient care. At the same
time, new insights into the biology of rare cancers have led to an explosion in
knowledge and development of targeted agents. These insights and techniques are
set to revolutionise the care of patients with cancer. However, drug development
strategies and the availability of new agents for rare cancers are at risk of
stalling owing to the ever-increasing complexity and costs of clinical trials.
Finding solutions to these problems is imperative to the future of cancer care.
We propose that a greater degree of risk sharing is needed than is currently
accepted to enable the use of new methods with confidence, and to keep pace with
scientific advancement.
PMID- 25846100
TI - Autologous human nasal epithelial cell sheet using temperature-responsive culture
insert for transplantation after middle ear surgery.
AB - Postoperative mucosal regeneration of the middle ear cavity and the mastoid
cavity is of great importance after middle ear surgery. However, the
epithelialization of the mucosa in the middle ear is retarded because chronic
inflammation without epithelialization aggravates gas exchange and clinical
function. These environmental conditions in the middle ear lead to postoperative
retraction and adhesion of the newly-formed tympanic membrane. Therefore, if the
mucosa on the exposed middle ear bone surface can be rapidly regenerated after
surgery, the surgical treatments for cholesteatoma and adhesive middle ear
disease can potentially be improved. In this study, we successfully generated a
cell sheet designed for the postoperative treatment of cholesteatoma. We used
nasal cells to create an artificial middle ear mucosal cell sheet with a three
dimensional (3D) configuration similar to that of the middle ear mucosa. The
sheets consisted of multi-layered mucosal epithelia and lower connective tissue
and were similar to normal middle ear mucosa. This result indicates that tissue
engineered mucosal cell sheets would be useful to minimize complications after
surgical operations in the middle ear and future clinical applications are
expected. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 25846101
TI - Using travel socialization and underlying motivations to better understand
motorcycle usage in Taiwan.
AB - This study introduces self-determination theory (SDT) to refine previous models
of vehicle usage motivation. We add travel socialization theory regarding
parental influence on vehicle usage to enhance previous structural models
describing motorcycle usage behavior. Our newly developed model was empirically
verified in a sample of 721 motorcycle users in Taiwan. In addition to
instrumental, symbolic, and affective motivations, perceived parental attitudes
(PPAs) towards motorcycle riding were found to have a significant effect on
individuals' motorcycle use habits. Additionally, participants who perceived
their parents to have more positive attitudes toward motorcycles were found to
have more experience being chauffeured on motorcycles by their parents. Based on
these results, we suggest means to confront the challenges brought on by the
rapid growth of motorcycle usage, especially serious motorcycle traffic
accidents. These results improve our understanding motorcycle usage in Taiwan and
can be used by transportation professionals who are seeking solutions to the
rapid growth of motorcycle usage.
PMID- 25846102
TI - An experimental study of factors associated with driver frustration and
overtaking intentions.
AB - This study examined directly the impact of various factors associated with
driving on 'A-class' roads in the United Kingdom (specifically length of platoon,
proportion of heavy goods vehicles (HGVs), speed and opportunities for
overtaking) on self-reported frustration and overtaking intentions. The impact of
situational variables (being under time pressure, and time behind a slower moving
platoon) were also examined, as was the association between frustration and self
reported overtaking intentions. 183 members of the public from the areas around
Perth and Inverness, Scotland took part in the study. Participants viewed
simulated 'driver's viewpoint' clips representing all the combinations of the
experimental variables (except time pressure, which was a between-groups
variable, and time behind platoon, which was examined separately in four specific
clips). After each clip, participants responded on a paper questionnaire as to
the level of frustration they would feel for a given clip, and the likelihood
that at some point during the clip they would have attempted an overtake
manoeuvre. The findings show that the links between traffic variables such as
speed and platoon length, and behaviourally-relevant variables such as
frustration and overtaking intentions, are not simple. Although there are broad
and predictable effects of speed and platoon length (lower speeds and longer
platoons leading to greater frustration) these are mediated by other variables,
and it is not always the case that more frustration leads to more intention to
overtake. Analysis of driver attitudes identified three clusters (low, medium and
high risk drivers) and suggests that higher risk drivers' levels of frustration
are more affected by situational changes than those of lower risk drivers.
PMID- 25846103
TI - Attenuation of renovascular hypertension by cyclooxygenase-2 inhibitor partly
through ANP release.
AB - Angiotensin II (Ang II) is an important inflammatory mediator. Ang II induces
cyclooxygenase-2 (COX-2) expression and prostaglandin F2alpha release followed by
cardiac hypertrophy. Inhibition of COX-2 may modulate high blood pressure but
controversy still exists. The aim of this study was to determine the role of COX
2 in the regulation of blood pressure and to define the mechanisms in two kidney
one-clip hypertensive (2K1C) rats. Chronic treatment with nimesulide or NS-398 (5
mg/kg/day) for 3 weeks lowered high blood pressure and cardiac hypertrophy with
decreased expression levels of cardiac hypertrophy markers [atrial natriuretic
peptide (ANP), brain natriuretic peptide (BNP)], Ang type 1 receptor, urotensin
II, and urotensin II receptor in 2K1C rats. Plasma level of ANP was markedly
increased and plasma levels of Ang II and aldosterone were decreased by treatment
with nimesulide or NS-398. In both in vitro and in vivo experiments, nimesulide
or NS-398 augmented ANP release in 2K1C rats. The inhibitory effect of NS-398 on
blood pressure was attenuated by the pretreatment with natriuretic peptide
receptor-A (NPR-A) antagonist (A71915, 30 MUg/kg/day). These results suggest that
chronic treatment with nimesulide or NS-398 attenuated hypertension and cardiac
hypertrophy partly through ANP release in 2K1C rats.
PMID- 25846104
TI - Fluorogenic sequencing using halogen-fluorescein-labeled nucleotides.
AB - Fluorogenic sequencing is a sequencing-by-synthesis technology that combines the
advantages of pyrosequencing and fluorescence detection. With native duplex DNA
as the major product, we employ polymerase to incorporate the complement- arily
matched terminal phosphate-labeled fluorogenic nucleotides into the DNA template
and release halogen-fluorescein as the reporter. This red-emitting fluorophore
successfully avoids spectral overlap with the autofluorescence background of the
flow chip. We fully characterized the enzymatic reaction kinetics of the new
substrates, and performed a 35-base sequencing experiment with 60 reaction
cycles. Our achievement expands the substrate repertoire for fluorogenic
sequencing, and extends the spectral range to obtain better signal-to-background
performance.
PMID- 25846105
TI - Acceleration of thiol additive-free native chemical ligation by intramolecular S
> S acyl transfer.
AB - Peptide-mercaptopropionylcysteine (MPA-Cys) thioesters show a surprisingly high
reactivity in native chemical ligation (NCL) and allow thiol-additive free
reactions. This facilitates sequential NCL reactions and ligation-desulfurization
reactions in one-pot formats. The synthetic utility is demonstrated by the
synthesis of a SH3 domain.
PMID- 25846106
TI - Establishment and characterization of a novel VEGF-producing HHV-8-unrelated PEL
like lymphoma cell line, OGU1.
AB - Primary effusion lymphoma (PEL) is a rare B-cell lymphoma subtype that is
characterized by lymphomatous effusion without the presence of masses, and it
typically occurs in human immunodeficiency virus (HIV)-infected individuals.
Lymphoma cells are universally positive for human herpesvirus 8 (HHV-8).
Recently, a cavity-based effusion lymphoma that is similar to PEL without HHV-8
infection, called HHV-8-unrelated PEL-like lymphoma, has been reported in non-HIV
infected individuals. However, the pathophysiology of this lymphoma is largely
undefined. We established a novel B-cell line OGU1 derived from a patient with
HHV-8-unrelated PEL-like lymphoma. Notably, OGU1 cells produced vascular
endothelial growth factor (VEGF) and expressed VEGF receptor 1, whose inhibitors
retarded cell growth. Because VEGF acts as a vascular permeability and growth
factor, it could play a role, at least in part, in the pathogenesis of this
unique lymphoma. Thus, the OGU1 cell line is useful for the investigation of HHV
8-unrelated PEL-like lymphoma.
PMID- 25846107
TI - Membrane-intercalating conjugated oligoelectrolytes: impact on bioelectrochemical
systems.
AB - Conjugated oligoelectrolytes (COEs), molecules that are defined by a pi
delocalized backbone and terminal ionic pendant groups, have been previously
demonstrated to effectively reduce charge-injection/extraction barriers at
metal/organic interfaces in thin-film organic-electronic devices. Recent studies
demonstrate a spontaneous affinity of certain COEs to intercalate into, and align
within, lipid bilayers in an ordered orientation, thereby allowing modification
of membrane properties and the functions of microbes in bioelectrochemical and
photosynthetic systems. Several reports have provided evidence of enhanced
current generation and bioproduction. Mechanistic approaches suggest that COEs
influence microbial extracellular electron transport to abiotic electrode
surfaces via more than one proposed pathway, including direct electron transfer
and meditated electron transfer. Molecular dynamics simulations as a function of
molecular structure suggest that insertion of cationic COEs results in membrane
thinning as the lipid phosphate head groups are drawn toward the center of the
bilayer. Since variations in molecular structures, especially the length of the
conjugated backbone, distribution of ionic groups, and hydrophobic substitutions,
show an effect on their antimicrobial properties, preferential cell localization,
and microbial selection, it is promising to further design novel membrane
intercalating molecules based on COEs for practical applications, including
energy generation, environmental remediation, and antimicrobial treatment.
PMID- 25846113
TI - Correction and optimization of a T2-based approach to map blood oxygenation in
small cerebral veins.
AB - PURPOSE: Cerebral venous blood oxygenation (Yv ) is an important biomarker in
brain physiology and function. The present study proposes a procedure to provide
a quantitative map of the brain's intravascular Yv. THEORY AND METHODS: The
method is based on a pulse sequence, T2 -Relaxation-Under-Phase-Contrast (TRU-PC)
MRI, with postprocessing approaches to correct eddy-current effects. A complete
scan protocol consists of four TRU-PC scans sensitized to large and small vessels
with anterior-posterior and foot-head flow-encoding directions, and the data are
analyzed conjunctively. Eddy-current correction was performed by fitting the
tissue phase to a hyperplane, and then subtracting the eddy-current phase from
the measured vessel phase. The reproducibility of the Yv-maps was examined in
five participants. Sensitivity of the Yv map to a caffeine challenge was studied
in another five participants. RESULTS: Removal of eddy-current induced artifact
allowed for the correction of T2 measurements, as demonstrated in vivo and with
simulation. A Yv-map depicting all vessels in the slice can be obtained with the
proposed protocol. Test-retest variability of the Yv -map was 3.7 +/- 1.2%. Yv
reduction can be reliably detected (P < 0.001) following the caffeine ingestion.
CONCLUSION: With the proposed TRU-PC protocol and eddy-current correction
procedure, an accurate, vessel-specific Yv map of the human brain can be
obtained.
PMID- 25846115
TI - Ups and Downs in Auditory Development: Preschoolers' Sensitivity to Pitch Contour
and Timbre.
AB - Much research has explored developing sound representations in language, but less
work addresses developing representations of other sound patterns. This study
examined preschool children's musical representations using two different tasks:
discrimination and sound-picture association. Melodic contour--a musically
relevant property--and instrumental timbre, which is (arguably) less musically
relevant, were tested. In Experiment 1, children failed to associate cartoon
characters to melodies with maximally different pitch contours, with no advantage
for melody preexposure. Experiment 2 also used different-contour melodies and
found good discrimination, whereas association was at chance. Experiment 3
replicated Experiment 2, but with a large timbre change instead of a contour
change. Here, discrimination and association were both excellent. Preschool-aged
children may have stronger or more durable representations of timbre than
contour, particularly in more difficult tasks. Reasons for weaker association of
contour than timbre information are discussed, along with implications for
auditory development.
PMID- 25846114
TI - Dietary nitrate improves sprint performance and cognitive function during
prolonged intermittent exercise.
AB - It is possible that dietary nitrate (NO3 (-)) supplementation may improve both
physical and cognitive performance via its influence on blood flow and cellular
energetics. PURPOSE: To investigate the effects of dietary NO3 (-)
supplementation on exercise performance and cognitive function during a prolonged
intermittent sprint test (IST) protocol, which was designed to reflect typical
work patterns during team sports. METHODS: In a double-blind randomised crossover
study, 16 male team-sport players received NO3 (-)-rich (BR; 140 mL day(-1); 12.8
mmol of NO3 (-)), and NO3 (-)-depleted (PL; 140 mL day(-1); 0.08 mmol NO3 (-))
beetroot juice for 7 days. On day 7 of supplementation, subjects completed the
IST (two 40-min "halves" of repeated 2-min blocks consisting of a 6-s "all-out"
sprint, 100-s active recovery and 20 s of rest), on a cycle ergometer during
which cognitive tasks were simultaneously performed. RESULTS: Total work done
during the sprints of the IST was greater in BR (123 +/- 19 kJ) compared to PL
(119 +/- 17 kJ; P < 0.05). Reaction time of response to the cognitive tasks in
the second half of the IST was improved in BR compared to PL (BR first half: 820
+/- 96 vs. second half: 817 +/- 86 ms; PL first half: 824 +/- 114 vs. second
half: 847 +/- 118 ms; P < 0.05). There was no difference in response accuracy.
CONCLUSIONS: These findings suggest that dietary NO3 (-) enhances repeated sprint
performance and may attenuate the decline in cognitive function (and specifically
reaction time) that may occur during prolonged intermittent exercise.
PMID- 25846116
TI - miR-34c plays a role of tumor suppressor in HEC-1-B cells by targeting E2F3
protein.
AB - Endometrial carcinoma (EC) is a common malignancy of the female genital tract
with a poor prognosis. It has been reported that miR-34c is significantly reduced
in EC, but research concerning its function in EC is rare. In the present study,
the expression of miR-34c was upregulated in the EC cell line, HEC-1-B, by
transfecting the cells with hsa-miR-34c-5p mimics. Then, after determining the
transfection efficiency by RT-qPCR, we analyzed the effects of miR-34c on the HEC
1-B cells. We found that overexpression of miR-34c significantly inhibited cell
proliferation, colony formation, migration and invasion and induced cell cycle
arrest and apoptosis. Finally, western blot analysis demonstrated that the
expression of E2F3 was reduced after upregulation of the expression of miR-34c in
the HEC-1-B cells, and the effects of miR-34c are likely associated with the
reduction in E2F3 protein. In conclusion, our study demonstrated that miR-34c
plays a role of tumor suppressor in HEC-1-B cells, and E2F3 protein may be a
target of miR-34c.
PMID- 25846117
TI - Laryngocele: an unusual presentation.
PMID- 25846118
TI - Solitary neurofibroma originating from the posterior nasal septum: Transnasal
endoscopic resection.
AB - INTRODUCTION: The head and neck region is one of the locations of neurogenic
tumors such as neurofibroma. Although mostly associated with neurofibromatosis,
it can be solitary. The present study reports a very rare case of solitary
neurofibroma originating from the posterior nasal septum. CASE PRESENTATION: A 48
year-old female presented with tumor in the right nasal cavity. The tumor,
originating in the posterior nasal septum, extended to the posterior sinuses and
nasopharynx. Following endoscopic and radiological assessment, the tumor was
resected by transnasal endoscopic surgery. Histological examination showed the
tumor to be a neurofibroma. At 14months' follow-up, there was no recurrence.
DISCUSSION AND CONCLUSIONS: However rare, solitary neurofibroma must be
considered in the differential diagnosis of unilateral benign tumor involving
nasal and paranasal sinuses. A transnasal endoscopic approach should be
considered for treatment.
PMID- 25846119
TI - Giant tumour of the parotid gland.
PMID- 25846120
TI - Value and limits of non-robotic transoral oropharyngectomy for local control of
T1-2 invasive squamous cell carcinoma of the tonsillar fossa.
AB - BACKGROUND: An analysis of the value and limits of non-robotic transoral
oropharyngectomy for local control of T1-2 squamous cell carcinoma of the
tonsillar fossa. METHODS: A retrospective series of 111 T1 and 133 T2 (N0: 129;
N1: 52; N2: 53; N3: 10). Induction chemotherapy and postoperative radiation
therapy were used in 63.5% and 29.5% of cases, respectively. Actuarial analysis
of local failure, impact of various variables upon local failure and consequences
of local failure upon other oncological events and survival are documented.
RESULTS: The 5-year actuarial local failure estimate was 10.4% and 14.2% for T1
and T2 tumors, respectively. The 5-year actuarial local failure estimate was
significantly reduced when resection margins were safe or yielded dysplasia
(P=0.008) and when induction chemotherapy achieved complete histologic regression
(P=0.013). Salvage treatment achieved a 97.2% and 93.2% overall local control
rate in T1 and T2 tumors, respectively. The 5-year actuarial nodal failure
estimate was 35.1% in patients with local failure versus 10.8% without
(P=0.0001). The 5-year actuarial metachronous second primary estimate was 7% in
patients with local failure versus 33.2% without (P=0.016). The impact of local
failure on survival (5-year actuarial survival estimate: 67.3% without and 46.4%
with local failure) was not significant. CONCLUSION: In T1-2 squamous cell
carcinoma of the tonsillar fossa, non-robotic transoral oropharyngectomy appeared
to be highly effective in terms of local control. The high incidence of head and
neck metachronous second primaries further advocates the use of this treatment
option in order to reserve radiation therapy to such cases.
PMID- 25846121
TI - Gorillas with white sclera: A naturally occurring variation in a morphological
trait linked to social cognitive functions.
AB - Human eye morphology is considered unique among the primates in that humans
possess larger width/height ratios (WHR), expose a greater amount of visible
sclera (SSI; width of exposed eyeball/width of visible iris), and critically,
have a white sclera due to a lack of pigmentation. White sclera in humans
amplifies gaze direction, whereas the all-dark eyes of apes are hypothesized to
conceal gaze from others. This study examines WHR and SSI in humans (N = 13) and
gorillas (N = 85) engaged in direct and averted gazes and introduces a
qualitative assessment of sclera color to evaluate variations in sclera
pigmentation. The results confirm previous findings that humans possess a larger
WHR than gorillas but indicate that humans and gorillas display similar amounts
of visible sclera. Additionally, 72% (N = 124) of gorilla eyes in this sample
deviated from the assumed all-dark eye condition. This questions whether gaze
camouflage is the primary function of darkened sclera in non-human primates or
whether other functional roles can be ascribed to the sclera, light or dark. We
argue that white sclera evolved to amplify direct gazes in humans, which would
have played a significant role in the development of ostensive communication,
which is communication that both shows something and shows the intention to show
something. We conclude that the horizontal elongation of the human eye, rather
than sclera color, more reliably distinguishes human from great ape eyes,
represented here by gorillas.
PMID- 25846122
TI - Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk:
findings from the Colorectal Cancer Family Registry.
AB - Diets high in red meat and processed meats are established colorectal cancer
(CRC) risk factors. However, it is still not well understood what explains this
association. We conducted comprehensive analyses of CRC risk and red meat and
poultry intakes, taking into account cooking methods, level of doneness,
estimated intakes of heterocyclic amines (HCAs) that accumulate during meat
cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We
analyzed food frequency and portion size data including a meat cooking module for
3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620
unaffected population-based controls, recruited into the CRC Family Registry.
Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables
were estimated using generalized estimating equations. We found no evidence of an
association between total nonprocessed red meat or total processed meat and CRC
risk. Our main finding was a positive association with CRC for pan-fried
beefsteak (P(trend) < 0.001), which was stronger among MMR deficient cases
(heterogeneity P = 0.059). Other worth noting associations, of borderline
statistical significance after multiple testing correction, were a positive
association between diets high in oven-broiled short ribs or spareribs and CRC
risk (P(trend) = 0.002), which was also stronger among MMR-deficient cases, and
an inverse association with grilled hamburgers (P(trend) = 0.002). Our results
support the role of specific meat types and cooking practices as possible sources
of human carcinogens relevant for CRC risk.
PMID- 25846123
TI - Abstinence and relapse among smokers who use varenicline in a quit attempt-a
pooled analysis of randomized controlled trials.
AB - BACKGROUND AND AIMS: Varenicline increases the likelihood of long-term abstinence
following a quit attempt. It has been suggested that (1) part of its benefit
arises from 'recruiting into abstinence' smokers who are not able to stop on the
target quit date and (2) there may be a higher rate of relapse after treatment.
This study addressed these issues. METHODS: Meta-analyses of data from randomized
controlled trials (RCTs) of varenicline identified from the 2012 Cochrane review
of nicotine receptor partial agonists for smoking cessation were used to compare
the abstinence and relapse patterns on active drug and placebo. Studies of
varenicline compared with placebo in adult daily smokers with longest follow-up
at either 6 or 12 months and with at least three follow-ups in the first month
were included. Biochemically verified abstinence rates at each of six follow-up
time-points (2, 3, 4, 12, 24 and 52 weeks) were pooled for studies reporting
point prevalence abstinence. Biochemically verified abstinence rates at three
follow-up time-periods (9-12 weeks, 9-24 weeks and 9-52 weeks) were pooled for
studies reporting continuous abstinence. Random effects meta-analysis was used to
estimate pooled proportions with 95% confidence intervals. RESULTS: Nineteen RCTs
were included. In varenicline-treated participants, point-prevalence abstinence
increased by 22 percentage points from week 2 [32%: 95% confidence interval (CI)
= 25-40%] to week 12 (54%: 95% CI = 48-61%). The increase was 8 percentage points
in the placebo group: 16% (95% CI = 11-21%) to 24% (95% CI = 17-33%). In
varenicline-treated participants the relapse from weeks 9-12 to week 52 was 55%:
49% abstinent in weeks 9-12 (95% CI = 45-53%) versus 22% at week 52 (95% CI = 19
25%). In placebo-treated participants it was 53%: 17% (95% CI = 13-25%) in weeks
9-12 versus 8% (95% CI = 6-12%) at week 52. CONCLUSIONS: Varenicline recruits
smokers into abstinence following the target quit date to a greater extent than
placebo. Relapse rates from end of treatment to 52 weeks are similar in
varenicline- and placebo-treated smokers.
PMID- 25846124
TI - Deletion analysis of Streptococcus pneumoniae late competence genes distinguishes
virulence determinants that are dependent or independent of competence induction.
AB - The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for
genetic transformation. During competence development, the alternative sigma
factor ComX is activated, which in turn, initiates transcription of 80 'late'
competence genes. Interestingly, only 16 late genes are essential for genetic
transformation. We hypothesized that these late genes that are dispensable for
competence are beneficial to pneumococcal fitness during infection. These late
genes were systematically deleted, and the resulting mutants were examined for
their fitness during mouse models of bacteremia and acute pneumonia. Among these,
14 late genes were important for fitness in mice. Significantly, deletion of some
late genes attenuated pneumococcal fitness to the same level in both wild-type
and ComX-null genetic backgrounds, suggesting that the constitutive baseline
expression of these genes was important for bacterial fitness. In contrast, some
mutants were attenuated only in the wild-type genetic background but not in the
ComX-null background, suggesting that specific expression of these genes during
competence state contributed to pneumococcal fitness. Increased virulence during
competence state was partially caused by the induction of allolytic enzymes that
enhanced pneumolysin release. These results distinguish the role of basal
expression versus competence induction in virulence functions encoded by ComX
regulated late competence genes.
PMID- 25846125
TI - Does dose matter in reducing gestational weight gain in exercise interventions? A
systematic review of literature.
AB - OBJECTIVES: The purpose of this review was to examine the relationship between
exercise dose and reductions in weight gain during pregnancy in exercise
interventions. DESIGN: Systematic literature review. METHODS: Four electronic
research databases (PubMed, Web of Science, CINAHL, and Academic Search Premiere)
were used to identify exercise interventions conducted with pregnant women.
Eligible articles must have satisfied the following criteria: inclusion of a
control condition, exercise as a major intervention component, weight gain
measured and reported for each experimental condition, description of exercise
dose (frequency, intensity and duration), and utilized an adequate number of
control conditions to assess independent effects of exercise on weight gain.
RESULTS: The literature search identified 4837 articles. Of these, 174 abstracts
were screened and 21 intervention studies (18 exercise-only, 3 exercise/diet)
were eligible for review. Only 38% of the interventions achieved statistically
significant reductions in gestational weight gain. Successful interventions
possessed higher adherence and lower attrition rates and were predominantly
conducted among normal weight populations. No clear patterns or consistencies of
exercise dose and reductions in weight gain were evident. CONCLUSIONS: An
exercise dose associated with reductions in weight gain was unquantifiable among
these interventions. Adherence and retention rates were strong contributors to
the success of exercise interventions on gestational weight gain. It is strongly
suggested that future researchers investigate methods to increase adherence and
compliance, especially among overweight and obese women, and utilize objective
measurement tools to accurately evaluate exercise dose performed by the
participants and the impact on body composition and weight gain.
PMID- 25846126
TI - More children more active: Tailored playgrounds positively affect physical
activity levels amongst youth.
AB - OBJECTIVES: Overall physical activity (PA) of children is low, and the physical
inactivity problem is highest in deprived neighborhoods. The overall goal of the
Richard Krajicek Foundation is to provide children in deprived neighborhoods with
safe public playgrounds that stimulate daily PA. This study investigates whether
Krajicek playgrounds are associated with higher usage and intensity of PA
compared to control playgrounds during playground use amongst children. DESIGN:
Cross-sectional observational study. METHODS: Ten Krajicek and ten control
playgrounds in The Netherlands were matched for neighborhood and playground
characteristics. Usage and intensity of PA at the playgrounds were measured using
direct observation (SOPLAY). Trained observers collected PA data after-school
time on weekdays and weekend days. Multilevel regression analyses were performed
to analyze the difference in usage and intensity of PA between control and
Krajicek playgrounds. RESULTS: Krajicek playgrounds were significantly less often
empty compared to control playgrounds (12% vs. 29%). In addition, there was a
statistically significant difference in the number of boys observed on the
Krajicek playgrounds (14 vs. 9, OR 1.8). Across all categories differences in
playground PA were found with an average of 13% of the children on Krajicek
playgrounds engaged in moderate-to-vigorous physical activity (MVPA) compared to
10% on control playgrounds. Energy-expenditure (EE) per child was higher on
Krajicek playgrounds across all groups (B.006). CONCLUSIONS: Krajicek playgrounds
are positively associated with higher usage and PA intensity compared to control
playgrounds. Our results indicate that Krajicek playgrounds can benefit PA of
children living in deprived neighborhoods during playground play.
PMID- 25846128
TI - Syntheses, structures, and magnetic properties of three new cyano-bridged
complexes based on the [Mn(CN)6](3-) building block.
AB - With three pentadentate macrocyclic ligands, three new [Mn(CN)6](3-) based
complexes, [Mn(L(N3O2))(H2O)]2[Mn(CN)6](ClO4).3H2O (1), {[Mn(L(N5))]3[Mn(CN)6]2}n
(2) and {[Mn(L(N5Me))]3[Mn(CN)6]2}n.10nH2O (3) (L(N3O2) = 2,13-dimethyl-6,9-dioxa
3,12,18-triazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene, L(N5) = 2,13
dimethyl-3,6,9,12,18-pentaazabicyclo-[12.3.1]octadeca-1(18),2,12,14,16-pentaene,
L(N5Me) = 2,6-bis[1-(2-(N-methylamino)ethylimino)ethyl]-pyridine), have been
synthesized and characterized structurally and magnetically. The structure of 1
was found to be a linear Mn2(II)Mn(III) trinuclear cluster with two Mn(II)
capping groups and one Mn(III) ion connected via two trans-cyano groups. In
contrast, compounds 2 and a3 re cyano-bridged 2D networks. Magnetic investigation
revealed antiferromagnetic coupling between the Mn(III) and Mn(II) ions via the
bridging cyanide groups. Complex 1 showed paramagnetic behavior down to 2.0 K
with no sign of SMM behavior. The magnetic coupling constant of J = -1.63 cm(-1)
with the Hamiltonian H = -2J(S(Mn(III)).SMn(II)1 + SMn(III).S(Mn(II)2)) was
obtained from the fitting of the magnetic susceptibility. For 2 and 3,
ferrimagnetic ordering was observed with magnetic phase transition temperatures
(Tc) being 7.5 K and 7.0 K, respectively. These compounds are rare examples of a
small number of [Mn(CN)6](3-) based magnetic materials.
PMID- 25846129
TI - Total tract nutrient digestion and milk fatty acid profile of dairy cows fed
diets containing different levels of whole raw soya beans.
AB - Whole oilseeds such as soya beans have been utilized in dairy rations to supply
additional fat and protein. However, antinutritional components contained in soya
beans, such as trypsin inhibitors and haemagglutinins (lectins) may alter
digestibility of nutrients and consequently affect animal performance. The
objective of the present experiment was to quantify the effect of different
levels of whole raw soya beans in diets of dairy cows on nutrient intake, total
tract digestion, nutrient balances and milk yield and composition. Sixteen mid to
late-lactation cows (228 +/- 20 days in milk; mean +/- SD) were used in four
replicated 4 * 4 Latin square design experiment with 21-d periods. Cows were
assigned to each square according to milk yield and DIM. The animals were
randomly allocated to treatments: control (without soya beans addition; CO), WS9,
WS18 and WS27, with addition of 9%, 18% and 27% of whole raw soya bean in diet on
a dry matter (DM) basis respectively. All diets contained identical forage and
concentrate components and consisted of maize silage and concentrate based on
ground corn and soya beans at a ratio of 60:40. There were no differences in OM,
CP, NDF and NEL intakes (kg/day and MJ/day) among the treatments (p > 0.05).
However, DM and NFC intakes were negatively affected (p = 0.04 and p < 0.01,
respectively) and ether extract (EE) intake was positively affected (p < 0.01).
Total tract digestion increased linearly with whole raw soya beans for EE (p <
0.01) and NDF (p = 0.01). The excretion (kg/day) of digested soya beans grains
increased linearly according to addition of whole raw soya beans. However, the
nutritive characteristics of excreted grains were not altered. Milk (kg), milk
lactose (kg) and protein (kg) yield decreased linearly (p < 0.01, p < 0.01 and p
= 0.04, respectively) milk fat content (%) increased linearly (p < 0.01) with
whole raw soya beans inclusion. Increasing addition of whole raw soya beans
affected milk fatty acid profile with a linear decrease of cis-9-trans 11CLA and
total saturated FA; and linear increase of total unsaturated and C18:3 FA. Energy
balance was positively affected (p = 0.03) by whole raw soya beans as well as
efficiency of NEL milk/DE intake (p = 0.02). Nitrogen balance and microbial
protein synthesis were not affected by whole raw soya beans. Increasing doses of
whole raw soya beans decreased dry matter intake and milk yield, however, led to
an increase of unsaturated acids in milk and higher milk fat concentration.
PMID- 25846127
TI - A Low Protein Binding Cationic Poly(2-oxazoline) as Non-Viral Vector.
AB - Developing safe and efficient non-viral gene delivery systems remains a major
challenge. We present a new cationic poly(2-oxazoline) (CPOx) block copolymer for
gene therapy that was synthesized by sequential polymerization of non-ionic 2
methyl-2-oxazoline and a new 2-oxazoline monomer, 2-(N-methyl, N-Boc-amino)
methyl-2-oxazoline, followed by deprotection of the pendant secondary amine
groups. Upon mixing with plasmid DNA (pDNA), CPOx forms small (diameter ~80 nm)
and narrowly dispersed polyplexes (PDI <0.2), which are stable upon dilution in
saline and against thermal challenge. These polyplexes exhibited low plasma
protein binding and very low cytotoxicity in vitro compared to the polyplexes of
pDNA and poly(ethylene glycol)-b-poly(L-lysine) (PEG-b-PLL). CPOx/pDNA polyplexes
at N/P = 5 bound considerably less plasma protein compared to polyplexes of PEG-b
PLL at the same N/P ratio. This is a unique aspect of the developed polyplexes
emphasizing their potential for systemic delivery in vivo. The transfection
efficiency of the polyplexes in B16 murine melanoma cells was low after 4 h, but
increased significantly for 10 h exposure time, indicative of slow
internalization of polyplexes. Addition of Pluronic P85 boosted the transfection
using CPOx/pDNA polyplexes considerably. The low protein binding of CPOx/pDNA
polyplexes is particularly interesting for the future development of targeted
gene delivery.
PMID- 25846130
TI - Appraising the methodological quality of cadaveric studies: validation of the
QUACS scale.
AB - Although systematic reviews are conducted in the field of anatomical research, no
instruments exist for the assessment of study quality. Thus, our objective was to
develop a valid tool that reliably assesses the methodological quality of
observational cadaveric studies. The QUACS scale (QUality Appraisal for Cadaveric
Studies) was developed using an expert consensus process. It consists of a 13
item checklist addressing the design, conduct and report of cadaveric dissection
studies. To evaluate inter-rater reliability, a blinded investigator obtained an
initial pool of 120 observational cadaveric studies. Sixty-eight of them were
selected randomly according to sample size calculations. Three independent
researchers rated each publication by means of the QUACS scale. The reliability
of the total score was estimated using the intraclass correlation coefficient
(ICC). To assess agreement among individual items, margin-free kappa values were
calculated. For construct validity, two experts (an anatomist and an experienced
physician) categorized the quality of 15 randomly selected studies as 'excellent'
(4 points), 'moderate to good' (3 points), poor to moderate' (2 points) or 'poor'
(1 point). Kendall's tau rank correlation was used to compare the expert ratings
with the scores on the QUACS scale. An evaluation of feasibility was carried out
during the reliability analysis. All three raters recorded the duration of
quality appraisal for each article. Means were used to describe average time
exposure. The ICC for the total score was 0.87 (95% confidence interval: 0.82
0.92; P < 0.0001). For individual items, margin-free kappa values ranged between
0.56 and 0.96 with an agreement of 69-97% among the three raters. Kendall's tau B
coefficient of the association between expert ratings and the results obtained
with the QUACS scale was 0.69 (P < 0.01). Required rating time per article was
5.4 +/- 1.6 min. The QUACS scale is highly reliable and exhibits strong construct
validity. Thus, it can confidently be applied in assessing the methodological
quality of observational dissection studies.
PMID- 25846131
TI - Characterization of a 520 kb deletion on chromosome 15q26.1 including ST8SIA2 in
a patient with behavioral disturbance, autism spectrum disorder, and epilepsy:
additional information.
PMID- 25846133
TI - Stereogenic alpha-carbons determine the shape and topology of [13]
macrodilactones.
AB - The synthesis and characterization of new [13]-macrodilactones substituted at
stereogenic centers alpha- to the carbonyl are reported. When one center is
substituted, it directs the topology of the macrocycle; when two centers are
substituted, both the shape and the topology are influenced. The findings
indicate that the number and configuration of alpha-centers fine-tune macrocyclic
structure.
PMID- 25846132
TI - Spinal muscular atrophy functional composite score: A functional measure in
spinal muscular atrophy.
AB - INTRODUCTION: With clinical trials underway, our objective was to construct a
composite score of global function that could discriminate among people with
spinal muscular atrophy (SMA). METHODS: Data were collected from 126 participants
with SMA types 2 and 3. Scores from the Hammersmith Functional Motor Scale
Expanded and Upper Limb Module were expressed as a percentage of the maximum
score and 6-minute walk test as percent of predicted normal distance. A principal
component analysis was performed on the correlation matrix for the 3 percentage
scores. RESULTS: The first principal component yielded a composite score with
approximately equal weighting of the 3 components and accounted for 82% of the
total variability. The SMA functional composite score, an unweighted average of
the 3 individual percentage scores, correlated almost perfectly with the first
principal component. CONCLUSIONS: This combination of measures broadens the
spectrum of ability that can be quantified in type 2 and 3 SMA patients.
PMID- 25846134
TI - Acid sensitivity of the spinal dorsal root ganglia C-fiber nociceptors
innervating the guinea pig esophagus.
AB - BACKGROUND: Gastroesophageal reflux can cause high acidity in the esophagus and
trigger heartburn and pain. However, because of the esophageal mucosal barrier,
the acidity at the nerve terminals of pain-mediating C-fibers in esophageal
mucosa is predicted to be substantially lower. We hypothesized that the
esophageal dorsal root ganglia (DRG) C-fibers are activated by mild acid
(compared to acidic reflux), and express receptors and ion channels highly
sensitive to acid. METHODS: Extracellular single unit recordings of activity
originating in esophageal DRG C-fiber nerve terminals were performed in the
innervated esophagus preparation ex vivo. Acid was delivered in a manner that
bypassed the esophageal mucosal barrier. The expression of mRNA for selected
receptors in esophagus-specific DRG neurons was evaluated using single cell RT
PCR. KEY RESULTS: Mild acid (pH = 6.5-5.5) activated esophageal DRG C-fibers in a
pH-dependent manner. The response to mild acid at pH = 6 was not affected by the
TRPV1 selective antagonist iodo-resiniferatoxin. The majority (70-95%) of
esophageal DRG C-fiber neurons (TRPV1-positive) expressed mRNA for acid sensing
ion channels (ASIC1a, ASIC1b, ASIC2b, and/or ASIC3), two-pore-domain (K2P)
potassium channel TASK1, and the proton-sensing G-protein coupled receptor OGR1.
Other evaluated targets (PKD2L1, TRPV4, TASK3, TALK1, G2A, GPR4, and TDAG8) were
expressed rarely. CONCLUSIONS & INFERENCES: Guinea pig esophageal DRG C-fibers
are activated by mild acid via a TRPV1-independent mechanism, and express mRNA
for several receptors and ion channels highly sensitive to acid. The high acid
sensitivity of esophageal C-fibers may contribute to heartburn and pain in
conditions of reduced mucosal barrier function.
PMID- 25846136
TI - Differential dynamics of RAS isoforms in GDP- and GTP-bound states.
AB - RAS subfamily proteins regulates cell growth promoting signaling processes by
cycling between active (GTP-bound) and inactive (GDP-bound) states. Different RAS
isoforms, though structurally similar, exhibit functional specificity and are
associated with different types of cancers and developmental disorders.
Understanding the dynamical differences between the isoforms is crucial for the
design of inhibitors that can selectively target a particular malfunctioning
isoform. In this study, we provide a comprehensive comparison of the dynamics of
all the three RAS isoforms (HRAS, KRAS, and NRAS) using extensive molecular
dynamics simulations in both the GDP- (total of 3.06 MUs) and GTP-bound (total of
2.4 MUs) states. We observed significant differences in the dynamics of the
isoforms, which rather interestingly, varied depending on the type of the
nucleotide bound and the simulation temperature. Both SwitchI (Residues 25-40)
and SwitchII (Residues 59-75) differ significantly in their flexibility in the
three isoforms. Furthermore, Principal Component Analysis showed that there are
differences in the conformational space sampled by the GTP-bound RAS isoforms. We
also identified a previously unreported pocket, which opens transiently during MD
simulations, and can be targeted to regulate nucleotide exchange reaction or
possibly interfere with membrane localization. Further, we present the first
simulation study showing GDP destabilization in the wild-type RAS protein. The
destabilization of GDP/GTP occurred only in 1/50 simulations, emphasizing the
need of guanine nucleotide exchange factors (GEFs) to accelerate such an
extremely unfavorable process. This observation along with the other results
presented in this article further support our previously hypothesized mechanism
of GEF-assisted nucleotide exchange.
PMID- 25846135
TI - The role of pyruvate hub enzymes in supplying carbon precursors for fatty acid
synthesis in photosynthetic microalgae.
AB - Photosynthetic microalgae are currently the focus of basic and applied research
due to an ever-growing interest in renewable energy resources. This review
discusses the role of carbon-unit supply for the production of acetyl-CoA, a
direct precursor of fatty acid biosynthesis and the primary building block of the
growing acyl chains for the purpose of triacylglycerol (TAG) production in
photosynthetic microalgae under stressful conditions. It underscores the
importance of intraplastidic acetyl-CoA generation for storage lipid
accumulation. The main focus is placed on two enzymatic steps linking the central
carbon metabolism and fatty acid synthesis, namely the reactions catalyzed by the
plastidic isoform of pyruvate kinase and the chloroplastic pyruvate dehydrogenase
complex. Alternative routes for plastidic acetyl-CoA synthesis are also reviewed.
A separate section is devoted to recent advances in functional genomics studies
related to fatty acid and TAG biosynthesis.
PMID- 25846137
TI - Small-Molecule Transport by CarO, an Abundant Eight-Stranded beta-Barrel Outer
Membrane Protein from Acinetobacter baumannii.
AB - Outer membrane (OM) beta-barrel proteins composed of 12-18 beta-strands mediate
cellular entry of small molecules in Gram-negative bacteria. Small OM proteins
with barrels of 10 strands or less are not known to transport small molecules.
CarO (carbapenem-associated outer membrane protein) from Acinetobacter baumannii
is a small OM protein that has been implicated in the uptake of ornithine and
carbapenem antibiotics. Here we report crystal structures of three isoforms of
CarO. The structures are very similar and show a monomeric eight-stranded barrel
lacking an open channel. CarO has a substantial extracellular domain resembling a
glove that contains all the divergent residues between the different isoforms.
Liposome swelling experiments demonstrate that full-length CarO and a "loop-less"
truncation mutant mediate small-molecule uptake at low levels but that they are
unlikely to mediate passage of carbapenem antibiotics. These results are
confirmed by biased molecular dynamics simulations that allowed us to
quantitatively model the transport of selected small molecules.
PMID- 25846138
TI - Exploring the chemical space of quorum sensing peptides.
AB - Quorum sensing peptides are signalling molecules that are produced by mainly gram
positive bacteria. These peptides can exert different effects, ranging from intra
and interspecies bacterial virulence to bacterial-host interactions. To better
comprehend these functional differences, we explored their chemical space,
bacterial species distribution and receptor-binding properties using multivariate
data analyses, with information obtained from the Quorumpeps database. The quorum
sensing peptides can be categorized into three main clusters, which, in turn, can
be divided into several subclusters: the classification is based on
characteristic chemical properties, including peptide size/compactness,
hydrophilicity/lipophilicity, cyclization and the presence of (unnatural) S
containing and aromatic amino acids. Most of the bacterial species synthesize
peptides located into one cluster. However, some Streptococcus, Stapylococcus,
Clostridium, Bacillus and Lactobacillus species produce peptides that are
distributed over more than one cluster, with the quorum sensing peptides of
Bacillus subtilis even occupying the total peptide space. The AgrC, FsrC and LamC
receptors are only activated by cyclic (thio)lacton or lactam quorum sensing
peptides, while the lipophilic isoprenyl-modified peptides solely bind the ComP
receptor in Bacillus species.
PMID- 25846139
TI - Nisin-induced expression of a recombinant antihypertensive peptide in dairy
lactic acid bacteria.
AB - OBJECTIVE: To improve the process for the production of milk-derived
antihypertensive peptides, including a 12-residue peptide (FFVAPFPECVGK) from
alphaS1-casein. RESULTS: A synthetic gene encoding this peptide was cloned within
the pediocin operon, replacing the nucleic acid sequence encoding the mature
pediocin peptide (papA) and resulting in a translational fusion between the
pediocin leader peptide and the 12-residue hypotensive (C-12) peptide. The
recombinant operon was subsequently cloned immediately downstream of the nisA
promoter to allow for inducible gene expression within Streptococcus thermophilus
ST128, Lactococcus lactis subsp. lactis ML3 and Lactobacillus casei C2. RT-PCR
was used to confirm recombinant gene expression in complex medium; and SDS-PAGE
analysis showed that the pediocin secretion machinery, encoded by papC and papD,
allowed for secretion of the recombinant peptide from both L. lactis ML3 and L.
casei C2 in a chemically defined medium. CONCLUSION: The use of a nisin as a
"food-grade" inducer molecule, and generally-regarded-as-safe LAB species
suggests that this system could be used for the production of functional food
ingredients.
PMID- 25846140
TI - Plate in situ hybridization (PISH) as a time and cost effective RNA expression
assay to study phenotypic heterogeneity in a population of cultured murine cells
at single cell resolution.
AB - OBJECTIVES: Regenerative medicine approaches using reprogrammed or
transdifferentiated cells require efficient single cell expression profiling to
analyze culture homogeneity for quality control and recipients' safety. RESULTS:
While antigen-antibody based systems have been developed for several proteins,
probing at the mRNA level allows for more flexibility, faster adaption to the
ever increasing new data from next generation sequencing and increased
specificity, especially for genes of conserved gene families. CONCLUSIONS: We
developed a time and cost effective expression profiling assay for monolayer cell
culture in 96-well plates based on RNA in situ hybridization, termed PISH, at
single cell resolution.
PMID- 25846141
TI - Single-arm phase II trial design under parametric cure models.
AB - The current practice of designing single-arm phase II survival trials is limited
under the exponential model. Trial design under the exponential model may not be
appropriate when a portion of patients are cured. There is no literature
available for designing single-arm phase II trials under the parametric cure
model. In this paper, a test statistic is proposed, and a sample size formula is
derived for designing single-arm phase II trials under a class of parametric cure
models. Extensive simulations showed that the proposed test and sample size
formula perform very well under different scenarios.
PMID- 25846142
TI - The nickel(II) complex of guanidinium phenyl porphyrin, a specific G-quadruplex
ligand, targets telomeres and leads to POT1 mislocalization in culture cells.
AB - With the aim of finding selective and biologically active G-quadruplex ligands,
modified porphyrin with bulky cationic substituents, meso-5,10,15,20-tetrakis(4
guanidinophenyl)porphyrin tetrahydrochloride, referred to as guanidinium phenyl
porphyrin, was prepared. The corresponding nickel(II) and cobalt(III) metallated
porphyrins were also synthesized. Interaction with quadruplexes was examined by
means of fluorescence resonance energy transfer melting and surface plasmon
resonance-based assays: the three compounds proved to bind to G-quadruplex DNA in
a similar and highly selective way. Guanidinium phenyl porphyrin and its
nickel(II) metallated derivative exhibit moderate cytotoxicity toward cells in
culture. Strikingly, the nickel porphyrin derivative was able to displace hPOT1
shelterin protein from telomeres in human cells. Nickel(II) guanidinium phenyl
porphyrin, a cationic bulky porphyrin is a powerful specific G-quadruplex DNA
ligand. It enters the cells and induces shelterin modification.
PMID- 25846143
TI - Intrinsic disorder and metal binding in UreG proteins from Archae
hyperthermophiles: GTPase enzymes involved in the activation of Ni(II) dependent
urease.
AB - Urease is a Ni(II) enzyme present in every domain of life, in charge for nitrogen
recycling through urea hydrolysis. Its activity requires the presence of two
Ni(II) ions in the active site. These are delivered by the concerted action of
four accessory proteins, named UreD, UreF, UreG and UreE. This process requires
protein flexibility at different levels and some disorder-to-order transition
events that coordinate the mechanism of protein-protein interaction. In
particular, UreG, the GTPase in charge of nucleotide hydrolysis required for
urease activation, presents a significant degree of intrinsic disorder, existing
as a conformational ensemble featuring characteristics that recall a molten
globule. Here, the folding properties of UreG were explored in Archaea
hyperthermophiles, known to generally feature significantly low level of
structural disorder in their proteome. UreG proteins from Methanocaldococcus
jannaschii (Mj) and Metallosphaera sedula (Ms) were structurally and functionally
analyzed by integrating circular dichroism, NMR, light scattering and enzymatic
assays. Metal-binding properties were studied using isothermal titration
calorimetry. The results indicate that, as the mesophilic counterparts, both
proteins contain a significant amount of secondary structure but maintain a
flexible fold and a low GTPase activity. As opposed to other UreGs, secondary
structure is lost at high temperatures (68 and 75 degrees C, respectively) with
an apparent two-state mechanism. Both proteins bind Zn(II) and Ni(II), with
affinities two orders of magnitude higher for Zn(II) than for Ni(II). No major
modifications of the average conformational ensemble are observed, but binding of
Zn(II) yields a more compact dimeric form in MsUreG.
PMID- 25846151
TI - Two cases of transplant renal artery thrombosis and spontaneous rupture caused by
mucormycosis.
AB - Mucormycosis is an uncommon infectious complication after renal transplantation
and is associated with fatal outcomes. We report 2 cases of transplant renal
artery thrombosis and spontaneous rupture caused by mucormycosis. As stenosis,
thrombosis, and spontaneous rupture of the transplant renal artery began to occur
in both cases after renal transplantation, nephrectomy of the transplanted kidney
was performed. Postoperative pathological findings in the transplanted kidney
revealed an invasive mucormycosis infection in the renal artery. One patient
survived, but the other patient died. This report also presents the diagnosis and
treatment processes used for this transplant complication.
PMID- 25846144
TI - Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection
and compensated cirrhosis: An integrated safety and efficacy analysis.
AB - Patients with hepatitis C virus (HCV) infection and cirrhosis are
underrepresented in clinical trials of interferon-free regimens of direct-acting
antiviral agents, making it difficult to optimize therapy. We performed a post
hoc analysis of data from seven clinical trials to evaluate the efficacy and
safety of the fixed-dose combination of ledipasvir (LDV) and sofosbuvir (SOF),
with and without ribavirin (RBV), in 513 treatment-naive and previously treated
patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV
SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained
virological response (SVR) 12 weeks after treatment (SVR12) overall and for
subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had
failed previous treatment with a protease-inhibitor regimen. Overall, 493
patients (96%; 95% confidence interval [CI]: 94%-98%) achieved SVR12, 98% of
treatment-naive and 95% of previously treated patients. SVR12 rates did not vary
greatly by treatment duration (95% of patients receiving 12 weeks and 98% of
patients receiving 24 weeks of treatment), nor by addition of RBV (95% of
patients receiving LDV-SOF alone and 97% of those who received LDV-SOF plus RBV),
although previously treated patients receiving 12 weeks of LDV-SOF without RBV
had an SVR12 rate of 90%. One patient discontinued LDV-SOF because of an adverse
event (AE). The most common AEs were headache (23%), fatigue (16%-19%), and
asthenia (14%-16%). One patient (<1%) of those receiving LDV-SOF alone, and 4
(2%) of those receiving LDV-SOF plus RBV had treatment-related serious AEs.
CONCLUSIONS: This analysis suggests that 12 weeks of LDV-SOF is safe and
effective for treatment-naive patients with HCV genotype 1 and compensated
cirrhosis. The relatively lower SVR in treatment-experienced patients treated
with 12 weeks of LDV-SOF raises the question of whether these patients would
benefit from adding RBV or extending treatment duration to 24 weeks.
PMID- 25846152
TI - Advanced waveforms and frequency with spinal cord stimulation: burst and high
frequency energy delivery.
AB - In recent years, software development has been key to the next generation of
neuromodulation devices. In this review, we will describe the new strategies for
electrical waveform delivery for spinal cord stimulation. A systematic literature
review was performed using bibliographic databases, limited to the English
language and human data, between 2010 and 2014. The literature search yielded
three articles on burst stimulation and four articles on high-frequency
stimulation. High-frequency and burst stimulation may offer advantages over tonic
stimulation, as data suggest improved patient tolerance, comparable increase in
function and possible success with a subset of patients refractory to tonic
spinal cord stimulation. High-frequency and burst stimulation are new ways to
deliver energy to the spinal cord that may offer advantages over tonic
stimulation. These may offer new salvage strategies to mitigate spinal cord
stimulation failure and improve cost-effectiveness by reducing explant rate.
PMID- 25846154
TI - Introduction: Putting law to work to improve public health: a national convening.
PMID- 25846155
TI - Community experiments in public health law and policy.
PMID- 25846153
TI - Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation.
AB - Hairy and enhancer of split 1 (Hes1), a basic helix-loop-helix transcriptional
repressor protein, regulates the maintenance of neural stem/progenitor cells by
repressing proneural gene expression via Notch signaling. Previous studies showed
that Hes1 expression oscillates in both mouse embryonic stem cells and neural
stem cells, and that the oscillation contributes to their potency and
differentiation fates. This oscillatory expression depends on the stability of
Hes1, which is rapidly degraded by the ubiquitin/proteasome pathway. However, the
detailed molecular mechanisms governing Hes1 stability remain unknown. We
analyzed Hes1-interacting deubiquitinases purified from mouse embryonic stem
cells using an Hes1-specific antibody, and identified the ubiquitin-specific
protease 27x (Usp27x) as a new regulator of Hes1. We found that Hes1 was
deubiquitinated and stabilized by Usp27x and its homologs ubiquitin-specific
protease 22 (Usp22) and ubiquitin-specific protease 51 (Usp51). Knockdown of
Usp22 shortened the half-life of Hes1, delayed its oscillation, and enhanced
neuronal differentiation in mouse developing brain, whereas mis-expression of
Usp27x reduced neuronal differentiation. These results suggest that these
deubiquitinases modulate Hes1 protein dynamics by removing ubiquitin molecules,
and thereby regulate neuronal differentiation of stem cells.
PMID- 25846156
TI - Domestic legal preparedness and response to Ebola.
PMID- 25846157
TI - Lessons learned from the expansion of naloxone access in Massachusetts and North
Carolina.
PMID- 25846158
TI - E-cigarettes: policy options and legal issues amidst uncertainty.
PMID- 25846159
TI - Creating legal data for public health monitoring and evaluation: delphi standards
for policy surveillance.
PMID- 25846160
TI - Lessons from the residual newborn screening dried blood sample litigation.
PMID- 25846161
TI - Shared use and safe routes to school: managing the fear of liability.
PMID- 25846162
TI - Defining commercial speech in the context of food marketing.
PMID- 25846163
TI - Navigating the incoherence of big data reform proposals.
PMID- 25846165
TI - The Health in All Policies (HiAP) approach and the law: preliminary lessons from
California and Chicago.
PMID- 25846164
TI - The role of law in supporting secondary uses of electronic health information.
PMID- 25846166
TI - Hospitals, collaboration, and community health improvement.
PMID- 25846167
TI - Tribal water rights: exploring dam construction in Indian country.
PMID- 25846168
TI - State health department employees, policy advocacy, and political campaigns:
protections and limits under the law.
PMID- 25846169
TI - Harnessing the public health power of model codes to increase drinking water
access in schools and childcare.
PMID- 25846170
TI - Adventures in nannydom: reclaiming collective action for the public's health.
PMID- 25846171
TI - Mental health emergency detentions and access to firearms.
PMID- 25846172
TI - Human health impacts of climate change: implications for the practice and law of
public health.
PMID- 25846173
TI - Is sharing de-identified data legal? The state of public health confidentiality
laws and their interplay with statistical disclosure limitation techniques.
PMID- 25846174
TI - The four stages of youth sports TBI Policymaking: engagement, enactment,
research, and reform.
PMID- 25846175
TI - Emergency preparedness and response for disabled individuals: implications of
recent litigation.
PMID- 25846176
TI - Bridging the gap between science and law: the example of tobacco regulatory
science.
PMID- 25846177
TI - From beginning to end: the importance of evidence-based policymaking in
vaccination mandates.
PMID- 25846178
TI - Legal challenges to the international deployment of government public health and
medical personnel during public health emergencies: impact on national and global
health security.
PMID- 25846179
TI - Preterm birth and social inequality: assessing the effects of material and
psychosocial disadvantage in a UK birth cohort.
AB - OBJECTIVE: To examine the association between social inequalities and preterm
birth, testing both psychosocial and material determinants. DESIGN: Retrospective
cohort study with linked hospital data. SETTING AND POPULATION: 17 285 women in
England, Scotland, Northern Ireland and Wales giving birth to singletons included
in wave 1 of the UK Millennium Cohort Study. METHODS: Social inequalities were
measured with material (household income, housing tenure) and psychosocial
(education, occupational class, employment, social support) indicators. Analysis
using multivariable logistic regression assessed odds of preterm birth, adjusting
for demographics, health and health-related behaviors, pregnancy and delivery
conditions, and pregnancy complications. MAIN OUTCOME MEASURE: Preterm birth
between 24 and 36 weeks, 6 days' gestation. RESULTS: Initial bivariable analysis
suggested associations between preterm birth and household income, housing
tenure, and education. These effects were largely explained by adjustment for
other social determinants in multivariable models. Following full adjustment,
effects of unemployment [OR = 1.52, 95% confidence interval (CI) 1.21-1.90, p <
0.001] and one indicator of poor social support (OR = 1.17, 95% CI 1.01-1.35, p =
0.04) remained significant. CONCLUSION: Unemployment and lack of social support
are associated with higher risk of preterm birth, supporting the hypothesis that
poor psychosocial circumstances elevate a woman's risk of this adverse perinatal
outcome. Further research is needed to examine the causal pathways through which
social inequalities affect preterm birth.
PMID- 25846180
TI - Environmental sustainability of bioethanol produced from sweet sorghum stem on
saline-alkali land.
AB - Life cycle assessment was conducted to evaluate the energy efficiency and
environmental impacts of a bioethanol production system that uses sweet sorghum
stem on saline-alkali land as feedstock. The system comprises a plant cultivation
unit, a feedstock transport unit, and a bioethanol conversion unit, with 1000L of
bioethanol as a functional unit. The net energy ratio is 3.84, and the net energy
gain is 17.21MJ/L. Agrochemical production consumes 76.58% of the life cycle
fossil energy. The category with the most significant impact on the environment
is eutrophication, followed by acidification, fresh water aquatic ecotoxicity,
human toxicity, and global warming. Allocation method, waste recycling approach,
and soil salinity significantly influence the results. Using vinasse to produce
pellet fuel for steam generation significantly improves energy efficiency and
decreases negative environmental impacts. Promoting reasonable management
practices to alleviate saline stress and increasing agrochemical utilization
efficiency can further improve environmental sustainability.
PMID- 25846181
TI - Effects of feedstock ratio and organic loading rate on the anaerobic mesophilic
co-digestion of rice straw and pig manure.
AB - In order to investigate the effects of feedstock ratio and organic loading rate
(OLR) on the anaerobic mesophilic co-digestion of rice straw (RS) and pig manure
(PM), batch bottle tests (2.5L) were carried out at volatile solid (VS) ratios of
0:1, 1:2, 1:1, 2:1, and 1:0 (RS/PM), and continuous bench experiments (40L) were
carried out at OLRs of 3.0, 3.6, 4.2, 4.8, 6.0, 8.0, and 12.0kg VS/(m(3)d) with
optimal VS ratio. The results showed that the optimal ratio was 1:1 in terms of
biogas yield. Stable biogas production with an average specific biogas production
of 413L/kg VS was obtained at an OLR of 3-8kg VS/(m(3)d). Anaerobic co-digestion
was severely inhibited by the accumulation of volatile fatty acids when the OLR
was 12kg VS/(m(3)d). Further, light and serious foaming were observed at OLR of 8
and 12kg VS/(m(3)d), respectively.
PMID- 25846182
TI - High rate psychrophilic anaerobic digestion of undiluted dairy cow feces.
AB - Novel high rate psychrophilic (20 degrees C) anaerobic digestion (PAD) of
undiluted cow feces (11.5-13.5% total solids) was demonstrated using sequence
batch reactor in long-term operation with successive cycles of 21days treatment
cycle length (TCL). At organic loading rates (OLR) 9.0, 10.0, 11.0 and 12.0g TCOD
kg(-1) inoculum d(-1) average specific methane yield (SMY) was 154.0+/-11.7,
152.1+/-12.2, 126.0+/-2.8 and 116.0+/-6.1NL CH4 per kg of VS fed, respectively.
Volatile solids removal averaged around 31.7+/-3.3%, 32.2+/-1.0%, 27.9+/-2.2% and
23.4+/-0.5%, respectively. Substrate-to-inoculum ratio (SIR; wet-mass basis)
ranged between 1.17+/-0.06 and 1.43+/-0.05. Concentration of volatile fatty acids
in the bioreactors during the TCL indicated that hydrolysis was the rate limiting
reaction. High rate PAD of undiluted cow feces is possible at OLR (g TCOD kg(-1)
inoculum d(-1)) 9.0 and 10.0 with a TCL of 21days; however, OLR of 11.0 and 12.0
are also possible but require longer TCL to maintain the SMY.
PMID- 25846183
TI - Effect of steam explosion on waste copier paper alone and in a mixed
lignocellulosic substrate on saccharification and fermentation.
AB - This study evaluated steam (SE) explosion on the saccharification and
simultaneous saccharification and fermentation (SSF) of waste copier paper. SE
resulted in a colouration, a reduction in fibre thickness and increased water
absorption. Changes in chemical composition were evident at severities greater
than 4.24 resulting in a loss of xylose and the production of breakdown products
known to inhibit fermentation (particularly formic acid and acetic acid). SE did
not improve final yields of glucose or ethanol, and at severities 4.53 and 4.83
reduced yields probably due to the effect of breakdown products and fermentation
inhibitors. However, at moderate severities of 3.6 and 3.9 there was an increase
in initial rates of hydrolysis which may provide a basis for reducing processing
times. Co-steam explosion of waste copier paper and wheat straw attenuated the
production of breakdown products, and may also provide a basis for improving SSF
of lignocellulose.
PMID- 25846184
TI - Continuous background light significantly increases flashing-light enhancement of
photosynthesis and growth of microalgae.
AB - Under specific conditions, flashing light enhances the photosynthesis rate in
comparison to continuous illumination. Here we show that a combination of
flashing light and continuous background light with the same integrated photon
dose as continuous or flashing light alone can be used to significantly enhance
photosynthesis and increase microalgae growth. To test this hypothesis, the green
microalga Dunaliella salina was exposed to three different light regimes:
continuous light, flashing light, and concomitant application of both. Algal
growth was compared under three different integrated light quantities; low,
intermediate, and moderately high. Under the combined light regime, there was a
substantial increase in all algal growth parameters, with an enhanced
photosynthesis rate, within 3days. Our strategy demonstrates a hitherto
undescribed significant increase in photosynthesis and algal growth rates, which
is beyond the increase by flashing light alone.
PMID- 25846185
TI - A biorefining process: Sequential, combinational lignocellulose pretreatment
procedure for improving biobutanol production from sugarcane bagasse.
AB - Here, for the first time, we designed a sequential, combinatorial lignocellulose
pretreatment procedure (SCLPP) for microbial biofuel fermentation to reduce
generation of microbial growth inhibitors and furthermore increase sugar yields.
We tested this pretreatment process using sugarcane bagasse as substrate and
assessed the effectiveness by analysis of biobutanol production through microbial
clostridium beijerinckii NCIMB 8052 conversion. Our results showed that there
were no inhibitory effects when using the hydrolysates as fermentation substrate.
Under the SSF scheme, we observed the highest concentrations of butanol (6.4g/L)
and total ABE (11.9g/L), resulting in a higher ABE productivity, compared with
the SHF method. These findings suggest that the SCLPP is a feasible method for
improving ABE production, lowering microbial inhibitor generation, and ensuring
success in the subsequent fermentation process. Therefore, our work demonstrated
developing a tractable integrated process that facilitates to increase biofuel
production from agricultural residues rich in lignocellulose is feasible.
PMID- 25846186
TI - Comparative study of alkaline hydrogen peroxide and organosolv pretreatments of
sugarcane bagasse to improve the overall sugar yield.
AB - Green liquor (GL) combined with H2O2 (GL-H2O2) and green liquor (GL) combined
with ethanol (GL-ethanol) were chosen for treating sugarcane bagasse. Results
showed that the glucose yield (calculated from the glucose content as a
percentage of the theoretical glucose available in the substrates)of sugarcane
bagasse from GL-ethanol pretreatment (97.7%) was higher than that from GL-H2O2
pretreatment (41.7%) after 72h hydrolysis with 18 filter paper unit (FPU)/g
cellulose for cellulase, 27,175 cellobiase units (CBU)/g-cellulose for beta
glucosidase. Furthermore, about 94.1% of xylan was converted to xylose after GL
ethanol pretreatment without additional xylanase, while the xylose yield was only
29.2% after GL-H2O2 pretreatment. Scanning electron microscopy showed that GL
ethanol pretreatment could break up the fiber severely. Moreover, GL-ethanol
pretreated substrate was more accessible to cellulase and more hydrophilic than
that of GL-H2O2 pretreated. Therefore, GL-ethanol pretreatment is a promising
method for improving the overall sugar (glucose and xylan) yield of sugarcane
bagasse.
PMID- 25846187
TI - Production of d-lactic acid from hardwood pulp by mechanical milling followed by
simultaneous saccharification and fermentation using metabolically engineered
Lactobacillus plantarum.
AB - This study focused on the process development for the d-lactic acid production
from cellulosic feedstocks using the Lactobacillus plantarum mutant, genetically
modified to produce optically pure d-lactic acid from both glucose and xylose.
The simultaneous saccharification and fermentation (SSF) using delignified
hardwood pulp (5-15% loads) resulted in the lactic acid titers of 55.2-84.6g/L
after 72h and increased productivities of 1.77-2.61g/L/h. To facilitate the
enzymatic saccharification of high-load pulp at a fermentation temperature, short
term (?10min) pulverization of pulp was conducted, leading to a significantly
improved saccharification with the suppressed formation of formic acid by
product. The short-term milling followed by SSF resulted in a lactic acid titer
of 102.3g/L, an optical purity of 99.2%, and a yield of 0.879g/g-sugars without
fed-batch process control. Therefore, the process presented here shows promise
for the production of high-titer d-lactic acid using the L. plantarum mutant.
PMID- 25846188
TI - Improvement on sugar cane bagasse hydrolysis using enzymatic mixture designed
cocktail.
AB - The aim of this work was to study cocktail supplementation for sugar cane bagasse
hydrolysis, where the enzymes were provided from both commercial source and
microorganism cultivation (Trichoderma reesei and genetically modified
Escherichia coli), followed by purification. Experimental simplex lattice mixture
design was performed to optimize the enzymatic proportion. The response was
evaluated through hydrolysis microassays validated here. The optimized enzyme
mixture, comprised of T. reesei fraction (80%), endoglucanase (10%) and beta
glucosidase (10%), converted, theoretically, 72% of cellulose present in
hydrothermally pretreated bagasse, whereas commercial Celluclast 1.5L converts
49.11%+/-0.49. Thus, a rational enzyme mixture designed by using synergism
concept and statistical analysis was capable of improving biomass
saccharification.
PMID- 25846189
TI - The coupling of glycolysis and the Rubisco-based pathway through the non
oxidative pentose phosphate pathway to achieve low carbon dioxide emission
fermentation.
AB - In this study, Rubisco-based engineered Escherichia coli, containing two
heterologous enzymes of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco)
and phosphoribulokinase (PrkA), has been shown to be capable of the in situ
recycling of carbon dioxide (CO2) during glycolysis. Two alternative approaches
have been proposed to further enhance the carbon flow from glycolysis to a
Rubisco-based pathway through the non-oxidative pentose phosphate pathway
(NOPPP). The first is achieved by elevating the expression of transketolase I
(TktA) and the second by blocking the native oxidation-decarboxylation reaction
of E. coli by deleting the zwf gene from the chromosome (designated as JB/pTA and
MZB, respectively). Decreases in the CO2 yield and the CO2 evolution per unit
mole of ethanol production by at least 81% and 40% are observed. It is
demonstrated in this study that the production of one mole of ethanol using E.
coli strain MZB, the upper limit of CO2 emission is 0.052mol.
PMID- 25846190
TI - Multiple reuses of Rhodococcus ruber TH3 free cells to produce acrylamide in a
membrane dispersion microreactor.
AB - In this work, multiple reuses of Rhodococcus ruber TH3 free cells for the
hydration of acrylonitrile to produce acrylamide in a membrane dispersion
microreactor were carried out. Through using a centrifuge, the reactions reached
39.9, 39.5, 38.6 and 38.0wt% of the final acrylamide product concentration
respectively within 35min in a four cycle reuse of free cells. In contrast, using
a stirring tank, free cells could only be used once with the same addition speed
of acrylonitrile with a microreactor. Through observing the dissolution behavior
of acrylonitrile microdroplets in a free cell solution using a coaxial
microfluidic device and microscope, it was found that the acrylonitrile
microdroplets with a diameter of 75MUm were rarely observed within a length of
2cm channel within 10s, which illustrated that the microreactor can intensify the
reaction rate to reduce the inhibition of acrylonitrile and acrylamide.
PMID- 25846191
TI - Measuring patient-centered care: An updated systematic review of how studies
define and report concordance between patients' preferences and medical
treatments.
AB - OBJECTIVE: The purpose was to examine recent advances in measuring value
concordance and to highlight best practices. METHODS: The paper updates a prior
systematic review. A systematic review of the literature from 2008 to 2012
identified articles that reported a relationship between patients' preferences
concerning health outcomes and/or medical treatments, and treatment (intended or
actual). Relevant articles were independently abstracted by two reviewers.
RESULTS: The search identified 3635 unique citations, the full text of 187
articles was examined, and 63 articles covering 61 studies were included, nearly
a third more articles than identified in the original review. There were 72
different value concordance calculations, the majority of which were clearly
reported with significance. More studies assessed knowledge, reported on the
association between value concordance and knowledge, and included a decision aid
compared to those in the original review. CONCLUSION: There is increased
reporting of value concordance in the literature. However, large differences
exist in the way that the measure is defined and calculated. The variability
makes it difficult to draw conclusions about the quality of care across studies.
PRACTICE IMPLICATIONS: Value concordance is a critical component of patient
centered care, and further attention is needed to establish standards for
measurement and reporting.
PMID- 25846192
TI - Out-of-office hours nurse-driven acute telephone counselling service in a large
diabetes outpatient clinic: A mixed methods evaluation.
AB - OBJECTIVE: To map the usage of out-of-office hours acute telephone counselling
(ATC) provided by diabetes specialist nurses (n=18) for diabetes patients to
explore potentials for improvement. METHODS: A mixed methods study involved
mapping of ATC-usage during 6 months and a retrospective audit of frequent users.
RESULTS: Altogether, 3197 calls were registered that were related to 592
individual patients, corresponding to 10% of the population. Proportionally more
users suffered from type 1 diabetes (p<0.001). ATC-users' mean HbA1c was 8.8% (73
mmol/mol) compared to 8.1% (65 mmol/mol) for all patients attending the clinic
(p<0.001). Hyperglycaemia was the most frequent reason for calling. The use of
ATC likely prevented 15 admissions. More than half of the calls came from general
nurses based in the community (n=619) and general nurses and nursing assistants
based in care homes (n=1018). The majority (75%) of patients called less than
five times. However, 8% called 16 times or more accounting for 52% of all calls.
A retrospective audit identified them as physically and/or psychologically
fragile patients. CONCLUSION: Hyperglycaemia was the most frequent reason for
calling, and insulin dose adjustment the most frequent advice given. PRACTICE
IMPLICATIONS: Frequent users identified need additional support.
PMID- 25846193
TI - Let-7a inhibits growth and migration of breast cancer cells by targeting HMGA1.
AB - Let-7 is one of the earliest discovered microRNAs (miRNAs) and has been reported
to regulate self renewal and tumorigenicity of breast cancer cells. Let-7a is a
member of this family and its function has not been fully characterized in breast
cancer. First, total RNAs of breast cancer cells (MDA-MB-231, MCF-7), breast
cancer tissues and corresponding adjacent normal tissues were extracted and used
to detect let-7a expression by qRT-PCR. Secondly, the effects of let-7a on
proliferation, colony formation, migration and invasion of breast cancer cells
were assessed by in vitro cell culture experiments. Finally, western blotting was
performed to demonstrate how let-7a regulated HMGA1 expression. We found that let
7a expression was significantly lower in breast cancer cells and breast cancer
tissues compared to corresponding adjacent normal tissues. Cell proliferation,
colony formation, migration and invasion were decreased after overexpression of
let-7a in breast cancer cells and vice versa. Furthermore, we identified the high
mobility group A1 (HMGA1) as a potential target gene of let-7a. Protein
expression of the target gene was significantly downregulated in let-7a mimic
transfected breast cancer cells and significantly upregulated in let-7a inhibitor
transfected breast cancer cells. Our data suggest that let-7a plays an important
role as a tumor suppressor gene by targeting HMGA1, which may open novel
perspectives for clinical treatments against breast cancer.
PMID- 25846194
TI - Clinical, structural, biochemical and X-ray crystallographic correlates of
pathogenicity for variants in the C-propeptide region of the COL3A1 gene.
AB - Vascular Ehlers-Danlos syndrome (vEDS) is a heritable disorder of connective
tissue caused by pathological variants in the COL3A1 gene, which encodes the
alpha1 chain of type III collagen. Type III collagen is a major component of
skin, arterial walls, and the gastrointestinal tract. Collagen III protein
deficiency manifests as an increased risk of rupture, perforation, and dissection
of these structures. The most disruptive gene variants affect the collagen helix
via glycine substitutions or splice donor site mutations. The C-propeptide region
of COL3A1 includes exons 49-52 and has a crucial role in initiating the C
terminal assembly of procollagen monomers in the early stages of collagen
biosynthesis. Nineteen COL3A1 variants have previously been reported in these
exons, of which four were associated with a severe vEDS phenotype. We identified
two novel C-propeptide missense variants; p.Pro1440Leu, p.Arg1432Leu, and a non
stop mutation, c.4400A > T, p. (*1467Leuext*45). These variants produce variable
phenotypes ranging from obvious acrogeria to classical or hypermobile EDS. A
previously reported variant p.Lys1313Arg is of unknown clinical significance but
likely benign, based on this study. Assigning disease pathogenicity remains
complex, clinical phenotyping and crystal structure evidence being crucial. We
briefly compare reported phenotypes for patients with missense variants in the C
propeptide domain for other human collagen disorders including COL1A1 and COL1A2
(osteogenesis imperfecta).
PMID- 25846196
TI - A preliminary mapping of individual, relational, and social factors that impede
disclosure of childhood sexual abuse.
AB - Uncovering the pathways to disclosures of child sexual abuse (CSA) and the
factors influencing the willingness of victims to talk about the abuse is
paramount to the development of powerful practice and policy initiatives. Framed
as a long interview method utilizing a grounded theory approach to analyze data,
the objective of the current study was to provide a preliminary mapping of the
barriers to CSA disclosures through an ecological systemic lens, from a sample of
67 male and female CSA adult survivors, all of whom had recently received
counselling services. The current project led to the identification of three
broad categories of barriers that were each comprised of several subthemes,
namely: Barriers from Within (internalized victim-blaming, mechanisms to protect
oneself, and immature development at time of abuse); Barriers in Relation to
Others (violence and dysfunction in the family, power dynamics, awareness of the
impact of telling, and fragile social network); and Barriers in Relation to the
Social World (labelling, taboo of sexuality, lack of services available, and
culture or time period). This study points to the importance of using a broad
ecological framework to understand the factors that inhibit disclosure of CSA, as
barriers to disclosure do not constrain solely the victims. Results are discussed
in light of their implications for research, prevention and intervention
programs, and social policies and media campaigns, as the burden is on the larger
community to create a climate of safety and transparency that makes the telling
of CSA possible.
PMID- 25846195
TI - Life course pathways of adverse childhood experiences toward adult psychological
well-being: A stress process analysis.
AB - Growing evidence suggests that toxic stressors early in life not only convey
developmental impacts but also augment risk of proliferating chains of additional
stressors that can overwhelm individual coping and undermine recovery and health.
Examining trauma within a life course stress process perspective, we posit that
early childhood adversity carries a unique capacity to impair adult psychological
well-being both independent of and cumulative with other contributors, including
social disadvantage and stressful adult experiences. This study uses data from a
representative population-based health survey (N=13,593) to provide one of the
first multivariate assessments of unique, cumulative, and moderated effects of
adverse childhood experiences (ACEs) toward explaining 3 related yet distinct
measures of adult mental health: perceived well-being, psychological distress,
and impaired daily activities. Results demonstrate support for each set of
hypothesized associations, including exacerbation and amelioration of ACEs
effects by adult stress and resilience resources, respectively. Implications for
services and future research are discussed.
PMID- 25846198
TI - Studying abroad: Exploring factors influencing nursing students' decisions to
apply for clinical placements in international settings.
AB - BACKGROUND: For over 15 years the College of Nursing at the University of
Saskatchewan has facilitated study abroad clinical placements in a number of
countries to enhance student learning. Nursing students often find their study
abroad experience to be a defining moment in their educational program, and in
their personal and professional growth. OBJECTIVES: The main objective of this
research was to explore factors influencing nursing students' decisions to study
abroad. DESIGN: A descriptive longitudinal design study was conducted using an
online survey. SETTINGS: The Study Abroad Survey was distributed to all
undergraduate and graduate nursing students, in all years of all programs, at all
sites of the College of Nursing, University of Saskatchewan in Saskatchewan,
Canada. PARTICIPANTS: A total of 1058 nursing students registered in the 2013
2014 academic year were surveyed. METHODS: The data were collected using an
online survey administered by Campus LabsTM (2014). RESULTS: Students indicated
that their interest in study abroad international experiences was high (84%),
with many perceived benefits, but barriers to participation were also high for
these students. Financial barriers topped the list (71%), followed by family
responsibilities (30%) and job obligations (23%). CONCLUSION: The research
highlights the factors behind student decision making related to international
placements, and provides the basis for improvements to the College of Nursing's
International Study Abroad Program (ISAP). Previous travel and international
service learning, resulting in increased perceived value of a study abroad
experience may prove to be the more significant factor influencing decision
making, rather than financial barrier.
PMID- 25846197
TI - Nurse teacher models in clinical education from the perspective of student nurses
-A mixed method study.
AB - OBJECTIVES: The aim was to describe and compare the clinical teacher's role in
different models of clinical practice from the perspective of student nurses.
DESIGN AND SETTINGS: The study took place in collaboration with two Swedish
universities that applied different educational models in clinical practice. A
mixed method approach was used. The quantitative part had a comparative design
and the qualitative part had a descriptive design. PARTICIPANTS: The study group
consisted of 114 student nurses (response rate 87%). Fifty-three of them had met
clinical teachers employed at the university and not participating in the daily
clinical work (University Nurse Teachers, UNTs), whilst 61 had met clinical
teachers dividing their time between teaching and nursing (Clinical Nurse
Teachers, CNTs). Eight students participated in the qualitative part of the
study. METHODS: A questionnaire including the CLES+T scale was used to ascertain
the students' perception of the clinical teacher's role, complemented by
interviews directed towards an enrichment of this perception. RESULTS: Students
meeting CNTs agreed more strongly than those meeting UNTs that the teacher had
the ability to help them integrate theory and practice. Whilst spontaneous
meetings between students and CNTs occurred, students mostly met UNTs in
seminars. Students meeting UNTs felt alone but did appreciate having someone
outside the clinical environment to provide support if they did not get along
with their preceptor. CONCLUSIONS: In the case of UNTs, it is important that they
keep their knowledge of clinical issues updated and visit the clinical placement
not only for seminars but also to give students emotional support. In the case of
CNTs, it is important that they are members of the faculty at the university,
take part in the planning of the clinical courses and are able to explain the
learning goals to the students.
PMID- 25846200
TI - Antimicrobial and disinfectant resistance of Escherichia coli isolated from giant
pandas.
AB - AIMS: The study aims to demonstrate the antimicrobial and disinfectant resistance
phenotypes and genotypes of Escherichia coli isolates obtained from giant pandas
(Ailuropoda melanoleuca). METHODS AND RESULTS: Antimicrobial testing was
performed according to the standard disk diffusion method. The minimal inhibitory
concentrations (MICs) of disinfectants were determined using the agar dilution
method. All isolates were screened for the presence of antimicrobial and
disinfectant resistance genes and further analysed for genetic relatedness by
pulse-field gel electrophoresis (PFGE). Results showed that 46.6% of the isolates
were resistant to at least one antimicrobial. Escherichia coli isolates showed
resistance to fewer antimicrobials as panda age increased. Among antimicrobial
resistant E. coli isolates, the antimicrobial resistance genes blaCTX-M (88.2%)
and sul1 (92.3%) were most prevalent. The disinfectant resistance genes emrE,
ydgE/ydgF, mdfA and sugE(c) were commonly present (68.2-98.9%), whereas qac and
sugE(p) were relatively less prevalent (0-21.3%). The frequencies of resistance
genes tended to be higher in E. coli isolated in December than in July, and PFGE
profiles were also more diverse in isolates in December. The qacEDelta1 and
sugE(p) genes were higher in adolescent pandas than in any other age groups. PFGE
revealed that antimicrobial resistance correlated well with sampling time and
habitat. CONCLUSIONS: This study demonstrated that antimicrobial and disinfectant
resistance was common in giant panda-derived E. coli, and the antimicrobial
resistance was associated with sampling time and habitat. Escherichia coli could
serve as a critical vector in spreading disinfectant and antimicrobial
resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study that
demonstrated the phenotypic and genetic characterizations of antimicrobial and
disinfectant resistance in E. coli isolates from more than 60 giant pandas.
Frequent transfer of pandas to other cages may lead to the dissemination of
antimicrobial resistance. The study highlights the need for regularly monitoring
the antimicrobial and disinfectant resistance in bacteria from giant pandas.
PMID- 25846201
TI - Improving cold storage and processing traits in potato through targeted gene
knockout.
AB - Cold storage of potato tubers is commonly used to reduce sprouting and extend
postharvest shelf life. However, cold temperature stimulates the accumulation of
reducing sugars in potato tubers. Upon high-temperature processing, these
reducing sugars react with free amino acids, resulting in brown, bitter-tasting
products and elevated levels of acrylamide--a potential carcinogen. To minimize
the accumulation of reducing sugars, RNA interference (RNAi) technology was used
to silence the vacuolar invertase gene (VInv), which encodes a protein that
breaks down sucrose to glucose and fructose. Because RNAi often results in
incomplete gene silencing and requires the plant to be transgenic, here we used
transcription activator-like effector nucleases (TALENs) to knockout VInv within
the commercial potato variety, Ranger Russet. We isolated 18 plants containing
mutations in at least one VInv allele, and five of these plants had mutations in
all VInv alleles. Tubers from full VInv-knockout plants had undetectable levels
of reducing sugars, and processed chips contained reduced levels of acrylamide
and were lightly coloured. Furthermore, seven of the 18 modified plant lines
appeared to contain no TALEN DNA insertions in the potato genome. These results
provide a framework for using TALENs to quickly improve traits in commercially
relevant autotetraploid potato lines.
PMID- 25846202
TI - Authors' reply: Meat subtypes and their association with colorectal cancer:
Systematic review and meta-analysis.
PMID- 25846203
TI - Constraints to nitrogen acquisition of terrestrial plants under elevated CO2.
AB - A key part of the uncertainty in terrestrial feedbacks on climate change is
related to how and to what extent nitrogen (N) availability constrains the
stimulation of terrestrial productivity by elevated CO2 (eCO2 ), and whether or
not this constraint will become stronger over time. We explored the ecosystem
scale relationship between responses of plant productivity and N acquisition to
eCO2 in free-air CO2 enrichment (FACE) experiments in grassland, cropland and
forest ecosystems and found that: (i) in all three ecosystem types, this
relationship was positive, linear and strong (r(2) = 0.68), but exhibited a
negative intercept such that plant N acquisition was decreased by 10% when eCO2
caused neutral or modest changes in productivity. As the ecosystems were markedly
N limited, plants with minimal productivity responses to eCO2 likely acquired
less N than ambient CO2 -grown counterparts because access was decreased, and not
because demand was lower. (ii) Plant N concentration was lower under eCO2 , and
this decrease was independent of the presence or magnitude of eCO2 -induced
productivity enhancement, refuting the long-held hypothesis that this effect
results from growth dilution. (iii) Effects of eCO2 on productivity and N
acquisition did not diminish over time, while the typical eCO2 -induced decrease
in plant N concentration did. Our results suggest that, at the decennial
timescale covered by FACE studies, N limitation of eCO2 -induced terrestrial
productivity enhancement is associated with negative effects of eCO2 on plant N
acquisition rather than with growth dilution of plant N or processes leading to
progressive N limitation.
PMID- 25846204
TI - Acceleratory match-play demands of a Super Rugby team over a competitive season.
AB - The match-play demands of rugby union have increased over time, and these demands
should be quantified so as to provide a basis for optimal player loading during
training. The primary aim of this article was to quantify accelerations,
decelerations, impacts and aggregated body demands during the first half of match
play in a Super Rugby team. The secondary aim was to determine whether these
characteristics are position-specific. Thirty-three players were monitored for 14
matches using global positioning system units with inbuilt microtechnology.
Players were grouped according to positional roles and data were analysed for
those who completed the entire duration of the first half of a given match.
Forwards sustained more (d = 0.44) high-intensity impacts and greater (d = 0.26)
aggregated body demands, while backs had more moderate (d = 0.55) and heavy
accelerations (d = 0.76), and moderate (d = 0.23) and heavy decelerations (d =
0.54). These differences suggest that conditioning and recovery strategies should
reflect the physical demands placed on players in different playing positions.
Forwards should be conditioned with a focus on impacts and require longer
recovery for the same duration of playing time, whereas conditioning for backs
should emphasise rapid accelerations and decelerations.
PMID- 25846205
TI - Toll-like receptors: Activation, signalling and transcriptional modulation.
AB - Families of innate immune receptors serve as the bodies primary defence system by
recognising and rapidly responding to infection by microorganisms or to
endogenous danger signals and initiating inflammatory processes. Whilst Toll-like
receptors (TLRs) were the first family to be discovered, important and exciting
discoveries continue to emerge into the molecular mechanisms that control their
activation and regulation. Herein, I will provide an overview of TLR activation
and their downstream signalling cascades, and discuss some of the recent findings
concerning the assembly of a TLR oligomeric signalling platform, known as the
Myddosome. Further, a brief examination of the importance of crosstalk between
multiple TLRs or between TLRs and other innate immune receptors for appropriate
and coordinated immune responses will be presented. Finally, I will discuss the
importance of mechanisms that regulate TLRs with a focus on the role of
activating transcription factor 3 (ATF3) in modulating transcriptional responses
downstream of TLRs.
PMID- 25846206
TI - Spreading the word: A process evaluation of a voluntary AOD prevention program.
AB - BACKGROUND AND OBJECTIVES: Research on voluntary after-school alcohol and other
drug (AOD) prevention programs is limited. It is important to increase
understanding of students' motivation to attend these types of programs and their
tendency to transfer program information to peers. This paper summarizes efforts
to evaluate process information for CHOICE, a voluntary after-school AOD
prevention program for middle-school youth. METHODS: A survey administered to
1899 students aged 10-16 in seven schools assessed: (1) why students choose to
attend CHOICE (2) barriers to attendance; and (3) how program information is
disseminated to non-participants. Frequencies of responses from participants and
non-participants were compared. RESULTS: Participants were motivated by several
features, most notably, the demeanor of the group leaders and enjoyable
curriculum content. Barriers to attendance were primarily logistic, but results
also suggest that the promotion message should more effectively emphasize that
CHOICE is appropriate for everyone. The majority of students knew about CHOICE,
both through advertising and conversations with friends. Non-participants'
detailed reports of what they heard from friends corresponded closely with what
participants reported sharing. DISCUSSION AND CONCLUSIONS: The use of dynamic
group leaders is critical to engaging students in voluntary programs. Offering
the program on different days of the week or at different times (e.g., before
school) may improve attendance rates. Peer networks represent a critical pathway
for prevention information that can help increase program impact. SCIENTIFIC
SIGNIFICANCE: These results can be used to inform modifications to existing
voluntary after-school AOD prevention programs to obtain higher attendance rates
and more widespread dissemination of the intervention message.
PMID- 25846207
TI - Age-related expression analysis of mouse liver nuclear protein binding to 3'
untranslated region of Period2 gene.
AB - In mammals, both circadian rhythm and aging play important roles in regulating
time-dependent homeostasis. We previously discovered an age-related increase
element binding protein, hnRNP A3, which binds to the 3'-untranslated region
(UTR) of blood coagulation factor IX (FIX). Here, we describe other members of
this protein family, hnRNP C and hnRNP H, which bind to the 3'-UTR of the mouse
circadian clock gene Period 2 (mPer2). RNA electrophoretic mobility shift assays
using a (32)P-labeled Per2 RNA probe coupled with two-dimensional gel
electrophoresis followed by MALDI-TOF/MS peptide mass fingerprint analysis was
used to analyze these proteins. Western blotting suggested that the total
expression of these proteins in mouse liver cell nuclei does not increase with
age. Two-dimensional gel electrophoresis analysis of age-related protein
expression showed that many isoforms of these proteins exist in the liver and
that each protein exhibits a complex age-related expression pattern. These
results suggest that many isoforms of proteins are regulated by different aging
systems and that many age regulation systems function in the liver.
PMID- 25846208
TI - Positive selection drives the evolution of a major histocompatibility complex
gene in an endangered Mexican salamander species complex.
AB - Immune gene evolution can be critical to species survival in the face of
infectious disease. In particular, polymorphism in the genes of the major
histocompatibility complex (MHC) helps vertebrates combat novel and diverse
pathogens by increasing the number of pathogen-derived proteins that can initiate
the host's acquired immune response. In this study, we used a combination of
presumably adaptive and neutral markers to investigate MHC evolution in
populations of five salamander species within the Ambystoma velasci complex, a
group consisting of 15 recently diverged species, several of which are
endangered. We isolated 31 unique MHC class II beta alleles from 75 total
individuals from five species in this complex. MHC heterozygosity was
significantly lower than expected for all five species, and we found no clear
relationship between number of MHC alleles and species range, life history, or
level of heterozygosity. We inferred a phylogeny representing the evolutionary
history of Ambystoma MHC, with which we found signatures of positive selection on
the overall gene, putative peptide-binding residues, and allelic lineages. We
identified several instances of trans-species polymorphism, a hallmark of
balancing selection observed in other groups of closely related species. In
contrast, we did not detect comparable allelic diversity or signatures of
selection on neutral loci. Additionally, we identified 17 supertypes among the 44
unique Ambystoma alleles, indicating that these sequences may encode functionally
distinct MHC variants. We therefore have strong evidence that positive selection
is a major evolutionary force driving patterns of MHC polymorphism in this
recently radiated species complex.
PMID- 25846209
TI - Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in
birch pollen-allergic patients.
AB - BACKGROUND: Sublingual immunotherapy (SLIT) applied to type I respiratory
allergies is commonly performed with natural allergen extracts. Herein, we
developed a sublingual tablet made of pharmaceutical-grade recombinant Bet v
1.0101 (rBet v 1) and investigated its clinical safety and efficacy in birch
pollen (BP)-allergic patients. METHODS: Following expression in Escherichia coli
and purification, rBet v 1 was characterized using chromatography, capillary
electrophoresis, circular dichroism, mass spectrometry and crystallography.
Safety and efficacy of rBet v 1 formulated as a sublingual tablet were assessed
in a multicentre, double-blind, placebo-controlled study conducted in 483
patients with BP-induced rhinoconjunctivitis. RESULTS: In-depth characterization
confirmed the intact product structure and high purity of GMP-grade rBet v 1. The
crystal structure resolved at 1.2 A documented the natural conformation of the
molecule. Native or oxidized forms of rBet v 1 did not induce the production of
any proinflammatory cytokine by blood dendritic cells or mononuclear cells. Bet v
1 tablets were well tolerated by patients, consistent with the known safety
profile of SLIT. The average adjusted symptom scores were significantly decreased
relative to placebo in patients receiving once daily for 5 months rBet v 1
tablets, with a mean difference of 17.0-17.7% relative to the group treated with
placebo (P < 0.025), without any influence of the dose in the range (12.5-50 MUg)
tested. CONCLUSION: Recombinant Bet v 1 has been produced as a well-characterized
pharmaceutical-grade biological drug. Sublingual administration of rBet v 1
tablets is safe and efficacious in patients with BP allergic rhinoconjunctivitis.
PMID- 25846210
TI - Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate
conserved interactions with membranes.
AB - Class 1 cytokine receptors regulate essential biological processes through
complex intracellular signalling networks. However, the structural platform for
understanding their functions is currently incomplete as structure-function
studies of the intracellular domains (ICDs) are critically lacking. The present
study provides the first comprehensive structural characterization of any
cytokine receptor ICD and demonstrates that the human prolactin (PRL) receptor
(PRLR) and growth hormone receptor (GHR) ICDs are intrinsically disordered
throughout their entire lengths. We show that they interact specifically with
hallmark lipids of the inner plasma membrane leaflet through conserved motifs
resembling immuno receptor tyrosine-based activation motifs (ITAMs). However,
contrary to the observations made for ITAMs, lipid association of the PRLR and
GHR ICDs was shown to be unaccompanied by changes in transient secondary
structure and independent of tyrosine phosphorylation. The results of the present
study provide a new structural platform for studying class 1 cytokine receptors
and may implicate the membrane as an active component regulating intracellular
signalling.
PMID- 25846211
TI - Nutritional supplementation and artificial reproductive technique (ART) outcomes.
AB - Approximately one in six couples suffer from subfertility, and many seek
treatment with artificial reproductive technologies (ART). Despite improvements
in laboratory techniques and ovarian stimulation, ongoing pregnancy rates per
cycle remain at ~25%. Couples wanting to improve their chances may turn to
adjuvant therapies, such as nutritional supplements. There is growing evidence
that periconceptional nutritional status is a key determinant of fertility and
long-term health of the offspring, and a lucrative market has developed to meet
the demand based on these benefits. However, the practice of routine dietary
supplementation before and during IVF treatment has not been subject to well
powered prospective randomised trials. In this article, the potential roles of
specific nutritional supplements in the context of improving IVF outcomes are
reviewed and an assessment is made of the evidence base supporting their clinical
use in this context. Finally, current research needs in the field are outlined.
PMID- 25846212
TI - Selenoprotein Genes Exhibit Differential Expression Patterns Between Hepatoma
HepG2 and Normal Hepatocytes LO2 Cell Lines.
AB - The purpose of this study was to compare messenger RNA (mRNA) expression of
selenoprotein genes between hepatoma HepG2 and normal hepatocytes LO2 cell lines.
Liver HepG2 and LO2 cells were cultured in 12-well plates under the same
condition until cells grew to complete confluence, and then cells were harvested
for total RNA and protein extraction. The qPCRs were performed to compare gene
expression of 14 selenoprotein genes and 5 cancer signaling-related genes. Enzyme
activities were also assayed. The results showed that human hepatoma HepG2 cells
grew faster than normal hepatocytes LO2 cells. Among the genes investigated, 10
selenoprotein genes (Gpx1, Gpx3, Gpx4, Selx, Sepp, Sepw1, Sepn1, Selt, Seli,
Selh) and 3 cancer signaling-related genes (Bcl-2A, caspase-3, and P38) were
upregulated (P < 0.05), while Selo and Bcl-2B were downregulated (P < 0.05) in
hepatoma HepG2 cells compared to LO2 cells. Significant correlations were found
between selenoprotein genes and the cancer signaling-related genes Caspase3, P53,
Bc1-2A, and Bc1-2B. Our results revealed that selenoprotein genes were aberrantly
expressed in hepatoma HepG2 cells compared to normal liver LO2 cells, which
indicated that those selenoprotein genes may play important roles in the
occurrence and development of liver carcinogenesis.
PMID- 25846213
TI - Effects of Boric Acid on Fracture Healing: An Experimental Study.
AB - Boric acid (BA) has positive effects on bone tissue. In this study, the effects
of BA on fracture healing were evaluated in an animal model. Standard closed
femoral shaft fractures were created in 40 male Sprague-Dawley rats under general
anesthesia. The rats were allocated into five groups (n = 8 each): group 1,
control with no BA; groups 2 and 3, oral BA at doses of 4 and 8 mg/kg/day,
respectively; group 4, local BA (8 mg/kg); and group 5, both oral and local BA (8
mg/kg/day orally and 8 mg/kg locally). After closed fracture creation, the
fracture line was opened with a mini-incision, and BA was locally administered to
the fracture area in groups 4 and 5. In groups 2, 3, and 5, BA was administered
by gastric gavage daily until sacrifice. The rats were evaluated by clinical,
radiological, and histological examinations. The control group (group 1)
significantly differed from the local BA-exposed groups (groups 4 and 5) in the
clinical evaluation. Front-rear and lateral radiographs revealed significant
differences between the local BA-exposed groups and the control and other groups
(p < 0.05). Clinical and radiological evaluations demonstrated adequate agreement
between observers. The average histological scores significantly differed across
groups (p = 0.007) and were significantly higher in groups 4 and 5 which were the
local BA (8 mg/kg) and both oral and local BA (8 mg/kg/day orally and 8 mg/kg
locally), respectively, compared to the controls. This study suggests that BA may
be useful in fracture healing. Further research is required to demonstrate the
most effective local dosage and possible use of BA-coated implants.
PMID- 25846214
TI - Stroke in Bahrain: rising incidence, multiple risk factors, and suboptimal care.
AB - The incidence of stroke in Bahrain is rising in the Bahraini population and has
nearly doubled over the last 16 years, while the incidence in the non-Bahraini
population has not changed. Incidence of stroke in the Bahraini population
(110/100,000) is now much greater than in the non-Bahraini population
(27/100,000). The Bahraini stroke population is 10 years younger than Western
comparators with a much higher prevalence of many of the risk factors for stroke,
including diabetes (54%), hypertension (75%) and hyperlipidemia (34%). The
combination of an ageing Bahraini population alongside a high prevalence of risk
factors suggests a 'ticking time bomb' that is likely to see a continuing rise in
the incidence of stroke. The quality of risk factor prevention and hospital-based
stroke care is therefore crucial in Bahrain. While 88% of patients were scanned
within 24 h and 86% with non-haemorrhagic strokes were commenced on aspirin
within 48 h, none of the patients received thrombolysis or were admitted to a
stroke unit. Improvement of stroke outcomes in Bahrain could be achieved through
implementation of evidence-based measures, including improved risk factor
management in primary care and stroke units and thrombolysis in secondary care.
PMID- 25846215
TI - Increased risk for atypical fractures associated with bisphosphonate use.
AB - BACKGROUND: Studies suggest an increasing occurrence of atypical femoral
fractures with the use of bisphosphonates. OBJECTIVE: To examine whether the use
of bisphosphonates increases the risk for atypical fractures. DESIGN: Systematic
review and meta-analysis. DATA SOURCES: Literature search of MEDLINE, Embase and
Cochrane CENTRAL (1948-June 2013). REVIEW METHODS: SELECTION CRITERIA: (i)
randomized controlled trial or an observational study, (ii) evaluated
bisphosphonate therapy versus no treatment and (iii) reported an incidence of
subtrochanteric or diaphyseal fracture individually, or a composite of both. Two
independent investigators completed study selection, data extraction and validity
assessment. The Cochrane Risk of Bias Tool was used to assess the quality of
included studies. RESULTS: Ten (n = 658497) studies were included in the meta
analysis which demonstrated a statistically significant increased risk of
subtrochanteric or diaphyseal fracture with bisphosphonate use [adjusted odds
ratios (AOR) = 1.99, 95% confidence intervals (CI)= 1.28-3.10] with I (2) = 84.3%
(95% CI = 73.5%-89.5%) and Egger P = 0.01. Subtrochanteric fractures showed an
AOR = 2.71 (95% CI = 1.86-3.95) with I (2) = 83.6% (95% CI = 64.3%-90.3%) and
Egger's P = 2.29. Diaphyseal fractures had an AOR = 2.06 (95% CI = 1.70-2.50), I
(2) = 29.7% (95% CI = 0%-73.7%) and Egger's P = 1.22. CONCLUSION: Results suggest
there is an increased risk for atypical fractures associated with bisphosphonates
and raises awareness to the potential complications related with bisphosphonates.
These findings warrant the comprehensive evaluation of patients before initiating
bisphosphonate therapy and highlights the need for additional medical decision
analyses in future studies to compare the benefit over potential harms of
bisphosphonate therapy.
PMID- 25846216
TI - Mental health symptoms and patient-reported diabetes symptom burden: implications
for medication regimen changes.
AB - AIMS: To examine the relative contribution of glycaemic control (HbA1C) and
depressive symptoms on diabetes-related symptom burden (hypoglycaemia and
hyperglycaemia) in order to guide medication modification. METHODS: Secondary
analysis of medical records data and questionnaires collected from a
racially/ethnically diverse sample of adult patients with type 2 diabetes (n =
710) from seven outpatient clinics affiliated with an academic medical centre
over a 1-year period as part of the Reducing Racial Disparities in Diabetes:
Coached Care (R2D2C2) study. RESULTS: Results from linear regression analysis
revealed that patients with high levels of depressive symptoms had more diabetes
related symptom burden (both hypoglycaemia and hyperglycaemia) than patients with
low levels of depressive symptoms (betas = 0.09-0.17, Ps < 0.02). Furthermore,
results from two logistic regression analyses suggested that the odds of regimen
intensification at 1-year follow-up was marginally associated with patient
reported symptoms of hypoglycaemia [adjusted odds ratio (aOR) = 1.24, 95% CI:
0.98-1.58; P = 0.08] and hyperglycaemia (aOR = 1.21, 95% CI: 1.00-1.46; P =
0.05), after controlling for patients' HbA1C, comorbidity, insulin use and
demographics. These associations, however, were diminished for patients with high
self-reported hypoglycaemia and high levels of depressive symptoms, but not low
depressive symptoms (interaction terms for hypoglycaemia by depressive symptoms,
aOR = 0.98, 95% CI: 0.97-0.99; P = 0.03). CONCLUSIONS: Mental health symptoms are
associated with higher levels of patient-reported of diabetes-related symptoms,
but the association between diabetes-related symptoms and subsequent regimen
modifications is diminished in patients with greater depressive symptoms.
Clinicians should focus attention on identifying and treating patients' mental
health concerns in order to address the role of diabetes-related symptom burden
in guiding physician medication prescribing behaviour.
PMID- 25846218
TI - Osteoarthritis in perspective.
PMID- 25846217
TI - Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite
scaffold augments bone regeneration.
AB - Controlled delivery of biological cues through synthetic scaffolds to enhance the
healing capacity of bone defects is yet to be realized clinically. The purpose of
this study was development of a bioactive tissue-engineered scaffold providing
the sustained delivery of an osteoinductive drug, dexamethasone disodium
phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous
baghdadite (BD; Ca3 ZrSi2 O9 ) scaffolds, a zirconia-modified calcium silicate
ceramic, was coated with DXP-encapsulated CN nanoparticles (DXP-CN) using
nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer
concentrations were optimized to achieve a homogeneous distribution of hydrogel
coating within BD scaffolds. Dynamic laser scattering indicated an average size
of 521 +/- 21 nm for the DXP-CN nanoparticles. In vitro drug-release studies
demonstrated that the developed DXP-CN-GX hydrogel-coated BD scaffolds (DXP-CN-GX
BD) resulted in a sustained delivery of DXP over the 5 days (78 +/- 6% of drug
release) compared with burst release over 1 h, seen from free DXP loaded in
uncoated BD scaffolds (92 +/- 8% release in 1 h). To estimate the influence of
controlled delivery of DXP from the developed scaffolds, the effect on MG 63
cells was evaluated using various bone differentiation assays. Cell culture
within DXP-CN-GX-BD scaffolds demonstrated a significant increase in the
expression of early and late osteogenic markers of alkaline phosphatase activity,
collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The
results suggest that the DXP-releasing nanostructured hydrogel integrated within
the BD scaffold caused sustained release of DXP, improving the potential for
osteogenic differentiation. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 25846219
TI - Developing an evidence-based nursing protocol on wound drain management for total
joint arthroplasty.
AB - BACKGROUND: Although various drains have long been used for many years in total
joint replacement, there is a paucity of evidence for the benefit of drain
applications. Evidence suggests inconsistent practice in the use of drainage
systems, whether intermittently applying suction or free of suction in the
application of drainage systems, as well as the optimal timing for wound drain
removal. AIM: It aimed to perform a systematic review to develop an evidence
based nursing protocol to manage wound drainage following total joint
arthroplasty. METHODS: A comprehensive systematic review of available evidence up
to 2013. Searches of the EMBASE, Cochrane library, CINAHL, Medline electronic
databases and an internet search by Yahoo and Google engine returned 2840
records, of which 11 met the inclusion criteria for this review. A further two
papers were obtained through scanning the reference lists of those articles
included from the initial literature search. RESULTS: Different clamping times
were retrieved from the literature. A protocol was adapted for clinical
application according to the summary of the retrieved information. It is
suggested that clamping is performed 1 h after the insertion of suction drains
post-operatively in the operating theatre. Wound drains should be clamped for 1 h
if blood loss is more than 600 ml in 6 h in first 24 h. Wound drains should be
clamped for 1 h if blood loss is more than 800 ml in 8 h thereafter. It is
suggested that the drainage reservoir bottle should be mark and findings recorded
in line with the principle of drain clamping. This means that the amount of
drainage is measured and recorded every 6 h in first 24 h and every 8 h
thereafter. It is suggested that wound drains should be remove before 48 h after
TJR. If blood loss is less than 50 ml in past 6 h or less than 70 ml in past 8 h,
the drain should be remove and the wound site should be monitored closely.
CONCLUSION: This paper has guided nurses to develop an evidence-based protocol to
improve patient care on wound drain management. Further study is necessary to
evaluate the effectiveness of the protocol.
PMID- 25846220
TI - Orthopaedic nurses' attitudes towards clinical nursing research - A cross
sectional survey.
AB - The call for evidence-based knowledge in clinical nursing practice has increased
during recent decades and research in orthopaedic nursing is needed to improve
patients' conditions, care and treatment. A descriptive cross-sectional survey
was conducted to determine the self-perceived theoretical knowledge and practical
research competencies among orthopaedic nurses and their interest and motivation
to increase these in everyday practice. A newly developed questionnaire was given
to a convenience sample of 87 orthopaedic nurses. Forty three orthopaedic nurses
(49.4%) completed the questionnaire. The results indicated that despite the
majority of orthopaedic nurses having low self-perceived theoretical knowledge
and practical research competencies, their interest and motivation to improve
these were high, especially their inner motivation. However, the nurses' inner
motivation was inhibited by a lack of acceptance from colleagues and section head
nurses and a shortage of time. This study forms a baseline as a part of a larger
study and contributes knowledge useful to other orthopaedic departments with an
interest in optimizing nursing research to improve orthopaedic nursing care
quality.
PMID- 25846221
TI - Developing a programme of patient 'streaming' in an emergency department.
AB - Orthopaedic and musculoskeletal injuries are commonly identified in the emergency
department (ED). Whilst much orthopaedic trauma literature focuses on fractures
of the proximal femur, raising key issues such as length of stay and timely
discharge, the start of the patients' journey is just as important in ensuring an
appropriate assessment and a smooth transition through each stage of care. In the
UK targets have been set for proximal hip fractured patients to attend theatre
within 48 hours of admission, if fit. Appraising such patients expediently on
initial point of contact in the ED has demonstrated that a number of factors can
impinge and delay the patients' progress. This said a large number of other
orthopaedic and musculoskeletal self presenting patients rely on the same
appropriate transition to suitable medical assistance. The emergency department
triage system has been used in the UK in its latest format since 2001, yet
elderly patients with painful Colles fractures find they wait for specialist
attention in a linear queue, possibly over extended lengths of time. This short
paper explores how 'streaming' patients in one local ED has improved
waiting/treatment times, and identified the fact that in some months (December
2012), 1 in 3 attendees present with a musculoskeletal problem. Using audit data
collected over the last four years the benefits of 'streaming' patients is
evident.
PMID- 25846222
TI - Bowel management post major joint arthroplasty: results from a randomised
controlled trial.
AB - AIM: To evaluate the effect of a new post-operative bowel protocol in total hip
and total knee replacement patients. BACKGROUND: Up to 65% of total hip and total
knee replacement patients experience some degree of constipation post
operatively. A lack of robust evidence to guide bowel management and reduce
constipation in this cohort was the impetus for this study. DESIGN: A multisite
cluster randomised trial in private secondary and tertiary hospitals. METHODS: In
total 331 patients were recruited across seven Australian hospitals over 13
months. Control participants (n = 171) received routine bowel management whilst
intervention participants (n = 160) received bowel management as per the trial
protocol. RESULTS: Intervention patients took 6 days less than controls to return
to normal bowel function, and were more than seven times more likely to return to
normal bowel function by day 5 post operatively. Age, gender and length of pre
operative fasting had no effect on these outcomes. CONCLUSION: These results
support the use of the Murdoch Bowel Protocol((r)) for hip and knee replacement
patients and may be relevant for other patient groups who experience opioid
induced bowel dysfunction.
PMID- 25846223
TI - A longitudinal study of quality of life and functional status in total hip and
total knee replacement patients.
AB - BACKGROUND: Primary total hip and primary total knee surgeries are commonly
performed to improve patients' quality of life and functional status. AIM: This
longitudinal retrospective study (N = 851) examined self-reported quality of life
and functional status over the preoperative and postoperative periods: 12 months
prior to surgery, one month prior to surgery and 12 months following surgery.
METHODS: A linear mixed effects model was used to analyze the changes in quality
of life and functional status over the sampling period. RESULTS: Patients in the
convenience sample reported improvements in quality of life and functional status
utilizing the SF-12 and Oxford Hip and Oxford Knee, although differences were
noted by procedure and gender. Total hip patients tended to demonstrate greater
improvement than total knee patients and males reported higher levels of physical
and mental quality of life as well as functional status when compared to females.
Of particular note was that mental health scores were consistently lower in both
total hip and total knee replacement patients across the perioperative period and
up to one year postoperative. CONCLUSION: This study identifies an opportunity
for health care providers to proactively address the mental health of total hip
and total knee replacement patients throughout their joint replacement
trajectory.
PMID- 25846226
TI - Alpha-synuclein modulates NR2B-containing NMDA receptors and decreases their
levels after rotenone exposure.
AB - Alpha-synuclein (alpha-syn) is the main protein component of Lewy bodies (LBs),
that together with nigrostriatal dopamine neuron loss constitute typical
pathological hallmarks of Parkinson's disease (PD). Glutamate N-methyl-d
aspartate receptor (NMDAR) abnormalities, peculiarly involving NR2B-containing
NMDAR, have been observed in the brain of PD patients and in several experimental
models of the disease. Recent findings, indicating that alpha-syn can modulate
NMDAR trafficking and function, suggest that this protein may be a pivotal
regulator of NMDAR activity. Prompted by these evidences, we used fluorescence
immunocytochemistry, western blotting and ratiometric Ca(2+) measurements to
investigate whether wild type (wt) or C-terminally truncated alpha-syn can
specifically modulate NR2B-containing NMDAR levels, subcellular trafficking and
function. In addition, we evaluated whether the exposure of primary cortical
neurons to increasing concentrations of rotenone could differentially regulate
NR2B levels and cell viability in the presence or in the absence of alpha-syn.
Our results indicate that both wt and C-terminally truncated alpha-syn negatively
modulate NR2B-containing NMDAR levels, membrane translocation and function.
Moreover, we found that absence of alpha-syn abolishes the rotenone-dependent
decrease of NR2B levels and reduces neuronal vulnerability in primary cortical
neurons. These findings suggest that alpha-syn can modulate neuronal resilience
by regulating NR2B-containing NMDAR, whose specific alterations could connect
alpha-syn pathology to neuronal degeneration in PD.
PMID- 25846227
TI - Learning Process During Risk Detection in Adolescents With ADHD.
AB - OBJECTIVE: To evaluate and describe the performance during the learning process
of risk-detection versus risk-benefit processing in adolescents diagnosed with
ADHD. METHOD: Thirty-five adolescents with ADHD and 26 paired controls
participated. The tests applied are Iowa-type children version paradigm and
Stroop test. RESULTS: Adolescents with ADHD exhibited lower risk-benefit
processing capacity and lower ability to detect risk selections; main findings
also indicate that adolescents with ADHD were slower to learn to avoid risk
choices. In addition, they also presented a deficient inhibitory control.
CONCLUSION: Results confirm the presence of a deficit in advantageous choice in
adolescents with ADHD. By providing a measure of risk choice-and not only a net
score-we show that adolescents with ADHD also fail to avoid risk choices. This
deficit is mainly because they are slower in learning how to avoid risk choices,
and not simply deficient. Literature is scarce concerning studies with Iowa-type
paradigms in samples intregated exclusively by adolescents. More research is
needed to clarify the nature of these deficiencies.
PMID- 25846228
TI - Association of the Conners' Kiddie Continuous Performance Test (K-CPT)
Performance and Parent-Report Measures of Behavior and Executive Functioning.
AB - OBJECTIVE: To explore the relationship between the Conners' Kiddie Continuous
Performance Test (K-CPT) performance and parent-report measures of child behavior
and executive functioning, and clarify the role of sex in K-CPT performance in
preschoolers. METHOD: Mothers and children recruited to the Health Outcomes and
Measures of the Environment Study with complete 5-year assessment data relevant
to the analyses were included ( N = 127). We examined the association between K
CPT scores and Behavior Assessment System for Children-Second Edition (BASC-2)
and Behavior Rating Inventory of Executive Function (BRIEF) scores, with
covariate adjustment. RESULTS: We found no significant associations between K
CPT, BASC-2, and BRIEF scores in the full sample. In sex-stratified analyses, we
found unusually fast reaction time on K-CPT was related to executive control
difficulties in girls, whereas unusually slow reaction time was related to the
same difficulties in boys. Omission errors were associated with executive
difficulties only in boys. CONCLUSION: The K-CPT may prove to be a useful
indicator for early onset of executive control difficulties in preschool-aged
children.
PMID- 25846229
TI - The Prevalence and Comorbidity Rates of ADHD Among School-Age Children in Turkey.
AB - OBJECTIVE: The aim of the present study was to explore the prevalence and
comorbidity rates of ADHD in a community sample of school-age children. METHOD:
Participants were 1,508 children aged 6 to 14 years. Parents and teachers of each
child completed the Turgay Diagnostic and Statistical Manual of Mental Disorders
(4th ed.; DSM-IV) Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S). Screen
positive cases were interviewed using the Schedule for Affective Disorders and
Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL).
Diagnoses were based on DSM-IV criteria. RESULTS: The prevalence rate of ADHD was
8%. Children from extended families had extremely high rates (46.4%) of ADHD.
Sixty percent of children with ADHD had one or more comorbid diagnoses. The most
common comorbidities were learning disorders (35.7%) and oppositional defiant
disorder (22.6%). CONCLUSION: The prevalence and comorbidity rates of ADHD in
school-age children in Turkey are similar to those found in previous studies in
other countries.
PMID- 25846230
TI - The tolerance of the human body to automobile collision impact - a systematic
review of injury biomechanics research, 1990-2009.
AB - Road traffic injuries account for 1.3 million deaths per year world-wide.
Mitigating both fatalities and injuries requires a detailed understanding of the
tolerance of the human body to external load. To identify research priorities, it
is necessary to periodically compare trends in injury tolerance research to the
characteristics of injuries occurring in the field. This study sought to perform
a systematic review on the last twenty years of experimental injury tolerance
research, and to evaluate those results relative to available epidemiologic data.
Four hundred and eight experimental injury tolerance studies from 1990-2009 were
identified from a reference index of over 68,000 papers. Examined variables
included the body regions, ages, and genders studied; and the experimental models
used. Most (20%) of the publications studied injury to the spine. There has also
been a substantial volume of biomechanical research focused on upper and lower
extremity injury, thoracic injury, and injury to the elderly - although these
injury types still occur with regularity in the field. In contrast, information
on pediatric injury and physiological injury (especially in the central nervous
system) remains lacking. Given their frequency of injury in the field, future
efforts should also include improving our understanding of tolerances and
protection of vulnerable road users (e.g., motorcyclists, pedestrians).
PMID- 25846231
TI - Full Bayesian evaluation of the safety effects of reducing the posted speed limit
in urban residential area.
AB - Full Bayesian (FB) before-after evaluation is a newer approach than the empirical
Bayesian (EB) evaluation in traffic safety research. While a number of earlier
studies have conducted univariate and multivariate FB before-after safety
evaluations and compared the results with the EB method, often contradictory
conclusions have been drawn. To this end, the objectives of the current study
were to (i) perform a before-after safety evaluation using both the univariate
and multivariate FB methods in order to enhance our understanding of these
methodologies, (ii) perform the EB evaluation and compare the results with those
of the FB methods and (iii) apply the FB and EB methods to evaluate the safety
effects of reducing the urban residential posted speed limit (PSL) for policy
recommendation. In addition to three years of crash data for both the before and
after periods, traffic volume, road geometry and other relevant data for both the
treated and reference sites were collected and used. According to the model
goodness-of-fit criteria, the current study found that the multivariate FB model
for crash severities outperformed the univariate FB models. Moreover, in terms of
statistical significance of the safety effects, the EB and FB methods led to
opposite conclusions when the safety effects were relatively small with high
standard deviation. Therefore, caution should be taken in drawing conclusions
from the EB method. Based on the FB method, the PSL reduction was found effective
in reducing crashes of all severities and thus is recommended for improving
safety on urban residential collector roads.
PMID- 25846232
TI - Methodological guidelines for developing accident modification functions.
AB - This paper proposes methodological guidelines for developing accident
modification functions. An accident modification function is a mathematical
function describing systematic variation in the effects of road safety measures.
The paper describes ten guidelines. An example is given of how to use the
guidelines. The importance of exploratory analysis and an iterative approach in
developing accident modification functions is stressed. The example shows that
strict compliance with all the guidelines may be difficult, but represents a
level of stringency that should be strived for. Currently the main limitations in
developing accident modification functions are the small number of good
evaluation studies and the often huge variation in estimates of effect. It is
therefore still not possible to develop accident modification functions for very
many road safety measures.
PMID- 25846233
TI - Using Adobe Flash animations of electron transport chain to teach and learn
biochemistry.
AB - Teaching the subject of the electron transport chain is one of the most
challenging aspects of the chemistry curriculum at the high school level. This
article presents an educational program called "Electron Transport Chain" which
consists of 14 visual animations including a biochemistry quiz. The program was
created in the Adobe Flash CS3 Professional animation program and is designed for
high school chemistry students. Our goal is to develop educational materials that
facilitate the comprehension of this complex subject through dynamic animations
which show the course of the electron transport chain and simultaneously explain
its nature. We record the process of the electron transport chain, including
connections with oxidative phosphorylation, in such a way as to minimize the
occurrence of discrepancies in interpretation. The educational program was
evaluated in high schools through the administration of a questionnaire, which
contained 12 opened-ended items and which required participants to evaluate the
graphics of the animations, chemical content, student preferences, and its
suitability for high school biochemistry teaching.
PMID- 25846234
TI - T-cell chronic lymphocytic leukemia or small-cell variant of T-cell
prolymphocytic leukemia: a historical perspective and search for consensus.
AB - There is a rich history behind the extinct entity 'T-cell chronic lymphocytic
leukemia (T-CLL)' and the now-established replacement, small-cell variant of T
cell prolymphocytic leukemia (T-PLL-sv). Herein, we review the history of the
events, observations, and discussions that led to this replacement. We also
provide a systematic analysis of all previously reported cases of T-PLL-sv as
well as our four new additional cases. Despite the higher frequency of a normal
karyotype and perhaps an overrepresented CD4(-) CD8(-) immunophenotype among
these patients (compared to T-PLL in general) as well as bland morphology (that
makes them superficially appear more similar to B-CLL), we argue that the current
World Health Organization (WHO)-based classification as T-PLL-sv is adequate and
should continue for the time being. Morphologically, T-PLL-sv represents
approximately one-fifth of all T-PLL cases. However, morphology alone does not
determine the clinical course and should not be the basis for clinical decision
making and prognostication. We propose a clonal evolution model in which mature T
cell leukemias classified in the past as T-CLL are perhaps T-PLL diagnosed early
in the course of the disease. Future research using next-generation sequencing,
comparative genomic hybridization, and molecular array studies, including serial
analyses of individual cases over time, is needed to better identify this rarely
diagnosed, inherently controversial form of T-cell leukemia.
PMID- 25846235
TI - A bioelectronic system for insulin release triggered by ketone body mimicking
diabetic ketoacidosis in vitro.
AB - A bioelectronic system composed of two modified electrodes, one activated in the
presence of ketone bodies, a biomarker of diabetic ketoacidosis, and another
releasing insulin upon receiving a signal, was designed and tested in vitro to
operate as a Sense-and-Act device. The functional integration of biomarker
sensing and insulin-releasing electrodes represents a step to a theranostic
system with autonomous operation.
PMID- 25846236
TI - A Non-Invasive NMR Method Based on Histidine Imidazoles to Analyze the pH
Modulation of Protein-Nucleic Acid Interfaces.
AB - A useful (2) J(N-H) coupling-based NMR spectroscopic approach is proposed to
unveil, at the molecular level, the contribution of the imidazole groups of
histidines from RNA/DNA-binding proteins on the modulation of binding to nucleic
acids by pH. Such protonation/deprotonation events have been monitored on the
single His96 located at the second RNA/DNA recognition motif (RRM2) of T-cell
intracellular antigen-1 (TIA-1) protein. The pKa values of the His96 ionizable
groups were substantially higher in the complexes with short U-rich RNA and T
rich DNA oligonucleotides than those of the isolated TIA-1 RRM2. Herein, the
methodology applied to determine changes in pKa of histidine side chains upon
DNA/RNA binding, gives valuable information to understand the pH effect on
multidomain DNA/RNA-binding proteins that shuttle among different cellular
compartments.
PMID- 25846242
TI - Triple-quantum-filtered sodium imaging at 9.4 Tesla.
AB - PURPOSE: Efficient acquisition of triple-quantum-filtered (TQF) sodium images at
ultra-high field (UHF) strength. METHODS: A three-pulse preparation and a stack
of double-spirals were used for the acquisition of TQF images at 9.4 Tesla. The
flip angles of the TQ preparation were smoothly reduced toward the edge of k
space along the partition-encoding direction. In doing so, the specific
absorption rate could be reduced while preserving the maximal signal intensity
for the partitions most relevant for image contrast in the center of k-space.
Simulations, phantom and in vivo measurements were used to demonstrate the
usefulness of the proposed method. RESULTS: A higher sensitivity (~ 20%) was
achieved compared to the standard acquisition without flip angle apodization.
Signals from free sodium ions were successfully suppressed irrespective of the
amount of apodization used. B0 corrected TQF images with a nominal resolution of
5 * 5 * 5 mm(3) and an acceptable signal-to-noise ratio could be acquired in vivo
within 21 min. CONCLUSION: Conventional TQF in combination with flip angle
apodization permits to exploit more efficiently the increased sensitivity
available at 9.4T.
PMID- 25846243
TI - Erratum to: surgical therapy of neuroendocrine neoplasm with hepatic metastasis:
patient selection and prognosis.
PMID- 25846244
TI - The inhibition the Tet(K) efflux pump of tetracycline resistant Staphylococcus
epidermidis by essential oils from three Salvia species.
AB - The inhibition of efflux pumps is an attractive and powerful response to the
emergence of bacteria resistant to antibiotics. Essential oils (EOs) from Salvia
fruticosa, Salvia officinalis and Salvia sclarea reduce the minimal inhibition
concentration of tetracycline, decrease efflux of antibiotic and decrease the
expression of tet(K) gene in tetracycline resistant clinical isolates of
Staphylococcus epidermidis. In all the cases S. fruticosa was the best one. By
using checkerboard and time-killing methods, we found synergistic interactions of
EOs with tetracycline. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data from
molecular and functional analyses of inhibitory effect of Salvia's essential
oils, namely from S. fruticosa, on Tet(K) pump of Staphylococcus epidermidis and
from modulatory studies may be the starting point for consecutive study of
pharmacokinetic and pharmacodynamic parameters and their perspective use in
combination therapy. Combination of antibiotic with efflux pump inhibitor would
be expected to re-establish susceptibility of the bacteria to antibiotics that
became no longer effective due to bacterial resistance through the efflux pumps.
The inhibition of an efflux pump can potentially improve the clinical efficacy of
an antibiotic and simultaneously decrease the selection of resistant mutants.
PMID- 25846245
TI - Repression of jasmonate signaling by a non-TIFY JAZ protein in Arabidopsis.
AB - JAsmonate ZIM-domain (JAZ) proteins repress the activity of transcription factors
that execute responses to the plant hormone jasmonoyl-L-isoleucine (JA-Ile). The
ZIM protein domain recruits the co-repressors NINJA and TOPLESS to JAZ-bound
transcription factors, and contains a highly conserved TIF[F/Y]XG motif that
defines the larger family of TIFY proteins to which JAZs belong. Here, we report
that diverse plant species contain genes encoding putative non-TIFY JAZ proteins,
including a previously unrecognized JAZ repressor in Arabidopsis (JAZ13, encoded
by At3g22275). JAZ13 is most closely related to JAZ8 and includes divergent EAR,
TIFY/ZIM, and Jas motifs. Unlike JAZ8, however, JAZ13 contains a Ser-rich C
terminal tail that is a site for phosphorylation. Overexpression of JAZ13
resulted in reduced sensitivity to JA, attenuation of wound-induced expression of
JA-response genes, and decreased resistance to insect herbivory. JAZ13 interacts
with the bHLH transcription factor MYC2 and the co-repressor TOPLESS but,
consistent with the absence of a TIFY motif, neither NINJA nor other JAZs.
Analysis of single and higher-order T-DNA insertion jaz null mutants provided
further evidence that JAZ13 is a repressor JA signaling. Our results demonstrate
that proteins outside the TIFY family are functional JAZ repressors and further
suggest that this expansion of the JAZ family allows fine-tuning of JA-mediated
transcriptional responses.
PMID- 25846246
TI - miR-154 suppresses non-small cell lung cancer growth in vitro and in vivo.
AB - miR-154 has been proven to act as a tumor suppressor in several types of tumors.
However, its role in non-small cell lung cancer (NSCLC) remains unclear. Thus,
the aim of this study was to investigate the effects of miR-154 on NSCLC
tumorigenesis and development. Using real-time quantitative PCR (qRT-PCR), we
analyzed expression of miR-154 at the transcriptional level in 40 NSCLC tumor
tissues and matched adjacent normal tissues and the correlation with
clinicopathological features of the patients. The miR-154 mimic was stably
transfected into NSCLC A549 cells, and the effects of miR-154 on cancer cell
proliferation, colony formation, cell cycle arrest, apoptosis, migration and
invasion in vitro, and on the growth of in vivo xenografts were investigated. miR
154 expression levels were significantly downregulated in the NSCLC compared to
the corresponding non-cancerous lung tissues (P<0.05), and decreased miR-154
expression was significantly associated with metastasis (P<0.001), larger tumor
size (P<0.001) and advanced TNM stage (P<0.001). Furthermore, transfection of the
miR-154 mimic into the NSCLC A549 cells was able to inhibit cell proliferation,
colony formation, invasion and migration, and induce cell apoptosis and G0/G1
cell cycle arrest. Enforced expression of miR-154 also suppressed the growth of
cancer cell xenografts in vivo. These findings indicate that miR-154 may become a
potential target for miR-based therapy of NSCLC.
PMID- 25846247
TI - Circumferential type A aortic dissection with intimal intussusception.
AB - A 62-year-old man was admitted to our hospital with sudden chest pain. CT
examination showed the presence of an intimal flap in the aortic root and in the
descending aorta, with no intimal flap in the ascending aorta and curvilinear
filling defects in the aortic arch, and extension into the left subclavian
artery. Surgical treatment consisted of ascending aorta replacement. During the
operation, the intimal tear was found to be circumferential with intussusception
of the intimal layer. The patient died at surgery.
PMID- 25846248
TI - Potential for coronary CT angiography to tailor medical therapy beyond preventive
guideline-based recommendations: insights from the ROMICAT I trial.
AB - BACKGROUND: Coronary CT angiography (CCTA) is used in the emergency department to
rule out acute coronary syndrome in low-intermediate risk patients. OBJECTIVES:
We evaluated the potential of CCTA to tailor aspirin (ASA) and statin therapy in
acute chest pain patients. METHODS: We included all patients in the ROMICAT I
trial who underwent CCTA before admission. Results of CCTA were blinded to
caretakers. We documented ASA and statin therapy at admission and discharge and
determined change in medications during hospitalization, agreement of discharge
medications with contemporaneous guidelines, and agreement with the presence and
severity of coronary artery disease (CAD) as determined by CCTA. RESULTS: We
included 368 patients (53 +/- 12 years; 61% male). Baseline medical therapy at
presentation included 27% on ASA and 24% on statin. Most patients who qualified
for secondary prevention were on ASA and statin therapy at discharge (95% and
80%, respectively), whereas among those qualifying for primary prevention
therapy, only 59% of patients were on aspirin and 33% were on statin at
discharge. Excluding secondary prevention patients, among those with CCTA
detected CAD, only 66/131 (50%) were on ASA at discharge and only 53/131 (40%)
were on statin. Conversely, in those without CCTA-detected CAD, 54/156 (35%) were
on ASA and 20/151 (13%) were on statin at discharge. CONCLUSION: There are
significant discrepancies between discharge prescription of statin and ASA with
the presence and extent of CAD. CCTA presents an efficient opportunity to tailor
medical therapy to CAD in patients undergoing CCTA as part of their acute chest
pain evaluation.
PMID- 25846249
TI - beta-Blocker premedication does not increase the frequency of allergic reactions
from coronary CT angiography: Results from the Advanced Cardiovascular Imaging
Consortium.
AB - BACKGROUND: beta-Blockers are often used for heart rate control during coronary
CT angiography (CTA). Increased frequency and severity of allergic reactions to
radiocontrast media (RCM) have been reported with concomitant use of beta
blockers. OBJECTIVES: The objectives of this study were to determine whether
there is a higher incidence of allergic reactions to low-osmolar nonionic RCM in
patients undergoing coronary CTA with concomitant beta-blockers and to define the
overall incidence and severity of allergic reactions in patients undergoing
coronary CTA with and without a history of allergy to RCM. METHODS: Patients
undergoing coronary CTA at 47 institutions participating in the Advanced
Cardiovascular Imaging Consortium registry were analyzed. The incidence and
severity of allergic reactions were compared between those patients who did and
those who did not receive beta-blockers, as well as in subgroups of patients with
and without a history of prior allergy to RCM. RESULTS: The incidence of allergic
reaction in patients who received beta-blockers was 45 of 23,867 (0.19%) compared
with those who did not receive beta-blockers, which was 9 of 5232 (0.17%; P =
.84; odds ratio = 1.1). Of the patients with history of allergy to RCM, 4 of 706
patients (0.6%) on beta-blockers experienced allergic reactions compared to 1 of
77 patients (1.3%) without beta-blockers (P = .40; odds ratio = 0.43).
CONCLUSIONS: beta-Blocker pretreatment had no effect on the frequency or severity
of allergic reaction in patients undergoing coronary CTA, even in patients with a
past history of allergy to RCM.
PMID- 25846252
TI - Integration of the catalytic subunit activates deneddylase activity in vivo as
final step in fungal COP9 signalosome assembly.
AB - The eight-subunit COP9 signalosome (CSN) is conserved from filamentous fungi to
humans and functions at the interface between cellular signalling and protein
half-life control. CSN consists of six PCI and two MPN domain proteins and forms
a scaffold for additional interacting proteins. CSN controls protein stability in
the ubiquitin-proteasome system where the MPN domain CSN5/CsnE subunit
inactivates cullin-RING ligases. The CSN5/CsnE isopeptidase functions as
deneddylase and removes the ubiquitin-like protein Nedd8. The six PCI domain
proteins of human CSN form a horseshoe-like ring and all eight subunits are
connected by a bundle of C-terminal alpha-helices. We show that single deletions
of any csn subunit of Aspergillus nidulans resulted in the lack of deneddylase
activity and identical defects in the coordination of development and secondary
metabolism. The CSN1/CsnA N-terminus is dispensable for deneddylase activity but
required for asexual spore formation. Complex analyses in mutant strains revealed
the presence of a seven-subunit pre-CSN without catalytic activity.
Reconstitution experiments with crude extracts of deletion strains and
recombinant proteins allowed the integration of CSN5/CsnE into pre-CSN resulting
in an active deneddylase. This supports a stable seven subunit pre-CSN
intermediate where deneddylase activation in vivo can be controlled by CSN5/CsnE
integration as final assembly step.
PMID- 25846251
TI - A randomized controlled trial of treatments for co-occurring substance use
disorders and post-traumatic stress disorder.
AB - BACKGROUND AND AIMS: Post-traumatic stress disorder (PTSD) is common among people
with substance use disorders, and the comorbidity is associated with negative
outcomes. We report on a randomized controlled trial comparing the effect of
integrated cognitive-behavioral therapy (ICBT) plus standard care, individual
addiction counseling plus standard care and standard care alone on substance use
and PTSD symptoms. DESIGN: Three-group, multi-site randomized controlled trial.
SETTING: Seven addiction treatment programs in Vermont and New Hampshire, USA.
PARTICIPANTS/CASES: Recruitment took place between December 2010 and January
2013. In this single-blind study, 221 participants were randomized to one of
three conditions: ICBT plus standard care (SC) (n = 73), individual addiction
counseling (IAC) plus SC (n = 75) or SC only (n = 73). One hundred and seventy
two patients were assessed at 6-month follow-up (58 ICBT; 61 IAC; 53 SC).
Intervention and comparators: ICBT is a manual-guided therapy focused on PTSD and
substance use symptom reduction with three main components: patient education,
mindful relaxation and flexible thinking. IAC is a manual-guided therapy focused
exclusively on substance use and recovery with modules organized in a stage-based
approach: treatment initiation, early abstinence, maintaining abstinence and
recovery. SC are intensive out-patient program services that include 9-12 hours
of face-to-face contact per week over 2-4 days of group and individual therapies
plus medication management. MEASUREMENTS: Primary outcomes were PTSD severity and
substance use severity at 6 months. Secondary outcomes were therapy retention.
FINDINGS: PTSD symptoms reduced in all conditions with no difference between
them. In analyses of covariance, ICBT produced more favorable outcomes on
toxicology than IAC or SC [comparison with IAC, parameter estimate: 1.10;
confidence interval (CI) = 0.17-2.04; comparison with SC, parameter estimate:
1.13; CI = 0.18-2.08] and had a greater reduction in reported drug use than SC
(parameter estimate: -9.92; CI = -18.14 to -1.70). ICBT patients had better
therapy continuation versus IAC (P<0.001). There were no unexpected or study
related adverse events. CONCLUSIONS: Integrated cognitive behavioral therapy may
improve drug-related outcomes in post-traumatic stress disorder sufferers with
substance use disorder more than drug-focused counseling, but probably not by
reducing post-traumatic stress disorder symptoms to a greater extent.
PMID- 25846253
TI - Platelet aggregation values in patients with cardiovascular risk factors are
reduced by verbascoside treatment. A randomized study.
AB - Verbascoside, a phenolic compound, showed several favorable biological
activities, including an antiplatelet activity. No in vivo studies tested its
efficacy and safety in subjects with cardiovascular (CV) factors. The aim of this
randomized, single-center, double-blind, phase II study was to assess the
efficacy and tolerability of verbascoside intake for the modulation of platelet
aggregation (PA) values in subjects with cardiovascular (CV) risk factors. One
hundred subjects with at least one CV risk factor (age >65 years, diabetes
mellitus, hypertension, current cigarettes use, hyperlidemia, waist circumference
>102 cm in male or >88 cm in female) were enrolled and randomly assigned to
receive placebo or verbascoside 50mg or verbascoside 100mg. PA was measured at
baseline and after 2 weeks of study drug assumption, with light transmittance
aggregometry (arachidonic acid, AA, 1 MUM and adenosine diphosphate, ADP, 5 MUM).
Two weeks of treatment with placebo or verbascoside 50mg did not modify PA values
(both after AA and ADP stimuli). On the contrary, after 2 weeks of verbascoside
100mg, PA values decreased significantly (from 51 +/- 13% to 39 +/- 15%, p<0.01
after AA; from 60 +/- 12% to 49 +/- 15%, p = 0.01 after ADP). No serious adverse
events were reported during the study, and no subjects discontinued the study
because of adverse events. We conclude that long-term intake of verbascoside
100mg significantly reduces PA values in subjects with CV risk factors.
PMID- 25846254
TI - Clinical evaluation of an improved cementation technique for implant-supported
restorations: a randomized controlled trial.
AB - BACKGROUND: Cement remnants were frequently associated with peri-implantitis.
Recently, a shoulderless abutment was proposed, raising some concern about cement
excess removal. AIM: To compare different cementation techniques for implant
supported restorations assessing the amount of cement remnants in the peri
implant sulcus. Additional aim was to compare the effect of these cementation
techniques using two different abutment designs. MATERIAL & METHODS: Forty-six
patients requiring double implant-supported restoration in the posterior maxilla
were randomly divided in two groups according to the cementation modality:
intraoral and extraoral. According to the abutment finishing line, implants in
each patient were randomly assigned to shoulderless or chamfer subgroup. In the
intraoral group, crowns were directly seated onto the titanium abutment. In the
extraoral group, crowns were firstly seated onto a resin abutment replica and
immediately removed, then cleansed of the cement excess and finally seated on the
titanium abutment. After cement setting, in both groups, cement excess was
carefully tried to remove. Three months later, framework/abutment complexes were
disconnected and prepared for microscopic analysis: surface occupied by exposed
cement remnants and marginal gaps were measured. Additionally, crown/abutment
complexes were grinded, and voids of cement were measured at abutment/crown
interface. Related-samples Friedman's two-way analysis of variance by ranks was
used to detect differences between groups and subgroups (P <= 0.5). RESULTS: At
the end of the study, a mean value of 0.45 mm2 (+/-0.80), 0.38 mm2 (+/-0.84), and
0.065 mm2 (+/-0.13) and 0.07 mm2 (+/-0.15) described surface occupied by cement
remnants in shoulderless and chamfer abutment with intraoral cementation and
shoulderless and chamfer abutment with extraoral cementation, respectively. A
mean value of 0.40 mm2 (+/-0.377), 0.41 mm2 (+/-0.39) and 0.485 mm2 (+/-0.47) and
0.477 mm2 (+/-0.43) described cement voids at the abutment/crown interface; a
mean value of 0.062 mm (+/-0.03), 0.064 mm (+/-0.35), 0.055 mm (+/-0.016) and
0.054 mm (+/-0.024) described marginal gaps. Statistics showed tendency of
intraoral cementation to have significantly higher cement remnants compared with
abutments with extraoral cementation groups. At the same time, the presence of
voids was significantly higher in case of extraoral cementation. No significant
differences between groups for the variable "gap". CONCLUSIONS: Despite the
presence of more voids, extraoral cementation reduces cement excess. However,
using low adhesivity cement and careful cement removal, a very limited quantity
of cement remnants was observed also in the intraoral cementation.
PMID- 25846250
TI - Biomaterials for Bone Regenerative Engineering.
AB - Strategies for bone tissue regeneration have been continuously evolving for the
last 25 years since the introduction of the "tissue engineering" concept. The
convergence of the life, physical, and engineering sciences has brought in
several advanced technologies available to tissue engineers and scientists. This
resulted in the creation of a new multidisciplinary field termed as "regenerative
engineering". In this article, the role of biomaterials in bone regenerative
engineering is systematically reviewed to elucidate the new design criteria for
the next generation of biomaterials for bone regenerative engineering. The
exemplary design of biomaterials harnessing various materials characteristics
towards successful bone defect repair and regeneration is highlighted. Particular
attention is given to the attempts of incorporating advanced materials science,
stem cell technologies, and developmental biology into biomaterials design to
engineer and develop the next generation bone grafts.
PMID- 25846255
TI - Utility of CMR Markers of Myocardial Injury in Predicting LV Functional Recovery:
Results from PROTECTION AMI CMR Sub-study.
AB - BACKGROUND: Adverse left ventricular (LV) remodelling following acute ST-segment
elevation myocardial infarction (STEMI) has prognostic importance. We aimed to
predict 90-day left ventricular (LV) function following acute STEMI using
variables from clinical presentation, biomarkers, and cardiovascular magnetic
resonance imaging (CMR). METHODS: Consecutive patients undergoing primary
percutaneous coronary intervention for anterior STEMI as part of the Selective
Inhibition of Delta-protein Kinase C for the Reduction of Infarct Size in Acute
Myocardial Infarction (PROTECTION-AMI) trial were enrolled into the CMR sub-study
at selected sites. CMR was performed at baseline (days 3 to 5) and 90 days and
used to evaluate infarct size, myocardial salvage index, infarct heterogeneity,
microvascular obstruction and global LV function. Biochemical markers including
creatinine kinase area under the curve (CK AUC), peak CK, peak CK-myocardial band
(CK-MB) and AUC, and troponin I were collected at specific time-points. RESULTS:
Ninety-six patients were enrolled in the CMR sub study and 85 completed the 90
day follow-up, across 24 centres worldwide. LV ejection fraction (EF) was 56% (46
63%) at baseline and 60% (49-67%) at 90 days (p<0.001). Infarct size had moderate
inverse correlation with 90-day EF (Spearman's rho=-0.7, p < 0.001) and had the
strongest correlation when compared to myocardial salvage index (Spearman's
rho=0.5, p=0.001), infarct heterogeneity (Spearman's rho=-0.4, p=0.02 or
microvascular obstruction (Spearman's rho=-0.4, p<0.001). All biochemical markers
had similar moderate relationship to LVEF at 90 days (Spearman's rho -0.6 to
0.8, p=0.001). In a multivariable model, only baseline LVEF, CMR infarct size and
infarct heterogeneity independently predicted 90-day LVEF. CONCLUSION: This study
reports findings of a combined CMR protocol (including myocardial oedema imaging)
in a multi-centre, multi-vendor setting. We found infarct size, infarct
heterogeneity and myocardial salvage index correlated favourably with 90-day
LVEF, however only the former two were independently predictive.
PMID- 25846256
TI - Incorporation of dried blood alpha fetoprotein into traditional first trimester
Down syndrome screening service.
AB - OBJECTIVE: The aim of this study was to determine whether incorporation of dried
blood alpha fetoprotein (AFP) into first trimester screening using the
biochemical markers free Beta human chorionic gonadotropin (hCG) and pregnancy
associated plasma protein A (PAPP-A) can improve screening performance. METHODS:
A retrospective study of 34 Down syndrome and 1185 unaffected dried blood
specimens. First trimester dried blood AFP was performed using in-house
immunofluorometric time-resolved assay. False positive and detection rates were
determined from modeling. RESULTS: The multiple of the median in Down syndrome
cases was 0.73. At a fixed 5% false positive rate, incorporating AFP into a free
Beta hCG, PAPP-A, and nuchal translucency protocol adds 2% detection resulting in
detection rates of 92% to 94% depending on the gestational age of the blood draw.
At a fixed 90% detection rate, AFP reduced the false positive rate by 1.0 to 1.6
percentage points depending on gestational age. Using a cutoff of 1/1000, the
combination of free beta hCG, PAPP-A, AFP, and nuchal translucency achieved a
detection rate of 96% with a false positive rate of 8.4% to 9.9%. Adding in nasal
bone increased detection to 98% while reducing false positive rates to 4.1% to
4.7%. CONCLUSION: Inclusion of dried blood AFP into traditional first trimester
screening improves detection while optimizing contingent protocols so that cell
free fetal DNA testing may be offered in a more cost effective manner.
PMID- 25846257
TI - Bismuth-lithium bonding in the ion pairs: LiBiL2, where L = a porphyrin or a
salen ligand.
AB - From the reaction between BiCl3 (1 equiv.) and LiN(SiMe3)2 (4 equiv.) and LH2 (2
equiv.), where L = a tetraphenylporphyrin, TPP, an octaethylporphyrin, OEP and
phsalen in THF the title compounds have been obtained LiBiTPP2, LiBiOEP2, and
LiBi(phsalen)2 and LiBi(phsalen)2.THF. Crystals grown from CH2Cl2-hexanes are
colored; (green), (red-purple) and and (red-orange). The molecular structures of
compound , and were determined by single-crystal X-ray crystallography and are
shown to have short LiBi bonds of distance 2.8 A involving the LiL(-)BiL(+).
Compound shows a slipped structure involving Li to two oxygens and a LiBi
distance of 3.1 A. Compounds and undergo a rapid reversible exchange in toluene
d8 at 90 degrees C. The MALDI-MS yields weak molecular ions due to LiBiL2(+/-)
with more intense ions due to BiL(+) and LiL(-) in the positive and negative
modes. The short Li(+) to Bi(3+) distances are comparable to those seen in LiBi
compounds, such a LiBiR2, and are comparable to those seen by Pyykko (P. Pyykko,
J. Phys. Chem. A, 2015, 119, 2326; P. Pyykko and M. Atsumi, Chem. - Eur. J.,
2009, 15, 186; P. Pyykko and M. Atsumi, Chem. - Eur. J., 2009, 15, 12770) for Li
Bi bonds. These can be seen to be involving Bi6s6p hybrid lone-pairs to Li(+)
atoms. The lithium bis(bistrimethylsilyl)amide (2 equiv.) and phsalenH2 in THF
gave a compound having Li2L.2THF, . Crystallographically compound contains two
Li(+) atoms, one coordinated to five atoms LiO2N2.THF. and the other being
coordinated to three atoms, LiO2.THF. By (7)Li and (1)H NMR both lithium atoms
share an equivalent environment.
PMID- 25846258
TI - Fabrication and Characterization of Gd-DTPA-Loaded Chitosan-Poly(Acrylic Acid)
Nanoparticles for Magnetic Resonance Imaging.
AB - Gd-DTPA-loaded chitosan-poly(acrylic acid) nanoparticles (Gd-DTPA@CS-PAA NPs)
were formulated based on the reaction system of water-soluble polymer-monomer
pairs of acrylic acid in chitosan solution followed by sorption of Gd-DTPA.
Morphological investigations revealed the spherical shape of these NPs with about
220 nm particle size. These NPs showed charge reversal characteristic in acidic
solution. In vitro and in vivo magnetic characteristics of these NPs were
explored to estimate their utilization in targeted enhanced magnetic resonance
imaging. Relaxation studies showed that these NPs possessed pH susceptible
relaxation properties, which could introduce in vivo-specific distribution of
contrast agent. MRI experiment showed that these nanoparticles had better results
in contrast enhancement, and the concentration of contrast agent increased in
liver and brain with increment in time. Thus, these NPs could maintain in vivo
long circulation and high relaxation rate and were suitable agents for magnetic
resonance imaging.
PMID- 25846259
TI - In ovo L-arginine supplementation stimulates myoblast differentiation but
negatively affects muscle development of broiler chicken after hatching.
AB - In this study, we tested the hypothesis that in ovo feeding (IOF) of L-arginine
(L-Arg) enhances nitric oxide (NO) production, stimulates the process of
myogenesis, and regulates post-hatching muscle growth. Different doses of L-Arg
were injected into the amnion of chicken embryos at embryonic day (ED) 16. After
hatching, the body weight of individual male chickens was recorded weekly for 3
weeks. During in vitro experiments, myoblasts of the pectoralis major (PM) were
extracted at ED16 and were incubated in medium containing 0.01 mm L-Arg, 0.05 mm
L-Arg, and (or) 0.05 mm L-nitro-arginine-methyl-ester (L-NAME), an inhibitor of
nitric oxide synthase (NOS). When 25 mg/kg L-Arg/initial egg weight was injected,
no difference was observed in body weight at hatch, but a significant decrease
was found during the following 3 weeks compared to that of the non-injected and
saline-injected control, and this also affected the growth of muscle mass. L-NAME
inhibited gene expression of myogenic differentiation antigen (MyoD), myogenin,
NOS, and follistatin, decreased the cell viability, and increased myostatin
(MSTN) gene expression. 0.05 mm L-Arg stimulated myogenin gene expression but
also depressed muscle cell viability. L-NAME blocked the effect of 0.05 mm L-Arg
on myogenin mRNA levels when co-incubated with 0.05 mm L-Arg. L-Arg treatments
had no significant influence on NOS mRNA gene expression, but had inhibiting
effect on follistatin gene expression, while L-NAME treatments had effects on
both. These results suggested that L-Arg stimulated myoblast differentiation, but
the limited number of myoblasts would form less myotubes and then less myofibers,
while the latter limited the growth of muscle mass.
PMID- 25846260
TI - Identification of alkylated phosphates by gas chromatography-mass spectrometric
investigations with different ionization principles of a thermally aged
commercial lithium ion battery electrolyte.
AB - The thermal aging process of a commercial LiPF6 based lithium ion battery
electrolyte has been investigated in view of the formation of volatile phosphorus
containing degradation products. Aging products were analyzed by GC-MS. Structure
determination of the products was performed by support of chemical ionization MS
in positive and negative modes. A fraction of the discovered compounds belongs to
the group of fluorophosphates (phosphorofluoridates) which are in suspect of
potential toxicity. This is well known for relative derivatives, e.g. diisopropyl
fluorophosphate. Another fraction of the identified compounds belongs to the
group of trialkyl phosphates. These compounds may provide a positive impact on
the thermal and electrochemical performance of Li-based batteries as repeatedly
described in the literature.
PMID- 25846261
TI - Simultaneous determination of polar and apolar compounds in environmental samples
by a polyaniline/hydroxyl multi-walled carbon nanotubes composite-coated stir bar
sorptive extraction coupled with high performance liquid chromatography.
AB - Developing novel coatings for stir bar sorptive extraction (SBSE) is essential
for extending the application of SBSE. Herein, a polyaniline/hydroxyl multi
walled carbon nanotubes (PANi/MWCNTs-OH) composite-coated stir bar was prepared
via the adhesion technique for the simultaneous extraction of polar and apolar
compounds, and a novel method of PANi/MWCNTs-OH-coated SBSE coupled with high
performance liquid chromatography-ultraviolet detection (HPLC-UV) was proposed.
To test the extraction performance of PANi/MWCNTs-OH-coated stir bar, phenols,
non-steroidal anti-inflammatory drugs, and polychlorinated biphenyls were
selected as representatives for polar, semi-polar and apolar compounds,
respectively. High enrichment factors (EFs) ranged from 20.4 to 60.4-fold
(theoretical EF, 100-fold) for target analytes were achieved, indicating that the
proposed method is applicable in simultaneous analysis of the compounds with
different polarities. The prepared PANi/MWCNTs-OH-coated stir bar has a good
preparation reproducibility and can be reused for 20 times. The limits of
detection (LODs, S/N=3) were found to be in the range of 0.09-0.81MUg/L. To
validate the applicability, the proposed method was successfully applied to the
analysis of eight target analytes in Yangtze River water after filtration and in
the extract from sediment samples.
PMID- 25846262
TI - Determination of the cardiac drug amiodarone and its N-desethyl metabolite in
sludge samples.
AB - For the first time, a procedure for the simultaneous determination of the
iodinated drug amiodarone and its major metabolite, N-desethylamiodarone, in
sludge from urban sewage treatment plants (STPs) is proposed. Matrix solid-phase
dispersion (MSPD) followed by on-line cationic exchange clean-up, in modular
configuration, was used as sample preparation technique. Liquid chromatography
with tandem mass spectrometry (LC-MS/MS), based on a hybrid quadrupole time-of
flight (QTOF) system, was employed for the selective determination of target
compounds. The optimized procedure provided exhaustive recoveries with little
effect of the sample matrix in the efficiency of electrospray ionization (ESI).
The overall recoveries of the method ranged between 95 and 111%, for samples
spiked at different concentration levels. The achieved limits of quantification
(LOQs) remained below 10ngg(-1) for both compounds, and the linear response range
extended up to 2500ngg(-1). Amiodarone and N-desethylamiodarone were ubiquitous
in sludge samples, from different STPs located in the Northwest of Spain, with
maximum concentrations above 300ngg(-1) referred to the freeze-dried matrix. They
were also present in stabilized sludge (mixed with lime and thermally
dehydrated), which is mostly disposed in agriculture fields as fertilizer.
Furthermore, mono-iodinated analogues of amiodarone and N-desethylamiodarone were
also tentatively identified in some samples from their accurate MS and MS/MS
spectra.
PMID- 25846263
TI - High-performance thin-layer chromatography linked with (bio)assays and mass
spectrometry - a suited method for discovery and quantification of bioactive
components? Exemplarily shown for turmeric and milk thistle extracts.
AB - Extraction parameters, chemical fingerprint, and the single compounds' activity
levels were considered for the selection of active botanicals. For an initial
survey, the total bioactivity (i.e., total reducing capacity, total flavonoids
contents and free radical scavenging capacity) of 21 aqueous and 21 ethanolic
plant extracts was investigated. Ethanolic extracts showed a higher yield and
were further analyzed by HPTLC in detail to obtain fingerprints of single
flavonoids and further bioactive components. Exemplarily shown for turmeric
(Curcuma longa) and milk thistle (Silybum marianum), effect-directed analysis
(EDA) was performed using three selected (bio)assays, the Aliivibrio fischeri
bioassay, the Bacillus subtilis bioassay and the 2,2-diphenyl-1-picrylhydrazyl
(DPPH*) assay. As a proof of principle, the bioactive components found in the
extracts were confirmed by HPTLC-MS. Bioassays in combination with planar
chromatography directly linked to the known, single effective compounds like
curcumin and silibinin. However, also some unknown bioactive components were
discovered and exemplarily characterized, which demonstrated the strength of this
kind of EDA. HPTLC-UV/Vis/FLD-EDA-MS could become a useful tool for selection of
active botanicals and for the activity profiling of the active ingredients
therein. The flexibility in effect-directed detections allows a comprehensive
survey of effective ingredients in samples. This streamlined methodology
comprised a non-targeted, effect-directed screening first, followed by a highly
targeted characterization of the discovered bioactive compounds. HPTLC-EDA-MS can
also be recommended for bioactivity profiling of food on the food intake side, as
not only effective phytochemicals, but also unknown bioactive degradation
products during food processing or contamination products or residues or
metabolites can be detected. Thus, an efficient survey on potential food intake
effects on wellness could be obtained. Having performed both, sum parameter
assays and HPTLC analysis, a comparison of both approaches was made and
discussed.
PMID- 25846265
TI - Mechanical and chemical characterisation of demineralised human dentine after
amalgam restorations.
AB - OBJECTIVES: The purpose of this study was to evaluate the ability of Zn-free vs
Zn-containing amalgams to induce remineralisation at the dentine interface.
METHODOLOGY: Sound and caries-affected dentine surfaces (CAD) were subjected to
both Zn-free and Zn-containing dental amalgam restorations. Dentine surfaces were
studied by nano-indentation, Raman spectroscopy/cluster analysis, X-ray
diffraction (XRD), field emission electron microscope (FESEM) and energy
dispersive analysis (EDX), for mechanical, morphological and chemical
characterisation. Analyses were performed before and after placement amalgam
restorations. RESULTS: Zn-containing amalgams restorations promoted an increase
in the nano-mechanical properties of sound and CAD surfaces. In samples from
sound or CAD restored with Zn-containing amalgams, it was evidenced: (a) new
mineral calcium-phosphate deposits (intratubular and intertubular) with augmented
crystallographic maturity; these crystals were identified as hydroxyl-apatite,
and (b) a generalised crosslinking reduction plus an increase in those values
testing nature and secondary structure of collagen. It indicates an optimal
preservation, molecular organisation and orientation of collagen fibrils.
SIGNIFICANCE: Zn-containing amalgams promote remineralisation of subjacent
dentine, which is more evident in caries affected dentine surfaces.
PMID- 25846264
TI - Efficacy of P188 on lapine meniscus preservation following blunt trauma.
AB - Traumatic injury to the knee leads to the development of post-traumatic
osteoarthritis. The objective of this study was to characterize the effects of a
single intra-articular injection of a non-ionic surfactant, Poloxamer 188 (P188),
in preservation of meniscal tissue following trauma through maintenance of
meniscal glycosaminoglycan (GAG) content and mechanical properties. Flemish Giant
rabbits were subjected to a closed knee joint, traumatic compressive impact with
the joint constrained to prevent anterior tibial translation. The contralateral
limb served as an un-impacted control. Six animals (treated) received an
injection of P188 in phosphate buffered saline (PBS) post trauma, and another six
animals (sham) received a single injection of PBS to the impacted limb.
Histological analyses for GAG was determined 6 weeks post trauma, and functional
outcomes were assessed using stress relaxation micro-indentation. The impacted
limbs of the sham group demonstrated a significant decrease in meniscal GAG
coverage compared to non-impacted limbs (p<0.05). GAG coverage of the impacted
P188 treated limbs was not significantly different than contralateral non
impacted limbs in all regions except the medial anterior (p<0.05). No significant
changes were documented in mechanics for either the sham or treated groups
compared to their respective control limbs. This suggests that a single intra
articular injection of P188 shows promise in prevention of trauma induced GAG
loss.
PMID- 25846266
TI - Deletion of chromosome 8q22.1, a critical region for Nablus mask-like facial
syndrome: four additional cases support a role of genetic modifiers in the
manifestation of the phenotype.
PMID- 25846267
TI - Fibular motor nerve conduction studies: Investigating the mechanism for compound
muscle action potential amplitude drop with proximal stimulation.
AB - INTRODUCTION: The compound muscle action potential (CMAP) amplitude of extensor
digitorum brevis can show a drop with proximal stimulation in normal fibular
nerves. METHODS: We assessed the contribution of the far-field potential recorded
by the reference electrode (R-CMAP) to the fibular CMAP. Negative R-CMAP
amplitude, peak-to-peak amplitude, and negative area were measured and correlated
with the amplitude decrease. Fibular motor nerves from 14 healthy participants
were studied. RESULTS: The mean CMAP amplitude drop with proximal stimulation was
14.0 +/- 9.3%, including a >30% reduction in 1 study. All measured R-CMAP
parameters correlated with the degree of amplitude drop. CONCLUSIONS: A greater R
CMAP contribution to the fibular CMAP leads to greater phase cancellation and
temporal dispersion. The resulting amplitude drop seen in the proximal CMAP can
be large enough to be classified incorrectly as "probable conduction block" by
several different diagnostic criteria.
PMID- 25846269
TI - Cluster coarsening on drops exhibits strong and sudden size-selectivity.
AB - Autophagy, an important process for degradation of cellular components, requires
the targeting of autophagy receptor proteins to potential substrates. Receptor
proteins have been observed to form clusters on membranes. To understand how
receptor clusters might affect autophagy selectivity, we model cluster coarsening
on a polydisperse collection of spherical drop-like substrates. Our model
receptor corresponds to NBR1, which supports peroxisome autophagy. We recover
dynamical scaling of cluster sizes, but find that changing the drop size
distribution changes the cluster-size scaling distribution. The magnitude of this
effect is similar to how changing the spatial-dimension affects scaling in bulk
systems. We also observe a sudden onset of size-selection of the remaining drops
with clusters, due to clusters evaporating from smaller drops and growing on
larger drops. This coarsening-driven size selection provides a physical mechanism
for autophagy selectivity, and may explain reports of size selection during
peroxisome degradation.
PMID- 25846268
TI - Standards of Evidence for Efficacy, Effectiveness, and Scale-up Research in
Prevention Science: Next Generation.
AB - A decade ago, the Society of Prevention Research (SPR) endorsed a set of
standards for evidence related to research on prevention interventions. These
standards (Flay et al., Prevention Science 6:151-175, 2005) were intended in part
to increase consistency in reviews of prevention research that often generated
disparate lists of effective interventions due to the application of different
standards for what was considered to be necessary to demonstrate effectiveness.
In 2013, SPR's Board of Directors decided that the field has progressed
sufficiently to warrant a review and, if necessary, publication of "the next
generation" of standards of evidence. The Board convened a committee to review
and update the standards. This article reports on the results of this committee's
deliberations, summarizing changes made to the earlier standards and explaining
the rationale for each change. The SPR Board of Directors endorses "The Standards
of Evidence for Efficacy, Effectiveness, and Scale-up Research in Prevention
Science: Next Generation."
PMID- 25846270
TI - Rikkunshito induces gastric relaxation via the beta-adrenergic pathway in Suncus
murinus.
AB - BACKGROUND: Rikkunshito (RKT) is a gastroprotective herbal medicine. In this
study, we investigated the role of RKT in the relaxation of the gastric body
(fundus and corpus) and antrum. METHODS: We used Suncus murinus, a unique small
model animal with similar gastrointestinal motility to humans and dogs. RKT was
added at 0.1, 1.0, and 5.0 mg/mL to induce relaxation in vitro; the outcome
measure was the intensity of relaxation. The number of spontaneous antral
contractions in the absence or the presence of RKT was also counted. KEY RESULTS:
Rikkunshito induced the relaxation of the gastric body and antrum and decreased
the number of spontaneous antral contractions in a dose-dependent manner. The
responses to RKT (1.0 mg/mL) were not affected by pretreatment with atropine, N
nitro-l-arginine methyl ester, ritanserin, or ondansetron. On the other hand,
timolol almost completely reversed the relaxation induced by RKT (1.0 mg/mL) on
the gastric body and antrum and the occurrence of the spontaneous antral
contractions. Both butoxamine, a beta(2) -adrenoreceptor antagonist, and L
748337, a beta(3) -adrenoreceptor antagonist, but not CGP 20712, a beta(1)
adrenoreceptor antagonist, significantly reversed the RKT-induced (1.0 mg/mL)
gastric relaxation. CONCLUSIONS & INFERENCES: These results indicate that RKT
stimulates and modulates gastric relaxation through beta(2) - and beta(3)
adrenergic, but not beta(1) -adrenergic, pathways in S. murinus.
PMID- 25846271
TI - RBRIdent: An algorithm for improved identification of RNA-binding residues in
proteins from primary sequences.
AB - Rapid and correct identification of RNA-binding residues based on the protein
primary sequences is of great importance. In most prevalent machine-learning
based identification methods; however, either some features are inefficiently
represented, or the redundancy between features is not effectively removed. Both
problems may weaken the performance of a classifier system and raise its
computational complexity. Here, we addressed the above problems and developed a
better classifier (RBRIdent) to identify the RNA-binding residues. In an
independent benchmark test, RBRIdent achieved an accuracy of 76.79%, Matthews
correlation coefficient of 0.3819 and F-measure of 75.58%, remarkably
outperforming all prevalent methods. These results suggest the necessity of
proper feature description and the essential role of feature selection in this
project. All source data and codes are freely available at
http://166.111.152.91/RBRIdent.
PMID- 25846272
TI - Disulfiram/copper-disulfiram Damages Multiple Protein Degradation and Turnover
Pathways and Cytotoxicity is Enhanced by Metformin in Oesophageal Squamous Cell
Carcinoma Cell Lines.
AB - Disulfiram (DSF), used since the 1950s in the treatment of alcoholism, is
reductively activated to diethyldithiocarbamate and both compounds are thiol
reactive and readily complex copper. More recently DSF and copper-DSF (Cu-DSF)
have been found to exhibit potent anticancer activity. We have previously shown
that the anti-diabetic drug metformin is anti-proliferative and induces an
intracellular reducing environment in oesophageal squamous cell carcinoma (OSCC)
cell lines. Based on these observations, we investigated the effects of Cu-DSF
and DSF, with and without metformin, in this present study. We found that Cu-DSF
and DSF caused considerable cytotoxicity across a panel of OSCC cells, and
metformin significantly enhanced the effects of DSF. Elevated copper transport
contributes to DSF and metformin-DSF-induced cytotoxicity since the cell
impermeable copper chelator, bathocuproinedisulfonic acid, partially reversed the
cytotoxic effects of these drugs, and interestingly, metformin-treated OSCC cells
contained higher intracellular copper levels. Furthermore, DSF may target cancer
cells preferentially due to their high dependence on protein degradation/turnover
pathways, and we found that metformin further enhances the role of DSF as a
proteasome inhibitor. We hypothesized that the lysosome could be an additional,
novel, target of DSF. Indeed, this acid-labile compound decreased lysosomal
acidification, and DSF-metformin co-treatment interfered with the progression of
autophagy in these cells. In summary, this is the first such report identifying
the lysosome as a target of DSF and based on the considerable cytotoxic effects
of DSF either alone or in the presence of metformin, in vitro, and we propose
these as novel potential chemotherapeutic approaches for OSCC.
PMID- 25846273
TI - Predicting pathogen-specific CD8 T cell immune responses from a modeling
approach.
AB - The primary CD8 T cell immune response constitutes a major mechanism to fight an
infection by intra-cellular pathogens. We aim at assessing whether pathogen
specific dynamical parameters of the CD8 T cell response can be identified, based
on measurements of CD8 T cell counts, using a modeling approach. We generated
experimental data consisting in CD8 T cell counts kinetics during the response to
three different live intra-cellular pathogens: two viruses (influenza, vaccinia)
injected intranasally, and one bacteria (Listeria monocytogenes) injected
intravenously. All pathogens harbor the same antigen (NP68), but differ in their
interaction with the host. In parallel, we developed a mathematical model
describing the evolution of CD8 T cell counts and pathogen amount during an
immune response. This model is characterized by 9 parameters and includes
relevant feedback controls. The model outputs were compared with the three data
series and an exhaustive estimation of the parameter values was performed. By
focusing on the ability of the model to fit experimental data and to produce a
CD8 T cell population mainly composed of memory cells at the end of the response,
critical parameters were identified. We show that a small number of parameters (2
4) define the main features of the CD8 T cell immune response and are
characteristic of a given pathogen. Among these parameters, two are related to
the effector CD8 T cell mediated control of cell and pathogen death. The
parameter associated with memory cell death is shown to play no relevant role
during the main phases of the CD8 T cell response, yet it becomes essential when
looking at the predictions of the model several months after the infection.
PMID- 25846275
TI - Cellular aggregate capture by fluidic manipulation device highly compatible with
micro-well-plates.
AB - This paper proposes a capture device to manipulate and transport a cellular
aggregate in a micro-well. A cellular aggregate (a few hundreds MUm in diameter)
is currently manipulated by a pipette. The manual manipulation by a pipette has
problems; low reliability, low throughput, and difficulty in confirmation of task
completion. We took into account of compatibility with existing methods such as a
micro-well-plate and designed for the capture device of a cellular aggregate in a
micro-well. A newly developed capture device flows and carries a cellular
aggregate from a bottom of a well to a trap of the capture device. We designed a
curved surface at the bottom of the capture device to form a space to act as a
channel between the inner wall of the micro-well. This paper presents concept,
design, fabrication, and of the proposed cellular aggregate capture, followed by
successful experimental results.
PMID- 25846274
TI - Juxtamembrane contribution to transmembrane signaling.
AB - Signaling across the cell membrane mediated by transmembrane receptors plays an
important role in diverse biological processes. Recent studies have indicated
that, in a number of single-span transmembrane receptors, the intracellular
juxtamembrane (JM) sequence linking the transmembrane helix with the rest of the
cytoplasmic domain participates directly in the signaling process via several
novel mechanisms. This review briefly highlights several modes of JM dynamics in
the context of signal transduction that are shared by different types of
transmembrane receptors.
PMID- 25846276
TI - Clinical utility estimation for assay cutoffs in early phase oncology enrichment
trials.
AB - Predictive enrichment strategies use biomarkers to selectively enroll oncology
patients into clinical trials to more efficiently demonstrate therapeutic
benefit. Because the enriched population differs from the patient population
eligible for screening with the biomarker assay, there is potential for bias when
estimating clinical utility for the screening eligible population if the
selection process is ignored. We write estimators of clinical utility as
integrals averaging regression model predictions over the conditional
distribution of the biomarker scores defined by the assay cutoff and discuss the
conditions under which consistent estimation can be achieved while accounting for
some nuances that may arise as the biomarker assay progresses toward a companion
diagnostic. We outline and implement a Bayesian approach in estimating these
clinical utility measures and use simulations to illustrate performance and the
potential biases when estimation naively ignores enrichment. Results suggest that
the proposed integral representation of clinical utility in combination with
Bayesian methods provide a practical strategy to facilitate cutoff decision
making in this setting.
PMID- 25846278
TI - Platelet endothelial cell adhesion molecule-1 gene 125C/G polymorphism is
associated with deep vein thrombosis.
AB - Deep vein thrombosis (DVT) is a common disorder that is associated with high
morbidity and mortality. Genetic factors have been suggested to influence the
predisposition towards thrombosis and the incidence of DVT. Platelet endothelial
cell adhesion molecule-1 (PECAM-1) is a key adhesion molecule that is involved in
platelet function and maintenance of endothelial cell junctions. To date, no
studies have examined the association between polymorphisms in PECAM-1 and DVT.
The present study analyzed the single nucleotide polymorphisms (SNPs) of PECAM-1,
namely Leu125Val (C373G), Asn563Ser (T1688C) and Gly670Arg (C2008T), in Chinese
patients with DVT and age-and gender-matched controls, using polymerase chain
reaction-restriction fragment length polymorphism analysis. Furthermore, plasma
soluble PECAM-1 (sPECAM-1) levels were quantified by ELISA. The results of the
present study demonstrated significantly higher genotype and allele frequencies
of the Leu125Val polymorphism in PECAM-1 in the DVT group as compared with those
in the control group (P<0.05). The plasma levels of sPECAM-1 in the DVT group
(83.4 +/- 23.5 ng/ml) were also significantly higher as compared with those in
the control group (60.4 +/- 19.4 ng/ml, P<0.01). In the patients with DVT, plasma
levels of sPECAM-1 were significantly higher in those with the Leu/Val and
Val/Val genotypes as compared with those possessing the Leu/Leu genotype
(P<0.05). The PECAM-1 Leu125Val polymorphism was shown to be associated with an
increased risk of DVT and PECAM-1 protein expression levels in venous vessels. In
patients with DVT, the PECAM-1 Leu/Val and Val/Val genotypes were associated with
delayed thrombus resolution, as determined by thrombus scoring, as compared with
that in patients possessing the Leu/Val genotype. In conclusion, the present
study indicated that PECAM-1 Leu125Val polymorphism and sPECAM-1 levels may be
associated with DVT.
PMID- 25846277
TI - Downregulation of CRNN gene and genomic instability at 1q21.3 in oral squamous
cell carcinoma.
AB - OBJECTIVES: This study includes the direct sequencing of cornulin (CRNN) gene to
elucidate the possible mechanism of CRNN downregulation and explore the genetic
imbalances at 1q21.3 across oral squamous cell carcinoma (OSCC) samples.
MATERIALS AND METHODS: In mutation screening of CRNN gene, gDNA from OSCC tissues
were extracted, amplified, and followed by direct sequencing. OSCC samples were
also subjected to fragment analysis on CRNN gene to investigate its
microsatellite instability (MSI) and loss of heterozygosity (LOH).
Immunohistochemistry was performed to validate CRNN downregulation in OSCC
samples. RESULTS: No pathogenic mutation was found in CRNN gene, while high
frequency of allelic imbalances was found at 1q21.3 region. MSI was found more
frequent (25.3 %) than LOH (9.3 %). Approximately 22.6 % of cases had high MSI
which reflects higher probability of inactivation of DNA mismatch repair genes.
MSI showed significant association with no betel quid chewing (p = 0.003) and
tongue subsite (p = 0.026). LOH was associated with ethnicity (p = 0.008) and
advanced staging (p = 0.039). The LOH at 1q21.3 was identified to be as an
independent prognostic marker in OSCC (HRR = 7.15 (95 % CI, 1.41-36.25), p =
0.018). Downregulation of CRNN was found among MSI-positive OSCCs and was
associated with poor prognosis (p = 0.044). CONCLUSION: This study showed a
significant correlation between LOH/MSI at 1q21.3 with clinical outcomes and that
downregulation of CRNN gene could be considered as a prognostic marker of OSCC.
CLINICAL RELEVANCE: Insights of the downregulation mode of CRNN gene lays the
basis of drug development on this gene as well as revealing its prognostic value.
PMID- 25846279
TI - Reply.
PMID- 25846286
TI - Candida arteritis in kidney transplant recipients: case report and review of the
literature.
AB - Multi-organ procurement is a risk factor for contamination of preservation fluid
with intestinal flora including fungi (e.g., Candida). Transmission of fungal
species to the graft vessel can cause mycotic arteritis. This is a very rare but
life-threatening complication of renal transplantation. We present 2 cases of
renal transplant recipients from the same multi-organ donor. Both recipients
suffered from severe hemorrhages from renal graft anastomosis and renal artery
pseudoaneurysm due to Candida albicans arteritis (CAA). The culture of the
preservation fluid revealed growth of Escherichia coli, but neither preservation
fluid nor multiple routine blood cultures performed before hemorrhagic
complications revealed fungal growth (media non-selective for fungal growth were
applied). The first recipient suffered from sudden severe hemorrhage in the area
of graft anastomosis on day 10 post surgery (without any preceding clinical or
radiological symptoms). This led to urgent surgery and graftectomy, which was
complicated by cardio-respiratory arrest with resuscitation in the operating
room; despite resuscitation, irreversible brain damage, and subsequent death
occurred in the intensive care unit (ICU) 2 weeks later (on day 24 after
transplantation). The second patient underwent urgent vascular surgery on day 22
(after transplantation), because of hemorrhage from a pseudoaneurysm of the graft
artery. She required repeated vascular operations, extended antimicrobial and
antifungal therapy, and ICU monitoring and, despite these interventions, she died
on day 80 after transplantation as a result of Pseudomonas aeruginosa sepsis.
Arteritis of the renal artery in both patients was caused by C. albicans. This
was confirmed by histopathology: infiltration of renal artery with budding yeast
forming pseudohyphae (Case 1), and the presence of C. albicans in the culture of
the renal artery and surrounding tissue (Case 2). We conclude that organ
preservation solution should be cultured with use of media selective for fungal
growth. As soon as the positive culture is detected, appropriate measures
protecting patients against CAA should be undertaken.
PMID- 25846289
TI - Getting it first versus getting it right: weighing the value of and evidence for
progression-free survival as a surrogate endpoint for overall survival in
glioblastoma.
PMID- 25846288
TI - Unsanctifying the sanctuary: challenges and opportunities with brain metastases.
AB - While the use of targeted therapies, particularly radiosurgery, has broadened
therapeutic options for CNS metastases, patients respond minimally and prognosis
remains poor. The inability of many systemic chemotherapeutic agents to penetrate
the blood-brain barrier (BBB) has limited their use and allowed brain metastases
to become a burgeoning clinical challenge. Adequate preclinical models that
appropriately mimic the metastatic process, the BBB, and blood-tumor barriers
(BTB) are needed to better evaluate therapies that have the ability to enhance
delivery through or penetrate into these barriers and to understand the
mechanisms of resistance to therapy. The heterogeneity among and within different
solid tumors and subtypes of solid tumors further adds to the difficulties in
determining the most appropriate treatment approaches and methods of laboratory
and clinical studies. This review article discusses therapies focused on
prevention and treatment of CNS metastases, particularly regarding the BBB, and
the challenges and opportunities these therapies present.
PMID- 25846291
TI - Dengue seroprevalence in the French West Indies: a prospective study in adult
blood donors.
AB - Using an anti-dengue immunoglobulin G (IgG) indirect enzyme-linked immunosorbent
assay, seroprevalence was determined among 783 adult blood donors in the French
Caribbean islands of Guadeloupe and Martinique in 2011. Overall, 93.5% [91.5;
95.1] samples were positive for dengue antibodies, 90.7% (350 of 386) in
Martinique and 96.2% (382 of 397) in Guadeloupe. Only 30% of these adults
recalled having had dengue disease before. Serotype-specific neutralization
assays applied to a subset of IgG-positive samples indicated that a majority (77
of 96; 80%) reacted to the four serotypes. These seroprevalence findings are the
first reported for Guadeloupe and Martinique and are consistent with the dengue
epidemiology in these territories.
PMID- 25846292
TI - Persistent strongyloidiasis complicated by recurrent meningitis in an HTLV
seropositive Peruvian migrant resettled in Italy.
AB - We describe a case of persistent strongyloidiasis complicated by recurrent
meningitis, in a human T cell lymphotropic virus type 1 (HTLV-1) seropositive
Peruvian migrant adult resettled in Italy. He was admitted with signs and
symptoms of acute bacterial meningitis, reporting four other meningitis episodes
in the past 6 years, with an etiological diagnosis of Escherichia coli and
Enterococcus faecium in two cases. He had been previously treated with several
antihelmintic regimens not including ivermectin, without eradication of
strongyloidiasis, and he had never been tested for HTLV before. During the
described episode, the patient was treated for meningitis with broad-spectrum
antibiotic therapy and 200 MUg/kg/dose oral ivermectin once daily on day 1, 2, 15
and 16 with full recovery and no further episodes of meningitis. The presented
case underlines several critical points concerning the management of poorly known
neglected diseases such as strongyloidiasis and HTLV infection in low-endemic
areas. Despite several admissions for meningitis and strongyloidiasis, the
parasitic infection was not adequately treated and the patient was not previously
tested for HTLV. The supply of ivermectin and the choice of treatment scheme was
challenging since ivermectin is not approved in Italy and there are no
standardized guidelines for the treatment of severe strongyloidiasis in HTLV
seropositive subjects.
PMID- 25846294
TI - The post-2015 development agenda: keeping our focus on the worst off.
AB - Non-communicable diseases now account for the majority of the global burden of
disease and an international campaign has emerged to raise their priority on the
post-2015 development agenda. We argue, to the contrary, that there remain strong
reasons to prioritize maternal and child health. Policy-makers ought to assign
highest priority to the health conditions that afflict the worst off. In virtue
of how little healthy life they have had, children who die young are among the
globally worst off. Moreover, many interventions to deal with the conditions that
cause mortality in the young are low-cost and provide great benefits to their
recipients. Consistent with the original Millennium Development Goals, the
international community should continue to prioritize reductions in communicable
diseases, neonatal conditions, and maternal health despite the shifts in the
global burden of disease.
PMID- 25846293
TI - Needs, acceptability, and value of humanitarian medical assistance in remote
Peruvian Amazon riverine communities.
AB - Much debate exists regarding the need, acceptability, and value of humanitarian
medical assistance. We conducted a cross-sectional study on 457 children under 5
years from four remote riverine communities in the Peruvian Amazon and collected
anthropometric measures, blood samples (1-4 years), and stool samples. Focus
groups and key informant interviews assessed perspectives regarding medical aid
delivered by foreigners. The prevalence of stunting, anemia, and intestinal
parasites was 20%, 37%, and 62%, respectively. Infection with multiple parasites,
usually geohelminths, was detected in 41% of children. The prevalence of
intestinal parasites both individual and polyparasitism increased with age.
Participants from smaller communities less exposed to foreigners expressed lack
of trust and fear of them. However, participants from all communities were
positive about foreigners visiting to provide health support. Prevalent health
needs such as parasitic infections and anemia may be addressed by short-term
medical interventions. There is a perceived openness to and acceptability of
medical assistance delivered by foreign personnel.
PMID- 25846295
TI - Trichinellosis in Vietnam.
AB - Trichinellosis is a zoonotic parasitic disease with a worldwide distribution. The
aim of this work was to describe the epidemiological and clinical data of five
outbreaks of trichinellosis, which affected ethnic minorities living in remote
mountainous areas of northwestern Vietnam from 1970 to 2012. Trichinellosis was
diagnosed in 126 patients, of which 11 (8.7%) were hospitalized and 8 (6.3%)
died. All infected people had consumed raw pork from backyard and roaming pigs or
wild boar at wedding, funeral, or New Year parties. The short incubation period
(average of 9.5 days), the severity of the symptoms, which were characterized by
diarrhea, abdominal pain, fever, myalgia, edema, weight loss, itch, and lisping,
and the high mortality, suggest that patients had ingested a high number of
larvae. The larval burden in pigs examined in one of the outbreaks ranged from 70
to 879 larvae/g. These larvae and those collected from a muscle biopsy taken from
a patient from the 2012 outbreak were identified as Trichinella spiralis. Data
presented in this work show that the northern regions of Vietnam are endemic
areas for Trichinella infections in domestic pigs and humans.
PMID- 25846296
TI - 2013 dengue outbreaks in Singapore and Malaysia caused by different viral
strains.
AB - Characterization of 14,079 circulating dengue viruses in a cross-border
surveillance program, UNITEDengue, revealed that the 2013 outbreaks in Singapore
and Malaysia were associated with replacement of predominant serotype. While the
predominant virus in Singapore switched from DENV2 to DENV1, DENV2 became
predominant in neighboring Malaysia. Dominance of DENV2 was most evident on the
southern states where higher fatality rates were observed.
PMID- 25846297
TI - Use of eCompliance, an innovative biometric system for monitoring of tuberculosis
treatment in rural Uganda.
AB - Directly observed therapy short-course (DOTS) requires direct observation of
tuberculosis (TB) patients and manual recording of doses taken. Programmatically,
manual tracking is both time-consuming and prone to human error. Our project in
western Uganda assessed the impact on TB treatment outcomes of a comprehensive
patient support program including eCompliance, a biometric medical record device,
with the aim of increasing TB patient retention. Through an observational study
of 142 patients, DOTS outcomes of patients in the intervention group were
compared with two control groups. Descriptive statistical comparisons, case
cohort analysis, and difference in change over time were used to assess the
impact. Intervention patients had a higher cure rate than all other patients
(55.6% versus 28.3% [P < 0.01]) and the odds of having a "cured" outcome were
3.17 higher (P < 0.05). The intervention group had a statistically significantly
lower odds of having a negative outcome (0% versus.17% [P < 0.01]) than patients
from the control groups. Additionally, the intervention group had a lost to
follow-up rate lower than all other groups (0% versus 7%) that was trending on
significant. In resource-limited settings, implementing comprehensive DOTS
including eCompliance may reduce the occurrence of negative DOTS outcomes for
patients.
PMID- 25846298
TI - Determinants of societal costs in Alzheimer's disease: GERAS study baseline
results.
AB - BACKGROUND: To identify the main factors associated with societal costs of
Alzheimer's disease (AD) in community-dwelling patients across three European
countries. METHODS: Baseline cost data from a prospective, observational study
were used. Assessments included patients' cognition, activities of daily living
(ADLs) and behavioral symptoms, and caregiver burden. Cost calculations (2010)
from the societal perspective were based on patient/caregiver resource use.
Generalized linear models estimated factors associated with costs. RESULTS: Mean
monthly costs per patient differed for France (?1881), Germany (?2349), and the
UK (?2016), with informal care costs accounting for 50% to 61%. Independent
factors associated with costs across all countries were ADL total score, patient
living arrangements, caregiver working status, and caregiver burden (all P <
.05). Additional factors were significant for the pooled cohort or individual
countries. CONCLUSIONS: Several patient and caregiver factors, including factors
associated with informal care, should be included when evaluating care options
for patients with AD.
PMID- 25846300
TI - In vivo processing and release into the circulation of GFP fusion protein in
arginine vasopressin enhanced GFP transgenic rats: response to osmotic
stimulation.
AB - Arginine vasopressin (AVP) is a neurohypophysial hormone synthesized as a part of
a prepropeptide precursor containing the signal peptide, AVP hormone, AVP
associated neurophysin II and copeptin in the hypothalamic neurosecretory
neurons. A transgenic (Tg) rat line expressing the AVP-eGFP fusion gene has been
generated. To establish the AVP-eGFP Tg rat as a unique model for an analysis of
AVP dynamics in vivo, we first examined the in vivo molecular dynamics of the AVP
eGFP fusion gene, and then the release of GFP in response to physiological
stimuli. Double immunoelectron microscopy demonstrated that GFP was specifically
localized in neurosecretory vesicles of AVP neurons in this Tg rat. After
stimulation of the posterior pituitary with high potassium we demonstrated the
exocytosis of AVP neurosecretory vesicles containing GFP at the ultrastructural
level. Biochemical analyses indicated that the AVP-eGFP fusion gene is subjected
to in vivo post-translational modifications like the native AVP gene, and is
packaged into neurosecretory vesicles as a fusion protein: copeptin1-14 -GFP.
Moreover, GFP release into the circulating blood appeared to be augmented after
osmotic stimulation, like native AVP. Thus, here we show for the first time the
in vivo molecular processing of the AVP-eGFP fusion gene and stimulated secretion
after osmotic stimulation in rats. Because GFP behaved like native AVP in the
hypothalamo-pituitary axis, and in particular was released into the circulation
in response to a physiological stimulus, the AVP-eGFP Tg rat model appears to be
a powerful tool for analyzing neuroendocrine systems at the organismal level.
PMID- 25846301
TI - Ritonavir-boosted protease inhibitor based therapy: a new strategy in chronic
hepatitis C therapy.
AB - Chronic hepatitis C virus (HCV) infection is a worldwide health issue. All oral
therapies are quickly replacing peg-interferon-based treatment regimens.
Developing effective, well tolerated, treatments accessible for difficult to
treat populations remains an unmet need. Ritonavir, an HIV-1 protease inhibitor,
has pharmacokinetic properties that enhance the activity of concomitantly
administered direct acting antivirals against HCV. Ritonavir inhibits Cytochrome
P450 isozyme 3A4, diminishing first pass effect and hepatic metabolism, changing
the pharmacokinetic parameters of Cytochrome P450 isozyme 3A4 substrates. When
combined with the HCV protease inhibitor paritaprevir, ritonavir increases mean
area under the curve, allowing once daily dosing. While Phase II and III clinical
trials with ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir
demonstrated high efficacy in those with HCV infection, drug-drug interactions
warrant cautious use of ritonavir in specific patient populations. Consideration
of the patients' full medication list is imperative due to the ubiquitous nature
of the Cytochrome P450 isozyme 3A4 system.
PMID- 25846299
TI - The aqueous phase of Alzheimer's disease brain contains assemblies built from ~4
and ~7 kDa Abeta species.
AB - INTRODUCTION: Much knowledge about amyloid beta (Abeta) aggregation and toxicity
has been acquired using synthetic peptides and mouse models, whereas less is
known about soluble Abeta in human brain. METHODS: We analyzed aqueous extracts
from multiple AD brains using an array of techniques. RESULTS: Brains can contain
at least four different Abeta assembly forms including: (i) monomers, (ii) a ~7
kDa Abeta species, and larger species (iii) from ~30-150 kDa, and (iv) >160 kDa.
High molecular weight species are by far the most prevalent and appear to be
built from ~7 kDa Abeta species. The ~7 kDa Abeta species resist denaturation by
chaotropic agents and have a higher Abeta42/Abeta40 ratio than monomers, and are
unreactive with antibodies to Asp1 of Ab or APP residues N-terminal of Asp1.
DISCUSSION: Further analysis of brain-derived ~7 kDa Abeta species, the mechanism
by which they assemble and the structures they form should reveal therapeutic and
diagnostic opportunities.
PMID- 25846302
TI - Transperineal ultrasonography for labor management: accuracy and reliability.
AB - OBJECTIVE: To compare ultrasound measurements and clinical assessments of
cervical dilatation, fetal head station and fetal head position. DESIGN:
Prospective, observational study. SETTING: Tertiary care center (Ankara
University Hospital), labor ward. POPULATION: Forty-three women in labor.
METHODS: Women were prospectively evaluated through simultaneous examinations (79
in total). Dilatation, head station, and position were recorded via digital
examination whenever possible and were compared with ultrasonographic
measurements of dilatation, angle of progression, head-perineum distance, and
head position by two independent operators. Operators were blinded to each
other's findings. MAIN OUTCOME MEASURES: Agreement between sonographic
measurements and digital examinations. RESULTS: Ultrasonographic assessment of
dilatation correlated significantly with digital examination. The interclass
correlation coefficient of the two methods was 0.82 (95% confidence interval 0.73
0.88). Ultrasonography showed a mean lower cervical dilatation of 10 mm (95%
limits of agreement: -36 to 16 mm) compared with digital examination. The angle
of progression and head-perineum distances correlated moderately with the
palpated head station (Pearson's correlation coefficients: 0.55 and -0.42,
respectively; p < 0.001). Position could only be assessed in 40 of 79
examinations by digital examinations and the results showed low agreement with
ultrasound findings. CONCLUSION: We observed good agreement between clinical and
ultrasound assessment of dilatation, moderate agreement in assessing fetal
station and low agreement assessing head position.
PMID- 25846303
TI - An aberration-corrected STEM study of structural defects in epitaxial GaN thin
films grown by ion beam assisted MBE.
AB - Ion-beam assisted molecular-beam epitaxy was used for direct growth of epitaxial
GaN thin films on super-polished 6H-SiC(0001) substrates. The GaN films with
different film thicknesses were studied using reflection high energy electron
diffraction, X-ray diffraction, cathodoluminescence and primarily aberration
corrected scanning transmission electron microscopy techniques. Special attention
was devoted to the microstructural characterization of GaN thin films and the GaN
SiC interface on the atomic scale. The results show a variety of defect types in
the GaN thin films and at the GaN-SiC interface. A high crystalline quality of
the produced hexagonal GaN thin films was demonstrated. The gained results are
discussed.
PMID- 25846304
TI - Electronic structure of MgS and MgYb2S4: Electron Energy-Loss Spectroscopy and
self-consistent multiple scattering calculations.
AB - The electronic structure of MgS and MgYb2S4 have been studied using the fine
structure of the Mg-K, S-K, Mg-L2,3, S-L2,3 and Yb-N5 edges measured by electron
energy-loss spectroscopy (EELS). Our experimental results are compared with real
space full multiple scattering calculations as incorporated in the FEFF9.6 code.
All edges are very well reproduced. Total and partial densities of states have
been calculated. The calculated densities of states of Mg and S are similar in
both compounds. The energy distribution of these states suggests a covalent
nature for both materials. For MgYb2S4 a band gap smaller than for MgS is
predicted. In this compound the top of the valence band and the bottom of the
conduction band are dominated by Yb states.
PMID- 25846305
TI - Physical activity and academic achievement in a Swedish elementary school.
PMID- 25846306
TI - Kall, Linden, and Nilsson respond: the impact of a physical activity intervention
program on academic achievement.
PMID- 25846307
TI - Out-of-school time activity participation among US--immigrant youth.
AB - BACKGROUND: Structured out-of-school time (OST) activities are associated with
positive academic and psychosocial outcomes. METHODS: Data came from the 2007
National Survey of Children's Health, restricted to 36,132 youth aged 12-17
years. Logistic regression models were used to examine the joint effects of
race/ethnicity and immigrant family type on the participation in OST activities.
RESULTS: Compared with US-born (USB) non-Hispanic White youth with USB parents,
USB Hispanic youth with USB parents were less likely to participate in sports,
whereas non-Hispanic Black youth with immigrant parents were more likely to
participate in sports. White youth with at least 1 immigrant parent had higher
odds of participating in after-school clubs. All Hispanic youth were less likely
to participate in after-school clubs. USB Hispanic youth, USB Black youth, and
White youth and "other" youth with at least 1 immigrant parent had higher odds of
engaging in community services. Youth from immigrant families had lower odds of
doing paid work. CONCLUSIONS: Hispanic youth were less likely to participate in
OST activities. Non-Hispanic youth with immigrant parents did not engage in fewer
OST activities compared with USB White youth with USB parents. Intervention and
recruitment strategies for OST activities may need to be customized for immigrant
groups.
PMID- 25846309
TI - Longitudinal changes in beliefs by stage of physical activity adoption in Iranian
girls.
AB - BACKGROUND: The aims of this study were to examine the relationships among
physical activity (PA)-related beliefs and to determine to what extent Iranian
adolescents in different stages of PA adoption differ in perceived benefits and
barriers during a 3-year transition from junior high school to high school.
METHODS: Data were collected from female adolescents in 2010 (N = 558), of whom
412 provided follow-up data in 2013. One-way analysis of variance and logistic
regression were conducted for statistical analysis. RESULTS: Participants in the
action and maintenance stages reported the greatest agreement with benefits. Pre
contemplators were about 4 times more likely to cite "not enough time" than
preparers (OR = 3.95). Pre-contemplators were over 4 times more likely to cite
not liking exercise than those in action and maintenance stages at baseline (OR =
4.32 and 4.85), a finding which was maintained at follow-up (OR = 3.66 and 8.65).
CONCLUSIONS: These findings could help with the creation of interventions
tailored to encourage pre-contemplators to progress toward adoption of PA.
Providing transportation supports, enhancing time management, and mitigating
boredom may be helpful strategies either to prevent relapse in adoption stages or
to move females in early stages of change toward action and maintenance.
PMID- 25846308
TI - Investigating stakeholder attitudes and opinions on school-based human
papillomavirus vaccination programs.
AB - BACKGROUND: In several countries worldwide, school-based human papillomavirus
(HPV) vaccination programs have been successful; however, little research has
explored US stakeholders' acceptance toward school-based HPV vaccination
programs. METHODS: A total of 13 focus groups and 12 key informant interviews (N
= 117; 85% females; 66% racial/ethnic minority) were conducted with 5 groups of
stakeholders: parents of adolescent girls, parents of adolescent boys, adolescent
girls, middle school nurses, and middle school administrators throughout the 5
public health regions of New Mexico. RESULTS: All groups of stakeholders lacked
knowledge on HPV and HPV vaccines. Stakeholders were interested in--but
apprehensive about--the benefits of HPV vaccination. Despite previous literature
showing the benefits of using middle schools as an HPV vaccination site,
stakeholders did not deem middle schools as a viable site for vaccination. Nurses
reported that using the school as an HPV vaccination site had not occurred to
them; parents and adolescents stated they were uncertain about using this type of
program. School administrators indicated that they lacked implementation
authority. CONCLUSIONS: Our study uncovered barriers to using middle schools as a
site of HPV vaccination. Resources should be directed toward increased support
and education for middle school nurses who function as opinion leaders relevant
to the uptake of HPV vaccination.
PMID- 25846310
TI - From the school health education study to the national health education
standards: concepts endure.
AB - BACKGROUND: The landmark School Health Education Study (SHES) project influenced
by the conceptual approach to teaching and learning provides perspective on
modern school health instruction. Conceptual education, the cornerstone of the
SHES curriculum framework (CF), Health Education: A Conceptual Approach to
Curriculum Design, fosters a student's understanding of information that develops
with experience. METHODS: Data were collected through content analysis of the
SHES CF and the National Health Education Standards: Achieving Excellence (NHES),
2nd edition. Similarity of essential framework elements was established. Inter
rater reliability was established. RESULTS: Alignment of the SHES components with
the NHES reveals parallel conceptual structures around which to develop
curriculum. CONCLUSIONS: The conceptual approach to curriculum planning has
enduring value. It provides a foundation for teaching and learning that is
adaptable, flexible, and can maintain permanence in conjunction with emerging
scientific evidence and cultural and political influences on health behavior.
PMID- 25846311
TI - High school students' experiences of bullying and victimization and the
association with school health center use.
AB - BACKGROUND: Bullying and victimization are ongoing concerns in schools. School
health centers (SHCs) are well situated to support affected students because they
provide crisis intervention, mental health care, and broader interventions to
improve school climate. This study examined the association between urban
adolescents' experiences of school-based bullying and victimization and their use
of SHCs. METHODS: Data was analyzed from 2063 high school students in 5 Northern
California school districts using the 2009-2010 California Healthy Kids Survey.
Chi-square tests and multivariate logistic regression were used to measure
associations. RESULTS: Students who were bullied or victimized at school had
significantly higher odds of using the SHCs compared with students who were not,
and were also significantly more likely to report confidentiality concerns. The
magnitude of associations was largest for Asian/Pacific Islander students, though
this was likely due to greater statistical power. African American students
reported victimization experiences at approximately the same rate as their peers,
but were significantly less likely to indicate they experienced bullying.
CONCLUSIONS: Findings suggest that SHCs may be an important place to address
bullying and victimization at school, but confidentiality concerns are barriers
that may be more common among bullied and victimized youth.
PMID- 25846312
TI - Comparison of height, weight, and body mass index data from state-mandated school
physical fitness testing and a districtwide surveillance project.
AB - BACKGROUND: Approximately one third of California school-age children are
overweight or obese. Legislative approaches to assessing obesity have focused on
school-based data collection. During 2010-2011, the Chula Vista Elementary School
District conducted districtwide surveillance and state-mandated physical fitness
testing (PFT) among fifth grade students. We compared height, weight, and body
mass index (BMI) to examine measurement differences between the projects.
METHODS: We assessed demographic characteristics and BMI category frequencies. We
used paired t-tests to test continuous variables. kappa statistics were used to
assess categorical agreement. RESULTS: Of 3549 children assessed, 69% were
Hispanic. Fifty-one percent were boys. Mean heights, weights, and BMIs were
significantly different for each project (p < .0001). Surveillance height (106.7
165.1 cm) and weight (21.6-90.8 kg) ranges were lesser than PFT ranges (109.2
180.3 cm and 22.7-98.4 kg). The overall BMI category agreement was good (weighted
kappa = 0.77). Categorical percentage agreement was highest among normal weight
children (94.9%) and lowest among underweight children (56.6%). CONCLUSIONS:
Methodological differences might have resulted in the observed height, weight,
and BMI differences. As school-based interventions become common, districts
should carefully consider measurement reliability, training, and data-handling
protocols to have confidence in their findings.
PMID- 25846313
TI - Coping and survival skills: the role school personnel play regarding support for
bullied sexual minority-oriented youth.
AB - BACKGROUND: Research has shown that bullying has serious health consequences, and
sexual minority-oriented youth are disproportionately affected. Sexual minority
oriented youth include lesbian, gay, bisexual, transgender, queer, or questioning
(LGBTQ) individuals. This study examined the bullying experiences of sexual
minority-oriented youth in a predominantly rural area of a Midwestern state. The
purpose of this study was to have bullied youth describe their experiences and to
present their perspectives. METHODS: Using critical qualitative inquiry, 16 in
depth interviews were conducted in-person or online with youth, ages 15-20, who
self-identified as having been bullied based on their perceived minority sexual
orientation status. RESULTS: The role of supportive school personnel was found to
be meaningful, and supportive school personnel were mentioned as assisting with
the coping and survival among this group of bullied sexual minority youth.
CONCLUSIONS: Supportive school personnel are crucial to the coping and survival
of these youth. All school personnel need to be aware of the anti-bullying
policies in their school corporations. They may then work to strengthen and
enforce their policies for the protection of bullied youth.
PMID- 25846314
TI - Creating a school-based eye care program.
PMID- 25846315
TI - Posterior Shoulder Instability in Throwing Athletes: A Case-Matched Comparison of
Throwers and Non-Throwers.
AB - PURPOSE: To evaluate the results of arthroscopic capsulolabral repair for the
treatment of posterior shoulder instability in a throwing athlete cohort when
compared with non-throwers. METHODS: Forty-eight overhead-throwing athletes
undergoing arthroscopic posterior capsulolabral reconstruction were case matched
with 48 non-throwing athletes. These cohorts were followed as they underwent
posterior capsulolabral reconstruction by measuring shoulder pain, function,
return to sport, and operative failures. Operative details such as intra
articular pathology and repair construct were also recorded. RESULTS: At a mean
follow-up of 37 months (range, 12 to 97 months) postoperatively, no statistical
differences were noted between throwers and non-throwers regarding American
Shoulder and Elbow Surgeons scores, stability, strength, or range of motion.
Sixty percent of throwing athletes were able to return to their preinjury level
of competitive throwing. Throwers with a discrete labral tear intraoperatively
had a 10-fold increased likelihood of returning to sport (odds ratio, 9.6; P =
.012). Similarly, throwers who had suture anchor constructs showed a 10-fold
increased likelihood of returning to play compared with anchor-less repairs (odds
ratio, 9.6; P = .012). Non-throwers showed no variability by labral findings or
fixation techniques. Pitchers had equivocal outcome scores when compared with
other throwers but had poorer return-to-play rates (50% v 60% full return).
CONCLUSIONS: Arthroscopic capsulolabral plication for unidirectional posterior
shoulder instability is an effective treatment for overhead-throwing athletes.
Intraoperatively, achieving an adequate capsular plication and stabilizing the
repair with suture anchors will give this athletic population the best odds of
returning to competitive sports. LEVEL OF EVIDENCE: Level III, retrospective
comparative study.
PMID- 25846316
TI - Honokiol suppresses metastasis of renal cell carcinoma by targeting KISS1/KISS1R
signaling.
AB - Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known
to have a high risk of metastasis, which is considered responsible for more than
90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated
from Magnolia spp. bark and has been shown to be a potential anticancer agent
involved in multiple facets of signal transduction. In this study, we
demonstrated that honokiol inhibited the invasion and colony formation of highly
metastatic RCC cell line 786-0 in a dose-dependent manner. DNA-microarray data
showed the significant upregulation of metastasis-suppressor gene KISS1 and its
receptor, KISS1R. The upregulation was confirmed by qRT-PCR analysis.
Overexpression of KISS1 and KISS1R was detected by western blotting at the
translation level as well. Of note, the decreased invasive and colonized
capacities were reversed by KISS1 knockdown. Taken together, the results first
indicate that activation of KISS1/KISS1R signaling by honokiol suppresses
multistep process of metastasis, including invasion and colony formation, in RCC
cells 786-0. Honokiol may be considered as a natural agent against RCC
metastasis.
PMID- 25846317
TI - Noonan syndrome-like disorder with loose anagen hair: a second case with
neuroblastoma.
AB - Noonan-like syndrome with loose anagen hair (NSLH), also known as Mazzanti
syndrome, is a RASopathy characterized by craniofacial features resembling Noonan
syndrome, cardiac defects, cognitive deficits and behavioral issues, reduced
growth generally associated with GH deficit, darkly pigmented skin, and an unique
combination of ectodermal anomalies. Virtually all cases of NSLH are caused by an
invariant and functionally unique mutation in SHOC2 (c.4A>G, p.Ser2Gly). Here, we
report on a child with molecularly confirmed NSLH who developed a neuroblastoma,
first suspected at the age 3 months by abdominal ultrasound examination. Based on
this finding, scanning of the SHOC2 coding sequence encompassing the c.4A>G
change was performed on selected pediatric cohorts of malignancies documented to
occur in RASopathies (i.e., neuroblastoma, brain tumors, rhabdomyosarcoma, acute
lymphoblastic, and myeloid leukemia), but failed to identify a functionally
relevant cancer-associated variant. While these results do not support a major
role of somatic SHOC2 mutations in these pediatric cancers, this second instance
of neuroblastoma in NSLAH suggests a possible predisposition to this malignancy
in subjects heterozygous for the c.4A>G SHOC2 mutation.
PMID- 25846318
TI - Verification of chicken Nanog as an epiblast marker and identification of chicken
PouV as Pou5f3 by newly raised antibodies.
AB - Pluripotency is an important feature of early embryonic cells of multicellular
organisms. Recent advances in stem cell research have shown that Nanog and Pou5f1
(Oct3/4) play important roles in mammalian pluripotency. However, whether these
molecules exert conserved functions in other species remains unknown. Although
the epiblast of the early chicken embryo would provide a useful experimental
model, a lack of antibodies against chicken Nanog (cNanog) and chicken
PouV/Pou5f3 (cPouV) proteins has hampered intensive investigation. Here we report
newly raised polyclonal antibodies that specifically recognize cNanog and cPouV
proteins. The specificity and sensitivity of the antibodies were validated by
both western blotting and immunostaining with transfected 293T cells and chicken
embryonic tissues. Immunohistochemistry using these antibodies revealed that
cNanog protein was specifically localized in epiblastic cells and germ cells. In
contrast, cPouV expression was seen almost ubiquitously. We also found that
chicken epiblast-derived colony-forming cells that morphologically resemble mouse
embryonic stem cells were cNanog-positive, implying that these colony-forming
cells possess pluripotency. The anti-cPouV antibody further enabled us to
identify a previously unknown region at the N-terminus of the cPouV protein
containing a characteristic motif that is absent in mammalian Pou5f1. Thus, the
antibodies raised in this study are useful tools for studying the functions of
cNanog and cPouV at the protein level and the molecular mechanisms of chicken
pluripotency.
PMID- 25846319
TI - Gut Microbiota: The Conductor in the Orchestra of Immune-Neuroendocrine
Communication.
AB - PURPOSE: It is well established that mammals are so-called super-organisms that
coexist with a complex microbiota. Growing evidence points to the delicacy of
this host-microbe interplay and how disruptive interventions could have lifelong
consequences. The goal of this article was to provide insights into the potential
role of the gut microbiota in coordinating the immune-neuroendocrine cross-talk.
METHODS: Literature from a range of sources, including PubMed, Google Scholar,
and MEDLINE, was searched to identify recent reports regarding the impact of the
gut microbiota on the host immune and neuroendocrine systems in health and
disease. FINDINGS: The immune system and nervous system are in continuous
communication to maintain a state of homeostasis. Significant gaps in knowledge
remain regarding the effect of the gut microbiota in coordinating the immune
nervous systems dialogue. Recent evidence from experimental animal models found
that stimulation of subsets of immune cells by the gut microbiota, and the
subsequent cross-talk between the immune cells and enteric neurons, may have a
major impact on the host in health and disease. IMPLICATIONS: Data from rodent
models, as well as from a few human studies, suggest that the gut microbiota may
have a major role in coordinating the communication between the immune and
neuroendocrine systems to develop and maintain homeostasis. However, the
underlying mechanisms remain unclear. The challenge now is to fully decipher the
molecular mechanisms that link the gut microbiota, the immune system, and the
neuroendocrine system in a network of communication to eventually translate these
findings to the human situation, both in health and disease.
PMID- 25846320
TI - New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.
AB - PURPOSE: Interferon injectables and glatiramer acetate have served as the primary
disease-modifying treatments for multiple sclerosis (MS) since their introduction
in the 1990s and are first-line treatments for relapsing-remitting forms of MS
(RRMS). Many new drug therapies were launched since early 2010, expanding the
drug treatment options considerably in a disease state that once had a limited
treatment portfolio. The purpose of this review is to critically evaluate the
safety profile and efficacy data of disease-modifying agents for MS approved by
the US Food and Drug Administration (FDA) from 2010 to the present and provide
cost and available pharmacoeconomic data about each new treatment. METHODS: Peer
reviewed clinical trials, pharmacoeconomic studies, and relevant
pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000
December 2014) by using the search terms multiple sclerosis, fingolimod,
teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon,
peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics.
Citations from available articles were also reviewed for additional references.
The databases publically available at www.clinicaltrials.gov and www.fda.gov were
searched for unpublished studies or studies currently in progress. FINDINGS: A
total of 5 new agents and 1 new dosage formulation were approved by the FDA for
the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer
acetate represent 2 new effective injectable options for MS that reduce burden of
administration seen with traditional interferon and low-dose glatiramer acetate.
Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents
available for MS, and their efficacy in reducing annualized relapse rates is 48%
to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo.
Alemtuzumab is a biologic given over a 2-year span that reduced annualized
relapse rates by 55% in treatment-naive patients and by 49% in patients relapsing
on prior disease-modifying agents. Treatment emergent adverse effects were common
with all new drug treatments. The cost of treating MS remains high, because MS
therapies accounted for the highest spending growth of any specialty drug class
in 2013. Most therapies cost, on average, US $6000/mo based on wholesale
acquisition cost, and few cost-benefit studies are available for new treatments.
IMPLICATIONS: With expansion of new treatments, patients and providers now have
multiple options and improved flexibility in managing MS. The relative place in
therapy of new treatments is unknown, and treatment decisions are largely based
on patient preference, efficacy, and risk potential. The cost of treating MS
continues to be high, even with more treatment options available.
PMID- 25846321
TI - The Role of Microbiota on the Gut Immunology.
AB - PURPOSE: The human gut contains >100 trillion microbes. This microbiota plays a
crucial role in the gut homeostasis. Importantly, the microbiota contributes to
the development and regulation of the gut immune system. Dysbiosis of the gut
microbiota could also cause several intestinal and extraintestinal diseases. Many
experimental studies help us to understand the complex interplay between the host
and microbiota. METHODS: This review presents our current understanding of the
mucosal immune system and the role of gut microbiota for the development and
functionality of the mucosal immunity, with a particular focus on gut-associated
lymphoid tissues, mucosal barrier, TH17 cells, regulatory T cells, innate
lymphoid cells, dendritic cells, and IgA-producing B cells and plasma cells.
FINDINGS: Comparative studies using germ-free and conventionally-raised animals
reveal that the presence of microbiota is important for the development and
regulation of innate and adaptive immune systems. The host-microbial symbiosis
seems necessary for gut homeostasis. However, the precise mechanisms by which
microbiota contributes to development and functionality of the immune system
remain to be elucidated. IMPLICATIONS: Understanding the complex interplay
between the host and microbiota and further investigation of the host-microbiota
relationship could provide us the insight into the therapeutic and/or preventive
strategy for the disorders related to dysbiosis of the gut microbiota.
PMID- 25846322
TI - In vitro bone strain distributions in a sample of primate pelves.
AB - The pelvis is a critical link in the hindlimb locomotor system and has a central
role in resisting loads associated with locomotion, but our understanding of its
structural biomechanics is quite limited. Empirical data on how the pelvis
responds to the loads it encounters are important for understanding pelvic
adaptation to locomotion, and for testing hypotheses regarding how the pelvis is
adapted to its mechanical demands. This paper presents in vitro strain gauge data
on a sample of monkey and ape cadaveric specimens (Macaca, Papio, Ateles,
Hylobates), and assesses strain magnitudes and distributions through the bones of
the pelvis: the ilium, ischium and pubis. Pelves were individually mounted in a
materials testing system, loads were applied across three hindlimb angular
positions, and strains were recorded from 18 locations on the pelvic girdle. Peak
principal strains range from 2000 to 3000 MUepsilon, similar to peak strains
recorded from other mammals in vivo. Although previous work has suggested that
the bones of the pelvis may act as bent beams, this study suggests that there are
likely additional loading regimes superimposed on bending. Specifically, these
data suggest that the ilium is loaded in axial compression and torsion, the
ischium in torsion, the pubic rami in mediolateral bending, and the pubic
symphysis is loaded in a combination of compression and torsion. Compressive
strains dominate the pelves of all species representatives. Shear strains change
with limb position; hip flexion at 45 degrees induces smaller shear strains than
mid-stance (90 degrees ) or hip extension (105 degrees ). The pelvic girdle is a
complex structure that does not lend itself easily to modeling, but finite
element analyses may prove useful to generate and refine hypotheses of pelvic
biomechanics.
PMID- 25846323
TI - Kinematics and knee muscle activation during sit-to-stand movement in women with
knee osteoarthritis.
AB - BACKROUND: The purpose of this study was to compare joint kinematics, knee and
trunk muscle activation and co-activation patterns during a sit-to-stand movement
in women with knee osteoarthritis and age-matched controls. METHODS: Eleven women
with knee osteoarthritis (mean and standard deviation, age: 66.90, 4.51 years,
height: 1.63, 0.02 m, mass: 77.63, 5.4 kg) and eleven healthy women (mean and
standard deviation, age: 61.90, 3.12 years, height: 1.63 m, 0.03, mass: 78.30,
4.91 kg) performed a Sit to Stand movement at a self-selected slow, normal and
fast speed. Three-dimensional joint kinematics of the lower limb, vertical ground
reaction forces and electromyographic activity of the biceps femoris vastus
lateralis and erectus spinae were recorded bilaterally. FINDINGS: A two-way ANOVA
showed that the osteoarhtitis group performed the sit to stand task using a
smaller knee and hip range of motion compared with the control group while no
differences in temporal kinematics and ground reaction force-related parameters
were observed. In addition, women with osteoarhtritis displayed significantly
lower vastus lateralis coupled with a higher biceps feomoris electromyographic
activity and higher agonist-antagonist co-contraction and co-activation than
asymptomatic women. The activation of erectus spinae was not different between
groups. INTERPRETATION: Results indicate that patients with moderate knee
osteoarthritis rise from the chair using greater knee muscle co-contraction,
earlier and greater activation of the hamstrings which results in reduced hip and
knee range of motion. This may be a way to overcome the pain and potential muscle
atrophy of knee extensor muscles without compromising overall task duration.
PMID- 25846324
TI - Angular stable lateral plating is a valid alternative to conventional plate
fixation in the proximal phalanx. A biomechanical study.
AB - BACKGROUND: Dorsal plating is commonly used in proximal phalanx fractures but it
bears the risk of interfering with the extensor apparatus. In this study, dorsal
and lateral plating fixation methods are compared to assess biomechanical
differences using conventional 1.5mm non-locking plates and novel 1.3mm lateral
locking plates. METHODS: Twenty-four fresh frozen human cadaveric proximal
phalanges were equally divided into four groups. An osteotomy was set at the
proximal metaphyseal-diaphyseal junction and fixed with either dorsal (group A)
or lateral (group B) plating using a 1.5mm non-locking plate, or lateral plating
with a novel 1.3mm locking plate with bicortical (group C) or unicortical (group
D) screws. The specimens were loaded in axial, dorsovolar and mediolateral
direction to assess fixation stiffness followed by a cyclic destructive test in
dorsovolar loading direction. FINDINGS: Axial stiffness was highest in group D
(mean 321.02, SEM 21.47N/mm) with a significant difference between groups D and B
(P=0.033). Locking plates (groups C and D) were stiffer than non-locking plates
under mediolateral loading (P=0.007), no significant differences were noted under
dorsovolar loading. Furthermore, no significant differences were observed under
cyclic loading to failure between any of the study groups. INTERPRETATION: No
considerable biomechanical advantage of using a conventional 1.5mm dorsal non
locking plate was identified over the novel 1.3mm lateral locking plate in the
treatment of proximal phalanx fractures. Since the novel low-profile plate is
less disruptive to the extensor mechanism, it should be considered as a valid
alternative.
PMID- 25846325
TI - Electromyographic activity of erector spinae and external oblique muscles during
trunk lateral bending and axial rotation in patients with adolescent idiopathic
scoliosis and healthy subjects.
AB - BACKGROUND: The aim of this study was to analyze electrical activity of trunk
muscles in adolescent idiopathic scoliosis patients and healthy subjects during
trunk lateral bending and rotation movements. METHODS: Ten patients with right
thoracic scoliosis [Cobb angle: 29.1 degrees (10.4 degrees )] and 10 control
adolescents were studied. Electrical activities of erector spinae muscle at 6th
and 10th thoracic and 3rd lumbar vertebral level, and external oblique muscles
were measured bilaterally during the right and left bending from standing and
prone positions, and trunk rotation in sitting position. FINDINGS: In trunk
rotation to the right, the right-side external oblique (antagonist) muscle in
scoliosis group was greater than that in control group (p<0.05). In left bending
from standing position, in scoliosis group, the antagonistic activity of EST6
muscle was greater than its agonistic activity (p<0.05). Also, in the right
bending motion, the agonistic activity of external oblique of scoliosis group was
higher than that of control group (p=0.02). During the left bending from prone
position, right-side EST6 and right-side ESL3 muscles of scoliosis group were
greater than that of control group (p<0.05). INTERPRETATION: In left bending from
standing position, in scoliosis group, the greater antagonistic activity of
erector spinae muscle at 6th thoracic vertebral level than its agonistic
activity, indicates that scoliosis is associated with asymmetrical muscle
activity. Lateral bending from standing position is appropriate test to
distinguish between scoliosis and control subjects. In scoliosis, the
asymmetrical muscle activity is not an inherent characteristic since it was not
displayed in all back motions.
PMID- 25846326
TI - Red meat subtypes and colorectal cancer risk.
PMID- 25846327
TI - Subclinical hypothyroidism: a historical view and shifting prevalence.
AB - BACKGROUND AND AIMS: Accurate diagnosis and treatment of subclinical
hypothyroidism (SCH) is challenging in clinical practice because of differing
upper limits of normal (ULN) for thyroid-stimulating hormone (TSH). This review
summarises the various definitions of SCH and their impact on reported SCH
prevalence. METHODOLOGY: Articles reporting the prevalence of SCH in relation to
the ULN of TSH in human studies were identified through an English-language
PubMed search for 'subclinical hypothyroidism,' 'prevalence,' and 'TSH' within
the title and/or abstract. Relevant articles and related literature were selected
for inclusion. RESULTS: Estimates for the prevalence of SCH varied by sex, age,
race/ethnicity, and geographic location (range, 0.4-16.9%). Higher rates of SCH
were consistently reported in women (0.9-16.9%) and older individuals (2.7
16.9%). However, the ULN of TSH in those considered free of thyroid disease and
not at risk increased progressively with age, suggesting that reports of SCH
prevalence in elderly people may be overestimated. Multiple studies reported an
increased risk of progression to overt hypothyroidism among individuals with
elevated TSH and antithyroid antibodies. CONCLUSIONS: Given the variable
definition of SCH based on an inconsistent ULN for TSH, it is currently difficult
to ascertain the true prevalence of SCH and to correctly label and treat patients
with SCH; use of age-adjusted definitions may be considered when assessing
prevalence. A diagnosis of SCH does not necessarily merit treatment, especially
if TSH elevations are transient (i.e. not persistent for > 3-6 months) and the
patient lacks other risk factors for developing overt hypothyroidism.
PMID- 25846328
TI - In situ adaptive response to climate and habitat quality variation: spatial and
temporal variation in European badger (Meles meles) body weight.
AB - Variation in climatic and habitat conditions can affect populations through a
variety of mechanisms, and these relationships can act at different temporal and
spatial scales. Using post-mortem badger body weight records from 15 878
individuals captured across the Republic of Ireland (7224 setts across ca. 15 000
km(2) ; 2009-2012), we employed a hierarchical multilevel mixed model to evaluate
the effects of climate (rainfall and temperature) and habitat quality (landscape
suitability), while controlling for local abundance (unique badgers
caught/sett/year). Body weight was affected strongly by temperature across a
number of temporal scales (preceding month or season), with badgers being heavier
if preceding temperatures (particularly during winter/spring) were warmer than
the long-term seasonal mean. There was less support for rainfall across different
temporal scales, although badgers did exhibit heavier weights when greater
rainfall occurred one or 2 months prior to capture. Badgers were also heavier in
areas with higher landscape habitat quality, modulated by the number of
individuals captured per sett, consistent with density-dependent effects reducing
weights. Overall, the mean badger body weight of culled individuals rose during
the study period (2009-2012), more so for males than for females. With predicted
increases in temperature, and rainfall, augmented by ongoing agricultural land
conversion in this region, we project heavier individual badger body weights in
the future. Increased body weight has been associated with higher fecundity,
recruitment and survival rates in badgers, due to improved food availability and
energetic budgets. We thus predict that climate change could increase the badger
population across the Republic of Ireland. Nevertheless, we emphasize that,
locally, populations could still be vulnerable to extreme weather variability
coupled with detrimental agricultural practice, including population management.
PMID- 25846329
TI - No evidence for reduction of opioid-withdrawal symptoms by cannabis smoking
during a methadone dose taper.
AB - BACKGROUND AND OBJECTIVES: To support medication development with cannabinoids,
smoked cannabis has been said to alleviate symptoms of opioid withdrawal. We
evaluated that hypothesis. METHODS: We analyzed data from the methadone-taper
phase of a clinical trial we had conducted. Participants were 116 outpatient
heroin and cocaine users (of whom 46 were also cannabis users) who stayed for the
10-week taper. Main outcome measures were weekly urine screens for cannabinoids,
plus every-two-week assessments of opioid-withdrawal symptoms. RESULTS: Opioid
withdrawal scores did not differ overall between users and nonusers of cannabis.
In a lagged analysis in the 46 users, there was a slight (not statistically
significant) indication that weeks of higher opiate-withdrawal symptoms preceded
weeks of cannabis use (effect-size r = .20, 95% CI -.10 to .46, p = .52). Even if
this finding is taken to suggest self-medication with cannabis, a lagged analysis
in the other temporal direction showed no indication that cannabis use predicted
lower opiate-withdrawal symptoms the next week (effect-size r = .01, 95% CI -.28
to .30, p = .69). These findings persisted in sensitivity analyses controlling
for each of 17 potential confounds. DISCUSSION AND CONCLUSION: With our findings,
the clinical evidence for smoked cannabis as a reducer of opioid-withdrawal
symptoms moves slightly further from "inconclusive" or "mixed" and closer to
negative, at least in the context of a methadone dose taper like the one used
here. SCIENTIFIC SIGNIFICANCE: This finding may remove one rationale for
medication development using cannabinoids to treat opioid withdrawal, but leaves
other rationales intact.
PMID- 25846330
TI - Benchmarking of commercially available CHO cell culture media for antibody
production.
AB - In this study, eight commercially available, chemically defined Chinese hamster
ovary (CHO) cell culture media from different vendors were evaluated in batch
culture using an IgG-producing CHO DG44 cell line as a model. Medium adaptation
revealed that the occurrence of even small aggregates might be a good indicator
of cell growth performance in subsequent high cell density cultures. Batch
experiments confirmed that the culture medium has a significant impact on
bioprocess performance, but high amino acid concentrations alone were not
sufficient to ensure superior cell growth and high antibody production. However,
some key amino acids that were limiting in most media could be identified.
Unbalanced glucose and amino acids led to high cell-specific lactate and ammonium
production rates. In some media, persistently high glucose concentrations
probably induced the suppression of respiration and oxidative phosphorylation,
known as Crabtree effect, which resulted in high cell-specific glycolysis rates
along with a continuous and high lactate production. In additional experiments,
two of the eight basal media were supplemented with feeds from two different
manufacturers in six combinations, in order to understand the combined impact of
media and feeds on cell metabolism in a CHO fed-batch process. Cell growth,
nutrient consumption and metabolite production rates, antibody production, and
IgG quality were evaluated in detail. Concentrated feed supplements boosted cell
concentrations almost threefold and antibody titers up to sevenfold. Depending on
the fed-batch strategy, fourfold higher peak cell concentrations and eightfold
increased IgG titers (up to 5.8 g/L) were achieved. The glycolytic flux was
remarkably similar among the fed-batches; however, substantially different
specific lactate production rates were observed in the different media and feed
combinations. Further analysis revealed that in addition to the feed additives,
the basal medium can make a considerable contribution to the ammonium metabolism
of the cells. The glycosylation of the recombinant antibody was influenced by the
selection of basal medium and feeds. Differences of up to 50 % in the monogalacto
fucosylated (G1F) and high mannose fraction of the IgG were observed.
PMID- 25846331
TI - Concatemerization increases the inhibitory activity of short, cell-penetrating,
cationic and tryptophan-rich antifungal peptides.
AB - There are short cationic and tryptophan-rich antifungal peptides such as the
hexapeptide PAF26 (RKKWFW) that have selective toxicity and cell penetration
properties against fungal cells. This study demonstrates that concatemeric
peptides with tandem repeats of the heptapeptide PAF54 (which is an elongated
PAF26 sequence) show increased fungistatic and bacteriostatic activities while
maintaining the absence of hemolytic activity of the monomer. The increase in
antimicrobial activity of the double-repeated PAF sequences (diPAFs), compared to
the nonrepeated PAF, was higher (4-8-fold) than that seen for the triple-repeated
sequences (triPAFs) versus the diPAFs (2-fold). However, concatemerization
diminished the fungicidal activity against quiescent spores of the filamentous
fungus Penicillium digitatum. Peptide solubility and sensitivity to proteolytic
degradation were affected by the design of the concatemers: incorporation of the
AGPA sequence hinge to separate PAF54 repeats increased solubility while the C
terminal addition of the KDEL sequence decreased in vitro stability. These
results led to the design of the triPAF sequence PAF102 of 30 amino acid
residues, with increased antimicrobial activity and minimal inhibitory
concentration (MIC) value of 1-5 MUM depending on the fungus. Further
characterization of the mode-of-action of PAF102 demonstrated that it colocalizes
first with the fungal cell wall, it is thereafter internalized in an energy
dependent manner into hyphal cells of the filamentous fungus Fusarium
proliferatum, and finally kills hyphal cells intracellularly. Therefore, PAF102
showed mechanistic properties against fungi similar to the parental PAF26. These
observations are of high interest in the future development of PAF-based
antimicrobial molecules optimized for their production in biofactories.
PMID- 25846332
TI - Identification of sucrose synthase in nonphotosynthetic bacteria and
characterization of the recombinant enzymes.
AB - Sucrose synthase (SuSy) catalyzes the reversible conversion of sucrose and a
nucleoside diphosphate into fructose and nucleotide (NDP)-glucose. To date, only
SuSy's from plants and cyanobacteria, both photosynthetic organisms, have been
characterized. Here, four prokaryotic SuSy enzymes from the nonphotosynthetic
organisms Nitrosomonas Europaea (SuSyNe), Acidithiobacillus caldus (SuSyAc),
Denitrovibrio acetiphilus (SusyDa), and Melioribacter roseus (SuSyMr) were
recombinantly expressed in Escherichia coli and thoroughly characterized. The
purified enzymes were found to display high-temperature optima (up to 80 degrees
C), high activities (up to 125 U/mg), and high thermostability (up to 15 min at
60 degrees C). Furthermore, SuSyAc, SuSyNe, and SuSyDa showed a clear preference
for ADP as nucleotide, as opposed to plant SuSy's which prefer UDP. A structural
and mutational analysis was performed to elucidate the difference in NDP
preference between eukaryotic and prokaryotic SuSy's. Finally, the physiological
relevance of this enzyme specificity is discussed in the context of metabolic
pathways and genomic organization.
PMID- 25846333
TI - Outer membrane proteins related to SusC and SusD are not required for Cytophaga
hutchinsonii cellulose utilization.
AB - Cytophaga hutchinsonii, a member of the phylum Bacteroidetes, employs a novel
collection of cell-associated proteins to digest crystalline cellulose. Other
Bacteroidetes rely on cell surface proteins related to the starch utilization
system (Sus) proteins SusC and SusD to bind oligosaccharides and import them
across the outer membrane for further digestion. These bacteria typically produce
dozens of SusC-like porins and SusD-like oligosaccharide-binding proteins to
facilitate utilization of diverse polysaccharides. C. hutchinsonii specializes in
cellulose digestion and its genome has only two susC-like genes and two susD-like
genes. Single and multiple gene deletions were constructed to determine if the
susC-like and susD-like genes have roles in cellulose utilization. A mutant
lacking all susC-like and all susD-like genes digested cellulose and grew on
cellulose as well as wild-type cells. Further, recombinantly expressed SusD-like
proteins CHU_0547 and CHU_0554 failed to bind cellulose or beta-glucan
hemicellulosic polysaccharides. The results suggest that the Bacteroidetes Sus
paradigm for polysaccharide utilization may not apply to the cellulolytic
bacterium C. hutchinsonii.
PMID- 25846334
TI - Engineering the heterologous expression of lanthipeptides in Escherichia coli by
multigene assembly.
AB - Lantibiotics are an important class of ribosomally synthesised peptide
antibiotics with a remarkable pharmacological potential. Structural variants of
lantibiotics generated by peptide engineering in vivo are an important aspect for
improving the peptide's efficacy, stability and bioavailability as well as
production titre, which severely impacts the potential exploitation in
pharmaceutical applications. Therefore, expression systems are needed which allow
for a robust genetic access for ample mutagenesis experiments. Based on previous
heterologous expression of the two-component lanthipeptide lichenicidin (Blialpha
and Blibeta) in Escherichia coli BLic5, we now employ a multigene assembly
strategy for recombinant lantibiotic peptide production in the Gram-negative
host. Two E. coli high copy plasmids for separate and increased expression of a
two-component lantibiotic were cloned and tested for expression. From these E.
coli HP expression strains, an up to 100 times increased expression was found
compared with Bacillus licheniformis I89 and E. coli BLic5. Total expression
yields reach 4 mg L(-1) for Blialpha and 6 mg L(-1) for Blibeta. The expression
system developed in this study constitutes an important cornerstone for future in
vivo peptide engineering studies and is of significance for potential
applications aiming at higher production titres of ribosomally synthesised, post
translationally modified peptides.
PMID- 25846335
TI - Physiologo-biochemical characteristics of citrate-producing yeast Yarrowia
lipolytica grown on glycerol-containing waste of biodiesel industry.
AB - In this study, physiologo-biochemical characteristics of citrate-producing yeast
Yarrowia lipolytica grown on glycerol-containing waste of biodiesel industry were
studied by an investigation of growth dynamics, the consumption of glycerol, and
the fatty acid fractions from waste as well as by measuring the activities of
enzymes involved in the metabolism of waste. It was shown that Y. lipolytica
realizes concurrent uptake of glycerol and the fatty acid fractions during
conversion of glycerol-containing waste, although glycerol was utilized at a
higher rate than fatty acids. Under optimal feeding of glycerol-containing waste
by portions of 20 g l(-1), the citric acid production and the ratio between
citric acid and isocitric acid depended on the strain used. It was revealed that
wild strain Y. lipolytica VKM Y-2373 produced citrate and isocitrate with a ratio
of 1.7:1, while the mutant strain Y. lipolytica NG40/UV7 synthesized presumably
citric acid (122.2 g l(-1)) with a citrate-to-isocitrate ratio of 53:1 and the
yield of 0.95 g g(-1).
PMID- 25846336
TI - Comparative study of MnO2 nanoparticle synthesis by marine bacterium
Saccharophagus degradans and yeast Saccharomyces cerevisiae.
AB - Microorganisms are one of the most attractive and simple sources for the
synthesis of different types of metal nanoparticles. The synthesis of manganese
dioxide nanoparticles (MnO2 NPs) by microorganisms from reducing potassium
permanganate was investigated for the first time in the present study. The
microbial supernatants of the bacterium Saccharophagus degradans ATCC 43961 (Sde
2-40) and of the yeast Saccharomyces cerevisiae showed positive reactions to the
synthesis of MnO2 NPs by displaying a change of color in the permanganate
solution from purple to yellow. KMnO4-specific peaks also disappeared and MnO2
specific peaks emerged at an absorption maximum of 365 nm in UV-visible
spectrophotometry. The washed Sde 2-40 cells did not show any ability to
synthesize MnO2 NPs. The medium and medium constituents of Sde 2-40 showed
similar positive reactions as supernatants, which indicate the role of the Sde 2
40 medium constituents in the synthesis of MnO2 NPs. This suggests that
microorganisms without nanoparticle synthesis ability can be misreported for
their abilities to synthesize nanoparticles. S. cerevisiae washed cells showed an
ability to synthesize MnO2 NPs. The strategies of keeping yeast cells in tea bags
and dialysis membranes showed positive tests for the synthesis of MnO2 NPs. A
Fourier transform-infrared spectroscopy study suggested roles for the proteins,
alcoholic compounds, and cell walls of S. cerevisiae cells in the synthesis of
MnO2 NPs. Electron-dispersive X-ray spectroscopy analyses confirmed the presence
of Mn and O in the sample. X-ray photoelectron spectroscopy revealed
characteristic binding energies for MnO2 NPs. Transmission electron microscopy
micrographs revealed the presence of uniformly dispersed hexagonal- and spherical
shaped particles with an average size of 34.4 nm. The synthesis approach using
yeast is possible by a simple reaction at low temperature without any need for
catalysts, templates, or expensive and precise equipment. Therefore, this study
will be useful for the easy, cost-effective, reliable, and eco-friendly
production of nanomaterials.
PMID- 25846337
TI - Saccharomyces cerevisiae EC-1118 enhances the survivability of probiotic
Lactobacillus rhamnosus HN001 in an acidic environment.
AB - The present study attempted to partially characterize and elucidate the viability
enhancing effect of a yeast strain Saccharomyces cerevisiae EC-1118 on a
probiotic strain Lactobacillus rhamnosus HN001 under acidic conditions using a
model system (non-growing cells). The yeast was found to significantly enhance (P
< 0.05) the viability of the probiotic strain under acidic conditions (pH 2.5 to
4.0) by 2 to 4 log cycles, and the viability-enhancing effects were observed to
be influenced by pH, and probiotic and yeast concentrations. Microscopic
observation and co-aggregation assay revealed that the viability-enhancing effect
of the yeast could be attributed to direct cell-cell contact co-aggregation
mediated by yeast cell surface and/or cell wall components or metabolites.
Furthermore, non-viable yeast cells killed by thermal means were observed to
enhance the viability of the probiotic strain as well, suggesting that the
surface and/or cell wall component(s) of the yeast contributing to co-aggregation
was heat-stable. Cell-free yeast supernatant was also found to enhance the
viability of the probiotic strain, indicating the presence of protective yeast
metabolite(s) in the supernatant. These findings laid the foundation for further
understanding of the mechanism(s) involved and for developing novel microbial
starter cultures possibly without the use of live yeast for ambient-stable high
moisture probiotic foods.
PMID- 25846338
TI - Erratum to: mismatch discrimination in fluorescent in situ hybridization using
different types of nucleic acids.
PMID- 25846339
TI - Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming
induced transendothelial migration of human eosinophils.
AB - BACKGROUND: Priming with cytokines such as granulocyte-macrophage colony
stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the
excessive accumulation of eosinophils within the bronchial mucosa of asthmatics.
However, mechanisms that drive GM-CSF priming are incompletely understood. Notch
signaling is an evolutionarily conserved pathway that regulates cellular
processes, including migration, by integrating exogenous and cell-intrinsic cues.
This study investigates the hypothesis that the priming-induced enhanced
migration of human eosinophils requires the Notch signaling pathway. METHODS:
Using pan Notch inhibitors and newly developed human antibodies that specifically
neutralize Notch receptor 1 activation, we investigated a role for Notch
signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and
in the airway accumulation of mouse eosinophils in vivo. RESULTS: Notch receptor
1 was constitutively active in freshly isolated human blood eosinophils, and
inhibition of Notch signaling or specific blockade of Notch receptor 1 activation
during GM-CSF priming impaired priming-enhanced eosinophil transendothelial
migration in vitro. Inclusion of Notch signaling inhibitors during priming was
associated with diminished ERK phosphorylation, and ERK-MAPK activation was
required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil
accumulation within allergic airways was impaired following systemic treatment
with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with
Notch inhibitor. CONCLUSIONS: These data identify Notch signaling as an intrinsic
pathway central to GM-CSF priming-induced eosinophil tissue migration.
PMID- 25846341
TI - Erratum to: The Effects of Nandrolone Decanoate Along with Prolonged Low
Intensity Exercise on Susceptibility to Ventricular Arrhythmias.
PMID- 25846340
TI - Faster-acting insulin aspart: earlier onset of appearance and greater early
pharmacokinetic and pharmacodynamic effects than insulin aspart.
AB - AIMS: To evaluate the pharmacokinetics and pharmacodynamics of faster-acting
insulin aspart and insulin aspart in a randomized, single-centre, double-blind
study. METHODS: Fifty-two patients with type 1 diabetes (mean age 40.3 years)
received faster-acting insulin aspart, insulin aspart, or another faster aspart
formulation (not selected for further development), each as a single 0.2 U/kg
subcutaneous dose, under glucose-clamp conditions, in a three-way crossover
design (3-12 days washout between dosing). RESULTS: Faster-acting insulin aspart
had a faster onset of exposure compared with insulin aspart, shown by a 57%
earlier onset of appearance [4.9 vs 11.2 min; ratio 0.43, 95% confidence interval
(CI) 0.36; 0.51], a 35% earlier time to reach 50% maximum concentration (20.7 vs
31.6 min; ratio 0.65, 95% CI 0.59; 0.72) and a greater early exposure within 90
min after dosing. The greatest difference occurred during the first 15 min, when
area under the serum insulin aspart curve was 4.5-fold greater with faster-acting
insulin aspart than with insulin aspart. Both treatments had a similar time to
maximum concentration, total exposure and maximum concentration. Faster-acting
insulin aspart had a significantly greater glucose-lowering effect within 90 min
after dosing [largest difference: area under the curve for the glucose infusion
rate (AUC(GIR), 0-30 min) ratio 1.48, 95% CI 1.13; 2.02] and 17% earlier time to
reach 50% maximum glucose infusion rate (38.3 vs 46.1 min; ratio 0.83, 95% CI
0.73; 0.94). The primary endpoint (AUC(GIR, 0-2 h)) was 10% greater for faster
acting insulin aspart, but did not reach statistical significance (ratio 1.10,
95% CI 1.00; 1.22). Both treatments had similar total and maximum glucose
lowering effects, indicating similar overall potency. CONCLUSIONS: Faster-acting
insulin aspart was found to have earlier onset and higher early exposure than
insulin aspart, and a greater early glucose-lowering effect, with similar
potency.
PMID- 25846342
TI - Protective Effect of Hydroxytyrosol Against Cardiac Remodeling After
Isoproterenol-Induced Myocardial Infarction in Rat.
AB - The present study aimed to investigate the cardioprotective effect of
hydroxytyrosol (HT) against isoproterenol-induced myocardial infarction in rats.
Male rats were randomly divided into four groups, control, isoproterenol (Isop)
and pretreated animals with HT in two different doses (2 and 5 mg/kg) orally for
7 days and intoxicated with isoproterenol (Isop + HT1) and (Isop + HT2) groups.
Myocardial infarction in rats was induced subcutaneously by isoproterenol (100
mg/kg, s.c.) at an interval of 24 h on 6th and 7th day. On 8th day,
electrocardiographic (ECG) pattern, gravimetric and biochemical parameters were
assessed. Isoproterenol exhibited changes in ECG pattern, including significant
ST-segment elevation and increase in the serum troponin-T level by 317 % as
compared to control rats. Moreover, cardiac injury markers (creatine kinase-MB,
lactate dehydrogenase, alanine aminotransferase) underwent a notable rise in
serum of infarcted animals. Else, a disturbance in lipids profile and significant
increase in lipase and angiotensin-converting enzyme (ACE) activities and heart
weight ratio were observed in isoproterenol group. However, pre- and co-treatment
with HT (2 and 5 mg/kg) improved the myocardium injury, restored the hemodynamic
function and inhibited the ACE activity that prevent cardiac hypertrophy and
remodeling. Overall, these findings demonstrated that HT exerted a potent
cardioprotective effect against isoproterenol-induced myocardial infarction.
PMID- 25846343
TI - Reversal of warfarin anticoagulation for urgent surgical procedures.
AB - PURPOSE: Patients treated with warfarin for therapeutic anticoagulation present a
challenge for the perioperative management of urgent and emergent surgery.
Anticoagulation must be reversed prior to most surgical procedures to prevent
intraoperative bleeding. The purpose of this module is to review the options for
urgent reversal of warfarin anticoagulation and the indications for each reversal
agent. Selection of the appropriate agent is important to reduce unnecessary
complications of treatment and to achieve optimal reversal of anticoagulation.
PRINCIPAL FINDINGS: When urgent surgery is required for patients taking warfarin,
intravenous vitamin K1 should be used for procedures that can be delayed for six
to 12 hr. Vitamin K1 results in the activation of existing clotting factors
rather than requiring the synthesis of new proteins, which allows for its
relatively rapid onset of action. Intravenous vitamin K1 acts more quickly than
oral administration, with reversal of anticoagulation occurring within six to 12
hr vs 18-24 hr, respectively. If surgery cannot be delayed, prothrombin complex
concentrates (PCCs) should be given, and intravenous vitamin K1 should be infused
concurrently to ensure sustained reversal of anticoagulation. The duration of
action of both PCCs and plasma is six hours due to the short half-life of factor
VII. Prothrombin complex concentrates contain small amounts of heparin and are
contraindicated in patients with heparin-induced thrombocytopenia. Plasma should
be used only if PCCs are unavailable or are contraindicated. CONCLUSION: Reversal
of warfarin anticoagulation can be achieved in a safe and timely manner when the
appropriate agent is selected and administered correctly.
PMID- 25846344
TI - Celecoxib pharmacogenetics and pediatric adenotonsillectomy: a double-blinded
randomized controlled study.
AB - BACKGROUND: Pediatric adenotonsillectomy (A&T) is associated with prolonged pain
and functional limitation. Celecoxib is an effective analgesic in adult surgery
patients; however, its analgesic efficacy on pain and functional recovery in
pediatric A&T patients is unknown. METHODS: During 2009-2012, children (age 2-18
yr) scheduled for elective A&T were enrolled in a single-centre double-blind
randomized controlled trial. Study participants received either oral placebo or
celecoxib 6 mg.kg(-1) preoperatively, followed by 3 mg.kg(-1) twice daily for
five doses. The primary outcome was the mean "worst 24-hr pain" scores during
postoperative days (PODs) 0-2 on a 100-mm visual analogue scale (VAS). Secondary
outcomes for PODs 0-7 included co-analgesic consumption, adverse events, and
functional recovery. The impact of the CYP2C9*3 allele - associated with reduced
celecoxib hepatic metabolism - on recovery was considered. RESULTS: Of the 282
children enrolled, 195 (celecoxib = 101, placebo = 94) were included in the
primary outcome analysis. While on treatment, children receiving celecoxib
experienced a modest reduction in the average pain experienced over PODs 0-2 (7
mm on a VAS; 95% confidence interval [CI]: 0.3 to 14; P = 0.04) and a "clinically
significant" reduction (>= 10 mm on a VAS; P <= 0.01) on PODs 0 and 1. During
PODs 0-2, the mean acetaminophen consumption was lower in the celecoxib group vs
the placebo group (78 mg.kg(-1); 95% CI: 68 to 89 vs 97 mg.kg(-1); 95% CI: 85 to
109, respectively; P = 0.03). No differences in adverse events, functional
recovery, or satisfaction were observed by POD 7. The CYP2C9*3 allele was
associated with less pain and improved functional recovery. CONCLUSIONS: A three
day course of oral celecoxib reduces early pain and co-analgesic consumption;
however, an increase in dose, dose frequency, and duration of dose may be
required for sustained pain relief in the pediatric setting. The CYP2C9*3 allele
may influence recovery. This trial was registered at: ClinicalTrials.gov:
NCT00849966.
PMID- 25846345
TI - Functional brain development in growth-restricted and constitutionally small
fetuses: a fetal magnetoencephalography case-control study.
AB - OBJECTIVE: Fetal magnetoencephalography records fetal brain activity non
invasively. Delayed brain responses were reported for fetuses weighing below the
tenth percentile. To investigate whether this delay indicates delayed brain
maturation resulting from placental insufficiency, this study distinguished two
groups of fetuses below the tenth percentile: growth-restricted fetuses with
abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for
gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were
compared with fetuses of adequate weight for gestational age (AGA), matched for
age and behavioural state. DESIGN: A case-control study of matched pairs.
SETTING: Fetal magnetoencephalography-Center at the University Hospital of
Tuebingen. POPULATION: Fourteen IUGR fetuses and 23 SGA fetuses were matched for
gestational age and fetal behavioural state with 37 healthy, normal-sized
fetuses. METHODS: A 156-channel fetal magentoencephalography system was used to
record fetal brain activity. Light flashes as visual stimulation were applied to
the fetus. The Student's t-test for paired groups was performed. MAIN OUTCOME
MEASURE: Latency of fetal visual evoked magnetic responses (VER). RESULTS: The
IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms;
controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies
compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828).
Behavioural states were similarly distributed. CONCLUSION: Visual evoked
responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as
an influencing factor of brain response latency was accounted for in the
comparison. This reinforces that delayed brain maturation is the result of
placental insufficiency.
PMID- 25846346
TI - Characterization of two novel HLA-A null alleles: A*11:210N and A*26:107N.
AB - Two new HLA-A null alleles were characterized, A*11:210N and A*26:107N.
PMID- 25846347
TI - Effect of visco-elastic silk-chitosan microcomposite scaffolds on matrix
deposition and biomechanical functionality for cartilage tissue engineering.
AB - Commonly used polymer-based scaffolds often lack visco-elastic properties to
serve as a replacement for cartilage tissue. This study explores the effect of
reinforcement of silk matrix with chitosan microparticles to create a visco
elastic matrix that could support the redifferentiation of expanded chondrocytes.
Goat chondrocytes produced collagen type II and glycosaminoglycan (GAG)-enriched
matrix on all the scaffolds (silk:chitosan 1:1, 1:2 and 2:1). The control group
of silk-only constructs suffered from leaching out of GAG molecules into the
medium. Chitosan-reinforced scaffolds retained a statistically significant (p <
0.02) higher amount of GAG, which in turn significantly increased (p < 0.005) the
aggregate modulus (as compared to silk-only controls) of the construct akin to
that of native tissue. Furthermore, the microcomposite constructs demonstrated
highly pronounced hysteresis at 4% strain up to 400 cycles, mimicking the visco
elastic properties of native cartilage tissue. These results demonstrated a step
towards optimizing the design of biomaterial scaffolds used for cartilage tissue
engineering. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 25846348
TI - Isolated shoulder weakness as a result of a cortical infarction in the precentral
gyrus.
AB - Since its discovery, our understanding of the primary motor cortex has continued
to evolve. The presentations of rare, isolated, motor palsies of small muscle
groups have heavily contributed to the characterization of the somatotopic
representation of the human body on the cortex. We present a case of localized,
left shoulder small muscle group weakness secondary to ischemic cerebral
infarction in the primary motor cortex. The patient experienced full recovery
over several days. Strokes causing isolated shoulder weakness are rare due to the
relatively small area dedicated to shoulder motor function in the precentral
gyrus. However, our patient presented with a larger area of infarction than in
previously reported cases, demonstrating the large individual variability that
may exist within the motor cortex somatotopic map.
PMID- 25846349
TI - TRACER: an 'eye-opener' to the patient experience across the transition of care
in an internal medicine resident program.
AB - BACKGROUND: A safe patient transition requires a complex set of physician skills
within the interprofessional practice. OBJECTIVE: To evaluate a rotation which
applies self-reflection and workplace learning in a TRAnsition of CarE Rotation
(TRACER) for internal medicine (IM) residents. TRACER is a 2-week required IM
resident rotation where trainees join a ward team as a quality officer and follow
patients into postacute care. METHODS: In 2010, residents participated in
semistructured, one-on-one interviews as part of ongoing program evaluation. They
were asked what they had learned on TRACER, the year prior, and how they used
those skills in their practice. Using transcripts, the authors reviewed and coded
each transcript to develop themes. RESULTS: Five themes emerged from a
qualitative, grounded theory analysis: seeing things from the other side, the 'ah
ha' moment of fragmented care, team collaboration including understanding nursing
scope of practice in different settings, patient understanding, and passing the
learning on. TRACER gives residents a moment to breathe and open their eyes to
the interprofessional practice setting and the patient's experience of care in
transition. CONCLUSIONS: Residents learn about transitions of care through self
reflection. This learning is sustained over time and is valued enough to teach to
their junior colleagues.
PMID- 25846350
TI - A profile of Latinos with poorly controlled diabetes in South Florida.
AB - INTRODUCTION: Latinos are the largest minority group in the United States and
diabetes or pre-diabetes affects more than 70% of Latinos aged 45 years and
older. Miami-Dade County is home to one of the highest populations of diverse
Latinos. In this descriptive manuscript, we present baseline characteristics of
participants enrolled in the Miami Healthy Heart Initiative (MHHI). This was a
study conducted to determine the effects of a community health worker (CHW)
intervention among Latinos with poorly controlled diabetes in South Florida.
METHODS: We recruited 300 diverse Latino adults with suboptimal diabetes outcomes
(HbA1c>=8) into MHHI. This randomized control trial examined the impact of a 1
year CHW-led intervention on glycemic control, blood pressure, and cholesterol
levels. At baseline, physiologic measures, including HbA1c, LDL, blood pressure,
and BMI, were assessed. Data on socio-demographic characteristics and additional
determinants of health such as depression status, provider communication, diet,
exercise, cigarette smoking, readiness to change diabetes management behaviors
(stages of change), and confidence in ability to improve diabetes self-care (self
efficacy) were collected. RESULTS: Participants came from 20 different countries,
with Cuban Americans representing 38% of the sample. Most had lived in the US for
more than 10 years, had completed at least 12 years of school, and had high
levels of health literacy, yet 48% had very low acculturation. Nearly 80% had
poor self-efficacy, 80% met the criteria for depression, and 83% were not
adherent to their medications. More than half the population was not at their
target for blood pressure, 50% were above the recommended LDL goal, and most were
obese. CONCLUSION: In a diverse population of Latinos with poorly controlled
diabetes in Miami, we found high rates of depression, obesity, medication non
adherence, poor self-efficacy, and provider communication. These may contribute
to poor diabetes control, high blood pressure, and elevated cholesterol.
PMID- 25846351
TI - A case of acute generalized exanthematous pustulosis associated with
polyarteritis nodosa, responding to systemic steroids.
AB - A patient with a known biopsy of polyarteritis nodosa diagnosis presented with
cyclic fevers, acute kidney injury, and progression of rash from macular to
pustular, worsening despite being on antibiotics, without evidence of infection
on multiple cultures. The patient had a pathological diagnosis from a skin biopsy
of acute generalized exanthematous pustulosis syndrome, with a total resolution
of rash, fevers, and acute kidney injury on treatment with pulse steroids.
PMID- 25846352
TI - Acquired tracheoesophageal fistula status post laryngeal neoplasm resection.
AB - A tracheoesophageal fistula (TEF), albeit rare, can be a life-threatening
condition that requires prompt identification and treatment. Pulmonary
contamination and restriction of proper nutrition are common, unfortunate
consequences of untreated TEFs and are often the causes of mortality in this
population. In our patient, a history of laryngeal malignancy along with symptoms
of chest pain and cough with ingestion of liquids, even without evidence of
aspiration pneumonia, appropriately prompted investigation for potential TEF.
Initial imaging through barium swallow identified the TEF, and the patient
underwent treatment with endoclips by endoscopy with bronchoscopic assistance.
PMID- 25846353
TI - Modified Early Warning System improves patient safety and clinical outcomes in an
academic community hospital.
AB - BACKGROUND AND OBJECTIVE: Severe adverse events such as cardiac arrest and death
are often heralded by abnormal vital signs hours before the event. This
necessitates an organized track and trigger approach of early recognition and
response to subtle changes in a patient's condition. The Modified Early Warning
System (MEWS) is one of such systems that use temperature, blood pressure, pulse,
respiratory rate, and level of consciousness with each progressive higher score
triggering an action. Root cause analysis for mortalities in our institute has
led to the implementation of MEWS in an effort to improve patient outcomes. Here
we discuss our experience and the impact of MEWS implementation on patient care
at our community academic hospital. METHODS: MEWS was implemented in a
protocolized manner in June 2013. The following data were collected from non-ICU
wards on a monthly basis from January 2010 to June 2014: 1) number of rapid
response teams (RRTs) per 100 patient-days (100PD); 2) number of cardiopulmonary
arrests 'Code Blue' per 100PD; and 3) result of each RRT and Code Blue (RRT
progressed to Code Blue, higher level of care, ICU transfer, etc.). Overall
inpatient mortality data were also analyzed. RESULTS: Since the implementation of
MEWS, the number of RRT has increased from 0.24 per 100PD in 2011 to 0.38 per
100PD in 2013, and 0.48 per 100PD in 2014. The percentage of RRTs that progressed
to Code Blue, an indicator of poor outcome of RRT, has been decreasing. In
contrast, the numbers of Code Blue in non-ICU floors has been progressively
decreasing from 0.05 per 100PD in 2011 to 0.02 per 100PD in 2013 and 2014. These
improved clinical outcomes are associated with a decline of overall inpatient
mortality rate from 2.3% in 2011 to 1.5% in 2013 and 1.2% in 2014. CONCLUSIONS:
Implementation of MEWS in our institute has led to higher rapid response system
utilization but lower cardiopulmonary arrest events; this is associated with a
lower mortality rate, and improved patient safety and clinical outcomes. We
recommend the widespread use of MEWS to improve patient outcomes.
PMID- 25846354
TI - Owning our off-ramps.
AB - In this issue of JCHIMP, Meade et al., publish the results of qualitative
analysis regarding a second-year rotation in tracing the outcome of discharged
patients. They report that their residents develop remarkable insights into the
types of failures and miscommunications that plague our discharge processes. This
perspective piece places this article in the context of literature seeking to
understand why these problems are endemic and how we must prioritize efforts to
address and prevent them.
PMID- 25846355
TI - Frank's sign: a potential predictor of cardiovascular disease.
PMID- 25846356
TI - The Val142Ile transthyretin cardiac amyloidosis: more than an Afro-American
pathogenic variant.
PMID- 25846357
TI - Response to letter.
PMID- 25846358
TI - Initial evaluation of thyroid nodules by primary care physicians and internal
medicine residents.
AB - OBJECTIVE: The article studied the knowledge and practice patterns of primary
care providers and internal medicine residents in their initial evaluation of
thyroid nodules and determined whether their practice is in accordance with
published guidelines by the American Thyroid Association and American Association
of Clinical Endocrinologists. METHOD: A survey was distributed to primary care
physicians (PCPs) and internal medicine residents at a community hospital in
Baltimore and a chart review was conducted at the Diabetes and Endocrine Center
in the same hospital. RESULTS: A total of 47 physicians (70%) responded to the
survey, 16 PCPs and 33 residents. Most responders (96%) will always obtain a TSH,
and of these, 21% of PCP and 25% of residents will obtain a TSH without any other
laboratory work-up. Fifty percent of the physicians (PCP, 75%; resident, 39%)
will always obtain a thyroid ultrasound (p=0.043). Most physicians (97%) will
refer for a fine-needle aspiration (FNA) biopsy of a nodule >1 cm. Sixty-two
percent of the physicians will not put a euthyroid patient on levothyroxine
suppression therapy. Many physicians (48%) are not aware of the AACE and ATA
thyroid nodule guidelines. Most physicians (65%) have not read the guidelines. Of
the 113 charts reviewed, TSH was obtained alone in 40% and with other laboratory
tests in 74%. Thyroid ultrasound was done in 67%. Only one patient was on
levothyroxine for levothyroxine suppression therapy. DISCUSSION: Although many
physicians were not aware of the guidelines, and a small number of physicians
have read them, many PCP and residents responded in concordance with the
guidelines in obtaining TSH, an ultrasound, performing FNA biopsy, and not
providing levothyroxine suppressive therapy in euthyroid patients. No differences
were found between the responses of PCP and residents except for obtaining an
ultrasound. Chart review data also showed that majority of tests ordered for non
toxic thyroid nodule evaluation were in agreement with the guidelines.
Limitations include low survey response rate among PCPs and that results are from
one community hospital. CONCLUSION: Our findings from the survey and chart review
conclude that majority of primary care physicians were initiating the appropriate
work up of thyroid nodules prior to referral to a specialist.
PMID- 25846359
TI - Editor's notes.
PMID- 25846360
TI - Respirator Testing Using Virus Aerosol: Comparison between Viability Penetration
and Physical Penetration.
AB - Viability, fluorescence (particle volume), photometric, viral RNA, and particle
number penetration of MS2 bacteriophage through filter media used in three
different models of respirators were compared to better understand the
correlation between viability and physical penetration. Although viability and
viral RNA penetration were better represented by particle volume penetration than
particle number penetration, they were several-fold lower than photometric
penetration, which was partially due to the difference in virus survival between
upstream and downstream aerosol samples. Results suggest that the current NIOSH
photometer-based test method can be used as a quick means to roughly
differentiate respirators with different performance against virus aerosols.
PMID- 25846361
TI - Demographic and Occupational Differences Between Ethnic Minority Workers Who Did
and Did Not Complete the Telephone Survey in English.
AB - BACKGROUND/OBJECTIVES: Limited research indicates that using English language
only surveys in prevalence studies conducted in the general population or in
specific ethnic populations may result in unrepresentative samples and biased
results. In this study, we investigated whether participants from ethnic
minorities who chose to answer a study interview in a language other than English
(LOTE) differed from those who completed the interview in English. METHODS: This
study was conducted within an Australian population-based telephone survey that
assessed the prevalence of occupational exposure to carcinogens among 749 ethnic
minority workers. We used modified Poisson regression to determine the factors
associated with completing the interview in a LOTE. RESULTS: Participants who
elected to complete the interview in a LOTE differed from those who completed it
in English on several factors, including sex, country of birth, education,
occupation, and occupational exposure to carcinogens (40% compared with 29%, P <
0.01). CONCLUSIONS: The participants who chose to complete the study interview in
their native language had several demographic differences from those participants
who completed it in English, and were more likely to be exposed to carcinogens at
work. Prevalence studies that offer only English language study instruments are
unlikely to produce representative samples of minority groups, and may therefore
produce biased results.
PMID- 25846362
TI - Occupational Exposure to Nano-Objects and Their Agglomerates and Aggregates
Across Various Life Cycle Stages; A Broad-Scale Exposure Study.
AB - BACKGROUND: Occupational exposure to manufactured nano-objects and their
agglomerates, and aggregates (NOAA) has been described in several workplace air
monitoring studies. However, data pooling for general conclusions and exposure
estimates are hampered by limited exposure data across the occupational life
cycle of NOAA and a lack in comparability between the methods of collecting and
analysing the data. By applying a consistent method of collecting and analysing
the workplace exposure data, this study aimed to provide information about the
occupational NOAA exposure levels across various life cycle stages of NOAA in the
Netherlands which can also be used for multi-purpose use. METHODS: Personal/near
field task-based exposure data was collected using a multi-source exposure
assessment method collecting real time particle number concentration, particle
size distribution (PSD), filter-based samples for morphological, and elemental
analysis and detailed contextual information. A decision logic was followed
allowing a consistent and objective way of analysing the exposure data. RESULTS:
In total, 46 measurement surveys were conducted at 15 companies covering 18
different exposure situations across various occupational life cycle stages of
NOAA. Highest activity-effect levels were found during replacement of big bags
(<1000-76000 # cm(-3)), mixing/dumping of powders manually (<1000-52000 # cm(-3))
and mechanically (<1000-100000 # cm(-3)), and spraying of liquid (2000-800000 #
cm(-3)) showing a high variability between and within the various exposure
situations. In general, a limited change in PSD was found during the activity
compared to the background. CONCLUSIONS: This broad-scale exposure study gives a
comprehensive overview of the NOAA exposure situations in the Netherlands and an
indication of the levels of occupational exposure to NOAA across various life
cycle of NOAA. The collected workplace exposure data and contextual information
will serve as basis for future pooling of data and modelling of worker exposure.
PMID- 25846363
TI - Oxidative Potential of Particles in Different Occupational Environments: A Pilot
Study.
AB - The oxidative potential (OP) of particulate matter has been proposed as a
toxicologically relevant metric. This concept is already frequently used for
hazard characterization of ambient particles but it is still seldom applied in
the occupational field. The objective of this study was to assess the OP in two
different types of workplaces and to investigate the relationship between the OP
and the physicochemical characteristics of the collected particles. At a toll
station, at the entrance of a tunnel ('Tunnel' site), and at three different
mechanical yards ('Depot' sites), we assessed particle mass (PM4 and PM2.5 and
size distribution), number and surface area, organic and elemental carbon,
polycyclic aromatic hydrocarbon (PAH), and four quinones as well as iron and
copper concentration. The OP was determined directly on filters without
extraction by using the dithiothreitol assay (DTT assay-OP(DTT)). The averaged
mass concentration of respirable particles (PM4) at the Tunnel site was about
twice the one at the Depot sites (173+/-103 and 90+/-36 ug m(-3), respectively),
whereas the OP(DTT) was practically identical for all the sites (10.6+/-7.2 pmol
DTT min(-1) MUg(-1) at the Tunnel site; 10.4+/-4.6 pmol DTT min(-1) MUg(-1) at
the Depot sites). The OP(DTT) of PM4 was mostly present on the smallest PM2.5
fraction (OP(DTT) PM2.5: 10.2+/-8.1 pmol DTT min(-1) MUg(-1); OP(DTT) PM4: 10.5+/
5.8 pmol DTT min(-1) MUg(-1) for all sites), suggesting the presence of redox
inactive components in the PM2.5-4 fraction. Although the reactivity was similar
at the Tunnel and Depot sites irrespective of the metric chosen (OP(DTT) ug(-1)
or OP(DTT) m(-3)), the chemicals associated with OP(DTT) were different between
the two types of workplaces. The organic carbon, quinones, and/or metal content
(Fe, Cu) were strongly associated with the DTT reactivity at the Tunnel site
whereas only Fe and PAH were associated (positively and negatively, respectively)
with this reactivity at the Depot sites. These results demonstrate the
feasibility of measuring of the OP(DTT) in occupational environments and suggest
that the particulate OP(DTT) is integrative of different physicochemical
properties. This parameter could be a potentially useful exposure proxy for
investigating particle exposure-related oxidative stress and its consequences.
Further research is needed mostly to demonstrate the association of OP(DTT) with
relevant oxidative endpoints in humans exposed to particles.
PMID- 25846364
TI - Pronamide: Human relevance of liver-mediated rat leydig cell tumors.
AB - Dietary exposure to pronamide resulted in higher incidences of Leydig cell tumors
(LCT) at 1000ppm in a 2-year cancer bioassay, but there were no testes effects at
40 or 200ppm, and no testes effects at 12-months at any concentration. A 90-day
mode-of-action (MoA) study was conducted at concentrations of 0, 200, 1000 and
2000ppm. Standard parameters and stereological and proliferation analyses of LCs,
targeted testis and liver gene expression, in vitro metabolism of testosterone by
liver microsomes, and quantification of serum hormones and testosterone
metabolites were evaluated. Increased testosterone metabolism due to increases in
hepatic microsomal activity, alterations in serum hormone levels, and other data
suggest that LCTs were mediated through a perturbation of the HPG-axis. Data
suggest that this occurs after a threshold of exposure is reached, indicating a
nonlinear/threshold dose-response. Pronamide-induced rat LCTs mediated by
alterations to the HPG-axis have low relevance to humans due to quantitative
differences in sensitivity between rats and humans to LCTs. Pronamide displayed
no genotoxicity or direct endocrine effects. A margin of exposure approach for
risk assessment and derivation of the chronic reference dose based on a point of
departure of 200ppm is most appropriate and protective of human health.
PMID- 25846365
TI - An improved method for the isolation of rat alveolar type II lung cells: Use in
the Comet assay to determine DNA damage induced by cigarette smoke.
AB - Smoking is a cause of serious diseases, including lung cancer, emphysema, chronic
bronchitis and heart disease. DNA damage is thought to be one of the mechanisms
by which cigarette smoke (CS) initiates disease in the lung. Indeed, CS induced
DNA damage can be measured in vitro and in vivo. The potential of the Comet assay
to measure DNA damage in isolated rat lung alveolar type II epithelial cells (AEC
II) was explored as a means to include a genotoxicity end-point in rodent sub
chronic inhalation studies. In this study, published AEC II isolation methods
were improved to yield viable cells suitable for use in the Comet assay. The
improved method reduced the level of basal DNA damage and DNA repair in isolated
AEC II. CS induced DNA damage could also be quantified in isolated cells
following a single or 5 days CS exposure. In conclusion, the Comet assay has the
potential to determine CS or other aerosol induced DNA damage in AEC II isolated
from rodents used in sub-chronic inhalation studies.
PMID- 25846366
TI - Pronamide: Weight of evidence for potential estrogen, androgen or thyroid
effects.
AB - Based on the exposure potential to humans and environment, pronamide was one of
52 chemicals on the first list evaluated under US EPA's Endocrine Disruptor
Screening Program (EDSP). The purpose of EDSP is to screen chemicals for their
potential to interact with estrogen-, androgen-, or thyroid-signaling pathways. A
battery of 11 Tier 1 assays was completed for pronamide in accordance with EDSP
test guidelines. In addition, Other Scientifically Relevant Information, which
included existing data from regulatory guideline studies and published
literature, was used in a weight-of-evidence (WoE) evaluation of potential
endocrine activity. The WoE conclusion is that pronamide does not interact
directly with estrogen, androgen, or thyroid receptors or post-receptor events.
Across in vivo studies, the liver is consistently and reproducibly the target
organ for pronamide's effects. Pronamide activates hepatocytic nuclear receptors
(including constitutive androstane receptor), induces hepatic enzymes, produces
hepatocellular hypertrophy and increases liver weights. These changes are coupled
with increased metabolic activity and a subsequent increased metabolism and/or
clearance of both steroid and thyroid hormones. Thus, while pronamide alters some
endocrine-sensitive endpoints in EDSP Tier 1 assays, effects on liver metabolism
likely explain altered hormone levels and indirect endocrine changes.
PMID- 25846367
TI - Relevance of the mouse skin initiation-promotion model for the classification of
carcinogenic substances encountered at the workplace.
AB - The Permanent Senate Commission for the Investigation of Health Hazards of
Chemical Compounds in the Work Area (MAK Commission of the Deutsche
Forschungsgemeinschaft) evaluates chemical substances using scientific criteria
to prevent adverse effects on health at the work place. As part of this task
there is a need to evaluate tumor promoting activity of chemicals (enhancement of
formation of squamous cell carcinomas via premalignant papillomas) obtained from
two-stage initiation/promotion experiments using the mouse skin model. In the
present communication we address this issue by comparing responses seen in mouse
skin with those in humans. We conclude that tumor promotional effects seen in
such animal models be carefully analyzed on a case by case basis. Substances that
elicit a rather non-specific effect that is restricted to the high dose range are
considered to be irrelevant to humans and thus do not require classification as
carcinogens. In contrast, substances that might have both a mode of action and a
potency similar to the specific effects seen with TPA (12-O-tetradecanoylphorbol
13-acetate), the prototype tumor promoter in mouse skin, which triggers receptor
mediated signal cascades in the very low dose range, have to be classified in a
category for carcinogens.
PMID- 25846368
TI - Elevated tissue Cr levels, increased plasma oxidative markers, and global
hypomethylation of blood DNA in male Sprague-Dawley rats exposed to potassium
dichromate in drinking water.
AB - Hexavalent chromium [Cr (VI)] is prevalent in ground water in some areas, but
evidence on the toxic effects of Cr (VI) via ingestion through drinking water
remains insufficient. The aims of our study were to investigate the toxic effects
of Cr (VI) through oral water ingestion on oxidative stress and DNA methylation.
Thirty-two Sprague-Dawley rats were randomly divided into four groups, and
exposed to porassium dichromate (K2 Cr2 O7 ; 0, 30, 100, and 300 mg/L) in
drinking water for 4 weeks. Mean body weight gain, mean water consumption,
clinical chemistry determinations, and oxidative stress levels in plasma were
measured. Global DNA methylation changes and DNA methylation status at the
promoter of p16 gene were also detected. After 4 weeks, mild anemic effects and
increased plasma malondialdehyde (MDA) levels occurred in rats exposed to 100
mg/L or 300 mg/L of Cr (VI). Plasma glutathione peroxidase (GSH-Px) activity
decreased in all exposed groups. Global DNA methylation levels were reduced in
100 mg/L and 300 mg/L exposure groups. However, DNA methylation status at the
promoter of P16 gene remained unchanged in all K2 Cr2 O7- treated groups. The
correlation analysis indicated that increased MDA levels were closely correlated
to global DNA hypomethylation. Our results indicated that oral ingestion of Cr
(VI) through drinking water caused not only oxidative stress in plasma, but also
global DNA hypomethylation in blood cells from male rats, and a good correlation
was found between increased MDA levels and reduced global DNA methylation. (c)
2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1080-1090, 2016.
PMID- 25846369
TI - A hybrid adsorbent/visible light photocatalyst for the abatement of microcystin
LR in water.
AB - A hybrid adsorbent/photocatalyst was obtained and used for the removal of
microcystin-LR, a potent toxin, from water via adsorption and photocatalyzed
oxidation with singlet oxygen. The combined adsorption/photooxidation processes
yielded a 500-fold decrease of the overall MC-LR concentration. The
adsorbent/photocatalyst can be easily removed from the reaction system by
sedimentation or centrifugation.
PMID- 25846370
TI - Tetranectin positive expression in tumour tissue leads to longer survival in
Danish women with ovarian cancer. Results from the 'Malova' ovarian cancer study.
AB - The primary objective of this study was to analyse Tetranectin (TN) expression in
tumour tissues and TN serum concentration in 758 women with epithelial ovarian
tumours. The second was to evaluate, whether TN tissue expression levels
correlate with clinico-pathological parameters and prognosis of the disease.
Using tissue arrays we analysed the expression levels in tissues from 166 women
with borderline ovarian tumours (BOTs) and 592 women with ovarian cancer (OC). A
panel of three antibodies was used for immunohistochemistry: a polyclonal and two
monoclonal antibodies. Serum TN was measured using the polyclonal antibody A-371.
Univariate survival analyses stratified for chemotherapy showed that positive
tissue TN as demonstrated by the polyclonal antibody indicated a significantly
longer overall survival (OS) (p = 0.0001) as well as cancer specific survival
(CSS) (p < 0.0001). High serum TN was likewise found to imply longer OS (p <
0.0001) and CSS (p < 0.0001), whereas tissue staining with the two monoclonal
antibodies failed to demonstrate any significant correlation with either survival
type. Univariate Kaplan-Meier survival analysis performed on all OC cases showed
a significantly longer OS (p = 0.0009) and CSS (p = 0.0006) for women with TN
positive tumour tissue and in women with high serum TN levels (p < 0.0001 for
both). However, in the multivariate Cox regression analysis, only serum TN was
found to be an independent prognostic factor for OS (p = 0.01) and not for CSS (p
= 0.08). In conclusion, our results predict that a positive TN expression of both
tumour tissue and serum points to a more favourable outcome for OC patients.
PMID- 25846371
TI - Photoisomerisation in Aminoazobenzene-Substituted Ruthenium(II) Tris(bipyridine)
Complexes: Influence of the Conjugation Pathway.
AB - Transition-metal complexes containing stimuli-responsive systems are attractive
for applications in optical devices, photonic memory, photosensing, as well as
luminescence imaging. Amongst them, photochromic metal complexes offer the
possibility of combining the specific properties of the metal centre and the
optical response of the photochromic group. The synthesis, the electrochemical
properties and the photophysical characterisation of a series of donor-acceptor
azobenzene derivatives that possess bipyridine groups connected to a 4
dialkylaminoazobenzene moiety through various linkers are presented. DFT and TD
DFT calculations were performed to complement the experimental findings and
contribute to their interpretation. The position and nature of the linker
(ethynyl, triazolyl, none) were engineered and shown to induce different
electronic coupling between donor and acceptor in ligands and complexes. This in
turn led to strong modulations in terms of photoisomerisation of the ligands and
complexes.
PMID- 25846380
TI - Interventional MR elastography for MRI-guided percutaneous procedures.
AB - PURPOSE: MRI-guided thermal ablations require reliable monitoring methods to
ensure complete destruction of the diseased tissue while avoiding damage to the
surrounding healthy tissue. Based on the fact that thermal ablations result in
substantial changes in biomechanical properties, interventional MR elastography
(MRE) dedicated to the monitoring of MR-guided thermal therapies is proposed
here. METHODS: Interventional MRE consists of a needle MRE driver, a fast and
interactive gradient echo pulse sequence with motion encoding, and an inverse
problem solver in real-time. This complete protocol was tested in vivo on swine
and the ability to monitor elasticity changes in real-time was assessed in
phantom. RESULTS: Thanks to a short repetition time, a reduction of the number of
phase-offsets and the use of a sliding window, one refreshed elastogram was
provided every 2.56 s for an excitation frequency of 100 Hz. In vivo elastograms
of swine liver were successfully provided in real-time during one breath-hold.
Changes of elasticity were successfully monitored in a phantom during its
gelation with the same elastogram frame rate. CONCLUSION: This study demonstrates
the ability of detecting elasticity changes in real-time and providing
elastograms in vivo with interventional MRE that could be used for the monitoring
of thermal ablations.
PMID- 25846372
TI - Sialylation regulates brain structure and function.
AB - Every cell expresses a molecularly diverse surface glycan coat (glycocalyx)
comprising its interface with its cellular environment. In vertebrates, the
terminal sugars of the glycocalyx are often sialic acids, 9-carbon backbone
anionic sugars implicated in intermolecular and intercellular interactions. The
vertebrate brain is particularly enriched in sialic acid-containing glycolipids
termed gangliosides. Human congenital disorders of ganglioside biosynthesis
result in paraplegia, epilepsy, and intellectual disability. To better understand
sialoglycan functions in the nervous system, we studied brain anatomy, histology,
biochemistry, and behavior in mice with engineered mutations in St3gal2 and
St3gal3, sialyltransferase genes responsible for terminal sialylation of
gangliosides and some glycoproteins. St3gal2/3 double-null mice displayed
dysmyelination marked by a 40% reduction in major myelin proteins, 30% fewer
myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions
at nodes of Ranvier. In part, these changes may be due to dysregulation of
ganglioside-mediated oligodendroglial precursor cell proliferation. Neuronal
markers were also reduced up to 40%, and hippocampal neurons had smaller
dendritic arbors. Young adult St3gal2/3 double-null mice displayed impaired motor
coordination, disturbed gait, and profound cognitive disability. Comparisons
among sialyltransferase mutant mice provide insights into the functional roles of
brain gangliosides and sialoglycoproteins consistent with related human
congenital disorders.
PMID- 25846381
TI - Sequence-tagged high-density genetic maps of Zoysia japonica provide insights
into genome evolution in Chloridoideae.
AB - Zoysiagrass (Zoysia spp.), belonging to the genus Zoysia in the subfamily
Chloridoideae, is widely used in domestic lawns, sports fields and as forage. We
constructed high-density genetic maps of Zoysia japonica using a restriction site
associated DNA sequencing (RAD-Seq) approach and an F1 mapping population derived
from a cross between 'Carrizo' and 'El Toro'. Two linkage maps were constructed,
one for each of the parents. A map consisting of 2408 RAD markers distributed on
21 linkage groups was constructed for 'Carrizo'. Another map with 1230 RAD
markers mapped on 20 linkage groups was constructed for 'El Toro'. The average
distance between adjacent markers of the two maps was at 0.56 and 1.4 cM,
respectively. Comparative genomics analysis was carried out among zoysiagrass,
rice and sorghum genomes and a highly conserved collinearity in the gene order
was observed among the three genomes. Chromosome collinearity was disrupted at
centromeric regions for each chromosome pair between zoysiagrass and sorghum
genomes. However, no obvious synteny gaps were observed across the centromeric
regions between zoysiagrass and rice genomes. Two homologous chromosomes for each
of the 10 sorghum chromosomes were found in the zoysiagrass genome, indicating an
allotetraploid origin for zoysiagrass. The reduction of the basic chromosome
number from 12 to 10 in chloridoids and panicoids took place via independent
single-step nested chromosome fusion events after the two subfamilies diverged
from a common ancestor. The genetic maps will assist in genome sequence assembly,
targeted gene isolation and comparative genomic analyses among grasses.
PMID- 25846382
TI - Erratum to: Activation of Toll-like receptor 3 increases mouse aortic vascular
smooth muscle cell contractility through ERK1/2 pathway.
PMID- 25846383
TI - Housing Satisfaction of Older (55+) Single-Person Householders in U.S. Rural
Communities.
AB - This study aims to understand the housing satisfaction of older (55+) single
person householders in U.S. rural communities using the available variables from
a secondary data set, the 2011 American Housing Survey (AHS). In this study,
housing satisfaction was considered to be an indicator of quality of life. Based
on previous studies, we developed a model to test a hypothesized relationship
between older (55+) single-person householders' (N = 1,017) housing satisfaction
and their personal, physical, financial, and environmental characteristics.
Multiple regression results showed that the model was supported, indicating that
significant variables in housing satisfaction include age, gender, health status,
age of house, structure type, and unit location. Among the significant variables,
health status was revealed to be the strongest factor in housing satisfaction.
Housing satisfaction was discussed as potential indicators of quality of life.
PMID- 25846384
TI - Predictors of hypophosphatemia during refeeding of patients with severe anorexia
nervosa.
AB - OBJECTIVE: Hypophosphatemia of refeeding is one of the most dangerous
complications seen during the treatment of patients with anorexia nervosa.
Although easily detectable and treatable, hypophosphatemia is under-recognized as
a complication of refeeding. Specific risk factors for the development of
hypophosphatemia are likely to exist among patients with severe anorexia nervosa.
The purpose of this study was to identify clinically useful markers that may
predict the development of or protection from hypophosphatemia during refeeding.
METHODS: We conducted a retrospective case-control study of 123 patients with
severe anorexia nervosa admitted for medical stabilization at the ACUTE Center
for Eating Disorders between October 1, 2008 and December 31, 2013. Risk factors
for refeeding hypophosphatemia were determined by multivariate logistic
regression from clinical parameters and laboratory values measured at the time of
admission. RESULTS: The prevalence of hypophosphatemia was 33.3% (41 of 123
patients). Higher hemoglobin was the only risk factor associated with a higher
odds of developing hypophosphatemia (adjusted odds ratio [aOR], 1.56 [95%
confidence interval [CI], 1.12-2.18]). Statistically significant protective
factors against the development of hypophosphatemia were observed with higher
body mass index (aOR, 0.54 [95% CI, 0.39-0.75]), higher serum potassium (aOR,
0.29 [95% CI, 0.14-0.62]), and higher serum prealbumin (aOR, 0.91 [95% CI, 0.84
0.99]). DISCUSSION: Four independent factors associated with refeeding
hypophosphatemia were identified. Identification of findings which correlate with
hypophosphatemia, or the lack thereof, has the potential to facilitate
appropriate triage of patients with anorexia nervosa for closer monitoring during
refeeding.
PMID- 25846385
TI - Editorial: impaired fasting pyloric compliance in gastroparesis and the benefits
of therapeutic pyloric dilatation.
PMID- 25846386
TI - Editorial: impaired fasting pyloric compliance in gastroparesis and the benefits
of therapeutic pyloric dilatation--authors' reply.
PMID- 25846387
TI - Letter: portal vein obstruction--which subset of patients could benefit the most?
PMID- 25846388
TI - Letter: portal vein obstruction--which subset of patients could benefit the most?
Authors' reply.
PMID- 25846389
TI - Letter: future directions for epidemiological studies of Barrett's oesophagus.
PMID- 25846390
TI - Letter: HIV-associated NAFLD--more questions than answers?
PMID- 25846391
TI - Letter: HIV-associated NAFLD--more questions than answers? Authors' reply.
PMID- 25846392
TI - Letter: depression and the use of anti-depressants in patients with chronic liver
disease or liver transplantation.
PMID- 25846393
TI - Letter: depression and the use of anti-depressants in patients with chronic liver
disease or liver transplantation - authors' reply.
PMID- 25846394
TI - Wogonin induces apoptosis and endoplasmic reticulum stress in HL-60 leukemia
cells through inhibition of the PI3K-AKT signaling pathway.
AB - Wogonin is a flavonoid isolated from Scutellaria baicalensis root and has
multiple pharmacological effects, including anticancer effects. Recent studies
have shown that wogonin induces cell cycle arrest and reverses multi-drug
resistance in the human K562 leukemia cell line. However, its pharmacological
function in the apoptosis of leukemia cells remains unknown. Therefore, we
hypothesized that wogonin can induce apoptosis in the HL-60 leukemia cell line.
In the present study, the HL-60 cells were treated with different doses of
wogonin (0-150 uM). Wogonin inhibited the viability of HL-60 cells in a dose
dependent and time-dependent manner. Flow cytometry and analyses of caspase and
PARP-1 activation and the Bax/Bcl-2 ratio, demonstrated that the cytotoxic effect
of wogonin on HL-60 cells was mediated by caspase-dependent and mitochondrial
dependent apoptosis. Wogonin also induced the expression of certain members of
the endoplasmic reticulum (ER) stress pathway (CHOP, GRP94 and GRP78) and the
activation of multiple branches of ER stress transducers (IRE1alpha, PERK
eIF2alpha and ATF6) in the HL-60 cells. In addition, wogonin reduced the
phosphorylation of PI3K and AKT in the HL-60 cells. Furthermore, constitutive
activation of AKT induced by adenoviral vectors inhibited the pro-apoptotic
effects and ER stress induced by wogonin in the HL-60 cells. In summary, our
results indicated that wogonin induced apoptosis and ER stress in HL-60 cells,
which was mediated by the inhibition of the PI3K-AKT signaling pathway.
PMID- 25846395
TI - Diagnostic utility of measuring free light chains in the cerebrospinal fluid of
patients with multiple myeloma.
PMID- 25846396
TI - Intracellular Delivery of Bioactive Cargos to Hard-to-Transfect Cells Using
Carbon Nanosyringe Arrays under an Applied Centrifugal g-Force.
AB - There is considerable interest in developing a common, universal platform for
delivering biomacromolecules such as proteins and RNAs into diverse cells with
high efficiency. Here, it is shown that carbon nanosyringe arrays (CNSAs) under
an applied centrifugal g-force (cf-CNSAs) can deliver diverse bioactive cargos
directly into the cytosol of hard-to-transfect cells with relatively high
efficiency and reproducibility. The cf-CNSA platform, an optimized version of a
previous CNSA-mediated intracellular delivery platform that adds a g-force
feature, exhibits more rapid and superior delivery of cargos to various hard-to
transfect cells than is the case in the absence of g-force. Active species,
including small interfering RNAs, plasmids, and proteins are successfully
transported across plasma membrane barriers into various cells. By overcoming the
limitations of currently available transfection methods, the cf-CNSA platform
paves the way to universal delivery of a variety of cargos, facilitating the
analysis of cellular responses in diverse cell types.
PMID- 25846397
TI - Stratified scaffold design for engineering composite tissues.
AB - A significant challenge to orthopaedic soft tissue repair is the biological
fixation of autologous or allogeneic grafts with bone, whereby the lack of
functional integration between such grafts and host bone has limited the clinical
success of anterior cruciate ligament (ACL) and other common soft tissue-based
reconstructive grafts. The inability of current surgical reconstruction to
restore the native fibrocartilaginous insertion between the ACL and the femur or
tibia, which minimizes stress concentration and facilitates load transfer between
the soft and hard tissues, compromises the long-term clinical functionality of
these grafts. To enable integration, a stratified scaffold design that mimics the
multiple tissue regions of the ACL interface (ligament-fibrocartilage-bone)
represents a promising strategy for composite tissue formation. Moreover,
distinct cellular organization and phase-specific matrix heterogeneity achieved
through co- or tri-culture within the scaffold system can promote biomimetic
multi-tissue regeneration. Here, we describe the methods for fabricating a tri
phasic scaffold intended for ligament-bone integration, as well as the tri
culture of fibroblasts, chondrocytes, and osteoblasts on the stratified scaffold
for the formation of structurally contiguous and compositionally distinct regions
of ligament, fibrocartilage and bone. The primary advantage of the tri-phasic
scaffold is the recapitulation of the multi-tissue organization across the native
interface through the layered design. Moreover, in addition to ease of
fabrication, each scaffold phase is similar in polymer composition and therefore
can be joined together by sintering, enabling the seamless integration of each
region and avoiding delamination between scaffold layers.
PMID- 25846398
TI - Flow cytometric assays for the study of autophagy.
AB - The use of flow cytometry to study the autophagic process has recently led to the
development of numerous assays measuring various aspects of the autophagic
process. These include the detection of the autophagy marker, the microtubule
associated protein LC3B, cell cycle analysis of LC3B expression, increase in
lysosomal mass, as well as organelle specific autophagy and the measurement of
mitochondrial function. We employed a range of autophagy inducing agents to
determine the degree of LC3B up-regulation and corresponding cell cycle
distribution, increase in lysosomal mass and mitochondrial dysfunction, as well
as the relative preference for the specific type of microautophagy or organelle
phagy. A variety of autophagy inducing agents were compared these included
rapamycin, chloroquine, various nutrient starvation treatments on two cell types,
Jurkat T-cell leukaemia and K562 erythromyeloid leukaemia cell lines. Given that
numerous autophagy inducing agents cause cell cycle arrest, the cell cycle phase
distribution was investigated and LC3B antigen was shown to increase as cells
progressed through the cell cycle. LysoTracker dyes have been previously employed
to investigate the autophagic process and here the LysoTracker signal increased
in autophagic cells in relation to controls. Organelle autophagy of mitochondria
and Endoplasmic Reticulum (ER), termed mitophagy and ER phagy was determined flow
cytometrically by the employment of organelle mass probes, MitoTracker Green
(MTG) and ER Tracker Green (ERTG). A modification of the cell cycle analysis
width and area analysis employed for DNA content determinations was developed to
show changes in organelle mass on a linear scale. Relative changes in linear
scaled median fluorescence intensity (MFI) was compared to control cells to
determine the degree and type of organelle phagy induced by a range of autophagy
inducing agents and treatments. These flow cytometric organelle phagy and
lysosome mass assays can be used by researchers to study the autophagic process
further in terms of cell and mitochondrial functionality over time in a cell
dependent manner as an adjunct to LC3B measurements.
PMID- 25846399
TI - Click-crosslinked injectable hyaluronic acid hydrogel is safe and biocompatible
in the intrathecal space for ultimate use in regenerative strategies of the
injured spinal cord.
AB - Traumatic spinal cord injury (SCI) causes damage and degeneration at and around
the lesion site resulting in a loss of function. SCI presents a complex
regenerative problem due to the multiple aspects of growth inhibition and the
heterogeneity in size, shape and extent of injury. Currently, there is no widely
accepted treatment strategy available and delivering biomolecules to the central
nervous system remains a challenge. With a view towards achieving local release,
we designed a hydrogel that can be injected into the intrathecal space. Here we
describe the synthesis and characterization of a click-crosslinked hyaluronic
acid hydrogel and demonstrate controlled in vitro release of bioactive brain
derived neurotrophic factor. Importantly, we demonstrate that this new hydrogel
is both biocompatible in the intrathecal space based on immunohistochemistry of
the host tissue response and safe based on behavioral analysis of locomotor
function.
PMID- 25846401
TI - Papillary fill response in single-tooth implants using abutments of different
geometry.
AB - OBJECTIVE: To evaluate the influence of abutment geometry on papillary fill in
the esthetic zone in a delayed crown protocol. MATERIALS AND METHODS: Twenty-six
subjects received two non-adjacent endosseous implants in the esthetic zone.
Functional temporary crowns were installed 17-19 weeks later, using conventional
(control) and curved (experimental) abutments. The abutments were randomized in
each patient independently. Final crowns were cemented after 2 months (T0).
Standard intraoral photographs and radiographs were made to evaluate papillary
fill after 12 months (T12). The interproximal papilla fill was measured by means
of the papilla index score (PIS) and related to the maximum bone level between
the implant and the adjacent root as well as the peri-implant marginal bone level
at T12, both measured radiographically. RESULTS: No statistically significant
difference between the experimental and the control group could be demonstrated
(P = 0.25). Ordinal regression analysis showed a positive correlation between the
maximum bone level and papilla fill (P < 0.01) and a negative correlation between
the peri-implant marginal bone level and papilla fill (P < 0.05). CONCLUSION: A
concave abutment does not exhibit a better fill of the papilla compared with a
straight abutment in single-tooth implant placement using a delayed protocol in
the esthetic zone after 12 months of function.
PMID- 25846400
TI - Extracellular zinc induces phosphoethanolamine addition to Pseudomonas aeruginosa
lipid A via the ColRS two-component system.
AB - Gram-negative bacteria survive harmful environmental stressors by modifying their
outer membrane. Much of this protection is afforded upon remodeling of the lipid
A region of the major surface molecule lipopolysaccharide (LPS). For example, the
addition of cationic substituents, such as 4-amino-4-deoxy-L-arabinose (L-Ara4N)
and phosphoehthanolamine (pEtN) at the lipid A phosphate groups, is often induced
in response to specific environmental flux stabilizing the outer membrane. The
work herein represents the first report of pEtN addition to Pseudomonas
aeruginosa lipid A. We have identified the key pEtN transferase which we named
EptAPa and characterized its strict activity on only one position of lipid A,
contrasting from previously studied EptA enzymes. We further show that
transcription of eptAP a is regulated by zinc via the ColRS two-component system
instead of the PmrAB system responsible for eptA regulation in E. coli and
Salmonella enterica. Further, although L-Ara4N is readily added to the same
position of lipid A as pEtN under certain environmental conditions, ColR
specifically induces pEtN addition to lipid A in lieu of L-Ara4N when Zn2+ is
present. The unique, specific regulation of eptAP a transcription and enzymatic
activity described in this work demonstrates the tight yet inducible control over
LPS modification in P. aeruginosa.
PMID- 25846402
TI - Re-examining the origin and function of liver-resident NK cells.
AB - Recent studies have identified a population of liver-resident innate lymphoid
cells (ILCs) that, based on the expression of certain phenotypic markers, were
termed 'liver-resident NK cells' and considered to be a new subset of
conventional natural killer (cNK) cells. However, different transcriptional
networks control the development of liver-resident NK cells and cNK cells and,
furthermore, these cells exhibit features that characterize mucosal ILC1s. Here,
we review findings providing insight into the origin, phenotype, and function of
liver-resident NK cells, and discuss these in the context of the current
understanding of lineage relations of ILC subsets. We propose that the
similarities between liver-resident NK cells and mucosal ILC1s should be
considered when revising the categorization framework for these cells, and
discuss implications of this revision for other tissue-specific NK cells.
PMID- 25846403
TI - First trimester screening for Down syndrome using nuchal translucency, maternal
serum pregnancy-associated plasma protein A, free-beta human chorionic
gonadotrophin, placental growth factor, and alpha-fetoprotein.
AB - OBJECTIVE: The aim of this study was to assess the screening performance for Down
syndrome using first trimester combined screening (FTS) and two additional
markers, serum placental growth factor (PlGF) and alpha-fetoprotein (AFP).
METHODS: This is a retrospective case-control study of 137 pregnancies affected
by Down syndrome and 684 individually matched unaffected pregnancies. Stored
serum samples were tested for all four markers, and results were expressed as
multiples of the gestation-specific median (MoM). Multivariate Gaussian modeling
was used to calculate risks for different combinations of markers and to predict
the detection rate (DR) and false positive rate (FPR). The predicted performance
of enhanced FTS (FTS plus PlGF and AFP) was compared with FTS; the performance
without nuchal translucency (first trimester quad) was assessed. RESULTS: For
affected pregnancies, the median PlGF level was 0.622 MoM and median AFP 0.764
MoM. Adding PlGF and AFP improved the screening performance. At 3% FPR, DR
increased by 4.4% from 83.8% to 88.2% using enhanced FTS; at 95% DR, FPR
decreased by 8.3%, from 19.3% to 11.0%. At 3% FPR, DR using first trimester quad
test was 76.4%. CONCLUSIONS: The performance of FTS can be enhanced by adding
PlGF and AFP. Even without nuchal translucency, the test would perform well.
PMID- 25846404
TI - Use of loop-mediated isothermal amplification to detect six groups of pathogens
causing secondary lower respiratory bacterial infections in horses.
AB - Microbial substitution occasionally occurs following the administration of
antimicrobials to horses that have pneumonia or pleuropneumonia. Four specific
loop-mediated isothermal amplification (LAMP) assays were developed to detect
some equine respiratory pathogens, namely strains of the Bacteroides-Prevotella
group, Klebsiella pneumoniae, Stenotrophomonas maltophilia, and Staphylococcus
aureus. These four LAMP assays and two previously published LAMP assays targeting
Escherichia coli or Pseudomonas aeruginosa were used on clinical respiratory
specimens and a high accordance found between the results of the LAMP assays and
bacterial culture. Use of these LAMP assays could enable rapid detection of
pathogenic bacteria and swift administration of the appropriate antimicrobials.
PMID- 25846405
TI - Crystal structures, phase transitions, and switchable dielectric behaviors:
comparison of a series of N-heterocyclic ammonium perchlorates.
AB - Three analogue N-heterocyclic complexes, 1-propyl-1-methylpiperidinium
perchlorate (, [PMpip][ClO4]), 1-cyanomethyl-1-methylpiperidinium perchlorate (,
[CMpip][ClO4]), and 1-cyanomethyl-1-methylmorpholinium perchlorate (,
[CMmor][ClO4]) are identified as phase transition materials displaying switchable
dielectric behaviors. Despite the common [ClO4](-) anion and the closely related
cations, compound crystallizes in the orthorhombic space group P212121, but
compounds and belong to the monoclinic space group P21/n with distinct cell
dimensions. Compounds , and undergo reversible phase transitions around 199, 387
and 416 K, respectively, accompanied by notable step-like dielectric anomalies
which could be switched by the phase transition and be tuned in distinct
dielectric states. The respective dielectric constants in the high dielectric
states are 1.2, 2.2 and 3.2 times that in the low dielectric states for compounds
, and . Generally, these differences in the phase transitions and dielectric
properties are caused by the distinct molecular structures and hydrogen-bonding
conformations resulting from the structural variations in the side-chain and the
ring structure.
PMID- 25846407
TI - Identification of the Mamestra configurata (Lepidoptera: Noctuidae) peritrophic
matrix proteins and enzymes involved in peritrophic matrix chitin metabolism.
AB - The peritrophic matrix (PM) is essential for insect digestive system physiology
as it protects the midgut epithelium from damage by food particles, pathogens,
and toxins. The PM is also an attractive target for development of new pest
control strategies due to its per os accessibility. To understand how the PM
performs these functions, the molecular architecture of the PM was examined using
genomic and proteomic approaches in Mamestra configurata (Lepidoptera:
Noctuidae), a major pest of cruciferous oilseed crops in North America. Liquid
chromatography-tandem mass spectrometry analyses of the PM identified 82 proteins
classified as: (i) peritrophins, including a new class with a CBDIII domain; (ii)
enzymes involved in chitin modification (chitin deacetylases), digestion (serine
proteases, aminopeptidases, carboxypeptidases, lipases and alpha-amylase) or
other reactions (beta-1,3-glucanase, alkaline phosphatase, dsRNase, astacin,
pantetheinase); (iii) a heterogenous group consisting of polycalin, REPATs,
serpin, C-Type lectin and Lsti99/Lsti201 and 3 novel proteins without known
orthologs. The genes encoding PM proteins were expressed predominantly in the
midgut. cDNAs encoding chitin synthase-2 (McCHS-2), chitinase (McCHI), and beta-N
acetylglucosaminidase (McNAG) enzymes, involved in PM chitin metabolism, were
also identified. McCHS-2 expression was specific to the midgut indicating that it
is responsible for chitin synthesis in the PM, the only chitinous material in the
midgut. In contrast, the genes encoding the chitinolytic enzymes were expressed
in multiple tissues. McCHS-2, McCHI, and McNAG were expressed in the midgut of
feeding larvae, and NAG activity was present in the PM. This information was used
to generate an updated model of the lepidopteran PM architecture.
PMID- 25846406
TI - Notch receptor expression in human brain arteriovenous malformations.
AB - The roles of the Notch pathway proteins in normal adult vascular physiology and
the pathogenesis of brain arteriovenous malformations are not well-understood.
Notch 1 and 4 have been detected in human and mutant mice vascular malformations
respectively. Although mutations in the human Notch 3 gene caused a genetic form
of vascular stroke and dementia, its role in arteriovenous malformations
development has been unknown. In this study, we performed immunohistochemistry
screening on tissue microarrays containing eight surgically resected human brain
arteriovenous malformations and 10 control surgical epilepsy samples. The tissue
microarrays were evaluated for Notch 1-4 expression. We have found that compared
to normal brain vascular tissue Notch-3 was dramatically increased in brain
arteriovenous malformations. Similarly, Notch 4 labelling was also increased in
vascular malformations and was confirmed by western blot analysis. Notch 2 was
not detectable in any of the human vessels analysed. Using both
immunohistochemistry on microarrays and western blot analysis, we have found that
Notch-1 expression was detectable in control vessels, and discovered a
significant decrease of Notch 1 expression in vascular malformations. We have
demonstrated that Notch 3 and 4, and not Notch 1, were highly increased in human
arteriovenous malformations. Our findings suggested that Notch 4, and more
importantly, Notch 3, may play a role in the development and pathobiology of
human arteriovenous malformations.
PMID- 25846408
TI - Cloning and tissue distribution of appetite-regulating peptides in pirapitinga
(Piaractus brachypomus).
AB - Pirapitinga (or red-bellied pacu, Piaractus brachypomus, Characiforme,
Serrasalmidae) is an economically important South American fish for which the
endocrine mechanism of the regulation of feeding has never been examined. To
better understand these mechanisms, cDNAs encoding the appetite-regulating
peptides orexin, cocaine- and amphetamine-regulated transcript (CART), apelin,
cholecystokinin (CCK), peptide YY (PYY), leptin and ghrelin were isolated in
pirapitinga and their mRNA distributions examined in peripheral tissues and
brain. When compared to other fish, the sequences obtained for all peptides were
most similar to those of other Characiforme fish (i.e. Mexican cavefish) and
Siluriformes (catfish) as well as Cypriniformes (i.e. goldfish, zebrafish). All
peptides were widely expressed within the brain. With the exception of CART,
which was only expressed in brain, the mRNAs of all peptides were present in
several peripheral tissues, including gastrointestinal tract, kidneys and gills.
The widespread and peptide-specific distributions suggest that each peptide might
have distinct physiological actions in the brain and on peripheral tissues, in
particular on the gastrointestinal tract, which include feeding regulation. This
preliminary study opens new avenues for further functional studies on the
endocrine regulation of feeding in Serrasalmidae fish, including pirapitinga.
PMID- 25846409
TI - Idiopathic phrenic neuropathies: A case series and review of the literature.
AB - INTRODUCTION: Phrenic neuropathies (PNs) are a major cause of dyspnea, orthopnea,
and hypercapnic respiratory failure. The aim of the study was to obtain
diagnostic findings, assess therapeutic options, and review outcomes in PN
patients. METHODS: From 2004 to 2013, patients with PN referred to the author's
institution were studied using clinical, pulmonary function, and
electrodiagnostic tests. A PubMed search of published PN reports was also done.
Unilateral PN (UPN) and bilateral PN (BPN) patients were compared. RESULTS: The
analysis consisted of 10 UPN and 9 BPN patients seen by the author, plus previous
reports of 18 UPN and 40 BPN patients. BPN patients were older (in the author's
series) and were more often hypertensive. They reported pain less often, dyspnea
and orthopnea more often, and had worse results on pulmonary function tests than
UPN patients. CONCLUSIONS: UPN and BPN are probably 2 variants of the same,
immune-mediated focal neuropathy. Electrodiagnosis is a valuable confirmatory
test for PN.
PMID- 25846411
TI - Crystal structure of a novel two domain GH78 family alpha-rhamnosidase from
Klebsiella oxytoca with rhamnose bound.
AB - The crystal structure of the GH78 family alpha-rhamnosidase from Klebsiella
oxytoca (KoRha) has been determined at 2.7 A resolution with rhamnose bound in
the active site of the catalytic domain. Curiously, the putative catalytic acid,
Asp 222, is preceded by an unusual non-proline cis-peptide bond which helps to
project the carboxyl group into the active centre. This KoRha homodimeric
structure is significantly smaller than those of the other previously determined
GH78 structures. Nevertheless, the enzyme displays alpha-rhamnosidase activity
when assayed in vitro, suggesting that the additional structural domains found in
the related enzymes are dispensible for function.
PMID- 25846410
TI - Obstructive heart defects associated with candidate genes, maternal obesity, and
folic acid supplementation.
AB - Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of
congenital heart defects, in which the heart valves, arteries, or veins are
abnormally narrow or blocked. Previous studies have suggested that the
development of OHDs involved a complex interplay between genetic variants and
maternal factors. Using the data from 569 OHD case families and 1,644 control
families enrolled in the National Birth Defects Prevention Study (NBDPS) between
1997 and 2008, we conducted an analysis to investigate the genetic effects of 877
single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with
the risk of OHDs, and their interactions with maternal use of folic acid
supplements, and pre-pregnancy obesity. Applying log-linear models based on the
hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR)
gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs.
In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and
BHMT2) were also identified to be associated with the occurrence of OHDs through
significant main infant genetic effects and interaction effects with maternal use
of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine
ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta
(DNMT3B) that were associated with elevated risk of OHDs among obese women. Our
findings suggested that the risk of OHDs was closely related to a combined effect
of variations in genes in the folate, homocysteine, or
glutathione/transsulfuration pathways, maternal use of folic acid supplements and
pre-pregnancy obesity.
PMID- 25846413
TI - Does the COPD assessment test (CAT(TM)) questionnaire produce similar results
when self- or interviewer administered?
AB - PURPOSE: The COPD assessment test (CAT) is a questionnaire that assesses the
impact of chronic obstructive pulmonary disease (COPD) on health status, but some
patients have difficulties filling it up by themselves. We examined whether the
mode of administration of the Spanish version of CAT (self vs. interviewer)
influences its scores and/or psychometric properties. METHODS: Observational,
prospective study in 49 Spanish centers that includes clinically stable COPD
patients (n = 153) and patients hospitalized because of an exacerbation (ECOPD; n
= 224). The CAT was self-administered (CAT-SA) or administered by an interviewer
(CAT-IA) based on the investigator judgment of the patient's capacity. To assess
convergent validity, the Saint George's Respiratory Disease Questionnaire (SGRQ)
and the London Chest Activity of Daily Living (LCADL) instrument were also
administered. Psychometric properties were compared across modes of
administration. RESULTS: A total of 118 patients (31 %) completed the CAT-SA and
259 (69 %) CAT-IA. Multiple regression analysis showed that mode of
administration did not affect CAT scores. The CAT showed excellent psychometric
properties in both modes of administration. Internal consistency coefficients
(Cronbach's alpha) were high (0.86 for CAT-SA and 0.85 for CAT-IA) as was test
retest reliability (intraclass correlation coefficients of 0.83 for CAT-SA and
CAT-IA). Correlations with SGRQ and LCADL were moderate to strong both in CAT-SA
and CAT-IA, indicating good convergent validity. Similar results were observed
when testing longitudinal validity. CONCLUSIONS: The mode of administration does
not influence CAT scores or its psychometric properties. Hence, both modes of
administration can be used in clinical practice depending on the physician
judgment of patient's capacity.
PMID- 25846412
TI - The Intestinal Gas Questionnaire: development of a new instrument for measuring
gas-related symptoms and their impact on daily life.
AB - BACKGROUND: Although gas-related symptoms (GRS) are common and intrusive, there
are no questionnaires to quantitate this problem. This study aimed to develop an
instrument to rectify this gap in our knowledge. METHODS: Concepts were initially
identified from the literature and interviews with gastroenterologists.
Exploratory one-to-one interviews and focus groups with irritable bowel syndrome
(IBS) patients (n = 28) and non-IBS subjects (n = 27) with GRS were conducted in
UK, France, and Spain leading to a conceptual framework for the questionnaire.
Last, iterative rounds of cognitive debriefing were performed with IBS (n = 16)
and non-IBS subjects (n = 14). KEY RESULTS: From the first three steps, nine GRS
(bloating, distension, flatulence, odorous flatulence, difficult gas evacuation,
stomach rumbling, belching, bad breath, and abdominal movement) were identified
although abdominal movement was subsequently excluded. Twelve quality of life
domains affected by these symptoms were identified as: Clothing, emotional,
physical appearance, diet, daily living, work, social life, physical activity,
relationships, sex life, sleep, and cognitive function. A 24-h recall for
symptoms and a 7-day recall for impact assessment were supported by the
qualitative findings. Cognitive debriefing confirmed the understanding of the
instrument. Across the three languages, the instrument was conceptually and
linguistically consistent. CONCLUSIONS & INFERENCES: The International Gas
Questionnaire is a 2-part instrument, developed rigorously and simultaneously in
three languages assessing seven symptoms (17 items) and their impact on 12
domains (26 items) in IBS and general population. It is now undergoing
psychometric validation and should provide a unique tool for epidemiological
surveys and clinical trials for developing new treatments for these symptoms.
PMID- 25846414
TI - Postoperative Atrial Fibrillation Predicts Long-Term Cardiovascular Events after
Radical Cystectomy.
AB - PURPOSE: Postoperative atrial fibrillation after radical cystectomy occurs in 2%
to 8% of cases. Recent evidence suggests that transient postoperative atrial
fibrillation leads to future cardiovascular events. The long-term cardiovascular
implications of postoperative atrial fibrillation in patients undergoing radical
cystectomy are largely unknown. MATERIALS AND METHODS: The Healthcare Cost and
Utilization Project State Inpatient Databases for California and Florida were
used to identify patients who underwent radical cystectomy between 2007 and 2010.
After excluding patients with a history of atrial fibrillation, coronary artery
disease and/or stroke, patients were matched using propensity scoring on age,
race, insurance status and preexisting comorbidities. Adjusted Kaplan-Meier time
to-event analysis and Cox proportional hazards models were used to assess the
effect of postoperative atrial fibrillation on cardiovascular events (acute
myocardial infarction and stroke) during postoperative year 1. RESULTS: Radical
cystectomy was performed in 4,345 patients who met the study inclusion criteria,
of whom 210 (4.8%) had postoperative atrial fibrillation. There was a
significantly higher cumulative incidence of cardiovascular events during the
first postoperative year in patients in whom postoperative atrial fibrillation
developed (24.8% vs 10.9%, adjusted log rank p=0.007). Cox proportional hazards
regression demonstrated an increased risk of cardiovascular events in patients
with postoperative atrial fibrillation (HR 10, p=0.02). CONCLUSIONS: Our results
demonstrate that patients undergoing radical cystectomy in whom transient
postoperative atrial fibrillation develops are at significantly increased risk
for cardiovascular events in the first postoperative year. Physicians should be
vigilant in assessing postoperative atrial fibrillation, even when transient, and
establish appropriate followup given the increased risk of cardiovascular
morbidity.
PMID- 25846415
TI - Comparative Effectiveness of Targeted vs Empirical Antibiotic Prophylaxis to
Prevent Sepsis from Transrectal Prostate Biopsy: A Retrospective Analysis.
AB - PURPOSE: We compared the effectiveness of targeted prophylaxis to the
effectiveness of empirical prophylaxis for preventing sepsis after transrectal
prostate biopsy using a retrospective multicenter quality improvement study.
MATERIALS AND METHODS: A total of 13 Kaiser Permanente urology departments
participated in a 1-year retrospective analysis of a quality improvement study.
In the targeted prophylaxis group rectal cultures were performed before
transrectal prostate biopsy and antibiotic sensitivities of Escherichia coli were
used to guide the selection of a single agent antibiotic for prophylaxis.
Cultures were plated on 10 MUg/ml ciprofloxacin infused MacConkey agar at a
central laboratory. Urologists using empirical prophylaxis continued the usual
regimen of ciprofloxacin monotherapy prophylaxis but sometimes added an
additional prophylactic antibiotic. The primary outcome of post-biopsy sepsis was
compiled by a search of the electronic medical record for the appropriate ICD-9
codes. RESULTS: A total of 5,355 prostate biopsy procedures were performed
between May 1, 2013 and April 30, 2014. Targeted prophylaxis was used in 1,802
procedures (34%) and empirical prophylaxis was used in 3,553 (66%). The overall
incidence of post-biopsy sepsis was 0.52% (28 of 5,355 cases). The incidence of
sepsis was 0.44% (8 of 1,802 cases) in the targeted prophylaxis group and 0.56%
(20 of 3,553) in the empirical prophylaxis group (p = 0.568). The prevalence of
ciprofloxacin resistant E. coli on rectal culture was 25% (444 of 1,802 cases).
Seven of the 8 patients (88%) on targeted prophylaxis in whom sepsis developed
used a prophylactic antibiotic to which the bacteria causing post-biopsy sepsis
were sensitive. CONCLUSIONS: The targeted prophylaxis protocol enabled physicians
to avoid using more than 1 broad-spectrum empirical antibiotic while
simultaneously achieving an overall rate of sepsis similar to the rate seen with
empirical prophylaxis.
PMID- 25846416
TI - Oncologic Efficacy of Radio Frequency Ablation for Small Renal Masses: Clear Cell
vs Papillary Subtype.
AB - PURPOSE: Current radio frequency ablation series do not distinguish renal cell
carcinoma subtypes when reporting oncologic efficacy. Papillary neoplasms may be
more amenable to radio frequency ablation than clear cell carcinoma because they
are less vascular, which may limit heat energy loss. We report the long-term
outcomes of patients treated with radio frequency ablation for small renal masses
by renal cell carcinoma subtype. MATERIALS AND METHODS: The records of patients
undergoing radio frequency ablation for small renal masses (cT1a) at 2
institutions from March 2007 to July 2012 were retrospectively reviewed. Patients
were included in analysis if they had biopsy confirmed clear cell or papillary
renal cell carcinoma histology. Patients had at least 1 contrast enhanced cross
sectional image following radio frequency ablation. Demographic data between
tumor subtypes were compared using the paired t-test. Oncologic outcomes were
determined by Kaplan-Meier survival analysis and survivor curves were compared
with the log rank test. RESULTS: A total of 229 patients met study inclusion
criteria. There were 181 clear cell tumors and 48 papillary tumors. Median
followup was 33.2 months. There was no difference between tumor groups based on
patient age, tumor size or grade, or months of followup. Five-year disease-free
survival was 89.7% for clear cell tumors and 100% for papillary tumors (p =
0.041). There was no significant difference in overall survival (88.4% vs 89.6%,
p = 0.764). CONCLUSIONS: Radio frequency ablation outcomes seem to be determined
in part by renal cell carcinoma subtype with clear cell renal tumors having less
favorable outcomes. We hypothesize that this is due to differences in tumor
vascularity. Our experience suggests that future tumor ablation studies should
consider reporting outcomes based on tumor cell types.
PMID- 25846417
TI - Outcomes of Ventral Onlay Buccal Mucosa Graft Urethroplasty in Patients after
Radiotherapy.
AB - PURPOSE: We evaluated stricture-free survival and functional outcomes of buccal
mucosa graft urethroplasty in patients with urethral stricture disease after
radiotherapy. MATERIALS AND METHODS: We reviewed our urethroplasty database for
patients with a radiotherapy history who underwent buccal mucosa graft
urethroplasty between January 2009 and October 2013. We reviewed patient charts
and the institutional, standardized, nonvalidated questionnaires administered to
each patient postoperatively. Study end points included 1) the success rate, 2)
continence status, 3) erectile function and 4) patient satisfaction
postoperatively. Success was defined as stricture-free survival. RESULTS: Of 38
men included in the study prostate cancer was the most common indication for
radiotherapy in 35 (92.1%). External beam radiotherapy was performed in 24 cases
(64.9%), brachytherapy was done in 8 (21.6%) and a combination of the 2
treatments was performed in 6 (13.5%). Strictures were in the
bulbar/bulbomembranous urethra and had a median length of 3.0 cm (range 1.0 to
8.0). The overall success rate was 71.1% at a median followup of 26.5 months
(range 1.0 to 50.0). Median time to stricture recurrence was 17.0 months (range
3.0 to 44.0). De novo urinary incontinence was observed in 4 patients (10.5%).
Erectile function remained mostly unchanged compared to preoperative status.
Study limitations include the small sample size and the lack of validated
questionnaires. CONCLUSIONS: At short-term to mid-term followup the success rate
of ventral onlay buccal mucosa graft urethroplasty in patients with radiotherapy
history seems acceptable. However, patients must be counseled about the increased
risk of urinary incontinence. Longer followup is warranted to address long-term
outcomes.
PMID- 25846418
TI - Disparities in the Use of Sacral Neuromodulation among Medicare Beneficiaries.
AB - PURPOSE: Sacral neuromodulation with the InterStim(r) has been done to treat
urinary and bowel control. There are limited data in the literature on use trends
of sacral neuromodulation. We explored disparities in use among Medicare
beneficiaries. MATERIALS AND METHODS: We queried a 5% national random sample of
Medicare claims for 2001, 2004, 2007 and 2010. All patients with an ICD-9
diagnosis code representing a potential urological indication for sacral
neuromodulation were included. Patients who underwent device implantation were
identified using CPT-4 codes. Statistical analysis was done with the chi-square
and Fisher tests, and multivariate logistic regression using software. RESULTS: A
total of 2,322,060 patients were identified with a diagnosis that could
potentially be treated with sacral neuromodulation. During the 10-year study
period the percent of these patients who ultimately underwent implantation
increased from 0.03% to 0.91% (p <0.0001) for a total of 13,360 (0.58%). On
logistic regression analysis women (OR 3.85, p <0.0001) and patients younger than
65 years (OR 1.00 vs 0.29 to 0.39, p <0.0001) were more likely to be treated.
Minority patients (OR 0.38, p <0.0001) and those living in the western United
States (OR 0.52, p <0.0001) were less likely to receive treatment. CONCLUSIONS:
Sacral neuromodulation use significantly increased among Medicare beneficiaries
in a 10-year period. Patients were more likely to be treated with sacral
neuromodulation if they were female, white, younger (younger than 65 years) and
living outside the western United States.
PMID- 25846419
TI - Lamin A/C Acts as an Essential Factor in Mesenchymal Stem Cell Differentiation
Through the Regulation of the Dynamics of the Wnt/beta-Catenin Pathway.
AB - Changes in the expression of lamin A/C, a fibrilar protein of the nuclear
envelope, are associated with the cellular features of age-related bone loss.
Reduced expression of lamin A/C inhibits osteoblastogenesis while facilitating
adipogenic differentiation of mesenchymal stem cells (MSC) in vitro and in vivo.
In this study we investigated the regulatory role that lamin A/C plays on the
essential elements of the Wnt/beta-catenin pathway, which are pivotal in MSC
differentiation. Initially, we assessed the effect of lamin A/C gene (LMNA)
overexpression on MSC differentiation while compared it to lamin A/C depleted
MSC. Osteogenesis and gene expression of osteogenic factors were higher in LMNA
transfected MSC as compared to control. Conversely, adipogenesis and expression
of adipogenic factors were significantly lower in LMNA transfected cells. Nuclear
beta-catenin was significantly higher (~two fold) in MSC expressing higher levels
of LMNA as compared to control with nuclear beta-catenin levels being
significantly lower (~ -42%) in siRNA-treated MSC. Luciferase activity for beta
catenin-mediated transcriptional activation was significantly higher in cells
overexpressing LMNA. These data indicate that MSC overexpressing LMNA have higher
osteogenic and lower adipogenic differentiation potential. In conclusion, our
studies demonstrate that lamin A/C plays a significant role in the
differentiation of both osteoblasts and adipocytes by regulating some of the
elements of Wnt/beta-catenin signaling during early MSC differentiation.
PMID- 25846420
TI - The cost of errors: Perceived error detection in dual-task conditions.
AB - Detecting that an error has been made can be crucial for the implementation of
appropriate behavioral adjustments. Brain imaging studies indicate that error
detection is not limited to response errors and that similar mechanisms are
engaged even when behavioral control is not needed. The current study examines
whether perceived error detection - the detection of erroneous stimuli that
violate our expectations - requires central resources. In two experiments - using
a dual-task design - we show that perceived error detection in the first task
creates a bottleneck in information processing and delays the response selection
of the second task. The results suggest that the requirement for central
cognitive resources is a general feature of error detection because it is present
even when the demand for behavioral control is low.
PMID- 25846422
TI - Accumulation of cell-penetrating peptides in large unilamellar vesicles: A
straightforward screening assay for investigating the internalization mechanism.
AB - The internalization of cell-penetrating peptides (CPPs) into liposomes (large
unilamellar vesicles, LUVs) was studied with a rapid and robust procedure based
on the quenching of a small fluorescent probe, 7-nitrobenz-2-oxa-1,3-diazole
(NBD). Quenching can be achieved by reduction with dithionite or by pH jump. LUVs
with different compositions of phospholipids (PLs) were used to screen the
efficacy of different CPPs. In order to "validate" the composition of the
membrane models, a control cationic peptide, which does not enter eukaryotic
cells, was included in the study. It was found that pure DOPG or DOPG within
ternary mixtures with cholesterol are the most appropriate models for studying
CPP translocation. An anionic lipid, such as DOPG, is required for the adsorption
of the basic peptides on the surface of LUVs. In addition, it acts as transfer
agent through the lipid bilayer. A fluid phase and/or the presence of phase
defects also appear mandatory for the internalization to occur. The
neutralization of charges within an inverted micelle demonstrated in the case of
DOPG and also proposed for a ternary mixture of PLs might not be the only
mechanism for the CPP translocation. Finally, it is shown that oleic acid
facilitates the entry inside LUVs in gel phase of a series of cationic peptides
including CPPs and also the negative control peptide PKCi.
PMID- 25846421
TI - Lymph node status in inflammatory breast cancer.
AB - Positive lymph node status in breast cancer is known to be an adverse prognostic
factor, but the effect of lymph node (LN) status in inflammatory breast cancer
(IBC) has not been evaluated. This study was designed to investigate the
association between lymph node status and overall survival (OS) in individuals
with IBC. Using the Surveillance, Epidemiology, and End Results (SEER) 18
registry, we collected data on 761 patients diagnosed with non-metastatic IBC
from 2004 to 2008. Survival analysis was performed using the Kaplan-Meier method.
Cox proportional hazard regression was performed to evaluate univariate and
multivariate associations between estrogen and progesterone receptor (ER/PR)
status, treatment, and OS. Positive nodal status was associated with a
significant decrease in OS (p < 0.001). Five-year survival for LN-positive and LN
negative patients was 49 and 66 %, respectively. In node-positive patients, ER or
PR positivity was associated with improved OS, (p = 0.025, p = 0.007). In node
positive patients, the combination of surgery and radiation therapy improved OS
when compared with surgery alone (p = 0.002). Nearly 80 % of the patients in this
study had nodal metastasis. Positive nodal status was found to be an adverse
prognostic factor. ER/PR positivity and treatment with surgery and radiation in
node-positive patients was found to improve outcomes. Further studies are
required to characterize the biology of IBC and guide the optimal treatment of
this disease.
PMID- 25846426
TI - Is drug insurance status an effect modifier in epidemiologic database studies?
The case of maternal asthma and major congenital malformations.
AB - BACKGROUND: Our previous work on the association between maternal asthma and
congenital malformations was based on cohorts formed by women with public drug
insurance, i.e., over-represented by women with lower socioeconomic status,
questioning the generalizability of our findings. This study aimed to evaluate
whether or not drug insurance status, as a proxy of socioeconomic status, is an
effect modifier for the association between maternal asthma and major congenital
malformations. METHODS: A cohort of 36,587 pregnancies from asthmatic women and
198,935 pregnancies from nonasthmatic women selected independently of their drug
insurance status was reconstructed with Quebec administrative databases (1998
2009). Asthmatic women were identified using a validated case definition of
asthma. Cases of major congenital malformations were identified using diagnostic
codes recorded in the hospitalization database. Drug insurance status at the
beginning of pregnancy was classified into three groups: publicly insured with
social welfare, publicly insured without social welfare, and privately insured.
Adjusted odds ratios were estimated with generalized estimation equations,
including an interaction term between maternal asthma and drug insurance status.
RESULTS: The prevalence of congenital malformations was 6.8% among asthmatic
women and 5.8% among nonasthmatics. The impact of asthma on the prevalence of
congenital malformations was significantly greater in women publicly insured with
social welfare (odds ratio = 1.42; 95% confidence interval, 1.25-1.61) than in
the other two groups ([odds ratio = 1.10; 1.00-1.21] in the publicly insured
without social welfare and [odds ratio = 1.13; 1.07-1.20] in the privately
insured group). CONCLUSION: The increased risk of major congenital malformation
associated with asthma was significantly higher among pregnant women publicly
insured with social welfare than among those privately insured. As a result of
this effect modification by drug insurance status, findings from Quebec
observational studies using databases mainly formed of patients publicly insured
with social welfare may not be generalized to the entire population.
PMID- 25846425
TI - Downregulation of inhibitor of apoptosis-stimulating protein of p53 inhibits
proliferation and promotes apoptosis of gastric cancer cells.
AB - Gastric cancer (GC) remains one of the leading causes of cancer-associated
mortality. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a member
of the inhibitory apoptosis-stimulating protein p53 family. The overexpression of
iASPP has been detected in several types of tumor in humans. However, the role of
iASPP in GC remains to be elucidated. The objectives of the present study were to
detect the expression of iASPP in GC and examine the potential role of iASPP in
GC cell lines. Using reverse transcription-quantitative polymerase chain reaction
and western blot analyses, it was identified that the expression of iASPP in GC
tissues and GC cell lines was higher compared with that in adjacent normal
tissues and in a normal gastric mucosa cell line (GES-1). To examine the role of
iASPP in GC cells, the expression of iASPP was inhibited using a small
interfering (si)RNA against iASPP and it was observed that iASPP expression was
significantly downregulated. Using MTT assays, colony-formation assays and flow
cytometry, it was identified that the inhibition of iASPP was able to
significantly inhibit the proliferation and colony forming ability and promote
apoptosis in GC cells. To examine the role of iASPP in GC cells in vivo, GC
cells, which were infected with iASPP-siRNA or control-siRNA were subcutaneously
injected into nude mice. It was identified that downregulation of iASPP
significantly inhibited tumor growth in vivo. Thus, iASPP may be a potential
molecular target in GC therapy.
PMID- 25846427
TI - NRF2/KEAP1 and Wnt/beta-catenin in the multistep process of liver carcinogenesis
in humans and rats.
PMID- 25846433
TI - Posaconazole liquid suspension in solid organ transplant recipients previously
treated with voriconazole.
AB - BACKGROUND: Posaconazole (PCZ) has become an attractive alternative to
voriconazole (VCZ) in transplant recipients with suspected or proven invasive
filamentous fungal infections, causing fewer drug interactions. Here, we describe
our experience with PCZ after VCZ in solid organ transplant (SOT) recipients.
METHODS: VCZ was replaced by PCZ liquid solution in 19 SOT recipients (15 lung, 2
kidney, 1 liver, and 1 heart/lung) with invasive pulmonary aspergillosis (12/19;
63.2%), possible invasive pulmonary fungal infection (2/19; 10.5%), prophylaxis
(2/19; 10.5%), or pulmonary scedosporiosis, mucormycosis, and mixed fungal
species (1 each). Rationales for switch were suspected adverse reactions to VCZ
(17/19; 89.4%) and desire to broaden spectrum of coverage to include agents of
mucormycosis (3/19; 15.8%). RESULTS: PCZ was well tolerated in all patients. In
those patients with baseline liver enzyme abnormalities, a median change occurred
in concentrations of alanine transaminase (-20 IU/L), aspartate aminotransferase
(-17.5 IU/L), and alkaline phosphatase (-61.5 IU/L). Clinical success
(resolution, stabilization, or prevention of infection) was achieved in 16/19
(84%) people. CONCLUSION: PCZ appears to have a reasonable safety and
tolerability profile and may be an effective alternative in SOT patients who
require an agent with anti-mold activity, but are unable to tolerate VCZ.
PMID- 25846434
TI - Sucrose-induced analgesia during early life modulates adulthood learning and
memory formation.
AB - This study is aimed at examining the long-term effects of chronic pain during
early life (postnatal day 0 to 8weeks), and intervention using sucrose, on
cognitive functions during adulthood in rats. Pain was induced in rat pups via
needle pricks of the paws. Sucrose solution or paracetamol was administered for
analgesia before the paw prick. Control groups include tactile stimulation to
account for handling and touching the paws, and sucrose alone was used. All
treatments were started on day one of birth and continued for 8weeks. At the end
of the treatments, behavioral studies were conducted to test the spatial learning
and memory using radial arm water maze (RAWM), as well as pain threshold via foot
withdrawal response to a hot plate apparatus. Additionally, the hippocampus was
dissected, and blood was collected. Levels of neurotrophins (BDNF, IGF-1 and NT
3) and endorphins were assessed using ELISA. The results show that chronic
noxious stimulation resulted in comparable foot-withdrawal latency between
noxious and tactile groups. On the other hand, pretreatment with sucrose or
paracetamol increased pain threshold significantly both in naive rats and
noxiously stimulated rats (P<0.05). Chronic pain during early life impaired short
term memory, and sucrose treatment prevented such impairment (P<0.05). Sucrose
significantly increased serum levels of endorphin and enkephalin. Chronic pain
decreased levels of BDNF in the hippocampus and this decrease was prevented by
sucrose and paracetamol treatments. Hippocampal levels of NT-3 and IGF-1 were not
affected by any treatment. In conclusion, chronic pain induction during early
life induced short memory impairment, and pretreatment with sucrose prevented
this impairment via mechanisms that seem to involve BDNF. As evident in the
results, sucrose, whether alone or in the presence of pre-noxious stimulation,
increases pain threshold in such circumstances; most likely via a mechanism that
involves an increase in endogenous opioids.
PMID- 25846435
TI - Male song quality modulates c-Fos expression in the auditory forebrain of the
female canary.
AB - In canaries, specific phrases of male song (sexy songs, SS) that are difficult to
produce are especially attractive for females. Females exposed to SS produce more
copulation displays and deposit more testosterone into their eggs than females
exposed to non-sexy songs (NS). Increased expression of the immediate early genes
c-Fos or zenk (a.k.a. egr-1) has been observed in the auditory forebrain of
female songbirds hearing attractive songs. C-Fos immunoreactive (Fos-ir) cell
numbers were quantified here in the brain of female canaries that had been
collected 30min after they had been exposed for 60min to the playback of SS or NS
or control white noise. Fos-ir cell numbers increased in the caudomedial
mesopallium (CMM) and caudomedial nidopallium (NCM) of SS birds as compared to
controls. Song playback (pooled SS and NS) also tended to increase average Fos-ir
cell numbers in the mediobasal hypothalamus (MBH) but this effect did not reach
full statistical significance. At the individual level, Fos expression in CMM was
correlated with its expression in NCM and in MBH but also with the frequency of
calls that females produced in response to the playbacks. These data thus
indicate that male songs of different qualities induce a differential metabolic
activation of NCM and CMM. The correlation between activation of auditory regions
and of the MBH might reflect the link between auditory stimulation and changes in
behavior and reproductive physiology.
PMID- 25846436
TI - Effect of pentobarbital and isoflurane on acute stress response in rat.
AB - BACKGROUND: Anesthesia administration before sacrificing animals is a common
practice in stress-related studies, but the effect of anesthesia on the results
remains understudied. We aimed to reveal the interference of different
anesthetics, i.e. intraperitoneal (i.p.) sodium-pentobarbital injection or
isoflurane inhalation, with the acute stress responses in rats. METHODS: Rats
were randomly divided into foot shock (FS) and non-stressed control groups, and
further grouped according to the sacrificing procedure: direct decapitation,
decapitation after i.p. sodium-pentobarbital injection, or isoflurane inhalation.
There was also a non-stressed group sacrificed by decapitation following i.p.
saline injection. Plasma levels of corticosterone (CORT), testosterone and
estradiol, hypothalamic stress-related molecule mRNA expression of corticotropin
releasing hormone, arginine vasopressin and oxytocin, and frontal lobe stress
related molecule mRNA expression of NMDA receptor subunit NR2B, GABAA receptor
and the neuronal-type nicotinic acetylcholine receptor were measured. RESULTS: FS
significantly increased plasma CORT levels in direct decapitation and isoflurane
groups, while this stress response 'disappeared' following i.p. sodium
pentobarbital injection. In control animals, both the injection of saline and
pentobarbital caused a significant increase of plasma CORT. Neither the sex
hormone levels nor the mRNA expression of stress-related molecules in the brain
showed significant differences among the groups. CONCLUSION: The injection of the
anesthetic compound rather than the compound itself may cause extra stress which
interferes with the plasma CORT levels, but not with plasma sex hormone levels
nor with the brain mRNA expression. Isoflurane inhalation leaves the stress
response intact and is also optimal from an ethical point of view.
PMID- 25846437
TI - Development and validation of a tool incorporating cervical length and
quantitative fetal fibronectin to predict spontaneous preterm birth in
asymptomatic high-risk women.
AB - OBJECTIVE: To develop a predictive tool for spontaneous preterm birth (sPTB) in
asymptomatic high-risk women that includes quantification of fetal fibronectin
(fFN) along with cervical length (CL) measurement and other clinical factors.
METHODS: Data were analyzed that had been collected prospectively from 1249 women
at high risk for sPTB attending preterm surveillance clinics. Clinicians were
blinded to quantitative measurements of fFN (qfFN), although they were aware of
qualitative fFN results. Parametric survival models for sPTB, with time-updated
covariates, were developed and the best was selected using the Akaike and
Bayesian information criteria. The model was developed on the first 624
consecutive women and validated on the subsequent 625. Fractional polynomials
were used to accommodate possible non-linear effects of qfFN and CL. The
estimated probability of delivery before 30, 34 or 37 weeks' gestation and within
2 or 4 weeks of testing was calculated for each patient and analyzed as a
predictive test for the actual occurrence of each event. Predictive statistics
were calculated to compare training and validation sets. RESULTS: The final model
that was selected used a log-normal survival curve with CL, ?qfFN and previous
sPTB/preterm prelabor rupture of membranes as predictors. Predictive statistics
were similar for training and validation sets. Areas under the receiver-operating
characteristics curves ranged from 0.77 to 0.99, indicating accurate prediction
across all five delivery outcomes. CONCLUSIONS: sPTB in high-risk asymptomatic
women can be predicted accurately using a model combining qfFN and CL, which
supersedes the single-threshold fFN test, demographic information and obstetric
history. This algorithm has been incorporated into an App (QUiPP) for widespread
use.
PMID- 25846438
TI - [Central nervous system vasculitis according to the 2012 revise international
Chapel Hill consensus conference nomenclature of vasculitides].
AB - Vasculitis can be primarily or secondarily to various underlying diseases. It
frequently affects the nervous system, and neurological deficits may remain even
after disease remission. Because the progression of vasculitides is usually acute
to subacute, early initiation of treatment is important from the viewpoint of
patients' functional status. However, early diagnosis may be difficult,
particularly in patients with central nervous system vasculitis. Hence, it is
important to understand the wide-ranging clinical manifestations of vasculitides.
Here, we summarize the 2012 revised International Chapel Hill Consensus
Conference nomenclature of vasculitides from the standpoint of central nervous
system vasculitis.
PMID- 25846439
TI - [Diagnostic imaging of central nervous system vasculitis].
AB - Vasculitis involving the central nervous system presents with infarction and
hemorrhage, which are often nonspecific findings. Laboratory examinations are
essential for diagnosis of vasculitis in addition to comprehensive and systematic
review of the clinical course. Although most findings tend to be nonspecific,
enhancement and thickening of the vascular wall indicate vasculitis.
Visualization of the vascular wall requires selection of the appropriate imaging
modality and mode of image acquisition. Contrast-enhanced CT, MRI, and FDG-PET
are useful for visualizing large vessel vasculitis, while CT, MRI, and
angiography are effective for medium vessel vasculitis. The use of ultrasound is
limited to evaluating vessels on the body surface. Although relatively thick
vessels can be demonstrated by angiography, complete survey of small vessels is
difficult. Here, we summarize the characteristics of each imaging modality and
imaging findings of typical vasculitides-Takayasu arteritis, giant cell
arteritis, ANCA-associated vasculitis, Behcet's disease, primary angiitis of the
CNS, and vasculitis associated with systemic disease. Differential diagnoses are
also shown, including infective endocarditis, tuberculous meningitis, Ehlers
Danlos syndrome, and reversible cerebral vasoconstriction syndrome.
PMID- 25846440
TI - [Angiitis of the autonomic central nervous system].
AB - Autonomic central nervous system (CNS) angiitis was classified with primary
angiitis of the CNS (PACNS) or CNS angiitis secondary to systemic vasculitis.
Mean onset age of PACNS was about 50 years. Typical symptoms were a chronic
progressive headache and encephalopathy. Cerebrospinal fluid analysis was
compatible with aseptic meningitis. Findings from imaging were varied and
included arterial stenosis. Exclusion diagnosis of PACNS mimics and a brain
biopsy were required for a definite diagnosis. Some collagen diseases could cause
secondary CNS vasculitis. Patients with secondary CNS vasculitis were required
more extensive immunosuppression therapy.
PMID- 25846441
TI - [Central nervous system Vasculitis due to infectious diseases].
AB - Varicella zoster virus may cause vasculitis or vasculopathy, and positive
polymerase chain reactions for varicella zoster virus deoxyribonucleic acid in
the cerebrospinal fluid and/or the intrathecal synthesis of antibodies to the
varicella zoster virus suggest these diagnoses. Meningovascular syphilis may
involve the middle cerebral artery and basilar artery and may cause a stroke.
Aspergillus is vasoinvasive and may cause hemorrhagic infarction by forming an
intravascular thrombus.
PMID- 25846442
TI - [Inflammatory cerebral amyloid angiopathy].
AB - Inflammatory cerebral amyloid angiopathy (CAA) typically affects older patients
who present with acute or subacute cognitive decline, headache, behavioral
change, seizures, and focal neurological deficits. Brain magnetic resonance
imaging (MRI) reveals patchy or confluent asymmetric white matter
hyperintensities on T2-weighted or fluid-attenuated inversion recovery images,
which indicates vasogenic edema, and previous lobar hemorrhages and/or multiple
lobar microbleeds on T2*-weighted gradient-recalled echo or
susceptibility-weighted imaging. Neuropathological findings include frank
vasculitis and/or perivascular inflammation with mononuclear or multinucleated
giant cells that are associated with amyloid-beta (Abeta)-laden vessels.
Importantly, these findings suggest that these patients may respond well to
immunosuppressive treatment with high-dose corticosteroids and/or
cyclophosphamide. The pathogenesis of this syndrome is still unknown, although
anti-Abeta autoantibodies in the cerebrospinal fluid may mediate inflammatory
processes against cerebrovascular Abeta. Moreover, MRI findings in patients with
inflammatory CAA are very similar to those in patients with Alzheimer's disease
who were treated with a monoclonal anti-Abeta antibody, and these findings are
called amyloid-related imaging abnormalities (ARIA). Anti-Abeta autoantibodies in
the cerebrospinal fluid might be a biomarker of future disease-modifying
therapies for patients with Alzheimer's disease and CAA.
PMID- 25846443
TI - [Treatment for central nervous system vasculitis].
AB - Central nervous system (CNS) vasculitis is classified into two categories based
on whether it is primary or secondary. Primary CNS vasculitis is rare disorder of
unknown cause that is restricted to the brain and spinal cord. Currently, there
are no randomized clinical trials for treatment of primary CNS vasculitis.
Therefore, treatment regimens for primary CNS vasculitis have been derived from
therapeutic strategies used in other kinds of vasculitis. Early detection is
important because corticosteroid treatment with or without cyclophosphamide can
often prevent serious outcomes and may result in a favorable response. However,
because some patients are intolerant or respond poorly to combination therapy,
development of novel treatment options is eagerly awaited. Several
immunosuppressive agents such as mycophenolate mofetil, tumor necrosis factor
alpha blockers, and rituximab could be options for refractory patients.
PMID- 25846444
TI - [Mental time dysfunction in Parkinson's and Alzheimer's diseases].
AB - Mental time is altered by a number of factors and the underlying neural
processing involved is highly complicated. Recent research suggests that mental
time in patients with particular neurological diseases is perceptually shorter
than in normal individuals. This review introduces mental time dysfunction and a
model for processing of mental time in Parkinson's and Alzheimer's disease.
Although the two diseases show the same dysfunction of mental time in behavior,
we expect the underlying neural mechanism to vary in each disease. It is possible
that the dysfunction of mental time in Parkinson's disease is caused by the
abnormal striatum acting as a pacemaker, while that in Alzheimer's disease is
caused by abnormal hippocampal memory.
PMID- 25846445
TI - [Three neural networks that support syntactic processing in language].
AB - Elucidation of language disorders is one of the fundamental issues in clinical
neuroscience. We used magnetic resonance imaging and a syntactic task in Japanese
to examine the behavior and brain structures of patients with a left frontal
glioma. We successfully showed that they had different types of language
disorders (particularly agrammatic comprehension) dependent on the location of
the glioma. Moreover, we describe three neural networks that support syntactic
processing, including an extensive network within the cerebellum and both
hemispheres of the brain.
PMID- 25846446
TI - [A case with apraxia of tool use: selective inability to form a hand posture for
a tool].
AB - Impaired tool use is recognized as a symptom of ideational apraxia. While many
studies have focused on difficulties in producing gestures as a whole, using
tools involves several steps; these include forming hand postures appropriate for
the use of certain tool, selecting objects or body parts to act on, and producing
gestures. In previously reported cases, both producing and recognizing hand
postures were impaired. Here we report the first case showing a selective
impairment of forming hand postures appropriate for tools with preserved
recognition of the required hand postures. A 24-year-old, right-handed man was
admitted to hospital because of sensory impairment of the right side of the body,
mild aphasia, and impaired tool use due to left parietal subcortical hemorrhage.
His ability to make symbolic gestures, copy finger postures, and orient his hand
to pass a slit was well preserved. Semantic knowledge for tools and hand postures
was also intact. He could flawlessly select the correct hand postures in
recognition tasks. He only demonstrated difficulties in forming a hand posture
appropriate for a tool. Once he properly grasped a tool by trial and error, he
could use it without hesitation. These observations suggest that each step of
tool use should be thoroughly examined in patients with ideational apraxia.
PMID- 25846447
TI - [A case of Wernicke's encephalopathy with detrusor-sphincter dyssynergia].
AB - We report a case of a 54-year-old man with alcoholic Wernicke's encephalopathy.
Neurological examination showed unconsciousness, absence of the oculocephalic
reflex, generalized hyporeflexia, and urinary retention. The patient immediately
regained consciousness after the administration of thiamine, but amnesia and
cerebellar ataxia became apparent. The urinary retention persisted, and an
urodynamic study showed detrusor-sphincter dyssynergia. Three months after the
treatment, the urinary retention resolved, and a second urodynamic study showed
disappearance of the detrusor-sphincter dyssynergia. Wernicke's encephalopathy
involves the periaqueductal gray matter and the floor of the fourth ventricle.
For the voiding reflex, the periaqueductal gray matter neurons project to the
pontine micturition center, which seems to be located adjacent to the locus
coeruleus. We concluded that lesions of the periaqueductal gray matter and/or the
dorsolateral portion of the pons were responsible for the micturitional
disturbance in the patient.
PMID- 25846448
TI - [A case of representational dysgraphia and object representational disorder with
unilateral spatial neglect].
AB - We describe the case of a 48-year-old left-handed woman with unilateral neglect
from a brain infarction in the area of the right basal ganglia and temporo
parieto-occipital lobe. When a Kanji character was dictated to her, she wrote
only the right side (tukuri) of the character. When copying a picture from the
visual image of a left-right asymmetrical object, such as the side view of the
dog, she drew the tail and a hind leg immediately but was unable to draw a
picture of the dog from the left side. We asked her to imagine going around to
the opposite side of the imaginary dog and to draw it from that perspective. She
easily drew the left side first, resulting in a left-right inverted picture of
what she had previously drawn. She then tried to slowly visualize the missing
part of her imagery, and was able to draw only the right tip of the missing part.
She could not compose a complete picture of the dog. These findings suggested
that the impairment was in the imaging of the left side of a character or object
and that this was a case of representational dysgraphia and object
representational disorder with unilateral spatial neglect.
PMID- 25846449
TI - A product of RpfB and RipA joint enzymatic action promotes the resuscitation of
dormant mycobacteria.
AB - Resuscitation-promoting factor proteins (Rpfs) are known to participate in
reactivating the dormant forms of actinobacteria. Structural analysis of the Rpf
catalytic domain demonstrates its similarity to lysozyme and to lytic
transglycosylases - the groups of enzymes that cleave the beta-1,4-glycosidic
bond between N-acetylmuramic acid (MurNAc) and GlcNAc, and concomitantly form a
1,6-anhydro ring at the MurNAc residue. Analysis of the products formed from
mycobacterial peptidoglycan hydrolysis reactions containing a mixture of RpfB and
resuscitation-promoting factor interacting protein (RipA) allowed us to identify
the suggested product of their action - N-acetylglucosaminyl-beta(1 -> 4)-N
glycolyl-1,6-anhydromuramyl-L-alanyl-D-isoglutamate. To identify the role of this
resulting product in resuscitation, we used a synthetic 1,6-anhydrodisaccharide
dipeptide, and tested its ability to stimulate resuscitation by using the dormant
Mycobacterium smegmatis model. It was found that the disaccharide-dipeptide was
the minimal structure capable of resuscitating the dormant mycobacterial cells
over the concentration range of 9-100 ng . mL(-1). The current study therefore
provides the first insights into the molecular mechanism of resuscitation from
dormancy involving a product of RpfB/RipA-mediated peptidoglycan cleavage.
PMID- 25846450
TI - Is it time to target gut dysbiosis and immune dysfunction in the therapy of
hepatic encephalopathy?
AB - The development of overt hepatic encephalopathy (HE) in a patient with cirrhosis
confers a damning prognosis with a 1-year mortality approaching 64%. This complex
neuropsychiatric syndrome arises as a consequence of a dysfunctional gut-liver
brain axis. HE has been largely neglected over the past 30 years, with the
reliance on therapies aimed at lowering ammonia production or increasing
metabolism following the seminal observation that the hepatic urea cycle is the
major mammalian ammonia detoxification pathway and is key in the pathogenesis of
HE. The relationship with ammonia is more clear-cut in acute liver failure; but
in cirrhosis, it has become apparent that inflammation is a key driver and that a
disrupted microbiome resulting in gut dysbiosis, bacterial overgrowth and
translocation, systemic endotoxemia and immune dysfunction may be more important
drivers. Therefore, it is important to re-focus our efforts into developing
therapies that modulate the disrupted microbiome or alleviating its downstream
consequences.
PMID- 25846451
TI - Modifications to the frailty phenotype criteria: Systematic review of the current
literature and investigation of 262 frailty phenotypes in the Survey of Health,
Ageing, and Retirement in Europe.
AB - We conducted a systematic review to determine variability in how the criteria of
the frailty phenotype (grip strength, weight loss, exhaustion, walking speed,
physical activity) were assessed. We then evaluated the impact on estimating
prevalence and mortality of modifying the criteria, using the Survey of Health,
Ageing, & Retirement in Europe (SHARE). Five databases were searched for original
research articles published after 2000, which evaluated frailty using the
phenotypic criteria. Among the 264 included studies, 24 studies provided enough
information to demonstrate that all criteria were assessed as proposed in the
original frailty phenotype study by Fried et al. (2001). Physical inactivity and
weight loss were the criteria most often modified. We then created 262 phenotypes
from SHARE based on common modifications found in the review. Among these
phenotypes, frailty prevalence ranged from 12.7% to 28.2%. Agreement with the
primary frailty phenotype ranged from 0.662 to 0.967 and internal consistency
ranged from 0.430 to 0.649. Women had 2.1-16.3% higher frailty prevalence than
men. Areas under receiver operating characteristic curves for discriminating five
year mortality ranged from 0.607 (95% CI: 0.583-0.630) to 0.668 (0.645-0.691).
The frailty phenotype often has been modified, and these modifications have
important impact on its classification and predictive ability.
PMID- 25846452
TI - Dominant hand operating probe vs needle: a comparison study of ultrasound-guided
needle placement in phantom models.
AB - We conducted a replicated crossover design study to assess if using one's
dominant hand for operating a probe vs directing a needle would affect the time
taken, the number of needle passes and the accuracy of an ultrasound-guided
procedure in phantom models. Twenty ultrasound-novice participants completed the
task 10 times for each hand arrangement (alternating between attempts). The time
taken and number of needle passes required for both dominant hand-probe and hand
needle decreased over time (p = 0.001). Dominant hand-needle had a lower mean
time used (p = 0.001) and fewer needle passes (p = 0.02) compared with hand
probe. Sixty-five per cent of participants preferred using their dominant hand to
direct the needle. When learning ultrasound-guided needle procedures on phantom
models, use of the dominant hand to operate the needle is associated with a
shorter procedure time and fewer needle passes.
PMID- 25846453
TI - Presumptive congenital radial head sub-luxation in a shih tzu: successful
management by radial head ostectomy.
AB - Congenital radial head sub-luxation was diagnosed in a 7-month-old, neutered male
shih tzu that presented with a limb deformity and severe lameness of the right
fore limb. Radiography revealed a craniolateral sub-luxation of the right radial
head, which was treated by radial head ostectomy, fixation of the radius to the
ulna with a screw and joint stabilisation with suture-anchors and cerclage wire.
Surgical treatment followed by physiotherapy resulted in a fully functional, well
aligned and non-painful elbow. To the authors' knowledge this is the first case
report of a congenital radial head sub-luxation in a craniolateral direction in a
dog and also one successfully managed with radial head ostectomy and radioulnar
synostosis.
PMID- 25846454
TI - Studies on the development of 169Yb-brachytherapy seeds: New generation
brachytherapy sources for the management of cancer.
AB - This paper describes development of (169)Yb-seeds by encapsulating 0.6-0.65 mm
(phi) sized (169)Yb2O3 microspheres in titanium capsules. Microspheres
synthesized by a sol-gel route were characterized by XRD, SEM/EDS and ICP-AES.
Optimization of neutron irradiation was accomplished and (169)Yb-seeds up to 74
MBq of (169)Yb could be produced from natural Yb2O3 microspheres, which have the
potential for use in prostate brachytherapy. A protocol to prepare (169)Yb
brachytherapy sources (2.96-3.7 TBq of (169)Yb) with the use of enriched targets
was also formulated.
PMID- 25846455
TI - Seabed radioactivity based on in situ measurements and Monte Carlo simulations.
AB - Activity concentration measurements were carried out on the seabed, by
implementing the underwater detection system KATERINA. The efficiency calibration
was performed in the energy range 350-2600 keV, using in situ and laboratory
measurements. The efficiency results were reproduced and extended in a broadened
range of energies from 150 to 2600 keV, by Monte Carlo simulations, using the
MCNP5 code. The concentrations of (40)K, (214)Bi and (208)Tl were determined
utilizing the present approach. The results were validated by laboratory
measurements.
PMID- 25846456
TI - Profiling of actionable gene alterations in ovarian cancer by targeted deep
sequencing.
AB - To construct a profile of therapeutically actionable gene alterations in the
major histological types of ovarian cancer, 72 Japanese patients with surgically
resected ovarian cancers were selected from an original cohort consisting of 267
patients who had not received pre-treatment before surgery. Somatic mutations and
copy number alterations at 740 hotspots in 46 cancer-related genes were detected
by deep sequencing of genomic DNAs obtained from snap-frozen tumor tissues using
a next generation sequencer. The alterations were verified by Sanger sequencing
and quantitative genomic PCR. Mutations and/or copy number aberrations which will
make tumors respond to molecular targeting drugs were detected in nine genes of
35/72 (48.6%) patients; PIK3CA (25.0%), KRAS (13.9%), ERBB2 (4.3%), PTEN (2.8%),
RB1 (2.8%), CDKN2A (2.8%), AKT1 (1.4%), CTNNB1 (1.4%) and NRAS (1.4%). These
mutations tended to occur in a mutually exclusive manner. Non-serous histological
type tumors showed such actionable gene alterations frequently (32/47; 68.1%).
Therefore, ovarian cancers, particularly of non-serous types, frequently carry
gene aberrations that link to therapy using molecular targeting drugs.
PMID- 25846457
TI - Exome sequencing identifies a homozygous C5orf42 variant in a Turkish kindred
with oral-facial-digital syndrome type VI.
AB - Oral-facial-digital syndrome type VI (OFDVI) is a rare ciliopathy in the spectrum
of Joubert syndrome (JS) and distinguished from other oral-facial-digital
syndromes by metacarpal abnormalities with central polydactyly and by a molar
tooth sign on cranial MRI. Additional characteristic features include short
stature, micrognathia, posteriorly rotated low-set ears, hypertelorism,
epicanthal folds, broad nasal tip, tongue hamartoma, upper lip notch, intraoral
frenula, cleft lip/palate, and renal anomalies. Recently, novel mutations in
C5orf42 were identified in 9 out of 11 OFDVI families. In a subsequent study
C5orf42 was found to be mutated in only 2 out of 17 OFDVI probands while 28
patients with a pure JS phenotype also had pathogenic mutations of C5orf42. We
report on two affected cousins diagnosed with OFDVI who were born from first
degree cousin marriages. Whole exome sequencing (WES) identified a homozygous
predicted damaging missense mutation (c.4034A > G; p.Gln1345Arg) in the C5orf42
gene. Our data contribute to the evidence that C5orf42 is one of the causative
genes for OFDVI.
PMID- 25846458
TI - Acute pediatric encephalitis neuroimaging: single-institution series as part of
the California encephalitis project.
AB - PURPOSE: Diagnosing pediatric encephalitis is challenging because of varied
clinical presentation, nonspecific neuroimaging features, and rare confirmation
of causality. We reviewed acute neuroimaging of children with clinically
suspected encephalitis to identify findings that may correlate with etiology and
length of stay. METHODS: Imaging of 141 children with clinically suspected
encephalitis as part of The California Encephalitis Project from 2005 to 2012 at
a single institution was reviewed to compare the extent of neuroimaging
abnormalities to patient age, gender, length of stay, and unknown, possible, or
confirmed pathogen. Scan review was blinded and categorized by extent and
distribution of abnormal findings. RESULTS: Abnormal findings were evident on 23%
(22/94) of computed tomography and 50% (67/134) of magnetic resonance imaging
studies in the acute setting. Twenty children with normal admission computed
tomography had abnormal findings on magnetic resonance imaging performed within 2
days. Length of stay was significantly longer among children with abnormal acute
magnetic resonance imaging (P < 0.001) and correlated with increased complexity
(Spearman rho = 0.4, P < 0.001) categorized as: no imaging abnormality, meningeal
enhancement and/or focal nonenhancing lesion, multifocal lesions, confluent
lesions, and lesions plus diffusion restriction, hemorrhage, or hydrocephalus.
There was no correlation between neuroimaging findings and an identifiable
pathogen (P = 0.8). CONCLUSION: Abnormal magnetic resonance imaging findings are
more common than abnormal computed tomography findings in pediatric encephalitis.
Increasing complexity of magnetic resonance imaging findings correlated with
disease severity as evidenced by longer length of stay, but were not specific for
an identifiable pathogen using a standardized diagnostic encephalitis panel.
PMID- 25846459
TI - miR-29a modulates tumor necrosis factor-alpha-induced osteogenic inhibition by
targeting Wnt antagonists.
AB - We previously found that miR-29a was significantly downregulated in Ankylosing
spondylitis (AS) patients, a chronic inflammatory disease associated with bone
metabolic disorder, however, the underlying mechanism remains unclear. In this
study, we demonstrated that miR-29a regulates tumor necrosis factor-alpha (TNF
alpha) mediated bone loss mainly by targeting DKK1 and GSK3beta, thus activating
the Wnt/beta-catenin pathway. Our findings may provide new insight into the
pathogenesis of the bone metabolism disorder in inflammation environment and
provide promising therapeutic target.
PMID- 25846460
TI - Protein adsorption, desorption, and aggregation mediated by solid-liquid
interfaces.
AB - Adsorption of proteins to solid-fluid interfaces is often empirically found to
promote formation of soluble aggregates and larger, subvisible, and visible
particles, but key stages in this process are often difficult to probe directly.
Aggregation mediated by adsorption to water-silicon oxide (SiOx) interfaces, akin
to hydrated glass surfaces, was characterized as a function of pH and ionic
strength for alpha-chymotrypsinogen (aCgn) and for a monoclonal antibody (IgG1).
A flow cell permitted neutron reflectivity for protein layers adsorbed to clean
SiOx surfaces, as well as after successive "rinse" steps. Aggregates recovered in
solution after gently "rinsing" the surface were characterized by neutron
scattering, microscopy, and fluorescence spectroscopy. IgG1 molecules oriented
primarily "flat" against the SiOx surface, with the primary protein layer
desorbed to a minimal extent, whereas a diffuse overlayer was easily rinsed off.
aCgn molecules were resistant to desorption when they appeared to be unfolded at
the interface, but were otherwise easily removed. For cases where strong binding
occurred, protein that did desorb was a mixture of monomer and small amounts of
HMW aggregates (for aCgn) or subvisible particles (for IgG1). Changes in
adsorption and/or unfolding with pH indicated that electrostatic interactions
were important in all cases.
PMID- 25846461
TI - [Wells Syndrome in children and atopy: Retrospective study of 11 cases and review
of the literature].
AB - BACKGROUND: Well's syndrome, or eosinophilic cellulitis, is rare in childhood,
with fewer than 40 pediatric cases being reported since 1979. The physiopathology
is unknown. PATIENTS AND METHODS: In February 2012, members of the research group
of the Department of Pediatric Dermatology Society submitted their case of Wells'
syndrome in children aged 0-15 years. Details of clinical, biological and
histological features and of therapeutic strategies were collected by physicians
using a standardized questionnaire. Pictures were reviewed by the authors.
RESULTS: Eleven patients were included (average age: 6 years), with a strong
prevalence of atopy (63%). Two types of clinical manifestation were noted: single
or multiple cellulitis associated or not with vesiculobullous lesions and fixed
urticaria. Eighty-two percent of patients had pruritus and 73% had eosinophilia.
For all patients, histological examination of skin biopsies showed an
eosinophilic infiltrate extending in the dermis with associated Sweet-like
neutrophilic infiltrate being seen in 2 patients. The course of the disease was
protracted (mean duration: 8 months) with flare-ups. Treatment varied depending
on the doctors (topical or systemic steroids, tacrolimus and dapsone).
DISCUSSION: Our study confirms some of the data in the literature concerning the
clinical, histological features and course of Well's syndrome in children. The
key information is the high prevalence of atopic children hitherto unreported. In
a setting of insect bites, vaccination, infection or traumatism, this unusual
background could explain the onset of inflammatory reaction with eosinophils.
Oral or topical steroids appear to be the first-line treatment in children when
necessary. CONCLUSION: Well's syndrome in children is rare and characterized by
its polymorphism. We report for the first time in a series of patients a high
prevalence of atopy, which raises new perspectives in understanding these rare
diseases. We propose topical steroids as first-line therapy in children with
superficial lesions, with oral steroids being given for cellulitic lesions or
where topical therapy fails.
PMID- 25846462
TI - [Item 197 - UE 7 Organ transplantation: skin complications].
PMID- 25846465
TI - [Foreword].
PMID- 25846463
TI - [Item 165 - UE 6 HIV infection: mucocutaneous manifestations of primary infection
with HIV].
PMID- 25846464
TI - [Item 183 - UE 7 Mucocutaneous hypersensitivity and allergies in children and
adults].
PMID- 25846466
TI - [Item 110 - UE 4 Autoimmune bullous dermatosis].
PMID- 25846467
TI - [Acute finger ischemia: A retrospective study of 13 patients].
AB - BACKGROUND: Acute ischemia of the upper limbs is rare in comparison with ischemia
of the lower limbs. The origins of this condition are varied. GOALS: We
retrospectively analyzed cases of acute finger ischemia (Raynaud's phenomena was
excluded) in a dermatology department between 2008 and 2013 in order to evaluate
the etiology and management of this phenomenon. RESULTS: Thirteen cases of finger
ischemia were reported. The mean age was 54 years. Active smoking was noted in 11
cases. Ischemia was acute in 9 cases and subacute in 4 cases. The location was
unilateral in 10 cases and bilateral in 2. Etiologies were: dysplasia of the
palmar arch, antiphospholipid antibody syndrome, frostbite, distal arteritis
linked to smoking, paraneoplastic arteritis, Buerger's disease, polyarteritis
nodosa, stenosis of the subclavian artery, and 3 cases of embolic origin (ulnar,
cardiac, and paraneoplastic aneurysm). In the acute phase, antiplatelets were
given in 6 cases, anticoagulants in 10 cases and ilomedin in 6 cases.
Sympathectomy was performed in 1 case and amputation in 2 cases. DISCUSSION: This
study illustrates the diversity of etiologies of finger ischemia. The etiological
test battery should be broad and include immunological and thrombophilia tests,
arterial and cardiac investigations, cervical radiography and CT scan (screening
for cancer). Close collaboration between dermatologists, hematologists, vascular
surgeons and radiologists is essential for the management of these patients.
PMID- 25846468
TI - [Item 113 - UE 4 Pruritus].
PMID- 25846469
TI - [Item 109 - UE 4 Facial dermatoses: acne, rosacea, seborrheic dermatitis].
PMID- 25846470
TI - [Item 152 - UE 6 Mucocutaneous mycotic and and bacterial infections].
PMID- 25846471
TI - [Item 112 - UE 4 Exanthema and erythroderma].
PMID- 25846472
TI - [Item 111 - UE 4 Hemangiomas and skin vascular malformations].
PMID- 25846473
TI - [Item 160 - UE 6 Febrile childhood exanthemas].
PMID- 25846475
TI - Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte
cytoplasm.
AB - Although tumor-associated fetal protein AFP has demonstrated utility as a
clinical tumor marker, the significance of intracellular AFP is still unclear.
The aim of this study was to explore the role of cytoplasmic AFP during HBx
induced carcinogenesis, which had not previously been recognized; 614 HCC
patients were analyzed for correlation of HBV infection with AFP level, and much
higher AFP levels were found in HBsAg positive patients. Tumor tissue specimens
from 20 HCC patients were used for analysis of AFP and GADD45alpha. Analysis of
HCC specimens showed that upregulation of cytoplasmic AFP is associated with down
regulation of GADD45alpha in neoplastic tissue. Transfected HBx promotes
transcription of AFP by acting on the elements in the AFP gene regulatory region.
HBx itself did not directly impact transcription of GADD45alpha. However, the
obstruction of RAR signaling by HBx induced elevation of AFP, which led to down
regulation of GADD45alpha. Cytoplasmic AFP was able to interact with RAR,
disrupting its entrance into the nucleus and binding to the elements in the
regulatory region of the GADD45alpha gene. Knockdown of AFP in siRNA-transfected
AFP positive cell lines was synchronously associated with an incremental increase
of RAR binding to DNA, as well as upregulation of GADD45alpha and it was contrary
in AFP gene-transfected AFP negative cell lines. These results indicate
cytoplasmic AFP is not only a histochemical tumor biomarker for human hepatoma
but is also an intracellular signal molecule and potential participant in HBx
induced hepatocarcinogenesis.
PMID- 25846474
TI - [Item 190 - UE 7 Disseminated lupus erythematosus. Antiphospholipid syndrome].
PMID- 25846476
TI - Should patients prescribed long-term low-dose aspirin receive proton pump
inhibitors? A systematic review and meta-analysis.
AB - BACKGROUND: Several clinical guidelines recommend the use of proton pump
inhibitors (PPIs) in patients taking low-dose aspirin but report no or limited
supporting data. We conducted a systematic review and meta-analysis to examine
the effects of co-administration of PPIs in patients taking low-dose aspirin on
the risks of adverse gastrointestinal (GI) and cardiovascular (CV) events, and on
patient adherence to aspirin. METHODS: We searched PUBMED, EMBASE and Cochrane
Central Register of Controlled Trials databases for relevant articles published
through November 2013. We included randomised controlled trials (RCTs) and
observational studies in patients taking low-dose aspirin with and without PPIs.
Risk of bias was assessed using the Cochrane Collaboration's tool (for RCTs) and
the Newcastle-Ottawa Scale (for observational studies). Pooled risk ratios (RRs)
were computed using a random-effects model. RESULTS: We included 13 studies, of
which 12 (2 RCTs and 10 observational studies) reported on GI events, and one
(cohort study) on both GI bleeding and CV events. No study reported on adherence
to aspirin. Co-administration of PPIs in patients receiving low-dose aspirin was
associated with risk reductions of 73% (RR 0.27, 95% CI 0.17-0.42) and 50% (RR
0.50, 95% CI 0.32-0.80) in the occurrence of peptic ulcer and GI bleeding
respectively. There was evidence of bias in publications reporting on the GI
events. CONCLUSIONS: The practice of co-prescribing PPIs in patients taking low
dose aspirin is supported by some data, but the evidence is rather weak. It
currently remains unclear whether the benefits of co-administration of PPIs in
users of low-dose aspirin outweigh their potential harms.
PMID- 25846477
TI - Selective Cyclization of Arylnitrones to Indolines under External Oxidant-Free
Conditions: Dual Role of Rh(III) Catalyst in the C-H Activation and Oxygen Atom
Transfer.
AB - The first example of Rh(III)-catalyzed cyclization of arylnitrones to indolines
under external oxidant-free conditions is presented. An intermolecular coupling
of arylnitrones with internal alkynes is made possible by the dual role of the
Cp*Rh(III) catalyst mediating both the C-H bond activation and O-atom transfer.
Synthetically important and pharmacologically privileged indoline derivatives
were obtained in good yields with high diastereoselectivity.
PMID- 25846478
TI - Plant community structure regulates responses of prairie soil respiration to
decadal experimental warming.
AB - Soil respiration is recognized to be influenced by temperature, moisture, and
ecosystem production. However, little is known about how plant community
structure regulates responses of soil respiration to climate change. Here, we
used a 13-year field warming experiment to explore the mechanisms underlying
plant community regulation on feedbacks of soil respiration to climate change in
a tallgrass prairie in Oklahoma, USA. Infrared heaters were used to elevate
temperature about 2 degrees C since November 1999. Annual clipping was used to
mimic hay harvest. Our results showed that experimental warming significantly
increased soil respiration approximately from 10% in the first 7 years (2000
2006) to 30% in the next 6 years (2007-2012). The two-stage warming stimulation
of soil respiration was closely related to warming-induced increases in ecosystem
production over the years. Moreover, we found that across the 13 years, warming
induced increases in soil respiration were positively affected by the proportion
of aboveground net primary production (ANPP) contributed by C3 forbs. Functional
composition of the plant community regulated warming-induced increases in soil
respiration through the quantity and quality of organic matter inputs to soil and
the amount of photosynthetic carbon (C) allocated belowground. Clipping, the
interaction of clipping with warming, and warming-induced changes in soil
temperature and moisture all had little effect on soil respiration over the years
(all P > 0.05). Our results suggest that climate warming may drive an increase in
soil respiration through altering composition of plant communities in grassland
ecosystems.
PMID- 25846479
TI - Unintended allergens in precautionary labelled and unlabelled products pose
significant risks to UK allergic consumers.
AB - BACKGROUND: Allergens in food may pose a risk to allergic consumers. While there
is EU regulation for allergens present as an ingredient, this is not the case for
unintended allergen presence (UAP). Food companies use precautionary allergen
labels to inform allergic individuals of a potential risk from UAPs. This study
investigates the risk of an allergic reaction within the milk-, wheat-, hazelnut-
and peanut-allergic populations when ingesting UK foods across multiple product
categories with and without precautionary allergen labelling. METHODS: Allergen
risk assessment using probabilistic techniques enables the estimation of the
residual risk after the consumption of a product that unintentionally contains an
allergen. RESULTS: Within this selection of UK products, the majority that tested
positive for an allergen contained a concentration of allergen predicted to cause
a reaction in >1% of the allergic population. The concentrations of allergens
measured were greater than the VITAL((r)) 2.0 action levels and would trigger
precautionary allergen labelling. This was found for products both with and
without precautionary allergen labelling. CONCLUSIONS: The results highlight the
need for the food industry and regulators to adopt a transparent, risk-based
approach for the communication of the risk associated with potential cross
contact that could occur in the processing facility or production chain.
PMID- 25846480
TI - Hill-Sachs lesion location: does it play a role in engagement?
AB - OBJECTIVE: To see if there is an association between engagement on physical
examination (PE) and the location of the Hill-Sachs lesion (HSL) as assessed by
the modified biceps angle. MATERIALS AND METHODS: Sixty-two patients with a
history of anterior shoulder dislocation, who underwent preoperative MRI and
arthroscopy at our institution and were tested for engagement on PE, were
collected. Two musculoskeletal radiologists reviewed the MR studies, noting the
presence of an HSL and documenting the location of the HSL with the modified
biceps angle. Statistical analysis included the Mann-Whitney (MW) test and ROC
(receiver-operating characteristic) curve. RESULTS: Of 62 patients, there were 58
males and 4 females with a mean age of 30 (range 18-59 years). Twenty patients
demonstrated engagement on PE, while 42 did not. All patients had evidence of an
HSL on MRI and arthroscopy. The mean biceps angle for the engaging group was
151.5 +/- 13.9 degrees , and 142.4 +/- 17.3 degrees for the non-engaging group.
The biceps angle was statistically significantly higher among patients who had
engagement compared to those who did not (p = 0.027). Overall, diagnostic
accuracy was highest for a biceps angle >149 degrees , which resulted in a
sensitivity of 70% and specificity of 67%. CONCLUSION: The modified biceps angle,
as measured on MRI, was significantly higher in patients who demonstrated
engagement on physical examination than in those who did not. This supports the
theory that the location of the Hill-Sachs lesion may play a role in engagement
and may be its most important characteristic when determining its significance.
PMID- 25846481
TI - Histone deacetylase 3 inhibition improves glycaemia and insulin secretion in
obese diabetic rats.
AB - Failure of pancreatic beta cells to compensate for insulin resistance is a
prerequisite for the development of type 2 diabetes. Sustained elevated
circulating levels of free fatty acids and glucose contribute to beta-cell
failure. Selective inhibition of histone deacetylase (HDAC)-3 protects pancreatic
beta cells against inflammatory and metabolic insults in vitro. In the present
study, we tested the ability of a selective HDAC3 inhibitor, BRD3308, to reduce
hyperglycaemia and increase insulin secretion in a rat model of type 2 diabetes.
At diabetes onset, an ambulatory hyperglycaemic clamp was performed. HDAC3
inhibition improved hyperglycaemia over the study period without affecting weight
gain. At the end of the hyperglycaemic clamp, circulating insulin levels were
significantly higher in BRD3308-treated rats. Pancreatic insulin staining and
contents were also significantly higher. These findings highlight HDAC3 as a key
therapeutic target for beta-cell protection in type 2 diabetes.
PMID- 25846482
TI - Acid mine drainage neutralization in a pilot sequencing batch reactor using
limestone from a paper and pulp industry.
AB - This study investigated the implications of using two grades of limestone from a
paper and pulp industry for neutralization of acid mine drainage (AMD) in a pilot
sequencing batch reactor (SBR). In this regard, two grades of calcium carbonate
were used to neutralize AMD in a SBR with a hydraulic retention time (including
settling) of 100 min and a sludge retention time of 360 min, by simultaneously
monitoring the Fe(II) removal kinetics and overall assessment of the AMD after
treatment. The Fe(II) kinetics removal and overall AMD treatment were observed to
be highly dependent on the limestone grade used, with Fe(II) completely removed
to levels lower than 50 mg/L in cycle 1 after 30 min using high quality or pure
paper and pulp limestone. On the contrary, the other grade limestone, namely
waste limestone, could only achieve a similar Fe(II) removal efficiency after
four cycles. It was also noticed that suspended solids concentration plays a
significant role in Fe(II) removal kinetics. In this regard, using pure limestone
from the paper and pulp industry will have advantages compared with waste
limestone for AMD neutralization. It has significant process impacts for the SBR
configuration as it allows one cycle treatment resulting in a significant
reduction of the feed stock, with subsequent generation of less sludge during AMD
neutralization. However, the use of waste calcium carbonate from the paper and
pulp industry as a feed stock during AMD neutralization can achieve significant
cost savings as it is cheaper than the pure limestone and can achieve the same
removal efficiency after four cycles.
PMID- 25846483
TI - Inverse association between serum total bilirubin levels and diabetic peripheral
neuropathy in patients with type 2 diabetes.
AB - Several studies have suggested that bilirubin, a potent innate antioxidant, plays
a protective role against cardiovascular and microvascular disease. This study
investigated the association between serum concentrations of total bilirubin (TB)
and the presence of diabetic peripheral neuropathy (DPN) in Korean diabetic
patients. This cross-sectional study involved 1207 patients aged more than 30
years with type 2 diabetes. DPN was assessed according to clinical symptoms and
physical examinations using Michigan Neuropathy Screening Instrument examination
score, 10-g monofilament sensation, and current perception threshold. The
subjects were stratified into gender-specific tertiles based on TB values, and
the relationship between the TB values and DPN was analyzed. Compared with
patients within the lowest TB tertile, those with higher TB levels consisted of
patients with shorter duration of diabetes, lower HbA1c, better renal function,
and less autonomic neuropathy, retinopathy, and albuminuria. Serum TB levels were
inversely associated with DPN. In multivariate analysis for the development of
DPN after adjusting for potential confounding factors including retinopathy,
albuminuria, and autonomic neuropathy, the TB levels were inversely associated
with the presence of DPN, both as a continuous variable [odds ratio (OR) per log
standard deviation (SD) 0.79; 95% confidence interval (CI) 0.65-0.97; P = 0.022]
and when categorized in tertiles (the highest vs. the lowest tertile; OR 0.63;
95% CI 0.40-0.99; P = 0.046). Low serum bilirubin levels are significantly
associated with DPN, independently of classic risk factors and other
microvascular complications. Further investigation is necessary to determine
whether serum bilirubin has a prognostic significance on DPN.
PMID- 25846485
TI - Practice may not always make perfect (outcomes).
PMID- 25846484
TI - Nanocurcumin protects cardiomyoblasts H9c2 from hypoxia-induced hypertrophy and
apoptosis by improving oxidative balance.
AB - Hypoxia-induced cardiomyocyte hypertrophy is evident; however, the distinct
molecular mechanism underlying the oxidative stress-mediated damages to
cardiomyocytes remains unknown. Curcumin (diferuloylmethane) is known for anti
hypertrophic effects, but low bioavailability makes it unsuitable to exploit its
pharmacological properties. We assessed the efficacy of nanotized curcumin, i.e.
nanocurcumin, in ameliorating hypoxia-induced hypertrophy and apoptosis in H9c2
cardiomyoblasts and compared it to curcumin. H9c2 cardiomyoblasts were challenged
with 0.5 % oxygen, for 24 h to assess hypoxia-induced oxidative damage,
hypertrophy and consequent apoptosis. The molecular mechanism underlying the
protective efficacy of nanocurcumin was evaluated in regulating Raf-1/Erk-1/2
apoptosis by caspase-3/-7 pathway and oxidative stress. Nanocurcumin ameliorated
hypoxia-induced hypertrophy and apoptosis in H9c2 cells significantly (p <=
0.01), by downregulating atrial natriuretic factor expression, caspase-3/-7
activation, oxidative stress and stabilizing hypoxia-inducible factor-1alpha (HIF
1alpha) better than curcumin. Nanocurcumin provides insight into its use as a
potential candidate in curing hypoxia-induced cardiac pathologies by restoring
oxidative balance.
PMID- 25846487
TI - The tail of the epidemic and the challenge of tracing the very last Ebola case.
PMID- 25846488
TI - Ebola response missions: to go or not to go? Cross-sectional study on the
motivation of European public health experts, December 2014.
AB - We surveyed European infectious disease epidemiologists and microbiologists about
their decisions to apply for Ebola response missions. Of 368 respondents, 49
(15%) had applied. Applicants did not differ from non-applicants in terms of age,
sex or profession but had more training in field epidemiology and more
international experience. Common concerns included lack of support from families
and employers. Clearer terms of reference and support from employers could
motivate application and support outbreak response in West Africa.
PMID- 25846486
TI - Nerve growth factor promotes reorganization of the axonal microtubule array at
sites of axon collateral branching.
AB - The localized debundling of the axonal microtubule array and the entry of
microtubules into axonal filopodia are two defining features of collateral
branching. We report that nerve growth factor (NGF), a branch-inducing signal,
increases the frequency of microtubule debundling along the axon shaft of chicken
embryonic sensory neurons. Sites of debundling correlate strongly with the
localized targeting of microtubules into filopodia. Platinum replica electron
microscopy suggests physical interactions between debundled microtubules and
axonal actin filaments. However, as evidenced by depolymerization of actin
filaments and inhibition of myosin II, actomyosin force generation does not
promote debundling. In contrast, loss of actin filaments or inhibition of myosin
II activity promotes debundling, indicating that axonal actomyosin forces
suppress debundling. MAP1B is a microtubule associated protein that represses
axon branching. Following treatment with NGF, microtubules penetrating filopodia
during the early stages of branching exhibited lower levels of associated MAP1B.
NGF increased and decreased the levels of MAP1B phosphorylated at a GSK-3beta
site (pMAP1B) along the axon shaft and within axonal filopodia, respectively. The
levels of MAP1B and pMAP1B were not altered at sites of debundling, relative to
the rest of the axon. Unlike the previously determined effects of NGF on the
axonal actin cytoskeleton, the effects of NGF on microtubule debundling were not
affected by inhibition of protein synthesis. Collectively, these data indicate
that NGF promotes localized axonal microtubule debundling, that actomyosin forces
antagonize microtubule debundling, and that NGF regulates pMAP1B in axonal
filopodia during the early stages of collateral branch formation.
PMID- 25846489
TI - Australian Hajj pilgrims' knowledge, attitude and perception about Ebola,
November 2014 to February 2015.
AB - Upon return from Hajj 2014, 150 Australian pilgrims were interviewed about their
understanding of the Ebola epidemic. Most (89%, 134/150) knew of the epidemic
before travelling and 60% (80/134) of those knew Ebola transmits through body
fluids. Pilgrims who received pre-travel health advice were more conscious of
Ebola (69% vs 31%, p = 0.01) and adhered better to hand hygiene after touching an
ill person (68% vs 31%, p < 0.01). Mass media was the main information source
(78%).
PMID- 25846490
TI - Evaluation of a point-of-care blood test for identification of Ebola virus
disease at Ebola holding units, Western Area, Sierra Leone, January to February
2015.
AB - Current Ebola virus disease (EVD) diagnosis relies on reverse transcription-PCR
(RT-PCR) technology, requiring skilled laboratory personnel and technical
infrastructure. Lack of laboratory diagnostic capacity has led to diagnostic
delays in the current West African EVD outbreak of 2014 and 2015, compromising
outbreak control. We evaluated the diagnostic accuracy of the EVD bedside rapid
diagnostic antigen test (RDT) developed by the United Kingdom's Defence Science
and Technology Laboratory, compared with Ebola virus RT-PCR, in an operational
setting for EVD diagnosis of suspected cases admitted to Ebola holding units in
the Western Area of Sierra Leone. From 22 January to 16 February 2015, 138
participants were enrolled. EVD prevalence was 11.5%. All EVD cases were
identified by a positive RDT with a test line score of 6 or more, giving a
sensitivity of 100% (95% confidence interval (CI): 78.2-100). The corresponding
specificity was high (96.6%, 95% CI: 91.3-99.1). The positive and negative
predictive values for the population prevalence were 79.0% (95% CI: 54.4-93.8)
and 100% (95% CI: 96.7-100), respectively. These results, if confirmed in a
larger study, suggest that this RDT could be used as a 'rule-out' screening test
for EVD to improve rapid case identification and resource allocation.
PMID- 25846491
TI - Wild bird surveillance around outbreaks of highly pathogenic avian influenza
A(H5N8) virus in the Netherlands, 2014, within the context of global flyways.
AB - Highly pathogenic avian influenza (HPAI) A(H5N8) viruses that emerged in poultry
in east Asia since 2010 spread to Europe and North America by late 2014. Despite
detections in migrating birds, the role of free-living wild birds in the global
dispersal of H5N8 virus is unclear. Here, wild bird sampling activities in
response to the H5N8 virus outbreaks in poultry in the Netherlands are summarised
along with a review on ring recoveries. HPAI H5N8 virus was detected exclusively
in two samples from ducks of the Eurasian wigeon species, among 4,018 birds
sampled within a three months period from mid-November 2014. The H5N8 viruses
isolated from wild birds in the Netherlands were genetically closely related to
and had the same gene constellation as H5N8 viruses detected elsewhere in Europe,
in Asia and in North America, suggesting a common origin. Ring recoveries of
migratory duck species from which H5N8 viruses have been isolated overall provide
evidence for indirect migratory connections between East Asia and Western Europe
and between East Asia and North America. This study is useful for better
understanding the role of wild birds in the global epidemiology of H5N8 viruses.
The need for sampling large numbers of wild birds for the detection of H5N8 virus
and H5N8-virus-specific antibodies in a variety of species globally is
highlighted, with specific emphasis in north-eastern Europe, Russia and northern
China.
PMID- 25846492
TI - Laboratory support during and after the Ebola virus endgame: towards a sustained
laboratory infrastructure.
AB - The Ebola virus epidemic in West Africa is on the brink of entering a second
phase in which the (inter)national efforts to slow down virus transmission will
be engaged to end the epidemic. The response community must consider the
longevity of their current laboratory support, as it is essential that diagnostic
capacity in the affected countries be supported beyond the end of the epidemic.
The emergency laboratory response should be used to support building structural
diagnostic and outbreak surveillance capacity.
PMID- 25846493
TI - Surveillance and Outbreak Response Management System (SORMAS) to support the
control of the Ebola virus disease outbreak in West Africa.
AB - In the context of controlling the current outbreak of Ebola virus disease (EVD),
the World Health Organization claimed that 'critical determinant of epidemic size
appears to be the speed of implementation of rigorous control measures', i.e.
immediate follow-up of contact persons during 21 days after exposure, isolation
and treatment of cases, decontamination, and safe burials. We developed the
Surveillance and Outbreak Response Management System (SORMAS) to improve
efficiency and timeliness of these measures. We used the Design Thinking
methodology to systematically analyse experiences from field workers and the
Ebola Emergency Operations Centre (EOC) after successful control of the EVD
outbreak in Nigeria. We developed a process model with seven personas
representing the procedures of EVD outbreak control. The SORMAS system
architecture combines latest In-Memory Database (IMDB) technology via SAP HANA
(in-memory, relational database management system), enabling interactive data
analyses, and established SAP cloud tools, such as SAP Afaria (a mobile device
management software). The user interface consists of specific front-ends for
smartphones and tablet devices, which are independent from physical
configurations. SORMAS allows real-time, bidirectional information exchange
between field workers and the EOC, ensures supervision of contact follow-up,
automated status reports, and GPS tracking. SORMAS may become a platform for
outbreak management and improved routine surveillance of any infectious disease.
Furthermore, the SORMAS process model may serve as framework for EVD outbreak
modeling.
PMID- 25846494
TI - Identification of common features of vehicle motion under drowsy/distracted
driving: A case study in Wuhan, China.
AB - Drowsy/distracted driving has become one of the leading causes of traffic crash.
Only certain particular drowsy/distracted driving behaviors have been studied by
previous studies, which are mainly based on dedicated sensor devices such as bio
and visual sensors. The objective of this study is to extract the common features
for identifying drowsy/distracted driving through a set of common vehicle motion
parameters. An intelligent vehicle was used to collect vehicle motion parameters.
Fifty licensed drivers (37 males and 13 females, M=32.5 years, SD=6.2) were
recruited to carry out road experiments in Wuhan, China and collecting vehicle
motion data under four driving scenarios including talking, watching roadside,
drinking and under the influence of drowsiness. For the first scenario, the
drivers were exposed to a set of questions and asked to repeat a few sentences
that had been proved valid in inducing driving distraction. Watching roadside,
drinking and driving under drowsiness were assessed by an observer and self
reporting from the drivers. The common features of vehicle motions under four
types of drowsy/distracted driving were analyzed using descriptive statistics and
then Wilcoxon rank sum test. The results indicated that there was a significant
difference of lateral acceleration rates and yaw rate acceleration between
"normal driving" and drowsy/distracted driving. Study results also shown that,
under drowsy/distracted driving, the lateral acceleration rates and yaw rate
acceleration were significantly larger from the normal driving. The lateral
acceleration rates were shown to suddenly increase or decrease by more than
2.0m/s(3) and the yaw rate acceleration by more than 2.5 degrees /s(2). The
standard deviation of acceleration rate (SDA) and standard deviation of yaw rate
acceleration (SDY) were identified to as the common features of vehicle motion
for distinguishing the drowsy/distracted driving from the normal driving. In
order to identify a time window for effectively extracting the two common
features, a double-window method was used and the optimized "Parent Window" and
"Child Window" were found to be 55s and 6s, respectively. The study results can
be used to develop a driving assistant system, which can warn drivers when any
one of the four types of drowsy/distracted driving is detected.
PMID- 25846495
TI - Quantum confinement-tunable intersystem crossing and the triplet state lifetime
of cationic porphyrin-CdTe quantum dot nano-assemblies.
AB - Here, we report a ground-state interaction between the positively charged
cationic porphyrin and the negatively charged carboxylate groups of the thiol
ligands on the surface of CdTe quantum dots (QDs), leading to the formation of a
stable nanoassembly between the two components. Our time-resolved data clearly
demonstrate that we can dramatically tune the intersystem crossing (ISC) and the
triplet state lifetime of porphyrin by changing the size of the QDs in the
nanoassembly.
PMID- 25846496
TI - Clinical and pathological correlations of marrow PUMA and P53 expressions in
myelodysplastic syndromes.
AB - p53 is a key regulator of apoptosis. p53 upregulated modulator of apoptosis
(PUMA) is a critical mediator of p53-dependent and independent apoptosis. The
objective of this study was to evaluate the relationship of p53 and PUMA to the
prognosis of MDS. Bone marrow biopsies of MDS patients at the time of diagnosis
(n = 76) and at the time of transformation (n = 19) were included in the study
group. The expression of p53 and PUMA was evaluated using immunohistochemistry.
When compared to the control group, both p53 (p < 0.001) and PUMA (p = 0.012)
expression levels were significantly higher in MDS group. In MDS group, there was
a moderate positive correlation between p53 and PUMA expressions. PUMA expression
was not correlated with event free and overall survival. However, overall
survival was significantly lower in cases with p53 expression in more than 50% of
the cells. There was an increase in PUMA expression in cases that showed
transformation as compared to the initial diagnostic bone marrows but was not
statistically significant. The correlation that existed between p53 and PUMA was
lost in transformed cases. Our results showed that PUMA and p53 expressions are
increased in MDS marrows compared to normal marrows. PUMA expression increases
further during transformation while the expression of p53 is not significantly
altered which suggests that PUMA alterations might be a late event during the
evolution of MDS.
PMID- 25846497
TI - Noncanonical Wnt5a-Ca(2+) -NFAT signaling axis in pesticide induced bone marrow
aplasia mouse model: A study to explore the novel mechanism of pesticide
toxicity.
AB - According to case-control studies, long-term pesticide exposure can cause bone
marrow aplasia like hematopoietic degenerative disease leading to impaired
hematopoiesis and increased risk of aplastic anemia in human subjects. However,
the exact mechanism of pesticide mediated hematotoxicity still remains elusive.
In this study, we investigated the role of noncanonical Wnt signaling pathway, a
crucial regulator of adult hematopoiesis, in pesticide induced bone marrow
aplasia mouse model. Aplasia mouse model was developed following inhalation and
dermal exposure of 5% aqueous mixture of common agriculturally used pesticides
for 6 h/day for 5 days a week up to 90 days. After that, blood hemogram, marrow
smear, cellularity, scanning electron microscopy, extramedullary hematopoiesis
and flowcytometric expression analysis of noncanonical Wnt signaling components,
such as Wnt 5a, fzd5, NFAT, IFN-gamma, intracellular Ca(2+) level were evaluated
in the bone marrow hematopoietic stem/progenitor compartment of the control and
pesticide induced aplasia groups of animals. Results showed that pesticide
exposed mice were anemic with peripheral blood pancytopenia, hypocellular
degenerative marrow, and extramedullary hematopoiesis in the spleen. Upon
pesticide exposure, Wnt 5a expression was severely downregulated with a decline
in intracellular Ca(2+) level. Moreover, downstream of Wnt5a, we observed sharp
downregulation of NFATc2 transcription factor expression, the major target of
pesticide toxicity and its target molecule IFN-gamma. Taken together, our result
suggests that deregulation of Wnt5a-Ca(2+) -NFAT signaling axis in the
hematopoietic stem/progenitor compartment plays a crucial role behind the
pathogenesis of pesticide mediated bone marrow aplasia by limiting primitive
hematopoietic stem cells' ability to maintain hematopoietic homeostasis and
reconstitution mechanism in vivo during xenobiotic stress leading to ineffective
hematopoiesis and evolution of bone marrow aplasia. (c) 2015 Wiley Periodicals,
Inc. Environ Toxicol 31: 1163-1175, 2016.
PMID- 25846498
TI - Role of hepatocyte S6K1 in palmitic acid-induced endoplasmic reticulum stress,
lipotoxicity, insulin resistance and in oleic acid-induced protection.
AB - The excess of saturated free fatty acids, such as palmitic acid, that induces
lipotoxicity in hepatocytes, has been implicated in the development of non
alcoholic fatty liver disease also associated with insulin resistance. By
contrast, oleic acid, a monounsaturated fatty acid, attenuates the effects of
palmitic acid. We evaluated whether palmitic acid is directly associated with
both insulin resistance and lipoapoptosis in mouse and human hepatocytes and the
impact of oleic acid in the molecular mechanisms that mediate both processes. In
human and mouse hepatocytes palmitic acid at a lipotoxic concentration triggered
early activation of endoplasmic reticulum (ER) stress-related kinases, induced
the apoptotic transcription factor CHOP, activated caspase 3 and increased the
percentage of apoptotic cells. These effects concurred with decreased IR/IRS1/Akt
insulin pathway. Oleic acid suppressed the toxic effects of palmitic acid on ER
stress activation, lipoapoptosis and insulin resistance. Besides, oleic acid
suppressed palmitic acid-induced activation of S6K1. This protection was mimicked
by pharmacological or genetic inhibition of S6K1 in hepatocytes. In conclusion,
this is the first study highlighting the activation of S6K1 by palmitic acid as a
common and novel mechanism by which its inhibition by oleic acid prevents ER
stress, lipoapoptosis and insulin resistance in hepatocytes.
PMID- 25846499
TI - In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound
healing effects and cytotoxicity/genotoxicity profile.
AB - Oxidative stress occurs following the impairment of pro-oxidant/antioxidant
balance in chronic wounds and leads to harmful delays in healing progress. A fine
balance between oxidative stress and endogenous antioxidant defense system may be
beneficial for wound healing under redox control. This study tested the
hypothesis that oxidative stress in wound area can be controlled with systemic
antioxidant therapy and therefore wound healing can be accelerated. We used
chlorogenic acid (CGA), a dietary antioxidant, in experimental diabetic wounds
that are characterized by delayed healing. Additionally, we aimed to understand
possible side effects of CGA on pivotal organs and bone marrow during therapy.
Wounds were created on backs of streptozotocin-induced diabetic rats. CGA (50
mg/kg/day) was injected intraperitoneally. Animals were sacrificed on different
days. Biochemical and histopathological examinations were performed. Side effects
of chronic antioxidant treatment were tested. CGA accelerated wound healing,
enhanced hydroxyproline content, decreased malondialdehyde/nitric oxide levels,
elevated reduced-glutathione, and did not affect superoxide dismutase/catalase
levels in wound bed. While CGA induced side effects such as cyto/genotoxicity, 15
days of treatment attenuated blood glucose levels. CGA decreased lipid
peroxidation levels of main organs. This study provides a better understanding
for antioxidant intake on diabetic wound repair and possible pro-oxidative
effects.
PMID- 25846500
TI - Cytotoxicity, cell uptake and microscopic analysis of titanium dioxide and silver
nanoparticles in vitro.
AB - Commercially manufactured nanomaterials are used massively for modification of
products of everyday use, including products intended for children. Therefore
their potential risks have to be ultimately studied. Aside from toxicity of
nanomaterials with known specific parameters, the end-consumer is potentially
endangered by materials with unknown specification. Commercially available
products are not usually accompanied by parameter/specification sheet providing
the consumer with sufficient chemico-physical parameters allowing the evaluation
of possible toxic effects. The aim of this work was to evaluate the declared
parameters of commercially available TiO2 and Ag NPs employing chemico-physical
methods and consequently in vitro cytotoxicity and genotoxicity tests performed
on non-cancer cell lines. Based on the results of our complex study we can
conclude that the data provided by the producers are not in good agreement with
the performed measurements. Furthermore, all tested NPs penetrated into the SVK14
cells and all NPs had significant effect on the kinetics of ROS production in all
cell lines (note: the ROS production has not been established as the major
mechanism of cell damage elicited by Ag NPs). The study revealed greater
cytotoxic potential of Ag NPs in comparison with TiO2 NPs and all of the studied
NPs caused significant DNA damage.
PMID- 25846501
TI - Human systemic exposure to [14C]-paraphenylenediamine-containing oxidative hair
dyes: Absorption, kinetics, metabolism, excretion and safety assessment.
AB - Systemic exposure was measured in humans after hair dyeing with oxidative hair
dyes containing 2.0% (A) or 1.0% (B) [(14)C]-p-phenylenediamine (PPD). Hair was
dyed, rinsed, dried, clipped and shaved; blood and urine samples were collected
for 48 hours after application. [(14)C] was measured in all materials, rinsing
water, hair, plasma, urine and skin strips. Plasma and urine were also analysed
by HLPC/MS/MS for PPD and its metabolites (B). Total mean recovery of
radioactivity was 94.30% (A) or 96.21% (B). Mean plasma Cmax values were 132.6 or
97.4 ng [(14)C]-PPDeq/mL, mean AUC(0-infinity) values 1415 or 966 ng [(14)C]
PPDeq/mL*hr in studies A or B, respectively. Urinary excretion of [(14)C] mainly
occurred within 24 hrs after hair colouring with a total excretion of 0.72 or
0.88% of applied radioactivity in studies A or B, respectively. Only N,N'
diacetylated-PPD was detected in plasma and the urine. A TK-based human safety
assessment estimated margins of safety of 23.3- or 65-fold relative to respective
plasma AUC or Cmax values in rats at the NOAEL of a toxicity study. Overall, hair
dyes containing PPD are unlikely to pose a health risk since they are used
intermittently and systemic exposure is limited to the detoxified metabolite N,N'
diacetyl-PPD.
PMID- 25846502
TI - Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by
modulating inflammation, Erk and p38 in mice.
AB - Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6
noneamide) can act as a carcinogen or cocarcinogen. However, the influence of
consumption of capsaicin-containing foods or vegetables on skin cancer patients
remains largely unknown. In the present study, we demonstrated that capsaicin has
a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O
tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results
showed that topical application of capsaicin on the dorsal skin of DMBA-initiated
and TPA-promoted mice could significantly accelerate tumor formation and growth
and induce more and larger skin tumors than the model group (DMBA + TPA).
Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor
proliferation. Mechanistic study found that inflammation-related factors
cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly
elevated by pretreatment with capsaicin, suggesting an inflammation-dependent
mechanism. Furthermore, mice that were administered capsaicin exhibited
significant up-regulation of phosphorylation of nuclear factor kappaB (NF
kappaB), Erk and p38 but had no effect on JNK. Thus, our results indicated that
inflammation, Erk and P38 collectively played a crucial role in cancer-promoting
effect of capsaicin on carcinogen-induced skin cancer in mice.
PMID- 25846503
TI - Modulating effect of synthetic statins against damage induced by doxorubicin in
somatic cells of Drosophila melanogaster.
AB - The competitive inhibitors of HMG-CoA reductase, popularly known as statins,
exert pleiotropic effects, which result from the ability of statins to inhibit
the synthesis of isoprenoids, which are fundamental for the functioning of
proteins responsible for intracellular signaling. Some recent studies suggest an
important role associated with the use of antineoplastic atorvastatin and
rosuvastatin, the statins most widely used today. In this study, the Drosophila
wing spot test was used to evaluate possible protective effects of atorvastatin
and rosuvastatin against damage induced by DXR. Larvae were chronically treated
with negative control (ethanol 5%), positive control (DXR 0.125 mg/mL) and five
different concentrations of atorvastatin and rosuvastatin. The results
demonstrated absence of a mutagenic effect for the two statins tested. The
analysis of the descendants co-treated with DXR and atorvastatin/rosuvastatin
revealed a modulatory effect of these statins on damage induced by DXR. This
effect was verified in all concentrations tested in the descendants of the ST and
HB crosses treated with rosuvastatin, and only in descendants of the HB cross
treated with atorvastatin. Induction of apoptosis and antioxidant activity appear
to be the main mechanisms involved in reducing the frequency of mutant spots and
consequent modulation of the damage induced by DXR.
PMID- 25846504
TI - The Structural Stability of Graphene Anticorrosion Coating Materials is
Compromised at Low Potentials.
AB - Corrosion of engineered structures is a major problem causing an estimated
economic loss of more than 2 trillion US dollars annually worldwide. Graphene has
recently emerged as highly promising, low-cost, and transparent anticorrosion
coating material. Herein, it is shown that a multilayer graphene film grown on Ni
by chemical vapor deposition undergoes abrupt stability failure under galvanic
corrosion conditions. The multilayer graphene coating was examined by optical
microscopy, SEM, energy dispersive X-ray spectroscopy, Raman spectroscopy, and
cyclic voltammetry after exposure to potentials between 600 and 1300 mV in
alkaline solution. A fast and simple electrochemical method is proposed to
sensitively quantify the damage caused by the applied potential bias. It is based
on quantification of the oxidation signals generated by the underlying Ni-metal
catalyst that is exposed by damage to the graphene film. It is shown that film
damage can start at potentials as low as 900 mV and that macroscopic and
extensive damage can be caused at potentials above 1000 mV. In addition, once the
graphene film has been damaged, the corrosion rate of the underlying metal is
significantly increased. These findings are of great importance for potential
applications of multilayer graphene films in coating metal structures with huge
industrial and economic implications.
PMID- 25846505
TI - A library of synthetic transcription activator-like effector-activated promoters
for coordinated orthogonal gene expression in plants.
AB - A library of synthetic promoters containing the binding site of a single designer
transcription activator-like effector (dTALE) was constructed. The promoters
contain a constant sequence, consisting of an 18-base long dTALE-binding site and
a TATA box, flanked by degenerate sequences of 49 bases downstream and 19 bases
upstream. Forty-three of these promoters were sequenced and tested in transient
assays in Nicotiana benthamiana using a GUS reporter gene. The strength of
expression of the promoters ranged from around 5% to almost 100% of the viral 35S
promoter activity. We then demonstrated the utility of these promoters for
metabolic engineering by transiently expressing three genes for the production of
a plant diterpenoid in N. benthamiana. The simplicity of the promoter structure
shows great promise for the development of genetic circuits, with wide potential
applications in plant synthetic biology and metabolic engineering.
PMID- 25846511
TI - Quantification of turbulence and velocity in stenotic flow using spiral three
dimensional phase-contrast MRI.
AB - PURPOSE: Evaluate spiral three-dimensional (3D) phase contrast MRI for the
assessment of turbulence and velocity in stenotic flow. METHODS: A-stack-of
spirals 3D phase contrast MRI sequence was evaluated in vitro against a
conventional Cartesian sequence. Measurements were made in a flow phantom with a
75% stenosis. Both spiral and Cartesian imaging were performed using different
scan orientations and flow rates. Volume flow rate, maximum velocity and
turbulent kinetic energy (TKE) were computed for both methods. Moreover, the
estimated TKE was compared with computational fluid dynamics (CFD) data. RESULTS:
There was good agreement between the turbulent kinetic energy from the spiral,
Cartesian and CFD data. Flow rate and maximum velocity from the spiral data
agreed well with Cartesian data. As expected, the short echo time of the spiral
sequence resulted in less prominent displacement artifacts compared with the
Cartesian sequence. However, both spiral and Cartesian flow rate estimates were
sensitive to displacement when the flow was oblique to the encoding directions.
CONCLUSION: Spiral 3D phase contrast MRI appears favorable for the assessment of
stenotic flow. The spiral sequence was more than three times faster and less
sensitive to displacement artifacts when compared with a conventional Cartesian
sequence.
PMID- 25846513
TI - Recommendations for reporting histopathology studies: a proposal.
PMID- 25846514
TI - van Leeuwenhoek microscopes-where are they now?
AB - When Antonie van Leeuwenhoek died, he left over 500 simple microscopes,
aalkijkers (an adaption of his microscope to allow the examination of blood
circulation in the tails of small eels) and lenses, yet now there are only 10
microscopes with a claim to being authentic, one possible aalkijker and six
lenses. He made microscopes with more than one lens, and possibly three forms of
the aalkijker. This paper attempts to establish exactly what he left and trace
the fate of some of the others using the earliest possible documents and
publications.
PMID- 25846512
TI - Activation of platelet protease-activated receptor-1 induces epithelial
mesenchymal transition and chemotaxis of colon cancer cell line SW620.
AB - The aim of the present study was to examine the role of protease-activated
receptor-1 (PAR1)-stimulated platelet activation in the epithelial-mesenchymal
transition (EMT) and migration of colon cancer cells, and to identify the
underlying mechanisms. TFLLR-NH2, a PAR1 agonist, was used to activate platelets
and the platelet supernatants were used to treat the SW620 colon cancer cell
line. Expression of E-cadherin and vimentin on SW620 cells was detected by
immunofluorescence and western blotting, and the level of the transforming growth
factor beta1 (TGF-beta1) was measured using ELISA following the activation of
platelets by TFLLR-NH2. miR-200b expression was detected using quantitative PCR
in SW620 cells. In order to investigate the chemotactic ability of the SW620
cells, the expression of CXC chemokine receptor type 4 (CXCR4) was measured by
flow cytometry. Transwell migration assays were performed following exposure of
the cells to the supernatant of PAR1-activated platelets. SW620 cells cultured in
the supernatant of TFLLR-NH2-activated platelets upregulated E-cadherin
expression and downregulated the vimentin expression. In the in vitro platelet
culture system, a TFLLR-NH2 dose-dependent increase of secreted TGF-beta1 was
detected in the supernatant. The activation of PAR1 on the platelets led to the
inhibition of miR-200b expression in the SW620 cells that were cultured in
platelet-conditioned media. The number of SW620 cells that penetrated through the
Transwell membrane increased with the dose of TFLLR-NH2 used to treat the
platelets. The percentage of CXCR4-positive SW620 cells was significantly higher
when they were exposed to the supernatant of platelets cultured for 24 h with
PAR1 agonist than when cultured in non-conditioned media (40.89 +/- 6.74 vs. 3.47
+/- 1.40%, P < 0.01). Platelet activation with a PAR1 agonist triggered TGF-beta
secretion, which induced EMT of SW620 human colon cancer cells via the
downregulation of miR-200b expression, and activated platelets had a chemotactic
effect on colon cancer cells mediated by the upregulation of CXCR4 on the cell
surface.
PMID- 25846515
TI - Insight into proteomic investigations of Neisseria meningitidis serogroup C
strain L91543 from analysis of its genome sequence.
AB - Here, we describe the draft sequence of a virulent isolate of Neisseria
meningitidis strain L91543, belonging to serogroup C. The findings from previous
proteomic and metabolomic studies of this strain can now be further interpreted
with genomic analysis. Comparative analysis of the genome sequence revealed close
similarity and localized synteny with the genome sequence of N. meningitidis
serogroup C strain, FAM18. Polymorphisms were identified in the signal peptide
sequence of factor H binding protein, a target for new meningococcal vaccines,
which may result in its inefficient translocation across the cytoplasmic membrane
affecting its processing (lipidation and cleavage of the signal peptide) and
transportation to the outer membrane in strain L91543. This would explain the
unusual proteomic data for factor H binding protein for this strain. NadA,
another target for new vaccines, and the MtrR regulator, which controls
expression of NadA, both contain SNPs between strains L91543 and FAM18. The
genome sequence data were generated using Ion Torrent PGM sequencing, assembled
into 50 contigs with 64* coverage and annotated with 2262 genes, 14 rRNAs and 56
tRNAs. The availability of the genome of N. meningitidis strain L91543 will aid
our understanding of the proteome of this organism, importantly its vaccine
antigens.
PMID- 25846516
TI - Historical microbiology, is it relevant in the 21st century?
AB - Facsimile microscopes have been used to examine the possibilities of van
Leeuwenhoek microscopes with a range of magnifications, particularly to confirm
that bacteria can be seen if the microscope is strong enough. The relevance of
historical microbiology in education is also illustrated by adapting versions of
van Leeuwenhoek's pepper water experiment and Beijerinck's use of bioluminescent
bacteria as oxygen probes. These experiments can demonstrate fundamentals such as
enrichment and isolation cultures, physiology and experimental planning as well
as critical reading of published material.
PMID- 25846517
TI - Purging using the Heimlich maneuver among children and adolescents with eating
disorders.
AB - This case report describes five independent cases of children and adolescents
assessed for eating disorders who disclosed using the Heimlich maneuver as a
purging technique. The maneuver is meant to be used only in life or death
situations, likely once or less in any person's lifetime. A child or adolescent
with an eating disorder may be using it to self-induce vomiting on a daily basis,
increasing the risk of complications, including potential damage to major organs
of the body. Asking patients who purge to elaborate on the methods with which
they purge can provide clinicians with fuller information, improving their
ability to select appropriate medical tests and interventions. Thorough
investigations of physical complaints during the patient assessment may be
warranted, including examining patients for possible rib fractures, hemorrhages,
perforations of the hollow viscous, and other forms of blunt abdominal traumas.
PMID- 25846518
TI - Physical Stimuli-Induced Chondrogenic Differentiation of Mesenchymal Stem Cells
Using Magnetic Nanoparticles.
AB - Chondrogenic commitments of mesenchymal stem cells (MSCs) require 3D cellular
organization. Furthermore, recent progresses in bioreactor technology have
contributed to the development of various biophysical stimulation platforms for
efficient cartilage tissue formation. Here, an approach is reported to drive 3D
cellular organization and enhance chondrogenic commitment of bone-marrow-derived
human mesenchymal stem cells (BM-hMSCs) via magnetic nanoparticle (MNP)-mediated
physical stimuli. MNPs isolated from Magnetospirillum sp. AMB-1 are endocytosed
by the BM-hMSCs in a highly efficient manner. MNPs-incorporated BM-hMSCs are
pelleted and then subjected to static magnetic field and/or magnet-derived shear
stress. Magnetic-based stimuli enhance level of sulfated glycosaminoglycan (sGAG)
and collagen synthesis, and facilitate the chondrogenic differentiation of BM
hMSCs. In addition, both static magnetic field and magnet-derived shear stress
applied for the chondrogenic differentiation of BM-hMSCs do not show increament
of hypertrophic differentiation. This MNP-mediated physical stimulation platform
demonstrates a promising strategy for efficient cartilage tissue engineering.
PMID- 25846520
TI - Right and left inverted lobar lung transplantation.
AB - Adult recipients frequently withdraw from living-donor lobar lung transplantation
because of the small size of donor grafts. The right lower lobe is 120% larger
than the left lower lobe. We developed a novel surgical technique in which an
inverted right lower lobe graft can be transplanted into the left thorax. The
first patient was a 43-year-old woman with end-stage idiopathic interstitial
pneumonia. Her husband was the only eligible donor for living-donor lobar lung
transplantation. His right lower lobe was estimated to provide 45% of the
recipient's predicted forced vital capacity, which would provide the borderline
function required for living-donor lobar lung transplantation. Since lung
perfusion scintigraphy of the recipient showed a right-to-left ratio of 64:36,
transplanting the right lower lobe graft into the left thorax and sparing the
native right lung was considered the only treatment option. We simulated this
procedure using three-dimensional models produced by a three-dimensional printer.
In living-donor lobar lung transplantation, all anastomoses were performed
smoothly as planned preoperatively. Because of the initial success, this
procedure was performed successfully in two additional patients. This procedure
enables larger grafts to be transplanted, potentially solving critical size
matching problems in living-donor lobar lung transplantation.
PMID- 25846519
TI - Survival in relation to hospital type after resection or sorafenib treatment for
hepatocellular carcinoma in The Netherlands.
AB - BACKGROUND AND OBJECTIVE: Despite an increase in recent years, hepatocellular
carcinoma remains uncommon in the Netherlands. The aim of the current study is to
explore potential effects of hospital type and volume on outcomes after resection
or sorafenib in patients with hepatocellular carcinoma. METHODS: Initial
treatment and survival of patients with hepatocellular carcinoma diagnosed in the
period 2005-2011 were based on data of the Netherlands Cancer Registration.
Potential risk factors (including hospital type and volume) for 30-days
postoperative and long-term mortality in patients who underwent resection and in
patients treated with sorafenib were evaluated by uni- and multivariate analyses.
RESULTS: In the period 2005-2011, 2402 patients were diagnosed with
hepatocellular carcinoma: 12% received resection and 9% sorafenib. Postoperative
mortality was higher in non-university hospitals (13% versus 4%; P=0.01).
Resection in non-university hospitals was associated with higher postoperative
mortality (odds ratio 3.38, 95% confidence interval 1.37-10.68) and long-term
mortality (hazard ratio 1.21, 95% confidence interval 1.04-1.40). Sorafenib
treatment in non-university hospitals was also associated with higher long-term
mortality (hazard ratio 1.39, 95% confidence interval 1.06-1.82). Hospital volume
was not independent predictor for outcome. CONCLUSION: In low incidence
countries, outcome after resection or sorafenib for hepatocellular carcinoma may
differ between various hospital types.
PMID- 25846521
TI - ICU physician staffing: what else do we need to know?
PMID- 25846522
TI - COPD: undefeated!
PMID- 25846523
TI - Medical thoracoscopy: the green shapes of grey.
PMID- 25846524
TI - POINT: should radiation dose from CT scans be a factor in patient care? Yes.
PMID- 25846525
TI - COUNTERPOINT: should radiation dose from CT scans be a factor in patient care?
No.
PMID- 25846526
TI - Rebuttal from Dr McCunney.
PMID- 25846527
TI - Rebuttal from Dr Doss.
PMID- 25846528
TI - Systolic and mean pulmonary artery pressures: are they interchangeable in
patients with pulmonary hypertension?
AB - Pulmonary hypertension (PH) is a common complication of numerous diseases,
including left-sided heart diseases and chronic lung diseases and/or hypoxia,
where PH is associated with exercise limitation and a worse prognosis. Other
forms of PH include pulmonary arterial hypertension (PAH), chronic thromboembolic
PH (CTEPH), and PH with unclear multifactorial mechanisms. Over the past decade,
it has been documented that systolic pulmonary artery pressure (sPAP) may help
estimate mean pulmonary artery pressure (mPAP) in adults with high accuracy and
reasonably good precision (mPAP = 0.61 sPAP + 2 mm Hg). This strong linear
relationship between sPAP and mPAP was unexpected from a classic physiologic
point of view. Consistent results have been obtained from independent teams using
either high-fidelity micromanometer-tipped PA catheters or fluid-filled
catheters. Overall, the strong link between sPAP and mPAP has been documented
over a wide range of PAPs, heart rate, cardiac output, wedge pressure, and causes
of PH, during changes in posture and activity, and irrespective of patient's sex,
age, and BMI. A review of available invasive data confirms that patients with
CTEPH and idiopathic PAH matched for their mPAP exhibit essentially similar sPAP.
Pressure redundancy may be explained by the dependence of PA compliance upon
mPAP. The 25 mm Hg threshold used to define PH accurately corresponds to an sPAP
of 38 mm Hg. Although the limits of the echocardiographic estimation of sPAP are
widely documented, results from invasive studies may furnish an evidence-based
sPAP-derived mPAP value, potentially useful in the multiparameter
echocardiographic approach currently used to diagnose and follow patients with
PH.
PMID- 25846529
TI - Drug resistance in Mycobacterium tuberculosis: molecular mechanisms challenging
fluoroquinolones and pyrazinamide effectiveness.
AB - Physicians are more and more often challenged by difficult-to-treat cases of TB.
They include patients infected by strains of Mycobacterium tuberculosis that are
resistant to at least isoniazid and rifampicin (multidrug-resistant TB) or to at
least one fluoroquinolone (FQ) and one injectable, second-line anti-TB drug in
addition to isoniazid and rifampicin (extensively drug-resistant TB). The drug
treatment of these cases is very long, toxic, and expensive, and, unfortunately,
the proportion of unsatisfactory outcomes is still considerably high. Although
FQs and pyrazinamide (PZA) are backbone drugs in the available anti-TB regimens,
several uncertainties remain about their mechanisms of action and even more
remain about the mechanisms leading to drug resistance. From a clinical point of
view, a better understanding of the genetic basis of drug resistance will aid (1)
clinicians to provide quality clinical management to both drug-susceptible and
drug-resistant TB cases (while preventing emergence of further resistance), and
(2) developers of new molecular-based diagnostic assays to better direct their
research efforts toward a new generation of sensitive, specific, cheap, and easy
to-use point-of-care diagnostics. In this review we provide an update on the
molecular mechanisms leading to FQ- and PZA-resistance in M tuberculosis.
PMID- 25846530
TI - The uncommon case of Jahi McMath.
AB - A 13-year-old patient named Jahi McMath was determined to be dead by neurologic
criteria following cardiopulmonary arrest and resuscitation at a hospital in
Oakland, California. Her family did not agree that she was dead and refused to
allow her ventilator to be removed. The family's attorney stated in the media
that families, rather than physicians, should decide whether patients are dead
and argued in the courts that the families' constitutional rights of religion and
privacy would be violated otherwise. Ultimately, a judge agreed that the patient
was dead in keeping with California law, but the constitutional issue was
undecided. The patient was then transferred to a hospital in New Jersey, a state
whose laws allow families to require on religious grounds that death be
determined by cardiopulmonary criteria. Although cases such as this are uncommon,
they demonstrate public confusion about the concept of neurologic death and the
rejection of this concept by some families. The confusion may be caused in part
by a lack of uniformity in state laws regarding the legal basis of death, as
reflected in the differences between New Jersey and California statutes. Families
who reject the determination of death by neurologic criteria on religious grounds
should be given reasonable accommodation in all states, but society should not
pay for costly treatments for patients who meet these criteria unless the state
requires it, as only New Jersey does. Laws that give physicians the right to
determine death by neurologic criteria in other states probably can survive a
constitutional challenge. Physicians and hospitals faced with similar cases in
the future should follow state laws and work through the courts if necessary.
PMID- 25846531
TI - Capturing structured, pulmonary disease-specific data elements in electronic
health records.
AB - Electronic health records (EHRs) have the potential to improve health-care
quality by allowing providers to make better decisions at the point of care based
on electronically aggregated data and by facilitating clinical research. These
goals are easier to achieve when key, disease-specific clinical information is
documented as structured data elements (SDEs) that computers can understand and
process, rather than as free-text/natural-language narrative. This article
reviews the benefits of capturing disease-specific SDEs. It highlights several
design and implementation considerations, including the impact on efficiency and
expressivity of clinical documentation and the importance of adhering to data
standards when available. Pulmonary disease-specific examples of collection
instruments are provided from two commonly used commercial EHRs. Future
developments that can leverage SDEs to improve clinical quality and research are
discussed.
PMID- 25846532
TI - Air pollution exposure: a novel environmental risk factor for interstitial lung
disease?
AB - Air pollution exposure is a well-established risk factor for several adverse
respiratory outcomes, including airways diseases and lung cancer. Few studies
have investigated the relationship between air pollution and interstitial lung
disease (ILD) despite many forms of ILD arising from environmental exposures.
There are potential mechanisms by which air pollution could cause, exacerbate, or
accelerate the progression of certain forms of ILD via pulmonary and systemic
inflammation as well as oxidative stress. This article will review the current
epidemiologic and translational data supporting the plausibility of this
relationship and propose a new conceptual framework for characterizing novel
environmental risk factors for these forms of lung disease.
PMID- 25846533
TI - ICU director data: using data to assess value, inform local change, and relate to
the external world.
AB - Improving value within critical care remains a priority because it represents a
significant portion of health-care spending, faces high rates of adverse events,
and inconsistently delivers evidence-based practices. ICU directors are
increasingly required to understand all aspects of the value provided by their
units to inform local improvement efforts and relate effectively to external
parties. A clear understanding of the overall process of measuring quality and
value as well as the strengths, limitations, and potential application of
individual metrics is critical to supporting this charge. In this review, we
provide a conceptual framework for understanding value metrics, describe an
approach to developing a value measurement program, and summarize common metrics
to characterize ICU value. We first summarize how ICU value can be represented as
a function of outcomes and costs. We expand this equation and relate it to both
the classic structure-process-outcome framework for quality assessment and the
Institute of Medicine's six aims of health care. We then describe how ICU leaders
can develop their own value measurement process by identifying target areas,
selecting appropriate measures, acquiring the necessary data, analyzing the data,
and disseminating the findings. Within this measurement process, we summarize
common metrics that can be used to characterize ICU value. As health care, in
general, and critical care, in particular, changes and data become more
available, it is increasingly important for ICU leaders to understand how to
effectively acquire, evaluate, and apply data to improve the value of care
provided to patients.
PMID- 25846535
TI - An addition was made to the abstract: the association of direct thrombin
inhibitor anticoagulants with cardiac thromboses.
PMID- 25846536
TI - Diffuse alveolar damage in a patient receiving dronedarone.
AB - Dronedarone is an amiodarone-like antiarrhythmic with a modified structure. The
addition of a methyl sulfonyl group theoretically reduces the toxicity of
amiodarone, specifically, adverse thyroid and pulmonary effects. Although animal
studies have implicated dronedarone as a cause of lung injury, to date controlled
trials in humans have not demonstrated an association. A 68-year-old woman
developed a dry cough and worsening respiratory distress after receiving
dronedarone for 6 months. Discontinuation of dronedarone therapy and subsequent
steroid therapy led to a dramatic improvement of symptoms. Dronedarone may be
associated with interstitial lung disease. We believe that patients receiving
dronedarone should have their diffusing capacity of lung for carbon monoxide and
lung volumes monitored prior to initiation of therapy and frequently thereafter.
PMID- 25846537
TI - Isolated pauciimmune pulmonary capillaritis successfully treated with rituximab.
AB - Diffuse alveolar hemorrhage (DAH) is a syndrome caused by different mechanisms,
including capillary stress failure, diffuse alveolar damage, and capillaritis.
Capillaritis is the most common cause and is often associated with systemic
autoimmune disorders, most commonly antineutrophilic cytoplasmic antibody
associated vasculitis. The occurrence of DAH with underlying pulmonary
capillaritis but without clinical or serologic findings of an associated
underlying systemic disorder is known as isolated pauciimmune pulmonary
capillaritis (IPPC), and only eight cases have been described in the literature.
The mainstay of treatment of this rare condition has been cyclophosphamide and
glucocorticoids. When cases are unresponsive to cyclophosphamide, there is no
known alternative treatment. Herein, we describe a case of IPPC that failed
cyclophosphamide treatment with recurrent DAH. Rituximab therapy was then
initiated with no further evidence of recurrence. This case report suggests that
rituximab could be considered an alternative therapy to induce remission in
patients with IPPC.
PMID- 25846534
TI - The pathophysiology of insomnia.
AB - Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity
or quality that is associated with difficulty falling asleep, frequent nighttime
awakenings with difficulty returning to sleep, and/or awakening earlier in the
morning than desired. Although progress has been made in our understanding of the
nature, etiology, and pathophysiology of insomnia, there is still no universally
accepted model. Greater understanding of the pathophysiology of insomnia may
provide important information regarding how, and under what conditions, the
disorder develops and is maintained as well as potential targets for prevention
and treatment. The aims of this report are (1) to summarize current knowledge on
the pathophysiology of insomnia and (2) to present a model of the pathophysiology
of insomnia that considers evidence from various domains of research. Working
within several models of insomnia, evidence for the pathophysiology of the
disorder is presented across levels of analysis, from genetic to molecular and
cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior,
and self-report. We discuss the role of hyperarousal as an overarching theme that
guides our conceptualization of insomnia. Finally, we propose a model of the
pathophysiology of insomnia that integrates the various types of evidence
presented.
PMID- 25846538
TI - A 66-year-old woman with fever, cough, and a tongue lesion.
AB - A 66-year-old woman presented with acute onset of fever, chills, and productive
cough associated with right-sided chest pain. During a recent hospitalization for
dyspnea, she had been diagnosed with Coombs-positive autoimmune hemolytic anemia
and had been taking a tapering dose of prednisone starting approximately 6 weeks
prior to admission. In the interim, her dyspnea had resolved on treatment with
steroids. At the time of presentation, her prednisone dose was 40 mg. Additional
medical history included VTE, for which the patient was receiving anticoagulation
therapy, and steroid-induced diabetes mellitus. Many years earlier, she had been
treated for TB in her home country. The patient had immigrated to Queens, New
York, from a Nepalese village 8 years prior. While still in Nepal, she had worked
on a farm and had been in close proximity to cows. In Queens, she lived with her
family in a house with a small garden but had no pets. Recent travel included a
visit to Nepal 9 months ago and a trip to Syracuse, New York, one month prior to
presentation. She was a never smoker and did not consume alcohol.
PMID- 25846539
TI - A 15-year-old boy with snoring and molar tooth sign.
AB - A 15-year-old boy presented for evaluation of snoring and sleep-disordered
breathing. The parents noted that the patient snored every night and that he had
episodes when he stopped breathing, ending with gasping for air. He had no
history of sleep walking, night terrors, tongue biting, or seizures. The patient
had two healthy siblings, but he had a history of intellectual disability and
developmental delay. The patient had a history of adenotonsillectomy.
PMID- 25846540
TI - A 3-month-old infant with recurrent apparent life-threatening events in a car
seat.
AB - A 3-month-old infant was brought to clinic for evaluation of recurrent apparent
life-threatening events (ALTEs). Two ALTE episodes occurred while the infant was
sleeping in a safety car seat. The first one occurred when he was 4 weeks old.
His mother noticed that he was not breathing; he appeared limp with full body
cyanosis. His mother picked him up from the car seat, and he started breathing
spontaneously and without any sign of distress. His skin color returned to
normal. He was evaluated at the ED where the physical examination was normal. He
was hospitalized 1 day for observation. During this time, workup, including ECG
and chest radiograph, was normal. The parents were instructed on
cardiorespiratory resuscitation and recommended to change car seats. The infant
was discharged with an apnea monitor. He wore the apnea monitor while in the car
seat. A second similar episode occurred at 10 weeks of age for which he was seen
at the ED and referred to our clinic for further evaluation. Neither episode was
related to feeding.
PMID- 25846541
TI - The critical flaw in physician compensation is not the sustainable growth rate!
PMID- 25846542
TI - Response.
PMID- 25846543
TI - How is TB transmitted?
PMID- 25846544
TI - Response.
PMID- 25846545
TI - Idiopathic pulmonary arterial hypertension in Asians: a long-term study on
clinical outcomes.
PMID- 25846546
TI - Racial and sex differences in presentation and outcomes of small cell lung cancer
in the United States: 1973 to 2010.
PMID- 25846548
TI - Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with
new onset diabetes: a nationwide cohort study.
AB - BACKGROUND: Diabetes increases the risk of hepatocellular carcinoma (HCC),
however, the time-relationship between hepatitis B virus and diabetes for the
development of HCC remains unclear. AIM: To explore the risk of HCC in chronic
hepatitis B patients with newly diagnosed diabetes. METHODS: We conducted a
nationwide cohort study by using Taiwanese National Health Insurance Research
Database, which covers over 99% of entire population. Among randomly sampled one
million enrollees, 14 523 chronic hepatitis B patients were diagnosed in years
1997-2009. We defined new onset diabetes as patients who were given the diagnosis
in the years 1999-2009, but not in 1997-1998. The cohorts of chronic hepatitis B
with new onset diabetes (n = 2099) and 1:1 ratio age-, gender- and inception
point (onset date of diabetes)- matched nondiabetes (n = 2080) were followed up
from the inception point until development of HCC, withdrawal from insurance or
December 2009. RESULTS: After adjustment for competing mortality, patients with
new onset diabetes had a significantly higher cumulative incidence of HCC
[relative risk = 1.628, 95% confidence interval (CI) = 1.114-2.378, modified log
rank test, P = 0.012] as compared to nondiabetes patients. After adjustment for
age, gender, hyperlipidaemia, chronic hepatitis B treatment, statins therapy,
cirrhosis, comorbidity index and obesity, diabetes was still an independent
predictor for HCC (hazard ratio = 1.798, 95% CI = 1.194-2.707, P = 0.005).
CONCLUSION: Chronic hepatitis B patients with newly diagnosed diabetes have an
increased risk of hepatocellular carcinoma over time.
PMID- 25846547
TI - Patients with reduced heart rate response to adenosine infusion have low
myocardial flow reserve in (13)N-ammonia PET studies.
AB - To assess the effect of adenosine infusion by evaluating the relationship between
heart rate (HR) response to adenosine and myocardial flow reserve (MFR) of remote
regions supplied by normal coronary arteries in (13)N-ammonia PET. Thirty-one
consecutive subjects (20 known coronary artery disease patients, 4 chronic heart
failure patients, and 7 normal volunteers) except cases having 3-vessel disease
underwent rest and adenosine stress (13)N-ammonia myocardial perfusion PET. Semi
quantitative, quantitative, and gated analyses were performed. Subjects were
divided into two groups with regard to HR response to adenosine. Twenty-two
subjects had normal HR response (peak/rest HR > 1.20), while reduced HR response
(<= 1.20) was observed in nine subjects. There were no differences in rest
myocardial blood flow (MBF) of remote regions between the groups. Subjects with
reduced HR response had significantly lower stress MBF and MFR of remote regions
than those with normal HR response (stress MBF: 1.559 +/- 0.517 vs. 2.279 +/-
0.530, p = 0.004, MFR: 1.59 +/- 0.36 vs. 2.35 +/- 0.53, p = 0.001). There were no
significant differences between the groups by means of semi-quantitative scoring.
Rest and stress ejection fraction (EF) in the reduced HR response group was lower
than that in the normal HR response group. In a multiple stepwise regression
analysis, HR ratio, dyslipidemia, and Brinkman index were identified as
predictors of the change in MFR of remote regions. Subjects with reduced HR
response to adenosine had lower stress MBF and MFR of remote regions and lower
EF. Moreover, HR response was one of the predictors of the change in MFR of
remote regions.
PMID- 25846549
TI - Therapeutic Use of Music and Television in Neurocritical Care: A Practice Survey.
AB - INTRODUCTION: Although health care providers often play music via radio, or play
television, to calm and soothe patients, limited research is available to guide
practice. METHOD: This study used a 17-item practice survey that was distributed
electronically to neurocritical care society members in July 2014. Responses were
collated and analyzed using SAS (Version 9.3). RESULTS: There were 118 completed
responses, including from 71 attending physicians, 9 resident or fellow
physicians, 30 nurses, and 8 affiliate professional members. The majority of
respondents sometimes or always play music (65%) and agree that music is
therapeutic (70%). However, there was no clear practice pattern regarding when or
why music or TV should be used as an intervention in the neurocritical care unit.
CONCLUSION: The use of music and TV is a common intervention in the neurocritical
care unit but lacks a strong scientific foundation and is associated with a high
practice variance.
PMID- 25846550
TI - Snack and Relax(r): A Strategy to Address Nurses' Professional Quality of Life.
AB - PURPOSE AND DESIGN: Snack and Relax(r) (S&R), a program providing healthy snacks
and holistic relaxation modalities to hospital employees, was evaluated for
immediate impact. A cross-sectional survey was then conducted to assess the
professional quality of life (ProQOL) in registered nurses (RNs); compare S&R
participants/nonparticipants on compassion satisfaction (CS), burnout, and
secondary traumatic stress (STS); and identify situations in which RNs
experienced compassion fatigue or burnout and the strategies used to address
these situations. METHOD: Pre- and post vital signs and self-reported stress were
obtained from S&R attendees (N = 210). RNs completed the ProQOL Scale measuring
CS, burnout, and STS (N = 158). FINDINGS: Significant decreases in self-reported
stress, respirations, and heart rate were found immediately after S&R. Low CS was
noted in 28.5% of participants, 25.3% had high burnout, and 23.4% had high STS.
S&R participants and nonparticipants did not differ on any of the ProQOL scales.
Situations in which participants experienced compassion fatigue/burnout were
categorized as patient-related, work-related, and personal/family-related.
Strategies to address these situations were holistic and stress reducing.
CONCLUSION: Providing holistic interventions such as S&R for nurses in the
workplace may alleviate immediate feelings of stress and provide a moment of
relaxation in the workday.
PMID- 25846551
TI - Profiling cancer gene mutations in longitudinal epithelial ovarian cancer
biopsies by targeted next-generation sequencing: a retrospective study.
AB - BACKGROUND: The majority of patients with stage III-IV epithelial ovarian cancer
(EOC) relapse after initially responding to platinum-based chemotherapy, and
develop resistance. The genomic features involved in drug resistance are unknown.
To unravel some of these features, we investigated the mutational profile of
genes involved in pathways related to drug sensitivity in a cohort of matched
tumors obtained at first surgery (Ft-S) and second surgery (Sd-S). PATIENTS AND
METHODS: Matched biopsies (33) taken at Ft-S and Sd-S were selected from the
'Pandora' tumor tissue collection. DNA libraries for 65 genes were generated
using the TruSeq Custom Amplicon kit and sequenced on MiSeq (Illumina). Data were
analyzed using a high-performance cluster computing platform (Cloud4CARE project)
and independently validated. RESULTS: A total of 2270 somatic mutations were
identified (89.85% base substitutions 8.19% indels, and 1.92% unknown).
Homologous recombination (HR) genes and TP53 were mutated in the majority of Ft
S, while ATM, ATR, TOP2A and TOP2B were mutated in the entire dataset. Only 2% of
mutations were conserved between matched Ft-S and Sd-S. Mutations detected at
second surgery clustered patients in two groups characterized by different
mutational profiles in genes associated with HR, PI3K, miRNA biogenesis and
signal transduction. CONCLUSIONS: There was a low level of concordance between Ft
S and Sd-S in terms of mutations in genes involved in key processes of tumor
growth and drug resistance. This result suggests the importance of future
longitudinal analyses to improve the clinical management of relapsed EOC.
PMID- 25846553
TI - Reply to the letter to the editor 'potential clinical relevant drug-drug
interactions: comparison between different compendia, do we have a validated
method?' by Conde-Estevez et al.
PMID- 25846552
TI - Sunitinib 2 weeks on, 1 off: strengths and weaknesses.
PMID- 25846555
TI - Alternative sunitinib schedules in metastatic renal cell carcinoma and the
RAINBOW study.
PMID- 25846554
TI - High level of chromosomal instability in circulating tumor cells of ROS1
rearranged non-small-cell lung cancer.
AB - BACKGROUND: Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine
kinase gene have been reported in a small subset of patients with non-small-cell
lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could
be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of
CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. PATIENTS AND METHODS:
Using isolation by size of epithelial tumor cells (ISET) filtration and filter
adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was
examined in CTCs from four ROS1-rearranged patients treated with the ROS1
inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations
observed in CTCs at baseline from ROS1-rearranged patients were compared with
those present in tumor biopsies and in CTCs during crizotinib treatment.
Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content
quantification and chromosome enumeration. RESULTS: ROS1 rearrangement was
detected in the CTCs of all four patients with ROS1 rearrangement previously
confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1
rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1
negative patients, median background hybridization of ROS1-rearranged CTCs was
7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy
number, was significantly higher in baseline CTCs compared with paired tumor
biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in
ROS1-rearranged CTCs increased significantly in two patients who progressed
during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a
high DNA content and gain of chromosomes, indicating high levels of aneuploidy
and numerical CIN. CONCLUSION: We provide the first proof-of-concept that CTCs
can be used for noninvasive and sensitive detection of ROS1 rearrangement in
NSCLC patients. CTCs from ROS1-rearranged patients show considerable
heterogeneity of ROS1-gene abnormalities and elevated numerical CIN, a potential
mechanism to escape ROS1-inhibitor therapy in ROS1-rearranged NSCLC tumors.
PMID- 25846556
TI - Single active-site mutants are sufficient to enhance serine:pyruvate alpha
transaminase activity in an omega-transaminase.
AB - We have analyzed the natural evolution of transaminase structure and sequence
between an alpha-transaminase serine-pyruvate aminotransferase and an omega
transaminase from Chromobacterium violaceum with < 20% sequence identity, and
identified the active-site regions that are least conserved structurally. We also
show that these structural changes correlate strongly with transaminase substrate
specificity during evolution and therefore might normally be presumed to be
essential determinants of substrate specificity. However, key residues are often
conserved spatially during evolution and yet originate from within a different
region of the sequence via structural reorganizations. In the present study, we
also show that alpha-transaminase-type serine-pyruvate aminotransferase activity
can be engineered into the CV2025 omega-transaminase scaffold with any one of
many possible single-point mutations at three key positions, without the
requirement for significant backbone remodeling, or repositioning of the residue
from a different region of sequence. This finding has significant implications
for enzyme redesign in which solutions to substrate specificity changes may be
found more efficiently than is achieved by engineering in all sequence and
structure determinants identified by correlation to substrate specificity.
PMID- 25846557
TI - Cost attributable to Fetal Alcohol Spectrum Disorder in the Canadian correctional
system.
AB - Prenatal alcohol exposure is the leading identifiable cause of intellectual
disability in the Western world and may result in Fetal Alcohol Spectrum Disorder
(FASD). Individuals with FASD have a higher risk of being involved in the legal
system, either as offenders or as victims. Therefore, the aim of the current
study was to estimate the direct cost for youths (12-17 years old) and adults
(18+ years old) with FASD to the Canadian correctional system in 2011/2012. The
prevalence of FASD in the Canadian correctional system, obtained from the current
epidemiological literature, was applied to the average number of youths and
adults in the correctional system in 2011/2012. The average daily cost for
corrections was then applied to the estimated number of youths and adults with
FASD in custody. The cost of corrections among youths with FASD in Canada in
2011/2012 was calculated to be approximately $17.5M Canadian dollars (CND; $13.6M
CND for males and $3.8M CND for females) and among adults with FASD was estimated
to be about $356.2M CND ($140M CND for provincial and territorial custody and
$216.2M CND for federal custody). The study findings emphasize the need to raise
awareness regarding the prevalence of FASD in the correctional system. It is
crucial to incorporate FASD screening and intervention strategies as early as
possible in the criminal justice process.
PMID- 25846558
TI - Seclusion and the importance of contextual factors: An innovation project
revisited.
AB - Variation in seclusion rates between psychiatric facilities cannot be adequately
explained by patient characteristics alone and there is a growing awareness of
the influence of 'cultural' and staff factors on the use of seclusion. In this
study, staff variables as well as seclusion parameters were investigated during
the implementation of an innovation project, against the background of an
institutional program to reduce the use of coercive measures. The results
demonstrate the impact of confidence within the team, staffing level and
communication with the patient on nurses' decisions on seclusion. The importance
of the organizational context is further illustrated by the negative effects of
organizational instability on nurses' attitudes and decision making with respect
to seclusion, and on seclusion rates. A reduction in the use of seclusion was
achieved after the implementation of the innovation project; however, during a
period of organizational turmoil, the work engagement scores of staff decreased
and the use of seclusion increased. The results of this study show the
vulnerability of innovations within the continuously changing organizational
context of mental health care.
PMID- 25846559
TI - Virus disease in wheat predicted to increase with a changing climate.
AB - Current atmospheric CO2 levels are about 400 MUmol mol(-1) and are predicted to
rise to 650 MUmol mol(-1) later this century. Although the positive and negative
impacts of CO2 on plants are well documented, little is known about interactions
with pests and diseases. If disease severity increases under future environmental
conditions, then it becomes imperative to understand the impacts of pathogens on
crop production in order to minimize crop losses and maximize food production.
Barley yellow dwarf virus (BYDV) adversely affects the yield and quality of
economically important crops including wheat, barley and oats. It is transmitted
by numerous aphid species and causes a serious disease of cereal crops worldwide.
This study examined the effects of ambient (aCO2 ; 400 MUmol mol(-1) ) and
elevated CO2 (eCO2 ; 650 MUmol mol(-1) ) on noninfected and BYDV-infected wheat.
Using a RT-qPCR technique, we measured virus titre from aCO2 and eCO2 treatments.
BYDV titre increased significantly by 36.8% in leaves of wheat grown under eCO2
conditions compared to aCO2 . Plant growth parameters including height, tiller
number, leaf area and biomass were generally higher in plants exposed to higher
CO2 levels but increased growth did not explain the increase in BYDV titre in
these plants. High virus titre in plants has been shown to have a significant
negative effect on plant yield and causes earlier and more pronounced symptom
expression increasing the probability of virus spread by insects. The combination
of these factors could negatively impact food production in Australia and
worldwide under future climate conditions. This is the first quantitative
evidence that BYDV titre increases in plants grown under elevated CO2 levels.
PMID- 25846560
TI - Tau immunotherapy for Alzheimer's disease.
AB - Targeting pathological tau protein in Alzheimer's disease (AD) and related
tauopathies has shown great potential in animal models. Given that tau lesions
correlate better with the degree of dementia than do amyloid-beta (Abeta)
plaques, their clearance may be clinically more efficacious than removing Abeta
when cognitive deficits become evident in AD. Several complementary mechanisms of
antibody-mediated removal of tau aggregates are likely to act in concert and the
importance of each one may depend on antibody properties, the disease, and its
stage. Clinical trials of tau immunotherapy are already underway and several more
are likely to be initiated in the near future.
PMID- 25846561
TI - Obesity depresses baroreflex control of renal sympathetic nerve activity and
heart rate in Sprague Dawley rats: role of the renal innervation.
AB - AIM: This study investigated the role of the renal innervation in arterial and
cardiopulmonary baroreflex regulation of renal sympathetic nerve activity (RSNA)
and heart rate (HR) in rats fed a high-fat diet to induce obesity. METHODS: Rats
received either a normal (12% kcal) or high (45% kcal) fat diet for 60 days. On
day 61, rats were anesthetized and prepared for recording left RSNA. In one
group, the renal nerves remained intact, while in the other, both kidneys were
denervated. Baroreflex gain curves for RSNA and HR were generated by increasing
and decreasing blood pressure. Low-pressure baroreceptors were challenged by
infusing a saline load. RESULTS: Mean blood pressure was 135 mmHg in the fat-fed
and 105 mmHg (P < 0.05) in normal rats. Weight gain, adiposity index and
creatinine clearance were 37, 82 and 55% higher (P < 0.05-0.001), but urine flow
rate and fractional sodium excretions were 53 and 65% (both P < 0.001) lower,
respectively, in the fat-fed compared to normal rats. In fat-fed rats with
innervated kidneys, RSNA and HR arterial baroreflex sensitivities were reduced by
73 and 72% (both P < 0.05) but were normal in renally denervated rats. Volume
expansion decreased RSNA by 66% (P < 0.001) in normal rats, but not in the intact
fat-fed rats and by 51% (P < 0.01) in renally denervated fat-fed rats.
CONCLUSION: Feeding a high-fat diet caused hypertension associated with
dysregulation of the arterial and cardiopulmonary baroreflexes which was
dependent on an intact renal innervation. This suggests that in obese states
neural signals arising from the kidney contribute to a deranged autonomic
control.
PMID- 25846562
TI - Goldberg-Shprintzen megacolon syndrome with associated sensory motor axonal
neuropathy.
AB - Goldberg-Shprintzen megacolon syndrome (GOSHS) (OMIM 609460) is characterized by
a combination of learning difficulties, characteristic dysmorphic features and
Hirschsprung's disease. Variable clinical features include iris coloboma,
congenital heart defects and central nervous system abnormalities, in particular
polymicrogyria. GOSHS has been attributed to recessive mutations in KIAA1279,
encoding kinesin family member (KIF)-binding protein (KBP) with a crucial role in
neuronal microtubule dynamics. Here we report on a 7-year-old girl with GOSHS as
a result of a homozygous deletion of exons 5 and 6 of the KIAA1279 gene. She had
been referred with the suspicion of an underlying neuromuscular disorder before
the genetic diagnosis was established, prompted by the findings of motor
developmental delay, hypotonia, ptosis and absent reflexes. Neurophysiological
studies revealed unequivocal evidence of a peripheral axonal sensory motor
neuropathy. We hypothesize that an axonal sensory motor neuropathy may be part of
the phenotypical spectrum of KIAA1279-related GOSHS, probably reflecting the
effects of reduced KBP protein expression on peripheral neuronal function.
PMID- 25846563
TI - Signal transducers and activators of transcription 3-induced metastatic potential
in gastric cancer cells is enhanced by glycogen synthase kinase-3beta.
AB - The transcription factor signal transducers and activators of transcription 3
(STAT3) can promote cancer metastasis, but its underlying regulatory mechanisms
in gastric cancer cell invasiveness still remain obscure. We investigated the
relationship between STAT3 and glycogen synthase kinase-3beta (GSK-3beta) and its
significance in metastatic potential in gastric cancer cells. Immunohistochemical
tissue array analysis of 267 human gastric carcinoma specimens showed that the
expressions of active forms of STAT3 (pSTAT3) and GSK-3beta (pGSK-3beta) were
found in 68 (25%) and 124 (46%) of 267 gastric cancer cases, respectively,
showing a positive correlation (p < 0.001). Cell culture experiments using
gastric cancer cell lines SNU-638 and SNU-668 revealed that STAT3 suppression did
not affect pGSK-3beta expression, whereas GSK-3beta inhibition reduced pSTAT3
expression. With respect to metastatic potential in gastric cancer cells, both
STAT3 suppression and GSK-3beta inhibition decreased cell migration, invasion,
and mesenchymal marker (Snail, Vimentin, and MMP9) expression. Moreover, the
inhibitory effects of STAT3 and GSK-3beta on cell migration were synergistic.
These results demonstrated that STAT3 and GSK-3beta are positively associated and
synergistically contribute to metastatic potential in gastric cancer cells. Thus,
dual use of STAT3 and GSK-3beta inhibitors may enhance the efficacy of the anti
metastatic treatment of gastric cancer.
PMID- 25846564
TI - Aspergillus nidulans flippase DnfA is cargo of the endocytic collar and plays
complementary roles in growth and phosphatidylserine asymmetry with another
flippase, DnfB.
AB - Endocytosis and exocytosis are strictly segregated at the ends of hyphal cells of
filamentous fungi, with a collar of endocytic activity encircling the growing
cell tip, which elongates through directed membrane fusion. It has been proposed
that this separation supports an endocytic recycling pathway that maintains polar
localization of proteins at the growing apex. In a search for proteins in the
filamentous fungus Aspergillus nidulans that possess an NPFxD motif, which
signals for endocytosis, a Type 4 P-Type ATPase was identified and named DnfA.
Interestingly, NPFxD is at a different region of DnfA than the same motif in the
Saccharomyces cerevisiae ortholog, although endocytosis is dependent on this
motif for both proteins. DnfA is involved in asexual sporulation and polarized
growth. Additionally, it is segregated within the Spitzenkorper from another Type
4 P-type ATPase, DnfB. Next, the phosphatidylserine marker GFP::Lact-C2 was
expressed in growing hyphae, which revealed that this phospholipid is enriched on
the cytosolic face of secretory vesicles. This distribution is affected by
deleting either dnfA or dnfB. These findings provide evidence for the spatial and
temporal segregation of Type4-ATPases in filamentous fungi, and the asymmetric
distribution of phosphatidylserine to the Spitzenkorper in A. nidulans.
PMID- 25846565
TI - TDP-43 in amyotrophic lateral sclerosis - is it a prion disease?
AB - Amyotrophic lateral sclerosis is a devastating disease characterized by rapidly
progressive paresis. The neuropathological hallmark of most amyotrophic lateral
sclerosis cases are neuronal and glial aggregates of phosphorylated 43-kDa TAR
DNA-binding protein (pTDP-43). The accumulation of similar proteins into
insoluble aggregates is now recognized as a common pathological hallmark of
neurodegenerative diseases in general. Importantly, many of these proteins such
as tau and amyloid-beta in Alzheimer's disease and alpha-synuclein in Parkinson's
show a stereotypical sequential distribution pattern with progressing disease. In
this review, we discuss recent evidence that TDP-43 in ALS may propagate
similarly to other neurodegenerative disease proteins. We furthermore delineate
similarities and important differences of TDP-43 proteinopathies to prion
diseases.
PMID- 25846566
TI - Non-paraneoplastic ataxia in a patient with contactin-associated protein-2
antibodies and benign course.
PMID- 25846567
TI - Reversible cerebral vasoconstriction syndrome triggered by an electronic
cigarette: case report.
PMID- 25846569
TI - Diagnostic utility of microarray testing in pregnancy loss.
AB - OBJECTIVES: To determine the frequency of clinically significant chromosomal
abnormalities identified by chromosomal microarray in pregnancy losses at any
gestational age and to compare microarray performance with that of traditional
cytogenetic analysis when testing pregnancy losses. METHODS: Among 535 fetal
demise specimens of any gestational age, clinical microarray-based comparative
genomic hybridization (aCGH) was performed successfully on 515, and a subset of
107 specimens underwent additional single nucleotide polymorphism (SNP) analysis.
RESULTS: Overall, clinically significant abnormalities were identified in 12.8%
(64/499) of specimens referred with normal or unknown karyotypes. Detection rates
were significantly higher with earlier gestational age. In the subset with normal
karyotype, clinically significant abnormalities were identified in 6.9% (20/288).
This detection rate did not vary significantly with gestational age, suggesting
that, unlike aneuploidy, the contribution of submicroscopic chromosomal
abnormalities to fetal demise does not vary with gestational age. In the 107
specimens that underwent aCGH and SNP analysis, seven cases (6.5%) had
abnormalities of potential clinical significance detected by the SNP component,
including female triploidy. aCGH failed to yield fetal results in 8.3%, which is
an improvement over traditional cytogenetic analysis of fetal demise specimens.
CONCLUSIONS: Both the provision of results in cases in which karyotype fails and
the detection of abnormalities in the presence of a normal karyotype demonstrate
the increased diagnostic utility of microarray in pregnancy loss. Thus,
chromosomal microarray testing is a preferable, robust method of analyzing cases
of pregnancy loss to better delineate possible genetic etiologies, regardless of
gestational age.
PMID- 25846570
TI - A study on the status of inflammatory systems in camels naturally infected with
Toxoplasma gondii.
AB - Toxoplasma gondii is a unique intracellular parasite with a worldwide
distribution. This parasite infects a variety of cells in a wide range of animal
species such as dromedary camels (Camelus dromedarius). In order to evaluate the
pattern of possible changes in the blood level of some inflammatory mediators and
antioxidant enzymes in camels infected with T. gondii, blood samples were taken
from a total of 493 dromedary camels and serum concentrations of inflammatory
mediators, acute phase proteins and antioxidant enzymes were measured. According
to serological data, no seropositivity was found for anti-T. gondii IgM in serum
samples; however, 49 camels (9.93 %) showed positive titrations for anti
Toxoplasma IgG. The analyses of data in seropositive animals showed significant
increases (P < 0.05) in the serum level of IL-1beta and adenosine deaminase
activity; however, IFN-gamma and TNF-alpha demonstrated no significant changes in
serum samples of the infected camels. In addition, while major acute phase
proteins (haptoglobin (Hp) and serum amyloid A (SAA)) were markedly elevated in
infected camels, the activity of antioxidant enzymes (SOD and GPX) was remarkably
decreased in the blood samples of infected animals. Thus, during the chronic
infection in camels, T. gondii can promote significant rises in concentrations of
some cytokines (such as IL-1beta), acute phase proteins and adenosine deaminase.
PMID- 25846571
TI - A duplex PCR-based assay for simultaneous detection of Trypanosoma evansi and
Theileria annulata infections in water buffaloes.
AB - Trypanosomosis and bovine tropical theileriosis are important vector-borne
protozoan diseases imposing some of the serious constraints on the health and
productivity of domestic cattle in tropical and subtropical regions of the world.
Following recovery from primary infection of both these conditions, animals
become persistent carriers and act as reservoirs of infection thereby playing a
critical role in disease epidemiology. The present study describes development
and evaluation of duplex polymerase chain reaction (PCR) assays for simultaneous
detection of Trypanosoma evansi and Theileria annulata in buffaloes. Following in
silico screening for candidate target genes representing each of the pathogens,
an optimized duplex PCR assay was established using TBR F/R and TAMS F/R as
primer sets encoding for products of 164 and 721 bp for T. evansi and T.
annulata, respectively. The results were compared and correlated with
conventional Giemsa-stained thin blood smear examination and the single PCR
assay. The duplex PCR detected each pathogen with the same level of sensitivity,
irrespective of whether its DNA was amplified in isolation or together with DNA
of another pathogen. Moreover, single and duplex PCRs were able to detect each
species with equal sensitivity in serially diluted DNA representing mixtures of
T. evansi and T. annulata, and no evidence of nonspecific amplification from
nontarget species was observed. The developed assay may be seen as a good tool
for epidemiological studies aiming at assessing the burden of dual infections and
improving control of the associated diseases in endemic regions.
PMID- 25846572
TI - Effect of different levels of raw and heated grass pea seed (Lathyrus sativus) on
nutrient digestibility, intestinal villus morphology and growth performance of
broiler chicks.
AB - This study aimed to investigate chemical composition and effect of different
levels (0%, 10% and 20%) of raw grass pea (RGP) and heat-treated (120 degrees C
for 30 min) grass pea seed (HGP) on nutrient digestibility, dressing percentage,
relative internal organ weights, intestinal villous morphology and broiler
chicks' performance. A total number of 200 day-old male chicks were raised under
similar condition for 10 days. On day 11, chicks were randomly assigned to five
dietary treatments and four replicates of 10 birds each. The result of chemical
analysis indicated that Iranian grass pea seed has low levels of total and
condensed tannin, and it may be considered as a good source of protein (36.1%)
and energy (17.09 kJ GE/g). Heat treatment reduced (p < 0.05) the total and
condensed tannin to 21% and 78% respectively. Grass peas seed had higher levels
of nitrogen-free extract, P, Na, Mg and Zn than soya bean meal. The apparent
digestibility of gross energy and lipid was affected (p < 0.01) by the treatment
diets, and it was the lowest after feeding 20% of HGP (p < 0.05). The relative
weight of breast and pancreas (p < 0.05) was affected by treatments. Percentage
weight of breast and pancreas increased (p < 0.05) after feeding high levels
(20%) of RGP and HGP. Substitution of 20% of RGP and HGP increased the duodenal
crypt depth (p < 0.05); however, it had no suppressive effect on villus height as
the absorptive surface of intestine. The feed conversion ratio was not affected
by the treatments in the total experimental period. This study showed that,
although the high level of grass pea seed caused a remarkable increase in the
relative weight of pancreas and decreased the apparent digestibility of gross
energy and lipid, it had beneficial effect on breast relative weight. It seems
that heat processing is not effective method for improving quality of Iranian
grass pea seed.
PMID- 25846573
TI - Patient Education vs. Patient Experiences of Self-advocacy: Changing the
Discourse to Support Cancer Survivors.
AB - A growing emphasis on patient self-advocacy has emerged in the public discourse
on cancer survivorship. This discourse shapes patients' conceptualizations about
self-advocacy and in turn influences their health care attitudes and behaviors.
The purpose of this discourse analysis is to explore the language of self
advocacy by comparing a published self-advocacy guide with the lived experiences
of women with ovarian cancer. Data sources include (1) a self-advocacy patient
education guide published by the National Coalition for Cancer Survivorship and
(2) transcripts of focus groups conducted with ovarian cancer survivors.
Discourse analysis techniques were used to take a close look at the language used
by both to uncover the meaning each group ascribed to self-advocacy. Challenges
and inconsistencies were noted between the patient education guide and
transcripts including viewing self-advocacy as a skill set to assert one's needs
as opposed to a means by which to preserve a positive attitude and maintain a
trusting relationship with health care providers, respectively. Some women saw
themselves as self-advocates yet struggled to locate relevant health information
and hesitated to upset their relationship with their health care providers. This
analysis highlights tensions between the discourses and points to ways in which
patient education materials can be adjusted to support cancer survivors in
advocating for their needs according to their unique situations and preferences.
PMID- 25846575
TI - The effect of drug use disorder onset, remission or persistence on an
individual's personal social network.
AB - BACKGROUND AND OBJECTIVES: Drug use disorders (DUD) have strong associations with
numerous social problems. However, little is known concerning differences between
individuals who experience DUD onset, persistence or remission. While the
literature is fairly clear on who is most likely to experience DUD onset and
persistence, many correlates of DUD remission, including personal social
networks, lack the empirical foundation to utilize them in evidence-based
intervention or prevention efforts. While small, community samples suggest DUD
remission is associated with growth in personal social networks, this conclusion
is in need of larger population studies to justify. METHODS: This study used
Waves 1 and 2 of the National Epidemiologic Study on Alcohol and Related
Conditions (NESARC) to examine whether DUD status is a correlate of personal
social networks. RESULTS: Multivariate models showed DUD onset and DUD
persistence were related to smaller personal social networks. However,
individuals who experience DUD remission showed personal social networks similar
to persons who never experienced a DUD. DISCUSSION AND CONCLUSIONS: As one of the
first empirical studies of personal social networks among individuals with
different stages of DUD using nationally representative data, these findings
suggest that by decreasing drug use, personal social networks may be increased,
which is a strong trait associated with the social influence necessary with
maintaining DUD recovery.
PMID- 25846574
TI - Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation
switch.
AB - Human cytomegalovirus (HCMV) is a highly prevalent pathogen that induces life
long infections notably through the establishment of latency in hematopoietic
stem cells (HSC). Bouts of reactivation are normally controlled by the immune
system, but can be fatal in immuno-compromised individuals such as organ
transplant recipients. Here, we reveal that HCMV latency in human CD34(+) HSC
reflects the recruitment on the viral genome of KAP1, a master co-repressor,
together with HP1 and the SETDB1 histone methyltransferase, which results in
transcriptional silencing. During lytic infection, KAP1 is still associated with
the viral genome, but its heterochromatin-inducing activity is suppressed by mTOR
mediated phosphorylation. Correspondingly, HCMV can be forced out of latency by
KAP1 knockdown or pharmacological induction of KAP1 phosphorylation, and this
process can be potentiated by activating NFkB with TNF-alpha. These results
suggest new approaches both to curtail CMV infection and to purge the virus from
organ transplants.
PMID- 25846576
TI - Protection against Helicobacter pylori infection in BALB/c mice by oral
administration of multi-epitope vaccine of CTB-UreI-UreB.
AB - Chronic gastric infection by the Gram-negative bacterium Helicobacter pylori (H.
pylori) is strongly associated with gastritis, gastric ulcer and the development
of distal gastric carcinoma and gastric mucosal lymphoma in humans. Antibiotic
treatment of H. pylori is becoming less effective because of increasing
antibiotic resistance; other treatment approaches such as specifically targeted
methods, etc. to destroy this organism would be beneficial. An epitope vaccine is
a promising option for protection against H. pylori infection. In this study, a
multi-epitope vaccine was constructed by linking cholera toxin B subunit (CTB),
two antigenic fragments of H. pylori urease I subunit (UreI20-29, UreI98-107) and
four antigenic fragments of H. pylori urease B subunit (UreB12-23, UreB229-251,
UreB327-400, UreB515-561), resulting in the recombinant CTB-UreI-UreB (BIB). Its
protective effect against H. pylori infection was evaluated in BALB/c mice.
Significant protection against H. pylori challenge was achieved in BALB/c mice
immunized with BIB (15/18, 83.3%), rIB plus rCTB (6/18, 33.3%) and rIB (2/18,
11.1%) separately, while no protective effect was found in the mice immunized
with either adjuvant rCTB alone or PBS. The induction of significant protection
against H. pylori is possibly mediated by specific serum IgA and mucosal sIgA
antibodies, and a mixed Th1/Th2/Th17 cells response. This multi-epitope vaccine
might be a promising vaccine candidate that helps to control H. pylori infection.
PMID- 25846577
TI - Treatment escalation options for patients with type 2 diabetes after failure of
exenatide twice daily or glimepiride added to metformin: results from the
prospective European Exenatide (EUREXA) study.
AB - AIMS: To evaluate third-line thiazolidinedione (TZD) or glimepiride therapy in
patients inadequately controlled on metformin + exenatide twice daily, and third
line exenatide twice daily in patients inadequately controlled on metformin +
glimepiride. METHODS: In this randomized, open-label, multicentre trial, 144
patients with type 2 diabetes inadequately controlled [glycated haemoglobin
(HbA1c) >9% (75 mmol/mol) after 3 months' treatment or >7% (53 mmol/mol) at two
consecutive visits 3 months apart, after 6 months' treatment] on metformin +
exenatide twice daily were re-randomized to add-on TZD or glimepiride, and 166
patients inadequately controlled on metformin + glimepiride received add-on
exenatide twice daily. Changes in HbA1c, body mass index (BMI), lipids,
hypoglycaemia and vital signs were evaluated. RESULTS: The median duration of
triple therapy was ~2 years. In patients inadequately controlled on metformin +
exenatide twice daily, add-on TZD decreased HbA1c levels significantly better
than add-on glimepiride: 130-week difference 0.48% [95% confidence interval (CI)
0.19-0.77] or 5.2 mmol/mol (95% CI 2.1-8.4; p = 0.001), but with significantly
increased BMI and systolic blood pressure. The ratio of documented symptomatic
(blood glucose <=70 mg/dl [3.9 mmol/l]) hypoglycaemia rates for add-on
glimepiride to add-on TZD was 8.48 (p < 0.0001). Add-on exenatide twice daily
after metformin + glimepiride significantly reduced HbA1c levels: mean [standard
deviation (s.d.)] change from baseline -0.35 (0.89)% [-3.8 (9.7) mmol/mol] and
BMI: mean (s.d.) change from baseline -0.82 (1.9) kg/m(2) at 130 weeks, with a
slightly increased rate of documented symptomatic hypoglycaemia from metformin +
glimepiride (ratio 1.49). CONCLUSIONS: TZD, but not glimepiride, was an effective
and well tolerated third-line therapy in patients without glycaemic control after
long-term therapy with metformin + exenatide twice daily. Exenatide twice daily
was an effective and well tolerated third-line therapy in patients inadequately
controlled on metformin + glimepiride.
PMID- 25846578
TI - Synthesis and characterization of nanosilver with antibacterial properties using
Pinus densiflora young cone extract.
AB - This study describes an eco-friendly, rapid method for green synthesis of silver
nanoparticles (Ag NPs) from an aqueous solution of silver nitrate using Pinus
densiflora for. multicaulis Uyeki young cone extract in a single-pot process.
Color changes, ultraviolet-visible spectra (444.5 nm), X-ray diffraction peaks
(2theta=39.68, 46.92, 68.12, and 79.10), and Fourier transform infrared
spectroscopy (FT-IR) confirmed the presence of Ag NPs and phytochemicals.
Transmission electron microscopy showed that the nanoparticles were mostly oval
in shape, with a few triangular-shaped particles. Average particle size was 30-80
nm. Phytochemicals present in the young pine cone extract were likely responsible
for the reduction of Ag(+) ions. The synthesized Ag NPs (40 MUg) had a 7 mm
larger zone of inhibition against the skin pathogen Brevibacterium linens than
commercial Ag NPs, Propionibacterium acnes (14 mm), Bacillus cereus (9 mm) and
Staphylococcus epidermidis (10mm).
PMID- 25846579
TI - Vitamin D and ultraviolet phototherapy in Caucasians.
AB - Ultraviolet B (UVB) radiation increases vitamin D level, but the influence of
different UV sources (broadband and narrowband UVB lamps, solar simulators and
sunbeds) and exposure durations have not been well characterized. In this study
the influence of different UV sources on serum 25-hydroxyvitamin-D3 (25(OH)D3)
levels in humans are reviewed. Serum 25(OH)D levels before and after UV exposure,
and UV doses were extracted from 18 papers published in the past eight years. It
was found that the UV dose-response curve for vitamin D generation in humans, as
measured by the increments of serum 25(OH)D, is not linear with increasing UV
doses and reaches a plateau at about 55 nmol/L after 4-5 weeks. About a half of
this increase is equal to the difference between winter and summer 25(OH)D
levels, and may be reached after 23 SEDs. The increments decrease with increasing
baseline concentration of serum 25(OH)D, and the efficiency of only 0.7 nmol/L
per SED is expected on the average when initial concentrations are higher than 50
60 nmol/L. A whole body exposure to 2 SEDs of UVB radiation 3 times per week is
expected to rise serum 25(OH)D with an initial rate of 3.9 nmol/L per SED,
bringing a winter level of serum 25(OH)D up to a summer level.
PMID- 25846580
TI - Oscillatory signatures of crossmodal congruence effects: An EEG investigation
employing a visuotactile pattern matching paradigm.
AB - Coherent percepts emerge from the accurate combination of inputs from the
different sensory systems. There is an ongoing debate about the
neurophysiological mechanisms of crossmodal interactions in the brain, and it has
been proposed that transient synchronization of neurons might be of central
importance. Oscillatory activity in lower frequency ranges (<30Hz) has been
implicated in mediating long-range communication as typically studied in
multisensory research. In the current study, we recorded high-density
electroencephalograms while human participants were engaged in a visuotactile
pattern matching paradigm and analyzed oscillatory power in the theta- (4-7Hz),
alpha- (8-13Hz) and beta-bands (13-30Hz). Employing the same physical stimuli,
separate tasks of the experiment either required the detection of predefined
targets in visual and tactile modalities or the explicit evaluation of crossmodal
stimulus congruence. Analysis of the behavioral data showed benefits for
congruent visuotactile stimulus combinations. Differences in oscillatory dynamics
related to crossmodal congruence within the two tasks were observed in the beta
band for crossmodal target detection, as well as in the theta-band for congruence
evaluation. Contrasting ongoing activity preceding visuotactile stimulation
between the two tasks revealed differences in the alpha- and beta-bands. Source
reconstruction of between-task differences showed prominent involvement of
premotor cortex, supplementary motor area, somatosensory association cortex and
the supramarginal gyrus. These areas not only exhibited more involvement in the
pre-stimulus interval for target detection compared to congruence evaluation, but
were also crucially involved in post-stimulus differences related to crossmodal
stimulus congruence within the detection task. These results add to the
increasing evidence that low frequency oscillations are functionally relevant for
integration in distributed brain networks, as demonstrated for crossmodal
interactions in visuotactile pattern matching in the current study.
PMID- 25846582
TI - Two alternative approaches to access mixed hydride-amido zinc complexes:
synthetic, structural and solution implications.
AB - Using bis(amide) Zn(HMDS)2 (HMDS = 1,1,1,3,3,3-hexamethyldisilazide) as a
precursor, this study explores the synthesis of N-heterocyclic carbene stabilized
mixed amido-hydride zinc complexes using two alternative hydride sources, namely
dimethylamine borane (DMAB) and phenylsilane PhSiH3. Hydride-rich zinc cluster
Zn4(HMDS)2H6.2IPr () (IPr = 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidene),
which can be envisaged as a co-complex of IPr.ZnH2 and (HMDS)ZnH, is obtained
when DMAB is employed, with the concomitant formation of heteroleptic
bis(amido)borane [HB(NMe2)(HMDS)] and H2 evolution. NMR studies in d8-THF show
that although the bulky carbene IPr does not bind to the zinc bis(amide), its
presence in the reaction media is required in order to stabilise . Reactions
using the slightly less sterically demanding NHC IXy (IXy = 1,3-bis-(2,6
dimethylphenyl)imidazol-2-ylidene) led to the isolation and structural
elucidation of the carbene adduct Zn(HMDS)2.IXy (). Contrastingly, mixtures of
equimolar amounts of PhSiH3 and the zinc bis(amide) (60 degrees C, 3 h, hexane)
afforded monomeric heteroleptic hydride (HMDS)ZnH.IPr (). NMR studies, including
DOSY experiments, revealed that while the integrity of is retained in polar d8
THF solutions, in lower polarity C6D6 it displays a much more complex solution
behaviour, being in equilibrium with the homoleptic species ZnH2.IPr, Zn(HMDS)2
and IPr.
PMID- 25846581
TI - A qualitative exploration of the impact of the economic recession in Spain on
working, living and health conditions: reflections based on immigrant workers'
experiences.
AB - BACKGROUND: This study aimed to analyse how immigrant workers in Spain
experienced changes in their working and employment conditions brought about
Spain's economic recession and the impact of these changes on their living
conditions and health status. METHOD: We conducted a grounded theory study. Data
were obtained through six focus group discussions with immigrant workers (n = 44)
from Colombia, Ecuador and Morocco, and two individual interviews with key
informants from Romania living in Spain, selected by theoretical sample. RESULTS:
Three categories related to the crisis emerged--previous labour experiences,
employment consequences and individual consequences--that show how immigrant
workers in Spain (i) understand the change in employment and working conditions
conditioned by their experiences in the period prior to the crisis, and (ii)
experienced the deterioration in their quality of life and health as consequences
of the worsening of employment and working conditions during times of economic
recession. CONCLUSION: The negative impact of the financial crisis on immigrant
workers may increase their social vulnerability, potentially leading to the
failure of their migratory project and a return to their home countries. Policy
makers should take measures to minimize the negative impact of economic crisis on
the occupational health of migrant workers in order to strengthen social
protection and promote health and well-being.
PMID- 25846583
TI - Postmenopausal hormone therapy-also use of estradiol plus levonorgestrel
intrauterine system is associated with an increased risk of primary fallopian
tube carcinoma.
AB - Data on the possible impact of postmenopausal hormone therapy (HT) on the
incidence of rare primary fallopian tube carcinoma (PFTC) are scarce. Therefore,
we conducted a nationwide case-control study analyzing the association between
the use of different HTs and PFTC. All women aged 50 years or older with an
incident PFTC (n = 360) during 1995-2007 were identified from the Finnish Cancer
Registry. For each case of PFTC, ten age- and place of residence-matched controls
were selected from the Finnish National Population Register, which also provided
information on parity. Data on HT purchases were received from the Prescription
Register, and data on hysterectomies and sterilizations from the National Care
Register. Controls with a salpingectomy before the PFTC diagnosis of the
respective case were excluded. The PFTC risk in relation to different HTs was
estimated with a conditional logistic regression model, adjusted for parity, age
at last delivery, hysterectomy and sterilization. The use for five years or more
of estradiol combined with levonorgestrel-releasing-intrauterine system (odds
ratio 2.84, 95% confidence interval 1.10-7.38) and sequential estradiol-progestin
therapy (EPT; 3.37; 2.23-5.08) were both linked with increases in the risk of
PFTC, while the risk with use of estradiol-only therapy or continuous EPT was not
statistically significantly increased. The OR for the use of tibolone for one
year or more was 1.56 (0.55-4.41). The use of HT is related to an increased risk
of PFTC, particularly when a progestin component is intrauterine or systemic
progestin is given in sequential manner.
PMID- 25846584
TI - Pretreatment with lipopolysaccharide attenuates diethylnitrosamine-caused liver
injury in mice via TLR4-dependent induction of Kupffer cell M2 polarization.
AB - In this study, we found that pretreatment with low dose of lipopolysaccharide
(LPS), also known as lipoglycans and endotoxin, obviously attenuated liver injury
caused by diethylnitrosamine (DEN) in mice. This protective effect was described
by decreased ALT, TNF-alpha, and IL-1beta and increased TGF-beta production.
However, Toll-like receptor 4-deficient (TLR4(-/-)) or macrophages depletion
abolished this protection in mice, which revealed Kupffer cells (KCs) and TLR4 to
be crucial for the prevention of LPS against DEN-induced damage. Further study
revealed that LPS pretreatment induced the KCs to M2 polarization and impaired
the signaling of MAPKs and NF-kappaB that mediated the production of inflammatory
cytokines. Moreover, T regulatory cells (Tregs) were also recruited to the liver,
which may mediate immunosuppression and participate in the prevention of DEN
induced injury. Our results suggested that LPS protected against DEN-induced
hepatitis via induction of M2 Kupffer cells and recruitment of Tregs, which
contributes to liver tolerance in TLR4-dependent mechanism.
PMID- 25846585
TI - Single nucleotide polymorphisms in the FAM167A-BLK gene are associated with
polymyositis/dermatomyositis in the Han Chinese population.
AB - Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases influenced by
genetic background and environmental factors. Recently, FAM167A-BLK gene has been
identified as a potential genetic susceptibility locus for dermatomyositis (DM)
in patients of European and Japanese populations. Our aim here was to investigate
the association between FAM167A-BLK polymorphisms and IIMs risk in Chinese Han.
The FAM167A-BLK single nucleotide polymorphisms (SNPs) rs2736340, rs7812879,
rs13277113, rs2618479, rs2254546 and rs2248932 were analyzed in polymyositis (PM)
patients (n = 310), DM patients (n = 535) and 968 ethnically matched healthy
controls, with the Sequenom MassArray system. Our present study demonstrated that
strong allele association was observed in overall PM/DM and PM patients for
rs2736340 (P c = 6.48 * 10(-3); P c = 0.013, respectively), rs7812879 (P c =
0.017; P c = 0.034, respectively) and rs13277113 (P c = 0.011; P c = 0.047,
respectively). These three SNPs were significantly associated with interstitial
lung disease (ILD) in overall PM/DM patients (all, P c < 0.05). The frequency of
the five haplotypes of the five SNPs (rs2736340, rs7812879, rs13277113, rs2618479
and rs2254546) was also significantly different between overall PM/DM, PM or DM
patients and healthy controls. This was the first study to demonstrate that the
FAM167A-BLK polymorphisms were associated with Chinese PM/DM patients or these
patients with ILD, indicating that PM/DM might share common gene with other
autoimmune diseases.
PMID- 25846586
TI - [Neuropathology of cerebral cortices in neurodegenerative disorders].
AB - Clinical symptoms and signs are important keys to detect cortical lesions of
neurological disorders. Each disease presents with characteristic cortical
lesions and distributions of abnormal inclusions. In the cerebral cortices,
neuronal and glial inclusions consist of abnormally aggregated proteins, such as
tau or TDP-43, which are disease-specific. However, neurological disorders span
across a wide spectrum and individual variations exist in within populations of
the same disease. Therefore, knowledge about disease-specific pathologies may
provide useful guidelines for differential diagnosis of cortical lesions
occurring in neurological diseases.
PMID- 25846587
TI - [What matters more in the white matter: thinking inside of the brain].
AB - The proportion of white matter in the brain has increased during evolution, and
white matter comprises approximately half of the human brain. Its macroscopic as
well as microscopic structures change during development, aging, and disease
progression as well as following physical or mental training. Knowledge about the
structural plasticity of the white matter may alter our cortex-oriented view of
brain functions and expand our strategies for diagnosis and treatment, including
rehabilitation, since the gray and white matter are complementary. Although the
presence of white matter lesions is easy to detect with magnetic resonance
imaging of the brain, their qualitative differentiation requires vast knowledge
about the underlying processes. Examples from multiple ischemic lesions caused by
different disease processes affecting the cerebral arteries are presented for
comparison. It is worth considering "what matters more in the white matter" by
taking into account the basic structures of the brain as well as their
plasticity. Such "thinking inside of the brain" may further expand our
understanding of the brain to improve our clinical interpretations and
treatments.
PMID- 25846588
TI - [Current concepts regarding cortical dementia].
AB - Dementia manifests during the presenile and senile periods in many diseases and
pathological conditions. Alzheimer's disease (AD) and frontotemporal lobar
degeneration (FTLD) are the two main diseases in which cortical dementia is
observed. FTLD includes frontotemporal dementia (FTD), progressive non-fluent
aphasia (PNFA), and semantic dementia (SD). Cortical dementia has also been
described in posterior cortical atrophy (CPA) and primary progressive non-fluent
or logopenic aphasia (PNFLA). This article describes and discusses historical
changes in the disease concept; diagnostic characteristics, including pathology
and imaging analysis; clinical symptoms based on local cognitive function in the
cerebral cortex; and other recent topics on dementia.
PMID- 25846589
TI - [Subcortical ischemic vascular dementia: lesson from hereditary cerebral small
vessel disease].
AB - Subcortical ischemic vascular dementia (SIVD) is a main subgroup of vascular
dementia related to cerebral small vessel disease. Risk factors for SIVD include
hypertension, ageing, and diabetes mellitus, but the specific contribution of
each factor to the development of cerebral small vessel disease remains obscure.
This is mainly because SIVD in the elderly might be affected by many factors
related to the ageing process. Hereditary cerebral small vessel diseases,
including cerebral autosomal-dominant or autosomal recessive arteriopathy with
subcortical infarcts and leukoencephalopathy (CADASIL or CARASIL) and cerebral
amyloid angiopathy, are affected by different pathomechanisms, but these diseases
indicate a clear a role of the cerebral small vessel on subcortical dementia.
CADASIL is caused by a cysteine residue-related mutation in the EGF-like repeat
on the extracellular domain of Notch3. Pathological examination of a CADASIL
brain indicated abnormal accumulation of the extracellular domain of Notch3 with
extracellular matrix proteins, including tissue inhibitor of metalloproteinase 3
and vitronectin, around vascular smooth muscle cells. CARASIL is caused by a
mutation in HTAR1, a serine protease that regulates transforming growth factor
(TGF)-beta signaling. The mutation in HTAR1 related to CARASIL fails to repress
TGF-beta signaling and induces the accumulation of extracellular matrix,
including the extra domain-A region of fibronectin and versican. The individual
and common pathomechanisms of hereditary cerebral small vessel disease are
discussed in this review.
PMID- 25846590
TI - [Differential diagnosis of dementia with lewy bodies].
AB - Kosaka and colleagues first reported dementia with Lewy bodies (DLB) in 1976.
They have also established the concept of DLB. It is important to differentiate
DLB from other dementia, especially Alzheimer disease (AD), because the medical
treatment, management, and prognosis of DLB and AD are different. We have used
several clinical features and imaging tools to differentiate between DLB and AD.
With regard to clinical features, patients with DLB have relatively mild memory
disturbances and fluctuating cognition. However, compared to patients with AD
they have more severe disturbances of attention and executive, visuospatial
functions, visual hallucination, depression, autonomic symptoms. In addition,
they show the presence of REM sleep behavior disorder and idiopathic
parkinsonism. On performing imaging analysis, patients with DLB showed milder
atrophy in the medial temporal lobe on brain MRI, reduced occipital activity on
SPECT or PET, reduced MIBG uptake on MIBG cardiac scintigraphy, and low dopamine
transporter activity in the basal ganglia on SPECT or PET.
PMID- 25846591
TI - [White Matter Lesion and Alzheimer's Disease: The Association between Small
Vessel Disease and Neuropsychiatric Symptoms in Alzheimer's Disease].
AB - Cerebral small vessel disease (SVD), including subcortical lacunar infarcts
(lacunes) and white matter hyperintensities (WMH), is commonly observed on MRI of
elderly individuals with and without dementia. SVD is frequently observed in
patients with Alzheimer's disease (AD). However, the association between SVD and
clinical symptoms exhibited by patients with AD remains unclear. Our recent
studies suggest that cerebral SVD observed on CT/MRI of patients with AD is
associated with delusions and delirium as well as depression. Mechanisms
underlying these psychiatric symptoms in patients with AD remain unclear.
PMID- 25846592
TI - [Understanding the neuropsychological symptoms associated with cortical
dysfunction].
AB - Damage to association cortices can result in a variety of cognitive and
behavioral symptoms. Superficially, the relationship between lesion sites and the
corresponding symptoms seems constant. However, some degree of dissociation of
symptoms among patients with different etiologies appears to be the rule rather
than the exception, even when the lesion locations appear similar in neuroimaging
studies. Examinations of patients with primary progressive aphasia (PPA) have
challenged the classic language model that is based on observations mainly made
in patients with cerebrovascular diseases. The neuropsychological findings of
patients with semantic variant PPA and neuroimaging evidence in healthy subjects
converge to indicate that the anterior temporal lobe is an important component of
language and semantic networks. Recent findings, however, have demonstrated that
atrophy and dysfunction in patients with semantic variant PPA involve a number of
regions in addition to the anterior temporal lobe. This indicated that
specifically linking language deficits to the anterior temporal lobe is
difficult. An understanding the pathophysiological processes is require to
comprehend the symptoms of cortical dysfunction, especially in the association
cortices.
PMID- 25846593
TI - [Investigating the symptoms of white matter disorders].
AB - In this presentation, I will examine the intricate systemic connections in the
white matter and the disturbances that occur due to diseases. In particular, I
will discuss Marchiafava-Bignami disease, leukodystrophy with neuroaxonal
spheroids, and myotonic dystrophy. Investigation of all three diseases reveals
the crosstalk essential for the healthy brain and the resulting dysfunctions that
follow lesions of different etiologies.
PMID- 25846594
TI - [Investigation of the Cerebral Cortex Using Magnetoencephalography(MEG)].
AB - Cortical neurons are excited by signals from the thalamus that are conducted via
thalamocortical fibers. As the cortex receives these signals, electric currents
are conducted through the apical dendrites of pyramidal cells in the cerebral
cortex. These electric currents generate magnetic fields. These electric and
magnetic currents can be recorded by electroencephalography (EEG) and
magnetoencephalography (MEG), respectively. The spatial resolution of MEG is
higher than that of EEG because magnetic fields, unlike electric fields, are not
affected by current conductivity. MEG also has several advantages over functional
magnetic resonance imaging (fMRI). It (1) is completely non-invasive; (2)
measures neuronal activity rather than blood flow or metabolic changes; (3) has a
higher temporal resolution than fMRI on the order of milliseconds; (4) enables
the measurement of stimulus-evoked and event-related responses; (5) enables the
analysis of frequency (i.e., brain rhythm) response, which means that
physiological changes can be analyzed spatiotemporally; and (6) enables the
detailed analysis of results from an individual subject, which eliminates the
need to average results over several subjects. This latter advantage of MEG
therefore enables the analysis of inter-individual differences.
PMID- 25846595
TI - [Cerebral white matter lesions: differential diagnosis on magnetic resonance
imaging].
AB - It is often difficult to make a differential diagnosis of cerebral white-matter
lesions on magnetic resonance images (MRI), because imaging findings are non
specific. However, it is possible to make a correct diagnosis of some kinds of
cerebral white-matter lesions upon a detailed analysis of MRI. In analyzing MRI
of cerebral white matter lesions, the localization and shape of white-matter
lesions are important factors to make a differential diagnosis. Other images such
as diffusion-weighted or T2-star weighted images are sometimes also useful for
making such a diagnosis. In this manuscript, I describe how to read MRI of
cerebral white-matter lesions, and present some educational cases.
PMID- 25846596
TI - [White matter fiber tractography and quantitative analysis of diffusion tensor
imaging].
AB - Magnetic resonance diffusion tensor imaging (DTI) is a noninvasive technique that
can identify and quantify white matter tracts by evaluating the diffusion of
water in biological tissues. While association fibers are bundles of axons within
the brain that unite different parts of the same cerebral hemisphere, projection
fibers are bundles of axons that unite the cortex with lower parts of the brain
and the spinal cord. The commissural fibers are axon bundles that connect the two
hemispheres of the brain. Quantitative analysis of DTI can be roughly classified
into three types: region of interest analysis, tract-specific analysis, and fully
automated hypothesis free whole brain analysis.
PMID- 25846597
TI - [Volumetry of cerebral gray and white matter using VSRAD(r)].
AB - Voxel-based morphometry (VBM) using structural brain MRI has been widely used for
the early and differential diagnosis and evaluation of disease progression in
neuropsychiatric diseases. VBM of MRI data comprises segmentation into gray
matter, white matter, and cerebrospinal fluid partitions; anatomical
standardization of all the images to the same stereotactic space using linear
affine transformation and further non-linear warping and smoothing; and finally
performing statistical analysis. Stand-alone VBM software using SPM8 plus DARTEL
running on Windows (Voxel-based Specific Regional analysis system for Alzheimer's
disease, VSRAD(r)) has been developed as an adjunct to the clinical
assessment. This software provides a Z-score map as a result of the comparison of
the patient's MRI with a normal database.
PMID- 25846598
TI - [Cortical gray matter lesions in multiple sclerosis].
AB - Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the two main
autoimmune and inflammatory diseases of the central nervous system. MS is
considered an 'oligodendrocytopathy' with undefined autoantibodies, whereas NMO
is considered an 'astrocytopathy' with aquaporin-4 antibodies. Both have long
been considered autoimmune diseases that primarily affect the white matter (WM).
However, recent interest in gray matter (GM) pathology is emerging. Pathological
evaluations reveal that substantial cortical demyelination is prominent at all
stages or courses of MS. In addition, the neurodegeneration in MS is present not
only in GM demyelination but also in normal-appearing GM. NMO involves cortical
neurodegeneration and unique dynamics of astrocytes; however, no cortical
demyelination is seen. Thus, MS and NMO are distinct diseases with unique
pathological features in the brain WM and GM. Although the cause of GM and WM
lesions in MS and NMO has not been fully determined, improved knowledge about the
pathomechanisms in affected brains is desired. This would result in a more
targeted pharmacotherapeutic approach to these diseases.
PMID- 25846599
TI - [Brain function and white matter].
AB - Accumulated evidence shows that neural information processing takes place in
superficial layers of the brain called the gray matter. Synapses, which connect
different neurons reside in the gray matter and are considered the major
components of information processing and plasticity. On the other hand,
myelinated axons lie beneath the gray matter. These bundles of cables connect
neurons in the different brain regions to form functional neural circuits.
Myelinated axons were of little of interest to neuroscientists and have long been
ignored in the formation of functional neuronal circuits. Recent evidence shows
that myelin formed by oligodendrocytes shows plastic changes depending on
neuronal activity. In this issue, we discuss the plastic changes of myelin and
its functional role in learning and training.
PMID- 25846600
TI - [Criteria for the diagnosis of corticobasal degeneration].
AB - Corticobasal degeneration (CBD) is a distinct neurodegenerative disorder
characterized by widespread neuronal and glial accumulation of abnormally
phosphorylated tau protein. Patients with CBD often present with corticobasal
syndrome (CBS) showing impairment of the motor system, cognition, or both.
Several studies demonstrate that they may also present with progressive
supranuclear palsy syndrome (PSPS), aphasia, Alzheimer disease-like dementia, or
behavioral changes, suggesting that CBS is merely one of the presenting
phenotypes of CBD. Accurate diagnosis is important for future clinical trials
using drugs aimed at modifying the underlying tau pathology. Although previous
CBD diagnostic criteria reflected only CBS, Armstrong et al. proposed new
diagnostic criteria for CBD in 2013 (Armstrong's criteria). The new criteria
include 4 CBD phenotypes, including CBS, frontal behavioral-spatial syndrome
(FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and
PSPS. These phenotypes were combined to create 2 sets of criteria: specific
clinical research criteria for probable CBD (cr-CBD) and broader criteria for
possible CBD that are more inclusive but have a higher probability of detecting
other tau-based pathologies (p-CBD). However, two recent studies revealed that
the sensitivity and specificity of these criteria were insufficient. Further
refinement of the criteria is needed via biomarker research with prospective
study designs. (Received August 19, 2014; Accepted December 26, 2014: Published
April 1, 2015).
PMID- 25846601
TI - [Clinical and histological characteristics of ictal onset zone in cases of
intractable epilepsy associated with dysembryoplastic neuroepithelial tumor].
AB - Although the epileptogenic location of dysembryoplastic neuroepithelial tumors
(DNTs) is controversial, it has recently been thought to be located within
cortical dysplasia (CD) due to its frequent association with CD. Among the 84
resection surgeries for intractable epilepsy performed in our institution between
January 2003 and April 2010, three patients had epileptogenic DNTs. In two cases,
chronic subdural electrocorticography (ECoG) was performed, and the ictal onset
zone was revealed to be in the cortex around the DNT. The ictal onset zone was
resected along with the DNT, and good seizure outcome was achieved. Although
histological examination of the ictal onset zone revealed mild gliosis,
coexistence of CD was not noted. In the third case, the DNT was located in the
left lateral temporal lobe and the intraoperative ECoG revealed frequent
paroxysmal activity in the medial temporal lobe. Resection of the lateral
temporal lobe involving the tumor did not result in good seizure control. The
optimal surgical treatment of DNT is controversial. Some authors consider
lesionectomy to be sufficient for good seizure control, whereas others advocate
that additional resection of the epileptogenic zone beside the tumor improves
outcome. Because the epileptogenic location of DNT varies among cases, it is
important to identify its location by preoperative multimodal examinations,
including chronic subdural ECoG recordings.
PMID- 25846603
TI - Editorial: Diet and children's behaviour problems--disentangling urban myth from
clinical reality.
PMID- 25846602
TI - Pharmacists' knowledge about use of topical corticosteroids in atopic dermatitis:
Pre and post continuing professional development education.
AB - BACKGROUND/OBJECTIVES: Topical corticosteroids (TCS) are the standard of care in
paediatric atopic dermatitis (pAD). Parents commonly cite TCS phobia as a major
impediment to treatment adherence. Misinformation on TCS side-effects can impact
on perceptions of TCS safety. We aimed to assess pharmacists' beliefs and
information on the safety of TCS in pAD treatment and determine whether their
beliefs could be modified. METHODS: Australian pharmacists attending a continuing
professional development conference were assessed before and after an evidence
based lecture on the use of TCS in pAD. Responses were recorded in real time on
electronic keypads. RESULTS: The mean response rate was 86% of the 292 surveyed.
Of responders, 64% recognised that treatment non-adherence was a major reason for
treatment failure in pAD. The post-education session assessment demonstrated a
major attitude shift compared to the pre-education assessment. After education,
pharmacists would instruct parents/patients to apply TCS until the eczema is
clear (27 vs 92% pre and post-education, P < 0.0001). The proportion that would
instruct patients to use TCS sparingly dropped from 54 to 8% (P < 0.0001). The
belief that cutaneous atrophy was the commonest side-effect dropped from 46 to 7%
(P < 0.0001). The belief that side-effects from TCS would occur, even if used
appropriately, dropped from 56 to 11% post-education (P < 0.0001). CONCLUSIONS:
The significant knowledge gaps about the use and safety of TCS in pAD in
Australian pharmacists and their advice to patients potentially contributes to
poor treatment concordance. These attitudes appear modifiable through targeted,
evidence-based education delivered by a dermatologist.
PMID- 25846604
TI - Mesenchymal stem cell application in children with subacute sclerosing
panencephalitis.
AB - Subacute sclerosing panencephalitis (SSPE) is a serious, often fatal disease that
responds poorly to current treatment modalities. Recently, the ability of
mesenchymal stem cells (MSCs) to produce neurotrophic factors and inflammatory
molecules has placed them among potential treatment agents for neurological
conditions. We report the results of four patients treated with MSC for SSPE. The
patients were followed up clinically, and by periodical laboratory evaluations,
magnetic resonance imaging (MRI), and electroencephalography. One patient
deteriorated to stage III of the disease, two patients remained in the same
stage, and one died from disease progression and respiratory problems.
Neurological findings and electroencephalography scores were consistent with the
clinical course of the patient whereas MRI showed new inflammatory lesions in two
patients. This is the first report of the application of MSC in SSPE. No benefit
is demonstrated.
PMID- 25846605
TI - Gene expression of cultured human chondrocytes as a model for assessing
neutralization efficacy of soluble TNFalpha by TNFalpha antagonists.
AB - Tumor necrosis factor-alpha (TNFalpha) antagonists are efficacious in the
treatment of various immune-mediated inflammatory diseases. Because of rapidly
growing demand for developing new or biosimilar versions of these biologicals,
the need to create in vitro testing models that best represent physiological
conditions is increasing. Primary human chondrocytes were used for potency
evaluation and comparison between the molecular effects of anti-TNFalpha
biologicals. Infliximab and etanercept were chosen to assess the suitability of
chondrocyte cell culture for determination of anti-TNFalpha neutralization
efficacy employing quantitative reverse transcription-polymerase chain reaction
(qRT-PCR) technology. Use of both anti-TNFalpha biologics resulted in decrease of
TNFalpha-stimulated expression of various matrix metalloproteinases, interleukins
and other inflammation-related genes in our cell model. Significant differences
in inhibition efficacy of etanercept and infliximab were observed, which were
confirmed also on protein level. To evaluate the potency of anti-TNFalpha
biologicals, a selection of TNFalpha-responsive target genes was made from the
gene array data. The selected genes were employed in development of statistical
model, which enables comparability of anti-TNFalpha biologicals. The presented
analytical approach is suitable for assessment of the neutralization efficacy of
various anti-TNFalpha biologicals. As such, it can be used for additional
comprehensive characterization and comparability of TNF antagonists in
preclinical drug testing.
PMID- 25846606
TI - Residential radon and birth defects: A population-based assessment.
AB - BACKGROUND: Associations have been reported between maternal radiation exposure
and birth defects. No such studies were found on radon. Our objective was to
determine if there is an association between living in areas with higher radon
levels and birth defects. METHODS: The Texas Birth Defects Registry provided data
on all birth defects from 1999 to 2009 from the entire state. Mean radon levels
by geologic region came from the Texas Indoor Radon Survey. The association
between radon and birth defects was estimated using multilevel mixed effect
Poisson regression. RESULTS: Birth defects overall were not associated with
residential radon levels. Of the 100 other birth defect groups with at least 500
cases, 14 were significantly elevated in areas with high mean radon level in
crude analyses, and 9 after adjustment for confounders. Cleft lip with/without
cleft palate had an adjusted prevalence ratio of 1.16 per 1 picoCurie/liter
(pCi/L) increase in exposure to region mean radon, 95% confidence interval, 1.08
1.26. Cystic hygroma / lymphangioma had an adjusted prevalence ratio of 1.22 per
1 pCi/L increase, 95% confidence interval, 1.02-1.46. Other associations were
suggested but not as consistent: three skeletal defects, Down syndrome, other
specified anomalies of the brain, and other specified anomalies of the bladder
and urethra. CONCLUSION: In the first study of residential radon and birth
defects, we found associations with cleft lip w/wo cleft palate and cystic
hygroma / lymphangioma. Other associations were suggested. The ecological nature
of this study and multiple comparisons suggest that our results be interpreted
with caution.
PMID- 25846607
TI - Inhibition of autophagy using 3-methyladenine increases cisplatin-induced
apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells.
AB - Cisplatin is one of the most widely used chemotherapeutic drugs; however, the
side effects and drug resistance limit its usage. Previous findings have
demonstrated that cisplatin kills tumor cells through endoplasmic reticulum (ER)
stress, which provides a novel method to minimize cisplatin toxicity and
circumvent cisplatin resistance. ER stress induces cell autophagy, cell apoptosis
and the complicated regulatory network between them. The role of autophagy in
cisplatin chemotherapy remains to be elucidated. 3-Methyladenine (3-MA) is
normally used as an inhibitor of autophagy. The present study reveals a
significant role of the inhibition of autophagy by treatment with 3-MA and
cisplatin in combination in U251 human glioma cells. It was demonstrated that
cisplatin induced the ER stress associated with apoptosis and autophagy in U251
cells. Inhibition of autophagy by 3-MA increased the expression levels of protein
disulfide isomerase, ubiquitinated proteins, glucose regulated protein 78 and
CCAAT-enhancer-binding protein homologous protein, and induced the activation of
caspase-4 and caspase-3. Treatment with 3-MA combined with cisplatin increased
cisplatin-induced apoptosis by increasing ER stress. Therefore, the inhibition of
autophagy has the potential to improve cisplatin chemotherapy.
PMID- 25846609
TI - Mechanistic studies of malonic acid-mediated in situ acylation.
AB - We have previously introduced an easy to perform, cost-effective and highly
efficient acetylation technique for solid phase synthesis (SPPS). Malonic acid is
used as a precursor and the reaction proceeds via a reactive ketene that
acetylates the target amine. Here we present a detailed mechanistic study of the
malonic acid-mediated acylation. The influence of reaction conditions, peptide
sequence and reagents was systematically studied. Our results show that the
methodology can be successfully applied to different types of peptides and
nonpeptidic molecules irrespective of their structure, sequence, or conformation.
Using alkyl, phenyl, and benzyl malonic acid, we synthesized various acyl
peptides with almost quantitative yields. The ketenes obtained from the different
malonic acid derived precursors were characterized by in situ (1) H-NMR. The
reaction proceeded in short reaction times and resulted in excellent yields when
using uronium-based coupling agents, DIPEA as a base, DMF/DMSO/NMP as solvents,
Rink amide/Wang/Merrifield resins, temperature of 20 degrees C, pH 8-12 and 5 min
preactivation at inert atmosphere. The reaction was unaffected by Lewis acids,
transition metal ions, surfactants, or salt. DFT studies support the kinetically
favorable concerted mechanism for CO2 and ketene formation that leads to the
thermodynamically stable acylated products. We conclude that the malonic acid
mediated acylation is a general method applicable to various target molecules.
PMID- 25846610
TI - Enhanced ultrasonography using a nano/microbubble contrast agent for islet
transplantation.
AB - Recent basic and clinical studies have assessed the use of highly sensitive
imaging modalities for visualizing transplanted islets. We investigated the
utility of enhanced ultrasonography, combined with fluorescent acoustic liposome
nano/microbubbles (FALs), for evaluating angiogenesis and the endocrine function
of transplanted islets. BALB/c mice were classified into three groups: Diabetic
mice that underwent syngeneic islet transplantation into the subrenal capsule and
achieved normoglycemia (Tx group); those that failed to achieve normoglycemia (Tx
DM group); and those not receiving any treatment (DM group). Mice were examined
by FAL-enhanced high frequency ultrasonography. The echogenicity of the islets
increased rapidly within the first minute after injection of FALs and remained at
a higher level in the Tx group, while small increases were observed in the other
two groups. In histological assessments, fluorescently stained erythrocytes could
be seen in and around the transplanted islets, indicating that the transplanted
islets were enhanced by infusion of FALs via vessel networks between the
engrafted islets and tissue. Furthermore, the echogenicity correlated
significantly with endocrine parameters, including blood glucose (BG), serum
insulin, and the BG change in the glucose tolerance test. In conclusion, the
echogenicity of the islets under FAS-enhanced ultrasonosonography correlated with
the endocrine status of transplanted islets.
PMID- 25846608
TI - Alstrom Syndrome: Mutation Spectrum of ALMS1.
AB - Alstrom Syndrome (ALMS), a recessive, monogenic ciliopathy caused by mutations in
ALMS1, is typically characterized by multisystem involvement including early cone
rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2
diabetes mellitus, cardiomyopathy, fibrosis, and multiple organ failure. The
precise function of ALMS1 remains elusive, but roles in endosomal and ciliary
transport and cell cycle regulation have been shown. The aim of our study was to
further define the spectrum of ALMS1 mutations in patients with clinical features
of ALMS. Mutational analysis in a world-wide cohort of 204 families identified
109 novel mutations, extending the number of known ALMS1 mutations to 239 and
highlighting the allelic heterogeneity of this disorder. This study represents
the most comprehensive mutation analysis in patients with ALMS, identifying the
largest number of novel mutations in a single study worldwide. Here, we also
provide an overview of all ALMS1 mutations identified to date.
PMID- 25846611
TI - Emerging concepts of pain therapy based on neuronal mechanisms.
AB - Current pain treatment is successful in many patients, but nevertheless numerous
problems have to be solved because still about 20% of the people in the
population suffer from chronic pain. A major aim of pain research is, therefore,
to clarify the neuronal mechanisms which are involved in the generation and
maintenance of different pain states and to identify the mechanisms which can be
targeted for pain treatment. This volume on pain control addresses neuronal pain
mechanisms at the peripheral, spinal, and supraspinal level which are thought to
significantly contribute to pain and which may be the basis for the development
of new treatment principles. This introductory chapter addresses the types of
pain which are currently defined based on the etiopathologic considerations,
namely physiologic nociceptive pain, pathophysiologic nociceptive pain, and
neuropathic pain. It briefly describes the structures and neurons of the
nociceptive system, and it addresses molecular mechanisms of nociception which
may become targets for pharmaceutical intervention. It will provide a frame for
the chapters which address a number of important topics. Such topics are the
concept of hyperalgesic priming, the role of voltage-gated sodium channels and
nerve growth factor (NGF) in different inflammatory and neuropathic pain states,
the hyperalgesic effects of NGF in different tissues, the contribution of
proteinase-activated receptors (PARs) to the development of pain in several
chronic pain conditions, the role of spinal NO and of glial cell activation in
the generation and maintenance of inflammatory and neuropathic pain, the
potential role of spinal inhibitory interneurons, the endogenous endocannabinoid
system, and the importance of nonneuronal immune mechanisms in opioid signaling
in the control of pain, the influence of spinal mechanisms on the expression of
peripheral inflammation, the role of the amygdala and their connections to the
medial prefrontal cortex in pain states, the experimental methods to test central
sensitization of the nociceptive system in humans, and differences and
similarities of the neuronal systems of pain and itch. Finally it will be
discussed that both the concentration on single key molecules of nociception and
the interference with disease-related mediators may provide novel approaches of
pain treatment.
PMID- 25846613
TI - Sodium channels and pain.
AB - Human and mouse genetic studies have led to significant advances in our
understanding of the role of voltage-gated sodium channels in pain pathways. In
this chapter, we focus on Nav1.7, Nav1.8, Nav1.9 and Nav1.3 and describe the
insights gained from the detailed analyses of global and conditional transgenic
Nav knockout mice in terms of pain behaviour. The spectrum of human disorders
caused by mutations in these channels is also outlined, concluding with a summary
of recent progress in the development of selective Nav1.7 inhibitors for the
treatment of pain.
PMID- 25846614
TI - Role of nerve growth factor in pain.
AB - Nerve growth factor (NGF) was first identified as a substance that is essential
for the development of nociceptive primary neurons and later found to have a role
in inflammatory hyperalgesia in adults. Involvement of NGF in conditions with no
apparent inflammatory signs has also been demonstrated. In this review we look at
the hyperalgesic effects of exogenously injected NGF into different tissues, both
human and animal, with special emphasis on the time course of these effects. The
roles of NGF in inflammatory and neuropathic conditions as well as cancer pain
are then reviewed. The role of NGF in delayed onset muscle soreness is described
in more detail than its other roles based on the authors' recent observations.
Acute effects are considered to be peripherally mediated, and accordingly,
sensitization of nociceptors by NGF to heat and mechanical stimulation has been
reported. Changes in the conductive properties of axons have also been reported.
The intracellular mechanisms so far proposed for heat sensitization are direct
phosphorylation and membrane trafficking of TRPV1 by TrkA. Little investigation
has been done on the mechanism of mechanical sensitization, and it is still
unclear whether mechanisms similar to those for heat sensitization work in
mechanical sensitization. Long-lasting sensitizing effects are mediated both by
changed expression of neuropeptides and ion channels (Na channels, ASIC, TRPV1)
in primary afferents and by spinal NMDA receptors. Therapeutic perspectives are
briefly discussed at the end of the chapter.
PMID- 25846612
TI - The pharmacology of nociceptor priming.
AB - Nociceptors and neurons in the central nervous system (CNS) that receive
nociceptive input show remarkable plasticity in response to injury. This
plasticity is thought to underlie the development of chronic pain states. Hence,
further understanding of the molecular mechanisms driving and maintaining this
plasticity has the potential to lead to novel therapeutic approaches for the
treatment of chronic pain states. An important concept in pain plasticity is the
presence and persistence of "hyperalgesic priming." This priming arises from an
initial injury and results in a remarkable susceptibility to normally
subthreshold noxious inputs causing a prolonged pain state in primed animals.
Here we describe our current understanding of how this priming is manifested
through changes in signaling in the primary nociceptor as well as through memory
like alterations at CNS synapses. Moreover, we discuss how commonly utilized
analgesics, such as opioids, enhance priming therefore potentially contributing
to the development of persistent pain states. Finally we highlight where these
priming models draw parallels to common human chronic pain conditions.
Collectively, these advances in our understanding of pain plasticity reveal a
variety of targets for therapeutic intervention with the potential to reverse
rather than palliate chronic pain states.
PMID- 25846615
TI - Central sensitization in humans: assessment and pharmacology.
AB - It is evident that chronic pain can modify the excitability of central nervous
system which imposes a specific challenge for the management and for the
development of new analgesics. The central manifestations can be difficult to
quantify using standard clinical examination procedures, but quantitative sensory
testing (QST) may help to quantify the degree and extend of the central
reorganization and effect of pharmacological interventions. Furthermore, QST may
help in optimizing the development programs for new drugs.Specific translational
mechanistic QST tools have been developed to quantify different aspects of
central sensitization in pain patients such as threshold ratios, provoked
hyperalgesia/allodynia, temporal summation (wind-up like pain), after sensation,
spatial summation, reflex receptive fields, descending pain modulation, offset
analgesia, and referred pain areas. As most of the drug development programs in
the area of pain management have not been very successful, the pharmaceutical
industry has started to utilize the complementary knowledge obtained from QST
profiling. Linking patients QST profile with drug efficacy profile may provide
the fundamentals for developing individualized, targeted pain management programs
in the future. Linking QST-assessed pain mechanisms with treatment outcome
provides new valuable information in drug development and for optimizing the
management regimes for chronic pain.
PMID- 25846616
TI - Nitric oxide-mediated pain processing in the spinal cord.
AB - A large body of evidence indicates that nitric oxide (NO) plays an important role
in the processing of persistent inflammatory and neuropathic pain in the spinal
cord. Several animal studies revealed that inhibition or knockout of NO synthesis
ameliorates persistent pain. However, spinal delivery of NO donors caused dual
pronociceptive and antinociceptive effects, pointing to multiple downstream
signaling mechanisms of NO. This review summarizes the localization and function
of NO-dependent signaling mechanisms in the spinal cord, taking account of the
recent progress made in this field.
PMID- 25846617
TI - The role of the endocannabinoid system in pain.
AB - Preparations of the Cannabis sativa plant have been used to analgesic effect for
millenia, but only in recent decades has the endogenous system responsible for
these effects been described. The endocannabinoid (EC) system is now known to be
one of the key endogenous systems regulating pain sensation, with modulatory
actions at all stages of pain processing pathways. The EC system is composed of
two main cannabinoid receptors (CB1 and CB2) and two main classes of endogenous
ligands or endocannabinoids (ECs). The receptors have distinct expression
profiles, with CB1 receptors found at presynaptic sites throughout the peripheral
and central nervous systems (PNS and CNS, respectively), whilst CB2 receptor is
found principally (but not exclusively) on immune cells. The endocannabinoid
ligands are lipid neurotransmitters belonging to either the N-acyl ethanolamine
(NAEs) class, e.g. anandamide (AEA), or the monoacylglycerol class, e.g. 2
arachidonoyl glycerol (2-AG). Both classes are short-acting transmitter
substances, being synthesised on demand and with signalling rapidly terminated by
specific enzymes. ECs acting at CB1 negatively regulate neurotransmission
throughout the nervous system, whilst those acting at CB2 regulate the activity
of CNS immune cells. Signalling through both of these receptor subtypes has a
role in normal nociceptive processing and also in the development resolution of
acute pain states. In this chapter, we describe the general features of the EC
system as related to pain and nociception and discuss the wealth of preclinical
and clinical data involving targeting the EC system with focus on two areas of
particular promise: modulation of 2-AG signalling via specific enzyme inhibitors
and the role of spinal CB2 in chronic pain states.
PMID- 25846618
TI - The role of glia in the spinal cord in neuropathic and inflammatory pain.
AB - Chronic pain, both inflammatory and neuropathic, is a debilitating condition in
which the pain experience persists after the painful stimulus has resolved. The
efficacy of current treatment strategies using opioids, NSAIDS and
anticonvulsants is limited by the extensive side effects observed in patients,
underlining the necessity for novel therapeutic targets. Preclinical models of
chronic pain have recently provided evidence for a critical role played by glial
cells in the mechanisms underlying the chronicity of pain, both at the site of
damage in the periphery and in the dorsal horn of the spinal cord. Here microglia
and astrocytes respond to the increased input from the periphery and change
morphology, increase in number and release pro-nociceptive mediators such as ATP,
cytokines and chemokines. These gliotransmitters can sensitise neurons by
activation of their cognate receptors thereby contributing to central
sensitization which is fundamental for the generation of allodynia, hyperalgesia
and spontaneous pain.
PMID- 25846619
TI - Plasticity of inhibition in the spinal cord.
AB - Inhibitory interneurons, which use GABA and/or glycine as their principal
transmitter, have numerous roles in regulating the transmission of sensory
information through the spinal dorsal horn. These roles are likely to be
performed by different populations of interneurons, each with specific locations
in the synaptic circuitry of the region. Peripheral nerve injury frequently leads
to neuropathic pain, and it is thought that loss of function of inhibitory
interneurons in the dorsal horn contributes to this condition. Several mechanisms
have been proposed for this disinhibition, including death of inhibitory
interneurons, decreased transmitter release, diminished activity of these cells
and reduced effectiveness of GABA and glycine as inhibitory transmitters.
However, despite numerous studies on this important topic, it is still not clear
which (if any) of these mechanisms contributes to neuropathic pain after nerve
injury.
PMID- 25846620
TI - Modulation of peripheral inflammation by the spinal cord.
AB - The central nervous system, and the spinal cord in particular, is involved in
multiple mechanisms that influence peripheral inflammation. Both pro- and anti
inflammatory feedback loops can involve just the peripheral nerves and spinal
cord or can also include more complex, supraspinal structures such as the vagal
nuclei and the hypothalamic-pituitary axis. Analysis is complicated by the fact
that inflammation encompasses a constellation of end points from simple edema to
changes in immune cell infiltration and pathology. Whether or not any of these
individual elements is altered by any potential mechanism is determined by a
complex algorithm including, but not limited to, chronicity of the inflammation,
tissue type, instigating stimulus, and state/tone of the immune system.
Accordingly, the pharmacology and anatomical substrate of spinal cord modulation
of peripheral inflammation are discussed with regard to peripheral tissue type,
inflammatory insult (initiating stimulus), and duration of the inflammation.
PMID- 25846621
TI - The relationship between opioids and immune signalling in the spinal cord.
AB - Opioids are considered the gold standard for the treatment of moderate to severe
pain. However, heterogeneity in analgesic efficacy, poor potency and side effects
are associated with opioid use, resulting in dose limitations and suboptimal pain
management. Traditionally thought to exhibit their analgesic actions via the
activation of the neuronal G-protein-coupled opioid receptors, it is now widely
accepted that neuronal activity of opioids cannot fully explain the initiation
and maintenance of opioid tolerance, hyperalgesia and allodynia. In this review
we will highlight the evidence supporting the role of non-neuronal mechanisms in
opioid signalling, paying particular attention to the relationship of opioids and
immune signalling.
PMID- 25846622
TI - The role of proteases in pain.
AB - Proteinase-activated receptors (PARs) are a family of G protein-coupled receptor
that are activated by extracellular cleavage of the receptor in the N-terminal
domain. This slicing of the receptor exposes a tethered ligand which binds to a
specific docking point on the receptor surface to initiate intracellular
signalling. PARs are expressed by numerous tissues in the body, and they are
involved in various physiological and pathological processes such as food
digestion, tissue remodelling and blood coagulation. This chapter will summarise
how serine proteinases activate PARs leading to the development of pain in
several chronic pain conditions. The potential of PARs as a drug target for pain
relief is also discussed.
PMID- 25846624
TI - Itch and pain differences and commonalities.
AB - Pain and itch are generally regarded antagonistic as painful stimuli such as
scratching suppresses itch. Moreover, inhibition of pain processing by opioids
generates itch further supporting their opposing role. Separate specific pathways
for itch and pain processing have been uncovered, and several molecular markers
have been established in mice that identify neurons involved in the processing of
histaminergic and non-histaminergic itch on primary afferent and spinal level.
These results are in agreement with the specificity theory for itch and might
suggest that pain and itch should be investigated separately on the level of
neurons, mediators, and mechanisms. However, in addition to broadly overlapping
mediators of itch and pain, there is also evidence for overlapping functions in
primary afferents: nociceptive primary afferents can provoke itch when activated
very locally in the epidermis, and sensitization of both nociceptors and
pruriceptors has been found following local nerve growth factor application in
volunteers. Thus, also mechanisms that underlie the development of chronic itch
and pain including spontaneous activity and sensitization of primary afferents as
well as spinal cord sensitization may well overlap to a great extent. Rather than
separating itch and pain, research concepts should therefore address the common
mechanisms. Such an approach appears most appropriate for clinical conditions of
neuropathic itch and pain and also chronic inflammatory conditions. While itch
researchers can benefit from the large body of information of the pain field,
pain researchers will find behavioral readouts of spontaneous itch much simpler
than those for spontaneous pain in animals and the skin as source of the pruritic
activity much more accessible even in patients.
PMID- 25846625
TI - Organoborane catalyzed regioselective 1,4-hydroboration of pyridines.
AB - A bulky organoborane Ar(F)2BMe (Ar(F) = 2,4,6-tris(trifluoromethyl)phenyl, 1) has
been synthesized. In C6D6 solution this organoborane and pyridine form a
frustrated Lewis pair. Under mild conditions, 1 can efficiently catalyze 1,4
hydroboration of a series of pyridines. This reaction is highly chemo- and
regioselective. The reaction intermediate, a boronium complex
[Py2Bpin][Ar(F)2B(H)Me] (3), was characterized in solution by NMR spectroscopy,
which was also confirmed by DFT calculation.
PMID- 25846623
TI - Amygdala pain mechanisms.
AB - A limbic brain area, the amygdala plays a key role in emotional responses and
affective states and disorders such as learned fear, anxiety, and depression. The
amygdala has also emerged as an important brain center for the emotional
affective dimension of pain and for pain modulation. Hyperactivity in the
laterocapsular division of the central nucleus of the amygdala (CeLC, also termed
the "nociceptive amygdala") accounts for pain-related emotional responses and
anxiety-like behavior. Abnormally enhanced output from the CeLC is the
consequence of an imbalance between excitatory and inhibitory mechanisms.
Impaired inhibitory control mediated by a cluster of GABAergic interneurons in
the intercalated cell masses (ITC) allows the development of glutamate- and
neuropeptide-driven synaptic plasticity of excitatory inputs from the brainstem
(parabrachial area) and from the lateral-basolateral amygdala network (LA-BLA,
site of integration of polymodal sensory information). BLA hyperactivity also
generates abnormally enhanced feedforward inhibition of principal cells in the
medial prefrontal cortex (mPFC), a limbic cortical area that is strongly
interconnected with the amygdala. Pain-related mPFC deactivation results in
cognitive deficits and failure to engage cortically driven ITC-mediated
inhibitory control of amygdala processing. Impaired cortical control allows the
uncontrolled persistence of amygdala pain mechanisms.
PMID- 25846626
TI - Toxic effects of cadmium on flatworm stem cell dynamics: A transcriptomic and
ultrastructural elucidation of underlying mechanisms.
AB - Stem cells or undifferentiated cells can cope more easily with external stresses.
To evaluate the impact of toxic compounds on stem cell dynamics in vivo, in
relation to other biological responses, we use the carcinogenic element cadmium
and the regenerating model organism Macrostomum lignano. Through both BrdU and
anti-histone H3 immunostainings, cadmium-induced effects were investigated at
different stages of the stem cell cycle. A 24-h exposure to 100 and 250 MUM CdCl2
significantly decreased the number of stem cells (neoblasts) in mitosis, whereas
the number of cells in the S phase remained unchanged. After this short-term
exposure, the ultrastructure of the neoblasts was minimally affected in contrast
to the epidermal tissues. These results were supported by gene expression data:
transcripts of cdc2 and pig3 were significantly upregulated during all
treatments. Both genes are involved in the cell cycle progression and are
transcribed in the gonadal region, where stem cells are highly represented. Based
on a substantial increase in gene expression of heat shock proteins (HSP) and
their high activity in the gonadal region, we hypothesize that these proteins are
key players in the protection of stem cells against external stresses. Apart from
the strong HSP induction, other protective processes including cell division,
apoptosis and anti-oxidative defence, were also activated. We, therefore,
conclude that the protection of stem cells against external stressors may be
based on the interplay between stem cell maintenance, i.e. repair and recovery
through division, on one hand and apoptosis on the other hand. (c) 2015 Wiley
Periodicals, Inc. Environ Toxicol 31: 1217-1228, 2016.
PMID- 25846627
TI - Improved energy bound accuracy enhances the efficiency of continuous protein
design.
AB - Flexibility and dynamics are important for protein function and a protein's
ability to accommodate amino acid substitutions. However, when computational
protein design algorithms search over protein structures, the allowed flexibility
is often reduced to a relatively small set of discrete side-chain and backbone
conformations. While simplifications in scoring functions and protein flexibility
are currently necessary to computationally search the vast protein sequence and
conformational space, a rigid representation of a protein causes the search to
become brittle and miss low-energy structures. Continuous rotamers more closely
represent the allowed movement of a side chain within its torsional well and have
been successfully incorporated into the protein design framework to design
biomedically relevant protein systems. The use of continuous rotamers in protein
design enables algorithms to search a larger conformational space than previously
possible, but adds additional complexity to the design search. To design large,
complex systems with continuous rotamers, new algorithms are needed to increase
the efficiency of the search. We present two methods, PartCR and HOT, that
greatly increase the speed and efficiency of protein design with continuous
rotamers. These methods specifically target the large errors in energetic terms
that are used to bound pairwise energies during the design search. By tightening
the energy bounds, additional pruning of the conformation space can be achieved,
and the number of conformations that must be enumerated to find the global
minimum energy conformation is greatly reduced.
PMID- 25846628
TI - Amino acid-based surfactants - do they deserve more attention?
AB - The 20 standard amino acids (together with a few more that are not used in the
biosynthesis of proteins) constitute a versatile tool box for synthesis of
surfactants. Anionic, cationic and zwitterionic amphiphiles can be prepared and
surfactants with several functional groups can be obtained by the proper choice
of starting amino acid. This review gives examples of procedures used for
preparation and discusses important physicochemical properties of the amphiphiles
and how these can be taken advantage of for various applications. Micelles with a
chiral surface can be obtained by self-assembly of enantiomerically pure
surfactants and such supramolecular chirality can be utilized for asymmetric
organic synthesis and for preparation of mesoporous materials with chiral pores.
Surfactants based on amino acids with two carboxyl groups are effective chelating
agents and can be used as collectors in mineral ore flotation. A surfactant based
on cysteine readily oxidizes into the corresponding cystine compound, which can
be regarded as a gemini surfactant. The facile and reversible cysteine-cystine
transformation has been taken advantage of in the design of a switchable
surfactant. A very attractive aspect of surfactants based on amino acids is that
the polar head-group is entirely natural and that the linkage to the hydrophobic
tail, which is often an ester or an amide bond, is easily cleaved. The rate of
degradation can be tailored by the structure of the amphiphile. The ester linkage
in betaine ester surfactants is particularly susceptible to alkaline hydrolysis
and this surfactant type can be used as a biocide with short-lived action. This
paper is not intended as a full review on the topic. Instead it highlights
concepts that are unique to amino acid-based surfactants and that we believe can
have practical implications.
PMID- 25846629
TI - Development of a nurse-assisted preanesthesia evaluation program for pediatric
outpatient anesthesia.
AB - BACKGROUND: Historically, anesthesiologists have conducted preanesthesia
evaluation, but more recently, nurse practitioners (NPs) are increasingly
assisting with the preanesthesia evaluation of children. In the current economic
environment for healthcare, strategies to provide superior outcomes and
exceptional patient experience at the lowest possible cost are constantly being
explored. We examined whether well trained nurses, working alongside NPs, could
safely and effectively assist in preanesthesia evaluation. The aim of this
quality improvement project was to implement a new model for preanesthesia
evaluation for healthy outpatient pediatric patients: nurse-assisted
preanesthesia evaluation (NAPE). METHODS: Using quality improvement methods, Key
Driver Diagrams and SMART aims gave direction for the training and clinical
implementation of this new process. Using small tests of change and Plan-Do-Study
Act cycles, we developed a training process and a stepwise process to integrate
them into the clinical work flow. The primary outcome measure was the proportion
of the total preanesthesia evaluations in which the Anesthesia Nurses assisted.
To ensure quality and safety, data on balancing measures and quality metrics were
collected. RESULTS: The weekly percentage of outpatients evaluated by Anesthesia
Nurses increased from 0% to 55% within the first 4 months and was then sustained.
The remaining patients were evaluated by the Anesthesia NPs. The balancing
measures did not show any significant negative effect. Our perioperative quality
metrics were also not changed significantly. CONCLUSION: Using quality
improvement methods, we successfully improved the utilization of staff resources
by adding an Anesthesia Nurse-assisted preanesthesia evaluation program alongside
our NPs to provide outstanding preanesthesia care at the lowest possible cost.
PMID- 25846630
TI - Removal of bisphenol derivatives through quinone oxidation by polyphenol oxidase
and subsequent quinone adsorption on chitosan in the heterogeneous system.
AB - In this study, the combined use of a biopolymer chitosan and an oxidoreductase
polyphenol oxidase (PPO) was systematically investigated for the removal of
bisphenol derivatives from aqueous medium. The process parameters, such as the pH
value, temperature, and PPO concentration, were estimated to conduct the
enzymatic quinone oxidation of bisphenol derivatives by as little enzyme as
possible. Bisphenol derivatives effectively underwent PPO-catalysed quinone
oxidation without H2O2 unlike other oxidoreductases, such as peroxidase and
tyrosinase, and the optimum conditions were determined to be pH 7.0 and 40
degrees C for bisphenol B, bisphenol E, bisphenol O, and bisphenol Z; pH 7.0 and
30 degrees C for bisphenol C and bisphenol F; and pH 8.0 and 40 degrees C for
bisphenol T. They were completely removed through adsorption of enzymatically
generated quinone derivatives on chitosan beads or chitosan powders. Quinone
adsorption on chitosan beads or chitosan powders in the heterogeneous system was
found to be a more effective procedure than generation of aggregates in the
homogeneous system with chitosan solution. The removal time was shortened by
increasing the amount of chitosan beads or decreasing the size of the chitosan
powders.
PMID- 25846631
TI - Spectrally selective imaging with wideband balanced steady-state free precession
MRI.
AB - PURPOSE: Unwanted, bright fat signals in balanced steady-state free precession
sequences are commonly suppressed using spectral shaping. Here, a new spectral
shaping method is proposed to significantly improve the uniformity of stopband
suppression without compromising the level of passband signals. METHODS: The
proposed method combines binomial-pattern excitation pulses with a wideband
balanced steady-state free precession sequence kernel. It thereby increases the
frequency separation between the centers of pass and stopbands by pi radians,
enabling improved water-fat contrast. Simulations were performed to find the
optimal flip angles and subpulse spacing for the binomial pulses that maximize
contrast and signal efficiency. RESULTS: Comparisons with a conventional binomial
balanced steady-state free precession sequence were performed in simulations as
well as phantom and in vivo experiments at 1.5 T and 3 T. Enhanced fat
suppression is demonstrated in vivo with an average improvement of 58% in blood
fat and 68% in muscle-fat contrast (P < 0.001, Wilcoxon signed-rank test).
CONCLUSION: The proposed binomial wideband balanced steady-state free precession
method is a promising candidate for spectrally selective imaging with enhanced
reliability against field inhomogeneities.
PMID- 25846632
TI - The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth
and metastases in vasopressin type 2 receptor-expressing breast cancer models.
AB - Desmopressin (dDAVP) is a safe haemostatic agent with previously reported
antitumour activity. It acts as a selective agonist for the V2 vasopressin
membrane receptor (V2r) present on tumour cells and microvasculature. The purpose
of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r
expressing preclinical mouse models of breast cancer. We assessed antitumour
effects of [V4Q5]dDAVP using human MCF-7 and MDA-MB-231 breast carcinoma cells,
as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer
cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle
distribution was analysed by flow cytometry. In order to study the effect of
intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast
cancer xenografts were generated in athymic mice. F3II cells were injected into
syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and
experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP
against breast cancer cells were greater than those of dDAVP, and associated with
V2r-activated signal transduction and partial cell cycle arrest. In MDA-MB-231
xenografts, [V4Q5]dDAVP (0.3 ug/kg, thrice a week) reduced tumour growth and
angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice
resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also
displayed greater antimetastatic efficacy than dDAVP on experimental lung
colonisation by F3II cells. The novel analogue was well tolerated in preliminary
acute toxicology studies, at doses >= 300-fold above that required for anti
angiogenic/antimetastatic effects. Our data establish the preclinical activity of
[V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further
clinical trials.
PMID- 25846633
TI - Ex vivo uranium decontamination efficiency on wounded skin and in vitro skin
toxicity of a calixarene-loaded nanoemulsion.
AB - The present work aims at studying the decontamination efficacy of a calixarene
loaded nanoemulsion on two ex vivo wounded skin models mimicking superficial
stings or cuts contaminated with uranium, and on a third model using excoriation.
The decontaminating formulation was compared with the currently used radio
decontaminating soapy water (Trait rouge(r)) treatment. Moreover, to assess skin
damage potentially induced by the undiluted nanoemulsion, in vitro toxicity
studies were conducted on an in vitro reconstructed human epidermis, coupled with
three different toxicity tests [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl
tetrazolium bromide, lactate dehydrogenase, and interleukin-1-alpha]. This work
demonstrated not only a significant decontamination activity of the calixarene
nanoemulsion on wounded skin, ranging from 92% to 94% of the applied uranium
solution according to the ex vivo model used, but also the absence of side
effects of this promising treatment.
PMID- 25846634
TI - A SNP test to identify Africanized honeybees via proportion of 'African'
ancestry.
AB - The honeybee, Apis mellifera, is the world's most important pollinator and is
ubiquitous in most agricultural ecosystems. Four major evolutionary lineages and
at least 24 subspecies are recognized. Commercial populations are mainly derived
from subspecies originating in Europe (75-95%). The Africanized honeybee is a New
World hybrid of A. m. scutellata from Africa and European subspecies, with the
African component making up 50-90% of the genome. Africanized honeybees are
considered undesirable for bee-keeping in most countries, due to their extreme
defensiveness and poor honey production. The international trade in honeybees is
restricted, due in part to bans on the importation of queens (and semen) from
countries where Africanized honeybees are extant. Some desirable strains from the
United States of America that have been bred for traits such as resistance to the
mite Varroa destructor are unfortunately excluded from export to countries such
as Australia due to the presence of Africanized honeybees in the USA. This study
shows that a panel of 95 single nucleotide polymorphisms, chosen to differentiate
between the African, Eastern European and Western European lineages, can detect
Africanized honeybees with a high degree of confidence via ancestry assignment.
Our panel therefore offers a valuable tool to mitigate the risks of spreading
Africanized honeybees across the globe and may enable the resumption of queen and
bee semen imports from the Americas.
PMID- 25846645
TI - Knowledge, understanding, and uptake of noninvasive prenatal testing among Latina
women.
AB - OBJECTIVE: The aim of this study is to assess Latina patient understanding of
noninvasive prenatal testing (NIPT) and identify what factors influence
uptake/refusal to NIPT to adapt counseling to the needs and interests of this
population. METHODS: Mixed-methods survey in English and Spanish administered to
pregnant Latina patients throughout pregnancy. RESULTS: Sixty-three women
participated in our study (67% response rate); 34.9% chose to do NIPT, and 65.1%
declined. Approximately half of participants (44%) had an NIPT knowledge score of
<=3 out of six total questions. Two of the most significant factors influencing
uptake of NIPT were a higher reported educational level (p = 0.015) and a higher
NIPT knowledge score (p = 0.014); 42.9% of participants knew that NIPT only
screens for certain chromosomal conditions; 39% of women who declined NIPT would
never consider NIPT in the future. CONCLUSIONS: One-third of Latina women elected
NIPT; a higher reported educational level and language were most predictive of
this choice. Overall knowledge was significantly lower for women who declined
NIPT. Lower knowledge may suggest that not all women are making informed
decisions because of varying degrees of informed consent. Providing culturally
tailored information can help women navigate the complexities of prenatal testing
in order to make decisions most aligned with their values.
PMID- 25846646
TI - Subchronic administration of riparin III induces antidepressive-like effects and
increases BDNF levels in the mouse hippocampus.
AB - Riparin III (Rip III) is an alcamide isolated from Aniba riparia that has
presented effects of antidepressant and anxiolytic activities in acute stress
behavioral models. The trial's goal was to investigate the activity of Rip III in
mice exposed to corticosterone-induced chronic depression model. Swiss female
mice, 22-25 g, were distributed in following experimental groups: control group
(vehicle1: saline containing 0.1% dimethyl sulfoxide and 0.1% Tween-80, SC+
vehicle 2: distilled water emulsified with 2% Tween-80, PO); stressed group
(corticosterone, 20 mg/kg, SC, + vehicle 2, orally); Rip III group (50 mg/kg,
orally); and fluvoxamine (Flu) group (50 mg/kg, orally). The mice were exposed to
the behavioral tests, and posteriorly, Brain-derived neurotrophic factor protein
levels were assessed in hippocampal samples. Statistical analysis of the data was
performed by one-way anova, followed by Newman-Keuls test. Both administrations
of Rip III and Flu significantly reduced the immobility time in tail suspension
and forced swimming tests after 21 days without affecting locomotor function.
There was also an increase in BDNF protein levels in the mice hippocampus. These
findings further support the hypothesis that Rip III could be a new
pharmacological target for the treatment of mood disorders.
PMID- 25846647
TI - Effects of treatment with androgen receptor ligands on microRNA expression of
prostate cancer cells.
AB - Post-transcriptional regulation by microRNA (miRNA) is an important aspect of
androgen receptor (AR) signalling in prostate cancer cells. However, the global
profiling of miRNA expression in prostate cancer cells following treatment with
AR ligands has not been reported so far. In this study we examined the effect of
treatment with two AR agonists (mibolerone (MIB) and dihydrotestosterone (DHT))
and an AR antagonist (bicalutamide (BIC)) on miRNA expression in the human
androgen-dependent LNCaP prostate cancer cell line using microarray technology
and verification of selected miRNA using quantitative real-time PCR (qRT-PCR). No
miRNA was identified as differentially expressed following treatment with the AR
antagonist BIC. In contrast, a number of common and compound-specific alterations
in miRNA expression were observed following treatment with AR agonists.
Unexpectedly it was found that treatment with the AR agonists resulted in the
repression of miR-221, a miRNA previously established to be involved with
prostate cancer development. This observation indicates that this miRNA may have
a more complex role in prostate cancer development than considered previously.
Treatment with MIB led to an induction of miR-210 expression, a hypoxia-related
miRNA. This miRNA is reported to be involved in cell adaptation to hypoxia and
thus induction in conditions of normoxia may be important in driving metabolic
changes observed in prostate cancer. Thus examining the effect of AR agonists and
antagonists on miRNA expression can provide novel insights into the response of
cells to AR ligands and subsequent downstream events.
PMID- 25846648
TI - Deconstructing chronic low back pain in the older adult--step by step evidence
and expert-based recommendations for evaluation and treatment: part I: Hip
osteoarthritis.
AB - OBJECTIVE: To present the first in a series of articles designed to deconstruct
chronic low back pain (CLBP) in older adults. The series presents CLBP as a
syndrome, a final common pathway for the expression of multiple contributors
rather than a disease localized exclusively to the lumbosacral spine. Each
article addresses one of twelve important contributors to pain and disability in
older adults with CLBP. This article focuses on hip osteoarthritis (OA). METHODS:
The evaluation and treatment algorithm, a table articulating the rationale for
the individual algorithm components, and stepped-care drug recommendations were
developed using a modified Delphi approach. The Principal Investigator, a five
member content expert panel and a nine-member primary care panel were involved in
the iterative development of these materials. The algorithm was developed keeping
in mind medications and other resources available within Veterans Health
Administration (VHA) facilities. As panelists were not exclusive to the VHA, the
materials can be applied in both VHA and civilian settings. The illustrative
clinical case was taken from one of the contributor's clinical practice. RESULTS:
We present an algorithm and supportive materials to help guide the care of older
adults with hip OA, an important contributor to CLBP. The case illustrates an
example of complex hip-spine syndrome, in which hip OA was an important
contributor to disability in an older adult with CLBP. CONCLUSIONS: Hip OA is
common and should be evaluated routinely in the older adult with CLBP so that
appropriately targeted treatment can be designed.
PMID- 25846649
TI - Hepatorenal syndrome: The last pieces of the puzzle or not yet?
PMID- 25846650
TI - IL-33-induced JNK pathway activation confers gastric cancer chemotherapy
resistance.
AB - Inflammation is regarded as one of the major hallmarks of tumors, and has a very
close relationship with gastric cancer. Interleukin-33 (IL-33), a new member of
the IL-1 family, plays an important role in both inflammatory disease and tumors.
The present study was designed to explore the effects of IL-33 on the
proliferation, drug sensitivity, and the invasiveness of gastric cancer cells in
vitro. IL-33 at concentrations lower than 100 pg/ml did not alter the inhibitory
rate of gastric cancer cells. Moreover, IL-33 at these low concentrations
protected against platinum-induced apoptosis in various gastric cancer cell
lines, yet not in normal gastric epithelial cells. We also found that IL-33
increased the activation of the JNK pathway, and enhanced the expression of ST2.
Furthermore, SP600125, a selective inhibitor of the JNK pathway, significantly
blocked the protective effects of IL-33 in gastric cancer cells. In addition,
Matrigel invasion assay showed that IL-33 markedly promoted gastric cancer cell
invasion. In conclusion, the present study demonstrated that IL-33 protected
against platinum-induced apoptosis and promoted cell invasion via activation of
the JNK pathway in gastric cancer cells. In light of the prevalence of platinum
based chemotherapeutics in the treatment of gastric cancer, our results suggest
that the level of IL-33 should be monitored during the treatment of gastric
cancer, particularly when using platinum-based chemotherapeutics.
PMID- 25846651
TI - Morbidity and mortality in systolic heart failure also associated with raised
serum neprilysin levels.
PMID- 25846652
TI - Response to letter regarding "Increased serum HMGB1 level may predict the fatal
outcomes in patients with chronic heart failure".
PMID- 25846653
TI - Influence of ischemic postconditioning on myocardial dysfunction measured by
speckle tracking echocardiography in patients with ST-elevation myocardial
infarction.
PMID- 25846654
TI - Time-dependent effect of preinfarction angina pectoris and intermittent
claudication on mortality following myocardial infarction: A Danish nationwide
cohort study.
AB - BACKGROUND: As proxies for local and remote ischemic preconditioning, we examined
whether preinfarction angina pectoris and intermittent claudication influenced
mortality following myocardial infarction. METHODS: Using medical registries, we
conducted a nationwide population-based cohort study of all first-time myocardial
infarction patients in Denmark during 2004-2012 (n=70,458). We computed all-cause
and coronary mortality rate ratios (MRRs). We categorized time between
angina/claudication presentation and subsequent myocardial infarction as 0-14, 15
30, 31-90, and > 90 days. We adjusted for age, sex, coronary intervention,
comorbidities, and medication use. RESULTS: Among all myocardial infarction
patients, 18.4% had prior angina and 3.8% had prior intermittent claudication.
Compared to patients without prior angina, the adjusted 30-day coronary MRR was
0.85 (95% confidence interval (CI): 0.80-0.92) for stable and 0.68 (95% CI: 0.58
0.79) for unstable angina patients. The mortality reduction increased when angina
presented close to myocardial infarction and was higher for unstable than for
stable angina. Thus, the 30-day coronary MRR was 0.72 (95% CI: 0.51-1.02) for
stable angina and 0.35 (95% CI: 0.17-0.73) for unstable angina presenting within
14 days before MI. The results were robust for all-cause mortality and in
numerous subgroups, including women, diabetics, patients treated with PCI, and
patients treated with and without cardioprotective drugs. Preinfarction
intermittent claudication was associated with higher short- and long-term
mortality compared to patients without intermittent claudication. CONCLUSIONS:
Preinfarction angina reduced 30-day mortality, particularly when unstable angina
closely preceded MI. Preinfarction intermittent claudication was associated with
increased short- and long-term mortality.
PMID- 25846655
TI - Effects of H. pylori infection on carotid intima-media thickness, serum glucose,
serum uric acid, liver and kidney function in subjects with chronic alcohol
ingestion.
PMID- 25846656
TI - Current profile of infective endocarditis in intravenous drug users: The
prognostic relevance of the valves involved.
PMID- 25846657
TI - New-onset atrial fibrillation may be a more important predictor of cardiac
mortality in acute myocardial infarction patients than preexisting atrial
fibrillation.
PMID- 25846659
TI - Acute myocardial infarction and sleep apnea.
PMID- 25846658
TI - Comparison of the effects of two low-density lipoprotein cholesterol goals for
secondary prevention after acute myocardial infarction in real-world practice: >=
50% reduction from baseline versus <70 mg/dL.
AB - BACKGROUND: The present study compared the effects of two low-density lipoprotein
cholesterol (LDL-C) goals for secondary prevention after acute myocardial
infarction (AMI) in real-world practice. METHODS AND RESULTS: Of 3091 consecutive
patients with AMI who had baseline LDL-C levels >= 70 mg/dL and underwent
successful percutaneous coronary intervention, 1305 eligible patients who
received discharge statin prescriptions were analyzed. Patients were categorized
into 2 groups according to the values of LDL-C at 1 year in two different manners
using percent reduction from baseline (>= 50% reduction, n=428 versus <50%
reduction, n=877) and fixed levels (< 70 mg/dL, n=625 versus >= 70 mg/dL, n=680).
The primary outcome was defined by the composite of 2-year major cardiac events
including cardiac death, non-fatal myocardial infarction, percutaneous coronary
intervention, and coronary artery bypass grafting after hospital discharge. At 2
years, major cardiac events occurred in 139 patients (10.7%). Compared with <50%
LDL-C reduction from baseline, patients with >= 50% LDL-C reduction had a 47%
risk reduction in major cardiac events (adjusted hazard ratio, 0.53; 95%
confidence interval, 0.36 to 0.79; P=0.002). But, compared with LDL-C levels >=
70 mg/dL at 1 year, patients with LDL-C levels < 70 mg/dL at 1 year had a similar
risk of major cardiac events (adjusted hazard ratio, 0.96; 95% confidence
interval, 0.68 to 1.34; P=0.793). CONCLUSIONS: Obtaining a >= 50% reduction in
LDL-C was associated with better clinical outcomes after AMI in real-world
practice, whereas achieving a < 70 mg/dL was not.
PMID- 25846660
TI - Impacts of valve intervention on the Functional REServe of the Heart: The FRESH
valve pilot study.
AB - PURPOSE: Severe valve lesions require corrective interventions to avoid
progression to heart failure (HF) and premature demise. We tested the hypothesis
that despite operative risks, corrective valvular interventions will lead to
significant improvements in overall cardiac pump function, especially before the
onset of cardiac decompensation. METHODS: We compared the cardiopulmonary
exercise performance and non-invasive haemodynamics of 46 consecutive patients
with severe valvular disease before and after valvular intervention with
reference to 101 healthy male and 139 female controls without cardiovascular
disease. Cardiac and physical functional reserves were measured with standard
respiratory gas analyses and CO2 rebreathing to measure cardiac output non
invasively during peak treadmill exercise. Data are given as mean +/- SD and
statistical significance accepted at P<0.05. RESULTS: The entire patient cohort
showed no significant improvement in peak O2 consumption (VO2max, P=0.74) or in
peak cardiac power (CPOmax, P=0.34) after valvular intervention, but we found
instead a dichotomous outcome depending on preoperative cardiac function: (i) the
pre-operative cardiac decompensatory subgroup (LoW, n=26) showed increased CPOmax
(2.63 +/- 0.67 to 3.42 +/- 0.98 W, P<0.0001) and VO2max (1.38 +/- 0.55 to 1.56 +/
0.59 L.min(-1), P<0.01); and (ii) the pre-operative non-decompensatory subgroup
(HiW) showed reduced CPOmax (4.58 +/- 0.96 to 3.84 +/- 0.92 W, P<0.001) and
VO2max (2.29 +/- 0.72 to 1.97 +/- 0.75 L.min(-1), P<0.01). Changes in NYHA class
were found to be discrepant with these objective measurements. CONCLUSION: This
investigation found an unexpected finding that valvular interventions performed
in routine clinical practice do not consistently improve cardiac function,
especially in those without pre-operative cardiac decompensation. Assessing
cardiac functional gains would open up new avenues for future trials of valvular
interventions.
PMID- 25846661
TI - Ticagrelor increases endothelial progenitor cell level compared to clopidogrel in
acute coronary syndromes: A prospective randomized study.
AB - BACKGROUND: The clinical benefit of ticagrelor compared to clopidogrel in ACS
patients suggested off-target property. Such pleiotropic effect could be mediated
by circulating endothelial progenitor cells (EPC) which are critical for vascular
healing. We aimed to investigate the impact of ticagrelor on EPC in acute
coronary syndrome (ACS) patients undergoing percutaneous coronary intervention
(PCI). METHODS: We prospectively randomized 106 ACS patients to ticagrelor or
clopidogrel. Sub-populations of CD34+ circulating progenitor cells (PC) were
analyzed by flow cytometry allowing one to determine the levels of CD34+ PC,
CD34+CD45+ Hematopoietic PC, CD34+133+ immature PC and CD34+KDR+ EPC on admission
and at 1 month. Changes in PC level were calculated as the difference between 1
month and baseline value. RESULTS: The 2 groups were similar regarding baseline
characteristics including PC numbers on admission. The 2 groups had similar
change in overall CD34+ PC and hematopoietic CD34+45+ PC level (p=0.2). On the
contrary, when considering CD34+133+ PC and CD34+KDR+ EPC, we observed that
patients treated by ticagrelor had a significantly higher increase in levels of
these PC subtypes compared to those treated by clopidogrel (0.23 (-0.33; 0.79) vs
0.00 (-0.5; 0.34); p=0.04 and 0.01 (-0.04; 0.05) vs -0.01 (-0.06; 0.03); p=0.02).
Changes in the level of CD34+CD133+ PC correlated with platelet activity measured
by the VASP index (r=-0.30; p=0.008). By contrast the increase in the level of
CD34+KDR+ EPC in the ticagrelor group was independent of platelet activity.
CONCLUSIONS: Ticagrelor increases the number of EPC in ACS patients suggesting a
benefit on endothelial regeneration that may participate in the pleiotropic
property of the drug.
PMID- 25846662
TI - Left anterior descending coronary artery fistula to left ventricle: The revenge
of a well treated myocardial infarction in the era of primary percutaneous
angioplasty.
PMID- 25846663
TI - Ticagrelor related dyspnea in patients with acute coronary syndromes: Incidence
and implication on ticagrelor withdrawn.
PMID- 25846664
TI - Below the poverty line and non-communicable diseases in Kerala: The Epidemiology
of Non-communicable Diseases in Rural Areas (ENDIRA) study.
AB - INTRODUCTION: India carries the greatest burden of global non-communicable
diseases (NCDs). Poverty is strongly associated with NCDs but there are few
prevalence studies which have measured poverty in India, particularly in rural
settings. METHODS: In Kerala, India, a population of 113,462 individuals was
identified. The "Epidemiology of Non-communicable Diseases in Rural Areas"
(ENDIRA) study was conducted via ASHAs (Accredited Social Health Activists).
Standardised questionnaires were used in household interviews of individuals
>=18years during 2012 to gather sociodemographic, lifestyle and medical data for
this population. The Government of Kerala definition of "the poverty line" was
used. The association between below poverty line (BPL) status, NCDs and risk
factors was analysed in multivariable regression models. RESULTS: 84,456 adults
were included in the analyses (25.4% below the poverty line). The prevalence of
NCDs was relatively common: myocardial infarction (MI) 1.4%, stroke 0.3%,
respiratory diseases 5.0%, and cancer 1.1%. BPL status was not associated with
age (p=0.96) or gender (p=0.26). Compared with those above the poverty line
(APL), the BPL group was less likely to have diabetes, hypertension or
dyslipidaemia (p<0.0001), and more likely to smoke (p<0.0001). Compared with APL,
BPL was associated with stroke (OR 1.33, 1.04-1.69; p=0.02) and respiratory
disease (OR 1.23, 1.15-1.32; p<0.0001) in multivariable analyses, but not MI or
cancer. CONCLUSIONS: In rural Kerala, BPL status was associated with stroke and
respiratory diseases, but not with MI and cancer although it was associated with
smoking status, compared with above poverty line status.
PMID- 25846665
TI - Reasons for non-adherence to practice guidelines on stroke prevention in patients
with atrial fibrillation: A cross-sectional study in primary care.
PMID- 25846666
TI - Bailout left main bioresorbable vascular scaffolding for the treatment of
iatrogenic coronary dissection induced by guiding catheter and sticky ABSORB
bioresorbable vascular scaffold balloon.
PMID- 25846667
TI - Novel presentation of Pompe disease: Inclusion-body myositis-like clinical
phenotype.
PMID- 25846668
TI - Damage to the insula is associated with abnormal interpersonal trust.
AB - Reciprocal trust is a crucial component of cooperative, mutually beneficial
social relationships. Previous research using tasks that require judging and
developing interpersonal trust has suggested that the insula may be an important
brain region underlying these processes (King-Casas et al., 2008). Here, using a
neuropsychological approach, we investigated the role of the insula in reciprocal
trust during the Trust Game (TG), an interpersonal economic exchange. Consistent
with previous research, we found that neurologically normal adults reciprocate
trust in kind, i.e., they increase trust in response to increases from their
partners, and decrease trust in response to decreases. In contrast, individuals
with damage to the insula displayed abnormal expressions of trust. Specifically,
these individuals behaved benevolently (expressing misplaced trust) when playing
the role of investor, and malevolently (violating their partner's trust) when
playing the role of the trustee. Our findings lend further support to the idea
that the insula is important for expressing normal interpersonal trust, perhaps
because the insula helps to recognize risk during decision-making and to identify
social norm violations.
PMID- 25846670
TI - Response to "Cryolipolysis: The Importance of Scientific Evaluation of a New
Technique".
PMID- 25846669
TI - Adoptive T cell therapy combined with intralesional administrations of TG1042
(adenovirus expressing interferon-gamma) in metastatic melanoma patients.
AB - Tumor immune escape has recently been shown to be related to the development of
an immune tolerance state of the microenvironment. Cytokines activating the
immune system such as IFN-gamma can be used to reverse the immune escape and thus
to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18
stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes
(TILs) in combination with intratumoral TG1042 injection (adenovirus expressing
IFN-gamma). The primary objective was to investigate the safety of treatment.
Secondary objectives were to study the clinical response and translational
research. The treatment was well tolerated. Among the 13 patients evaluable for
tumor response, 38.5% had an overall objective response (OOR = CR + PR) and
disease control rate (DCR = CR + PR + S) of 46%. The clinical response of the 37
targeted lesions led to an OOR of 51% and a DCR of 75%. Translational research on
predictive markers did not significantly differ between responder and non
responder patients. However, specifically regarding injected lesions, the
clinical response correlated with CD3-/CD56+ NK cells which could be activated by
TG1042. Further larger studies of this combined immunotherapy are needed to
confirm our findings. Intralesional TG1042 combined with antigen-selected TILs
should be discussed.
PMID- 25846671
TI - Pulmonary mycobacterial spindle cell pseudotumor in a lung transplant patient:
progression without therapy and response to therapy.
AB - Mycobacterial spindle cell pseudotumor (MSP) represents a rare, non-malignant,
mass-forming reaction to various mycobacterial infections, typically occurring in
immunocompromised patients. It is characterized by the proliferation of spindle
shaped fibrohistiocytic cells without the formation of epithelioid granulomas.
Without staining for acid-fast bacilli, histological distinction from other
spindle cell lesions, including malignancy, can be difficult. Most of the MSP
cases reported in the literature have involved lymph nodes, skin, spleen, or bone
marrow, but rarely involve the lung. MSP predominately occurs in patients who are
immunosuppressed. We present a patient with MSP of the transplanted lung caused
by non-tuberculous mycobacteria, in whom both the natural course of the untreated
pseudotumor as well as the response to antimycobacterial treatments were
observed.
PMID- 25846672
TI - Incidence and weight trajectories of binge eating disorder among young women in
the community.
AB - OBJECTIVE: To assess the population prevalence and incidence of binge eating
disorder (BED) among young women. METHOD: In a nationwide longitudinal study of
Finnish twins born 1975-1979, the women participated in five surveys from age 16
until their mid-thirties. At Wave 4 (mean age 24 years), the women (N = 2,825)
underwent a 2-stage screening for eating disorders. We assessed the lifetime
prevalence, incidence, and clinical characteristics of DSM-5 BED. RESULTS: We
detected 16 women who met DSM-5 criteria for BED, yielding a lifetime prevalence
of 0.7% (95% confidence interval [CI] 0.4-1.2%). The incidence of BED among women
between 10 and 24 years of age was 35 (95% CI 20-60) per 100,000 person-years.
The mean age of onset of BED was 19 years (range 13-27 years). Of the cases,
13/16 (81%) were currently ill. Duration of illness at the time of assessment
ranged from less than a year to 13 years (median 6 years). Of women with BED,
only two had a history of other eating disorders, but six had lifetime major
depressive disorder. Two-thirds of the women with BED belonged to the highest
weight quartile at age 16, and their mean BMI at age 22-27 year was 26.2 kg/m(2)
(range 22.1-32.5 kg/m(2)). DISCUSSION: Incident BED as defined by DSM-5 was
relatively rare among younger women and was often preceded by relative
overweight. BED often occurred without a history of other eating disorders, but
comorbidity with major depressive disorder was common.
PMID- 25846673
TI - Complete myocardial revascularization confers a larger clinical benefit when
performed with state-of-the-art techniques in high-risk patients with multivessel
coronary artery disease: A meta-analysis of randomized and observational studies.
AB - OBJECTIVES: To test whether a strategy of complete revascularization (CR) as
compared with incomplete myocardial revascularization (IR)-both performed with
current "state-of-the-art" percutaneous coronary interventions (PCI) or coronary
artery bypass graft (CABG)-would provide a clinical benefit in patients with
multivessel coronary artery disease (MVCAD). BACKGROUND: The "optimal" extent of
myocardial revascularization remains to be determined. METHODS: We performed a
meta-analysis of studies reporting on clinical outcomes of MVCAD patients treated
with CR and IR, with extensive (>80%) use of stents for PCI or arterial conduits
in CABG. Relative risk (RR) and 95% confidence intervals (CIs) for all-cause
mortality were assessed as primary endpoint, myocardial infarction (MI) and
repeat revascularization as secondary endpoints. RESULTS: A total of 28 studies
were identified, including 83,695 patients with 4.7 +/- 4.3 years of follow-up.
Compared with IR, CR was associated with reduced mortality (RR: 0.73; 95% CI 0.66
0.81) both after CABG (RR: 0.76; 95% CI 0.63-0.90) and PCI (RR: 0.73; 95% CI 0.64
0.82). The risks of MI (RR: 0.74; 95% CI 0.64-0.85) and repeat revascularization
(RR: 0.77; 95% CI 0.66-0.88) were also lower after CR as compared with IR.
Metaregression showed a significant RR reduction of MI associated with more
recent publication (P = 0.021) and increasing prevalence of diabetes (P = 0.033).
CONCLUSIONS: In MVCAD, as compared with IR, CR confers a clinical benefit that
seems larger in cohorts of patients enrolled in more recent studies and with a
higher prevalence of diabetes. (c) 2015 Wiley Periodicals, Inc.
PMID- 25846674
TI - RPL10 mutation segregating in a family with X-linked syndromic Intellectual
Disability.
AB - Intellectual disability is a neurodevelopmental disorder of impaired adaptive
skills and low intelligence quotient. The overall prevalence is estimated at 2-3%
in the general population with extreme clinical and genetic heterogeneity, and it
has been associated with possibly causative mutations in more than 700 identified
genes. In a recent review, among over 100 X-linked intellectual disability
causative genes, eight were reported as "awaiting replication." Exome sequencing
in a large family identified a missense mutation in RPL10 highly suggestive of X
linked intellectual disability. Herein, we report on the clinical description of
four affected males. All patients presented apparent intellectual disability
(4/4), psychomotor delay (4/4) with syndromic features including amniotic fluid
excess (3/4), microcephaly (2/4), urogenital anomalies (3/4), cerebellar syndrome
(2/4), and facial dysmorphism. In the literature, two mutations were reported in
three families with affected males presenting with autism. This report confirms
the implication of RPL10 mutations in neurodevelopmental disorders and extends
the associated clinical spectrum from autism to syndromic intellectual
disability.
PMID- 25846675
TI - Improved and versatile viral 2A platforms for dependable and inducible high-level
expression of dicistronic nuclear genes in Chlamydomonas reinhardtii.
AB - A significantly improved viral 2A peptide system for dependable high-level
expression of dicistronic genes in Chlamydomonas reinhardtii has been developed.
Data are presented demonstrating that use of an especially proficient 'extended
FMDV 2A' coding region allows production of two independent protein products from
a dicistronic gene with almost complete efficiency. Importantly, results are also
presented that demonstrate the utility of this 2A system for efficient high-level
expression of foreign genes in C. reinhardtii, which has not previously been
reliably achievable in this algal model system. To expand the versatility of the
2A expression system, a number of commonly used selectable marker proteins were
assessed for their compatibility with the extended FMDV 2A peptide. Additional
experiments demonstrate the feasibility and utility of 2A-containing dicistronic
systems that rely on a strong conditional promoter for transcriptional control
and a low-expression marker gene for selection. This strategy allows easy and
efficient delivery of genes of interest whose expression levels require
regulation either to mitigate potential toxicity or allow differential expression
under controlled experimental conditions. Finally, as an additional practical
demonstration of the utility of the extended FMDV 2A system, confocal
fluorescence microscopy is used to demonstrate that native and foreign proteins
of interest bearing post-translational remnants of the extended FMDV 2A peptide
localize correctly to various cellular compartments, including a striking
demonstration of the almost exclusive localization of the Rubisco small subunit
protein to the pyrenoid of the C. reinhardtii chloroplast in cells maintained
under ambient CO2 concentrations.
PMID- 25846676
TI - Electron-deficient fullerenes in triple-channel photosystems.
AB - Fullerenes of increasing electron deficiency are designed, synthesized and
evaluated in multicomponent surface architectures to ultimately build gradients
in LUMO levels with nine components over 350 meV down to -4.22 eV.
PMID- 25846677
TI - An Iron Oxide Nanocarrier Loaded with a Pt(IV) Prodrug and Immunostimulatory
dsRNA for Combining Complementary Cancer Killing Effects.
AB - There is major current interest in harnessing the immune system against cancer
and in developing drugs that provide complementary cancer killing mechanisms.
Although the recent advent of nanoparticle-based drug delivery systems has
improved the efficacy of platinum drugs for chemotherapy, one of the fundamental
paradigms in their design and use is evading surveillance by the immune system to
enhance anticancer efficacy. However, new studies are showing that chemotherapy
can profit from actively targeting stimulation of the immune system and that
suitably functionalized nanomaterials might be ideal for overcoming some key
challenges in immunotherapy. Pt(IV) prodrug-modified PEGylated phospholipid
micelles that encapsulate biocompatible iron oxide nanoparticles (IONPs) as a new
delivery system for cisplatin are reported. The Pt(IV)-IONPs are functionalized
with polyinosinic-polycytidylic acid (poly (I:C))--a double stranded RNA (dsRNA)
analog widely used as an adjuvant in clinical trials of cancer immunotherapy. The
Pt(IV)-IONPs and poly (I:C)--Pt(IV)-IONPs enhance by more than an order of
magnitude the prodrug cytotoxicity in different tumor cells, while greatly
increasing the ability of cisplatin and poly (I:C) to activate dendritic cells-
the key cellular players in immunotherapy. The results suggest that these
constructs hold promise for targeted chemoimmunotherapy.
PMID- 25846684
TI - Addressing requests for emergency ultrasonographic examinations when implementing
teleradiology services.
AB - PURPOSE: To prospectively assess how to address requests for ultrasonographic
examinations when setting up an on-call teleradiology service. MATERIALS AND
METHODS: An analytical prospective study was performed from January 2012 to
December 2012 inclusively. All requests received for after-hours ultrasonographic
examinations during this period were analyzed. Ultrasound requests were
classified as being postponable until working hours, replaceable by an alternate
cross-sectional imaging modality, or urgent and needing to be performed after
hours. RESULTS: A total of 176 requests for ultrasonographic examinations were
analyzed. They predominantly included requests for abdominal and pelvic
ultrasonographic examinations (63%). Thirty-nine requests (22.2%) were considered
as postponable, 49 (27.8%) as replaceable and 64 (36.4%) as both postponable and
replaceable. Twenty-four requests (13.6%) were considered as urgent; they
consisted of 10 requests for venous duplex Doppler ultrasonographic examinations
of the lower limbs, eight requests for testicular ultrasonographic examinations,
five for pelvic ultrasonographic examinations and one for soft-tissue
ultrasonographic examination. In these urgent cases, realistic options were
either to transfer the patient to another institution or to train emergency
department physicians in ultrasonography for local handling. CONCLUSION: Although
the need for addressing requests for ultrasonographic examinations should be
taken into account when setting up an on-call teleradiology service, it should
not impede such plans.
PMID- 25846685
TI - The difference in congenital cholesteatoma CT findings based on the type of mass.
AB - OBJECTIVE: A retrospective assessment of differences in congenital cholesteatoma
CT findings with a focus on type of cholesteatoma mass. MATERIALS AND METHODS:
The medical records and CT images of 14 patients with congenital cholesteatomas
in the middle ear who underwent surgery at our institution between January 2009
and July 2014 were reviewed. Cholesteatomas were classified as closed type, open
type, or mixed type based on intraoperative findings. The CT findings including
cholesteatoma size, location, and shape were retrospectively reviewed. RESULTS:
Eight patients had closed type cholesteatomas, four had mixed type, and two had
open type. The mean size of all cholesteatomas was 5.1mm. None of the
cholesteatoma types indicated a tendency towards a certain location. The round
shape was observed more frequently in closed type cholesteatomas than in other
types (closed: 5/8; mixed: 1/4; open: 0/2). Two large closed type cholseteatomas
and two mixed type cholesteatomas exhibited a constricted shape. Both of the open
type cholesteatomas displayed an irregular shape. CONCLUSION: Small closed type
congenital cholesteatomas were typically observed as round shaped lesions, but
large closed type cholesteatomas and other type cholesteatomas tended to display
shapes other than round.
PMID- 25846686
TI - Extra-intestinal malignancies in inflammatory bowel diseases: An update with
emphasis on MDCT and MR imaging features.
AB - Inflammatory bowel diseases (IBD) are associated with an increased risk of
gastrointestinal cancers and more specifically in sites affected by chronic
inflammation. However, patients with IBD have also an increased risk for
developing a variety of extra-intestinal cancers. In this regard, hepatobiliary
cancers, such as cholangiocarcinoma, are more frequently observed in IBD patients
because of a high prevalence of primary sclerosing cholangitis, which is
considered as a favoring condition. Extra-intestinal lymphomas, mostly non
Hodgkin lymphomas, and skin cancers are also observed with an increased incidence
in IBD patients by comparison with that in patients without IBD. This review
provides an update on demographics, risk factors and clinical features of extra
intestinal malignancies, including cholangiocarcinoma, hepatocellular carcinoma
and lymphoma, that occur in patients with IBD along with a special emphasis on
the multidetector row computed tomography and magnetic resonance imaging features
of these uncommon conditions.
PMID- 25846688
TI - An uncommon cause of left upper abdominal pain.
PMID- 25846689
TI - Epidermoid splenic cyst.
PMID- 25846690
TI - Association of ABCB1 C3435T polymorphism with phenobarbital resistance in Thai
patients with epilepsy.
AB - WHAT IS KNOWN AND OBJECTIVE: One-third of patients with epilepsy are resistant to
anti-epileptic drugs (AEDs). Drug-resistant epilepsy is believed to be
multifactorial involving both genetic and non-genetic factors. Genetic variations
in the ABCB1 gene encoding the drug efflux transporter, p-glycoprotein (p-gp),
may influence the interindividual variability in AED response by limiting drugs
from reaching their target. Phenobarbital (PB), one of the most cost-effective
and widely used AEDs in developing countries, has been reported to be transported
by p-gp. This study aimed to investigate the association of a genetic variant,
ABCB1 3435C>T, and non-genetic factors with phenobarbital response in Thai
patients with epilepsy. METHODS: One hundred and ten Thai patients with epilepsy
who were treated with PB maintenance doses were enrolled in this study. Two
phenotypic groups, PB-responsive epilepsy and PB-resistant epilepsy, were defined
according to the International League Against Epilepsy (ILAE) criteria. Subjects
were genotyped for ABCB1 3435C>T (rs1045642). Multiple logistic regression
analysis was tested for the association of ABCB1 3435C>T polymorphism and non
genetic factors with PB response. RESULTS AND DISCUSSION: Sixty-two PB-responsive
epilepsy subjects and 48 PB-resistant epilepsy subjects were identified. All
genotype frequencies of the ABCB1 3435C>T SNP were consistent with the Hardy
Weinberg equilibrium (P > 0.05). The ABCB1 3435C>T polymorphism and type of
epilepsy were associated with response to PB. Patients with PB-resistant epilepsy
had a significantly higher frequency of ABCB1 3435CC genotype and had focal
epilepsy more often than patients with PB-responsive epilepsy (adjusted OR =
3.962, 95% CI = 1.075-14.610, P-value = 0.039; adjusted OR = 5.936, 95% CI =
2.272-15.513, P-value < 0.001, respectively). The model explained 25.5% of the
variability in response to PB (R(2) = 0.255). WHAT IS NEW AND CONCLUSION: Thai
patients of ABCB1 3435CC genotype and with focal epilepsy were more often PB
resistant. Those two factors partly account for the variability in Thai epilepsy
patients' response to phenobarbital.
PMID- 25846696
TI - Can the height-independent Pottel eGFR equation be used as a screening tool for
chronic kidney disease in children?
AB - Determination of plasma creatinine (Pcr) should be associated to an estimation of
glomerular filtration rate (eGFR). Pottel et al. established a height-independent
equation, eGFR = 107.3/(Pcr/Q) where Q is the median of Pcr (Pottel-Belgium). The
aims were to 1) determine a local height-independent equation (Pottel-Lyon), 2)
evaluate the performance of these equations compared to the Schwartz 2009 and
Schwartz-Lyon equations, and 3) evaluate the height-independent equations in
laboratory routine. Therefore, 1) all first pediatric Pcr determination (December
2009-June 2011) were collected, and median of Pcr was determined for each 1-year
age interval (Q-Lyon), 2) GFR was measured (mGFR) in 359 children (438 measures)
and compared to eGFR, and 3) all first Pcr determination (January 2012-June 2013)
were used to calculate eGFR with the Pottel-Lyon and the Pottel-Belgium
equations. Pcr was determined by an IDMS-standardized enzymatic assay. In the
population with a mGFR, the Pottel-Lyon and the Schwartz-Lyon showed the best
performance (bias, P10 and P30). However, the performance in identifying patients
with a mGFR < 75 mL/min/1.73 m(2) was similar for all the studied equations.
CONCLUSION: The performance of the height-independent and dependent equations to
identify mild renal dysfunction is similar. The height-independent Pottel
equation could be proposed as an excellent screening tool for kidney disease when
height information is not available. " WHAT IS KNOWN: " * Determination of plasma
creatinine in children is rarely associated to an estimation of glomerular
filtration rate due to the lack of height information. * Pottel et al. developed
a height-independent equation (eGFR = 107.3/(Pcr/Q) where Q is the median of Pcr
for each age class. " WHAT IS NEW: " * The performance of the height-independent
(Pottel) or height-dependent (Schwartz) equations is similar to identify renal
dysfunction (GFR < 75 mL/min/1.73 m (2) ) in children. * The height-independent
Pottel equation could be an excellent screening tool for kidney disease in a
general pediatric laboratory when height information is not available.
PMID- 25846697
TI - Work stress, burnout, and perceived quality of care: a cross-sectional study
among hospital pediatricians.
AB - Poor hospital work environments affect physicians' work stress. With a focus on
hospital pediatricians, we sought to investigate associations between work
stress, burnout, and quality of care. A cross-sectional study was conducted in N
= 96 pediatricians of a German academic children's hospital (response rate = 73.8
%). All variables were assessed with standardized questionnaires. Multivariate
regression analyses were applied to investigate associations after adjusting for
potential confounders. Critically high work stress (effort/reward ratio, ERR >
1.0) was reported by N = 25 (28.4 %) participants. Pediatricians in inpatient
wards had significantly more work stress than their colleagues in intensive care
units and outpatient wards; 10.2 % of surveyed pediatricians reported critically
high burnout. Again, inpatient ward staff reported significantly increased
emotional exhaustion. After controlling for several confounders, we found that
pediatricians with high work stress and emotional exhaustion reported reduced
quality of care. Mediation analyses revealed that especially pediatricians'
emotional exhaustion partially mediated the effect of work stress on quality of
care. CONCLUSION: Results demonstrate close relationships between increased work
stress and burnout as well as diminished quality of care. High work stress
environments in pediatric care influence mental health of pediatricians as well
as quality of patient care. WHAT IS KNOWN: * The quality of pediatricians' work
environment in the hospital is associated with their work stress and burnout. *
The consequences of pediatricians' work life for the quality of care need to be
addressed in order to inform interventions to improve work life and care quality.
WHAT IS NEW: * Our study shows associations between increased work stress and
burnout with mitigated quality of care. * Beyond indirect effects of work stress
through emotional exhaustion on quality of care we also observed direct
detrimental effects of pediatricians' work stress on mitigated care quality.
PMID- 25846698
TI - Uterine rupture: trends over 40 years.
AB - OBJECTIVE: To follow trends of uterine rupture over a period of 40 years in
Norway. DESIGN: Population-based study using data from the Medical Birth
Registry, the Patient Administration System, and medical records. SETTING:
Norway. SAMPLE: Women giving birth in 21 maternity units in Norway during the
period 1967-2008 (n = 1 441 712 maternities). METHODS: The incidence and outcomes
of uterine rupture were compared across four decades: 1967-1977; 1978-1988; 1989
1999; and 2000-2008. Multivariable logistic regression was used to determine the
odds ratio (OR) for uterine rupture in each decade compared with the second
decade. MAIN OUTCOME MEASURE: Trends in uterine rupture. RESULTS: We identified
359 uterine ruptures. The incidence rates per 10 000 maternities in the first,
second, third, and fourth decade were 1.2, 0.9, 1.7, and 6.1, respectively. The
ORs for complete and partial ruptures in the fourth versus the second decade were
6.4 (95% confidence interval, 95% CI 3.8-10.8) and 7.2 (95% CI 4.2-12.3),
respectively. Significant contributing factors to this increase were the higher
rates of labour augmentation with oxytocin, scarred uteri from a previous
caesarean section, and labour induction with prostaglandins or prostaglandins
combined with oxytocin. After adjusting for risk factors, the ORs for complete
and partial ruptures were 2.2 (95% CI 1.3-3.8) and 2.8 (95% CI 1.6-4.8),
respectively. Severe postpartum haemorrhage, hysterectomy, intrapartum death and
infant death after complete uterine ruptures decreased significantly over time.
CONCLUSIONS: A sharply increasing trend of uterine rupture was found. Obstetric
interventions contributed to this increase, but could not explain it entirely.
TWEETABLE ABSTRACT: A sharply increasing trend of uterine ruptures has been found
in Norway in recent years.
PMID- 25846700
TI - A Cascade-Reaction Nanoreactor Composed of a Bifunctional Molecularly Imprinted
Polymer that Contains Pt Nanoparticles.
AB - This study was aimed at addressing the present challenge of cascade reactions,
namely, how to furnish the catalysts with desired and hierarchical catalytic
ability. This issue was addressed by constructing a cascade-reaction nanoreactor
made of a bifunctional molecularly imprinted polymer containing acidic catalytic
sites and Pt nanoparticles. The acidic catalytic sites within the imprinted
polymer allowed one specified reaction, whereas the encapsulated Pt nanoparticles
were responsible for another coupled reaction. To that end, the unique imprinted
polymer was fabricated by using two well-coupled templates, that is, 4
nitrophenyl acetate and 4-nitrophenol. The catalytic hydrolysis of the former
compound at the acidic catalytic sites led to the formation of the latter
compound, which was further reduced by the encapsulated Pt nanoparticles to 4
aminophenol. Therefore, this nanoreactor demonstrated a catalytic-cascade
ability. This protocol opens up the opportunity to develop functional catalysts
for complicated chemical processes.
PMID- 25846699
TI - Influenza virus antigenicity and broadly neutralizing epitopes.
AB - A vaccine formulation that would be effective against all strains of influenza
virus has long been a goal of vaccine developers, but antibodies after infection
or vaccination were seen to be strain specific and there was little evidence of
cross-reactive antibodies that neutralized across subtypes. Recently a number of
broadly neutralizing monoclonal antibodies have been characterized. This review
describes the different classes of broadly neutralizing antibodies and discusses
the potential of their therapeutic use or for design of immunogens that induce a
high proportion of broadly neutralizing antibodies.
PMID- 25846701
TI - Prevalence of Psychiatric Disorders Among Turkish Children: The Effects of
Impairment and Sociodemographic Correlates.
AB - This study was designed to assess the prevalence of psychiatric disorders and the
impact of impairment criteria on rates of diagnoses in a representative sample of
elementary school children from a country in a region. We sampled 419 primary
school children by using a one-stage design in Izmir, Turkey. The response rate
was 99.5 % and 417 cases were assessed using the Schedule for Affective Disorders
and Schizophrenia for School-Age Children Present and Lifetime Version and a
scale to assess the impairment criterion. The results showed that 36.7 % of the
sample met DSM-IV criteria independent of impairment and that 14.1 % of the
population had one or more DSM-IV disorders when a measure of impairment specific
to each diagnosis was considered. The most prevalent disorders were attention
deficit/hyperactivity disorder and anxiety disorders. This study provided the
first estimates of the prevalence of specific DSM-IV-defined psychiatric
disorders in Turkish population of children.
PMID- 25846702
TI - Weight estimation in paediatric resuscitation: A hefty issue in New Zealand.
AB - OBJECTIVE: To test the accuracy of weight estimation methods currently used in
New Zealand to predict a child's weight in emergency resuscitation. METHODS: A
prospective, observational study. Data were collected in July 2013 at five
Auckland schools among children aged 5-10 years. Collected demographic
information included age, ethnicity, sex and school decile. Standardised measures
included weight, height and Broselow-Luten tape (2011 version, limited to
children 43-143 cm) weight. Age-based weight estimates were calculated for APLS,
Shann and Theron formulae. Mean bias (actual weight - estimated weight) and
clinical accuracy (proportion of estimates within 10% of actual weight) are
reported. Bland-Altman plots illustrate agreement and 95% limits of agreement.
RESULTS: The 376 participants weighed between 14.2 and 93.1 kg. The proportion of
weight estimates within 10% of actual weight were 28.7%, 39.1% and 45.7% for the
age-based formula (Theron, APLS and Shann, respectively). The mean bias was
negative for Theron (-6.5) and positive for APLS (7.8) and Shann (7.7). For the
length-based Broselow-Luten tape method (n = 305), the proportion of weight
estimates within 10% of actual weight was 73.4% and mean bias was 1.1.
CONCLUSION: For children under 143 cm in height, the Broselow-Luten tape
outperforms other weight estimation methods, accurately estimating weight in
approximately three out of four children. The age-based estimation methods
performed poorly overall, with variation by age and ethnicity.
PMID- 25846703
TI - Stepping up, stepping back, stepping forward: Student nurses' experiences as peer
mentors in a pre-nursing scholarship.
AB - Mentorship is an essential part of the registered nurse's role, yet few
opportunities exist for student nurses to mentor others during pre-registration
programmes. This paper reports student nurses' experiences of mentoring school
pupils during a pre-nursing scholarship. Focus groups were conducted with fifteen
final year student nurses (14 female, 1 male) in two university campuses in
Scotland. Discussions were audio recorded and transcribed verbatim, and data
analysed thematically. Three interconnected themes emerged: 1) stepping up; 2)
stepping back; 3) stepping forward. 'Stepping up' was a process through which
student nurses rapidly assumed responsibility for mentoring pupils, facilitated
through the attitudes and actions of students' mentors and students' control over
pupils' practice experiences. 'Stepping back' encapsulated attitudes and
behaviours that enabled student nurses to mentor pupils that involved
considerable judgement around how unfolding events in practice could provide
learning and development opportunities, and emotional acuity to support pupils
through, sometimes challenging, practice situations. 'Stepping forward' described
how students' mentoring experience allowed them to appraise and affirm nursing
knowledge and skills, and gain greater appreciation of the reality and complexity
of mentorship in clinical practice. Peer mentoring may prepare student nurses for
future mentoring roles and aid their transition into clinical practice.
PMID- 25846704
TI - Generation of Helios reporter mice and an evaluation of the suppressive capacity
of Helios(+) regulatory T cells in vitro.
AB - Helios is a member of the Ikaros transcription factor family and has been
reported to be a marker of thymus-derived regulatory T cells (Treg). Helios is an
intracellular protein, however, and hence cannot be used as a marker to separate
living Tregs. To solve this problem, we generated Helios reporter mice in which
Helios+ cells selectively express Venus, a variant of green fluorescent protein.
Most of the Tregs in the thymus expressed Helios, whereas its expression was
varied in peripheral lymphoid organs. The Helios+ Treg-population was superior in
ability to suppress both antigen-specific and TCR-stimulated T cell responses. We
also showed that Helios+ Tregs inhibited the cytokine production by T cells more
efficiently than Helios- Tregs. We conclude that Helios reporter mouse strain is
a useful tool to study function of Helios and that Helios+ Tregs represent the
highly suppressive population.
PMID- 25846705
TI - The GO4KIDDS Brief Adaptive Scale.
AB - BACKGROUND: Accurate measurement of adaptive behaviour is important in both
clinical and research contexts. While several good clinical measures exist, as
well as brief research measures for adults with intellectual disability, there is
need for a brief and efficient measure for research with children and youth. We
present preliminary psychometric properties of a new scale we developed for such
purposes, the GO4KIDDS Brief Adaptive Behaviour Scale. MATERIALS AND METHODS: A
large sample (n = 432) of parents of youth (aged 3-20) with intellectual
disability and/or ASD completed an online survey that included the new scale. A
subsample of these parents (n = 204) also completed the Scales of Independent
Behavior-Revised Short Form (Scales of Independent Behavior-Revised Comprehensive
Manual, 1996 and Riverside Publishing). RESULTS: The new scale has good internal
consistency and correlates strongly with the Scales of Independent Behavior, thus
supporting its reliability and validity. CONCLUSIONS: Although we do not
recommend its use for clinical purposes, the GO4KIDDS Brief Adaptive Behaviour
Scale may be useful for survey research with parents of children and youth with
developmental disabilities.
PMID- 25846706
TI - Overlap of Juvenile polyposis syndrome and Cowden syndrome due to de novo
chromosome 10 deletion involving BMPR1A and PTEN: implications for treatment and
surveillance.
AB - We describe a patient with a severe juvenile polyposis phenotype, due to a de
novo deletion of chromosome 10q22.3-q24.1. He was initially diagnosed with
Juvenile polyposis syndrome (JPS) at age four after presenting with hematochezia
due to multiple colonic juvenile polyps. He then re-presented at 23 years with
recurrent hematochezia from juvenile polyps in his ileoanal pouch. He is one of
the earliest reported cases of JPS associated with a large deletion of chromosome
10. Since his initial diagnosis of JPS further studies have confirmed an
association between JPS and mutations in BMPR1A in chromosome band 10q23.2, which
is in close proximity to PTEN. Mutations in PTEN cause Cowden syndrome (CS) and
other PTEN hamartoma tumor syndromes. Due to the chromosome 10 deletion involving
contiguous portions of BMPR1A and PTEN in our patient, he may be at risk for CS
associated cancers and features, in addition to the polyps associated with JPS.
This case presents new challenges in developing appropriate surveillance
algorithms to account for the risks associated with each syndrome and highlights
the importance of longitudinal follow-up and transitional care between pediatric
and adult gastroenterology for patients with hereditary polyposis syndromes.
PMID- 25846708
TI - Validation of 1-year predictive score of long-term response to interferon-beta in
everyday clinical practice multiple sclerosis patients.
AB - BACKGROUND AND PURPOSE: The Rio score (RS) and the modified Rio score (MRS) are
two scoring systems that can identify the early predictive factors of disability
progression in relapsing-remitting multiple sclerosis (RRMS) patients treated
with interferon-beta (IFN-beta). The objective of the study was to validate the
usefulness of the RS and MRS in a large cohort of multiple sclerosis patients
treated with IFN-beta in daily clinical practice. METHODS: The analysis included
a cohort of RRMS patients treated with different formulations of IFN-beta for at
least 1 year. The RS and MRS were used to classify the patients after 1 year of
treatment. Multivariate analysis was performed to identify predictive variables
of suboptimal response at 5 years, defined as Expanded Disability Status Scale
confirmed progression or switching to a second-line therapy. RESULTS: Sixty-nine
of 416 included patients were considered as suboptimal responders at 5-year
evaluation. The possible score range was 0-3. A higher risk of suboptimal
response was found for RS and MRS in the presence of >=2 scores (hazard ratio
3.0, P = 0.002, and hazard ratio 5.0, P < 0.0001, respectively). CONCLUSIONS: Our
study confirmed, in a daily clinical setting, that MRS had a better specificity
and accuracy than RS in identifying the patients who will have a poor response to
long-term IFN-beta treatment.
PMID- 25846707
TI - Siglec receptors impact mammalian lifespan by modulating oxidative stress.
AB - Aging is a multifactorial process that includes the lifelong accumulation of
molecular damage, leading to age-related frailty, disability and disease, and
eventually death. In this study, we report evidence of a significant correlation
between the number of genes encoding the immunomodulatory CD33-related sialic
acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in
mammals. In keeping with this, we show that mice lacking Siglec-E, the main
member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E
causes the development of exaggerated signs of aging at the molecular,
structural, and cognitive level. We found that accelerated aging was related both
to an unbalanced ROS metabolism, and to a secondary impairment in detoxification
of reactive molecules, ultimately leading to increased damage to cellular DNA,
proteins, and lipids. Taken together, our data suggest that CD33rSiglecs co
evolved in mammals to achieve a better management of oxidative stress during
inflammation, which in turn reduces molecular damage and extends lifespan.
PMID- 25846710
TI - The Association Between Spontaneous Hyperventilation, Delayed Cerebral Ischemia,
and Poor Neurological Outcome in Patients with Subarachnoid Hemorrhage.
AB - BACKGROUND: The frequency and associations of spontaneous hyperventilation in
subarachnoid hemorrhage (SAH) are unknown. Because hyperventilation decreases
cerebral blood flow, it may exacerbate delayed cerebral ischemia (DCI) and worsen
neurological outcome. METHODS: This is a retrospective analysis of data from a
prospectively collected cohort of SAH patients at an academic medical center.
Spontaneous hyperventilation was defined by PaCO2 <35 mmHg and pH >7.45 and
subdivided into moderate and severe groups. Clinical and demographic
characteristics of patients with and without spontaneous hyperventilation were
compared using chi (2) or t tests. Bivariate and multivariable logistic
regression analyses were conducted to examine the association of moderate and
severe hyperventilation with DCI and discharge neurological outcome. RESULTS: Of
207 patients, 113 (55 %) had spontaneous hyperventilation. Spontaneously
hyperventilating patients had greater illness severity as measured by the Hunt
Hess, World Federation of Neurosurgical Societies (WFNS), and SAH sum scores.
They were also more likely to develop the following complications: pneumonia,
neurogenic myocardial injury, systemic inflammatory response syndrome (SIRS),
radiographic vasospasm, DCI, and poor neurological outcome. In a multivariable
logistic regression model including age, gender, WFNS, SAH sum score, pneumonia,
neurogenic myocardial injury, etiology, and SIRS, only moderate [odds ratio (OR)
2.49, 95 % confidence interval (CI) 1.10-5.62] and severe (OR 3.12, 95 % CI 1.30
7.49) spontaneous hyperventilation were associated with DCI. Severe spontaneous
hyperventilation (OR 4.52, 95 % CI 1.37-14.89) was also significantly associated
with poor discharge outcome in multivariable logistic regression analysis.
CONCLUSION: Spontaneous hyperventilation is common in SAH and is associated with
DCI and poor neurological outcome.
PMID- 25846709
TI - Global monitoring in the neurocritical care unit.
AB - Effective methods of monitoring the status of patients with neurological injuries
began with non-invasive observations and evolved during the past several decades
to include more invasive monitoring tools and physiologic measures. The
monitoring paradigm continues to evolve, this time back toward the use of less
invasive tools. In parallel, the science of monitoring began with the global
assessment of the patient's neurological condition, evolved to focus on regional
monitoring techniques, and with the advent of enhanced computing capabilities is
now moving back to focus on global monitoring. The purpose of this session of the
Second Neurocritical Care Research Conference was to collaboratively develop a
comprehensive understanding of the state of the science for global brain
monitoring and to identify research priorities for intracranial pressure
monitoring, neuroimaging, and neuro-electrophysiology monitoring.
PMID- 25846712
TI - High-intensity focused ultrasound treatment of placenta accreta after vaginal
delivery: a preliminary study.
AB - OBJECTIVE: To evaluate the safety and efficiency of high-intensity focused
ultrasound (HIFU) in the treatment of placenta accreta after vaginal delivery.
METHODS: Enrolled into this study between September 2011 and September 2013 were
12 patients who had been diagnosed with placenta accreta following vaginal
delivery and who had stable vital signs. All patients were treated using an
ultrasound-guided HIFU treatment system. As indication of the effectiveness of
the treatment we considered decreased vascular index on color Doppler imaging,
decrease in size of residual placenta compared with pretreatment size on
assessment by three-dimensional ultrasound with Virtual Organ Computer-aided
Analysis, reduced signal intensity and degree of enhancement on magnetic
resonance imaging and avoidance of hysterectomy following treatment. To assess
the safety of HIFU treatment, we recorded side effects, hemorrhage, infection,
sex steroid levels, return of menses and subsequent pregnancy. Patients were
followed up in this preliminary study until December 2013. RESULTS: The 12
patients receiving HIFU treatment had an average postpartum hospital stay of 6.8
days and an average period of residual placental involution of 36.9 days. HIFU
treatment did not apparently increase the risk of infection or hemorrhage and no
patient required hysterectomy. In all patients menstruation recommenced after an
average of 80.2 days, and sex steroid levels during the middle luteal phase of
the second menstrual cycle were normal. Two patients became pregnant again during
the follow-up period. CONCLUSION: This preliminary study suggests that ultrasound
guided HIFU is a safe and effective non-invasive method to treat placenta accreta
patients after vaginal delivery who have stable vital signs and desire to
preserve fertility. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 25846713
TI - Ammonium increases Ca(2+) signalling and upregulates expression of Cav1.2 gene in
astrocytes in primary cultures and in the in vivo brain.
AB - AIM: The primary aim of this study was to identify the effects of hyperammonaemia
on functional expression of Cav1.2 L-type Ca(2+) channels in astroglia. METHODS:
Primary cultures of mouse astrocytes were used to study effects of chronic
treatment (1-5 days) with ammonium chloride, at 1, 3 and 5 mm on depolarization
induced increases in free cytosolic Ca(2+) concentration ([Ca(2+)]i , measured
with Fura-2 based microfluorimetry) in control conditions and following treatment
with the L-type Ca(2+) channel inhibitor, nifedipine, or with ryanodine receptor
inhibitor, ryanodine. Expression of Cav1.2 mRNA was identified with RT-PCR,
whereas protein content was determined by Western blotting. Sustained
hyperammonaemia in vivo was induced by daily injections of urease (33 units kg
body weight(-1), i.p.) for 3 days. RESULTS: Depolarization-induced [Ca(2+)]i
transients sensitive to nifedipine (peak of the response) and to ryanodine
(plateau phase) were significantly increased in astrocytes chronically exposed to
ammonium. The ammonium-induced increase in Ca(2+) influx in astrocytes resulted
from an upregulation of Cav1.2 channel's expression detected at mRNA and protein
levels. Increase in Cav1.2 expression was prevented by ouabain antagonist
canrenone. Similar upregulation of Cav1.2 gene expression was found in the brains
of adult mice subjected to intraperitoneal injection of urease. In transgenic
mice tagged with an astrocyte-specific or neurone-specific markers and treated
with intraperitoneal injections of urease, the fluorescence-activated cell
sorting of neurones and astrocytes demonstrated that Cav1.2 mRNA expression was
upregulated in astrocytes, but not in neurones. CONCLUSIONS: Ammonium-induced
deregulation of astroglial Ca(2+) signalling, is, in part, associated with
upregulation of Cav1.2 L-type calcium channels.
PMID- 25846711
TI - Data collection and interpretation.
AB - Patient monitoring is routinely performed in all patients who receive
neurocritical care. The combined use of monitors, including the neurologic
examination, laboratory analysis, imaging studies, and physiological parameters,
is common in a platform called multi-modality monitoring (MMM). However, the full
potential of MMM is only beginning to be realized since for the most part,
decision making historically has focused on individual aspects of physiology in a
largely threshold-based manner. The use of MMM now is being facilitated by the
evolution of bio-informatics in critical care including developing techniques to
acquire, store, retrieve, and display integrated data and new analytic techniques
for optimal clinical decision making. In this review, we will discuss the crucial
initial steps toward data and information management, which in this emerging era
of data-intensive science is already shifting concepts of care for acute brain
injury and has the potential to both reshape how we do research and enhance cost
effective clinical care.
PMID- 25846714
TI - Association of TAP1 and TAP2 genes with susceptibility to pulmonary tuberculosis
in Koreans.
AB - Tuberculosis remains an important public health problem in Koreans. However, very
few studies have reported on the genetic factors associated with TB
susceptibility in Koreans. The aim of this study was to elucidate the genetic
factors associated with susceptibility to pulmonary tuberculosis (PTB). We
investigated the transporter associated with antigen processing -1 (TAP1) and
TAP2 gene polymorphisms in 160 Korean PTB patients (categorized according to
extent of lesion and TB medication history) and 210 controls. TAP2*C/E frequency
was significantly increased in the PTB (pc = 0.004, OR = 2.28). TAP2*Bky2/C/E
were enriched in the retreated, far-advanced and total PTB compared with the
controls (pc = 0.015, OR = 3.27; pc = 0.019, OR = 2.56; pc = 2.8 * 10(-4) , OR =
2.42, respectively). In the comparison of TAP2 gene with the DRB1*08:03, which is
associated with TAP2*Bky2 and PTB in Koreans, we demonstrated the hierarchy of
these association factors. TAP2*C/E is independent factors as strong as
DRB1*08:03, and TAP2*C/E interacts with DRB1*08:03, resulting in a striking
combined association. Our results suggest that TAP2 gene has an association with
PTB susceptibility, the extent of the lesion or recurrence. These associations
are independent from and additive with DRB1*08:03.
PMID- 25846715
TI - Associations between sensation seeking and d-amphetamine reinforcement.
AB - BACKGROUND AND OBJECTIVES: While many individuals experiment with stimulants,
only a subset transition to abuse or dependence. One characteristic widely
associated with stimulant abuse vulnerability in general is sensation seeking
(SS), though less clear is how individuals' baseline SS may predict their
response to acute stimulant administration. METHODS: In this secondary analysis,
we examined associations between SS and d-AMPH choice and subjective response
among healthy male (n = 16) and female (n = 21) adults participating in an
outpatient laboratory study wherein they received repeated opportunities to
sample and choose between d-AMPH (5, 10, and 20 mg/70 kg) and placebo. RESULTS:
Among males, elevated baseline SS was associated with increased d-AMPH choice and
positive subjective effects at 5 and 10 mg/70 kg doses. Among females, there were
no significant associations between SS and d-AMPH choice or subjective effects.
DISCUSSION AND CONCLUSIONS: Elevated SS in males may be associated with increased
sensitivity to d-AMPH reinforcement and positive subjective effects. Data from
this study suggest that SS may not predict sensitivity to stimulants in females,
though future studies with larger sample sizes are necessary to answer this
definitively. SCIENTIFIC SIGNIFICANCE: Sensation seeking may reflect an important
characteristic underlying sensitivity to stimulant reinforcement. Efforts to
better understand these individual differences would inform efforts to identify
and intervene with those at risk for developing abuse or dependence.
PMID- 25846716
TI - Clinical presentation of human C1q deficiency: How much of a lupus?
AB - Hereditary human C1q deficiency has been well described to be associated with
high susceptibility for the development of systemic lupus erythematosus (SLE).
The majority of subjects present a clinical syndrome closely related to SLE.
However, limited information is available about the primary diagnosis and
particular clinical manifestations of SLE in this specific subgroup of patients.
In this review, we performed a comprehensive search of electronic databases up to
November 2014 to identify and analyze reports on patients with C1q deficiency. We
identified 71 C1q-deficient patients descending from 45 families that had been
published. According to the American College of Rheumatology (ACR) diagnostic
criteria for SLE 39/71 (55%) subjects could be classified as having SLE. Another
16/71 (22.5%) presented a SLE-like syndrome (defined as 3 positive ACR criteria)
whereas in 16/71 (22.5%) no SLE could be diagnosed at time of publication.
Symptoms began at a median age of 5 years, male and females being equally
affected. Discoid rash (56% versus 10%, p<0.001) and oral ulcers (49% versus 24%,
p<0.001) occurred significantly more frequent in C1q deficiency-associated
SLE/SLE-like disease than in sporadic SLE, whereas arthritis (38% versus 84%,
p<001) and anti-ds-DNA (18% versus 78%, p<0.001) occurred less frequently. Renal
and neurological manifestations were found to occur similarly frequent. The
severe course of disease in some patients seemed to be mostly due to severe
infections at early ages and not in particular due to more aggressive SLE
manifestations.
PMID- 25846717
TI - Dressed to impress: impact of environmental adaptation on the Candida albicans
cell wall.
AB - Candida albicans is an opportunistic fungal pathogen of humans causing
superficial mucosal infections and life-threatening systemic disease. The fungal
cell wall is the first point of contact between the invading pathogen and the
host innate immune system. As a result, the polysaccharides that comprise the
cell wall act as pathogen associated molecular patterns, which govern the host
pathogen interaction. The cell wall is dynamic and responsive to changes in the
external environment. Therefore, the host environment plays a critical role in
regulating the host-pathogen interaction through modulation of the fungal cell
wall. This review focuses on how environmental adaptation modulates the cell wall
structure and composition, and the subsequent impact this has on the innate
immune recognition of C. albicans.
PMID- 25846719
TI - Gut microbiome composition and metabolomic profiles of wild western lowland
gorillas (Gorilla gorilla gorilla) reflect host ecology.
AB - The metabolic activities of gut microbes significantly influence host physiology;
thus, characterizing the forces that modulate this micro-ecosystem is key to
understanding mammalian biology and fitness. To investigate the gut microbiome of
wild primates and determine how these microbial communities respond to the host's
external environment, we characterized faecal bacterial communities and, for the
first time, gut metabolomes of four wild lowland gorilla groups in the Dzanga
Sangha Protected Areas, Central African Republic. Results show that geographical
range may be an important modulator of the gut microbiomes and metabolomes of
these gorilla groups. Distinctions seemed to relate to feeding behaviour,
implying energy harvest through increased fruit consumption or fermentation of
highly fibrous foods. These observations were supported by differential abundance
of metabolites and bacterial taxa associated with the metabolism of cellulose,
phenolics, organic acids, simple sugars, lipids and sterols between gorillas
occupying different geographical ranges. Additionally, the gut microbiomes of a
gorilla group under increased anthropogenic pressure could always be
distinguished from that of all other groups. By characterizing the interplay
between environment, behaviour, diet and symbiotic gut microbes, we present an
alternative perspective on primate ecology and on the forces that shape the gut
microbiomes of wild primates from an evolutionary context.
PMID- 25846718
TI - Essential Role of Interleukin-12/23p40 in the Development of Graft-versus-Host
Disease in Mice.
AB - Graft-versus-host disease (GVHD), in both its acute (aGVHD) and chronic (cGVHD)
forms, remains a major obstacle impeding successful allogeneic hematopoietic stem
cell transplantation (allo-HSCT). T cells, in particular pathogenic T helper (Th)
1 and Th17 subsets, are a driving force for the induction of GVHD. IL-12 and IL
23 cytokines share a common p40 subunit and play a critical role in driving Th1
differentiation and in stabilizing the Th17 phenotype, respectively. In our
current study, we hypothesized that p40 is an essential cytokine in the
development of GVHD. By using p40-deficient mice, we found that both donor- and
host-derived p40 contribute to the development of aGVHD. Neutralization of p40
with an anti-p40 mAb inhibited Th1- and Th17-polarization in vitro. Furthermore,
anti-p40 treatment reduced aGVHD severity while preserving the graft-versus
leukemia (GVL) activity. Alleviation of aGVHD was associated with an increase of
Th2 differentiation and a decrease of Th1 and Th17 effector T cells in the GVHD
target organs. In addition, anti-p40 treatment attenuated the severity of
sclerodermatous cGVHD. These results provide a strong rationale that blockade of
p40 may represent a promising therapeutic strategy in preventing and treating
aGVHD and cGVHD while sparing the GVL effect after allo-HSCT.
PMID- 25846720
TI - Mechanical suction for clot evacuation: experience with "suction bridge" for safe
and effective clot removal.
AB - OBJECTIVES: To present the experience with the use of a "suction bridge" for
removal of bladder clots. METHODS: In all patients presenting with bladder clots,
mechanical suction was done using a "suction bridge". This bridge has a luer lock
that is fixed to the cystoscope sheath, and the other end is connected to suction
tube. The suction pressure was started at 250 mmHg and was increased up to 400
mmHg if needed. RESULTS: Twenty patients with a mean age of 59.4 years were
included. The etiologies of bladder clots included bladder tumor in nine, benign
prostate hyperplasia (BPH) in two, BPH with bladder stone in one, hematochyluria
in three, and post-transurethral prostate resection in 10. Eighteen patients
presented in clot retention. The estimated clot size ranged from 50 mL to more
than 1 L. The mean duration for clot removal was 15 min (range 5-60). The
procedure was successful in all patients. There was no bladder injury. The
limitations include the small number of recruits, the non-randomized nature of
study, and no control group for comparison. CONCLUSION: Mechanical suction is
another safe, fast, and effective option of clot removal from the urinary
bladder. The suction bridge is useful while using this method.
PMID- 25846722
TI - Synthesis, characterization and antimicrobial activity of water-soluble silver(i)
complexes of metronidazole drug and selected counter-ions.
AB - A series of water-soluble silver(i) complexes of the type [Ag(MTZ)2X] [MTZ = 1-(2
hydroxyethyl)-2-methyl-5-nitro-1H-imidazole (metronidazole drug); X = NO3(-),
ClO4(-), CF3COO(-), BF4(-) and CH3SO3(-)] was synthesised by the reactions of
various Ag(i) salts with metronidazole (MTZ). All the complexes were
characterized by ESI-MS spectrometry, solution NMR ((1)H and (13)C) and IR
spectroscopy, and elemental analysis. Further evidence for the formation and
molecular structure of all the complexes was provided by X-ray single-crystal
crystallography. The different counter ions affect the crystal packing of the
complexes and thus have an impact on the final geometries. The antimicrobial
activities of the complexes against two Gram-positive strains: Staphylococcus
aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, three Gram-negative
strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922, Proteus
hauseri ATCC 13315 and yeast Candida albicans ATCC 10231 were evaluated and
compared with antibacterial and antifungal properties of appropriate silver
salts, metronidazole and silver sulfadiazine drugs. The newly synthesized
compounds exhibited significant antibacterial activity against Gram-positive
bacteria, better than the referenced silver sulfadiazine. The best active
silver(i)-metronidazole complex contains a methanesulphonate counter-ion.
Moreover, the complex inhibited the growth of yeast Candida albicans at a
concentration 3-fold lower than that required for silver sulfadiazine. In
addition, the complexes containing a tetrafluoroborate and a perchlorate as
counter-ions were characterized as effective antibacterial agents against the
tested Gram-negative bacteria.
PMID- 25846721
TI - One-year sustained glycaemic control and less hypoglycaemia with new insulin
glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using
basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including
6-month extension.
AB - AIMS: To evaluate the maintenance of efficacy and safety of insulin glargine 300
U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) in people with type 2 diabetes
mellitus (T2DM) using basal plus meal-time insulin for 12 months in the EDITION 1
trial. METHODS: EDITION 1 was a multicentre, randomized, open-label, two-arm,
phase IIIa study. Participants completing the initial 6-month treatment period
continued to receive Gla-300 or Gla-100, as previously randomized, once daily for
a further 6-month open-label extension phase. Changes in glycated haemoglobin
(HbA1c) and fasting plasma glucose concentrations, insulin dose, hypoglycaemic
events and body weight were assessed. RESULTS: Of 807 participants enrolled in
the initial phase, 89% (359/404) assigned to Gla-300 and 88% (355/403) assigned
to Gla-100 completed 12 months. Glycaemic control was sustained in both groups
(mean HbA1c: Gla-300, 7.24%; Gla-100, 7.42%), with more sustained HbA1c reduction
for Gla-300 at 12 months: least squares mean difference Gla-300 vs Gla-100: HbA1c
-0.17 [95% confidence interval (CI) -0.30 to -0.05]%. The mean daily basal
insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100.
Lower percentages of participants had >=1 confirmed [<=3.9 mmol/l (<=70 mg/dl)]
or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [24 h;
86 vs 92%; relative risk 0.94 (95% CI 0.89-0.99)] and during the night [54 vs
65%; relative risk 0.84 (95% CI 0.75-0.94)], while the annualized rates of such
hypoglycaemic events were similar. No between-treatment differences in adverse
events were apparent. CONCLUSION: During 12 months of treatment of T2DM requiring
basal and meal-time insulin, glycaemic control was better sustained and fewer
individuals reported hypoglycaemia with Gla-300 than with Gla-100. The mean basal
insulin dose was higher with Gla-300 compared with Gla-100, but total numbers of
hypoglycaemic events and overall tolerability did not differ between treatments.
PMID- 25846723
TI - Connecting nursing leadership and patient outcomes: state of the science.
PMID- 25846725
TI - Wellness among US adolescents ages 12-17 years.
AB - BACKGROUND: Wellness is a multidimensional construct related to an individual's
physical, emotional, intellectual and social well-being. We present estimates of
wellness among US adolescents aged 12-17 years and explore how demographic
characteristics are associated with wellness. METHODS: All respondents aged 12 to
17 years (n = 34,601) from the 2011-2012 National Survey of Children's Health
were included in the sample. Survey items were coded to operationalize an overall
wellness score, comprised of four subdimensions (physical, intellectual,
emotional and social). RESULTS: The mean adjusted overall wellness score was 30.2
(out of 40). Mean raw subdimensions scores were: social = 3.14 (out of 4),
emotional = 4.79 (out of 6), intellectual = 4.80 (out of 8) and physical = 6.57
(out of 8). Older adolescents, those with special health needs, those in lower
income families and those whose mother or father report fair-poor mental health
status had lower wellness scores. CONCLUSIONS: US adolescents have wellness
scores towards the upper or higher end of our scale. Several adolescent and
family characteristics were associated with either lower overall wellness and/or
lower wellness on multiple subdimensions. Assessing wellness during critical
developmental periods of adolescence is a first step towards promoting behaviours
that support increased wellness into adulthood.
PMID- 25846724
TI - Lovastatin-Mediated Changes in Human Tendon Cells.
AB - Statins are among the most widely prescribed drugs worldwide. Numerous studies
have shown their beneficial effects in prevention of cardiovascular disease
through cholesterol-lowering and anti-atherosclerotic properties. Although some
statin patients may experience muscle-related symptoms, severe side effects of
statin therapy are rare, primarily due to extensive first-pass metabolism in the
liver. Skeletal muscles appear to be the main site of side effects; however,
recently some statin-related adverse effects have been described in tendon. The
mechanism behind these side effects remains unknown. This is the first study that
explores tendon-specific effects of statins in human primary tenocytes. The cells
were cultured with different concentrations of lovastatin for up to 1 week. No
changes in cell viability or morphology were observed in tenocytes incubated with
therapeutic doses. Short-term exposure to lovastatin concentrations outside the
therapeutic range had no effect on tenocyte viability; however, cell migration
was reduced. Simvastatin and atorvastatin, two other drug family members, also
reduced the migratory properties of the cells. Prolonged exposure to high
concentrations of lovastatin induced changes in cytoskeleton leading to cell
rounding and decreased levels of mRNA for matrix proteins, but increased BMP-2
expression. Gap junctional communication was impaired but due to cell shape
change and separation rather than direct gap junction inhibition. These effects
were accompanied by inhibition of prenylation of Rap1a small GTPase.
Collectively, we showed that statins in a dose-dependent manner decrease
migration of human tendon cells, alter their expression profile and impair the
functional network, but do not inhibit gap junction function.
PMID- 25846726
TI - Prehospital care and transportation of pediatric trauma patients.
AB - BACKGROUND: Despite advances in prehospital emergency medical services (EMS),
most advocate "scoop-and-run" over "stay-and-play." However, there are almost no
studies in children. We hypothesize that the transportation of mortally injured
children is delayed and that the performance of prehospital interventions (PHIs)
themselves delay transportation and worsen outcomes in pediatric trauma patients.
MATERIALS AND METHODS: A total of 1884 admissions (<=17-y-old) transported via
EMS to a level 1 trauma center from January 2000-December 2012 were reviewed.
Propensity scores were assigned based on the need for a PHI (intubation and
resuscitation). PHI and non-PHI cohorts were matched 1:1 to compare outcomes.
Data are expressed as mean +/- standard deviation or median (interquartile
range). RESULTS: The population was 11 +/- 6 y, 70% male, 50% black, 76% blunt
injury, injury severity score 13 +/- 12, length of stay 3 (7) d, and mortality
3.6%. Incident to EMS arrival was 38 (20) min, EMS on-scene time was 14 (12) min,
and overall time of arrival to hospital was 27 (15) min. Patients that were
mortally wounded, despite having significantly higher rates of PHI, still had
similar transportation times to those who survived. Mostly every measure of
injury severity was worse in those who required PHI. When these factors were
corrected, EMS on-scene time was 18 (13) versus 14 (13) min (P = 0.551), EMS
arrival at the hospital was 31 (16) versus 28 (12) min (P = 0.292), length of
stay was 5 (15) versus 4 (12) d (P = 0.368), and mortality was 31.7% versus 28.3%
(P = 0.842) for PHI and non-PHI matched cohorts. CONCLUSIONS: PHIs did not delay
transportation times or worsen outcomes in pediatric trauma patients. Although
mortally injured children more often required PHIs, this did not delay
transportation to the trauma center.
PMID- 25846727
TI - p85alpha is a microRNA target and affects chemosensitivity in pancreatic cancer.
AB - BACKGROUND: We previously identified a correlation between increased expression
of the phosphoinositide 3-kinase (PI3K) regulatory subunit p85alpha and improved
survival in human pancreatic ductal adenocarcinoma (PDAC). The purpose of this
study was to investigate the impact of changes in p85alpha expression on response
to chemotherapy and the regulation of p85alpha by microRNA-21 (miR-21). MATERIALS
AND METHODS: PDAC tumor cells overexpressing p85alpha were generated by viral
transduction, and the effect of p85alpha overexpression on sensitivity to
gemcitabine was tested by MTT assay. Primary human PDAC tumors were stained for
p85alpha and miR-21 via immunohistochemistry and in situ hybridization,
respectively. Additionally, PDAC cells were treated with miR-21 mimic, and
changes in p85alpha and phospho-AKT were assessed by Western blot. Finally, a
luciferase reporter assay system was used to test direct regulation of p85alpha
by miR-21. RESULTS: Higher p85alpha expression resulted in increased sensitivity
to gemcitabine (P < 0.01), which correlated with decreased PI3K-AKT activation.
Human tumors demonstrated an inverse correlation between miR-21 and p85alpha
expression levels (r = -0.353, P < 0.001). In vitro, overexpression of miR-21
resulted in decreased levels of p85alpha and increased phosphorylation of AKT.
Luciferase reporter assays confirmed the direct regulation of p85alpha by miR-21
(P < 0.01). CONCLUSIONS: Our results demonstrate that p85alpha expression is a
determinant of chemosensitivity in PDAC. Additionally, we provide novel evidence
that miR-21 can influence PI3K-AKT signaling via its direct regulation of
p85alpha. These data provide insight into potential mechanisms for the known
relationship between increased p85alpha expression and improved survival in PDAC.
PMID- 25846728
TI - Microparticles impact coagulation after traumatic brain injury.
AB - BACKGROUND: The pathophysiology that drives the subacute hypercoagulable state
commonly seen after traumatic brain injury (TBI) is not well understood.
Alterations caused by TBI in platelet and microparticle (MP) numbers and function
have been suggested as possible causes; however, the contributions of platelets
and MPs are currently unknown. MATERIALS AND METHODS: A weight-drop technique of
TBI using a murine model of moderate head injury was used. Blood was collected at
intervals after injury. MP enumeration and characterization were performed using
Nanoparticle Tracking Analysis, and platelet counts and coagulation parameters
were determined using thromboelastometry. A MP procoagulant assay was used to
compare activity between injured and sham mice. RESULTS: At 24 h after injury,
there were no changes in circulating platelet numbers. However, there was a
decrease in platelet contribution to clot formation. In contrast, there was a
decline in circulating total MP numbers. When MPs from sham mice were added to
the blood from head-injured animals, there was a normalization of platelet
contribution to clot formation. Conversely, when MPs from TBI mice were added to
sham blood, there was a significant decrease in platelet contribution to clot
formation. Notably, there was an increase in MP procoagulant activity in head
injured mice. CONCLUSIONS: MPs generated after TBI likely contribute to altered
coagulation after head injury and may play a key role in the development of a
posttraumatic hypercoagulable state in TBI patients.
PMID- 25846729
TI - Concentrations of retinol and tocopherols in the milk of cows supplemented with
conjugated linoleic acid.
AB - This study was performed to investigate the hypothesis that supplementation of
conjugated linoleic acid (CLA) changes the concentrations of retinol and
tocopherols in the milk of cows. To investigate this hypothesis, Holstein cows
received daily from 3 weeks ante-partum to 14 weeks post-partum either 172 g of a
CLA-free rumen-protected control fat (control group, n = 20) or the same amount
of a rumen-protected CLA fat, supplying 4.3 g of cis-9, trans-11 CLA and 3.8 g of
trans-10, cis-12 CLA per d (CLA group, n = 20). Milk samples (collected at weeks
1, 3, 5, 8 and 11 of lactation) were analysed for retinol, alpha- and gamma
tocopherol concentrations. Milk of cows supplemented with CLA had higher
concentrations of retinol (+34%), alpha-tocopherol (+44%) and gamma-tocopherol
(+21%) than milk of control cows (p < 0.05). The daily output of these vitamins
via milk was also greater in cows of the CLA group than in cows of the control
group (+36, 50 and 24% for retinol, alpha-tocopherol and gamma-tocopherol,
respectively, p < 0.05). In agreement with higher concentrations of tocopherols,
concentrations of thiobarbituric acid-reactive substances, determined in milk of
week 5, were lower in cows of the CLA group than in control cows, indicative of a
lower susceptibility of milk lipids to peroxidation. Plasma concentrations of
retinol and alpha-tocopherol, determined at 1 and 5 weeks post-partum, were not
different between the two groups of cows. In conclusion, this study shows that
supplementing dairy cows with a moderate amount of CLA causes an increase of the
concentrations of vitamins A and E in the milk and results in an increased output
of those vitamins via milk. These effects might be beneficial with respect to the
nutritional value of dairy products and the susceptibility of milk fat to
oxidative deterioration.
PMID- 25846730
TI - Australian hip surveillance guidelines for children with cerebral palsy: 5-year
review.
AB - AIM: To ensure hip surveillance guidelines reflect current evidence of factors
influencing hip displacement in children with cerebral palsy (CP). METHOD: A
three-step review process was undertaken: (1) systematic literature review, (2)
analysis of hip surveillance databases, and (3) national survey of orthopaedic
surgeons managing hip displacement in children with CP. RESULTS: Fifteen articles
were included in the systematic review. Quantitative analysis was not possible.
Qualitative review indicated hip surveillance programmes have decreased the
incidence of hip dislocation in populations with CP. The Gross Motor Function
Classification System was confirmed as the best indicator of risk for
displacement, and evidence was found of hip displacement occurring at younger
ages and in young adulthood. Femoral geometry, pelvic obliquity, and scoliosis
were linked to progression of hip displacement. A combined data pool of 3366
children from Australian hip surveillance databases supported the effectiveness
of the 2008 Consensus Statement to identify hip displacement early. The survey of
orthopaedic surgeons supported findings of the systematic review and database
analyses. INTERPRETATION: This review rationalized changes to the revised and
renamed Australian Hip Surveillance Guidelines for Children with Cerebral Palsy
2014, informing frequency of radiographic examination in lower risk groups and
continuation of surveillance into adulthood for adolescents with identified risk
factors.
PMID- 25846731
TI - MicroRNA-506 inhibits gastric cancer proliferation and invasion by directly
targeting Yap1.
AB - Increasing evidence indicates that microRNA (miR)-506 plays a vital role in
tumorigenesis; however, the role of miR-506 in gastric cancer (GC) is unclear and
needs further investigation. In the present study, we showed that the decrease in
the expression of miR-506 is associated with tumor size, pathological tumor node
metastasis (TNM) stage, and lymph node metastasis in 63 GC patient tumors. We
found that patients with lower expression of miR-506 had a poor prognosis than
that with the patients with high expression of miR-506. Notably, the ectopic
expression of miR-506 was sufficient to inhibit cell proliferation, invasion, and
epithelial-mesenchymal transition in the GC cells. Moreover, results from
luciferase reporter assays identified miR-506 as a direct regulator of Yes
associated protein 1 (Yap1). Reintroduction of Yap1 rescues miR-506-induced
effects on SGC-7901 cell proliferation and invasion. This function of miR
506/Yap1 axis is clinically significant, as the level of miR-506 is inversely
correlated with Yap1 mRNA expression in matched tissues. Thus, our study
demonstrates that miR-506 may act as a tumor suppressor in GC and that the miR
506/Yap1 axis may help us better understand the molecular mechanisms of GC
progression.
PMID- 25846732
TI - The M30 assay does not detect apoptosis in epithelial-derived cancer cells
expressing low levels of cytokeratin 18.
AB - The primary aim of this study was to compare measurement of apoptosis by M30
immunoreactivity (a biomarker for apoptosis) to other apoptosis assays
(morphological assessment of nuclei, Annexin-V-FITC staining, DNA fragmentation
and PARP cleavage) in vitro. Caspase-cleaved cytokeratin 18 (M30, ccK18) is only
produced in epithelial cells and is regarded as a pharmacodynamic biomarker of
apoptotic cell death because it is released from cells during apoptosis induced
by chemotherapeutic agents. However, we have observed false negative results
using this assay in clinical samples. Therefore, we tested its ability to
accurately detect apoptosis in a panel of lung cancer cell lines with a range of
clinically approved chemotherapeutic drugs. Three different non-small cell lung
cancer (NSCLC) cell lines (A549, H1299, PC3) were used to correlate M30 levels
with alternate apoptosis assays. Following successful induction of apoptosis, the
A549 cell line showed an increase in M30 levels along with other well-known
features of apoptosis, whilst H1299 and PC3 cell lines did not show an increase
in M30 levels, even when apoptosis was detected by other means. Further analysis
showed that H1299 and PC3 cell lines expressed much lower levels of cytokeratin
18 protein compared to the A549 cell line. Our results suggest that reliable
detection of apoptosis via the M30 assay only works when sufficient levels of
cytokeratin 18 are present in the cells. This means that the M30 assay may result
in false negative results for apoptosis, and as such, the ELISA should be used in
conjunction with other assays.
PMID- 25846733
TI - ObRb downregulation increases breast cancer cell sensitivity to tamoxifen.
AB - Leptin is a potent adipokine that plays an important role in the progression of
breast cancer and interferes with the action of tamoxifen. We investigated the
molecular mechanism underlying the effect of leptin on tamoxifen resistance in
breast cancer cells that express leptin receptor (ObRb), and evaluated the impact
of ObRb suppression on tamoxifen treatment in MCF-7 and tamoxifen-resistant (TAM
R) cells. Leptin-induced signaling pathway activation was examined by qRT-PCR and
Western blotting. Chromatin immunoprecipitation assays were performed to further
examine the binding of estrogen receptor (ER) alpha on the promoter of cyclin D1
(CCND1) gene. The effects of combined ObRb knockdown and tamoxifen treatment were
evaluated in MCF-7 and TAM-R cells. We found that the enhanced proliferation
effects induced by leptin were related to extracellular-signal-regulated kinase
(ERK) 1/2 and signal transducers and activators of transcription (STAT) 3
signaling pathway activation and CCND1 upregulation. Leptin enhanced CCND1 gene
transcription by inducing the binding of ERalpha to the promoter of CCND1 gene.
ObRb knockdown significantly enhanced the inhibitory effects of tamoxifen on TAM
R cell proliferation and survival. This study suggested that long-term endocrine
therapy facilitates leptin and ObRb overexpression in breast cancer cells, which
attenuates the inhibitory effect of tamoxifen by activating both the ERK1/2 and
STAT3 signaling pathways and upregulating CCND1 gene expression. Combination
therapy involving ObRb knockdown and tamoxifen treatment may be an alternative
therapeutic option for tamoxifen-resistant breast cancer.
PMID- 25846734
TI - miR-335 inhibits the proliferation and invasion of clear cell renal cell
carcinoma cells through direct suppression of BCL-W.
AB - Increasing evidence has demonstrated that small non-coding microRNAs (miRNAs)
play important roles in cancer development and progression. Recent studies have
shown that microRNA-335 (miR-335) functions as an oncogene or a tumor suppressor
in various human cancer types, but its role in clear cell renal cell carcinoma
(ccRCC) remains poorly understood. In our study, we firstly found that the
expression level of miR-335 was significantly downregulated in ccRCC tissues
versus corresponding non-tumor tissues and the low expression of miR-335 was
significantly associated with lymph node metastasis, larger tumor size, and poor
T stage. Then, we found that overexpression of miR-335 significantly suppressed
the proliferation and invasion of 786-O and CaKi-1 ccRCC cell lines. We
subsequently found that miR-335 could interact with the 3'-untranslated regions
(3'UTR) of B-cell CLL/lymphoma 2 like 2 (BCL-W or BCL2L2) messenger RNA (mRNA)
and repress its expression. In addition, re-expression of BCL-W (without the
3'UTR) could partially abrogate the miR-335-induced 786-O and CaKi-1 ccRCC cell
proliferation and invasion inhibition. Furthermore, we found that expression
patterns of miR-335 were inversely correlated with those of BCL-W mRNA in ccRCC
tissues. Taken together, these results indicate that miR-335 acts as a novel
tumor suppressor to regulate ccRCC cell proliferation and invasion through
downregulation of BCL-W expression.
PMID- 25846735
TI - Clinical significance of topoisomerase 2A expression and gene change in operable
invasive breast cancer.
AB - This study aims to investigate clinical significance of topoisomerase 2A (TOP2A)
expression and TOP2A gene change in operable invasive breast cancer. This is a
retrospective analysis, which includes 256 patients diagnosed as operable
invasive breast cancer. All postoperational waxed specimens were subjected to
resectioning for staining. Estrogen receptor (ER), progesterone receptor (PR),
human epidermal growth factor receptor 2 (HER-2), KI-67, TOP2A expression, and
TOP2A gene changes were detected by immunohistochemistry (IHC) and fluorescent in
situ hybridization technique (FISH), respectively. Correlation between TOP2A
expression and clinicopathological characteristics was also investigated. Effects
of TOP2A protein or gene changes on survival rate were detected. Results
indicated that 165 were TOP2A positive (64.5 %), and 31 were gene amplification
positive (12.1 %). Positive rate of TOP2A expression showed significant
correlations with ER, KI-67, and HER-2. The difference of 5-year overall survival
(OS) between TOP2A-positive and TOP2A-negative groups did not reach statistical
significance (OS: P = 0.321, 85.9 vs. 79.6 %; disease-free survival [DFS]: P =
0.247, 83.3 vs. 75.3 %). Five-year OS in TOP2A amplification group was 68.8 %,
which is lower than deficiency and control group (P > 0.05). Subgroup analysis
showed no significant differences of OS and DFS either between TOP2A-positive and
TOP2A-negative groups or between TOP2A amplification and control group in
population of patients with HER-2 amplification, triple negative breast cancer,
or hormone-positive breast cancer. In conclusion, positive rate of TOP2A
expression correlates significantly with ER, KI-67, and HER-2. However,
prognostic significance of either TOP2A expression or TOP2A gene changes in
breast cancer and its various subtypes is limited.
PMID- 25846737
TI - Antitumor activity of photodynamic therapy with a chlorin derivative in vitro and
in vivo.
AB - Chlorin derivatives are promising photosensitive agents for photodynamic therapy
(PDT) of tumors. The aim of the current study is to investigate the PDT
therapeutic effects of a novel chlorin-based photosensitizer, meso-tetra[3-(N,N
diethyl)aminomethyl-4-methoxy]phenyl chlorin (TMPC) for gliomas in vitro and in
vivo. Physicochemical characteristics of TMPC were recorded by ultraviolet
visible spectrophotometer and fluorescence spectrometer. The rate of singlet
oxygen generation of TMPC upon photo-excitation was detected by using 1,3
diphenylisobenzofuran (DPBF). The accumulation of TMPC in gliomas U87 MG cells
was measured by fluorescence spectrometer. The efficiency of TMPC-PDT in vitro
was analyzed by MTT assay and clonogenic assay. The biodistribution and clearance
of TMPC were determined by fluorescence measuring. Human gliomas U87 MG tumor
bearing mice model was used to evaluate the antitumor effects of TMPC-PDT. TMPC
shows a singlet oxygen generation rate of 0.05 and displays a characteristic long
wavelength absorption peak at 653 nm (epsilon = 15,400). The accumulation of TMPC
increased with the increase of incubation time. In vitro, PDT using TMPC and
laser showed laser dose- and concentration-dependent cytotoxicity to U87 MG
cells. In U87 MG tumor-bearing mice, TMPC-PDT significantly reduced the growth of
the tumors. Both in vitro and in vivo, TMPC showed little dark toxicity. In vitro
and in vivo studies, it found that TMPC has excellent antitumor activities. It
suggests that TMPC is a potential photosensitizer of photodynamic therapy for
cancer.
PMID- 25846736
TI - Clinical significance and biological roles of TRIM24 in human bladder carcinoma.
AB - Tripartite motif-containing 24 (TRIM24), also known as transcription intermediary
factor 1-alpha (TIF1alpha), is a chromatin-associated protein which as been has
been implicated in carcinogenesis. However, its expression profile and biological
roles in human bladder carcinoma has not been investigated. In this study, we
examined its expression in 95 bladder cancer specimens. We found that TRIM24
expression was upregulated in 39 of 95 (41.1 %) specimens compared with normal
control. TRIM24 overexpression was associated with local invasion and advanced
grade of bladder cancer. In addition, we transfected TRIM24 plasmid into BIU-87
cell line and TRIM24 siRNA into 5637 cell line. Colony formation, CCK-8, and
transwell assay were used to assess its biological roles in bladder cancer cells.
The result showed that TRIM24 could facilitate cancer cell growth and invading
ability. Western blot analysis demonstrated that TRIM24 upregulated cyclin D1,
cyclin E, p-IkappaBalpha, and p-AKT expression, suggesting TRIM24 activates NF
kappaB and AKT pathways. In addition, NF-kappaB inhibitor reversed the effect of
TRIM24 on cyclin D1. In conclusion, TRIM24 is overexpressed in human bladder
cancer and facilitates bladder cancer growth and invasion, possibly through NF
kappaB and AKT signaling pathways.
PMID- 25846738
TI - MicroRNA-9 promotes tumorigenesis and mediates sensitivity to cisplatin in
primary epithelial ovarian cancer cells.
AB - MicroRNAs play critical roles in regulating tumor occurrence and drug sensitivity
in ovarian cancers. This study aimed to investigate the key members of MicroRNAs
(miRNAs) involved in modulating tumor initiation and drug resistance in primary
ovarian cancer cells. An in vitro assay based on tumor clonal formation was
established to evaluate tumorigenicity and cisplatin sensitivity. By performing
real-time polymerase chain reaction, we examined the expression of nine microRNAs
associated with the pathology of ovarian cancers in primary ovarian tumor cells,
which were surgically resected from 46 patients with distinct sensitivity to
platinum-based chemotherapy. MiR-9, miR-145, and miR-429 were expressed
significantly higher in drug-sensitive patients (n = 26) than in drug-resistant
ones (n = 20), while higher miR-26a expression was found in resistant patients (p
< 0.05). In addition, tumor cells from drug sensitive patients were more
tumorigenic than those of drug resistance (p = 0.0013). Cisplatin treatment led
to a sharp decrease of clonal formation of drug-sensitive cells but showed slight
effects on drug resistant cells. Specific anti-miRs were then employed to
downregulate the expression of microRNAs in primary tumor cells. Inhibition of
miR-9 resulted in decreased clonal formation and sensitivity to cisplatin, while
the knockdown of other three microRNAs did not show any influence in
tumorigenesis and drug sensitivity. In conclusion, this study showed that in
primary ovarian tumor cells, high expression of miR-9 was associated with
enhanced tumorigenesis and increased sensitivity of the tumor cells to cisplatin
treatment.
PMID- 25846739
TI - Failure of self-disclosure of deferrable risk behaviors associated with
transfusion-transmissible infections in blood donors.
AB - BACKGROUND: To date, most studies on deferral of blood donors have focused on men
who have sex with men (MSM) and/or injecting drug users. Few have examined
deferrable risk behaviors relating to transfusion-transmissible infections (TTIs)
in general. This study aimed to examine the prevalence of, and factors associated
with, nondisclosure of TTI-related risk behaviors in donors. STUDY DESIGN AND
METHODS: Chinese-speaking donors who had just given blood in Hong Kong were
invited to self-complete an anonymous questionnaire. Practices of one or more of
seven deferrable risk behaviors associated with TTI were inquired. Factors
associated with noncompliance with self-disclosure were evaluated by logistic
regression. RESULTS: Over a 4-week study period in 2012, a total of 1143 donors
were recruited. Overall, 0.2% gave a history of drug injection, 1.7% had had sex
with sex worker(s), and 0.3% had had sex with a human immunodeficiency virus
infected partner, while none had been paid for sex. Some 1.5% of male donors
reported having same-sex behaviors. Factors associated with noncompliance were
male gender (odds ratio [OR] 31.1; 95% confidence interval [CI], 3.7-263.6),
having multiple sex partners (OR, 89.7; 95% CI, 28.7-279.9), and previous history
of temporary deferral (OR, 11.4; 95% CI, 2.5-53.3). If suspected noncompliance
was included, the overall prevalence of nondisclosure of deferrable behaviors
could be high at 6.5%. CONCLUSION: Albeit uncommon, some donors fail to provide
accurate answers to predonation screening questions and are not deferred
appropriately. There is room for improvement to make deferral policy acceptable
and understandable, so as to minimize the risk of TTI. Efforts are also needed to
tackle the paucity of data on noncompliance of non-MSM donors.
PMID- 25846740
TI - Single-incision laparoscopic surgery through the umbilicus is associated with a
higher incidence of trocar-site hernia than conventional laparoscopy: a meta
analysis of randomized controlled trials.
AB - BACKGROUND: Single-incision laparoscopic surgery has been developed with the
objective to reduce surgical trauma, decrease associated surgical stress and to
improve cosmetic outcome. However, concerns have been raised regarding the risk
of trocar-site hernia following this approach. Previous meta-analyses have
suggested a trend toward higher hernia rates, but have failed to demonstrate a
significant difference between single-incision and conventional laparoscopic
surgery. METHOD: Medline, AMED, CINAHL and CENTRAL were searched up to May 2014.
Randomized controlled trials comparing single-incision and conventional
laparoscopic surgery were considered for inclusion. Studies with patients aged
less than 18 years and those reporting on robotic surgery were disregarded.
Pooled odds ratios with 95% confidence intervals were calculated to measure the
comparative risk of trocar-site hernia following single-incision and conventional
laparoscopic surgery. RESULTS: Nineteen randomized trials encompassing 1705
patients were included. Trocar-site hernia occurred in 2.2% of patients in the
single-incision group and in 0.7% of patients in the conventional laparoscopic
surgery group (odds ratio 2.26, 95% confidence interval 1.00-5.08, p = 0.05).
Sensitivity analysis of quality randomized trials validated the outcome estimates
of the primary analysis. There was no heterogeneity among studies (I2 = 0%) and
no evidence of publication bias. CONCLUSION: Single-incision laparoscopic surgery
involving entry into the peritoneal cavity through the umbilicus is associated
with a slightly higher risk of trocar-site hernia than conventional laparoscopy.
Its effect on long-term morbidity and quality of life is a matter for further
investigation.
PMID- 25846741
TI - Next steps for birth defects research and prevention: The birth defects study to
evaluate pregnancy exposures (BD-STEPS).
AB - BACKGROUND: The Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS) is
a population-based, multi-Center case-control study of modifiable risk factors
for selected birth defects in the United States. BD-STEPS is the second major
research effort of the Centers for Birth Defects Research and Prevention, which
extends and expands the initial research effort, the National Birth Defects
Prevention Study (NBDPS). METHODS: BD-STEPS focuses on 17 categories of
structural birth defects selected based on severity, prevalence, consistent
ascertainment, and previous findings that warrant additional research. Cases are
identified through existing birth defects surveillance programs; controls are
from vital records or birth hospital logs from the same catchment area. BD-STEPS
uses a standardized computer-assisted telephone interview to collect information
from case and control mothers on topics including demographics, health
conditions, and medication use. Following the maternal interview, selected
Centers request permission to sample residual newborn screening blood spots from
state repositories for genetic analyses. New components planned for BD-STEPS
include linkages with external datasets and use of online questionnaires to
collect in-depth information on selected exposures. RESULTS: BD-STEPS extends
NBDPS by continuing to collect data on many exposures that were assessed in
NBDPS, allowing data from both studies to be combined and providing an
unprecedented sample size to analyze rare exposures. BD-STEPS expands upon NBDPS
by collecting more detailed information on existing exposures as well as new
exposures. CONCLUSION: The goal of BD-STEPS is to provide women and healthcare
providers with information they need to make decisions to promote the healthiest
pregnancy possible.
PMID- 25846742
TI - vapA (A-layer) typing differentiates Aeromonas salmonicida subspecies and
identifies a number of previously undescribed subtypes.
AB - Sequence variation in a region of the virulence array protein gene (vapA; A
layer) was assessed in 333 ('typical' and 'atypical') isolates of the fish
pathogenic bacterium Aeromonas salmonicida. Resulting similarity dendrograms
revealed extensive heterogeneity, with nearly all isolates belonging to either of
14 distinct clusters or A-layer types. All acknowledged A. salmonicida subspecies
(except ssp. pectinolytica, from which no vapA sequence could be obtained) were
clearly separated, and notably, all isolates phenotypically identified as ssp.
salmonicida formed a distinct and exclusive A-layer type. Additionally, an array
of un-subspeciated atypical strains formed several equally prominent clusters,
demonstrating that the concept of typical/atypical A. salmonicida is
inappropriate for describing the high degree of diversity evidently occurring
outside ssp. salmonicida. Most representatives assessed in this study were
clinical isolates of spatiotemporally diverse origins, and were derived from a
variety of hosts. We observed that from several fish species or families,
isolates predominantly belonged to certain A-layer types, possibly indicating a
need for host-/A-layer type-specific A. salmonicida vaccines. All in all, A-layer
typing shows promise as an inexpensive and rapid means of unambiguously
distinguishing clinically relevant A. salmonicida subspecies, as well as
presently un-subspeciated atypical strains.
PMID- 25846743
TI - Clinical implications of basic science discoveries: nociceptive neurons as
targets to control immunity--potential relevance for transplantation.
AB - Increasing evidence indicates the existence of a complex cross-regulation between
the most important biosensors of the human body: The immune and nervous systems.
Cytokines control body temperature and trigger autoimmune disorders in the
central nervous system, whereas neuropeptides released in peripheral tissues and
lymphoid organs modulate inflammatory (innate) and adaptive immune responses.
Surprisingly, the effects of nerve fibers and the antidromic release of its pro
inflammatory neuropeptides on the leukocytes of the immune system that mediate
graft rejection are practically unknown. In the transplantation field, such area
of research remains practically unexplored. A recent study by Riol-Blanco et al
has revealed new details on how nociceptive nerves regulate the pro-inflammatory
function of leukocytes in peripheral tissues. Although the mechanism(s) by which
neuroinflammation affects the immune response against the allograft remains
unknown, recent data suggest that this new area of research is worth exploring
for potential development of novel complementary therapies for
prevention/treatment of graft rejection.
PMID- 25846744
TI - Cytotoxic effects of chemokine receptor 4 inhibition by AMD3100 in biliary tract
cancer cells: Potential drug synergism with gemcitabine.
AB - Biliary tract cancer (BTC) remains one of the most life-threatening types of
cancer due to the lack of efficient therapies. Advanced tumour stages at the
point of diagnosis and high chemoresistance are two of the predominant reasons
for a 5-year survival rate of only ~5%. The present study investigated the effect
of the chemokine receptor 4 (CXCR4) inhibitor AMD3100 (Plerixafor), alone and in
combination with standard gemcitabine chemotherapy, on the proliferation of BTC
cells. The expression of CXCR4 was analysed by reverse transcription-quantitative
polymerase chain reaction in eight heterogeneously differentiated BTC cell lines.
The effects of treatment with the CXCR4 antagonist, AMD3100, on cell viability
and anchorage-independent growth, and the possible synergistic cytotoxic effects
of AMD3100 with standard chemotherapeutics were assessed. The expression of CXCR4
was observed to a variable extent in all eight BTC cell lines, with SkChA-1 cells
exhibiting the highest expression levels. Treatment with AMD3100 led to a
marginal decrease in cell viability in the cell lines, with the exception of the
CCSW-1 cells, and a significant reduction in the GBC, MzChA-1, SkChA.-1 and TFK-1
cell lines. The combined treatment of the SkChA-1 cells with varying
concentrations of AMD3100 and standard gemcitabine chemotherapy revealed a more
marked overall cytotoxicity, indicating a potential synergistic effect. In
addition, AMD3100 significantly reduced anchorage-independent growth in the SkChA
1 cells. Overall, the results of the present study suggest that the inhibition of
CXCR4 by AMD3100, in combination with gemcitabine, may be a suitable strategy for
the future therapy of BTC.
PMID- 25846745
TI - Systematic review of experimental studies on intestinal anastomosis.
AB - BACKGROUND: The contribution of animal research to a reduction in clinical
intestinal anastomotic leakage is unknown, despite numerous experimental studies.
In view of the current societal call to replace, reduce and refine animal
experiments, this study examined the quality of animal research related to
anastomotic healing and leakage. METHODS: Animal studies on intestinal
anastomotic healing were retrieved systematically from PubMed and Embase. Study
objective, conclusion and animal model were recorded. Reporting quality and
internal validity (reporting of randomization and blinding) were assessed.
RESULTS: A total of 1342 studies were identified, with a rising publication rate.
The objectives of most studies were therapeutic interventions (64.8 per cent) and
identification of risk factors (27.5 per cent). Of 350 articles studying
experimental therapies, 298 (85.1 per cent) reported a positive effect on
anastomotic healing. On average, 44.7 per cent of relevant study characteristics
were not reported, in particular details on anastomotic complications (31.6 per
cent), use of antibiotics (75.7 per cent), sterile surgery (83.4 per cent) and
postoperative analgesia (91.4 per cent). The proportion of studies with
randomization, blinding of surgery and blinding of primary outcome assessment has
increased in the past two decades but remains insufficient, being included in
only 62.4, 4.9 and 8.5 per cent of publications respectively. Animal models
varied widely in terms of species, method to compromise healing, intestinal
segment and outcome measures used. CONCLUSION: Animal research on anastomotic
leakage is of poor quality and still increasing, contrary to societal aims.
Reporting and study quality must improve if results are to impact on patients.
PMID- 25846747
TI - Hand therapy following elbow release for passive elbow flexion and long head of
the triceps transfer for active elbow flexion in children with amyoplasia.
AB - Children born with the Amyoplasia form of arthrogryposis multiplex congenita
(AMC) who lack elbow flexor muscles and have elbow extension contractures usually
require assistance in performing ADL's that require reaching their hand to their
face, head, and upper body. For tasks involving the UE, the elbow is the key to
functional independence. Children born with Amyoplasia may benefit from selective
surgeries to enhance functional independence and improve quality of life. Home
therapy and splinting following these surgeries is an important part of gaining
motion and improving function. This abstract will review the rehab and splinting
following an elbow release to gain passive elbow flexion, and a long head of the
triceps transfer for active elbow flexion in children with Amyoplasia.
PMID- 25846746
TI - Adolescent girls' neural response to reward mediates the relation between
childhood financial disadvantage and depression.
AB - BACKGROUND: Children who experience socioeconomic disadvantage are at heightened
risk for developing depression; however, little is known about neurobiological
mechanisms underlying this association. Low socioeconomic status (SES) during
childhood may confer risk for depression through its stress-related effects on
the neural circuitry associated with processing monetary rewards. METHODS: In a
prospective study, we examined the relationships among the number of years of
household receipt of public assistance from age 5-16 years, neural activation
during monetary reward anticipation and receipt at age 16, and depression
symptoms at age 16 in 123 girls. RESULTS: Number of years of household receipt of
public assistance was positively associated with heightened response in the
medial prefrontal cortex during reward anticipation, and this heightened neural
response mediated the relationship between socioeconomic disadvantage and current
depression symptoms, controlling for past depression. CONCLUSIONS: Chronic
exposure to socioeconomic disadvantage in childhood may alter neural circuitry
involved in reward anticipation in adolescence, which in turn may confer risk for
depression.
PMID- 25846748
TI - The conservation profile of a protein bears the imprint of the molecule that is
evolutionarily coupled to the protein.
AB - The conservation profile of a protein is a curve of the conservation levels of
amino acids along the sequence. Biologists are usually more interested in
individual points on the curve (namely, the conserved amino acids) than the
overall shape of the curve. Here, we show that the conservation curves of
proteins bear the imprints of molecules that are evolutionarily coupled to the
proteins. Our method is based on recent studies that a sequence conservation
profile is quantitatively linked to its structural packing profile. We find that
the conservation profiles of nucleic acid (NA) binding proteins are better
correlated with the packing profiles of the protein-NA complexes than those of
the proteins alone. This indicates that a nucleic acid binding protein evolves to
accommodate the nucleic acid in such a way that the residues involved in binding
have their conservation levels closely coupled with the specific nucleotides.
PMID- 25846749
TI - TBBPA induces developmental toxicity, oxidative stress, and apoptosis in embryos
and zebrafish larvae (Danio rerio).
AB - Tetrabromobisphenol A (TBBPA) is currently one of the most frequently used
brominated flame retardants and can be considered as a high production volume
chemical. In this study, zebrafish embryos and larvae served as a biological
model to evaluate TBBPA-induced developmental toxicity, oxidative stress, oxidant
associated gene expression, and cell apoptosis. Abnormalities, including
hyperemia and pericardial edema, were induced in zebrafish larvae. The results
showed that toxicity endpoints such as hatching rate, survival rate, malformation
rate, and growth rate had a significant dose-response relationship with TBBPA.
Further studies revealed that TBBPA did not alter the enzyme activities of
Copper/Zinc Superoxide dismutase (Cu/Zn-SOD), catalase (CAT), and
glutathioneperoxidase (GPx) at 0.10 mg/L, but decreased activities following
exposure to 0.40, 0.70, and 1.00 mg/L. Despite the significantly decreased gene
expression of Cu/Zn-SOD, CAT, and GPx1a in the 1.00 mg/L treatment group, other
treatments (0.10, 0.40, 0.70 mg/L) did not alter gene expression. Moreover,
Acridine orange staining results showed that apoptotic cells mainly accumulated
in the brain, heart, and tail, indicating possible TBBPA-induced brain, cardiac,
and blood circulation system impairment in zebrafish embryos and larvae.
Histological analysis also showed evidence of obvious heart impairment in TBBPA
treated groups. This study provides new evidence on the developmental toxicity,
oxidative stress, and apoptosis of embryos and zebrafish larvae, which is
important for the evaluation of environmental toxicity and chemical risk. (c)
2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1241-1249, 2016.
PMID- 25846750
TI - Role of PO4 tetrahedron in LiFePO4 and FePO4 system.
AB - Using high resolution transmission electron microscopy with image simulation and
Fourier analysis, the Li1- x FePO4 (x < 0.01), Li1- x FePO4 (x ~ 0.5), and FePO4
particles, prepared by charging or discharging the 053048 electrochemical cells
(thickness: 5 mm, width: 30 mm, height: 48 mm) and dismantled inside an Ar-filled
dry box, were investigated. The high resolution images reveal: (1) the solid
solution of Li1- x FePO4 (x < 0.01) contains some missing Li ions leading PO4
group distorted around M1 tunnel of the unit cell; (2) the texture of the
particles of Li1- x FePO4 (x ~0.5) has homogeneously distributed compositional
domains of LiFePO4 and FePO4 resulting from spinodal decomposition which promote
Li ion easily getting into the particle due to uphill diffusion, (3) the
particles of FePO4 formed in charging have heavily distorted lattice and contain
some isolated LiFePO4 , (4) interface between LiFePO4 and FePO4 and between
amorphous and crystal region provides the lattice distortion of small polarons.
PMID- 25846751
TI - Re: Steven Joniau, Alberto Briganti, Paolo Gontero, et al. Stratification of High
risk Prostate Cancer into Prognostic Categories: A European Multi-institutional
Study. Eur Urol 2015;67:157-64.
PMID- 25846752
TI - Aspirin counteracts cancer stem cell features, desmoplasia and gemcitabine
resistance in pancreatic cancer.
AB - Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor
prognosis. An inflammatory microenvironment triggers the pronounced desmoplasia,
the selection of cancer stem-like cells (CSCs) and therapy resistance. The anti
inflammatory drug aspirin is suggested to lower the risk for PDA and to improve
the treatment, although available results are conflicting and the effect of
aspirin to CSC characteristics and desmoplasia in PDA has not yet been
investigated. We characterized the influence of aspirin on CSC features, stromal
reactions and gemcitabine resistance. Four established and 3 primary PDA cell
lines, non-malignant cells, 3 patient tumor-derived CSC-enriched spheroidal
cultures and tissues from patients who did or did not receive aspirin before
surgery were analyzed using MTT assays, flow cytometry, colony and spheroid
formation assays, Western blot analysis, antibody protein arrays, electrophoretic
mobility shift assays (EMSAs), immunohistochemistry and in vivo
xenotransplantation. Aspirin significantly induced apoptosis and reduced the
viability, self-renewal potential, and expression of proteins involved in
inflammation and stem cell signaling. Aspirin also reduced the growth and
invasion of tumors in vivo, and it significantly prolonged the survival of mice
with orthotopic pancreatic xenografts in combination with gemcitabine. This was
associated with a decreased expression of markers for progression, inflammation
and desmoplasia. These findings were confirmed in tissue samples obtained from
patients who had or had not taken aspirin before surgery. Importantly, aspirin
sensitized cells that were resistant to gemcitabine and thereby enhanced the
therapeutic efficacy. Aspirin showed no obvious toxic effects on normal cells,
chick embryos or mice. These results highlight aspirin as an effective,
inexpensive and well-tolerated co-treatment to target inflammation, desmoplasia
and CSC features PDA.
PMID- 25846754
TI - Genomics of adaptation to host-plants in herbivorous insects.
AB - Herbivorous insects represent the most species-rich lineages of metazoans. The
high rate of diversification in herbivorous insects is thought to result from
their specialization to distinct host-plants, which creates conditions favorable
for the build-up of reproductive isolation and speciation. These conditions rely
on constraints against the optimal use of a wide range of plant species, as each
must constitute a viable food resource, oviposition site and mating site for an
insect. Utilization of plants involves many essential traits of herbivorous
insects, as they locate and select their hosts, overcome their defenses and
acquire nutrients while avoiding intoxication. Although advances in understanding
insect-plant molecular interactions have been limited by the complexity of insect
traits involved in host use and the lack of genomic resources and functional
tools, recent studies at the molecular level, combined with large-scale genomics
studies at population and species levels, are revealing the genetic underpinning
of plant specialization and adaptive divergence in non-model insect herbivores.
Here, we review the recent advances in the genomics of plant adaptation in
hemipterans and lepidopterans, two major insect orders, each of which includes a
large number of crop pests. We focus on how genomics and post-genomics have
improved our understanding of the mechanisms involved in insect-plant
interactions by reviewing recent molecular discoveries in sensing, feeding,
digesting and detoxifying strategies. We also present the outcomes of large-scale
genomics approaches aimed at identifying loci potentially involved in plant
adaptation in these insects.
PMID- 25846753
TI - Targeting Toll-like receptor 2 inhibits growth of head and neck squamous cell
carcinoma.
AB - Infection-driven inflammation has been proposed to be involved in the
tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Oral HNSCC is
often colonized with microbes such as gram-positive bacteria and yeast, where
ligands derived from their wall components have been shown to specifically bind
to Toll-like receptor 2 (TLR2). Although TLR2 has been described to be expressed
in oral HNSCC, its function has not been well characterized. Here, we show the
expression of TLR2 in both HNSCC cell lines and primary patient-derived HNSCC
xenograft tumors. Activation of TLR2 with a yeast-derived ligand of TLR2,
zymosan, promoted organoid formation in an ex vivo model of tumor growth, while
blockade with anti-TLR2 antibodies inhibited organoid formation. Zymosan also
induced phosphorylation of ERK and the p65 subunit of NF-kappaB, which was
inhibited in the presence of anti-TLR2 antibodies, indicating that this receptor
is functional in HNSCC and that the signaling through these pathways is intact.
TLR2 blockade also inhibited growth of human xenografted tumors in
immunodeficient mice. In summary, our data show that TLR2 is a functional
receptor expressed in human HNSCC that plays a direct pro-tumorigenic role, and
that it can be therapeutically targeted with blocking antibodies to reduce tumor
growth.
PMID- 25846756
TI - Patterns of Dating Violence Perpetration and Victimization in U.S. Young Adult
Males and Females.
AB - Dating violence (DV) is frequently reported by young adults in intimate
relationships in the United States, but little is known about patterns of DV
perpetration and victimization. In this study, we examined sexual and physical
violence perpetration and victimization reported by young adults to determine how
the violence patterns differ by sex and race/ethnicity. Data from non-Hispanic
White, non-Hispanic Black, and Hispanic participants in Wave 3 of the National
Longitudinal Study of Adolescent to Adult Health were analyzed. DV was assessed
using responses to four questions focused on perpetration and four questions
focused on victimization. The information on DV was taken from the most violent
relationship reported by participants prior to Wave 3. Latent class analysis was
first conducted separately by sex, adjusting for age, race/ethnicity, and
financial stress, then by race/ethnicity, adjusting for age and financial stress.
Relative model fit was established by comparing Bayesian Information Criteria
(BIC), adjusted BIC, entropy, interpretability of latent classes, and certainty
of latent class assignment for covariate-adjusted models. The results indicate
that patterns of violence differed by sex and for females, by race/ethnicity. A
three-class model was the best fit for males. For females, separate four-class
models were parsimonious for White, Black, and Hispanic females. Financial stress
was a significant predictor of violence classification for males and females and
age predicted membership in White and Black female models. Variations in DV
patterns by sex and race/ethnicity suggest the need for a more nuanced
understanding of differences in DV.
PMID- 25846757
TI - Examining Intimate Partner Violence and Health Factors Among Rural Appalachian
Pregnant Women.
AB - Among pregnant women, intimate partner violence (IPV) is recognized as a critical
risk factor in adverse health outcomes for the mother and newborn alike. This
pilot study examined IPV and health for rural Appalachian pregnant women, a
particularly vulnerable high-risk and high-needs group. Participants were 77
rural, Appalachian pregnant women entering a hospital-based inpatient
detoxification unit primarily for Opiate Dependence. Study participants gave
informed consent to a face-to-face interview and secondary data abstraction from
hospital medical records. IPV was measured via questions from the National
Violence Against Women Survey, the Revised Conflict Tactics Scale (CTS2), and the
Psychological Maltreatment of Women Inventory (PMWI). The majority of the sample
reported lifetime psychological (89.6%) and physical (64.9%) violence. A little
over three fourths (75.3%) experienced IPV in the past year. Furthermore, over
one third (39.0%) experienced stalking, physical, or sexual violence in the past
year. Most participants (71.4%) experienced psychological abuse in the past year.
IPV experiences, in conjunction with pervasive substance use, mental and physical
health problems, and poverty present in rural Appalachia, culminate in a
particularly high-risk and high-needs group of pregnant women. These women
present unique opportunities and challenges for prevention, intervention, and
treatment.
PMID- 25846755
TI - Nuclear processes associated with plant immunity and pathogen susceptibility.
AB - Plants are sessile organisms that have evolved exquisite and sophisticated
mechanisms to adapt to their biotic and abiotic environment. Plants deploy
receptors and vast signalling networks to detect, transmit and respond to a given
biotic threat by inducing properly dosed defence responses. Genetic analyses and,
more recently, next-generation -omics approaches have allowed unprecedented
insights into the mechanisms that drive immunity. Similarly, functional genomics
and the emergence of pathogen genomes have allowed reciprocal studies on the
mechanisms governing pathogen virulence and host susceptibility, collectively
allowing more comprehensive views on the processes that govern disease and
resistance. Among others, the identification of secreted pathogen molecules
(effectors) that modify immunity-associated processes has changed the plant
microbe interactions conceptual landscape. Effectors are now considered both
important factors facilitating disease and novel probes, suited to study immunity
in plants. In this review, we will describe the various mechanisms and processes
that take place in the nucleus and help regulate immune responses in plants.
Based on the premise that any process required for immunity could be targeted by
pathogen effectors, we highlight and describe a number of functional assays that
should help determine effector functions and their impact on immune-related
processes. The identification of new effector functions that modify nuclear
processes will help dissect nuclear signalling further and assist us in our bid
to bolster immunity in crop plants.
PMID- 25846758
TI - Understanding Disparities in Service Seeking Following Forcible Versus Drug- or
Alcohol-Facilitated/Incapacitated Rape.
AB - Victims of drug- or alcohol-facilitated/incapacitated rape (DAFR/IR) are
substantially less likely to seek medical, rape crisis, or police services
compared with victims of forcible rape (FR); however, reasons for these
disparities are poorly understood. The current study examined explanatory
mechanisms in the pathway from rape type (FR vs. DAFR/IR) to disparities in post
rape service seeking (medical, rape crisis, criminal justice). Participants were
445 adult women from a nationally representative household probability sample who
had experienced FR, DAFR/IR, or both since age 14. Personal characteristics (age,
race, income, prior rape history), rape characteristics (fear, injury, loss of
consciousness), and post-rape acknowledgment, medical concerns, and service
seeking were collected. An indirect effects model using bootstrapped standard
errors was estimated to examine pathways from rape type to service seeking.
DAFR/IR-only victims were less likely to seek services compared with FR victims
despite similar post-rape medical concerns. FR victims were more likely to report
fear during the rape and a prior rape history, and to acknowledge the incident as
rape; each of these characteristics was positively associated with service
seeking. However, only prior rape history and acknowledgment served as indirect
paths to service seeking; acknowledgment was the strongest predictor of service
seeking. Diminished acknowledgment of the incident as rape may be especially
important to explaining why DAFR/IR victims are less likely than FR victims to
seek services. Public service campaigns designed to increase awareness of rape
definitions, particularly around DAFR/IR, are important to reducing disparities
in rape-related service seeking.
PMID- 25846759
TI - Age, Marital Status, and Risk of Sexual Victimization: Similarities and
Differences Across Victim-Offender Relationships.
AB - By now, age and marital status are well-established correlates of criminal
victimization, including adult women's sexual victimization. National crime
statistics, as well as a large body of scholarly literature, have specified that
younger women and unmarried women are at comparatively higher risk of sexual
victimization than older women and married women. Few studies, however, have
examined the relationship between age, marital status, and risk of victimization
across diverse situational contexts of sexual victimization. The current study
used data from the National Crime Victimization Survey (NCVS) to examine whether
the relationship between age, marital status, and risk of sexual victimization
varied across victimization experiences involving three victim-offender
relationships: stranger, acquaintance, and intimate partner. Results indicate
both similarities and differences in the relationship between age, marital
status, and risk of victimization across these three situational contexts of
victimization. As expected, age was a significant predictor of victimization in
all models; however, younger women's increased risk of victimization was far more
pronounced for acquaintance and intimate partner victimization experiences as
compared with stranger experiences. Also, consistent with prior research,
unmarried women were at higher risk of victimization in all models; however,
within unmarried status categories, separated women were at highest risk of both
intimate partner and acquaintance victimization experiences as compared with
never married or divorced women.
PMID- 25846760
TI - The Use of Anthracyclines for Therapy of CNS Tumors.
AB - Despite being long lived, anthracyclines remain the "evergreen" drugs in clinical
practice of oncology, showing a potent effect in inhibiting cell growth in many
types of tumors, including brain neoplasms. Unfortunately, they suffer from a
poor penetration into the brain when intravenously administered due to multidrug
resistance mechanism, which hampers their delivery across the blood brain
barrier. In this paper, we summarize the current literature on the role of
anthracyclines in cancer therapy and highlight recent efforts on 1) development
of tumor cell resistance to anthracyclines and 2) the new approaches to brain
drug delivery across the blood brain barrier.
PMID- 25846761
TI - A Novel Approach to Inhibit Heat Shock Response as Anticancer Strategy by
Coumarine Compounds Containing Thiazole Skeleton.
AB - Inhibition of the Hsp90 function is an essential therapeutic approach and several
inhibitors were designed as anti-cancer agents. These inhibitors are ATPases and
they aim to deregulate Hsp90 folding function. ATPase proteins are common in
human metabolism but they form nonspecific targets. Hsp90 functions as dimer with
coordinating chaperones. Heat Shock Organizing Protein (Hop) forms a bridge
between Hsp90 and Hsp70-Hsp40 complex to form Hsp90-Hsp70 coordination.
Perturbing conformational changes of these Hsp proteins, dimer formation, and
protein-protein interactions inhibit Hsp90 substrate protein folding function.
This approach does not target all ATPase proteins but targets Hsp90 function
solely. For this purpose, we designed compounds to block Hsp90 function.
Moreover, molecular docking studies as well as competition analysis of the
compounds were performed with Hsp90. Novel thiazolyl coumarine compounds were
determined as valuable C-terminal Hsp90 inhibitors and provide promising
templates for the drug design. Anticancer activities of these novel compounds
were tested by employing human colon (DLD-1) and liver cancer (HepG2) cell lines.
Thiazolyl coumarine compounds are found to be significant and useful for the
treatment of human colon and liver cancer as evidenced by in vitro and in silico
results.
PMID- 25846762
TI - Dichloroacetate stimulates changes in the mitochondrial network morphology via
partial mitophagy in human SH-SY5Y neuroblastoma cells.
AB - Dichloroacetate (DCA) is beneficial in cancer therapy because it induces
apoptosis and decreases cancer growth in vitro and in vivo without affecting non
cancer cells. DCA stimulates the activity of the enzyme pyruvate dehydrogenase by
inhibiting pyruvate dehydrogenase kinase. Consequently, DCA promotes oxidative
phosphorylation after glycolysis. Therefore, DCA produces changes in energy
metabolism that could affect the mitochondrial network and mitophagy. This
investigation determined the effects of DCA treatment on mitophagy in human
neuroblastoma SH-SY5Y cells. SH-SY5Y cells were cultured and distributed into 3
groups: control, NH4Cl and chloroquine. Each group was treated with DCA at 0, 5,
30 and 60 mM for 16 h. Samples were analyzed for cell viability, mtDNA copy
number, mitochondrial network morphology and expression of key proteins involved
in mitochondrial dynamics, such as LC3b, FIS1, OPA1, PARKIN and PINK1. In all
groups, DCA caused a decrease in cell viability, an induction of autophagy in a
dose-dependent manner and a decrease in Tim23, FIS1 and PARKIN protein
expression, leading to profound morphological changes in the mitochondrial
network resulting in shorter and more fragmented filaments. However, TFAM protein
levels remained unchanged. Similarly, the mitochondrial copy number was not
significantly different among the treatment groups. In conclusion, DCA induces
mitophagy and remodeling of the mitochondrial network. In this remodeling, DCA
induces a decrease in the expression of key proteins involved in protein
degradation and mitochondrial dynamics but does not significantly affect the
mtDNA density. Blocking late phase autophagy increases the effects of DCA,
suggesting that autophagy protects the cell, at least partially, against DCA.
PMID- 25846763
TI - Configurable Nanosized Metal Oxide Oligomers via Precise "Click" Coupling Control
of Hybrid Polyoxometalates.
AB - Polyoxometalates (POMs) are discrete clusters of redox-active metal oxides, many
of which can be linked to organic moieties. Here, we show how it is possible to
link Mn Anderson POMs to terminal alkyne and azide groups and develop appropriate
conditions for their Cu-catalyzed alkyne-azide cycloaddition (or "click"
reaction). These coupling reactions are then used to link the clusters together,
forming monodisperse linear Mn Anderson oligomers, here with examples ranging in
size from two to five clusters. These oligomers are built up sequentially using a
combination of mono- and difunctionalized clusters, giving an unprecedented level
of control over the size and structure of the resulting hybrid POMs. This new
synthetic methodology therefore opens the way for the synthesis of metal oxide
hybrid oligomers and polymers by coupling control, minimizing side products,
producing nanosized molecular hybrid organic-inorganic oxides ca. 4-9 nm in size,
with molecular weights ranging 2-10 kDa.
PMID- 25846764
TI - Frequency of renal artery stenosis after renal denervation in patients with
resistant arterial hypertension.
AB - Catheter-based ablation of nerves in the adventitia of renal arteries (renal
artery denervation [RAD]) using radiofrequency energy can reduce blood pressure
(BP) in patients with resistant arterial hypertension (RAH). Occurrence of renal
artery stenosis after RAD is still an important concern. We systematically
investigated the renal artery anatomy using magnetic resonance imaging (MRI) or
computed tomography (CT) angiography in a consecutive series of patients 6 months
after RAD. Patients with RAH were treated by RAD after exclusion of secondary
causes of hypertension. RAH was defined by a mean systolic office BP >160 mm Hg.
Renal artery imaging was performed 6 months after RAD by MRI angiography. In case
of any contraindication for MRI, a CT angiography was performed. The primary end
point was the incidence of significant renal artery stenosis (>=70% lumen
diameter reduction). RAD was performed in 76 patients, and evaluation of renal
artery anatomy by MRI (n = 66; 87%) or CT angiography (n = 10; 13%) was performed
in all patients 6 months after RAD. We found no renal artery stenosis but 2 cases
of new nonsignificant stenosis (50% TO 69% lumen diameter reduction). In
responders, mean systolic office BP reduction was -30 mm Hg (p <0.001) and mean
systolic 24-hour BP reduction was -18 mm Hg (p <0.001). In conclusion, the
incidence of significant renal artery stenosis 6 months after RAD seems to be
very low. However, late-onset development of nonsignificant renal artery
narrowing cannot be excluded in some patients and should be anticipated in the
case of RAH relapse or worsening of renal function after successful RAD.
PMID- 25846765
TI - Comparison of aortic annulus size by transesophageal echocardiography and
computed tomography angiography with direct surgical measurement.
AB - This study sought to compare the accuracy of 2-dimensional transesophageal
echocardiography (TEE) and computed tomography angiography (CTA) for noninvasive
aortic annular sizing as required for transcatheter aortic valve implantation
(TAVI). Direct intraoperative (OR) sizing is the gold standard for aortic annular
measurement in surgical aortic valve replacement. Unlike surgical aortic valve
replacement, TAVI requires noninvasive assessment of aortic annular dimensions
for determining the size of prosthesis to be implanted and controversy exists
regarding the best imaging technique for TAVI sizing. Preoperative CTA and OR TEE
images of the aortic annulus in 227 patients who underwent proximal aortic
surgery with OR annular sizing at the Duke University Medical Center were
reviewed. Both imaging techniques were compared with direct OR measurements of
aortic annulus diameter using metric sizers as the gold standard. CTA
overestimated aortic annulus diameter in 72.2% of cases, with 46.3% >1 TAVI valve
size (>3 mm) overestimations, whereas TEE underestimated aortic annulus diameter
in 51.1% of cases, with 16.7% >1 valve-size underestimations. Combining both
techniques improved the estimation of aortic annular size. In conclusion, there
are limitations to current imaging techniques for noninvasive determination of
aortic annular dimensions compared with direct OR sizing. Undersizing by TEE and
oversizing by CTA are common and may be related to differences in methods for
sizing an elliptical structure. Combining measurements from both techniques would
decrease the false exclusion rate for TAVI eligibility because of size mismatch.
PMID- 25846766
TI - Effects of the Mueller maneuver on functional mitral regurgitation and
implications for obstructive sleep apnea.
AB - Obstructive sleep apnea is prevalent and adversely affects cardiovascular health.
However, little is known of the acute effects of an obstructive apnea on
cardiovascular physiology. We hypothesized that pre-existing functional mitral
regurgitation (MR) would worsen during performance of a Mueller maneuver (MM)
used to simulate an obstructive apnea; 15 subjects with an ejection fraction
<=35% and pre-existing functional MR were studied with Doppler echocardiography.
The radius of the proximal flow convergence was used as a measure of mitral
regurgitant flow. Measurements were made at baseline, during the MM, and post-MM.
Areas of all 4 chambers were also measured at these time points, both in systole
and diastole. Mean flow convergence radius for the group decreased significantly
during the transition from the late-MM to post-MM (0.65 -> 0.57 mm, p = 0.001),
implying increased MR during the MM. In addition, in 3 subjects, duration of MR
increased during the MM. Right atrial (RA) areas, both systolic and diastolic,
increased during the maneuver, whereas RA fractional area change decreased,
indicating reduced RA emptying. Left ventricular emptying decreased early in the
maneuver, probably because of the increased afterload burden, and then recovered.
In conclusion, high negative intrathoracic pressure produces changes that,
repeated hundreds of times per night in patients with obstructive sleep apnea,
have the potential to worsen heart failure and predispose affected subjects to
atrial fibrillation.
PMID- 25846767
TI - Contemporary Use of Ticagrelor in Interventional Practice (from Blue Cross Blue
Shield of Michigan Cardiovascular Consortium).
AB - Ticagrelor has greater antiplatelet activity than clopidogrel and is approved for
use in patients with acute coronary syndrome (ACS). There are limited data on use
of ticagrelor in real-world practice. We assessed ticagrelor use in 64,600
patients who underwent percutaneous coronary intervention from January 2012 to
March 2014 at 47 Michigan hospitals in the Blue Cross Blue Shield of Michigan
Cardiovascular Consortium. Preprocedural risk of major adverse events was
estimated with Blue Cross Blue Shield of Michigan Cardiovascular Consortium risk
prediction models. The proportion of patients receiving clopidogrel, prasugrel,
and ticagrelor was 72% (n = 46,864), 20% (n = 12,596), and 8% (n = 5,140),
respectively, using ticagrelor increasing over time. Ticagrelor was used at 45
hospitals, ranging from 0.5% to 64.9% of discharges. Patients receiving
ticagrelor were older (63.6 vs 59.4), more often women (32.9% vs 26.7%), and were
more likely to present with ST-segment elevation myocardial infarction (24.4% vs
18.8%), cardiogenic shock within 24 hours (1.3% vs 0.9%), and anginal class IV
(47.8% vs 43.0%) (p <0.05). Compared with prasugrel, ticagrelor was prescribed in
patients with a higher predicted risk of percutaneous coronary intervention
complications: contrast nephropathy (2.5% vs 1.6%), transfusion (2.2% vs 1.4%),
and death (1.2% vs 0.7%) (p <0.001); >10% of patients were given prasugrel or
ticagrelor for a non-ACS indication. Ticagrelor is prescribed to a higher risk
population, and 1 in 10 patients prescribed ticagrelor or prasugrel did not have
ACS.
PMID- 25846768
TI - Relation of polymorphism of the histidine decarboxylase gene to chronic heart
failure in Han Chinese.
AB - Histidine decarboxylase (HDC) is a key determinant of the levels of endogenous
histamine that has long been recognized to play important pathophysiological
roles during development of chronic heart failure (CHF). Meanwhile, certain
genetic variants in HDC gene were reported to affect the function of HDC and
associated with histamine-related diseases. However, the relation between
polymorphisms of HDC gene and CHF risk remains unclear. This study aims to
investigate the associations between 2 nonsynonymous HDC polymorphisms
(rs17740607 and rs2073440) and CHF. We designed a 2-stage case-control study, in
which we genotyped 439 patients with CHF and 467 healthy controls recruited in
Xi'an, China, and replicated this study in 413 patients with CHF and 452 healthy
subjects in Kunming, China. We also performed in vitro experiments to further
validate the functional consequences of variants positively associated with CHF.
The rs17740607 polymorphism showed replicated associations with all-cause CHF
according to genotype and allele distribution and also under a dominant and
additive genetic model after adjusted for traditional cardiovascular-related
factors. Functional experiments further demonstrated that rs17740607 polymorphism
decreased the HDC activity. In conclusion, HDC rs17740607 polymorphism is at
least a partial loss-of-function variant and acts as a protective factor against
CHF, which provides novel highlights for investigating the contribution of CHF.
PMID- 25846769
TI - H19 lncRNA mediates 17beta-estradiol-induced cell proliferation in MCF-7 breast
cancer cells.
AB - Estrogen plays a critical role in breast cancer development and progression.
However, the mechanism involved in the promotion of breast cancer development and
progression by estrogen remains unclear although it has been intensively studied.
In the present study, we investigated the estrogen inducibility and functional
significance of H19 lncRNA in breast cancer cells and tumor tissues. The
screening of 83 disease-related long non-coding RNAs (lncRNAs) revealed that H19
lncRNA was much higher in estrogen receptor (ER)-positive MCF-7 breast cancer
cells than in ER-negative MDA-MB-231 cells. 17beta-estradiol produced a dose- and
time-dependent induction of H19 expression in MCF-7 cells, which was mediated via
ERalpha as evident by the blockade of this 17beta-estradiol effect with ICI
182780, a specific ER antagonist and knockdown of ERalpha using specific RNAi.
Moreover, knockdown of H19 lncRNA decreased cell survival and blocked estrogen
induced cell growth while overexpression of H19 lncRNA stimulated cell
proliferation. Quantitation of H19 lncRNA in human breast cancer tissues showed
that the level of H19 lncRNA was >10-fold higher in ER-positive than in ER
negative tumor tissues. These results suggest that H19 is an estrogen-inducible
gene and plays a key role in cell survival and in estrogen-induced cell
proliferation in MCF-7 cells, indicating that H19 lncRNA may serve as a biomarker
for breast cancer diagnosis and progression, and as a valuable target for breast
cancer therapy.
PMID- 25846770
TI - A case of colonic solitary polypoid ganglioneuroma with a feature of inverted
hyperplastic polyp.
PMID- 25846771
TI - Boy Crisis? Sex Differences in Self-Injurious Behaviors and the Effects of Gender
Role Conflicts Among College Students in China.
AB - In Western research, self-injurious behaviors are commonly viewed as "feminine"
behavior. In this present study, using the data from a survey administered to 960
first- and second-year students in Xi'an Jiaotong University in China, the self
injurious behaviors among college students are analyzed by sex. The results
reported that the average prevalence of self-injurious behaviors among male
students is 35.2%, higher than the 20.4% observed among female students (p < .1),
and the average frequency of severe self-injurious behaviors among male students
is 0.4, higher than the 0.18 reported among female students (p < .05). Gender
role conflicts and verbal violence are strongly associated with male students'
self-injurious behaviors, whereas gender role conflicts and verbal, visual, and
sexual violence are strongly associated with female students' self-injurious
behaviors. This suggests that self-injurious behaviors among college students in
China constitute, to some extent, a boy crisis that can be well explained by
gender role conflicts. In addition, verbal violence leads to self-injurious
behaviors among both male and female students, whereas visual and sexual violence
lead to self-injurious behaviors only among female students.
PMID- 25846779
TI - Elevated GFAP Protein in Anterior Cingulate Cortical White Matter in Males With
Autism Spectrum Disorder.
AB - Based on evidence of abnormalities in axon thickness and neuronal
disorganization, autism spectrum disorder (ASD) is commonly considered to be a
condition resulting from neuronal dysfunction. Yet, recent findings suggest that
non-neuronal cell types also contribute to ASD pathology. To investigate the role
of glial cells in ASD, a combination of protein and gene expression analyses were
used to determine levels of two glial markers, glial fibrillary acidic protein
(GFAP) and myelin oligodendrocyte glycoprotein (MOG), in the postmortem brain
tissue from control and ASD donors. Levels of GFAP immunoreactivity (ir) were
significantly elevated (P = 0.008) in anterior cingulate cortex (Brodmann area
24; BA24) white matter of ASD donors compared to control donors. In contrast,
GFAP-ir levels were similar in BA24 gray matter from ASD and control donors. MOG
ir was also similar in both BA24 white and gray matter from ASD and control
donors. In anterior prefrontal cortex (BA10), there were no significant
differences in GFAP-ir or MOG-ir in either white or gray matter comparing ASD to
control donors. Levels of expression of the genes GFAP and MOG also showed no
differences between control and ASD donors in BA24 and BA10 white and gray
matter. Collectively, these data imply that ASD is associated with an activation
of white matter astrocytes in the anterior cingulate cortex as a result of a yet
undefined cellular insult. Research is needed to investigate the molecular
pathways that underlie this astrocyte reaction and such research may yield
important clues regarding the etiology of ASD.
PMID- 25846772
TI - Adaptation of a Couple-Based HIV/STI Prevention Intervention for Latino Men Who
Have Sex With Men in New York City.
AB - Predominantly Spanish-speaking Latino men who have sex with men (MSM) and their
same-sex partners continue to be at high risk for HIV and STIs. Behavioral
research has identified how relationship dynamics for male couples are associated
with sexual risk behavior. Connect 'n Unite (CNU), an evidence-based HIV/STI
prevention intervention originally created for Black MSM and their same-sex
partners, was adapted for predominantly Spanish-speaking Latino MSM and their
same-sex partners on the assumption that its key elements would be translatable
while its efficacy would be retained. A systematic adaptation process utilizing
qualitative methods was used, including intervention adaptation sessions with 20
predominantly Spanish-speaking Latino gay couples and 10 health service
providers. The process included five steps: (1) engaging community stakeholders,
(2) capturing the lived experiences of Latino gay couples, (3) identifying
intervention priorities, (4) integrating the original intervention's social
cognitive theory into a relationship-oriented, ecological framework for Latino
gay couples, and (5) adapting intervention activities and materials. The adapted
intervention, which we called Latinos en Pareja or Latinos in a Relationship,
incorporates elements that effective HIV prevention interventions share,
including: a solid theoretical foundation; emphasis on increasing risk reduction
norms, sexual communication skills and social support for protection; and
guidance on how to utilize available, culturally and linguistically appropriate
services. The systematic adaptation approach used for a couples-based HIV
prevention intervention also can be employed by other researchers and community
stakeholders to adapt evidence-based interventions that promote wellness, linkage
to care, and disease prevention for populations not originally targeted.
PMID- 25846780
TI - The use and abuse of questionnaires in veterinary medicine.
PMID- 25846794
TI - Response to: Fuller et al., "Glenosphere disengagement in a reverse total
shoulder arthroplasty with a non-Morse taper design".
PMID- 25846795
TI - The prevalence of developmental dysplasia of the hip in idiopathic clubfoot: a
systematic review and meta-analysis.
AB - PURPOSE: Developmental dysplasia of the hip (DDH) and idiopathic clubfoot are
both common paediatric orthopaedic conditions. There is conflicting evidence in
the literature as to whether the prevalence of DDH is higher in children with
idiopathic clubfoot. The aim of our study was to systematically review the
literature and determine the prevalence of DDH in idiopathic clubfoot. METHODS:
We searched several databases from 1946 to 2014 for observational studies that
reported the prevalence of DDH in idiopathic clubfoot. We performed a meta
analysis using random effects model to pool the prevalence of DDH in idiopathic
clubfoot. We also investigated the imaging modality utilised to diagnose and
treat DDH in idiopathic clubfoot. Descriptive, quantitative and qualitative data
were extracted. RESULTS: Twelve studies (ten case series, one retrospective
cohort and one retrospective case-control) were eligible for the meta-analysis,
with a total of 2,549 children with idiopathic clubfoot including 83 with DDH.
The pooled prevalence estimate of DDH in children with idiopathic clubfoot was
4.1% (95% CI, 2.1-7.7%). There was a substantial amount of between study
heterogeneity (I (2) = 87.1%, p < 0.001) due to variability between studies
rather than chance variability. Sensitivity analyses showed that the pooled
prevalence estimate was 3.5% (95% CI, 1.1-10.8 %) and 3.8% (95% CI, 1.0-13.7%)
for studies utilising ultrasound as the imaging modality of diagnosis and
treatment with a Pavlik harness respectively. CONCLUSIONS: The overall pooled
prevalence of DDH in idiopathic clubfoot is similar to the normal population. The
cumulative evidence at present does not indicate an association between DDH and
idiopathic clubfoot. Therefore, we do not recommend routine screening for DDH in
children with idiopathic clubfoot. However, future retrospective and/or
prospective cohort studies of better quality will be able to answer this question
with more certainty.
PMID- 25846796
TI - Oxygen-sensing PHDs regulate bone homeostasis through the modulation of
osteoprotegerin.
AB - The bone microenvironment is composed of niches that house cells across variable
oxygen tensions. However, the contribution of oxygen gradients in regulating bone
and blood homeostasis remains unknown. Here, we generated mice with either single
or combined genetic inactivation of the critical oxygen-sensing prolyl
hydroxylase (PHD) enzymes (PHD1-3) in osteoprogenitors. Hypoxia-inducible factor
(HIF) activation associated with Phd2 and Phd3 inactivation drove bone
accumulation by modulating osteoblastic/osteoclastic cross-talk through the
direct regulation of osteoprotegerin (OPG). In contrast, combined inactivation of
Phd1, Phd2, and Phd3 resulted in extreme HIF signaling, leading to polycythemia
and excessive bone accumulation by overstimulating angiogenic-osteogenic
coupling. We also demonstrate that genetic ablation of Phd2 and Phd3 was
sufficient to protect ovariectomized mice against bone loss without disrupting
hematopoietic homeostasis. Importantly, we identify OPG as a HIF target gene
capable of directing osteoblast-mediated osteoclastogenesis to regulate bone
homeostasis. Here, we show that coordinated activation of specific PHD isoforms
fine-tunes the osteoblastic response to hypoxia, thereby directing two important
aspects of bone physiology: cross-talk between osteoblasts and osteoclasts and
angiogenic-osteogenic coupling.
PMID- 25846798
TI - Cytotoxic response of platinum-coated gold nanorods in human breast cancer cells
at very low exposure levels.
AB - Because of unique optical behavior gold nanorods (GNRs) have attracted attention
for the application in biomedical field such as bio-sensing, bio-imaging and
hyperthermia. However, toxicological response of GNRs is controversial due to
their different surface coating. Therefore, a comprehensive knowledge about
toxicological profile of GNRs is necessary before their biomedical applications.
First time, we investigated the toxic response of GNRs coated with platinum (GNRs
Pt) in human breast carcinoma (MCF-7) cells. Platinum coating further improves
the optical and catalytic properties of GNRs. Assays such as 3-(4,5
dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), neutral red uptake
(NRU) and lactate dehydroganase (LDH) assays have shown that GNRs-Pt induced
cytotoxicity at very low exposure levels (0.1-0.8 MUg mL-1 ). Accumulation of
cells in SubG1 phase and low mitochondrial membrane potential (JC-1 probe) in
treated cells suggest that GNRs-Pt induced cell death via apoptotic pathway.
Quantitative real-time PCR data demonstrated that mRNA expression of apoptotic
genes (bax, caspase-3 and caspase-9) were up-regulated while anti-apoptotic gene
bcl-2 was down-regulated in cells exposed to GNRs-Pt. We further observed the
higher activity of caspase-3 and caspase-9 enzymes in GNRs-Pt treated cells
supporting mRNA data. Moreover, N-acetyl cysteine (NAC) significantly attenuated
the ROS generation and cytotoxicity induced by GNRs-Pt in MCF-7 cells suggesting
that ROS might plays a crucial role in GNRs-Pt induced toxicity. This study warns
of possible toxicity of GNRs even at very low exposure levels. Further
investigations needed to explore potential mechanisms of this low dose toxicity
phenomenon. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1344-1356, 2016.
PMID- 25846799
TI - Introduction to Special Series: Deconstructing chronic low back pain in the older
adult: shifting the paradigm from the spine to the person.
PMID- 25846797
TI - Regulation of early T-lineage gene expression and developmental progression by
the progenitor cell transcription factor PU.1.
AB - The ETS family transcription factor PU.1 is essential for the development of
several blood lineages, including T cells, but its function in intrathymic T-cell
precursors has been poorly defined. In the thymus, high PU.1 expression persists
through multiple cell divisions in early stages but then falls sharply during T
cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it
has remained unknown how PU.1 activities could contribute positively to T-cell
development. Here we employed conditional knockout and modified antagonist PU.1
constructs to perturb PU.1 function stage-specifically in early T cells. We show
that PU.1 is needed for full proliferation, restricting access to some non-T
fates, and controlling the timing of T-cell developmental progression such that
removal or antagonism of endogenous PU.1 allows precocious access to T-cell
differentiation. Dominant-negative effects reveal that this repression by PU.1 is
mediated indirectly. Genome-wide transcriptome analysis identifies novel targets
of PU.1 positive and negative regulation affecting progenitor cell signaling and
cell biology and indicating distinct regulatory effects on different subsets of
progenitor cell transcription factors. Thus, in addition to supporting early T
cell proliferation, PU.1 regulates the timing of activation of the core T-lineage
developmental program.
PMID- 25846800
TI - A general catalytic reaction sequence to access alkaloid-inspired indole
polycycles.
AB - A catalytic two-step reaction sequence was developed to access a range of complex
heterocyclic frameworks based on biorelevant indole/oxindole scaffolds. The
reaction sequence includes catalytic Pictet-Spengler cyclization followed by
Au(I) catalyzed intramolecular hydroamination of acetylenes. A related cascade
polycyclization of a designed beta-carboline embodying a 1,5-enyne group yields
the analogues of the alkaloid harmicine.
PMID- 25846801
TI - The effect of various morphine weaning regimens on the sequelae of opioid
tolerance involving physical dependency, anxiety and hippocampus cell
neurodegeneration in rats.
AB - Chronic consumption of morphine induces physical dependency, anxiety, and
neurodegeneration. In this study, morphine on its own has been used for the
management of morphine-induced dependency, oxidative stress, and apoptosis. Forty
eight male rats were randomly divided into six groups. Rats in groups 1-5 were
made morphine dependent by an increasing manner of morphine for 7 days (15-45
mg/kg). For the next 14 days, morphine was administered using the following
regimen: (i) once daily 45 mg/kg (positive controls), (ii) the same dose at
additional intervals (6 h longer than the previous intervals each time), (iii) 45
mg/kg of morphine at irregular intervals like of 12, 24, 36 h, (iv) decreasing
dose once daily (every time 2.5 mg/kg less than the former dosage). Group 5
received 45 mg/kg of morphine and 10 mg/kg of SOD mimetic agent (M40401)
injection per day. Group 6 (negative control) received saline solution only. On
day 22, all animals received naloxone (3 mg/kg) and their Total Withdrawal Index
(TWI) and blood cortisol levels were measured. After drug treatment, hippocampus
cells were isolated, and oxidative, antioxidative, and apoptotic factors were
evaluated. Various regimens of morphine reduced TWI, cortisol levels, Bax
activity, caspase-3, caspase-9, TNF-alpha, and IL-1beta and lipid peroxidation.
In all treatment groups, GSH level, superoxide dismutase, glutathione peroxidase,
and Bcl-2 activity were significantly increased. Furthermore, SOD mimetic agent c
diminished morphine effect on SOD activity. Thus, varying the dosage regimen of
morphine can reduce the severity of morphine-induced dependency and
neurodegeneration.
PMID- 25846802
TI - A novel approach to tracer-kinetic modeling for (macromolecular) dynamic contrast
enhanced MRI.
AB - PURPOSE: To develop a novel tracer-kinetic modeling approach for multi-agent
dynamic contrast-enhanced MRI (DCE-MRI) that facilitates separate estimation of
parameters characterizing blood flow and microvascular permeability within one
individual. METHODS: Monte Carlo simulations were performed to investigate the
performance of the constrained multi-agent model. Subsequently, multi-agent DCE
MRI was performed on tumor-bearing mice (n = 5) on a 7T Bruker scanner on three
measurement days, in which two dendrimer-based contrast agents having high and
intermediate molecular weight, respectively, along with gadoterate meglumine,
were sequentially injected within one imaging session. Multi-agent data were
simultaneously fit with the gamma capillary transit time model. Blood flow, mean
capillary transit time, and bolus arrival time were constrained to be identical
between the boluses, while extraction fractions and washout rate constants were
separately determined for each agent. RESULTS: Simulations showed that
constrained multi-agent model regressions led to less uncertainty and bias in
estimated tracer-kinetic parameters compared with single-bolus modeling. The
approach was successfully applied in vivo, and significant differences in the
extraction fraction and washout rate constant between the agents, dependent on
their molecular weight, were consistently observed. CONCLUSION: A novel multi
agent tracer-kinetic modeling approach that enforces self-consistency of model
parameters and can robustly characterize tumor vascular status was demonstrated.
PMID- 25846804
TI - Is cholesterol good or bad for your brain?--NMDARs have a say.
PMID- 25846803
TI - Breaking the ice! Predictors about communication between nonresident African
American fathers and sons about sex.
AB - BACKGROUND AND PURPOSE: Research on communication between resident and
nonresident African American fathers and their sons about sex has been
understudied. The purpose of this study is to determine the influence of
parenting variables, specifically, racial socialization and father involvement on
nonresident African American father-son communication about sex. METHODS: Data
for this study are from the Fathers and Sons Project. This intervention study is
designed to enhance relationships between nonresident African American fathers
and their 8-12 year old sons and to prevent risky health behaviors among sons.
The present study is based on 345 African American boys who completed baseline
face-to-face interviews. The average age of the sons was 10.2 years old (SD =
1.4), with an average of two siblings (SD = 1.53). RESULTS: Age and sons'
perceptions of more parental monitoring by their fathers were predictive of
increased communication about sex. Racial socialization messages explained
additional variance in communication about sex above other parenting variables
and controls. IMPLICATIONS FOR PRACTICE: Findings suggest when working with
African American families, providers who counsel parents, and in particular
provide outreach to fathers regarding communication about sex, are in a unique
position to enhance parenting communication skills about sexuality.
PMID- 25846805
TI - Health anxiety and hypochondriasis in the light of DSM-5.
AB - BACKGROUND: In the DSM-5, the diagnosis of hypochondriasis was replaced by two
new diagnositic entities: somatic symptom disorder (SSD) and illness anxiety
disorder (IAD). Both diagnoses share high health anxiety as a common criterion,
but additonal somatic symptoms are only required for SSD but not IAD. DESIGN: Our
aim was to provide empirical evidence for the validity of these new diagnoses
using data from a case-control study of highly health-anxious (n = 96), depressed
(n = 52), and healthy (n = 52) individuals. RESULTS: The individuals originally
diagnosed as DSM-IV hypochondriasis predominantly met criteria for SSD (74%) and
rarely for IAD (26%). Individuals with SSD were more impaired, had more often
comorbid panic and generalized anxiety disorders, and had more medical
consultations as those with IAD. Yet, no significant differences were found
between SSD and IAD with regard to levels of health anxiety, other
hypochondriacial characteristics, illness behavior, somatic symptom attributions,
and physical concerns, whereas both groups differed significantly from clinical
and healthy controls in all of these variables. CONCLUSION: These results do not
support the proposed splitting of health anxiety/hypochondriasis into two
diagnoses. Further validation studies with larger samples and additional control
groups are warranted to prove the validity of the new diagnoses.
PMID- 25846806
TI - Reliability and validity of the Duncan-Ely test for assessing rectus femoris
spasticity in patients with cerebral palsy.
AB - AIM: The aim of this study was to clarify the method of the Duncan-Ely test and
to estimate its interobserver reliability and validity by comparing it with three
dimensional gait analysis (3DGA). METHOD: This study included 36 consecutive
ambulatory patients with cerebral palsy (CP) who underwent preoperative 3DGA. The
Duncan-Ely test was performed during three different velocities (slow, gravity,
and fast). The interobserver reliability was assessed by three examiners. The
results of the test were compared with kinematic variables derived from the gait
analysis to assess the sensitivity and specificity of the test. The cut-off value
was determined at the point of trade-off between the highest sensitivity and
specificity. RESULTS: The intraclass correlation coefficient measuring
interobserver reliability of the Duncan-Ely test was greatest during fast
velocity (0.819). The sensitivity and specificity of the test during gravity
velocity for knee range of motion total were 63.0% and 100% respectively, with a
cut-off value of 78.3 degrees . The sensitivity and specificity of the test
during fast velocity for knee range of motion total were 66.7% and 100%
respectively, with a cut-off value of 65 degrees . INTERPRETATION: The Duncan-Ely
test shows excellent reliability in fast knee-flexion velocity, and good
sensitivity and specificity compared with 3DGA during physical examination as a
preoperative assessment of rectus femoris spasticity in patients with CP.
PMID- 25846808
TI - Effects of 50 Hz magnetic fields on gap junctional intercellular communication in
NIH3T3 cells.
AB - The present study focused on gap junctional intercellular communication (GJIC) as
a target for biological effects of extremely low-frequency (ELF) magnetic field
(MF) exposure. Fluorescence recovery after photobleaching microscopy (FRAP) was
used to visualize diffusion of a fluorescent dye between NIH3T3 fibroblasts
through gap junctions. The direct effect of 24 h exposure to 50 Hz MF at 0.4 or 1
mT on GJIC function was assessed in one series of experiments. The potential
synergism of MF with an inhibitor of GJIC, phorbol ester (TPA), was studied in
another series by observing FRAP when NIH3T3 cells were incubated with TPA for 1
h following 24 h exposure to MF. In contrast to other reports of ELF-MF effects
on GJIC, under our experimental conditions we observed neither direct inhibition
of GJIC nor synergism with TPA-induced inhibition from 50 Hz MF exposures.
PMID- 25846807
TI - Saprolegnia diclina IIIA and S. parasitica employ different infection strategies
when colonizing eggs of Atlantic salmon, Salmo salar L.
AB - Here, we address the morphological changes of eyed eggs of Atlantic salmon, Salmo
salar L. infected with Saprolegnia from a commercial hatchery and after
experimental infection. Eyed eggs infected with Saprolegnia spp. from 10 Atlantic
salmon females were obtained. Egg pathology was investigated by light and
scanning electron microscopy. Eggs from six of ten females were infected with S.
parasitica, and two females had infections with S. diclina clade IIIA; two
Saprolegnia isolates remained unidentified. Light microscopy showed S. diclina
infection resulted in the chorion in some areas being completely destroyed,
whereas eggs infected with S. parasitica had an apparently intact chorion with
hyphae growing within or beneath the chorion. The same contrasting pathology was
found in experimentally infected eggs. Scanning electron microscopy revealed that
S. parasitica grew on the egg surface and hyphae were found penetrating the
chorion of the egg, and re-emerging on the surface away from the infection site.
The two Saprolegnia species employ different infection strategies when colonizing
salmon eggs. Saprolegnia diclina infection results in chorion destruction, while
S. parasitica penetrates intact chorion. We discuss the possibility these
infection mechanisms representing a necrotrophic (S. diclina) vs. a facultative
biotrophic strategy (S. parasitica).
PMID- 25846810
TI - Diagnosis of truncus arteriosus in first trimester of pregnancy using
transvaginal four-dimensional color Doppler ultrasound.
PMID- 25846809
TI - Beta-interferon exposure and onset of secondary progressive multiple sclerosis.
AB - BACKGROUND AND PURPOSE: Beta-interferons (IFNbeta) are the most widely prescribed
drugs for patients with multiple sclerosis (MS). However, whether or not
treatment with IFNbeta can delay secondary progressive MS (SPMS) onset remains
unknown. Our aim was to examine the association between IFNbeta exposure and SPMS
onset in patients with relapsing-remitting MS (RRMS). METHODS: A retrospective
cohort study using British Columbia (Canada) population-based clinical and health
administrative data (1985-2008) was conducted. RRMS patients treated with IFNbeta
(n = 794) were compared with untreated contemporary (n = 933) and historical (n =
837) controls. Cohort entry was the first clinic visit during which patients
became eligible for IFNbeta treatment (baseline). The outcome was time from
baseline to SPMS onset. Cox regression models with IFNbeta as a time-dependent
exposure were adjusted for sex, and baseline age, disease duration, disability,
*socioeconomic status and *comorbidities (*available for the contemporary cohorts
only). Additional analyses included propensity score adjustment. RESULTS: The
median follow-up for the IFNbeta-treated, untreated contemporary and historical
controls were 5.7, 3.7 and 7.3 years, and the proportions of patients reaching
SPMS were 9.2%, 11.8% and 32.9%, respectively. After adjustment for confounders,
IFNbeta exposure was not associated with the risk of reaching SPMS when either
the contemporary or the historical untreated cohorts were considered (hazard
ratio 1.07; 95% confidence interval 0.93-1.48, and hazard ratio 1.04; 95%
confidence interval 0.74-1.46, respectively). Further adjustments and the
propensity score yielded results consistent with the main analysis. CONCLUSIONS:
Amongst patients with RRMS, use of IFNbeta was not associated with a delayed
onset of SPMS.
PMID- 25846811
TI - Negative regulation of the LKB1/AMPK pathway by ERK in human acute myeloid
leukemia cells.
AB - Adenosine monophosphate-activated protein kinase (AMPK) is a sensor for cellular
energy status. When the cellular energy level is decreased, AMPK is activated and
functions to suppress energy-consuming processes, including protein synthesis.
Recently, AMPK has received attention as an attractive molecular target for
cancer therapy. Several studies have revealed that the activation of AMPK by
chemical stimulators, such as metformin, induces apoptosis in a variety of
hematologic malignant cells. From another perspective, these results suggest that
the function of AMPK is impaired in hematologic tumor cells. However, the precise
mechanisms by which this impairment occurs are not well understood. In melanoma
cells, oncogenic BRAF constitutively activates the extracellular signal-regulated
kinase (ERK) pathway and phosphorylates liver kinase B1, an upstream activator of
5' adenosine monophosphate-activated protein kinase (AMPK), resulting in the
inactivation of liver kinase B1 and AMPK. In this study, we analyzed whether ERK
is involved in the suppression of AMPK activity using established and primary
human leukemia cells. We found an inverse correlation between the intensity of
ERK activity and the degree of AMPK activation after stimulation with either
glucose deprivation or metformin. We also found that the inhibition of ERK
activity by U0126 restored AMPK activation after metformin treatment.
Furthermore, a combined treatment with metformin and U0126 enhanced the
antileukemic activity of metformin. Importantly, metformin induced ERK activation
by suppressing the protein levels of dual specificity phosphatase 6, a negative
regulator of ERK. This crosstalk between AMPK and ERK could diminish the
antileukemic activity of metformin. Taken together, our present observations
suggest a novel therapeutic strategy for improving the efficacy of metformin in
treating leukemia.
PMID- 25846812
TI - Transcatheter stenting of the systemic-to-pulmonary artery shunt: A 7-year
experience from a single tertiary center.
AB - BACKGROUND: Systemic-to-pulmonary artery shunt (SPS) dysfunction can be
deleterious in shunt dependent patients and traditionally have undergone surgical
revision. Data on transcatheter stenting of SPS is limited. We sought to evaluate
feasibility, safety and outcomes of stenting SPS. METHODS: Retrospective review
of all patients who underwent transcatheter SPS stenting from 1/2006 to 12/2013.
RESULTS: Of 229 surgically implanted SPS, 25 transcatheter stent interventions
were performed in 22 patients. The majority had pulmonary atresia (n = 9) or HLHS
(n = 10). Their median age was 4 ms (range 10 days to 4 years) and median weight
4.9 kg (range 3-14). Nine had a central and 15 had a BT shunt with a median shunt
size of 3.75 mm (range 3-6). The interval from shunt placement to intervention
was 1.9 ms (range 4 days-3.8 years). The indication for intervention was
increasing cyanosis in10 patients and delaying final repair in 9. Two patients
were on ECMO at the time of intervention. The median shunt diameter increased
from 2.3 to 4.1 mm and oxygen saturation from 72 to 85% (P < 0.001). No intra
procedural complications were encountered. One patient died from aspiration
(autopsy demonstrated a patent shunt), 13 progressed to repair or next stage, 6
remain palliated with shunts as they are deemed unfit for the next stage and 2
are awaiting surgery. CONCLUSIONS: Stenting of systemic to pulmonary artery shunt
is a safe and effective procedure and avoids surgical re-intervention. It can be
performed both as a rescue procedure in patients with acute shunt occlusion and
as an elective procedure to palliate patients not yet suitable for subsequent
corrective or staged repair.
PMID- 25846813
TI - Prognostic value of epidermal growth factor receptor amplification and EGFRvIII
in glioblastoma: meta-analysis.
AB - OBJECTIVES: Epidermal growth factor receptor (EGFR) gene amplification and the
EGFRvIII mutation may have prognostic value in patients with glioblastoma. This
meta-analysis was to determine whether EGFR gene amplification or the EGFRvIII
mutation are predictors of survival in patients with glioblastoma and anaplastic
astrocytoma. MATERIALS AND METHODS: Medline, the Cochrane Central Register of
Controlled Trials, EMBASE, and Google Scholar databases were searched until July
31, 2014. Studies were selected for inclusion in the analysis if they included
patients with anaplastic astrocytoma and/or glioblastoma, EGFR and/or EGFRvIII
mutation status was reported, and overall survival (OS) data were reported.
RESULTS: Of 113 articles initially identified, only eight contained data with
respect to the outcome of interest and were included in the meta-analysis. The
number of cases ranged from 14 to 268, and the majority of patients were 60 or
more years of age. There was no significant difference in OS between EGFR
amplification-positive and EGFR amplification-negative glioblastoma patients
(pooled hazard ratio [HR] = 1.101, 95% confidence interval [CI] 0.845, 1.434, P =
0.475) or anaplastic astrocytoma patients (pooled HR = 1.455, 95% CI 0.852,
2.482, P = 0.169). There was no significant difference in OS between EGFRvIII
positive and EGFRvIII-negative glioblastoma patients (pooled HR = 1.321, 95% CI:
0.881-1.981, P = 0.178). Significant heterogeneity existed between the studies,
and the significance changed when the analysis was performed with studies removed
in turn. CONCLUSIONS: There is insufficient evidence that either EGFR
amplification or the EGFRvIII mutation has prognostic value in patients with
glioblastoma.
PMID- 25846814
TI - ULTRASONOGRAPHIC FEATURES OF CANINE GASTROINTESTINAL STROMAL TUMORS COMPARED TO
OTHER GASTROINTESTINAL SPINDLE CELL TUMORS.
AB - Canine gastrointestinal stromal tumors (GISTs) are a recent subtype of
gastrointestinal spindle cell tumor recognized with the increasing use of
immunohistochemistry. To our knowledge, no imaging features have been described
in immunostochemically confirmed canine GISTs. The objective of this
retrospective, cross-sectional study was to describe ultrasonographic features of
canine GISTs compared with other spindle cell tumors. Thirty-seven dogs with an
ultrasonographically visible gastrointestinal mass and a histopathologic
diagnosis of spindle cell neoplasia were examined. Immunohistochemistry staining
was performed for retrieved tissue samples to further differentiate the tumor
type and each sample was interpreted by a single veterinary pathologist.
Ultrasonographic features recorded examined included mass echogenicity,
homogeneity, presence of cavitation, layer of origin, bowel wall symmetry, and
loss of wall layering, location, size, vascularity, and evidence of perforation
or ulceration. Tumor types included 19 GISTs, eight leiomyosarcomas, six
leiomyomas, and four nonspecified sarcomas. Gastrointestinal stromal tumors were
significantly more likely to be associated (P < 0.03) with abdominal effusion
than other tumor types. There was overlap between the anatomical locations of all
tumors types with the exception of the cecum where all eight tumors identified
were GISTs. Besides location, there were no unique ultrasound features of GISTs
that would allow distinction from other gastrointestinal spindle cell tumors.
Similar to previous studies, GISTs appeared to be the most common spindle cell
tumor associated with the cecum in our sample of dogs. The high frequency of
abdominal effusion with GIST's was of unknown etiology could possibly have been
due to septic peritonitis.
PMID- 25846815
TI - Triple Raman Label-Encoded Gold Nanoparticle Trimers for Simultaneous Heavy Metal
Ion Detection.
AB - Here, a triple Raman label-encoded gold nanoparticle (AuNP) trimer is fabricated
for heavy metal ion detection. In the presence of target ions, the gold
nanoparticles modified with different Raman labels are assembled into trimers and
produce different enhancements of Raman reporters, which are functionalized as
Raman probes for simultaneous silver and mercury ion detection. Under optimized
conditions, the limits of detection of Ag(+) and Hg(2+) reach 8.42 * 10(-12) and
16.78 * 10(-12) m, respectively.
PMID- 25846816
TI - Urinary incontinence persisting after childbirth: extent, delivery history, and
effects in a 12-year longitudinal cohort study.
AB - OBJECTIVE: To investigate the extent of persistent urinary incontinence (UI) 12
years after birth, and association with delivery-mode history and other factors.
DESIGN: Twelve-year longitudinal cohort study. SETTING: Maternity units in
Aberdeen, Birmingham, and Dunedin. POPULATION: Women who returned questionnaires
3 months and 12 years after index birth. METHODS: Data on all births over a
period of 12 months were obtained from the units and then women were contacted by
post. MAIN OUTCOME MEASURE: Persistent UI reported at 12 years, with one or more
previous contact. RESULTS: Of 7879 women recruited at 3 months, 3763 (48%)
responded at 12 years, with 2944 also having responded at 6 years; non-responders
had similar obstetric characteristics. The prevalence of persistent UI was 37.9%
(1429/3763). Among those who had reported UI at 3 months, 76.4% reported it at 12
years. Women with persistent UI had lower SF12 quality of life scores. Compared
with having only spontaneous vaginal deliveries (SVDs), women who delivered
exclusively by caesarean section were less likely to have persistent UI (odds
ratio, OR 0.42, 95% CI 0.33-0.54). This was not the case in women who had a
combination of caesarean section and SVD births (OR 1.01, 95% CI 0.78-1.30).
Older age at first birth, greater parity, and overweight/obesity were associated
with persistent UI. Of 54 index primiparae with UI before pregnancy, 46 (85.2%)
had persistent UI. CONCLUSIONS: This study, demonstrating that UI persists to 12
years in about three-quarters of women, and that risk was only reduced with
caesarean section if women had no other delivery mode, has practice implications.
TWEETABLE ABSTRACT: A longitudinal study of 3763 women showed a prevalence of
persistent UI 12 years after birth of 37.9%.
PMID- 25846817
TI - Underutilisation of synchronised cardioversion.
PMID- 25846818
TI - Factors Contributing to Sexual Violence at Selected Schools for Learners with
Mild Intellectual Disability in South Africa.
AB - BACKGROUND: This paper reports part of the findings of a study which exposed
sexual violence in schools for learners with mild intellectual disability in
South Africa. Special attention was paid on factors contributing to such a
problem. METHODS: Data were collected using focus groups and individual
interviews with 16 learners with mild intellectual disability at two special
schools in South Africa. This was followed by individual interviews with the
school nurse and social worker, and an analysis of schools' books of incidents.
RESULTS: Factors contributing to sexual violence at schools for learners with
mild intellectual disability included: (i) peer pressure, (ii) concealment of
reported incidents of sexual violence, (iii) unsupervised areas linked to schools
and (iv) arranged relationships. CONCLUSION: The following suggestions are put
forth: (i) awareness programmes, (ii) sensitization of teachers about the
consequences and prevention of sexual violence, (iii) boundaries within which the
arranged relationship occurs, (iv) intensification of sexuality education and (v)
supervision around the school premises.
PMID- 25846819
TI - Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune
Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T
Cells.
AB - The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the
nervous system are not clear. We investigated whether KRGE has a beneficial
effect on acute and chronic experimental autoimmune encephalomyelitis (EAE).
Pretreatment (daily from 10 days before immunization with myelin basic protein
peptide) with KRGE significantly attenuated clinical signs and loss of body
weight and was associated with the suppression of spinal demyelination and glial
activation in acute EAE rats, while onset treatment (daily after the appearance
of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the
messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis
factor-alpha [TNF-alpha] and interleukin [IL]-1beta), chemokines (RANTES,
monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein
1alpha [MIP-1alpha]), adhesion molecules (intercellular adhesion molecule-1 [ICAM
1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell
adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal
cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE
significantly reduced the population of CD4(+), CD4(+)/IFN-gamma(+), and
CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the
downregulation of mRNA expression of IFN-gamma, IL-17, and IL-23 in the spinal
cord. On the other hand, KRGE pretreatment increased the population of
CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats,
corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord.
Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1)
significantly decreased behavioral impairment. These results strongly indicate
that KRGE has a beneficial effect on the development and progression of EAE by
suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T
cells. Additionally, pre- and onset treatment with KRGE alleviated neurological
impairment of myelin oligodendrocyte glycoprotein(35-55)-induced mouse model of
chronic EAE. These results warrant further investigation of KRGE as preventive or
therapeutic strategies for autoimmune disorders, such as multiple sclerosis.
PMID- 25846821
TI - A land plant-specific thylakoid membrane protein contributes to photosystem II
maintenance in Arabidopsis thaliana.
AB - The structure and function of photosystem II (PSII) are highly susceptible to
photo-oxidative damage induced by high-fluence or fluctuating light. However,
many of the mechanistic details of how PSII homeostasis is maintained under
photoinhibitory light remain to be determined. We describe an analysis of the
Arabidopsis thaliana gene At5g07020, which encodes an unannotated integral
thylakoid membrane protein. Loss of the protein causes altered PSII function
under high-irradiance light, and hence it is named 'Maintenance of PSII under
High light 1' (MPH1). The MPH1 protein co-purifies with PSII core complexes and
co-immunoprecipitates core proteins. Consistent with a role in PSII structure,
PSII complexes (supercomplexes, dimers and monomers) of the mph1 mutant are less
stable in plants subjected to photoinhibitory light. Accumulation of PSII core
proteins is compromised under these conditions in the presence of translational
inhibitors. This is consistent with the hypothesis that the mutant has enhanced
PSII protein damage rather than defective repair. These data are consistent with
the distribution of the MPH1 protein in grana and stroma thylakoids, and its
interaction with PSII core complexes. Taken together, these results strongly
suggest a role for MPH1 in the protection and/or stabilization of PSII under high
light stress in land plants.
PMID- 25846820
TI - (S)-Lacosamide Binding to Collapsin Response Mediator Protein 2 (CRMP2) Regulates
CaV2.2 Activity by Subverting Its Phosphorylation by Cdk5.
AB - The neuronal circuit remodels during development as well as in human
neuropathologies such as epilepsy. Neurite outgrowth is an obligatory step in
these events. We recently reported that alterations in the phosphorylation state
of an axon specification/guidance protein, the collapsin response mediator
protein 2 (CRMP2), play a major role in the activity-dependent regulation of
neurite outgrowth. We also identified (S)-LCM, an inactive stereoisomer of the
clinically used antiepileptic drug (R)-LCM (Vimpat(r)), as a novel tool for
preferentially targeting CRMP2-mediated neurite outgrowth. Here, we investigated
the mechanism by which (S)-LCM affects CRMP2 phosphorylation by two key kinases,
cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3beta (GSK-3beta).
(S)-LCM application to embryonic cortical neurons resulted in reduced levels of
Cdk5- and GSK-3beta-phosphorylated CRMP2. Mechanistically, (S)-LCM increased
CRMP2 binding to both Cdk5- and GSK-3beta without affecting binding of CRMP2 to
its canonical partner tubulin. Saturation transfer difference nuclear magnetic
resonance (STD NMR) and differential scanning fluorimetry (DSF) experiments
demonstrated direct binding of (S)-LCM to CRMP2. Using an in vitro luminescent
kinase assay, we observed that (S)-LCM specifically inhibited Cdk5-mediated
phosphorylation of CRMP2. Cross-linking experiments and analytical
ultracentrifugation showed no effect of (S)-LCM on the oligomerization state of
CRMP2. The increased association between Cdk5-phosphorylated CRMP2 and CaV2.2 was
reduced by (S)-LCM in vitro and in vivo. This reduction translated into a
decrease of calcium influx via CaV2.2 in (S)-LCM-treated neurons compared to
controls. (S)-LCM, to our knowledge, is the first molecule described to directly
inhibit CRMP2 phosphorylation and may be useful for delineating CRMP2-facilitated
functions.
PMID- 25846822
TI - Capillary growth, ultrastructure remodelling and exercise training in skeletal
muscle of essential hypertensive patients.
AB - AIM: The aim was to elucidate whether essential hypertension is associated with
altered capillary morphology and density and to what extent exercise training can
normalize these parameters. METHODS: To investigate angiogenesis and capillary
morphology in essential hypertension, muscle biopsies were obtained from m.
vastus lateralis in subjects with essential hypertension (n = 10) and
normotensive controls (n = 11) before and after 8 weeks of aerobic exercise
training. Morphometry was performed after transmission electron microscopy, and
protein levels of several angioregulatory factors were determined. RESULTS: At
baseline, capillary density and capillary-to-fibre ratio were not different
between the two groups. However, the hypertensive subjects had 9% lower capillary
area (12.7 +/- 0.4 vs. 13.9 +/- 0.2 MUm(2)) and tended to have thicker capillary
basement membranes (399 +/- 16 vs. 358 +/- 13 nm; P = 0.094) than controls.
Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2
and thrombospondin-1 were similar in normotensive and hypertensive subjects, but
tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive
group. After training, angiogenesis was evident by 15% increased capillary-to
fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen
area were increased by 7 and 15% in the hypertensive patients, whereas capillary
basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression
after training was increased in both groups, whereas VEGF receptor-2 was
decreased by 25% in the hypertensive patients(P < 0.05). CONCLUSION: Essential
hypertension is associated with decreased lumen area and a tendency for increased
basement membrane thickening in capillaries of skeletal muscle. Exercise training
may improve the diffusion conditions in essential hypertension by altering
capillary structure and capillary number.
PMID- 25846823
TI - Development of laser desorption imaging mass spectrometry methods to investigate
the molecular composition of latent fingermarks.
AB - For a century, fingermark analysis has been one of the most important and common
methods in forensic investigations. Modern chemical analysis technologies have
added the potential to determine the molecular composition of fingermarks and
possibly identify chemicals a suspect may have come into contact with.
Improvements in analytical detection of the molecular composition of fingermarks
is therefore of great importance. In this regard, matrix-assisted laser
desorption ionization (MALDI) and laser desorption ionization (LDI) imaging mass
spectrometry (IMS) have proven to be useful technologies for fingermark analysis.
In these analyses, the choice of ionizing agent and its mode of deposition are
critical steps for the identification of molecular markers. Here we propose two
novel and complementary IMS approaches for endogenous and exogenous substance
detection in fingermarks: sublimation of 2-mercaptobenzothiazol (2-MBT) matrix
and silver sputtering.
PMID- 25846824
TI - Standard assessments of frailty are validated predictors of mortality in
hospitalized patients with cirrhosis.
AB - The risk of morbidity and mortality for hospitalized patients with cirrhosis is
high and incompletely captured by conventional indices. We sought to evaluate the
predictive role of frailty in an observational cohort study of inpatients with
decompensated cirrhosis between 2010 and 2013. The primary outcome was 90-day
mortality. Secondary outcomes included discharge to a rehabilitation hospital, 30
day readmission, and length of stay. Frailty was assessed with three metrics:
activities of daily living (ADL), the Braden Scale, and the Morse fall risk
score. A predictive model was validated by randomly dividing the population into
training and validation cohorts: 734 patients were admitted 1358 times in the
study period. The overall 90-day mortality was 18.3%. The 30-day readmission rate
was 26.6%, and the rate of discharge to a rehabilitation facility was 14.3%.
Adjusting for sex, age, Model for End-Stage Liver Disease, sodium, and Charlson
index, the odds ratio for the effect of an ADL score of less than 12 of 15 on
mortality is 1.83 (95% confidence interval [CI] 1.05-3.20). A predictive model
for 90-day mortality including ADL and Braden Scale yielded C statistics of 0.83
(95% CI 0.80-0.86) and 0.77 (95% CI 0.71-0.83) in the derivation and validation
cohorts, respectively. Discharge to a rehabilitation hospital is predicted by
both the ADL (<12) and Braden Scale (<16), with respective adjusted odds ratios
of 3.78 (95% CI 1.97-7.29) and 6.23 (95% CI 2.53-15.4). Length of stay was
associated with the Braden Scale (<16) (hazard ratio = 0.63, 95% CI 0.44-0.91).
No frailty measure was associated with 30-day readmission. CONCLUSIONS: Readily
available, standardized measures of frailty predict 90-day mortality, length of
stay, and rehabilitation needs for hospitalized patients with cirrhosis.
PMID- 25846825
TI - The devil is in the details: genetic variation in introduced populations and its
contributions to invasion.
AB - The influence of genetic variation on invasion success has captivated researchers
since the start of the field of invasion genetics 50 years ago. We review the
history of work on this question and conclude that genetic variation-as surveyed
with molecular markers-appears to shape invasion rarely. Instead, there is a
significant disconnect between marker assays and ecologically relevant genetic
variation in introductions. We argue that the potential for adaptation to
facilitate invasion will be shaped by the details of genotypes affecting
phenotypes, and we highlight three areas in which we see opportunities to make
powerful new insights. (i) The genetic architecture of adaptive variation. Traits
shaped by large-effect alleles may be strongly impacted by founder events yet
more likely to respond to selection when genetic drift is strong. Large-effect
loci may be especially relevant for traits involved in biotic interactions. (ii)
Cryptic genetic variation exposed during invasion. Introductions have strong
potential to uncover masked variation due to alterations in genetic and
ecological environments. (iii) Genetic interactions during admixture of multiple
source populations. As divergence among sources increases, positive followed by
increasingly negative effects of admixture should be expected. Although generally
hypothesized to be beneficial during invasion, admixture is most often reported
among sources of intermediate divergence, supporting the possibility that
incompatibilities among divergent source populations might be limiting their
introgression. Finally, we note that these details of invasion genetics can be
coupled with comparative demographic analyses to link genetic changes to the
evolution of invasiveness itself.
PMID- 25846826
TI - Effective Tuning of Ketocyanine Derivatives through Acceptor Substitution.
AB - A series of ketocyanine derivatives possessing bis(diarylamino)fluorenyl donors
and variable acceptors installed at the bridging carbon atom were synthesized to
investigate how the electronic structure of the dye can be systemically tuned
through stabilization of the cyanine-like character of the donor by increasing
the acceptor strength. Analysis of the (1) H NMR spectra indicates that the
"charge-separated" species dominates in these dyes, given that carbons possessing
a positive or negative charge in the resonance structures of this state
purposefully shift downfield or upfield, respectively, depending on the strength
of the acceptor moiety. In DAA-Fl-PI, the acceptor strength and the gain of
acceptor aromaticity indicates a predisposition of the separated state, indicated
by asymmetry in the (1) H NMR spectrum, as well as uneven distribution of the
HOMO on the fluorenyl donor.
PMID- 25846827
TI - Comment on the extraordinary career of Professor Dr Simon van Creveld.
PMID- 25846828
TI - Distinct contribution of Toxoplasma gondii rhomboid proteases 4 and 5 to
micronemal protein protease 1 activity during invasion.
AB - Host cell entry by the Apicomplexa is associated with the sequential secretion of
invasion factors from specialized apical organelles. Secretion of micronemal
proteins (MICs) complexes by Toxoplasma gondii facilitates parasite gliding
motility, host cell attachment and entry, as well as egress from infected cells.
The shedding of MICs during these steps is mediated by micronemal protein
proteases MPP1, MPP2 and MPP3. The constitutive activity of MPP1 leads to the
cleavage of transmembrane MICs and is linked to the surface rhomboid protease 4
(ROM4) and possibly to rhomboid protease 5 (ROM5). To determine their importance
and respective contribution to MPP1 activity, in this study ROM4 and ROM5 genes
were abrogated using Cre-recombinase and CRISPR-Cas9 nuclease, respectively, and
shown to be dispensable for parasite survival. Parasites lacking ROM4
predominantly engage in twirling motility and exhibit enhanced attachment and
impaired invasion, whereas intracellular growth and egress is not affected. The
substrates MIC2 and MIC6 are not cleaved in rom4-ko parasites, in contrast,
intramembrane cleavage of AMA1 is reduced but not completely abolished. Shedding
of MICs and invasion are not altered in the absence of ROM5; however, this
protease responsible for the residual cleavage of AMA1 is able to cleave other
AMA family members and exhibits a detectable contribution to invasion in the
absence of ROM4.
PMID- 25846829
TI - A new method for studying population genetics of cyst nematodes based on Pool-Seq
and genomewide allele frequency analysis.
AB - Cyst nematodes are important agricultural pests responsible for billions of
dollars of losses each year. Plant resistance is the most effective management
tool, but it requires a close monitoring of population genetics. Current
technologies for pathotyping and genotyping cyst nematodes are time-consuming,
expensive and imprecise. In this study, we capitalized on the reproduction mode
of cyst nematodes to develop a simple population genetic analysis pipeline based
on genotyping-by-sequencing and Pool-Seq. This method yielded thousands of SNPs
and allowed us to study the relationships between populations of different
origins or pathotypes. Validation of the method on well-characterized populations
also demonstrated that it was a powerful and accurate tool for population
genetics. The genomewide allele frequencies of 23 populations of golden nematode,
from nine countries and representing the five known pathotypes, were compared. A
clear separation of the pathotypes and fine genetic relationships between and
among global populations were obtained using this method. In addition to being
powerful, this tool has proven to be very time- and cost-efficient and could be
applied to other cyst nematode species.
PMID- 25846830
TI - Serum microRNAs as Potential Biomarkers of Juvenile Idiopathic Arthritis.
AB - MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression of targeted
mRNAs, which are important in the pathogenesis of autoimmune diseases. MiRNAs may
have the potential to serve as biomarkers of disease. We evaluated serum levels
of selected miRNAs and their associations with disease activity in juvenile
idiopathic arthritis (JIA). Sera and peripheral blood leukocytes were collected
from patients with JIA (8 systemic onset, 16 polyarthritis) and healthy controls.
Levels of miR-16, miR-132, miR-146a, miR-155, and miR-223 were quantified. Levels
of miR-223 in sera were significantly higher in patients in the active phase of
systemic onset JIA than in controls. MiRNAs of peripheral blood leukocytes did
not exhibit any difference between patients with JIA and controls. In both
systemic onset JIA and polyarthritis patients, levels of miR-223 and miR-16
correlated with erythrocyte sedimentation rate and matrix metalloproteinase-3,
respectively. MiR-146a and miR-223 in polyarthritis showed correlations with
matrix metalloproteinase-3. Expressions of miRNAs were altered in patients with
JIA. Serum levels of miR-223 may be a potential disease biomarker. Investigation
of miRNAs could be helpful in understanding the pathogenesis of JIA and could aid
in the identification of additional disease biomarkers.
PMID- 25846831
TI - Macrophage activation syndrome in the course of monogenic autoinflammatory
disorders.
AB - An overwhelming activation of cytotoxic T cells and well-differentiated
macrophages leading to systemic overload of inflammatory mediators characterizes
the so-called macrophage activation syndrome (MAS); this potentially life
threatening clinical entity may derive from several genetic defects involved in
granule-mediated cytotoxicity but has been largely observed in patients with
juvenile idiopathic arthritis, many rheumatologic diseases, infections, and
malignancies. The occurrence of MAS in the natural history or as the revealing
clue of monogenic autoinflammatory disorders (AIDs), rare conditions caused by
disrupted innate immunity pathways with overblown release of proinflammatory
cytokines, has been only reported in few isolated patients with cryopyrin
associated periodic syndrome, mevalonate kinase deficiency, familial
Mediterranean fever, and tumor necrosis factor receptor-associated periodic
syndrome since 2001. All these patients displayed various clinical, laboratory,
and histopathologic features of MAS and have often required intensive care
support. Only one patient has died due to MAS. Defective cytotoxic cell function
was documented in a minority of patients. Corticosteroids were the first-line
treatment, but anakinra was clinically effective in three refractory cases. Even
if MAS and AIDs share multiple clinical features as well as heterogeneous
pathogenetic scenes and a potential response to anti-interleukin-1 targeted
therapies, MAS requires a prompt specific recognition in the course of AIDs due
to its profound severity and high mortality rate.
PMID- 25846833
TI - Diagnosis and treatment of clinically amyopathic dermatomyositis (CADM): a case
series and literature review.
AB - The objective of this study was to report the clinical course of a cohort of
patients with clinically amyopathic dermatomyositis (CADM) in correlation to the
presence or absence of anti-melanoma differentiation-associated gene 5 (MDA-5)
antibody. Five patients with CADM presented to our rheumatology unit between
September 1, 2011 and March 31, 2014. We hereby present their clinical course,
laboratory findings, imaging modalities, functional tests, and treatments
regimens. Our cohort included five patients, with a mean age of 41.8 +/- 17.7.
Three patients, all anti-MDA-5 antibody positive, developed rapidly progressive
interstitial lung disease (ILD) within 4.3 +/- 4.5 months of presentation. Two of
these patients succumbed to their disease within 30 months of diagnosis despite
intensive immunosuppressive therapy. The third anti-MDA-5-positive patient with
ILD is still stable, 20 months from disease onset, on massive combination
therapy. One patient developed CADM associated with the anti-p155/140 antibody, a
year after completing chemotherapy for non-seminomatous germ cell tumor. He
presented with a benign clinical course with no evidence of ILD and no recurrence
of malignancy after 20 months of follow-up. The fifth patient in our cohort, who
is anti-MDA-5 negative and has no evidence of malignancy, also enjoys a benign
clinical course. The presence of anti-MDA-5 antibodies in CADM patients is
associated with rapidly progressive ILD and a poor prognosis. The serologic
profile of patients with CADM should be routinely evaluated and integrated with
clinical data in the management of these patients.
PMID- 25846832
TI - Are temporomandibular joint signs and symptoms associated with magnetic resonance
imaging findings in juvenile idiopathic arthritis patients? A longitudinal study.
AB - The aims of this longitudinal study were to perform a comprehensive clinical
evaluation of temporomandibular joint (TMJ) and to investigate the association
between the clinical and magnetic resonance imaging (MRI) findings in the TMJs of
patients with juvenile idiopathic arthritis (JIA). Seventy-five patients with JIA
participated in this study. All patients underwent a rheumatological examination
performed by a paediatric rheumatologist, a TMJ examination performed by a single
dentist and an MRI with contrast of the TMJs. These examinations were scheduled
on the same date. The patients were examined again 1 year later. Twenty-eight
(37.3 %) patients reported symptoms at the first evaluation and 11 (14.7 %)
patients at the second evaluation. In relation to signs, 35 (46.7 %) of the
patients presented at least one sign at the first evaluation and 29 (38.7 %) at
the second. Intense contrast enhancement of TMJ was significantly associated with
disease activity (p < 0.001) at the first evaluation and a trend to significance
was observed at the second (p = 0.056), with poly/systemic subtypes (p = 0.028
and p = 0.049, respectively), with restricted mouth opening capacity (p = 0.013
and p = 0.001, respectively), with the presence of erosions at both evaluations
(p = 0.0001 and p < 0.0001, respectively) and with altered condylar shape at the
second evaluation (p = 0.0005). TMJ involvement is highly prevalent in JIA
patients, with asymptomatic children presenting severe structural alterations of
the TMJ. The TMJ should always be evaluated in JIA patients, even in the absence
of signs and symptoms.
PMID- 25846834
TI - Health-related quality of life assessed by LupusQoL questionnaire and SF-36 in
Turkish patients with systemic lupus erythematosus.
AB - The LupusQoL is a disease-specific health-related quality of life (HRQoL) measure
for patients with lupus. We conducted this study to compare the efficiency of
LupusQoL-TR (validated Turkish version of the LupusQoL questionnaire) with the 36
item Short-Form Health Survey (SF-36), a generic quality of life (QoL) scale, in
Turkish patients with lupus. Both questionnaires were conducted at a single visit
to the clinic. Disease activity was measured with the Systemic Lupus
Erythematosus Disease Activity Index (SLEDAI). Associations between the LupusQoL
TR and SF-36 domains were examined while also examining age, disease duration,
and disease activity for each questionnaire. Descriptive statistics, Spearman's
correlation coefficients, and Students t test were performed to analyze the data.
A total of 113 consecutive patients with lupus (F/M 108:5, mean age 40.6 +/- 11.9
years, mean disease duration 8.5 +/- 7.0 years) were included, and 69 % of these
were active. The median SLEDAI score was 2 (0-24), the mean global LupusQoL-TR
score was 60.9 +/- 23.3, and the mean SF-36 score was 41.2 +/- 9.0. There was a
significant correlation between LupusQoL-TR and SF-36 mean scores (r = 0.83; p <
0.001). QoL assessed by LupusQoL-TR and SF-36 did not correlate with disease
activity (r = -0.11; p = 0.244 and r = -0.03; p = 0.721, respectively). LupusQoL
TR and SF-36 questionnaires were beneficial instruments in evaluating HRQoL in
Turkish lupus patients. However, LupusQoL-TR and SF-36 were not associated with
SLEDAI scores, which suggested that QoL might be affected by other factors
besides disease activity, especially in clinically inactive or mildly active
patients.
PMID- 25846835
TI - A synthetic workflow for coordinated direct observation and genetic tagging
applied to a complex host-parasite interaction.
AB - An important aspect influencing host specificity is a parasite's compatibility,
or ability, to infect a potential host. Here, we examine the compatibility
between different trematode genotypes of the same species and several host
species. To execute this study, we developed a synthetic workflow which combines
the use of a fluorescent dye and standard molecular techniques to study host
parasite interactions and host specificity. The utility of the fluorescent dye,
BIODIPY FL C12, was evaluated to label and track larval trematodes during
experimental infections using the Cerithidea californica-trematode host-parasite
system. Our results showed that low dye concentrations (200 nM) did not
significantly affect survival or infectivity of Acanthoparyphium spinulosum and
proved to be useful for labeling cercariae. Parasites were genotyped based on
sequences from cytochrome oxidase subunit 1 (COI) and the nuclear internal
transcribed spacer 1 (ITS1) prior to labeling and experimental infections.
Samples with low COI PCR product yield were reamplified using the M13 tails to
obtain enough material for sequencing. Three parasite genotypes were recovered
and results from experimental infections demonstrated varying levels of host
specificity. Of the three host species used (C. californica, Polydora nuchalis,
Tagelus californianus), genotype B was unable to infect P. nuchalis. Genotype A
individuals were less likely to infect P. nuchalis than the other host species.
Additionally, genotype C was unable to infect any host offered in this study.
These findings reflect possible suboptimal pairings between parasite genotype and
host species. Furthermore, the present study provides procedures that are useful
for exploring parasite ecology at the molecular level.
PMID- 25846836
TI - A systematic review of sacral nerve stimulation for low anterior resection
syndrome.
AB - AIM: The efficacy of sacral nerve stimulation (SNS) in low anterior resection
syndrome (LARS) is largely undocumented. A review of the literature was carried
out to study this question. METHOD: Pubmed, Medline and Cochrane databases were
searched for relevant articles up to August 2014. Studies were included if they
evaluated the use of SNS following rectal resection and assessed at least one of
the following end-points: bowel function, quality of life and ano-neorectal
physiology. No restrictions on language or study size were made. RESULTS: Seven
papers were identified including one case report and six prospective case series.
These included 43 patients with a median follow-up of 15 months. After peripheral
nerve evaluation definitive implantation was carried out in 34 (79.1%) patients.
Overall, 32 (94.1%) of the 34 patients experienced improvement of symptoms which,
based on intention to treat, was 32/43 (74.4%). CONCLUSION: The review suggests
that SNS for faecal incontinence in LARS has success rates comparable to its use
for other forms of faecal incontinence.
PMID- 25846837
TI - Anorexia nervosa as a motivated behavior: Relevance of anxiety, stress, fear and
learning.
AB - The high comorbidity between anorexia nervosa (AN) and anxiety disorders is well
recognized. AN is a motivated behavioral disorder in which habit formation is
likely to contribute to the persistence of abnormal eating and exercise
behaviors. Secondary alterations in brain circuitry underlying the reward value
of food and exercise, along with disturbances in neuroendocrine hunger and
satiety signaling arising from starvation and excessive exercise, are likely
contributors to the maintenance of anorectic behaviors in genetically vulnerable
individuals. The potential role of fear conditioning in facilitating onset of AN,
or of impaired fear extinction in contributing to the high relapse rates observed
following weight restoration, is of interest. Evidence from animal models of
anxiety and human laboratory studies indicate that low estrogen impairs fear
extinction. Low estradiol levels in AN may therefore play a role in perpetuating
fear of food and fat in recently weight restored patients. Translational models
including the activity based anorexia (ABA) rodent model of AN, and neuroimaging
studies of fear extinction and conditioning, could help clarify the underlying
molecular mechanisms and neurocircuitry involved in food avoidance behaviors in
AN. Moreover, the adaptation of novel treatment interventions with efficacy in
anxiety disorders may contribute to the development of new treatments for this
impairing disorder.
PMID- 25846838
TI - Reproductive and sexual behaviour development of dam or artificially reared male
lambs.
AB - The objective of this study was to determine if artificially reared male lambs
differ from those reared by their mothers in their reproductive development and
sexual behaviour during the first breeding season and in their serum testosterone
to a GnRH challenge at the end of the first breeding season. Lambs were assigned
to two experimental groups: 1) artificially reared lambs, separated from their
dams 24-36h after birth (Week 0) and fed sheep milk until 10weeks of age (group
AR, n=14); and 2) lambs reared by their dams until 10weeks of age (group DR,
n=13). Reproductive parameters and sexual behaviour were recorded from Weeks 9 to
39. The GnRH challenge was performed on Week 40. Body weight, scrotal
circumference, gonado-somatic index, testosterone concentration and sperm
parameters were unaffected by group, but increased with age (P<0.0001). Lambs
reared by their mothers had greater values of gonado-somatic index on Weeks 9, 16
and 19 (P<0.05), and tended to reach puberty earlier than AR (22.9+/-0.7 vs.
25.1+/-1.1weeks, respectively, P=0.087). Lambs reared by their mothers presented
more lateral approaches and mount attempts than AR (P<0.05), and DR lambs
presented more mounts on Weeks 32 and 39 than AR (P<0.05). Blood testosterone
concentrations 3.5 and 4h after the GnRH challenge were higher in AR than in DR
lambs (P<0.05). In conclusion mother rearing promoted sexual behaviour and
reproductive performance of male lambs.
PMID- 25846839
TI - Acute exercise ameliorates craving and inhibitory deficits in methamphetamine: An
ERP study.
AB - This study aimed to determine the effect of acute exercise in the potential
context of non-pharmacological intervention for methamphetamine (MA)-related
craving; we additionally determine its effect on the inhibitory control induced
by standard and MA-related tasks according to behavioral and neuroelectric
measurements among MA-dependent individuals. The present study employed a within
subjects, counterbalanced design. A total of 24 participants who met the DSM-IV
criteria for MA dependence were recruited. The craving level, reaction time, and
response accuracy, as well as the event-related potential (ERP) components N2 and
P3, were measured following exercise and the control treatment in a
counterbalanced order. The exercise session consisted of an acute stationary
cycle exercise at a moderate intensity, whereas the control treatment consisted
of an active reading session. The self-reported MA craving was significantly
attenuated during, immediately following, and 50min after the exercise session
compared with the pre-exercise ratings, whereas the craving scores at these time
points following exercise were lower than those for the reading control session.
Acute exercise also facilitated inhibitory performance in both the standard and
MA-related Go/Nogo tasks. A larger N2 amplitude, but not a larger P3 amplitude,
was observed during both tasks in the exercise session and the Nogo condition
compared with the reading control session and the Go condition. This is the first
empirical study to demonstrate these beneficial effects of acute aerobic exercise
at a moderate intensity on MA-related craving and inhibitory control in MA
dependent individuals. These results suggest a potential role for acute aerobic
exercise in treating this specific type of substance abuse.
PMID- 25846840
TI - Evaluation of Toxocara cati Excretory-Secretory Larval Antigens in Serodiagnosis
of Human Toxocariasis.
AB - BACKGROUND: Toxocariasis is the clinical term that is applied to infection in the
human host with Toxocara species larvae. Serological tests are important tools
for the diagnosis of toxocariasis. The aim of this study was to evaluate the
excretory-secretory (ES) antigens of T. cati larvae using enzyme-linked
immunosorbent assay (ELISA) and also Western blotting for serodiagnosis of human
toxocariasis. METHOD: The ES antigens were prepared from T. cati third-stage
larvae. Serum samples were obtained from 33 confirmed cases of toxocariasis, 35
patients infected with other parasitic diseases, and 30 from healthy individuals
tested with ELISA and immunoblotting. RESULTS: The ELISA showed appropriate
performance in term of specificity (96.7%) and sensitivity (97.0%).
Electrophoretic analysis of T. cati ES antigens revealed a range of 20- to 150
kDa fractions. The highest sensitivity was achieved with 42- and 50-kDa
fractions. CONCLUSION: The ELISA analyses using T. cati ES antigens demonstrated
good sensitivity and specificity compared to T. canis ES as antigens for
diagnosis of human toxocariasis. Accordingly, application of Western blotting,
based on 42- and 50-kDa fractions of ES antigens, can be recommended for the
accurate diagnosis of toxocariasis.
PMID- 25846841
TI - Maternal lifestyle during pregnancy and child psychomotor development - Polish
Mother and Child Cohort study.
AB - BACKGROUND: Nowadays special attention is paid to prenatal exposures to maternal
lifestyle factors and their impact on a child development. AIM: The objective of
this study was to evaluate the impact of modifiable maternal lifestyle factors on
child neurodevelopment based on the Polish Mother and Child Cohort study.
MATERIAL AND METHODS: The current analysis included 538 mother-child pairs. The
following factors related to maternal lifestyle were considered: smoking and
environmental tobacco smoke (ETS) exposure (based on the cotinine level in
maternal saliva measured using LC-ESI+MS/MS method), alcohol consumption and
leisure-time physical activity (LTPA) in pregnancy, pre-pregnancy BMI, and folic
acid supplementations before and during pregnancy based on questionnaire data.
Psychomotor development was assessed in children at the ages of one and two by
the Bayley Scales of Infant and Toddler Development. RESULTS: Significant
association was observed between prenatal exposure to tobacco constituents and a
decreased child motor development in assessments performed at both ages (beta=
0.8, p=0.01; beta=-1.4, p<0.001). Maternal pre-pregnancy underweight was
associated with decreased language abilities at 12 months of age (beta=-5.2,
p=0.01) and cognitive and motor development at 24 months of age, for which the
associations were of borderline significance (p=0.06). The recommended level of
LTPA during pregnancy was beneficial for child language development at two years
of age (beta=4.8, p=0.02). For alcohol and folic acid consumption there were no
significant associations with any of the analyzed domains of child
neurodevelopment. CONCLUSIONS: Children prenatally exposed to tobacco compounds
and those of underweight mothers had a decreased psychomotor development. The
recommended level of LTPA during pregnancy had positive impact on child
development. These results underscore the importance of policies and public
health interventions promoting healthy lifestyle among women in reproductive age
and during pregnancy.
PMID- 25846842
TI - Digit ratio (2D:4D) and physical fitness (Eurofit test battery) in school
children.
AB - BACKGROUND: The relative lengths of the index finger to the ring finger (2D:4D)
is sexually dimorphic and is thought to be a correlate of prenatal sex steroids
(low 2D:4D=high prenatal testosterone and low prenatal oestrogen). In adults
there have been reports that low 2D:4D is consistently associated with high
sports performance. AIMS: To investigate correlations between 2D:4D and fitness
levels in children. STUDY DESIGN: Right 2D:4D and body size were measured, in
addition to flexibility, speed, endurance and strength (Eurofit tests). SUBJECTS:
922 boys and 835 girls (mean ages (years): 10.8 +/- 1.01 and 10.07 +/- 1.00
respectively). OUTCOME MEASURES: height, mass, BMI, triceps and subscapular
skinfolds, 20 m shuttle run, sit and reach, standing broad jump, hand grip
strength, 10 * 5m sprint, and the sit and reach test. RESULTS: Boys significantly
outperformed the girls in the 10 * 5m sprints, the 20 m shuttle run, standing
broad jump, and hand grip strength. In boys but not girls, 2D:4D was
significantly negatively correlated with scores in all these tests except the
standing broad jump. In girls but not boys, 2D:4D was significantly positively
correlated to stature, mass, BMI and waist circumference. CONCLUSIONS: It is
suggested that high prenatal testosterone and low prenatal oestrogen (low 2D:4D)
is implicated in high sprinting speed, endurance and hand grip strength in boys.
In girls low prenatal testosterone and high prenatal oestrogen is associated with
large body size.
PMID- 25846843
TI - Risk factors and consequences of conversion in laparoscopic major liver
resection.
AB - BACKGROUND: Although recent reports have suggested potential benefits of the
laparoscopic approach in patients requiring major hepatectomy, it remains unclear
whether conversion to open surgery could offset these advantages. This study
aimed to determine the risk factors for and postoperative consequences of
conversion in patients undergoing laparoscopic major hepatectomy (LMH). METHODS:
Data for all patients undergoing LMH between 2000 and 2013 at two tertiary
referral centres were reviewed retrospectively. Risk factors for conversion were
determined using multivariable analysis. After propensity score matching, the
outcomes of patients who underwent conversion were compared with those of matched
patients undergoing laparoscopic hepatectomy who did not have conversion,
operated on at the same centres, and also with matched patients operated on at
another tertiary centre during the same period by an open laparotomy approach.
RESULTS: Conversion was needed in 30 (13.5 per cent) of the 223 patients
undergoing LMH. The most frequent reasons for conversion were bleeding and
failure to progress, in 14 (47 per cent) and nine (30 per cent) patients
respectively. On multivariable analysis, risk factors for conversion were patient
age above 75 years (hazard ratio (HR) 7.72, 95 per cent c.i. 1.67 to 35.70; P =
0.009), diabetes (HR 4.51, 1.16 to 17.57; P = 0.030), body mass index (BMI) above
28 kg/m(2) (HR 6.41, 1.56 to 26.37; P = 0.010), tumour diameter greater than 10
cm (HR 8.91, 1.57 to 50.79; P = 0.014) and biliary reconstruction (HR 13.99, 1.82
to 238.13; P = 0.048). After propensity score matching, the complication rate in
patients who had conversion was higher than in patients who did not (75 versus
47.3 per cent respectively; P = 0.038), but was not significantly different from
the rate in patients treated by planned laparotomy (79 versus 67.9 per cent
respectively; P = 0.438). CONCLUSION: Conversion during LMH should be anticipated
in patients with raised BMI, large lesions and biliary reconstruction. Conversion
does not lead to increased morbidity compared with planned laparotomy.
PMID- 25846844
TI - Glycation of Wild-Type Apomyoglobin Induces Formation of Highly Cytotoxic
Oligomeric Species.
AB - Protein glycation is a non-enzymatic, irreversible modification of protein amino
groups by reactive carbonyl species leading to the formation of advanced
glycation end products (AGEs). Several proteins implicated in neurodegenerative
diseases have been found to be glycated in vivo and the extent of glycation is
related to the pathologies of the patients. Although it is now accepted that
there is a direct correlation between AGEs formation and the development of
neurodegenerative diseases related to protein misfolding and amyloid aggregation,
several questions still remain unanswered: whether glycation is the triggering
event or just an additional factor acting on the aggregation pathway. We have
recently shown that glycation of the amyloidogenic W7FW14F apomyoglobin mutant
significantly accelerates the amyloid fibrils formation providing evidence that
glycation actively participates to the process. In the present study, to test if
glycation can be considered also a triggering factor in amyloidosis, we evaluated
the ability of different glycation agents to induce amyloid aggregation in the
soluble wild-type apomyoglobin. Our results show that glycation covalently
modifies apomyoglobin and induces conformational changes that lead to the
formation of oligomeric species that are not implicated in amyloid aggregation.
Thus, AGEs formation does not trigger amyloid aggregation in the wild-type
apomyoglobin but only induce the formation of soluble oligomeric species able to
affect cell viability. The molecular bases of cell toxicity induced by AGEs
formed upon glycation of wild-type apomyoglobin have been also investigated.
PMID- 25846846
TI - Automated Analysis of Anterior Chamber Inflammation by Spectral-Domain Optical
Coherence Tomography.
AB - PURPOSE: This study was designed to determine the feasibility of anterior segment
optical coherence tomography (AS-OCT) to objectively image and quantify the
degree of AC inflammation. DESIGN: Prospective evaluation of a diagnostic test.
PARTICIPANTS: Patients with anterior segment involving uveitis. METHODS:
Observational case series of patients with uveitis. Single-line and 3-dimensional
(3D) volume AS-OCT scans were manually graded to evaluate for the presence or
absence of cells in the AC. Clinical grading scores were correlated to the number
of cells seen in each line scan. An automated algorithm was developed to measure
the number of cells seen in the 3D volume scan and compared with manual
measurements and clinical grading scores. MAIN OUTCOME MEASURES: Degree of
anterior segment inflammation. RESULTS: A total of 114 eyes from 76 patients were
imaged, 83 eyes with line scans and 31 eyes with volume scans. The average number
of cells on line scans was 0.13 for grade 0, 1.2 for grade 1/2+, 2.6 for grade
1+, 5.7 for grade 2+, 15.5 for grade 3+, and 41.2 for grade 4+. Spearman
correlation coefficient comparing clinical grade with the individual AS-OCT line
scans was 0.967 (P < 0.0001). The range of cells in the automated cell count of
3D volume scans was 13.60 to 1222; the range for manual cell counts was from 9.2
to 2245. The Spearman correlation coefficients were r = 0.7765 (P < 0.0001) and r
= 0.7484 (P < 0.0001) comparing the manual and automated cell counts with the
clinical grade, respectively. Spearman correlation coefficient comparing the
automatic cell counts with manual cell count in the 3D volume scan was 0.997 (P <
0.0001). CONCLUSIONS: Anterior segment OCT can be used to image and grade the
degree of AC inflammation. Clinical grading strongly correlates with the number
of cells on AS-OCT line scans and volume scans. The automated algorithm to
measure cell count had a high correlation to manual measurement of cells in the
3D volume scans. This modality could be used to objectively grade response to
treatment.
PMID- 25846845
TI - Population pharmacokinetic analysis of tacrolimus in Mexican paediatric renal
transplant patients: role of CYP3A5 genotype and formulation.
AB - AIMS: The aims of this study were (i) to develop a population pharmacokinetic
(PK) model of tacrolimus in a Mexican renal transplant paediatric population (n =
53) and (ii) to test the influence of different covariates on its PK properties
to facilitate dose individualization. METHODS: Population PK and variability
parameters were estimated from whole blood drug concentration profiles obtained
at steady-state using the non-linear mixed effect modelling software NONMEM(r)
Version 7.2. RESULTS: Tacrolimus PK profiles exhibited high inter-patient
variability (IPV). A two compartment model with first order input and elimination
described the tacrolimus PK profiles in the studied population. The relationship
between CYP3A5 genotype and tacrolimus CL/F was included in the final model. CL/F
in CYP3A5*1/*1 and *1/*3 carriers was approximately 2- and 1.5-fold higher than
in CYP3A5*3/*3 carriers (non-expressers), respectively, and explained almost the
entire IPV in CL/F. Other covariates retained in the final model were the
tacrolimus dose and formulation type. Limustin(r) showed markedly lower
concentrations than the rest of the formulations. CONCLUSIONS: Population PK
modelling of tacrolimus in paediatric renal transplant recipients identified the
tacrolimus formulation type as a significant covariate affecting the blood
concentrations and confirmed the previously reported significant effect of CYP3A5
genotype on CL/F. It allowed the design of a proposed dosage based on the final
model that is expected to help to improve tacrolimus dosing.
PMID- 25846848
TI - Single prolonged stress induces dysfunction of endoplasmic reticulum in a rat
model of post-traumatic stress disorder.
AB - The aim of the present study, was to investigate the involvement of the
endoplasmic reticulum (ER) in post-traumatic stress disorder (PTSD) by detecting
changes of ER chaperone protein 78 and ER-resident caspase 12 in the basolateral
amygdala after exposure to single prolonged stress (SPS). The established rat
model of PTSD was generated by exposure of the animals to SPS. The expression of
glucose-regulated protein 78 (GRP78) was examined by immunofluorescence, western
blot and reverse transcription-polymerase chain reaction (RT-PCR), and the
expression of caspase 12 was examined by western blot and RT-PCR. The
morphological changes of the ER were detected by transmission electron
microscopy. The results showed that GRP78 expression significantly increased when
compared to that in the control group 1 day after SPS exposure (P<0.05). The
expression of caspase 12 was also significantly upregulated after SPS exposure
and peaked at 7 days following SPS (P<0.05). Morphological evaluation showed that
a tumescent ER, ER vacuolization and degranulation of the ER were present
following SPS. In conclusion, the findings of the present study suggested that
SPS induced GRP78 and caspase 12 upregulation and morphological changes of the ER
in the amygdala, which may play important roles in the pathogenesis of PTSD rats.
PMID- 25846847
TI - Two-year outcomes of "treat and extend" intravitreal therapy for neovascular age
related macular degeneration.
AB - PURPOSE: To report 24-month outcomes of anti-vascular endothelial growth factor
(VEGF) therapy for treatment-naive eyes with neovascular age-related macular
degeneration (nAMD) using a treat and extend treatment regimen in routine
clinical practice. DESIGN: Database observational study. PARTICIPANTS: We
included treatment-naive eyes receiving predominantly ranibizumab for nAMD in
routine clinical practice treated using a treat and extend regimen that were
tracked in the Fight Retinal Blindness observational registry. METHODS: A cohort
of eyes treated by practitioners using exclusively a treat and extend regimen was
extracted from the Fight Retinal Blindness observational registry. MAIN OUTCOME
MEASURES: Change in visual acuity (VA) over 2 years and number of injections and
visits. RESULTS: Data from 1198 eyes from 1011 patients receiving anti-VEGF
therapy using a treat and extend regimen for treatment-naive nAMD between January
2007 and December 2012 and with 24-month follow-up were included in the analysis.
Mean VA increased by +5.3 logarithm of the minimum angle of resolution letters
from 56.5 letters (20/80+1) at initial visit to 61.8 (20/60+2) letters at 24
months. Mean VA gains improved and number of injections increased with successive
years from +2.7 letters for eyes commencing in 2007 after a mean of 9.7
injections in 2 years, to +7.8 letters for eyes commencing in 2012 after a mean
of 14.2 injections over 2 years. The proportion of eyes with VA >20/40 increased
from 27% when starting treatment to 45% after 24 months; the proportion with
vision of <20/200 remained unchanged (13% initial, 11% at 24 months). Of the
included eyes, 90.5% avoided a vision loss of >=15 letters. There was an overall
mean of 13.0 injections over the 24 months, 7.5 injections in the first year and
5.5 in the second year, with a mean of 14.8 clinic visits. CONCLUSIONS: These
data indicate that eyes managed in routine clinical practice with a treat and
extend regimen can achieve good visual outcomes while decreasing the burden of
treatments and clinic visits.
PMID- 25846849
TI - Old foes, new understandings: nuclear entry of small non-enveloped DNA viruses.
AB - The nuclear import of viral genomes is an important step of the infectious cycle
for viruses that replicate in the nucleus of their host cells. Although most
viruses use the cellular nuclear import machinery or some components of this
machinery, others have developed sophisticated ways to reach the nucleus. Some of
these have been known for some time; however, recent studies have changed our
understanding of how some non-enveloped DNA viruses access the nucleus. For
example, parvoviruses enter the nucleus through small disruptions of the nuclear
membranes and nuclear lamina, and adenovirus tugs at the nuclear pore complex,
using kinesin-1, to disassemble their capsids and deliver viral proteins and
genomes into the nucleus. Here we review recent findings of the nuclear import
strategies of three small non-enveloped DNA viruses, including adenovirus,
parvovirus, and the polyomavirus simian virus 40.
PMID- 25846850
TI - Gastroschisis and young mothers: What makes them different from other mothers of
the same age?
AB - BACKGROUND: Although young maternal age has been identified as a risk factor for
gastroschisis, its role remains undisclosed. To our knowledge, the differences
between young mothers of infants with gastroschisis and young mothers of infants
with other pregnancy outcomes have not been established. The aim of this work was
to compare characteristics of young mothers whose newborn had gastroschisis with
same aged mothers of malformed and nonmalformed control infants, diagnosed within
the ECLAMC maternity hospital network. METHODS: Data base records of live and
stillborn infants of one of three groups (with isolated gastroschisis, with 1 of
5 other isolated birth defects, and nonmalformed), and whose mothers were younger
than 20 years, were selected. Secular trends were obtained for all birth defects;
frequencies and odds ratios (OR) of demographic and reproductive variables were
compared among the 3 groups. Significantly associated variables were adjusted
with a multivariate regression. RESULTS: The association was higher with
gastroschisis 1) than with other birth defects for African ancestry, smoking,
adequate prenatal control and diagnosis 2) than with nonmalformed controls for
maternal illnesses and alcohol 3) and than both for previous pregnancy loss and
medication, mainly sex hormones. After adjustment, only previous pregnancy loss
maintained its significance when compared with malformed (OR = 2.34; 1.37-3.97; P
= 0.002), as well as with nonmalformed (OR = 3.43; 2.07-5.66; P < 0.001)
controls. CONCLUSION: A previous pregnancy loss was identified as the main risk
factor for gastroschisis, while an increased use of sex hormones, perhaps related
to the previous loss, could trigger a disruptive mechanism, due to their
thrombophilic effect.
PMID- 25846854
TI - Life expectancy in bipolar disorder.
AB - OBJECTIVE: Life expectancy in patients with bipolar disorder has been reported to
be decreased by 11 to 20 years. These calculations are based on data for
individuals at the age of 15 years. However, this may be misleading for patients
with bipolar disorder in general as most patients have a later onset of illness.
The aim of the present study was to calculate the remaining life expectancy for
patients of different ages with a diagnosis of bipolar disorder. METHODS: Using
nationwide registers of all inpatient and outpatient contacts to all psychiatric
hospitals in Denmark from 1970 to 2012 we calculated remaining life expectancies
for values of age 15, 25, 35 ? 75 years among all individuals alive in year 2000.
RESULTS: For the typical male or female patient aged 25 to 45 years, the
remaining life expectancy was decreased by 12.0-8.7 years and 10.6-8.3 years,
respectively. The ratio between remaining life expectancy in bipolar disorder and
that of the general population decreased with age, indicating that patients with
bipolar disorder start losing life-years during early and mid-adulthood.
CONCLUSIONS: Life expectancy in bipolar disorder is decreased substantially, but
less so than previously reported. Patients start losing life-years during early
and mid-adulthood.
PMID- 25846856
TI - Spatio-temporal variability in the cannibalistic behaviour of European hake
Merluccius merluccius: the influence of recruit abundance and prey availability.
AB - Cannibalistic behaviour of European hake Merluccius merluccius was studied
through the analysis of 49 836 gut contents belonging to individuals from 6 to 82
cm in total length (L(T)). Samples were collected every autumn between 1993 and
2009. The results showed that the consumption of conspecific individuals was
consistent over space and time. The abundance, spatial distribution patterns and
L(T) structure of M. merluccius recruits were the main variables involved in M.
merluccius cannibalism. A geographical pattern was found since increasing
cannibalism was observed in areas of recruit aggregations. The L(T) spectrum of
recruits in autumn was also a key factor and dependent on the spawning period.
When adults spawned from late spring to summer, an increasing cannibalism trend
was found in autumn, due to the ideal size structure of the prey (M. merluccius
recruits) for predators. Depth was also a significant variable, and a cannibal
peak was detected at depths ranging between 50 and 200 m, coinciding with a
spatial overlap of predator (pre-adults) and prey (recruits). The cannibalistic
behaviour of M. merluccius began at c. 12 cm, although 75% were mid-sized
individuals between 16 and 30 cm. Additionally, 90% of prey-hake were recruits
<18.5 cm. Some biological and ecological aspects such as growth rate, spawning
period, predation and competition interactions and the effect of some
oceanographic events on M. merluccius cannibalism are also discussed.
PMID- 25846855
TI - Do experimental units of different scale affect the biological performance of
European sea bass Dicentrarchus labrax larvae?
AB - The effects of different tank volumes (2000, 500 and 40 l) on European sea bass
Dicentrarchus labrax larval rearing, relating to growth, survival, quality and
stress variables, were investigated. A dynamic energy budget (DEB) model was used
to analyse the results. The hydrodynamics of the tanks exhibited differences,
with the water currents in the 2000 l tanks to be almost one order of magnitude
stronger than those in the 40 l ones. Important differences in fish growth were
observed between small and large tank-rearing volumes, with the smallest tank
resulting in the slowest growth. Based on the DEB model analysis, growth
differences were related to feeding rates, with growth in the smaller tank
limited by food availability. Differences in survival rates were not
statistically significant among the tank-rearing volumes. The quality evaluation
of the fry (in terms of swimbladder, jaw and skeletal abnormalities) showed
differences, with the smallest tank having the highest percentage of deformed
individuals. This could be attributed to both the feeding variances and the
hydrodynamics in the tanks. No differences were observed in terms of whole-body
cortisol at the two developmental stages; flexion, and when the larvae body was
fully covered by melanophores; when analysis was performed. This indicates that
the allostatic load exerted on fish of different groups was similar and inside
the fish-coping abilities range, in terms of the cortisol response axis. The
selection of the experimental scale is of importance, especially when the results
are to be transferred and applied on an industrial scale.
PMID- 25846857
TI - Growth and mortality of larval Myctophum affine (Myctophidae, Teleostei).
AB - The growth and mortality rates of Myctophum affine larvae were analysed based on
samples collected during the austral summer and winter of 2002 from south-eastern
Brazilian waters. The larvae ranged in size from 2.75 to 14.00 mm standard length
(L(S)). Daily increment counts from 82 sagittal otoliths showed that the age of
M. affine ranged from 2 to 28 days. Three models were applied to estimate the
growth rate: linear regression, exponential model and Laird-Gompertz model. The
exponential model best fitted the data, and L(0) values from exponential and
Laird-Gompertz models were close to the smallest larva reported in the literature
(c. 2.5 mm L(S)). The average growth rate (0.33 mm day(-1)) was intermediate
among lanternfishes. The mortality rate (12%) during the larval period was below
average compared with other marine fish species but similar to some epipelagic
fishes that occur in the area.
PMID- 25846858
TI - Comparison of the feeding apparatus and diet of European sardines Sardina
pilchardus of Atlantic and Mediterranean waters: ecological implications.
AB - In this study, the feeding apparatus (gill rakers, GR) and the diet composition
of European sardine Sardina pilchardus populations living in two contrasting
environments were compared: the upwelling area off western Iberia and the
comparatively less productive region of the north-western Mediterranean Sea. The
importance of local adaptations in the trophic ecology of this species was
estimated. Sardina pilchardus from the Atlantic Iberian coast and from the north
western Mediterranean Sea have clear differences in the feeding apparatus and
diet compositions. Those from the Atlantic Iberian coast have significantly more
GRs than S. pilchardus of the same size range in the Mediterranean Sea. While S.
pilchardus from the Mediterranean Sea mostly depend on prey ranging between 750
1500 and 3000-4000 um, corresponding mostly to cladocerans, decapods and
copepods, those from the Atlantic depend on smaller prey (50-500 and 1000-1500
um) that include phytoplankton and copepods, particularly during summer months,
and S. pilchardus eggs during the winter. The marked difference between the
trophic ecology of S. pilchardus in the two areas studied appears to have
originated from different dietary strategies that the two populations have
adopted in contrasting feeding environments. These differences are shown to
profoundly affect the size and quality of prey consumed, and the effect of
cannibalism on the populations.
PMID- 25846859
TI - Homogeneity of parasite assemblages of Dules auriga (Serranidae) in
hydrographically heterogeneous sites.
AB - Parasite assemblages of Dules auriga are described for the first time from
samples caught during research cruises in two localities of the Argentine
Uruguayan Common Fishing Zone (AUCFZ) and are compared with four additional
samples collected by commercial catches from the same region. A total of 178 fish
were examined and 13 parasite species were found. This showed low species
richness, a condition observed in some other small benthic species at a low
trophic level. The composition of the parasite fauna was similar to those found
on other host species in the region, sharing the same set of dominant species
with other sympatric fishes, which have been identified as both typical and as
indicators of this ecoregion: Grillotia carvajalregorum, Corynosoma australe and
Hysterothylacium sp. Multivariate similarity analyses at the infracommunity and
the component community levels indicated that the two samples caught at different
latitudes in the AUCFZ display almost identical parasite assemblages. This
repeatability in assemblage structure was also observed across samples from
commercial catches. The homogeneity of the parasite assemblages is considered to
be an intrinsic property of fish inhabiting the AUCFZ, independent of their
ecology and trophic level.
PMID- 25846860
TI - Otolith shape: a population marker for Atlantic herring Clupea harengus.
AB - Otolith shape variation of seven Atlantic herring Clupea harengus populations
from Canada, the Faroe Islands, Iceland, Ireland, Norway and Scotland, U.K.,
covering a large area of the species' distribution, was studied in order to see
if otolith shape can be used to discriminate between populations. The otolith
shape was obtained using quantitative shape analysis, transformed with Wavelet
and analysed with multivariate methods. Significant differences were detected
among the seven populations, which could be traced to three morphological
structures in the otoliths. The differentiation in otolith shape between
populations was not only correlated with their spawning time, indicating a strong
environmental effect, but could also be due to differing life-history strategies.
A model based on the shape differences discriminates with 94% accuracy between
Icelandic summer spawners and Norwegian spring spawners, which are known to mix
at feeding grounds. This study shows that otolith shape could become an accurate
marker for C. harengus population discrimination.
PMID- 25846861
TI - Diet and cannibalism in plainfin midshipman Porichthys notatus.
AB - The macroscopic and microscopic diversity of potential food items available in
the nests of plainfin midshipman Porichthys notatus were quantified and compared
with items that were found in the stomach and intestine (digestive tract) of the
guarding males. In this species, males occur as one of two possible reproductive
morphs: guarder males that care for young and sneaker males that parasitize the
courtship and care of guarder males. Although it was predicted that guarder males
would have fewer feeding opportunities due to their confinement to the nest, they
in fact had more food items in their digestive tracts than did sneaker males and
females. Date in the breeding season (a proxy of care duration) and body
condition were not correlated with the amount of food consumed by guarder males.
The main type of food consumed was P. notatus embryos; 69% of all guarder males
sampled had cannibalized offspring. By comparing the diet of both sexes and
tactics, this study sheds light on some of the strategies designed to cope with
the costs of providing parental care.
PMID- 25846862
TI - Spatio-temporal isotopic signatures (delta13 C and delta15 N) reveal that two
sympatric West African mullet species do not feed on the same basal production
sources.
AB - Potential trophic competition between two sympatric mullet species, Mugil
cephalus and Mugil curema, was explored in the hypersaline estuary of the Saloum
Delta (Senegal) using delta(13) C and delta(15) N composition of muscle tissues.
Between species, delta(15) N compositions were similar, suggesting a similar
trophic level, while the difference in delta(13) C compositions indicated that
these species did not feed from exactly the same basal production sources or at
least not in the same proportions. This result provides the first evidence of
isotopic niche segregation between two limno-benthophageous species belonging to
the geographically widespread, and often locally abundant, Mugilidae family.
PMID- 25846863
TI - Protein modification and maintenance systems as biomarkers of ageing.
AB - Changes in the abundance and post-translational modification of proteins and
accumulation of some covalently modified proteins have been proposed to represent
hallmarks of biological ageing. Within the frame of the Mark-Age project, the
workpackage dedicated to "markers based on proteins and their modifications" has
been firstly focused on enzymatic and non-enzymatic post-translational
modifications of serum proteins by carbohydrates. The second focus of the
workpackage has been directed towards protein maintenance systems that are
involved either in protein quality control (ApoJ/Clusterin) or in the removal of
oxidatively damaged proteins through degradation and repair (proteasome and
methionine sulfoxide reductase systems). This review describes the most relevant
features of these protein modifications and maintenance systems, their fate
during ageing and/or their implication in ageing and longevity.
PMID- 25846865
TI - Female sex of older patients is an independent risk factor for red blood cell
alloimmunization after transfusion.
AB - BACKGROUND: More women than men are encountered with red blood cell (RBC)
antibodies. It is not clear whether this difference is explained by more
immunizing events in women or by a different acting immune system. To assess
whether there is a difference in the posttransfusion RBC alloimmunization rate
between women and men, a study on RBC alloimmunization during a 5-year period was
conducted in patients with at least one antibody follow-up more than 14 days
after transfusion. STUDY DESIGN AND METHODS: Data on transfusion and antibody
follow-up characteristics in female and male transfusion recipients from the
Leiden University Medical Center laboratory database were collected. Hazard
ratios of alloimmunization, according to sex of the transfusion recipient, were
estimated using Cox proportional hazards regression models taking possible
confounders into account. RESULTS: From a total of 1699 women and 1969 men who
were eligible, 4.2% of women and 3.4% of men (relative risk, 1.3; 95% confidence
interval [CI], 0.9-1.8) developed posttransfusion antibodies. Adjustment for
confounders resulted in a relative 80% higher risk in women older than 45 years
of age. CONCLUSION: Elder women beyond childbearing age have a higher risk of
posttransfusion antibody formation compared to men.
PMID- 25846864
TI - Disturbed calcium signaling in spinocerebellar ataxias and Alzheimer's disease.
AB - Neurodegenerative disorders, such as spinocerebellar ataxias (SCAs) and
Alzheimer's disease (AD) represent a huge scientific and medical question, but
the molecular mechanisms of these diseases are still not clear. There is
increasing evidence that neuronal calcium signaling is abnormal in many
neurodegenerative disorders. Abnormal neuronal calcium release from the
endoplasmic reticulum may result in disturbances of cell homeostasis, synaptic
dysfunction, and eventual cell death. Neuronal loss is observed in most cases of
neurodegenerative diseases. Recent experimental evidence supporting the role of
neuronal calcium signaling in the pathogenesis of SCAs and AD is discussed in
this review.
PMID- 25846866
TI - Chronic toxicological effects of beta-diketone antibiotics on Zebrafish (Danio
rerio) using transcriptome profiling of deep sequencing.
AB - Transcriptome analysis is important for interpreting the functional elements of
the genome and revealing the molecular constituents of cells and tissues. Herein,
differentially transcribed genes were identified by deep sequencing after
zebrafish (Danio rerio) were exposed to beta-diketone antibiotics (DKAs); 23,129
and 23,550 mapped genes were detected in control and treatment groups, a total of
3238 genes were differentially expressed between control and treatment groups. Of
these genes, 328 genes (213 up- and 115 down-regulation) had significant
differential expression (p < 0.05) and an expression ratio (control/treatment) of
>2 or <0.5. Additionally, we performed Gene Ontology (GO) category and Kyoto
Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and found
266 genes in the treatment group with annotation terms linked to the GO category.
A total of 77 differentially expressed transcriptional genes were associated with
132 predicted KEGG metabolic pathways. Serious liver tissue damage was reflected
and consistent with the differences in genetic classification and function from
the transcriptome analysis. These results enhance our understanding of zebrafish
developmental processes under exposure to DKA stress. (c) 2015 Wiley Periodicals,
Inc. Environ Toxicol 31: 1357-1371, 2016.
PMID- 25846867
TI - Age-related T2 changes in hindlimb muscles of mdx mice.
AB - INTRODUCTION: Magnetic resonance imaging (MRI) was used to monitor changes in the
transverse relaxation time constant (T2) in lower hindlimb muscles of mdx mice at
different ages. METHODS: Young (5 weeks), adult (44 weeks), and old mdx (96
weeks), and age-matched control mice were studied. Young mdx mice were imaged
longitudinally, whereas adult and old mdx mice were imaged at a single time
point. RESULTS: Mean muscle T2 and percent of pixels with elevated T2 were
significantly different between mdx and control mice at all ages. In young mdx
mice, mean muscle T2 peaked at 7-8 weeks and declined at 9-11 weeks. In old mdx
mice, mean muscle T2 was decreased compared with young and adult mice, which
could be attributed to fibrosis. CONCLUSIONS: MRI captured longitudinal changes
in skeletal muscle integrity of mdx mice. This information will be valuable for
pre-clinical testing of potential therapeutic interventions for muscular
dystrophy.
PMID- 25846868
TI - Restoration of the anti-proliferative and anti-migratory effects of 1,25
dihydroxyvitamin D by silibinin in vitamin D-resistant colon cancer cells.
AB - Colorectal carcinoma (CRC) is the third most common cancer in developed
countries. A large fraction of cases are linked to chronic intestinal
inflammation, with concomitant increased TNF-alpha release and elevated
Snail1/Snail2 levels. These transcription factors in turn suppress vitamin D
receptor (VDR) expression, resulting in loss of responsiveness to the protective
anti-proliferative and anti-migratory effects of 1,25-dihydroxyvitamin D (1,25D).
Experimental and epidemiologic evidence support the use of natural products to
target CRC. Here we show that the flavonolignan silibinin reverses the TNF-alpha
induced upregulation of Snail1 and Snail2 in the 1,25D-resistant human colon
carcinoma cells HT-29. These silibinin effects are accompanied by an increase in
VDR levels; Snail1 overexpression reverses these silibinin effects. Silibinin
also restores promoter activity from a vitamin D-response element (VDRE) reporter
construct. While 1,25D had no significant effect on HT-29 and SW480-R cell
proliferation and migration, co-treatment with silibinin restored 1,25D
responsiveness. In addition, co-treatment with silibinin plus 1,25D decreased
proliferation and migration at doses where silibinin alone had no effect. These
findings demonstrate that this combination may present a novel approach to target
CRC in conditions of chronic colonic inflammation.
PMID- 25846870
TI - Serum free beta-human chorionic gonadotropin in the three trimesters of
pregnancy: effects of maternal characteristics and medical history.
AB - OBJECTIVE: To define the contribution of maternal variables which influence the
measured level of maternal serum free beta-human chorionic gonadotropin (beta
hCG) in screening for pregnancy complications. METHODS: Maternal characteristics
and medical history were recorded and serum free beta-hCG was measured in women
with a singleton pregnancy attending for three routine hospital visits at 11 + 0
to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For
pregnancies delivering phenotypically normal live births or stillbirths >= 24
weeks' gestation, variables from maternal demographic characteristics and medical
history that are important in the prediction of free beta-hCG were determined
from a linear mixed-effects multiple regression. RESULTS: Serum free beta-hCG was
measured in 94 985 cases in the first trimester, 7879 in the second trimester and
8424 in the third trimester. Significant independent contributions to serum free
beta-hCG were provided by gestational age, maternal weight, age and racial
origin, cigarette smoking, method of conception, diabetes mellitus and family
history of pre-eclampsia (PE) in the mother of the patient. The effects of some
variables were similar and those for others differed in each trimester. Random
effects multiple regression analysis was used to define the contribution of
maternal variables that influence the measured level of serum free beta-hCG and
express the values as multiples of the median (MoMs). The model was shown to
provide an adequate fit of MoM values for all covariates both in pregnancies that
developed PE and in those without this pregnancy complication. CONCLUSIONS: A
model was fitted to express measured serum free beta-hCG across the three
trimesters of pregnancy as MoMs after adjusting for variables from maternal
characteristics and medical history that affect this measurement.
PMID- 25846871
TI - Genetic variability of CYP2C19 in a Mexican population: contribution to the
knowledge of the inheritance pattern of CYP2C19*17 to develop the ultrarapid
metabolizer phenotype.
AB - CYP2C19 is a polymorphic enzyme that metabolizes a wide variety of therapeutic
drugs that has been associated with altered enzymatic activity and adverse drug
reactions. Differences in allele frequencies of the CYP2C19 gene have been
detected in populations worldwide. Thus, we analysed the alleles CYP2C19*2,
CYP2C19*3, CYP2C19*4 and CYP2C19*5 related to the poor metabolizer (PM) phenotype
in a Mexican population sample (n = 238), as well as CYP2C19*17, unique allele
related to ultrarapid metabolizer phenotype (UMs). Genotypes were determined
using SNaPshot and TaqManqPCR assays. In addition to the wild-type CYP2C19*1
allele (77.1%), we only found CYP2C19*17 (14.3%) and CYP2C19*2 (8.6%). Comparison
with previous population reports demonstrated that these two SNPs are
homogeneously distributed in Latin America (P > 0.05). Based on comparison with a
previous pharmacokinetic study that determined the frequency of CYP2C19
phenotypes in the same population (western Mexican), we obtained the following
findings: (i) based on the difference between the frequency of genotypes
CYP2C19*2/*2 (presumably PM) versus the observed prevalence of PM phenotypes (0.4
versus 6.3%; Chi(2) = 9.58, P = 0.00196), we inferred the plausible presence of
novel CYP2C19 alleles related to the PM phenotype; (ii) the prevalence of UMs was
in disagreement with the dominant inheritance pattern suggested for CYP2C19*17
(23.1 versus 4%; P < 0.00001); (iii) the apparent recessive inheritance pattern
of CYP2C19*17, based on the agreement between homozygous CYP2C19*17/*17
(presumably UMs) and the observed prevalence of UMs (2.1 versus 4%; (Chi(2) =
1.048; P = 0.306).
PMID- 25846869
TI - Patient-reported goal achievement following onabotulinumtoxinA treatment in
patients with neurogenic detrusor overactivity.
AB - AIMS: To identify the self-reported treatment goals of patients with urinary
incontinence (UI) due to neurogenic detrusor overactivity (NDO), determine
whether patients achieved their goals following onabotulinumtoxinA treatment, and
assess impact of neurogenic disease (multiple sclerosis or spinal cord injury)
and/or clean intermittent catheterization (CIC) on goal achievement. METHODS:
Data from two Phase III studies of onabotulinumtoxinA 200U (n = 227) or placebo
(n = 241) in NDO patients (>=14 UI episodes/week; inadequately managed by
anticholinergics) were pooled for analysis. At baseline, patients listed their
top two qualitative treatment goals, which were distributed into eight
subcategories. Six weeks post-treatment, patients rated whether they achieved
their goals (5-point Likert scale). The frequency distribution of goals, the
proportion of patients who achieved their goals, and goal achievement by etiology
and use/non-use of CIC were assessed. RESULTS: At baseline, the most common goals
were "be dry" (37.9%), "reduce other urinary symptoms" (26.4%), and "improve
quality of life/sleep/emotions" (21.4%). Significantly higher proportions of
onabotulinumtoxinA-treated patients achieved their overall goals versus placebo
(62.0% vs. 17.2%; P < 0.001). OnabotulinumtoxinA treatment resulted in higher
goal achievement in all goal categories, regardless of etiology. CIC use did not
negatively impact patients' overall goal achievement; significantly higher
proportions of onabotulinumtoxinA-treated patients versus placebo achieved their
goals regardless of baseline catheterization use or de novo CIC during the first
6 weeks of the study. CONCLUSIONS: The majority of patients with UI due to NDO
achieved their self-determined treatment goals following onabotulinumtoxinA 200U
therapy, regardless of etiology or CIC use. Neurourol. Urodynam. 35:595-600,
2016. (c) 2015 The Authors. Neurourology and Urodynamics, published by Wiley
Periodicals, Inc.
PMID- 25846872
TI - Genetic analysis of fertility restoration under CGMS system in rice (Oryza sativa
L.) using three-way test-cross method.
AB - We studied the genetics of fertility restoration by producing three-way test
cross (TWTC) hybrids involved different combinations of restorers, maintainers
and partial restorers of rice. Pollen and spikelet fertility of 16 TWTC hybrids
were studied. Six TWTC involving restorer/restorer combinations as male parents
produced progenies with fertility levels ranging from complete to zero. No
specific ratio of segregation was observed. The crosses involving
maintainer/maintainer combinations as male parents showed fully fertile and
partial fertile/sterile plants in their progenies. These could be due to
nonallelic gene interactions for fertility restoration between the two restorer
or maintainer parents, or due to the influence of some modifying genes in the
nuclear genome. TWTC involving partial restorer / restorer and partial
restorer/partial restorer as the male parents also produced fully fertile and
partial fertile/sterile plants suggesting the complex genetics of fertility
restoration in rice. There were no previous results depicting the complementation
effects of maintainers for fertility restoration.
PMID- 25846873
TI - Distinct patterns of epigenetic marks and transcription factor binding sites
across promoters of sense-intronic long noncoding RNAs.
AB - Long noncoding RNAs (lncRNAs) are a new class of noncoding RNAs that have been
extensively studied in the recent past as a regulator of gene expression,
including modulation of epigenetic regulation. The lncRNAs class encompasses a
number of subclasses, classified based on their genomic loci and relation to
protein-coding genes. Functional differences between subclasses have been
increasingly studied in the recent years, though the regulation of expression and
biogenesis of lncRNAs have been poorly studied. The availability of genome-scale
datasets of epigenetic marks has motivated us to understand the patterns and
processes of epigenetic regulation of lncRNAs. Here we analysed the occurrence of
expressive and repressive histone marks at the transcription start site (TSS) of
lncRNAs and their subclasses, and compared these profiles with that of the
protein-coding regions. We observe distinct differences in the density of histone
marks across the TSS of a few lncRNA subclasses. The sense-intronic lncRNA
subclass showed a paucity for mapped histone marks across the TSS which were
significantly different than all the lncRNAs and protein-coding genes in most
cases. Similar pattern was also observed for the density of transcription factor
binding sites (TFBS). These observations were generally consistent across cell
and tissue types. The differences in density across the promoter were
significantly associated with the expression level of the genes, but the
differences between the densities across long noncoding and protein-coding gene
promoters were consistent irrespective of the expression levels. Apart from
suggesting general differences in epigenetic regulatory marks across long
noncoding RNA promoters, our analysis suggests a possible alternative mechanism
of regulation and/or biogenesis of sense-intronic lncRNAs.
PMID- 25846874
TI - Simultaneous estimation of QTL effects and positions when using genotype data
with errors.
AB - Accurate genetic data are important prerequisite of performing genetic linkage
test or association test. Currently, most analytical methods assume that the
observed genotypes are correct. However, due to the constraint at the technical
level, most of the genetic data that people used so far contain errors. In this
paper, we considered the problem of QTL mapping based on biological data with
genotyping errors. By analysing all possible genotypes of each individual in
framework of multipleinterval mapping, we proposed an algorithm of inferring all
model parameters through the expectation-maximization (EM) algorithm and
discussed the hypothesis testing of the existence of QTL. We carried out
extensive simulation studies to assess the proposed method. Simulation results
showed that the new method outperforms the method that does not take the
genotyping errors into account, and therefore it can decrease the impact of
genotyping errors on QTL mapping. The proposed method was also applied to analyse
a real barley dataset.
PMID- 25846875
TI - Distribution of genes associated with yield potential and water-saving in Chinese
Zone II wheat detected by developed functional markers.
AB - Functional markers (FMs) developed from sequence polymorphisms are present in
allelic variants of a functional gene at a locus and are directly associated with
phenotypic variations. In this study, FM linked to Rht-B1, Rht-D1, TaCwi-A1,
TaSus2-2B, TaGW2-6A and Dreb-B1 genes conferring to yield potential and water
saving were selected to analyse the distribution in 102 wheat varieties, most of
which were authorized in the past decade and adapted to grow in Zone II of China.
First, the semidwarfing genes Rht-B1b and Rht-D1b (mutant alleles) conferring to
grain yield were analysed. The frequencies of favourable alleles Rht-B1b and Rht
D1b were 32.4 and 58.8%, respectively. Comparing with the previous report, the
frequency of Rht-B1b among cultivars in this study is similar to the frequency
among cultivars released in the 1990s, while the frequency of Rht-D1b is slightly
lower than the previous report 63.9%. Twelve (11.8%) cultivars neither contained
Rht-B1b nor Rht-D1b, while only Yumai 66 contained both semidwarfing genes.
Linyuan8 and Xinong 928 are heterozygous at RhtB1 locus and Zhengmai 9023 is
heterozygous at both RhtB1 and Rht-D1 loci. Second, the TaCwi-A1, TaSus2-2B and
TaGW2-6A genes considered as candidate genes related to grain weight were
detected. We found that the frequencies of the favourable alleles were 76.5, 56.9
and 69.6%, respectively. Among the 102 wheat varieties, 30 contained all the
three favourable genes, 45 contained two of the three favourable genes and 27
contained only one. There are eight wheat varieties (7.8%) in hybrid state at the
TaCWI-A1 locus. Third, the designed FM linked to water-saving gene Dreb-B1 were
validated on 102 wheat varieties. The results showed that the haplotypes of 47
wheat varieties at the Dreb-B1 locus were same as that of Opata 85, and 55 wheat
varieties showed the signal expected for W7984 (Opata 85 and W7984 are parents of
the ITMI mapping population). This information will be useful for the wheat
breeding programmes aiming at improving yield and water use efficiency in
Shijiazhuang located in China Zone II.
PMID- 25846876
TI - Inbreeding in stochastic subdivided mating systems: the genetic consequences of
host spatial structure, aggregated transmission dynamics and life history
characteristics in parasite populations.
AB - Inbreeding in parasite populations can have important epidemiological and
evolutionary implications. However, theoretical models have predominantly
focussed on the evolution of parasite populations under strong selection or in
epidemic situations, and our understanding of neutral gene dynamics in parasite
populations at equilibrium has been limited to verbal arguments or conceptual
models. This study focusses on how host-parasite population dynamics affects
observed levels of inbreeding in a random sample of parasites from an infinite
population of hosts by bridging traditional genetic and parasitological processes
utilizing a backward-forward branching Markov process embedded within a flexible
statistical framework, the logarithmic-poisson mixture model. My results indicate
that levels of inbreeding in parasites are impacted by demographic and/or
transmission dynamics (subdivided mating, aggregated transmission dynamics and
host spatial structure), and that this inbreeding is poorly estimated by
'equilibrium' levels of inbreeding calculated assuming regular systems of mating.
Specifically, the model reveals that at low levels of inbreeding (F <= 0.1),
equilibrium levels of inbreeding are lower than those observed, while at high
levels of inbreeding the opposite pattern occurs. The model also indicates that
inbreeding could have important epidemiological implications (e.g., the spread of
recessive drug resistance genes) by directly impacting the observed frequency of
rare homozygotes in parasite populations. My results indicate that frequencies of
rare homozygotes are affected by aggregated transmission dynamics and host
spatial structure, and also that an increase in the frequency of rare homozygotes
can be caused by a decrease in effective population size solely due to the
presence of a subdivided breeding system.
PMID- 25846877
TI - Identification of the trehalose-6-phosphate synthase gene family in winter wheat
and expression analysis under conditions of freezing stress.
AB - Trehalose plays an important role in metabolic regulation and abiotic stress
tolerance in plants. Trehalose contents are potentially modulated by trehalose-6
phosphate synthase (TPS), which is a key enzyme in the trehalose biosynthetic
pathway. Using available wheat expressed sequence tag sequence information from
NCBI and two wheat genome databases, we identified 12 wheat TPS genes and
performed a comprehensive study on their structural, evolutionary and functional
properties. The estimated divergence time of wheat TPS gene pairs and wheat-rice
orthologues suggested that wheat and rice have a common ancestor. The number of
TPS genes in the wheat genome was estimated to be at least 12, which is close to
the number found in rice, Arabidopsis and soybean. Moreover, it has been reported
earlier in other plants that TPS genes respond to abiotic stress, however, our
study mainly analysed the TPS gene family under freezing conditions in winter
wheat, and determined that most of the TPS gene expression in winter wheat was
induced by freezing conditions, which further suggested that wheat TPS genes were
involved in winter wheat freeze-resistance signal transduction pathways. Taken
together, the current study represents the first comprehensive study of TPS genes
in winter wheat and provides a foundation for future functional studies of this
important gene family in Triticeae.
PMID- 25846878
TI - Characterization and fine mapping of a female fertility associated gene Ff1(t) in
rice.
AB - Female-sterile line can be used as a pollinator which has a great potential for
hybrid seeds production. However, reports on female fertility are fewer than male
fertility. Here, we characterized a recessive female fertility weakening mutant
ff1(t) from rice. The spikelet fertility was seriously affected in the mutant.
Reciprocal crosses and pollen vitality assay suggest that the decreased fertility
was caused by the defective female gametophytes. Further investigation indicated
that the mutant ovary development was inhibited before fertilization and failed
swelling after flowering. Genetic analysis and fine mapping showed that the
mutant was controlled by a single recessive gene, residing on a 16.8 kb region on
the long arm of chromosome 1. The gene annotation indicated that there was only
one putative gene encoding lysine decarboxylase-like protein in this region,
which was allelic to LOG. Further, the sequence analysis was carried out and a
substitution at the splice site of intron 2 / exon 3 was revealed in ff1(t)
mutant, resulting in the change of reading frame. The finding of novel allele of
LOG locus will facilitate the understanding of the mechanisms of female
gametophyte development.
PMID- 25846879
TI - The effect of high glucose levels on the hypermethylation of protein phosphatase
1 regulatory subunit 3C (PPP1R3C) gene in colorectal cancer.
AB - DNA methylation is an epigenetic event that occurs frequently in colorectal
cancer (CRC). Increased glucose level is a strong risk factor for CRC. Protein
phosphatase 1 regulatory subunit 3C (PPP1R3C) modulates glycogen metabolism,
particularly glycogen synthesis. The aim of this study was to investigate the
effect of high glucose levels on DNA methylation of PPP1R3C in CRC. PPP1R3C was
significantly hypermethylated in CRC tissues (76/105, 72.38%, P <0.05) and colon
cancer cell lines (P < 0.05). CRC tissues obtained from patients with high
glucose levels showed that the methylation of PPP1R3C was lower than in patients
who had normal levels of glucose. When DLD-1 cells were cultured under conditions
of high glucose, the methylation of PPP1R3C was repressed. The expression of
PPP1R3C was inversely related to methylation status. In addition, a promoter
luciferase assay showed that the transcriptional activity of PPP1R3C was
increased in high glucose culture conditions. The number of cells decreased when
PPP1R3C was silenced in DLD-1 cells. These results suggest that PPP1R3C, a novel
hypermethylated gene in CRC, may play a critical role in cancer cell growth in
association with glucose levels.
PMID- 25846880
TI - Genetic diversity, population structure and marker trait associations for seed
quality traits in cotton (Gossypium hirsutum).
AB - Cottonseed contains 16% seed oil and 23% seed protein by weight. High levels of
palmitic acid provides a degree of stability to the oil, while the presence of
bound gossypol in proteins considerably changes their properties, including their
biological value. This study uses genetic principles to identify genomic regions
associated with seed oil, protein and fibre content in upland cotton cultivars.
Cotton association mapping panel representing the US germplasm were genotyped
using amplified fragment length polymorphism markers, yielding 234 polymorphic
DNA fragments. Phenotypic analysis showed high genetic variability for the seed
traits, seed oil range from 6.47-25.16%, protein from 1.85-28.45% and fibre
content from 15.88-37.12%. There were negative correlations between seed oil and
protein content.With reference to genetic diversity, the average estimate of FST
was 8.852 indicating a low level of genetic differentiation among subpopulations.
The AMOVA test revealed that variation was 94% within and 6% among
subpopulations. Bayesian population structure identified five subpopulations and
was in agreement with their geographical distribution. Among the mixed models
analysed, mixed linear model (MLM) identified 21 quantitative trait loci for lint
percentage and seed quality traits, such as seed protein and oil. Establishing
genetic diversity, population structure and marker trait associations for the
seed quality traits could be valuable in understanding the genetic relationships
and their utilization in breeding programmes.
PMID- 25846882
TI - Comparative analyses of genetic risk prediction methods reveal extreme diversity
of genetic predisposition to nonalcoholic fatty liver disease (NAFLD) among
ethnic populations of India.
AB - Nonalcoholic fatty liver disease (NAFLD) is a distinct pathologic condition
characterized by a disease spectrum ranging from simple steatosis to steato
hepatitis, cirrhosis and hepatocellular carcinoma. Prevalence of NAFLD varies in
different ethnic groups, ranging from 12% in Chinese to 45% in Hispanics. Among
Indian populations, the diversity in prevalence is high, ranging from 9% in rural
populations to 32% in urban populations, with geographic differences as well.
Here, we wished to find out if this difference is reflected in their genetic
makeup. To date, several candidate genes and a few genomewide association studies
(GWAS) have been carried out, and many associations between single nucleotide
polymorphisms (SNPs) and NAFLD have been observed. In this study, the risk allele
frequencies (RAFs) of NAFLD-associated SNPs in 20 Indian ethnic populations (376
individuals) were analysed. We used two different measures for calculating
genetic risk scores and compared their performance. The correlation of additive
risk scores of NAFLD for three Hapmap populations with their weighted mean
prevalence was found to be high (R(2) = 0.93). Later we used this method to
compare NAFLD risk among ethnic Indian populations. Based on our observation, the
Indian caste populations have high risk scores compared to Caucasians, who are
often used as surrogate and similar to Indian caste population in disease gene
association studies, and is significantly higher than the Indian tribal
populations.
PMID- 25846881
TI - De novo characterization of the alligator weed (Alternanthera philoxeroides)
transcriptome illuminates gene expression under potassium deprivation.
AB - As one of the three macronutrients, potassium participates in many physiological
processes in plant life cycle. Recently, potassium-dependent transcriptome
analysis has been reported in Arabidopsis, rice and soybean. Alligator weed is
well known, particularly for its strong ability to accumulate potassium. However,
the molecular mechanism that underlies potassium starvation responses has not yet
been described. In this study, we used Illumina (Solexa) sequencing technology to
analyse the root transcriptome information of alligator weed under low potassium
stress. Further analysis suggested that 9253 differentially expressed genes
(DEGs) were upregulated, and 2138 DEGs were downregulated after seven days of
potassium deficiency. These factors included 121 transcription factors, 108
kinases, 136 transporters and 178 genes that were related to stress. Twelve
transcription factors were randomly selected for further analysis. The expression
level of each transcription factor was confirmed by quantitative RT-PCR, and the
results of this secondary analysis were consistent with the results of Solexa
sequencing. Enrichment analysis indicated that 10,993 DEGs were assigned to 54
gene ontology terms and 123 KEGG pathways. Approximately 24% of DEGs belong to
the metabolic, ribosome and biosynthesis of secondary metabolite KEGG pathways.
Our results provide a comprehensive analysis of the gene regulatory network of
alligator weed under low potassium stress, and afford a valuable resource for
genetic and genomic research on plant potassium deficiency.
PMID- 25846883
TI - A novel missense mutation in collagenous domain of EDA gene in a Chinese family
with X-linked hypohidrotic ectodermal dysplasia.
PMID- 25846884
TI - Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and alcohol
consumption in hyperhomocysteinaemia: a population-based study from northeast
India.
PMID- 25846885
TI - Association of ACP1 gene polymorphisms and coronary artery disease in northeast
Chinese population.
PMID- 25846886
TI - Genetic evidence for susceptibility and resistance against scrapie in Indian
sheep.
PMID- 25846887
TI - Association of expression levels in skeletal muscle and a SNP in the MYBPC1 gene
with growth-related trait in Japanese Black beef cattle.
PMID- 25846888
TI - Increasing litter size in a sheep breed by marker-assisted selection of BMPR1B
A746G mutation.
PMID- 25846889
TI - Genomewide association study of body weight traits in Baluchi sheep.
PMID- 25846890
TI - Importance of molecular diagnosis in the accurate diagnosis of systemic carnitine
deficiency.
PMID- 25846891
TI - Diverse expression of sucrose transporter gene family in Zea mays.
PMID- 25846892
TI - A comparison of biological and cultural evolution.
AB - This review begins with a definition of biological evolution and a description of
its general principles. This is followed by a presentation of the biological
basis of culture, specifically the concept of social selection. Further,
conditions for cultural evolution are proposed, including a suggestion for
language being the cultural replicator corresponding to the concept of the gene
in biological evolution. Principles of cultural evolution are put forward and
compared to the principles of biological evolution. Special emphasis is laid on
the principle of selection in cultural evolution, including presentation of the
concept of cultural fitness. The importance of language as a necessary condition
for cultural evolution is stressed. Subsequently, prime differences between
biological and cultural evolution are presented, followed by a discussion on
interaction of our genome and our culture. The review aims at contributing to the
present discussion concerning the modern development of the general theory of
evolution, for example by giving a tentative formulation of the necessary and
sufficient conditions for cultural evolution, and proposing that human creativity
and mind reading or theory of mind are motors specific for it. The paper ends
with the notion of the still ongoing coevolution of genes and culture.
PMID- 25846893
TI - Induction of antigen-specific cytotoxic T lymphocytes by fusion cells generated
from allogeneic plasmacytoid dendritic and tumor cells.
PMID- 25846894
TI - (Pseudo)hemidystonia associated with anti-glutamic acid decarboxylase antibodies-
a case report.
PMID- 25846895
TI - A familial interstitial 4q35 deletion with no discernible clinical effects.
AB - Small deletions on the long arm of distal chromosome 4 do not appear to result in
gross congenital malformations, with the most frequently reported clinical
findings including mild to moderate intellectual disability, learning
disabilities and minor dysmorphic features. Here we report on a cytogenetically
detectable familial interstitial chromosome 4 long arm deletion with no
discernible phenotypic effects in a mother and her two daughters. The karyotypes
of the mother and her two daughters were: 46,XX,del(4)(q35.1q35.2). Based on the
results of FISH analyses using whole chromosome specific and subtelomeric probes,
the karyotype was designated as: 46,XX,del(4)(q35.1q35.2). ish del(4)(q35
qter)(WCP4+, 36P21+, dJ963K6-). Array-CGH analysis showed an interstitial
deletion encompassing 5.75 Mb in the 4q35.1-q35.2 genomic region
(chr4:184,717,878-190,469,337; hg19). This is the first report on a
cytogenetically detectable familial interstitial chromosome 4 long arm deletion
in which there are no discernible phenotypic effects. Both our findings and a
review of the literature suggest that more detailed molecular analyses are needed
in cases with distal chromosome 4 long arm deletions especially those with
breakpoints in the 4q35 region to establish a more precise genotype-phenotype
correlation.
PMID- 25846896
TI - Halochromic and hydrochromic squaric acid functionalized perylene bisimide.
AB - The functionalization of perylene bisimide by squaric acid afforded halochromic
dyes with pronounced acidity. The dye senses solvent polarity, pH and humidity by
means of pronounced changes in absorption spectra and thin film color through the
intramolecular charge transfer between perylene and cyclobutene cores initiated
by protonation/deprotonation.
PMID- 25846897
TI - Comprehensive 3-year study of the phenolic profile of Moroccan monovarietal
virgin olive oils from the Meknes region.
AB - The phenolic fraction of monovarietal virgin olive oils (VOOs) from the main
Moroccan cultivar Picholine marocaine (142 samples from three different subareas
of the Meknes region) was studied over three consecutive crop seasons (2011,
2012, and 2013) using a powerful LC-MS methodology. First, LC-ESI-TOF MS was used
to get a comprehensive characterization of the phenolic fraction; afterward, LC
ESI-IT MS was utilized for further identification (MS/MS experiments) and
quantitation purposes. A total of 28 phenolic compounds (and quinic acid) were
determined, revealing the complex profile of Meknes VOO, composed, in order of
abundance, by secoiridoids, phenolic alcohols, lignans, flavonoids, and phenolic
acids. Tukey's test was applied to ascertain possible significant intraregional
and/or interannual variations of the phenolic content of the Meknes VOOs under
study. Results showed that the content of phenolic compounds was mainly related
to the crop season.
PMID- 25846898
TI - An interlaboratory comparison program on ELF electric and magnetic fields
measurements performed in Greece: Second round of the scheme.
AB - The second round of an interlaboratory comparison program for extremely low
frequency electric and magnetic fields measurements was performed at the High
Voltage Laboratory of the National Technical University of Athens (Greece). The
16 participating laboratories measured the following: (i) electric field produced
by a scale transmission line; (ii) magnetic field produced by a medium voltage
cable; and (iii) magnetic field and frequency at the center of a standard square
coil and their delivered results were evaluated in all measurement scenarios with
use of performance statistics z-scores. Deviations between z-scores based on
usual estimators (mean value, standard deviation) and robust estimators (derived
with the robust algorithm described by the International Organization for
Standardization [ISO, 2005]) highlight improved performance of the robust
algorithm. An overall comparison to measurement procedure and performance results
of the first round proves effectiveness and necessity of the scheme. Improper
instrumentation or calibration, instability of the field source and measurement
position uncertainty are factors that may cause unsatisfactory performance of the
participants.
PMID- 25846899
TI - Progressive fat necrosis after breast augmentation with autologous lipotransfer:
a cause of long-lasting high Fever and axillary lymph node enlargement.
AB - Breast augmentation with autologous fat transfer has been widely practiced.
However, this procedure is not exempt from complications even after technique
refinement. This article aims to describe a case of long-lasting high fever,
axillary node enlargement, and upper extremity dysfunction caused by liponecrosis
after breast fat injection. Radiological and histological examination confirmed
liponecrosis in bilateral breasts. Aspiration, drainage, and irrigation were
performed along with empirical antibiotic treatment. The patient has made a full
recovery from the operation. Liponecrosis, one of the complications after
autologous fat grafting to the breast, may present widely different symptoms and
signs. Even experienced surgeons should not underestimate it and caution should
be used to maintain safety during and after the procedure. LEVEL OF EVIDENCE V:
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- 25846900
TI - Hospitalisations from 1 to 6 years of age: effects of gestational age and severe
neonatal morbidity.
AB - BACKGROUND: To investigate whether the adverse infant health outcomes associated
with early birth and severe neonatal morbidity (SNM) persist beyond the first
year of life and impact on paediatric hospitalisations for children up to 6 years
of age. METHODS: The study population included all singleton live births, >32
weeks gestation in New South Wales, Australia, in 2001-2005, with follow-up to 6
years of age. Birth data were probabilistically linked to hospitalisation data (n
= 392 964). The odds of hospitalisation, mean hospital length of stay (LOS) and
costs, and cumulative LOS were evaluated by gestational age and SNM using
multivariable analyses. RESULTS: A total of 74 341 (18.9%) and 41 404 (10.5%)
infants were hospitalised once and more than once, respectively. SNM was
associated with increased odds of hospitalisation once (adjusted odds ratio [aOR]
1.16 [95% confidence interval 1.10, 1.22]) and more than once [aOR 1.51 (1.43,
1.61)]. Decreasing gestational age was associated with increasing odds of
hospitalisation more than once from aOR 1.19 at 37-38 weeks to 1.49 at 33-34
weeks. Average LOS and costs per hospital admission were increased with SNM but
not with decreasing gestational age. Cumulative LOS was significantly increased
with SNM and decreasing gestational age. CONCLUSIONS: Adverse effects of SNM and
early birth persist between 1 and 6 years of age. Strategies to prevent early
birth and reduce SNM, and to increase health monitoring of vulnerable infants
throughout childhood may help reduce paediatric hospitalisations.
PMID- 25846901
TI - Rocket launcher: A novel reduction technique for posterior hip dislocations and
review of current literature.
AB - OBJECTIVE: We provide a review of literature on reduction techniques for
posterior hip dislocations and present our experience with a novel technique for
the reduction of acute posterior hip dislocations in the ED, 'the rocket
launcher' technique. METHODS: We present our results with six patients with
prosthetic posterior hip dislocation treated in our rural ED. We recorded patient
demographics. The technique involves placing the patient's knee over the
shoulder, and holding the lower leg like a 'Rocket Launcher' allow the
physician's shoulder to work as a fulcrum, in an ergonomically friendly manner
for the reducer. We used Fisher's t-test for cohort analysis between reduction
techniques. RESULTS: Of our patients, the mean age was 74 years (range 66 to 85
years). We had a 83% success rate. The one patient who the 'rocket launcher'
failed in, was a hemi-arthroplasty patient who also failed all other closed
techniques and needed open reduction. When compared with Allis (62% success
rate), Whistler (60% success rate) and Captain Morgan (92% success rate)
techniques, there was no statistically significant difference in the
successfulness of the reduction techniques. There were no neurovascular or
periprosthetic complications. CONCLUSION: We have described a reduction technique
for posterior hip dislocations. Placing the patient's knee over the shoulder, and
holding the lower leg like a 'Rocket Launcher' allow the physician's shoulder to
work as a fulcrum, thus mechanically and ergonomically superior to standard
techniques.
PMID- 25846902
TI - Membrane glucocorticoid receptors are localised in the extracellular matrix and
signal through the MAPK pathway in mammalian skeletal muscle fibres.
AB - KEY POINTS: Many studies have previously suggested the existence of stress
hormone receptors on the cell membrane of many cell types, including skeletal
muscle fibres; however, the exact localisation of these receptors and how they
signal to the rest of the cell is poorly understood. In this study, we
investigated the localisation and the mechanism(s) underlying the physiological
functions of these receptors in mouse skeletal muscle cells. We found that the
receptors were present throughout muscle development and that, in adult muscle
fibres, they were localised in the extracellular matrix, satellite cells (muscle
stem cells) and close to mitochondria. We also found that they signalled to the
rest of the cell by activating enzymes called mitogen-activated protein kinases.
From these results we suggest that, at physiological concentrations, stress
hormones may be important in skeletal muscle differentiation, repair and
regeneration. ABSTRACT: A number of studies have previously proposed the
existence of glucocorticoid receptors on the plasma membrane of many cell types,
including skeletal muscle fibres. However, their exact localisation and the
cellular signalling pathway(s) they utilise to communicate with the rest of the
cell are still poorly understood. In this study, we investigated the localisation
and the mechanism(s) underlying the non-genomic physiological functions of these
receptors in mouse skeletal muscle cells. The results show that the receptors
were localised in the cytoplasm in myoblasts, in the nucleus in myotubes, in the
extracellular matrix, in satellite cells and in the proximity of mitochondria in
adult muscle fibres. Also, they bound laminin in a glucocorticoid-dependent
manner. Treating small skeletal muscle fibre bundles with the synthetic
glucocorticoid beclomethasone dipropionate increased the phosphorylation (=
activation) of extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal
kinase and p38 mitogen-activated protein kinase. This occurred within 5 min and
depended on the fibre type and the duration of the treatment. It was also
abolished by the glucocorticoid receptor inhibitor, mifepristone, and a
monoclonal antibody against the receptor. From these results we conclude that the
non-genomic/non-canonical physiological functions of glucocorticoids, in adult
skeletal muscle fibres, are mediated by a glucocorticoid receptor localised in
the extracellular matrix, in satellite cells and close to mitochondria, and
involve activation of the mitogen-activated protein kinase pathway.
PMID- 25846903
TI - Clinical and procedural impact of aortic arch anatomic variants in carotid
stenting procedures.
AB - OBJECTIVES: To evaluate the impact of aortic arch variants in patients undergoing
carotid artery stenting (CAS). BACKGROUND: CAS is increasingly carried out to
treat the patients with internal carotid artery (ICA) stenosis. Aortic arch
anatomy may influence its feasibility and affect clinical outcome. METHODS:
Aortic arch digital subtraction angiography was systematically performed before
CAS. Aortic arch elongation and bovine arch variants were recorded. Catheter
manipulation time (CMT) was assessed for each patient. Adverse cardiovascular and
cerebral events were assessed at 30 days. RESULTS: A total of 282 consecutive
patients undergoing CAS under proximal balloon occlusion (57.8%) or distal filter
(42.2%) neuroprotection were enrolled (age, 72 +/- 7 years; 72.7% males). Type II
and III elongation variants were detected in 23.4% and 10.6% of patients,
respectively; in total, 20.5% of the patients had bovine configuration. CMT was
significantly influenced by aortic elongation (56.1 +/- 16.5 min in patients with
type III aortic arch configuration compared to 38.2 +/- 11.6 min in patients with
type I or type II, P < 0.01) and (in left ICA) by bovine configuration (49.2 +/-
11.4 min in bovine variants vs. 37.7 +/- 11.5 min in patients with nonbovine
anatomy, P < 0.001). CMT, but not aortic arch anatomy, resulted the only
independent predictor of 30-day adverse outcome (hazard ratio [HR], 1.07; 95%
confidence interval [CI], 1.03-1.10, P < 0.01). CONCLUSIONS: Adverse aortic arch
anatomies are frequently encountered in CAS procedures and are associated to
longer procedural times. A longer CMT increases the risk for adverse outcome.
These data suggest that a careful procedure planning aimed at a reduction of CMT
may be pivotal to improve the safety of CAS procedures.
PMID- 25846904
TI - Medication use and predictors of sexual activity in men and women with CVD.
AB - PURPOSE: To examine the influence of cardiac and noncardiac medications on sexual
activity by drug classification and generation of the drug, among men and women
with cardiovascular disease. DATA SOURCES: This study was a subanalysis (n = 224)
of survey data from a cross-sectional sample of 336 cardiac patients. Self
reported medications were categorized by generic drug name, classification, and
subclass and/or generation of the drug. Sexual activity was the presence or
absence of current sexual activity in the last 2 months. CONCLUSIONS: Patients
taking generation one beta blockers, particularly men; diuretics as a class; and
loop diuretics, were significantly less likely to be sexually active, with
diuretics negatively influencing sexual activity in women, but not men. Certain
antidepressant medications positively influenced sexual function, particularly
for women. Nearly 20% of the variances in sexual activity were explained by
younger age, fewer number of medications, higher education, and having a sexual
partner. IMPLICATIONS FOR PRACTICE: A new finding meriting further study was that
loop diuretics negatively impacted sexual activity, particularly for women; and
further studies of women overall are clearly needed. Advance practice nurses play
an important role in evaluating medications, proactively choosing drugs within a
class or subclass less likely to cause sexual problems, and in promoting sexual
quality of life of cardiac patients.
PMID- 25846905
TI - Lowering the B1 threshold for improved BEAR B1 mapping.
AB - PURPOSE: Accurate measurement of the nonuniform transmit radiofrequency field is
necessary for magnetic resonance imaging applications. The radiofrequency field
excitation amplitude (B1) is often obtained by acquiring a B1 map. We modify the
B1 estimation using adiabatic refocusing (BEAR) method to extend its range to
lower B1 magnitudes. THEORY AND METHODS: The BEAR method is a phase-based B1
mapping method, wherein hyperbolic secant pulses induce a phase sensitivity to
B1. The measurable B1 range is limited due to the adiabatic threshold of the
pulses. We redesign the method to use flattened hyperbolic secant pulses, which
have lower adiabatic thresholds. We optimize the flattened hyperbolic secant
parameters to minimize phase sensitivity to frequency variations. RESULTS: We
validate the performance of the new method via simulation and in vivo at 3T, and
show that for n <= 8, accurate B1 maps can be acquired using reduced nominal peak
B1 values. CONCLUSION: The adiabatic threshold for the BEAR method is reduced
with flattened hyperbolic secant pulses, which are optimized for accurate phase
to-B1 mapping over a frequency range, and allow for lower nominal B1 values. At
3T, the nominal B1 is decreased by 52% and the sensitivity to B1 is increased by
a factor of 3.8. This can improve the method's applicability for measurement of
low B1.
PMID- 25846906
TI - Olfactory function in Parkinson's Disease - effects of training.
AB - BACKGROUND: Up to 90% of patients with Parkinson's disease (PD) exhibit olfactory
dysfunction, but little is known about the effects of olfactory training. The
study aim was to investigate whether the ability to identify olfactory stimuli
can be improved by means of a brief training session. Furthermore, the impact of
hyposmia on quality of life in PD was investigated by means of a questionnaire.
METHODS: Olfactory function was rated in 34 patients with PD and in 26 controls
before and after a training session. An additional 20 patients with PD served as
a control group and were tested twice without an intervening training session.
Long-term effects were evaluated in a small subset of patients. Cognitive tests
and DaT SPECT scans were performed. RESULTS: We demonstrated significant same-day
and long-term training effects in trained PD patients compared with non-trained
PD patients. A slightly significant correlation was seen between the training
effect and DaT putamen values, but not with cognitive test scores. Furthermore,
patients with PD reported that hyposmia significantly decreased their quality of
life. CONCLUSIONS: Patients with PD improved the number of correctly identified
odors in an olfactory test through a brief training session. Olfactory training
may have potential in rehabilitation of patients with PD.
PMID- 25846907
TI - Visual and Vestibular Induced Eye Movements in Verbal Children and Adults with
Autism.
AB - This study assessed the functionality of vestibular, pursuit, and saccade
circuitry in autism across a wide age range. Subjects were 79 individuals with
autism (AUT) and 62 controls (CON) aged 5 to 52 years with IQ scores > 70. For
vestibular testing, earth-vertical axis rotation was performed in darkness and in
a lighted visual surround with a fixation target. Ocular motor testing included
assessment of horizontal saccades and horizontal smooth pursuit. No between-group
differences were found in vestibular reflexes or in mean saccade velocity or
accuracy. Saccade latency was increased in the AUT group with significant age
related effects in the 8-18 year old subgroups. There was a trend toward
decreased pursuit gain without age effects. Normal vestibular-induced eye
movements and normal saccade accuracy and velocity provide the most substantial
evidence to date of the functional integrity of brainstem and cerebellar pathways
in autism, suggesting that the histopathological abnormalities described in these
structures may not be associated with intrinsic dysfunction but rather reflect
developmental alterations related to forebrain cortical systems formation.
Increased saccade latency with age effects adds to the extensive existing
evidence of altered function and maturation of cortical systems in autism.
PMID- 25846908
TI - The efficacy of amrubicin on central nervous system metastases originating from
small-cell lung cancer: a case series of eight patients.
AB - BACKGROUND: Central nervous system (CNS) metastases caused by small-cell lung
cancer (SCLC) are incurable and therefore fatal. Although such metastases are
usually treated with chemotherapy or radiotherapy, their sensitivity to these
treatment measures is unclear. Amrubicin appears to be a promising agent for
relapsed SCLC, but its effectiveness in CNS metastases originating from SCLC is
unknown. METHODS: Between April 2002 and December 2009, 110 SCLC patients with
CNS metastasis were treated at Shizuoka Cancer Center. Of these, we
retrospectively reviewed 8 consecutive cases with CNS metastases originating from
relapsed SCLC that were treated with amrubicin as a second-line therapy. RESULTS:
We recorded three sensitive relapses and five refractory cases. Amrubicin yielded
a CNS response rate of 50 % (2 partial responses and 2 complete response; 95 %
CI, 21.5-78.5? %) and the disease control rate for CNS lesions was 87.5 % (95 %
CI, 52.9-97.8 %). All of the sensitive relapse patients achieved a partial
response. The median time to progression for CNS metastases was 150.5 days (95 %
CI, 9-171 days), and the median survival time from the start of amrubicin
administration was 230.5 days (95 % CI, 89-619 days). We also report a dramatic
improvement in one patient's radiological result of intramedullary spinal cord
metastasis and alleviation of her symptoms following amrubicin monotherapy
including this case series. CONCLUSIONS: The results of this study suggest that
amrubicin is active in patients with CNS metastases originating from SCLC.
PMID- 25846909
TI - Microbiological quality of selected spices and herbs including the presence of
Cronobacter spp.
AB - The cultivation of spices and herbs in parts of the world characterized by warm
climate and high humidity provides excellent conditions for the development of
microorganisms, including the undesirable ones. The aim of this study was to
determine the microbiological quality of spices and herbs available on the Polish
market, considering the occurrence of Cronobacter species bacteria. Analyses
covered 60 samples of commercial spices and herbs, including 38 samples of dried
herbs (basil, bay leaves, thyme, oregano, tarragon, marjoram, dill, parsley,
rosemary, lovage) and 16 samples of seasoning blends as well as 6 samples of
spices seeds and fruits (pimento, black pepper, coriander). All samples were
tested for the total count of aerobic mesophilic bacteria (TAMB) and for the
presence of Cronobacter spp. In most of the samples of spices and herbs (60.0%),
the TAMB did not exceed 10(4) CFU/g, and the level regarded as unacceptable
(>10(6) CFU/g) was not identified in any of the samples. The presence of
Cronobacter spp. was demonstrated in 10 (16.7%) samples of the analyzed products,
however these were mainly samples of herbs (basil, tarragon, parsley) and one
sample of a seasoning blend (Provence herbs). The highest microbiological
contamination (TAMB) was found in samples of herbs (oregano, tarragon, basil) and
in ready seasoning blends, in 21.1% and 25.0% of which the total count of aerobic
mesophiles was in the range of 10(5)-10(6) CFU/g. In all samples of spices seeds
and fruits (coriander, black pepper and pimento), the total count of aerobic
bacteria reached <10(4) CFU/g. Results achieved in the study indicate good
hygienic conditions in the production process of spices and herbs available on
the Polish market. The study demonstrated also that dried spices and herbs may be
carriers of Cronobacter species bacteria, though their presence in not often
detected in products of this type.
PMID- 25846911
TI - Modelling the influence of temperature, water activity and sodium metabisulphite
on the growth and OTA production of Aspergillus carbonarius isolated from Greek
wine grapes.
AB - The purpose of the present study was to develop a modelling approach to quantify
the effect of temperature (15-38 degrees C), a(w) (0.88-0.98) and sodium
metabisulphite (NaMBS) concentration (0-200 mg L(-1)) on the growth and OTA
production of Aspergillus carbonarius on a Grape Juice based Medium (GJM). Growth
responses of the fungus were recorded over time in terms of colony diameter
changes, and fitted to the primary model of Baranyi and the estimated maximum
growth rates (MU(max)) and lag phases (lambda) were subsequently modelled as a
function of temperature, a(w) and NaMBS concentration using the cardinal values
model with inflection (CMI). Moreover, OTA production was measured during fungal
growth and modelled as a function of the same parameters through a quadratic
polynomial model. Results showed that NaMBS increased the lag phase of A.
carbonarius, particularly at 38 degrees C/0.98 a(w) and 38 degrees C/0.96 a(w),
as well as at lower a(w) levels regardless of temperature. In the lowest NaMBS
concentration (50 mg L(-1)) there was no inhibitory effect, while at higher
concentrations (100 and 150 mg L(-1)) fungal growth was delayed. No growth was
observed at 200 mg L(-1) of NaMBS irrespective of temperature and a(w) levels.
The optimum values for growth were found in the range 30-35 degrees C and 0.96
a(w), while for OTA production at 20 degrees C and 0.98 a(w). The developed
models were subjected to internal and external validation and presented
satisfactory performance as inferred by graphical plots and statistical indices
(bias and accuracy factors). The present study will complement the findings on
the ecophysiology of A. carbonarius using NaMBS as an inhibitory agent.
PMID- 25846910
TI - Activity of lysozyme on Lactobacillus hilgardii strains isolated from Port wine.
AB - This work evaluated the effect of lysozyme on lactobacilli isolated from Port
wine. Bacterial growth experiments were conducted in MRS/TJ medium and
inactivation studies were performed in phosphate buffer (KH2PO4), distilled water
and wine supplemented with different concentrations of lysozyme. The response of
bacteria to lysozyme was found to be highly strain dependent. Some strains of
Lactobacillus hilgardii together with Lactobacillus collinoides and Lactobacillus
fructivorans were found to be resistant to concentrations of lysozyme as high as
2000 mg/L. It was observed that among the L. hilgardii taxon the resistant
strains possess an S-layer coat. Apparently, the strains of L. collinoides and L.
fructivorans studied are also S-layer producers as suggested by the total protein
profile obtained by SDS-PAGE. Thus, the hypothetical protective role of the S
layer against the action of lysozyme was investigated. From the various
treatments used to remove the protein from the surface of the cells, the one
employing LiCl (5 M) was the most effective. LiCl pre-treated cells exposed to
lysozyme (2000 mg/L) in KH2PO4 buffer maintained its resistance. However, when
cells were suspended in distilled water an increased sensitivity to lysozyme was
observed. Moreover, it was found that the addition of ethanol (20% v/v) to the
suspension medium (distilled water) triggered a strong inactivation effect
especially on cells previously treated with LiCl (reduction of >6 CFU log
cycles). The results suggest that the S-layer exerts a protective effect against
lysozyme and that the cell suspension medium influences the bacteriolysis
efficiency. It was also noted that ethanol enhances the inactivation effect of
lysozyme.
PMID- 25846912
TI - The microbial diversity of an industrially produced lambic beer shares members of
a traditionally produced one and reveals a core microbiota for lambic beer
fermentation.
AB - The microbiota involved in lambic beer fermentations in an industrial brewery in
West-Flanders, Belgium, was determined through culture-dependent and culture
independent techniques. More than 1300 bacterial and yeast isolates from 13
samples collected during a one-year fermentation process were identified using
matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
followed by sequence analysis of rRNA and various protein-encoding genes. The
bacterial and yeast communities of the same samples were further analyzed using
denaturing gradient gel electrophoresis of PCR-amplified V3 regions of the 16S
rRNA genes and D1/D2 regions of the 26S rRNA genes, respectively. In contrast to
traditional lambic beer fermentations, there was no Enterobacteriaceae phase and
a larger variety of acetic acid bacteria were found in industrial lambic beer
fermentations. Like in traditional lambic beer fermentations, Saccharomyces
cerevisiae, Saccharomyces pastorianus, Dekkera bruxellensis and Pediococcus
damnosus were the microorganisms responsible for the main fermentation and
maturation phases. These microorganisms originated most probably from the wood of
the casks and were considered as the core microbiota of lambic beer
fermentations.
PMID- 25846913
TI - Management of Listeria monocytogenes in fermented sausages using the Food Safety
Objective concept underpinned by stochastic modeling and meta-analysis.
AB - In the present work, a demonstration is made on how the risk from the presence of
Listeria monocytogenes in fermented sausages can be managed using the concept of
Food Safety Objective (FSO) aided by stochastic modeling (Bayesian analysis and
Monte Carlo simulation) and meta-analysis. For this purpose, the ICMSF equation
was used, which combines the initial level (H0) of the hazard and its subsequent
reduction (SigmaR) and/or increase (SigmaI) along the production chain. Each
element of the equation was described by a distribution to investigate the effect
not only of the level of the hazard, but also the effect of the accompanying
variability. The distribution of each element was determined by Bayesian modeling
(H0) and meta-analysis (SigmaR and SigmaI). The output was a normal distribution
N(-5.36, 2.56) (log cfu/g) from which the percentage of the non-conforming
products, i.e. the fraction above the FSO of 2 log cfu/g, was estimated at
0.202%. Different control measures were examined such as lowering initial L.
monocytogenes level and inclusion of an additional killing step along the process
resulting in reduction of the non-conforming products from 0.195% to 0.003% based
on the mean and/or square-root change of the normal distribution, and 0.001%,
respectively.
PMID- 25846914
TI - Microbial biofilms in seafood: a food-hygiene challenge.
AB - Seafood forms a part of a healthy diet. However, seafood can be contaminated with
foodborne pathogens, resulting in disease outbreaks. Because people consume large
amounts of seafood, such disease outbreaks are increasing worldwide. Seafood
contamination is largely due to the naturally occurring phenomenon of biofilm
formation. The common seafood bacterial pathogens that form biofilms are Vibrio
spp., Aeromonas hydrophila, Salmonella spp., and Listeria monocytogenes. As these
organisms pose a global health threat, recent research has focused on elucidating
methods to eliminate these biofilm-forming bacteria from seafood, thereby
improving food hygiene. Therefore, we highlight recent advances in our
understanding of the underlying molecular mechanisms of biofilm formation, the
factors that regulate biofilm development and the role of quorum sensing and
biofilm formation in the virulence of foodborne pathogens. Currently, several
novel methods have been successfully developed for controlling biofilms present
in seafood. In this review, we also discuss the epidemiology of seafood-related
diseases and the novel methods that could be used for future control of biofilm
formation in seafood.
PMID- 25846915
TI - Fermentation profile of green Spanish-style Manzanilla olives according to NaCl
content in brine.
AB - This work studies the effects of the partial substitution of NaCl with potassium
and calcium chloride salts on the fermentation profile of Spanish-style green
Manzanilla olives. For this purpose, response surface methodology based in an
enlarged simplex centroid mixture design with constrain (?salts = 100 g/L) was
used. Regarding to physicochemical characteristics, pH decreased when CaCl2
increased, titratable acidity was lower in presence of KCl while combined acidity
increased as the contents of KCl and CaCl2 were close to the barycentre of the
experiment (~33.33% each salt). Regarding to microbiological profile,
Enterobacteriaceae growth was slight stimulated in presence of high CaCl2
contents, yeast patterns were not linked to the initial brine compositions, while
the maximum lactic acid bacteria population decreased slightly as KCl and CaCl2
increased in the proportion 1:1, although a moderate (equilibrated) content of
both may be stimulating. Results obtained in this work show that Spanish-style
green Manzanilla cv. can be fermented in diverse mixtures of chloride salts,
albeit the initial CaCl2 should be limited to 20-30 g/L to prevent excessive
Enterobacteriaceae growth; combining it with a similar proportion of KCl may also
improve LAB predominance.
PMID- 25846916
TI - Potential of Lactobacillus curvatus LFC1 to produce slits in Cheddar cheese.
AB - Defects in Cheddar cheese resulting from undesired gas production are a sporadic
problem that results in significant financial losses in the cheese industry. In
this study, we evaluate the potential of a facultatively heterofermentative
lactobacilli, Lactobacillus curvatus LFC1, to produce slits, a gas related defect
in Cheddar cheese. The addition of Lb. curvatus LFC1 to cheese milk at log 3
CFU/ml resulted in the development of small slits during the first month of
ripening. Chemical analyses indicated that the LFC1 containing cheeses had less
galactose and higher levels of lactate and acetate than the control cheeses. The
composition the cheese microbiota was examined through a combination of two
culture independent approaches, 16S rRNA marker gene sequencing and automated
ribosomal intergenic spacer analysis; the results indicated that no known gas
producers were present and that high levels of LFC1 was the only significant
difference between the cheese microbiotas. A ripening cheese model system was
utilized to examine the metabolism of LFC1 under conditions similar to those
present in cheeses that exhibited the slit defect. The combined cheese and model
system results indicate that when Lb. curvatus LFC1 was added to the cheese milk
at log 3 CFU/ml it metabolized galactose to lactate, acetate, and CO2. For
production of sufficient CO2 to result in the formation of slits there needs to
be sufficient galactose and Lb. curvatus LFC1 present in the cheese matrix. To
our knowledge, facultatively heterofermentative lactobacilli have not previously
been demonstrated to result in gas-related cheese defects.
PMID- 25846917
TI - Inactivation and potential reactivation of pathogenic Escherichia coli O157:H7 in
bovine milk exposed to three monochromatic ultraviolet UVC lights.
AB - The ultraviolet (UVC) light irradiation has been recently studied as a novel non
thermal treatment method for milk. However, the potential reactivation of
microorganisms following exposure to UVC light in milk medium was not studied
yet. Therefore, the present study was conducted to determine the inactivation and
reactivation of pathogenic Escherichia coli O157:H7 following exposure to UV
light at three monochromatic wavelengths (222, 254 and 282 nm) in bovine milk.
The results showed that inactivation of E. coli O157:H7 following exposure to the
UV light at 254 nm was higher (P < 0.05) than that following exposure at 222 and
282 nm at the same UV fluence of 5, 10 and 20 mJ/cm(2). The reactivation of E.
coli O157:H7 was increased as the incubation time and temperature increased
regardless of the UV light sources under dark incubation phases. The evaluated
reactivation ratios of E. coli O157:H7 following exposure to the UV light at 254
nm in milk were lower (P < 0.05) than that following exposure at 222 nm after 1
to 6, 2 to 5 and 5-6 h incubation at 4, 20 and 37 degrees C, respectively.
Furthermore, at most incubation time points, the reactivation ratio of E. coli
O157:H7 following exposure to these three UV light sources were lower (P < 0.05)
than that of non-UV treated cells regardless of the incubation temperature. The
lowest reactivation ratios of E. coli O157:H7 were observed after milk exposure
to the UV light at 254 nm at 4 degrees C incubation when compared to that
following exposure to the UV light at 222 and 282 nm.
PMID- 25846918
TI - Genomic diversity of Oenococcus oeni populations from Castilla La Mancha and La
Rioja Tempranillo red wines.
AB - The Oenococcus oeni populations of Tempranillo wines from Castilla La Mancha and
La Rioja winemaking regions were analysed from one to three years and up to ten
wineries. The objective was to evaluate the genetic variability and the O. oeni
population structure. For this purpose a MLST scheme based on four loci (gyrB,
purK, pgm and recP genes) and PFGE with SfiI restriction enzyme were developed
for later combination. The results showed an O. oeni population completely
adapted to winemaking regions. A purifying selection influenced the genes
evolution, especially recP that along with purK were the most interesting loci to
analyse the genetic variability of the isolates. In this way linkage
disequilibrium and intergenic and intragenic recombination were determined
between isolates. PFGE typing with UPGMA data were not coincident with the
phylograms assessed for MLST by Maximum likelihood and combination of both
techniques differentiated all the isolates as strains. Those results led the
research to conclude that O. oeni population from CM and LR was a panmictic
population with a slight clonal evolution, so subpopulations could not be
described. A broader study including more winemaking regions with different grape
varieties and distinct ways of elaborating would be interesting to complete the
knowledge about O. oeni populations.
PMID- 25846919
TI - Targeting Fusarium graminearum control via polyamine enzyme inhibitors and
polyamine analogs.
AB - Fusarium graminearum not only reduces yield and seed quality but also constitutes
a risk to public or animal health owing to its ability to contaminate grains with
mycotoxins. Resistance problems are emerging and control strategies based on new
targets are needed. Polyamines have a key role in growth, development and
differentiation. In this work, the possibility of using polyamine metabolism as a
target to control F. graminearum has been assessed. It was found that putrescine
induces mycotoxin production, correlating with an over expression of TRI5 and
TRI6 genes. In addition, a homolog of the Saccharomyces cerevisiae TPO4 involved
in putrescine excretion was up-regulated as putrescine concentration increased
while DUR3 and SAM3 homologues, involved in putrescine uptake, were down
regulated. When 2.5 mM D, l-alpha-difluoromethylornithine (DFMO) was added to the
medium, DON production decreased from 3.2 to 0.06 ng/mm(2) of colony and growth
was lowered by up to 70 per cent. However, exogenous putrescine could overcome
DFMO effects. Five polyamine transport inhibitors were also tested against F.
graminearum. AMXT-1505 was able to completely inhibit in vitro growth and DON
production. Additionally, AMXT-1505 blocked F. graminearum growth in inoculated
wheat spikes reducing DON mycotoxin contamination from 76.87 MUg/g to 0.62 MUg/g.
PMID- 25846921
TI - Effect of ripeness stage during processing on Listeria monocytogenes growth on
fresh-cut 'Conference' pears.
AB - There are several factors that affect the shelf life of fresh-cut fruit,
including the cultivar, the ripeness stage of the fruit during processing and the
fruit's storage atmosphere and temperature. The effect of fruit ripeness during
processing on the survival and growth of Listeria monocytogenes on fresh-cut
'Conference' pear slices at different temperatures (5, 10 and 20 degrees C) was
studied. The four ripeness stages studied in this work (assessed by a fruit's
firmness) were mature-green (54-60 N), partially ripe (43-53 N), ripe (31-42 N)
and overripe (<31 N). In our studies, pH, acidity and soluble solids content did
not significantly change during conditioning at 20 degrees C. L. monocytogenes
grew under all experimental conditions, showing an increase of approximately 2
log CFU g(-1) after 8 days of storage at 5 degrees C. There were significant
differences in the L. monocytogenes population between different ripeness stages
at the end of the experiments at 10 and 20 degrees C. Regardless of the ripeness
stage of a fresh-cut pear, the growth potential of L. monocytogenes increased
with increasing temperature. A pear's ripeness stage during processing is an
important consideration to ensure the quality of a fresh-cut pear, but it is not
as important for preventing L. monocytogenes growth at common storage
temperatures.
PMID- 25846920
TI - Effect of sublethal preculturing on the survival of probiotics and metabolite
formation in set-yoghurt.
AB - The objective of this study was to investigate the effect of preculturing of
Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB12 under
sublethal stress conditions on their survival and metabolite formation in set
yoghurt. Prior to co-cultivation with yoghurt starters in milk, the two probiotic
strains were precultured under sublethal stress conditions (combinations of
elevated NaCl and low pH) in a batch fermentor. The activity of sublethally
precultured probiotics was evaluated during fermentation and refrigerated storage
by monitoring bacterial population dynamics, milk acidification and changes in
volatile and non-volatile metabolite profiles of set-yoghurt. The results
demonstrated adaptive stress responses of the two probiotic strains resulting in
their viability improvement without adverse influence on milk acidification. A
complementary metabolomic approach using SPME-GC/MS and (1)H-NMR resulted in the
identification of 35 volatiles and 43 non-volatile polar metabolites,
respectively. Principal component analysis revealed substantial impact of the
activity of sublethally precultured probiotics on metabolite formation
demonstrated by distinctive volatile and non-volatile metabolite profiles of set
yoghurt. Changes in relative abundance of various aroma compounds suggest that
incorporation of stress-adapted probiotics considerably influences the
organoleptic quality of product. This study provides new information on the
application of stress-adapted probiotics in an actual food-carrier environment.
PMID- 25846922
TI - Bacteria and yeast microbiota in milk kefir grains from different Italian
regions.
AB - Kefir grains are a unique symbiotic association of different microrganisms,
mainly lactic acid bacteria, yeasts and occasionally acetic acid bacteria,
cohabiting in a natural polysaccharide and a protein matrix. The microbial
composition of kefir grains can be considered as extremely variable since it is
strongly influenced by the geographical origin of the grains and by the sub
culturing method used. The aim of this study was to elucidate the bacteria and
yeast species occurring in milk kefir grains collected in some Italian regions by
combining the results of scanning electron microscopy analysis, viable counts on
selective culture media, PCR-DGGE and pyrosequencing. The main bacterial species
found was Lactobacillus kefiranofaciens while Dekkera anomala was the predominant
yeast. The presence of sub-dominant species ascribed to Streptococcus
thermophilus, Lactococcus lactis and Acetobacter genera was also highlighted. In
addition, Lc. lactis, Enterococcus sp., Bacillus sp., Acetobacter fabarum,
Acetobacter lovaniensis and Acetobacter orientalis were identified as part of the
cultivable community. This work further confirms both the importance of combining
culture-independent and culture-dependent approaches to study microbial diversity
in food and how the combination of multiple 16S rRNA gene targets strengthens
taxonomic identification using sequence-based identification approaches.
PMID- 25846923
TI - The combined efficacy of carvacrol and modified atmosphere packaging on the
survival of Salmonella, Campylobacter jejuni and lactic acid bacteria on turkey
breast cutlets.
AB - The primary objective of this study was to determine the efficacy of carvacrol in
combination with modified atmosphere packaging (MAP) in reducing Salmonella on
turkey breast cutlets stored at 4 degrees C. In experiment I, carvacrol (0.5, 1,
and 2% v/v) was applied as surface treatment and samples were stored under
aerobic condition or as surface and dip treatments followed by storage in an
environment of 100% carbon dioxide. The findings of the experiment I revealed the
synergistic activity of carvacrol with carbon dioxide in reducing Salmonella when
used as dip treatment compared to the surface treatment. In experiment II, turkey
breast cutlets were dip treated with carvacrol (0.25, 0.5, and 1% v/v) for 30 s
and stored under MAP (95% carbon dioxide and 5% oxygen) to evaluate the efficacy
against Salmonella, Campylobacter jejuni and lactic acid bacteria on turkey
breast cutlets. In experiment II, the combined application of carvacrol and MAP
resulted in 1.0-2.0 log CFU/g reduction (P <= 0.05) of both Salmonella and
Campylobacter on turkey breast cutlets for 7 d storage at 4 degrees C. MAP alone
and in combination with carvacrol reduced lactic acid bacteria (P <= 0.05) on
cutlets stored at 4 degrees C for 21 d period. There was no difference (P <=
0.05) in meat color among treatments and controls except for an increased
paleness of meat (P <= 0.05) observed for the 1% carvacrol treated cutlets stored
under MAP after 21 d of storage. The high concentration of carbon dioxide and
carvacrol treatments did not cause any alteration in meat pH (P <= 0.05). In
conclusion, carvacrol was effective at a low concentration of 0.25% (v/v) in
reducing Salmonella and C. jejuni by ~1.0 log CFU/g when stored under MAP.
PMID- 25846924
TI - Effect of salinity and incubation time of planktonic cells on biofilm formation,
motility, exoprotease production, and quorum sensing of Aeromonas hydrophila.
AB - The aim of this study was to determine the effect of salinity and age of cultures
on quorum sensing, exoprotease production, and biofilm formation by Aeromonas
hydrophila on stainless steel (SS) and crab shell as substrates. Biofilm
formation was assessed at various salinities, from fresh (0%) to saline water
(3.0%). For young and old cultures, planktonic cells were grown at 30 degrees C
for 24 h and 96 h, respectively. Biofilm formation was assessed on SS, glass, and
crab shell; viable counts were determined in R2A agar for SS and glass, but
Aeromonas-selective media was used for crab shell samples to eliminate bacterial
contamination. Exoprotease activity was assessed using a FluoroTM protease assay
kit. Quantification of acyl-homoserine lactone (AHL) was performed using the
bioreporter strain Chromobacterium violaceum CV026 and the concentration was
confirmed using high-performance liquid chromatography (HPLC). The concentration
of autoinducer-2 (AI-2) was determined with Vibrio harveyi BB170. The biofilm
structure at various salinities (0-3 %) was assessed using field emission
electron microscopy (FESEM). Young cultures of A. hydrophila grown at 0-0.25%
salinity showed gradual increasing of biofilm formation on SS, glass and crab
shell; swarming and swimming motility; exoproteases production, AHL and AI-2
quorum sensing; while all these phenotypic characters reduced from 0.5 to 3.0%
salinity. The FESEM images also showed that from 0 to 0.25% salinity stimulated
formation of three-dimensional biofilm structures that also broke through the
surface by utilizing the chitin surfaces of crab, while 3% salinity stimulated
attachment only for young cultures. However, in marked contrast, salinity (0.1
3%) had no effect on the stimulation of biofilm formation or on phenotypic
characters for old cultures. However, all concentrations reduced biofilm
formation, motility, protease production and quorum sensing for old culture.
Overall, 0-0.25% salinity enhanced biofilm formation and expression of quorum
sensing regulatory genes in young cultures, whereas these responses were reduced
when salinity was >0.25%. In old cultures, salinity at any concentrations (0.1
3%) induced stress in A. hydrophila. The present study provides insight into the
ecology of A. hydrophila growing on fish and crustaceans such as shrimp and crabs
in estuarine and seawater.
PMID- 25846925
TI - A novel microfluidic mixer-based approach for determining inactivation kinetics
of Escherichia coli O157:H7 in chlorine solutions.
AB - Determination of the minimum free chlorine concentration needed to prevent
pathogen survival/cross-contamination during produce washing is essential for the
development of science-based food safety regulations and practices. Although the
trend of chlorine concentration-contact time on pathogen inactivation is
generally understood, specific information on chlorine and the kinetics of
pathogen inactivation at less than 1.00 s is urgently needed by the produce
processing industry. However, conventional approaches to obtain this critical
data have been unable to adequately measure very rapid responses. This paper
reports our development, fabrication, and test of a novel microfluidic device,
and its application to obtain the necessary data on pathogen inactivation by free
chlorine in produce wash solution in times as short as 0.10 s. A novel
microfluidic mixer with the capability to accurately determine the reaction time
and control the chlorine concentration was designed with three inlets for
bacterial, chlorine and dechlorinating solutions, and one outlet for effluent
collection. The master mold was fabricated on a silicon wafer with microchannels
via photopolymerization. Polydimethylsiloxane replicas with patterned
microchannels were prototyped via soft lithography. The replicas were further
assembled into the micromixer on glass via O2 plasma treatment, and the inlets
were connected to a syringe pump for solution delivery. To determine the kinetics
of free chlorine on pathogen inactivation, chlorine solutions of varying
concentrations were first pumped into the micromixer, together with the addition
of bacterial suspension of Escherichia coli O157:H7 through a separate inlet.
This was followed by injection of dechlorinating solution to stop the chlorine
pathogen reaction. The effluent was collected and the surviving bacteria cells
were enumerated using a modified 'Most Probable Number' method. Free chlorine
concentration was determined using a standard colorimetric method. The contact
time was experimentally set by adjusting the solution flow rate, and was
estimated by computational fluid dynamics modeling. Results showed that 1)
pathogen inactivation was significantly affected by free chlorine concentration
(P < 0.0001) and subsecond reaction time (P < 0.0001) and their interactions (P <
0.0001); and 2) the current industry practice of using 1.0 mg/L free chlorine
will require more than 1.00 s total contact to achieve a 5-log10 reduction in an
E. coli O157:H7 population, whereas a 10.0 mg/L free chlorine solution will
achieve 5-log10 reduction in as little as 0.25 s. Information obtained from this
study will provide critical insight on kinetics of bacterial inactivation for a
broad range of sanitizers and produce wash operational conditions, thus
facilitating the development and implementation of science-based food safety
regulations and practices for improving food safety.
PMID- 25846926
TI - A five-year study on prevalence and antimicrobial resistance of Campylobacter
from poultry carcasses in Poland.
AB - During 2009-2013 a total of 2114 swab samples collected from broiler carcasses in
all 16 voivodeships (administrative districts) of Poland were examined for the
presence of Campylobacter jejuni and Campylobacter coli. The antimicrobial
resistance of the isolates to ciprofloxacin, tetracycline and erythromycin using
the MIC method was also tested. It was found that 1151 (54.4%) carcasses were
contaminated with Campylobacter, with 50% of C. jejuni and C. coli species
isolated from positive samples. The temporal trend in the prevalence of
Campylobacter-positive samples demonstrated that the highest percentage of
carcasses was contaminated during the first year of the survey (70.5%) whereas in
the last year (2013) only 36.3% of broilers contained these bacteria.
Antimicrobial resistance analysis showed that overall 939 (81.6%) of isolates
were resistant to ciprofloxacin, 646 (56.1%) to tetracycline but only 28 (2.4%)
to erythromycin. Significant differences in resistance profiles between C. jejuni
and C. coli were observed with greater resistance level observed in the latter
species. Furthermore, a significant increase in the percentage of C. jejuni
resistant to ciprofloxacin (from 59.6% in 2009 to 85.9% in 2014) and to
tetracycline (from 23.2% to 70.4%, respectively) was identified. Only 20 (1.7%)
Campylobacter isolates displayed a multiresistance pattern.
PMID- 25846927
TI - Synergistic antimicrobial activity of caprylic acid in combination with citric
acid against both Escherichia coli O157:H7 and indigenous microflora in carrot
juice.
AB - The identification of novel, effective, and non-thermal decontamination methods
is imperative for the preservation of unpasteurized and fresh vegetable juices.
The aim of this study was to examine the bactericidal effects of caprylic acid +
citric acid against the virulent pathogen Escherichia coli O157:H7 and the
endogenous microflora in unpasteurized fresh carrot juice. Carrot juice was
treated with either caprylic acid, citric acid, or a combination of caprylic acid
+ citric acid at mild heating temperature (45 degrees C or 50 degrees C). The
color of the treated carrot juice as well as microbial survival was examined over
time. Combined treatment was more effective than individual treatment in terms of
both color and microbial survival. Caprylic acid + citric acid treatment (each at
5.0 mM) at 50 degrees C for 5 min resulted in 7.46 and 3.07 log CFU/ml
reductions in the E. coli O157:H7 and endogenous microflora populations,
respectively. By contrast, there was no apparent reduction in either population
following individual treatment. A validation assay using a low-density E. coli
O157:H7 inoculum (3.31 log CFU/ml) showed that combined treatment with caprylic
acid (5.0 mM) + citric acid (2.5 mM) at 50 degrees C for >5 min or with caprylic
acid + citric acid (both at 5.0 mM) at either 45 degrees C or 50 degrees C for
>5 min completely destroyed the bacteria. Combined treatment also increased the
redness of the juice, which is a perceived indication of quality. Taken together,
these results indicate that combined treatment with low concentrations of
caprylic acid and citric acid, which are of biotic origin, can eliminate
microorganisms from unpasteurized carrot juice.
PMID- 25846928
TI - Assessment of microbial risk factors and impact of meteorological conditions
during production of baby spinach in the Southeast of Spain.
AB - There is a timely need to evaluate the effect agricultural factors and
meteorological conditions on fresh produce contamination. This study evaluated
those risk factors and described, for the first time, the distribution of
indicator microorganisms (Escherichia coli, Enterococcus, coliforms, and
Enterobacteriaceae) and the prevalence of foodborne pathogens (Enterohaemorrhagic
E. coli, Listeria monocytogenes and Salmonella spp.) in baby spinach grown in the
Southeast of Spain. A longitudinal study was conducted on three farms (2011
2013). Results obtained for E. coli highlighted soil and irrigation water as
important factors affecting the microbial safety of baby spinach. Significant
differences in the proportion of E. coli positive samples were found between
treated (46.1%) and untreated (100%) irrigation water. However, the microbial
quality of irrigation water didn't affect E. coli prevalence in produce. All E.
coli positive spinach samples were detected at the highest observed temperature
range suggesting that ambient temperature affects the probability and extent of
spinach contamination. Salmonella spp. was detected by RT-PCR in manure, soil,
irrigation water and baby spinach but only two of them (manure and irrigation
water) were confirmed by isolation in culture media. Salmonella RT-PCR positive
samples showed higher levels of E. coli than Salmonella negative samples. This
preliminary finding supports recent identification of E. coli as a suitable
parameter for the hygiene criterion at the primary production of leafy greens.
PMID- 25846929
TI - Microbiological and chemical characteristics of taruba, an indigenous beverage
produced from solid cassava fermentation.
AB - The aim of this work was to identify and characterize the microbiota present
during fermentation and in the final beverage, taruba, by culture-dependent and
independent methods. In addition, target chemical compounds (carbohydrates,
organic acids, and ethanol) were evaluated. Lactic acid bacteria (LAB) and
mesophilic bacteria were the predominant microorganisms. Among them,
Lactobacillus plantarum, Lactobacillus brevis, Leuconostoc mesenteroides, and
Bacillus subtilis were frequently isolated and detected by DGGE analysis.
Torulaspora delbrueckii was the dominant yeast species. Yeast isolates Pichia
exigua, Candida rugosa, T. delbrueckii, Candida tropicalis, Pichia kudriavzevii,
Wickerhamomyces anomalus, and Candida ethanolica and bacteria isolates Lb.
plantarum, Bacillus subtilis, Bacillus amyloliquefaciens, Bacillus licheniformis,
Bacillus sp., and Chitinophaga terrae showed amylolytic activity. Only isolates
of P. exigua and T. delbrueckii and all species of the genus Bacillus identified
in this work exhibited proteolytic activity. All microbial isolates grew at 38
degrees C, and only the isolates belonging to Hanseniaspora uvarum species did
not grow at 42 degrees C. These characteristics are important for further
development of starter cultures; isolates of T. delbrueckii, P. exigua, and
Bacillus species identified in this work displayed all of these properties and
are potential strains for use as starter culture in cassava fermented food.
PMID- 25846930
TI - Effect of sulfur dioxide fumigation on survival of foodborne pathogens on table
grapes under standard storage temperature.
AB - We examined the fate of Listeria monocytogenes, Escherichia coli O157:H7, and
Salmonella enterica Thompson inoculated on freshly-harvested table grapes under
standard cold storage with initial and weekly sulfur dioxide (SO2) fumigation. L.
monocytogenes and S. enterica Thompson were much more sensitive to cold
temperature than E. coli O157:H7. Furthermore, L. monocytogenes was highly
susceptible to SO2. Initial fumigation with 100 or 200 ppm-hr was sufficient to
eliminate this pathogen on grapes with low (10(4) cells/grape) and high (10(6)
cells/grape) inocula, respectively. Initial fumigation with 300 ppm-hr reduced S.
enterica Thompson population about 300- and 10-fold on grapes with low and high
inocula, respectively. Initial fumigation with 300 ppm-hr reduced E. coli O157:H7
population to less than 10-fold, regardless of inoculum density. When grapes were
inoculated with the high inoculum and fumigated on days 0 and 7 with 200 or 300
ppm-hr SO2, S. enterica Thompson and E. coli O157:H7 were completely inactivated
between days 8 and 14 of cold storage. Standard cold storage combined with SO2
fumigation was effective in reducing and eliminating all three pathogens on table
grapes, however, depending on the dose, two or three fumigations were needed for
elimination of S. enterica Thompson and E. coli O157:H7.
PMID- 25846931
TI - Effect of salt on cell viability and membrane integrity of Lactobacillus
acidophilus, Lactobacillus casei and Bifidobacterium longum as observed by flow
cytometry.
AB - The aim of the current study was to investigate the effect of varying sodium
chloride concentrations (0-5%) on viability and membrane integrity of three
probiotic bacteria, Lactobacillus acidophilus, Lactobacillus casei and
Bifidobacterium longum, using conventional technique and flow cytometry. Double
staining of cells by carboxyfluorescein diacetate (cFDA) and propidium iodide
(PI) enabled to evaluate the effect of NaCl on cell esterase activity and
membrane integrity. Observations from conventional culture technique were
compared with findings from flow cytometric analysis on the metabolic activities
of the cells and a correlation was observed between culturability and dye
extrusion ability of L. casei and B. longum. However, a certain population of L.
acidophilus was viable as per the plate count method but its efflux activity was
compromised. Esterase activity of most bacteria reduced significantly (P < 0.05)
during one week storage at NaCl concentrations greater than 3.5%. The study
revealed that L. casei was least affected by higher NaCl concentrations among the
three probiotic bacteria, as opposed to B. longum where the cF extrusion
performance was greatly reduced during 1 wk storage. The metabolic activity and
salt resistance of L. casei was found to be highest among the bacteria studied.
PMID- 25846932
TI - Survival of pathogenic enterohemorrhagic Escherichia coli (EHEC) and control with
calcium oxide in frozen meat products.
AB - This study investigated both the level of microbial contamination and the
presence of enterohemorrhagic Escherichia coli (EHEC) in frozen meat products,
followed by the evaluation of its survival over 180 days under frozen
temperature. We also examined the effect of calcium oxide on the populations of
EHEC, E. coli O157:H7 and EPEC under both 10 degrees C and -18 degrees C
storage conditions. Afterward, the morphological changes occurring in EHEC cells
in response to freezer storage temperature and calcium oxide (CaO) treatments
were examined using transmission electron microscopy. Among the frozen meat
products tested, the highest contamination levels of total aerobic counts,
coliforms and E. coli were observed in pork cutlets. Examination showed that 20%
of the frozen meat products contained virulence genes, including verotoxin (VT) 1
and 2. Over 180 days of frozen storage and after 3 freeze-thaw cycles, the
population of EHEC did not change regardless of the type of products or initial
inoculated concentration, indicating the strong survival ability of EHEC.
Subsequent testing revealed that the growth of three pathogenic E. coli strains
was completely inhibited in meat patties prepared with 1% CaO, stored at 10
degrees C. However, the addition of 2% CaO was necessary to control the survival
of EHEC, E. coli O157:H7 and EPEC in meat patties stored at -18 degrees C. CaO
reduced the population of E. coli O157:H7 more effectively than the other EHEC
and EPEC strains at both 10 degrees C and -18 degrees C. Transmission electron
microscopy analysis revealed that exposed EHEC cells were resistant to the
freezer storage temperature, although some cells incurred injury and death after
several freeze-thaw cycles. Most of the cells exposed to CaO were found to have
died or lost their cellular integrity and membranes, indicating that CaO has the
potential to be used as a powerful antimicrobial agent for manufacturing frozen
meat products.
PMID- 25846933
TI - Comparison of homo- and heterofermentative lactic acid bacteria for
implementation of fermented wheat bran in bread.
AB - Despite its potential health benefits, the integration of wheat bran into the
food sector is difficult due to several adverse technological and sensory
properties such as bitterness and grittiness. Sourdough fermentation is a
promising strategy to improve the sensory quality of bran without inducing severe
changes to the bran matrix. Therefore, identification of species/strains with
potential for industrial sourdough fermentations is important. We compared the
effects of different representatives of species of lactic acid bacteria (LAB) on
wheat bran. Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus
brevis, Lactobacillus sanfranciscensis and Fructobacillus fructosus produced
highly individual fermentation patterns as judged from carbohydrate consumption
and organic acid production. Interestingly, fructose was released during all bran
fermentations and possibly influenced the fermentation profiles of obligately
heterofermentative species to varying degrees. Except for the reduction of
ferulic acid by L. plantarum and L. pentosus, analyses of phenolic compounds and
alkylresorcinols suggested that only minor changes thereof were induced by the
LAB metabolism. Sensory analysis of breads baked with fermented bran did not
reveal significant differences regarding perceived bitterness and aftertaste. We
conclude that in addition to more traditionally used sourdough species such as L.
sanfranciscensis and L. brevis, also facultatively heterofermentative species
such as L. plantarum and L. pentosus possess potential for industrial wheat bran
fermentations and should be considered in further investigations.
PMID- 25846934
TI - Mathematical model for viral depuration kinetics in shellfish: an useful tool to
estimate the risk for the consumers.
AB - Enteric virus depuration from shellfish is a complex biological process that may
be influenced by biological properties of the mollusc and/or virus species. On
the basis of previous experimental data, a mathematical model was developed to
characterize the kinetics of viral elimination during the depuration process. The
experimental data consisted on twenty depuration trials, each with 60 kg of
Manila clams (Venerupis philippinarum) and mediterranean mussels (Mytilus
galloprovincialis) previously subjected to bioaccumulation with HAV or MNV-1 (as
a surrogate for human norovirus), that were performed in an experimental
depuration system during 7 days. It was observed that although viral loads decay
along depuration, a residual viral load remains at the end of the process
suggesting a decomposition of viral load in a diluted load (susceptible of
depuration) and a non-diluted load (unavailable to depurate). The model yielded a
general equation, which can predict the viral load at any depuration time knowing
the specific filtration rate, dependent on the bivalve species, and specific
viral properties. The mathematical model can be combined with quantitative risk
assessment calculations to determine the safety of the depurated shellfish, which
can be very helpful not only for shellfish producers but also to public health
authorities.
PMID- 25846935
TI - A gaseous acetic acid treatment to disinfect fenugreek seeds and black pepper
inoculated with pathogenic and spoilage bacteria.
AB - Contamination of spices by pathogenic and/or spoilage bacteria can be deleterious
to consumer's health and cause deterioration of foods, and inactivation of such
bacteria is necessary for the food industry. The present study examined the
effect of gaseous acetic acid treatment in reducing Escherichia coli O157:H7,
Salmonella Enteritidis and Bacillus subtilis populations inoculated on fenugreek
seeds and black pepper. Treatment with gaseous acetic acid at 0.3 mmol/L, 0.6
mmol/L and 4.7 mmol/L for 1-3 h significantly reduced the populations of E. coli
O157:H7 and Salmonella Enteritidis on black pepper and fenugreek seeds at 55
degrees C (p < 0.05). The gas treatments at 4.7 mmol/L were more effective in
inactivating the pathogens than the treatment at 0.3 mmol/L. An approximately 5.0
log reduction was obtained after 3 h of treatment with 4.7 mmol/L acetic acid. No
significant reductions in the population of B. subtilis spores inoculated on
fenugreek seeds and black pepper were obtained after the gas treatments at 0.3
mmol/L or 0.6 mmol/L (p > 0.05). However, the gas treatment at 4.7 mmol/L
significantly reduced B. subtilis spores (p < 0.05), and 4.0 log CFU/g and 3.5
log CFU/g reductions on fenugreek seeds and black pepper, respectively, were
obtained after 3 h of treatment.
PMID- 25846936
TI - Inactivation of Shiga toxin-producing Escherichia coli in lean ground beef by
gamma irradiation.
AB - In this study the radiation resistance of 40 Shiga Toxin-Producing Escherichia
coli (STEC) isolates which contained various combinations of the shiga toxin 1
(stx1), shiga toxin 2 (stx2), intimin (eae), and hemolysin (ehx) genes were
determined. The STEC were suspended in lean ground beef and irradiated at 4
degrees C. D10 values, the radiation dose needed to reduce 1 log (90%) of a
microorganism, ranged from 0.16 to 0.48 kGy, with a mean of 0.31 kGy for the 40
isolates. Isolates associated with illness outbreaks had a mean D10 of 0.27 kGy,
while non-outbreak isolates had a mean D10 of 0.36 kGy (p < 0.05). The presence
or absence of stx1, stx2, or both stx1 and 2 had no affect on D10 (p > 0.05). The
presence (0.30 kGy) or absence (0.35 kGy) of ehx had no affect on D10 (p > 0.05).
However, the mean D10 of isolates lacking eae (0.37 kGy) were significantly
higher than those containing eae (0.27 kGy) (p < 0.05). There was no difference
in D10 for isolates lacking eae regardless of whether or not they were associated
with a foodborne illness outbreak (p > 0.05). It may be possible to use some of
the STEC isolates which lacked eae, ehx, or both (D10 > 0.30) as avirulent
surrogates in food irradiation research. The data presented in this study
provides risk assessors data for metagenomic analysis as well as food and
radiation processors with valuable information to control of STEC in meat.
PMID- 25846937
TI - Intrapartum referral from primary to secondary care in the Netherlands: a
retrospective cohort study on management of labor and outcomes.
AB - BACKGROUND: In the Dutch maternity care system, primary care midwives provide
care to low-risk women and refer to obstetricians if risks or complications
occur. We examined reasons for referral, management of labor, and maternal and
neonatal outcomes among women who were referred during labor. METHODS: In a
retrospective cohort study, descriptive analyses were performed on data obtained
from patient records. Six purposively chosen hospitals in The Netherlands
participated in the study from June 2011 to February 2012. The study population
included 600 pregnant women who were referred during labor from primary to
secondary care. MAIN OUTCOME MEASURES: Reasons for referral, interventions after
referral, mode of delivery, and maternal and neonatal outcomes. RESULTS: Of women
who were referred during labor, three out of four women were referred for
moderate risk indications: request for pain relief (30.5%), meconium-stained
liquor (25.3%), failure to progress during first stage of labor (14.0%), and
prolonged ruptured membranes without contractions (12.5%). Of all women, 65.7
percent had a spontaneous vaginal delivery and 59.7 percent received some kind of
pain relief. Acute referral, meaning fetal distress, occurred in 5.5 percent. Of
the newborns, 2.7 percent had an Apgar score of 7 or less after 5 minutes and 1.2
percent had an umbilical cord pH < 7.05. Postpartum complications occurred among
11.0 percent of women. CONCLUSION: Women who are referred during labor have a
high probability of spontaneous vaginal delivery. To improve continuity of care
and satisfaction for this group of women, management of labor could be continued
by trained primary care midwives.
PMID- 25846938
TI - Outflow tract ventricular arrhythmias: An update.
AB - During the last 20 years, the molecular etiology for many ventricular
tachyarrhythmias once referred to as "idiopathic," has been elucidated. These
arrhythmias are due to mutations in ion channels or structural proteins and
include ventricular tachyarrhythmias due to long and short QT syndromes, Brugada
syndrome, and catecholaminergic polymorphic ventricular tachycardia (VT).
However, the basis for the most common form of idiopathic ventricular arrhythmia,
which originates from right or left ventricular outflow tracts, has remained
elusive. Although traditionally considered a benign ventricular arrhythmia, it is
now appreciated that some outflow tract arrhythmias also trigger polymorphic VT
or sudden cardiac death or result in cardiomyopathy. The current understanding of
outflow tract arrhythmias will be examined.
PMID- 25846939
TI - Understanding Sources of Knowledge for Coaches of Athletes with Intellectual
Disabilities.
AB - BACKGROUND: Recent research has investigated development of coaching knowledge;
however, less research has investigated the development of coaches who coach
athletes with intellectual disabilities. The purpose of this study was to
understand how coaches of athletes with intellectual disabilities gain their
knowledge. METHOD: Forty-five Special Olympics Canada coaches participated in
structured telephone interviews investigating actual and ideal sources of
coaching knowledge. Coaching knowledge was categorized across the dimensions of
competition, organization and training. RESULTS: Coaches primarily learned by
doing and by consulting with coaching peers. Information about ideal sources of
coaching knowledge demonstrates that coaches would value structured coaching
courses, learning from mentors and from administrative support, in addition to
learning on their own and from peers. DISCUSSION: Results suggest that a broader
approach to education should be incorporated into coaching athletes with
intellectual disabilities. Recommendations for achieving such goals are provided.
PMID- 25846940
TI - Coeliac disease - from genetic and immunological studies to clinical
applications.
AB - Coeliac disease is a common and important gastrointestinal disease. It affects at
least 1%, most Western European populations and in Nordic countries it is even
more frequent. It is strongly associated with certain Human Leukocyte Antigen-DQ
genes and triggered by ingestion of wheat gluten and related cereals from rye and
barley. The diagnosis relies on a combination of clinical signs, serology and
small intestinal biopsy. Work during the last couple of decades has shown that
gluten-specific, Human Leukocyte Antigen-DQ-restricted T-cells in the intestinal
mucosa are of paramount importance in the disease process. The gluten peptides
are chemically modified by the endogenous enzyme transglutaminase 2, the same
enzyme that serves as target in today's sensitive serological tests for coeliac
disease. The increasing knowledge on the disease process allows for development
of improved diagnosis, patient care and new treatment modalities.
PMID- 25846941
TI - Enzyme activities of Arabidopsis inositol polyphosphate kinases AtIPK2alpha and
AtIPK2beta are involved in pollen development, pollen tube guidance and
embryogenesis.
AB - Inositol polyphosphate kinase (IPK2) is a key component of inositol polyphosphate
signaling. There are two highly homologous inositol polyphosphate kinases
(AtIPK2alpha and AtIPK2beta) in Arabidopsis. Previous studies that overexpressed
or reduced the expression of AtIPK2alpha and AtIPK2beta revealed their roles in
auxiliary shoot branching, abiotic stress responses and root growth. Here, we
report that AtIPK2alpha and AtIPK2beta act redundantly during pollen development,
pollen tube guidance and embryogenesis. Single knock-out mutants of atipk2alpha
and atipk2beta were indistinguishable from the wild type, whereas the atipk2alpha
atipk2beta double mutant could not be obtained. Detailed genetic and cytological
investigations showed that the mutation of AtIPK2alpha and AtIPK2beta resulted in
severely reduced transmission of male gametophyte as a result of abnormal pollen
development and defective pollen tube guidance. In addition, the early embryo
development of the atipk2alpha atipk2beta double mutant was also aborted.
Expressing either catalytically inactive or substrate specificity-altered
variants of AtIPK2beta could not rescue the male gametophyte and embryogenesis
defects of the atipk2alpha atipk2beta double mutant, implying that the kinase
activity of AtIPK2 is required for pollen development, pollen tube guidance and
embryogenesis. Taken together, our results provide genetic evidence for the
requirement of inositol polyphosphate signaling in plant sexual reproduction.
PMID- 25846942
TI - Iridium-mediated C-S bond activation and transformation: organoiridium(III)
thioether, thiolato, sulfinato and thiyl radical compounds. Synthesis,
mechanistic, spectral, electrochemical and theoretical aspects.
AB - An attractive methodology, single-electron transfer (SET) reductive cleavage of
the C-S bond mediated by a metal in the presence of the external stimuli PPh3,
has been applied to the kinetically inert IrCl3 in order to synthesize the
thiolato complex [Ir(III)(L(S))Cl(PPh3)2] 3 from precursor thioether complexes
[Ir(III)(L(SR))Cl2(PPh3)] (R = alkyl) 2. The aforesaid cleavage process in
association with (arene)C-H activation furnishes a new class of organosulfur
compounds of iridium(III). The thiolato chelate 3 displays a reversible oxidative
wave at 0.75 V vs. Ag/AgCl signifying its remarkable nucleophilic character. The
high electron density on the thiolato-S vis-a-vis superior nucleophilicity can be
envisaged through the formation of a number of S-centered derivatives. This
observation has been corroborated with the nature of HOMO in 3, which assumes 49%
of S(3p). Notably, the facile oxidative nature of 3 makes it an apposite
precursor for metal-stabilized thiyl radical species. Indeed, iridium(III)
stabilized 3(+) can be generated by chemical/electrochemical means. The axial EPR
spectra with g ~ 2.0 along with theoretical analysis of SOMO (S(3p) 24% + Ph(pi)
43% + d(yz) 15%) and spin density (rho(S) = +0.543, rho(Ph) = +0.315, rho(Ir) =
+0.151) of one-electron oxidized 3(+) validate the iridium-stabilized thiyl
radical description. This observation suggests that the CNS coordination mode in
thiophenolato complex 3 is redox-active. Complex 3 is very prone to S-centered
oxidation under normal aerobic conditions to yield metallosulfoxide
[Ir(III)(L(SO2))Cl(PPh3)2] 4. The enhanced nucleophilicity of thiolato-S can also
be manifested via the smooth S-C bond making process with alkyl halides (R'X, R'
= Me and allyl; X = Br, I) and subsequent formation of thioether complexes of
type [Ir(III)(L(SR'))ClX(PPh3)] 5. The organosulfur compounds of iridium(III)
exhibit rich spectral properties including luminescence and the origin of these
transitions is scrutinized with DFT and TD-DFT methods.
PMID- 25846943
TI - Can feeding-swallowing difficulties in children predict language impairments?
PMID- 25846944
TI - Interleukin-32 stimulates osteosarcoma cell invasion and motility via AKT pathway
mediated MMP-13 expression.
AB - As a pro-inflammatory cytokine, interleukin-32 (IL-32) is reported to play an
important role in tumor development and progression. However, its effects on the
invasion and motility of osteosarcoma cells remain elusive. The aim of the
present study was to determine the molecular mechanisms of IL-32 in osteosarcoma
cells using RT-PCR and western blot analysis. The results showed that IL-32
stimulation dose-dependently promoted the invasion and motility of osteosarcoma
cells. Knockdown of endogenous IL-32 by siRNA inhibited osteosarcoma cell
invasion and motility. Moreover, IL-32 induced the activation of AKT in a time
dependent manner. IL-32 stimulation was also capable of increasing the expression
and secretion of matrix metalloproteinase (MMP)-13, which is involved in tumor
invasion and metastasis. In addition, blockade of AKT activation suppressed IL-32
mediated invasion, motility and MMP-13 upregulation in osteosarcoma cells. Taken
together, our results suggest that IL-32 stimulation promotes the invasion and
motility of osteosarcoma cells, possibly via the activation of AKT and the
upregulation of MMP-13 expression. Thus, IL-32 may serve as a marker for
diagnosis, as well as for the treatment of osteosarcoma.
PMID- 25846945
TI - Plasma concentrations of lidocaine in dogs following lidocaine patch application
over an incision compared to intact skin.
AB - The objective was to compare plasma lidocaine concentrations when a commercially
available 5% lidocaine patch was placed on intact skin vs. an incision. Our
hypothesis was that greater absorption of lidocaine would occur from the incision
site compared to intact skin. Ten dogs were used in a crossover design. A patch
was placed over an incision, and then after a washout period, a patch was placed
over intact skin. Plasma lidocaine concentrations were measured at patch
placement; 20, 40 and 60 min; and 2, 4, 6, 12, 24, 36, 48, 72 and 96 h after
patch placement. After patch removal, the skin was graded using a subjective skin
reaction system. No dogs required rescue analgesia, and no toxicity or skin
reaction was noted. Mean +/- SD AUC and CMAX were 3054.29 +/- 1095.93 ng.h/mL and
54.1 +/- 15.84 ng/mL in the Incision Group, and 2269.9 +/- 1037.08 ng.h/mL and
44.5 +/- 16.34 ng/mL in the No-Incision Group, respectively. The AUC was
significantly higher in the Incision Group. The results of the study demonstrate
that the actual body exposure to lidocaine was significantly higher when an
incision was present compared to intact skin. No adverse effects were observed
from either treatment. Efficacy was not evaluated.
PMID- 25846946
TI - CT AND MRI FEATURES OF CAROTID BODY PARAGANGLIOMAS IN 16 DOGS.
AB - Carotid body tumors (paragangliomas) arise from chemoreceptors located at the
carotid bifurcation. In imaging studies, this neoplasm may be confused with other
neck neoplasms such as thyroid carcinoma. The purpose of this retrospective,
cross-sectional study was to describe computed tomographic (CT) and magnetic
resonance imaging (MRI) characteristics of confirmed carotid body tumors in a
multi-institutional sample of dogs. A total of 16 dogs met inclusion criteria (14
examined using CT and two with MRI). The most common reason for imaging was a
palpable cervical mass or respiratory signs (i.e., dyspnea or increased
respiratory noises). The most commonly affected breed was Boston terrier (n = 5).
Dogs were predominantly male castrated (n = 10) and the median age was 9 years
[range 3-14.5]. Most tumors appeared as a large mass centered at the carotid
bifurcation, with poor margination in six dogs and discrete margins in ten dogs.
Masses were iso- to hypoattenuating to adjacent muscles in CT images and
hyperintense to muscles in T1- and T2-weighted MRI. For both CT and MRI, masses
typically showed strong and heterogeneous contrast enhancement. There was
invasion into the adjacent structures in 9/16 dogs. In six of these nine dogs,
the basilar portion of the skull was affected. The external carotid artery was
entrapped in seven dogs. There was invasion into the internal jugular vein in
three dogs, and into the external jugular, maxillary, and linguo-facial veins in
one dog. Imaging characteristics helped explain some clinical presentations such
as breathing difficulties, Horner's syndrome, head tilt, or facial nerve
paralysis.
PMID- 25846948
TI - Adipose afferent reflex response to insulin is mediated by melanocortin 4 type
receptors in the paraventricular nucleus in insulin resistance rats.
AB - BACKGROUND: Adipose afferent reflex (AAR) contributes to sympathetic activation
and hypertension. Paraventricular nucleus (PVN) plays an important role in AAR
and sympathetic outflow. The aim of the present study was to determine whether
PVN mediates AAR response to insulin in a rat model of insulin resistance (IR).
METHODS: Male Sprague-Dawley rats were randomly divided into Control and IR
groups. Insulin resistance was induced by supplementing fructose (125 g L(-1) ,
12 weeks) in the drinking water. Renal sympathetic nerve activity (RSNA) and mean
arterial pressure (MAP) were recorded in anesthetized rats. AAR was evaluated by
the RSNA and MAP responses to injection of capsaicin into four sites of right
inguinal white adipose tissue. RESULTS: Rats in IR group showed a rise in plasma
noradrenaline (NE), glucose, insulin and triglyceride levels, left ventricular
weight, systolic blood pressure, homeostasis model assessment of insulin
resistance (HOMA-IR) and PVN glucose and insulin levels, melanocortin 4 type
receptors (MC4Rs) protein expression, but not MC3Rs and insulin receptors.
Compared with Control group, AAR in IR group was significantly enhanced, which
contributed to the elevation of NE level; and insulin microinjection into the PVN
or the third ventricle significantly strengthened AAR, which was attenuated by
pre-treatment with MC4Rs antagonist HS024 and anti-insulin affibody,
respectively, but not insulin receptors antagonist S961. CONCLUSION: The enhanced
AAR participates in sympathetic activation in IR, which can be strengthened by
PVN insulin. PVN MC4Rs mediate the AAR response to insulin in IR, but not MC3Rs
and insulin receptors.
PMID- 25846949
TI - Heart rate deflection point during incremental test in competitive agility border
collies.
AB - The aim of this study was to determine a heart rate deflection point (HRdp) in
competitive agility dogs. Fourteen healthy border collies underwent progressive
incremental treadmill exercise--modified Conconi test protocol. Heart rate was
continuously recorded, and the HRdp was estimated using two methods: subjective
and computer aided regression. Maximal heart rate (HRmax), achieved running speed
at the anaerobic threshold and at the end of test were also determined.
Statistical analysis showed a very high positive correlation between HRdp
determined by two methods. The mean HRdp in this research corresponded to 80% of
HRmax. The wide range of individual HRdp (162-229 BPM) indicates the need of an
individual approach in assessing physiological parameters. To the authors'
knowledge, this is the first application of Conconi modified test for estimating
anaerobic threshold in agility dogs since the standard for dogs is yet
undetermined. Future studies need to detect the most appropriate and reliable
technique for its determination as well as its applicability in programming of
the optimal training intensity.
PMID- 25846950
TI - Inflammatory cytokine and acute phase protein concentrations in the peripheral
blood and uterine washings of cows with subclinical endometritis in the late
postpartum period.
AB - The aim of the study was to evaluate the concentrations of proinflammatory
cytokines: tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6), anti
inflammatory cytokine interleukin-10 (IL-10), and acute phase proteins (APPs)-
haptoglobin (Hp) and serum amyloid A (SAA) in serum and uterine washings of cows
with subclinical endometritis, and compare them to healthy animals. The study was
performed on 24 cows on day 60 after delivery. The cows were divided into two
groups based on the results of cytological tests: 12 cows with subclinical
endometritis and 12 healthy cows. Experimental material consisted of blood serum
and uterine washings. The levels of the following cytokines in the study material
were determined with ELISA: TNF-alpha, IL-6, IL-10 and APPs - Hp and SAA. The
results show that the levels of TNF-alpha (p < 0.01), IL-6, IL-10 as well as SAA
and Hp were significantly higher in the serum of cows with subclinical
endometritis compared to the controls (p < 0.001). Uterine washings had
significantly higher levels of IL-6, IL-10, and Hp in the experimental cows
compared to the controls (p < 0.001). The demonstrated differences in the
concentration of cytokines and APP between cows with subclinical endometritis and
healthy cows, in both the serum and uterine washings, may suggest the usefulness
of these parameters in the diagnosis of subclinical endometritis in cows in the
late postpartum period.
PMID- 25846951
TI - Nominal and functional task difficulty in skill acquisition: Effects on
performance in two tests of transfer.
AB - The influence of nominal and functional task difficulty during the acquisition of
a motor skill was examined in two tests of transfer of learning. The task
involved a ballistic, target-directed, finger action. Nominal task difficulty was
defined as the distance of the target from the home position. Functional task
difficulty was created by manipulating the progression of target distances during
practice. Based on the challenge point framework (Guadagnoli & Lee, 2004), we
predicted that practice with a set of targets farther away from the performer
would benefit from less functional task difficulty, while practice with a closer
set of targets would benefit from more functional task difficulty. In single-task
transfer tests, learners who practiced using the high nominal task difficulty
targets benefitted in terms of persistence of performance over time. In dual-task
transfer tests, groups with an intermediate combined (nominal and functional)
task difficulty performed with greater persistence over time on tests of transfer
than those who practiced with the highest or lowest combined difficulty. Together
these findings suggest that the influences of nominal and functional task
difficulty during acquisition are weighted differentially depending upon the
transfer test context. The challenge point framework does not accurately capture
this complex relationship in its current form.
PMID- 25846952
TI - Gender difference in older adult's utilization of gravitational and ground
reaction force in regulation of angular momentum during stair descent.
AB - Angular momentum of the body is a highly controlled quantity signifying
stability, therefore, it is essential to understand its regulation during stair
descent. The purpose of this study was to investigate how older adults use
gravity and ground reaction force to regulate the angular momentum of the body
during stair descent. A total of 28 participants (12 male and 16 female; 68.5
years and 69.0 years of mean age respectively) performed stair descent from a
level walk in a step-over-step manner at a self-selected speed over a custom made
three-step staircase with embedded force plates. Kinematic and force data were
used to calculate angular momentum, gravitational moment, and ground reaction
force moment about the stance foot center of pressure. Women show a significantly
greater change in normalized angular momentum (0.92Nms/Kgm; p=.004) as compared
to men (0.45Nms/Kgm). Women produce higher normalized GRF (p=.031) during the
double support phase. The angular momentum changes show largest backward
regulation for Step 0 and forward regulation for Step 2. This greater difference
in overall change in the angular momentum in women may explain their increased
risk of fall over the stairs.
PMID- 25846953
TI - Surgical resection for hepatocellular carcinoma: Moving from what can be done to
what is worth doing.
PMID- 25846954
TI - Mindfulness training for adolescents: A neurodevelopmental perspective on
investigating modifications in attention and emotion regulation using event
related brain potentials.
AB - Mindfulness training is increasingly being introduced in schools, yet studies
examining its impact on the developing brain have been scarce. A
neurodevelopmental perspective on mindfulness has been advocated as a powerful
tool to enhance our understanding of underlying neurocognitive changes that have
implications for developmental well-being research and the implementation of
mindfulness in education. To stimulate more research in the developmental
cognitive neuroscience of mindfulness, this article outlines possible indexes of
mindfulness-based change in adolescence, with a focus on event-related brain
potential (ERP) markers. We provide methodological recommendations for future
studies and offer examples of research paradigms. We also discuss how mindfulness
practice could impact on the development of prefrontal brain structures and
enhance attention control and emotion regulation skills in adolescents, impacting
in turn on their self-regulation and coping skills. We highlight advantages of
the ERP methodology in neurodevelopmental research of mindfulness. It is proposed
that research using established experimental tasks targeting ERP components such
as the contingent negative variability, N200, error-related negativity and error
positivity, P300, and late positive potential could elucidate developmentally
salient shifts in the neural plasticity of the adolescent brain induced by
mindfulness practice.
PMID- 25846956
TI - Multiple host shifts by the emerging honeybee parasite, Varroa jacobsoni.
AB - Host shifts are a key mechanism of parasite evolution and responsible for the
emergence of many economically important pathogens. Varroa destructor has been a
major factor in global honeybee (Apis mellifera) declines since shifting hosts
from the Asian honeybee (Apis cerana) > 50 years ago. Until recently, only two
haplotypes of V. destructor (Korea and Japan) had successfully host shifted to A.
mellifera. In 2008, the sister species V. jacobsoni was found for the first time
parasitizing A. mellifera in Papua New Guinea (PNG). This recent host shift
presents a serious threat to world apiculture but also provides the opportunity
to examine host shifting in this system. We used 12 microsatellites to compare
genetic variation of V. jacobsoni on A. mellifera in PNG with mites on A. cerana
in both PNG and surrounding regions. We identified two distinct lineages of V.
jacobsoni reproducing on A. mellifera in PNG. Our analysis indicated independent
host shift events have occurred through small numbers of mites shifting from
local A. cerana populations. Additional lineages were found in the neighbouring
Papua and Solomon Islands that had partially host shifted to A. mellifera, that
is producing immature offspring on drone brood only. These mites were likely in
transition to full colonization of A. mellifera. Significant population structure
between mites on the different hosts suggested host shifted V. jacobsoni
populations may not still reproduce on A. cerana, although limited gene flow may
exist. Our studies provide further insight into parasite host shift evolution and
help characterize this new Varroa mite threat to A. mellifera worldwide.
PMID- 25846955
TI - MicroRNA-155 knockout mice are susceptible to Mycobacterium tuberculosis
infection.
AB - MicroRNAs (miRNAs) are short, conserved, non-coding RNA molecules that repress
translation, followed by the decay of miRNA-targeted mRNAs that encode molecules
involved in cell differentiation, development, immunity and apoptosis. At least
six miRNAs, including microRNA-155 (miR-155), were up-regulated when born marrow
derived macrophages from C57BL/6 mice were infected with Mycobacterium
tuberculosis Erdman. C57BL/6 mice intravenously infected with Erdman showed up
regulation of miR-155 in livers and lungs. Following infection, miR-155-deficient
C57BL/6 mice died significantly earlier and had significantly higher numbers of
CFU in lungs than wild-type mice. Moreover, fewer CD4(+) T cells, but higher
numbers of monocytes and neutrophils, were present in the lungs of Erdman
infected miR-155 knockout (miR-155(-/-)) than of wild-type mice. These findings
indicated that miR-155 plays a critical role in immune responses to M.
tuberculosis.
PMID- 25846957
TI - Effects of pre-eclampsia and fetal growth restriction on C-type natriuretic
peptide.
AB - OBJECTIVE: To determine changes in plasma C-type natriuretic peptide (CNP), a
paracrine product of the vascular endothelium, in pregnancies with vascular
disorders, and relate these to time of presentation and severity. DESIGN:
Retrospective nested cases and controls. SETTING: Community study, Auckland New
Zealand. POPULATION: Screening for Pregnancy Endpoints (SCOPE) data and bio-bank
of maternal plasma. METHODS: Maternal plasma amino terminal proCNP (NTproCNP) was
measured by radioimmunoassay in early (14-16 weeks of gestation, and again at 19
21 weeks of gestation) and late (34-36 weeks of gestation) pregnancy in three
groups of women (20 per group): pre-eclampsia (pre-eclampsia); gestational
hypertension (GHT) with small for gestational age (SGA); and uncomplicated
pregnancy. MAIN OUTCOME MEASURES: Change in NTproCNP and associations with
concurrent blood pressure, time of case presentation, severity, and infant
birthweight. RESULTS: Plasma NTproCNP in early pregnancy in women with vascular
disorders did not differ from those found in controls. In late pregnancy, levels
in pre-eclampsia (28.8 +/- 2.3 pM) and in GHT with SGA (28.6 +/- 4.8 pM) were
significantly increased (P = 0.01 and 0.027, respectively) compared with controls
(21.3 +/- 1 pM). In pre-eclampsia, levels were significantly higher (P < 0.03) at
14-16 weeks of gestation in women diagnosed prior to 34 weeks of gestation.
Combining all three groups, associations of NTproCNP with concurrent diastolic
and mean arterial pressure were found at 34-36 weeks of gestation (r = 0.46). No
significant associations were identified with birthweight. CONCLUSIONS: CNP
secretion during gestation is responsive to vascular stress. Plasma NTproCNP
measurements may have clinical application in late pregnancy in defining the
different phenotypes associated with pre-eclampsia.
PMID- 25846958
TI - Soft template strategy to synthesize iron oxide-titania yolk-shell nanoparticles
as high-performance anode materials for lithium-ion battery applications.
AB - Yolk-shell-structured nanoparticles with iron oxide core, void, and a titania
shell configuration are prepared by a simple soft template method and used as the
anode material for lithium ion batteries. The iron oxide-titania yolk-shell
nanoparticles (IO@void@TNPs) exhibit a higher and more stable capacity than
simply mixed nanoparticles of iron oxide and hollow titania because of the unique
structure obtained by the perfect separation between iron oxide nanoparticles, in
combination with the adequate internal void space provided by stable titania
shells. Moreover, the structural effect of IO@void@TNPs clearly demonstrates that
the capacity retention value after 50 cycles is approximately 4 times that for
IONPs under harsh operating conditions, that is, when the temperature is
increased to 80 degrees C.
PMID- 25846959
TI - Adult presentation of X-linked Conradi-Hunermann-Happle syndrome.
AB - Conradi-Hunermann-Happle syndrome, or X-linked dominant chondrodysplasia punctata
type 2 (CDPX2), is a genodermatosis caused by mutations in EBP. While typically
lethal in males, females with CDPX2 generally manifest by infancy or childhood
with variable features including congenital ichthyosiform erythroderma,
chondrodysplasia punctata, asymmetric shortening of the long bones, and
cataracts. We present a 36-year-old female with short stature, rhizomelic and
asymmetric limb shortening, severe scoliosis, a sectorial cataract, and no family
history of CDPX2. Whole exome sequencing (WES) revealed a p.Arg63del mutation in
EBP, and biochemical studies confirmed a diagnosis of CDPX2. Short stature in
combination with ichthyosis or alopecia, cataracts, and limb shortening in an
adult should prompt consideration of a diagnosis of CDPX2. As in many genetic
syndromes, the hallmark features of CDPX2 in pediatric patients are not readily
identifiable in adults. This demonstrates the utility of WES as a diagnostic tool
in the evaluation of adults with genetic disorders.
PMID- 25846960
TI - How Clark's nutcrackers (Nucifraga columbiana) weigh geometric cues depends on
their previous experience.
AB - Following passive disorientation, Clark's nutcrackers (Nucifraga columbiana)
learned to search for a hidden food reward located in one corner of a rectangular
shaped enclosure that contained either identical or distinct features in each
corner. Identical features allowed for explicit learning of geometric cues,
whereas distinct features allowed for both explicit learning of featural cues and
incidental learning of geometric cues. Birds that only learned about geometry
incidentally (group Distinct) weighed features greater than geometry when the two
cues were placed in conflict. However, birds that received explicit training with
geometry, in addition to feature training (groups Distinct-Identical and
Identical-Distinct), weighed geometry heavier relative to features. Cue
preference by the birds also depended on the order in which learning was
experienced; if explicit training with geometry followed that of features (group
Distinct-Identical), then both geometry and features were weighed equally, but if
explicit training with geometry training preceded that of features (group
Identical-Distinct), the birds weighed geometry greater than features. Results
suggest both a heightened sensitivity to geometric cues by Clark's nutcrackers
relative to other species of birds and an increased sensitivity to any spatial
cue (either features or geometry) that has proven both stable and reliable.
PMID- 25846961
TI - Relative versus absolute numerical representation in fish: Can guppies represent
"fourness"?
AB - In recent years, the use of operant conditioning procedures has shown that
species as diverse as chimpanzees, honeybees, and mosquitofish can be trained to
discriminate between sets containing different numbers of objects. However, to
succeed in this task, subjects can use two different strategies: either select
the array containing a specific number of items (an absolute numerosity rule), or
select the set containing the larger (or smaller) quantity of items (a relative
numerosity rule). In the latter case, subjects need not only be able to judge
whether two numerosities are equal or different but also be able to order
numerosities. Here, in two experiments, we address whether fish can perform both
kinds of judgment by training them with specific numerosities and testing their
generalization to new numerosity contrasts. In Experiment 1, subjects were
initially trained to select between visual arrays of 6 and 12 shapes, and were
then tested with a contrast pairing the previously trained numerosity (either 6
or 12) with a novel numerosity (respectively, 3 or 24). Spontaneously, subjects
selected the novel numerosity, in accordance with a relative numerosity rule. The
second experiment tested whether guppies can also learn to select one specific
number against all others, if appropriately trained. Fish trained to select an
array of 4 shapes against several alternatives (4 vs. 1, 4 vs. 2, 4 vs. 8, 4 vs.
10) learned to recognize the number 4 against all alternatives and proved able to
generalize their discrimination to novel, more difficult contrasts (4 vs. 3 and 4
vs. 6 items). In summary, although guppies preferentially opt for relative
comparisons, they can flexibly learn either relative or absolute decision
criteria on numerosity stimuli, depending on the context.
PMID- 25846962
TI - High similarity of U2 snDNA sequence between A and B chromosomes in the
grasshopper Abracris flavolineata.
AB - B chromosomes are frequently enriched for a wide variety of repetitive DNAs.
Among grasshoppers in the species Abracris flavolineata (Ommatolampidinae) the B
chromosomes are submetacentric, C-negative and harbor repetitive DNAs such as, U2
snDNA, C 0 t-1 DNA, two Mariner-like elements and some microsatellites. Here, we
provide evidence showing the intragenome similarity between the B chromosome and
the A complement in A. flavolineata, combining analysis of microdissection and
chromosome painting and B chromosome-specific amplification through polymerase
chain reaction (PCR) of U2 snDNA. Chromosome painting revealed signals spread
through the C-negative regions, including the A and B chromosomes. Moreover,
significant clustered signals forming bands were observed in some A chromosomes,
and for the B chromosome, significant signals were located on both arms, which
could be caused by accumulation of repetitive DNA sequences. The C-positive
regions did not reveal any signals. Sequence comparison of U2 snDNA between that
obtained from a genome without the B chromosome and that from uB-DNA revealed
high similarity with the occurrence of four shared haplotypes, one of them (i.e.,
Hap1) being highly prevalent and putatively ancestral. The highest divergence
from Hap1 was observed for Hap3, which was caused by only six mutational steps.
These data support an intraspecific origin of the B chromosome in A. flavolineata
that is highly similar with the A complement, and the low U2 snDNA sequence
diversity observed in the B chromosome could be related to its recent origin,
besides intrachromosomal concerted evolution for U2 snDNA repeats in the B
chromosome.
PMID- 25846963
TI - Genome-wide identification and characterization of aquaporin gene family in
common bean (Phaseolus vulgaris L.).
AB - Plant aquaporins are a large and diverse family of water channel proteins that
are essential for several physiological processes in living organisms. Numerous
studies have linked plant aquaporins with a plethora of processes, such as
nutrient acquisition, CO2 transport, plant growth and development, and response
to abiotic stresses. However, little is known about this protein family in common
bean. Here, we present a genome-wide identification of the aquaporin gene family
in common bean (Phaseolus vulgaris L.), a legume crop essential for human
nutrition. We identified 41 full-length coding aquaporin sequences in the common
bean genome, divided by phylogenetic analysis into five sub-families (PIPs, TIPs,
NIPs, SIPs and XIPs). Residues determining substrate specificity of aquaporins
(i.e., NPA motifs and ar/R selectivity filter) seem conserved between common bean
and other plant species, allowing inference of substrate specificity for these
proteins. Thanks to the availability of RNA-sequencing datasets, expression
levels in different organs and in leaves of wild and domesticated bean accessions
were evaluated. Three aquaporins (PvTIP1;1, PvPIP2;4 and PvPIP1;2) have the
overall highest mean expressions, with PvTIP1;1 having the highest expression
among all aquaporins. We performed an EST database mining to identify drought
responsive aquaporins in common bean. This analysis showed a significant increase
in expression for PvTIP1;1 in drought stress conditions compared to well-watered
environments. The pivotal role suggested for PvTIP1;1 in regulating water
homeostasis and drought stress response in the common bean should be verified by
further field experimentation under drought stress.
PMID- 25846964
TI - Development of a Hyperactive Primary Hemostatic System During Off-Pump Lung
Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its
Cleaving Protease ADAMTS13.
AB - An unbalance between the platelet-adhesive protein von Willebrand factor (VWF)
and its cleaving protease ADAMTS13 is a risk factor for thrombosis. Here, we
assessed levels and functionality of VWF and ADAMTS13 in patients undergoing off
pump lung transplantation. We analyzed plasma of 10 patients and distinguished
lung transplantation-specific effects from those generally accompanying open
chest surgeries by comparing results with 11 patients undergoing off-pump
coronary bypass graft (CABG) surgery. Forty healthy volunteers were included for
reference values. VWF antigen levels as well as the VWF ristocetin cofactor
activity/VWF antigen ratio increased during lung transplantation and after CABG
surgery. An increase in VWF propeptide levels was paralleled by a decrease in
ADAMTS13 activity. This was more pronounced during lung transplantation.
Similarly, the capacity of plasma to support platelet aggregation under shear
flow conditions in vitro was more increased during lung transplantation. The
proportion of high molecular weight VWF multimers was elevated in both groups
without evidence for ultra-large VWF. VWF's collagen binding activity remained
unchanged. In conclusion, a hyperactive primary hemostatic system develops during
lung transplantation resulting both from a pronounced (functional) increase of
the VWF molecule and decrease of ADAMTS13. This may increase the risk of platelet
thrombosis within the allograft.
PMID- 25846965
TI - Enzymes for synthetic biology of ambroxide-related diterpenoid fragrance
compounds.
AB - Ambrox and related ambroxides are highly priced in the fragrance industry, and
valued for their delicate odor and fixative properties. Historically, ambrox was
obtained from ambergris, a waxy excretion produced by sperm whales, now an
endangered species. Synthetic ambroxides have replaced ambergris in perfume
manufacture. Plant labdane diterpenoids can serve as starting material for
ambroxide synthesis. Among these, the diterpene alcohol sclareol is the major
industrial precursor obtained from cultivated clary sage (Salvia sclarea). In
plants, a large family of diterpene synthase (diTPS) enzymes controls key
reactions in diterpenoid biosynthesis. Advanced metabolite profiling and high
throughput sequencing of fragrant and medicinal plants have accelerated discovery
of novel diTPS functions, providing a resource for combinatorial synthetic
biology and metabolic engineering approaches. This chapter highlights recent
progress on the discovery, characterization, and engineering of plant diTPSs with
potential uses in ambroxide production. It features biosynthesis of sclareol, cis
abienol, and diterpene resin acids, as sources of genes and enzymes for
diterpenoid bioproducts.
PMID- 25846977
TI - Canine orbital rhabdomyosarcoma: a report of 18 cases.
AB - PURPOSE: To describe clinical and pathological features of canine orbital
rhabdomyosarcoma (COR). METHODS: Retrospective review of patients with COR from
the archives of the Comparative Ocular Pathology Laboratory of Wisconsin and the
University of Wisconsin Veterinary Medical Teaching Hospital (1983-2014).
RESULTS: Eighteen cases of COR were identified, all diagnosed in an 8-year period
(2006-2014). Affected dogs were typically young (range 1-8; median 2 years), and
both sexes were equally represented. Common clinical signs included exophthalmos
(16/18) with dorsolateral deviation of the globe (10/18) and elevation of the
nictitans (12/18). Ultrasonography, performed in nine cases, revealed an orbital
mass with mixed echogenicity and posterior globe indentation. Advanced imaging,
performed in nine cases, demonstrated a soft tissue mass with variable contrast
enhancement and lysis of the orbital bones (5/9). Histologically, all tumors were
subclassified as embryonal rhabdomyosarcoma. All neoplasms demonstrated positive
immunohistochemical labeling for desmin, and 14/18 were positive for skeletal
muscle actin. Follow-up information was available for 15/18 cases. Older dogs,
aged 6-8 years, had no clinical signs of recurrence or metastasis 8-13 months
postdiagnosis (4/4). Most younger dogs (9/11), aged 1-4 years, were euthanized
within 6 months (median 2.5 months) of diagnosis due to recurrence at the
surgical site (5/9) and/or metastasis (5/9). CONCLUSIONS: Canine orbital
rhabdomyosarcoma is a highly malignant neoplasm in juvenile dogs, but may be
amenable to surgical resection in older dogs. This duality in biologic behavior
may reflect differences in tissue of origin between juvenile onset tumors and
adult onset tumors.
PMID- 25846978
TI - Thermal oxidation of cholesterol: Preliminary evaluation of 2-methyl-6-heptanone
and 3-methylbutanal as volatile oxidation markers.
AB - Cholesterol oxidation in food and model systems is usually monitored by
evaluating cholesterol oxidation products, but the analysis is time-consuming and
expensive. Therefore, the determination of volatile compounds deriving from
cholesterol thermoxidation could be valuable to identify other possible oxidation
markers. Cholesterol alone and in the presence of a triacylglycerol mixture
(tripalmitin, tristearin, and triolein) were thermoxidized at 170 degrees C for
15min. In both model systems, the total volatile compounds increased three times
when oxidation time rose from 5 to 15min. The main classes of volatile compounds
were aldehydes, ketones, alcohols and hydrocarbons, displaying a similar behavior
in both systems. After 5min of oxidation, 2-methyl-6-heptanone was the main
volatile compound, followed by 3-methylpentane, 2,3-dimethyl-1-pentene and 3
methylbutanal. To verify if 2-methyl-6-heptanone could be used as volatile marker
of cholesterol oxidation, data were compared with the total cholesterol oxidation
products content of each system. A significant correlation between total
cholesterol oxidation products content and 2-methyl-6-heptanone amount was found
when cholesterol was oxidized alone (r(2)=0.994) and in presence of
triacylglycerols (r(2)=0.998). When egg yolk was thermoxidized at 80 degrees C
for 6h, 3-methylbutanal was the volatile compound that better explained the
oxidative trend in this food system, showing a significant correlation with
cholesterol oxidation rate (r=0.91). In conclusion, 2-methyl-6-heptanone and 3
methylbutanal could represent an easy and cheaper strategy for monitoring
cholesterol oxidation in model systems and food samples, respectively; however, a
deeper investigation on the amount and type of volatile compounds generated from
cholesterol oxidation according to the food matrix, should be carried out.
PMID- 25846979
TI - Steroid biosynthesis in adipose tissue.
AB - Tissue-specific expression of steroidogenic enzymes allows the modulation of
active steroid levels in a local manner. Thus, the measurement of local steroid
concentrations, rather than the circulating levels, has been recognized as a more
accurate indicator of the steroid action within a specific tissue. Adipose
tissue, one of the largest endocrine tissues in the human body, has been
established as an important site for steroid storage and metabolism. Locally
produced steroids, through the enzymatic conversion from steroid precursors
delivered to adipose tissue, have been proven to either functionally regulate
adipose tissue metabolism, or quantitatively contribute to the whole body's
steroid levels. Most recently, it has been suggested that adipose tissue may
contain the steroidogenic machinery necessary for the initiation of steroid
biosynthesis de novo from cholesterol. This review summarizes the evidence
indicating the presence of the entire steroidogenic apparatus in adipose tissue
and discusses the potential roles of local steroid products in modulating adipose
tissue activity and other metabolic parameters.
PMID- 25846980
TI - Positing, fitting, and selecting regression models for pooled biomarker data.
AB - Pooling biospecimens prior to performing lab assays can help reduce lab costs,
preserve specimens, and reduce information loss when subject to a limit of
detection. Because many biomarkers measured in epidemiological studies are
positive and right-skewed, proper analysis of pooled specimens requires special
methods. In this paper, we develop and compare parametric regression models for
skewed outcome data subject to pooling, including a novel parameterization of the
gamma distribution that takes full advantage of the gamma summation property. We
also develop a Monte Carlo approximation of Akaike's Information Criterion
applied to pooled data in order to guide model selection. Simulation studies and
analysis of motivating data from the Collaborative Perinatal Project suggest that
using Akaike's Information Criterion to select the best parametric model can help
ensure valid inference and promote estimate precision.
PMID- 25846981
TI - Identification of a chronic non-neurodegenerative microglia activation state in a
mouse model of peroxisomal beta-oxidation deficiency.
AB - The functional diversity and molecular adaptations of reactive microglia in the
chronically inflamed central nervous system (CNS) are poorly understood. We
previously showed that mice lacking multifunctional protein 2 (MFP2), a pivotal
enzyme in peroxisomal beta-oxidation, persistently accumulate reactive myeloid
cells in the gray matter of the CNS. Here, we show that the increased numbers of
myeloid cells solely derive from the proliferation of resident microglia and not
from infiltrating monocytes. We defined the signature of Mfp2(-/-) microglia by
gene expression profiling after acute isolation, which was validated by
quantitative polymerase reaction (qPCR), immunohistochemical, and flow cytometric
analysis. The features of Mfp2(-/-) microglia were compared with those from
SOD1(G93A) mice, an amyotrophic lateral sclerosis model. In contrast to the
neurodegenerative milieu of SOD1(G93A) spinal cord, neurons were intact in Mfp2(
/-) brain and Mfp2(-/-) microglia lacked signs of phagocytic and neurotoxic
activity. The chronically reactive state of Mfp2(-/-) microglia was accompanied
by the downregulation of markers that specify the unique microglial signature in
homeostatic conditions. In contrast, mammalian target of rapamycin (mTOR) and
downstream glycolytic and protein translation pathways were induced, indicative
of metabolic adaptations. Mfp2(-/-) microglia were immunologically activated but
not polarized to a pro- or anti-inflammatory phenotype. A peripheral
lipopolysaccharide challenge provoked an exaggerated inflammatory response in
Mfp2(-/-) brain, consistent with a primed state. Taken together, we demonstrate
that chronic activation of resident microglia does not necessarily lead to
phagocytosis nor overt neurotoxicity.
PMID- 25846982
TI - Race/Ethnicity and Treatment Outcome in a Randomized Controlled Trial for
Trichotillomania (Hair-Pulling Disorder).
AB - OBJECTIVE: Treatment outcome was compared among non-Hispanic White and
racial/ethnic minority participants with trichotillomania (TTM), or hair-pulling
disorder. METHOD: Symptom severity, quality of life, and TTM-related disability
were compared in a behavior therapy trial with a stepped care approach: web-based
self-help and then individual behavior therapy. The sample comprised 72% (n = 38)
non-Hispanic White participants and 28% (n = 15) minority participants. RESULTS:
The ethnic groups responded differently to treatment, with fewer minority
participants showing improvement during web-based self-help. Response rates were
equivalent between ethnic groups during the in-person behavior therapy. These
results should be interpreted with caution because of the small sample size of
minorities in the study and consequent inability to analyze results for each
racial/ethnic group individually. CONCLUSIONS: Future studies should focus on the
investigation of factors that may enable or hinder racial and ethnic minority
participants to benefit from online and/or self-help behavior therapy for TTM.
PMID- 25846983
TI - Polyhydroxyalkanoate (PHA) storage within a mixed-culture biomass with
simultaneous growth as a function of accumulation substrate nitrogen and
phosphorus levels.
AB - The response of a mixed-microbial-culture (MMC) biomass for PHA accumulation was
evaluated over a range of relative nitrogen (N) and phosphorus (P) availabilities
with respect to the supply of either complex (fermented whey permeate - FWP) or
simpler (acetic acid) organic feedstocks. Fed-batch feed-on-demand PHA
accumulation experiments were conducted where the feed N/COD and P/COD ratios
were varied ranging from conditions of nutrient starvation to excess. A feast
famine enrichment (activated sludge) biomass, produced in a pilot-scale aerobic
sequencing batch reactor on FWP and with a long history of stable PHA
accumulation performance, was used for all the experiments as reference material.
FWP with N/COD ratios of (2, 5, 15, 70 mg/g all with P/COD = 8 mg/g) as well as
simulated FWP with nutrient starvation (N/COD = P/COD = 0) conditions were
applied. For the acetic acid accumulations, nutrient starvation as well as N/COD
variations (2.5, 5, 50 mg/g all with P/COD = 9 mg/g) and P/COD variations (0.5,
2, 9, 15 mg/g all with N/COD = 10 mg/g) were evaluated. An optimal range of
combined N and P limitation with N/COD from 2 to 15 mg/g and P/COD from 0.5 to 3
mg/g was considered to offer consistent improvement of productivity over the case
of nutrient starvation. Productivity increased due to active biomass growth of
the PHA storing biomass without observed risk for a growth response overtaking
PHA storage activity. PHA production with respect to the initial active biomass
was significantly higher even in cases of excess nutrient additions when compared
to the cases of nutrient starvation. The 24-h PHA productivities were enhanced as
much as 4-fold from a base value of 1.35 g-PHA per gram initial active biomass
with respect nutrient starvation feedstock. With or without nutrient loading the
biomass consistently accumulated similar and significant PHA (nominally 60% g
PHA/g-VSS). Based on results from replicate experiments some variability in the
extant biomass maximum PHA content was attributed to interpreted differences in
the biomass initial physiological state and not due to changes in feedstock
nutrient loading. We found that the accumulation process production rates for
mixed cultures can be sustained long after the maximum PHA content of the biomass
was reached. Within the specific context of the applied fed-batch feed-on-demand
methods, active biomass growth was interpreted to have been largely restricted to
the PHA-storing phenotypic fraction of the biomass. This study suggests practical
prospects for mixed culture PHA production using a wide range of volatile fatty
acid (VFA) rich feedstocks. Such VFA sources derived from residual industrial or
municipal organic wastes often naturally contain associated nutrients ranging in
levels from limitation to excess.
PMID- 25846984
TI - Microbial fuel cell biosensor for rapid assessment of assimilable organic carbon
under marine conditions.
AB - The development of an assimilable organic carbon (AOC) detecting marine microbial
fuel cell (MFC) biosensor inoculated with microorganisms from marine sediment was
successful within 36 days. This established marine MFC was tested as an AOC
biosensor and reproducible microbiologically produced electrical signals in
response to defined acetate concentration were achieved. The dependency of the
biosensor sensitivity on the potential of the electron-accepting electrode
(anode) was investigated. A linear correlation (R(2) > 0.98) between
electrochemical signals (change in anodic potential and peak current) and acetate
concentration ranging from 0 to 150 MUM (0-3600 MUg/L of AOC) was achieved.
However, the present biosensor indicated a different-linear relation at somewhat
elevated acetate concentration ranging from 150 to 450 MUM (3600-10,800 MUg/L of
AOC). This high concentration of acetate addition could be measured by coulombic
measurement (cumulative charges) with a linear correlation. For the acetate
concentration detected in this study, the sensor recovery time could be
controlled within 100 min.
PMID- 25846985
TI - Regeneration of iron-based adsorptive media used for removing arsenic from
groundwater.
AB - Adsorptive media technology is regarded as a simple, low cost method of removing
arsenic from drinking water particularly for small systems. Currently, when the
effluent of a treatment system reaches the USEPA maximum contaminant level (MCL)
of 10 ug/L, the exhausted media is removed and replaced by new virgin media.
Although the commonly used iron-based media products are reasonable in price, the
replacement cost accounts for around 80% of the systems total operational costs.
One option to media replacement is on-site regeneration and reuse of the
exhausted media. To determine whether an iron based media can be successfully
regenerated and reused, laboratory batch and column regeneration tests were
conducted on six exhausted iron-based media products obtained from six full scale
arsenic removal treatment systems. Batch tests conducted on three of the media
products to evaluate the effectiveness of 1-6% caustic regenerant solutions found
that arsenic desorption increased until around 4%. Using 4% caustic solutions,
the columns tests on the six exhausted media products showed arsenic removals
ranged from 25 to 90% with the best results obtained with the Severn Trent E33
media. Exposing the media to caustic (pH >= 13) and acid (pH <= 2) solutions
found minimal media loss with the caustic solution, but significant media
dissolution with a pH 2 acid solution. A six column pilot plant test at an Ohio
test site with the lab regenerated media products found that the regenerated
media could achieve arsenic removals somewhat similar to virgin media.
PMID- 25846986
TI - Animal models of Epstein Barr virus infection.
AB - Epstein Barr virus (EBV) was the first human tumor virus to be described. Despite
its discovery now more than fifty years ago, immune control of this virus is
still not very well understood and no vaccine is available. This knowledge gap is
due in part to the lack of a preclinical small animal model which can faithfully
recapitulate EBV infection and immune control, and would allow testing of EBV
specific vaccine candidates. With the advent of mice with reconstituted human
immune system compartments (HIS mice) during the past decade this is changing. We
will discuss which aspects of EBV infection and its immune control can already be
modeled in HIS mice, and which shortcomings still need to be overcome in order to
recapitulate the immunobiology of oncogenic EBV infection.
PMID- 25846987
TI - Oncolytic bovine herpesvirus type 1 as a broad spectrum cancer therapeutic.
AB - Oncolytic viruses selectively replicate in tumor cells and elicit antitumor
effects in vivo by both direct and indirect methods. They are attractive avenues
of cancer therapy due to the absence of toxic side effects often seen in current
treatment modalities. Bovine herpesvirus type 1 (BHV-1) holds promise as a broad
spectrum oncolytic vector that is able to infect and kill human tumor cells from
a variety of histological origins, including cancer-initiating cells. In the
majority of cases, BHV-1 elicits tumor cell death in the absence of a productive
infection. In vivo, BHV-1 affects the incidence of secondary lesions in cotton
rats bearing subcutaneous breast adenocarcinomas. These recent studies contribute
to the characterization of BHV-1 as an oncolytic virus.
PMID- 25846988
TI - Potentiating oncolytic viral therapy through an understanding of the initial
immune responses to oncolytic viral infection.
AB - Despite the challenge of implementing oncolytic viral therapy into mainstream
clinical use, the obstacles of early clinical trials have outlined numerous areas
requiring additional investigation. In particular, the role of innate and
adaptive immunity has received significant attention in this context. It is
increasingly clear that a one-sided approach of either immune suppression or
robust immune cell activation is not the answer for clinical success. Rather,
recent studies are increasingly demonstrating the delicate balance between both
anti-viral immune suppression and immune mediated tumor killing. In this review
we focus on aspects of innate immune cell activation following oncolytic viral
infection and how this response has the potential of bridging to the broader goal
of viral mediated immunotherapy.
PMID- 25846993
TI - Conflict management style, supportive work environments and the experience of
work stress in emergency nurses.
AB - AIMS: To examine the conflict management style that emergency department (ED)
nurses use to resolve conflict and to determine whether their style of managing
conflict and a supportive work environment affects their experience of work
stress. BACKGROUND: Conflict is a common stressor that is encountered as nurses
strive to achieve patient satisfaction goals while delivering quality care. How a
nurse perceives support may impact work stress levels and how they deal with
conflict. METHODS: A correlational design examined the relationship between
supportive work environment, and conflict management style and work stress in a
sample of 222 ED nurses using the expanded nurse work stress scale; the survey of
perceived organisational support; and the Rahim organisational conflict inventory
II. RESULTS: Twenty seven percent of nurses reported elevated levels of work
stress. A supportive work environment and avoidant conflict management style were
significant predictors of work stress. CONCLUSIONS: Findings suggest that ED
nurses' perception of a supportive work environment and their approach to
resolving conflict may be related to their experience of work stress.
IMPLICATIONS FOR NURSING MANAGEMENT: Providing opportunities for ED nurses in
skills training in constructive conflict resolution may help to reduce work
stress and to improve the quality of patient care.
PMID- 25846994
TI - Regional movement patterns of a small-bodied shark revealed by stable-isotope
analysis.
AB - This study used stable-isotope analysis to define the nearshore regional
residency and movements of the small-bodied Australian sharpnose shark
Rhizoprionodon taylori. Plasma and muscle delta(13) C and delta(15) N of R.
taylori were collected from across five embayments and compared with values of
seagrass and plankton from each bay. Linear distances between adjacent bays
ranged from 30 to 150 km. There was a positive geographic correlation between R.
taylori tissue and environmental delta(13) C values. Populations with the highest
tissue delta(15) N were collected from bays that had the highest environmental
delta(15) N values. These results suggest that R. taylori did not forage more
than 100 km away from their capture location within 6 months to 1 year. The
successful application of isotope analysis to define R. taylori movement
demonstrates that this technique may be used in addition to traditional methods
to study the movement of sharks, even within similar habitats across regionally
small spatial scales (<100 km).
PMID- 25846995
TI - Quality improvement in neurology: Epilepsy Update Quality Measurement Set.
PMID- 25846996
TI - MRI detection of prion protein plaques in variant Creutzfeldt-Jakob disease.
PMID- 25846997
TI - Owl's eye sign: A rare neuroimaging finding in flail arm syndrome.
PMID- 25846998
TI - Quantitative susceptibility mapping suggests a paramagnetic effect in PML.
PMID- 25846999
TI - Opioids for chronic noncancer pain: A position paper of the American Academy of
Neurology.
PMID- 25847000
TI - Clinical Reasoning: A 57-year-old woman who developed acute amnesia following
fever and upper respiratory symptoms.
PMID- 25847001
TI - Teaching NeuroImages: Primary dural mucosa-associated lymphoid tissue lymphoma.
PMID- 25847002
TI - Teaching NeuroImages: Acute neurologic deficits due to Balo concentric sclerosis.
PMID- 25847003
TI - 3D Modeling of dengue virus NS4B and Chikungunya virus nsP4: identification of a
common drug target and designing a single antiviral inhibitor.
AB - Dengue and chikungunya virus infections are one of the major causes of morbidity
and mortality in tropical and sub-tropical regions of the world. These two
viruses belong to two different families with many similarities and
dissimilarities. Both are enveloped viruses and the mode of transmission is also
by the same mosquito species. Especially in case of symptom expression, there is
confusion between these two viruses. Reports indicate the overlapping endemic
areas and co-infections of both viruses in a single patient. The above factors
indicate that there is a need for developing a single drug/vaccine for both the
viruses. As a first report in this direction, we have used the bioinformatics
tools to identify a common target in both the viruses for a single inhibitor
molecule. Phylogenetic and distance based analyses using the nucleotide sequences
of arthropod and non-arthropod borne viruses indicated a common origin of
evolutionary point for mosquito borne viruses, irrespective of their families.
Similarly, the amino acid sequences of non-structural protein-4B (NS4B) of dengue
virus and non-structural protein-P4 (nsP4) of chikungunya virus showed a common
evolutionary origin. Modeled and superimposed 3D-structures of above two proteins
showed a common alpha helix. Virtual screening of selected molecules was done to
identify the molecules which can bind to the identified common helix and found
that N-(p-tolylmethyl)-3-[(3-pyridylmethylamino)methyl]benzamide (TPB) has
significant binding characteristics to the common helix. Molecular simulations
indicated that both the protein-TPB complexes were stable. Therefore, we propose
that TPB or its analogues could act as antiviral agents against both the viruses.
PMID- 25847004
TI - The bZIP transcription factor PfZipA regulates secondary metabolism and oxidative
stress response in the plant endophytic fungus Pestalotiopsis fici.
AB - The bZIP transcription factors are conserved in all eukaryotes and play critical
roles in organismal responses to environmental challenges. In filamentous fungi,
several lines of evidence indicate that secondary metabolism (SM) is associated
with oxidative stress mediated by bZIP proteins. Here we uncover a connection
with a bZIP protein and oxidative stress induction of SM in the plant endophytic
fungus Pestalotiopsis fici. A homology search of the P. fici genome with the bZIP
protein RsmA, involved in SM and the oxidative stress response in Aspergillus
nidulans, identified PfZipA. Deletion of PfzipA resulted in a strain that
displayed resistant to the oxidative reagents tert-butylhydroperoxide (tBOOH),
diamide, and menadione sodium bisulfite (MSB), but increased sensitivity to H2O2
as compared to wild type (WT). Secondary metabolite production presented a
complex pattern dependent on PfzipA and oxidative reagents. Without oxidative
treatment, the DeltaPfzipA strain produced less isosulochrin and ficipyroneA than
WT; addition of tBOOH further decreased production of iso-A82775C and
pestaloficiol M in DeltaPfzipA; diamide treatment resulted in equivalent
production of isosulochrin and ficipyroneA in the two strains; MSB treatment
further decreased production of RES1214-1 and iso-A82775C but increased
pestaloficiol M production in the mutant; and H2O2 treatment resulted in enhanced
production of isosulochrin, RES1214-1 and pestheic acid but decreased ficipyroneA
and pestaloficiol M in DeltaPfzipA compared to WT. Our results suggest that
PfZipA regulation of SM is modified by oxidative stress pathways and provide
insights into a possible role of PfZipA in mediating SM synthesis in the
endophytic lifestyle of P. fici.
PMID- 25847005
TI - MetaMapR: pathway independent metabolomic network analysis incorporating
unknowns.
AB - Metabolic network mapping is a widely used approach for integration of
metabolomic experimental results with biological domain knowledge. However,
current approaches can be limited by biochemical domain or pathway knowledge
which results in sparse disconnected graphs for real world metabolomic
experiments. MetaMapR integrates enzymatic transformations with metabolite
structural similarity, mass spectral similarity and empirical associations to
generate richly connected metabolic networks. This open source, web-based or
desktop software, written in the R programming language, leverages KEGG and
PubChem databases to derive associations between metabolites even in cases where
biochemical domain or molecular annotations are unknown. Network calculation is
enhanced through an interface to the Chemical Translation System, which allows
metabolite identifier translation between >200 common biochemical databases.
Analysis results are presented as interactive visualizations or can be exported
as high-quality graphics and numerical tables which can be imported into common
network analysis and visualization tools. AVAILABILITY AND IMPLEMENTATION: Freely
available at http://dgrapov.github.io/MetaMapR/. Requires R and a modern web
browser. Installation instructions, tutorials and application examples are
available at http://dgrapov.github.io/MetaMapR/. CONTACT: ofiehn@ucdavis.edu.
PMID- 25847006
TI - Stratifying tumour subtypes based on copy number alteration profiles using next
generation sequence data.
AB - MOTIVATION: The role of personalized medicine and target treatment in the
clinical management of cancer patients has become increasingly important in
recent years. This has made the task of precise histological substratification of
cancers crucial. Increasingly, genomic data are being seen as a valuable
classifier. Specifically, copy number alteration (CNA) profiles generated by next
generation sequencing (NGS) can become a determinant for tumours subtyping. The
principle purpose of this study is to devise a model with good prediction
capability for the tumours histological subtypes as a function of both the
patients covariates and their genome-wide CNA profiles from NGS data. RESULTS: We
investigate a logistic regression for modelling tumour histological subtypes as a
function of the patients' covariates and their CNA profiles, in a mixed model
framework. The covariates, such as age and gender, are considered as fixed
predictors and the genome-wide CNA profiles are considered as random predictors.
We illustrate the application of this model in lung and oral cancer datasets, and
the results indicate that the tumour histological subtypes can be modelled with a
good fit. Our cross-validation indicates that the logistic regression exhibits
the best prediction relative to other classification methods we considered in
this study. The model also exhibits the best agreement in the prediction between
smooth-segmented and circular binary-segmented CNA profiles. AVAILABILITY AND
IMPLEMENTATION: An R package to run a logistic regression is available in
http://www1.maths.leeds.ac.uk/~arief/R/CNALR/. CONTACT: a.gusnanto@leeds.ac.uk
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
online.
PMID- 25847007
TI - EBSeq-HMM: a Bayesian approach for identifying gene-expression changes in ordered
RNA-seq experiments.
AB - MOTIVATION: With improvements in next-generation sequencing technologies and
reductions in price, ordered RNA-seq experiments are becoming common. Of primary
interest in these experiments is identifying genes that are changing over time or
space, for example, and then characterizing the specific expression changes. A
number of robust statistical methods are available to identify genes showing
differential expression among multiple conditions, but most assume conditions are
exchangeable and thereby sacrifice power and precision when applied to ordered
data. RESULTS: We propose an empirical Bayes mixture modeling approach called
EBSeq-HMM. In EBSeq-HMM, an auto-regressive hidden Markov model is implemented to
accommodate dependence in gene expression across ordered conditions. As
demonstrated in simulation and case studies, the output proves useful in
identifying differentially expressed genes and in specifying gene-specific
expression paths. EBSeq-HMM may also be used for inference regarding isoform
expression. AVAILABILITY AND IMPLEMENTATION: An R package containing examples and
sample datasets is available at Bioconductor. CONTACT: kendzior@biostat.wisc.edu
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
online.
PMID- 25847008
TI - Gene selection for the reconstruction of stem cell differentiation trees: a
linear programming approach.
AB - MOTIVATION: Stem cell differentiation is largely guided by master transcriptional
regulators, but it also depends on the expression of other types of genes, such
as cell cycle genes, signaling genes, metabolic genes, trafficking genes, etc.
Traditional approaches to understanding gene expression patterns across multiple
conditions, such as principal components analysis or K-means clustering, can
group cell types based on gene expression, but they do so without knowledge of
the differentiation hierarchy. Hierarchical clustering can organize cell types
into a tree, but in general this tree is different from the differentiation
hierarchy itself. METHODS: Given the differentiation hierarchy and gene
expression data at each node, we construct a weighted Euclidean distance metric
such that the minimum spanning tree with respect to that metric is precisely the
given differentiation hierarchy. We provide a set of linear constraints that are
provably sufficient for the desired construction and a linear programming
approach to identify sparse sets of weights, effectively identifying genes that
are most relevant for discriminating different parts of the tree. RESULTS: We
apply our method to microarray gene expression data describing 38 cell types in
the hematopoiesis hierarchy, constructing a weighted Euclidean metric that uses
just 175 genes. However, we find that there are many alternative sets of weights
that satisfy the linear constraints. Thus, in the style of random-forest
training, we also construct metrics based on random subsets of the genes and
compare them to the metric of 175 genes. We then report on the selected genes and
their biological functions. Our approach offers a new way to identify genes that
may have important roles in stem cell differentiation. CONTACT: tperkins@ohri.ca
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
online.
PMID- 25847009
TI - Tumoural Expression of Connective Tissue Growth Factor (CTGF) Impacts on Survival
in Patients Diagnosed with Hepatocellular Carcinoma (HCC).
AB - BACKGROUND: Hepatocellular carcinoma (HCC) tends to develop in the liver when
there is a high level of background inflammation (cirrhosis). Treatment options
are limited and mainly based on systemic therapies such as anti-angiogenic drugs
(e.g. sorafenib). Connective tissue growth factor (CTGF) is a matricellular
protein involved in inflammation, tumour growth and angiogenesis. The aim of this
study is to determine the expression of CTGF and hypoxia inducible factors (HIF)
in HCC and to clarify its impact on relapse and survival. MATERIAL AND METHODS:
Eligibility criteria for the study consisted of patients with a diagnosis of HCC,
formalin-fixed and paraffin-embedded (FFPE) biopsy tissue, as well as relapse and
available survival data. A tissue microarray was constructed from >= 70% tumoural
sections. The expressions of CTGF, HIF1alpha and HIF2alpha were analysed by
immunohistochemistry. The relationship between expression of CTGF/HIF1alpha and
CTGF/HIF2alpha were analysed. Univariate and multivariate analyses were
performed. RESULTS: Fifty-three patients were screened; 39 patients were eligible
for this study. Patients were treated with radical intent. At the end of follow
up, 59% patients relapsed (28.2% locally, 10.3% multicentric liver relapse and
7.7% distant metastases). Estimated median disease-free survival (DFS) and
overall survival (OS) were 23.4 (95%CI 7.18-39.66) and 38.6 months (95%CI 30.7
46.6), respectively. Expression of CTGF was: negative 23.1%, focal 48.7% and
diffuse 23.1%. A non-statistically significant relationship between expression of
CTGF and HIF was shown supporting an alternative pathway for CTGF expression in
HCC. In multivariate analysis CTGF expression was an independent factor related
to OS, with shorter survival in those patients with focal/diffuse CTGF expression
(HR 2.46; 95%CI 1.18-5.15). CONCLUSIONS: Our results support that expression of
CTGF is an independent factor associated with shorter OS in HCC. Further analysis
of CTGF expression in a larger series of HCC patients is required to confirm CTGF
as a prognostic biomarker in HCC.
PMID- 25847010
TI - Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.
AB - Drug delivery systems are under intense investigation all around the world,
especially in oncology research. Indeed, in some cases, like bone metastasis,
nanodrugs may represent the last and best choice for both treatment and imaging
of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as
radiopharmaceuticals for many years; however, their use as
nanoradiopharmaceuticals is very innovative and creates a new way to establish
radiopharmacy in this new scenario offered by nanotechnology. In this study we
developed and tested nano-MDP-labelled with 99mTc in rats induced with bone
cancer metastasis and the results showed that it may work in patients. However,
some further experiments are required in order to initiate protocols in humans.
PMID- 25847011
TI - Near-infrared Light Activatable Multimodal Gold Nanostructures Platform: An
Emerging Paradigm for Cancer Therapy.
AB - Traditional therapy for cancer is subject to some evident obstacles, including
low effectiveness, resistance, systemic complication, etc. Gold nanostructures
responsive to near-infrared (NIR) light are attractive for non-invasive and
targeted therapy because of their unique physical properties especially strong
absorption and scattering, and high surface area-to-volume ratio as well as the
ease of which their surface chemistry can be manipulated to enhance
biocompatibility surface modification and functionalization. In this Review, the
progress of photothermal therapy (PTT) as well as the targeted delivery of
anticancer agents as the predominant applications of gold nanostructures is
detailed, with a focus on imaging-guided therapy and optimizing operational
parameters. The NIR light-controlled targeted delivery and/or photothermal
ablation of gold nanostructures in the treatment of metastasis are also briefly
discussed. These gold nanostructures pave the way for developing better
therapeutic strategies of cancer.
PMID- 25847012
TI - Acute ataxic neuropathy associated with hepatitis E virus infection.
PMID- 25847013
TI - Reducing radiation in chronic total occlusion percutaneous coronary
interventions.
AB - The field of percutaneous intervention for chronic total occlusion (CTO) has
enjoyed significant innovations in the recent years. Novel techniques and
technologies have revolutionized the field and have resulted in considerably
higher success rates even in patients with high anatomical complexity. Successful
CTO recanalization is associated with significant clinical benefits, such as the
improvement of angina and quality of life, reduced rates of surgical
revascularization, improvement of left ventricular function and decreased
mortality rates. However, complex CTO procedures often require prolonged x-ray
exposure which have been associated with adverse long term outcomes.
PMID- 25847014
TI - Antagonism between MCL-1 and PUMA governs stem/progenitor cell survival during
hematopoietic recovery from stress.
AB - Understanding the critical factors that govern recovery of the hematopoietic
system from stress, such as during anticancer therapy and bone marrow
transplantation, is of clinical significance. We investigated the importance of
the prosurvival proteins myeloid cell leukemia-1 (MCL-1) and B-cell lymphoma
extra large (BCL-XL) in stem/progenitor cell survival and fitness during
hematopoietic recovery from stress. Loss of a single Mcl-1 allele, which reduced
MCL-1 protein levels, severely compromised hematopoietic recovery from
myeloablative challenge and following bone marrow transplantation, whereas BCL-XL
was dispensable in both contexts. We identified inhibition of proapoptotic p53
upregulated modulator of apoptosis (PUMA) as the key role of MCL-1 in both
settings, with Mcl-1(+/-);Puma(-/-) mice completely protected from the
deleterious effects of loss of 1 Mcl-1 allele. These results reveal the molecular
mechanisms that govern cell survival during hematopoietic recovery from stress.
PMID- 25847015
TI - T memory stem cells are the hierarchical apex of adult T-cell leukemia.
AB - Adult T-cell leukemia (ATL) is a peripheral CD4(+) T-cell neoplasm caused by
human T-cell leukemia virus type 1 (HTLV-1). Despite several investigations using
human specimens and mice models, the exact origin of ATL cells remains unclear.
Here we provide a new insight into the hierarchical architecture of ATL cells.
HTLV-1-infected cells and dominant ATL clones are successfully traced back to
CD45RA(+) T memory stem (TSCM) cells, which were recently identified as a unique
population with stemlike properties, despite the fact that the majority of ATL
cells are CD45RA(-)CD45RO(+) conventional memory T cells. TSCM cells from ATL
patients are capable of both sustaining themselves in less proliferative mode and
differentiating into other memory T-cell populations in the rapidly propagating
phase. In a xenograft model, a low number of TSCM cells efficiently repopulate
identical ATL clones and replenish downstream CD45RO(+) memory T cells, whereas
other populations have no such capacities. Taken together, these findings
demonstrate the phenotypic and functional heterogeneity and the hierarchy of ATL
cells. TSCM cells are identified as the hierarchical apex capable of
reconstituting identical ATL clones. Thus, this is the first report to
demonstrate the association of a T-cell malignancy with TSCM cells.
PMID- 25847016
TI - Comparative efficacy of nimesulide and ketoprofen on inflammatory events in third
molar surgery: a split-mouth, prospective, randomized, double-blind study.
AB - This study aimed to compare the effect of nimesulide and ketoprofen on
inflammatory parameters related to the surgical removal of third molars. A split
mouth, prospective, randomized, double-blind study was conducted in patients
undergoing removal of four third molars. Eighteen eligible patients were
allocated to one of two groups to receive treatment two times a day with either
ketoprofen 100 mg or nimesulide 100 mg for a period of 3 days. The rescue
medication intake (number) and pain intensity were evaluated at 6, 12, 24, and 48
h, and at 7 days postoperatively. Swelling and maximum mouth opening were
evaluated at 24 h, 72 h, and 7 days postoperatively. The peak pain score occurred
at 6h after surgery in the nimesulide group and at 12h in the ketoprofen group.
There was no statistically significant difference between the groups, although
pain relief was observed after 48 h in the nimesulide group and after 7 days in
the ketoprofen group. For each group, there was a statically significant
difference in pain scores among the studied periods (P<0.0001). None of the
patients required rescue medication. There was a statistically significant
difference in maximum mouth opening between the preoperative and postoperative
periods (P<0.0001). Ketoprofen and nimesulide were effective at controlling pain,
swelling, and trismus after the surgical removal of third molars.
PMID- 25847017
TI - B-cell-activating factor belonging to the tumor necrosis factor family (BAFF) and
a proliferation-inducing ligand (APRIL) levels in cerebrospinal fluid of patients
with meningoencephalitis.
AB - The B-cell-activating factor belonging to the tumor necrosis factor family (BAFF)
and a proliferation-inducing ligand (APRIL) are important factors for the
survival of transitional and mature B cells. High levels of BAFF and APRIL are
present in adults with several autoimmune diseases. However, there are few
reports about BAFF and APRIL levels in the cerebrospinal fluid (CSF) of patients
with meningoencephalitis. We evaluated BAFF and APRIL levels in CSF samples from
patients with viral meningitis (VM) (28 patients), autoimmune encephalitis (AE)
associated with antineuronal antibodies (15 patients), idiopathic normal pressure
hydrocephalus (iNPH) (11 patients), herpes simplex encephalitis (HSE) (9
patients), bacterial meningitis (BM) (6 patients), and cryptococcal meningitis
(CM) (4 patients). The CSF BAFF levels were significantly higher in patients with
HSE, BM, or VM than AE or iNPH, and significantly higher in patients with CM than
iNPH. The CSF APRIL levels were significantly higher in patients with HSE or BM
than AE, VM, or iNPH. Although this is a preliminary report due to within-group
variation and small sample size, the data suggest that CSF BAFF and APRIL levels
are increased in HSE and BM, but not AE.
PMID- 25847018
TI - Case report: A Chinese child with Andersen-Tawil syndrome due to a de novo KCNJ2
mutation.
PMID- 25847019
TI - Fragile X premutation carriers: A systematic review of neuroimaging findings.
AB - BACKGROUND: Expansion of the CGG repeat region of the FMR1 gene from less than 45
repeats to between 55 and 200 repeats is known as the fragile X premutation.
Carriers of the fragile X premutation may develop a neurodegenerative disease
called fragile X-associated tremor/ataxia syndrome (FXTAS). Recent evidence
suggests that premutation carriers experience other psychiatric difficulties
throughout their lifespan. METHODS: Medline, EMBASE and PsychINFO were searched
for all appropriate English language studies published between January 1990 and
December 2013. 419 potentially relevant articles were identified and screened. 19
articles were included in the analysis. RESULTS: We discuss key structural
magnetic resonance imaging (MRI) findings such as the MCP sign and white matter
atrophy. Additionally, we discuss how functional MRI results have progressed our
knowledge of how FXTAS may manifest, including reduced brain activation during
social and memory tasks in multiple regions. LIMITATIONS: This systematic review
may have been limited by the search for articles on just 3 scientific databases.
Differing techniques and methods of analyses between research groups and primary
research articles may have caused differences in results between studies.
CONCLUSION: Current MRI studies into the fragile X premutation have been
important in the diagnosis of FXTAS and identifying potential pathophysiological
mechanisms. Associations with blood based measures have also demonstrated that
neurodevelopmental and neurodegenerative aspects of the fragile X premutation
could be functionally and pathologically separate. Larger longitudinal studies
will be required to investigate these conclusions.
PMID- 25847020
TI - Acute ischemic strokes from small vessel vasculitis due to disseminated
histoplasmosis infection.
PMID- 25847021
TI - Use of failure mode, effect and criticality analysis to improve safety in the
medication administration process.
AB - RATIONALE, AIMS AND OBJECTIVES: To critically evaluate the causes of preventable
adverse drug events during the nurse medication administration process in
inpatient units with computerized prescription order entry and profiled automated
dispensing cabinets in order to prioritize interventions that need to be
implemented and to evaluate the impact of specific interventions on the
criticality index. METHODS: This is a failure mode, effects and criticality
analysis (FMECA) study. A multidisciplinary consensus committee composed of
pharmacists, nurses and doctors evaluated the process of administering
medications in a hospital setting in Spain. By analysing the process, all failure
modes were identified and criticality was determined by rating severity,
frequency and likelihood of failure detection on a scale of 1 to 10, using
adapted versions of already published scales. Safety strategies were identified
and prioritized. RESULTS: Through consensus, the committee identified eight
processes and 40 failure modes, of which 20 were classified as high risk. The sum
of the criticality indices was 5254. For the potential high-risk failure modes,
21 different potential causes were found resulting in 24 recommendations.
Thirteen recommendations were prioritized and developed over a 24-month period,
reducing total criticality from 5254 to 3572 (a 32.0% reduction). The
recommendations with a greater impact on criticality were the development of an
electronic medication administration record (-582) and the standardization of
intravenous drug compounding in the unit (-168). Other improvements, such as
barcode medication administration technology (-1033), were scheduled for a longer
period of time because of lower feasibility. CONCLUSION: FMECA is a useful
approach that can improve the medication administration process.
PMID- 25847022
TI - Serum pregnancy-associated plasma protein-A in the three trimesters of pregnancy:
effects of maternal characteristics and medical history.
AB - OBJECTIVE: To define the contribution of maternal variables which influence the
measured level of maternal serum pregnancy-associated plasma protein-A (PAPP-A)
in screening for pregnancy complications. METHODS: Maternal characteristics and
medical history were recorded and serum PAPP-A was measured in women with a
singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 +
6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies
delivering phenotypically normal live births or stillbirths >= 24 weeks'
gestation, variables from maternal demographic characteristics and medical
history that are important in the prediction of PAPP-A were determined from a
linear mixed-effects multiple regression. RESULTS: Serum PAPP-A was measured in
94,966 cases in the first trimester, 7785 in the second trimester and 8286 in the
third trimester. Significant independent contributions to serum PAPP-A were
provided by gestational age, maternal weight, height, racial origin, cigarette
smoking, diabetes mellitus, method of conception, previous pregnancy with or
without pre-eclampsia (PE) and birth-weight Z-score of the neonate in the
previous pregnancy. The effects of some variables were similar and those for
others differed in the three different trimesters. Random-effects multiple
regression analysis was used to define the contribution of maternal variables
that influence the measured level of serum PAPP-A and express the values as
multiples of the median (MoMs). The model was shown to provide an adequate fit of
MoM values for all covariates, both in pregnancies that developed PE and in those
without this pregnancy complication. CONCLUSIONS: A model was fitted to express
the measured serum PAPP-A across the three trimesters of pregnancy as MoMs, after
adjusting for variables from maternal characteristics and medical history that
affect this measurement.
PMID- 25847023
TI - Distinctive oncological features of stage IIIA colorectal cancer: Analysis of
prognostic factors for selective adjuvant chemotherapy.
AB - INTRODUCTION: In the seventh TNM classification, stage IIIA includes tumors with
early stage of bowel wall invasion and regional lymph node metastasis. We
investigated the validity of the current TNM classification of patients with
stage IIIA colorectal cancer and identified prognostic factors of them for
ameliorating treatment strategies for them. METHODS: This study included the
participation of four tertiary hospitals. A total of 4,236 patients with Stages I
IIIB colorectal cancer were analyzed. The primary end point was the 5-year
relapse-free survival. RESULTS: The 5-year relapse-free survival of patients with
stage IIIA disease was similar to that of patients with stage IIA. The 5-year
relapse-free survival was 88.9% in the chemotherapy group (n = 152) and 82.3% in
the no-chemotherapy group (n = 36, P = 0.111). Tumor differentiation (moderate or
poor) and venous invasion were independent prognostic factors of relapse-free
survival. CONCLUSIONS: The relapse-free survival of patients with stage IIIA
tumors was similar to that of patients with stage IIA tumors, and the prognosis
of stage IIIA tumors varied significantly by the tumor factors identified. These
factors can be used to predict the risk of disease recurrence and to optimize the
use of adjuvant chemotherapy.
PMID- 25847024
TI - Erythropoietin Promotes Neural Plasticity and Spatial Memory Recovery in Fimbria
Fornix-Lesioned Rats.
AB - BACKGROUND: Erythropoietin (EPO) upregulates the mitogen activated protein kinase
(MAPK) cascade, a central signaling pathway in cellular plastic mechanisms, and
is critical for normal brain development. OBJECTIVE: We hypothesized that EPO
could modulate the plasticity mechanisms supporting spatial memory recovery in
fimbria-fornix-transected animals. METHODS: Fimbria-fornix was transected in 3
groups of rats. Seven days later, EPO was injected daily for 4 consecutive days
within 10 minutes after training on a water maze task. RESULTS: Our results show
that EPO injections 10 minutes after training produced a substantial spatial
memory recovery in fimbria-fornix-lesioned animals. In contrast, an EPO injection
shortly after fimbria-fornix lesion surgery does not promote spatial-memory
recovery. Neither does daily EPO injection 5 hours after the water maze
performance. EPO, on the other hand, induced the expression of plasticity-related
genes like arc and bdnf, but this effect was independent of training or lesion.
CONCLUSIONS: This finding supports our working hypothesis that EPO can modulate
transient neuroplastic mechanisms triggered by training in lesioned animals.
Consequently, we propose that EPO administration can be a useful trophic factor
to promote neural restoration when given in combination with training.
PMID- 25847026
TI - About three cases of ulceroglandular tularemia, is this the re-emergence of
Francisella tularensis in Belgium?
AB - Tularemia is a zoonosis caused by Francisella tularensis that can be transmitted
by several ways to human being and cause different clinical manifestations. We
report three clinical cases of tularemia with ulceroglandular presentation in
young males acquired during outdoor activities in Southern Belgium. Confirmation
of the diagnosis was established by serology. Only three cases of tularemia have
been reported in Belgium between 1950 and 2012 by the National Reference
Laboratory CODA-CERVA (Ref Lab CODA-CERVA) but re-emergence of tularemia is
established in several European countries and F. tularensis is also well known to
be present in animal reservoirs and vectors in Belgium. The diagnosis of
tularemia has to be considered in case of suggestive clinical presentation
associated with epidemiological risk factors.
PMID- 25847025
TI - Chemoradiation therapy for rectal cancer in the distal rectum followed by organ
sparing transanal endoscopic microsurgery (CARTS study).
AB - BACKGROUND: This prospective multicentre study was performed to quantify the
number of patients with minimal residual disease (ypT0-1) after neoadjuvant
chemoradiotherapy and transanal endoscopic microsurgery (TEM) for rectal cancer.
METHODS: Patients with clinically staged T1-3 N0 distal rectal cancer were
treated with long-course chemoradiotherapy. Clinical response was evaluated 6-8
weeks later and TEM performed. Total mesorectal excision was advocated in
patients with residual disease (ypT2 or more). RESULTS: The clinical stage was
cT1 N0 in ten patients, cT2 N0 in 29 and cT3 N0 in 16 patients. Chemoradiotherapy
related complications of at least grade 3 occurred in 23 of 55 patients, with two
deaths from toxicity, and two patients did not have TEM or major surgery. Among
47 patients who had TEM, ypT0-1 disease was found in 30, ypT0 N1 in one, ypT2 in
15 and ypT3 in one. Local recurrence developed in three of the nine patients with
ypT2 tumours who declined further surgery. Postoperative complications grade I
IIIb occurred in 13 of 47 patients after TEM and in five of 12 after (completion)
surgery. After a median follow-up of 17 months, four local recurrences had
developed overall, three in patients with ypT2 and one with ypT1 disease.
CONCLUSION: TEM after chemoradiotherapy enabled organ preservation in one-half of
the patients with rectal cancer.
PMID- 25847027
TI - Biomedical applications of trastuzumab: as a therapeutic agent and a targeting
ligand.
AB - Trastuzumab (TZ) is a humanized monoclonal antibody targeted to the extracellular
domain of human epidermal growth factor receptor 2 (HER2), a tyrosine kinase
receptor. TZ is approved by the Food and Drug Administration (FDA) for the
treatment of HER2-overexpressing early stage and metastatic breast cancer and
HER2-overexpressing metastatic gastric cancer. For breast cancer, it is
recommended as both a single agent and in combination with standard chemotherapy.
In the last few years, TZ has also been used as a targeting ligand.
Overexpression of HER2 in breast cancer and the presence of free surface
functional groups on TZ provide an opportunity to use it as a targeting ligand.
TZ can be conjugated to various nanoparticulate systems such as dendrimers,
polymeric, and protein nanoparticles to target drug delivery. TZ-conjugated
inorganic nanoparticles have been reported for imaging and diagnostic purposes.
This review summarizes the applications of TZ both as a therapeutic agent and as
a targeting ligand.
PMID- 25847028
TI - Complete genome sequence of Haloarcula sp. CBA1115 isolated from non-purified
solar salts.
AB - Haloarcula sp. CBA1115, isolated from non-purified solar salts from South Korea,
is a halophilic archaeon belonging to the family Halobacteriaceae. Here, we
present the complete genome sequence of the strain Haloarcula sp. CBA1115
(4,225,046bp, with a G+C content of 61.98%), which is distributed over one
chromosome and five plasmids. A comparison of the genome sequence of Haloarcula
sp. CBA1115 with those of members of its closely related taxa showed that the
closest neighbor is Haloarcula hispanica Y27, a popular model organism for
archaeal studies. The strain was found to possess a number of genes predicted to
be involved in osmo-regulatory strategies and metal regulation, suggesting that
it might be useful for bioremediation in extreme environments.
PMID- 25847029
TI - Discovery of germline-related genes in Cephalochordate amphioxus: A genome wide
survey using genome annotation and transcriptome data.
AB - The generation of germline cells is a critical process in the reproduction of
multicellular organisms. Studies in animal models have identified a common
repertoire of genes that play essential roles in primordial germ cell (PGC)
formation. However, comparative studies also indicate that the timing and
regulation of this core genetic program vary considerably in different animals,
raising the intriguing questions regarding the evolution of PGC developmental
mechanisms in metazoans. Cephalochordates (commonly called amphioxus or
lancelets) represent one of the invertebrate chordate groups and can provide
important information about the evolution of developmental mechanisms in the
chordate lineage. In this study, we used genome and transcriptome data to
identify germline-related genes in two distantly related cephalochordate species,
Branchiostoma floridae and Asymmetron lucayanum. Branchiostoma and Asymmetron
diverged more than 120 MYA, and the most conspicuous difference between them is
their gonadal morphology. We used important germline developmental genes in
several model animals to search the amphioxus genome and transcriptome dataset
for conserved homologs. We also annotated the assembled transcriptome data using
Gene Ontology (GO) terms to facilitate the discovery of putative genes associated
with germ cell development and reproductive functions in amphioxus. We further
confirmed the expression of 14 genes in developing oocytes or mature eggs using
whole mount in situ hybridization, suggesting their potential functions in
amphioxus germ cell development. The results of this global survey provide a
useful resource for testing potential functions of candidate germline-related
genes in cephalochordates and for investigating differences in gonad
developmental mechanisms between Branchiostoma and Asymmetron species.
PMID- 25847030
TI - Microvesicles Derived From Human Mesenchymal Stem Cells Restore Alveolar Fluid
Clearance in Human Lungs Rejected for Transplantation.
AB - The need to increase the donor pool for lung transplantation is a major public
health issue. We previously found that administration of mesenchymal stem cells
"rehabilitated" marginal donor lungs rejected for transplantation using ex vivo
lung perfusion. However, the use of stem cells has some inherent limitation such
as the potential for tumor formation. In the current study, we hypothesized that
microvesicles, small anuclear membrane fragments constitutively released from
mesenchymal stem cells, may be a good alternative to using stem cells. Using our
well established ex vivo lung perfusion model, microvesicles derived from human
mesenchymal stem cells increased alveolar fluid clearance (i.e. ability to absorb
pulmonary edema fluid) in a dose-dependent manner, decreased lung weight gain
following perfusion and ventilation, and improved airway and hemodynamic
parameters compared to perfusion alone. Microvesicles derived from normal human
lung fibroblasts as a control had no effect. Co-administration of microvesicles
with anti-CD44 antibody attenuated these effects, suggesting a key role of the
CD44 receptor in the internalization of the microvesicles into the injured host
cell and its effect. In summary, microvesicles derived from human mesenchymal
stem cells were as effective as the parent mesenchymal stem cells in
rehabilitating marginal donor human lungs.
PMID- 25847048
TI - INITIAT-E.D.: Impact of timing of INITIation of Antibiotic Therapy on mortality
of patients presenting to an Emergency Department with sepsis.
AB - OBJECTIVES: To analyse the association between time from triage to administration
of initial antibiotics and mortality in all patients presenting with sepsis to a
tertiary hospital ED. METHODS: A retrospective review of patients presenting to
the ED with sepsis from January to December 2012 was conducted at Flinders
Medical Centre, South Australia. Outcome measures were: time elapsed from triage
to administration of initial antibiotic therapy and in-hospital mortality.
RESULTS: A total of 220 patients presented with sepsis, comprising 102 cases of
uncomplicated sepsis and 118 severe sepsis. The median time to antibiotic
administration was 3.5 h (interquartile range [IQR] 1.7-6.6) and in-hospital
mortality was 28.6% (95% CI 22.6-34.6%). There was no association observed
between delays to antibiotics and mortality in the total patient population. When
stratified by presenting severity, patients with severe sepsis demonstrated a
trend towards increased mortality when delays to antibiotics exceeded 6 h from
triage (HR = 2.25, 95% CI 0.91-5.59, P = 0.08) in comparison with <1 h.
Significant delays to antibiotic administration occurred when initial agents were
charted as a 'regular medicine' (9.4 h, IQR 5.1-16.6) in comparison with a 'once
only order' (3.4 h, IQR 1.7-6.7), P < 0.001. CONCLUSIONS: Early administration of
antibiotics specifically in patients with severe sepsis might be beneficial.
Further studies within the ED are warranted to establish the effect of delayed
antibiotics in a generalised sepsis cohort.
PMID- 25847031
TI - Social context of preterm delivery in France in 2011 and impact on short-term
health outcomes: the EPIPAGE 2 cohort study.
AB - BACKGROUND: Low socio-economic context increases the risk of preterm delivery and
may affect short-term outcomes in children born preterm. We described the social
context of preterm delivery in France in 2011 and compared it with the general
population of deliveries over the same period. We also studied how social context
influenced pregnancy and delivery characteristics in the preterm population, and
how it affected mortality and short-term morbidity in liveborn preterm children
(<35 weeks). METHODS: We created an individual socio-economic vulnerability
index, derived from multiple correspondence analysis based on maternal social
information in the French National Perinatal Survey (NPS-2010). Weighted
coordinates were applied to families from the EPIPAGE 2 study, a population-based
cohort of preterm infants born in 2011, to quantify the infant's exposure to
socio-economic vulnerability. Multivariable logistic models were used to relate
the socio-economic context to pregnancy and delivery characteristics, and to
assess its impact on short-term outcomes of the infants. RESULTS: Among mothers
of preterm infants, gestational age decreased as socio-economic conditions
worsened. In the most deprived group, women had more irregular pregnancy care, a
higher prevalence of infection during pregnancy, and a lower rate of antenatal
corticosteroid administration. The most deprived group was associated with a
higher risk of severe morbidity for the preterm neonates. CONCLUSION: Our results
emphasise the need for a large population-based surveillance system to identify
the most deprived mothers, and to propose appropriate follow-up and care to these
women and their infants in order to enhance long-term health.
PMID- 25847050
TI - Hydroxyurea lowers transcranial Doppler flow velocities in children with sickle
cell anaemia in a Nigerian cohort.
AB - BACKGROUND: Sickle cell anaemia (SCA) is the leading genetic disorder in Nigeria.
Elevated velocities >=170 cm/sec occur in about a third of Nigerian children with
SCA. Chronic blood transfusion for stroke prevention is faced with a myriad of
challenges in our practice. OBJECTIVES: To evaluate the effectiveness of
hydroxyurea (HU) in reducing flow velocities in a cohort of Nigerian children
with SCA and elevated velocities treated with HU. METHODS: An observational study
was carried out on a cohort of Nigerian children with SCA and elevated velocities
identified on routine transcranial Doppler (TCD) screening. HU was recommended in
those with TCD velocities >= 170cm/sec as stipulated in our hospital protocol.
Outcomes were compared after >=12 months of observation. RESULTS: Fifty children
with elevated TCD velocities were studied; 31 consented to HU therapy and 19
declined. Children on HU showed a statistically significant decline in mean
velocities from 199.7 [17.1] cm/sec to 165.8 [20.7] cm/sec (P < 0.001) with a
significant increase in mean packed cell volume from 21.1 [3.4] to 25.0 [2.8]%.
Children without treatment had a significant rise in mean velocities from 190.2
[10.8] cm/sec to 199.7 [14.9] cm/sec (P = 0.003). Children with conditional risk
velocities on HU were less likely to convert to abnormal risk (P < 0.001). Two
stroke events occurred, one in each group. No adverse effects of HU were recorded
in the cohort. CONCLUSION: HU appears to significantly reduce TCD velocities in
Nigerian children with SCA and elevated velocities >=170 cm/sec with beneficial
effect on the haematological profile. HU may provide an effective approach to
primary stroke prevention, particularly in Africa.
PMID- 25847051
TI - Disclosing discourses: biomedical and hospitality discourses in patient education
materials.
AB - Patient education materials have the potential to strengthen the health literacy
of patients. Previous studies indicate that readability and suitability may be
improved. The aim of this study was to explore and analyze discourses inherent in
patient education materials since analysis of discourses could illuminate values
and norms inherent in them. Clinics in Sweden that provided colorectal cancer
surgery allowed access to written information and 'welcome letters' sent to
patients. The material was analysed by means of discourse analysis, embedded in
Derrida's approach of deconstruction. The analysis revealed a biomedical
discourse and a hospitality discourse. In the biomedical discourse, the subject
position of the personnel was interpreted as the messenger of medical information
while that of the patients as the carrier of diagnoses and recipients of
biomedical information. In the hospitality discourse, the subject position of the
personnel was interpreted as hosts who invite and welcome the patients as guests.
The study highlights the need to eliminate paternalism and fosters a critical
reflective stance among professionals regarding power and paternalism inherent in
health care communication.
PMID- 25847052
TI - Knockdown of reticulon 4C by lentivirus inhibits human colorectal cancer cell
growth.
AB - Colorectal cancer is the third most common type of cancer worldwide with high
cell motility and metastatic potential. Reticulon 4C (RTN4-C) is the shortest
isoform of the reticulon family protein RTN4, which may act to induce cell
apoptosis and suppress tumor development. The aim of the present study was to
determine the role of RTN4-C in colorectal cancer, and potentially identify a
novel target for anti-tumor therapy. To investigate the biological role of RTN4-C
in colorectal cancer, the expression levels of RTN4-C were initially analyzed in
six colorectal cancer cell lines by reverse transcription-quantitative polymerase
chain reaction and western blot analysis. In addition, lentivirus-based RNA
interference was utilized to knock down RTN4-C expression in RKO and DLD-1 cells
with low and high levels of RTN4-C, respectively. The rate of proliferation
decreased in RTN4-C silenced RKO and DLD-1 cells compared with the control, as
determined using MTT and colony formation assays. Flow cytometric analysis
revealed that RTN4-C knockdown in RKO cells led to cell cycle arrest at the G0/G1
phase, particularly at the sub-G1 phase representing apoptotic cells. These
results indicate that RTN4-C has an important role in colorectal cancer cell
growth, which may provide a potential therapeutic approach for human colorectal
cancer.
PMID- 25847053
TI - First evidence of light-induced spin transition in molybdenum(IV).
AB - Photo-induced spin transition in a molybdenum-zinc complex has been evidenced and
fully characterized by Squid magnetometry and several spectroscopies performed
under irradiation (IR, EPR, etc.). The phenomenon has been confirmed by X-ray
diffraction and DFT calculations yielding a Light-Induced Excited Spin State
Trapping Effect (LIESST) on a 4d transition metal ion.
PMID- 25847054
TI - Effects and Moderators of a Short Theory of Mind Intervention for Children with
Autism Spectrum Disorder: A Randomized Controlled Trial.
AB - Limited perspective taking or "Theory of Mind" (ToM) abilities are a core deficit
of autism, and many interventions are aimed to improve ToM abilities. In this
study, we investigated the effectiveness of a ToM treatment for children with
autism spectrum disorders (ASD) and, for the first time, the moderating roles of
social interaction style (SIS) and disruptive behavior (DB), to determine which
children are most likely to respond to this intervention. The trial protocol is
registered at www.trialregister.nl, trial number 2327 and published before the
data collection was finished (www.trialsjournal.com). Children with autism aged 7
12 years (n = 97) were randomized over a waitlist control or a treatment
condition. Outcome measures included ToM and emotion understanding, parent and
teacher questionnaires on children's social skills, ToM-related social behavior,
and autistic traits. Six-month follow-up parent reported data were collected for
the treatment group. The treatment had a positive effect on ToM understanding,
parent-reported ToM behavior, and autistic traits, but not on parent or teacher
reported social behavior. Passive SIS was associated with diminished treatment
effects on autistic traits, but DB was unrelated to outcomes. The ToM
intervention improved conceptual social understanding and ToM-related behavior of
children with ASD. However, broader application of learned skills to other
domains of functioning was limited. Individual differences with regard to
treatment response are discussed.
PMID- 25847055
TI - Tetrahymena Expresses More than a Hundred Proteins with Lipid-binding MORN Motifs
that can Differ in their Subcellular Localisations.
AB - Proteins with membrane occupation and recognition nexus (MORN) motifs are
associated with cell fission in apicomplexan parasites, chloroplast division in
Arabidopsis and the motility of sperm cells. We found that ciliates are among
those that encode the largest variety of MORN proteins. Tetrahymena thermophila
expresses 129 MORN protein-encoding genes, some of which are specifically up
regulated during conjugation. A lipid-binding assay underpins the assumption that
the predominant function of MORN motifs themselves is to confer the ability of
lipid binding. The localisation of four MORN candidate proteins with similar
characteristics highlights the functional diversity of this group especially in
ciliates.
PMID- 25847056
TI - Sexual functioning and commitment to their current relationship among
breastfeeding and regularly cycling women in Manila, Philippines.
AB - This project investigates the relationship between lactation and female sexual
functioning and relationship commitment among partnered women in urban Manila.
Previous literature suggests that the time after giving birth is often rife with
lower sexual functioning and relationship dissatisfaction. Given the important
role of caregiving by multiple individuals in humans, the current cross-sectional
study suggests that female sexuality may decline immediately after giving birth
but then may increase afterwards. Non-cycling, breastfeeding (n = 86); cycling,
breastfeeding (n = 48); and nulliparous, regularly cycling (n = 105) women were
recruited from neighborhood health centers in Manila to complete questionnaires
that assessed sexual functioning and relationship satisfaction, along with
demographic variables. Cycling, breastfeeding women report the highest sexual
functioning scores and commitment scores. Females undergoing life history trade
offs between mating effort and parenting effort during the postpartum phase may
employ a strategy in which they continue investment both in their offspring and
in a romantic relationship. Variations in self-reported sexual functioning, level
of commitment in a relationship, and love toward her current partner may indicate
that breastfeeding women engage in sexual activities as part of a relationship
maintenance strategy. Cultural and life history factors will serve as a framework
for the findings. The current findings suggest women in Manila may experience a
post-birth increase in sexual functioning that may be higher than pre-pregnancy
levels. Future studies should incorporate a longitudinal component or a memory
recall on pre-pregnancy and post-birth sexual functioning levels.
PMID- 25847057
TI - Comparing Methods to Denote Treatment Outcome in Clinical Research and
Benchmarking Mental Health Care.
AB - Approaches based on continuous indicators (the size of the pre-to-post-test
change; effect size or DeltaT) and on categorical indicators (Percentage
Improvement and the Jacobson-Truax approach to Clinical Significance) are
evaluated to determine which has the best methodological and statistical
characteristics, and optimal performance, in comparing outcomes of treatment
providers. Performance is compared in two datasets from providers using the Brief
Symptom Inventory or the Outcome Questionnaire. Concordance of methods and their
suitability to rank providers is assessed. Outcome indicators tend to converge
and lead to a similar ranking of institutes within each dataset. Statistically
and conceptually, continuous outcome indicators are superior to categorical
outcomes as change scores have more statistical power and allow for a ranking of
providers at first glance. However, the Jacobson-Truax approach can complement
the change score approach as it presents outcome information in a clinically
meaningful manner. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONERS
MESSAGES: When comparing various indicators or treatment outcome, statistical
considerations designate continuous outcomes, such as the effect size of the pre
post change (effect size or DeltaT) as the optimal choice. Expressing outcome in
proportions of recovered, changed, unchanged or deteriorated patients has
supplementary value, as it is more easily interpreted and appreciated by
clinicians, managerial staff and, last but not the least, by patients. If
categorical outcomes are used with small datasets, true differences in
institutional performance may get obscured due to diminished power to detect
differences. With sufficient data, outcome according to continuous and
categorical indicators converge and lead to similar rankings of institutes'
performance.
PMID- 25847058
TI - Human lung microRNA profiling in pulmonary arterial hypertension secondary to
congenital heart defect.
AB - OBJECTIVE: Although several microRNAs were reported to play essential roles in
pulmonary artery hypertension due to hypoxia or monocrotaline, their potential
role in pulmonary arterial hypertension secondary to congenital heart disease is
largely unknown. This study aimed to indentify microRNAs implicated in pulmonary
arterial hypertension secondary to congenital heart disease in children. METHODS:
Using microRNAs microarray, we profiled the microRNAs in the lung specimen from
12 congenital heart disease patients, (6 with pulmonary arterial hypertension and
the others without). We validated the microRNAs expression using RT-PCR
experiments. Then, we predicted the target genes of the promising microRNAs by
bioinformatical analysis and verified its regulating role by luciferase assay and
western blot experiments. RESULTS: All the 12 patients were uneventfully
recovered from cardiac surgery. Comparing to the non-pulmonary arterial
hypertension lung tissue, 62 microRNAs were significantly up-regulated and 12
were significantly de-regulated in the pulmonary arterial hypertension lung
tissue. Among them 27 microRNAs reached P values <= 0.05, we validated the up
regulation of microRNA-27b by RT-PCR experiments and found the expression level
of microRNA-27b was correlated with preoperative mean pulmonary arterial
pressure. In vitro, overexpression of microRNA-27b decreased the protein
expression of NOTCH1 and significantly reduced luciferase activity. CONCLUSIONS:
The current study revealed for the first time that microRNAs may be important
regulators in pulmonary arterial hypertension secondary to congenital heart
disease, and demonstrated the correlation between microRNA-27b and pulmonary
arterial hypertension with the implication of NOTCH1.
PMID- 25847059
TI - Diabetes self-management education is not associated with a reduction in long
term diabetes complications: an effectiveness study in an elderly population.
AB - RATIONALE, AIMS AND OBJECTIVES: The efficacy of diabetes self-management
education on glycaemic control, self-care behaviour and knowledge has been
established by short-term studies in experimental settings. The objective of this
study was to assess its effectiveness to improve quality of care and reduce the
risk of long-term diabetes complications in unselected older patients with
recently diagnosed diabetes in routine clinical care. METHODS: Using population
level health care administrative databases and registries, all patients aged >=66
years in Ontario, Canada with diabetes for <5 years were identified. Self
management education programme attendees (n = 8485) in 2006 were matched with non
attendees using high-dimensional propensity scores, creating extremely well
balanced study arms. Quality of care measures and the long-term risk of diabetes
complications were compared. RESULTS: Self-management programme attendees were
more likely than non-attendees to achieve process measures of quality of care
such as retinal screening examinations (75.3% versus 70.3%, adjusted relative
risk 1.05, 99% confidence interval 1.03-1.08), and >=2 glycated haemoglobin tests
(57.5% versus 53.3%, adjusted relative risk 1.08, 99% confidence interval 1.05
1.11). However, with a median follow-up of 5.3 years, diabetes complications and
mortality were not different between arms. CONCLUSIONS: In real-world clinical
care, self-management education for older patients with recently diagnosed
diabetes was associated with modest improvements in quality of care, but no
reductions in long-term clinical events.
PMID- 25847060
TI - Disruption of cardiogenesis in human embryonic stem cells exposed to
trichloroethylene.
AB - Trichloroethylene (TCE) is ubiquitous in our living environment, and prenatal
exposure to TCE is reported to cause congenital heart disease in humans. Although
multiple studies have been performed using animal models, they have limited value
in predicting effects on humans due to the unknown species-specific toxicological
effects. To test whether exposure to low doses of TCE induces developmental
toxicity in humans, we investigated the effect of TCE on human embryonic stem
cells (hESCs) and cardiomyocytes (derived from the hESCs). In the current study,
hESCs cardiac differentiation was achieved by using differentiation medium
consisting of StemPro-34. We examined the effects of TCE on cell viability by
cell growth assay and cardiac inhibition by analysis of spontaneously beating
cluster. The expression levels of genes associated with cardiac differentiation
and Ca2+ channel pathways were measured by immunofluorescence and qPCR. The
overall data indicated the following: (1) significant cardiac inhibition, which
was characterized by decreased beating clusters and beating rates, following
treatment with low doses of TCE; (2) significant up-regulation of the
Nkx2.5/Hand1 gene in cardiac progenitors and down regulation of the Mhc-7/cTnT
gene in cardiac cells; and (3) significant interference with Ca2+ channel
pathways in cardiomyocytes, which contributes to the adverse effect of TCE on
cardiac differentiation during early embryo development. Our results confirmed
the involvement of Ca2+ turnover network in TCE cardiotoxicity as reported in
animal models, while the inhibition effect of TCE on the transition of cardiac
progenitors to cardiomyocytes is unique to hESCs, indicating a species-specific
effect of TCE on heart development. This study provides new insight into TCE
biology in humans, which may help explain the development of congenital heart
defects after TCE exposure. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31:
1372-1380, 2016.
PMID- 25847061
TI - The stress of growing old: sex- and season-specific effects of age on allostatic
load in wild grey mouse lemurs.
AB - Chronic stress [i.e. long-term elevation of glucocorticoid (GC) levels] and aging
have similar, negative effects on the functioning of an organism. Aged
individuals' declining ability to regulate GC levels may therefore impair their
ability to cope with stress, as found in humans. The coping of aged animals with
long-term natural stressors is virtually unstudied, even though the ability to
respond appropriately to stressors is likely integral to the reproduction and
survival of wild animals. To assess the effect of age on coping with naturally
fluctuating energetic demands, we measured stress hormone output via GC
metabolites in faecal samples (fGCM) of wild grey mouse lemurs (Microcebus
murinus) in different ecological seasons. Aged individuals were expected to
exhibit elevated fGCM levels under energetically demanding conditions. In line
with this prediction, we found a positive age effect in the dry season, when food
and water availability are low and mating takes place, suggesting impaired coping
of aged wild animals. The age effect was significantly stronger in females, the
longer-lived sex. Body mass of males but not females correlated positively with
fGCM in the dry season. Age or body mass did not influence fGCM significantly in
the rainy season. The sex- and season-specific predictors of fGCM may reflect the
differential investment of males and females into reproduction and longevity. A
review of prior research indicates contradictory aging patterns in GC regulation
across and even within species. The context of sampling may influence the
likelihood of detecting senescent declines in GC functioning.
PMID- 25847062
TI - Toward predicting metastatic progression of melanoma based on gene expression
data.
AB - Primary and metastatic melanoma tumors share the same cell origin, making it
challenging to identify genomic biomarkers that can differentiate them. Primary
tumors themselves can be heterogeneous, reflecting ongoing genomic changes as
they progress toward metastasizing. We developed a computational method to
explore this heterogeneity and to predict metastatic progression of the primary
tumors. We applied our method separately to gene expression and to microRNA
(miRNA) expression data from ~450 primary and metastatic skin cutaneous melanoma
(SKCM) samples from the Cancer Genome Atlas (TCGA). Metastatic progression scores
from RNA-seq data were significantly associated with clinical staging of
patients' lymph nodes, whereas scores from miRNA-seq data were significantly
associated with Clark's level. The loss of expression of many characteristic
epithelial lineage genes in primary SKCM tumor samples was highly correlated with
predicted progression scores. We suggest that those genes/miRNAs might serve as
putative biomarkers for SKCM metastatic progression.
PMID- 25847063
TI - Evaluation of the efficacy and safety of combinations of hydroquinone, glycolic
acid, and hyaluronic acid in the treatment of melasma.
AB - BACKGROUND: Various treatments are currently available for melasma. However,
results are often disappointing. OBJECTIVES: 1 To assess the efficacy and safety
of combinations of hydroquinone, glycolic acid, and hyaluronic acid in the
treatment of melasma after topical application. 2 To evaluate the dermoscopy as a
tool in diagnosis and follow-up of melasma treatment. PATIENTS AND METHODS: One
hundred patients with mild, moderate-to-severe melasma were divided into five
groups. Group I (twenty patients were treated with cream formula containing 4%
hydroquinone), group II (twenty patients were treated with cream formula
containing 4% hydroquinone + 10% glycolic acid), group III (twenty patients were
treated with cream formula containing 4% hydroquinone + 0.01% hyaluronic acid),
group IV (twenty patients were treated with cream formula containing 4%
hydroquinone + 10% glycolic acid + 0.01% hyaluronic acid), and group V (twenty
patients were treated with placebo cream). All patients were subjected to
dermoscopic examination and digital photographs before and after treatment. The
response and side effects were evaluated. RESULTS: Groups I, III, and IV showed
highly significant changes in modified Melasma Area and Severity Index (mMASI)
score after using the treatment. Group II showed significant change in mMASI
score after using the treatment. The side effects were more reported in group II,
followed by group IV, followed by group I, followed by group III. There was
highly significant difference between the dermoscopic color findings before and
after treatment. Vascularization was another dermoscopic finding. CONCLUSION: A
cream formula containing 4% hydroquinone + 10% glycolic acid + 0.01% hyaluronic
acid was very effective in treatment of melasma with tolerable side effects.
Dermoscope is a valuable noninvasive tool in the diagnosis and follow-up of
melasma treatment.
PMID- 25847064
TI - The influence of teacher feedback on children's perceptions of student-teacher
relationships.
AB - BACKGROUND: Teachers can deliver feedback using person ('you are clever') or
process terms ('you worked hard'). Person feedback can lead to negative academic
outcomes, but there is little experimental research examining the impact of
feedback on children's perceptions of the student-teacher relationship. AIM: We
examined the effects of person, process, and no feedback on children's
perceptions of their relationship with a (fictional) teacher following success
and failure. SAMPLES: Participants were British children (145 aged 9-11 in
experiment 1 and 98 aged 7-11 in experiment 2). METHOD: In experiment 1,
participants read three scenarios where they succeeded and received one of two
types of praise (person or process) or no praise. Participants then read two
scenarios where they failed. In experiment 2, participants read that they had
failed in three tasks and received one of two types of criticism (person or
process) or no criticism. Participants then read two scenarios where they
succeeded. They rated how much they liked the teacher and how much they felt that
the teacher liked them. RESULTS: Children felt more positive about the student
teacher relationship following success than failure. Type of praise did not
influence perceptions of the student-teacher relationship following success or
failure. However, person criticism led children to view the student-teacher
relationship more negatively following failure and maintain this negative view
following the first success. CONCLUSIONS: Success appears to be important for
developing positive student-teacher relationships. In response to failure,
teachers could avoid person criticism which may negatively influence the student
teacher relationship.
PMID- 25847065
TI - The camKK2/camKIV relay is an essential regulator of hepatic cancer.
AB - Hepatic cancer is one of the most lethal cancers worldwide. Here, we report that
the expression of Ca(2+) /calmodulin-dependent protein kinase kinase 2 (CaMKK2)
is significantly up-regulated in hepatocellular carcinoma (HCC) and negatively
correlated with HCC patient survival. The CaMKK2 protein is highly expressed in
all eight hepatic cancer cell lines evaluated and is markedly up-regulated
relative to normal primary hepatocytes. Loss of CaMKK2 function is sufficient to
inhibit liver cancer cell growth, and the growth defect resulting from loss of
CaMKK2 can be rescued by ectopic expression of wild-type CaMKK2 but not by kinase
inactive mutants. Cellular ablation of CaMKK2 using RNA interference yields a
gene signature that correlates with improvement in HCC patient survival, and
ablation or pharmacological inhibition of CaMKK2 with STO-609 impairs
tumorigenicity of liver cancer cells in vivo. Moreover, CaMKK2 expression is up
regulated in a time-dependent manner in a carcinogen-induced HCC mouse model, and
STO-609 treatment regresses hepatic tumor burden in this model. Mechanistically,
CaMKK2 signals through Ca(2+) /calmodulin-dependent protein kinase 4 (CaMKIV) to
control liver cancer cell growth. Further analysis revealed that CaMKK2 serves as
a scaffold to assemble CaMKIV with key components of the mammalian target of
rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway and thereby stimulate
protein synthesis through protein phosphorylation. CONCLUSION: The CaMKK2/CaMKIV
relay is an upstream regulator of the oncogenic mammalian target of
rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway, and the importance of
this CaMKK2/CaMKIV axis in HCC growth is confirmed by the potent growth
inhibitory effects of genetically or pharmacologically decreasing CaMKK2
activity; collectively, these findings suggest that CaMKK2 and CaMKIV may
represent potential targets for hepatic cancer.
PMID- 25847067
TI - Catecholaminergic contributions to vocal communication signals.
AB - Social context affects behavioral displays across a variety of species. For
example, social context acutely influences the acoustic and temporal structure of
vocal communication signals such as speech and birdsong. Despite the prevalence
and importance of such social influences, little is known about the neural
mechanisms underlying the social modulation of communication. Catecholamines are
implicated in the regulation of social behavior and motor control, but the degree
to which catecholamines influence vocal communication signals remains largely
unknown. Using a songbird, the Bengalese finch, we examined the extent to which
the social context in which song is produced affected immediate early gene
expression (EGR-1) in catecholamine-synthesising neurons in the midbrain.
Further, we assessed the degree to which administration of amphetamine, which
increases catecholamine concentrations in the brain, mimicked the effect of
social context on vocal signals. We found that significantly more
catecholaminergic neurons in the ventral tegmental area and substantia nigra (but
not the central grey, locus coeruleus or subcoeruleus) expressed EGR-1 in birds
that were exposed to females and produced courtship song than in birds that
produced non-courtship song in isolation. Furthermore, we found that amphetamine
administration mimicked the effects of social context and caused many aspects of
non-courtship song to resemble courtship song. Specifically, amphetamine
increased the stereotypy of syllable structure and sequencing, the repetition of
vocal elements and the degree of sequence completions. Taken together, these data
highlight the conserved role of catecholamines in vocal communication across
species, including songbirds and humans.
PMID- 25847066
TI - Effect of beta-anhydroicaritin on the expression levels of tumor necrosis factor
alpha and matrix metalloproteinase-3 in periodontal tissue of diabetic rats.
AB - The present study aimed to investigate the effect of beta-anhydroicaritin on the
expression levels of tumor necrosis factor (TNF)-alpha and matrix
metalloproteinase (MMP)-3, and the pathological changes in the periodontal tissue
of diabetic rats. Male Wistar rats (n=40; three months old) were randomly divided
into four groups: Normal control group, diabetes group, diabetes + beta
anhydroicaritin group and diabetes + urate group, (n=10 in each group). Following
an overnight fast, diabetes was induced by intraperitoneal injection of
streptozocin. The rats were maintained for 12 weeks and the blood sugar, urine
sugar and body weight were assessed in week 12. Histological changes of the
periodontal tissues were observed by hematoxylin and eosin staining, and the
expression levels of TNF-alpha and MMP-3 were observed by immunohistochemistry.
Following 12 weeks, the TNF-alpha grey value in the diabetes group was
significantly lower compared with that in the control group (P<0.05), while no
significant difference was observed between TNF-alpha levels in the diabetes +
beta-anhydroicaritin group, diabetes + urate group and the control group
(P>0.05). However, TNF-alpha levels in the diabetes + beta-anhdroicaritin group
and diabetes + urate group were significantly higher compared with those in the
diabetes group (P<0.05), and those in the diabetes + beta-anhydroicaritin group
were lower compared with those in the diabetes + urate group (P<0.05). The MMP-3
grey value in the diabetes group was significantly lower compared with that in
the control group (P<0.05), while no significant difference was observed between
MMP-3 levels in the diabetes + beta-anhydroicaritin group, diabetes + urate group
and the control group (P>0.05). However, MMP-3 levels the diabetes + beta
anhydroicaritin group and diabetes + urate group were significantly higher
compared with those in the diabetes group (P<0.05), and those in the diabetes +
beta-anhydroicaritin group were lower compared with those in the diabetes + urate
group (P<0.01). beta-anhydroicaritin normalized the expression levels of TNF
alpha and MMP-3 in the periodontal tissue of diabetic rats and led to the
recovery of the changes in the morphological structure of the periodontal tissue.
PMID- 25847068
TI - Occurrence of periodontal pathogens in ethnic groups from a native Brazilian
reservation.
AB - OBJECTIVE: The present study was designed to evaluate the occurrence of
periodontal pathogens in the subgingival biofilm of 100 native Brazilians living
at the Umutina Indian Reservation, Mato Grosso State, Brazil. METHODS:
Periodontal clinical examinations were carried out prior to collection of
subgingival biofilm, and the presence of 14 periodontal microorganisms was
evaluated by polymerase chain reaction (PCR). The prevalence and risk analysis
was performed using Cochran and Mantel-Haenszel statistics for dichotomous
variables or Pearson's chi-squared test for analysis of proportions when
variables had three or more categories. The interrelations between clinical and
microbiological parameters were assessed using Fisher's exact test and the Mann
Whitney U test. RESULTS: Individuals with chronic periodontitis were frequently
colonized by the association between Porphyromonas gingivalis and Campylobacter
rectus, P. gingivalis and Prevotella intermedia, or P. gingivalis and Tannerella
forsythia. Patients with chronic periodontitis were also colonized by
Porphyromonas gulae and P. intermedia or by the association between P. gulae and
T. forsythia. P. gulae was detected only in the subgingival samples from natives
on a traditional diet. Gingival bleeding was associated with Aggregatibacter
actinomycetemcomitans, Fusobacterium nucleatum, T. forsythia, P. gingivalis, P.
gulae, Porphyromonas endodontalis, P. intermedia, and Prevotella nigrescens.
Treponema denticola was uncommon. CONCLUSIONS: Peculiar microbiota was
demonstrated to be associated with different periodontal disease statuses in
native Brazilians, with modest occurrence of certain pathogens, such as T.
denticola, and the presence of P. gulae in natives with gingivitis or chronic
periodontitis.
PMID- 25847070
TI - Balo-like lesion associated with psoriasis and chronic autoimmune thyroiditis.
PMID- 25847069
TI - Effects of aging on evoked retrusive tongue actions.
AB - OBJECTIVE: Tongue strength, timing, and coordination deficits may underlie age
related swallowing function. Retrusive tongue actions are likely important in
retrograde bolus transport. However, age-related changes in retrusive tongue
muscle contractile properties have not been identified in animal studies. Because
previous studies employed whole hypoglossal nerve stimulation that activated both
protrusive and retrusive tongue muscles, co-contraction may have masked retrusive
muscle force decrements. The hypotheses of this study were: (1) retrusive tongue
muscle contraction forces would be diminished and temporal characteristics
prolonged in old rats when lateral nerves were selectively activated, and (2)
greater muscle contractile forces with selective lateral branch stimulation would
be found relative to whole hypoglossal nerve stimulation. DESIGN: Nineteen
Fischer 344/Brown Norway rats (9 old, 10 young adult) underwent tongue muscle
contractile property recording elicited by: (1) bilateral whole hypoglossal nerve
stimulation, and (2) selective lateral branch stimulation. Twitch contraction
time (CT), half-decay time, maximal twitch and tetanic forces, and a fatigue
index were measured. RESULTS: For whole nerve stimulation, CT was significantly
longer in the old group. No significant age group differences were found with
selective lateral nerve stimulation. Significantly reduced twitch forces (old
group only), increased tetanic forces and significantly less fatigue were found
with selective lateral nerve stimulation than with whole hypoglossal stimulation.
CONCLUSIONS: Retrusive tongue forces are not impaired in old rats. Deficits
observed in swallowing with aging may be due to other factors such as inadequate
bolus propulsive forces, mediated by protrusive tongue muscles, or
timing/coordination of muscle actions.
PMID- 25847071
TI - Short Stature Screening by Accurate Length Measurement in Infants with a Birth
Weight <9th Centile.
AB - BACKGROUND/AIMS: Intrauterine growth restriction is an indication for growth
hormone treatment. Birth length (BL) is needed to evaluate the influence of birth
size on childhood short stature. However, BL is commonly measured only
approximately, if at all. A single-centre study was undertaken to determine the
value of measuring accurate and targeted BL and parental height (PH) for neonates
with a birth weight (BW) <=9th centile, identifying short [BL <=-2 standard
deviation scores (SDS)] and light newborns (BW <=-2 SDS), and remeasuring short
neonates at 2 years in order to detect those not showing catch-up growth.
METHODS: Information was collected on all live births (n = 3,798) in a single
maternity unit during a 1-year period. RESULTS: BW was <=9th centile in 481
neonates (12.7%) of whom 47 were light but not short, 46 were short, and 60 were
both light and short. Of 107 eligible infants, 57 (53%) attended the 2-year
follow-up; failure of catch-up growth was identified in 6 infants (11%) of whom
only 1 was already known to medical services. PH was measured in both parents of
52/153 (34%) light and/or short infants. CONCLUSION: Targeted and accurate BL
measurement in newborns with a BW <=9th centile is a promising alternative to the
current practices. The feasibility of PH measurement after birth still requires
further evaluation. (c) 2015 S. Karger AG, Basel.
PMID- 25847074
TI - Effect of Filling Type and Heating Method on Prevalence of Listeria species and
Listeria monocytogenes in Dumplings Produced in Poland.
AB - The count of Listeria monocytogenes was determined, before and after heat
treatment, in 200 samples of dumplings of 9 brands and with different types of
stuffing. Analyses were conducted according to ISO 11290-1 standard and with real
time PCR method. The highest count of L. monocytogenes was found in meat
dumplings (10(2) to 10(4) CFU/g), whereas products with white cheese-potato
stuffing and vegetable-mushroom stuffing contained significantly less Listeria,
20 to 80 and 5 to 32 CFU/g, respectively. In cooled meat dumplings the extent of
contamination depended significantly on the producer. In addition, a significant
(P < 0.05) correlation was determined between contamination level and meat
content in the stuffing (rho = 0.418), especially in stuffing containing pork
meat (0.464), contrary to beef-containing stuffing (0.284). Heating dumplings in
boiling water for 2 min completely eliminated L. monocytogenes in meat dumplings.
In contrast, the microwave heating applied for 2 min at 600 W only reduced the
count of L. monocytogenes by 1 to 2 logs. Hence, the microwave heating failed to
reduce the risk of infection with this pathogen below the level permissible in
the EU regulation, especially in the most contaminated samples. In this case, the
efficacy of microwave heating was significantly (P < 0.05) affected by the
initial count of L. monocytogenes (rho = 0.626), then by meat content in the
stuffing (0.476), and to the lowest extent--by the type of meat (0.415 to 0.425).
However, no Listeria sp. and L. monocytogenes were isolated from cooked dumplings
with fruits (strawberries or blueberries).
PMID- 25847072
TI - Roles of the lateral fenestration residues of the P2X4 receptor that contribute
to the channel function and the deactivation effect of ivermectin.
AB - P2X receptors are cation-permeable ion channels gated by extracellular adenosine
triphosphate (ATP). Available crystallographic data suggest that ATP-binding
ectodomain is connected to the transmembrane pore domain by three structurally
conserved linker regions, which additionally frame the lateral fenestrations
through which permeating ions enter the channel pore. The role of these linker
regions in relaying the conformational change evoked by ATP binding of the
ectodomain to the pore-forming transmembrane domain has not been investigated
systematically. Using P2X4R as our model, we employed alanine and serine
replacement mutagenesis to determine how the side chain structure of these linker
regions influences gating. The mutants Y54A/S, F198A/S, and W259A/S all
trafficked normally to the plasma membrane of transfected HEK293 cells but were
poorly responsive to ATP. Nevertheless, the function of the F198A/S mutants could
be recovered by pretreatment with the known positive allosteric modulator of
P2X4R, ivermectin (IVM), although the IVM sensitivity of this mutant was
significantly impaired relative to wild type. The functional mutants Y195A/S,
F200A/S, and F330A/S exhibited ATP sensitivities identical to wild type,
consistent with these side chains playing no role in ATP binding. However,
Y195A/S, F200A/S, and F330A/S all displayed markedly changed sensitivity to the
specific effects of IVM on current deactivation, suggesting that these positions
influence allosteric modulation of gating. Taken together, our data indicate that
conserved amino acids within the regions linking the ectodomain with the pore
forming transmembrane domain meaningfully contribute to signal transduction and
channel gating in P2X receptors.
PMID- 25847073
TI - The vesicular nucleotide transporter (VNUT) is involved in the extracellular ATP
effect on neuronal differentiation.
AB - Before being released, nucleotides are stored in secretory vesicles through the
vesicular nucleotide transporter (VNUT). Once released, extracellular ATP
participates in neuronal differentiation processes. Thus, the expression of a
functional VNUT could be an additional component of the purinergic system which
regulates neuronal differentiation and axonal elongation. In vitro expression of
VNUT decreases neuritogenesis in N2a cells differentiated by retinoic acid
treatment, whereas silencing of VNUT expression increases the number and length
of neurites in these cells. These results highlight the role of VNUT in the
neuritogenic process because this transporter regulates the ATP content in
neurosecretory vesicles.
PMID- 25847075
TI - Vemurafenib/dabrafenib and trametinib.
PMID- 25847076
TI - Education and evaluation for the development of a qualified psychiatrist: Report
of the Teachers of Psychiatry meeting - Shanghai.
PMID- 25847077
TI - Effects on Physical Health of a Multicomponent Programme for Overweight and
Obesity for Adults with Intellectual Disabilities.
AB - BACKGROUND: Overweight and obesity are major health risk factors in people with
intellectual disabilities. The aim of this study was to test the effectiveness of
a multicomponent programme (physical activity, diet and motivation) for
overweight and obesity in adults with intellectual disabilities. MATERIAL AND
METHODS: A quasi-experimental design with repeated-measures and non-equivalent
control group (n = 33, n = 31) was used. The programme was conducted over 17
weeks, with follow-up at 6 months in a sample of Spanish adults with a mild and
moderate intellectual disability from a community occupational day centre, aged
from 23 to 50, 40.6% of which were women. RESULTS: A significant reduction in
weight and diastolic blood pressure was obtained over time, and this reduction
was maintained in the follow-up for weight. Reduction in heart rate was only
marginally significant. CONCLUSIONS: The treatment was effective in reducing
overweight and obesity, improving cardiovascular capacity and therefore the
physical health of the participants.
PMID- 25847078
TI - Sociodemographic characteristics and attitudes towards motherhood among single
women compared with cohabiting women treated with donor semen - a Danish
multicenter study.
AB - OBJECTIVE: To examine sociodemographic characteristics, family backgrounds,
reproductive histories, and attitudes towards motherhood in single vs. cohabiting
women seeking treatment with donor semen. DESIGN: Baseline data collection in a
multicenter cohort study. SETTING: All nine public fertility clinics in Denmark.
SAMPLE: In total n = 311 childless women initiating assisted reproduction using
donor semen. METHODS: Self-reported questionnaire responses from n = 184 single
women seeking treatment by using donor semen were compared with responses from n
= 127 cohabiting women. MAIN OUTCOME MEASURES: Sociodemographic characteristics,
family backgrounds, reproductive histories, attitudes towards motherhood.
RESULTS: Single women were 3.5 years older on average when initiating treatment
compared with cohabiting women. No significant differences were found regarding
sociodemographic characteristics, previous long-term relationships, previous
pregnancies, or attitudes towards motherhood between single women and cohabiting
women. The vast majority of single women wanted to achieve parenthood with a
partner, 85.8% wished to have a partner in the future, and approximately half of
them preferred for a partner to take parental responsibilities. CONCLUSIONS: In
this study single women seeking treatment with donor semen in the public health
system did not differ from cohabiting women, except that they were older. To be a
single mother by choice is not their preferred way of parenthood, but a solution
they needed to accept.
PMID- 25847079
TI - P,O-Phosphinophenolate zinc(II) species: synthesis, structure and use in the ring
opening polymerization (ROP) of lactide, epsilon-caprolactone and trimethylene
carbonate.
AB - The P,O-type phosphinophenol proligands (1.H, 2-PPh2-4-Me-6-Me-C6H2OH; 2.H, 2
PPh2-4-Me-6-(t)Bu-C6H2OH) readily react with one equiv. of ZnEt2 to afford in
high yields the corresponding Zn(II)-ethyl dimers of the type [(kappa(2)-P,O)Zn
Et]2 (3 and 4) with two MU-OPh bridging oxygens connecting the two Zn(II)
centers, as determined by X-ray diffraction (XRD) studies in the case of 3. Based
on diffusion-ordered NMR spectroscopy (DOSY), both species 3 and 4 retain their
dimeric structures in solution. The alcoholysis reaction of Zn(II) alkyls 3 and 4
with BnOH led to the high yield formation of the corresponding Zn(II) benzyloxide
species [(kappa(2)-P,O)Zn-OBn]2 (5 and 6), isolated in a pure form as colorless
solids. The centrosymmetric and dimeric nature of Zn(II) alkoxides 5 and 6 in
solution was deduced from DOSY NMR experiments and multinuclear NMR data. Though
the heteroleptic species 5 is stable in solution, its analogue 6 is instable in
CH2Cl2 solution at room temperature to slowly decompose to the corresponding
homoleptic species 8via the transient formation of (kappa(2)-P,O)2Zn2(MU-OBn)(MU
kappa(1):kappa(1)-P,O) (6'). Crystallization of compound 6 led to crystals of 6',
as established by XRD analysis. The reaction of ZnEt2 with two equiv. of 1.H and
2.H allowed access to the corresponding homoleptic species of the type [Zn(P,O)2]
(7 and 8). All gathered data are consistent with compound 7 being a dinuclear
species in the solid state and in solution. Data for species 8, which bears a
sterically demanding P,O-ligand, are consistent with a mononuclear species in
solution. The Zn(II) alkoxide species 5 and the [Zn(P,O)2]-type compounds 7 and 8
were evaluated as initiators of the ring-opening polymerization (ROP) of lactide
(LA), epsilon-caprolactone (epsilon-CL) and trimethylene carbonate (TMC). Species
5 is a well-behaved ROP initiator for the homo-, co- and ter-polymerization of
all three monomers with the production of narrow disperse materials under living
and immortal conditions. Though species 7 and 8 are ROP inactive on their own,
they readily polymerize LA in the presence of a nucleophile such as BnOH to
produce narrow disperse PLA, presumably via an activated-monomer ROP mechanism.
PMID- 25847080
TI - miR-204-5p promotes the adipogenic differentiation of human adipose-derived
mesenchymal stem cells by modulating DVL3 expression and suppressing Wnt/beta
catenin signaling.
AB - MicroRNAs (miRNAs or miRs) play an important regulatory role during adipogenesis,
and have been studied extensively in this regard. Specifically, the switch
between the differentiation of mesenchymal stem cells (MSCs) towards adipogenic
vs. osteogenic lineages is regulated by miR-204 which controls the expression of
Runx2. However, the association between miR-204-5p and the Wnt/beta-catenin
signaling pathway during adipogenesis has not yet been clarified. In the present
study, we demonstrate that miR-204-5p regulates the in vitro adipogenesis of
human adipose-derived mesenchymal stem cells (hADSCs). The level of miR-204-5p
was shown to be gradually upregulated during adipocytic differentiation, together
with the mRNA expression of the critical adipogenic transcription factors,
cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein
alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma
(PPARgamma), and the mature adipogenic marker, fatty acid binding protein 4
(FABP4). We further demonstrate that while the overexpression of miR-204-5p
promotes adipogenesis, its knockdown causes the inhibition of this process. We
then used bioinformatics tools and luciferase reporter assay to establish that
dishevelled segment polarity protein 3 (DVL3), a key regulator of the Wnt/beta
catenin signaling pathway, is a direct target of miR-204-5p. In addition, the
overexpression of DVL3 led to an increase in beta-catenin and cyclin D1 (CCND1)
expression and, by contrast, the knockdown of DVL3 led to a decrease in the
expression of beta-catenin and CCND1. The knockdown of DVL3 significantly
promoted adipogenesis. Finally, we demonstrated that the overexpression of miR
204-5p induced the downregulation of beta-catenin and the canonical Wnt target
gene, CCND1, in mature adipoctyes, while its knockdown led to their upregulation.
Taken together, our data suggest that miR-204-5p regulates adipogenesis by
controlling DVL3 expression and subsequently inhibiting the activation of the
Wnt/beta-catenin signaling pathway.
PMID- 25847081
TI - Pharmacokinetics of intra-articular betamethasone sodium phosphate and
betamethasone acetate and endogenous hydrocortisone suppression in exercising
horses.
AB - To the date, no reports exist of the pharmacokinetics (PK) of betamethasone (BTM)
sodium phosphate and betamethasone acetate administered intra-articular (IA) into
multiple joints in exercising horses. The purpose of the study was to determine
the PK of BTM and HYD concentrations in plasma and urine after IA administration
of a total of 30 mg BTM. Eight 4 years old Thoroughbred mares were exercised on a
treadmill and BTM was administered IA. Plasma and urine BTM and HYD were
determined via high performance liquid chromatography spectrometry for 6 weeks.
Concentration-time profiles of BTM and HYD in plasma and urine were used to
generate PK estimates for non-compartmental analyses and comparisons among times
and HYD concentrations. BTM in plasma had greater Tmax (Tmax 0.8 h) vs. urine
(Tmax 7.1 h). Urine BTM concentration (ng/mL) and amount (AUClast ; h * ng/mL)
were greater than plasma. HYD was suppressed for at least 3 days (<1 ng/mL) for
all horses. The time of last quantifiable concentration of BTM (Tlast ; hour) was
not significantly different in plasma than urine. Use of highly sensitive HPLC
MS/MS assays enabled early detection and prolonged and consistent determination
of BTM in plasma and urine.
PMID- 25847082
TI - Effect of persistent and transient hypothyroidism on histoarchitecture and
antioxidant defence system in rat brain.
AB - The present study reports the effect of 6-n-propylthiouracil (PTU)-induced
hypothyroidism on oxidative stress parameter, lipid peroxidation (LPx) and major
antioxidant enzyme expressions such as superoxide dismutase (SOD: SOD1 and SOD2)
and catalase (CAT) in cerebral cortex rat brain during postnatal persistent (90
days PTU treatment from birth) and transient (30 days PTU treatment from birth
followed by PTU withdrawal for 60 days) hypothyroidism. Enhanced level of LPx was
observed in transient hypothyroid rats with respect to control and persistent
hypothyroid rats. Significantly increased activity of SOD and expression of SOD1
were observed in cerebral cortex of both persistent and transient hypothyroid
rats as compared to control. However, unaltered translated level of SOD2 was
observed among the groups. Activity of CAT was increased in transient hypothyroid
rats, whereas translate level of CAT was increased in both the regions of
persistent as well as transient hypothyroidism. The histoarchitecture of cerebral
cortex clearly showed a decline in neuronal migration with neurons packed
together in both persistent and transient hypothyroid rats as compared to
control. These results suggest that deprivation of thyroid hormone modulates
redox status and causes oxidative stress in rat brain cerebral cortex during
postnatal development and maturation.
PMID- 25847083
TI - STIMA: a short screening test for ideo-motor apraxia, selective for action
meaning and bodily district.
AB - We propose STIMA, a short test for ideo-motor apraxia, allowing us to quantify
the apraxic deficit according to action meaning and affected body segment. STIMA
is based on a neurocognitive model holding that there are two processes involved
in action imitation (i.e., a semantic route for recognizing and imitating known
gestures, and a direct route for reproducing new gestures). The test allows to
identify which imitative process has been selectively impaired by brain damage
(direct vs. semantic route) and possible deficits depending on the body segment
involved (hand/limb vs. hand/fingers). N = 111 healthy participants were
administered with an imitation task in two separated blocks of known and new
gestures. In each block, half of the gestures were performed mainly with the
proximal part of the upper limb and the remaining half with the distal one. It
resulted in 18 known gestures (nine proximal and nine distal) and 18 new gestures
(nine proximal and nine distal) for a total of 36. Each gesture was presented up
to a maximum of two times. Detailed criteria are used to assign the final
imitation score. Cut offs, equivalent scores and main percentile scores were
computed for each subscale. Participants imitated better known than new gestures,
and proximal better than distal gestures. Age influenced performance on all
subscales, while education only affected one subscale. STIMA is easy and quick to
administer, and compared to previous tests, it offers important information for
planning adequate rehabilitation programs based on the functional locus of the
deficit.
PMID- 25847084
TI - Gender-specific effects of CGP 55845, GABAB receptor antagonist, on neuromuscular
coordination, learning and memory formation in albino mouse following neonatal
hypoxia-ischemia insult.
AB - GABAB receptor antagonists are experimentally proved as spatial memory enhancers
in mouse models but their role has not been described following hypoxic-ischemic
insult. 10-day-old albino mice were subjected to Murine model of hypoxia and
ischemia. Following brain damage, mice were fed on normal rodent diet till they
were 13 weeks old. At this time point, mice were divided into two groups. Group 1
received saline and group 2 received intraperitoneally CGP 55845 (1 mg/ml
solvent/Kg body weight) for 12 days. Behavioural observations were made during
rota rod, open field and Morris water maze test along with brain infarct
measurement in both CGP 55845 treated and untreated groups. It was observed that
application of GABAB receptor antagonist improved the over all motor function in
male and female albino mice but effects were more pronounced in males. In open
field, CGP 55845-treated female mice showed poor performance. CGP 55845 had no
significant effect on learning and memory formation during Morris water maze test
and also on brain infract size in both genders following hypoxia ischemia
encephalopathy. Effects of CGP 55845 can be further explored in a dose and
duration dependent manner to improve the learning and memory in albino mice
following neonatal brain damage.
PMID- 25847085
TI - An epidemiologic study of restless legs syndrome among Chinese children and
adolescents.
AB - To determine the prevalence of restless legs syndrome (RLS) in Chinese children
and adolescents as well as the impact of the disorder on 8-11 and 12-17 years
old. This population-based study was conducted in five primary schools and seven
high schools, which were randomly selected in Henan province, China. A total of
6792 students aged 8-17 years old were given a questionnaire that included the
adult diagnostic criteria of RLS proposed by the International Restless Legs
Study Group. Subjects who answered "yes" to all four questions were selected for
a face-to-face interview to confirm RLS diagnosis. Individuals with definite RLS
were then administered another questionnaire to survey RLS symptoms and perceived
consequences. The prevalence of definite RLS in Chinese children and adolescents
was 2.2 % (141/6437), with a prevalence of 1.8 % in the 8-11 years old age group
and 2.4 % in the 12-17 years old age group. RLS was found to be more prevalent in
females (2.7 %) than in males (1.7 %) (P = 0.008), and the prevalence of RLS was
determined to increase with age. Sleep disturbance was the most common symptom of
RLS in children and adolescents. Various consequences were attributed to RLS,
with participants reporting that they dreaded the arrival of evening/night most
frequently, followed by the description that RLS had a negative impact on mood.
These data suggest that RLS is prevalent in Chinese children and adolescents, and
that those affected by this disorder suffer from disruptions to sleep and daytime
function.
PMID- 25847087
TI - Prognosis of implant longevity in terms of annual bone loss: a methodological
finite element study.
AB - Dental implant failure is mainly the consequence of bone loss at peri-implant
area. It usually begins in crestal bone. Due to this gradual loss, implants
cannot withstand functional force without bone overload, which promotes
complementary loss. As a result, implant lifetime is significantly decreased. To
estimate implant success prognosis, taking into account 0.2 mm annual bone loss
for successful implantation, ultimate occlusal forces for the range of commercial
cylindrical implants were determined and changes of the force value for each
implant due to gradual bone loss were studied. For this purpose, finite element
method was applied and von Mises stresses in implant-bone interface under 118.2 N
functional occlusal load were calculated. Geometrical models of mandible segment,
which corresponded to Type II bone (Lekholm & Zarb classification), were
generated from computed tomography images. The models were analyzed both for
completely and partially osseointegrated implants (bone loss simulation). The
ultimate value of occlusal load, which generated 100 MPa von Mises stresses in
the critical point of adjacent bone, was calculated for each implant. To estimate
longevity of implants, ultimate occlusal loads were correlated with an
experimentally measured 275 N occlusal load (Mericske-Stern & Zarb). These
findings generally provide prediction of dental implants success.
PMID- 25847086
TI - Ecological host fitting of Trypanosoma cruzi TcI in Bolivia: mosaic population
structure, hybridization and a role for humans in Andean parasite dispersal.
AB - An improved understanding of how a parasite species exploits its genetic
repertoire to colonize novel hosts and environmental niches is crucial to
establish the epidemiological risk associated with emergent pathogenic genotypes.
Trypanosoma cruzi, a genetically heterogeneous, multi-host zoonosis, provides an
ideal system to examine the sylvatic diversification of parasitic protozoa. In
Bolivia, T. cruzi I, the oldest and most widespread genetic lineage, is pervasive
across a range of ecological clines. High-resolution nuclear (26 loci) and
mitochondrial (10 loci) genotyping of 199 contemporaneous sylvatic TcI clones was
undertaken to provide insights into the biogeographical basis of T. cruzi
evolution. Three distinct sylvatic parasite transmission cycles were identified:
one highland population among terrestrial rodent and triatomine species, composed
of genetically homogenous strains (Ar = 2.95; PA/L = 0.61; DAS = 0.151), and two
highly diverse, parasite assemblages circulating among predominantly arboreal
mammals and vectors in the lowlands (Ar = 3.40 and 3.93; PA/L = 1.12 and 0.60;
DAS = 0.425 and 0.311, respectively). Very limited gene flow between neighbouring
terrestrial highland and arboreal lowland areas (distance ~220 km; FST = 0.42 and
0.35) but strong connectivity between ecologically similar but geographically
disparate terrestrial highland ecotopes (distance >465 km; FST = 0.016-0.084)
strongly supports ecological host fitting as the predominant mechanism of
parasite diversification. Dissimilar heterozygosity estimates (excess in
highlands, deficit in lowlands) and mitochondrial introgression among lowland
strains may indicate fundamental differences in mating strategies between
populations. Finally, accelerated parasite dissemination between densely
populated, highland areas, compared to uninhabited lowland foci, likely reflects
passive, long-range anthroponotic dispersal. The impact of humans on the risk of
epizootic Chagas disease transmission in Bolivia is discussed.
PMID- 25847088
TI - Brain metabolism in minimal hepatic encephalopathy assessed by 3.0-Tesla magnetic
resonance spectroscopy.
AB - AIM: To examine whether the brain exhibits metabolic disorder prior to overt
hepatic encephalopathy in patients with liver cirrhosis (LC), the intracerebral
glutamine and myo-inositol levels were determined using 3.0-Tesla (T)(1) H
(proton) magnetic resonance spectroscopy (MRS). METHODS: We tested 21 LC
patients, including seven patients with minimal hepatic encephalopathy (MHE).
RESULTS: No significant differences were noted between the two patient groups in
terms of the severity of LC, levels of blood ammonia or levels of blood or liver
enzymes. In the MHE group, the levels of brain glutamine were significantly
higher than those in the non-MHE group, whereas the levels of brain myo-inositol
were significantly lower. This demonstrated that MHE patients were already
exhibiting metabolic disorder in the brain, similar to those observed during
overt hepatic encephalopathy. CONCLUSION: A quantitative analysis of this
phenomenon using MRS may contribute to an early and objective diagnosis of MHE.
PMID- 25847089
TI - Impact of n-3 polyunsaturated fatty acids in predicting ischemia/reperfusion
injury and progression of myocardial damage after reperfusion in patients with ST
segment elevation acute myocardial infarction.
AB - BACKGROUND: In animal models of acute myocardial infarction, n-3 polyunsaturated
fatty acids (PUFAs) administered before coronary occlusion have been suggested to
prevent induction of ventricular arrhythmia and limit infarct size. However, the
relation between the serum levels of n-3 PUFAs and ischemia/reperfusion (I/R)
injury remains unclear. METHODS: 211 patients with ST-segment elevation acute
myocardial infarction received emergency percutaneous coronary intervention (PCI)
within 6h from the onset. The patients were divided into two groups according to
the sum of serum eicosapentaenoic acid (EPA) levels and docosahexaenoic acid
(DHA) levels before PCI: group L (n=106), EPA+DHA <155MUg/ml and group H (n=105),
EPA+DHA >=155MUg/ml. The Selvester QRS-scoring system was used to estimate the
serial change in infarct size. RESULTS: Time to reperfusion was similar between
the 2 groups. The QRS score before PCI was higher in group L than in group H
(2.42+/-2.00 vs 1.85+/-2.01, p=0.015). The proportion of patients with I/R injury
immediately after reperfusion, defined as reperfusion ventricular arrhythmias
(25% vs 11%, p=0.006) and ST-segment re-elevation (44% vs 22%, p<0.001), was also
higher in group L than in group H, followed by a greater increment in the QRS
score during PCI (3.51+/-2.51 vs 2.54+/-1.91, p=0.006) and higher peak levels of
creatinine phosphokinase (3552+/-241U/L vs 2660+/-242U/L, p<0.01). On
multivariate analysis, serum level of EPA+DHA was an independent predictor of
reperfusion injury (odds ratio 0.985, p=0.032). CONCLUSION: Serum level of n-3
PUFAs before PCI may be a predictor of I/R injury and the resultant extent of
myocardial damage. These findings suggest a protective effect of serum n-3 PUFAs
on ischemic myocardium.
PMID- 25847090
TI - Clinical and angiographic outcomes of paclitaxel-eluting coronary stent
implantation in hemodialysis patients: A prospective multicenter registry: The
OUCH-TL study (outcome in hemodialysis of TAXUS Liberte).
AB - BACKGROUND: The outcome of percutaneous coronary intervention (PCI) has been
reported to be poor in hemodialysis (HD) patients even in the drug-eluting stent
era. We have reported relatively poor outcomes after sirolimus-eluting stent
implantation in the OUCH study. METHODS: The OUCH-TL study is a prospective, non
randomized, single-arm registry designed to assess the results of paclitaxel
eluting stent (PES) in HD patients with follow-up quantitative coronary
angiography analysis. The primary endpoint was the occurrence of target-vessel
failure (TVF) defined as cardiac death, myocardial infarction (MI), and target
vessel revascularization (TVR) at 12 months. RESULTS: A total of 119 patients
with 154 lesions were enrolled (one withdrawal). Mean age was 65+/-10 years, male
gender was 79%, 89% of cases had stable coronary disease. Diabetic nephropathy
was diagnosed in 61% of the patients. American College of Cardiology/American
Heart Association type B2/C accounted for 96% of lesions and 22.7% of lesions
were treated with Rotablator (Boston Scientific Corporation, Natick, MA, USA).
Rates of TVF, death, MI, stent thrombosis and TVR at 12 months were 20.2%, 5.9%,
5.0%, 1.4%, and 12.6%, respectively. TVR was performed in 8.4% of the patients up
to 12 months. Late loss in-stent was 0.48+/-0.61mm, and late loss in-segment was
0.37+/-0.61mm at 9 months. Binary restenosis in-stent was 10.3% and in-segment
was 14.5%. CONCLUSIONS: Outcomes of PES implantation in hemodialysis patients
appears comparable to those of non-hemodialysis patients.
PMID- 25847091
TI - Pre-procedural evaluation of the left atrial anatomy in patients referred for
catheter ablation of atrial fibrillation.
AB - BACKGROUND: Cardiac computed tomography (CT) provides accurate imaging of the
pulmonary vein (PV) and left atrial (LA) anatomy. This study aimed to evaluate
the prevalence and morphological characteristics of anatomical variants that
could influence atrial fibrillation (AF) ablation procedures. METHODS AND
RESULTS: One thousand forty consecutive patients (62+/-10 years, 243 female, 644
paroxysmal AF) undergoing pre-procedural imaging with a 320-row CT and their
first AF ablation procedure were analyzed. A total of 194 (18.7%) patients had
anatomical variants. Left, right, and inferior common PVs were observed in 118,
5, and 6 patients, respectively. Three right and left PVs were observed in 44 and
4 patients, respectively. Three patients had remnants of PVs after lobectomies,
and significant PV stenosis was observed in one. Supernumerary PVs that drained
into the LA and diverticula were observed in eight patients. One patient had a
string-like structure connecting the LA septum and posterior LA, and the others
had membranous structures incompletely compartmentalizing the LA. Three patients
had persistent left superior vena cavae, two strong deviations of the LA and PVs,
and one dexiocardia. All patients underwent successful PV isolation during the
index procedure. CONCLUSIONS: Patients referred for AF ablation often have
anatomical variants, which could influence the procedure. This information might
aid in planning procedural strategies, and reducing unexpected procedural
complications in AF ablation.
PMID- 25847092
TI - Quantifying space use of breeders and floaters of a long-lived species using
individual movement data.
AB - To date, animal movement studies have mostly analysed the movement behaviours of
individuals at specific times of their lives, but we lack detailed information on
how individual movements may be affected by the various and different changes
that individuals experience throughout their life (e.g. life history phases,
experience, age). Here, we attempt to identify differences in home range and
movement behaviour between two different statuses, disperser vs. breeder, of a
long-lived species (the eagle owl Bubo bubo). Information on home range and
movement behaviour between different stages of an individual life are crucial for
species conservation and management, as well as for basic knowledge on space use
and rhythm of activity. Does the transition from an exploratory stage to moving
within more familiar surroundings call for changes in the movement behaviour? We
observed notable differences during the two stages of the owls' lives, with
individuals having different home range behaviours and rhythms of activity
depending on their social status. Significant differences in home range behaviour
between the sexes began only with the acquisition of a breeding site. Breeders
showed larger home ranges than dispersing individuals, although nightly variation
of home ranges size was higher for dispersers than for breeders. Finally,
dispersers were active throughout the night, whereas breeders displayed a less
active movement phase at both the beginning and end of the night. Our results
demonstrate it is important to consider individual variations in space use and
movement behaviour due to the different life history phases that they attain
during their lifetime. The knowledge of the different needs of a species across
life stages may represent an important tool for species conservation because each
phase of an individual life may need different requirements.
PMID- 25847093
TI - Massed and distributed repetition of natural scenes: Brain potentials and
oscillatory activity.
AB - Neural measures of repetition can result in either repetition suppression or
enhancement effects, with enhancement sometimes interpreted as indicating
episodic retrieval, rather than stimulus habituation. Here, we manipulated
whether repetitions were massed (consecutive) or distributed (intermixed) and
measured event-related potentials and oscillatory activity, investigating the
question of whether there is evidence of "spontaneous" episodic retrieval for
distributed, but not massed, repetition. Results showed that distributed
repetition uniquely prompted a significant centroparietal old-new effect as well
as enhanced theta, compared to either novel presentations or massed repetitions,
consistent with a hypothesis of spontaneous retrieval. Massed repetition, on the
other hand, prompted repetition suppression and reduction of the N2/P2. Taken
together, the data suggest that distributed repetition may facilitate later
memory performance because it spontaneously retrieves prior representations.
PMID- 25847094
TI - Testing for polygenic effects in genome-wide association studies.
AB - To confirm associations with a large number of single nucleotide polymorphisms
(SNPs), each with only a small effect size, as hypothesized in the polygenic
theory for schizophrenia, the International Schizophrenia Consortium (2009,
Nature 460:748-752) proposed a polygenic risk score (PRS) test and demonstrated
its effectiveness when applied to psychiatric disorders. The basic idea of the
PRS test is to use a half of the sample to select and up-weight those more likely
to be associated SNPs, and then use the other half of the sample to test for
aggregated effects of the selected SNPs. Intrigued by the novelty and increasing
use of the PRS test, we aimed to evaluate and improve its performance for GWAS
data. First, by an analysis of the PRS test, we point out its connection with the
Sum test [Chapman and Whittaker, Genet Epidemiol 32:560-566; Pan, Genet Epidemiol
33:497-507]; given the known advantages and disadvantages of the Sum test, this
connection motivated the development of several other polygenic tests, some of
which may be more powerful than the PRS test under certain situations. Second,
more importantly, to overcome the low statistical efficiency of the data
splitting strategy as adopted in the PRS test, we reformulate and thus modify the
PRS test, obtaining several adaptive tests, which are closely related to the
adaptive sum of powered score (SPU) test studied in the context of rare variant
analysis [Pan et al., 2014, Genetics 197:1081-1095]. We use both simulated data
and a real GWAS dataset of alcohol dependence to show dramatically improved power
of the new tests over the PRS test; due to its superior performance and
simplicity, we recommend the whole sample-based adaptive SPU test for polygenic
testing. We hope to raise the awareness of the limitations of the PRS test and
potential power gain of the adaptive SPU test.
PMID- 25847095
TI - Old sleeping Sicilian beauty: seed germination in the palaeoendemic Petagnaea
gussonei (Spreng.) Rauschert (Saniculoideae, Apiaceae).
AB - Petagnaea gussonei (Apiaceae) is a perennial herbaceous species endemic to
northeast Sicily (Nebrodi Mountains). It is considered a remnant of the Sicilian
Tertiary flora, and is endangered according to the Red List. There is no
information in the literature about the germinability of its seeds, even though
seed production is know to occur. The aim of this study was to obtain data to
better understand seed germination of this species and its biological
implications. Thus, several approaches were employed: vitality analyses,
gibberellic acid supply, germination and soil microbial flora analyses via end
point and qPCR. The results suggest that seed germination occurs after ca. 1.5
years at a rate of ca. 11%. The seeds can be classified as physiologically
dormant, and probably require prolonged cold stratification for germination.
Because seed germination is low, it is likely that agamic reproduction represents
an important mean for its conservation and survival. These results have important
implications for P. gussonei survival and should be considered in possible re
introduction attempts aimed at restoring threatened populations.
PMID- 25847096
TI - Links between genome replication and chromatin landscapes.
AB - Post-embryonic organogenesis in plants requires the continuous production of
cells in the organ primordia, their expansion and a coordinated exit to
differentiation. Genome replication is one of the most important processes that
occur during the cell cycle, as the maintenance of genomic integrity is of
primary relevance for development. As it is chromatin that must be duplicated, a
strict coordination occurs between DNA replication, the deposition of new
histones, and the introduction of histone modifications and variants. In turn,
the chromatin landscape affects several stages during genome replication. Thus,
chromatin accessibility is crucial for the initial stages and to specify the
location of DNA replication origins with different chromatin signatures. The
chromatin landscape also determines the timing of activation during the S phase.
Genome replication must occur fully, but only once during each cell cycle. The re
replication avoidance mechanisms rely primarily on restricting the availability
of certain replication factors; however, the presence of specific histone
modifications are also revealed as contributing to the mechanisms that avoid re
replication, in particular for heterochromatin replication. We provide here an
update of genome replication mostly focused on data from Arabidopsis, and the
advances that genomic approaches are likely to provide in the coming years. The
data available, both in plants and animals, point to the relevance of the
chromatin landscape in genome replication, and require a critical evaluation of
the existing views about the nature of replication origins, the mechanisms of
origin specification and the relevance of epigenetic modifications for genome
replication.
PMID- 25847097
TI - Complex alterations in microglial M1/M2 markers during the development of
epilepsy in two mouse models.
AB - OBJECTIVE: To characterize the changes in microglial proinflammatory M1 and
antiinflammatory M2 marker expression during epileptogenesis in the chronic
pilocarpine and intrahippocampal kainate models. METHODS: M1-activated microglia
express proinflammatory cytokines driving infiltration of cells, whereas M2
activated microglia are more reparative, promoting phagocytosis of debris and
expression of proteins associated with cellular stability and repair. Microglial
markers were characterized as acute (3 days after status epilepticus [SE]), early
chronic (21 days post-SE), and late chronic epileptic (5-12 months post-SE) time
points. Following pilocarpine-SE, microglial markers were assessed by flow
cytometry. Quantitative real-time polymerase chain reaction (RT-PCR) was used to
measure messenger RNA (mRNA) levels of selected M1 (interleukin [IL] 1beta, tumor
necrosis factor alpha [TNFalpha] cluster of differentiation [CD],CD16, and CD86),
interleukin-6 [IL-6], interleukin-12 [IL-12], Fc receptors 16, and CD86) and M2
(arginase 1 [Arg1], chitinase-3-like protein [Ym1], found in inflammatory zone
[FIZZ-1] [FIZZ-1], mannose receptor C type-1 [CD206], interleukin-4 [IL-4], and
interleukin-10 (IL-10)) markers in both models. Video-electroencephalography
(EEG) recordings were used to quantify late chronic seizure frequency. RESULTS:
Three days post-SE microglia in the pilocarpine model expressed M1 and M2
markers, but only M1 markers were upregulated after kainate-induced SE. After 3
weeks, M1/M2 marker expression was largely ablated in the hippocampal formation
of both models. Small mRNA level increases of CD11b, glial fibrillary acidic
protein (GFAP), and IL-1beta were found in the pilocarpine model, consistent with
IL-1beta contributing to spontaneous seizures, whereas mRNA levels of TNFalpha
and Ym1 were decreased. In the late chronic phase, some M1/M2 markers, IL-1beta,
TNFalpha, Arg1, Ym1, and CD206, resurged in the kainate, but not pilocarpine
model, which may reflect and/or contribute to highly frequent seizures in kainate
SE mice. SIGNIFICANCE: The common M1 upregulation acutely post-SE may signal a
role early in epileptogenesis, with a more pure "inflamed" central nervous system
state after kainate-SE, potentially contributing to the development of more
frequent seizures. The difference may also be due to the contribution of
peripheral inflammation after pilocarpine injection. In summary, the microglial
inflammatory response during epileptogenesis is complex, varies between models,
and appears to correlate with chronic seizure frequency.
PMID- 25847098
TI - Adverse Perinatal Outcomes among Immigrant Women from Ethiopia in Israel.
AB - BACKGROUND: Immigration from Ethiopia to Israel started about 30 years ago. We
aimed to compare birth outcomes between Israeli women of Ethiopian origin and
Israeli-born, non-Ethiopian women. We hypothesized a higher frequency of adverse
birth outcomes among Ethiopian women and a trend of improvement among those who
were raised in Israel since early childhood. METHODS: This is a descriptive
study, comparing birth outcomes of Ethiopian (n = 1,319) and non-Ethiopian women
(n = 27,307) who gave birth in a medical center in Central Israel in 2002 to
2009. Ethiopian women were further categorized by age at immigration. Logistic
regressions were constructed to compare the incidence of adverse birth outcomes
between Ethiopian and non-Ethiopian women, controlling for potential confounders.
RESULTS: Ethiopian women had about twice the incidence of very and extremely
preterm births, compared with non-Ethiopians. Ethiopian women had twice the odds
for neonates who were either small for gestational age or had low 5-minute Apgar
scores. Ethiopian women had about threefold increased risk of stillbirths (OR 2.9
[95% CI 1.87-4.49]). No trend of improvement was noted for women who were raised
in Israel from early childhood. CONCLUSION: Ethiopian women are at increased risk
of adverse birth outcomes. Future research is needed to investigate the
underlying causes for the increased risks and lack of improvement among those who
were raised in Israel that will lead to effective interventions.
PMID- 25847099
TI - Distinct clinical and radiographic characteristics of moyamoya disease amongst
European Caucasians.
AB - BACKGROUND AND PURPOSE: Occlusive cerebrovascular moyamoya disease (MMD) is rare
and has been characterized mainly in Asian countries, so far. In recent years,
MMD has been increasingly reported worldwide, raising the question whether its
clinical presentation would vary amongst different ethnic backgrounds. Here, a
homogeneous series of 153 patients with MMD are reported and the specific
clinical features of this rare disease amongst European Caucasians are
highlighted. METHODS: A total of 153 European Caucasians with MMD who were
treated in our institution between 1997 and 2014 were retrospectively identified.
Demographic data, clinical symptoms, angiographic characteristics and functional
hemodynamic studies were analyzed. RESULTS: Moyamoya disease presented with a
female predominance of 2,9:1.,78% presented with a typical MMD, 17% with a
unilateral MMD and 5% with an atypical MMD. 16% of our patients belonged to the
pediatric population. Overall, 81% and 8.5% of our cohort presented initially
with ischaemic and hemorrhagic manifestation, respectively. The rate of
hemorrhagic manifestation of MMD amongst the pediatric group was slightly higher
(12%). Angiographic analysis revealed steno-occlusive involvement of the
posterior circulation in 34% with a higher involvement in pediatric patients
(64%) compared to adults (28%). CONCLUSIONS: The characterization of our
homogeneous European Caucasian cohort reveals several significant differences
compared to Asian cohorts. In contrast, MMD presents similarly amongst European
and North American cohorts, suggesting that non-Asian MMD is characterized by
distinct clinical features.
PMID- 25847100
TI - Towards solar energy storage in the photochromic dihydroazulene-vinylheptafulvene
system.
AB - One key challenge in the field of exploitation of solar energy is to store the
energy and make it available on demand. One possibility is to use photochromic
molecules that undergo light-induced isomerization to metastable isomers. Here we
present efforts to develop solar thermal energy storage systems based on the
dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch. New DHA
derivatives with one electron-withdrawing cyano group at position 1 and one or
two phenyl substituents in the five-membered ring were prepared by using
different synthetic routes. In particular, a diastereoselective reductive removal
of one cyano group from DHAs incorporating two cyano groups at position 1 turned
out to be most effective. Quantum chemical calculations reveal that the
structural modifications provide two benefits relative to DHAs with two cyano
groups at position 1: 1) The DHA-VHF energy difference is increased (i.e., higher
energy capacity of metastable VHF isomer); 2) the Gibbs free energy of activation
is increased for the energy-releasing VHF to DHA back-reaction. In fact,
experimentally, these new derivatives were so reluctant to undergo the back
reaction at room temperature that they practically behaved as DHA to VHF one-way
switches. Although lifetimes of years are at first attractive, which offers the
ultimate control of energy release, for a real device it must of course be
possible to trigger the back-reaction, which calls for further iterations in the
future.
PMID- 25847101
TI - Modulation of pumping rate by two species of marine bivalve molluscs in response
to neurotransmitters: Comparison of in vitro and in vivo results.
AB - Most studies regarding the neuroanatomy and neurophysiology of molluscan ctenidia
have focused on isolated ctenidial tissue preparations. This study investigated
how bivalve molluscs modulate their feeding rates by examining the effects of a
variety of neurotransmitters, including serotonin, dopamine, and the dopamine
agonist apomorphine on both isolated ctenidial tissue and in intact members of
two commercially important bivalve species: the blue mussel, Mytilus edulis; and
the bay scallop Argopecten irradians. In particular, we examined the effect of
changes in: 1) beat of the lateral cilia (in vitro), 2) distance between
ctenidial filaments and/or plicae (in vivo), and 3) diameter of the siphonal
openings (in vivo) on alteration of bulk water flow through the mantle cavity.
Important differences were found between isolated tissue and whole animals, and
between species. Drugs that stimulated ciliary beat in vitro did not increase
water processing rate in vivo. None of the treatments increased water flow
through the mantle cavity of intact animals. Results suggest that A. irradians
was primarily modulating lateral ciliary activity, while M. edulis appeared to
have a number of ways to control water processing activity, signifying that the
two species may have different compensatory and regulatory mechanisms controlling
feeding activity.
PMID- 25847102
TI - The distance between breast cancer and the skin is associated with axillary nodal
metastasis.
AB - BACKGROUND AND OBJECTIVES: More superficially located tumors may be more likely
than deeper tumors to metastasize to the axillary nodes via the lymphatics. The
aim of this study was to determine whether breast cancer distance from the skin
affects axillary node metastasis, ipsilateral breast cancer recurrence, or
recurrence-free survival. MATERIALS AND METHODS: A total of 1,005 consecutive
patients with breast cancer who underwent surgery between January 2003 and
December 2009 were selected. The distance of the tumor from the skin was measured
from the skin to the most anterior hypoechoic leading edge of the lesion.
RESULTS: In total, 603 (68%) patients had no axillary nodal metastasis, and 288
(32%) had axillary nodal metastasis. A breast cancer distance from the skin <3 mm
induced more axillary nodal metastasis (P = 0.039). However, no significant
correlation was observed between breast cancer distance from the skin <3 mm and
ipsilateral breast cancer recurrence (P = 0.788) or recurrence-free survival (P =
0.353). CONCLUSIONS: Breast cancers located closer to the skin had a higher
incidence of axillary nodal metastasis. Therefore, tumor distance from the skin
should be considered when evaluating a patient with breast cancer and considering
the risk of nodal metastasis.
PMID- 25847103
TI - The occurrence and ecological risk assessment of phthalate esters (PAEs) in urban
aquatic environments of China.
AB - Phthalate esters (PAEs) are widely used in the manufacturing of plastics, and the
demand for PAEs has grown rapidly, especially in China. This trend will lead to
much more environmental PAE contamination. PAEs are listed as priority substances
in the European Union and are therefore subject to ecological risk assessments.
This paper reviews the literature concerning the pollution status of PAEs and
their ecological risk to aquatic environments. Risk quotients (RQs) based on the
predicted no effect concentration and PAE concentrations in aquatic environments
demonstrated significant (10 <= RQ < 100) or expected (RQ >= 100) potential
adverse effects for algae, Daphnia, and fish in aquatic environments near PAE
based industrial and urban areas. Thus, the ecological risk of PAEs in Chinese
aquatic environments should be considered, especially in areas where commercial
plastics are produced.
PMID- 25847104
TI - Assessment for water quality by artificial neural network in Daya Bay, South
China Sea.
AB - In this study, artificial neural network such as a self-organizing map (SOM) was
used to assess for the effects caused by climate change and human activities on
the water quality in Daya Bay, South China Sea. SOM has identified the
anthropogenic effects and seasonal characters of water quality. SOM grouped the
four seasons as four groups (winter, spring, summer and autumn). The Southeast
Asian monsoons, northeasterly from October to the next April and southwesterly
from May to September have also an important influence on the water quality in
Daya Bay. Spatial pattern is mainly related to anthropogenic activities and
hydrodynamics conditions. In spatial characteristics, the water quality in Daya
Bay was divided into two groups by chemometrics. The monitoring stations (S3, S8,
S10 and S11) were in these area (Dapeng Ao, Aotou Harbor) and northeast parts of
Daya Bay, which are areas of human activity. The thermal pollution has been
observed near water body in Daya Bay Nuclear Power Plant (S5). The rest of the
monitoring sites were in the south, central and eastern parts of Daya Bay, which
are areas that experience water exchanges from South China Sea. The results of
this study may provide information on the spatial and temporal patterns in Daya
Bay. Further research will be carry out more research concerning functional
changes in the bay ecology with respect to changes in climatic factor, human
activities and bay morphology in Daya Bay.
PMID- 25847105
TI - Ecotoxicological evaluation of propranolol hydrochloride and losartan potassium
to Lemna minor L. (1753) individually and in binary mixtures.
AB - Antihypertensive pharmaceuticals, including the beta-blockers, are one of the
most detected therapeutic classes in the environment. The ecotoxicity of
propranolol hydrochloride and losartan potassium was evaluated, both individually
and combined in a binary mixture, by using the Lemna minor growth inhibition
test. The endpoints evaluated in the single-pharmaceutical tests were frond
number, total frond area and fresh weight. For the evaluation of the mixture
toxicity, the selected endpoint was frond number. Water quality criteria values
(WQC) were derived for the protection of freshwater and saltwater pelagic
communities regarding the effects induced by propranolol and losartan using
ecotoxicological data from the literature, including our data. The risks
associated with both pharmaceutical effects on non-target organisms were
quantified through the measured environmental concentration (MEC)/predicted-no
effect concentration (PNEC) ratios. For propranolol, the total frond area was the
most sensitive endpoint (EC50 = 77.3 mg L(-1)), while for losartan there was no
statistically significant difference between the endpoints. Losartan is only
slightly more toxic than propranolol. Both concentration addition and independent
action models overestimated the mixture toxicity of the pharmaceuticals at all
the effect concentration levels evaluated. The joint action of both
pharmaceuticals showed an antagonistic interaction to L. minor. Derived WQC
assumed lower values for propranolol than for losartan. The MEC/PNEC ratios
showed that propranolol may pose a risk for the most sensitive aquatic species,
while acceptable risks posed by losartan were estimated for most of aquatic
matrices. To the authors knowledge these are the first data about losartan
toxicity for L. minor.
PMID- 25847106
TI - Acaricide-impaired functional predation response of the phytoseiid mite
Neoseiulus baraki to the coconut mite Aceria guerreronis.
AB - Acaricides may interfere with a myriad of interactions among arthropods,
particularly predator-prey interactions. The coconut mite, Aceria guerreronis
Keifer (Acari: Eriophyidae), and its phytoseiid predator, Neoseiulus baraki
(Athias-Henriot) (Acari: Phytoseiidae), provide an opportunity to explore such
interference because the former is a key coconut pest species that requires both
predation and acaricide application for its management. The objective of the
present study was to assess the effect of the acaricides abamectin, azadirachtin
and fenpyroximate on the functional response of N. baraki to A. guerreronis
densities. The following prey densities were tested: 5, 10, 20, 40 and 80 preys.
The type of functional response and prey handling time (Th) were not altered by
the acaricides. However, the attack rate (a') was modified by abamectin and
fenpyroximate, and the consumption peak was reduced by abamectin. All of the
acaricides allowed for the maintenance of the predator in the field, but exposure
to abamectin and fenpyroximate compromised prey consumption.
PMID- 25847107
TI - Revitalizing traditional ecological knowledge: a study in an Alpine rural
community.
AB - This study aims to contribute to the debate on the value and the role of
ecological knowledge in modern conservation strategies, with reference to the
results of a case study conducted in the community of Montagne, located within a
World Heritage site in the Italian Alps. This community is a paradigmatic example
of the multiple transformations experienced by cultural landscapes in Alpine
areas under the influence of global change. This study seeks to understand
whether ecological knowledge is still in place in the community, and what the
relationship is between the knowledge transmission and land use and social
changes that have occurred in recent decades. To that end, the community is
described by identifying the key variables (social, institutional, and
ecological) that have historically shaped the landscape and the future priorities
of the residents. Forest expansion, the most significant change in land use in
the last 60 years, is analyzed using aerial photos; changes in biodiversity
related knowledge in the community are quantified by analyzing the inter
generational differences in plant species recognition. Results are discussed in
the context of the current situation of the Montagne community, and the
recommendation is made that policies and actions to promote traditional
ecological knowledge protection or recovery in Europe be viewed as an important
part of the recovery of community sovereignty and vitality. Lastly, concrete
actions that can be implemented in our case study are proposed.
PMID- 25847108
TI - The Cultural Dimensions of Freshwater Wetland Assessments: Lessons Learned from
the Application of US Rapid Assessment Methods in France.
AB - Given the recent strengthening of wetland restoration and protection policies in
France, there is need to develop rapid assessment methods that provide a cost
effective way to assess losses and gains of wetland functions. Such methods have
been developed in the US and we tested six of them on a selection of contrasting
wetlands in the Isere watershed. We found that while the methods could
discriminate sites, they did not always give consistent rankings, thereby
revealing the different assumptions they explicitly or implicitly incorporate.
The US assessment methods commonly use notions of "old-growth" or "pristine" to
define the benchmark conditions against which to assess wetlands. Any reference
based assessment developed in the US would need adaptation to work in the French
context. This could be quite straightforward for the evaluation of hydrologic
variables as scoring appears to be consistent with the best professional judgment
of hydrologic condition made by a panel of French local experts. Approaches to
rating vegetation condition and landscape context, however, would require
substantial reworking to reflect a novel view of reference standard. Reference
standard in the European context must include acknowledgement that many of the
best condition and biologically important wetland types in France are the product
of intensive, centuries-long management (mowing, grazing, etc.). They must also
explicitly incorporate the recent trend in ecological assessment to focus
particularly on the wetland's role in landscape-level connectivity. These context
specific, socio-cultural dimensions must be acknowledged and adjusted for when
adapting or developing wetland assessment methods in new cultural contexts.
PMID- 25847109
TI - Tibial nerve F-wave recordings.
AB - INTRODUCTION: Tibial F-wave recordings are remarkable for their complexity and
persistence. We postulate that the signal recorded by the E2 (reference)
electrode causes this pattern. METHODS: Tibial F-wave recordings were made from
the abductor hallucis (AH) muscle using the standard montage in 10 subjects.
Additional far-field simultaneous F-wave recordings were made from the AH, the
base of the large toe, and the base of the small toe with the E2 placed on the
contralateral foot. RESULTS: F-wave recordings made in the standard manner and
from the base of the large or small toes showed complex waveforms and similar
latencies. Recordings made from the AH-contralateral foot had simple waveforms in
most subjects; in 2 subjects the latencies were longer, and 1 showed reduced
persistence. CONCLUSIONS: The tibial F-waves are composed primarily of volume
conducted recordings of the tibial-innervated foot muscles from the E2 electrode.
PMID- 25847110
TI - Extracardiac anomalies in prenatally diagnosed heterotaxy syndrome.
AB - OBJECTIVE: To assess the incidence and impact of extracardiac anomalies on the
prognosis of fetuses with heterotaxy syndrome. METHODS: All fetuses diagnosed
with heterotaxy syndrome by three experienced examiners over a period of 14 years
(1999-2013) were reviewed retrospectively. RESULTS: In total, 165 fetuses with
heterotaxy syndrome were diagnosed in the study period. One hundred and fifty
(90.9%) had cardiac defects; extracardiac anomalies that did not involve the
spleen were present in 26/165 (15.8%) cases. Of the total study cohort,
termination of pregnancy was performed in 49 (29.7%) cases, intrauterine death
occurred in 11 (6.7%), postnatal death occurred in 38 (23.0%) and 67 (40.6%) were
alive at the latest follow-up, resulting in a total perinatal and pediatric
mortality of 59.4%. Among the 105 liveborn neonates, 15 (14.3%) had extracardiac
anomalies with significant impact on the postnatal course: one neonate died
following repair of an encephalocele, six had successful treatment for various
types of intestinal malrotation and/or atresia and one underwent hiatal hernia
repair; the remaining seven had biliary atresia, of which five died and the two
survivors are awaiting liver transplantation. The status of the spleen was
assessed in 93/105 liveborn children and was found to be abnormal in 84/93
(90.3%). There were three cases of lethal sepsis, all associated with asplenia.
Of the 38 postnatal deaths, 29 (76.3%) had a cardiac cause, seven (18.4%) had an
extracardiac cause and in two (5.2%) the reason was uncertain. CONCLUSIONS:
Although the leading causes of death in fetuses and children with heterotaxy
syndrome are cardiac, a small subset of fetuses have extracardiac anomalies with
significant impact on outcome. These anomalies often escape prenatal detection,
and therefore neonates at risk should be monitored for bowel obstruction, biliary
atresia and immune dysfunction in order to allow timely intervention through a
multidisciplinary approach. Copyright (c) 2015 ISUOG. Published by John Wiley &
Sons Ltd.
PMID- 25847111
TI - Anatomical versus non-anatomical resection for hepatocellular carcinoma.
AB - BACKGROUND: The optimal surgical resection method in patients with HCC to
minimize the risk of local recurrence has not yet been determined. The aim of
this study was to compare the prognosis following anatomical versus non
anatomical hepatic resection for hepatocellular carcinoma (HCC). METHODS:
Consecutive patients with HCC without macroscopic vascular invasion, treated by
curative resection between 1981 and 2012 at Osaka Medical Centre, were included
in this retrospective study. The outcomes of patients selected by propensity
score matching were compared. RESULTS: Some 1102 patients were included, 577 in
the anatomical and 525 in the non-anatomical resection group. By propensity score
matching, 329 patients were selected into each group. Demographic, preoperative
and tumour variables were similar between the propensity score-matched groups,
including tumour size, tumour multiplicity, alpha-fetoprotein level and 15-min
indocyanine green retention rate at 15 min. The incidence of microvascular
invasion was higher in the matched anatomical resection group (P = 0.048).
Stratified analysis of recurrence-free and overall survival rates revealed no
statistically significant differences between the two propensity score-matched
groups (P = 0.704 and P = 0.381 respectively). There was also no significant
difference in the early recurrence rate within 2 years after resection between
these groups (P = 0.726). Subset analysis of the early recurrence-free survival
rate in patients with and without microvascular invasion revealed no significant
differences between the groups (P = 0.312 and P = 0.479 respectively).
CONCLUSION: The resection method had no impact on the risk of HCC recurrence or
survival.
PMID- 25847112
TI - Can drug effects explain the recent temporal increase in atonic postpartum
haemorrhage?
AB - BACKGROUND: Rates of postpartum haemorrhage and atonic postpartum haemorrhage
have increased in several high-income countries. We carried out a study to
examine if drug use in pregnancy, or drug and other interactions, explained this
increase in postpartum haemorrhage. METHODS: The linked administrative and
hospital databases of the Quebec Pregnancy Cohort were used to define a cohort of
pregnant women in Quebec, Canada, from 1998 to 2009 (n = 138,704). Case-control
studies on any postpartum haemorrhage and atonic postpartum haemorrhage were
carried out within this population, with up to five controls randomly selected
for each case after matching on index date and hospital of delivery (incidence
density sampling). Conditional logistic regression was used to estimate the
effects of drug use on postpartum haemorrhage and atonic postpartum haemorrhage.
RESULTS: There was an unexpected non-linear, declining temporal pattern in
postpartum haemorrhage and atonic postpartum haemorrhage between 1998 and 2009.
Use of antidepressants (mainly selective serotonin reuptake inhibitors) was
associated with higher rates of postpartum haemorrhage [adjusted rate ratio (aRR)
1.48, 95% confidence interval (CI) 1.23, 1.77] and atonic postpartum haemorrhage
[aRR 1.40, 95% CI 1.13, 1.74]. Thrombocytopenia was also associated with higher
rates of postpartum haemorrhage [aRR 1.52, 95% CI 1.16, 2.00]. There were no
statistically significant drug interactions. Adjustment for maternal factors and
drug use had little effect on temporal trends in postpartum haemorrhage and
atonic postpartum haemorrhage. CONCLUSIONS: Although antidepressant use and
thrombocytopenia were associated with higher rates of atonic postpartum
haemorrhage, antidepressant and other drug use did not explain temporal trends in
postpartum haemorrhage.
PMID- 25847113
TI - A maternally inherited 16p13.11-p12.3 duplication concomitant with a de novo SOX5
deletion in a male patient with global developmental delay, disruptive and
obsessive behaviors and minor dysmorphic features.
AB - We detail here the clinical description and the family genetic study of a male
patient with global developmental delay, disruptive and obsessive behaviors and
minor dysmorphic features and a combination of two rare genetic variants: a
maternally inherited 16p13.11-p12.3 duplication and a de novo 12p12.1 deletion
affecting SOX5. The 16p13.11 microduplication has been implicated in several
neurodevelopmental and behavioral disorders and is characterized by variable
expressivity and incomplete penetrance. The causes of this variation in
phenotypic expression are not fully clear, representing a challenge in genetic
diagnosis and counseling. However, several authors have proposed the two-hit
model as one of the underlying mechanisms for this phenotypic heterogeneity. Our
data could also support this two-hit model in which the 16p13.11-p12.3
duplication might contribute to the phenotype, not only as a single event but
also in association with the SOX5 deletion. The SOX5 gene plays important roles
in various developmental processes and has been associated with several
neurodevelopmental disorders, mainly intellectual disability, developmental delay
and language and/or speech delay as well as with behavior problems and dysmorphic
features. However, many of the physical features and behavioral manifestations as
well as language deficiencies present in our patient are consistent with those
previously reported for SOX5 deletions. Patients carrying multiple genomic
variants, as the one presented here, illustrate the difficulty in analyzing
genotypes when the contribution of each variant results in overlapping phenotypes
and/or, alternatively, in the modification of the clinical manifestations defined
by the coexisting variant.
PMID- 25847116
TI - Renal Autotransplantation in Lynch Syndrome: A Viable Option in a Patient With
Contralateral Metachronous Ureteral Cancer.
AB - The success of human kidney allotransplantation was realized over six decades
ago. First described 50 years ago, renal autotransplantation has been utilized
sparingly as a salvage procedure for patients at risk of losing renal function,
either from a benign or malignant condition. While classically associated with
colorectal malignancies, Lynch syndrome also carries a small yet significant risk
for the development of ureteral carcinoma. For these patients who develop chronic
kidney disease, allotransplantation may not be an option due to the lifelong risk
of several malignancies. We report the first known case of renal
autotransplantation in a patient with metachronous ureteral cancer due to Lynch
syndrome.
PMID- 25847117
TI - Sensitive and rapid assessment of amyloid by oligothiophene fluorescence in
subcutaneous fat tissue.
AB - Systemic amyloidosis (SA) is often diagnosed late. Combining clinical and
biochemical biomarkers is necessary for raising suspicion of disease. Fine needle
aspiration (FNA) of subcutaneous fat enables SA detection by Congo red staining.
The luminescent conjugated probe heptameric formic thiophene acetic acid (h-FTAA)
is a sensitive alternative to Congo red-staining of tissue samples. Our objective
was to compare h-FTAA fluorescence with the Congo red stain for amyloid detection
in FNA-obtained fat tissue. Herein, we studied samples from 57 patients with
established SA (19 with AA, 20 with AL, and 18 with ATTR) and 17 age-matched
controls (34-75 years). Positivity for h-FTAA was graded according to a Congo red
based grading scale ranging from 0 to 4+. Amyloid grading by both methods
correlated strongly (r = 0.87). Here h-FTAA was positive in 53 of 54 Congo red
positive cases (sensitivity 98%) and h-FTAA was negative in 7 of 17 Congo red
negative controls (specificity 41%), but was also positive for 3 Congo red
negative SA cases. We conclude that h-FTAA fluorescence is more sensitive than
Congo red staining in this small exploratory study of fat tissue samples,
implicating potential sensitivity for prodromal amyloidosis, but is less specific
for clinical amyloidosis defined by Congo red positivity. Given its simplicity h
FTAA staining may therefore be the most appropriate method for rapid screening of
fat tissue samples but should presently treat grade 1+ as only suggestive,
whereas 2+ or higher as positive for amyloidosis. Parallel assessment of h-FTAA
and Congo red staining appears highly promising for clinical applications.
PMID- 25847118
TI - Methyl aminolevulinate photodynamic therapy for actinic keratosis does not affect
peripheral regulatory T-cell level or function.
PMID- 25847123
TI - SirT1 and STAT3 protect retinal pigmented epithelium cells against oxidative
stress.
AB - It has been previously demonstrated that there are interactions between sirtuin 1
(SirT1) and signal transducer and activator of transcription 3 (STAT3), which
have versatile roles in various microenvironments. However, whether or not there
is crosstalk between these two molecules during oxidative stress, and what
mechanism of crosstalk occurs in retinal pigmented epithelium cells (RPEs), the
protection of which may delay the process of age-related macular degeneration
(AMD), has required further elucidation. The present study aimed to investigate
the interactions between SirT1 and STAT3 in RPEs, following exposure to oxidative
stress. The rates of proliferation and apoptosis, levels of intracellular
reactive oxygen species and cell senescence of RPEs, induced by oxidants [H2O2
and oxidized low density lipoprotein (oxLDL)], were evaluated. The results
revealed a downregulation of SirT1 expression, and an upregulation of STAT3
expression during oxidative stress. Further investigation indicated that SirT1
protected RPEs from oxidative stress-induced damage. Furthermore, gain- and loss
of-function experiments indicated that SirT1 had negative effects on the
regulation of STAT3 expression in RPEs during oxidative stress. Notably, STAT3
directly protected the cells from oxidative stress, rather than depending on
SirT1. Additionally, the protective effects of STAT3 had no association with the
modulation of cell senescence during oxidative stress. In conclusion, SirT1 had
negative effects on the regulation of STAT3 expression during oxidative stress.
However, SirT1 and STAT3 demonstrated protective roles against oxidative stress
in RPEs. These results therefore suggested that there was an equilibrium
mechanism between SirT1 and STAT3 against oxidative stress, meaning that an
equilibrium mechanism is required to be considered when combined application of
STAT3 and SirT1 were performed to treat AMD.
PMID- 25847124
TI - A poly(lactide-co-glycolide) film loaded with abundant bone morphogenetic protein
2: A substrate-promoting osteoblast attachment, proliferation, and
differentiation in bone tissue engineering.
AB - We explored a novel biodegradable poly(lactide-co-glycolide) (PLGA) film loaded
with over 80 wt % bone morphogenetic protein (BMP)-2, which was regarded as a
substrate-promoting osteoblast attachment, proliferation, and differentiation for
application of bone tissue engineering. Using phospholipid as a surfactant, BMP-2
was modified as a complex (PBC) for dispersing in PLGA/dichloromethane solution.
The PLGA film loaded with BMP-2 and phospholipid complex (PBC-PF) showed rough
and draped morphology with high entrapment efficiency exceeding 80% and good
hydrophilicity, respectively. The in vitro release study of BMP-2 showed that
about 50% BMP-2 was slowly and continuously released from PBC-PF within 5 weeks
and had a short initial burst release only in the last 1.5 days, which was better
than serious burst release of PLGA film loaded with pure BMP-2 without
phospholipid (BMP-PF) as control. By comparison with other PLGA films and tissue
culture plates, it was confirmed that PBC-PF significantly promoted the
attachment, proliferation, and differentiation of osteoblasts with higher
entrapment efficiency and better sustained release. These advantages illustrated
that PBC-PF could be a potential substrate providing long-term requisite growth
factors for osteoblasts, which might be applied in bone tissue engineering.
PMID- 25847125
TI - DNA damage and S phase arrest induced by Ochratoxin A in human embryonic kidney
cells (HEK 293).
AB - Ochratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic,
hepatotoxic and immunotoxic effects. The mechanisms underlying the nephrotoxicity
of OTA remain obscure. To investigate DNA damage and the changes of the cell
cycle distribution induced by OTA, human embryonic kidney cells (HEK 293 cells)
were incubated with various concentrations of OTA for 24h in vitro. The results
indicated that OTA treatment led to the production of reactive oxygen species
(ROS) and to a decrease of the mitochondrial membrane potential (DeltaPsim). OTA
induced DNA damage in HEK 293 cells was evidenced by DNA comet tails formation
and increased expression of gamma-H2AX. In addition, OTA could induce cell cycle
arrest at the S phase in HEK 293 cells. The expression of key cell cycle
regulatory factors that were critical to the S phase, including cyclin A2, cyclin
E1, and CDK2, were further detected. The expression of cyclin A2, cyclin E1, and
CDK2 were significantly decreased by OTA treatment at both the mRNA and protein
levels. The apoptosis of HEK 293 cells after OTA treatment was observed using
Hoechst 33342 staining. The results confirmed that OTA did induce apoptosis in
HEK 293 cells. In conclusion, our results provided new insights into the
molecular mechanisms by which OTA might promote nephrotoxicity.
PMID- 25847126
TI - Multi-functional ion-sensor based on a photochromic diarylethene with a 1H
imidazo [4,5-f][1,10] phenanthroline unit.
AB - A new asymmetrical diarylethene containing a 1H-imidazo [4,5-f][1,10]
phenanthroline unit was synthesized. The compound showed typical photochromism
and functioned as a notable fluorescence switch upon alternating irradiation with
ultraviolet (UV) and visible light. Its closed-ring isomer could be used as a
selective 'naked-eye' colorimetric sensor for Cu(2+), accompanied by a notable
color change from blue to colorless. Furthermore, the compound was found to be
selective towards Ca(2+), Mg(2+), and Sr(2+) with significant fluorescence
changes. On the basis of this characteristic, a logic circuit was constructed by
utilizing both light and chemical stimuli as inputs and fluorescence intensity at
487 nm as output.
PMID- 25847127
TI - Magnetic controlling of migration of DNA and proteins using one-step modified
gold nanoparticles.
AB - A protocol was developed for preparing magnetic gold nanoparticles via one-step
modification with a paramagnetic cationic surfactant. These magnetic gold
nanoparticles can bind to and manipulate a low strength magnetic field-based
delivery of DNA and proteins powerfully and non-invasively.
PMID- 25847128
TI - Detection and partial characterization of antifungal bioactivity from the
secretions of the medicinal maggot, Lucilia sericata.
AB - The antibacterial properties of the excretions/secretions (ES) of the medicinal
maggot, Lucilia sericata have long been known and the effectiveness of maggot
debridement therapy in relation to the clearance of bacteria from the surface of
wounds has been the source of much research over recent years. Less well known,
however, are the antifungal properties of L. sericata ES. Here, we show by means
of the colony forming unit assay and optical density assays, that L. sericata
native ES possess significant antifungal properties and appears to possess a
highly heat stable, freeze/thaw, and lyophilization resistant antifungal
component. We also show that the antifungal activity present in the native ES
consists of a number of antifungal components present in three fraction masses
consisting of >10, 10-0.5, and <0.5 kDa, with the greatest level of activity
being seen in the <0.5 kDa fraction.
PMID- 25847129
TI - Cyclone performances depend on multiple factors: comments on "A CFD study of the
effect of cyclone size on its performance parameters" by Mehdi Azadi et al.
(2010).
PMID- 25847131
TI - Intrapleural alteplase decreases parapneumonic effusion volume in children more
than saline irrigation.
AB - OBJECTIVE: In this prospective, double-blind, randomized crossover trial, we
determined the effect of intrapleural fibrinolysis with alteplase compared to
that of normal saline irrigation on the thoracostomy tube output and pleural
effusion volume in children with complicated parapneumonic effusion. METHODS:
Twenty seven children, median age 3.5 years, referred to the interventional
radiology service for thoracostomy tube drainage of a parapneumonic effusion were
studied. Seventeen patients with pleural fluid thickness greater than 2 cm or
>20% ipsilateral chest volume after 8 hr of thoracostomy tube drainage entered
the treatment arm. They were randomized to receive alteplase 0.1 mg/kg twice a
day on days 1 and 3, or on days 2 and 4, with normal saline irrigation on the
alternate days. Daily pleural fluid volume measured by low dose chest computed
tomography (CT) and thoracostomy tube output was compared between the saline and
alteplase groups. RESULTS: Compared to normal saline irrigation, alteplase
irrigation resulted in increased thoracostomy tube drainage and to a greater
decline in pleural fluid volume. Earlier alteplase administration resulted in
increased fluid mobilization compared to administration later in the hospital
course. There were no bleeding complications. CONCLUSIONS: Intrapleural
fibrinolysis with alteplase safely increases pleural drainage and decreases the
volume of pleural inflammatory debris compared to intrapleural administration of
normal saline. The benefit of intrapleural alteplase on decreasing the volume of
pleural inflammatory debris occurs for up to 72 hr with repeated twice daily
dosing.
PMID- 25847130
TI - Pre-transplant antibody screening and anti-CD154 costimulation blockade promote
long-term xenograft survival in a pig-to-primate kidney transplant model.
AB - Xenotransplantation has the potential to alleviate the organ shortage that
prevents many patients with end-stage renal disease from enjoying the benefits of
kidney transplantation. Despite significant advances in other models, pig-to
primate kidney xenotransplantation has met limited success. Preformed anti-pig
antibodies are an important component of the xenogeneic immune response. To
address this, we screened a cohort of 34 rhesus macaques for anti-pig antibody
levels. We then selected animals with both low and high titers of anti-pig
antibodies to proceed with kidney transplant from galactose-alpha1,3-galactose
knockout/CD55 transgenic pig donors. All animals received T-cell depletion
followed by maintenance therapy with costimulation blockade (either anti-CD154
mAb or belatacept), mycophenolate mofetil, and steroid. The animal with the high
titer of anti-pig antibody rejected the kidney xenograft within the first week.
Low-titer animals treated with anti-CD154 antibody, but not belatacept exhibited
prolonged kidney xenograft survival (>133 and >126 vs. 14 and 21 days,
respectively). Long-term surviving animals treated with the anti-CD154-based
regimen continue to have normal kidney function and preserved renal architecture
without evidence of rejection on biopsies sampled at day 100. This description of
the longest reported survival of pig-to-non-human primate kidney
xenotransplantation, now >125 days, provides promise for further study and
potential clinical translation.
PMID- 25847132
TI - The problem of publication-pollution denialism.
PMID- 25847134
TI - Azadirachtin, a neem-derived biopesticide, impairs behavioral and hematological
parameters in carp (Cyprinus carpio).
AB - Azadirachtin (Aza) is a promisor biopesticide used in organic production and
aquaculture. Although this compound is apparently safe, there is evidence that it
may have deleterious effects on fish. Behavioral and hematological tests are
grouped into a set of parameters that may predict potential toxicity of chemical
compounds. Here, we investigate the effects of Aza, in the commercial formulation
NeenmaxTM , on carp (Cyprinus carpio) by defining LC50 (96 h), and testing
behavioral and hematological parameters. In our study, LC50 was estimated at 80
MUL/L. We exposed carp to Aza at 20, 40, and 60 MUL/L, values based on 25, 50,
and 75% of LC50 , respectively. At 60 MUL/L, Aza promoted significant changes in
several parameters, increasing the distance traveled and absolute turn angle. In
addition, the same concentration decreased the time spent immobile and the number
of immobile episodes. Hematological parameters, such as hematocrit, hemoglobin,
hematimetrics index, and red cell distribution, were decreased at 60 MUL/L Aza
exposure. In conclusion, our study demonstrates that 60 MUL/L Aza altered
locomotor activity, motor pattern, and hematological parameters, suggesting
potential toxicity to carp after acute exposure. In addition, this is the first
report that evaluates the actions of a chemical contaminant using automated
behavioral tracking of carp, which may be a useful tool for assessing the
potential toxicity of biopesticides in conjunction with hematological tests. (c)
2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1381-1388, 2016.
PMID- 25847133
TI - RNA pol II transcript abundance controls condensin accumulation at mitotically up
regulated and heat-shock-inducible genes in fission yeast.
AB - Condensin plays fundamental roles in chromosome dynamics. In this study, we
determined the binding sites of condensin on fission yeast (Schizosaccharomyces
pombe) chromosomes at the level of nucleotide sequences using chromatin
immunoprecipitation (ChIP) and ChIP sequencing (ChIP-seq). We found that
condensin binds to RNA polymerase I-, II- and III-transcribed genes during both
mitosis and interphase, and we focused on pol II constitutive and inducible
genes. Accumulation sites for condensin are distinct from those of cohesin and
DNA topoisomerase II. Using cell cycle stage and heat-shock-inducible genes, we
show that pol II-mediated transcripts cause condensin accumulation. First,
condensin's enrichment on mitotically activated genes was abolished by deleting
the sep1(+) gene that encodes an M-phase-specific forkhead transcription factor.
Second, by raising the temperature, condensin accumulation was rapidly induced at
heat-shock protein genes in interphase and even during mid-mitosis. In
interphase, condensin accumulates preferentially during the postreplicative
phase. Pol II-mediated transcription was neither repressed nor activated by
condensin, as levels of transcripts per se did not change when mutant condensin
failed to associate with chromosomal DNA. However, massive chromosome
missegregation occurred, suggesting that abundant pol II transcription may
require active condensin before proper chromosome segregation.
PMID- 25847135
TI - Maintenance of distinct melanocyte populations in the interfollicular epidermis.
AB - Hair follicles and sweat glands are recognized as reservoirs of melanocyte stem
cells (MSCs). Unlike differentiated melanocytes, undifferentiated MSCs do not
produce melanin. They serve as a source of differentiated melanocytes for the
hair follicle and contribute to the interfollicular epidermis upon wounding,
exposure to ultraviolet irradiation or in remission from vitiligo, where
repigmentation often spreads outwards from the hair follicles. It is unknown
whether these observations reflect the normal homoeostatic mechanism of
melanocyte renewal or whether unperturbed interfollicular epidermis can maintain
a melanocyte population that is independent of the skin's appendages. Here, we
show that mouse tail skin lacking appendages does maintain a stable melanocyte
number, including a low frequency of amelanotic melanocytes, into adult life.
Furthermore, we show that actively cycling differentiated melanocytes are present
in postnatal skin, indicating that amelanotic melanocytes are not uniquely relied
on for melanocyte homoeostasis.
PMID- 25847136
TI - Minimally invasive treatment of traumatic high rectovaginal fistulas.
AB - BACKGROUND: We propose a new minimally invasive technique by laparoscopic
approach which minimizes parietal damage and allows precise location of the
fistula, hence reduces blind dissection. METHODS: Ten consecutive patients
suffering from a HRVF benefited from the described technique. Location and time
frame were east of the Democratic Republic of Congo and September 2012 through
January 2014. By laparoscopy, dissection of the mesorectum in the "holy plane" is
taken posteriorly as distally on the sacrum as possible. Dissection subsequently
continues laterally beyond the fistula in an effort to maximally circumvene the
fistulous area where no plane of cleavage can be found. If the cleavage plane
beyond the fistula addresses a healthy rectum, a suture of vaginal and rectal
defect is performed. If the cleavage plane beyond the fistula involves
significant laceration of the rectum, while leaving at least 2 cm of healthy
rectum above the sphincter, rectal resection and colorectal anastomosis are
performed. If the rectal laceration involves the distal 2 cm but halts short of
the sphincter (large fistula), the pull-through technique is performed. RESULTS:
Of ten participants, four had large HRVF and two presented significant fibrosis.
Three underwent simple suture of rectal and vaginal defect, one rectal resection
and six a "pull-through" technique. The median procedure time was 1h50 (1h00
3h30). There was no morbidity. None of the patients required protective ileostomy
or colostomy. Nine patients were declared clinically cured with a median follow
up of 14.3 months (11-36). The Cleveland Clinic Incontinence Score was 20 in all
patients before the treatment and was significantly (p = 0.004) reduced to 2.6 [0
20] after the treatment. CONCLUSIONS: This minimally invasive technique allowed
us to treat HRVF, including complex ones in ten patients without significant
morbidity. Clinical success with a median follow-up of 14.3 months was 90%.
PMID- 25847137
TI - A utility of peroral endoscopic myotomy (POEM) across the spectrum of esophageal
motility disorders.
AB - BACKGROUND: Peroral endoscopic myotomy (POEM) has been performed as a novel
endoscopic procedure to treat achalasia with favorable outcome. The objective of
this study was to assess the outcome of POEM in our initial series and to assess
the safety and efficacy of POEM in a variety of esophageal motility-related
clinical problems. METHODS: This is a retrospective cross-sectional study
involving all patients with esophageal motility disorders defined by the Chicago
classification, who had undergone consideration for POEM at our institution.
Validated questionnaires such as gastroesophageal reflux disease health-related
quality of life (GERD-HRQL), reflux symptom index (RSI) and achalasia disease
specific health-related quality of life were obtained pre- and postoperatively.
RESULTS: From January 2013 to October 2014, a total of 35 POEMs (achalasia n =
25, non-achalasia n = 10) were performed on 33 patients (female n = 20, male n =
13, mean age 56.9 years). There was no mortality. The rate of inadvertent
mucosotomy was 17.1%. The rate of complications requiring interventions was 5.7%.
During a mean follow-up period of 7 months (range 0.5-17), 92% of patients with
achalasia and 75% of those with non-achalasia motility disorders had a
symptomatic improvement in dysphagia. Chest pain was completely resolved in all
patients with achalasia (8/8) and 80% of patients with non-achalasia (4/5). The
GERD-HRQL, RSI and dysphagia scores significantly improved after POEM in patients
with achalasia. There was a significant improvement in GERD-HRQL and RSI scores,
and a trend toward lower dysphagia score in patients with non-achalasia.
CONCLUSIONS: The outcome of POEM to treat achalasia and non-achalasia motility
disorders is consistent with previous studies. Potential benefit of POEM includes
not only its flexibility to adjust the length and location of myotomy but also
the ability to extend myotomy proximally without thoracoscopy or thoracotomy.
POEM can be combined with laparoscopic procedures and used as "salvage" for
localized esophageal dysmotility.
PMID- 25847138
TI - Patients with psychiatric comorbidity can safely undergo bariatric surgery with
equivalent success.
AB - INTRODUCTION: Patients with psychiatric disorder were reported to have a poor
outcome in bariatric surgery. Few studies have examined the outcome of
laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding
(LAGB) in patients with psychiatric history. We aimed to compare excess weight
loss (%EWL) in patients with and without psychiatric comorbidities who underwent
LSG or LAGB. METHODS: Patients undergoing LSG or LAGB were identified from our
prospective database. A multidisciplinary team evaluated all patients
preoperatively, including a psychological evaluation. Patients with the diagnosis
of depression, anxiety, bipolar disorder, and schizophrenia were included in the
psychiatric comorbidity group (PSY). Others were included in group NON-PSY. All
patients were first screened to be psychologically stable to undergo surgery.
Initial BMI and %EWL at 3, 6, and 12 months postoperatively were compared.
RESULTS: A total of 590 patients (81.4 % women), with a median BMI of 43.8
kg/m(2) (range 30-99) who underwent LSG (n = 222) or LAGB (n = 368) from January
2006 to June 2013, were identified. Psychiatric comorbidities that were well
controlled at the time of surgery were found in 188 patients (31.9%). Diagnostic
criteria for depression were met in 154 patients (26.1%), 75 patients suffered
from anxiety (12.7%), 9 from bipolar disorder, and 4 from schizophrenia (0.7%).
Initial BMI was not different between the two groups. No significant difference
in %EWL between the groups was found during follow-up (44.13 vs. 43.37%EWL,
respectively, at 1 year; p = 0.76). When LSG and LAGB patients were analyzed as
subsets, again no difference in %EWL at 1 year was found for PSY vs. NON-PSY
(LSG: 51.56 vs. 54.86%EWL; LAGB: 38.48 vs. 38.45%EWL, all p = ns). In
multivariate analysis, the differences from unadjusted analysis persisted.
CONCLUSION: These findings demonstrate that a similar %EWL can be achieved in
patients undergoing LSG or LAGB despite the presence of well-controlled
psychiatric comorbidity.
PMID- 25847139
TI - Robotic versus laparoscopic surgery for colonic disease: a meta-analysis of
postoperative variables.
AB - INTRODUCTION: An increasing number of studies have been published since the
introduction of robotic technology into general surgery. Gastrointestinal surgery
is an area of special interest for the robotic surgeon. Colonic surgery can be
challenging depending on the disease and the operative approach. We seek to
perform a meta-analysis comparing robotic surgery against laparoscopic surgery in
this particular field. MATERIALS AND METHODS: We performed a systematic search of
MEDLINE database from January 2001 to July 2013 supplemented by manual searches
of bibliographies of key relevant articles. Randomized controlled trials and
cohort studies were selected for review and for collection of postoperative data
(length of stay, time to first flatus and complications). RESULTS: After careful
review, nine studies were considered for analysis. Non-pooled data showed a
slight trend toward laparoscopy with increased number of events without
statistical significance. Pooled data demonstrated a statistical significance for
return to bowel function in the right and mixed robotic colectomy arm (WSMD
0.33, 95 % CI -0.5, -0.1; p < 0.005 and WSMD -0.26, 95 % CI -0.51, 0.0; p =
0.05). Pooled data of length of stay and complications showed no statistical
significance between robotic and laparoscopic colonic surgery. DISCUSSION:
Robotic surgery is a comparable option when dealing with colonic disease, either
benign or malignant. No difference in complication rate or length of stay was
found when comparing the two. Robotic surgery appears to have an advantage over
laparoscopy in regards to return of bowel function when dealing with right
colectomies.
PMID- 25847140
TI - Age-related sensitivity to endotoxin-induced liver inflammation: Implication of
inflammasome/IL-1beta for steatohepatitis.
AB - Aging is associated with increased vulnerability to inflammatory challenge.
However, the effects of altered inflammatory response on the metabolic status of
tissues or organs are not well documented. In this study, we present evidence
demonstrating that lipopolysaccharide (LPS)-induced upregulation of the
inflammasome/IL-1beta pathway is accompanied with an increased inflammatory
response and abnormal lipid accumulation in livers of aged rats. To monitor the
effects of aging on LPS-induced inflammation, we administered LPS (2 mg kg(-1) )
to young (6-month old) and aged (24-month old) rats and found abnormal lipid
metabolism in only aged rats with increased lipid accumulation in the liver. This
lipid accumulation in the liver was due to the dysregulation of PPARalpha and
SREBP1c. We also observed severe liver inflammation in aged rats as indicated by
increased ALT levels in serum and increased Kupffer cells in the liver.
Importantly, among many inflammation-associated factors, the aged rat liver
showed chronically increased IL-1beta production. Increased levels of IL-1beta
were caused by the upregulation of caspase-1 activity and inflammasome
activation. In vitro studies with HepG2 cells demonstrated that treatment with IL
1beta significantly induced lipid accumulation in hepatocytes through the
regulation of PPARalpha and SREBP1c. In summary, we demonstrated that LPS-induced
liver inflammation and lipid accumulation were associated with a chronically
overactive inflammasome/IL-1beta pathway in aged rat livers. Based on the present
findings, we propose a mechanism of aging-associated progression of
steatohepatitis induced by endotoxin, delineating a pathogenic role of the
inflammasome/IL-1beta pathway involved in lipid accumulation in the liver.
PMID- 25847141
TI - Telomerase reverse transcriptase promoter methylation is related to a risk of
recurrence in hepatocellular carcinoma.
PMID- 25847142
TI - Autophagic adaptation is associated with exercise-induced fibre-type shifting in
skeletal muscle.
AB - AIM: Acute exercise is known to activate autophagy in skeletal muscle. However,
little is known about how basal autophagy in skeletal muscle adapts to chronic
exercise. In the current study we aim to, firstly, examine whether long-term
habitual exercise alters the basal autophagic signalling in plantaris muscle and,
secondly, examine the association between autophagy and fibre-type shifting.
METHODS: Adult female Sprague-Dawley rats aged 2 months were randomly assigned to
control and exercise groups. Animals in exercise group were kept in cages
equipped with free access running wheels to perform habitual exercise for 5
months. Animals in the control group were caged in the absence of running wheels.
Animals were sacrificed after the 5-month experimental period. Plantaris muscle
tissues were harvested for analysis. RESULTS: We showed that long-term habitual
exercise enhanced basal autophagy, but without altering expressions of autophagy
proteins in plantaris muscle. Interestingly, sirtuin protein, a possible
regulator of autophagy, was upregulated in plantaris muscle. Furthermore, we
suspected that different types of muscle fibre adapted to chronic exercise in
different ways. Long-term habitual exercise resulted in fibre-type shifting from
type IIX to IIA in both gastrocnemius muscle and plantaris muscle. Intriguingly,
our analysis demonstrated that LC3-II protein abundance is positively correlated
with the proportion of type IIA fibre whereas it was negatively correlated with
the proportion of type IIX fibre in plantaris muscle. PGC-1alpha protein
abundance was positively associated with the proportion of type IIA fibre and LC3
II in plantaris muscle. CONCLUSION: These results suggest that basal autophagy is
enhanced in plantaris muscle after long-term habitual exercise and associated
with fibre-type shifting.
PMID- 25847143
TI - Analysis of signal processing in vestibular circuits with a novel light-emitting
diodes-based fluorescence microscope.
AB - Optical visualization of neural network activity is limited by imaging system
dependent technical tradeoffs. To overcome these constraints, we have developed a
powerful low-cost and flexible imaging system with high spectral variability and
unique spatio-temporal precision for simultaneous optical recording and
manipulation of neural activity of large cell groups. The system comprises eight
high-power light-emitting diodes, a camera with a large metal-oxide-semiconductor
sensor and a high numerical aperture water-dipping objective. It allows fast and
precise control of excitation and simultaneous low noise imaging at high
resolution. Adjustable apertures generated two independent areas of variable size
and position for simultaneous optical activation and image capture. The
experimental applicability of this system was explored in semi-isolated
preparations of larval axolotl (Ambystoma mexicanum) with intact inner ear organs
and central nervous circuits. Cyclic galvanic stimulation of semicircular canals
together with glutamate- and gamma-aminobutyric acid (GABA)-uncaging caused a
corresponding modulation of Ca(2+) transients in central vestibular neurons.
These experiments revealed specific cellular properties as well as synaptic
interactions between excitatory and inhibitory inputs, responsible for spatio
temporal-specific sensory signal processing. Location-specific GABA-uncaging
revealed a potent inhibitory shunt of vestibular nerve afferent input in the
predominating population of tonic vestibular neurons, indicating a considerable
impact of local and commissural inhibitory circuits on the processing of
head/body motion-related signals. The discovery of these previously unknown
properties of vestibular computations demonstrates the merits of our novel
microscope system for experimental applications in the field of neurobiology.
PMID- 25847144
TI - Association between the expression of T-cadherin and vascular endothelial growth
factor and the prognosis of patients with gastric cancer.
AB - T-cadherin has been identified as a tumor-suppressor gene in several types of
cancer. The present study aimed to investigate the association of the expression
of T-cadherin with angiogenesis, and to evaluate its prognostic value for
patients with primary gastric cancer. Gastric cancer tissues and matched adjacent
tissues from 166 patients receiving surgical resection were included in the
present study. The expression of T-cadherin was detected using
immunohistochemistry, western blotting and reverse transcription-quantitative
polymerase chain reaction. The expression of vascular epidermal growth factor
(VEGF) was detected using immunohistochemistry, and its association with the
expression of T-cadherin was analyzed. In addition, the association between the
expression of T-cadherin and clinicopathological features were analyzed. The mRNA
and protein expression levels of T-cadherin were significantly lower in the
gastric cancer tissue compared with the corresponding adjacent normal tissue
(P<0.05). The expression of VEGF was not associated with the expression of T
cadherin in the gastric cancer tissue. The decreased protein expression of T
cadherin correlated with smoking, larger tumor size (diameter, >4 cm), lymph node
metastasis and a higher tumor-lymph node-metastasis stage (P<0.05 or P<0.01).
However, the expression of T-cadherin was not correlated with gender, age,
alcohol intake, Helecobacter pylori infection or differentiation (P>0.05). The
multivariate analysis demonstrated that the expression of T-cadherin was an
independent prognostic factor for the overall survival rate of patients with
gastric cancer. This data suggested that the downregulation of T-cadherin may
contribute to gastric cancer progression, representing a useful biomarker for
predicting the biological behavior and prognosis of gastric cancer. However, no
significant association was observed between the expression of VEGF and T
cadherin.
PMID- 25847145
TI - Evolution of cooperation in a multidimensional phenotype space.
AB - The emergence of cooperation in populations of selfish individuals is a
fascinating topic that has inspired much theoretical work. An important model to
study cooperation is the phenotypic model, where individuals are characterized by
phenotypic properties that are visible to others. The phenotype of an individual
can be represented for instance by a vector x = (x1,...,xn), where x1,...,xn are
integers. The population can be well mixed in the sense that everyone is equally
likely to interact with everyone else, but the behavioral strategies of the
individuals can depend on their distance in the phenotype space. A cooperator can
choose to help other individuals exhibiting the same phenotype and defects
otherwise. Cooperation is said to be favored by selection if it is more abundant
than defection in the stationary state. This means that the average frequency of
cooperators in the stationary state strictly exceeds 1/2. Antal et al. (2009c)
found conditions that ensure that cooperation is more abundant than defection in
a one-dimensional (i.e. n = 1) and an infinite-dimensional (i.e. n = infinity)
phenotype space in the case of the Prisoner's Dilemma under weak selection.
However, reality lies between these two limit cases. In this paper, we derive the
corresponding condition in the case of a phenotype space of any finite dimension.
This is done by applying a perturbation method to study a mutation-selection
equilibrium under weak selection. This condition is obtained in the limit of a
large population size by using the ancestral process. The best scenario for
cooperation to be more likely to evolve is found to be a high population-scaled
phenotype mutation rate, a low population-scaled strategy mutation rate and a
high phenotype space dimension. The biological intuition is that a high
population-scaled phenotype mutation rate reduces the quantity of interactions
between cooperators and defectors, while a high population-scaled strategy
mutation rate introduces newly mutated defectors that invade groups of
cooperators. Finally it is easier for cooperation to evolve in a phenotype space
of higher dimension because it becomes more difficult for a defector to migrate
to a group of cooperators. The difference is significant from n = 1 to n = 2 and
from n = 2 to n = 3, but becomes small as soon as n >= 3.
PMID- 25847146
TI - Posttonsillectomy weight loss in adults.
AB - OBJECTIVE: To analyze and determine the incidence and severity of weight loss in
adult tonsillectomies. STUDY DESIGN: Case series with chart review. SETTING:
Adult tonsillectomy is performed for a variety of indications. Anecdotally,
patients report a 10- to 15-pound weight loss in the postoperative period;
however, no supporting research has been documented. The pediatric population has
a well-documented weight gain postoperatively. SUBJECTS: In total, 138 adults
(aged 18-40 years) receiving tonsillectomy at Naval Medical Center Portsmouth
(NMCP) between 2008 and 2013. METHODS: A retrospective study was performed using
an S3 surgery scheduling system search of all adult tonsillectomies at NMCP
between 2008 and 2013. A subsequent electronic medical record search (AHLTA) of
preoperative and postoperative weights and demographics was performed. RESULTS:
Data analysis revealed a significant difference found between preoperative and
postoperative weight across all age groups (4.77 pounds, P < .005). Analysis of
variance was performed to determine if there is a significant difference between
these age and body mass index (BMI) groups. The highest amount of weight loss was
observed in the oldest population group (5.72 pounds in subjects aged >40 years,
4.95 pounds in 31- to 40-year-olds, and 5.44 pounds in 20- to 30-year-olds, P =
.03). Age comparisons were statistically significant. There was no statistically
significant association between BMI and postoperative weight loss. CONCLUSIONS:
These results indicate that there is evidence of a roughly 5-pound weight loss in
the postoperative period following tonsillectomy in adults with subsequent return
to baseline weight after roughly 5 months. These findings are significant since
this could lead to further research into changes in obesity-associated disease.
PMID- 25847147
TI - Parathyroid Localization and Preservation during Transcervical Resection of
Substernal Thyroid Glands.
AB - OBJECTIVE: The feasibility of parathyroid preservation during thyroidectomy has
not been well documented for cases in which the thyroid gland extends into the
mediastinum. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic
referral center. SUBJECTS AND METHODS: In this retrospective cohort study, 70
consecutive patients who had substernal thyroid glands treated with a
transcervical thyroidectomy between 1993 and 2013 were compared with 286
thyroidectomies that did not entail substernal extension within that same time
period. All localized parathyroid glands were confirmed histologically. RESULTS:
Of 160 possible parathyroid glands in the substernal cases, 119 (74%) were
histologically confirmed intraoperatively (67 superior and 52 inferior). In
nonsubsternal cases, 725 (89%) were histologically confirmed (372 superior and
353 inferior). There was a statistically significant difference between the
substernal and nonsubsternal cases in the total number of glands found (P <
.0001) and the number of superior and inferior glands that were identified (P =
.009 and < 0.0001). CONCLUSIONS: Even when the thyroid gland extends into the
mediastinum, it is often possible, although with reduced efficiency, to identify
and preserve the parathyroid glands.
PMID- 25847148
TI - Reliability and accuracy of simple visual estimation in assessment of peripheral
arterial stenosis.
AB - PURPOSE: To evaluate reliability, accuracy, and agreement of simple visual
estimation (SVE) in determining the degree of peripheral arterial stenosis
compared with calibrated measurements. MATERIALS AND METHODS: In 2 sessions, 23
interventionists with a wide range of experience and subspecialty training
reviewed 42 angiographic images of lower extremity and carotid arteries (21
iliofemoral arteries and 21 carotid arteries). An independent physician measured
all lesions using manual calipers. Intrarater and interrater reliability were
assessed by intraclass correlation. A +/- 5% error was considered the threshold
for accuracy, and weighted kappa statistics were computed to assess agreement
with respect to the degree of stenosis (< 50%, nonsignificant; 50%-80%,
significant; > 80%, severe). RESULTS: Intrarater reliability of SVE was 0.99, and
interrater reliability was 0.83. Accuracy varied from 52.8% for images of severe
stenosis to 26.5% and 18.1% for significant and nonsignificant stenosis,
respectively (P < .001). Agreement between SVE and caliper with regard to degree
of stenosis was good (weighted kappa 0.56) overall with correct classification
ranging from 92.6% for severe stenosis to 53.4% and 68.2% for significant and
nonsignificant stenosis, respectively (P < .001). Misclassification of
nonsignificant and significant stenosis was more frequent for carotid arteries
than for lower extremities. CONCLUSIONS: Despite high reliability, SVE of
peripheral arterial stenosis has limited accuracy in determining the exact degree
of stenosis. Although severe stenosis is readily identified by SVE, arterial
stenosis of < 80% is frequently overestimated, especially for carotid arteries,
and should be confirmed by caliper assessment.
PMID- 25847149
TI - Endovenous Laser Ablation of Perforating Veins: Feasibility, Safety, and
Occlusion Rate Using a 1,470-nm Laser and Bare-Tip Fiber.
AB - PURPOSE: To describe technical feasibility and safety of perforating vein
ablation with the use of a 1,470-nm laser and bare-tip fiber in the management of
chronic venous insufficiency (CVI). MATERIALS AND METHODS: A total of 171
perforating veins were ablated in 101 limbs of 87 patients (mean age, 54.4 y; 79%
female). Outcomes included sonographic occlusion of ablated perforator,
subjective changes of insufficiency symptoms, incidence of procedure-related side
effects (pain, hyperpigmentation), and complications (burn, infection, deep vein
thrombosis, paresthesia). Correlation between perforator closure and patient
symptoms was assessed by Pearson chi(2) test. Factors influencing failure of
perforator closure were analyzed by analysis of variance. RESULTS: Forty-nine
perforating veins had previous great saphenous vein (GSV) interruption, 25 had
previous small saphenous vein (SSV) interruption, 88 had previous GSV and SSV
interruption, and 9 had competent saphenous systems. Ninety-one ablations were
combined with microphlebectomy, 55 were combined with sclerotherapy, and 25 were
performed alone. At 1 and 3 months' follow-up, 94% and 98% of ablated perforators
were sonographically occluded, and 82% and 96% of patients noted complete symptom
resolution, respectively. Complications included 5 cases of new-onset paresthesia
and 1 case of nonocclusive deep vein thrombosis. Ablation failed in 10
perforators, and treatment failure showed significant correlations with higher
clinical, etiology, anatomy, and physiology score (P = .002) and history of
GSV/SSV interruption (P = .042). CONCLUSIONS: Three-month closure of perforating
veins is achievable by using a 1,470-nm laser and bare-tip fiber and can be
safely performed alone or in combination with microphlebectomy or sclerotherapy
at all stages of CVI severity.
PMID- 25847150
TI - Tumor necrosis factor-alpha is a potential diagnostic biomarker for chronic
neuropathic pain after spinal cord injury.
AB - Neuropathic pain (NP) is one of the most common complications after spinal cord
injury (SCI), but no protein biomarkers has ever been introduced into clinical
diagnosis. Previous studies implicated that toll-like receptor (TLR) 4 played a
critical role in the development of NP in animal SCI models. Here, a total of 140
participants were recruited, 70 of them were SCI-NP subject and the rest 70
controls did not show neuropathic symptoms. TLR4 was upregulated significantly in
SCI-NP patients compared with SCI-noNP subjects. Furthermore, we measured the
concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL
6), two TLR4 downstream pro-inflammatory cytokines, to assess their diagnostic
values. Receiver operating characteristics (ROC) analysis revealed that TNF-alpha
had great potential advantages to predict the progression of neuropathy, the
risks of NP were strongly increased in SCI subjects with higher levels of TNF
alpha (odds ratio: 4.92; 95% confidence interval: 1.89-12.32). These results
suggested neuro-immune activation contributed to the development of neuropathic
disorder after SCI, and TNF-alpha could be a potential sensitive diagnostic
biomarker for chronic neuropathic pain in SCI patients.
PMID- 25847151
TI - Mitochondrial dynamics and inherited peripheral nerve diseases.
AB - Peripheral nerves have peculiar energetic requirements because of considerable
length of axons and therefore correct mitochondria functioning and distribution
along nerves is fundamental. Mitochondrial dynamics refers to the continuous
change in size, shape, and position of mitochondria within cells. Abnormalities
of mitochondrial dynamics produced by mutations in proteins involved in
mitochondrial fusion (mitofusin-2, MFN2), fission (ganglioside-induced
differentiation-associated protein-1, GDAP1), and mitochondrial axonal transport
usually present with a Charcot-Marie-Tooth disease (CMT) phenotype. MFN2
mutations cause CMT type 2A by altering mitochondrial fusion and trafficking
along the axonal microtubule system. CMT2A is an axonal autosomal dominant CMT
type which in most cases is characterized by early onset and rather severe
course. GDAP1 mutations also alter fission, fusion and transport of mitochondria
and are associated either with recessive demyelinating (CMT4A) and axonal CMT (AR
CMT2K) and, less commonly, with dominant, milder, axonal CMT (CMT2K). OPA1 (Optic
Atrophy-1) is involved in fusion of mitochondrial inner membrane, and its
heterozygous mutations lead to early-onset and progressive dominant optic atrophy
which may be complicated by other neurological symptoms including peripheral
neuropathy. Mutations in several proteins fundamental for the axonal transport or
forming the axonal cytoskeleton result in peripheral neuropathy, i.e., CMT,
distal hereditary motor neuropathy (dHMN) or hereditary sensory and autonomic
neuropathy (HSAN), as well as in hereditary spastic paraplegia. Indeed,
mitochondrial transport involves directly or indirectly components of the kinesin
superfamily (KIF5A, KIF1A, KIF1B), responsible of anterograde transport, and of
the dynein complex and related proteins (DYNC1H1, dynactin, dynamin-2),
implicated in retrograde flow. Microtubules, neurofilaments, and chaperones such
as heat shock proteins (HSPs) also have a fundamental role in mitochondrial
transport and mutations in some of related encoding genes cause peripheral
neuropathy (TUBB3, NEFL, HSPB1, HSPB8, HSPB3, DNAJB2). In this review, we address
the abnormalities in mitochondrial dynamics and their role in determining CMT
disease and related neuropathies.
PMID- 25847152
TI - Stochastic activation among inspiratory cells in the pre-Botzinger complex of the
rat medulla revealed by Ca(2+) imaging.
AB - In the pre-Botzinger complex of the ventral medulla (preBotC), a variable pattern
of inspiratory neuronal output and synchronous activation of inspiratory cells
can be observed. However, it is not well known whether cellular activation
patterns among inspiratory cells are variable or fixed. Here, we evaluated the
activation sequence of inspiratory cells during individual rhythmic bursts using
calcium imaging. Onset timing and peak timing of calcium fluctuations during
rhythmic bursts in individual inspiratory cells were used to evaluate the
activation sequence. The sequences of both timings changed stochastically in
individual rhythmic bursts, although the sequences differed between the two
timings even within the same rhythmic burst. The weak correlation between these
two timings might indicate that the two parameters reflect different
physiological events. Furthermore, a subset of inspiratory cells was found to
initially activate in the sequences of successive rhythmic bursts. These results
suggest that rhythmic activation of inspiratory cells occurs with a degree of
loose regularity but is not invariable with respect to the sequence of either
onset or peak timing.
PMID- 25847153
TI - Downregulation of the microtubule associated protein tau impairs process
outgrowth and myelin basic protein mRNA transport in oligodendrocytes.
AB - Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their
numerous membranous extensions, which enwrap neuronal axons and form myelin
sheaths. During differentiation oligodendrocytes pass different morphological
stages, downregulate the expression of the proteoglycan NG2, and acquire major
myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid
protein. MBP mRNA is transported in RNA granules along the microtubules (MTs) to
the periphery and translated locally. MTs participate in the elaboration and
stabilization of the myelin forming extensions and are essential for cellular
sorting processes. Their dynamic properties are regulated by microtubule
associated proteins (MAPs). The MAP tau is present in oligodendrocytes and
involved in the regulation and stabilization of the MT network. To further
elucidate the functional significance of tau in oligodendrocytes, we have
downregulated tau by siRNA technology and studied the effects on cell
differentiation and neuron-glia contact formation. The data show that tau
knockdown impairs process outgrowth and leads to a decrease in MBP expression.
Furthermore, MBP mRNA transport to distant cellular extensions is impaired and
cells remain in the NG2 stage. In myelinating cocultures with dorsal root
ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral
knockdown develop into NG2 positive cells with very long and thin processes,
contacting axons loosely, but fail to form internodes. This demonstrates that tau
is important for MBP mRNA transport and involved in process formation. The
disturbance of the balance of tau leads to abnormalities in oligodendrocyte
differentiation, neuron-glia contact formation and the early myelination process.
PMID- 25847155
TI - Label-free colorimetric sensor for mercury(II) and DNA on the basis of
mercury(II) switched-on the oxidase-mimicking activity of silver nanoclusters.
AB - In this paper, a novel colorimetric biosensor for Hg(2+) and DNA molecules is
presented based on Hg(2+) stimulated oxidase-like activity of bovine serum
albumin protected silver clusters (BSA-Ag NCs). Under mild conditions, Hg(2+)
activated BSA-Ag NCs to show high catalytic activity toward the oxidation of
3,3',5, 5'-tetramethylbenzidine (TMB) using ambient dissolved oxygen as an
oxidant. The oxidase-like activity of BSA-Ag NCs was "switched-on" selectively in
the presence of Hg(2+), which permitted a novel and facile colorimetric sensor
for Hg(2+). As low as 25 nmol L(-1)Hg(2+) could be detected with a linear range
from 80 nmol L(-1) to 50 mmol L(-1). In addition, the sensing strategy was also
employed to detect DNA molecules. Hg(2+) is known to bind very strongly and
specifically with two DNA thymine bases (T) to form thymine-Hg(2+)-thymine (T
Hg(2+)-T) base pairs. The hairpin-structure was disrupted and Hg(2+) ions were
released after hybridization with the DNA target. By coupling the Hg(2+) switched
on the oxidase-mimicking activity of BSA-Ag NCs, we developed a novel label-free
strategy for facile and fast colorimetric detection of DNA molecules. More
important, target DNA can be detected as low as 10 nmol L(-1) with a linear range
from 30 to 225 nmol L(-1). Compared with other methods, this method presents
several advantages such as the independence of hydrogen peroxide, high
sensitivity and good selectivity, avoiding any modification or immobilization of
DNA, which holds a great potential of metal NCs for clinical application in
biosensing and biotechnology.
PMID- 25847156
TI - Simultaneous determination of mercury and organic carbon in sediment and soils
using a direct mercury analyzer based on thermal decomposition-atomic absorption
spectrophotometry.
AB - The purpose of this work was to study the feasibility of using a direct mercury
analyzer (DMA) to simultaneously determine mercury (Hg) and organic matter
content in sediment and soils. Organic carbon was estimated by re-weighing the
sample boats post analysis to obtain loss-on-ignition (LOI) data. The DMA-LOI
results were statistically similar (p<0.05) to the conventional muffle furnace
approach. A regression equation was developed to convert DMA-LOI data to total
organic carbon (TOC), which varied between 0.2% and 13.0%. Thus, mercury
analyzers based on combustion can provide accurate estimates of organic carbon
content in non-calcareous sediment and soils; however, weight gain from moisture
(post-analysis), measurement uncertainty, and sample representativeness should
all be taken into account. Sediment cores from seasonal wetland and open water
areas from six oxbow lakes in the Mississippi River alluvial flood plain were
analyzed. Wetland sediments generally had higher levels of Hg than open water
areas owing to a greater fraction of fine particles and higher levels of organic
matter. Annual loading of Hg in open water areas was estimated at 4.3, 13.4,
19.2, 20.7, 129, and 135 ng cm(-2) yr(-1) for Beasley, Roundaway, Hampton,
Washington, Wolf and Sky Lakes, respectively. Generally, the interval with the
highest Hg flux was dated to the 1960s and 1970s.
PMID- 25847157
TI - Large-scale identification of potential drug targets based on the topological
features of human protein-protein interaction network.
AB - Identifying potential drug target proteins is a crucial step in the process of
drug discovery and plays a key role in the study of the molecular mechanisms of
disease. Based on the fact that the majority of proteins exert their functions
through interacting with each other, we propose a method to recognize target
proteins by using the human protein-protein interaction network and graph theory.
In the network, vertexes and edges are weighted by using the confidence scores of
interactions and descriptors of protein primary structure, respectively. The
novel network topological features are defined and employed to characterize
protein using existing databases. A widely used minimum redundancy maximum
relevance and random forests algorithm are utilized to select the optimal feature
subset and construct model for the identification of potential drug target
proteins at the proteome scale. The accuracies of training set and test set are
89.55% and 85.23%. Using the constructed model, 2127 potential drug target
proteins have been recognized and 156 drug target proteins have been validated in
the database of drug target. In addition, some new drug target proteins can be
considered as targets for treating diseases of mucopolysaccharidosis, non
arteritic anterior ischemic optic neuropathy, Bernard-Soulier syndrome and pseudo
von Willebrand, etc. It is anticipated that the proposed method may became a
powerful high-throughput virtual screening tool of drug target.
PMID- 25847158
TI - Enzyme-free surface plasmon resonance aptasensor for amplified detection of
adenosine via target-triggering strand displacement cycle and Au nanoparticles.
AB - Herein, we combine the advantage of aptamer technique with the amplifying effect
of an enzyme-free signal-amplification and Au nanoparticles (NPs) to design a
sensitive surface plasmon resonance (SPR) aptasensor for detecting small
molecules. This detection system consists of aptamer, detection probe (c-DNA1)
partially hybridizing to the aptamer strand, Au NPs-linked hairpin DNA (Au-H
DNA1), and thiolated hairpin DNA (H-DNA2) previously immobilized on SPR gold
chip. In the absence of target, the H-DNA1 possessing hairpin structure cannot
hybridize with H-DNA2 and thereby Au NPs will not be captured on the SPR gold
chip surface. Upon addition of target, the detection probe c-DNA1 is forced to
dissociate from the c-DNA1/aptamer duplex by the specific recognition of the
target to its aptamer. The released c-DNA1 hybridizes with Au-H-DNA1 and opens
the hairpin structure, which accelerate the hybridization between Au-H-DNA1 and H
DNA2, leading to the displacement of the c-DNA1 through a branch migration
process. The released c-DNA1 then hybridizes with another Au-H-DNA1 probe, and
the cycle starts anew, resulting in the continuous immobilization of Au-H-DNA1
probes on the SPR chip, generating a significant change of SPR signal due to the
electronic coupling interaction between the localized surface plasma of the Au
NPs and the surface plasma wave. With the use of adenosine as a proof-of
principle analyte, this sensing platform can detect adenosine specifically with a
detection limit as low as 0.21 pM, providing a simple, sensitive and selective
protocol for small target molecules detection.
PMID- 25847159
TI - Platinum nanoparticles functionalized nitrogen doped graphene platform for
sensitive electrochemical glucose biosensing.
AB - In this work, we reported an efficient platinum nanoparticles functionalized
nitrogen doped graphene (PtNPs@NG) nanocomposite for devising novel
electrochemical glucose biosensor for the first time. The fabricated PtNPs@NG and
biosensor were characterized using transmission electron microscopy, high
resolution transmission electron microscopy, X-ray photoelectron spectroscopy,
static water contact angle, UV-vis spectroscopy, electrochemical impedance
spectra and cyclic voltammetry, respectively. PtNPs@NG showed large surface area
and excellent biocompatibility, and enhanced the direct electron transfer between
enzyme molecules and electrode surface. The glucose oxidase (GOx) immobilized on
PtNPs@NG nanocomposite retained its bioactivity, and exhibited a surface
controlled, quasi-reversible and fast electron transfer process. The constructed
glucose biosensor showed wide linear range from 0.005 to 1.1mM with high
sensitivity of 20.31 mA M(-1) cm(-2). The detection limit was calculated to be
0.002 mM at signal-to-noise of 3, which showed 20-fold decrease in comparison
with single NG-based electrochemical biosensor for glucose. The proposed glucose
biosensor also demonstrated excellent selectivity, good reproducibility,
acceptable stability, and could be successfully applied in the detection of
glucose in serum samples at the applied potential of -0.33 V. This research
provided a promising biosensing platform for the development of excellent
electrochemical biosensors.
PMID- 25847160
TI - A dual-responsive fluorescence method for the detection of clenbuterol based on
BSA-protected gold nanoclusters.
AB - The illegal feeding of clenbuterol (CLB) to domestic animals and the potential
harm of it to human health lead an urgent requirement for the efficient detection
of CLB, especially in the edible meat. In this paper we reported a new
fluorescence method for the detection of trace amount of CLB by using the BSA
protected gold nanoclusters (AuNCs@BSA). Under the excitation of either 280 or
500 nm the emission of AuNCs@BSA was quenched obviously by diazotized CLB,
supplying a dual-responsive fluorescence method to detect CLB in aqueous
solution. In addition, the linear response of the fluorescence intensity of
AuNCs@BSA to diazotized CLB allowed the quantitative detection of CLB in a range
of 4.0 nM-300 MUM upon excitation at two wavelength, and the limit of detection
for CLB was 3.0 nM upon 280 nm excitation and 1.6 nM upon 500 nm excitation,
respectively. In addition, the dual-responsive mechanism of AuNCs@BSA to CLB was
investigated in detail by using several CLB analogues and reference compounds.
Particularly, the proposed method was successfully applied to detect CLB in pork
mince and the results were validated well by HPLC, illustrating it could be used
as a reliable, rapid, and cost-effective technique for the determination of CLB
residues in real samples.
PMID- 25847161
TI - A highly selective molecularly imprinted electrochemiluminescence sensor for
ultra-trace beryllium detection.
AB - A new molecularly imprinted electrochemiluminescence (ECL) sensor was proposed
for highly sensitive and selective determination of ultratrace Be(2+)
determination. The complex of Be(2+) with 4-(2-pyridylazo)-resorcinol (PAR) was
chosen as the template molecule for the molecularly imprinted polymer (MIP). In
this assay, the complex molecule could be eluted from the MIP, and the cavities
formed could then selectively recognize the complex molecules. The cavities
formed could also work as the tunnel for the transfer of probe molecules to
produce sound responsive signal. The determination was based on the intensity of
the signal, which was proportional to the concentrations of the complex molecule
in the sample solution, and the Be(2+) concentration could then be determined
indirectly. The results showed that in the range of 7*10(-11 )mol L(-1) to
8.0*10(-9) mol L(-1), the ECL intensity had a linear relationship with the Be(2+)
concentrations, with the limit of detection of 2.35*10(-11) mol L(-1). This
method was successfully used to detect Be(2+) in real water samples.
PMID- 25847162
TI - Preparation and evaluation of poly(alkyl methacrylate-co-methacrylic acid-co
ethylene dimethacrylate) monolithic columns for separating polar small molecules
by capillary liquid chromatography.
AB - In this study, methacrylic acid (MAA) was incorporated with alkyl methacrylates
to increase the hydrophilicity of the synthesized ethylene dimethacrylate-based
(EDMA-based) monoliths for separating polar small molecules by capillary LC
analysis. Different alkyl methacrylate-MAA ratios were investigated to prepare a
series of 30% alkyl methacrylate-MAA-EDMA monoliths in fused-silica capillaries
(250-MUm i.d.). The porosity, permeability, and column efficiency of the
synthesized MAA-incorporated monolithic columns were characterized. A mixture of
phenol derivatives is employed to evaluate the applicability of using the
prepared monolithic columns for separating small molecules. Fast separation of
six phenol derivatives was achieved in 5 min with gradient elution using the
selected poly(lauryl methacrylate-co-MAA-co-EDMA) monolithic column. In addition,
the effect of acetonitrile content in mobile phase on retention factor and plate
height as well as the plate height-flow velocity curves were also investigated to
further examine the performance of the selected poly(lauryl methacrylate-co-MAA
co-EDMA) monolithic column. Moreover, the applicability of prepared polymer-based
monolithic column for potential food safety applications was also demonstrated by
analyzing five aflatoxins and three phenicol antibiotics using the selected
poly(lauryl methacrylate-co-MAA-co-EDMA) monolithic column.
PMID- 25847163
TI - Trilinearity deviation ratio: a new metric for chemometric analysis of
comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry
data.
AB - Comprehensive two-dimensional gas chromatography coupled with time-of-flight mass
spectrometry (GC*GC-TOFMS) is a well-established instrumental platform for
complex samples. However, chemometric data analysis is often required to fully
extract useful information from the data. We demonstrate that retention time
shifting from one modulation to the next, Delta(2)tR, is not sufficient alone to
quantitatively describe the trilinearity of a single GC*GC-TOFMS run for the
purpose of predicting the performance of the chemometric method parallel factor
analysis (PARAFAC). We hypothesize that analyte peak width on second dimension
separations, (2)Wb, also impacts trilinearity, along with Delta(2)tR. The term
trilinearity deviation ratio, TDR, which is Delta(2)tR normalized by (2)Wb, is
introduced as a quantitative metric to assess accuracy for PARAFAC of a GC*GC
TOFMS data cube. We explore how modulation ratio, MR, modulation period, PM,
temperature programming rate, Tramp, sampling phase (in-phase and out-of-phase),
and signal-to-noise ratio, S/N, all play a role in PARAFAC performance in the
context of TDR. Use of a PM in the 1-2 s range provides an optimized peak
capacity for the first dimension separation (500-600) for a 30 min run, with an
adequate peak capacity for the second dimension separation (12-15), concurrent
with an optimized two-dimensional peak capacity (6000-7500), combined with
sufficiently low TDR values (0-0.05) to facilitate low quantitative errors with
PARAFAC (0-0.5%). In contrast, use of a PM in the 5s or greater range provides a
higher peak capacity on the second dimension (30-35), concurrent with a lower
peak capacity on the first dimension (100-150) for a 30 min run, and a slightly
reduced two-dimensional peak capacity (3000-4500), and furthermore, the data are
not sufficiently trilinear for the more retained second dimension peaks in order
to directly use PARAFAC with confidence.
PMID- 25847164
TI - Size and concentration determination of (functionalised) fullerenes in surface
and sewage water matrices using field flow fractionation coupled to an online
accurate mass spectrometer: method development and validation.
AB - In order to assess the environmental risks of a compound it is imperative to have
suitable and reliable techniques for its determination in environmental matrices.
In this paper, we focused on a method development for the recently introduced
online coupling of a field flow fractionation (FFF) system to an Orbitrap-HRMS,
that allows the simultaneous size and concentration determination of different
aqueous fullerene aggregates and their concentrations in different size
fractions. A 0.05% NH4OH solution in water was identified as the best carrier
liquid for the analysis of the three different aqueous fullerene suspensions (C60
[60], [6,6]-phenyl-C61 butyric acid methyl ester ([60]PCBM) and [6,6]-(bis)phenyl
C61 butyric acid methyl ester ([60]bisPCBM)). The multi-angle light scattering
(MALS) data received after employing the ammonia solution was consistent with
both the theory and calibration using well defined Au and latex particles. The
LODs obtained using Orbitrap HRMS detection were 0.1 MUg L(-1) for an injection
volume of 100 MUL which are significantly better than the LODs obtained by using
UV (20 MUg L(-1)) and MALS detectors (5 MUg L(-1)). However, these LODs can be
further improved as in theory there is no limit to the amount of sample that can
be injected into the FFF. Environmental samples (river and sewage water) were
spiked with fullerenes and the fractograms obtained for these samples revealed
that the matrix does affect the size of fullerene aggregates. Information on the
size distribution can be useful for the risk assessment of these particles.
PMID- 25847165
TI - Fibre coupled micro-light emitting diode array light source with integrated band
pass filter for fluorescence detection in miniaturised analytical systems.
AB - In this work, a new type of miniaturized fibre-coupled solid-state light source
is demonstrated as an excitation source for fluorescence detection in capillary
electrophoresis. It is based on a parabolically shaped micro-light emitting diode
(MU-LED) array with a custom band-pass optical interference filter (IF) deposited
at the back of the LED substrate. The GaN MU-LED array consisted of 270
individual MU-LED elements with a peak emission at 470 nm, each about 14 MUm in
diameter and operated as a single unit. Light was extracted through the
transparent substrate material, and coupled to an optical fibre (OF, 400 MUm in
diameter, numerical aperture NA=0.37), to form an integrated MU-LED-IF-OF light
source component. This packaged MU-LED-IF-OF light source emitted approximately
225 MUW of optical power at a bias current of 20 mA. The bandpass IF filter was
designed to reduce undesirable LED light emissions in the wavelength range above
490 nm. Devices with and without IF were compared in terms of the optical power
output, spectral characteristics as well as LOD values. While the IF consisted of
only 7.5 pairs (15 layers) of SiO2/HfO2 layers, it resulted in an improvement of
the baseline noise as well as the detection limit measured using fluorescein as
test analyte, both by approximately one order of magnitude, with a LOD of 1*10(
8) mol L(-1) obtained under optimised conditions. The MU-LED-IF-OF light source
was then demonstrated for use in capillary electrophoresis with fluorimetric
detection. The limits of detection obtained by this device were compared to those
obtained with a commercial fibre coupled LED device.
PMID- 25847166
TI - Severe acute abdomen caused by symptomatic Meckel's diverticulum in three
children with trisomy 18.
AB - Meckel's diverticulum (MD) is the most prevalent congenital anomaly of the
gastrointestinal tract and often presents a diagnostic challenge. Patients with
trisomy 18 frequently have MD, but the poor prognosis and lack of consensus
regarding management for neonates has meant that precise information on the
clinical manifestations in infants and children with MD is lacking. We describe
the cases of three children with trisomy 18 who developed symptomatic MD.
Intussusception was diagnosed in Patient 1, intestinal volvulus in Patient 2, and
gastrointestinal bleeding in Patient 3. All three patients underwent surgical
treatment and only the Patient 1 died due to pulmonary hypertensive crisis. The
other two patients experienced no further episodes of abdominal symptoms. In
patients with trisomy 18, although consideration of postoperative complications
and prognosis after surgical treatment is necessary, symptomatic MD should carry
a high index of suspicion in patients presenting with acute abdomen.
PMID- 25847168
TI - Complex Adaptive Systems, soil degradation and land sensitivity to
desertification: A multivariate assessment of Italian agro-forest landscape.
AB - Degradation of soils and sensitivity of land to desertification are intensified
in last decades in the Mediterranean region producing heterogeneous spatial
patterns determined by the interplay of factors such as climate, land-use
changes, and human pressure. The present study hypothesizes that rising levels of
soil degradation and land sensitivity to desertification are reflected into
increasingly complex (and non-linear) relationships between environmental and
socioeconomic variables. To verify this hypothesis, the Complex Adaptive Systems
(CAS) framework was used to explore the spatiotemporal dynamics of eleven
indicators derived from a standard assessment of soil degradation and land
sensitivity to desertification in Italy. Indicators were made available on a
detailed spatial scale (773 agricultural districts) for various years (1960,
1990, 2000 and 2010) and analyzed through a multi-dimensional exploratory data
analysis. Our results indicate that the number of significant pair-wise
correlations observed between indicators increased with the level of soil and
land degradation, although with marked differences between northern and southern
Italy. 'Fast' and 'slow' factors underlying soil and land degradation, and
'rapidly-evolving' or 'locked' agricultural districts were identified according
to the rapidity of change estimated for each of the indicators studied. In
southern Italy, 'rapidly-evolving' districts show a high level of soil
degradation and land sensitivity to desertification during the whole period of
investigation. On the contrary, those districts in northern Italy are those
experiencing a moderate soil degradation and land sensitivity to desertification
with the highest increase in the level of sensitivity over time. The study
framework contributes to the assessment of complex local systems' dynamics in
affluent but divided countries. Results may inform thematic strategies for the
mitigation of land and soil degradation in the framework of action plans to
combat desertification.
PMID- 25847167
TI - Trihalomethane exposure and biomonitoring for the liver injury indicator, alanine
aminotransferase, in the United States population (NHANES 1999-2006).
AB - Exposure to trihalomethanes (or THMs: chloroform, bromoform,
bromodichloromethane, and dibromochloromethane [DBCM]) formed via drinking water
disinfection has been associated with adverse reproductive outcomes and cancers
of the digestive or genitourinary organs. However, few studies have examined
potential associations between THMs and liver injury in humans, even though
experimental studies suggest that these agents exert hepatotoxic effects,
particularly among obese individuals. This study examined participants in the
National Health and Nutrition Examination Survey (1999-2006, N=2781) to test the
hypothesis that THMs are associated with liver injury as assessed by alanine
aminotransferase (ALT) activity in circulation. Effect modification by body mass
index (BMI) or alcohol consumption also was examined. Associations between blood
THM concentrations and ALT activity were assessed using unconditional multiple
logistic regression to calculate prevalence odds ratios (ORs) with 95% confidence
intervals (CIs) for exposure among cases with elevated ALT activity (men:
>40IU/L, women: >30IU/L) relative to those with normal ALT, after adjustment for
variables that may confound the relationship between ALT and THMs. Compared to
controls, cases were 1.35 times more likely (95% CI: 1.02, 1.79) to have
circulating DBCM concentrations exceeding median values in the study population.
There was little evidence for effect modification by BMI, although the
association varied by alcohol consumption. Among non-drinkers, cases were more
likely than controls to be exposed to DBCM (OR: 3.30, 95% CI: 1.37, 7.90),
bromoform (OR: 2.88, 95% CI: 1.21, 6.81), or brominated THMs (OR: 4.00, 95% CI:
1.31, 12.1), but no association was observed among participants with low, or
moderate to heavy alcohol consumption. Total THM levels exceeding benchmark
exposure limits continue to be reported both in the United States and globally.
Results from this study suggest a need for further characterization of ALT
activity and possibly other hepatic or metabolic diseases in populations with
elevated drinking water THM concentrations.
PMID- 25847169
TI - Selenium contaminated waters: An overview of analytical methods, treatment
options and recent advances in sorption methods.
AB - Selenium is an essential trace element for many organisms, including humans, but
it is bioaccumulative and toxic at higher than homeostatic levels. Both selenium
deficiency and toxicity are problems around the world. Mines, coal-fired power
plants, oil refineries and agriculture are important examples of anthropogenic
sources, generating contaminated waters and wastewaters. For reasons of human
health and ecotoxicity, selenium concentration has to be controlled in drinking
water and in wastewater, as it is a potential pollutant of water bodies. This
review article provides firstly a general overview about selenium distribution,
sources, chemistry, toxicity and environmental impact. Analytical techniques used
for Se determination and speciation and water and wastewater treatment options
are reviewed. In particular, published works on adsorption as a treatment method
for Se removal from aqueous solutions are critically analyzed. Recent published
literature has given particular attention to the development and search for
effective adsorbents, including low-cost alternative materials. Published works
mostly consist in exploratory findings and laboratory-scale experiments. Binary
metal oxides and LDHs (layered double hydroxides) have presented excellent
adsorption capacities for selenium species. Unconventional sorbents (algae,
agricultural wastes and other biomaterials), in raw or modified forms, have also
led to very interesting results with the advantage of their availability and low
cost. Some directions to be considered in future works are also suggested.
PMID- 25847170
TI - Growth and (137)Cs uptake of four Brassica species influenced by inoculation with
a plant growth-promoting rhizobacterium Bacillus pumilus in three contaminated
farmlands in Fukushima prefecture, Japan.
AB - The effectiveness of the plant growth-promoting rhizobacterium Bacillus pumilus
regarding growth promotion and radiocesium ((137)Cs) uptake was evaluated in four
Brassica species grown on different (137)Cs contaminated farmlands at Fukushima
prefecture in Japan from June to August 2012. B. pumilus inoculation did not
enhance growth in any of the plants, although it resulted in a significant
increase of (137)Cs concentration and higher (137)Cs transfer from the soil to
plants. The Brassica species exhibited different (137)Cs uptake abilities in the
order Komatsuna>turnip>mustard>radish. TF values of (137)Cs ranged from 0.018 to
0.069 for all vegetables. Komatsuna possessed the largest root surface area and
root volume, and showed a higher (137)Cs concentration in plant tissue and higher
(137)Cs TF values (0.060) than the other vegetables. Higher (137)Cs transfer to
plants was prominent in soil with a high amount of organic matter and an Al
vermiculite clay mineral type.
PMID- 25847171
TI - Remediating radium contaminated legacy sites: Advances made through machine
learning in routine monitoring of "hot" particles.
AB - The extensive use of radium during the 20th century for industrial, military and
pharmaceutical purposes has led to a large number of contaminated legacy sites
across Europe and North America. Sites that pose a high risk to the general
public can present expensive and long-term remediation projects. Often the most
pragmatic remediation approach is through routine monitoring operating gamma-ray
detectors to identify, in real-time, the signal from the most hazardous
heterogeneous contamination (hot particles); thus facilitating their removal and
safe disposal. However, current detection systems do not fully utilise all
spectral information resulting in low detection rates and ultimately an increased
risk to the human health. The aim of this study was to establish an optimised
detector-algorithm combination. To achieve this, field data was collected using
two handheld detectors (sodium iodide and lanthanum bromide) and a number of
Monte Carlo simulated hot particles were randomly injected into the field data.
This allowed for the detection rate of conventional deterministic (gross counts)
and machine learning (neural networks and support vector machines) algorithms to
be assessed. The results demonstrated that a Neural Network operated on a sodium
iodide detector provided the best detection capability. Compared to deterministic
approaches, this optimised detection system could detect a hot particle on
average 10cm deeper into the soil column or with half of the activity at the same
depth. It was also found that noise presented by internal contamination
restricted lanthanum bromide for this application.
PMID- 25847172
TI - Climate-driven terrestrial inputs in ultraoligotrophic mountain streams of Andean
Patagonia revealed through chromophoric and fluorescent dissolved organic matter.
AB - Fluvial networks transport a substantial fraction of the terrestrial production,
contributing to the global carbon cycle and being shaped by hydrologic, natural
and anthropogenic factors. In this investigation, four Andean Patagonian
oligotrophic streams connecting a forested catchment (~125km(2)) and draining to
a double-basin large and deep lake (Lake Moreno complex, Northwestern Patagonia),
were surveyed to analyze the dynamics of the allochthonous subsidy. The results
of a 30month survey showed that the catchment supplies nutrients and dissolved
organic matter (DOM) to the streams. The eruption of the Puyehue-Cordon Caulle at
the beginning of the study overlapped with seasonal precipitation events. The
largest terrestrial input was timed with precipitation which increased
particulate materials, nutrients and DOM through enhanced runoff. Baseline
suspended solids and nutrients were very low in all the streams (suspended
solids: ~1mg/L; total nitrogen: ~0.02mg/L; total phosphorus: ~5MUg/L), increasing
several fold with runoff. Baseline dissolved organic carbon concentrations (DOC)
ranged between 0.15 and 1mg/L peaking up to three-fold. Chromophoric and
fluorescent analyses characterized the DOM as of large molecular weight and high
aromaticity. Parallel factor modeling (PARAFAC) of DOM fluorescence matrices
revealed three components of terrestrial origin, with certain degree of microbial
processing: C1 and C2 (terrestrial humic-like compounds) and C3 (protein-like and
pigment derived compounds). Seasonal changes in MOD quality represent different
breakdown stages of the allochthonous DOM. Our survey allowed us to record and
discuss the effects of the Puyehue-Cordon Caulle eruption, showing that due to
the high slopes, high current and discharge of the streams the volcanic material
was rapidly exported to the Moreno Lake complex. Overall, this survey underscores
the magnitude and timing of the allochthonous input revealing the terrestrial
subsidy to food webs in Patagonian freshwaters, which are among the most
oligotrophic systems of the world.
PMID- 25847173
TI - Trihalomethane formation potential of aquatic and terrestrial fulvic and humic
acids: Sorption on activated carbon.
AB - Humic substances (HSs) are precursors for the formation of hazardous disinfection
by-products (DBPs) during chlorination of water. Various surrogate parameters
have been used to investigate the generation of DBPs by HS precursors and the
removal of these precursors by activated carbon treatment. Dissolved organic
carbon (DOC)- and ultraviolet absorbance (UVA254)-based isotherms are commonly
reported and presumed to be good predictors of the trihalomethane formation
potential (THMFP). However, THMFP-based isotherms are rarely published such that
the three types of parameters have not been compared directly. Batch equilibrium
experiments on activated carbon were used to generate constant-initial
concentration sorption isotherms for well-characterized samples obtained from the
International Humic Substances Society (IHSS). HSs representing type (fulvic acid
[FA], humic acid [HA]), origin (aquatic, terrestrial), and geographical source
(Nordic, Suwannee, Peat, Soil) were examined at pH6 and pH9. THMFP-based
isotherms were generated and compared to determine if DOC- and UVA254-based
isotherms were good predictors of the THMFP. The sorption process depended on the
composition of the HSs and the chemical nature of the activated carbon, both of
which were influenced by pH. Activated carbon removal of THM-precursors was pH-
and HS-dependent. In some instances, the THMFP existed after UVA254 was depleted.
PMID- 25847174
TI - Antifungal properties of silver nanoparticles against indoor mould growth.
AB - The presence of moulds in indoor environments causes serious diseases and acute
or chronic toxicological syndromes. In order to inhibit or prevent the growth of
microorganisms on building materials, the disruption of their vital processes or
the reduction of reproduction is required. The development of novel techniques
that impair the growth of microorganisms on building materials is usually based
on silver nanoparticles (AgNPs). It makes them an alternative to other biocides.
AgNPs have proven antibacterial activity and became promising in relation to
fungi. The aim of the study was to assess growth and morphology of mycelia of
typical indoor fungal species: Penicillium brevicompactum, Aspergillus fumigatus,
Cladosporium cladosporoides, Chaetomium globosum and Stachybotrys chartarum as
well as Mortierella alpina, cultured on agar media. The antifungal activity of
AgNPs was also tested in relation to C. globosum and S. chartarum grown on the
surface of gypsum drywall. It was found that the presence of AgNPs in
concentrations of 30-200mg/l significantly decreased the growth of fungi.
However, in the case of M. alpina, AgNPs stimulated its growth. Moreover, strong
changes in moulds morphology and colour were observed after administration of
AgNPs. Parameters of conidiophores/sporangiophores varied depending on mould
region and changed significantly after treatment with AgNPs. The experiments have
shown antifungal properties of AgNPs against common indoor mould species. Their
application to building materials could effectively protect indoor environments
from mould development. However, consideration must be given to the fact that the
growth of some fungal strains might be stimulated by AgNPs.
PMID- 25847175
TI - Quantification of potential exposure of gray partridge (Perdix perdix) to
pesticide active substances in farmlands.
AB - Estimating exposure of wild birds to plant protection products is of key
importance in the risk assessment process evaluating their harmful potential. In
this paper, we propose an ecologically-relevant methodology to estimate potential
exposure to active substances (ASs) of a farmland focal bird, the gray partridge
Perdix perdix. It is based on bird habitat use of fields at the time of pesticide
applications. It accounts for spatio-temporal heterogeneity at population and
landscape scales. We identify and quantify the potential exposure to 179 ASs of
140 clutches during pre-laying, laying, and incubation phases, and of 75 coveys.
The data come from a large scale field study combining radiotelemetry and a
farmer survey. They were collected in 12 different representative sites. The
proportion of clutches potentially exposed to a given chemical was >=5% for 32
ASs; prothioconazole and epoxiconazole ranking first. 71% of clutches were
potentially exposed to >=1 AS and 67% to >=2 ASs. Mixtures involved 2 to 22 ASs.
They emerged from commercial formulations, tank mixtures, bird habitat use, and
combinations. ASs were fungicides (53%), herbicides (25%), and insecticides (16%)
used on a variety of crops in April-June, when ground-nesting birds are breeding.
The European Food Safety Authority conclusions report a long-term first-tier
toxicity-to-exposure ratio (TERlt) <5 for 11 out of 19 documented ASs, and higher
tier TERlt <5 for 5 out of 10 ASs. This suggests a potential risk for bird
reproduction in farmlands. Globally 13% of coveys were potentially exposed to 18
ASs during the first month (1-4 coveys per AS). The use of our field data in
future research and risk assessment is discussed.
PMID- 25847176
TI - The geochemical transformation of soils by agriculture and its dependence on soil
erosion: An application of the geochemical mass balance approach.
AB - Agricultural activities alter elemental budgets of soils and thus their long-term
geochemical development and suitability for food production. This study examined
the utility of a geochemical mass balance approach that has been frequently used
for understanding geochemical aspect of soil formation, but has not previously
been applied to agricultural settings. Protected forest served as a reference to
quantify the cumulative fluxes of Ca, P, K, and Pb at a nearby tilled crop land.
This comparison was made at two sites with contrasting erosional environments:
relatively flat Coastal Plain in Delaware vs. hilly Piedmont in Pennsylvania.
Mass balance calculations suggested that liming not only replenished the Ca lost
prior to agricultural practice but also added substantial surplus at both sites.
At the relatively slowly eroding Coastal Plain site, the agricultural soil
exhibited enrichment of P and less depletion of K, while both elements were
depleted in the forest soil. At the rapidly eroding Piedmont site, erosion
inhibited P enrichment. In similar, agricultural Pb contamination appeared to
have resulted in Pb enrichment in the relatively slowly eroding Coastal Plain
agricultural soil, while not in the rapidly eroding Piedmont soils. We conclude
that agricultural practices transform soils into a new geochemical state where
current levels of Ca, P, and Pb exceed those provided by the local soil minerals,
but such impacts are significantly offset by soil erosion.
PMID- 25847177
TI - Small intestinal lactoferrin and calprotectin levels in different stages of
necrotizing enterocolitis in a rat model.
AB - PURPOSE: Necrotizing enterocolitis (NEC) is a severe disease of mostly premature
infants with high morbidity and mortality rates. There is no reliable biomarker
for detecting newborns at risk for NEC development. We aimed to investigate small
intestinal lactoferrin (LF) and calprotectin (CAL) levels as predictors and
indicators of disease severity in an experimental newborn rat model. MATERIALS
AND METHODS: Newborn pups were randomly divided into two groups, NEC and control.
The NEC group pups were decapitated on the second, third and fourth days of the
experiment for an assessment of the different stages of NEC. In the study group,
hypoxia-reoxygenation model used to induce NEC. As biochemical parameters, small
intestinal LF and CAL levels were measured with an enzyme-linked immunosorbent
assay technique and intestinal injury scoring was evaluated as a pathologic
parameter. RESULTS: Small intestinal levels of both LF and CAL increased in the
second and the third day groups, but began to decrease by the fourth day. The
first, second and third day levels of LF and CAL were higher than controls. The
intestinal injury scores of all NEC groups were significantly higher than the
control group. CONCLUSION: Small intestinal lactoferrin and calprotectin were
good markers for demonstrating NEC. However, instead of spot testing, monitoring
the levels of these markers may be more informative.
PMID- 25847178
TI - D-dimer for risk stratification in haemodynamically stable patients with acute
pulmonary embolism.
AB - PURPOSE: Patients with submassive pulmonary embolism (PE) have a higher short
term mortality than those with low-risk PE. Rapid identification of submassive PE
is important for adequate treatment of non-massive PE. We aimed to investigate
the utility of D-dimer for the prediction of submassive PE stadium in
normotensive PE patients. PATIENTS AND METHODS: Normotensive PE patients were
classified into submassive or low-risk PE groups. In addition to the comparison
of the groups, area under the curve (AUC) and D-dimer cut-off for the prediction
of submassive PE stadium, multi-variate logistic regression for association
between D-dimer values above this cut-off and submassive PE stadium were also
calculated. RESULTS: The data of 129 normotensive PE patients (59.7% women, mean
age 70.0 years (60.7/81.0)) were analysed retrospectively. Patients with
submassive PE were older (75.0 years (61.7/81.0) vs. 66.5 years (55.7/74.2),
P=0.026) and more frequently female (63.6% vs. 53.8%, P=0.35). Heart rate
(100.0beats/min (85.0/108.0) vs. 80.0beats/min (70.0/96.2), P<0.0001), systolic
pulmonary-artery pressure (41.55+/-16.79mmHg vs. 22.62+/-14.81mmHg, P<0.0001),
and D-dimer (2.00mg/l (1.09/3.98) vs. 1.21mg/l (0.75/1.99), P=0.011) were higher
in patients with submassive PE. D-dimer values >1.32mg/l were indicative of
submassive PE and shock-index >=0.7. The effectiveness (AUC) of the test was 0.63
for submassive PE and 0.64 for shock-index >=0.7. D-dimer values >1.32mg/l were
associated with submassive PE stadium (OR 3.81 (95% CI: 1.74-8.35), P=0.00083) as
well as with systolic blood pressure (OR 0.98 (95% CI: 0.97-0.99), P=0.033),
heart rate (OR 1.02 (95% CI: 1.00-1.04), P=0.023) and shock-index value (OR 15.89
(95% CI: 1.94-130.08), P=0.0099). CONCLUSIONS: D-dimer values >1.32mg/l are
indicative of submassive PE stadium and shock-index >=0.7. Efficacy of D-dimer
for predicting submassive PE stadium was only weak to moderate.
PMID- 25847179
TI - Dysfunctional prefrontal gamma-band oscillations reflect working memory and other
cognitive deficits in schizophrenia.
AB - Impairments in working memory (WM) and other cognitive functions are cardinal
neuropsychological symptoms in schizophrenia (ScZ). The prefrontal cortex (PFC)
is important for mediating and executing these functions. Functional neuroimaging
and molecular studies have consistently shown PFC abnormalities in ScZ. In
addition, recent studies have suggested that impairments in oscillatory activity,
especially in the gamma band (approximately 30-80 Hz), reflect disturbed cortical
information processing in this patient group. Here we review evidence that
dysfunctional gamma-band responses (GBR) in the PFC could be a factor
contributing to WM and other cognitive deficits in ScZ. We provide an overview of
noninvasive electrophysiological studies reporting frontal GBR abnormalities in
ScZ patients during WM and other cognitive tasks. In agreement with the often
reported hypofrontality in functional neuroimaging studies, the majority of
reviewed studies revealed reduced amplitudes or reduced phase locking of GBR over
frontal areas in this patient group. Clinical implications derived from these
findings and possibilities to foster future studies on GBR abnormalities in ScZ
patients, are discussed. Since oscillatory activity in the gamma band has
previously been linked to a variety of neurotransmitters, such as the gamma
aminobutyric acid-ergic system, the study of prefrontal GBR could also have
implications for pharmacologic approaches in the treatment of WM and other
cognitive deficits in ScZ.
PMID- 25847181
TI - Parents' and children's acceptance of skim chocolate milks sweetened by monk
fruit and stevia leaf extracts.
AB - Chocolate milk increases milk consumption of children, but high sugar content
raises health concerns. Interest in sugar reduction and parents' preference for
natural sweeteners necessitates further research on natural nonnutritive
sweeteners. However, it is important to maintain consumer acceptability,
especially for children, while reducing sugar in chocolate milk. The objectives
of this study were to identify the sweetness intensity perception of stevia leaf
(STV) and monk fruit (MK) extracts in skim chocolate milk (SCM), to evaluate STV
and MK as the sole or partial sweetener source for SCM for young adults (19 to 35
y) and children (5 to 13 y), and to determine if information on natural
nonnutritive sweeteners impacted parents' acceptability of SCM. Power function
and 2-alternative forced choice studies were used to determine the iso-sweetness
of nonnutritive sweeteners to a sucrose control in SCM (51.4 g/L, SUC control).
Young adults (n = 131) evaluated 9 different SCM (SUC control, STV, MK,
STV:sucrose blends, or MK:sucrose blends) in a completely randomized 2-d test.
Children (n = 167) evaluated SUC control SCM and SCM with 39.7 g/L sucrose and 46
mg/L MK (MK25) or 30 mg/L STV (STV25). Parents evaluated SUC control, MK25, and
STV25 in a balanced crossover design with a 40-d wait time between primed or
unprimed ballots. Chocolate milks solely sweetened by nonnutritive sweeteners
were less acceptable compared with SUC control by young adults. MK25 and STV25
were acceptable by young adults and children. The presentation of chocolate milk
label information had different effects on parental acceptance. Traditional
parents preferred sucrose sweetened SCM, and label conscious parents preferred
SCM with natural nonnutritive sweeteners.
PMID- 25847182
TI - Improving Milk Intake in Milk-Averse Lactose Digesters and Maldigesters.
AB - OBJECTIVE: To determine whether a 21-day milk-drinking intervention could reverse
milk aversion. DESIGN: Participants consumed increasing amounts of cow's milk for
21 days. Milk and dairy consumption, aversion, and likeness were assessed pre-
and post-intervention and at 3 and 6 months post-intervention. SETTING: A large
Midwestern university. PARTICIPANTS: Twenty-seven milk-averse individuals
completed the intervention, 26 completed the 3-month follow-up, and 24 completed
the 6-month follow-up. MAIN OUTCOMES MEASURED: Participants self-reported milk
and dairy consumption, aversion, and degree to which they liked milk. ANALYSIS:
Analysis of variance determined between-subject effects. Independent samples t
test determined the effect of time. Fisher exact test determined factors
affecting milk consumption. RESULTS: Lactose digesters and maldigesters showed a
significant decrease in overall symptom scores after the milk intervention, with
no significant difference between groups. Independent of digestive status,
subjects demonstrated a significant decrease in aversion, an increase in the
amount to which they liked milk, and an increase in milk and overall calcium
consumption at 3 and 6 months post-intervention. CONCLUSIONS AND IMPLICATIONS:
The results suggest a reversal of milk avoidance and the possibility that milk
avoiders can increase likeness and incorporate milk into their diet after
exposure.
PMID- 25847180
TI - In search of multimodal neuroimaging biomarkers of cognitive deficits in
schizophrenia.
AB - BACKGROUND: The cognitive deficits of schizophrenia are largely resistant to
current treatments and thus are a lifelong illness burden. The Measurement and
Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus
Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition
across major cognitive domains; however, the multimodal brain alterations
specifically associated with MCCB in schizophrenia have not been examined.
METHODS: The interrelationships between MCCB and the abnormalities seen in three
types of neuroimaging-derived maps-fractional amplitude of low-frequency
fluctuations (fALFF) from resting-state functional magnetic resonance imaging
(MRI), gray matter (GM) density from structural MRI, and fractional anisotropy
from diffusion MRI-were investigated by using multiset canonical correlation
analysis in data from 47 schizophrenia patients treated with antipsychotic
medications and 50 age-matched healthy control subjects. RESULTS: One multimodal
component (canonical variant 8) was identified as both group differentiating and
significantly correlated with the MCCB composite. It demonstrated 1) increased
cognitive performance associated with higher fALFF (intensity of regional
spontaneous brain activity) and higher GM volumes in thalamus, striatum,
hippocampus, and the mid-occipital region, with co-occurring fractional
anisotropy changes in superior longitudinal fascicules, anterior thalamic
radiation, and forceps major; 2) higher fALFF but lower GM volume in dorsolateral
prefrontal cortex related to worse cognition in schizophrenia; and 3) distinct
domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased
fALFF in inferior parietal lobule particularly correlated with decreased social
cognition. Medication dose did not relate to these findings in schizophrenia.
CONCLUSIONS: Our results suggest linked functional and structural deficits in
distributed cortico-striato-thalamic circuits may be closely related to MCCB
measured cognitive impairments in schizophrenia.
PMID- 25847184
TI - Evaluation of Tc-99 m Labeled Dimeric GX1 Peptides for Imaging of Colorectal
Cancer Vasculature.
AB - PURPOSE: This study aimed to evaluate the potential of PEGylated dimeric GX1
peptide as a radiotracer for imaging of colorectal cancer vasculature in a LoVo
tumor xenografted mouse model. PROCEDURES: The [(99m)Tc]PEG-(GX1)2 peptide was
synthesized and identified. Confocal immunofluorescence analysis, receptor
binding assay, and competitive inhibition assay were performed to evaluate the
binding specificity and the receptor binding affinity of PEG-(GX1)2 to Co-human
umbilical vein endothelial cells (HUVECs). Single photon emission computed
tomography imaging and biodistribution were performed to evaluate the targeting
ability of PEG-(GX1)2 to colorectal cancer. RESULTS: The studies in vitro
suggested that PEG-(GX1)2 co-localized with Factor VIII in the perinuclear
cytoplasm of Co-HUVECs and bound specifically to Co-HUVECs with a high affinity.
The studies in vivo demonstrated that the targeting efficacy of PEG-(GX1)2 was
superior to GX1. CONCLUSIONS: PEGylation improved the affinity and the targeting
ability of the GX1 peptide. PEG-(GX1)2 is a more promising probe for imaging of
colorectal vasculature than GX1.
PMID- 25847185
TI - Validation of a predictive model for the growth of chalk yeasts on bread.
AB - The present study focused on the effects of temperature, T, and water activity,
aw, on the growth of Hyphopichia burtonii, Pichia anomala, and Saccharomycopsis
fibuligera on Sabouraud Agar Medium. Cardinal values were estimated by means of
cardinal models with inflection. All the yeasts were xerophilic, and they
exhibited growth at 0.85 aw. The combined effects of T, aw, and pH on the growth
of these species were described by the gamma-concept and validated on bread in
the range of 15-25 degrees C, 0.91-0.97 aw, and pH 4.6-6.8. The optimum growth
rates on bread were 2.88, 0.259, and 1.06 mm/day for H. burtonii, P. anomala, and
S. fibuligera, respectively. The optimal growth rate of S. fibuligera on bread
was about 2 fold that obtained on Sabouraud. Due to reproduction by budding, P.
anomala exhibited low growth on Sabouraud and bread. However, this species is of
major concern in the baker's industry because of the production of ethyl acetate
in bread.
PMID- 25847183
TI - Development and validation of panoptic Meso scale discovery assay to quantify
total systemic interleukin-6.
AB - AIM: Interleukin-6 (IL-6), a multifunctional cytokine, exists in several forms
ranging from a low molecular weight (MW 20-30 kDa) non-complexed form to high MW
(200-450 kDa), complexes. Accurate baseline IL-6 assessment is pivotal to
understand clinical responses to IL-6-targeted treatments. Existing assays
measure only the low MW, non-complexed IL-6 form. The present work aimed to
develop a validated assay to measure accurately total IL-6 (complexed and non
complexed) in serum or plasma as matrix in a high throughput and easily
standardized format for clinical testing. METHODS: Commercial capture and
detection antibodies were screened against humanized IL-6 and evaluated in an
enzyme-linked immunosorbent assay format. The best antibody combinations were
screened to identify an antibody pair that gave minimum background and maximum
recovery of IL-6 in the presence of 100% serum matrix. A plate-based total IL-6
assay was developed and transferred to the Meso Scale Discovery (MSD) platform
for large scale clinical testing. RESULTS: The top-performing antibody pair from
36 capture and four detection candidates was validated on the MSD platform. The
lower limit of quantification in human serum samples (n = 6) was 9.77 pg l(-1) ,
recovery ranged from 93.13-113.27%, the overall pooled coefficients of variation
were 20.12% (inter-assay) and 8.67% (intra-assay). High MW forms of IL-6, in size
fractionated serum samples from myelodysplastic syndrome and rheumatoid arthritis
patients, were detected by the assay but not by a commercial kit. CONCLUSION:
This novel panoptic (sees all forms) IL-6 MSD assay that measures both high and
low MW forms may have clinical utility.
PMID- 25847186
TI - Stochastic modelling of Listeria monocytogenes single cell growth in cottage
cheese with mesophilic lactic acid bacteria from aroma producing cultures.
AB - A stochastic model was developed for simultaneous growth of low numbers of
Listeria monocytogenes and populations of lactic acid bacteria from the aroma
producing cultures applied in cottage cheese. During more than two years,
different batches of cottage cheese with aroma culture were analysed for pH,
lactic acid concentration and initial concentration of lactic acid bacteria.
These data and bootstrap sampling were used to represent product variability in
the stochastic model. Lag time data were estimated from observed growth data
(lactic acid bacteria) and from literature on L. monocytogenes single cells.
These lag time data were expressed as relative lag times and included in growth
models. A stochastic model was developed from an existing deterministic growth
model including the effect of five environmental factors and inter-bacterial
interaction [Ostergaard, N.B, Eklow, A and Dalgaard, P. 2014. Modelling the
effect of lactic acid bacteria from starter- and aroma culture on growth of
Listeria monocytogenes in cottage cheese. International Journal of Food
Microbiology. 188, 15-25]. Growth of L. monocytogenes single cells, using lag
time distributions corresponding to three different stress levels, was simulated.
The simulated growth was subsequently compared to growth of low concentrations
(0.4-1.0 CFU/g) of L. monocytogenes in cottage cheese, exposed to similar
stresses, and in general a good agreement was observed. In addition, growth
simulations were performed using population relative lag time distributions for
L. monocytogenes as reported in literature. Comparably good predictions were
obtained as for the simulations performed using lag time data for individual
cells of L. monocytogenes. Therefore, when lag time data for individual cells are
not available, it was suggested that relative lag time distributions for L.
monocytogenes can be used as a qualified default assumption when simulating
growth of low concentrations of L. monocytogenes.
PMID- 25847187
TI - Validity and reliability of the Chinese version of the Sheehan Disability Scale
(SDS-C).
AB - INTRODUCTIONS: This study aims to evaluate the validity and reliability of the
Chinese version of the Sheehan Disability Scale (SDS-C) among depression patients
in Taiwan. METHODS: To validate the SDS-C, two samples were selected: Sample 1 (n
= 78) consisted of patients diagnosed with Depressive Disorder, while sample 2 (n
= 63) consisted of a nondepressive population. Sample 1 was evaluated with SDS
twice with 7-14 days interval to measure test-retest reliability. Both samples
were also evaluated with The Centre for Epidemiologic Studies Depression Scale
(CESD), Family APGAR (adaptation, partnership, growth, affection, resolve) score,
the Global Assessment of Functioning (GAF), and brief questionnaire of the World
Health Organization Quality of Life instrument (WHOQOL-BREF) and by a
psychiatrist. The two samples were combined to measure validity. RESULTS: In
concurrent validity, SDS-C scores were significantly correlated with the total
score of GAF. The discriminative validity was carried out by comparing the score
of SDS-C between subjects with and without current depressive disorder (t =
12.32, df = 139, P < 0.001). Another discriminative validity by receiver
operating characteristic analysis showed the optimal cut-point was >11
(sensitivity: 82.1, specificity: 93.7). The area under the curve was 0.93 (+/
0.02). For the factor validity, principal components analysis showed that a
single factor solution was the best solution accounting for 88.9% of the
variance. Regarding the construct validity, SDS-C scores were significantly
correlated with CESD, WHOQOL-BREF, and the Family APGAR score. For test-retest
reliability, the intra-class correlation coefficient for the total SDS-C score
was 0.89 (95% confidence interval 0.82-0.93) and internal consistency Cronbach's
alpha was 0.94. DISCUSSION: The SDS-C was found to be a valid and reliable
instrument for current depressive disorder patients in Taiwan.
PMID- 25847188
TI - Employment in Adults with Down Syndrome in the United States: Results from a
National Survey.
AB - BACKGROUND: There is no current data about employment/unemployment of adults with
Down syndrome in the United States. The data that exists includes adults with
Down syndrome as part of the larger group of people with disabilities or people
with intellectual disability. METHOD: This study used a survey to investigate
paid and volunteer employment, unemployment, types of jobs, job training, job
settings, job schedules and job satisfaction in adults with Down syndrome. There
were 511 survey responses received. RESULTS: Findings were that there is high
unemployment for adults with Down syndrome and that current employment is in a
limited number of fields, primarily in the areas of food, janitorial work,
landscaping, and office work. A small percentage of respondents have full time
paid employment. A combination of part time paid employment and unpaid volunteer
work is typical. CONCLUSIONS: Implications for educators, counselors, legislators
and employers are discussed.
PMID- 25847189
TI - Predictors of 49-month mortality in Chinese nonagenarians and centenarians in
PLAD study.
AB - OBJECTIVE: To examine whether a set of well-known predictors of mortality in
younger elderly also maintain their importance in Chinese oldest old group.
DESIGN: A cross-sectional study of 1401 inhabitants aged 90 and older were
conducted in the area of Dujiangyan, China. 825 subjects participated and were
followed up for vital status after 49 months. Professional interviewers collected
baseline data concerning socio-demographic characteristics, lifestyle habits,
physical factors and geriatric assessment. Bivariate analysis was conducted
between survivors and deceased. Cox regression models were used to evaluate
predictors of mortality. RESULTS: Four hundred and thirty-six (52.8%) of 825
participants eligible for the analysis died during the 49 months of follow-up
period. Older age, comorbidity, lower MMSE score, lower ADL and IADL scores
increased the risk of mortality in the study group. Multivariate analyses showed
older age (HR = 1.03, 95% CI 1.01-1.07) and comorbidity (HR = 1.09, 95% CI 1.02
1.17) were associated with mortality while female gender (HR = 0.61, 95% CI 0.43
0.86), taking exercise (HR = 0.80, 95% CI 0.64-1.01) and higher MMSE scores (HR =
0.96, 95% CI 0.94-0.99) showed a positive effect on survival. CONCLUSION: In
Chinese nonagenarians and centenarians, age, gender, taking exercise, cognitive
impairment and comorbidity at baseline show predictive power of oldest old
mortality.
PMID- 25847192
TI - The effect of chlorine and fluorine substitutions on tuning the ionization
potential of benzoate-bridged paddlewheel diruthenium(ii, ii) complexes.
AB - A series of paddlewheel diruthenium(ii, ii) complexes with various chlorine
substituted benzoate ligands (Cl-series) was synthesized as tetrahydrofuran (THF)
adducts [Ru2(ClxPhCO2)4(THF)2]; where ClxPhCO2(-) = o-chlorobenzoate, ; m
chlorobenzoate, ; p-chlorobenzoate, ; 2,3-dichlorobenzoate, ; 2,4
dichlorobenzoate, ; 2,5-dichlorobenzoate, ; 2,6-dichlorobenzoate, ; 3,4
dichlorobenzoate, ; 3,5-dichlorobenzoate, ; 2,3,4-trichlorobenzoate, ; 2,3,5
trichlorobenzoate, ; 2,4,5-trichlorobenzoate, ; 3,4,5-trichlorobenzoate, ;
2,3,4,5-tetrachlorobenzoate, . This Cl-series and the previously synthesized F
series together with four new fluorine-substituted derivatives,
[Ru2(FxPhCO2)4(THF)2] (where FxPhCO2(-) = 2,3-difluorobenzoate, ; 2,4
difluorobenzoate, ; 2,5-difluorobenzoate, ; 2,3,5-trifluorobenzoate, ), were
experimentally characterized with respect to solid-state structure, magnetic
properties and electrochemistry. By tuning the substituents of the benzoate
ligands using chlorine or fluorine atoms, the redox potential (E1/2) for
[Ru2(II,II)]/[Ru2(II,III)](+) varied over a wide range of potentials from -40 mV
to 360 mV (vs. Ag/Ag(+) in THF). This was dependent on (i) the number of ortho
substituents, i.e. non-, mono- and di-o-substituted groups, with quasi-Hammett
parameters for ortho-Cl and -F substitutions (sigmao = -0.272 and -0.217,
respectively) and (ii) the general Hammett constants, sigmam and sigmap, for each
group. The HOMO energy level calculated on the basis of the atomic coordinates of
the solid-state structure was strongly affected by Cl- and F-substitutions as
well as the redox potential in solution, which emphasizes the steric contribution
of ortho-substituents in the energy level giving a deviation of EHOMO < 0.3 eV
and <0.55 eV for the Cl- and F-series, respectively.
PMID- 25847190
TI - Characterizing and Overriding the Structural Mechanism of the Quizartinib
Resistant FLT3 "Gatekeeper" F691L Mutation with PLX3397.
AB - Tyrosine kinase domain mutations are a common cause of acquired clinical
resistance to tyrosine kinase inhibitors (TKI) used to treat cancer, including
the FLT3 inhibitor quizartinib. Mutation of kinase "gatekeeper" residues, which
control access to an allosteric pocket adjacent to the ATP-binding site, has been
frequently implicated in TKI resistance. The molecular underpinnings of
gatekeeper mutation-mediated resistance are incompletely understood. We report
the first cocrystal structure of FLT3 with the TKI quizartinib, which
demonstrates that quizartinib binding relies on essential edge-to-face aromatic
interactions with the gatekeeper F691 residue, and F830 within the highly
conserved Asp-Phe-Gly motif in the activation loop. This reliance makes
quizartinib critically vulnerable to gatekeeper and activation loop substitutions
while minimizing the impact of mutations elsewhere. Moreover, we identify
PLX3397, a novel FLT3 inhibitor that retains activity against the F691L mutant
due to a binding mode that depends less vitally on specific interactions with the
gatekeeper position. SIGNIFICANCE: We report the first cocrystal structure of
FLT3 with a kinase inhibitor, elucidating the structural mechanism of resistance
due to the gatekeeper F691L mutation. PLX3397 is a novel FLT3 inhibitor with in
vitro activity against this mutation but is vulnerable to kinase domain mutations
in the FLT3 activation loop.
PMID- 25847191
TI - Changes in Dpysl2 expression are associated with prenatally stressed rat
offspring and susceptibility to schizophrenia in humans.
AB - Exposure to stress during critical periods of fetal brain development is an
environmental risk factor for the development of schizophrenia in adult
offspring. In the present study, a repeated-variable stress paradigm was applied
to pregnant rats during the last week of gestation, which is analogous to the
second trimester of brain development in humans. Behavioral and proteomic
analyses were conducted in prenatally-stressed (PNS) adult offspring and non
stressed (NS) adult controls. In the behavioral tests, grooming behavior in the
social interaction test, line-crossing behavior in the open field test, and
swimming behavior in the forced swimming test were decreased in the PNS group.
Western blot analysis and immunohistochemical analysis revealed that the
expression of dihydropyrimidinase-like 2 (Dpysl2) or collapsin response mediator
protein 2 (Crmp2) was downregulated in the prefrontal cortex and hippocampus of
rats in the PNS group. Subsequently, single-nucleotide polymorphisms (SNPs) of
the human dihydropyrimidinase-like 2 (DPYSL2) gene were analyzed in a population.
Two functional SNPs (rs9886448 in the promoter region and rs2289593 in the exon
region) were associated with susceptibility to schizophrenia. The present
findings demonstrated that the downregulation of genes such as Dpysl2 and Dypsl3
in a rat model of prenatal stress may affect subsequent behavioral changes and
that polymorphisms of the DPYSL2 gene in humans may be associated with the
development of schizophrenia. Taken together with previous studies investigating
the association between the DPYSL2 gene and schizophrenia, the present findings
may contribute additional evidence regarding developmental theories of the
pathophysiology of schizophrenia.
PMID- 25847193
TI - Rice cyclophilin OsCYP18-2 is translocated to the nucleus by an interaction with
SKIP and enhances drought tolerance in rice and Arabidopsis.
AB - Cyclophilin 18-2 (CYP18-2) genes, homologues of human peptidyl-prolyl isomerase
like 1 (PPiL1), are conserved across multicellular organisms and
Schizosaccharomyces pombe. Although PPiL1 is known to interact with ski
interacting protein (SKIP), a transcriptional co-regulator and spliceosomal
component, there have been no functional analyses of PPiL1 homologues in plants.
Rice cyclophilin 18-2 (OsCYP18-2) bound directly to amino acids 56-95 of OsSKIP
and its binding was independent of cyclosporin A, a cyclophilin-binding drug.
Moreover, OsCYP18-2 exhibited PPIase activity regardless of its interaction with
OsSKIP. Therefore, the binding site for OsCYP18-2's interaction with SKIP was
distinct from the PPIase active site. OsCYP18-2's interaction with SKIP full
length protein enabled OsCYP18-2's translocation from the cytoplasm into the
nucleus and AtSKIP interacted in planta with both AtCYP18-2 and OsCYP18-2.
Drought and salt stress induced similar expression of OsCYP18-2 and OsSKIP.
Overexpression of OsCYP18-2 in transgenic rice and Arabidopsis thaliana plants
enhanced drought tolerance and altered expression and pre-mRNA splicing patterns
of stress-related genes in Arabidopsis under drought conditions. Furthermore,
OsCYP18-2 caused transcriptional activation with/without OsSKIP in the GAL4
system of yeast; thus the OsSKIP-OsCYP18-2 interaction has an important role in
the transcriptional and post-transcriptional regulation of stress-related genes
and increases tolerance to drought stress.
PMID- 25847194
TI - Recurrence after stapled haemorrhoidopexy.
PMID- 25847195
TI - "Wrap technique": a new operative procedure using a self-adhesive prosthesis for
laparoscopic ventral rectopexy.
AB - The aim of the present study was to describe and assess a new method of fixation
using a self-adhesive prosthesis (Adhesix(TM)) in laparoscopic ventral rectopexy
(LVR). The technical principles are based on a very low dissection and the
adhesive properties of the prosthesis which can be applied to the rectum without
stitches or staples. The prosthesis is made from polypropylene coated with a
synthetic hydrogel. The binding of the prosthesis to rectum and vagina takes
place in a wet environment after a few minutes and enables the shaping of the
mesh on the surface of the rectum (wrap effect). Between March 2010 and March
2013, 41 patients were operated on using LVR with a self-adhesive prosthesis. The
effectiveness of prosthesis fixation was evaluated in a subset of 27 patients
suffering from complete rectal prolapse. With a median follow-up of 30 months,
there were no major complications and no recurrence. In this initial experience,
LVR with a self-adhesive prosthesis does not increase the risk of recurrence. No
undesirable effects were associated with the prosthesis.
PMID- 25847196
TI - Thrombin generation measured as thrombin-antithrombin complexes predicts clinical
outcomes in patients with cirrhosis.
AB - AIM: Hypercoagulability has been detected in patients with cirrhosis yet its
clinical significance remains unclear. We investigated the association of
hypercoagulability with clinical outcomes in patients with cirrhosis. METHODS:
Thrombin-antithrombin (TAT) complexes as thrombin generation (TG) marker, D
dimer, antithrombin (AT), protein C, protein S, international normalized ratio
(INR), activated partial thromboplastin time, fibrinogen, Child-Pugh class and
Model for End-Stage Liver Disease (MELD) were evaluated. Two different
multivariate analyses were performed: one not including MELD (model 1) and one
including MELD and excluding INR (model 2). RESULTS: Eighty-one patients (Child
Pugh class A/B/C: 27/27/27) and 40 healthy subjects were enrolled. Only
TauAlphaTau and AT were independently associated with increasing liver disease
severity. Increased TAT levels and MELD score were significantly associated with
ascites and varices at baseline. Independent predictors of follow-up events were:
TAT and MELD score for new-onset ascites; TAT and AT for variceal bleeding (VB);
TAT and AT for portal vein thrombosis (PVT); and TAT and MELD for mortality. TAT
equaled MELD in mortality prediction at 12 and 18 months. TAT cut-offs at 5.35,
14.6, 13.5 and 9.25 ng/mL identified patient groups with significantly higher
probability of new-onset ascites, VB, PVT and mortality, respectively.
CONCLUSION: Increased TG is strongly correlated with portal hypertension-related
complications, PVT and mortality in patients with cirrhosis. Measuring TG by TAT
could enable risk stratification and institution of preventive strategies to
improve clinical outcomes.
PMID- 25847197
TI - Concordance of bacterial communities of two tick species and blood of their
shared rodent host.
AB - High-throughput sequencing is revealing that most macro-organisms house diverse
microbial communities. Of particular interest are disease vectors whose
microbiome could potentially affect pathogen transmission and vector competence.
We investigated bacterial community composition and diversity of the ticks
Dermacentor variabilis (n = 68) and Ixodes scapularis (n = 15) and blood of their
shared rodent host, Peromyscus leucopus (n = 45) to quantify bacterial diversity
and concordance. The 16S rRNA gene was amplified from genomic DNA from field
collected tick and rodent blood samples, and 454 pyrosequencing was used to
elucidate their bacterial communities. After quality control, over 300 000
sequences were obtained and classified into 118 operational taxonomic units
(OTUs, clustered at 97% similarity). Analysis of rarefied communities revealed
that the most abundant OTUs were tick species-specific endosymbionts, Francisella
and Rickettsia, and the commonly flea-associated bacterium Bartonella in rodent
blood. An Arsenophonus and additional Francisella endosymbiont were also present
in D. variabilis samples. Rickettsia was found in both tick species but not in
rodent blood, suggesting that it is not transmitted during feeding. Bartonella
was present in larvae and nymphs of both tick species, even those scored as
unengorged. Relatively, few OTUs (e.g. Bartonella, Lactobacillus) were found in
all sample types. Overall, bacterial communities from each sample type were
significantly different and highly structured, independent of their dominant
OTUs. Our results point to complex microbial assemblages inhabiting ticks and
host blood including infectious agents, tick-specific endosymbionts and
environmental bacteria that could potentially affect arthropod-vectored disease
dynamics.
PMID- 25847198
TI - An acoustic feature-based similarity scoring system for speech rehabilitation
assistance.
AB - The purpose of this study is to develop a tool to assist speech therapy and
rehabilitation, which focused on automatic scoring based on the comparison of the
patient's speech with another normal speech on several aspects including pitch,
vowel, voiced-unvoiced segments, strident fricative and sound intensity. The
pitch estimation employed the use of cepstrum-based algorithm for its robustness;
the vowel classification used multilayer perceptron (MLP) to classify vowel from
pitch and formants; and the strident fricative detection was based on the major
peak spectral intensity, location and the pitch existence in the segment. In
order to evaluate the performance of the system, this study analyzed eight
patient's speech recordings (four males, four females; 4-58-years-old), which had
been recorded in previous study in cooperation with Taipei Veterans General
Hospital and Taoyuan General Hospital. The experiment result on pitch algorithm
showed that the cepstrum method had 5.3% of gross pitch error from a total of
2086 frames. On the vowel classification algorithm, MLP method provided 93%
accuracy (men), 87% (women) and 84% (children). In total, the overall results
showed that 156 tool's grading results (81%) were consistent compared to 192
audio and visual observations done by four experienced respondents. Implication
for Rehabilitation Difficulties in communication may limit the ability of a
person to transfer and exchange information. The fact that speech is one of the
primary means of communication has encouraged the needs of speech diagnosis and
rehabilitation. The advances of technology in computer-assisted speech therapy
(CAST) improve the quality, time efficiency of the diagnosis and treatment of the
disorders. The present study attempted to develop tool to assist speech therapy
and rehabilitation, which provided simple interface to let the assessment be done
even by the patient himself without the need of particular knowledge of speech
processing while at the same time, also provided further deep analysis of the
speech, which can be useful for the speech therapist.
PMID- 25847199
TI - [Aspirin hypersensitivity: characteristics and diagnostic approach].
AB - INTRODUCTION: In routine medical practice, the diagnosis of aspirin
hypersensitivity (AH) remains difficult. No clinical feature or biomarker is
available to reliably confirm this diagnosis and oral provocation tests (OPT) are
rarely performed. AIM: To compare asthmatics with and without AH. METHOD: The
clinical characteristics of 21 asthmatics with and 24 without AH respectively
were determined. AH was defined by a positive OPT. A full blood count was done
before and 24 hours after the OPT. RESULTS: The medical history was associated
with a weak sensitivity (52%) and a good specificity (96%) for assessing the
diagnosis of AH. There was a higher prevalence of AH in women, and a higher
frequency of allergic rhinitis in AH, but no characteristic was useful to
facilitate the diagnosis of AH in asthmatic patients. Our results demonstrate
higher values of platelets in AH patients. Following OPT, in AH patients only, a
decrease in blood eosinophils and an increase in neutrophils was observed.
CONCLUSIONS: These results confirm that the diagnosis of AH is challenging, with
the history having only weak sensitivity. The observation that fluctuations in
eosinophils and neutrophils occur following OPT in AH patients only warrants
further investigations and suggests a rapid pro-inflammatory role for aspirin.
PMID- 25847200
TI - [Is the asthmatic patient competent to manage his disease? A study of 280
patients in Seine-Saint-Denis, France].
AB - INTRODUCTION: The correct use of medication and the ability to assess the
severity of the disease and to react appropriately in the case of exacerbation
are essential objectives in the management of asthma patients. This study,
conducted in a school of asthma in Seine-Saint-Denis, aims to measure the
influence of socio-demographic and clinical factors, before any educational
process, on these four security skills. METHODS: A prospective observational
study concerning 280 consecutive patients managed between 2008 and 2011 (70 %
women, mean age: 44 years [14-85 years]; deprivation: 48 %; born abroad: 39 %,
low level of education: 23 %). The initial educational diagnosis was compared
with the clinical and socio-demographic characteristics. RESULTS: In relation to
asthma control, social characteristics (unemployment, deprivation), geographic or
ethnic origin and educational level significantly influence the command of all or
some of the security skills. In medical terms, a period of evolution of the
disease of less than 10 years, outpatient follow-up without specialized
monitoring and the absence of recent exacerbations also appear as predictors of
inappropriate conduct in the management of the disease. CONCLUSIONS: This study
suggests new priority targets for therapeutic education in asthma.
PMID- 25847201
TI - [AIRBAg study: preliminary results after one year of screening for COPD in dairy
farmers].
AB - INTRODUCTION: The AIRBAg study screens for bronchial obstruction in dairy
farmers. We present the preliminary results after one year. METHODS: A
prospective screening study based on questionnaires and electronic mini
spirometry (Neo-6((r))) that includes a representative sample of dairy farmers
from the departments of Morbihan and Ile-et-Vilaine in Brittany. The dairy
farmers had an occupational medicine appointment and, if they demonstrated at
least one marker of possible bronchial obstruction (chronic cough, chronic
bronchitis, dyspnoea, wheezing, FEV1/FEV6<0.8), they were referred to a
pulmonologist. The data we present here were extracted from the occupational
medicine appointments because the pulmonologists' appointments are still running.
RESULTS: Among the 277 dairy farmers included, 125 (45%) demonstrated "possible
bronchial obstruction". The total score of the CAT questionnaire was higher in
these farmers (9.1+/-6.2 versus 5.8+/-4.0; P<0.0001). In multivariate analysis
markers of "possible bronchial obstruction" were eczema, manual foddering and
duration of mechanical straw litter spreading. CONCLUSION: Occupational medicine
appointments identified markers of "possible bronchial obstruction". We will have
the complete results from AIRBAg study in 2015.
PMID- 25847202
TI - [Acceptability and compliance to long-term continuous positive pressure
treatment].
AB - INTRODUCTION: Compliance with continuous positive pressure treatment (CPAP) is a
determining factor in the management of the obstructive sleep apnea syndrome
(OSAS). Long-term compliance has been poorly studied. METHODS: The probability of
long-term continuation of CPAP was evaluated retrospectively by an analysis of
survival in 252 patients treated by CPAP after a screening of 472 patients during
the years 2002 and 2003. RESULTS: Twenty-eight patients fulfilling the criteria
for CPAP immediately refused the treatment. The mean follow-up for the 252
treated patients was 76.9+/-46.4 months, with 38 patients having died and 75
having discontinued treatment during the period. The 136 patients who continued
treatment used CPAP for a mean of 7.4+/-1.6hours daily. The probability of
continuing treatment was 71% at 5 years and 68% at 10 years. The severity of OSAS
was a predictive factor for long-term CPAP compliance, with a 10-year compliance
of 82% in patients having an apnoea/hypopnoea index >60, versus 68% with an index
between 30-60 and 44% with an index <30. CONCLUSION: Long-term CPAP treatment is
globally well accepted, with a 68% probability of continuing treatment for 10
years, particularly in the most severely affected patients. Long-term daily
compliance is very satisfactory.
PMID- 25847203
TI - [Chemotherapy at the end of life for patients with lung cancer. A practice
analysis].
AB - RATIONALE: Few studies have analyzed the aggressiveness of the care (continuation
of active treatments) at the end of life in patients with lung cancer. The
objective of this study was to assess practices in this setting in a university
department of respiratory medicine. PATIENTS AND METHODS: This retrospective
study has consecutively included all patients who were managed for lung cancer
and died over a period of 18 months. The analysis focused on the characteristics
of the patients, the modalities of cancer treatment and the delays between the
last active treatment and death. RESULTS: The overall median survival of the 94
patients included was 9.6 months; 92% of patients having received at least one
active treatment. During the 4 and 2 weeks periods preceding death, respectively
55% and 22% of the patients received active treatments. The median time between
the last day of active treatment and death was 27 days. CONCLUSION: These
results, in concordance with the published data, showed that end of life active
treatment in patients with lung cancer is a complex problem. We need prospective
multicentric studies, with testing tools allowing better sharing of the decisions
on active treatment between the medical team, the patient and his family.
PMID- 25847204
TI - [Prevalence of tobacco smoking in primary and secondary schools in the Department
of Dakar, Senegal].
AB - INTRODUCTION: Tobacco smoke is a global health problem, and the largest avoidable
cause of death in the world. The objective of our study was to determine the
prevalence of tobacco smoking in schools in Dakar area (Senegal). MATERIEL AND
METHODS: This descriptive and analytical cross-sectional study was performed from
September 2011 to June 2012 in 27 schools of the Dakar area. RESULTS: We
questioned 1654 students over a 9-month school period. The mean age was 15+/
2.5years (range 11-22). The sample included 848 boys (51.3 %), therefore a sex
ratio of 1.05. There were 68 smokers (4.1 %) and 60 ex-smokers (3.6 %). The mean
age of the smokers was 16.9+/-2.2years (range 11-22) with a male preponderance of
70.6 % (n=48). Smoking in family members was the initiating factor most
frequently reported by smokers (25 %). The average age of ex-smokers was 16.4+/
2years. Fear of parents' reactions was the most frequently invoked reason for
stopping smoking (41.7 %). CONCLUSION: This study confirms the reality of smoking
among school children in Senegal and highlights the urgency of the installation
of a prevention policy near the young people.
PMID- 25847205
TI - [Mesothelioma and familial Mediterranean fever: A relationship?].
AB - INTRODUCTION: The majority of pleural and peritoneal mesotheliomas are linked to
asbestos exposure but, in around 20% of cases, no history of such exposure is
found. Periodic disease is associated with recurrent serositis, which could favor
the development of mesothelioma. CASE REPORT: We report a case of pleural
mesothelioma in a 50-year-old Lebanese woman, with no detectable exposure to
asbestos but suffering from periodic disease (familial Mediterranean fever) with
recurrent episodes of serositis. DISCUSSION: Many cases of peritoneal
mesothelioma in patients with FMF are reported in the literature. This is the
second reported case of pleural mesothelioma associated with periodic disease.
Because of the low incidence of both diseases, further publications are required
to support the hypothesis of a causal link. It is important, therefore, that all
cases of an association of periodic disease and mesothelioma are reported.
PMID- 25847206
TI - [Chronic Farmer's lung disease with emphysema].
AB - INTRODUCTION: Farmer's lung (FL) is the most common type of hypersensitivity
pneumonitis (HP), with an estimated prevalence of between 0.5 and 1.5% in dairy
farmers. In chronic FL, fibrotic sequelae are widely described in the literature
although our experience and occasional epidemiological studies emphasize an
increased risk of developing emphysema in these patients. CASE REPORT: We report
a case of FL in a 37-year-old patient with typical clinical features (exertional
dyspnoea, lymphocytic alveolitis and computed tomography appearances) together
with proven allergen exposure. This patient developed early pulmonary emphysema
probably due to intermittent massive exposure to antigens and to bacterial and
fungal micro-organisms. CONCLUSION: The current classification of HP
differentiates acute, subacute and chronic forms but does not take account of the
role of the mode of exposure and the evolution of the disease. The prognosis and
evolution of HP seem to be dependent on the type and pattern of exposure. A new
classification with two clusters has been suggested: in type 1, massive and
intermittent exposure, as in FL, may lead to emphysema with chronic airflow
obstruction and, in type 2, chronic exposure to a low level, as in bird fanciers,
may lead to fibrosis with a restrictive pattern.
PMID- 25847207
TI - [Noninvasive ventilation: efficacy of a new ventilatory mode in patients with
obesity-hypoventilation syndrome].
AB - Noninvasive ventilation is recommended to correct the nocturnal hypoventilation
and relieve the symptoms of patients with the obesity-hypoventilation syndrome
(OHS). The benefits of fixed pressure ventilation (S/T technology) are recognized
but limited on account of the variability of nocturnal ventilatory requirements.
The new technique AVAPS-AE (automatic EPAP) allows adjustment of the pressure
according to the volume currently targeted. Its efficacy has not yet been
evaluated. Our objectives are to evaluate firstly, whether AVAPS-AE optimizes the
benefits of S/T technology on sleep architecture and quality, secondly, whether
these benefits are associated with an improvement in gas exchange, symptoms,
exercise tolerance, level of physical activity and quality of life of patients
with OHS. In this multicenter trial, 60 newly diagnosed patients with OHS will be
randomized to the control (S/T) and trial (AVAPS-AE) groups. A standardized
titration procedure will be followed for the calibration of the ventilators.
Functional evaluations (polysomnography, blood gases, impedance measurements and
walking tests), questionnaires (physical activity, quality of life, quality of
sleep and daytime somnolence) visual scales (fatigue, headaches) and a recording
of activity will be undertaken after two months of ventilation.
PMID- 25847208
TI - [Multiple lung nodules and mediastinal widening of unusual etiology].
PMID- 25847209
TI - [Diffuse and circumferential expiratory collapse].
PMID- 25847210
TI - [Echocardiography and pulmonary hypertension: experience of the competence centre
in Tours, France].
PMID- 25847211
TI - Lipoxin A4 inhibits proliferation and inflammatory cytokine/chemokine production
of human epidermal keratinocytes associated with the ERK1/2 and NF-kappaB
pathways.
AB - BACKGROUND: Current in vitro studies show that lipoxin A4 (LXA4) has multiple
biological functions including inhibiting cell proliferation and inflammatory
cytokine production. Our previous studies showed LXA4 could inhibit the
expression of IL-6 and IL-8 in normal human epidermal keratinocytes (NHEKs).
However, more specific effects including regulation of cell proliferation and
anti-inflammatory mechanisms of LXA4 in NHEKs have not been previously studied.
OBJECTIVE: We proposed to investigate the effects of LXA4 on cell proliferation
and inflammatory cytokine/chemokine production in NHEKs, and the possible
molecular mechanisms of cell cycle and anti-inflammatory signal transduction
pathway. METHODS: NHEKs were stimulated with LPS, with or without preincubation
with LXA4. Cell proliferation and cell cycle of NHEKs were examined by WST-8,
CFSE assay and DNA staining, respectively. The mRNA and protein levels of
inflammatory cytokines were quantified by real-time quantitative PCR and ELISA.
The expressions of signaling proteins cyclin D1, P16INK4A, ERK1/2 and NF-kappaB
p65 were analyzed using Western blotting. RESULTS: Cell proliferation and
inflammatory cytokine/chemokine production of NHEKs were suppressed by LXA4,
which caused G0/G1 phase cell cycle arrest in NHEKs. The expression of cyclin D1
was down-regulated by LXA4, contrary to the results of P16INK4A. The ERK1/2
phosphorylation and NF-kappaB-p65 nuclear translocation of NHEKs were both
suppressed by LXA4. CONCLUSION: Cell growth and inflammatory cytokine/chemokine
production of NHEKs were inhibited by LXA4, and the inhibitory effects might be
associated with the mechanisms of cyclin D1/P16INK4A, ERK1/2 and NF-kappaB signal
transduction pathway.
PMID- 25847212
TI - Multi-location wheat stripe rust QTL analysis: genetic background and epistatic
interactions.
AB - KEY MESSAGE: Epistasis and genetic background were important influences on
expression of stripe rust resistance in two wheat RIL populations, one with
resistance conditioned by two major genes and the other conditioned by several
minor QTL. Stripe rust is a foliar disease of wheat (Triticum aestivum L.) caused
by the air-borne fungus Puccinia striiformis f. sp. tritici and is present in
most regions around the world where commercial wheat is grown. Breeding for
durable resistance to stripe rust continues to be a priority, but also is a
challenge due to the complexity of interactions among resistance genes and to the
wide diversity and continuous evolution of the pathogen races. The goal of this
study was to detect chromosomal regions for resistance to stripe rust in two
winter wheat populations, 'Tubbs'/'NSA-98-0995' (T/N) and 'Einstein'/'Tubbs'
(E/T), evaluated across seven environments and mapped with diversity array
technology and simple sequence repeat markers covering polymorphic regions of
~1480 and 1117 cM, respectively. Analysis of variance for phenotypic data
revealed significant (P < 0.01) genotypic differentiation for stripe rust among
the recombinant inbred lines. Results for quantitative trait loci/locus (QTL)
analysis in the E/T population indicated that two major QTL located in
chromosomes 2AS and 6AL, with epistatic interaction between them, were
responsible for the main phenotypic response. For the T/N population, eight QTL
were identified, with those in chromosomes 2AL and 2BL accounting for the largest
percentage of the phenotypic variance.
PMID- 25847213
TI - Cardiac Response During Auditory Selective Attention to Tones and Affective
Sounds.
AB - We conducted an experiment to determine if attention to affective sounds showed a
lateral bias. Twenty-two participants were instructed to respond to one of two
pure tones presented monaurally and to a set of pleasant and unpleasant sounds
from the International Affective Digitized Sounds set. Participants were
instructed to respond to pleasant or unpleasant sounds in the right or left ear,
attending to pleasant/right, pleasant/left, unpleasant/right, and unpleasant/left
sounds in separate blocks. Evoked cardiac response to the tones showed
significant cardiac deceleration in response to attended sounds in the attended
ear. In addition, pleasant sounds elicited significant cardiac deceleration when
attended in the right ear, but not in the left. Unpleasant sounds elicited
significant cardiac deceleration when attended in both ears. Consistent with the
anterior valence hypothesis, our data suggests that pleasant sounds are mainly
processed in the left hemisphere, but in contrast to this hypothesis, unpleasant
sounds are processed bilaterally.
PMID- 25847214
TI - Social Cultivation of Vaccine Refusal and Delay among Waldorf (Steiner) School
Parents.
AB - U.S. media reports suggest that vastly disproportionate numbers of un- and under
vaccinated children attend Waldorf (private alternative) schools. After
confirming this statistically, I analyzed qualitative and quantitative
vaccination-related data provided by parents from a well-established U.S. Waldorf
school. In Europe, Waldorf-related non-vaccination is associated with
anthroposophy (a worldview foundational to Waldorf education)-but that was not
the case here. Nor was simple ignorance to blame: Parents were highly educated
and dedicated to self-education regarding child health. They saw vaccination as
variously unnecessary, toxic, developmentally inappropriate, and profit driven.
Some vaccine caution likely predated matriculation, but notable post-enrollment
refusal increases provided evidence of the socially cultivated nature of vaccine
refusal in the Waldorf school setting. Vaccine caution was nourished and
intensified by an institutionalized emphasis on alternative information and by
school community norms lauding vaccine refusal and masking uptake. Implications
for intervention are explored.
PMID- 25847215
TI - Are antidepressants mood destabilizers?
PMID- 25847216
TI - Wine protein haze: mechanisms of formation and advances in prevention.
AB - Protein haze is an aesthetic problem in white wines that can be prevented by
removing the grape proteins that have survived the winemaking process. The haze
forming proteins are grape pathogenesis-related proteins that are highly stable
during winemaking, but some of them precipitate over time and with elevated
temperatures. Protein removal is currently achieved by bentonite addition, an
inefficient process that can lead to higher costs and quality losses in
winemaking. The development of more efficient processes for protein removal and
haze prevention requires understanding the mechanisms such as the main drivers of
protein instability and the impacts of various wine matrix components on haze
formation. This review covers recent developments in wine protein instability and
removal and proposes a revised mechanism of protein haze formation.
PMID- 25847217
TI - Understanding expressions of public grief: 'mourning sickness', 'grief-lite', or
something more?
PMID- 25847218
TI - Higher risk for adverse obstetric outcomes among immigrants of African and Asian
descent: a comparison study at a low-risk maternity hospital in Norway.
AB - BACKGROUND: Immigrants have higher risks for some adverse obstetric outcomes, and
40 percent of women giving birth at the low-risk maternity ward in Baerum
Hospital, Norway, are immigrants. This study compared obstetric outcomes between
immigrants and ethnic Norwegians giving birth in a low-risk setting. METHODS:
This was a population-based study linking the Medical Birth Registry of Norway to
Statistics Norway. The study included the first registered birth during the study
period to immigrant and ethnic Norwegian women at Baerum Hospital from 2006 to
2010. The main outcome measures were onset of labor, operative vaginal delivery,
cesarean delivery, episiotomy, postpartum bleeding > 500 mL, epidural analgesia,
labor dystocia, gestational age, meconium-stained liquor, 5-minute Apgar score,
birthweight, and transfer to a neonatal intensive care unit. RESULTS: A total of
11,540 women originating from 141 countries were divided into seven groups.
Compared with Norwegians, women from East, Southeast, and Central Asia had
increased risk for operative vaginal delivery, postpartum bleeding, and low Apgar
score. The African women had increased risk for postterm birth, meconium-stained
liquor, episiotomy, operative vaginal delivery, emergency cesarean delivery,
postpartum bleeding, low Apgar score, and low birthweight. Women from South and
Western Asia had increased risk for low birthweight. CONCLUSION: Obstetric
outcomes of immigrants differ significantly from those of Norwegians, even in a
low-risk maternity unit. Thus, immigrant women would benefit from more targeted
care during pregnancy and childbirth, even in low-risk settings.
PMID- 25847219
TI - The low oxygen, oxidative and osmotic stress responses synergistically act
through the ethylene response factor VII genes RAP2.12, RAP2.2 and RAP2.3.
AB - The ethylene response factor VII (ERF-VII) transcription factor RELATED TO
APETALA2.12 (RAP2.12) was previously identified as an activator of the ALCOHOL
DEHYDROGENASE1 promoter::luciferase (ADH1-LUC) reporter gene. Here we show that
overexpression of RAP2.12 and its homologues RAP2.2 and RAP2.3 sustains ABA
mediated activation of ADH1 and activates hypoxia marker genes under both anoxic
and normoxic conditions. Inducible expression of all three RAP2s conferred
tolerance to anoxia, oxidative and osmotic stresses, and enhanced the sensitivity
to abscisic acid (ABA). Consistently, the rap2.12-2 rap2.3-1 double mutant showed
hypersensitivity to both submergence and osmotic stress. These findings suggest
that the three ERF-VII-type transcription factors play roles in tolerance to
multiple stresses that sequentially occur during and after submergence in
Arabidopsis. Oxygen-dependent degradation of RAP2.12 was previously shown to be
mediated by the N-end rule pathway. During submergence the RAP2.12, RAP2.2 and
RAP2.3 are stabilized and accumulates in the nucleus affecting the transcription
of stress response genes. We conclude that the stabilized RAP2 transcription
factors can prolong the ABA-mediated activation of a subset of osmotic responsive
genes (e.g. ADH1). We also show that RAP2.12 protein level is affected by the
REALLY INTERESTING GENE (RING) domain containing SEVEN IN ABSENTIA of Arabidopsis
thaliana 2 (SINAT2). Silencing of SINAT1/2 genes leads to enhanced RAP2.12
abundance independently of the presence or absence of its N-terminal degron.
Taken together, our results suggest that RAP2.12 and its homologues RAP2.2 and
RAP2.3 act redundantly in multiple stress responses. Alternative protein
degradation pathways may provide inputs to the RAP2 transcription factors for the
distinct stresses.
PMID- 25847220
TI - Mutation of CHRNA2 in a family with benign familial infantile seizures: Potential
role of nicotinic acetylcholine receptor in various phenotypes of epilepsy.
AB - Nicotinic acetylcholine receptor genes are involved mainly in nocturnal frontal
epilepsy. Despite extensive studies, to date, the alpha2 subunit did not show a
strong association with this peculiar epileptic phenotype. We report CHRNA2
missense mutation in a family with benign familial infantile seizures (BFIS).
TrueSeq Custom Amplicon (TSCA) sequencing approach was used to screen 10 ion
channel genes in patients with idiopathic epilepsies. TSCA revealed a
heterozygous single-nucleotide substitution in CHRNA2 gene (c.1126 C>T; p.
Arg376Trp) that segregated in a family with BFIS; based on bio-informatics
inspection, the change was predicted to be pathogenic. The investigated family
includes parents and their three daughters. In affected individuals, seizures
started between 6 and 24 months of age. Seizures were mainly in cluster and well
controlled. Outcome was good in all subjects. Even if nicotinic acetylcholine
receptor genes are traditionally associated with autosomal dominant nocturnal
frontal lobe epilepsy (ADNFLE), this single-family description can open new
possibilities in the genetic diagnosis, molecular characterization, and
management of CHRNA2-related epilepsy. The pathogenic conversion of arginine 376
to tryptophan alters all of these interactions in the cytoplasmic domain, never
reported to be involved in epileptogenic mechanism. Further functional tests will
be necessary to strongly relate CHRNA2 mutation with BFIS phenotype.
PMID- 25847222
TI - "(Diphosphine)Nickel"-catalyzed negishi cross-coupling: an experimental and
theoretical study.
AB - The use of a strongly donating "(bis-dialkylphosphine)Ni" fragment promotes the
catalytic coupling of a large range of ArCl and ArZnCl derivatives under mild
conditions. Stoichiometric mechanistic investigations and DFT calculations prove
that a Ni(0) /Ni(II) cycle is operative in this system.
PMID- 25847221
TI - Myasthenia gravis: descriptive analysis of life-threatening events in a recent
nationwide registry.
AB - BACKGROUND AND PURPOSE: Myasthenia gravis (MG) may become life-threatening if
patients have respiratory insufficiency or dysphagia. This study aimed to
determine the incidence, demographic characteristics, risk factors, response to
treatment and outcome of these life-threatening events (LTEs) in a recent,
population-based sample of MG patients. METHODS: A retrospective analysis of MG
patients who presented with an LTE between 2000 and 2013 was performed.
Participants were identified from a neuromuscular diseases registry in Spain that
includes 648 patients with MG (NMD-ES). RESULTS: Sixty-two (9.56%) patients had
an LTE. Thirty-two were classified as class V according to the MG Foundation of
America, and 30 as class IVB. Fifty per cent were previously diagnosed with MG
and median duration of the disease before the LTE was 24 months (3-406). The most
common related factor was infection (n = 18). All patients received intravenous
human immunoglobulin; 11 had a second infusion and six had plasma exchange.
Median time to feeding tube removal was 13 days (1-434). Median time to weaning
from ventilation was 12 days (3-176), and it was significantly shorter in late
onset MG (>=50 years) (P = 0.019). LTEs improved <2 weeks in 55.8% but did not
improve until after 1 month in 20% of patients. Four patients died. No other
factors influenced mortality or duration of LTEs. CONCLUSIONS: The percentage of
LTEs in MG patients was low, particularly amongst those previously diagnosed and
treated for the disease. The significant percentage of treatment-resistant LTEs
indicates that more effective treatment approaches are needed for this vulnerable
sub-population.
PMID- 25847223
TI - IL-6 blockade reverses the abnormal STAT activation of peripheral blood
leukocytes from rheumatoid arthritis patients.
AB - Considering the interplay of multiple STATs in response to cytokines, we
investigated how IL-6 and its blocking affect STAT signaling in rheumatoid
arthritis (RA). Leukocytes obtained from RA patients before and after tocilizumab
treatment and healthy donors (HDs) were cytokine-stimulated and STAT
phosphorylation was analyzed by cytometry. RA patients had significantly fewer
pSTAT1+, pSTAT3+, and pSTAT6+ monocytes and pSTAT5+ lymphocytes than HDs. After
24weeks of treatment, percentages of IFNgamma-induced pSTAT1+ and IL-10-induced
pSTAT3+ monocytes in RA patients increased, reaching levels comparable to HDs.
pSTAT1+ and pSTAT3+ cells correlated inversely with RA disease activity index and
levels of pSTAT+ cells at baseline were higher in patients with good EULAR
response to tocilizumab. IFNgamma-induced pSTAT1+ cells correlated inversely with
memory T cells and anti-CCP levels. IL-10-induced pSTAT3+ cells correlated with
Treg/Teff ratio. Our findings suggest that IL-6 blocking reduces the inflammatory
mechanisms through the correction of STAT1 and STAT3 activation status.
PMID- 25847224
TI - Projected future distribution of date palm and its potential use in alleviating
micronutrient deficiency.
AB - BACKGROUND: Micronutrient deficiency develops when nutrient intake does not match
nutritional requirements for maintaining healthy tissue and organ functions which
may have long-ranging effects on health, learning ability and productivity.
Inadequacy of iron, zinc and vitamin A are the most important micronutrient
deficiencies. Consumption of a 100 g portion of date flesh from date palm
(Phoenix dactylifera L.) has been reported to meet approximately half the daily
dietary recommended intake of these micronutrients. This study investigated the
potential distribution of P. dactylifera under future climates to address its
potential long-term use as a food commodity to tackle micronutrient deficiencies
in some developing countries. RESULTS: Modelling outputs indicated large shifts
in areas conducive to date palm cultivation, based on global-scale alteration
over the next 60 years. Most of the regions suffering from micronutrient
deficiencies were projected to become highly conducive for date palm cultivation.
CONCLUSIONS: These results could inform strategic planning by government and
agricultural organizations by identifying areas to cultivate this nutritionally
important crop in the future to support the alleviation of micronutrient
deficiencies.
PMID- 25847226
TI - Iatrogenic injury to the sciatic nerve during surgical repair of proximal
hamstring avulsion.
PMID- 25847225
TI - Prehospital and Emergency Care: Updates from the Disease Control Priorities,
Version 3.
AB - BACKGROUND: It is increasingly understood that emergency care systems can be cost
effective in low- and middle-income countries (LMICs). The development of such
systems, however, is still a work in progress. This article updates previous work
in providing the most recent estimates of the burden of disease sensitive to
emergency care, the current state of knowledge on the feasibility of emergency
care, effect on outcomes, and cost-effectiveness in LMICs, and future directions
for research, policy, and implementation. METHODS: We calculated the potential
impact of prehospital and emergency care systems using updated and revised data
based on the global burden of disease study. We then assessed the state of
current knowledge and potential future directions for research and policy by
conducting a review of the literature on current systems in LMICs. RESULTS:
According to these newest updates, 24 million deaths related to emergency medical
conditions occur in LMICs annually, accounting for an estimated 932 million years
of life lost. Evidence shows that multiple emergency care models can function in
different local settings, depending on resources and urbanicity. Emergency care
can significantly improve mortality rates from emergent conditions and be highly
cost-effective. Further research is needed on implementation of emergency care
systems as they become a necessary reality in developing nations worldwide.
CONCLUSIONS: Emergency care implementation in LMICs presents both challenges and
opportunities. Investment in evidence-based emergency care, research on
implementation, and system coordination in LMICs could lead to a more cost- and
outcome-effective emergency care system than exists in advanced economies.
PMID- 25847227
TI - Open-label prospective study of the safety and efficacy of glass-based yttrium 90
radioembolization for infiltrative hepatocellular carcinoma with portal vein
thrombosis.
AB - BACKGROUND: The safety and efficacy of yttrium 90 ((90) Y) therapy for
unresectable infiltrative hepatocellular carcinoma (HCC) with portal vein
thrombosis (PVT) requires further evaluation. METHODS: A prospective, single
center safety and feasibility study recruited patients with unresectable
(Barcelona Clinic Liver Cancer stage C) infiltrative HCC with PVT. Safety was
assessed according to Common Terminology Criteria for Adverse Events version 4.0.
Overall survival (OS) and time to progression (TTP) were measured from the first
(90) Y therapy. Survival analysis was performed with Kaplan-Meier estimation.
Prognostic factors were tested with a log-rank test and Cox proportional
regression analysis. RESULTS: Overall, 45 patients were recruited, and 30
patients who met the study's inclusion criteria underwent glass-based (90) Y
therapy. Four patients (13%) had transient hepatobiliary toxicity (grade >= 2).
Ten patients (33%) had related emergency department visits, with 5 patients (17%)
requiring short-term hospitalization. No radiation pneumonitis, gastrointestinal
ulceration, or procedure-related mortality occurred. The median OS was 13 months
(95% confidence interval, 4.4-22 months) with a TTP of 9 months (95% confidence
interval, 6.2-13.1 months). Absence of ascites, an international normalized ratio
< 1.2, an Eastern Cooperative Oncology Group (ECOG) performance status of 0,
Child-Pugh class A, a macroaggregated albumin lung shunt fraction (LSF) < 10%,
and no hepatobiliary toxicity were significant predictors of prolonged OS
according to a univariate analysis (P < .05). A multivariate analysis found an
ECOG performance status of 0, Child-Pugh class A, an LSF < 10%, and lack of
transient hepatobiliary toxicity (grade >= 2) to be independent predictors of
prolonged OS (P < .05). An ECOG performance status of 0, Child-Pugh class A, and
an LSF < 10% were also predictors of prolonged TTP according to the multivariate
analysis (P < .05). CONCLUSIONS: In patients with unresectable infiltrative HCC
and PVT, (90) Y therapy appears to be a safe and viable therapy.
PMID- 25847228
TI - Dependence Assessment in Human Reliability Analysis Using Evidence Theory and
AHP.
AB - Dependence assessment among human errors in human reliability analysis (HRA) is
an important issue. Many of the dependence assessment methods in HRA rely heavily
on the expert's opinion, thus are subjective and may sometimes cause
inconsistency. In this article, we propose a computational model based on the
Dempster-Shafer evidence theory (DSET) and the analytic hierarchy process (AHP)
method to handle dependence in HRA. First, dependence influencing factors among
human tasks are identified and the weights of the factors are determined by
experts using the AHP method. Second, judgment on each factor is given by the
analyst referring to anchors and linguistic labels. Third, the judgments are
represented as basic belief assignments (BBAs) and are integrated into a fused
BBA by weighted average combination in DSET. Finally, the CHEP is calculated
based on the fused BBA. The proposed model can deal with ambiguity and the degree
of confidence in the judgments, and is able to reduce the subjectivity and
improve the consistency in the evaluation process.
PMID- 25847229
TI - 4q21 microdeletion in a patient with epilepsy and brain malformations.
PMID- 25847230
TI - Melamine foam in Dentistry.
PMID- 25847231
TI - Expression of stress-related proteins in Sediminibacterium sp. growing under
planktonic conditions.
AB - Aggregation is a common trait of bacteria in natural and engineered biological
systems. Microbial aggregates, such as flocs, granules, and biofilms, are
spatially heterogeneous environments. It is generally observed that by growing
under aggregated conditions bacteria respond and adapt to environmental stress
better than free-swimming bacteria of the same species. We performed a proteomic
analysis of a strain of Sediminibacterium, isolated from activated sludge, which
grew planktonically in diluted culture media and in an aggregated form in media
containing a high concentration of organic substrate. Auto-aggregation was also
observed in the presence of pyruvate in dilute media. Expression of a number of
stress-related proteins significantly increased under planktonic growth in
comparison to aggregate growth. The upregulated proteins, identified by MALDI-TOF
mass spectrometry, were two isoforms of a protein belonging to the universal
stress family (UspA), a thioredoxin-disulfide reductase, the Campylobacter jejuni
orthologue transcriptional regulator (Cj1172c), and the CocE/NonD hydrolase. We
conclude that Sediminibaterium sp. C3 growth is stressed under planktonic
conditions and that aggregation induced by pyruvate protects the bacteria against
oxidative stress.
PMID- 25847232
TI - CyclinA2-Cyclin-dependent Kinase Regulates SAMHD1 Protein Phosphohydrolase
Domain.
AB - SAMHD1 is a nuclear deoxyribonucleoside triphosphate triphosphohydrolase that
contributes to the control of cellular deoxyribonucleoside triphosphate (dNTP)
pool sizes through dNTP hydrolysis and modulates the innate immune response to
viruses. CyclinA2-CDK1/2 phosphorylates SAMHD1 at Thr-592, but how this
modification controls SAMHD1 functions in proliferating cells is not known. Here,
we show that SAMHD1 levels remain relatively unchanged during the cell division
cycle in primary human T lymphocytes and in monocytic cell lines. Inactivation of
the bipartite cyclinA2-CDK-binding site in the SAMHD1 C terminus described herein
abolished SAMHD1 phosphorylation on Thr-592 during S and G2 phases thus
interfering with DNA replication and progression of cells through S phase. The
effects exerted by Thr-592 phosphorylation-defective SAMHD1 mutants were
associated with activation of DNA damage checkpoint and depletion of dNTP
concentrations to levels lower than those seen upon expression of wild type
SAMHD1 protein. These disruptive effects were relieved by either mutation of the
catalytic residues of the SAMHD1 phosphohydrolase domain or by a Thr-592
phosphomimetic mutation, thus linking the Thr-592 phosphorylation state to the
control of SAMHD1 dNTPase activity. Our findings support a model in which
phosphorylation of Thr-592 by cyclinA2-CDK down-modulates, but does not
inactivate, SAMHD1 dNTPase in S phase, thereby fine-tuning SAMHD1 control of dNTP
levels during DNA replication.
PMID- 25847233
TI - Hetero-oligomeric Complex between the G Protein-coupled Estrogen Receptor 1 and
the Plasma Membrane Ca2+-ATPase 4b.
AB - The new G protein-coupled estrogen receptor 1 (GPER/GPR30) plays important roles
in many organ systems. The plasma membrane Ca(2+)-ATPase (PMCA) is essential for
removal of cytoplasmic Ca(2+) and for shaping the time courses of Ca(2+)
dependent activities. Here, we show that PMCA and GPER/GPR30 physically interact
and functionally influence each other. In primary endothelial cells, GPER/GPR30
agonist G-1 decreases PMCA-mediated Ca(2+) extrusion by promoting PMCA tyrosine
phosphorylation. GPER/GPR30 overexpression decreases PMCA activity, and G-1
further potentiates this effect. GPER/GPR30 knockdown increases PMCA activity,
whereas PMCA knockdown substantially reduces GPER/GPR30-mediated phosphorylation
of the extracellular signal-related kinase (ERK1/2). GPER/GPR30 co
immunoprecipitates with PMCA with or without treatment with 17beta-estradiol,
thapsigargin, or G-1. Heterologously expressed GPER/GPR30 in HEK 293 cells co
localizes with PMCA4b, the main endothelial PMCA isoform. Endothelial cells
robustly express the PDZ post-synaptic density protein (PSD)-95, whose knockdown
reduces the association between GPER/GPR30 and PMCA. Additionally, the
association between PMCA4b and GPER/GPR30 is substantially reduced by truncation
of either or both of their C-terminal PDZ-binding motifs. Functionally,
inhibition of PMCA activity is significantly reduced by truncation of
GPER/GPR30's C-terminal PDZ-binding motif. These data strongly indicate that
GPER/GPR30 and PMCA4b form a hetero-oligomeric complex in part via the anchoring
action of PSD-95, in which they constitutively affect each other's function.
Activation of GPER/GPR30 further inhibits PMCA activity through tyrosine
phosphorylation of the pump. These interactions represent cross-talk between
Ca(2+) signaling and GPER/GPR30-mediated activities.
PMID- 25847234
TI - Localization and Function of Pals1-associated Tight Junction Protein in
Drosophila Is Regulated by Two Distinct Apical Complexes.
AB - The transmembrane protein Crumbs (Crb) and its intracellular adaptor protein
Pals1 (Stardust, Sdt in Drosophila) play a crucial role in the establishment and
maintenance of apical-basal polarity in epithelial cells in various organisms. In
contrast, the multiple PDZ domain-containing protein Pals1-associated tight
junction protein (PATJ), which has been described to form a complex with Crb/Sdt,
is not essential for apical basal polarity or for the stability of the Crb/Sdt
complex in the Drosophila epidermis. Here we show that, in the embryonic
epidermis, Sdt is essential for the correct subcellular localization of PATJ in
differentiated epithelial cells but not during cellularization. Consistently, the
L27 domain of PATJ is crucial for the correct localization and function of the
protein. Our data further indicate that the four PDZ domains of PATJ function, to
a large extent, in redundancy, regulating the function of the protein.
Interestingly, the PATJ-Sdt heterodimer is not only recruited to the apical cell
cell contacts by binding to Crb but depends on functional Bazooka (Baz). However,
biochemical experiments show that PATJ associates with both complexes, the Baz
Sdt and the Crb-Sdt complex, in the mature epithelium of the embryonic epidermis,
suggesting a role of these two complexes for the function of PATJ during the
development of Drosophila.
PMID- 25847235
TI - Fatty Acid-binding Proteins 1 and 2 Differentially Modulate the Activation of
Peroxisome Proliferator-activated Receptor alpha in a Ligand-selective Manner.
AB - Nuclear hormone receptors (NHRs) regulate the expression of proteins that control
aspects of reproduction, development and metabolism, and are major therapeutic
targets. However, NHRs are ubiquitous and participate in multiple physiological
processes. Drugs that act at NHRs are therefore commonly restricted by toxicity,
often at nontarget organs. For endogenous NHR ligands, intracellular lipid
binding proteins, including the fatty acid-binding proteins (FABPs), can
chaperone ligands to the nucleus and promote NHR activation. Drugs also bind
FABPs, raising the possibility that FABPs similarly regulate drug activity at the
NHRs. Here, we investigate the ability of FABP1 and FABP2 (intracellular lipid
binding proteins that are highly expressed in tissues involved in lipid
metabolism, including the liver and intestine) to influence drug-mediated
activation of the lipid regulator peroxisome proliferator-activated receptor
(PPAR) alpha. We show by quantitative fluorescence imaging and gene reporter
assays that drug binding to FABP1 and FABP2 promotes nuclear localization and
PPARalpha activation in a drug- and FABP-dependent manner. We further show that
nuclear accumulation of FABP1 and FABP2 is dependent on the presence of
PPARalpha. Nuclear accumulation of FABP on drug binding is driven largely by
reduced nuclear egress rather than an increased rate of nuclear entry. Importin
binding assays indicate that nuclear access occurs via an importin-independent
mechanism. Together, the data suggest that specific drug-FABP complexes can
interact with PPARalpha to effect nuclear accumulation of FABP and NHR
activation. Because FABPs are expressed in a regionally selective manner, this
may provide a means to tailor the patterns of NHR drug activation in a tissue
specific manner.
PMID- 25847236
TI - Cytokinetic Failure-induced Tetraploidy Develops into Aneuploidy, Triggering Skin
Aging in Phosphovimentin-deficient Mice.
AB - Tetraploidy, a state in which cells have doubled chromosomal sets, is observed in
~20% of solid tumors and is considered to frequently precede aneuploidy in
carcinogenesis. Tetraploidy is also detected during terminal differentiation and
represents a hallmark of aging. Most tetraploid cultured cells are arrested by
p53 stabilization. However, the fate of tetraploid cells in vivo remains largely
unknown. Here, we analyze the ability to repair wounds in the skin of
phosphovimentin-deficient (VIM(SA/SA)) mice. Early into wound healing,
subcutaneous fibroblasts failed to undergo cytokinesis, resulting in binucleate
tetraploidy. Accordingly, the mRNA level of p21 (a p53-responsive gene) was
elevated in a VIM(SA/SA)-specific manner. Disappearance of tetraploidy coincided
with an increase in aneuploidy. Thereafter, senescence-related markers were
significantly elevated in VIM(SA/SA) mice. Because our tetraploidy-prone mouse
model also exhibited subcutaneous fat loss at the age of 14 months, another
premature aging phenotype, our data suggest that following cytokinetic failure, a
subset of tetraploid cells enters a new cell cycle and develops into aneuploid
cells in vivo, which promote premature aging.
PMID- 25847237
TI - Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and
Th17 Differentiation and Promotes Tuberculosis Pathogenesis.
AB - Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient
pathogen and a major cause of death worldwide. Although various virulence factors
of M. tuberculosis have been identified, its pathogenesis remains incompletely
understood. TlyA is a virulence factor in several bacterial infections and is
evolutionarily conserved in many Gram-positive bacteria, but its function in M.
tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA
significantly contributes to the pathogenesis of M. tuberculosis. We show that a
TlyA mutant M. tuberculosis strain induces increased IL-12 and reduced IL-1beta
and IL-10 cytokine responses, which sharply contrasts with the immune responses
induced by wild type M. tuberculosis. Furthermore, compared with wild type M.
tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to
autophagy in macrophages. Consequently, animals infected with the TlyA mutant M.
tuberculosis organisms exhibited increased host-protective immune responses,
reduced bacillary load, and increased survival compared with animals infected
with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host
evasion factor, thereby contributing to its virulence.
PMID- 25847238
TI - Hepatic serum amyloid A1 aggravates T cell-mediated hepatitis by inducing
chemokines via Toll-like receptor 2 in mice.
AB - Serum amyloid A is a proinflammatory molecule that induces leukocyte infiltration
and promotes neutrophil adhesion to endothelial cells under inflammatory
conditions. The aim of this study was to examine whether Saa1 aggravates T cell
mediated hepatitis by inducing chemokines in a liver-specific, Saa1
overexpressing, transgenic (TG) mouse model. We generated TG mice in which Saa1
was overexpressed specifically in liver tissue. The chemokines monocyte
chemotactic protein 1 (MCP1), MIP1alpha, MIP1beta, interferon gamma-induced
protein 10 (IP-10), and eotaxin were induced in Saa1 TG mice. After concanavalin
A treatment, Saa1 expression was higher in Saa1 TG mice than in WT mice. More
severe liver injury, increased hepatocyte apoptosis, and higher levels of hepatic
enzymes were observed in Saa1 TG mice than in WT mice. Liver infiltration of
CD4(+) T cells and macrophages increased after inducing hepatitis. Activation of
T cells was higher in Saa1 TG mice than in WT mice, and the populations of Th17
cells and regulatory T cells were altered by overexpressing Saa1 in TG mice.
Secretion of various cytokines, such as interferon gamma, tumor necrosis factor
alpha, and interleukin 6, increased in Saa1 TG mice. Injecting a Toll-like
receptor 2 (TLR2) antagonist in vivo inhibited chemokine expression and
IkappaBalpha phosphorylation and showed that the induction of chemokines by Saa1
was dependent on TLR2. Hepatic Saa1 accelerated T cell-mediated hepatitis by
inducing chemokine production and activating T cells by TLR2. Therefore, Saa1
might be a novel inflammatory factor that acts as a chemokine modulator in
hepatitis.
PMID- 25847240
TI - Abscisic acid transport in human erythrocytes.
AB - Abscisic acid (ABA) is a plant hormone involved in the response to environmental
stress. Recently, ABA has been shown to be present and active also in mammals,
where it stimulates the functional activity of innate immune cells, of
mesenchymal and hemopoietic stem cells, and insulin-releasing pancreatic beta
cells. LANCL2, the ABA receptor in mammalian cells, is a peripheral membrane
protein that localizes at the intracellular side of the plasma membrane. Here we
investigated the mechanism enabling ABA transport across the plasmamembrane of
human red blood cells (RBC). Both influx and efflux of [(3)H]ABA occur across
intact RBC, as detected by radiometric and chromatographic methods. ABA binds
specifically to Band 3 (the RBC anion transporter), as determined by labeling of
RBC membranes with biotinylated ABA. Proteoliposomes reconstituted with human
purified Band 3 transport [(3)H]ABA and [(35)S]sulfate, and ABA transport is
sensitive to the specific Band 3 inhibitor 4,4'-diisothiocyanostilbene-2,2'
disulfonic acid. Once inside RBC, ABA stimulates ATP release through the LANCL2
mediated activation of adenylate cyclase. As ATP released from RBC is known to
exert a vasodilator response, these results suggest a role for plasma ABA in the
regulation of vascular tone.
PMID- 25847239
TI - PRMT1 Is a Novel Regulator of Epithelial-Mesenchymal-Transition in Non-small Cell
Lung Cancer.
AB - Protein arginine methyl transferase 1 (PRMT1) was shown to be up-regulated in
cancers and important for cancer cell proliferation. However, the role of PRMT1
in lung cancer progression and metastasis remains incompletely understood. In the
present study, we show that PRMT1 is an important regulator of epithelial
mesenchymal transition (EMT), cancer cell migration, and invasion, which are
essential processes during cancer progression, and metastasis. Additionally, we
have identified Twist1, a basic helix-loop-helix transcription factor and a well
known E-cadherin repressor, as a novel PRMT1 substrate. Taken together, we show
that PRMT1 is a novel regulator of EMT and arginine 34 (Arg-34) methylation of
Twist1 as a unique "methyl arginine mark" for active E-cadherin repression.
Therefore, targeting PRMT1-mediated Twist1 methylation might represent a novel
strategy for developing new anti-invasive/anti-metastatic drugs. Moreover,
methylated Twist1 (Arg-34), as such, could also emerge as a potential important
biomarker for lung cancer.
PMID- 25847241
TI - Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA
Expression.
AB - Interleukin 31 receptor alpha (IL-31RA) is a novel Type I cytokine receptor that
pairs with oncostatin M receptor to mediate IL-31 signaling. Binding of IL-31 to
its receptor results in the phosphorylation and activation of STATs, MAPK, and
JNK signaling pathways. IL-31 plays a pathogenic role in tissue inflammation,
particularly in allergic diseases. Recent studies demonstrate IL-31RA expression
and signaling in non-hematopoietic cells, but this receptor is poorly studied in
immune cells. Macrophages are key immune-effector cells that play a critical role
in Th2-cytokine-mediated allergic diseases. Here, we demonstrate that Th2
cytokines IL-4 and IL-13 are capable of up-regulating IL-31RA expression on both
peritoneal and bone marrow-derived macrophages from mice. Our data also
demonstrate that IL-4Ralpha-driven IL-31RA expression is STAT6 dependent in
macrophages. Notably, the inflammation-associated genes Fizz1 and serum amyloid A
(SAA) are significantly up-regulated in M2 macrophages stimulated with IL-31, but
not in IL-4 receptor-deficient macrophages. Furthermore, the absence of Type II
IL-4 receptor signaling is sufficient to attenuate the expression of IL-31RA in
vivo during allergic asthma induced by soluble egg antigen, which may suggest a
role for IL-31 signaling in Th2 cytokine-driven inflammation and allergic
responses. Our study reveals an important counter-regulatory role between Th2
cytokine and IL-31 signaling involved in allergic diseases.
PMID- 25847242
TI - X-ray and Cryo-electron Microscopy Structures of Monalysin Pore-forming Toxin
Reveal Multimerization of the Pro-form.
AB - beta-Barrel pore-forming toxins (beta-PFT), a large family of bacterial toxins,
are generally secreted as water-soluble monomers and can form oligomeric pores in
membranes following proteolytic cleavage and interaction with cell surface
receptors. Monalysin has been recently identified as a beta-PFT that contributes
to the virulence of Pseudomonas entomophila against Drosophila. It is secreted as
a pro-protein that becomes active upon cleavage. Here we report the crystal and
cryo-electron microscopy structure of the pro-form of Monalysin as well as the
crystal structures of the cleaved form and of an inactive mutant lacking the
membrane-spanning region. The overall structure of Monalysin displays an
elongated shape, which resembles those of beta-pore-forming toxins, such as
Aerolysin, but is devoid of a receptor-binding domain. X-ray crystallography,
cryo-electron microscopy, and light-scattering studies show that pro-Monalysin
forms a stable doughnut-like 18-mer complex composed of two disk-shaped nonamers
held together by N-terminal swapping of the pro-peptides. This observation is in
contrast with the monomeric pro-form of the other beta-PFTs that are receptor
dependent for membrane interaction. The membrane-spanning region of pro-Monalysin
is fully buried in the center of the doughnut, suggesting that upon cleavage of
pro-peptides, the two disk-shaped nonamers can, and have to, dissociate to leave
the transmembrane segments free to deploy and lead to pore formation. In contrast
with other toxins, the delivery of 18 subunits at once, nearby the cell surface,
may be used to bypass the requirement of receptor-dependent concentration to
reach the threshold for oligomerization into the pore-forming complex.
PMID- 25847243
TI - Baicalin inhibits the lethality of ricin in mice by inducing protein
oligomerization.
AB - Toxic ribosome-inactivating proteins abolish cell viability by inhibiting protein
synthesis. Ricin, a member of these lethal proteins, is a potential bioterrorism
agent. Despite the grave challenge posed by these toxins to public health, post
exposure treatment for intoxication caused by these agents currently is
unavailable. In this study, we report the identification of baicalin extracted
from Chinese herbal medicine as a compound capable of inhibiting the activity of
ricin. More importantly, post-exposure treatment with baicalin significantly
increased the survival of mice poisoned by ricin. We determined the mechanism of
action of baicalin by solving the crystal structure of its complex with the A
chain of ricin (RTA) at 2.2 A resolution, which revealed that baicalin interacts
with two RTA molecules at a novel binding site by hydrogen bond networks and
electrostatic force interactions, suggesting its role as molecular glue of the
RTA. Further biochemical and biophysical analyses validated the amino acids
directly involved in binding the inhibitor, which is consistent with the
hypothesis that baicalin exerts its inhibitory effects by inducing RTA to form
oligomers in solution, a mechanism that is distinctly different from previously
reported inhibitors. This work offers promising leads for the development of
therapeutics against ricin and probably other ribosome-inactivating proteins.
PMID- 25847244
TI - Histone Chaperone HIRA in Regulation of Transcription Factor RUNX1.
AB - RUNX1 (Runt-related transcription factor 1) is indispensable for the generation
of hemogenic endothelium. However, the regulation of RUNX1 during this
developmental process is poorly understood. We investigated the role of the
histone chaperone HIRA (histone cell cycle regulation-defective homolog A) from
this perspective and report that HIRA significantly contributes toward the
regulation of RUNX1 in the transition of differentiating mouse embryonic stem
cells from hemogenic to hematopoietic stage. Direct interaction of HIRA and RUNX1
activates the downstream targets of RUNX1 implicated in generation of
hematopoietic stem cells. At the molecular level, HIRA-mediated incorporation of
histone H3.3 variant within the Runx1 +24 mouse conserved noncoding element is
essential for the expression of Runx1 during endothelial to hematopoietic
transition. An inactive chromatin at the intronic enhancer of Runx1 in absence of
HIRA significantly repressed the transition of cells from hemogenic to
hematopoietic fate. We expect that the HIRA-RUNX1 axis might open up a novel
approach in understanding leukemogenesis in future.
PMID- 25847245
TI - Two duplicated genes DDI2 and DDI3 in budding yeast encode a cyanamide hydratase
and are induced by cyanamide.
AB - Two DNA damage-inducible genes in Saccharomyces cerevisiae, DDI2 and DDI3, are
identical and encode putative HD domain-containing proteins, whose functions are
currently unknown. Because Ddi2/3 also shows limited homology to a fungal
cyanamide hydratase that converts cyanamide to urea, we tested the enzymatic
activity of recombinant Ddi2. To this end, we developed a novel enzymatic assay
and determined that the Km value of the recombinant Ddi2/3 for cyanamide is 17.3
+/- 0.05 mm, and its activity requires conserved residues in the HD domain.
Unlike most other DNA damage-inducible genes, DDI2/3 is only induced by a
specific set of alkylating agents and surprisingly is strongly induced by
cyanamide. To characterize the biological function of DDI2/3, we sequentially
deleted both DDI genes and found that the double mutant was unable to metabolize
cyanamide and became much more sensitive to growth inhibition by cyanamide,
suggesting that the DDI2/3 genes protect host cells from cyanamide toxicity.
Despite the physiological relevance of the cyanamide induction, DDI2/3 is not
involved in its own transcriptional regulation. The significance of cyanamide
hydratase activity and its induced expression is discussed.
PMID- 25847246
TI - Association of MMP7 -181A->G Promoter Polymorphism with Gastric Cancer Risk:
INFLUENCE OF NICOTINE IN DIFFERENTIAL ALLELE-SPECIFIC TRANSCRIPTION VIA INCREASED
PHOSPHORYLATION OF cAMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB).
AB - Elevated expression of matrix metalloproteinase7 (MMP7) has been demonstrated to
play a pivotal role in cancer invasion. The -181A->G (rs11568818) polymorphism in
the MMP7 promoter modulates gene expression and possibly affects cancer
progression. Here, we evaluated the impact of -181A->G polymorphism on MMP7
promoter activity and its association with gastric cancer risk in eastern Indian
case-control cohorts (n = 520). The GG genotype as compared with the AA genotype
was predisposed (p = 0.02; odds ratio = 1.9, 95% confidence interval = 1.1-3.3)
to gastric cancer risk. Stratification analysis showed that tobacco addiction
enhanced gastric cancer risk in GG subjects when compared with AA subjects (p =
0.03, odds ratio = 2.46, and 95% confidence interval = 1.07-5.68). Meta-analysis
revealed that tobacco enhanced the risk for cancer more markedly in AG and GG
carriers. Activity and expression of MMP7 were significantly higher in GG than in
AA carriers. In support, MMP7 promoter-reporter assays showed greater
transcriptional activity toward A to G transition under basal/nicotine
induced/cAMP-response element-binding protein (CREB) overexpressed conditions in
gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco)
treatment significantly up-regulated MMP7 expression due to enhanced CREB
phosphorylation followed by its nuclear translocation in gastric adenocarcinoma
cells. Furthermore, chromatin immunoprecipitation experiments revealed higher
binding of phosphorylated CREB with the -181G than the -181A allele. Altogether,
specific binding of phosphorylated CREB to the G allele-carrying promoter
enhances MMP7 gene expression that is further augmented by nicotine due to
increased CREB phosphorylation and thereby increases the risk for gastric cancer.
PMID- 25847247
TI - Crucial genes and pathways in chicken germ stem cell differentiation.
AB - Male germ cell differentiation is a subtle and complex regulatory process.
Currently, its regulatory mechanism is still not fully understood. In our
experiment, we performed the first comprehensive genome and transcriptome-wide
analyses of the crucial genes and signaling pathways in three kinds of crucial
cells (embryonic stem cells, primordial germ cell, and spermatogonial stem cells)
that are associated with the male germ cell differentiation. We identified
thousands of differentially expressed genes in this process, and from these we
chose 173 candidate genes, of which 98 genes were involved in cell
differentiation, 19 were involved in the metabolic process, and 56 were involved
in the differentiation and metabolic processes, like GAL9, AMH, PLK1, and PSMD7
and so on. In addition, we found that 18 key signaling pathways were involved
mainly in cell proliferation, differentiation, and signal transduction processes
like TGF-beta, Notch, and Jak-STAT. Further exploration found that the candidate
gene expression patterns were the same between in vitro induction experiments and
transcriptome results. Our results yield clues to the mechanistic basis of male
germ cell differentiation and provide an important reference for further studies.
PMID- 25847248
TI - Crystal Structure of the Human Pol alpha B Subunit in Complex with the C-terminal
Domain of the Catalytic Subunit.
AB - In eukaryotic DNA replication, short RNA-DNA hybrid primers synthesized by
primase-DNA polymerase alpha (Prim-Pol alpha) are needed to start DNA replication
by the replicative DNA polymerases, Pol delta and Pol epsilon. The C terminus of
the Pol alpha catalytic subunit (p180C) in complex with the B subunit (p70)
regulates the RNA priming and DNA polymerizing activities of Prim-Pol alpha. It
tethers Pol alpha and primase, facilitating RNA primer handover from primase to
Pol alpha. To understand these regulatory mechanisms and to reveal the details of
human Pol alpha organization, we determined the crystal structure of p70 in
complex with p180C. The structured portion of p70 includes a phosphodiesterase
(PDE) domain and an oligonucleotide/oligosaccharide binding (OB) domain. The N
terminal domain and the linker connecting it to the PDE domain are disordered in
the reported crystal structure. The p180C adopts an elongated asymmetric saddle
shape, with a three-helix bundle in the middle and zinc-binding modules (Zn1 and
Zn2) on each side. The extensive p180C-p70 interactions involve 20 hydrogen bonds
and a number of hydrophobic interactions resulting in an extended buried surface
of 4080 A(2). Importantly, in the structure of the p180C-p70 complex with full
length p70, the residues from the N-terminal to the OB domain contribute to
interactions with p180C. The comparative structural analysis revealed both the
conserved features and the differences between the human and yeast Pol alpha
complexes.
PMID- 25847249
TI - In Silico Modeling-based Identification of Glucose Transporter 4 (GLUT4)
selective Inhibitors for Cancer Therapy.
AB - Tumor cells rely on elevated glucose consumption and metabolism for survival and
proliferation. Glucose transporters mediating glucose entry are key proximal rate
limiting checkpoints. Unlike GLUT1 that is highly expressed in cancer and more
ubiquitously expressed in normal tissues, GLUT4 exhibits more limited normal
expression profiles. We have previously determined that insulin-responsive GLUT4
is constitutively localized on the plasma membrane of myeloma cells.
Consequently, suppression of GLUT4 or inhibition of glucose transport with the
HIV protease inhibitor ritonavir elicited growth arrest and/or apoptosis in
multiple myeloma. GLUT4 inhibition also caused sensitization to metformin in
multiple myeloma and chronic lymphocytic leukemia and a number of solid tumors
suggesting the broader therapeutic utility of targeting GLUT4. This study sought
to identify selective inhibitors of GLUT4 to develop a more potent cancer
chemotherapeutic with fewer potential off-target effects. Recently, the crystal
structure of GLUT1 in an inward open conformation was reported. Although this is
an important achievement, a full understanding of the structural biology of
facilitative glucose transport remains elusive. To date, there is no three
dimensional structure for GLUT4. We have generated a homology model for GLUT4
that we utilized to screen for drug-like compounds from a library of 18 million
compounds. Despite 68% homology between GLUT1 and GLUT4, our virtual screen
identified two potent compounds that were shown to target GLUT4 preferentially
over GLUT1 and block glucose transport. Our results strongly bolster the utility
of developing GLUT4-selective inhibitors as anti-cancer therapeutics.
PMID- 25847250
TI - Formation and decay of the arrestin.rhodopsin complex in native disc membranes.
AB - In the G protein-coupled receptor rhodopsin, light-induced cis/trans
isomerization of the retinal ligand triggers a series of distinct receptor states
culminating in the active Metarhodopsin II (Meta II) state, which binds and
activates the G protein transducin (Gt). Long before Meta II decays into the
aporeceptor opsin and free all-trans-retinal, its signaling is quenched by
receptor phosphorylation and binding of the protein arrestin-1, which blocks
further access of Gt to Meta II. Although recent crystal structures of arrestin
indicate how it might look in a precomplex with the phosphorylated receptor, the
transition into the high affinity complex is not understood. Here we applied
Fourier transform infrared spectroscopy to monitor the interaction of arrestin-1
and phosphorylated rhodopsin in native disc membranes. By isolating the unique
infrared signature of arrestin binding, we directly observed the structural
alterations in both reaction partners. In the high affinity complex, rhodopsin
adopts a structure similar to Gt-bound Meta II. In arrestin, a modest loss of
beta-sheet structure indicates an increase in flexibility but is inconsistent
with a large scale structural change. During Meta II decay, the arrestin
rhodopsin stoichiometry shifts from 1:1 to 1:2. Arrestin stabilizes half of the
receptor population in a specific Meta II protein conformation, whereas the other
half decays to inactive opsin. Altogether these results illustrate the distinct
binding modes used by arrestin to interact with different functional forms of the
receptor.
PMID- 25847252
TI - Ex vivo evaluation of the effect of photodynamic therapy on skin scars and striae
distensae.
AB - BACKGROUND: Skin scars and striae distensae (SD) are common dermal disorders with
ill-defined treatment options. There is emerging clinical evidence for use of
photodynamic therapy (PDT) in treating skin fibrosis. Therefore, the aim here was
to investigate the effect of PDT on skin scars and SD in an ex vivo model of
human skin scarring. METHODS: Photodynamic therapy, with 5ALA or MALA in addition
to illumination with 40 J/cm(2) of red light, was applied to striae alba, fine
line, hypertrophic and keloid scars ex vivo (n = 18). General morphology was
assessed by H&E, Herovici's and Weigert's differential staining. Apoptosis,
proliferation, metalloproteinase 3 and tropoelastin expression were quantified
immunohistochemically, and differential gene expression of proliferating cell
nuclear antigen (PCNA), collagen (COL) type I and type III, matrix
metalloproteinase 3 (MMP3) and tropoelastin (ELN) was assessed by real-time
quantitative reverse transcription polymerase chain reaction. RESULTS: Apoptosis
increased, which correlated with decreased proliferation and PCNA gene
expression. Post-PDT, matrix components were found to be re-organised in both
hypertrophic and keloid scars. COLI and COLIII gene expression levels decreased,
whilst MMP3 and ELN increased significantly post-PDT compared to normal skin and
untreated controls (P < 0.05). However, no significant difference between 5ALA
and MALA-PDT treatments was observed. CONCLUSION: Using our unique ex vivo model,
we show for the first time morphological and cellular effect of application of
PDT, which correlates with the degree and severity of dermal fibrosis. In view of
this, PDT may be ideal in targeting treatment of abnormal skin scarring.
PMID- 25847253
TI - Epigallocatechin gallate stimulates the neuroreactive salivary secretomotor
system in autoimmune sialadenitis of MRL-Fas(lpr) mice via activation of cAMP
dependent protein kinase A and inactivation of nuclear factor kappaB.
AB - The water channel aquaporin 5 (AQP5) plays a crucial role in regulating salivary
flow rates. Xerostomia is often observed in patients with Sjogren's syndrome, and
this is attributed to reduced AQP5 expression in the salivary glands. Recently,
anti-type 3 muscarinic cholinergic receptors (M3R) autoantibodies and nuclear
factor kappaB (NF-kappaB) have been found to be negative regulators of AQP5
expression in the salivary gland. Anti-M3R autoantibodies desensitize M3R to
salivary secretagogues in Sjogren's syndrome, while activated NF-kappaB
translocates to nuclei and binds to the AQP5 gene promoter, resulting in the
suppression of AQP5 expression. We previously documented that epigallocatechin
gallate (EGCG), which is a robust antioxidant contained in green tea, ameliorates
oxidative stress-induced tissue damage to the salivary glands of MRL/MpJ-lpr/lpr
(MRL-Fas(lpr)) mice, which are widely used as a model of Sjogren's syndrome.
Reactive oxygen species (ROS) can activate NF-kappaB and inactivate protein
kinase A (PKA), which is a key driver of AQP5 expression. In this study, we
examined the effects of administering EGCG to MRL-Fas(lpr) mice with autoimmune
sialadenitis on the levels of AQP5, activated NF-kappaB p65 subunit, activated
PKA, activated c-Jun N-terminal kinase (JNK) (an activator of NF-kappaB),
inhibitor kappaB (IkappaB) and histone deacetylase 1 (HDAC1) (an inhibitor of NF
kappaB). In EGCG-treated mice, intense aster-like immunostaining for AQP5 was
observed on the apical plasma membranes (APMs) of submandibular gland acinar
cells. Likewise, PKA, IkappaB and HDAC1 were highly expressed in salivary gland
tissues, whereas the expression of JNK and NF-kappaB p65 was negligible. Rank
correlation and partial correlation analyses revealed that treatment with EGCG
upregulated AQP5 expression on the APM of acinar cells through activation of PKA
and inactivation of NF-kappaB, while IkappaB and HDAC1 played a pivotal role in
the induction of AQP5 expression by PKA. Our study indicates that EGCG may have
therapeutic potential for Sjogren's syndrome patients.
PMID- 25847251
TI - Diaminopimelic Acid Amidation in Corynebacteriales: NEW INSIGHTS INTO THE ROLE OF
LtsA IN PEPTIDOGLYCAN MODIFICATION.
AB - A gene named ltsA was earlier identified in Rhodococcus and Corynebacterium
species while screening for mutations leading to increased cell susceptibility to
lysozyme. The encoded protein belonged to a huge family of glutamine
amidotransferases whose members catalyze amide nitrogen transfer from glutamine
to various specific acceptor substrates. We here describe detailed physiological
and biochemical investigations demonstrating the specific role of LtsA protein
from Corynebacterium glutamicum (LtsACg) in the modification by amidation of cell
wall peptidoglycan diaminopimelic acid (DAP) residues. A morphologically altered
but viable DeltaltsA mutant was generated, which displays a high susceptibility
to lysozyme and beta-lactam antibiotics. Analysis of its peptidoglycan structure
revealed a total loss of DAP amidation, a modification that was found in 80% of
DAP residues in the wild-type polymer. The cell peptidoglycan content and cross
linking were otherwise not modified in the mutant. Heterologous expression of
LtsACg in Escherichia coli yielded a massive and toxic incorporation of amidated
DAP into the peptidoglycan that ultimately led to cell lysis. In vitro assays
confirmed the amidotransferase activity of LtsACg and showed that this enzyme
used the peptidoglycan lipid intermediates I and II but not, or only marginally,
the UDP-MurNAc pentapeptide nucleotide precursor as acceptor substrates. As is
generally the case for glutamine amidotransferases, either glutamine or NH4(+)
could serve as the donor substrate for LtsACg. The enzyme did not amidate
tripeptide- and tetrapeptide-truncated versions of lipid I, indicating a strict
specificity for a pentapeptide chain length.
PMID- 25847254
TI - Effect of the Acidic Dental Resin Monomer 10-methacryloyloxydecyl Dihydrogen
Phosphate on Odontoblastic Differentiation of Human Dental Pulp Cells.
AB - Although 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) is frequently used
as an acidic resin monomer in dental adhesives, its effect on dental pulp cells
(DPCs) has been rarely reported. The purpose of this study was to examine the
effects of 10-MDP on the inflammatory response and odontoblastic differentiation
of DPCs at minimally toxic concentrations. We found that 10-MDP caused the
release of inflammatory cytokines including NO, PGE2, iNOS, COX-2, TNF-alpha, IL
1beta, IL-6 and IL-8 in a concentration-dependent manner. In addition, 10-MDP
reduced alkaline phosphatase activity, mineralization nodule formation and mRNA
expression of odontoblastic differentiation markers such as dentin
sialophosphoprotein, dentin matrix protein-1, osterix and Runx2 in a
concentration-dependent manner with low toxicity. In addition, 10-MDP induced
activation of nuclear factor-E2-related factor 2 (Nrf2) and its target gene,
haeme oxygenase-1 (HO-1). We evaluated whether the effect of 10-MDP was related
to the induction of HO-1 and found that treatment with a selective inhibitor of
HO-1 reversed the production of 10-MDP-mediated pro-inflammatory cytokines and
the inhibition of differentiation markers. Pre-treatment with either a GSH
synthesis inhibitor or antioxidants blocked 10-MDP-induced mitogen-activated
protein kinases (MAPKs), Nrf2 and NF-kappaB pathways. Taken together, the results
of this study showed that minimally toxic concentrations of 10-MDP promoted an
inflammatory response and suppressed odontoblastic differentiation of DPCs by
activating Nrf2-mediated HO-1 induction through MAPK and NF-kappaB signalling.
PMID- 25847260
TI - Inhibition of expression of hepatitis C virus 1b genotype core and NS4B genes in
HepG2 cells using artificial microRNAs.
AB - The present study aimed to evaluate the silencing effect of artificial microRNAs
(amiRNAs) against the hepatitis C virus (HCV) 1b (HCV1b) genotype core (C) and
non-structural protein 4B (NS4B) genes. pDsRed-monomer-Core and pDsRed-monomer
NS4B plasmids, containing the target genes were constructed. A total of eight
artificial micro RNA (amiRNA)-expressing plasmids, namely, pmiRE-C-mi1 to -mi4
and pmiRE-NS4B-mi1 to -mi4, were designed and constructed to interfere with
various sites of the core and NS4B genes, and the amiRNA interfering plasmid and
the corresponding target gene-expressing plasmid were co-transfected into HepG2
cells. At 48 h after transfection, HCV core and NS4B gene expression levels were
detected using fluorescence microscopy, flow cytometry, reverse transcription
quantitative polymerase chain reaction and western blot analysis. Fluorescence
microscopy revealed that the target gene-transfected cells expressed red
fluorescent protein, whereas the interfering plasmid-transfected cells exhibited
expression of green fluorescent protein. The percentage of red fluorescent
proteins and mean fluorescence intensity, as well as protein expression levels of
the core and NS4B genes within the cells, which were co-transfected by the amiRNA
interfering plasmid and the target gene, were significantly decreased. The
results of the present study confirmed that amiRNAs may effectively and
specifically inhibit the expression of HCV1b core and NS4B genes in HepG2 cells,
potentially providing a novel therapeutic strategy for the treatment of HCV.
PMID- 25847261
TI - A type of novel fluorescent magnetic carbon quantum dots for cells imaging and
detection.
AB - A new type of multifunctional fluorescent magnetic carbon quantum dots
SPIO@CQDs(n) ([superparamagnetic iron oxide nanoparticles (SPIO), carbon quantum
dots, (CQDs)]) with magnetic and fluorescence properties was designed and
prepared through layer-by-layer self-assembly method. The as-synthesized
SPIO@CQDs(n) exhibited different emission colors including blue, green, and red
when they were excited at different excitation wavelengths, and its fluorescent
intensity increased as the increase of CQD layer (n). SPIO@CQDs(n) with quite low
toxicity could mark cytoplasm with fluorescence by means of nonimmune markers.
The mixture sample of liver cells L02 and hepatoma carcinoma cells HepG2 was
taken as an example, and HepG2 cells were successfully separated and detected
effectively by SPIO@CQDs(n), with a separation rate of 90.31%. Importantly, the
designed and prepared SPIO@CQDs( n ) are certified to be wonderful biological
imaging and magnetic separation regents.
PMID- 25847262
TI - Diagnosis of congenital Trypanosoma cruzi infection: A serologic test using Shed
Acute Phase Antigen (SAPA) in mother-child binomial samples.
AB - Chagas congenital infection is an important health problem in endemic and non
endemic areas in which Trypanosoma cruzi-infected women can transmit the parasite
to their offspring. In this study, we evaluated the antibody levels against the
T. cruzi Shed Acute Phase Antigen (SAPA) in 91 binomial samples of seropositive
pregnant women and their infected and non-infected children by ELISA. In 70
children without congenital T. cruzi transmission, the titers of anti-SAPA
antibodies were lower than those of their seropositive mothers. In contrast,
90.5% of 21 congenitally infected children, at around 1 month of age, showed
higher anti-SAPA antibody levels than their mothers. Subtracting the SAPA-ELISA
mother OD value to the SAPA-ELISA child OD allowed efficient detection of most T.
cruzi congenitally infected children immediately after birth, when total anti
parasite antibodies transferred during pregnancy are still present in all
children born to seropositive women. A positive correlation was observed between
parasitemia levels in mothers and infants evaluated by quantitative DNA
amplification and anti-SAPA antibody titers by ELISA. As SAPA serology has proved
to be very efficient to detect T. cruzi infection in mother-child binomial
samples, it could be of extreme help for early diagnosis of newborns, in
maternities and hospitals where DNA amplification is not available. This prompt
diagnosis may prevent drop out of the long-term follow-up for future diagnosis
and may ensure early trypanocidal treatment, which has proved to be efficient to
cure infants with congenital Chagas disease.
PMID- 25847263
TI - When private actors matter: Information-sharing network and surveillance of
Highly Pathogenic Avian Influenza in Vietnam.
AB - The effectiveness of animal health surveillance systems depends on their capacity
to gather sanitary information from the animal production sector. In order to
assess this capacity we analyzed the flow of sanitary information regarding
Highly Pathogenic Avian Influenza (HPAI) suspicions in poultry in Vietnam.
Participatory methods were applied to assess the type of actors and likelihood of
information sharing between actors in case of HPAI suspicion in poultry. While
the reporting of HPAI suspicions is mandatory, private actors had more access to
information than public actors. Actors of the upstream sector (medicine and feed
sellers) played a key role in the diffusion of information. The central role of
these actors and the influence of the information flow on the adoption by poultry
production stakeholders of behaviors limiting (e.g. prevention measures) or
promoting disease transmission (e.g. increased animal movements) should be
accounted for in the design of surveillance and control programs.
PMID- 25847264
TI - Noninvasive measurement of aristolochic acid-DNA adducts in urine samples from
aristolochic acid-treated rats by liquid chromatography coupled tandem mass
spectrometry: evidence for DNA repair by nucleotide-excision repair mechanisms.
AB - Nephrotoxic aristolochic acids (AAs) form covalently bonded DNA adducts upon
metabolic activation. In this work, a non-invasive approach to detect AAs
exposure by quantifying urinary excreted DNA-AA adducts is presented. The
developed method entails solid-phase extraction (SPE) enrichment of the urine
excreted DNA-AAs adducts, addition of internal standard, and quantification by
liquid chromatography coupled tandem mass spectrometric (LC-MS/MS) analysis.
Quantitative analysis revealed 7-(deoxyadenosine-N(6)-yl)-aristolactam II and 7
(deoxyguanosine-N(2)-yl)-aristolactam I that were previously detected as major
DNA-AA adducts in different organs of AA-dosed rats, were detected as the major
urine excreted adducts. Lower levels of 7-(deoxyadenosine-N(6)-yl)-aristolactam I
and 7-(deoxyguanosine-N(2)-yl)-aristolactam II were also detected in the
collected urine samples. The identities of the detected urinary DNA-AA adducts
were confirmed by comparing chromatographic retention time with synthetic
standards, by high-accuracy MS, and MS/MS analyses. LC-MS/MS analysis of the
urine samples collected from the AAs-dosed rats demonstrated a time-dependent
decrease in the urinary adduct levels, indicating the urinary DNA-AA adduct
levels were reflective of the tissue adduct levels. It is expected that the
developed approach of detecting urinary DNA-AA adducts will facilitate further
carcinogenesis investigations of AAs.
PMID- 25847266
TI - Optimization of the Divergent method for genotyping single nucleotide variations
using SYBR Green-based single-tube real-time PCR.
AB - A novel technique, called Divergent, for single-tube real-time PCR genotyping of
point mutations without the use of fluorescently labeled probes has recently been
reported. This novel PCR technique utilizes a set of four primers and a
particular denaturation temperature for simultaneously amplifying two different
amplicons which extend in opposite directions from the point mutation. The two
amplicons can readily be detected using the melt curve analysis downstream to a
closed-tube real-time PCR. In the present study, some critical aspects of the
original method were specifically addressed to further implement the technique
for genotyping the DNM1 c.G767T mutation responsible for exercise-induced
collapse in Labrador retriever dogs. The improved Divergent assay was easily set
up using a standard two-step real-time PCR protocol. The melting temperature
difference between the mutated and the wild-type amplicons was approximately 5
degrees C which could be promptly detected by all the thermal cyclers. The
upgraded assay yielded accurate results with 157pg of genomic DNA per reaction.
This optimized technique represents a flexible and inexpensive alternative to the
minor grove binder fluorescently labeled method and to high resolution melt
analysis for high-throughput, robust and cheap genotyping of single nucleotide
variations.
PMID- 25847265
TI - Inherited variability in a master regulator polymorphism (rs4846126) associates
with survival in 5-FU treated colorectal cancer patients.
AB - BACKGROUND: Treatment with 5-fluorouracil (5-FU) is known to improve survival in
many cancers including colorectal cancer. Response to the treatment, overall
survival and recurrence show inter-individual variation. METHODS: In this study
we employed a strategy to search eQTL variants influencing the expression of a
large number of genes. We identified four single nucleotide polymorphisms,
defined as master regulators of transcription, and genotyped them in a set of 218
colorectal cancer patients undergoing adjuvant 5-FU based therapy. RESULTS: Our
results showed that the minor allele variant of the rs4846126 polymorphism was
associated with poor overall and progression-free survival. Patients that were
homozygous for the variant allele showed an over two fold increased risk of death
(HR 2.20 95%CI 1.05-4.60) and progression (HR 2.88, 95% 1.47-5.63). The
integration of external information from publicly available gene expression
repositories suggested that the rs4846126 polymorphism deserves further
investigation. This variant potentially regulates the gene expression of 273
genes with some of them possibly associated to the patient's response to 5-FU
treatment or colorectal cancer. CONCLUSIONS: Present results show that mining of
public data repositories in combination with own data can be a fruitful approach
to identify markers that affect therapy outcome. In particular, a genetic screen
of master regulators may help in order to search for the polymorphisms involved
in treatment response in cancer patients.
PMID- 25847267
TI - Impact of abasic site orientation within nucleosomes on human APE1 endonuclease
activity.
AB - Glycosylases responsible for recognizing DNA lesions and initiating Base Excision
Repair (BER) are impeded by the presence of histones, which are essential for
compaction of the genetic material in the nucleus. Abasic sites are an abundant
mutagenic lesion in the DNA, arising spontaneously and as the product of
glycosylase activity, making it a common intermediate in BER. The
apurinic/apyrimidinic endonuclease 1 (APE1) recognizes abasic sites and cleaves
the DNA backbone adjacent to the lesion, creating the single-strand break
essential for the subsequent steps of BER. In this study the endonuclease
activity of human APE1 was measured on reconstituted nucleosome core particles
(NCPs) with DNA containing enzymatically created abasic sites (AP) or the abasic
site analog tetrahydrofuran (TF) at different rotational positions relative to
the histone core surface. The presence of histones on the DNA reduced APE1
activity overall, and the magnitude was greatly influenced by differences in
orientation of the lesions along the DNA gyre relative to the histone core.
Abasic moieties oriented with their phosphate backbones adjacent to the
underlying histones (In) were cleaved less efficiently than those oriented away
from the histone core (Out) or between the In and Out orientations (Mid). The
impact on APE1 at each orientation was very similar between the AP and TF
lesions, highlighting the dependability of the TF abasic analog in APE1 activity
measurements in nucleosomes. Measurement of APE1 binding to the NCP substrates
reveals a substantial reduction in its interaction with nucleosomes compared to
naked DNA, also in a lesion orientation-dependent manner, reinforcing the concept
that reduction in APE1 activity on nucleosomes is due to occlusion from its
abasic DNA substrate by the histones. These results suggest that APE1 activity in
nucleosomes, like BER glycosylases, is primarily regulated by its chance
interactions with transiently exposed lesions.
PMID- 25847268
TI - Acute and chronic administration of gold nanoparticles cause DNA damage in the
cerebral cortex of adult rats.
AB - The use of gold nanoparticles is increasing in medicine; however, their toxic
effects remain to be elucidated. Studies show that gold nanoparticles can cross
the blood-brain barrier, as well as accumulate in the brain. Therefore, this
study was undertaken to better understand the effects of gold nanoparticles on
rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult
rats submitted to acute and chronic administration of gold nanoparticles of two
different diameters: 10 and 30nm. During acute administration, adult rats
received a single intraperitoneal injection of either gold nanoparticles or
saline solution. During chronic administration, adult rats received a daily
single injection for 28 days of the same gold nanoparticles or saline solution.
Twenty-four hours after either single (acute) or last injection (chronic), the
rats were euthanized by decapitation, their brains removed, and the cerebral
cortices isolated for evaluation of DNA damage parameters. Our study showed that
acute administration of gold nanoparticles in adult rats presented higher levels
of damage frequency and damage index in their DNA compared to the control group.
It was also observed that gold nanoparticles of 30nm presented higher levels of
damage frequency and damage index in the DNA compared to the 10nm ones. When
comparing the effects of chronic administration of gold nanoparticles of 10 and
30nm, we observed that occurred significant different index and frequency damage,
comparing with control group. However, there is no difference between the 10 and
30nm groups in the levels of DNA damage for both parameters of the Comet assay.
Results suggest that gold nanoparticles for both sizes cause DNA damage for
chronic as well as acute treatments, although a higher damage was observed for
the chronic one.
PMID- 25847269
TI - Expression and methylation of DNA repair genes in lens epithelium cells of age
related cataract.
AB - The development of age-related cataract (ARC) is associated with DNA damage of
the lens epithelial cells (LECs). This study aimed to investigate the expression
level of DNA repair genes in LECs of ARC and examine whether any altered
expression observed could result from DNA methylation of the promoter region of
the genes. The expression levels of DNA repair genes were evaluated by microarray
analysis. The results were further confirmed by qRT-PCR. DNA methylation of genes
with altered expression was determined by bisulfite-specific (BSP) PCR. The mRNA
levels of 10 DNA repair genes were decreased and the level of 1 DNA repair gene
was increased in LECs of ARC patients compared with controls. The promoter region
of the MGMT gene was hypermethylated in ARC tissue compared to controls. The data
provide evidence that altered expression of DNA repair genes is associated with
pathogenesis of ARC. DNA methylation of MGMT may regulate the expression of the
gene and be involved in the development of ARC.
PMID- 25847270
TI - Functional characterization of genetic polymorphisms in the H2AFX distal
promoter.
AB - Due to the critical role of the H2AX histone variant in double-strand break
repair, genetic variants in the H2AX gene, H2AFX, may influence cancer
susceptibility. Genetic association studies have correlated H2AFX upstream
variants with cancer risk; however it is unclear if any are causal. H2AFX has at
least two alternate transcripts that encode the same reading frame; a short 0.6kb
transcript that lacks an intron or poly-A tail and is predicted to be highly
expressed during the replication stage of the cell cycle, and a long 1.6kb poly-A
tailed transcript that is expressed in a replication-independent manner. To
examine the functional impact of the rs643788, rs8551, rs7759, and rs2509049
upstream variants, we characterized their influence on gene expression, cell
survival after DNA assault, and transcription factor binding. Analysis of allelic
imbalance using quantitative sequencing of cDNA from lymphoblast cell lines did
not reveal any difference in expression of the 1.6kb polyadenylated transcript
between the common H2AFX upstream haplotypes. We did, however, identify a
previously unreported 197 base pair intron in the H2AFX 3'untranslated region
that appears to be present regardless of haplotype. Assessment of cell survival
after irradiation treatment did not show any difference in survival between cell
lines of different haplotypes. Gel shift assays revealed that the rs643788 C
allele disrupts YY1 transcription factor binding and the rs2509049 C allele binds
more strongly to a protein complex than does the rs2509049 T allele. Though we
did not identify any differences in expression or survival between haplotypes,
differential protein binding at two of the polymorphisms suggests further
functional analyses may reveal a role for these variants in influencing gene
expression at specific points of the cell cycle or in specific tissues.
PMID- 25847271
TI - Ethyl methanesulfonate induces mutations in Caenorhabditis elegans embryos at a
high frequency.
AB - Mutagenesis protocols typically call for exposure of late-stage larvae or adults
to a mutagen with the intention of inducing mutations in a robust germ line.
Instead, ca. 16,000 CB665 [unc-58(e665)] one- to four-cell embryos of the
nematode Caenorhabditis elegans were hand selected and exposed to ethyl
methanesulfonate (EMS) for 50min. Twenty-one reversion mutants were recovered, of
which 17 were intragenic suppressors of the e665 mutation. The mutation frequency
was 6.5-fold higher than when CB665 adults were similarly mutagenized, which was
predicted given that cell-cycle checkpoints are muted in C. elegans embryos. The
mutation spectrum was similar to that obtained after standard EMS mutagenesis.
PMID- 25847272
TI - Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or
radiosensitizing effects as elucidated by the PCC and G2-assay.
AB - Curcumin and trans-resveratrol are well-known antioxidant polyphenols with
radiomodulatory properties, radioprotecting non-cancerous cells while
radiosensitizing tumor cells. This dual action may be the result of their radical
scavenging properties and their effects on cell-cycle checkpoints that are
activated in response to radiation-induced chromosomal damage. It could be also
caused by their effect on regulatory pathways with impact on detoxification
enzymes, the up-regulation of endogenous protective systems, and cell-cycle
dependent processes of DNA damage. This work aims to elucidate the mechanisms
underlying the dual action of these polyphenols and investigates under which
conditions they exhibit radioprotecting or radiosensitizing properties. The
peripheral blood lymphocyte test system was used, applying concentrations ranging
from 1.4 to 140MUM curcumin and 2.2 to 220MUM trans-resveratrol. The experimental
design focuses first on their radioprotective effects in non-cycling lymphocytes,
as uniquely visualized using cell fusion-mediated premature chromosome
condensation, excluding, thus, cell-cycle interference to repair processes and
activation of checkpoints. Second, the radiosensitizing potential of these
chemicals on the induction of chromatid breaks in cultured lymphocytes following
G2-phase irradiation was evaluated by a standardized G2-chromosomal
radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint
abrogation and it was applied to obtain an internal control for radiosensitivity
testing, which simulates conditions similar to those of the highly radiosensitive
lymphocytes of AT patients. The results demonstrate for the first time the cell
cycle-dependent action of these polyphenols. When non-cycling cells are
irradiated, the radioprotective properties of curcumin and trans-resveratrol are
more prominent. However, when cycling cells are irradiated during G2-phase, the
radiosensitizing features of these compounds are more pronounced. This
observation offers a new biological basis for the mechanisms underlying the
action of these polyphenols in cancer radiotherapy.
PMID- 25847273
TI - Direct observation of preferential processing of clustered abasic DNA damages
with APE1 in TATA box and CpG island by reaction kinetics and fluorescence
dynamics.
AB - Sequences like the core element of TATA box and CpG island are frequently
encountered in the genome and related to transcription. The fate of repair of
clustered abasic sites in such sequences of genomic importance is largely
unknown. This prompted us to investigate the sequence dependence of cleavage
efficiency of APE1 enzyme at abasic sites within the core sequences of TATA box
and CpG island using fluorescence dynamics and reaction kinetics. Simultaneous
molecular dynamics study through steady state and time resolved fluorescence
spectroscopy using unique ethidium bromide dye release assay confirmed an
elevated amount of abasic site cleavage of the TATA box sequence as compared to
the core CpG island. Reaction kinetics showed that catalytic efficiency of APE1
for abasic site cleavage of core CpG island sequence was ~4 times lower as
compared to that of the TATA box. Higher value of Km was obtained from the core
CpG island sequence than the TATA box sequence. This suggests a greater binding
effect of APE1 enzyme on TATA sequence that signifies a prominent role of the
sequence context of the DNA substrate. Evidently, a faster response from APE1 was
obtained for clustered abasic damage repair of TATA box core sequences than CpG
island consensus sequences. The neighboring bases of the abasic sites in the
complementary DNA strand were found to have significant contribution in addition
to the flanking bases in modulating APE1 activity. The repair refractivity of the
bistranded clustered abasic sites arise from the slow processing of the second
abasic site, consequently resulting in decreased overall production of
potentially lethal double strand breaks.
PMID- 25847275
TI - Peroxide promoted tunable decarboxylative alkylation of cinnamic acids to form
alkenes or ketones under metal-free conditions.
AB - A tunable decarboxylative alkylation of cinnamic acids with alkanes was developed
to form alkenes or ketones under transition metal-free conditions. In the
presence of DTBP or DTBP/TBHP, the reaction gave alkenes and ketones respectively
via a radical mechanism in moderate to good yields.
PMID- 25847274
TI - Deletion of BRCA2 exon 27 causes defects in response to both stalled and
collapsed replication forks.
AB - BRCA2 is a tumor suppressor that maintains genomic integrity through double
strand break (DSB) repair and replication fork protection. The BRC motifs and an
exon 27-encoded domain (Ex27) of BRCA2 interact with the recombinase RAD51 to,
respectively, facilitate the formation and stability of a RAD51 filament on
single strand DNA. The BRC-RAD51 associations enable DSB repair while the Ex27
RAD51 association protects the nascent replication strand from MRE11-mediated
degradation. MRE11 is a nuclease that facilitates the generation of 3' overhangs
needed for homologous recombination (HR)-mediated DSB repair. Here we report the
dynamics of replication fork maintenance in mouse embryonic stem (ES) cells
deleted for Ex27 (brca2(lex1/lex2)) after exposure to hydroxyurea (HU) that
depletes nucleotides. HU conditions were varied from mild to severe. Mild
conditions induce an ATR-response to replication fork stalling while severe
conditions induce a DNA-PKCS-response to replication fork collapse and a DSB.
These responses were differentiated by replication protein A (RPA)
phosphorylation. We found that Ex27 deletion reduced MRE11 localization to
stalled, but not collapsed, replication forks and that Ex27-deletion caused a
proportionately more severe phenotype with HU dose. Therefore, the BRCA2 exon 27
domain maintains chromosomal integrity at both stalled and collapsed replication
forks consistent with involvement in both replication fork maintenance and double
strand break repair.
PMID- 25847276
TI - Therapist competence in global mental health: Development of the ENhancing
Assessment of Common Therapeutic factors (ENACT) rating scale.
AB - Lack of reliable and valid measures of therapist competence is a barrier to
dissemination and implementation of psychological treatments in global mental
health. We developed the ENhancing Assessment of Common Therapeutic factors
(ENACT) rating scale for training and supervision across settings varied by
culture and access to mental health resources. We employed a four-step process in
Nepal: (1) Item generation: We extracted 1081 items (grouped into 104 domains)
from 56 existing tools; role-plays with Nepali therapists generated 11 additional
domains. (2) Item relevance: From the 115 domains, Nepali therapists selected 49
domains of therapeutic importance and high comprehensibility. (3) Item utility:
We piloted the ENACT scale through rating role-play videotapes, patient session
transcripts, and live observations of primary care workers in trainings for
psychological treatments and the Mental Health Gap Action Programme (mhGAP). (4)
Inter-rater reliability was acceptable for experts (intraclass correlation
coefficient, ICC(2,7) = 0.88 (95% confidence interval (CI) 0.81-0.93), N = 7) and
non-specialists (ICC(1,3) = 0.67 (95% CI 0.60-0.73), N = 34). In sum, the ENACT
scale is an 18-item assessment for common factors in psychological treatments,
including task-sharing initiatives with non-specialists across cultural settings.
Further research is needed to evaluate applications for therapy quality and
association with patient outcomes.
PMID- 25847277
TI - Enhancement of the photoluminescence and long afterglow properties of
Sr2MgSi2O7:Eu(2+) phosphor by Dy(3+) co-doping.
AB - Sr2MgSi2O7:Eu(2+) and Sr2MgSi2O7:Eu(2+),Dy(3+) long afterglow phosphors were
synthesized under a weak reducing atmosphere by the traditional high temperature
solid state reaction method. The synthesized phosphors were characterized by
powder X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and
photo-, thermo- and mechanoluminescence spectroscopic techniques. The phase
structure of the sintered phosphor was an akermanite type structure, which
belongs to tetragonal crystallography. The thermoluminescence properties of these
phosphors were investigated and compared. Under ultraviolet light excitation, the
emission spectra of both prepared phosphors were composed of a broad emission
band peaking at 470 nm. When the Sr2MgSi2O7:Eu(2+) phosphor was co-doped with
Dy(3+), the photoluminescence (PL), afterglow and mechanoluminescence (ML)
intensity were strongly enhanced. The decay graph indicated that both the
sintered phosphors contained fast decay and slow decay processes. The ML
intensities of Sr2MgSi2O7:Eu(2+) and Sr2MgSi2O7:Eu(2+),Dy(3+) phosphors were
increased proportionally with increasing impact velocity, a finding that suggests
that these phosphors could be used as sensors to detect the stress of an object.
PMID- 25847278
TI - Self-synthesized extracellular matrix contributes to mature adipose tissue
regeneration in a tissue engineering chamber.
AB - The development of an engineered adipose tissue substitute capable of supporting
reliable, predictable, and complete fat tissue regeneration would be of value in
plastic and reconstructive surgery. For adipogenesis, a tissue engineering
chamber provides an optimized microenvironment that is both efficacious and
reproducible; however, for reasons that remain unclear, tissues regenerated in a
tissue engineering chamber consist mostly of connective rather than adipose
tissue. Here, we describe a chamber-based system for improving the yield of
mature adipose tissue and discuss the potential mechanism of adipogenesis in
tissue-chamber models. Adipose tissue flaps with independent vascular pedicles
placed in chambers were implanted into rabbits. Adipose volume increased
significantly during the observation period (week 1, 2, 3, 4, 16).
Histomorphometry revealed mature adipose tissue with signs of adipose tissue
remolding. The induced engineered constructs showed high-level expression of
adipogenic (peroxisome proliferator-activated receptor gamma), chemotactic
(stromal cell-derived factor 1a), and inflammatory (interleukin 1 and 6) genes.
In our system, the extracellular matrix may have served as a scaffold for cell
migration and proliferation, allowing mature adipose tissue to be obtained in a
chamber microenvironment without the need for an exogenous scaffold. Our results
provide new insights into key elements involved in the early development of
adipose tissue regeneration.
PMID- 25847279
TI - Fractal and stochastic geometry inference for breast cancer: a case study with
random fractal models and Quermass-interaction process.
AB - Fractals are models of natural processes with many applications in medicine. The
recent studies in medicine show that fractals can be applied for cancer detection
and the description of pathological architecture of tumors. This fact is not
surprising, as due to the irregular structure, cancerous cells can be interpreted
as fractals. Inspired by Sierpinski carpet, we introduce a flexible parametric
model of random carpets. Randomization is introduced by usage of binomial random
variables. We provide an algorithm for estimation of parameters of the model and
illustrate theoretical and practical issues in generation of Sierpinski gaskets
and Hausdorff measure calculations. Stochastic geometry models can also serve as
models for binary cancer images. Recently, a Boolean model was applied on the 200
images of mammary cancer tissue and 200 images of mastopathic tissue. Here, we
describe the Quermass-interaction process, which can handle much more variations
in the cancer data, and we apply it to the images. It was found out that
mastopathic tissue deviates significantly stronger from Quermass-interaction
process, which describes interactions among particles, than mammary cancer tissue
does. The Quermass-interaction process serves as a model describing the tissue,
which structure is broken to a certain level. However, random fractal model fits
well for mastopathic tissue. We provide a novel discrimination method between
mastopathic and mammary cancer tissue on the basis of complex wavelet-based self
similarity measure with classification rates more than 80%. Such similarity
measure relates to Hurst exponent and fractional Brownian motions. The R package
FractalParameterEstimation is developed and introduced in the paper.
PMID- 25847280
TI - Mildronate (Meldonium) in professional sports - monitoring doping control urine
samples using hydrophilic interaction liquid chromatography - high
resolution/high accuracy mass spectrometry.
AB - To date, substances such as Mildronate (Meldonium) are not on the radar of anti
doping laboratories as the compound is not explicitly classified as prohibited.
However, the anti-ischemic drug Mildronate demonstrates an increase in endurance
performance of athletes, improved rehabilitation after exercise, protection
against stress, and enhanced activations of central nervous system (CNS)
functions. In the present study, the existing evidence of Mildronate's usage in
sport, which is arguably not (exclusively) based on medicinal reasons, is
corroborated by unequivocal analytical data allowing the estimation of the
prevalence and extent of misuse in professional sports. Such data are vital to
support decision-making processes, particularly regarding the ban on drugs in
sport. Due to the growing body of evidence (black market products and athlete
statements) concerning its misuse in sport, adequate test methods for the
reliable identification of Mildronate are required, especially since the
substance has been added to the 2015 World Anti-Doping Agency (WADA) monitoring
program. In the present study, two approaches were established using an in-house
synthesized labelled internal standard (Mildronate-D3 ). One aimed at the
implementation of the analyte into routine doping control screening methods to
enable its monitoring at the lowest possible additional workload for the
laboratory, and another that is appropriate for the peculiar specifics of the
analyte, allowing the unequivocal confirmation of findings using hydrophilic
interaction liquid chromatography-high resolution/high accuracy mass spectrometry
(HILIC-HRMS). Here, according to applicable regulations in sports drug testing, a
full qualitative validation was conducted. The assay demonstrated good
specificity, robustness (rRT=0.3%), precision (intra-day: 7.0-8.4%; inter-day:
9.9-12.9%), excellent linearity (R>0.99) and an adequate lower limit of detection
(<10 ng/mL).
PMID- 25847281
TI - Oxygen uptake kinetics and exercise capacity in children with cystic fibrosis.
AB - Exercise capacity, an objective measure of exercise intolerance, is known to
predict quality of life and mortality in cystic fibrosis (CF). The mechanisms for
exercise intolerance in patients with cystic fibrosis (CF), however, have yet to
be fully elucidated. Accordingly, this study sought to investigate oxygen uptake
kinetics and the impact of fat-free mass (FFM) on exercise capacity in young
patients with CF. 16 young patients with CF (age 13 +/- 4 years; 10 female) and
15 matched controls (age 14 +/- 3 years; nine female) participated. Pulmonary
function and a maximal exercise test on a cycle ergometer using the Godfrey
protocol were performed. Exercise capacity (VO2 peak), VO2 response time (VO2
RT), and functional VO2 gain (DeltaVO2 /DeltaWR) were all determined. Lung
function was the only demographic parameter significantly lower (P < 0.05) in CF
compared to controls. Exercise capacity was lower in CF (P < 0.014) only when VO2
peak was normalized for FFM (43.5 +/- 7.7 vs. 50.6 +/- 7.4 ml/kg-FFM/min) or
expressed as % predicted (70.1 +/- 14.3 vs. 85.4 +/- 16.0%). The VO2 RT was
slower (36.1 +/- 15.1 vs. 25.0 +/- 12.4 sec; P = 0.03) and the DeltaVO2 /DeltaWR
slope was lower (8.4 +/- 3 ml/min/watt vs. 10.1 +/- 1.4 ml/min/watt; P = 0.02) in
patients compared to controls, respectively. In conclusion, a delayed VO2
response time coupled with the lower functional VO2 gain (DeltaVO2 /DeltaWR)
suggest that young patients with CF have impairment in oxygen transport and
oxygen utilization by the muscles. These data in addition to differences in VO2
peak normalized for FFM provide some insight that muscle mass and muscle
metabolism contribute to exercise intolerance in CF.
PMID- 25847283
TI - Characterization of the effects of three Lactobacillus species on the function of
chicken macrophages.
AB - Lactobacillus acidophilus, Lactobacillus reuteri and Lactobacillus salivarius can
influence the adaptive immune responses in chickens but vary in their ability to
do so. The present study attempted to identify how these three bacteria alter the
innate immune system. A chicken macrophage cell line, MQ-NCSU, was co-cultured
with the three live Lactobacillus species, alone or in combination, grown at
different temperatures for various durations of time. Late exponential growth
phase bacteria were more immunostimulatory, while bacterial growth temperature
had little effect. L. acidophilus and L. salivarius significantly increased
nitric oxide (NO) production and phagocytosis, while L. reuteri did not. In fact,
L reuteri was shown to inhibit NO production of macrophages when co-cultured with
the other bacteria or when cells were pre-treated with LPS. The results
demonstrate a possible molecular mechanism for the immunomodulatory effects of L.
acidophilus and L. salivarius, and a unique immunomodulatory ability of L.
reuteri.
PMID- 25847284
TI - Papillary meningioma in the dog: A clinicopathological case series study.
AB - Papillary meningioma (PM) is one of the most aggressive variants of meningioma in
humans and classified as grade III by WHO system. To date, the biological
behavior of PM is still not clear in dogs. This study investigated the
correlation between histopathological findings of 16 canine PMs and follow up
data. Moreover, the expression of doublecortin, E-cadherin, and N-cadherin was
investigated by immunohistochemistry. The supratentorial compartment resulted the
most common involved. Despite the low grade of histological malignancy, 87.5% of
dogs that underwent surgery experienced tumor recurrence. Intratumoral necrosis
was observed in a strict correlation with malignancy histological parameter and
tumor recurrence. The post-surgery mean survival time was much lower than thus
observed in the most common histological subtypes. This data were also confirmed
in dogs that received a conservative treatment alone. Tumors with a severe
clinical behavior showed a high N-cadherin expression versus a low or absent E
cadherin expression.
PMID- 25847282
TI - Pig-to-baboon heterotopic heart transplantation--exploratory preliminary
experience with pigs transgenic for human thrombomodulin and comparison of three
costimulation blockade-based regimens.
AB - BACKGROUND: Three costimulation blockade-based regimens have been explored after
transplantation of hearts from pigs of varying genetic backgrounds to determine
whether CTLA4-Ig (abatacept) or anti-CD40mAb+CTLA4-Ig (belatacept) can
successfully replace anti-CD154mAb. METHODS: All pigs were on an alpha1,3
galactosyltransferase gene-knockout/CD46 transgenic (GTKO.CD46) background.
Hearts transplanted into Group A baboons (n=4) expressed additional CD55, and
those into Group B (n=3) expressed human thrombomodulin (TBM). Immunosuppression
included anti-thymocyte globulin with anti-CD154mAb (Regimen 1: n=2) or abatacept
(Regimen 2: n=2) or anti-CD40mAb+belatacept (Regimen 3: n=2). Regimens 1 and 2
included induction anti-CD20mAb and continuous heparin. One further baboon in
Group B (B16311) received a modified Regimen 1. Baboons were followed by
clinical/laboratory monitoring of immune/coagulation parameters. At biopsy, graft
failure, or euthanasia, the graft was examined by microscopy. RESULTS: Group A
baboons survived 15 to 33 days, whereas Group B survived 52, 99, and 130 days,
respectively. Thrombocytopenia and reduction in fibrinogen occurred within 21
days in Group A, suggesting thrombotic microangiopathy (TM), confirmed by
histopathology. In Group B, with follow-up for >4 m, areas of myofiber
degeneration and scarring were seen in two hearts at necropsy. A T-cell response
was documented only in baboons receiving Regimen 2. CONCLUSIONS: The combination
of anti-CD40mAb+belatacept proved effective in preventing a T-cell response. The
expression of TBM prevented thrombocytopenia and may possibly delay the
development of TM and/or consumptive coagulopathy.
PMID- 25847285
TI - The impact of vehicle motion during transport on animal welfare.
AB - Motion sickness is a common response in humans and some species of farm livestock
during transport, but research on the impact of motion has been primarily focused
on the use of animal models for humans. During livestock transportation, animals
seek to minimise uncontrolled movements to reduce energy consumption and maintain
posture. Road and sea transport of livestock can produce motion sickness and
stress responses. Clinical signs are the result of autonomous nervous system
activation. Studies conducted on road transportation effects in domestic animals
showed several motion sickness behaviours including vomiting and, in ruminants, a
reduction in rumination. However, there is a lack of knowledge on the impact of
sea transport motion. Despite the paucity of data on livestock, there is
sufficient evidence to believe that motion might affect animal welfare when
animals are transported by road or sea.
PMID- 25847286
TI - Trp(250) -hK2 is defective in intracellular trafficking and activates the
unfolded protein response.
AB - hK2, a member of the kallikrein protease family encoded by KLK2, is expressed
exclusively in prostate and is a putative adjunct tumor marker for prostate
cancer screening. The T allele of rs198977, a single nucleotide polymorphism in
exon 5 of KLK2, codes for W-hK2 and is associated with lower serum hK2 levels and
higher risk of prostate cancer than the C allele encoding R-hK2. To elucidate the
mechanism that underlies this SNP's function, we transfected plasmids expressing
R-hK2 or W-hK2 into PC3, HeLa and HEK293A cells and measured the hK2 level in
cell lysates and conditioned media. The level of W-hK2 was lower than R-hK2 in
conditioned media but was not different from R-hK2 in cell lysates. W-hK2 was
hardly colocalized with Golgi-targeted fluorescent protein whereas R-hK2
colocalized. Reporter assays related to the unfolded protein response (UPR) and
phospho-eIF2alpha immunoblot showed that W-hK2 increased UPR activity more than R
hK2. These results indicated that W-hK2 had a defect in cellular trafficking from
the ER to the Golgi complex due to its misfolding and that it activated the UPR,
suggesting a mechanism to explain the association of the T allele with higher
prostate cancer risk.
PMID- 25847287
TI - Dual Trajectories of Cigarette Smoking and Smokeless Tobacco Use From Adolescence
to Midlife Among Males in a Midwestern US Community Sample.
AB - INTRODUCTION: Identifying trajectories of tobacco use is critical for
understanding its natural history and targeting interventions, but research on
trajectories of smokeless tobacco and dual use of smokeless tobacco and
cigarettes is very limited. This study identified tobacco use trajectories from
adolescence to midlife and tested correlates of trajectory group membership.
METHODS: This study included all male participants in a longitudinal study who
reported cigarette smoking or smokeless tobacco use in 1987, 1993, 1999, 2005, or
2011 (N = 2230). Group-based trajectory analyses were conducted with zero
inflated Poisson models. Analysis of covariance was used to test adolescent
health beliefs associated with trajectory group membership. RESULTS: Five smoking
trajectory groups were identified: (1) consistent abstinence from cigarettes; (2)
late onset intermittent, then cessation; (3) early onset regular, then cessation;
(4) delayed onset regular, then cessation; and (5) consistent regular. Four
smokeless tobacco trajectory groups were identified: (1) early onset, then
cessation; (2) consistent abstinence from smokeless tobacco; (3) late onset,
escalating; and (4) consistent regular. The proportion of participants in
trajectory groups representing dual use was low. Adolescent beliefs favorable to
smoking and smokeless tobacco were associated with membership in consistent
regular use groups. CONCLUSIONS: The prevalence of dual use of cigarettes and
smokeless tobacco was low, and there was little evidence to suggest switching
between tobacco products. Participants who held more positive beliefs about
smoking and smokeless tobacco as adolescents were more likely to be consistent
regular users of cigarettes and smokeless tobacco into adulthood.
PMID- 25847288
TI - The Association of Panic Disorder, Posttraumatic Stress Disorder, and Major
Depression With Smoking in American Indians.
AB - INTRODUCTION: Rates of cigarette smoking are disproportionately high among
American Indian populations, although regional differences exist in smoking
prevalence. Previous research has noted that anxiety and depression are
associated with higher rates of cigarette use. We asked whether lifetime panic
disorder, posttraumatic stress disorder, and major depression were related to
lifetime cigarette smoking in two geographically distinct American Indian tribes.
METHODS: Data were collected in 1997-1999 from 1506 Northern Plains and 1268
Southwest tribal members; data were analyzed in 2009. Regression analyses
examined the association between lifetime anxiety and depressive disorders and
odds of lifetime smoking status after controlling for sociodemographic variables
and alcohol use disorders. Institutional and tribal approvals were obtained for
all study procedures, and all participants provided informed consent. RESULTS:
Odds of smoking were two times higher in Southwest participants with panic
disorder and major depression, and 1.7 times higher in those with posttraumatic
stress disorder, after controlling for sociodemographic variables. After
accounting for alcohol use disorders, only major depression remained
significantly associated with smoking. In the Northern Plains, psychiatric
disorders were not associated with smoking. Increasing psychiatric comorbidity
was significantly linked to increased smoking odds in both tribes, especially in
the Southwest. CONCLUSIONS: This study is the first to examine the association
between psychiatric conditions and lifetime smoking in two large, geographically
diverse community samples of American Indians. While the direction of the
relationship between nicotine use and psychiatric disorders cannot be determined,
understanding unique social, environmental, and cultural differences that
contribute to the tobacco-psychiatric disorder relationship may help guide tribe
specific commercial tobacco control strategies.
PMID- 25847289
TI - Combinations of CYP2A6*4 and Glutathione S-Transferases Gene Polymorphisms Modify
the Association Between Maternal Secondhand Smoke Exposure During Pregnancy and
Small-for-Gestational-Age.
AB - INTRODUCTION: Risk of small-for-gestational-age (SGA) birth varied considerably
in women exposed to secondhand smoke (SHS) during pregnancy. We examined whether
this variation was explained by mothers' one Phase I (CYP2A6*4, activation of
tobacco toxics) and two Phase II (GSTM1 and GSTT1, detoxification) metabolic
genotypes. METHODS: We enrolled 468 Chinese pregnant women (115 delivering SGA
and 353 delivering non-SGA newborns) shortly before delivery. SHS exposure during
pregnancy was defined as self-reported daily exposure time being more than 0
minute. We fitted multivariable logistic regression models to examine whether
CYP2A6*4, GSTM1, and GSTT1 gene polymorphsims and their combinations modified the
association between SHS exposure and SGA. RESULTS: In the total sample, more
mothers of SGA newborns were exposed to SHS during pregnancy than mothers of non
SGA newborns (38.3% vs. 31.4%). CYP2A6*4, GSTM1, and GSTT1 genes alone could not
modify the association between SHS exposure and SGA. The combination of CYP2A6*4
and GSTT1 high-risk genotypes (CYP2A6*1/*1 and GSTT1-absent [high-risk] vs. other
combinations as a whole [low-risk]) significantly (P value, .045) modified the
association between SHS exposure and SGA. Among mothers with high-risk genotypes,
SHS during pregnancy was significantly associated with SGA (confounder-adjusted
odds ratio, 2.31 [95% confidence interval, 1.20-4.42]). Among mothers with low
risk genotypes, however, SHS exposure during pregnancy was not associated with
SGA (1.14 [0.64-2.04]). CONCLUSIONS: Chinese pregnant women with the combination
of CYP2A6*1/*1 and GSTT1-absent genotypes are at particularly high-risk of SHS
related SGA.
PMID- 25847290
TI - Smoking Status Confirmation by Proxy: Validation in a Smoking Cessation Trial.
AB - INTRODUCTION: Biochemical confirmation (BC) of self-report is the gold standard
of evidence for abstinence in smoking cessation research, but difficulty in
obtaining samples may bias estimates of quit rates. Proxy confirmation (PC) has
not been validated in cessation trials. We assessed the feasibility and validity
of PC in a cessation trial for hospitalized smokers. METHODS: We enrolled 402
daily cigarette smokers during a hospital admission. At enrollment, participants
provided demographics, smoking history, and named proxies to confirm their
smoking status at follow-up. Participants provided self-reported (SR) 7-day
tobacco abstinence by telephone at 6 months post-discharge. SR quitters were
asked to mail a saliva sample for BC. Incentives were offered for survey
completion ($20) and returned samples ($50). We called proxies for all those with
SR to obtain PC. Quit rates were calculated with missing data indicating smoking.
We assessed associations of nonresponse with baseline characteristics using chi
squared tests and logistic regression. We calculated the sensitivity and
specificity of PC in detecting smokers as determined by BC. RESULTS: All patients
named at least one proxy. Response rates were 82% for SR, 84% for PC, and 69% for
BC. Observed participant characteristics were unrelated to provision of sample
for BC. Estimated quit rates were 35% for SR, 27% for SR + PC, 21% for SR + BC
and 27% for SR + BC or PC. Sensitivity of PC was not higher than SR (73% vs.
77%); specificity was lower (84% vs. 100%). CONCLUSION: PC was feasible but not
superior to self-report in a cessation trial.
PMID- 25847291
TI - Smoke-Free School Policy and Exposure to Secondhand Smoke: A Quasi-Experimental
Analysis.
AB - INTRODUCTION: Tobacco control prevention efforts are important to protect people
from exposure to dangerous tobacco smoke, support cessation, and reduce tobacco
use initiation. While smoke-free laws have been a widespread tobacco control
strategy, little work has been done to examine the impact of smoke-free school
policies. The objective of this study is to evaluate the impact of provincial
smoke-free school ground policies on youth-reported exposure to secondhand smoke
(SHS) on school property. METHODS: This study used a nationally representative
sample of 20 388 youth aged 15-18 from the 2005-2012 Canadian Tobacco Use
Monitoring Survey. A quasi-experimental design was used to evaluate the impact of
smoke-free school policies on SHS exposure. RESULTS: Approximately over half
(52%) of respondents reported SHS exposure on a school property in the past
month. Smoke-free school policy had a statistically significant effect on SHS
exposure. Specifically, the adoption of smoke-free school reduced the probability
of SHS exposure by about 8 percentage points. Respondents who were smokers were
more likely to report being exposed to SHS than nonsmokers. Likewise, those
living in urban areas had higher probability of being exposed to SHS than those
living in rural parts of Canada. CONCLUSIONS: Reported exposure to tobacco smoke
did decrease after the introduction of smoke-free ground policies; however,
almost half of high-school aged youth report exposure in the last month. Across
Canada, provincial health authorities as well as school administers may need to
assess the implementation of these smoke-free policies and improve enforcement
strategies to further reduce exposure to dangerous SHS.
PMID- 25847293
TI - Relapse-Prevention Booklets as an Adjunct to a Tobacco Quitline: A Randomized
Controlled Effectiveness Trial.
AB - INTRODUCTION: Relapse prevention (RP) remains a major challenge to smoking
cessation. Previous research found that a set of self-help RP booklets
significantly reduced smoking relapse. This study tested the effectiveness of RP
booklets when added to the existing services of a telephone quitline. METHODS:
Quitline callers (N = 3458) were enrolled after their 2-week quitline follow-up
call and randomized to one of three interventions: (1) Usual Care: standard
intervention provided by the quitline, including brief counseling and nicotine
replacement therapy; (2) Repeated Mailings (RM): eight Forever Free RP booklets
sent to participants over 12 months; and (3) Massed Mailings: all eight Forever
Free RP booklets sent upon enrollment. Follow-ups were conducted at 6-month
intervals, through 24 months. The primary outcome measure was 7-day-point
prevalence-abstinence. RESULTS: Overall abstinence rates were 61.0% at baseline,
and 41.9%, 42.7%, 44.0%, and 45.9% at the 6-, 12-, 18- and 24-month follow-ups,
respectively. Although RM produced higher abstinence rates, the differences did
not reach significance for the full sample. Post-hoc analyses of at-risk
subgroups revealed that among participants with high nicotine dependence (n =
1593), the addition of RM materials increased the abstinence rate at 12 months
(42.2% vs. 35.2%; OR = 1.38; 95% CI = 1.03% to 1.85%; P = .031) and 24 months
(45% vs. 38.8%; OR = 1.31; 95% CI = 1.01% to 1.73%; P = .046). CONCLUSIONS:
Sending self-help RP materials to all quitline callers appears to provide little
benefit to deterring relapse. However, selectively sending RP booklets to callers
explicitly seeking assistance for RP and those identified as highly dependent on
nicotine might still prove to be worthwhile.
PMID- 25847294
TI - Corneal hypoesthesia with normal sub-basal nerve density following surgery for
trigeminal neuralgia.
AB - PURPOSE: To evaluate the corneal sub-basal nerve plexus in patients presenting
with hypoesthesia following surgery for trigeminal neuralgia. METHODS: Twenty-one
patients who had unilateral medically uncontrolled trigeminal neuralgia and
underwent ipsilateral surgery from 2006 to 2012 were included. Of these, 10 had
microvascular decompression (MVD group) and 11 had balloon compression of the
trigeminal ganglion (BC group). Slit lamp examination, Cochet-Bonnet
aesthesiometery and in vivo confocal microscopy were carried out on both eyes of
each patient. Nerve density data were statistically analysed. RESULTS: Corneal
sensations and sub-basal nerve densities in MVD group were normal and equal in
both the operated and unoperated sides, indicating that there was no intra
operative damage of the ophthalmic division of the trigeminal nerve (V1).
However, those in BC group, despite having significantly reduced corneal
sensations on the operated side (p = 0.007), did not demonstrate any significant
difference in their sub-basal nerve densities (p = 0.477). No patient had any
ocular symptoms. CONCLUSIONS: This study supports the hypothesis that complete
ganglionic damage and/or postganglionic damage of V1 results in corneal
hypoesthesia and neurotrophic keratitis, but partial ganglionic or preganglionic
damage would preserve trophic function despite hypoesthesia and not result in
clinically significant symptoms or signs of neurotrophic keratitis. The trophic
and sensory functions of V1 are therefore independent and can be dissociated by
disease or injury.
PMID- 25847295
TI - Nonylphenol diethoxylate inhibits apoptosis induced in PC12 cells.
AB - Nonylphenol and short-chain nonylphenol ethoxylates such as NP2 EO are present in
aquatic environment as wastewater contaminants, and their toxic effects on
aquatic species have been reported. Apoptosis has been shown to be induced by
serum deprivation or copper treatment. To understand the toxicity of nonylphenol
diethoxylate, we investigated the effects of NP2 EO on apoptosis induced by serum
deprivation and copper by using PC12 cell system. Nonylphenol diethoxylate itself
showed no toxicity and recovered cell viability from apoptosis. In addition,
nonylphenol diethoxylate decreased DNA fragmentation caused by apoptosis in PC12
cells. This phenomenon was confirmed after treating apoptotic PC12 cells with
nonylphenol diethoxylate, whereas the cytochrome c release into the cytosol
decreased as compared to that in apoptotic cells not treated with nonylphenol
diethoxylates. Furthermore, Bax contents in apoptotic cells were reduced after
exposure to nonylphenol diethoxylate. Thus, nonylphenol diethoxylate has the
opposite effect on apoptosis in PC12 cells compared to nonylphenol, which
enhances apoptosis induced by serum deprivation. The difference in structure of
the two compounds is hypothesized to be responsible for this phenomenon. These
results indicated that nonylphenol diethoxylate has capability to affect cell
differentiation and development and has potentially harmful effect on organisms
because of its unexpected impact on apoptosis. (c) 2015 Wiley Periodicals, Inc.
Environ Toxicol 31: 1389-1398, 2016.
PMID- 25847296
TI - Cancer-related fatigue: a survey of health practitioner knowledge and practice.
AB - PURPOSE: This study aims to identify the current practices of health
professionals in the assessment and treatment of cancer-related fatigue (CRF).
METHODS: Health professionals working with oncology clients participated in an
electronic survey distributed via professional associations and oncology
societies. RESULTS: One hundred twenty-nine professionals from nursing, medical,
and allied health disciplines participated in an electronic survey. Overall,
there was a perception that CRF was inadequately managed at some facilities.
Routine fatigue screening processes in the workplace were reported by more than
half of participants; however, less than one quarter used a clinical guideline or
conducted in-depth CRF assessments. Awareness of interventions for CRF varied
amongst participants with one quarter able to list five appropriate interventions
for cancer-related fatigue. Access to services for managing fatigue was
inconsistent across service types, with post-treatment triage a high priority for
CRF in some organisations yet not others. Participants identified a need for
improved guidelines, enhanced expertise and better access to services for people
with CRF. CONCLUSIONS: There is a need for further education in CRF management
for a range of health disciplines in oncology and additional resources to
facilitate translation of CRF guidelines into clinical practice.
PMID- 25847292
TI - Interaction of Cigarette Smoking History With APOE Genotype and Age on Amyloid
Level, Glucose Metabolism, and Neurocognition in Cognitively Normal Elders.
AB - INTRODUCTION: Chronic cigarette smoking is associated with increased risk for
Alzheimer's disease (AD). The goal of this study was to determine if smoking
history moderated the associations of age and APOE genotype (the most robust risk
factors for AD) on brain amyloid deposition, glucose metabolism, and
neurocognition in cognitively-normal elders. METHODS: Participants (n = 264) were
grouped according to their APOE epsilon4 carrier status (epsilon4 carrier:
APOE4+; non-epsilon4 carrier: APOE4-) and smoking status (smokers: at least 1
year of smoking during lifetime; never-smokers: no history of smoking).
Approximately 89% of the smoking sample was former-smokers. We specifically
tested for interactions of smoking status with APOE epsilon4 carrier status and
age on measures of cortical amyloid deposition, glucose metabolism, and
neurocognition. RESULTS: (1) smoking status interacted with APOE epsilon4 carrier
status, where smoker APOE4+ showed lower glucose metabolism and poorer auditory
verbal learning and memory than never-smoking APOE4-, never-smoking APOE4+, and
smoking APOE4-; (2) smoking status interacted with age on measures of semantic
fluency, processing speed/set-shifting and global neurocognition; smokers,
irrespective of APOE epsilon4 carrier status, demonstrated poorer performance
with increasing age than never-smokers; and (3) smoking APOE4+ and never-smoking
APOE4+ showed greater cortical amyloid deposition than never-smoking APOE4- and
smoking APOE4-. CONCLUSIONS: The findings indicate consideration of smoking
history is essential to both better understand the factors associated with
neurobiological and neurocognitive abnormalities in elders, and the risk for
development of AD-related neuropathology.
PMID- 25847298
TI - The combination of milatuzumab, a humanized anti-CD74 antibody, and veltuzumab, a
humanized anti-CD20 antibody, demonstrates activity in patients with relapsed and
refractory B-cell non-Hodgkin lymphoma.
AB - As a result of the anti-tumour activity observed in vitro and in vivo with
combined anti-CD20 and anti-CD74 antibodies, we initiated a phase I/II trial of
veltuzumab and milatuzumab in patients with relapsed or refractory B-cell non
Hodgkin lymphoma (NHL). Patients received an induction of veltuzumab 200 mg/m(2)
weekly combined with escalating doses of milatuzumab at 8, 16 and 20 mg/kg weekly
for 4 weeks. Patients without disease progression could receive an extended
induction with treatment on weeks 12, 20, 28 and 36. A total of 35 patients
enrolled on the study. Median age was 63 years, median number of prior therapies
was 3, and 63% of patients were rituximab refractory. No dose-limiting toxicities
were observed in the phase I study. Related grade 3-4 toxicities included
lymphopenia, leucopenia, neutropenia, anaemia, infusion reactions,
hyperglycaemia, fatigue and atrial tachycardia. Median weeks of therapy was 12
and 29% of patients completed all 36 weeks of therapy. The overall response rate
was 24%, median duration of response was 12 months, and responses were observed
at all dose levels and in 50% of patients refractory to rituximab. Combination
therapy with veltuzumab and milatuzumab demonstrated activity in a population of
heavily pre-treated patients with relapsed or refractory indolent NHL.
PMID- 25847297
TI - The HIV proteins Tat and Nef promote human bone marrow mesenchymal stem cell
senescence and alter osteoblastic differentiation.
AB - To maintain bone mass turnover and bone mineral density (BMD), bone marrow (BM)
mesenchymal stem cells (MSCs) are constantly recruited and subsequently
differentiated into osteoblasts. HIV-infected patients present lower BMD than non
HIV infected individuals and a higher prevalence of osteopenia/osteoporosis. In
antiretroviral treatment (ART)-naive patients, encoded HIV proteins represent
pathogenic candidates. They are released by infected cells within BM and can
impact on neighbouring cells. In this study, we tested whether HIV proteins Tat
and/or Nef could induce senescence of human BM-MSCs and reduce their capacity to
differentiate into osteoblasts. When compared to nontreated cells, MSCs
chronically treated with Tat and/or Nef up to 30 days reduced their proliferative
activity and underwent early senescence, associated with increased oxidative
stress and mitochondrial dysfunction. The antioxidant molecule N-acetyl- cysteine
had no or minimal effects on Tat- or Nef-induced senescence. Tat but not Nef
induced an early increase in NF-kappaB activity and cytokine/chemokine secretion.
Tat-induced effects were prevented by the NF-kappaB inhibitor parthenolide,
indicating that Tat triggered senescence via NF-kappaB activation leading to
oxidative stress. Otherwise, Nef- but not Tat-treated cells displayed early
inhibition of autophagy. Rapamycin, an autophagy inducer, reversed Nef-induced
senescence and oxidative stress. Moreover, Tat+Nef had cumulative effects.
Finally, Tat and/or Nef decreased the MSC potential of osteoblastic
differentiation. In conclusion, our in vitro data show that Tat and Nef could
reduce the number of available precursors by inducing MSC senescence, through
either enhanced inflammation or reduced autophagy. These results offer new
insights into the pathophysiological mechanisms of decreased BMD in HIV-infected
patients.
PMID- 25847299
TI - Retargeting of bile salt export pump and favorable outcome in children with
progressive familial intrahepatic cholestasis type 2.
AB - We investigated predictors of clinical evolution in progressive familial
intrahepatic cholestasis type 2 patients and how they relate to bile salt export
pump (BSEP) expression and its (re)targeting. Our retrospective study included 22
children with progressive familial intrahepatic cholestasis type 2. Clinical,
biochemical, and histological characteristics were reviewed on admittance and
following treatment with either ursodeoxycholic acid alone (10 mg/kg thrice
daily, n = 19) or partial biliary diversion (n = 3). Immunostaining of BSEP was
performed in 20 patients. Response to treatment was defined as normalization of
pruritus, disappearance of jaundice, and alanine aminotransferase (ALT) levels
<1.5 times the upper limit of normal. Ten of 22 patients were responders, and
paired biopsies were available in six. De novo or retargeted canalicular
expression of BSEP occurred in four of these six, two of whom exhibited baseline
intracellular expression. Twelve of 22 were nonresponders and exhibited earlier
onset of jaundice (<9 months), neonatal cholestasis, and higher ALT levels. An
ALT >165 IU/L produced 72% sensitivity and 55% specificity in predicting
nonresponse. Seven patients were still responding at last follow-up (median = 20
months, range 5-67 months). Three responders relapsed after 56, 72, and 82
months, respectively. Of nine surviving responders, median relapse-free survival
time was 72 months (95% confidence interval 48-96 months) and 5-year relapse-free
survival was 75% (95% confidence interval 33-100%). Intracellular BSEP at
baseline was seen in six, of whom five were responders. Genetic analysis was
performed in 17 of 22, confirming diagnosis in 13 (76%) and in four (24%) in whom
only heterozygous mutation was identified. CONCLUSION: De novo or retargeted
canalicular expression of BSEP occurs in treatment responders; children with late
onset presentation, lower ALT, and intracellular BSEP expression are likely to
respond, at least transiently, to nontransplant treatment.
PMID- 25847300
TI - A tale of two macrophages: to Shb or not to Shb.
PMID- 25847301
TI - Modulation of pre-attentive spectro-temporal feature processing in the human
auditory system by HD-tDCS.
AB - The present study examined the functional lateralization of the human auditory
cortex (AC) for pre-attentive spectro-temporal feature processing. By using high
definition transcranial direct current stimulation (HD-tDCS), we systematically
modulated neuronal activity of the bilateral AC. We assessed the influence of
anodal and cathodal HD-tDCS delivered over the left or right AC on auditory
mismatch negativity (MMN) in response to temporal as well as spectral deviants in
12 healthy subjects. The results showed that MMN to temporal deviants was
significantly enhanced by anodal HD-tDCS applied over the left AC only. Our data
indicate a left hemispheric dominance for the pre-attentive processing of low
level temporal information.
PMID- 25847302
TI - A forward to optimization of antivenom therapy: An in vivo study upon the
effectiveness of the antivenom against early and delayed nephrotoxicity induced
by the venom of the Iranian scorpion Hemiscorpius lepturus in rat.
AB - The aim of the present in vivo study was to identify the optimal effective dose,
the most favorable time and the route of administration of the available
polyvalent scorpion antivenom against the toxic effects induced by Hemiscorpius
lepturus (H. lepturus) venom in rat. The end point for assessment included
measurement of alanin-amino-peptidase (AAP) and N-acetyl-b-d-glucosaminidase
(NAG), biochemical urine analysis and histopathological assessment. The results
showed that a single subcutaneous 50 MUg of the venom produced significant
increase in the AAP and NAG enzyme activity, urinary biochemical parameters and
induced histopathological structural abnormalities in the renal system. The
optimal effective co-administered dose of the antivenom was 0.5 ml, which when
administered 1 and 2 h of envenomation by intravenous (IV) and subcutaneous (SC)
routes respectively produced significant protection against these toxic effects.
Prudently, the significance of these findings need to be assessed in further
clinical studies.
PMID- 25847304
TI - Stroke awareness and knowledge in an urban New Zealand population.
AB - BACKGROUND: Stroke is the third most common cause of death and a major cause of
chronic disability in New Zealand. Linked to risk factors that develop across the
life-course, stroke is considered to be largely preventable. This study assessed
the awareness of stroke risk, symptoms, detection, and prevention behaviors in an
urban New Zealand population. METHODS: Demographics, stroke risk factors
awareness, symptoms, responsiveness, and prevention behaviors were evaluated
using a structured oral questionnaire. Binomial logistic regression analyses were
used to identify predictors of stroke literacy. RESULTS: Although personal
experience of stroke increased awareness of symptoms and their likeliness to
indicate the need for urgent medical attention, only 42.7% of the respondents (n
= 850) identified stroke as involving both blood and the brain. Educational
attainment at or above a trade certificate, apprenticeship, or diploma increased
the awareness of stroke symptoms compared with those with no formal educational
attainment. Pacific Island respondents were less likely than New Zealand
Europeans to identify a number of stroke risk factors. Maori, Pacific Island, and
Asian respondents were less likely to identify symptoms of stroke and indicate
the need for urgent medical attention. CONCLUSIONS: The variability in stroke
awareness and knowledge may suggest the need to enhance stroke-related health
literacy that facilitates understanding of risk and of factors that reduce
morbidity and mortality after stroke in people of Maori and Pacific Island
descent and in those with lower educational attainment or socioeconomic status.
It is therefore important that stroke awareness campaigns include tailored
components for target audiences.
PMID- 25847303
TI - Upregulation of neuroglobin expression and changes in serum redox indices in a
rat model of middle cerebral artery occlusion.
AB - Neuroglobin (NGB) is a recently identified protein, which is localized in the
neurons and retinal cells of the central and peripheral nervous systems in
vertebrates. It is hypothesized to function as a scavenger for reactive oxygen
species, or as a stress-responsive sensor for signal transduction in hypoxic
ischemic brain insults. However, the mechanism underlying the physiological
function of this protein remains to be elucidated. In the present study, the
profiling of changes in the serum redox index of morphological features of the
hippocampus and cortex, and of the expression of NGB and hypoxia-inducible factor
1alpha (HIF-1alpha), are described in a rat middle cerebral artery occlusion
(MCAO) model. The necrotic zone of the rat neural tissues increased in size with
increasing reperfusion time, and different brain slices exhibited necrosis in
different regions. The number of NGB-positive hippocampal and cortical cells, as
well as NGB and HIF-1alpha transcript and protein levels in the ischemic cortex,
increased with increasing reperfusion time. NGB and HIF-1alpha mRNA and protein
levels peaked in the group that received reperfusion at 32 h after MCAO. These
findings indicated that HIF-1alpha may be involved in ischemic pathology in an
MCAO model and that NGB expression may be upregulated. Serum superoxide dismutase
(SOD) activity decreased and serum malondialdehyde (MDA) levels increased with
increasing reperfusion time, indicating that the redox potential increased
following MCAO. Serum SOD and MDA measurements may, therefore, be useful as
biomarkers for the early detection of ischemic injury in a clinical setting.
PMID- 25847305
TI - Non-vitamin k antagonist oral anticoagulants do not increase cerebral
microbleeds.
AB - BACKGROUND: Atrial fibrillation (AF) is a cardiac arrhythmia that frequently
induces ischemic strokes. Nowadays, non-vitamin K antagonist oral anticoagulants
(NOACs) have come into widespread use for cardiogenic embolism prevention in
place of warfarin. Recently, cerebral microbleeds (CMBs) have been noticed for
their potential implication in cerebral small vessel disease. We hypothesized
that NOACs do not have an unfavorable influence over cerebral small vessels and
investigated whether NOACs increase CMBs in AF patients in a prospective manner.
METHODS: We performed baseline magnetic resonance imaging (MRI) examinations on
the 69 enrolled AF patients and re-examined second round of MRI 1 year later. The
enrolled patients continued the same anticoagulation therapy during the meantime.
RESULTS: CMBs did not develop in the 23 patients with NOACs for 1 year. Nine
patients with antiplatelets also did not develop CMBs. On the other hand, 3 of 21
patients continued on warfarin and 3 of 9 with warfarin and antiplatelets had
CMBs. When divided into 2 groups according to whether the CMBs developed,
significant differences in the incidence of using NOACs were observed between the
2 groups (P = .02). A multivariate regression analysis showed that warfarin was
independently related to the new development of CMBs (hazard ratio, 10.75; 95%
confidence interval, 1.22-94.99; P = .03). CONCLUSIONS: This is the first report
to clarify that NOACs do not increase CMBs in AF patients longitudinally in 1
year. Further consideration will be continued with a much longer follow-up in
large samples.
PMID- 25847307
TI - Astrocytic mGluR5 and the tripartite synapse.
AB - In the brain, astrocytes occupy a key position between vessels and synapses.
Among their numerous functions, these glial cells are key partners of neurons
during synaptic transmission. Astrocytes detect transmitter release through
receptors and transporters at the level of their processes, which are in close
proximity to the tow neuronal elements of synapses. In response to transmitter
mediated activation, glial cells in turn regulate synaptic transmission and
neuronal excitability. This process has been reported to involve several glial
receptors. One of the best known of such receptors is the metabotropic
glutamatergic receptor subtype 5 (mGluR5). In the present review we will discuss
the implication of mGluR5s as detectors of synaptic transmission. In particular,
we will discuss how the functional properties and localization of these receptors
permit the detection of the synaptic signal in a defined temporal window and a
given spatial area around the synapse. Furthermore, we will review the impact of
their activation on synaptic transmission.
PMID- 25847309
TI - Welcome.
PMID- 25847308
TI - Different danger signals differently impact on microglial proliferation through
alterations of ATP release and extracellular metabolism.
AB - Microglia rely on their ability to proliferate in the brain parenchyma to sustain
brain innate immunity and participate in the reaction to brain damage. We now
studied the influence of different danger signals activating microglia, both
internal (typified by glutamate, associated with brain damage) and external
(using a bacterial lipopolysaccharide, LPS), on the proliferation of microglia
cells. We found that LPS (100 ng/mL) increased, whereas glutamate (0.5 mM)
decreased proliferation. Notably, LPS decreased whereas glutamate increased the
extracellular levels of ATP. In contrast, LPS increased whereas glutamate
decreased the extracellular catabolism of ATP into adenosine through ecto
nucleotidases and ecto-5'-nucleotidase. Finally, apyrase (degrades extracellular
ATP) abrogated glutamate-induced inhibition of microglia proliferation;
conversely, inhibitors of ecto-nucleotidases (ARL67156 or alpha,beta-methylene
ADP) and adenosine deaminase (degrades extracellular adenosine) abrogated the LPS
induced increase of microglia proliferation, which was blocked by a selective A2A
receptor antagonist, SCH58261 (50 nM). Overall, these results highlight the
importance of the extracellular purinergic metabolism to format microglia
proliferation and influence the spatio-temporal profile of neuroinflammation in
different conditions of brain damage.
PMID- 25847310
TI - Developmental status of 22 children with trisomy 18 and eight children with
trisomy 13: implications and recommendations.
AB - Trisomy 18 and trisomy 13 are conditions often referred to as "incompatible with
life" or "lethal anomalies." If there is long-term survival, the outlook is
considered "grim." Developmental status is presumed to be minimal. Yet, Baty et
al. [1994; 49:189-194] described a variety of developmental skills in their
sample. An additional 22 children with trisomy 18 and eight with trisomy 13 are
described here. A range of developmental skills is noted with strengths in the
language and communication, gross and fine motor and social-emotional domains
including indicating preferences, exploration of objects and a range of voluntary
mobility. These results serve to expand the knowledge base on developmental
status for these groups and advance the need to further explore developmental
abilities rather than focus on deficits. Avenues for future research,
implications, and recommendations are provided.
PMID- 25847311
TI - Linking environmental heavy metal concentrations and salinity gradients with
metal accumulation and their effects: A case study in 3 mussel species of Vitoria
estuary and Espirito Santo bay, Southeast Brazil.
AB - The present study was conducted to link the heavy metal load in three species of
mussels (Perna perna, Mytella falcata and Mytella guyanensis) from the estuaries
and bays around Vitoria island, south-east of Brazil, with the salinity gradient
and the heavy metal levels in the abiotic environment (including water, suspended
particulate matter (SPM) and sediment). Primarily based on the salinity gradient,
a total of 26 sites around Vitoria Island were selected for sampling of water,
SPM, sediments and organisms. Besides tissue metal levels, the condition index
and energy stores (glycogen, lipid and protein) were quantified as an indicator
of fitness in response to metal pollution. Dissolved metals in water indicate
that Cd and Mn content was higher along Espirito Santo Bay, while Al, Co, Cu, Cr
and Fe were elevated in the sites with low salinity such as river mouths,
estuarine and sewage canals. Likewise, suspended matter sampled from low salinity
sites showed a higher heavy metal load compared to moderate and high salinity
sites. Though mussels were sampled from different sites, the contamination for
Cd, Cu, Fe and Mn was higher in mussels inhabiting low salinity sites (M.
guyanensis and M. falcata) compared to P. perna, a high saline water inhabitant.
However, a higher Zn body burden was observed for P. perna compared to Mytella
species. Tissue Fe accumulation (but not Mn and Zn) correlated with heavy metal
levels in suspended material for all three species, and for M. falcata this
correlation also existed for Cd and Cu. Energy store and condition index in all
mussels varied depending on the sampling sites and correlated with salinity
gradient rather than tissue metal concentration. Overall, metal concentration in
mussels did not exceed the safe levels as per the international standards for
metals, and would be of no risk for human consumption.
PMID- 25847306
TI - Derivation and validation of a discharge disposition predicting model after acute
stroke.
AB - BACKGROUND: Discharge disposition planning is vital for poststroke patients. We
investigated clinical factors associated with discharging patients to nursing
homes, using the Taiwan Stroke Registry data collected from 39 major hospitals.
METHODS: We randomly assigned 21,575 stroke inpatients registered from 2006 to
2008 into derivation and validation groups at a 3-to-1 ratio. We used the
derivation group to develop a prediction model by measuring cumulative risk
scores associated with potential predictors: age, sex, hypertension, diabetes
mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types,
and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing
home care and odds ratio (OR) of nursing home care relative to home care by
cumulative risk scores were measured for the prediction. The area under the
receiver operating characteristic curve (AUROC) was used to assess the model
discrimination against the validation group. RESULTS: Except for hypertension,
all remaining potential predictors were significant independent predictors
associated with stroke patient disposition to nursing home care after discharge
from hospitals. The risk sharply increased with age and NIHSS. Patients with a
cumulative risk score of 15 or more had an OR of 86.4 for the nursing home
disposition. The AUROC plots showed similar areas under curves for the derivation
group (.86, 95% confidence interval [CI], .85-.87) and for the validation group
(.84, 95% CI, .83-.86). CONCLUSIONS: The cumulative risk score is an easy-to
estimate tool for preparing stroke patients and their family for disposition on
discharge.
PMID- 25847312
TI - iTRAQ analysis of hepatic proteins in free-living Mus spretus mice to assess the
contamination status of areas surrounding Donana National Park (SW Spain).
AB - This work aims to develop and integrate new -omics tools that would be applicable
to different ecosystem types for a technological updating of environmental
evaluations. We used a 2nd-generation (iTRAQ-8plex) proteomic approach to
identify/quantify proteins differentially expressed in the liver of free-living
Mus spretus mice from Donana National Park or its proximities. Mass spectrometry
was performed in an LTQ Orbitrap system for iTRAQ reporter ion quantitation and
protein identification using a Mus musculus database as reference. A prior IEF
step improved the separation of the complex peptide mixture. Over 2000 identified
proteins were altered, of which 118 changed by >=2.5-fold in mice from at least
two problem sites. Part of the results obtained with the iTRAQ analysis was
confirmed by Western blot. Over 75% of the 118 proteins were upregulated in
animals captured at polluted sites and only 16 proteins were downregulated.
Upregulated proteins were involved in stress response; cell proliferation and
apoptosis; signal transduction; metastasis or tumour suppression; xenobiotic
export or vesicular trafficking; and metabolism. The downregulated proteins, all
potentially harmful, were classified as oncoproteins and proteins favouring
genome instability. The iTRAQ results presented here demonstrated that the
survival of hepatic cells is compromised in animals living at polluted sites,
which showed deep alterations in metabolism and the signalling pathways. The
identified proteins may be useful as biomarkers of environmental pollution and
provide insight about the metabolic pathways and/or physiological processes
affected by pollutants in DNP and its surrounding areas.
PMID- 25847313
TI - Atmospheric transport of ozone between Southern and Eastern Asia.
AB - This study describes the effect of pollution transport between East Asia and
South Asia on tropospheric ozone (O3) using model results from the Task Force on
Hemispheric Transport of Air Pollution (TF HTAP). Ensemble mean O3 concentrations
are evaluated against satellite-data and ground observations of surface O3 at
four stations in India. Although modeled surface O3 concentrations are 1020ppb
higher than those observed, the relative magnitude of the seasonal cycle of O3 is
reproduced well. Using 20% reductions in regional anthropogenic emissions, we
quantify the seasonal variations in pollution transport between East Asia and
South Asia. While there is only a difference of 0.05 to 0.1ppb in the magnitudes
of the regional contributions from one region to the other, O3 from East Asian
sources affects the most densely populated parts of South Asia while Southern
Asian sources only partly affect the populated parts of East Asia. We show that
emission changes over East Asia between 2000 and 2010 had a larger impact on
populated parts of South Asia than vice versa. This study will help inform future
decisions on emission control policy over these regions.
PMID- 25847314
TI - Adsorption of phosphate from aqueous solutions and sewage using zirconium loaded
okara (ZLO): Fixed-bed column study.
AB - This study explores the potential of removing phosphorus from aqueous solutions
and sewage by Zr(IV)-loaded okara (ZLO) in the fixed-bed column. Soybean residue
(okara) was impregnated with 0.25M Zr(IV) solution to prepare active binding
sites for phosphate. The effect of several factors, including flow rate, bed
height, initial phosphorus concentration, pH and adsorbent particle size on the
performance of ZLO was examined. The maximum dynamic adsorption capacity of ZLO
for phosphorus was estimated to be 16.43mg/g. Breakthrough curve modeling
indicated that Adams-Bohart model and Thomas model fitted the experimental data
better than Yoon-Nelson model. After treatment with ZLO packed bed column, the
effluent could meet the discharge standard for phosphorus in Australia.
Successful desorption and regeneration were achieved with 0.2 NaOH and 0.1 HCl,
respectively. The results prove that ZLO can be used as a promising phosphorus
adsorbent in the dynamic adsorption system.
PMID- 25847315
TI - Seven-Point Subjective Global Assessment Is More Time Sensitive Than Conventional
Subjective Global Assessment in Detecting Nutrition Changes.
AB - BACKGROUND: It is important for nutrition intervention in malnourished patients
to be guided by accurate evaluation and detection of small changes in the
patient's nutrition status over time. However, the current Subjective Global
Assessment (SGA) is not able to detect changes in a short period. The aim of the
study was to determine whether the 7-point SGA is more time sensitive to
nutrition changes than the conventional SGA. METHODS: In this prospective study,
67 adult inpatients assessed as malnourished using both the 7-point SGA and
conventional SGA were recruited. Each patient received nutrition intervention and
was followed up after discharge. Patients were reassessed using both tools at 1,
3, and 5 months from baseline assessment. RESULTS: It took significantly shorter
time to see a 1-point change using the 7-point SGA compared with the conventional
SGA (median: 1 month vs 3 months, P = .002). The likelihood of at least a 1-point
change is 6.74 times greater in the 7-point SGA compared with the conventional
SGA after controlling for age, sex, and medical specialties (odds ratio, 6.74;
95% confidence interval, 2.88-15.80; P < .001). Fifty-six percent of patients who
had no change in SGA score had changes detected using the 7-point SGA. The level
of agreement was 100% (kappa = 1, P < .001) between the 7-point SGA and 3-point
SGA and 83% (kappa = 0.726, P < .001) between 2 blinded assessors for the 7-point
SGA. CONCLUSION: The 7-point SGA is more time sensitive in its response to
nutrition changes than the conventional SGA. It can be used to guide nutrition
intervention for patients.
PMID- 25847317
TI - Novel Antifungal Peptides Produced by Leuconostoc mesenteroides DU15 Effectively
Inhibit Growth of Aspergillus niger.
AB - The ability of Leuconostoc mesenteroides DU15 to produce antifungal peptides that
inhibit growth of Aspergillus niger was evaluated under optimum growth conditions
of 30 degrees C for 48 h. The cell-free supernatant showed inhibitory activity
against A. niger. Five novel peptides were isolated with the sequences GPFPL,
YVPLF, LLHGVPLP, GPFPLEMTLGPT, and TVYPFPGPL as identified by de novo sequencing
using PEAKS 6 software. Peptide LLHGVPLP was the only positively charged
(cationic peptides) and peptide GPFPLEMTLGPT negatively charged (anionic),
whereas the rest are neutral. The identified peptides had high hydrophobicity
ratio and low molecular weights with amino acids sequences ranging from 5 to 12
residues. The mode of action of these peptides is observed under the scanning
electron microscope and is due to cell lysis of fungi. This work reveals the
potential of peptides from L. mesenteroides DU15 as natural antifungal
preservatives in inhibiting the growth of A. niger that is implicated to the
spoilage during storage.
PMID- 25847318
TI - Staging for vaginal cancer.
AB - Vaginal cancer is a rare cancer comprising about 3% of all gynecologic cancers.
Primary vaginal cancer should be carefully assigned as spread from cervix, vulva,
and other metastatic tumors to vagina can occur. Although vaginal cancer
traditionally occurs in older postmenopausal women, the incidence of high-risk
human papillomavirus (HPV)-induced cancers is increasing in younger women.
Squamous cell carcinoma is still the most common histopathologic type followed by
adenocarcinoma. With decreasing use of diethylstilbestrol in pregnancy, non
diethylstilbestrol-associated cancers are described. The Federation
Internationale de Gynecologie et d'Obstetrique (FIGO) staging of vaginal cancer
(2009) follows the same rules as cervical cancer; it is clinically staged and
allows the use of routine investigative modalities for staging. Although FIGO
encourages the use of advanced imaging modalities, such as computed tomography,
magnetic resonance imaging (MRI), and positron emission tomography (PET), to
guide therapy, the imaging findings may not be used to change or reassign the
stage. TNM staging is the pathologic staging system proposed by the American
Joint Committee on Cancer, and information available from examination of the
resected specimen, including pelvic and inguinal lymph nodes, may be used for
staging.
PMID- 25847319
TI - Patients with psoriasis have insufficient knowledge of their risk of
atherothrombotic disease and metabolic syndrome.
AB - BACKGROUND: Knowledge is crucial to allow patients to increase their level of
self-care. OBJECTIVES: To examine the extent to which patients with moderate to
severe psoriasis feel informed about their disease, to investigate their level of
knowledge about psoriasis and the associated risk of atherothrombotic disease and
metabolic syndrome, and to assess the importance of the kind of treatment
received and of membership of a patients' association. METHODS: In total, 218
patients with psoriasis (mean age 45.5 years, range 18-83), who were being
treated with methotrexate or biological drugs responded to a questionnaire.
RESULTS: Patients were well informed about their skin disease, but were less well
informed about their risk of atherothrombotic disease/metabolic syndrome (visual
analogue scale values of 6.91 and 5.15, respectively). Patients' knowledge of the
disease was reflected by 74.2-99.1% correct answers (CA). The risk of arthritis
elicited 88% CA and of depression 41.7% CA, while the risk of atherothrombotic
disease and metabolic syndrome produced only 11.9-15.3% CA. Patients treated with
biological drugs had a significantly stronger sense of being more well informed
about the risk of disease (P = 0.02) and their risks (P < 0.001) compared with
patients treated with methotrexate. Members of a patients' association had
significantly more knowledge than nonmembers about the risk of depression (P =
0.01), hypertension (P = 0.001), diabetes mellitus (P = 0.01) and obesity (P =
0.04). CONCLUSIONS: This study shows that few patients with moderate to severe
psoriasis are aware of their increased risk of atherothrombotic disease and
metabolic syndrome. This indicates the need for patients to be offered education
concerning the risk and prevention of atherothrombotic disease and metabolic
syndrome.
PMID- 25847320
TI - Expiratory positive airway pressure (EPAP) nasal device therapy: a welcome
addition to obstructive sleep apnea syndrome therapy.
PMID- 25847321
TI - The impact of obstructive sleep apnea on high-sensitivity C-reactive protein in
subjects with or without metabolic syndrome.
AB - BACKGROUND: It is unclear whether obstructive sleep apnea (OSA) is independently
associated with increased levels of the acute-phase reactant C-reactive protein
(CRP). The purpose of this study was to evaluate the relationship between OSA and
high-sensitivity CRP (hs-CRP) levels according to the presence or absence of
metabolic syndrome (MetS). METHODS: This study recruited 245 male bus drivers
from one transportation company in Taiwan. Each participant was evaluated by a
polysomnography (PSG) test, blood lipids examination, and hs-CRP. Severity of OSA
was categorized according to the apnea-hypopnea index (AHI). RESULTS: Subjects
were categorized into severe OSA group (n = 44; 17.9 %), moderate and mild OSA
group (n = 117; 47.8 %), and non-OSA group (n = 84; 34.3 %). AHI had a
significant association with hs-CRP (beta = 0.125, p = 0.009) adjusting for age,
smoking, drinking, and MetS status. Hs-CRP was elevated with severe OSA (beta =
0.533, p = 0.005) even adjusting for BMI and MetS. Moreover, there was an
independent effect for adjusted odds ratios (AORs) between the stratification of
the severity for OSA and MetS. CONCLUSION: Elevated hs-CRP level is associated
with severe OSA, independent of known confounders. The effect of OSA in CRP is
independent of MetS was identified.
PMID- 25847322
TI - Etiology and pathogenesis of the cohesinopathies.
AB - Cohesin is a chromosome-associated protein complex that plays many important
roles in chromosome function. Genetic screens in yeast originally identified
cohesin as a key regulator of chromosome segregation. Subsequently, work by
various groups has identified cohesin as critical for additional processes such
as DNA damage repair, insulator function, gene regulation, and chromosome
condensation. Mutations in the genes encoding cohesin and its accessory factors
result in a group of developmental and intellectual impairment diseases termed
'cohesinopathies.' How mutations in cohesin genes cause disease is not well
understood as precocious chromosome segregation is not a common feature in cells
derived from patients with these syndromes. In this review, the latest findings
concerning cohesin's function in the organization of chromosome structure and
gene regulation are discussed. We propose that the cohesinopathies are caused by
changes in gene expression that can negatively impact translation. The
similarities and differences between cohesinopathies and ribosomopathies,
diseases caused by defects in ribosome biogenesis, are discussed. The
contribution of cohesin and its accessory proteins to gene expression programs
that support translation suggests that cohesin provides a means of coupling
chromosome structure with the translational output of cells.
PMID- 25847323
TI - Female infertility: do we forget the thyroid?
PMID- 25847325
TI - Preexisting antigen-specific immune responses are modulated by oral KLH feeding
in humans.
AB - Oral tolerance is the antigen-specific inhibition of a systemic immune response
after oral antigen uptake and well established in animal models. We recently
showed that keyhole limpet hemocyanin (KLH) feeding modulates subsequently
induced systemic immune responses in humans as well. In the present study, we
investigated whether oral KLH can also modulate preexisting antigen-specific
systemic B- and T-cell responses. We induced delayed-type hypersensitivity (DTH)
reactions as well as systemic KLH-specific B- and T-cell responses by
subcutaneous KLH injections. Subsequent oral KLH administration decreased the
small proportion of antigen-specific CD4(+) T cells positive for the cytokine IL
17 at the end of the feeding regimen even further. After reimmunization, there
was no difference in DTH reactions and the KLH-specific B-cell responses, but KLH
fed volunteers had an increased proportion of antigen-specific CD4(+) T cells
positive for IL-10 and a reduced proportion of antigen-specific CD4(+) T cells
positive for the skin-homing receptor cutaneous lymphocyte antigen and IL-2 and
IFN-gamma. Taken together, oral KLH can modulate a preexisting systemic KLH
specific immune response. These results suggest that feeding antigen may offer
therapeutic strategies for the suppression of unwanted immune reactions in
humans.
PMID- 25847324
TI - The lung endothelin system: a potent therapeutic target with bosentan for the
amelioration of lung alterations in a rat model of diabetes mellitus.
AB - PURPOSE: The aim of this study is to show the effect of a new mechanism on
endothelin (ET) receptors in the physiopathology of diabetes-related pulmonary
injury. We tested the hypothesis that dual ET-1 receptor antagonism via bosentan
can reverse diabetes-induced lung injury. METHODS: The rats (24 male) were
separated into four groups: group 1 (HEALTHY): Control group; group 2 (DM):
Streptozotocin 60 mg/kg (i.p.); group 3 (DM + BOS-1): Diabetes + bosentan 50
mg/kg per-os; group 4 (DM + BOS-2): Diabetes + bosentan 100 mg/kg per-os. The
bosentan treatment was initiated immediately after the onset of STZ-induced
diabetes and continued for 6 weeks. RESULTS: In the treatment group, SOD activity
was significantly increased, although GSH and MDA levels and TNF-alpha and TGF
beta gene expression were decreased. Bosentan 50 mg/kg and bosentan 100 mg/kg
showed a significantly down-regulatory effect on ET-1, ET-A, and ET-B mRNA
expression. CONCLUSIONS: In conclusion, increased endothelin levels in the lung
associated with diabetes may be one cause of endothelial dysfunction, cytokine
increase, and oxidant/antioxidant imbalance in the pathogenesis of complications
that may develop during diabetes. With its multiple effects, bosentan therapy may
be an effective option against complications that may develop in association with
diabetes.
PMID- 25847326
TI - NLRP3 inflammasome is responsible for Hantavirus inducing interleukin-1beta in
THP-1 cells.
AB - Persistent high fever is one typical clinical symptom of hemorrhagic fever with
renal syndrome (HFRS) and circulating interleukin-1beta (IL-1beta) is elevated
throughout HFRS. The mechanisms responsible for viral induction of IL-1beta
secretion are unknown. In the present study, Hantaan virus (HTNV) induced the
secretion of IL-1beta in the human monocytic cell line THP-1. Induction of IL
1beta by HTNV relies on the activation of caspase-1. Small hairpin RNA knockdown
in HTNV-infected THP-1 cells indicated that nucleotide-binding domain, leucine
rich repeat containing protein 3 (NLRP3) recruits the adaptor apoptosis
associated speck-like protein and caspase-1 to form an NLRP3 inflammasome
complex, crucial for the induction of IL-1beta. In HTNV-infected THP-1 cells,
reactive oxygen species release, but not extracellular adenosine triphosphate,
was crucial for IL-1beta production. In conclusion, Hantavirus induces the
formation of the NLRP3 inflammasome in THP-1 cells and this may be responsible
for the elevated IL-1beta levels in HFRS patients.
PMID- 25847327
TI - Heterometallic 3d-4f single-molecule magnets.
AB - The promising potential applications, such as information processing and storage
or molecular spintronics, of single-molecule magnets (SMMs) have spurred on the
research of new, better SMMs. In this context, lanthanide ions have been seen as
ideal candidates for new heterometallic transition metal-lanthanide SMMs. This
perspective reviews 3d-4f SMMs up to 2014 and highlights the most significant
advances and challenges of the field.
PMID- 25847328
TI - Wild immunology.
PMID- 25847329
TI - Rationing of health care: is there an economic rationality to it?
AB - The point of departure of this Editorial is the fact that we all are engaged in
self-rationing in our everyday lives. We would like to spend more money on all
sorts of nice things and devote more time to our cherished activities. Imposed
rationing is characteristic of wartime governments, who seek to prevent the rich
from gobbling up the resources left by the army. Since the publication in 1987 of
David Callahan's Setting Limits: Medical Goals in an Aging Society (Callahan,
Setting limits: medical goals in an aging society, Simon & Schuster, New York,
1987), rationing of health care has become a widely debated issue (the Internet
is full of pertinent entries). While rationing has also been addressed by health
economists, there are three puzzling observations. First, Callahan (Callahan,
Setting limits: medical goals in an aging society, Simon & Schuster, New York,
1987) wrote for an American audience whereas rationing was introduced by the
British National Health Service (NHS) well before 1987, with little debate.
Second, the economic theory of rationing had been laid out by James Tobin
[Ectrica 20(4): 521-533, 1952] as early as 1952--but health economists seem to
have neglected his groundwork when writing about rationing. Third, they accept
government-imposed rationing as inevitable in the case of health care, as though
the self-rationing alternative was unavailable. An attempt is made here to
provide rational explanations for these puzzles.
PMID- 25847330
TI - Development of a conceptual model of health-related quality of life among
hepatitis C patients: A systematic review of qualitative studies.
AB - AIM: The Food and Drug Administration guidelines emphasize that patient-reported
outcome (PRO) instruments used in clinical trials must be developed based on a
conceptual model, yet existing PRO instruments currently used in clinical trials
of hepatitis C virus (HCV) patients are not based on a predetermined model. The
purpose of this study was to identify a comprehensive list of health-related
quality of life (HRQoL) themes that may be unique to HCV by reviewing qualitative
research articles of HCV patients. The information collected from the review was
used to develop a preliminary model of HRQoL in HCV patients. METHODS: Ovid
Medline, Ovid Embase, Ovid PsycINFO and PubMed were searched for peer-reviewed
journals from 1989 to 2012. Set inclusion/exclusion criteria were utilized with a
focus on HRQoL among HCV patients. Eligible articles that met quality assessment
criteria were analyzed using meta-synthesis to generate categories and themes to
propose a conceptual model. RESULTS: Ten articles that met the
inclusion/exclusion criteria and the quality assessment criteria were reviewed.
Eleven themes were identified: physical symptoms, physical activities, guilt,
stigma, emotional distress, psychological behavior, social relationship, social
activities, work function, sexual function and cognitive function. These were
further grouped into six HRQoL domains: physical, psychological/emotional,
social, work, sexual and cognitive functionality. CONCLUSION: The systematic
review and the proposed model represent a useful starting point in the critical
appraisal of the conceptual underpinnings of PRO instruments used in HCV
patients.
PMID- 25847331
TI - Phenotypic plasticity in gene expression contributes to divergence of locally
adapted populations of Fundulus heteroclitus.
AB - We examine the interaction between phenotypic plasticity and evolutionary
adaptation using muscle gene expression levels among populations of the fish
Fundulus heteroclitus acclimated to three temperatures. Our analysis reveals
shared patterns of phenotypic plasticity due to thermal acclimation as well as
non-neutral patterns of variation among populations adapted to different thermal
environments. For the majority of significant differences in gene expression
levels, phenotypic plasticity and adaptation operate on different suites of
genes. The subset of genes that demonstrate both adaptive differences and
phenotypic plasticity, however, exhibit countergradient variation of expression.
Thus, expression differences among populations counteract environmental effects,
reducing the phenotypic differentiation between populations. Finally, gene-by
environment interactions among genes with non-neutral patterns of expression
suggest that the penetrance of adaptive variation depends on the environmental
conditions experienced by the individual.
PMID- 25847332
TI - A personal reflection on social media in medicine: I stand, no wiser than before.
AB - Social media has enabled information, communication and reach for health
professionals. There are clear benefits to patients and consumers when health
information is broadcast. But there are unanswered questions on professionalism,
education, and the complex mentoring relationship between doctor and student.
This personal perspective raises a number of questions: What is online medical
professionalism? Can online medical professionalism be taught? Can online medical
professionalism be enforced? Is an online presence necessary to achieve the
highest level of clinical excellence? Is there evidence that social media is
superior to traditional methods of teaching in medical education? Does social
media encourage multitasking and impairment of the learning process? Are there
downsides to the perfunctory laconic nature of social media? Does social media
waste time that is better spent attaining clinical skills?
PMID- 25847333
TI - Different preparations, doses, and treatment regimens of cyclosporine A cause
adverse effects but no robust changes in seizure thresholds in rats.
AB - Neuronal transplantation is a promising experimental treatment approach for
intractable epilepsies, but rejection of porcine or human cells in rodent
epilepsy models requires adequate immunosuppression to enable long-term survival
of xenografts. The commonly used immunosuppressive drug cyclosporine A (CsA)
itself was suggested to affect seizure thresholds. However, putative pro- or
anticonvulsant effects of CsA have not yet been sufficiently explored in a direct
comparison study involving different preparations, dosages, and application
routes. We therefore comprehensively investigated the effects of acute versus
chronic treatment using different dosages (5mg/kg, 10mg/kg), application routes
(i.p., s.c.), and preparations of CsA (pure substance solved in polyethoxylated
castor oil and a ready-to-use drug additionally containing ethanol) on acute
seizure thresholds in rats in the pentylenetetrazole seizure threshold test and
verified the most harmless protocol in the chronic amygdala-kindling model for
temporal lobe epilepsy. None of the CsA treatment regimens induced acute changes
of seizure thresholds. Chronic CsA treatment also did not robustly change seizure
thresholds. As evaluated by whole blood analyses, bioavailability of CsA was
significantly higher after i.p. application of the ready-to-use preparation
compared to the pure substance and compared to s.c. APPLICATION: Observed adverse
effects differed between CsA treatment regimens and included reversible diarrhea,
lowered body temperature, and tremor, the latter two of which were also induced
by vehicle injections containing ethanol and/or polyethoxylated castor oil. Our
data suggest that chronic treatment (2 weeks) with 10mg/kg CsA injected i.p. in
the ready-to-use preparation is an appropriate protocol for use in neural
transplantation in epilepsy research applying the presently used rat models.
Transplantation studies in experimental epilepsy research require a careful
assessment of putative CsA effects on seizure thresholds in the specific
experimental settings to be used.
PMID- 25847334
TI - Retention rates of rufinamide in pediatric epilepsy patients with and without
Lennox-Gastaut Syndrome.
AB - OBJECTIVE: To evaluate the effectiveness of rufinamide (RFM) in patients with
Lennox-Gastaut Syndrome (LGS) compared to those with other epilepsy syndromes
using time to treatment failure (retention rate) as the outcome measure. METHODS:
In this retrospective cohort study, characteristics and outcomes of all patients
receiving RFM in 2009 and 2010 were recorded. The primary outcome measure was RFM
failure, defined as discontinuation of RFM or initiation of an additional
antiepileptic therapy. The secondary outcome measure was discontinuation of RFM.
Kaplan-Meier method survival curves were generated for time to RFM failure, for
all patients and by the presence or absence of Lennox Gastaut Syndrome (LGS). The
impact of age, seizure type, fast or slow drug titration, and concomitant therapy
with valproate on retention rate were evaluated using Cox regression models.
RESULTS: One hundred thirty-three patients were included, 39 (30%) of whom had
LGS. For all patients, the probability of remaining on RFM without additional
therapy was 45% at 12 months and 30% at 24 months. LGS diagnosis was an
independent predictor of time to RFM failure (HR 0.51, 95% CI 0.31-0.83), with a
median time to failure of 18 months in LGS compared to 6 months in all others
(p=0.006). CONCLUSIONS: In a broad population of children with refractory
epilepsy, around half will continue taking the medication for at least a year
without additional therapy. Patients with LGS are two times more likely to
continue RFM without additional therapy compared to those without LGS.
PMID- 25847335
TI - Improving the prescription of folate to women receiving antiepileptic drugs.
AB - In women of childbearing potential (WCP) on antiepileptic drugs (AEDs), there is
an increased risk of teratogenicity. This can potentially be reduced with folate
supplementation. We evaluated the rate of co-prescription of AEDs and folate to
WCP by non-epileptologist Neurology attendings and residents before and after an
educational intervention. During the initial 3 month survey, 54 WCP were
prescribed >=1 AEDs. Prior to the intervention, the rate of co-prescription of
AEDs and folate was 20.4%. This was higher when neurologists were prescribing
AEDs for epilepsy (34.4%) versus other disorders (0%, p=0.02). In the 3 months
following the intervention, 48 WCP received AEDs. The rate of co-prescribing
folate increased to 64.6% (p<0.001). Neurologists treating epilepsy continued to
be more likely to prescribe folate (86.4%) than neurologists treating other
conditions (46.2%, p=0.006).
PMID- 25847336
TI - Focal seizures in children with anti-NMDA receptor antibody encephalitis.
AB - OBJECTIVE: We investigated the electroclinical features of seizures occurring in
children with anti-NMDA receptor antibody encephalitis. METHODS: Clinical
features and video EEG recordings were analyzed from pediatric patients with anti
NMDA receptor antibody encephalitis at our center over a six year period.
RESULTS: We identified eight pediatric patients with anti-NMDA receptor antibody
encephalitis. Video EEG captured multiple focal seizures in four patients. Ictal
onset in all four patients consisted of a focal rhythmic sharpened 6-12Hz
activity that subsequently spread to one or both hemispheres. When there was a
clinical correlate, seizure semiology was limb posturing with or without
dyscognitive features. While background abnormalities were noted at presentation
in three cases, the initial EEG background was normal in five, including three
patients presenting with seizures. The EEG background deteriorated with clinical
progression. CONCLUSIONS: Focal seizures are common in pediatric patients with
anti-NMDA receptor antibody encephalitis and have a characteristic ictal onset
pattern. Anti-NMDA receptor antibody encephalitis should be considered in the
differential diagnosis of a child presenting with new onset focal seizures,
irrespective of the EEG background, especially if accompanied by dyskinesia,
psychiatric symptoms or impaired cognition.
PMID- 25847337
TI - Vagus nerve stimulation in children less than 3 years with medically intractable
epilepsy.
AB - OBJECTIVE: To describe the characteristics of children less than three years of
age with medically intractable epilepsy, who underwent Vagus Nerve Stimulator
(VNS) therapy at Children's Hospital of Pittsburgh between 2004 and 2011.
METHODS: Retrospective chart review. RESULTS: Seventeen patients were identified;
adequate follow-up was available for 15. Median follow up duration was 4.3 years
(1.4-10.2 years). 12/15 (80%) had a known etiology for their epilepsy. All
patients had more than 1 seizure per week prior to VNS and a history of status
epilepticus was frequent (40%, 6/15). Five patients (33%) reported improved
seizure frequency at one year after VNS. A normal MRI was associated with seizure
improvement (p=0.007). No patient had status epilepticus after VNS at one-year
follow-up. At three years after VNS, four patients had experienced status
epilepticus with only one patient experiencing multiple episodes. Complications
were seen in 2/15 (13%) patients and in 2/21 (9.5%) procedures. SIGNIFICANCE: A
normal MRI was associated with seizure improvement at one year in children less
than three years of age at the time of VNS implant. The degree of overall seizure
reduction was modest, but the frequency of status epilepticus was decreased after
VNS implant. VNS was tolerated well in this age group.
PMID- 25847338
TI - Reduction of epileptiform activity by valproic acid in a mouse model of
Alzheimer's disease is not long-lasting after treatment discontinuation.
AB - Patients with Alzheimer's disease are at increased risk for unprovoked seizures
and epilepsy compared with age-matched controls. Experimental evidence suggests
that neuronal hyperexcitability and epilepsy can be triggered by amyloid-beta
(Abeta), the main component of amyloid plaques. Previous studies demonstrated
that the administration of an anticonvulsant and histone deacetylase inhibitor,
valproic acid, leads to a long-lasting reduction in Abeta levels. Here we used an
APdE9 mouse model of Alzheimer's disease with overproduction of Abeta to assess
whether treatment with valproic acid initiated immediately after epilepsy onset
modifies the occurrence of epileptiform activity. We also analyzed whether the
effect is long-lasting and associated with antiamyloidogenesis and histone
modifications. Male APdE9 mice (15 week old) received daily intraperitoneal
injections of 30mg/kg valproic acid for 1 week. After a 3-week wash-out, the same
animals received injections of a higher dose of valproic acid (300mg/kg) daily
for 1 week. Long-term video-electroencephalography monitoring was performed prior
to, during, and after the treatments. Abeta and total histone H3 and H4
acetylation levels were measured at 1 month after the final valproic acid
treatment. While 30mg/kg valproic acid reduced spontaneous seizures in APdE9 mice
(p<0.05, chi-square), epileptiform discharges were not reduced. Administration of
300mg/kg valproic acid, however, reduced epileptiform discharges in APdE9 mice
for at least 1 week after treatment discontinuation (p<0.05, Wilcoxon test), but
there was no consistent long-term effects on epileptiform activity after
treatment withdrawal. Further, we found no long-lasting effect on Abeta levels
(p>0.05, Mann-Whitney test), only a meager increase in global acetylation of
histone H3 (p<0.05), and no effects on H4 acetylation (p>0.05). In conclusion,
valproic acid treatment of APdE9 mice at the stage when amyloid plaques are
beginning to develop and epileptiform activity is detected reduced the amount of
epileptiform activity, but the effect disappeared after treatment
discontinuation.
PMID- 25847339
TI - The recessive model of MRP2 G1249A polymorphism decrease the risk of drug
resistant in Asian Epilepsy: a systematic review and meta-analysis.
AB - ABCC2 gene polymorphisms have been shown to be associated with drug-resistant
epilepsy. However, the published results were controversial. To comprehensively
re-evaluate the association between ABCC2 gene polymorphisms and drug-resistant
epilepsy in Asian, we carried out this meta-analysis, which included eight
related studies. Studies were selected using PUBMED, Web of science, the Cochrane
database of system reviews and Embase. Pooled odds ratio (OR) with 95% confidence
interval (CI) was used to assess the association. Studies with 1302 drug
resistant cases and 1563 drug-sensitive controls were included. No significant
association was detected by combined analyses for C-24T, G-1774delG, C3972T and
G2934A. However, significant association was found in recessive model for G1249A
polymorphism (GG vs. GA+AA: OR=0.72, 95%CI=0.53-0.96, P=0.03), indicating the
recessive model of G1249A in MRP2/ABCC2 might decrease the risk of drug
resistance in Asian epilepsy.
PMID- 25847340
TI - "It's good to know": experiences of gene identification and result disclosure in
familial epilepsies.
AB - Recognition of the role of genetics in the epilepsies has increased dramatically,
impacting on clinical practice across many epilepsy syndromes. There is limited
research investigating the impact of gene identification on individuals and
families with epilepsy. While research has focused on the impact of delivering
genetic information to families at the time of diagnosis in genetic diseases more
broadly, little is known about how genetic results in epileptic diseases
influences people's lives many years after it has been conveyed. This study used
qualitative methods to explore the experience of receiving a genetic result in
people with familial epilepsy. Interviews were conducted with individuals with
familial epilepsies in whom the underlying genetic mutation had been identified.
Recorded interviews underwent thematic analysis. 20 individuals from three
families with different epilepsy syndromes and causative genes were interviewed.
Multiple generations within families were studied. The mean time from receiving
the genetic result prior to interview was 10.9 years (range 5-14 years). Three
major themes were identified: 1) living with epilepsy: an individual's experience
of the severity of epilepsy in their family influenced their view. 2) Clinical
utility of the test: participants expressed varying reactions to receiving a
genetic result. While for some it provided helpful information and relief, others
were not surprised by the finding given the familial context. Some valued the use
of genetic information for reproductive decision-making, particularly in the
setting of severely affected family members. While altruistic reasons for
participating in genetic research were discussed, participants emphasised the
benefit of participation to them and their families. 3) 'Talking about the family
genes': individuals reported poor communication between family members about
their epilepsy and its genetic implications. The results provide important
insights into the family experience of genetic epilepsies and communication
within families. This information can be used to inform the development of
guidelines for genetic result disclosure and genetic counselling for individuals
and families with epilepsies.
PMID- 25847341
TI - Lacosamide use in the treatment of refractory epilepsy in tuberous sclerosis
complex.
AB - Lacosamide (LCS) was approved by the United States Food and Drug Administration
(FDA) in 2008 as adjunctive therapy to other anti-epileptic drugs (AEDs) to treat
focal-onset seizures, with or without secondary generalization. Its role in the
treatment of epilepsy in individuals with tuberous sclerosis complex (TSC) has
yet to be determined. This study evaluates LCS treatment of focal-onset
refractory epilepsy in patients with TSC. From November 2009 to June 2014, 46 TSC
patients followed by a single neurologist were treated with LCS. Forty-eight
percent were responders (seizure reduction >=50%). No significant differences
between responders and non-responders in demographic characteristics were found.
LCS appears to be an effective and safe treatment of refractory focal onset
seizures in TSC. Determining the long-term tolerability and efficacy of LCS in
TSC patients requires additional clinical experience.
PMID- 25847342
TI - Temporopolar blurring in temporal lobe epilepsy with hippocampal sclerosis and
long-term prognosis after epilepsy surgery.
AB - PURPOSE: We conducted a retrospective study in order to investigate the clinical
significance of temporopolar grey/white matter abnormalities (GWMA) in patients
with temporal lobe epilepsy (TLE) and unilateral hippocampal sclerosis (HS) with
a long post-surgical follow-up. METHODS: The study comprised 122 consecutive
patients with medically refractory TLE and unilateral HS who underwent epilepsy
surgery and had a minimum postoperative follow-up of 5 years. Patients were
divided into two groups, based on findings of pre-surgical MRI: group 1 with GWMA
and 2 with normal signal and grey/white matter definition in temporal pole.
Demographic and clinical data were reviewed and compared between groups. RESULTS:
GWMA were found in 52.5% of patients, always ipsilateral to HS. Compared with
group 2, group 1 patients had earlier epilepsy onset (mean, 9.3 vs 14.4 years,
P=0.001), a higher occurrence of first seizure <=2 years of age (25.8% vs 10.5%,
P=0.036; OR=2.96 [95% CI=1.07-8.19]), and greater prevalence of left HS (76.6% vs
43.1%, P<0.001; OR=4.31 [95% CI=1.98-9.38]). No differences were found in gender,
presence or type of initial precipitating injury, history of secondary
generalized seizures, duration of epilepsy, seizure frequency before surgery,
neuropsychological evaluation and presence or lateralization of pre-surgical
interictal epileptiform discharges. Postoperative follow-up varied from 5 to 11.5
years (mean 7.4) and was similar in both groups (P=0.155). The proportion of
patients classified as seizure-free (Engel class I) at last follow-up in groups 1
and 2 were 73.4% and 69%, respectively (P=0.689). Similarly, the percentages of
seizure-free patients with no antiepileptic drugs at last evaluation were not
different between groups (P=0.817). In logistic regression analysis, left HS
(P=0.001; OR=4.166 [95% CI=1.86-9.34]) and age at epilepsy onset <=2 years
(P=0.047; OR=3.885 [95% CI=1.86-17.50]) were independently associated with risk
of having GWMA. CONCLUSION: GWMA are frequent findings in patients with TLE and
HS, and may help lateralize the epileptogenic zone. Our data support the
hypothesis that GWMA are caused by seizure-related insults during the critical
period of cerebral myelination. GWMA did not influence the postoperative seizure
outcome of patients with TLE and HS, even after an extended duration of post
surgical follow-up.
PMID- 25847343
TI - Cortical thickness, surface area and folding in patients with psychogenic
nonepileptic seizures.
AB - OBJECTIVE: To determine cortical thickness (CTh), cortical surface area (CSA),
curvature and sulcal depth (SD) in patients with psychogenic nonepileptic
seizures (PNES). METHODS: Freesurfer software was used to identify differences
between active and control group in Cth, CSA, curvature, and SD.
Neuropsychological tests intending to document possible frontal lobe deficit were
applied. RESULTS: We included 37 patients with PNES (age 37.3+/-13.8; female/male
31/6; age of disease onset 26.1+/-10.6; age of disease duration 11.1+/-11.1), and
37 healthy controls (age 38.4; +/-12.7; female/male 26/11). No difference in CSA
and curvature was detected between groups. Patients with PNES had increased CTh
in the left insula, left and right medial-orbitofrontal, and left lateral
orbitofrontal, and decreased CTh in the left and right precentral, right
enthorinal, and right lateral-occipital region than healthy controls. SD was
increased at the level of the left and right insula, right rostral anterior
cingulate, right posterior cingulate, and left cuneus, and reduced at the level
of the right and left medial-orbitofrontal sulci in patients with PNES compared
to healthy controls. CONCLUSION: Individuals with PNES display a distinct profile
of changes in CTh, in association with increase in SD in both insula as compared
to controls. Our results may contribute to the understanding of the
neurobiological background of PNES. Further research, to include replication of
the findings and directed to understand the role of insula is needed.
PMID- 25847344
TI - Surgical treatment for patients with symptomatic generalised seizures due to
brain lesions.
AB - OBJECT: To study the role of epilepsy surgery for patients with focal lesions who
exhibited the semiology of clinically generalised seizures. METHODS: From our
epilepsy surgery series, we identified 29 patients who underwent surgery for
seizures, including certain types of generalised seizures, according to their
ictal semiology. We systematically reviewed the brain imaging, video-EEG,
surgical operation, and pathological findings data of these patients. RESULTS:
All patients had at least one type of generalised seizure according to the
semiology; these seizures included epileptic spasms, myoclonic seizures, tonic
seizures, atonic seizures and atypical absence seizures. Eight patients had a
single type of seizure, 11 patients had two types of seizures, and 10 patients
had more than two types of seizures. In addition to symptomatic generalised
seizures, complex partial seizures were also recorded in eight patients. In 24
patients, the ictal semiology showed slight asymmetric movements in certain types
of seizures. Generalised interictal epileptic discharges were recorded in 24
patients; and generalised ictal epileptic discharges as the only EEG pattern were
recorded in 13 patients. Intracranial recording was performed in 20 patients; 10
of whom showed a rhythm of fast activities at the initiation of the seizures.
Functional hemispherectomy was performed for three patients with hemispheric
lesions. Focal resection of the epileptogenic zone was performed in 26 patients.
The resected epileptogenic zones involved a single lobe in 10 patients, two lobes
in 11 patients, and three lobes in 5 patients; the parietal lobe was the most
commonly involved lobe (in 19 cases). Scar lesions (in 17 patients) were most
commonly observed on pathological examination. At the last follow-up (mean 18+/
8.3 months, range 12-48), 17 (58.6%) patients were seizure-free. CONCLUSIONS:
Certain patients with local brain lesions can have seizures with specific types
of generalised semiology. An appropriate operation may be helpful for a portion
of these patients.
PMID- 25847345
TI - VNS for refractory status epilepticus.
AB - BACKGROUND: Our goal was to perform a systematic review of the literature on the
insertion of vagal nerve stimulators (VNS) for refractory status epilepticus
(RSE) and its impact on the control of RSE. METHODS: All articles from MEDLINE,
BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the
International Clinical Trials Registry Platform, clinicaltrials.gov (inception to
June 2014), reference lists of relevant articles, and gray literature were
searched. The strength of evidence was adjudicated using both the Oxford and
GRADE methodology by two independent reviewers (FZ and MW). RESULTS: Overall, 17
studies were identified, with 7 manuscripts and 10 meeting abstracts. A total of
28 patients were treated. In those with generalized RSE, 76% displayed cessation
of RSE with VNS insertion. In cases of focal RSE, 25% responded to VNS insertion.
Few adverse effects related to VNS insertion were described. CONCLUSIONS: We
currently cannot recommend the use of VNS for RSE. Oxford level 4, GRADE D
evidence exists to suggest improvement in seizure control with the use of urgent
VNS in generalized RSE. No comments can be made on the utility of VNS in focal
RSE. Further prospective study is warranted.
PMID- 25847346
TI - Evaluation of amygdala pathology using (11)C-methionine positron emission
tomography/computed tomography in patients with temporal lobe epilepsy and
amygdala enlargement.
AB - OBJECTIVE: The association between amygdala enlargement (AE) and temporal lobe
epilepsy (TLE) has increasingly been reported. However, the pathology of AE
remains poorly understood. The purpose of this study was to explore AE pathology
using (11)C-methionine (Met) positron emission tomography (PET)/computed
tomography (CT) in patients who have TLE with AE. MATERIALS AND METHODS: Twenty
six TLE patients with AE and 18 TLE patients without AE underwent (11)C-Met
PET/CT and magnetic resonance imaging (MRI). (11)C-Met uptake in amygdala was
evaluated by both visual inspection and semi-quantitative measurement. MRI was
assessed visually and semi-quantitatively for AE. Laterality index (LI) was
obtained by comparing the amygdala volumes of ipsilateral and contralateral
sides. The clinical course and histopathological findings of all patients were
also analyzed. RESULTS: On (11)C-Met PET/CT images, visual examination detected
increased uptake in the enlarged amygdala in 7 of 26 (27%) TLE patients with AE,
and the results were confirmed by semi-quantitative analysis. Among six TLE
patients with AE who underwent surgery, histopathology revealed neoplasms (low
grade astrocytoma and gangliocytoma) in two patients and focal cortical dysplasia
in one patient with increased (11)C-Met uptake, but non-neoplastic lesions (focal
cortical dysplasia, vacuolar degeneration, and hamartoma) in all three patients
with no increased (11)C-Met uptake. On MRI, volume of the affected amygdala was
significantly larger compared to the contralateral amygdala. LI was significantly
higher in the group with AE than in the group without AE. CONCLUSIONS: This study
revealed that some TLE patients with AE showed increased (11)C-Met uptake in the
enlarged amygdala. (11)C-Met PET/CT is potentially useful for the evaluation of
AE pathology, and may provide beneficial information for appropriate decision
making.
PMID- 25847347
TI - Sequential prefrontal lobe volume changes and cognitive dysfunctions in children
with Panayiotopoulos syndrome presenting with status epilepticus.
AB - Panayiotopoulos syndrome (PS) is usually not associated with neurodevelopmental
problems. However, neuropsychological impairments may also be present in at least
some of the patients with PS. On the other hand, several degrees of neuronal
damage due to status epilepticus (SE) may occur in the cortex. We prospectively
measured frontal and prefrontal lobe volumes using three-dimensional magnetic
resonance imaging (3D-MRI)-based volumetry in patients with PS with and without
SE. Moreover, the neuropsychological outcome in relation to the presence of SE in
children with PS is also discussed. We studied six patients with a final
diagnosis of PS, including three cases with SE and cognitive
impairments/behavioral problems (SE group) and three cases without SE (non-SE
group). Serial 3D-MRI studies were performed five times (at onset of clinical
symptoms and 1-4 years after onset) in both the SE and non-SE patients. All
patients were studied with a set of Wechsler Intelligence Scale for Children,
version III (WISC-III) or Wechsler Preschool and Primary Scale of Intelligence
tests and the Kaufman Assessment Battery for Children (K-ABC). Growth of the
frontal and prefrontal lobes was slightly decreased for some time after SE
episodes in the SE patients. Moreover, the prefrontal-to-frontal lobe volume
ratio was stagnant for some time after SE in the SE patients. The scores on the
neuropsychological tests were decreased in the SE patients. Moreover, the average
WISC and K-ABC scores in the SE group remained low and did not reach the levels
of the initial examinations. Occurrence of SE in patients with PS at least in
some patients may be associated with retarded prefrontal lobe growth, which was
related to neuropsychological problems and ultimately, neuropsychological
outcomes. Treatment management may be required to prevent SE as much as possible
to achieve optimal prognosis in PS at least in some patients.
PMID- 25847348
TI - Epilepsy in patients with malignant middle cerebral artery infarcts and
decompressive craniectomies.
AB - Patients with malignant middle cerebral artery (MCA) infarctions who have
undergone craniectomy are susceptible to the development of vascular epilepsy.
Our objective was to study the factors that might influence the occurrence of
seizures in this group of patients. MATERIALS AND METHODS: All patients who
developed malignant MCA infarction and had undergone decompressive craniectomy in
our center between November 2002 and January 2014 were evaluated. In the
subsequent follow-up, we evaluated the clinical outcomes and attempted to
identify the factors that were related to the occurrence of seizures. RESULTS: We
evaluated a total of 80 patients. The median time at which the craniectomy was
performed was 40.5h after the stroke. Seizures occurred in 47.5% of all patients.
The mortality rate within the first week was 16%, and of those who survived 53.7%
developed seizures; 9% of these seizures were acute symptomatic, and 44.8% were
remote. The median onset of remote seizures was seven months, and the majority of
these were motor seizures with generalization. Notably, the patients with
seizures exhibited longer delays from stroke to craniectomy, greater involvements
of the temporal lobe and a higher rate of post-craniectomy recanalization of the
occluded artery. Regarding the timing of the surgeries, a significantly greater
proportion of those who underwent surgery more than 42h after the stroke
developed epilepsy (p=0.004). Logistic regression revealed that only prolonged
delay (>42h) independently predicted the development of epilepsy (OR 5.166; IC
95% 1.451-18.389; p=0.011). CONCLUSIONS: More than half of patients with
malignant MCA infarcts who underwent decompressive craniectomy developed
epilepsy. The occurrence of seizures in these patients was related to the delay
to the performance of the craniectomy.
PMID- 25847349
TI - Similar PDK1-AKT-mTOR pathway activation in balloon cells and dysmorphic neurons
of type II focal cortical dysplasia with refractory epilepsy.
AB - Dysmorphic neurons and balloon cells constitute the neuropathological hallmarks
of type II focal cortical dysplasias (FCDs) with refractory epilepsy. The genesis
of these cells may be critical to the histological findings in type II FCD.
Recent work has shown enhanced activation of the mTOR cascade in both balloon
cells and dysmorphic neurons, suggesting a common pathogenesis for these two
neuropathological hallmarks. A direct comparative analysis of balloon cells and
dysmorphic neurons might identify a molecular link between balloon cells and
dysmorphic neurons. Here, we addressed whether PDK1-AKT-mTOR activation
differentiates balloon cells from dysmorphic neurons. We used
immunohistochemistry with antibodies against phosphorylated (p)-PDK1 (Ser241), p
AKT (Thr308), p-AKT (Ser473), p-mTOR (Ser2448), p-P70S6K (Thr229), and p-p70S6
kinase (Thr389) in balloon cells compared with dysmorphic neurons. Strong or
moderate staining for components of the PDK1-AKT-mTOR signaling pathway was
observed in both balloon cells and dysmorphic neurons. However, only a few
pyramidal neurons displayed weak staining in control group (perilesional
neocortex and histologically normal neocortex). Additionally, p-PDK1 (Ser241) and
p-AKT (Thr308) staining in balloon cells were stronger than in dysmorphic
neurons, whereas p-P70S6K (Thr229) and p-p70S6 kinase (Thr389) staining in
balloon cells was weaker than in dysmorphic neurons. In balloon cells, p-AKT
(Ser473) and p-mTOR (Ser2448) staining was comparable with the staining in
dysmorphic neurons. Our data support the previously suggested pathogenic
relationship between balloon cells and dysmorphic neurons concerning activation
of the PDK1-AKT-mTOR, which may play important roles in the pathogenesis of type
II FCD. Differential expression of some components of the PDK1-AKT-mTOR pathway
between balloon cells and dysmorphic neurons may result from cell-specific gene
expression.
PMID- 25847350
TI - Scopolamine-induced convulsions in fasted animals after food intake: sensitivity
of C57BL/6J mice and Sprague-Dawley rats.
AB - Food intake triggers convulsions in fasted BALB/c mice and Wistar albino rats
treated with antimuscarinic drugs, scopolamine or atropine. Inbred strain studies
have yielded considerable information regarding genetic influences on seizure
susceptibility and factors contribute to epileptogenesis in rodents. This study,
therefore, investigated sensitivity to antimuscarinic-induced seizures in
C57BL/6J mice and Sprague-Dawley rats. Food deprivation for 48h in mice and 52h
in rats did not produce strain differences in body weight loss. Fasted animals
treated i.p. with 3mg/kg scopolamine developed convulsions after food intake. The
incidence of convulsions was indifferent in comparison to BALB/c mice and Wistar
albino rats. Number of animals developing stage 5 was more and onset of
convulsions was longer in C57BL/6J mice than in BALB/c mice. Strain-related
differences in sensitivity to seizures in C57BL/6J mice may need further
evaluation for investigating genetic influences on scopolamine-induced seizures.
PMID- 25847352
TI - Should ABO-incompatible deceased liver transplantation be reconsidered?
PMID- 25847351
TI - Cardiovascular risk factors and cognitive decline in older people with type 2
diabetes.
AB - AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established
cardiovascular risk factors in the late-life cognitive decline of patients with
type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending
the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used.
Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were
determined at baseline clinics (single time measurements) and/or from serial data
recorded on a clinical management database from diagnosis until recruitment
('historical' data). Principal component analysis derived a factor, g, of general
ability from seven cognitive tests. Linear regression models of follow-up g were
adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late
life cognitive decline' was defined as scoring in the lowest tertile of '4 year
cognitive change' regression scores. Analyses controlled for age and sex.
RESULTS: A baseline history of moderate/heavy smoking (>= 10 pack-years) and a 1%
increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a
64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45;
p = 0.046) increased risk of accelerated cognitive decline, respectively. When
treated as continuous measures, higher pack-years, historical HbA1c and
historical BP emerged as significant independent predictors of 4 year decline in
g (standardised beta range -0.07 to -0.14; all p <= 0.05).
CONCLUSIONS/INTERPRETATION: Increased smoking and poorer glycaemic control (with
relatively weaker findings for BP) during the life-course were independently
associated with accelerated late-life cognitive decline. Where possible,
evaluation is warranted of these risk factors as targets for intervention to
reduce the burden of cognitive impairment in diabetes.
PMID- 25847353
TI - Personality and emotional processing: A relationship between extraversion and the
late positive potential in adolescence.
AB - Neuroticism and extraversion are multifaceted affective-laden personality traits
that have been associated with major depressive disorder (MDD). Research and
theory have argued that extraversion, and particularly its facet positive
emotionality, is specific to MDD, while neuroticism is common across
internalizing disorders. Converging evidence has suggested that MDD is associated
with reduced engagement with emotional stimuli, but it remains unclear whether
either extraversion, neuroticism, or both modulate reactivity to emotional cues.
The late positive potential (LPP) is an event-related brain potential that is
uniquely suited to assess engagement with emotional stimuli because it reflects
sustained attention toward emotional content. The current study examined the LPP
in relation to personality traits that may confer risk for depression by
examining the relationship between the LPP and both neuroticism and extraversion
in never-depressed adolescent girls. Specifically, 550 girls aged 13.5-15.5 with
no lifetime history of depression completed an emotional picture-viewing task,
and the LPP was measured in response to neutral, pleasant, and unpleasant
pictures. Personality traits were gathered via self- and informant report.
Results indicated that high extraversion was associated with a potentiated LPP to
emotional pictures-and this effect was accounted for by positive emotionality in
particular. In contrast, there was no association between the LPP and neuroticism
or its facets. The present study is one of the first to demonstrate that
extraversion is associated with variation in neural indices of emotional picture
processing, similar to what has been observed among individuals with depression
and at high risk for depression.
PMID- 25847354
TI - Differential innate immune responses of bovine peripheral blood leukocytes to
Salmonella enterica serovars Dublin, Typhimurium, and Enteritidis.
AB - The majority of Salmonella serovars cause no clinical disease in cattle, while
some are associated with severe disease. The objective of the current study was
to determine the innate immune responses of bovine peripheral blood leukocytes
exposed to Salmonella enterica serovar Dublin (bovine-specific), Salmonella
typhimurium (murine adapted, but zoonotic), and Salmonella enteritidis (poultry
host-adapted) in 3-week-old calves. All Salmonella exposures increased cell
surface CD14 and CD18 regardless of serovar. The greatest CD14 marker mean
fluorescence was in monocytes and the greatest mean fluorescent of the marker
mean was in neutrophils. Phagocytosis increased with all serovars, but was not
different among them. Neutrophils had the greatest marker mean fluorescence for
phagocytosis, with all serovars being equal. Oxidative burst increased in all
serovars compared to control cells, but were not different among the serovars.
Neutrophils and monocytes were similar in the oxidative burst, with limited
oxidative burst detected in the primarily lymphocyte population. mRNA expression
of TNF-alpha, IL-8, and IL-12, increased above the control cells whereas none of
these serovars affected mRNA expression of TLR4. TNF-alpha was greatest in S.
enterica and S. typhimurium, compared to Salmonella dublin. In contrast, IL-8 was
expressed more in S. dublin than S. typhiurium, with S. Enteriditus intermediary.
These results show while cell surface markers, phagocytosis, and oxidative burst
were largely unaffected by serovar, cytokine and chemokine expression differed
among the Salmonella serovars. It appears that internal responses of the cells
differ, rather than cell recognition, creating pathogenicity differences among of
the serovars, even in the neonate with developing immunity.
PMID- 25847355
TI - Stability and feedback levels in food web models.
AB - Neutel & Thorne (Ecology Letters, 17:651-661, June 2014) provide an approximation
for the leading eigenvalue of a food web community matrix involving coefficients
of its characteristic polynomial. Though valuably incorporating three-way species
interactions, two critical problems emerge when one considers the dimensions of
the system, calling the approach's accuracy and precision into question.
PMID- 25847356
TI - Pediatric periorificial dermatitis: clinical course and treatment outcomes in 222
patients.
AB - BACKGROUND: Periorificial dermatitis (POD) is a rosacea-like papulopustular
facial eruption most commonly reported in young adult women. Although POD has
been reported in children as young as 6 months of age, there are limited data on
the diagnosis and management of POD in pediatric cases. METHODS: All children
diagnosed with POD at the Dermatology Clinic at the University of North Carolina
at Chapel Hill between June 2002 and March 2014 were included in the current
study. Information related to demographics, associated risk factors, treatment
prescribed, adverse effects, and response to treatment were obtained from a
retrospective analysis of medical records. RESULTS: Of the 222 children
identified, 55.4% were female, 62.2% Caucasian, and the average age at
presentation to the clinic was 6.6 years. Although the etiology of POD remains
uncertain, 29.3% reported a past medical history of atopic dermatitis, 14.9%
reported a history of asthma and 58.1% reported a history of steroid use prior to
POD onset. Fifty-nine percent were seen at a clinic visit for follow-up at an
average of 3.8 months. Treatment often involved combining oral azithromycin with
topical metronidazole or sodium sulfacetamide lotion. Of the patients with
documented follow-up, 71.8% experienced complete resolution of POD. Recurrence of
POD occurred in children dependent on inhaled steroids or nebulizers. Adverse
effects were minimally noted, but included pigmentary changes (1.8%), worsening
of symptoms (1.8%), gastrointestinal upset (0.9%), irritant dermatitis (0.9%),
and xerosis (0.5%). CONCLUSION: This study discusses the clinical diagnosis and
management of POD in pediatric cases.
PMID- 25847358
TI - Erratum.
PMID- 25847357
TI - Changing profiles of pediatric epilepsy surgery candidates over time: A
nationwide single-center experience from 1990 to 2011.
AB - OBJECTIVE: Over the past decades, the number of epilepsy surgeries in children
has increased and indications for surgery have broadened. We studied the changes
in patient characteristics between 1990 and 2011 in a nationwide cohort and
related these to seizure outcome and postoperative medication status. Second, we
tried to identify predictors for seizure outcome after pediatric epilepsy
surgery. METHODS: To study changes over time, we divided this retrospective
cohort of 234 children into two consecutive time periods of 11 years, and
statistically compared the epochs in terms of patient characteristics, surgical
variables, complications, seizure outcome, and postoperative medication status.
To identify predictors of postoperative seizure freedom, we performed univariable
and multivariable logistic regression analyses. RESULTS: The number of surgeries
per year increased from an average of 5 in the first, to 16 in the past epoch.
Over time, significantly more surgeries were performed for malformations of
cortical development, and more patients underwent magnetoencephalography (MEG)
and invasive monitoring. Four percent of patients had a serious complication.
Complete seizure freedom (Engel class IA) at 2 years after surgery was achieved
in 74% of patients, which did not change significantly over time. The proportion
of patients who were free from seizures and antiepileptic medication 2 years
after surgery significantly increased from 13% to 32%. Factors predictive of
seizure recurrence were preoperative intracranial monitoring, multilobar surgery,
etiology, and longer duration of epilepsy before surgery. SIGNIFICANCE: Although
more complex cases were operated over time and medication was withdrawn earlier
after surgery, success rates at 2 years remained stable. In combination with low
complication rates, this underscores the efficacy and safety of pediatric
epilepsy surgery. It is important to consider epilepsy surgery early, as longer
duration of epilepsy increased the risk of postoperative seizure recurrence.
PMID- 25847360
TI - Prediction of Boron-Boron Triple-Bond Polymers Stabilized by Janus-Type Bis(N
heterocyclic) Carbenes.
AB - A class of polymeric compounds containing boron-boron triple bonds stabilized by
N-heterocyclic biscarbenes is proposed. Since a triply bonded B2 is related to
its third excited state, the predicted macromolecule would be composed by several
units of an electronically excited first-row homonuclear dimer. Moreover, it is
shown that the replacement of biscarbene with N2 or CO as spacers could change
the bonding profile of the boron-boron units to a cumulene-like structure. Based
on these results, different types of diboryne polymers are proposed, which could
lead to an unprecedented set of boron materials with distinct physical
properties. The novel diboryne macromolecules could be synthesized by the
reaction of Janus-type biscarbenes with tetrabromodiborane, B2 Br4 , and sodium
naphthalenide, [Na(C10 H8 )], similarly to Braunschweig's work on the room
temperature stable boron-boron triple bond compounds (Science, 2012, 336, 1420).
PMID- 25847359
TI - Inferior cerebellar peduncular lesion causes a distinct vestibular syndrome.
AB - BACKGROUND AND PURPOSE: The inferior cerebellar peduncle (ICP) contains various
fibres to and from the cerebellum relating to the integration of the
proprioceptive and vestibular functions. However, the full clinical features of
isolated unilateral ICP lesions have not been defined in humans. METHODS: Eight
consecutive patients with isolated unilateral ICP lesions at the pontine level
(six with stroke, one with multiple sclerosis and one with brainstem
encephalitis) received bedside neurological and neuro-otological evaluations and
underwent laboratory tests including measurements of the subjective visual
vertical (SVV) and ocular torsion, bithermal caloric tests and pure tone
audiometry. RESULTS: All patients developed isolated acute vestibular syndrome
(AVS) with ipsilesional spontaneous nystagmus (n = 7) and contralesional ocular
tilt reaction (OTR) and/or SVV tilt (n = 7). In view of the normal head impulse
test in all patients and skew deviation in one, our patients met the criteria for
AVS from central lesions. Five patients showed a directional dissociation between
the OTR/SVV tilt and body lateropulsion that fell to the lesion side whilst the
OTR/SVVtilt was contraversive. CONCLUSIONS: A unilateral ICP lesion at the
pontine level leads to the development of isolated AVS. However, a negative head
impulse test and directional dissociation between OTR/SVV tilt and body
lateropulsion may distinguish lesions involving unilateral ICP at the pontine
level from those affecting other vestibular structures.
PMID- 25847361
TI - Effects of ditch-buried straw return on water percolation, nitrogen leaching and
crop yields in a rice-wheat rotation system.
AB - BACKGROUND: Crop residue management and nitrogen loss are two important
environmental problems in the rice-wheat rotation system in China. This study
investigated the effects of burial of straw on water percolation, nitrogen loss
by leaching, crop growth and yield. Greenhouse mesocosm experiments were
conducted over the course of three simulated cropping seasons in a rice1-wheat
rice2 rotation. RESULTS: Greater amounts of straw resulted in more water
percolation, irrespective of crop season. Burial at 20 and 35 cm significantly
reduced, but burial at 50 cm increased nitrogen leaching. Straw at 500 kg ha(-1)
reduced, but at 1000 kg ha(-1) and at 1500 kg ha(-1) straw increased nitrogen
leaching in three consecutive crop rotations. In addition, straw at 500 kg ha(-1)
buried at 35 cm significantly increased yield and its components for both crops.
CONCLUSIONS: This study suggests that N losses via leaching from the rice-wheat
rotation may be reduced by the burial of the appropriate amount of straw at the
appropriate depth. Greater amounts of buried straw, however, may promote nitrogen
leaching and negatively affect crop growth and yields. Complementary field
experiments must be performed to make specific agronomic recommendations.
PMID- 25847363
TI - Restoration of hematopoiesis in a case of myelodysplastic syndrome associated
with systemic lupus erythematosus treated with rituximab.
PMID- 25847364
TI - T2 relaxation times are increased in Skeletal muscle of DMD but not BMD patients.
AB - INTRODUCTION: Exon-skipping drugs in Duchenne muscular dystrophy (DMD) aim to
restore truncated dystrophin expression, which is present in the milder Becker
muscular dystrophy (BMD). MRI skeletal muscle T2 relaxation times as a
representation of edema/inflammation could be quantitative outcome parameters for
such trials. METHODS: We studied T2 relaxation times, adjusted for muscle fat
fraction using Dixon MRI, in lower leg muscles of DMD and BMD patients and
healthy controls. RESULTS: T2 relaxation times correlated significantly with fat
fractions in patients only (P < 0.001). After adjusting for muscle fat, T2
relaxation times were significantly increased in 6 muscles of DMD patients (P <
0.01), except for the extensor digitorum longus. In BMD, T2 relaxation times were
unchanged. CONCLUSIONS: T2 relaxation times could be a useful outcome parameter
in exon-skipping trials in DMD but are influenced by fat despite fat suppression.
This should be accounted for when using quantitative T2 mapping to investigate
edema/inflammation.
PMID- 25847367
TI - A Pandora's box of new materials-metallopolymers.
PMID- 25847362
TI - The effects of cocaine on heart rate and electrocardiogram in zebrafish (Danio
rerio).
AB - Zebrafish (Danio rerio) have been used as a model organism to explore the genetic
basis for responsiveness to addictive drugs like cocaine. However, very little is
known about how the physiological response to cocaine is mediated in zebrafish.
In the present study electrocardiograms (ECGs) were recorded from adult zebrafish
treated with cocaine. Treatment with cocaine resulted in a bell-shaped dose
response curve with a maximal change in heart rate seen using 5mg/L cocaine.
Higher doses resulted in a higher percentage of fish showing bradycardia. The
cocaine-induced tachycardia was blocked by co-treatment with propranolol, a beta
adrenergic antagonist, but potentiated by co-treatment with phentolamine, an
alpha-adrenergic antagonist. Co-treatment with atropine, a classic cholinergic
antagonist, had no effect on cocaine-induced tachycardia. Cocaine treatment of
adult fish changed the ECG of treated fish, inducing a dose-dependent increase in
QT interval after adjusting for heart rate (QTc), while not affecting the PR or
QRS intervals. The acute effects of cocaine on heart rate were examined in 5-day
old embryos to see if zebrafish might serve as a suitable model organism to study
possible links of embryonic physiological response to subsequent adult behavioral
response to the drug. Cocaine treatment of 5-day old zebrafish embryos also
resulted in a bell-shaped dose response curve, with maximal tachycardia achieved
with 10mg/L. The response in embryonic fish was thus comparable to that in adults
and raises the possibility that the effects of embryonic exposure to cocaine on
the developing cardiovascular system can be effectively modeled in zebrafish.
PMID- 25847370
TI - Defense of Cyber Infrastructures Against Cyber-Physical Attacks Using Game
Theoretic Models.
AB - The operation of cyber infrastructures relies on both cyber and physical
components, which are subject to incidental and intentional degradations of
different kinds. Within the context of network and computing infrastructures, we
study the strategic interactions between an attacker and a defender using game
theoretic models that take into account both cyber and physical components. The
attacker and defender optimize their individual utilities, expressed as sums of
cost and system terms. First, we consider a Boolean attack-defense model, wherein
the cyber and physical subinfrastructures may be attacked and reinforced as
individual units. Second, we consider a component attack-defense model wherein
their components may be attacked and defended, and the infrastructure requires
minimum numbers of both to function. We show that the Nash equilibrium under
uniform costs in both cases is computable in polynomial time, and it provides
high-level deterministic conditions for the infrastructure survival. When
probabilities of successful attack and defense, and of incidental failures, are
incorporated into the models, the results favor the attacker but otherwise remain
qualitatively similar. This approach has been motivated and validated by our
experiences with UltraScience Net infrastructure, which was built to support high
performance network experiments. The analytical results, however, are more
general, and we apply them to simplified models of cloud and high-performance
computing infrastructures.
PMID- 25847371
TI - Dissecting the phenotype of supernumerary marker chromosome 20 in a patient with
syndromic Pierre Robin sequence: combinatorial effect of gene dosage and
uniparental disomy.
AB - Clinical phenotypes in individuals with a supernumerary marker chromosome (SMC)
are mainly caused by gene dosage effects due to the genes located on the SMC. An
additional effect may result from uniparental disomy (UPD). Consequently, the
occurrence of UPD may be a confounding factor in identifying genotype-phenotype
correlations in SMC syndromes. Here, we report on a patient that illustrates this
problem; the phenotype of this patient was a consequence of a combined effect of
gene dosage and UPD. The proband showed facial dysmorphisms, growth retardation
and developmental delay. G-band karyotype of the proband's peripheral blood
showed the presence of mosaic SMC. A SNP array analysis documented maternal UPD20
and 20p duplication. It is known that maternal UPD20 causes prenatal onset growth
retardation and feeding difficulties. By contrast, duplication of 20p causes
facial dysmorphisms, micrognathia, cleft palate, developmental delay and
vertebral anomalies. Our classification of the proband's phenotype showed a
mixture of these two effects. Therefore, we suggest the routine use of genome
wide SNP array towards the detailed genotype-phenotype correlations for SMC
syndromes.
PMID- 25847372
TI - Biofilms affecting progression of mild steel corrosion by Gram positive Bacillus
sp.
AB - The biodeterioration of metals have detrimental effects on the environment with
economic implications. The deterioration of metals is of great concern to
industry. In this study, mild steel coupons which were immersed in a medium
containing Gram-positive Bacillus spp. and different nutrient sources were
compared with the control in sterile deionized water. The weight loss of the
coupons in the presence of Bacillus spp. alone was lower than the control and was
further reduced when additional carbon sources, especially fructose, were added.
The level of metal corrosion was significantly increased in the presence of
nitrate with or without bacteria. There was a significant strong correlation
between the weight loss and biofilm level (r = 0.64; p < 0.05). The addition of
nitrate and Bacillus spp. produced more biofilms on the coupons and resulted in
greater weight loss compared to that with Bacillus spp. only under the same
conditions. However, Bacillus spp. enriched with carbon sources formed less
biofilms and results in lower weight loss compared to that with Bacillus spp.
only. The production of biofilm by Bacillus spp. influences the level of metal
corrosion under different environmental conditions, thereby, supporting the
development of a preventive strategy against corrosion.
PMID- 25847373
TI - NRG Oncology/RTOG 0921: A phase 2 study of postoperative intensity-modulated
radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin
and paclitaxel for patients with endometrial cancer.
AB - BACKGROUND: The current study was conducted to assess acute and late adverse
events (AEs), overall survival (OS), pelvic failure, regional failure, distant
failure, and disease-free survival in a prospective phase 2 clinical trial of
bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy
in patients with high-risk endometrial cancer. METHODS: Patients underwent a
hysterectomy and lymph node removal, and had >=1 of the following high-risk
factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease
with any cervical stromal invasion, or known extrauterine extension confined to
the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and
29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of
radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The
primary endpoint was grade >=3 AEs occurring within the first 90 days (toxicity
was graded according to the National Cancer Institute Common Terminology Criteria
for Adverse Events [version 4.0]). RESULTS: A total of 34 patients were accrued
from November 2009 through December 2011, 30 of whom were eligible and received
study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval,
10.6%-36.0%) developed grade >=3 treatment-related nonhematologic toxicities
within 90 days; an additional 6 patients experienced grade >=3 toxicities between
90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease
free survival rate was 79.1%. No patient developed a within-field pelvic failure
and no patients with International Federation of Gynecology and Obstetrics stage
I to IIIA disease developed disease recurrence after a median follow-up of 26
months. CONCLUSIONS: Postoperative bevacizumab added to chemotherapy and pelvic
IMRT appears to be well tolerated and results in high OS rates at 2 years for
patients with high-risk endometrial carcinoma.
PMID- 25847374
TI - Treatment of Periodontal Disease with an Octenidine-based Antiseptic in HIV
positive Patients.
AB - OBJECTIVE: To evaluate the effects of a periodontal therapy with subsequent
application of an octenidine (OCT)-based antiseptic in HIV-positive patients
receiving highly active antiretroviral therapy. METHODS: HIV-positive patients
with a clinically diagnosed periodontal disease were randomly divided into two
groups (n = 30/group). Both groups initially received a periodontal therapy.
Patients in the OCT group additionally used an OCT-based mouthwash. Subgingival
plaque samples and periodontal indices were analysed prior to treatment onset as
well as one and 3 months post-treatment. RESULTS: Periodontal therapy has
resulted in a significant decrease in the values of all periodontal indices one
and 3 months following the therapy completion (P = 0.000). The effects of the two
applied therapeutic protocols differed significantly in terms of the variation in
the PBI (F = 4.617; P = 0.017) and the PD (F = 3.203; P = 0.044) value. In the
patients in the OCT group, a more pronounced decrease in the PBI and PD was noted
at 1-month follow-up as well as a greater increase in the PD value 3 months upon
treatment completion. In the OCT group, no more atypical microorganisms were
detectable 1 month post-treatment, while in the control group they were found in
34.5% of patients. CONCLUSIONS: The periodontal therapy bears good results in HIV
positive patients. Additional administration of OCT contributes to the
significant decline in the PBI and DS values and eliminates atypical
microorganisms within 1 month post-treatment. However, more favourable results
were not noted in the OCT group at the 3-month assessment.
PMID- 25847375
TI - Reply: To PMID 25420698.
PMID- 25847376
TI - Post-weaning parental care increases fitness but is not heritable in North
American red squirrels.
AB - Most empirical attempts to explain the evolution of parental care have focused on
its costs and benefits (i.e. fitness consequences). In contrast, few
investigations have been made of the other necessary prerequisite for
evolutionary change, inheritance. Here, we examine the fitness consequences and
heritability (h(2)) of a post-weaning parental care behaviour (territory
bequeathal) in a wild population of North American red squirrels. Each year, a
subset (average across all years = 19%) of reproductive females bequeathed their
territory to a dependent offspring. Bequeathing females experienced higher annual
reproductive success and did not suffer a survival cost to themselves relative to
those females retaining their territory. Bequeathing females thus realized higher
relative annual fitness [omega = 1.18 +/- 0.03 (SE)] than nonbequeathing females
[omega = 0.96 +/- 0.02 (SE)]. Additive genetic influences on bequeathal
behaviour, however, were not significantly different from 0 (h(2) = 1.9 * 10(-3);
95% highest posterior density interval = 3.04 * 10(-8) to 0.37) and, in fact,
bequeathal behaviour was not significantly repeatable (R = 2.0 * 10(-3); 95% HPD
interval = 0-0.27). In contrast, directional environmental influences were
apparent. Females were more likely to bequeath in years following low food
abundance and when food availability in the upcoming autumn was high. Despite an
evident fitness benefit, a lack of heritable genetic variance will constrain
evolution of this trait.
PMID- 25847382
TI - Rapid detection of active human cytomegalovirus infection in pregnancy using loop
mediated isothermal amplification.
AB - Understanding the association between congenital human cytomegalovirus (HCMV)
infection and active maternal HCMV infection during pregnancy is important for
maternal and neonatal healthcare. In the present study, a loop-mediated
isothermal amplification (LAMP) method was established for the detection of CMV
DNA from whole blood or amniotic fluid samples, using reverse transcription
quantitative polymerase chain reaction. The results of the present study
demonstrated that the CMV LAMP assay detection was specific for CMV DNA, whereas
it did not detect viral DNA from herpes simplex type 1 (HSV-1), HSV-2, varicella
zoster virus, HSV-6 or HSV-7. Sensitivity determination using serially-diluted
CMV glycoprotein B-containing plasmids, demonstrated that >10 copies per tube
were detectable using the CMV LAMP method. Furthermore, the detection results,
using the LAMP method for 336 whole blood samples, demonstrated that at a
threshold of 10(1)-10(4) copies per tube, the sensitivity of this method was
86.96-100%, the specificity was 97.24-100%, the positive predictive value was
76.92-100% and the negative predictive value was 99.05-100%. The results for 11
amniotic fluid samples from pregnant women with whole blood CMV-positive and 15
control amniotic fluid samples, indicated that the CMV LAMP assay was sensitive
and specific for CMV detection. In conclusion, in the present study, a CMV LAMP
method was developed, which was shown to be sensitive, specific and efficient in
the detection of HCMV infection. Furthermore, CMV LAMP is capable of detecting
active CMV infection in pregnant women. Therefore, the current study provides
novel insights into diagnostic approaches for active CMV infection in pregnant
women.
PMID- 25847383
TI - In vitro osteoclast formation and resorption of silicon-substituted
hydroxyapatite ceramics.
AB - Materials that participate in bone remodeling at the implant/tissue interface
represent a modern tissue engineering approach with the aim of balancing implant
resorption and nascent tissue formation. Silicon-substituted hydroxyapatite
(SiHA) ceramics are capable of stimulating new bone formation, but little is
known about their interaction with osteoclasts (OC). The effects of soluble
silicate and SiHA on OCs were investigated in this study. Soluble silicate below
500 MUM did not stimulate cell metabolism at 4 days or alter resorption area at 7
days on calcium phosphate discs. On sintered ceramics, OC numbers were similar on
HA, Si0.3 HA (0.5 wt % Si) and Si0.5 HA (1.2 wt % Si) after 21 days in vitro, but
actin ring sealing zone morphology on SiHA resembled that commonly found on bone
or on carbonate-substituted hydroxyapatite (CHA). Smaller and thicker actin rings
on SiHA as compared to HA were probably the result of altered surface chemistry
and solubility differences. The more stable sealing zones and increased lattice
solubility likely contributed to increased individual pit volumes observed on
Si0.5 HA. The delayed formation of OCs on Si0.5 HA (lower numbers at day 14)
excludes earlier differentiation as a possible mechanism of increased individual
OC pit volumes at later times (day 21). Materials characterization of Si
containing biomaterials remains paramount as the Si type and amounts can
subsequently impact downstream OC behaviour in a complex manner.
PMID- 25847384
TI - A functional perspective of nitazoxanide as a potential anticancer drug.
AB - Cancer is a group of diseases characterized by uncontrolled cell proliferation,
evasion of cell death and the ability to invade and disrupt vital tissue
function. The classic model of carcinogenesis describes successive clonal
expansion driven by the accumulation of mutations that eliminate restraints on
proliferation and cell survival. It has been proposed that during cancer's
development, the loose-knit colonies of only partially differentiated cells
display some unicellular/prokaryotic behavior reminiscent of robust ancient life
forms. The seeming "regression" of cancer cells involves changes within metabolic
machinery and survival strategies. This atavist change in physiology enables
cancer cells to behave as selfish "neo-endo-parasites" that exploit the tumor
stromal cells in order to extract nutrients from the surrounding
microenvironment. In this framework, it is conceivable that anti-parasitic
compounds might serve as promising anticancer drugs. Nitazoxanide (NTZ), a
thiazolide compound, has shown antimicrobial properties against anaerobic
bacteria, as well as against helminths and protozoa. NTZ has also been
successfully used to promote Hepatitis C virus (HCV) elimination by improving
interferon signaling and promoting autophagy. More compelling however are the
potential anti-cancer properties that have been observed. NTZ seems to be able to
interfere with crucial metabolic and pro-death signaling such as drug
detoxification, unfolded protein response (UPR), autophagy, anti-cytokine
activities and c-Myc inhibition. In this article, we review the ability of NTZ to
interfere with integrated survival mechanisms of cancer cells and propose that
this compound might be a potent addition to the current chemotherapeutic strategy
against cancer.
PMID- 25847385
TI - Mechanistic perspectives on cancer chemoprevention/chemotherapeutic effects of
thymoquinone.
AB - The bioactive natural products (plant secondary metabolites) are widely known to
possess therapeutic value for the prevention and treatment of various chronic
diseases including cancer. Thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone;
TQ), a monoterpene present in black cumin seeds, exhibits pleiotropic
pharmacological activities including antioxidant, anti-inflammatory, antidiabetic
and antitumor effects. TQ inhibits experimental carcinogenesis in a wide range of
animal models and has been shown to arrest the growth of various cancer cells in
culture as well as xenograft tumors in vivo. The mechanistic basis of anticancer
effects of TQ includes the inhibition of carcinogen metabolizing enzyme activity
and oxidative damage of cellular macromolecules, attenuation of inflammation,
induction of cell cycle arrest and apoptosis in tumor cells, blockade of tumor
angiogenesis, and suppression of migration, invasion and metastasis of cancer
cells. TQ shows synergistic and/or potentiating anticancer effects when combined
with clinically used chemotherapeutic agents. At the molecular level, TQ targets
various components of intracellular signaling pathways, particularly a variety of
upstream kinases and transcription factors, which are aberrantly activated during
the course of tumorigenesis.
PMID- 25847386
TI - Zirconium catalysed intermolecular hydroamination reactions of secondary amines
with alkynes.
AB - An in situ generated cationic zirconium complex stabilized by an n-butylamine
bridged bis(phenolato) ligand has been developed to catalyse hydroamination
reactions of secondary amines, which is the first example of group 4 metal based
catalysts capable of mediating intermolecular hydroamination reactions of N
aryl/alkyl amines.
PMID- 25847387
TI - Stroke Survivors' Experiences of Physical Rehabilitation: A Systematic Review of
Qualitative Studies.
AB - OBJECTIVE: To report and synthesize the perspectives, experiences, and
preferences of stroke survivors undertaking inpatient physical rehabilitation
through a systematic review of qualitative studies. DATA SOURCES: MEDLINE,
CINAHL, Embase, and PsycINFO were searched from database inception to February
2014. Reference lists of relevant publications were searched. All languages were
included. STUDY SELECTION: Qualitative studies reporting stroke survivors'
experiences of inpatient stroke rehabilitation were selected independently by 2
reviewers. The search yielded 3039 records; 95 full-text publications were
assessed for eligibility, and 32 documents (31 studies) were finally included.
Comprehensiveness and explicit reporting were assessed independently by 2
reviewers using the consolidated criteria for reporting qualitative research
framework. Discrepancies were resolved by consensus. DATA EXTRACTION: Data
regarding characteristics of the included studies were extracted by 1 reviewer,
tabled, and checked for accuracy by another reviewer. All text reported in
studies' results sections were entered into qualitative data management software
for analysis. DATA SYNTHESIS: Extracted texts were inductively coded and analyzed
in 3 phases using thematic synthesis. Nine interrelated analytical themes, with
descriptive subthemes, were identified that related to issues of importance to
stroke survivors: (1) physical activity is valued; (2) bored and alone; (3)
patient-centered therapy; (4) recreation is also rehabilitation; (5) dependency
and lack of control; (6) fostering autonomy; (7) power of communication and
information; (8) motivation needs nurturing; and (9) fatigue can overwhelm.
CONCLUSIONS: The thematic synthesis provides new insights into stroke survivors'
experiences of inpatient rehabilitation. Negative experiences were reported in
all studies and include disempowerment, boredom, and frustration. Rehabilitation
could be improved by increasing activity within formal therapy and in free time,
fostering patients' autonomy through genuinely patient-centered care, and more
effective communication and information. Future stroke rehabilitation research
should take into account the experiences and preferences of stroke survivors.
PMID- 25847388
TI - Normative Values for Grip and Pinch Strength for 6- to 19-Year-Olds.
AB - OBJECTIVES: To provide current normative data for grip and pinch strength in
children and young adults aged 6 to 19 years as well as to examine the effect of
age, sex, and hand dominance on grip and pinch strength. DESIGN: Descriptive
cross-sectional. SETTING: Two grade schools, 2 high schools, and 1 university.
PARTICIPANTS: Participants (N=1508; 741 male students and 767 female students)
aged 6 to 19 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Means
and SDs were calculated for each strength measurement (grip, tip pinch, lateral
pinch, palmar pinch) and stratified by age and sex. Analysis of covariance and 2
sample t tests were used to analyze the data. RESULTS: The analyses demonstrated
that age and sex had a significant effect on hand strength values, as evidenced
by increasing hand strength with age as well as greater hand strength in males
than in females. Hand dominance was not shown to have a significant effect on
hand strength. The results of this study were statistically significantly
different from previously published normative values, with most hand strength
values being lower than those published 28 years ago. CONCLUSIONS: Having updated
normative data are paramount for rehabilitation practitioners to compare the grip
and pinch strength of their clients with the average values to objectively assess
impairment and tracking progress. The statistical significance observed for most
data collected in this study as compared with those previously published supports
the need for continually updating normative data.
PMID- 25847389
TI - Crif1 Promotes Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells
After Irradiation by Modulating the PKA/CREB Signaling Pathway.
AB - Dysfunction of the hematopoietic microenvironment is the main obstacle
encountered during hematopoiesis reconstruction in patients with acute
hematopoietic radiation syndrome. Bone marrow mesenchymal stem cells (BM-MSCs)
play a crucial supporting role in hematopoiesis by maintaining the balance
between adipogenic and osteogenic differentiation. In this study, we found that
irradiation decreased the colony-forming efficiency of BM-MSCs and impaired the
balance between adipogenic and osteogenic differentiation. Following irradiation,
BM-MCSs became strongly predisposed to adipogenesis, as evidenced by increased
oil red O staining and elevated mRNA and protein levels of the adipogenic markers
and transcription factors PPARgamma and AP2. Overexpression of the essential
adipogenesis regulator Crif1 in BM-MSCs promoted adipogenesis after irradiation
exposure by upregulating adipogenesis-related genes, including C/EBPbeta,
PPARgamma, and AP2. We found that Crif1 promoted the phosphorylation of cAMP
response element binding protein (CREB) through direct interaction with protein
kinase A (PKA)-alpha. Phosphorylation of CREB was inhibited in Crif1-knockdown BM
MSCs even in the presence of a PKA agonist (db-cAMP) and could be suppressed in
Crif1-overexpressing BM-MSCs by a PKAalpha inhibitor (H-89). These results
suggest that Crif1 is an indispensable regulator of PKAalpha cat that modulates
the PKA/CREB signaling pathway to promote adipogenic differentiation of BM-MSCs
after irradiation.
PMID- 25847390
TI - Simple synthesis of luminescent CdSe quantum dots from ascorbic acid and selenium
dioxide.
AB - A simple, low-cost and convenient method was developed for the synthesis of
highly luminescent CdSe quantum dots (QDs) in an aqueous medium. Compared with
previous methods, this synthesis was carried out in one pot using ascorbic acid
(C6H8O6) to replace NaBH4 or N2H4.H2O as a reductant, and selenium dioxide to
replace selenium or its other hazardous, expensive and unstable compounds as a
precursor. The mechanism of CdSe QDs formation was elucidated. The influence of
various experimental variables, including refluxing time, Cd/MSA and Cd/Se molar
ratios, on the luminescent properties of the QDs were systematically
investigated. X-Ray powder diffraction and transmission electron microscopy
characterization indicated that the QDs had a pure cubic zinc-blended structure
with a spherical shape.
PMID- 25847391
TI - MGF enhances tenocyte invasion through MMP-2 activity via the FAK-ERK1/2 pathway.
AB - Tendon regeneration and healing requires tenocytes to move to the repair site
followed by proliferation and synthesis of the extracellular matrix. A novel
synthetic growth factor, mechano-growth factor (MGF), has been discovered to have
positive roles in tissue repair through the improvement of cell proliferation and
migration and the protection of cells against injury-induced apoptosis. However,
it remains unclear whether MGF has the potential to accelerate tendon repair. In
this study, using a transwell system, we found that MGF-C25E (a synthetic mechano
growth factor E peptide) significantly promotes tenocyte invasion, which was
accompanied by the increased phosphorylation of focal adhesion kinase (FAK) and
extracellular signal regulated kinase1/2 (ERK1/2) as well as the increased
activity of matrix metalloproteinases-2 (MMP-2). The MMP-2 inhibitor OA-Hy
blocked MGF-C25E-promoted tenocyte invasion. Inhibitors of FAK or ERK1/2 blocked
MGF-C25E-promoted tenocyte invasion and MMP-2 activity as well. These results
indicate that MGF-C25E promotes tenocyte invasion by increasing MMP-2 activity
via the FAK-ERK1/2 signaling pathway. Taken together, our findings provide the
first evidence that MGF-C25E enhances tenocyte invasion and indicate that it may
serve as a potential repair material for promoting the healing and regeneration
of injured tendons.
PMID- 25847392
TI - Predicting cumulative risk of disease onset by redistributing weights.
AB - We propose a simple approach predicting the cumulative risk of disease
accommodating predictors with time-varying effects and outcomes subject to
censoring. We use a nonparametric function for the coefficient of the time
varying effect and handle censoring through self-consistency equations that
redistribute the probability mass of censored outcomes to the right. The
computational procedure is extremely convenient and can be implemented by
standard software. We prove large sample properties of the proposed estimator and
evaluate its finite sample performance through simulation studies. We apply the
method to estimate the cumulative risk of developing Huntington's disease (HD)
from subjects with huntingtin gene mutation using a large collaborative HD study
data and illustrate an inverse relationship between the cumulative risk of HD and
the length of cytosine-adenine-guanine repeats in the huntingtin gene.
PMID- 25847393
TI - Identification and characterization of an imidazolium by-product formed during
the synthesis of 4-methylmethcathinone (mephedrone).
AB - 4-Methylmethcathinone (2-methylamino-1-(4-methylphenyl)propan-1-one, mephedrone)
is a psychoactive substance that has been associated with recreational use
worldwide. Analytical data related to mephedrone are abundantly available but the
characterization of by-products obtained during organic synthesis remains to be
explored. This study presents the identification of a 1,2,3,5-tetramethyl-4-(4
methylphenyl)-1H-imidazol-3-ium salt (TMMPI), which was formed during the
synthesis of mephedrone. When diethyl ether was added to the crude reaction
product, solid material precipitated from the solution. Analytical
characterization of TMMPI employed a range of analytical techniques including
chromatographic analysis in combination with various mass spectrometric detection
methods, nuclear magnetic resonance spectroscopy, and crystal structure analysis.
Additional confirmation was obtained from organic synthesis of the imidazolium by
product. When TMMPI was subjected to analysis by gas chromatography-mass
spectrometry (GC-MS), isomerization and degradation into two distinct compounds
were observed, which pointed towards thermal instability under GC conditions. A
liquid chromatography-mass spectrometry (LC-MS) based investigation into a micro
scale synthesis of mephedrone and three additional analogues revealed that the
corresponding TMMPI analogue was formed. Interestingly, storage of mephedrone
freebase in a number of organic solvents also gave rise to TMMPI and it appeared
that its formation during storage was significantly reduced in the absence of
air. The present study aimed to support clandestine forensic investigations by
employing analytical strategies that are applicable to manufacturing sites. The
imidazolium salts will most likely be found amongst the waste products of any
clandestine lab site under investigation rather than with the desired product.
PMID- 25847394
TI - Toxocariasis: An unusual cause of pleural effusion.
AB - Toxocara canis, one of the most frequent parasites worldwide, rarely triggers
respiratory symptoms. We report the case of a 5-year-old girl hospitalized for a
unilateral eosinophilic pleural effusion due to Toxocara canis. Besides the fact
that she was living in a squat, no other medical condition was reported. There
was no other site of infection caused by the parasite and she was successfully
treated with albendazole. This case report is obviously unique as very few cases
of pleural effusion due to Toxocara canis are reported in literature, all in
adult patients.
PMID- 25847395
TI - Roles of lymphocyte Kv1.3-channels in gut mucosal immune system: Novel
therapeutic implications for inflammatory bowel disease.
AB - In the gastrointestinal mucosal immune system, T-lymphocytes are activated to
produce pro-inflammatory cytokines, and the over-activation of the lymphocytes is
primarily responsible for the development of inflammatory bowel disease (IBD).
Despite our understanding of the molecular involvement in the activation of
lymphocytes, we know little about the physiological involvement. Circulating T
lymphocytes or those derived from thymus predominantly express delayed rectifier
K(+)-channels (Kv1.3) in their plasma membranes and these channels play crucial
roles in inducing the lymphocyte activation and proliferation. In the
pathogenesis of chronic renal failure, these channels, which are overexpressed in
proliferating lymphocytes within the kidneys, are responsible for the progression
of the disease. Since the over-activation of cellular immunity is also involved
in the pathogenesis of IBD, T-lymphocytes in the gastrointestinal mucosa could
share the same stimulatory mechanisms with those in the inflamed kidneys.
Therefore, we hypothesize here that T-lymphocytes in the gastrointestinal mucosa
would also be stimulated by the activation of the Kv1.3-channels expressed in
their plasma membranes, and that the overexpression of the channels would
contribute to the development of IBD. Our hypothesis is unique because it sheds
light for the first time on a physiological mechanism by which T-lymphocytes are
activated in the gut mucosal immune system. It is also important because our idea
could have novel therapeutic implications for IBD, in which the over-activation
of the lymphocytes is responsible for the pathogenesis.
PMID- 25847396
TI - [Cognitive and affective theory of mind in Lewy body dementia: A preliminary
study].
AB - INTRODUCTION: 'Theory of Mind' refers to the ability to attribute mental states,
thoughts (cognitive component) or feelings (affective component), to others. This
function has been studied in many neurodegenerative diseases; however, to our
knowledge no studies investigating theory of mind in dementia with Lewy Bodies
(DLB) have been published. The aim of our study was to search theory of mind
deficits in patients with DLB. METHODS: Seven patients with DLB (DLB group), at
the stage of mild dementia or mild cognitive impairments, and seven healthy
elderly adults (control group) were included in the study. After a global
cognitive assessment, we used the Faux Pas Recognition test to assess the
cognitive component of theory of mind, and the Reading the Mind in the Eyes test
for the assessment of affective component. RESULTS: We found a significant
difference between the two groups for the Faux Pas test with an average score of
35.6 for the DLB group and 48.3 for the control group (P=0.04). Scores were
particularly low in the DLB group for the last question of the test concerning
empathy (42.9% versus 85%, P=0.01). There was not a significant difference
between the two groups for the Reading the Mind in the Eyes test (P=0.077).
DISCUSSION: This preliminary study showed early impairments of theory of mind in
the DLB. The cognitive component seems more affected than the affective component
in this pathology. This pattern is consistent with the pattern found in
Parkinson's disease, but differs from other neurodegenerative diseases as
Alzheimer's disease or frontotemporal lobe dementia. These patterns may help to
differentiate DLB from these diseases. Further study is needed to confirm these
results and to compare with other dementias.
PMID- 25847397
TI - [Mnesic disorders caused by left temporal gliomas].
AB - Episodic memory disorders are frequent in patients with temporal lesion. Verbal
or visuo-spatial memory disorders depend on the location and the lateralization
of the lesion. These disorders are well described in temporal epilepsy but rarely
in population with cerebral tumor and especially not specifically focus on
temporal glioma. The purpose of this study was to describe neuropsychological
examination in patient with temporal glioma in the database of the regional
memory centre of Besancon. Four patients were identified (all right-handed and
with a left temporal glioma). Verbal episodic memory impairment and auditory
verbal short-term memory impairment were observed. One patient had also visual
memory disorders. Therefore, further investigations showed an associated
Alzheimer's disease. This finding modified the clinical management of this
patient. Extensive neuropsychological assessment should be systematic initially
to seek an associated pathology, especially in elderly patients, if the cognitive
profile is unusual, during the follow-up to better understand cognitive evolution
and the effect of therapies on cognition.
PMID- 25847398
TI - [Subcutaneous administration of levetiracetam in geriatrics].
PMID- 25847400
TI - Retinal detachment following laser retinopexy.
PMID- 25847399
TI - Quantitative proteomics of heat-treated human cells show an across-the-board mild
depletion of housekeeping proteins to massively accumulate few HSPs.
AB - Classic semiquantitative proteomic methods have shown that all organisms respond
to a mild heat shock by an apparent massive accumulation of a small set of
proteins, named heat-shock proteins (HSPs) and a concomitant slowing down in the
synthesis of the other proteins. Yet unexplained, the increased levels of HSP
messenger RNAs (mRNAs) may exceed 100 times the ensuing relative levels of HSP
proteins. We used here high-throughput quantitative proteomics and targeted mRNA
quantification to estimate in human cell cultures the mass and copy numbers of
the most abundant proteins that become significantly accumulated, depleted, or
unchanged during and following 4 h at 41 degrees C, which we define as mild heat
shock. This treatment caused a minor across-the-board mass loss in many
housekeeping proteins, which was matched by a mass gain in a few HSPs,
predominantly cytosolic HSPCs (HSP90s) and HSPA8 (HSC70). As the mRNAs of the
heat-depleted proteins were not significantly degraded and less ribosomes were
recruited by excess new HSP mRNAs, the mild depletion of the many housekeeping
proteins during heat shock was attributed to their slower replenishment. This
differential protein expression pattern was reproduced by isothermal treatments
with Hsp90 inhibitors. Unexpectedly, heat-treated cells accumulated 55 times more
new molecules of HSPA8 (HSC70) than of the acknowledged heat-inducible isoform
HSPA1A (HSP70), implying that when expressed as net copy number differences,
rather than as mere "fold change" ratios, new biologically relevant information
can be extracted from quantitative proteomic data. Raw data are available via
ProteomeXchange with identifier PXD001666.
PMID- 25847401
TI - Effect of branched-chain amino acid supplementation on functional liver
regeneration in patients undergoing portal vein embolization and sequential
hepatectomy: a randomized controlled trial.
AB - BACKGROUND: Portal vein embolization (PVE) can decrease the resection ratio for
major hepatectomy. (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy is
useful for evaluating quantitative functional liver volume. Branched chain amino
acids (BCAAs) modulate liver function and regeneration. We analyzed the effects
of BCAAs, in terms of liver function and regeneration after PVE, in combination
with major hepatectomy. METHODS: This randomized controlled trial was conducted
for patients receiving PVE through to complete hepatectomy from September, 2011
to June, 2013. BCAA granules were added two times a day to a conventional diet in
the BCAA administration group (BCAA group). The primary end point was functional
liver regeneration of the future remnant liver after PVE followed by hepatic
resection. Functional liver regeneration was assessed by the liver uptake value
obtained from (99m)Tc-GSA scintigraphy single-photon-emission computed
tomography/computed tomography fusion images. The secondary end points were
volumetric liver regeneration and changes in liver function and laboratory data.
RESULTS: A BCAA group (n = 13) and a non-BCAA group (control group; n = 15) were
included. The primary end point was partially met: the liver uptake value
significantly increased in the BCAA group compared with the control group 6
months after hepatic resection (266.7% vs 77.6%, P = 0.04) and marginally
increased after PVE (43.8% vs 17.4%, P = 0.079). Following PVE, the increment of
the uptake ratio of the liver to the liver plus heart at 15 min was significantly
less in the BCAA group than in the control group (0.0 and 0.01, P = 0.023).
CONCLUSIONS: BCAA supplementation improved functional liver regeneration and
function in patients undergoing PVE followed by major hepatic resection.
PMID- 25847402
TI - Discovery and pharmacological characterization of a novel potent inhibitor of
diacylglycerol-sensitive TRPC cation channels.
AB - BACKGROUND AND PURPOSE: The cation channel transient receptor potential canonical
(TRPC) 6 has been associated with several pathologies including focal segmental
glomerulosclerosis, pulmonary hypertension and ischaemia reperfusion-induced lung
oedema. We set out to discover novel inhibitors of TRPC6 channels and investigate
the therapeutic potential of these agents. EXPERIMENTAL APPROACH: A library of
potential TRPC channel inhibitors was designed and synthesized. Activity of the
compounds was assessed by measuring intracellular Ca(2+) levels. The lead
compound SAR7334 was further characterized by whole-cell patch-clamp techniques.
The effects of SAR7334 on acute hypoxic pulmonary vasoconstriction (HPV) and
systemic BP were investigated. KEY RESULTS: SAR7334 inhibited TRPC6, TRPC3 and
TRPC7-mediated Ca(2+) influx into cells with IC50 s of 9.5, 282 and 226 nM,
whereas TRPC4 and TRPC5-mediated Ca(2+) entry was not affected. Patch-clamp
experiments confirmed that the compound blocked TRPC6 currents with an IC50 of
7.9 nM. Furthermore, SAR7334 suppressed TRPC6-dependent acute HPV in isolated
perfused lungs from mice. Pharmacokinetic studies of SAR7334 demonstrated that
the compound was suitable for chronic oral administration. In an initial short
term study, SAR7334 did not change mean arterial pressure in spontaneously
hypertensive rats (SHR). CONCLUSIONS AND IMPLICATIONS: Our results confirm the
role of TRPC6 channels in hypoxic pulmonary vasoregulation and indicate that
these channels are unlikely to play a major role in BP regulation in SHR. SAR7334
is a novel, highly potent and bioavailable inhibitor of TRPC6 channels that opens
new opportunities for the investigation of TRPC channel function in vivo.
PMID- 25847404
TI - Current understanding of the pathogenesis of autoimmune inner ear disease: a
review.
AB - BACKGROUND: Autoimmune inner ear disease (AIED) is a poorly understood form of
sensorineural hearing loss that causes bilateral, asymmetric, progressive hearing
loss, sometimes with vestibular symptoms, often associated with a systemic
autoimmune disease, which is noteworthy as the only sensorineural loss responsive
to medical therapy. Despite much research interest of the past 25 years, its
aetiopathogenesis is still unproven. OBJECTIVE OF REVIEW: To succinctly
consolidate research and opinion regarding the pathogenesis of autoimmune inner
ear disease, in ongoing efforts to elucidate the molecular and intracellular
pathways that lead to inner ear damage, which may identify new targets for
pharmacotherapy. TYPE OF REVIEW: Systematic review SEARCH STRATEGY:
PubMed/MEDLINE search using key terms to identify articles published between
January 1980 and Apr 2014. Additionally, any landmark works discussed in this
body of literature were obtained and relevant information extracted as necessary.
EVALUATION METHOD: Inclusion criterion was any information from animal or human
studies with information relevant to possible aetiopathogenesis of AIED. Studies
that focused on diagnosis, ameliorating symptoms or treatment, without specific
information relevant to mechanisms of immune-mediated injury were excluded from
this work. Articles meeting the inclusion criteria were digested and summarised.
RESULTS: A proposed pathogenic mechanism of AIED involves inflammation and immune
mediated attack of specific inner ear structures, leading to an excessive Th1
immune response with vascular changes and tissue damage in the cochlea. Studies
have identified self-reactive T cells and immunoglobulins, and have variously
implicated immune-complex deposition, microthrombosis and electrochemical
disturbances causing impaired neurosignalling in the pathogenesis of AIED.
Research has also demonstrated abnormalities in the cytokine milieu in subjects
with AIED, which may prove a target for therapy in the future. CONCLUSION:
Ongoing research is needed to further elucidate the aetiopathogenesis of AIED and
discern between various mechanisms of tissue injury. Large-cohort clinical
studies employing IL-1 receptor blockade are warranted to determine its potential
for future therapy.
PMID- 25847403
TI - Effect of addition of statins to antiviral therapy in hepatitis C virus-infected
persons: Results from ERCHIVES.
AB - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been
variably noted to affect hepatitis C virus (HCV) treatment response, fibrosis
progression, and hepatocellular carcinoma (HCC) incidence, with some having a
more potent effect than others. We sought to determine the impact of adding
statins to antiviral therapy upon sustained virological response (SVR) rates,
fibrosis progression, and HCC development among HCV-infected persons using the
Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), an
established, longitudinal, national cohort of HCV-infected veterans. Within
ERCHIVES, we identified those who received HCV treatment and a follow-up of >24
months after treatment completion. We excluded those with human immunodeficiency
virus coinfection, hepatitis B surface antigen positivity, cirrhosis, and HCC at
baseline. Our main outcomes were liver fibrosis progression measured by FIB-4
scores, SVR rates, and incident HCC (iHCC). Among 7,248 eligible subjects, 46%
received statin therapy. Statin use was significantly associated with attaining
SVR (39.2% vs. 33.3%; P < 0.01), decreased cirrhosis development (17.3% vs.
25.2%; P < 0.001), and decreased iHCC (1.2% vs. 2.6%; P < 0.01). Statins remained
significantly associated with increased odds of SVR (odds ratio = 1.44; 95%
confidence interval [CI] = 1.29, 1.61), but lower fibrosis progression rate,
lower risk of progression to cirrhosis (hazard ratio [HR] = 0.56; 95% CI = -0.50,
0.63), and of incident HCC (HR = 0.51; 95% CI = 0.34, 0.76) after adjusting for
other relevant clinical factors. CONCLUSIONS: Statin use was associated with
improved virological response (VR) rates to antiviral therapy and decreased
progression of liver fibrosis and incidence of HCC among a large cohort of HCV
positive Veterans. These data support the use of statins in patients with HCV.
PMID- 25847405
TI - Time-lapse ratios of cone excitations in natural scenes.
AB - The illumination in natural environments varies through the day. Stable
inferences about surface color might be supported by spatial ratios of cone
excitations from the reflected light, but their invariance has been quantified
only for global changes in illuminant spectrum. The aim here was to test their
invariance under natural changes in both illumination spectrum and geometry,
especially in the distribution of shadows. Time-lapse hyperspectral radiance
images were acquired from five outdoor vegetated and nonvegetated scenes. From
each scene, 10,000 pairs of points were sampled randomly and ratios measured
across time. Mean relative deviations in ratios were generally large, but when
sampling was limited to short distances or moderate time intervals, they fell
below the level for detecting violations in ratio invariance. When illumination
changes with uneven geometry were excluded, they fell further, to levels obtained
with global changes in illuminant spectrum alone. Within sampling constraints,
ratios of cone excitations, and also of opponent-color combinations, provide an
approximately invariant signal for stable surface-color inferences, despite
spectral and geometric variations in scene illumination.
PMID- 25847406
TI - Genetic deletion of the prostaglandin E2 E prostanoid receptor subtype 3 improves
anatomical and functional outcomes after intracerebral hemorrhage.
AB - Intracerebral hemorrhage (ICH) is a stroke subtype associated with high mortality
and morbidity. Following ICH, excitotoxicity and inflammation significantly
contribute to secondary brain injury and poor outcomes. Prostaglandin E2 (PGE2 )
levels rise locally with insult to the nervous system, and PGE2 is known to
modulate these processes mainly through its E prostanoid (EP) receptors, EP1-4.
EP receptor subtype 3 (EP3) is the most abundant EP receptor in the brain and we
have previously shown that signaling through the PGE2 -EP3 axis exacerbates
excitotoxicity and ischemic stroke outcomes. This study aimed to investigate the
contribution of this pathway in modulating anatomical outcomes and functional
recovery following ICH. Genetic deletion of EP3 resulted in 48.2 +/- 7.3% less
ICH-induced brain injury (P < 0.005) and improved functional recovery (P < 0.05),
as identified by neurological deficit scoring. To start investigating the
mechanisms involved in neuroprotection with impaired PGE2 -EP3 signaling,
histological staining was performed to evaluate blood and ferric iron
accumulation, neuroinflammation, blood-brain barrier dysfunction, and peripheral
neutrophil infiltration. After ICH, EP3 knockout mice demonstrated 49.5 +/- 8.8%
and 42.8 +/- 13.1% less blood (P < 0.01) and ferric iron (P < 0.05),
respectively. Furthermore, EP3 knockout mice had significantly reduced
astrogliosis, microglial activation, blood-brain barrier breakdown, and
neutrophil infiltration. Collectively, these results suggest an injurious role
for the PGE2 -EP3 signaling axis in modulating brain injury, inflammation, and
neurological functional recovery after ICH. Modulation of the PGE2 -EP3 signaling
axis may represent a putative therapeutic avenue for the treatment of ICH.
PMID- 25847407
TI - Recombinant lentivirus with enhanced expression of caudal-related homeobox
protein 2 inhibits human colorectal cancer cell proliferation in vitro.
AB - Caudal-related homeobox protein 2 (CDX2), a tumor suppressor in the adult colon,
is overexpressed under a non-cancer specific cytomegalovirus promoter in certain
tumor cells; furthermore, non-specific expression of CDX2 may result in aberrant
side effects in normal cells. The human telomerase reverse transcriptase (hTERT)
promoter is active in the majority of cancer cells but not in normal cells.
Hypoxia is a key feature of solid tumors, and targeted genes may be significantly
upregulated by five copies of hypoxia-response elements (HREs) under hypoxic
conditions. However, the effect of CDX2 overexpression, as controlled by five
copies of HREs and the hTERT promoter, on human colorectal cancer (CRC) cell
proliferation in vitro remains to be fully elucidated. In the current study, a
recombinant lentivirus containing the CDX2 gene under the control of five HREs
and the hTERT promoter was generated. An immunofluorescence assay was used to
detect CDX2 expression by the 5 HhC lentivirus, whereas an MTT assay was used to
detect the effects of CoCl2 on the viability of LoVo cells. Western blot analysis
was conducted in order to determine the relative ratios of recombinant CDX2
protein to the internal control beta-actin, following 5 HhC/LoVo cell culture
under normoxic and hypoxic conditions (100, 200, 300, 400 or 500 umol/l CoCl2)
for 24 h, then for 12, 24 or 36 h with the optimal concentration (300 umol/l) of
CoCl2. Reverse transcription polymerase chain reaction analysis was used to
determine the transcription of recombinant CDX2 mRNA following culture of 5
HhC/LoVo cells under normoxic or hypoxic conditions. Finally, a cloning assay was
used to detect the proliferative ability of 5 HhC/LoVo and 5 Hh cells. High CDX2
expression was observed in hTERT-positive LoVo cells under hypoxic conditions, an
effect which was mimicked by treatment with CoCl2 to inhibit LoVo cell
proliferation in vitro. High expression of CDX2 therefore provides a promising
strategy for the development of novel targeted treatments and gene therapy for
CRC.
PMID- 25847408
TI - Herpesviruses: interfering innate immunity by targeting viral sensing and
interferon pathways.
AB - Type I-interferon (IFN-I) induction pathway is one of the most commonly
stimulated signaling pathways in response to viral infection. During viral
infection this pathway is stimulated by various pattern-recognition receptors,
which recognize different pathogen-associated molecular patterns. The pathways
stimulated by different pattern-recognition receptors merge into common
transcription factors IRF3 and IRF7, lead to the production of IFN-I. The
secreted IFN-I stimulates JAK-STAT pathway leading to induction of interferon
stimulated genes (ISGs). The ISGs along with IFN-I create antiviral state to
eliminate the virus from host. HHV infection enhances IFN-I-mediated innate
antiviral response during both de novo infection and lytic reactivation from
latency. However, HHV developed various molecular strategies to evade the sudden
upsurge of the IFN-I and IFN-I-mediated antiviral response to establish a
successful infection. Here, we focus on IFN-I induction and signaling pathways
induced by three representative HHVs from each sub-family of HHV and strategies
acquired by these HHVs to subvert the induction of IFN-I and ISGs to evade the
host innate immunity. These fundamental understanding provides the clue for viral
targets for pharmacological manipulation to develop potential therapeutics for
broad subtypes of HHVs.
PMID- 25847409
TI - Preoperative brain natriuretic peptide and atrial arrhythmias after coronary
artery bypass graft surgery.
AB - OBJECTIVE: To assess the association of preoperative brain natriuretic peptide
with atrial arrhythmias and length of stay after cardiac surgery. DESIGN: A
retrospective data analysis. SETTING: All data were collected from patients who
underwent cardiac surgery at a single institution, an academic hospital, between
2005 and 2010. PARTICIPANTS: Patient data were collected from the authors'
institution's Perioperative Health Documentation System of cardiac surgeries.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The major findings were that
individuals with a 10-pg/mL increase in brain natriuretic peptide were 1.005 (95%
CI: 1.002, 1.009) times more likely to have an atrial arrhythmia than those with
no increase in brain natriuretic peptide. A brain natriuretic peptide value >=306
pg/mL was calculated to best predict an atrial arrhythmia. Those above the
threshold were 1.455 (95% CI: 1.087, 1.947) times more likely to have an atrial
arrhythmia than those below the threshold. Individuals above the threshold had a
median of 3 days in the intensive care unit compared to 1 day for those below the
threshold, as well as median hospital stays of 11 days for those below the
threshold. CONCLUSIONS: The results indicated that elevated brain natriuretic
peptide was associated with increased risk of atrial arrhythmias and prolonged
length of hospital stay after cardiac surgery. Identifying at-risk patients is
important to guide preventative strategies for postoperative atrial arrhythmias.
PMID- 25847410
TI - Is urinary drainage necessary in patients with thoracic epidural analgesia? A
prospective analysis: reply.
PMID- 25847411
TI - Is urinary drainage necessary in patients with thoracic epidural analgesia? A
prospective analysis.
PMID- 25847412
TI - EZ-Blocker and One-Lung Ventilation via Tracheostomy.
PMID- 25847413
TI - Quadricuspid aortic valve detected by three-dimensional transesophageal
echocardiography.
PMID- 25847414
TI - Improving the Quality and Safety as Well as Reducing the Cost for Patients
Undergoing Cardiac Surgery: Missing Some Issues?
PMID- 25847415
TI - Blood conservation strategies can be applied safely to high-risk complex aortic
surgery.
AB - OBJECTIVE: The present study aimed to evaluate the effect of blood conservation
strategies on patient outcomes after aortic surgery. DESIGN: Retrospective cohort
analysis of prospective data. SETTING: University hospital. PARTICIPANTS:
Patients undergoing thoracic aortic surgery. INTERVENTIONS: One hundred thirty
two consecutive high-risk patients (mean EuroSCORE 10.4%) underwent thoracic
aortic aneurysm or dissection repair from January 2010 to September 2011. A blood
conservation strategy (BCS) focused on limitation of hemodilution and tolerance
of perioperative anemia was used in 57 patients (43.2%); the remaining 75 (56.8%)
patients were managed by traditional methods. Mortality, major complications, and
red blood cell transfusion requirements were assessed. Independent risk factors
for clinical outcomes were determined by multivariate analyses. MEASUREMENTS AND
MAIN RESULTS: Hospital mortality was 9.8% (13 of 132). Lower preoperative
hemoglobin was an independent predictor of mortality (p<0.01, odds ratio [OR]
1.7). Major complications were associated with perioperative transfusion: 0%
complication rate in patients receiving<2 units of packed red blood cells versus
32.3% (20 of 62) in patients receiving >=2 units. The blood conservation strategy
had no significant impact on mortality (p = 0.4) or major complications (p = 0.9)
despite the blood conservation patients having a higher incidence of aortic
dissection and urgent/emergent procedures and lower preoperative and discharge
hemoglobin. In patients with aortic aneurysms, BCS patients received 1.5 fewer
units of red blood cells (58% reduction) than non-BCS patients (p = 0.01).
Independent risk factors for transfusion were lower preoperative hemoglobin
(p<0.01, OR 1.5) and lack of BCS (p = 0.02, OR 3.6). CONCLUSIONS: Clinical
practice guidelines for blood conservation should be considered for high-risk
complex aortic surgery patients.
PMID- 25847416
TI - Posttraumatic stress symptoms in police staff 12-18 months after the Canterbury
earthquakes.
AB - Understanding posttraumatic stress disorder (PTSD) symptoms in police first
responders is an underdeveloped field. Using a cross-sectional survey, this study
investigated demographic and occupational characteristics, coping resources and
processes, along with first-responder roles and consequences 18 months following
a disaster. Hierarchical linear regression (N = 576) showed that greater symptom
levels were significantly positively associated with negative emotional coping
(beta = .31), a communications role (beta = .08) and distress following exposure
to resource losses (beta = .14), grotesque scenes (beta = .21), personal harm
(beta = .14), and concern for significant others (beta = .17). Optimism alone was
negatively associated (beta = -.15), with the overall model being a modest fit
(adjusted R(2) = .39). The findings highlight variables for further study in
police.
PMID- 25847417
TI - High plasma neurotensin levels in children with Prader-Willi syndrome.
AB - Prader-Willi syndrome (PWS) is an obesity-related genetic condition, most
commonly due to a paternal deletion of the chromosome 15q11-q13 region. PWS is
characterized by growth hormone deficiency, infantile hypotonia and feeding
problems, hypogenitalism/hypogonadism, increased pain threshold and thermal
instability, decreased gastric motility, and hyperphagia in childhood leading to
severe obesity. Neuro-endocrine peptides are known to influence gastric function
and pain sensation which led us to measure a specific peptide that may be
involved [i.e., neurotensin (NT)] in PWS and compared with unrelated control
siblings. Overnight fasting plasma NT levels were obtained from 23 children with
confirmed PWS (age: 8.2 +/- 2.0 years; range: 5-11 years) and 18 unaffected,
unrelated siblings (age: 8.2 +/- 2.3 years; range: 5-11 years) and measured using
Multiplex sandwich immunoassays with the Luminex magnetic-bead based platform.
Plasma NT levels were natural log-transformed and analyzed by ANOVA with
adjustments for age, gender, and body mass index (BMI). No difference was found
in plasma NT levels for gender, age or BMI or significant correlations seen with
age or BMI. Higher plasma NT levels (P < 0.001) were seen in PWS children (mean
of 626 +/- 238 pg/ml) compared with unaffected, unrelated siblings (mean of 371
+/- 236 pg/ml). Plasma levels were also higher in children with maternal disomy
15 (736 +/- 182 pg/ml) compared with those having the deletion subtype (548 +/-
247 pg/ml, P < 0.04). Although no measures for pain threshold, thermal
instability or gastric motility were performed in our study participants, higher
plasma NT levels were found in PWS children.
PMID- 25847418
TI - Organochlorine pesticide levels in the food web in rice paddies of Bueng Boraphet
wetland, Thailand.
AB - The contamination by organochlorine pesticides (OCPs) of water, sediments, rice
grains and leaves, and animals of different trophic levels, collected from rice
paddies surrounding Bueng Boraphet wetland, central Thailand, was studied during
November 2009 to February 2010. The levels of total
dichlorodiphenyltrichloroethanes (SigmaDDT) were too low to be detected in any
samples. High levels of total hexachlorocyclohexanes (SigmaHCH) and total aldrins
(SigmaALD) and low levels of total chlordanes (SigmaCHL) were detected in both
sediments and rice grains. alpha-HCH, beta-HCH, gamma-HCH, and aldrin in rice
grains exceeded the acceptable limits set by the Ministry of Public Health of
Thailand. Rice grains were at high risk of contamination due to the direct
spraying of OCPs. Fishes were contaminated with moderate levels of aldrin.
Continued surveys of pesticide contamination in water, sediments, and organisms
of each trophic level are recommended to more effectively monitor and control
agricultural pesticide usage around Bueng Boraphet wetland and to further assess
the ecological risks and impacts on human health.
PMID- 25847419
TI - Temporal and spatial assessment of river surface water quality using multivariate
statistical techniques: a study in Can Tho City, a Mekong Delta area, Vietnam.
AB - The present study is an evaluation of temporal/spatial variations of surface
water quality using multivariate statistical techniques, comprising cluster
analysis (CA), principal component analysis (PCA), factor analysis (FA) and
discriminant analysis (DA). Eleven water quality parameters were monitored at 38
different sites in Can Tho City, a Mekong Delta area of Vietnam from 2008 to
2012. Hierarchical cluster analysis grouped the 38 sampling sites into three
clusters, representing mixed urban-rural areas, agricultural areas and industrial
zone. FA/PCA resulted in three latent factors for the entire research location,
three for cluster 1, four for cluster 2, and four for cluster 3 explaining 60,
60.2, 80.9, and 70% of the total variance in the respective water quality. The
varifactors from FA indicated that the parameters responsible for water quality
variations are related to erosion from disturbed land or inflow of effluent from
sewage plants and industry, discharges from wastewater treatment plants and
domestic wastewater, agricultural activities and industrial effluents, and
contamination by sewage waste with faecal coliform bacteria through sewer and
septic systems. Discriminant analysis (DA) revealed that nephelometric turbidity
units (NTU), chemical oxygen demand (COD) and NH3 are the discriminating
parameters in space, affording 67% correct assignation in spatial analysis; pH
and NO2 are the discriminating parameters according to season, assigning
approximately 60% of cases correctly. The findings suggest a possible revised
sampling strategy that can reduce the number of sampling sites and the indicator
parameters responsible for large variations in water quality. This study
demonstrates the usefulness of multivariate statistical techniques for evaluation
of temporal/spatial variations in water quality assessment and management.
PMID- 25847420
TI - The socio-economic significance of the Turkish coastal environment for
sustainable development.
AB - The objective of this study was to estimate the contribution from the coastal
resources in the coastal region to the national economy for sustainable
development. There was no separate data base for the coastal zone so that the
contribution from the coastal resources in the coastal region to the national
economy was not evaluated. In estimating the significance of Turkish coastal
cities, indirect methods and the geographical information system were used. In
conclusion, it was found that 61.09% of the total national gross domestic product
and 50.75% of the national agricultural, 90.98% of the national fisheries, 68.19%
of the national tourism and 71.82% of the national industrial gross domestic
product came from the coastal zone. It was determined that while coastal cities
of Turkey had 28.23% of the national surface area, the coastal district had
12.96%; in other words, 21.5 million (28.04%) of the national population lived in
101.5 thousand km(2) (12.96%) of the national surface area. Approximately 44% of
the national gross domestic product comes from the top ten coastal cities.
According to the contribution ratio to the national economy of each coastal city,
these low-lying coastal cities have about $16 billion risk value. An analysis
showed that the coastal zone is very important for the national economy of Turkey
and also the pressure on the coastal zone is very high. At a time of increasing
pressures on coastal resources of Turkey, the decision-makers need the most up-to
date information on the full range of values these resources provide in order to
make decisions that best reflect the public interest.
PMID- 25847422
TI - The impact of chronic Aflatoxin B1 exposure and p53 genotype on base excision
repair in mouse lung and liver.
AB - Aflatoxin B1 (AFB1) is produced by species of Aspergillus, and is a known human
carcinogen. AFB1-induced oxidative DNA damage, specifically 8-hydroxy-2
deoxyguanosine (8-OHdG) lesions, has been demonstrated in both animal models and
in humans, and is repaired by base excision repair (BER). The tumour suppressor
gene p53 is implicated in the regulation of DNA repair, and heterozygous p53
knockouts have an attenuated nucleotide excision repair response to AFB1. Male
heterozygous p53 knockout mice and their wild-type controls were exposed to 0,
0.2 or 1.0ppm AFB1 for 26 weeks in their diet. BER activity of lung and liver was
assessed with an in vitro assay, using 8-OHdG-damaged plasmid DNA as a substrate.
BER activity did not differ between livers or lungs from untreated wild-type
versus heterozygous p53 knockout mice. In wild-type mice, repair was 65% lower in
liver extracts from mice exposed to 1.0ppm AFB1 than in liver extracts from mice
exposed to 0.2ppm AFB1 (p<0.05), but not significantly lower than that in liver
extracts from control mice. AFB1 did not affect BER in lung extracts from wild
type mice, or in lung and liver extracts from heterozygous p53 knockout mice. In
liver and lung, AFB1 exposure did not alter levels of 8-oxoguanine glycosylase
protein, a key enzyme in the repair of 8-OHdG, and did not cause hepatotoxicity,
as indicated by plasma alanine aminotransferase levels. In conclusion, chronic
exposure to AFB1 did not affect BER in lungs or livers of heterozygous p53
knockout mice. BER activity was lower in livers from p53 wild type mice exposed
to 1.0ppm AFB1 versus those exposed to 0.2ppm AFB1, an effect that was not
attributable to liver cell death or altered levels of 8-oxoguanine glycosylase.
PMID- 25847423
TI - Kinetoplast adaptations in American strains from Trypanosoma vivax.
AB - The mitochondrion role changes during the digenetic life cycle of African
trypanosomes. Owing to the low abundance of glucose in the insect vector (tsetse
flies) the parasites are dependent upon a fully functional mitochondrion, capable
of performing oxidative phosphorylation. Nevertheless, inside the mammalian host
(bloodstream forms), which is rich in nutrients, parasite proliferation relies on
glycolysis, and the mitochondrion is partially redundant. In this work we perform
a comparative study of the mitochondrial genome (kinetoplast) in different
strains of Trypanosoma vivax. The comparison was conducted between a West African
strain that goes through a complete life cycle and two American strains that are
mechanically transmitted (by different vectors) and remain as bloodstream forms
only. It was found that while the African strain has a complete and apparently
fully functional kinetoplast, the American T. vivax strains have undergone a
drastic process of mitochondrial genome degradation, in spite of the recent
introduction of these parasites in America. Many of their genes exhibit different
types of mutations that are disruptive of function such as major deletions,
frameshift causing indels and missense mutations. Moreover, all but three genes
(A6-ATPase, RPS12 and MURF2) are not edited in the American strains, whereas
editing takes place normally in all (editable) genes from the African strain. Two
of these genes, A6-ATPase and RPS12, are known to play an essential function
during bloodstream stage. Analysis of the minicircle population shows that its
diversity has been greatly reduced, remaining mostly those minicircles that carry
guide RNAs necessary for the editing of A6-ATPase and RPS12. The fact that these
two genes remain functioning normally, as opposed to that reported in Trypanosoma
brucei-like trypanosomes that restrict their life cycle to the bloodstream forms,
along with other differences, is indicative that the American T. vivax strains
are following a novel evolutionary pathway.
PMID- 25847421
TI - TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki)
mouse embryo fibroblasts.
AB - Somatic mutations in the tumour suppressor gene TP53 occur in more than 50% of
human tumours; in some instances exposure to environmental carcinogens can be
linked to characteristic mutational signatures. The Hupki (human TP53 knock-in)
mouse embryo fibroblast (HUF) immortalization assay (HIMA) is a useful model for
studying the impact of environmental carcinogens on TP53 mutagenesis. In an
effort to increase the frequency of TP53-mutated clones achievable in the HIMA,
we generated nucleotide excision repair (NER)-deficient HUFs by crossing the
Hupki mouse with an Xpa-knockout (Xpa-Null) mouse. We hypothesized that
carcinogen-induced DNA adducts would persist in the TP53 sequence of Xpa-Null
HUFs leading to an increased propensity for mismatched base pairing and mutation
during replication of adducted DNA. We found that Xpa-Null Hupki mice, and HUFs
derived from them, were more sensitive to the environmental carcinogen
benzo[a]pyrene (BaP) than their wild-type (Xpa-WT) counterparts. Following
treatment with the reactive metabolite of BaP, benzo[a]pyrene-7,8-diol-9,10
epoxide (BPDE), Xpa-WT and Xpa-Null HUF cultures were subjected to the HIMA. A
significant increase in TP53 mutations on the transcribed strand was detected in
Xpa-Null HUFs compared to Xpa-WT HUFs, but the TP53-mutant frequency overall was
not significantly different between the two genotypes. BPDE induced mutations
primarily at G:C base pairs, with approximately half occurring at CpG sites, and
the predominant mutation type was G:C>T:A in both Xpa-WT and Xpa-Null cells.
Further, several of the TP53 mutation hotspots identified in smokers' lung cancer
were mutated by BPDE in HUFs (codons 157, 158, 245, 248, 249, 273). Therefore,
the pattern and spectrum of BPDE-induced TP53 mutations in the HIMA are
consistent with TP53 mutations detected in lung tumours of smokers. While Xpa
Null HUFs exhibited increased sensitivity to BPDE-induced damage on the
transcribed strand, NER-deficiency did not enhance TP53 mutagenesis resulting
from damage on the non-transcribed strand in this model.
PMID- 25847424
TI - Dynamic alteration in H3 serine 10 phosphorylation is G1-phase specific during
ionization radiation induced DNA damage response in human cells.
AB - Chromatin acts as a natural barrier in DNA-damage recognition and repair.
Histones undergo differential post-translational modification(s) to facilitate
DNA damage response (DDR). Importance of modifications like phosphorylation of
histone variant H2A.X in DNA repair is very well understood, however, ambiguous
results exist in literature regarding the levels of certain histone modifications
and their possible role in repair. In the present study, we have investigated in
depth the alteration in the level of the highly dynamic histone mark H3S10P as it
plays a dual role in different phases of the cell cycle. We show here that H3S10P
decreases specifically from irradiated G1-enriched cells irrespective of the
damaging agent or the cell line used in the study. Interestingly, the loss occurs
predominantly from H3.3 variant which is a transcription activation mark like
H3S10P itself, suggesting that the alteration might be implicated in
transcription repression. The decrease in other transcription marks like H3K9Ac,
H3K14Ac, H3K56Ac and H3S28P along with the occurrence of chromatin condensation
in response to DNA damage in G1 phase strengthens the hypothesis. In addition,
the alteration in the level of H3S10P shows an inverse correlation with that of
gammaH2AX in a dose-dependent manner and probably occurs from the same
mononucleosome. We propose that the drop in the levels of histone H3S10
phosphorylation is a universal phenomenon in response to DNA damage and is a
trigger to induce transcription repressive state to facilitate repair.
PMID- 25847425
TI - More training and awareness are needed to improve the recognition of
undernutrition in hospitalised children.
AB - AIM: Reports suggest that 10% of hospitalised children in Europe are
undernourished. We investigated whether nutritional screening tools (NST) were
used in Belgian secondary-level hospitals, examined strategies for detecting
undernutrition and identified barriers preventing the systematic management of
undernutrition. METHODS: A nationwide questionnaire-based survey of paediatric
departments in Belgian secondary-level hospitals was carried out from September
2013 to February 2014. Respondents were dived into French-speaking (Walloon +
Brussels) and Dutch-speaking (Flemish) departments. RESULTS: We received replies
from 71 of the 97 (73.2%) departments. Half of the departments - 39.5% Flemish
speaking and 71.4% Walloon speaking - carried out nutritional screening.
Undernutrition was identified by measuring weight and length or height (92.7% of
cases), clinical appraisal (74.7%), mid-upper arm circumference and/or skin fold
thickness (19.7%). There was no protocol for undernutrition in many Flemish
(60.5%)- and Walloon (28.6%)-speaking departments. Reasons given for not
screening were as follows: lack of training (46.9%), ignorance of NST (42.2%) and
lack of time (29.7%). CONCLUSION: Half of the paediatric departments in Belgian
secondary-level hospitals did not carry out nutritional screening, and
differences in current practices and attitudes may be due to cultural and/or
educational differences.
PMID- 25847426
TI - A proposed food breakdown classification system to predict food behavior during
gastric digestion.
AB - The pharmaceutical industry has implemented the Biopharmaceutics Classification
System (BCS), which is used to classify drug products based on their solubility
and intestinal permeability. The BCS can help predict drug behavior in vivo, the
rate-limiting mechanism of absorption, and the likelihood of an in vitro-in vivo
correlation. Based on this analysis, we have proposed a Food Breakdown
Classification System (FBCS) framework that can be used to classify solid foods
according to their initial hardness and their rate of softening during
physiological gastric conditions. The proposed FBCS will allow for prediction of
food behavior during gastric digestion. The applicability of the FBCS framework
in differentiating between dissimilar solid foods was demonstrated using four
example foods: raw carrot, boiled potato, white rice, and brown rice. The initial
hardness and rate of softening parameter (softening half time) were determined
for these foods as well as their hypothesized FBCS class. In addition, we have
provided future suggestions as to the methodological and analytical challenges
that need to be overcome prior to widespread use and adoption of this
classification system. The FBCS gives a framework that may be used to classify
food products based on their material properties and their behavior during in
vitro gastric digestion, and may also be used to predict in vivo food behavior.
As consumer demand increases for functional and "pharma" food products, the food
industry will need widespread testing of food products for their structural and
functional performance during digestion.
PMID- 25847427
TI - Qualitative research and its methods in epilepsy: Contributing to an
understanding of patients' lived experiences of the disease.
AB - This review paper makes the case for the usefulness of qualitative research
methods in the context of epilepsy research. It begins with an assessment of the
current state of epilepsy literature and identifies gaps especially in the
following: research in 'developing' countries and research around surgery for
adults with epilepsy. It makes the case that disclosure of people's behaviors,
actions, and reactions in different, often complex health-care situations can
indicate how they bring meaning to their disease experiences and support needs.
It shows the value of encouraging work that clarifies how patients manage their
illness and how they understand changes in their health and well-being over the
life course of their illness and how health-care professionals and other
stakeholder groups care for those with epilepsy. The paper suggests a range of
methods for addressing gaps in the literature and highlights a range of data
collection, data analysis, and data interpretation and synthesis techniques that
are appropriate in this context. It pays particular attention to the strengths of
qualitative applications in mixed-methods research using an example from a recent
ulcerative colitis drug trial that indicates how they can be integrated into
study findings, add rich description, and enhance study outcomes. Ethnographic
methodology is also presented, as a way of offering rare access to the 'lived
experience' dimension, before the paper concludes with an assessment of the
qualitative criteria of credibility, dependability, transferability, and
confirmability for judging a study's 'trustworthiness'. The criteria evidence not
only the trustworthiness of data and findings but also the ways in which a study
has approached any challenges inherent in its research design.
PMID- 25847428
TI - People with epilepsy lack knowledge about their disease.
AB - For people with epilepsy, knowledge of their disease is an important factor in
optimizing the control of their seizures. Better-informed patients can more
easily participate in the treatment process, reducing disease-related anxiety and
coping better with stigma. This study was developed in a Lithuanian tertiary
epilepsy center to assess knowledge of disease among people with epilepsy, to
estimate differences in disease knowledge between patient groups, and to evaluate
how epilepsy influences patients' daily lives. We asked patients to complete a
questionnaire and collected information from outpatient cards on epilepsy
etiology, type of seizures, findings of diagnostic tests, and information about
patients' antiepileptic drugs. Our results showed that people with epilepsy have
poor knowledge about their disease: almost half of the patients did not identify
the cause of their illness or their type of seizures; most did not know the
results of their EEG and neuroimaging studies. Patients also lacked general
knowledge about their disease and implications for lifestyle. However, cognitive
deficits were not assessed in this study, and this may have affected the answers
where patients were required to recall and name their drugs or the dosage of
medication. Almost half of them believed that epilepsy had changed their lives
significantly and reported anxiety and constant fear of seizures. Patients were
also afraid to have because of the possibility they would also have epilepsy.
There is clearly a great need for improved educational intervention for people
with epilepsy.
PMID- 25847429
TI - Gender differences in social support in persons with epilepsy.
AB - The present study focused on social support as a key feature of the enhancement
and maintenance of mental health. So far, literature on gender differences in
social support and its effects on the experience of stress in individuals with
epilepsy is scarce. We hypothesized that in individuals with epilepsy, social
support buffers detrimental effects of stressors (e.g., unpredictable occurrence
of seizures) on mental health. Additionally, we explored the role of gender in
this process. In 299 individuals with epilepsy, data from validated
questionnaires on seizures in the last 3months, perceived support, social network
size, and depressive symptoms were analyzed. Women reported higher depressive
symptoms (t=2.51, p<.01) and higher perceived support (t=2.50, p<.01) than men.
Women and men did not differ in social network size (t=-0.46, p=64), nor in
experiencing seizures (chi(2)=0.07, p=.82). Regression analyses revealed no
buffer effects. Perceived support was negatively associated with depressive
symptoms (B=-0.49, p<.001, 95% CI [-0.67; -0.32]). With regard to depressive
symptoms, social integration was slightly more beneficial for women (Bcond.=
0.06, p<.001; 95% CI [-0.09; -0.03]) than for men (Bcond.=-0.02, p=.09; 95% CI [
0.04; 0.01]). Findings present perceived support and social integration as
general health resources in individuals with epilepsy regardless of previously
experienced seizures. They also encourage further research on gender-specific
effects in individuals with epilepsy and move towards recommendations for
practitioners and gender-specific interventions. Future aims will be to enhance
social integration in order to support adjustment to the chronic condition of
epilepsy and to improve individuals' confidence in support interactions.
PMID- 25847430
TI - Psychosocial factors associated with medication adherence in ethnically and
socioeconomically diverse patients with epilepsy.
AB - The current study examined psychosocial correlates of medication adherence in a
socioeconomically and racially diverse sample of patients with epilepsy. Fifty
five patients with epilepsy completed standardized self-report questionnaires
measuring depression, stress, social support, and medication and illness beliefs.
Antiepileptic drug (AED) adherence was measured using the 8-item Morisky
Medication Adherence Scale 36% reported poor adherence. We tested which
psychosocial factors were independently and most strongly associated with AED
adherence. Stress and depression were negatively correlated with adherence, while
perceived social support was positively correlated with adherence (Ps<.05). When
all three of these variables and relevant covariates in a multiple regression
model were included, only perceived social support remained a significant
predictor of adherence (P=.015). This study is one of the first to suggest the
importance of targeting social support in screening and intervention approaches
in order to improve AED adherence among low-income, racially/ethnically diverse
patients with epilepsy.
PMID- 25847431
TI - Interictal epileptiform activity and autism.
AB - Many individuals with autism have epileptiform discharges on their EEG without
having definite clinical seizures. The clinical significance of epileptiform
activity in patients with autism is controversial. Some consider it an
epiphenomenon of the underlying condition that should be ignored, and others
believe that frequent spikes may contribute to the cognitive impairment and
advocate treatment. Several studies have reported variable rates of epileptiform
activity and variable response to treatment. There is an urgent need to conduct
controlled clinical trials to assess the true incidence of epileptiform activity
in children with autism, develop a risk assessment model, and study the
effectiveness of treatment. This article is part of a Special Issue entitled
"Autism and Epilepsy".
PMID- 25847432
TI - Ductal metaplasia in oesophageal submucosal glands is associated with
inflammation and oesophageal adenocarcinoma.
AB - AIMS: Recent studies have suggested that oesophageal submucosal gland (ESMG)
ducts harbour progenitor cells that may contribute to oesophageal metaplasia. Our
objective was to determine whether histological differences exist between the
ESMGs of individuals with and without oesophageal adenocarcinoma (EAC). METHODS
AND RESULTS: We performed histological assessment of 343 unique ESMGs from 30
control patients, 24 patients with treatment-naive high-grade columnar dysplasia
(HGD) or EAC, and 23 non-EAC oesophagectomy cases. A gastrointestinal pathologist
assessed haematoxylin and eosin-stained ESMG images by using a scoring system
that assigns individual ESMG acini to five histological types (mucous, serous,
oncocytic, dilated, or ductal metaplastic). In our model, ductal metaplastic
acini were more common in patients with HGD/EAC (12.7%) than in controls (3.5%)
(P = 0.006). We also identified greater proportions of acini with dilation
(21.9%, P < 0.001) and, to a lesser extent, ductal metaplasia (4.3%, P = 0.001)
in non-EAC oesophagectomy cases than in controls. Ductal metaplasia tended to
occur in areas of mucosal ulceration or tumour. CONCLUSIONS: We found a clear
association between ductal metaplastic ESMG acini and HGD/EAC. Non-EAC cases had
dilated acini and some ductal dilation. Because ESMGs and ducts harbour putative
progenitor cells, these associations could have significance for understanding
the pathogenesis of EAC.
PMID- 25847433
TI - Preventing occupational stress in healthcare workers.
AB - BACKGROUND: Healthcare workers can suffer from occupational stress as a result of
lack of skills, organisational factors, and low social support at work. This may
lead to distress, burnout and psychosomatic problems, and deterioration in
quality of life and service provision. OBJECTIVES: To evaluate the effectiveness
of work- and person-directed interventions compared to no intervention or
alternative interventions in preventing stress at work in healthcare workers.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
(CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, NIOSHTIC-2 and Web of Science up to
November 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) of
interventions aimed at preventing psychological stress in healthcare workers. For
organisational interventions, interrupted time-series and controlled before-and
after (CBA) studies were also eligible. DATA COLLECTION AND ANALYSIS: Two review
authors independently extracted data and assessed trial quality. We used
Standardised Mean Differences (SMDs) where authors of trials used different
scales to measure stress or burnout. We combined studies that were similar in
meta-analyses. We used the GRADE system to rate the quality of the evidence. MAIN
RESULTS: In this update, we added 39 studies, making a total of 58 studies (54
RCTs and four CBA studies), with 7188 participants. We categorised interventions
as cognitive-behavioural training (CBT) (n = 14), mental and physical relaxation
(n = 21), combined CBT and relaxation (n = 6) and organisational interventions (n
= 20). Follow-up was less than one month in 24 studies, one to six in 22 studies
and more than six months in 12 studies. We categorised outcomes as stress,
anxiety or general health.There was low-quality evidence that CBT with or without
relaxation was no more effective in reducing stress symptoms than no intervention
at one month follow-up in six studies (SMD -0.27 (95% Confidence Interval (CI)
0.66 to 0.13; 332 participants). But at one to six months follow-up in seven
studies (SMD -0.38, 95% CI -0.59 to -0.16; 549 participants, 13% relative risk
reduction), and at more than six months follow-up in two studies (SMD -1.04, 95%
CI -1.37 to -0.70; 157 participants) CBT with or without relaxation reduced
stress more than no intervention.CBT interventions did not lead to a considerably
greater effect than an alternative intervention, in three studies.Physical
relaxation (e.g. massage) was more effective in reducing stress than no
intervention at one month follow-up in four studies (SMD -0.48, 95% CI -0.89 to
0.08; 97 participants) and at one to six months follow-up in six studies (SMD
0.47; 95% CI -0.70 to -0.24; 316 participants). Two studies did not find a
considerable difference in stress between massage and taking extra breaks.Mental
relaxation (e.g. meditation) led to similar stress symptom levels as no
intervention at one to six months follow-up in six studies (SMD -0.50, 95% CI
1.15 to 0.15; 205 participants) but to less stress in one study at more than six
months follow-up. One study showed that mental relaxation reduced stress more
effectively than attending a course on theory analysis and another that it was
more effective than just relaxing in a chair.Organisational interventions
consisted of changes in working conditions, organising support, changing care,
increasing communication skills and changing work schedules. Changing work
schedules (from continuous to having weekend breaks and from a four-week to a two
week schedule) reduced stress with SMD -0.55 (95% CI -0.84 to -0.25; 2 trials,
180 participants). Other organisational interventions were not more effective
than no intervention or an alternative intervention.We graded the quality of the
evidence for all but one comparison as low. For CBT this was due to the
possibility of publication bias, and for the other comparisons to a lack of
precision and risk of bias. Only for relaxation versus no intervention was the
evidence of moderate quality. AUTHORS' CONCLUSIONS: There is low-quality evidence
that CBT and mental and physical relaxation reduce stress more than no
intervention but not more than alternative interventions. There is also low
quality evidence that changing work schedules may lead to a reduction of stress.
Other organisational interventions have no effect on stress levels. More
randomised controlled trials are needed with at least 120 participants that
compare the intervention to a placebo-like intervention. Organisational
interventions need better focus on reduction of specific stressors.
PMID- 25847435
TI - Editorial: Sustainable production of renewable energy from non-food crops.
AB - Since the world faced the petroleum crisis in the 1970s and people started to
realize the limitation of fossil energy resources coupled with concerns over the
effects of increasing carbon dioxide in the atmosphere, major efforts were
devoted to the search for alternative energy sources.
PMID- 25847436
TI - More than one way to skin a cat: in-situ engineering of an antibody through photo
conjugated C2 domain.
PMID- 25847438
TI - Gender profiling: a gendered race perspective on person-position fit.
AB - The current research integrates perspectives on gendered race and person-position
fit to introduce the concept of a gender profile. We propose that both the
"gender" of a person's biological sex and the "gender" of a person's race (Asians
are perceived as feminine and Blacks as masculine) help comprise an individual's
gender profile-the overall femininity or masculinity associated with their
demographic characteristics. We also propose that occupational positions have
gender profiles. Finally, we argue that the overall gender profile of one's
demographics, rather than just one's biological sex, determines one's fit and
hirability for feminine or masculine occupational roles. The current five studies
establish the gender profiles of different races and sexes, and then demonstrate
that individuals with feminine-typed and masculine-typed gender profiles are
selected for feminine and masculine positions, respectively. These studies
provide new insights on who gets ahead in different environments.
PMID- 25847439
TI - Characterization and risk assessment of polychlorinated biphenyls in soils and
rice tissues in a suburban paddy field of the Pearl River Delta, South China.
AB - We investigated the concentration and composition of polychlorinated biphenyls
(PCBs) in paddy soils and rice tissues and the associated potential health risks
in the urban agricultural areas of the Pearl River Delta (PRD), South China. The
results indicated that highly chlorinated PCBs were more prominent in soil when
the concentrations of low-molecular-weight PCBs were relatively high in rice
plants. There was a trend of decreasing PCB concentrations with soil depth and a
significant correlation between PCBs and the total organic carbon or total
nitrogen concentration in section soils. The PCB concentrations followed the
order of root > leaf > stem > grain. Although the dioxin toxicity equivalency
values and estimated daily intake levels (based direct and indirect consumption)
were lower than in other seriously contaminated regions, there is still a need to
monitor PCB pollution in urban agriculture because of the PCB emissions from
capacitor storage following the rapid urbanization experienced in the PRD.
PMID- 25847440
TI - Effect of physical sediments reworking on hydrocarbon degradation and bacterial
community structure in marine coastal sediments.
AB - The present study aimed to examine whether the physical reworking of sediments by
harrowing would be suitable for favouring the hydrocarbon degradation in coastal
marine sediments. Mudflat sediments were maintained in mesocosms under conditions
as closer as possible to those prevailing in natural environments with tidal
cycles. Sediments were contaminated with Ural blend crude oil, and in half of
them, harrowing treatment was applied in order to mimic physical reworking of
surface sediments. Hydrocarbon distribution within the sediment and its removal
was followed during 286 days. The harrowing treatment allowed hydrocarbon
compounds to penetrate the first 6 cm of the sediments, and biodegradation
indexes (such as n-C18/phytane) indicated that biodegradation started 90 days
before that observed in untreated control mesocosms. However, the harrowing
treatment had a severe impact on benthic organisms reducing drastically the
macrofaunal abundance and diversity. In the harrowing-treated mesocosms, the
bacterial abundance, determined by 16S rRNA gene Q-PCR, was slightly increased;
and terminal restriction fragment length polymorphism (T-RFLP) analyses of 16S
rRNA genes showed distinct and specific bacterial community structure. Co
occurrence network and canonical correspondence analyses (CCA) based on T-RFLP
data indicated the main correlations between bacterial operational taxonomic
units (OTUs) as well as the associations between OTUs and hydrocarbon compound
contents further supported by clustered correlation (ClusCor) analysis. The
analyses highlighted the OTUs constituting the network structural bases involved
in hydrocarbon degradation. Negative correlations indicated the possible shifts
in bacterial communities that occurred during the ecological succession.
PMID- 25847441
TI - In search for a compromise between biodiversity conservation and human health
protection in restoration of fly ash deposits: effect of anti-dust treatments on
five groups of arthropods.
AB - Recently, fly ash deposits have been revealed as a secondary refuge of critically
endangered arthropods specialised on aeolian sands in Central Europe.
Simultaneously, these anthropogenic habitats are well known for their negative
impact on human health and the surrounding environment. The overwhelming majority
of these risks are caused by wind erosion, the substantial decreasing of which is
thus necessary. But, any effects of anti-dust treatments on endangered arthropods
have never been studied. We surveyed communities of five arthropod groups (wild
bees and wasps, leafhoppers, spiders, hoverflies and orthopteroid insects)
colonising three fly ash deposits in the western Czech Republic. We focused on
two different anti-dust treatments (~70 and 100 % cover of fly ash by barren
soil) and their comparison with a control of bare fly ash. Altogether, we
recorded 495 species, including 132 nationally threatened species (eight of them
were considered to be extinct in the country) and/or 30 species strictly
specialised to drift sands. Bees and wasps and leafhoppers contained the
overwhelming majority of species of the highest conservation interest; a few
other important records were also in spiders and orthopteroids. Total soil cover
depleted the unique environment of fly ash and thus destroyed the high
conservation potential of the deposits. On the other hand, partial coverage (with
~30 % of bare fly ash) still offered habitats for many of the most threatened
species, as we showed by both regression and multivariate analyses, with a
decrease of wind erosion. This topic still needs much more research interest, but
we consider mosaic-like preservation of smaller spots of fly ash as one of the
possible compromises between biodiversity and human health.
PMID- 25847442
TI - Sediment properties and trace metal pollution assessment in surface sediments of
the Laizhou Bay, China.
AB - Spatial distribution, ecological risk, pollutant source, and transportation of
trace metals in surface sediments, as well as the sediment properties, were
analyzed in this study to assess the pollution status of trace metal in the
Laizhou Bay, China. Results of provenance analyses indicate that surface
sediments were primarily from weathering products carried by the surrounding
short rivers and partially from loess matters carried by the Yellow River.
Variations of trace metal concentrations were mostly controlled by the
accumulation of weathering products, organic matters, and the hydrodynamics.
Geoaccumulation index suggests that no Cr pollution occurred in the study area,
and Cu, Pb, and Zn pollutions appeared only at a few stations. Comparatively, Cd
and As pollutions were at noticeably weak to moderate level at many stations. The
combination of six trace metals in this study had a 21% probability of being
toxic in our study area based on sediment quality guidelines. Enrichment factors
(EFs) and statistical analyses indicate that Cu, Pb, and Zn were primarily
derived from the natural process of weathering. By contrast, Cd, As, and Cr
(especially Cd and As) were provided by the anthropogenic activities to a large
extent. Due to the dilution of coarse-grained sediments, there was even no
contamination at some of stations that were obviously influenced by humans. Based
on the current study of transportation process of fine-grained sediments in
combination with the spatial distribution of EFs, it is found that the migration
of anthropogenic trace metals was mainly controlled by the tide in the Laizhou
Bay. The study suggests that an effective strategies and remedial measures should
be designed and undertaken to prevent further anthropogenic Cd and As pollutions
in this area in the future.
PMID- 25847443
TI - Selective oxidative degradation of toluene for the recovery of surfactant by an
electro/Fe2+/persulfate process.
AB - An electro/Fe(2+)/persulfate process has been conducted for toluene removal from
surfactant (SDS) flushing solution, and the pseudo-second-order reaction rate
constant (k2 value) of toluene removal has been optimized by a response surface
methodology (RSM). The results indicated that in this process, the reaction
between persulfate and externally added Fe(2+) generates sulfate-free radicals,
and at the same time, Fe(2+) is electro-regenerated at the cathode by the
reduction of Fe(3+). RSM based on Box-Behnken design (BBD) has been applied to
analyze the experimental variables, of which the concentrations of persulfate and
Fe(2+) showed a positive effect on the rate constant of toluene removal, whereas
the concentration of SDS showed a negative effect. The interactions between pairs
of variables proved to be significant, such as between SDS, persulfate, and
Fe(2+) concentrations. ANOVA results confirmed that the proposed models were
accurate and reliable for analysis of the variables of the
electro/Fe(2+)/persulfate process. The shapes of the 3D response surfaces and
contour plots showed that the SDS, persulfate, and Fe(2+) concentrations
substantially affected the k2 value of toluene removal. The results indicated
that increasing persulfate or Fe(2+) concentration increased the k2 value,
whereas increasing SDS concentration decreased the k2 value. The reaction
intermediates have been identified by GC-MS, and a plausible degradation pathway
for toluene degradation is proposed.
PMID- 25847444
TI - Changes in soil microbial functional diversity and biochemical characteristics of
tree peony with amendment of sewage sludge compost.
AB - A greenhouse experiment was conducted to investigate the impact of sewage sludge
compost application on functional diversity of soil microbial communities, based
on carbon source utilization, and biochemical characteristics of tree peony
(Paeonia suffruticosa). Functional diversity was estimated with incubations in
Biolog EcoPlates and well color development was used as the functional trait for
carbon source utilization. The average well color development and Shannon index
based on the carbon source utilization pattern in Biolog EcoPlates significantly
increased with the increasing sludge compost application in the range of 0-45%,
with a decreasing trend above 45%. Principal component analysis of carbon source
utilization pattern showed that sludge compost application stimulated the
utilization rate of D-cellobiose and alpha-D-lactose, while the utilization rate
of beta-methyl-D-glucoside, L-asparagine, L-serine, alpha-cyclodextrin, gamma
hydroxybutyric acid, and itaconic acid gradually increased up to a sludge compost
amendment dosage of 45% and then decreased above 45%. The chlorophyll content,
antioxidase (superoxide dismutase, catalase, and peroxidase) activities, plant
height, flower diameter, and flower numbers per plant of tree peony increased
significantly with sludge compost dosage, reaching a peak value at 45 %, and then
decreased with the exception that activity of superoxide dismutase and catalase
did not vary significantly.
PMID- 25847445
TI - Efficient secretory production of CotA-laccase and its application in the
decolorization and detoxification of industrial textile wastewater.
AB - Fungal laccases are typically unstable at high pH and temperature conditions,
which limit their application in the decolorization of textile wastewater. By
contrast, the highly stable bacterial laccases can function within a wider pH
range and at high temperatures, thus have significant potential in treatment for
textile wastewater. In our previous work, a thermo-alkali-stable CotA-laccase
gene was cloned from Bacillus pumilus W3 and overexpressed in Escherichia coli.
In this study, the robust CotA-laccase achieved efficient secretory expression in
Bacillus subtilis WB600 by screening a suitable signal peptide. A maximum CotA
laccase yield of 373.1 U/mL was obtained at optimum culture conditions in a 3-L
fermentor. Furthermore, the decolorization and detoxification of textile industry
effluent by the purified recombinant CotA-laccase in the presence and absence of
redox mediators were investigated. Among the potential mediators that enhanced
effluent decolorization, acetosyringone (ACS) was the most effective. The
toxicity of the CotA-laccase-ACS-treated effluent was greatly reduced compared
with that of the crude effluent. To the best of our knowledge, this study is the
first to report on the heterologous expression of CotA-laccase in B. subtilis.
The recombinant strain B. subtilis WB600-5 has a great potential in the
industrial production of this bacterial enzyme, and the CotA-laccase-ACS system
is a promising candidate for the biological treatment of industrial textile
effluents.
PMID- 25847446
TI - Erratum to: Innovative two-stage mesophilic/thermophilic anaerobic degradation of
sonicated sludge: performances and energy balance.
PMID- 25847447
TI - Catalytic asymmetric total synthesis of (-)-galanthamine and (-)-lycoramine.
AB - The catalytic asymmetric total syntheses of (-)-galanthamine (1) and (-)
lycoramine (2) have been achieved by using a conceptually new strategy featuring
two metal-catalyzed reactions as the key steps. A new method for the construction
of 3,4-fused benzofurans has been developed through a palladium-catalyzed
intramolecular Larock annulation reaction, which was successfully applied to the
construction of the ABD tricyclic skeleton of 1 and 2. To achieve the asymmetric
synthesis of 1 and 2, a Sc(III)/N,N'-dioxide complex was used to catalyze the
enantioselective conjugate addition of 3-alkyl-substituted benzofuranone to
methyl vinyl ketone for the construction of a chiral quaternary carbon center.
PMID- 25847448
TI - IL-1beta inhibits ILC3 while favoring NK-cell maturation of umbilical cord blood
CD34(+) precursors.
AB - NK cells are innate lymphocytes characterized by the expression of nuclear factor
interleukin 3 regulated (NFIL3 or E4BP4), eomesodermin (EOMES) transcription
factors (TFs), and by the ability to exert cytolytic activity and release IFN
gamma. In the haploidentical-hematopoietic stem cell transplantation (haplo-HSCT)
setting, CD34(+) donor derived NK cells play a major role in the control of
leukemic relapses. Therefore, it is important to better define cytokines that
influence NK-cell differentiation from CD34(+) precursors. We analyzed the
effects of IL-1beta on NK-cell differentiation from umbilical cord blood (UCB)
CD34(+) cells. While IL-1beta inhibited CD161(+) CD56(+) cell proliferation, an
increased expression of LFA-1, CD94/NKG2A, KIRs, and perforin on CD56(+) cells
was detected. In addition, within the CD161(+) CD56(+) IL-1RI(+) LFA-1(-) cell
fraction (representing group 3 innate lymphoid cells, ILC3-like cells), a
significant increase of EOMES, NKp46, and CD94/NKG2A receptors, cytolytic
granules, and IFN-gamma was detected. This increase was paralleled by a decrease
of related orphan receptors (RORgammat) TF, NKp44 expression, and IL-22
production. These data suggest that IL-1beta inhibits ILC3- while favoring NK
cell maturation. Since in haplo-HSCT conditioning regimen, infections or residual
leukemia cells may induce IL-1beta production, this may influence the NK/ILC3
development from donor-derived CD34(+) precursors.
PMID- 25847450
TI - Immune responses of wild birds to emerging infectious diseases.
AB - Over the past several decades, outbreaks of emerging infectious diseases (EIDs)
in wild birds have attracted worldwide media attention, either because of their
extreme virulence or because of alarming spillovers into agricultural animals or
humans. The pathogens involved have been found to infect a variety of bird hosts
ranging from relatively few species (e.g. Trichomonas gallinae) to hundreds of
species (e.g. West Nile Virus). Here we review and contrast the immune responses
that wild birds are able to mount against these novel pathogens. We discuss the
extent to which these responses are associated with reduced clinical symptoms,
pathogen load and mortality, or conversely, how they can be linked to worsened
pathology and reduced survival. We then investigate how immune responses to EIDs
can evolve over time in response to pathogen-driven selection using the
illustrative case study of the epizootic outbreak of Mycoplasma gallisepticum in
wild North American house finches (Haemorhous mexicanus). We highlight the need
for future work to take advantage of the substantial inter- and intraspecific
variation in disease progression and outcome following infections with EID to
elucidate the extent to which immune responses confer increased resistance
through pathogen clearance or may instead heighten pathogenesis.
PMID- 25847449
TI - Combination of 12-O-tetradecanoylphorbol-13-acetate with diethyldithiocarbamate
markedly inhibits pancreatic cancer cell growth in 3D culture and in
immunodeficient mice.
AB - The aim of the present study was to determine the effects of 12-O
tetradecanoylphorbol-13-acetate (TPA) and diethyldithiocarbamate (DDTC) alone or
in combination on human pancreatic cancer cells cultured in vitro and grown as
xenograft tumors in nude mice. Pancreatic cancer cells were treated with either
DDTC or TPA alone, or in combination and the number of viable cells was then
determined by trypan blue ecxlusion assay and the number of apoptotic cells was
determined by morphological assessment by staining the cells with propidium
idiode and examining them under a fluorescence microscope. Treatment with DDTC or
TPA alone inhibited the growth and promoted the apoptosis of pancreatic cancer
cells in a concentration-dependent manner. These effects were more prominent
following treatment with TPA in combination with DDTC than following treatment
with either agent alone in PANC-1 cells in monolayer cultures and in 3
dimensional (3D) cultures. The potent effects of the combination treatment on
PANC-1 cells were associated with the inhibition of nuclear factor-kappaB (NF
kappaB) activation and the decreased expression of Bcl-2 induced by DDTC, as
shown by NF-kappaB-dependent reporter gene expression assay and western blot
analysis. Furthermore, treatment of nude mice with DDTC + TPA strongly inhibited
the growth of PANC-1 xenograft tumors. The results of the present study indicate
that the administration of TPA and DDTC in combination may be an effective
strategy for inhibiting the growth of pancreatic cancer.
PMID- 25847451
TI - Comparison of mouse plasma and brain tissue homogenate sample pretreatment
methods prior to high-performance liquid chromatography for a new 1,2,4-triazole
derivative with anticonvulsant activity.
AB - The focus of the study was to develop a bio-analytical assay for a 1,2,4-triazole
derivative from plasma and brain tissue homogenate samples. The goal was to
compare analytical techniques that facilitate high accuracy with simplified
sample processing. In this study, commonly used standard protein precipitation
and solid-phase extraction methods utilizing C18 and cartridges of Hybrid
technology were compared in terms of their ability for sample pretreatment and
removal of biological matrices before high-performance liquid chromatography
quantification. Fast classical reversed-phase chromatography on a C18 column
paired with selective sample preparation using Hybrid solid-phase extraction
technology resulted in the most precise bio-analytical determination of the
hydrophobic 1,2,4-triazole derivative in both biological samples studied. The
obtained recovery values were above 95% with the coefficient of variation lower
than 5%.
PMID- 25847452
TI - Is drug-eluting-bead transcatheter arterial chemoembolization (TACE) associated
with better tumor response than conventional TACE in a meta-analysis?: Authors'
reply.
PMID- 25847453
TI - Undecametallic and hexadecametallic ferric oxo-hydroxo/ethoxo pivalate clusters.
AB - Synthesis strategies for highly condensed {Fe11} and {Fe16} pivalate clusters
have been developed based on archetypal geometrically frustrated triangular
{Fe3(MU3-O)} motifs that are interlinked via oxo, hydroxo, ethoxo, and
carboxylate groups.
PMID- 25847454
TI - Reticulate evolution and sea-level fluctuations together drove species
diversification of slipper orchids (Paphiopedilum) in South-East Asia.
AB - South-East Asia covers four of the world's biodiversity hotspots, showing high
species diversity and endemism. Owing to the successive expansion and contraction
of distribution and the fragmentation by geographical barriers, the tropical
flora greatly diversified in this region during the Tertiary, but the
evolutionary tempo and mode of species diversity remain poorly investigated.
Paphiopedilum, the largest genus of slipper orchids comprising nearly 100
species, is mainly distributed in South-East Asia, providing an ideal system for
exploring how plant species diversity was shaped in this region. Here, we
investigated the evolutionary history of this genus with eight cpDNA regions and
four low-copy nuclear genes. Discordance between gene trees and network analysis
indicates that reticulate evolution occurred in the genus. Ancestral area
reconstruction suggests that vicariance and long-distance dispersal together led
to its current distribution. Diversification rate variation was detected and
strongly correlated with the species diversity in subg. Paphiopedilum (~80
species). The shift of speciation rate in subg. Paphiopedilum was coincident with
sea-level fluctuations in the late Cenozoic, which could have provided ecological
opportunities for speciation and created bridges or barriers for gene flow.
Moreover, some other factors (e.g. sympatric distribution, incomplete
reproductive barriers and clonal propagation) might also be advantageous for the
formation and reproduction of hybrid species. In conclusion, our study suggests
that the interplay of reticulate evolution and sea-level fluctuations has
promoted the diversification of the genus Paphiopedilum and sheds light into the
evolution of Orchidaceae and the historical processes of plant species
diversification in South-East Asia.
PMID- 25847455
TI - Permeability and shear modulus of articular cartilage in growing mice.
AB - Articular cartilage maturation is the postnatal development process that adapts
joint surfaces to their site-specific biomechanical demands. Understanding the
changes in mechanical tissues properties during growth is a critical step in
advancing strategies for orthopedics and for cell- and biomaterial- based
therapies dedicated to cartilage repair. We hypothesize that at the microscale,
the articular cartilage tissue properties of the mouse (i.e., shear modulus and
permeability) change with the growth and are dependent on location within the
joint. We tested cartilage on the medial femoral condyle and lateral femoral
condyle of seven C57Bl6 mice at different ages (2, 3, 5, 7, 9, 12, and 17 weeks
old) using a micro-indentation test. Results indicated that permeability
decreased with age from 2 to 17 weeks. Shear modulus reached a peak at the end of
the growth (9 weeks). Within an age group, shear modulus was higher in the MFC
than in the LFC, but permeability did not change. We have developed a method that
can measure natural alterations in cartilage material properties in a murine
joint, which will be useful in identifying changes in cartilage mechanics with
degeneration, pathology, or treatment.
PMID- 25847456
TI - Fabrication of drug-loaded anti-infective guided tissue regeneration membrane
with adjustable biodegradation property.
AB - For guided tissue regeneration (GTR) membrane, synchronization of the membrane
biodegradation rate and tissue regeneration rate is important. Besides, the major
reason for GTR membrane failure in clinical application is infection which can be
prevented by loading anti-bacterial drug. To realize the consistency in membrane
degradation rate and tissue regeneration rate of the anti-infective membrane, we
developed metronidazole-loaded electrospun poly(E-caprolactone)-gelatin nanofiber
membranes with different poly(E-caprolactone)/gelatin ratios (95:5, 90:10, 80:20,
70:30, 60:40, and 50:50). Homogeneous nanofibers were successfully fabricated.
The mechanical strength of the membranes increased with the poly(E-caprolactone)
content, while the hydrophilicity decreased. The controlled and sustained release
of metronidazole from all the membranes prevented the colonization of anaerobic
bacteria. At all poly(E-caprolactone)/gelatin ratios, all the membranes presented
good biocompatibility while the increase of gelatin content resulted in enhanced
cell adhesion and proliferation. Subcutaneous implantation in rabbits for 8
months demonstrated that all the membranes showed good biocompatibility without
infection. Both in vitro and in vivo results showed that the biodegradation rate
of the membranes was accelerated with the increase of gelatin content. The
biodegradation rate and biocompatibility of the membranes can be adjusted by
changing the PCL/gelatin ratio. The optimal membrane can be chosen based on the
patient and tissue type to realize the synchronization of membrane degradation
with tissue regeneration for the best treatment effect.
PMID- 25847457
TI - In vitro and in vivo toxicity evaluation of plant virus nanocarriers.
AB - The use of biological self-assembling materials, plant virus nanoparticles in
particular, appears very intriguing as it allows a great choice of symmetries and
dimensions, easy chemical and biological engineering of both surface and/or
internal cavity as well as safe and rapid production in plants. In this
perspective, we present an initial evaluation of the safety profile of two
structurally different plant viruses produced in Nicotiana benthamiana L. plants:
the filamentous Potato virus X and the icosahedral Tomato bushy stunt virus. In
vitro haemolysis assay was used to test the cytotoxic effects, which could arise
by pVNPs interaction with cellular membranes, while early embryo assay was used
to evaluate toxicity and teratogenicity in vivo. Data indicates that these
structurally robust particles, still able to infect plants after incubation in
serum up to 24h, have neither toxic nor teratogenic effects in vitro and in vivo.
This work represents the first safety-focused characterization of pVNPs in view
of their possible use as drug delivery carriers.
PMID- 25847458
TI - Layer by layer assembled films between hemoglobin and multiwall carbon nanotubes
for pH-switchable biosensing.
AB - Although pH-switchable behaviors have been reported based on multilayer films
modified electrodes, their pH-switchable biosensing is still difficult due to the
existence of the electroactive mediator. In this study, we report the pH
dependable determination of hydrogen peroxide (H2O2) based on a four-bilayer film
fabricated through layer by layer assembly between hemoglobin (Hb) and multiwall
carbon nanotubes (MWCNTs). We observed that response of electroactive probe
Fe(CN)6(3-) at the multilayer films was very sensitive and reversible to pH
values of phosphate buffer solutions phosphate buffer solution with cyclic
voltammetry. The reduction peak height of Fe(CN)6(3-) at the multilayer film
could reach ~221MUA at pH 3.0 while 0MUA at pH 9.0. The linear range for the
detection of H2O2 at pH 3.0 was from 12.5MUM to 10.4mM, which was much wider than
that at pH 9.0. Our results demonstrated that the detection of H2O2 with the
proposed modified electrode is dependent on pH values of phosphate buffer
solution. Moreover, the component of multilayer films has impacts on the
performance of biosensors with pH-switchable behaviors.
PMID- 25847459
TI - Nanostructured sensor based on carbon nanotubes and clavanin A for bacterial
detection.
AB - Unusual methods for specific detection of pathogenic bacteria are becoming key
points for control and identification of problems related to health and
(bio)safety. In this context, this work aims to propose a new approach for the
development of nanostructured biosensors based on carbon nanotubes (CNTs) and
antimicrobial peptides for bacterial detection. Firstly, the antimicrobial
peptide clavanin A (ClavA) was chemically immobilized on CNTs and surface
immobilized ClavA was used to detect Klebsiella pneumoniae, Enterococcus
faecalis, Escherichia coli and Bacillus subtilis in a direct assay format. We
used electrochemical impedance spectroscopy technique to evaluate the
effectiveness and sensitivity of the ClavA-based biosensors by measuring the
modifications in their electrochemical responses before and after incubation in
presence of different bacteria concentrations. The biosensor was able to
discriminate between bacteria concentrations in the 10(2)-10(6)CFU mL(-1) range.
Atomic force microscopy analysis confirmed the biosensor functionality for
bacterial recognition. This new sensor system was capable of differentiating
between Gram-positive and Gram-negative bacteria, since ClavA showed different
affinities toward the pathogenic bacteria species.
PMID- 25847460
TI - Why searching for psychosis in diverse settings is important for global research
and mental health systems development.
AB - BACKGROUND: The INTREPID programme of research aims to establish comparable
studies of incident psychosis in a number of low- and middle-income countries
(LMICs). DISCUSSION: The importance of this cannot be under-estimated, as this
will enable the testing of existing findings and evidence across differing
environmental contexts; and will permit the identification of new and unique
evidence that is only apparent within specific contexts. The epidemiological,
aetiological and phenomenological insights derived from this programme are likely
to inform major research advances of the next decades. Of equal importance, by
adopting novel methods for detecting psychosis 'cases' in low-resourced settings,
the researchers will be able to test two key hypotheses that could revolutionize
clinical research and service provision within LMIC settings: (1) that informal
providers can be incorporated successfully into an adequate (and perhaps even
superior) case-detection system that is community and population-based (rather
than hospital-based); and (2) that informal providers can be integrated
meaningfully into the pathway to care (and perhaps even long-term management) of
patients with incident psychosis living in low-resourced settings.
PMID- 25847461
TI - Belatacept in recurrent focal segmental glomerulosclerosis after kidney
transplantation.
PMID- 25847463
TI - Oral Mucoceles in Children--Analysis of 56 New Cases.
AB - BACKGROUND: Mucoceles are common cystic lesions of the oral mucosa. Extravasation
mucoceles (EMs) are mainly found in the lower lip of young patients, whereas
retention mucoceles (RMs) are usually located in the cheek or palate of older
patients. This study was undertaken to more fully characterize the
clinicopathologic features of mucoceles in pediatric patients. METHODS: The
records of 56 pediatric patients with mucoceles were included in the study. Age,
sex, history of trauma, intraoral site, size, and method of treatment were
evaluated. Histopathologically the lesions were classified as being EMs or RMs.
RESULTS: The age range was 1.5 to 16 years (mean age 11.2 yrs). Of the 56
patients, 24 (43%) were males and 32 (57%) were females, with a male:female ratio
of 1:1.33. A history of trauma was recorded in 32 (57%) patients of the lower
lip. The intraoral sites were the lower lip (38 [68%]), tongue (10 [18%]), and
floor of the mouth (8 [14%]). Of the 56 patients, 44 (79%) were EM and 12 (21%)
were ranulas. No RMs were found. Mucoceles ranged from 0.3 to 3.8 cm in diameter
(mean 0.9 cm). The treatment of EMs was surgical excision. Cryosurgey,
electrosurgery, and carbon dioxide laser were also used. CONCLUSION: In contrast
to adults, where EM and RM types can be found, among children all cases are of
the EM type. The disparate site and age incidences of EMs and RMs of the oral
mucosa suggest that these two types are not related and possibly have a different
etiopathogenesis.
PMID- 25847462
TI - Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare
condition caused by mutations in ASAH1.
AB - OBJECTIVE: To present the clinical features and the results of laboratory
investigations in three patients with spinal muscular atrophy associated with
progressive myoclonic epilepsy (SMA-PME), a rare condition caused by mutations in
the N-acylsphingosine amidohydrosilase 1 (ASAH1) gene. METHODS: The patients were
submitted to clinical evaluation, neurophysiologic investigations (that included
wakefulness and sleep electroencephalography [EEG], video-polygraphic recording
with jerk-locked back-averaging, multimodal evoked potentials, and
electromyography), brain magnetic resonance imaging (MRI), biochemical screening,
muscle and skin biopsies, and molecular genetic analysis. RESULTS: The main
clinical features were onset in childhood with proximal muscular weakness,
generalized epilepsy with absences and myoclonic seizures, cognitive impairment
of variable degree; the course was progressive with muscle wasting and
uncontrolled epileptic seizures. In one patient, earlier onset before the age of
2 years was associated with a more complex clinical picture, with abnormal eye
movements, progressive cognitive impairment, and a more rapid and severe course.
EEG/polygraphic data were consistent with PME, demonstrating generalized spike
and-wave discharges, evidence of positive and negative myoclonia, and prominent
photosensitivity. In one patient, transcranial magnetic stimulation showed a
hyperexcitable motor cortex, whereas somatosensory evoked potentials were
unaffected. Possible involvement of the central acoustic and visual pathways was
suggested by abnormal auditory and visual evoked potentials. Muscle biopsies
showed typical signs of neurogenic damage. Molecular genetic analysis showed
mutations of the ASAH1 gene. SIGNIFICANCE: Our data indicate that SMA-PME
associated with ASAH1 mutations is a genetically distinct condition with specific
clinical and neurophysiologic features. Further studies are warranted to explore
the role of the ASAH1 gene in muscle and brain function.
PMID- 25847464
TI - Biogeographic consequences of nutrient enrichment for plant-herbivore
interactions in coastal wetlands.
AB - A major challenge in ecology is to understand broadscale trends in the impact of
environmental change. We provide the first integrative analysis of the effects of
eutrophication on plants, herbivores, and their interactions in coastal wetlands
across latitudes. We show that fertilisation strongly increases herbivory in salt
marshes, but not in mangroves, and that this effect increases with increasing
latitude in salt marshes. We further show that stronger nutrient effects on plant
nitrogen concentration at higher latitudes is the mechanism likely underlying
this pattern. This biogeographic variation in nutrient effects on plant-herbivore
interactions has consequences for vegetation, with those at higher latitudes
being more vulnerable to consumer pressure fuelled by eutrophication. Our work
provides a novel, mechanistic understanding of how eutrophication affects plant
herbivore systems predictably across broad latitudinal gradients, and highlights
the power of incorporating biogeography into understanding large-scale
variability in the impacts of environmental change.
PMID- 25847465
TI - Prevalence, demographics, and complications of cleft palate surgery.
AB - INTRODUCTION: Current published data on the demographics of cleft lip and palate
is sparse and differs intranationally in reported incidence, demographics, and
complication rates, making accurate local data both valuable and useful. We
investigate the prevalence, demographics, and complications of cleft palate
correction surgery in the inpatient setting over a 15-year period. METHODS: A
retrospective review of The California Hospital Discharge Data sets of all
pediatric patients who underwent cleft palate repair or cleft palate revision
from 1997 to 2011. Children's hospitals (CHs) were analyzed as a separate group.
For each record, age, gender, ethnicity, length of stay, total charges, principal
payer, complications, and disposition were analyzed. RESULTS: 10,450 correction
surgeries were performed during 1997-2011. This was an annual case-volume of 697
and annual population-adjusted rate of 2.0, neither of which changed over time
(p=0.9 and 0.06, respectively). Of all surgeries, 21.5% were revisions, 48.3%
were performed in CHs, 56.2% were performed on males, and 65.5% were performed on
Caucasians. The median length of stay was 1 day, which did not change over time
(p=1.0). The median total charges increased from $9.074 to $35,643 over the
studied period (p<0.001). Admission to CHs was associated with shorter stay (1-3
days vs. 1-4 days) and higher total charges ($15,560 vs. $13,242; both p<0.001).
Complications occurred in 393 (3.8%) of the surgeries. This percentage did not
change over time (p=0.2). The most common complication was
fistula/abscess/infection, which occurred in 159 cases (1.5%). Respiratory
complications requiring ventilation occurred 66 cases (0.6%). Complications were
more common in CHs (4.8% vs. 2.8%; p<0.001). Mortality rate was <0.1%.
CONCLUSIONS: Our study constitutes the entire surgical cohort within a state,
allowing for an accurate representation of the true perioperative complication
rate of these procedures. The prevalence, demographics, and outcomes of the cleft
palate correction surgery have remained unchanged during 1997-2011. Collectively,
our data suggest that primary and secondary palatoplasty present low
perioperative risk.
PMID- 25847466
TI - May chronic rhinosinusitis in children be diagnosed by clinical symptoms?
AB - OBJECTIVES: Chronic rhinosinusitis (CRS) is a common disease in childhood but is
often underdiagnosed because the symptoms are subtle and similar to other nasal
pathologies. No clinical symptom is pathognomonic, and consensus documents
suggest nasal fibroendoscopy (NF) or imaging criteria (computed tomography,
magnetic resonance imaging) as the gold standards for diagnosis of CRS. However,
considering the frequent unavailability of such tools to physicians, we designed
this study to evaluate whether combinations of symptoms may achieve a clinical
diagnosis of CRS in children as confirmed by NF. METHODS: The study population
consisted of 275 children with a clinical diagnosis of CRS, in 228 of whom
diagnosis of CRS was confirmed by NF, while in 47 diagnosis was not confirmed by
NF and they served as the control group. The symptoms considered were nasal
obstruction, nasal discharge, cough, facial pain, and halitosis, using for
statistical analysis multivariate logistic regression, Wald tests, and receiver
operating characteristic (ROC) curve. RESULTS: The multivariate logistic
regression for CRS symptoms indicated rhinorrea as the strongest predictor of
CRS. With three symptoms the probability of CRS was from 60% to 75% without
rhinorrea and 77-91% in the presence of this symptom, with four symptoms the
probability was over 93%, and with all the five symptoms the probability of
having CRS was virtually 100%. CONCLUSIONS: These findings suggest that an
initial symptoms assessment may help to recognize children with a high
probability of CRS, thus reducing the need of NF or imaging techniques.
PMID- 25847467
TI - Antiviral treatment discontinuation among hepatitis C-infected individuals with
thrombocytopenia.
PMID- 25847468
TI - Misdiagnosis of patients may be derived from the interfering factors and used cut
offs in indexes.
PMID- 25847469
TI - Answer to 'Misdiagnosis of patients may be derived from the interfering factors
and used cut-offs in indexes'.
PMID- 25847471
TI - Theodore Lionel Sourkes obituary.
PMID- 25847470
TI - Synthetic Active Site Model of the [NiFeSe] Hydrogenase.
AB - A dinuclear synthetic model of the [NiFeSe] hydrogenase active site and a
structural, spectroscopic and electrochemical analysis of this complex is
reported. [NiFe('S2Se2')(CO)3] (H2'S2Se2' = 1,2-bis(2-thiabutyl-3,3-dimethyl-4
selenol)benzene) has been synthesized by reacting the nickel selenolate complex
[Ni('S2Se2')] with [Fe(CO)3bda] (bda = benzylideneacetone). X-ray crystal
structure analysis confirms that [NiFe('S2Se2')(CO)3] mimics the key structural
features of the enzyme active site, including a doubly bridged heterobimetallic
nickel and iron center with a selenolate terminally coordinated to the nickel
center. Comparison of [NiFe('S2Se2')(CO)3] with the previously reported thiolate
analogue [NiFe('S4')(CO)3] (H2'S4' = H2xbsms = 1,2-bis(4-mercapto-3,3-dimethyl-2
thiabutyl)benzene) showed that the selenolate groups in [NiFe('S2Se2')(CO)3] give
lower carbonyl stretching frequencies in the IR spectrum. Electrochemical studies
of [NiFe('S2Se2')(CO)3] and [NiFe('S4')(CO)3] demonstrated that both complexes do
not operate as homogenous H2 evolution catalysts, but are precursors to a solid
deposit on an electrode surface for H2 evolution catalysis in organic and aqueous
solution.
PMID- 25847472
TI - Development and validation of a clinical scale for rating the severity of
blepharospasm.
AB - Existing scales for rating the severity of blepharospasm (BSP) are limited by a
number of potential drawbacks. We therefore developed and validated a novel scale
for rating the severity of BSP. The development of the scale started with careful
examination of the clinical spectrum of the condition by a panel of experts who
selected phenomenological aspects thought to be relevant to disease severity.
Thereafter, selected items were first checked for reliability, then reliable
items were combined to generate the scale, and clinimetric properties of the
scale were evaluated. Finally, the confidence with which the scale could be used
by people without high levels of movement disorders skill was assessed. The new
scale, based on objective criteria, yielded moderate to almost perfect
reliability, acceptable internal consistency, satisfactory scaling assumptions,
lack of floor and ceiling effects, partial correlations with a prior severity
scale and with a quality of life scale, and good sensitivity to change. Despite a
few limitations, the foregoing features make the novel scale more suitable than
existing scales to assess the severity of BSP in natural history and
pathophysiologic studies as well as in clinical trials.
PMID- 25847473
TI - Anti-influenza virus effects of cocoa.
AB - BACKGROUND: Cocoa contains biologically active ingredients that have broad
spectrum antimicrobial activity, which includes an inhibitory effect on influenza
virus infection. RESULTS: A cocoa extract (CE) was prepared by treating defatted
cocoa powder with boiling water. The extract demonstrated dose-dependent
inhibition of infection in Madin-Darby canine kidney (MDCK) cells infected with
human influenza virus A (H1N1, H3N2), human influenza virus B and avian influenza
viruses (H5N1, H5N9). CE inhibited viral adsorption to MDCK cells. Animal
experiments showed that CE significantly improved survival in mice after intra
nasal administration of a lethal dose of influenza virus. In human intervention
trials, participants were allocated to two groups, one in which the participants
ingested cocoa for 3 weeks before and after vaccination against A(H1N1)pdm2009
influenza virus and another in which the participants did not ingest cocoa.
Neutralizing antibody titers against A(H1N1)pdm2009 influenza virus increased
significantly in both groups; however, the extent of the increase was not
significantly different between the two groups. Although natural killer cell
activity was also elevated in both groups, the increase was more substantial in
the cocoa intake group. CONCLUSION: Drinking cocoa activates natural immunity and
enhances vaccination-induced immune response, providing stronger protection
against influenza virus infection and disease onset.
PMID- 25847474
TI - Higher incidence of esophageal lesions after ablation of atrial fibrillation
related to the use of esophageal temperature probes.
AB - BACKGROUND: Endoscopically detected esophageal lesions (EDELs) have been
identified in apparently asymptomatic patients after catheter ablation of atrial
fibrillation (AF). The use of esophageal probes to monitor luminal esophageal
temperature (LET) during catheter ablation to protect esophageal damage is
currently controversial. OBJECTIVE: The purpose of this study was to investigate
the impact of the use of esophageal temperature probes during AF catheter
ablation on the incidence of EDELs. METHODS: Eighty consecutive patients (mean
age 63.8 +/- 11.36 years; 68.8% men) with symptomatic, drug-refractory paroxysmal
(n = 52, 65%) or persistent AF who underwent left atrial radiofrequency catheter
ablation were prospectively enrolled. Posterior wall ablation was power limited
(<=25 W). In the first 40 patients, LET was monitored continuously (group A),
whereas no esophageal temperature probe was used in group B (n = 40 patients).
Assessment of EDEL was performed by endoscopy within 2 days after radiofrequency
catheter ablation. RESULTS: Overall, 13 patients (16%) developed EDELs after AF
ablation. The incidence of EDELs was significantly higher in group A than group B
(30% vs 2.5%, P < .01). Within group A, patients who developed EDEL had higher
maximal LET during AF ablation than patients without EDEL (40.97 +/- 0.92 degrees
C vs 40.14 +/- 1.1 degrees C, P = .02). Multivariable logistic regression
analysis revealed the use of an esophageal temperature probe as the only
independent predictor for the development of EDEL (odds ratio 16.7, P < .01).
CONCLUSION: The use of esophageal temperature probes in the setting of AF
catheter ablation per se appears to be a risk factor for the development of EDEL.
PMID- 25847476
TI - Differentiating the origin of outflow tract ventricular arrhythmia using a
simple, novel approach.
AB - BACKGROUND: Numerous electrocardiographic (ECG) criteria have been proposed to
identify localization of outflow tract ventricular arrhythmias (OT-VAs); however,
in some cases, it is difficult to accurately localize the origin of OT-VA using
the surface ECG. OBJECTIVE: The purpose of this study was to assess a simple
criterion for localization of OT-VAs during electrophysiology study. METHODS: We
measured the interval from the onset of the earliest QRS complex of premature
ventricular contractions (PVCs) to the distal right ventricular apical signal
(the QRS-RVA interval) in 66 patients (31 men aged 53.3 +/- 14.0 years; right
ventricular outflow tract [RVOT] origin in 37) referred for ablation of
symptomatic outflow tract PVCs. We prospectively validated this criterion in 39
patients (22 men aged 52 +/- 15 years; RVOT origin in 19). RESULTS: Compared with
patients with RVOT PVCs, the QRS-RVA interval was significantly longer in
patients with left ventricular outflow tract (LVOT) PVCs (70 +/- 14 vs 33.4+/-10
ms, P < .001). Receiver operating characteristic analysis showed that a QRS-RVA
interval >=49 ms had sensitivity, specificity, and positive and negative
predictive values of 100%, 94.6%, 93.5%, and 100%, respectively, for prediction
of an LVOT origin. The same analysis in the validation cohort showed sensitivity,
specificity, and positive and negative predictive values of 94.7%, 95%, 95%, and
94.7%, respectively. When these data were combined, a QRS-RVA interval >=49 ms
had sensitivity, specificity, and positive and negative predictive values of 98%,
94.6%, 94.1%, and 98.1%, respectively, for prediction of an LVOT origin.
CONCLUSION: A QRS-RVA interval >=49 ms suggests an LVOT origin. The QRS-RVA
interval is a simple and accurate criterion for differentiating the origin of
outflow tract arrhythmia during electrophysiology study; however, the accuracy of
this criterion in identifying OT-VA from the right coronary cusp is limited.
PMID- 25847475
TI - Complications from prophylactic replacement of cardiac implantable electronic
device generators in response to United States Food and Drug Administration
recall: A systematic review and meta-analysis.
AB - BACKGROUND: The number of cardiac implantable electronic device (CIED) recalls
and advisories has increased over the past 3 decades, yet no consensus exists on
how to best manage patients with these CIEDs, partially because rates of
complications from prophylactic replacement are unknown. OBJECTIVE: The purpose
of this study was to establish rates of complications when recalled CIED
generators are replaced prophylactically. METHODS: We searched MEDLINE and the
Cochrane Controlled Trials Register for reports of prophylactic replacement of
recalled CIED generators. Studies with <20 subjects were excluded. We then
conducted a meta-analysis of qualifying studies to determine the rates of
combined major complications, mortality, and reoperation. RESULTS: We identified
7 citations that met our inclusion criteria and reported >=1 end-points of
interest. Four were single center, and 3 were multicenter. Six studies collected
data retrospectively (n = 1213) and 1 prospectively (n = 222). Using a random
effects model to combine data from all included studies, the rate of major
complications was 2.5% (95% confidence interval [CI] 1.0%-4.5%). Combining data
from 6 studies reporting mortality and reoperation, the rates were 0.5% (95% CI
0.1%-0.9%) and 2.5% (95% CI 0.8%-4.5%), respectively. CONCLUSION: Prophylactic
replacement of recalled CIED generators is associated with a low mortality rate
but nontrivial rates of other major complications similar to those reported when
CIED generators are replaced for other reasons. Thus, when considering replacing
a recalled CIED generator, known risks of elective generator replacement likely
apply and can be weighed against risks associated with device failure.
PMID- 25847477
TI - Incidence and characteristics of complications in the setting of second
generation cryoballoon ablation: A large single-center study of 500 consecutive
patients.
AB - BACKGROUND: The second-generation cryoballoon Advance (CB-A) recently launched on
the market has technical modifications designed to significantly improve
procedural outcome with respect to the first-generation device. OBJECTIVE: The
purpose of this study was to evaluate the overall incidence of complications in a
large sample of patients having undergone pulmonary vein (PV) isolation with CB-A
technology. METHODS: All consecutive patients who underwent PV isolation
procedures using CB-A technology between June 2012 and February 2015 were
considered. Exclusion criteria were presence of an intracavitary thrombus,
uncontrolled heart failure, moderate or severe valvular disease, left atrial
diameter >=55 mm, and contraindications to general anesthesia. RESULTS: During
the study period, 500 consecutive patients (67% male, age 57.6 +/- 12.9 years)
were enrolled. Major complications occurred in 10 patients (2.0%): vascular
complications at the puncture site in 6 (1.2%), and thromboembolic events,
cardiac tamponade, persisting phrenic nerve palsy, and retroperitoneal hematoma
all occurred in a single patient respectively (0.2%). Phrenic nerve palsy
occurred in 36 patients (7.2%) and did not revert in only 1 patient at final
follow-up of 20 months. No deaths related to the procedure occurred. No
predictors of major complication were found. CONCLUSION: The present findings
highlight that PV isolation using CB-A technology can be safely performed with a
low incidence of adverse events. The incidence of major complications after
atrial fibrillation ablation procedures using CB-A technology was 2% in our
study. The most frequent complication consisted of vascular complications at the
puncture site. No deaths related to the procedure occurred.
PMID- 25847478
TI - Amino-terminal B-natriuretic peptide levels and postablation recurrence in
hypertensive patients with paroxysmal atrial fibrillation.
AB - BACKGROUND: Amino-terminal B-type natriuretic peptide (NT-proBNP) has been shown
to predict postablation recurrences of atrial fibrillation (AF); however, given
the associations of natriuretic peptides with various cardiovascular parameters
potentially related to AF, whether the observed association with recurrence is
truly an independent one is not clear. OBJECTIVE: The purpose of this analysis
was to assess the association of NT-proBNP levels with AF recurrence after
radiofrequency ablation. METHODS: This was a post hoc analysis of a prospective
study of 296 hypertensive patients with symptomatic paroxysmal AF and no history
of heart failure who were scheduled to undergo pulmonary vein isolation. NT
proBNP was measured at baseline, and patients were followed for a median of 13.7
months. RESULTS: NT-proBNP levels at baseline were higher in patients with
recurrence (269 pg/mL [199-361 pg/mL]) vs those who remained arrhythmia-free (188
pg/mL [146-320 pg/mL], P<.001). In a univariate Cox regression model, each higher
quartile of NT-proBNP corresponded to a 47% (95% confidence interval 21.5%-77.9%)
increase in the risk of recurrence. However, when baseline clinical AF burden, in
terms of the number of clinical AF episodes in the previous year, was added to
the model, the association of NT-proBNP lost its significance (adjusted hazard
ratio 1.22, 95% confidence interval 0.94-1.57). CONCLUSION: This is the largest
series to date showing that NT-proBNP is a univariate predictor of postablation
AF recurrence. However, it seems that adjustment for other covariates, including
the number of AF episodes within the previous year, renders this association
nonsignificant.
PMID- 25847480
TI - A phase I study of resminostat in Japanese patients with advanced solid tumors.
AB - PURPOSE: This study was performed to evaluate the safety and determine the
recommended dose (RD) of resminostat monotherapy, an oral histone deacetylase
(HDAC) inhibitor, in Japanese patients with advanced solid tumors. METHODS:
Resminostat was administered to patients with advanced solid tumors on a 14-day
cycle consisting of once-daily administration on days 1-5. The dose was initiated
at 400 mg and increased to 600 mg and then 800 mg. Treatment with resminostat was
continued until disease progression or discontinuation for any other reason. Dose
limiting toxicities (DLTs) were assessed according to the adverse drug reactions
occurring in the first cycle. Secondary objectives included the pharmacokinetics,
pharmacodynamics, and efficacy. RESULTS: A total of 12 patients were enrolled in
the study and received resminostat. No DLTs were reported in any patient. The
maximum tolerated dose was not reached. Frequently reported grade 3/4 adverse
drug reactions were as follows: lymphocytopenia (33.3 %), thrombocytopenia (25.0
%), neutropenia (16.7 %), and leukocytopenia (16.7 %). Pharmacokinetic analysis
revealed that there was no accumulation of the drug over the 5-day administration
period and no significant difference in pharmacokinetic parameters between the
single dose and multiple doses. Measurement of acetylated H4 histone protein
levels in peripheral blood mononuclear cells demonstrated that resminostat
inhibited HDAC activity at all the doses assessed. No patients had a complete or
partial response, whereas three patients had stable disease. CONCLUSIONS:
Resminostat was safely administered to Japanese patients with advanced solid
tumors. The RD of resminostat monotherapy in Japanese patients was estimated to
be 800 mg.
PMID- 25847479
TI - Determinants of the activities of antifolates delivered into cells by folate
receptor-mediated endocytosis.
AB - PURPOSE: Elements in the endocytic process that are determinants of the
activities of antifolates delivered by folate-receptor alpha (FRalpha) were
explored. METHODS: Antifolate growth inhibition was assessed with a 1- or 5-day
exposure in reduced folate carrier-null HeLa cell lines that express a high level
of FRalpha in the presence or absence of the proton-coupled folate transporter
(PCFT). pH-dependent rates of dissociation from FRalpha were also determined.
RESULTS: With a 1-day drug exposure which is relevant to the pulse clinical
administration of these drugs, FRalpha expression enhanced raltitrexed activity
and modestly enhanced ZD9331 activity, but did not significantly augment the
activity of pemetrexed or lomotrexol. With a 5-day drug exposure, FRalpha
mediated growth inhibition was increased for raltitrexed and ZD9331 and emerged
for lomotrexol. While the FRalpha-augmented activity of lomotrexol and
raltitrexed did not require PCFT, augmentation of ZD9331 activity required the co
expression of PCFT with both 1- and 5-day exposures. In contrast, there was no
augmentation of pemetrexed activity by FRalpha under any condition. The
activities of these agents correlated with their rate of dissociation from the
receptor at acidic pH: raltitrexed > ZD9331 > lomotrexol > pemetrexed consistent
with insufficient pemetrexed release from FRalpha for export from the endosomes.
CONCLUSIONS: FRalpha is unlikely to contribute to the pharmacological activity of
antifolates, such as pemetrexed, that bind tightly to, and dissociate slowly
from, the receptor particularly when the exposure time is brief. While PCFT was
required for FRalpha-mediated ZD9931 activity, the activities of the other
antifolates was independent of PCFT.
PMID- 25847482
TI - Association between electrocardiographic findings, right heart strain, and short
term adverse clinical events in patients with acute pulmonary embolism.
AB - BACKGROUND: Electrocardiographic (ECG) changes may be seen with pulmonary emboli
(PE). Whether ECG is associated with short-term adverse clinical events after PE
is less well established. HYPOTHESIS: ECG findings are associated with short-term
clinical deterioration after PE. METHODS: Consecutive adult PE patients were
enrolled in an academic emergency department from 2008 to 2011. The primary
outcome was right heart strain (RHS) on echocardiogram or CT pulmonary
angiography, or TnT >=0.1 ng/mL. We derived an ECG (TwiST) score that is
associated with RHS and short-term adverse clinical events. RESULTS: We enrolled
298 patients with PE. On multivariate analysis, T-wave inversion in leads V(1)
through V(3) (OR: 4.7, 95% confidence interval [CI]: 1.7-13.2), S wave in lead I
(OR: 2.0, 95% CI: 1.1-3.5), and tachycardia (OR: 2.5, 95% CI: 1.3-4.8) were
associated with RHS. A TwiST score <=2 (n = 210, 72%) was 84% (95% CI: 77%-90%)
sensitive for the absence of RHS, whereas a TwiST score >=5 (n = 47, 16%) was 93%
(95% CI: 88%-97%) specific for the presence of RHS. CONCLUSIONS: A simple ECG
(TwiST) score can identify patients likely or not likely to have RHS with >80%
specificity and sensitivity and may assist in identifying patients with acute PE
at risk for adverse clinical events before pursuing other advanced imaging tests.
PMID- 25847481
TI - Clinical and molecular delineation of Tetrasomy 9p syndrome: report of 12 new
cases and literature review.
AB - Tetrasomy 9p is a generic term describing the presence of a supernumerary
chromosome incorporating two copies of the 9p arm. Two varieties exist:
isodicentric chromosome 9p (i(9p)), where the two 9p arms are linked by a single
centromeric region, and pseudodicentric 9p (idic(9p)), where one active and one
inactive centromere are linked together by a proximal segment of 9q that may
incorporate euchromatic material. In living patients, i(9p) and idic(9p) are
usually present in a mosaic state. Fifty-four cases, including fetuses, have been
reported, of which only two have been molecularly characterized using array-CGH.
Tetrasomy 9p leads to a variable phenotype ranging from multiple congenital
anomalies with severe intellectual disability and growth delay to subnormal
cognitive and physical developments. Hypertelorism, abnormal ears,
microretrognathia and bulbous nose are the most common dysmorphic traits.
Microcephaly, growth retardation, joint dislocation, scoliosis, cardiac and renal
anomalies were reported in several cases. Those physical anomalies are often, but
not universally, accompanied by intellectual disability. The most recurrent
breakpoints, defined by conventional cytogenetics, are 9p10, 9q12 and 9q13. We
report on 12 new patients with tetrasomy 9p (3 i(9p), 8 idic(9p) and one
structurally uncharacterized), including the first case of parental germline
mosaicism. All rearrangements have been characterized by DNA microarray. Based on
our results and a review of the literature, we further delineate the prenatal and
postnatal clinical spectrum of this imbalance. Our results show poor genotype
phenotype correlations and underline the need of precise molecular
characterization of the supernumerary marker.
PMID- 25847483
TI - F4+ enterotoxigenic Escherichia coli (ETEC) adhesion mediated by the major
fimbrial subunit FaeG.
AB - The FaeG subunit is the major constituent of F4(+) fimbriae, associated with
glycoprotein and/or glycolipid receptor recognition and majorly contributes to
the pathogen attachment to the host cells. To investigate the key factor involved
in the fimbrial binding of F4(+) Escherichia coli, both the recombinant E. coli
SE5000 strains carrying the fae operon gene clusters that express the different
types of fimbriae in vitro, named as rF4ab, rF4ac, and rF4ad, respectively,
corresponding to the fimbrial types F4ab, F4ac, and F4ad, and the three isogenic
in-frame faeG gene deletion mutants were constructed. The adhesion assays and
adhesion inhibition assays showed that DeltafaeG mutants had a significant
reduction in the binding to porcine brush border as well as the intestinal
epithelial cell lines, while the complemented strain DeltafaeG/pfaeG restored the
adhesion function. The recombinant bacterial strains rF4ab, rF4ac, and rF4ad have
the same binding property as wild-type F4(+) E. coli strains do and improvement
in terms of binding to porcine brush border and the intestinal epithelial cells,
and the adherence was blocked by the monoclonal antibody anti-F4 fimbriae. These
data demonstrate that the fimbrial binding of F4(+) E. coli is directly mediated
by the major FaeG subunit.
PMID- 25847485
TI - High sulfur content polymer nanoparticles obtained from interfacial
polymerization of sodium polysulfide and 1,2,3-trichloropropane in water.
AB - Sulfur-rich materials have recently attracted keen interest for their potentials
in optical, electrochemical, and pesticidal applications as well as their utility
in dynamic covalent bond chemistry. Many sulfur-rich polymers, however, are
insoluble and processing methods are therefore very limited. The synthesis and
characterization of water-dispersible polymer nanoparticles (NPs) with the sulfur
content exceeding 75% by weight, obtained from the interfacial polymerization
between 1,2,3-trichloropropane and sodium polysulfide in water is reported here.
The interfacial polymerization yields well-defined sulfur-rich NPs in the
presence of surfactants, which are capable of serving a dual role as a phase
transfer catalyst on top of emulsifiers. Such dual role allows for the control of
the product NP size by varying its concentration. The surfactants can be easily
removed by centrifugation and redispersion in water is also reported here. The
resulting sulfur-rich NPs are characterized through elemental analysis, dynamic
light scattering, zeta-potential measurements, and scanning electron microscopy.
PMID- 25847484
TI - The impact of neighborhood social and built environment factors across the cancer
continuum: Current research, methodological considerations, and future
directions.
AB - Neighborhood social and built environments have been recognized as important
contexts in which health is shaped. The authors reviewed the extent to which
these neighborhood factors have been addressed in population-level cancer
research by scanning the literature for research focused on specific social
and/or built environment characteristics and their association with outcomes
across the cancer continuum, including incidence, diagnosis, treatment,
survivorship, and survival. The commonalities and differences in methodologies
across studies, the current challenges in research methodology, and future
directions in this research also were addressed. The assessment of social and
built environment factors in relation to cancer is a relatively new field, with
82% of the 34 reviewed articles published since 2010. Across the wide range of
social and built environment exposures and cancer outcomes considered by the
studies, numerous associations were reported. However, the directions and
magnitudes of associations varied, in large part because of the variation in
cancer sites and outcomes studied, but also likely because of differences in
study populations, geographic regions, and, importantly, choice of neighborhood
measures and geographic scales. The authors recommend that future studies
consider the life-course implications of cancer incidence and survival, integrate
secondary and self-report data, consider work neighborhood environments, and
further develop analytical and statistical approaches appropriate to the
geospatial and multilevel nature of the data. Incorporating social and built
environment factors into research on cancer etiology and outcomes can provide
insights into disease processes, identify vulnerable populations, and generate
results with translational impact of relevance for interventionists and policy
makers.
PMID- 25847486
TI - Macroeconomics of Natural Disasters: Strengths and Weaknesses of Meta-Analysis
Versus Review of Literature.
AB - We use the case of the macroeconomic impact of natural disasters to analyze
strengths and weaknesses of meta-analysis in an emerging research field.
Macroeconomists have published on this issue since 2002 (we identified 60 studies
to date). The results of the studies are contradictory and therefore the need to
synthesize the available research is evident. Meta-analysis is a useful method in
this field. An important aim of our article is to show how one can use the
identified methodological characteristics to better understand the robustness and
importance of new findings. To provide a comparative perspective, we contrast our
meta-analysis and its findings with the major influential research synthesis in
the field: the IPCC's 2012 special report Managing the Risks of Extreme Events
and Disasters to Advance Climate Change Adaptation. We show that the IPCC could
have been more confident about the negative economic impact of disasters and more
transparent on inclusion and qualification of studies, if it had been
complemented by a meta-analysis. Our meta-analysis shows that, controlling for
modeling strategies and data set, the impact of disasters is significantly
negative. The evidence is strongest for direct costs studies where we see no
difference between our larger sample and the studies included in the IPCC report.
Direct cost studies and indirect cost studies differ significantly, both in terms
of the confidence that can be attached to a negative impact of natural disasters
and in terms of the sources of heterogeneity of the findings reported in the
primary studies.
PMID- 25847487
TI - Strontium-impregnated bioabsorbable composite for osteoporotic fracture fixation.
AB - Osteoporosis impairs the bone-healing process as well as bone fracture fixation.
The intervention of osteoporosis is considered to be one part of bone fracture
treatment. Thus, orthopedic fixators impregnated with antiosteoporosis regimens
will improve fracture fixation in osteoporotic bone. In this study, the strontium
(Sr) and calcium phosphate ceramic (CPC) were mixed first and then mixed with
poly(epsilon-caprolactone) (PCL) to fabricate a bioactive and bioabsorbable bone
fixators. The prepared Sr-CPC/PCL screws were implanted into the distal femur of
ovariectomized rabbits. The results showed that Sr-CPC/PCL composite had the
appropriate mechanical properties, good biocompatibility, and radio-opacity. The
Sr addition created a porous structure and accelerated the degradation of bone
screws, but the degradation products did not acidify the surrounding environment.
For osteoporotic animals, favorable osteointegration around the Sr-CPC/PCL screws
was found, and the total porosity of trabecular bone was decreased under the
inspections of micro-computerized tomography. Compared with PCL or CPC/PCL screw,
animals which received Sr-CPC/PCL were found to have better results in terms of
trabecular number, thickness, and separation. This study reveals that the Sr
impregnated bone fixator improves osseointegration in osteoporotic animals. Sr
CPC/PCL composite is a good candidate material for osteofixation in osteoporotic
patients.
PMID- 25847488
TI - Maternal vitamin D levels are inversely related to allergic sensitization and
atopic diseases in early childhood.
AB - BACKGROUND: There are few studies addressing the impact of maternal vitamin D
status on the vitamin D levels in offspring, their sensitization to common
allergens and atopic disease development. METHODS: Children aged 0 through 4 yr
from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH)
study were enrolled. Time series of serum 25-hydroxyvitamin D (25(OH)D) levels
were measured in maternal blood before delivery, cord blood, and at age 1.5, 3,
and 4 using an electrochemiluminescence-based assay. Specific IgE antibodies
against food and inhalant allergens were measured at 6 months, and 1, 1.5, 2, 3,
and 4 yr of age. RESULTS: A total of 164 mother-child pairs from a birth cohort
were recruited in this study. The mean levels of maternal 25(OH)D were 23.2 +/-
7.7 ng/ml with a high (up to 80%) prevalence of insufficient vitamin D status (<
30 ng/ml). A significant correlation was seen between maternal and cord blood
25(OH)D levels (p < 0.001), and a persistent lower 25(OH)D level was found in
children born to mothers with deficient 25(OH)D levels. Deficient maternal
25(OH)D levels (<20 ng/ml) appeared to be associated with a higher prevalence of
allergen sensitization before age 2. Higher maternal 25(OH)D levels were
significantly associated with lower risk of eczema (OR 0.12; 95% CI 0.02-0.63; p
= 0.012) and asthma (OR 0.22; 95% CI 0.06-0.92; p = 0.038) at age 4. CONCLUSIONS:
Low maternal 25(OH)D levels appear not only to be associated with an increase in
the prevalence of allergic sensitization but also the risk of eczema and asthma
in early childhood.
PMID- 25847490
TI - Characterization and evolutionary analysis of tributyltin-binding protein and
pufferfish saxitoxin and tetrodotoxin-binding protein genes in toxic and nontoxic
pufferfishes.
AB - Understanding the evolutionary mechanisms of toxin accumulation in pufferfishes
has been long-standing problem in toxicology and evolutionary biology. Pufferfish
saxitoxin and tetrodotoxin-binding protein (PSTBP) is involved in the transport
and accumulation of tetrodotoxin and is one of the most intriguing proteins
related to the toxicity of pufferfishes. PSTBPs are fusion proteins consisting of
two tandem repeated tributyltin-binding protein type 2 (TBT-bp2) domains. In this
study, we examined the evolutionary dynamics of TBT-bp2 and PSTBP genes to
understand the evolution of toxin accumulation in pufferfishes. Database searches
and/or PCR-based cDNA cloning in nine pufferfish species (6 toxic and 3 nontoxic)
revealed that all species possessed one or more TBT-bp2 genes, but PSTBP genes
were found only in 5 toxic species belonging to genus Takifugu. These toxic
Takifugu species possessed two or three copies of PSTBP genes. Phylogenetic
analysis of TBT-bp2 and PSTBP genes suggested that PSTBPs evolved in the common
ancestor of Takifugu species by repeated duplications and fusions of TBT-bp2
genes. In addition, a detailed comparison of Takifugu TBT-bp2 and PSTBP gene
sequences detected a signature of positive selection under the pressure of gene
conversion. The complicated evolutionary dynamics of TBT-bp2 and PSTBP genes may
reflect the diversity of toxicity in pufferfishes.
PMID- 25847489
TI - Sann-Joong-Kuey-Jian-Tang induces autophagy in HepG2 cells via regulation of the
phosphoinositide-3 kinase/Akt/mammalian target of rapamycin and p38 mitogen
activated protein kinase pathways.
AB - Sann-Joong-Kuey-Jian-Tang (SJKJT), a traditional Chinese medicine, was previously
reported to induce autophagy and inhibit the proliferation of the human HepG2
hepatocellular carcinoma cell line via an extrinsic pathway. In the present
study, the effects of SJKJT-induced autophagy and the cytotoxic mechanisms
mediating these effects were investigated in HepG2 cells. The cytotoxicity of
SJKJT in the HepG2 cells was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide assay. The results demonstrated that the half-maximal
inhibitory concentration of SJKJT was 2.91 mg/ml at 24 h, 1.64 mg/ml at 48 h and
1.26 mg/ml at 72 h. The results of confocal fluorescence microscopy indicated
that SJKJT resulted in the accumulation of green fluorescent protein-LC3 and
vacuolation of the cytoplasm. Flow cytometric analysis revealed the accumulation
of acidic vesicular organelles. Furthermore, western blot analysis, used to
determine the expression levels of autophagy-associated proteins, demonstrated
that the HepG2 cells treated with SJKJT exhibited LC3B-I/LC3B-II conversion,
increased expression levels of Beclin, Atg-3 and Atg-5 and reduced expression
levels of p62 and decreased signaling of the phosphoinositide-3
kinase/Akt/mammalian target of rapamycin and the p38 mitogen-activated protein
kinase pathways. Taken together, these findings may assist in the development of
novel chemotherapeutic agents for the treatment of malignant types of liver
cancer.
PMID- 25847491
TI - Ground to conduct: mechanochemical synthesis of a metal-organic framework with
high proton conductivity.
AB - We report a high proton-conducting material prepared for the first time by
economical and environmentally-friendly mechanochemistry. Structural elucidation
of the material from powder X-ray diffraction data reveals the details of the
solid-state reaction. The reaction represents a new synthetic strategy towards
materials related to fuel cell technology.
PMID- 25847496
TI - Editorial comment: Peyronie's disease and autoimmunity-a real-life clinical study
and comprehensive review.
PMID- 25847497
TI - A decade of research using the CASP scale: key findings and future directions.
AB - Since the publication of A Measure of Quality of Life in Early Old Age: The
Theory, Development and Properties of a Needs Satisfaction Model (CASP-19) just
over 10 years ago, the scale has gone on to be used in a wide variety of studies
in over 20 countries across the world and the original paper has become the most
highly cited paper for Aging and Mental Health. Therefore it was felt that it was
a good time to look back and reflect on the developments in the use of the scale
as well as to look forward to what new research is being done and could be done
with the measure. To this end we are extremely grateful for the editors for
allowing us to bring together a collection of papers that represent cutting edge
research using the CASP scale. These papers cover a wide variety of issues, from
working conditions to religiosity, from a range of countries, covering Western
and Eastern Europe as well as Africa. Each makes an important individual
contribution to our understanding of the factors that influence quality of life
in later life as well as pointing to the limitations of the measure and future
work that can be done in this area.
PMID- 25847499
TI - Functional role of water in membranes updated: A tribute to Trauble.
AB - The classical view of a cell membrane is as a hydrophobic slab in which only
nonpolar solutes can dissolve and permeate. However, water-soluble non
electrolytes such as glycerol, erythritol, urea and others can permeate lipid
membranes in the liquid crystalline state. Moreover, recently polar amino acid's
penetration has been explained by means of molecular dynamics in which appearance
of water pockets is postulated. According to Trauble (1971), water diffuses
across the lipid membranes by occupying holes formed in the lipid matrix due to
fluctuations of the acyl chain trans-gauche isomers. These holes, named "kinks"
have the molecular dimension of CH2 vacancies. The condensation of kinks may form
aqueous spaces into which molecular species of the size of low molecular weight
can dissolve. This molecular view can explain permeability properties considering
that water may be distributed along the hydrocarbon chains in the lipid matrix.
The purpose of this review is to consolidate the mechanism anticipated by Trauble
by discussing recent data in literature that directly correlates the molecular
state of methylene groups of the lipids with the state of water in each of them.
In addition, the structural properties of water near the lipid residues can be
related with the water activity triggering kink formation by changes in the head
group conformation that induces the propagation along the acyl chains and hence
to the diffusion of water.
PMID- 25847500
TI - The effectiveness of lung cancer MDT and the role of respiratory physicians.
AB - There is an increasing trend for the use of multi-disciplinary teams (MDT) in the
management of complex medical conditions. The latter may include various cancers,
including lung cancer. However, the use of MDT is not restricted to cancer
management, but may include complex conditions like diabetes and other non
malignant disorders. There is an increasing trend to use MDT in the investigation
and management of patients with suspected or proven lung cancer. This review
examines the evidence that supports the efficacy, or otherwise, of lung cancer
management in a MDT as opposed to individual care, who should be a member of a
lung cancer MDT, and the specific role of the respiratory physician in a lung
cancer MDT. Although it may seem to make common sense to manage lung cancer in a
MDT setting, there is actually little in the way of high quality data to support
this concept. The logistic and ethical difficulties in researching this issue are
highlighted in this review.
PMID- 25847501
TI - Current and future status of the use of transgenes for pest management.
PMID- 25847498
TI - Functional mechanisms of neurotransmitter transporters regulated by lipid-protein
interactions of their terminal loops.
AB - The physiological functions of neurotransmitter:sodium symporters (NSS) in
reuptake of neurotransmitters from the synapse into the presynaptic nerve have
been shown to be complemented by their involvement, together with non-plasma
membrane neurotransmitter transporters, in the reverse transport of substrate
(efflux) in response to psychostimulants. Recent experimental evidence implicates
highly anionic phosphatidylinositol 4,5-biphosphate (PIP(2)) lipids in such
functions of the serotonin (SERT) and dopamine (DAT) transporters. Thus, for both
SERT and DAT, neurotransmitter efflux has been shown to be strongly regulated by
the presence of PIP(2) lipids in the plasma membrane, and the electrostatic
interaction of the N-terminal region of DAT with the negatively charged PIP(2)
lipids. We examine the experimentally established phenotypes in a structural
context obtained from computational modeling based on recent crystallographic
data. The results are shown to set the stage for a mechanistic understanding of
physiological actions of neurotransmitter transporters in the NSS family of
membrane proteins. This article is part of a Special Issue entitled: Lipid
protein interactions.
PMID- 25847502
TI - Analysis of phenazepam and 3-hydroxyphenazepam in post-mortem fluids and tissues.
AB - Phenazepam is a benzodiazepine that is predominantly used clinically in the
former Soviet states but is being abused throughout the wider world. This study
reports the tissue distribution and concentration of both phenazepam and 3
hydroxyphenazepam in 29 cases quantitated by liquid chromatography-tandem mass
spectrometry (LC-MS/MS) in a variety of post-mortem fluids (subclavian blood,
femoral blood, cardiac blood, urine, vitreous humour) and tissues (thalamus,
liver and psoas muscle). In 27 cases, the cause of death was not directly related
to phenazepam (preserved (fluoride/oxalate) femoral blood phenazepam
concentrations 0.007 mg/L to 0.360 mg/L (median 0.097 mg/L). In two cases,
phenazepam was either a contributing factor to, or the certified cause of death
(preserved (fluoride/oxalate) femoral blood 0.97 mg/L and 1.64 mg/L). The
analysis of phenazepam and 3-hydroxyphenazepam in this study suggests that they
are unlikely to be subject to large post-mortem redistribution and that there is
no direct correlation between tissues/fluid and femoral blood concentrations.
Preliminary investigations of phenazepam stability comparing femoral blood
phenazepam concentrations in paired preserved (2.5% fluoride/oxalate) and
unpreserved blood show that unpreserved samples show on average a 14% lower
concentration of phenazepam and we recommend that phenazepam quantitation is
carried out using preserved samples wherever possible.
PMID- 25847503
TI - Autologous platelet-rich gel for treatment of diabetic chronic refractory
cutaneous ulcers: A prospective, randomized clinical trial.
AB - The purpose of the study is to examine the safety and effectiveness of topical
autologous platelet-rich gel (APG) application on facilitating the healing of
diabetic chronic refractory cutaneous ulcers. The study was designed as a
prospective, randomized controlled trial between January 1, 2007 and December 31,
2011. Eligible inpatients at the Diabetic Foot Care Center of West China
Hospital, Sichuan University (China) were randomly prescribed with a 12-week
standard treatment of ulcers (the control group) or standard treatment plus
topical application APG (the APG group). The wound healing grades (primary
endpoint), time to complete healing, and healing velocity within 12 weeks were
monitored as short-term effectiveness measurements, while side effects were
documented safety endpoints. The rates of survival and recurrence within the
follow up were recorded as long-term effectiveness endpoints. Analysis on total
diabetic ulcers (DUs) (n = 117) and subgroup analysis on diabetic foot ulcers
(DFUs) (n = 103) were both conducted. Standard treatment plus APG treatment was
statistically more effective than standard treatment (p < 0.05 in both total DUs
and subgroup of DFUs). The subjects defined as healing grade 1 were 50/59 (84.8%)
in total DUs and 41/48 (85.4%) in DFUs in the APG group compared with 40/58
(69.0%) and 37/55 (67.3%) in the control group from intent to treat population.
The Kaplan-Meier time-to-healing were significantly different between the two
groups (p < 0.05 in both total DUs and subgroup of DFUs). No side effects were
identified after topical APG application. The long-term survival and recurrence
rates were comparative between groups (p > 0.05). This study shows that topical
APG application plus standard treatment is safe and quite effective on diabetic
chronic refractory cutaneous ulcers, compared with standard treatment.
PMID- 25847504
TI - The effects of alpha-lipoic acid on breast of female albino rats exposed to
malathion: Histopathological and immunohistochemical study.
AB - BACKGROUND: The wide use of the organophosphate insecticide malathion is
accompanied by the risk of human exposure and may be involved in the etiology of
breast cancers, especially in developing countries. Alpha (alpha)-lipoic acid, a
natural molecule, present in our diet has antioxidant and protective effects in
cases such as aging, diabetes mellitus, and vascular and neurodegenerative
diseases all in which free radicals are involved. However, there is only scarce
data regarding the efficacy and biological activity of alpha-lipoic acid on
malathion-induced breast histopathological changes. AIMS: To investigate whether
malathion can induce mammary histopathological changes, to immunohistochemically
analyze the modulations in proliferation-apoptosis balance associated with these
changes, to assess the associated metabolic parameters, antioxidant stress and
hormonal profile changes and to elucidate the possible protective effect of alpha
lipoic acid on malathion induced alterations in rats. MATERIALS AND METHODS:
Forty Wistar female rats weighing 150-170g were divided into four groups. Group
1: control group were injected intraperitoneally (ip) with saline solution.
Group2: animals were injected (ip) with malathion twice a day for five days.
Group 3: animals were orally given alpha-lipoic acid, after three hours of
treatment with malathion at the same dose given to group 2. Group 4: animals were
treated with alpha-lipoic acid at the same dose given to group 3. Rats were
sacrificed on the 90th day, and breast tissues were analyzed for
histopathological and immunohistochemical alterations. Blood samples were
collected for biochemical tests. RESULTS: alpha-Lipoic acid exhibited a striking
reduction of malathion-induced mammary tumor incidence, and reversed intra-tumor
histopathological alterations. Alpha lipoic acid suppressed proliferating cell
nuclear antigen (PCNA) and p53 expression, induced apoptosis, upregulated
proapoptotic protein Bax. CONCLUSIONS: Our results provide the experimental
evidence that alpha-lipoic acid exerts chemopreventive effect in the breast
hyperplastic and malignant changes by suppressing abnormal cell proliferation and
inducing apoptosis with an oncostatic effects during an early-stage breast
cancer.
PMID- 25847505
TI - Respiratory syncytial virus infection of airway cells: Role of microRNAs.
AB - MicroRNAs (miRNAs) are small single-stranded RNA molecules involved in the
regulation of gene expression at the post-transcriptional level. In the airways,
miRNAs are implicated in the modulation of antiviral defense, through modulation
of both innate and adaptive immune response in inflammatory and immune effector
cells but also in parenchymal cells. The first target of respiratory viruses are
airway epithelial cells. Following infection, an altered expression of distinct
miRNAs occurs in airway cells aimed at inhibiting viral replication and
preserving the airway epithelial barrier, while at the same time viruses induce
or repress the expression of other miRNAs that favor viral replication.
Understanding the changes in miRNA expression profile, identification of miRNAs
target genes and their contribution to the pathogenesis of the disease may help
the intricate mechanisms of virus-host interaction. Further understanding of
these molecular mechanisms could lead to development of new antiviral treatments
in common, high impact, respiratory disorders for which specific treatments are
not available. Respiratory syncytial virus (RSV) airway infection is a common
example of virus modifying miRNAs expression to favor immune evasion, and
constitutes the salient feature of this review.
PMID- 25847506
TI - Hyperoxia-induced preconditioning against renal ischemic injury is mediated by
reactive oxygen species but not related to heat shock proteins 70 and 32.
AB - OBJECTIVE: Pre-exposure of rats to normobaric hyperoxia (O2 >= 95%) may induce
late preconditioning against renal ischemia-reperfusion (IR) injury. In this
study we investigated probable mechanisms of IR injury such as the role of
reactive oxygen species (ROS), renal antioxidant agents, and heat shock proteins
(HSP) 32 and 70 during delayed hyperoxia-preconditioning (HO). METHODS: Fifty-two
rats were divided into 7 groups: (A) IR, (B) HO + IR, (C) mercaptopropionyl
glycine (MPG) + HO + IR, (D) MPG + IR, (E) HO + sham, (F) MPG + sham, and (G)
sham. Rats in the following study groups (group B, C and E) were kept in a
normobaric hyperoxic environment for 4 h/day for 6 consecutive days, after which
they were subjected to 40 minutes of ischemia; animals in the control group
(group A, D, F, and G) were kept in a normoxic cage. At the end of the
preconditioning period, 24 hours of reperfusion was performed. Renal function was
assessed by measuring serum creatinine (Cr), blood urea nitrogen (BUN), and
creatinine clearance (CLCr). Induction of the antioxidant system was evaluated by
measuring renal catalase (CAT) and superoxide dismutase (SOD) activities and
glutathione (GSH) and malondialdehyde (MDA) content. The role of ROS was
investigated by use of MPG (a ROS scavenger). HSP32 & 70 mRNA and protein also
were determined. RESULTS: The hyperoxia-preconditioned IR group (B) had a lower
plasma Cr and BUN and greater CLCr compared with the IR group (A) (P <= .016).
Administration of MPG led to an increase in plasma Cr and BUN and a decrease in
CLCr in group C compared with the hyperoxia-preconditioned group B (P <= .004).
The hyperoxia-preconditioned IR group had a greater CAT activity and GSH level
compared with the IR group A (P <= .007), whereas the administration of MPG did
not change the GSH level but led to a decrease in CAT activity in group D
compared with group B (P < .001). SOD activity did not change in hyperoxia
preconditioned ischemic rats compared with ischemic rats. Hyperoxia
preconditioning and MPG administration in ischemic animals did not result in any
considerable change in MDA level compared with the IR group A. Also, there were
no clinically relevant differences in HSP32 & 70 mRNA and protein between all
groups. CONCLUSION: The present study demonstrates that repeated pre-exposure to
hyperoxia can decrease subsequent renal IR damage in this rat model of renal
ischemia. Free radical production after hyperoxia appears to play a pivotal role
in the hyperoxia-induced renal protection independent of HSP level. Antioxidant
enzyme activities and especially catalase seem to be implicated in this renal
protective mechanism.
PMID- 25847508
TI - Feature Page.
PMID- 25847507
TI - The association of single nucleotide polymorphisms in the connective tissue
growth factor gene with pseudoexfoliation syndrome/glaucoma.
PMID- 25847509
TI - Sofosbuvir plus pegylated interferon and ribavirin in patients with genotype 1
hepatitis C virus in whom previous therapy with direct-acting antivirals has
failed.
AB - Retreatment of patients who have not achieved sustained virological response
(SVR) after treatment with investigational direct-acting antiviral agents (DAAs)
has not been extensively studied. We conducted an open-label trial to assess the
efficacy and safety of sofosbuvir (SOF) plus pegylated interferon (Peg-IFN) and
ribavirin (RBV) in patients with genotype 1 hepatitis C virus (HCV) who
participated in previous studies of one or more Gilead investigational DAAs in
combination with RBV with or without Peg-IFN. We enrolled 80 patients at 40
sites. All patients received SOF 400 mg once daily plus Peg-IFN-alpha 180
MUg/week and weight-based ribavirin (1,000 or 1,200 mg/day) for 12 weeks. The
efficacy endpoint was the proportion of patients with SVR 12 weeks after
discontinuation of therapy (SVR12). Of the 80 patients enrolled, 36 (45%) had
received two or more courses of earlier treatment for HCV and 74 (93%) had at
least one resistance-associated variant (RAV) at baseline. SVR12 was achieved by
63 of the 80 patients (79%) treated. Rates of SVR12 were similar across patient
subgroups. Presence of RAVs at baseline did not appear to be associated with
treatment failure. Seventy-one of eighty patients (89%) experienced at least one
adverse event (AE), but most events were mild to moderate in severity. The most
common AEs were fatigue, headache, and nausea. No patients discontinued all
treatment because of AEs. CONCLUSION: These findings suggest that SOF plus Peg
IFN and RBV for 12 weeks is effective and safe in patients who have not achieved
SVR with earlier regimens of one or more DAAs plus Peg-IFN and RBV.
PMID- 25847511
TI - SOX7 interferes with beta-catenin activity to promote neuronal apoptosis.
AB - SOX7 mediates various developmental processes. However, its role in neuronal
apoptosis remains unclear. In the present study, we investigated the expression
pattern and role of SOX7 in potassium deprivation-induced rat cerebellar granule
neuron apoptosis. Our results showed that both mRNA and protein levels of SOX7
were upregulated when potassium was deprived. SOX7 overexpression promoted
neuronal apoptosis, whereas knockdown of SOX7 protected neurons against
apoptosis. Moreover, we found that beta-catenin activity was suppressed during
apoptosis and that beta-catenin inhibition was crucial for potassium deprivation
induced neuronal apoptosis. This suppression was mediated by an interaction
between SOX7 and beta-catenin but not by protein degradation. Lastly, we showed
that beta-catenin inhibition mediated the pro-apoptotic effect of SOX7. Together,
our findings demonstrated that SOX7 interfered with beta-catenin activity to
promote neuronal apoptosis, which acted as a novel signaling mechanism in
neuronal cell death.
PMID- 25847510
TI - Respiratory syncytial virus, an ongoing medical dilemma: an expert commentary on
respiratory syncytial virus prophylactic and therapeutic pharmaceuticals
currently in clinical trials.
AB - As the most important viral cause of severe respiratory disease in infants and
increasing recognition as important in the elderly and immunocompromised,
respiratory syncytial virus (RSV) is responsible for a massive health burden
worldwide. Prophylactic antibodies were successfully developed against RSV.
However, their use is restricted to a small group of infants considered at high
risk of severe RSV disease. There is still no specific therapeutics or vaccines
to combat RSV. As such, it remains a major unmet medical need for most
individuals. The World Health Organisations International Clinical Trials
Registry Platform (WHO ICTRP) and PubMed were used to identify and review all RSV
vaccine, prophylactic and therapeutic candidates currently in clinical trials.
This review presents an expert commentary on all RSV-specific prophylactic and
therapeutic candidates that have entered clinical trials since 2008.
PMID- 25847513
TI - Assessing the drug release from nanoparticles: Overcoming the shortcomings of
dialysis by using novel optical techniques and a mathematical model.
AB - The aim of the present investigation was to develop a reliable method which can
be applied to the measurement of in vitro drug release from nanocarriers. Since
the limited membrane transport is one major obstacle to the assessment of drug
release with dialysis techniques, the determination of this parameter was our
objective. Therefore, a novel drug release automatic monitoring system (DREAMS)
was designed to conduct continuous measurements during the dialysis process.
Moreover, a mathematical model was used for evaluation of the experimental data.
This combination of mathematical and analytical tools enabled the quantification
of the total amount of free drug in the system. Eudragit((r)) RS 100
nanoparticles loaded with the model compound 5,10,15,20-tetrakis(m
hydroxypheny)chlorin (mTHPC) were investigated and the drug release was
continuously monitored by using a fluorescence spectrometer that is part of the
setup. Free drug and drug-loaded nanoparticles were tested to discriminate
between the two formulations. In addition, two types of membranes composed of
different materials were evaluated and the kinetics of membrane transport was
determined. The data obtained from the apparatus were further treated by a
mathematical model, which yielded distinguishable release profiles between
samples of different compositions. The method offers a promising option for
release testing of nanoparticles.
PMID- 25847514
TI - Military sexual assault, gender, and PTSD treatment outcomes of U.S. Veterans.
AB - This study examined whether gender and military sexual assault (MSA) were
associated with psychiatric severity differences at initiation of treatment for
posttraumatic stress disorder (PTSD) and whether MSA and gender predicted
psychiatric treatment outcomes. Male (n = 726) and female (n = 111) patients were
recruited from 7 U.S. Department of Veterans Affairs (VA) PTSD specialty
intensive treatment programs and completed an intake survey; 69% (n = 574) of the
participants completed a 4-month postdischarge follow-up survey. Measures
included current PTSD and depressive symptoms, aggressive/violent behaviors,
alcohol and drug use severity, and quality of life. Multilevel multivariate
regression analyses were conducted to examine the main and interaction effects of
gender and MSA on psychiatric treatment outcomes at 4-month follow-up, including
demographics, baseline severity, hostile fire, and treatment length of stay.
Baseline PTSD severity did not differ by gender or MSA status, but women had more
severe depressive symptoms (d = 0.40) and less aggressive/violent symptoms (d =
0.46) than men. Gender, MSA status, and the interaction between gender and MSA
did not predict treatment outcomes as hypothesized. Male and female veterans with
and without MSA responded equally well to treatment in VA PTSD intensive
treatment programs.
PMID- 25847515
TI - Management of massive bone loss in infected reverse shoulder arthroplasty using
an articulating hip antibiotic spacer: a case report.
PMID- 25847512
TI - Accuracy of multiecho magnitude-based MRI (M-MRI) for estimation of hepatic
proton density fat fraction (PDFF) in children.
AB - PURPOSE: To assess accuracy of magnitude-based magnetic resonance imaging (M-MRI)
in children to estimate hepatic proton density fat fraction (PDFF) using two to
six echoes, with magnetic resonance spectroscopy (MRS) -measured PDFF as a
reference standard. METHODS: This was an IRB-approved, HIPAA-compliant, single
center, cross-sectional, retrospective analysis of data collected prospectively
between 2008 and 2013 in children with known or suspected nonalcoholic fatty
liver disease (NAFLD). Two hundred eighty-six children (8-20 [mean 14.2 +/- 2.5]
years; 182 boys) underwent same-day MRS and M-MRI. Unenhanced two-dimensional
axial spoiled gradient-recalled-echo images at six echo times were obtained at 3T
after a single low-flip-angle (10 degrees ) excitation with >= 120-ms recovery
time. Hepatic PDFF was estimated using the first two, three, four, five, and all
six echoes. For each number of echoes, accuracy of M-MRI to estimate PDFF was
assessed by linear regression with MRS-PDFF as reference standard. Accuracy
metrics were regression intercept, slope, average bias, and R(2) . RESULTS: MRS
PDFF ranged from 0.2-40.4% (mean 13.1 +/- 9.8%). Using three to six echoes,
regression intercept, slope, and average bias were 0.46-0.96%, 0.99-1.01, and
0.57-0.89%, respectively. Using two echoes, these values were 2.98%, 0.97, and
2.72%, respectively. R(2) ranged 0.98-0.99 for all methods. CONCLUSION: Using
three to six echoes, M-MRI has high accuracy for hepatic PDFF estimation in
children.
PMID- 25847516
TI - Biomechanical comparison between the trapezius transfer and latissimus transfer
for irreparable posterosuperior rotator cuff tears.
AB - BACKGROUND: The purpose of this study was to characterize the biomechanical
effects of the lower trapezius transfer and to compare it with the latissimus
dorsi transfer in a cadaveric model of a massive posterosuperior rotator cuff
tear. METHODS: Eight cadaveric shoulders were tested at 0 degrees , 30 degrees ,
and 60 degrees of shoulder abduction. Range of motion, humeral rotational
position due to muscle loading, joint reaction forces, and kinematics were
measured. All specimens were tested in 4 conditions: intact, massive
posterosuperior cuff tear, lower trapezius transfer, and latissimus dorsi
transfer. A repeated-measures analysis of variance was used for statistical
analysis. RESULTS: Internal rotation due to muscle loading increased with massive
cuff tear compared with the intact condition (P < .05). The latissimus transfer
corrected this change at 0 degrees abduction, whereas the trapezius transfer
corrected this at all abduction angles. The massive cuff tear decreased
glenohumeral joint compression forces at all abduction angles; these forces were
restored by the lower trapezius transfer (P < .05). At maximum humeral internal
rotation and 0 degrees of abduction, the humeral head apex shifted superiorly
and laterally with massive cuff tear (P < .05); this shift was more closely
restored to intact values by the trapezius transfer compared with the latissimus
transfer (P < .05). CONCLUSION: The lower trapezius transfer is superior to the
latissimus transfer at restoring native glenohumeral kinematics and joint
reaction forces in our cadaveric model. It may be a promising treatment option
for patients with a massive irreparable rotator cuff tear.
PMID- 25847517
TI - The significance of the clavicle on shoulder girdle function.
AB - BACKGROUND: Patients with cleidocranial dysplasia (CCD) can have a congenital
partial or total absence of the clavicle. The aim of this study was to evaluate
the functional shoulder score in these patients. MATERIAL AND METHODS: Patients
with CCD who were members of a social media group were invited to take part in an
Internet-based survey. The questionnaire was composed of 3 general questions, a
question concerning partial or total absence of the clavicle, and 3 patient-based
shoulder scores (American Shoulder and Elbow Surgeons score; shortened
Disabilities of the Arm, Shoulder, and Hand score; and patient-based Constant
Murley score). RESULTS: Thirty-six patients (27 women, 9 men) with a mean age of
40 years participated in the survey; 17 patients had a bilateral absence, 16
patients had a bilateral partial absence, and 3 patients had a total absence on
one side and a partial absence of the clavicle on the other side. The average
patient-based Constant-Murley score was 79; shortened Disabilities of the Arm,
Shoulder, and Hand score, 11; and American Shoulder and Elbow Surgeons score, 93.
There was no significant difference in the scores between left and right. There
was no correlation between partial and total absences and the shoulder scores.
CONCLUSION: Patients with self-reported CCD are subjectively normal to their
peers when they are evaluated with 3 common shoulder scores. There was no
correlation between partial and total absences and the shoulder scores.
PMID- 25847518
TI - Medical procedures and outcomes of Japanese patients with trisomy 18 or trisomy
13: analysis of a nationwide administrative database of hospitalized patients.
AB - The choices of aggressive treatment for trisomy 18 (T18) and trisomy 13 (T13)
remain controversial. Here, we describe the current medical procedures and
outcomes of patients with T18 and T13 from a nationwide administrative database
of hospitalized patients in Japan. We used the database to identify eligible
patients with T18 (n = 438) and T13 (n = 133) who were first admitted to one of
200 hospitals between July 2010 and March 2013. Patients were divided into
admission at day <7 (early neonatal) and admission at day >=7 (late neonatal and
post neonatal) groups, and we described the medical intervention and status at
discharge for each group. In the day <7 groups, surgical interventions were
performed for 56 (19.9%) T18 patients and 22 (34.4%) T13 patients, including
pulmonary artery banding, and procedures for esophageal atresia and omphalocele.
None received intracardiac surgery. The rate of patients discharged to home was
higher in the day >=7 groups than the day <7 groups (T18: 72.6 vs. 38.8%; T13:
73.9 vs. 21.9%, respectively). Our data show that a substantial number of
patients with trisomy received surgery and were then discharged home, but, of
these, a considerable number required home medical care. This included home
oxygen therapy, home mechanical ventilation, and tube feeding. These findings
will be useful to clinicians or families who care for patients with T18 and T13.
PMID- 25847520
TI - ISSCR 2013: back to Bean Town.
AB - The International Society for Stem Cell Research 11(th) Annual Meeting was held
in Boston in June 2013, bringing together just over 4000 attendees. An emphasis
on therapeutic applications in many talks reflected the maturation of the stem
cell field from its origins in basic science to one that is beginning to show
therapeutic promise.
PMID- 25847521
TI - Stem cells in translation: impression of the ISSCR Regional Meeting in Florence.
AB - The International Society for Stem Cell Research hosted an exciting meeting on
stem cell-based translational medicine in Florence, Italy in September 2013. This
report gives an overview of recent advances and breakthroughs presented at the
meeting.
PMID- 25847522
TI - Microbial ecology of watery kimchi.
AB - The biochemistry and microbial ecology of 2 similar types of watery (mul) kimchi,
containing sliced and unsliced radish and vegetables (nabak and dongchimi,
respectively), were investigated. Samples from kimchi were fermented at 4, 10,
and 20 degrees C were analyzed by plating on differential and selective media,
high-performance liquid chromatography, and high-throughput DNA sequencing of 16S
rDNA. Nabak kimchi showed similar trends as dongchimi, with increasing lactic and
acetic acids and decreasing pH for each temperature, but differences in
microbiota were apparent. Interestingly, bacteria from the Proteobacterium
phylum, including Enterobacteriaceae, decreased more rapidly during fermentation
at 4 degrees C in nabak cabbage fermentations compared with dongchimi. Although
changes for Proteobacterium and Enterobacteriaceae populations were similar
during fermentation at 10 and 20 degrees C, the homolactic stage of fermentation
did not develop for the 4 and 10 degrees C samples of both nabak and dongchimi
during the experiment. These data show the differences in biochemistry and
microbial ecology that can result from preparation method and fermentation
conditions of the kimchi, which may impact safety (Enterobacteriaceae populations
may include pathogenic bacteria) and quality (homolactic fermentation can be
undesirable, if too much acid is produced) of the product. In addition, the data
also illustrate the need for improved methods for identifying and differentiating
closely related lactic acid bacteria species using high-throughput sequencing
methods.
PMID- 25847523
TI - Equivocal ALK fluorescence in-situ hybridization (FISH) cases may benefit from
ancillary ALK FISH probe testing.
AB - AIMS: Accurate assessment of anaplastic lymphoma kinase (ALK) gene rearrangement
in non-small-cell lung cancers (NSCLCs) is critical to identify patients who are
likely to respond to crizotinib. The aim of this study was to evaluate the
ALK/EML4 TriCheck FISH probe in a series of NSCLCs enriched for tumours with
equivocal ALK status. METHODS AND RESULTS: ALK FISH was prospectively performed
on 45 NSCLCs with the ALK/EML4 TriCheck probe (ZytoVision) and the Vysis ALK
break-apart probe (Abbott Molecular). ALK immunohistochemistry was performed with
5A4 and D5F3 antibodies. Fourteen cases had equivocal ALK status, based on
borderline or focal FISH positivity, an atypical FISH pattern, or discrepancy
between ALK FISH and immunohistochemistry. Four of the 14 equivocal cases showed
discordance between the two FISH probes. All other cases were concordant. The
TriCheck probe showed that, of 31 unequivocal cases, 15 were ALK-rearranged, and
60% of these had EML4 as the translocation partner. Within the group of 14
equivocal cases, 12 showed rearrangement with the Tricheck probe; only one of
these showed EML4 rearrangement. Of the six equivocal cases that received
crizotinib, four showed clinical benefit. CONCLUSIONS: The ALK/EML4 TriCheck FISH
probe may be useful for the detection of ALK rearrangements, especially in
borderline or atypical cases, where an additional unique ALK FISH probe may
provide further confirmation of rearrangement.
PMID- 25847525
TI - Hysterectomy with radiotherapy or chemotherapy or both for women with locally
advanced cervical cancer.
AB - BACKGROUND: Cervical cancer is the second commonest cancer among women up to 65
years of age and is the most frequent cause of death from gynaecological cancers
worldwide. Sources suggest that a very high proportion of new cervical cancer
cases in developing countries are at an advanced stage (IB2 or more) and more
than a half of these may be stage III or IV. Cervical cancer staging is based on
findings from clinical examination (FIGO) staging). Standard care in Europe and
US for stage IB2 to III is non-surgical treatment (chemoradiation). However in
developing countries, where there is limited access to radiotherapy, locally
advanced cervical cancer may be treated with a combination of chemotherapy and
hysterectomy (surgery to remove the womb and the neck of the womb, with or
without the surrounding tissues). It is not certain if this improves survival.
Therefore, it is important to systematically assess the value of hysterectomy in
addition to radiotherapy or chemotherapy, or both, as an alternative intervention
in the treatment of locally advanced cervical cancer (stage IB2 to III).
OBJECTIVES: To determine whether hysterectomy, in addition to standard treatment
with radiation or chemotherapy, or both, in women with locally advanced cervical
cancer (stage IB2 to III) is safe and effective compared with standard treatment
alone. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group
Trials Register, CENTRAL, MEDLINE, EMBASE and LILACS up to February 2014. We also
searched registers of clinical trials, abstracts of scientific meetings and
reference lists of included studies. SELECTION CRITERIA: We searched for
randomised controlled trials (RCTs) that compared treatment protocols involving
hysterectomy versus radiotherapy or chemotherapy, or both, in women with advanced
stage (IB2 to III) cervical cancer presenting for the first time. DATA COLLECTION
AND ANALYSIS: We assessed study eligibility independently, extracted data and
assessed risk of bias. Where possible, overall and progression or disease-free
survival outcomes were synthesised in a meta-analysis using the random-effects
model. Adverse events were incompletely reported so results of single trials were
described in narrative form. MAIN RESULTS: We included seven RCTs (1217 women) of
varying methodological quality in the review; most trials were at moderate or
high risk of bias.Three were multi-centre trials, two were single-centre trials,
and in two trials it was unclear if they were single or multi-centre. These
trials compared the following interventions for women with locally advanced
cervical cancer (stages IB2 to III):hysterectomy (simple or radical) with
radiotherapy (N = 194) versus radiotherapy alone (N = 180); hysterectomy (simple
or radical) with chemoradiotherapy (N = 31) versus chemoradiotherapy alone (N =
30); hysterectomy (radical) with chemoradiotherapy (N = 111) versus internal
radiotherapy with chemoradiotherapy (N = 100); hysterectomy (simple or radical)
with upfront (neoadjuvant) chemotherapy (N = 298) versus radiotherapy alone (N =
273).One trial (N = 256) found no difference in the risk of death or disease
progression between women who received attenuated radiotherapy followed by
hysterectomy and those who received radiotherapy (external and internal) alone
(hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.61 to 1.29). This trial
also reported no difference between the two groups in terms of adverse effects
(18/129 grade 3 or 4 adverse effects in the hysterectomy and radiation group and
19 cases in 18/121 women in the radiotherapy alone group). There was no
difference in 5-year tumour-free actuarial survival (representation of the
probable years of survivorship of a defined population of participants) or severe
complications (grade 3) in another trial (N = 118) which reported the same
comparison (6/62 versus 6/56 in the radiation with surgery group versus the
radiotherapy alone group, respectively). The quality of the evidence was low for
all these outcomes.One trial (N = 61) reported no difference (P value > 0.10) in
overall and recurrence-free survival at 3 years between chemoradiotherapy and
hysterectomy versus chemoradiotherapy alone (low quality evidence). Adverse
events and morbidity data were not reported.Similarly, another trial (N = 211)
found no difference in the risk of death (HR 0.65, 95% CI 0.35 to 1.21, P value =
0.19, low quality evidence), disease progression (HR 0.70, 95% CI 0.31 to 1.34, P
value = 0.24, low quality evidence) or severe late complications (P value = 0.53,
low quality evidence) between women who received internal radiotherapy versus
hysterectomy after both groups had received external-beam chemoradiotherapy.Meta
analysis of three trials of neoadjuvant chemotherapy and hysterectomy versus
radiotherapy alone, assessing 571 participants, found that women who received
neoadjuvant chemotherapy plus hysterectomy had less risk of death than those who
received radiotherapy alone (HR 0.71, 95% CI 0.55 to 0.93, I(2) = 0%, moderate
quality evidence). However, a significant number of the participants that
received neoadjuvant chemotherapy plus hysterectomy had radiotherapy as well.
There was no difference in the proportion of women with disease progression or
recurrence between the two groups (RR 0.75, 95% CI 0.53 to 1.05, I(2) = 20%,
moderate quality evidence).Results of single trials reported no apparent (P value
> 0.05) difference in long-term severe complications, grade 3 acute toxicity and
severe late toxicity between the two groups (low quality evidence).Quality of
life outcomes were not reported in any of the trials. AUTHORS' CONCLUSIONS: From
the available RCTs, we found insufficient evidence that hysterectomy with
radiotherapy, with or without chemotherapy, improves the survival of women with
locally advanced cervical cancer who are treated with radiotherapy or
chemoradiotherapy alone. The overall quality of the evidence was variable across
the different outcomes and was universally downgraded due to concerns about risk
of bias. The quality of the evidence for neoadjuvant chemotherapy and radical
hysterectomy versus radiotherapy alone for survival outcomes was moderate, with
evidence from other comparisons of low quality. This was mainly based on poor
reporting and sparseness of data where results were based on single trials. More
trials that assess medical management with and without hysterectomy may test the
robustness of the findings of this review as further research is likely to have
an important impact on our confidence in the estimate of effect.
PMID- 25847524
TI - Presenting phenotype of paediatric inflammatory bowel disease in Wessex, Southern
England 2010-2013.
AB - AIM: There has been at least a twofold increase in the incidence of paediatric
inflammatory bowel disease (PIBD) over the last 20 years; we report the
presenting features from 2010 to 2013 and compare with previous data. METHODS:
All patients diagnosed with PIBD at University Hospitals Southampton from 2010 to
2013 were identified from an in-house database. Data were obtained from paper and
electronic notes. Height, weight and BMI SDS are presented as median values (95%
CI). RESULTS: One hundred and seventy-two patients were included (median age at
diagnosis 13.5, 115 male); Crohn's disease (CD) - 107, UC - 50, inflammatory
bowel disease unclassified (IBDU) - 15. The most common presenting features of CD
were abdominal pain (86%), diarrhoea (78.5%) and weight loss (56.1%); 42.1% of
patients had all three. In UC blood in stool (92%), diarrhoea (92%) and abdominal
pain (88%) were the most common; all three in 76% of patients. CD presented with
ileocolonic disease in 52.5%. UC presented with pancolitis in 64%. There was
growth delay in CD: height -0.37 (-0.60 to -0.14); weight -1.09 (-1.35 to -0.83).
Growth was maintained in UC: height 0.53 (0.19 to 0.87); weight 0.14 (-0.20 to
0.48). CONCLUSION: Paediatric inflammatory bowel disease phenotype remains as
extensive despite increasing incidence. Although the classical phenotype is
common, a reasonable proportion present with atypical features, normal growth and
normal blood markers.
PMID- 25847519
TI - Epigenetics of the failing heart.
AB - With the impressive advancement in high-throughput 'omics' technologies over the
past two decades, epigenetic mechanisms have emerged as the regulatory interface
between the genome and environmental factors. These mechanisms include DNA
methylation, histone modifications, ATP-dependent chromatin remodeling and RNA
based mechanisms. Their highly interdependent and coordinated action modulates
the chromatin structure controlling access of the transcription machinery and
thereby regulating expression of target genes. Given the rather limited
proliferative capability of human cardiomyocytes, epigenetic regulation appears
to play a particularly important role in the myocardium. The highly dynamic
nature of the epigenome allows the heart to adapt to environmental challenges and
to respond quickly and properly to cardiac stress. It is now becoming evident
that histone-modifying and chromatin-remodeling enzymes as well as numerous non
coding RNAs play critical roles in cardiac development and function, while their
dysregulation contributes to the onset and development of pathological cardiac
remodeling culminating in HF. This review focuses on up-to-date knowledge about
the epigenetic mechanisms and highlights their emerging role in the healthy and
failing heart. Uncovering the determinants of epigenetic regulation holds great
promise to accelerate the development of successful new diagnostic and
therapeutic strategies in human cardiac disease.
PMID- 25847526
TI - Differential expression of ethylene biosynthesis genes in drupelets and
receptacle of raspberry (Rubus idaeus).
AB - Red Raspberry (Rubus idaeus) is traditionally classified as non-climacteric, and
the role of ethylene in fruit ripening is not clear. The available information
indicates that the receptacle, a modified stem that supports the drupelets, is
involved in ethylene production of ripe fruits. In this study, we report
receptacle-related ethylene biosynthesis during the ripening of fruits of cv.
Heritage. In addition, the expression pattern of ethylene biosynthesis
transcripts was evaluated during the ripening process. The major transcript
levels of 1-aminocyclopropane-1-carboxylic acid synthase (RiACS1) and 1
aminocyclopropane-1-carboxylic acid oxidase (RiACO1) were concomitant with
ethylene production, increased total soluble solids (TSS) and decreased
titratable acidity (TA) and fruit firmness. Moreover, ethylene biosynthesis and
transcript levels of RiACS1 and RiACO1 were higher in the receptacle, sustaining
the receptacle's role as a source of ethylene in regulating the ripening of
raspberry.
PMID- 25847527
TI - NIR Fluorogenic Dye as a Modular Platform for Prodrug Assembly: Real-Time in vivo
Monitoring of Drug Release.
AB - The ability to monitor drug release in vivo provides essential pharmacological
information. We developed a new modular approach for the preparation of
theranostic prodrugs with a turn-ON near-infrared (NIR) fluorescence mode of
action. The prodrugs release their chemotherapeutic cargo and an active cyanine
fluorophore upon reaction with a specific analyte. The prodrug platform is based
on the fluorogenic dye QCy7; upon removal of a triggering substrate, the dye
fluoresces, and the free drug is released. The evaluated camptothecin prodrug was
activated by endogenous hydrogen peroxide produced in tumor cells in vitro and in
vivo. Drug release and in vitro cytotoxicity were correlated with the emitted
fluorescence. The prodrug activation was effectively imaged in real time in mice
bearing tumors. The modular design of the QCy7 fluorogenic platform should allow
the preparation of numerous other prodrugs with various triggering substrates and
chemotherapeutic agents. We anticipate that the development of real-time in vivo
monitoring tools such as that described herein will pave the way for personalized
therapy.
PMID- 25847528
TI - Palladium-catalyzed enantioselective C-H arylation for the synthesis of P
stereogenic compounds.
AB - A palladium-catalyzed enantioselective C-H arylation of N-(o-bromoaryl)
diarylphosphinic amides is described for the synthesis of phosphorus compounds
bearing a P-stereogenic center. The method provides good enantioselectivities and
high yields. The products were readily transformed into P-chiral biphenyl
monophosphine ligands.
PMID- 25847529
TI - Suppressive effects of exogenous regucalcin on the proliferation of human
pancreatic cancer MIA PaCa-2 cells in vitro.
AB - Regucalcin plays a pivotal role as a suppressor protein in signal transduction in
various types of cells and tissues. The regucalcin gene is localized on the X
chromosome. and its expression has been shown to be suppressed in various types
of tumor tissue in animal and human subjects, suggesting a potential role of
regucalcin in carcinogenesis. This study was undertaken to determine the effects
of exogenous regucalcin on the proliferation of cloned human pancreatic cancer
MIA PaCa-2 cells in vitro. The proliferation of the MIA PaCa-2 cells was
suppressed following culture with regucalcin (0.01-10 nM). Such an effect was
also observed in pancreatic cancer Pt45P1 cells, that highly expressed tissue
factor (high TF), or Pt45P1 cells, that highly expressed alternativly spliced
variants of tissue factor (asTF). In the MIA PaCa-2 cells, the suppressive
effects of regucalcin on cell proliferation were not enhanced either in the
presence of tumor necrosis factor-alpha (TNF-alpha), or in the presence of Bay K
8644, PD98059, staurosporine, wortmannin or 5,6-dichloro-1-beta-D
ribofuranosylbenzimidazole (DRB). However, this was not the case for gemcitabine,
which was shown to suppress cell proliferation. Exogenous regucalcin did not
cause apoptotic cell death in the MIA PaCa-2 cells in vitro. These findings
demonstrate that exogenous regucalcin exerts suppressive effects on the
proliferation of human pancreatic MIA PaCa-2 cells and that these effects are
mediated through the inhibition of various signaling pathways related to nuclear
factor-kappaB (NF-kappaB), extracellular signal-regulated kinase (ERK), protein
kinase C, calcium signaling, phosphatidylinositol 3-kinase (PI3K) or nuclear
transcription activity in vitro. Our data suggest that exogenous regucalcin
exerts suppressive effects on the proliferation of human pancreatic cancer cells.
PMID- 25847530
TI - Comprehensive analysis of fatty alcohol ethoxylates by ultra high pressure
hydrophilic interaction chromatography coupled with ion mobility spectrometry
mass spectrometry using a custom-designed sub-2 MUm column.
AB - Comprehensive analysis of fatty alcohol ethoxylates has been conducted by
coupling ultra high pressure hydrophilic interaction chromatography and ion
mobility spectrometry mass spectrometry. A custom-designed sub-2 MUm column was
used for the chromatographic separation of fatty alcohol ethoxylates by
hydrophilic interaction chromatography. Ion mobility spectrometry provided a post
ionization resolution during a very short period of 6.4 ms. Distinguishable
families of singly, doubly, and triply charged fatty alcohol ethoxylates were
clearly observed. By virtue of the combination of hydrophilic interaction
chromatography and ion mobility spectrometry, comprehensive resolution based on
both hydrophobicity difference and mobility disparity has been achieved for fatty
alcohol ethoxylates. The orthogonality of the developed separation and analysis
system was evaluated with the correlation coefficient and peak spreading angle of
0.0224 and 88.72 degrees , respectively. The actual peak capacity obtained was
individually 40 and 193 times than those when hydrophilic interaction
chromatography and ion mobility spectrometry were used alone. The collision cross
sections of fatty alcohol ethoxylates were calculated by calibrating the
traveling wave ion mobility device with polyalanine.
PMID- 25847531
TI - 'I've used the word cancer but it's actually good news': discursive
performativity of cancer and the identity of urological cancer services.
AB - Drawing on the ethnographic study of urological cancer services, this article
explores how a set of particular discourses embedded in the everyday clinical
work in a large teaching hospital in the UK helps materialise particular
configurations of cancer and related professional identities. Emerging on the
intersection of specific socio-material arrangements (cancer survival rates,
treatment regimens, cancer staging classifications, metaphors, clinical
specialities) and operating across a number of differential relations
(curable/incurable, treatable/untreatable, aggressive/nonaggressive), these
configurations help constitute the categories of 'good' and 'bad' cancers as
separate and contrasting entities. These categories help materialise particular
distributions of power and are thus implicated in the making of specific claims
about the identity of urological cancer services as unique and privileged.
Exploring these issues in view of feminist and material-semiotic approaches to
studying science, technology and medicine, this article seeks to move away from
the understanding of cancer discourses as primarily linguistic performances,
proposing to see them instead as arrangements of practices and relations
simultaneously material and semiotic through which particular categories,
entities and phenomena acquire their determinate nature. In doing so, it seeks to
contribute to sociology's broader concern with discursive performativity of
cancer.
PMID- 25847532
TI - Living for the moment: men situating risk-taking after the death of a friend.
AB - The primary cause of death for men under the age of 30 is unintentional injury
and, despite health-promotion efforts and programme interventions, male injury
and death rates have not decreased in recent years. Drawing on 22 interviews from
a study of men, risk and grief, we describe how a risk-related tragedy shaped the
participants' understandings of and practices of risk-taking. The findings
indicate that most participants did not alter their perceptions and engagement in
risky practices, which reflected their alignment to masculine ideals within
specific communities of practice where risk-taking was normalised and valorised.
Continued reliance on risky practices following the death of a friend was
predominantly expressed as 'living for the moment,' where caution and safety were
framed as conservative practices that undermined and diluted the robustness
ideally embodied by this subgroup of young men. Two main themes: living life,
accepting death and upping the ante illustrate how risk-taking can persist
following a death. A smaller group of participants articulated a different
viewpoint; reining in risk practices, to describe their risk management
approaches after the death of a male friend. This novel study confirms the
ongoing challenge of reducing men's risk-taking practices, even after the death
of a friend.
PMID- 25847533
TI - Expectations in the field of the internet and health: an analysis of claims about
social networking sites in clinical literature.
AB - This article adopts a critical sociological perspective to examine the
expectations surrounding the uses of social networking sites (SNSs) articulated
in the domain of clinical literature. This emerging body of articles and
commentaries responds to the recent significant growth in SNS use, and
constitutes a venue in which the meanings of SNSs and their relation to health
are negotiated. Our analysis indicates how clinical writing configures the role
of SNSs in health care through a range of metaphorical constructions that frame
SNSs as a tool, a conduit for information and a traversable space. The use of
such metaphors serves not only to describe the new affordances offered by SNSs
but also posits distinct lay and professional practices, while reviving a range
of celebratory claims about the Internet and health critiqued in sociological
literature. These metaphorical descriptions characterise SNS content as
essentially controllable by autonomous users while reiterating existing arguments
that e-health is both inherently empowering and risky. Our analysis calls for a
close attention to these understandings of SNSs as they have the potential to
shape future online initiatives, most notably by anticipating successful
professional interventions while marginalising the factors that influence users'
online and offline practices and contexts.
PMID- 25847535
TI - Darier-White disease treated with fractional CO2 laser in two cases.
AB - Darier-White disease is one of the most common genodermatoses. The most typical
clinical symptoms such as diffuse hyperkeratotic papulae usually appear during
puberty or early adulthood in seborrhoeic area. It is connected with substantial
deterioration of the quality of life due to aesthetic defect. Although there
exist many therapeutic options, the disease still causes considerable therapeutic
difficulties. Treatment with fractional CO2 laser seems to be a promising
therapeutic method. In this paper, we present two cases of patients with Darier's
disease who have been treated with a fractional CO2 laser with very good clinical
outcome.
PMID- 25847536
TI - Failing to forget: inhibitory-control deficits compromise memory suppression in
posttraumatic stress disorder.
AB - Most people have experienced distressing events that they would rather forget.
Although memories of such events become less intrusive with time for the majority
of people, those with posttraumatic stress disorder (PTSD) are afflicted by
vivid, recurrent memories of their trauma. Often triggered by reminders in the
daily environment, these memories can cause severe distress and impairment. We
propose that difficulties with intrusive memories in PTSD arise in part from a
deficit in engaging inhibitory control to suppress episodic retrieval. We tested
this hypothesis by adapting the think/no-think paradigm to investigate voluntary
memory suppression of aversive scenes cued by naturalistic reminders. Retrieval
suppression was compromised significantly in PTSD patients, compared with trauma
exposed control participants. Furthermore, patients with the largest deficits in
suppression-induced forgetting were also those with the most severe PTSD
symptoms. These results raise the possibility that prefrontal mechanisms
supporting inhibitory control over memory are impaired in PTSD.
PMID- 25847538
TI - Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans
interaction.
PMID- 25847537
TI - Open source software for quantification of cell migration, protrusions, and
fluorescence intensities.
AB - Cell migration is frequently accompanied by changes in cell morphology
(morphodynamics) on a range of spatial and temporal scales. Despite recent
advances in imaging techniques, the application of unbiased computational image
analysis methods for morphodynamic quantification is rare. For example, manual
analysis using kymographs is still commonplace, often caused by lack of access to
user-friendly, automated tools. We now describe software designed for the
automated quantification of cell migration and morphodynamics. Implemented as a
plug-in for the open-source platform, ImageJ, ADAPT is capable of rapid,
automated analysis of migration and membrane protrusions, together with
associated fluorescently labeled proteins, across multiple cells. We demonstrate
the ability of the software by quantifying variations in cell population
migration rates on different extracellular matrices. We also show that ADAPT can
detect and morphologically profile filopodia. Finally, we have used ADAPT to
compile an unbiased description of a "typical" bleb formed at the plasma membrane
and quantify the effect of Arp2/3 complex inhibition on bleb retraction.
PMID- 25847539
TI - G3BP1 promotes stress-induced RNA granule interactions to preserve polyadenylated
mRNA.
AB - G3BP1, a target of TDP-43, is required for normal stress granule (SG) assembly,
but the functional consequences of failed SG assembly remain unknown. Here, using
both transformed cell lines and primary neurons, we investigated the functional
impact of this disruption in SG dynamics. While stress-induced translational
repression and recruitment of key SG proteins was undisturbed, depletion of G3BP1
or its upstream regulator TDP-43 disturbed normal interactions between SGs and
processing bodies (PBs). This was concomitant with decreased SG size, reduced SG
PB docking, and impaired preservation of polyadenylated mRNA. Reintroduction of
G3BP1 alone was sufficient to rescue all of these phenotypes, indicating that
G3BP1 is essential for normal SG-PB interactions and SG function.
PMID- 25847541
TI - Epilepsy surgery trends in the United States: Differences between children and
adults.
PMID- 25847540
TI - Phosphorylated ubiquitin chain is the genuine Parkin receptor.
AB - PINK1 selectively recruits Parkin to depolarized mitochondria for quarantine and
removal of damaged mitochondria via ubiquitylation. Dysfunction of this process
predisposes development of familial recessive Parkinson's disease. Although
various models for the recruitment process have been proposed, none of them
adequately explain the accumulated data, and thus the molecular basis for PINK1
recruitment of Parkin remains to be fully elucidated. In this study, we show that
a linear ubiquitin chain of phosphomimetic tetra-ubiquitin(S65D) recruits Parkin
to energized mitochondria in the absence of PINK1, whereas a wild-type tetra
ubiquitin chain does not. Under more physiologically relevant conditions, a
lysosomal phosphorylated polyubiquitin chain recruited phosphomimetic Parkin to
the lysosome. A cellular ubiquitin replacement system confirmed that ubiquitin
phosphorylation is indeed essential for Parkin translocation. Furthermore,
physical interactions between phosphomimetic Parkin and phosphorylated
polyubiquitin chain were detected by immunoprecipitation from cells and in vitro
reconstitution using recombinant proteins. We thus propose that the
phosphorylated ubiquitin chain functions as the genuine Parkin receptor for
recruitment to depolarized mitochondria.
PMID- 25847542
TI - A study on the thermal conversion of scheelite-type ABO4 into perovskite-type
AB(O,N)3.
AB - Phase-pure scheelite AMoO4 and AWO4 (A = Ba, Sr, Ca) were thermally treated under
an ammonia atmosphere at 400 to 900 degrees C. SrMoO4 and SrWO4 were shown to
convert into cubic perovskite SrMoO2N and SrWO1.5N1.5, at 700 degrees C and 900
degrees C respectively, and to form metastable intermediate phases (scheelite
SrMoO4-xNx and SrWO4-xNx), as revealed by X-ray diffraction (XRD), elemental
analysis and FTIR spectroscopy. High-temperature oxide melt solution calorimetry
reveals that the enthalpy of formation for SrM(O,N)3 (M = Mo, W) perovskites is
less negative than that of the corresponding scheelite oxides, though the
conversion of the scheelite oxides into perovskite oxynitrides is
thermodynamically favorable at moderate temperatures. The reaction of BaMO4 with
ammonia leads to the formation of rhombohedral Ba3M2(O,N)8 and the corresponding
binary metal nitrides Mo3N2 and W4.6N4; similar behavior was observed for CaMO4,
which converted upon ammonolysis into individual oxides and nitrides. Thus, BaMO4
and CaMO4 were shown to not provide access to perovskite oxynitrides. The
influence of the starting scheelite oxide precursor, the structure distortion and
the degree of covalency of the B-site-N bond are discussed within the context of
the formability of perovskite oxynitrides.
PMID- 25847543
TI - A radiographic study of estimating age by deciduous mandibular canine and molar
root resorption.
AB - BACKGROUND AND AIM: Root resorption of deciduous teeth is an important aspect of
dental development; however, the accuracy of using root resorption as a method of
estimating age has not been reported. The aim of this study was to assess the
accuracy of estimating age from fractions of resorbed root in mandibular
deciduous canines and molars, using published reference data. METHODS: The sample
was 940 dental panoramic radiographs of dental patients aged 3-16. Deciduous
mandibular canine and molar roots were staged into levels of resorption (one
quarter, one half and three quarters). Reliability of root fractions was assessed
using 193 duplicate readings and calculated using Kappa. Age was estimated using
Moorrees et al. (1963), Fanning (1961), and O'Meara and Knott (1967), and the
difference between dental and chronological ages tested using t-test. Accuracy
was defined as a difference not significant to zero (P<0.05). RESULTS: Results
show that assessment of levels of root resorption was excellent (Kappa 0.88
0.94). Some root fractions of molars estimated age accurately; however, the
standard deviation was more than 2 years. The average difference between dental
and chronological ages ranged from 0.12 to -2.04 years with standard deviation
values up to 2 years and the most accurate method was O'Meara and Knott (1967).
CONCLUSION: Fractions of deciduous root resorption can help to predict age.
PMID- 25847544
TI - Are qualitative and quantitative sleep problems associated with delinquency when
controlling for psychopathic features and parental supervision?
AB - The aim of this study was to explore the relationship between sleep, including
both qualitative and quantitative aspects, and delinquent behaviour while
controlling for psychopathic features of adolescents and parental supervision at
bedtime. We analysed data from a nationally representative sample of 4855 Finnish
adolescents (mean age 15.3 years, 51% females). Sleep problems, hours of sleep
and delinquency were evaluated via self-report. Psychopathic features were
measured with the Antisocial Process Screening Device - Self-Report. In negative
binomial regressions, gender and sleep-related variables acted as predictors for
both property and violent crime after controlling for psychopathic features and
parental supervision at bedtime. The results suggest that both sleep problems (at
least three times per week, at least for a year) and an insufficient amount of
sleep (less than 7 h) are associated with property crime and violent behaviour,
and the relationship is not explained by gender, degree of parental supervision
at bedtime or co-occurring psychopathic features. These results suggest that
sleep difficulties and insufficient amount of sleep are associated with
delinquent behaviour in adolescents. The significance of addressing sleep-related
problems, both qualitative and quantitative, among adolescents is thus
highlighted. Implications for a prevention technique of delinquent behaviour are
discussed.
PMID- 25847545
TI - The four or more medicines (FOMM) support service: results from an evaluation of
a new community pharmacy service aimed at over-65s.
AB - OBJECTIVE: Inappropriate prescribing and nonadherence have a significant impact
on hospital admissions and patient quality of life. The English government has
identified that community pharmacy could make a significant contribution to
reducing nonadherence and improving the quality of prescribing, reducing both
hospital admissions and medicines wastage. The objective of this study is to
evaluate a community pharmacy service aimed at patients over the age of 65 years
prescribed four or more medicines. METHODS: Patients were invited to participate
in the service by the community pharmacy team. The pharmacist held regular
consultations with the patient and discussed risk of falls, pain management,
adherence and general health. They also reviewed the patient's medication using
STOPP/START criteria. Data were analysed for the first 6 months of participation
in the service. KEY FINDINGS: Six hundred twenty patients were recruited with 441
(71.1%) completing the 6-month study period. Pharmacists made 142 recommendations
to prescribers in 110 patients largely centred on potentially inappropriate
prescribing of NSAIDs, PPIs or duplication of therapy. At follow-up, there was a
significant decrease in the total number of falls (mean -0.116 (-0.217--0.014))
experienced and a significant increase in medicine adherence (mean difference in
Morisky Measure of Adherence Scale-8: 0.513 (0.337-0.689)) and quality of life.
Cost per quality-adjusted life year estimates ranged from L11 885 to L32 466
depending on the assumptions made. CONCLUSION: By focussing on patients over the
age of 65 years with four or more medicines, community pharmacists can improve
medicine adherence and patient quality of life.
PMID- 25847547
TI - Functioning and quality of life in hoarding: A systematic review.
AB - Hoarding, the acquisition and inability to let go of a large number of
possessions, has been found to be associated with high levels of impairment that
can compromise functioning and quality of life (QoL). Yet few studies have
specifically investigated the relationship between hoarding and functioning/QoL.
The present review aimed to summarize the current status of research on
functioning and QoL in hoarding as well as identify knowledge gaps in the extant
literature. We conducted systematic searches in ProQuest, PsycINFO, PubMed and
ScienceDirect, and identified 37 relevant articles for inclusion. There was much
evidence to indicate that hoarding has a significant impact on various aspects of
functioning and that functioning can improve with treatment, though findings on
the relationship between hoarding and QoL were more tenuous. The limitations of
previous studies and implications of our findings are discussed.
PMID- 25847548
TI - Anxiety sensitivity and subjective social status in relation to anxiety and
depressive symptoms and disorders among Latinos in primary care.
AB - The present investigation examined the interactive effects of anxiety sensitivity
and subjective social status in relation to anxiety and depressive symptoms and
psychopathology among 143 Latinos (85.7% female; Mage=39.0, SD=10.9; 97.2% used
Spanish as their first language) who attended a community-based primary
healthcare clinic. Results indicated that the interaction between anxiety
sensitivity and subjective social status was significantly associated with number
of mood and anxiety disorders, panic, social anxiety, and depressive symptoms.
The form of the significant interactions indicated that individuals reporting co
occurring higher levels of anxiety sensitivity and lower levels of subjective
social status evidenced the greatest levels of psychopathology and panic, social
anxiety, and depressive symptoms. The present findings suggest that there is
merit in focusing further scientific attention on the interplay between anxiety
sensitivity and subjective social status in regard to understanding, and thus,
better intervening to reduce anxiety/depressive vulnerability among Latinos in
primary care.
PMID- 25847550
TI - Harvesting the benefits of clinical case reports: how to separate the chaff from
the wheat?
PMID- 25847549
TI - Does every transcript originate from a gene?
AB - Outdated gene definitions favored regions corresponding to mature messenger RNAs,
in particular, the open reading frame. In eukaryotes, the intergenic space was
widely regarded nonfunctional and devoid of RNA transcription. Original concepts
were based on the assumption that RNA expression was restricted to known protein
coding genes and a few so-called structural RNA genes, such as ribosomal RNAs or
transfer RNAs. With the discovery of introns and, more recently, sensitive
techniques for monitoring genome-wide transcription, this view had to be
substantially modified. Tiling microarrays and RNA deep sequencing revealed
myriads of transcripts, which cover almost entire genomes. The tremendous
complexity of non-protein-coding RNA transcription has to be integrated into
novel gene definitions. Despite an ever-growing list of functional RNAs,
questions concerning the mass of identified transcripts are under dispute. Here,
we examined genome-wide transcription from various angles, including evolutionary
considerations, and suggest, in analogy to novel alternative splice variants that
do not persist, that the vast majority of transcripts represent raw material for
potential, albeit rare, exaptation events.
PMID- 25847551
TI - Towards improving the reporting quality of clinical case reports in complementary
medicine: assessing and illustrating the need for guideline development.
AB - BACKGROUND: Case reports have had a varying level of recognition as a source of
evidence throughout the history of medicine. In recent years, there has been a
revival of interest in clinical case reports in both conventional and
complementary medicine. There is a need to further improve the reporting quality
of clinical case reports of different Complementary and Alternative Medicine
(CAM) therapies. OBJECTIVES: To provide an overview of the different objectives
for clinical case reports, identify those that are most relevant for CAM, and to
develop a conceptual framework for purpose orientated clinical case reporting
guidelines for CAM therapies. To practically illustrate the chosen approach by
developing a clinical case reporting guideline for homeopathic cases. METHODS:
The various objectives of clinical case reports were described by Prof. Milos
Jenicek, and the potential relevance of these objectives for CAM were discussed
and graded by a mixed panel of experts. A conceptual framework for developing
clinical case reporting guidelines for CAM treatments with specific objectives is
proposed. The aim is to integrate both 'generic' and 'CAM therapy specific'
quality items. This framework has been practically applied to the development of
a reporting guideline for clinical case reports in homoeopathy which will be
reported in a second article. RESULTS: An overview is given of the clinical case
reporting literature. The conceptual framework for the development of purpose
orientated CAM clinical case reporting guidelines is presented. This framework is
based on alignment with the recently published 'generic' CARE guideline for
reporting of clinical case reports, whilst addressing the CAM specific elements
at the same time. CONCLUSIONS: The scope and importance of clinical case
reporting guideline development in CAM is illustrated. A conceptual framework for
developing CAM specific clinical case reporting guidelines was established. It
has been implemented using homoeopathy as an illustration, and this will be
reported in a separate article. Further improvements in clinical case reporting
in CAM will greatly contribute to CAM research and education, as well as to
improved patient care.
PMID- 25847552
TI - Clinical effectiveness of osteopathic treatment in chronic migraine: 3-Armed
randomized controlled trial.
AB - OBJECTIVE: To assess the effectiveness of OMT on chronic migraineurs using HIT-6
questionnaire, drug consumption, days of migraine, pain intensity and functional
disability. DESIGN: 3-Armed randomized controlled trial setting: all patients
admitted in the Department of Neurology of Ancona's United Hospitals, Italy, with
a diagnosis of migraine and without chronic illness, were considered eligible for
the study. INTERVENTIONS: Patients were randomly divided into three groups: (1)
OMT+medication therapy, (2) sham+medication therapy and (3) medication therapy
only. Patients received 8 treatments in a study period of 6 months. MAIN OUTCOME
MEASURES: Changing from baseline HIT-6 score. RESULTS: 105 subjects were
included. At the end of the study, ANOVA showed that OMT significantly reduced
HIT-6 score (mean change scores OMT-conventional care: -8.74; 95% confidence
interval (CI) -12.96 to -4.52; p<0.001 and OMT-sham: -6.62; 95% CI -10.85 to
2.41; p<0.001), drug consumption (OMT-sham: RR=0.22, 95% CI 0.11-0.40; OMT
control: RR=0.20, 95% CI 0.10-0.36), days of migraine (OMT-conventional care: M=
21.06; 95% CI -23.19 to -18.92; p<0.001 and OMT-sham: -17.43; 95% CI -19.57 to
15.29; p<0.001), pain intensity (OMT-sham: RR=0.42, 95% CI 0.24-0.69; OMT
control: RR=0.31, 95% CI 0.19-0.49) and functional disability (p<0.001).
CONCLUSIONS: These findings suggest that OMT may be considered a valid procedure
for the management of migraineurs. The present trial was registered on
www.ClinicalTrials.gov (identifier: NCT01851148).
PMID- 25847553
TI - Evaluation of plant based formulation on adolescent obesity and its associated
bio-markers: a randomized, double blind, placebo controlled study.
AB - OBJECTIVE: Obesity and overweight are the fifth most fatal diseases leading to an
increased rate of morbidity and mortality in global population, with its
incidence increasing drastically. Taking this into consideration we have
conducted the present study in order to explore the efficacy of plant based
formulation in the management of adolescent obesity and its associated
biomarkers. DESIGN: Randomized, double blind, placebo controlled trial was
conducted in 130 obese adolescent of both sexes, with BMI above 25kg/m(2). The
subjects were randomly assigned into test formulation group (TFG) and placebo
group (PG). TFG received two 500mg capsule containing test formulation whereas,
the PG received two 500mg of cellulose powder containing capsule daily for 3
months. The parameters such as blood pressure, inflammatory cytokines, adipokines
and lipid profile were assessed in all subjects pre and post treatment. RESULTS:
There was a considerable improvement in the levels of lipid profile, inflammatory
cytokines, adipokines and blood pressure after treatment in TFG compared to PG.
The statistical difference obtained between the groups after three months of
treatment for the various biomarkers are given as mean with 95% CI for BMI (
1.4+/-0.6 (-2.5 to -0.7)), total cholesterol mg/dl (-20.9+/-5.0 (-30.8 to
11.0)), triglyceride mg/dl (-12.9+/-5.7 (-23.9 to -1.2)), HDL-c mg/dl (7.2+/-0.8
(5.6-8.8)), IL-6 (-0.7+/-0.1 (-0.9 to -0.6)), hs C-reactive protein (CRP) mg/l(
1.0+/-0.01 (-1.2 to -0.8)), adiponectin ug/ml(4.9+/-0.4 (4.2-5.7)), leptin ng/ml
(-8.0+/-1.4 (-10.7 to -5.3)), diastolic blood pressure (DBP) mmHg (-10.4+/-0.8 (
12.0 to -8.7)) and systolic blood pressure (SBP) mmHg (-6.7+/-0.7 (-8.1 to
5.3)). Also, there was a statistical significance within group TFG. CONCLUSION:
The study concludes that the test formulation may prevent the future cardio
vascular risk incidence in obese adolescents by reducing inflammation,
overweight, lipid profile and by regulating adipokines. Thus it may help to
improve the health pattern in obese patients with least side effects.
PMID- 25847554
TI - Clinical efficacy of the co-administration of Turmeric and Black seeds (Kalongi)
in metabolic syndrome - a double blind randomized controlled trial - TAK-MetS
trial.
AB - OBJECTIVE: To compare the clinical efficacy of Black seeds and Turmeric alone and
its co-administration in lower doses among patients with metabolic syndrome
(MetS). DESIGN: Double-blind-randomized-controlled trial. SETTING: Hijrat colony,
Karachi, Pakistan. INTERVENTION: Apparently healthy males (n=250), who screened
positive for MetS, were randomized to either Black seeds (1.5g/day), Turmeric
(2.4g/day), its combination (900mg Black seeds and 1.5g Turmeric/day) or placebo
for 8 weeks. MAIN OUTCOME MEASURES: body-mass-index (BMI), body-fat-percent
(BF%), waist-circumference (WC), hip-circumference (HC), blood pressure (BP),
lipid-profile (cholesterol, HDL-cholesterol, LDL-cholesterol and TG), fasting
blood glucose (FBG) and c-reactive protein (CRP). RESULTS: At 4 weeks, compared
to baseline, Black seed and Turmeric alone showed improvement in BMI, WC and BF%.
Combination improved all parameters except HDL-cholesterol with lower FBG and LDL
cholesterol as compared to placebo. At 8 weeks, compared to placebo, Black seeds
reduced lipids and FBG, while Turmeric reduced LDL-cholesterol and CRP.
Interestingly, combination group with 60% dose of the individual herbs showed an
improvement in all parameters from baseline. When compared to placebo, it reduced
BF%, FBG, cholesterol, TG, LDL-cholesterol, CRP and raised HDL-cholesterol.
CONCLUSION: Turmeric and Black seeds showed improvement in all parameters of
metabolic syndrome, when co-administered at 60% of doses of individual herbs with
enhanced efficacy and negligible adverse-effects. The combination of Black seeds
and Turmeric can therefore, be recommended with lifestyle modification as a
starting point for patients with MetS to halt its future complications and
progression.
PMID- 25847555
TI - Tango for treatment of motor and non-motor manifestations in Parkinson's disease:
a randomized control study.
AB - OBJECTIVE: To determine effects of Argentine tango on motor and non-motor
manifestations of Parkinson's disease. DESIGN: Randomized control trial.
PARTICIPANTS: Forty patients with idiopathic Parkinson's disease. SETTING:
Movement disorder clinic and dance studio. INTERVENTION: Two randomized groups:
group (N=18) with 24 partnered tango classes, and control self-directed exercise
group (N=15). MAIN OUTCOMES MEASURES: The primary outcome was overall motor
severity. Secondary outcomes included other motor measures, balance, cognition,
fatigue, apathy, depression and quality of life. RESULTS: On the primary
intention-to-treat analysis there was no difference in motor severity between
groups MDS-UPDRS-3 (1.6 vs.1.2-point reduction, p=0.85). Patient-rated clinical
global impression of change did not differ (p=0.33), however examiner rating
improved in favor of tango (p=0.02). Mini-BESTest improved in the tango group
compared to controls (0.7+/-2.2 vs. -2.7+/-5.9, p=0.032). Among individual items,
tango improved in both simple TUG time (-1.3+/-1.6s vs. 0.1+/-2.3, p=0.042) and
TUG Dual Task score (0.4+/-0.9 vs. -0.2+/-0.4, p=0.012), with borderline
improvement in walk with pivot turns (0.2+/-0.5 vs. -0.1+/-0.5, p=0.066). MoCa
(0.4+/-1.6 vs. -0.6+/-1.5, p=0.080) and FSS (-3.6+/-10.5 vs. 2.5+/-6.2, p=0.057)
showed a non-significant trend toward improvement in the tango group. Tango
participants found the activity more enjoyable (p<0.001) and felt more "overall"
treatment satisfaction (p<0.001). We found no significant differences in other
outcomes or adverse events. CONCLUSION: Argentine tango can improve balance, and
functional mobility, and may have modest benefits upon cognition and fatigue in
Parkinson's disease. These findings must be confirmed in longer-term trials
explicitly powered for cognition and fatigue.
PMID- 25847556
TI - Measuring expectations of benefit from treatment in acupuncture trials: a
systematic review.
AB - OBJECTIVES: We conducted a systematic review that aimed to document and describe
how (1) expectation of benefit from treatment (response expectancies) were
measured and reported in acupuncture trials, and (2) examine any effect on
outcomes. DESIGN: We searched MEDLINE, EMBASE, AMED, CIHAHL, CENTRAL and Science
and Technology Proceedings up to November 2007 for randomised (RCT) and quasi
randomised (CCT) controlled trials and prospective controlled cohorts of
acupuncture as treatment for a medical or psychological condition in adults. An
update citation search was conducted in April 2010. We included studies that
mentioned soliciting response expectancies. RESULTS: We found 58 RCTs that
fulfilled our inclusion criteria. Around half referenced one of five published
instruments, most of which were designed to measure sham credibility and included
one question on response expectancy. A wide range of question phrasing and
response scales was used. There was some evidence that response scales may
influence the measurement of expectations. Eight trials analysed the association
between pre-randomisation expectations for assigned treatment and outcomes, and
six the effect of pre-randomisation expectations across all patients independent
of treatment allocation. Some showed associations but others did not.
CONCLUSIONS: There is some evidence that response expectancies interact with
outcomes in acupuncture trials however the variety of question phrasing and
analysis methods precludes drawing a firm conclusion about for whom and under
which circumstance. To further our understanding of expectations, more
methodological work is needed to standardise the questions and response scales
that are used.
PMID- 25847557
TI - A randomized controlled trial of auricular acupressure in heart rate variability
and quality of life for hypertension.
AB - BACKGROUND: Hypertension is one of the most common chronic diseases. Hypertensive
patients who intend to control blood pressure need professional medical
assistance. Auricular acupressure is a patient-dependent task, wherein a person
does not have to rely on a healthcare professional to self-perform the task.
OBJECTIVE: To evaluate the effects of auricular acupressure on heart rate
variability (HRV) and quality of life (QoL) in patients with hypertension.
METHODS: A randomized controlled trial with permuted block randomization was
used. In total, 150 participants from a medical teaching hospital were randomly
assigned to the experimental group that received auricular acupressure for 10
weeks, and the control group that received only routine care of equal duration.
Outcomes were assessed through HRV parameters, heart rate, blood pressure, and
QoL before and after the auricular acupressure intervention. RESULTS: After the
adjustment of disease duration and mental health, a significant difference
existed between the two groups in body pain (p=.03) and mental health (p=.002) of
QoL, but not in HRV parameters, heart rate, blood pressure, and overall QoL
(p>.05). CONCLUSION: Acupressure can be applied at the acupoints of shenmen,
sympathesis, kidney, liver, heart, and subcortex to improve physical pain and
mental health of QoL for hypertensive patients. Auricular acupressure is
acceptable and feasible although it does not support physiological benefits.
Further studies are warranted to assure the effects of using auricular
acupressure as an adjunctive care for patients with hypertension.
PMID- 25847558
TI - Effects of dance on motor functions, cognitive functions, and mental symptoms of
Parkinson's disease: a quasi-randomized pilot trial.
AB - OBJECTIVE: To examine the effectiveness of dance on motor functions, cognitive
functions, and mental symptoms of Parkinson's disease (PD). DESIGN: This study
employed a quasi-randomised, between-group design. SETTING: Dance, PD exercise,
and all assessments were performed in community halls in different regions of
Japan. PARTICIPANTS: Forty-six mild-moderate PD patients participated.
INTERVENTION: Six PD patient associations that agreed to participate in the study
were randomly assigned to a dance group, PD exercise group, or non-intervention
group. The dance and PD exercise groups performed one 60-min session per week for
12 weeks. Control group patients continued with their normal lives. All groups
were assessed before and after the intervention. MAIN OUTCOME MEASURES: We used
the Timed Up-and-Go Test (TUG) and Berg Balance Scale (BBS) to assess motor
function, the Frontal Assessment Battery at bedside (FAB) and Mental Rotation
Task (MRT) to assess cognitive function, and the Apathy Scale (AS) and Self
rating Depression Scale (SDS) to assess mental symptoms of PD. The Unified
Parkinson's Disease Rating Scale (UPDRS) was used for general assessment of PD.
RESULTS: When comparing results before and after intervention, the dance group
showed a large effect in TUG time (ES=0.65, p=0.006), TUG step number (ES=0.66,
p=0.005), BBS (ES=0.75, p=0.001), FAB (ES=0.77, p=0.001), MRT response time
(ES=0.79, p<0.001), AS (ES=0.78, p<0.001), SDS (ES=0.66, p=0.006) and UPDRS
(ES=0.88, p<0.001). CONCLUSIONS: Dance was effective in improving motor function,
cognitive function, and mental symptoms in PD patients. General symptoms in PD
also improved. Dance is an effective method for rehabilitation in PD patients.
PMID- 25847559
TI - Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in
elderly patients with pre-existing cerebral ischemia.
AB - SPECIFIC AIM: Cerebral injury caused by hypoperfusion during the perioperative
period is one of the main causes of disability and death in patients after major
surgery. No effective protective or preventative strategies have been identified.
This study was designed to evaluate the effects of Ginkgo biloba extract on
cerebral oxygen and glucose metabolism in elderly patients with known, pre
existing cerebral ischemia. METHODS: Sixty ASA (American Society of
Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by
transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip
replacement surgery, were enrolled in the study. They were randomly allocated to
receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D
group n=30) after induction of anesthesia. Blood samples were collected from
radial artery and jugular venous bulb catheters for blood gas analysis and
determination of glucose and lactate concentrations preoperatively, before
surgical incision, at the end of surgery, and on post-op day 1. Arterial O2
content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content
difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous
glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated.
RESULTS: There were no significant differences in CaO2 or Da-jvGlu during surgery
between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal
jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at
the end of surgery (T2) and on post-op day 1 (T3) than those in the control group
(p<0.05). CONCLUSION: Ginkgo biloba extract can improve cerebral oxygen supply,
decrease cerebral oxygen extraction rate and consumption, and help maintain the
balance between cerebral oxygen supply and consumption. It has no effect,
however, on cerebral glucose metabolism in elderly patients with known, pre
existing cerebral ischemia.
PMID- 25847560
TI - Efficacy of adjuvant Chinese herbal formula treatment for chronic tinnitus: a
retrospective observational study.
AB - BACKGROUND: The aim of this study was to evaluate the clinical efficacy of using
western anti-tinnitus therapy with or without Chai-Hu-Jia-Long-Gu-Mu-Li-Tang
(CHJLGMLT) to treat patients with chronic tinnitus. METHODS: A descriptive case
series with chart review was established to compare patients with chronic
tinnitus who had received CHJLGMLT with western anti-tinnitus therapy (the
CHJLGMIT group) with those who received western anti-tinnitus therapy alone (the
non-CHJLGMIT group). We included 21 patients, 10 patients in the CHJLGMIT group
with CHJLGMLT and 11 patients in the non-CHJLGMIT group. Both groups were
comparable in terms of patient demographics and clinical characteristics. The
follow-up examinations included the assessment of Tinnitus Handicap Inventory
(THI), Pittsburgh Sleep Quality Index (PSQI), Visual Analogue Scale (VAS) of 0-10
for tinnitus intensity, pure tone audiometry (PTA), and speech reception
threshold (SRT). RESULTS: After 2 months of treatment, THI and PSQI scores were
reduced significantly more in the CHJLGMIT group (p<0.05) than in the non
CHJLGMIT group. Scores on the emotional subscale of the THI were significantly
reduced in the CHJLGMIT group (p<0.05) after treatment, but the effects on the
seven PSQI subscales did not differ significantly between the two groups
(p>0.05). Scores on the VAS for tinnitus loudness were significantly reduced in
both groups (p<0.05). No significant differences between the two groups were
found on the binaural hearing tests (PTA and SRT). CONCLUSIONS: Our study found
that adjuvant CHJLGMLT therapy for chronic tinnitus may exert additional efficacy
by improving psychological sensation of tinnitus and sleep quality. Future
randomized controlled double-blind studies should be performed to elucidate its
efficacy.
PMID- 25847561
TI - Effects of symptoms and complementary and alternative medicine use on the yang
deficiency pattern among breast cancer patients receiving chemotherapy.
AB - BACKGROUND: Based on traditional Chinese medicine (TCM) theory, yang deficiency
pattern defined as an insufficiency of meridian energy (qi) is related to
worsening disease symptoms. However, there is a lack of studies portraying the
relationship among complementary and alternative medicine (CAM) use, symptoms,
and meridian energy. Therefore, the primary purpose of this study was to describe
the changes of CAM use, symptoms, and yang deficiency pattern among patients with
breast cancer receiving chemotherapy. Additionally, the study explored factors
predicting yang deficiency pattern. METHOD: A longitudinal study was performed
with 153 women with breast cancer at four teaching hospitals in northern Taiwan
from June 1, 2009 to July 31, 2013. Researchers collected data before treatment
and the 1st and 3rd months after chemotherapy. Yang deficiency pattern was
examined using the Meridian Energy Analysis Device Me-Pro. Symptom severity and
interference were assessed using the MD Anderson Symptom Inventory-Taiwan
version. CAM use was evaluated using the US National Center for Complementary and
Alternative Medicine (NCCAM) classification. RESULTS: Meridian energy remained
essentially the same over the 3-month period as the difference was not
statistically significant. As time went by, patients developed worsening symptom
severity and interference. More than 66% of the patients used CAM during
chemotherapy. Older women had lower overall meridian energy. The more severe the
symptoms were, the lower the overall meridian energy was. The patients who used
tai chi or qi gong had higher overall meridian energy and those who used prayer
or spirituality had lower overall meridian energy. CONCLUSION AND IMPLICATIONS:
Symptom severity and interference among patients deteriorated during
chemotherapy. Health providers should observe symptom changes and improve yang
deficiency pattern. Whether or not use of CAM practices such as tai chi or qi
gong improves the overall health of breast cancer patients on chemotherapy is
worth further study.
PMID- 25847562
TI - Communication of professional literature amongst European Acupuncturists
affiliated to the ETCMA (European Traditional Chinese Medicine Association):
explorative survey amongst Traditional Chinese Medicine practitioners in Europe.
AB - OBJECTIVES: The primary aim of the survey was to explore the information needs
and information seeking behavior amongst the ETCMA members concerning
professional literature (scientific as well as practical background knowledge).
METHODS: A web-based survey comprising of 18 questions with a total of 25 items
was carried out in 15 affiliated associations in 14 countries in June 2012. The
survey consisted out of 4 parts: (1) Demographics, (2) Level of interest in and
availability of professional literature, (3) Insight, needs and opinions on EBM
(Evidence Based Medicine), and (4) Awareness of the science workshop at the TCM
Rothenburg Congress. RESULTS: 2590 (25%) from 10,428 members completed the
questionnaire, of which 58.8% was female. More than 50% of the respondents from
eleven out of fourteen countries indicate an interest in more education on
reading scientific literature. Case studies (range 3.19/4-3.86/4) are preferred
compared to scientific (range 2.78/4-3.59/4) or philosophical knowledge (range
3.0/4-3.56/4). Exchange with colleagues (range 2.95/4-3.64/4) is preferred
compared to deepening knowledge (range 2.57/4-3.05/4) in the theoretical
spectrum. 61% has no knowledge of the EBM model and base clinical decisions on
personal experience (range 3.47-3.82) and practical skills (range 3.47-3.74)
compared to clinical practice guidelines (range 2.6-3.27). CONCLUSIONS: Due to
heterogeneity in structure and size of the affiliated associations no strict
conclusions can be made. We can conclude though that TCM practitioners rely
mostly on practical knowledge and have less tendency toward more scientifically
oriented models like the EBM model. We find this reflected in information needs
as well as information seeking behavior patterns.
PMID- 25847563
TI - A case of chemotherapy-induced congestive heart failure successfully treated with
Chinese herbal medicine.
AB - OBJECTIVE: A case is presented to illustrate a potential effect of Chinese herbal
medicine (CHM) formulas in treating chemotherapy-induced cardiotoxicity. CLINICAL
PRESENTATION: An 18-year-old adolescent male with refractory acute lymphoblastic
leukemia (ALL) had experienced anthracycline-induced congestive heart failure
(CHF) for 3 weeks. Under intensive care with conventional therapy, the patient
still had exercise intolerance and depended on supplemental oxygen all day.
Therefore, he consented to treatment with traditional Chinese medicine (TCM) for
alternative therapy. INTERVENTIONS AND OUTCOMES: This patient was treated with
modified Zhi Gan Cao Tang (ZGCT), three times a day for 2 months. After 6 days of
CHM treatment, the patient could tolerate daily activity without supplemental
oxygen. After 2 months of CHM treatment, the follow-up chest X-ray showed great
improvements in pulmonary edema and cardiomegaly. CONCLUSIONS: In this case,
anthracycline-induced cardiotoxicity resolved slowly following the administration
of modified ZGCT. It is suggested that the CHM formula has a protective effect on
the progression of CHF secondary to the use of anthracyclines in pediatric
cancer. Further studies to determine the mechanism and clinical trials are
warranted.
PMID- 25847564
TI - Student identification of the need for complementary medicine education in
Australian medical curricula: a constructivist grounded theory approach.
AB - OBJECTIVE: Across the Western world, including Australia, growing popularity of
complementary medicines (CMs) mandates their implementation into medical
education (ME). Medical students in international contexts have expressed a need
to learn about CMs. In Australia, little is known about the student-specific need
for CM education. The objective of this paper was to assess the self-reported
need for CM education among Australian medical students. DESIGN: Thirty second
year to final-year medical students participated in semi-structured interviews. A
constructivist grounded theory methodological approach was used to generate,
construct and analyse data. SETTING: Medical school education faculties in
Australian universities. RESULTS: Medical students generally held favourable
attitudes toward CMs but had knowledge deficits and did not feel adept at
counselling patients about CMs. All students were supportive of CM education in
ME, noting its importance in relation to the doctor-patient encounter,
specifically with regard to interactions with medical management. As future
practitioners, students recognised the need to be able to effectively communicate
about CMs and advise patients regarding safe and effective CM use. CONCLUSIONS:
Australian medical students expressed interest in, and the need for, CM education
in ME regardless of their opinion of it, and were supportive of evidence-based
CMs being part of their armamentarium. However, current levels of CM education in
medical schools do not adequately enable this. This level of receptivity suggests
the need for CM education with firm recommendations and competencies to assist CM
education development required. Identifying this need may help medical educators
to respond more effectively.
PMID- 25847565
TI - Traditional herbal medicine for cancer pain: a systematic review and meta
analysis.
AB - BACKGROUND: The effectiveness of traditional herbal medicine (THM) as an
adjunctive therapy for cancer pain is unclear. OBJECTIVE: To assess the
effectiveness of THM as an adjunctive therapy for cancer pain using randomized
controlled trials (RCTs). METHODS: Five electronic databases, including those
from the UK and China, were systematically searched for the period before
September 2013. All RCTs involving the use of THM in combination with
conventional cancer therapy for cancer pain were included. RESULTS: Twenty-four
RCTs involving 4889 patients with cancer pain were systematically reviewed. Among
them, nine studies of 952 patients reported a significant decrease in the number
of patients with cancer pain in the treatment group. Four studies of 1696
patients reported a significant decrease in the degree of pain in the treatment
group. CONCLUSION: The results of these studies suggest that THM combined with
conventional therapy is efficacious as an adjunctive therapy for patients with
cancer pain. However, more research, including well-designed, rigorous, and
larger clinical trials, are necessary to address these issues.
PMID- 25847566
TI - Effects of black seed (Nigella sativa) on metabolic parameters in diabetes
mellitus: a systematic review.
AB - BACKGROUND: Current evidence indicated beneficial effects of some medicinal herbs
on metabolic parameters. Nigella sativa is an example of herbs which can
ameliorate metabolic factors in diabetes mellitus. Despite several narrative
review studies on medicinal properties of NS, it seems that there is no
systematic review to summarize effects of NS on glucose homoeostasis and lipid
profile in diabetes mellitus. Therefore, the aim of present study was to review
effects of N. sativa on metabolic parameters in diabetes mellitus. METHODS:
Pubmed, Science Direct, Google scholar and Springer databases were searched from
1995 till January 2014. Key words were included: N. sativa, black seed, diabetes,
glucose level, lipid and insulin. Searching was limited to articles with English
language. Review articles, case reports, abstract in symposium and congress,
studies on N. sativa mixed with other plants were excluded. Based on critically
appraise, eligibility of included articles were evaluated. RESULTS: Finally 19
eligible articles (2 human trials, 14 animal models and 3 in vivo/in vitro
studies) were selected. They indicated that N. sativa can modulate hyperglycemia
and lipid profile dysfunction with various potential mechanisms including its
antioxidant characteristics and effects on insulin secretion, glucose absorption,
gluconeogenesis and gene expression. Some studies compared effects of various
types (extract, oil, powdered) of N. sativa with each other and they reported
different characteristics with various types of black seed. CONCLUSION: N. sativa
can improve glycemic status and lipid profile in diabetes models. However, more
clinical trials are necessary to clarify beneficial effects of N. sativa, its
effective type and dosage for diabetes management and its complications.
PMID- 25847567
TI - Oral Chinese herbal medicine for kidney nourishment in Alzheimer's disease: a
systematic review of the effect on MMSE index measures and safety.
AB - OBJECTIVE: To evaluate the effectiveness and safety of the Chinese herbal
medicine for kidney nourishment (CHMK) assessed with the Mini-Mental Status
Examination (MMSE) index objective outcome measures in individuals with
Alzheimer's disease. METHODS: Searches were conducted in 7 medical databases from
their inceptions until July 19, 2014 for randomized controlled trials (RCTs) that
compared the oral administration of CHMK plus conventional pharmacotherapy with
the same conventional pharmacotherapy alone with MMSE index measures as outcomes.
Relevant resources were also manually retrieved. Two reviewers screened the
citations of the reports, assessed the risk of bias and extracted data
independently. Data analysis was carried out with Cochrane Collaboration's
RevMan5.2.6 software and evidence quality grading evaluation of the systematic
review was conducted with Grades of Recommendations Assessment Development and
Evaluation (GRADE) profiler software. RESULTS: A total of 20 studies involving
1682 participants were included in the meta-analysis. There were 15 trials that
compared CHMK with conventional pharmacotherapy and 5 trials that compared CHMK
plus conventional pharmacotherapy with conventional pharmacotherapy alone. The
main meta-analysis results showed relative benefits in effective rates in five
studies (odds ratio [OR] 2.74, 95% confidence interval [CI] 1.55-4.85) and cure
rate/clinical-control rates in five studies (OR 1.91, 95% CI 1.27-2.88) in favor
of the CHMK plus conventional pharmacotherapy group. As for CHMK compared with
conventional pharmacotherapy, no significant differences were noted in the
effective rate (OR 1.09, 95% CI 0.82-1.46; cure rate (OR 1.06, 95% CI 0.81-1.38)
and detailed sub-group of MMSE scores from the onset time to 4 weeks (weighted
mean difference [WMD] 0.31, 95% confidence interval [CI] -0.81 to 1.42, 8 weeks
WMD 1.12, 95% CI -0.54 to 2.78, 12 weeks (WMD 0.43, 95% CI -1.62 to 2.48, or 24
weeks WMD 1.92, 95% CI -1.60 to 5.44) follow-up and the overall effect (WMD 0.79,
95% CI -0.11 to 1.69). Moreover, weaknesses in methodological quality were
identified in most studies according to Cochrane Risk of Bias tool assessment,
while the quality level of GRADE classification indicated "very low". The
incidence of adverse events with CHMK (0.87%) was lower than in the conventional
pharmacotherapy group (4.08%), which revealed use of CHMK was relatively safer
than conventional pharmacotherapy alone. CONCLUSION: The effectiveness and safety
of oral administration of CHMK cannot be currently determined because of
publication bias and the low quality level of the included trials. Further
studies on a larger scale and with more rigorous designs are required to define
the role of CHMK in the treatment of AD.
PMID- 25847568
TI - Wen Dan Decoction for hemorrhagic stroke and ischemic stroke.
AB - OBJECTIVE: The use of traditional Chinese medicine (TCM) in stroke is increasing
worldwide. Here we report the existing clinical evidence of the Pinellia Ternata
containing formula Wen Dan Decoction (WDD) for the treatment of ischemic stroke
and hemorrhagic stroke. METHODS: PubMed, CNKI, Wan Fang database, Cochrane
Library and online Clinical Trial Registry were searched up to 26 February 2013
for randomized, controlled clinical trials (RCTs) using WDD as intervention
versus Western conventional medicine as control to treat stroke. Clinical
outcomes were improvement of the Neurological Functional Deficit Scores (NFDS)
and overall therapeutic efficacy rates including rate of cure. Meta-regression
analysis using Hedges'g was performed for RCTs with significant heterogeneity.
RESULTS: A total of 22 RCTs of ischemic stroke and 4 RCTs of hemorrhagic stroke,
involving 2214 patients (1167 used WDD), met our inclusion criteria. Meta
analysis of the 13 RCTs reporting NFDS improvement favored WDD over the control
(mean difference=-3.40, 95% confidence intervals [CI]=[-4.64, -2.15]). Rate of
overall therapeutic efficacy (odds ratio [OR]=3.39, 95%CI=[1.81, 6.37]) for
hemorrhagic stroke were significantly higher in WDD treated patients than the
control subjects. In the 1898 patients with ischemic stroke, WDD medication also
achieved higher rates of cure (OR=2.22, 95%CI=[1.66, 2.97]) and overall
therapeutic efficacy (OR=3.31, 95%CI=[2.54, 4.31]) than the conventional
treatment. CONCLUSIONS: WDD displays benefits on improvement of neurological
function and overall therapeutic efficacy in post-stroke patients. TCM such as
WDD may serve as a therapeutic tool of dual actions to explore the common
mechanisms underlying cerebral hemorrhage and ischemia.
PMID- 25847569
TI - 'Suspended in a paradox'-patient attitudes to wait-listing for kidney
transplantation: systematic review and thematic synthesis of qualitative studies.
AB - Patients on waiting lists for kidney transplantation have higher mortality rates
and have specific anxieties about their eligibility, process, and outcomes of
wait-listing. We aimed to describe patient experiences and attitudes to wait
listing for kidney transplantation. Electronic databases were searched to
September 2014. Thematic synthesis was used to analyze the findings. From 22
studies (n = 795 patients), we identified six themes: accepting the only option
(chance to regain normality, avoiding guilt, impulsive decision-making);
maintaining hope (determined optimism, appreciating a fortuitous gift, enduring
for optimal outcomes, trust in clinical judgment); burden of testing (strenuous
commitment, losing the battle, medical mistrust); permeating vulnerability
(eligibility enigma, being threatened, angst of timing uncertainty, desperate
urgency, living in limbo, spiraling doubt and disappointment, residual
ambivalence); deprived of opportunity (unfairly dismissed, unexpected
disqualification, self-resignation and acceptance, jealousy, suspicious of
inequity); and moral guilt (awaiting someone's death, questioning deservingness).
The waiting list offered hope of restored normality. However, the demands of
workup, uncertainty about eligibility, and waiting times that exceeded
expectations impelled patients to disillusionment, despair, and suspicion of
inequity. Managing patient expectations and ensuring transparency of wait-listing
and allocation decisions may allay patient disappointment and skepticism, to
improve patient satisfaction and treatment outcomes.
PMID- 25847570
TI - Significance of decreased serum interleukin-10 levels in the progression of
cerebral infarction.
AB - Anti-inflammatory cytokine and its serological detection may have an important
role in the process of cardiovascular and cerebrovascular diseases. We
investigated whether serum interleukin-10 (IL-10) is associated with cerebral
infarction or not in the general population. Identified comprehensive searching
was performed covering PubMed, EMBASE, Web of Science, Cochrane Library, CISCOM,
CINAHL, Google Scholar, China BioMedicine, and China National Knowledge
Infrastructure databases. Two reviewers extracted data and assessed studies
independently. Information was extracted separately and classed into Asians and
Caucasians. Summary standardized mean differences (SMDs) with 95 % confidence
intervals (CI) were used with the utilization of Z test. Nine studies ranged from
2003 to 2014 were collected for meta-analysis. Results identified a negative
association between serum IL-10 levels and cerebral infarction (SMD = 1.80, 95 %
CI 0.79-2.81, P < 0.001). Country-subgroup analysis showed that low IL-10 level
may be the main risk factor for cerebral infarction in India (SMD = 1.44, 95 % CI
1.13-1.75, P < 0.001) and Croatia (SMD = 2.96, 95 % CI 2.48-3.44, P < 0.001). In
the ethnicity-stratified subgroup analysis, serum IL-10 levels were negatively
correlated with cerebral infarction in Asians (SMD = 2.52, 95 % CI 0.47-4.57, P =
0.016), while not in Caucasians (P > 0.05). The lower serum IL-10 concentration
was significantly associated with an increased likelihood of cerebral infarction
in this meta-analysis. More prospective studies should be conducted to provide
stronger evidence justifying the use of IL-10 as new biomarker to identify a
predisposition toward cerebral infarction.
PMID- 25847571
TI - Angiotensins as therapeutic targets beyond heart disease.
AB - The renin-angiotensin system (RAS) plays a pivotal role in cardiovascular and
hydro-electrolyte homeostasis. Blockade of the RAS as a therapeutic strategy for
treating hypertension and related cardiovascular diseases is well established.
However, actions of the RAS go far beyond the targets initially described. In
this regard, the recent identification of novel components of the RAS, including
angiotensin-(1-7) [Ang-(1-7)], Ang-(1-9), and alamandine, have opened new
possibilities for interfering with the development and manifestations of
cardiovascular and non-cardiovascular diseases. In this article, we briefly
review novel targets for angiotensins and its therapeutic implications in diverse
areas, including cancer, inflammation, and glaucoma.
PMID- 25847572
TI - Cost-effectiveness of sofosbuvir for the treatment of chronic hepatitis C
infected patients.
AB - The efficacy of treatment for hepatitis C genotype 1 infection has significantly
improved with the introduction of first-generation protease inhibitors. However,
there remains a need for effective treatments for patients infected with other
genotypes, for nonresponders and patients unsuitable for interferon. Sofosbuvir
is the first nucleotide polymerase inhibitor with pan-genotypic activity.
Sofosbuvir-based regimens have resulted in >90% sustained virological response
across treatment-naive genotype 1-6 patients in five phase III clinical trials of
sofosbuvir administered with ribavirin or pegylated interferon and ribavirin.
This analysis evaluates the cost-effectiveness of sofosbuvir within the current
licensed indication, for genotype 1-6 in the UK. A Markov model followed a cohort
of 10 000 patients over lifetime, with approximately 20% initiating treatment for
compensated cirrhosis. Sofosbuvir-regimens were compared to telaprevir,
boceprevir, pegylated interferon and ribavirin, or no treatment. Costs and
outcomes were discounted at 3.5%. The cost perspective utilized costs applicable
to the National Health Service in the UK. Sofosbuvir proved to be cost-effective
in most patient populations with incremental cost-effectiveness ratios (ICERs) at
L11 836/QALY and L7292/QALY against telaprevir and boceprevir, respectively. In
genotype 3, sofosbuvir had a weighted ICER of L18 761/QALY. Sofosbuvir-based
regimens are a cost-effective option for the majority of hepatitis C-infected
patients in the United Kingdom although the incremental cost-effectiveness varies
by genotype and regimen. Sofosbuvir and ribavirin is an alternative regimen for
patients unsuitable for interferon.
PMID- 25847573
TI - Interactions of Pt-ttpy with G-Quadruplexes Originating from Promoter Region of
the c-myc Gene Deciphered by NMR and Gel Electrophoresis Analysis.
AB - This study provides insights into the interactions of Pt-ttpy, that is, a metallo
organic heterocycle-comprising platinum(II) complex of terpyridine, and G
quadruplexes adopted by G-rich DNA from the transcriptional regulatory element of
the c-myc gene, a well-known attractive target for artificial modulation of
oncogene expression. A previously noted drug-like potential of Pt-ttpy relies on
its antiproliferative activity on cancer cells and its increased selectivity for
G-quadruplex binding attributed to the combination of distinct interacting modes.
The predominant interaction between the herein used models of a parallel G
quadruplex exhibiting short propeller-type loops and Pt-ttpy occurs through
stacking to the outer G-quartets. The presence of adenine versus thymine residue
at the 5'-end overhanging region allows the coordinative binding of Pt-ttpy to
the G-quadruplex structure. Interestingly, Pt-ttpy triggers the formation of the
G-quadruplex even in the absence of cations. Furthermore, NMR-based
characterisation revealed common structural features of Pt-ttpy-G-quadruplex
complexes in the presence and absence of cations, which indicate that cations may
be expelled from the cores of the corresponding structures.
PMID- 25847574
TI - Idiopathic Facial Aseptic Granuloma: Review of an Evolving Clinical Entity.
AB - Idiopathic facial aseptic granuloma (IFAG), originally termed pyodermite froide
du visage, describes a generally asymptomatic facial nodule presenting in
childhood with clinical resemblance to pyoderma or cystic, granulomatous, or
vascular lesions. Clinical understanding is constantly evolving, with recent
observations indicating that IFAG may represent a subtype of childhood rosacea.
We present a case of IFAG associated with eyelid chalazions in a 19-month-old
boy. Although his clinical course paralleled previously reported IFAG cases, we
observed a unique ultrasound variation during initial diagnostic examination.
Further delineation of clinical, imaging, and histologic properties of IFAG may
reveal insights into etiologic associations and ideal management.
PMID- 25847575
TI - Mutations in ANO3 and GNAL gene in thirty-three isolated dystonia families.
PMID- 25847576
TI - Effects and mechanism of ultrasound pretreatment on rapeseed protein enzymolysis.
AB - BACKGROUND: The disadvantages which stem from the use of traditional enzymolysis
of protein has necessitated the need to employ sweeping frequency and pulsed
ultrasound (SFPU) in the pretreatment of rapeseed protein prior to proteolysis in
order to bring about improvement in enzymolysis efficiency. Further, in order to
determine the mechanism of ultrasound-accelerated enzymolysis of RP, the effects
of SFPU on the kinetics, thermodynamics, molecular conformation and
microstructure of RP were investigated. RESULTS: Kinetic studies showed that SFPU
pretreatment on RP improved enzymolysis by decreasing the apparent constant KM
significantly (P < 0.05) by 32.8% and reducing the thermodynamic parameters Ea ,
DeltaH and DeltaS by 16.6%, 17.7% and 9.2% respectively. Fluorescence spectra
revealed that SFPU pretreatment induced molecular unfolding, causing more
hydrophobic groups and regions inside the molecules to be exposed to the outside.
Circular dichroism analysis indicated that SFPU pretreatment decreased the alpha
helix content by 16.1% and increased the random coil content by 3.6%. In
addition, scanning electron microscopy showed that SFPU pretreatment increased
the specific surface area of RP. CONCLUSION: Ultrasound pretreatment is an
efficient method in RP proteolysis to produce peptides through its impact on the
molecular conformation and microstructure of proteins.
PMID- 25847577
TI - Retaining traditionally hard to reach participants: Lessons learned from three
childhood obesity studies.
AB - Retaining underserved populations, particularly low-income and/or minority
participants in research trials, presents a unique set of challenges. In this
paper, we describe the initial retention strategies and enhanced the retention
strategies over time across three childhood obesity prevention trials. Hip-Hop to
Health Jr. (HH) was a randomized controlled trial (RCT) testing a preschool-based
obesity prevention intervention among predominately African-American children.
Retention was 89% at 14-weeks, 71% at 1-year, and 73% at 2-year follow-up.
Primary retention strategies for HH included: 1) collaboration with a community
based organization to enhance program credibility; 2) continuity of data
collection locations; 3) collecting detailed contact information and provision of
monetary compensation; and 4) developing a detailed tracking/search protocol. In
a follow-up trial, Hip-Hop to Health Jr. Obesity Prevention Effectiveness Trial
(HH Effectiveness), 95% of participants completed assessment at 14 weeks and 88%
completed assessment at 1 year. For this trial, we emphasized staffing continuity
in order to enhance participant relationship building and required data
collection staff to have relevant community service experience. In a third study,
we assessed dietary quality among participants in the Special Supplemental
Nutrition Program for Women, Infants, and Children (WIC) across three time points
following the WIC food package shift instituted nationally in 2009. Retention
rates were 91% at 12 months and 89% at 18 months. For our WIC? study, we
augmented retention by developing a home data collection protocol and increased
focus on staff diversity training. We conclude with a summary of key strategies
and suggestions for future research.
PMID- 25847578
TI - Telephone-adapted mindfulness-based stress reduction (tMBSR) for patients
awaiting kidney transplantation: Trial design, rationale and feasibility.
AB - BACKGROUND: Mindfulness-based stress reduction (MBSR) has demonstrated benefits
for stress-related symptoms; however, for patients with burdensome treatment
regimens, multiple co-morbidities and mobility impairment, time and travel
requirements pose barriers to MBSR training. PURPOSE: To describe the design,
rationale and feasibility results of Journeys to Wellness, a clinical trial of
mindfulness training delivered in a novel workshop and teleconference format. The
trial aim is to reduce symptoms and improve quality of life in people waiting for
a kidney transplant. METHODS: The standard 8-week MBSR program was reconfigured
for delivery as two in-person workshops separated in time by six weekly
teleconferences (tMBSR). A time and attention comparison condition (tSupport) was
created using the workshop-telephone format. FEASIBILITY RESULTS: Kidney
transplant candidates (N = 63) were randomly assigned to tMBSR or tSupport: 87%
(n = 55) attended >= 1 class, and for these, attendance was high (6.6 +/- 1.8
tMBSR and 7.0 +/- 1.4 tSupport sessions). Fidelity monitoring found that all
treatment elements were delivered as planned and few technical problems occurred.
Patients in both groups reported high treatment satisfaction, but more tMBSR
(83%) than tSupport (43%) participants expected their intervention to be quite a
bit or extremely useful for managing their health. Symptoms and quality of life
outcomes collected before (baseline, 8 weeks and 6 months) and after kidney
transplantation (2, 6 and 12 months) will be analyzed for efficacy. CONCLUSIONS:
tMBSR is an accessible intervention that may be useful to people with a wide
spectrum of health conditions. Clinicaltrials.gov: NCT01254214.
PMID- 25847579
TI - Use of mobile devices and the internet for multimedia informed consent delivery
and data entry in a pediatric asthma trial: Study design and rationale.
AB - INTRODUCTION: Phase III/IV clinical trials are expensive and time consuming and
often suffer from poor enrollment and retention rates. Pediatric trials are
particularly difficult because scheduling around the parent, participant and
potentially other sibling schedules can be burdensome. We are evaluating using
the internet and mobile devices to conduct the consent process and study visits
in a streamlined pediatric asthma trial. Our hypothesis is that these study
processes will be non-inferior and will be less expensive compared to a
traditional pediatric asthma trial. MATERIALS/METHODS: Parents and participants,
aged 12 through 17 years, complete the informed consent process by viewing a
multi-media website containing a consent video and study material in the
streamlined trial. Participants are provided an iPad with WiFi and EasyOne
spirometer for use during FaceTime visits and online twice daily symptom
reporting during an 8-week run-in followed by a 12-week study period. Outcomes
are compared with participants completing a similarly designed traditional trial
comparing the same treatments within the same pediatric health-system. After 8
weeks of open-label Advair 250/50 twice daily, participants in both trial types
are randomized to Advair 250/50, Flovent 250, or Advair 100/50 given 1 inhalation
twice daily. Study staff track time spent to determine study costs. RESULTS:
Participants have been enrolled in the streamlined and traditional trials and
recruitment is ongoing. CONCLUSIONS: This project will provide important
information on both clinical and economic outcomes for a novel method of
conducting clinical trials. The results will be broadly applicable to trials of
other diseases.
PMID- 25847580
TI - Helicobacter pylori with the Intact dupA Cluster is more Virulent than the
Strains with the Incomplete dupA Cluster.
AB - The duodenal ulcer promoting gene (dupA), located in the plasticity region of
Helicobacter pylori (H. pylori), is predicted to form a type IV secretory system
(T4SS) with vir genes around dupA. In the study, we investigated the association
between the dupA cluster status and the virulence of H. pylori in a littoral
region of Northeast China. Two hundred and sixty-two H. pylori strains isolated
from the chronic gastritis were examined to evaluate the dupA cluster status, cag
PAI genes and vacA genotype using PCR and Western blot. Histopathologic
evaluations of biopsy specimens were performed to analysis the association
between the dupA cluster and the inflammatory response. IL-8 productions in
gastric mucosa and from GES-1 cells co-cultured with H. pylori were measured,
respectively, to analysis the association between the dupA cluster status and IL
8 production. We found that gastric mucosal inflammatory cell infiltration was
significantly higher in patients with dupA-positive H. pylori, including H.
pylori with complete dupA cluster (2.71 +/- 0.79) and incomplete dupA cluster
(2.09 +/- 0.61) than in patients with dupA-negative strain (1.73 +/- 0.60, p <
0.01), whereas no significant difference in the gastric mucosal atrophy was found
according to the status of dupA cluster. Gastric mucosal IL-8 levels were higher
in the complete dupA cluster group than in other groups (p < 0.01), and IL-8
production from GES-1 cells was also significantly higher in strains with a
complete dupA cluster (1527.9 +/- 180.0 pg/ml) than in those with an incomplete
dupA cluster (1229.4 +/- 75.3 pg/ml, p < 0.01) or those with dupA negative
(1201.9 +/- 92.3 pg/ml, p < 0.01). In conclusion, the complete dupA cluster in H.
pylori is associated with inflammatory cell infiltration and IL-8 secretion, and
H. pylori strain with a complete dupA cluster seems to be more virulent than
other strains with the incomplete dupA cluster or dupA negative.
PMID- 25847582
TI - Seduced by technology?
PMID- 25847581
TI - ELP2 is a novel gene implicated in neurodevelopmental disabilities.
AB - Elongator is a multi-subunit protein complex essential to transcription
elongation, histone acetylation, and tRNA modification. The complex consists of
six highly conserved protein subunits, called Elongator Proteins (ELP) 1-6. Apart
from an association with intellectual disability (ID), there is limited clinical
information about patients with ELP2 variants. Here we report on two brothers
with severe ID, spastic diplegia, and self-injury whose presentation eluded a
diagnosis for over 20 years. In both brothers, whole exome sequencing revealed a
likely pathogenic, compound heterozygous missense variant in ELP2. We describe
the phenotype and natural history of the ELP2-related disorder in these brothers.
PMID- 25847584
TI - Nitroxide-Mediated Polymerization of Methacrylic Esters: Insights and Solutions
to a Long-Standing Problem.
AB - Nitroxide-mediated polymerization (NMP) is one of the most powerful reversible
deactivation radical polymerization techniques and has incredibly gained in
maturity and robustness over the last decades. However, control of methacrylic
esters is one of the different aspects of NMP that still requires improvement.
This family of monomers always represented an important challenge for NMP,
despite the many different nitroxide structures that have been designed over the
course of time. This Review aims to present the most successful strategies
directed toward the control of the NMP technique of methacrylic esters and
especially methyl methacrylate. NMP-derived materials comprising uncontrolled
methacrylate segments will also be discussed.
PMID- 25847583
TI - Isolation, identification, and characterization of the nematophagous fungus
Monacrosporium salinum from China.
AB - Nematophagous fungi are considered to have the best potential as biological
agents for the control of gastrointestinal nematodes in domestic animals.
However, relatively few studies have been conducted with the genus
Monacrosporium, especially with strains native to China. In the present study, we
isolated and identified nematophagous fungi from fresh sheep feces. A pure fungal
strain was molecularly characterized, and its nematophagous activity was
evaluated. The morphological plasticity of the isolated strain, as well as its
interaction with the nematode targets, was observed by scanning electron
microscopy of the infected Trichostrongylus colubriformis L3 and the free-living
nematode Caenorhabditis elegans. Three isolated fungal strains from the 30 fresh
fecal samples of sheep from Inner Mongolia, China exhibited predatory activity;
however, only a single strain was successfully purified (SF 0459). The SF 0459
strain was characterized by morphological analysis of its conidia and sequencing
of its ITS1-5.8S rDNA-ITS2 region. This strain was identified to be
Monacrosporium salinum (GenBank ID: KP036623). Nematophagous fungus helper
bacteria were found at the interaction points between fungi and nematodes. The
percentage of live T. colubriformis L3 was reduced by 83.79-88.69% based on the
in vitro assay.
PMID- 25847585
TI - Alternatively spliced products lacking exon 12 dominate the expression of fragile
X mental retardation 1 gene in human tissues.
AB - Fragile X mental retardation 1 gene (FMR1) expression is associated with fragile
X syndrome (FXS) and exhibits several splicing products. However, the proportion
of spliced isoforms that are expressed in different tissues remains unclear. In
the present study, long-chain reverse transcription-polymerase chain reaction
with a T cloning-sequencing method was conducted in order to analyze the entire
coding region of the FMR1 gene in human tissues. In particular, FXS-associated
tissues were analyzed, including the brain and testis. Twenty alternatively
spliced isoforms were observed among 271 recombinants, including six novel ones.
The isoform that consisted of the entire FMR1 coding region (ISO1) accounted for
a small proportion of all isoforms. Isoforms lacking exon 12 were the most
abundant. In particular, spliced isoforms ISO7 and ISO17 were the most abundant.
However, their relative abundance varied between the peripheral blood cells, and
the testis and brain tissues. Bioinformatic analyses suggested that exon 12 may
be the sole exon undergoing positive selection. The results of the present study
suggested that the mechanisms underlying alternative splicing (AS) of the FMR1
gene may be more complex. Furthermore, the functions of alternatively spliced
products lacking exon 12 require further investigation. The results of the
present study provide novel insights into the association between AS and the
structure and function of the FMR1 gene.
PMID- 25847588
TI - Expression of sexual ornaments in a polymorphic species: phenotypic variation in
response to environmental risk.
AB - Secondary sexual traits may evolve under the antagonistic context of sexual and
natural selection. In some polymorphic species, these traits are only expressed
during the breeding period and are differently expressed in alternative
phenotypes. However, it is unknown whether such phenotypes exhibit phenotypic
plasticity of seasonal ornamentations in response to environmental pressures such
as in the presence of fish (predation risk). This is an important question to
understand the evolution of polyphenisms. We used facultative paedomorphosis in
newts as a model system because it involves the coexistence of paedomorphs that
retain gills in the adult stage with metamorphs that have undergone
metamorphosis, but also because newts exhibit seasonal sexual traits. Our aim was
therefore to determine the influence of fish on the development of seasonal
ornamentation in the two phenotypes of the palmate newt (Lissotriton helveticus).
During the entire newt breeding period, we assessed the importance of phenotype
and fish presence with an information-theoretic approach. Our results showed that
paedomorphs presented much less developed ornamentation than metamorphs and those
ornamentations varied over time. Fish inhibited the development of sexual traits
but differently between phenotypes: in contrast to metamorphs, paedomorphs lack
the phenotypic plasticity of sexual traits to environmental risk. This study
points out that internal and external parameters act in complex ways in the
expression of seasonal sexual ornamentations and that similar environmental
pressure can induce a contrasted evolution in alternative phenotypes.
PMID- 25847589
TI - PTSD and Sexual Dysfunction in Men and Women.
AB - INTRODUCTION: Difficulties in sexual desire and function often occur in persons
with posttraumatic stress disorder (PTSD), but many questions remain regarding
the mechanisms underlying the occurrence of sexual problems in PTSD. AIM: The aim
of this review was to present a model of sexual dysfunction in PTSD underpinned
by an inability to regulate and redirect the physiological arousal needed for
healthy sexual function away from aversive hyperarousal and intrusive memories.
METHOD: A literature review pertaining to PTSD and sexual function was conducted.
Evidence for the comorbidity of sexual dysfunction and PTSD is presented, and
biological and psychological mechanisms that may underlie this co-occurrence are
proposed. MAIN OUTCOME MEASURES: This manuscript presents evidence of sexual
dysfunction in conjunction with PTSD, and of the neurobiology and
neuroendocrinology of PTSD and sexual function. RESULTS: Sexual dysfunction
following trauma exposure may be mediated by PTSD-related biological, cognitive,
and affective processes. CONCLUSIONS: The treatment of PTSD must include
attention to sexual dysfunction and vice versa.
PMID- 25847590
TI - Misidentifying a tennis racket as keys: object identification in people with age
related macular degeneration.
AB - PURPOSE: Previous studies showed that people with age-related macular
degeneration (AMD) can categorise a pre-defined target object or scene with high
accuracy (above 80%). In these studies participants were asked to detect the
target (e.g. an animal) in serial visual presentation. People with AMD must rely
on peripheral vision which is more adapted to the low resolution required for
detection than for the higher resolution required to identify a specific
exemplar. We investigated the ability of people with central vision loss to
identify photographs of objects and scenes. METHODS: Photographs of isolated
objects, natural scenes and objects in scenes were centrally displayed for 2 s
each. Participants were asked to name the stimuli. We measured accuracy and
naming times in 20 patients with AMD, 15 age-matched and 12 young controls.
RESULTS: Accuracy was lower (by about 30%) and naming times were longer (by about
300 ms) in people with AMD than in age-matched controls in the three categories
of images. Correct identification occurred in 62-66% of the stimuli for patients.
More than 20% of the misidentifications resulted from a structural and/or
semantic similarity between the object and the name (e.g. spectacles for dog
plates or dolphin for shark). Accuracy and naming times did not differ
significantly between young and older normally sighted participants indicating
that the deficits resulted from pathology rather than to normal ageing.
CONCLUSIONS: These results show that, in contrast to performance for
categorisation of a single pre-defined target, people with central vision loss
are impaired at identifying various objects and scenes. The decrease in accuracy
and the increase in response times in patients with AMD indicate that peripheral
vision might be sufficient for object and scene categorisation but not for
precise scene or object identification.
PMID- 25847596
TI - Odor fingerprinting of Listeria monocytogenes recognized by SPME-GC-MS and E
nose.
AB - Microorganisms can produce species-specific microbial volatile organic compounds
(MVOCs), or odor compounds, which can be characterized by odor fingerprinting.
The objective of this study was to characterize the odor fingerprint of Listeria
monocytogenes. Solid-phase microextraction-gas chromatography-mass spectrometry
(SPME-GC-MS) and electronic nose (E-nose) were used to recognize the MVOCs of L.
monocytogenes in pure culture medium. The main MVOCs of L. monocytogenes were
identified by SPME-GC-MS analysis as alcohols, aldehydes, ketones, alkanes, and
heterocyclics, among which the relative peak area of one compound, 3-hydroxy-2
butanone, increased along with the growth of L. monocytogenes. The odor
fingerprint of L. monocytogenes at different growth stages could be clearly
discriminated by E-nose. In addition, E-nose signals had a very good linear
relationship with the concentration of this bacterium (R(2) = 0.9937). Our study
may help to establish the analysis of the odor fingerprint of microorganisms as a
potential routine method in microbiology.
PMID- 25847597
TI - Stearidonic acid, a plant-based dietary fatty acid, enhances the chemosensitivity
of canine lymphoid tumor cells.
AB - Lymphoma is the most common hematopoietic tumor in dogs and humans, with similar
pathogenesis and therapeutic responses. Anticancer drugs like vincristine (VCR)
and doxorubicin (DOX) are often used in treating lymphoma. However, the cure rate
is generally poor due to chemoresistance. Here, we sought to determine whether
stearidonic acid (SDA), a plant-based dietary fatty acid, sensitizes
chemoresistant canine lymphoid-tumor cells. GL-1 B-cell lymphoid-tumor cells were
found to be highly sensitive to the antitumor-activity of VCR and DOX, while OSW
T-cell and 17-71 B-cell lymphoid-tumor cells were moderately and fully resistant,
respectively. SDA, at its non-toxic concentrations, significantly promoted the
antitumor action of VCR and DOX in both OSW and 17-71 cells. SDA-mediated
chemosensitization was associated with SDA inhibition of P-glycoprotein (P-gp)
function. This was confirmed in HEK293 cells stably expressing P-gp as well as by
increased binding-affinity of SDA to P-gp in P-gp docking analysis. SDA at its
chemosensitizing concentrations did not affect the viability of healthy dog
peripheral blood mononuclear cells, suggesting that SDA is non-toxic to normal
dog peripheral blood leucocytes at its chemosensitizing concentrations. Our study
identifies a novel dietary fatty acid that may be used as a dietary supplement in
combination with chemotherapy to promote the antitumor efficacy of the
chemotherapy drugs in dogs and possibly in humans with chemoresistant lymphoma.
PMID- 25847598
TI - The role of Cas-L/NEDD9 as a regulator of collagen-induced arthritis in a murine
model.
AB - Cas-L/NEDD9 is a cytoplasmic docking protein downstream of beta1 integrin
mediated signaling pathway and is essential for cellular migration and beta1
integrin-mediated costimulation of T cells. We previously found that increased
number of Cas-L positive leukocytes migrated into the inflamed joints of HTLV-I
tax transgenic mice which spontaneously develop polyarthritis, suggesting a role
of Cas-L in rheumatoid arthritis (RA) pathophysiology. Our current study expanded
these findings on the role of Cas-L/NEDD9 in the development of RA by analyzing
the pathophysiological changes in a Nedd9(-/-) mouse collagen-induced arthritis
(CIA) model. Nedd9(-/-) mice exhibited a decrease in arthritis severity as
compared to Nedd9(+/+) mice. In addition, as being conducted bone marrow
transplantation experiments with a CIA model, Nedd9(-/-)->Nedd9(+/+) transplant
showed a decrease in the incidence and severity score of arthritis, compared to
those of Nedd9(+/+)->Nedd9(-/-) transplant. For analysis of serum levels of
various cytokines, IL-1beta, IL-6, IL-17, TNF-alpha, IFN-gamma and anti-collagen
antibody were decreased, while IL-4 and IL-10 levels were increased, in Nedd9(-/
) mice as compared to those in Nedd9(+/+) mice. Furthermore, collagen-mediated
cellular responses of lymphocytes isolated from spleen or affected lymph nodes of
Nedd9(-/-) mice were reduced. Our results strongly suggest that Cas-L/NEDD9 plays
a pivotal role in the pathophysiology of CIA, and that Cas-L/NEDD9 may be a
potential molecular target for the treatment of RA.
PMID- 25847599
TI - Proliferation and osteogenic response of MC3T3-E1 pre-osteoblastic cells on
porous zirconia ceramics stabilized with magnesia or yttria.
AB - Dense zirconia ceramics are used in bone applications due to their mechanical
strength and biocompatibility, but lack osseointegration. A porous interface in
contact with bone tissue may lead to better bone bonding but the biological
properties of porous zirconia are not widely explored. The present study focuses
on the manufacturing of an yttria- (YSZ) and a magnesia-stabilized (MgSZ) porous
zirconia, and on their in vitro biological investigation. The sintered ceramics
had similar characteristics of porosity, pore size and interconnectivity. Their
elastic moduli and compressive strength values were within the range of the
values of human cortical bone. MC3T3-E1 pre-osteoblasts were used to investigate
the proliferation, alkaline phosphatase (ALP) activity, collagen deposition and
expression profile of four genes involved in bone metabolism of cells on porous
ceramics. Scanning electron and fluorescence microscopy were employed to
visualize cell morphology and growth. Pre-osteoblasts adhered well on both
ceramics but cell numbers on YSZ were higher. Cells exhibited an increase in ALP
activity and collagen deposition after 14 days on both MgSZ and YSZ, with higher
levels on YSZ. Real-time quantitative polymerase chain reaction (qPCR) showed
that the expression of bone sialoprotein (Bsp) and collagen type I (col1aI) were
significantly higher on YSZ. No significant differences were found in their
ability to regulate the early gene expression of Runx2 and Alp. Nevertheless, the
biomineralized calcium content was similar on both ceramics after 21 days,
indicating that despite chemical differences, both scaffolds direct the pre
osteoblasts toward a mature state capable of mineralizing the extracellular
matrix.
PMID- 25847600
TI - Josef Rudinger Memorial Lecture: Use of peptides to modulate protein-protein
interactions.
AB - Peptides are destined to play a major role as therapeutic agents. My laboratory
is contributing to speeding up this process. On the one hand, we devote efforts
to studying the molecular details and dynamics of the events that occur during
molecular recognition at protein surfaces. We succeeded to design and synthesize
peptides able to modulate these recognition events either permanently or in
response to light. On the other hand, we are discovering and designing peptides
able to cross biological barriers. Our aim is to use these peptides as shuttles
for targeting therapeutic agents to organs, tissues, or cells, with a special
emphasis on drug delivery to the brain.
PMID- 25847601
TI - Successful treatment of relapsed anaplastic large cell lymphoma with vinblastine
monotherapy and allo-HSCT with reduced intensity conditioning regimen.
AB - Relapsed anaplastic large cell lymphoma (ALCL) is chemosensitive, but recurrence
is common. Although vinblastine (VLB) monotherapy is an effective treatment for
relapsed ALCL, the optimal treatment duration is unknown, and some patients
experience further relapse after completing the treatment. Allogeneic
hematopoietic stem cell transplantation (allo-HSCT) is also an effective
treatment for relapsed ALCL, although transplant-related toxicity is a problem.
Here, we report an 11-year-old patient with relapsed ALCL who underwent induction
therapy with VLB monotherapy and achieved complete remission (CR) after 12
courses. CR was confirmed on positron emission tomography-computed tomography.
The patient then underwent allo-HSCT with reduced intensity conditioning
(fludarabine, melphalan, and low-dose total body irradiation). He developed grade
II acute graft-versus-host disease (GVHD), which was successfully treated with
methylprednisolone. There was no evidence of chronic GVHD. He has remained in CR
without any complications for 19 months after allo-HSCT.
PMID- 25847602
TI - Design, synthesis, antiviral activity and three-dimensional quantitative
structure-activity relationship study of novel 1,4-pentadien-3-one derivatives
containing the 1,3,4-oxadiazole moiety.
AB - BACKGROUND: 1,4-Pentadien-3-one and 1,3,4-oxadiazole derivatives possess good
antiviral activities, and their substructure units are usually used in antiviral
agent design. In order to discover novel molecules with high antiviral
activities, a series of 1,4-pentadien-3-one derivatives containing the 1,3,4
oxadiazole moiety were designed and synthesised. RESULTS: Bioassays showed that
most of the title compounds exhibited good inhibitory activities against tobacco
mosaic virus (TMV) in vivo. The compound 8f possessing the best protective
activity against TMV had an EC50 value of 135.56 mg L(-1) , which was superior to
that of ribavirin (435.99 mg L(-1) ). Comparative molecular field analysis
(CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques
were used in three-dimensional quantitative structure-activity relationship (3D
QSAR) studies of protective activities, with values of q(2) and r(2) for the
CoMFA and CoMSIA models of 0.751 and 0.775 and 0.936 and 0.925 respectively.
Compound 8k with higher protective activity (EC50 = 123.53 mg L(-1) ) according
to bioassay was designed and synthesised on the basis of the 3D-QSAR models.
CONCLUSION: Some of the title compounds displayed good antiviral activities. 3D
QSAR models revealed that the appropriate compact electron-withdrawing and
hydrophobic group at the benzene ring could enhance antiviral activity. These
results could provide important structural insights for the design of highly
active 1,4-pentadien-3-one derivatives.
PMID- 25847603
TI - An amphetamine isomer whose efficacy and safety in humans has never been studied,
beta-methylphenylethylamine (BMPEA), is found in multiple dietary supplements.
AB - The amphetamine isomer beta-methylphenylethylamine (BMPEA) was first synthesized
in the early 1930s, but its efficacy and safety in humans has not been studied.
Recently, the United States Food and Drug Administration (FDA) detected BMPEA in
dietary supplements labelled as containing Acacia rigidula. Over a year after the
FDA reported its findings, we analyzed Acacia rigidula dietary supplements to
determine if BMPEA had been removed. Supplements were analyzed using liquid
chromatography-quadrupole time-of-flight mass spectrometry. Diluted methanolic
extract from each supplement was run three times and each data set obtained was
analyzed using Agilent MassHunter Qualitative Analysis. The presence of BMPEA was
confirmed by accurate mass, retention time and mass spectra match against a
reference standard. Quantification of BMPEA was determined using an eight-point
calibration curve of spiked standard to a matrix blank. Twenty-one brands of
Acacia rigidula supplements were analyzed. More than half (11/21; 52.4%) of the
Acacia rigidula supplement brands contained BMPEA. The stimulant was present at
quantities such that consumers following recommended maximum daily servings would
consume a maximum of 93.7 mg of BMPEA per day. Consumers of Acacia rigidula
supplements may be exposed to pharmacological dosages of an amphetamine isomer
that lacks evidence of safety in humans. The FDA should immediately warn
consumers about BMPEA and take aggressive enforcement action to eliminate BMPEA
in dietary supplements. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 25847604
TI - Prostate-specific antigen-based prostate cancer screening: Past and future.
AB - Prostate-specific antigen-based prostate cancer screening remains a controversial
topic. Up to now, there is worldwide consensus on the statement that the harms of
population-based screening, mainly as a result of overdiagnosis (the detection of
clinically insignificant tumors that would have never caused any symptoms),
outweigh the benefits. However, worldwide opportunistic screening takes place on
a wide scale. The European Randomized Study of Screening for Prostate Cancer
showed a reduction in prostate cancer mortality through prostate-specific antigen
based-screening. These population-based data need to be individualized in order
to avoid screening in those who cannot benefit and start screening in those who
will. For now, lacking a more optimal screening approach, screening should only
be started after the process of shared decision-making. The focus of future
research is the reduction of unnecessary testing and overdiagnosis by further
research to better biomarkers and the value of the multiparametric magnetic
resonance imaging, potentially combined in already existing prostate-specific
antigen-based multivariate risk prediction models.
PMID- 25847605
TI - Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal
Planning: A Secondary Study of RTOG 0126.
AB - PURPOSE: The purpose of this study was to quantify the frequency and clinical
severity of quality deficiencies in intensity modulated radiation therapy (IMRT)
planning in the Radiation Therapy Oncology Group 0126 protocol. METHODS AND
MATERIALS: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG
0126 were analyzed. To quantify plan quality, we used established knowledge-based
methods for patient-specific dose-volume histogram (DVH) prediction of organs at
risk and a Lyman-Kutcher-Burman (LKB) model for grade >=2 rectal complications to
convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model
was validated by fitting dose-response parameters relative to observed
toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk
(difference between clinical and model-predicted NTCP) were used to create a
model for the presumed best practices in the protocol (pDVH0126,top10%). Applying
the resultant model to the entire sample enabled comparisons between DVHs that
patients could have received to DVHs they actually received. Excess risk
quantified the clinical impact of suboptimal planning. Accuracy of pDVH
predictions was validated by replanning 30 of 219 patients (13.7%), including
equal numbers of presumed "high-quality," "low-quality," and randomly sampled
plans. NTCP-predicted toxicities were compared to adverse events on protocol.
RESULTS: Existing models showed that bladder-sparing variations were less
prevalent than rectum quality variations and that increased rectal sparing was
not correlated with target metrics (dose received by 98% and 2% of the PTV,
respectively). Observed toxicities were consistent with current LKB parameters.
Converting DVH and pDVH0126,top10% to rectal NTCPs, we observed 94 of 219
patients (42.9%) with >=5% excess risk, 20 of 219 patients (9.1%) with >=10%
excess risk, and 2 of 219 patients (0.9%) with >=15% excess risk. Replanning
demonstrated the predicted NTCP reductions while maintaining the volume of the
PTV receiving prescription dose. An equivalent sample of high-quality plans
showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73
respectively, although these differences were not significant (P=.21) due to
insufficient statistical power in this retrospective study. CONCLUSIONS: Plan
quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for
rectal complications.
PMID- 25847606
TI - Sparing healthy tissue and increasing tumor dose using bayesian modeling of
geometric uncertainties for planning target volume personalization.
AB - OBJECTIVE: To develop a mathematical tool that can update a patient's planning
target volume (PTV) partway through a course of radiation therapy to more
precisely target the tumor for the remainder of treatment and reduce dose to
surrounding healthy tissue. METHODS AND MATERIALS: Daily on-board imaging was
used to collect large datasets of displacements for patients undergoing external
beam radiation therapy for solid tumors. Bayesian statistical modeling of these
geometric uncertainties was used to optimally trade off between displacement data
collected from previously treated patients and the progressively accumulating
data from a patient currently partway through treatment, to optimally predict
future displacements for that patient. These predictions were used to update the
PTV position and margin width for the remainder of treatment, such that the
clinical target volume (CTV) was more precisely targeted. RESULTS: Software
simulation of dose to CTV and normal tissue for 2 real prostate displacement
datasets consisting of 146 and 290 patients treated with a minimum of 30
fractions each showed that re-evaluating the PTV position and margin width after
8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively,
while maintaining CTV dose. CONCLUSION: Incorporating patient-specific
displacement patterns from early in a course of treatment allows PTV adaptation
for the remainder of treatment. This substantially reduces the dose to healthy
tissues and thus can reduce radiation therapy-induced toxicities, improving
patient outcomes.
PMID- 25847607
TI - Near Real-Time Assessment of Anatomic and Dosimetric Variations for Head and Neck
Radiation Therapy via Graphics Processing Unit-based Dose Deformation Framework.
AB - PURPOSE: The purpose of this study was to systematically monitor anatomic
variations and their dosimetric consequences during intensity modulated radiation
therapy (IMRT) for head and neck (H&N) cancer by using a graphics processing unit
(GPU)-based deformable image registration (DIR) framework. METHODS AND MATERIALS:
Eleven IMRT H&N patients undergoing IMRT with daily megavoltage computed
tomography (CT) and weekly kilovoltage CT (kVCT) scans were included in this
analysis. Pretreatment kVCTs were automatically registered with their
corresponding planning CTs through a GPU-based DIR framework. The deformation of
each contoured structure in the H&N region was computed to account for nonrigid
change in the patient setup. The Jacobian determinant of the planning target
volumes and the surrounding critical structures were used to quantify anatomical
volume changes. The actual delivered dose was calculated accounting for the organ
deformation. The dose distribution uncertainties due to registration errors were
estimated using a landmark-based gamma evaluation. RESULTS: Dramatic
interfractional anatomic changes were observed. During the treatment course of 6
to 7 weeks, the parotid gland volumes changed up to 34.7%, and the center-of-mass
displacement of the 2 parotid glands varied in the range of 0.9 to 8.8 mm. For
the primary treatment volume, the cumulative minimum and mean and equivalent
uniform doses assessed by the weekly kVCTs were lower than the planned doses by
up to 14.9% (P=.14), 2% (P=.39), and 7.3% (P=.05), respectively. The cumulative
mean doses were significantly higher than the planned dose for the left parotid
(P=.03) and right parotid glands (P=.006). The computation including DIR and dose
accumulation was ultrafast (~45 seconds) with registration accuracy at the
subvoxel level. CONCLUSIONS: A systematic analysis of anatomic variations in the
H&N region and their dosimetric consequences is critical in improving treatment
efficacy. Nearly real-time assessment of anatomic and dosimetric variations is
feasible using the GPU-based DIR framework. Clinical implementation of this
technology may enable timely plan adaptation and improved outcome.
PMID- 25847608
TI - Biomonitoring of metal exposure in children in a northern city of Japan.
PMID- 25847609
TI - Caesarean Section has no impact on lung function at the age of 15 years.
AB - BACKGROUND: Epidemiological studies and meta-analyses have shown an increased
risk of childhood asthma for children born by Caesarean Section (C-Section).
OBJECTIVE: To investigate the effect of delivery by C-Section on lung function
and asthma in adolescence in a population-based prospective birth cohort of
healthy full term newborns. METHODS: Questionnaire data on mode of delivery and
asthma as well as spirometric measurements were available for 1850 adolescents at
the age of 15 years, who participated in a follow-up examination of the GINIplus
study. Linear regression models were used to examine associations between mode of
delivery and lung function parameters. Two reference populations (Lunokid and
GLI) were used to calculate the standardized z-scores of lung function
parameters. RESULTS: The mean difference in lung function parameters for
adolescents born by C-Section, compared to vaginal delivery was not statistically
significant. The risk for developing asthma by the age of 15 years was not higher
in children born by C-Section-OR: 0.87 (95% CI: 0.57, 1.33) adjusted for sex,
age, study center, and parental education level. CONCLUSION: C-Section was not
associated with impaired lung function or an increased risk of asthma at the age
of 15 years in our birth cohort of healthy full term neonates.
PMID- 25847610
TI - Trabeculectomy versus canaloplasty (TVC study) in the treatment of patients with
open-angle glaucoma: a prospective randomized clinical trial.
AB - PURPOSE: To compare the outcomes of canaloplasty and trabeculectomy in open-angle
glaucoma. METHODS: This prospective, randomized clinical trial included 62
patients who randomly received trabeculectomy (n = 32) or canaloplasty (n = 30)
and were followed up prospectively for 2 years. Primary endpoint was complete
(without medication) and qualified success (with or without medication) defined
as an intraocular pressure (IOP) of <=18 mmHg (definition 1) or IOP <=21 mmHg and
>=20% IOP reduction (definition 2), IOP >=5 mmHg, no vision loss and no further
glaucoma surgery. Secondary endpoints were the absolute IOP reduction, visual
acuity, medication, complications and second surgeries. RESULTS: Surgical
treatment significantly reduced IOP in both groups (p < 0.001). Complete success
was achieved in 74.2% and 39.1% (definition 1, p = 0.01), and 67.7% and 39.1%
(definition 2, p = 0.04) after 2 years in the trabeculectomy and canaloplasty
group, respectively. Mean absolute IOP reduction was 10.8 +/- 6.9 mmHg in the
trabeculectomy and 9.3 +/- 5.7 mmHg in the canaloplasty group after 2 years (p =
0.47). Mean IOP was 11.5 +/- 3.4 mmHg in the trabeculectomy and 14.4 +/- 4.2 mmHg
in the canaloplasty group after 2 years. Following trabeculectomy, complications
were more frequent including hypotony (37.5%), choroidal detachment (12.5%) and
elevated IOP (25.0%). CONCLUSIONS: Trabeculectomy is associated with a stronger
IOP reduction and less need for medication at the cost of a higher rate of
complications. If target pressure is attainable by moderate IOP reduction,
canaloplasty may be considered for its relative ease of postoperative care and
lack of complications.
PMID- 25847611
TI - A rapid, fully non-contact, hybrid system for generating Lamb wave dispersion
curves.
AB - A rapid, fully non-contact, hybrid system which encompasses an air-coupled
transducer (ACT) and a laser Doppler vibrometer (LDV) is presented for profiling
A0 Lamb wave dispersion of an isotropic aluminum plate. The ACT generates
ultrasonic pressure incident upon the surface of the plate. The pressure waves
are partially refracted into the plate. The LDV is employed to measure the out-of
plane velocity of the excited Lamb wave mode at some distances where the Lamb
waves are formed in the plate. The influence of the ACT angle of incidence on
Lamb wave excitation is investigated and Snell's law is used to directly compute
Lamb wave dispersion curves including phase and group velocity dispersion curves
in aluminum plates from incident angles found to generate optimal A0 Lamb wave
mode. The measured curves are compared to results obtained from a two-dimensional
(2-D) Fast Fourier transform (FFT), Morlet wavelet transform (MWT) and
theoretical predictions. It was concluded that the experimental results obtained
using Snell's law concept are well in accordance with the theoretical solutions.
The high degree of accuracy in the measured data with the theoretical results
proved a high sensitivity of the air-coupled and laser ultrasound in
characterizing Lamb wave dispersion in plate-like structures. The proposed non
contact hybrid system can effectively characterize the dispersive relation
without knowledge of neither the materials characteristics nor the mathematical
model.
PMID- 25847612
TI - Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits
inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3
inflammasome pathway.
AB - Hepatic fibrosis is concomitant with liver inflammation, which has been
highlighted as significant treatment of chronic liver disease. We previously
demonstrated that tetramethylpyrazine (TMP), the effective component of
Ligusticum chuanxiong Hort, can inhibit the activation of HSCs and consequential
anti-hepatic fibrosis. In this study, our work demonstrated that TMP improved
liver histological architecture, decreased hepatic enzyme levels and attenuated
collagen deposition in the rat fibrotic liver. In addition, TMP significantly
protected the liver from CCl4-caused injury and fibrogenesis by suppressing
inflammation with reducing levels of inflammatory cytokines, including tumor
necrosis factor-alpha (TNF-alpha), NLRP3, nuclear factor-kappa B (NF-kappaB) and
interleukin-1beta (IL-1beta). Experiments in vitro showed that TMP inhibited
inflammatory cytokine expression in HSCs associated with disrupting platelet
derived growth factor-b receptor (PDGF-betaR)/NLRP3/caspase1 pathway. These data
collectively indicate that TMP can attenuate liver inflammation in liver fibrosis
and possibly by targeting HSCs via PDGF-betaR/NLRP3/caspase1 pathway. It provides
novel mechanistic insights into TMP as a potential therapeutic remedy for hepatic
fibrosis.
PMID- 25847613
TI - Rocuronium and sugammadex under TOF monitoring on mECT.
PMID- 25847614
TI - Ultrasound imaging of the musculocutaneous nerve of infants, preschool children,
and school children.
AB - The purpose of this imaging study was to investigate whether the musculocutaneous
nerve could be visualized ultrasonographically in childhood and to assess how its
visualization changes with age. Forty-two children participated in this
prospective imaging study. The musculocutaneous nerve was sought both proximally
(near the axillary artery) and distally (within the coracobrachialis muscle) by
use of an linear ultrasound probe. Location of the musculocutaneous nerve was
good (93 %) for all the children, both proximally and distally. For school-aged
children, distal visualization of the musculocutaneous nerve reached 100 %. The
musculocutaneous nerve is detectable in childhood by use of ultrasonography;
success of detection was high for all the age groups examined.
PMID- 25847615
TI - Clinical correlates of human leucocyte antigen (HLA)-G in systemic sclerosis.
AB - Human leucocyte antigen (HLA)-G has a tolerogenic function and could play a role
in the pathogenesis of immune-mediated diseases, including systemic sclerosis
(SSc). The aim of this study was to evaluate HLA-G serum expression (sHLA-G) and
the HLA-G gene 14 base pairs (bp) insertion/deletion (del(-)/del(+)) polymorphism
in patients with Ssc, to search for possible associations with clinical and
laboratory variables. sHLA-G was measured by enzyme-linked immunosorbent assay
(ELISA) in sera from 77 patients with SSc and 32 healthy donors (HD); the 14 bp
del(-)/del(+) polymorphism was evaluated by polymerase chain reaction (PCR)
amplification of peripheral blood mononuclear cells (PBMC) genomic DNA. Receiver
operating characteristics (ROC) analysis identified the HLA-G cut-off that best
discriminated dichotomized clinical and serological variables, that was
subsequently employed to subdivide SSc patients into HLA-G high (HLA-G(+)) and
low (HLA-G(-)) profile groups. sHLA-G were not statistically different between
SSc patients and HD, nor between distinct SSc autoantibody subsets. Subdividing
SSc patients by HLA-G positivity or negativity yielded significant differences
for the modified Rodnan skin score (mRss) (P = 0.032), 'general' (P = 0.031) and
'kidney' (P = 0.028) Medsger severity scores (MSS) and disease activity index,
and especially Delta heart/lung (P = 0.005). A worse 'general' MSS (P = 0.002)
and Delta heart/lung (P = 0.011) were more frequent in the low sHLA-G group.
These two variables and mRss were associated with sHLA-G levels at logistic
regression analysis. Treatment had no influence on sHLA-G. Moreover, a higher
frequency of scleredema was detected in the del(+)/del(+) than the del(-)/del(+)
group (P = 0.04). These data suggest modulatory effects of sHLA-G on SSc.
Prospective studies are needed to investigate a role in predicting the disease
course.
PMID- 25847616
TI - Mitochondrially-imported RNA in drug discovery.
AB - The import of nuclear transcribed RNAs into mitochondria is an emerging area that
presents a tremendous opportunity to develop human metabolic therapeutics.
However, our knowledge base is quite limited. Much remains to be discovered
regarding specific RNA localization and mechanisms of import. To identify novel
RNAs imported into mitochondria, all RNAs within the mitochondria were
characterized using next generation sequencing technology. Several nuclear
transcribed RNAs were found within mitochondrial RNA (mtRNA) samples, including
nuclear ribosomal RNAs, gamma satellite RNA and VL30 retroelement RNA. The
presence of these RNAs within mitochondria coupled with RNA sequencing data from
other laboratories investigating mtRNA processing, lead us to hypothesize that
nuclease treatment of mitoplasts is insufficient for removing contaminating
cytoplasmic RNAs. In contrast to traditional methodology, mitochondrial import
was evaluated by qRT-PCR after stepwise removal of the outer mitochondrial
membrane and subsequent lysis of mitochondria. This allowed identification of
RNAs lost from the mitochondria with the same kinetics as mitochondrial DNA
transcribed RNAs. This approach provided an improved evaluation of nuclear RNA
enrichment within mitochondrial membranes to characterize nuclease protection and
mitochondrial import and identify false-positive detection errors. qRT-PCR
results confirmed the presence of VL30 retroelement RNA within mitochondria and
question the hypothesis that the RNA component of RNase P is imported. These
results illustrate a reliable approach for evaluating the presence of RNAs within
mitochondria and open new avenues of investigation relating to mtRNA biology and
in targeting mitochondrial based therapeutics.
PMID- 25847617
TI - Preparation of desiccation-resistant aquatic-living Nostoc flagelliforme
(Cyanophyceae) for potential ecological application.
AB - Nostoc flagelliforme is a terrestrial edible cyanobacterium that grows in arid
and semi-arid steppes. The continued over-exploitation in the last century has
led to a sharp decline of this resource and a severe deterioration of the steppe
ecology. Liquid-cultured N. flagelliforme serves as promising algal 'seeds' for
resource restoration. In this study, macroscopic (or visible) aquatic-living
colonies (MaACs) of N. flagelliforme were developed under weak light and high
nitrogen conditions. In a 24 day shake-flask culture, MaACs were propagated by
about 4.5-fold in biomass without loss of their macro-morphology; at the same
time, the addition of weak UV-B treatment resulted in slightly bigger MaACs.
Polyvinylpyrrolidone (PVP) k30, a water-soluble polymer, was used to generate the
coating around MaACs, and after full desiccation, the coated MaACs could recover
their photosynthetic physiological activity when rehydrated, with 4% PVP k30 for
coating being most effective. In contrast, PVP k30-coated microscopic aquatic
living colonies of N. flagelliforme and non-coated MaACs showed no resistance to
full desiccation. The macroscopic morphology or structure of MaACs should be
crucial for the formation of protection by PVP k30 coating. PVP k30-coated MaACs
were more approaching to actual application for resource restoration.
PMID- 25847618
TI - Influence of morphine on medial prefrontal cortex alpha2 adrenergic system in
passive avoidance learning in rats.
AB - The prelimbic region of the medial prefrontal cortex (mPFC) is a brain area
crucial for memory, attention, and decision making. It has been shown that alpha2
adreneoceptors (alpha2-ARs) play a powerful role in regulating memory and
attention functions in this region. Since many studies have demonstrated the
impairment effect of morphine on memory through mPFC, we aimed to investigate the
possible interaction between alpha2-ARs of the mPFC and morphine induced amnesia
in passive avoidance learning in rats. Animals were bilaterally implanted with
chronic cannulas in the mPFC, trained in the step-through type passive avoidance
task, and tested 24h after training; step-through latencies were measured. Our
data indicate that post-training i.p. administration of morphine (2.5, 5 and
7.5mg/kg) dose-dependently reduced the step-through latency, showing an amnesic
effect. Post-training intra-mPFC administration of yohimbine (an alpha2
adrenergic antagonist, 0.125, 0.25 and 0.5MUg/rat) and clonidine (an alpha2
adrenergic agonist, 0.001, 0.01 and 0.2MUg/rat), dose dependently impaired memory
retrieval. Furthermore, post-training intra-mPFC microinjection of ineffective
doses of yohimbine or clonidine significantly reversed the inhibitory effect of
morphine on memory retrieval. Furthermore, SKF96365 (a presynaptic calcium
channel blocker) reduced yohimbine and showed slight inhibition of clonidine
effect. These results suggest that alpha2-ARs of the mPFC may play an important
role in morphine-induced amnesia.
PMID- 25847619
TI - Antinociceptive, anti-inflammatory and smooth muscle relaxant activities of the
pyrrolo[3,4-d]pyridazinone derivatives: Possible mechanisms of action.
AB - The aim of this study was to evaluate the analgesic as well as anti-inflammatory
activities of the new pyrrolo[3,4-d]pyridazinone derivatives. Moreover, the
present study attempted to assess some of the mechanisms involved in the
pharmacological activity of these compounds. In the previous studies it was shown
that these compounds were highly active in the phenylbenzoquinone-induced
'writhing syndrome' test and had much lower activity in the hot plate, which
indicates that mainly peripheral mechanisms of analgesia are involved in their
effects. In these extended studies the analgesic activity of two tested compounds
(4c, 4f) was confirmed in some animal models of pain. The studied compounds
showed a significant and dose-related antinociceptive effect in the models of
pain induced by formalin, capsaicin and glutamic acid. Both compounds decreased
the edema formation and one of them (4c) attenuated mechanical hyperalgesia in
carrageenan-induced paw inflammation in rats. Furthermore, both compounds
inhibited cell migration, plasma exudation and nociceptive reaction in zymosan A
induced mouse peritonitis. In the subsequent studies, including experiments on
isolated organs (ileum, trachea, aorta), radioligand assays and biochemical
tests, it was demonstrated that analgesic and anti-inflammatory effects of the
investigated structures are largely due to their competitive antagonism for
histamine H1 receptor. The influence on the level of cAMP in inflammatory cells
(shown in RAW 264.7 macrophages) and subsequent inhibition of cytokine (TNFalpha,
IL-1beta) release can also be one of the important mechanisms of their action.
Moreover some additional mechanisms may also be involved in the eventual
analgesic effect of tested pyrrolo[3,4-d]pyridazinone derivatives.
PMID- 25847620
TI - Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic
activity in mouse hippocampus.
AB - Elevations in neuronal cholesterol have been associated with several degenerative
diseases. An enhanced excitability and synchronous firing in surviving neurons
are among the sequels of neuronal death in these diseases and also in some
epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels,
using a short hairpin RNA to suppress expression of the enzyme cytochrome P450
family 46, subfamily A, polypeptide 1 gene (CYP46A1). This protein hydroxylates
cholesterol and so facilitates transmembrane extrusion. A short hairpin RNA
CYP46A1construction coupled to the adeno-associated virus type 5 was injected
focally and unilaterally into mouse hippocampus. It was selectively expressed
first in neurons of the cornu ammonis (hippocampus) (CA)3a region. Cytoplasmic
and membrane cholesterol increased, and the neuronal soma volume increased and
then decreased before pyramidal cells died. As CA3a pyramidal cells died,
interictal electroencephalographic (EEG) events occurred during exploration and
non-rapid eye movement sleep. With time, neuronal death spread to involve
pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was
correlated with a delayed local expression of phosphorylated tau. Astrocytes were
activated throughout the hippocampus and microglial activation was specific to
regions of neuronal death. CA1 neuronal death was correlated with distinct
aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep,
EEG oscillations at 7-10 Hz (theta) could accelerate to 14-21 Hz (beta) waves.
They were accompanied by low-amplitude, high-frequency oscillations of peak power
at ~300 Hz and a range of 250-350 Hz. Although episodes of EEG acceleration were
not correlated with changes in exploratory behaviour, they were followed in some
animals by structured seizure-like discharges. These data strengthen links
between increased cholesterol, neuronal sclerosis and epileptic behaviour.
PMID- 25847621
TI - Fast 4D flow MRI intracranial segmentation and quantification in tortuous
arteries.
AB - PURPOSE: To describe, validate, and implement a centerline processing scheme
(CPS) for semiautomated segmentation and quantification in carotid siphons of
healthy subjects. 4D flow MRI enables blood flow measurement in all major
cerebral arteries with one scan. Clinical translational hurdles are time
demanding postprocessing and user-dependence induced variability during analysis.
MATERIALS AND METHODS: A CPS for 4D flow data was developed to automatically
separate cerebral artery trees. Flow parameters were quantified at planes along
the centerline oriented perpendicular to the vessel path. At 3T, validation
against 2D phase-contrast (PC) magnetic resonance imaging (MRI) and 4D flow
manual processing was performed on an intracranial flow phantom for constant
flow, while pulsatile flow validation was performed in the internal carotid
artery (ICA) of 10 healthy volunteers. The CPS and 4D manual processing times
were measured and compared. Flow and area measurements were also demonstrated
along the length of the ICA siphon. RESULTS: Phantom measurements for area and
flow were highly correlated between the CPS and 2D measurements (area: R = 0.95,
flow: R = 0.94), while in vivo waveforms were highly correlated (R = 0.93).
Processing time was reduced by a factor of 4.6 compared with manual processing.
Whole ICA measurements revealed a significantly decreased area in the most distal
segment of the carotid siphon (P = 0.0017), with flow unchanged (P = 0.84).
CONCLUSION: This study exhibits fast semiautomated analysis of intracranial 4D
flow MRI. Internal consistency was shown through flow conservation along the
tortuous ICA siphon, which is typically difficult to assess.
PMID- 25847622
TI - The neurocognitive performance of female veterans with posttraumatic stress
disorder.
AB - Neurocognitive problems are common with posttraumatic stress disorder (PTSD) and
are important to understand because of their association with the success of PTSD
treatment and its potential neural correlates. To our knowledge, this is the
first neurocognitive study in an all-female U.S. veteran sample, some of whom had
PTSD. We examined neurocognitive performance and assessed whether learning
deficits, common in PTSD, were associated with executive functioning. Veterans
with PTSD (n = 56) and without (n = 53) were evaluated for psychiatric and
neurocognitive status. The PTSD group had a lower estimated IQ (d = 0.53) and
performed more poorly on all neurocognitive domains (d range = 0.57-0.88), except
verbal retention (d = 0.04). A subset of the 2 groups that were matched on IQ and
demographics similarly demonstrated poorer performance for the PTSD group on all
neurocognitive domains (d range = 0.52-0.79), except verbal retention (d = 0.15).
Within the PTSD group, executive functioning accounted for significant variance
in verbal learning over and above IQ and processing speed (DeltaR(2) = .06), as
well as depression (DeltaR(2) = .07) and PTSD severity (DeltaR(2) = .06). This
study demonstrated that female veterans with PTSD performed more poorly than
females without PTSD on several neurocognitive domains, including verbal
learning, processing speed, and executive functioning. Replication of these
results using a control group of veterans with more similar trauma exposure,
history of mild traumatic brain injury, and psychiatric comorbidities would
solidify these findings.
PMID- 25847623
TI - Vasorelaxation induced by dodoneine is mediated by calcium channels blockade and
carbonic anhydrase inhibition on vascular smooth muscle cells.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Dodoneine (Ddn) is one of the active compounds
identified from Agelanthus dodoneifolius (DC.) Polhill and Wiens, a medicinal
plant used in traditional medicine for the treatment of hypertension. This
dihydropyranone exerts hypotensive and vasorelaxant effects on rats, and two
molecular targets have been characterized: the carbonic anhydrase and the L-type
calcium channel in cardiomyocytes with biochemical and electrophysiological
techniques, respectively. To further evaluate the involvement of these two
molecular targets in vasorelaxation, the effect of Ddn on rat vascular smooth
muscle was investigated. MATERIAL AND METHODS: The effects of Ddn on L-type
calcium current and on resting membrane potential were characterized in A7r5 cell
line using the whole-cell patch-clamp configuration. The molecular identities of
carbonic anhydrase isozymes in smooth muscle cells were examined with RT-PCR.
Vascular response was measured on rat aortic rings in an organ bath apparatus and
the effect of Ddn on intracellular pH was determined by flow cytometry using the
pH-sensitive fluorescent probe BCECF-AM [2,7-Bis-(2-Carboxyethyl)-5-(and-6)
Carboxyfluorescein, Acetoxymethyl Ester]. RESULTS: 100uM Ddn reduced calcium
current density of about 30%. In addition, carbonic anhydrase II, III, XIII and
XIV were shown to be expressed in rat aorta and inhibited in smooth muscle cells
by Ddn. This inhibition resulted in a rise in pHi of about 0.31, leading to KCa
channel activation, thereby inducing membrane hyperpolarization and
vasorelaxation. The results of vascular reactivity experiments obtained with
pharmacological tools acting on the L-type calcium current and carbonic anhydrase
suggest that Ddn produces its vasorelaxant effect via the inhibition of these two
molecular targets. CONCLUSION: This study demonstrates that Ddn induced
vasorelaxation by targeting two proteins involved in the modulation of excitation
contraction coupling: L-type calcium channels and carbonic anhydrase.
PMID- 25847624
TI - Traditional medicine use by cancer patients in Thailand.
AB - ETHNOBOTANICAL RELEVANCE: Cancer patients commonly use traditional medicines (TM)
and in Thailand these are popular for both self-medication and as prescribed by
TM practitioners, and are rarely monitored. A study was conducted at Wat
Khampramong, a Thai Buddhist temple herbal medicine hospice, to document some of
these practices as well as the hospice regime. MATERIALS AND METHODS: Cancer
patients (n = 286) were surveyed shortly after admission as to which TMs they had
previously taken and perceptions of effects experienced. They were also asked to
describe their current symptoms. Treatment at the hospice is built upon an 11
herb anti-cancer formula, yod-ya-mareng, prescribed for all patients, and
ideally, its effects would have been evaluated. However other herbal medicines
and holistic practices are integral to the regime, so instead we attempted to
assess the value of the patients' stay at the hospice by measuring any change in
symptom burden, as they perceived it. Surviving patients (n = 270) were therefore
asked to describe their symptoms again just before leaving. RESULTS: 42% of
patients (120/286; 95% CI 36.4%, 47.8%) had used herbal medicines before their
arrival, with 31.7% (38/120; 95% CI 24%, 40.4%) using several at once. Mixed
effects were reported for these products. After taking the herbal regime at
Khampramong, 77% (208/270 95% CI; 71.7%, 81.7%) reported benefit, and a
comparison of the incidence of the most common (pain, dyspepsia, abdominal or
visceral pain, insomnia, fatigue) showed statistical significance (chi(2) 57.1,
df 7, p < 0.001). CONCLUSIONS: A wide range of TMs is taken by cancer patients in
Thailand and considered to provide more benefit than harm, and this perception
extends to the temple regime. Patients reported a significant reduction in
symptoms after staying at Khampramong, indicating an improvement in quality of
life, the aim of hospices everywhere. Based on this evidence, it is not possible
to justify the use of TM for cancer in general, but this study suggests that
further research is warranted. The uncontrolled use of TMs, many of which are
uncharacterised, raises concerns, and this work also highlights the fact that
validated, robust methods of assessing holistic medical regimes are urgently
needed.
PMID- 25847625
TI - Health-related quality of life after radical prostatectomy depends on patient's
age but not on comorbidities.
AB - PURPOSE: Localized prostate cancer affects younger and healthy patients as well
as older patients with comorbidities. The purpose of this study was to evaluate
the effect of age and comorbidities on the quality-of-life (QoL) course before
and after radical retropubic prostatectomy. PATIENTS AND METHODS: Overall, 374
patients with localized prostate cancer scheduled for radical prostatectomy were
prospectively included. The QoL questionnaire QLQ-C30 (European Organisation for
Research and Treatment of Cancer) was completed 1 day before surgery and 3, 6, 9,
and 12 months after radical prostatectomy. Sexual and urinary functions were not
assessed in this analysis. Subgroups according to age at diagnosis (<=60,>60
to<=70, and>70y) and comorbidities (Charlson scores<=2 and >=3) were defined.
Subgroups were compared using the Wilcoxon-Mann-Whitney test, whereas changes in
a group over time were analyzed with the Wilcoxon signed rank test. RESULTS: In
all patient groups, no change was found 12 months after surgery compared with
preoperative values in global health as well as functioning (role, physical,
cognitive, and social). Emotional functioning improved significantly after
surgery compared with preoperative functioning. Older patients (>70y) had better
emotional and social functioning compared with younger patients (<=60y). The
other scores were comparable between older and younger patients. Global health
and physical, role, cognitive, and social functioning were independent of the
number of comorbidities, although patients with a Charlson score>=3 did worse
regarding fatigue and dyspnoe. CONCLUSION: The QoL of older patients or patients
with multiple comorbidities is not negatively influenced by radical
prostatectomy. This should be considered when discussing the indication for
prostatectomy in older or comorbid patients.
PMID- 25847626
TI - Novel homozygous mutation in KPTN gene causing a familial intellectual disability
macrocephaly syndrome.
AB - Recently, a novel autosomal recessive developmental delay-macrocephaly syndrome
was described caused by homozygous or compound heterozygous mutations in the KPTN
gene. All reported patients belonged to one large Amish kindred. We report on the
second case of KPTN-related syndrome in two Estonian adult sibs. The brother and
sister both have macrocephaly and moderate intellectual disability, and their
verbal abilities are more affected than motor development. No notable minor
anomalies are present. Behavioral problems and a few episodes of seizures were
reported in the brother. Whole exome sequencing carried out from the brother's
DNA sample identified homozygous one-nucleotide frameshift duplication c.665dupA
(p.Q222fs) in the KPTN gene. Homozygosity of both affected sibs and
heterozygosity of parents were confirmed by Sanger sequencing. Thus, we confirm
the pathogenicity of KPTN mutations and further delineate the novel developmental
delay-macrocephaly syndrome. We also support the hypothesis that KPTN-related
syndrome is not restricted to the Amish population.
PMID- 25847627
TI - Erratum to: Analysis of Programmed Death-1 in Patients with Psoriatic Arthritis.
PMID- 25847628
TI - Selecting a prospective test for early detection of diabetic polyneuropathy.
AB - Microneurolysis of entrapped peripheral nerve has the best chance of success when
compression has not created significant axonal loss. The purpose of this study is
to learn the best way to identify potential surgical candidates at the earliest
time for intervention, by examining patients in a clinical setting using
objective, electrodiagnostic nerve conduction studies (NCS), and subjective touch
threshold studies, Semmes-Weinstein monofilaments (SWM) and Pressure-Specified
Sensory DeviceTM (PSSD). Fifty-five patients with diabetic polyneuropathy over
the age of 30 years were included. Neuropathy symptom score was the gold standard
for statistical calculation, with a prevalence of 70%. In the symptomatic
population, prevalence was 64% for NCS (n = 25), 59% for SWM (n = 43), and 88%
for PSSD (n = 51). In the asymptomatic population, prevalence was 70% for NCS,
27% for SWM, and 92% for PSSD. It is concluded that the PSSD is the most
sensitive device of those tested for identifying peripheral neuropathy in an at
risk population of patients.
PMID- 25847629
TI - Novel olfactory ligands via terpene synthases.
AB - A synthetic biology approach to the rational design of analogues of olfactory
ligands by providing unnatural substrates for the enzyme synthesising (S)
germacrene D, an olfactory ligand acting as a plant derived insect repellent, to
produce novel ligands is described as a viable alternative to largely
unsuccessful ligand docking studies. (S)-14,15-Dimethylgermacrene D shows an
unexpected reversal in behavioural activity.
PMID- 25847630
TI - Efficacy of antimicrobial pullulan-based coating to improve internal quality and
shelf-life of chicken eggs during storage.
AB - There has been a growing interest in the use of natural materials as a delivery
mechanism for antimicrobials and coatings in foods. The aim of the present study
was to evaluate the effectiveness of pullulan coatings to improve internal
quality and shelf-life of fresh eggs during 10 wk of storage at 25 and 4 degrees
C. Three treatments of eggs were evaluated as follows; non-coated (control; C),
coated with pullulan (P), and coated with pullulan containing nisin (N). The
effects of the pullulan coatings on microbiological qualities, physical
properties, and freshness parameters were investigated and compared with non
coated eggs. For non-coated eggs, as storage time increased, yolk index, albumen
index, and Haugh unit value decreased and weight loss increased. However,
pullulan coatings (P or N) minimized weight loss (<1.5%) and preserved the
albumen and yolk quality of eggs (with a final B grade) 3 wk longer than non
coated eggs at 25 degrees C. At 4 degrees C, both P- and N-coated eggs went
from AA to A grade after 9 wk and maintained the grade for 10 wk (4 wk longer
than that of non-coated eggs). This study is the first to demonstrate that
pullulan coatings can preserve the internal quality, prolong the shelf-life, and
minimize weight loss of fresh eggs.
PMID- 25847631
TI - Evaluation of tyrosine kinase receptors in brain metastases of clear cell renal
cell carcinoma reveals cMet as a negative prognostic factor.
AB - AIMS: Brain metastases (BMs) of clear cell renal cell carcinoma (ccRCC) are
associated with a dismal prognosis, with limited treatment options. Tyrosine
kinases are relevant 'druggable' biomarkers. The aim of this study was to
evaluate the tyrosine kinase receptors anaplastic lymphoma kinase (ALK),
epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor
alpha (PDGFRA) and cMet in a large series of ccRCC BMs. METHODS AND RESULTS: ALK,
EGFR, PDGFRA and cMet protein expression was determined by immunohistochemistry
in 53 ccRCCs BMs and 12 matched primary tumours. ALK and MET gene status and copy
number alterations of chromosome 7 were studied with fluorescence in-situ
hybridization (FISH). Data on the expression of hypoxia-inducible factor 1alpha
(HIF1alpha) and Ki67 and microvessel density were available from previous
studies. ALK was negative in all analysed specimens. EGFR was overexpressed in 41
of 51 (80.4%) BMs and in seven of eight primary tumours, PDGFRA was overexpressed
in all BMs except one and in all primary tumours, and cMet was expressed in 26 of
50 (52%) BMs and in two of seven primary tumours, and did not correlate with MET
amplification or polysomy 7. cMet was the only parameter associated with
significantly shorter BM-specific survival (median 8 months versus 33 months, P =
0.005, Cox regression). CONCLUSIONS: EGFR, PDGFRA and cMet are commonly
overexpressed in ccRCC BMs. cMet overexpression correlates with significantly
shorter BM-specific survival.
PMID- 25847632
TI - From emergent literacy to reading: how learning to read changes a child's brain.
AB - The ability to comprehend language is uniquely human. Behavioural and
neuroimaging data reinforce the importance of intact oral language as
foundational for the establishment of proficient reading. However, proficient
reading is achieved not only via intact biological systems, but also a
stimulating Home Literacy Environment. CONCLUSION: Behavioural and neuroimaging
correlates for linguistic ability and literacy exposure support the engagement of
neural circuits related to reading acquisition.
PMID- 25847633
TI - Behavioural and cognitive-behavioural interventions for outwardly-directed
aggressive behaviour in people with intellectual disabilities.
AB - BACKGROUND: Outwardly-directed aggressive behaviour is a significant part of
problem behaviours presented by people with intellectual disabilities. Prevalence
rates of up to 50% have been reported in the literature, depending on the
population sampled. Such behaviours often run a long-term course and are a major
cause of social exclusion. This is an update of a previously published systematic
review (see Hassiotis 2004; Hassiotis 2008). OBJECTIVES: To evaluate the efficacy
of behavioural and cognitive-behavioural interventions on outwardly-directed
aggressive behaviour in people with intellectual disabilities when compared to
standard intervention or wait-list controls. SEARCH METHODS: In April 2014 we
searched CENTRAL, Ovid MEDLINE, Embase, and eight other databases. We also
searched two trials registers, checked reference lists, and handsearched relevant
journals to identify any additional trials. SELECTION CRITERIA: We included
studies if more than four participants (children or adults) were allocated by
random or quasi-random methods to either intervention, standard treatment, or
wait-list control groups. DATA COLLECTION AND ANALYSIS: Two review authors
independently identified studies and extracted and assessed the quality of the
data. MAIN RESULTS: We deemed six studies (309 participants), based on adult
populations with intellectual disabilities, suitable for inclusion in the current
version of this review. These studies examined a range of cognitive-behavioural
therapy (CBT) approaches: anger management (three studies (n = 235); one
individual therapy and two group-based); relaxation (one study; n = 12),
mindfulness based on meditation (one study; n = 34), problem solving and
assertiveness training (one study; n = 28). We were unable to include any studies
using behavioural interventions. There were no studies of children.Only one study
reported moderate quality of evidence for outcomes of interest as assessed by the
Grades of Recommendations, Assessment, Development and Evaluation (GRADE)
approach. We judged the evidence for the remaining studies to be of very low to
low quality. Most studies were at risk of bias in two or more domains: one study
did not randomly allocate participants and in two studies the process of
randomisation was unclear; in one study there was no allocation concealment and
in three studies this was unclear; blinding of assessors did not occur in three
studies; incomplete outcome data were presented in one study and unclear in two
studies; there was selective reporting in one study; and other biases were
present in one study and unclear in four studies.Three of the six studies showed
some benefit of the intervention on improving anger ratings. We did not conduct a
meta-analysis, as we considered the studies too heterogeneous to combine (e.g.
due to differences in the types of participants, sample size interventions, and
outcome measures).Follow-up data for anger ratings for both the treatment and
control groups were available for two studies. Only one of these studies (n =
161) had adequate long-term data (10 months), which found some benefit of
treatment at follow-up (continued improvement in anger coping skills as rated by
key workers; moderate-quality evidence).Two studies (n = 192) reported some
evidence that the intervention reduces the number of incidents of aggression and
one study (n = 28) reported evidence that the intervention improved mental health
symptoms.One study investigated the effects of the intervention on quality of
life and cost of health and social care utilisation. This study provided moderate
quality evidence, which suggests that compared to no treatment, behavioural or
cognitive-behavioural interventions do not improve quality of life at 16 weeks (n
= 129) or at 10 months follow-up (n = 140), or reduce the cost of health service
utilisation (n = 133).Only one study (n = 28) assessed adaptive functioning. It
reported evidence that assertiveness and problem-solving training improved
adaptive behaviour.No studies reported data on adverse events. AUTHORS'
CONCLUSIONS: The existing evidence on the effectiveness of behavioural and
cognitive-behavioural interventions on outwardly-directed aggression in children
and adults with intellectual disabilities is limited. There is a paucity of
methodologically sound clinical trials and a lack of long-term follow-up data.
Given the impact of such behaviours on the individual and his or her support
workers, effective interventions are essential. We recommend that randomised
controlled trials of sufficient power are carried out using primary outcomes that
include reduction in outward-directed aggressive behaviour, improvement in
quality of life, and cost effectiveness.
PMID- 25847634
TI - The cost and quality of cancer care.
PMID- 25847635
TI - A new priority for low-income countries: fighting cancer.
PMID- 25847636
TI - Quality-adjusted cost of care: a meaningful way to measure growth in innovation
cost versus the value of health gains.
AB - Technology drives both health care spending and health improvement. Yet policy
makers rarely see measures of cost growth that account for both effects. To fill
this gap, we present the quality-adjusted cost of care, which illustrates cost
growth net of growth in the value of health improvements, measured as survival
gains multiplied by the value of survival. We applied the quality-adjusted cost
of care to two cases. For colorectal cancer, drug cost per patient increased by
$34,493 between 1998 and 2005 as a result of new drug launches, but value from
offsetting health improvements netted a modest $1,377 increase in quality
adjusted cost of care. For multiple myeloma, new therapies increased treatment
cost by $72,937 between 2004 and 2009, but offsetting health benefits lowered
overall quality-adjusted cost of care by $67,863. However, patients with multiple
myeloma on established first-line therapies saw costs rise without corresponding
benefits. All three examples document rapid cost growth, but they provide starkly
different answers to the question of whether society got what it paid for.
PMID- 25847637
TI - Cancer mortality reductions were greatest among countries where cancer care
spending rose the most, 1995-2007.
AB - Health care spending and health outcomes vary markedly across countries, but the
association between spending and outcomes remains unclear. This inevitably raises
questions as to whether continuing growth in spending is justified, especially
relative to the rising cost of cancer care. We compared cancer care across
sixteen countries over time, examining changes in cancer spending and two
measures of cancer mortality (amenable and excess mortality). We found that
compared to low-spending health systems, high-spending systems had consistently
lower cancer mortality in the period 1995-2007. Similarly, we found that the
countries that increased spending the most had a 17 percent decrease in amenable
mortality, compared to 8 percent in the countries with the lowest growth in
cancer spending. For excess mortality, the corresponding decreases were 13
percent and 9 percent. Additionally, the rate of decrease for the countries with
the highest spending growth was faster than the all-country trend. These findings
are consistent with the existence of a link between higher cancer spending and
lower cancer mortality. However, further work is needed to investigate the
mechanisms that underlie this correlation.
PMID- 25847638
TI - How state and federal policies as well as advances in genome science contribute
to the high cost of cancer drugs.
AB - During a time when cancer drug prices are increasing at an unprecedented rate, a
debate has emerged as to whether these drugs continue to provide good value. In
this article I argue that this debate is irrelevant because under today's highly
distorted market, prices will not be set with value considerations in mind. As an
alternative, I suggest considering the "value" of three policy changes-Medicare's
"average sales price plus 6 percent" payment program, laws that require insurance
coverage of all new cancer drugs, and the Affordable Care Act-that are fueling
manufacturers' willingness to set higher prices. More important than these
issues, however, is the revolution that is occurring in molecular biology and its
impact on scientists' ability to detect changes in the cancer genome. The lowered
cost of discovery is driving more competitors into the market, which under
distorted pricing paradoxically encourages drug makers to charge ever higher
prices for their products.
PMID- 25847639
TI - National expenditure for false-positive mammograms and breast cancer
overdiagnoses estimated at $4 billion a year.
AB - Populationwide mammography screening has been associated with a substantial rise
in false-positive mammography findings and breast cancer overdiagnosis. However,
there is a lack of current data on the associated costs in the United States. We
present costs due to false-positive mammograms and breast cancer overdiagnoses
among women ages 40-59, based on expenditure data from a major US health care
insurance plan for 702,154 women in the years 2011-13. The average expenditures
for each false-positive mammogram, invasive breast cancer, and ductal carcinoma
in situ in the twelve months following diagnosis were $852, $51,837 and $12,369,
respectively. This translates to a national cost of $4 billion each year. The
costs associated with false-positive mammograms and breast cancer overdiagnoses
appear to be much higher than previously documented. Screening has the potential
to save lives. However, the economic impact of false-positive mammography results
and breast cancer overdiagnoses must be considered in the debate about the
appropriate populations for screening.
PMID- 25847640
TI - For uninsured cancer patients, outpatient charges can be costly, putting
treatments out of reach.
AB - Reimbursement information for public and private payers has long been available.
However, information about charges-the amounts that providers request before
payments are negotiated-has been scarce, particularly for outpatient care. Using
the new Medicare Provider Utilization and Payment Data Public Use File and other
sources, we evaluated physician charges, reimbursements by Medicare and large
private health plans, and expected patient cost sharing for outpatient oncology
care. In 2012 the average Medicare reimbursement for chemotherapy was 39.6
percent of charges; for private insurance, the share was 55.7 percent. Uninsured
patients faced potential prices for chemotherapy that were 2-43 times as much as
the total Medicare-allowed amount and 2-5 times as much as the private insurance
allowed amount. Charges for outpatient chemotherapy and office visits were
substantially higher than insurer-reimbursed amounts, which is consistent with
previous evidence about hospital charges. The charges for outpatient services
underscore the pressure that the current system places on the people who are
least able to pay. Encouraging rational pricing for health care services will be
an important step toward ensuring access to care for everyone.
PMID- 25847641
TI - Older women with localized breast cancer: costs and survival rates increased
across two time periods.
AB - Significant national attention has been paid to the rising costs of cancer care.
However, few studies have evaluated the association between trends in costs and
survival outcomes. We used the Surveillance, Epidemiology, and End Results (SEER)
Program-Medicare linked database to compare changes in costs and survival rates
over time, among women ages 67-94 who were diagnosed with stage II or III breast
cancer in 1994-96 or 2004-06. We found that median cancer-related costs increased
from $12,335 to $17,396 among women with stage II disease, and from $18,107 to
$32,598 among women with stage III disease. Although the median cost of breast
surgery declined between the two study periods, the median cost of chemo- and
radiation therapy increased substantially, leading to an overall rise in cancer
related costs. Meanwhile, adjusted overall five-year survival improved, from 67.8
percent to 72.5 percent for women with stage II disease and from 38.5 percent to
51.9 percent for those with stage III disease. These findings suggest that
increases in cancer care costs have been accompanied by improved outcomes. Future
work should identify opportunities to optimize efficiency in cancer care.
PMID- 25847642
TI - Wide variation in payments for Medicare beneficiary oncology services suggests
room for practice-level improvement.
AB - In recent years many policy makers have recommended alternative payment models in
medical oncology in order to reduce costs and improve patient outcomes. Yet
information on how oncology practices differ in their use of key service
categories is limited. We measured annual payments for key service categories
delivered to fee-for-service Medicare beneficiaries receiving care from 1,534
medical oncology practices in 2011-12. In 2012, differences in payments per
beneficiary at the seventy-fifth-percentile practice compared to the twenty-fifth
percentile practice were $3,866 for chemotherapy (including administration and
supportive care drugs), $1,872 for acute medical hospitalizations, and $439 for
advanced imaging. Supportive care drugs, bevacizumab, and positron-emission
tomography accounted for the greatest percentage of variation. Average practice
payments for service categories were highly correlated across years but not
correlated with each other, which suggests that service categories may be
affected by different physician practice characteristics. These differences, even
when clinical guidelines exist, demonstrate the potential for quality improvement
that could be accelerated through alternative payment models.
PMID- 25847643
TI - Early diffusion of gene expression profiling in breast cancer patients associated
with areas of high income inequality.
AB - With the Affordable Care Act reducing coverage disparities, social factors could
prominently determine where and for whom innovations first diffuse in health care
markets. Gene expression profiling is a potentially cost-effective innovation
that guides chemotherapy decisions in early-stage breast cancer, but adoption has
been uneven across the United States. Using a sample of commercially insured
women, we evaluated whether income inequality in metropolitan areas was
associated with receipt of gene expression profiling during its initial diffusion
in 2006-07. In areas with high income inequality, gene expression profiling
receipt was higher than elsewhere, but it was associated with a 10.6-percentage
point gap between high- and low-income women. In areas with low rates of income
inequality, gene expression profiling receipt was lower, with no significant
differences by income. Even among insured women, income inequality may indirectly
shape diffusion of gene expression profiling, with benefits accruing to the
highest-income patients in the most unequal places. Policies reducing gene
expression profiling disparities should address low-inequality areas and, in
unequal places, practice settings serving low-income patients.
PMID- 25847644
TI - Uninsurance among young adults continues to decline, particularly in Medicaid
expansion states.
PMID- 25847645
TI - California emergency department visit rates for medical conditions increased
while visit rates for injuries fell, 2005-11.
AB - The emergency department (ED) is the source of most hospital admissions; provides
care for patients with no other point of access to the health care system;
receives advanced care referrals from primary care physicians; and provides
surveillance data on injuries, infectious diseases, violence, and adverse drug
events. Understanding the changes in the profile of disease in the ED can inform
emergency services administration and planning and can provide insight into the
public's health. We analyzed the trends in the diagnoses seen in California EDs
from 2005 to 2011, finding that while the ED visit rate for injuries decreased by
0.7 percent, the rate of ED visits for noninjury diagnoses rose 13.4 percent. We
also found a rise in symptom-related diagnoses, such as abdominal pain, along
with nervous system disorders, gastrointestinal disease, and mental illness.
These trends point out the increasing importance of EDs in providing care for
complex medical cases, as well as the changing nature of illness in the
population needing immediate medical attention.
PMID- 25847646
TI - Minimum-distance requirements could harm high-performing critical-access
hospitals and rural communities.
AB - Since the inception of the Medicare Rural Hospital Flexibility Program in 1997,
over 1,300 rural hospitals have converted to critical-access hospitals, which
entitles them to Medicare cost-based reimbursement instead of reimbursement based
on the hospital prospective payment system (PPS). Several changes to eligibility
for critical-access status have recently been proposed. Most of the changes focus
on mandating that hospitals be located a certain minimum distance from the
nearest hospital. Our study found that critical-access hospitals located within
fifteen miles of another hospital generally are larger, provide better quality,
and are financially stronger compared to critical-access hospitals located
farther from another hospital. Returning to the PPS would have considerable
negative impacts on critical-access hospitals that are located near another
hospital. We conclude that establishing a minimum-distance requirement would
generate modest cost savings for Medicare but would likely be disruptive to the
communities that depend on these hospitals for their health care.
PMID- 25847647
TI - Reduced acute inpatient care was largest savings component of Geisinger Health
System's patient-centered medical home.
AB - Early evidence suggests that the patient-centered medical home has the potential
to improve patient outcomes while reducing the cost of care. However, it is
unclear how this care model achieves such desirable results, particularly its
impact on cost. We estimated cost savings associated with Geisinger Health
System's patient-centered medical home clinics by examining longitudinal clinic
level claims data from elderly Medicare patients attending the clinics over a
ninety-month period (2006 through the first half of 2013). We also used these
data to deconstruct savings into its main components (inpatient, outpatient,
professional, and prescription drugs). During this period, total costs associated
with patient-centered medical home exposure declined by approximately 7.9
percent; the largest source of this savings was acute inpatient care ($34, or 19
percent savings per member per month), which accounts for about 64 percent of the
total estimated savings. This finding is further supported by the fact that
longer exposure was also associated with lower acute inpatient admission rates.
The results of this study suggest that patient-centered medical homes can lead to
sustainable, long-term improvements in patient health outcomes and the cost of
care.
PMID- 25847648
TI - Michigan's fee-for-value physician incentive program reduces spending and
improves quality in primary care.
AB - As policy makers and others seek to reduce health care cost growth while
improving health care quality, one approach gaining momentum is fee-for-value
reimbursement. This payment strategy maintains the traditional fee-for-service
arrangement but includes quality and spending incentives. We examined Blue Cross
Blue Shield of Michigan's Physician Group Incentive Program, which uses a fee-for
value approach focused on primary care physicians. We analyzed the program's
impact on quality and spending from 2008 to 2011 for over three million
beneficiaries in over 11,000 physician practices. Participation in the incentive
program was associated with approximately 1.1 percent lower total spending for
adults (5.1 percent lower for children) and the same or improved performance on
eleven of fourteen quality measures over time. Our findings contribute to the
growing body of evidence about the potential effectiveness of models that align
payment with cost and quality performance, and they demonstrate that it is
possible to transform reimbursement within a fee-for-service framework to
encourage and incentivize physicians to provide high-quality care, while also
reducing costs.
PMID- 25847649
TI - Care coordination program for Washington State Medicaid enrollees reduced
inpatient hospital costs.
AB - Managing clinically complex populations poses a major challenge for state
agencies trying to control health care costs and improve quality of care for
Medicaid beneficiaries. In Washington State a care coordination intervention, the
Chronic Care Management program, was implemented for clinically complex Medicaid
beneficiaries who met risk criteria defined by a predictive modeling algorithm.
We used propensity score matching to evaluate the program's impact on health care
spending and utilization and mortality. We found large and significant reductions
in inpatient hospital costs ($318 per member per month) among patients who used
the program. The estimated reduction in overall medical costs of $248 per member
per month exceeded the cost of the intervention but did not reach statistical
significance. These results suggest that well-designed targeted care coordination
services could reduce health care spending for Medicaid beneficiaries with
complex health care needs.
PMID- 25847650
TI - Making multipayer reform work: what can be learned from medical home initiatives.
AB - Multipayer collaboratives of all types will encounter legal, logistical, and
often political obstacles that multipayer medical home initiatives have already
overcome. The seventeen multipayer medical home initiatives launched between 2008
and 2014 all navigated four critical decision-making points: convening
stakeholders; establishing provider participation criteria; determining payment;
and measuring performance. Although we observed trends toward voluntary payer
participation and more flexible participation criteria for both payers and
providers, initiatives continue to vary widely, each shaped largely by its
insurance market and policy environment. Medical home initiatives across the
United States are demonstrating that multipayer reform, although complex and
difficult to implement, is feasible when committed stakeholders negotiate
strategies that are responsive to the local context. Their experiences can
inform, and perhaps expedite, negotiations in current and future multipayer
collaborations.
PMID- 25847651
TI - Large performance incentives had the greatest impact on providers whose quality
metrics were lowest at baseline.
AB - This study examined the impact of Fairview Health Services' primary care provider
compensation model, in which 40 percent of compensation was based on clinic-level
quality outcomes. Fairview Health Services is a Pioneer accountable care
organization in Minnesota. Using publicly reported performance data from 2010 and
2012, we found that Fairview's improvement in quality metrics was not greater
than the improvement in other comparable Minnesota medical groups. An analysis of
Fairview's administrative data found that the largest predictor of improvement
over the first two years of the compensation model was primary care providers'
baseline quality performance. Providers whose baseline performance was in the
lowest tertile improved three times more, on average, across the three quality
metrics studied than those in the middle tertile, and almost six times more than
those in the top tertile. As a result, there was a narrowing of variation in
performance across all primary care providers at Fairview and a narrowing of the
gap in quality between providers who treated the highest-income patient panels
and those who treated the lowest-income panels. The large quality incentive fell
short of its overall quality improvement aim. However, the results suggest that
payment reform may help narrow variation in primary care provider performance,
which can translate into narrowing socioeconomic disparities.
PMID- 25847652
TI - Efficacy and safety concerns are important reasons why the FDA requires multiple
reviews before approval of new drugs.
AB - The regulatory approval of new drugs by the Food and Drug Administration (FDA) is
a long and complex process and often requires multiple cycles of review,
potentially delaying patients' access to new and effective therapeutics. We used
qualitative methods to characterize the safety and efficacy reasons why
applications for novel therapeutics approved by the FDA between 2001 and 2011
required multiple review cycles prior to approval. Among ninety-six applications
approved between 2001 and 2011 that required multiple review cycles, safety
concerns contributed to seventy-four (77.1 percent) and efficacy concerns to
forty-three (44.8 percent). Our study suggests that multiple review cycles appear
to play an important role in allowing the FDA to protect public health and in
ensuring adequate understanding of clinical benefits and risks prior to approval.
PMID- 25847653
TI - Insensible losses: when the medical community forgets the family.
PMID- 25847654
TI - Foundation grants on access to primary care.
PMID- 25847656
TI - Home-based medical care and the Triple Aim.
PMID- 25847657
TI - Quality measures for home-based care.
PMID- 25847658
TI - Home-based care: the authors reply.
PMID- 25847659
TI - Errata.
PMID- 25847660
TI - Bis(benzoyloxybenzyl)-DiPPro nucleoside diphosphates of anti-HIV active
nucleoside analogues.
AB - Nucleoside analogues are extensively used as antiviral and anticancer agents.
Their efficiency is dependent on their metabolism into the ultimately active
nucleoside triphosphates. Often one step or even more in the metabolism of the
nucleoside to the triphosphate is inefficient. To overcome this hurdle, prodrugs
of the nucleotides are needed. Bis(acyloxybenzyl)nucleoside diphosphates have
been reported by us as a first example of an efficient nucleoside diphosphate
prodrug (DiPPro nucleotides). Here, the synthesis and the properties of
bis(benzoyloxybenzyl)nucleoside diphosphates of the nucleoside analogues d4T and
AZT are disclosed. The synthesis was achieved by using a
phosphoramidite/oxidation route. In chemical hydrolysis studies, most of the
compounds formed a nucleoside diphosphate. This was confirmed in CEM cell
extracts, although the prodrug stability in extracts was lower than in phosphate
buffer. Furthermore, the stability and the amount of nucleoside diphosphate
formed were dependent on the substituent in the benzoyl moiety. Some of the
compounds were more active against HIV in thymidine kinase-deficient CEM/TK(-)
cells than were d4T or AZT.
PMID- 25847661
TI - Erratum to: Visualization of osseointegration of maxilla and mandible dental
implants.
PMID- 25847662
TI - A knowledge-based algorithm for automatic detection of cephalometric landmarks on
CBCT images.
AB - PURPOSE: Cone-beam computed tomography (CBCT) is now an established component for
3D evaluation and treatment planning of patients with severe malocclusion and
craniofacial deformities. Precision landmark plotting on 3D images for
cephalometric analysis requires considerable effort and time, notwithstanding the
experience of landmark plotting, which raises a need to automate the process of
3D landmark plotting. Therefore, knowledge-based algorithm for automatic
detection of landmarks on 3D CBCT images has been developed and tested. METHODS:
A knowledge-based algorithm was developed in the MATLAB programming environment
to detect 20 cephalometric landmarks. For the automatic detection, landmarks that
are physically adjacent to each other were clustered into groups and were
extracted through a volume of interest (VOI). Relevant contours were detected in
the VOI and landmarks were detected using corresponding mathematical entities.
The standard data for validation were generated using manual marking carried out
by three orthodontists on a dataset of 30 CBCT images as a reference. RESULTS:
Inter-observer ICC for manual landmark identification was found to be excellent
(>0.9) amongst three observers. Euclidean distances between the coordinates of
manual identification and automatic detection through the proposed algorithm of
each landmark were calculated. The overall mean error for the proposed method was
2.01 mm with a standard deviation of 1.23 mm for all the 20 landmarks. The
overall landmark detection accuracy was recorded at 64.67, 82.67 and 90.33 %
within 2-, 3- and 4-mm error range of manual marking, respectively. CONCLUSIONS:
The proposed knowledge-based algorithm for automatic detection of landmarks on 3D
images was able to achieve relatively accurate results than the currently
available algorithm.
PMID- 25847663
TI - Stability, structure and scale: improvements in multi-modal vessel extraction for
SEEG trajectory planning.
AB - PURPOSE: Brain vessels are among the most critical landmarks that need to be
assessed for mitigating surgical risks in stereo-electroencephalography (SEEG)
implantation. Intracranial haemorrhage is the most common complication associated
with implantation, carrying significantly associated morbidity. SEEG planning is
done pre-operatively to identify avascular trajectories for the electrodes. In
current practice, neurosurgeons have no assistance in the planning of electrode
trajectories. There is great interest in developing computer-assisted planning
systems that can optimise the safety profile of electrode trajectories,
maximising the distance to critical structures. This paper presents a method that
integrates the concepts of scale, neighbourhood structure and feature stability
with the aim of improving robustness and accuracy of vessel extraction within a
SEEG planning system. METHODS: The developed method accounts for scale and
vicinity of a voxel by formulating the problem within a multi-scale tensor voting
framework. Feature stability is achieved through a similarity measure that
evaluates the multi-modal consistency in vesselness responses. The proposed
measurement allows the combination of multiple images modalities into a single
image that is used within the planning system to visualise critical vessels.
RESULTS: Twelve paired data sets from two image modalities available within the
planning system were used for evaluation. The mean Dice similarity coefficient
was 0.89 +/- 0.04, representing a statistically significantly improvement when
compared to a semi-automated single human rater, single-modality segmentation
protocol used in clinical practice (0.80 +/- 0.03). CONCLUSIONS: Multi-modal
vessel extraction is superior to semi-automated single-modality segmentation,
indicating the possibility of safer SEEG planning, with reduced patient
morbidity.
PMID- 25847664
TI - Registration by interactive inverse simulation: application for adaptive
radiotherapy.
AB - PURPOSE: This paper introduces a new methodology for semi-automatic registration
of anatomical structure deformations. The contribution is to use an interactive
inverse simulation of physics-based deformable model, computed in real time.
METHODS: The method relies on nonlinear finite element method (FEM) within a
constraint-based framework. Given a set of few registered points provided by the
user, a real-time optimization adapts the boundary conditions and(/or) some
parameters of the FEM in order to obtain the adequate geometrical deformations.
To dramatically fasten the process, the method relies on a projection of the
model in the space of the optimization variables. In this reduced space, a
quadratic programming problem is formulated and solved very quickly. The method
is validated with numerical examples for retrieving some unknown parameters such
as the Young's modulus and some pressures on the boundaries of the model.
RESULTS: The approach is employed in the context of radiotherapy of the neck
where weight loss during the 7 weeks of the therapy modifies the volume of the
anatomical structures and induces large deformations. Indeed, sensitive
structures such as the parotid glands may cross the target volume due to these
deformations which leads to adverse effects for the patient. We thus apply the
approach for the registration of the parotid glands during the radiotherapy of
the head and neck cancer. CONCLUSIONS: The results show how the method could be
used in a clinical routine and be employed in the planning in order to limit the
radiations of these glands.
PMID- 25847665
TI - Brain activation in parietal area during manipulation with a surgical robot
simulator.
AB - PURPOSE: we present an evaluation method to qualify the embodiment caused by the
physical difference between master-slave surgical robots by measuring the
activation of the intraparietal sulcus in the user's brain activity during
surgical robot manipulation. We show the change of embodiment based on the change
of the optical axis-to-target view angle in the surgical simulator to change the
manipulator's appearance in the monitor in terms of hand-eye coordination. The
objective is to explore the change of brain activation according to the change of
the optical axis-to-target view angle. METHODS: In the experiments, we used a
functional near-infrared spectroscopic topography (f-NIRS) brain imaging device
to measure the brain activity of the seven subjects while they moved the hand
controller to insert a curved needle into a target using the manipulator in a
surgical simulator. The experiment was carried out several times with a variety
of optical axis-to-target view angles. RESULTS: Some participants showed a
significant peak (P value = 0.037, F-number = 2.841) when the optical axis-to
target view angle was 75 degrees . CONCLUSIONS: The positional relationship
between the manipulators and endoscope at 75 degrees would be the closest to the
human physical relationship between the hands and eyes.
PMID- 25847666
TI - Open-source image registration for MRI-TRUS fusion-guided prostate interventions.
AB - PURPOSE: We propose two software tools for non-rigid registration of MRI and
transrectal ultrasound (TRUS) images of the prostate. Our ultimate goal is to
develop an open-source solution to support MRI-TRUS fusion image guidance of
prostate interventions, such as targeted biopsy for prostate cancer detection and
focal therapy. It is widely hypothesized that image registration is an essential
component in such systems. METHODS: The two non-rigid registration methods are:
(1) a deformable registration of the prostate segmentation distance maps with B
spline regularization and (2) a finite element-based deformable registration of
the segmentation surfaces in the presence of partial data. We evaluate the
methods retrospectively using clinical patient image data collected during
standard clinical procedures. Computation time and Target Registration Error
(TRE) calculated at the expert-identified anatomical landmarks were used as
quantitative measures for the evaluation. RESULTS: The presented image
registration tools were capable of completing deformable registration computation
within 5 min. Average TRE was approximately 3 mm for both methods, which is
comparable with the slice thickness in our MRI data. Both tools are available
under nonrestrictive open-source license. CONCLUSIONS: We release open-source
tools that may be used for registration during MRI-TRUS-guided prostate
interventions. Our tools implement novel registration approaches and produce
acceptable registration results. We believe these tools will lower the barriers
in development and deployment of interventional research solutions and facilitate
comparison with similar tools.
PMID- 25847667
TI - Bone enhancement in ultrasound using local spectrum variations for guiding
percutaneous scaphoid fracture fixation procedures.
AB - PURPOSE: The scaphoid bone is the most frequently fractured bone in the wrist.
When fracture fixation is indicated, a screw is inserted into the bone either in
an open surgical procedure or percutaneously under fluoroscopic guidance. Due to
the complex geometry of the wrist, fracture fixation is a challenging task.
Fluoroscopic guidance exposes both the patient and the physician to ionizing
radiation. Ultrasound-based guidance has been suggested as a real-time, radiation
free alternative. The main challenge of using ultrasound is the difficulty in
interpreting the images due to the low contrast and noisy nature of the data.
METHODS: We propose a bone enhancement method that exploits local spectrum
features of the ultrasound image. These features are utilized to design a set of
quadrature band-pass filters and subsequently estimate the local phase symmetry,
where high symmetry is expected at the bone locations. We incorporate the shadow
information below the bone surfaces to further enhance the bone responses. The
extracted bone surfaces are then used to register a statistical wrist model to
ultrasound volumes, allowing the localization and interpretation of the scaphoid
bone in the volumes. RESULTS: Feasibility experiments were performed using
phantom and in vivo data. For phantoms, we obtain a surface distance error 1.08
mm and an angular deviation from the main axis of the scaphoid bone smaller than
5 degrees , which are better compared to previously presented approaches.
CONCLUSION: The results are promising for further development of a surgical
guidance system to enable accurate anatomy localization for guiding percutaneous
scaphoid fracture fixations.
PMID- 25847668
TI - Classification approach for automatic laparoscopic video database organization.
AB - PURPOSE: One of the advantages of minimally invasive surgery (MIS) is that the
underlying digitization provides invaluable information regarding the execution
of procedures in various patient-specific conditions. However, such information
can only be obtained conveniently if the laparoscopic video database comes with
semantic annotations, which are typically provided manually by experts.
Considering the growing popularity of MIS, manual annotation becomes a laborious
and costly task. In this paper, we tackle the problem of laparoscopic video
classification, which consists of automatically identifying the type of abdominal
surgery performed in a video. In addition to performing classifications on the
full recordings of the procedures, we also carry out sub-video and video clip
classifications. These classifications are carried out to investigate how many
frames from a video are needed to get a good classification performance and which
parts of the procedures contain more discriminative features. METHOD: Our
classification pipeline is as follows. First, we reject the irrelevant frames
from the videos using the color properties of the video frames. Second, we
extract visual features from the relevant frames. Third, we quantize the features
using several feature encoding methods, i.e., vector quantization, sparse coding
(SC), and Fisher encoding. Fourth, we carry out the classification using support
vector machines. While the sub-video classification is carried out by uniformly
downsampling the video frames, the video clip classification is carried out by
taking three parts of the videos (i.e., beginning, middle, and end) and running
the classification pipeline separately for every video part. Ultimately, we build
our final classification model by combining the features using a multiple kernel
learning (MKL) approach. RESULTS: To carry out the experiments, we use a dataset
containing 208 videos of eight different surgeries performed by 10 different
surgeons. The results show that SC with K-singular value decomposition (K-SVD)
yields the best classification accuracy. The results also demonstrate that the
classification accuracy only decreases by 3 % when solely 60 % of the video
frames are utilized. Furthermore, it is also shown that the end part of the
procedures is the most discriminative part of the surgery. Specifically, by using
only the last 20 % of the video frames, a classification accuracy greater than 70
% can be achieved. Finally, the combination of all features yields the best
performance of 90.38 % accuracy. CONCLUSIONS: The SC with K-SVD provides the best
representation of our videos, yielding the best accuracies for all features. In
terms of information, the end part of the laparoscopic videos is the most
discriminative compared to the other parts of the videos. In addition to their
good performance individually, the features yield even better classification
results when all of them are combined using the MKL approach.
PMID- 25847669
TI - PCA-derived respiratory motion surrogates from X-ray angiograms for percutaneous
coronary interventions.
AB - PURPOSE: Intraoperative coronary motion modeling with motion surrogates enables
prospective motion prediction in X-ray angiograms (XA) for percutaneous coronary
interventions. The motion of coronary arteries is mainly affected by patients
breathing and heartbeat. Purpose of our work is therefore to extract coronary
motion surrogates that are related to respiratory and cardiac motion. In
particular, we focus on respiratory motion surrogates extraction in this paper.
METHODS: We propose a fast automatic method for extracting patient-specific
respiratory motion surrogate from cardiac XA. The method starts with an image
preprocessing step to remove all tubular and curvilinear structures from XA
images, such as vessels and guiding catheters, followed by principal component
analysis on pixel intensities. The respiratory motion surrogate of an XA image is
then obtained by projecting its vessel-removed image onto the first principal
component. RESULTS: This breathing motion surrogate was demonstrated to get high
correlation with ground truth diaphragm motion (correlation coefficient over 0.9
on average). In comparison with other related methods, the method we developed
did not show significant difference (p > 0.05), but did improve robustness and
run faster on monoplane and biplane data in retrospective and prospective
scenarios. CONCLUSIONS: we developed and evaluated a method in extraction of
respiratory motion surrogate from interventional X-ray images that is easy to
implement and runs in real time and thus allows extracting respiratory motion
surrogates during interventions.
PMID- 25847670
TI - Data-driven spatio-temporal RGBD feature encoding for action recognition in
operating rooms.
AB - PURPOSE: Context-aware systems for the operating room (OR) provide the
possibility to significantly improve surgical workflow through various
applications such as efficient OR scheduling, context-sensitive user interfaces,
and automatic transcription of medical procedures. Being an essential element of
such a system, surgical action recognition is thus an important research area. In
this paper, we tackle the problem of classifying surgical actions from video
clips that capture the activities taking place in the OR. METHODS: We acquire
recordings using a multi-view RGBD camera system mounted on the ceiling of a
hybrid OR dedicated to X-ray-based procedures and annotate clips of the
recordings with the corresponding actions. To recognize the surgical actions from
the video clips, we use a classification pipeline based on the bag-of-words (BoW)
approach. We propose a novel feature encoding method that extends the classical
BoW approach. Instead of using the typical rigid grid layout to divide the space
of the feature locations, we propose to learn the layout from the actual 4D
spatio-temporal locations of the visual features. This results in a data-driven
and non-rigid layout which retains more spatio-temporal information compared to
the rigid counterpart. RESULTS: We classify multi-view video clips from a new
dataset generated from 11-day recordings of real operations. This dataset is
composed of 1734 video clips of 15 actions. These include generic actions (e.g.,
moving patient to the OR bed) and actions specific to the vertebroplasty
procedure (e.g., hammering). The experiments show that the proposed non-rigid
feature encoding method performs better than the rigid encoding one. The
classifier's accuracy is increased by over 4 %, from 81.08 to 85.53 %.
CONCLUSION: The combination of both intensity and depth information from the RGBD
data provides more discriminative power in carrying out the surgical action
recognition task as compared to using either one of them alone. Furthermore, the
proposed non-rigid spatio-temporal feature encoding scheme provides more
discriminative histogram representations than the rigid counterpart. To the best
of our knowledge, this is also the first work that presents action recognition
results on multi-view RGBD data recorded in the OR.
PMID- 25847671
TI - Toward knowledge-based liver surgery: holistic information processing for
surgical decision support.
AB - PURPOSE: Malignant neoplasms of the liver are among the most frequent cancers
worldwide. Given the diversity of options for liver cancer therapy, the choice of
treatment depends on various parameters including patient condition, tumor size
and location, liver function, and previous interventions. To address this issue,
we present the first approach to treatment strategy planning based on holistic
processing of patient-individual data, practical knowledge (i.e., case
knowledge), and factual knowledge (e.g., clinical guidelines and studies).
METHODS: The contributions of this paper are as follows: (1) a formalized dynamic
patient model that incorporates all the heterogeneous data acquired for a
specific patient in the whole course of disease treatment; (2) a concept for
formalizing factual knowledge; and (3) a technical infrastructure that enables
storing, accessing, and processing of heterogeneous data to support clinical
decision making. RESULTS: Our patient model, which currently covers 602 patient
individual parameters, was successfully instantiated for 184 patients. It was
sufficiently comprehensive to serve as the basis for the formalization of a total
of 72 rules extracted from studies on patients with colorectal liver metastases
or hepatocellular carcinoma. For a subset of 70 patients with these diagnoses,
the system derived an average of [Formula: see text] assertions per patient.
CONCLUSION: The proposed concept paves the way for holistic treatment strategy
planning by enabling joint storing and processing of heterogeneous data from
various information sources.
PMID- 25847672
TI - Amphiphilic tobramycins with immunomodulatory properties.
AB - Amphiphilic aminoglycosides (AAGs) are an emerging source of antibacterials to
combat infections caused by antibiotic-resistant bacteria. Mode-of-action studies
indicate that AAGs predominately target bacterial membranes, thereby leading to
depolarization and increased permeability. To assess whether AAGs also induce
host-directed immunomodulatory responses, we determined the AAG-dependent
induction of cytokines in macrophages in the absence or presence of
lipopolysaccharide (LPS). Our results show for the first time that AAGs can boost
the innate immune response, specifically the recruitment of immune cells such as
neutrophils required for the resolution of infections. Moreover, AAGs can
selectively control inflammatory responses induced in the presence of endotoxins
to prevent septic shock. In conclusion, our study demonstrates that AAGs possess
multifunctional properties that combine direct antibacterial activity with host
directed clearance effects reminiscent of those of host-defense peptides.
PMID- 25847673
TI - A comparative study of the effects of cholesterol and desmosterol on zwitterionic
DPPC model membranes.
AB - Desmosterol is a direct biosynthetic precursor of cholesterol in Bloch
biochemical pathway of cholesterol biosynthesis and differs with cholesterol only
by a double bond in carbon 24. In this study, we aimed to research for the first
time comparative effects of cholesterol and its precursor desmosterol on
dipalmitoyl phosphatidylcholine (DPPC) multilamellar vesicles (MLVs) by utilizing
Fourier transform infrared (FTIR) spectroscopy and differential scanning
calorimetry (DSC). Our DSC studies reveal that with the addition of increasing
desmosterol and cholesterol concentrations into pure DPPC MLVs, the pretransition
disappears, the main phase transition shifts to lower temperatures and then
disappears. While the main phase transition is abolished at 25 mol% concentration
of desmosterol, this disappearance of the main phase transition occurs at
cholesterol concentration above 30 mol%. Our FTIR studies show that both
desmosterol and cholesterol decrease the order in the gel phase, whereas they
increase it in the liquid crystalline phase. Importantly, we found that the
effect of desmosterol on membrane order is weaker than that of cholesterol in
both phases. Moreover, desmosterol and cholesterol increase the dynamics of DPPC
membranes in the gel phase, while they decrease it in the liquid crystalline
phase. Both sterols also induce a decrease in the wavenumber values of the C=O
stretching and PO2(-) antisymmetric double stretching bands of DPPC both in the
gel and liquid crystalline phases, which points out hydrogen bonding in between
the hydroxyl group of both sterols and the carbonyl and phosphate groups of DPPC
membranes.
PMID- 25847675
TI - Anti-inflammatory potential of saponins derived from cultured wild ginseng roots
in lipopolysaccharide-stimulated RAW 264.7 macrophages.
AB - Ginseng, namely the root of Panax ginseng Meyer, is a well-known traditional
medicine that has been used in Asian countries for thousands of years. Ginseng
saponins have been shown to exert a variety of prominent pharmacological effects
in a number of diseases. The aim of the present study was to identify the anti
inflammatory effects of total saponins extracted from cultured wild ginseng roots
(TSWG) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. An elevated
production of nitric oxide (NO) was detected in the RAW 264.7 cells in response
to stimulation with LPS, as shown by NO detection assay using Griess reagent.
However, pre-treatment with TSWG inhibited the production of NO through the
suppression of inducible NO synthase gene expression. Furthermore, the LPS
induced gene expression and production of tumor necrosis factor-alpha (TNF-alpha)
and interleukin-1beta (IL-1beta) were significantly reduced by treatment with
TSWG, as shown by ELISA, and western blot analysis and RT-PCR, respectively. In
the LPS-stimulated RAW 264.7 cells, nuclear factor-kappaB (NF-kappaB) was
translocated from the cytosol to the nucleus, while pre-treatment with TSWG
induced the sequestration of NF-kappaB in the cytosol through the inhibition of
the inhibitor of kappaB degradation, as shown by immunofluorescence staining.
TSWG also contributed to the downregulation of mitogen-activated protein kinases
and Akt in the LPS-stimulated RAW 264.7 cells. Additionally, in the TSWG-treated
RAW 264.7 cells, we observed the activation of nuclear factor (erythroid-derived
2)-like 2 and an increase in heme oxygenase-1 expression; these effects were
associated with the inhibition of the generation of reactive oxygen species. The
results from the present study indicate that TSWG exerts anti-inflammatory and
antioxidant effects, suggesting that TSWG may be an effective therapeutic agent
for inflammatory diseases and prevent cellular damage induced by oxidative
stress.
PMID- 25847674
TI - Microsporidia-host interactions.
AB - Microsporidia comprise one of the largest groups of obligate intracellular
pathogens and can infect virtually all animals, but host response to these fungal
related microbes has been poorly understood. Several new studies of the host
transcriptional response to microsporidia infection have found infection-induced
regulation of genes involved in innate immunity, ubiquitylation, metabolism, and
hormonal signaling. In addition, microsporidia have recently been shown to
exploit host recycling endocytosis for exit from intestinal cells, and to
interact with host degradation pathways. Microsporidia infection has also been
shown to profoundly affect behavior in insect hosts. Altogether, these and other
recent findings are providing much-needed insight into the underlying mechanisms
of microsporidia interaction with host animals.
PMID- 25847676
TI - Development of a method to screen and isolate potential alpha-glucosidase
inhibitors from Panax japonicus C.A. Meyer by ultrafiltration, liquid
chromatography, and counter-current chromatography.
AB - A new assay based on ultrafiltration, liquid chromatography and mass spectrometry
was developed for the rapid screening and identification of the ligands for alpha
glucosidase from the extract of Panax japonicus. Six saponins were identified as
alpha-glucosidase inhibitors. Subsequently, the specific binding ligands, namely,
notoginsenoside R1 , ginsenoside Rb1 , chikusetsusaponin V, chikusetsusaponin IV,
chikusetsusaponin IVa, and ginsenoside Rd (the purities were 94.18, 95.43, 96.09,
93.26, 94.50, 93.86%, respectively) were separated by counter-current
chromatography using two-phase solvent systems composed of tert-butyl methyl
ether, acetonitrile, 0.1% aqueous formic acid (3.8:1.0:4.4, v/v/v) and the
solvent system composed of methylene chloride, isopropanol, methanol, 0.1%
aqueous formic acid (5.8:1.0:6.0:2.2, v/v/v). The results demonstrate that
ultrafiltration, liquid chromatography and mass spectrometry combined with high
speed counter-current chromatography might provide not only a powerful tool for
screening and isolating alpha-glucosidase inhibitors in complex samples but also
a useful platform for discovering bioactive compounds for the prevention and
treatment of diabetes mellitus.
PMID- 25847677
TI - Discrepant trends in income, drinking, and alcohol problems in an emergent
economy: Brazil 2006 to 2012.
AB - BACKGROUND: To examine the association between increases in income and self
reported alcohol consumption, binge drinking, and alcohol problems in 2006 and
2012 in Brazil. METHODS: Participants were interviewed as part of 2 multistage
representative cluster samples of the Brazilian household population between
November 2005 and April 2006 and between November 2011 and March 2012. The number
of current drinkers during these 2 intervals (n = 1,379 and n = 1,907,
respectively) comprised the sample analyzed. Four past-year outcome variables
standard drinks per week, binge drinking, presence of alcohol-related
social/health problems, and DSM-5 alcohol use disorder (AUD)-were estimated
across income, age, and gender groups. Regression models were estimated to
evaluate these and other sociodemographic effects on drinking and problem
outcomes and to test for possible wave by income interactions. RESULTS: Response
rates were 66.4% in 2006 and 77% in 2012. Income increases were seen in virtually
all age-gender subgroups and were particularly pronounced for younger age groups
and older women. Both genders reported increased drinks per week (men: 12.82,
2006; 15.78, 2012; p < 0.01; women: 4.89, 2006; 7.66, 2012; p < 0.001) and
proportion binge drinking (men: 57%, 2006; 66%, 2012; p < 0.05; women: 39%, 2006;
48%, 2012; p < 0.05), although this was not seen in all gender and age groups.
Social/health problem prevalence decreased among men (37%, 2006; 26%, 2012; p <
0.001) and remained the same among women (13%, 2006; 14%, 2012). DSM-5 AUD
decreased among men (34%, 2006; 24%, 2012; p < 0.01) and remained stable among
women (14%, 2006; 16%, 2012). CONCLUSIONS: Brazilian economic development between
2006 and 2012 led to a rise in income in several gender and age groups. Although
not always directly associated with an observed increase in alcohol consumption,
the rise in income may have created a sense of optimism that inhibited a rise in
alcohol-related problems.
PMID- 25847679
TI - Talairach methodology in the era of 3D multimodal imaging: "The song remains the
same," but catchier, and therefore more helpful for clinical decision making and
surgical planning in epilepsy surgery.
PMID- 25847678
TI - The topical treatment of anthroponotic cutaneous leishmaniasis with the tincture
of thioxolone plus benzoxonium chloride (Thio-Ben) along with cryotherapy: a
single-blind randomized clinical trial.
AB - A simple efficacious topical treatment for cutaneous leishmaniasis (CL) is still
an unresolved challenge. This study aimed to evaluate the efficacy of the topical
use of thioxolone plus benzoxonium chloride (Thio-Ben) tincture in combination
with cryotherapy in comparison with intralesional meglumine antimoniate
(Glucantime) along with cryotherapy in treating anthroponotic CL (ACL). The study
was conducted in Leishmaniasis Center in Dadbin Health Care Clinic, Kerman, Iran.
Sixty-four CL lesions were randomly assigned to receive Thio-Ben plus cryotherapy
(TC) (n = 32) or Glucantime plus cryotherapy (GC) (n = 32). Thio-Ben was used
topically every other day and Glucantime was used intralesionally once a week for
a maximum of 3 months. In both study groups, cryotherapy was administered using
liquid nitrogen once every 2 weeks. Of 64 recruited lesions, 47 lesions completed
the study protocol. Twenty lesions (91%) in TC group and 23 lesions (92%) in GC
group showed complete cure. TC group showed faster clinical response. Pain,
hypersensitivity reaction, dizziness, and nausea were only seen in GC group. This
study showed that the topical use of Thio-Ben combined with cryotherapy has a
good efficacy in treating ACL with the benefit that Thio-Ben has more patient
compliance and less side effects than intralesional Glucantime.
PMID- 25847680
TI - Heteroleptic bis(dipyrrinato)copper(II) and nickel(II) complexes.
AB - Heteroleptic bis(dipyrrinato)copper(II) and nickel(II) complexes are synthesized.
Their structures are determined by X-ray diffraction analysis, and their
properties are investigated by using cyclic voltammetry, chronocoulometry, and
UV/vis absorption spectroscopy.
PMID- 25847681
TI - High juvenile hormone titre and abdominal activation of JH signalling may induce
reproduction of termite neotenics.
AB - Termite castes are a key example of polyphenism, in which reproductive division
of labour is clearly seen in colonies. The reproductive castes in termites
include primary and neotenic reproductives; primary reproductives found a new
colony whereas neotenics succeed them in the reproductive role when the primary
reproductives die or become senescent. Neotenics usually differentiate from
nymphs or workers by developing functional gonads while retaining juvenile
characteristics; however, the developmental mechanism during neotenic
differentiation remains poorly understood. Juvenile hormone (JH) mediates a
number of aspects of developmental regulation in caste differentiation in
termites. In the present study we quantified JH titres in neotenic reproductives
of Reticulitermes speratus, and compared these with other developmental stages.
In addition, expression changes in JH signalling gene homologues (Methoprene
tolerant [Met], Kruppel-homolog1, Broad-Complex) in the head, thorax and abdomen
were investigated during neotenic differentiation. Finally, we examined the
function of Met in reproduction of neotenics by RNA interference (RNAi). Our
results showed that the JH titres of neotenics were significantly higher than
those of nymphs and workers. JH signalling genes were highly expressed in
neotenic abdomens, compared with those in workers and nymphs. Met RNAi resulted
in the inhibition of vitellogenin gene expression in newly moulted neotenics.
These results suggest that the fertility of neotenics might be controlled by a
large increase of JH titres and body-part-specific activation of JH signalling
pathways.
PMID- 25847682
TI - EuroSCORE is a predictor of postoperative pericardial effusion following heart
transplantation.
AB - BACKGROUND: Pericardial effusion is an early complication following orthotopic
heart transplantation. Effusion that requires surgical intervention not only
prolongs in-hospital stay but also increases early mortality rate. EuroSCORE is
one of the most common methods for calculating predictive mortality in heart
surgery. MATERIAL AND METHODS: We performed a retrospective analysis of 25
patients (22 men and 3 women, mean age 49+/-12 years). Mortality risk by
EuroSCORE was estimated prior to surgery. All patients were operated on with
Lower-Shumway technique and treated with standard triple immunosuppressive
regimen (tacrolimus, mycophenolate mofetil, and prednisolone). They were divided
into 2 groups depending on postoperative pericardial effusion that required
surgical intervention. There were 9 (36%) patients in the pericardial effusion
group (PE group) and 16 (64%) in the control group (C group). RESULTS: There was
1 death, on the 7th postoperative day, due to Clostridium difficile infection.
Mean time of pericardial effusion echocardiographic detection was 9+/-2 days
following surgery. The mean amount of fluid diagnosed in 4-chamber transthoracic
echocardiography was 2.2+/-0.3 cm vs. 0.7+/-0.2 cm (p<0.05). Pericardial effusion
followed thrombocytopenia of 98+/-17 vs. 172+/-26*109/L in PE and C group
(p<0.05). Patients' mean intensive care unit time stay was 23+/-9 days and 11+/-7
days in PE and C group, respectively (p<0.05). The overall hospitalization time
was 38+/-12 days and 31+/-23 days in PE and C group, respectively (p<0.05). The
discriminant analysis showed that EuroSCORE >16% is a single predicting variable
for postoperative pericardial effusion (AUC 0.946, CI: 0.76-0.99). CONCLUSIONS:
Pericardial effusion is a common (36%) complication following heart
transplantation. It requires surgical intervention and prolongs intensive care
unit stay and overall hospitalization. The discriminant analysis showed that the
EuroSCORE >16% is a single predicting variable for postoperative pericardial
effusion.
PMID- 25847684
TI - Normothermic liver preservation: a new paradigm?
AB - Despite increasing donor numbers, waiting lists and pre-transplant mortality
continue to grow in many countries. The number of donor organs suitable for liver
transplantation is restricted by cold preservation and ischemia-reperfusion
injury (IRI). Transplantation of marginal donor organs has led to renewed
interest in new techniques which have the potential to improve the quality of
preservation, assess the quality of the organ and allow repair of the donor organ
prior to transplantation. If successful, such techniques would not only improve
the outcome of currently transplanted marginal livers, but also increase the
donor pool. Experimental evidence suggests that preservation under near
physiological conditions of temperature and oxygenation abrogates IRI.
Normothermic perfusion maintains the organ in a physiological state, avoiding the
depletion of cellular energy and the accumulation of waste products, which occurs
with static cold storage. It enables viability assessment prior to
transplantation thereby reducing the risk of transplanting inherently marginal
organs. Here we review the use of normothermic machine perfusion as a means of
organ preservation.
PMID- 25847683
TI - Lipoprotein receptor-related protein 6 is required for parathyroid hormone
induced Sost suppression.
AB - Parathyroid hormone (PTH) suppresses the expression of the bone formation
inhibitor sclerostin (Sost) in osteocytes by inducing nuclear accumulation of
histone deacetylases (HDACs) to inhibit the myocyte enhancer factor 2 (MEF2)
dependent Sost bone enhancer. Previous studies revealed that lipoprotein receptor
related protein 6 (LRP6) mediates the intracellular signaling activation and the
anabolic bone effect of PTH. Here, we investigated whether LRP6 mediates the
inhibitory effect of PTH on Sost using an osteoblast-specific Lrp6-knockout (LRP6
KO) mouse model. An increased level of Sost mRNA expression was detected in femur
tissue from LRP6-KO mice, compared to wild-type littermates. The number of
osteocytes expressing sclerostin protein was also increased in bone tissue of
LRP6-KO littermates, indicating a negative regulatory role of LRP6 on
Sost/sclerostin. In wild-type littermates, intermittent PTH treatment
significantly suppressed Sost mRNA expression in bone and the number of
sclerostin(+) osteocytes, while the effect of PTH was much less significant in
LRP6-KO mice. Additionally, PTH-induced downregulation of MEF2C and 2D, as well
as HDAC changes in osteocytes, were abrogated in LRP6-KO mice. These data
indicate that LRP6 is required for PTH suppression of Sost expression.
PMID- 25847685
TI - Microtensile bond strength of a resin-based fissure sealant to Er,Cr:YSGG laser
etched primary enamel.
AB - The aim of this study was to evaluate the effect of Er,Cr:YSGG laser pre
treatment alone, or associated with acid-etching, on the microtensile bond
strength of a resin-based fissure sealant to primary enamel. Twenty-five human
primary molars were randomly divided into five groups including (1) 35 % acid
etching, (2) 2.5-W laser etching, (3) 3.5-W laser etching, (4) 2.5-W laser
etching + acid etching, and (5) 3.5-W laser etching + acid etching. Er,Cr:YSGG
laser was used at a wavelength of 2.780 nm and pulse duration of 140-200 MUs with
a repetition rate of 20 Hz. Following surface pre-treatment, the fissure sealant
(ClinProTM, 3M Dental Products) was applied. Each tooth was sectioned and
subjected to microtensile testing. Kruskal-Wallis test was used for statistical
analysis. The level of significance was set at p < 0.05. The microtensile bond
strength values of group 1 were significantly higher than those of group 2, while
no statistically significant difference was detected between groups 1, 3, 4, and
5. It was concluded that 3.5-W laser etching produced results comparable to
conventional acid etching technique, whereas 2.5-W laser etching was not able to
yield adequate bonding performance.
PMID- 25847688
TI - Fine-tuning of single-molecule conductance by tweaking both electronic structure
and conformation of side substituents.
AB - Herein, we describe a method to fine-tune the conductivity of single-molecule
wires by employing a combination of chemical composition and geometrical
modifications of multiple phenyl side groups as conductance modulators embedded
along the main axis of the electronic pathway. We have measured the single
molecule conductivity of a novel series of phenyl-substituted carotenoid wires
whose conductivity can be tuned with high precision over an order of magnitude
range by modulating both the electron-donating character of the phenyl
substituent and its dihedral angle. It is demonstrated that the electronic
communication between the phenyl side groups and the molecular wire is maximized
when the phenyl groups are twisted closer to the plane of the conjugated
molecular wire. These findings can be refined to a general technique for
precisely tuning the conductivity of molecular wires.
PMID- 25847687
TI - Enantioselective copper-catalyzed alkynylation of benzopyranyl oxocarbenium ions.
AB - We have developed highly enantioselective, copper-catalyzed alkynylations of
benzopyranyl acetals. By using a copper(I) catalyst equipped with a chiral
bis(oxazoline) ligand, high yields and enantioselectivities are achieved in the
alkynylation of widely available, racemic isochroman and chromene acetals to
deliver alpha-chiral oxygen heterocycles. This method demonstrates that chiral
organometallic nucleophiles can be successfully used in enantioselective
additions to oxocarbenium ions.
PMID- 25847686
TI - The primate amygdala in social perception - insights from electrophysiological
recordings and stimulation.
AB - The role of the amygdala in emotion and social perception has been intensively
investigated primarily through studies using functional magnetic resonance
imaging (fMRI). Recently, this topic has been examined using single-unit
recordings in both humans and monkeys, with a focus on face processing. The
findings provide novel insights, including several surprises: amygdala neurons
have very long response latencies, show highly nonlinear responses to whole
faces, and can be exquisitely selective for very specific parts of faces such as
the eyes. In humans, the responses of amygdala neurons correlate with internal
states evoked by faces, rather than with their objective features. Current and
future studies extend the investigations to psychiatric illnesses such as autism,
in which atypical face processing is a hallmark of social dysfunction.
PMID- 25847689
TI - So You Want to Be in Journals, or What Happens When You Press "Send".
PMID- 25847690
TI - Gastroretentive carbidopa/levodopa, DM-1992, for the treatment of advanced
Parkinson's disease.
AB - OBJECTIVES: This study was undertaken to compare efficacy, tolerability, and
pharmacokinetics of DM-1992, an extended-release formulation of
carbidopa/levodopa (CD/L-dopa) with immediate-release (IR) CD/L-dopa in patients
with advanced Parkinson's disease. METHODS: This randomized, open-label,
crossover study included a 3-d baseline and two 10-d treatment periods. Patients
with daily OFF time of 2.5 h or more taking 400 mg or more L-dopa/d in four or
more divided doses were titrated to stable regimens of DM-1992 2 times per day or
CD/L-dopa IR 3 times to 8 times per day. Patients were allowed to take rescue
CD/L-dopa as needed. Using home diaries, patients recorded OFF time and ON time
with or without troublesome dyskinesia during baseline and treatment days 7
through 9. During 12-h clinic visits on day 10, plasma samples were collected for
pharmacokinetics, and motor performance was assessed hourly. RESULTS: Thirty-four
patients were enrolled; mean baseline L-dopa dosage was 968 mg/d. After
titration, CD/L-dopa IR was dosed 4.8 times per day and DM-1992, 2 times per day.
Rescue CD/L-dopa IR was given 1.3 times during the DM-1992 arm and 0.2 times
during the CD/L-dopa IR arm. The reduction from baseline in % OFF time was
greater for DM-1992 compared with CD/L-dopa IR (-5.52% vs. +1.33%; P = 0.0471).
At steady-state, compared with CD/L-dopa IR, DM-1992 exhibited a smoother plasma
L-dopa concentration profile mostly because of a significantly higher (day 10)
predose L-dopa concentration, associated with enhanced motor performance.
Although more patients taking DM-1992 had one or more adverse events (AEs) than
CD/L-dopa IR patients (35% vs. 15%), no pattern to the AEs was seen, nor any
resulting discontinuations. CONCLUSIONS: DM-1992 was associated with a reduction
in %OFF time compared with CD/L-dopa IR despite a reduced dosing frequency.
Although the open-label study design and the greater number of rescue doses
during the DM-1992 arm call for caution in interpreting the results, the elevated
predose plasma L-dopa concentration (12 h after DM-1992 administration) lends
objective support to our findings, suggesting that phase 3 studies are warranted.
PMID- 25847691
TI - Fluorescence fingerprint as an instrumental assessment of the sensory quality of
tomato juices.
AB - BACKGROUND: Sensory analysis is an important standard for evaluating food
products. However, as trained panelists and time are required for the process,
the potential of using fluorescence fingerprint as a rapid instrumental method to
approximate sensory characteristics was explored in this study. RESULTS: Thirty
five out of 44 descriptive sensory attributes were found to show a significant
difference between samples (analysis of variance test). Principal component
analysis revealed that principal component 1 could capture 73.84 and 75.28%
variance for aroma category and combined flavor and taste category respectively.
Fluorescence fingerprints of tomato juices consisted of two visible peaks at
excitation/emission wavelengths of 290/350 and 315/425 nm and a long narrow
emission peak at 680 nm. The 680 nm peak was only clearly observed in juices
obtained from tomatoes cultivated to be eaten raw. The ability to predict overall
sensory profiles was investigated by using principal component 1 as a regression
target. Fluorescence fingerprint could predict principal component 1 of both
aroma and combined flavor and taste with a coefficient of determination above
0.8. CONCLUSION: The results obtained in this study indicate the potential of
using fluorescence fingerprint as an instrumental method for assessing sensory
characteristics of tomato juices.
PMID- 25847692
TI - Integration analysis of miRNA and mRNA expression profiles in swine testis cells
infected with Japanese encephalitis virus.
AB - To elucidate the role of microRNAs (miRNA) in the regulation of gene expression
in Japanese encephalitis virus (JEV) infected swine testis (ST) cells, we
analyzed miRNA and mRNA expression profiles of JEV infected ST cells by high
throughput sequencing technology as compared to uninfected controls. The results
showed that 104 known miRNAs and 9 new miRNA candidates were differentially
expressed in ST cells after JEV infection. We identified 396 differentially
expressed mRNAs. Bioinformatics analysis identified 435 known miRNA-mRNA
interaction pairs and 94 novel miRNA-mRNA interaction pairs involving miRNAs
inversely correlated with the expression of their predicted target mRNAs. The
known miRNAs inversely correlated with their target genes were involved in the
biological processes of immunity, cytokine production, inflammation, and
apoptosis. Selected miRNA-mRNA interactions were validated by luciferase reporter
assay. Overall, our findings indicate that miRNAs may play critical roles in the
pathogenesis of JEV infection.
PMID- 25847693
TI - Inflammasome signaling pathways exert antiviral effect against Chikungunya virus
in human dermal fibroblasts.
AB - Arboviruses represent an emerging threat to human. They are transmitted to
vertebrates by the bite of infected arthropods. Early transmission to vertebrates
is initiated by skin puncture and deposition of virus in this organ. However,
events at the bite site remain largely unknown. Here, we report that Chikungunya
virus (CHIKV) and West Nile virus (WNV), despite belonging to distinct viral
families, elicit a common antiviral signature in primary human dermal
fibroblasts, attesting for the up regulation of interferon signaling pathways and
leading to an increased expression of IFN-beta, interleukins and chemokines.
Remarkably, CHIKV and WNV enhance IL-1beta expression and induce maturation of
caspase-1, indicating the capacity of these pathogens to elicit activation of the
inflammasome program in resident skin cells. CHIKV and WNV also induce the
expression of the inflammasome sensor AIM2 in dermal fibroblasts, whereas
inhibition of caspase-1 and AIM2 with siRNA interferes with both CHIKV- and WNV
induced IL-1beta production by these cells. Finally, inhibition of the
inflammasome via caspase-1 silencing was found to enhance CHIKV replication in
dermal fibroblasts. Together, these results indicate that the skin contributes to
the pro-inflammatory and anti-viral microenvironment via the activation of the
inflammasome in the early stages following infection with arboviruses.
PMID- 25847694
TI - Molecular characterization and genetic susceptibility of sapovirus in children
with diarrhea in Burkina Faso.
AB - Sapoviruses (SaVs) are a common cause of gastroenteritis in children. In sub
Saharan Africa, there is a scarcity of information regarding SaV as an
etiological agent of diarrhea. Here, we investigated the prevalence, molecular
characterization and clinico-epidemiological features of SaV infections in
children less than 5years of age with diarrhea in Burkina Faso. We further
investigated the role of type 1 histo blood group antigens as susceptibility
factors. In total, 309 fecal and 208 saliva samples from diarrheal children in
Ouagadougou, Burkina Faso, were collected between May 2009 and March 2010. SaV
was detected using real-time PCR, and genogrouped/genotyped by PCR or sequencing.
Saliva samples were ABO, Lewis and secretor phenotyped using in house ELISA
assays. We found a high prevalence (18%) and large genetic diversity with all 4
human genogroups, and 9 genotypes/genoclusters circulating during the study
period. The SaV infections were generally associated with milder symptoms, and
neither ABH, Lewis or secretor phenotypes affected susceptibility to SaV
infections.
PMID- 25847695
TI - Emergence of multireassortant bluetongue virus serotype 4 in Hungary.
AB - The genome sequence and the phylogenetic relationships of a serotype 4 bluetongue
virus (BTV-4) emerged during 2014 in Hungary are described in this study. Genome
segment 2 encoding the major neutralization antigen, VP2, shared moderate
sequence similarity (nt, ? 94.3%) with the corresponding gene of contemporary and
historic homotypic bluetongue viruses, whereas genome segments S1, S4, S5, S7-S10
were typically more closely related to the cognate genes of heterotypic isolates.
Importantly, in many gene phylogenies the Hungarian BTV-4 strain showed genetic
relationship to BTV strains identified in outbreaks in the western Mediterranean
basin. Our results indicate the identified Hungarian bluetongue virus strain
evolved through reassortment involving multiple genome segments from various
heterotypic bluetongue viruses.
PMID- 25847696
TI - Intrasegmental recombination does not contribute to the long-term evolution of
group A rotavirus.
AB - Rotavirus is a genetically diverse pathogen with an eleven-segmented, double
stranded RNA genome. Intrasegmental recombination has been proposed as a
potential mechanism to generate antigenic diversity and a possible route of
escape from vaccine-imposed selective pressure. Here intrasegmental recombination
was studied by performing a genome-wide scan across the eleven genome segments of
797 publically available rotavirus strains. Sixty-two sequences, or 0.7% of
sequences analyzed, have evidence of intrasegmental homologous recombination.
None of the specific recombination events is seen in more than one sequence. This
uniqueness is consistent with either a spurious finding of recombination or the
possibility that recombinant sequences arise naturally but are rapidly purged
from the rotavirus population through selection. Arguments for the former
explanation are presented. This analysis finds no evidence that intrasegmental
recombination leads to ongoing transmission or plays a constructive role in
rotavirus evolution. These results have practical implications for phylogenetic
analyses and suggest a fundamental constraint that may have shaped rotavirus
genome structure and evolution.
PMID- 25847697
TI - Genomic characterization of EmsB microsatellite loci in Echinococcus
multilocularis.
AB - EmsB is a molecular marker applied to Echinococcus multilocularis genotyping
studies. This marker has largely been used to investigate the epidemiology of the
parasite in different endemic foci. The present study has lifted the veil on the
genetic structure of this microsatellite. By in silico analysis on the E.
multilocularis genome the microsatellite was described in about 40 copies on the
chromosome 5 of the parasite. Similar structure was found in the relative
parasite Echinococcus granulosus, where the microsatellite was firstly described.
The present study completes the first investigations made on the EmsB
microsatellite origins and confirms the reliability of this highly discriminant
molecular marker.
PMID- 25847698
TI - Genotypic diversity of multidrug-, quinolone- and extensively drug-resistant
Mycobacterium tuberculosis isolates in Thailand.
AB - Drug-resistant tuberculosis (TB), which includes multidrug-resistant (MDR-TB),
quinolone-resistant (QR-TB) and extensively drug-resistant tuberculosis (XDR-TB),
is a serious threat to TB control. We aimed to characterize the genotypic
diversity of drug-resistant TB clinical isolates collected in Thailand to
establish whether the emergence of drug-resistant TB is attributable to
transmitted resistance or acquired resistance. We constructed the first molecular
phylogeny of MDR-TB (n=95), QR-TB (n=69) and XDR-TB (n=28) in Thailand based on
spoligotyping and proposed 24-locus multilocus variable-number of tandem repeat
analysis (MLVA). Clustering analysis was performed using the unweighted pair
group method with arithmetic mean. Spoligotyping identified the Beijing strain
(SIT1) as the most predominant genotype (n=139; 72.4%). The discriminatory power
of 0.9235 Hunter-Gaston Discriminatory Index (HGDI) with the 15-locus variable
number tandem repeats of mycobacterial interspersed repetitive units typing was
improved to a 0.9574 HGDI with proposed 24-locus MLVA, thereby resulting in the
subdivision of a large cluster of Beijing strains (SIT1) into 17 subclusters. We
identified the spread of drug-resistant TB clones caused by three different MLVA
types in the Beijing strain (SIT1) and a specific clone of XDR-TB caused by a
rare genotype, the Manu-ancestor strain (SIT523). Overall, 49.5% of all isolates
were clustered. These findings suggest that a remarkable transmission of drug
resistant TB occurred in Thailand. The remaining 50% of drug-resistant TB
isolates were unique genotypes, which may have arisen from the individual
acquisition of drug resistance. Our results suggest that transmitted and acquired
resistance have played an equal role in the emergence of drug-resistant TB.
Further characterization of whole genome sequences of clonal strains could help
to elucidate the mycobacterial genetic factors relevant for drug resistance,
transmissibility and virulence.
PMID- 25847699
TI - Comparative effectiveness of surgery and radiosurgery for stage I non-small cell
lung cancer.
AB - BACKGROUND: Although surgery is the standard treatment for early-stage non-small
cell lung cancer (NSCLC), stereotactic body radiotherapy (SBRT) has been
disseminated as an alternative therapy. The comparative mortalities and
toxicities of these treatments for patients of different life expectancies are
unknown. METHODS: The Surveillance, Epidemiology, and End Results-Medicare linked
database was used to identify patients who were 67 years old or older and
underwent SBRT or surgery for stage I NSCLC from 2007 to 2009. Matched patients
were stratified into short life expectancies (<5 years) and long life
expectancies (>=5 years). Mortality and complication rates were compared with
Poisson regression. RESULTS: Overall, 367 SBRT patients and 711 surgery patients
were matched. Acute toxicity (0-1 month) was lower from SBRT versus surgery (7.9%
vs 54.9%, P < .001). At 24 months after treatment, there was no difference (69.7%
vs 73.9%, P = .31). The incidence rate ratio (IRR) for toxicity from SBRT versus
surgery was 0.74 (95% confidence interval [CI], 0.64-0.87). Overall mortality was
lower with SBRT versus surgery at 3 months (2.2% vs 6.1%, P = .005), but by 24
months, overall mortality was higher with SBRT (40.1% vs 22.3%, P < .001). For
patients with short life expectancies, there was no difference in lung cancer
mortality (IRR, 1.01; 95% CI, 0.40-2.56). However, for patients with long life
expectancies, there was greater overall mortality (IRR, 1.49; 95% CI, 1.11-2.01)
as well as a trend toward greater lung cancer mortality (IRR, 1.63; 95% CI, 0.95
2.79) with SBRT versus surgery. CONCLUSIONS: SBRT was associated with lower
immediate mortality and toxicity in comparison with surgery. However, for
patients with long life expectancies, there appears to be a relative benefit from
surgery versus SBRT.
PMID- 25847700
TI - Genomewide analysis of phytochrome proteins in the phylum Basidiomycota.
AB - Phytochromes are photoreceptor proteins involved in the detection of the red and
far-red regions of the visible light spectrum. Fungal phytochromes are hybrid
histidine kinases with a conserved domain architecture composed of an N-terminal
photosensory module and a C-terminal regulatory output module that includes the
histidine kinase and response regulator receiver domains. In this study, we have
analyzed the distribution, domain architecture, and phylogenetic analysis of
phytochrome proteins in 47 published genome sequences among the phylum
Basidiomycota. Genome analysis revealed that almost every genome of
basidiomycetes contained at least one gene encoding a phytochrome protein. Domain
architecture of fungal phytochromes was completely conserved in the identified
phytochromes of basidiomycetes, and phylogenetic analysis clustered these
proteins into clades related with the phylogenetic classification of this fungal
phylum.
PMID- 25847701
TI - One-Pot Preparation of Inert Well-Defined Polymers by RAFT Polymerization and In
Situ End Group Transformation.
AB - A one-pot procedure that straightforwardly combines reversible addition
fragmentation chain transfer (RAFT) polymerization and end group transformation
to remove the RAFT end groups is developed for the synthesis of well-defined
poly(meth)acrylates and polyacrylamides with inert end groups. This procedure
only requires the addition of an amine at the end of the standard RAFT
polymerization procedure, which avoids the separation and purification of the
intermediate polymers and, hence, extremely reduces the working time and utilized
amount of solvents. Upon addition of the amine, a thiol group is formed by
aminolysis of the thiocarbonylthio group, which subsequently undergoes Michael
addition with unreacted monomer leading to an inert thioether functionalized
polymer.
PMID- 25847703
TI - Using bonding to guide transition state optimization.
AB - Optimization of a transition state typically requires both a good initial guess
of the molecular structure and one or more computationally demanding Hessian
calculations to converge reliably. Often, the transition state being optimized
corresponds to the barrier in a chemical reaction where bonds are being broken
and formed. Utilizing the geometries and bonding information for reactants and
products, an algorithm is outlined to reliably interpolate an initial guess for
the transition state geometry. Additionally, the change in bonding is also used
to increase the reliability of transition state optimizations that utilize
approximate and updated Hessian information. These methods are described and
compared against standard transition state optimization methods.
PMID- 25847702
TI - Validation and cross-cultural adaptation of the 'Fibromyalgia Participation
Questionnaire' to the Spanish population: study protocol.
AB - There are few high-quality instruments to evaluate the participation and social
functioning of fibromyalgia patients. The Fibromyalgia Participation
Questionnaire (FPQ) is a questionnaire that evaluates these aspects with high
reliability and validity in its German original version. The aim of this work was
to describe the translation and cross-cultural adaptation process of the FPQ into
Spanish and its validation to ensure the equivalence against the original
version. The questionnaire will be translated according to the FACIT methodology,
and it will be tested in the Clinical Management Unit of North Almeria Health
Area. This methodology includes several stages: double forward translation,
reconciled version, back-translation, review of the previous versions and
development of the prefinal version for the pretest. Once the pretest ends, the
final version of the questionnaire will be developed, which will be subjected to
a validation process to study its psychometric properties. Reliability will be
studied by internal consistency and test-retest reliability through Cronbach's
alpha and Pearson's correlation coefficient, respectively. External and construct
validity will be analysed using correlation coefficients, content validity with
an empirical analysis, and a differential item functioning analysis will be
employed to measure discriminative validity. The presence of ceiling and floor
effects will be calculated too. The validation of the FPQ into different
languages will allow better evaluation and treatment based on the observed
limitations fibromyalgia patients suffer from, as well as bringing the
possibility to compare between other countries and generalize its use in the
scientific community.
PMID- 25847704
TI - High diagnostic accuracy of the Sysmex XT-2000iV delta total nucleated cells on
effusions for feline infectious peritonitis.
AB - BACKGROUND: The DeltaWBC (the ratio between DIFF and BASO counts of the Sysmex XT
2000iV), hereafter defined as DeltaTNC (total nucleated cells), is high in
effusions due to feline infectious peritonitis (FIP), as cells are entrapped in
fibrin clots formed in the BASO reagent. Similar clots form in the Rivalta's
test, a method with high diagnostic accuracy for FIP. OBJECTIVES: The objective
of this study was to determine the diagnostic accuracy for FIP and the optimal
cutoff of DeltaTNC. METHODS: After a retrospective search of our database, DIFF
and BASO counts, and the DeltaTNC from cats with and without FIP were compared to
each other. Sensitivity, specificity, and positive and negative likelihood ratios
(LR+, LR-) were calculated. A ROC curve was designed to determine the cutoff for
best sensitivity and specificity. RESULTS: Effusions from 20 FIP and 31 non-FIP
cats were analyzed. The DeltaTNC was higher (P < .001), and BASO and DIFF counts
were lower (P < .001 and P < .05) in FIP than in non-FIP cats. Only 2 FIP cats
with atypical effusions had a DeltaTNC < 3.0. The cutoff identified by the ROC
curve (area under curve: 0.94; P < .001) was 1.7 (Sensitivity = 90.0%;
Specificity = 93.53%; LR+ = 13.9; LR- = 0.1). A DeltaTNC > 2.5 had 100%
specificity. CONCLUSIONS: The DeltaTNC has a high diagnostic accuracy for FIP
related effusions by providing an estimate of precipitable proteins, as the
Rivalta's test, in addition to the cell count. As fibrin clots result in false
lower BASO counts, the DeltaTNC is preferable to the WBC count generated by the
BASO channel alone in suspected FIP effusions.
PMID- 25847706
TI - Genetic admixture supports an ancient hybrid origin of the endangered Hawaiian
duck.
AB - Speciation is regarded primarily as a bifurcation from an ancestral species into
two distinct taxonomic units, but gene flow can create complex signals of
phylogenetic relationships, especially among different loci. We evaluated several
hypotheses that could account for phylogenetic discord between mitochondrial DNA
(mtDNA) and nuclear DNA (nuDNA) within Hawaiian duck (Anas wyvilliana), including
stochastic lineage sorting, mtDNA capture and widespread genomic introgression.
Our results best support the hypothesis that the contemporary Hawaiian duck is
descended from an ancient hybridization event between the mallard (Anas
platyrhynchos) and Laysan duck (Anas laysanensis). Whereas mtDNA clearly shows a
sister relationship between Hawaiian duck and mallard, nuDNA is consistent with a
genetic mosaic with nearly equal contributions from Laysan duck and mallard. In
addition, coalescent analyses suggest that gene flow from either mallard or
Laysan duck, depending on the predefined tree topology, is necessary to explain
contemporary genetic diversity in Hawaiian ducks, and these estimates are more
consistent with ancient, rather than contemporary, hybridization. Time since
divergence estimates suggest that the genetic admixture event occurred around the
Pleistocene-Holocene boundary, which is further supported by circumstantial
evidence from the Hawaiian subfossil record. Although the extent of reproductive
isolation from either putative parental taxon is not currently known, these
species are phenotypically, genetically and ecologically different, and they meet
primary criteria used in avian taxonomy for species designation. Thus, the
available data are consistent with an admixed origin and support the hypothesis
that the Hawaiian duck may represent a young hybrid species.
PMID- 25847705
TI - The ACVRL1 c.314-35A>G polymorphism is associated with organ vascular
malformations in hereditary hemorrhagic telangiectasia patients with ENG
mutations, but not in patients with ACVRL1 mutations.
AB - Hereditary hemorrhagic telangiectasia (HHT) is characterized by vascular
malformations (VMs) and caused by mutations in TGFbeta/BMP9 pathway genes, most
commonly ENG or ACVRL1. Patients with HHT have diverse manifestations related to
skin and mucosal telangiectases and organ VMs, including arteriovenous
malformations (AVM). The clinical heterogeneity of HHT suggests a role for
genetic modifiers. We hypothesized that the ACVRL1 c.314-35A>G and ENG c.207G>A
polymorphisms, previously associated with sporadic brain AVM, are associated with
organ VM in HHT. We genotyped these variants in 716 patients with HHT and
evaluated association of genotype with presence of any organ VM, and specifically
with brain VM, liver VM and pulmonary AVM, by multivariate logistic regression
analyses stratified by HHT mutation. Among all patients with HHT, neither
polymorphism was significantly associated with presence of any organ VM; ACVRL1
c.314-35A>G showed a trend toward association with pulmonary AVM (OR = 1.48, P =
0.062). ACVRL1 c.314-35A>G was significantly associated with any VM among
patients with HHT with ENG (OR = 2.66, P = 0.022), but not ACVRL1 (OR = 0.79, P =
0.52) mutations. ACVRL1 c.314-35A>G was also associated with pulmonary AVM and
liver VM among ENG mutation heterozygotes. There were no significant associations
between ENG c.207G>A and any VM phenotype. These results suggest that common
polymorphisms in HHT genes other than the mutated gene modulate phenotype
severity of HHT disease, specifically presence of organ VM.
PMID- 25847707
TI - Prevalence of Baseline Erectile Dysfunction (ED) in an Australian Cohort of Men
with Localized Prostate Cancer.
AB - INTRODUCTION: Erectile dysfunction (ED) is a common complication following
prostate cancer treatment. Post-treatment erectile function (EF) preservation is
strongly dependent on the baseline EF prior to treatment. AIM: To assess the
baseline EF among patients with localized prostate cancer, and the factors
associated with baseline EF. METHODS: All men with clinically localized prostate
cancer had their baseline EF assessed prior to brachytherapy at our institution.
Six hundred ninety-nine men who completed the International Index of Erectile
Function five-item questionnaires pre-treatment between 2001 and 2013 were
included in the study. Data on patient factors (medical comorbidities and smoking
history) and prostate cancer clinicopathological characteristics were recorded.
Ordinal logistic regressions were used to estimate the effects of each variable
on the severity of ED. MAIN OUTCOME MEASURES: Baseline EF among men with
localized prostate cancer, and factors associated with ED. RESULTS: Prior to
permanent seed brachytherapy, 335 (48%) patients reported no ED, 129 (17%) mild
ED, 42 (6%) mild-moderate ED, 37 (5%) moderate ED, and 165 (24%) severe ED. In
multivariate analyses, age, diabetes, and hypertension remained to be
independently associated with ED, with diabetes most strongly associated with
worse ED (odds ratio = 2.6; 95% confidence interval = 1.3-5.3). CONCLUSIONS: ED
is common among patients with localized prostate cancer prior to any curative
treatment. Assessment of baseline ED is important prior to curative treatment of
prostate cancer in order to offer appropriate advise on likelihood of EF
preservation post-treatment and avoid patient dissatisfaction with treatment
outcomes due to unrealistic expectations.
PMID- 25847715
TI - Intraocular BDNF promotes ectopic branching, alters motility and stimulates
abnormal collaterals in regenerating optic fibers.
AB - A great deal of effort has been invested in using trophic factors and other
bioactive molecules to promote cell survival and axonal regeneration in the adult
central nervous system. Far less attention has been paid to investigating
potential effects that trophic factors may have that might interfere with
recovery. In the visual system, BDNF has been previously reported to prevent
regeneration. To test if BDNF is inherently incompatible with regeneration, BDNF
was given intraocularly during optic nerve regeneration in the adult goldfish. In
vivo imaging and anatomical analysis of selectively labeled axons were used as a
sensitive assay for effects on regeneration within the tectum. BDNF had no
detectable inhibitory effect on the ability of axons to regenerate. Normal
numbers of axons regenerated into the tectum, exhibited dynamic growth and
retractions similar to controls, and were able to navigate to their correct
target zone in the tectum. However, BDNF was found to have additional effects
that adversely affected the quality of regeneration. It promoted premature
branching at ectopic locations, diminished the growth rate of axons through the
tectum, and resulted in the formation of ectopic collaterals. Thus, although BDNF
has robust effects on axonal behavior, it is, nevertheless, compatible with
axonal regeneration, axon navigation and the formation of terminal arbors.
PMID- 25847716
TI - Differential regulation of HIF-3alpha in LPS-induced BV-2 microglial cells:
Comparison and characterization with HIF-1alpha.
AB - Hypoxia inducible factor(s) (HIF) are transcription factors that respond to a low
level of oxygen or hypoxic conditions. The HIF pathway has been poorly studied
under neuroinflammatory conditions, and no reports are available on the
regulation of HIF-3alpha. Several studies have established that non-hypoxic
stimuli can modulate the HIF pathway in a cell-specific manner. Recent reports
suggest that hypoxia elicits inflammation or that inflammation during hypoxia is
involved in a wide array of human diseases. In the present study, we used
lipopolysaccharide (LPS), a well know inflammatory agent, to characterize the HIF
3alpha expression pattern and compare it with that of HIF-1alpha under
inflammatory conditions in BV-2 microglial cells. Moreover, we used reactive
oxygen species inhibitors (rotenone, diphenyleneiodonium, and N-acetyl-L
cysteine) under inflammatory conditions to determine the role of the functional
electron transport chain in the regulation of HIF-3alpha in BV-2 microglial
cells. Additionally, we utilized YC-1, a specific inhibitor of HIF-1alpha, to
determine the role of HIF-3alpha in inflammatory conditions after inhibiting the
HIF-1alpha pathway. YC-1 inhibited nuclear localization of HIF-1alpha following
treatment with LPS in BV-2 microglia cells. Immunoblot and immunocytochemistry
revealed a transient effect on HIF-3alpha after pre-treating the cells with YC-1.
Furthermore, we determined the role of nuclear factor kappa B (NF-kappaB) in the
regulation of HIF-3alpha using the NF-kappaB inhibitor PDTC in LPS-stimulated BV
2 microglia cells. PDTC altogether abolished LPS-induced nuclear translocation of
HIF-3alpha with a partial effect on HIF-1alpha, suggesting that HIF-3alpha
expression under inflammatory conditions may be directly under the control of the
NF-kappaB pathway in BV-2 microglial cells. Interestingly, HIF-3alpha and HIF
1alpha exhibited almost similar responses to a variety of activating or
inhibiting pharmacological agents. These results provide the first evidence for
regulation of HIF-3alpha under inflammatory conditions in BV-2 microglial cells.
PMID- 25847717
TI - Brain mechanisms of pain relief by transcutaneous electrical nerve stimulation: A
functional magnetic resonance imaging study.
AB - BACKGROUND: Although the exact mechanism of TENS pain relief is unknown, it is
believed that TENS impulses interrupt nociceptive signals at the dorsal horn of
the spinal cord. AIMS: To evaluate the hypotheses that during pain caused by
noxious stimuli, brain responses, temporal summation and brain functional
connectivity are modulated by TENS, and that mechanisms of pain relief by TENS
differ between men and women. METHODS: During fMRI scanning, the same noxious
stimuli were delivered to each participant in pain-only and pain+TENS conditions.
In the pain-only condition, noxious stimuli were presented without TENS. In the
pain+TENS condition, participants received noxious stimuli and TENS concurrently.
Participants were initially presented with TENS at an intensity that was just
below that causing discomfort. TENS intensity was presented in a step-wise
fashion to prevent temporal summation from repetitive noxious stimuli. RESULTS:
Pain and unpleasantness ratings were significantly higher in the pain-only than
the pain+TENS condition. With non-painful TENS, primary and secondary
somatosensory and parietal cortices were activated, and temporal summation from
repetitive noxious stimuli was prevented. Periaqueductal gray (PAG) and lateral
prefrontal cortex functional connectivity was increased by TENS, and modulated by
testosterone and cortisol. Women reported greater pain during TENS than men, and
showed greater activation in the temporoparietal junction cortex and increased
PAG functional connectivity with the orbitofrontal cortex. CONCLUSION: TENS led
to pain reduction, probably due to activation of the descending pain-inhibitory
pathway, indicating that this TENS method may be applied in clinical practice.
PMID- 25847718
TI - Ten years of science news: A longitudinal analysis of scientific culture in the
Spanish digital press.
AB - This article presents our study of science coverage in the digital Spanish press
over the last decade. We employed automated information retrieval procedures to
create a corpus of 50,763 text units dealing with science and technology, and
used automated text-analysis procedures in order to provide a general picture of
the structure, characteristics and evolution of science news in Spain. We found
between 6% and 7% of science coverage, a clear high proportion of biomedicine and
predominance of science over technology, although we also detected an increase in
technological content during the second half of the decade. Analysing the
extrinsic and intrinsic features of science culture, we found a predominance of
intrinsic features that still need further analysis. Our attempt to use
specialised software to examine big data was effective, and allowed us to reach
these preliminary conclusions.
PMID- 25847719
TI - How certain is 'certain'? Exploring how the English-language media reported the
use of calibrated language in the Intergovernmental Panel on Climate Change's
Fifth Assessment Report.
AB - This article presents findings from an analysis of English-language media reports
following the publication of the fifth Intergovernmental Panel on Climate Change
Assessment Report in September 2013. Focusing on the way they reported the
Intergovernmental Panel on Climate Change's use of 'calibrated' language, we find
that of 1906 articles relating to the issuing of the report only 272 articles
(14.27%) convey the use of a deliberate and systematic verbal scale. The
Intergovernmental Panel on Climate Change's carefully calibrated language was
rarely discussed or explicated, but in some instances scientists, political
actors or journalists would attempt to contextualise or elaborate on the reported
findings by using analogies to other scientific principles or examples of taking
action despite uncertainty. We consider those analogies in terms of their
efficacy in communicating (un)certainty.
PMID- 25847720
TI - EPSPS gene amplification in glyphosate-resistant Bromus diandrus.
AB - BACKGROUND: Glyphosate is the most widely used herbicide in the world and has
been intensively used to control B. diandrus, a problematic weed of crops and
pastures in southern Australia. RESULTS: Resistance to glyphosate was identified
in two populations of B. diandrus that were nearly fivefold more resistant to
glyphosate than wild-type plants. Both populations contained EPSPS gene
amplification, with resistant plants having an average of around 20-fold the
number of copies of EPSPS compared with susceptible plants. EPSPS expression was
also increased in resistant plants of both populations; however, expression
levels were not correlated with the number of EPSPS copies. Amplification of only
one of the four EPSPS genes present in B. diandus was detected. Investigation
into the inheritance of glyphosate resistance found no segregation in the F2
generation. Every individual in the F2 populations contained between three and 30
copies of EPSPS; however, on average they contained fewer copies compared with
the parent resistant population. CONCLUSIONS: Glyphosate resistance in B.
diandrus is due to EPSPS gene amplification. Resistance is heritable but complex.
PMID- 25847721
TI - Clinical outcomes and histological findings of patients with advanced metastatic
germ cell tumors undergoing post-chemotherapy resection of retroperitoneal lymph
nodes and residual extraretroperitoneal masses.
AB - OBJECTIVES: To assess clinical outcomes of patients with advanced germ cell tumor
undergoing post-chemotherapy retroperitoneal lymph node dissection with or
without extraretroperitoneal mass resection. METHODS: Between 1998 and 2013, 175
retroperitoneal lymph node dissections for advanced metastatic germ cell tumors
were carried out at Kyoto Prefectural University of Medicine, Kyoto, Japan. Of
patients receiving retroperitoneal lymph node dissections, 156 underwent post
chemotherapy retroperitoneal lymph node dissection with or without
extraretroperitoneal mass resection as first surgery after completion of
chemotherapy. Of these 156 patients, 47 underwent both post-chemotherapy
retroperitoneal lymph node dissection and extraretroperitoneal mass resection.
RESULTS: The histological findings were necrosis in 59.6%, teratoma in 31.4% and
viable cancer in 9.0% at retroperitoneal lymph node. At extraretroperitoneal mass
resection, necrosis was present in 59.6%, teratoma in 31.9% and viable cancer in
8.5%. Overall histological discordance between retroperitoneal lymph node and
extraretroperitoneal mass was found in 31.9%. Five-year disease-free survival
stratified by retroperitoneal lymph node histology in 156 patients was 91.3% for
necrosis, 78.7% for teratoma and 63.5% for viable cancer (log-rank, P = 0.009).
Antegrade ejaculation was preserved in 80.9%. In the worst histology of post
chemotherapy retroperitoneal lymph node dissection or extraretroperitoneal mass
resection in 156 patients, 5-year disease-free survival was 93.2% for necrosis,
79.0% for teratoma and 63.4% for viable cancer (log-rank, P < 0.001). Independent
prognostic factors for disease-free survival were presence of viable cancer in
retroperitoneal lymph node histology and salvage chemotherapy. CONCLUSION: The
presence of viable cancer at the retroperitoneal lymph node is an independent
predictor of disease recurrence. In approximately one-third of cases, there is a
histological discordance between retroperitoneal lymph node and
extraretroperitoneal mass. Resection of residual retroperitoneal lymph node and
extraretroperitoneal masses remains an important procedure in the management of
advanced germ cell tumors.
PMID- 25847722
TI - Comparison of the clinical and functional outcomes following 3- and 4-corner
fusions.
AB - PURPOSE: To explore the clinical and functional outcomes of 3-corner fusion (3CF)
for stage 2 and 3 scapholunate advanced collapse and scaphoid nonunion advanced
collapse. We compared the results with 4-corner fusion (4CF) using a recent
published report. METHODS: Twelve patients (8 men and 4 women) who had a 3CF,
mean age 60 years (range, 34-75 y) were reviewed in clinic more than 1 year after
surgery. Subjective outcome measures included the Michigan Hand Questionnaire and
Patient Evaluation Measure. Objective outcome measures included range of motion
with a flexible electrogoniometer and grip strength measured with a digital
dynamometer. The results were compared using a recent report of 24 patients (17
men and 7 women) with a 4CF, mean age 55 years (range, 34-68 y) assessed with
similar techniques. RESULTS: The patients receiving 3CF had better subjective
scores with the Michigan Hand Questionnaire, including the sub-scores for
activities of daily living and satisfaction. The radioulnar arc was greater after
the 3CF than after the 4CF. Circumduction of the 3CF was more like a normal wrist
than the 4CF. This included having faster and smoother motion, with an axis of
circumduction closer to the normal wrist. Peak grip strength was similar after
either a 3CF or 4CF but grip strength in the 3CF was 82% of the contralateral
wrist compared with 59% for the 4CF. CONCLUSIONS: The 3CF provided better patient
rated scores and the arc of wrist motion was more extended, with greater ulnar
deviation. Motion was smoother and more closely replicated the normal axis and
functional motion of the wrist. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.
PMID- 25847723
TI - Contributions of muscle imbalance and impaired growth to postural and osseous
shoulder deformity following brachial plexus birth palsy: a computational
simulation analysis.
AB - PURPOSE: Two potential mechanisms leading to postural and osseous shoulder
deformity after brachial plexus birth palsy are muscle imbalance between
functioning internal rotators and paralyzed external rotators and impaired
longitudinal growth of paralyzed muscles. Our goal was to evaluate the combined
and isolated effects of these 2 mechanisms on transverse plane shoulder forces
using a computational model of C5-6 brachial plexus injury. METHODS: We modeled a
C5-6 injury using a computational musculoskeletal upper limb model. Muscles
expected to be denervated by C5-6 injury were classified as affected, with the
remaining shoulder muscles classified as unaffected. To model muscle imbalance,
affected muscles were given no resting tone whereas unaffected muscles were given
resting tone at 30% of maximal activation. To model impaired growth, affected
muscles were reduced in length by 30% compared with normal whereas unaffected
muscles remained normal in length. Four scenarios were simulated: normal, muscle
imbalance only, impaired growth only, and both muscle imbalance and impaired
growth. Passive shoulder rotation range of motion and glenohumeral joint reaction
forces were evaluated to assess postural and osseous deformity. RESULTS: All
impaired scenarios exhibited restricted range of motion and increased and
posteriorly directed compressive glenohumeral joint forces. Individually,
impaired muscle growth caused worse restriction in range of motion and higher and
more posteriorly directed glenohumeral forces than did muscle imbalance. Combined
muscle imbalance and impaired growth caused the most restricted joint range of
motion and the highest joint reaction force of all scenarios. CONCLUSIONS: Both
muscle imbalance and impaired longitudinal growth contributed to range of motion
and force changes consistent with clinically observed deformity, although the
most substantial effects resulted from impaired muscle growth. CLINICAL
RELEVANCE: Simulations suggest that treatment strategies emphasizing treatment of
impaired longitudinal growth are warranted for reducing deformity after brachial
plexus birth palsy.
PMID- 25847724
TI - The validity and acceptability of a text-based monitoring system for pediatric
asthma studies.
AB - A meaningful analysis in research requires robust, valid data. Paper diaries
allow the collection of data from individuals over time but are notorious for
poor compliance and validity. SMS-technology is a novel method for data
collection in medical research. Time-tagged SMS are transferred directly to an
electronic file. We used SMS to collect symptoms and peak flow rate (PEFR) meter
readings from 32 children with asthma. Parents responded first to five SMS daily
for 7 days during an asymptomatic period and then for 14 days during a cold.
Compliance with use of PEFR meter and SMS system were assessed. Digital PEFR
meters enabled data download at the end of the study to confirm validity of
transmitted data. Parents of 24 participants provided feedback about this data
collection tool. Mean (+/-SD) "SMS-diary and PEFR-meter compliance" were 96% (+/
8) and 84% (+/-21) during baseline and 91% (+/-12) and 82% (+/-20) during cold
respectively. Correctly reported PEFR values were found in 65.5% of all cases, in
8.3% PEFR values sent were "self-invented" and 2.4% of values were missing. All
of the 22 parents completing the baseline questionnaire were happy to use SMS for
this study. Of the 20 parents completing the follow up questionnaire, 95% (19/20)
found the system user-friendly, 55% (11/20) would be more likely to participate
in studies if they were using SMS data collection and 25% (5/20) were "sometimes
unhappy" about receiving messages. This real-time capture of data is well
accepted and could avoid some of the pitfalls of backfilled paper diaries.
PMID- 25847725
TI - Differential improvement of vertical and horizontal metamorphopsia scores after
epiretinal membrane vitrectomy with ILM peeling.
PMID- 25847726
TI - Advances in experimental systems to study hepatitis C virus in vitro and in vivo.
AB - Hepatitis C virus (HCV) represents a global health concern affecting over 185
million people worldwide. Chronic HCV infection causes liver fibrosis and
cirrhosis and is the leading indication for liver transplantation. Recent
advances in the field of direct-acting antiviral drugs (DAAs) promise a cure for
HCV in over 90% of cases that will get access to these expensive treatments.
Nevertheless, the lack of a protective vaccine and likely emergence of drug
resistant viral variants call for further studies of HCV biology. With
chimpanzees being for a long time the only non-human in vivo model of HCV
infection, strong efforts were put into establishing in vitro experimental
systems. The initial models only enabled to study specific aspects of the HCV
life cycle, such as viral replication with the subgenomic replicon and entry
using HCV pseudotyped particles (HCVpp). Subsequent development of protocols to
grow infectious HCV particles in cell-culture (HCVcc) ignited investigations on
the full cycle of HCV infection and the virus-host interactions required for
virus propagation. More recently, small animal models permissive to HCV were
generated that allowed in vivo testing of novel antiviral therapies as well as
vaccine candidates. This review provides an overview of the currently available
in vitro and in vivo experimental systems to study HCV biology. Particular
emphasis is given to how these model systems furthered our understanding of virus
host interactions, viral pathogenesis and immunological responses to HCV
infection, as well as drug and vaccine development.
PMID- 25847727
TI - Surgical treatment options for aggressive osteoblastoma in the mobile spine.
AB - PURPOSE: Osteoblastoma (OBL) is a benign bone tumor with considerable recurrence
potential. Resection is the mainstay for the treatment of Enneking stage 3 (st.
3) OBL. This retrospective study aimed to verify the appropriate surgical
strategy for st. 3 lesions in the mobile spine. METHODS: 19 cases of st. 3 OBL
was diagnosed between 2001 and 2011. Clinical, radiological, surgical, and follow
up data were analyzed. This series included 14 men and 5 women and the mean age
at diagnosis was 30.4 years. The lesions were located in the cervical spine in
ten cases, in the thoracic spine in eight, and in the lumbar spine in one.
Fourteen patients were surgically treated for the first time (intact cases), and
five were referred to us after previous unsuccessful treatments (non-intact
cases). RESULTS: Before 2008, 11 patients underwent curettage followed by
radiotherapy, including 5 non-intact cases and 6 intact cases. Tumor recurrence
was observed in all five non-intact cases and four of the six intact cases. After
2008, eight intact patients underwent intralesional vertebrectomy, including six
who underwent piecemeal total vertebrectomy and two who underwent intralesional
en bloc vertebrectomy. All the eight patients had embolization before surgery. 18
patients had an average 67.3 months (range 36-148 months) of follow-up.
Recurrence was not observed in any of these eight cases with intralesional
vertebrectomy. CONCLUSION: Intralesional total vertebrectomy might be an
appropriate choice for intact st. 3 OBL spine lesions. More cases with longer
follow-up periods should be recruited in the future to better understand the
treatment options available for this disease.
PMID- 25847728
TI - Neck range of motion measurements using a new three-dimensional motion analysis
system: validity and repeatability.
AB - PURPOSE: Neck movement is important for many activities of daily living (ADL).
Neck disorders, such as cervical spondylosis and whiplash can limit neck movement
and ADL. The cervical range of motion (CROM) device has been recently used to
measure neck range of motion (ROM); however, this measurement includes trunk
motion, and therefore does not represent a pure neck ROM measurement. The authors
aimed to develop a new method to establish pure neck ROM measurements during
flexion, extension, lateral bending, and rotation using a three-dimensional
motion analysis system, VICON. METHODS: Twelve healthy participants were
recruited and neck ROMs during flexion, extension, lateral bending, and rotation
were measured using VICON and the CROM device. Test-retest repeatability was
assessed using interclass correlation coefficients (ICCs), standard error of
measurement (SEM), and minimal detectable change (MDC). Validity between two
measurements was evaluated using a determination coefficient and Pearson's
correlation coefficient. RESULTS: ICCs of neck ROM measured using VICON and the
CROM device were all at substantial or almost perfect levels [VICON: ICC(1,2) =
0.786-0.962, the CROM device: ICC(1,2) = 0.736-0.950]. Both SEMs and MDCs were
low in all measurement directions (VICON: SEM = 1.3 degrees -4.5 degrees , MDC =
3.6 degrees -12.5 degrees ; the CROM device: SEM = 2.2 degrees -3.9 degrees , MDC
= 6.1 degrees -10.7 degrees ). Determination coefficients (R(2)s) and Pearson's
correlation coefficients (rs) between the two measurement methods were high (R(2)
= 0.607-0.745, r = 0.779-0.863). CONCLUSIONS: VICON is a useful system to measure
neck ROMs and evaluate the efficacy of interventions, such as surgery or
physiotherapeutic exercise.
PMID- 25847729
TI - The fate of adjacent segments with pre-existing degeneration after lumbar
posterolateral fusion: the influence of degenerative grading.
AB - PURPOSE: To evaluate the impact of pre-existing disc degeneration and its extent
on future adjacent segment degeneration (ASDeg) after lumbar posterolateral
fusion (PLF). METHODS: A total of 102 patients who had undergone PLF for
degenerative lumbar diseases from January 2006 to December 2008 were
retrospectively reviewed by using radiography and clinical evaluation. The
University of California at Los Angeles (UCLA) grading scale was used to evaluate
the extent of disc degeneration. The Visual Analog Scale, Oswestry Disability
Index, and SF-36 questionnaire were used to evaluate clinical outcomes. RESULTS:
The overall prevalence of radiological ASDeg was 25.5 %, and the prevalence of
ASDeg for the cranial and caudal levels was 19.6 and 15.1 %, respectively. The
prevalence of ASDeg in one-, two-, and three-level fusion was 15.8, 26.3, and 50
%, respectively (p = 0.008). For the cranial level, the preoperative UCLA grade
A, B, and C groups had prevalence values for ASDeg of 13.5, 28.6, and 42.9 %,
respectively (p = 0.026). A higher prevalence of ASDeg was found in cranial discs
with pre-existing degeneration than in the group without pre-existing
degeneration (p = 0.012). The group without pre-existing degeneration showed
better outcomes. For the caudal level, there was no significant difference in
ASDeg prevalence. At final follow-up, the group without pre-existing disc
degeneration showed better outcomes than the group with pre-existing disc
degeneration. CONCLUSIONS: Adjacent segment discs with pre-existing degeneration
had a higher likelihood of ASDeg progression compared with normal discs,
especially for those classified as UCLA grade C.
PMID- 25847730
TI - Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver
disease in overweight and obese patients.
AB - BACKGROUND & AIMS: Liver ultrasound (US) is usually used in the clinical setting
for the diagnosis and follow-up of patients with nonalcoholic fatty liver disease
(NAFLD). However, no large study has carefully assessed its performance using a
semiquantitative ultrasonographic scoring system in overweight/obese patients, in
comparison to magnetic resonance spectroscopy ((1) H-MRS) and histology. METHODS:
We recruited 146 patients and performed: a liver US using a 5-parameter scoring
system, a liver (1) H-MRS to quantify liver fat content, and a liver biopsy to
assess histology. All measurements were repeated in a subgroup of patients (n =
62) after 18 months of follow-up. RESULTS: The performance of liver US
(parenchymal echo alone) was rather modest, and significantly worse than (1) H
MRS (AUROC: 0.82 [0.69-0.94] vs. 0.96 [0.90-1.00]; P = 0.04). However, the AUROC
improved when different echographic parameters were taken into account (AUROC:
0.89 [0.83-0.96], P = 0.15 against (1) H-MRS). Optimum sensitivity for liver US
was achieved at a liver fat content >=12.5%, suggesting that below this
threshold, liver US is less sensitive. Liver (1) H-MRS showed a high accuracy for
the diagnosis of NAFLD, and correlated strongly with histological steatosis (r =
0.73, P < 0.0001). None of the imaging tests was adequate enough to predict
changes over time in histology. CONCLUSIONS: Despite its widespread use, liver US
has several important limitations that healthcare providers should recognize,
particularly because of its low sensitivity. Using a combination of echographic
parameters, liver US showed a significant improvement in its diagnostic
performance, but still was of limited value for monitoring treatment over time.
PMID- 25847731
TI - Antioxidant-mediated reversal of oxidative damage in mouse modeling of complex I
inhibition.
AB - Mitochondrial dysfunction is a key component of various aging-related pathologies
of the brain that result in dementia. As such, it provides an important avenue in
development of therapeutic interventions for a host of neurological disorders. A
requirement for functional mitochondrial respiratory chain complex I (CI), to
accomplish the normal physiological processes regulating memory, seems intuitive.
In the present study, a synthetic lipoylcarnitine antioxidant (PMX-500FI; 100
mg/kg/day po) was administered to female ICR mice (3-4-month old) that were
subsequently treated with the mitochondrial CI inhibitor, rotenone (400
mg/kg/day). After 1 week, rotenone-induced impairment of neuronal function was
evaluated in the hippocampus, a brain region that is involved in regulating
memory formation. Electrophysiological recordings in live brain slices showed
that long-term potentiation (LTP) was reduced by rotenone exposure (P < 0.05)
while pretreatment with PMX-500FI maintained LTP similar to control levels (P >
0.05). Potentiation during theta burst stimulation (TBS) was similar among
treatment groups (P > 0.05); however, neurotransmitter release, which increased
in control mice after TBS, was lower in rotenone treated mice (P < 0.05), and was
accompanied by reduced basal synaptic transmission (P < 0.05), increased
proapoptotic signaling and decreased extracellular signal-regulated kinase1/2
(ERK1/2) phosphorylation (P < 0.05). For each of these determinations,
pretreatment with PMX-500FI alleviated the harmful effects of rotenone. These
results illustrate that treatment with antioxidant PMX-500FI is protective
against rotenone-induced impairment of neuronal bioenergetics in the mouse
hippocampus, in regard to both excitatory synaptic physiology and proapoptotic
signaling. The protective effect of PMX-500FI against rotenone-induced disruption
of cellular bioenergetics may have important therapeutic implications for
treating aging-related dementia and other diseases related to mitochondrial
dysfunction and/or oxidative damage.
PMID- 25847732
TI - Fruit and vegetable consumption and food values: National patterns in the United
States by Supplemental Nutrition Assistance Program eligibility and cooking
frequency.
AB - BACKGROUND: More frequent cooking at home may help improve diet quality and be
associated with food values, particularly for individuals participating in the
Supplemental Nutrition Assistance Program (SNAP). OBJECTIVE: To examine patterns
of fruit and vegetable consumption and food values among adults (aged 20 and
older) in the United States, by SNAP participation and household cooking
frequency. METHODS: Analysis of cross-sectional 24-hour dietary recall data
obtained from the National Health and Nutrition Examination Survey 2007-2010
(N=9560). RESULTS: A lower percentage of SNAP participants consumed fruit (total:
35% vs. 46%, p=0.001; fresh: 30% vs. 41%, p<0.001) and vegetables (total: 49% vs.
58%, p=0.004; fresh: 35% vs. 47%, p<0.001) than those ineligible for SNAP. Among
SNAP participants, cooking >6times/week was associated with greater vegetable
consumption compared to cooking <2times/week (175g vs. 98g, p=0.003). SNAP
eligible individuals who cooked >=2times/week were more to report price (medium
cookers: 47% vs. 33%, p=0.001; high cookers: 52% vs. 40%, p<0.001), ease of
preparation (medium cookers: 36% vs. 28%, p=0.002; high cookers: 36% vs. 24%,
p<0.001) and how long food keeps (medium cookers: 57% vs. 45%, p<0.001; high
cookers: 61% vs. 50%, p<0.001) as important compared to SNAP-ineligible
individuals. CONCLUSIONS: Fruit and vegetable consumption in the United States is
low regardless of cooking frequency. Efforts to improve diet quality should
consider values on which food purchases are based.
PMID- 25847733
TI - Rapid in vivo multicomponent T2 mapping of human knee menisci.
AB - PURPOSE: To compare multicomponent T2 parameters of menisci measured using
Multicomponent Driven Equilibrium Single Pulse Observation of T1 and T2
(mcDESPOT) in asymptomatic volunteers and osteoarthritis (OA) patients with
intact and torn menisci. MATERIALS AND METHODS: The prospective study was
performed with Institutional Review Board approval and with all subjects signing
written informed consent. mcDESPOT was performed on the knee joint of 12
asymptomatic volunteers and 14 patients with knee OA. Single-component T2
relaxation time (T2Single ), T2 relaxation time of the fast relaxing water
component (T2F ), and the slow relaxing water component (T2S ), and fraction of
the fast relaxing water component (FF ) of the medial and lateral menisci were
measured. Multivariate linear regression models were used to compare mcDESPOT
parameters between normal menisci in asymptomatic volunteers, intact menisci in
OA patients, and torn menisci in OA patients with adjustment for differences in
age between subjects. RESULTS: The mean mcDESPOT parameters for normal menisci in
asymptomatic volunteers, intact menisci in OA patients, and torn menisci in OA
patients were respectively 16.1 msec, 18.8 msec, and 22.7 msec for T2Single ; 9.0
msec, 10.0 msec, and 11.1 msec for T2F ; 24.4 msec, 27.7 msec, and 31.4 msec for
T2S ; and 34%, 32%, 27% for FF . There were significant differences (P < 0.05) in
T2Single , T2F , T2S , and FF between the three groups of menisci. CONCLUSION:
The menisci of OA patients had significantly higher T2Single , T2F , and T2S and
significantly lower FF than normal menisci in asymptomatic volunteers with
greater changes in multicomponent T2 parameters noted in torn than intact menisci
in OA patients.
PMID- 25847734
TI - Improving multivariable prostate cancer risk assessment using the Prostate Health
Index.
AB - OBJECTIVES: To analyse the clinical utility of a prediction model incorporating
both clinical information and a novel biomarker, p2PSA, in order to inform the
decision for prostate biopsy in an Irish cohort of men referred for prostate
cancer assessment. PATIENTS AND METHODS: Serum isolated from 250 men from three
tertiary referral centres with pre-biopsy blood draws was analysed for total
prostate-specific antigen (PSA), free PSA (fPSA) and p2PSA. From this, the
Prostate Health Index (PHI) score was calculated (PHI = (p2PSA/fPSA)*?tPSA). The
men's clinical information was used to derive their risk according to the
Prostate Cancer Prevention Trial (PCPT) risk model. Two clinical prediction
models were created via multivariable regression consisting of age, family
history, abnormality on digital rectal examination, previous negative biopsy and
either PSA or PHI score, respectively. Calibration plots, receiver-operating
characteristic (ROC) curves and decision curves were generated to assess the
performance of the three models. RESULTS: The PSA model and PHI model were both
well calibrated in this cohort, with the PHI model showing the best correlation
between predicted probabilities and actual outcome. The areas under the ROC curve
for the PHI model, PSA model and PCPT model were 0.77, 0.71 and 0.69,
respectively, for the prediction of prostate cancer (PCa) and 0.79, 0.72 and
0.72, respectively, for the prediction of high grade PCa. Decision-curve analysis
showed a superior net benefit of the PHI model over both the PSA model and the
PCPT risk model in the diagnosis of PCa and high grade PCa over the entire range
of risk probabilities. CONCLUSION: A logical and standardized approach to the use
of clinical risk factors can allow more accurate risk stratification of men under
investigation for PCa. The measurement of p2PSA and the integration of this
biomarker into a clinical prediction model can further increase the accuracy of
risk stratification, helping to better inform the decision for prostate biopsy in
a referral population.
PMID- 25847735
TI - [Is there a place for thrombin generation assay in routine clinical laboratory?].
AB - Laboratory diagnosis of coagulopathies primarily relies on assays selectively
exploring either the extrinsic (PT), the intrinsic (aPTT) or the common (TT)
pathway of the coagulation system. Although these tests are very useful to
rapidly identify severe coagulation disorders or to monitor anticoagulant
therapy, they only poorly correlate with the clinical manifestations. Global
assays that evaluate the whole coagulation process could potentially more
accurately reflect the hemorrhagic or thrombotic phenotype of an individual.
Thrombin generation assay (TGA), first described in the 1950's, has been
developed and automated in the 1990's. This technique is widely used in
fundamental research but has yet failed to integrate clinical laboratories. In
this article, we describe TGA and review its clinical applications. Laboratory
aspects and technical issues will also be discussed.
PMID- 25847736
TI - [Urinary biomarkers of kidney dysfunction].
AB - The early diagnosis of chronic kidney disease (CKD) is based on the detection of
markers of renal damage in urine collection. These urinary bio-markers are
measurable before the appearance of functional defect, which is diagnosed with a
decrease of glomerular filtration rate. Albuminuria, preferentially expressed as
urinary albumin/creatinin ratio, is one of the marker of CKD. But today, other
urinary biomarkers, monitoring tubulointersticial damage, are of interest in
early diagnosis of CKD. In acute kidney injury, these markers could improve
diagnostic tests, since they increase faster than serum creatinin. We propose a
review of the urinary biomarkers of renal dysfunction used in routine clinical
practice in 2015.
PMID- 25847737
TI - [Accumulation of p53 protein and overexpression of the HER3 receptor in
colorectal cancer].
AB - In patients with colorectal cancer, nuclear accumulation of p53 is often
associated with poor prognosis and resistance to chemotherapy. Overexpression of
HER3 is associated with poor prognosis and resistance to therapy targeting EGFR.
Our study was performed on 16 samples of colorectal adenocarcinomas. The pieces
fixed in formalin were embedded in paraffin. The study of the expression of p53
and HER3 is performed by immunohistochemical technique. Immunohistochemical study
of the expression of p53 showed nuclear accumulation of this protein in 87% of
colorectal adenocarcinomas analyzed. Regarding the HER3 receptor overexpression
was observed in 56% of cases. Overall, 50% of the cases co-expressed p53 and
HER3. HER3 and p53 are important markers of colorectal cancer because they
provide information about the distinctive biological characteristics of tumors.
The prognostic and predictive value of the combination of these two markers could
be an important clinical tool.
PMID- 25847738
TI - [External quality assessment in clinical biochemistry laboratories: pilot study
in 11 laboratories of Lome (Togo)].
AB - This study aims to evaluate the performance of a few biochemistry analysis and
make recommendations to the place of the stakeholders. It is a cross-sectional
study conducted between the October 1(st), 2012 and the July 31, 2013 bearing on
the results of 5 common examinations of clinical biochemistry, provided by 11
laboratories volunteers opening in the public and private sectors. These
laboratories have analysed during the 3 cycles, 2 levels (medium and high) of
serum concentration of urea, glucose, creatinine and serum aminotransferases. The
performance of laboratories have been determined from the acceptable limits
corresponding to the limits of total errors, defined by the French Society of
Clinical Biology (SFBC). A system of internal quality control is implemented by
all laboratories and 45% of them participated in international programs of
external quality assessment (EQA). The rate of acceptable results for the entire
study was of 69%. There was a significant difference (p<0.002) between the
performance of the group of laboratories engaged in a quality approach and the
group with default implementation of the quality approach. Also a significant
difference was observed between the laboratories of the central level and those
of the peripheral level of our health system (p<0.047). The performance of the
results provided by the laboratories remains relatively unsatisfactory. It is
important that the Ministry of Health put in place a national program of EQA with
mandatory participation.
PMID- 25847740
TI - Autosomal dominant polycystic kidney disease: identification of two
polymorphisms.
AB - The identification of polymorphism A4059V associated with the 12276 A>G at exon
45 of the PKD1 gene in a Tunisian polycystic patient.
PMID- 25847739
TI - [Antimicrobial activity of Actinomycetale isolated from the lagoon in Algeria].
AB - In the aim of the study of the taxonomy and the antimicrobial activity, a strain
of actinomycete SM2/2GF which was isolated from sediment of the lagoon El-Mellah
which is situated in the city of El-Kala in the Northeast of Algeria, was tested
against diverse pathogenic microorganisms and against a Gram-negative bacterium
Pseudomonas alcaliphila which was isolated from water of the lagoon El-Mellah.
The phenotypic and the molecular characteristics show that the isolate SM2/2GF
belongs to the kind Streptomyces. This strain showed an antimicrobial activity
against a Gram-negative bacterium Pseudomonas alcaliphila and the positive-Gram
bacteria as Staphylococcus aureus, methicillin-resistant Staphylococcus aureus
(MRSA), Bacillus subtilis, Enterococcus faecalis, as well as the yeast Candida
albicans. It has no activity against Pseudomonas aeruginosa. The interesting
antimicrobial activity of the strain SM2/2GF against the pathogenic
microorganisms could encourage further researches on one or several bioactive
molecules which it secretes.
PMID- 25847741
TI - [An acute monoclonal gammopathy?].
AB - Serum protein electrophoresis is commonly used in case of acute or chronic renal
failure. It can lead to the etiologic diagnosis by detecting monoclonal
gammopathies which are frequently complicated by renal failure, such as cast
nephropathy, Randall's disease or amyloidosis, or to explore an associated
inflammatory syndrome. We report the occurrence of two monoclonal components in a
patient without any monoclonal component 10 days earlier. The sudden appearance
of these two monoclonal components associated to the context of sepsis of urinary
origin suggested the diagnosis of transient monoclonal gammopathy. This
hypothesis was confirmed by monitoring serum protein electrophoresis that showed
a gradual decrease of these two monoclonal components few weeks after the
resolution of the infectious disease. The main etiological factors of transient
monoclonal gammopathies are infectious or autoimmune diseases. In this context,
it is important to delay the achievement of serum protein electrophoresis after
the acute episode, in order to avoid to falsely conclude to hematologic
malignancy diagnosis. This can prevent costly biological examinations of these
transient monoclonal gammopathies and invasive procedures like bone marrow
examination.
PMID- 25847743
TI - [Prolonged molecular response induced by imatinib in Philadelphia positive acute
lymphoblastic leukemia A case report and brief review].
AB - Philadelphia or BCR-ABL positive acute lymphoblastic leukemia (PH+ ALL) is the
most common and severe of adult ALL. The only potentially curator treatment
remains allogeneic hematopoietic stem cells transplantation (SCT) in first
complete remission. The use of imatinib has revolutionized the treatment of
chronic myeloid leukemia. Its incorporation into PH + ALL protocols also improved
the prognosis of this disease giving better complete remission rates compared to
chemotherapy alone. The treatment of patients not eligible for SCT remains
controversial. Prolonged use of high dose tyrosine kinase inhibitors (TKI) (ie:
imatinib at 600 or 800 mg/j) as maintenance therapy seems to be a reasonable
approach. We present a case of prolonged molecular remission of PH+ ALL under TKI
alone as maintenance therapy.
PMID- 25847742
TI - [A case of bisalbuminemia in a patient with digestive adenocarcinoma].
AB - Bisalbuminemia whether hereditary or acquired, is a rare electrophoretic
abnormality of albumin, characterized by a duplication of the albumin fraction on
the electrophoretic trace of the serum proteins. This duplication reflects the
presence in the same individual normal plasma albumin and a modified albumin.
OBSERVATION: This is a patient of 62 years hospitalized at the Internal Medicine
Department of HMIMV for liver metastases of gastrointestinal adenocarcinoma and
including serum protein electrophoresis (EP) performed on capillary (Capillarys
society Sebia) reveals bisalbuminemia. The family investigation has ruled that
inheritance of acquired bisalbuminemia to retain appearance. COMMENT:
Bisalbuminemia acquired outside treatment with high doses of beta-lactam
antibiotics, chronic pancreatitis with pseudocyst rupture or fixing a monoclonal
immunoglobulin on albumin in the myeloma subjects is an exceptional event. The
pathophysiologic mechanism in the reported cases remains unexplained as is also
the case of acquired bisalbuminemias associated with other pathological contexts
(Alzheimer's disease nephrotic syndrome). CONCLUSION: To the best of our
knowledge, the bisalbuminemia in the gastrointestinal adenocarcinoma liver
metastases has not been reported to date, hence the importance of the reported
cases.
PMID- 25847744
TI - [Free thyroxine immunoassay: analytical review].
AB - Thyroid hormones assays (T4 and T3) are limited to the free forms with hormonal
activity, the only ones useful for the assessment of thyroid function. Free
thyroxine assays are part of prescribed parameters by the physician once known
plasma TSH concentration. A reference method exists, but immunoassays are the
most commonly technics used in current practice. After a reminder of the
iodothyronine biochemistry and physiology, the authors discuss preanalytical and
analytical steps in detail, focusing on the possible pitfalls.
PMID- 25847745
TI - [Immunoanalytical profile of free tri-iodothyronine].
AB - Tri-iodothyronine (T3) is the active form of thyroid hormone at the nuclear cell
level. About 80% of tri-iodothyronine is produced by peripheral deiodination of
thyroxine. The determination of the free form of this hormone is useful for the
diagnosis and the follow-up of hyperthyroidism. In routine clinical laboratories,
immunoassays remain the most used technics. After recalling the main points
related to the physiological data, the authors point out the possible errors
during the analytical steps of the assay.
PMID- 25847746
TI - [TSH-receptor antibodies: immunoanalytical characteristics].
AB - Besides the main biochemical characteristics of anti TSH-receptor antibodies,
this paper points out the optimal conditions for their assays and the
interpretation of results.
PMID- 25847747
TI - [Guidelines for certification of Activated clotting time (ACT) according to the
EN ISO 22870 standards].
AB - Point of care testing (POCT) must comply with regulatory requirements according
to standard EN ISO 22870, which identify biologists as responsible for POCT.
Activated clotting time (ACT) is mandatory to monitor on whole blood,
anticoagulation achieved by unfractionated heparin during cardiopulmonary bypass
(CPB) or cardiac catheterization. This test has no equivalent in the laboratory.
With the aim to help the multidisciplinary groups for POCT supervision when they
have to analyse the wish of medical departments to use ACT and to help the
biologists to be in accordance with the standard, we present the guidelines of
the GEHT (Groupe d'etude d'hemostase et thrombose) subcommittee "CEC et Biologie
delocalisee" for the certification of ACT. These guidelines are based on the SFBC
guidelines for the certification of POCT and on the analysis of the literature to
ascertain the justification of clinical need and assess the analytical
performance of main analyzers used in France, as well as on a survey conducted
with French and Belgian biologists.
PMID- 25847748
TI - [Measurements of PSA and of vitamin D: a period of 3-months of use of special
forms based on the guidelines of the Haute autorite de sante shows a clear
improvement of prescription behaviors].
AB - In France practice guidelines of the Haute Autorite de sante (HAS) are not
implemented as often as they should. As a consequence resources are wasted that
could be useful elsewhere. In Avril 2014 prescription-forms were introduced in
our hospital for PSA and for vitamin-D. If those forms were not filled-in by the
physicians, then PSA and vitamin-D were not measured any more by our laboratory.
PSA was measured in only two circumstances: therapeutic follow-up of, or
screening for, prostate cancer. Patients had to give their formal consent for
being screened with PSA. Vitamin-D was measured in the only six circumstances
recommended by the HAS. After a few months of use of these two forms we observe a
sharp decrease in PSA, and even more so in vitamin D, measurements. Our
prescription-forms' legitimacy is high because they are based on governmental
guidelines. All the more since the values that are promoted in these guidelines
clearly cover the four core principles of bioethics, that is beneficence, non
malevolence, respect for the patient's autonomy (particularly for PSA) and
equity. Our results need to be confirmed over a longer period of time, and to be
analysed in more detail, particularly regarding the way consent forms are filled
in by the patients.
PMID- 25847749
TI - Simple Resolution of Enantiomeric NMR Signals of alpha-Amino Acids by Using
Samarium(III) Nitrate With L-Tartarate.
AB - Readily available L-tartaric acid, which is a bidentate ligand with two chiral
centers forming a seven-membered chelate ring, was applied to the chiral ligand
for the chiral nuclear magnetic resonance (NMR) shift reagent of samarium(III)
formed in situ. This simple method does not cause serious signal broadening in
the high magnetic field. Enantiomeric (13)C and (1)H NMR signals and enantiotopic
(1)H NMR signals of alpha-amino acids were successfully resolved at pH 8.0 and
the 1:3 molar ratio of Sm(NO3)3:L-tartaric acid. It is elucidated that the
enantiomeric signal resolution is attributed to the anisotropic magnetic
environment for the enantiomers induced by the chiral L-tartarato samarium(III)
complex rather than differences in stability of the diastereomeric substrate
adducts. The present (13)C NMR signal resolution was also effective for the
practical simultaneous analysis of plural kinds of DL-amino acids.
PMID- 25847750
TI - Brain derived neurotrophic factor (BDNF) and autism spectrum disorders (ASD) in
childhood.
AB - BACKGROUND: Neurotrophic factors are essential regulators of neuronal maturation
including synaptic synthesis. Among those, Brain derived neurotrophic factor
(BDNF) has been in particular focus in the understanding of autism spectrum
disorders (ASD). PURPOSE: The aim of our study was to investigate whether BNDF
could be used as diagnostic/biological marker for ASD. For this purpose we
examined the plasma levels of BDNF and the precursors pro- BDNF in patients with
ASD and compared it with non-autistic controls; determined whether there was a
correlation between the BDNF and proBDNF levels and clinical severity. We also
investigated the coding region of BDNF identify for well-variations which could
be associated to ASD. METHODS: The 65 ASD patients (51 boys) were enrolled from a
recent completed epidemiological survey covering two counties (Oppland and
Hedmark) in Norway. The mean age of the total number of children who participated
in this study was 11,7 years. 30 non-autistic children were included as controls,
14 boys and 16 girls. The mean age was 11.3 years. Exclusion criteria for control
group were individuals suffering from either neurological, endocrine, or immune
insuffiency. RESULTS AND CONCLUSIONS: Patients with ASD were characterized by
moderately but significantly elevated plasma levels of BDNF compared to matched
controls. No differences were observed in the proBDNF level between patients and
controls. Within the ASD group, children with intellectual disability
demonstrated increased BDNF, but not proBDNF levels, while the presence of ADHD
had no impact on circulating proBDNF or BDNF. No further associations between
plasma proBDNF or BDNF and other clinical demographics were observed.
PMID- 25847751
TI - ABCB1 gene variants and antidepressant treatment outcome: A meta-analysis.
AB - The efflux pump P-glycoprotein (P-gp), a gene product of the ABCB1 gene, plays a
pivotal role in the transfer of various molecules across the blood-brain barrier.
P-gp protects the brain by selectively extruding its substrates, including
certain antidepressive drugs, thereby limiting their uptake into the brain. Uhr
et al. [2008] first showed that ABCB1 variants predicted the remission to
antidepressants with P-gp substrate properties in patients suffering from major
depression (MD). Other studies investigating the influence of ABCB1 polymorphisms
on antidepressant treatment response produced inconclusive results. In this meta
analysis, we systematically summarized 16 pharmacogenetic studies focused on the
association of ABCB1 variants and antidepressant treatment outcome in patients
with MD (overall n = 2695). We investigated the association of treatment outcome
and six ABCB1 single nucleotide polymorphisms (SNPs): rs2032583, rs2235015,
rs2235040, rs1045642, rs2032582, rs1128503. We stratified for admission status,
ethnicity, and prescription of concomitant medication. SNP rs2032583 showed a
nominally significant association across all studies (P = 0.035, SNP was studied
in a total of 2,037 patients) and a significant Bonferroni-corrected association
among inpatients (P = 1.5 * 10(-05) , n = 485). Also SNP rs2235015 was
significantly associated with antidepressant treatment outcome withstanding
Bonferroni correction (P = 3.0 * 10(-04) ) among inpatients in a smaller
subsample (n = 195). There were no significant associations of the other SNPs
tested with antidepressant treatment outcome. Future pharmacogenetic association
studies should focus on the role of the ABCB1 SNP rs2032583 in antidepressant
outcome prediction.
PMID- 25847752
TI - Enhancing agents for phytoremediation of soil contaminated by cyanophos.
AB - Cyanophos is commonly used in Egypt to control various agricultural and
horticultural pests. It is a strong contaminant in the crop culturing
environments because it is highly persistent and accumulates in the soil. This
contaminant can be removed by phytoremediation, which is the use of plants to
clean-up pollutants. Here we tested several several strategies to improve the
effectiveness of this technology, which involved various techniques to solubilize
contaminants. The phytoremediation efficiency of Plantago major L. was improved
more by liquid silicon dioxide (SiO2) than by other solubility-enhancing agents,
resulting in the removal of significant amounts of cyanophos from contaminated
soil. Liquid SiO2 increased the capacity of P. major L. to remove cyanophos from
soil by 45.9% to 74.05%. In P. major L. with liquid SiO2, leaves extracted more
cyanophos (32.99 ug/g) than roots (13.33 ug/g) over 3 days. The use of
solubilization agents such as surfactants, hydroxypropyl-beta-cyclodextrin
(HPbetaCD), natural humic acid acid (HA), and Tween 80 resulted in the removal of
60 convergents of cyanophos from polluted soil. Although a batch equilibrium
technique showed that use of HPbetaCD resulted in the efficient removal of
cyanophos from soil, a greater amount of cyanophos was removed by P. major L.
with SiO2. Moreover, a large amount of cyanophos was removed from soil by rice
bran. This study indicates that SiO2 can improve the efficiency of
phytoremediation of cyanophos.
PMID- 25847753
TI - Occurrences of pharmaceuticals in drinking water sources of major river
watersheds, China.
AB - Pharmaceuticals in drinking water sources (DWSs) have raised significant concerns
for their persistent input and potential human health risks. Currently, little is
known about the occurrence of pharmaceuticals in DWSs in China. In this study, a
survey for multi-class pharmaceuticals in DWSs of five major river watersheds in
China was conducted from 2012 to 2013. Samples were collected from 25 sampling
sites in rivers and reservoirs. 135 pharmaceuticals were analyzed using solid
phase extraction and ultra-performance liquid chromatography tandem mass
spectrometry. The results showed that a total of 70 pharmaceuticals were present
in the samples, and the most frequently detected ones included sulfonamides,
macrolides, antiepileptic drugs, anti-inflammatory drugs, and beta-blockers, etc.
Amongst these, maximum concentrations of lincomycin, sulfamethoxazole,
acetaminophen and paraxanthine were between 44 ng/L and 134 ng/L, and those of
metoprolol, diphenhydramine, venlafaxine, nalidixic acid and androstenedione were
less than 1 ng/L. Concentrations of the two that were most persistent, DEET and
carbamazepine, were 0.8-10.2 ng/L and 0.01-3.5 ng/L, respectively. Higher
concentrations of cotinine were observed in warm season than in cold season,
while concentrations of lincomycin were the opposite. In a causality analysis,
the occurrence of pharmaceuticals in DWSs depends mainly on the detection limits
of the methods, their usage and the persistence in the aquatic environment.
PMID- 25847754
TI - Brief Report: Vision in Children with Autism Spectrum Disorder: What Should
Clinicians Expect?
AB - Anomalous visual processing has been described in individuals with autism
spectrum disorder (ASD) but relatively few studies have profiled visual acuity
(VA) in this population. The present study describes presenting VA in children
with ASD (n = 113) compared to typically developing controls (n = 206) and best
corrected visual acuity (BCVA) in a sub-group of children with ASD (n = 29).
There was no statistically significant difference in presenting VA between groups
(z = -1.75, p = 0.08); ASD group median VA (interquartile range, IQR) -0.05
logMAR (IQR: -0.125 to 0.025 logMAR) and typically developing control group
0.075 logMAR (IQR: -0.150 to -0.025 logMAR). Median BCVA was -0.175 logMAR (IQR:
0.200 to -0.125 logMAR) for the ASD sub-group. Clinicians should not anticipate
reduced VA when assessing children with ASD.
PMID- 25847755
TI - Examination of the Korean Modified Checklist of Autism in Toddlers: Item Response
Theory.
AB - The study examined the clinical utility and psychometric properties of the Korean
Modified Checklist of Autism in Toddlers (K-M-CHAT)-2. A sample of 2300 parents
of 16- to 36-month-old children was recruited across South Korea. A phone
interview was utilized to follow up with participants who initially screened
positive for autism spectrum disorder (ASD). Item response theory was applied to
assess the psychometric properties of the K-M-CHAT-2. Parents' responses were
substantially changed after the follow-up, and the final screen-positive rate was
2.3 %. Results indicated that the psychometric properties of items 1, 3, 11, 18
and 22 were not as strong as the other items. The K-M-CHAT-2 is a useful ASD
screening test when implemented with a follow-up.
PMID- 25847756
TI - Psychosocial Adjustment and Sibling Relationships in Siblings of Children with
Autism Spectrum Disorder: Risk and Protective Factors.
AB - This study compared sibling adjustment and relationships in siblings of children
with Autism Spectrum Disorder (ASD-Sibs; n = 69) and siblings of children with
typical development (TD-Sibs; n = 93). ASD-Sibs and TD-Sibs demonstrated similar
emotional/behavioral adjustment. Older male ASD-Sibs were at increased risk for
difficulties. Sibling relationships of ASD-Sibs involved less aggression, less
involvement, and more avoidance than those of TD-Sibs. Partial support for a
diathesis-stress conceptualization of sibling difficulties was found for ASD
Sibs. For TD-Sibs, broader autism phenotype (BAP) was related to psychosocial
difficulties regardless of family stressors. For ASD-Sibs, BAP was related to
difficulties only when family stressors were present. This suggests that having a
sibling with ASD may be a protective factor that attenuates the negative impact
of sibling BAP.
PMID- 25847758
TI - Catalytic asymmetric hydrogenation of quinoline carbocycles: unusual
chemoselectivity in the hydrogenation of quinolines.
AB - The reduction of quinolines selectively took place on their carbocyclic rings to
give 5,6,7,8-tetrahydroquinolines, when the hydrogenation was conducted in the
presence of a Ru(eta(3)-methallyl)2(cod)-PhTRAP catalyst. The chiral ruthenium
catalyst converted 8-substituted quinolines into chiral 5,6,7,8
tetrahydroquinolines with up to 91 : 9 er.
PMID- 25847757
TI - Are Autistic Traits in the General Population Related to Global and Regional
Brain Differences?
AB - There is accumulating evidence that autistic-related traits in the general
population lie on a continuum, with autism spectrum disorders representing the
extreme end of this distribution. Here, we tested the hypothesis of a possible
relationship between autistic traits and brain morphometry in the general
population. Participants completed the short autism-spectrum quotient
questionnaire (AQ); T1-anatomical and DWI-scans were acquired. Associations
between autistic traits and gray matter, and white matter microstructural
integrity were performed on the exploration-group (N = 204; 105 males, M-age =
22.85), and validated in the validation-group (N = 304; 155 males, M-age =
22.82). No significant associations were found between AQ-scores and brain
morphometry in the exploration-group, or after pooling the data. This questions
the assumption that autistic traits and their morphological associations do lie
on a continuum in the general population.
PMID- 25847759
TI - Experiences with the flow-through radial forearm flap as a bridge in lower
extremity reconstruction.
AB - Various techniques have been proposed in order to overcome recipient vessel
problems in microsurgery. In cases with no suitable recipient vessels close to
the defect, the flow-through flap is a valuable and reliable alternative for
accessing healthy recipient vessels in a single stage. We describe our
experiences with combined flaps and discuss the advantages of the flow-through
radial forearm flap as a bridge. Between 2003 and 2009, eight combined flaps were
used to reconstruct soft-tissue defects of lower extremities. Seven patients had
acute or subacute wound with exposed bone and vascular injury caused by trauma,
one had a chronic nonhealing wound. The flow-through radial forearm flap was used
as a bridge flap with combined a cover flap in all cases. Radial forearm flaps
provided recipient vessel lengthening. In one patient, the distal ALT flap failed
and replaced with latissimus dorsi flap. Other postoperative courses were
uneventful and all of flaps survived. In one patient although the flaps were
healthy, sepsis developed and the extremity was amputated. Recovery and
ambulation were achieved in the remaining patients. Combined flaps with the flow
through radial forearm flap are an appropriate technique for overcoming recipient
vessel problems. Although the technique involves a more complicated procedure and
increases the number of microvascular anastomoses, it is a valuable, safe and
comfortable alternative in selected cases.
PMID- 25847760
TI - Comparison of properties of new sources of partially purified inulin to those of
commercially pure chicory inulin.
AB - Newly developed inulin powders were prepared from roots of Asparagus falcatus
(AF) and Taraxacum javanicum (TJ) plants grown in Sri Lanka. Inulin content,
analyzed by enzymatic spectrophotometric as well as high-performance liquid
chromatographic methods, showed that AF and TJ inulin powders contain 65.5% and
45.4% (dry wt) inulin, respectively, compared with 72% dry wt in the commercially
available chicory inulin. Treating the AF and TJ inulin powders using ion
exchange techniques significantly (P < 0.05) reduced their contents of micro (Zn,
Cu, Mn, Fe) and macro (Na, K, Ca, Mg) elements. Enzymatic hydrolysis of inulin
into fructose and glucose by fructanase, and FT-IR analyses proved that the
developed AF and TJ inulins have characteristic molecular composition similar to
commercial inulin. TJ inulin contained significantly (P < 0.05) greater amounts
of total phenolics (4.37 mg GAE/g), total flavonoids (2.79 mg QE/g), and
antioxidant capacity (833.11 mM TE/g) than AF inulin, which contained 1.33 mg
GAE/g of total phenolics, 0.43 mg QE/g of total flavonoids, and 406.26 mM TE/g
antioxidant capacity. The current study suggests that the newly developed inulin
from AF and TJ roots could be used as an alternative commercial source of inulin
for the food industry.
PMID- 25847764
TI - Acupuncture practice acts: a profession's growing pains.
AB - State legislation that authorizes any healthcare profession is known as the
Practice Act. In order for a profession to establish a recognizable national
presence and be integrated into mainstream medicine, all the state Practice Acts
must evidence consistency. The extent to which state Practice Acts fail to
exhibit consistency can inhibit the ability of the profession to grow and become
successful. We looked at the histories of other health professions, along with
the 45 acupuncture Practice Acts in the USA, in order to understand the time worn
paths that lead to integration in the mainstream and how the acupuncture
profession might benefit.
PMID- 25847765
TI - Design, synthesis, biological evaluation and molecular docking studies of
phenylpropanoid derivatives as potent anti-hepatitis B virus agents.
AB - A series of phenylpropanoid derivatives were synthesized, and their anti
hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the
synthesized derivatives showed effective anti-HBV activity. Of these compounds,
compound 4c-1 showed the most potent anti-HBV activity, demonstrating potent
inhibitory effect not only on the secretion of HBsAg (IC50 = 14.18 MUM, SI =
17.85) and HBeAg (IC50 = 6.20 MUM, SI = 40.82) secretion but also HBV DNA
replication (IC50 = 23.43 MUM, SI = 10.80). The structure-activity relationships
(SARs) of phenylpropanoid derivatives had been discussed, which were useful for
phenylpropanoid derivatives to be explored and developed as novel anti-HBV
agents. Moreover, the docking study of all synthesized compounds inside the HLA-A
protein (PDB ID: 3OX8) active site were carried out to explore the molecular
interactions and a molecular target for activity of phenylpropanoid derivatives
with the protein using a moe-docking technique. This study identified a new class
of potent anti-HBV agents.
PMID- 25847766
TI - A new delivery system for auristatin in STxB-drug conjugate therapy.
AB - A key challenge in anticancer therapy is to gain control over the biodistribution
of cytotoxic drugs. The most promising strategy consists in conjugating drugs to
tumor-targeting carriers, thereby combining high cytotoxic activity and specific
delivery. To target Gb3-positive cancer cells, we exploit the non-toxic B-subunit
of Shiga toxin (STxB). Here, we have conjugated STxB to highly potent auristatin
derivatives (MMA). A former linker was optimized to ensure proper drug-release
upon reaching reducing environments in target cells, followed by a self
immolation step. Two conjugates were successfully obtained, and in vitro assays
demonstrated the potential of this targeting system for the selective elimination
of Gb3-positive tumors.
PMID- 25847767
TI - Synthesis and anticancer activity of N-substituted 2-arylquinazolinones bearing
trans-stilbene scaffold.
AB - A novel series of 2-arylquinazolinones 7a-o bearing trans-stilbene moiety were
designed, synthesized, and evaluated against human breast cancer cell lines
including human breast adenocarcinoma (MCF-7 and MDA-MB-231) and human ductal
breast epithelial tumor (T-47D). Among the tested compounds, the sec-butyl
derivative 7h showed the best profile of activity (IC50 < 5 MUM) against all cell
lines, being 2-fold more potent than standard drug, etoposide. Our investigation
revealed that the cytotoxic activity was significantly affected by N3-alkyl
substituents. Furthermore, the morphological analysis by acridine orange/ethidium
bromide double staining test and flow cytometry analysis indicated that the
prototype compound 7h can induce apoptosis in MCF-7 and MDA-MB-231 cells.
PMID- 25847768
TI - Development of benzimidazole derivatives to inhibit HIV-1 replication through
protecting APOBEC3G protein.
AB - Human APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like
3G, A3G) is a potent restriction factor against human immunodeficiency virus type
1 (HIV-1) by inducing hypermutation of G to A in viral genome after its
incorporation into virions. HIV-1 Vif (Virion Infectivity Factor) counteracts A3G
by inducing ubiquitination and proteasomal degradation of A3G protein. Vif-A3G
axis therefore is a promising therapeutic target of HIV-1. Here we report the
screening, synthesis and SAR studies of benzimidazole derivatives as potent
inhibitors against HIV-1 replication via protecting A3G protein. Based on the
steep SAR of the benzimidazole scaffold, we identified compound 14 and 26 which
provided the best potency, with IC50 values of 3.45 nM and 58.03 nM respectively
in the anti-HIV-1 replication assay in H9 cells. Compound 14 and 26 also afforded
protective effects on A3G protein level. Both compounds have been proved to be
safe in acute toxicological studies. Taken together, we suggest that these two
benzimidazole derivatives can be further developed as a new category of anti-HIV
1 leads.
PMID- 25847769
TI - Novel imidazo[2,1-b]-1,3,4-thiadiazoles as promising antifungal agents against
clinical isolate of Cryptococcus neoformans.
AB - We herein report the synthesis and in vitro antimicrobial evaluation of twenty
five novel hybrid derivatives of imidazo [2,1-b]-1,3,4-thiadiazole containing
chalcones (5a-o) and Schiff bases (6a-j) against three fungal strains (Candida
albicans, Cryptococcus neoformans and Aspergillus niger). Most of the tested
compounds displayed substantial anti-fungal activity with MICs ranging between
1.56 and 100 MUg/mL. Compounds 5a, 5b and 5n exhibited promising activity against
C. neoformans at a MIC 1.56 MUg/mL. In addition, compound 5n also demonstrated
significant antifungal activity against the clinical isolates of C. neoformans at
MIC 3.125 MUg/mL. However, moderate activity was observed for these compounds
against four bacterial strains (Staphylococcus aureus, Bacillus subtilis,
Escherichia coli and Pseudomonas aeruginosa) and Mycobacterium tuberculosis
(H37Rv).
PMID- 25847770
TI - Structure-activity relationship and properties optimization of a series of
quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway.
AB - Wnt signaling pathway plays a critical role in numerous cellular processes,
including tumor initiation, proliferation, invasion/infiltration, metastasis
formation and resistance to chemotherapy. In a drug discovery project aimed at
the identification of inhibitors of the canonical Wnt pathway, we selected a
series of quinazoline 2,4-diones as starting point for the therapeutic treatment
of glioblastoma multiforme. Despite of poor physico-chemical properties of hit
compound 1, our medicinal chemistry effort allowed the discovery and
characterization of lead compound 33 (SEN461), with improved ADME profile, good
bioavailability and active in vitro and in vivo in glioblastoma, gastric and
sarcoma tumors.
PMID- 25847771
TI - Towards small molecule inhibitors of mono-ADP-ribosyltransferases.
AB - Protein ADP-ribosylation is a post-translational modification involved in DNA
repair, protein degradation, transcription regulation, and epigenetic events.
Intracellular ADP-ribosylation is catalyzed predominantly by ADP
ribosyltransferases with diphtheria toxin homology (ARTDs). The most prominent
member of the ARTD family, poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) has been a
target for cancer drug development for decades. Current PARP inhibitors are
generally non-selective, and inhibit the mono-ADP-ribosyltransferases with low
potency. Here we describe the synthesis of acylated amino benzamides and
screening against the mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14,
ARTD10/PARP10, and the poly-ADP-ribosyltransferase ARTD1/PARP1. The most potent
compound inhibits ARTD10 with sub-micromolar IC50.
PMID- 25847772
TI - Acupuncture treatment modulates the resting-state functional connectivity of
brain regions in migraine patients without aura.
AB - OBJECTIVE: To investigate the modulatory effect of acupuncture treatment on the
resting-state functional connectivity of brain regions in migraine without aura
(MWoA) patients. METHODS: Twelve MWoA patients were treated with standard
acupuncture treatment for 4 weeks. All MWoA patients received resting-state
functional magnetic resonance imaging (fMRI) scanning before and after
acupuncture treatment. Another 12 normal subjects matched in age and gender were
recruited to serve as healthy controls. The changes of restingstate functional
connectivity in MWoA patients before and after the acupuncture treatment and
those with the healthy controls were compared. RESULTS: Before acupuncture
treatment, the MWoA patients had significantly decreased functional connectivity
in certain brain regions within the frontal and temporal lobe when compared with
the healthy controls. After acupuncture treatment, brain regions showing
decreased functional connectivity revealed significant reduction in MWoA patients
compared with before acupuncture treatment. CONCLUSIONS: Acupuncture treatment
could increase the functional connectivity of brain regions in the intrinsic
decreased brain networks in MWoA patients. The results provided further insights
into the interpretation of neural mechanisms of acupuncture treatment for
migraine.
PMID- 25847773
TI - Extract of Zuojin Pill ([characters: see text]) induces apoptosis of SGC-7901
cells via mitochondria-dependent pathway.
AB - OBJECTIVE: To observe the effects of water extract of Zuojin Pill ([characters:
see text], ZJP) on inhibiting the growth of human gastric cancer cell line SGC
7901 and its potential mechanism. METHODS: Effects of ZJP on SGC-7901 cells
growth were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H
tetrazolium bromide (MTT) assay, cell apoptosis and cell cycle were determined by
flow cytometry, and apoptosis induction was detected by means of DNA gel
electrophoresis. The cellular mechanism of drug-induced cell death was unraveled
by assaying oxidative injury level of SGC-7901 cell, mitochondrial membrane
potentials, expression of apoptosis-related genes, such as B cell
lymphoma/lewkmia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cleaved caspase
3 and caspase-9. RESULTS: ZJP exerted evident inhibitory effect on SGC-7901 cells
by activating production of reactive oxygen species and elevating Bax/Bcl-2 ratio
in SGC-7901 cells, leading to attenuation of mitochondrial membrane potential and
DNA fragmentation. CONCLUSIONS: ZJP inhibits the cancer cell growth via
activating mitochondria-dependent apoptosis pathway. ZJP can potentially serve as
an antitumor agent.
PMID- 25847774
TI - Electroacupuncture attenuates spinal nerve ligation-induced microglial activation
mediated by p38 mitogen-activated protein kinase.
AB - OBJECTIVE: To investigate whether analgesic effect of electroacupuncture (EA) is
affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia.
METHODS: There were two experiments. The experiment 1: 40 male Sprague-Dawley
(SD) rats were randomly divided into the normal, surgery, EA and sham EA groups,
and the L5 spinal nerve ligation (SNL) on the right side was used to establish
neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun
(BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal
thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73
h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of
microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in
bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence,
respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced
neuropathic pain, and then were randomly divided into the dimethyl sulfoxide
(DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)
1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was
administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH
were measured as mentioned above. RESULTS: SNL-induced neuropathic pain reduced
PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar
SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our
study. EA treatment significantly alleviated SNL-mediated mechanical
hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar
SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no
influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42
positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580
synergistically increased PWTs, and reduced the expression of bilateral spinal OX
42 (P<0.01 or P<0.05). CONCLUSIONS: The central mechanism of EA-induced anti
hyperalgesia may be partially associated with the reduced expression of p-p38
MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain.
Therefore, EA may be a new complementary and alternative therapy for neuropathic
pain.
PMID- 25847775
TI - Effect of Huanshuai Recipe Oral Liquid ([characters: see text]) on renal
dysfunction progression in patients with atherosclerotic renal artery stenosis.
AB - OBJECTIVE: To investigate the effect of Huanshuai Recipe Oral Liquid
([characters: see text], HSR) on retarding the progression of renal dysfunction
in patients with atherosclerotic renal artery stenosis (ARAS). METHODS: A total
of 52 ARAS patients with the Chinese medicine (CM) syndrome of qi deficiency and
blood stasis, phlegm and dampness retention were recruited and randomly assigned
into the treatment group (36 cases) and the control group (16 cases). Both groups
received a basic treatment (high-quality low-protein diet, blood pressure
control, lipid-lowering, correcting the acidosis, etc.). In addition, the
treatment group received 20 mL HSR and the control group received placebo, 3
times a day for 6 months. Renal function (serum creatinine, blood urea nitrogen
and uric acid) and blood lipids (cholesterol, triglycerides and low density
lipoprotein) were examined monthly. The estimated glomerular filtration rate
(eGFR) and CM syndrome score were compared between groups. RESULTS: After
treatment, compared with the control group, the serum creatinine level, uric acid
level and CM syndrome score of the treatment group were significantly decreased
(P<0.05 or P<0.01), and the eGFR in the treatment group were significantly
increased (P<0.05). CONCLUSION: HSR can effectively improve the renal function
and clinical symptoms of ARAS patients.
PMID- 25847776
TI - Wendan decoction (???) for treatment of schizophrenia: a systematic review of
randomized controlled trials.
AB - OBJECTIVE: To assess the beneficial and adverse effects of Wendan Decoction (???,
WDD) for the treatment of schizophrenia. METHODS: Five electronic databases were
searched until May 2014, including the Chinese National Knowledge Infrastructure,
the Chinese Biomedical Literature Database, the Chinese Scientist Journal
Database, PubMed, and the Cochrane Central Register of Controlled Trials in the
Cochrane Library. The randomized controlled trials (RCTs) testing WDD against
placebo, antipsychotic drugs, or WDD combined with antipsychotic drugs against
antipsychotic drugs alone were included. Study selection, data extraction,
quality assessment, and data analyses were conducted according to the Cochrane
standards. RESULTS: Thirteen RCTs (involving 1,174 patients) were included and
the methodological quality was evaluated as generally low. The pooled results
showed that WDD combined with antipsychotic drugs were more effective in clinical
comprehensive effect, Positive and Negative Syndrome Scale (PANSS) scores and
Brief Psychiatric Rating Scale scores compared with antipsychotic drugs alone.
However, WDD had less effectiveness compared with antipsychotics in clinical
comprehensive effect; and WDD was not different from antipsychotic drugs for
PANSS scores. The side effects were significantly reduced in the intervention
group compared with the control group. CONCLUSIONS: WDD appears to be effective
on improving symptoms in patients with schizophrenia. However, due to poor
methodological quality in the majority of the included trials, the potential
benefit from WDD needs to be confirmed in rigorous trials and the design and
reporting of trials should follow the international standards.
PMID- 25847777
TI - Protective effects of Radix Astragali injection on multiple organs of rats with
obstructive jaundice.
AB - OBJECTIVE: To investigate the protective effects and mechanisms of Radix
Astragali Injection on multiple organs of rats with obstructive jaundice (OJ).
METHODS: A total of 180 rats were randomly divided into the sham-operated, model
control and treated groups (60 in each group). On 7, 14, 21 and 28 days after
operation, the serum contents of alanine aminotransferase (ALT), aspartate
aminotransferase (AST), r-glutamyl transpeptidase (r-GT), total bilirubin (TBil),
direct bilirubin (DBil), blood urine nitrogen (BUN), and creatinine (CREA) were
determined. And the pathological changes of livers, kidneys and lungs, and
protein expressions of toll-like receptor-4 (TLR-4) of livers, intercellular
adhesion molecule-1 (ICAM-1) of lungs, Bax and nuclear factor-kappa B (NF
kappaB), as well as apoptotic indexes of multiple organs were observed,
respectively. RESULTS: The pathological severity scores of multiple organs
(including livers on 7, 14, 21 and 28 days, kidneys on 14 and 28 days, and lungs
on 14 days), serum contents of ALT (14 and 21 days), AST (14 days), TBil (7, 14,
21 and 28 days), DBil (14 and 21 days), BUN (28 days), protein expressions of TLR
4 (in livers, 28 days), Bax (in livers and kidneys, 21 days), and apoptotic
indexes in livers (7 and 21 days) in the treated group were significantly lower
than those in the model control group (P<0.05 or P<0.01). CONCLUSION: Radix
Astragali Injection exerts protective effects on multiple organs of OJ rats by
improving the pathological changes of lung, liver and kidney, decreasing the
serum index of hepatic and renal function as well as inhibiting the protein
expression of TLR-4 and Bax in the livers and Bax in the kidneys.
PMID- 25847778
TI - Comparison of electroacupuncture and moxibustion on brain-gut function in
patients with diarrhea-predominant irritable bowel syndrome: A randomized
controlled trial.
AB - OBJECTIVE: To compare the effects of electroacupuncture (EA) and moxibustion
therapies on patients with diarrhea-predominant irritable bowel syndrome (D-IBS).
METHODS: A total of 60 D-IBS patients were randomly allocated to the EA group (30
cases) and moxibustion group (30 cases). Before and after treatment, the
gastrointestinal symptoms and psychological symptoms were scored by Visual
Analogue Scale, Bristol Stool Form Scale, Hamilton Anxiety Rating Scale (HAMA),
and Hamilton Depression Rating Scale (HAMD); the expressions of 5
hydroxytryptamine (5-HT), 5-HT3 receptor (5-HT3R), and 5-HT4 receptor (5-HT4R) in
the sigmoid mucosal tissue were measured by immunohistochemical staining.
Additionally, the effects on the functional brain areas of the anterior cingulate
cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by
functional magnetic resonance imaging. RESULTS: Compared with before treatment,
both EA and moxibustion groups reported significant improvements in abdominal
pain and abdominal bloating after treatment (P<0.01 or P<0.05). The moxibustion
group reported greater improvements in defecation emergency, defecation
frequency, and stool feature than the EA group (P<0.01). Both HAMA and HAMD
scores were significantly decreased in the moxibustion group than in the EA group
(P<0.01). Both groups demonstrated significantly reduced expressions of 5-HT, 5
HT3R and 5-HT4R in the colonic mucosa after treatment (P<0.01), with a greater
reduction of 5-HT in the moxibustion group (P<0.05). Finally, decreased activated
voxel values were observed in the left IC, right IC and PFC brain regions of
patients in the moxibustion group under stimulation with 150 mL colorectal
distension after treatment (P<0.05 or P<0.01), while in the EA group only PFC
area demonstrated a reduction (P<0.05). CONCLUSION: Moxibustion can significantly
improve the symptoms of D-IBS, suggesting that moxibustion may be a more
effective therapy than EA for D-IBS patients.
PMID- 25847779
TI - Xuezhikang () reduced renal cell apoptosis in streptozocin-induced diabetic rats
through regulation of Bcl-2 family.
AB - OBJECTIVE: To investigate the effect of Xuezhikang (, XZK) on renal cell
apoptosis in diabetic rats and the possible mechanism. METHODS: Sixty-six rats
were randomly divided into 3 groups: the normal, model and XZK groups. In each
group, the rats were further randomly divided into 3-month and 6-month subgroups,
respectively. Diabetes of rats was induced by a single intraperitoneal injection
of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received
gastric perfusion of XZK (1200 mg/kg body weight) everyday for 3 or 6 months,
while rats in the normal and model groups received equal volume of saline. Twenty
four hours' urine was collected for urinary albumin excretion (UAE) measurement.
Periodic acid-Schiff (PAS) and Masson's trichrome staining were used for
saccharides and collagen detection. Cell apoptosis of renal cortex was
investigated by TdT-mediated dUTP nick end labeling (TUNEL) staining. Bax and Bcl
2 expressions were detected by immunohistochemistry and Western blot,
respectively. Cytochrome C (Cyt C) and caspase-9 concentration were detected by
Western blot. RESULTS: Compared with the model group, XZK treatment could
significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell
apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as
suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to
the suppression of Bax/Bcl-2 ratio at 3 and 6 months (P<0.05 or P<0.01).
Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides
and Masson's trichromestained collagen to different extent. CONCLUSIONS: Renal
cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic
pathway might be involved. XZK treatment could attenuate pathological changes in
diabetic kidney and reduce renal cell apoptosis, probably via the suppression of
Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase
9 activation.
PMID- 25847780
TI - Phytopharmacological Profile of Jasminum grandiflorum Linn. (Oleaceae).
AB - Plants are the real basis towards animal life and are also central to people's
livelihood. The contributions of the plants in performing varied religious
celebrations and in other multiple beneficiaries like medicine, human happiness
as well as in treating deadly diseases can never be neglected. In treating
diseases, the plants and their constituents are better choice than any other
synthetic chemical. The nature has been kind enough to provide the human beings
with various types of medicinal plants and in the real sense these form the
storehouse of curing almost all the ailments. Consequently, most of the drugs
which are being used in preparing formulations have their origin and roots in the
plants which form the chief natural source of medicines. Even in modern era, the
plant-derived drugs are being extensively used, either in their original or semi
synthetic form. It is because their natural phytoconstituents are highly
innocuous posing relatively fewer or no side effects. Based upon their
observations, analysis and experience, our ancestors used many plants for
medicinal purposes and thus their efforts need to be supported by scientific
evidence. Jasminum grandiflorum Linn. is one of such important plants. It has
been extensively used by the tribes all over India to treat different diseases
which mainly include body pains, toothache, stomach ache, ulcers, and sexual
impotency. Chemistry of the plant revealed the presence of mainly secoiridoids,
terpenoids, flavonoids and tannins. Not much scientific support was given to the
folklore claims for this plant but some of its traditional uses were investigated
like spasmolytic, wound healing, antimicrobial, angiotensin converting enzyme
inhibitor, antiulcer and antioxidant activities. This article is the review of
research works done on the plant Jasminum grandiflorum Linn. to date. As a part
of it the local names, morphology, traditional claims, chemistry and
pharmacological activities have been discussed.
PMID- 25847781
TI - Palladium-catalyzed hydrocarboxylation of alkynes with formic acid.
AB - A palladium-catalyzed hydrocarboxylation of alkynes with formic acid has been
developed. The method provides acrylic acid and derivatives in good yields with
high regioselectivity without the need to handle toxic CO gas.
PMID- 25847783
TI - A SEM, EDS and vibrational spectroscopic study of the tellurite mineral:
Sonoraite Fe(3+)Te(4+)O3(OH).H2O.
AB - We have undertaken a study of the tellurite mineral sonorite using electron
microscopy with EDX combined with vibrational spectroscopy. Chemical analysis
shows a homogeneous composition, with predominance of Te, Fe, Ce and In with
minor amounts of S. Raman spectroscopy has been used to study the mineral
sonoraite an examples of group A(XO3), with hydroxyl and water units in the
mineral structure. The free tellurite ion has C3v symmetry and four modes, 2A1
and 2E. An intense Raman band at 734 cm(-1) is assigned to the nu1 (TeO3)(2-)
symmetric stretching mode. A band at 636 cm(-1) is assigned to the nu3 (TeO3)(2-)
antisymmetric stretching mode. Bands at 350 and 373 cm(-1) and the two bands at
425 and 438 cm(-1) are assigned to the (TeOv)(2-)nu2 (A1) bending mode and
(TeO3)(2-)nu4 (E) bending modes. The sharp band at 3283 cm(-1) assigned to the OH
stretching vibration of the OH units is superimposed upon a broader spectral
profile with Raman bands at 3215, 3302, 3349 and 3415 cm(-1) are attributed to
water stretching bands. The techniques of Raman and infrared spectroscopy are
excellent for the study of tellurite minerals.
PMID- 25847782
TI - Inhibition of farnesyl pyrophosphate synthase attenuates angiotensin II-induced
fibrotic responses in vascular smooth muscle cells.
AB - Through the regulation of the RhoA/Rho kinase (ROCK) pathway, angiotensin II (Ang
II)-induced fibrotic responses contribute to vascular remodeling. Farnesyl
pyrophosphate synthase (FPPS) plays an important role in cardiovascular
remodeling through the modulation of the above-mentioned pathway. However, the
role of FPPS in Ang II-induced fibrotic responses and the related molecular
mechanisms have not yet been elucidated. In the present study, vascular smooth
muscle cells (VSMCs) from Sprague-Dawley (SD) rats were stimulated with Ang II.
Cell proliferation was measusred usin the cell counting kit-8 (CCK-8). The levels
of connective tissue growth factor (CTGF), FPPS, and those of phosphorylated and
total extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal
kinase (JNK) were determined by western blot analysis. RhoA activity was
determined using a pull-down assay. The results revealed that stimulation with
Ang II enhanced cell proliferation, and increased the protein expression levels
of FPPS and CTGF in the VSMCs. The inhibition of FPPS with ibandronate sodium
attenuated the Ang II-induced increase in cell proliferation, CTGF expresison and
RhoA activity; these effects were partially reversed by treatment with
geranylgeraniol and were mimicked by GGTI-286. Furthermore, both SB203580 (a
specific inhibitor of p38) and SP600125 (JNK1, JNK2 and JNK3 inhibitor)
diminished the Ang II-induced production of CTGF; however, the inhibition of FPPS
reduced the Ang II-induced activation of p38 mitogen-activated protein kinase
(MAPK) and JNK. In conclusion, our data indicate that FPPS may play an important
role in Ang II-induced fibrotic responses in VSMCs, and the underlying mechanisms
at least partly involve the modulation of RhoA activity, and the p38 and JNK
pathways.
PMID- 25847784
TI - A SEM, EDS and vibrational spectroscopic study of the clay mineral fraipontite.
AB - The mineral fraipontite has been studied by using a combination of scanning
electron microscopy with energy dispersive analysis and vibrational spectroscopy
(infrared and Raman). Fraipontite is a member of the 1:1 clay minerals of the
kaolinite-serpentine group. The mineral contains Zn and Cu and is of formula
(Cu,Zn,Al)3(Si,Al)2O5(OH)4. Qualitative chemical analysis of fraipontite shows an
aluminium silicate mineral with amounts of Cu and Zn. This kaolinite type mineral
has been characterised by Raman and infrared spectroscopy; in this way aspects
about the molecular structure of fraipontite clay are elucidated.
PMID- 25847785
TI - Vibrational spectra, NLO analysis, and HOMO-LUMO studies of 2-chloro-6
fluorobenzoic acid and 3,4-dichlorobenzoic acid by density functional method.
AB - The FTIR and FT-Raman spectra of 2-chloro-6-fluorobenzoic acid and 3,4
dichlorobenzoic acid have been recorded in the region 4000-400 cm(-1) and 3500-50
cm(-1), respectively. Utilizing the observed FTIR and FT-Raman data, a complete
vibrational assignment and analysis of fundamental modes of the compounds were
carried out. The optimized molecular geometries, vibrational frequencies,
thermodynamic properties and atomic charge of the compounds were calculated by
using density functional theory (B3LYP) method with 6-311+G and 6-311++G basis
sets. The difference between the observed and scaled wave number values of most
of fundamentals is very small. Unambiguous vibration assignment of all the
fundamentals is made up the total energy distribution (TED). The calculated HOMO
and LUMO energies show that charge transfer occurs within the molecules. Besides,
molecular electro static potential (MESP), Mulliken's charge analysis, first
order hyper polarizability and several thermodynamic properties were performed by
the DFT method.
PMID- 25847786
TI - Complementary analysis of tissue homogenates composition obtained by Vis and NIR
laser excitations and Raman spectroscopy.
AB - Raman spectroscopy and four excitation lines in the visible (Vis: 488, 532, 633
nm) and near infrared (NIR: 785 nm) were used for biochemical analysis of rat
tissue homogenates, i.e. myocardium, brain, liver, lung, intestine, and kidney.
The Vis Raman spectra are very similar for some organs (brain/intestines and
kidney/liver) and dominated by heme signals when tissues of lung and myocardium
were investigated (especially with 532 nm excitation). On the other hand, the NIR
Raman spectra are specific for each tissue and more informative than the
corresponding ones collected with the Vis excitations. The spectra analyzed
without any special pre-processing clearly illustrate different chemical
composition of each tissue and give information about main components e.g. lipids
or proteins, but also about the content of some specific compounds such as amino
acid residues, nucleotides and nucleobases. However, in order to obtain the whole
spectral information about tissues complex composition the spectra of Vis and NIR
excitations should be collected and analyzed together. A good agreement of data
gathered from Raman spectra of the homogenates and those obtained previously from
Raman imaging of the tissue cross-sections indicates that the presented here
approach can be a method of choice for an investigation of biochemical variation
in animal tissues. Moreover, the Raman spectral profile of tissue homogenates is
specific enough to be used for an investigation of potential pathological changes
the organism undergoes, in particular when supported by the complementary FTIR
spectroscopy.
PMID- 25847787
TI - Novel spectrophotometric method for selective determination of compounds in
ternary mixtures (dual wavelength in ratio spectra).
AB - A simple selective spectrophotometric method for determination of compounds in
ternary mixture was developed by combining the resolution power of two well-known
methods that are commonly used for binary mixtures; namely ratio difference
method and dual wavelength. The new method (dual wavelength in ratio spectra) was
successfully applied for the determination of a ternary mixture of betamethasone
dipropionate (BM), clotrimazole (CT) and benzyl alcohol (BA) in pure powder form
and in their pharmaceutical preparation. The difference in amplitudes (DeltaP) in
the ratio spectra at 252.0 and 258.0 nm (DeltaP(252.0-258.0 nm)) corresponds to
BM, while DeltaP(266.8-255.4 nm) and DeltaP(254.2-243.5 nm) corresponds to CT and
BA, respectively. The method was validated as per the USP 2005 guidelines. The
developed method can be used in quality control laboratories for routine analysis
of compounds in ternary mixtures.
PMID- 25847788
TI - An abiotic receptor and its Cu(II) complex as selective 'turn-off' chemosensor
for bisulfate ion.
AB - The ligand 2,6-bis[(N-phenyl)amido]-4-methylphenol (receptor 1) and its
copper(II) complex (receptor 2) having amide moiety have been designed and
synthesized for selective sensing of anions. The anion recognition behavior of
the receptor 1 and its copper complex (receptor 2) has been studied in
acetonitrile. Quenching of fluorescence was observed for both receptors in
presence of HSO4(-) anion whereas other physiologically and environmentally
important anions such as F(-), Cl(-), Br(-), I(-), CN(-), OAc(-), HCO3(-), H2PO4(
), NO3(-), NO2(-) and SO4(2-) show fluorescence enhancement behavior. The sensing
protocol has been studied both spectrophotometrically as well as
spectrofluorometrically. Fluorescence quenching is suggested to proceed via both
dynamic and static processes.
PMID- 25847789
TI - Self-assembled supramolecular structure of 1-methyl piperazinium 4-nitrophenolate
4-nitrophenol monohydrate single crystal: Synthesis, growth, thermal and photo
physical properties.
AB - A new photoactive organic crystal, 1-methyl piperazinium 4-nitrophenolate-4
nitrophenol monohydrate (MP4NPM) has been synthesised at 35 degrees C. Good
quality single crystals of MP4NPM have successfully been grown by slow
evaporation solution growth technique. Single crystal X-ray diffraction analysis
shows that MP4NPM belongs to monoclinic crystal system with space group P21/n.
The molecular structure was further confirmed by modern spectroscopic techniques
like FT-NMR (both 1D and 2D), FT-IR, UV-Vis-NIR and fluorescence. The UV-Vis-NIR
spectrum was performed to understand the range of optical transparency and the
results showed its suitability for nonlinear optical applications. Fluorescence
emission revealed that MP4NPM can serve as a photo active material. Thermal
properties of MP4NPM were investigated using simultaneous TG-DSC analysis.
Frequency and temperature dependent dielectric properties were studied in the
frequency range 500 Hz-5 MHz and 40-50 degrees C, respectively. Vicker's
microhardness measurements revealed that MP4NPM belongs to the category of soft
material. Kurtz and Perry powder technique shows that MP4NPM has SHG efficiency
0.89 times that of potassium dihydrogen phosphate (KDP).
PMID- 25847790
TI - Enhanced ultraviolet fluorescence in surface modified ZnO nanostructures: Effect
of PANI.
AB - ZnO:polyaniline nanocomposite (ZnO:PANI) films were prepared and their steady
state fluorescence and time resolved photoluminescence properties were discussed.
X-ray diffraction and infrared spectroscopy analyses confirmed the interaction
and formation of ZnO:PANI composite films. Optical absorption spectrum of pure
PANI showed two bands at 325 and 625 nm which were ascribed to pi->pi(*)
transition in the benzoid and exciton formation in the quinoid rings,
respectively. Pure ZnO nanoparticles exhibited a band at 369 nm was due to their
exciton absorption and the composite films showed a broad band in the visible
region and small intensity band at the UV region. Fluorescence spectra showed
that the ultra violet emission of ZnO was enhanced about tenfold due to the
electron transfer from PANI to ZnO nanoparticles and the suppression of visible
emission was attributed to the surface passivation effect. The transfer of
electron from PANI to ZnO and its decay dynamics were experimentally analyzed
through time resolved fluorescence measurements.
PMID- 25847791
TI - A surface-enhanced Raman study of N-methylquinolinium tricyanoquinodimethanide
adsorbed on Ag nanospheres: Determination of molecular orientation and order.
AB - Quinolinium tricyanoquinodimethanides are among the most promising molecules for
electronic applications. Disorder can be detrimental to the desired electronic
properties of a monolayer, and as such, a reliable method to characterize a
monolayer without destroying or creating defects is paramount to determining
potential applications. Here, the normal and surface-enhanced Raman scattering
spectra of N-methylquinolinium tricyanoquinodimethanide (CH3Q-3CNQ) on silver
coated nanosurfaces have been obtained and analyzed. Theoretical treatment of
CH3Q-3CNQ was performed. Optimization and frequency search was conducted using
the B3LYP functional with the 6-31G(d) basis set. A complete list of frequencies
and assignments for the molecules are presented. The spectroscopic evidence
points to the fact that a monolayer of CH3Q-3CNQ can be formed through the self
assembly process, and the SERS data indicate that the monolayer attaches to the
silver surface through the nitrile groups.
PMID- 25847792
TI - Quantitative determination of isoquinoline alkaloids and chlorogenic acid in
Berberis species using ultra high performance liquid chromatography with hybrid
triple quadrupole linear ion trap mass spectrometry.
AB - Berberis species are well known and used extensively as medicinal plants in
traditional medicine. They have many medicinal values attributable to the
presence of alkaloids having different pharmacological activities. In this study,
a method was developed and validated as per international conference on
harmonization guidelines using ultra high performance liquid chromatography with
hybrid triple quadrupole-linear ion trap mass spectrometry operated in the
multiple reaction monitoring mode for nine bioactive compounds, including
protoberberine alkaloids, aporphine alkaloids and chlorogenic acid. This method
was applied in different plant parts of eight Berberis species to determine
variations in content of nine bioactive compounds. The separation was achieved on
an ACQUITY UPLC CSHTM C18 column using a gradient mobile phase at flow rate 0.3
mL/min. Calibration curves for all the nine analytes provided optimum linear
detector response (with R(2) >=0.9989) over the concentration range of 0.5-1000
ng/mL. The precision and accuracy were within RSDs <=2.4 and <=2.3%,
respectively. The results indicated significant variation in the total contents
of the nine compounds in Berberis species.
PMID- 25847794
TI - From isolated 1H-pyrazole cryptand anion receptors to hybrid inorganic-organic 1D
helical polymeric anion receptors.
AB - We report a novel 1-D helical coordination polymer formed by protonated polyamine
1H-pyrazole cryptands interconnected by Cu(2+) metal ions that are able to
encapsulate anionic species behaving as a multianion receptor. Switching from a
monomeric receptor to a polymeric receptor is activated by metal ions and pH.
PMID- 25847793
TI - Intralesional tuberculin (PPD) versus measles, mumps, rubella (MMR) vaccine in
treatment of multiple warts: a comparative clinical and immunological study.
AB - Intralesional purified protein derivative (PPD) or mumps, measles, rubella (MMR)
were not previously compared regarding their efficacy or mechanism of action in
treatment of warts. We aimed to compare their efficacy in treatment of multiple
warts and investigate their effect on serum interleukin (IL)-4 and IL-12. Thirty
patients with multiple warts were included (10 treated with PPD, 10 with MMR, and
10 with normal saline (control)). Injection was done every 3 weeks until
clearance or maximum of three treatments. Clinical response of target and distant
warts was evaluated. Serum ILs-4 and -12 were assessed before and after
treatment. A significantly higher rate of complete response was found in target
and distant warts with PPD (60% each) and MMR (80%, 40%, respectively) compared
with controls (0%), with no significant difference between both treatments. After
treatment, the control group showed the lowest serum IL-12 and IL-4 levels
compared with the MMR- and PPD-treated groups with statistically significant
difference in between. MMR resulted in a significantly higher serum IL-12 than
PPD. With PPD, IL-4 was increased with statistically significant change compared
with pretreat-ment level. Intralesional PPD and MMR show comparable efficacy and
safety in treatment of multiple warts. Serum ILs-4 and-12 increase following
antigen injection.
PMID- 25847795
TI - Biomass and lipid production of a local isolate Chlorella sorokiniana under
mixotrophic growth conditions.
AB - A local Chlorella sp. isolate with 97% rbcL sequence identity to Chlorella
sorokiniana was evaluated in terms of its biomass and lipid production under
mixotrophic growth conditions. Glucose-supplemented cultures exhibited increasing
growth rate and biomass yield with increasing glucose concentration. Highest
growth rate and biomass yield of 1.602 day(-1) and 687.5 mg L(-1), respectively,
were achieved under 2 g L(-1) glucose. Nitrogen starvation up to 75% in the 1.0 g
L(-1) glucose-supplemented culture was done to induce lipid accumulation and did
not significantly affect the growth. Lipid content ranges from 20% to 27% dry
weight. Nile Red staining showed more prominent neutral lipid bodies in starved
mixotrophic cultures. C. sorokiniana exhibited enhanced biomass production under
mixotrophy and more prominent neutral lipid accumulation under nitrogen
starvation with no significant decrease in growth; hence, this isolate could be
further studied to establish its potential for biodiesel production.
PMID- 25847796
TI - Learning to care at the end.
PMID- 25847797
TI - Cow's Milk Contamination of Human Milk Purchased via the Internet.
AB - BACKGROUND: The US Food and Drug Administration recommends against feeding
infants human milk from unscreened donors, but sharing milk via the Internet is
growing in popularity. Recipient infants risk the possibility of consuming
contaminated or adulterated milk. Our objective was to test milk advertised for
sale online as human milk to verify its human origin and to rule out
contamination with cow's milk. METHODS: We anonymously purchased 102 samples
advertised as human milk online. DNA was extracted from 200 MUL of each sample.
The presence of human or bovine mitochondrial DNA was assessed with a species
specific real-time polymerase chain reaction assay targeting the nicotinamide
adenine dinucleotide (NADH) dehydrogenase subunit 5 gene. Four laboratory-created
mixtures representing various dilutions of human milk with fluid cow's milk or
reconstituted infant formula were compared with the Internet samples to
semiquantitate the extent of contamination with cow's milk. RESULTS: All Internet
samples amplified human DNA. After 2 rounds of testing, 11 samples also contained
bovine DNA. Ten of these samples had a level of bovine DNA consistent with human
milk mixed with at least 10% fluid cow's milk. CONCLUSIONS: Ten Internet samples
had bovine DNA concentrations high enough to rule out minor contamination,
suggesting a cow's milk product was added. Cow's milk can be problematic for
infants with allergy or intolerance. Because buyers cannot verify the composition
of milk they purchase, all should be aware that it might be adulterated with
cow's milk. Pediatricians should be aware of the online market for human milk and
the potential risks.
PMID- 25847798
TI - Prevent youth assault by assaulting firearm violence.
PMID- 25847799
TI - Two Case Reports of Successful Treatment of Cholestasis With Steroids in Patients
With PFIC-2.
AB - Mutations in the gene encoding the canalicular bile salt export pump (BSEP) can
result in progressive familial intrahepatic cholestasis type 2 (PFIC-2).
Treatment options are limited, and PFIC-2 often necessitates liver
transplantation. We report on a young woman and a boy who clinically presented
with PFIC-2 phenotypes and dramatically improved with steroid treatment. Gene
sequencing of ABCB11 encoding for BSEP revealed 2 relevant mutations in both
patients. The young woman was compound heterozygous for p.T919del and p.R1235X.
At the age of 5 years, partial biliary diversion was performed and rescued liver
function but left serum bile salt levels elevated. At age 23 she developed
systemic lupus erythematosus. Unexpectedly, steroid therapy normalized serum bile
salt levels, with a strong correlation with the steroid dose. She is currently in
clinical remission. The boy was compound heterozygous for the ABCB11 mutations
c.150+3A>C and p.R832C and presented with intractable pruritus. When he developed
colitis, he was treated with steroids. The pruritus completely disappeared and
relapsed when steroids were withdrawn. To date, with low-dose budesonide, the boy
has been symptom-free for >3 years. In conclusion, the clinical courses suggest
that patients with BSEP deficiency and residual BSEP activity may benefit from
steroid-based therapy, which represents a new treatment option.
PMID- 25847800
TI - Competency in neonatal endotracheal intubation: mission impossible?
PMID- 25847801
TI - Parental hope for children with advanced cancer.
AB - BACKGROUND: Previous work suggests that parents of children with cancer can
remain hopeful despite receiving prognostic information, but we know little about
what hope means to such parents, or the extent to which parents can feel hopeful
even while facing the child's impending death. METHODS: We audiotaped
conversations between clinicians and parents of 32 children with relapsed or
refractory cancer, and then interviewed parents about their hopes and
expectations for their child. RESULTS: Parent statements about prognosis in
interviews mirrored those made by clinicians during discussions about the child's
diagnosis with refractory or relapsed cancer. Clinicians used language referring
to hope during these conversations but did not ask parents directly about their
hopes. Parents expressed a range of hopes for their children, from hopes related
to cure or treatment response, to quality of life, normalcy, and love and
relationships for the child. For most parents, expectations about prognosis were
not aligned with their hopes for the child; for example, many parents hoped for a
cure and also reported that they did not believe cure was possible. Many parents
were able to acknowledge this incongruence. CONCLUSIONS: Parents accurately
conveyed the reality of their child's serious condition in the setting of
advanced cancer, and yet maintained hope. Hopes were not limited to hope for
cure/treatment response. Clinicians should be encouraged to engage in direct
conversations about hope with parents as a means to elicit realistic hopes that
can help to focus the most meaningful plans for the child and family.
PMID- 25847802
TI - Two infants, same prognosis, different parental preferences.
AB - A central principle of justice is that similar cases should be decided in similar
ways. In pediatrics, however, there are cases in which 2 infants have similar
diagnoses and prognoses, but their parents request different treatments. In this
Ethics Rounds, we present such a situation that occurred in a single NICU. Three
physician-ethicists analyze the issues.
PMID- 25847803
TI - Nicotine replacement therapy in pregnancy and major congenital anomalies in
offspring.
AB - BACKGROUND AND OBJECTIVES: Nicotine replacement therapy (NRT) is now being used
as a smoking cessation aid during pregnancy, although little is known about fetal
safety. We assessed the relationship between early pregnancy exposure to NRT or
smoking with major congenital anomalies (MCA) in offspring. METHODS: We studied
192,498 children born in the United Kingdom between 2001 and 2012 with linked
mother-child primary care records. The absolute risks of MCAs in the NRT group
(women prescribed NRT during the first trimester or 1 month before conception
[and therefore likely consumed during the first trimester]) and odds ratios (ORs)
and 99% confidence intervals (CIs) were compared with those of women who smoked
during pregnancy and with a control group (women who neither smoked nor were
prescribed NRT); logistic regression models adjusted for maternal morbidities
that increase MCA risk were used for analysis. RESULTS: MCA prevalence was 288
per 10,000 live births (5535 children with >= 1 MCA). Maternal morbidities were
most common in the NRT group (35%) followed by smokers (27%) and the control
group (20%). Compared with the control group, adjusted ORs for MCAs in the NRT
group and smokers were 1.12 (99% CI: 0.84-1.48) and 1.05 (99% CI: 0.89-1.23),
respectively. The OR comparing the NRT group directly with smokers was 1.07 (99%
CI: 0.78-1.47). There were no statistically significant associations between
maternal NRT and system-specific anomalies except for respiratory anomalies (OR:
4.65 [99% CI: 1.76-12.25]; absolute risk difference: 3 per 1000 births), which
was based on 10 exposed cases. CONCLUSIONS: For most system-specific MCAs, we
found no statistically significant increased risks associated with maternal NRT
prescribed during pregnancy, except for respiratory anomalies. Although this
study is the largest published to date, NRT use in pregnancy remains rare; thus,
the statistical power was limited. Higher morbidities in those women prescribed
NRT may also be an explanatory factor. Nevertheless, absolute MCA risks were
similar between women who smoked and those prescribed NRT during pregnancy.
PMID- 25847804
TI - Validity of the strengths and difficulties questionnaire in preschool-aged
children.
AB - BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) is widely used to
screen for child mental health problems and measure common forms of
psychopathology in 4- to 16-year-olds. Using longitudinal data, we examined the
validity of a version adapted for 3- to 4-year-olds. METHODS: We used SDQ data
from 16,659 families collected by the Millennium Cohort Study, which charts the
development of children born throughout the United Kingdom during 2000-2001.
Parents completed the preschool SDQ when children were aged 3 and the standard
SDQ at ages 5 and 7. The SDQ's internal factor structure was assessed by using
confirmatory factor analysis, with a series of competing models and extensions
used to determine construct, convergent, and discriminant validity and
measurement invariance over time. Predictive validity was evaluated by examining
the relationships of age 3 SDQ scores with age 5 diagnostic measures of attention
deficit/hyperactivity disorder, autism spectrum disorder/Asperger syndrome, and
teacher-reported measures of personal, social, and emotional development.
RESULTS: Confirmatory factor analysis supported a 5-factor measurement model.
Internal reliability of subscales ranged from omega = 0.66 (peer problems) to
omega = 0.83 (hyperactivity). Item-factor structures revealed measurement
invariance over time. Strong positive correlations between ages 3 and 5 SDQ
scores were not significantly different from correlations between age 5 and 7
scores. Conduct problems and hyperactivity subscales independently predicted
developmental and clinical outcomes 2 years later. CONCLUSIONS: Satisfactory
psychometric properties of the adapted preschool version affirm its utility as a
screening tool to identify 3- to 4-year-olds with emotional and behavioral
difficulties.
PMID- 25847805
TI - Predicting neonatal intubation competency in trainees.
AB - BACKGROUND AND OBJECTIVES: Pediatric residency training programs are graduating
residents who are not competent in neonatal intubation, a vital skill needed for
any pediatrician involved in delivery room resuscitations. However, a precise
definition of competency during training is lacking. The objective of this study
was to more precisely define the trajectory toward competency in neonatal
intubation for pediatric residents, as a framework for later evaluating
complementary training tools. METHODS: This is a retrospective single-center
observational study of resident-performed neonatal intubations at Duke University
Medical Center between 2005 and 2013. Using a Bayesian statistical model,
intubation competency was defined when the resident attained a 75% likelihood of
intubating their next patient successfully. RESULTS: A total of 477 unique
intubation attempts by 105 residents were analyzed. The path to proficiency was
defined by a categorical or milestone learning event after which all learners
move toward competency in a similar manner. In our cohort, 4 cumulative successes
were needed to achieve competency. Only 24 of 105 (23%) achieved competency
during the study period. Residents who failed their first 2 opportunities,
compared with those successful on their first 2 opportunities, needed nearly
double the intubation exposure to achieve competency. CONCLUSIONS: Bayesian
statistics may be useful to more precisely describe neonatal intubation
competency in residents. Achieving competency in neonatal intubation appears to
be a categorical or milestone learning event whose timing varies between
residents. The current educational environment does not provide adequate
procedural exposure to achieve competency for most residents.
PMID- 25847806
TI - Linear growth and child development in low- and middle-income countries: a meta
analysis.
AB - BACKGROUND AND OBJECTIVE: The initial years of life are critical for physical
growth and broader cognitive, motor, and socioemotional development, but the
magnitude of the link between these processes remains unclear. Our objective was
to produce quantitative estimates of the cross-sectional and prospective
association of height-for-age z score (HAZ) with child development. METHODS:
Observational studies conducted in low- and middle-income countries (LMICs)
presenting data on the relationship of linear growth with any measure of child
development among children <12 years of age were identified from a systematic
search of PubMed, Embase, and PsycINFO. Two reviewers then extracted these data
by using a standardized form. RESULTS: A total of 68 published studies conducted
in 29 LMICs were included in the final database. The pooled adjusted standardized
mean difference in cross-sectional cognitive ability per unit increase in HAZ for
children <= 2 years old was +0.24 (95% confidence interval [CI], 0.14-0.33; I(2)
= 53%) and +0.09 for children > 2 years old (95% CI, 0.05-0.12; I(2) = 78%).
Prospectively, each unit increase in HAZ for children <= 2 years old was
associated with a +0.22-SD increase in cognition at 5 to 11 years after
multivariate adjustment (95% CI, 0.17-0.27; I(2) = 0%). HAZ was also
significantly associated with earlier walking age and better motor scores (P <
.05). CONCLUSIONS: Observational evidence suggests a robust positive association
between linear growth during the first 2 years of life with cognitive and motor
development. Effective interventions that reduce linear growth restriction may
improve developmental outcomes; however, integration with environmental,
educational, and stimulation interventions may produce larger positive effects.
PMID- 25847807
TI - Safely doing less and the new AAP bronchiolitis guideline.
PMID- 25847809
TI - The development or exacerbation of eating disorder symptoms after topiramate
initiation.
AB - The Food and Drug Administration recently approved topiramate for migraine
prevention in adolescents. Given the well-established appetite-suppressant side
effects of topiramate, as well as data suggesting a potential comorbidity between
migraine and eating disorders, susceptible young migraine patients may be at a
greater risk for the development or worsening of eating disorder symptoms with
topiramate therapy. This case series comprises 7 adolescent patients in whom
serious eating disorders developed or were exacerbated after the initiation of
topiramate therapy. Clinical characteristics of these patients are highlighted.
In addition, this case series provides guidelines for providers to use in
assessing eating disorders before prescribing topiramate for migraine prevention
in adolescents.
PMID- 25847808
TI - Firearm violence among high-risk emergency department youth after an assault
injury.
AB - BACKGROUND: The risk for firearm violence among high-risk youth after treatment
for an assault is unknown. METHODS: In this 2-year prospective cohort study, data
were analyzed from a consecutive sample of 14- to 24-year-olds with drug use in
the past 6 months seeking assault-injury care (AIG) at an urban level 1 emergency
department (ED) compared with a proportionally sampled comparison group (CG) of
drug-using nonassaulted youth. Validated measures were administered at baseline
and follow-up (6, 12, 18, 24 months). RESULTS: A total of 349 AIG and 250 CG
youth were followed for 24 months. During the follow-up period, 59% of the AIG
reported firearm violence, a 40% higher risk than was observed among the CG
(59.0% vs. 42.5%; relative risk [RR] = 1.39). Among those reporting firearm
violence, 31.7% reported aggression, and 96.4% reported victimization, including
19 firearm injuries requiring medical care and 2 homicides. The majority with
firearm violence (63.5%) reported at least 1 event within the first 6 months.
Poisson regression identified baseline predictors of firearm violence, including
male gender (RR = 1.51), African American race (RR = 1.26), assault-injury (RR =
1.35), firearm possession (RR = 1.23), attitudes favoring retaliation (RR =
1.03), posttraumatic stress disorder (RR = 1.39), and a drug use disorder (RR =
1.22). CONCLUSIONS: High-risk youth presenting to urban EDs for assault have
elevated rates of subsequent firearm violence. Interventions at an index visit
addressing substance use, mental health needs, retaliatory attitudes, and firearm
possession may help decrease firearm violence among urban youth.
PMID- 25847811
TI - How can follow-up of patients with Raynaud phenomenon be optimized?
AB - BACKGROUND Raynaud phenomenon (RP) is common worldwide and presents diagnostic
and therapeutic difficulties. We aimed to share our experience with optimizing of
patient follow-up by using the cold-stimulation test (CST). MATERIAL AND METHODS
Data of 81 patients admitted with RP symptomatology were collected. Demographic
data and symptoms were recorded. A scale was used for determining the severity of
disease at pre-treatment and post-treatment. CST was performed to all patients at
pre-treatment and post-treatment for assessment of treatment efficiency in follow
up. Results were analyzed with the SPSS for Mac 20.0 program. RESULTS All the
patients were male. Mean age was 22.3 +/- 2.14 (19-29). Mean duration of symptoms
from onset to present was 4.59 +/- 2.85 years. There were statistically
significant differences between pre-treatment and post-treatment hand
temperatures measured by CST (p<0.001). However, there were no statistically
significant differences between pre-treatment and post-treatment severity scores
of patients (p=0.135). CONCLUSIONS To quantitatively determine the treatment
efficacy, CST may be used instead of asking simple questions of patients.
PMID- 25847810
TI - Dynamics of Vibrio cholerae abundance in Austrian saline lakes, assessed with
quantitative solid-phase cytometry.
AB - In order to elucidate the main predictors of Vibrio cholerae dynamics and to
estimate the risk of Vibrio cholera-related diseases, a recently developed direct
detection approach based on fluorescence in situ hybridization and solid-phase
cytometry (CARD-FISH/SPC) was applied in comparison to cultivation for water
samples from the lake Neusiedler See, Austria and three shallow alkaline lakes
over a period of 20 months. Vibrio cholerae attached to crustacean zooplankton
was quantified via FISH and epifluorescence microscopy. Concentrations obtained
by CARD-FISH/SPC were significantly higher than those obtained by culture in
2011, but were mostly of similar magnitude in 2012. Maximum cell numbers were
1.26 * 10(6) V. cholerae per L in Neusiedler See and 7.59 * 10(7) V. cholerae per
L in the shallow alkaline lakes. Only on a few occasions during summer was the
crustacean zooplankton the preferred habitat for V. cholerae. In winter, V.
cholerae was not culturable but could be quantified at all sites with CARD
FISH/SPC. Beside temperature, suspended solids, zooplankton and ammonium were the
main predictors of V. cholerae abundance in Neusiedler See, while in the shallow
alkaline lakes it was organic carbon, conductivity and phosphorus. Based on the
obtained concentrations a first estimation of the health risk for visitors of the
lake could be performed.
PMID- 25847812
TI - Effect of initial GnRH and duration of progesterone insert treatment on the
fertility of lactating dairy cows.
AB - The study compared response to prostaglandin F2alpha (PG), synchrony of ovulation
and pregnancy per AI (P/AI) in a 5- vs a 7-day Ovsynch + PRID protocol and
investigated whether the initial GnRH affects P/AI in lactating dairy cows. Two
hundred and seventy-six cows (500 inseminations) were assigned to one of four
timed-AI (TAI) protocols: (i) PRID-7G; 100 MUg GnRH im, and a progesterone
releasing intravaginal device (PRID) for 7 days. At PRID removal, PG (500 MUg of
cloprostenol) was given im. Cows received the second GnRH treatment at 60 h after
PRID removal and TAI 12 h later. (ii) PRID-5G; as PRID-7G except the duration of
PRID, treatment was 5 days and PG was given twice (12 h apart). (iii) PRID-7NoG;
as PRID-7G except the initial GnRH, treatment was omitted. (iv) PRID-5NoG; as
PRID-7NoG except the duration of PRID, treatment was 5 days. Response to
treatments and pregnancy status at 32 and 60 days after TAI was determined by
ultrasonography. The percentage of cows ovulating before TAI was greatest in PRID
7G (17.1%), and the percentage of cows that did not have luteal regression was
greatest in PRID-5G (9.5%). The overall P/AI at 32 and 60 days did not differ
among TAI protocols. However, during resynchronization, cows subjected to the 5
day protocols had greater (p < 0.05) P/AI (45.3% vs 33.6%) than cows subjected to
the 7-day protocols. Pregnancy loss between 32 and 60 days tended (p = 0.10) to
be greater in cows that did not receive initial GnRH (14.8%) compared to those
that received GnRH (8.2%). In conclusion, the PRID-5G protocol resulted in fewer
cows responding to PG, but P/AI did not differ among TAI protocols. A 5-day
protocol resulted in more P/AI in resynchronized cows, and cows that did not
receive initial GnRH tended to experience more pregnancy losses.
PMID- 25847813
TI - Economic level and human longevity: Spatial and temporal variations and
correlation analysis of per capita GDP and longevity indicators in China.
AB - OBJECTIVE: We show the variation of longevity indicators in China during the past
60 years and its correlation patterns with per capita GDP (GDPpc) both at
provincial and inner-provincial level. METHODS: Population data from six national
population censuses in China (1953-2010) at provincial level and in several
typical provinces in 2010 at county-level were selected. Four main longevity
indicators were calculated. Pearson's r and distributed lags time series analysis
between longevity indicators and GDPpc were conducted. RESULTS: The results show
that Guangxi and Hainan Provinces maintain relatively high long-lived population
(population over the age of 90) across various population censuses. The
distributions of the population over the age of 80 and life expectancy are
significantly affected by both contemporaneous and historical GDPpc at provincial
level. However, areas of high long-lived population (over the age of 90) exhibit
continuously stable features that lack any significant correlation with GDPpc
both at provincial and inner-provincial level. CONCLUSION: Our results indicate a
mixed distribution pattern of several longevity indexes and different relation to
GDPpc. It shows consistent trend with Preston curve, that is, economic conditions
may have limited influence on human longevity, especially for those who live
longer than 90 years old. This study suggests that the economic development may
favor the local residents to have access to live as old as 80 years old, but it
is still difficult for most residents to reach the level of centenarians.
PMID- 25847814
TI - One-Pot Synthesis of 5-Amino-2,5-dihydro-1-benzoxepines: Access to
Pharmacologically Active Heterocyclic Scaffolds.
AB - A one-pot multibond-forming process involving a thermally mediated Overman
rearrangement and a ring closing metathesis reaction of allylic
trichloroacetimidates bearing a 2-allyloxyaryl group has been developed for the
synthesis of 5-amino-substituted 2,5-dihydro-1-benzoxepines. Chemoselective
reduction and functionalization of these compounds allowed access to a range of
pharmacologically active 5-amino-2,3,4,5-tetrahydro-1-benzoxepine scaffolds.
PMID- 25847816
TI - Scandium-catalyzed asymmetric 1,6-addition of 3-substituted oxindoles to linear
dienyl ketones.
AB - The first example of a N,N'-dioxide-Sc(III) -catalyzed 1,6-addition of 3
substituted oxindoles to dienyl ketones has been developed. This procedure
tolerates a relatively wide range of 3-substituted oxindoles under mild
conditions, facilitating the preparation of various chiral oxindoles with
quaternary stereocenters. In addition, the reliable catalyst was found to be
effective in the asymmetric 1,6-addition of both delta-unsubstituted and delta
methyl-substituted dienyl ketones, achieving excellent regioselectivities and
enantioselectivities (up to>99 % ee).
PMID- 25847815
TI - What is the function of mitochondrial networks? A theoretical assessment of
hypotheses and proposal for future research.
AB - Mitochondria can change their shape from discrete isolated organelles to a large
continuous reticulum. The cellular advantages underlying these fused networks are
still incompletely understood. In this paper, we describe and compare hypotheses
regarding the function of mitochondrial networks. We use mathematical and
physical tools both to investigate existing hypotheses and to generate new ones,
and we suggest experimental and modelling strategies. Among the novel insights we
underline from this work are the possibilities that (i) selective mitophagy is
not required for quality control because selective fusion is sufficient; (ii)
increased connectivity may have non-linear effects on the diffusion rate of
proteins; and (iii) fused networks can act to dampen biochemical fluctuations. We
hope to convey to the reader that quantitative approaches can drive advances in
the understanding of the physiological advantage of these morphological changes.
PMID- 25847817
TI - Changes in nutrient composition and in vitro ruminal fermentation of total mixed
ration silage stored at different temperatures and periods.
AB - BACKGROUND: Total mixed ration (TMR) is widely used for dairy cattle and needs to
be prepared daily because it deteriorates rapidly. Ensiling TMR allows
preservation and saves labour at the farm; however, silage fermentation may
influence various nutritional components. The objectives of this study were to
evaluate nutritional changes and in vitro rumen fermentation of TMR silage that
was stored at different temperatures and durations on a laboratory scale in
comparison with those of typical TMR before ensiling. RESULTS: No distinct
changes in crude protein (CP), neutral detergent fibre and non-fibrous
carbohydrate contents were observed during silage fermentation. However, clear
changes were observed in the soluble CP and soluble sugar fractions;
solubilisation of the CP fraction in TMR silage was enhanced by prolonged storage
and higher storage temperatures, and most soluble sugars were lost during
ensiling. Short-chain fatty acid concentrations in the in vitro rumen from TMRs
before and after ensiling were not significantly different; however, throughout
incubation, NH3 -N concentrations from TMR silages were significantly higher than
those from TMR before ensiling. CONCLUSION: A higher ruminal NH3 -N concentration
from TMR silage may be a result of a shortage of fermentable sugars and enhanced
deamination of CP. Feeding TMR ensiled under a high temperature must be
investigated to balance proteins and carbohydrates for rumen fermentation.
PMID- 25847818
TI - The use of ketamine as an antidepressant: a systematic review and meta-analysis.
AB - OBJECTIVE: The current meta-analysis examines the effects of ketamine infusion on
depressive symptoms over time in major depressive disorder (MDD) and bipolar
disorder (BD). METHODS: Following a systematic review of the literature, data
were extracted from 21 studies (n = 437 receiving ketamine) and analysed at four
post-infusion time points (4 h, 24 h, 7 days and 12-14 days). The moderating
effects of several factors were assessed including: repeat/single infusion,
diagnosis, open-label/participant-blind infusion, pre-post/placebo-controlled
design and the sex of patients. RESULTS: Effect sizes were significantly larger
for repeat than single infusion at 4 h, 24 h and 7 days. For single infusion
studies, effect sizes were large and significant at 4 h, 24 h and 7 days. The
percentage of males was a predictor of antidepressant response at 7 days. Effect
sizes for open-label and participant-blind infusions were not significantly
different at any time point. CONCLUSIONS: Single ketamine infusions elicit a
significant antidepressant effect from 4 h to 7 days; the small number of studies
at 12-14 days post infusion failed to reach significance. Results suggest a
discrepancy in peak response time depending upon primary diagnosis - 24 h for MDD
and 7 days for BD. The majority of published studies have used pre-post
comparison; further placebo-controlled studies would help to clarify the effect
of ketamine over time.
PMID- 25847820
TI - Biomolecular bases of the senescence process and cancer. A new approach to
oncological treatment linked to ageing.
AB - Human ageing is associated with a gradual decline in the physiological functions
of the body at multiple levels and it is a key risk factor for many diseases,
including cancer. Ageing process is intimately related to widespread cellular
senescence, characterised by an irreversible loss of proliferative capacity and
altered functioning associated with telomere attrition, accumulation of DNA
damage and compromised mitochondrial and metabolic function. Tumour and senescent
cells may be generated in response to the same stimuli, where either cellular
senescence or transformation would constitute two opposite outcomes of the same
degenerative process. This paper aims to review the state of knowledge on the
biomolecular relationship between cellular senescence, ageing and cancer.
Importantly, many of the cell signalling pathways that are found to be altered
during both cellular senescence and tumourigenesis are regulated through shared
epigenetic mechanisms and, therefore, they are potentially reversible. MicroRNAs
are emerging as pivotal players linking ageing and cancer. These small RNA
molecules have generated great interest from the point of view of future clinical
therapy for cancer because successful experimental results have been obtained in
animal models. Micro-RNA therapies for cancer are already being tested in
clinical phase trials. These findings have potential importance in cancer
treatment in aged people although further research-based knowledge is needed to
convert them into an effective molecular therapies for cancer linked to ageing.
PMID- 25847821
TI - A case of empyema and a posterior mediastinal abscess after an iliopsoas abscess
secondary to Crohn's disease.
PMID- 25847819
TI - Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy
versus intensity-modulated radiation therapy on the high-dose arm of the
Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.
AB - BACKGROUND: The authors analyzed a preliminary report of patient-reported
outcomes (PROs) among men who received high-dose radiation therapy (RT) on
Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial)
with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT).
METHODS: Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and
proximal seminal vesicles and were allowed an optional field reduction; then,
they received 23.4 Gy to the prostate only. Patients in the IMRT group received
79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0
months (baseline), 3 months, 6 months, 12 months, and 24 months and included
bladder and bowel function assessed with the Functional Alterations due to
Changes in Elimination (FACE) instrument and erectile function assessed with the
International Index of Erectile Function (IIEF). Analyses included the patients
who completed all data at baseline and for at least 1 follow-up assessment, and
the results were compared with an imputed data set. RESULTS: Of 763 patients who
were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded
to the FACE instrument and 505 patients and 577 patients who responded to the
IIEF were included in the completed and imputed analyses, respectively. There
were no significant differences between modalities for any of the FACE or IIEF
subscale scores or total scores at any time point for either the completed data
set or the imputed data set. CONCLUSIONS: Despite significant reductions in dose
and volume to normal structures using IMRT, this robust analysis of 3D-CRT and
IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual
functions for similar doses delivered to the prostate and proximal seminal
vesicles with IMRT compared with 3D-CRT delivered either to the prostate and
proximal seminal vesicles or to the prostate alone.
PMID- 25847822
TI - Sphincter-sparing intersphincteric rectal resection as an alternative to
proctectomy in long-standing fistulizing and stenotic Crohn's proctitis?
AB - PURPOSE: Long-standing fistulizing and stenotic proctitis (LFSP) in Crohn's
disease (CD) indicates the end stage of the disease. Definitive diversion such as
proctectomy is considered to be the only surgical option. The impact of
intersphincteric sphincter-sparing anterior rectal resection (IAR) as an
alternative to proctectomy is unclear. The aim of this study was to evaluate
feasibility, morbidity, outcome, and quality of life (QL) in patients with LFSP
undergoing intended IAR. PATIENTS AND METHODS: Out of a single institution
database, 15 patients with LFSP intended for surgery from 856 patients with CD
were selected for follow-up analyses. RESULTS: In 12/15 cases, IAR was carried
out while 3/15 patients underwent primary proctectomy due to malignancy (n = 2)
or due to patient's wish (n = 1). In one case, IAR revealed unexpected
malignancy, which led to secondary proctectomy. In patients with IAR, complete
healing of fistulas and stenosis was observed in 46% (n = 5) while 36% (n = 4) of
patients showed relapse of fistula and 18% (n = 2) developed restenosis.
Ileostomy closure was performed in seven patients from which six patients
remained stoma free. QL and fecal incontinence measured by standardized scoring
systems were unchanged while stool frequency was reduced after IAR in patients
with ileostomy closure. The rate of malignancy in this cohort was 20% (n = 3).
CONCLUSION: LFSP in CD was associated with 20% of malignant transformation.
Although IAR fails to improve QL, it is a suitable procedure for the treatment of
fistulas and stenosis associated with acceptable healing rates and can avoid a
permanent stoma.
PMID- 25847823
TI - Letter to the editor: mistaken inheritance.
PMID- 25847824
TI - Summary of the 2nd International Symposium on Arthrogryposis, St. Petersburg,
Russia, September 17-19, 2014.
AB - Enormous progress has been made in understanding the etiology and therapies for
arthrogryposis (multiple congenital contractures). A 2nd International Symposium
on Arthrogryposis was sponsored by the Turner Institute in St. Petersburg,
Russia. Olga Agranovich, Head of the Arthrogryposis Department of the Turner
Institute, organized this special meeting. Care providers from multiple
disciplines from all over the world representing 18 nations attended.
Participants included: Pediatric orthopedic specialists, rehabilitation
physicians, occupational therapists, physical therapists, medical geneticists,
neurologists, craniofacial physicians, psychologists, developmental biologists,
as well as representatives from parent support groups. The 1st symposium
established the need for a collaborative and interdisciplinary approach to the
treatment of arthrogryposis, engagement of parent support organizations, and the
aim for more research. The Second Symposium highlighted the continuing need for
more research on various therapies, identification of different types of
arthrogryposis, standardized descriptions of severity, development of new
orthotics, improved prenatal diagnosis, and studying adult outcome. Major
progress has been made on both upper and lower limb treatments.
PMID- 25847825
TI - Selection and evolutionary potential of spring arrival phenology in males and
females of a migratory songbird.
AB - The timing of annual life-history events affects survival and reproduction of all
organisms. A changing environment can perturb phenological adaptations and an
important question is if populations can evolve fast enough to track the
environmental changes. Yet, little is known about selection and evolutionary
potential of traits determining the timing of crucial annual events. Migratory
species, which travel between different climatic regions, are particularly
affected by global environmental changes. To increase our understanding of
evolutionary potential and selection of timing traits, we investigated the
quantitative genetics of arrival date at the breeding ground using a
multigenerational pedigree of a natural great reed warbler (Acrocephalus
arundinaceus) population. We found significant heritability of 16.4% for arrival
date and directional selection for earlier arrival in both sexes acting through
reproductive success, but not through lifespan. Mean arrival date advanced with 6
days over 20 years, which is in exact accordance with our predicted evolutionary
response based on the breeder's equation. However, this phenotypic change is
unlikely to be caused by microevolution, because selection seems mainly to act on
the nongenetic component of the trait. Furthermore, demographical changes could
also not account for the advancing arrival date. Instead, a strong correlation
between spring temperatures and population mean arrival date suggests that
phenotypic plasticity best explains the advancement of arrival date in our study
population. Our study dissects the evolutionary and environmental forces that
shape timing traits and thereby increases knowledge of how populations cope with
rapidly changing environments.
PMID- 25847826
TI - [Preterm rupture of membranes: Is home care a safe management?].
AB - OBJECTIVE: Compare the maternal and neonatal outcomes in pregnancies complicated
by preterm prelabour rupture of membranes (PPROM), which were managed either at
home (HAD) or hospital (HC). MATERIALS AND METHODS: Retrospective study in two
level III maternities during 2 years. Inclusion criteria in HAD were: singleton
pregnancy, PPROM between 24 and 35 weeks of gestation, absence of
chorioamnionitis, clinical stability at D7 of the rupture, cervical dilatation <3
cm, patient residing in the geographic area. RESULTS: Thirty-two patients were
included in the HAD group and 24 in the HC group. Our populations were similar in
the 2 groups. The duration of latency was longer in the HAD group than in the HC
group (27.5 d [20-37] versus 16.5 d [12.5 to 29.5]; P=0.026). Patients in the HAD
group received fewer antibiotics with a similar rate of chorioamnionitis. No
difference in terms of obstetrical and neonatal outcomes was observed. Number of
days in neonatal resuscitation was lower in the HAD group than in the HC group
(12.5 d [10-22] versus 43 d [20-52]; P=0.003). CONCLUSION: HAD seems to be an
alternative to continuous hospitalization for patients followed for PPROM between
24 and 35 weeks. A randomized study with a larger number of patients, including
other data such as maternal satisfaction and cost analysis, would be interesting
to confirm those preliminary results.
PMID- 25847835
TI - Distinct pathways for norepinephrine- and opioid-triggered antinociception from
the amygdala.
AB - BACKGROUND: The amygdala has an important role in pain and pain modulation. We
showed previously in animal studies that alpha2 -adrenoreceptor activation in the
central nucleus of the amygdala (CeA) mediates hypoalgesia produced by restraint
stress, and that direct application of an alpha2 -agonist in this region produces
analgesia. AIMS: In the present animal experiments, we investigated the pathways
through which alpha2 -sensitive systems in the CeA produce behavioural analgesia.
The CeA has dense connections to a descending pain modulatory network, centred in
the midbrain periaqueductal grey (PAG) and the rostral ventromedial medulla
(RVM), which is implicated in various forms of stress-related hypoalgesia and
which mediates the antinociceptive effect of morphine applied in the basolateral
amygdala. We investigated whether this circuit mediates the hypoalgesic effects
of alpha2 -adrenergic agonist administration into the CeA as well as the
contribution of endogenous opioids and cannabinoids. We also tested the
possibility that activation of alpha2 -receptors in the CeA produces
antinociception by recruitment of noradrenergic pathways projecting to the spinal
cord. RESULTS: Hypoalgesia resulting from bilateral application of the alpha2
adrenergic agonist clonidine in the CeA was not reversed by chemical inactivation
of the RVM or by systemic injections of naloxone (MU-opioid antagonist) or
rimonabant (CB1 antagonist). By contrast, spinal alpha2 -receptor blockade
(intrathecal idazoxan) completely prevented the hypoalgesic effect of clonidine
in the CeA, and unmasked a small but significant hyperalgesia. CONCLUSION: In
rats, adrenergic actions in the CeA mediating hypoalgesia require spinal
adrenergic neurotransmission but not the PAG-RVM pain modulatory network, or
opiate or cannabinoid systems.
PMID- 25847836
TI - Evidence of a target resistance to antivitamin K rodenticides in the roof rat
Rattus rattus: identification and characterisation of a novel Y25F mutation in
the Vkorc1 gene.
AB - BACKGROUND: In spite of intensive use of bromadiolone, rodent control was
inefficient on a farm infested by rats in Zaragoza, Spain. While metabolic
resistance was previously described in this rodent species, the observation of a
target resistance to antivitamin K rodenticides had been poorly documented in
Rattus rattus. RESULTS: From rats trapped on the farm, cytochrome b and Vkorc1
genes were amplified by PCR and sequenced in order to identify species and detect
potential Vkorc1 mutations. VKORC1-deduced amino acid sequences were thus
expressed in Pichia pastoris, and inhibition constants towards various
rodenticides were determined. The ten rats trapped on the farm were all
identified as R. rattus. They were found to be homozygous for the g.74A>T
nucleotide replacement in exon 1 of the Vkorc1 gene, leading to p.Y25F mutation.
This mutation led to increased apparent inhibition constants towards various
rodenticides, probably caused by a partial loss of helical structure of TM4.
CONCLUSION: The p.Y25F mutation detected in the Vkorc1 gene in R. rattus trapped
on the Spanish farm is associated with the resistance phenotype to bromadiolone
that has been observed. It is the first evidence of target resistance to
antivitamin K anticoagulants in R. rattus.
PMID- 25847837
TI - The Cardioprotective Effect of Icariin on Ischemia-Reperfusion Injury in Isolated
Rat Heart: Potential Involvement of the PI3K-Akt Signaling Pathway.
AB - AIMS: Icariin (ICA), a flavonoid isolated from epimedii, has been reported to
have potential protective effects on the cardiovascular system. This study is to
investigate the effect and the underlying mechanisms of ICA on
ischemia/reperfusion (I/R) injury. METHODS: Wister rat hearts were subjected to
I/R using Langendorff perfusion system. Cardiac function, myocardial infarct
size, lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) activities in
coronary effluent, and superoxide dismutase (SOD) and malondialdehyde (MDA)
content in heart tissue and cardiomyocyte apoptosis were assayed. RESULTS:
Compared with the I/R group, ICA treatment significantly improved cardiac
function, decreased myocardial infarct size, enzyme activity, oxidative stress,
and apoptosis. In addition, ICA treatment lead to an increased p-Akt level, which
was partially reversed by LY294002, a PI3K pathway inhibitor. CONCLUSION: Our
study suggests that ICA has a cardioprotective effect against I/R injury, which
is associated with its antioxidative and anti-apoptotic effect, at least
partially, through the activation of PI3K-Akt signaling pathway.
PMID- 25847838
TI - Fingerprinting profile of polysaccharides from Lycium barbarum using multiplex
approaches and chemometrics.
AB - Techniques including ultraviolet-visible spectra (UV), high performance size
exclusion chromatography (HPSEC), Fourier-transform infrared spectroscopy (FT-IR)
and pre-column derivatization high-performance liquid chromatography (PCD-HPLC)
were used in the fingerprinting analysis of Lycium barbarum polysaccharides
(LBPs) from different locations and varieties. Multiple fingerprinting profiles
were used to evaluate the similarity and classification of different LBPs with
the help of chemometrics. The results indicated that sixteen batches of LBPs had
good consistency, and fingerprinting techniques were simple and robust for
quality control of LBPs as well as related products. In addition, fingerprinting
techniques combined with chemometrics could also be used to identify different
cultivation locations of LBPs samples. Finally, four monosaccharides
(galacturonic acid, glucose, galactose and arabinose) and the absorptions of
stretching vibration of ester carbonyl groups as well as NH variable angle
vibration of -CONH- could be selected as herbal markers to distinguish different
samples.
PMID- 25847839
TI - Alginate-based hydrogels with improved adhesive properties for cell
encapsulation.
AB - Hydrogel-based biomaterials are ideal scaffolding matrices for
microencapsulation, but they need to be modified to resemble the mechanical,
structural and chemical properties of the native extracellular matrix. Here, we
compare the mechanical properties and the degradation behavior of unmodified and
modified alginate hydrogels in which cell adhesive functionality is conferred
either by blending or covalently cross-linking with gelatin. Furthermore, we
measure the spreading and proliferation of encapsulated osteoblast-like MG-63
cells. Alginate hydrogels covalently crosslinked with gelatin show the highest
degree of cell adhesion, spreading, migration, and proliferation, as well as a
faster degradation rate, and are therefore a particularly suitable material for
microencapsulation.
PMID- 25847840
TI - High-temporal velocity-encoded MRI for the assessment of left ventricular inflow
propagation velocity: Comparison with color M-mode echocardiography.
AB - PURPOSE: To develop an alternative method for Vp-assessment using high-temporal
velocity-encoded magnetic resonance imaging (VE-MRI). Left ventricular (LV)
inflow propagation velocity (Vp) is considered a useful parameter in the complex
assessment of LV diastolic function and is measured by Color M-mode
echocardiography. MATERIALS AND METHODS: A total of 43 patients diagnosed with
ischemic heart failure (61 +/- 11 years) and 22 healthy volunteers (29 +/- 13
years) underwent Color M-mode echocardiography and VE-MRI to assess the inflow
velocity through the mitral valve (mean interexamination time 14 days). Temporal
resolution of VE-MRI was 10.8-11.8 msec. Local LV inflow velocity was sampled
along a 4-cm line starting from the tip of the mitral leaflets and for
consecutive sample points the point-in-time was assessed when local velocity
exceeded 30 cm/s. From the position-time relation, Vp was calculated by both the
difference quotient (Vp-MRI-DQ) as well as from linear regression (Vp-MRI-LR).
RESULTS: Good correlation was found between Vp-echo and both Vp-MRI-DQ (r = 0.83,
P < 0.001) and Vp-MRI-LR (r = 0.84, P < 0.001). Vp-MRI showed a significant but
small underestimation as compared to Vp measured by echocardiography (Vp-MRI-DQ:
5.5 +/- 16.2 cm/s, P = 0.008; Vp-MRI-LR: 9.9 +/- 15.2 cm/s, P < 0.001). Applying
age-related cutoff values for Vp to identify LV impaired relaxation, kappa
agreement with echocardiography was 0.72 (P < 0.001) for Vp-MRI-DQ and 0.69 (P <
0.001) for Vp-MRI-LR. CONCLUSION: High temporal VE-MRI represents a novel
approach to assess Vp, showing good correlation with Color M-mode
echocardiography. In healthy subjects and patients with ischemic heart failure,
this new method demonstrated good agreement with echocardiography to identify LV
impaired relaxation.
PMID- 25847841
TI - Osteopontin expression in biopsies of calciphylaxis.
AB - BACKGROUND: Calciphylaxis combines features of vascular thrombotic occlusion and
endoluminal calcification. In this study we examine the expression of osteopontin
as a diagnostic marker and its role in lesional pathogenesis. METHODS: 25
formalin-fixed, paraffin embedded skin biopsies of 20 females and 5 males (mean
age of 60 years) with a diagnosis of calciphylaxis were assessed for osteopontin
expression. RESULTS: Lower extremities were the most commonly involved areas;
however a truncal and genital distribution was also noted in 3 cases. Renal
failure was present in 21 of 25 cases. One patient had myeloproliferative
disorder and one patient had advanced colon cancer. The dominant pathology was
localized to the subcutaneous fat, characterized by mural calcification and
luminal thrombosis affecting capillaries, venules, arterioles and small arteries.
In 2 cases, a subcutaneous thrombogenic vasculopathy without calcification was
noted. Osteopontin expression was confined to the subcutis, being most striking
in calcified vessels but also apparent in vessels without calcification,
including mineral poor variants of calciphylaxis. CONCLUSION: Calciphylaxis
represents a unique calcific thrombogenic vasculopathy, not limited to renal
failure. Ectopic osteopontin expression may define a critical and initial event
in the calciphylaxis pathogenesis. Therapeutic agents designed to reduce
osteopontin expression may be of value in its treatment.
PMID- 25847842
TI - The lithic industry of Sima del Elefante (Atapuerca, Burgos, Spain) in the
context of Early and Middle Pleistocene technology in Europe.
AB - This paper presents the lithic assemblages documented at Sima del Elefante (TE)
and their importance in the context of the Early and Middle Pleistocene human
occupation of Europe. We also study changes in human behaviour within the context
of the palaeoenvironmental evolution of the Sierra de Atapuerca. This site has
characteristics that are of great value for the study of human evolution. The
lower levels of TE (Units TE7-TE14) are an essential reference for understanding
the early stages of the colonization of Europe. The TE9c level has provided stone
tools (Mode 1), faunal remains, and human fossils dated to 1.22 Ma (millions of
years ago). Moreover, this is one of the few European sites with a stratigraphic
sequence that includes remains of human occupations predating the Jaramillo
subchron (Early Pleistocene) and from the Late Middle Pleistocene (Units TE18
TE19). Despite this, the presence of archaeologically sterile units (TE15-17)
prevents us from establishing a continuous relationship between the Early and
Middle Pleistocene human settlements and, consequently, between their
technological and behavioural differences. We can, however compare the
technological and palaeoeconomic strategies adopted by different species of
hominins during two key phases of the occupation of Europe.
PMID- 25847843
TI - Self-nanoemulsifying drug delivery system of trans-cinnamic acid: formulation
development and pharmacodynamic evaluation in alloxan-induced type 2 diabetic rat
model.
AB - The objective of this study was to formulate a self-nanoemulsifying oral drug
delivery system (SNEDDS) for the poorly water-soluble trans-Cinnamic acid (t-CA
SNEDDS) that could be evaluated for its antihyperglycemic efficacy in comparison
to the parent t-CA in an alloxan-induced diabetic rat model. A SNEDDS formulation
consisting of 60% surfactant (Kolliphor EL), 10% co-surfactant (PEG 400) and 30%
oil (isopropyl myristate) proved to be optimal. t-CA SNEDDS (80 mg/kg, p.o.), t
CA suspension (80 mg/kg, p.o.), and Metformin Hydrochloride Tablets (230 mg/kg,
p.o.) were administer qdfor 30 days to diabetic rats. After treatment the body
weight of diabetic rats was increased, blood glucose levels, total cholesterol,
and triglyceride in the serum tended to be normalized, while the levels of
alanine aminotransferase and aspartate aminotransferase were markedly decreased.
The effects of t-CA SNEDDS were superior to that of the t-CA suspension. The
present study demonstrated that t-CA was effective in attenuating the effects of
alloxan treatment and that t-CA SNEDDS with a more favorable absorption and
enhanced bioavailability is more effective than t-CA.
PMID- 25847844
TI - Surface Chirality of Gly-Pro Dipeptide Adsorbed on a Cu(110) Surface.
AB - The adsorption of chiral Gly-Pro dipeptide on Cu(110) has been characterized by
combining in situ polarization modulation infrared reflection absorption
spectroscopy (PM-RAIRS) and X-ray photoelectron spectroscopy (XPS). The chemical
state of the dipeptide, and its anchoring points and adsorption geometry, were
determined at various coverage values. Gly-Pro molecules are present on Cu(110)
in their anionic form (NH2 /COO(-)) and adsorb under a 3-point binding via both
oxygen atoms of the carboxylate group and via the nitrogen atom of the amine
group. Low-energy electron diffraction (LEED) and scanning tunneling microscopy
(STM) have shown the presence of an extended 2D chiral array, sustained via
intermolecular H-bonds interactions. Furthermore, due to the particular shape of
the molecule, only one homochiral domain is formed, creating thus a truly chiral
surface.
PMID- 25847845
TI - Susceptibility to male infertility: replication study in Japanese men looking for
an association with four GWAS-derived loci identified in European men.
AB - PURPOSE: A previous genome-wide association study in European men identified four
single nucleotide polymorphism (SNP) loci associated with male infertility. Our
aim was to replicate, if possible, the association of these SNPs with Japanese
male infertility. METHODS: We genotyped four SNPs (rs5911500, rs10246939,
rs2059807, and rs11204546) in 517 Japanese patients with male infertility and 369
fertile controls using SNP-specific real-time polymerase chain reaction TaqMan
assays. Subsequently, we divided patients with male infertility into azoospermia
(n = 417) and oligospermia subgroups (n = 70). RESULTS: The four SNPs previously
identified in European men showed no significant association with collective male
infertility in our Japanese cohort. However, allele frequency analysis did
indicate a significantly higher frequency of the rs11204546 C allele of the OR2W3
gene in the oligospermia subset of infertility patients compared with controls (p
= 0.0037; odds ratio = 1.74; 95 % confidence interval, 1.21-2.53). CONCLUSIONS:
Although this study was somewhat limited by overall sample size, the OR2W3 gene
polymorphism rs11204546 was significantly associated with oligospermia in
Japanese men, suggesting that OR2W3 might be involved in genetic susceptibility
to Japanese male infertility as well as in European males.
PMID- 25847846
TI - Evaluation of a SiPM array coupled to a Gd3Al2Ga3O12:Ce (GAGG:Ce) discrete
scintillator.
AB - PURPOSE: In this study, we present the results of the evaluation of the SensL
ArraySL-4 photo-detector, coupled to a 6 * 6 GAGG:Ce scintillator array, with 2 *
2 * 5 mm(3) crystal size elements for possible applications in medical imaging
detectors with focus in PET applications. Experimental evaluation was carried out
with (22)Na and (137)Cs radioactive sources and the parameters studied were
energy resolution and peak to valley ratio. METHODS: ArraySL-4 is a commercially
available, 4 * 4 array detector covering an active area of 13.4 mm(2). The
GAGG:Ce scintillator array used in this study has 0.1 mm thickness BaSO4
reflector material between the crystal elements. A symmetric resistive voltage
division matrix was applied, which reduces the 16 outputs of the array to 4
position signals. A Field Programmable Gate Array was used for triggering and
digital processing of the signal pulses acquired using free running Analog to
Digital Converters. RESULTS: Raw images and horizontal profiles of the 6 * 6
GAGG:Ce scintillator array produced under 511 keV and 662 keV excitation are
illustrated. Moreover, the energy spectra obtained with (22)Na and (137)Cs
radioactive sources from a single 2 * 2 * 5 mm(3) GAGG:Ce scintillator are shown.
The peak to valley ratio and the mean energy resolution values are reported.
CONCLUSIONS: The acquired raw image of the GAGG:Ce crystal array under 511 keV
excitation shows a clear visualization of all discrete scintillator elements with
a mean peak to valley ratio equal to 40. The mean energy resolution was measured
equal to 10.5% and 9% respectively under 511 keV and 662 keV irradiation.
PMID- 25847847
TI - Causal discovery in an adult ADHD data set suggests indirect link between DAT1
genetic variants and striatal brain activation during reward processing.
AB - Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable
disorder affecting both children and adults. One of the candidate genes for ADHD
is DAT1, encoding the dopamine transporter. In an attempt to clarify its mode of
action, we assessed brain activity during the reward anticipation phase of the
Monetary Incentive Delay (MID) task in a functional MRI paradigm in 87 adult
participants with ADHD and 77 controls (average age 36.5 years). The MID task
activates the ventral striatum, where DAT1 is most highly expressed. A previous
analysis based on standard statistical techniques did not show any significant
dependencies between a variant in the DAT1 gene and brain activation [Hoogman et
al. (2013); Neuropsychopharm 23:469-478]. Here, we used an alternative method for
analyzing the data, that is, causal modeling. The Bayesian Constraint-based
Causal Discovery (BCCD) algorithm [Claassen and Heskes (2012); Proceedings of the
28th Conference on Uncertainty in Artificial Intelligence] is able to find direct
and indirect dependencies between variables, determines the strength of the
dependencies, and provides a graphical visualization to interpret the results.
Through BCCD one gets an opportunity to consider several variables together and
to infer causal relations between them. Application of the BCCD algorithm
confirmed that there is no evidence of a direct link between DAT1 genetic
variability and brain activation, but suggested an indirect link mediated through
inattention symptoms and diagnostic status of ADHD. Our finding of an indirect
link of DAT1 with striatal activity during reward anticipation might explain
existing discrepancies in the current literature. Further experiments should
confirm this hypothesis. (c) 2015 Wiley Periodicals, Inc.
PMID- 25847849
TI - Improvements in Physicians' Knowledge, Difficulties, and Self-Reported Practice
After a Regional Palliative Care Program.
AB - CONTEXT: Although several studies have explored the effects of regional
palliative care programs, no studies have investigated the changes in physician
related outcomes. OBJECTIVES: The primary aims of this study were to: (1) clarify
the changes in knowledge, difficulties, and self-reported practice of physicians
before and after the intervention, (2) explore the potential associations between
the level of physicians' participation in the program and outcomes, and (3)
identify the reasons and characteristics of physicians who did not participate in
the program. METHODS: As a part of the regional palliative care intervention
trial, questionnaires were sent to physicians recruited consecutively to obtain a
representative sample of each region. Physician-reported knowledge, difficulty of
palliative care, and self-perceived practice were measured using the Palliative
Care Knowledge Test, Palliative Care Difficulty Scale, and Palliative Care Self
Reported Practice Scale (PCPS), respectively. The level of their involvement in
the program and reason for non-participation were ascertained from self-reported
questionnaires. RESULTS: The number of eligible physicians identified was 1870 in
pre-intervention and 1763 in post-intervention surveys, and we obtained 911 and
706 responses. Total scores of the Palliative Care Knowledge Test, PCPS, and PCPS
were significantly improved after the intervention, with effect sizes of 0.30,
0.52, and 0.17, respectively. Physicians who participated in workshops more
frequently were significantly more likely to have better knowledge, less
difficulties, and better self-reported practice. CONCLUSION: After the regional
palliative care program, there were marked improvements in physicians' knowledge
and difficulties. These improvements were associated with the level of
physicians' participation in the program.
PMID- 25847848
TI - The Accuracy of Physicians' Clinical Predictions of Survival in Patients With
Advanced Cancer.
AB - CONTEXT: Accurate prognoses are needed for patients with advanced cancer.
OBJECTIVES: To evaluate the accuracy of physicians' clinical predictions of
survival (CPS) and assess the relationship between CPS and actual survival (AS)
in patients with advanced cancer in palliative care units, hospital palliative
care teams, and home palliative care services, as well as those receiving
chemotherapy. METHODS: This was a multicenter prospective cohort study conducted
in 58 palliative care service centers in Japan. The palliative care physicians
evaluated patients on the first day of admission and followed up all patients to
their death or six months after enrollment. We evaluated the accuracy of CPS and
assessed the relationship between CPS and AS in the four groups. RESULTS: We
obtained a total of 2036 patients: 470, 764, 404, and 398 in hospital palliative
care teams, palliative care units, home palliative care services, and
chemotherapy, respectively. The proportion of accurate CPS (0.67-1.33 times AS)
was 35% (95% CI 33-37%) in the total sample and ranged from 32% to 39% in each
setting. While the proportion of patients living longer than CPS (pessimistic
CPS) was 20% (95% CI 18-22%) in the total sample, ranging from 15% to 23% in each
setting, the proportion of patients living shorter than CPS (optimistic CPS) was
45% (95% CI 43-47%) in the total sample, ranging from 43% to 49% in each setting.
CONCLUSION: Physicians tend to overestimate when predicting survival in all
palliative care patients, including those receiving chemotherapy.
PMID- 25847850
TI - Stercoral Perforation of the Colon: A Potentially Fatal Complication of Opioid
Induced Constipation.
AB - Stercoral perforation of the colon is a rare complication of constipation, and
there have only been a few reported cases of stercoral perforation of the colon
secondary to opioid-induced constipation. This article describes such a case in a
cancer survivor with chronic cancer-related pain and reviews the medical/surgical
literature on stercoral perforation of the colon.
PMID- 25847851
TI - Cost Savings Associated With an Inpatient Palliative Care Unit: Results From the
First Two Years.
AB - CONTEXT: Palliative care consultation services (PCCS) decrease costs for patients
by matching treatments received to patients' and families' goals of care.
However, few studies have examined the costs of a specialized palliative care
unit (PCU). OBJECTIVES: To quantitatively describe Mount Sinai Hospital's PCU's
first two years of operation; to examine how patient-related costs changed in the
days before and after transfer to PCU; and to compare cost savings of PCU to
those of PCCS. METHODS: Cost and administrative data from PCU patients from the
first 24.5 months of our PCU's operation were analyzed. To compare costs between
PCU and PCCS patients, we matched PCU patients to similar PCCS patients and used
propensity scores to adjust for differences across groups. RESULTS: The PCU
admitted 1107 patients in its first 24.5 months. Over this time frame, there was
a statistically significant (P < 0.001) decrease in average daily direct costs
per patient. The mean of patients' average cost per day was $687 less while on
the PCU than before transfer to PCU. Among patients who died in the hospital,
average daily direct cost per patient in the days after transfer to PCU was $240
lower as compared with patients being followed by PCCS on the general hospital
wards (SE = $45, P < 0.001). CONCLUSION: Among patients who died in the hospital,
transfer to a PCU is associated with significant cost savings as compared with
patients on hospital wards who are seen by a PCCS.
PMID- 25847852
TI - Physical and Psychological Distress Are Related to Dying Peacefully in Residents
With Dementia in Long-Term Care Facilities.
AB - CONTEXT: Although dying peacefully is considered an important outcome of high
quality palliative care, large-scale quantitative research on dying peacefully
and the factors associated with a peaceful death is lacking. OBJECTIVES: To gain
insight into how many residents with dementia in long-term care facilities die
peacefully, according to their relatives, and whether that assessment is
correlated with observed physical and psychological distress. METHODS: This was a
retrospective cross-sectional study of deceased nursing home residents in a
representative sample of long-term care facilities in Flanders, Belgium (2010).
Structured post-mortem questionnaires were completed by relatives of the
resident, who were asked to what extent they agreed that the resident "appeared
to be at peace" during the dying process. Spearman correlation coefficients gave
the correlations between physical and psychological distress (as measured using
the Symptom Management at the End of Life with Dementia and Comfort Assessment in
Dying at the End of Life with Dementia scales) and dying peacefully (as measured
using the Quality of Dying in Long Term Care instrument). RESULTS: The sample
comprised 92 relatives of deceased residents with dementia. In 54% of cases,
relatives indicated that the resident died peacefully. Weak-to-moderate
correlations (0.2-0.57) were found between dying peacefully and physical distress
in the last week of life. Regarding psychological distress, weak-to-moderate
correlations were found for both the last week (0.33-0.44) and last month of life
(0.28-0.47). CONCLUSION: Only half of the residents with dementia died peacefully
as perceived by their relatives. Relatives' assessment of whether death was
peaceful is related to both physical and psychological distress. Further
qualitative research is recommended to gain more in-depth insights into the
aspects on which relatives base their judgment of dying peacefully.
PMID- 25847854
TI - Evaluation of competence-based teaching in higher education: From theory to
practice.
AB - Competence-based teaching in higher education institutions and its evaluation
have become a prevalent topic especially in the European Union. However,
evaluation instruments are often limited, for example to single student
competencies or specific elements of the teaching process. The present paper
provides a more comprehensive evaluation concept that contributes to sustainable
improvement of competence-based teaching in higher education institutions. The
evaluation concept considers competence research developments as well as the
participatory evaluation approach. The evaluation concept consists of three
stages. The first stage evaluates whether the competencies students are supposed
to acquire within the curriculum (ideal situation) are well defined. The second
stage evaluates the teaching process and the competencies students have actually
acquired (real situation). The third stage evaluates concrete aspects of the
teaching process. Additionally, an implementation strategy is introduced to
support the transfer from the theoretical evaluation concept to practice. The
evaluation concept and its implementation strategy are designed for internal
evaluations in higher education and primarily address higher education
institutions that have already developed and conducted a competence-based
curriculum.
PMID- 25847853
TI - Microsurgical ear replantation-is venous repair necessary?-A systematic review.
AB - BACKGROUND: A common postoperative observation after microsurgical ear
replantation has been venous congestion necessitating alternate modes of
decongestion, frequently in conjunction with blood transfusion. A comprehensive
literature search was performed to assess the relationship between mode of
vascular reconstruction and postoperative outcome as well as postoperative
transfusion requirement after microsurgical ear replantation. METHODS: The search
was limited to cases of microsurgical ear replantation following complete
amputation. Only articles published in English and indexed in PubMed were
included. RESULTS: The initial search retrieved 285 articles, which was narrowed
down to 40 articles reporting on 60 cases that matched the aforementioned
criteria. Reconstruction of the arterial and venous limb (Group 1) was performed
in 63.3% of patients and artery-only anastomosis (Group 2) was performed in
31.7%. Among measurable outcomes, only the duration of surgery was significantly
different between groups (2.6 hours longer in Group 1 than Group 2; P = 0.0042).
CONCLUSION: In light of contemporary data demonstrating successful artery-only
ear replantation, replantation should not be abandoned when unable to establish
venous outflow microsurgically. (c) 2015 Wiley Periodicals, Inc. Microsurgery
36:345-350, 2016.
PMID- 25847855
TI - Factors Affecting Indigenous West Australians' Health Behavior: Indigenous
Perspectives.
AB - The factors driving the disparity in health outcomes between Indigenous and non
Indigenous Australians include socio-economic factors, racism, and history. The
current study focused on exploring Indigenous participants' perspectives of the
factors that affect the health behavior of their community members. Participatory
action research methodology and a grounded theory approach were utilized. In
total, 120 members of two urban West Australian Indigenous communities
participated in focus group discussions. There was substantial similarity between
the themes that emerged within the discussions held in the two communities.
Factors relating to culture, social connections, racism, communication, and
personal aspects were particularly salient to health behavior of the
participants. Several of the themes including culture, racism, communication, and
distrust highlight the tension caused by being a member of a minority cultural
group that has been marginalized by the practices and attitudes of the dominant
cultural group. Personal choice was sometimes prioritized over health.
PMID- 25847856
TI - Exploring the Hidden Barriers in Knowledge Translation: A Case Study Within an
Academic Community.
AB - Debates about knowledge translation (KT) typically focus on the research-practice
gap, which appears to be premised on the assumption that academics are a
homogeneous collective, sharing a common view. We argue that a number of hidden
barriers need to be addressed related to the understanding, interpretation,
ability, and commitment to translate knowledge within academic communities. We
explore this by presenting a qualitative case study in a health sciences faculty.
Applying organizational and management theory, we discuss different types of
boundaries and the resultant barriers generated, ranging from diversity in
understanding and perceptions of KT to varying motivations and incentives to
engage in translational activity. We illustrate how we are using the empirical
findings to inform the development of a KT strategy that targets the identified
barriers. Investing in this internal KT-focused activity is an important step to
maximize the potential of future collaborations between producers and users of
research in health care.
PMID- 25847857
TI - Novel therapeutic approach for neurogenic erectile dysfunction: effect of
neurotrophic tyrosine kinase receptor type 1 monoclonal antibody.
AB - BACKGROUND: Erectile dysfunction (ED) is a major health issue in aged
populations, and neurogenic ED is particularly difficult to treat. Novel
therapeutic approaches are needed for treatment of neurogenic ED of peripheral
origin. OBJECTIVE: To investigate the therapeutic effects of a neurotrophic
tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) on erectile
function and sexual behavior in a rat model of cavernous nerve injury (CNI).
DESIGN, SETTING, AND PARTICIPANTS: In one experiment, 84 male rats were randomly
assigned to seven groups. The groups underwent either CNI or sham surgery,
subsequent injection into the major pelvic ganglion (IMPG) of phosphate-buffered
saline (PBS), an immunoglobulin G (IgG) control, or TrkA-mAb, and then
intracavernosal (IC) injection of either PBS or varying TrkA-mAb concentrations
immediately after surgery and then 1 wk later. Erectile function was assessed and
histologic/molecular analyses were performed at 6 wk after surgery. In a second
experiment, 36 male rats were randomly divided into three groups. The groups
underwent CNI or sham surgery and then IC injection of PBS, IgG, or TrkA-mAb
immediately after surgery and for 5 wk thereafter. At 6 wk after surgery, the
performance of the rats in sexual behavior tests was videotaped. INTERVENTION:
CNI or sham surgery; IMPG of PBS, IgG, or TrkA-mAb; IC injection of PBS or TrkA
mAb. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The intracavernous pressure
response to cavernous nerve electrostimulation was measured and midpenile cross
sections were histologically examined. Western blotting (WB) of cavernous tissue
protein was performed. Rats were assessed for chasing, mounting, intromission,
and ejaculation behaviors during sexual behavior tests. The data were analyzed
using one-way analysis of variance followed by the Tukey-Kramer t test. RESULTS
AND LIMITATIONS: Recovery of erectile function of varying degrees was observed in
the TrkA-mAb groups. TrkA-mAb treatment significantly suppressed tyrosine
hydroxylase-positive nerve fibers in the corpus cavernosum and enhanced neuronal
nitric oxide synthase-positive fibers in the dorsal nerve. The ratio of smooth
muscle to collagen in the corpus cavernosum was significantly improved in TrkA
mAb treatment groups compared to PBS vehicle and IgG control groups. WB confirmed
these biological changes. There was a nonsignificant increase in the average
number of intromissions and ejaculations in the TrkA-mAb group. The study
limitations include small sample size, variability in sexual behavior, lack of
data on the neuromuscular mechanism involved, and lack of information of the role
of neurotrophins or cytokines in regeneration. CONCLUSIONS: TrkA-mAb successfully
inhibits sympathetic nerve regeneration, leads to parasympathetic nerve
regeneration, and has therapeutic effects on ED and sexual behavior disorder in a
rat model of CNI. PATIENT SUMMARY: This report provides strong evidence that a
neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb)
inhibits sympathetic nerve regeneration, leads to parasympathetic nerve
regeneration, and has therapeutic effects on erectile dysfunction and sexual
behavior disorder in a rat model of cavernous nerve injury. The results raise the
possibility that human patients with neurogenic erectile dysfunction may respond
to TrkA-mAb in a manner that parallels the response seen in our rodent study.
PMID- 25847858
TI - A review of the literature and proposed classification on e-prescribing:
Functions, assimilation stages, benefits, concerns, and risks.
AB - BACKGROUND: Evidence from the literature indicates that besides its benefits, e
prescribing also generates new types of unintended medication errors that have
the potential to harm patient safety. Analyzing both the benefits and risks of e
prescribing can give health care organizations a better understanding of the
improvements gained and errors generated by this technology. OBJECTIVES: To
review the primary functions of e-prescribing and its assimilation stages in the
health care context. This review also aims to classify the potential benefits,
risks and concerns associated with e-prescribing along with factors contributing
to e-prescribing errors. METHODS: A literature review was conducted primarily in
Web of Sciences electronic databases. The online databases were searched for both
peer-reviewed quantitative and qualitative research papers written in English and
published between January 2008 and December 2014 (i.e., the last seven years).
Several additional studies were also accessed through Google Scholar and the
citations of the selected articles. A total of 73 publications met the study's
inclusion criteria. RESULTS: The key benefits of e-prescribing were identified as
improving the quality of health care services, increasing the efficiency and
effectiveness of prescribing and dispensing medications, reducing medication
errors, and health care cost savings. Failure to properly implement e-prescribing
systems can also result in new types of errors that reduce workflow efficiency,
increase medication cost, and threaten patient safety. In this study, factors
contributing to potential errors were categorized into four primary groups
(human, technical, interaction and organizational errors). CONCLUSIONS: This
review identified the primary benefits and risks of e-prescribing services. The
study contributes to the body of knowledge related to the design, adoption and
use of e-prescribing by providing a clear reflection on its potential gains and
risks. Based on the findings of this review, conducting research in several areas
is quite promising as future work. This review also has practical implications
for health care providers, e-prescribing software vendors and policy makers.
PMID- 25847859
TI - Evaluation of natural radioactivity content in high-volume surface water samples
along the northern coast of Oman Sea using portable high-resolution gamma-ray
spectrometry.
AB - Portable high-resolution gamma-ray spectrometry was carried out to determine the
natural radioactivity levels in high volume surface water samples of the northern
coast of Oman Sea, covering the coastal strip from Hormoz strait to Goatr
seaport, for the first time. The water samples from 36 coastal and near shore
locations were collected for analysis. Analyses on the samples collected were
carried out to determine (226)Ra, (232)Th and (40)K contents. The concentration
of (226)Ra, (232)Th and (40)K in surface water samples ranged between 2.19 and
2.82 Bq/L, 1.66-2.17 Bq/L and 132.6-148.87 Bq/L, respectively. The activity
profile of radionuclides shows low activity across the study area. The study also
examined some radiation hazard indices. The external hazard index was found to be
less than 1, indicating a low dose. The results of measurements will serve as
background reference level for Oman Sea coastlines.
PMID- 25847860
TI - Influence of precipitation on (7)Be concentrations in air as measured by CTBTO
global monitoring system.
AB - Data collected by the International Monitoring System (IMS) during 2009-2012 were
used to study influence of precipitation and relative humidity on changes in
(7)Be concentrations in atmosphere. The significant decrease in (7)Be
concentrations, corresponding to measurements collected by stations located
within Intertropical Convergence Zone (ITCZ) is demonstrated. This effect can be
attributed to the process of enhanced wet deposition within the ITCZ. To quantify
this effect data collected by IMS stations within ITCZ were thoroughly analyzed.
It was found that the atmospheric content of (7)Be strongly decreases under the
rain conditions. The rain mediated depletion of (7)Be to half of its before rain
value, needs about 62 h in case of light precipitation, while in the case of
moderate precipitation about 38 h is needed. In addition the evaluated impact of
humidity showed that increase in relative humidity by 20%, for example from 70%
+/- 5% to 90% +/- 5% causes almost a double decrease in beryllium concentration
in surface air.
PMID- 25847861
TI - Effects of active music therapy on the normal brain: fMRI based evidence.
AB - The aim of this study was to investigate the neurophysiological bases of Active
Music Therapy (AMT) and its effects on the normal brain. Twelve right-handed,
healthy, non-musician volunteers were recruited. The subjects underwent 2 AMT
sessions based on the free sonorous-music improvisation using rhythmic and
melodic instruments. After these sessions, each subject underwent 2 fMRI scan
acquisitions while listening to a Syntonic (SP) and an A-Syntonic (AP) Production
from the AMT sessions. A 3 T Discovery MR750 scanner with a 16-channel phased
array head coil was used, and the image analysis was performed with Brain Voyager
QX 2.8. The listening to SP vs AP excerpts mainly activated: (1) the right middle
temporal gyrus and right superior temporal sulcus, (2) the right middle frontal
gyrus and in particular the right precentral gyrus, (3) the bilateral precuneus,
(4) the left superior temporal sulcus and (5) the left middle temporal gyrus.
These results are consistent with the psychological bases of the AMT approach and
with the activation of brain areas involved in memory and autobiographical
processes, and also in personal or interpersonal significant experiences. Further
studies are required to confirm these findings and to explain possible effects of
AMT in clinical settings.
PMID- 25847862
TI - Curcumin induces the apoptosis of non-small cell lung cancer cells through a
calcium signaling pathway.
AB - Curcumin is known for its anti-proliferative effects in lung cancer cells.
Studies have demonstrated that an increase in the levels of intracellular free
calcium ([Ca2+]i) is involved in curcumin-induced apoptosis. In this study, we
aimed to investigate the involvement of calcium overload in the anti
proliferative effects of curcumin on lung cancer cells and the possible
mechanisms involved. A549 and H1299 lung cancer cells were incubated with serial
diluted curcumin. MTT assay was used to assess the cytotoxic effects of curcumin
on the lung cancer cells; the inositol 1,4,5-trisphosphate receptor (IP3R, a key
regulator of [Ca2+]i signaling) was blocked by its specific inhibitor,
xestospongin C (XSC). Hoechst 33342, Fura-2/AM and rhodamine 123 fluorescence
staining was employed to detect the apoptosis, the [Ca2+]i level and
mitochondrial potential in the lung cancer cells. The expression levels of B-cell
lymphoma-2 (Bcl-2), cleaved caspase-3 and cleaved caspase-9, and the
phosphorylation level of IP3R were evaluated by western blot analysis. Our
results revealed that curcumin inhibited cell growth, increased the [Ca2+]i level
and increased the apoptosis of the lung cancer cells in a concentration-dependent
manner. However, XSC attenuated the increase in the [Ca2+]i level and apoptosis,
and also reversed the curcumin-induced loss of mitochondrial potential potential.
Treatment with curcumin downregulated the expression of Bcl-2, and elevated the
phosphorylation level of IP3R in a concentration-dependent manner. However, this
effect was not reversed by treatment with XSC. In conclusion, the cytotoxic
effects of curcumin on lung cancer cells were induced by calcium overload, which
involves Bcl-2 mediated IP3R phosphorylation.
PMID- 25847863
TI - Construction of helical coordination polymers via flexible conformers of bis(3
pyridyl)cyclotetramethylenesilane: metal(ii) and halogen effects on luminescence,
thermolysis and catalysis.
AB - Infinite rectangular-tubular helices, [MX2L] (M = Zn(ii), Hg(ii); X(-) = Cl(-),
Br(-); L = bis(3-pyridyl)cyclotetramethylenesilane), have been efficiently
constructed via the combined effects of the potential flexible conformers of L
and the tetrahedral geometry of M(ii) ions. This helical molecular system affords
a racemic mixture of P- and M-helices in a crystal. The helical pitches
(7.8934(4)-8.1560(2) A) that are sensitive to the nature of M(ii) ions and halide
anions are attributable to subtle change in the flexible dihedral angles between
the two pyridyl groups around Si and the M(ii) hinges. Their photoluminescence
intensities, correspondingly, are in the order [ZnCl2L] > [ZnBr2L] ? [HgCl2L] >
[HgBr2L]. Zinc(ii) complexes show recyclable catalytic effects on the
transesterification reaction in the order [ZnCl2L] > [ZnBr2L]. Calcination of
[ZnCl2L] and [ZnBr2L] at 500 degrees C produces uniform hexagonal tubular spire
crystals of 1.2 * 1.2 * 4.0 MUm(3) dimensions and spheres, respectively.
PMID- 25847864
TI - Graphene-encapsulated silica as matrix solid-phase dispersion extraction sorbents
for the analysis of poly-methoxylated flavonoids in the leaves of Murraya
panaculata (L.) Jack.
AB - In this study, graphene-encapsulated silica was synthesized by a hydrothermal
reduction strategy. The presence of silica in graphene was identified by Fourier
transform infrared spectrometry, X-ray diffraction and scanning electron
microscopy. The graphene-encapsulated silica subsequently was used as adsorbent
for matrix solid-phase dispersion extraction of poly-methoxylated flavonoids from
the dried leaves of Murraya panaculata (L.) Jack. Compared with the other
adsorbents (graphene, silica gel, C18 silica, neutral alumina, diatomaceous
earth) and without any adsorbents, better results were obtained. Then a method
for analysis of poly-methoxylated flavonoids was established by coupling matrix
solid-phase dispersion extraction with ultra high performance liquid
chromatography and UV detection. Compared with reflux extraction and ultrasonic
extraction, the proposed method is quicker, more efficient and more environmental
protection. Less than 10 min is needed from extraction to detection.
PMID- 25847865
TI - Diversity and Phylogeny of Gymnodiniales (Dinophyceae) from the NW Mediterranean
Sea Revealed by a Morphological and Molecular Approach.
AB - The diversity and phylogeny of dinoflagellates belonging to the Gymnodiniales
were studied during a 3-year period at several coastal stations along the Catalan
coast (NW Mediterranean) by combining analyses of their morphological features
with rDNA sequencing. This approach resulted in the detection of 59 different
morphospecies, 13 of which were observed for the first time in the Mediterranean
Sea. Fifteen of the detected species were HAB producers; four represented novel
detections on the Catalan coast and two in the Mediterranean Sea. Partial rDNA
sequences were obtained for 50 different morphospecies, including novel LSU rDNA
sequences for 27 species, highlighting the current scarcity of molecular
information for this group of dinoflagellates. The combination of morphology and
genetics allowed the first determinations of the phylogenetic position of several
genera, i.e., Torodinium and many Gyrodinium and Warnowiacean species. The
results also suggested that among the specimens belonging to the genera
Gymnodinium, Apicoporus, and Cochlodinium were those representing as yet
undescribed species. Furthermore, the phylogenetic data suggested taxonomic
incongruences for some species, i.e., Gyrodinium undulans and Gymnodinium
agaricoides. Although a species complex related to G. spirale was detected, the
partial LSU rDNA sequences lacked sufficient resolution to discriminate between
various other Gyrodinium morphospecies.
PMID- 25847866
TI - Different utilization of alginate and other algal polysaccharides by marine
Alteromonas macleodii ecotypes.
AB - The marine bacterium Alteromonas macleodii is a copiotrophic r-strategist, but
little is known about its potential to degrade polysaccharides. Here, we studied
the degradation of alginate and other algal polysaccharides by A. macleodii
strain 83-1 in comparison to other A. macleodii strains. Cell densities of strain
83-1 with alginate as sole carbon source were comparable to those with glucose,
but the exponential phase was delayed. The genome of 83-1 was found to harbour an
alginolytic system comprising five alginate lyases, whose expression was induced
by alginate. The alginolytic system contains additional CAZymes, including two
TonB-dependent receptors, and is part of a 24 kb genomic island unique to the A.
macleodii 'surface clade' ecotype. In contrast, strains of the 'deep clade'
ecotype contain only a single alginate lyase in a separate 7 kb island. This
difference was reflected in an eightfold greater efficiency of surface clade
strains to grow on alginate. Strain 83-1 furthermore hydrolysed laminarin,
pullulan and xylan, and corresponding polysaccharide utilization loci were
detected in the genome. Alteromonas macleodii alginate lyases were predominantly
detected in Atlantic Ocean metagenomes. The demonstrated hydrolytic capacities
are likely of ecological relevance and represent another level of adaptation
among A. macleodii ecotypes.
PMID- 25847867
TI - Effect of hyperbaric oxygen therapy on amphotericin-B induced acute renal failure
in rats.
AB - AIM: Acute renal injury may occur after amphotericin B (AmB) administration. The
hypothesized injury mechanism is renal vasoconstriction and direct toxic damage.
Hyperbaric oxygen therapy (HBO) is indicated for treatment of many ischemic
events but not for acute renal failure (ARF). The aim of this study was to
investigate the role of HBO therapy in AmB induced ARF. METHODS: ARF was induced
in 41 Sprague-Dawley rats by a single dose of 75 mg/kg AmB. The rats were
randomly divided into two groups; one group was treated with daily HBO for 3
consecutive days. The control group received no HBO treatment. Parameters of
renal function were taken on the 5th day after AmB administration. RESULTS: Forty
one rats were treated with AmB, 21 received HBO and 20 served as controls. Body
weight loss following the administration of AmB was 13.5+14.7% in the HBO treated
rats, as opposed to 24.6+5% in the control group (P=0.004). Serum creatinine and
urea were 0.49+0.13 mg/dL and 200.63+87.82 mg/dL in the treatment group and
0.70+0.22 mg/dL and 368.01+169.35 mg/dL, respectively in the control (P=0.001).
CONCLUSION: In this model of AmB-induced ARF, HBO treatment alleviated renal
injury as reflected by changes in serum creatinine and urea levels.
PMID- 25847868
TI - Continuous intravenous infusion of furosemide is more effective and safer than
coadministration of albumin and furosemide in patients with nephrotic syndrome.
PMID- 25847869
TI - The early recovery of continence after retropubic radical prostatectomy is
possible: preservation of the smooth muscular internal (vescical) sphincter and
of the proximal urethra.
PMID- 25847870
TI - The cytosol must flow: intercellular transport through plasmodesmata.
AB - Plant cells are connected across cell walls by nanoscopic channels called
plasmodesmata (PD), which allow plant cells to share resources and exchange
signaling molecules. Several protein components of PD membranes have been
identified, and recent advances in superresolution live-cell microscopy are
illuminating PD ultrastructure. Restricting transport through PD is crucial for
morphogenesis, since hormones and hundreds of transcription factors regularly
move through PD, and this transport must stop to allow cells to begin
differentiating. Chloroplasts and mitochondria regulate PD function through
signal transduction networks that coordinate plant physiology and development.
Recent discoveries on the relationships of land plants and their algal relatives
suggest that PD have evolved independently in several lineages, emphasizing the
importance of cytosolic bridges in multicellular biology.
PMID- 25847871
TI - In regard to "Risk of second non-breast cancer after radiotherapy for breast
cancer: A systematic review and meta-analysis of 762,468 patients".
PMID- 25847872
TI - Genome-wide comparative analysis of digital gene expression tag profiles during
maize ear development.
AB - The present study profiled and analyzed gene expression of the maize ear at four
key developmental stages. Based on genome-wide profile analysis, we detected
differential mRNA of maize genes. Some of the differentially expressed genes
(DEGs) were predicted to be potential candidates of maize ear development.
Several well-known genes were found with reported mutant analyses, such as,
compact plant2 (ct2), zea AGAMOUS homolog1 (zag1), bearded ear (bde), and silky1
(si1). MicroRNAs such as microRNA156 were predicted to target genes involved in
maize ear development. Antisense transcripts were widespread throughout all the
four stages, and are suspected to play important roles in maize ear development.
Thus, identification and characterization of important genes and regulators at
all the four developmental stages will contribute to an improved understanding of
the molecular mechanisms responsible for maize ear development.
PMID- 25847873
TI - Structural and evolutionary divergence of cyclic nucleotide binding domains in
eukaryotic pathogens: Implications for drug design.
AB - Many cellular functions in eukaryotic pathogens are mediated by the cyclic
nucleotide binding (CNB) domain, which senses second messengers such as cyclic
AMP and cyclic GMP. Although CNB domain-containing proteins have been identified
in many pathogenic organisms, an incomplete understanding of how CNB domains in
pathogens differ from other eukaryotic hosts has hindered the development of
selective inhibitors for CNB domains associated with infectious diseases. Here,
we identify and classify CNB domain-containing proteins in eukaryotic genomes to
understand the evolutionary basis for CNB domain functional divergence in
pathogens. We identify 359 CNB domain-containing proteins in 31 pathogenic
organisms and classify them into distinct subfamilies based on sequence
similarity within the CNB domain as well as functional domains associated with
the CNB domain. Our study reveals novel subfamilies with pathogen-specific
variations in the phosphate-binding cassette. Analyzing these variations in light
of existing structural and functional data provides new insights into ligand
specificity and promiscuity and clues for drug design. This article is part of a
Special Issue entitled: Inhibitors of Protein Kinases.
PMID- 25847874
TI - Analysis on the expression and function of syndecan in the Pacific white shrimp
Litopenaeus vannamei.
AB - Syndecan is considered to be a multifunctional protein which functions as a cell
surface receptor involved in cell adhesion, migration, cytoskeleton organization
and differentiation. Previous bioinformatic analysis has revealed that syndecan
in shrimp might interact with white spot syndrome virus (WSSV). In the present
study, we experimentally studied the function of syndecan in shrimp immunity. The
syndecan from Litopenaeus vannamei (LvSDC) was cloned and analyzed. The full
length cDNA of LvSDC was 1005 bp, consisting of 59 bp 5'-UTR, 253 bp 3'-UTR, and
693 bp open reading frame encoding 230 amino acids. LvSDC consisted of an
extracellular domain (ED), a transmembrane domain (TM) and a cytoplasmic domain
(CD). TM and CD shared high similarities with those of syndecan proteins from
other species. LvSDC was ubiquitously expressed in all tested tissues, with the
highest level in Oka. After WSSV challenge, the transcription level of LvSDC in
Oka was apparently up-regulated. Recombinant LvSDC protein and its rabbit
polyclonal antibody were prepared for detecting the location of LvSDC in
hemocytes using immunocytochemistry approach. Data showed that LvSDC mainly
located at the cell membrane and the cytoplasm of hemocytes. After silencing of
LvSDC with siRNA, the WSSV copy numbers and mortality of shrimp after WSSV
infection were both significantly decreased. These data provide useful
information for understanding the immune mechanism of shrimp to WSSV infection.
PMID- 25847875
TI - Identification and functional characterization of grass carp IL-17A/F1: An
evaluation of the immunoregulatory role of teleost IL-17A/F1.
AB - In mammals, IL-17A and IL-17F are hallmark cytokines of Th17 cells which act
significant roles in eradicating extracellular pathogens. IL-17A and IL-17F
homologs nominated as IL-17A/F1-3 have been revealed in fish and their functions
remain largely undefined. Here we identified and characterized grass carp IL
17A/F1 (gcIL-17A/F1) in fish immune system. In this regard, both tissue
distribution and inductive expression of gcIL-17A/F1 indicated its possible
involvement in immune response. Moreover, recombinant gcIL-17A/F1 (rgcIL-17A/F1)
was prepared and displayed an ability to enhance pro-inflammatory cytokines (IL
1beta, TNF-alpha and IL-6) mRNA expression in head kidney leukocytes. It is
suggestive of that gcIL-17A/F1 may act as a proinflammatory cytokine in fish
immunity. Besides, rgcIL-17A/F1 induced gene expression and protein release of
grass carp chemokine CXCL-8 (gcCXCL-8) in head kidney cells (HKCs), probably via
NF-kappaB, p38 and Erk1/2 pathways. In particular, culture medium from the HKCs
treated by rgcIL-17A/F1 could stimulate peripheral blood leukocytes migration and
immunoneutralization of endogenous gcCXCL-8 could partially attenuate this
stimulation, suggesting that rgcIL-17A/F1 could recruit immune cells through
producing gcCXCL-8 as mammalian IL-17 A and F. Taken together, we not only
identified the pro-inflammatory role of gcIL-17A/F1 in host defense, but also
provided the basis for clarifying Th17 cells in teleost.
PMID- 25847877
TI - Noninvasive investigation of exocrine pancreatic function: Feasibility of cine
dynamic MRCP with a spatially selective inversion-recovery pulse.
AB - PURPOSE: To investigate the feasibility of noncontrast-enhanced cine dynamic
magnetic resonance cholangiopancreatography (MRCP) with a spatially selective
inversion-recovery (IR) pulse for evaluating exocrine pancreatic function in
comparison with the N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test as a
pancreatic exocrine function test. MATERIALS AND METHODS: Twenty subjects with or
without chronic pancreatitis were included. MRCP with a spatially selective IR
pulse was repeated every 15 seconds for 5 minutes to acquire a total of 20 images
(cine-dynamic MRCP). The median and mean frequency of the observation (the number
of times) and the moving distance (mean secretion grading scores) of pancreatic
juice inflow on cine-dynamic MRCP were compared with a BT-PABA test. RESULTS: The
urinary PABA excretion rate (%) had significant positive correlations with both
the mean secretion grade (r = 0.66, P = 0.002) and frequency of secretory inflow
(r = 0.62, P = 0.004) in cine dynamic MRCP. Both the mean frequency of
observations of pancreatic secretory inflow (1.4 +/- 1.6 times vs. 14.3 +/- 4.2
times, P < 0.001) and the mean secretion grade (grade = 0.16 +/- 0.24 vs. grade =
1.81 +/- 0.81, P < 0.001) was significantly lower in the chronic pancreatitis
group than in the normal subject group. CONCLUSION: Cine dynamic MRCP with a
spatially selective IR pulse may have potential for estimating the pancreatic
exocrine function noninvasively as a substitute for the BT-PABA test.
PMID- 25847876
TI - MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety
related traits.
AB - Regulator of G-protein Signaling 2 (RGS2) is a key regulator of G-protein-coupled
signaling pathways involved in fear and anxiety. Data from rodent models and
genetic analysis of anxiety-related traits and disorders in humans suggest down
regulation of RGS2 expression to be a risk factor for anxiety. Here we
investigated, whether genetic variation in microRNAs mediating
posttranscriptional down-regulation of RGS2 may be a risk factor for anxiety as
well. 75 microRNAs predicted to regulate RGS2 were identified by four
bioinformatic algorithms and validated experimentally by luciferase reporter gene
assays. Specificity was confirmed for six microRNAs (hsa-miR-1271-5p, hsa-miR-22
3p, hsa-miR-3591-3p, hsa-miR-377-3p, hsa-miR-4717-5p, hsa-miR-96-5p) by
disrupting their seed sequence at the 3' untranslated region of RGS2. Hsa-miR
4717-5p showed the most robust effect on RGS2 and regulated two other candidate
genes of anxiety disorders (CNR1 and IKBKE) as well. Two SNPs (rs150925,
rs161427) within and 1,000 bp upstream of the hostgene of hsa-miR-4717-5p
(MIR4717) show a minor allele frequency greater than 0.05. Both were in high
linkage disequilibrium (r(2) = 1, D' = 1) and both major (G) alleles showed a
trend for association with panic disorder with comorbid agoraphobia in one of two
patient/control samples (combined n(patients) = 497). Dimensional anxiety traits,
as described by Anxiety Sensitivity Index (ASI) and Agoraphobic Cognitions
Questionnaire (ACQ) were significantly higher among carriers of both major (G)
alleles in a combined patient/control sample (n(combined) = 831). Taken together,
data indicate that MIR4717 regulates human RGS2 and contributes to the genetic
risk towards anxiety-related traits.
PMID- 25847878
TI - [Which health systems are capable to fight Ebola and other emergencies in Sub
Saharan Africa].
PMID- 25847879
TI - [AIDS research in the South].
PMID- 25847880
TI - [Evaluation of a new polyvalent antivenom against snakebite envenomation
(Inoserp(r) Panafricain) in two different epidemiological settings: Northern
Benin and Maritime Guinea].
AB - OBJECTIVES: The authors evaluated the safety and efficacy of Inoserp((r)) Pan
Africa, a new polyvalent antivenom composed of highly purified and lyophilized
fragments of F(ab')2 immunoglobulins, recently registered in Benin and Guinea.
METHODS: We treated 100 patients in northern Benin (Atacora) and 109 in Maritime
Guinea (Kindia) with confirmed envenomation. Treatment consisted of intravenous
administration of 1 vial for uncomplicated envenomation, and 2 vials for
hemorrhagic or neurotoxic envenomation. The dose was repeated when bleeding or
signs of neurotoxicity persisted or appeared. RESULTS: In Atacora, on arrival at
the hospital, 90% of patients had incoagulable blood, and 50% were bleeding. The
resolution of these bleeding disorders was obtained in less than 3 hours for 50%
of the patients and in less than 24 hours for 98%. Four patients died. In Kindia,
96 patients (88%) presented viper bites with pain + edema and 13 (12 %) others
showed elapid (ptosis, dyspnea) envenomation. One patient bitten by a member of
the Elapidae family, died despite early treatment. In Benin, protocol deviations
for 60% of patients led to significant underdosing of the antivenom; the
proportion was much lower (2%) in Guinea. Signs of intolerance after Inoserp((r))
Pan Africa administration were reported in 8% of patients. All these symptoms
were mild and disappeared rapidly after an antihistamine or corticosteroid
treatment. CONCLUSION: Treatment using intravenous Inoserp((r)) Pan Africa
appeared to be well tolerated and effective against snakebite envenomation in
both epidemiological settings.
PMID- 25847882
TI - [Children hospitalized with severe malaria in Kinshasa (Democratic Republic of
the Congo): Household characteristics and factors associated with mortality].
AB - BACKGROUND: Malaria is a major health problem in tropical Africa. In DRC, little
is known about the characteristics of households of children with severe malaria
or the factors associated with its lethality, especially relative to hospital
status. METHODS: This study of 9 hospitals of the city-province of Kinshasa
studied 1350 children younger than 15 years and hospitalized for severe malaria
from January to November 2011. RESULTS: More than three quarters of children
admitted to public (state) and church hospitals were from poor households and
with uneducated mothers (P < 0.001). The case-fatality rate (5.9% of all
children) differed according to hospital status: 5.3% in state hospitals, 8.4% in
private hospitals, and 4.0% in the faith-based hospitals (P < 0.001). The risk of
death was significantly associated with circulatory collapse (odds ratio, OR =
10.3), number of associated syndromes >2 (OR = 3.5), z-score of weight-for-age <=
2 (OR = 3.5), delay in seeking medical care (OR = 4.9), body temperature >=40
degrees C (OR = 2.9), respiratory distress (OR = 1.9) and home rental (versus
ownership) a tenant (OR = 2.8), and anorexia was a protective factor (odds ratio
= 0.5). CONCLUSION: Severe cases of malaria are rife in poor households and
periurban residential areas. Orienting prevention, control, and care- according
to the vulnerability of affected households and providing early treatment are
imperative if we are to reduce mortality from malaria.
PMID- 25847881
TI - [The impact of urbanization on malaria infection rate and parasite density in
children in the municipality of Yopougon, Abidjan (Cote d'Ivoire)].
AB - From September 23-30, 2005, we conducted a cross-sectional study in six townships
of Yopougon, a municipality of Abidjan. These townships were grouped in three
levels of urbanization (village, precarious township, and residential township).
The main objective of this survey was to determine the impact of urbanization on
the malaria infection (parasite) rate and parasite density, and their
consequences on the heterogeneity of malaria transmission in urban Abidjan.
Specifically we compared these rates in all three urbanization levels, selecting
two townships for each level to take environmental specificities observed from
previous data into account. The study included 400 households per township. All
children younger than 5 years in these households were included. Thick and thin
blood smears were taken for each child on slides, and each slide was examined by
microscope after staining. The malaria infection rate was 21.8%, indicating
mesoendemic malaria. Its distribution varied significantly between the three
urbanization levels. Malaria parasite densities also varied significantly between
them. These results confirm the involvement of urbanization in the heterogeneity
of malaria transmission in the city of Abidjan.
PMID- 25847883
TI - [88 years of cutaneous leishmaniasis in Morocco].
AB - Leishmaniasis in its cutaneous form is a public health problem in Morocco. The
objectives of this study were to assess the development of its epidemiological
profile, identify the relevant species, and determine the location of the
identified cases and their distribution by year, by sex, and by age. This
retrospective epidemiological study covers a period of 88 years and concerns all
reported cases of cutaneous leishmaniasis (CL) in Morocco from the first
description in 1922 until 2010. During this period, 56,194 cases have been
reported; they account for 95.7% of all cases of leishmaniasis (n = 58,710). The
endemicity of CL has changed over time. The increase in its incidence is likely
to be explained both by improved reporting and by a real increase in the number
of cases.
PMID- 25847884
TI - Comparisons of the results of peripheral nerve defect repair with fibrin conduit
and autologous nerve graft: An experimental study in rats.
AB - INTRODUCTION: The standard treatment for nerve defects is nerve autograft. There
is no conduit available that provides the same regenerative capacity of nerve
autograft. This study evaluated the histological and functional recovery of nerve
defects treated with fibrin conduit in comparison to the nerve autograft, in a
rat model. METHOD: A sciatic nerve injury model (10-mm defect) was performed in
20 Wistar rats, nerve defect was reconstructed using a fibrin conduit (n = 10). A
nerve autograft was used as control (n = 10). The walking behavior was measured
by footprint analysis at 4, 8, and 12 weeks and sciatic function index was
determined. After 12 weeks, histological analysis was performed to evaluate the
regenerated nerve and measured axonal density. The triceps surae muscle weight
was also evaluated. RESULTS: The fibrin conduit group showed less improvement in
walking behavior compared to nerve autograft (-53 +/- 2 vs. -36 +/- 2; P < 0.001
at 12 weeks). The fibrin conduit group presented axonal density of 40.0
axons/10.995MUm2 and the nerve autograft group had 67.2 axons/10.995MUm2 (P <
0.001). The triceps surae muscle weight ratio of the fibrin conduit group was 41
+/- 3% versus 71 +/- 4% of the nerve autograft group (P < 0.001). CONCLUSION: The
fibrin conduit could be used for nerve reconstruction following peripheral nerve
injury in the rat model. However, the functional recovery in the fibrin conduit
repair group was worse than that in nerve autograft group and the nerve repair
with the fibrin conduit has less myelinated fibers when compared to the repair
with nerve autograft.
PMID- 25847886
TI - How life history influences the responses of the clam Scrobicularia plana to the
combined impacts of carbamazepine and pH decrease.
AB - In the present study, the bivalve Scrobicularia plana, collected from two
contrasting areas (pristine location and mercury contaminated area), was selected
to assess the biochemical alterations imposed by pH decrease, carbamazepine (an
antiepileptic) and the combined effect of both stressors. The effects on
oxidative stress related biomarkers after 96 h exposure revealed that pH decrease
and carbamazepine induced alterations on clams, with greater impacts on
individuals from the contaminated area which presented higher mortality, higher
lipid peroxidation and higher glutathione S-transferase activity. These results
emphasize the risk of extrapolating results from one area to another, since the
same species inhabiting different areas may be affected differently when exposed
to the same stressors. Furthermore, the results obtained showed that, when
combined, the impact of pH decrease and carbamazepine was lower than each
stressor acting alone, which could be related to the defence mechanism of valves
closure when bivalves are under higher stressful conditions.
PMID- 25847887
TI - Venous leakage treatment revisited: pelvic venoablation using aethoxysclerol
under air block technique and Valsalva maneuver.
AB - OBJECTIVE: We evaluated the effectiveness of pelvic vein embolization with
aethoxysclerol in aero-block technique for the treatment of impotence due to
venous leakage in men using sildenafil for intercourse. The aim of the procedure
was to reduce the use of sildenafil. METHODS: A total of 96 patients with veno
occlusive dysfunction, severe enough for the need of PDE5 inhibitors for vaginal
penetration, underwent pelvic venoablation with aethoxysclerol. The mean patient
age was 53.5 years. Venous leaks were identified by Color Doppler Ultrasound
after intracavernous alprostadil injection. Under local anesthesia a 20-gauge
needle was inserted into the deep dorsal penile vein. The pelvic venogram was
obtained through deep dorsal venography. Aethoxysclerol 3% as sclerosing agent
was injected after air-block under Valsalva manoeuver. Success was defined as the
ability to achieve vaginal insertion without the aid of any drugs, vasoactive
injections, penile prosthesis, or vacuum device. Additionally, a pre- and post-
therapy IIEF score and a digital overnight spontaneous erections protocol (OSEP)
with the NEVATM-system was performed. RESULTS: At 3 month follow-up 77 out of 96
patients (80.21%) reported to have erections sufficient for vaginal insertion
without the use of any drug or additional device. Four (4.17%) patients did not
report any improvement. Follow up with color Doppler ultrasound revealed a new or
persistent venous leakage in 8 (8.33%) of the patients. No serious complications
occurred. CONCLUSIONS: Our new pelvic venoablation technique using aethoxysclerol
in air-block technique was effective, minimally invasive, and cost-effective. All
patients were able to perform sexual intercourse without the previously used
dosage of PDE5 inhibitor. This new method may help in patients with contra
indications against PDE5 inhibitors, in patients who cannot afford the frequent
usage of expensive oral medication or those who do not fully respond to PDE5
inhibitors.
PMID- 25847888
TI - Tubular ectasia of the rete testis (TERT). Differential diagnosis of cystic
testicular disorders.
AB - The ultrasound scan plays an essential role in the urological-andrological
diagnosis. High-resolution transducers (8-15 MHz) make it possible to prove
increasingly small changes. The assessment of cystic masses in the testis can
also be difficult for experienced doctors. However, a precise diagnosis is
crucial for the patient to avoid further invasive diagnostics and therapy. The
differential diagnosis of benign intra-testicular cystic lesions include the
tubular ectasia of the rete testis (TERT), the cystic dysplasia, epidermoid
cysts, dermoid cysts, simple testicular cysts and cysts of the tunica albuginea.
Malign testicular tumours with cystic changes are particularly the mature
teratoma, carcinomas of the epididymis and metastasis. The following overview
shows different sonographic images and interpretations with a particular focus on
TERT.
PMID- 25847889
TI - Sexual dysfunctions after transurethral resection of the prostate (TURP):
evidence from a retrospective study on 264 patients.
AB - OBJECTIVES: Benign prostatic hyperplasia (BPH) and sexual dysfunctions are
diseases with a high prevalence in aged men. Several studies have found a link
between BPH and LUTS resulting from deterioration in sexual function in men aged
50 years and older for whom TURP is considered the gold standard. The impact of
TURP on sexual functions still remain uncertain, nor is it clear what
pathophysiological mechanism underlying the emergence of new episodes of Erectile
Dysfunction (ED) following TURP in patients with normal sexual function before
surgery, while retrograde ejaculation and ejaculate volume reduction represent a
clear side effect; derived from BPH treatment. The aim of this study was to
retrospectively evaluate the effects of transurethral resection of the prostate
(TURP) on sexual function in patients operated in the period 2008-2012 at the
Department of Urology of the University Hospital P. Giaccone, and at Villa Sofia
Cervello Hospital- Palermo. Secondary objective was to reconnect the sample data
to interventional practice and international standards. MATERIALS AND METHODS:
The retrospective longitudinal study was conducted on 264 of the 287 recruitable
patients, aged between 50 and 85 years, suffering from BPH who underwent to TURP
in the period 2008-2012. Telephone interviews were conducted and the
International Index of Erectile Function (IIEF) was administered to assess sexual
function. Patients enrolled were asked to respond to the test by referring at
first to their sexual status in the period before surgery and subsequently to the
state of their sexual function after treatment so as to obtain, for each patient,
a pre- and post-TURP questionnaire in order to get comparisons that corresponding
to reality and to avoid overestimation of the dysfunctional phenomenon. RESULTS:
In the pre-TURP, the 94.32% of the sample reported being sexually active, with
good erectile function in 41.3% of cases, ED mild/moderate in 51.5% and complete
ED in 1, 5% of cases; good libido in 62.9% of cases, lack of libido in 31.4% of
cases and absent in 5.7% of cases (the latter data corresponded to patients not
sexually active); to be sexually satisfied in 29.5% of cases, slightly
dissatisfied in 11, 7% of cases, moderately in 35.3% of cases, dissatisfied and
very dissatisfied in 23.5% of cases (of which 17.8% sexually active and 5.7% non
active). In the post-TURP 89.4% of the sample reported being sexually active,
with good erectile function in 39.1% of cases, DE mild/moderate in 46.9% and
complete DE in 4% of cases; good libido in 53.8% of cases, lack of libido in
33.7% of cases and absent in 13.5% of cases (including 1.9% of sexually active
and 10.6% of non-active); to be sexually satisfied in 29.5% of cases, slightly
dissatisfied in 9.5% of cases, moderately in 35.3% of cases, dissatisfied and
very dissatisfied in 17.8% of cases (of which 14.8% sexually active and 10.6%
inactive). Retrograde ejaculation was referred in 47.8% of those sexually active
after TURP (42.8% if we consider the whole sample). CONCLUSIONS: TURP had no
negative impact on erectile function in contrast to ejaculatory function. Of the
109 patients with good erectile function in pre-TURP, 5.8% reported a worsening
of erectile function after TURP. Among the 136 patients with ED moderate/mild pre
TURP 3.7% reported a worsening in the post-TURP, 16.2% reported an improvement,
while 9.5% stopped any sexual activity. In 3.7% of the cases a complete ED was
reported after TURP, while a decline of libido and sexual satisfaction was
detected in all patients with worsening of sexual function. Retrograde
ejaculation was observed in 48% of those sexually active after TURP. Particular
attention has to be paid to the psychological aspects, both before surgery and in
the postoperative period, which may become an important factor in the decline of
sexual activity.
PMID- 25847890
TI - Light-emitting diode exposure enhances sperm motility in men with and without
asthenospermia: preliminary results.
AB - OBJECTIVE: To evaluate the effect of light-emitting diode (LED) on sperm motility
in men with and without asthenospermia. MATERIAL AND METHODS: Semen samples from
27 men were assessed and washed. An aliquot was taken from each sample as a
control. The remaining amount was exposed to red LED for 2, 5 and 10 minutes.
Sperm motility from the test and control tubes were re-checked at the end of each
time interval. In 11 of these 27 samples, the same protocol was repeated without
sperm washing. Evaluation of sperm creatine kinase (CK) activity, hypoosmotic
swelling (HOS) test and aniline blue staining (ANBS) were undertaken after
phototherapy in additional 15 samples. RESULTS: Progressive sperm motility
increased significantly after LED treatment at the different time intervals
whether in washed (p = 0.000) or non-washed (p = 0.003) samples. The amount of
the increase in motility in washed aliquots was significantly more (p = 0.000)
than in naive semen. Sperm CK activity increased, but was not significant whilst
there were no changes regarding HOS and ANBS. CONCLUSION: Red LED is a promising
safe tool to boost sperm motility in vitro. This may have a great implication on
maximizing the possibilities and outcomes of intrauterine insemination trials.
PMID- 25847891
TI - Smoking, diabetes, blood hypertension: possible etiologic role for Peyronie's
disease? Analysis in 279 patients with a control group in Sicily.
AB - OBJECTIVE: To assess the proportion of patients with Peyronie's Disease (PD) and
the possible association with its potential risk factors in the general
population of the central and western Sicily in our weekly andrological
outpatient clinic. MATERIALS AND METHODS: We recruited a sample of 279
consecutive patients consulting our andrological outpatient clinic. Two arms were
created: the first one composed by PD patients (men with symptoms suggestive for
PD), the second one composed by patients with other andrological diseases
(control arm). For each patient we evaluated the age, cigarette smoking,
diabetes, blood hypertension and erectile function. In the PD arm we administered
validated questionnaires to determine the erectile function status by the
International Index of Erectile Function 5 (IIEF-5) and the pain status during
erection by the Visual Analogue Scale (VAS). A univariate analysis was conducted
using R software. RESULTS: We enrolled 279 consecutive patients. The number of PD
patients was 97 (34,7%). The univariate analysis showed a correlation between PD
and cigarette smoking (p = 0.0242), blood hypertension (p < 0.001), erectile
dysfunction (p < 0.001). No significant association was observed between diabetes
and PD (p = 0.358). The median age of PD arm was 60 years and the median age of
the control arm was 63,5 years; therefore the median age of PD arm resulted lower
than the median age of the control arm (p = 0,031). CONCLUSIONS: Peyronie's
disease is more common than we might think; furthermore it can be diagnosed among
young patients. According to our results, cigarette smoking and blood
hypertension may be considered statically significant risk factors for developing
PD. On the contrary diabetes seems not to be a risk factor for PD. According to
our results PD should be sought also in young patients. Further studies are
necessary to confirm that removing the indicated risk factors may reduce the
incidence of PD.
PMID- 25847892
TI - Effectiveness on urinary symptoms and erectile function of Prostamev Plus(r) vs
only extract Serenoa repens.
AB - Prostatic inflammation is widespread in the male population. Two groups of 50
patients each with symptoms of prostatic inflammation and ecocolorDoppler
indicative of prostatitis were identified. Both groups were further subdivided
into two subgroups (respectively A1, A2, B1, and B2). Group A1 underwent therapy
with oral levofloxacin 500 mg daily for 10 days plus co-treatment with oral
Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus(r)) daily for
two months; Group A2 with oral levofloxacin 500 mg daily for 10 days plus oral
Serenoa repens extract 320 mg/day for two months; Group B1 specific antibiotic
treatment for 10 days (included levofloxacin if sensitive) plus co-treatment with
oral Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus(r)) daily
for two months; Group B2 with specific antibiotic treatment for 10 days plus
Serenoa repens 320 mg/day for two months. The groups treated with Prostamev
Plus(r) in comparison to the groups treated with Serenoa repens extract (saw
palmetto) achieved better improvements of both IPSS score, urinary flow and
sexual life.
PMID- 25847893
TI - A conservative approach to perineal Fournier's gangrene.
AB - Fournier's gangrene (FG) is a disease involving necrosis of perineum and external
genitalia; in 95% of cases it is possible to diagnose the Fournier's gangrene
just by physical examination. The clinical presentation of FG varies from an
initial localized infection to large areas with necrotizing infection. The
disease typically affect elderly men (6 degrees -7 degrees decade) with
important systemic comorbidities; women are less frequently affected. Despite
improvements in diagnosis and management, the mortality rate nowadays is between
20% and 43%. The severity and mortality of the disease is dependent upon the
general condition of the patient at presentation and upon the rate of spread of
the infection. Treatment involves a multidisciplinary approach: intensive
systematic management, broad-spectrum antibiotic therapy, early surgical
debridement (wide abscission of necrotic tissues and surgical drainage of
peritoneum, scrotum, penis, and inguinal areas), hyperbaric oxygen therapy;
surgery can eventually be repeated if necessary; reconstructive surgery has an
important role in the final treatment of the disease. The technical difficulties
frequently encountered and the inability to make a complete removal of the
necrotizing tissues at the time of surgery in some cases has led to the
application of combined techniques, in view of the enhancement effect of specific
advanced medications, targeted antibiotic therapy and hyperbaric medicine. We
have considered 6 patients affected by Fournier's gangrene treated at our
institution; all the patients received treatment with the help of plastic
surgeons of the same institution. After debridement, all the patients were
treated with advanced specific dressings consisting of plates and strips made of
calcium alginate, hydrogels and polyurethane and twodimensional cavity foams.
Reconstructive surgery was necessary in one case. Hyperbaric oxygen therapy (HBO)
has been performed in all cases. The multidisciplinary approach, the combined use
of HBO therapy and the adoption of advanced specific dressings, have made
possible the complete healing of the lesions in a shorter period, avoiding
further surgery in 5 out of 6 patients.
PMID- 25847894
TI - Is it possible to predict the need of inguinal lymphadenectomy in patients with
squamous cell carcinoma of the penis? A clinical and a pathological study.
AB - OBJECTIVE: to investigate the role of CD- 44 immunohistochemical expression
within tumoural and non-tumoural tissue, aiming to understand if it can help us
to predict the need of performing inguinal lymph nodes dissection to complete
surgery of the penis. MATERIALS AND METHODS: CD44 immunohistochemical expression
was investigated in tissue specimens from 39 patients with squamous cell
carcinoma of the penis who underwent partial or total penectomy between 1987 and
2008. Patient age, tumour size, and grade; CD44 intensity score, cytological
expression, topographic and distribution pattern were evaluated by
immunohistochemistry on archived material and correlated with disease-specific
survival. RESULTS: mean patients age was 67.7 years; mean followup was 130.44
months. Bilateral inguinal lymphadenectomy was performed in 14 patients; there
were 8 N+ patients (23.5%). pTis-pT1 vs. > pT1 and the EAU classification of risk
group resulted to be predictive of lymph nodal metastases at univariate analysis
(respectively p = 0.006 and p = 0.045), but not the grading. The intensity score,
cytological expression, topographic and distribution pattern of CD44 staining did
not correlate with stage, grade and lymph nodes metastases. All disease related
deaths occurred only in patients showing an high CD44 intratumoral expression,
but this correlation is not statistically significant. Multivariate analysis
showed that only lymph node metastasis was an independent prognostic factor
predictive of lymph nodes metastases. CONCLUSIONS: CD44 expression in patients
with squamous cell carcinoma of the penis is not able to predict the need of
performing inguinal lymphadenectomy; staging and the EAU classification of risk
group resulted to be predictive of lymph nodal metastases.
PMID- 25847895
TI - The effect of inclined position on stone free rates in patients with lower
caliceal stones during SWL session.
AB - OBJECTIVE: To compare the outcomes of shock wave lithotripsy (SWL) combined with
inclined position and SWL alone in patients with lower pole calyx stones.
METHODS: Seven hundred forty patients who underwent SWL treatment for lower pole
renal stones with a total diameter of 2 cm or less were prospectively randomized
into two groups. They were comparable in terms of age, sex, and stone diameters.
Patients with lower calyceal stones (4-20 mm) were randomized to SWL (368
patients) or SWL with simultaneous inclination (372 patients) with 30o head down
Trendelenburg position). Shock wave and session numbers were standardized
according to stone size. Additional standardized shock waves were given to
patients with stone fragments determined by kidney urinary bladder film and
ultrasound at weeks 1, 4, 10. RESULTS: The overall stone free rate (SFR) was 73%
(268/368) in patients with SWL alone and 81% (300/372) in SWL with inclination at
the end of 12th week (p = 0.015). No significant adverse events were noted in
both treatment groups. CONCLUSION: Simultaneous inclination of patients during
SWL session increase SFR in lower caliceal stones significantly compared to SWL
treatment alone.
PMID- 25847896
TI - Comparing robotic, laparoscopic and open cystectomy: a systematic review and meta
analysis.
AB - OBJECTIVE: To conduct a systematic review and meta-analysis comparing outcomes
between Open Radical Cystectomy (ORC), Laparoscopic Radical Cystectomy (LRC) and
Robot-assisted Radical Cystectomy (RARC). RARC is to be compared to LRC and ORC
and LRC compared to ORC. MATERIAL AND METHODS: A systematic review of the
literature was conducted, collating studies comparing RARC, LRC and ORC. Surgical
and oncological outcome data were extracted and a meta-analysis was performed.
RESULTS: Twenty-four studies were selected with total of 2,104 cases analyzed.
RARC had a longer operative time (OPT) compared to LRC with no statistical
difference between length of stay (LOS) and estimated blood loss (EBL). RARC had
a significantly shorter LOS, reduced EBL, lower complication rate and longer OPT
compared to ORC. There were no significant differences regarding lymph node yield
(LNY) and positive surgical margins (PSM.) LRC had a reduced EBL, shorter LOS and
increased OPT compared to ORC. There was no significant difference regarding LNY.
CONCLUSION: RARC is comparable to LRC with better surgical results than ORC. LRC
has better surgical outcomes than ORC. With the unique technological features of
the robotic surgical system and increasing trend of intra-corporeal
reconstruction it is likely that RARC will become the surgical option of choice.
PMID- 25847897
TI - Evaluation of laparoscopic vs robotic partial nephrectomy using the margin,
ischemia and complications score system: a retrospective single center analysis.
AB - OBJECTIVE: To evaluate differences between Laparoscopic Partial Nephrectomy (LPN)
and Robot-Assisted Partial Nephrectomy (RAPN) using the Margin, Ischemia and
Complications (MIC) score system and to evaluate factors related with MIC
success. MATERIALS AND METHODS: Single centre retrospective study on 258 LPN and
58 RAPN performed between January 2012 and January 2014. Success was defined when
surgical margins was negative, Warm Ischemia Time (WIT) was <= 20 minutes and no
major complications occurred. Mann-Whitney-U and Pearson chi2 correlation were
used to compare LPN and RAPN. A matched pair comparison was also performed.
Spearman correlation (Rho) was used to evaluate the relationship between
clinical, intra and post-operative and pathological patients characteristics with
MIC score. A binary regression analysis was also performed to evaluate
independent factors associated with MIC success. RESULTS: The MIC rate in LPN and
RAPN was 55% and 65.5% respectively. No differences in clinical, intra and post
operative outcomes between groups were found. Clinical tumor size (p-value: <
0.001; OR: 0.829; 95% CI: 0.697-0.987), PADUA score (p-value: < 0.001; OR: 0.843;
95% CI: 0.740-0.960), PADUA risk groups (intermediate; p-value: < 0.001; OR:
0.416; 95% CI: 0.238- 0.792; high: p-value: < 0.001; OR: 0.356; 95% CI: 0.199-
0.636), WIT (p-value: < 0.001; OR: 0.598; 95% CI: 0.530- 0.675) were
independently associated with MIC. eGFR (< 60 vs >= 60 ml/min per 1.73 m2: p
value: < 0.001; OR: 3.356; 95% CI: 1.701-6.621) and Fuhrman nuclear grade (p
value: 0.014; OR: 1.798; 95% CI:1.129-2.865) were also independently associated
with MIC. CONCLUSIONS: MIC score system is a simple and useful tool to report and
to compare different surgical approach.
PMID- 25847898
TI - Change of practice patterns in urology with the introduction of the Da Vinci
surgical system: the Greek NHS experience in debt crisis era.
AB - OBJECTIVE: To determine the attitudinal change for urologic surgery in Greece
since the introduction of the da Vinci Surgical System (DVS). We describe
contemporary trends at public hospital level, the initial Greek experience, while
at the same time Greece is in economic crisis and funding is under austerity
measures. MATERIALS AND METHODS: We retrospectively analyzed annualized case log
data on urologic procedures, between 2008 (installation of the DVS) and 2013,
from "Laiko'' Hospital in Athens. We evaluated, using summary statistics, trends
and institutional status regarding robot-assisted surgery (RAS). We also analyzed
the relationship between the introduction of RAS and change in total volume of
procedures performed. RESULTS: 1578 of the urological procedures performed at
"Laiko'' Hospital were pooled, 1342 (85%) being open and 236 RAS (15%). We
observed a 6-fold increase in the number of RAS performed, from 7% of the total
procedural volume (14/212) in 2008 to 30% (96/331) in 2013. For radical
prostatectomy, in 2008 2% were robot-assisted and 98% open while in 2013, 46% and
54% respectively. Pyeloplasty was performed more often using the robot-assisted
method since 2010. RAS-dedicated surgeons increased both RAS and the total number
of procedures they performed. From 86 in 2008 to 145 in 2013, with 57% of them
being RAS in 2013 as compared to 13 % in 2008. CONCLUSIONS: Robot-assisted
surgery has integrated into the armamentarium for urologic surgery in Greece at
public hospital level. Surgical robot acquisition is also associated with
increased volume of procedures, especially prostatectomy, despite the ongoing
debate over cost-effectiveness, during economic crisis and International Monetary
Fund (IFN) era.
PMID- 25847899
TI - Effect of immobilization on urine calcium excretion in orthopedic patients with
pelvic fracture treated by skin traction.
AB - OBJECTIVES: To determine the effects on urine calcium excretion of immobilization
by skin traction in patients with pelvic fracture. METHODS: In a prospective
study, a consecutive series of patients with pelvic fracture treated by skin
traction were enrolled. Serum (calcium, phosphorous, alkaline phosphatase,
sodium, potassium, uric acid, BUN, creatinine) and fasting urine calcium,
creatinine, sodium, potassium and uric acid were checked within 48 hours of
hospitalization and at 7, 14 and 21 days of immobilization and then after 3
months of mobilization. Trends in changes of variables were recorded. RESULTS:
Fifty five patients were enrolled in this study; they were 45 (81.8%) males and
10 (18.2%) females with a mean age 19.4 +/- 12.7 years. We found that serum
levels of calcium (p = 0.004), phosphorous (p = 0.047) and alkaline phosphatase
(p = 0.001) increased significantly during the 3 weeks of immobilization. In the
same way, urine calcium/ urine creatinine ratio increased significantly in the
study period (p = 0.004). No symptomatic renal stone formation was observed
during the study period. CONCLUSIONS: Immobilization even in short term causes
hypercalciuria in orthopedic patients. Although it is transient and improves with
subsequent mobilization, it is needed to be considered specifically by the team
caring for this group of patients.
PMID- 25847900
TI - Use of cinacalcet in nephrolithiasis associated with normocalcemic or
hypercalcemic primary hyperparathyroidism: results of a prospective randomized
pilot study.
AB - OBJECTIVES: To evaluate, by means of a prospective randomized study, the efficacy
of cinacalcet in the forms of nephrolithiasis associated with primary
hyperparathyroidism in both the hypercalcemic and normocalcemic variant.
MATERIALS AND METHODS: Ten patients suffering from active nephrolithiasis
associated with primary hyperparathyroidism (4 hypercalcemics and 6
normocalcemics), equally divided between males and females, were randomly but not
blindly addressed to treatment with potassium citrate and allopurinol, or to the
same therapeutic regimen in combination with cinacalcet. The dosage of cinacalcet
was optimized for each patient in order to obtain a reduction of parathyroid
hormone (PTH) within normal limits while enabling the maintenance of adequate
calcemic values. All study participants were given the same diet based on a
reduction in sodium intake, oxalate-rich foods and animal protein with
standardized intake of calcium and an increase in hydration. After a follow up
period of 10 months , cinacalcet was associated to standard therapy and diet in
patients who were not taken it, conversely cinacalcet was withdrawn in the
remaining patients who remained on standard therapeutic regimen and diet. Follow
up was continued for a second period of observation of the same duration of the
first. RESULTS: At the end of the period of treatment with cinacalcet, for both
variants of hyperparathyroidism, a statistically significant reduction in the
overall number and in the diameter of renal stones was found. CONCLUSIONS: This
prospective randomized study shows the effectiveness of cinacalcet used in
combination with a diet with normalized calcium intake, in reducing the number
and size of urinary stones in hypercalemic and normocalcemic forms of primary
hyperparathyroidism.
PMID- 25847901
TI - Is routine ureteral stenting really necessary after retrograde intrarenal
surgery?
AB - OBJECTIVES: To investigate the situations in which ureteral double-J stent should
be used after retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS:
Patients with no ureteral double-J stent after RIRS constituted Group 1, and
those with double- J stent after RIRS constituted Group 2. Patients' age and
gender, renal stone characteristics (location and dimension), stone-free status,
VAS score 8 hours after surgery, post-procedural renal colic attacks, length of
hospitalization, requirement for re-hospitalization, time to rehospitalization
and secondary procedure requirements were analyzed. RESULTS: RIRS was performed
on 162 renal units. Double-J stent was used in 121 (74.6%) of these after RIRS,
but not in the other 41 (25.4%). At radiological monitoring at the first month
postoperatively after RIRS, complete stone-free status was determined in 122
(75.3%) renal units, while residual stone was present in 40 (24.6%). No
significant differences were observed between the groups in terms of duration of
fluoroscopy (p = 0.142), operation (p = 0.108) or hospitalization times (p =
0.798). VAS values determined routinely on the evening of surgery were
significantly higher in Group 1 than in Group 2 (p = 0.025). Twenty-eight (17.2%)
presentations were made to the emergency clinic due to renal colic within 1 month
after surgery. Double-J catheter was present in 24 (85.7%) of these patients.
CONCLUSIONS: Routine double-J stent insertion after RIRS is not essential since
it increases costs, morbidity and operation time.
PMID- 25847902
TI - Relevance of prostate cancer in patients with synchronous invasive bladder
urothelial carcinoma: a monocentric retrospective analysis.
AB - OBJECTIVES: We retrospectively reviewed data of patients with incidental prostate
cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder
cancer and we analyzed their features with regard to incidence, pathologic
characteristics, clinical significance, and implications for management. MATERIAL
AND METHODS: Clinical data and pathological features of 64 patients who underwent
standard RCP for bladder cancer were included in this study. Besides the
urothelial carcinoma of the urinary bladder, the location and tumor volume of the
PCa, prostate apex involvement, Gleason score, pathological staging and surgical
margins were evaluated. Clinically significant PCa was defined as a tumor with a
Gleason 4 or 5 pattern, stage >= pT3, lymph node involvement, positive surgical
margin or multifocality of three or more lesions. Postoperative follow-up was
scheduled every 3 months in the first year, every 6 months in the second and
third year, annually thereafter. RESULTS: 11 out of 64 patients (17.2%) who
underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as
significant PCa, while 8 cases (72.7%) were clinically insignificant. The
positive surgical margin of PCa was detected in 1 patient with significant
disease. The prostate apex involvement was present in 1 patient of the
significant PCa group. Median follow-up period was 47.8 +/- 29.2 (range 4-79).
During the follow-up, biochemical recurrence occurred in 1 patient (9%).
Concerning the cancer specific survival there was no statistical significance (P
= 0.326) between the clinically significant and clinical insignificant cancer
group. CONCLUSIONS: In line with published studies, incidental PCa does not
impact on the prognosis of bladder cancer of patients undergoing RCP.
PMID- 25847903
TI - Effect of microorganisms on etiology of hematospermia.
AB - BACKGROUND: Hematospermia is the presence of blood in the ejaculate. Its etiology
is congenital, inflammatory, infectious, obstructive, tumoral, vascular,
traumatic, iatrogenic or related to systemic disease. It is a quite irritating
and life-quality-disturbing condition for men. It is significant to demonstrate
infectious-based hematospermia due to the fact that its treatment is easier than
for other reasons. METHODS: 30 patients, having spontaneous hematospermia, were
taken to our study. The serum total PSA levels of the patients were examined and
microbiological examinations such as direct inspection for ejaculate, routine
bacteriological and mycetes culture, Gram staining, trichrome staining and
Mycoplasma hominis/Ureaplasma urealyticum culture (Mycofast Evolution 3, ELITech,
France) were performed. RESULTS: Bacteria was isolated in 11 (36%) of 30 patients
with hematospermia. S.aureus occurred in five patients (45.5%), U.urealyticum in
three patients (27.2%) and E.coli and K.pneumoniae in one each (9.1%).
U.urealyticum and S.aureus occurred together in one patient. No statistical
difference of scores of National Institute of Health-Chronic Prostatitis Symptoms
Index (CPSI) and serum total PSA levels between the patients with and without
infection was observed. CONCLUSIONS: Hematospermia mostly affects micturition
functions of young men and it can be due to infection in one-third of the cases.
PMID- 25847904
TI - Urolithiasis is associated with low serum testosterone levels in men.
AB - OBJECTIVE: To evaluate the relationship among urolithiasis, metabolic syndrome
(MetS) and serum testosterone (T) level in men. MATERIAL AND METHODS: 513 men
older than 18 years were enrolled in this study: 313 of the subjects had a
history of stones (group 1) and 200 had no history of stones (controls, group 2).
Early morning T levels were recorded and anthropometric measurements were
investigated to evaluate MetS. Analyses were completed using chi-square tests.
RESULT: Serum T level was lower in stone forming patients than control subjects
and 161 (%51.4) men in group 1 and 92 (%46) men in group 2 were diagnosed with
metabolic syndrome. T level was found lower limit (< 285 ng/dl) in the MetS and
urolithiasis group (p 0.002, OR 2.71). CONCLUSIONS: We found low testosterone
levels in the patients with stone disease and prevalence of the MetS in men with
urolithiasis was higher than in men without stone disease. Our findings show that
levels of testosterone had no effect on stone formation, but the factors that
cause stone formation can have an effect on the level of testosterone.
PMID- 25847905
TI - Unusual case of locally advanced and metastatic paratesticular liposarcoma: a
case report and review of the literature.
AB - Liposarcoma accounts for 20% of all sarcomas and is a rare occurrence in the
paratesticular region. We present the case of a 66-year-old man with a massive
liposarcoma of the right scrotum invading the lower limb and the abdominal wall
skin. The case concerns an unusually large and aggressive liposarcoma (25 cm),
presenting with multiple lung and nodal metastases. The patient had an
unfavourable evolution with rapid progression of metastases, although there were
no signs of local disease. In this case, a wide local excision was performed in
order to obtain local control of the disease. Even though paratesticular sarcomas
might have a more favourable evolution, the association with lung involvement
carries an ominous prognosis. Diagnosis of paratesticular sarcoma should be kept
in mind in case of irregular necrotic masses in the inguinal and scrotal region.
PMID- 25847906
TI - An unusual case of intrarenal coiled and ruptured guidewire.
AB - OBJECTIVE: To the best of our knowledge there are only 3 reports of fractured
guidewires inside the pelvicalyceal system, successfully removed with endourology
techniques, and this is the first one presenting a tightly coiled
intraparenchymal section. MATERIAL AND METHODS: A 59-year-old woman was
hospitalized for surgical treatment of a right kidney of reduced size. Past
history revealed pyelolithotomy for a staghorn stone 14 months earlier at another
Institution with subsequent ureteral obstruction, one failed attempt at ureteral
double-J catheter insertion and one failed attempt at percutaneous nephrostomy
placement 5 months postoperatively. Another nephrostomy was placed, but left
indwelling briefly. CT scan demonstrated a small-size kidney with residual stone
fragments and presence of a "device" in the lower pole. The tapered distal
extremity of an hydrophilic guidewire, with a tightly coiled central section
wedged in the renal tissue was found inside the nephrectomy specimen. RESULTS:
While the Radiologist who read the CT scan hypothesized that the "device" was a
fragment of double-J ureteral stent or nephrostomy catheter, it consisted of the
hydrophilic extremity of a guidewire, broken during a previous attempt at
nephrostomy placement. Perirenal fibrosis and inappropriate angle between the
needle and the lower calyx are the likely causes of guidewire coiling during its
advancement and subsequent rupture during withdrawal. CONCLUSIONS: Urologists
must be aware that, although percutaneous nephrostomy has a very high technical
success rate, unusual complications like guidewire fracture may occur, and that
modern imaging techniques can provide an accurate picture of this condition.
PMID- 25847907
TI - Ischemia of the glans penis following circumcision: case report and revision of
the literature.
AB - Ischemic complications of the glans penis are rare and commonly result from
trauma, inadvertent administration of vasoconstrictive solutions, diabetes
mellitus, circumcision and vasculitis; we refer about a young man with severe
ischemia of the glans penis following circumcision. The patient had undergone
circumcision 5 days before in a surgery department under local anesthesia (1%
mepivacaine hydrochloride). The patient noticed a brownish color and edema of the
glans penis at 24 h after he opened the wound dressing, but arrived to our
hospital only 5 days after circumcision because these findings had progressed.
Physical examination revealed the black color or necrotic appearance of the glans
penis, and edema on the dorsal penile skin. The patient underwent antibiotic,
antiplatatelet, corticosteroid and iperbaric therapy achieving a complete
restitutio ad integrum.
PMID- 25847908
TI - Complete intraperitoneal displacement of a double J stent: a first case.
AB - OBJECTIVES: Ureteral double-J stents are known to migrate proximally and distally
within the urinary tract, while perforation and stent displacement are uncommon.
Possible mechanisms of displacement are either original malpositioning with
ureteral perforation or subsequent fistula and erosion of the excretory system,
due to infection or long permanence of the device. We present the unique case of
complete intraperitoneal stent migration in a 59-year-old caucasian male without
evidence of urinary fistula at the moment of diagnosis, so far an unreported
complication. MATERIALS AND METHODS: Eight months after the placement of a double
J stent for lower right ureteral stricture at a district hospital, the patient
came at our observation for urosepsis and hydro-uretero-nephrosis. A CT scan
demonstrated intraperitoneal migration of the stent outside the urinary tract.
Cystoscopy failed to visualize the lower extremity of the stent, a percutaneous
nephrostomy was placed to drain the urinary system and the stent was removed
through a small abdominal incision on the right lower quadrant. RESULTS: In our
case we presume that during the positioning manoeuvre the guide wire perforated
simultaneously the lower ureteral wall and the pelvic peritoneum, and that once
the upper end of the stent was coiled, the lower extremity was also attracted
intraperitoneally. The lack of pain due to the spinal lesion concurred to this
unusual complication. CONCLUSIONS: We must be aware that ureteral double J stents
may be found displaced even inside the peritoneal cavity, and that the use of
retrograde pyelography during placement is of paramount importance to exclude
misplacement of an apparently normally coiled upper extremity of the stent.
PMID- 25847909
TI - A very rare case of adult-type granulosa cell tumor.
AB - Granulosa cell tumor (GST) of the testis is a rare neoplasm. Here we describe a
case of an adult type GST. More than a year after surgical treatment, without any
other treatment, the patient is alive without sign of disease.
PMID- 25847911
TI - Generalized linear mixed models for multi-reader multi-case studies of diagnostic
tests.
AB - Diagnostic tests are often compared in multi-reader multi-case (MRMC) studies in
which a number of cases (subjects with or without the disease in question) are
examined by several readers using all tests to be compared. One of the commonly
used methods for analyzing MRMC data is the Obuchowski-Rockette (OR) method,
which assumes that the true area under the receiver operating characteristic
curve (AUC) for each combination of reader and test follows a linear mixed model
with fixed effects for test and random effects for reader and the reader-test
interaction. This article proposes generalized linear mixed models which
generalize the OR model by incorporating a range-appropriate link function that
constrains the true AUCs to the unit interval. The proposed models can be
estimated by maximizing a pseudo-likelihood based on the approximate normality of
AUC estimates. A Monte Carlo expectation-maximization algorithm can be used to
maximize the pseudo-likelihood, and a non-parametric bootstrap procedure can be
used for inference. The proposed method is evaluated in a simulation study and
applied to an MRMC study of breast cancer detection.
PMID- 25847912
TI - Some comments on "The analysis of multivariate longitudinal data: A review".
AB - We provide a commentary on "The analysis of multivariate longitudinal data: a
review" by Verbeke et al. The authors provide a comprehensive review of the
issues in the analysis of multivariate longitudinal data and use examples to
demonstrate the pros and cons of several approaches. In this commentary, we
indicate some important omissions in their review paper.
PMID- 25847910
TI - Techniques to improve detection and analysis of extracellular vesicles using flow
cytometry.
AB - Extracellular vesicles (EVs) range in size from 50 nm to 1 um. Flow cytometry
(FCM) is the most commonly used method for analyzing EVs; however, accurate
characterization of EVs remains challenging due to their small size and lack of
discrete positive populations. Here we report the use of optimization techniques
that are especially well-suited for analyzing EVs from a high volume of clinical
samples. Utilizing a two pronged approach that included 1) pre-filtration of
antibodies to remove aggregates, followed by 2) detergent lysis of a replicate
sample to account for remaining false positive events, we were able to
effectively limit false positive non-EV events. In addition, we show that lysed
samples are a useful alternative to isotypes for setting gates to exclude
background fluorescence. To reduce background, we developed an approach using
filters to "wash" samples post-staining thus providing a faster alternative to
ultracentrifugation and sucrose gradient fractionation. In conclusion, use of
these optimized techniques enhances the accuracy and efficiency of EV detection
using FCM.
PMID- 25847914
TI - Comprehensive evaluation of poly(I:C) induced inflammatory response in an airway
epithelial model.
AB - Respiratory viruses invade the upper airway of the lung, triggering a potent
immune response that often exacerbates preexisting conditions such as asthma and
COPD. Poly(I:C) is a synthetic analog of viral dsRNA that induces the
characteristic inflammatory response associated with viral infection, such as
loss of epithelial integrity, and increased production of mucus and inflammatory
cytokines. Here, we explore the mechanistic responses to poly(I:C) in a well
defined primary normal human bronchial epithelial (NHBE) model that recapitulates
in vivo functions and responses. We developed functional and quantifiable methods
to evaluate the physiology of our model in both healthy and inflamed states.
Through gene and protein expression, we validated the differentiation state and
population of essential cell subtypes (i.e., ciliated, goblet, club, and basal
cells) as compared to the human lung. Assays for total mucus production, cytokine
secretion, and barrier function were used to evaluate in vitro physiology and
response to viral insult. Cells were treated apically with poly(I:C) and
evaluated 48 h after induction. Results revealed a dose-dependent increase in
goblet cell differentiation, as well as, an increase in mucus production relative
to controls. There was also a dose-dependent increase in secretion of IL-6, IL-8,
TNF-alpha, and RANTES. Epithelial barrier function, as measured by TEER, was
maintained at 1501 +/- 355 Omega*cm2 postdifferentiation, but dropped
significantly when challenged with poly(I:C). This study provides first steps
toward a well-characterized model with defined functional methods for
understanding dsRNA stimulated inflammatory responses in a physiologically
relevant manner.
PMID- 25847915
TI - Reduced fitness and abnormal cardiopulmonary responses to maximal exercise
testing in children and young adults with sickle cell anemia.
AB - Physiologic contributors to reduced exercise capacity in individuals with sickle
cell anemia (SCA) are not well understood. The objective of this study was to
characterize the cardiopulmonary response to maximal cardiopulmonary exercise
testing (CPET) and determine factors associated with reduced exercise capacity
among children and young adults with SCA. A cross-sectional cohort of 60 children
and young adults (mean 15.1 +/- 3.4 years) with hemoglobin SS or S/beta(0)
thalassemia and 30 matched controls (mean 14.6 +/- 3.5 years) without SCA or
sickle cell trait underwent maximal CPET by a graded, symptom-limited cycle
ergometry protocol with breath-by-breath, gas exchange analysis. Compared to
controls without SCA, subjects with SCA demonstrated significantly lower peak VO2
(26.9 +/- 6.9 vs. 37.0 +/- 9.2 mL/kg/min, P < 0.001). Subjects demonstrated
slower oxygen uptake (DeltaVO2/DeltaWR, 9 +/- 2 vs. 12 +/- 2 mL/min/watt, P <
0.001) and lower oxygen pulse (DeltaVO2/DeltaHR, 12 +/- 4 vs. 20 +/- 7 mL/beat, P
< 0.001) as well as reduced oxygen uptake efficiency (DeltaVE/DeltaVO2, 42 +/- 8
vs. 32 +/- 5, P < 0.001) and ventilation efficiency (DeltaVE/DeltaVCO2, 30.3 +/-
3.7 vs. 27.3 +/- 2.5, P < 0.001) during CPET. Peak VO2 remained significantly
lower in subjects with SCA after adjusting for age, sex, body mass index (BMI),
and hemoglobin, which were independent predictors of peak VO2 for subjects with
SCA. In the largest study to date using maximal CPET in SCA, we demonstrate that
children and young adults with SCA have reduced exercise capacity attributable to
factors independent of anemia. Complex derangements in gas exchange and oxygen
uptake during maximal exercise are common in this population.
PMID- 25847916
TI - The influence of sighing respirations on infant lung function measured using
multiple breath washout gas mixing techniques.
AB - There is substantial interest in studying lung function in infants, to better
understand the early life origins of chronic lung diseases such as asthma.
Multiple breath washout (MBW) is a technique for measuring lung function that has
been adapted for use in infants. Respiratory sighs occur frequently in young
infants during natural sleep, and in accordance with current MBW guidelines,
result in exclusion of data from a substantial proportion of testing cycles. We
assessed how sighs during MBW influenced the measurements obtained using data
from 767 tests conducted on 246 infants (50% male; mean age 43 days) as part of a
large cohort study. Sighs occurred in 119 (15%) tests. Sighs during the main part
of the wash-in phase (before the last 5 breaths) were not associated with
differences in standard MBW measurements compared with tests without sighs. In
contrast, sighs that occurred during the washout were associated with a small but
discernible increase in magnitude and variability. For example, the mean lung
clearance index increased by 0.36 (95% CI: 0.11-0.62) and variance increased by a
multiplicative factor of 2 (95% CI: 1.6-2.5). The results suggest it is
reasonable to include MBW data from testing cycles where a sigh occurs during the
wash-in phase, but not during washout, of MBW. By recovering data that would
otherwise have been excluded, we estimate a boost of about 10% to the final
number of acceptable tests and 6% to the number of individuals successfully
tested.
PMID- 25847917
TI - Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier
function and heat shock proteins in intestinal porcine epithelial cells.
AB - Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve
as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic,
Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus
johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on
cytoprotective HSP expression and gut barrier function, were investigated in a
porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells
polarized on a permeable filter exhibited villus-like cell phenotype with
development of apical microvilli. Western blot analysis detected HSP expression
in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to
significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG
did not. For HSP72, only the supernatant of L. reuteri induced the expression,
which was comparable to the heat shock treatment, which indicated that HSP72
expression was more stimulus specific. The protective effect of lactobacilli was
further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC)
challenge. ETEC caused intestinal barrier destruction, as reflected by loss of
cell-cell contact, reduced IPEC-J2 cell viability and transepithelial electrical
resistance, and disruption of tight junction protein zonula occludens-1. In
contrast, the L. reuteri treatment substantially counteracted these detrimental
effects and preserved the barrier function. L. johnsonii and LGG also achieved
barrier protection, partly by directly inhibiting ETEC attachment. Together, the
results indicate that specific strains of Lactobacillus can enhance gut barrier
function through cytoprotective HSP induction and fortify the cell protection
against ETEC challenge through tight junction protein modulation and direct
interaction with pathogens.
PMID- 25847918
TI - Leaky intestine and impaired microbiome in an amyotrophic lateral sclerosis mouse
model.
AB - Emerging evidence has demonstrated that intestinal homeostasis and the microbiome
play essential roles in neurological diseases, such as Parkinson's disease.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
characterized by a progressive loss of motor neurons and muscle atrophy.
Currently, there is no effective treatment. Most patients die within 3-5 years
due to respiratory paralysis. Although the death of motor neurons is a hallmark
of ALS, other organs may also contribute to the disease progression. We examined
the gut of an ALS mouse model, G93A, which expresses mutant superoxide dismutase
(SOD1(G93A)), and discovered a damaged tight junction structure and increased
permeability with a significant reduction in the expression levels of tight
junction protein ZO-1 and the adherens junction protein E-cadherin. Furthermore,
our data demonstrated increased numbers of abnormal Paneth cells in the intestine
of G93A mice. Paneth cells are specialized intestinal epithelial cells that can
sense microbes and secrete antimicrobial peptides, thus playing key roles in host
innate immune responses and shaping the gut microbiome. A decreased level of the
antimicrobial peptides defensin 5 alpha was indeed found in the ALS intestine.
These changes were associated with a shifted profile of the intestinal
microbiome, including reduced levels of Butyrivibrio Fibrisolvens, Escherichia
coli, and Fermicus, in G93A mice. The relative abundance of bacteria was shifted
in G93A mice compared to wild-type mice. Principal coordinate analysis indicated
a difference in fecal microbial communities between ALS and wild-type mice. Taken
together, our study suggests a potential novel role of the intestinal epithelium
and microbiome in the progression of ALS.
PMID- 25847919
TI - Exploring miniaturized EEG electrodes for brain-computer interfaces. An EEG you
do not see?
AB - Electroencephalography (EEG) allows the study of the brain-behavior relationship
in humans. Most of what we have learned with EEG was through observing the brain
behavior relationship under well-controlled laboratory conditions. However, by
reducing "normal" behavior to a minimum the ecological validity of the results
can be limited. Recent developments toward mobile EEG solutions allow to study
the brain-behavior relationship outside the laboratory in more natural
situations. Besides mobility and robustness with respect to motion, mobile EEG
systems should also interfere as little as possible with the participant's
behavior. For example, natural interaction with other people could be hindered
when it is obvious that a participant wears an EEG cap. This study evaluates the
signal quality obtained with an unobtrusive solution for EEG monitoring through
the integration of miniaturized EEG ton-electrodes into both a discreet baseball
cap and an individualized ear piece. We show that such mini electrodes located at
scalp and ear locations can reliably record event related potentials in a P300
brain-computer-interface application.
PMID- 25847920
TI - Lower limb conduit artery endothelial responses to acute upper limb exercise in
spinal cord injured and able-bodied men.
AB - Vascular improvements in the nonactive regions during exercise are likely
primarily mediated by increased shear rate (SR). Individuals with spinal cord
injury (SCI) experience sublesional vascular deconditioning and could potentially
benefit from upper body exercise-induced increases in lower body SR. The present
study utilized a single bout of incremental arm-crank exercise to generate
exercise-induced SR changes in the superficial femoral artery in an effort to
evaluate the acute postexercise impact on superficial femoral artery endothelial
function via flow-mediated dilation (FMD), and determine regulatory factors in
the nonactive legs of individuals with and without SCI. Eight individuals with
SCI and eight age, sex, and waist-circumference-matched able-bodied (AB) controls
participated. Nine minutes of incremental arm-crank exercise increased
superficial femoral artery anterograde SR (P = 0.02 and P < 0.01), retrograde SR
(P < 0.01 and P < 0.01), and oscillatory shear index (OSI) (P < 0.001 and P <
0.001) in both SCI and AB, respectively. However, these SR alterations resulted
in acute postexercise increases in FMD in the AB group only (SCI 6.0 +/- 1.2% to
6.3 +/- 2.7%, P = 0.74; AB 7.5 +/- 1.4% to 11.2 +/- 1.4%, P = 0.03). While arm
exercise has many cardiovascular benefits and results in changes in SR patterns
in the nonactive legs, these changes are not sufficient to induce acute changes
in FMD among individuals with SCI, and therefore are less likely to stimulate
exercise training-associated improvements in nonactive limb endothelial function.
Understanding the role of SR patterns on FMD brings us closer to designing
effective strategies to combat impaired vascular function in both healthy and
clinical populations.
PMID- 25847921
TI - mRNA expression of diacylglycerol kinase isoforms in insulin-sensitive tissues:
effects of obesity and insulin resistance.
AB - Diacylglycerol kinase (DGK) isoforms regulate signal transduction and lipid
metabolism. DGKdelta deficiency leads to hyperglycemia, peripheral insulin
resistance, and metabolic inflexibility. Thus, dysregulation of other DGK
isoforms may play a role in metabolic dysfunction. We investigated DGK isoform
mRNA expression in extensor digitorum longus (EDL) and soleus muscle, liver as
well as subcutaneous and epididymal adipose tissue in C57BL/6J mice and obese and
insulin-resistant ob/ob mice. All DGK isoforms, except for DGKkappa, were
detectable, although with varying mRNA expression. Liver DGK expression was
generally lowest, with several isoforms undetectable. In soleus muscle,
subcutaneous and epididymal adipose tissue, DGKdelta was the most abundant
isoform. In EDL muscle, DGKalpha and DGKzeta were the most abundant isoforms. In
liver, DGKzeta was the most abundant isoform. Comparing obese insulin-resistant
ob/ob mice to lean C57BL/6J mice, DGKbeta, DGKiota, and DGKtheta were increased
and DGKepsilon expression was decreased in EDL muscle, while DGKbeta, DGKeta and
DGKtheta were decreased and DGKdelta and DGKiota were increased in soleus muscle.
In liver, DGKdelta and DGKzeta expression was increased in ob/ob mice. DGKeta was
increased in subcutaneous fat, while DGKzeta was increased and DGKbeta, DGKdelta,
DGKeta and DGKepsilon were decreased in epididymal fat from ob/ob mice. In both
adipose tissue depots, DGKalpha and DGKgamma were decreased and DGKiota was
increased in ob/ob mice. In conclusion, DGK mRNA expression is altered in an
isoform- and tissue-dependent manner in obese insulin-resistant ob/ob mice. DGK
isoforms likely have divergent functional roles in distinct tissues, which may
contribute to metabolic dysfunction.
PMID- 25847922
TI - Time for a level playing field: inequalities in regulatory/approval processes-the
example of bevacizumab in epithelial ovarian cancer.
PMID- 25847923
TI - Problematic Use of Multiple Subgroup Analyses in Assessing the Impact of Aspirin
in Prostate Cancer.
PMID- 25847924
TI - Weighing the options for human epidermal growth factor receptor 2-directed
therapy in metastatic breast cancer.
PMID- 25847926
TI - Adoptive T-cell therapy is a promising salvage approach for advanced or recurrent
metastatic cervical cancer.
PMID- 25847925
TI - Long-term pulmonary function in survivors of childhood cancer.
AB - PURPOSE: This study was undertaken to determine the magnitude of pulmonary
dysfunction in childhood cancer survivors when compared with healthy controls and
the extent (and predictors) of decline over time. PATIENTS AND METHODS: Survivors
underwent baseline (t1) pulmonary function tests, followed by a second
comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3
years). Survivors were also compared with age- and sex-matched healthy controls
at t2. RESULTS: Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9
years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years).
Compared with odds for healthy controls, the odds of restrictive defects were
increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the
odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to
15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0;
95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR,
5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated
with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and
chest radiation dose (referent: no chest radiation; <= 20 Gy: OR, 6.4; 95% CI,
1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were
associated with diffusion abnormalities. Among survivors with normal pulmonary
function tests at t1, females and survivors treated with more than 20 Gy chest
radiation demonstrated decline in diffusion function over time. CONCLUSION:
Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly
more likely to have restrictive and diffusion defects when compared with healthy
controls. Diffusion capacity declines with time after exposure to pulmonary-toxic
therapy, particularly among females and survivors treated with high-dose chest
radiation. These individuals could benefit from subsequent monitoring.
PMID- 25847927
TI - Poison.
PMID- 25847928
TI - Reply to M. Lee et al.
PMID- 25847929
TI - Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy
for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment
of a Tumor-Based Measure of Genomic Instability: PrECOG 0105.
AB - PURPOSE: This study was designed to assess efficacy, safety, and predictors of
response to iniparib in combination with gemcitabine and carboplatin in early
stage triple-negative and BRCA1/2 mutation-associated breast cancer. PATIENTS AND
METHODS: This single-arm phase II study enrolled patients with stage I to IIIA (T
>= 1 cm) estrogen receptor-negative (<= 5%), progesterone receptor-negative (<=
5%), and human epidermal growth factor receptor 2-negative or BRCA1/2 mutation
associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m(2) intravenously
[IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8),
and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21
days for four cycles, until the protocol was amended to six cycles. The primary
end point was pathologic complete response (no invasive carcinoma in breast or
axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous
recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in
pretreatment core breast biopsies. RESULTS: Among 80 patients, median age was 48
years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage
was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete
response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to
46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P
= .02) and remained significant when BRCA1/2 germline mutations carriers were
excluded (P = .021). CONCLUSION: Preoperative combination of gemcitabine,
carboplatin, and iniparib is active in the treatment of early-stage triple
negative and BRCA1/2 mutation-associated breast cancer. The HRD-LOH assay was
able to identify patients with sporadic triple-negative breast cancer lacking a
BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable
pathologic response. Confirmatory controlled trials are warranted.
PMID- 25847930
TI - Outcomes of Patients With Chronic Lymphocytic Leukemia and Richter's
Transformation After Transplantation Failure.
AB - PURPOSE: Allogeneic stem-cell transplantation (SCT) induces long-term remission
in a fraction of patients with high-risk chronic lymphocytic leukemia (CLL) or
Richter's transformation (RT). Our purpose was to determine the outcomes of
patients whose disease progressed after allogeneic SCT. PATIENTS AND METHODS: We
retrospectively analyzed the outcomes of 72 patients (52 with CLL and 20 with RT)
who underwent allogeneic SCT between 1998 and 2011 and had documented progression
after transplantation. Twenty-two (31%) never had a response, and 50 (69%) had a
response but experienced relapse after a median of 7 months (range, 2 to 85
months). Forty-eight patients who were receiving or were candidates to receive
post-SCT cell-based therapies were not included in this analysis. RESULTS: The
median age at time of transplantation was 58 years (range, 30 to 72 years). Sixty
two patients (86%) received more than two treatment regimens and 37 (51%)
received more than three treatment regimens before SCT. Sixty-six patients (92%)
had active disease at the time of transplantation. The 2- and 5-year survival
rates were 67% and 38% (patients with CLL) and 36% and 0% (patients with RT). The
patients who developed acute or chronic graft-versus-host disease had a longer
overall survival (OS; P = .05). In a multivariable analysis, RT or low hemoglobin
at the time of SCT predicted shorter OS. Chronic graft-versus-host disease and an
initial response to SCT predicted longer OS. CONCLUSION: Patients with CLL in
whom allogeneic SCT fails may have a response to and benefit from salvage
therapies, and their prognosis is relatively good.
PMID- 25847931
TI - Molecular profiling is rather likely to be cost effective.
PMID- 25847932
TI - Reply to C.G. Rusthoven et al.
PMID- 25847933
TI - Reply to V.P. Retel et al, D. Gauchan et al, and C. Rahilly-Tierney et al.
PMID- 25847935
TI - Reply to C.G. Rusthoven et al.
PMID- 25847934
TI - SWOG S0925: A Randomized Phase II Study of Androgen Deprivation Combined With
Cixutumumab Versus Androgen Deprivation Alone in Patients With New Metastatic
Hormone-Sensitive Prostate Cancer.
AB - PURPOSE: Cixutumumab, formerly IMC-A12, is a recombinant human monoclonal
immunoglobulin G1 antibody that targets insulin-like growth factor I receptor
(IGF-IR). Cixutumumab was synergistic with castration in a hormone-sensitive
prostate cancer xenograft model. PATIENTS AND METHODS: Patients with new
metastatic prostate cancer were randomly assigned within 30 days of initiating
androgen deprivation (AD) to cixutumumab added to a luteinizing hormone-releasing
hormone agonist with bicalutamide versus AD alone. With 180 patients and one
sided alpha of 0.10, there would be 90% power to detect an absolute 20%
difference in undetectable prostate-specific antigen (PSA; <= 0.2 ng/mL) rate at
28 weeks (relative risk, 1.44); this end point was previously strongly correlated
with survival. Secondary end points included the proportion of patients with PSA
> 4.0 ng/mL, safety and tolerability, circulating tumor cell (CTC) levels, and
seven plasma IGF-IR biomarkers. Fisher's exact test was used for the primary end
point, and extended Mantel-Haenszel chi(2) test was used for three PSA response
categories. RESULTS: The trial accrued 210 eligible patients (105 randomly
assigned to each arm). Patient characteristics were similar in both arms.
Undetectable PSA rate was 42 (40.0%) of 105 for cixutumumab plus AD and 34
(32.3%) of 105 for AD alone (relative risk, 1.24; one-sided P = .16). Lower
baseline CTCs (0 v 1 to 4 v >= 5/7.5 mL whole blood) were associated with higher
rate of PSA response (three categories; P = .036) in 39 evaluable patients. IGF
IR biomarkers were not correlated with PSA outcome, and cixutumumab did not
significantly change these biomarker levels. CONCLUSION: Cixutumumab plus AD did
not significantly increase the undetectable PSA rate in men with new metastatic
hormone-sensitive prostate cancer. CTCs at baseline may carry prognostic value.
PMID- 25847937
TI - External Validation of the Benefit of Adjuvant Radiotherapy for Pathologic N1M0
Prostate Cancer.
PMID- 25847936
TI - TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With
Biomarker Assessment in Metastatic Triple-Negative Breast Cancer.
AB - PURPOSE: The identification of patients with metastatic triple-negative breast
cancer (mTNBC) who are expected to benefit from platinum-based chemotherapy is of
interest. We conducted a single-arm phase II clinical trial of single-agent
platinum for mTNBC with biomarker correlates. PATIENTS AND METHODS: Patients with
mTNBC received first- or second-line cisplatin (75 mg/m(2)) or carboplatin (area
under the concentration-time curve 6) by physician's choice once every 3 weeks.
Coprimary end points were objective response rate (RR) and response prediction by
p63/p73 gene expression. Secondary and exploratory end points included toxicity
assessment, RR in cisplatin versus carboplatin, and RR in molecularly defined
subgroups, including BRCA1/2 mutation carriers. RESULTS: Patients (N = 86; 69 as
first-line therapy) received cisplatin (n = 43) or carboplatin (n = 43). RR was
25.6% (95% CI, 16.8% to 36%) and was numerically higher with cisplatin (32.6%)
than with carboplatin (18.7%). RR was 54.5% in patients with germline BRCA1/2
mutations (n = 11). In patients without BRCA1/2 mutations (n = 66), exploratory
analyses showed that a BRCA-like genomic instability signature (n = 32)
discriminated responding and nonresponding tumors (mean homologous recombination
deficiency-loss of heterozygosity/homologous recombination deficiency-large-scale
state transitions [HRD-LOH/HRD-LST] scores were 12.68 and 5.11, respectively),
whereas predefined analysis by p63/p73 expression status (n = 61), p53 and PIK3CA
mutation status (n = 53), or PAM50 gene expression subtype (n = 55) did not. Five
of the six long-term responders alive at a median of 4.5 years lacked germline
BRCA1/2 mutations, and two of them had increased tumor HRD-LOH/HRD-LST scores.
CONCLUSION: Platinum agents are active in mTNBC, especially in patients with
germline BRCA1/2 mutations. A measure of tumor DNA repair function may identify
patients without mutations who could benefit from platinum therapy agents.
Prospective controlled confirmatory trials are warranted.
PMID- 25847938
TI - Cost-effectiveness of the 70-gene signature versus adjuvant! Online and
systematic chemotherapy for risk stratification of patients with node-negative
breast cancer: does accuracy matter?
PMID- 25847939
TI - Cost-effectiveness of molecular profiling for early breast cancer.
PMID- 25847940
TI - Concerns about cancer risk and experiences with genetic testing in a diverse
population of patients with breast cancer.
AB - PURPOSE: To evaluate preferences for and experiences with genetic testing in a
diverse cohort of patients with breast cancer identified through population-based
registries, with attention to differences by race/ethnicity. METHODS: We surveyed
women diagnosed with nonmetastatic breast cancer from 2005 to 2007, as reported
to the SEER registries of metropolitan Los Angeles and Detroit, about experiences
with hereditary risk evaluation. Multivariable models evaluated correlates of a
strong desire for genetic testing, unmet need for discussion with a health care
professional, and receipt of testing. RESULTS: Among 1,536 patients who completed
the survey, 35% expressed strong desire for genetic testing, 28% reported
discussing testing with a health care professional, and 19% reported test
receipt. Strong desire for testing was more common in younger women, Latinas, and
those with family history. Minority patients were significantly more likely to
have unmet need for discussion (failure to discuss genetic testing with a health
professional when they had a strong desire for testing): odds ratios of 1.68,
2.44, and 7.39 for blacks, English-speaking Latinas, and Spanish-speaking Latinas
compared with whites, respectively. Worry in the long-term survivorship period
was higher among those with unmet need for discussion (48.7% v 24.9%; P <.001).
Patients who received genetic testing were younger, less likely to be black, and
more likely to have a family cancer history. CONCLUSION: Many patients,
especially minorities, express a strong desire for genetic testing and may
benefit from discussion to clarify risks. Clinicians should discuss genetic risk
even with patients they perceive to be at low risk, as this may reduce worry.
PMID- 25847941
TI - EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab
Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer.
AB - PURPOSE: Glycoprotein NMB (gpNMB), a negative prognostic marker, is overexpressed
in multiple tumor types. Glembatumumab vedotin is a gpNMB-specific monoclonal
antibody conjugated to the potent cytotoxin monomethyl auristatin E. This phase
II study investigated the activity of glembatumumab vedotin in advanced breast
cancer by gpNMB expression. PATIENTS AND METHODS: Patients (n = 124) with
refractory breast cancer that expressed gpNMB in >= 5% of epithelial or stromal
cells by central immunohistochemistry were stratified by gpNMB expression (tumor,
low stromal intensity, high stromal intensity) and were randomly assigned 2:1 to
glembatumumab vedotin (n = 83) or investigator's choice (IC) chemotherapy (n =
41). The study was powered to detect overall objective response rate (ORR) in the
glembatumumab vedotin arm between 10% (null) and 22.5% (alternative hypothesis)
with preplanned investigation of activity by gpNMB distribution and/or intensity
(Stratum 1 to Stratum 3). RESULTS: Glembatumumab vedotin was well tolerated as
compared with IC chemotherapy (less hematologic toxicity; more rash, pruritus,
neuropathy, and alopecia). ORR was 6% (five of 83) for glembatumumab vedotin
versus 7% (three of 41) for IC, without significant intertreatment differences
for predefined strata. Secondary end point revealed ORR of 12% (10 of 83) versus
12% (five of 41) overall, and 30% (seven of 23) versus 9% (one of 11) for gpNMB
overexpression (>= 25% of tumor cells). Unplanned analysis showed ORR of 18%
(five of 28) versus 0% (0 of 11) in patients with triple-negative breast cancer
(TNBC), and 40% (four of 10) versus 0% (zero of six) in gpNMB-overexpressing
TNBC. CONCLUSION: Glembatumumab vedotin is well tolerated in heavily pretreated
patients with breast cancer. Although the primary end point in advanced gpNMB
expressing breast cancer was not met for all enrolled patients (median tumor
gpNMB expression, 5%), activity may be enhanced in patients with gpNMB
overexpressing tumors and/or TNBC. A pivotal phase II trial (METRIC [Metastatic
Triple-Negative Breast Cancer]) is underway.
PMID- 25847945
TI - Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial
cells blunts inflammatory signaling.
AB - JAK-STAT signaling mediates the actions of numerous cytokines and growth factors,
and its endogenous brake is the family of SOCS proteins. Consistent with their
intracellular roles, SOCS proteins have never been identified in the
extracellular space. Here we report that alveolar macrophages can secrete SOCS1
and -3 in exosomes and microparticles, respectively, for uptake by alveolar
epithelial cells and subsequent inhibition of STAT activation. Secretion is
tunable and occurs both in vitro and in vivo. SOCS secretion into lung lining
fluid was diminished by cigarette smoking in humans and mice. Secretion and
transcellular delivery of vesicular SOCS proteins thus represent a new model for
the control of inflammatory signaling, which is subject to dysregulation during
states of inflammation.
PMID- 25847946
TI - An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene
expression during thymocyte development.
AB - Rag1 and Rag2 gene expression in CD4(+)CD8(+) double-positive (DP) thymocytes
depends on the activity of a distant anti-silencer element (ASE) that counteracts
the activity of an intergenic silencer. However, the mechanistic basis for ASE
activity is unknown. Here, we show that the ASE physically interacts with the
distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters
together to form an active chromatin hub. Moreover, we show that the ASE
functions as a classical enhancer that can potently activate these promoters in
the absence of the silencer or other locus elements. In thymocytes lacking the
chromatin organizer SATB1, we identified a partial defect in Tcra gene
rearrangement that was associated with reduced expression of Rag1 and Rag2 at the
DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of
Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1
and Rag2 promoters. Our results provide a novel framework for understanding ASE
function and demonstrate a novel role for SATB1 as a regulator of Rag locus
organization and gene expression in DP thymocytes.
PMID- 25847947
TI - DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and
tumor cell survival in diffuse large B cell lymphoma.
AB - The epigenetic dysregulation of tumor suppressor genes is an important driver of
human carcinogenesis. We have combined genome-wide DNA methylation analyses and
gene expression profiling after pharmacological DNA demethylation with functional
screening to identify novel tumor suppressors in diffuse large B cell lymphoma
(DLBCL). We find that a CpG island in the promoter of the dual-specificity
phosphatase DUSP4 is aberrantly methylated in nodal and extranodal DLBCL,
irrespective of ABC or GCB subtype, resulting in loss of DUSP4 expression in 75%
of >200 examined cases. The DUSP4 genomic locus is further deleted in up to 13%
of aggressive B cell lymphomas, and the lack of DUSP4 is a negative prognostic
factor in three independent cohorts of DLBCL patients. Ectopic expression of wild
type DUSP4, but not of a phosphatase-deficient mutant, dephosphorylates c-JUN N
terminal kinase (JNK) and induces apoptosis in DLBCL cells. Pharmacological or
dominant-negative JNK inhibition restricts DLBCL survival in vitro and in vivo
and synergizes strongly with the Bruton's tyrosine kinase inhibitor ibrutinib.
Our results indicate that DLBCL cells depend on JNK signaling for survival. This
finding provides a mechanistic basis for the clinical development of JNK
inhibitors in DLBCL, ideally in synthetic lethal combinations with inhibitors of
chronic active B cell receptor signaling.
PMID- 25847948
TI - Hypoxia-independent upregulation of placental hypoxia inducible factor-1alpha
gene expression contributes to the pathogenesis of preeclampsia.
AB - Accumulation of hypoxia inducible factor-1alpha (HIF-1alpha) is commonly an acute
and beneficial response to hypoxia, whereas chronically elevated HIF-1alpha is
associated with multiple disease conditions, including preeclampsia, a serious
hypertensive disease of pregnancy. However, the molecular basis underlying the
persistent elevation of placental HIF-1alpha in preeclampsia and its role in the
pathogenesis of preeclampsia are poorly understood. Here we report that Hif
1alpha mRNA and HIF-1alpha protein were elevated in the placentas of pregnant
mice infused with angiotensin II type I receptor agonistic autoantibody, a
pathogenic factor in preeclampsia. Knockdown of placental Hif-1alpha mRNA by
specific siRNA significantly attenuated hallmark features of preeclampsia induced
by angiotensin II type I receptor agonistic autoantibody in pregnant mice,
including hypertension, proteinuria, kidney damage, impaired placental
vasculature, and elevated maternal circulating soluble fms-like tyrosine kinase-1
levels. Next, we discovered that Hif-1alpha mRNA levels and HIF-1alpha protein
levels were induced in an independent preeclampsia model with infusion of the
inflammatory cytokine tumor necrosis factor superfamily member 14 (LIGHT). SiRNA
knockdown experiments also demonstrated that elevated HIF-1alpha contributed to
LIGHT-induced preeclampsia features. Translational studies with human placentas
showed that angiotensin II type I receptor agonistic autoantibody or LIGHT is
capable of inducing HIF-1alpha in a hypoxia-independent manner. Moreover,
increased HIF-1alpha was found to be responsible for angiotensin II type I
receptor agonistic autoantibody or LIGHT-induced elevation of Flt-1 gene
expression and production of soluble fms-like tyrosine kinase-1 in human villous
explants. Overall, we demonstrated that hypoxia-independent stimulation of HIF
1alpha gene expression in the placenta is a common pathogenic mechanism promoting
disease progression. Our findings reveal new insight to preeclampsia and
highlight novel therapeutic possibilities for the disease.
PMID- 25847949
TI - Regulatory T cells ameliorate intrauterine growth retardation in a transgenic rat
model for preeclampsia.
AB - Preeclampsia is a multisystemic syndrome during pregnancy that is often
associated with intrauterine growth retardation. Immunologic dysregulation,
involving T cells, is implicated in the pathogenesis. The aim of this study was
to evaluate the effect of upregulating regulatory T cells in an established
transgenic rat model for preeclampsia. Application of superagonistic monoclonal
antibody for CD28 has been shown to effectively upregulate regulatory T cells. In
the first protocol (treatment protocol), we applied 1 mg of CD28 superagonist or
control antibody on days 11 and 15 of pregnancy. In the second protocol
(prevention protocol), the superagonist or control antibody was applied on days
1, 5, and 9. Superagonist increased regulatory T cells in circulation and
placenta from 8.49+/-2.09% of CD4-positive T cells to 23.50+/-3.05% and from
3.85+/-1.45% to 23.27+/-7.64%, respectively. Blood pressure and albuminuria
(30.6+/-15.1 versus 14.6+/-5.5 mg/d) were similar in the superagonist or control
antibody-treated preeclamptic group for both protocols. Rats treated with CD28
superagonist showed increased pup weights in the prevention protocol (2.66+/-0.03
versus 2.37+/-0.05 g) and in the treatment protocol (3.04+/-0.04 versus 2.54+/
0.1 g). Intrauterine growth retardation, calculated by brain:liver weight ratio,
was also decreased by the superagonist in both protocols. Further analysis of
brain development revealed a 20% increase in brain volume by the superagonist.
Induction of regulatory T cells in the circulation and the uteroplacental unit in
an established preeclamptic rat model had no influence on maternal hypertension
and proteinuria. However, it substantially improved fetal outcome by ameliorating
intrauterine growth retardation.
PMID- 25847950
TI - Incident atrial fibrillation hazard in hypertensive population: a risk function
from and for clinical practice.
AB - Determining the risk of atrial fibrillation within the hypertensive population
without ischemic vascular disease would aid in decision making on preventive
approaches. Accordingly, we aimed to estimate the risk of incident atrial
fibrillation in this population. We conducted an historical cohort study between
July 1, 2006, and December 31, 2011, using anonymized longitudinal patient
information from primary care and hospital discharge records contained in the
System for the Development of Research in Primary Care database. We included 255
440 hypertensive patients, aged >=55 years at the time of study entry.
Individuals with previous atrial fibrillation, ischemic heart disease, stroke,
and peripheral artery disease were excluded. To build the incident atrial
fibrillation risk function, a derivation and a validation cohort were defined,
representing 60% and 40% of the entire database, respectively, and a Cox
proportional hazards model was fitted. Atrial fibrillation incidence was 7.24 per
1000 person-years (95% confidence interval, 7.08-7.40). The final model included
age, weight, total cholesterol, heart failure, valvular heart disease, and
antihypertensive treatment. Its concordance index (standard error) was 0.769
(0.004) and 0.768 (0.005) in the derivation and validation datasets,
respectively. This research provides a tool, built with variables from daily
clinical practice, that can be readily used in the primary care setting to
predict atrial fibrillation incidence in the hypertensive population without
ischemic vascular disease. The tool may help tailor individualized diagnostic and
preventive care decisions.
PMID- 25847954
TI - Old Habits Die Hard: Addiction of BRAF-Mutant Cancer Cells to MAP Kinase
Signaling.
AB - Dual and triple combination therapies with RAF inhibitors plus other targeted
agents have demonstrated promising clinical utility in BRAFV600-mutant solid
tumors. However, despite vertical inhibition at multiple nodes on the MAPK
signaling pathway, resistant tumors emerge. Ahronian and colleagues show that in
BRAF-mutant colorectal cancer, resistance involves reactivation of
RAS/RAF/MEK/ERK signaling and may be overcome by newly emerging ERK inhibitors.
PMID- 25847955
TI - miRSNP-Based Approach Identifies a miRNA That Regulates Prostate-Specific Antigen
in an Allele-Specific Manner.
AB - A recent study identified genetic variations within the miRNA response elements
of miRNA target genes (miRSNP) that can affect the base paring between miRNAs and
their targets, and hence alter miRNA-target interactions. The authors also
undertook functional validation studies and were able to demonstrate that
overexpression of miR-3162-5p resulted in a 20% decrease in expression of the
KLK3 rs1058205 SNP T-allele.
PMID- 25847956
TI - Targeting Autophagy in BRAF-Mutant Tumors.
AB - Recent studies have highlighted the opportunity to treat cancer by inhibiting
autophagy, but have also raised important caveats with this idea. An article in
this issue of Cancer Discovery adds to accumulating evidence suggesting that we
should focus our efforts (at least initially) on specific tumors where we are
most likely to see beneficial effects.
PMID- 25847957
TI - Paralog-Specific Kinase Inhibition of FGFR4: Adding to the Arsenal of Anti-FGFR
Agents.
AB - In this issue of Cancer Discovery, Hagel and colleagues report the design and the
in vitro and in vivo activity of a novel, irreversible, paralog-specific kinase
inhibitor of FGFR4, BLU9931. This compound binds covalently to a cysteine residue
in the hinge region of FGFR4 but not in FGFR1-3. BLU9931 induces tumor shrinkage
in hepatocellular carcinoma models that express a functioning ligand/receptor
complex consisting of FGF19/FGFR4/KLB and adds to a growing list of anti-FGFR4
agents.
PMID- 25847958
TI - Selective requirement of the shikimate pathway of Legionella pneumophila for
intravacuolar growth within human macrophages but not within Acanthamoeba.
AB - Legionella pneumophila utilizes the Dot/Icm type IV translocation system to
proliferate within a vacuole in a wide variety of natural amoebal hosts and in
alveolar macrophages of the human accidental host. Although L. pneumophila
utilizes host amino acids as the main sources of carbon and energy, it is not
known whether de novo synthesis of amino acids by intravacuolar L. pneumophila
contributes to its nutrition. The aroB and aroE genes encode enzymes for the
shikimate pathway that generates the aromatic amino acids Phe, Trp, and Tyr. Here
we show the aroB and aroE mutants of L. pneumophila to be defective in growth in
human monocyte-derived macrophages (hMDMs) but not in Acanthamoeba spp. The aroB
and aroE mutants are severely attenuated in intrapulmonary proliferation in the
A/J mouse model of Legionnaires' disease, and the defect is fully complemented by
the respective wild-type alleles. The two mutants grow normally in rich media but
do not grow in defined media lacking aromatic amino acids, and the growth defect
is rescued by inclusion of the aromatic amino acids, which are essential for
production of the pyomelanin pigment. Interestingly, supplementation of infected
hMDMs with the three aromatic amino acids or with Trp alone rescues the
intramacrophage defect of the aroE but not the aroB mutant. Therefore, the
shikimate pathway of L. pneumophila is differentially required for optimal growth
within human macrophages, which are auxotrophic for Trp and Phe, but is
dispensable for growth within the Acanthamoeba spp. that synthesize the aromatic
amino acids.
PMID- 25847960
TI - Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal
explants.
AB - We developed a porcine dermal explant model to determine the extent to which
Staphylococcus aureus biofilm communities deplete oxygen, change pH, and produce
damage in underlying tissue. Microelectrode measurements demonstrated that
dissolved oxygen (DO) in biofilm-free dermal tissue was 4.45 +/- 1.17 mg/liter,
while DO levels for biofilm-infected tissue declined sharply from the surface,
with no measurable oxygen detectable in the underlying dermal tissue. Magnetic
resonance imaging demonstrated that biofilm-free dermal tissue had a
significantly lower relative effective diffusion coefficient (0.26 +/- 0.09 to
0.30 +/- 0.12) than biofilm-infected dermal tissue (0.40 +/- 0.12 to 0.48 +/-
0.12; P < 0.0001). Thus, the difference in DO level was attributable to biofilm
induced oxygen demand rather than changes in oxygen diffusivity. Microelectrode
measures showed that pH within biofilm-infected explants was more alkaline than
in biofilm-free explants (8.0 +/- 0.17 versus 7.5 +/- 0.15, respectively; P <
0.002). Cellular and nuclear details were lost in the infected explants,
consistent with cell death. Quantitative label-free shotgun proteomics
demonstrated that both proapoptotic programmed cell death protein 5 and
antiapoptotic macrophage migration inhibitory factor accumulated in the infected
explant spent medium, compared with uninfected-explant spent media (1,351-fold
and 58-fold, respectively), consistent with the cooccurrence of apoptosis and
necrosis in the explants. Biofilm-origin proteins reflected an extracellular
matrix-adapted lifestyle of S. aureus. S. aureus biofilms deplete oxygen,
increase pH, and induce cell death, all factors that contribute to impede wound
healing.
PMID- 25847959
TI - Mechanisms of inflammasome activation by Vibrio cholerae secreted toxins vary
with strain biotype.
AB - Activation of inflammasomes is an important aspect of innate immune responses to
bacterial infection. Recent studies have linked Vibrio cholerae secreted toxins
to inflammasome activation by using murine macrophages. To increase relevance to
human infection, studies of inflammasome-dependent cytokine secretion were
conducted with the human THP-1 monocytic cell line and corroborated in primary
human peripheral blood mononuclear cells (PBMCs). Both El Tor and classical
strains of V. cholerae activated ASC (apoptosis-associated speck-like protein
containing a CARD domain)-dependent release of interleukin-1beta (IL-1beta) when
cultured with human THP-1 cells, but the pattern of induction was distinct,
depending on the repertoire of toxins the strains produced. El Tor biotype
strains induced release of IL-1beta dependent on NOD-like receptor family pyrin
domain-containing 3 (NLRP3) and ASC due to the secreted pore-forming toxin
hemolysin. Unlike in studies with mouse macrophages, the MARTX toxin did not
contribute to IL-1beta release from human monocytic cells. Classical biotype
strains, which do not produce either hemolysin or the MARTX toxin, activated low
level IL-1beta release that was induced by cholera toxin (CT) and dependent on
ASC but independent of NLRP3 and pyroptosis. El Tor strains likewise showed
increased IL-1beta production dependent on CT when the hemolysin gene was
deleted. In contrast to studies with murine macrophages, this phenotype was
dependent on a catalytically active CT A subunit capable of inducing production
of cyclic AMP and not on the B subunit. These studies demonstrate that the
induction of the inflammasome in human THP-1 monocytes and in PBMCs by V.
cholerae varies with the biotype and is mediated by both NLRP3-dependent and
independent pathways.
PMID- 25847961
TI - Transcriptional analysis of the MrpJ network: modulation of diverse virulence
associated genes and direct regulation of mrp fimbrial and flhDC flagellar
operons in Proteus mirabilis.
AB - The enteric bacterium Proteus mirabilis is associated with a significant number
of catheter-associated urinary tract infections (UTIs). Strict regulation of the
antagonistic processes of adhesion and motility, mediated by fimbriae and
flagella, respectively, is essential for disease progression. Previously, the
transcriptional regulator MrpJ, which is encoded by the mrp fimbrial operon, has
been shown to repress both swimming and swarming motility. Here we show that MrpJ
affects an array of cellular processes beyond adherence and motility. Microarray
analysis found that expression of mrpJ mimicking levels observed during UTIs
leads to differential expression of 217 genes related to, among other functions,
bacterial virulence, type VI secretion, and metabolism. We probed the molecular
mechanism of transcriptional regulation by MrpJ using transcriptional reporters
and chromatin immunoprecipitation (ChIP). Binding of MrpJ to two virulence
associated target gene promoters, the promoters of the flagellar master regulator
flhDC and mrp itself, appears to be affected by the condensation state of the
native chromosome, although both targets share a direct MrpJ binding site
proximal to the transcriptional start. Furthermore, an mrpJ deletion mutant
colonized the bladders of mice at significantly lower levels in a transurethral
model of infection. Additionally, we observed that mrpJ is widely conserved in a
collection of recent clinical isolates. Altogether, these findings support a role
of MrpJ as a global regulator of P. mirabilis virulence.
PMID- 25847962
TI - Inactivation of the antifungal and immunomodulatory properties of human
cathelicidin LL-37 by aspartic proteases produced by the pathogenic yeast Candida
albicans.
AB - Constant cross talk between Candida albicans yeast cells and their human host
determines the outcome of fungal colonization and, eventually, the progress of
infectious disease (candidiasis). An effective weapon used by C. albicans to cope
with the host defense system is the release of 10 distinct secreted aspartic
proteases (SAPs). Here, we validate a hypothesis that neutrophils and epithelial
cells use the antimicrobial peptide LL-37 to inactivate C. albicans at sites of
candidal infection and that C. albicans uses SAPs to effectively degrade LL-37.
LL-37 is cleaved into multiple products by SAP1 to -4, SAP8, and SAP9, and this
proteolytic processing is correlated with the gradual decrease in the antifungal
activity of LL-37. Moreover, a major intermediate of LL-37 cleavage-the LL-25
peptide-is antifungal but devoid of the immunomodulatory properties of LL-37. In
contrast to LL-37, LL-25 did not affect the generation of reactive oxygen species
by neutrophils upon treatment with phorbol esters. Stimulating neutrophils with
LL-25 (rather than LL-37) significantly decreased calcium flux and interleukin-8
production, resulting in lower chemotactic activity of the peptide against
neutrophils, which may decrease the recruitment of neutrophils to infection foci.
LL-25 also lost the function of LL-37 as an inhibitor of neutrophil apoptosis,
thereby reducing the life span of these defense cells. This study indicates that
C. albicans can effectively use aspartic proteases to destroy the antimicrobial
and immunomodulatory properties of LL-37, thus enabling the pathogen to survive
and propagate.
PMID- 25847963
TI - Air pollution particulate matter alters antimycobacterial respiratory epithelium
innate immunity.
AB - Inhalation exposure to indoor air pollutants and cigarette smoke increases the
risk of developing tuberculosis (TB). Whether exposure to ambient air pollution
particulate matter (PM) alters protective human host immune responses against
Mycobacterium tuberculosis has been little studied. Here, we examined the effect
of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters
below 2.5 MUm (PM2.5) and 10 MUm (PM10) on innate antimycobacterial immune
responses in human alveolar type II epithelial cells of the A549 cell line.
Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express
the antimicrobial peptides human beta-defensin 2 (HBD-2) and HBD-3 upon infection
with M. tuberculosis and increased intracellular M. tuberculosis growth (as
measured by CFU count). The observed modulation of antibacterial responsiveness
by PM exposure was associated with the induction of senescence in PM-exposed A549
cells and was unrelated to PM-mediated loss of cell viability. Thus, the
induction of senescence and downregulation of HBD-2 and HBD-3 expression in
respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis
growth represent mechanisms by which exposure to air pollution PM may increase
the risk of M. tuberculosis infection and the development of TB.
PMID- 25847964
TI - AMA1-deficient Toxoplasma gondii parasites transiently colonize mice and trigger
an innate immune response that leads to long-lasting protective immunity.
AB - The apical membrane antigen 1 (AMA1) protein was believed to be essential for the
perpetuation of two Apicomplexa parasite genera, Plasmodium and Toxoplasma, until
we genetically engineered viable parasites lacking AMA1. The reduction in
invasiveness of the Toxoplasma gondii RH-AMA1 knockout (RH-AMA1(KO)) tachyzoite
population, in vitro, raised key questions about the outcome associated with
these tachyzoites once inoculated in the peritoneal cavity of mice. In this
study, we used AMNIS technology to simultaneously quantify and image the
parasitic process driven by AMA1(KO) tachyzoites. We report their ability to
colonize and multiply in mesothelial cells and in both resident and recruited
leukocytes. While the RH-AMA1(KO) population amplification is rapidly lethal in
immunocompromised mice, it is controlled in immunocompetent hosts, where immune
cells in combination sense parasites and secrete proinflammatory cytokines. This
innate response further leads to a long-lasting status immunoprotective against a
secondary challenge by high inocula of the homologous type I or a distinct type
II T. gondii genotypes. While AMA1 is definitively not an essential protein for
tachyzoite entry and multiplication in host cells, it clearly assists the
expansion of parasite population in vivo.
PMID- 25847965
TI - Pneumoperitoneum as a valuable option in the treatment of post lower lobectomy
bronchopleural fistula.
AB - Although the incidence of post-lobectomy bronchopleural fistula has decreased
over years, it remains a threatening complication in lung surgery. Once the
fistula is diagnosed, treatment options are several. Conservative versus
operative treatment is currently a matter of debate generally regarding timing,
patient's condition and fistula's size. Although prompt resurgery is strongly
suggested for early onset large fistulas, the clinical scenario may suggest a
cautious conduct and conservative treatment could be advocated and repeated.
Endoscopic management is now widely employed for limited, small bronchial
dehiscence while pneumoperitoneum has surprisingly never been reported for this
purpose, despite its potential. We report a case of a complete right lower lobe
bronchial stump reopening, successfully treated by pneumoperitoneum.
PMID- 25847966
TI - Development of an algorithm to plan and simulate a new interventional procedure.
AB - OBJECTIVES: The number of implanted biological valves for treatment of valvular
heart disease is growing and a percentage of these patients will eventually
undergo a transcatheter valve-in-valve (ViV) procedure. Some of these patients
will represent challenging cases. The aim of this study was to develop a feasible
algorithm to plan and in vitro simulate a new interventional procedure to improve
patient outcome. METHODS: In addition to standard diagnostic routine, our
algorithm includes 3D printing of the annulus, hydrodynamic measurements and high
speed analysis of leaflet kinematics after simulation of the procedure in
different prosthesis positions as well as X-ray imaging of the most suitable
valve position to create a 'blueprint' for the patient procedure. RESULTS: This
algorithm was developed for a patient with a degenerated Perceval aortic
sutureless prosthesis requiring a ViV procedure. Different ViV procedures were
assessed in the algorithm and based on these results the best option for the
patient was chosen. The actual procedure went exactly as planned with help of
this algorithm. CONCLUSIONS: Here we have developed a new technically feasible
algorithm simulating important aspects of a novel interventional procedure prior
to the actual procedure. This algorithm can be applied to virtually all patients
requiring a novel interventional procedure to help identify risks and find
optimal parameters for prosthesis selection and placement in order to maximize
safety for the patient.
PMID- 25847969
TI - A Sensory 3D Map of the Odor Description Space Derived from a Comparison of
Numeric Odor Profile Databases.
AB - Many authors have proposed different schemes of odor classification, which are
useful to aid the complex task of describing smells. However, reaching a
consensus on a particular classification seems difficult because our
psychophysical space of odor description is a continuum and is not clustered into
well-defined categories. An alternative approach is to describe the perceptual
space of odors as a low-dimensional coordinate system. This idea was first
proposed by Crocker and Henderson in 1927, who suggested using numeric profiles
based on 4 dimensions: "fragrant," "acid," "burnt," and "caprylic." In the
present work, the odor profiles of 144 aroma chemicals were compared by means of
statistical regression with comparable numeric odor profiles obtained from 2
databases, enabling a plausible interpretation of the 4 dimensions. Based on the
results and taking into account comparable 2D sensory maps of odor descriptors
from the literature, a 3D sensory map (odor cube) has been drawn up to improve
understanding of the similarities and dissimilarities of the odor descriptors
most frequently used in fragrance chemistry.
PMID- 25847967
TI - alphabeta TCR-mediated recognition: relevance to tumor-antigen discovery and
cancer immunotherapy.
AB - alphabeta T lymphocytes sense perturbations in host cellular body components
induced by infectious pathogens, oncogenic transformation, or chemical or
physical damage. Millions to billions of these lymphocytes are generated through
T-lineage development in the thymus, each endowed with a clonally restricted
surface T-cell receptor (TCR). An individual TCR has the capacity to recognize a
distinct "foreign" peptide among the myriad of antigens that the mammalian host
must be capable of detecting. TCRs explicitly distinguish foreign from self
peptides bound to major histocompatibility complex (MHC) molecules. This is a
daunting challenge, given that the MHC-linked peptidome consists of thousands of
distinct peptides with a relevant nonself target antigen often embedded at low
number, among orders of magnitude higher frequency self-peptides. In this Masters
of Immunology article, I review how TCR structure and attendant mechanobiology
involving nonlinear responses affect sensitivity as well as specificity to meet
this requirement. Assessment of human tumor-cell display using state-of-the-art
mass spectrometry physical detection methods that quantify epitope copy number
can help to provide information about requisite T-cell functional avidity
affording protection and/or therapeutic immunity. Future rational CD8 cytotoxic T
cell-based vaccines may follow, targeting virally induced cancers, other nonviral
immunogenic tumors, and potentially even nonimmunogenic tumors whose peptide
display can be purposely altered by MHC-binding drugs to stimulate immune attack.
PMID- 25847968
TI - The emerging understanding of myeloid cells as partners and targets in tumor
rejection.
AB - Myeloid cells are the most prominent among cells capable of presenting tumor
derived antigens to T cells and thereby maintaining the latter in an activated
state. Myeloid populations of the tumor microenvironment prominently include
monocytes and neutrophils (sometimes loosely grouped as myeloid-derived
suppressor cells), macrophages, and dendritic cells. Although intratumoral
myeloid populations, as a whole, have long been considered nonstimulatory or
suppressive, it has only recently been appreciated that not all tumor
infiltrating myeloid cells are made equal. Because of advances in high
dimensional flow cytometry as well as more robust transcriptional profiling, we
now also understand that the subsets of the tumor-myeloid compartment are far
more diverse and notably even contain a rare population of stimulatory dendritic
cells. As all of these myeloid populations represent major T-cell-interacting
partners for incoming tumor-reactive cytotoxic T lymphocytes, understanding the
distinctions in their lineage and function reveals and guides numerous
therapeutic avenues targeting these antigen-presenting cells. In this Cancer
Immunology at the Crossroads overview, we review the recent progress in this
rapidly evolving field and advance the hypothesis that the antigen-presenting
compartment within tumor microenvironments may contain significant numbers of
potent allies to be leveraged for immune-based tumor clearance.
PMID- 25847970
TI - Monocyte phenotypes: when local education counts.
PMID- 25847971
TI - Breaking the allergic response by disrupting antibody glycosylation.
PMID- 25847972
TI - MAVS Promotes Inflammasome Activation by Targeting ASC for K63-Linked
Ubiquitination via the E3 Ligase TRAF3.
AB - Stringent control of inflammasome signaling pathway is important for maintaining
immunological balance, yet the molecular mechanisms responsible for its tight
regulation are still poorly understood. In this study, we found that the
signaling pathway dependent on mitochondrial antiviral signaling protein (MAVS)
was required for the optimal activation of apoptosis-associated specklike protein
(ASC)-dependent inflammasome. In particular, TNFR-associated factor 3 was found
to be a direct E3 ligase for ASC. Ubiquitination of ASC at Lys(174) was critical
for speck formation and inflammasome activation. Deficiency in MAVS or TNFR
associated factor 3 impaired ASC ubiquitination and cytosolic aggregates
formation, resulting in reduced inflammasome response upon RNA virus infection.
This study has identified a previously unrecognized role of MAVS in the
regulation of inflammasome signaling and provided molecular insight into the
mechanisms by which ubiquitination of ASC controls inflammasome activity through
the formation of ASC specks.
PMID- 25847973
TI - IL-33 Enhances Host Tolerance to Candida albicans Kidney Infections through
Induction of IL-13 Production by CD4+ T Cells.
AB - Susceptibility to systemic Candida albicans infection is determined by immune
resistance, as well as by the ability to control Candida-induced
immunopathologies. We showed previously that exogenous IL-33 can increase
resistance to peritoneal C. albicans infection by regulating multiple steps of
the neutrophil anti-Candida response. In this study, using a mouse model of
systemic candidiasis, we observed that IL-33 administration limited fungal burden
and inflammation and increased survival. In kidneys, IL-33 seemed to directly act
on neutrophils and CD4(+) T cells: IL-33 administration enhanced fungal clearance
by increasing neutrophil phagocytic activity without which Candida proliferation
was uncontrollable. In contrast, IL-33 stimulated CD4(+) T cells to produce IL
13, which, in turn, drove the polarization of macrophages toward the M2 type.
Furthermore, the absence of IL-13 abolished IL-33-mediated polarization of M2
macrophages and renal functional recovery. In addition, IL-33 and IL-13 acted
synergistically to increase M2 macrophage polarization and its phagocytic
activity. Overall, this study identifies IL-33 as a cytokine that is able to
induce resistance and tolerance and suggests that targeting resistance and
tolerance simultaneously with therapeutic IL-33 may benefit patients with
systemic candidiasis.
PMID- 25847974
TI - EBV oncogene N-LMP1 induces CD4 T cell-mediated angiogenic blockade in the murine
tumor model.
AB - Antivascular immunity may provide long-term protection by preventing
neovascularization that precedes tumor progression. Although the tumorigenesis
promoted by EBV-encoded oncogene latent membrane protein 1 derived from Taiwanese
nasopharyngeal carcinoma (N-LMP1) has been demonstrated, the potential of N-LMP1
for inducing immune surveillance remains elusive. In this article, we describe
the immunogenicity of N-LMP1 (1510) and its induction of antivascular immunity in
a transplantable tumor model in immunocompetent BALB/c mice. The immunogenicity
of N-LMP1 was evaluated on the basis of tumor rejection following immunization.
The impact of the immunization on the dynamics of tumor angiogenesis was assessed
by temporal noninvasive dynamic contrast-enhanced magnetic resonance imaging and
was further confirmed by histologic study and vascular count. Through the
experiments of in vivo depletion and adoptive transfer, CD4 T cells were
identified as effectors that depend on IFN-gamma for tumor prevention. The
response was further verified by the identification of an MHC H-2 I-E(d)
restricted peptide derived from N-LMP1 and by the immunization of mice with N
LMP1 peptide-loaded dendritic cells. These studies provide insight into N-LMP1
specific immunity in vivo, which suggests that CD4 T cells may play an important
role in angiogenic surveillance against LMP1-associated cancer via tumor stroma
targeting.
PMID- 25847975
TI - CCL7 and IRF-7 Mediate Hallmark Inflammatory and IFN Responses following
Rhinovirus 1B Infection.
AB - Rhinovirus (RV) infections are common and have the potential to exacerbate
asthma. We have determined the lung transcriptome in RV strain 1B-infected naive
BALB/c mice (nonallergic) and identified CCL7 and IFN regulatory factor (IRF)-7
among the most upregulated mRNA transcripts in the lung. To investigate their
roles we employed anti-CCL7 Abs and an IRF-7-targeting small interfering RNA in
vivo. Neutralizing CCL7 or inhibiting IRF-7 limited neutrophil and macrophage
influx and IFN responses in nonallergic mice. Neutralizing CCL7 also reduced
activation of NF-kappaB p65 and p50 subunits, as well as airway hyperreactivity
(AHR) in nonallergic mice. However, neither NF-kappaB subunit activation nor AHR
was abolished with infection of allergic mice after neutralizing CCL7, despite a
reduction in the number of neutrophils, macrophages, and eosinophils. IRF-7 small
interfering RNA primarily suppressed IFN-alpha and IFN-beta levels during
infection of allergic mice. Our data highlight a pivotal role of CCL7 and IRF-7
in RV-induced inflammation and IFN responses and link NF-kappaB signaling to the
development of AHR.
PMID- 25847976
TI - The world alliance against antibiotic resistance: consensus for a declaration.
AB - Antibiotic resistance is increasing worldwide and has become a very important
threat to public health. The overconsumption of antibiotics is the most important
cause of this problem. We created a World Alliance Against Antibiotic Resistance
(WAAAR), which now includes 720 people from 55 different countries and is
supported by 145 medical societies or various groups. In June 2014, WAAAR
launched a declaration against antibiotic resistance. This article describes the
process and the content of this declaration.
PMID- 25847977
TI - Clinical outcomes associated with respiratory virus detection before allogeneic
hematopoietic stem cell transplant.
AB - BACKGROUND: The management of respiratory virus infections prior to hematopoietic
cell transplant (HCT) is difficult. We examined whether respiratory virus
detection before HCT influenced the requirement for bronchoscopy,
hospitalization, and overall survival following HCT. METHODS: Pre-HCT and weekly
post-HCT nasal washes were collected through day 100 from patients with and
without symptoms. Samples were tested by multiplex polymerase chain reaction for
respiratory syncytial virus, parainfluenza viruses 1-4, influenza A and B, human
metapneumovirus, adenovirus, and human rhinoviruses, coronaviruses, and
bocavirus. RESULTS: Of 458 patients, 116 (25%) had respiratory viruses detected
pre-HCT. Overall, patients with viruses detected pre-HCT had fewer days alive and
out of the hospital and lower survival at day 100 (adjusted hazard ratio [aHR],
2.4; 95% confidence interval [CI], 1.3-4.5; P = .007) than patients with negative
samples; this risk was also present with rhinovirus alone (aHR for mortality,
2.6; 95% CI, 1.2-5.5; P = .01). No difference in bronchoscopy incidence was seen
in patients with and without respiratory viruses (aHR, 1.3; 95% CI, .8-2.0; P =
.32). In symptomatic patients, those with respiratory viruses detected had
increased overall mortality compared with patients without viruses detected
(unadjusted HR, 3.5; 95% CI, 1.0-12.1; P = .05); among asymptomatic patients,
detection of respiratory viruses was not associated with increased mortality.
CONCLUSIONS: These data support routine testing for respiratory viruses among
symptomatic patients before HCT, and delay of transplant with virus detection
when feasible, even for detection of rhinovirus alone. Further study is needed to
address whether asymptomatic patients should undergo screening for respiratory
virus detection before HCT.
PMID- 25847978
TI - Back to the future: improving the use of guidelines-recommended coronary disease
secondary prevention at the dawn of the precision medicine era.
PMID- 25847980
TI - Percutaneous interventions in aortic disease.
PMID- 25847979
TI - Optimal medical therapy improves clinical outcomes in patients undergoing
revascularization with percutaneous coronary intervention or coronary artery
bypass grafting: insights from the Synergy Between Percutaneous Coronary
Intervention with TAXUS and Cardiac Surgery (SYNTAX) trial at the 5-year follow
up.
AB - BACKGROUND: There is a paucity of data on the use of optimal medical therapy
(OMT) in patients with complex coronary artery disease undergoing
revascularization with percutaneous coronary intervention or coronary artery
bypass grafting (CABG) and its long-term prognostic significance. METHODS AND
RESULTS: The Synergy Between Percutaneous Coronary Intervention With TAXUS and
Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of
patients (n=1800) with complex coronary disease randomized to revascularization
with percutaneous coronary intervention or CABG. Detailed drug history was
collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3
year, and 5-year follow-ups. OMT was defined as the combination of at least 1
antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme
inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were
stratified by OMT and non-OMT. OMT was underused in patients treated with
coronary revascularization, especially CABG. OMT was an independent predictor of
survival. OMT was associated with a significant reduction in mortality (hazard
ratio, 0.64; 95% confidence interval, 0.48-0.85; P=0.002) and composite end point
of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence
interval, 0.58-0.92; P=0.007) at the 5-year follow-up. The treatment effect with
OMT (36% relative reduction in mortality over 5 years) was greater than the
treatment effect of revascularization strategy (26% relative reduction in
mortality with CABG versus percutaneous coronary intervention over 5 years). On
stratified analysis, all the components of OMT were important for reducing
adverse outcomes regardless of revascularization strategy. CONCLUSIONS: The use
of OMT remains low in patients with complex coronary disease requiring coronary
intervention with percutaneous coronary intervention and even lower in patients
treated with CABG. Lack of OMT is associated with adverse clinical outcomes.
Targeted strategies to improve OMT use in postrevascularization patients are
warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
Unique identifier: NCT00114972.
PMID- 25847981
TI - ECG response: April 7, 2015.
PMID- 25847983
TI - "Prancing" heart with pericardial injury.
PMID- 25847982
TI - Coronary artery rupture caused by stent infection: a rare complication.
PMID- 25847984
TI - Letter by Usui et al regarding article, "Inhibition of interleukin-1beta
decreases aneurysm formation and progression in a novel model of thoracic aortic
aneurysm".
PMID- 25847985
TI - Response to letter regarding article, "Inhibition of interleukin-1beta decreases
aneurysm formation and progression in a novel model of thoracic aortic aneurysm".
PMID- 25847986
TI - Correction. 9-Cis retinoic acid promotes lymphangiogenesis and enhances lymphatic
vessel regeneration: therapeutic implications of 9-Cis retinoic acid for
secondary lymphedema.
PMID- 25847987
TI - Correction. Cumulative effect of psychosocial factors in youth on ideal
cardiovascular health in adulthood: the Cardiovascular Risk in Young Finns Study.
PMID- 25847989
TI - Next-Generation Sequencing: Targeting Targeted Therapies.
AB - Next-generation sequencing (NGS) has given new perspective in oncology. With the
ongoing development of targeted therapies, NGS is evolving molecular diagnostics
by providing comprehensive interrogation of clinically actionable genomic
aberrations in tumors. Having this assay as the primary testing method produces
clinically beneficial results. See related article by Drilon et al., p. 3631.
PMID- 25847988
TI - Sudden cardiac arrest during sports activity in middle age.
AB - BACKGROUND: Sports-associated sudden cardiac arrests (SCAs) occur mostly during
middle age. We sought to determine the burden, characteristics, and outcomes of
SCA during sports among middle-aged residents of a large US community. METHODS
AND RESULTS: Patients with SCA who were 35 to 65 years of age were identified in
a large, prospective, population-based study (2002-2013), with systematic and
comprehensive assessment of their lifetime medical history. Of the 1247 SCA
cases, 63 (5%) occurred during sports activities at a mean age of 51.1+/-8.8
years, yielding an incidence of 21.7 (95% confidence interval, 8.1-35.4) per 1
million per year. The incidence varied significantly by sex, with a higher
incidence among men (relative risk, 18.68; 95% confidence interval, 2.50-139.56)
for sports SCAs compared with all other SCAs (relative risk 2.58; 95% confidence
interval, 2.12-3.13). Sports SCA was also more likely to be a witnessed event
(87% versus 53%; P<0.001) with cardiopulmonary resuscitation (44% versus 25%;
P=0.001) and ventricular fibrillation (84% versus 51%; P<0.0001). Survival to
hospital discharge was higher for sports-associated SCA (23.2% versus 13.6%;
P=0.04). Sports SCA cases presented with known preexisting cardiac disease in 16%
and >=1 cardiovascular risk factors in 56%, and overall, 36% of cases had typical
cardiovascular symptoms during the week preceding the SCA. CONCLUSIONS: Sports
associated SCA in middle age represents a relatively small proportion of the
overall SCA burden, reinforcing the idea of the high-benefit, low-risk nature of
sports activity. Especially in light of current population aging trends, our
findings emphasize that targeted education could maximize both safety and
acceptance of sports activity in the older athlete.
PMID- 25847990
TI - Noninvasive prenatal diagnosis of duchenne muscular dystrophy: comprehensive
genetic diagnosis in carrier, proband, and fetus.
AB - BACKGROUND: Noninvasive prenatal diagnosis of monogenic disorders using maternal
plasma and targeted massively parallel sequencing is being investigated actively.
We previously demonstrated that comprehensive genetic diagnosis of a Duchenne
muscular dystrophy (DMD) patient is feasible using a single targeted sequencing
platform. Here we demonstrate the applicability of this approach to carrier
detection and noninvasive prenatal diagnosis. METHODS: Custom solution-based
target enrichment was designed to cover the entire dystrophin (DMD) gene region.
Targeted massively parallel sequencing was performed using genomic DNA from 4
mother and proband pairs to test whether carrier status could be detected
reliably. Maternal plasma DNA at varying gestational weeks was collected from the
same families and sequenced using the same targeted platform to predict the
inheritance of the DMD mutation by their fetus. Overrepresentation of an
inherited allele was determined by comparing the allele fraction of 2 phased
haplotypes after examining and correcting for the recombination event. RESULTS:
The carrier status of deletion/duplication and point mutations was detected
reliably through using a single targeted massively parallel sequencing platform.
Whether the fetus had inherited the DMD mutation was predicted correctly in all 4
families as early as 6 weeks and 5 days of gestation. In one of these, detection
of the recombination event and reconstruction of the phased haplotype produced a
correct diagnosis. CONCLUSIONS: Noninvasive prenatal diagnosis of DMD is feasible
using a single targeted massively parallel sequencing platform with tiling
design.
PMID- 25847992
TI - Cities, traffic, and CO2: A multidecadal assessment of trends, drivers, and
scaling relationships.
AB - Emissions of CO2 from road vehicles were 1.57 billion metric tons in 2012,
accounting for 28% of US fossil fuel CO2 emissions, but the spatial distributions
of these emissions are highly uncertain. We develop a new emissions inventory,
the Database of Road Transportation Emissions (DARTE), which estimates CO2
emitted by US road transport at a resolution of 1 km annually for 1980-2012.
DARTE reveals that urban areas are responsible for 80% of on-road emissions
growth since 1980 and for 63% of total 2012 emissions. We observe nonlinearities
between CO2 emissions and population density at broad spatial/temporal scales,
with total on-road CO2 increasing nonlinearly with population density, rapidly up
to 1,650 persons per square kilometer and slowly thereafter. Per capita emissions
decline as density rises, but at markedly varying rates depending on existing
densities. We make use of DARTE's bottom-up construction to highlight the biases
associated with the common practice of using population as a linear proxy for
disaggregating national- or state-scale emissions. Comparing DARTE with existing
downscaled inventories, we find biases of 100% or more in the spatial
distribution of urban and rural emissions, largely driven by mismatches between
inventory downscaling proxies and the actual spatial patterns of vehicle activity
at urban scales. Given cities' dual importance as sources of CO2 and an emerging
nexus of climate mitigation initiatives, high-resolution estimates such as DARTE
are critical both for accurately quantifying surface carbon fluxes and for
verifying the effectiveness of emissions mitigation efforts at urban scales.
PMID- 25847991
TI - Glucocorticoid receptor regulates accurate chromosome segregation and is
associated with malignancy.
AB - The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily,
which controls programs regulating cell proliferation, differentiation, and
apoptosis. We have identified an unexpected role for GR in mitosis. We discovered
that specifically modified GR species accumulate at the mitotic spindle during
mitosis in a distribution that overlaps with Aurora kinases. We found that Aurora
A was required to mediate mitosis-driven GR phosphorylation, but not recruitment
of GR to the spindle. GR was necessary for mitotic progression, with increased
time to complete mitosis, frequency of mitotic aberrations, and death in mitosis
observed following GR knockdown. Complementation studies revealed an essential
role for the GR ligand-binding domain, but no clear requirement for ligand
binding in regulating chromosome segregation. The GR N-terminal domain, and
specifically phosphosites S203 and S211, were not required. Reduced GR expression
results in a cell cycle phenotype, with isolated cells from mouse and human
subjects showing changes in chromosome content over prolonged passage.
Furthermore, GR haploinsufficient mice have an increased incidence of tumor
formation, and, strikingly, these tumors are further depleted for GR, implying
additional GR loss as a consequence of cell transformation. We identified reduced
GR expression in a panel of human liver, lung, prostate, colon, and breast
cancers. We therefore reveal an unexpected role for the GR in promoting accurate
chromosome segregation during mitosis, which is causally linked to tumorigenesis,
making GR an authentic tumor suppressor gene.
PMID- 25847993
TI - Rgg protein structure-function and inhibition by cyclic peptide compounds.
AB - Peptide pheromone cell-cell signaling (quorum sensing) regulates the expression
of diverse developmental phenotypes (including virulence) in Firmicutes, which
includes common human pathogens, e.g., Streptococcus pyogenes and Streptococcus
pneumoniae. Cytoplasmic transcription factors known as "Rgg proteins" are peptide
pheromone receptors ubiquitous in Firmicutes. Here we present X-ray crystal
structures of a Streptococcus Rgg protein alone and in complex with a tight
binding signaling antagonist, the cyclic undecapeptide cyclosporin A. To our
knowledge, these represent the first Rgg protein X-ray crystal structures. Based
on the results of extensive structure-function analysis, we reveal the peptide
pheromone-binding site and the mechanism by which cyclosporin A inhibits
activation of the peptide pheromone receptor. Guided by the Rgg-cyclosporin A
complex structure, we predicted that the nonimmunosuppressive cyclosporin A
analog valspodar would inhibit Rgg activation. Indeed, we found that, like
cyclosporin A, valspodar inhibits peptide pheromone activation of conserved Rgg
proteins in medically relevant Streptococcus species. Finally, the crystal
structures presented here revealed that the Rgg protein DNA-binding domains are
covalently linked across their dimerization interface by a disulfide bond formed
by a highly conserved cysteine. The DNA-binding domain dimerization interface
observed in our structures is essentially identical to the interfaces previously
described for other members of the XRE DNA-binding domain family, but the
presence of an intermolecular disulfide bond buried in this interface appears to
be unique. We hypothesize that this disulfide bond may, under the right
conditions, affect Rgg monomer-dimer equilibrium, stabilize Rgg conformation, or
serve as a redox-sensitive switch.
PMID- 25847994
TI - Long-acting progestin-only contraceptives impair endometrial vasculature by
inhibiting uterine vascular smooth muscle cell survival.
AB - Molecular mechanisms responsible for abnormal endometrial vasculature in women
receiving long-acting progestin-only contraceptives (LAPCs) are unknown. We
hypothesize that LAPCs impair vascular smooth muscle cell (VSMC) and pericyte
proliferation and migration producing thin-walled hyperdilated fragile
microvessels prone to bleeding. Proliferating cell nuclear antigen (PCNA) and
alpha-smooth muscle actin (alphaSMA) double-immunostaining assessed VSMC
differentiation and proliferation in endometria from women before and after
DepoProvera (Depo) treatment and from oophorectomized guinea pigs (OVX-GPs)
treated with vehicle, estradiol (E2), medroxyprogesterone acetate (MPA), or
E2+MPA. Whole-genome profiling, proliferation, and migration assays were
performed on cultured VSMCs treated with MPA or etonogestrel (ETO). Endometrial
vessels of Depo-administered women displayed reduced alphaSMA immunoreactivity
and fewer PCNA (+) nuclei among alphaSMA (+) cells (P < 0.008). Microarray
analysis of VSMCs identified several MPA- and ETO-altered transcripts regulated
by STAT1 signaling (P < 2.22 * 10(-6)), including chemokine (C-C motif) ligand 2
(CCL2). Both MPA and ETO reduce VSMC proliferation and migration (P < 0.001).
Recombinant CCL2 reversed this progestin-mediated inhibition, whereas a STAT1
inhibitor abolished the CCL2 effect. Similarly, the endometria of MPA treated OVX
GPs displayed decreased alphaSMA staining and fewer PCNA (+) nuclei in VSMC (P <
0.005). In conclusion, LAPCs promote abnormal endometrial vessel formation by
inhibiting VSMC proliferation and migration.
PMID- 25847995
TI - US protected lands mismatch biodiversity priorities.
AB - Because habitat loss is the main cause of extinction, where and how much society
chooses to protect is vital for saving species. The United States is well
positioned economically and politically to pursue habitat conservation should it
be a societal goal. We assessed the US protected area portfolio with respect to
biodiversity in the country. New synthesis maps for terrestrial vertebrates,
freshwater fish, and trees permit comparison with protected areas to identify
priorities for future conservation investment. Although the total area protected
is substantial, its geographic configuration is nearly the opposite of patterns
of endemism within the country. Most protected lands are in the West, whereas the
vulnerable species are largely in the Southeast. Private land protections are
significant, but they are not concentrated where the priorities are. To
adequately protect the nation's unique biodiversity, we recommend specific areas
deserving additional protection, some of them including public lands, but many
others requiring private investment.
PMID- 25847996
TI - Stress sigma factor RpoS degradation and translation are sensitive to the state
of central metabolism.
AB - RpoS, the stationary phase/stress sigma factor of Escherichia coli, regulates a
large cohort of genes important for the cell to deal with suboptimal conditions.
Its level increases quickly in the cell in response to many stresses and returns
to low levels when growth resumes. Increased RpoS results from increased
translation and decreased RpoS degradation. Translation is positively regulated
by small RNAs (sRNAs). Protein stability is positively regulated by anti
adaptors, which prevent the RssB adaptor-mediated degradation of RpoS by the
ClpXP protease. Inactivation of aceE, a subunit of pyruvate dehydrogenase (PDH),
was found to increase levels of RpoS by affecting both translation and protein
degradation. The stabilization of RpoS in aceE mutants is dependent on increased
transcription and translation of IraP and IraD, two known anti-adaptors. The aceE
mutation also leads to a significant increase in rpoS translation. The sRNAs
known to positively regulate RpoS are not responsible for the increased
translation; sequences around the start codon are sufficient for the induction of
translation. PDH synthesizes acetyl-CoA; acetate supplementation allows the cell
to synthesize acetyl-CoA by an alternative, less favored pathway, in part
dependent upon RpoS. Acetate addition suppressed the effects of the aceE mutant
on induction of the anti-adaptors, RpoS stabilization, and rpoS translation.
Thus, the bacterial cell responds to lowered levels of acetyl-CoA by inducing
RpoS, allowing reprogramming of E. coli metabolism.
PMID- 25847998
TI - Homologous ligands accommodated by discrete conformations of a buried cavity.
AB - Conformational change in protein-ligand complexes is widely modeled, but the
protein accommodation expected on binding a congeneric series of ligands has
received less attention. Given their use in medicinal chemistry, there are
surprisingly few substantial series of congeneric ligand complexes in the Protein
Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in
single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed
cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate
benzene but, even with toluene, larger cavity conformations become observable in
the electron density, and over the series two other major conformations are
observed. These involve discrete changes in main-chain conformation, expanding
the site; few continuous changes in the site are observed. In most structures,
two discrete protein conformations are observed simultaneously, and energetic
considerations suggest that these conformations are low in energy relative to the
ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that
these three conformations dominate the previously determined structures, largely
modeled in a single conformation. An investigation of the few congeneric series
in the PDB suggests that discrete changes are common adaptations to a series of
growing ligands. The discrete, but relatively few, conformational states observed
here, and their energetic accessibility, may have implications for anticipating
protein conformational change in ligand design.
PMID- 25847997
TI - Cortical activity is more stable when sensory stimuli are consciously perceived.
AB - According to recent evidence, stimulus-tuned neurons in the cerebral cortex
exhibit reduced variability in firing rate across trials, after the onset of a
stimulus. However, in order for a reduction in variability to be directly
relevant to perception and behavior, it must be realized within trial--the
pattern of activity must be relatively stable. Stability is characteristic of
decision states in recurrent attractor networks, and its possible relevance to
conscious perception has been suggested by theorists. However, it is difficult to
measure on the within-trial time scales and broadly distributed spatial scales
relevant to perception. We recorded simultaneous magneto- and
electroencephalography (MEG and EEG) data while subjects observed threshold-level
visual stimuli. Pattern-similarity analyses applied to the data from MEG
gradiometers uncovered a pronounced decrease in variability across trials after
stimulus onset, consistent with previous single-unit data. This was followed by a
significant divergence in variability depending upon subjective report
(seen/unseen), with seen trials exhibiting less variability. Applying the same
analysis across time, within trial, we found that the latter effect coincided in
time with a difference in the stability of the pattern of activity. Stability
alone could be used to classify data from individual trials as "seen" or
"unseen." The same metric applied to EEG data from patients with disorders of
consciousness exposed to auditory stimuli diverged parametrically according to
clinically diagnosed level of consciousness. Differences in signal strength could
not account for these results. Conscious perception may involve the transient
stabilization of distributed cortical networks, corresponding to a global brain
scale decision.
PMID- 25847999
TI - Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.
AB - Alzheimer's disease (AD) is one of most devastating diseases affecting elderly
people. Amyloid-beta (Abeta) accumulation and the downstream pathological events
such as oxidative stress play critical roles in pathogenesis of AD. Lessons from
failures of current clinical trials suggest that targeting multiple key pathways
of the AD pathogenesis is necessary to halt the disease progression. Here we show
that Edaravone, a free radical scavenger that is marketed for acute ischemic
stroke, has a potent capacity of inhibiting Abeta aggregation and attenuating
Abeta-induced oxidation in vitro. When given before or after the onset of Abeta
deposition via i.p. injection, Edaravone substantially reduces Abeta deposition,
alleviates oxidative stress, attenuates the downstream pathologies including Tau
hyperphosphorylation, glial activation, neuroinflammation, neuronal loss,
synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice.
Oral administration of Edaravone also ameliorates the AD-like pathologies and
memory deficits of the mice. These findings suggest that Edaravone holds a
promise as a therapeutic agent for AD by targeting multiple key pathways of the
disease pathogenesis.
PMID- 25848001
TI - Time-dependent sequestration of RVE8 by LNK proteins shapes the diurnal
oscillation of anthocyanin biosynthesis.
AB - Circadian clocks sustain 24-h rhythms in physiology and metabolism that are
synchronized with the day/night cycle. In plants, the regulatory network
responsible for the generation of rhythms has been broadly investigated over the
past years. However, little is known about the intersecting pathways that link
the environmental signals with rhythms in cellular metabolism. Here, we examine
the role of the circadian components REVEILLE8/LHY-CCA1-LIKE5 (RVE8/LCL5) and
NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED genes (LNK) shaping the diurnal
oscillation of the anthocyanin metabolic pathway. Around dawn, RVE8 up-regulates
anthocyanin gene expression by directly associating to the promoters of a subset
of anthocyanin biosynthetic genes. The up-regulation is overcome at midday by the
repressing activity of LNK proteins, as inferred by the increased anthocyanin
gene expression in lnk1/lnk2 double mutant plants. Chromatin immunoprecipitation
assays using LNK and RVE8 misexpressing plants show that RVE8 binding to target
promoters is precluded in LNK overexpressing plants and conversely, binding is
enhanced in the absence of functional LNKs, which provides a mechanism by which
LNKs antagonize RVE8 function in the regulation of anthocyanin accumulation.
Based on their previously described transcriptional coactivating function, our
study defines a switch in the regulatory activity of RVE8-LNK interaction, from a
synergic coactivating role of evening-expressed clock genes to a repressive
antagonistic function modulating anthocyanin biosynthesis around midday.
PMID- 25848000
TI - Maternal and zygotic Zfp57 modulate NOTCH signaling in cardiac development.
AB - Zfp57 is a maternal-zygotic effect gene that maintains genomic imprinting. Here
we report that Zfp57 mutants exhibited a variety of cardiac defects including
atrial septal defect (ASD), ventricular septal defect (VSD), thin myocardium, and
reduced trabeculation. Zfp57 maternal-zygotic mutant embryos displayed more
severe phenotypes with higher penetrance than the zygotic ones. Cardiac
progenitor cells exhibited proliferation and differentiation defects in Zfp57
mutants. ZFP57 is a master regulator of genomic imprinting, so the DNA
methylation imprint was lost in embryonic heart without ZFP57. Interestingly, the
presence of imprinted DLK1, a target of ZFP57, correlated with NOTCH1 activation
in cardiac cells. These results suggest that ZFP57 may modulate NOTCH signaling
during cardiac development. Indeed, loss of ZFP57 caused loss of NOTCH1
activation in embryonic heart with more severe loss observed in the maternal
zygotic mutant. Maternal and zygotic functions of Zfp57 appear to play redundant
roles in NOTCH1 activation and cardiomyocyte differentiation. This serves as an
example of a maternal effect that can influence mammalian organ development. It
also links genomic imprinting to NOTCH signaling and particular developmental
functions.
PMID- 25848002
TI - Structural basis for substrate specificity of an amino acid ABC transporter.
AB - ATP-binding cassette (ABC) transporters are ubiquitous integral membrane proteins
that translocate a variety of substrates, ranging from ions to macromolecules,
either out of or into the cytosol (hence defined as importers or exporters,
respectively). It has been demonstrated that ABC exporters and importers function
through a common mechanism involving conformational switches between inward
facing and outward-facing states; however, the mechanism underlying their
functions, particularly substrate recognition, remains elusive. Here we report
the structures of an amino acid ABC importer Art(QN)2 from Thermoanaerobacter
tengcongensis composed of homodimers each of the transmembrane domain ArtQ and
the nucleotide-binding domain ArtN, either in its apo form or in complex with
substrates (Arg, His) and/or ATPs. The structures reveal that the straddling of
the TMDs around the twofold axis forms a substrate translocation pathway across
the membrane. Interestingly, each TMD has a negatively charged pocket that
together create a negatively charged internal tunnel allowing amino acids
carrying positively charged groups to pass through. Our structural and functional
studies provide a better understanding of how ABC transporters select and
translocate their substrates.
PMID- 25848003
TI - New functional insights into the internal architecture of the laminated anchor
spicules of Euplectella aspergillum.
AB - To adapt to a wide range of physically demanding environmental conditions,
biological systems have evolved a diverse variety of robust skeletal
architectures. One such example, Euplectella aspergillum, is a sediment-dwelling
marine sponge that is anchored into the sea floor by a flexible holdfast
apparatus consisting of thousands of anchor spicules (long, hair-like glassy
fibers). Each spicule is covered with recurved barbs and has an internal
architecture consisting of a solid core of silica surrounded by an assembly of
coaxial silica cylinders, each of which is separated by a thin organic layer. The
thickness of each silica cylinder progressively decreases from the spicule's core
to its periphery, which we hypothesize is an adaptation for redistributing
internal stresses, thus increasing the overall strength of each spicule. To
evaluate this hypothesis, we created a spicule structural mechanics model, in
which we fixed the radii of the silica cylinders such that the force transmitted
from the surface barbs to the remainder of the skeletal system was maximized.
Compared with measurements of these parameters in the native sponge spicules, our
modeling results correlate remarkably well, highlighting the beneficial nature of
this elastically heterogeneous lamellar design strategy. The structural
principles obtained from this study thus provide potential design insights for
the fabrication of high-strength beams for load-bearing applications through the
modification of their internal architecture, rather than their external geometry.
PMID- 25848004
TI - Octopamine mediates starvation-induced hyperactivity in adult Drosophila.
AB - Starved animals often exhibit elevated locomotion, which has been speculated to
partly resemble foraging behavior and facilitate food acquisition and energy
intake. Despite its importance, the neural mechanism underlying this behavior
remains unknown in any species. In this study we confirmed and extended previous
findings that starvation induced locomotor activity in adult fruit flies
Drosophila melanogaster. We also showed that starvation-induced hyperactivity was
directed toward the localization and acquisition of food sources, because it
could be suppressed upon the detection of food cues via both central nutrient
sensing and peripheral sweet-sensing mechanisms, via induction of food ingestion.
We further found that octopamine, the insect counterpart of vertebrate
norepinephrine, as well as the neurons expressing octopamine, were both necessary
and sufficient for starvation-induced hyperactivity. Octopamine was not required
for starvation-induced changes in feeding behaviors, suggesting independent
regulations of energy intake behaviors upon starvation. Taken together, our
results establish a quantitative behavioral paradigm to investigate the
regulation of energy homeostasis by the CNS and identify a conserved neural
substrate that links organismal metabolic state to a specific behavioral output.
PMID- 25848005
TI - Cadmium-cysteine coordination in the BK inner pore region and its structural and
functional implications.
AB - To probe structure and gating-associated conformational changes in BK-type
potassium (BK) channels, we examined consequences of Cd(2+) coordination with
cysteines introduced at two positions in the BK inner pore. At V319C, the
equivalent of valine in the conserved Kv proline-valine-proline (PVP) motif,
Cd(2+) forms intrasubunit coordination with a native glutamate E321, which would
place the side chains of V319C and E321 much closer together than observed in
voltage-dependent K(+) (Kv) channel structures, requiring that the proline
between V319C and E321 introduces a kink in the BK S6 inner helix sharper than
that observed in Kv channel structures. At inner pore position A316C, Cd(2+)
binds with modest state dependence, suggesting the absence of an ion permeation
gate at the cytosolic side of BK channel. These results highlight fundamental
structural differences between BK and Kv channels in their inner pore region,
which likely underlie differences in voltage-dependent gating between these
channels.
PMID- 25848006
TI - Salmonella promotes virulence by repressing cellulose production.
AB - Cellulose is the most abundant organic polymer on Earth. In bacteria, cellulose
confers protection against environmental insults and is a constituent of biofilms
typically formed on abiotic surfaces. We report that, surprisingly, Salmonella
enterica serovar Typhimurium makes cellulose when inside macrophages. We
determine that preventing cellulose synthesis increases virulence, whereas
stimulation of cellulose synthesis inside macrophages decreases virulence. An
attenuated mutant lacking the mgtC gene exhibited increased cellulose levels due
to increased expression of the cellulose synthase gene bcsA and of cyclic
diguanylate, the allosteric activator of the BcsA protein. Inactivation of bcsA
restored wild-type virulence to the Salmonella mgtC mutant, but not to other
attenuated mutants displaying a wild-type phenotype regarding cellulose. Our
findings indicate that a virulence determinant can promote pathogenicity by
repressing a pathogen's antivirulence trait. Moreover, they suggest that
controlling antivirulence traits increases long-term pathogen fitness by
mediating a trade-off between acute virulence and transmission.
PMID- 25848007
TI - Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest.
AB - The mechanism by which the healthy heart and brain die rapidly in the absence of
oxygen is not well understood. We performed continuous electrocardiography and
electroencephalography in rats undergoing experimental asphyxia and analyzed
cortical release of core neurotransmitters, changes in brain and heart electrical
activity, and brain-heart connectivity. Asphyxia stimulates a robust and
sustained increase of functional and effective cortical connectivity, an
immediate increase in cortical release of a large set of neurotransmitters, and a
delayed activation of corticocardiac functional and effective connectivity that
persists until the onset of ventricular fibrillation. Blocking the brain's
autonomic outflow significantly delayed terminal ventricular fibrillation and
lengthened the duration of detectable cortical activities despite the continued
absence of oxygen. These results demonstrate that asphyxia activates a
brainstorm, which accelerates premature death of the heart and the brain.
PMID- 25848008
TI - Estrogen receptor beta exon 3-deleted mouse: The importance of non-ERE pathways
in ERbeta signaling.
AB - In 1998, an estrogen receptor beta (ERbeta) knockout (KO) mouse was created by
interrupting the gene at the DNA binding domain (DBD) with a neocassette. The
mutant females were subfertile and there were abnormalities in the brain,
prostate, lung, colon, and immune system. In 2008, another ERbeta mutant mouse
was generated by deleting ERbeta exon 3 which encodes the first zinc finger in
the DBD. The female mice of this strain were unable to ovulate but were otherwise
normal. The differences in the phenotypes of the two KO strains, have led to
questions about the physiological function of ERbeta. In the present study, we
created an ERbeta exon 3-deleted mouse (ERbeta-Deltaex3) and confirmed that the
only observable defect was anovulation. Despite the two in-frame stop codons
introduced by splicing between exons 2 and 4, an ERbeta protein was expressed in
nuclei of prostate epithelial cells. Using two different anti-ERbeta antibodies,
we showed that an in-frame ligand binding domain and C terminus were present in
the ERbeta-Deltaex3 protein. Moreover, with nuclear extracts from ERbeta-Deltaex3
prostates, there was an ERbeta-dependent retardation of migration of activator
protein-1 response elements in EMSA. Unlike the original knockout mouse,
expression of Ki67, androgen receptor, and Dachshund-1 in prostate epithelium was
not altered in the ERbeta-Deltaex3 mouse. We conclude that very little of ERbeta
transcriptional activity depends on binding to classical estrogen response
elements (EREs).
PMID- 25848009
TI - Cadherin-related family member 3, a childhood asthma susceptibility gene product,
mediates rhinovirus C binding and replication.
AB - Members of rhinovirus C (RV-C) species are more likely to cause wheezing
illnesses and asthma exacerbations compared with other rhinoviruses. The cellular
receptor for these viruses was heretofore unknown. We report here that expression
of human cadherin-related family member 3 (CDHR3) enables the cells normally
unsusceptible to RV-C infection to support both virus binding and replication. A
coding single nucleotide polymorphism (rs6967330, C529Y) was previously linked to
greater cell-surface expression of CDHR3 protein, and an increased risk of
wheezing illnesses and hospitalizations for childhood asthma. Compared with wild
type CDHR3, cells transfected with the CDHR3-Y529 variant had about 10-fold
increases in RV-C binding and progeny yields. We developed a transduced HeLa cell
line (HeLa-E8) stably expressing CDHR3-Y529 that supports RV-C propagation in
vitro. Modeling of CDHR3 structure identified potential binding sites that could
impact the virus surface in regions that are highly conserved among all RV-C
types. Our findings identify that the asthma susceptibility gene product CDHR3
mediates RV-C entry into host cells, and suggest that rs6967330 mutation could be
a risk factor for RV-C wheezing illnesses.
PMID- 25848010
TI - Insights into the origins of fish hunting in venomous cone snails from studies of
Conus tessulatus.
AB - Prey shifts in carnivorous predators are events that can initiate the accelerated
generation of new biodiversity. However, it is seldom possible to reconstruct how
the change in prey preference occurred. Here we describe an evolutionary "smoking
gun" that illuminates the transition from worm hunting to fish hunting among
marine cone snails, resulting in the adaptive radiation of fish-hunting lineages
comprising ~100 piscivorous Conus species. This smoking gun is delta-conotoxin
TsVIA, a peptide from the venom of Conus tessulatus that delays inactivation of
vertebrate voltage-gated sodium channels. C. tessulatus is a species in a worm
hunting clade, which is phylogenetically closely related to the fish-hunting cone
snail specialists. The discovery of a delta-conotoxin that potently acts on
vertebrate sodium channels in the venom of a worm-hunting cone snail suggests
that a closely related ancestral toxin enabled the transition from worm hunting
to fish hunting, as delta-conotoxins are highly conserved among fish hunters and
critical to their mechanism of prey capture; this peptide, delta-conotoxin TsVIA,
has striking sequence similarity to these delta-conotoxins from piscivorous cone
snail venoms. Calcium-imaging studies on dissociated dorsal root ganglion (DRG)
neurons revealed the peptide's putative molecular target (voltage-gated sodium
channels) and mechanism of action (inhibition of channel inactivation). The
results were confirmed by electrophysiology. This work demonstrates how
elucidating the specific interactions between toxins and receptors from
phylogenetically well-defined lineages can uncover molecular mechanisms that
underlie significant evolutionary transitions.
PMID- 25848011
TI - Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both
CDK4/6 and OCT2 functions.
AB - Acute kidney injury (AKI) is a potentially fatal syndrome characterized by a
rapid decline in kidney function caused by ischemic or toxic injury to renal
tubular cells. The widely used chemotherapy drug cisplatin accumulates
preferentially in the renal tubular cells and is a frequent cause of drug-induced
AKI. During the development of AKI the quiescent tubular cells reenter the cell
cycle. Strategies that block cell-cycle progression ameliorate kidney injury,
possibly by averting cell division in the presence of extensive DNA damage.
However, the early signaling events that lead to cell-cycle activation during AKI
are not known. In the current study, using mouse models of cisplatin
nephrotoxicity, we show that the G1/S-regulating cyclin-dependent kinase 4/6
(CDK4/6) pathway is activated in parallel with renal cell-cycle entry but before
the development of AKI. Targeted inhibition of CDK4/6 pathway by small-molecule
inhibitors palbociclib (PD-0332991) and ribociclib (LEE011) resulted in
inhibition of cell-cycle progression, amelioration of kidney injury, and improved
overall survival. Of additional significance, these compounds were found to be
potent inhibitors of organic cation transporter 2 (OCT2), which contributes to
the cellular accumulation of cisplatin and subsequent kidney injury. The unique
cell-cycle and OCT2-targeting activities of palbociclib and LEE011, combined with
their potential for clinical translation, support their further exploration as
therapeutic candidates for prevention of AKI.
PMID- 25848012
TI - Structure of CARDS toxin, a unique ADP-ribosylating and vacuolating cytotoxin
from Mycoplasma pneumoniae.
AB - Mycoplasma pneumoniae (Mp) infections cause tracheobronchitis and "walking"
pneumonia, and are linked to asthma and other reactive airway diseases. As part
of the infectious process, the bacterium expresses a 591-aa virulence factor with
both mono-ADP ribosyltransferase (mART) and vacuolating activities known as
Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX binds
to human surfactant protein A and annexin A2 on airway epithelial cells and is
internalized, leading to a range of pathogenetic events. Here we present the
structure of CARDS TX, a triangular molecule in which N-terminal mART and C
terminal tandem beta-trefoil domains associate to form an overall architecture
distinct from other well-recognized ADP-ribosylating bacterial toxins. We
demonstrate that CARDS TX binds phosphatidylcholine and sphingomyelin
specifically over other membrane lipids, and that cell surface binding and
internalization activities are housed within the C-terminal beta-trefoil domain.
The results enhance our understanding of Mp pathogenicity and suggest a novel
avenue for the development of therapies to treat Mp-associated asthma and other
acute and chronic airway diseases.
PMID- 25848013
TI - A modular toolkit to inhibit proline-rich motif-mediated protein-protein
interactions.
AB - Small-molecule competitors of protein-protein interactions are urgently needed
for functional analysis of large-scale genomics and proteomics data. Particularly
abundant, yet so far undruggable, targets include domains specialized in
recognizing proline-rich segments, including Src-homology 3 (SH3), WW, GYF, and
Drosophila enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) homology 1
(EVH1) domains. Here, we present a modular strategy to obtain an extendable
toolkit of chemical fragments (ProMs) designed to replace pairs of conserved
prolines in recognition motifs. As proof-of-principle, we developed a small,
selective, peptidomimetic inhibitor of Ena/VASP EVH1 domain interactions. Highly
invasive MDA MB 231 breast-cancer cells treated with this ligand showed
displacement of VASP from focal adhesions, as well as from the front of
lamellipodia, and strongly reduced cell invasion. General applicability of our
strategy is illustrated by the design of an ErbB4-derived ligand containing two
ProM-1 fragments, targeting the yes-associated protein 1 (YAP1)-WW domain with a
fivefold higher affinity.
PMID- 25848014
TI - Mimicking the magnetic properties of rare earth elements using superatoms.
AB - Rare earth elements (REs) consist of a very important group in the periodic table
that is vital to many modern technologies. The mining process, however, is
extremely damaging to the environment, making them low yield and very expensive.
Therefore, mimicking the properties of REs in a superatom framework is especially
valuable but at the same time, technically challenging and requiring advanced
concepts about manipulating properties of atom/molecular complexes. Herein, by
using photoelectron imaging spectroscopy, we provide original idea and direct
experimental evidence that chosen boron-doped clusters could mimic the magnetic
characteristics of REs. Specifically, the neutral LaB and NdB clusters are found
to have similar unpaired electrons and magnetic moments as their isovalent REs
(namely Nd and Eu, respectively), opening up the great possibility in
accomplishing rare earth mimicry. Extension of the superatom concept into the
rare earth group not only further shows the power and advance of this concept but
also, will stimulate more efforts to explore new superatomic clusters to mimic
the chemistry of these heavy atoms, which will be of great importance in
designing novel building blocks in the application of cluster-assembled
nanomaterials. Additionally, based on these experimental findings, a novel "magic
boron" counting rule is proposed to estimate the numbers of unpaired electrons in
diatomic LnB clusters.
PMID- 25848015
TI - High-yield hydrogen production from biomass by in vitro metabolic engineering:
Mixed sugars coutilization and kinetic modeling.
AB - The use of hydrogen (H2) as a fuel offers enhanced energy conversion efficiency
and tremendous potential to decrease greenhouse gas emissions, but producing it
in a distributed, carbon-neutral, low-cost manner requires new technologies.
Herein we demonstrate the complete conversion of glucose and xylose from plant
biomass to H2 and CO2 based on an in vitro synthetic enzymatic pathway. Glucose
and xylose were simultaneously converted to H2 with a yield of two H2 per carbon,
the maximum possible yield. Parameters of a nonlinear kinetic model were fitted
with experimental data using a genetic algorithm, and a global sensitivity
analysis was used to identify the enzymes that have the greatest impact on
reaction rate and yield. After optimizing enzyme loadings using this model,
volumetric H2 productivity was increased 3-fold to 32 mmol H2?L(-1)?h(-1). The
productivity was further enhanced to 54 mmol H2?L(-1)?h(-1) by increasing
reaction temperature, substrate, and enzyme concentrations--an increase of 67
fold compared with the initial studies using this method. The production of
hydrogen from locally produced biomass is a promising means to achieve global
green energy production.
PMID- 25848016
TI - Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated
by reducing Arc expression.
AB - Angelman syndrome (AS) is a neurodevelopmental disorder arising from loss-of
function mutations in the maternally inherited copy of the UBE3A gene, and is
characterized by an absence of speech, excessive laughter, cognitive delay, motor
deficits, and seizures. Despite the fact that the symptoms of AS occur in early
childhood, behavioral characterization of AS mouse models has focused primarily
on adult phenotypes. In this report we describe juvenile behaviors in AS mice
that are strain-independent and clinically relevant. We find that young AS mice,
compared with their wild-type littermates, produce an increased number of
ultrasonic vocalizations. In addition, young AS mice have defects in motor
coordination, as well as abnormal brain activity that results in an enhanced
seizure-like response to an audiogenic challenge. The enhanced seizure-like
activity, but not the increased ultrasonic vocalizations or motor deficits, is
rescued in juvenile AS mice by genetically reducing the expression level of the
activity-regulated cytoskeleton-associated protein, Arc. These findings suggest
that therapeutic interventions that reduce the level of Arc expression have the
potential to reverse the seizures associated with AS. In addition, the
identification of aberrant behaviors in young AS mice may provide clues regarding
the neural circuit defects that occur in AS and ultimately allow new approaches
for treating this disorder.
PMID- 25848017
TI - Exonuclease TREX1 degrades double-stranded DNA to prevent spontaneous lupus-like
inflammatory disease.
AB - The TREX1 gene encodes a potent DNA exonuclease, and mutations in TREX1 cause a
spectrum of lupus-like autoimmune diseases. Most lupus patients develop
autoantibodies to double-stranded DNA (dsDNA), but the source of DNA antigen is
unknown. The TREX1 D18N mutation causes a monogenic, cutaneous form of lupus
called familial chilblain lupus, and the TREX1 D18N enzyme exhibits dysfunctional
dsDNA-degrading activity, providing a link between dsDNA degradation and nucleic
acid-mediated autoimmune disease. We determined the structure of the TREX1 D18N
protein in complex with dsDNA, revealing how this exonuclease uses a novel DNA
unwinding mechanism to separate the polynucleotide strands for single-stranded
DNA (ssDNA) loading into the active site. The TREX1 D18N dsDNA interactions
coupled with catalytic deficiency explain how this mutant nuclease prevents dsDNA
degradation. We tested the effects of TREX1 D18N in vivo by replacing the TREX1
WT gene in mice with the TREX1 D18N allele. The TREX1 D18N mice exhibit systemic
inflammation, lymphoid hyperplasia, vasculitis, and kidney disease. The observed
lupus-like inflammatory disease is associated with immune activation, production
of autoantibodies to dsDNA, and deposition of immune complexes in the kidney.
Thus, dysfunctional dsDNA degradation by TREX1 D18N induces disease in mice that
recapitulates many characteristics of human lupus. Failure to clear DNA has long
been linked to lupus in humans, and these data point to dsDNA as a key substrate
for TREX1 and a major antigen source in mice with dysfunctional TREX1 enzyme.
PMID- 25848018
TI - Fishing amplifies forage fish population collapses.
AB - Forage fish support the largest fisheries in the world but also play key roles in
marine food webs by transferring energy from plankton to upper trophic-level
predators, such as large fish, seabirds, and marine mammals. Fishing can,
thereby, have far reaching consequences on marine food webs unless safeguards are
in place to avoid depleting forage fish to dangerously low levels, where
dependent predators are most vulnerable. However, disentangling the contributions
of fishing vs. natural processes on population dynamics has been difficult
because of the sensitivity of these stocks to environmental conditions. Here, we
overcome this difficulty by collating population time series for forage fish
populations that account for nearly two-thirds of global catch of forage fish to
identify the fingerprint of fisheries on their population dynamics. Forage fish
population collapses shared a set of common and unique characteristics: high
fishing pressure for several years before collapse, a sharp drop in natural
population productivity, and a lagged response to reduce fishing pressure. Lagged
response to natural productivity declines can sharply amplify the magnitude of
naturally occurring population fluctuations. Finally, we show that the magnitude
and frequency of collapses are greater than expected from natural productivity
characteristics and therefore, likely attributed to fishing. The durations of
collapses, however, were not different from those expected based on natural
productivity shifts. A risk-based management scheme that reduces fishing when
populations become scarce would protect forage fish and their predators from
collapse with little effect on long-term average catches.
PMID- 25848019
TI - Mosaic nature of the mitochondrial proteome: Implications for the origin and
evolution of mitochondria.
AB - Comparative studies of the mitochondrial proteome have identified a conserved
core of proteins descended from the alpha-proteobacterial endosymbiont that gave
rise to the mitochondrion and was the source of the mitochondrial genome in
contemporary eukaryotes. A surprising result of phylogenetic analyses is the
relatively small proportion (10-20%) of the mitochondrial proteome displaying a
clear alpha-proteobacterial ancestry. A large fraction of mitochondrial proteins
typically has detectable homologs only in other eukaryotes and is presumed to
represent proteins that emerged specifically within eukaryotes. A further
significant fraction of the mitochondrial proteome consists of proteins with
homologs in prokaryotes, but without a robust phylogenetic signal affiliating
them with specific prokaryotic lineages. The presumptive evolutionary source of
these proteins is quite different in contending models of mitochondrial origin.
PMID- 25848021
TI - Mechanical cloak design by direct lattice transformation.
AB - Spatial coordinate transformations have helped simplifying mathematical issues
and solving complex boundary-value problems in physics for decades already. More
recently, material-parameter transformations have also become an intuitive and
powerful engineering tool for designing inhomogeneous and anisotropic material
distributions that perform wanted functions, e.g., invisibility cloaking. A
necessary mathematical prerequisite for this approach to work is that the
underlying equations are form invariant with respect to general coordinate
transformations. Unfortunately, this condition is not fulfilled in elastic-solid
mechanics for materials that can be described by ordinary elasticity tensors.
Here, we introduce a different and simpler approach. We directly transform the
lattice points of a 2D discrete lattice composed of a single constituent
material, while keeping the properties of the elements connecting the lattice
points the same. After showing that the approach works in various areas, we focus
on elastic-solid mechanics. As a demanding example, we cloak a void in an
effective elastic material with respect to static uniaxial compression.
Corresponding numerical calculations and experiments on polymer structures made
by 3D printing are presented. The cloaking quality is quantified by comparing the
average relative SD of the strain vectors outside of the cloaked void with
respect to the homogeneous reference lattice. Theory and experiment agree and
exhibit very good cloaking performance.
PMID- 25848020
TI - Effective and lesion-free cutaneous influenza vaccination.
AB - The current study details efficient lesion-free cutaneous vaccination via vaccine
delivery into an array of micropores in the skin, instead of bolus injection at a
single site. Such delivery effectively segregated vaccine-induced inflammation,
resulting in rapid resolution of the inflammation, provided that distances
between any two micropores were sufficient. When the inoculation site was treated
by FDA-approved nonablative fractional laser (NAFL) before insertion of a PR8
model influenza vaccine-packaged, biodegradable microneedle array (MNs), mice
displayed vigorous antigen-uptake, eliciting strong Th1-biased immunity. These
animals were completely protected from homologous viral challenges, and fully or
partially protected from heterologous H1N1 and H3N2 viral challenges, whereas
mice receiving MNs alone suffered from severe illnesses or died of similar viral
challenges. NAFL-mediated adjuvanicity was ascribed primarily to dsDNA and other
"danger" signals released from laser-damaged skin cells. Thus, mice deficient in
dsDNA-sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways,
showed poor responses to NAFL. Importantly, with this novel approach both mice
and swine exhibited strong protective immunity without incurring any appreciable
skin irritation, in sharp contrast to the overt skin irritation caused by
intradermal injections. The effective lesion-free cutaneous vaccination merits
further clinical studies.
PMID- 25848022
TI - GEMM-I riboswitches from Geobacter sense the bacterial second messenger cyclic
AMP-GMP.
AB - Cyclic dinucleotides are an expanding class of signaling molecules that control
many aspects of bacterial physiology. A synthase for cyclic AMP-GMP (cAG, also
referenced as 3'-5', 3'-5' cGAMP) called DncV is associated with hyperinfectivity
of Vibrio cholerae but has not been found in many bacteria, raising questions
about the prevalence and function of cAG signaling. We have discovered that the
environmental bacterium Geobacter sulfurreducens produces cAG and uses a subset
of GEMM-I class riboswitches (GEMM-Ib, Genes for the Environment, Membranes, and
Motility) as specific receptors for cAG. GEMM-Ib riboswitches regulate genes
associated with extracellular electron transfer; thus cAG signaling may control
aspects of bacterial electrophysiology. These findings expand the role of cAG
beyond organisms that harbor DncV and beyond pathogenesis to microbial
geochemistry, which is important to environmental remediation and microbial fuel
cell development. Finally, we have developed an RNA-based fluorescent biosensor
for live-cell imaging of cAG. This selective, genetically encodable biosensor
will be useful to probe the biochemistry and cell biology of cAG signaling in
diverse bacteria.
PMID- 25848023
TI - Control of bacterial exoelectrogenesis by c-AMP-GMP.
AB - Major changes in bacterial physiology including biofilm and spore formation
involve signaling by the cyclic dinucleotides c-di-GMP and c-di-AMP. Recently,
another second messenger dinucleotide, c-AMP-GMP, was found to control chemotaxis
and colonization by Vibrio cholerae. We have identified a superregulon of genes
controlled by c-AMP-GMP in numerous Deltaproteobacteria, including Geobacter
species that use extracellular insoluble metal oxides as terminal electron
acceptors. This exoelectrogenic process has been studied for its possible utility
in energy production and bioremediation. Many genes involved in adhesion, pilin
formation, and others that are important for exoelectrogenesis are controlled by
members of a variant riboswitch class that selectively bind c-AMP-GMP. These RNAs
constitute, to our knowledge, the first known specific receptors for c-AMP-GMP
and reveal that this molecule is used by many bacteria to control specialized
physiological processes.
PMID- 25848024
TI - Virus decomposition provides an important contribution to benthic deep-sea
ecosystem functioning.
AB - Viruses are key biological agents of prokaryotic mortality in the world oceans,
particularly in deep-sea ecosystems where nearly all of the prokaryotic C
production is transformed into organic detritus. However, the extent to which the
decomposition of viral particles (i.e., organic material of viral origin)
influences the functioning of benthic deep-sea ecosystems remains completely
unknown. Here, using various independent approaches, we show that in deep-sea
sediments an important fraction of viruses, once they are released by cell lysis,
undergo fast decomposition. Virus decomposition rates in deep-sea sediments are
high even at abyssal depths and are controlled primarily by the extracellular
enzymatic activities that hydrolyze the proteins of the viral capsids. We
estimate that on a global scale the decomposition of benthic viruses releases ~37
50 megatons of C per year and thus represents an important source of labile
organic compounds in deep-sea ecosystems. Organic material released from
decomposed viruses is equivalent to 3 +/- 1%, 6 +/- 2%, and 12 +/- 3% of the
input of photosynthetically produced C, N, and P supplied through particles
sinking to bathyal/abyssal sediments. Our data indicate that the decomposition of
viruses provides an important, previously ignored contribution to deep-sea
ecosystem functioning and has an important role in nutrient cycling within the
largest ecosystem of the biosphere.
PMID- 25848025
TI - Environmental constraints drive the partitioning of the soundscape in fishes.
AB - The underwater environment is more and more being depicted as particularly noisy,
and the inventory of calling fishes is continuously increasing. However, it
currently remains unknown how species share the soundscape and are able to
communicate without misinterpreting the messages. Different mechanisms of
interference avoidance have been documented in birds, mammals, and frogs, but
little is known about interference avoidance in fishes. How fish thus partition
the soundscape underwater remains unknown, as acoustic communication and its
organization have never been studied at the level of fish communities. In this
study, passive acoustic recordings were used to inventory sounds produced in a
fish community (120 m depth) in an attempt to understand how different species
partition the acoustic environment. We uncovered an important diversity of fish
sounds, and 16 of the 37 different sounds recorded were sufficiently abundant to
use in a quantitative analysis. We show that sonic activity allows a clear
distinction between a diurnal and a nocturnal group of fishes. Moreover,
frequencies of signals made during the day overlap, whereas there is a clear
distinction between the different representatives of the nocturnal callers
because of a lack of overlap in sound frequency. This first demonstration, to our
knowledge, of interference avoidance in a fish community can be understood by the
way sounds are used. In diurnal species, sounds are mostly used to support visual
display, whereas nocturnal species are generally deprived of visual cues,
resulting in acoustic constraints being more important.
PMID- 25848026
TI - Sorting the wheat from the chaff in dopamine neuron-based cell therapies.
PMID- 25848027
TI - In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP
PET brain imaging.
AB - Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a
variety of cognitive, behavioral, and motor symptoms linked to cumulative brain
damage sustained from single, episodic, or repetitive traumatic brain injury
(TBI). No definitive clinical diagnosis for this condition exists. In this work,
we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution
in retired professional American football players with suspected CTE (n = 14) and
compared results with those of cognitively intact controls (n = 28) and patients
with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively
associated with CTE. [F-18]FDDNP PET imaging results in the retired players
suggested the presence of neuropathological patterns consistent with models of
concussion wherein brainstem white matter tracts undergo early axonal damage and
cumulative axonal injuries along subcortical, limbic, and cortical brain
circuitries supporting mood, emotions, and behavior. This deposition pattern is
distinctively different from the progressive pattern of neuropathology [paired
helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins in the
medial temporal lobe progressing along the cortical default mode network, with no
or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET
imaging pattern in cases of suspected CTE also is primarily consistent with PHF
tau distribution observed at autopsy in subjects with a history of mild TBI and
autopsy-confirmed diagnosis of CTE.
PMID- 25848028
TI - fMRI of the rod scotoma elucidates cortical rod pathways and implications for
lesion measurements.
AB - Are silencing, ectopic shifts, and receptive field (RF) scaling in cortical
scotoma projection zones (SPZs) the result of long-term reorganization
(plasticity) or short-term adaptation? Electrophysiological studies of SPZs after
retinal lesions in animal models remain controversial, because they are unable to
conclusively answer this question because of limitations of the methodology.
Here, we used functional MRI (fMRI) visual field mapping through population RF
(pRF) modeling with moving bar stimuli under photopic and scotopic conditions to
measure the effects of the rod scotoma in human early visual cortex. As a
naturally occurring central scotoma, it has a large cortical representation, is
free of traumatic lesion complications, is completely reversible, and has not
reorganized under normal conditions (but can as seen in rod monochromats). We
found that the pRFs overlapping the SPZ in V1, V2, V3, hV4, and VO-1 generally
(i) reduced their blood oxygen level-dependent signal coherence and (ii) shifted
their pRFs more eccentric but (iii) scaled their pRF sizes in variable ways.
Thus, silencing, ectopic shifts, and pRF scaling in SPZs are not unique
identifiers of cortical reorganization; rather, they can be the expected result
of short-term adaptation. However, are there differences between rod and cone
signals in V1, V2, V3, hV4, and VO-1? We did not find differences for all five
maps in more peripheral eccentricities outside of rod scotoma influence in
coherence, eccentricity representation, or pRF size. Thus, rod and cone signals
seem to be processed similarly in cortex.
PMID- 25848029
TI - Panoramic view of a superfamily of phosphatases through substrate profiling.
AB - Large-scale activity profiling of enzyme superfamilies provides information about
cellular functions as well as the intrinsic binding capabilities of conserved
folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase
superfamily (HADSF) was revealed by screening a customized substrate library
against >200 enzymes from representative prokaryotic species, enabling inferred
annotation of ~35% of the HADSF. An extremely high level of substrate ambiguity
was revealed, with the majority of HADSF enzymes using more than five substrates.
Substrate profiling allowed assignment of function to previously unannotated
enzymes with known structure, uncovered potential new pathways, and identified
iso-functional orthologs from evolutionarily distant taxonomic groups.
Intriguingly, the HADSF subfamily having the least structural elaboration of the
Rossmann fold catalytic domain was the most specific, consistent with the concept
that domain insertions drive the evolution of new functions and that the broad
specificity observed in HADSF may be a relic of this process.
PMID- 25848030
TI - Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue
development.
AB - Although recent studies have shown that brown adipose tissue (BAT) arises from
progenitor cells that also give rise to skeletal muscle, the developmental
signals that control the formation of BAT remain largely unknown. Here, we show
that brown preadipocytes possess primary cilia and can respond to Hedgehog (Hh)
signaling. Furthermore, cell-autonomous activation of Hh signaling blocks early
brown-preadipocyte differentiation, inhibits BAT formation in vivo, and results
in replacement of neck BAT with poorly differentiated skeletal muscle. Finally,
we show that Hh signaling inhibits BAT formation partially through up-regulation
of chicken ovalbumin upstream promoter transcription factor II (COUP-TFII). Taken
together, our studies uncover a previously unidentified role for Hh as an
inhibitor of BAT development.
PMID- 25848031
TI - Adaptive evolution toward larger size in mammals.
AB - The notion that large body size confers some intrinsic advantage to biological
species has been debated for centuries. Using a phylogenetic statistical approach
that allows the rate of body size evolution to vary across a phylogeny, we find a
long-term directional bias toward increasing size in the mammals. This pattern
holds separately in 10 of 11 orders for which sufficient data are available and
arises from a tendency for accelerated rates of evolution to produce increases,
but not decreases, in size. On a branch-by-branch basis, increases in body size
have been more than twice as likely as decreases, yielding what amounts to
millions and millions of years of rapid and repeated increases in size away from
the small ancestral mammal. These results are the first evidence, to our
knowledge, from extant species that are compatible with Cope's rule: the pattern
of body size increase through time observed in the mammalian fossil record. We
show that this pattern is unlikely to be explained by several nonadaptive
mechanisms for increasing size and most likely represents repeated responses to
new selective circumstances. By demonstrating that it is possible to uncover
ancient evolutionary trends from a combination of a phylogeny and appropriate
statistical models, we illustrate how data from extant species can complement
paleontological accounts of evolutionary history, opening up new avenues of
investigation for both.
PMID- 25848032
TI - Identity-specific coding of future rewards in the human orbitofrontal cortex.
AB - Nervous systems must encode information about the identity of expected outcomes
to make adaptive decisions. However, the neural mechanisms underlying identity
specific value signaling remain poorly understood. By manipulating the value and
identity of appetizing food odors in a pattern-based imaging paradigm of human
classical conditioning, we were able to identify dissociable predictive
representations of identity-specific reward in orbitofrontal cortex (OFC) and
identity-general reward in ventromedial prefrontal cortex (vmPFC). Reward-related
functional coupling between OFC and olfactory (piriform) cortex and between vmPFC
and amygdala revealed parallel pathways that support identity-specific and
general predictive signaling. The demonstration of identity-specific value
representations in OFC highlights a role for this region in model-based behavior
and reveals mechanisms by which appetitive behavior can go awry.
PMID- 25848033
TI - Sterile inflammation in the spleen during atherosclerosis provides oxidation
specific epitopes that induce a protective B-cell response.
AB - The B-cell response in atherosclerosis is directed toward oxidation-specific
epitopes such as phosphorylcholine (PC) that arise during disease-driven
oxidation of self-antigens. PC-bearing antigens have been used to induce
atheroprotective antibodies against modified low-density lipoproteins (oxLDL),
leading to plaque reduction. Previous studies have found that B-cell transfer
from aged atherosclerotic mice confers protection to young mice, but the
mechanism is unknown. Here, we dissected the atheroprotective response in the
spleen and found an ongoing germinal center reaction, accumulation of antibody
forming cells, and inflammasome activation in apolipoprotein E-deficient mice
(Apoe(-/-)). Specific B-cell clone expansion involved the heavy chain variable
region (Vh) 5 and Vh7 B-cell receptor families that harbor anti-PC reactivity.
oxLDL also accumulated in the spleen. To investigate whether protection could be
induced by self-antigens alone, we injected apoptotic cells that carry the same
oxidation-specific epitopes as oxLDL. This treatment reduced serum cholesterol
and inhibited the development of atherosclerosis in a B-cell-dependent manner.
Thus, we conclude that the spleen harbors a protective B-cell response that is
initiated in atherosclerosis through sterile inflammation. These data highlight
the importance of the spleen in atherosclerosis-associated immunity.
PMID- 25848034
TI - Alternative approach to protein structure prediction based on sequential
similarity of physical properties.
AB - The relationship between protein sequence and structure arises entirely from
amino acid physical properties. An alternative method is therefore proposed to
identify homologs in which residue equivalence is based exclusively on the
pairwise physical property similarities of sequences. This approach, the property
factor method (PFM), is entirely different from those in current use. A
comparison is made between our method and PSI BLAST. We demonstrate that
traditionally defined sequence similarity can be very low for pairs of sequences
(which therefore cannot be identified using PSI BLAST), but similarity of
physical property distributions results in almost identical 3D structures. The
performance of PFM is shown to be better than that of PSI BLAST when sequence
matching is comparable, based on a comparison using targets from CASP10 (89
targets) and CASP11 (51 targets). It is also shown that PFM outperforms PSI BLAST
in informatically challenging targets.
PMID- 25848036
TI - Profile of Melinda a. Zeder.
PMID- 25848035
TI - Base-enhanced catalytic water oxidation by a carboxylate-bipyridine Ru(II)
complex.
AB - In aqueous solution above pH 2.4 with 4% (vol/vol) CH3CN, the complex
[Ru(II)(bda)(isoq)2] (bda is 2,2'-bipyridine-6,6'-dicarboxylate; isoq is
isoquinoline) exists as the open-arm chelate, [Ru(II)(CO2-bpy-CO2(
))(isoq)2(NCCH3)], as shown by (1)H and (13)C-NMR, X-ray crystallography, and pH
titrations. Rates of water oxidation with the open-arm chelate are remarkably
enhanced by added proton acceptor bases, as measured by cyclic voltammetry (CV).
In 1.0 M PO4(3-), the calculated half-time for water oxidation is ~7 MUs. The key
to the rate accelerations with added bases is direct involvement of the buffer
base in either atom-proton transfer (APT) or concerted electron-proton transfer
(EPT) pathways.
PMID- 25848037
TI - Architecture of the cerebral cortical association connectome underlying
cognition.
AB - Cognition presumably emerges from neural activity in the network of association
connections between cortical regions that is modulated by inputs from sensory and
state systems and directs voluntary behavior by outputs to the motor system. To
reveal global architectural features of the cortical association connectome,
network analysis was performed on >16,000 reports of histologically defined
axonal connections between cortical regions in rat. The network analysis reveals
an organization into four asymmetrically interconnected modules involving the
entire cortex in a topographic and topologic core-shell arrangement. There is
also a topographically continuous U-shaped band of cortical areas that are highly
connected with each other as well as with the rest of the cortex extending
through all four modules, with the temporal pole of this band (entorhinal area)
having the most cortical association connections of all. These results provide a
starting point for compiling a mammalian nervous system connectome that could
ultimately reveal novel correlations between genome-wide association studies and
connectome-wide association studies, leading to new insights into the cellular
architecture supporting cognition.
PMID- 25848038
TI - Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade.
AB - We have generated low-expressing and high-expressing endothelin-1 genes (L and H)
and have bred mice with four levels of expression: L/L, ~20%; L/+, ~65%; +/+
(wild type), 100%; and H/+, ~350%. The hypomorphic L allele can be
spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination.
Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and
increased plasma volumes, together with increased ventricular superoxide levels,
increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular
stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff
hearts. Global or cardiomyocyte-specific switching expression from L to H
normalized the abnormalities already present in young adult L/L mice. An
epithelial sodium channel antagonist normalized plasma volume and blood pressure,
but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic
made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially
improved cardiac function. Genetic absence of Mmp9 also improved cardiac
function, but increased superoxide remained. We conclude that endothelin-1 is
critical for maintaining normal contractile function, for controlling superoxide
and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to
prevent overstretching. Even a modest (~35%) decrease in endothelin-1 gene (Edn1)
expression is sufficient to cause cardiac dysfunction.
PMID- 25848039
TI - Acoustic separation of circulating tumor cells.
AB - Circulating tumor cells (CTCs) are important targets for cancer biology studies.
To further elucidate the role of CTCs in cancer metastasis and prognosis,
effective methods for isolating extremely rare tumor cells from peripheral blood
must be developed. Acoustic-based methods, which are known to preserve the
integrity, functionality, and viability of biological cells using label-free and
contact-free sorting, have thus far not been successfully developed to isolate
rare CTCs using clinical samples from cancer patients owing to technical
constraints, insufficient throughput, and lack of long-term device stability. In
this work, we demonstrate the development of an acoustic-based microfluidic
device that is capable of high-throughput separation of CTCs from peripheral
blood samples obtained from cancer patients. Our method uses tilted-angle
standing surface acoustic waves. Parametric numerical simulations were performed
to design optimum device geometry, tilt angle, and cell throughput that is more
than 20 times higher than previously possible for such devices. We first
validated the capability of this device by successfully separating low
concentrations (~100 cells/mL) of a variety of cancer cells from cell culture
lines from WBCs with a recovery rate better than 83%. We then demonstrated the
isolation of CTCs in blood samples obtained from patients with breast cancer. Our
acoustic-based separation method thus offers the potential to serve as an
invaluable supplemental tool in cancer research, diagnostics, drug efficacy
assessment, and therapeutics owing to its excellent biocompatibility, simple
design, and label-free automated operation while offering the capability to
isolate rare CTCs in a viable state.
PMID- 25848040
TI - Ovary ecdysteroidogenic hormone requires a receptor tyrosine kinase to activate
egg formation in the mosquito Aedes aegypti.
AB - Mosquitoes are major disease vectors because most species must feed on blood from
a vertebrate host to produce eggs. Blood feeding by the vector mosquito Aedes
aegypti triggers the release of two neurohormones, ovary ecdysteroidogenic
hormone (OEH) and insulin-like peptides (ILPs), which activate multiple processes
required for egg formation. ILPs function by binding to the insulin receptor,
which activates downstream components in the canonical insulin signaling pathway.
OEH in contrast belongs to a neuropeptide family called neuroparsins, whose
receptor is unknown. Here we demonstrate that a previously orphanized receptor
tyrosine kinase (RTK) from A. aegypti encoded by the gene AAEL001915 is an OEH
receptor. Phylogenetic studies indicated that the protein encoded by this gene,
designated AAEL001915, belongs to a clade of RTKs related to the insulin
receptor, which are distinguished by an extracellular Venus flytrap module.
Knockdown of AAEL001915 by RNAi disabled OEH-mediated egg formation in A.
aegypti. AAEL001915 was primarily detected in the mosquito ovary in association
with follicular epithelial cells. Both monomeric and dimeric AAEL001915 were
detected in mosquito ovaries and transfected Drosophila S2 cells. Functional
assays further indicated that OEH bound to dimeric AAEL001915, which resulted in
downstream phosphorylation of Ak strain transforming factor (Akt). We hypothesize
that orthologs of AAEL001915 in other insects are neuroparsin receptors.
PMID- 25848041
TI - Effect of neighborhood stigma on economic transactions.
AB - The hypothesis of neighborhood stigma predicts that individuals who reside in
areas known for high crime, poverty, disorder, and/or racial isolation embody the
negative characteristics attributed to their communities and experience suspicion
and mistrust in their interactions with strangers. This article provides an
experimental test of whether neighborhood stigma affects individuals in one
domain of social life: economic transactions. To evaluate the neighborhood stigma
hypothesis, this study adopts an audit design in a locally organized, online
classified market, using advertisements for used iPhones and randomly
manipulating the neighborhood of the seller. The primary outcome under study is
the number of responses generated by sellers from disadvantaged relative to
advantaged neighborhoods. Advertisements from disadvantaged neighborhoods
received significantly fewer responses than advertisements from advantaged
neighborhoods. Results provide robust evidence that individuals from
disadvantaged neighborhoods bear a stigma that influences their prospects in
economic exchanges. The stigma is greater for advertisements originating from
disadvantaged neighborhoods where the majority of residents are black. This
evidence reveals that residence in a disadvantaged neighborhood not only affects
individuals through mechanisms involving economic resources, institutional
quality, and social networks but also affects residents through the perceptions
of others.
PMID- 25848043
TI - Metallic lead nanospheres discovered in ancient zircons.
AB - Zircon (ZrSiO4) is the most commonly used geochronometer, preserving age and
geochemical information through a wide range of geological processes. However,
zircon U-Pb geochronology can be affected by redistribution of radiogenic Pb,
which is incompatible in the crystal structure. This phenomenon is particularly
common in zircon that has experienced ultra-high temperature metamorphism, where
ion imaging has revealed submicrometer domains that are sufficiently
heterogeneously distributed to severely perturb ages, in some cases yielding
apparent Hadean (>4 Ga) ages from younger zircons. Documenting the composition
and mineralogy of these Pb-enriched domains is essential for understanding the
processes of Pb redistribution in zircon and its effects on geochronology. Using
high-resolution scanning transmission electron microscopy, we show that Pb-rich
domains previously identified in zircons from East Antarctic granulites are 5-30
nm nanospheres of metallic Pb. They are randomly distributed with respect to
zircon crystallinity, and their association with a Ti- and Al-rich silica melt
suggests that they represent melt inclusions generated during ultra-high
temperature metamorphism. Metallic Pb is exceedingly rare in nature and
previously has not been reported in association with high-grade metamorphism.
Formation of these metallic nanospheres within annealed zircon effectively halts
the loss of radiogenic Pb from zircon. Both the redistribution and phase
separation of radiogenic Pb in this manner can compromise the precision and
accuracy of U-Pb ages obtained by high spatial resolution methods.
PMID- 25848042
TI - Balance between cell-substrate adhesion and myosin contraction determines the
frequency of motility initiation in fish keratocytes.
AB - Cells are dynamic systems capable of spontaneously switching among stable states.
One striking example of this is spontaneous symmetry breaking and motility
initiation in fish epithelial keratocytes. Although the biochemical and
mechanical mechanisms that control steady-state migration in these cells have
been well characterized, the mechanisms underlying symmetry breaking are less
well understood. In this work, we have combined experimental manipulations of
cell-substrate adhesion strength and myosin activity, traction force
measurements, and mathematical modeling to develop a comprehensive mechanical
model for symmetry breaking and motility initiation in fish epithelial
keratocytes. Our results suggest that stochastic fluctuations in adhesion
strength and myosin localization drive actin network flow rates in the
prospective cell rear above a critical threshold. Above this threshold, high
actin flow rates induce a nonlinear switch in adhesion strength, locally
switching adhesions from gripping to slipping and further accelerating actin flow
in the prospective cell rear, resulting in rear retraction and motility
initiation. We further show, both experimentally and with model simulations, that
the global levels of adhesion strength and myosin activity control the stability
of the stationary state: The frequency of symmetry breaking decreases with
increasing adhesion strength and increases with increasing myosin contraction.
Thus, the relative strengths of two opposing mechanical forces--contractility and
cell-substrate adhesion--determine the likelihood of spontaneous symmetry
breaking and motility initiation.
PMID- 25848044
TI - Stoichiometric control of DNA-grafted colloid self-assembly.
AB - There has been considerable interest in understanding the self-assembly of DNA
grafted nanoparticles into different crystal structures, e.g., CsCl, AlB2, and
Cr3Si. Although there are important exceptions, a generally accepted view is that
the right stoichiometry of the two building block colloids needs to be mixed to
form the desired crystal structure. To incisively probe this issue, we combine
experiments and theory on a series of DNA-grafted nanoparticles at varying
stoichiometries, including noninteger values. We show that stoichiometry can
couple with the geometries of the building blocks to tune the resulting
equilibrium crystal morphology. As a concrete example, a stoichiometric ratio of
3:1 typically results in the Cr3Si structure. However, AlB2 can form when
appropriate building blocks are used so that the AlB2 standard-state free energy
is low enough to overcome the entropic preference for Cr3Si. These situations can
also lead to an undesirable phase coexistence between crystal polymorphs. Thus,
whereas stoichiometry can be a powerful handle for direct control of lattice
formation, care must be taken in its design and selection to avoid polymorph
coexistence.
PMID- 25848045
TI - Small molecule-induced oxidation of protein disulfide isomerase is
neuroprotective.
AB - Protein disulfide isomerase (PDI) is a chaperone protein in the endoplasmic
reticulum that is up-regulated in mouse models of, and brains of patients with,
neurodegenerative diseases involving protein misfolding. PDI's role in these
diseases, however, is not fully understood. Here, we report the discovery of a
reversible, neuroprotective lead optimized compound (LOC)14, that acts as a
modulator of PDI. LOC14 was identified using a high-throughput screen of ~10,000
lead-optimized compounds for potent rescue of viability of PC12 cells expressing
mutant huntingtin protein, followed by an evaluation of compounds on PDI
reductase activity in an in vitro screen. Isothermal titration calorimetry and
fluorescence experiments revealed that binding to PDI was reversible with a Kd of
62 nM, suggesting LOC14 to be the most potent PDI inhibitor reported to date.
Using 2D heteronuclear single quantum correlation NMR experiments, we were able
to map the binding site of LOC14 as being adjacent to the active site and to
observe that binding of LOC14 forces PDI to adopt an oxidized conformation.
Furthermore, we found that LOC14-induced oxidation of PDI has a neuroprotective
effect not only in cell culture, but also in corticostriatal brain slice
cultures. LOC14 exhibited high stability in mouse liver microsomes and blood
plasma, low intrinsic microsome clearance, and low plasma-protein binding. These
results suggest that LOC14 is a promising lead compound to evaluate the potential
therapeutic effects of modulating PDI in animal models of disease.
PMID- 25848046
TI - Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and
population subsistence strategy.
AB - The dietary change resulting from the domestication of plant and animal species
and development of agriculture at different locations across the world was one of
the most significant changes in human evolution. An increase in dietary
carbohydrates caused an increase in dental caries following the development of
agriculture, mediated by the cariogenic oral bacterium Streptococcus mutans.
Salivary agglutinin [SAG, encoded by the deleted in malignant brain tumors 1
(DMBT1) gene] is an innate immune receptor glycoprotein that binds a variety of
bacteria and viruses, and mediates attachment of S. mutans to hydroxyapatite on
the surface of the tooth. In this study we show that multiallelic copy number
variation (CNV) within DMBT1 is extensive across all populations and is predicted
to result in between 7-20 scavenger-receptor cysteine-rich (SRCR) domains within
each SAG molecule. Direct observation of de novo mutation in multigeneration
families suggests these CNVs have a very high mutation rate for a protein-coding
locus, with a mutation rate of up to 5% per gamete. Given that the SRCR domains
bind S. mutans and hydroxyapatite in the tooth, we investigated the association
of sequence diversity at the SAG-binding gene of S. mutans, and DMBT1 CNV.
Furthermore, we show that DMBT1 CNV is also associated with a history of
agriculture across global populations, suggesting that dietary change as a result
of agriculture has shaped the pattern of CNV at DMBT1, and that the DMBT1-S.
mutans interaction is a promising model of host-pathogen-culture coevolution in
humans.
PMID- 25848047
TI - Compromised peroxisomes in idiopathic pulmonary fibrosis, a vicious cycle
inducing a higher fibrotic response via TGF-beta signaling.
AB - Idiopathic pulmonary fibrosis (IPF) is a devastating disease, and its pathogenic
mechanisms remain incompletely understood. Peroxisomes are known to be important
in ROS and proinflammatory lipid degradation, and their deficiency induces liver
fibrosis. However, altered peroxisome functions in IPF pathogenesis have never
been investigated. By comparing peroxisome-related protein and gene expression in
lung tissue and isolated lung fibroblasts between human control and IPF patients,
we found that IPF lungs exhibited a significant down-regulation of peroxisomal
biogenesis and metabolism (e.g., PEX13p and acyl-CoA oxidase 1). Moreover, in
vivo the bleomycin-induced down-regulation of peroxisomes was abrogated in
transforming growth factor beta (TGF-beta) receptor II knockout mice indicating a
role for TGF-beta signaling in the regulation of peroxisomes. Furthermore, in
vitro treatment of IPF fibroblasts with the profibrotic factors TGF-beta1 or
tumor necrosis factor alpha (TNF-alpha) was found to down-regulate peroxisomes
via the AP-1 signaling pathway. Therefore, the molecular mechanisms by which
reduced peroxisomal functions contribute to enhanced fibrosis were further
studied. Direct down-regulation of PEX13 by RNAi induced the activation of Smad
dependent TGF-beta signaling accompanied by increased ROS production and resulted
in the release of cytokines (e.g., IL-6, TGF-beta) and excessive production of
collagen I and III. In contrast, treatment of fibroblasts with ciprofibrate or
WY14643, PPAR-alpha activators, led to peroxisome proliferation and reduced the
TGF-beta-induced myofibroblast differentiation and collagen protein in IPF cells.
Taken together, our findings suggest that compromised peroxisome activity might
play an important role in the molecular pathogenesis of IPF and fibrosis
progression, possibly by exacerbating pulmonary inflammation and intensifying the
fibrotic response in the patients.
PMID- 25848048
TI - Continental-level biodiversity collapse.
PMID- 25848049
TI - Stochastic induction of persister cells by HipA through (p)ppGpp-mediated
activation of mRNA endonucleases.
AB - The model organism Escherichia coli codes for at least 11 type II toxin-antitoxin
(TA) modules, all implicated in bacterial persistence (multidrug tolerance). Ten
of these encode messenger RNA endonucleases (mRNases) inhibiting translation by
catalytic degradation of mRNA, and the 11th module, hipBA, encodes HipA (high
persister protein A) kinase, which inhibits glutamyl tRNA synthetase (GltX). In
turn, inhibition of GltX inhibits translation and induces the stringent response
and persistence. Previously, we presented strong support for a model proposing
(p)ppGpp (guanosine tetra and penta-phosphate) as the master regulator of
persistence. Stochastic variation of [(p)ppGpp] in single cells induced TA
encoded mRNases via a pathway involving polyphosphate and Lon protease.
Polyphosphate activated Lon to degrade all known type II antitoxins of E. coli.
In turn, the activated mRNases induced persistence and multidrug tolerance.
However, even though it was known that activation of HipA stimulated (p)ppGpp
synthesis, our model did not explain how hipBA induced persistence. Here we show
that, in support of and consistent with our initial model, HipA-induced
persistence depends not only on (p)ppGpp but also on the 10 mRNase-encoding TA
modules, Lon protease, and polyphosphate. Importantly, observations with single
cells convincingly show that the high level of (p)ppGpp caused by activation of
HipA does not induce persistence in the absence of TA-encoded mRNases. Thus, slow
growth per se does not induce persistence in the absence of TA-encoded toxins,
placing these genes as central effectors of bacterial persistence.
PMID- 25848050
TI - Information flow between interacting human brains: Identification, validation,
and relationship to social expertise.
AB - Social interactions are fundamental for human behavior, but the quantification of
their neural underpinnings remains challenging. Here, we used hyperscanning
functional MRI (fMRI) to study information flow between brains of human dyads
during real-time social interaction in a joint attention paradigm. In a hardware
setup enabling immersive audiovisual interaction of subjects in linked fMRI
scanners, we characterize cross-brain connectivity components that are unique to
interacting individuals, identifying information flow between the sender's and
receiver's temporoparietal junction. We replicate these findings in an
independent sample and validate our methods by demonstrating that cross-brain
connectivity relates to a key real-world measure of social behavior. Together,
our findings support a central role of human-specific cortical areas in the brain
dynamics of dyadic interactions and provide an approach for the noninvasive
examination of the neural basis of healthy and disturbed human social behavior
with minimal a priori assumptions.
PMID- 25848051
TI - Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in
sensory neurons.
AB - The capsaicin receptor transient receptor potential cation channel vanilloid 1
(TRPV1) is activated by various noxious stimuli, and the stimuli are converted
into electrical signals in primary sensory neurons. It is believed that cation
influx through TRPV1 causes depolarization, leading to the activation of voltage
gated sodium channels, followed by the generation of action potential. Here we
report that the capsaicin-evoked action potential could be induced by two
components: a cation influx-mediated depolarization caused by TRPV1 activation
and a subsequent anion efflux-mediated depolarization via activation of anoctamin
1 (ANO1), a calcium-activated chloride channel, resulting from the entry of
calcium through TRPV1. The interaction between TRPV1 and ANO1 is based on their
physical binding. Capsaicin activated the chloride currents in an extracellular
calcium-dependent manner in HEK293T cells expressing TRPV1 and ANO1. Similarly,
in mouse dorsal root ganglion neurons, capsaicin-activated inward currents were
inhibited significantly by a specific ANO1 antagonist, T16Ainh-A01 (A01), in the
presence of a high concentration of EGTA but not in the presence of BAPTA [1,2
bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid]. The generation of a
capsaicin-evoked action potential also was inhibited by A01. Furthermore, pain
related behaviors in mice treated with capsaicin, but not with alphabeta
methylene ATP, were reduced significantly by the concomitant administration of
A01. These results indicate that TRPV1-ANO1 interaction is a significant pain
enhancing mechanism in the peripheral nervous system.
PMID- 25848052
TI - FtsZ filament capping by MciZ, a developmental regulator of bacterial division.
AB - Cytoskeletal structures are dynamically remodeled with the aid of regulatory
proteins. FtsZ (filamentation temperature-sensitive Z) is the bacterial homolog
of tubulin that polymerizes into rings localized to cell-division sites, and the
constriction of these rings drives cytokinesis. Here we investigate the mechanism
by which the Bacillus subtilis cell-division inhibitor, MciZ (mother cell
inhibitor of FtsZ), blocks assembly of FtsZ. The X-ray crystal structure reveals
that MciZ binds to the C-terminal polymerization interface of FtsZ, the
equivalent of the minus end of tubulin. Using in vivo and in vitro assays and
microscopy, we show that MciZ, at substoichiometric levels to FtsZ, causes
shortening of protofilaments and blocks the assembly of higher-order FtsZ
structures. The findings demonstrate an unanticipated capping-based regulatory
mechanism for FtsZ.
PMID- 25848053
TI - General and condition-specific essential functions of Pseudomonas aeruginosa.
AB - The essential functions of a bacterial pathogen reflect the most basic processes
required for its viability and growth, and represent potential therapeutic
targets. Most screens for essential genes have assayed a single condition--growth
in a rich undefined medium--and thus have not distinguished genes that are
generally essential from those that are specific to this particular condition. To
help define these classes for Pseudomonas aeruginosa, we identified genes
required for growth on six different media, including a medium made from cystic
fibrosis patient sputum. The analysis used the Tn-seq circle method to achieve
high genome coverage and analyzed more than 1,000,000 unique insertion positions
(an average of one insertion every 6.0 bp). We identified 352 general and 199
condition-specific essential genes. A subset of assignments was verified in
individual strains with regulated expression alleles. The profile of essential
genes revealed that, compared with Escherichia coli, P. aeruginosa is highly
vulnerable to mutations disrupting central carbon-energy metabolism and reactive
oxygen defenses. These vulnerabilities may arise from the stripped-down
architecture of the organism's carbohydrate utilization pathways and its reliance
on respiration for energy generation. The essential function profile thus
provides fundamental insights into P. aeruginosa physiology as well as
identifying candidate targets for new antibacterial agents.
PMID- 25848054
TI - Productive mRNA stem loop-mediated transcriptional slippage: Crucial features in
common with intrinsic terminators.
AB - Escherichia coli and yeast DNA-dependent RNA polymerases are shown to mediate
efficient nascent transcript stem loop formation-dependent RNA-DNA hybrid
realignment. The realignment was discovered on the heteropolymeric sequence T5C5
and yields transcripts lacking a C residue within a corresponding U5C4. The
sequence studied is derived from a Roseiflexus insertion sequence (IS) element
where the resulting transcriptional slippage is required for transposase
synthesis. The stability of the RNA structure, the proximity of the stem loop to
the slippage site, the length and composition of the slippage site motif, and the
identity of its 3' adjacent nucleotides (nt) are crucial for transcripts lacking
a single C. In many respects, the RNA structure requirements for this slippage
resemble those for hairpin-dependent transcription termination. In a purified in
vitro system, the slippage efficiency ranges from 5% to 75% depending on the
concentration ratios of the nucleotides specified by the slippage sequence and
the 3' nt context. The only previous proposal of stem loop mediated slippage,
which was in Ebola virus expression, was based on incorrect data interpretation.
We propose a mechanical slippage model involving the RNAP translocation state as
the main motor in slippage directionality and efficiency. It is distinct from
previously described models, including the one proposed for paramyxovirus, where
following random movement efficiency is mainly dependent on the stability of the
new realigned hybrid. In broadening the scope for utilization of transcription
slippage for gene expression, the stimulatory structure provides parallels with
programmed ribosomal frameshifting at the translation level.
PMID- 25848055
TI - Sall4-Gli3 system in early limb progenitors is essential for the development of
limb skeletal elements.
AB - Limb skeletal elements originate from the limb progenitor cells, which undergo
expansion and patterning to develop each skeletal element. Posterior-distal
skeletal elements, such as the ulna/fibula and posterior digits develop in a
Sonic hedgehog (Shh)-dependent manner. However, it is poorly understood how
anterior-proximal elements, such as the humerus/femur, the radius/tibia and the
anterior digits, are developed. Here we show that the zinc finger factors Sall4
and Gli3 cooperate for proper development of the anterior-proximal skeletal
elements and also function upstream of Shh-dependent posterior skeletal element
development. Conditional inactivation of Sall4 in the mesoderm before limb
outgrowth caused severe defects in the anterior-proximal skeletal elements in the
hindlimb. We found that Gli3 expression is reduced in Sall4 mutant hindlimbs, but
not in forelimbs. This reduction caused posteriorization of nascent hindlimb
buds, which is correlated with a loss of anterior digits. In proximal
development, Sall4 integrates Gli3 and the Plzf-Hox system, in addition to
proliferative expansion of cells in the mesenchymal core of nascent hindlimb
buds. Whereas forelimbs developed normally in Sall4 mutants, further genetic
analysis identified that the Sall4-Gli3 system is a common regulator of the early
limb progenitor cells in both forelimbs and hindlimbs. The Sall4-Gli3 system also
functions upstream of the Shh-expressing ZPA and the Fgf8-expressing AER in fore-
and hindlimbs. Therefore, our study identified a critical role of the Sall4-Gli3
system at the early steps of limb development for proper development of the
appendicular skeletal elements.
PMID- 25848056
TI - NADPH oxidase DUOX1 promotes long-term persistence of oxidative stress after an
exposure to irradiation.
AB - Ionizing radiation (IR) causes not only acute tissue damage, but also late
effects in several cell generations after the initial exposure. The thyroid gland
is one of the most sensitive organs to the carcinogenic effects of IR, and we
have recently highlighted that an oxidative stress is responsible for the
chromosomal rearrangements found in radio-induced papillary thyroid carcinoma.
Using both a human thyroid cell line and primary thyrocytes, we investigated the
mechanism by which IR induces the generation of reactive oxygen species (ROS)
several days after irradiation. We focused on NADPH oxidases, which are
specialized ROS-generating enzymes known as NOX/DUOX. Our results show that IR
induces delayed NADPH oxidase DUOX1-dependent H2O2 production in a dose-dependent
manner, which is sustained for several days. We report that p38 MAPK, activated
after IR, increased DUOX1 via IL-13 expression, leading to persistent DNA damage
and growth arrest. Pretreatment of cells with catalase, a scavenger of H2O2, or
DUOX1 down-regulation by siRNA abrogated IR-induced DNA damage. Analysis of human
thyroid tissues showed that DUOX1 is elevated not only in human radio-induced
thyroid tumors, but also in sporadic thyroid tumors. Taken together, our data
reveal a key role of DUOX1-dependent H2O2 production in long-term persistent
radio-induced DNA damage. Our data also show that DUOX1-dependent H2O2
production, which induces DNA double-strand breaks, can cause genomic instability
and promote the generation of neoplastic cells through its mutagenic effect.
PMID- 25848057
TI - Visualized macrophage dynamics and significance of S100A8 in obese fat.
AB - Chronic low-grade inflammation of adipose tissue plays a crucial role in the
pathophysiology of obesity. Immunohistological microscopic analysis in obese fat
tissue has demonstrated the infiltration of several immune cells such as
macrophages, but dynamics of immune cells have not been fully elucidated and
clarified. Here, by using intravital multiphoton imaging technique, to our
knowledge for the first time, we analyzed and visualized the inflammatory
processes in adipose tissue under high-fat and high-sucrose (HF/HS) diet with
lysozyme M-EGFP transgenic (LysM(EGFP)) mice whose EGFP was specifically
expressed in the myelomonocytic lineage. Mobility of LysM(EGFP)-positive
macrophages was shown to be activated just 5 d after HF/HS diet, when the
distinct hypertrophy of adipocytes and the accumulation of macrophages still have
not become prominent. Significant increase of S100A8 was detected in mature
adipocyte fraction just 5 d after HF/HS diet. Recombinant S100A8 protein
stimulated chemotactic migration in vitro and in vivo, as well as induced
proinflammatory molecules, both macrophages and adipocytes, such as TNF-alpha and
chemokine (C-C motif) ligand 2. Finally, an antibody against S100A8 efficiently
suppressed the HF/HS diet-induced initial inflammatory change, i.e., increased
mobilization of adipose LysM(EGFP)-positive macrophages, and ameliorated HF/HS
diet-induced insulin resistance. In conclusion, time-lapse intravital multiphoton
imaging of adipose tissues identified the very early event exhibiting increased
mobility of macrophages, which may be triggered by increased expression of
adipose S100A8 and results in progression of chronic inflammation in situ.
PMID- 25848058
TI - Shapely DNA attracts the right partner.
PMID- 25848060
TI - The human prenatal sex ratio: A major surprise.
PMID- 25848059
TI - Potential role for snoRNAs in PKR activation during metabolic stress.
AB - Protein kinase RNA-activated (PKR) has long been known to be activated by viral
double-stranded RNA (dsRNA) as part of the mammalian immune response. However, in
mice PKR is also activated by metabolic stress in the absence of viral infection,
and this requires a functional kinase domain, as well as a functional dsRNA
binding domain. The endogenous cellular RNA that potentially leads to PKR
activation during metabolic stress is unknown. We investigated this question
using mouse embryonic fibroblast cells expressing wild-type PKR (PKRWT) or PKR
with a point mutation in each dsRNA-binding motif (PKRRM). Using this system, we
identified endogenous RNA that interacts with PKR after induction of metabolic
stress by palmitic acid (PA) treatment. Specifically, RIP-Seq analyses showed
that the majority of enriched RNAs that interacted with WT PKR (>=twofold, false
discovery rate <= 5%) were small nucleolar RNAs (snoRNAs). Immunoprecipitation of
PKR in extracts of UV-cross-linked cells, followed by RT-qPCR, confirmed that
snoRNAs were enriched in PKRWT samples after PA treatment, but not in the PKRRM
samples. We also demonstrated that a subset of identified snoRNAs bind and
activate PKR in vitro; the presence of a 5'-triphosphate enhanced PKR activity
compared with the activity with a 5'-monophosphate, for some, but not all,
snoRNAs. Finally, we demonstrated PKR activation in cells upon snoRNA
transfection, supporting our hypothesis that endogenous snoRNAs can activate PKR.
Our results suggest an unprecedented and unexpected model whereby snoRNAs play a
role in the activation of PKR under metabolic stress.
PMID- 25848061
TI - Female peers in small work groups enhance women's motivation, verbal
participation, and career aspirations in engineering.
AB - For years, public discourse in science education, technology, and policy-making
has focused on the "leaky pipeline" problem: the observation that fewer women
than men enter science, technology, engineering, and mathematics fields and more
women than men leave. Less attention has focused on experimentally testing
solutions to this problem. We report an experiment investigating one solution: we
created "microenvironments" (small groups) in engineering with varying
proportions of women to identify which environment increases motivation and
participation, and whether outcomes depend on students' academic stage. Female
engineering students were randomly assigned to one of three engineering groups of
varying sex composition: 75% women, 50% women, or 25% women. For first-years,
group composition had a large effect: women in female-majority and sex-parity
groups felt less anxious than women in female-minority groups. However, among
advanced students, sex composition had no effect on anxiety. Importantly, group
composition significantly affected verbal participation, regardless of women's
academic seniority: women participated more in female-majority groups than sex
parity or female-minority groups. Additionally, when assigned to female-minority
groups, women who harbored implicit masculine stereotypes about engineering
reported less confidence and engineering career aspirations. However, in sex
parity and female-majority groups, confidence and career aspirations remained
high regardless of implicit stereotypes. These data suggest that creating small
groups with high proportions of women in otherwise male-dominated fields is one
way to keep women engaged and aspiring toward engineering careers. Although sex
parity works sometimes, it is insufficient to boost women's verbal participation
in group work, which often affects learning and mastery.
PMID- 25848062
TI - Probing liquid dynamics, one molecule at a time.
PMID- 25848063
TI - Smaller human population in 2100 could importantly reduce the risk of climate
catastrophe.
PMID- 25848064
TI - Reply to Wilkinson: Minor role of programmed methylation and demethylation in
mammalian development.
PMID- 25848065
TI - Evidence that DNA methylation engenders dynamic gene regulation.
PMID- 25848066
TI - Reply to van de Sandt and Rimmelzwaan: Matching epitope display with functional
avidity.
PMID- 25848067
TI - Immunodominant responses to the influenza virus M158-66 epitope: Stealth or
protection?
PMID- 25848068
TI - Comment on "cutting edge: epigenetic regulation of Foxp3 defines a stable
population of CD4+ regulatory T cells in tumors from mice and humans".
PMID- 25848069
TI - Response to comment on "cutting edge: epigenetic regulation of Foxp3 defines a
stable population of CD4+ regulatory T cells in tumors from mice and humans".
PMID- 25848070
TI - Endothelial actin-binding proteins and actin dynamics in leukocyte
transendothelial migration.
AB - The endothelium is the first barrier that leukocytes have to overcome during
recruitment to sites of inflamed tissues. The leukocyte extravasation cascade is
a complex multistep process that requires the activation of various adhesion
molecules and signaling pathways, as well as actin remodeling, in both leukocytes
and endothelial cells. Endothelial adhesion molecules, such as E-selectin or ICAM
1, are connected to the actin cytoskeleton via actin-binding proteins (ABPs).
Although the contribution of receptor-ligand interactions to leukocyte
extravasation has been studied extensively, the contribution of endothelial ABPs
to the regulation of leukocyte adhesion and transendothelial migration remains
poorly understood. This review focuses on recently published evidence that
endothelial ABPs, such as cortactin, myosin, or alpha-actinin, regulate leukocyte
extravasation by controlling actin dynamics, biomechanical properties of
endothelia, and signaling pathways, such as GTPase activation, during
inflammation. Thus, ABPs may serve as targets for novel treatment strategies for
disorders characterized by excessive leukocyte recruitment.
PMID- 25848071
TI - Is the complement activation product C3a a proinflammatory molecule? Re
evaluating the evidence and the myth.
AB - The complement activation product C3a is often described as a proinflammatory
mediator, alongside its downstream cousin, C5a. However, emerging studies show
that C3a has several anti-inflammatory facets in vivo. For example, in the acute
inflammatory response, C3a acts in direct opposition to C5a, through preventing
the accumulation of neutrophils in inflamed tissues by independently regulating
their mobilization. This acute, protective, and opposing activity of C3a to C5a
is also illustrated in models of septicemia. In this article, we reinvestigate
the discovery and original classification of C3a as a proinflammatory mediator
and highlight the emerging studies demonstrating anti-inflammatory effects for
C3a in the immune response. It is our hope that this review illuminates these
apparently contradictory roles for C3a and challenges the general dogma
surrounding C3a, which, historically, has ubiquitously been described as a
proinflammatory mediator. In light of this, we urge investigators to use
"inflammatory modulator" as the descriptor for C3a.
PMID- 25848072
TI - Comparative effectiveness of autologous blood-derived products, shock-wave
therapy and corticosteroids for treatment of plantar fasciitis: a network meta
analysis.
AB - OBJECTIVE: To compare the efficacy of autologous blood-derived products (ABPs),
CSs and shock-wave (SW) therapy in the treatment of plantar fasciitis. METHODS:
Electronic databases were searched for studies that compared ABPs, CSs and SW
therapy for the treatment of plantar fasciitis, published up to June 2014. The
primary and secondary outcomes were reduction in visual analogue scale (VAS)
score at 3 and 6 months and odds ratio of treatment success, respectively. Groups
were compared by traditional pair-wise meta-analysis and by network meta
analysis. RESULTS: Seven randomized controlled trials and three quasi
experimental studies that included 604 patients were enrolled. Pair-wise meta
analysis indicated a trend favouring ABPs over CSs regarding VAS reduction at 3
months; this benefit was significant in a subgroup analysis of platelet-rich
plasma (PRP) vs CSs. There were no significant between-group differences in VAS
reduction at 6 months and in treatment success. Network meta-analysis showed that
ABPs had the highest probability of being the best treatment at 3 months, but
ABPs were slightly inferior to SW for VAS reduction at 6 months. Although SW
therapy had the highest likelihood of treatment success, the between-group
differences in probabilities were less remarkable than those for pain reduction
at 3 and 6 months. CONCLUSION: ABPs, followed by CSs, were best in providing
relief from pain at 3 months. SW therapy and ABPs had similar probabilities of
providing pain relief at 6 months, and were better than CSs at that time.
Subgroup analysis indicated that an ABP regimen consisting of platelet-rich
plasma improves treatment efficacy.
PMID- 25848073
TI - Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal
Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport.
AB - Kcnj10 encodes the inwardly rectifying K(+) channel Kir4.1 in the basolateral
membrane of the distal convoluted tubule (DCT) and is activated by c-Src.
However, the regulation and function of this K(+) channel are incompletely
characterized. Here, patch-clamp experiments in Kcnj10-transfected HEK293 cells
demonstrated that c-Src-induced stimulation of Kcnj10 requires coexpression of
caveolin-1 (cav-1), and immunostaining showed expression of cav-1 in the
basolateral membrane of parvalbumin-positive DCT. Patch-clamp experiments
detected a 40-pS inwardly rectifying K(+) channel, a heterotetramer of
Kir4.1/Kir5.1, in the basolateral membrane of the early DCT (DCT1) in both wild
type (WT) and cav-1-knockout (KO) mice. However, the activity of this basolateral
40-pS K(+) channel was lower in KO mice than in WT mice. Moreover, the K(+)
reversal potential (an indication of membrane potential) was less negative in the
DCT1 of KO mice than in the DCT1 of WT mice. Western blot analysis demonstrated
that cav-1 deficiency decreased the expression of the Na(+)/Cl(-) cotransporter
and Ste20-proline-alanine-rich kinase (SPAK) but increased the expression of
epithelial Na(+) channel-alpha. Furthermore, the urinary excretion of Mg(2+) and
K(+) was significantly higher in KO mice than in WT mice, and KO mice developed
hypomagnesemia, hypocalcemia, and hypokalemia. We conclude that disruption of cav
1 decreases basolateral K(+) channel activity and depolarizes the cell membrane
potential in the DCT1 at least in part by suppressing the stimulatory effect of c
Src on Kcnj10. Furthermore, the decrease in Kcnj10 and Na(+)/Cl(-) cotransporter
expression induced by cav-1 deficiency may underlie the compromised renal
transport of Mg(2+), Ca(2+), and K(+).
PMID- 25848074
TI - Romantic partner influences on prenatal and postnatal substance use in young
couples.
AB - BACKGROUND: Alcohol, tobacco and other drug use (ATOD) among adolescent and young
adult couples during prenatal and postnatal periods is a significant public
health problem, and couples may mutually influence each others' ATOD behaviors.
PURPOSE: The current study investigated romantic partner influences on ATOD among
adolescent and young adult couples during pregnancy and postnatal periods.
METHODS: Participants were 296 young couples in the second or third trimester of
pregnancy recruited from OBGYN clinics between July 2007 and February 2011.
Participants completed questionnaires at prenatal, 6 months postnatal, and 12
months postnatal periods. Dyadic data analysis was conducted to assess the
stability and interdependence of male and female ATOD over time. RESULTS: Male
partner cigarette and marijuana use in the prenatal period significantly
predicted female cigarette and marijuana use at 6 months postnatal (b = 0.14, P <
0.01; b = 0.11, P < 0.05, respectively). Male partner marijuana use at 6 months
postnatal also significantly predicted female marijuana use at 12 months
postnatal (b = 0.11, P < 0.05). Additionally, significant positive correlations
were found for partner alcohol and marijuana at pre-pregnancy and 6 months
postnatal, and partner cigarette use at pre-pregnancy, 6 months and 12 months
postnatal. CONCLUSIONS: Partner ATOD among young fathers, particularly during the
prenatal period, may play an important role in subsequent ATOD among young
mothers during postnatal periods.
PMID- 25848075
TI - A dynamical model of plasma turbulence in the solar wind.
AB - A dynamical approach, rather than the usual statistical approach, is taken to
explore the physical mechanisms underlying the nonlinear transfer of energy, the
damping of the turbulent fluctuations, and the development of coherent structures
in kinetic plasma turbulence. It is argued that the linear and nonlinear dynamics
of Alfven waves are responsible, at a very fundamental level, for some of the key
qualitative features of plasma turbulence that distinguish it from hydrodynamic
turbulence, including the anisotropic cascade of energy and the development of
current sheets at small scales. The first dynamical model of kinetic turbulence
in the weakly collisional solar wind plasma that combines self-consistently the
physics of Alfven waves with the development of small-scale current sheets is
presented and its physical implications are discussed. This model leads to a
simplified perspective on the nature of turbulence in a weakly collisional
plasma: the nonlinear interactions responsible for the turbulent cascade of
energy and the formation of current sheets are essentially fluid in nature, while
the collisionless damping of the turbulent fluctuations and the energy injection
by kinetic instabilities are essentially kinetic in nature.
PMID- 25848076
TI - Turbulent reconnection and its implications.
AB - Magnetic reconnection is a process of magnetic field topology change, which is
one of the most fundamental processes happening in magnetized plasmas. In most
astrophysical environments, the Reynolds numbers corresponding to plasma flows
are large and therefore the transition to turbulence is inevitable. This
turbulence, which can be pre-existing or driven by magnetic reconnection itself,
must be taken into account for any theory of magnetic reconnection that attempts
to describe the process in the aforementioned environments. This necessity is
obvious as three-dimensional high-resolution numerical simulations show the
transition to the turbulence state of initially laminar reconnecting magnetic
fields. We discuss ideas of how turbulence can modify reconnection with the focus
on the Lazarian & Vishniac (Lazarian & Vishniac 1999 Astrophys. J. 517, 700-718
(doi:10.1086/307233)) reconnection model. We present numerical evidence
supporting the model and demonstrate that it is closely connected to the
experimentally proven concept of Richardson dispersion/diffusion as well as to
more recent advances in understanding of the Lagrangian dynamics of magnetized
fluids. We point out that the generalized Ohm's law that accounts for turbulent
motion predicts the subdominance of the microphysical plasma effects for
reconnection for realistically turbulent media. We show that one of the most
dramatic consequences of turbulence is the violation of the generally accepted
notion of magnetic flux freezing. This notion is a cornerstone of most theories
dealing with magnetized plasmas, and therefore its change induces fundamental
shifts in accepted paradigms, for instance, turbulent reconnection entails
reconnection diffusion process that is essential for understanding star
formation. We argue that at sufficiently high Reynolds numbers the process of
tearing reconnection should transfer to turbulent reconnection. We discuss flares
that are predicted by turbulent reconnection and relate this process to solar
flares and gamma-ray bursts. With reference to experiments, we analyse solar
observations in situ as measurements in the solar wind or heliospheric current
sheet and show the correspondence of data with turbulent reconnection
predictions. Finally, we discuss first-order Fermi acceleration of particles that
is a natural consequence of the turbulent reconnection.
PMID- 25848077
TI - Dissipation and heating in solar wind turbulence: from the macro to the micro and
back again.
AB - The past decade has seen a flurry of research activity focused on discerning the
physics of kinetic scale turbulence in high-speed astrophysical plasma flows. By
'kinetic' we mean spatial scales on the order of or, in particular, smaller than
the ion inertial length or the ion gyro-radius--the spatial scales at which the
ion and electron bulk velocities decouple and considerable change can be seen in
the ion distribution functions. The motivation behind most of these studies is to
find the ultimate fate of the energy cascade of plasma turbulence, and thereby
the channels by which the energy in the system is dissipated. This brief
Introduction motivates the case for a themed issue on this topic and introduces
the topic of turbulent dissipation and heating in the solar wind. The theme issue
covers the full breadth of studies: from theory and models, massive simulations
of these models and observational studies from the highly rich and vast amount of
data collected from scores of heliospheric space missions since the dawn of the
space age. A synopsis of the theme issue is provided, where a brief description
of all the contributions is discussed and how they fit together to provide an
over-arching picture on the highly topical subject of dissipation and heating in
turbulent collisionless plasmas in general and in the solar wind in particular.
PMID- 25848078
TI - Dynamic properties of small-scale solar wind plasma fluctuations.
AB - The paper presents the latest results of the studies of small-scale fluctuations
in a turbulent flow of solar wind (SW) using measurements with extremely high
temporal resolution (up to 0.03 s) of the bright monitor of SW (BMSW) plasma
spectrometer operating on astrophysical SPECTR-R spacecraft at distances up to
350,000 km from the Earth. The spectra of SW ion flux fluctuations in the range
of scales between 0.03 and 100 s are systematically analysed. The difference of
slopes in low- and high-frequency parts of spectra and the frequency of the break
point between these two characteristic slopes was analysed for different
conditions in the SW. The statistical properties of the SW ion flux fluctuations
were thoroughly analysed on scales less than 10 s. A high level of intermittency
is demonstrated. The extended self-similarity of SW ion flux turbulent flow is
constantly observed. The approximation of non-Gaussian probability distribution
function of ion flux fluctuations by the Tsallis statistics shows the non
extensive character of SW fluctuations. Statistical characteristics of ion flux
fluctuations are compared with the predictions of a log-Poisson model. The log
Poisson parametrization of the structure function scaling has shown that well
defined filament-like plasma structures are, as a rule, observed in the turbulent
SW flows.
PMID- 25848079
TI - Third-moment descriptions of the interplanetary turbulent cascade, intermittency
and back transfer.
AB - We review some aspects of solar wind turbulence with an emphasis on the ability
of the turbulence to account for the observed heating of the solar wind.
Particular attention is paid to the use of structure functions in computing
energy cascade rates and their general agreement with the measured thermal proton
heating. We then examine the use of 1 h data samples that are comparable in
length to the correlation length for the fluctuations to obtain insights into
local inertial range dynamics and find evidence for intermittency in the computed
energy cascade rates. When the magnetic energy dominates the kinetic energy,
there is evidence of anti-correlation in the cascade of energy associated with
the outward- and inward-propagating components that we can only partially
explain.
PMID- 25848080
TI - Generation of magnetic holes in fully kinetic simulations of collisionless
turbulence.
AB - The results of three-dimensional fully kinetic simulations of decaying turbulence
with the amplitude of the fluctuating magnetic field comparable to that of the
mean field are presented. Coherent structures in the form of localized
depressions in the magnitude of the magnetic field are observed to form self
consistently in the simulations. These depressions bear considerable resemblance
to the so-called magnetic holes frequently reported in spacecraft observations.
The structures are pressure-balanced and tend to be aligned with the local
magnetic field. In the smallest structures observed, the decrease in the magnetic
field strength is compensated by an increase in the electron perpendicular
pressure, such that the transverse size of these structures is comparable to the
electron gyroradius inside the depression. It is suggested that the structures
evolve self-consistently out of the depressions in the fluctuating magnetic
field, rather than being the consequence of instability growth and saturation.
This is confirmed by additional, small-scale simulations, including those with
realistic mass ratio between protons and electrons.
PMID- 25848081
TI - Short-wavelength plasma turbulence and temperature anisotropy instabilities:
recent computational progress.
AB - Plasma turbulence consists of an ensemble of enhanced, broadband electromagnetic
fluctuations, typically driven by multi-wave interactions which transfer energy
in wavevector space via non- linear cascade processes. Temperature anisotropy
instabilities in collisionless plasmas are driven by quasi-linear wave-particle
interactions which transfer particle kinetic energy to field fluctuation energy;
the resulting enhanced fluctuations are typically narrowband in wavevector
magnitude and direction. Whatever their sources, short-wavelength fluctuations
are those at which charged particle kinetic, that is, velocity-space, properties
are important; these are generally wavelengths of the order of or shorter than
the ion inertial length or the thermal ion gyroradius. The purpose of this review
is to summarize and interpret recent computational results concerning short
wavelength plasma turbulence, short-wavelength temperature anisotropy
instabilities and relationships between the two phenomena.
PMID- 25848082
TI - Anisotropy in solar wind plasma turbulence.
AB - A review of spectral anisotropy and variance anisotropy for solar wind
fluctuations is given, with the discussion covering inertial range and
dissipation range scales. For the inertial range, theory, simulations and
observations are more or less in accord, in that fluctuation energy is found to
be primarily in modes with quasi-perpendicular wavevectors (relative to a
suitably defined mean magnetic field), and also that most of the fluctuation
energy is in the vector components transverse to the mean field. Energy transfer
in the parallel direction and the energy levels in the parallel components are
both relatively weak. In the dissipation range, observations indicate that
variance anisotropy tends to decrease towards isotropic levels as the electron
gyroradius is approached; spectral anisotropy results are mixed. Evidence for and
against wave interpretations and turbulence interpretations of these features
will be discussed. We also present new simulation results concerning evolution of
variance anisotropy for different classes of initial conditions, each with
typical background solar wind parameters.
PMID- 25848083
TI - The role of turbulence in coronal heating and solar wind expansion.
AB - Plasma in the Sun's hot corona expands into the heliosphere as a supersonic and
highly magnetized solar wind. This paper provides an overview of our current
understanding of how the corona is heated and how the solar wind is accelerated.
Recent models of magnetohydrodynamic turbulence have progressed to the point of
successfully predicting many observed properties of this complex, multi-scale
system. However, it is not clear whether the heating in open-field regions comes
mainly from the dissipation of turbulent fluctuations that are launched from the
solar surface, or whether the chaotic 'magnetic carpet' in the low corona
energizes the system via magnetic reconnection. To help pin down the physics, we
also review some key observational results from ultraviolet spectroscopy of the
collisionless outer corona.
PMID- 25848084
TI - Kinetic scale turbulence and dissipation in the solar wind: key observational
results and future outlook.
AB - Turbulence is ubiquitous in the solar wind. Turbulence causes kinetic and
magnetic energy to cascade to small scales where they are eventually dissipated,
adding heat to the plasma. The details of how this occurs are not well
understood. This article reviews the evidence for turbulent dissipation and
examines various diagnostics for identifying solar wind regions where dissipation
is occurring. We also discuss how future missions will further enhance our
understanding of the importance of turbulence to solar wind dynamics.
PMID- 25848085
TI - Intermittency, nonlinear dynamics and dissipation in the solar wind and
astrophysical plasmas.
AB - An overview is given of important properties of spatial and temporal
intermittency, including evidence of its appearance in fluids, magnetofluids and
plasmas, and its implications for understanding of heliospheric plasmas. Spatial
intermittency is generally associated with formation of sharp gradients and
coherent structures. The basic physics of structure generation is ideal, but when
dissipation is present it is usually concentrated in regions of strong gradients.
This essential feature of spatial intermittency in fluids has been shown recently
to carry over to the realm of kinetic plasma, where the dissipation function is
not known from first principles. Spatial structures produced in intermittent
plasma influence dissipation, heating, and transport and acceleration of charged
particles. Temporal intermittency can give rise to very long time correlations or
a delayed approach to steady-state conditions, and has been associated with
inverse cascade or quasi-inverse cascade systems, with possible implications for
heliospheric prediction.
PMID- 25848086
TI - A stuck haemodialysis central venous catheter: not quite open and shut!
AB - Removal of tunnelled central venous catheters can become complex if left in situ
for a prolonged period. We report a challenging case of a stuck tunnelled
haemodialysis catheter, which required sternotomy with cardio-pulmonary bypass
for retrieval. A 47-year-old female had failed attempts to remove the venous limb
of a Tessio line on the ward. A cut down on the internal jugular vein and
division of the fibrin sheath failed to release it. Synchronous traction was
applied via a snare inserted through a femoral approach. On table trans
oesophageal echocardiogram showed the tip of the catheter traversing the
tricuspid valve. At sternotomy with cardio-pulmonary bypass, the tip of the
catheter was found attached to the septal leaflet of the tricuspid valve
requiring release and repair. The management of stuck line has potential serious
complications. Prophylactic catheter exchange should be considered to avoid
complications.
PMID- 25848087
TI - Solid pseudopapillary tumor of the pancreas in a patient with cervical cancer:
relation of E-cadherin/beta-catenin adhesion complex in their carcinogenesis.
AB - Solid pseudopapillary tumor (SPT) of the pancreas is one of the most uncommon
histotypes of all exocrine pancreatic neoplasms. Disorganization of E-cadherin
and beta-catenin mutations, two key components of the Wnt signal transduction
pathway, has been implicated in the development of SPT, but not other pancreatic
tumors. Loss of E-cadherin/beta-catenin proteins and tyrosine phosphorylation of
E-cadherin/beta-catenin have been postulated in cervical carcinogenesis and
cancer invasion. A 38-year-old married woman, who had undergone brachytherapy,
radiotherapy and chemotherapy for cervical cancer in Philippines in 2011, was
admitted to our hospital after follow-up CT scan of abdomen in 2012 revealed a
lesion in the tail of pancreas. The patient underwent distal pancreatectomy and
splenectomy. The pathological diagnosis was SPT of pancreas. We suspect that the
concurrent SPT pancreas and cervical cancer in this woman were triggered by a
primary insult, a process in which E-cadherin/beta-catenin/Wnt-signaling pathway
played important roles.
PMID- 25848088
TI - Giant sialolith of submandibular gland: report of a case?.
AB - Sialolithiasis is one of the most common diseases of salivary glands in middle
aged patients. Sialoliths are localized in submandibular glands in nearly 80% of
the reported cases and they are classified as 'giant' in case any dimension
exceeds 15 mm. Giant sialolith in submandibular gland is a rare disorder. Here,
an unusual case of giant sialolith in submandibular gland is reported. A 42-year
old man referred with complaints of recurrent pain and swelling in the left
submandibular area. Computerized tomography revealed a calcified mass of 42 * 17
mm size within the submandibular gland. Excision was performed in the
submandibular gland and a giant sialolith of 35 mm length localized in the body
of the gland was detected. The postoperative period was uneventful and the
patient fully recovered.
PMID- 25848089
TI - Quality Control Pathways for Nucleus-Encoded Eukaryotic tRNA Biosynthesis and
Subcellular Trafficking.
AB - tRNAs perform an essential role in translating the genetic code. They are long
lived RNAs that are generated via numerous posttranscriptional steps. Eukaryotic
cells have evolved numerous layers of quality control mechanisms to ensure that
the tRNAs are appropriately structured, processed, and modified. We describe the
known tRNA quality control processes that check tRNAs and correct or destroy
aberrant tRNAs. These mechanisms employ two types of exonucleases, CCA end
addition, tRNA nuclear aminoacylation, and tRNA subcellular traffic. We arrange
these processes in order of the steps that occur from generation of precursor
tRNAs by RNA polymerase (Pol) III transcription to end maturation and
modification in the nucleus to splicing and additional modifications in the
cytoplasm. Finally, we discuss the tRNA retrograde pathway, which allows tRNA
reimport into the nucleus for degradation or repair.
PMID- 25848090
TI - Histone methyltransferase Setd8 represses Gata2 expression and regulates
erythroid maturation.
AB - Setd8 is the sole histone methyltransferase in mammals capable of monomethylating
histone H4 lysine 20 (H4K20me1). Setd8 is expressed at significantly higher
levels in erythroid cells than any other cell or tissue type, suggesting that
Setd8 has an erythroid-cell-specific function. To test this hypothesis, stable
Setd8 knockdown was established in extensively self-renewing erythroblasts
(ESREs), a well-characterized, nontransformed model of erythroid maturation.
Knockdown of Setd8 resulted in impaired erythroid maturation characterized by a
delay in hemoglobin accumulation, larger mean cell area, persistent ckit
expression, incomplete nuclear condensation, and lower rates of enucleation.
Setd8 knockdown did not alter ESRE proliferation or viability or result in
accumulation of DNA damage. Global gene expression analyses following Setd8
knockdown demonstrated that in erythroid cells, Setd8 functions primarily as a
repressor. Most notably, Gata2 expression was significantly higher in knockdown
cells than in control cells and Gata2 knockdown rescued some of the maturation
impairments associated with Setd8 disruption. Setd8 occupies critical regulatory
elements in the Gata2 locus, and knockdown of Setd8 resulted in loss of H4K20me1
and gain of H4 acetylation at the Gata2 1S promoter. These results suggest that
Setd8 is an important regulator of erythroid maturation that works in part
through repression of Gata2 expression.
PMID- 25848091
TI - Role for Protein Kinase A in the Neurospora Circadian Clock by Regulating White
Collar-Independent frequency Transcription through Phosphorylation of RCM-1.
AB - Rhythmic activation and repression of clock gene expression is essential for the
eukaryotic circadian clock functions. In the Neurospora circadian oscillator, the
transcription of the frequency (frq) gene is periodically activated by the White
Collar (WC) complex and suppressed by the FRQ-FRH complex. We previously showed
that there is WC-independent frq transcription and its repression is required for
circadian gene expression. How WC-independent frq transcription is regulated is
not known. We show here that elevated protein kinase A (PKA) activity results in
WC-independent frq transcription and the loss of clock function. We identified
RCM-1 as the protein partner of RCO-1 and an essential component of the clock
through its role in suppressing WC-independent frq transcription. RCM-1 is a
phosphoprotein and is a substrate of PKA in vivo and in vitro. Mutation of the
PKA-dependent phosphorylation sites on RCM-1 results in WC-independent
transcription of frq and impaired clock function. Furthermore, we showed that RCM
1 is associated with the chromatin at the frq locus, a process that is inhibited
by PKA. Together, our results demonstrate that PKA regulates frq transcription by
inhibiting RCM-1 activity through RCM-1 phosphorylation.
PMID- 25848094
TI - Estimation of organ doses and effective doses in image-guided respiration-gated
radiotherapy.
AB - Dose conformity in thoracic and abdominal ion-beam radiotherapy is degraded by
respiratory motion. To improve conformity, an image-guided respiration-gated
system can be used in the treatment room. The purpose of this study was to
estimate the organ doses and effective doses to patients from an image-guided
respiration-gated system. Glass dosemeters were inserted into an adult
anthropomorphic phantom and were attached to the surface on the phantom. The
phantom was placed on the treatment couch, and the imaging dose from fluoroscopy
was evaluated. In addition to the organ doses, the effective doses were also
estimated according to the ICRP Publication 103. The irradiation time is over 3-5
min per beam angle. When image acquisition conditions were assumed for thoracic
treatment, the effective doses and maximal skin doses were 0.48-0.79 mSv and 5.9
9.9 mGy, respectively. The estimated doses can be the base data for considering
radiological protection in the radiotherapy.
PMID- 25848093
TI - Structural Basis for Pharmacology of Voltage-Gated Sodium and Calcium Channels.
AB - Voltage-gated sodium channels initiate action potentials in nerve, muscle, and
other electrically excitable cells. Voltage-gated calcium channels are activated
by depolarization during action potentials, and calcium influx through them is
the key second messenger of electrical signaling, initiating secretion,
contraction, neurotransmission, gene transcription, and many other intracellular
processes. Drugs that block sodium channels are used in local anesthesia and the
treatment of epilepsy, bipolar disorder, chronic pain, and cardiac arrhythmia.
Drugs that block calcium channels are used in the treatment of epilepsy, chronic
pain, and cardiovascular disorders, including hypertension, angina pectoris, and
cardiac arrhythmia. The principal pore-forming subunits of voltage-gated sodium
and calcium channels are structurally related and likely to have evolved from
ancestral voltage-gated sodium channels that are widely expressed in prokaryotes.
Determination of the structure of a bacterial ancestor of voltage-gated sodium
and calcium channels at high resolution now provides a three-dimensional view of
the binding sites for drugs acting on sodium and calcium channels. In this
minireview, we outline the different classes of sodium and calcium channel drugs,
review studies that have identified amino acid residues that are required for
their binding and therapeutic actions, and illustrate how the analogs of those
key amino acid residues may form drug-binding sites in three-dimensional models
derived from bacterial channels.
PMID- 25848095
TI - Paediatric doses in St Petersburg hospitals.
AB - The exposure of paediatric patients during X-ray examinations in St Petersburg
hospitals was investigated. Data about radiography examinations were collected,
and mean patient effective doses and entrance surface air kerma for each X-ray
unit were estimated. The results of the study were compared with other countries
practice. This data will be used to optimise paediatric conventional X-ray
examinations in Russia.
PMID- 25848096
TI - Reduction of occupational radiation dose in staff at the cardiac catheterisation
laboratory by protective material placed on the patient.
AB - Reducing occupational radiation dose in cardiac catheterisation laboratories is
one of the objectives of the radiation protection system because the procedures
performed involve high levels of radiation compared with others in health care.
Recommendations on protection methods used are referred to different structural
types and personal protection tools. In this work, the effectiveness of a
shielding drape above the patient in different geometric shapes for a standard
procedure in interventional cardiology was evaluated. Values of personal dose
equivalent Hp(10) obtained simultaneously with three active electronic
semiconductor dosemeters located at the usual position of staff and at the C-arm
have been used to show the usefulness of the shielding drape.
PMID- 25848097
TI - Reaction mechanism interplay in determining the biological effectiveness of
neutrons as a function of energy.
AB - Neutron relative biological effectiveness (RBE) is found to be energy dependent,
being maximal for energies ~1 MeV. This is reflected in the choice of radiation
weighting factors wR for radiation protection purposes. In order to trace back
the physical origin of this behaviour, a detailed study of energy deposition
processes with their full dependences is necessary. In this work, the Monte Carlo
transport code PHITS was used to characterise main secondary products responsible
for energy deposition in a 'human-sized' soft tissue spherical phantom,
irradiated by monoenergetic neutrons with energies around the maximal RBE/wR.
Thereafter, results on the microdosimetric characterisation of secondary protons
were used as an input to track structure calculations performed with PARTRAC,
thus evaluating the corresponding DNA damage induction. Within the proposed
simplified approach, evidence is suggested for a relevant role of secondary
protons in inducing the maximal biological effectiveness for 1 MeV neutrons.
PMID- 25848098
TI - Nanodosimetric descriptors of the radiation quality of carbon ions.
AB - In view of the emerging interest of carbon ions in radiotherapy and of the strong
correlation between the track structure and the radiobiological effectiveness of
ionising radiations, the track-structure properties of (12)C-ions were studied at
particle energies close to the Bragg peak. To perform the investigations,
ionisation-cluster-size distributions for nanometre-sized target volumes were
measured with the track-nanodosimeter installed at the TANDEM-ALPI accelerator
complex at LNL, and calculated using a dedicated Monte Carlo simulation code. The
resulting cluster-size distributions are used to derive particular descriptors of
particle track structure. Here, the main emphasis is laid on the mean ionisation
cluster size M1 and the cumulative probability Fk of measuring cluster sizes nu
>= k. From the radiobiological point of view, Fk is of particular interest
because an increasing k corresponds to an increase of damages of higher
complexity. In addition, Fk saturates with increasing radiation quality like
radiobiological cross sections as a function of linear energy transfer. Results
will be presented and discussed for (12)C-ions at 96 and 240 MeV.
PMID- 25848099
TI - Radiation protection aspects of EMITEL Encyclopaedia of Medical Physics.
AB - The Encyclopaedia of Medical Physics EMITEL was developed under the EU pilot
project European Medical Imaging Technology e-Encyclopaedia for Lifelong
Learning. This large reference material includes 3400 articles on 2100 pages
supported by thousands of illustrations. All materials are available free at the
website, www.emitel2.eu. The articles are grouped in seven categories--physics
of: X-ray diagnostic radiology, nuclear medicine, radiotherapy, magnetic
resonance imaging, ultrasound imaging, radiation protection and general terms.
The radiation protection part of EMITEL includes 450 articles. These were
organised in several sub-groups including: nuclear and atomic physics; ionizing
radiation interactions and biological effects; radiation detection and
measurement; dosimetric quantities and units; and general radiation protection
and international bodies. EMITEL project was developed over 3 y and attracted as
contributors 250+ senior specialists from 35 countries. After its successful
launching, EMITEL is actively used by thousands of professionals around the
world.
PMID- 25848100
TI - Collective effective dose from diagnostic radiology in Ukraine.
AB - The frequencies and effective doses for the most common X-ray diagnostic
examinations in Ukraine were assessed in the frame of the European Commission
(EC) Study on European Population Doses from Medical Exposure (Dose Datamed 2).
The average effective doses for all radiographic procedures were estimated using
the ODS-60 software (Finland). The estimation of the effective doses for the
chest film fluorography was carried out from the results of own representative
measurements with thermoluminescent (TL) dosimetry and a standard Alderson-Rando
phantom. The effective doses for fluoroscopy procedures were assessed using the
Russian guidelines for estimation of effective doses. For all other X-ray
examinations and procedures [computed tomography (CT), angiography and
interventional procedures], typical effective dose values were taken from the EC
Guidance RP154. The most frequently performed in Ukraine is chest film
fluorography, with 389 examinations per 1000 population annually, reflecting in
the greatest contribution to the total collective effective dose (CED) of 428 mSv
per 1000 population (44 %). The total frequency and CED from all X-ray diagnostic
examinations and procedures were estimated to be 1218 examinations and 1060 mSv
per 1000 populations, respectively. The expected additional cancer risk from X
ray diagnostic examinations and interventional procedures is 2680 cases per year,
with 1200 of them due to the contribution of chest fluorography. The main
important action in radiation protection of patients in diagnostic radiology is
the organisation of the monitoring of patient doses for different types of X-ray
diagnostic examinations and replacement of chest film fluorography with digital X
ray systems.
PMID- 25848101
TI - Mechanisms of the induction of apoptosis mediated by radiation-induced cytokine
release.
AB - The aim of the present work was to investigate the mechanisms of radiation
induced bystander signalling leading to apoptosis in non-irradiated co-cultured
cells. Cultured non-transformed cells were irradiated, and the effect on the
apoptosis rate on co-cultured non-irradiated malignant cells was determined. For
this, two different levels of the investigation are presented, i.e. release of
signalling proteins and transcriptomic profiling of the irradiated and non
irradiated co-cultured cells. Concerning the signalling proteins, in this study,
the attention was focussed on the release of the active and latent forms of the
transforming growth factor-beta1 protein. Moreover, global gene expression
profiles of non-transformed and transformed cells in untreated co-cultures were
compared with those of 0.5-Gy-irradiated non-transformed cells co-cultured with
the transformed cells. The results show an effect of radiation on the release of
signalling proteins in the medium, although no significant differences in release
rates were detectable when varying the doses in the range from 0.25 to 1 Gy.
Moreover, gene expression results suggest an effect of radiation on both cell
populations, pointing out specific signalling pathways that might be involved in
the enhanced induction of apoptosis.
PMID- 25848102
TI - Romanian medical exposure to ionising radiation in 2012.
AB - Medical exposure, the main source of artificial exposure, shows an increasing
trend in the last years, manifested both by increasing the number of examinations
with ionising radiation and by increasing the patient dose level. Annual results
obtained for medical exposure to ionising radiation based on the data collected
from Romanian hospitals are useful for the update of the national database and
optimisation of diagnostic procedures in radiology and nuclear medicine. Medical
exposure level is expressed in terms of annual collective dose and is evaluated
from annual frequencies and the average effective dose per procedure for
different types of radiological and nuclear medicine procedures. The Romanian
hospitals reported during 2012 a number of 5,505,792 radiological examinations
and 17,088 diagnostic procedures of nuclear medicine. Based on the data reported,
the average effective doses and their contributions to the collective dose were
evaluated. The main contributions to the collective dose of the radiological
procedures are registered for CT abdomen and pelvis region, followed by thorax CT
and head CT examinations. The next positions are fluoroscopic examination of the
thorax and gastrointestinal disease and radiographic examination of the lumbar
spine and thorax, which in spite of their low effective dose have an important
contribution to the collective dose due to the large number of examinations. For
nuclear medicine procedures, major contributions to collective dose are given by
bone scintigraphy, followed by PET-CT and thyroid scintigraphy.
PMID- 25848103
TI - Evaluation of organ doses in adult and paediatric CT examinations based on Monte
Carlo simulations and in-phantom dosimetry.
AB - The aim of this study was to validate the computed tomography dose index (CTDI)
and organ doses evaluated by Monte Carlo simulations through comparisons with
doses evaluated by in-phantom dosimetry. Organ doses were measured with radio
photoluminescence glass dosemeter (RGD) set at various organ positions within
adult and 1-y-old anthropomorphic phantoms. For the dose simulations, the X-ray
spectrum and bow-tie filter shape of a CT scanner were estimated and 3D voxelised
data of the CTDI and anthropomorphic phantoms from the acquired CT images were
derived. Organ dose simulations and measurements were performed with chest and
abdomen-pelvis CT examination scan parameters. Relative differences between the
simulated and measured doses were within 5 % for the volume CTDI and 13 % for
organ doses for organs within the scan range in adult and paediatric CT
examinations. The simulation results were considered to be in good agreement with
the measured doses.
PMID- 25848104
TI - Staff eye doses in a large medical centre in Saudi Arabia: are they meeting the
new ICRP recommendations?
AB - A 5-y retrospective analysis of the cardiology staff eye doses was performed on
34 staff from different categories (cardiologists, nurses and technologists) at
King Faisal Specialist Hospital and Research Centre (KFSHRC) in Riyadh, Saudi
Arabia. KFSHRC is a tertiary medical centre with 800-bed capacity having more
than 5000 cardiac catheterisation procedures performed annually. The aim of the
study is to derive staff doses to the lens of the eyes using the personal dose
equivalent Hp(0.07) values from the annual TLD dose report for the years 2008
2012 and determine the category of staff with high estimated eye doses. The study
also aims to investigate the causes for high doses and recommend dose-reduction
techniques. The dose to the lens of the eye was estimated by using the ratio
Hp(0.07)slab/Hlens of 1.1 where Hp(0.07) values are the reported doses read from
TLD badge worn at the collar level. The average annual eye dose of each category
for the 5-y monitoring period was determined. Cardiologists tend to receive
higher doses than the nurses by a factor of 2-4 and can exceed 5 mSv y(-1). No
correlation exists between the eye doses of nurses and the cardiologists. There
is a need to use a conversion coefficient in terms of eye lens dose per dose-area
product for faster estimation of eye lens doses. However, there is a limitation
on the use of the conversion coefficient because it will depend on the clinical
procedure and the X-ray tube angulation. Further investigation on this limitation
is needed.
PMID- 25848105
TI - Patient doses from PET-CT procedures.
AB - Positron emission tomography (PET) was installed for the first time in Bulgaria
in 2009, and nowadays two hybrid PET-computed tomography (CT) systems are in
operation. The aim of this work is to estimate patient doses from PET-CT
procedures and to explore potential for optimisation. Data were retrospectively
collected for 50 patients examined with the system Philips Gemini TF and for 58
patients examined with the system GE Discovery 600. Whole-body examinations with
radiopharmaceutical (18)F-2-fluoro-2-deoxy-D-glucose (FDG) were performed on all
patients. Patient effective doses from the CT component of the examination were
calculated with CT Expo software and compared with doses estimated applying the
National Radiological Protection Board (NRPB) conversion coefficients. Effective
doses from the PET component were calculated applying the ICRP 80 conversion
coefficients. For the first system, average effective doses from CT component
were 8.0 and 8.9 mSv, applying CT Expo and NRPB coefficients, respectively, and
4.9 mSv from PET component. For the second system, the corresponding values were
7.8, 8.7 and 5.9 mSv. These results for patient effective doses are relatively
lower or comparable to other similar surveys. Reasons for the observed
differences are analysed and presented.
PMID- 25848106
TI - Cutting down the radiation dose on CT urography: how it is done and what results
are received?
AB - Computed tomography urography (CTU) is a very detailed and powerful method of
investigating the urinary tract, but an individual approach to each patient is
recommended considering also the radiation dose. This article aims to present the
initial experience from the diagnosis of urinary tract diseases and congenital
variants in the anatomy of the urinary system using low-kV protocols. The image
quality and patient dose in CTU were compared when replacing the standard 120-kV
protocol with two different low-kV protocols. Totally, 91 patients (41 women and
55 men) with mean age 56.4 were studied with three different low-dose protocols.
The patients underwent an unenhanced and excretory low-dose phases and standard
corticomedullary and nephrographic phases. Effective dose was reduced by more
than 65 % using the 100-kV protocol and by more than 76 % with introduction of 80
kV protocol. At the same time, patient images obtained with the new low-kV
protocols maintained their diagnostic quality.
PMID- 25848107
TI - Digital breast tomosynthesis in one or two views as a replacement or adjunct
technique to full-field digital mammography.
AB - Clinical studies using different imaging protocols to perform digital breast
tomosynthesis (DBT) were reviewed (2008-14) to assess interpretive accuracy.
Descriptive pooled statistics were used to estimate and summarise accuracy
measures for each type of imaging protocol in relation to that of two-view full
field digital mammography (FFDM). In studies comparing multiple DBT imaging
protocols, a trend of increased performance was often seen when including both
the mediolateral oblique and craniocaudal views for DBT alone and even more so
for DBT adjunct to FFDM. Overall, the average DeltaAUC (%; sd) across studies for
stand-alone DBT (relative to FFDM), in one and in two views, were 2.2 (+/- 3.7)
and 5.9 (+/- 4.6), and when used together with FFDM, 3.9 (+/- 2.0) and 6.7 (+/-
0.9). With respect to individual studies, improvements in accuracy using DBT were
present for different types of imaging protocols although the magnitude of the
impact varied between studies, and some studies did not show significant
improvements in comparison with FFDM. The most consistent effect of improvement
in breast cancer detection was seen across studies for two-view DBT with FFDM.
These summary findings may depend on the sampling constraints present in
tomosynthesis imaging and on other factors discussed in this paper. In order to
investigate these effects more thoroughly and how they might impact outcomes,
comparative or randomized-controlled trials are warranted.
PMID- 25848108
TI - Nanodosimetric track structure in homogeneous extended beams.
AB - Physical aspects of particle track structure are important in determining the
induction of clustered damage in relevant subcellular structures like the DNA and
higher-order genomic structures. The direct measurement of track-structure
properties of ionising radiation is feasible today by counting the number of
ionisations produced inside a small gas volume. In particular, the so-called
track-nanodosimeter, installed at the TANDEM-ALPI accelerator complex of LNL,
measures ionisation cluster-size distributions in a simulated subcellular
structure of dimensions 20 nm, corresponding approximately to the diameter of the
chromatin fibre. The target volume is irradiated by pencil beams of primary
particles passing at specified impact parameter. To directly relate these
measured track-structure data to radiobiological measurements performed in broad
homogeneous particle beams, these data can be integrated over the impact
parameter. This procedure was successfully applied to 240 MeV carbon ions and
compared with Monte Carlo simulations for extended fields.
PMID- 25848109
TI - Role of cardiac ultrafast cameras with CZT solid-state detectors and software
developments on radiation absorbed dose reduction to the patients.
AB - Myocardial perfusion imaging (MPI) is one the most contributing nuclear medicine
technique to the annual population dose. The purpose of this study is to compare
radiation-absorbed doses to the patients examined by conventional cardiac SPECT
(CSPECT) camera and ultrafast cardiac (UFC) camera with cadmium-zinc-telluride
(CZT) solid-state detectors. Total injected activity was reduced by 50 % when
both stress and rest images were acquired and by 75 % when only stress images
were taken with UFC camera. As a result of this, the mean total effective dose
was found significantly lower with UFC camera (2.2 +/- 1.2 mSv) than CSPECT (7.7
+/- 3.8 mSv) (p < 0.001). Further dose reduction was obtained by reducing
equivocal test results and unnecessary additional examinations with UFC camera.
Using UFC camera, MPI can be conveniently used for the detection of coronary
artery disease (CAD) much less increasing annual population radiation dose as it
had been before.
PMID- 25848110
TI - Looking into future: challenges in radiation protection in medicine.
AB - Radiation protection in medicine is becoming more and more important with
increasing wider use of X-rays, documentation of effects besides the potential
for long-term carcinogenic effects. With computed tomography (CT) likely to
become sub-mSv in coming years, positron emission tomography (PET), single photon
emission computed tomography (SPECT) and some of the nuclear medical examination
will become focus of attraction as high-dose examinations, even though they are
less-frequent ones. Clarity will be needed on radiation effects at levels of
radiation doses encountered in a couple of CT scans and if effects are really
cumulative. There is challenge to develop radiation metrics that can be used as
easily as units of temperature and length and avoidance of multiple meaning of a
single dose metric. Other challenges include development of biological indicators
of radiation dose, transition from dose to a representative phantom to dose to
individual patient, system for tracking of radiation exposure history of patient,
avoidance of radiation-induced skin injury in patients and radiation cataract in
staff, cutting down inappropriate referrals for radiological examinations,
confidence building in patient and patient safety in radiotherapy.
PMID- 25848111
TI - Patient radiation doses during coronary interventions in four Croatian hospitals:
4-y comparison.
AB - The number of coronary interventions increased substantially in the recent years.
Although of great benefit to patients, these procedures can subject patients to
considerable radiation doses. There is a legal framework for patient dose
measurements in Croatia during radiological procedures, but in practice, it
applies only occasionally. A quality control manual, established at the
University Hospital Osijek, was accepted by other major cardiology centres in
Croatia; besides checking the technical characteristics of the device, it
provides constant measurement and analysis of patient doses in interventional
cardiology. It also includes patient examination for radiation skin injuries in
case of dose of >2 Gy. The aim of the study was to determine and compare patient
radiation doses during cardiological interventions measured within 4 y in four
major cardiology centres with the values proposed by the European Commission and
other professional bodies. The local reference dose levels were also set.
PMID- 25848112
TI - An evaluation of the shielding effectiveness of lead aprons used in clinics for
protection against ionising radiation from novel radioisotopes.
AB - The purpose of this study is to evaluate the effectiveness of personal radiation
shields currently worn in hospital and other diagnostic environments. This study
was performed with four different radioisotopes; (18)F, (99m)Tc, (124)I and
(131)I. (18)F results showed a decrease in dose with 0.5-mm Pb shielding but the
reduction provided does not warrant its use clinically. (124)I testing
demonstrated that dose enhancement can occur in greater shield thicknesses. PET
isotope (124)I can be adequately shielded using 0.25-mm Pb equivalent aprons but
any higher thickness increase the wearer's dose. As a result more shielding does
not always equal more protection. The (131)I test showed that no dose reduction
occurred, even when tested with up to 1.25-mm Pb equivalent shielding. Novel
radioisotopes being used in the laboratory and clinic should be individually
tested as each requires specific shielding testing.
PMID- 25848113
TI - Assessment of the occupational exposure in real time during interventional
cardiology procedures.
AB - Interventional cardiology (IC) procedures can be complex, requiring the operators
to work near the patient, during long exposure times. Owing to scattered
radiation in the patient and the fluoroscopic equipment, the medical staff are
exposed to a non-uniform radiation field and can receive high radiation doses. In
this study, it is proposed to analyse staff doses obtained in real time, during
IC procedures. A system for occupational dosimetry in real time was used. In
order to identify some parameters that may affect the staff doses, Monte Carlo
(MC) calculations, using MCNPX v.2.7.0 code and voxel phantoms, were performed.
The data obtained from measurements, together with MC simulations, allowed the
identification of actions and behaviours of the medical staff that could be
considered a risk under routine working conditions. The implementation of this
monitoring system for exposure of personnel may have a positive effect on
optimisation of radiological protection in fluoroscopically guided cardiac
procedures.
PMID- 25848114
TI - How to use the equipment you have for appropriate quality at low radiation dose.
AB - A CT department's ability to image with low radiation doses is determined
primarily by the CT scan protocols and the radiologists' image quality
expectations and to a lesser extent by the dose-reduction features available. The
CT technology level has a smaller influence than might be expected. There are,
however, exceptions where dose is directly linked to the scanner's technical
capabilities. The key to appropriate image quality with low radiation dose is
therefore optimised scan protocols. To optimise effectively, an in-depth
understanding of the technical performance of the scanner is required. Therefore,
optimisation is best carried out by a multi-disciplinary team that includes
radiologists, technologists and medical physics experts. This article describes
practical strategies for carrying out such exercises.
PMID- 25848115
TI - Collective effective dose in Europe from X-ray and nuclear medicine procedures.
AB - Population doses from radiodiagnostic (X-ray and nuclear medicine) procedures in
Europe were estimated based on data collected from 36 European countries. For X
ray procedures in EU and EFTA countries (except Liechtenstein) the collective
effective dose is 547,500 man Sv, resulting in a mean effective dose of 1.06 mSv
per caput. For all European countries included in the survey the collective
effective dose is 605,000 man Sv, resulting in a mean effective dose of 1.05 mSv
per caput. For nuclear medicine procedures in EU countries and EFTA (except
Liechtenstein) countries the collective effective dose is 30,700 man Sv,
resulting in a mean effective dose of 0.06 mSv per caput. For all European
countries included in the survey the collective effective dose is 31,100 man Sv,
resulting in a mean effective dose of 0.05 mSv per caput.
PMID- 25848116
TI - Paediatric CT protocol optimisation: a design of experiments to support the
modelling and optimisation process.
AB - In the last decade, several studies have emphasised the need to understand and
optimise the computed tomography (CT) procedures in order to reduce the radiation
dose applied to paediatric patients. To evaluate the influence of the technical
parameters on the radiation dose and the image quality, a statistical model has
been developed using the design of experiments (DOE) method that has been
successfully used in various fields (industry, biology and finance) applied to CT
procedures for the abdomen of paediatric patients. A Box-Behnken DOE was used in
this study. Three mathematical models (contrast-to-noise ratio, noise and CTDI
vol) depending on three factors (tube current, tube voltage and level of
iterative reconstruction) were developed and validated. They will serve as a
basis for the development of a CT protocol optimisation model.
PMID- 25848117
TI - Estimation of staff lens doses during interventional procedures. Comparing
cardiology, neuroradiology and interventional radiology.
AB - The purpose of this article is to estimate lens doses using over apron active
personal dosemeters in interventional catheterisation laboratories (cardiology
IC, neuroradiology IN and radiology IR) and to investigate correlations between
occupational lens doses and patient doses. Active electronic personal dosemeters
placed over the lead apron were used on a sample of 204 IC procedures, 274 IN and
220 IR (all performed at the same university hospital). Patient dose values
(kerma area product) were also recorded to evaluate correlations with
occupational doses. Operators used the ceiling-suspended screen in most cases.
The median and third quartile values of equivalent dose Hp(10) per procedure
measured over the apron for IC, IN and IR resulted, respectively, in 21/67, 19/44
and 24/54 uSv. Patient dose values (median/third quartile) were 75/128, 83/176
and 61/159 Gy cm(2), respectively. The median ratios for dosemeters worn over the
apron by operators (protected by the ceiling-suspended screen) and patient doses
were 0.36; 0.21 and 0.46 uSv Gy(-1) cm(-2), respectively. With the conservative
approach used (lens doses estimated from the over apron chest dosemeter) we came
to the conclusion that more than 800 procedures y(-1) and per operator were
necessary to reach the new lens dose limit for the three interventional
specialties.
PMID- 25848118
TI - Eye dosimetry and protective eyewear for interventional clinicians.
AB - Doses to the eyes of interventional clinicians can exceed 20 mSv. Various
protective devices can afford protection to the eyes with the final barrier being
protective eyewear. The protection provided by lead glasses is difficult to
quantify, and the majority of dosimeters are not designed to be worn under lead
glasses. This study has measured dose reduction factors (DRFs) equal to the ratio
of the dose with no protection, divided by that when lead glasses are worn.
Glasses have been tested in X-ray fields using anthropomorphic phantoms to
simulate the patient and clinician. DRFs for X-rays incident from the front vary
from 5.2 to 7.6, while values for orientations reminiscent of clinical practice
are between 1.4 and 5.2. Results suggest that a DRF of two is a conservative
factor that could be applied to personal dosimeter measurements to account for
the dose reduction provided by most types of lead glasses.
PMID- 25848119
TI - Dosimetry audit of radiotherapy treatment planning systems.
AB - In radiotherapy Treatment Planning Systems (TPS) various calculation algorithms
are used. The accuracy of dose calculations has to be verified. Numerous phantom
types, detectors and measurement methodologies are proposed to verify the TPS
calculations with dosimetric measurements. A heterogeneous slab phantom has been
designed within a Coordinated Research Project (CRP) of the IAEA. The
heterogeneous phantom was developed in the frame of the IAEA CRP. The phantom
consists of frame slabs made with polystyrene and exchangeable inhomogeneity
slabs equivalent to bone or lung tissue. Special inserts allow to position
thermoluminescent dosimeters (TLD) capsules within the polystyrene slabs below
the bone or lung equivalent slabs and also within the lung equivalent material.
Additionally, there are inserts that allow to position films or ionisation
chamber in the phantom. Ten Polish radiotherapy centres (of 30 in total) were
audited during on-site visits. Six different TPSs and five calculation algorithms
were examined in the presence of inhomogeneities. Generally, most of the results
from TLD were within 5 % tolerance. Differences between doses calculated by TPSs
and measured with TLD did not exceed 4 % for bone and polystyrene equivalent
materials. Under the lung equivalent material, on the beam axis the differences
were lower than 5 %, whereas inside the lung equivalent material, off the beam
axis, in some cases they were of around 7 %. The TLD results were confirmed with
the ionisation chamber measurements. The comparison results of the calculations
and the measurements allow to detect limitations of TPS calculation algorithms.
The audits performed with the use of heterogeneous phantom and TLD seem to be an
effective tool for detecting the limitations in the TPS performance or beam
configuration errors at audited radiotherapy departments.
PMID- 25848120
TI - Schizophrenia, Subjectivity, and Mindreading.
AB - A number of recent articles, many appearing in Schizophrenia Bulletin, signal a
renewed interest in phenomenological approaches to our understanding of
schizophrenia. These approaches conceptualize schizophrenia as a disorder of
altered self-awareness and decreased prereflective social attunement, which may
manifest as an impaired understanding of self, others, and the physical world.
Phenomenological approaches to psychopathology are sometimes construed as being
incompatible with the reductionistic methodology of contemporary neuroscience. In
this article, we re-examine findings from the phenomenological investigation of
schizophrenia in light of an influential neurocomputational account of
mindreading, which postulates that understanding of others is subserved by
coherent internal self-models. We argue that the phenomenological approach to
schizophrenia is not incompatible with a neurocomputational account of
mindreading, and that the 2 approaches should instead be viewed as existing in a
relationship of mutual constraint and enlightenment. Our hypothesis, while
speculative, is an attempt to marry the phenomenological and neuronal realities
of schizophrenia. Furthermore, it has implications for psychotherapeutic
interventions and future research.
PMID- 25848121
TI - Tracking fusion of human mesenchymal stem cells after transplantation to the
heart.
AB - Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid
recovery of damaged myocardium caused by myocardial infarction. One possible
mechanism for MSC-mediated recovery is reprogramming after cell fusion between
transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based
luciferase reporter system coupled to biophotonic imaging to detect fusion of
transplanted human pluripotent stem cell-derived MSCs to cells of organs of
living mice. Human MSCs, with transient expression of a viral fusogen, were
delivered to the murine heart via a collagen patch. At 2 days and 1 week later,
living mice were probed for bioluminescence indicative of cell fusion. Cell
fusion was detected at the site of delivery (heart) and in distal tissues (i.e.,
stomach, small intestine, liver). Fusion was confirmed at the cellular scale via
fluorescence in situ hybridization for human-specific and mouse-specific
centromeres. Human cells in organs distal to the heart were typically located
near the vasculature, suggesting MSCs and perhaps MSC fusion products have the
ability to migrate via the circulatory system to distal organs and engraft with
local cells. The present study reveals previously unknown migratory patterns of
delivered human MSCs and associated fusion products in the healthy murine heart.
The study also sets the stage for follow-on studies to determine the functional
effects of cell fusion in a model of myocardial damage or disease. SIGNIFICANCE:
Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other
tissues to recover lost function or at least limit overactive immune responses.
Analysis of tissues after MSC transplantation shows evidence of fusion between
MSCs and the cells of the recipient. To date, the biologic implications of cell
fusion remain unclear. A newly developed in vivo tracking system was used to
identify MSC fusion products in living mice. The migratory patterns of fusion
products were determined both in the target organ (i.e., the heart) and in distal
organs. This study shows, for the first time, evidence of fusion products at
sites distal from the target organ and data to suggest that migration occurs via
the vasculature. These results will inform and improve future, MSC-based
therapeutics.
PMID- 25848122
TI - Bioengineering a human plasma-based epidermal substitute with efficient grafting
capacity and high content in clonogenic cells.
AB - Cultured epithelial autografts (CEAs) produced from a small, healthy skin biopsy
represent a lifesaving surgical technique in cases of full-thickness skin burn
covering >50% of total body surface area. CEAs also present numerous drawbacks,
among them the use of animal proteins and cells, the high fragility of
keratinocyte sheets, and the immaturity of the dermal-epidermal junction, leading
to heavy cosmetic and functional sequelae. To overcome these weaknesses, we
developed a human plasma-based epidermal substitute (hPBES) for epidermal
coverage in cases of massive burn, as an alternative to traditional CEA, and set
up critical quality controls for preclinical and clinical studies. In this study,
phenotypical analyses in conjunction with functional assays (clonal analysis,
long-term culture, or in vivo graft) showed that our new substitute fulfills the
biological requirements for epidermal regeneration. hPBES keratinocytes showed
high potential for cell proliferation and subsequent differentiation similar to
healthy skin compared with a well-known reference material, as ascertained by a
combination of quality controls. This work highlights the importance of
integrating relevant multiparameter quality controls into the bioengineering of
new skin substitutes before they reach clinical development. SIGNIFICANCE: This
work involves the development of a new bioengineered epidermal substitute with
pertinent functional quality controls. The novelty of this work is based on this
quality approach.
PMID- 25848124
TI - A Prorating Method for Estimating MMPI-2-RF Scores From MMPI Responses:
Examination of Score Fidelity and Illustration of Empirical Utility in the
PERSEREC Police Integrity Study Sample.
AB - The purpose of the current study was to identify Minnesota Multiphasic
Personality Inventory-2-Restructured Form (MMPI-2-RF) correlates of police
officer integrity violations and other problem behaviors in an archival database
with original MMPI item responses and collateral information regarding integrity
violations obtained for 417 male officers. In Study 1, we estimated MMPI-2-RF
scores from the MMPI item pool (which includes approximately 80% of the MMPI-2-RF
items) in a normative sample, a psychiatric inpatient sample, and a police
officer sample, and conducted analyses that demonstrated the comparability of
estimated and full scale scores for 41 of the 51 MMPI-2-RF scales. In Study 2, we
correlated estimated MMPI-2-RF scores with information about subsequent integrity
violations and problem behaviors from the integrity violation data set. Several
meaningful associations were obtained, predominately with scales from the
emotional, thought, and behavioral dysfunction domains of the MMPI-2-RF.
Application of a correction for range restriction yielded substantially improved
validity estimates. Finally, we calculated relative risk ratios for the
statistically significant findings using cutoffs lower than 65T, which is
traditionally used to identify clinically significant elevations, and found
several meaningful relative risk ratios.
PMID- 25848125
TI - Erratum.
PMID- 25848123
TI - Concise Review: Macrophages: Versatile Gatekeepers During Pancreatic beta-Cell
Development, Injury, and Regeneration.
AB - Macrophages are classically considered detrimental for pancreatic beta-cell
survival and function, thereby contributing to beta-cell failure in both type 1
(T1D) and 2 (T2D) diabetes mellitus. In addition, adipose tissue macrophages
negatively influence peripheral insulin signaling and promote obesity-induced
insulin resistance in T2D. In contrast, recent data unexpectedly uncovered that
macrophages are not only able to protect beta cells during pancreatitis but also
to orchestrate beta-cell proliferation and regeneration after beta-cell injury.
Moreover, by altering their activation state, macrophages are able to improve
insulin resistance in murine models of T2D. This review will elaborate on current
insights in macrophage heterogeneity and on the evolving role of pancreas
macrophages during organogenesis, tissue injury, and repair. Additional
identification of macrophage subtypes and of their secreted factors might
ultimately translate into novel therapeutic strategies for both T1D and T2D.
SIGNIFICANCE: Diabetes mellitus is a pandemic disease, characterized by severe
acute and chronic complications. Macrophages have long been considered prime
suspects in the pathogenesis of both type 1 and 2 diabetes mellitus. In this
concise review, current insights in macrophage heterogeneity and on the, as yet,
underappreciated role of alternatively activated macrophages in insulin sensing
and beta-cell development/repair are reported. Further identification of
macrophage subtypes and of their secreted factors might ultimately translate into
novel therapeutic strategies for diabetes mellitus.
PMID- 25848126
TI - Development and Validation of the Spiritual Care Needs Inventory for Acute Care
Hospital Patients in Taiwan.
AB - Spiritual care is increasingly being recognized as an integral aspect of nursing
practice. The aim of this study was to develop a new instrument, Spiritual Care
Needs Inventory (SCNI), for measuring spiritual care needs in acute care hospital
patients with different religious beliefs. The 21-item instrument was completed
by 1,351 adult acute care patients recruited from a medical center in Taiwan.
Principal components analysis of the SCNI revealed two components, (a) meaning
and hope and (b) caring and respect, which together accounted for 66.2% of the
total variance. The internal consistency measures for the two components were
0.96 and 0.91, respectively. Furthermore, younger age, female sex, Christian
religion, and regularly attending religious activities had significantly higher
mean total scores in both components. The SCNI was found to be a simple
instrument with excellent internal consistency for measuring the spiritual care
needs in acute care hospital patients.
PMID- 25848127
TI - Effect of Acupressure on Maternal Anxiety in Women With Gestational Diabetes
Mellitus: A Randomized Clinical Trial.
AB - Women with diabetes often experience a higher level of anxiety. The aim of the
study was to evaluate the effect of acupressure on relieving anxiety of women
with gestational diabetes mellitus (GDM). A randomized clinical trial was
conducted on 60 women with GDM at a university hospital. The participants were
allocated to an experimental and a placebo group (30 women per group). The
experimental group received a nurse-provided acupressure at the true point, and
the placebo group received pressure (touching) at a sham (false) point. Anxiety
was measured immediately in the groups prior to and after a 2-day intervention by
a questionnaire and the Visual Analogue Scale. The data were analyzed using
descriptive and inferential statistics. Results indicated that the acupressure
group had significantly lower anxiety than the placebo group (p <= .0001). In
conclusion, the effects of acupressure appeared to be effective in reducing
anxiety in diabetic pregnant women.
PMID- 25848129
TI - Streptococcus pneumoniae-Associated Hemolytic and Uremic Syndrome With
Cholestasis: A Case Report and Brief Literature Review.
PMID- 25848128
TI - Correlates of Human Papillomavirus Vaccine Completion Among Adolescent Girl
Initiators.
AB - OBJECTIVE: To examine correlates of vaccine series completion among young
adolescent US girls who initiated the human papillomavirus (HPV) vaccine.
METHODS: We analyzed National Immunization Survey-Teens 2012 provider-verified
data to examine correlates of HPV vaccine completion among 13- to 17-year-old
girls who initiated HPV vaccine in 2012 (N = 4548). RESULTS: The weighted vaccine
series completion rate among 13- to 17-year-old girl initiators was 66.7% (95%
confidence interval [CI], 64.0-69.3). Adolescent girls who were older, residents
of the Northeast (adjusted prevalence ratio [aPR], 1.36; 95% CI, 1.07-1.73), and
had provider-verified seasonal influenza vaccination in the past year (aPR, 1.67;
95% CI, 1.32-2.11) and provider recommendation (aPR, 1.40; 95% CI, 1.10-1.77)
were more likely to complete the 3-dose vaccine series. CONCLUSIONS: Parents of
younger adolescent girls need to be educated about the importance of completing
the 3-dose HPV vaccine series. Provider recommendation for the vaccine would also
facilitate series completion.
PMID- 25848130
TI - Failure to Thrive and Respiratory Failure in an Adolescent Male.
PMID- 25848131
TI - Effects of Rivaroxaban on Platelet Activation and Platelet-Coagulation Pathway
Interaction: In Vitro and In Vivo Studies.
AB - INTRODUCTION: Activation of coagulation and platelets is closely linked, and
arterial thrombosis involves coagulation activation as well as platelet
activation and aggregation. In these studies, we investigated the possible
synergistic effects of rivaroxaban in combination with antiplatelet agents on
thrombin generation and platelet aggregation in vitro and on arterial thrombosis
and hemostasis in rat models. MATERIALS AND METHODS: Thrombin generation was
measured by the Calibrated Automated Thrombogram method (0.5 pmol/L tissue
factor) using human platelet-rich plasma (PRP) spiked with rivaroxaban (15, 30,
or 60 ng/mL), ticagrelor (1.0 ug/mL), and acetylsalicylic acid (ASA; 100 ug/mL).
Tissue factor-induced platelet aggregation was measured in PRP spiked with
rivaroxaban (15 or 30 ng/mL), ticagrelor (1 or 3 ug/mL), or a combination of
these. An arteriovenous (AV) shunt model in rats was used to determine the
effects of rivaroxaban (0.01, 0.03, or 0.1 mg/kg), clopidogrel (1 mg/kg), ASA (3
mg/kg), and combinations on arterial thrombosis. RESULTS: Rivaroxaban inhibited
thrombin generation in a concentration-dependent manner and the effect was
enhanced with ticagrelor and ticagrelor plus ASA. Rivaroxaban and ticagrelor also
concentration-dependently inhibited tissue factor-induced platelet aggregation,
and their combination increased the inhibition synergistically. In the AV shunt
model, rivaroxaban dose-dependently reduced thrombus formation. Combining
subefficacious or weakly efficacious doses of rivaroxaban with ASA or ASA plus
clopidogrel increased the antithrombotic effect. CONCLUSION: These data indicate
that the combination of rivaroxaban with single or dual antiplatelet agents works
synergistically to reduce platelet activation, which may in turn lead to the
delayed/reduced formation of coagulation complexes and vice versa, thereby
enhancing antithrombotic potency.
PMID- 25848132
TI - Effects of Pregnane X Receptor Genetic Polymorphisms on Stable Warfarin Doses.
AB - OBJECTIVE: Pregnane X receptor (PXR) is a transcriptional regulator of many drug
metabolizing enzymes including cytochrome P450 (CYP) 2C9. The objective of this
study was to assess the possible association between PXR single-nucleotide
polymorphisms (SNPs) and stable warfarin doses. METHODS: A total of 201 patients
with stable warfarin doses from the EwhA-Severance Treatment (EAST) Group of
Warfarin were included in this study. The influence of genetic polymorphisms on
stable warfarin doses was investigated by genotyping 11 SNPs, that is, vitamin K
epoxide reductase complex 1 (VKORC1) rs9934438, CYP2C9 rs1057910, CYP4F2
rs2108622, constitutive androstane receptor (CAR) rs2501873, hepatocyte nuclear
factor 4alpha (HNF4alpha) rs3212198, and PXR (rs3814055, rs1403526, rs3732357,
rs3732360, rs2276707 and rs2472682). Subgroup analysis was conducted on CYP2C9
wild-type homozygote allele (AA) carriers. RESULTS: One PXR SNP of rs2472682
(A>C) exhibited significant association with stable warfarin doses in study
population and the subgroup; variant homozygote carriers required significantly
lower daily doses of warfarin than those carrying wild allele by about 0.8 mg.
Approximate 43.7% of overall interindividual variability in warfarin dose
requirement was explained by multivariate regression model. VKORC1, CYP2C9, age,
CYP4F2, PXR rs2472682, and CAR/HNF4alpha rs2501873/rs3212198 accounted for 29.6%,
5.9%, 3.7%, 2.3%, 1.3%, and 0.9% of the variability, respectively. PXR SNP of
rs2472682 remained a significant factor in CYP2C9 wild-type homozygote carriers
based on univariate and multivariate analyses. The combination of
CAR/HNF4alpha/PXR SNPs of rs2501873/rs3212198/rs2472682 showed about 1 mg dose
difference between grouped genotypes in study population and subgroup.
CONCLUSION: Our results revealed that PXR could be a determinant of stable
warfarin doses.
PMID- 25848133
TI - First Metatarsophalangeal Joint Arthrodesis Technique With Interposition
Allograft Bone Block.
AB - BACKGROUND: We present a technique of first metatarsophalangeal joint arthrodesis
utilizing an interposition allograft bone block with a bipolar reaming technique
that creates congruent fusion surfaces on both ends of the graft-host bone
interface. In addition, we examined the union rates, fusion position, patient
satisfaction, and functional outcome of this technique. METHODS: Fifteen patients
underwent first metatarsophalangeal joint arthrodesis with an interposition
allograft bone block between September 2004 and October 2013. Charts and
radiographs were reviewed. Six measures were compared on preoperative and
postoperative radiographs. Clinical outcomes were measured using a telephone
questionnaire, pre- and postoperative visual analog scale pain scale, and Foot
and Ankle Ability Measure. Average follow-up was 46 weeks (range, 19 to 97).
RESULTS: Thirteen of 15 (87%) patients achieved bony union at an average of 21
weeks. One patient underwent revision arthrodesis for their nonunion. Symptomatic
hardware was removed in 3 cases. Improvement was noted in visual analog scale
pain scores (6 to 2) and functional scores as measured by the Foot and Ankle
Ability Measure. There were no postoperative wound complications or infections.
Average length of the first ray on anteroposterior radiograph increased from 10.7
to 11.3 cm and from 10.0 to 10.7 cm on the lateral radiograph. Thirteen of 14
patients were very satisfied or satisfied. One patient expressed dissatisfaction
with the procedure. One patient was not available for clinical follow-up.
CONCLUSION: First metatarsophalangeal joint allograft bone block arthrodesis
using the bipolar reaming technique achieved high bony union rates and
satisfactory radiographic and clinical outcomes. This procedure was an effective
salvage option for managing bone loss on 1 or both sides of the joint. LEVEL OF
EVIDENCE: Level IV, retrospective case series.
PMID- 25848134
TI - Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated
With rhPDGF-BB in Combination With a beta-TCP-Collagen Matrix.
AB - BACKGROUND: Ankle and hindfoot arthrodesis is often supplemented with autograft
to promote bony union. Autograft harvest can lead to increased perioperative
morbidity. Purified recombinant human platelet-derived growth factor BB homodimer
(rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot
fusion. This randomized controlled trial evaluated the efficacy and safety of
rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate
(beta-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions.
METHODS: Seventy-five patients requiring ankle or hindfoot fusion were randomized
5:1 for rhPDGF-BB/beta-TCP-collagen (treatment, n = 63) or autograft (control, n
= 12). Prospective analysis included 142 autograft control subjects from another
clinical trial with identical study protocols. Standardized operative and
postoperative protocols were used. Patients underwent standard internal fixation
augmented with autograft or 0.3 mg/mL rhPDGF-BB/beta-TCP-collagen. Radiologic,
clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary
outcome was joint fusion (50% or more osseous bridging on computed tomography) at
24 weeks. Secondary outcomes included radiographs, clinical healing status,
visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle
Hindfoot Scale score, Foot Function Index score, and Short Form-12 score.
Noninferiority P values were calculated. RESULTS: Complete fusion of all involved
joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63
(84%) rhPDGF-BB/beta-TCP-collagen-treated patients and 100 of 154 (65%) autograft
treated patients (P < .001). Mean time to fusion was 14.3 +/- 8.9 weeks for
rhPDGF-BB/beta-TCP-collagen patients versus 19.7 +/- 11.5 weeks for autograft
patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%)
rhPDGF-BB/beta-TCP-collagen patients and 120 of 154 (78%) autograft patients (P <
.001). Safety-related outcomes were equivalent. Autograft controls had 2 bone
graft harvest infections. CONCLUSIONS: Application of rhPDGF-BB/beta-TCP-collagen
was a safe, effective alternative to autograft for ankle and hindfoot fusions,
eliminating the pain and morbidity associated with autograft harvesting. LEVEL OF
EVIDENCE: Level I, prospective randomized study.
PMID- 25848135
TI - Tibiotalocalcaneal Arthrodesis With an Intramedullary Hindfoot Nail and Pillar
Fibula Augmentation: Technical Tip.
PMID- 25848136
TI - Age and residency duration of loggerhead turtles at a North Pacific bycatch
hotspot using skeletochronology.
AB - For migratory marine animals, like sea turtles, effective conservation can be
challenging because key demographic information such as duration of life stages
and exposure to spatially explicit threats in different habitats are often
unknown. In the eastern Pacific near the Baja California Peninsula (BCP), Mexico,
tens of thousands of endangered North Pacific loggerhead sea turtles (Caretta
caretta) concentrate at a foraging area known to have high rates of fishery
bycatch. Because stage survivorship of loggerheads in the BCP will vary
significantly depending on the number of years spent in this region, we applied
skeletochronology to empirically estimate residency duration in this loggerhead
hotspot. The observed age distribution obtained from skeletochronology analysis
of 146 dead-stranded loggerheads ranged from three to 24 years old, suggesting a
BCP residency of >20 years. Given the maximum estimated age and a one-year
migration to western Pacific nesting beaches, we infer age-at-maturation for BCP
loggerheads at ~25 years old. We also examine survivorship at varying BCP
residency durations by applying our findings to current annual mortality
estimates. Predicted survivorship of loggerheads spending over 20 years in this
BCP foraging habitat is less than 10%, and given that ~43,000 loggerhead turtles
forage here, a significant number of turtles are at extreme risk in this region.
This is the first empirical evidence supporting estimated age-at-maturation for
BCP North Pacific loggerheads, and the first estimates of BCP stage survivorship.
Our findings emphasize the urgent need for continued and effective international
conservation efforts to minimize bycatch of this endangered species.
PMID- 25848138
TI - A Method to Determine the Density of Foods using X-ray Imaging.
AB - Density of foods is an important physical property, which depends on structural
properties of food. For porous foods such as baked foods, accurate measurement of
density is challenging since traditional density measurement techniques are
tedious, operator-dependent and incapable of precise volume measurement of foods.
To overcome such limitations, a methodology was developed using both digital
radiography(DR) and computed tomography(CT) x-ray imaging to directly determine
density of foods. Apparent density was determined directly from x-ray linear
attenuation coefficients by scanning at 40, 60, 80 kVp on DR and 45, 55, 70 kVp
on CT. The apparent density can be directly determined using CT however sample
thickness is needed to determine density using DR. No significant difference
(p<0.05) was observed between density obtained from traditional methods, with
density determined from x-ray linear attenuation coefficients. Density determined
on CT for all foods with mean 0.579 g/cm3 had a standard deviation, SD = 0.0367
g/cm3. Density determination using x-ray linear attenuation was found to be a
more efficient technique giving results comparable with conventional techniques.
PMID- 25848137
TI - Wrinkled, wavelength-tunable graphene-based surface topographies for directing
cell alignment and morphology.
AB - Textured surfaces with periodic topographical features and long-range order are
highly attractive for directing cell-material interactions. They mimic
physiological environments more accurately than planar surfaces and can
fundamentally alter cell alignment, shape, gene expression, and cellular assembly
into superstructures or microtissues. Here we demonstrate for the first time that
wrinkled graphene-based surfaces are suitable as textured cell attachment
substrates, and that engineered wrinkling can dramatically alter cell alignment
and morphology. The wrinkled surfaces are fabricated by graphene oxide wet
deposition onto pre-stretched elastomers followed by relaxation and mild thermal
treatment to stabilize the films in cell culture medium. Multilayer graphene
oxide films form periodic, delaminated buckle textures whose wavelengths and
amplitudes can be systematically tuned by variation in the wet deposition
process. Human and murine fibroblasts attach to these textured films and remain
viable, while developing pronounced alignment and elongation relative to those on
planar graphene controls. Compared to lithographic patterning of nanogratings,
this method has advantages in the simplicity and scalability of fabrication, as
well as the opportunity to couple the use of topographic cues with the unique
conductive, adsorptive, or barrier properties of graphene materials for
functional biomedical devices.
PMID- 25848139
TI - Extensive complex odontoma in the maxillary sinus pushing 3rd molar near the
orbital floor causing transient diplopia and chronic sinusitis: a rare
presentation and surgical management.
AB - Odontoma is a mixed odontogenic hamartoma involving both epithelial and
mesenchymal tissues. If left untreated, it can lead to complications in certain
conditions. Here is a rare presentation of an extensive complex odontoma in
maxillary sinus pushing third molar near the orbital floor causing transient
diplopia in upward gaze occasionally and chronic sinusitis. Although odontomata
are not uncommon and are familiar to practitioners, but some aggressive cases may
cause problematic sequelae. Even postoperative complications may result if oral
surgeons are not aware of the potential pitfalls associated with the surgical
removal of large maxillary antrum odontomata. This article reports a rare
presentation which can be considered unique because when obstruction of sinus
drainage is evident, serious complications such as orbital infections, epidural
and subdural empyema, meningitis, cerebritis, cavernous sinus thrombosis, brain
abscess and death can occur. It also addresses points and pitfalls concerning
surgery to remove odontoma.
PMID- 25848140
TI - 'Potato peel dressing': a novel adjunctive in the management of necrotizing
fasciitis.
AB - Management of necrotizing fasciitis, a rare and potentially fatal, polymicrobial
disease comprises of aggressive debridement, intravenous antibiotics and
application of various adjunctives. So far adjunctives like hyperbaric oxygen
therapy, intravenous immunoglobulins, vacuum assisted or foam dressing, and
guided tissue regeneration with amniotic dressing have been put to use. Each of
these adjunctives has faced criticism for their shortcomings. Potato peel has
been used as a dressing for chronic wounds but there is no literature available
on its application over wounds afflicted with necrotizing fasciitis. Owing to
various medicinal properties of potato peel and its use as a dressing in other
medical conditions, same was used as an adjunctive in the present case. Here we
present a case of cervical necrotizing fasciitis of dentogenous origin, treated
by mainstay surgical treatment with debridement, drainage in combination with
broad spectrum antibiotics and a novel adjunctive, 'potato peel dressing', which
has shown promising results.
PMID- 25848141
TI - Potentially fatal supramylohyoid sublingual epidermoid cyst.
AB - A case of chronic and slow growing massive lateral neck swelling is presented
which gradually resulted in dysphagia to an extent that patient reported in
emergency room. Clinical findings were indicative of a cystic swelling or a
massive lipoma. Temporary decompression of the lesion was achieved by partially
aspirating the contents of the cyst. Nature of aspirate and its microscopic and
biochemical analysis excluded lipoma, vascular malformation and salivary
phenomenon. The diagnosis tapered to developmental lateral neck cysts. Magnetic
Resonance Imaging (MRI) revealed a massive cystic lesion in the left floor of
mouth extending to the right lingual aspect of mandible and posteriorly to
impinge on the medial wall of pharynx. A combined intraoral and extraoral
approach was used to expose and excise the lesion in toto. Final histological
diagnosis of the pathology was epidermoid cyst.
PMID- 25848142
TI - Eagle's Syndrome: A New Surgical Technique for Styloidectomy.
AB - The purpose of this paper is to discuss the current diagnosis of Eagle's syndrome
(elongated styloid process) and to discuss a new and a much simpler technique for
styloidectomy with an intraoral approach which can be used in local anesthesia.
Easiness to perform, non-association of any anesthetic complications and
avoidance of an extraoral scar dictates that this approach can be practiced much
safely in patients with elongated styloid process.
PMID- 25848143
TI - Hemiatrophy of the tongue caused by an extensive vagus nerve schwannoma
masquerading as a carotid chemodectoma.
AB - BACKGROUND: Carotid chemodectomas or carotid body tumors are rare neoplasms,
generally benign and frequently asymptomatic, which represent 0.6 % of all head
and neck tumours. Schwannomas or neurilemmomas are benign, slow growing tumours
that derive from the sheath of peripheral and cranial nerves. Of all
neurilemmomas, 25-45 % originate from the head and neck region, with the vagus
nerve being one the most encountered sites of occurrence. CASE REPORT: We
describe a schwannoma originating from the vagus nerve mimicking a carotid body
tumour and compromising the function of the hypoglossal nerve. DISCUSSION:
Patients with lateral neck masses near the bifurcation of the carotid artery are
often referred to the maxillofacial surgeon. The differential diagnosis of these
lesions includes a variety of tumours among which carotid chemodectomas and vagus
nerve schwannomas have a significant incidence. Both lesions may appear as
completely asymptomatic, thus it is very difficult to identify the origin of the
tumour based on physical examination. In making a differential diagnosis of the
cervical tumours imaging studies play a key role. PURPOSE: A diagnostic algorithm
based on contemporary imaging modalities, which can be useful in order to
distinguish between these two pathological entities is presented.
PMID- 25848144
TI - Collision tumor of maxilla: a diagnostic dilemma.
AB - Most malignant tumors arise from the primary tissue except when showing extreme
dedifferentiation. This can be identified by examination of tumor cells and their
products. Occasionally two distinct tissues are recognized within a malignant
tumor. In mixed malignant tumors both carcinomatous and sarcomatous elements are
present either because of simultaneous malignant change occurring in the
epithelium and its nonepithelial stroma or there is a sarcomatous transformation
of stroma of a carcinoma. Willey's in 1960 stated that in these circumstances the
resulting tumor must be classified as a "carcino-sarcoma". These separate tumors
arise in nearby structures and may grow to infiltrate in each other resulting in
a tumor mass. The present article is a report of a diagnostic dilemma in an
extremely rare carcinosarcoma of maxilla in a 24 year old male which was first on
biopsy reported as odontogenic myxoma. After resection (right maxillectomy under
GA using Weber Fergusons approach with Diffenbach's extension) was diagnosed as
Squamous Cell Carcinoma arising from lining of the maxillary antrum associated
with Osteogenic Sarcoma (chondroblastic differentiation) of maxilla with negative
margins. The tumor was restaged to T2NoMx and further managed as per National
Comprehensive Cancer Network Guidelines. Immunohistochemistry later re-diagnosed
it to be an Osteogenic Sarcoma maxilla with chondroblastic differentiation. 'T'
stage remains the most reliable predictor of survival and loco-regional control.
Complete surgical resection for all 'T' stages (except T4b, any N) followed by
postoperative therapy remains a corner stone of treatment of maxillary sinus
tumors.
PMID- 25848145
TI - Tissue expanders in reconstruction of maxillofacial defects.
AB - Tissue expansion in its natural ways had fascinated man from prehistoric times
itself. But tissue expansion for medical purposes was first tried and reported
only in the early half of twentieth century. Presently the principle of tissue
expansion is being used in reconstruction of many hard and soft tissue defects of
larger dimension, which were previously regarded as great challenge for
maxillofacial and plastic surgeons. Making use of the viscoelastic nature of the
skin, considerable amount of tissue expansion based tissue engineering is
possible in the maxillofacial region. Here we present a case of a facial scar of
large dimension with a central oro cutaneous fistula developed as a result of
facial artery blow out in a 24 year old female for which esthetic correction was
done using the excess tissue obtained from tissue expansion. In this case where
other methods of reconstruction such as local flaps, free flaps and normal tissue
grafts were assessed to be non viable, tissue expansion was found to be an apt
solution for esthetic reconstruction.
PMID- 25848146
TI - Amniotic membrane as a biological scaffold after vestibuloplasty.
AB - Vestibuloplasty techniques are widely carried out to make the denture bearing
area more suitable and adequate to receive the intended prosthesis. One of the
major challenges after a vestibuloplasty procedure is to reduce post operative
discomfort, scar contracture and subsequent loss in sulcular depth. A raw bony
surface, as is obtained after Clark's vestibuloplasty is prone not only to
infections and increased pain, but also to increased scarring during the healing
phase. Skin grafts have been most commonly used to cover the exposed periosteal
surface but they have their own disadvantages. There is a constant search for
biocompatible membranes/materials which would satisfy most criteria required of a
biological scaffold. Amnion is the innermost layer of the placenta with certain
unique properties. Here we discuss the efficacy of amniotic membrane as a
biological dressing after vestibuloplasty.
PMID- 25848147
TI - Sicca syndrome and dementia in a patient with hepatitis C infection: a case
report with unusual bifocal extrahepatic manifestations.
AB - INTRODUCTION: Hepatitis C virus (HCV) infections are associated with extrahepatic
manifestations in 40-75 % of cases. Sialitis and secondary Sjogren syndrome are
well characterized complications of chronic HCV infections but the mechanisms
(primary or secondary) leading to xerostomia are not understood. Similarly, brain
lesions due to HCV can be primary or secondary but the pathology of primary HCV
related brain lesions is not well described. CASE REPORT: We report the
postmortem case of a 60-year old patient initially presenting with sicca syndrome
and dementia. HCV was identified in the brain but not in the salivary glands
using transcription-mediated amplification (TMA). Focal sialitis was found in
submandibular glands. Neuropathological examination revealed the presence of
multiple dot-sized demyelination foci. CONCLUSION: Sicca syndrome is a common
concern in chronic HCV infections and may be due to secondary immune mechanisms
(we could not isolate HCV in salivary gland tissues). TMA had never been applied
to the detection of viruses in salivary glands and neural tissues and proves to
be a promising technique. Neuropathological reports in HCV infections are rare
and the lesions we report may be the first characterization of the direct effect
of HCV on brain cells. More cases are needed to define the full spectrum of
lesions potentially caused by the direct action of the HCV on salivary glands and
neural tissues.
PMID- 25848148
TI - Multiple verrucous carcinomas of the oral cavity.
AB - The author herein reports a case of multiple verrucous carcinomas (VCs) of the
left lower gingiva. A 78-year-old man was admitted to our hospital because of
gingival tumor. A biopsy revealed severe dysplasia. Surgical resection was
performed. Grossly, there were three verrucous lesions (25, 20, 10 mm) in the
left lower gingiva. Histologically, 2 tumors (4, 2 mm) were found in addition to
the grossly visible 3 tumors. All the 5 tumors were VCs. The tumors showed
verrucous and papillary proliferation of squamous epithelium with little cellular
atypia. No invasive features were recognized. The dermis showed lymphocytic
infiltration. The surrounding mucosa showed many broad foci of squamous cell
carcinoma in situ and severe dysplasia (high grade intraepithelial neoplasm).
Gradual merges between the VCs and squamous cell carcinoma in situ or severe
dysplasia were frequently recognized. Immunohistochemically, the VC tumor cells
and squamous lesions were negative for human papilloma virus antigens. P53
protein was expressed in all the VCs and squamous epithelial lesions: it was
accentuated in the basal and suprabasal cells of VC. Ki-67 antigen was also
expressed in the 5 VCs and in the squamous lesion, and Ki-67 labeling index
ranged from 8 to 16 % in VC and from 37 to 62 % in the squamous lesions. These
data support the multicentric nature of VC and that the severe dysplasia
carcinoma in situ sequence have been proposed in the etiology of VC.
PMID- 25848149
TI - Vascular transformation of bilateral cervical lymph node sinuses: a rare entity
masquerading as tumor recurrence.
AB - Vascular transformation of sinuses (VTS) is a rare and reactive vasoproliferative
disorder infrequently affecting the cervical lymph nodes. It is characterized by
effacement of nodal architecture by variable expansion of the subcapsular,
intermediate, and medullary sinuses. We report a very rare and unique case of VTS
in bilateral cervical lymph nodes along with angiolipomatous hamartoma in a
postoperative patient of squamous cell carcinoma of buccal mucosa clinically
masquerading as tumor recurrence. To the best of our knowledge, only 15 cases of
VTS have been reported in cervical lymph nodes till date and associated
angiolipomatous or angiomyomatous hamartoma-like area was noted only in two cases
of cervical lymph node VTS.
PMID- 25848150
TI - Giant osteochondroma of the coronoid process.
AB - Osteochondroma or solitary osteocartilagenous exostosis is characterized by
cartilage-capped osseous lesion, protruding from the surface of affected bone. It
is one of the most common benign bone tumor in axial skeleton and infrequent in
maxillofacial skeleton. This paper describes a giant osteochondroma of coronoid
process in a 20 year old woman, presented with limited mouth opening (15 mm inter
incisal distance) and pain without any facial swelling, asymmetry and TMJ
problems. Based on clinical examination, panoramic radiography and computed
tomography images a provisional diagnosis of osteoma or osteochondroma of the
coronoid process was made. Under general anaesthesia through intra oral approach
excision of the bony tumor along with the coronoid process was performed, with
recovery of mouth opening up to 40 mm immediately following surgery. The
histopathology of excised specimen revealed features suggestive of
osteochondroma. After follow up period of 54 months patient is symptom free. Here
we are presenting and discussing the complete diagnostic and treatment aspect of
this unusually large osteochondroma of coronoid process of mandible.
PMID- 25848151
TI - Pseudotumour of the Mandible Associated with von Willebrand's Disease.
AB - Patients with bleeding disorders may occasionally present with pseudotumours.
Most commonly these occur in the soft tissues and long bones, and are very rare
in the maxillofacial region. We present the clinical details and management of a
pseudotumour of the mandible in a 12-year-old girl with von Willebrand's disease.
PMID- 25848152
TI - The karapandzic flap in lower lip reconstruction.
AB - Human bite injuries are both deceptive and challenging in their presentation and
management. They are particularly notorious due to the polymicrobial nature of
human saliva inoculated in the wound and the risk they pose for transmission of
infectious diseases. Early treatment, appropriate prophylaxis and surgical
evaluation are the key to achieving desired treatment outcomes. Here we present a
case report of human lip bite with significant tissue loss that required
reconstruction. The reconstructive techniques are usually varied but the ultimate
objectives of treatment are to achieve healing, function, and aesthetics. Through
this article, we have tried to focus on the diagnostic features, reconstructive
procedure as well as other recommended treatment options for human lip bites
based on the current available evidence.
PMID- 25848153
TI - Traumatic herniation of buccal fat pad in 1 year old child: case report and
review of literature.
AB - Traumatic herniation of buccal fat pad (BFP) is very rare, usually seen in
infants and young children ranging from 5 months to 12 years of age. Etiology
will be blunt injury to buccal mucosa from foreign objects or trauma due to teeth
and fall. The suckling activity in infants may also encourage the herniation
following trauma. A minor injury or perforation to the buccal mucosa can cause
herniation of BFP. The size of herniated mass is very large when compared to the
size of the perforation. The history of trauma, absence of prolapse before the
injury, its occurrence in infants and young children, specific anatomic sites and
location of perforation in mucosa, histopathological appearance of adipose tissue
are the characteristic features important for diagnosing the condition. The
treatment options for the herniated BFP are usually excision. Alternative to
excision is repositioning of the herniated fat in its anatomical location if
noticed early.
PMID- 25848154
TI - Salivary gland tumors: a diagnostic dilemma!
AB - Salivary gland tumors generate considerable interest because of their
heterogeneous and variable histology, grade of malignancy, and clinical behavior.
Fine needle aspiration cytology (FNAC) is considered the first diagnostic
modality for salivary neoplasms due to its ready availability and ease of
performance. However it cannot always be relied upon in isolation, and should be
used in conjunction with other investigations like incisional biopsy. We present
two cases, which highlight the drawbacks of relying on FNAC alone, which resulted
in misdiagnosis of adenoid cystic carcinoma as pleomorphic adenoma.
PMID- 25848155
TI - Bilateral glandular odontogenic cyst of mandible: a rare occurrence.
AB - Glandular odontogenic cysts (GOCs) of the jaw are rare with well-defined limits
radiologically, unusual histopathological features and a high recurrence rate.
The radiographic appearance of GOCs vary and are not pathognomonic. Definitive
diagnosis of the GOC is established only by histopathological examinations.
Histologically, GOC is characterized by a thin nonkeratinized squamous epithelial
lining, with papillary projections, nodular thickenings, mucous (goblet) cells
with intraepithelial mucous pools and intraepithelial glandular, microcystic or
duct-like structures. We present an unusual case of a bilateral GOC in the
mandible. This case report is also the first documented case of bilateral GOC in
the mandible.
PMID- 25848156
TI - A Case of Oro-antral Communication Closed by Autotransplantation of Third Molar.
AB - A number of surgical treatment modalities have been described in literature for
closure of oro-antral communications. None of the methods however provide for
immediate prosthetic rehabilitation of the communication site. We describe a case
of oro-antral communication treated using autogenous third molar transplantation.
At 18 months of follow-up, the transplanted tooth was functioning well with
radiographic evidence of lamina dura and periodontal ligament. Its root-tip was
still seen projecting into the maxillary sinus. This report suggests that when
possible, autotransplantation of third molar can be a simple and excellent choice
for closure of oro-antral communications.
PMID- 25848157
TI - Recurrence of a giant peripheral osteoma of mandible.
AB - Osteomas are rare benign tumours in the bone. We describe a case of giant osteoma
involving the lingual side of the ramus and body of mandible that recurred 8
years after its surgical treatment at another hospital. Surgical resection with
reconstruction is the treatment of choice for this lesion. The
clinicopathological features of osteoma are discussed and Gardner's syndrome was
excluded.
PMID- 25848158
TI - Septo-optic Dysplasia Complex with Omphalocele, Pre-maxillary Agenesis and
Encephalocele.
AB - Septo-optic dysplasia complex (SODC) is a rare congenital anomaly, characterized
with absence of septum pellucidum, optic nerve hypoplasia with or without
pituitary dysfunction. Various midline defects are also associated with SODC in
addition to its classical findings. We report, for the first time a rare
presentation of SODC which is associated with pre-maxillary agenesis along with
sphenoidal encephalocele and omphalocele. The case showed resulting median cleft
lip and palate along with other multiple congenital defects including hydrocele,
inguinal hernia, micropenis and a wide mediastinum.
PMID- 25848159
TI - MRI as an essential diagnostic approach for trigeminal neuralgia.
AB - Trigeminal neuralgia is a well recognised disorder frequently reported to the
dentist. The diagnosis of trigeminal neuralgia is primarily based on history and
clinical criteria. The clinical findings do not differentiate idiopathic
trigeminal neuralgia from symptomatic trigeminal neuralgia. We describe a case of
cliviopetrosal meningioma presenting as trigeminal neuralgia and discuss the
importance of magnetic resonance imaging as an essential diagnostic approach when
trigeminal neuralgia occurs concurrently with a brain tumour.
PMID- 25848160
TI - Neurofibroma of facial nerve presenting as parotid mass.
AB - Neurogenic neoplasms presenting as parotid gland tumors are extremely uncommon.
We present the case of a solitary neurofibroma of the facial nerve within the
parotid gland occurring in a 36-year-old male who presented with a painless
enlargement in the right-side region of the parotid gland over a period of 1 year
with normal facial nerve function. Magnetic resonance imaging revealed a well
demarcated round mass within the right parotid. At surgery, a tumor was found
involving the main trunk of the facial nerve, histopathologically representing a
neurofibroma.
PMID- 25848161
TI - Conservative treatment protocol of keratocystic odontogenic tumor: report of a
case with nevoid Basal cell carcinoma syndrome and literature review.
AB - Keratocystic odontogenic tumor (KOT) is one of the major components of nevoid
basal cell carcinoma syndrome (NBCCS), which usually occurs in young ages and
includes significant structures of jaws. According to high recurrence rate of
KOT, there are many controversies in treatment of the lesion, especially in
syndromic cases with younger ages. In current report, authors suggest a
conservative protocol in the treatment of KOT in a patient with NBCCS.
PMID- 25848162
TI - Facial translocation approach for management of invasive sinonasal aspergillosis.
AB - Aspergillosis is an uncommon fungal disease seen commonly in paranasal sinuses.
It may be of noninvasive variety which is restricted to paranasal sinuses seen in
healthy and immunocompetent hosts or may present as invasive form seen in
immunocompromised hosts especially in diabetics and patients under long term
immunosuppressant therapy. Along with paranasal sinuses invasive forms may
encroach upon surrounding adjacent structures involving the orbit and extend
intracranially. Orbital and intracranial involvement have a high mortality rate.
Early diagnosis of the lesion and prompt aggressive management is important for
better prognosis. Aggressive treatment includes surgical debulking and medical
management mainly with systemic amphotericin B and other azoles. In orbito
cranial involvement, due to limited access to cranial base, it becomes difficult
to surgically debulk the lesion with safety to surrounding important structures.
Facial translocation approach gives adequate access to paranasal sinuses, orbit
and anterior cranial base. Reported here are two cases of invasive cranio-orbito
nasal aspergillosis treated with facial translocation approach.
PMID- 25848163
TI - Challenges in Health Research Funding: an opinion.
PMID- 25848164
TI - Neutralization function affected by single amino acid replacement in the HIV-1
antibody targets.
AB - The viral envelope glycoproteins are essential for entry into their host cells
and studied extensively for designing vaccines. We hypothesize that the
glycosylation on the HIV-1 viral envelope glycoprotein 41(gp41) at critical
residues offers viral escape from the specific immune surveillant neutralizing
antibodies Z13, 4E10 and 10E8 targeted to their linear epitopes in the Membrane
Proximal External Region (MPER). The glycosylation occurring on the 50th residue
(Asparagine) contained in the target (NWFNIT) can mask itself to be inaccessible
for these neutralizing antibodies. The glycosylation rate of the epitopes which
are shared by the Z13, 4E10 and 10E8 neutralizing antibodies of HIV-1 were
predicited in silico. We analyzed the reliable frequency of glycosylation on the
HIV-1 envelope gp41 using prediction tools to unravel the plausibility of the
glycosylation by a mannose at 50th residue in the 59 amino acid long HIV-gp41
trimer (PDBID: 2M7W and 2LP7). It is evident that the glycosylation by a mannose
that masks these targets is possible only when the 50th amino-acid is N
(Asparagine, Asn) which is not possible when N is mutated to D (Aspartatic acid,
Asp). The additive advantage for the retrovirus is its error-prone reverse
transcriptase which can choose to copy these survivable mutants with Asn N-50
that can be glycosylated as explained by the Copy-choice model. So the glycan
shields varying in their intensity and patterns have to be essentially studied to
understand the viral escape strategies that will give a way forward towards a
successful vaccine that can elicit a neutralizing antibody response to confer
protection.
PMID- 25848165
TI - Pharmacophore elucidation and molecular docking studies on phosphodiesterase-5
inhibitors.
AB - cGMP-binding cGMP-specific PDE, PDE5 plays a key role in the hydrolysis of cyclic
guanidine monophosphate. Because cGMP mediates vascular functions, a PDE5
inhibitor that elevates cGMP level is an attractive means for vasodilatation and
treatment of erectile dysfunction. In this paper we report the elucidation of the
common pharmacophore hypothesis of different classes of PDE5 inhibitors. Using
LigandScout program, pharmacophore modelling studies were performed on prior
reported potent PDE5 inhibitors with a variety of scaffolds in order to identify
one common set of critical chemical features of these PDE5 inhibitors 1-52. The
best pharmacophore model, model-1, characterized by four chemical features: one
aromatic ring, one hydrophobe, one hydrogen acceptors and one hydrogen donor.
Using Dock6 program, docking studies were performed in order to investigate the
mode of binding of these compounds. The molecular docking study allowed
confirming the preferential binding mode of different classes of PDE5 inhibitors
inside the active site. The obtained binding mode was as same as that of
vardenafil, X-ray ligand with different orientation with varied PDE5 inhibitors'
scaffold.
PMID- 25848166
TI - Comparative sequence-structure analysis of Aves insulin.
AB - Normal blood glucose level depends on the availability of insulin and its ability
to bind insulin receptor (IR) that regulates the downstream signaling pathway.
Insulin sequence and blood glucose level usually vary among animals due to
species specificity. The study of genetic variation of insulin, blood glucose
level and diabetics symptoms development in Aves is interesting because of its
optimal high blood glucose level than mammals. Therefore, it is of interest to
study its evolutionary relationship with other mammals using sequence data.
Hence, we compiled 32 Aves insulin from GenBank to compare its sequence-structure
features with phylogeny for evolutionary inference. The analysis shows long
conserved motifs (about 14 residues) for functional inference. These sequences
show high leucine content (20%) with high instability index (>40). Amino acid
position 11, 14, 16 and 20 are variable that may have contribution to binding to
IR. We identified functionally critical variable residues in the dataset for
possible genetic implication. Structural models of these sequences were developed
for surface analysis towards functional representation. These data find
application in the understanding of insulin function across species.
PMID- 25848167
TI - In silico pharmacokinetic and molecular docking studies of small molecules
derived from Indigofera aspalathoides Vahl targeting receptor tyrosine kinases.
AB - Angiogenesis is the formation of new blood vessels from preexisting vascular
network that plays an important role in the tumor growth, invasion and
metastasis. Anti-angiogenesis targeting tyrosine kinases such as vascular
endothelial growth factor receptor 2 (VEGFR2) and platelet derived growth factor
receptor beta (PDGFRbeta) constitutes a successful target for the treatment of
cancer. In this work, molecular docking studies of three bioflavanoid such as
indigocarpan, mucronulatol, indigocarpan diacetate and two diterpenes namely
erythroxydiol X and Y derived from Indigofera aspalathoides as PDGFRbeta and
VEGFR2 inhibitors were performed using computational tools. The crystal
structures of two target proteins were retrieved from PDB website. Among the five
compounds investigated, indigocarpan exhibited potent binding energy DeltaG =
7.04 kcal/mol with VEGFR2 and DeltaG = -4.82 with PDGFRbeta compared to
commercially available anti-angiogenic drug sorafenib (positive control). Our
results strongly suggested that indigocarpan is a potent angiogenesis inhibitor
as ascertained by its potential interaction with VEGFR2 and PDGFRbeta. This
hypothesis provides a better insight to control metastasis by blocking
angiogenesis.
PMID- 25848168
TI - High quality SNPs/Indels mining and characterization in ginger from ESTs data
base.
AB - Ginger (Zingiber officinale Rosc.) is an important herb of the family
Zingiberaceae. It is accepted as a universal cure for a multitude of diseases in
Indian systems of medicine and its rhizomes are equally popular as a spice
ingredient throughout Asia. SNPs, the definitive genetic markers, representing
the finest resolution of a DNA sequence, are abundantly found in populations
having a lower rate of mutation and are used for genomic analysis. The public
ESTs sequences mostly lack quality files, making high quality SNPs detection more
difficult since it is exclusively based on sequence comparisons. In the present
study, current dbESTs of NCBI was mined and 38115 ginger ESTs sequences were
obtained and assembled into contigs using CAP3 program. In this analysis, recent
software tool QualitySNP was used to detect 11523 potential SNPs sites, 8810 high
quality SNPs and 1008 indels polymorphisms with a frequency of 1.61 SNPs / 10
kbp. Of ESTs libraries generated from three ginger tissues together, rhizomes had
a frequency of 0.32 SNPs and 0.03 indels per 10 kbp whereas the leaves had a
frequency of 2.51 SNPs and 0.23 indels per 10 kbp and root is showing relative
frequency of 0.76/10 kbp SNPs and 0.02/10 kbp indels. The present analysis
provides additional information about the tissue wise presence of haplotypes
(222), distribution of high quality exonic (2355) and intronic (6455) SNPs and
information about singletons (7538) in addition to contigs transitions and
transversions ratio (0.57). Among all tissue detected SNPs, transversions number
is higher in comparison to the number of transitions. Quality SNPs detected in
this work can be used as markers for further ginger genetic experiments.
PMID- 25848169
TI - Application of centrality measures in the identification of critical genes in
diabetes mellitus.
AB - The connectivity of a protein and its structure is related to its functional
properties. Many experimental approaches have been employed for the
identification of Diabetes Mellitus (DM) associated candidate genes. Therefore,
it is of interest to use var ious graph centrality measures integrated with the
genes associated with the human Diabetes Mellitus network for the identification
of potential targets. We used 2728 genes known to cause Diabetes Mellitus from
Jensenlab (Novo Nordisk Foundation Center for Protein Research, Denmark) for this
analysis. A protein-protein interaction network was further constructed using a
tool Centralities in Biological Networks (CentiBiN) with 1020 nodes after
eliminating the duplicates, parallel edges, self -loop edges and unknown Human
Protein Reference Database (HPRD) IDS. We used fourteen centralities measures
which are useful in identifying the structural characteristic of individuals in
the network. The results of the centrality measures are highly correlated. Thus,
we identified genes that are critically associated with DM. We further report the
top ten genes of all fourteen centrality measures for further consideration as
targets for DM.
PMID- 25848170
TI - In vitro Osteogenic impulse effect of Dexamethasone on periodontal ligament stem
cells.
AB - Periodontium is a complex organ composed of mineralized epithelial and connective
tissue. Dexamethasone could stimulate proliferation of osteoblast and
fibroblasts. This study aimed to assess the osteogenic effect of dexamethasone on
periodental ligament (PDL) stem cells. PDL stem cells were collected from
periodontal ligament tissue of root of extracted premolar of young and healthy
people. The stem cells were cultured in alpha-MEM Medium in three groups, one
group with basic medium contains (alpha- MEM and FBS 10 % and 50 mmol of beta_
gelisrophosphat and L_ ascorbic acid ug/ml), the second group: basic medium with
dexamethasone and the third one: basic medium without any osteogenic stimulant.
Mineralization of cellular layer was analyzed with Alizarin red stain method.
Osteogenic analysis was done by Alkaline phosphates and calcium test. These
analysis indicated that the amount of intra-cellular calcium and alkaline
phosphates in the Dexamethasone group was far more than the control and basic
group (P<0.05). The results of Alizarin red stain indicated more mineralization
of cultured cells in Dexamethasone group (P<0.05). The study results showed that
Dexamethasone has significant osteogenic effect on PDL stem cells and further
studies are recommended to evaluate its effect on treatment of bone disorders.
PMID- 25848171
TI - A study on the regulatory network with promoter analysis for Arabidopsis DREB
genes.
AB - Dehydration response element binding factors (DREBs) are one of the principal
plant transcription factor subfamilies that regulate the expression of many
abiotic stress-inducible genes. This sub-family belongs to AP2 transcription
factor family and plays a considerable role in improving abiotic stresses
tolerance in plants. Therefore, it is of interest to identify critical cis-acting
elements involved in abiotic stress responses. In this study, we survey promoter
cis-elements for ATDREBs genes (Arabidopsis thaliana DREBs). Regulatory networks
based on ATDREB candidate genes were also generated to find other genes that are
functionally similar to DREBs. The study was conducted on all 20 Arabidopsis
thaliana non redundant DREB genes stored in RefSeq database. Promoter analysis
and regulatory network prediction was accomplished by use of Plant CARE program
and GeneMANIA web tool, respectively. The results indicated that among all genes,
DREB1A, DREB1C, DREB2C, DREB2G and DEAR3 have the most type of diverse motifs
involved in abiotic stress responses. It is implied that co-operation of abscisic
acid, ethylene, salicylic acid and methyl jasmonate signaling is crucial for the
regulation of the expression of drought and cold responses through DREB
transcription factors. Gene network analysis showed different co-expressed but
functionally similar genes that had physical and functional interactions with
candidate DREB genes.
PMID- 25848172
TI - ISOB: A Database of Indigenous Snake Species of Bangladesh with respective known
venom composition.
AB - At present there is no well structured database available for the venomous snakes
and venom composition of snakes in the world although venom has immense
importance in biomedical research. Searching for a specific venom component from
NCBI, PDB or public databases is troublesome, because they contain huge amount of
data entries. Therefore, we created a database named "ISOB" which is a web
accessible unique secondary database that represents the first online available
bioinformatics resource showing venom composition of snakes. This database
provides a comprehensive overview of seventy-eight indigenous snake species
covering description of snakes supplemented with structural information of the
relevant individual available venom proteins. We strongly believe that this
database will contribute significantly in the field of bioinformatics,
environmental research, proteomics, drug development and rationale drug
designing. AVAILABILITY: The database is freely available at
http://www.snakebd.com/.
PMID- 25848173
TI - Lung resection using transumbilical incision: an animal survival study.
AB - INTRODUCTION: Transumbilical single-port surgery is a potentially less invasive
approach to many types of abdominal surgeries and offers better cosmetic outcomes
than conventional 3-port laparoscopic surgery. It avoids the complication of
intercostal neuralgia and may reduce the risk of pulmonary complications after
video-assisted thoracic surgery. This study evaluated the feasibility of
transumbilical lung wedge resection. METHODS: Lung resection was performed in 11
beagle dogs weighing 5.9 to 8.5 kg. A 3-cm umbilical incision and one
diaphragmatic incision were made, and an endoscopic stapler was used. The
diaphragmatic incisions were repaired under video guidance using a V-Loc knotless
suturing device (Covidien, Mansfield, Massachusetts). Animals were monitored
daily for signs of postoperative infection. White blood cell count, C-reactive
protein level, and IL-6 level were measured in all animals. Animals were
euthanized 14 days after surgery and underwent necropsy evaluation. RESULTS:
Accurate lung resection was achieved in 10 of 11 animals during a median
operative time of 98 minutes (range 60-165). In 1 animal, transumbilical lung
resection was not possible and was converted to thoracotomy. All animals survived
without major postoperative complications. At necropsy, evidence of uneventful
healing of the stapled resection margin and diaphragmatic wound were found. There
was no evidence of vital organ injury or intrathoracic infection. CONCLUSION: A
transumbilical approach to thoracic cavity exploration and stapled lung resection
is technically feasible. Primary suturing of the diaphragmatic incision is a
simple and effective means of diaphragmatic wound closure. This may be an
alternative to video-assisted thoracic surgery for the management of simple
thoracic disease.
PMID- 25848174
TI - Laparoscopic adjustable gastric band: 4-year experience and learning curve.
AB - BACKGROUND AND OBJECTIVES: Laparoscopic adjustable gastric banding has become the
most popular procedure for the treatment of morbid obesity in Europe. The
objectives of this series are to report the results of the 4-year experience of a
single surgeon and to define the learning curve. METHODS: A retrospective review
of 156 patients who underwent laparoscopic adjustable gastric banding between
October 2006 and May 2010 was performed. Patients were separated into 3 groups:
group 1 comprised the first 50 patients; group 2 comprised the second 50
patients; and group 3 comprised the last group of patients, with a total of 56
patients. RESULTS: The male-to-female ratio was 1:4 (33 male and 133 female
patients). The mean age was 38 years (range, 17-62 years). The mean preoperative
body mass index was 44.9 kg/m(2). The mean percent excess weight loss was 41.7%
at the 1-year follow-up visit (153 patients, 98%), 49.7% at the 2-year follow-up
visit (147 patients, 94%), and 50.2% at the 3-year follow-up visit (127 patients,
81%). The overall complication rate and major complication rate were 15.4% and
3.2%, respectively. There were no deaths. Percent excess weight loss, length of
hospitalization (in days), and complication rates were compared among the 3
groups. No significant differences were noted among the groups except in the
number of complications (P < .001), but all data were clearly improved in groups
2 and 3. CONCLUSIONS: The analyses in this study have documented one more time
that laparoscopic adjustable gastric banding is an effective procedure for the
treatment of morbid obesity, achieving >50% excess weight loss at 3 years. It is
a procedure with certain complications even when performed by a surgeon with
previous experience in laparoscopic surgery. According to our subset analysis,
the learning curve is at least 50 procedures.
PMID- 25848175
TI - Late results after splenectomy in adult idiopathic thrombocytopenic purpura.
AB - BACKGROUND: We performed a retrospective study on patients with idiopathic
thrombocytopenic purpura (ITP) to evaluate the response to splenectomy in
relation to preoperative platelet count. MATERIALS AND METHODS: Two groups of
patients operated on with laparoscopic or open splenectomy for ITP, with a
platelet count <=30,000/MUL (study group: 22 patients) and >30,000/MUL (control
group: 18 patients), respectively, were compared. The two groups were homogeneous
in relation to age, sex, length of preoperative steroid therapy, and time
interval between diagnosis and surgery (Student t test with P > .1). The results
of surgery were evaluated at one year after splenectomy. Positive response to
surgery, according to the American Society of Hematologic Guidelines, was
considered in patients with a postoperative platelet count >=100,000/MUL or in
patients with a postoperative platelet count >=30,000/MUL and a twofold increase
in platelet count from baseline, in the absence of bleeding. The postoperative
platelet count increase rate was statistically related to preoperative platelet
count in both the study and control groups. Statistical analysis was performed
using the Student's t test for independent sample and the Pearson correlation in
a 2-tailed test. RESULTS: No relationship between preoperative platelet count and
postoperative platelet percent increase was observed in the control group (r =
0.41; P = .089), whereas a significant negative correlation (r = -0.68; P =
.0004) was found in the study group. CONCLUSIONS: A higher increase of
postoperative percent platelet count may be predicted in patients with a low
preoperative platelet count.
PMID- 25848176
TI - Small bowel obstruction after laparoscopic gastric bypass with nonclosure of
mesenteric defects.
AB - BACKGROUND AND OBJECTIVES: There is a wide variation of reported incidence of
small bowel obstruction (SBO) after laparoscopic Roux-en-Y gastric bypass (LGB).
There is also wide variation in technique, not only in placement of the Roux
limb, but also regarding closure or nonclosure of the mesenteric defects. The
objective of this study was to examine the incidence and characteristics of SBO
after antecolic antegastric bypass with nonclosure of the mesenteric defect of
the jejunojejunal anastomosis. METHODS: This is a retrospective review of a
series of consecutive LGBs over a 3-year period. All procedures were performed by
the same surgeon using the same technique. In no case was the mesenteric defect
closed. A prospectively maintained database was used for data collection.
Patients who returned with an SBO were the study group, and those who underwent
revisional bariatric surgery or conversion to open operation were excluded.
RESULTS: There were 249 primary LGBs performed during the study period; 15 of the
operations were followed by SBO, for an incidence of 6.0%. Four cases were caused
by an internal hernia (IH), for an incidence of 1.6%, and 11 were caused by
adhesions, which accounted for 73% of the SBOs. CONCLUSIONS: SBO after LGB is a
relatively common complication. The incidence of SBO from IH with nonclosure of
the mesenteric defect is similar to that in other series where the defect is
closed. Regardless of the cause of the SBO, operative treatment of the patient
who has a gastric bypass remains the definitive standard and should not be
delayed.
PMID- 25848177
TI - Early postoperative pain after keyless abdominal rope-lifting surgery.
AB - BACKGROUND AND OBJECTIVES: Keyless abdominal rope-lifting surgery is a novel,
gasless, single-incision laparoscopic surgical technique. In this study we aimed
to compare the postoperative pain from keyless abdominal rope-lifting surgery
with carbon dioxide laparoscopy performed for benign ovarian cysts. METHODS:
During a 20-month period, 77 women underwent surgery for a benign ovarian cyst.
Keyless abdominal rope-lifting surgery and conventional carbon dioxide
laparoscopy techniques were used for the operations in 32 women and 45 women,
respectively. The 2 operative techniques were compared with regard to demographic
characteristics; preoperative, intraoperative, and postoperative data including
early postoperative pain scores; and frequency of shoulder pain and analgesic
requirements. RESULTS: Data regarding demographic characteristics, preoperative
findings, cyst diameters and rupture rates, intra-abdominal adhesions,
intraoperative blood loss, and postoperative hospital stay did not differ between
groups (P > .05). However, the mean operative and abdominal access times were
significantly longer in the keyless abdominal rope-lifting surgery group (P <
.05). Visual analog scale pain scores at initially and at the second, fourth, and
24th hours of the postoperative period were significantly lower in the keyless
abdominal rope-lifting surgery group (P < .05). Similarly, keyless abdominal rope
lifting surgery caused significantly less shoulder pain and additional analgesic
use (P < .05). CONCLUSION: Keyless abdominal rope-lifting surgery seems to cause
less pain in the management of benign ovarian cysts in comparison with
conventional carbon dioxide laparoscopy.
PMID- 25848178
TI - Telephone follow-up by a midlevel provider after laparoscopic inguinal hernia
repair instead of face-to-face clinic visit.
AB - BACKGROUND AND OBJECTIVES: The need for more cost- and time-efficient provision
of medical care has prompted an interest in remote or telehealth approaches to
delivery of health care. We present a study examining the feasibility and
outcomes of implementation of a telephone follow-up program for laparoscopic
inguinal hernia repair. METHODS: This is a retrospective review of consecutive
patients who prospectively agreed to undergo telephone follow-up after
laparoscopic inguinal hernia repair instead of standard face-to-face clinic
visits. Patients received a telephone call from a dedicated physician assistant 2
to 3 weeks after surgery and answered a predetermined questionnaire. A face-to
face clinic visit was scheduled based on the results of the call or on patient
request. RESULTS: Of 62 patients who underwent surgery, all agreed to telephone
follow-up instead of face-to-face clinic visits. Their mean round-trip distance
to the hospital was 122 miles. Fifty-five patients (88.7%) successfully completed
planned telephone follow-up. Three patients (4.8%) were lost to follow-up, and 4
(6.5%) were erroneously scheduled for a clinic appointment. Of the 55 patients
who were reached by telephone, 50 (90.9%) were satisfied and declined an in
person clinic visit. Five patients (9.1%) returned for a clinic appointment based
on concerns raised during the telephone call. Of these, 1 was found to have an
early hernia recurrence and 1 had a seroma. CONCLUSION: Telephone follow-up by a
midlevel provider after laparoscopic inguinal hernia repair is feasible and
effective and is well received by patients.
PMID- 25848179
TI - Transient occlusion of uterine arteries in laparoscopic uterine surgery.
AB - BACKGROUND AND OBJECTIVES: This study was conducted to determine the feasibility
and effectiveness of transient occlusion of the uterine arteries (TOUA) during
laparoscopic surgery for benign uterine tumors, with preservation of fertility.
METHODS: Patients with uterine myoma or adenomyoma underwent laparoscopic uterine
surgery, with or without TOUA, performed by a single surgeon (Y.-S.K.). Surgical
outcomes included operative time; occurrence of intraoperative injury of blood
vessels, nerves, and pelvic organs; and intraoperative blood loss. RESULTS: Of
the 168 surgical patients included in this study, 144 were enrolled consecutively
during the study period, and 24 had undergone adenomectomy before the study
period. A total of 104 women (70 with myoma; 34 with adenomyoma) seeking uterine
preservation underwent laparoscopic surgery with TOUA for benign uterine tumors.
Sixty-four women (40 with myoma; 24 with adenomyoma) underwent surgery without
TOUA. The mean total surgical time of the TOUA groups was 74.85 minutes for
uterine myoma and 84.09 minutes for uterine adenomyoma. The mean estimated blood
loss during laparoscopic myomectomy and adenomyomectomy was less in the TOUA
groups than in the non-TOUA groups (109 vs. 203.4 mL in myomectomy, P < .05;
148.1 vs. 158.9 mL in adenomyomectomy; P < .05). Time to perform TOUA was 13.9
minutes in laparoscopic myomectomy and 7.33 minutes in laparoscopic
adenomyomectomy. The hospital stay of the TOUA groups was 3.32 days for uterine
myoma and 3.82 days for uterine adenomyoma. No intraoperative conversion to
laparotomy was necessary, and no major complications occurred during any of the
procedures. CONCLUSION: Laparoscopic uterine surgery with TOUA could be a safe
and effective surgical method for women with symptomatic benign uterine tumors
who wish to preserve fertility.
PMID- 25848180
TI - Tube cholecystostomy before cholecystectomy for the treatment of acute
cholecystitis.
AB - BACKGROUND AND OBJECTIVES: Percutaneous cholecystostomy is currently indicated
for patients with cholecystitis who might be poor candidates for operative
cholecystectomy. We performed a study to evaluate the long-term outcome of
patients undergoing emergent tube cholecystostomy. METHODS: This study was a
retrospective chart review of patients who underwent tube cholecystostomy from
July 1, 2005, to July 1, 2012. RESULTS: During the study period, 82 patients
underwent 125 cholecystostomy tube placements. Four patients (5%) died during the
year after tube placement. The mean hospital length of stay for survivors was 8.8
days (range, 1-59 days). Twenty-eight patients (34%) required at least 1
additional percutaneous procedure (range, 1-6) for gallbladder drainage. Twenty
nine patients (34%) ultimately underwent cholecystectomy. Surgery was performed a
mean of 7 weeks after cholecystostomy tube placement. Laparoscopic
cholecystectomy was attempted in 25 operative patients but required conversion to
an open approach in 8 cases (32%). In another 4 cases, planned open
cholecystectomy was performed. Major postoperative complications were limited to
2 patients with postoperative common bile duct obstruction requiring endoscopic
retrograde cholangiopancreatography, 1 patient requiring a return to the
operating room for hemoperitoneum, and 2 patients with bile leak from the cystic
duct stump. CONCLUSIONS: In high-risk patients receiving cholecystostomy tubes
for acute cholecystitis, only about one third will undergo surgical
cholecystectomy. Laparoscopic cholecystectomy performed in this circumstance has
a higher rate of conversion to open surgery and higher hepatobiliary morbidity
rate.
PMID- 25848181
TI - Laparoscopic-assisted subtotal colectomy combined with modified Duhamel procedure
for mixed constipation.
AB - BACKGROUND AND OBJECTIVES: To evaluate the effects of subtotal colectomy combined
with the modified Duhamel procedure on mixed constipation. METHODS: A total of 16
female patients with mixed constipation were enrolled and underwent subtotal
colectomy combined with the modified Duhamel procedure under laparoscopy from
April 2010 to April 2012. Before surgery, physical examinations such as the
gastrointestinal transit test, barium enema, and defecography were performed for
all the patients. After surgical treatment, 2-year follow-up was performed using
questionnaires to assess the effect of treatment. RESULTS: All 16 cases were
treated successfully, with a mean operation time of 230 minutes (range, 180-290
minutes). No intraoperative or postoperative complications were found, and no
deaths occurred. Constipation and relevant symptoms were relieved, and all
patients were satisfied with their quality of life. The gastrointestinal quality
of-life score was significantly increased 6 months postoperatively (mean, 102)
compared with preoperatively (mean, 75). CONCLUSION: Subtotal colectomy combined
with the modified Duhamel procedure under laparoscopy is effective and safe for
the treatment of mixed constipation.
PMID- 25848182
TI - Single-port robotic-assisted adrenalectomy: feasibility, safety, and cost
effectiveness.
AB - BACKGROUND AND OBJECTIVES: The introduction of robotic surgery offers patients
and surgeons new options for adrenalectomy. Whereas multiport adrenalectomies
have been safely performed using the robot, we describe our experience with the
novel technique of single-port robotic-assisted adrenalectomy. METHODS: We
performed a matched-cohort study comparing 16 single-port robotic-assisted
adrenalectomies with 16 patients from a pool of 148 laparoscopic adrenalectomies,
matched for age, gender, operative side, pathology, and body mass index. All were
operated on by 1 surgeon. RESULTS: The pathology included aldosteronoma in 44% of
patients, adrenocorticotropic hormone-dependent Cushing syndrome (bilateral
adrenalectomy) in 19%, pheochromocytoma in 13%, and other pathology in 24%. The
operative time was 183 +/- 33 minutes for single-port robotic-assisted
adrenalectomy and 173 +/- 40 minutes for laparoscopic adrenalectomy (P = .58).
The total time in the operating room was 246 +/- 33 minutes for single-port
robotic-assisted adrenalectomy and 240 +/- 39 minutes for laparoscopic
adrenalectomy (P = .57). There was 1 conversion to open adrenalectomy (6%) in
each group, both because of bleeding on the right side during bilateral
adrenalectomy. Two right-sided single-port robotic-assisted adrenalectomy
patients required conversion to laparoscopic adrenalectomy, one because of poor
visualization. There were no deaths. Complications occurred in 2 patients in each
group (intensive care unit admission, prolonged ileus). Both groups had similar
pain scores (mean of 3.7 on a scale from 1 to 10) on postoperative day 1, and
patients in the single-port robotic-assisted adrenalectomy group used less
narcotic pain medication in the first 24 hours after surgery (43 mg vs 84 mg in
laparoscopic adrenalectomy group, P < .001). The differences between the single
port robotic-assisted adrenalectomy group and laparoscopic adrenalectomy group in
length of stay (2.3 +/- 0.5 days vs 3.1 +/- 0.9 days, P = .23), percentage of
patients discharged on postoperative day 1 (56% vs 31%, P = .10), and hospital
cost (16% lower in single-port robotic-assisted adrenalectomy group, P = .17) did
not reach statistical significance. CONCLUSION: Single-port robotic adrenalectomy
is feasible; patients require less narcotic pain medication whereas costs appear
equivalent compared with laparoscopic adrenalectomy.
PMID- 25848183
TI - Laparoscopic radical trachelectomy: technique, feasibility, and outcomes.
AB - BACKGROUND AND OBJECTIVES: Our objectives are to describe our surgical technique
for laparoscopic radical trachelectomy, to evaluate its feasibility, and to
present the perioperative results at Hospital Italiano de Buenos Aires,
Argentina. METHODS: We analyzed 4 patients who underwent laparoscopic radical
trachelectomy for early-stage cervical cancer between December 2011 and May 2013.
RESULTS: Four patients were included in this study. Total laparoscopic radical
trachelectomy was performed in all cases. The mean age was 26 years (range, 19-32
years), the mean body mass index was 21 (range, 18-23), and the mean length of
hospital stay was 33 hours (range, 24-36 hours). The mean operative time was 225
minutes (range, 210-240 minutes), and no complications were reported. During the
postoperative period, only 1 patient presented with left vulvar edema, which
resolved spontaneously. The pelvic and parametrial lymph nodes, as well as the
vaginal cuff and cervical resection margins, were negative for malignancy in all
cases. On average, 18 pelvic lymph nodes (range, 15-20) were removed. The tumor
stage was IB in all 4 patients, and the mean tumor size was 17 mm (range, 12-31
mm). No patient required conversion to laparotomy. CONCLUSION: We consider
laparoscopic radical trachelectomy, performed by trained surgeons, a feasible and
safe therapeutic option as a fertility-sparing surgical technique, with good
perioperative outcomes for women with early-stage cervical cancer with a desire
to preserve their fertility. Minimally invasive surgery provides the widely known
benefits of this type of approach.
PMID- 25848184
TI - Management of renal cysts.
AB - BACKGROUND AND OBJECTIVES: Renal cysts have a high prevalence in the general
population, and their estimated incidence increases with age. Renal cyst
aspiration (usually with sclerotherapy) or open/laparoscopic decortication is a
generally effective and safe method in the treatment of symptomatic simple renal
cysts. The success rates of laparoscopic decortication and percutaneous
aspiration-sclerotherapy were compared to assist in the decision making for the
procedure. METHODS: A total of 184 patients with symptomatic simple renal cysts
were treated with either laparoscopic decortication in 149 cases or percutaneous
aspiration-sclerotherapy in 35 cases. The follow-up period was approximately 35
months, and the symptomatic and radiologic success rates of the 2 techniques were
compared retrospectively. RESULTS: Laparoscopic decortication was found to have
high success rates, a low recurrence rate, and minimal morbidity. Percutaneous
aspiration-sclerotherapy is an outpatient procedure with a minimally higher
recurrence rate. CONCLUSION: When a symptomatic cyst is encountered and treatment
of the cyst is indicated, laparoscopic decortication is a more efficient method
that offers better results than percutaneous aspiration-sclerotherapy.
PMID- 25848185
TI - The umbilical Benz incision for reduced port surgery in pediatric patients.
AB - BACKGROUND AND OBJECTIVES: For reduced port surgery in pediatric patients, the
initial umbilical incision plays an important role in both functional ability and
cosmetic impact. Larger umbilical incisions enable better manipulation of
forceps, extraction of larger surgical specimens, and easier exteriorization of
the intestine for anastomosis. We have pursued an incision of the small pediatric
umbilicus that allows for enlargement of the orifice of the abdominal opening
with preservation of the natural umbilical profile. This article aims to present
a new umbilical incision technique and describe the outcomes. METHODS: We devised
a new umbilical incision technique for reduced port surgery in pediatric
patients. Our incision is made in an inverted Y shape (Benz incision), allowing
for access port device insertion. The Benz incision technique was applied between
November 2010 and May 2014 and was retrospectively studied. RESULTS: Seventy-five
patients underwent Benz incisions. The median age of all patients was 6 years 6
months (range, 26 days to 18 years), and the median body weight was 21.7 kg
(range, 3.1-54.3 kg). Benz incisions were applied for various procedures,
including reduced port surgery with hepaticojejunostomy for congenital biliary
dilatation, portojejunostomy for biliary atresia, Meckel diverticulectomy, tumor
resection, varicocelectomy, cholecystectomy, splenectomy, ileus surgery,
ileocecal resection, and total colectomy. All patients were successfully treated,
without a significant increase in operating time or severe complications. The
cosmetic profile of the umbilicus was maintained after surgery. CONCLUSION: The
Benz incision is a feasible, effective, and scarless approach for reduced port
surgery in pediatric patients whose umbilical rings are too small for the
conventional approach.
PMID- 25848186
TI - Single-port onlay mesh repair of recurrent inguinal hernias after failed anterior
and laparoscopic repairs.
AB - BACKGROUND AND OBJECTIVES: Despite the exponential increase in the use of
laparoscopic inguinal herniorrhaphy, overall recurrence rates have remained
unchanged. Therefore, a growing number of patients are presenting with recurrent
hernias after conventional anterior and laparoscopic repairs have failed. This
study reports our experience with single-incision laparoscopic (SIL)
intraperitoneal onlay mesh (IPOM) repair of these hernias. METHODS: Patients
referred with two or more recurrences of inguinal hernia underwent SIL-IPOM from
November 1, 2009, to June 24, 2014. A 2.5-cm infraumbilical incision was made,
and an SIL port was placed intraperitoneally. Modified dissection techniques were
used: chopstick and inline dissection, 5.5-mm/52-cm/30 degrees angled
laparoscope, and conventional straight dissecting instruments. The peritoneum was
incised above the pubic symphysis, and dissection was continued laterally and
proximally, raising the inferior flap below the previous extraperitoneal mesh
while reducing any direct, indirect, femoral, or cord lipoma before placement of
antiadhesive mesh, which was fixed to the pubic ramus, as well as superiorly,
with nonabsorbable tacks before the inferior border was fixed with fibrin
sealant. The inferior peritoneal flap was then tacked back onto the mesh.
RESULTS: Nine male patients underwent SIL-IPOM. Their mean age was 53 years and
mean body mass index was 26.8 kg/m(2). Mean mesh size was 275 cm(2). Mean
operation time was 125 minutes, with a hospital stay of 1 day. The umbilical scar
length was 23 mm at the 6-week follow-up. There were no intra-/postoperative
complications, port-site hernias, chronic groin pain, or recurrence of the hernia
during a mean follow-up of 24 months. CONCLUSION: Inguinal hernias recurring
after two or more failed conventional anterior and laparoscopic repairs can be
safely and efficiently treated with SIL-IPOM.
PMID- 25848187
TI - Open versus robotic radical cystectomy with intracorporeal Studer diversion.
AB - BACKGROUND AND OBJECTIVES: To compare open versus totally intracorporeal robotic
assisted radical cystectomy, bilateral extended pelvic lymph node dissection, and
Studer urinary diversion in bladder cancer patients. METHODS: A retrospective
comparison of open (n = 42) versus totally intracorporeal (n = 32) robotic
assisted radical cystectomy, bilateral extended pelvic lymph node dissection, and
Studer urinary diversion was performed concerning patient demographic data,
operative and postoperative parameters, pathologic parameters, complications, and
functional outcomes. RESULTS: Patient demographic data and the percentages of
patients with pT2 disease or lower and pT3-pT4 disease were similar between
groups (P > .05). Positive surgical margin rates were similar between the open (n
= 1, 2.4%) and robotic (n = 2, 6.3%) groups (P > .05). Minor and major
complication rates were similar between groups (P > .05). Mean estimated blood
loss was significantly lower in the robotic group (412.5 +/- 208.3 mL vs 1314.3
+/- 987.1 mL, P < .001). Significantly higher percentages of patients were
detected in the robotic group regarding bilateral neurovascular bundle-sparing
surgery (93.7% vs 64.3%, P = .004) and bilateral extended pelvic lymph node
dissection (100% vs 71.4%, P = .001). The mean lymph node yield was significantly
higher in the robotic group (25.4 +/- 9.7 vs 17.2 +/- 13.5, P = .005). The number
of postoperative readmissions for minor complications was significantly lower in
the robotic group (0 vs 7, P = .017). Better trends were detected in the robotic
group concerning daytime continence with no pad use (84.6% vs 75%, P > .05) and
severe daytime incontinence (8.3% vs 16.6%, P > .05). No significant differences
were detected regarding postoperative mean International Index of Erectile
Function scores between groups (P > .05). CONCLUSIONS: Robotic surgery has the
advantages of decreased blood loss, better preservation of neurovascular bundles,
an increased lymph node yield, a decreased rate of hospital readmissions for
minor complications, and a better trend for improved daytime continence when
compared with the open approach.
PMID- 25848188
TI - Procedural changes to decrease complications in laparoscopic gastric bypass.
AB - BACKGROUND AND OBJECTIVES: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a
complex procedure performed in a patient population with significant medical
comorbidities. Evaluation and modification of surgical techniques can minimize
the complications associated with the lengthy learning curve for this procedure.
The purpose of this study was to evaluate a single surgeon's decade-long
experience with LRYGB, to determine whether complications decreased with
experience and surgical modifications improved perioperative outcomes. METHODS: A
retrospective review of all procedures performed by a fellowship-trained surgeon
(MK) from December 1, 2000, to October 31, 2013, identified patients who
underwent LRYGB. We evaluated perioperative outcomes in 1117 patients and
examined the impact of modification of surgical techniques on complications. The
patients were divided into 4 groups: cases 1-100 (group 1), cases 101-400 (group
2), cases 401-700 (group 3), and cases 701-1117 (group 4). RESULTS: Operating
time decreased significantly after the initial 100 cases, from 179.1 minutes for
group 1 to 122.1 minutes for group 4. With experience, early complication rates
improved from 25.0% to 5.0%, but the rates of early reoperation increased from
1.0% to 2.2% over the 4 case groups. Late complication and reoperation rates
increased from 4.0% to 10.5%. However, rates of bleeding, early stricture,
internal hernia, and wound infection all decreased after the modification of
surgical techniques. CONCLUSIONS: Operating time and early complication rates
decreased with operative experience, but late complication and early and late
reoperation rates increased. However, after modifications of surgical technique,
common complications of LRYGB decreased to rates lower than those reported in
several gastric bypass case series in the literature. The findings in this study
will be helpful to fellow bariatric surgeons who are refining their strategies
for reducing morbidity related to LRGYB.
PMID- 25848189
TI - Minimally invasive specialists and rates of laparoscopic hysterectomy.
AB - BACKGROUND AND OBJECTIVE: Despite the prevalence of hysterectomy for treatment of
benign gynecologic conditions, providers nationwide have been slow to adopt
minimally-invasive surgical techniques. Our objective is to investigate the
impact of a department for minimally invasive gynecologic surgery (MIGS) on the
rate of laparoscopic hysterectomy at an academic community hospital without
robotic technology. METHODS: This retrospective observational study included all
patients who underwent hysterectomy for benign indications from January 1, 2004,
through December 31, 2012. The primary outcome was route of hysterectomy: open,
laparoscopic, or vaginal. Secondary outcomes of interest included length of stay
and factors associated with an open procedure. RESULTS: In 2004, only 24 (8%) of
the 292 hysterectomies performed for benign conditions at Newton-Wellesley
Hospital (NWH) were laparoscopic. The rate increased to more than 50% (189/365)
by 2008, and, in 2012, 72% (316/439) of hysterectomies were performed via a
traditional laparoscopic approach. By 2012, more than 93% (411/439) of all
hysterectomies were performed in a minimally invasive manner (including total
laparoscopic hysterectomy [TLH], laparoscopic supracervical hysterectomy [LSH],
total vaginal hysterectomy [TVH], and laparoscopy-assisted vaginal hysterectomy
[LAVH]). More than 85% of the hysterectomies at NWH in 2012 were outpatient
procedures. By this time, the surgeon's preference or lack of expertise was
rarely cited as a factor leading to open hysterectomy. CONCLUSIONS: A large
diverse gynecologic surgery department transformed surgical practice from
primarily open hysterectomy to a majority (>72%) performed via the traditional
laparoscopic route and a large majority (>93%) performed in a minimally invasive
manner in less than 8 years, without the use of robotic technology. This paradigm
shift was fueled by patient demand and by MIGS department surgical mentorship for
generalist obstetrician/gynecologists.
PMID- 25848190
TI - Competence acquisition for single-incision laparoscopic cholecystectomy.
AB - BACKGROUND AND OBJECTIVES: Within the past few years, there has been a push for
an even more minimally invasive approach to biliary disease with the adoption of
single-incision laparoscopic cholecystectomy. We sought to compare 4 individual
surgeon experiences to define whether there exists a learning curve for
performing single-incision laparoscopic cholecystectomy. METHODS: We performed a
retrospective review 290 single-incision laparoscopic cholecystectomies performed
by a group of general surgeons, with varying levels of experience and training,
at 3 institutions between May 2008 and September 2010. The procedure times were
recorded for each single-incision laparoscopic cholecystectomy, ordered
chronologically for each surgeon, and subsequently plotted on a graph. The
patients were also combined into cohorts of 5 and 10 cases to further evaluate
for signs of improvement in operative efficiency. RESULTS: Of the 4 surgeons
involved in the study, only 1 (surgeon 4, laparoscopic fellowship trained with <5
years' experience) confirmed the presence of a learning curve, reaching
proficiency within the first 15 cases performed. The other surgeons had more
variable procedure times, which did not show a distinct trend. When we evaluated
the cases by cohorts of 5 cases, surgeon 4 had a significant difference between
the first and last cohort. Increased body mass index resulted in a slightly
longer operative time (P < .0063). The conversion rate to multiport laparoscopic
surgery was 3.1%. CONCLUSIONS: Our results indicate that among experienced
general surgeons, there does not seem to be a significant learning curve when
transitioning from conventional laparoscopic cholecystectomy to single-incision
laparoscopic cholecystectomy. The least experienced surgeon in the group, surgeon
4, appeared to reach proficiency after 15 cases. Greater than 5 years of
experience in laparoscopic surgery appears to provide surgeons with a sufficient
skill set to obviate the need for a single-incision laparoscopic cholecystectomy
learning curve.
PMID- 25848191
TI - The safety and efficacy of approaches to liver resection: a meta-analysis.
AB - BACKGROUND: The aim of this study is to compare the safety and efficacy of
conventional laparotomy with those of robotic and laparoscopic approaches to
hepatectomy. DATABASE: Independent reviewers conducted a systematic review of
publications in PubMed and Embase, with searches limited to comparative articles
of laparoscopic hepatectomy with either conventional or robotic liver approaches.
Outcomes included total operative time, estimated blood loss, length of
hospitalization, resection margins, postoperative complications, perioperative
mortality rates, and cost measures. Outcome comparisons were calculated using
random-effects models to pool estimates of mean net differences or of the
relative risk between group outcomes. Forty-nine articles, representing 3702
patients, comprise this analysis: 1901 (51.35%) underwent a laparoscopic
approach, 1741 (47.03%) underwent an open approach, and 60 (1.62%) underwent a
robotic approach. There was no difference in total operative times, surgical
margins, or perioperative mortality rates among groups. Across all outcome
measures, laparoscopic and robotic approaches showed no difference. As compared
with the minimally invasive groups, patients undergoing laparotomy had a greater
estimated blood loss (pooled mean net change, 152.0 mL; 95% confidence interval,
103.3-200.8 mL), a longer length of hospital stay (pooled mean difference, 2.22
days; 95% confidence interval, 1.78-2.66 days), and a higher total complication
rate (odds ratio, 0.5; 95% confidence interval, 0.42-0.57). CONCLUSION: Minimally
invasive approaches to liver resection are as safe as conventional laparotomy,
affording less estimated blood loss, shorter lengths of hospitalization, lower
perioperative complication rates, and equitable oncologic integrity and
postoperative mortality rates. There was no proven advantage of robotic
approaches compared with laparoscopic approaches.
PMID- 25848192
TI - Distal pancreatectomy and splenectomy: a robotic or LESS approach.
AB - INTRODUCTION: The role and application of robotic surgery are debated,
particularly given the expansion of laparoscopy, especially laparoendoscopic
single-site (LESS) surgery. This cohort study was undertaken to delineate
differences in outcomes between LESS and robotic distal pancreatectomy and
splenectomy. METHODS: With Institutional Review Board approval, patients
undergoing LESS or robotic distal pancreatectomy and splenectomy from September
1, 2012, through December 31, 2014, were prospectively observed, and data were
collected. The results are expressed as the median, with the mean +/- SD.
RESULTS: Thirty-four patients underwent a minimally invasive distal
pancreatectomy and splenectomy: 18 with robotic and 16 with LESS surgery. The
patients were similar in sex, age, and body mass index. Conversions to open
surgery and estimated blood loss were similar. There were two intraoperative
complications in the group that underwent the robotic approach. Time spent in the
operating room was significantly longer with the robot (297 vs 254 minutes, P =
.03), although operative duration (i.e., incision to closure) was not longer (225
vs 190 minutes; P = .15). Of the operations studied, 79% were undertaken for
neoplastic processes. Tumor size was 3.5 cm for both approaches; R0 resections
were achieved in all patients. Length of stay was similar in the two study groups
(5 vs 4 days). There was one 30-day readmission after robotic surgery.
CONCLUSIONS: Patient outcomes are similar with LESS or robotic distal
pancreatectomy and splenectomy. Robotic operations require more time in the
operating room. Both are safe and efficacious minimally invasive operations that
follow similar oncologic principles for similar tumors, and both should be in the
surgeon's armamentarium for distal pancreatectomy and splenectomy.
PMID- 25848193
TI - Laparoscopic transcystic choledochotomy with primary suture for choledocholith.
AB - BACKGROUND AND OBJECTIVES: To investigate the possibility of extracting common
bile duct (CBD) stones by laparoscopically inserting choledochoscope through the
natural orifice of the cystic duct and a mini-incision on the CBD, and the safety
of laparoscopic primary double-layer suture of the cystic duct and CBD. METHODS:
Laparoscopic transcystic choledochotomy and extraction of stones with primary
suture was performed on 194 patients with gallbladder and CBD stones from October
1, 2009, through April 30, 2012. The cystic duct was left at a diameter of 1 to
1.5 cm after removal of the gallbladder. The duct was longitudinally cut at its
ventral side to the confluence with the CBD, and the anterior wall of the CBD was
also cut longitudinally. A choledochoscope was then inserted via the enlarged
opening, and the stones were extracted from the CBD. Finally, the CBD and cystic
duct were closed by continuous mucous layer suture and seromuscular Lembert
suture, respectively. The cystic duct was ligated close to the CBD and an
abdominal drainage tube was placed. RESULTS: All surgical procedures were
successfully performed. The caliber at the confluence between the cystic duct and
the CBD was 0.3 to 0.8 cm (SD 0.4 +/- 0.1 cm), and the mini-incision of the CBD
was 0.1 to 1.1 cm (SD 0.3 +/- 0.2 cm). Abdominal drainage lasted 3 to 5 days.
Magnetic resonance cholangiopancreatography (MRCP) in 55 patients showed no
abnormal change in the CBD diameter. Two patients had bile leakage. Another
patient had intermittent abdominal pain and jaundice 5 to 7 days postoperatively,
and the retained stones spontaneously passed. The postoperative hospital stay was
6 to 13 days (SD 8 +/- 2.1 days). Observation of 176 patients (90%) lasting 1 to
30 months (SD 11 +/- 8 months) showed no recurrent stones or stricture of the
CBD. CONCLUSION: The surgical procedure of laparoscopic transcystic
choledochotomy and extraction of stones with primary suture is feasible and safe.
PMID- 25848194
TI - Sonohysterographic predictors of successful hysteroscopic myomectomies.
AB - BACKGROUND AND OBJECTIVES: The purpose of this study is to assess the rate of
persistent submucosal myomas and intrauterine scarring after hysteroscopic
myomectomy, as well as to evaluate the preoperative and intraoperative
sonohysterographic findings that will predict persistence of myomas, scarring,
and the need for repeat surgery. METHODS: Charts from all hysteroscopic
myomectomies performed by a single surgeon between 2003 and 2011 were reviewed
for preoperative, intraoperative, and postoperative sonohysterographic findings.
Predictors included myoma number, diameter and percent extension into the cavity
of the largest fibroid, and percent surgically resected. These predictors were
assessed with postoperative sonohysterography. Statistics included t test,
logistic regression, chi(2) test, and Fisher exact test. RESULTS: Among the 79
cases with postoperative sonohysterograms, 17 (21.5%) had persistent submucosal
myoma, and 9 (11.4%) had intrauterine scarring on postoperative sonohysterogram.
Repeat hysteroscopic myomectomy was required in 11 (13.9%), but none required
lysis of adhesions. The myoma number was not a significant predictor. A higher
percentage of myoma within the cavity (63.35% vs 44.89%, P < .05) and smaller
myoma size (2.22 cm vs 3.31 cm, P < .01) were significant predictors of a
complete resection, a normal postoperative sonohysterogram, and avoidance of
repeat surgery. On regression analysis, the percent of the myoma resected was the
most significant outcome predictor (P < .001). CONCLUSION: Larger myomas with a
lower percent found within the uterine cavity are less likely to be completely
resected. Percent resection at the time of surgery is the most significant
predictor of a normal postoperative sonohysterogram, as well as the best
predictor of the need for repeat surgery.
PMID- 25848195
TI - Magnetic resonance-visible meshes for laparoscopic ventral hernia repair.
AB - BACKGROUND AND OBJECTIVES: We aimed to evaluate the first human use of magnetic
resonance-visible implants for intraperitoneal onlay repair of incisional hernias
regarding magnetic resonance presentability. METHODS: Ten patients were
surgically treated with intraperitoneally positioned superparamagnetic flat
meshes. A magnetic resonance investigation with a qualified protocol was
performed on postoperative day 1 and at 3 months postoperatively to assess mesh
appearance and demarcation. The total magnetic resonance-visible mesh surface
area of each implant was calculated and compared with the original physical mesh
size to evaluate potential reduction of the functional mesh surfaces. RESULTS: We
were able to show a precise mesh demarcation, as well as accurate assessment of
the surrounding tissue, in all 10 cases. We documented a significant decrease in
the magnetic resonance-visualized total mesh surface area after release of the
pneumoperitoneum compared with the original mesh size (mean, 190 cm(2) vs 225
cm(2); mean reduction of mesh area, 35 cm(2); P < .001). At 3 months
postoperatively, a further reduction of the surface area due to significant mesh
shrinkage could be observed (mean, 182 cm(2) vs 190 cm(2); mean reduction of mesh
area, 8 cm(2); P < .001). CONCLUSION: The new method of combining magnetic
resonance imaging and meshes that provide enhanced signal capacity through direct
integration of iron particles into the polyvinylidene fluoride base material
allows for detailed mesh depiction and quantification of structural changes. In
addition to a significant early postoperative decrease in effective mesh surface
area, a further considerable reduction in size occurred within 3 months after
implantation.
PMID- 25848196
TI - A comparison of open surgery, robotic-assisted surgery and conventional
laparoscopic surgery in the treatment of morbidly obese endometrial cancer
patients.
AB - BACKGROUND AND OBJECTIVES: The intent of this retrospective study was to assess
the operative outcomes of morbidly obese endometrial cancer patients who were
treated with either open surgery (OS) or a minimally invasive procedure. METHODS:
Morbidly obese (body mass index [BMI] > 40 kg/m(2)) patients with endometrial
cancer who underwent OS, robotic-assisted laparoscopic surgery (RS), or
conventional laparoscopic surgery (LS) were eligible. We sought to discern any
outcome differences with regard to operative time, perioperative complications,
and hospital stay. RESULTS: Sixteen patients were treated with LS (BMI = 47.9
kg/m(2)), 13 were managed via RS (BMI = 51.2 kg/m(2)), and 24 underwent OS (BMI =
53.7 kg/m(2)). The OS (1.35 hours) patients had a significantly shorter operative
duration than the LS (1.82 hours) and RS (2.78 hours) patients (P < .001); blood
loss was greater in the OS (250 mL) group in comparison with the RS (100 mL) and
LS (175 mL) patients (P = .002). Moreover, the OS (4 days) subjects had a
significantly longer hospital stay than the LS (2 days) and RS (2 days) patients
(P = .002). CONCLUSION: In the present study, we ascertained that minimally
invasive surgery was associated with longer operative times but lower rates of
blood loss and shorter hospital stay duration compared with treatment comprising
an open procedure.
PMID- 25848197
TI - Histopathologic findings in the resected specimen of a sleeve gastrectomy.
AB - BACKGROUND AND OBJECTIVES: The vertical sleeve gastrectomy is quickly becoming a
preferred bariatric operation. There is a dearth of published data about
histopathologic changes in the specimens of morbidly obese patients, especially
sleeve patients. The aim of this study is to add more data about the
characteristics of the resected gastric specimens to the published literature.
METHODS: A prospective database of all patients undergoing laparoscopic sleeve
gastrectomies at a single institution was used to gather our data. Patient
characteristics such as age, sex, and initial body mass index were examined. The
pathology reports of these patients were examined for any histopathologic changes
or findings. RESULTS: One hundred forty-five patients over a 3-year period had
specimens available for review. Ninety-seven of the patients were women. The mean
starting body mass index was 47.5 kg/m(2) (range, 35-72.8 kg/m(2)). The mean age
at the time of the operation was 43.1 years. A minority of patients, 62 (49.7%),
had histopathologic findings in the resected specimens. The main histopathologic
findings were acute and chronic gastritis in 4 patients, chronic gastritis in 61,
and follicular lymphoid hyperplasia in 11. One leiomyoma and 2 fundic polyps were
found. Seventy-three patients had no histopathologic changes. CONCLUSION: A
minority of patients had pathologic findings in the resected specimens. This
study will help build a dataset regarding the resected stomachs of morbidly obese
individuals. These results can help determine what histopathologic findings can
be expected after sleeve gastrectomies.
PMID- 25848199
TI - Erratum.
PMID- 25848198
TI - Endoscopic gastrostomy button with double-lasso U-stitch in children.
AB - BACKGROUND AND OBJECTIVES: Placement of surgical gastric access is a common
operative procedure, with multiple techniques. We describe a cost-effective,
safe, and easy-to-perform primary endoscopic gastrostomy button placement in the
pediatric population, using a novel double-transcutaneous lasso U-stitch push
technique. METHODS: This is a retrospective review of a single center's
experience of 24 consecutively performed primary gastrostomy button placements in
infants and children aged 3 weeks to 20 years, from October 2012 through October
2014. RESULTS: The procedure was generally well tolerated, with no intraoperative
complications. No conversions to laparoscopic or open procedures were necessary.
There were no early tube dislodgements and no postoperative complications within
the first 4 weeks. CONCLUSION: The endoscopic primary gastrostomy button
placement with a transcutaneous lasso U-stitch is a safe, fast, elegant, and cost
effective alternative to a standard percutaneous endoscopic gastrostomy
placement.
PMID- 25848200
TI - Stenting for obstructing colon cancer: fewer complications and colostomies.
AB - BACKGROUND AND OBJECTIVES: Colonic stenting has been used in the setting of
malignant obstruction to avoid an emergent colectomy. We sought to determine
whether preoperative placement of a colonic stent decreases morbidity and the
rate of colostomy formation. METHODS: Cases of obstructing sigmoid, rectosigmoid,
and rectal cancer from January 1, 2010, to December 31, 2011, were identified in
the Nationwide Inpatient Sample (NIS) database. All patients were treated at
hospitals in the United States, and the database generated national estimates.
Postoperative complications, mortality, and the rate of colostomy formation were
analyzed. RESULTS: Of the estimated 7891 patients who presented with obstructing
sigmoid, rectosigmoid, or rectal cancer necessitating intervention, 12.1% (n =
956) underwent placement of a colonic stent, and the remainder underwent surgery
without stent placement. Of the patients who underwent stenting, 19.9% went on to
have colon resection or stoma creation during the same admission. Patients who
underwent preoperative colonic stent placement had a lower rate of total
postoperative complications (10.5% vs 21.7%; P < .01). There was no significant
difference in mortality (4.7% vs 4.2%; P = .69). The rate of colostomy formation
was more than 2-fold higher in patients who did not undergo preoperative stenting
(42.5% vs 19.5%; P < .01). Preoperative stenting was associated with increased
use of laparoscopy (32.6% vs 9.7%; P < .01). CONCLUSIONS: Our study characterizes
the national incidence of preoperative placement of a colonic stent in the
setting of malignant obstruction. Preoperative stent placement is associated with
lower postoperative complications and a lower rate of colostomy formation. The
results support the hypothesis that stenting as a bridge to surgery may benefit
patients by converting an emergent surgery into an elective one.
PMID- 25848201
TI - Text (Oral) Reading Fluency as a Construct in Reading Development: An
Investigation of its Mediating Role for Children from Grades 1 to 4.
AB - In the present study we investigated a developmentally changing role of text
reading fluency in mediating the relations of word reading fluency and listening
comprehension to reading comprehension. We addressed this question by using
longitudinal data from Grades 1 to 4, and employing structural equation models.
Results showed that the role of text reading fluency changes over time as
children's reading proficiency develops. In the beginning phase of reading
development (Grade 1), text reading fluency was not independently related to
reading comprehension over and above word reading fluency and listening
comprehension. In Grades 2 to 4, however, text reading fluency completely
mediated the relation between word reading fluency and reading comprehension
whereas it partially mediated the relation between listening comprehension and
reading comprehension. These results suggest that text reading fluency is a
dissociable construct that plays a developmentally changing role in reading
acquisition.
PMID- 25848202
TI - Optomap ultrawide field imaging identifies additional retinal abnormalities in
patients with diabetic retinopathy.
AB - PURPOSE: To compare diabetic retinopathy (DR) severity grading between Optomap
ultrawide field scanning laser ophthalmoscope (UWFSLO) 200 degrees images and an
Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard field view.
METHODS: Optomap UWFSLO images (total: 266) were retrospectively selected for
evidence of DR from a database of eye clinic attendees. The Optomap UWFSLO images
were graded for DR severity by two masked assessors. An ETDRS seven-field mask
was overlaid on the Optomap UWFSLO images, and the DR grade was assessed for the
region inside the mask. Any interassessor discrepancies were adjudicated by a
senior retinal specialist. Kappa agreement levels were used for statistical
analysis. RESULTS: Fifty images (19%) (P<0.001) were assigned a higher DR level
in the Optomap UWFSLO view compared to the ETDRS seven-field view, which resulted
in 40 images (15%) (P<0.001) receiving a higher DR severity grade. DR severity
grades in the ETDRS seven-field view compared with the Optomap UWFSLO view were
identical in 85% (226) of the images and within one severity level in 100% (266)
of the images. Agreement between the two views was substantial: unweighted kappa
was 0.74+/-0.04 (95% confidence interval: 0.67-0.81) and weighted kappa was
0.80+/-0.03 (95% confidence interval: 0.74-0.86). CONCLUSION: Compared to the
ETDRS seven-field view, a significant minority of patients are diagnosed with
more severe DR when using the Optomap UWFSLO view. The clinical significance of
additional peripheral lesions requires evaluation in future prospective studies
using large cohorts.
PMID- 25848203
TI - Current perspectives on ranibizumab.
AB - BACKGROUND: This review summarizes the Phase III studies addressing intravitreal
ranibizumab treatment in patients with neovascular age-related macular
degeneration (AMD), macular edema (ME) from retinal vein occlusion (RVO), and
diabetic ME (DME). RESULTS: The data from 12 major Phase III studies: six studies
in patients with neovascular AMD, two studies in patients with ME from RVO, and
four studies in patients with DME demonstrate significant improvement in vision
in patients undergoing treatment with intravitreal ranibizumab over patients
receiving no treatment or receiving only grid laser. These effects are achieved
with low incidences of ocular and nonocular adverse events. CONCLUSION:
Intravitreal ranibizumab is a highly effective and safe therapy for improving
vision and reducing vision loss in patients with neovascular AMD, ME from RVO,
and DME. Patients generally require long-term treatment although some data show
that frequency of treatment necessary to maintain visual outcomes decreases over
time.
PMID- 25848204
TI - Measurement of serum and vitreous concentrations of anti-type II collagen
antibody in diabetic retinopathy.
AB - BACKGROUND: Autoimmune mechanisms have been postulated as a cause of diabetic
retinopathy (DR), as several autoantibodies have reportedly been detected in the
serum of DR patients. In this present study, we measured serum and vitreous
levels of anti-type II collagen (anti-II-C) antibodies in DR patients and
investigated their association with the mechanism of development of DR. PATIENTS
AND METHODS: Blood samples were obtained from patients with proliferative DR and
from patients with diabetic macular edema who underwent vitrectomy at Osaka
Medical College, Takatsuki City, Osaka, Japan. Diabetic patients without DR were
also included. The control group consisted of age- and sex-matched patients with
noninflammatory eye diseases who underwent eye surgery for retinal detachment or
for cataracts. The levels of anti-II-C immunoglobulin (Ig)G antibody in the
vitreous and serum were measured using a human/monkey anti-II-C IgG assay kit.
RESULTS: The serum levels of anti-II-C IgG antibody were significantly higher in
the DR patients than in the patients with noninflammatory eye disease (56.8+/
33.8 units/mL versus 30.5+/-13.7 units/mL, respectively; P<0.05, Fisher's exact
test). These levels were also significantly higher in the diabetic patients
without DR than in the patients with noninflammatory eye disease (76.3+/-49.7
units/mL versus 30.5+/-13.7 units/mL, respectively; P<0.01, Fisher's exact test).
However, anti-II-C IgG antibody levels were unable to be detected in all of the
obtained vitreous fluid samples. CONCLUSION: The development and progression of
DR may be related to a mechanism involving intraocular type II collagen, which
normally has immunological tolerance as a sequestered antigen. In DR, the
disruption of the blood-retinal barrier leads to contact between the intraocular
type II collagen and immunocompetent cells, and to subsequent activation of the
autoimmune mechanism.
PMID- 25848205
TI - Vitreous estrogen levels in patients with an idiopathic macular hole.
AB - PURPOSE: Estrogen, a female hormone, activates collagenase and might be
associated with the pathogenesis of vitreoretinal collagen fiber disease. The
purpose of the present study was to investigate the vitreous levels of estrone
(E1) and estradiol (E2) in subjects with an idiopathic macular hole (IMH).
METHODS: Vitreous samples were obtained from ten female patients with an IMH and
from nine female patients with other retinal diseases (six with rhegmatogenous
retinal detachment and three with age-related macular degeneration) as a control
at the time of vitreous surgery. E1 and E2 levels in the vitreous samples were
then determined using the Coat-A-Count((r)) Estradiol Radioimmunoassay (RIA) Kit
and the DSL-70 Estrone RIA Kit, respectively. RESULTS: The mean vitreous levels
of E1 and E2 in the subjects with IMH were 1.83+/-2.00 pg/mL and 7.03+/-2.97
pg/mL, respectively, whereas in the control subjects they were 2.42+/-1.25 pg/mL
and 4.90+/-2.90 pg/mL, respectively. Thus, the vitreous E2 levels in the subjects
with IMH were significantly higher than in the controls (P<0.05). CONCLUSION: The
findings of this study suggest that E2 might be associated with the pathogenesis
of IMH, but further investigation is needed to elucidate that association.
PMID- 25848206
TI - Unilateral rhino-orbital-cerebral mucormycosis with contralateral endogenous
fungal endophthalmitis.
AB - Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon but fatal fungal
infection. We report a rare case of unilateral ROCM with ipsilateral central
retinal artery occlusion and contralateral choroiditis, which later progressed to
endogenous fungal endophthalmitis. The patient was successfully treated with
sinuses debridement, systemic liposomal amphotericin B, and intravitreal
amphotericin B. The endophthalmitis completely resolved with good vision, but the
ROCM eye remained blind due to central retinal artery occlusion.
PMID- 25848207
TI - The effect of Nd:YAG laser treatment of posterior capsule opacification on
anterior chamber depth and refraction in pseudophakic eyes.
AB - PURPOSE: This was a prospective descriptive study to determine the changes in
intraocular lens (IOL) position after neodymium-doped yttrium-aluminum-garnet
(Nd:YAG) laser posterior capsulotomy by measuring anterior chamber depth (ACD)
and refraction, including the spherical equivalent (SE) and cylinder. MATERIALS
AND METHODS: Forty-seven pseudophakic eyes with posterior capsule opacification
of 29 patients were included. Nd:YAG laser posterior capsulotomy was performed.
Patients' ACD and refraction were measured before the treatment, as well as after
the treatment at 1 week and 3 months. IOLMaster((r)) and an automated
refractometer were used at the Department of Ophthalmology, King Chulalongkorn
Memorial Hospital, Bangkok, Thailand. RESULTS: There were no statistically
significant differences in ACD and SE before and after laser treatment at 1 week
and 3 months (repeated analysis of variance, P=0.582 and P=0.269, respectively).
Both backward IOL movement (number [n]=29) and forward IOL movement (n=18) were
found. Some changes in cylindrical refraction were found at 1 week, but decreased
at 3 months after capsulotomy (baseline cylinder: -1.16; cylinder at 1 week and 3
months: -1.00 and -1.14, respectively; P=0.012). These changes were the same with
one-piece and three-piece IOLs. CONCLUSION: Nd:YAG laser posterior capsulotomy
did not significantly change ACD and SE. It led to cylinder change at 1 week
after laser, but the effect decreased at 3 months. This effect was small and may
not be clinically significant.
PMID- 25848208
TI - Glu-Trp-ONa or its acylated analogue (R-Glu-Trp-ONa) administration enhances the
wound healing in the model of chronic skin wounds in rabbits.
AB - The management of chronic skin wounds represents a major therapeutic challenge.
The synthesized dipeptide (Glu-Trp-ONa) and its acylated analogue (R-Glu-Trp-ONa)
were assessed in the model of nonhealing dermal wounds in rabbits in relation to
their healing properties in wound closure. Following wound modeling, the rabbits
received a course of intraperitoneal injections of Glu-Trp-ONa or R-Glu-Trp-ONa.
Phosphate-buffered saline and Solcoseryl(r) were applied as negative and positive
control agents, respectively. An injection of Glu-Trp-ONa and R-Glu-Trp-ONa
decreased the period of wound healing in animals in comparison to the control and
Solcoseryl-treated groups. Acylation of Glu-Trp-ONa proved to be beneficial as
related to the healing properties of the dipeptide. Subsequent zymography
analyses showed that the applied peptides decreased the proteolytic activity of
matrix metalloproteinases MMP-9, MMP-8, and MMP-2 in the early inflammatory phase
and reversely increased the activity of MMP-9, MMP-8, and MMP-1 in the remodeling
phase. Histological analyses of the wound sections (hematoxylin-eosin, Mallory's
staining) confirmed the enhanced formation of granulation tissue and re
epithelialization in the experimental groups. By administering the peptides,
wound closures increased significantly through the modulation of the MMPs'
activity, indicating their role in wound healing.
PMID- 25848209
TI - Brentuximab vedotin for relapsed or refractory Hodgkin's lymphoma.
AB - Brentuximab vedotin is a promising antibody-drug conjugate (ADC) targeting CD30
of tumor cells. It selectively delivers monomethyl auristatin E (MMAE) into CD30
expressing cells and induces tumor cell apoptosis. Various clinical trials have
provided evidence that it is effective in relapsed or refractory Hodgkin's
lymphoma (HL), and it has also shown its advantages in other CD30-positive
lymphomas. In this review, we focus on the structure, mechanisms, and
pharmacokinetics of brentuximab vedotin. We also summarize clinical trials with
brentuximab vedotin and make recommendations for brentuximab vedotin in the
treatment of relapsed or refractory HL.
PMID- 25848210
TI - Single and multiple dose pharmacokinetics and tolerability of HX-1171, a novel
antioxidant, in healthy volunteers.
AB - BACKGROUND: HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone) is a promising
antioxidant with therapeutic potential for hepatic fibrosis. The aim of this
study was to investigate the tolerability and pharmacokinetics of HX-1171 in
healthy volunteers. METHODS: A randomized, single-blind, placebo-controlled, dose
escalation study was conducted in 83 subjects. In the single ascending dose
study, 20, 40, 80, 160, 300, 600, 1,200, 1,500 or 2,000 mg of HX-1171 was
administered to 67 subjects. In the multiple ascending dose study, 500 or 1,000
mg was administered to 16 subjects for 14 days. The plasma and urine
concentrations of HX-1171 were determined by using a validated liquid
chromatography-mass spectrometry method. Pharmacokinetic parameters were obtained
by non-compartmental analysis. Tolerability was assessed based on physical
examinations, vital signs, clinical laboratory tests, and electrocardiograms.
RESULTS: Adverse events reported in the study were all mild in intensity and
resolved without any sequelae. HX-1171 was rapidly and minimally absorbed with a
median time at maximal concentration of 0.63-1.50 hours and slowly eliminated
with a terminal half-life of 21.12-40.96 hours. Accumulation index ranged from
2.0 to 2.2 after repeated dosing for 14 days. For both the single and multiple
doses administrations, urinary concentrations indicated that less than 0.01% of
the HX-1171 administered was excreted in urine. CONCLUSION: HX-1171 was well
tolerated and minimally absorbed in healthy volunteers. The pharmacokinetic
profile of HX-1171 was consistent with once-a-day dosing.
PMID- 25848211
TI - Design and prediction of new anticoagulants as a selective Factor IXa inhibitor
via three-dimensional quantitative structure-property relationships of
amidinobenzothiophene derivatives.
AB - Factor IXa (FIXa), a blood coagulation factor, is specifically inhibited at the
initiation stage of the coagulation cascade, promising an excellent approach for
developing selective and safe anticoagulants. Eighty-four amidinobenzothiophene
antithrombotic derivatives targeting FIXa were selected to establish three
dimensional quantitative structure-activity relationship (3D-QSAR) and three
dimensional quantitative structure-selectivity relationship (3D-QSSR) models
using comparative molecular field analysis and comparative similarity indices
analysis methods. Internal and external cross-validation techniques were
investigated as well as region focusing and bootstrapping. The satisfactory q (2)
values of 0.753 and 0.770, and r (2) values of 0.940 and 0.965 for 3D-QSAR and 3D
QSSR, respectively, indicated that the models are available to predict both the
inhibitory activity and selectivity on FIXa against Factor Xa, the activated
status of Factor X. This work revealed that the steric, hydrophobic, and H-bond
factors should appropriately be taken into account in future rational design,
especially the modifications at the 2'-position of the benzene and the 6-position
of the benzothiophene in the R group, providing helpful clues to design more
active and selective FIXa inhibitors for the treatment of thrombosis. On the
basis of the three-dimensional quantitative structure-property relationships, 16
new potent molecules have been designed and are predicted to be more active and
selective than Compound 33, which has the best activity as reported in the
literature.
PMID- 25848212
TI - Effect of varying doses of tamoxifen on ovarian histopathology, serum VEGF, and
endothelin 1 levels in ovarian hyperstimulation syndrome: an experimental study.
AB - OBJECTIVE: To examine the effects of low-to-high doses of tamoxifen on ovarian
histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation
syndrome (OHSS) in an experimental setting. MATERIALS AND METHODS: A total of 20
female Wistar albino rats, 22 days of age, were randomly divided into four
groups. Follicle-stimulating hormone 10 IU was administered subcutaneously in 15
rats on 4 consecutive days, with OHSS induction on day 5 by 30 IU of human
chorionic gonadotropin. Group 1 (n=5) comprised 35-day-old control rats, group 2
(n=5) 35-day-old OHSS rats, group 3 (n=5) 27-day-old OHSS rats receiving 1 mg/kg
of oral tamoxifen for 7 days, group 4 (n=5) 27-day-old OHSS rats receiving 3
mg/kg of oral tamoxifen for 7 days. All rats were decapitated on day 35. Serum
VEGF, endothelin 1, and ovarian follicular reserve were assessed in all rats.
Kruskal-Wallis variance analysis and the Mann-Whitney U-test were used for
statistical comparisons. A Bonferroni correction was performed to control the
inflation of significance, with a significance level set at a P-value of less
than 0.025. RESULTS: Despite higher serum VEGF, endothelin 1, follicular reserve,
and angiogenesis and fibrosis of the corpus luteum in the OHSS group compared to
controls, these differences were not significant (P>0.025, Mann-Whitney U-test).
There was a significant reduction in the ovarian follicular reserve in tamoxifen
groups compared to controls (P<0.025, Mann-Whitney U-test), while angiogenesis of
the corpus luteum, number of atretic follicles, fibrosis, and serum VEGF were
significantly higher in rats receiving tamoxifen (P<0.025, Mann-Whitney U-test).
Also, significantly lower follicular reserve and fibrosis were observed among
rats in the low-dose tamoxifen group in comparison with rats in the high-dose
tamoxifen group (P<0.025, Mann-Whitney U-test). No groups had a significant
change in endothelin 1 levels (P>0.025, Mann-Whitney U-test). CONCLUSION:
Tamoxifen 1 g and 3 g resulted in a dose-dependent increase in VEGF and
endothelin 1 levels, and ovarian follicle reserves were significantly reduced in
our experimental model.
PMID- 25848213
TI - Turoctocog alfa: an evidence-based review of its potential in the treatment of
hemophilia A.
AB - Turoctocog alfa is the first B-domain-truncated third generation recombinant
coagulation factor VIII (FVIII) product. Nonclinical in vitro and animal model
studies have demonstrated that turoctocog alfa has similar functional potency and
hemostatic efficacy as comparator FVIII products. With respect to discrepancies
in the level of FVIII concentrate in plasma of current FVIII products on
comparing measurement results between one-stage clot and chromogenic assays,
there was no difference in the in vitro turoctocog alfa study; however, measured
FVIII concentrate in field study was higher with the chromogenic assay (1.08
IU/mL) than with one-stage assay (0.83 IU/mL). Two published clinical studies on
previously treated patients (PTPs) and clinical pharmacokinetics have described
that the pharmacokinetic parameters are similar, and the safety and efficacy for
prevention and treatment for bleeding are also similar to those of standard half
life FVIII products. Three clinical trials are ongoing to assess the long-term
safety and efficacy of turoctocog alfa for PTPs and previously untreated
patients. Those data will be published in the near future, and it will be
possible to use turoctocog alfa for all hemophilia patients. However, studies
will be needed to confirm the turoctocog alfa profile, such as the stability of
dissolved turoctocog alfa over 24 hours at room temperature and post-marketing
clinical research aimed at meeting Europe Medicines Agency post-marketing safety
and efficacy requirements in PTPs. It is recommended to wait before using
turoctocog alfa for previously untreated patients and major surgery until further
data have been collected and published.
PMID- 25848214
TI - Lost expression of ADAMTS5 protein associates with progression and poor prognosis
of hepatocellular carcinoma.
AB - Altered expression of ADAMTS5 is associated with human carcinogenesis and tumor
progression. However, the role of ADAMTS5 in hepatocellular carcinoma (HCC) is
unclear. This study analyzed ADAMTS5 expression in HCC tissues and tested for
association with clinicopathological and survival data from HCC patients and then
explored the role of ADAMTS5 in HCC cells in vitro. Paraffin blocks from 48 HCC
patients were used to detect ADAMTS5 and vascular endothelial growth factor
(VEGF) expression and microvessel density (MVD). A normal liver cell line and HCC
cell lines were used to detect ADAMTS5 expression and for ADAMTS5 manipulation.
ADAMTS5 cDNA was stably transfected into HCC cells and ADAMTS5 expression
assessed by Western blot analysis. Tumor cell-conditioned growth medium was used
to assess human umbilical vein endothelial cell migration and Matrigel tube
formation. Xenograft assay was performed to determine the role of ADAMTS5 in
vivo. The data showed that the expression of ADAMTS5 was reduced in HCC, which
was inversely associated with VEGF expression, MVD, and tumor size and associated
with poor overall survival of HCC patients. Lentivirus-mediated ADAMTS5
expression significantly inhibited tumor angiogenesis by downregulating in vitro
expression of VEGF and inhibiting migration and tube formations, and also
inhibited tumor growth and VEGF expression and reduced MVD in vivo in a mouse
xenograft model. Taken together, these results suggest that ADAMTS5 plays a role
in suppression of HCC progression, which could be further studied as a promising
novel therapeutic target and a potential prognostic marker in HCC.
PMID- 25848215
TI - Clinical significance of DAPK promoter hypermethylation in lung cancer: a meta
analysis.
AB - Death-associated protein kinase 1 (DAPK) is an important serine/threonine kinase
involved in various cellular processes, including apoptosis, autophagy, and
inflammation. DAPK expression and activity are deregulated in a variety of
diseases including cancer. Methylation of the DAPK gene is common in many types
of cancer and can lead to loss of DAPK expression. However, the association
between DAPK promoter hypermethylation and the clinicopathological significance
of lung cancer remains unclear. In this study, we searched the MEDLINE, PubMed,
Web of Science, and Scopus databases, systematically investigated the studies of
DAPK promoter hypermethylation in lung cancer and quantified the association
between DAPK promoter hypermethylation and its clinicopathological significance
by meta-analysis. We observed that the frequency of DAPK methylation was
significantly higher in lung cancer than in non-malignant lung tissues (odds
ratio 6.02, 95% confidence interval 3.17-11.42, P<0.00001). The pooled results
also showed the presence of a prognostic impact of DAPK gene methylation in lung
cancer patients (odds ratio 3.63, 95% confidence interval 1.09-12.06, P=0.04). In
addition, we summarized these findings and discuss tumor suppressor function,
clinicopathological significance, and potential drug targeting of DAPK in lung
cancer.
PMID- 25848216
TI - Recent progress in fungus-derived bioactive agents for targeting of signaling
machinery in cancer cells.
AB - It is becoming increasingly understood that tumor cells may have different
mutations and dependencies on diverse intracellular signaling cascades for
survival or metastatic potential. Overexpression of oncogenes, inactivation of
tumor suppressor genes, genetic/epigenetic mutations, genomic instability, and
loss of apoptotic cell death are some of the mechanisms that have been widely
investigated in molecular oncology. We partition this multicomponent review into
the most recent evidence on the anticancer activity of fungal substances obtained
from in vitro and xenografted models, and these fungal substances modulate
expression of oncogenic and tumor suppressor miRNAs. There are some outstanding
questions regarding fungus-derived chemical-induced modulation of intracellular
signaling networks in different cancer cell lines and preclinical models. Certain
hints have emerged, emphasizing mechanisms via which apoptosis can be restored in
TRAIL-resistant cancer cells. Reconceptualization of the knowledge obtained from
these emerging areas of research will enable us to potentially identify natural
agents with notable anticancer activity and minimal off-target effects.
Integration of experimentally verified evidence obtained from cancer cell line
gene expression with large-scale functional screening results and pharmacological
sensitivity data will be helpful in identification of therapeutics with
substantial efficacy. New tools and technologies will further deepen our
understanding of the signaling networks that underlie the development of cancer,
metastasis, and resistance to different therapeutics at both a personal and
systems-wide level.
PMID- 25848217
TI - Novel nanoliposomal delivery system for polydatin: preparation, characterization,
and in vivo evaluation.
AB - BACKGROUND: The objective of this study was to develop a novel polydatin (PLD)
loaded liposome system using the thin film hydration technique. METHODS: The
delivery system was characterized in terms of morphology, size, zeta potential,
encapsulation efficiency, and in vitro release. In addition, a pharmacokinetic
study was carried out in rats after oral administration of PLD-loaded liposomes
in vivo. RESULTS: Transmission electron microscopy revealed that the PLD-loaded
liposomes had a homogeneous size and spherical shape. Dynamic light scattering
showed that the PLD-loaded liposomes had a smaller size with a mean value of
80.2+/-3.7 nm and a polydispersity index of 0.12+/-0.06. The encapsulation
efficiency of the prepared liposomes was 88.4%+/-3.7%. During the release
process, liposome showed two distinct phases. The first was characterized by
rapid release during the first 2 hours, which could be related to the release of
the drug adsorbed on the surface of liposomes. In the second phase, the release
rate slowed down, demonstrating a typical sustained and prolonged drug-release
behavior. The release kinetic model for the PLD-loaded liposomes fitted well with
the Weibull distribution equation. In vivo, relative oral bioavailability of the
encapsulated PLD was 282.9%, ie, significantly enhanced (P<0.05) compared with
the free drug. No histological changes occurred in the organs after
administration of PLD-loaded liposomes. CONCLUSION: PLD-loaded liposomes could
significantly prolong the drug circulation time in vivo and increase the oral
bioavailability of the drug.
PMID- 25848218
TI - Paracellular permeation-enhancing effect of AT1002 C-terminal amidation in nasal
delivery.
AB - BACKGROUND: The identification of permeation enhancers has gained interest in the
development of drug delivery systems. A six-mer peptide, H-FCIGRL-OH (AT1002), is
a tight junction modulator with promising permeation-enhancing activity. AT1002
enhances the transport of molecular weight markers or agents with low
bioavailability with no cytotoxicity. However, AT1002 is not stable in neutral pH
or after incubation under physiological conditions, which is necessary to fully
uncover its permeation-enhancing effect. Thus, we increased the stability or
mitigated the instability of AT1002 by modifying its terminal amino acids and
evaluated its subsequent biological activity. METHODS: C-terminal-amidated
(FCIGRL-NH2, Pep1) and N-terminal-acetylated (Ac-FCIGRL, Pep2) peptides were
analyzed by liquid chromatography-mass spectrometry. We further assessed
cytotoxicity on cell monolayers, as well as the permeation-enhancing activity
following nasal administration of the paracellular marker mannitol. RESULTS: Pep1
was nontoxic to cell monolayers and showed a relatively low decrease in peak area
compared to AT1002. In addition, administration of mannitol with Pep1 resulted in
significant increases in the area under the plasma concentration-time curve and
peak plasma concentration at 3.63-fold and 2.68-fold, respectively, compared to
mannitol alone. In contrast, no increase in mannitol concentration was shown with
mannitol/AT1002 or mannitol/Pep2 compared to the control. Thus, Pep1 increased
the stability or possibly reduced the instability of AT1002, which resulted in an
increased permeation-enhancing effect of AT1002. CONCLUSION: These results
suggest the potential usefulness of C-terminal-amidated AT1002 in enhancing nasal
drug delivery, which may lead to the development of a practical drug delivery
technology for drugs with low bioavailability.
PMID- 25848219
TI - Pharmacoinformatics approach for investigation of alternative potential hepatitis
C virus nonstructural protein 5B inhibitors.
AB - Hepatitis C virus (HCV) is one of the major viruses affecting the world today. It
is a highly variable virus, having a rapid reproduction and evolution rate. The
variability of genomes is due to hasty replication catalyzed by nonstructural
protein 5B (NS5B) which is also a potential target site for the development of
anti-HCV agents. Recently, the US Food and Drug Administration approved
sofosbuvir as a novel oral NS5B inhibitor for the treatment of HCV.
Unfortunately, it is much highlighted for its pricing issues. Hence, there is an
urgent need to scrutinize alternate therapies against HCV that are available at
affordable price and do not have associated side effects. Such a need is crucial
especially in underdeveloped countries. The search for various new bioactive
compounds from plants is a key part of pharmaceutical research. In the current
study, we applied a pharmacoinformatics-based approach for the identification of
active plant-derived compounds against NS5B. The results were compared to docking
results of sofosbuvir. The lead compounds with high-binding ligands were further
analyzed for pharmacokinetic and pharmacodynamic parameters based on in silico
absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile.
The results showed the potential alternative lead compounds that can be developed
into commercial drugs having high binding energy and promising ADMET properties.
PMID- 25848220
TI - Design and evaluation of effervescent floating tablets based on hydroxyethyl
cellulose and sodium alginate using pentoxifylline as a model drug.
AB - The aim of this work was to design and evaluate effervescent floating gastro
retentive drug delivery matrix tablets with sustained-release behavior using a
binary mixture of hydroxyethyl cellulose and sodium alginate. Pentoxifylline was
used as a highly water-soluble, short half-life model drug with a high density.
The floating capacity, swelling, and drug release behaviors of drug-loaded matrix
tablets were evaluated in 0.1 N HCl (pH 1.2) at 37 degrees C+/-0.5 degrees C.
Release data were analyzed by fitting the power law model of Korsmeyer-Peppas.
The effect of different formulation variables was investigated, such as wet
granulation, sodium bicarbonate gas-forming agent level, and tablet hardness
properties. Statistical analysis was applied by paired sample t-test and one-way
analysis of variance depending on the type of data to determine significant
effect of different parameters. All prepared tablets through wet granulation
showed acceptable physicochemical properties and their drug release profiles
followed non-Fickian diffusion. They could float on the surface of dissolution
medium and sustain drug release over 24 hours. Tablets prepared with 20% w/w
sodium bicarbonate at 50-54 N hardness were promising with respect to their
floating lag time, floating duration, swelling ability, and sustained drug
release profile.
PMID- 25848221
TI - Comparative efficacy of pitavastatin and simvastatin in patients with
hypercholesterolemia: a meta-analysis of randomized controlled clinical trials.
AB - BACKGROUND: Simvastatin is a statin used to lower low-density lipoprotein
cholesterol, but has limitations in patients on complicated regimens due to
concerns about drug-drug interactions. Pitavastatin is a newly developed statin
with limited drug-drug interactions. We conducted a meta-analysis to compare the
clinical efficacy of simvastatin and pitavastatin in the control of
hypercholesterolemia. METHODS: Randomized clinical trials comparing the efficacy
of pitavastatin and simvastatin were identified by searching PubMed (2000-2014)
and EMBASE (2000-2014). The primary outcome subjected to meta-analysis was
percent change in low-density lipoprotein cholesterol compared with baseline.
RESULTS: Four clinical trials were selected for meta-analysis. A total of 908
patients treated with pitavastatin (2 or 4 mg/day) and 381 patients treated with
simvastatin (20 or 40 mg/day) were included in the final statistical analysis. No
statistically significant difference was identified between treatment with
pitavastatin 4 mg/day and treatment with simvastatin 40 mg/day for 12 weeks (mean
difference -0.66; 95% confidence interval -2.92, 1.61; P=0.57). Similarly, no
statistically significant difference was observed between pitavastatin 2 mg/day
and simvastatin 20 mg/day for 4 weeks (mean difference -2.19; 95% confidence
interval -0.11, 4.49; P=0.06). Treatment with pitavastatin was noninferior to
simvastatin in all of the secondary outcomes and the safety profile was similar
between the two statins. CONCLUSION: Pitavastatin is noninferior to simvastatin
in lowering low-density lipoprotein cholesterol.
PMID- 25848222
TI - Liraglutide and obesity: a review of the data so far.
AB - The prevalence of obesity worldwide has nearly doubled since 1980 with current
estimates of 2.1 billion in 2013. Overweight and obesity lead to numerous adverse
conditions including type 2 diabetes, cardiovascular disease, stroke, and certain
cancers. The worldwide spread of obesity and associated comorbidities not only
threatens quality of life but also presents a significant economic burden. While
bariatric surgery has proven to be a viable treatment option for the morbidly
obese, there is clearly a need for less invasive alternatives. Recent research
has suggested that long-acting analogs of the gut hormone, glucagon-like peptide
1 (GLP-1), may have potential as an antiobesity treatment. The GLP-1 receptor
agonist, liraglutide (trade name Saxenda), was recently approved by the US Food
and Drug Administration as an obesity treatment option and shown in clinical
trials to be effective in reducing and sustaining body weight loss. This review
presents the basis for GLP-1-based therapies with a specific focus on animal and
human studies examining liraglutide's effects on food intake and body weight.
PMID- 25848223
TI - A perspective on the benefit-risk assessment for new and emerging pharmaceuticals
in Japan.
AB - The universal health care system in Japan is facing a historical turning point as
a result of the increasing fiscal burden, rapidly aging society, and a decreasing
population. To understand the challenges and opportunities in the Japanese
pharmaceutical market, which occupies one tenth of the global share, this review
highlights several issues related to the benefit-risk assessment that is unique
to the modern Japanese society: 1) regulatory system for new drug development; 2)
health hazards related to pharmaceuticals ("Yakugai" in Japanese); 3) drug lag;
4) problems and controversies in the vaccination policy; and 5) clinical study
misconduct. The regulatory process places a significant importance on Japanese
data collection regardless of data accumulation from other countries. Because
Yakugai has repeatedly caused tragedies and social disputes historically, the
regulatory judgments generally tend to be more prudential when safety concerns
are raised for new and emerging pharmaceuticals. Such a regulatory system has
caused more than several years of approval delays compared to delays in other
countries. The problem of drug lag still lingers on despite several regulatory
system revisions, while the solution is incompatible with the elimination of
Yakugai because the lag potentially reduces the risk of unpredictable adverse
events. The Japanese vaccination policy has also received a lot of criticism, and
needs improvements so that the decision-making process can be more transparent
and scientifically based. Additionally, repeated clinical study misconduct
damaged the reputation of Japanese clinical studies with unnecessary defrayment
in health insurance; therefore, the medical community must change its
inappropriate relationship with the industry. The problems surrounding
pharmaceuticals are related to centralized, strict drug pricing control under the
universal health coverage. Although the current government attempts to facilitate
innovative research and development of novel therapeutics in Japan, further
reforms should be explored for patients who need new and emerging
pharmaceuticals.
PMID- 25848224
TI - Visual detection of glial cell line-derived neurotrophic factor based on a
molecular translator and isothermal strand-displacement polymerization reaction.
AB - BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) is a small protein
that potently promotes the survival of many types of neurons. Detection of GDNF
is vital to monitoring the survival of sympathetic and sensory neurons. However,
the specific method for GDNF detection is also un-discovered. The purpose of this
study is to explore the method for protein detection of GDNF. METHODS: A novel
visual detection method based on a molecular translator and isothermal strand
displacement polymerization reaction (ISDPR) has been proposed for the detection
of GDNF. In this study, a molecular translator was employed to convert the input
protein to output deoxyribonucleic acid signal, which was further amplified by
ISDPR. The product of ISDPR was detected by a lateral flow biosensor within 30
minutes. RESULTS: This novel visual detection method based on a molecular
translator and ISDPR has very high sensitivity and selectivity, with a dynamic
response ranging from 1 pg/mL to 10 ng/mL, and the detection limit was 1 pg/mL of
GDNF. CONCLUSION: This novel visual detection method exhibits high sensitivity
and selectivity, which is very simple and universal for GDNF detection to help
disease therapy in clinical practice.
PMID- 25848226
TI - Association of orthodontic treatment needs and oral health-related quality of
life.
PMID- 25848225
TI - Modeling, molecular dynamics, and docking assessment of transcription factor rho:
a potential drug target in Brucella melitensis 16M.
AB - The zoonotic disease brucellosis, a chronic condition in humans affecting renal
and cardiac systems and causing osteoarthritis, is caused by Brucella, a genus of
Gram-negative, facultative, intracellular pathogens. The mode of transmission and
the virulence of the pathogens are still enigmatic. Transcription regulatory
elements, such as rho proteins, play an important role in the termination of
transcription and/or the selection of genes in Brucella. Adverse effects of the
transcription inhibitors play a key role in the non-successive transcription
challenges faced by the pathogens. In the investigation presented here, we
computationally predicted the transcription termination factor rho (TtFRho)
inhibitors against Brucella melitensis 16M via a structure-based method. In view
the unknown nature of its crystal structure, we constructed a robust three
dimensional homology model of TtFRho's structure by comparative modeling with the
crystal structure of the Escherichia coli TtFRho (Protein Data Bank ID: 1PVO) as
a template in MODELLER (v 9.10). The modeled structure was optimized by applying
a molecular dynamics simulation for 2 ns with the CHARMM (Chemistry at HARvard
Macromolecular Mechanics) 27 force field in NAMD (NAnoscale Molecular Dynamics
program; v 2.9) and then evaluated by calculating the stereochemical quality of
the protein. The flexible docking for the interaction phenomenon of the template
consists of ligand-related inhibitor molecules from the ZINC (ZINC Is Not
Commercial) database using a structure-based virtual screening strategy against
minimized TtFRho. Docking simulations revealed two inhibitors compounds -
ZINC24934545 and ZINC72319544 - that showed high binding affinity among 2,829
drug analogs that bind with key active-site residues; these residues are
considered for protein-ligand binding and unbinding pathways via steered
molecular dynamics simulations. Arg215 in the model plays an important role in
the stability of the protein-ligand complex via a hydrogen bonding interaction by
aromatic-pi contacts, and the ADMET (absorption, distribution, metabolism, and
excretion) analysis of best leads indicate nontoxic in nature with good potential
for drug development.
PMID- 25848227
TI - The German version of the Individualized Care Scale - assessing validity and
reliability.
AB - AIM: To assess validity and reliability of the German version of the
Individualized Care Scale (ICS). BACKGROUND: Individualized nursing care plays a
pivotal role in establishing patient-centered care. To assess individualized
nursing care and to compare it in different settings and countries, valid and
reliable instruments are needed. No psychometric-tested instrument for comparing
individualized nursing care with other countries is available in Germany. DESIGN:
Cross-sectional study. METHODS: Data were collected between September 2013 and
June 2014 from 606 patients in 20 wards in five hospitals across Germany.
Unidimensionality of the ICS scales ICSA (patients' views on how individuality is
supported through nursing interventions) and ICSB (patients' perceptions of
individualized nursing care) was analyzed by confirmatory factor analysis.
Internal consistency was assessed by calculating Cronbach's alpha. The Smoliner
Scale (patients' perceptions of the decision-making process in nursing care) and
results from participating hospitals' assessment of the nursing care delivery
systems were used to assess known-groups validity and concurrent validity.
RESULTS: Fit indices of confirmatory factor analysis indicate unidimensionality
of the ICSA (Comparative Fit Index: 0.92; Tucker-Lewis Index: 0.902; root mean
square error of approximation: 0.09; standardized root mean square residual:
0.05) and the ICSB (Comparative Fit Index: 0.91; Tucker-Lewis Index: 0.89; root
mean square error of approximation: 0.09; standardized root mean square residual:
0.05). Internal consistency using Cronbach's alpha was 0.95 (95% confidence
interval: 0.94-0.95) for ICSA and 0.93 (95% confidence interval: 0.92-0.94) for
the ICSB. Concurrent validity was established by a significant relationship
between the Smoliner Scale and ICSA (r=0.66; P<0.01) and ICSB (r=0.72; P<0.01).
Known-groups validity was approved by ICSA/ICSB score differences related to
nursing care delivery systems and patients' perceptions of decision-making style.
CONCLUSION: The German version of the ICS is deemed a valid and reliable
instrument for use in practice and research with hospitalized patients.
PMID- 25848228
TI - Electronic health records and improved nursing management of chronic obstructive
pulmonary disease.
AB - This paper identifies evolving trends in the diagnosis and treatment of chronic
obstructive pulmonary disease (COPD), and recommends the integration of nursing
strategies in COPD management via widespread implementation of electronic health
records. COPD is a complex lung disease with diverse origins, both physical and
behavioral, manifested in a wide range of symptoms that further increase the
patient's risk for comorbidities. Early diagnosis and effective management of
COPD require monitoring of a dizzying array of COPD symptoms over extended
periods of time, and nurses are especially well positioned to manage potential
progressions of COPD, as frontline health care providers who obtain, record, and
organize patient data. Developments in medical technology greatly aid nursing
management of COPD, from the deployment of spirometry as a diagnostic tool at the
family practice level to newly approved treatment options, including non-nicotine
pharmacotherapies that reduce the cravings associated with tobacco withdrawal.
Among new medical technologies, electronic health records have proven
particularly advantageous in the management of COPD, enabling providers to
gather, maintain, and reference more patient data than has ever been possible
before. Thus, consistent and widespread implementation of electronic health
records facilitates the coordination of diverse treatment strategies, resulting
in increased positive health outcomes for patients with COPD.
PMID- 25848229
TI - Exploring barriers to the delivery of cervical cancer screening and early
treatment services in Malawi: some views from service providers.
AB - BACKGROUND: Cervical cancer is the most common reproductive health cancer in
Malawi. In most cases, women report to health facilities when the disease is in
its advanced stage. In this study, we investigate service providers' perceptions
about barriers for women to access cervical cancer screening and early treatment
services in Malawi. METHODS: We conducted in-depth interviews with 13 district
coordinators and 40 service providers of cervical cancer screening and early
treatment services in 13 districts in Malawi. The study was conducted in 2012.
The district coordinators helped the research team identify the health facilities
which were providing cervical cancer screening and early treatment services.
RESULTS: Almost all informants reported that cervical cancer was a major public
health problem in their districts and that prevention efforts for this disease
were being implemented. They were aware of the test and treat approach using
visual inspection with acetic acid (VIA). They, however, said that the delivery
of cervical cancer screening and early treatment services was compromised because
of factors such as gross shortage of staff, lack of equipment and supplies, the
lack of supportive supervision, and the use of male service providers. Informants
added that the lack of awareness about the disease among community members, long
distances to health facilities, the lack of involvement of husbands, and
prevailing misperceptions about the disease (eg, that it is caused by the
exposure to the VIA process) affect the uptake of these services. CONCLUSION:
While progress has been made in the provision of cervical cancer screening and
early treatment services in Malawi, a number of factors affect service delivery
and uptake. There is a need to continue creating awareness among community
members including husbands and also addressing identified barriers such as
shortage of staff and supplies in order to improve uptake of services.
PMID- 25848230
TI - Development of the CoMac Adherence DescriptorTM: a linguistically-based survey
for segmenting patients on their worldviews.
AB - Nonadherence to prescribed medication and healthy behaviors is a pressing health
care issue. Much research has been conducted in this area under a variety of
labels, such as compliance, disease management and, most recently, adherence.
However, the complex factors related to predicting and, more importantly,
understanding and explaining adherence, have nevertheless remained elusive.
However, through an in-depth linguistic analysis of patient talk, the
International Center for Intercultural Communication (ICIC) at Indiana University
has produced a psycholinguistic coding system that uses patients' own language to
cluster them into distinct groups based on their worldviews. ICIC's studies have
shown, for example, that patients reveal their fundamental perceptions about
themselves and their environment in their life narratives; clustering of
individual patients based on these different perceptions is possible via the use
of differential language in survey questions, and differential language can be
used to tailor messages for individual patients in a manner that these
individuals prefer over generically worded communication. In grant-funded
research, an interdisciplinary team of researchers at the ICIC reviewed the
literature and identified three basic psychosocial tenets related to adherence:
control orientation, based on locus of control research; agency, based on self
efficacy; and affect or attitude and emotion. These three constructs were
selected because, in the published literature, they have been consistently found
to be connected to patient adherence. Based on this research, a survey, the CoMac
DescriptorTM was developed. This report shows that The DescriptorTM questions and
responses are valid and reliable in segmenting patients across psychosocial
constructs, which will have positive implications for health care providers and
patients.
PMID- 25848231
TI - Simplicity, safety, and acceptability of insulin pen use versus the conventional
vial/syringe device in patients with type 1 and type 2 diabetes mellitus in
Lebanon.
AB - BACKGROUND: The aim of the study was to evaluate the simplicity, safety,
patients' preference, and convenience of the administration of insulin using the
pen device versus the conventional vial/syringe in patients with diabetes.
METHODS: This observational study was conducted in multiple community pharmacies
in Lebanon. The investigators interviewed patients with diabetes using an insulin
pen or conventional vial/syringe. A total of 74 questionnaires were filled over a
period of 6 months. Answers were entered into the Statistical Package for Social
Sciences (SPSS) software and Excel spreadsheet. t-test, logistic regression
analysis, and correlation analysis were used in order to analyze the results.
RESULTS: A higher percentage of patients from the insulin pen users group (95.2%)
found the method easy to use as compared to only 46.7% of the insulin
conventional users group (P 0.001, relative risk [RR]: 2.041, 95% confidence
interval [CI]: 1.178-3.535). Moreover, 61.9% and 26.7% of pen users and
conventional users, respectively, could read the scale easily (P 0.037, RR 2.321,
95% CI: 0.940-5.731), while 85.7% of pen users found it more convenient shifting
to pen and 86.7% of the conventional users would want to shift to pen if it had
the same cost. Pain perception was statistically different between the groups. A
much higher percentage (76.2%) of pen users showed no pain during injection
compared to only 26.7% of conventional users (P 0.003, RR 2.857, 95% CI: 1.194
6.838). CONCLUSION: The insulin pen was significantly much easier to use and less
painful than the conventional vial/syringe. Proper education on the methods of
administration/storage and disposal of needles/syringes is needed in both groups.
PMID- 25848232
TI - More than what the eye can see: the emotional journey and experience of
powerlessness of integrated care service users and their carers.
AB - PURPOSE: This article presents the emotional journey and experience of
powerlessness of integrated care service users and carers. MATERIALS AND METHODS:
The experiences of seven integrated care service users and carers affected by
complex conditions in a London borough were captured as video stories. The
integrated care service coordinated a system of health and social care: primary
care, community matrons, social workers, and the voluntary sector. The service
was designed to respond to identified cases of high-risk individuals with long
term, multiple, and age-related conditions needing preventive interventions. The
video stories were analyzed by researchers in collaboration with service users
using a visual thematic qualitative approach. This report is part of an
independent analysis of the integrated care service evaluation that used the
experience-based codesign model. RESULTS: The findings are presented in the
respective contexts of people with complex conditions and their carers. The
overwhelming feelings and emotions of both were loss of control and power
throughout their emotional journey, with family carers adopting a protective
attitude toward the patients. Their experience of powerlessness was variable
throughout their emotional journey. They were affected more strongly when in need
of extra help and support and while they were undergoing the process of receiving
extra services. When they were receiving help and support outside and within
hospitals, some participants were empowered, gaining skills and knowledge by
being provided with the mechanisms to cope with their condition at present and in
the future. CONCLUSION: Feelings of powerlessness were very common among
integrated care service users and their carers. Powerless/empowerment has been
poorly investigated to date. Visual methods and collaborative visual analysis
with service users have proved to be powerful methods too, but have been rarely
reported.
PMID- 25848233
TI - Skills-based medication training program for patients with schizophrenic
disorders: a rater-blind randomized controlled trial.
AB - BACKGROUND: The long-term course of schizophrenia is often characterized by
relapses, induced by poor medication adherence. Early nonadherence after
discharge is frequent. OBJECTIVE: To evaluate a skills-based inpatient training
program for medication intake. METHODS: We developed a manual-based inpatient
medication training program to be carried out by nurses and focusing on practical
skills enabling autonomous intake of medication. Medication adherence was
measured by three different methods: pill count, determination of serum levels,
and self-assessment by the patient. The raters were blinded. RESULTS: Four weeks
after discharge, 98% of the patients in the intervention group (N=52) were rated
as adherent by pill count versus 76% in the control group (N=50; P<0.01). By
measurement of serum level, 88.5% versus 70% were adherent (P<0.05). CONCLUSION:
The inpatient medication training program carried out by nurses seems to be an
effective intervention for enhancing medication adherence after hospital
discharge.
PMID- 25848234
TI - The epidemiology and management of postmenopausal osteoporosis: a viewpoint from
Brazil.
AB - Brazil has an aging population, with an associated increase in the prevalence of
chronic diseases. Postmenopausal osteoporosis is of particular concern because it
leads to an increased risk of fractures, with subsequent negative impacts on
health in older women. In recent years, efforts have been made to better
understand the epidemiology of osteoporosis in Brazil, and to manage both direct
and indirect costs to the Brazilian health care system. The reported prevalence
of osteoporosis among postmenopausal women in Brazil varies from 15% to 33%,
depending on the study methodology and the use of bone densitometry data or self
reporting by participants. A diagnosis of osteoporosis can be made on the basis
of fractures occurring without significant trauma or on the basis of low bone
mineral density measured by dual energy X-ray absorptiometry. To reduce the risk
of osteoporosis, all postmenopausal women should be encouraged to maintain a
healthy lifestyle, which includes physical activity and a balanced diet. Smoking
and alcohol use should also be addressed. Special attention should be given to
interventions to reduce the risk of falls, especially among older women. Calcium
intake should be encouraged, preferably through diet. The decision to recommend
calcium supplementation should be made individually because there is concern
about a possible increased risk of cardiovascular disease associated with this
treatment. Brazilian women obtain a minimal amount of vitamin D from their diet,
and supplementation is warranted in women with little exposure to solar
ultraviolet-B radiation. For women diagnosed with osteoporosis, some form of
pharmacologic therapy should be initiated. Compliance with treatment should be
monitored, and the treatment period should be individualized for each patient.
The Brazilian government provides medication for osteoporosis through the public
health system free of charge, but without proper epidemiological knowledge, the
implementation of public health programs is impaired.
PMID- 25848235
TI - Respiratory training as strategy to prevent cognitive decline in aging: a
randomized controlled trial.
AB - BACKGROUND: Inadequate oxygenation may cause lesions and brain atrophy during
aging. Studies show a positive association between pulmonary function and the
cognitive performance of individuals from middle age on. OBJECTIVE: To
investigate the effect of aerobic physical exercises and respiratory training on
the blood oxygenation, pulmonary functions, and cognition of the elderly. DESIGN:
This was a randomized and controlled trial with three parallel groups. A total of
195 community-dwelling elderly were assessed for eligibility; only n=102 were
included and allocated into the three groups, but after 6 months, n=68 were
analyzed in the final sample. Participants were randomized into a social
interaction group (the control group), an aerobic exercise group (the "walking"
group), or a respiratory training group (the "breathing" group). The main outcome
measures were the Wechsler Adult Intelligence Scale, Wechsler Memory Scale,
Wisconsin Card Sorting Test, respiratory muscular strength, cirtometry (thoracic
abdominal circumference); oxygen saturation in arterial blood (SpO2), and
hemogram. RESULTS: No differences were observed for any of the blood parameters.
Aerobic exercise and respiratory training were effective in improving the
pulmonary parameters. Better cognitive performance was observed for the breathing
group as regards abstraction and mental flexibility. The walking group remained
stable in the cognitive performance of most of the tests, except attention. The
control group presented worst performance in mental manipulation of information,
abstraction, mental flexibility, and attention. CONCLUSION: Our results showed
that both the walking and breathing groups presented improvement of pulmonary
function. However, only the breathing group showed improved cognitive function
(abstraction, mental flexibility). The improvement in cognitive functions cannot
be explained by blood parameters, such as SpO2, erythrocytes, hemoglobin, and
hematocrit.
PMID- 25848236
TI - Monocyte chemoattractant protein-1: a proinflammatory cytokine elevated in
sarcopenic obesity.
AB - OBJECTIVE: Sarcopenic obesity (SO) is associated with poorer physical outcomes
and functional status in the older adult. A proinflammatory milieu associated
with central obesity is postulated to enhance muscle catabolism. We set out to
examine associations of the chemokine monocyte chemoattractant protein-1 (MCP-1)
in groups of older adults, with sarcopenia, obesity, and the SO phenotypes.
METHODS: A total of 143 community dwelling, well, older adults were recruited.
Cross-sectional clinical data, physical performance, and muscle mass measurements
were collected. Obesity and sarcopenia were defined using revised National
Cholesterol Education Program (NCEP) obesity guidelines and those of the Asian
Working Group for Sarcopenia. Serum levels of MCP-1 were measured by enzyme
linked immunosorbent assay (ELISA). RESULTS: In all, 25.2% of subjects were
normal, 15.4% sarcopenic, 48.3% obese, and 11.2% were SO. The SO groups had the
lowest appendicular lean mass, highest percentage body fat, and lowest
performance scores on the Short Physical Performance Battery and grip strength.
The MCP-1 levels were significantly different, with the highest levels found in
SO participants (P<0.05). CONCLUSION: Significantly raised MCP-1 levels in obese
and SO subjects support the theory of chronic inflammation due to excess
adiposity. Longitudinal studies will reveal whether SO represents a continuum of
obesity causing accelerated sarcopenia and cardiovascular events, or the
coexistence of two separate conditions with synergistic effects affecting
functional performance.
PMID- 25848237
TI - Behavioral activation for dementia caregivers: scheduling pleasant events and
enhancing communications.
AB - BACKGROUND: Dementia caregiving is often associated with increase in depressive
symptoms and strained relationships. This study tested whether telephone
delivered psychoeducation combined with an enhanced behavioral activation (BA)
module had a better effect on the well-being of Alzheimer's caregivers than
psychoeducation alone. The focus is on enhancing the competent use of coping
skills via BA. The program is delivered by telephone to increase accessibility
and sustainability for caregivers. Senior citizens are trained as
paraprofessionals to deliver the BA module to increase the potential for
sustainability of the program. METHODS AND SUBJECTS: The study compared two
telephone interventions using a 4-month longitudinal randomized controlled trial.
For the first 4 weeks, all participants received the same psychoeducation program
via telephone. Then for the following 4 months, eight biweekly telephone follow
up calls were carried out. For these eight follow-up calls, participants were
randomized into either one of the two following groups with different conditions.
For the psychoeducation with BA (PsyED-BA) group, participants received eight
biweekly sessions of BA practice focused on pleasant event scheduling and
improving communications. For the psychoeducation only (PsyED only) group,
participants received eight biweekly sessions of general discussion of
psychoeducation and related information. A total of 62 family caregivers of
persons living with dementia were recruited and 59 (29 in the PsyED-BA group and
30 in the PsyED only group) completed the whole study. RESULTS: As compared to
the group with psychoeducation and discussion, the group with enhanced BA had
decreased levels of depressive symptoms. The study had a low attrition rate.
CONCLUSION: Results suggested that competence-based training could be effectively
administered through the telephone with the help of senior citizens trained and
engaged as paraprofessionals. Results contribute to the present literature by
offering some framework for developing effective, accessible, sustainable, and
less costly interventions.
PMID- 25848238
TI - Personalized therapeutics of alpha1-blockers in patients with lower urinary tract
symptoms suggestive of benign prostatic hyperplasia.
PMID- 25848239
TI - Cognitive fluctuations in connection to dysgraphia: a comparison of Alzheimer's
disease with dementia Lewy bodies.
AB - BACKGROUND: The purpose of the present study was to examine the relationship
between cognitive impairment and the performance of handwritten scripts presented
as "letter-writing" to a close relative by patients with dementia Lewy bodies
(DLB), as fluctuations of the symptoms phase, and in a matched group of patients
with Alzheimer's disease (AD). The degree of writing disability and personal,
spatial, and temporal orientation was compared in these two groups. DESIGN AND
METHODS: Fourteen simple questions, designed in a form that could be utilized by
any general practitioner in order to document the level of cognitive functioning
of each patient, were presented to 30 AD patients and 26 DLB patients. The
initial cognition test was designated PQ1. The patients were examined on tests of
letter-writing ability. Directly after the letter-writing, the list of 14
questions presented in PQ1 was presented again in a repeated procedure that was
designated PQ2. The difference between these two measures (PQ1 - PQ2) was
designated DDelta. This test of letter-writing ability and cognitive performance
was administered over 19 days. RESULTS: Several markedly strong relationships
between dysgraphia and several measures of cognitive performance in AD patients
and DLB patients were observed, but the deterioration of performance from PQ1 to
PQ2 over all test days were markedly significant in AD patients and not
significant in DLB patients. It is possible that in graphic expression even by
patients diagnosed with moderate to relatively severe AD and DLB there remains
some residual capacity for understanding and intention that may be expressed.
Furthermore, the deterioration in performance and the differences noted in AD and
DLB patients may be due to the different speed at which the process of the
protein degradation occurs for functional modification of synapses. CONCLUSION:
Our method can be used as part of neuropsychological tests to differentiate the
diagnosis between AD and DLB.
PMID- 25848240
TI - Repeated vertebral augmentation for new vertebral compression fractures of
postvertebral augmentation patients: a nationwide cohort study.
AB - PURPOSE: Postvertebral augmentation vertebral compression fractures are common;
repeated vertebral augmentation is usually performed for prompt pain relief. This
study aimed to evaluate the incidence and risk factors of repeat vertebral
augmentation. METHODS: We performed a retrospective, nationwide, population-based
longitudinal observation study, using the National Health Insurance Research
Database (NHIRD) of Taiwan. All patients who received vertebral augmentation for
vertebral compression fractures were evaluated. The collected data included
patient characteristics (demographics, comorbidities, and medication exposure)
and repeat vertebral augmentation. Kaplan-Meier and stratified Cox proportional
hazard regressions were performed for analyses. RESULTS: The overall incidence of
repeat vertebral augmentation was 11.3% during the follow-up until 2010. Patients
with the following characteristics were at greater risk for repeat vertebral
augmentation: female sex (AOR=1.24; 95% confidence interval [CI]: 1.10-2.36),
advanced age (AOR=1.60; 95% CI: 1.32-2.08), diabetes mellitus (AOR=4.31; 95% CI:
4.05-5.88), cerebrovascular disease (AOR=4.09; 95% CI: 3.44-5.76), dementia
(AOR=1.97; 95% CI: 1.69-2.33), blindness or low vision (AOR=3.72; 95% CI: 2.32
3.95), hypertension (AOR=2.58; 95% CI: 2.35-3.47), and hyperlipidemia (AOR=2.09;
95% CI: 1.67-2.22). Patients taking calcium/vitamin D (AOR=2.98; 95% CI: 1.83
3.93), bisphosphonates (AOR=2.11; 95% CI: 1.26-2.61), or calcitonin (AOR=4.59;
95% CI: 3.40-5.77) were less likely to undergo repeat vertebral augmentation;
however, those taking steroids (AOR=7.28; 95% CI: 6.32-8.08), acetaminophen
(AOR=3.54; 95% CI: 2.75-4.83), or nonsteroidal anti-inflammatory drugs (NSAIDs)
(AOR=6.14; 95% CI: 5.08-7.41) were more likely to undergo repeat vertebral
augmentation. CONCLUSION: We conclude that the incidence of repeat vertebral
augmentation is rather high. An understanding of risk factors predicting repeat
vertebral augmentation provides valuable basis to improve health care for
geriatric populations.
PMID- 25848241
TI - Home-based pulmonary rehabilitation improves clinical features and systemic
inflammation in chronic obstructive pulmonary disease patients.
AB - Chronic obstructive pulmonary disease (COPD) is a respiratory disease
characterized by chronic airflow limitation that leads beyond the pulmonary
changes to important systemic effects. COPD is characterized by pulmonary and
systemic inflammation. However, increases in the levels of inflammatory cytokines
in plasma are found even when the disease is stable. Pulmonary rehabilitation
improves physical exercise capacity and quality of life and decreases dyspnea.
The aim of this study was to evaluate whether a home-based pulmonary
rehabilitation (HBPR) program improves exercise tolerance in COPD patients, as
well as health-related quality of life and systemic inflammation. This
prospective study was conducted at the Laboratory of Functional Respiratory
Evaluation, Nove de Julho University, Sao Paulo, Brazil. After anamnesis,
patients were subjected to evaluations of health-related quality of life and
dyspnea, spirometry, respiratory muscle strength, upper limbs incremental test,
incremental shuttle walk test, and blood test for quantification of systemic
inflammatory markers (interleukin [IL]-6 and IL-8). At the end of the
evaluations, patients received a booklet containing the physical exercises to be
performed at home, three times per week for 8 consecutive weeks. Around 25
patients were enrolled, and 14 completed the pre- and post-HBPR ratings. There
was a significant increase in the walked distance and the maximal inspiratory
pressure, improvements on two components from the health-related quality-of-life
questionnaire, and a decrease in plasma IL-8 levels after the intervention. The
HBPR is an important and viable alternative to pulmonary rehabilitation for the
treatment of patients with COPD; it improves exercise tolerance, inspiratory
muscle strength, quality of life, and systemic inflammation in COPD patients.
PMID- 25848242
TI - COPD and its association with smoking in the Mainland China: a cross-sectional
analysis of 0.5 million men and women from ten diverse areas.
AB - PURPOSE: In adult Chinese men, smoking prevalence is high, but little is known
about its association with chronic respiratory disease, which is still poorly
diagnosed and managed. METHODS: A nationwide study recruited 0.5 million men and
women aged 30-79 years during 2004-2008 from ten geographically diverse areas
across the Mainland China. Information was collected from each participant
regarding smoking and self-reported physician diagnosis of chronic
bronchitis/emphysema (CB/E), along with measurement of lung function indices.
Logistic regression was used to yield sex-specific odds ratios (ORs) relating
smoking to airflow obstruction (AFO), defined as forced expiratory volume in 1
second (FEV1)/forced vital capacity (FVC) <0.7 and CB/E, adjusting for age,
areas, education, and income. RESULTS: Overall 74% of men were ever regular
smokers; among them, 7.2% had AFO compared with 5.4% in never-smokers, yielding
an OR of 1.42 (95% confidence interval [CI]: 1.34-1.50). The risk was strongly
associated with amount smoked and starting to smoke at a younger age. Among ex
smokers, the OR was more extreme for those who had quit due to illness (OR: 1.86,
95% CI: 1.77-1.96) than those who had quit by choice (OR:1.08, 95% CI: 1.01
1.16). CB/E prevalence was also significantly elevated in ex-smokers who had quit
because of ill health (OR:2.79, 95% CI: 2.64-2.95), but not in regular smokers
(OR:1.04, 95% CI: 0.96-1.11). Female smokers was rare (3%), but carried an excess
risk for AFO (OR:1.53, 95% CI: 1.43-1.65) and, to a lesser extent, for CB/E
(OR:1.28, 95% CI: 1.15-1.42). CONCLUSION: In Mainland China, adult smokers,
particularly ex-smokers who had quit because of illness, had significantly higher
prevalence of chronic respiratory disease. AFO appeared to be more strongly
associated with smoking than self-reported chronic respiratory disease.
PMID- 25848244
TI - Clinical potential of aclidinium bromide in chronic obstructive pulmonary
disease.
AB - Three long-acting muscarinic antagonists (LAMAs) are now available in Europe,
providing clinicians and patients with a choice of interventions, which is
important in COPD, which is clinically a heterogeneous disease. The first LAMA,
tiotropium, has been widely used over the last decade as a once-daily maintenance
therapy in stable COPD to improve patients' health-related quality of life and to
reduce the risk of exacerbations. Administered via the HandiHaler((r)) device, it
is safe and well tolerated. Another new once-daily LAMA, glycopyrronium, has also
been shown to improve health status and reduce exacerbations, and is well
tolerated. The subject of this review is a third LAMA, aclidinium bromide, which
was approved as a twice-daily maintenance bronchodilator treatment. In the
pivotal Phase III clinical trials, patients receiving aclidinium achieved
significantly greater improvements in lung function, reductions in
breathlessness, and improvements in health status compared with placebo, for up
to 24 weeks. In continuation studies, these improvements were sustained for up to
52 weeks. Pooled data showed exacerbation frequency was significantly reduced
with aclidinium versus placebo. Preclinical and pharmacological studies
demonstrating low systemic bioavailability and a low propensity to induce cardiac
arrhythmias were translated into a favorable tolerability profile in the clinical
trial program - the adverse event profile of aclidinium was similar to placebo,
with a low incidence of anticholinergic and cardiac adverse events. While
additional studies are needed to evaluate its full clinical potential, aclidinium
is an important part of this recent expansion of LAMA therapeutic options,
providing clinicians and patients with an effective and well-tolerated COPD
treatment.
PMID- 25848243
TI - A bibliometric analysis of the 100 most influential papers on COPD.
AB - OBJECTIVE: We aimed to identify the 100 top-cited articles published on chronic
obstructive pulmonary disease (COPD) and to analyze their characteristics so as
to provide information on the achievement and development in COPD research over
the past decades. METHODS AND MATERIALS: A comprehensive list of citation
classics in COPD was generated by searching the Science Citation Index expanded
database, using the keywords "COPD" or "chronic obstructive pulmonary disease" or
"chronic obstructive pulmonary diseases". The 100 top-cited research papers were
retrieved by reading the abstract or full text if needed. All eligible articles
were read for basic information, including country of origin, organizations,
article type, journals, research field, and authors. RESULTS: The 100 top-cited
articles on COPD were published between 1966 and 2010. The number of citations
ranged from 254 to 2,164, with a mean of 450 citations for each article. These
citation classics were from 32 countries, with 38 from the United States. The
Imperial College London led the list of classics, with 16 papers. The 100 top
cited articles were distributed in 18 journals, with the American Journal of
Respiratory, Critical Care Medicine, and Journal of the American Medical
Association topping the list. Among the various fields, both respiratory system
(63%) and general internal medicine (63%) were the most common fields of study
for the 100 articles. CONCLUSION: Our bibliometric analysis provides a historical
perspective on the progress of scientific research on COPD. Articles originating
from the United States and published in high-impact specialized respiratory
journals are most likely to be cited in the field of COPD research.
PMID- 25848245
TI - Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary
disease: a link to bacterial colonization?
AB - We examined whether systemic cytokine signaling via interleukin (IL)-17 and
growth-related oncogene-alpha (GRO-alpha) is impaired in smokers with obstructive
pulmonary disease including chronic bronchitis (OPD-CB). We also examined how
this systemic cytokine signaling relates to bacterial colonization in the airways
of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60,
corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD]
stage I-IV) underwent recurrent blood and sputum sampling over 60 weeks, during
stable conditions and at exacerbations. We characterized cytokine protein
concentrations in blood and bacterial growth in sputum. Asymptomatic smokers
(n=10) and never-smokers (n=10) were included as control groups. During stable
clinical conditions, the protein concentrations of IL-17 and GRO-alpha were
markedly lower among OPD-CB patients compared with never-smoker controls, whereas
the asymptomatic smoker controls displayed intermediate concentrations. Notably,
among OPD-CB patients, colonization by opportunistic pathogens was associated
with markedly lower IL-17 and GRO-alpha, compared with colonization by common
respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB
patients, GRO-alpha and neutrophil concentrations were increased, whereas protein
concentrations and messenger RNA for IL-17 were not detectable in a reproducible
manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO
alpha is impaired and this alteration may be linked to colonization by
opportunistic pathogens in the airways. Given the potential pathogenic and
therapeutic implications, these findings deserve to be validated in new and
larger patient cohorts.
PMID- 25848246
TI - Effectiveness of bronchoscopic lung volume reduction using unilateral
endobronchial valve: a systematic review and meta-analysis.
AB - BACKGROUND: Bronchoscopic lung volume reduction (BLVR) can be suggested as an
alternative for surgical lung volume reduction surgery for severe emphysema
patients. This article intends to evaluate by systematic review the safety and
effectiveness of BLVR using a one-way endobronchial valve. METHODS: A systematic
search of electronic databases, including MEDLINE, EMBASE, and the Cochrane
Library, as well as eight domestic databases up to December 2013, was performed.
Two reviewers independently screened all references according to selection
criteria. The Scottish Intercollegiate Guidelines Network criterion was used to
assess quality of literature. Data from randomized controlled trials were
combined and meta-analysis was performed. RESULTS: This review included 15
studies. Forced expiratory volume in 1 second (FEV1) improved in the intervention
group compared with the control group (mean difference [MD]=6.71, 95% confidence
interval [CI]: 3.31-10.11). Six-minute walking distance (MD=15.66, 95% CI: 1.69
29.64) and cycle workload (MD=4.43, 95% CI: 1.80-7.07) also improved. In
addition, St George's Respiratory Questionnaire score decreased (MD=4.29, 95% CI:
-6.87 to -1.71) in the intervention group. In a subgroup analysis of patients
with complete fissure, the FEV1 change from baseline was higher in the BLVR group
than in the control group for both 6 months (MD=15.28, P<0.001) and 12 months
(MD=17.65, P<0.001), whereas for patients with incomplete fissure, FEV1 and 6
minute walking distance showed no change. One-year follow-up randomized
controlled trials reported deaths, although the cause of death was not related to
BLVR. Respiratory failure and pneumothorax incidence rates were relatively higher
in the BLVR group, but the difference was not significant. CONCLUSION: BLVR may
be an effective and safe procedure for the treatment of severe COPD patients with
emphysema, based on existing studies.
PMID- 25848247
TI - Modafinil: a novel alternative to non-invasive ventilation in hypercapnic
respiratory failure?
PMID- 25848248
TI - Novel PLGA-based nanoparticles for the oral delivery of insulin.
AB - BACKGROUND: Insulin is the drug therapy for patients with insulin-dependent
diabetes mellitus. A number of attempts have been made in the past to overcome
the problems associated with the oral delivery of insulin, but with little
success. Orally administered insulin has encountered with many difficulties such
as rapid degradation and poor intestinal absorption. The potential use of D-alpha
tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene
glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was
investigated for sustained delivery of insulin (IS). OBJECTIVE: To investigate
the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential
drug carrier for the oral delivery of insulin. METHODS: A series of biodegradable
low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were
synthesized by melt polycondensation. The commercial insulin-loaded TPGS
emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water-oil-water
emulsion solvent evaporation method. The physical and chemical properties of PLGA
copolymers, particle size, zeta potential, and morphology of the NPs were
examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by
oral administration. RESULTS: The maximum encapsulation efficiency of ISTPPLG6
NPs was 78.6% +/- 1.2%, and the mean diameter of the NPs was 180 +/- 20 nm. The
serum glucose level was significantly (twofold) decreased on treatment with
ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30)
NPs when compared to that of free insulin-treated diabetic rats. The results show
that the oral administration of ISTPPLG6 NPs is an effective method of reducing
serum glucose level for a period of 24 hours. Histopathological studies reveal
that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver,
kidneys, and pancreas, indicating its biocompatibility and regenerative effects.
CONCLUSION: ISTPPLG6 NPs can act as potential drug carriers for the oral delivery
of insulin.
PMID- 25848249
TI - Silica nanoparticles increase human adipose tissue-derived stem cell
proliferation through ERK1/2 activation.
AB - BACKGROUND: Silicon dioxide composites have been found to enhance the mechanical
properties of scaffolds and to support growth of human adipose tissue-derived
stem cells (hADSCs) both in vitro and in vivo. Silica (silicon dioxide alone)
exists as differently sized particles when suspended in culture medium, but it is
not clear whether particle size influences the beneficial effect of silicon
dioxide on hADSCs. In this study, we examined the effect of different sized
particles on growth and mitogen-activated protein kinase signaling in hADSCs.
METHODS: Silica gel was prepared by a chemical reaction using hydrochloric acid
and sodium silicate, washed, sterilized, and suspended in serum-free culture
medium for 48 hours, and then sequentially filtered through a 0.22 MUm filter
(filtrate containing nanoparticles smaller than 220 nm; silica NPs). hADSCs were
incubated with silica NPs or 3 MUm silica microparticles (MPs), examined by
transmission electron microscopy, and assayed for cell proliferation, apoptosis,
and mitogen-activated protein kinase signaling. RESULTS: Eighty-nine percent of
the silica NPs were around 50-120 nm in size. When hADSCs were treated with the
study particles, silica NPs were observed in endocytosed vacuoles in the cytosol
of hADSCs, but silica MPs showed no cell entry. Silica NPs increased the
proliferation of hADSCs, but silica MPs had no significant effect in this regard.
Instead, silica MPs induced slight apoptosis. Silica NPs increased
phosphorylation of extracellular signal-related kinase (ERK)1/2, while silica MPs
increased phosphorylation of p38. Silica NPs had no effect on phosphorylation of
Janus kinase or p38. Pretreatment with PD98059, a MEK inhibitor, prevented the
ERK1/2 phosphorylation and proliferation induced by silica NPs. CONCLUSION:
Scaffolds containing silicon dioxide for tissue engineering may enhance cell
growth through ERK1/2 activation only when NPs around 50-120 nm in size are
included, and single component silica-derived NPs could be useful for
bioscaffolds in stem cell therapy.
PMID- 25848250
TI - The fate of calcium carbonate nanoparticles administered by oral route:
absorption and their interaction with biological matrices.
AB - BACKGROUND: Orally administered particles rapidly interact with biological fluids
containing proteins, enzymes, electrolytes, and other biomolecules to eventually
form particles covered by a corona, and this corona potentially affects particle
uptake, fate, absorption, distribution, and elimination in vivo. This study
explored relationships between the biological interactions of calcium carbonate
particles and their biokinetics. METHODS: We examined the effects of food grade
calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]:
specific surface areas of 15.8 and 0.83 m(2)/g, respectively) on biological
interactions in in vitro simulated physiological fluids, ex vivo biofluids, and
in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution
of calcium carbonates were evaluated following a single dose oral administration
to rats. RESULTS: N-Cal interacted more with biomatrices than bulk materials in
vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did
not interact more actively with biomatrices in vivo. Analysis of coronas revealed
that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major
corona proteins, regardless of particle size. A biokinetic study revealed that
orally delivered N-Cal was more rapidly absorbed into the blood stream than B
Cal, but no significant differences were observed between the two in terms of
absorption efficiencies or tissue distributions. Both calcium carbonates were
primarily present as particulate forms in gastrointestinal fluids but enter the
circulatory system in dissolved Ca(2+), although both types showed partial phase
transformation to dicalcium phosphate dihydrate. Relatively low dissolution
(about 4%), no remarkable protein-particle interaction, and the major particulate
fate of calcium carbonate in vivo gastrointestinal fluids can explain its low
oral absorption (about 4%) regardless of particle size. CONCLUSION: We conclude
that calcium carbonate nanoparticles can act more actively with biological
matrices in vitro and ex vivo, but that in vivo, their biological interactions
and biokinetics are not affected by particle size.
PMID- 25848251
TI - Comparison of two self-assembled macromolecular prodrug micelles with different
conjugate positions of SN38 for enhancing antitumor activity.
AB - 7-Ethyl-10-hydroxycamptothecin (SN38), an active metabolite of irinotecan (CPT
11), is a remarkably potent antitumor agent. The clinical application of SN38 has
been extremely restricted by its insolubility in water. In this study, we
successfully synthesized two macromolecular prodrugs of SN38 with different
conjugate positions (chitosan-(C10-OH)SN38 and chitosan-(C20-OH)SN38) to improve
the water solubility and antitumor activity of SN38. These prodrugs can self
assemble into micelles in aqueous medium. The particle size, morphology, zeta
potential, and in vitro drug release of SN38 and its derivatives, as well as
their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a
xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OH)SN38 (CS
(10s)SN38) and chitosan-(C20-OH) SN38 (CS-(20s)SN38) were 13.3- and 25.9-fold
more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26,
respectively. The area under the curve (AUC)0-24 of SN38 after intravenously
administering CS-(10s)SN38 and CS-(20s)SN38 to Sprague Dawley rats was greatly
improved when compared with CPT-11 (both P<0.01). A larger AUC0-24 of CS
(20s)SN38 was observed when compared to CS-(10s)SN38 (P<0.05). Both of the novel
self-assembled chitosan-SN38 prodrugs demonstrated superior anticancer activity
to CPT-11 in the CT26 xenograft BALB/c mouse model. We have also investigated the
differences between these macromolecular prodrug micelles with regards to
enhancing the antitumor activity of SN38. CS-(20s)SN38 exhibited better in vivo
antitumor activity than CS-(10s)SN38 at a dose of 2.5 mg/kg (P<0.05). In
conclusion, both macromolecular prodrug micelles improved the in vivo conversion
rate and antitumor activity of SN38, but the prodrug in which C20-OH was
conjugated to macromolecular materials could be a more promising platform for
SN38 delivery.
PMID- 25848252
TI - A hybrid substratum for primary hepatocyte culture that enhances hepatic
functionality with low serum dependency.
AB - Cell culture systems have proven to be crucial for the in vitro maintenance of
primary hepatocytes and the preservation of hepatic functional expression at a
high level. A poly-(N-p-vinylbenzyl-4-O-beta-D-galactopyranosyl-D-gluconamide)
matrix can recognize cells and promote liver function in a spheroid structure
because of a specific galactose-asialoglycoprotein receptor interaction.
Meanwhile, a fusion protein, E-cadherin-Fc, when incubated with various cells,
has shown an enhancing effect on cellular viability and metabolism. Therefore, a
hybrid substratum was developed for biomedical applications by using both of
these materials to combine their advantages for primary hepatocyte cultures. The
isolated cells showed a monolayer aggregate morphology on the coimmobilized
surface and displayed higher functional expression than cells on traditional
matrices. Furthermore, the hybrid system, in which the highest levels of cell
adhesion and hepatocellular metabolism were achieved with the addition of 1%
fetal bovine serum, showed a lower serum dependency than the collagen/gelatin
coated surface. Accordingly, this substrate may attenuate the negative effects of
serum and further contribute to establishing a defined culture system for primary
hepatocytes.
PMID- 25848253
TI - Water-soluble L-cysteine-coated FePt nanoparticles as dual MRI/CT imaging
contrast agent for glioma.
AB - Nanoparticles (NPs) are advantageous for the delivery of diagnosis agents to
brain tumors. In this study, we attempted to develop an L-cysteine coated FePt
(FePt-Cys) NP as MRI/CT imaging contrast agent for the diagnosis of malignant
gliomas. FePt-Cys NPs were synthesized through a co-reduction route, which was
characterized by transmission electron microscopy, high-resolution transmission
electron microscopy, powder X-ray diffraction, Fourier transform infrared
spectroscopy, and dynamic light scattering. The MRI and CT imaging ability of
FePt-Cys NPs was evaluated using different gliomas cells (C6, SGH44, U251) as the
model. Furthermore, the biocompatibility of the as-synthesized FePt-Cys NPs was
evaluated using three different cell lines (ECV304, L929, and HEK293) as the
model. The results showed that FePt-Cys NPs displayed excellent biocompatibility
and good MRI/CT imaging ability, thereby indicating promising potential as a dual
MRI/CT contrast agent for the diagnosis of brain malignant gliomas.
PMID- 25848254
TI - Chitosan/siRNA functionalized titanium surface via a layer-by-layer approach for
in vitro sustained gene silencing and osteogenic promotion.
AB - Titanium surface modification is crucial to improving its bioactivity, mainly its
bone binding ability in bone implant materials. In order to functionalize
titanium with small interfering RNA (siRNA) for sustained gene silencing in
nearby cells, the layer-by-layer (LbL) approach was applied using sodium
hyaluronate and chitosan/siRNA (CS/siRNA) nanoparticles as polyanion and
polycation, respectively, to build up the multilayered film on smooth titanium
surfaces. The CS/siRNA nanoparticle characterization was analyzed first. Dynamic
contact angle, atomic force microscopy, and scanning electron microscopy were
used to monitor the layer accumulation. siRNA loaded in the film was quantitated
and the release profile of film in phosphate-buffered saline was studied. In
vitro knockdown effect and cytotoxicity evaluation of the film were investigated
using H1299 human lung carcinoma cells expressing green fluorescent protein
(GFP). The transfection of human osteoblast-like cell MG63 and H1299 were
performed and the osteogenic differentiation of MG63 on LbL film was analyzed.
The CS/siRNA nanoparticles exhibited nice size distribution. During formation of
the film, the surface wettability, topography, and roughness were alternately
changed, indicating successful adsorption of the individual layers. The scanning
electron microscope images clearly demonstrated the hybrid structure between
CS/siRNA nanoparticles and sodium hyaluronate polymer. The cumulated load of
siRNA increased linearly with the bilayer number and, more importantly, a gradual
release of the film allowed the siRNA to be maintained on the titanium surface
over approximately 1 week. In vitro transfection revealed that the LbL film
associated siRNA could consistently suppress GFP expression in H1299 without
showing significant cytotoxicity. The LbL film loading with osteogenic siRNA
could dramatically increase the osteogenic differentiation in MG63. In
conclusion, LbL technology can potentially modify titanium surfaces with specific
gene-regulatory siRNAs to enhance biofunction.
PMID- 25848255
TI - Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial
phototherapy.
AB - We report a novel cancer-targeted nanomedicine platform for imaging and prospect
for future treatment of unresected ovarian cancer tumors by intraoperative
multimodal phototherapy. To develop the required theranostic system, novel low
oxygen graphene nanosheets were chemically modified with polypropylenimine
dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular
design prevents fluorescence quenching of the Pc by graphene nanosheets,
providing the possibility of fluorescence imaging. Furthermore, the developed
nanoplatform was conjugated with poly(ethylene glycol), to improve
biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide,
for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation
of single wavelength was used for both heat generation by the graphene nanosheets
(photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by
Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an
enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%-95%
at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to
the synergistic effects of generated ROS and mild hyperthermia. An animal study
confirmed that Pc loaded into the nanoplatform can be employed as a NIR
fluorescence agent for imaging-guided drug delivery. Hence, the newly developed
Pc-graphene nanoplatform has the significant potential as an effective NIR
theranostic probe for imaging and combinatorial phototherapy.
PMID- 25848256
TI - Fluoromica nanoparticle cytotoxicity in macrophages decreases with size and
extent of uptake.
AB - Polyurethanes are widely used in biomedical devices such as heart valves,
pacemaker leads, catheters, vascular devices, and surgical dressings because of
their excellent mechanical properties and good biocompatibility. Layered silicate
nanoparticles can significantly increase tensile strength and breaking strain of
polyurethanes potentially increasing the life span of biomedical devices that
suffer from wear in vivo. However, very little is known about how these
nanoparticles interact with proteins and cells and how they might exert unwanted
effects. A series of fluoromica nanoparticles ranging in platelet size from 90 to
over 600 nm in diameter were generated from the same base material ME100 by high
energy milling and differential centrifugation. The cytotoxicity of the resulting
particles was dependent on platelet size but in a manner that is opposite to many
other types of nanomaterials. For the fluoromicas, the smaller the platelet size,
the less toxicity was observed. The small fluoromica nanoparticles (<200 nm) were
internalized by macrophages via scavenger receptors, which was dependent on the
protein corona formed in serum. This internalization was associated with
apoptosis in RAW cells but not in dTHP-1 cells. The larger particles were not
internalized efficiently but mostly decorated the surface of the cells, causing
membrane disruption, even in the presence of 80% serum. This work suggests the
smaller fluoromica platelets may be safer for use in humans but their propensity
to recognize macrophage scavenger receptors also suggests that they will target
the reticulo-endoplasmic system in vivo.
PMID- 25848257
TI - Mechanism of enhanced antiosteoporosis effect of circinal-icaritin by self
assembled nanomicelles in vivo with suet oil and sodium deoxycholate.
AB - BACKGROUND: Circinal-icaritin (CIT), one new active aglycone of Epimedium, can
exert a beneficial effect on osteoporotic bone. However, its low bioavailability
limits its clinical efficacy for the treatment of osteoporosis. MATERIALS AND
METHODS: In this paper, suet oil (SO) was used to improve the oral
bioavailability of CIT and enhance its antiosteoporosis effect and absorption.
After oral administration of CIT together with SO, the CIT and SO self-assembled
into nanomicelles under the action of sodium deoxycholate (DOC) by bile
secretion. The antiosteoporosis effects of the CIT-SO-DOC nanomicelles were
evaluated in osteoporotic rats by bone mineral density, serum biochemical
markers, bone microarchitecture, bone biomechanical properties, and related
protein and gene expressions. We examined the bioavailability of CIT and its
nanomicelles in vivo, and subsequently the nanomicelles were verified using
transmission electron microscopy. Finally, we evaluated absorption across a rat
intestinal perfusion model. RESULTS: Compared with CIT, in the CIT-SO groups,
protein and messenger ribonucleic acid expressions of osteoprotegerin were
increased, while expressions of receptor activator of nuclear factor-kappaB
ligand in bone tissue were decreased; bone-turnover markers in serum of
hydroxyproline, alkaline phosphatase, tartrate-resistant acid phosphatase 5b, and
receptor activator of nuclear factor-kappaB ligand levels were decreased, while
osteoprotegerin and osteocalcin levels were increased; and trabecular bone mass,
microarchitecture, and bone biomechanical strength were enhanced. The relative
bioavailabilities of CIT-SO high dosage, CIT-SO medium dosage, and CIT-SO low
dosage (area under concentration-time curve [AUC]0-infinity) compared with that
of raw CIT high dosage, CIT medium dosage, and CIT low dosage (AUC0-infinity)
were 127%, 121%, and 134%, respectively. The average particle size of CIT-DOC was
significantly decreased after adding SO (P<0.01), and the intestinal permeability
coefficients of CIT-SO-DOC nanomicelles in the duodenum, jejunum, ileum, and
colon were all significantly improved (P<0.01). CONCLUSION: The increased
antiosteoporosis effects and bioavailability of CIT-SO-DOC self-assembled
nanomicelles were due to an increase in absorption of CIT by reducing the
particle sizes of CIT. SO may be a practical oral carrier for antiosteoporosis
drugs with low bioavailability.
PMID- 25848258
TI - Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel
transition studies, dissolution-release kinetics, in vitro toxicity, and
pharmacological evaluation.
AB - In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL
188, were studied with regard to the physicochemical aspects of sol-gel
transition and pharmaceutical formulation issues such as dissolution-release
profiles. In particular, we evaluated the cytotoxicity, genotoxicity, and in vivo
pharmacological performance of PL 407 and PL 407-PL 188 hydrogels containing
tramadol (TR) to analyze its potential treatment of acute pain. Drug-micelle
interaction studies showed the formation of PL 407-PL 188 binary systems and the
drug partitioning into the micelles. Characterization of the sol-gel transition
phase showed an increase on enthalpy variation values that were induced by the
presence of TR hydrochloride within the PL 407 or PL 407-PL 188 systems. Hydrogel
dissolution occurred rapidly, with approximately 30%-45% of the gel dissolved,
reaching ~80%-90% up to 24 hours. For in vitro release assays, formulations
followed the diffusion Higuchi model and lower K(rel) values were observed for PL
407 (20%, K(rel) = 112.9 +/- 10.6 MUg . h(-1/2)) and its binary systems PL 407-PL
188 (25%-5% and 25%-10%, K(rel) =80.8 +/- 6.1 and 103.4 +/- 8.3 MUg . h(-1/2),
respectively) in relation to TR solution (K(rel) =417.9 +/- 47.5 MUg . h(-1/2),
P<0.001). In addition, the reduced cytotoxicity (V79 fibroblasts and hepatocytes)
and genotoxicity (V79 fibroblasts), as well as the prolonged analgesic effects
(>72 hours) pointed to PL-based hydrogels as a potential treatment, by
subcutaneous injection, for acute pain.
PMID- 25848259
TI - Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of
silymarin in rats with Roux-en-Y gastric bypass surgery.
AB - Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of
obese patients. Although food intake is restricted by RYGB, drug absorption is
also decreased. The purpose of this study was to develop novel self
nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of
silymarin, which has poor water solubility. The SNEDDS were characterized by
size, zeta potential, droplet number, and morphology. A technique of RYGB was
performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of
600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous
suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main
active ingredient in silymarin, was chosen for estimating the pharmacokinetic
parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of
190 nm with a spherical shape. The nanocarriers promoted silibinin availability
via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the
suspension and PEG 400 solution, respectively. A significant double-peak
concentration of silibinin was detected for RYGB rats receiving SNEDDS.
Fluorescence imaging showed a deeper and broader penetration of Nile red, the
fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400
solution. Histological examination showed that SNEDDS caused more minor
inflammation at the gastrointestinal membrane as compared with that caused by PEG
400 solution, indicating a shielding of direct silymarin contact with the mucosa
by the nanodroplets. SNEDDS generally showed low-level or negligible irritation
in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully
developed to improve the dissolution, permeability, and oral bioavailability of
silymarin. To the best of our knowledge, this is the first investigation
reporting the usefulness of SNEDDS for improving drug malabsorption elicited by
gastric bypass surgery.
PMID- 25848260
TI - Docetaxel-loaded solid lipid nanoparticles as a basis for a targeted and dose
sparing personalized breast cancer treatment strategy.
PMID- 25848261
TI - Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and
osteosarcoma cells.
AB - Cells respond to their surroundings through an interactive adhesion process that
has direct effects on cell proliferation and migration. This research was
designed to investigate the effects of TiO2 nanotubes with different topographies
and structures on the biological behavior of cultured cells. The results
demonstrated that the nanotube diameter, rather than the crystalline structure of
the coatings, was a major factor for the biological behavior of the cultured
cells. The optimal diameter of the nanotubes was 20 nm for cell adhesion,
migration, and proliferation in both glioma and osteosarcoma cells. The
expression levels of vitronectin and phosphor-focal adhesion kinase were affected
by the nanotube diameter; therefore, it is proposed that the responses of
vitronectin and phosphor-focal adhesion kinase to the nanotube could modulate
cell fate. In addition, the geometry and size of the nanotube coating could
regulate the degree of expression of acetylated alpha-tubulin, thus indirectly
modulating cell migration behavior. Moreover, the expression levels of apoptosis
associated proteins were influenced by the topography. In conclusion, a nanotube
diameter of 20 nm was the critical threshold that upregulated the expression
level of Bcl-2 and obviously decreased the expression levels of Bax and caspase
3. This information will be useful for future biomedical and clinical
applications.
PMID- 25848262
TI - Alendronate-coated long-circulating liposomes containing 99mtechnetium
ceftizoxime used to identify osteomyelitis.
AB - Osteomyelitis is a progressive destruction of bones caused by microorganisms.
Inadequate or absent treatment increases the risk of bone growth inhibition,
fractures, and sepsis. Among the diagnostic techniques, functional images are the
most sensitive in detecting osteomyelitis in its early stages. However, these
techniques do not have adequate specificity. By contrast, radiolabeled
antibiotics could improve selectivity, since they are specifically recognized by
the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery
systems with high affinity for bones could improve the overall uptake. In this
work, long-circulating and alendronate-coated liposomes containing
(99m)technetium-radiolabeled ceftizoxime were prepared and their ability to
identify infectious foci (osteomyelitis) in animal models was evaluated. The
effect of the presence of PEGylated lipids and surface-attached alendronate was
evaluated. The bone-targeted long-circulating liposomal (99m)technetium
ceftizoxime showed higher uptake in regions of septic inflammation than did the
non-long-circulating and/or alendronate-non-coated liposomes, showing that both
the presence of PEGylated lipids and alendronate coating are important to
optimize the bone targeting. Scintigraphic images of septic or aseptic
inflammation-bearing Wistar rats, as well as healthy rats, were acquired at
different time intervals after the intravenous administration of these liposomes.
The target-to-non-target ratio proved to be significantly higher in the
osteomyelitis-bearing animals for all investigated time intervals.
Biodistribution studies were also performed after the intravenous administration
of the formulation in osteomyelitis-bearing animals. A significant amount of
liposomes were taken up by the organs of the mononuclear phagocyte system (liver
and spleen). Intense renal excretion was also observed during the entire
experiment period. Moreover, the liposome uptake by the infectious focus was
significantly high. These results show that long-circulating and alendronate
coated liposomes containing (99m)technetium-radiolabeled ceftizoxime have a
tropism for infectious foci.
PMID- 25848263
TI - Graphene-based nanovehicles for photodynamic medical therapy.
AB - Graphene and its derivatives such as graphene oxide (GO) have been widely
explored as promising drug delivery vehicles for improved cancer treatment. In
this review, we focus on their applications in photodynamic therapy. The large
specific surface area of GO facilitates efficient loading of the photosensitizers
and biological molecules via various surface functional groups. By incorporation
of targeting ligands or activatable agents responsive to specific biological
stimulations, smart nanovehicles are established, enabling tumor-triggering
release or tumor-selective accumulation of photosensitizer for effective therapy
with minimum side effects. Graphene-based nanosystems have been shown to improve
the stability, bioavailability, and photodynamic efficiency of organic
photosensitizer molecules. They have also been shown to behave as electron sinks
for enhanced visible-light photodynamic activities. Owing to its intrinsic near
infrared absorption properties, GO can be designed to combine both photodynamic
and photothermal hyperthermia for optimum therapeutic efficiency. Critical issues
and future aspects of photodynamic therapy research are addressed in this review.
PMID- 25848264
TI - Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for
improved therapeutic effects in cervical cancer cells.
AB - Genistein is one of the most studied isoflavonoids with potential antitumor
efficacy, but its poor water solubility limits its clinical application.
Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs
have promising applications to improve the water solubility of hydrophobic drugs.
In this work, TPGS-b-PCL copolymer was synthesized from epsilon-caprolactone
initiated by d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) through
ring-opening polymerization and characterized by Fourier transform infrared
spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation
chromatography, and thermogravimetric analysis. The genistein-loaded NPs were
prepared by a modified nanoprecipitation method and characterized in the aspects
of particle size, surface charge, morphology, drug loading and encapsulation
efficiency, in vitro drug release, and physical state of the entrapped drug. The
TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs.
MTT and colony formation experiments indicated that genistein-loaded TPGS-b-PCL
NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition
compared with pristine genistein and genistein-loaded PCL NPs. Furthermore,
compared with pristine genistein and genistein-loaded PCL NPs, the genistein
loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor
growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In
conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL
nanoparticles could enhance the anticancer effect of genistein both in vitro and
in vivo, and may serve as a potential candidate in treating cervical cancer.
PMID- 25848265
TI - Quantitative analysis of total beta-subunit of human chorionic gonadotropin
concentration in urine by immunomagnetic reduction to assist in the diagnosis of
ectopic pregnancy.
AB - BACKGROUND: The initial diagnosis of ectopic pregnancy depends on physical
examination, ultrasound, and serial measurements of total beta-subunit of human
chorionic gonadotropin (hCGbeta) concentrations in serum. The aim of this study
was to explore the possibility of using quantitative analysis of total hCGbeta in
urine rather than in serum by immunomagnetic reduction (IMR) assay as an
alternative method to diagnose an ectopic pregnancy. METHODS: We established a
standard calibration curve of IMR intensity against total hCGbeta concentration
based on standard hCGbeta samples, and used an IMR assay to detect total hCGbeta
concentrations in the urine of pregnant women with lower abdominal pain and/or
vaginal bleeding. The final diagnosis of ectopic pregnancy was based on
ultrasound scans, operative findings, and pathology reports. In this prospective
study, ten clinical samples were used to analyze the relationship of total
hCGbeta IMR signals between urine and serum. Furthermore, 20 clinical samples
were used to analyze the relationship between urine IMR signals and serum levels
of total hCGbeta. RESULTS: The calibration curve extended from 0.01 ng/mL to
10,000 ng/mL with an excellent correlation (R(2)=0.999). In addition, an
excellent correlation of total hCGbeta IMR signals between urine and serum was
noted (R(2)=0.994). Furthermore, a high correlation between urine IMR signals and
serum levels of total hCGbeta was noted (R(2)=0.862). CONCLUSION: An IMR assay
can quantitatively analyze total hCGbeta concentrations in urine, and is a
potential candidate for point-of-care testing to assist in the diagnosis of
ectopic pregnancy.
PMID- 25848266
TI - Bypassing the EPR effect with a nanomedicine harboring a sustained-release
function allows better tumor control.
AB - The current enhanced permeability and retention (EPR)-based approved
nanomedicines have had little impact in terms of prolongation of overall survival
in patients with cancer. For example, the two Phase III trials comparing
Doxil((r)), the first nanomedicine approved by the US Food and Drug
Administration, with free doxorubicin did not find an actual translation of the
EPR effect into a statistically significant increase in overall survival but did
show less cardiotoxicity. In the current work, we used a two-factor factorial
experimental design with intraperitoneal versus intravenous delivery and
nanomedicine versus free drug as factors to test our hypothesis that regional
(intraperitoneal) delivery of nanomedicine may better increase survival when
compared with systemic delivery. In this study, we demonstrate that bypassing,
rather than exploiting, the EPR effect via intraperitoneal delivery of
nanomedicine harboring a sustained-release function demonstrates dual
pharmacokinetic advantages, producing more efficient tumor control and
suppressing the expression of stemness markers, epithelial-mesenchymal
transition, angiogenesis signals, and multidrug resistance in the tumor
microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic
system) are also better controlled by intraperitoneal delivery of nanomedicine
than by standard systemic delivery of the corresponding free drug. Moreover, the
intraperitoneal delivery of nanomedicine has the potential to replace
hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and
lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the
best approach for developing a nanomedicine. Because intraperitoneal chemotherapy
is a type of regional chemotherapy, the pharmaceutical industry might consider
the regional delivery of nanomedicine as a valid alternative pathway to develop
their nanomedicine(s) with the goal of better tumor control in the future.
PMID- 25848267
TI - Research highlights from the International Journal of Nanomedicine 2014.
PMID- 25848268
TI - GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous
targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of
pancreatic cancer cells.
AB - BACKGROUND: Targeted delivery is a promising strategy to improve the diagnostic
imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)
conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225
GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct
simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted
thermochemotherapy against pancreatic cancer cells. METHODS: Fe3O4 nanoparticles
(NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then
C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean
particle size, GEM encapsulation ratio, specific cell-binding ability, and
thermal dynamic profiles were characterized. The effects of discriminating
different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and
monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the
antitumor efficiency of double/C225/magnetic-targeted and nontargeted
thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2
thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM)
assay. RESULTS: When treated with targeted nanospheres, AsPC-1 cells showed a
significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells
had similar signal strength when incubated with nontargeted nanospheres. T2
signal intensity was significantly lower when magnetic and C225 targeting were
combined, rather than used alone. The inhibitory and apoptotic rates of each
thermochemotherapy group were significantly higher than those of the chemotherapy
alone groups. Additionally, both MTT and FCM analysis verified that double
targeted thermochemotherapy had the highest targeted killing efficiency among all
groups. CONCLUSION: The C225-GEM/MANs can distinguish various EGFR-expressing
live pancreatic cancer cells, monitor diverse cellular targeting effects using
targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy
against pancreatic cancer cells.
PMID- 25848269
TI - Elucidating the in vivo fate of nanocrystals using a physiologically based
pharmacokinetic model: a case study with the anticancer agent SNX-2112.
AB - INTRODUCTION: SNX-2112 is a promising anticancer agent but has poor solubility in
both water and oil. In the study reported here, we aimed to develop a nanocrystal
formulation for SNX-2112 and to determine the pharmacokinetic behaviors of the
prepared nanocrystals. METHODS: Nanocrystals of SNX-2112 were prepared using the
wet-media milling technique and characterized by particle size, differential
scanning calorimetry, drug release, etc. Physiologically based pharmacokinetic
(PBPK) modeling was undertaken to evaluate the drug's disposition in rats
following administration of drug cosolvent or nanocrystals. RESULTS: The
optimized SNX-2112 nanocrystals (with poloxamer 188 as the stabilizer) were 203
nm in size with a zeta potential of -11.6 mV. In addition, the nanocrystals
showed a comparable release profile to the control (drug cosolvent). Further, the
rat PBPK model incorporating the parameters of particulate uptake (into the liver
and spleen) and of in vivo drug release was well fitted to the experimental data
following administration of the drug nanocrystals. The results reveal that the
nanocrystals rapidly released drug molecules in vivo, accounting for their
cosolvent-like pharmacokinetic behaviors. Due to particulate uptake, drug
accumulation in the liver and spleen was significant at the initial time points
(within 1 hour). CONCLUSION: The nanocrystals should be a good choice for the
systemic delivery of the poorly soluble drug SNX-2112. Also, our study
contributes to an improved understanding of the in vivo fate of nanocrystals.
PMID- 25848270
TI - Poly(lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for
targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells.
AB - BACKGROUND: Cancer stem cells (CSCs) possess the characteristics associated with
normal stem cells and are responsible for cancer initiation, recurrence, and
metastasis. CD133 is regarded as a CSCs marker of osteosarcoma, which is the most
common primary bone malignancy in childhood and adolescence. Salinomycin, a
polyether ionophore antibiotic, has been shown to kill various CSCs, including
osteosarcoma CSCs. However, salinomycin displayed poor aqueous solubility that
hinders its clinical application. The objective of this study was to develop
salinomycin-loaded nanoparticles to eliminate CD133(+) osteosarcoma CSCs.
METHODS: The salinomycin-loaded PEGylated poly(lactic-co-glycolic acid)
nanoparticles (SAL-NP) conjugated with CD133 aptamers (Ap-SAL-NP) were developed
by an emulsion/solvent evaporation method, and the targeting and cytotoxicity of
Ap-SAL-NP to CD133(+) osteosarcoma CSCs were evaluated. RESULTS: The
nanoparticles are of desired particle size (~150 nm), drug encapsulation
efficiency (~50%), and drug release profile. After 48 hours treatment of the Saos
2 CD133(+) osteosarcoma cells with drugs formulated in Ap-SAL-NP, SAL-NP, and
salinomycin, the concentrations needed to kill 50% of the incubated cells were
found to be 2.18, 10.72, and 5.07 MUg/mL, respectively, suggesting that Ap-SAL-NP
could be 4.92 or 2.33 fold more effective than SAL-NP or salinomycin,
respectively. In contrast, Ap-SAL-NP was as effective as SAL-NP, and less
effective than salinomycin in Saos-2 CD133(-) cells, suggesting that Ap-SAL-NP
possess specific cytotoxicity toward Saos-2 CD133(+) cells. Ap-SAL-NP showed the
best therapeutic effect in Saos-2 osteosarcoma xenograft mice, compared with SAL
NP or salinomycin. Significantly, Ap-SAL-NP could selectively kill CD133(+)
osteosarcoma CSCs both in vitro and in vivo, as reflected by the tumorsphere
formation and proportion of Saos-2 CD133(+) cells. CONCLUSION: Our results
suggest that CD133 is a potential target for drug delivery to osteosarcoma CSCs
and that it is possible to significantly inhibit the osteosarcoma growth by
killing CD133(+) osteosarcoma CSCs. We demonstrated that Ap-SAL-NP have the
potential to target and kill CD133(+) osteosarcoma CSCs.
PMID- 25848271
TI - Angiogenesis and bone regeneration of porous nano-hydroxyapatite/coralline blocks
coated with rhVEGF165 in critical-size alveolar bone defects in vivo.
AB - To improve the regenerative performance of nano-hydroxyapatite/coralline
(nHA/coral) block grafting in a canine mandibular critical-size defect model,
nHA/coral blocks were coated with recombinant human vascular endothelial growth
factor(165) (rhVEGF) via physical adsorption (3 MUg rhVEGF165 per nHA/coral
block). After the nHA/coral blocks and VEGF/nHA/coral blocks were randomly
implanted into the mandibular box-shaped defects in a split-mouth design, the
healing process was evaluated by histological observation and histomorphometric
and immunohistological analyses. The histological evaluations revealed the
ingrowth of newly formed blood vessels and bone at the periphery and cores of the
blocks in both groups at both 3 and 8 weeks postsurgery, respectively. In the
histomorphometric analysis, the VEGF/nHA/coral group exhibited a larger quantity
of new bone formation at 3 and 8 weeks postsurgery. The percentages of newly
formed bone within the entire blocks in the VEGF/nHA/coral group were 27.3% +/-
8.1% and 39.3% +/- 12.8% at 3 weeks and 8 weeks, respectively, and these values
were slightly greater than those of the nHA/coral group (21.7% +/- 3.0% and 32.6%
+/- 10.3%, respectively), but the differences were not significant (P>0.05). The
immunohistological evaluations revealed that the neovascular density in the
VEGF/nHA/coral group (146 +/- 32.9 vessel/mm(2)) was much greater than that in
the nHA/coral group (105 +/- 51.8 vessel/mm(2)) at the 3-week time point
(P<0.05), but no significant difference was observed at the 8-week time point
(341 +/- 86.1 and 269 +/- 50.7 vessel/mm(2), respectively, P>0.05). The present
study indicated that nHA/coral blocks might be optimal scaffolds for block
grafting in critical-size mandibular defects and that additional VEGF coating via
physical adsorption can promote angiogenesis in the early stage of bone healing,
which suggests that prevascularized nHA/coral blocks have significant potential
as a bioactive material for bone regeneration in large-scale alveolar defects.
PMID- 25848272
TI - Biosynthesis, characterization, and antimicrobial applications of silver
nanoparticles.
AB - In the present study, the strain Brevibacterium frigoritolerans DC2 was explored
for the efficient and extracellular synthesis of silver nanoparticles. These
biosynthesized silver nanoparticles were characterized by ultraviolet-visible
spectrophotometry, which detected the formation of silver nanoparticles in the
reaction mixture and showed a maximum absorbance at 420 nm. In addition, field
emission transmission electron microscopy revealed the spherical shape of the
nanoparticles. The dynamic light scattering results indicated the average
particle size of the product was 97 nm with a 0.191 polydispersity index.
Furthermore, the product was analyzed by energy dispersive X-ray spectroscopy, X
ray diffraction, and elemental mapping, which displayed the presence of elemental
silver in the product. Moreover, on a medical platform, the product was checked
against pathogenic microorganisms including Vibrio parahaemolyticus, Salmonella
enterica, Bacillus anthracis, Bacillus cereus, Escherichia coli, and Candida
albicans. The nanoparticles demonstrated antimicrobial activity against all of
these pathogenic microorganisms. Additionally, the silver nanoparticles were
evaluated for their combined effects with the commercial antibiotics lincomycin,
oleandomycin, vancomycin, novobiocin, penicillin G, and rifampicin against these
pathogenic microorganisms. These results indicated that the combination of
antibiotics with biosynthesized silver nanoparticles enhanced the antimicrobial
effects of antibiotics. Therefore, the current study is a demonstration of an
efficient biological synthesis of silver nanoparticles by B. frigoritolerans DC2
and its effect on the enhancement of the antimicrobial efficacy of well-known
commercial antibiotics.
PMID- 25848273
TI - Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA
vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy.
AB - Therapeutic antiangiogenesis strategies have demonstrated significant antitumor
efficacy in ovarian cancer. Recently, RNA interference (RNAi) has come to be
regarded as a promising technology for treatment of disease, especially cancer.
In this study, vascular endothelial growth factor (VEGF)-small interfering RNA
(siRNA) was encapsulated into a magnetic mesoporous silica nanoparticle (M-MSN)
based, polyethylenimine (PEI)-capped, polyethylene glycol (PEG)-grafted,
fusogenic peptide (KALA)-functionalized siRNA delivery system, termed M-MSN_VEGF
siRNA@PEI-PEG-KALA, which showed significant effectiveness with regard to VEGF
gene silencing in vitro and in vivo. The prepared siRNA delivery system readily
exhibited cellular internalization and ease of endosomal escape, resulting in
excellent RNAi efficacy without associated cytotoxicity in SKOV3 cells. In in
vivo experiments, notable retardation of tumor growth was observed in orthotopic
ovarian tumor-bearing mice, which was attributed to significant inhibition of
angiogenesis by systemic administration of this nanocarrier. No obvious toxic
drug responses were detected in major organs. Further, the magnetic core of M
MSN_VEGF siRNA@PEI-PEG-KALA proved capable of probing the site and size of the
ovarian cancer in mice on magnetic resonance imaging. Collectively, the results
demonstrate that an M-MSN-based delivery system has potential to serve as a
carrier of siRNA therapeutics in ovarian cancer.
PMID- 25848274
TI - Decisional impairments in cocaine addiction, reward bias, and cortical
oscillation "unbalance".
AB - A vast amount of research has suggested that subjects with substance use disorder
(SUD) might have difficulty making advantageous decisions that opt in favor of a
longer-term, larger reward than an immediate, smaller reward. The current
research explored the impact of reward bias and cortical frontal asymmetry (left
lateralization effect) in SUD in response to a decisional task (Iowa Gambling
Task). Fifty SUD participants and 40 controls (CG) were tested using the Iowa
Gambling Task. Electrophysiology (electroencephalography) recording was performed
during task execution. We measured left and right dorsolateral prefrontal cortex
power activity. Behavioral responses (gain/loss options); frequency band
modulation (asymmetry index) for delta, theta, alpha, and beta band; and cortical
source localization (standardized low-resolution brain electromagnetic
tomography) were considered. The SUD group opted in favor of the immediate reward
option (loss) more frequently than the long-term option (gain) when compared to
the CG. Secondly, SUD showed increased left-hemisphere activation in response to
losing (with immediate reward) choices in comparison with the CG. The left
hemispheric unbalance effect and the "reward bias" were adduced to explain the
decisional impairment in SUD.
PMID- 25848275
TI - Predictors of premature discontinuation of outpatient treatment after discharge
of patients with posttraumatic stress disorder.
AB - OBJECTIVE: This study aimed to examine the sociodemographic and disease-related
variables associated with the premature discontinuation of psychiatric outpatient
treatment after discharge among patients with noncombat-related posttraumatic
stress disorder. METHODS: We retrospectively reviewed the medical records of
patients who were discharged with a diagnosis of posttraumatic stress disorder.
RESULTS: Fifty-five percent of subjects (57/104) prematurely discontinued
outpatient treatment within 6 months of discharge. Comparing sociodemographic
variables between the 6-month non-follow-up group and 6-month follow-up group,
there were no variables that differed between the two groups. However, comparing
disease-related variables, the 6-month follow-up group showed a longer
hospitalization duration and higher Global Assessment of Function score at
discharge. The logistic regression analysis showed that a shorter duration of
hospitalization predicted premature discontinuation of outpatient treatment
within 6 months of discharge. CONCLUSION: The duration of psychiatric
hospitalization for posttraumatic stress disorder appeared to influence the
premature discontinuation of outpatient treatment after discharge.
PMID- 25848276
TI - Forehead carbuncle with intractable headache.
AB - Although carbuncles are commonly seen and may heal on their own or respond well
to treatment, in rare conditions, bacteria from carbuncles can spread into the
bloodstream and migrate to other areas of the body. Herein, we report on an
elderly female who suffered from forehead carbuncle with intractable headache,
later confirmed as having subgaleal abscess. Physicians should pay special
attention to elderly and immune-compromised patients with carbuncles located on
the middle of the face, especially when accompanied by intractable headache, to
avoid poor outcome.
PMID- 25848277
TI - Prevalence and correlates of attention-deficit hyperactivity disorder symptoms in
Korean college students.
AB - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) persists into
adulthood in a high proportion of cases, causing social difficulties and
affective problems. We evaluated the prevalence of symptoms of ADHD and the
correlates thereof in Korean college students. METHODS: A total of 2,172 college
students, stratified to reflect geographical differences, were asked to complete
self-report questionnaires on ADHD symptoms, depression, and related factors.
RESULTS: ADHD symptoms were found in 7.6% of college students. Univariate
analysis revealed that younger students had higher rates of ADHD symptoms than
did older students. We found significant associations between ADHD symptoms and
problematic alcohol use, depression, and lifetime suicidal behavior. Multivariate
analysis revealed that ADHD symptoms in adults were significantly associated with
depression (odds ratio [OR] =4.69; 95% confidence interval [CI] 3.23-6.80;
P<0.001) and overweight or obesity (OR =1.50; 95% CI 1.02-2.22; P=0.040), after
controlling for sex and age. CONCLUSION: These results have implications in terms
of the mental health interventions required to assess problems such as
depression, alcohol use, obesity, and suicidality in young adults with ADHD
symptoms.
PMID- 25848278
TI - Physical activity as a protective factor against depressive symptoms in older
Chinese veterans in the community: result from a national cross-sectional study.
AB - BACKGROUND: Physical activity is generally considered to be effective in reducing
the prevalence of depression and promoting remission of its symptoms. However,
large-scale epidemiological research on this issue is lacking in older Chinese
adults. We performed a nationwide epidemiological survey to determine the
relationship between physical activity and depressive symptoms in older Chinese
veterans in the community, with adjustment for potential confounders. METHODS: A
cross-sectional study was conducted in a representative sample of 9,676 community
dwelling older Chinese veterans. Depressive symptoms were identified using the
Center for Epidemiological Studies Depression Scale. Physical activity was self
reported using a one-year physical activity questionnaire. Information about
covariates was obtained by questionnaire-based interview. Relationships between
study variables and symptoms of depression were estimated using unadjusted and
adjusted analyses. RESULTS: The median age was 82.29 (interquartile range 80.25
84.60) years. In total, 81.84% of the study participants engaged in physical
activity that was predominantly light in intensity. In unadjusted analyses,
physical activity was associated with a significantly decreased likelihood of
depressive symptoms (5.43% versus 18.83%, P<0.0001). Multivariate logistic
regression with adjustment and controlling for confounders, physical activity was
still inversely associated with depressive symptoms and was the only independent
protective factor (odds ratio 0.57, 95% confidence interval 0.44-0.72, P<0.0001)
among the associated factors in this study. In a univariate general linear model,
there was a significant difference in Center for Epidemiological Studies
Depression Scale score between subjects participating in active physical activity
and those who did not (F=59.07, P<0.0001). CONCLUSION: This study found an
inverse relationship between physical activity and symptoms of depression in
older Chinese veterans in the community. It was also indicated that the
antidepressant effect of physical activity probably extended to the oldest-old,
and the light-intensity physical activity was probably available for the same
protective effect. This information could be used to devise further interventions
to prevent or ameliorate symptoms of depression.
PMID- 25848279
TI - Neurofibromatosis type 1 and attention deficit hyperactivity disorder: a case
study and literature review.
AB - BACKGROUND: The cognitive profile of children with neurofibromatosis type 1 (NF1)
and attention deficit hyperactivity disorder (ADHD) has been well characterized,
but few studies have evaluated the cognitive abilities of adults with NF1 and
ADHD. OBJECTIVES: We investigated 1) the cognitive profile of an adult patient
with NF1 and inattention problems, 2) changes in his cognition after 14 months of
follow-up, and 3) whether the patient exhibited comorbid NF1 and ADHD or
secondary ADHD-like symptoms. METHODS: We administered neuropsychological tests
of executive function, attention, verbal and visual memory, visuospatial
function, and language during two evaluations separated by 14 months. RESULTS: We
found no changes in sustained attention, language, or verbal memory. Visual
memory, verbal learning, selective attention inhibitory control, and problem
solving declined over time, whereas visual search, psychomotor speed,
visuospatial function, and mental flexibility improved. CONCLUSION: Our patient
exhibited a cognitive profile characteristic of both NF1 and ADHD, leading to the
hypothesis that the patient had comorbid ADHD instead of secondary ADHD-like
symptoms. More studies are necessary to characterize the cognition of patients
with NF1 and ADHD.
PMID- 25848280
TI - Association of metabotropic glutamate receptor 3 gene polymorphisms with
schizophrenia risk: evidence from a meta-analysis.
AB - To date, the role of metabotropic glutamate receptor 3 (GRM3) rs274622,
rs1468412, rs917071, rs6465084, and rs2299225 polymorphisms in schizophrenia
remains controversial. To provide a clearer picture for the effect of the five
most studied GRM3 polymorphisms on risk of schizophrenia, this meta-analysis with
eligible data from published studies was performed. Relevant case-control studies
were retrieved by literature search and selected according to established
inclusion criteria. Odds ratios with 95% confidence intervals were used to assess
the strength of association. A total of 33 individual studies were identified and
included in our meta-analysis: nine for rs1468412, with 5,314 cases and 6,147
controls; six for rs917071, with 2,660 cases and 3,517 controls; seven for
rs274622, with 3,820 cases and 4,015 controls; five for rs2299225, with 3,492
cases and 3,735 controls; and six for rs6465084, with 4,960 cases and 5,613
controls. However, no significant association was found between these GRM3
polymorphisms and schizophrenia in the overall population. With respect to
rs1468412 polymorphism, a finding of very borderline statistical significance
emerged in dominant comparison model for non-Asian populations, calling for large
scale verification to assess the marginally elevated risk of schizophrenia. In
conclusion, these GRM3 polymorphisms have limited effect on the risks of
schizophrenia. Further large and well-designed studies are needed to confirm this
conclusion.
PMID- 25848281
TI - Effects of prolonged head-down bed rest on working memory.
AB - BACKGROUND: The weightlessness caused by prolonged bed rest results in changes in
cerebral circulation and thus, brain functions, which is of interest. METHODS: We
investigated the effects of 45-day, -6 degrees head-down bed rest, which
stimulated microgravity, on working memory in 16 healthy male participants. The 2
back task was used to test the working memory variations on the 2nd day before
bed rest (R-2); on the 11th (R11), 20th (R20), 32nd (R32), and 40th (R40) days of
bed rest; and on the eighth day after bed rest (R+8). The cognitive response and
the physiological reactivity (such as galvanic skin response, heart rate, and
heart rate variability) under the 2-back task were recorded simultaneously.
RESULTS: The results showed that compared with R-2, on the R+8, the participants'
galvanic skin response increased significantly, and the high frequency of heart
rate variability (HF), low frequency of heart rate variability (LF), and reaction
time in the 2-back task decreased significantly. There were positive correlations
between the participants' reaction time of working memory and the LF/HF under
head-down bed rest (at R11, R20, and R32). CONCLUSION: The results suggested that
the prolonged head-down bed rest may have a detrimental effect on individual
physiology and working memory. Physiology indices, such as galvanic skin response
and heart rate variability, were sensitive to the prolonged bed rest.
PMID- 25848282
TI - Different presence of Chlamydia pneumoniae, herpes simplex virus type 1, human
herpes virus 6, and Toxoplasma gondii in schizophrenia: meta-analysis and
analytical study.
AB - In the present study we have performed both a meta-analysis and an analytical
study exploring the presence of Chlamydia pneumoniae, herpes simplex virus type
1, human herpes virus 6, and Toxoplasma gondii antibodies in a sample of 143
schizophrenic patients and 143 control subjects. The meta-analysis was performed
on papers published up to April 2014. The presence of serum immunoglobulin G and
immunoglobulin A was performed by enzyme-linked immunosorbent assay test. The
detection of microbial DNA in total peripheral blood was performed by nested
polymerase chain reaction. The meta-analysis showed that: 1) C. pneumoniae DNA in
blood and brain are more common in schizophrenic patients; 2) there is
association with parasitism by T. gondii, despite the existence of publication
bias; and 3) herpes viruses were not more common in schizophrenic patients. In
our sample only anti-Toxoplasma immunoglobulin G was more prevalent and may be a
risk factor related to schizophrenia, with potential value for prevention.
PMID- 25848284
TI - Erratum: Effects of switching from olanzapine to aripiprazole on the metabolic
profiles of patients with schizophrenia and metabolic syndrome: a double-blind,
randomized, open-label study [Corrigendum].
AB - [This corrects the article on p. 685 in vol. 11, PMID: 25792838.].
PMID- 25848283
TI - Patients with schizophrenia or schizoaffective disorder who receive multiple
electroconvulsive therapy sessions: characteristics, indications, and results.
AB - BACKGROUND: While electroconvulsive therapy (ECT) has been used for many years,
there is insufficient research regarding the indications for
continuation/maintenance (C/M)-ECT, its safety and efficacy, and the
characteristics of patients with schizophrenia or schizoaffective disorder who
receive multiple ECT sessions. The aims of this study were to characterize a
series of patients who received 30 ECT sessions or more, to describe treatment
regimens in actual practice, and to examine the results of C/M-ECT in terms of
safety and efficacy, especially the effect on aggression and functioning.
METHODS: We performed a retrospective chart review of 20 consecutive patients
(mean age 64.6 years) with schizophrenia (n=16) or schizoaffective disorder (n=4)
who received at least 30 ECT sessions at our ECT unit, and also interviewed the
treating physician and filled out the Clinical Global Impression-Severity, Global
Assessment of Functioning, and the Staff Observation Aggression Scale-Revised.
RESULTS: Patients received a mean of 91.3 ECT sessions at a mean interval of 2.6
weeks. All had been hospitalized for most or all of the previous 3 years. There
were no major adverse effects, and cognitive side effects were relatively minimal
(cognitive deficit present for several hours after treatment). We found that ECT
significantly reduced scores on the Staff Observation Aggression Scale-Revised
subscales for verbal aggression and self-harm, and improved Global Assessment of
Functioning scores. There were reductions in total aggression scores, subscale
scores for harm to objects and to others, and Clinical Global Impression-Severity
scores, these were not statistically significant. CONCLUSION: C/M-ECT is safe and
effective for chronically hospitalized patients. It improves general functioning
and reduces verbal aggression and self-harm. More research using other aggression
tools is needed to determine its effects and to reproduce our findings in
prospective and controlled studies.
PMID- 25848285
TI - Decreased serum levels of brain-derived neurotrophic factor in schizophrenic
patients with deficit syndrome.
AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a well-established
neurotrophin that plays a role in the pathophysiology of numerous psychiatric
disorders. Many studies have investigated the serum BDNF levels in patients with
schizophrenia. However, there are restricted data in the literature that compare
the serum BDNF levels in patients with deficit and nondeficit syndromes. In this
study, we aimed to compare the serum BDNF levels between schizophrenic patients
with deficit or nondeficit syndrome and healthy controls. METHODS: After
fulfilling the inclusion and exclusion criteria, 58 patients with schizophrenia
and 36 healthy controls were included in the study. The patients were grouped as
deficit syndrome (N=23) and nondeficit syndrome (N=35) according to the Schedule
for the Deficit Syndrome. Three groups were compared in terms of the
sociodemographic and clinical variants and serum BDNF levels. RESULTS: The groups
were similar in terms of age, sex, body mass index, and smoking status. The serum
BDNF levels in patients with deficit syndrome were significantly lower than those
in healthy controls. In contrast, the serum BDNF levels in patients with
nondeficit syndrome were similar to those in healthy controls. CONCLUSION: This
study suggests that decreased BDNF levels may play a role in the pathophysiology
of schizophrenic patients with deficit syndrome. Nonetheless, additional studies
using a larger patient sample size are needed to investigate the serum BDNF
levels in schizophrenic patients with deficit syndrome.
PMID- 25848286
TI - Aripiprazole-associated tic in a schizophrenia patient.
AB - Tic disorder, characterized by the presence of both motor and vocal tics is
common in adolescents and adults. Antipsychotics including typical antipsychotics
and atypical antipsychotics are generally recognized by experts as the most
effective pharmacological treatment for tics. However, previous studies suggest
that tic-like symptoms might manifest during treatment with atypical
antipsychotics such as clozapine, quetiapine, but not aripiprazole. We present
the first case, to our knowledge, of an adult schizophrenia patient who developed
tics during treatment with aripiprazole.
PMID- 25848288
TI - High prevalence of sleep and mood disorders in dry eye patients: survey of 1,000
eye clinic visitors.
AB - PURPOSE: We aimed to explore the prevalence of probable sleep and mood disorders
in eye clinic visitors. METHODS: This was a cross-sectional study. The
participants were outpatients at six eye clinics from January through March,
2014. Outpatients were invited to complete a questionnaire containing the
Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale
(HADS). A final diagnosis was made, and patients were classified into six
diagnostic groups. The main outcome measures were the scores of the PSQI and HADS
among the diagnostic groups. RESULTS: A total 1,000 outpatients participated, and
730 patients (mean age 59.5+/-19.0 years; 487 females) were analyzed after
exclusion of children and patients diagnosed with healthy eyes, acute injury, or
unilateral pseudophakia. The mean PSQI and HADS scores across all patients were
5.3+/-3.1 and 9.2+/-6.2, respectively. For the diagnostic groups, the mean PSQI
and HADS scores, respectively, were 5.7+/-3.3 and 10.2+/-6.0 for dry eye (n=247),
5.4+/-3.2 and 9.2+/-5.7 for bilateral cataracts (n=159), 5.3+/-3.3 and 8.0+/-5.3
for bilateral pseudophakia (n=99), and, 5.0+/-3.1 and 9.8+/-6.6 for glaucoma
(n=109). Overall, 37.3% of patients were poor sleepers (PSQI >=6), and 45.5% had
possible mood disorders (HADS >=10). Stepwise regression analysis revealed that
the PSQI and HADS scores were significantly correlated with both age (P<0.05) and
the presence of dry eye (P<0.05). CONCLUSION: The prevalence of sleep and mood
disorders was significantly higher in patients with dry eye. The present results
suggest consultation-liaison psychiatry services may be beneficial among eye
disease patients.
PMID- 25848289
TI - Erratum: A cross-sectional study on perception of stigma by Chinese schizophrenia
patients [Retraction].
AB - After many attempts over an extended period we were advised by the authors that
they were unable to provide access to the underlying data. As a result we have
been unable to assuage our serious concerns about the accuracy of the statistical
analyses and Drs Pinder and Tang have decided to retract this paper.
PMID- 25848287
TI - Major depressive disorder: mechanism-based prescribing for personalized medicine.
AB - Individual patients with depression present with unique symptom clusters -
before, during, and even after treatment. The prevalence of persistent,
unresolved symptoms and their contribution to patient functioning and disease
progression emphasize the importance of finding the right treatment choice at the
onset and the utility of switching medications based on suboptimal responses. Our
primary goal as clinicians is to improve patient function and quality of life. In
fact, feelings of well-being and the return to premorbid levels of functioning
are frequently rated by patients as being more important than symptom relief.
However, functional improvements often lag behind resolution of mood, attributed
in large part to persistent and functionally impairing symptoms - namely,
fatigue, sleep/wake disturbance, and cognitive dysfunction. Thus, patient
outcomes can be optimized by deconstructing each patient's depressive profile to
its component symptoms and specifically targeting those domains that
differentially limit patient function. This article will provide an evidence
based framework within which clinicians may tailor pharmacotherapy to patient
symptomatology for improved treatment outcomes.
PMID- 25848292
TI - Ranolazine versus placebo in patients with ischemic cardiomyopathy and persistent
chest pain or dyspnea despite optimal medical and revascularization therapy:
randomized, double-blind crossover pilot study.
AB - BACKGROUND: Patients with ischemic cardiomyopathy (ICM) may continue to
experience persistent chest pain and/or dyspnea despite pharmacologic therapy and
revascularization. We hypothesized that ranolazine would reduce anginal symptoms
or dyspnea in optimally treated ICM patients. METHODS: In this randomized, double
blind, crossover-design pilot study, 28 patients with ICM (ejection fraction less
or equal 40%) were included after providing informed consent. A total of 24
patients completed both placebo and ranolazine treatments and were analyzed. All
patients were on treatment with a beta blocker, an angiotensin-converting enzyme
inhibitor (or angiotensin receptor blocker), and at least one additional
antianginal drug. After randomization, patients received up to 1,000 mg
ranolazine orally twice a day, as tolerated, versus placebo. The primary end
point was change in angina as assessed by the Seattle Angina Questionnaire (SAQ),
or in dyspnea as assessed by the Rose Dyspnea Scale (RDS). Change in the RDS and
SAQ score from baseline was compared, for ranolazine and placebo, using the
Wilcoxon signed rank test or paired t-test. RESULTS: Patients had the following
demographic and clinical variables: mean age of 71.5 years; male (82.1%); prior
coronary bypass surgery (67.9%); prior coronary percutaneous intervention
(85.7%); prior myocardial infarction (82.1%); diabetes (67.9%); and mean ejection
fraction of 33.1%. No statistical difference was seen between baseline RDS score
and that after placebo or ranolazine (n=20) (P>=0.05). There was however, an
improvement in anginal frequency (8/10 patients) (P=0.058), quality of life (8/10
patients) (P=0.048), and mean score of all components of the SAQ questionnaire
(n=10) (P=0.047) with ranolazine compared with placebo. CONCLUSION: In optimally
treated ICM patients with continued chest pain or dyspnea, ranolazine possibly
had a positive impact on quality of life, a reduction in anginal frequency, and
an overall improvement in the mean SAQ component score compared with baseline.
Ranolazine did not change the dyspnea score compared with baseline.
PMID- 25848290
TI - Epidemiology of Japanese encephalitis: past, present, and future prospects.
AB - Japanese encephalitis (JE) is one of severe viral encephalitis that affects
individuals in Asia, western Pacific countries, and northern Australia. Although
67,900 JE cases have been estimated among 24 JE epidemic countries annually, only
10,426 have been reported in 2011. With the establishment of JE surveillance and
vaccine use in some countries, the JE incidence rate has decreased; however,
serious outbreaks still occur. Understanding JE epidemics and identifying the
circulating JE virus genotypes will improve JE prevention and control. This
review summarizes the current epidemiology data in these countries.
PMID- 25848291
TI - Pharmacokinetic drug interactions with clopidogrel: updated review and risk
management in combination therapy.
AB - BACKGROUND: Coprescribing of clopidogrel and other drugs is common. Available
reviews have addressed the drug-drug interactions (DDIs) when clopidogrel is as
an object drug, or focused on combination use of clopidogrel and a special class
of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a
precipitant drug, the factors determining the degree of DDIs, and corresponding
risk management. METHODS: A literature search was performed using PubMed,
MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic
DDIs of clopidogrel and new P2Y12 receptor inhibitors. RESULTS: Clopidogrel
affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid,
sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is
anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit
juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers,
sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when
clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John's wort,
rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining
the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540
[CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C.A),
species differences, and dose strength. The DDI risk does not exhibit a class
effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the
effects of proton pump inhibitors on clopidogrel (omeprazole, esomeprazole versus
pantoprazole, rabeprazole), the effects of rifampicin on clopidogrel versus
ticagrelor and prasugrel, and the effects of calcium channel blockers on
clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel
blockers). The mechanism of the DDIs with clopidogrel involves modulating CYP
enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4), paraoxonase-1, hepatic
carboxylesterase 1, P-glycoprotein, and organic anion transporter family member
1B1. CONCLUSION: Effective and safe clopidogrel combination therapy can be
achieved by increasing the awareness of potential changes in efficacy and
toxicity, rationally selecting alternatives, tailoring drug therapy based on
genotype, checking the appropriateness of physician orders, and performing
therapeutic monitoring.
PMID- 25848293
TI - P-wave and QT dispersion in patients with conversion disorder.
AB - OBJECTIVE: The aim of this study was to investigate QT dispersion (QTd), which is
the noninvasive marker of ventricular arrhythmia and sudden cardiac death, and P
wave dispersion, which is the noninvasive marker of atrial arrhythmia, in
patients with conversion disorder (CD). PATIENTS AND METHODS: A total of 60
patients with no known organic disease who were admitted to outpatient emergency
clinic and were diagnosed with CD after psychiatric consultation were included in
this study along with 60 healthy control subjects. Beck Anxiety Inventory and
Beck Depression Scale were administered to patients and 12-lead electrocardiogram
measurements were obtained. Pd and QTd were calculated by a single blinded
cardiologist. RESULTS: There was no statistically significant difference in terms
of age, sex, education level, socioeconomic status, weight, height, and body mass
index between CD patients and controls. Beck Anxiety Inventory scores (25.2+/
10.8 and 3.8+/-3.2, respectively, P<0.001) and Beck Depression Scale scores
(11.24+/-6.15 and 6.58+/-5.69, respectively, P<0.01) were significantly higher in
CD patients. P-wave dispersion measurements did not show any significant
differences between conversion patients and control group (46+/-5.7 vs 44+/-5.5,
respectively, P=0.156). Regarding QTc and QTd, there was a statistically
significant increase in all intervals in conversion patients (416+/-10 vs 398+/
12, P<0.001, and 47+/-4.8 vs 20+/-6.1, P<0.001, respectively). CONCLUSION: A
similar relation to that in literature between QTd and anxiety and somatoform
disorders was also observed in CD patients. QTc and QTd were significantly
increased compared to the control group in patients with CD. These results
suggest a possibility of increased risk of ventricular arrhythmia resulting from
QTd in CD patients. Larger samples are needed to evaluate the clinical course and
prognosis in terms of arrhythmia risk in CD patients.
PMID- 25848294
TI - Umeclidinium bromide/vilanterol combination in the treatment of chronic
obstructive pulmonary disease: a review.
AB - Chronic obstructive pulmonary disease (COPD) is a common disease among the
elderly that could be prevented by smoking cessation. As it is characterized by
airflow limitation that is not fully reversible, bronchodilator therapy is the
first choice of treatment. Symptomatic COPD patients with or without risk for
future exacerbations have a strong indication for the permanent use of long- and
ultralong-acting beta2-agonists and/or long-acting muscarinic antagonists.
Combining bronchodilators is an effective approach, as they demonstrate synergic
action at a cellular level and have additive clinical benefits and fewer adverse
events compared with increased doses of the monocomponents. Novel fixed-dose
combinations of long-acting beta2-agonists/long-acting muscarinic antagonists in
one inhaler have been approved for clinical use by the US Food and Drug
Administration and the European Medicines Agency. This review focuses on
published clinical trials about the fixed-dose combination of
umeclidinium/vilanterol trifenatate in patients with COPD. Results from six
studies (five of them of 12 weeks' duration and one that lasted 1 year, including
more than 6,000 patients in total) showed that umeclidinium/vilanterol
trifenatate improved lung function, dyspnea, and health-related quality of life
and decreased the exacerbation rate with no serious adverse events. More
longstanding trials are needed to evaluate the effect of the drug on disease
progression and compare it directly with other fixed-dose combinations.
PMID- 25848295
TI - Regular inhaled corticosteroids in adult-onset asthma and the risk for future
cancer: a population-based cohort study with proper person-time analysis.
AB - BACKGROUND: Recent studies have shown that inhaled corticosteroids (ICS) can
exert anti-inflammatory effects for chronic airway diseases, and several
observational studies suggest that they play a role as cancer chemopreventive
agents, particularly against lung cancer. We aimed to examine whether regular ICS
use was associated with a reduced risk for future malignancy in patients with
newly diagnosed adult-onset asthma. METHODS: We used a population-based cohort
study between 2001 and 2008 with appropriate person-time analysis. Participants
were followed up until the first incident of cancer, death, or to the end of
2008. The Cox model was used to derive an adjusted hazard ratio (aHR) for cancer
development. Kaplan-Meier cancer-free survival curves of two groups were
compared. RESULTS: The exposed group of 2,117 regular ICS users and the
nonexposed group of 17,732 non-ICS users were assembled. After 7,365 (mean, 3.5
years; standard deviation 2.1) and 73,789 (mean, 4.1 years; standard deviation
2.4) person-years of follow-up for the ICS users and the comparator group of non
ICS users, respectively, the aHR for overall cancer was nonsignificantly elevated
at 1.33 with 95% confidence interval (CI), 1.00-1.76, P=0.0501. The Kaplan-Meier
curves for overall cancer-free proportions of both groups were not significant
(log-rank, P=0.065). Synergistic interaction of concurrent presence of regular
ICS use was conducted using "ICS-negative and chronic obstructive pulmonary
disease (COPD)-negative" as the reference. The aHR for the group of "ICS
positive, COPD-negative" did not reach statistically significant levels with aHR
at 1.38 (95% CI, 0.53-3.56). There was a statistically significant synergistic
interaction of concurrent presence of regular ICS use and COPD with aHR at 3.78
(95% CI, 2.10-6.81). CONCLUSION: The protective effect of regular ICS use in the
studied East Asian patients with adult-onset asthma was not detectable, contrary
to reports of previous studies that ICS might prevent the occurrence of future
cancer.
PMID- 25848296
TI - Distribution and resistance of pathogens in liver transplant recipients with
Acinetobacter baumannii infection.
AB - BACKGROUND: Drug-resistant Acinetobacter baumannii has become a major problem in
liver transplant recipients. The aim of this study was to investigate the
clinical presentation, distribution, and drug susceptibility characteristics in
liver recipients with A. baumannii infection. METHODS: We retrospectively
investigated 17 liver recipients who developed A. baumannii infection between
January 1, 2007 and December 31, 2014. The distribution of A. baumannii and drug
susceptibility characteristics were reviewed. RESULTS: Infectious complications
due to A. baumannii appeared in 17 liver recipients, with a total of 24 episodes.
Approximately 63% (15/24) of A. baumannii infections occurred within 2 weeks
after transplantation. The most common source of infection was multiple culture
positive sites (35.3%, n=6), followed by the intra-abdominal/biliary tract
(23.5%, n=4) and lung (23.5%, n=4). Eight patients (47.1%) had a body temperature
of 38 degrees C or higher at the onset of A. baumannii infection. Nine, seven,
and 12 recipients had a serum creatinine level of >1.5 mg/dL, a white blood cell
count of >15,000/mm(3), and a platelet count of <50,000/mm(3), respectively.
There were five (29.4%) cases of septic shock and eight (47.1%) deaths. The rate
of antibiotic resistance of A. baumannii to ten of 12 antibiotics investigated
was more than 60%. Among the 24 infections caused by A. baumannii, 75% were
carbapenem-resistant. The rods were relatively sensitive to tigecycline and
cefoperazone-sulbactam. CONCLUSION: The clinical manifestations of A. baumannii
infection included a high body temperature, a decreased platelet count, an
elevated white blood cell count, and onset in the early period after
transplantation as well as high mortality. The antibiotic resistance rate of A.
baumannii was extremely high. Prevention measures and combination antibiotic
therapy are needed to improve the outcomes of liver recipients with A. baumannii
infections.
PMID- 25848297
TI - Combination of tadalafil and finasteride for improving the symptoms of benign
prostatic hyperplasia: critical appraisal and patient focus.
AB - The evidence suggests that combination therapy for benign prostatic hyperplasia
(BPH)-lower urinary tract symptoms (LUTS) using an alpha-blocker and a 5alpha
reductase inhibitor has become well accepted. The combination of daily tadalafil
and an alpha-blocker has also demonstrated benefit. This paper addresses
combination therapy with daily tadalafil and finasteride for the treatment of BPH
LUTS. Our results demonstrate that use of tadalafil and finasteride represents a
logical extension of combination therapies. We analyze a landmark study by Casabe
et al that demonstrates improved voiding symptoms as assessed by International
Prostate Symptom Scores with a combination of tadalafil and finasteride compared
with finasteride and placebo. Study patients had moderate to severe LUTS and
prostate volumes >30 g. The additional benefit of improved erectile function as
assessed by International Index of Erectile Function-erectile function domain
scores with the addition of tadalafil was a secondary benefit. We propose that
the ideal patient for combination therapy with tadalafil and finasteride has a
prostate volume >30 g and desires additional benefit over monotherapy. For these
men, improved erectile function without sexual side effects was a secondary
benefit.
PMID- 25848298
TI - The unsolved case of "bone-impairing analgesics": the endocrine effects of
opioids on bone metabolism.
AB - The current literature describes the possible risks for bone fracture in chronic
analgesics users. There are three main hypotheses that could explain the
increased risk of fracture associated with central analgesics, such as opioids:
1) the increased risk of falls caused by central nervous system effects,
including sedation and dizziness; 2) reduced bone mass density caused by the
direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism.
The impact of opioids varies by sex and among the type of opioid used (less, for
example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency
is correlated with an increased risk of osteoporosis; thus, despite that
standards have not been established for monitoring and treating opioid-induced
hypogonadism or hypoadrenalism, all patients chronically taking opioids
(particularly at doses >=100 mg morphine daily) should be monitored for the early
detection of hormonal impairment and low bone mass density.
PMID- 25848299
TI - Alemtuzumab for the treatment of multiple sclerosis.
PMID- 25848300
TI - Prostanoid therapies in the management of pulmonary arterial hypertension.
AB - Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through
actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary
arterial hypertension (PAH) is characterized by elevated mean pulmonary artery
pressure due to a high pulmonary vascular resistance state. A relative decrease
in prostacyclin presence has been associated with PAH; this pathway has thus
become a therapeutic target. Epoprostenol, the synthetic equivalent of
prostacyclin, was first utilized as short-term or bridging therapy in the 1980s.
Further refinement of its long-term use via continuous intravenous infusion
followed. A randomized controlled trial by Barst et al in 1996 demonstrated
functional, hemodynamic, and mortality benefits of epoprostenol use. This work
was a groundbreaking achievement in the management of PAH and initiated a wave of
research that markedly altered the dismal prognosis previously associated with
PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit
increased stability and allow for an extended array of parenteral and non
parenteral (inhaled and oral) therapeutic options. This review further examines
the pharmacology and clinical use of epoprostenol and its analogs in PAH.
PMID- 25848301
TI - Lowering triglycerides to modify cardiovascular risk: will icosapent deliver?
AB - Despite the clinical benefits of lowering levels of low-density lipoprotein
cholesterol, many patients continue to experience cardiovascular events. This
residual risk suggests that additional risk factors require aggressive
modification to result in more effective prevention of cardiovascular disease.
Hypertriglyceridemia has presented a considerable challenge with regard to
understanding its role in the promotion of cardiovascular risk. Increasing
evidence has established a clear causal role for elevated triglyceride levels in
vascular risk. As a result, there is increasing interest in the development of
specific therapeutic strategies that directly target hypertriglyceridemia. This
has seen a resurgence in the use of omega-3 fatty acids for the therapeutic
lowering of triglyceride levels. The role of these agents and other emerging
strategies to reduce triglyceride levels in order to decrease vascular risk are
reviewed.
PMID- 25848302
TI - Experimental study of sutureless vascular anastomosis with use of glued
prosthesis in rabbits.
AB - OBJECTIVE: The objective of this study is to explore the feasibility and efficacy
of a new technique for sutureless vascular anastomosis, using glued prosthesis,
as a sole anastomosis fixation method in rabbits. METHODS: Ten rabbits were
randomly selected to conduct the experiment. Five rabbits underwent direct
anastomosis of infrarenal abdominal aorta, with glued prosthesis. In five other
rabbits, reconstruction was done by sutured anastomosis. All animals were
immediately examined by echo-Doppler for patency of anastomosis. The burst
pressure of the glued anastomosis was measured and compared with that of a
sutured artery. The animals were euthanized, and tissue samples were taken for
histological examination immediately after the experiment. RESULTS: Compared to
conventional anastomoses, sutureless vascular anastomoses required shorter time
of creation and significantly reduced blood loss (P<5%). There was no significant
difference on the average blood flow through the anastomosis between two groups
at the end of surgery. All anastomoses with glued prosthesis, examined by echo
Doppler, were patent at the anastomotic site, except one, which was stenosed
immediately after surgery. In the control group, except one with stenosis, all
conventional anastomoses were patent. Mean burst pressure at the anastomotic site
for sutureless anastomoses was lower than in control group. Macroscopically, the
BioGlue did not demonstrate any adhesion to the surrounding tissue as it was
covered by the vascular prosthesis. Histological examination showed low-grade
inflammatory reaction in glued anastomoses versus no inflammatory reaction at the
sutured anastomoses. CONCLUSION: This technique may provide a feasible and
successful alternative in vascular surgery. However, further long-term studies
are necessary to elucidate the break pressure and degree of inflammation at the
anastomotic site.
PMID- 25848303
TI - Improving patient experience in a pediatric ambulatory clinic: a mixed method
appraisal of service delivery.
AB - OBJECTIVE: In 2013, customer satisfaction surveys showed that patients were
unhappy with the services provided at our ambulatory clinic. In response, we
performed an appraisal of our services, which resulted in the development of a
strategy to reduce waiting time and improve quality of service. Infrastructural
changes to our clinic's waiting room, consultation rooms, and back offices were
performed, and schedules were redesigned to reduce wait time to 10 minutes and
increase consultation time to 20 minutes. Our objective was to identify if this
would improve 1) accessibility to caregivers and 2) quality of service and
available amenities. DESIGN: We conducted a multi-method survey using 1) a
patient flow analysis to analyze the flow of service and understand the impact of
our interventions on patient flow and 2) specially designed questionnaires to
investigate patients' perceptions of our wait time and how to improve our
services. RESULTS: The results showed that 79% of our respondents were called in
to see a doctor within 20 minutes upon arrival. More patients (55%) felt that 10
20 minutes was an acceptable wait time. We also observed a perceived increase in
satisfaction with wait time (94%). Finally, a large number of patients (97%) were
satisfied with the quality of service and with the accessibility to caregivers
(94%). CONCLUSION: The majority of our patients were satisfied with the
accessibility to our ambulatory clinics and with the quality of services
provided. The appraisal of our operational processes using a patient flow
analysis also demonstrated how this strategy could effectively be applied to
investigate and improve quality of service in patients.
PMID- 25848304
TI - Morbid obese adults increased their sense of coherence 1 year after a patient
education course: a longitudinal study.
AB - BACKGROUND: Personal factors are key elements to understand peoples' health
behavior. Studies of such factors are important to develop targeted interventions
to improve health. The main purpose of this study is to explore sense of
coherence (SOC) in a sample of persons with morbid obesity before and after
attending a patient education course and to explore the association between SOC
and sociodemographic and other personal factors. METHODS: In this longitudinal
purposely sampled study, the participants completed questionnaires on the first
day of the course and 12 months after course completion. Sixty-eight participants
had valid scores on the selected variables at follow-up: SOC, self-esteem, and
self-efficacy. Relationships were assessed with correlation analyses and paired
and independent samples t-tests and predictors with linear regression analyses.
RESULTS: From baseline to follow-up, the total SOC score and the subdimension
scores comprehensibility, manageability, and meaningfulness all increased
significantly. At both time points, the SOC scores were low compared to the
general population but similar to scores in other chronically ill. At baseline, a
multivariate analysis showed that older age, having paid work, and higher self
esteem were directly related to higher total SOC score after controlling for
other sociodemographic factors and the participants' level of self-efficacy.
Multivariate analyses of the relationship between baseline predictors of SOC at
12-month follow-up, controlling for baseline SOC scores or sociodemographic or
personal factors, revealed that none of these variables independently predicted
SOC scores at follow-up. CONCLUSION: The total SOC score and its subdimensions
increased significantly at follow-up. SOC may be a useful outcome measure for
lifestyle interventions in people with morbid obesity and possibly other health
care problems. Subdimension scores may give an indication of what is poorly
developed and needs strengthening. This might guide choices for targeted
cognitive and psychosocial interventions. Further studies are needed to explore
this issue with larger samples.
PMID- 25848305
TI - Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence
from 31 case-control studies.
AB - BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2), a critical enzyme for the
detoxification of alcohol, is associated with many types of cancers. To verify
the relationship of ALDH2 rs671 G>A polymorphism and esophageal cancer (EC), we
performed a meta-analysis of a total of 31 published data including 8,510
patients and 16,197 controls. METHODS: The pooled odds ratio (OR) and the 95%
confidence interval (CI) were calculated using a fixed or random-effects model.
Heterogeneity (PH ), publication bias, and sensitivity analysis were also
determined. RESULTS: Although a protective effort was found in the rs671
homozygote comparison (AA/GG: OR=0.69; 95% CI=0.48-0.98), the heterozygote
comparison was apparently associated with the risk of EC, particularly in the
Chinese population ( AG/GG: OR=1.39; 95% CI=1.03-1.87). Alcohol consumption
remarkably increased this risk, especially in the AG genotype. Drinking men with
the AG genotype appeared to show a higher risk ( AG/GG: OR=4.39; 95% CI=1.24
6.55) than drinking women. CONCLUSION: The present meta-analysis provided
advanced information regarding the association of the ALDH2 A>G polymorphism and
EC. Taken together, insights from this study suggested an enhanced effect on the
development of EC through a genetic-environmental interaction.
PMID- 25848306
TI - Protective effect of gonadotropin-releasing hormone analog on the ovarian reserve
in rats receiving cyclophosphamide treatment.
AB - OBJECTIVE: The aim of the study reported here was to investigate the protective
effect of gonadotropin-releasing hormone analog (GnRHa) against cyclophosphamide
(CTX)-induced gonadotoxicity. METHODS: Eighty Fischer 344 rats were divided
randomly into four groups (20 per group). One group received normal saline, one
GnRHa, one CTX, and one GnRHa+CTX. Several parameters were used to observe the
ovarian reserve, including ovary weight, follicle number and diameter,
concentrations of estradiol (E2) and follicle-stimulating hormone (FSH), and
expressions of sex hormone receptors. RESULTS: When treatment was finished, the
number of small follicles in the GnRHa+CTX group was significantly higher than in
the CTX-alone group. Thirty days after treatment, the ovary weight, percentage of
small follicles, mean follicular diameter, and serum concentrations of E2 and FSH
in the GnRHa+CTX group all recovered, approaching normal levels. Sex hormone
receptors did not show significant differences between the four groups.
CONCLUSION: Combination treatment with GnRHa could prevent CTX-induced damage to
ovarian reserve.
PMID- 25848307
TI - Postnatal oogenesis in humans: a review of recent findings.
AB - In spite of generally accepted dogma that the total number of follicles and
oocytes is established in human ovaries during the fetal period of life rather
than forming de novo in adult ovaries, some new evidence in the field challenges
this understanding. Several studies have shown that different populations of stem
cells, such as germinal stem cells and small round stem cells with diameters of 2
to 4 MUm, that resembled very small embryonic-like stem cells and expressed
several genes related to primordial germ cells, pluripotency, and germinal
lineage are present in adult human ovaries and originate in ovarian surface
epithelium. These small stem cells were pushed into the germinal direction of
development and formed primitive oocyte-like cells in vitro. Moreover, oocyte
like cells were also formed in vitro from embryonic stem cells and induced
pluripotent stem cells. This indicates that postnatal oogenesis is not excluded.
It is further supported by the occurrence of mesenchymal stem cells that can
restore the function of sterilized ovaries and lead to the formation of new
follicles and oocytes in animal models. Both oogenesis in vitro and
transplantation of stem cell-derived "oocytes" into the ovarian niche to direct
their natural maturation represent a big challenge for reproductive biomedicine
in the treatment of female infertility in the future and needs to be explored and
interpreted with caution, but it is still very important for clinical practice in
the field of reproductive medicine.
PMID- 25848308
TI - Evaluation of the appropriateness of imipenem/cilastatin prescription and dosing
in a tertiary care hospital.
AB - BACKGROUND: Imipenem/cilastatin is an antibacterial agent of the carbapenem class
of beta-lactams that is known to have an extremely wide spectrum of activity
against Gram-positive, Gram-negative, aerobic, anaerobic, and even multidrug
resistant strains. The objective of this study was to evaluate the appropriate
use of imipenem/cilastatin in a local tertiary care hospital. The study assessed
the indication both empirically and after the culture results were available, the
dose and dose adjustment in renal failure, as well as the incidence of seizure in
hospitalized patients receiving imipenem/cilastatin. METHODS: This observational
study was conducted in a tertiary care hospital over a 3-month period. The
treatment of 100 patients with imipenem/cilastatin was evaluated both empirically
and after culture results were available. Analysis of the appropriateness of
imipenem/cilastatin indication, dose, and monitoring of seizure frequency was
based on the package insert, updated published guidelines, and clinical judgment.
RESULTS: Patients from internal medicine and intensive care units comprised
approximately 50% of the population in the study. The patients received
imipenem/cilastatin mainly for urinary tract infections (27%) or for sepsis of an
unknown focus (22%). The use of imipenem/cilastatin empirically was appropriate
in 97.2% (n=69/71) of the cases, and its use postculture in 86% of the cases.
There were 29% of the patients who were not started on imipenem/cilastatin
empirically. Four patients out of the 29 patients (13.8%) who were not started on
imipenem/cilastatin empirically inappropriately received imipenem/cilastatin post
culture results. Thirty-three patients (33%) were not dosed appropriately, 30 of
whom had renal impairment and creatinine clearance fluctuations. Only one patient
developed a seizure while on imipenem/cilastatin. CONCLUSION: The prescription of
imipenem/cilastatin at our setting was mostly appropriate to what is recommended
in the guidelines and the literature, although a few cases could have been
managed better. Dosage adjustment, however, was not as appropriate, mainly in
patients who did not have a stable creatinine clearance.
PMID- 25848309
TI - Disability-adjusted life years lost due to diabetes in France, Italy, Germany,
Spain, and the United Kingdom: a burden of illness study.
AB - AIMS: To compare the burden of disease (BoD) attributable to diabetes expressed
in disability-adjusted life years (DALYs) for five European countries in 2010.
METHODS: DALYs lost to diabetes as the sum of years of life lost and years lived
with disability were estimated by sex and age using country-specific
epidemiological data and global disability weights. Data from various secondary
sources were combined to estimate health loss due to diabetes for France,
Germany, Italy, Spain, and the UK. National statistical databases were used and
if necessary, community studies were used to derive the prevalence of diabetes by
sex and age group, which were weighted proportionately for a national population
burden of disease estimate. All identified data were adapted to the Global Burden
of Disease methodology (2010) to calculate the burden attributable to diabetes.
No age weighting and discounting was applied. Sensitivity to different sources of
variation was examined. Germany and Italy lost the largest number of DALYs due to
diabetes, with 5.9 and 5.8 per 1,000 inhabitants, respectively, followed by Spain
(4.4), France (3.7), and the UK (2.9). The highest burden was caused by mortality
due to diabetes, with the exception of the UK, for which the burden due to
disability of diabetes was higher. Mean DALYs lost were higher for women in
Germany, Italy, and Spain and shown to increase with age for all countries.
Sensitivity analysis in variation in disability weights and uncertainty in
epidemiological data were shown to have effects on DALYs lost. CONCLUSION: In
spite of data limitations, the estimates reported here show that DALY loss due to
diabetes imposes a substantial burden on countries. Cross-national variation in
disease epidemiology was the largest source of variation in the burden of
diabetes between countries.
PMID- 25848310
TI - Effect of eprosartan-based antihypertensive therapy on coronary heart disease
risk assessed by Framingham methodology in Canadian patients with diabetes:
results of the POWER survey.
AB - OBJECTIVE: As part of the Physicians' Observational Work on Patient Education
According to their Vascular Risk (POWER) survey, we used Framingham methodology
to examine the effect of an eprosartan-based regimen on total coronary heart
disease (CHD) risk in diabetic patients recruited in Canada. METHODS: Patients
with new or uncontrolled hypertension (sitting systolic blood pressure [SBP] >140
mmHg with diastolic blood pressure <110 mmHg) were identified at 335 Canadian
primary care practices. Initial treatment consisted of eprosartan 600 mg/day,
which was later supplemented with other antihypertensives as required. Outcomes
included change in SBP at 6 months (primary objective) and absolute change in the
Framingham 10-year CHD risk score (secondary objective). RESULTS: We identified
an intention-to-treat diabetes population of 195 patients. Most diabetic patients
were prescribed two or more antihypertensive drugs throughout the survey. Mean
reductions in SBP and diastolic blood pressure were 20.8+/-14.8 mmHg and 9.5+/
10.7 mmHg, respectively. The overall absolute mean 10-year CHD risk, calculated
using Framingham formulae, declined by 2.9+/-3.5 points (n=49). Average baseline
risk was higher in men than women (14.8+/-8.6 versus 5.6+/-1.8 points); men also
had a larger average risk reduction (4.2+/-4.3 versus 1.5+/-1.3 points). The
extent of absolute risk reduction also increased with increasing age (trend not
statistically significant). CONCLUSION: Eprosartan-based therapy substantially
reduced arterial blood pressure in our subset of diabetic patients; while there
was a slight reduction in Framingham risk, there are indications from our data
that both blood pressure control and the wider management of CHD risk in diabetic
patients remains suboptimal in Canadian primary care.
PMID- 25848311
TI - Aggressive digital papillary adenocarcinoma - a rare malignant tumor of the sweat
glands: two case reports and a review of the literature.
AB - Aggressive digital papillary adenocarcinomas are rare malignant tumors often
located on the digits of the hand. Due to lack of pain, slow growth, and an
inconspicuous appearance, diagnosis is often missed or delayed. We report two
cases and review the present literature to give recommendations for diagnosis and
treatment.
PMID- 25848312
TI - Successful use of a topical mixture with ozolipoile in the treatment of actinic
ulcers.
AB - PURPOSE: Post-radiation skin damage is the result of alterations produced in the
irradiated zone. There are different studies aimed at verifying the effectiveness
of several kinds of molecules in the treatment of radiation-induced skin damage.
The purpose of this study is to test a mixture with a formulation containing
several natural active ingredients on actinic ulcers in patients receiving
radiation therapies. PATIENTS AND METHODS: The authors recruited 13 patients, and
randomly divided them into a test group (T1) and a control group (T2). The
patients in both groups were undergoing radiotherapy. The T1 group was treated
with a mixture called ozolipoile, whereas the T2 group was administered
hyaluronic acid gel followed by non-ablative laser therapy. We evaluated the
obtained results, the time of clinical healing, the reduction of pain, and each
side effect, comparing all data between the T1 and T2 groups. RESULTS: The
average Visual Analog Scale results showed decrease in pain in both groups;
however, while the T1 group showed a significant decrease in the values, the T2
group reported a more gradual reduction in the values, without ever reaching the
minimum values obtained with the treatment with ozolipoile. CONCLUSION: Treatment
of actinic ulcers with ozolipoile mixture leads to faster control of pain and to
better healing of small-size ulcers.
PMID- 25848313
TI - Inflammatory bowel disease and anxiety: links, risks, and challenges faced.
AB - Inflammatory bowel disease (IBD) causes severe physical symptoms and is also
associated with psychological comorbidities. Abnormal anxiety levels are found in
up to 40% of patients with IBD. Anxiety symptoms are often related to flares of
IBD but may persist in times of remission. Detection of anxiety disorder (AD) in
patients with IBD can be challenging. Patients with anxiety may also exhibit
symptoms in keeping with functional gastrointestinal disorders (FGID). Evidence
for the effectiveness of pharmacological and psychological therapies for anxiety
stems from patients without IBD. Studies in patients with IBD have either been
small or shown negative results. In light of this, a combined approach involving
IBD physicians to improve disease control and psychologists or psychiatrists to
treat anxiety is advised. This review examines the evidence of anxiety issues in
IBD with a focus on extent of the problem, risk factors for anxiety, and the
effectiveness of interventions.
PMID- 25848314
TI - Respiratory metapneumoviral infection without co-infection in association with
acute and chronic lung allograft dysfunction.
AB - BACKGROUND: Metapneumoviral respiratory infection is a community-acquired
respiratory viral (CARV) infection. Lung transplantation recipients exposed to
CARV are at risk for development of allograft rejection. The cellular and
molecular pathways initiated by viral infection leading to allograft dysfunction
are not completely understood. The aim of this study was to identify human
metapneumoviral (hMPV) cases in association with allograft rejection. METHODS: A
literature search was conducted to identify cases of both hMPV and allograft
rejection within 6 months of the initial infection. This resulted in 1,007 lung
transplantation recipients, with a total of 2,883 samples identified. Of these,
57 demonstrated isolated hMPV without co-infection with other agents. RESULTS:
The results of the study indicate that 35% of acute hMPV infections without co
infection, at the time of detection by molecular diagnostic platforms, were
associated with acute cellular rejection within 3 months. There were 9.4% of the
cases subsequently associated with chronic allograft dysfunction/bronchiolitis
obliterans syndrome, which was collectively termed chronic rejection for purposes
of analysis. In conclusion, the prompt identification of isolated hMPV from lung
transplantation patients is an important treatable risk factor for subsequent
allograft dysfunction. The cellular and molecular pathogenesis of viral-induced
allograft rejection remains a topic of future study.
PMID- 25848315
TI - The effects of grounding (earthing) on inflammation, the immune response, wound
healing, and prevention and treatment of chronic inflammatory and autoimmune
diseases.
AB - Multi-disciplinary research has revealed that electrically conductive contact of
the human body with the surface of the Earth (grounding or earthing) produces
intriguing effects on physiology and health. Such effects relate to inflammation,
immune responses, wound healing, and prevention and treatment of chronic
inflammatory and autoimmune diseases. The purpose of this report is two-fold: to
1) inform researchers about what appears to be a new perspective to the study of
inflammation, and 2) alert researchers that the length of time and degree
(resistance to ground) of grounding of experimental animals is an important but
usually overlooked factor that can influence outcomes of studies of inflammation,
wound healing, and tumorigenesis. Specifically, grounding an organism produces
measurable differences in the concentrations of white blood cells, cytokines, and
other molecules involved in the inflammatory response. We present several
hypotheses to explain observed effects, based on current research results and our
understanding of the electronic aspects of cell and tissue physiology, cell
biology, biophysics, and biochemistry. An experimental injury to muscles, known
as delayed onset muscle soreness, has been used to monitor the immune response
under grounded versus ungrounded conditions. Grounding reduces pain and alters
the numbers of circulating neutrophils and lymphocytes, and also affects various
circulating chemical factors related to inflammation.
PMID- 25848316
TI - Repository corticotropin injection in a patient presenting with focal segmental
glomerulosclerosis, rheumatoid arthritis, and optic neuritis: a case report.
AB - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) causes scarring or
sclerosis of glomeruli that act as tiny filters in the kidneys, damage to which
results in diminished ability to properly filter blood, resulting in the urinary
loss of plasma proteins and subsequent proteinuria. CASE PRESENTATION: A 60-year
old, white female with a history of intermittent proteinuria was referred by her
primary care physician for renal dysfunction. Biopsy confirmed FSGS and she was
treated with an angiotensin-converting enzyme inhibitor. She also had rheumatoid
arthritis (RA) but no active synovitis and was maintained on prednisone 5 mg/d.
She also complained of worsening vision in her right eye and was diagnosed with
optic neuritis (ON). She remained stable for about 8 months when examination
indicated FSGS relapse, and she reported painful RA flares. She was treated with
Acthar((r)) Gel (40 mg biweekly) for 6 months, after which proteinuria and urine
protein-to-creatinine ratio decreased to about half. Her ON improved, and she
reported that she had fewer RA flares and pain improved by 50%. This case of
confirmed FSGS showed an improved response to treatment with Acthar Gel for FSGS
with concomitant RA and ON. CONCLUSION: This referral case is relevant to primary
care practitioners who treat disorders that may be responsive to corticosteroid
therapy. The antiproteinuric effects and ancillary improvement in RA and ON
symptoms during treatment with Acthar Gel are not entirely explained by its
steroidogenic actions. ACTH is a bioactive peptide that, together with alpha
melanocyte-stimulating hormone, exhibits biologic efficacy by modulating
proinflammatory cytokines and subsequent leukocyte extravasation and may have
autocrine/paracrine effects in joints. While Acthar Gel was primarily
administered in this case to treat proteinuria, it also showed ancillary benefits
in patients with concomitant inflammatory disease states.
PMID- 25848317
TI - Surviving severe traumatic brain injury in Denmark: incidence and predictors of
highly specialized rehabilitation.
AB - PURPOSE: To identify all hospitalized patients surviving severe traumatic brain
injury (TBI) in Denmark and to compare these patients to TBI patients admitted to
highly specialized rehabilitation (HS-rehabilitation). PATIENTS AND METHODS:
Patients surviving severe TBI were identified from The Danish National Patient
Registry and The Danish Head Trauma Database. Overall incidence rates of
surviving severe TBI and incidence rates of admission to HS-rehabilitation after
severe TBI were estimated and compared. Patient-related predictors of no
admission to HS-rehabilitation among patients surviving severe TBI were
identified using multivariable logistic regression. RESULTS: The average
incidence rate of surviving severe TBI was 2.3 per 100,000 person years.
Incidence rates of HS-rehabilitation were generally stable around 2.0 per 100,000
person years. Overall, 84% of all patients surviving severe TBI were admitted to
HS-rehabilitation. Female sex, older age, and non-working status pre-injury were
independent predictors of no HS-rehabilitation among patients surviving severe
TBI. CONCLUSION: The incidence rate of hospitalized patients surviving severe TBI
was stable in Denmark and the majority of the patients were admitted to HS
rehabilitation. However, potential inequity in access to HS-rehabilitation may
still be present despite a health care system based on equal access for all
citizens.
PMID- 25848318
TI - Does the use of a novel self-adhesive flowable composite reduce nanoleakage?
AB - OBJECTIVE: The aim of the study reported here was to evaluate the performance of
a self-adhesive flowable composite and two self-etching adhesive systems, when
subjected to cyclic loading, in preventing the nanoleakage of Class V
restorations. METHODS: Wedge-shape Class V cavities were prepared (4*2*2 mm
[length * width * depth]) on the buccal surfaces of 90 sound human premolars.
Cavities were divided randomly into three groups (n=30) according to the used
adhesive (Xeno((r)) V [self-etching adhesive system]) and BOND-1((r)) SF (solvent
free self-etching adhesive system) in conjunction with Artiste((r)) Nano
Composite resin, and FusioTM Liquid Dentin (self-adhesive flowable composite),
consecutively. Each group was further divided into three subgroups (n=10): (A)
control, (B) subjected to occlusal cyclic loading (90N for 5,000 cycles), and (C)
subjected to occlusal cyclic loading (90N for 10,000 cycles). Teeth then were
coated with nail polish up to 1 mm from the interface, immersed in 50% silver
nitrate solution for 24 hours and tested for nanoleakage using the environmental
scanning electron microscopy and energy dispersive analysis X-ray analysis. Data
were statistically analyzed using two-way analysis of variance and Tukey's post
hoc tests (P<=0.05). RESULTS: The Fusio Liquid Dentin group showed statistically
significant lower percentages of silver penetration (0.55 MU) compared with the
BOND-1 SF (3.45 MU) and Xeno V (3.82 MU) groups, which were not statistically
different from each other, as they both showed higher silver penetration.
CONCLUSION: Under the test conditions, the self-adhesive flowable composite
provided better sealing ability. Aging of the two tested adhesive systems, as a
function of cyclic loading, increased nanoleakage.
PMID- 25848319
TI - Health care coverage among long-distance truckers in India: an evaluation based
on the Tanahashi model.
AB - Long-distance truckers (LDTDs) are vulnerable to human immunodeficiency virus
infection and other sexually transmitted infections due to the nature of their
work, working environment, and frequent mobility. This paper examines and
comments on the health care coverage provisioned under "Kavach" Project. Data
from the Integrated Behavioural and Biological Survey, National Highway gathered
from 2,066 LDTDs in Round 1 and 2,085 LDTDs in Round 2, who traveled in four
extreme road corridors travelled by LDTDs in India, were used for analysis.
Analysis reveals that service capacity in terms of socially marketed condoms per
thousand LDTDs has increased from Round 1 to Round 2 (4,430 to 6,876,
respectively). Accessibility coverage in terms of knowledge about the Khushi
clinic has significantly decreased between Rounds 1 and 2 (60.9% to 54.6%;
P<0.001). Acceptability coverage has increased between the two rounds (13.8% to
50.6%; P<0.001). Contact coverage has also increased between the rounds (12.7% to
22.3%; P<0.001). Effectiveness coverage for preventive and curative care has also
increased significantly. This paper comments on the gaps in accessibility and
acceptability of health care coverage and emphasizes the need for further studies
to assess the contextual factors that influence the effectiveness and efficiency
of interventions designed to address access barriers and to identify what
combination of interventions may generate the best possible outcome.
PMID- 25848320
TI - Comparative analysis of prevalence of intimate partner violence against women in
military and civilian communities in Abuja, Nigeria.
AB - INTRODUCTION: Intimate partner violence (IPV) occurs across the world, in various
cultures, and affects people across societies irrespective of economic status or
gender. Most data on IPV before World Health Organization multicountry study
(WHOMCS) usually came from sources other than the military. Result of this study
will contribute to the existing body of knowledge and may serve as a baseline for
future studies in military populations. This study compares the prevalence of the
different types of IPV against women in military and civilian communities in
Abuja, Nigeria. METHODS: Using a multistage sampling technique, 260 women who had
intimate male partners were selected from military and civilian communities of
Abuja. Collected data on personal characteristics and different types of IPV
experienced were analyzed to demonstrate comparison of the association between
the different forms of IPV and the respondents' sociodemographic and partner
characteristics in the two study populations using percentages and chi-square
statistics, and P-value was assumed to be significant at <=0.05. RESULTS: The
prevalence of the four major types of IPV was higher among the military
respondents than among civilians: controlling behavior, 37.1% versus 29.1%;
emotional/psychological abuse, 42.4% versus 13.4%; physical abuse, 19.7% versus
5.9%, and sexual abuse, 9.2% versus 8.8%. Significantly more respondents from the
military population (59 [45.4%]) compared to civilians (21 [19.4%]) were
prevented by their partners from seeing their friends (P=0.000). The situation is
reversed with regard to permission to seek health care for self, with civilians
reporting a significantly higher prevalence (35 [32.4%]) than did military
respondents (20 [15.4%]) (P=0.002). The military respondents were clearly at a
higher risk of experiencing all the variants of emotional violence than the
civilians (P=0.00). The commonest form of physical violence against women was
"being slapped or having something thrown at them, that could hurt", which was
markedly higher in the military (43 [33.1%]) than in the civilian population (10
[9.3%]), (P<0.05). CONCLUSION: IPV is a significant public health problem in
Abuja, and the military population is clearly at a higher risk of experiencing
all forms of IPV compared to the civilian population. The military should
encourage and finance research on effect of military operations and posttraumatic
stress disorders on family relationships with a view of developing evidence-based
treatment models for military personnel.
PMID- 25848322
TI - Contraceptive practices and pregnancy intendedness among pregnant adolescents.
AB - BACKGROUND: Adolescent pregnancy is a major health problem in many developing
countries. OBJECTIVE: To assess contraceptive practices and pregnancy
intendedness in pregnant adolescents. MATERIALS AND METHODS: This study was
prospectively conducted from September 2013 to June 2014. All consecutively
pregnant women between 15 and 19 years old attending the Antenatal Clinic at
Srinagarind Hospital and the Khon Kaen Branch of the Planned Parenthood
Association of Thailand were invited for participation. Face-to-face interviews
by trained interviewers using standardized questionnaires were carried out.
Logistic regression was used to determine an adjusted odds ratio (aOR) and 95%
confidence interval (CI) of independent predictors. RESULTS: Two hundred
participants were enrolled. Mean age was 17.2 years. One hundred and eighteen
(59.0%) were currently in school. Seventy-five (37.5%) participants had never
used any contraceptive methods. Of the 125 participants who had ever used
contraception, regular use of contraceptives was reported in only 21 participants
(16.8%). Only two participants (1.0%) had ever used an intrauterine device or
implant. Participants' age was a significant independent factor associated with
non-use of contraceptives (aOR, 6.42; 95% CI, 2.94-14.04). Of the 200
participants, 132 (66.0%) declared that the pregnancy was unintended. Significant
independent factors predicting unintended pregnancy were educational status (aOR,
6.17; 95% CI, 3.27-13.75) and participants' age (aOR, 5.76; 95% CI, 2.42-13.70).
CONCLUSION: Non-use and use of contraceptive methods with high failure rates were
major reasons leading to adolescent pregnancies. Participants' age was an
independent factor predicting non-use of contraceptives. Educational status and
age of the participants were significant factors predicting unintended pregnancy.
PMID- 25848321
TI - Vulvar cancer: epidemiology, clinical presentation, and management options.
AB - EPIDEMIOLOGY: Vulvar cancer can be classified into two groups according to
predisposing factors: the first type correlates with a HPV infection and occurs
mostly in younger patients. The second group is not HPV associated and occurs
often in elderly women without neoplastic epithelial disorders. HISTOLOGY:
Squamous cell carcinoma (SCC) is the most common malignant tumor of the vulva
(95%). CLINICAL FEATURES: Pruritus is the most common and long-lasting reported
symptom of vulvar cancer, followed by vulvar bleeding, discharge, dysuria, and
pain. THERAPY: The gold standard for even a small invasive carcinoma of the vulva
was historically radical vulvectomy with removal of the tumor with a wide margin
followed by an en bloc resection of the inguinal and often the pelvic lymph
nodes. Currently, a more individualized and less radical treatment is suggested:
a radical wide local excision is possible in the case of localized lesions (T1).
A sentinel lymph node (SLN) biopsy may be performed to reduce wound complications
and lymphedema. PROGNOSIS: The survival of patients with vulvar cancer is good
when convenient therapy is arranged quickly after initial diagnosis. Inguinal
and/or femoral node involvement is the most significant prognostic factor for
survival.
PMID- 25848323
TI - Clinical utility of ulipristal acetate for the treatment of uterine fibroids:
current evidence.
AB - Uterine myoma is the most common benign uterine tumor in women of reproductive
age and occurs in 20%-25% of the worldwide population. No currently approved
medical treatment is able to completely eliminate fibroids. Surgery, particularly
hysterectomy, predominates as the treatment strategy of choice, even though it is
associated with risks and complications and causes infertility. Until recently,
gonadotropin-releasing hormone agonists were the only available drugs for the
preoperative treatment of fibroids. However, ulipristal acetate (UPA), an oral
selective progesterone receptor modulator, was recently licensed in Europe for
the same indication. Recent studies have demonstrated the efficacy and safety of
UPA in the medical management of fibroids before surgery, with a better
tolerability profile than leuprolide acetate. Analyzing the literature, we
identified new management strategies involving UPA and surgery, considering
advantages of both medical and surgical therapy. The advent of UPA will
undoubtedly modify the surgical approach to fibroids, but the heterogeneity of
these possible indications now requires various original clinical studies to
identify the optimal indications for UPA in patients with symptomatic fibroid(s).
PMID- 25848325
TI - Pacing strategy in male elite and age group 100 km ultra-marathoners.
AB - Pacing strategy has been investigated in elite 100 km and elite 161 km (100 mile)
ultra-marathoners, but not in age group ultra-marathoners. This study
investigated changes in running speed over segments in male elite and age group
100 km ultra-marathoners with the assumption that running speed would decrease
over segments with increasing age of the athlete. Running speed during segments
in male elite and age group finishers for 5-year age groups (ie, 18-24 to 65-69
years) in the 100 km Lauf Biel in Switzerland was investigated during the 2000
2009 period. Average running speed over segment time station (TS) TS1-TS2 (56.1
km) was compared with running speed Start-TS1 (38 km) and Start-TS3 (76.7 km) and
running speed TS2-TS3 was compared with running speed Start-Finish. For the top
ten athletes in each edition, running speed decreased from 2000 to 2009 for TS1
TS2 and TS2-TS3 (P<0.0001) but not in TS3-Finish (P>0.05). During TS1-TS2,
athletes were running at 98.0%+/-2.1% of the running speed of Start-TS1. In TS2
TS3, they were running at 94.6%+/-3.4% of the running speed of TS1-TS2. In TS3
Finish, they were running at 95.5%+/-3.8% of running speed in TS2-TS3. For age
group athletes, running speed decreased in TS1-TS2 and TS2-TS3. In TS3-Finish,
running speed remained unchanged with the exception of the age group 40-44 years
for which running speed increased. Running speed showed the largest decrease in
the age group 18-24 years. To summarize, the top ten athletes in each edition
maintained their running speed in the last segment (TS3-Finish) although running
speed decreased over the first two segments (TS1-TS2 and TS2-TS3). The best
pacers were athletes in the age group 40-44 years, who were able to achieve
negative pacing in the last segment (TS3-Finish) of the race. The negative pacing
in the last segment (TS3-Finish) was likely due to environmental conditions, such
as early dawn and the flat circuit in segment TS3-Finish of the race.
PMID- 25848324
TI - To mesh or not to mesh: a review of pelvic organ reconstructive surgery.
AB - Pelvic organ prolapse (POP) is a major health issue with a lifetime risk of
undergoing at least one surgical intervention estimated at close to 10%. In the
1990s, the risk of reoperation after primary standard vaginal procedure was
estimated to be as high as 30% to 50%. In order to reduce the risk of relapse,
gynecological surgeons started to use mesh implants in pelvic organ
reconstructive surgery with the emergence of new complications. Recent studies
have nevertheless shown that the risk of POP recurrence requiring reoperation is
lower than previously estimated, being closer to 10% rather than 30%. The
development of mesh surgery - actively promoted by the marketing industry - was
tremendous during the past decade, and preceded any studies supporting its
benefit for our patients. Randomized trials comparing the use of mesh to native
tissue repair in POP surgery have now shown better anatomical but similar
functional outcomes, and meshes are associated with more complications, in
particular for transvaginal mesh implants. POP is not a life-threatening
condition, but a functional problem that impairs quality of life for women. The
old adage "primum non nocere" is particularly appropriate when dealing with this
condition which requires no treatment when asymptomatic. It is currently admitted
that a certain degree of POP is physiological with aging when situated above the
landmark of the hymen. Treatment should be individualized and the use of mesh
needs to be selective and appropriate. Mesh implants are probably an important
tool in pelvic reconstructive surgery, but the ideal implant has yet to be found.
The indications for its use still require caution and discernment. This review
explores the reasons behind the introduction of mesh augmentation in POP surgery,
and aims to clarify the risks, benefits, and the recognized indications for its
use.
PMID- 25848326
TI - Family medicine residents' perceived level of comfort in treating common sports
injuries across residency programs in the United States.
AB - BACKGROUND AND OBJECTIVE: Family physicians are expected to be comfortable in
treating common sports injuries. Evidence shows a limited level of comfort in
treating these injuries in pediatric and internal medicine residents. Studies are
lacking, however, in family medicine residents. The purpose of this study is to
assess the comfort level of family medicine residents in treating common sports
injuries in adults and children based on their perceived level of knowledge and
attitudes. METHODS: This is a cross-sectional study of family medicine residents
in the United Sates. A written survey of 25 questions related to sports injury
knowledge and factors affecting comfort level were collected. A chi-square test
was implemented in calculating P-values. RESULTS: Five hundred and fifty-seven
residents responded to the survey. A higher percentage of doctors of osteopathy
(86.6%, 82.5%, 69.6%, and 68.7%) compared to doctors of medicine (78.5%, 71.6%,
53.4%, and 52.8%) respectively identified ankle sprain, concussion, plantar
fasciitis, and lateral epicondylitis as common injuries, and felt comfortable in
treating them (P-values =0.015, 0.004, 0.0001, and 0.0002, respectively).
Residents with high interest in sports medicine correctly identified the injuries
as common and felt comfortable treating them as well (knowledge, P=0.027, 0.0029,
<0.0001, and 0.0001, respectively; comfort level, P=0.0016, <0.0001, 0.0897, and
0.0010, respectively). CONCLUSION: Medical education background, factors that
affect training, and an interest in sports medicine contribute to residents'
knowledge and comfort level in treatment of common sports injuries.
PMID- 25848327
TI - Diagnosis, treatment, and rehabilitation of stress fractures in the lower
extremity in runners.
AB - Stress fractures account for between 1% and 20% of athletic injuries, with 80% of
stress fractures in the lower extremity. Stress fractures of the lower extremity
are common injuries among individuals who participate in endurance, high load
bearing activities such as running, military and aerobic exercise and therefore
require practitioner expertise in diagnosis and management. Accurate diagnosis
for stress fractures is dependent on the anatomical area. Anatomical regions such
as the pelvis, sacrum, and metatarsals offer challenges due to difficulty
differentiating pathologies with common symptoms. Special tests and treatment
regimes, however, are similar among most stress fractures with resolution between
4 weeks to a year. The most difficult aspect of stress fracture treatment entails
mitigating internal and external risk factors. Practitioners should address
ongoing risk factors to minimize recurrence.
PMID- 25848328
TI - Finalizing a measurement framework for the burden of treatment in complex
patients with chronic conditions.
AB - PURPOSE: The workload of health care and its impact on patient functioning and
well-being is known as treatment burden. The purpose of this study was to
finalize a conceptual framework of treatment burden that will be used to inform a
new patient-reported measure of this construct. PATIENTS AND METHODS: Semi
structured interviews were conducted with 50 chronically ill patients from a
large academic medical center (n=32) and an urban safety-net hospital (n=18). We
coded themes identifying treatment burden, with the themes harmonized through
discussion between multiple coders. Four focus groups, each with five to eight
participants with chronic illness, were subsequently held to confirm the thematic
structure that emerged from the interviews. RESULTS: Most interviewed patients
(98%) were coping with multiple chronic conditions. A preliminary conceptual
framework using data from the first 32 interviews was evaluated and was modified
using narrative data from 18 additional interviews with a racially and
socioeconomically diverse sample of patients. The final framework features three
overarching themes with associated subthemes. These themes included: 1) work
patients must do to care for their health (eg, taking medications, keeping
medical appointments, monitoring health); 2) challenges/stressors that exacerbate
perceived burden (eg, financial, interpersonal, provider obstacles); and 3)
impacts of burden (eg, role limitations, mental exhaustion). All themes and
subthemes were subsequently confirmed in focus groups. CONCLUSION: The final
conceptual framework can be used as a foundation for building a patient self
report measure to systematically study treatment burden for research and
analytical purposes, as well as to promote meaningful clinic-based dialogue
between patients and providers about the challenges inherent in maintaining
complex self-management of health.
PMID- 25848329
TI - The benefit of consolidation radiotherapy to initial disease bulk in patients
with advanced Hodgkin's disease who achieved complete remission after standard
chemotherapy.
AB - BACKGROUND/PURPOSE: The aim of this study was to evaluate the role of
consolidation radiotherapy (RT) in advanced-stage Hodgkin's disease (HD) with
initial bulky sites after radiological complete remission (CR) or partial
response (PR) with positron emission tomography-negative (metabolic CR) following
standard chemotherapy (ABVD [Adriamycin, bleomycin, vinblastine, and
dacarbazine]) six to eight cycles. PATIENTS AND METHODS: Adult patients with
advanced-stage HD treated at our institute during the period 2006 to 2012 were
retrospectively evaluated. One hundred and ninety-two patients with initial bulky
disease size (>7 cm) who attained radiological CR/PR and metabolic CR were
included in the analysis. One hundred and thirteen patients who received
radiotherapy (RT) as consolidation postchemotherapy (RT group) were compared to
79 patients who did not receive RT (non-RT group). Disease-free (DFS) and overall
survival (OS) rates were estimated using the Kaplan-Meier method and were
compared according to treatment group by the log-rank tests at P <=0.05
significance level. RESULTS: The mean age of the cohort was 33 (range: 14 to 81)
years. Eighty-four patients received involved-field radiation and 29 patients
received involved-site RT. The RT group had worse prognostic factors compared to
the non-RT group. Thirteen (12%) relapses occurred in the RT group, and 19 (24%)
relapses occurred in the non-RT group. Nine patients (8%) in the RT group died,
compared to eleven patients (14%) in the non-RT group. Second malignancies were
seen in only five patients: three patients in the RT group compared to two
patients in the non-RT group. At 5 years, overall DFS was 79%+/-9% and OS was
85%+/-9%. There was significant statistical difference between the RT group and
the non-RT group regarding 5-year DFS: 86%+/-7% and 74%+/-9%, respectively (P
<=0.02). However, the 5-year OS was 90%+/-5% for the RT group and 83%+/-8% for
the non-RT group, with no statistical difference (P <=0.3). CONCLUSION: The
results of our study suggest that consolidation RT in patients with advanced
stage HD with initial bulky disease who had postchemotherapy radiologic CR or PR
with metabolic CR improved the DFS.
PMID- 25848330
TI - A case of Hodgkin's lymphoma with severely impaired liver function treated
successfully with gemcitabine followed by ABVD.
AB - Hodgkin's lymphoma (HL) originates from clonal B cells and is the most common
malignancy in the second decade of life. Liver involvement is uncommon at
presentation in patients with HL and there is a paucity of data for treatment of
patients with severely impaired liver function. We present an unusual case of HL
with severe hepatic impairment, splenomegaly and multiple chromosomal
abnormalities that was treated initially with gemcitabine and steroids. Once
liver function tests improved, six cycles of Adriamycin, bleomycin, vinblastine,
and dacarbazine were administered. The patient remains in remission at 3.5 years
of follow-up.
PMID- 25848331
TI - Students' perceptions of the academic learning environment in seven medical
sciences courses based on DREEM.
AB - OBJECTIVE: Learning environment has a significant role in determining students'
academic achievement and learning. The aim of this study is to investigate the
viewpoints of undergraduate medical sciences students on the learning environment
using the Dundee Ready Education Environment Measure (DREEM) at Rafsanjan
University of Medical Sciences (RUMS). METHODS: The descriptive cross-sectional
study was performed on 493 medical sciences students in the following majors:
nursing, midwifery, radiology, operating room nursing, laboratory sciences,
medical emergency, and anesthesia. The DREEM questionnaire was used as a standard
tool. Data were analyzed using SPSS (v17) software. Student's t-tests and
analysis of variance (ANOVA) statistical tests were used. RESULTS: The mean of
the achieved scores in the five domains was 113.5 out of 200 (56.74%), which was
considered to be more positive than negative. The total mean scores for
perception of learning, teaching, and atmosphere were 27.4/48 (57.24%), 24.60/44
(55.91%), and 26.8/48 (55.89%), respectively. Academic and social self
perceptions were 20.5/32 (64.11%) and 15.7/28 (56.36%), respectively. The total
DREEM scores varied significantly between courses (P<0.01). The total scores of
the students of operating room nursing, anesthesia, and laboratory sciences,
first year students, and females were significantly higher than the other
students (P<0.01). CONCLUSION: The results have suggested that the students of
medical sciences courses at RUMS generally hold positive perceptions toward their
course environment. The differences between courses and their study pathway
should be further investigated by analysis of specific items. Our results showed
that it is essential for faculty members and course managers to make more efforts
toward observing principles of instructional designs, to create an appropriate
educational environment, and to reduce deficits in order to provide a better
learning environment with more facilities and supportive systems for the
students.
PMID- 25848332
TI - A learning skills course for the 1st year medical students: an experience at a
Saudi medical school.
AB - BACKGROUND: Every year nearly 1,500 students enter into medical program after
passing high school and national aptitude exams. However, many students
experience frustration, failure, and psychological morbidities like stress,
depression, and anxiety because they are not aware of their learning styles or do
not have effective learning skills and strategies. The College of Medicine of Al
Imam Muhammad ibn Saud Islamic University has adopted the outcome based,
community oriented, Spiral Curriculum. Although the curriculum is innovative, on
the other hand, it is very demanding. OBJECTIVE: The purpose of this paper is to
share educational structure and evaluation results of the course on effective
learning and study skills for the 1st year medical students. METHODS: To prepare
our students in order to cope with this demanding but promising curriculum, we
conducted an effective and comprehensive learning skills course for 16 weeks in
the first semester of year 1 in the medical program. Performance of each student
was assessed and the course evaluation was done by students at the end of the
course. RESULTS: The attendance of the students throughout the course was over
90%. The average performance of students in the summative assessment was 78% and
the course was generally liked by the students. DISCUSSION: Students overall had
a positive attitude toward the learning skills course. Majority of the students
showed interest in attending the sessions regularly and realized the significance
of this course to improve their learning skills.
PMID- 25848333
TI - Perceptions of students in different phases of medical education of the
educational environment: Universiti Sultan Zainal Abidin.
AB - BACKGROUND: The Dundee Ready Education Environment Measure (DREEM) was planned
and designed to quantify the educational environment precisely for medical
schools and health-related professional schools. DREEM is now considered a valid
and reliable tool, which is globally accepted for measuring the medical
educational environment. The educational environment encountered by students has
an impact on satisfaction with the course of study, perceived sense of well
being, aspirations, and academic achievement. In addition to being measurable,
the educational environment can also be changed, thus enhancing the quality of
medical education and the environment, and the medical education process. The
objective of this study was to assess the educational environment of the
Universiti Sultan Zainal Abidin (UniSZA) undergraduate medical program from the
students' perspective. The study expected to explore UniSZA medical students'
overall perceptions, perceptions of learning, teachers, atmosphere, academic self
perception, and social self-perception using the DREEM questionnaire. METHODS: A
cross-sectional survey was conducted to study the perceptions of the students
toward the educational environment of UniSZA as a new medical school, using the
DREEM questionnaire. All medical students of UniSZA from Years I-V enrolled in
the Bachelor of Medicine and Bachelor of Surgery programs were the target
population (n=270). Therefore, the universal sampling technique was used. The
data were analyzed using the SPSS 20 software. This study obtained ethical
clearance from the Faculty of Medicine and Health Sciences, UniSZA. RESULTS: A
total of 195 out of 270 students responded. Respondents included 31% males and
69% females. The overall DREEM scores were significantly higher (P<0.001) for
females than males. CONCLUSION: The medical students at UniSZA showed a positive
perception of their educational environment. The new medical faculty, established
for only a few years, has achieved an above-average, conducive educational
environment for students. Most of the students showed a positive perception for
the entire five domains tested in the DREEM survey. Females were consistently
satisfied with UniSZA's educational environment, and self-perception was high, as
compared to male undergraduates.
PMID- 25848334
TI - Preliminary investigation into application of problem-based learning in the
practical teaching of diagnostics.
AB - BACKGROUND: Problem-based learning (PBL) is a pedagogical approach based on
problems. Specifically, it is a student-centered, problem-oriented teaching
method that is conducted through group discussions. The aim of our study is to
explore the effects of PBL in diagnostic teaching for Chinese medical students.
METHODS: A prospective, randomized controlled trial was conducted. Eighty junior
clinical medical students were randomly divided into two groups. Forty students
were allocated to a PBL group and another 40 students were allocated to a control
group using the traditional teaching method. Their scores in the practice skills
examination, ability to write and analyze medical records, and results on the
stage test and behavior observation scale were compared. A questionnaire was
administered in the PBL group after class. RESULTS: There were no significant
differences in scores for writing medical records, content of interviewing,
physical examination skills, and stage test between the two groups. However,
compared with the control group, the PBL group had significantly higher scores on
case analysis, interviewing skills, and behavioral observation scales.
CONCLUSION: The questionnaire survey revealed that PBL could improve interest in
learning, cultivate an ability to study independently, improve communication and
analytical skills, and good team cooperation spirit. However, there were some
shortcomings in systematization of imparting knowledge. PBL has an obvious
advantage in teaching with regard to diagnostic practice.
PMID- 25848335
TI - Systemic targeted therapy for her2-positive early female breast cancer: a
systematic review of the evidence for the 2014 Cancer Care Ontario systemic
therapy guideline.
AB - BACKGROUND: This systematic review addresses the question "What is the optimal
targeted therapy for female patients with early-stage human epidermal growth
factor receptor 2 (her2)-positive breast cancer?" METHODS: The medline and embase
databases were searched for the period January 2008 to May 2014. The Standards
and Guidelines Evidence directory of cancer guidelines and the Web sites of major
guideline organizations were also searched. RESULTS: Sixty publications relevant
to the targeted therapy portion of the systematic review were identified. In four
major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31,
North Central Cancer Treatment Group N9831, and Breast Cancer International
Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free
survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no
benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1
year compared with 1 year) was evaluated, with mixed results for dfs: one trial
showed superiority (finher), one trial could not demonstrate noninferiority
(phare), another trial showed equivalent results (E 2198), and one trial is still
ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year)
showed no improvement in dfs or os and a higher rate of cardiac events. Newer
her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are
still being evaluated in both adjuvant and neoadjuvant trials, either by direct
comparison with trastuzumab alone or combined with trastuzumab. In the
neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in
combination with another anti-her2 agent (lapatinib, pertuzumab) was compared
with either lapatinib or pertuzumab alone and showed superior or equivalent rates
of pathologic complete response. In the adjuvant setting, lapatinib alone or in
combination with trastuzumab, compared with trastuzumab alone (altto) or with
placebo (teach), was not superior in dfs. The results of the completed aphinity
trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab,
are highly anticipated. Ongoing trials are evaluating trastuzumab as a single
agent without adjuvant chemotherapy (respect) and in patients with low her2
expression (National Surgical Adjuvant Breast and Bowel Project B-47).
CONCLUSIONS: Taking into consideration disease characteristics and patient
preference, 1 year of trastuzumab should be offered to all patients with her2
positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function
should be regularly assessed in this patient population.
PMID- 25848336
TI - Targeted therapy in her2-positive metastatic breast cancer: a review of the
literature.
AB - Breast tumours positive for her2 (human epidermal growth factor receptor 2)
represent approximately 20% of all breast cancer cases and are associated with an
aggressive natural history. The advent of targeted anti-her2 therapies has
dramatically improved disease control and survival in patients with metastatic
her2-positive breast cancer. Targeted agents are now considered the standard of
care in the first-line setting and beyond. The present review summarizes the
currently available data on targeted anti-her2 therapies from completed
randomized phase iii clinical trials and briefly discusses emerging advances that
will address unmet needs in metastatic her2-positive breast cancer.
PMID- 25848337
TI - Systemic treatment approaches in her2-negative advanced breast cancer-guidance on
the guidelines.
AB - Despite advancements in the treatment of early-stage breast cancer, many patients
still develop disease recurrence; others present with de novo metastatic disease.
For most patients with advanced breast cancer, the primary treatment intent is
noncurative-that is, palliative-in nature. The goals of treatment should
therefore focus on maximizing symptom control and extending survival. Treatments
should be evaluated on an individualized basis in terms of evidence, but also
with full respect for the wishes of the patient in terms of acceptable toxicity.
Given the availability of extensive reviews on the roles of endocrine therapy and
her2 (human epidermal growth factor receptor 2)-targeted therapies for advanced
disease, we focus here mainly on treatment guidelines for the non-endocrine
management of her2-negative advanced breast cancer in a Canadian health care
context.
PMID- 25848338
TI - A Canadian national expert consensus on neoadjuvant therapy for breast cancer:
linking practice to evidence and beyond.
AB - BACKGROUND: Use of the neoadjuvant approach to treat breast cancer patients has
increased since the early 2000s, but the overall pathway of care for such
patients can be highly variable. The aim of our project was to establish a
multidisciplinary consensus among clinicians with expertise in neoadjuvant
therapy (nat) for breast cancer and to determine if that consensus reflects
published methods used in randomized controlled trials (rcts) in this area.
METHODS: A modified Delphi protocol, which used iterative surveys administered to
85 experts across Canada, was established to obtain expert consensus concerning
all aspects of the care pathway for patients undergoing nat for breast cancer.
All rcts published between January 1, 1967, and December 1, 2012, were
systematically reviewed. Data extracted from the rcts were analyzed to determine
if the methods used matched the expert consensus for specific areas of nat
management. A scoring system determined the strength of the agreement between the
literature and the expert consensus. RESULTS: Consensus was achieved for all
areas of the pathway of care for patients undergoing nat for breast cancer, with
the exception of the role of magnetic resonance imaging in the pre-treatment or
preoperative setting. The levels of agreement between the consensus statements
and the published rcts varied, primarily because specific aspects of the pathway
of care were not well described in the reviewed literature. CONCLUSIONS: A true
consensus of expert opinion concerning the pathway of care appropriate for
patients receiving nat for breast cancer has been achieved. A review of the
literature illuminated gaps in the evidence about some elements of nat
management. Where evidence is available, agreement with expert opinion is strong
overall. Our study is unique in its approach to establishing consensus among
medical experts in this field and has established a pathway of care that can be
applied in practice for patients receiving nat.
PMID- 25848339
TI - Locoregional therapy of locally advanced breast cancer: a clinical practice
guideline.
AB - QUESTIONS: In female patients with locally advanced breast cancer (labc) and good
response to neoadjuvant chemotherapy (nact), including endocrine therapy, what is
the role of breast-conserving surgery (bcs) compared with mastectomy?In female
patients with labc, is radiotherapy (rt) indicated for those who have undergone
mastectomy?does locoregional rt, compared with breast or chest wall rt alone,
result in a higher survival rate and lower recurrence rates?is rt indicated for
those achieving a pathologic complete response (pcr) to nact?In female patients
with labc who receive nact, is the most appropriate axillary staging procedure
sentinel lymph node biopsy (slnb) or axillary dissection? Is slnb indicated
before nact rather than at the time of surgery?How should female patients with
labc that does not respond to initial nact be treated? METHODS: This guideline
was developed by Cancer Care Ontario's Program in Evidence-Based Care (pebc) and
the Breast Cancer Disease Site Group (dsg). A systematic review was prepared
based on literature searches conducted using the medline and embase databases for
the period 1996 to December 11, 2013. Guidelines were located from that search
and from the Web sites of major guideline organizations. The working group
drafted recommendations based on the systemic review. The systematic review and
recommendations were then circulated to the Breast Cancer dsg and the pebc Report
Approval Panel for internal review; the revised document underwent external
review. The full three-part evidence series can be found on the Cancer Care
Ontario Web site. RECOMMENDATIONS: For most patients with labc, modified radical
mastectomy should be considered the standard of care. For some patients with
noninflammatory labc, bcs can be considered on a case-by-case basis when the
surgeon deems that the disease can be fully resected and the patient expresses a
strong preference for breast preservation.For patients with labc, rt after
mastectomy is recommended.It is recommended that, after bcs or mastectomy,
patients with labc receive locoregional rt encompassing the breast or chest wall
and local node-bearing areas.It is recommended that postoperative rt remain the
standard of care for patients with labc who achieve pcr to nact.It is recommended
that axillary dissection remain the standard of care for axillary staging in
labc, with the judicious use of slnb in patients who are advised of the
limitations of the current data.Although slnb either before or after nact is
technically feasible, the data are insufficient to make any recommendation about
the optimal timing of slnb with respect to nact. Limited data suggest higher
sentinel lymph node identification rates and lower false negative identification
rates when slnb is conducted before nact; however, those data must be balanced
against the requirement for two operations if slnb is not performed at the time
of resection of the main tumour.It is recommended that patients receiving
neoadjuvant anthracycline-taxane-based therapy (or other sequential regimens)
whose tumours do not respond to the initial agent or agents, or who experience
disease progression, be expedited to the next agent or agents of the regimen.For
patients who, in the opinion of the treating physician, fail to respond or
progress on first-line nact, several therapeutic options can be considered,
including second-line chemotherapy, hormonal therapy (if appropriate), rt, or
immediate surgery (if technically feasible). Treatment should be individualized
through discussion at a multidisciplinary case conference, considering tumour
characteristics, patient factors and preferences, and risk of adverse effects.It
is recommended that prospective randomized clinical trials be designed for
patients with labc who fail to respond to nact so that more definitive treatment
recommendations can be developed.
PMID- 25848341
TI - The best available evidence ... all in one place.
PMID- 25848340
TI - Optimal systemic therapy for early breast cancer in women: a clinical practice
guideline.
AB - The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need
for new guidelines for the adjuvant systemic therapy of early-stage breast
cancer. The specific question to be addressed was "What is the optimal adjuvant
systemic therapy for female patients with early-stage operable breast cancer,
when patient and disease factors are considered?" A systematic review was
prepared based on literature searches conducted using the medline and embase
databases for the period January 2008 to March 5, 2012, and updated to May 12,
2014. Guidelines were located from that search, from the Standards and Guidelines
Evidence directory of cancer guidelines, and from the Web sites of major
guideline organizations. The literature located was subdivided into the broad
categories of chemotherapy, hormonal therapy, and therapy targeted to her2 (human
epidermal growth factor receptor 2). Although several of the systemic therapies
discussed in this guideline can be considered in the neoadjuvant setting, the
review focused on trials with rates of disease-free and overall survival as
endpoints and thus excluded several trials that used pathologic complete response
as a primary endpoint. Based on the systematic review, the working group drafted
recommendations on the use of chemotherapy, hormonal therapy, and targeted
therapy; based on their professional experience, they also drafted
recommendations on patient and disease characteristics and recurrence risk. The
literature review and draft recommendations were circulated to a consensus panel
of medical oncologists who had expertise in breast cancer and who represented the
regions of Ontario. Items without initial consensus were discussed at an in
person consensus meeting held in Toronto, November 23, 2012. The final
recommendations are those for which consensus was reached before or at the
meeting. Some of the key evidence was revised after the updated literature
search. Evidence reviews for systemic chemotherapy, endocrine therapy, and
targeted therapy for her2-positive disease are reported in separate articles in
this supplement. The full three-part 1-21 evidence-based series, including
complete details of the development and consensus processes, can be found on the
Cancer Care Ontario Web site at
https://www.cancercare.on.ca/toolbox/qualityguidelines/diseasesite/breast-ebs.
PMID- 25848342
TI - Outcome of patients with pregnancy during or after breast cancer: a review of the
recent literature.
AB - BACKGROUND: An increasing number of young women are delaying childbearing; hence,
more are diagnosed with breast cancer (bca) before having a family. No clear
recommendations are currently available for counselling such a population on the
safety of carrying a pregnancy during bca or becoming pregnant after treatment
for bca. METHODS: Using a Web-based search of PubMed we reviewed the recent
literature about bca and pregnancy. Our objective was to report outcomes for
patients diagnosed with bca during pregnancy, comparing them with outcomes for
non-pregnant women, and to evaluate prognosis in women diagnosed with and treated
for bca who subsequently became pregnant. RESULTS: "Pregnancy and bca" should be
divided into two entities. Pregnancy-associated bca tends to be more aggressive
and advanced in stage at diagnosis than bca in control groups; hence, it has a
poorer prognosis. With respect to pregnancy after bca, there is, despite the bias
in reported studies and meta-analyses, no clear evidence for a different or worse
disease outcome in bca patients who become pregnant after treatment compared with
those who do not. CONCLUSIONS: Pregnancy-associated bca should be treated as
aggressively as and according to the standards applicable in nonpregnant women;
pregnancy after bca does not jeopardize outcome. The guidelines addressing risks
connected to pregnancy and bca lack a high level of evidence for better
counselling young women about pregnancy considerations and preventing unnecessary
abortions. Ideally, evidence from large prospective randomized trials would set
better guidelines, and yet the complexity of such studies limits their
feasibility.
PMID- 25848345
TI - Robust estimation of marginal regression parameters in clustered data.
AB - We develop robust methods for analyzing clustered data where estimation of
marginal regression parameters is of interest. Inverse cluster size reweighting
in the objective function to be minimized is incorporated to handle the issue of
informative cluster size. Performance of the resulting estimators is studied by
simulation. Large sample inference and variance estimation is carried out. The
methodology is illustrated using a periodontal disease dataset.
PMID- 25848343
TI - Adjuvant chemotherapy for early female breast cancer: a systematic review of the
evidence for the 2014 Cancer Care Ontario systemic therapy guideline.
AB - BACKGROUND: The Program in Evidence-Based Care (pebc) of Cancer Care Ontario
recently created an evidence-based consensus guideline on the systemic treatment
of early breast cancer. The evidence for the guideline was compiled using a
systematic review to answer the question "What is the optimal systemic therapy
for patients with early-stage, operable breast cancer, when patient and disease
factors are considered?" The question was addressed in three parts: cytotoxic
chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2
(her2)-directed therapy. METHODS: For the systematic review, the medline and
embase databases were searched for the period January 2008 to May 2014. The
Standards and Guidelines Evidence directory of cancer guidelines and the Web
sites of major oncology guideline organizations were also searched. The basic
search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine
therapy, targeted agents, ovarian suppression), and results were limited to
randomized controlled trials (rcts), guidelines, systematic reviews, and meta
analyses. RESULTS: Several hundred documents that met the inclusion criteria were
retrieved. The Early Breast Cancer Trialists' Collaborative Group meta-analyses
encompassed many of the rcts found. Several additional studies that met the
inclusion criteria were retained, as were other guidelines and systematic
reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite-based
regimens (for example, cyclophosphamide-methotrexate-5-fluorouracil),
anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy
is not recommended for the adjuvant treatment of breast cancer in any patient
population. Anthracycline-taxane-based polychemotherapy regimens are, overall,
considered superior to earlier-generation regimens and have the most significant
impact on patient survival outcomes. Regimens with varying anthracycline and
taxane doses and schedules are options; in general, paclitaxel given every 3
weeks is inferior. Evidence does not support the use of bevacizumab in the
adjuvant setting; other systemic therapy agents such as metformin and vaccines
remain investigatory. Adjuvant bisphosphonates for menopausal women will be
discussed in later work. CONCLUSIONS: The results of this systematic review
constitute a comprehensive compilation of the high-level evidence that is the
basis for the 2014 pebc guideline on systemic therapy for early breast cancer.
Use of cytotoxic chemotherapy is presented here; the results addressing endocrine
therapy and her2-targeted treatment, and the final clinical practice
recommendations, are published separately in this supplement.
PMID- 25848346
TI - Epidemiology and Clinical Research Design, Part 1: Study Types.
AB - Selecting the best available preventive and therapeutic measures to avoid
disability and death is an important goal for all health care practitioners. To
achieve this goal, we need to perform studies that determine the value of these
measures. In this article, we discuss the possible study designs that can be used
for evaluating new approaches to prevention and treatment. The gold standard
study design is a randomized, controlled, double-blind trial. In many instances,
a randomized controlled trial may not be ethically or practically feasible. Other
study types, such as case series, case-control studies, cohort studies, cross
sectional studies, crossover designs, and open-label studies, may be required to
hypothesize and evaluate the link between an exposure or predictor variable and
an outcome variable. Various study types pertaining to neonatal-perinatal
medicine are reviewed in this article.
PMID- 25848344
TI - Adjuvant endocrine therapy for early breast cancer: a systematic review of the
evidence for the 2014 Cancer Care Ontario systemic therapy guideline.
AB - BACKGROUND: Cancer Care Ontario's Program in Evidence-Based Care (pebc) recently
created an evidence-based consensus guideline on the systemic treatment of early
breast cancer. The evidence for the guideline was compiled using a systematic
review to answer the question "What is the optimal systemic therapy for patients
with early-stage, operable breast cancer, when patient and disease factors are
considered?" The question was addressed in three parts: cytotoxic chemotherapy,
endocrine treatment, and her2 (human epidermal growth factor receptor 2)-targeted
therapy. METHODS: For the systematic review, the literature in the medline and
embase databases was searched for the period January 2008 to May 2014. The
Standards and Guidelines Evidence directory of cancer guidelines and the Web
sites of major oncology guideline organizations were also searched. The basic
search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine
therapy, targeted agents, ovarian suppression), and results were limited to
randomized controlled trials (rcts), guidelines, systematic reviews, and meta
analyses. RESULTS: Several hundred documents that met the inclusion criteria were
retrieved. Meta-analyses from the Early Breast Cancer Trialists' Collaborative
Group encompassed many of the rcts found. Several additional studies that met the
inclusion criteria were retained, as were other guidelines and systematic
reviews. SUMMARY: The results of the systematic review constitute a comprehensive
compilation of high-level evidence, which was the basis for the 2014 pebc
guideline on systemic therapy for early breast cancer. The review of the evidence
for systemic endocrine therapy (adjuvant tamoxifen, aromatase inhibitors, and
ovarian ablation and suppression) is presented here; the evidence for
chemotherapy and her2-targeted treatment-and the final clinical practice
recommendations-are presented separately in this supplement.
PMID- 25848347
TI - Long-Term Response of Classic Kaposi's Sarcoma to Intralesional Doxorubicin: A
Case Report.
AB - Classic Kaposi's sarcoma (KS) is a disease with low mortality but high morbidity.
The optimum treatment of KS depends upon several factors, including location of
lesions, disease progression, severity of symptoms and patient preference. We
report the long-term response to the use of intralesional doxorubicin to
successfully treat a large cutaneous lesion of KS on a patient refractory to
traditional treatments.
PMID- 25848348
TI - Basal cell carcinoma arising on a verrucous epidermal nevus: a case report.
AB - We report a case of basal cell carcinoma that appeared from an epidermal
verrucous nevus in a 61-year-old patient. The onset of basal cell carcinoma in
sebaceous nevi, basal cell nevi and dysplastic nevi is relatively common, but it
is rarely associated with epidermal verrucous nevi. There is no consensus on
whether the two lesions have a common cellular origin or whether they merely
represent a collision of two distinct tumors. Since this association - as with
other malignant tumors - is rare, there is no need for prophylactic removal of
epidermal verrucous nevi.
PMID- 25848349
TI - Perianal Basal cell carcinoma.
AB - Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. Exposure
to ultraviolet light is an important risk factor for BCC development and the
disorder therefore develops commonly on body areas that are more exposed to
sunlight, such as the face and neck. It is uncommon in the closed area of the
body and quite rare in the perianal and genital regions. Herein, we report a 34
year-old patient with perianal BCC who had no additional risk factors.
PMID- 25848350
TI - A Case of Old Age-Onset Generalized Pustular Psoriasis with a Deficiency of IL
36RN (DITRA) Treated by Granulocyte and Monocyte Apheresis.
AB - A 78-year-old woman who had been suffering from psoriasis vulgaris for 31 years
was admitted to hospital because of her erythroderma. A toxic eruption was
suspected and she was treated with prednisolone 30 mg daily. However, it was
ineffective and, suspecting psoriatic erythroderma, cyclosporine 150 mg daily was
administered with tapering of the prednisolone. Two weeks after a dose reduction
of cyclosporine to 100 mg/day, erythroderma with widespread generalized pustules
and fever developed. Histology of a biopsy revealed inflammatory infiltrates in
the skin with a spongiform pustule of Kogoj, which was consistent with
generalized pustular psoriasis (GPP). Her pustules improved with additional
etretinate 20 mg/day, but the erythroderma persisted and she consulted us. Three
sessions of granulocyte and monocyte apheresis once weekly were effective for her
condition and decreased her serum levels of IL-6 and IL-8. She had homozygous
mutations of c.[28C>T] in IL36RN which cause p.[Arg10Ter]. She is the oldest
reported case of GPP with a deficiency of interleukin-36 receptor antagonist
(DITRA), although GPP in DITRA has been suggested to usually occur in younger
cases with no pre-existing psoriasis vulgaris.
PMID- 25848352
TI - A case of contiguous primary hepatic marginal zone B-cell lymphoma and hemangioma
ultimately diagnosed using contrast-enhanced ultrasonography.
AB - Primary hepatic marginal zone B-cell malignant lymphoma of mucosa-associated
lymphoid tissue (MALT lymphoma) is extremely rare. We present a case in which a
lesion was diagnosed as 2 contiguous tumors (MALT lymphoma and hemangioma) using
contrast-enhanced ultrasonography (US) with sonazoid. There has been no previous
case of contiguous hepatic MALT lymphoma and hemangioma. The present case was a
female with no medical history. We detected a snowman-like appearance, which was
a tumor of 15 mm in diameter with hypo- and hyper-echogenicities in the lateral
and medial parts, respectively, in the Couinaud's segment (S6) of the liver on
US. The tumor appeared as a single lesion with a low-density area in the
unenhanced phase and prolonged enhancement in the equilibrium phases on dynamic
CT. On MRI, the whole lesion showed a low-intensity signal on T1-weighted
imaging, but isointensity in the lateral part and high intensity in the medial
part were seen on T2-weighted imaging. On contrast-enhanced US, the lateral
hypoechoic region was homogenously hyperenhanced in the early vascular phase, and
the contrast medium was washed out after about 30 s; in contrast, the medial
hyperechoic region was gradually stained from the margin toward the central
region. The tumor showed a defect in both hypo- and hyperechoic regions in the
postvascular phase. Hemangioma was suspected for the medial part based on the
typical image findings, but the lateral part was not given a diagnosis. Thus,
surgical resection was performed. The medial part was a hemangioma, and the
lateral part was a MALT lymphoma by histopathological findings.
PMID- 25848351
TI - How early can pancreatic cancer be recognized? A case report and review of the
literature.
AB - The early symptoms of pancreatic cancer are often very vague. They may precede
the diagnosis by years and go unrecognized. This makes pancreatic cancer one of
the cancers with the worst survival rates. The progression rate of the early
phase might be slower than previously thought. Here, we report a case where
symptoms, including thromboembolism and new-onset diabetes mellitus, preceded the
diagnosis of pancreatic cancer by 6 years or longer. The awareness of the early
symptoms of pancreatic cancer is required for being vigilant and further
diagnostic tests. A simple clinical model utilizing certain risk factors and
symptoms for pancreatic cancer will help stratify the patients for further
screening tests.
PMID- 25848354
TI - Korean medicine therapy as a substitute for chemotherapy for metastatic breast
cancer: a case report.
AB - A 46-year-old Korean woman was diagnosed with stage III breast cancer and
underwent 8 cycles of neoadjuvant chemotherapy, breast conservation surgery and
adjuvant radiotherapy. However, the cancer recurred in the right upper lung (RUL)
and the right pulmonary hilum after 8 months. The RUL nodule was removed through
a wedge resection, and the pathologic finding was revealed as a metastatic
adenocarcinoma. Adjuvant chemotherapy was recommended, but she refused it because
she feared adverse reactions to chemotherapy. Instead, Korean Medicine Therapy
with intravenous wild ginseng pharmacopuncture (WGP), Cordyceps sinensis
pharmacopuncture, Trichosanthes kirilowii pharmacopuncture, Euonymus alatus
pharmacopuncture (EAP) and Astragalus membranaceus pharmacopuncture was started.
After a month, the disease looked stable, but findings of newly occurring
metastatic lymphadenopathies appeared on CT after 6 months. Salvage chemotherapy
was recommended, but she also refused it. At this time, Prunella vulgaris
pharmacopuncture was started. Finally, a complete resolution was confirmed on PET
CT after 5 months, and she has remained in stable condition for more than 6
months with WGP, EAP, a Soram nebulizer solution inhalation and the oral intake
of Soramdan S and Hangamdan S.
PMID- 25848353
TI - Multiple myeloma and atopic eczema in an adult.
AB - Multiple myeloma is the fourteenth cause of cancer-related death. The symptoms of
myeloma are mostly nonspecific, and there is significant delay between the first
symptoms and diagnosis of myeloma. Atopic eczema is a common chronic inflammatory
skin disease associated with dysregulation of the immune system. It generally
develops in early childhood but can also occur in adults. Eczema is associated
with a variety of hematological and solid malignancies, and possibly multiple
myeloma. We report a patient with eczema that developed 5 years before the
diagnosis of multiple myeloma but was mistaken for psoriasis.
PMID- 25848355
TI - Prolonged Response and Restoration of Functional Independence with Bevacizumab
plus Vinorelbine as Third-Line Treatment for Breast Cancer-Related Leptomeningeal
Metastases.
AB - BACKGROUND: Survival of patients with leptomeningeal metastases (LM) and impaired
functional status is limited to several months, and rarely does neurological
function improve with treatment. CASE REPORT: A 34-year-old female with hormone
negative and HER2-positive metastatic breast cancer was diagnosed with bulky
radiographic LM 45 months after initial diagnosis. She was treated with intra-CSF
trastuzumab followed by intra-CSF liposomal cytarabine; however, the cancer
progressed 8 months after the diagnosis of LM. At the time of the third LM
progression, the patient presented with a cauda equina syndrome and cerebellar
impairment resulting in an inability to walk. She was treated with CNS-directed
radiotherapy (lumbosacral and cerebellar) and bevacizumab plus vinorelbine. Rapid
functional improvement occurred, and the patient regained the ability to walk and
independently manage her daily activities. Twelve months later, she presented
with rapid progression of the LM resulting in death within several weeks.
CONCLUSION: In radiographically defined bulky LM, the combination of systemic
therapy and CNS-directed radiotherapy likely is more active than intra-CSF
therapy only. In lieu of the rapid and significant improvement in neurological
function combined with the prolonged response, bevacizumab alone or in
combination with chemotherapy and CNS-directed radiotherapy may be considered in
select patients with radiographically bulky breast cancer-related LM.
PMID- 25848356
TI - Pharmacokinetics of gefitinib in a patient with non-small cell lung cancer
undergoing continuous ambulatory peritoneal dialysis.
AB - A 72-year-old man undergoing continuous ambulatory peritoneal dialysis (CAPD) for
chronic renal failure and who had undergone right upper lobectomy for lung
adenocarcinoma (pT2aN0M0) 2 years ago was admitted for recurrence of lung cancer
presenting as multiple brain metastases. An epidermal growth factor receptor
mutation analysis of his lung cancer revealed a deletion of 15 nucleotides (E746
A750) in exon 19. After whole-brain radiotherapy, we started daily administration
of 250 mg gefitinib under the continuation of CAPD and performed a
pharmacokinetic analysis. We speculated that the plasma concentration of
gefitinib reached the steady state at least by day 16 after the start of
gefitinib (626.6 ng/ml at trough level). On day 46, the plasma concentration was
538.4 ng/ml at trough level and the concentration in the peritoneal dialysis
fluid was 34.6 ng/ml, suggesting that CAPD appeared to have little effect on the
pharmacokinetics of gefitinib. During gefitinib therapy, there were no
significant adverse events except for grade 2 diarrhea. Gefitinib could be safely
administered to a patient undergoing CAPD.
PMID- 25848357
TI - Clinical Response to Sorafenib in a Patient with Metastatic Colorectal Cancer and
FLT3 Amplification.
AB - BACKGROUND: A considerable number of patients with metastatic colorectal cancer
progress after exhausting all approved standard therapies but maintain an
adequate performance status and could be candidates for further treatment. We aim
at reviewing our experience with sorafenib treatment of a patient with FLT3
mutation in refractory metastatic colorectal cancer. METHODS: Treatment with
sorafenib of a patient with metastatic colorectal cancer and FLT3 translocation
who had previously been heavily treated. RESULTS: The patient with metastatic
colorectal cancer, aged 51 years, showed significant symptomatic and laboratory
improvement with sorafenib treatment (400 mg twice daily). CONCLUSION: The
presented case illustrates how an aggressive and refractory colorectal tumor may
respond well to targeted therapy.
PMID- 25848358
TI - Tyrosine kinase inhibitor induced isolated pericardial effusion.
AB - Long-term therapy with tyrosine kinase inhibitors (TKI) has resulted in improved
outcomes for patients suffering from Bcr-Abl fusion protein-harboring leukemias.
As a result, a growing population of patients on TKI therapy present to their
primary care providers. In this case, we report on the case of a 62-year-old male
who presented with a symptomatic pericardial effusion. After pericardiocentesis,
malignancy and infectious etiologies were excluded. The pericardial effusion was
attributed to his TKI, with a transition of this medication to a different TKI. A
repeat evaluation 1 month following the withdrawal of the offending agent showed
no recurrence of his pericardial effusion on echocardiogram. In this report, we
will highlight a rare but important side effect of TKI therapy before discussing
its purported mechanisms and differing incidence rates. Early recognition of
serosal inflammation related to long-term TKI therapy by primary care providers
is important in preventing patient morbidity and mortality.
PMID- 25848359
TI - Spontaneous regression of hepatocellular carcinoma: its imaging course leading to
complete disappearance.
AB - Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We
followed a detailed clinical course of a spontaneous and complete disappearance
of HCC during a short interval. A 73-year-old man with hepatitis B virus
infection presented with a 15-mm mass in the right anterior superior segment of
the liver. The mass was diagnosed as HCC by imaging findings. We found an
elevated serum alpha-fetoprotein (AFP) level of 748 ng/ml. The tumor regressed to
6 mm on imaging examination, and the AFP serum level decreased to 87.8 ng/ml 1
month after the diagnostic hepatic angiography. Therefore, the patient was
followed up without any treatment for HCC. The tumor disappeared 5 months later
when the AFP serum level was 5.0 ng/ml. The diagnostic hepatic angiography might
have had some effect on the spontaneous regression of HCC in the present case.
PMID- 25848360
TI - A Case of Disease Improvement after Treatment with Everolimus plus Exemestane in
a Patient with Hormone Receptor-Positive Metastatic Breast Cancer with Bone
Metastases.
AB - Breast cancer is one of the most frequently diagnosed cancers and a leading cause
of death in women worldwide. Despite significant advances in the treatment of
hormone receptor-positive breast cancer, tumor metastasis occurs frequently and
is associated with poor long-term prognosis. The mammalian target of rapamycin
(mTOR) pathway plays a central role in cancer cell growth, proliferation, and
resistance to endocrine therapies. Therefore, mTOR inhibitors such as everolimus
in combination with nonsteroidal aromatase inhibitors might reverse endocrine
resistance and improve clinical outcomes in patients. Here, we report on a case
of infiltrating lobular carcinoma of the breast with metastases to the bone.
Histopathologic analysis showed that the patient was estrogen and progesterone
receptor positive and human epidermal growth factor-2 negative. This case
represents the clinical spectrum of complications caused by metastasis: the
patient experienced a considerable amount of skeletal-related complications, had
previously received chemotherapy, and experienced disease progression while
taking nonsteroidal aromatase inhibitors. After treatment with oral everolimus 10
mg daily plus oral exemestane 25 mg daily, the patient's disease was ameliorated.
Combination therapy was well tolerated, with minimal adverse effects that were
manageable with concomitant medications. Although further analyses in larger
populations are necessary, the addition of everolimus to exemestane might provide
an effective new treatment option for patients with bone metastasis.
PMID- 25848361
TI - Sebaceous carcinoma of the parotid gland: a case report.
AB - BACKGROUND: Primary sebaceous carcinoma of the parotid gland is extremely rare,
and because of its rarity, clinicopathological characteristics and histogenesis
are not fully understood. METHODS: Here, we report a patient who presented with a
left infra-auricular painless mass. We present the histological features and
discuss possible optimal treatments based on previous literature. RESULTS: The
mass was suspected to be a myoepithelial tumor or possibly a pleomorphic adenoma.
Initially, the mass was resected with preservation of the facial nerve, but this
caused facial palsy. Because the histological examination showed a sebaceous
carcinoma and a part of the mass could be remaining on the facial nerve,
additional surgery was performed, and the facial nerve was reconstructed with
cervical nerve. Follow-up after 7 months showed no sign of recurrence of
metastasis. CONCLUSION: We encountered a rare sebaceous carcinoma of the parotid
gland. Additional surgery was performed because preoperative diagnosis was
difficult.
PMID- 25848362
TI - Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.
PMID- 25848363
TI - How to walk the tightrope between harm and protection in selecting the optimal
antiplatelet treatment strategy after transcatheter left atrial appendage
occlusion.
PMID- 25848364
TI - Non-ST elevation myocardial infarction related to total coronary artery occlusion
- prevalence and patient characteristics.
AB - INTRODUCTION: Acute coronary occlusion (ACO) may also present as non-ST elevation
myocardial infarction (NSTEMI) and thus veil the real threat. AIM: Based on
combined analysis of electrocardiography and echocardiography findings, we aimed
to describe profile of NSTEMI patients at increased risk of ACO. MATERIAL AND
METHODS: It was a retrospective study that included patients referred for cardiac
catheterisation due to NSTEMI. Patients were selected into the study in two
different time frames. Firstly, all consecutive NSTEMI patients were enrolled in
a 12-month period to detect the prevalence of ACO (prevalence group). Secondly,
all NSTEMI patients with ACO hospitalized in the previous 5 years were also
enrolled (NSTEMI-ACO group). All patients had 12-lead electrocardiogram (ECG) and
the transthoracic echocardiography (TTE) performed before the cardiac
catheterisation. RESULTS: Fifty-three consecutive patients (37 males) were
enrolled into the prevalence group in a 12-month period. Ten (19%) of them were
diagnosed with ACO. Thirty-four consecutive patients were enrolled into the
NSTEMI-ACO group. Non-ST elevation myocardial infarction patients with ACO were
younger as compared to NSTEMI patients without ACO. Non-ST elevation myocardial
infarction patients with ACO were less likely to have anterior wall ischaemia as
detected by ECG, which was not reflected by TTE results. Combined assessment of
ischaemia by ECG and impaired contractility by TTE did not reveal any significant
differences between NSTEMI patients with or without ACO. CONCLUSIONS: The
identification of NSTEMI patients with ACO is challenging. Therefore, the utmost
caution should be paid to prevent delay of coronary angiography in NSTEMI
patients who have increased risk of ACO.
PMID- 25848365
TI - Percutaneous closure of the left atrial appendage for secondary prevention of
stroke in patients with atrial fibrillation and contraindications to chronic
anticoagulant therapy.
AB - INTRODUCTION: Stroke accounts for approx. 90% of thromboembolic complications
associated with atrial fibrillation. The use of oral anticoagulants is the most
effective therapy but is associated with risk of haemorrhagic complications. AIM:
In this article, we describe a series of patients with atrial fibrillation,
cardiogenic stroke history, and contraindications for long-term anticoagulant
therapy, in whom an alternative method - percutaneous closure of the left atrial
appendage - was performed. MATERIAL AND METHODS: Nine patients with atrial
fibrillation and previous stroke were qualified for percutaneous closure of the
left atrial appendage (5 men and 4 women, aged 45-78 years). Physical and
neurological examinations were conducted in the qualification period, 1-3 days
before the intervention, and 1-3 days and 1, 3, 6, 12, and 24 months following
percutaneous closure of the left atrial appendage. Transoesophageal
echocardiography was carried out in the qualification period, 1-3 days before the
intervention, and at 1-3 days and 3 and 6 months following the procedure.
RESULTS: No complications were observed in the perioperative period and during
the follow-up period of 16-31 months. Echocardiographic examinations showed that
occluders were present in the appropriate positions. CONCLUSIONS: Percutaneous
closure of the left atrial appendage can be an alternative form of secondary
prevention of stroke in patients with atrial fibrillation and contraindications
for long-term anticoagulant therapy or those who have problems managing drug
treatment. Complex clinical assessment performed by a neuro-cardiac team allows
safe and efficient invasive treatment.
PMID- 25848366
TI - Antiplatelet resistance and the role of associated variables in stable patients
treated with stenting.
AB - INTRODUCTION: Nowadays, clopidogrel and acetylsalicylic acid (ASA) have become
routinely applied therapies in percutaneous coronary interventions (PCI) with
stenting. AIM: Numerous variables can interfere with antiplatelet responsiveness,
so we aimed to investigate the role of different variables associated with ASA or
clopidogrel resistance in stable coronary artery disease. MATERIAL AND METHODS: A
total of 207 patients undergoing elective PCI were included in the analysis. All
patients received a loading dose of clopidogrel and ASA during PCI procedure and
followed by dual antiplatelet therapy. Clopidogrel and ASA resistance were
measured by impedance aggregometry method. RESULTS: Of the patients, 19.8% had
clopidogrel resistance, 18.8% had ASA resistance, 9.2% had both clopidogrel and
ASA resistance, and 71.5% were responsive to both drugs. In multivariate
analysis, platelet count, angiotensin receptor blocker (ARB) use, and ASA
resistance were independent variables associated with clopidogrel resistance, and
clopidogrel resistance was the only variable associated with ASA resistance. In
differentiating whether clopidogrel resistance exists or not, optimum ASA
aggregometry response cut-off values were specified, and in differentiating
whether ASA resistance exists or not, optimum clopidogrel aggregometry response
cut-off values were specified. CONCLUSIONS: In this study, there was a higher
incidence of low responsiveness to ASA when there was a low response to
clopidogrel, and vice versa. Angiotensin receptor blocker use, platelet count,
and ASA resistance were independent variables associated with clopidogrel
resistance. Clopidogrel resistance was the only independent variable associated
with ASA resistance. Angiotensin receptor blocker use seems to an independent
risk factor for clopidogrel resistance in this study, but this result needs to be
verified in other studies.
PMID- 25848367
TI - The relationship between rheumatoid factor levels and coronary artery lesion
complexity and severity in patients with stable coronary artery disease.
AB - INTRODUCTION: The relation between serum rheumatoid factor levels and the extent,
severity, and complexity of coronary artery disease has not been adequately
studied. AIM: Therefore, we assessed the relationship between the severity of
coronary artery disease assessed by SYNTAX score and serum rheumatoid factor
levels in patients with stable coronary artery disease. MATERIAL AND METHODS: We
enrolled 268 consecutive patients who underwent coronary angiography. Patients
with acute coronary syndrome and chronic immune disorders were excluded. Baseline
serum rheumatoid factor levels were measured and the SYNTAX score was calculated
from the study population. RESULTS: Patients were divided into two groups. Group
1 was defined as low SYNTAX score < 22, and group 2 was defined as intermediate
and high SYNTAX score > 22. Serum rheumatoid factor levels were significantly
higher in the intermediate and high-SYNTAX score group than in the low-SYNTAX
score group (16.4 +/-9 IU/mlvs. 11.36 +/-5 IU/ml, p < 0.001). Also, there was a
significant correlation between rheumatoid factor and CRP levels with the SYNTAX
score r = 0.411; p < 0.001 and r = 0.275; p < 0.001, respectively. On
multivariate linear regression analysis, rheumatoid factor (beta = 0.101, p <
0.001) was an independent risk factor for intermediate and high SYNTAX score in
patients with stable coronary artery disease. In receiver operator characteristic
curve analysis, optimal cut-off value of rheumatoid factor to predict high SYNTAX
score was found to be 10.5 IU/ml, with 69% sensitivity and 61% specificity.
CONCLUSIONS: The rheumatoid factor level was independently associated with the
extent, complexity, and severity of coronary artery disease assessed by SYNTAX
score in patients with stable coronary artery diseases.
PMID- 25848368
TI - Transradial approach for vertebral artery stenting.
AB - INTRODUCTUION: Symptomatic severe vertebral artery (VA) stenosis may be treated
safely with stent supported angioplasty via femoral access. There is limited
clinical data on transradial approach for VA angioplasty in case of peripheral
artery disease. AIM: To evaluate the safety and efficacy of transradial
angioplasty of symptomatic VA stenosis. MATERIAL AND METHODS: Fifteen patients
(age 66 +/-7.4 years, 73% men, with VA > 80% stenosis, 11 right-side, all
symptomatic from posterior circulation (history of stroke, TIA, or chronic
ischaemia symptoms)) with peripheral artery disease (PAD) or unsuccessful attempt
via femoral approach were scheduled for VA angioplasty by radial access. Clinical
and duplex ultrasound (DUS) follow-up were performed before discharge and 1, 12,
and 24 months after VA angioplasty. RESULTS: The technical success rate was 100%.
In all cases VA angioplasty was performed with the use of single balloon-mounted
stent (9 bare metal stents, 6 drug-eluting stents). The mean NASCET VA stenosis
was reduced from 85.3% to 5.3% (p < 0.001). No periprocedural death, stroke,
myocardial infarction, or transient ischaemic attack occurred. During 24-months
follow-up, in 12 of 15 patients chronic ischaemia symptoms release was observed,
and no new acute ischaemic neurological symptoms were diagnosed in all patients.
One patient died 20 months after intervention from unknown causes. There was one
symptomatic borderline VA in-stent stenosis 12 months after angioplasty.
CONCLUSIONS: Transradial VA stenting may be a very effective and safe procedure,
and it may constitute an alternative to the femoral approach in patients with
symptomatic VA stenosis.
PMID- 25848370
TI - Stenting of the right ventricular outflow tract in a symptomatic newborn with
tetralogy of Fallot.
AB - This case describes a successful percutaneous stent implantation to critical
stenosis of the right ventricle outflow tract in a female neonate with tetralogy
of Fallot. At the time of the procedure she had poor development of the pulmonary
arteries (McGoon and Nakata index 1.45 and 120, respectively). Stent implantation
ensured an immediate increase in oxygen saturation level, and the physiological
pulsating blood inflow caused good development of the pulmonary arteries during
12 months of follow up (McGoon 2.5; Nacata Index 436). After this time she was
qualified for surgery and underwent surgical correction without using a patch or
conduit implantation.
PMID- 25848369
TI - The impact of transcatheter aortic valve implantation on left ventricular
performance and wall thickness - single-centre experience.
AB - INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a treatment
alternative for the elderly population with severe symptomatic aortic stenosis
(AS) at high risk for surgical aortic valve replacement (SAVR). AIM: To assess
the impact of TAVI on echocardiographic parameters of left ventricular (LV)
performance and wall thickness in patients subjected to the procedure in a single
centre between 2009 and 2013. MATERIAL AND METHODS: The initial group consisted
of 170 consecutive patients with severe AS unsuitable for SAVR. Logistic European
System for Cardiac Operative Risk Evaluation (EuroSCORE) was 21.73 +/-12.42% and
mean age was 79.9 +/-7.5 years. RESULTS: The TAVI was performed in 167 (98.2%)
patients. Mean aortic gradient decreased significantly more rapidly after the
procedure (from 58.6 +/-16.7 mm Hg to 11.9 +/-4.9 mm Hg, p < 0.001). The LV
ejection fraction (LVEF) significantly increased in both short-term and long-term
follow-up (57 +/-14% vs. 59 +/-13%, p < 0.001 and 56 +/-14% vs. 60 +/-12%, p <
0.001, respectively). Significant regression of interventricular septum diameter
at end-diastole (IVSDD) and end-diastolic posterior wall thickness (EDPWth) was
noted in early (15.0 +/-2.4 mm vs. 14.5 +/-2.3 mm, p < 0.001 and 12.7 +/-2.1 mm
vs. 12.4 +/-1.9 mm, p < 0.028, respectively) and late post-TAVI period (15.1 +/
2.5 mm to 14.3 +/-2.5 mm, p < 0.001 and 12.8 +/-2.0 mm to 12.4 +/-1.9 mm, p <
0.007, respectively). Significant paravalvular leak (PL) was noted in 21 (13.1%)
patients immediately after TAVI and in 13 (9.6%) patients in follow-up (p <
0.001). Moderate or severe mitral regurgitation (msMR) was seen in 24 (14.9%)
patients from the initial group and in 19 (11.8%) patients after TAVI (p <
0.001). CONCLUSIONS: The TAVI had an immediate beneficial effect on LVEF, LV
walls thickness, and the incidence of msMR. The results of the procedure are
comparable with those described in other centres.
PMID- 25848371
TI - Hybrid stent implantation to the pulmonary artery from peripheral access via
recruited systemic-pulmonary shunt.
AB - The implantation of vascular stents in patients with low body weight and
difficult anatomy of the stenosis needs individual cannulation strategy or a
hybrid approach. We present a successful balloon angioplasty with direct stent
implantation to severe ostial stenosis of the left pulmonary artery to xenograft
anastomosis (LPA) in a 6-year-old boy late after surgical correction of pulmonary
atresia with ventricular septal defect. Peripheral approach to LPA was possible
after surgical rethoracotomy and the recruitment of a left Blalock-Taussig (BT)
shunt stump. The cooperation of cardiovascular intervention with surgical
approach appears a safe strategy for borderline patients referred for staged
treatment of complex congenital heart defects.
PMID- 25848372
TI - Stent loss in the radial artery - surgical vs. interventional approach - report
of two cases.
AB - Stent loss during coronary angioplasty is a complication that can be managed in
various manners; however, transradial access limits the options available. We
describe two coronary interventions complicated by stent dislodgement, initially
managed by pulling the stent back to the radial artery. Both stents were
unwillingly lost on different levels in radial arteries. The first case was
managed with a direct radial artery cut-down because distal location made it a
quick and straightforward procedure. In the second case a partially deployed
stent was lost in the proximal part of the radial artery. It was rewired,
deployed, and post-dilated with a larger balloon. This enabled continuation of
the procedure using the same access. Both cases were asymptomatic during 24
months of follow-up. It is crucial to avoid leaving artificial bodies in arteries
supplying vital organs because stent-related thrombosis or stenosis may seriously
compromise blood flow. Removing the stent via the introducer sheath should be
considered the optimal treatment. Unfortunately it is common that a partially
expanded stent will not pass through the sheath. The superficial location of the
distal radial artery segment facilitates surgical cut-down with local
anaesthesia. When dislodgement occurs in deeper segments of the radial artery,
the benefits from cut-down seem to be less because the procedure might take more
time and be more difficult - as in the presented case in which we decided to
rewire and fully expand the stent in situ. Retrieval of the stent at all costs
might have led to further complications; hence stent deployment may be a good
alternative to retrieval in such cases.
PMID- 25848373
TI - Transfemoral transcatheter aortic valve implantation in a patient with a severe
aortic stenosis and cardiogenic shock requiring intra-aortic balloon pump
support.
AB - The following paper presents a patient with severe aortic stenosis and severely
reduced left ventricular ejection fraction with intra-aortic balloon pump
counterpulsation support, who underwent transfemoral aortic valve implantation of
a CoreValve prosthesis.
PMID- 25848374
TI - Knuckle technique guided by intravascular ultrasound for in-stent restenosis
occlusion treatment.
AB - One of the rarest lesions is in-stent restenosis chronic total occlusion (CTO).
Limited data suggest that the treatment success rate is dependent on the
possibility to cross into the lumen of an occluded stent, and the decision about
what technique to use varies by operator preference. The knuckle technique is
used to create a deliberate dissection plane in various CTO techniques. A guide
wire is pushed until a complex loop is formed and advanced through the lesion. In
this report we present a case where a knuckle wire guided by intravascular
ultrasound control is used to penetrate the distal cap in an in-stent restenosis
CTO lesion.
PMID- 25848375
TI - Catheter inside the right heart for 22 years: to intervene or not to intervene?
AB - Treatment of a central venous catheter emboli that has been asymptomatic for a
number of years is controversial. A 56-year-old male patient who had an operation
for sinus Valsalva aneurism rupture 22 years ago was referred to cardiology
department for routine control. He had a mass inside the right heart on
echocardiographic examination, and computed tomography revealed that this mass
was an embolic piece of catheter. Catheters that have stayed inside the heart for
a long time are removed due to the risk of distal embolisation and endocarditis,
but the risk of removal is not known. Non-invasive follow-up of asymptomatic
patients is often preferred because of the stabilisation of the embolised
catheter due to endothelisation and the risk of complications during removal.
Treatment of patients with catheter-piece emboli who are asymptomatic should be
individualised, taking into account the risk of thrombosis, arrhythmia, and
infection.
PMID- 25848376
TI - Cutting balloon use may ease the optimal apposition of bioresorbable vascular
scaffold in in-stent stenosis.
AB - Bioresorbable vascular scaffolds (BVS) have different mechanical properties as
compared to metallic stents. Therefore, the standard procedural technique to
achieve appropriate deployment may differ. Utilisation of debulking techniques,
including cutting balloon and directional atherectomy prior to BVS deployment, is
still questionable. Herein, we discuss a case of coronary in-stent restenosis and
reveal the advantage of predilatation of the lesion with cutting balloon prior to
BVS deployment.
PMID- 25848377
TI - A unique case of systemic thromboembolism in a patient with arrhythmogenic right
ventricular cardiomyopathy.
AB - We report a case of a 37-year-old woman with arrhythmogenic right ventricular
cardiomyopathy (ARVC), after implantation of a cardioverter-defibrillator (ICD),
who was admitted to our hospital because of focal infarctions in the right kidney
and in the spleen. Echocardiography showed thrombi on the ICD electrode and the
presence of patent foramen ovale. Patent foramen ovale was successfully closed by
septal occluder. To our knowledge it is the first ever case report of paradoxical
thromboembolism in a patient with ARVC.
PMID- 25848378
TI - Left circumflex coronary artery occlusion due to a left atrial appendage closure
device.
AB - Nowadays, percutaneous left atrial appendage (LAA) closure is spreading, and a
large number of patients with this procedure have concomitant coronary artery
disease. With the presented case it could be concluded that coronary angiography
is recommended before LAA closure.
PMID- 25848379
TI - Emerging Intestinal Microsporidia Infection in HIV(+)/AIDS Patients in Iran:
Microscopic and Molecular Detection.
AB - BACKGROUND: Species of Microsporidia have been known as opportunistic obligate
intracellular parasites particularly in immunocompromised patients.
Enterocytozoon bieneusi is one of most prevalent intestinal microsporida
parasites in HIV(+)/AIDS patients. In this study, intestinal microsporidia
infection was determined in HIV(+)/AIDS patients using microscopic and molecular
methods. METHODS: Stool samples were collected from HIV(+)/AIDS patients during
12 months. All of the stool specimens washed with PBS (pH: 7.5). Slim slides were
prepared from each sample and were examined using light microscope with 1000X
magnification. DNA extraction carried out in microscopic positive samples. DNA
amplification and genus/species identification also performed by Nested-PCR and
sequencing techniques. RESULTS: From 81 stool samples, 25 were infected with
microsporidia species and E. bieneusi were identified in all of positive samples.
No Encephalitozoon spp. was identified in 81 collected samples using specific
primers. CONCLUSION: E. bieneusi is the most prevalent intestinal microsporidia
in immunocompromised patients of Iran. On the other hand, Nested-PCR using
specific primers for ssu rRNA gene is an appropriate molecular method for
identification of E. bieneusi.
PMID- 25848380
TI - An Analysis of Clinical Characteristics of Strongyloides stercoralis in 70
indigenous patients in Iran.
AB - BACKGROUND: Clinical manifestations of Strongyloides stercoralis are variable
from asymptomatic to hyperinfection and devastating disseminated infections.
Hereby, clinical characteristics of a large series of Iranian strongyloidiasis
indigenous cases are described. METHODS: The records of people referred to the
Helminthological Diagnostic Laboratory of School of Public Health, Tehran
University of Medical Sciences and School of Medicine, Gilan University of
Medical Sciences, during 2009-2013 were reviewed. For those patients that were
infected with S. stercoralis and their clinical manifestations and demographic
data were available (70 cases) a checklist was prepared and data analyzed.
RESULTS: Forty-three patients (61.4%) were male and 27 (38.6%) female.
Gastrointestinal, cutaneous and pulmonary symptoms were present in 71.4%, 25.7%,
and 15.7% of patients, respectively. None of them had larva currens eruption.
Eosinophilia was the most prevalent reason for suspicious on S. stercoralis, but
the mean was lower in elderly patients. Hyperinfection were recorded in 8
patients (11.4%), and 2 cases had disseminated infection. CONCLUSION:
Eosinophilia is common both in asymptomatic and symptomatic cases of
strongyloidiasis, but the mean tend to lower with increase in age.
PMID- 25848381
TI - Canine Babesiosis in China Caused by Babesia gibsoni: A Molecular Approach.
AB - BACKGROUND: To provide a point of reference to study the epidemiology and
clinical expression of canine babesiosis in China. METHODS: A total of 30 dogs
infected with canine babesiosis were evaluated by mean of clinical history,
physical examination, hematological, restriction fragment length polymorphism of
PCR products (PCR-RFLP) and sequencing analysis. RESULT: The most prevalent
clinical abnormalities were lethargy (100%), anorexia (100%), pale or icteric
mucous membranes (80%), fever (70%) and dark urine (70%). Hematology parameters
revealed that anemia and thrombocytopenia were the major abnormalities in blood
of dogs infected with canine babesia. The results of PCR-RFLP and sequencing
analysis indicated that B. gibsoni was the main species responsible for canine
babesiosis cases at the time of the study in Nanjing, China. CONCLUSIONS: The
results provide valuable information for better understanding of the epidemiology
of canine babesiosis in China.
PMID- 25848382
TI - Epidemiology, sero-diagnosis and therapeutic studies on nematodes infection in
balochi range-sheep at district quetta, balochistan, pakistan.
AB - BACKGROUND: Among the infectious organisms of parasitic origin, gastrointestinal
nematodes are very important as they have been reported worldwide. The main aim
of the present research study to highlight the annual epidemiological
contributing factors associated with the prevalence of gastrointestinal nematodes
and their control in sheep. METHODS: A total 1200 faecal samples (100 per month)
were collected from farmers holding Balochi-sheep (either sexes, 1-5 years old)
during January-December 2012 and analyzed to determine the prevalence of
nematodes based on microscopy and ELISA based diagnostic assay. Therapeutic
efficacies of different synthetic and herbal medicines against these nematodes
were assessed by field trials. RESULTS: Results showed that 23.92% Balochi-sheep
were infected with nematodes. Five nematodes infections were recorded with
highest prevalence of Haemonchus (7.75%) followed by Nematodirus (7.58%),
Strongyloides (4.42%), Trichostrongylus (2.33%) and Trichuris (1.83%). The
younger and older ewes (one and five years) presented higher nematodes prevalence
with peak during March/April and August/September. Haemonchus and Trichuris
positive samples based on coprological examination were also showed 92-100%
positive sensitivity for these nematodes by the ELISA. Sheep treated with
Ivermectin showed higher reduction (97.76%) in nematode egg counts followed by
Atreefal deedan (96.42%) and Oxfendazole (95.44%), respectively. CONCLUSION: The
gastro-intestinal nematodes are prevalent in all age and either sex of Balochi
sheep with peak during summer. The ELISA based diagnosis is more accurte. The
synthetic and herbal products are very effective against sheep nematodes.
PMID- 25848383
TI - Seroprevalence of Toxoplasma gondii Infections in Pregnant Women in Gorgan City,
Golestan Province, Northern Iran-2012.
AB - BACKGROUND: Toxoplasma gondii is one of the most prevalent parasites of human and
warm- blooded animals. Toxoplasmosis is important especially in two groups:
pregnant women and immunocompromised patients. If women acquire the primary
infection during the pregnancy, it would be life threatening or remains severe
disorders for the fetus. This study was performed to evaluate the seroprevalence
of T. gondii infection in pregnant women referred to Health Center in Gorgan
City, Golestan Province, northern Iran. METHODS: Serum samples were collected
from pregnant women referred to Health Center in Gorgan City, south eastern
Caspian Sea. Anti- Toxoplasma IgG and IgM antibodies were determined by
commercially ELISA kits and the relation of infection with socio-demographic and
risk factors such as age, education, occupation, cat ownership, soil contact and
some other factors was studied. RESULTS: From 555 tested sera of pregnant women
referred to Health Center in Gorgan, 39.8% had IgG antibodies against T. gondii
and 3.4% were positive for IgM antibodies. A significant correlation was seen
between T. gondii infection with age and soil contact. CONCLUSION: About 60% of
pregnant women in Gorgan City are seronegative against T. gondii, so they should
considered as at risk persons.
PMID- 25848384
TI - Paleoparasitological Findings from Rodent Coprolites Dated At 500 CE Sassanid Era
in Archeological Site of Chehrabad(Douzlakh), Salt Mine Northwestern Iran.
AB - BACKGROUND: In this paper, paleoparasitological findings from rodent excrements
obtained from Chehrabad Salt Mine archeological site located in northwest of Iran
are demonstrated and discussed. METHODS: Chehrabad Salt Mine archeological site
located in northwest of Iran, dated to the Achaemenid (mid 1(st) mill. BCE) and
to Sassanid (3(rd) cent. - 7(th) cent. CE) period, is a unique study area to
investigate parasites in the past millenniums in Iran. Rodent coprolites obtained
from this archeological site were thoroughly analyzed for parasite eggs using TSP
re-hydration technique. RESULTS: Specimen analyzed were attributed to juvenile
and adult rats based on their apparent morphology comparing with the modern dried
pellets of Muridea family. Helminth eggs retrieved from two positive pellets were
identified as Trichosomoides crassicauda, yphacia sp. and Trichuris sp.
CONCLUSION: The present paper discusses the first paleoparasitological findings
of rodent gastrointestinal helminthes in Iran along with possible favorite items
to rats in ancient Chehrabad Salt Mine.
PMID- 25848385
TI - Acanthamoeba species in Swimming Pools of Cairo, Egypt.
AB - BACKGROUND: The free-living amoebae Acanthamoeba spp. have been recognized as
etiologic agents of amoebic encephalitis, keratitis, otitis, lung lesions and
other skin infections mainly in immuno-compromised individuals. The purpose of
this study is to detect the presence of Acanthamoeba in swimming pools in Egypt
using a polymerase chain reaction (PCR) method. METHODS: Water samples were
collected from 10 different swimming pools in Cairo, Egypt. Samples were cultured
on non-nutrient agar for the detection of Acanthamoeba isolates that were
confirmed by PCR amplification using genus specific primers. The molecularly
confirmed Acanthamoeba isolates were morphologically identified to the species
level. RESULTS: Members of genus Acanthamoeba were detected in 49.2% of the
examined swimming-pool water samples. Morphologically, six Acanthamoeba species
were isolated from the examined swimming pool water namely A. polyphaga,
A.castellanii, A. rhysodes, A. mauritaniensis, A. royreba and A. triangularis.
All the identified species of Acanthamoeba were molecularly confirmed to be
related to the genus Acanthamoeba. CONCLUSION: The isolated species of
Acanthamoeba could provoke variable degrees of infections to the swimmers. The
culture method is cheaper and easier than PCR techniques that are faster for the
detection of free-living amoebae.
PMID- 25848386
TI - Triclabendazole (Anthelmintic Drug) Effects on the Excretory- Secretory Proteome
of Fasciola hepatica in Two Dimension Electrophoresis Gel.
AB - BACKGROUND: The aim of this study was to evaluate the protein spots of excretory
secretory products of Fasciola hepatica using two dimension electrophoresis
method in the presence and absence of triclabendazole drug which can be
considered to detect the target protein of the drug. METHODS: F. hepatica
parasites were collected from infected cattle livers, divided in two groups and
cultivated in RPMI 1640 medium. First group was treated with triclabendazole
(TCBZ) and second group considered as control. The excretory-secretory (ES)
products of each group were separated and total protein determined by Bradford
method. To provide proteome spots, the ES proteins were precipitated and two
dimension electrophoresis (2-DE) gel prepared. Protein amounts of two groups were
compared using the statistical t-test and protein spots from 2-DE in test and
control groups were also statistically analyzed. The protein spots of gels were
identified by using protein database. RESULTS: The t-test showed a significant
increase of total proteins in treated group (P<0.5). The protein spots count in
the control group was less than test group however statistically not significant
(p>0.05). Cathepsin L- protein (MW 36.7 pH 5.34), 14-3-3 epsilon 2 isoform (MW
28.2 pH 5.36), Cathepsin L1D (MW 36.5 pH 5.8) and Cathepsin L1D (MW 36.6 pH 6.26)
were identified in test group. CONCLUSION: It seems that, these results can be
considered to determine the proteins which the drug acts as a target on them.
PMID- 25848387
TI - Identification and Characterization of a Differentially Expressed Gene (07E12) in
the Infective Larvae of the Parasitic Nematode Ascaris suum.
AB - BACKGROUND: Parasitic nematodes cause animal and human diseases of major socio
economic importance worldwide. The suppression of parasite development at
particular developmental stages could provide an alternative approach for
nematode control. In this study, Ascaris suum was used as a model system in the
study of the differentially expressed genes in the infective L3 stage. METHODS:
The gene (07E12) was screened and identified from the subtractive cDNA library
for the infective larvae of Ascaris suum using real-time quantitative PCR. Then,
the full-length cDNA of 07E12 was characterized by 3' and 5' rapid amplification
of cDNA ends (RACE). The characteristics of the gene were further analyzed using
bioinformatic analyses. RESULTS: The results showed that the gene 07E12 was
differentially expressed in the third-stage larvae of A. suum and its expression
level in the infective larvae was much higher than in other stages. It was shown
that the gene 07E12 had 99% identity with the corresponding sequences of the A.
suum whole genome shotgun sequence containing the homologous sequences with
conserved sequences of Neuropeptide-Like Protein family member. Likewise, by
performing BLASTN and BLASTP searches in the GenBankTM, it was shown that this
gene had 99 % identity with A. suum cre-nlp-2 protein. CONCLUSION: This gene
07E12 which is differentially expressed in the third-stage larvae of A. suum may
encode a neuropeptide-like protein family member, a very important molecule in
the process of infecting a host.
PMID- 25848388
TI - Improved serodiagnosis of hydatid cyst disease using gold nanoparticle labeled
antigen B in naturally infected sheep.
AB - BACKGROUND: Cystic echinococcosis caused by the metacestode of Echinococcus
granulosus is a major problem in both humans and domestic animals health.
Therefore, a standardized and approachable diagnostic tool (rapid tests) for the
serodiagnosis of cystic echinococcosis (CE) is still needed. METHODS: In the
present work, antigen B labeled with gold nanoparticles was used to detect
antibodies against hydatid cyst disease. The prepared antigen B was analyzed by
SDS-PAGE. Tetra chloroauric acid (HAuCl4) was used to produce colloidal gold and
antigen B labeled by gold nanoparticles, then it was tested by using rabbits
antisera and sera from naturally infected sheep. The labeled antigen B was
evaluated using Dot-immunogold staining (Dot-IGS) method. RESULTS:
Electrophoretic pattern of hydatid cyst fluid showed the quality of bands in the
condensed fluid is better than crude fluid. SDS-PAGE analysis cyst fluid and
antigen B revealed three specific protein bands that were detected at molecular
weights of 24, 30 and 40 kDa that all are the subunits of antigen B. Evaluation
of antigen B labeled by gold nanoparticles by using Dot-IGS technique showed 1/1
and 1/50 dilutions in comparison with another has the best immunoreaction. In
this method, nanoparticles produced a typical purple color, when they binded to
the strip at the site of immunoreaction. CONCLUSION: Therefore, using gold
nanoparticles is a good candidate for detection of helminthiasis, also as
selective tools of early detection, simple and cost-effective, regardless of
specific skills and equipment with optimal durability.
PMID- 25848389
TI - Cryptosporidium infection in patients with gastroenteritis in sari, iran.
AB - BACKGROUND: Cryptosporidiosis is a common coccidian parasite infection in
patients with diarrhea that has worldwide distribution especially in developed
countries. Therefore, the aim of this study was to determine the occurrence of
Cryptosporidium infection in patients with gastroenteritis admitted to hospitals
of Mazandaran University of Medical Sciences by parasitological and molecular
methods in Sari, Iran. METHODS: Stool samples were collected from 348 patients
with gastroenteritis admitted to the hospitals of Medical University in the Sari
and Ghaemshahr cities in Mazandaran Province, Northern Iran in 2010-2011. Oocysts
of Cryptosporidium identified using Formalin-Ether concentration method and
stained by Aacid-fast staining (AFS) and Auramine phenol fluorescence (APF).
Genomic DAN extracted from microscopically positive samples and nested PCR -RFLP
by using SSU rRNA that identifies of the species of cryptosporidium. RESULTS: In
348 patients with gastroenteritis, the most clinical symptoms were diarrhea,
nausea, vomiting, dehydration, fever and weight loss. 2.3% (8 cases) of diarrheal
samples tested by both microscopy and molecular methods were positive for the
presence of cryptosporidium. Nested PCR products yielded unique bands of 846 bp,
correspond to cryptosporidium. Species diagnosis carried out by digesting the
secondary PCR product with SspI restriction enzyme, which noted 3 clearly bands
of 449, 254, and 108 bp correspond to Cryptosporidium spp. CONCLUSION: The
results of present study on Cryptosporidium spp. in this area can make a
background data for control programs and further molecular analyses. Thus,
further work needs to determine the origin of Cryptosporidium species in this
area.
PMID- 25848390
TI - Hydatid Cyst Surgeries in Patients Referred to Hospitals in East Azerbaijan
Province during 2009-2011.
AB - BACKGROUND: Hydatidosis, as the most important zoonotic parasitic disease in
Iran, has posed many health and economic losses. This study was conducted to
investigate the demographic characteristics of hydatid cyst surgeries in
hospitals of East Azerbaijan Province, Northwest of Iran. METHODS: Demographic
characteristics of all patients with hydatid cyst surgery in hospitals of the
province, during 2009-2011 were gathered including age, gender, occupation,
number and location of the cyst, clinical symptoms, place of residence and
history of contact with dog. They were extracted from reports of health center
and were analyzed using STATA 11 software. RESULTS: Out of 52 hydatid cyst
surgeries, 27 cases were females. Mean age of patients was 38.3 yr. Liver was
reported as the most involved organ. The most clinical symptoms were abdominal
and liver pain. Housewives comprised the most victims of the disease. Forty seven
percent of patients had one cyst and 59% had the history of contact with dog. The
majority of the patients were living in rural areas. CONCLUSION: Due to the high
costs of diagnosis and treatment of hydatidosis, collecting data on the
prevalence and transmission of the disease as well as on vulnerable groups seems
to be essential as the first step in controlling and preventing the disease.
PMID- 25848391
TI - Leishmaniasis in Turkey: Determination of Leishmania Species by Matrix-Assisted
Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS).
AB - BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in Southeastern Anatolia,
mainly in Sanliurfa and Hatay provinces, and the causative agents are mostly
Leishmania tropica and less frequently L. infantum. Here, we report the first
MALDI-TOF analyses of Leishmania promastigotes obtained from the cultures of two
CL cases from Osmaniye and Hatay provinces who were initially diagnosed by
microscopy, culture and identified as L. infantum with Real-Time PCR (RT-PCR).
METHODS: Samples obtained from the skin lesions of patients were initially
stained with Giemsa and cultivated in NNN medium. Examination of the smears and
cultures revealed Leishmania amastigotes and promastigotes, respectively. The
promastigotes (MHOM/TR/2012/CBU15 and MHOM/TR/2012/MK05) obtained from the
cultures of both patients were used for RT-PCR targeting the ITS-1 region in the
SSU of rRNA. The reference strains of four Leishmania species (L. infantum, L.
donovani, L. tropica and L. major) were initially assessed with MALDI-TOF and
their data were added to MALDI-TOF Biotyper Library. RESULTS: Both RT-PCR and
MALDI-TOF analyses indicated that the causative agent in both patient samples was
L. infantum. CONCLUSION: Despite disadvantages such as requirement of culture
fluid with nothing but promastigotes and high cost, MALDI-TOF analysis may be a
fast, sensitive and specific diagnostic tool in especially large-scale research
studies, where the cost declines, relatively.
PMID- 25848392
TI - An epidemiological survey of setaria in the abdominal cavities of Iranian sistani
and brahman cattle in the southeastern of iran.
AB - BACKGROUND: In this experiment, abdominal cavity of 518 Iranian Sistani cattle
and 498 Brahman cattle were inspected for the presence of Setaria spp. from April
2012 - May 2013. METHODS: The species were determined by microscopic examination
of the morphological characteristics of the anterior and posterior parts of the
parasites and authentic guidelines. RESULTS: The overall prevalence of Setaria
spp. was 28.6% and 36.5%, respectively and this difference was significant
(P<0.05). Out of 148 Sistani cattle which were infected with Setaria, 51(34.4%)
were infected with S. digitata, 31 (20.9%) were infected with S.
labiatopapillosa, 65 (43.9%) showed mixed infection of S. digitata and S.
labiatopapillosa and one case (0.6%) was infected with mixed infection of S.
labiatopapillosa, S. digitata and S. marshalli. These values were 87 (47.8%), 27
(14.8%), 67 (36.8%) and 1 (0.5%) for 182 infected Brahaman cows, respectively.
The proportion of infected cattle in spring and summer was greater than cooler
season (autumn and winter) significantly (P<0.001). The prevalence of infection
with Setaria in 2-3 years old Sistatni cattle (42.2 %) was greater than other age
categories (P<0.05). Furthermore, the infection rate between males (25.5%) and
females (37.3%) Iranian Sistani cattle showed significant difference (P =0.009).
CONCLUSION: It is important to point out the presence of cerebrospinal
setariosis, namely in sheep, goats and horses in the investigated area.
PMID- 25848393
TI - Isolation and identification of naegleria species from environmental water in
changchun, northeastern china.
AB - BACKGROUND: Naegleria is a free-living amoeba, and pathogenic Naegleria may pose
a health risk to people exposed to recreational water. Our objective in this
study was to determine if there are pathogenic amoebae in environmental water
samples from Changchun, Northeastern China. METHODS: During July to September
2012, a total of 70 water samples were collected from Changchun, Northeastern
China, and Naegleria was enriched by in vitro culture and detected by PCR using
Naegleria genus-specific primers. Resulting PCR products were sequenced and
phylogenetically analyzed to identify Naegleria species. RESULTS: Naegleria was
detected in 65 (92.9%) of 70 water samples. DNA sequence and phylogenetic
analyses based on the internal transcribed spacer (ITS) rDNA sequences revealed
four Naegleria species, including N. pagei (n = 24) and N. Australiensis (n =
18), N. clarki (n = 13) and N. gruberi (n = 10), in which N. australiensis is
pathogenic to mice. But the pathogenic species N. fowleri was not detected.
CONCLUSION: This is the first report on Naegleria species in Northeastern China,
showing that almost all environmental water samples were contaminated with
Naegleria, including N. pagei, N. Australiensis, N. clarki and N. gruberi, which
should be considered a potential public health threat.
PMID- 25848394
TI - Integrating Morphology, Breeding Ground and Mitochondrial COI Gene Analysis for
Species Identification of Bellamya lithophaga (Gastropoda: Viviparidae) in China.
AB - BACKGROUND: Angiostrongylus cantonensis is a zoonotic public health concern that
causes human severe eosinophilic meningitis in Southeast Asia and China. As a
medically important intermediate host of A. cantonensis, Bellamya lithophaga
(Gastropoda: Viviparidae) is often confused with other morphologically similar
sibling species of genus Bellamya, such as B. aeruginosa and B. purificata in the
past. Hence, the aim of the present study was to investigate evidences to
discriminate these equivocal Bellamya species. METHODS: This study was carried
out by getting Bellamya snail samples from Fujian Province in the South-East of
China. The snail morphological features, breeding grounds and phylogenetic
relationship according to mitochondrial cytochrome c oxidase subunit I (COI) gene
marker were analyzed. RESULTS: Based on external morphology, radular shape and
cusp formula, as well as major breeding environment, B. lithophaga could be
distinguished from B. aeruginosa, B. purificata. The phylogenetic tree also
unconfirmed that B. lithophaga belongs to a different genetic clade from other
morphologically similar species. CONCLUSION: Our findings demonstrate the
significant differences in B. lithophaga and other sibling species, which
supports the traditional species delimitation in the genus Bellamya.
PMID- 25848395
TI - A Histopathology Study of Caspian Seal (Pusa caspica) (Phocidae, Mammalia) Liver
Infected with Trematode, Pseudamphistomum truncatum (Rudolphi, 1819)
(Opisthorchidae, Trematoda).
AB - BACKGROUND: Main objective of this study was to investigate the invasive activity
of the liver fluke, Pseudamphistomom truncatum against the Caspian seal (Pusa
caspica) and was exemplified at the gross, light microscopy (LM) and electron
microscopy (EM) levels. METHODS: The study was done on a freshly dead Caspian
Seal in the southern coast of Caspian Sea. The checked Caspian seal probably
being died of canine distemper virus and was found host to numerous parasites of
four helminth species. RESULTS: P. truncatum caused edematous foci on the surface
of the liver with prominent fluid accumulation. Sections of the liver viewed with
LM had multiple necrotic areas with extensive hemorrhaging and disorganized
hepatic lobules. Granulocytes and invasion of connective tissue were prominent.
Whole worms were visible with invasive pathways through the host tissue. Damage
to both hepatic ducts and blood vessels were prominent. At the EM level,
organelles within the impacted hepatocytes were disorganized as exemplified by
the cristae of the mitochondria and the endoplasmic reticulum. Parasite eggs were
scattered throughout the tissue. CONCLUSION: It was shown that this trematode can
be very pathogenic to Caspian Seal and as this only mammal of Caspian Sea is an
endangered species; this needs more investigation toward control or possible
treatment of this helminth.
PMID- 25848396
TI - Epidemiological study of gastrointestinal helminthes of canids in chaharmahal and
bakhtiari province of iran.
AB - BACKGROUND: The present study was carried out to describe the epidemiological
aspects of gastrointestinal helminthic infections of canids in Chaharmahal and
Bakhtiari Province, the central western part of Iran. METHODS: Forty nine canid
species including, dogs, jackals, foxes and wolves were included in this study.
The contents of their alimentary canal were inspected in order to isolate and
identify the parasitic helminthes of this system. To identify the worms, the
Soulsbey and Anderson identification key and light microscopy were used. RESULTS:
Based on necropsy findings, 35 (71.4%) of examined animals were infected with at
least one helminth. The prevalence of identified worms was as follows:
Mesocestoides lineatus (55.1%), Joyeuxiella echinorinchoides (26.5%), Taenia
hydatigena (12.2%), T. multiceps (8.2%), T. ovis (2%), Dipylidium caninum (2%)
and Spirura spp. (2%). No significant difference was noticed between the sampling
areas, age and helminth infection. Only a significant difference was observed for
prevalence of T. multiceps in wolf (25%), dog (21.4%), jackal and fox (0%),
respectively (P < 0.05). CONCLUSION: The canids in Chaharmahal and Bakhtiari
harbor several parasites that some kind of them have zoonotic importance and may
pose a threat to community health specially in rural areas.
PMID- 25848397
TI - Human Linguatulosis Caused by Linguatula serrata in the City of Kerman, South
eastern Iran- Case Report.
AB - Human linguatulosis poses an important medical and veterinary concern in endemic
countries. Animals, as reservoir host, play a major role in transmission of
infestation and epidemiology of the disease. This study reports a case of human
linguatulosis caused by Linguatula serrata in the city of Kerman, South-eastern
Iran. A woman suffering from upper respiratory symptoms is presented. The patient
consumed raw liver of sheep who was admitted to the Afzalipour University
Hospital in Kerman for the symptoms of upper respiratory tract. In microscopic
examination of the nasopharyngeal discharge, L. serrata was detected. This report
has future medical implication in precise diagnosis of L. serrata in patients
with complaints of nasopharyngeal symptoms.
PMID- 25848398
TI - First Molecular Identification of Sarcocystis ovicanis (Protozoa, Apicomplexa) in
the Brain of Sheep in Iran.
AB - BACKGROUND: The objective of the present study was to survey the presence of
Sarcocystis in sheep's brain in North Khorasan Province. METHODS: In general, 80
samples of sheep's brain were collected from slaughtered sheep in slaughterhouses
of North Khorasan Province. Tissue digestion method was used for observing
bradyzoites in tissues. Histopathological processing tracing Sarcocystis and
ensuing structural change in the brain tissue were conducted. PCR analysis was
conducted on all the brain samples. Sequencing was done for one PCR product.
Genotype was identified by Blast search and homology analysis. RESULT:
Sarcocystis spp. was found in one of the brain samples (1.25%) using tissue
digestion method. The presence of bradyzoite was also confirmed in the prepared
histopathological sections. PCR analysis was positive in one of samples.
Genotyping of one sample proved that Sarcocystis species was Sarcocystis ovicanis
and the nucleotide sequence of this parasite was deposited in the GenBank
database under accession number No.KF489431. CONCLUSION: Sarcocystis ovicanis can
involve brain tissue of sheep and consequently causes clinical symptoms.
PMID- 25848399
TI - Mouse models of mastitis - how physiological are they?
AB - Lactation mastitis is a common, but poorly understood, inflammatory breast
disease that is a significant health burden. A better understanding of the
aetiology of mastitis is urgently required, and will assist in the development of
improved prevention and treatment strategies in both human and animal species.
Studies in mice have the potential to greatly assist in identifying new drug
candidates for clinical trials, and in developing a better understanding of the
disease. Mouse models of mastitis involve administration of a mastitis-inducing
agent to the mammary gland usually during lactation to examine the host immune
response, and progression through to resolution of the disease. There are
important variations in the protocols of these mouse models that critically
affect the conclusions that can be drawn from the research. Some protocols
involve weaning of offspring at the time of mastitis induction, and there are
variations in the mastitis-inducing agent and its carrier. Induction of mammary
gland involution through weaning of offspring limits the capacity to study the
disease in the context of a lactating mammary gland. Administration of live
bacteria in an aqueous carrier can cause sepsis, restricting the physiological
relevance of the model. Mouse model research should employ appropriately designed
controls and closely monitor the health of the mice. In this commentary, we
discuss the advantages and study design limitations of each mouse model, and
highlight the potential for further development of physiologically relevant mouse
models of mastitis.
PMID- 25848400
TI - The relationship of weight change trajectory with medial temporal lobe atrophy in
patients with mild Alzheimer's disease: results from a cohort study.
AB - INTRODUCTION: Weight loss has been described in 20% to 45% of patients with
Alzheimer's disease (AD) and has been associated with adverse outcomes. Various
mechanisms for weight loss in AD patients have been proposed, though none has
been proven. This study aimed to elucidate a mechanism of weight loss in AD
patients by examining the hypothesis that weight loss is associated with medial
temporal lobe atrophy (MTA). METHODS: Patients from the Frisian Alzheimer's
disease cohort study (a retrospective, longitudinal study of 576 community
dwelling AD patients) were included when a brain MRI was performed on which MTA
could be assessed. To investigate the hypothesis that weight loss is associated
with MTA, we investigated whether the trajectory of body weight change depends on
the severity of MTA at the time of diagnosis (that is baseline). We hypothesized
that patients with more severe MTA at baseline would have a lower body weight at
baseline and a faster decrease in body weight during the course of the disease.
The generalized linear mixed model (GLMM) was used to determine the relationship
of weight change trajectory with MTA severity. RESULTS: In total, 214 patients
(median age 79 years, median MMSE 23, mean weight 73.9 kg) were included.
Patients with moderate, severe or very severe MTA at baseline weighed 3.2 to 6.8
kg more than patients with no or mild MTA. During the 3.5 years, patients gained
on average 1.7 kg in body weight, irrespective of the severity of their MTA at
baseline. CONCLUSIONS: We found no evidence that MTA is associated with weight
loss in AD patients. Moreover, contrary to what was expected, AD patients did not
lose but gained weight during follow-up.
PMID- 25848402
TI - Synergy of drug combinations in treating multidrug-resistant Pseudomonas
aeruginosa.
AB - BACKGROUND: With the emergence of metallo-betalactamases (MBL) in Pseudomonas
aeruginosa (P. aeruginosa), the value of carbapenem, the drug of last resort, is
being severely compromised. Curtailing the use of carbapenems becomes paramount
if resistance is to be reined in. AIMS: To study the role of synergy between
combinations of drugs as an alternative treatment choice for P. aeruginosa.
Synergy was studied between combinations of levofloxacin with piperacillin
tazobactam and levofloxacin with cefoperazone-sulbactam by time-kill and
chequerboard techniques. METHODS: P. aeruginosa were tested for antibiotic
susceptibility by the disc diffusion assay (260 isolates) and E-test (60
isolates). Synergy testing by chequerboard and time-kill assays was performed
with combinations of piperacillin-tazobactam with levofloxacin (11 isolates) and
cefoperazone-sulbactam with levofloxacin (10 isolates). RESULTS: Nearly all
isolates were susceptible to piperacillin-tazobactam (96.1 per cent), followed by
piperacillin (78.5 per cent). Seventy-one isolates (27.3 per cent) were found to
be multidrug resistant and 19.6 per cent were ESBL producers. MIC50 of amikacin
was 32MUg/ml and MIC90 was 64MUg/ml. MIC50 and MIC90 of cefoperazone-sulbactam
was 32MUg/ml and 64MUg/ml, and for levofloxacin it was 10MUg/ml and 240MUg/ml,
respectively. Piperacillin-tazobactam had MIC50 and MIC90 of 5MUg/ml and
10MUg/ml, respectively. Synergy was noted in 72.7 per cent isolates for
levofloxacin and piperacillin-tazobactam combination, the remaining 27.3 per cent
isolates showed addition by both chequerboard and time-kill assay. For
levofloxacin and cefoperazone-sulbactam, only 30 per cent isolates had synergy,
40 per cent showed addition, 20 per cent indifference, and 10 per cent were
antagonistic by the chequerboard method. CONCLUSION: The combination of
levofloxacin and piperacillin-tazobactam is a good choice for treatment of such
strains.
PMID- 25848401
TI - HIV effects on age-associated neurocognitive dysfunction: premature cognitive
aging or neurodegenerative disease?
AB - Marked improvements in survival and health outcome for people infected with HIV
have occurred since the advent of combination antiretroviral therapy over a
decade ago. Yet HIV-associated neurocognitive disorders continue to occur with an
alarming prevalence. This may reflect the fact that infected people are now
living longer with chronic infection. There is mounting evidence that HIV
exacerbates age-associated cognitive decline. Many middle-aged HIV-infected
people are experiencing cognitive decline similar that to that found among much
older adults. An increased prevalence of vascular and metabolic comorbidities has
also been observed and is greatest among older adults with HIV. Premature age
associated neurocognitive decline appears to be related to structural and
functional brain changes on neuroimaging, and of particular concern is the fact
that pathology indicative of neurodegenerative disease has been shown to occur in
the brains of HIV-infected people. Yet notable differences also exist between the
clinical presentation and brain disturbances occurring with HIV and those
occurring in neurodegenerative conditions such as Alzheimer's disease. HIV
interacts with the aging brain to affect neurological structure and function.
However, whether this interaction directly affects neurodegenerative processes,
accelerates normal cognitive aging, or contributes to a worsening of other
comorbidities that affect the brain in older adults remains an open question.
Evidence for and against each of these possibilities is reviewed.
PMID- 25848403
TI - Percutaneous aspiration versus catheter drainage of liver abscess: A
retrospective review.
AB - BACKGROUND: A review of the effectiveness and outcomes in liver abscess drainage
performed by different operators using percutaneous aspiration (PA) and catheter
drainage (PCD), respectively, from 2008-2013 at Sir Charles Gairdner Hospital, a
tertiary hospital in Australia. METHODS: Forty-two patients (29 males and 13
females; aged between 28-93 years; median age of 67 years) with liver abscesses
underwent either ultrasound or CT-guided PA (n=22) and PCD (n=20) in conjunction
with appropriate antimicrobial therapy. A median of 18 Gauge needle and 10 French
catheters were utilised. RESULTS: Nineteen (86.4 per cent) PA cases and 12 (60
per cent) PCD cases were successfully drained on a single attempt (p=0.08). More
male patients (69 per cent) than females (31 per cent) were observed. Portal
sepsis (42.9 per cent) was the most common cause identified. Fever (47.6 per
cent) was the most frequent clinical presentation on admission. Thirty-two
patients (76.2 per cent) had solitary abscesses with a right lobe (59.5 per cent)
predilection. CRP was significantly raised. The PCD group observed a
significantly larger abscess size (p=0.01). Klebsiella pneumoniae was the most
common organism isolated in both pus (33.3 per cent) and blood cultures (11.9 per
cent). Five procedure-related complications were noted, all in the PCD group.
Thirty-day mortality was 2.4 per cent. No difference was observed in clinical and
treatment outcomes in both groups. CONCLUSION: The null hypothesis that both PA
and PCD are equally effective in the drainage of liver abscess cannot be
rejected. Apart from PA being simpler and safer to perform, the higher incidence
of indwelling catheter-associated complications suggests that a trial of PA
should always be attempted first.
PMID- 25848404
TI - Selective myelosuppression following yellow phosphorus ingestion.
AB - Toxicity from accidental and intentional ingestion of yellow phosphorus,
ubiquitously present in fireworks and rodenticides, has recently become more
frequent. Gastrointestinal, renal, neurologic, and cardiovascular manifestations
are common, with mortality of 23 per cent to 73 per cent. Reports of
haematological abnormalities are rare. We report only the second case of severe
neutropenia secondary to selective myelosuppression in a 14-year-old girl
following intentional ingestion of yellow phosphorus. Leucocyte counts recovered
spontaneously without further complications. Our case indicates that, besides
hepatic and renal function monitoring, physicians should meticulously monitor
blood counts in such cases for early detection of marrow suppression. Further
studies are required to elucidate the complex mechanisms and significance of this
unusual toxicity of yellow phosphorus.
PMID- 25848405
TI - A unique case of bilateral sciatic nerve variation within the gluteal compartment
and associated clinical ramifications.
AB - An abnormal course of a nerve either through or around a muscle may yield
multiple or anomalous muscle innervation. Further, if nerves are inappropriately
trapped within the confines of a muscle or irregular boundaries, variant
emergence of a nerve could give rise to symptoms of an entrapment neuropathy.
Upon routine dissection in the Department of Anatomy at the American University
of Antigua College of Medicine, bilateral variants in the emergence of the
sciatic nerve from the pelvis to the gluteal compartment were discovered in an
elderly adult female cadaver. In the left gluteal compartment, the sciatic nerve
had a high division where the peroneal division exited the pelvis superior to the
piriformis muscle while the tibial division exited inferior to the piriformis. In
the right gluteal compartment, the peroneal division was observed to have exited
the pelvis between a split piriformis muscle before it joined the tibial division
of the sciatic nerve. Knowledge of such variations in the course of the sciatic
nerve may improve diagnosis and treatment of pathologies in this region.
PMID- 25848406
TI - Should Australia consider opt-out HIV testing?
PMID- 25848407
TI - N-Cadherin-Mediated Signaling Regulates Cell Phenotype for Nucleus Pulposus Cells
of the Intervertebral Disc.
AB - Juvenile nucleus pulposus (NP) cells of the intervertebral disc (IVD) are large,
vacuolated cells that form cell clusters with strong cell-cell interactions. With
maturation and aging, NP cells lose their ability to form these cell clusters,
with aging-associated changes in NP cell phenotype, morphology, and proteoglycan
synthesis that may contribute to IVD degeneration. Therefore, it is important to
understand the mechanisms governing juvenile NP cell cluster behavior towards the
goal of revealing factors that can promote juvenile, healthy NP cell phenotypes.
N-cadherin has been identified as a cell-cell adhesion marker that is present in
juvenile NP cells, but disappears with age. The goal of this study was to reveal
the importance of N-cadherin in regulating cell-cell interactions in juvenile NP
cell cluster formation and test for a regulatory role in maintaining a juvenile
NP phenotype in vitro. Juvenile porcine IVD cells, of notochordal origin, were
promoted to form cell clusters in vitro, and analyzed for preservation of the
juvenile NP phenotype. Additionally, cadherin-blocking experiments were performed
to prevent cluster formation in order to study the importance of cluster
formation in NP cell signaling. Findings reveal N-cadherin-mediated cell-cell
contacts promote cell clustering behavior and regulate NP cell matrix production
and preservation of NP-specific markers. Inhibition of N-cadherin-mediated
contacts resulted in loss of all features of the juvenile NP cell. These results
establish a regulatory role for N-cadherin in juvenile NP cells, and suggest that
preservation of the N-cadherin mediated cell-cell contact is important for
preserving juvenile NP cell phenotype and morphology.
PMID- 25848408
TI - Testing a Moderated Mediation Model of Mindfulness, Psychosocial Stress, and
Alcohol Use among African American Smokers.
AB - Mindfulness-based strategies have received empirical support for improving coping
with stress and reducing alcohol use. The present study presents a moderated
mediation model to explain how mindfulness might promote healthier drinking
patterns. This model posits that mindfulness reduces perceived stress, leading to
less alcohol use, and also weakens the linkage between stress and alcohol use.
African American smokers (N = 399, 51% female, Mage = 42) completed measures of
dispositional mindfulness, perceived stress, quantity of alcohol use, frequency
of binge drinking, and alcohol use disorder symptoms. Participants with higher
levels of dispositional mindfulness reported less psychosocial stress and lower
alcohol use on all measures. Furthermore, mindfulness moderated the relationship
between perceived stress and quantity of alcohol consumption. Specifically,
higher perceived stress was associated with increased alcohol use among
participants low, but not high, in mindfulness. Mindfulness may be one strategy
to reduce perceived stress and associated alcohol use among African American
smokers.
PMID- 25848410
TI - Legal and regulatory considerations associated with use of patient-generated
health data from social media and mobile health (mHealth) devices.
AB - Patient-generated health data are coming into broader use across the health care
spectrum and hold great promise as a means to improve care and health outcomes.
At the same time, rapid evolution in the social media and mobile health (mHealth)
market has promoted an environment in which creation and transmission of personal
health information is easy, quick, and appealing to patients. However, adoption
of social media and mHealth by providers is hampered by legal and regulatory
concerns with regard to data ownership and data use. This article defines common
forms of patient-generated health data (PGHD) and describes how PGHD is used in
clinical settings. It explores issues related to protection of personal health
information, including that of children and adolescents, data security, and other
potential barriers such as physician licensure. It also discusses regulatory and
legal considerations providers and patients should consider before using social
media and mobile health apps.
PMID- 25848409
TI - Leveraging electronic tablets for general pediatric care: a pilot study.
AB - BACKGROUND: We have previously shown that a scan-able paper based interface
linked to a computerized clinical decision support system (CDSS) can effectively
screen patients in pediatric waiting rooms and support the physician using
evidence based care guidelines at the time of clinical encounter. However, the
use of scan-able paper based interface has many inherent limitations including
lacking real time communication with the CDSS and being prone to human and system
errors. An electronic tablet based user interface can not only overcome these
limitations, but may also support advanced functionality for clinical and
research use. However, use of such devices for pediatric care is not well studied
in clinical settings. OBJECTIVE: In this pilot study, we enhance our pediatric
CDSS with an electronic tablet based user interface and evaluate it for usability
as well as for changes in patient questionnaire completion rates. METHODS: Child
Health Improvement through Computers Leveraging Electronic Tablets or CHICLET is
an electronic tablet based user interface. It is developed to augment the
existing scan-able paper interface to our CDSS. For the purposes of this study,
we deployed CHICLET in one outpatient pediatric clinic. Usability factors for
CHICLET were evaluated via caregiver and staff surveys. RESULTS: When compared to
the scan-able paper based interface, we observed an 18% increase or 30% relative
increase in question completion rates using CHICLET. This difference was
statistically significant. Caregivers and staff survey results were positive for
using CHICLET in clinical environment. CONCLUSIONS: Electronic tablets are a
viable interface for capturing patient self-report in pediatric waiting rooms. We
further hypothesize that the use of electronic tablet based interfaces will drive
advances in computerized clinical decision support and create opportunities for
patient engagement.
PMID- 25848411
TI - Emergency medicine resident physicians' perceptions of electronic documentation
and workflow: a mixed methods study.
AB - OBJECTIVE: To understand emergency department (ED) physicians' use of electronic
documentation in order to identify usability and workflow considerations for the
design of future ED information system (EDIS) physician documentation modules.
METHODS: We invited emergency medicine resident physicians to participate in a
mixed methods study using task analysis and qualitative interviews. Participants
completed a simulated, standardized patient encounter in a medical simulation
center while documenting in the test environment of a currently used EDIS. We
recorded the time on task, type and sequence of tasks performed by the
participants (including tasks performed in parallel). We then conducted semi
structured interviews with each participant. We analyzed these qualitative data
using the constant comparative method to generate themes. RESULTS: Eight resident
physicians participated. The simulation session averaged 17 minutes and
participants spent 11 minutes on average on tasks that included electronic
documentation. Participants performed tasks in parallel, such as history taking
and electronic documentation. Five of the 8 participants performed a similar
workflow sequence during the first part of the session while the remaining three
used different workflows. Three themes characterize electronic documentation: (1)
physicians report that location and timing of documentation varies based on
patient acuity and workload, (2) physicians report a need for features that
support improved efficiency; and (3) physicians like viewing available patient
data but struggle with integration of the EDIS with other information sources.
CONCLUSION: We confirmed that physicians spend much of their time on
documentation (65%) during an ED patient visit. Further, we found that resident
physicians did not all use the same workflow and approach even when presented
with an identical standardized patient scenario. Future EHR design should
consider these varied workflows while trying to optimize efficiency, such as
improving integration of clinical data. These findings should be tested
quantitatively in a larger, representative study.
PMID- 25848412
TI - Association between electronic health records and health care utilization.
AB - BACKGROUND: The federal government is investing approximately $20 billion in
electronic health records (EHRs), in part to address escalating health care
costs. However, empirical evidence that provider use of EHRs decreases health
care costs is limited. OBJECTIVE: To determine any association between EHRs and
health care utilization. METHODS: We conducted a cohort study (2008-2009) in the
Hudson Valley, a multi-payer, multiprovider community in New York State. We
included 328 primary care physicians in predominantly small practices (median
practice size four primary care physicians), who were caring for 223,772
patients. Data from an independent practice association was used to determine
adoption of EHRs. Claims data aggregated across five commercial health plans was
used to characterize seven types of health care utilization: primary care visits,
specialist visits, radiology tests, laboratory tests, emergency department
visits, hospital admissions, and readmissions. We used negative binomial
regression to determine associations between EHR adoption and each utilization
outcome, adjusting for ten physician characteristics. RESULTS: Approximately half
(48%) of the physicians were using paper records and half (52%) were using EHRs.
For every 100 patients seen by physicians using EHRs, there were 14 fewer
specialist visits (adjusted p < 0.01) and 9 fewer radiology tests (adjusted p =
0.01). There were no significant differences in rates of primary care visits,
laboratory tests, emergency department visits, hospitalizations or readmissions.
CONCLUSIONS: Patients of primary care providers who used EHRs were less likely to
have specialist visits and radiology tests than patients of primary care
providers who did not use EHRs.
PMID- 25848413
TI - CorRECTreatment: a web-based decision support tool for rectal cancer treatment
that uses the analytic hierarchy process and decision tree.
AB - BACKGROUND: The selection of appropriate rectal cancer treatment is a complex
multi-criteria decision making process, in which clinical decision support
systems might be used to assist and enrich physicians' decision making.
OBJECTIVE: The objective of the study was to develop a web-based clinical
decision support tool for physicians in the selection of potentially beneficial
treatment options for patients with rectal cancer. METHODS: The updated decision
model contained 8 and 10 criteria in the first and second steps respectively. The
decision support model, developed in our previous study by combining the Analytic
Hierarchy Process (AHP) method which determines the priority of criteria and
decision tree that formed using these priorities, was updated and applied to 388
patients data collected retrospectively. Later, a web-based decision support tool
named corRECTreatment was developed. The compatibility of the treatment
recommendations by the expert opinion and the decision support tool was examined
for its consistency. Two surgeons were requested to recommend a treatment and an
overall survival value for the treatment among 20 different cases that we
selected and turned into a scenario among the most common and rare treatment
options in the patient data set. RESULTS: In the AHP analyses of the criteria, it
was found that the matrices, generated for both decision steps, were consistent
(consistency ratio<0.1). Depending on the decisions of experts, the consistency
value for the most frequent cases was found to be 80% for the first decision step
and 100% for the second decision step. Similarly, for rare cases consistency was
50% for the first decision step and 80% for the second decision step.
CONCLUSIONS: The decision model and corRECTreatment, developed by applying these
on real patient data, are expected to provide potential users with decision
support in rectal cancer treatment processes and facilitate them in making
projections about treatment options.
PMID- 25848414
TI - The value of clinical teachers for EMR implementations and conversions.
AB - Effective physician training is an essential aspect of EMR implementation.
However, it can be challenging to find instructors who can present the material
in a clinically relevant manner. The authors describe a unique physician-training
program, utilizing medical students as course instructors. This approach resulted
in high learner satisfaction rates and provided significant cost-savings compared
to alternative options.
PMID- 25848415
TI - Successful physician training program for large scale EMR implementation.
AB - End-user training is an essential element of electronic medical record (EMR)
implementation and frequently suffers from minimal institutional investment. In
addition, discussion of successful EMR training programs for physicians is
limited in the literature. The authors describe a successful physician-training
program at Stanford Children's Health as part of a large scale EMR
implementation. Evaluations of classroom training, obtained at the conclusion of
each class, revealed high physician satisfaction with the program. Free-text
comments from learners focused on duration and timing of training, the learning
environment, quality of the instructors, and specificity of training to their
role or department. Based upon participant feedback and institutional experience,
best practice recommendations, including physician engagement, curricular design,
and assessment of proficiency and recognition, are suggested for future provider
EMR training programs. The authors strongly recommend the creation of coursework
to group providers by common workflow.
PMID- 25848416
TI - Data collection methods in health services research: hospital length of stay and
discharge destination.
AB - BACKGROUND: Hospital length of stay and discharge destination are important
outcome measures in evaluating effectiveness and efficiency of health services.
Although hospital administrative data are readily used as a data collection
source in health services research, no research has assessed this data collection
method against other commonly used methods. OBJECTIVE: Determine if
administrative data from electronic patient management programs are an effective
data collection method for key hospital outcome measures when compared with
alternative hospital data collection methods. METHOD: Prospective observational
study comparing the completeness of data capture and level of agreement between
three data collection methods; manual data collection from ward-based sources,
administrative data from an electronic patient management program (i.PM), and
inpatient medical record review (gold standard) for hospital length of stay and
discharge destination. RESULTS: Manual data collection from ward-based sources
captured only 376 (69%) of the 542 inpatient episodes captured from the hospital
administrative electronic patient management program. Administrative data from
the electronic patient management program had the highest levels of agreement
with inpatient medical record review for both length of stay (93.4%) and
discharge destination (91%) data. CONCLUSION: This is the first paper to
demonstrate differences between data collection methods for hospital length of
stay and discharge destination. Administrative data from an electronic patient
management program showed the highest level of completeness of capture and level
of agreement with the gold standard of inpatient medical record review for both
length of stay and discharge destination, and therefore may be an acceptable data
collection method for these measures.
PMID- 25848417
TI - A national survey of parent perspectives on use of patient portals for their
children's health care.
AB - OBJECTIVES: To assess parents' current utilization and future willingness to use
patient portals to interact with their child's health care provider. METHODS: A
cross-sectional survey of a nationally representative sample of US parents was
conducted using an established online panel. Bivariate analyses assessed
associations between current utilization and future willingness to use patient
portals, parental concerns, and demographic variables. RESULTS: Among the 1,420
parent respondents, 40% did not know whether their child's health practice offers
the option of setting up a patient portal for their child. Of the 21% of parents
who reported being offered the option of setting up a patient portal for their
child, 59% had done so. Among parents who had the option but chose not to set up
a patient portal for their child, lack of time and low perceived need were the
main reasons cited. Current use and likelihood of future use was highest for
viewing lab results and immunization records. The most common concern about
patient portals was the security of the child portal system. CONCLUSIONS: Current
use of patient portals by parents is low. Only about half of parents currently
using or likely to use a portal perceive value in using portals for certain
tasks, which suggests that providers will need to continue traditional
communication mechanisms to reach their entire patient population.
PMID- 25848419
TI - Electronic health records and patient safety: co-occurrence of early EHR
implementation with patient safety practices in primary care settings.
AB - BACKGROUND: The role of electronic health records (EHR) in enhancing patient
safety, while substantiated in many studies, is still debated. OBJECTIVE: This
paper examines early EHR adopters in primary care to understand the extent to
which EHR implementation is associated with the workflows, policies and practices
that promote patient safety, as compared to practices with paper records. Early
adoption is defined as those who were using EHR prior to implementation of the
Meaningful Use program. METHODS: We utilized the Physician Practice Patient
Safety Assessment (PPPSA) to compare primary care practices with fully
implemented EHR to those utilizing paper records. The PPPSA measures the extent
of adoption of patient safety practices in the domains: medication management,
handoffs and transition, personnel qualifications and competencies, practice
management and culture, and patient communication. RESULTS: Data from 209 primary
care practices responding between 2006-2010 were included in the analysis: 117
practices used paper medical records and 92 used an EHR. Results showed that,
within all domains, EHR settings showed significantly higher rates of having
workflows, policies and practices that promote patient safety than paper record
settings. While these results were expected in the area of medication management,
EHR use was also associated with adoption of patient safety practices in areas in
which the researchers had no a priori expectations of association. CONCLUSIONS:
Sociotechnical models of EHR use point to complex interactions between technology
and other aspects of the environment related to human resources, workflow,
policy, culture, among others. This study identifies that among primary care
practices in the national PPPSA database, having an EHR was strongly empirically
associated with the workflow, policy, communication and cultural practices
recommended for safe patient care in ambulatory settings.
PMID- 25848418
TI - Use of computer decision support in an antimicrobial stewardship program (ASP).
AB - OBJECTIVE: Document information needs, gaps within the current electronic
applications and reports, and workflow interruptions requiring manual information
searches that decreased the ability of our antimicrobial stewardship program
(ASP) at Intermountain Healthcare (IH) to prospectively audit and provide
feedback to clinicians to improve antimicrobial use. METHODS: A framework was
used to provide access to patient information contained in the electronic medical
record, the enterprise-wide data warehouse, the data-driven alert file and the
enterprise-wide encounter file to generate alerts and reports via pagers, emails
and through the Centers for Diseases and Control's National Healthcare
Surveillance Network. RESULTS: Four new applications were developed and used by
ASPs at Intermountain Medical Center (IMC) and Primary Children's Hospital (PCH)
based on the design and input from the pharmacists and infectious diseases
physicians and the new Center for Diseases Control and Prevention/National
Healthcare Safety Network (NHSN) antibiotic utilization specifications. Data from
IMC and PCH now show a general decrease in the use of drugs initially targeted by
the ASP at both facilities. CONCLUSIONS: To be effective, ASPs need an enormous
amount of "timely" information. Members of the ASP at IH report these new
applications help them improve antibiotic use by allowing efficient, timely
review and effective prioritization of patients receiving antimicrobials in order
to optimize patient care.
PMID- 25848420
TI - Implementation of an audio computer-assisted self-interview (ACASI) system in a
general medicine clinic: patient response burden.
AB - BACKGROUND: Routine implementation of instruments to capture patient-reported
outcomes could guide clinical practice and facilitate health services research.
Audio interviews facilitate self-interviews across literacy levels. OBJECTIVES:
To evaluate time burden for patients, and factors associated with response times
for an audio computer-assisted self interview (ACASI) system integrated into the
clinical workflow. METHODS: We developed an ACASI system, integrated with a
research data warehouse. Instruments for symptom burden, self-reported health,
depression screening, tobacco use, and patient satisfaction were administered
through touch-screen monitors in the general medicine clinic at the Cook County
Health & Hospitals System during April 8, 2011-July 27, 2012. We performed a
cross-sectional study to evaluate the mean time burden per item and for each
module of instruments; we evaluated factors associated with longer response
latency. RESULTS: Among 1,670 interviews, the mean per-question response time was
18.4 [SD, 6.1] seconds. By multivariable analysis, age was most strongly
associated with prolonged response time and increased per decade compared to < 50
years as follows (additional seconds per question; 95% CI): 50-59 years (1.4; 0.7
to 2.1 seconds); 60-69 (3.4; 2.6 to 4.1); 70-79 (5.1; 4.0 to 6.1); and 80-89
(5.5; 4.1 to 7.0). Response times also were longer for Spanish language (3.9; 2.9
to 4.9); no home computer use (3.3; 2.8 to 3.9); and, low mental self-reported
health (0.6; 0.0 to 1.1). However, most interviews were completed within 10
minutes. CONCLUSIONS: An ACASI software system can be included in a patient visit
and adds minimal time burden. The burden was greatest for older patients,
interviews in Spanish, and for those with less computer exposure. A patient's
self-reported health had minimal impact on response times.
PMID- 25848422
TI - Hospital closure and insights into patient dispersion: the closure of Saint
Vincent's Catholic Medical Center in New York City.
AB - BACKGROUND: Hospital closures are becoming increasingly common in the United
States. Patients who received care at the closing hospitals must travel to
different, often farther hospitals for care, and nearby remaining hospitals may
have difficulty coping with a sudden influx of patients. OBJECTIVES: Our
objectives are to analyze the dispersion patterns of patients from a closing
hospital and to correlate that with distance from the closing hospital for three
specific visit types: emergency, inpatient, and ambulatory. METHODS: In this
study, we used data from a health information exchange to track patients from
Saint Vincent's Medical Center, a hospital in New York City that closed in 2010,
to determine where they received emergency, inpatient, and ambulatory care
following the closure. RESULTS: We found that patients went to the next nearest
hospital for their emergency and inpatient care, but ambulatory encounters did
not correlate with distance. DISCUSSION: It is likely that patients followed
their ambulatory providers as they transitioned to another hospital system.
Additional work should be done to determine predictors of impact on nearby
hospitals when another hospital in the community closes in order to better
prepare for patient dispersion.
PMID- 25848421
TI - Convergent evolution of health information management and health informatics: a
perspective on the future of information professionals in health care.
AB - Clearly defined boundaries are disappearing among the activities, sources, and
uses of health care data and information managed by health information management
(HIM) and health informatics (HI) professionals. Definitions of the professional
domains and scopes of practice for HIM and HI are converging with the
proliferation of information and communication technologies in health care
settings. Convergence is changing both the roles that HIM and HI professionals
serve in their organizations as well as the competencies necessary for training
future professionals. Many of these changes suggest a blurring of roles and
responsibilities with increasingly overlapping curricula, job descriptions, and
research agendas. Blurred lines in a highly competitive market create confusion
for students and employers. In this essay, we provide some perspective on the
changing landscape and suggest a course for the future. First we review the
evolving definitions of HIM and HI. We next compare the current domains and
competencies, review the characteristics as well as the education and
credentialing of both disciplines, and examine areas of convergence. Given the
current state, we suggest a path forward to strengthen the contributions HIM and
HI professionals and educators make to the evolving health care environment.
PMID- 25848424
TI - Erratum to: identifying consumer's needs of health information technology through
an innovative participatory design approach among English- and Spanish-speaking
urban older adults.
PMID- 25848423
TI - Collaboration leads to enhanced curriculum.
AB - BACKGROUND: In 2007, we initiated a health information management (HIM) track of
our biomedical informatics graduate program, and subsequent ongoing program
assessment revealed a confluence of topics and courses within HIM and clinical
informatics (CI) tracks. We completed a thorough comparative analysis of
competencies derived from AMIA, AHIMA, and CAHIIM. Coupled with the need to
streamline course offerings, the process, described in this paper allowed new
opportunities for faculty collaboration, resulted in the creation of a model
assessment for best practice in courses, and led to new avenues of growth within
the program. OBJECTIVE: The objective of the case study is to provide others in
the informatics educational community with a model for analysis of curriculum in
order to improve quality of student learning. METHODS: We describe a case study
where an academic informatics program realigned its course offerings to better
reflect the HIM of today, and prepare for challenges of the future. Visionary
leadership, intra-departmental self-analysis and alignment of the curriculum
through defined mapping process reduced overlap within the CI and HIM tracks.
Teaching within courses was optimized through the work of core faculty
collaboration. RESULTS: The analysis of curriculum resulted in reduction of
overlap within course curriculum. This allowed for additional and new course
content to be added to existing courses. CONCLUSIONS: Leadership fostered an
environment where top-down as well as bottom-up collaborative assessment
activities resulted in a model to consolidate learning and reduce unnecessary
duplication within courses. A focus on curriculum integration, emphasis on course
alignment and strategic consolidation of course content raised the quality of
informatics education provided to students. Faculty synergy was an essential
component of this redesign process. Continuous quality improvement strategy
included an ongoing alignment of curriculum and competencies through a
comparative analysis approach. Through these efforts, new innovation was
possible.
PMID- 25848425
TI - Cerebral lesions in patients undergoing coronary artery bypass grafting in
relation to asymptomatic carotid and vertebral artery stenosis.
AB - OBJECTIVES: Carotid artery stenosis (CAS) and vertebral artery stenosis (VAS) are
associated with cerebral infarction after coronary artery bypass graft surgery
(CABG). It remains unclear whether this association is causal. We investigated
the associations between neurologically asymptomatic CAS and VAS and the
occurrence of subclinical cerebral lesions after CABG verified by magnetic
resonance imaging. METHODS: CABG patients were included and CAS and VAS were
identified by magnetic resonance angiography. Cerebral magnetic resonance imaging
was performed to identify new post-operative subclinical cerebral lesions. The
associations between CAS/VAS post-operative cerebral lesions were investigated.
RESULTS: Forty-six patients were included in the study. 13% had significant CAS
and 11% had significant VAS. Thirty-five percent had new cerebral infarction
postoperatively. We found a significant association between the presence of
cerebral vessel stenosis and acute cerebral infarction (67% vs. 27%, p = 0.047).
However none of the patients with stenosis had isolated cerebral lesions in the
ipsilateral vascular territory. CONCLUSION: Asymptomatic CAS and VAS is common in
CABG patients and is associated with an increased risk of postoperative cerebral
infarction. Our study suggests that asymptomatic CAS and VAS primarily are risk
markers rather than causal factors for cerebral infarction after CABG.
PMID- 25848426
TI - Long-term results of combined aortoiliac and infrainguinal arterial
reconstruction for the treatment of critical limb ischemia.
AB - OBJECTIVE: This study was designed to investigate our long-term experience with
combined iliac endovascular therapy (EVT) and infrainguinal bypass to treat
critical limb ischemia (CLI) and compare outcomes to those of patients who
underwent surgery for aortoiliac lesions. MATERIALS AND METHODS: From April 2000
to June 2013, 57 patients (58 limbs) underwent an infrainguinal bypass combined
with aortoiliac reconstruction to treat CLI. Eighteen limbs were treated by
bypass alone and 8 limbs were treated by bypass with EVT for aortoiliac lesions
(Bypass group). Thirty-two limbs were subjected to EVT alone for iliac lesions
(EVT group). RESULTS: Preoperative limb ischemia was more severe in the EVT
group. There were no significant differences in major procedure-related
complications (chi(2) test, P = 0.853), systemic complications (P = 0.853), and
mortality (P = 0.916) between the 2 groups. The limb salvage rates were 92% at 1,
3, and 5 years in the Bypass group and 93% at 1, 3, and 5 years in the EVT group,
with no significant difference observed between the groups (Kaplan-Meier, log
rank test, P = 0.616). CONCLUSION: Infrainguinal surgical reconstruction combined
with an iliac EVT is an acceptable strategy for managing patients with CLI.
PMID- 25848428
TI - Aortic fenestration for type B chronic aortic dissection complicated with lower
limb malperfusion induced by walking exercise.
AB - We report a case of a 55-year-old male with type B-chronic aortic dissection.
Patient presented with intermittent claudication due to limb malperfusion
resulting from expansion of a patent false lumen during walking regardless of
normal range ankle-brachial index (ABI) at rest. Preoperative stress vascular
ultrasonography was an effective modality for proper diagnosis. We should be
concerned of reversible ischemia due to the dissection flap in patients with type
B aortic dissection. Fenestration of the aorta can be a choice of treatment in
such patients. The patient has been doing well with no ischemia for 3.5 years
after the operation.
PMID- 25848427
TI - Endovascular Treatment of Iliac Vein Compression (May-Thurner) Syndrome:
Angioplasty and Stenting with or without Manual Aspiration Thrombectomy and
Catheter-Directed Thrombolysis.
AB - PURPOSE: May-Thurner syndrome (MTS) is a rare clinical entity featuring venous
obstruction of the left lower extremity. The aim of the present study was to
report our experience with MTS and to evaluate the utility of treatment using
endovascular techniques. MATERIALS AND METHODS: We retrospectively analyzed data
on 23 MTS patients (21 females, two males; mean age 44 +/- 15 years). Eighteen
patients presented with deep vein thrombosis (DVT) and five with symptoms
associated with chronic venous hypertension (CVH). DVT patients were treated via
thromboaspiration, catheter-directed thrombolysis, and angioplasty; followed by
stent placement. CVH patients were treated with angioplasty and stent placement
alone. All patients were followed-up using Doppler ultrasonography and computed
tomography venography. RESULTS: Complete left common iliac vein patency was
achieved in 21 of the 23 patients (technical success rate: 91,3%). Complete
thrombolysis was attained by 14 of the 18 DVT patients (77.7%). The mean clinical
and radiological follow-up time was 15.2 +/- 16.1 months. Upon follow-up,
complete symptomatic regression was observed in 19 of the 23 patients (82.6%).
Stent patency was complete in 19 of the 21 patients (90.4%) who received stents.
Restenosis occurred in two patients. No treatment-related mortality or morbidity
was observed. CONCLUSION: Endovascular treatment of MTS is safe and effective and
reduces symptoms in most patients, associated with high medium-term patency
rates.
PMID- 25848429
TI - Abdominal aortic aneurysm complicated by intestinal malrotation.
AB - Intestinal malrotation (IM) is an anomaly of fetal intestinal rotation that
usually presents in the first month of life; it is rare for malrotaion to present
in adulthood. Furthermore, the presentation of IM in conjunction with Abdominal
aortic aneurysm is extremely rare and may require consideration with respect to
the surgical approach and exposure of the abdominal aorta. We herein report a
case of an abdominal aortic aneurysm complicated by intestinal malrotation.
PMID- 25848430
TI - Acute Pulmonary Thromboembolism and Deep Vein Thrombosis during the Medical
Treatment of Acute Aortic Dissection was Successfully Treated by the Combination
of Inferior Vena Cava Filter Installation and Anti-Coagulant Therapy: A Case
Report.
AB - A 71-year-old woman was admitted with Stanford type A acute aortic dissection
(AAD). Computed tomography (CT) revealed thrombosis of the false lumen, and we
planned to treat medically. She developed transient pleural effusion and
hypoxemia, which persisted despite her pleural effusion disappeared. We performed
CT and found a large thrombus in the pulmonary artery and femoral vein. We
administered low dose- unfractionated heparin and installed a retrievable
inferior vena cava filter, which caused the thrombus in the pulmonary artery to
disappeared without exacerbating AAD. Our strategy seems to be suitable for acute
pulmonary thromboembolism that occurs during the treatment of AAD.
PMID- 25848431
TI - Ruptured pancreaticoduodenal artery aneurysm associated with median arcuate
ligament compression and aortic dissection successfully treated with
embolotherapy.
AB - A 51-year-old man with a ruptured pancreaticoduodenal artery (PDA) aneurysm
caused by compression of the celiac artery by the median arcuate ligament and
aortic dissection involving the celiac axis was transferred to our hospital for
endovascular treatment. A 4-F catheter was advanced into the superior mesenteric
artery through the narrow true lumen via the left brachial artery, and coil
embolization of the aneurysm was successfully performed. In this case, rapid
increase of blood flow in the superior mesenteric artery, which compensated for
the decreased celiac blood flow by aortic dissection, increased hemodynamic
stress on the PDA, leading to aneurysmal rupture.
PMID- 25848432
TI - Two dehiscences of the aortic valve commissure and cusp with progressive acute
aortic regurgitation.
AB - A 54-year-old female with acute heart failure due to aortic regurgitation (AR)
was admitted to our hospital. Following admission, her condition worsened
progressively; thus, surgery was performed prematurely. During surgery, two
dehiscences were visualized in the aortic valve commissure between the right and
left cusps and the upper part of the left coronary artery ostium. However we
scheduled aortic valve replacement (AVR) at first, we made the shift to perform
the aortic root replacement for reinforcement of the aortic wall around the left
coronary artery ostium. We describe a rare case of two dehiscences at the aortic
root, which is the first report.
PMID- 25848433
TI - Internal iliac artery aneurysmo-colonic fistula after endovascular stent-graft
repair: a case report.
AB - We describe rare ilio-enteric fistula that developed after endovascular repair of
a left internal iliac artery aneurysm (IIAA). An 83-year-old man with a history
of previous surgeries via laparotomies suddenly developed a high fever 3 years
after undergoing endovascular abdominal aortic repair (EVAR) with a stent-graft
to treat a left isolated IIAA. Computed tomography imaging revealed a fistula
between the IIAA and the sigmoid colon. A colostomy was created because severe
intraperitoneal adhesions prevented resection of the IIAA. The postoperative
course was uneventful and the patient remained free of infection without
antibiotics. Residual aneurysms can cause complications after EVAR.
PMID- 25848434
TI - Ascending aortic false aneurysm formation associated with rupture of acute type a
aortic dissection.
AB - A 63-year-old man with ruptured acute type A aortic dissection was referred to
our hospital. Computed tomography showed a false aneurysm arising from the false
lumen located beside the ascending aorta. His hemodynamic status was stable
inspite of the ruptured acute aortic dissection. We consider that the containment
of the false aneurysm by thin mediastinal structures prevented worsening of his
hemodynamic status, and this is extremely rare.
PMID- 25848435
TI - Open surgical repair for a ruptured abdominal aortic aneurysm with a horseshoe
kidney.
AB - Horseshoe kidney is a congenital anomaly characterized by medial fusion of the
bilateral kidneys. Treatment for an abdominal aortic aneurysm (AAA) with a
horseshoe kidney is a technical challenge because of the complex anatomy. We
report a successful open surgical repair for a ruptured AAA with a horseshoe
kidney. An aortic grafting was performed with division of the renal isthmus
through a transperitoneal approach. In the case of a ruptured AAA, quick open
surgery is the most reliable treatment. If a horseshoe kidney coexists,
transperitoneal approach with division of the renal isthmus provides good
surgical field for an aortic grafting.
PMID- 25848436
TI - Surgical repair for popliteal venous aneurysm causing severe or recurrent
pulmonary thromboembolism: three case reports.
AB - Poplitealvenous aneurysms (PVA) are associated with deep venous thrombosis and
recurrentpulmonary thromboembolism (PE). We report three cases of PVA. In all
three patients the first sign of PVA was acute PE; in one case, the PE was
recurrent. Computed tomography and duplex ultrasonography revealed not only PE
but also popliteal venous dilatation with thrombus. Surgical reconstruction was
performed in each case after treatment for PE. No postoperative complications
occurred, including recurrent PE. Surgical repair of PVA is safe and is a
recommended treatment.
PMID- 25848437
TI - Hybrid endovascular repair for an arch aneurysm combined with aberrant right
subclavian artery.
AB - This report describes a hybrid endovascular approach to a 9.3-cm saccular
aneurysm of the left sided aortic arch combined with an aberrant right subclavian
artery. The two-step procedure consisted of a bilateral carotid-subclavian
bypass, followed by an ascending aorta-bicarotid bypass and completed by an
endovascular exclusion of the aneurysm by covering the whole aortic arch and its
branches. The patient had no postoperative complications and was discharged 10
postoperative day. Hybrid procedures may be useful in complex aortic arch
pathologies and may reduce postoperative complications in comparison with
conventional open surgery.
PMID- 25848438
TI - Emergent rescue operation for expanding mycotic pseudoaneurysm causing
hemoptysis, originating from right subclavian artery.
AB - Mycotic pseudoaneurysm of the subclavian artery is uncommon and its therapeutic
strategy has not been established. We report a case of 81-year-old woman with
mycotic pseudoaneurysm in the right subclavian artery. Blood culture showed
Enterobacter cloacae. Because of hemoptysis and acute expansion of the
pseudoaneurysm, emergent coil embolization was performed, but failed. The patient
underwent urgent operation for an en-bloc resection of the pseudoaneurysm after
aorto-right common carotid artery bypass followed by omentum packing. The patient
underwent continuous wound irrigation for 3 weeks. The postoperative course was
uneventful and without recurrence of infection.
PMID- 25848439
TI - Isolated Transverse Clivus Fracture without Neurodeficit: Case Report and Review
of Literature.
AB - BACKGROUND: Clivus is a bony surface in the posterior cranial fossa, serving as
the support of the brainstem and thus neighboring important structures because of
its location. Skull base fractures that cannot be shown by conventional
radiography can be clearly imaged by high-resolution bone window computed
tomography. CASE REPORT: A 44 years-old male referred to the emergency department
because of a traffic accident in the car. His only complaint was a severe
neckache. His X-ray examination showed no pathology. The computed tomographic
examination showed no parenchymal pathology, but a isolated transverse fracture
in the clivus. CONCLUSIONS: The computed tomographic examination showed isolated
transverse fracture in the clivus our case presented in this paper is the first
case of transverse clivus fracture without additional cranial bone fracture and
neurologic deficit in the literature.
PMID- 25848440
TI - Embolization of a True Giant Splenic Artery Aneurysm Using NBCA Glue - Case
Report and Literature Review.
AB - BACKGROUND: Although splenic artery aneurysms (SAAs) are common, their giant
forms (more than 10 cm in diameter) are rare. Because of the variety of forms and
locations of these aneurysms, there are a lot of therapeutic methods to choose.
In our case of a giant true aneurysm we performed an endovascular embolization
with N-butyl-cyano-acrylate (NBCA) glue. To our knowledge it is the first
reported case of this method of treatment of true giant SAA. CASE REPORT: A 74
year-old male patient with symptomatic giant SAA (13 cm) was urgently admitted to
our hospital for the diagnostic and therapeutic procedures. Due to the general
health condition, advanced age and the large size of the aneurysm we decided to
perform an endovascular treatment with N-butyl-cyano-acrylate (NBCA) glue.
CONCLUSIONS: The preaneurysmal part of splenic artery was occluded completely
with exclusion of the aneurysm. No splenectomy was needed. The patient was
discharged in good general condition Embolization with NBCA can be an efficient
method to treat the giant SAA.
PMID- 25848441
TI - Internal carotid artery blister-like aneurysm caused by Aspergillus - case
report.
AB - BACKGROUND: Blister-like aneurysm of the supraclinoid internal carotid artery
(ICA) is a well-documented cause of subarachnoid hemorrhage. Generally, this type
of aneurysm is associated with various conditions such as hypertension,
arteriosclerosis, and ICA dissection. Although Aspergillus is the most common
organism causing intracranial fungal aneurysmal formation, there is no report of
a blister-like aneurysm caused by Aspergillus infection. CASE REPORT: An 83-year
old man received corticosteroid pulse therapy followed by oral steroid therapy
for an inflammatory pseudotumor of the clivus. Two months later, the patient was
transported to an emergency department due to the diffuse subarachnoid
hemorrhage, classified as Fisher group 4. Subsequent 3D computed tomography
angiogram revealed a blister-like aneurysm at the superior wall of the left ICA.
Six days later, the patient died of subarachnoid hemorrhage caused by the left
ICA aneurysm rerupture. Autopsy revealed proliferation of Aspergillus hyphae in
the wall of the aneurysm. Notably, that change was present more densely in the
inner membrane than in the outer one. Thus, it was considered that Aspergillus
hyphae caused infectious aneurysm formation in the left ICA via hematogenous
seeding rather than direct invasion. CONCLUSIONS: The blister-like aneurysm is a
rare but important cause of subarachnoid hemorrhage. This case report documents
another cause of blister-like aneurysms, that is an infectious aneurysm
associated with Aspergillus infection.
PMID- 25848442
TI - Composite grafting of a distal thumb amputation: a case report and review of
literature.
AB - OBJECTIVE: We report a case in which an avulsion-amputation of the thumb proximal
to the lunula was repaired by reattaching the amputated segment as a composite
graft. The graft demonstrated complete survival with only a minimal sacrifice in
length. METHODS: A 23-year-old man presented 4 hours after an avulsion injury of
the thumb with associated distal and proximal phalanx fractures. The amputated
segment included the sterile and germinal matrix. He underwent defatting and
composite grafting of the amputated segment followed by K-wire fixation of his
proximal phalanx fracture. RESULTS: In his 1-week follow-up, the patient's
composite graft-including his nail bed-demonstrated complete survival. At one
month, the composite graft maintained stable soft tissue coverage and showed
signs of nail plate regrowth. Four months after repair, he was able to return to
light duty and was advanced to full duty within 5 months. He continued to report
gradually improving hypersensitivity at the margins of the graft and stiffness of
the interphalangeal joint. At five months he regained full mobility of his
carpometacarpal joint. The range of motion of his interphalangeal and
metacarpophalangeal joint were 0 to 10 degrees and 0 to 25 degrees, respectively.
He was able to oppose his thumb to all 4 digits. Six months after repair, he
demonstrated protective sensation of the tip of the thumb. CONCLUSION: Composite
grafting of the thumb, even in less than ideal cases, can still provide useful
length for function as a opposable post and can be considered in reconstruction
of thumb amputations at or proximal to the lunula.
PMID- 25848443
TI - Fibrous dysplasia: an overview of disease process, indications for surgical
management, and a case report.
AB - INTRODUCTION: First described by Von Recklinghausen in 1891, fibrous dysplasia is
a developmental defect of osseous tissue such that bone is produced with an
abnormally thin cortex and marrow is replaced with fibrous tissue that
demonstrates characteristic ground-glass appearance on x-ray examination. The
underlying defect in fibrous dysplasia is a mutation of the GNAS1 gene, which
leads to constitutive activation of gene products that preclude the maturation of
osteoprogenitor cells and lead to development of abnormal bone matrix,
trabeculae, and collagen, produced by undifferentiated mesenchymal cells. There
exists a mainly self-limiting form of fibrous dysplasia classified as monostotic,
which is characterized by dysplastic bone in a single location that remains
relatively stable throughout life and a polyostotic form, which can exhibit
aggressive growth placing adjacent structures at risk for compressive sequelae.
METHODS: We present the surgical management of an unusual case of monostotic
fibrous dysplasia, which exhibited aggressive growth with mass effect, and late
presentation, both uncharacteristic features for the monostotic form. The authors
also performed a comprehensive review of the literature and discuss the disease
process, management options, and indications for surgical treatment. RESULTS: An
overview of the disease process and management options is presented. The authors
also present details of reconstruction in an unusual form of symptomatic
monostotic fibrous dysplasia. CONCLUSION: Conservative management is usually the
mainstay of therapy in asymptomatic cases of fibrous dysplasia. In patients
fulfilling criteria for surgical management, craniofacial reconstruction offers a
viable option in the surgeon's armamentarium, providing good functional and
cosmetic outcomes.
PMID- 25848444
TI - Lymphatic mapping in the treatment of chronic seroma: a case series.
AB - OBJECTIVE: Seromas or lymphoceles are common postoperative complications. This
series presents 3 patients with lower extremity seromas refractory to treatment
that required lymphatic mapping and lymphatic ligation for closure, and in 1
case, diagnosis. METHODS: Lymphatic mapping procedure consisted of intraoperative
injection of subcutaneous tissue with methylene blue distal to the seroma with
observation of dye effluence from transected or injured lymphatics draining into
area of seroma. RESULTS: In 2 patients, methylene blue dye absorption into
lymphatic vessels allowed for optimized visual identification of lymphatic leak
and contrast against surrounding tissues. In the third patient, where no
lymphocele leak was found, the study was diagnostic and helped to find an
alternate etiology for the recurrent seroma. CONCLUSION: Lymphatic mapping with
methylene blue dye is an effective tool in the evaluation and diagnosis of
chronic seroma.
PMID- 25848445
TI - Longitudinal slit procedure in addition to negative pressure wound therapy for a
refractory wound with exposed achilles tendon.
AB - OBJECTIVE: This case report reviews features of negative pressure wound therapy,
particularly for the exposed Achilles tendon, and describes an additional
effective procedure. METHODS: An 87-year-old man presented with a soft-tissue
defect measuring 3*5 cm with the exposed Achilles tendon as a sequela of deep
burn. The condition of his affected leg was ischemic because of arteriosclerosis.
We used negative pressure wound therapy and made 2 longitudinal slits penetrating
the tendon to induce blood flow from the ventral side to the dorsal surface.
RESULTS: By this combination therapy, the surface of the exposed Achilles tendon
was completely epithelialized and the tendon was spared without disuse syndrome.
CONCLUSIONS: The authors conclude that this combination therapy is useful for
covering the widely exposed tendon in aged patients.
PMID- 25848446
TI - Cement burn.
PMID- 25848447
TI - [Renal, pancreatic and adrenal masses].
PMID- 25848448
TI - [Histopathological study of cervical lymphadenopathy in Yaounde, Cameroon].
PMID- 25848449
TI - [One case of vitreous asteroid degeneration].
PMID- 25848450
TI - [Salivary gland tumors, clinico-epidemiological study and radioanatomy
correlation: retrospective study of 148 cases].
PMID- 25848451
TI - Mammary-like adenocarcinoma of the vulva associated to Paget's disease: a case
report.
AB - Mammary-like adenocarcinoma of the vulva associated to Paget's disease is
exceedingly rare. So, it is very important to perform all the pathological and
immunohistochemical investigations to achieve differential diagnosis from both a
metastatic lesion from an orthotopic breast cancer and a vulvar adnexal tumor.
This report describes a case of vulvar Paget's disease associated with underlying
mammary-like adenocarcinoma diagnosed in the Department of Obstetrics and
Gynecology of Farhat Hached university hospital of Sousse in Tunisia. We also
review previously reported cases of primary breast-like carcinoma of the vulva
with or without Paget's disease.
PMID- 25848452
TI - [Scarf osteotomy in the treatment of hallux valgus: about 19 cases].
PMID- 25848453
TI - [Influence of caretakers' behavior on the quality of life of patients admitted
for upper gastrointestinal bleeding in Lome campus University Hospital (Togo)].
PMID- 25848454
TI - [Chilaiditi syndrome in a newborn, in a case report].
PMID- 25848455
TI - Ambulatory blood pressure measurement in the main cities of Cameroon: prevalence
of masked and white coat hypertension, and influence of body mass index.
AB - INTRODUCTION: Identifying White Coat Hypertension (WCH) may avoid inappropriate
commitment of individuals to lifelong and costly blood pressure (BP) lowering
medications'. We assessed the prevalence and determinants of WCH in urban
clinical settings in Cameroon. METHODS: Participants were a consecutive sample of
adults, who underwent ambulatory BP measurements (ABPM) for the diagnosis of
hypertension and evaluation of treatmentin three referral cardiac clinics in the
cities of Yaounde and Douala, between January 2006 and July 2011. WCH was defined
as an office-based systolic (or diastolic) BP >= 140(90) mmHg together with an
average day time ambulatory systolic (and diastolic) BP < 135(85) mmHg. RESULTS:
Of the 500 participants included, 188 (37.6%) were women, 230 (46%) were
nonsmokers and 53 (10.6%) had diabetes mellitus. The mean age was 51.6+/-10.2
years. The ABPM readings were higher in men than in women (p<0.05).The prevalence
of WCH was 26.4% overall, 39.3% in women and 22.4% in men (p=0.01).In
multivariable analysis, body mass index was the only significant determinant of
WCH (Odds ratio= 1.15(95% confidence intervals: 1.00-1.43), p<0.05). CONCLUSION:
The prevalence of WCH was high in our study population and was correlated only
with BMI. Accurate measurement of BP and appropriate diagnosis of hypertension
using ABPM in this setting may help limiting the consequences of over estimating
hypertension severity on individuals, families and health systems.
PMID- 25848456
TI - Plasma oxidized low density lipoprotein cholesterol correlates inversely with
testosterone in young adult male smokers.
AB - INTRODUCTION: There are indications that oxidized low density lipoprotein
cholesterol (Ox-LDLC) may play an important role in cardiovascular disease (CVD)
events. In most developing countries, the interplay between the different lipid
fractions and cigarette smoking has not been studied. This study assessed the
effect of cigarette smoking on the alterations in plasma lipid fractions and
their associations with the gonadal hormone, testosterone (T). METHODS: One
hundred and sixty male participants, consisting of eighty smokers and eighty
apparently healthy non-smokers were recruited. Anthropometric indices and
biochemical parameters were determined using standard procedures. RESULTS:
Significant increases were obtained in plasma total cholesterol (TC),
triglyceride (TG), oxidized low density lipoprotein (Ox-LDLC) and Ox-LDLC/TT
ratio (p<0.001) in smokers compared with the non-smokers. Plasma high density
cholesterol (HDLC) (p<0.001) was significantly reduced in smokers compared with
the non-smokers. The plasma mean T result was not significantly different from
the non-smokers, but inversely correlated with Ox-LDLC and significantly
correlated with the lipids and lipoproteins. Significantly high plasma TC, TG and
LDLC (p<0.001) and low HDLC (p<0.001) were also obtained in smokers when co
founding factors such as duration and number of cigarette smoked per day were
applied. CONCLUSION: This study showed an inverse correlation between Ox-LDLC and
testosterone as well as strong association between the number of tobacco and
cigarettes usage per day. These changes in part, could be major causes of
premature CVD and decreased fertility in young adults.
PMID- 25848457
TI - [Traumatic compression syndrome: report of a case].
PMID- 25848458
TI - Environmental surveillance of poliovirus and non-polio enterovirus in urban
sewage in Dakar, Senegal (2007-2013).
AB - INTRODUCTION: Global poliomyelitis eradication initiative relies on (i)
laboratory based surveillance of acute flaccid surveillance (AFP) to monitor the
circulation of wild poliovirus in a population, and (ii) vaccination to prevent
its diffusion. However, as poliovirus can survive in the environment namely in
sewage, environmental surveillance (ES) is of growing importance as the
eradication target is close. This study aimed to assess polioviruses and non
polio enteroviruses circulation in sewage drains covering a significant
population of Dakar. METHODS: From April 2007 to May 2013, 271 specimens of raw
sewage were collected using the grab method in 6 neighborhoods of Dakar. Samples
were processed to extract and concentrate viruses using polyethylene glycol and
Dextran (two-phase separation method). Isolation of enteroviruses was attempted
in RD, L20B and Hep2 cell lines. Polioviruses were identified by RT-PCR and
Elisa. Non Polio Enteroviruses (NPEVs) were identified by RT-PCR and
microneutralisation tests. RESULTS: Polioviruses and NPEVs were respectively
detected in 34,3% and 42,8% sewage samples. No wild poliovirus neither
circulating vaccine-derived Poliovirus (cVDPV) was detected. Neutralization
assays have identified 49 non polio enteroviruses that were subsequently
classified in 13 serotypes belonging to HEV-A (22, 4%), HEV-B (12, 24%), HEV-C
(26, 53%) and HEV-D (6, 12%) species. CONCLUSION: This study is the first
documentation of enteroviruses environmental detection in Senegal. It shows the
usefulness of environmental surveillance for indirect monitoring of the
circulation and distribution of enteroviruses in the community.
PMID- 25848459
TI - Genotypes and viral variants in chronic hepatitis B: A review of epidemiology and
clinical relevance.
AB - The Hepatitis B Virus (HBV) has a worldwide distribution and is endemic in many
populations. It is constantly evolving and 10 genotypic strains have been
identified with varying prevalences in different geographic regions. Numerous
stable mutations in the core gene and in the surface gene of the HBV have also
been identified in untreated HBV populations. The genotypes and viral variants
have been associated with certain clinical features of HBV related liver disease
and Hepatocellular carcinoma. For example Genotype C is associated with later
hepatitis B e antigen (HBeAg) seroconversion, and more advanced liver disease.
Genotype A is associated with a greater risk of progression to chronicity in
adult acquired HBV infections. Genotype D is particularly associated with the
precore mutation and HBeAg negative chronic hepatitis B (CHB). The genotypes
prevalent in parts of West Africa, Central and South America, E, F and H
respectively, are less well studied. Viral variants especially the Basal Core
Promotor mutation is associated with increased risk of fibrosis and cancer of the
liver. Although not currently part of routine clinical care, evaluation of
genotype and viral variants may provide useful adjunctive information in
predicting risk about liver related morbidity in patients with CHB.
PMID- 25848460
TI - Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a
cirrhotic liver.
AB - Spontaneous bacterial peritonitis (SBP) is a frequent, life-threatening bacterial
infection in patients with liver cirrhosis and ascites. Portal hypertension leads
to increased bacterial translocation from the intestine. Failure to eliminate
invading pathogens due to immune defects associated with advanced liver disease
on the background of genetic predisposition may result in SBP. The efficacy of
antibiotic treatment and prophylaxis has declined due to the spread of multi
resistant bacteria. Patients with nosocomial SBP and with prior antibiotic
treatment are at a particularly high risk for infection with resistant bacteria.
Therefore, it is important to adapt empirical treatment to these risk factors and
to the local resistance profile. Rifaximin, an oral, non-absorbable antibiotic,
has been proposed to prevent SBP, but may be useful only in a subset of patients.
Since novel antibiotic classes are lacking, we have to develop prophylactic
strategies which do not induce bacterial resistance. Farnesoid X receptor
agonists may be a candidate, but so far, clinical studies are not available. New
diagnostic tests which can be carried out quickly at the patient's site and
provide additional prognostic information would be helpful. Furthermore, we need
tools to predict antibiotic resistance in order to tailor first-line antibiotic
treatment of spontaneous bacterial peritonitis to the individual patient and to
reduce mortality.
PMID- 25848461
TI - Non-alcoholic fatty liver disease and psoriasis: So far, so near.
AB - Psoriasis is a chronic inflammatory immune-mediated skin diseases which is
frequently associated to comorbidities. Non-alcoholic fatty liver disease (NAFLD)
is defined as an excessive accumulation of triglycerides in hepatocytes and
includes a wide spectrum of liver conditions ranging from relatively benign
steatosis to non-alcoholic steatohepatitis with fatty infiltration and lobular
inflammation and to cirrhosis and end-stage liver disease. Actually, psoriasis is
considered a systemic diseases associated to comorbidities, as metabolic syndrome
and NAFLD is seen the hepatic manifestation of the metabolic syndrome. The
possible link between psoriasis, obesity and metabolic syndrome, which are known
risk factors for NAFLD has been recently documented focusing in the crucial role
of the adipose tissue in the development of the inflammatory background sharing
by the above entities. According to recent data, patients with psoriasis show a
greater prevalence of NAFLD and metabolic syndrome than the general population.
Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver
fibrosis than those with NAFLD and without psoriasis. The link between these
pathological conditions appears to be a chronic low-grade inflammatory status.
The aim of this review is to focus on the multiple aspects linking NAFLD and
psoriasis, only apparently far diseases.
PMID- 25848462
TI - Hepatitis C virus syndrome: A constellation of organ- and non-organ specific
autoimmune disorders, B-cell non-Hodgkin's lymphoma, and cancer.
AB - The clinical course of chronic hepatitis C virus (HCV) infection is characterized
by possible development of both liver and extrahepatic disorders. The tropism of
HCV for the lymphoid tissue is responsible for several immune-mediated disorders;
a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion
of patients with HCV infection, are responsible for the production of different
autoantibodies and immune-complexes, such as mixed cryoglobulins. These
serological alterations may characterize a variety of autoimmune or neoplastic
diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of
circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated
and lymphoproliferative disorders; interestingly, in some cases the disease may
evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential
as suggested by several clinico-epidemiological and laboratory studies; in
addition to hepatocellular carcinoma that represents the most frequent HCV
related malignancy, a causative role of HCV has been largely demonstrated in a
significant percentage of patients with isolated B-cells non-Hodgkin's lymphomas.
The same virus may be also involved in the pathogenesis of papillary thyroid
cancer, a rare neoplastic condition that may complicate HCV-related thyroid
involvement. Patients with HCV infection are frequently asymptomatic or may
develop only hepatic alteration, while a limited but clinically relevant number
can develop one or more autoimmune and/or neoplastic disorders. Given the large
variability of their prevalence among patients' populations from different
countries, it is possible to hypothesize a potential role of other co-factors,
i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra
hepatic diseases.
PMID- 25848463
TI - Risk of hepatitis B virus reactivation in rheumatoid arthritis patients
undergoing biologic treatment: Extending perspective from old to newer drugs.
AB - Hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients
undergoing biological therapy is not infrequent. This condition can occur in
patients with chronic hepatitis B as well as in patients with resolved HBV
infection. Current recommendations are mainly focused on prevention and
management strategies of viral reactivation under tumor necrosis factor-alpha
inhibitors or chimeric monoclonal antibody rituximab. In recent years, growing
data concerning HBV reactivation in RA patients treated with newer biological
drugs like tocilizumab and abatacept have cumulated. In this review,
epidemiology, pathogenesis and natural history of HBV infection have been revised
first, mainly focusing on the role that specific therapeutic targets of current
biotechnological drugs play in HBV pathobiology; finally we have summarized
current evidences from scientific literature, including either observational
studies and case reports as well, concerning HBV reactivation under different
classes of biological drugs in RA patients. Taking all these evidences into
account, some practical guidelines for screening, vaccination, prophylaxis and
treatment of HBV reactivation have been proposed.
PMID- 25848464
TI - Diagnosis and treatment of hepatocellular carcinoma: An update.
AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to
high mortality rates in the general population; in cirrhotic patients, it is the
primary cause of death. The diagnosis is usually delayed in spite of at-risk
population screening recommendations, i.e., patients infected with hepatitis B or
C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular
abnormalities that lead to tumor angiogenesis and foster their dissemination
potential. The diagnosis is mainly based on imaging studies such as computed
tomography and magnetic resonance, in which lesions present a characteristic
classical pattern of early arterial enhancement followed by contrast medium
"washout" in late venous phase. On occasion, when imaging studies are not
conclusive, biopsy of the lesion must be performed to establish the diagnosis.
The Barcelona Clinic Liver Cancer staging method is the most frequently used
worldwide and recommended by the international guidelines of HCC management.
Currently available treatments include tumor resection, liver transplant,
sorafenib and loco-regional therapies (alcoholization, radiofrequency ablation,
chemoembolization). The prognosis of hepatocarcinoma is determined according to
the lesion's stage and in cirrhotic patients, on residual liver function.
Curative treatments, such as liver transplant, are sought in patients diagnosed
in early stages; patients in more advanced stages, were not greatly benefitted by
chemotherapy in terms of survival until the advent of target molecules such as
sorafenib.
PMID- 25848465
TI - Angiogenesis and liver fibrosis.
AB - Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes
place in chronic liver diseases (CLDs) that are characterized by inflammation and
progressive fibrosis. Because anti-angiogenic therapy has been found to be
efficient in the prevention of fibrosis in experimental models of CLDs, it is
suggested that blocking angiogenesis could be a promising therapeutic option in
patients with advanced fibrosis. Consequently, efforts are being directed to
revealing the mechanisms involved in angiogenesis during the progression of liver
fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis
are closely related in both clinical and experimental conditions. Hypoxia is a
major inducer of angiogenesis together with inflammation and hepatic stellate
cells. These profibrogenic cells stand at the intersection between inflammation,
angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This
review mainly focuses to give a clear view on the relevant features that
communicate angiogenesis with progression of fibrosis in CLDs towards the-end
point of cirrhosis that may be translated into future therapies. The pathogenesis
of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non
alcoholic fatty liver disease and alcoholic liver disease are also discussed to
emphasize the various mechanisms involved in angiogenesis during liver
fibrogenesis.
PMID- 25848466
TI - Cirrhosis in children and adolescents: An overview.
AB - Several conditions, especially chronic liver diseases, can lead to cirrhosis in
children and adolescents. Most cases in clinical practice are caused by similar
etiologies. In infants, cirrhosis is most often caused by biliary atresia and
genetic-metabolic diseases, while in older children, it tends to result from
autoimmune hepatitis, Wilson's disease, alpha-1-antitrypsin deficiency and
primary sclerosing cholangitis. The symptoms of cirrhosis in children and
adolescents are similar to those of adults. However, in pediatric patients, the
first sign of cirrhosis is often poor weight gain. The complications of pediatric
cirrhosis are similar to those observed in adult patients, and include
gastrointestinal bleeding caused by gastroesophageal varices, ascites and
spontaneous bacterial peritonitis. In pediatric patients, special attention
should be paid to the nutritional alterations caused by cirrhosis, since children
and adolescents have higher nutritional requirements for growth and development.
Children and adolescents with chronic cholestasis are at risk for several
nutritional deficiencies. Malnutrition can have severe consequences for both pre-
and post-liver transplant patients. The treatment of cirrhosis-induced portal
hypertension in children and adolescents is mostly based on methods developed for
adults. The present article will review the diagnostic and differential
diagnostic aspects of end-stage liver disease in children, as well as the major
treatment options for this condition.
PMID- 25848467
TI - Staging systems for hepatocellular carcinoma: Current status and future
perspectives.
AB - Hepatocellular carcinoma (HCC) is a major health concern worldwide and the third
cause of cancer-related death. Despite advances in treatment as well as careful
surveillance programs, the mortality rates in most countries are very high. In
contrast to other cancers, the prognosis and treatment of HCC depend on the tumor
burden in addition to patient's underlying liver disease and liver functional
reserve. Moreover, there is considerable geographic and institutional variation
in both risk factors attributable to the underlying liver diseases and the
management of HCC. Therefore, although many staging and/or scoring systems have
been proposed, there is currently no globally accepted system for HCC due to the
extreme heterogeneity of the disease. The aim of this review is to focus on
currently available staging systems as well as those newly reported in the
literatures since 2012. Moreover, we describe problems with currently available
staging systems and attempts to modify and/or add variables to existing staging
systems.
PMID- 25848468
TI - Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia.
AB - A "leaky gut" may be the cutting edge for the passage of toxins, antigens or
bacteria into the body, and may play a pathogenic role in advanced liver
cirrhosis and its complications. Plasma endotoxin levels have been admitted as a
surrogate marker of bacterial translocation and close relations of endotoxemia to
hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and
coagulation disturbances have been reported. Bacterial overgrowth, increased
intestinal permeability, failure to inactivate endotoxin, activated innate
immunity are all likely to play a role in the pathological states of bacterial
translocation. Therapeutic approach by management of the gut-liver axis by
antibiotics, probiotics, synbiotics, prebiotics and their combinations may
improve the clinical course of cirrhotic patients. Special concern should be paid
on anti-endotoxin treatment. Adequate management of the gut-liver axis may be
effective for prevention of liver cirrhosis itself by inhibiting the progression
of fibrosis.
PMID- 25848470
TI - Gender-based disparities in access to and outcomes of liver transplantation.
AB - Despite comprising 35% of transplants, the number of female transplant recipients
has continued to decline. Accordingly, there is a growing attention to the issue
of access to and outcomes of liver transplantation in women. The purpose of this
review is to critically evaluate the published literature on etiologies
contributing to gender-based disparities in liver transplantation focusing on the
steps from chronic liver disease through transplantation including disparities in
liver disease prevalence, access to liver transplant centers and transplant
waiting list, receipt of liver transplantation once listed and disparities in
post-liver transplantation outcomes. Our review finds factors contributing to
this disparity may include gender differences in the etiology of underlying liver
disease and patient and physician referral patterns, lifestyle and health care,
but also utilization of an imperfect organ allocation system based on the model
for end stage liver disease score and donor-recipient liver size matching. The
review also highlights the need for further research in the area of gender
disparity in order to develop appropriate approaches to address it and to improve
allocation of this precious resource in the future.
PMID- 25848469
TI - Endothelial dysfunction in cirrhosis: Role of inflammation and oxidative stress.
AB - This review describes the recent developments in the pathobiology of endothelial
dysfunction (ED) in the context of cirrhosis with portal hypertension and defines
novel strategies and potential targets for therapy. ED has prognostic
implications by predicting unfavourable early hepatic events and mortality in
patients with portal hypertension and advanced liver diseases. ED characterised
by an impaired bioactivity of nitric oxide (NO) within the hepatic circulation
and is mainly due to decreased bioavailability of NO and accelerated degradation
of NO with reactive oxygen species. Furthermore, elevated inflammatory markers
also inhibit NO synthesis and causes ED in cirrhotic liver. Therefore,
improvement of NO availability in the hepatic circulation can be beneficial for
the improvement of endothelial dysfunction and associated portal hypertension in
patients with cirrhosis. Furthermore, therapeutic agents that are identified in
increasing NO bioavailability through improvement of hepatic endothelial nitric
oxide synthase (eNOS) activity and reduction in hepatic asymmetric
dimethylarginine, an endogenous modulator of eNOS and a key mediator of elevated
intrahepatic vascular tone in cirrhosis would be interesting therapeutic
approaches in patients with endothelial dysfunction and portal hypertension in
advanced liver diseases.
PMID- 25848471
TI - Magnetic resonance imaging of the cirrhotic liver: An update.
AB - Noninvasive imaging has become the standard for hepatocellular carcinoma (HCC)
diagnosis in cirrhotic livers. In this review paper, we go over the basics of MR
imaging in cirrhotic livers and describe the imaging appearance of a spectrum of
hepatic nodules marking the progression from regenerative nodules to low- and
high-grade dysplastic nodules, and ultimately to HCCs. We detail and illustrate
the typical imaging appearances of different types of HCC including focal, multi
focal, massive, diffuse/infiltrative, and intra-hepatic metastases; with emphasis
on the diagnostic value of MR in imaging these lesions. We also shed some light
on liver imaging reporting and data system, and the role of different magnetic
resonance imaging (MRI) contrast agents and future MRI techniques including the
use of advanced MR pulse sequences and utilization of hepatocyte-specific MRI
contrast agents, and how they might contribute to improving the diagnostic
performance of MRI in early stage HCC diagnosis.
PMID- 25848472
TI - Hepatitis B in healthcare workers: Transmission events and guidance for
management.
AB - Hepatitis B virus (HBV) is the most efficiently transmissible of the bloodborne
viruses that are important in healthcare settings. Healthcare workers (HCWs) are
at risk for exposure to HBV from infected patients and, if infected, are
similarly at risk of transmitting HBV to patients. Published cases of HBV
transmission from HCW to patient are relatively rare, having decreased in
frequency following the introduction of standard (universal) precautions,
adoption of enhanced percutaneous injury precautions such as double-gloving in
surgery, and routine HBV vaccination of HCWs. Here we review published cases of
HCW-to-patient transmission of HBV, details of which have helped to guide the
creation of formal guidelines for the management of HBV-infected HCWs. We also
compare the published guidelines for the management of HBV-infected HCWs from
various governing bodies, focusing on their differences with regard to
vaccination requirements, viral load limits, frequency of monitoring, and
restrictions on practice. Importantly, while there are differences among the
recommendations from governing bodies, no guidelines uniformly restrict HBV
infected HCWs from performing invasive or exposure-prone procedures.
PMID- 25848473
TI - MiR-122 in hepatitis B virus and hepatitis C virus dual infection.
AB - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most
common causes of chronic liver diseases and hepatocelluar carcinomas. Over the
past few years, the liver-enriched microRNA-122 (miR-122) has been shown to
differentially regulate viral replication of HBV and HCV. It is notable that the
level of miR-122 is positively and negatively regulated by HCV and HBV,
respectively. Consistent with the well-documented phenomenon that miR-122
promotes HCV accumulation, inhibition of miR-122 has been shown as an effective
therapy for the treatment of HCV infection in both chimpanzees and humans. On the
other hand, miR-122 is also known to block HBV replication, and HBV has recently
been shown to inhibit miR-122 expression; such a reciprocal inhibition between
miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may
represent a potential therapy for treatment of HBV infection. As HBV and HCV have
shared transmission routes, dual infection is not an uncommon scenario, which is
associated with more advanced liver disease than either HBV or HCV mono
infection. Thus, there is a clear need to further understand the interaction
between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual
infection in order to devise effective therapy. This review summarizes the
current understanding of HBV/HCV dual infection, focusing on the pathobiological
role and therapeutic potential of miR-122.
PMID- 25848474
TI - Cirrhotic cardiomyopathy: Implications for the perioperative management of liver
transplant patients.
AB - Cirrhotic cardiomyopathy is a disease that has only recently been recognised as a
definitive clinical entity. In the setting of liver cirrhosis, it is
characterized by a blunted inotropic and chronotropic response to stress,
impaired diastolic relaxation of the myocardium and prolongation of the QT
interval in the absence of other known cardiac disease. A key pathological
feature is the persistent over-activation of the sympathetic nervous system in
cirrhosis, which leads to down-regulation and dysfunction of the beta-adrenergic
receptor. Diagnosis can be made using a combination of echocardiography (resting
and stress), tissue Doppler imaging, cardiac magnetic resonance imaging, 12-lead
electrocardiogram and measurement of biomarkers. There are significant
implications of cirrhotic cardiomyopathy in a number of clinical situations in
which there is an increased physiological demand, which can lead to acute cardiac
decompensation and heart failure. Prior to transplantation there is an increased
risk of hepatorenal syndrome, cardiac failure following transjugular intrahepatic
portosystemic shunt insertion and increased risk of arrhythmias during acute
gastrointestinal bleeding. Liver transplantation presents the greatest
physiological challenge with a further risk of acute cardiac decompensation. Peri
operative management should involve appropriate choice of graft and minimization
of large fluctuations in preload and afterload. The avoidance of cardiac failure
during this period has important prognostic implications, as there is evidence to
suggest a long-term resolution of the abnormalities in cirrhotic cardiomyopathy.
PMID- 25848475
TI - Recommendations for the use of chemoembolization in patients with hepatocellular
carcinoma: Usefulness of scoring system?
AB - Several hepatocellular carcinoma (HCC) staging systems have been established, and
a variety of country-specific treatment strategies are also proposed. The
barcelona - clinic liver cancer (BCLC) system is the most widely used in Europe.
The Hong Kong liver Cancer is a new prognostic staging system; it might become
the reference system in Asia. Transarterial chemoembolization (TACE) is the most
widely used treatment for HCC worldwide; but it showed a benefit only for
intermediate stage HCC (BCLC B), and there is still no consensus concerning
treatment methods and treatment strategies. In view of the highly diverse nature
of HCC and practices, a scoring system designed to assist with decision making
before the first TACE is performed or prior to repeating the procedure would be
highly useful.
PMID- 25848476
TI - Hepatitis C virus reinfection after liver transplant: New chances and new
challenges in the era of direct-acting antiviral agents.
AB - The first interferon-free regimens have been approved for the treatment of
patients with chronic hepatitis C virus (HCV). In the liver transplant (LT)
setting, these regimens are expected to have an important effect, because graft
loss due to HCV recurrence is a serious problem after LT. The response to the
hitherto conventional treatment with pegylated interferon and ribavirin is poor.
The significantly better response rates achieved with boceprevir-based and
telaprevir-based triple therapy have led to better graft and patient survival
rates, but severe drug interactions with immunosuppressants limit the feasibility
of this therapy for LT patients. With the approval of sofosbuvir in January 2014,
of simeprevir in May 2014, and of daclatasvir in August 2014, three antiviral
agents are now available and promise to be applicable without relevant adverse
effects or negative interactions with immunosuppressants. Thus, 2014 marks the
beginning of a new era of treatment options for HCV recurrence after LT. Although
safety and efficacy studies of several interferon-free regimens for patients with
HCV recurrence after LT have achieved good preliminary results, reports of
clinical experiences with LT patients are scarce. The lack of randomized studies,
the small number of enrolled and carefully selected patients, and the
heterogeneity of these studies make the results questionable. Real-life
experiences are eagerly awaited so that clinicians can estimate the usefulness
and the pitfalls of these new regimens. Additionally, the high costs of these
agents may limit their accessibility for many patients. The aim of this review is
to summarize the current experience with and the expectations of the new direct
acting antiviral agents for LT patients.
PMID- 25848477
TI - Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases:
When and how to apply prophylaxis, with a special focus on corticosteroid
therapy.
AB - Currently immunosuppressive and biological agents are used in a more extensive
and earlier way in patients with inflammatory bowel disease, rheumatic or
dermatologic diseases. Although these drugs have shown a significant clinical
benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV)
reactivations have been reported widely, even including liver failure and death,
and it represents a deep concern in these patients. Current guidelines recommend
to pre-emptive therapy in patients with immunosuppressants in general, but
preventive measures focused in patients with corticosteroids and inflammatory
diseases are scarce. Screening for HBV infection should be done at diagnosis. The
patients who test positive for hepatitis B surface antigen, but do not meet
criteria for antiviral treatment must receive prophylaxis before undergoing
immunosuppression, including corticosteroids at higher doses than prednisone 20
mg/d during more than two weeks. Tenofovir and entecavir are preferred than
lamivudine because of their better resistance profile in long-term
immunosuppressant treatments. There is not a strong evidence, to make a general
recommendation on the necessity of prophylaxis therapy in patients with
inflammatory diseases that are taking low doses of corticosteroids in short term
basis or low systemic bioavailability corticosteroids such as budesonide or
beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is
recommended, starting early antiviral therapy if DNA levels begin to rise. In
patients with occult or resolved hepatitis the risk of reactivation is much
lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.
PMID- 25848478
TI - Hepatitis C in hemodialysis patients.
AB - Despite reduction of hepatitis C prevalence after recognition of the virus and
testing of blood products, hemodialysis (HD) patients still comprise a high risk
group. The natural history of hepatitis C virus (HCV) infection in dialysis is
not fully understood while the clinical outcome differs from that of the general
population. HD patients show a milder liver disease with lower aminotransferase
and viral levels depicted by milder histological features on liver biopsy.
Furthermore, the "silent" clinical course is consistent with a slower disease
progression and a lower frequency of cirrhosis and hepatocellular carcinoma.
Potential explanations for the "beneficial" impact of uremia and hemodialysis on
chronic HCV infection are impaired immunosurveillance leading to a less
aggressive host response to the virus and intradialytic release of
"hepatoprotective" cytokines such as interferon (IFN)-alpha and hepatocyte growth
factor. However, chronic hepatitis C is associated with a higher liver disease
related cardiovascular and all-cause mortality of HD patients. Therapy is
indicated in selected patients groups including younger patients with low
comorbidity burden and especially renal transplant candidates, preferably after
performance of a liver biopsy. According to current recommendations, choice of
treatment is IFN or pegylated interferon with a reported sustained viral response
at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding
combination therapy with low doses of ribavirin which provide higher standard
variable rates and good safety results, offer another therapeutic option. The new
protease inhibitors may be the future for HCV infected HD patients, though data
are still lacking.
PMID- 25848479
TI - Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver
disease.
AB - Nonalcoholic fatty liver disease (NAFLD) is currently recognized as one of the
most common causes of chronic liver disease. It involves a spectrum of conditions
that include pure steatosis without inflammation, steatohepatitis, fibrosis and
cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance
that determines lipid accumulation in the hepatocytes and, thus, oxidative
stress, which is followed by inflammatory response. However, NAFLD pathogenesis
is still largely unknown and has been extensively investigated. Although life
style modification with the aim of losing weight has been advocated to treat this
disorder, its effectiveness is limited; additionally, there is no specific
pharmacologic treatment until nowadays. Recent evidence suggests that the gut
microbiota may play a role in the development of insulin resistance, hepatic
steatosis, necroinflammation and fibrosis. Differences in gut microbiota between
NAFLD patients and lean individuals as well as presence of small intestinal
bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some
data indicate that the immunoregulatory effects of probiotics may be beneficial
in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial
barrier function and strengthen the intestinal wall decreasing its permeability;
reduce bacterial translocation and endotoxemia; improve intestinal inflammation;
and reduce oxidative and inflammatory liver damage. In this article, we review
the clinical trials on the use of probiotics in the treatment of NAFLD and
discuss the effects of these agents and their efficacy as an emerging therapeutic
resource to treat NAFLD patients.
PMID- 25848480
TI - Treatment of hepatocellular carcinoma: Steps forward but still a long way to go.
AB - Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third
cause of tumor associated deaths worldwide. HCC incidence rates are increasing in
many parts of the world including developing and developed countries. Potentially
curative treatments for HCC are resection and liver transplantation, but these
are only suitable for patients with small tumors, meeting strict pre-defined
criteria, or well-compensated liver disease. Early diagnosis of HCC can be
achieved by surveillance of at-risk populations. For patients with non-resectable
disease treatments modalities include loco-ablative and systemic therapies. In
this review we focus on treatment options in HCC and their allocation. Although
significant research is in progress, to this date, the results are unsatisfactory
with limited long-term survival. In the fight against this deadly disease, there
is still a long way to go.
PMID- 25848481
TI - Role of diet on non-alcoholic fatty liver disease: An updated narrative review.
AB - The purpose of this article review is to update what is known about the role of
diet on non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common cause
of chronic liver disease in the developed world and is considered to be a
spectrum, ranging from fatty infiltration of the liver alone (steatosis), which
may lead to fatty infiltration with inflammation known as non alcoholic
steatohepatitis While the majority of individuals with risk factors like obesity
and insulin resistance have steatosis, only few people may develop
steatohepatitis. Current treatment relies on weight loss and exercise, although
various insulin-sensitizing medications appear promising. Weight loss alone by
dietary changes has been shown to lead to histological improvement in fatty liver
making nutrition therapy to become a cornerstone of treatment for NAFLD.
Supplementation of vitamin E, C and omega 3 fatty acids are under consideration
with some conflicting data. Moreover, research has been showed that saturated
fat, trans-fatty acid, carbohydrate, and simple sugars (fructose and sucrose) may
play significant role in the intrahepatic fat accumulation. However, true
associations with specific nutrients yet to be clarified.
PMID- 25848482
TI - Variations and mutations in the hepatitis B virus genome and their associations
with clinical characteristics.
AB - Hepatitis B virus (HBV) infection is major global issue, because chronic HBV
infection is strongly associated with liver cancer. HBV spread worldwide with
various mutations and variations. This variability, called quasispecies, is
derived from no proof-reading capacity of viral reverse transcriptase. So far,
thousands of studies reported that the variety of genome is closely related to
the geographic distribution and clinical characteristics. Recent technological
advances including capillary sequencer and next generation sequencer have made in
easier to analyze mutations. The variety of HBV genome is related to not only
antigenicity of HBs-antigen but also resistance to antiviral therapies.
Understanding of these variations is important for the development of diagnostic
tools and the appropriate therapy for chronic hepatitis B. In this review, recent
publications in relation to HBV mutations and variations are updated and
summarized.
PMID- 25848483
TI - Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy.
AB - Oxidative stress has been investigated in the context of alcoholic liver injury
for many years and shown to be a causal factor of chronic hepatitis C (CHC),
nonalcoholic steatohepatitis (NASH), drug-induced liver injury, Wilson's disease,
and hemochromatosis. In CHC, it has been demonstrated that oxidative stress plays
an important role in hepatocarcinogenesis. In cases with persistent hepatitis due
to failure of hepatitis C virus eradication, or chronic liver disease, such as
NASH, the treatment of which remains unestablished, it is important to reduce
serum alanine aminotransferase levels and prevent liver fibrosis and development
of hepatocellular carcinoma. This also suggests the importance of antioxidant
therapy. Among treatment options where it would be expected that anti
inflammatory activity plays a role in their confirmed efficacy for chronic
hepatitis, iron depletion therapy, glycyrrhizin, ursodeoxycholic acid, Sho-Saiko
To, and vitamin E can all be considered antioxidant therapies. To date, however,
the ability of these treatments to prevent cancer has been confirmed only in CHC.
Nevertheless, anti-inflammatory and anti-fibrotic effects have been demonstrated
in other liver diseases and these therapies may potentially be effective for
cancer prevention.
PMID- 25848484
TI - Occult hepatitis B virus infection and blood transfusion.
AB - Transfusion-transmitted infections including hepatitis B virus (HBV) have been a
major concern in transfusion medicine. Implementation of HBV nucleic acid testing
(NAT) has revealed occult HBV infection (OBI) in blood donors. In the mid-1980s,
hepatitis B core antibody (HBc) testing was introduced to screen blood donors in
HBV non-endemic countries to prevent transmission of non-A and non-B hepatitis.
That test remains in use for preventing of potential transmission of HBV from
hepatitis B surface antigen (HBsAg)-negative blood donors, even though anti
hepatitis C virus tests have been introduced. Studies of anti-HBc-positive donors
have revealed an HBV DNA positivity rate of 0%-15%. As of 2012, 30 countries have
implemented HBV NAT. The prevalence of OBI in blood donors was estimated to be
8.55 per 1 million donations, according to a 2008 international survey. OBI is
transmissible by blood transfusion. The clinical outcome of occult HBV
transmission primarily depends on recipient immune status and the number of HBV
DNA copies present in the blood products. The presence of donor anti-HBs reduces
the risk of HBV infection by approximately five-fold. The risk of HBV
transmission may be lower in endemic areas than in non-endemic areas, because
most recipients have already been exposed to HBV. Blood safety for HBV, including
OBI, has substantially improved, but the possibility for OBI transmission
remains.
PMID- 25848487
TI - Survival rates according to barcelona clinic liver cancer sub-staging system
after transarterial embolization for intermediate hepatocellular carcinoma.
AB - AIM: To investigate the survival rates after transarterial embolization (TAE).
METHODS: One hundred third six hepatocellular carcinoma (HCC) patients [90
barcelona clinic liver cancer (BCLC) B] were submitted to TAE between August 2008
and December 2013 in a single center were retrospectively studied. TAE was
performed via superselective catheterization followed by embolization with
polyvinyl alcohol or microspheres. The date of the first embolization until death
or the last follow-up date was used for the assessment of survival. The survival
rates were calculated using the Kaplan-Meier method, and the groups were compared
using the log-rank test. RESULTS: The overall mean survival was 35.8 mo (95%CI:
25.1-52.0). The survival rates of the BCLC A patients (33.7%) were 98.9%, 79.0%
and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo
(95%CI: 27.5-52.0). The survival rates of the BCLC B patients (66.2%) were 89.0%,
69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0
mo (95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging
showed significant differences between the groups, with mean survival rates in
the B1, B2, B3 and B4 groups of 33.5 mo (95%CI: 32.8-34.3), 28.6 mo (95%CI: 27.5
29.8), 19.0 mo (95%CI: 17.2-20.9) and 13 mo, respectively (P = 0.013).
CONCLUSION: The BCLC sub-staging system could add additional prognosis
information for post-embolization survival rates in HCC patients.
PMID- 25848485
TI - Staging of liver fibrosis or cirrhosis: The role of hepatic venous pressure
gradient measurement.
AB - Liver fibrosis is a common histological change of chronic liver injury and it is
closely related with portal hypertension which is hemodynamic complication of
chronic liver disease. Currently, liver fibrosis has been known as a reversible
dynamic process in previous literatures. Although liver biopsy is a gold standard
for assessing the stage of liver fibrosis, it may not completely represent the
stage of liver fibrosis because of sampling error or semi-quantative measurement.
Recent evidences suggested that histologic, clinical, hemodynamic, and biologic
features are closely associated in patients with chronic liver disease. Hepatic
venous pressure gradient (HVPG) measurement has been known as a modality to
evaluate the portal pressure. The HVPG measurement has been used clinically for
fibrosis diagnosis, risk stratification, preoperative screening for liver
resection, monitoring the efficacy of medical treatments, and assessing the
prognosis of liver fibrosis. Therefore, the HVPG measurement can be used to
monitor areas the chronic liver disease but also other important areas of chronic
liver disease.
PMID- 25848488
TI - Unusual presentation of severely disseminated and rapidly progressive hydatic
cyst: Malignant hydatidosis.
AB - The infection caused by the tapeworm Echinococcus granulosus leads to the
development of hydatic disease. It is the most frequent mediterranean parasitic
infection that commonly affects the liver and rarely involves multiple organs.
Herein, we report an exceptional and confusing presentation of hepatopulmonary
and splenic hydatidosis due to Echinococcus granulosus that caused diagnostic
problems occuring in a 70-year-old man, treated with chemotherapy, with favorable
outcome. This was a very unusual case of disseminated hydatid cyst highlighting
the interest of keeping a high level of clinical suspicion of this diagnosis
every time we have a cystic lesion of the liver.
PMID- 25848486
TI - Evidence-based consensus on the diagnosis, prevention and management of hepatitis
C virus disease.
AB - Hepatitis C virus (HCV) is a potent human pathogen and is one of the main causes
of chronic hepatitis round the world. The present review describes the evidence
based consensus on the diagnosis, prevention and management of HCV disease.
Various techniques, for the detection of anti-HCV immunoglobulin G immunoassays,
detection of HCV RNA by identifying virus-specific molecules nucleic acid
testings, recognition of core antigen for diagnosis of HCV, quantitative antigen
assay, have been used to detect HCV RNA and core antigen. Advanced technologies
such as nanoparticle-based diagnostic assays, loop-mediated isothermal
amplification and aptamers and Ortho trak-C assay have also come to the front
that provides best detection results with greater ease and specificity for
detection of HCV. It is of immense importance to prevent this infection
especially among the sexual partners, injecting drug users, mother-to-infant
transmission of HCV, household contact, healthcare workers and people who get
tattoos and piercing on their skin. Management of this infection is intended to
eradicate it out of the body of patients. Management includes examining the
treatment (efficacy and protection), assessment of hepatic condition before
commencing therapy, controlling the parameters upon which dual and triple
therapies work, monitoring the body after treatment and adjusting the co-factors.
Examining the treatment in some special groups of people (HIV/HCV co-infected,
hemodialysis patients, renal transplanted patients).
PMID- 25848489
TI - Colorectal cancer risk in hamartomatous polyposis syndromes.
AB - Colorectal cancer (CRC) is a major cause of morbidity and mortality around the
world, and approximately 5% of them develop in a context of inherited mutations
leading to some form of familial colon cancer syndromes. Recognition and
characterization of these patients have contributed to elucidate the genetic
basis of CRC. Polyposis Syndromes may be categorized by the predominant
histological structure found within the polyps. The aim of the present paper is
to review the most important clinical features of the Hamartomatous Polyposis
Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers
syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan
Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in
order to retrieve the most recent and important papers (articles, reviews,
clinical cases and clinical guidelines) regarding the studied subject. We
searched for terms such as "hamartomatous polyposis syndromes", "Peutz-Jeghers
syndrome", "juvenile polyposis syndrome", "juvenile polyp", and "PTEN hamartoma
tumour syndrome" (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article
reports the wide spectrum of disease severity and extraintestinal manifestations,
with a special focus on their potential to develop colorectal and other
neoplasia. In the literature, the reported colorectal cancer risk for Juvenile
Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57%
and 18%, respectively. A review regarding cancer surveillance recommendations is
also presented.
PMID- 25848490
TI - Long-term survival following radiofrequency ablation of colorectal liver
metastases: A retrospective study.
AB - AIM: To retrospectively evaluate the long-term survival of patients that received
radiofrequency ablation (RFA) therapies of colorectal liver metastases. METHODS:
In 2005 to 2008, RFA of 105 colorectal liver metastases (CRLM) were performed on
49 patients in our institution. The liver metastases were evaluated, both before
and after ablation therapies, with contrast enhanced computerised tomography and
contrast enhanced ultrasonography. Histological evidence of malignant liver
metastases was obtained in the few instances where contrast enhanced
ultrasonography gave equivocal results. Accesses to the CRLM were guided
ultrasonically in all patients. The data obtained from records of these ablations
were retrospectively analysed and survival data were compared with existing
studies in the literature. RESULTS: 1-, 2-, 3-, 4- and 5-year survival rates,
when no stringent selection criteria were applied, were 92%, 65%, 51%, 41% and
29% respectively. To explore the impact of the number and size of CRLM on
patients' survival, an exclusion of 13 patients (26.5%) with number of CRLM >= 5
and tumour size >= 40 mm resulted in 1-, 2-, 3-, 4- and 5-year survival rates
improving to 94%, 69%, 53%, 42% and 31% respectively. It is of note that 9 of 49
patients developed extra-hepatic metastases, not visible or seen on pre-treatment
scans, just after RFA treatment. These patients had poorer survival. The
development of extra-hepatic metastases in nearly 20% of the patients included in
our study can partly account for modestly lower survival rates as compared with
earlier studies in the literature. CONCLUSION: Our study underscores the fact
that optimum patients' selection before embarking on RFA treatment is vitally
important to achieving a superior outcome.
PMID- 25848491
TI - Respiratory distress due to malignant ascites palliated by hyperthermic
intraperitoneal chemotherapy.
AB - Malignant ascites is a common symptom in patients with peritoneal cancer. Current
assumption is that an increased vascular permeability and obstruction of
lymphatic channels lead to the accumulation of fluid in the abdominal cavity.
This case report describes a severely symptomatic patient with malignant ascites.
The previously healthy 73-year-old male was presented with abdominal distention
causing respiratory distress. Computed tomography revealed large amounts of
ascites, a recto-sigmoidal mass with locoregional lymphadenopathy and an omental
cake. Biopsy taken during colonoscopy revealed an adenocarcinoma of the colon
with signet cell differentiation. A widespread peritoneal carcinomatosis was
found during a diagnostic laparoscopy. The extent of peritoneal disease rendered
the patient not suitable for cytoreductive surgery with curative intent. The
ascites proved to be refractory to ultrasound-guided paracentesis; thus, a
decision was made to perform palliative hyperthermic intraperitoneal chemotherapy
without cytoreductive surgery. Consequently, ascites production stopped, and the
respiratory distress was relieved thereafter. The postoperative recovery was
uneventful. Ascites recurred eight months later, and a second hyperthermic
intraperitoneal chemotherapy procedure was performed. The patient was still alive
at the time of writing, 16 mo after the initial diagnosis.
PMID- 25848492
TI - Successful emergency resection of a massive intra-abdominal hemophilic
pseudotumor.
AB - An intra-abdominal pseudotumor is a rare complication of hemophilia. Surgical
treatment is associated with high morbidity and mortality rates and reported
cases are scarce. We present a 66-year-old Caucasian male suffering from severe
hemophilia type A treated for 10 years with Factor VIII. Major complications from
the disease were chronic hepatitis B and C, cerebral hemorrhage and disabling
arthropathy. Twenty-three years ago, retro-peritoneal bleeding led to the
development of a large intra-abdominal pseudotumor, which was followed-up
clinically due to the high surgical risk and the lack of clinical indication. The
patient presented to the emergency department with severe sepsis and umbilical
discharge that had appeared over the past two days. Abdominal computed tomography
images were highly suggestive of a bowel fistula. The patient was taken to the
operating room under continuous infusion of factor VIII. Surgical exploration
revealed a large infected pseudotumor with severe intra-abdominal adhesions and a
left colonic fistula. The pseudotumor was partially resected en bloc with the
left colon leaving the posterior wall intact. The postoperative period was
complicated by septic shock and a small bowel fistula that required reoperation.
He was discharged on the 73(rd) hospital day and is well 8 mo after surgery. No
bleeding complications were encountered and we consider surgery safe under factor
VIII replacement therapy.
PMID- 25848493
TI - Incarcerated amyand hernia.
AB - Amyand's hernia is a rare condition defined by the inclusion of the appendix
vermiformis within the hernia sac. Its incidence among cases of groin hernia is
less than 1%. The clinical manifestation of incarcerated inguinal hernia
generally masks the symptoms and signs of acute appendicitis, which renders
preoperative diagnosis difficult. In this study, we present two cases of Amyand's
hernia that were diagnosed preoperatively. The patients were taken for operation
with the prediagnosis of incarcerated inguinal hernia. We evaluated these cases
along with data from prior studies.
PMID- 25848494
TI - Communication of brain network core connections altered in behavioral variant
frontotemporal dementia but possibly preserved in early-onset Alzheimer's
disease.
AB - Diffusion imaging and brain connectivity analyses can assess white matter
deterioration in the brain, revealing the underlying patterns of how brain
structure declines. Fiber tractography methods can infer neural pathways and
connectivity patterns, yielding sensitive mathematical metrics of network
integrity. Here, we analyzed 1.5-Tesla whole-brain diffusion-weighted images from
64 participants - 15 patients with behavioral variant frontotemporal dementia
(bvFTD), 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly
controls. Using whole-brain tractography, we reconstructed structural brain
connectivity networks to map connections between cortical regions. We evaluated
the brain's networks focusing on the most highly central and connected regions,
also known as hubs, in each diagnostic group - specifically the "high-cost"
structural backbone used in global and regional communication. The high-cost
backbone of the brain, predicted by fiber density and minimally short pathways
between brain regions, accounted for 81-92% of the overall brain communication
metric in all diagnostic groups. Furthermore, we found that the set of pathways
interconnecting high-cost and high-capacity regions of the brain's communication
network are globally and regionally altered in bvFTD, compared to healthy
participants; however, the overall organization of the high-cost and high
capacity networks were relatively preserved in EOAD participants, relative to
controls. Disruption of the major central hubs that transfer information between
brain regions may impair neural communication and functional integrity in
characteristic ways typical of each subtype of dementia.
PMID- 25848495
TI - Enhanced semiempirical QM methods for biomolecular interactions.
AB - Recent successes and failures of the application of 'enhanced' semiempirical QM
(SQM) methods are reviewed in the light of the benefits and backdraws of adding
dispersion (D) and hydrogen-bond (H) correction terms. We find that the accuracy
of SQM-DH methods for non-covalent interactions is very often reported to be
comparable to dispersion-corrected density functional theory (DFT-D), while
computation times are about three orders of magnitude lower. SQM-DH methods thus
open up a possibility to simulate realistically large model systems for problems
both in life and materials science with comparably high accuracy.
PMID- 25848496
TI - Role of P2X7 and P2Y2 receptors on alpha-secretase-dependent APP processing:
Control of amyloid plaques formation "in vivo" by P2X7 receptor.
AB - Amyloid precursor protein (APP) is expressed in a large variety of neural and non
neural cells. The balance between non-pathogenic and pathologic forms of APP
processing, mediated by alpha-secretase and beta-secretase respectively, remains
a crucial step to understand beta-amyloid, Abeta42 peptide, formation and
aggregation that are at the origin of the senile plaques in the brain, a
characteristic hallmark of Alzheimer's disease (AD). In Neuro-2a, a neuroblastoma
cell line that constitutively expresses APP, activation of the P2X7 receptor
leads to reduction of alpha-secretase activity, the opposite effect being
obtained by P2Y2 receptor activation. The in vivo approach was made possible by
the use of J20 mice, a transgenic mouse model of familial Alzheimer's disease
(FAD) expressing human APP mutant protein. This animal exhibits prominent amyloid
plaques by six months of age. In vivo inhibition of the P2X7 receptor induced a
significant decrease in the number and size of hippocampal amyloid plaques. This
reduction is mediated by an increase in the proteolytic processing of APP through
alpha-secretase activity, which correlates with an increase in the phosphorylated
form of GSK-3, a less active form of this enzyme. The in vivo findings
corroborate the therapeutic potential of P2X7 antagonists in the treatment of
FAD.
PMID- 25848498
TI - Genotyping of carbapenem resistant Acinetobacter baumannii isolated from tracheal
tube discharge of hospitalized patients in intensive care units, Ahvaz, Iran.
AB - BACKGROUND AND OBJECTIVES: Carbapenem resistant A. baumannii is an emerging cause
of nosocomial infections. The aims of this study were identification of the most
prevalent of carbapenem resistant genes, molecular typing and antimicrobial
evaluation of A.baumannii in intensive care units. MATERIALS AND METHODS: Two
hundred and six A. baumannii were isolated from tracheal tube discharge of
hospitalized patients at different intensive care units in Ahvaz, Iran.
Antimicrobial susceptibility test was done on all isolates. Multiplex and
singleplex PCR were performed for detection of bla OXA-23-like, bla OXA-24-like,
bla OXA-51-like, bla OXA-58-like, bla VIM, bla IMP, bla SPM and bla NDM genes.
Genetic relationship of all isolates was determined by REP-PCR method. RESULTS:
Out of 206 examined isolates, 198 (96.1%) isolates were resistant to imipenem and
meropenem. However 3.9% isolates were sensitive to these antibiotics. The bla OXA
23-like and bla OXA-24-like genes were detected in 85% and 8.7% of strains,
respectively. No bla OXA-58- like, bla IMP, bla VIM, bla SPM and bla NDM were
detected. REP-PCR results showed that isolates were belonged to five genotypes:
Genotype A was the most prevalent (P- value < 0.001): it was observed in 75 of
206 strains (36.4%). Genotype B, and C were found in 28.6% and 27.7%,
respectively. The rate of other genotypes was as follows: D (2.4%), E (1%).
CONCLUSION: Based on the obtained results, the rate of carbapenem resistance was
high among of A. baumannii which was isolated from intensive care units patients
and oxacillinase genes were the most prevalent carbapenem resistant genes. These
results revealed that three clones, A, B and C of A.baumannii are common in our
hospitals.
PMID- 25848499
TI - Multidrug resistant Gram-negative bacilli in lower respiratory tract infections.
AB - BACKGROUND: Lower respiratory tract infections are among important causes of
morbidity and mortality for all age groups. The emergence of multidrug resistant
Gram-negative bacilli is an issue of increasing concern. MATERIALS AND METHODS: A
retrospective study including respiratory specimens (sputum and BAL) was
conducted in our tertiary care centre. Samples were processed for microscopy,
culture and susceptibility testing following standard methods. Multidrug
resistant Gram-negative bacilli causing lower respiratory tract infections were
studied for their causation of disease. The effect of appropriate treatment on
clinical outcome was observed. RESULTS: A total of 472 Gram-negative pathogens
were isolated from sputum and broncho-alveolar lavage fluid specimens during the
study period. Among these Gram-negative pathogens 175 (37%) were found to be
multidrug resistant. Klebsiella pneumoniae 85 (48.6%) and Acinetobacter spp. 59
(33.7%) were the predominant multidrug resistant Gram-negative bacilli isolated.
Based on clinico-microbiological correlation, 138 (78.9%) multidrug resistant
isolates were found to be pathogenic and the rest 37 (21.1%) were considered as
colonizers. After initiating appropriate antibiotic therapy, clinical improvement
was seen in 110 (79.7%) patients. In the patients who showed improvement,
amikacin (34.3%) and cefoperazone-sulbactum (21.8%) were found to be the most
effective drugs. CONCLUSION: A large majority of the isolated multidrug resistant
Gram-negative bacilli were found to be pathogenic. Regular surveillance which
directs appropriate empirical therapy; and good clinic-microbiological workup of
each case of lower respiratory tract infection can reduce the morbidity and
mortality associated with multidrug resistant organisms.
PMID- 25848497
TI - Biochemical functional predictions for protein structures of unknown or uncertain
function.
AB - With the exponential growth in the determination of protein sequences and
structures via genome sequencing and structural genomics efforts, there is a
growing need for reliable computational methods to determine the biochemical
function of these proteins. This paper reviews the efforts to address the
challenge of annotating the function at the molecular level of uncharacterized
proteins. While sequence- and three-dimensional-structure-based methods for
protein function prediction have been reviewed previously, the recent trends in
local structure-based methods have received less attention. These local structure
based methods are the primary focus of this review. Computational methods have
been developed to predict the residues important for catalysis and the local
spatial arrangements of these residues can be used to identify protein function.
In addition, the combination of different types of methods can help obtain more
information and better predictions of function for proteins of unknown function.
Global initiatives, including the Enzyme Function Initiative (EFI), COMputational
BRidges to EXperiments (COMBREX), and the Critical Assessment of Function
Annotation (CAFA), are evaluating and testing the different approaches to
predicting the function of proteins of unknown function. These initiatives and
global collaborations will increase the capability and reliability of methods to
predict biochemical function computationally and will add substantial value to
the current volume of structural genomics data by reducing the number of absent
or inaccurate functional annotations.
PMID- 25848500
TI - Molecular evaluations of extended spectrum beta-lactamase producing strains of
Serratia isolated from blood samples of the patients in Namazi Hospital, Shiraz,
Southern Iran.
AB - BACKGROUND AND OBJECTIVE: Nowadays, the presence of extended-spectrum beta
lactamases (ESBLs) producing strains in Serratia genus causes the emergence of
resistance to many antibiotics. So, the lack of proper diagnosis of ESBLs strains
can lead to failure in the treatment. The objective of the present study was to
investigate ESBLs production in Serratia strains isolated from the clinical blood
samples in Shiraz, Iran. MATERIALS AND METHODS: In this study, 39 Serratia
strains isolated from the patients referred to Namazi Hospital, during a 2 year
period were tested. The antimicrobial resistance of the isolates to 21
antibiotics was evaluated using Kirby-Bauer disk diffusion method. Combination
disk method was used to determine the ESBL phenotype among the isolates. PCR was
performed to investigate the presence of ESBL genes of SHV, OXA and TEM types.
RESULTS: The lowest antibiotic resistance rates belonged to meropenem (7.69%) and
imipenem (5.12%). Overall, positive ESBL phenotype was identified in 69% (n = 27)
of the isolates, 70.37% (n = 19) for S. marcescens and 29.62% (n = 8) for S.
liquefaciens. Results obtained by PCR showed that only 20.51% carried OXA gene
and 15.38% carried SHV-1 gene. TEM gene was detected in none of the isolates.
CONCLUSION: This study showed a high prevalence of the emerging ESBL producing
strains among clinical isolates of Serratia that could lead to an increase in
antibiotic resistance. However, ESBLs genes other than those tested here may be
more responsible for the emergence of ESBL phenotype among Serratia clinical
isolates in our region.
PMID- 25848501
TI - Magnitude of drug resistant shigellosis in Nepalese patients.
AB - BACKGROUND AND OBJECTIVES: Shigella plays an important role as a causative
organism of acute gastroenteritis, in children and others. Rapid emergence of
antibiotic resistance warrants continuous monitoring of susceptibility pattern of
bacterial isolates. We report here our findings about Shigella spp. isolates and
their drug resistance patterns in Nepalese patients. MATERIALS AND METHODS: The
study was conducted on 507 Nepalese patients with acute gastroenteritis attending
outpatient and inpatient departments of Nepalgunj Medical college and teaching
Hospital, Banke, Nepal from September 2011 to April 2013. Stool specimens were
processed for isolation and identification of Shigella species following the
standard microbiological methods while the disc diffusion test was used to
determine antimicrobial resistance patterns of the recovered isolates at the
central Laboratory of Microbiology. RESULTS: Sixty nine isolates were identified
as Shigella species. S. flexneri, S. dysenteriae, S. boydii and S. sonnei
accounted, respectively, for 42.03%, 27.54%, 21.74% and 8.70% of the total number
of Shigella isolates. Resistance to nalidixic acid (95.65%), ampicillin (85.51%),
co-trimoxazole (82.61%) and ciprofloxacin (47.83%) was observed. Among 69
isolates, 29 (42.03%) were from children aged 1-10 years and this group was
statistically significant (P < 0.05), compared to the other age groups.
CONCLUSIONS: The study revealed endemicity of shigellosis with S. flexneri as the
predominant serogroup in Nepalese patients. Children were at a higher risk of
severe shigellosis. Nalidixic acid, ampicillin, co-trimoxazole and ciprofloxacin
should not be used empirically as the first line drugs in treatment of
shigellosis. Continuous local monitoring of resistance patterns is necessary for
the appropriate selection of empirical antimicrobial therapy.
PMID- 25848502
TI - Conventional and molecular investigation of Shigella isolates in relation to an
outbreak in the area of Isfahan, Iran.
AB - BACKGROUND AND OBJECTIVE: Over 165 million cases of shigellosis occur in the
world each year, mostly in developing countries. Outbreaks of shigellosis are
associated with poor sanitation, natural calamities, contaminated food and
crowded living conditions. In late summer 2006, during the final stage of an
outbreak of shigellosis at a vast region of Isfahan province, Naein & Ardestan,
our laboratory was assigned to investigate the outbreak in order to determine the
causative agent. MATERIALS AND METHODS: A total of 146 rectal swabs which had
been collected from the patients by local laboratories on separate days were
screened using a battery of conventional and molecular tests. RESULTS: Thirteen
specimens tested positive for Shigella spp. They were identified as S. sonnei (6,
46.1%), S. dysenteriae (4, 30.8%), S. flexneri (2, 15.4%) and Shigella spp (1,
7.7%) by conventional and molecular microbiological tests. According to
ribotyping results the isolates were grouped into 3 distinct clusters
encompassing the majority of isolates and a single line of descent representing
isolate S122 which was nonreactive with any Shigella polyvalent antisera.
CONCLUSION: This diarrheal outbreak appeared to be the result of shigellosis.
Despite the fact that Shigella sonnei was the predominant organism isolated from
patients, the causative agent of outbreak diarrhea remains obscure, since other
Shigella species were also involved. The serologic testing supports this
conclusion, as do the molecular patterns of the Shigella isolates. Having
considered the time of investigation which was in the late stage of the outbreak,
it was very likely that a collection of endemic and epidemic clinical samples was
screened resulting in isolation of various Shigella species.
PMID- 25848503
TI - Genetic evaluation of Locus of enterocyte effacement pathogenicity island (LEE)
in Enteropathogenic Escherichia coli isolates (EPEC).
AB - BACKGROUND AND OBJECTIVES: Enteropathogenic Escherichia coli (EPEC) divided into
two groups typical and atypical (aspect). The main virulence genes are located in
a pathogenicity island called LEE (Locus of Enterocyte Effacement). LEE
frequently inserted in tRNA genes of selC, pheU and pheV in the bacterial
chromosome. tEPEC and aEPEC strains have some differences in their pathogenicity.
The purpose of this was to investigate the possible differences between tEPEC and
aEPEC strains according to the virulence genes encoding by LEE and their relation
to insertion sites. MATERIALS AND METHODS: In this study 130 E. coli isolates
confirmed by biochemical analysis from diarrheal patients, were evaluated for
EPEC pathotype by PCR. All EPEC strains tested for presence of some LEE encoded
virulence genes and sites of LEE insertion by PCR method. RESULTS: Among 50
strains of EPEC 28 (56%) and 22 (44%) were typical and atypical strains
respectively. 19 strains (30%) showed insertion in selC, 7 (14%) in pheU, 4 (8%)
in pheV, 8 (16%) in pheU and pheV, 1 (2%) in selC and pheU, 6 (12%) in pheV, pheU
and selC and 5 (10%) had no insertion in these sites. Moreover, spa (n = 8, 16%),
espB (n = 16, 32%), espD (n = 18, 36%), espF (n = 8, 16%), espG (n = 13, 26%),
espH (n = 12, 24%), map (n = 11, 32%) and tir (n = 4, 8%) were present among the
strains. CONCLUSION: Results showed that most of the virulence genes are present
in tEPEC isolates. However, aEPEC isolates may acquire other virulence factors.
The majority of tEPEC strains showed insertion at selC and aEPEC strains in pheV
and pheU.
PMID- 25848504
TI - Construction of a Baculovirus vector containing A subunit of Shiga toxin for
protein delivery.
AB - BACKGROUND AND OBJECTIVES: Baculovirus can be used as a vector in gene delivery
system. Viral envelope of baculovirus would display expressed protein/peptide and
it could render as a potential vaccine delivery system. In this regard, the gene
coding for A subunit of shiga toxin (StxA) from Escherichia coli (E. coli) strain
was cloned in a baculovirus expression system. StxA subunit has the ability to
inhibit protein synthesis and this ability applied in cancer therapy. In this
study, expression of StxA in baculovirus as a protein delivery system was
assessed in vitro. MATERIAL AND METHODS: StxA gene was cloned in pTriExTM
multisystem expression vector. This vector enables the protein expression in
multisystem, E. coli and baculovirus. This construct was used to express the gene
in E. coli and baculovirus. The construct containing StxA gene was made in
baculovirus and expression was confirmed, then baculovirus expressing STXA
transfect HeLa cells. RESULTS: The expression of STXA peptide (32kDa) was
confirmed by SDS-PAGE and western blotting in both expression systems. The A
subunit challenge to human cell Lines was applied as a delivery system by
baculoviruses. On the other hand, the inhibition of cell proliferation was also
demonstrated by baculovirus containing STXA subunit. CONCLUSION: STXA peptide
expression in baculovirus was shown in E. coli and baculovirus expression system.
Furthermore, it was shown that A subunit of Shiga toxin delivered by baculovirus
can inhibit cell proliferation in HeLa cells and leading to cell death.
Therefore, this prototype system could be a promising model for in vivo cancer
therapy and targeted protein delivery system.
PMID- 25848505
TI - Screening of soil actinomyectes against Salmonella serovar Typhi NCTC 5761 and
characterization of the prominent active strains.
AB - BACKGROUND AND OBJECTIVES: Annual incidence of infection with S. Typhi is
estimated to be about 17 million cases worldwide. A systematic search among
actinomycete isolates from soil of Iran aimed at finding active actinomycetes
against the causative agent of typhoid fever, Salmonella Typhi was carried out
during this study. MATERIALS AND METHODS: Our anti-Salmonella screening program
resulted in nine highly active actinomycete isolates. All nine antibiotic
producing strains showed broad-spectrum antibacterial activity, as five strains
showed antifungal activity as well. Based on microscopic morphology and cell wall
analysis, all nine active actinomycete strains were representatives of the genus
Streptomyces. Three of the producing strains including the isolates HG87, HG116
and HG443 with inhibition zone of >20 mm, were selected for further
identification and investigation of cytotoxic effects. RESULTS AND CONCLUSION:
None of the producing strains showed cytotoxicity on HEK and USSC cell lines,
while strain HG116 showed excellent antitumor activity on T47D cancer cell lines.
Isolates HG87, HG116 and HG443 can be distinguished from the related species by
some phenotypic and biochemical characteristics. Our results demonstrate the
broad-range biological activity exhibited by bioactive compounds of soil
actinomycetes from Iran.
PMID- 25848507
TI - Cloning, expression and purification of Mycobacterium tuberculosis ESAT-6 and CFP
10 antigens.
AB - BACKGROUND AND OBJECTIVES: ESAT-6 (6-kDaearly secretory antigenic target) and CFP
10 (10-kDa culture filtrate protein) have been described as dominant antigens
recognized by T-cells and considered as virulence factors in Mycobacterium
tuberculosis. The aim of this study was to clone, express and purify recombinant
ESAT-6 andCFP-10 proteins of M. tuberculosis in soluble form. MATERIALS AND
METHODS: ESAT-6 andCFP-10 genes were amplified by PCR, cloned into pET32a (+)
vector, and overexpress-ed using isopropyl-beta-D-thiogalactopyranoside in E.
coli BL21 (DE3). ESAT-6 andCFP-10 proteins were purified by Ni-NTA affinity
chromatography and were detected by anti- ESAT-6 and anti -CFP-10 antibodies.
RESULTS: ESAT-6 andCFP-10 genes were successfully expressed and purified. Anti-
ESAT-6 and anti-CFP-10 antibodies were produced after induction of immunization
against purified ESAT-6 andCFP-10 proteins in rabbit. CONCLUSION: In this study,
we cloned, expressed and purified sufficient amounts of ESAT-6 andCFP-10 and it
would be tested for the development of diagnostic kit for M. tuberculosis in
future.
PMID- 25848506
TI - Molecular diversity of Mycobacterium tuberculosis strains indifferent provinces
of Iran.
AB - BACKGROUND AND OBJECTIVES: Molecular epidemiology tools are widely used in
determining epidemiology of tuberculosis. Spoligotyping is a molecular
epidemiology method that is used for characterization and typing of Mycobacterium
tuberculosis complex strains. The method is based on polymorphism of the
chromosomal DR locus consisting of identical 36-bp DRs alternating with 35-41
unique spacers. The objective of this study was to investigate the prevalence of
M. tuberculosis spoligotypes in different provinces of Iran. MATERIALS AND
METHODS: M. tuberculosis strains were isolated from TB patients of
Mycobacteriology Research center (MRC). DNA was extracted from patient's clinical
samples. PCR was performed by using of specific primers for DR region. The
amplified DNA was hybridized to the spoligotyping Membrane. Hybridized DNA was
detected with ECL detection kit and by exposing ECL Hyperfilm to the membrane.
The obtained result was entered to a binary format and was analyzed using SpolDB4
database. RESULTS: Spoligotyping resulted in 136 different patterns. Out of 1242
M. tuberculosis strains, 1165 strains (93.8%) were classified into 59 clusters
and the remaining strains (6.2 %) were singleton. CONCLUSIONS: The results of
present study showed that strains of CAS family were more prevalent than other
strains in Iran. Other prevalent families were Haarlem, T and Beijing,
respectively.
PMID- 25848508
TI - Comparison of four different culture media for growth of Mycobacterium avium
subsp. avium isolated from naturally infected lofts of domestic pigeons.
AB - BACKGROUND AND OBJECTIVES: Diagnosis of avian tuberculosis by conventional
culture method is still considered as the "gold standard" technique. The main
objective of this study was to compare growth of Mycobacterium avium subsp. avium
on four specific Mycobacterial cultures such as glycerinated Lowenstein-Jensen
medium, pyruvate-enriched Lowenstein-Jensen medium, mycobactin J-supplemented
Herrold-egg yolk medium and plain Herrold-egg yolk medium. MATERIALS AND METHODS:
Eighty out of more than 600 pigeons were selected based on their clinical signs
and poor health conditions. The birds were numbered and their clinical signs were
registered in the working sheets, and under standard condi-tion, euthanized,
subjecting to necropsy examinations, followed by bacterial culture on four
specific media for Mycobacterium avium subsp. avium, including glycerinated
Lowenstein-Jensen (LJG) medium, pyruvate-enriched Lowenstein-Jensen medium (LJP),
mycobactin J-supplemented Herrold-egg yolk medium and plain Herrold-egg yolk
medium. RESULTS: Fifty one Mycobacterium avium subsp. avium were isolated from
pigeons. Mycobactin J-supplemented Herrold-egg yolk media yielded greater number
of colonies in shorter incubation time in compare with other media. CONCLUSION:
It was concluded that most of the isolates need mycobactin as a growth factor.
PMID- 25848509
TI - Evaluation of FLASH - PCR forrapid detection of Mycobacterium tuberculosis from
clinical specimens.
AB - BACKGROUND AND OBJECTIVES: Tuberculosis (TB) is the oldest known bacterial
disease in humans. Due to the rise of morbidity in recent years, early diagnosis
of the disease is necessary. MATERIALS AND METHODS: In this study we used
Fluorescent Amplification-Based Specific Hybridization (FLASH) PCR to
targetIS6110 for rapid detection of M. tuberculosis (MTB). To investigate the
important factors influencing the risk of TB, data from patients and their
medical records were analyzed. RESULT: The sensitivity and specificity of FLASH
PCR for detecting MTB were determined as 93.33% and 92.5%, respectively. The
findings of this study have suggested that removal of the contaminants in FLASH
PCR sign ificantly reduced the detection time, and MTB was much more rapidly
detected in the clinical specimens compared to the conventional culture and smear
examination. Results of the medical survey showed that the majority of TB
patients were males, over 51 years old, smokers, with pulmonary TB and normal
chest X-ray (CXR). CONCLUSION: MTB can be rapidly detected inclinical specimens
using FLASH-PCR in comparison with culture and smear examination.
PMID- 25848510
TI - Microbiological tests to identify a link between periodontitis and acute
myocardial infarction-an original research.
AB - BACKGROUND AND OBJECTIVES: Gingival and periodontal diseases are associated with
specific bacterial infections. The main aim of the study was to know whether the
periodontitis is associated with an increased risk for acute myocardial
infarction (AMI) and to know the distribution of Porphyromonas gingivalis in
patients with acute myocardial infarction associated with chronic periodontitis
and acute myocardial infarction Groups. MATERIALS AND METHODS: Out of 50
patients, 20 were diagnosed as acute myocardial infarction associated with
chronic periodontitis (Group I), twenty patients were suffering from AMI (Group
II) and 10 patients were healthy (control Group III). RESULTS AND CONCLUSION:
Periodontal pathogens were identified by phenotypic, enzymatic and hybridization
methods. The total bacterial load and the number of Porphyromonas gingivalis
pathogens were more in Group I when compared to Group II and Group III. Thus, the
present study confirmed an association between periodontitis and AMI.
PMID- 25848512
TI - Detection of virulence genes (bvfA, virB and ure) in Brucella melitensis isolated
from aborted fetuses of sheep and goats.
AB - BACKGROUND AND OBJECTIVES: Brucella, causative of brucellosis, has some potential
virulence factors involved in Brucella replication and its strategies to
circumvent the immune response. One of them is the virB gene that encodes the
type IV secretion system proteins (T4SS) involved in intracellular replication of
organism. Brucella virulence factor A (bvfA), and urease (ure) has also been
described as being implicated in survival, and virulence in the hosts. The aim of
this study was to investigate the B. melitensis virulence factor genes among
Brucella isolated from aborted fetuses of sheep and goats in Fars province,
southern Iran. MATERIALS AND METHODS: A total of 42 isolates of B. melitensis
isolated from aborted fetuses between 2005-2011 in Fars province of Iran was used
in this study. PCR assay was performed in order to detect the virB, bvfA, and ure
genes using specific primers. RESULTS AND CONCLUSIONS: The frequency of bvfA,
virB, and ure genes was 78.50%, 73.80%, and 88.09% among all isolates
respectively. The results of the present study showed that most Brucella isolates
from this region have virulence factors genes (virB, bvfA, ure) in their genome,
and most B. melitensis had ure genes that has been hypothesized to play a role in
the pathogenesis of disease.
PMID- 25848511
TI - Comparison of five diagnostic methods for Helicobacter pylori.
AB - BACKGROUND AND OBJECTIVES: Invasive and non-invasive techniques are used to
diagnose H. pylori infection. Some factors influence the choice of a diagnostic
test, such as the sensitivity and specificity of the tests, the clinical
circumstances and the cost-effectiveness of the testing strategy. The aim of this
study was to reveal the relationship between different H. pylori infection
diagnosis methods, and clarify the application scope of each diagnosis method.
MATERIALS AND METHODS: patients were included in the study, and specimens
including biopsies, blood and stool were taken. Biopsies were evaluated by
hematoxylin and eosin, and Giemsa staining. A sequence of 294 bp in the ureC
(glmM) gene was amplified. The rapid urease test (RUT) was performed using a non
commercial validated test. Stool samples were analyzed using a polyclonal ELISA
stool antigen test. A serological assay for IgG antibodies was performed by a
commercial Helicobacter pylori IgG ELISA kit. RESULTS: According to the
predefined criteria, a total of 46 (50.5%) patients tested were positive by at
least 2 of the 3 biopsy-based methods. The best sensitivity (95.6%) belonged to
histology and RUT. The sensitivities of other tests including PCR, serology and
stool antigen test were 93.5%, 91.3% and 73.9%, respectively. RUT showed the best
specificity (100%), and the specificities of the other tests, including PCR,
stool antigen test, histology and serology, were 95.6%, 86.7%, 77.8% and 55.6%,
respectively. CONCLUSION: In view of the better results obtained for invasive vs
non-invasive tests, for a more accurate diagnosis, it is advisable not to solely
rely on non-invasive methods of H. Pylori diagnosis.
PMID- 25848513
TI - Comparison of histopathological analysis, culture and polymerase chain reaction
assays to detect mucormycosis in biopsy and blood specimens.
AB - BACKGROUND AND OBJECTIVES: The aim of this study was to compare direct
microscopic examination with culture and PCR for the diagnosis of Mucorales
infection in blood and tissue specimens. MATERIAL AND METHODS: Blood samples and
tissue specimens were obtained from 28 patients (total 58 samples) with suspected
invasive fungal infection and cultured on proper media. Direct smear of tissue
samples was done with potassium hydroxide, hematoxylin and eosin, and methenamine
silver staining. DNA extracted from blood and tissue specimens were used for semi
nested PCR targeting 18S rDNA of Mucorales species. RESULTS: Mucormycosis was
documented in 7/28 (25%) of tissue specimens with positive findings by direct
smear, of which PCR and culture were positive in 6 (86%) and 5 (70%) specimens,
respectively. The etiologic agents were Mucor spp. and Rhizopus spp. However,
culture and PCR results for all blood specimens were negative. CONCLUSIONS: As
the orders of Mucorales do not have well growth in culture media, PCR with tissue
specimens is more sensitive than tissue or blood culture methods. Unfortunately,
there is no alternative method for direct smear, which is an invasive method.
Molecular methods may be helpful in these cases.
PMID- 25848515
TI - The effect of ajowan (Carum copticum L.) essential oils on eukaryotic ruminal
microorganisms of Mehraban sheep.
AB - BACKGROUND AND OBJECTIVES: Essential oils may improve the utilization of
nutrients by ruminal microorganisms. The aim of this study was to assess the
effect of different doses of ajowan essential oils (AEO) on growth and fibrolytic
activity of anaerobic fungi, and generic distribution of ciliated protozoa (in
vitro). MATERIAL AND METHODS: Different doses of AEO (0, 150, 300, 450 and 600
ppm) were added to experimental tubes. The effect of AEO was evaluated on growth
and fibrolytic enzyme activity of an anaerobic fungus (Neocalimastix spp.).
Generic distribution of ciliated protozoa were evaluated in response to different
doses of AEO. RESULTS AND CONCLUSION: The growth of fungus (Neocalimastix spp.)
were inhibited and activity of fibrolytic enzymes of fungus were reduced by
adding AEO. Also, an inhibitory effect was seen in concentration of ciliated
protozoa and some genus were completely disappeared at the doses of 300 ppm and
higher. The doses used in this study reduced the fibrolytic activity of the
studied rumen microorganisms which is undesirable in practical animal nutrition.
Further research is needed to assess the effects of AEO at lower doses on these
parameters and also proteolysis and methanogenesis.
PMID- 25848514
TI - Colonization of Pneumocystis jirovecii in Chronic Obstructive Pulmonary Disease
(COPD) patients and the rate of Pneumocystis pneumonia in Iranian non-HIV(+)
immunocompromised patients.
AB - BACKGROUND AND OBJECTIVES: With increasing rate of immunodeficiency diseases in
the world, opportunistic micro-organism such as Pneumocystis jirovecii (P.
jirovecii) become more important. Little information is available on prevalence
of this life-threatening microorganism in Iran. This study was designed to
determine the colonization and the rate of active disease caused by P. jirovecii
in two groups of Iranian immunosuppressed patients. MATERIALS AND METHODS: Two
hundred and fifty five pulmonary samples were collected from two groups of
immunosuppressed patients to detect a 260bp fragment of mt LSU rRNA gene of P.
jirovecii by nested PCR. The first group was COPD patients consumed oral, inhaled
or injectable corticosteroid and the second group was patients with malignancies
under chemotherapy. Both groups were referred to National Research Institute of
Tuberculosis and Lung Disease and Imam Khomeini hospital because of pulmonary
symptoms. All patients introduced to this project were confirmed HIV sera
negative by ELISA and western blot test. RESULTS: The mean age of COPD patients
was 66.5 +/- 11 (41-88) years and all of them were men. The mean age of patients
with malignancy (PMs) was 43 +/- 11 (23-65) years and 51.6% were men. The P.
jirovecii was colonized in 7 of 89 COPD patients (7.9%) and its DNA was isolated
from 11 of 153 PMs (7.2%). The microorganism could cause active disease in 7 of
67 (10.5%) PMs who suffered from pneumonia. CONCLUSION: The study showed that P.
jirovecii was one of colonizing agents in the COPD patients, but it could cause
active disease in PMs. Generally, the microorganism can exist in the lung of non
HIV(+) immunosuppressed patients. Therefore, it should be considered as a
potential infective agent in non-HIV(+) immunocompromised patients.
PMID- 25848516
TI - Characterization of a lipase from a newly isolated Pseudomonas sp.
AB - BACKGROUND AND OBJECTIVES: Lipases are valuable biocatalysts which are widely
used in the detergent, food, dairy and pharmaceutical industries. The aims of the
present study included the isolation of a lipase-producer from industrial zones
and the partial characterization of the enzyme. MATERIALS AND METHODS: A number
of bacteria were isolated from sites related to the oil industries. An isolate
forming a halo zone in a selective medium (TW agar) was then selected and grown
on a medium suitable for the production of lipase. The isolate was subsequently
identified by the 16S rRNA sequencing method, and its enzyme activity was
measured by a spectrophotometer using pNPP as a substrate. RESULTS: The selected
isolate was identified by the molecular method as Pseudomonas sp. Its
extracellular lipase activity was 41.5 +/- 1.4 U/ml, and the high affinity of
this enzyme for the substrate was indicated by the kinetic parameters of Km and
Vm, which were estimated by the the Lineweaver-Burk plot as 0.77 mM and 49.5
U/ml, respectively. Activation energy of lipase calculated from the Arrhenius
plot was found to be 20.78 kJ/mol, and a temperature coefficient (Q10) of 4.39
indicated the high catalytic activity of the enzyme and the temperature
dependence of the enzymatic reaction. CONCLUSION: The results demonstrated that
the indigenous isolate could have potential applications in many relevant
industries.
PMID- 25848517
TI - Inhibition of aflatoxin biosynthesis in Aspergillus flavus by phenolic compounds
extracted of Piper betle L.
AB - BACKGROUND AND OBJECTIVES: Food contamination by aflatoxins is an important food
safety concern for agricultural products. In order to identify and develop novel
antifungal agents, several plant extracts and isolated compounds have been
evaluated for their bioactivities. Anti-infectious activity of Piper betle used
in traditional medicine of Malaysia has been reported previously. MATERIALS AND
METHODS: Crude methanol extract from P. betel powdered leaves was partitioned
between chloroform and water. The fractions were tested against A. flavus UPMC
89, a strong aflatoxin producing strain. Inhibition of mycelial growth and
aflatoxin biosynthesis were tested by disk diffusion and macrodillution
techniques, respectively. The presence of aflatoxin was determined by thin-layer
chromatography (TLC) and fluorescence spectroscopy techniques using AFB1
standard. The chloroform soluble compounds were identified using HPLC-Tandem mass
spectrometry technique. RESULTS: The results, evaluated by measuring the mycelial
growth and quantification of aflatoxin B1(AFLB1) production in broth medium
revealed that chloroform soluble compounds extract from P. betle dried leaves was
able to block the aflatoxin biosynthesis pathway at concentration of 500MUg/ml
without a significant effect on mycelium growth. In analyzing of this effective
fractions using HPLC-MS(2) with ESI ionization technique, 11 phenolic compounds
were identified. CONCLUSION: The results showed that the certain phenolic
compounds are able to decline the aflatoxin production in A. flavus with no
significant effect on the fungus mycelia growth. The result also suggested P.
betle could be used as potential antitoxin product.
PMID- 25848518
TI - Screening, identification and optimization of a yeast strain, Candida
palmioleophila JKS4, capable of azo dye decolorization.
AB - BACKGROUND AND OBJECTIVES: Synthetic dyes are recalcitrant to degradation and
toxic to different organisms. Decolorization of textile wastewaters is one of the
major concerns since last decades. Physical-chemical treatments are very
expensive and frequently producing large amounts of toxic wastes. Biological
treatments can be more convenient. In the present study, an attempt has been made
for decolorization of azo dyes using microbial process. MATERIAL AND METHODS:
Screening of microorganisms capable of azo dye decolorization was performed from
activated sludge. The decolorization of various dyes (Reactive Black 5, Reactive
Orange 16, Reactive Red 198, Direct Blue 71, Direct Yellow 12 and Direct Black
22) was determined by measuring the absorbance of culture supernatant at their
lambdamax. Culture supernatants were also analyzed for UV-Vis absorption between
200-800 nm. The effect of aeration, temperature, different concentrations of
glucose and NaCl was studied with an aim to determine the optimal conditions
required for maximum decolorization. RESULTS: The yeast (strain JKS4) which had
high ability to decolorize different azo dyes was isolated. Under aerobic
condition, the yeast strain showed 85.7% of decolorization at 200 mg/l Reactive
Black 5 (as a model azo dye), 1% (w/v) glucose concentration and 35 degrees C
after 24 h. All the examined dyes were extensively decolorized (53.35-97.9%)
after 24 h. With elongated incubation period, complete decolorization was
observed in presence of all dyes. From the physiological properties and
phylogenetic analysis based on the 26S rDNA sequences, strain JKS4 was classified
into Candida palmioleophila. CONCLUSIONS: Because of high decolorizing activity
against various azo dyes commonly used in the textile industries, it is proposed
that the isolated yeast may have a practical application in the biotransformation
of various dye effluents.
PMID- 25848519
TI - Detection of AmpC-beta-lactamases producing isolates among carbapenem resistant
P. aeruginosa isolated from burn patient.
AB - BACKGROUND AND OBJECTIVES: Pseudomonas aeruginosa is responsible for devastating
nosocomial infections among severely burn patients. Class C of cephalosporinase
(AmpC-beta-lactamases) is important cause of multiple beta-lactam resistance in
P. aeruginosa. The aim of this study was to detect the AmpC-beta-lactamases
producing isolates among carbapenem resistant P. aeruginosa isolated from burn
patient. MATERIAL AND METHODS: a total of 100 isolates of carbapenem resistant P.
aeruginosa isolates from different burn patients were investigated. Three
phenotypic methods were selected for identification of the AmpC-beta-lactamases
producing isolates. RESULTS: Fifty four isolates were AmpC producer as detected
by AmpC disk test. Seventeen isolates were identified as AmpC producer using
combined disk method. Fifty two isolates showed a twofold or threefold dilution
difference between the minimum inhibitory concentration of imipenem or
ceftazidime and the minimum inhibitory concentration of imipenem or ceftazidime
plus cloxacillin. One isolate was identified as AmpC producer using three
methods. Three isolates produced AmpC as detected by both AmpC disk test and
combined disk methods and 19 isolates were found as AmpC producer using both AmpC
disk test and minimum inhibitory concentration methods. Six isolates were AmpC
producer as shown by the MICs of both imipenem and ceftazidime. CONCLUSION:
According to the results of this study, AmpC- beta-lactamase looks to be the main
mechanism of resistance of Pseudomonas aeruginosa to cephalosporins and
carbapenems in the study hospital.
PMID- 25848520
TI - Prevalence assessment of magA gene and antimicrobial susceptibility of Klebsiella
pneumoniae isolated from clinical specimens in Shahrekord, Iran.
AB - BACKGROUND AND OBJECTIVES: Klebsiella pneumoniae (K. pneumoniae) is an
opportunistic microorganism. This study aimed to investigate the presence of magA
gene and antimicrobial susceptibility in K. pneumoniae. MATERIALS AND METHODS:
clinical specimens were collected from hospitals of Shahrekord, Iran. Bacterial
culture, biochemical diagnostic standard test, determination of antibiotic
sensitivity, phenotypic testing hypermucoviscosity (HV) and polymerase chain
reaction (PCR) was performed for isolation and characterization of K. pneumoniae.
RESULTS: 173 samples were positive for K. pneumoniae. The highest and lowest
rates of resistance were related to amoxicillin 79.19% and ciprofloxacin 15.60%,
respectively. Also 4 samples were positive for magA gene. CONCLUSION: Based on
our results, K. pneumoniae strains were resistant to different antibiotics.
Knowing how to identify strains of K. pneumoniae, spreading of its virulence and
also antimicrobial resistance genes can be useful in treatment of infection
caused by this bacterium.
PMID- 25848521
TI - Immunogenicity comparison of conjugate vaccines composed of alginate and
lipopolysaccharide of Pseudomonas aeruginosa bound to diphtheria toxoid.
AB - BACKGROUND AND OBJECTIVES: Treatment of Pseudomonas aeruginosa infections is
greatly hampered by innate and acquired antibiotic resistance. The goal of this
study was to compure the immunogenicity of conjugates of P. aeruginosa
depolymerized alginate-diphtheria toxoid (D-ALGDT) and P. aeruginosa detoxified
lipopolysaccharidediphtheria toxoid (D-LPSDT) in mouse model. MATERIALS AND
METHODS: Alginate and LPS were purified from P. aeruginosa strain PAO1. The
resulting depolymerized alginate (D-ALG) and detoxified LPS (D-LPS) were
covalently coupled to diphtheria toxoid (DT) as a carrier protein with adipic
acid dihydrazide (ADH) as a spacer molecule and carbodiimide as a linker.
Sterility, safety and pyrogenicity tests were performed. 30 mice in two groups
were immunized intraperitoneally on days 0, 14 and 28 with 10 MUg of D-ALGDT and
D-LPSDT. Conjugates specific antibody levels were also determined by enzyme
linked immunosorbent assay (ELISA). RESULTS: The conjugates were non-toxic and
non-pyrogenic. Conjugates of D-ALGDT and D-LPSDT were shown to be safe and to
elicit total IgG, IgM, IgA, IgG1, IgG2a, IgG2b and IgG3 antibodies in mice. ELISA
results indicated that antibodies titer of D-ALGDT was more than D-LPSDT.
CONCLUSION: Immunization with D-ALGDT showed significant increase in all types of
antibodies titers in versus D-LPSDT, suggesting D-ALGDT as a vaccine candidate
against P. aeruginosa infections.
PMID- 25848522
TI - Immunological detection of 34 KDa outer membrane protein as a functional form of
OipA in clinical isolates of Helicobacter pylori.
AB - BACKGROUND AND OBJECTIVE: An outer membrane protein (OMP) of Helicobacter pylori
namely OipA, is an important virulence factor associated with peptic ulcer and
gastric cancer risks. The purpose of this study was to isolate the 34 KDa OMP of
H. pylori and evaluate its immunogenicity in experimental animals for rapid
detection of more virulent H. pylori isolates. MATERIAL AND METHODS: Sarcosine
insoluble fraction of membrane proteins (OMPs) were prepared from 15 clinical
isolates of H. pylori and their profiles were analyzed by SDS-PAGE. Two out of 15
isolates which demonstrated higher expression for apparent 34 KDa proteins were
selected. Under optimal conditions, 34 KDa protein was recovered from 5% SDS
Agarose gel, purified and injected into the New Zealand white rabbits with
Fruend's adjuvant in multiple stages with two weeks intervals. Collected
antiserum was purified through affinity chromatography with Sepharose column and
its titer was determined by ELISA. Specific immune response was demonstrated by
Dot blot and western blotting methods. RESULTS: The titer of antibody was
determined about 1/3000 and western blotting demonstrated a 34 KD-protein.
Screening of various strains by Dot blot method for its presence showed that its
expression was more frequent in strains isolated from the patients with more
severe pathology. CONCLUSION: High titer obtained for pAbs antibody, suggested
the high immunogenicity of this protein in experimental animals. Detection of 34
KDa OMP in strains isolated from the patients with more severe pathology proposes
the possible application of this pAbs in detecting more virulent strains of H.
pylori.
PMID- 25848523
TI - Application of Deletion- Targeted Multiplex PCR technique for detection of
Mycobacterium tuberculosis Beijing strains in samples from tuberculosis patients.
AB - BACKGROUND AND OBJECTIVE: Molecular epidemiological studies have shown that
certain genotypes of Mycobacterium tuberculosis (MTB) are over-represented in
limited geographical regions, suggesting of evolution of certain genotypes with
increasing virulence and pathogenicity. Beijing strain of MTB was initially
described by its potential to cause outbreaks worldwide and its association with
drug resistance. Due to tuberculosis (TB)-related mortality which is associated
with Beijing genotype, this study was designed with the aim to detect the MTB
Beijing genotype in the region of study. MATERIALS AND METHODS: A total of 170
clinical isolates of MTB were collected from the TB reference laboratory of
Khuzestan province, Iran, over one year period from February 2010 to February
2011. Phenotypic tests were used for preliminary detection of MTB. Culture
positive MTB isolates were confirmed by multiplex PCR based on IS6110 gene with
subsequent screening for resistance to isoniazid (INH), and rifampin (RIF) by PCR
using relevant primers. Three set of primers were used to differentiate Beijing
from non-Beijing strains by using Deletion- Targeted Multiplex (DTM) PCR.
RESULTS: From 160 PCR-confirmed MTB isolates, 18 (11.25%) showed mutation in katG
gene related to INH resistance and 20 (12.5%), associated with mutation in rpoB
gene related to RIF resistance, and 8 (5%) were detected as Beijing strain using
multiplex PCR. The majority of detected Beijing strains (6/8[75%]) comprised
mutation in katG gene with the prevalent mutation specifically in codon 315. In 4
Beijing strains (2.5%), mutation in rpoB gene were also detected. CONCLUSION:
Using DTM- PCR, the rate of Beijing strains in the region of study was determined
as 5%. Although for detection of MTB antimicrobial resistance, it is advised to
use a combination of conventional antimicrobial susceptibility testing and
molecular techniques, however for time saving, it seems that DTM-PCR, is a simple
technique for use in areas of the world where Beijing strains are highly
prevalent.
PMID- 25848524
TI - Development and evaluation of a Quadruplex Taq Man real-time PCR assay for
simultaneous detection of clinical isolates of Enterococcus faecalis,
Enterococcus faecium and their vanA and vanB genotypes.
AB - BACKGROUND AND OBJECTIVES: We developed and evaluated the utility of a quadruplex
Taqman real-time PCR assay that allows simultaneous identification of vancomycin
resistant genotypes and clinically relevant enterococci. MATERIALS AND METHODS:
The specificity of the assay was tested using reference strains of vancomycin
resistant and susceptible enterococci. In total, 193 clinical isolates were
identified and subsequently genotyped using a Quadruplex Taqman real-time PCR
assay and melting curve analysis. Representative Quadruplex Taqman real-time PCR
amplification curve were obtained for Enterococcus faecium, Enterococcus
faecalis, vanA-containing E. faecium, vanB-containing E. faecalis. RESULTS:
Phenotypic and genotypic analysis of the isolates gave same results for 82
enterococcal isolates, while in 5 isolates, they were inconsistent. We had three
mixed strains, which were detected by the TaqMan real-time PCR assay and could
not be identified correctly using phenotypic methods. CONCLUSION: Vancomycin
resistant enterococci (VRE) genotyping and identification of clinically relevant
enterococci were rapidly and correctly performed using TaqMan real-time multiplex
real-time PCR assay.
PMID- 25848525
TI - Comparison of four diagnostic methods for detection of methicillin resistant
Staphylococcus aureus.
AB - BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is
a well-known pathogen with a worldwide distribution. Given the increasing rate of
MRSA infections, implementing of reliable, accurate and rapid testing for
diagnosis of MRSA is necessary. The aim of this study was to compare four
diagnostic methods for detection of MRSA isolates. MATERIALS AND METHODS: From
December 2012 to April 2014, 120 S. aureus isolates were collected from three
hospitals affiliated with Tehran University of Medical Sciences. MRSA isolates
were detected by four different methods including cefoxitin disc diffusion test,
oxacillin disc diffusion test, minimum inhibitory concentration (MIC) of
oxacillin as determined by MIC test strip, and mecA detection by PCR. RESULTS:
Out of 120 S. aureus isolates, cefoxitin disc diffusion test, oxacillin disc
diffusion test and MIC test strip identified 60 (50%), 48 (40%), 55 (45.83%)
isolates as MRSA, respectively. The sensitivity and specificity for oxacillin
disc diffusion, cefoxitin disc diffusion and MIC of oxacillin were 80% and 100%,
100% and 100%, and 91.6% and 100%, respectively. CONCLUSION: Cefoxitin disc
diffusion test is reliable substitute for detection of MRSA in clinical
laboratory where MIC detection and molecular methods are not accessible.
PMID- 25848526
TI - Prevalence of enterotoxigenic Staphylococcus aureus in organic milk and cheese in
Tabriz, Iran.
AB - BACKGROUND AND OBJECTIVES: Staphylococcal food poisoning is a gastrointestinal
disease, which is caused by consumption of contaminated food with enterotoxins
produced by Staphylococcus aureus (SEs). Milk and its products are known sources
of food borne diseases. This study was carried out to evaluate the prevalence of
enterotoxigenic S. aureus strains in organic milk and cheese in Tabriz - Iran.
MATERIALS AND METHODS: A total of 200 samples (100 milk samples and 100 cheese
samples) were collected from farms and milk collection points in Tabriz - Iran.
The samples were cultured and identified by standard bacteriological methods,
then PCR was performed to detect sea gene. RESULTS AND CONCLUSION: Staphylococcus
aureus was found in 27% of all samples (milk and cheese). Results of PCR showed
that 12.96% of S. aureus isolates possessed sea gene. It suggested the potential
public health threat of S. aureus resulting from contamination of dairy products.
So, efforts are required to improve safety standards for preventing
staphylococcal food poisoning.
PMID- 25848527
TI - No evidence for occult HBV infection in hepatitis B vaccine non-responders.
AB - BACKGROUND AND OBJECTIVE: Although hepatitis B vaccine immunogenicity is high,
certain risk factors such as age, tobacco consumption, obesity and genetic
background have been associated with low responsiveness to HBV vaccine. We aimed
to evaluate the role of occult hepatitis B virus (HBV) infection in non-responder
adults to HBV vaccine in a low endemic area for HBV. MATERIAL AND METHODS: A
total of 52 subjects who were non-responder to HBV vaccine were enrolled in the
study. HBsAg, anti-HBs and anti-HBc were tested in all subjects. The presence of
HBV-DNA was determined in plasma samples by real-time PCR. RESULTS: A total of 52
cases with median age 34 years were enrolled in the study. 63.5% of patients were
male and 36.5% were female. Isolated anti-HBc (HBsAg negative, anti-HBs negative
and anti-HBc positive) was detected in 3.8% of cases. HBV-DNA was not detected in
our cases. CONCLUSION: This study showed no evidence of occult HBV infection in
our HBV vaccine non-responders even in cases with isolated anti-HBc.
PMID- 25848528
TI - Clinical and epidemiological features of the genus Malassezia in Iran.
AB - BACKGROUND AND OBJECTIVES: The genus Malassezia contains an expanding list of
lipophilic yeasts involve in the etiology of various superficial fungal
infections. Pityriasis versicolor (PV) is the most prevalent Malassezia-related
infection distributed worldwide. In the present study, clinical and
epidemiological features of the genus Malassezia are discussed with special focus
on PV in Iran. MATERIALS AND METHODS: During June 2012 to April 2013, among 713
confirmed cases of fungal infections, 68 (9.5%) were diagnosed as PV by positive
direct microscopy results in 20% potassium hydroxide (KOH) preparation of skin
scrapings. All the specimens were cultured on modified Dixon agar and incubated
at 32 degrees C for 10 days. Identification of the isolated yeasts was carried
out based on macro- and microscopic morphology, catalase test, utilization of
Tweens, polyethoxylated castor oil (EL slant), and hydrolysis of esculin and
utilization of Tween-60 (TE slant). RESULTS: Out of 68 skin scrapings, 55 (80.9%)
yielded yeast colonies on mDixon's agar which were finally identified as M.
globosa (36.36%), M. pachydermatis (29.08%), M. furfur (23.65%), M. slooffiae
(7.28%) and M. obtusa (3.64%). CONCLUSION: Results of the present study further
indicate clinico-epidemiological importance of the genus Malassezia with growing
importance of M. pachydermatis as a major species involve in the etiology of
pityriasis versicolor. These findings are of major concern in management of
Malassezia-related diseases.
PMID- 25848529
TI - Isolation and molecular identification of deteriorating fungi from Cyrus the
Great tomb stones.
AB - BACKGROUND AND OBJECTIVES: Biodeterioration is an irreversible damage that is
caused by colonization of microorganisms on the surface of different materials.
Among all microorganisms, fungi play an important role in deterioration of
materials. Fungi can colonize on stone surfaces and by secreting different
enzymes, organic and inorganic acids and pigments, can cause bio-weathering and
changing not only the substrate materials but the color of stones. Furthermore,
fungal mycelia can penetrate into the internal surfaces of stones and change the
interior chemical contents of stones. Pasargadae including Cyrus the Great Tomb
is entitled by UNESCO as one of the World Heritage Sites. This study was focused
on the identification of fungi that were colonized on the tomb limestone
monument. MATERIALS AND METHODS: Sampling of stone was carried out to identify
inhabiting molds and yeasts. biochemical and microscopic methods were used for
isolated strains. In addition, the Polymerase Chain Reaction (PCR) and sequencing
of the PCR products were done. Finally, phylogenic tree was constructed basde on
the sequences of ITs region. RESULTS AND CONCLUSION: The common inhabiting fungi
which isolated from the tomb limestone belong to Caldosporium sp., Embellisia
sp., Cryptococcus sp., Candida sp., Meyerozyma sp., Arthirinium sp., Ulocladium
sp., Fusarium sp., Humicola sp. and Pseudozyma sp.. Stereomicroscopic and
Scanning Electron Microscope images and XRD, were taken from pieces of stone
samples and indicated the severe pattern damages such as pitting,
biomineralization, etching and sugaring on the surfaces of stones.
PMID- 25848530
TI - Development and validation of a classification approach for extracting severity
automatically from electronic health records.
AB - BACKGROUND: Electronic Health Records (EHRs) contain a wealth of information
useful for studying clinical phenotype-genotype relationships. Severity is
important for distinguishing among phenotypes; however other severity indices
classify patient-level severity (e.g., mild vs. acute dermatitis) rather than
phenotype-level severity (e.g., acne vs. myocardial infarction). Phenotype-level
severity is independent of the individual patient's state and is relative to
other phenotypes. Further, phenotype-level severity does not change based on the
individual patient. For example, acne is mild at the phenotype-level and relative
to other phenotypes. Therefore, a given patient may have a severe form of acne
(this is the patient-level severity), but this does not effect its overall
designation as a mild phenotype at the phenotype-level. METHODS: We present a
method for classifying severity at the phenotype-level that uses the Systemized
Nomenclature of Medicine - Clinical Terms. Our method is called the
Classification Approach for Extracting Severity Automatically from Electronic
Health Records (CAESAR). CAESAR combines multiple severity measures - number of
comorbidities, medications, procedures, cost, treatment time, and a proportional
index term. CAESAR employs a random forest algorithm and these severity measures
to discriminate between severe and mild phenotypes. RESULTS: Using a random
forest algorithm and these severity measures as input, CAESAR differentiates
between severe and mild phenotypes (sensitivity = 91.67, specificity = 77.78)
when compared to a manually evaluated reference standard (k = 0.716).
CONCLUSIONS: CAESAR enables researchers to measure phenotype severity from EHRs
to identify phenotypes that are important for comparative effectiveness research.
PMID- 25848531
TI - Pharmacological manipulation of transcription factor protein-protein
interactions: opportunities and obstacles.
AB - Much research on transcription factor biology and their genetic pathways has been
undertaken over the last 30 years, especially in the field of developmental
biology and cancer. Yet, very little is known about the molecular modalities of
highly dynamic interactions between transcription factors, genomic DNA, and
protein partners. Methodological breakthroughs such as RNA-seq (RNA-sequencing),
ChIP-seq (chromatin immunoprecipitation sequencing), RIME (rapid
immunoprecipitation mass spectrometry of endogenous proteins), and single
molecule imaging will dramatically accelerate the discovery rate of their
molecular mode of action in the next few years. From a pharmacological viewpoint,
conventional methods used to target transcription factor activity with molecules
mimicking endogenous ligands fail to achieve high specificity and are limited by
a lack of identification of new molecular targets. Protein-protein interactions
are likely to represent one of the next major classes of therapeutic targets.
Transcription factors, known to act mostly via protein-protein interaction, may
well be at the forefront of this type of drug development. One hurdle in this
field remains the difficulty to collate structural data into meaningful
information for rational drug design. Another hurdle is the lack of chemical
libraries meeting the structural requirements of protein-protein interaction
disruption. As more attempts at modulating transcription factor activity are
undertaken, valuable knowledge will be accumulated on the modality of action
required to modulate transcription and how these findings can be applied to
developing transcription factor drugs. Key discoveries will spawn into new
therapeutic approaches not only as anticancer targets but also for other
indications, such as those with an inflammatory component including
neurodegenerative disorders, diabetes, and chronic liver and kidney diseases.
PMID- 25848533
TI - Bone microdamage, remodeling and bone fragility: how much damage is too much
damage?
AB - Microdamage resulting from fatigue or 'wear and tear' loading contributes to bone
fragility; however, the full extent of its influence is not completely
understood. Linear microcracks (~50-100 MUm) and diffuse damage (clusters of
sublamellar-sized cracks) are the two major bone microdamage types, each with
different mechanical and biological consequences. Healthy bone, due to its
numerous microstructural interfaces and its ability to affect matrix level
repair, deals effectively with microdamage. From a material standpoint, healthy
bone behaves much like engineering composites like carbon-fiber reinforced
plastics. Both materials allow matrix damage to form during fatigue loading and
use microstructural interfaces to dissipate energy and limit microcrack
propagation to slow fracture. The terms fracture toughness and 'toughening
mechanism', respectively, describe mechanical behavior and microstructural
features that prevent crack growth and make it harder to fracture a material.
Critically, toughness is independent of strength. In bone, primary toughening
features include mineral and collagen interfaces, lamellae and tissue
heterogeneity among osteons. The damage tolerance of bone and other composites
can be overcome with sustained loading and/or matrix changes such that the
microstructure no longer limits microcrack propagation. With reduced remodeling
due to aging, disease or remodeling suppression, microdamage accumulation can
occur along with loss of tissue heterogeneity. Both contribute additively to
reduced fracture toughness. Thus, the answer to the key question for bone
fragility of how much microdamage is too much is extremely complex. It ultimately
depends on the interplay between matrix damage content, internal repair and
effectiveness of matrix-toughening mechanisms.
PMID- 25848532
TI - Molecular alterations that drive breast cancer metastasis to bone.
AB - Epithelial cancers including breast and prostate commonly progress to form
incurable bone metastases. For this to occur, cancer cells must adapt their
phenotype and behaviour to enable detachment from the primary tumour, invasion
into the vasculature, and homing to and subsequent colonisation of bone. It is
widely accepted that the metastatic process is driven by the transformation of
cancer cells from a sessile epithelial to a motile mesenchymal phenotype through
epithelial-mesenchymal transition (EMT). Dissemination of these motile cells into
the circulation provides the conduit for cells to metastasise to distant organs.
However, accumulating evidence suggests that EMT is not sufficient for metastasis
to occur and that specific tissue-homing factors are required for tumour cells to
lodge and grow in bone. Once tumour cells are disseminated in the bone
environment, they can revert into an epithelial phenotype through the reverse
process of mesenchymal-epithelial transition (MET) and form secondary tumours. In
this review, we describe the molecular alterations undertaken by breast cancer
cells at each stage of the metastatic cascade and discuss how these changes
facilitate bone metastasis.
PMID- 25848534
TI - Role of syndecan-2 in osteoblast biology and pathology.
AB - Syndecans 1-4 are a family of transmembrane proteins composed of a core protein
and glycosaminoglycan chains. Although the four syndecans have common functions,
they appear to be connected to different signaling pathways, and their expression
occurs in a cell- and development-specific pattern. In contrast to other
syndecans, syndecan-2 expression increases during osteoblast differentiation.
Mechanistically, syndecan-2 exerts multiple functions in cells of the osteoblast
lineage as it serves as a co-receptor for fibroblast growth factors and Wnt
proteins and controls cell adhesion, proliferation, differentiation and
apoptosis. Recent studies indicate that syndecan-2 also contributes to
osteosarcoma cell response to cytotoxic agents through interactions with Wnt/beta
catenin signaling. Here we summarize our current understanding of the role of
syndecan-2 in the control of osteoblast biology and pathology and discuss how
syndecan-2 acts as a modulator of the bone cell microenvironment.
PMID- 25848536
TI - Assessment of the therapeutic value of new medicines marketed in Australia.
PMID- 25848535
TI - Metabolite profiling in posttraumatic stress disorder.
AB - BACKGROUND: Traumatic stress does not only increase the risk for posttraumatic
stress disorder (PTSD), but is also associated with adverse secondary physical
health outcomes. Despite increasing efforts, we only begin to understand the
underlying biomolecular processes. The hypothesis-free assessment of a wide range
of metabolites (termed metabolite profiling) might contribute to the discovery of
biological pathways underlying PTSD. METHODS: Here, we present the results of the
first metabolite profiling study in PTSD, which investigated peripheral blood
serum samples of 20 PTSD patients and 18 controls. We performed liquid
chromatography (LC) coupled to Quadrupole/Time-Of-Flight (QTOF) mass
spectrometry. Two complementary statistical approaches were used to identify
metabolites associated with PTSD status including univariate analyses and Partial
Least Squares Discriminant Analysis (PLS-DA). RESULTS: Thirteen metabolites
displayed significant changes in PTSD, including four glycerophospholipids, and
one metabolite involved in endocannabinoid signaling. A biomarker panel of 19
metabolites classifies PTSD with 85% accuracy, while classification accuracy from
the glycerophospholipid with the highest differentiating ability already reached
82%. CONCLUSIONS: This study illustrates the feasibility and utility of
metabolite profiling for PTSD and suggests lipid-derived and endocannabinoid
signaling as potential biological pathways involved in trauma-associated
pathophysiology.
PMID- 25848537
TI - Response to Michael Wonder's comments on the article 'Assessment of the
therapeutic value of new medicines marketed in Australia'.
PMID- 25848538
TI - Antibiotic prescribing in women during and after delivery in a non-teaching,
tertiary care hospital in Ujjain, India: a prospective cross-sectional study.
AB - OBJECTIVES: Antibacterial drugs (hereafter referred to as antibiotics) are
crucial to treat infections during delivery and postpartum period to reduce
maternal mortality. Institutional deliveries have the potential to save lives of
many women but extensive use of antibiotics, add to the development and spread of
antibiotic resistance. The aim of this study was to present antibiotic
prescribing among inpatients during and after delivery in a non-teaching,
tertiary care hospital in the city of Ujjain, Madhya Pradesh, India. METHODS: A
prospective cross-sectional study was conducted including women having had either
a vaginal delivery or a cesarean section in the hospital. Trained nursing staff
collected the data on daily bases, using a specific form attached to each patient
file. Statistical analysis, including bivariate and multivariable logistic
regression was conducted. RESULTS: Of the total 1077 women, 566 (53%) had a
vaginal delivery and 511 (47%) had a cesarean section. Eighty-seven percent of
the women that had a vaginal delivery and 98% of the women having a cesarean
section were prescribed antibiotics. The mean number of days on antibiotics in
hospital for the women with a vaginal delivery was 3.1 (+/-1.7) and for the women
with cesarean section was 6.0 (+/-2.5). Twenty-eight percent of both the women
with vaginal deliveries and the women with cesarean sections were prescribed
antibiotics at discharge. The most commonly prescribed antibiotic group in the
hospital for both the women that had a vaginal delivery and the women that had a
cesarean section were third-generation cephalosporins (J01DD). The total number
of defined daily doses (DDD) per100 bed days for women that had a vaginal
delivery was 101, and 127 for women that had a cesarean section. CONCLUSIONS: The
high percentage of women having had a vaginal delivery that received antibiotics
and the deviation from recommendation for cesarean section in the hospital is a
cause of concern. Improved maternal health and rational use of antibiotics are
intertwined. Specific policy and guidelines on how to prescribe antibiotics
during delivery at health care facilities are needed. Additionally, monitoring
system of antibiotic prescribing and resistance needs to be developed and
implemented.
PMID- 25848539
TI - Malaria treatment policies and drug efficacy in Haiti from 1955-2012.
AB - OBJECTIVES: Chloroquine (CQ), after 67 years of use in Haiti, is still part of
the official treatment policy for malaria. Several countries around the world
have used CQ in the past due to its low incidence of adverse events, therapeutic
efficacy, and affordability, but were forced to switch treatment policy due to
the development of widespread CQ resistance. The purpose of this paper was to
compile literature on malaria treatment policies and antimalarial drug efficacy
in Haiti over 67-year period. METHODS: A systematic review of PubMed, Web of
Science, and the Armed Forces Pest Management Board, was conducted to find
pertinent documents on national malaria treatment policies and antimalarial drug
efficacy studies in Haiti between 1955 and 2012. A total of 329 citations and
abstracts were reviewed independently by two researchers, of which thirty three
met the final inclusion criteria of studies occurring in Haiti between 1955 and
2012 which specifically discuss malaria treatment policies and drug efficacy.
RESULTS: Results suggest that CQ has been the predominant antimalarial drug in
use from 1955 to 2012. In 2010 single dose primaquine (PQ) was added to the
national treatment policy, however it is not clear whether this new policy has
been put into practice. CONCLUSIONS: Although no widespread CQ resistance has
been reported, some studies have detected low levels of CQ resistance. Increased
surveillance and monitoring for CQ resistance should be implemented in Haiti.
PMID- 25848540
TI - Economics and industry do not mean ethical conduct in clinical trials.
AB - Clinical trials present an ethical dilemma for pharmaceutical companies. While
companies may want to undertake and report these trials in an ethical manner,
negative results can significantly affect product sales. There is accumulating
evidence that company-financed trials are biased in favor of the product that the
company makes. Ethical conduct in this article is defined as whether the trials
are conducted in the best interests of the participants and/or reported in the
best interests of patients. Nine examples of how clinical trials are violating
multiple articles in the Declaration of Helsinki are discussed using concrete
case reports from the literature. The recognition of ethical problems in company
run trials is not something new, but to date no meaningful action has been taken
to resolve this issue. What is necessary is to separate the financing of clinical
trials from their conduct.
PMID- 25848542
TI - A research agenda to promote affordable and quality assured medicines.
AB - Promoting generic medicines to increase access to essential medicines is relevant
to achieve the Millennium Development Goal (MDGs) and post 2015 goals. There are
several barriers to encouraging wider use of generic medicines in health systems,
e.g. the widely-held perception that low price equals low quality and
misalignment of provider and consumer incentives. Overcoming the complex barriers
and other challenges can be re-formulated as a 'generic medicine evidence-based
policy agenda': (1) What policy and strategies can increase consumer trust in the
quality of all medicines granted market authority including generic products? (2)
Are there differences in prices between branded and unbranded generics? (3) What
are synergies between policies that can enhance promoting of generic medicines
effectively? Evaluating the policies promoting generic medicines will be critical
to create evidence that countries can use to implement policies in their local
settings.
PMID- 25848541
TI - Immigrant background and medicine use for aches: national representative study of
adolescents.
AB - OBJECTIVES: The aims of the study were to examine the association between
immigrant background and medicine use for headache and stomach-ache among
adolescents, and whether symptoms of headache and stomach-ache could explain the
differences in medicine use. METHODS: We used data from the Danish contribution
to the WHO-affiliated international cross-sectional survey Health Behaviour in
School-aged Children (HBSC) in 2006. Among boys, a total of 4170 ethnic Danes,
244 descendants of immigrants, and 224 immigrants participated. Among girls, 4310
ethnic Danes, 264 descendants of immigrants, and 232 immigrants were included.
The associations between migrant background and medicine use for headache and
stomach-ache by means of multilevel multivariate logistic regression analyses
adjusted for age group, symptoms and the clustering effect of school and
stratified by sex due to interactions. RESULTS: Among boys, the risk of medicine
use for stomach-ache was higher for immigrants (odds ratio (OR), 1.54; 95%
confidence intervals (CI), 0.99-2.44)) and descendants (OR, 1.97 (1.33-2.94))
compared to ethnic Danes. Similar associations were found for use of medicine for
stomach-ache for immigrant girls (OR, 1.55 (1.12-2.15) and use of medicine for
headache among boys (immigrants (OR, 1.36 (1.02-1.97 and descendants (1.48 (1.12
1.97)). Symptoms of aches were all independently associated with medicine use.
After adjusting for these factors the association between immigrant background
and medicine use attenuated slightly. CONCLUSION: Among adolescents in Denmark,
the risk of medicine use for headache and stomach-ache was higher for immigrants
and descendants as compared to ethnic Danes, with the exception of medicine use
for headache among girls.
PMID- 25848543
TI - Stock-outs of antiretroviral drugs and coping strategies used to prevent changes
in treatment regimens in Kinondoni District, Tanzania: a cross-sectional study.
AB - OBJECTIVES: Since 2004, the government of Tanzania has been rolling out
antiretroviral treatment programs all over the country. However, the capacity of
the health system to cope with the rapid scale-up of these programs is a major
concern, and problems may result in drug stock-outs that force changes in
treatment regimens. This study aims to explore stock-outs of antiretroviral drugs
and further determine the coping strategies employed to prevent changes in
treatment regimens in HIV/AIDS care and treatment clinics in Kinondoni District,
Dar es Salaam, Tanzania. METHODS: A cross-sectional study was conducted in 20
HIV/AIDS care and treatment clinics. Interviews were conducted with the person in
charge and a member of the pharmacy staff from each clinic using a pre-tested
semi-structured interview guide. Verbal responses were transcribed, coded and
analysed by thematic approach. Quantitative data were analysed using Excel
spreadsheet (Microsoft Excel(r), Microsoft Corporation). RESULTS: The total
number of clients enrolled in the visited clinics was 32,147, of whom 20,831
(64.8%) had already been initiated onto antiretroviral therapies (ART). Stock-out
of antiretroviral drugs was reported in 16 out of the 20 clinics, causing 210
patients to change their ART regimens, during the 12 months preceding the survey.
Inefficient supply systems, quantification problems and short expiry duration
were cited as the main causes of stock-outs. The coping strategies utilised to
prevent changes in ART regimens were: shortening of the refill period, borrowing
and moving patients to other clinics. CONCLUSION: Changes in ART regimens due to
stock-outs of antiretroviral drugs occurred in a small but significant number of
patients. This increases the risk of the emergence of drug-resistant HIV strains.
Healthcare workers use various coping strategies to prevent changes in ART
regimens but, unfortunately, some of these strategies are likely to increase
patient-borne costs, which may discourage them from attending their routine
clinics, hence leading to unplanned treatment interruptions.
PMID- 25848544
TI - An in-depth analysis of pharmaceutical regulation in the Republic of Moldova.
AB - OBJECTIVE: Regulation of the pharmaceutical system is a crucial, yet often
neglected, component in ensuring access to safe and effective medicines. The aim
of this study was to provide an in-depth analysis of the existing pharmaceutical
regulation, including recent changes, in the Republic of Moldova. METHODS: Data
from field work conducted by the World Health Organization (WHO) together with a
review of policy documents and quantitative secondary data analysis was used to
achieve this aim. RESULTS: This analysis identified several ways in which
pharmaceutical regulation affects availability of quality medicines in the
Republic of Moldova. These include lack of full implementation bioequivalence
requirements for generics registration, incomplete implementation of good
manufacturing practices and no implementation of good distribution practices, use
of quality control instead of quality assurance as a method to ensure quality of
medicines, frequent change of power within the Medicines and Medical Devices
Agency (MMDA) leading to lack of long-term strategy and plans, conflict of
interest between the different functions of the MMDA, the lack of sufficient
funding for the MMDA to conduct its activities and to invest in continuous
training of its staff (particularly inspectors) and very weak post-marketing
control. Notably, several improvements have been recently introduced, including a
roadmap for change for the MMDA, the introduction of good manufacturing practices
and the drafting of a quality manual for the Agency. CONCLUSION: Based on these
findings the authors propose a set of priority actions to address existing gaps
and draw lessons learned from other countries.
PMID- 25848545
TI - The Papua New Guinea medical supply system - documenting opportunities and
challenges to meet the Millennium Development Goals.
AB - OBJECTIVES: Limited human resources are widely recognised as an impediment to
achieving the health-related Millennium Development Goals in Pacific Island
Countries, with the availability of medical supplies and suitably trained health
personnel crucial to ensuring a well-functioning medical supply chain. This paper
presents our findings as we seek to answer the research question 'What factors
influence the availability of medical supplies within the health facilities of
Papua New Guinea?' METHODS: We used a qualitative, triangulated strategy using
semi-structured interviews, workplace observation and semi-structured focus
groups. The parallel use of the interview tool and workplace observation tool
allowed identification of 'know-do' gaps between what the interviewee said they
did in their work practices, and the actual evidence of these practices. Focus
groups provided further opportunities for raising and elaborating issues.
RESULTS: During 2 weeks of data collection we conducted 17 interviews and 15
observational workplace surveys in 15 facilities. Sixteen health personnel
participated in 3 focus groups across 2 provinces and one district. An array of
medical supply issues across all levels of the medical supply chain were
revealed, including standard operating procedures, facilities, transport,
emergency medical kits, the cold chain and record keeping. The influence of
health worker training and competency was found to be common across all of these
issues. CONCLUSION: The factors influencing the availability of medical supplies
in PNG consist of a range of interrelating issues, consisting of both simple and
complex problems involving the different levels and cadres of workers within the
medical supply chain. Health systems sustainability theory suggests that a
coordinated approach which addresses the inter-related nature of these issues,
led by the PNG government and supported by suitable development partners, will be
required for sustainable health systems change to occur. These changes are
necessary for PNG to meet the health-related Millennium Development Goals.
PMID- 25848546
TI - Medicines discarded in household garbage: analysis of a pharmaceutical waste
sample in Vienna.
AB - OBJECTIVES: To analyze a sample of pharmaceutical waste drawn from household
garbage in Vienna, with the aim to learn whether and which medicines end up
unused in normal household waste. METHODS: We obtained a pharmaceutical waste
sample from the Vienna Municipal Waste Department. This was drawn by their staff
in a representative search in October and November 2009. We did a manual
investigation of the sample which contained packs and loose blisters, excluded
medical devices and traced loose blisters back to medicines packs. We reported
information on the prescription status, origin, therapeutic group, dose form,
contents and expiry date. We performed descriptive statistics for the total data
set and for sub-groups (e.g. items still containing some of original content).
RESULTS: In total, 152 packs were identified, of which the majority was
prescription-only medicines (74%). Cardiovascular medicines accounted for the
highest share (24%). 87% of the packs were in oral form. 95% of the packs had not
expired. 14.5% of the total data set contained contents but the range of content
left in the packs varied. Results on the packs with contents differed from the
total: the shares of Over-the Counter medicines (36%), of medicines of the
respiratory system (18%) and of the musculo-skeletal system (18%), for dermal use
(23%) and of expired medicines (19%) were higher compared to the full data set.
CONCLUSIONS: The study showed that some medicines end up unused or partially used
in normal household garbage in Vienna. Our results did not confirm speculations
about a high percentage of unused medicines improperly discarded. There is room
for improved patient information and counseling to enhance medication adherence
and a proper discharge of medicines.
PMID- 25848547
TI - Physicians' perception of generic and electronic prescribing: A descriptive study
from Jordan.
AB - OBJECTIVES: The aim of this study was to investigate Jordanian physicians'
perception and attitudes toward generic medicines and generic substitution. It
also aimed to examine factors that affect physicians' pattern of prescribing, and
to evaluate their opinion regarding future introduction of Electronic Prescribing
(EP) in Jordan. METHODS: A cross-sectional descriptive study involving Jordanian
physicians working in both public and private sectors was undertaken, using a
self-administrated anonymous questionnaire. Frequency tables, cross-tabulation
and chi square tests were used for data analysis. The response rate was 75.2% (n
= 376/500). RESULTS: Cost was claimed to be an important factor in the
prescribing decision for 69.1% of the Jordanian physicians. The majority of
physicians (77.4%) claimed that they often prescribe generic medicines. Jordanian
physicians predominantly welcomed the implementation of an EP and International
Nonproprietary Name (INN) prescribing systems with 92%, and 80.1% respectively.
More than two thirds of the physicians (69.4%) accepted generic substitution by
pharmacists, with a significant association with their employment sector;
physicians who work in the private sector tended to oppose generic substitution
compared with physicians who work in the public sector. Physicians mostly (72.1%)
opposed that generic substitution should only be allowed upon patient request.
CONCLUSIONS: Jordanian physicians have a positive attitude towards generic
medications and high willingness and acceptance of strategies that encourage
generic utilisation such as EP, INN prescribing and generic substitution. All
these strategies would help reduce the high expenditure on medicines in Jordan.
These findings would provide baseline data to policy makers to develop a robust
generic policy to achieve greater clinical effectiveness and economic efficiency
from medicines prescribing.
PMID- 25848548
TI - The future of medicines use and access research: using the Journal of
Pharmaceutical Policy and Practice as a platform for change.
PMID- 25848549
TI - Pharmaceutical Policy Part 2 Pharmaceutical engagement and policy development: a
framework for influence.
AB - The formulation of pharmaceutical policy is a critical component of healthcare
planning, made more important given that medicines are the ubiquitous technology
in the diagnosis, treatment and prevention of disease and constitute a
significant proportion of health care expenditure. Pharmacists need to inform
policy development that will, in its implementation, offer opportunity to deliver
greater rationality, safety, effectiveness and economy to the medicines use
process and where patients experience enhanced health outcomes. This is the
second of two articles directed to this specific issue focusing on how policy and
strategic change can be affected. This is discussed from three overlapping
perspectives - from the point of view of skills, that is, the skills or tactics
needed to be employed to effect change; secondly, from a structural standpoint in
terms of what positional arrangements exist that could be positively exploited;
and thirdly, the subject, particularly its relevance to the contemporary
situation. These approaches are then exemplified through a worked example on
medication safety and its application in practice.
PMID- 25848550
TI - MRI demyelination pattern and clinical course in a child with cerebral X-linked
adrenoleukodystrophy (X-ALD).
AB - The clinical spectrum in boys with X-linked adrenoleukodystrophy (X-ALD) ranges
from isolated adrenocortical insufficiency and slowly progressive myelopathy to
devastating cerebral demyelination. In the individual case, the disease course
still remains unpredictable. Research findings suggest an important role of brain
magnetic resonance imaging (MRI) lesion patterns as prognostic markers for X-ALD.
Hence, familiarity with imaging features of childhood X-ALD in combination with
clinical manifestation is required in order to stratify affected patients for
therapy. We report on MRI findings and clinical course of cerebral X-ALD in a
young boy with a rare subtype of white matter demyelination.
PMID- 25848551
TI - Role of duration of catheterization and length of hospital stay on the rate of
catheter-related hospital-acquired urinary tract infections.
AB - OBJECTIVE: Our aim is to prove that duration of catheterization and length of
hospital stay (LOS) are associated with the rate of hospital-acquired urinary
tract infections (UTI), while taking into account type of urinary catheter used,
the most common organisms found, patient diagnosis on admission, associated
comorbidities, age, sex, precautions that should be taken to avoid UTI, and
comparison with other studies. METHODS: The study was done in a university
teaching hospital with a 920-bed capacity; this hospital is a tertiary care
center in Riyadh, Saudi Arabia. The study was done on 250 selected patients
during the year 2010 as a retrospective descriptive study. Patients were selected
as purposive sample, all of them having been exposed to urinary catheterization;
hospital-acquired UTI were found in 100 patients. Data were abstracted from the
archived patients' files in the medical record department using the annual
infection control logbook prepared by the infection control department. The data
collected were demographic information about the patients, clinical condition
(diagnosis and the LOS), and possible risk factors for infection such as duration
of catheterization, exposure to invasive devices or surgical procedures, and
medical condition. RESULTS: There was a statistically significant association
between the rate of UTI and duration of catheterization: seven patients had UTI
out of 46 catheterized patients (15%) at 3 days of catheterization, while 30
patients had UTI out of 44 catheterized patients (68%) at 8 days of
catheterization (median 8 days in infected patients versus 3 days in noninfected
patients; P-value <0.05), which means that the longer the duration of
catheterization, the higher the UTI rate. There was a statistically significant
association between the rate of UTI and LOS: three patients had UTI out of 37
catheterized patients (8%) at 10 days LOS, while 42 patients had UTI out of 49
catheterized patients (85.7%) at 18 days LOS. The longer the LOS, the higher the
UTI rate: LOS for each patient (median 18 days for infected patients versus 10
days for noninfected patients; P-value <0.05), and number of hospital-acquired
catheter-related UTI (100 patients had UTI out of 250 catheterized patients,
P=0.04). CONCLUSION: Reduction of the duration of catheterization and LOS of the
patient have a positive impact in reduction of catheter-related UTI.
PMID- 25848552
TI - Exercise rehabilitation in era of convergence.
PMID- 25848553
TI - eGEMs: Pragmatic Publishing to Build a Learning Health System.
AB - The Electronic Data Methods (EDM) Forum announces the launch of eGEMs (Generating
Evidence and Methods to improve patient outcomes), a new, free, open access, peer
reviewed e-publication. eGEMs aims to disseminate innovative ideas about how
electronic clinical data (ECD) can be leveraged in comparative effectiveness
research (CER), patient-centered outcomes research (PCOR) and quality improvement
(QI). eGEMs seeks submissions in four main topic areas: analytic methods,
clinical informatics, governance, and the learning health system. The goal of
eGEMs is ultimately to promote dialogue and the sharing of ideas between
researchers and other stakeholders in a credible and timely way, extending the
efforts of the EDM Forum.
PMID- 25848554
TI - Learning How to Learn: How AcademyHealth is Supporting Evidence Generation in a
Transforming World.
AB - The field of health services research faces significant challenges as it aims to
address pressing issues of quality and cost in the US healthcare system. Major
advances in the availability of electronic clinical data (ECD) provide the
opportunity to address questions that are important to the recipients, providers,
and purchasers of health care. This is where eGEMs has a role to play, meeting an
expressed need in the scientific community by disseminating approaches and
methods for using ECD. eGEMs can help researchers address these important
questions and consider strategies to further improve the US healthcare system.
PMID- 25848555
TI - In Search of a Data-in-Once, Electronic Health Record-Linked, Multicenter
Registry-How Far We Have Come and How Far We Still Have to Go.
AB - The learning health system is a framework in which new knowledge is translated
into general clinical practice and clinical practice serves as the engine to
generate new evidence and knowledge. One type of learning health system is an
electronic health record (EHR)-linked multicenter registry. Significant
investment has been made in recent years to spur the adoption of EHRs and to fund
the creation of health information exchanges. Yet, given this investment, are we
any closer to achieving the vision of a learning health system? What are the
areas of success? What challenges remain? To answer these questions and using an
EHR-linked multicenter registry as a model, we define a set of requirements that
need to be met in order to achieve the goals of the learning health system. We
then evaluate progress along each dimension by detailing our efforts to create an
EHR-linked multicenter registry for ImproveCareNow, a quality improvement and
research network focused on improving outcomes for children with inflammatory
bowel disease (IBD).
PMID- 25848556
TI - Effect identification in comparative effectiveness research.
AB - The widespread adoption of electronic medical records means there are now vast
data resources available for comparative effectiveness research (CER). In concert
with conventional randomized controlled trials, CER holds great promise for
advancing our understanding of how different therapeutic treatments yield
different health outcomes in different settings and with different populations.
But in a research culture fixated on estimating correlations and p-values, the
threat of misinterpretation of results and improper CER inferences is troubling.
Accordingly, this paper aims to shore up the inferential foundations of CER by
introducing the fundamentals of effect identification, which is the process of
identifying or teasing out empirically defensible causal effects from competing
explanations. Three primary requirements of effect identification-positivity,
exchangeability, and consistency- are explained and simple exampled are given.
The take home message is that so-called big data from medical records may not
yield better or more useful results. Advances will come only when the right
question is addressed with the appropriate data and methods.
PMID- 25848557
TI - Ensuring Support for Research and Quality Improvement (QI) Networks: Four Pillars
of Sustainability-An Emerging Framework.
AB - Multi-institutional research and quality improvement (QI) projects using
electronic clinical data (ECD) hold great promise for improving quality of care
and patient outcomes but typically require significant infrastructure investments
both to initiate and maintain the project over its duration. Consequently, it is
important for these projects to think holistically about sustainability to ensure
their long-term success. Four "pillars" of sustainability are discussed based on
the experiences of EDM Forum grantees and other research and QI networks. These
include trust and value, governance, management, and financial and administrative
support. Two "foundational considerations," adaptive capacity and policy levers,
are also discussed.
PMID- 25848558
TI - eGEMs: An Opportunity for Better Science.
AB - eGEMs faces two early challenges in its effort to effort to disseminate knowledge
and new ideas about the use of electronic clinical data for research: attracting
readers and producing better science. The health services grey literature and the
microchip industry are two areas of knowledge generation that provide important
insight for how eGEMs can achieve these goals. In order to achieve its goals,
eGEMs should aim to promote rapid sharing of ideas, engage sponsors and potential
users of research findings early in the process, develop metrics for success to
guide research efforts, and recruit diverse contributors. Success would allow for
not just the generation of new research, but also new science, which has the
potential to significantly improve patient outcomes.
PMID- 25848559
TI - Security approaches in using tablet computers for primary data collection in
clinical research.
AB - Next-generation tablets (iPads and Android tablets) may potentially improve the
collection and management of clinical research data. The widespread adoption of
tablets, coupled with decreased software and hardware costs, has led to increased
consideration of tablets for primary research data collection. When using tablets
for the Washington Heights/Inwood Infrastructure for Comparative Effectiveness
Research (WICER) project, we found that the devices give rise to inherent
security issues associated with the potential use of cloud-based data storage
approaches. This paper identifies and describes major security considerations for
primary data collection with tablets; proposes a set of architectural strategies
for implementing data collection forms with tablet computers; and discusses the
security, cost, and workflow of each strategy. The paper briefly reviews the
strategies with respect to their implementation for three primary data collection
activities for the WICER project.
PMID- 25848560
TI - Development and Implementation of an Electronic Decision Support to Manage the
Health of a High-Risk Population: The enhanced Electronic Medical Record Aging
Brain Care Software (eMR-ABC).
AB - INTRODUCTION: Health care systems in the United States are transitioning from
volume-based purchasing models to value-based purchasing models that demand both
delivery of personalized care for each patient and cost-effective population
health management. The enhanced medical record for aging brain care (eMR-ABC)
software is an electronic decision support system that facilitates the management
of a high-risk population suffering from aging brain disorders such as dementia.
METHODS: Using the lenses of the Complex Adaptive System and the Reflective
Adaptive Process, we assembled an interdisciplinary team of clinicians, health
services researchers, and software developers who designed, implemented,
evaluated, and continuously modified the eMR-ABC to meet the needs of care
coordinators who manage the health of a targeted high-risk population. RESULTS:
The eMR-ABC captures and monitors the cognitive, functional, behavioral, and
psychological symptoms of a registry of patients suffering from dementia or
depression as well as the burden of patients' family caregivers. It provides
decision support to care coordinators to create a personalized care plan that
includes evidence-based nonpharmacological protocols, self-management handouts,
and alerts of medications with potentially adverse cognitive effects. The
software's built-in engine tracks patient visits and on-demand functionality to
generate population reports for specified indicators. DISCUSSION: Population
health programs depend on data collection and information systems with the
ability to provide valuable and timely feedback on an ongoing basis. Following
these guidelines, the eMR-ABC was designed specifically to meet the management
needs of a high-risk population.
PMID- 25848561
TI - Data warehouse governance programs in healthcare settings: a literature review
and a call to action.
AB - PURPOSE: Given the extensive data stored in healthcare data warehouses, data
warehouse governance policies are needed to ensure data integrity and privacy.
This review examines the current state of the data warehouse governance
literature as it applies to healthcare data warehouses, identifies knowledge
gaps, provides recommendations, and suggests approaches for further research.
METHODS: A comprehensive literature search using five data bases, journal article
title-search, and citation searches was conducted between 1997 and 2012. Data
warehouse governance documents from two healthcare systems in the USA were also
reviewed. A modified version of nine components from the Data Governance
Institute Framework for data warehouse governance guided the qualitative
analysis. RESULTS: Fifteen articles were retrieved. Only three were related to
healthcare settings, each of which addressed only one of the nine framework
components. Of the remaining 12 articles, 10 addressed between one and seven
framework components and the remainder addressed none. Each of the two data
warehouse governance plans obtained from healthcare systems in the USA addressed
a subset of the framework components, and between them they covered all nine.
CONCLUSIONS: While published data warehouse governance policies are rare, the 15
articles and two healthcare organizational documents reviewed in this study may
provide guidance to creating such policies. Additional research is needed in this
area to ensure that data warehouse governance polices are feasible and effective.
The gap between the development of data warehouses in healthcare settings and
formal governance policies is substantial, as evidenced by the sparse literature
in this domain.
PMID- 25848562
TI - Advances in Patient-Reported Outcomes: The NIH PROMIS((r)) Measures.
AB - Patient-reported outcomes (PRO) are questionnaire measures of patients' symptoms,
functioning, and health-related quality of life. They are designed to provide
important clinical information that generally cannot be captured with objective
medical testing. In 2004, the National Institutes of Health launched a research
initiative to improve the clinical research enterprise by developing state-of-the
art PROs. The NIH Patient-Reported Outcomes Measurement System (PROMIS) and
Assessment Center are the products of that initiative. Adult, pediatric, and
parent-proxy item banks have been developed by using contemporary psychometric
methods, yielding rapid, accurate measurements. PROMIS currently provides tools
for assessing physical, mental, and social health using short-form and computer
adaptive testing methods. The PROMIS tools are being adopted for use in clinical
trials and translational research. They are also being introduced in clinical
medicine to assess a broad range of disease outcomes. Recent legislative
developments in the United States support greater efforts to include patients'
reports of health experience in order to evaluate treatment outcomes, engage in
shared decision-making, and prioritize the focus of treatment. PROs have garnered
increased attention by the Food and Drug Administration (FDA) for evaluating
drugs and medical devices. Recent calls for comparative effectiveness research
favor inclusion of PROs. PROs could also potentially improve quality of care and
disease outcomes, provide patient-centered assessment for comparative
effectiveness research, and enable a common metric for tracking outcomes across
providers and medical systems.
PMID- 25848564
TI - Comparisons among Health Behavior Surveys: Implications for the Design of
Informatics Infrastructures That Support Comparative Effectiveness Research.
AB - INTRODUCTION: To address the electronic health data fragmentation that is a
methodological limitation of comparative effectiveness research (CER), the
Washington Heights Inwood Informatics Infrastructure for Comparative
Effectiveness Research (WICER) project is creating a patient-centered research
data warehouse (RDW) by linking electronic clinical data (ECD) from New York
Presbyterian Hospital's clinical data warehouse with ECD from ambulatory care,
long-term care, and home health settings and the WICER community health survey
(CHS). The purposes of the research were to identify areas of overlap between the
WICER CHS and two other surveys that include health behavior data (the Behavioral
Risk Factor Surveillance System (BRFSS) Survey and the New York City Community
Health Survey (NYC CHS)) and to identify gaps in the current WICER RDW that have
the potential to affect patient-centered CER. METHODS: We compared items across
the three surveys at the item and conceptual levels. We also compared WICER RDW
(ECD and WICER CHS), BRFSS, and NYC CHS to the County Health Ranking framework.
RESULTS: We found that 22 percent of WICER items were exact matches with BRFSS
and that there were no exact matches between WICER CHS and NYC CHS items not also
contained in BRFSS. CONCLUSIONS: The results suggest that BRFSS and, to a lesser
extent, NYC CHS have the potential to serve as population comparisons for WICER
CHS for some health behavior-related data and thus may be particularly useful for
considering the generalizability of CER study findings. Except for one measure
related to health behavior (motor vehicle crash deaths), the WICER RDW's
comprehensive coverage supports the mortality, morbidity, and clinical care
measures specified in the County Health Ranking framework but is deficient in
terms of some socioeconomic factors and descriptions of the physical environment
as captured in BRFSS. Linkage of these data in the WICER RDW through geocoding
can potentially facilitate patient-centered CER that integrates important
socioeconomic and physical environment influences on health outcomes. The
research methods and findings may be relevant to others interested in either
integrating health behavior data into RDWs to support patient-centered CER or
conducting population-level comparisons.
PMID- 25848563
TI - Recommendations for the use of operational electronic health record data in
comparative effectiveness research.
AB - There is an increasing amount of clinical data in operational electronic health
record (EHR) systems. Such data provide substantial opportunities for their re
use for many purposes, including comparative effectiveness research (CER). In a
previous paper, we identified a number of caveats related to the use of such
data, noting that they may be inaccurate, incomplete, transformed in ways that
undermine their meaning, unrecoverable for research, of unknown provenance, of
insufficient granularity, or incompatible with research protocols. In this paper,
we provide recommendations for overcoming these caveats with the goal of
leveraging such data to benefit CER and other health care activities. These
recommendations include adaptation of "best evidence" approaches to use of data;
processes to evaluate availability, completeness, quality, and transformability
of data; creation of tools to manage data and their attributes; determination of
metrics for assessing whether data are "research grade"; development of methods
for comparative validation of data; construction of a methodology database for
methods involving use of clinical data; standardized reporting methods for data
and their attributes; appropriate use of informatics expertise; and a research
agenda to determine biases inherent in operational data and to assess informatics
approaches to their improvement.
PMID- 25848565
TI - Preparing Electronic Clinical Data for Quality Improvement and Comparative
Effectiveness Research: The SCOAP CERTAIN Automation and Validation Project.
AB - BACKGROUND: The field of clinical research informatics includes creation of
clinical data repositories (CDRs) used to conduct quality improvement (QI)
activities and comparative effectiveness research (CER). Ideally, CDR data are
accurately and directly abstracted from disparate electronic health records
(EHRs), across diverse health-systems. OBJECTIVE: Investigators from Washington
State's Surgical Care Outcomes and Assessment Program (SCOAP) Comparative
Effectiveness Research Translation Network (CERTAIN) are creating such a CDR.
This manuscript describes the automation and validation methods used to create
this digital infrastructure. METHODS: SCOAP is a QI benchmarking initiative. Data
are manually abstracted from EHRs and entered into a data management system.
CERTAIN investigators are now deploying Caradigm's AmalgaTM tool to facilitate
automated abstraction of data from multiple, disparate EHRs. Concordance is
calculated to compare data automatically to manually abstracted. Performance
measures are calculated between Amalga and each parent EHR. Validation takes
place in repeated loops, with improvements made over time. When automated
abstraction reaches the current benchmark for abstraction accuracy - 95% - itwill
'go-live' at each site. PROGRESS TO DATE: A technical analysis was completed at
14 sites. Five sites are contributing; the remaining sites prioritized meeting
Meaningful Use criteria. Participating sites are contributing 15-18 unique data
feeds, totaling 13 surgical registry use cases. Common feeds are registration,
laboratory, transcription/dictation, radiology, and medications. Approximately
50% of 1,320 designated data elements are being automatically abstracted-25% from
structured data; 25% from text mining. CONCLUSION: In semi-automating data
abstraction and conducting a rigorous validation, CERTAIN investigators will semi
automate data collection to conduct QI and CER, while advancing the Learning
Healthcare System.
PMID- 25848566
TI - Advancing user experience research to facilitate and enable patient-centered
research: current state and future directions.
AB - Human-computer interaction and related areas of user experience (UX) research,
such as human factors, workflow evaluation, and data visualization, are thus
essential to presenting data in ways that can further the analysis of complex
data sets such as those used in patient-centered research. However, a review of
available data on the state of UX research as it relates to patient-centered
research demonstrates a significant underinvestment and consequently a large gap
in knowledge generation. In response, this report explores trends in funding and
research productivity focused on UX and patient-centered research and then
presents a set of recommendations to advance innovation at this important
intersection point. Ultimately, the aim is to catalyze a community-wide dialogue
concerning future directions for research and innovation in UX as it applies to
patient-centered research.
PMID- 25848568
TI - eGEMs: Pathways to Success for Multisite Clinical Data Research.
AB - There are numerous and significant challenges associated with leveraging
electronic clinical data (ECD) for purposes beyond treating an individual patient
and getting paid for that care. Optimizing this secondary use of clinical data is
a key underpinning of many health reform goals and triggers numerous issues
related to data stewardship and, more broadly, data governance. These challenges
often involve legal, policy, and procedural issues related to the access, use,
and disclosure of electronic health record (EHR) data for quality improvement and
research. This paper contributes to the ongoing discussion of health data
governance by detailing the experiences of nine multisite research initiatives
across the country. The rich set of experiences from these initiatives, as well
as a number of resources used by project participants to work through various
challenges, are documented and collected here for others wishing to learn from
their collective efforts. The paper does not attempt to catalog the full spectrum
of governance issues that could potentially surface in the course of multisite
research projects using ECD. Rather, the goal was to provide a snapshot in time
of data-sharing challenges and navigation strategies, as well as validation that
privacy-protective, legally compliant clinical data sharing across sites is
currently possible. Finally, the paper also provides a foundation and framing for
a broader community resource on governance-a "governance toolkit"-that will
create a virtual space for the further discussion and sharing of promising
practices.
PMID- 25848567
TI - Scalable Architecture for Federated Translational Inquiries Network (SAFTINet)
Technology Infrastructure for a Distributed Data Network.
AB - INTRODUCTION: Distributed Data Networks (DDNs) offer infrastructure solutions for
sharing electronic health data from across disparate data sources to support
comparative effectiveness research. Data sharing mechanisms must address
technical and governance concerns stemming from network security and data
disclosure laws and best practices, such as HIPAA. METHODS: The Scalable
Architecture for Federated Translational Inquiries Network (SAFTINet) deploys
TRIAD grid technology, a common data model, detailed technical documentation, and
custom software for data harmonization to facilitate data sharing in
collaboration with stakeholders in the care of safety net populations. Data
sharing partners host TRIAD grid nodes containing harmonized clinical data within
their internal or hosted network environments. Authorized users can use a central
web-based query system to request analytic data sets. DISCUSSION: SAFTINet DDN
infrastructure achieved a number of data sharing objectives, including scalable
and sustainable systems for ensuring harmonized data structures and terminologies
and secure distributed queries. Initial implementation challenges were resolved
through iterative discussions, development and implementation of technical
documentation, governance, and technology solutions.
PMID- 25848569
TI - Electronic Data Capture through Total Joint Replacement Registries.
AB - The move toward adoption and implementation of electronic health records (EHR)
provides an opportunity in the United States to use electronic clinical data
(ECD) to better understand patient outcomes and to improve the quality and
efficiency of medical care. Within the field of orthopedics, national joint
replacement registries have been shown in other countries to improve clinical
decision-making and outcomes after joint arthroplasty. Thus, there is increasing
interest among U.S. clinical investigators and policymakers to utilize ECD to
develop national and regional joint replacement registries. We discuss our
experience with integrating electronic data capture and reporting methodology
into the California Joint Replacement Registry and American Joint Replacement
Registry initiatives. The use of ECD for joint replacement registries will better
facilitate multi-stakeholder collaboration, improve the quality of care, reduce
medical spending, and foster customized evidence-based clinical decision-making.
PMID- 25848570
TI - Moving to a user-driven research paradigm.
AB - The traditional "bench-to-bedside" paradigm for clinical research has been
successfully used for many decades. This model of knowledge generation has led to
discoveries that have enhanced the quality and length of life. The combination of
changes in research practice and in health care delivery, growing complexity in
decision-making, increasing use of electronic health records (EHR), and growing
resource constraints necessitate a shift to a user-driven research paradigm to
generate new knowledge. This conceptual framework was created to clarify the
perspective of the decision makers as well as the range of factors and the
variability in thresholds used to make decisions. This framework may help
researchers in creating actionable information to meet the needs of decision
makers, which is needed for the transition to a user-driven research paradigm.
Further, it is important to create an appropriate set of incentives to facilitate
this transition to a user-driven research paradigm.
PMID- 25848571
TI - Applications of electronic health information in public health: uses,
opportunities & barriers.
AB - Electronic health information systems can reshape the practice of public health
including public health surveillance, disease and injury investigation and
control, decision making, quality assurance, and policy development. While these
opportunities are potentially transformative, and the federal program for the
Meaningful Use (MU) of electronic health records (EHRs) has included important
public health components, significant barriers remain. Unlike incentives in the
clinical care system, scant funding is available to public health departments to
develop the necessary information infrastructure and workforce capacity to
capitalize on EHRs, personal health records, or Big Data. Current EHR systems are
primarily built to serve clinical systems and practice rather than being
structured for public health use. In addition, there are policy issues concerning
how broadly the data can be used by public health officials. As these issues are
resolved and workable solutions emerge, they should yield a more efficient and
effective public health system.
PMID- 25848572
TI - Health-weighted Composite Quality Metrics Offer Promise to Improve Health
Outcomes in a Learning Health System.
AB - Health system leaders sometimes adopt quality metrics without robust supporting
evidence of improvements in quality and/or quantity of life, which may impair
rather than facilitate improved health outcomes. In brief, there is now no easy
way to measure how much "health" is conferred by a health system. However, we
argue that this goal is achievable. Health-weighted composite quality metrics
have the potential to measure "health" by synthesizing individual evidence-based
quality metrics into a summary measure, utilizing relative weightings that
reflect the relative amount of health benefit conferred by each constituent
quality metric. Previously, it has been challenging to create health-weighted
composite quality metrics because of methodological and data limitations.
However, advances in health information technology and mathematical modeling of
disease progression promise to help mitigate these challenges by making patient
level data (eg, from the electronic health record and mobile health (mHealth)
more accessible and more actionable for use. Accordingly, it may now be possible
to use health information technology to calculate and track a health-weighted
composite quality metric for each patient that reflects the health benefit
conferred to that patient by the health system. These health-weighted composite
quality metrics can be employed for a multitude of important aims that improve
health outcomes, including quality evaluation, population health maximization,
health disparity attenuation, panel management, resource allocation, and
personalization of care. We describe the necessary attributes, the possible uses,
and the likely limitations and challenges of health-weighted composite quality
metrics using patient-level health data.
PMID- 25848573
TI - How electronic clinical data can improve health technology assessment.
AB - Health technology assessments represent comprehensive summaries of available
evidence and information on a technology. They are used by medical decision
makers in a variety of ways, including diagnostic testing, treatment selection,
care management, patient perspectives, patient safety, insurance coverage,
pharmaceutical innovation, equipment planning, device purchasing, and total cost
of-care. Electronic clinical data, which are captured routinely by clinicians and
hospitals, are only rarely incorporated into formal health technology
assessments. This disconnect reveals a key opportunity. In this paper, we discuss
current uses of electronic clinical data, several benefits of including it in
health technology assessments, potential pitfalls of that inclusion, and the
implications for better medical decisions.
PMID- 25848574
TI - Achieving the Promise of Electronic Health Record-enabled Quality Measurement: a
Measure Developer's Perspective.
AB - Electronic health record (EHR) systems support local quality improvement efforts
by health care organizations and provide the opportunity to address national
priority areas for quality measurement, such as specialty care, overuse and
efficiency, coordination of care, change over time and patient- reported outcomes
(PROs). However, variations in provider workflow and documentation habits,
adoption of advanced EHR functions and exchange of interoperable data, and
eMeasure specification standards affect the ability to develop and test measures
that target these high priority areas for improvement. Measure developers are
working with providers, national standards organizations, and other eMeasure
stakeholders to address these challenges and support learning health
organizations in using EHR-based measurement to improve quality.
PMID- 25848575
TI - Ways decision makers can use evidence to improve patient outcomes in learning
health systems: a message from the guest editor.
PMID- 25848576
TI - Developing a fully integrated medical transport record to support comparative
effectiveness research for patients undergoing medical transport.
AB - The consolidation of health care systems to develop centers of clinical
excellence has led to an increased reliance on medical transport to move patients
requiring time-sensitive interventions and specialized treatments. There is a
paucity of outcomes data, specifically comparative effectiveness research,
related to the efficacy of different transport services and the overall morbidity
and mortality of patients that undergo medical transfer. The rapid development of
electronic medical record (EMR) use has also occurred with transport charting.
However, limited studies have incorporated transport chart data in outcomes
analyses. We have begun development of a fully integrated medical transport
record, combining transport and hospitals EMRs, to support research efforts and
develop clinical decision support tools for transported patients. In this paper,
we describe the elements necessary to develop a fully integrated medical
transport EMR to support the conduct of comparative effectiveness research,
outline the current limitations and challenges, and provide insight into the
future direction in developing clinical decision support tools for patients
requiring transport.
PMID- 25848577
TI - Medical home characteristics and asthma control: a prospective, observational
cohort study protocol.
AB - BACKGROUND: This paper describes the methods for an observational comparative
effectiveness research study designed to test the association between practice
level medical home characteristics and asthma control in children and adults
receiving care in safety-net primary care practices. METHODS: This is a
prospective, longitudinal cohort study, utilizing survey methodologies and
secondary analysis of existing structured clinical, administrative, and claims
data. The Scalable Architecture for Federated Translational Inquiries Network
(SAFTINet) is a safety net-oriented, primary care practice-based research
network, with federated databases containing electronic health record (EHR) and
Medicaid claims data. Data from approximately 20,000 patients from 50 practices
in four healthcare organizations will be included. Practice-level medical home
characteristics will be correlated with patient-level asthma outcomes,
controlling for potential confounding variables, using a clustered design. Linear
and non-linear mixed models will be used for analysis. Study inception was July
1, 2012. A causal graph theory approach was used to guide covariate selection to
control for bias and confounding. DISCUSSION: Strengths of this design include a
priori specification of hypotheses and methods, a large sample of patients with
asthma cared for in safety-net practices, the study of real-world variations in
the implementation of the medical home concept, and the innovative use of a
combination of claims data, patient-reported data, clinical data from EHRs, and
practice-level surveys. We address limitations in causal inference using theory,
design and analysis.
PMID- 25848579
TI - Using multifactorial experiments for comparative effectiveness research in
physician practices with electronic health record.
AB - Two key challenges related to conducting comparative effectiveness research are
the lack of available data and the lack of rigorous techniques for efficiently
and quickly testing the effectiveness of the many possible ways of implementing
components of care. The confluence of two things offers the promise of overcoming
these challenges: (1) the increased adoption of electronic health records (EHRs),
which can provide easier access to clinical information, and (2) burgeoning
appreciation for an under-used but powerful statistical research and evaluation
method for multifactor interventions known as multifactor experimental design.
The use of multifactorial experiments paired with EHR data has great potential to
help providers conduct rapid-cycle comparative effectiveness research and examine
alternative ways of implementing care. Its power is its ability to enable
scientifically rigorous testing of many facets of care provision simultaneously
in real-world settings where change is ongoing. In this paper, we identify the
opportunities for using efficient multifactorial designs and EHR data to evaluate
quality-improvement efforts in physician practices. We illustrate the power of
multifactorial designs through several examples relevant to physician practices
with EHRs, such as evaluating clinical decision support features and studying
components of a patient-centered medical home.
PMID- 25848578
TI - Strategies for handling missing data in electronic health record derived data.
AB - Electronic health records (EHRs) present a wealth of data that are vital for
improving patient-centered outcomes, although the data can present significant
statistical challenges. In particular, EHR data contains substantial missing
information that if left unaddressed could reduce the validity of conclusions
drawn. Properly addressing the missing data issue in EHR data is complicated by
the fact that it is sometimes difficult to differentiate between missing data and
a negative value. For example, a patient without a documented history of heart
failure may truly not have disease or the clinician may have simply not
documented the condition. Approaches for reducing missing data in EHR systems
come from multiple angles, including: increasing structured data documentation,
reducing data input errors, and utilization of text parsing / natural language
processing. This paper focuses on the analytical approaches for handling missing
data, primarily multiple imputation. The broad range of variables available in
typical EHR systems provide a wealth of information for mitigating potential
biases caused by missing data. The probability of missing data may be linked to
disease severity and healthcare utilization since unhealthier patients are more
likely to have comorbidities and each interaction with the health care system
provides an opportunity for documentation. Therefore, any imputation routine
should include predictor variables that assess overall health status (e.g.
Charlson Comorbidity Index) and healthcare utilization (e.g. number of
encounters) even when these comorbidities and patient encounters are unrelated to
the disease of interest. Linking the EHR data with other sources of information
(e.g. National Death Index and census data) can also provide less biased
variables for imputation. Additional methodological research with EHR data and
improved epidemiological training of clinical investigators is warranted.
PMID- 25848580
TI - Methods for estimating kidney disease stage transition probabilities using
electronic medical records.
AB - Chronic diseases are often described by stages of severity. Clinical decisions
about what to do are influenced by the stage, whether a patient is progressing,
and the rate of progression. For chronic kidney disease (CKD), relatively little
is known about the transition rates between stages. To address this, we used
electronic health records (EHR) data on a large primary care population, which
should have the advantage of having both sufficient follow-up time and sample
size to reliably estimate transition rates for CKD. However, EHR data have some
features that threaten the validity of any analysis. In particular, the timing
and frequency of laboratory values and clinical measurements are not determined a
priori by research investigators, but rather, depend on many factors, including
the current health of the patient. We developed an approach for estimating CKD
stage transition rates using hidden Markov models (HMMs), when the level of
information and observation time vary among individuals. To estimate the HMMs in
a computationally manageable way, we used a "discretization" method to transform
daily data into intervals of 30 days, 90 days, or 180 days. We assessed the
accuracy and computation time of this method via simulation studies. We also used
simulations to study the effect of informative observation times on the estimated
transition rates. Our simulation results showed good performance of the method,
even when missing data are non-ignorable. We applied the methods to EHR data from
over 60,000 primary care patients who have chronic kidney disease (stage 2 and
above). We estimated transition rates between six underlying disease states. The
results were similar for men and women.
PMID- 25848581
TI - New analytical methods for a learning healthcare system: a message from the guest
editor.
PMID- 25848582
TI - Validation of Diagnostic and Procedural Codes for Identification of Acute
Cardiovascular Events in US Veterans with Rheumatoid Arthritis.
AB - OBJECTIVE: To assess the accuracy of International Classification of Diseases,
Ninth Revision, and Current Procedural Terminology codes for identifying
cardiovascular (CV) events (myocardial infarction [MI], stroke, coronary artery
bypass graft [CABG], and percutaneous coronary intervention [PCI]) in enrollees
of the Veterans Affairs Rheumatoid Arthritis (VARA) registry. DESIGN: We
performed a validation study from VARA enrollment until 6/1/2010 to compare the
accuracy of CV events in those with and without CV-event coding in inpatient and
outpatient records to evaluate for CV events +/- 3 months of the coding. The
positive predictive value (PPV) was calculated, and codes with a PPV >=50% were
included in a composite coding algorithm. RESULTS: We evaluated 107 individuals
for 21 CV-event codes and 60 individuals without CV-event coding. The PPV varied
between 0-100%. Composite coding algorithms' PPV ranged from 70-100%.
CONCLUSIONS: Validation of these algorithms allows for identification of acute CV
events with known accuracy. The sensitivity and PPV of coding algorithms for CABG
and PCI exceed that of stroke and MI.
PMID- 25848583
TI - A case study of pediatric asthma alerts from the beacon community program in
cincinnati: technology is just the first step.
AB - INTRODUCTION: The Beacon Community in Cincinnati, Ohio was an innovative,
community-wide initiative to use technology to transform care. One important
feature was the development of regional alerts to notify practices when patients
were hospitalized or seen in the emergency department. The purpose of this paper
is to describe the way in which technology engages the improvement process, and
to describe the early stages of learning how to use technology to enhance quality
improvement. METHODS: We interviewed key Beacon leaders as well as providers and
office staff in selected practices. We also collected preliminary data from
practices that reflected handling of alerts, including the number of asthma
related alerts received and followed up. RESULTS: Regional alerts, supplied by
the community-wide health information exchange, were a significant addition to
the quality improvement effort in that they enabled practices to identify and
follow up with additional children at risk. An important finding was the
substantial effort at the practice level to integrate technology into ongoing
patient care. CONCLUSIONS: Developing the technology for community wide alerts
represented a significant endeavor in the Cincinnati Beacon Community. However,
the technology was just the first step. Despite extra effort and time required on
the part of individual practices, they reported that the value of having alerts
was high. Hospital and ED visits represent some of the most costly aspects of
care, and an efficient process for intervening with children using these costly
services was seen as of significant value.
PMID- 25848585
TI - Validity of medical chart weights and heights for obese pregnant women.
AB - OBJECTIVE: To determine the validity of adult body weights and heights recorded
in electronic medical records (EMRs) in the course of routine medical care.
BACKGROUND: EMRs allow the potential use of data collected in the course of
routine medical care for a variety of research applications in many fields
including epidemiology and comparative effectiveness studies. However,
researchers familiar with carefully controlled measurement protocols typically
used in clinical trials may question the validity of data collected in the course
of routine clinical care. METHODS: Weights and heights collected during a
research project that focused on weight gain during pregnancy were compared to
weight and height measurements coincidently recorded in the research
participant's medical records. For weight measures (N=102), data recorded within
+/-14 days were compared, and for height measures (N=114), data recorded within
+/-5 years were compared. We assessed agreement between medical and research
measurements using the concordance and intraclass correlation coefficients, and
Bland and Altman's limits of agreement. FINDINGS: The mean research and medical
record weight measurements were 99.3 kg and 99.2 kg, respectively. The
concordance and intraclass correlation coefficients for weight had similar
estimates of .999 and 95 percent confidence intervals [.998, .999]. The 95
percent limits of agreement were -1.5 kg and +1.7 kg. The mean research and
medical height measurements were 1.646 m and 1.654 m, respectively, and the
concordance and intraclass correlation coefficients for height were .941 and
.942, respectively. The 95 percent limits of agreement were -.031 m and +.047 m.
CONCLUSIONS: For pregnant women, body weights documented in the medical record
are exchangeable with body weights recorded in a research setting. Height
measurements recorded in the medical records were not in as close agreement as
weights, but concordance between medical record and research height measurements
are high enough to allow them to be used epidemiological and comparative
effectiveness research.
PMID- 25848584
TI - The HMO Research Network Virtual Data Warehouse: A Public Data Model to Support
Collaboration.
AB - The HMO Research Network (HMORN) Virtual Data Warehouse (VDW) is a public, non
proprietary, research-focused data model implemented at 17 health care systems
across the United States. The HMORN has created a governance structure and
specified policies concerning the VDW's content, development, implementation, and
quality assurance. Data extracted from the VDW have been used by thousands of
studies published in peer-reviewed journal articles. Advances in software
supporting care delivery and claims processing and the availability of new data
sources have greatly expanded the data available for research, but substantially
increased the complexity of data management. The VDW data model incorporates
software and data advances to ensure that comprehensive, up-to-date data of known
quality are available for research. VDW governance works to accommodate new data
and system complexities. This article highlights the HMORN VDW data model, its
governance principles, data content, and quality assurance procedures. Our goal
is to share the VDW data model and its operations to those wishing to implement a
distributed interoperable health care data system.
PMID- 25848586
TI - Development of a web service for analysis in a distributed network.
AB - OBJECTIVE: We describe functional specifications and practicalities in the
software development process for a web service that allows the construction of
the multivariate logistic regression model, Grid Logistic Regression (GLORE), by
aggregating partial estimates from distributed sites, with no exchange of patient
level data. BACKGROUND: We recently developed and published a web service for
model construction and data analysis in a distributed environment. This recent
paper provided an overview of the system that is useful for users, but included
very few details that are relevant for biomedical informatics developers or
network security personnel who may be interested in implementing this or similar
systems. We focus here on how the system was conceived and implemented. METHODS:
We followed a two-stage development approach by first implementing the backbone
system and incrementally improving the user experience through interactions with
potential users during the development. Our system went through various stages
such as concept proof, algorithm validation, user interface development, and
system testing. We used the Zoho Project management system to track tasks and
milestones. We leveraged Google Code and Apache Subversion to share code among
team members, and developed an applet-servlet architecture to support the cross
platform deployment. DISCUSSION: During the development process, we encountered
challenges such as Information Technology (IT) infrastructure gaps and limited
team experience in user-interface design. We figured out solutions as well as
enabling factors to support the translation of an innovative privacy-preserving,
distributed modeling technology into a working prototype. CONCLUSION: Using GLORE
(a distributed model that we developed earlier) as a pilot example, we
demonstrated the feasibility of building and integrating distributed modeling
technology into a usable framework that can support privacy-preserving,
distributed data analysis among researchers at geographically dispersed
institutes.
PMID- 25848587
TI - Medicaid medical directors quality improvement studies: a case study of evolving
methods for a research network.
AB - OBJECTIVE: To describe the evolution of methods and share lessons learned from
conducting multi-state studies with Medicaid Medical Directors (MMD) using state
administrative data. There was a great need for these studies, but also much to
be learned about conducting network-based research and ensuring comparability of
results. METHODS: This was a network-level case study. The findings were drawn
from the experience developing and executing network analyses with the MMDs, as
well as from participant feedback on lessons learned. For the latter, nine
interviews with MMD project leads, state data analysts, and outside researchers
involved with the projects were conducted. Interviews were transcribed, coded and
analyzed using NVivo 10.0 analytic software. FINDINGS: MMD study methodology
involved many steps: developing research questions, defining data specifications,
organizing an aggregated data collection spreadsheet form, assuring quality
through review, and analyzing and reporting state data at the national level.
State analysts extracted the data from their state Medicaid administrative
(claims) databases (and sometimes other datasets). Analysis at the national level
aggregated state data overall, by demographics and other sub groups, and
displayed descriptive statistics and cross-tabs. CONCLUSIONS: Projects in the MMD
multi-state network address high-priority clinical issues in Medicaid and impact
quality of care through sharing of data and policies among states. Further, these
studies contribute not only to high-quality, cost-effective health care for
Medicaid beneficiaries, but also add to our knowledge of network-based research.
Continuation of these studies requires funding for a permanent research
infrastructure nationally, as well as at the state-level to strengthen capacity.
PMID- 25848588
TI - Electronic Clinical Surveillance to Improve Outpatient Care: Diverse Applications
within an Integrated Delivery System.
AB - Efforts to improve patient safety have largely focused on inpatient or emergency
settings, but the importance of patient safety in ambulatory care is increasingly
being recognized as a key component of overall health care quality. Care gaps in
outpatient settings may include missed diagnoses, medication errors, or
insufficient monitoring of patients with chronic conditions or on certain
medications. Further, care gaps may occur across a wide range of clinical
conditions. We report here an innovative approach to improve patient safety in
ambulatory settings - the Kaiser Permanente Southern California (KPSC) Outpatient
Safety Net Program - which leverages electronic health information to efficiently
identify and address a variety of potential care gaps across different clinical
conditions. Between 2006 and 2012, the KPSC Outpatient Safety Net Program
implemented 24 distinct electronic clinical surveillance programs, which
routinely scan the electronic health record to identify patients with a
particular condition or event. For example, electronic clinical surveillance may
be used to scan for harmful medication interactions or potentially missed
diagnoses (e.g., abnormal test results without evidence of subsequent care). Keys
to the success of the program include strong leadership support, a proactive
clinical culture, the blame-free nature of the program, and the availability of
electronic health information. The Outpatient Safety Net Program framework may be
adopted by other organizations, including those who have electronic health
information but not an electronic health record. In the future, the creation of a
forum to share electronic clinical surveillance programs across organizations may
facilitate more rapid improvements in outpatient safety.
PMID- 25848589
TI - Data governance and data sharing agreements for community-wide health information
exchange: lessons from the beacon communities.
AB - PURPOSE: Unprecedented efforts are underway across the United States to
electronically capture and exchange health information to improve health care and
population health, and reduce costs. This increased collection and sharing of
electronic patient data raises several governance issues, including privacy,
security, liability, and market competition. Those engaged in such efforts have
had to develop data sharing agreements (DSAs) among entities involved in
information exchange, many of whom are "nontraditional" health care entities
and/or new partners. This paper shares lessons learned based on the experiences
of six federally funded communities participating in the Beacon Community
Cooperative Agreement Program, and offers guidance for navigating data governance
issues and developing DSAs to facilitate community-wide health information
exchange. INNOVATION: While all entities involved in electronic data sharing must
address governance issues and create DSAs accordingly, until recently little
formal guidance existed for doing so - particularly for community-based
initiatives. Despite this lack of guidance, together the Beacon Communities'
experiences highlight promising strategies for navigating complex governance
issues, which may be useful to other entities or communities initiating
information exchange efforts to support delivery system transformation.
CREDIBILITY: For the past three years, AcademyHealth has provided technical
assistance to most of the 17 Beacon Communities, 6 of whom contributed to this
collaborative writing effort. Though these communities varied widely in terms of
their demographics, resources, and Beacon-driven priorities, common themes
emerged as they described their approaches to data governance and DSA
development. CONCLUSIONS: The 6 Beacon Communities confirmed that DSAs are
necessary to satisfy legal and market-based concerns, and they identified several
specific issues, many of which have been noted by others involved in network data
sharing initiatives. More importantly, these communities identified several
promising approaches to timely and effective DSA development, including:
stakeholder engagement; identification and effective communication of value;
adoption of a parsimonious approach; attention to market-based concerns;
flexibility in adapting and expanding existing agreements and partnerships; and
anticipation of required time and investment.
PMID- 25848590
TI - The COMET Sleep Research Platform.
AB - INTRODUCTION: The Comparative Outcomes Management with Electronic Data Technology
(COMET) platform is extensible and designed for facilitating multicenter
electronic clinical research. BACKGROUND: Our research goals were the following:
(1) to conduct a comparative effectiveness trial (CET) for two obstructive sleep
apnea treatments-positive airway pressure versus oral appliance therapy; and (2)
to establish a new electronic network infrastructure that would support this
study and other clinical research studies. DISCUSSION: The COMET platform was
created to satisfy the needs of CET with a focus on creating a platform that
provides comprehensive toolsets, multisite collaboration, and end-to-end data
management. The platform also provides medical researchers the ability to
visualize and interpret data using business intelligence (BI) tools. CONCLUSION:
COMET is a research platform that is scalable and extensible, and which, in a
future version, can accommodate big data sets and enable efficient and effective
research across multiple studies and medical specialties. The COMET platform
components were designed for an eventual move to a cloud computing infrastructure
that enhances sustainability, overall cost effectiveness, and return on
investment.
PMID- 25848591
TI - Learning from health information exchange technical architecture and
implementation in seven beacon communities.
AB - As health care providers adopt and make "meaningful use" of health information
technology (health IT), communities and delivery systems must set up the
infrastructure to facilitate health information exchange (HIE) between providers
and numerous other stakeholders who have a role in supporting health and care. By
facilitating better communication and coordination between providers, HIE has the
potential to improve clinical decision-making and continuity of care, while
reducing unnecessary use of services. When implemented as part of a broader
strategy for health care delivery system and payment reform, HIE capability also
can enable the use of analytic tools needed for population health management,
patient engagement in care, and continuous learning and improvement. The diverse
experiences of seven communities that participated in the three-year federal
Beacon Community Program offer practical insight into factors influencing the
technical architecture of exchange infrastructure and its role in supporting
improved care, reduced cost, and a healthier population. The case studies also
document challenges faced by the communities, such as significant time and
resources required to harmonize variations in the interpretation of data
standards. Findings indicate that their progress developing community-based HIE
strategies, while driven by local needs and objectives, is also influenced by
broader legal, policy, and market conditions.
PMID- 25848592
TI - Importance of the medicaid medical directors' multistate collaborative for
improving care in medicaid.
AB - INTRODUCTION: There are many benefits of multistate collaboratives or networks to
states, but at the center is that they allow for the opportunity to learn from
other states and experts about the practices and policies states have implemented
without the significant time lag of published research. This commentary examines
these benefits and illustrates the importance of quality improvement
collaborations to decision-making in state Medicaid programs. BACKGROUND: In
2007, the Medicaid Medical Directors Learning Network (MMDLN) began conducting
quality improvement studies using their own state-level administrative data to
better understand the major clinical issues facing the Medicaid populations and
to work together on policies to improve outcomes. RATIONALE AND RESULTS: The
three issues selected by MMDs for quality improvement monitoring to date involved
an important national problem - including both morbidity and cost - and were
amenable to policy solutions. The studies examined the use of antipsychotic
medication in children, hospital admissions and readmissions, and early elective
deliveries (i.e., elective deliveries occurring before 39 weeks). IMPORTANCE AND
UTILITY: The multistate clinical quality projects conducted offer a key mechanism
for achieving the goal of helping the Medicaid program deliver value-driven, high
quality, cost-effective health care in an efficient manner. These projects also
provide the participating states with data to inform policies internally.
CONCLUSIONS: In order for the quality of health care to improve, the system needs
to be structured as a learning health care system; one that is always accessing
evidence, implementing a variation of it (i.e., with new data sources or tools
such as electronic clinical data), assessing effectiveness, and sharing results
for others to repeat the cycle.
PMID- 25848593
TI - Accelerating regulatory progress in multi-institutional research.
AB - PURPOSE: Multi-institutional collaborations are necessary in order to create
large and robust data sets that are needed to answer important comparative
effectiveness research (CER) questions. Before scientific work can begin, a
complex maze of administrative and regulatory requirements must be efficiently
navigated to avoid project delays. INNOVATION: Staff from research, regulatory,
and administrative teams involved in three HMO Research Network (HMORN) multi
institutional collaborations developed and employed novel approaches: to secure
and maintain Institutional Review Board (IRB) approvals; to enable data sharing,
and to expedite subawards for two data-only minimal risk studies. These novel
approaches accelerated required processes and approvals while maintaining
regulatory, human subjects, and institutional protections. CREDIBILITY: Outcomes
from the processes described here are compared with processes outlined in the
research and regulatory literature and with processes that have been used in
previous multisite research collaborations. CONCLUSION AND DISCUSSION: Research,
regulatory, and administrative staff are essential contributors to the success of
multi-institutional collaborations. Their flexibility, creativity, and effective
communication skills can lead to the development of efficient approaches to
achieving the necessary oversight for these complex projects. Elements of these
specific strategies can be adapted and used by other research networks. Other
efforts in these areas should be evaluated and shared. The processes that help
develop a "learning research system" play an important and complementary role in
sustaining multi-institutional research collaborations.
PMID- 25848594
TI - Availability of structured and unstructured clinical data for comparative
effectiveness research and quality improvement: a multisite assessment.
AB - INTRODUCTION: A key attribute of a learning health care system is the ability to
collect and analyze routinely collected clinical data in order to quickly
generate new clinical evidence, and to monitor the quality of the care provided.
To achieve this vision, clinical data must be easy to extract and stored in
computer readable formats. We conducted this study across multiple organizations
to assess the availability of such data specifically for comparative
effectiveness research (CER) and quality improvement (QI) on surgical procedures.
SETTING: This study was conducted in the context of the data needed for the
already established Surgical Care and Outcomes Assessment Program (SCOAP), a
clinician-led, performance benchmarking, and QI registry for surgical and
interventional procedures in Washington State. METHODS: We selected six
hospitals, managed by two Health Information Technology (HIT) groups, and
assessed the ease of automated extraction of the data required to complete the
SCOAP data collection forms. Each data element was classified as easy, moderate,
or complex to extract. RESULTS: Overall, a significant proportion of the data
required to automatically complete the SCOAP forms was not stored in structured
computer-readable formats, with more than 75 percent of all data elements being
classified as moderately complex or complex to extract. The distribution differed
significantly between the health care systems studied. CONCLUSIONS: Although
highly desirable, a learning health care system does not automatically emerge
from the implementation of electronic health records (EHRs). Innovative methods
to improve the structured capture of clinical data are needed to facilitate the
use of routinely collected clinical data for patient phenotyping.
PMID- 25848595
TI - The visit-data warehouse: enabling novel secondary use of health information
exchange data.
AB - INTRODUCTION/OBJECTIVES: Health Information Exchange (HIE) efforts face
challenges with data quality and performance, and this becomes especially
problematic when data is leveraged for uses beyond primary clinical use. We
describe a secondary data infrastructure focusing on patient-encounter,
nonclinical data that was built on top of a functioning HIE platform to support
novel secondary data uses and prevent potentially negative impacts these uses
might have otherwise had on HIE system performance. BACKGROUND: HIE efforts have
generally formed for the primary clinical use of individual clinical providers
searching for data on individual patients under their care, but many secondary
uses have been proposed and are being piloted to support care management, quality
improvement, and public health. DESCRIPTION OF THE HIE AND BASE INFRASTRUCTURE:
This infrastructure review describes a module built into the Healthix HIE.
Healthix, based in the New York metropolitan region, comprises 107 participating
organizations with 29,946 acute-care beds in 383 facilities, and includes more
than 9.2 million unique patients. The primary infrastructure is based on the
InterSystems proprietary Cache data model distributed across servers in multiple
locations, and uses a master patient index to link individual patients' records
across multiple sites. We built a parallel platform, the "visit data warehouse,"
of patient encounter data (demographics, date, time, and type of visit) using a
relational database model to allow accessibility using standard database tools
and flexibility for developing secondary data use cases. These four secondary use
cases include the following: (1) tracking encounter-based metrics in a newly
established geriatric emergency department (ED), (2) creating a dashboard to
provide a visual display as well as a tabular output of near-real-time de
identified encounter data from the data warehouse, (3) tracking frequent ED users
as part of a regional-approach to case management intervention, and (4) improving
an existing quality improvement program that analyzes patients with return visits
to EDs within 72 hours of discharge. RESULTS/LESSONS LEARNED: Setting up a
separate, near-real-time, encounters-based relational database to complement an
HIE built on a hierarchical database is feasible, and may be necessary to support
many secondary uses of HIE data. As of November 2014, the visit-data warehouse
(VDW) built by Healthix is undergoing technical validation testing and updates on
an hourly basis. We had to address data integrity issues with both nonstandard
and missing HL7 messages because of varied HL7 implementation across the HIE.
Also, given our HIEs federated structure, some sites expressed concerns regarding
data centralization for the VDW. An established and stable HIE governance
structure was critical in overcoming this initial reluctance. CONCLUSIONS: As
secondary use of HIE data becomes more prevalent, it may be increasingly
necessary to build separate infrastructure to support secondary use without
compromising performance. More research is needed to determine optimal ways of
building such infrastructure and validating its use for secondary purposes.
PMID- 25848596
TI - Patient report improves posthospital discharge event capture in total joint
replacement: a novel approach to capturing all posthospital event data.
AB - INTRODUCTION: Current approaches to quantifying total posthospital complications
and readmissions following surgical procedures are limited because the United
States does not have a single health care payer. Patients seek posthospital care
in varied locations, yet hospitals can only quantify those returning to the same
facility. Seeking information directly from patients about health care
utilization following hospital discharge holds promise to provide data that is
missing for surgeons and health care systems. BACKGROUND: Because total joint
replacement (TJR) is the most common and costly elective surgical
hospitalization, we examined the concordance between patients' self-report of
potential short-term complications and their readmissions and our review of
medical records in the initial hospital and surrounding facilities. METHODS:
Patients undergoing primary total hip or knee replacement from July 1, 2011,
through December 3, 2012, at a large site participating in a national cohort of
TJR patients were identified. Patients completed a six-month postoperative survey
regarding emergency department (ED), day surgery (DS), or inpatient care for
possible medical or mechanical post-TJR complications. We reviewed inpatient and
outpatient medical records from all regional facilities and examined the
sensitivity, specificity, and positive- and negative predictive values for
patient self-report and medical records. FINDINGS: There were 413 patients who
had 431 surgeries and completed the six-month questionnaire. Patients reported 40
medical encounters (9 percent) including ED, DS or inpatient care, of which 20
percent occurred at hospitals different from the initial surgery. Review of
medical records revealed 9 additional medical encounters that patients had not
mentioned including five hospitalizations following surgery and four ED visits.
Overall patient self-report of ED, DS, and inpatient care for possible
complications was both sensitive (82 percent) and specific (100 percent). The
positive predictive value was 100 percent and negative predictive value 98
percent. DISCUSSION: Patient self-report of posthospital events was accurate.
Substantial numbers of patients required care at outlying hospitals (not where
the TJR occurred). CONCLUSION: Methods that directly engage patients can augment
current posthospital utilization surveillance to assure complete data.
PMID- 25848597
TI - Transforming the Premier Perspective Hospital Database into the Observational
Medical Outcomes Partnership (OMOP) Common Data Model.
AB - BACKGROUND: The Observational Medical Outcomes Partnership (OMOP) Common Data
Model (CDM) has been implemented on various claims and electronic health record
(EHR) databases, but has not been applied to a hospital transactional database.
This study addresses the implementation of the OMOP CDM on the U.S. Premier
Hospital database. METHODS: We designed and implemented an extract, transform,
load (ETL) process to convert the Premier hospital database into the OMOP CDM.
Standard charge codes in Premier were mapped between the OMOP version 4.0
Vocabulary and standard charge descriptions. Visit logic was added to impute the
visit dates. We tested the conversion by replicating a published study using the
raw and transformed databases. The Premier hospital database was compared to a
claims database, in regard to prevalence of disease. FINDINGS: The data
transformed into the CDM resulted in 1% of the data being discarded due to data
errors in the raw data. A total of 91.4% of Premier standard charge codes were
mapped successfully to a standard vocabulary. The results of the replication
study resulted in a similar distribution of patient characteristics. The
comparison to the claims data yields notable similarities and differences amongst
conditions represented in both databases. DISCUSSION: The transformation of the
Premier database into the OMOP CDM version 4.0 adds value in conducting analyses
due to successful mapping of the drugs and procedures. The addition of visit
logic gives ordinality to drugs and procedures that wasn't present prior to the
transformation. Comparing conditions in Premier against a claims database can
provide an understanding about Premier's potential use in pharmacoepidemiology
studies that are traditionally conducted via claims databases. CONCLUSION AND
NEXT STEPS: The conversion of the Premier database into the OMOP CDM 4.0 was
completed successfully. The next steps include refinement of vocabularies and
mappings and continual maintenance of the transformed CDM.
PMID- 25848598
TI - Automating data abstraction in a quality improvement platform for surgical and
interventional procedures.
AB - OBJECTIVE: This paper describes a text processing system designed to automate the
manual data abstraction process in a quality improvement (QI) program. The
Surgical Care and Outcomes Assessment Program (SCOAP) is a clinician-led,
statewide performance benchmarking QI platform for surgical and interventional
procedures. The data elements abstracted as part of this program cover a wide
range of clinical information from patient medical history to details of surgical
interventions. METHODS: Statistical and rule-based extractors were developed to
automatically abstract data elements. A preprocessing pipeline was created to
chunk free-text notes into its sections, sentences, and tokens. The information
extracted in this preprocessing step was used by the statistical and rule-based
extractors as features. FINDINGS: Performance results for 25 extractors (14
statistical, 11 rule based) are presented. The average f1-scores for 11 rule
based extractors and 14 statistical extractors are 0.785 (min=0.576,max=0.931,std
dev=0.113) and 0.812 (min=0.571,max=0.993,std-dev=0.135) respectively.
DISCUSSION: Our error analysis revealed that most extraction errors were due
either to data imbalance in the data set or the way the gold standard had been
created. CONCLUSION: As future work, more experiments will be conducted with a
more comprehensive data set from multiple institutions contributing to the QI
project.
PMID- 25848599
TI - Modifying the electronic health record to facilitate the implementation and
evaluation of a bundled care program for intensive care unit delirium.
AB - CONTEXT: Electronic health records (EHRs) have been promoted as a key driver of
improved patient care and outcomes and as an essential component of learning
health systems. However, to date, many EHRs are not optimized to support delivery
of quality and safety initiatives, particularly in Intensive Care Units (ICUs).
Delirium is a common and severe problem for ICU patients that may be prevented or
mitigated through the use of evidence-based care processes (daily awakening and
breathing trials, formal delirium screening, and early mobility-collectively
known as the "ABCDE bundle"). This case study describes how an integrated health
care delivery system modified its inpatient EHR to accelerate the implementation
and evaluation of ABCDE bundle deployment as a safety and quality initiative.
CASE DESCRIPTION: In order to facilitate uptake of the ABCDE bundle and measure
delivery of the care processes within the bundle, we worked with clinical and
technical experts to create structured data fields for documentation of bundle
elements and to identify where these fields should be placed within the EHR to
streamline staff workflow. We created an "ABCDE" tab in the existing patient
viewer that allowed providers to easily identify which components of the bundle
the patient had and had not received. We examined the percentage of ABCDE bundle
elements captured in these structured data fields over time to track compliance
with data entry procedures and to improve documentation of care processes. MAJOR
THEMES: Modifying the EHR to support ABCDE bundle deployment was a complex and
time-consuming process. We found that it was critical to gain buy-in from senior
leadership on the importance of the ABCDE bundle to secure information technology
(IT) resources, understand the different workflows of members of
multidisciplinary care teams, and obtain continuous feedback from staff on the
EHR revisions during the development cycle. We also observed that it was
essential to provide ongoing training to staff on proper use of the new EHR
documentation fields. Lastly, timely reporting on ABCDE bundle performance may be
essential to improved practice adoption and documentation of care processes.
CONCLUSION: The creation of learning health systems is contingent on an ability
to modify EHRs to meet emerging care delivery and quality improvement needs.
Although this study focuses on the prevention and mitigation of delirium in ICUs,
our process for identifying key data elements and making modifications to the
EHR, as well as the lessons learned from the IT components of this program, are
generalizable to other health care settings and conditions.
PMID- 25848600
TI - Developing electronic data methods infrastructure to participate in collaborative
research networks.
AB - CONTEXT: Collaborative networks support the goals of a learning health system by
sharing, aggregating, and analyzing data to facilitate identification of best
practices care across delivery organizations. This case study describes the
infrastructure and process developed by an integrated health delivery system to
successfully prepare and submit a complex data set to a large national
collaborative network. CASE DESCRIPTION: We submitted four years of data for a
diverse population of patients in specific clinical areas: diabetes, chronic
heart failure, sepsis, and hip, knee, and spine. The most recent submission
included 19 tables, more than 376,000 unique patients, and almost 5 million
patient encounters. Data was extracted from multiple clinical and administrative
systems. LESSONS LEARNED: We found that a structured process with documentation
was key to maintaining communication, timelines, and quality in a large-scale
data submission to a national collaborative network. The three key components of
this process were the experienced project team, documentation, and communication.
We used a formal QA and feedback process to track and review data. Overall, the
data submission was resource intensive and required an incremental approach to
data quality. CONCLUSION: Participation in collaborative networks can be time and
resource intense, however it can serve as a catalyst to increase the technical
data available to the learning health system.
PMID- 25848601
TI - Web-based Comparative Patient-reported Outcome Feedback to Support Quality
Improvement and Comparative Effectiveness Research in Total Joint Replacement.
AB - INTRODUCTION: Patient-reported outcomes (PROs) are rarely included in quality
monitoring systems, surgeon comparative feedback reports, or registries. We
present the design and implementation of a secure website in a federally funded
research program-Function and Outcomes Research for Comparative Effectiveness in
Total Joint Replacement (FORCE-TJR)-to return comparative PRO reports to
participating surgeons, in addition to including traditional quality measures, in
order to monitor and improve quality and health outcomes. METHODS: The surgeon
specific comparative PRO reports were designed and structured based on user input
for content, data elements, integration, and display. Three questions are
addressed regarding the knee and hip joint symptom profiles of patients before
TJR, as well as outcomes of surgery. The website is organized with a hierarchical
structure to display data at national, practice, and individual surgeon levels,
and provides a comprehensive site-level executive summary and surgeon-level data
reports that can be downloaded. EARLY RESULTS: As of September 2014, over 22,000
patients were enrolled from more than 130 surgeons in 22 states. The reporting
website was launched in September 2012 and has been updated quarterly for all
surgeons to review their site- and individual-specific outcomes data compared to
national benchmarks. DISCUSSION: In this novel system, quarterly comparative
surgeon feedback extends beyond traditional measures of complication rates to
include PROs of pain relief and functional gain. We anticipate that this enhanced
data will facilitate patient-centered quality improvement (QI) and outcomes
research from the registry. As the Centers for Medicare & Medicaid Services (CMS)
and other insurers consider future implementation of PROs, surgeons will
increasingly need comparative data by which to self-monitor their practice
outcomes.
PMID- 25848602
TI - eGEMs' Early Adventures in Open Access Publishing.
AB - INTRODUCTION: In January 2013 AcademyHealth officially launched eGEMs (Generating
Evidence and Methods to improve patient outcomes) to rapidly disseminate peer
reviewed approaches using electronic health data (EHD) to advance research and
quality improvement (QI), with the overall goal of improving patient and
community outcomes. Inspired by the publication of eGEMs 50(th) paper, Dr. Erin
Holve, eGEMs editor-in-chief reviews the EDM Forum's early experiences with open
access publishing. EGEMS TO DATE: As of the end of September 2014 eGEMs has
published 59 manuscripts and received nearly 150 submissions. These early
findings demonstrate eGEMs is filling a need for dissemination outlets that
bridge the gap between the health research and practice communities. Published
papers are distributed across the EDM Forum's four thematic domains: governance
(n=5), informatics (n=14), methods (n=13) and learning health systems (n=27).
While system design issues are a consistent theme, papers addressing priority
health topics such as diabetes, asthma, and obesity are frequently submitted.
Authors include more than two hundred experts in the field representing nearly
all of the EDM Forum's core stakeholder groups: research/QI, nonprofit/policy,
healthcare delivery, government, industry, and patients/consumers. WHAT'S NEXT:
With the help of our diverse community, eGEMs will continue to expand its depth
and reach. Forthcoming special issues on community-level transformation using
health IT, and ways to improve user-experience and system design will add to the
journal's robust portfolio of work identifying and addressing shared challenges
using EHD. The EDM Forum, working closely with our partners at the Agency for
Healthcare Research and Quality, will work diligently to ensure eGEMs is
accelerating the pace at which the community translates and disseminates key
lessons, with the ultimate goal of helping transform knowledge into actions that
can improve health and health care.
PMID- 25848603
TI - The DARTNet Institute: Seeking a Sustainable Support Mechanism for Electronic
Data Enabled Research Networks.
AB - CONTEXT: Clinical data research networks require large investments in
infrastructure support to maintain their abilities to extract, transform, and
load data from varied data sources, expand electronic data sources and develop
learning communities. CASE DESCRIPTION: This paper outlines a sustainable
business model of ongoing infrastructure support for clinical data research
activities. The DARTNet Institute is a not-for-profit 501(c)(3) organization that
serves as a support entity for multiple practice-based research networks. Several
clinical data research networks working closely with a professional society began
collaborating to support shared goals in 2008. This loose affiliation called
itself the "DARTNet Collaborative." In 2011, the DARTNet Institute incorporated
as an independent, not-for-profit entity. The business structure allows DARTNet
to advocate for all partners without operating its own practice-based research
network, serve as a legal voice for activities that overlap multiple partners,
share personnel resources through service contracts between partners, and
purchase low-cost (nonprofit rate) software. MAJOR THEMES: DARTNet's business
model relies upon four diverse sources of revenue: (1) DARTNet licenses and
provides access to a propriety software system that extracts, transforms, and
loads data from all major electronic health records (EHRs) utilized in the United
States, and which also provides clinical decision support for research studies;
(2) DARTNet operates a recognized, national professional-society-quality
improvement registry that enables organizations to fulfill Meaningful Use 2
criteria; (3) DARTNet provides access to data for research activities that are
funded by direct research dollars, provided at prices that generate excess
revenue; and (4) DARTNet provides access to large primary care datasets for
observational studies and pregrant analyses such as for sample size development.
The ability of the system to support pragmatic trials will be described.
CONCLUSION: The DARTNet model facilitates the use of direct grant dollars to
generate revenue to support the overall enterprise through a purchased services
arrangement. Other services provided through subcontracting provide facilities
and administration fees as well as direct dollars to support the system. The
flexibility of the business model overcomes the complicated financial
arrangements and governance requirements of many professional associations and
academic medical centers.
PMID- 25848604
TI - State synergies and disease surveillance: creating an electronic health data
communication model for cancer reporting and comparative effectiveness research
in kentucky.
AB - PURPOSE: This case study describes the collaboration between a state public
health department, a major research university, and a health extension service
funded as part of the Health Information Technology for Economic and Clinical
Health (HITECH) Act to establish an interoperable health information system for
disease surveillance through electronic reporting of systemic therapy data from
numerous oncology practices in Kentucky. The experience of the Kentucky cancer
surveillance system can help local and state entities achieve greater
effectiveness in designing communication efforts to increase usage of electronic
health records (EHRs) and health information exchanges (HIEs), help eligible
clinicians meet these new standards in patient care, and conduct disease
surveillance in a learning health system. INNOVATION: We document and assess the
statewide efforts of early health information technology (HIT) adopters in
Kentucky to facilitate the nation's first electronic transmission of a clinical
document architecture (CDA) from a physician office to a state cancer
surveillance registry in November 2012. Successful transmission of the CDA not
only represented a landmark for technology innovators, informaticists, and
clinicians, but it also set in motion a new communication mechanism by which
state and federal agencies can capture and trade vital cancer statistics in a way
that is safe, secure, and timely. The corresponding impact this has on cancer
surveillance and comparative effective research is immense. With guidance from
the Centers for Disease Control and Prevention (CDC), the Kentucky Cancer
Registry (KCR), the Kentucky Health Information Exchange (KHIE), and the Kentucky
Regional Extension Center (KREC) have moved one step further in transforming the
interoperable health environment for improved disease surveillance. CREDIBILITY:
This case study describes the efforts of established and reputable agencies,
including the KCR, the state department of health, state and federal governmental
agencies, and a major research university in leveraging existing networks,
infrastructure, and federally awarded funding to implement interoperable health
information systems for disease surveillance. Project assessment through quasi
qualitative interviews with key stakeholders facilitated evaluation of attitudes
and beliefs for continued use of the cancer surveillance model. CONCLUSION AND
DISCUSSION: In Kentucky, the cancer reporting initiative leveraged and enhanced a
solid foundation for statewide collaboration to achieve better health and
improved disease surveillance through a learning health system. Leveraging the
Meaningful Use (MU) program as an overarching policy and structural driver is
imperative. The cancer reporting initiative in Kentucky suggests that future
surveillance and reporting initiatives will require locally adaptable solutions
and that there is a need for increased technical assistance in rural settings.
Kentucky's experience also indicates that stakeholders should be diligent in
identifying state-level criteria that align with MU for vetting EHR vendors.
PMID- 25848606
TI - Achieving and sustaining automated health data linkages for learning systems:
barriers and solutions.
AB - INTRODUCTION: Delivering more appropriate, safer, and highly effective health
care is the goal of a learning health care system. The Agency for Healthcare
Research and Quality (AHRQ) funded enhanced registry projects: (1) to create and
analyze valid data for comparative effectiveness research (CER); and (2) to
enhance the ability to monitor and advance clinical quality improvement (QI).
This case report describes barriers and solutions from one state-wide enhanced
registry project. METHODS: The Comparative Effectiveness Research and Translation
Network (CERTAIN) deployed the commercially available Amalga Unified Intelligence
SystemTM (Amalga) as a central data repository to enhance an existing QI registry
(the Automation Project). An eight-step implementation process included hospital
recruitment, technical electronic health record (EHR) review, hospital-specific
interface planning, data ingestion, and validation. Data ownership and security
protocols were established, along with formal methods to separate data management
for QI purposes and research purposes. Sustainability would come from lowered
chart review costs and the hospital's desire to invest in the infrastructure
after trying it. FINDINGS: CERTAIN approached 19 hospitals in Washington State
operating within 12 unaffiliated health care systems for the Automation Project.
Five of the 19 completed all implementation steps. Four hospitals did not
participate due to lack of perceived institutional value. Ten hospitals did not
participate because their information technology (IT) departments were
oversubscribed (e.g., too busy with Meaningful Use upgrades). One organization
representing 22 additional hospitals expressed interest, but was unable to
overcome data governance barriers in time. Questions about data use for QI versus
research were resolved in a widely adopted project framework. Hospitals
restricted data delivery to a subset of patients, introducing substantial
technical challenges. Overcoming challenges of idiosyncratic EHR implementations
required each hospital to devote more IT resources than were predicted. Cost
savings did not meet projections because of the increased IT resource
requirements and a different source of lowered chart review costs. DISCUSSION:
CERTAIN succeeded in recruiting unaffiliated hospitals into the Automation
Project to create an enhanced registry to achieve AHRQ goals. This case report
describes several distinct barriers to central data aggregation for QI and CER
across unaffiliated hospitals: (1) competition for limited on-site IT expertise,
(2) concerns about data use for QI versus research, (3) restrictions on data
automation to a defined subset of patients, and (4) unpredictable resource needs
because of idiosyncrasies among unaffiliated hospitals in how EHR data are coded,
stored, and made available for transmission-even between hospitals using the same
vendor's EHR. Therefore, even a fully optimized automation infrastructure would
still not achieve complete automation. The Automation Project was unable to align
sufficiently with internal hospital objectives, so it could not show a compelling
case for sustainability.
PMID- 25848605
TI - Sustaining Research Networks: the Twenty-Year Experience of the HMO Research
Network.
AB - PURPOSE: As multi-institutional research networks assume a central role in
clinical research, they must address the challenge of sustainability. Despite its
importance, the concept of network sustainability has received little attention
in the literature, and the sustainability strategies of durable scientific
networks have not been described. INNOVATION: The Health Maintenance Organization
Research Network (HMORN) is a consortium of 18 research departments in integrated
health care delivery systems with over 15 million members in the United States
and Israel. The HMORN has coordinated federally funded scientific networks and
studies since 1994. This case study describes the HMORN approach to
sustainability, proposes an operational definition of network sustainability, and
identifies 10 essential elements that can enhance sustainability. CREDIBILITY:
The sustainability framework proposed here is drawn from prior publications on
organizational issues by HMORN investigators and from the experience of recent
HMORN leaders and senior staff. CONCLUSION AND DISCUSSION: Network sustainability
can be defined as (1) the development and enhancement of shared research assets
to facilitate a sequence of research studies in a specific content area or
multiple areas, and (2) a community of researchers and other stakeholders who
reuse and develop those assets. Essential elements needed to develop the shared
assets of a network include: network governance; trustworthy data and processes
for sharing data; shared knowledge about research tools; administrative
efficiency; physical infrastructure; and infrastructure funding. The community of
researchers within a network is enhanced by: a clearly defined mission, vision
and values; protection of human subjects; a culture of collaboration; and strong
relationships with host organizations. While the importance of these elements
varies based on the membership and goals of a network, this framework for
sustainability can enhance strategic planning within the network and can guide
relationships with external stakeholders.
PMID- 25848607
TI - The national anesthesia clinical outcomes registry: a sustainable model for the
information age?
AB - Anesthesiologists care for patients of all ages, with all conceivable
comorbidities, in every kind of health care facility. This leads to a significant
challenge in the collection of data to describe the specialty, and in the
development of evidence-based performance measures for anesthesiologists. Whereas
narrowly defined medical specialties have developed registries based on manual
abstraction of clinical data from the medical record (e.g., cardiac surgery),
this approach would be prohibitively expensive for anesthesiology, and is
unlikely to generate statistically useful data when major adverse outcomes occur
a handful of times in tens of thousands of cases. The American Society of
Anesthesiologists (ASA) addressed this challenge in 2008 by funding a related
organization, the Anesthesia Quality Institute (AQI), to develop the National
Anesthesia Clinical Outcomes Registry (NACOR). The technical development of this
registry and the approach taken to define the specialty of anesthesiology and the
performance of anesthesiologists may serve as a model for other specialty society
efforts.
PMID- 25848608
TI - Mission and Sustainability of Informatics for Integrating Biology and the Bedside
(i2b2).
AB - INTRODUCTION: A visible example of a successfully disseminated research project
in the healthcare space is Informatics for Integrating Biology and the Bedside,
or i2b2. The project serves to provide the software that can allow a researcher
to do direct, self-serve queries against the electronic healthcare data form a
hospital. The goals of these queries are to find cohorts of patients that fit
specific profiles, while providing for patient privacy and discretion. Sustaining
this resource and keeping its direction has always been a challenge, but ever
more so as the ten year National Centers for Biomedical Computing (NCBCs) sunset
their funding. FINDINGS: Building on the i2b2 structures has helped the
dissemination plans for grants leveraging it because it is a disseminated
national resource. While this has not directly increased the support of i2b2
internally, it has increased the ability of institutions to leverage the resource
and generally leads to increased institutional support. DISCUSSION: The
successful development, use, and dissemination i2b2 has been significant in
clinical research and informatics. Its evolution has been from a local research
data infrastructure to one disseminated more broadly than any other product of
the National Centers for Biomedical Computing, and an infrastructure spawning
larger investments than were originally used to create it. Throughout this, there
were two main lessons about the benefits of dissemination: that people have great
creativity in utilizing a resource in different ways and that broader system use
can make the system more robust. One option for long-term sustainability of the
central authority would be to translate the function to an industry partner.
Another option currently being pursued is to create a foundation that would be a
central authority for the project. CONCLUSION: Over the past 10 years, i2b2 has
risen to be an important staple in the toolkit of health care researchers. There
are now over 110 hospitals that use i2b2 for research. This open-source platform
has a community of developers that are continuously enhancing the analytic
capacities of the platform and inventing new functionality. By understanding how
i2b2 has been sustained, we hope that other research infrastructure projects may
better navigate options in making those initiatives sustainable over time.
PMID- 25848609
TI - Sustainability Through Technology Licensing and Commercialization: Lessons
Learned from the TRIAD Project.
AB - Ongoing transformation relative to the funding climate for healthcare research
programs housed in academic and non-profit research organizations has led to a
new (or renewed) emphasis on the pursuit of non-traditional sustainability
models. This need is often particularly acute in the context of data management
and sharing infrastructure that is developed under the auspices of such research
initiatives. One option for achieving sustainability of such data management and
sharing infrastructure is the pursuit of technology licensing and
commercialization, in an effort to establish public-private or equivalent
partnerships that sustain and even expand upon the development and dissemination
of research-oriented data management and sharing technologies. However, the
critical success factors for technology licensing and commercialization efforts
are often unknown to individuals outside of the private sector, thus making this
type of endeavor challenging to investigators in academic and non-profit
settings. In response to such a gap in knowledge, this article will review a
number of generalizable lessons learned from an effort undertaken at The Ohio
State University to commercialize a prototypical research-oriented data
management and sharing infrastructure, known as the Translational Research
Informatics and Data Management (TRIAD) Grid. It is important to note that the
specific emphasis of these lessons learned is on the early stages of moving a
technology from the research setting into a private-sector entity and as such are
particularly relevant to academic investigators interested in pursuing such
activities.
PMID- 25848610
TI - Sustainability considerations for health research and analytic data
infrastructures.
AB - INTRODUCTION: The United States has made recent large investments in creating
data infrastructures to support the important goals of patient-centered outcomes
research (PCOR) and comparative effectiveness research (CER), with still more
investment planned. These initial investments, while critical to the creation of
the infrastructures, are not expected to sustain them much beyond the initial
development. To provide the maximum benefit, the infrastructures need to be
sustained through innovative financing models while providing value to PCOR and
CER researchers. SUSTAINABILITY FACTORS: Based on our experience with creating
flexible sustainability strategies (i.e., strategies that are adaptive to the
different characteristics and opportunities of a resource or infrastructure), we
define specific factors that are important considerations in developing a
sustainability strategy. These factors include assets, expansion, complexity, and
stakeholders. Each factor is described, with examples of how it is applied. These
factors are dimensions of variation in different resources, to which a
sustainability strategy should adapt. SUMMARY OBSERVATIONS: We also identify
specific important considerations for maintaining an infrastructure, so that the
long-term intended benefits can be realized. These observations are presented as
lessons learned, to be applied to other sustainability efforts. We define the
lessons learned, relating them to the defined sustainability factors as
interactions between factors. CONCLUSION AND NEXT STEPS: Using perspectives and
experiences from a diverse group of experts, we define broad characteristics of
sustainability strategies and important observations, which can vary for
different projects. Other descriptions of adaptive, flexible, and successful
models of collaboration between stakeholders and data infrastructures can expand
this framework by identifying other factors for sustainability, and give more
concrete directions on how sustainability can be best achieved.
PMID- 25848611
TI - Sustaining the effective use of health care data: a message from the editors.
AB - INTRODUCTION: Over the past decade, several initiatives have funded large
projects to develop clinical research data infrastructures totaling several
hundred million dollars. While most of this funding has ended or is expected to
end soon, the projects themselves must struggle to continue operations beyond the
initial funding. Examples of sustained research-data infrastructures are lacking,
and recommended approaches to improve sustainability of developing
infrastructures are even rarer. Early on, the Electronic Data Methods (EDM) Forum
and the Agency for Healthcare Research and Quality (AHRQ) as its sponsor
recognized the need to study strategies for sustainability. THEMES: Three
prominent themes relating to sustainability arise among the articles in this
special issue: the importance of project maturity, commercialization activities,
and stakeholder support. Maturity was relevant to all the papers since a
project's maturity directly influences the opportunities that are available,
while commercialization and stakeholder support emerged from comparisons among
subsets of articles. NEXT STEPS: The papers in this issue create a useful initial
set of case studies to help in understanding sustainability issues for data
infrastructures needed for research and QI. Each paper includes important lessons
learned from the authors' experience with the different projects that should
resonate with the broader fields of clinical research and clinical research
informatics. There is an ongoing need for greater understanding of sustainability
beyond what this issue provides. As more case studies of sustainability are
accumulated, it is expected even more important themes will emerge from
qualitative reviews that can eventually be demonstrated quantitatively.
PMID- 25848612
TI - The keys to governance and stakeholder engagement: the southeast michigan beacon
community case study.
AB - Community-based health information exchanges (HIEs) and efforts to consolidate
and house data are growing, given the advent of Accountable Care Organizations
(ACOs) under the Affordable Care Act and other similar population health focused
initiatives. The Southeast Michigan Beacon Community (SEMBC) can be looked to as
one case study that offers lessons learned, insights on challenges faced and
accompanying workarounds related to governance and stakeholder engagement. The
SEMBC case study employs an established Data Warehouse Governance Framework to
identify and explain the necessary governance and stakeholder engagement
components, particularly as they relate to community-wide data sharing and data
warehouses or repositories. Perhaps the biggest lesson learned through the SEMBC
experience is that community-based work is hard. It requires a great deal of
community leadership, collaboration and resources. SEMBC found that
organizational structure and guiding principles needed to be continually
revisited and nurtured in order to build the relationships and trust needed among
stakeholder organizations. SEMBC also found that risks and risk mitigation
tactics presented challenges and opportunities at the outset and through the
duration of the three year pilot period. Other communities across the country
embarking on similar efforts need to consider realistic expectations about
community data sharing infrastructures and the accompanying and necessary
governance and stakeholder engagement fundamentals.
PMID- 25848613
TI - How a Beacon Community Program in New Orleans Helped Create a Better Health Care
System by Building Relationships before Technology.
AB - INTRODUCTION: In the aftermath of Hurricane Katrina, much of New Orleans'
healthcare infrastructure was destroyed. Initial federal funding after the storm
expanded primary care services and helped set up medical homes for New Orleans'
large uninsured and underinsured population. Following that, the Beacon Community
in New Orleans, charged with improving health care through the use of technology,
decided the best way to accomplish those goals was to build community
partnerships and introduce technology improvements based on their input and on
their terms. The purpose of this paper is to describe how those partnerships were
wrought, including the innovative use of a conceptual framework, and how they are
being sustained; how different technologies were and are being introduced; and
what the results have been so far. METHODS: Past successful community
experiences, as well as a proven conceptual framework, were used to help
establish community partnerships and governance structures, as well as to
demonstrate their linkages. This paper represents a compilation of reports and
information from key Beacon leaders, staff and providers and their firsthand
experiences in setting up those structures, as well as their conclusions.
RESULTS: The community partnerships proved extremely successful in not only
devising successful ways to introduce new technology into healthcare settings,
but in sustaining those changes by creating a governance structure that has
enough fluidity to adapt to changing circumstances. CONCLUSIONS: Building and
developing community partnerships takes time and effort; however, these
relationships are necessary and essential to introducing and sustaining new
technologies in a healthcare setting and should be a first step for any
organization looking to accomplish such goals.
PMID- 25848614
TI - How patients can improve the accuracy of their medical records.
AB - OBJECTIVES: Assess (1) if patients can improve their medical records' accuracy if
effectively engaged using a networked Personal Health Record; (2) workflow
efficiency and reliability for receiving and processing patient feedback; and (3)
patient feedback's impact on medical record accuracy. BACKGROUND: Improving
medical record' accuracy and associated challenges have been documented
extensively. Providing patients with useful access to their records through
information technology gives them new opportunities to improve their records'
accuracy and completeness. A new approach supporting online contributions to
their medication lists by patients of Geisinger Health Systems, an online patient
engagement advocate, revealed this can be done successfully. In late 2011,
Geisinger launched an online process for patients to provide electronic feedback
on their medication lists' accuracy before a doctor visit. Patient feedback was
routed to a Geisinger pharmacist, who reviewed it and followed up with the
patient before changing the medication list shared by the patient and the
clinicians. METHODS: The evaluation employed mixed methods and consisted of
patient focus groups (users, nonusers, and partial users of the feedback form),
semi structured interviews with providers and pharmacists, user observations with
patients, and quantitative analysis of patient feedback data and pharmacists'
medication reconciliation logs. FINDINGS/DISCUSSION: (1) Patients were eager to
provide feedback on their medications and saw numerous advantages. Thirty percent
of patient feedback forms (457 of 1,500) were completed and submitted to
Geisinger. Patients requested changes to the shared medication lists in 89
percent of cases (369 of 414 forms). These included frequency-or dosage changes
to existing prescriptions and requests for new medications (prescriptions and
over-the counter). (2) Patients provided useful and accurate online feedback. In
a subsample of 107 forms, pharmacists responded positively to 68 percent of
patient requests for medication list changes. (3) Processing patient feedback
will requires both software algorithms and human interpretation. For the 107
forms subsample, pharmacists accepted patient input in 51 percent of cases where
they could not contact the patient. Where the patient was contacted, they
accepted feedback from 68 percent. This suggests there may be opportunities to
automate feedback filtering and processing for more efficient (and larger scale)
medication-list optimization. (4) A supportive overall e-health environment makes
acceptance of an online patient feedback system more likely. Review of Geisinger
usage data showed patients who completed the medication feedback form had
previously accessed MyGeisinger 2.3 times as often as the average patient and
initiated secure messages with a clinician 1.35 times as often as patients not
involved in the pilot. CONCLUSIONS: Patient feedback, placed in a useful
workflow, can improve medical record accuracy. Electronic health record (EHR)
vendors and developers need to build appropriate capabilities into applications.
Continued research and development is needed for enabling health care
organizations to elicit and process patient information most effectively.
PMID- 25848615
TI - Leveraging health information exchange to improve population health reporting
processes: lessons in using a collaborative-participatory design process.
AB - INTRODUCTION: Surveillance, or the systematic monitoring of disease within a
population, is a cornerstone function of public health. Despite significant
investment in information technologies (IT) to improve the public's health,
health care providers continue to rely on manual, spontaneous reporting processes
that can result in incomplete and delayed surveillance activities. BACKGROUND:
Participatory design principles advocate including real users and stakeholders
when designing an information system to ensure high ecological validity of the
product, incorporate relevance and context into the design, reduce misconceptions
designers can make due to insufficient domain expertise, and ultimately reduce
barriers to adoption of the system. This paper focuses on the collaborative and
informal participatory design process used to develop enhanced, IT-enabled
reporting processes that leverage available electronic health records in a health
information exchange to prepopulate notifiable-conditions report forms used by
public health authorities. METHODS: Over nine months, public health stakeholders,
technical staff, and informatics researchers were engaged in a multiphase
participatory design process that included public health stakeholder focus
groups, investigator-engineering team meetings, public health survey and census
regarding high-priority data elements, and codesign of exploratory prototypes and
final form mock-ups. FINDINGS: A number of state-mandated report fields that are
not highly used or desirable for disease investigation were eliminated, which
allowed engineers to repurpose form space for desired and high-priority data
elements and improve the usability of the forms. Our participatory design process
ensured that IT development was driven by end user expertise and needs, resulting
in significant improvements to the layout and functionality of the reporting
forms. DISCUSSION: In addition to informing report form development, engaging
with public health end users and stakeholders through the participatory design
process provided new insights into public health workflow and allowed the team to
quickly triage user requests while managing user expectations within the realm of
engineering possibilities. CONCLUSION: Engaging public health, engineering staff,
and investigators in a shared codesigning process ensured that the new forms will
not only meet real-life needs but will also support development of a product that
will be adopted and, ultimately, improve communicable and infectious disease
reporting by clinicians to public health.
PMID- 25848616
TI - Developing a communitywide electronic health record disease registry in primary
care practices: lessons learned from the Western new york beacon community.
AB - BACKGROUND AND INTRODUCTION: Disease registries, as part of electronic health
records (EHRs), have shown promise in improving care and outcomes. However,
little is known about how best to implement them across communities, especially
in communities that are not highly integrated. The Western New York (WNY) primary
care community consists largely of independent practices using at least 20
different EHR products. This paper discusses the processes undertaken to develop
a communitywide EHR disease registry in WNY, improvements it engendered, barriers
overcome, and the lessons learned. METHODS: HEALTHeLINK, under the Office of the
National Coordinator for Health Information Technology Beacon Community
Initiative, reached out to 98 primary care practices in the WNY region to
establish EHR-based diabetes registries. Working with practices, community
partners, and vendors, registry specifications were created. The registry was
piloted with practices using one local vendor's EHR product and then rolled out
to other practices, including five other EHR products. Using identified and de
identified registry datasets, quality benchmarking within and between practices
and population health management were undertaken. FINDINGS: From 2011 to 2013,
the WNY Beacon Community assisted 98 practices (344 providers) serving over
50,000 adult diabetic patients. A major focus was on EHR registry development
across diverse systems, and overcoming the challenges this presented. The Beacon
diabetes registry was implemented at 85 of the 98 targeted practices. Of these
registries, 65 met the criteria described in a later section for quality
benchmarking and population health management purposes. Practices received
quarterly benchmark reports summarizing their performance on key diabetes quality
metrics and were compared to community practice averages. Practices used their
registries for population health management by identifying and targeting patients
in need of follow-up or specific diabetes-related care. DISCUSSION AND
CONCLUSION: The creation of the registry infrastructure required unified registry
technical specifications as well as close collaboration between all parties
involved. The WNY experience showed that a useful disease registry can be
established in a community largely consisting of numerous disparate primary care
practices. This laid the groundwork for the future use of EHR data for a variety
of purposes in the community. The methods used and lessons learned through this
endeavor may benefit other communities in a similar position, with several
disconnected EHRs, to establish unified registries.
PMID- 25848618
TI - Creating a connected community: lessons learned from the Western new york beacon
community.
AB - INTRODUCTION: Secure exchange of clinical data among providers has the potential
to improve quality, safety, efficiency, and reduce duplication. Many communities
are experiencing challenges in building effective health information exchanges
(HIEs). Previous studies have focused on financial and technical issues regarding
HIE development. This paper describes the Western New York (WNY) HIE growth and
lessons learned about accelerating progress to become a highly connected
community. METHODS: HEALTHeLINK, with funding from the Office of the National
Coordinator for Health Information Technology (ONC) under the Beacon Community
Program, expanded HIE usage in eight counties. The communitywide transformation
process used three main drivers: (1) a communitywide Electronic Health Record
(EHR) adoption program; (2) clinical transformation partners; and (3) HIE
outreach and infrastructure development. RESULTS: ONC Beacon Community funding
allowed WNY to achieve a new level in the use of interoperable HIE. Electronic
delivery of results into the EHR expanded from 23 practices in 2010 to 222
practices in 2013, a tenfold increase. There were more than 12.5 million results
delivered electronically (HL7 messages) to 222 practices' EHRs via the HIE in
2013. Use of a secure portal and Virtual Health Record (VHR) to access reports
(those not delivered directly to the EHR) also increased significantly, from
13,344 report views in 2010 to over 600,000 in 2013. DISCUSSION AND CONCLUSION:
The WNY Beacon successfully expanded the sharing of clinical information among
different sources of data and providers, creating a highly connected community to
improve the quality and continuity of care. Technical, organizational, and
community lessons described in this paper should prove beneficial to others as
they pursue efforts to create connected communities.
PMID- 25848617
TI - Emphasizing Public Health Within a Health Information Exchange: An Evaluation of
the District of Columbia's Health Information Exchange Program.
AB - INTRODUCTION: Clinovations Government Solutions (CGS) was contracted in 2013 to
conduct a mixed-methods evaluation of the District of Columbia (D.C.) Health
Information Exchange (HIE) program as part of their Cooperative Agreement Grant
funded by the Office of the National Coordinator in 2010. The evaluation was to
focus on the progress of the HIE, how many providers and hospitals were
participating in the program, and what benefits were being realized through the
use of the HIE. During the course of the evaluation, the CGS team found that the
use of the HIE to support public health reporting was one of its core elements.
BACKGROUND: The D.C. HIE is one of 56 HIE that were funded out of the Cooperative
Agreement program. The HIE program was managed by the District of Columbia
Department of Health Care Finance (DHCF), which also manages the District of
Columbia Medicaid Program. The program was initially designed to accomplish the
following: developing state-level directories and enabling technical services for
HIE within and across states; ensuring an effective model for governance and
accountability; coordinating an integrated approach with Medicaid and public
health; and developing or updating privacy and security requirements for HIE
within and across state borders. As the evaluation progressed, the CGS team
discovered that the relationship between the DHCF and the District of Columbia
Department of Health (DOH) had become a cornerstone of the D.C. HIE program.
METHODS: The CGS team used a mixed-methods approach for the evaluation, including
a review of documents developed by the DHCF in its HIE program, including its
original application. We also conducted 10 key informant interviews and moderated
two small-group discussions using a semistructured protocol; and we developed a
survey that measured the use, satisfaction, and future sustainability of the HIE
for over 200 providers within the District of Columbia. FINDINGS: While the
evaluation focused on the D.C. HIE program in its entirety, the results indicated
the value of utilizing the HIE for public health reporting to enhance the
surveillance activities of the DOH. Specifically, the DHCF and DOH collaboration
resulted in using the HIE to electronically capture and report immunization data;
and in requiring electronic lab reporting and results as part of the Meaningful
Use Requirement-which can assist in detecting HIV/AIDS and providing better care
for the district's high population of individuals with HIV/AIDS. Electronic lab
reporting and electronic prescribing within the HIE can assist the DOH and
providers in identifying specific diseases, such as tuberculosis and viral
hepatitis, before they affect a significant part of the population. DISCUSSION:
Given the severe health disparities in the district, the ability of the D.C. HIE
program to collect public health information on affected populations will be
instrumental in better understanding and identifying methods of supporting these
populations through improved surveillance and identification of the appropriate
treatments. The D.C. HIE program is uniquely positioned to support these
populations due to the partnership of DHCF with the D.C. DOH. CONCLUSION AND NEXT
STEPS: The District of Columbia has made significant strides in expanding its
public health infrastructure and activities. Three key areas of growth were
identified that have the potential to transform the District of Columbia's public
health approach: establishing sufficient feedback loops, collection of
environmental data, integration, and interoperability.
PMID- 25848619
TI - Building and strengthening infrastructure for data exchange: lessons from the
beacon communities.
AB - INTRODUCTION: The Beacon Community Cooperative Agreement Program supports
interventions, including care-delivery innovations, provider performance
measurement and feedback initiatives, and tools for providers and consumers to
enhance care. Using a learning health system framework, we examine the Beacon
Communities' processes in building and strengthening health IT (HIT)
infrastructures, specifically successes and challenges in sharing patient
information to improve clinical care. BACKGROUND: In 2010, the Office of the
National Coordinator for Health Information Technology (ONC) launched the three
year program, which provided $250 million to 17 Beacon Communities to invest in
HIT and health information exchange (HIE) infrastructure. Beacon Communities used
this funding to develop and disseminate HIT-enabled quality improvement practices
found effective in particular community and practice environments. METHODS: NORC
conducted 7 site visits, November 2012-March 2013, selecting Communities to
represent diverse program features. From August-October 2013, NORC held
discussions with the remaining 10 Communities. Following each visit or
discussion, NORC summarized the information gathered, including transcripts, team
observations, and other documents the Community provided, to facilitate a within
Community analysis of context and stakeholders, intervention strategies, enabling
factors, and challenges. RESULTS: Although each Community designed and
implemented data-sharing strategies in a unique environment, similar challenges
and enabling factors emerged across the Beacons. From a learning health system
perspective, their strategies to build and strengthen data-sharing
infrastructures address the following crosscutting priorities: promoting
technical advances and innovations by helping providers adapt EHRs for data
exchange and performance measurement with customizable IT and offering technical
support to smaller, independent providers; engaging key stakeholders; and
fostering transparent governance and stewardship of the infrastructure with
neutral conveners. CONCLUSION: While all the Communities developed or
strengthened data-exchange infrastructure, each did this in a unique environment
of existing health care market and legal factors. The Communities, however,
encountered similar challenges and enabling factors. Organizations undertaking
collaborative data sharing, performance measurement and clinical transformation
can learn from the Beacon Communities' experience.
PMID- 25848620
TI - Beacon communities' public health initiatives: a case study analysis.
AB - INTRODUCTION: The Beacon Communities for Public Health (BCPH) project was
launched in 2011 to gain a better understanding of the range of activities
currently being conducted in population- and public health by the Beacon
Communities. The project highlighted the successes and challenges of these
efforts with the aim of sharing this information broadly among the public health
community. BACKGROUND: The Beacon Community Program, designed to showcase
technology-enabled, community-based initiatives to improve outcomes, focused on:
building and strengthening health information technology (IT) infrastructure and
exchange capabilities; translating investments in health IT to measureable
improvements in cost, quality, and population health; and, developing innovative
approaches to performance measurement, technology, and care delivery. METHODS:
Four multimethod case studies were conducted based on a modified sociotechnical
framework to learn more about public health initiative implementation and use in
the Beacon Communities. Our methodological approach included using document
review and semistructured key informant interviews. NACCHO Model Practice Program
criteria were used to select the public health initiatives included in the case
studies. FINDINGS: Despite differences among the case studies, common barriers
and facilitators were found to be present in all areas of the sociotechnical
framework application including structure, people, technology, tasks, overarching
considerations, and sustainability. Overall, there were many more facilitators
(range = 7-14) present for each Beacon compared to barriers (range = 4-6).
DISCUSSION: Four influential promising practices were identified through the
work: forging strong and sustainable partnerships; ensuring a good task
technology fit and a flexible and iterative design; fostering technology
acceptance; and, providing education and demonstrating value. CONCLUSIONS: A
common weakness was the lack of a framework or model for the Beacon Communities
evaluation work. Sharing a framework or approach to evaluation at the beginning
of implementation made the work more effective. Supporting evaluation to inform
future implementations is important.
PMID- 25848621
TI - Supporting primary care practices in building capacity to use health information
data.
AB - INTRODUCTION: Our objective was to describe essential support resources and
strategies in order to advance the pace and scope of the use of health
information technology (HIT) data. BACKGROUND AND CONTEXT: Primary data were
collected between January 2011 and October 2012. The primary study population
comprised 51 primary care practices enrolled in the Colorado Beacon Consortium in
western Colorado. METHODS: We used qualitative methods embedded in a mixed-method
evaluation: monthly narrative reports from practices; interviews with providers
and staff; and focused, group discussions with quality improvement (QI) advisors
and staff from the Health Information Technology Regional Extension Center.
FINDINGS: Practices valued effective support strategies to assist with using HIT,
including the following: translating rules and regulations into individual
practice settings; facilitating peer-to-peer connections; providing processes and
tools for practice improvement; maintaining accountability and momentum; and
providing local electronic health record (EHR) technical expertise. Benefits of
support included improved quality measures, operational improvements, increased
provider and staff engagement, and deeper understanding of EHR data. DISCUSSION:
The findings affirm the utility of practice facilitation for HIT-focused aims
with personalized attention and cross-fertilization among practices for
improvements. Facilitation to sustain ongoing improvements and prepare for future
HIT-intensive improvement activities was highly valued. In addition to the
general practice facilitator, an EHR technical expert was critical to improving
practice capacity to use electronic clinical data. Collaborative learning expands
the pool of mentors and teachers, who can further translate their own lessons
into practical advice for their peers, yielding the emergence of a stronger sense
of community among the practices. CONCLUSIONS: Using HIT more effectively in
primary care will require sustained, focused efforts by practices as regulations,
incentives and HIT evolve. Ongoing support for community-based practice
facilitators; collaborative learning; and local, personalized EHR advisors will
help practices care for patients while more effectively deploying HIT to improve
care.
PMID- 25848622
TI - Enhancing a geriatric emergency department care coordination intervention using
automated health information exchange-based clinical event notifications.
AB - PURPOSE: In a health care system where patients often have numerous providers and
multiple chronic medical conditions, interoperability of health information
technology (HIT) is of paramount importance. Regional health information
organizations (RHIO) often provide a health information exchange (HIE) as a
solution, which gives stakeholders access to clinical data that they otherwise
would not otherwise have. A secondary use of preexisting HIE infrastructure is
clinical event notification (CEN) services, which send automated notifications to
stakeholders. This paper describes the development and implementation of a CEN
service enabled by a RHIO in the New York metropolitan area to improve care
coordination for patients enrolled in a geriatric emergency department care
coordination program. INNOVATION: This operational CEN system incorporates
several innovations that to our knowledge have not been implemented previously.
They include the near real-time notifications and the delivery of notifications
via multiple pathways: electronic health record (EHR) "in-baskets," email, text
message to internet protocol-based "zone" phones, and automated encounter entry
into the EHR. Based on these alerts the geriatric care coordination team contacts
the facility where the patient is being seen and offers additional information or
assistance with disposition planning with the goal of decreasing potentially
avoidable admissions and duplicate testing. FINDINGS: During the nearly one-year
study period, the CEN program enrolled 5722 patients and sent 497 unique
notifications regarding 206 patients. Of these notifications, 219 (44%) were for
emergency department (ED) visits; 121 (55%) of those notifications were received
during normal business hours when the care coordination team was available to
contact the ED where the patient was receiving care. Hospital admissions resulted
from 45% of ED visits 17.8% of these admissions lasted 48 hours or less,
suggesting some might potentially be avoidable. CONCLUSIONS AND DISCUSSION: This
study demonstrates the potential of CEN systems to improve care coordination by
notifying providers of the occurrence of specific events. Although it could not
directly be demonstrated here, we believe that widespread use of CEN systems have
potential to reduce potentially avoidable admissions and duplicate testing,
likely leading to decreased costs.
PMID- 25848623
TI - The Community Health Applied Research Network (CHARN) Data Warehouse: a Resource
for Patient-Centered Outcomes Research and Quality Improvement in Underserved,
Safety Net Populations.
AB - BACKGROUND: The Community Health Applied Research Network, funded by the Health
Resources and Services Administration, is a research network comprising 18
Community Health Centers organized into four Research Nodes (each including an
academic partner) and a data coordinating center. The network represents more
than 500,000 diverse safety net patients across 11 states. OBJECTIVE: The primary
objective of this paper is to describe the development and implementation process
of the CHARN data warehouse. METHODS: The methods involved regulatory and
governance development and approval, development of content and structure of the
warehouse and processes for extracting the data locally, performing validation,
and finally submitting data to the data coordinating center. PROGRESS TO DATE:
Version 1 of the warehouse has been developed. Tables have been added, the
population and the years of electronic health records (EHR) have been expanded
for Version 2. CONCLUSIONS: It is feasible to create a national, centralized data
warehouse with multiple Community Health Center partners using different EHR
systems. It is essential to allow sufficient time: (1) to develop collaborative,
trusting relationships among new partners with varied technology, backgrounds,
expertise, and interests; (2) to complete institutional, business, and regulatory
review processes; (3) to identify and address technical challenges associated
with diverse data environments, practices, and resources; and (4) to provide
continuing data quality assessments to ensure data accuracy.
PMID- 25848624
TI - The utah beacon experience: integrating quality improvement, health information
technology, and practice facilitation to improve diabetes outcomes in small
health care facilities.
AB - PURPOSE: The Utah Improving Care through Connectivity and Collaboration (IC3)
Beacon community (2010-2013) was spearheaded by HealthInsight, a nonprofit,
community-based organization. One of the main objectives of IC(3) was to improve
health care provided to patients with diabetes in three Utah counties,
collaborating with 21 independent smaller clinics and two large health care
enterprises. This paper will focus on the use of health information technology
(HIT) and practice facilitation to develop and implement new care processes to
improve clinic workflow and ultimately improve patients' diabetes outcomes at 21
participating smaller, independent clinics. INNOVATION: Early in the project, we
learned that most of the 21 clinics did not have the resources needed to
successfully implement quality improvement (QI) initiatives. IC(3) helped clinics
effectively use data generated from their electronic health records (EHRs) to
design and implement interventions to improve patients' diabetes outcomes. This
close coupling of HIT, expert practice facilitation, and Learning Collaboratives
was found to be especially valuable in clinics with limited resources. FINDINGS:
Through this process we learned that (1) an extensive readiness assessment
improved clinic retention, (2) clinic champions were important for a successful
collaboration, and (3) current EHR systems have limited functionality to assist
in QI initiatives. In general, smaller, independent clinics lack knowledge and
experience with QI and have limited HIT experience to improve patient care using
electronic clinical data. Additionally, future projects like IC(3) Beacon will be
instrumental in changing clinic culture so that QI is integrated into routine
workflow. CONCLUSION AND DISCUSSION: Our efforts led to significant changes in
how practice staff optimized their EHRs to manage and improve diabetes care,
while establishing the framework for sustainability. Some of the IC(3) Beacon
practices are currently smoothly transitioning to new models of care such as
Patient-Centered Medical Homes. Thus, IC(3) Beacon has been instrumental in
creating a strong community partnership among various organizations to meet the
shared vision of better health and lower costs, and the experience over the last
few years has helped the community prepare for the changing health care
landscape.
PMID- 25848625
TI - The Southeastern Minnesota Beacon Project for Community-driven Health Information
Technology: Origins, Achievements, and Legacy.
AB - INTRODUCTION: The Southeastern (SE) Minnesota Beacon organized all the health
care providers, county public health organizations, and school districts in the
deployment and integration of health information exchange (HIE) and targeted
health communication around childhood asthma and diabetes. The community
cooperated to establish a clinical data repository for all residents in the 11
county region. Through this community of practice approach that involved
traditional and nontraditional providers, the SE Minnesota Beacon was able to
realize unique applications of this technology. This manuscript overviews the
associated organization and infrastructure of this community collaboration.
BACKGROUND: The Office of the National Coordinator for Health Information
Technology (ONC), as part of the American Recovery and Reinvestment Act of 2009
(ARRA) stimulus, established 17 projects throughout the United States targeting
the introduction and meaningful use of health information technology (HIT). These
17 communities were intended to serve as an example of what could be
accomplished. The SE Minnesota Beacon is one of these communities. METHODS: The
community ultimately opted for peer-to-peer HIE, using Nationwide Health
Information Network (NwHIN) Connect software. The clinical data repository was
established using the infrastructure developed by the Regenstrief Institute,
which operated as a trusted third party. As an extension to HIE, the consortium
of county public health departments created a patient data portal for use by
school nurses and parents. Childhood asthma was addressed by creating,
exchanging, and maintaining an "asthma action plan" for each affected child,
shared throughout the community, including through the patient portal. Diabetes
management introduced patient treatment decision tools and patient quality of
life measures, facilitating care. Influenza vaccination was enhanced by large
scale community reporting in partnership with the state vaccination registry. The
methodology and principles for arriving at these solutions included community
engagement, sustainability, scalability, standards, and best practices that fit a
variety of organizations-from large, robust providers to small organizations.
FINDINGS: The SE Minnesota Beacon demonstrated that all providers for a
geographically defined population can cooperate in the development and shared
governance of a low-cost, sustainable HIE, and the operation of a community
managed clinical data repository. Furthermore, these infrastructures can be
leveraged to collaboratively improve the care of patients, as demonstrated for
childhood asthma and adult diabetes mellitus. CONCLUSION: The shared governance
of HIT by a community can palpably change the scope and success of collaborations
targeted to improve patient and community health care.
PMID- 25848626
TI - Evaluating the Reliability of EHR-Generated Clinical Outcomes Reports: A Case
Study.
AB - INTRODUCTION: Quality incentive programs, such as Meaningful Use, operate under
the assumption that clinical quality measures can be reliably extracted from
EHRs. Safety Net providers, particularly Federally Qualified Health Centers and
Look-Alikes, tend to be high adopters of EHRs; however, recent reports have shown
that only about 9% of FQHCs and Look-Alikes were demonstrating meaningful use as
of 2013. Our experience working with the Crescent City Beacon Community (CCBC)
found that many health centers relied on chart audits to report quality measures
as opposed to electronically generating reports directly from their EHRs due to
distrust in the data. This paper describes a step-by-step process for improving
the reliability of data extracted from EHRs to increase reliability of quality
measure reports, to support quality improvement, and to achieve alignment with
national clinical quality reporting requirements. BACKGROUND: Lack of
standardization in data capture and reporting within EHRs drives distrust in EHR
reported data. Practices or communities attempting to achieve standardization may
look to CCBC's experience for guidance on where to start and the level of
resources required in order to execute a data standardization project. During the
time of this data standardization project, CCBC was launching an HIE. Lack of
trust in EHR data was a driver for distrust in the HIE data. METHODS: We present
a case study where a five-step process was used to harmonize measures, reduce
data errors, and increase trust in EHR clinical outcomes reports among a
community of Safety Net providers using a common EHR. Primary outcomes were the
incidence of reporting errors and the potential effect of error types on quality
measure percentages. The activities and level of resources required to achieve
these results were also documented by the CCBC program. FINDINGS: Implementation
of a community-wide data reporting project resulted in measure harmonization,
reduced reporting burden, and error reduction in EHR-generated clinical outcomes
reporting across participating clinics over a nine-month period. Increased
accuracy of clinical outcomes reports provided physicians and clinical care teams
with better information to guide their decision-making around quality improvement
planning. DISCUSSION: A number of challenges exist to achieving reliable
population level quality reporting from EHRs at the practice, vendor, and
community levels. Our experience demonstrates that quality measure reporting from
EHRs is not a straightforward process, and it requires time and close
collaboration between clinics and vendors to improve reliability of reports. Our
experience found that practices valued the opportunity and step-wise process to
validate their data locally (out of their EHRs) prior to reporting out of the
HIE. CONCLUSION AND NEXT STEPS: Communities can achieve higher levels of
confidence in quality measure reporting at the population level by establishing
collaborative user groups that work with EHR vendors as partners and use
technical assistance to build relationships and trust in EHR-generated reports.
While this paper describes the first phase of our work around improving
standardization and reliability of EHR reports, vendors should continue to
explore modifications for improving data capture (at the front-end) via
standardized data entry templates.
PMID- 25848627
TI - IT-enabled Community Health Interventions: Challenges, Opportunities, and Future
Directions.
AB - Rising health information technology (HIT) adoption and the increasing
interoperability of health data have propelled the role of IT in community-wide
health transformations. Disseminating the challenges and opportunities that the
early adopters of community-wide HIT interventions have experienced is critical
for empowering the growing demand for community-based health systems. This
special issue of eGEMs addresses that need. This issue includes a variety of
community-based HIT projects covering topics such as governance, informatics, and
learning health systems. These projects represent a diverse set of stakeholders,
a wide selection of data sources, and multiple information platforms to collate
or exchange data. We hope that this special issue of eGEMs will be the first of
several future issues dedicated to community-wide HIT transformations.
PMID- 25848628
TI - Defining information needs for public health systems and services research.
AB - BACKGROUND: People who lead or manage public health agencies have multiple needs
for information in order to do their jobs effectively. In seeking to investigate
"what works" in public health practice, investigators in the field of public
health systems and services research (PHSSR) have largely overlapping information
needs but often require a greater detail, specificity, or comprehensiveness than
is routinely available in public health data systems. PHSSR DATA NEEDS MEETING:
On April 24, 2014, the PHSSR Center of the University of Kentucky and
AcademyHealth convened a 1-day meeting of public health practitioners and PHSSR
investigators to identify PHSSR information needs. Meeting participants
considered data needs for three PHSSR domains: the organization of public health
agencies and services, the use of rapidly evolving health information
technologies, and the financing and economic evaluation of public health
activities. FUTURE DATA NEEDS: Identifying data needs in these and other PHSSR
domains requires clarification of research questions, consideration of research
methods, a balance of imagination and practicality, and investments to extend the
information captured in existing administrative, financial, and population health
monitoring systems.
PMID- 25848629
TI - Linking costs to health outcomes for allocating scarce public health resources.
AB - INTRODUCTION: Resources for public health (PH) are scarce and policymakers face
tough decisions in determining their funding priorities. The difficulty of making
these decisions is compounded by current PH accounting systems, which are ill
equipped to link fiscal resources to PH outcomes. This paper examines the types
of revenues and expenditures, health services, and health outcomes that are being
tracked at the local and state PH levels. The authors provide recommendations for
strengthening the ability of local and state governments to link expenditures to
PH outcomes, both within and across jurisdictions. FRAMEWORK AND NEXT STEPS: The
source of revenue data for most local jurisdictions is the accounting systems
used for the budgeting and auditing of fiscal activities, and these are primarily
linked to specific PH programs. In contrast, expenditure data are mostly generic
and typically span multiple PH programs with no link to specific PH activities.
Many challenges exist to then link PH activities to health outcomes data, which
are often collected through separate reporting systems at the local, state, and
national levels. Policy change at the state level and implementation strategies
that are standardized across local health departments are required to assess the
costs and health outcomes of PH activities. CONCLUSION: Information linking PH
expenditures to health outcomes of PH services could greatly inform the decision
making process. This information will allow investments in PH to be better
understood and will provide a strong foundation for the PH services and systems
research community to understand variation and drive improvement. Ultimately,
these data could be used to improve accountability at the local and state PH
department levels.
PMID- 25848630
TI - The future of public health informatics: alternative scenarios and recommended
strategies.
AB - BACKGROUND: In October 2013, the Public Health Informatics Institute (PHII) and
Institute for Alternative Futures (IAF) convened a multidisciplinary group of
experts to evaluate forces shaping public health informatics (PHI) in the United
States, with the aim of identifying upcoming challenges and opportunities. The
PHI workshop was funded by the Robert Wood Johnson Foundation as part of its
larger strategic planning process for public health and primary care. WORKSHOP
CONTEXT: During the two-day workshop, nine experts from the public and private
sectors analyzed and discussed the implications of four scenarios regarding the
United States economy, health care system, information technology (IT) sector,
and their potential impacts on public health in the next 10 years, by 2023.
Workshop participants considered the potential role of the public health sector
in addressing population health challenges in each scenario, and then identified
specific informatics goals and strategies needed for the sector to succeed in
this role. RECOMMENDATIONS AND CONCLUSION: Participants developed recommendations
for the public health informatics field and for public health overall in the
coming decade. These included the need to rely more heavily on intersectoral
collaborations across public and private sectors, to improve data infrastructure
and workforce capacity at all levels of the public health enterprise, to expand
the evidence base regarding effectiveness of informatics-based public health
initiatives, and to communicate strategically with elected officials and other
key stakeholders regarding the potential for informatics-based solutions to have
an impact on population health.
PMID- 25848631
TI - Community health needs assessments: filling data gaps for population health
research and management.
AB - INTRODUCTION: Community health needs assessments (CHNA) are completed to meet
varied regulatory and statutory requirements for local public health departments,
tax-exempt 501(c)(3) hospitals, and Federally Qualified Health Centers. Although
compliance is a motivating factor, these entities are committed to understanding
the communities they serve and to developing strategies to address health needs
and inequities in health and health care. FILLING DATA GAPS: CHNAs have the
potential to improve the health of communities and populations by giving crucial
qualitative and quantitative context to hospital and patient data, thereby
enhancing opportunities for health services and clinical outcomes researchers.
Filling in these data gaps can help to improve population health by highlighting
community-and social determinant-related dynamics relevant to the improved health
of the community. CHNAS AND EHRS FOR POPULATION HEALTH: Successful models exist
that that have used CHNAs and the resulting data to improve population health
management and reduce inequities, as do health systems that have used the EHR and
community-based performance measurement data to achieve population health goals.
PMID- 25848632
TI - Development and Implementation of ExPLORE Clinical Practice, a Web-accessible
Comparative Outcomes Tool for California Hospitals and Physicians.
AB - BACKGROUND: Hospital-based clinicians have little information about the outcomes
of their care, much less how those outcomes compare with those of their peers. A
variety of care quality indicators have been developed, but comparisons tend to
be hospitalwide, and often irrelevant to the practice and patient group of many
hospital clinicians. Moreover, information is not enough to transform clinical
practice, as the human response to such comparisons is, "I'm doing the best I
know how." What is needed is granular, clinically specific feedback with peer
mediated advice about how "positive deviants" achieve better results. OBJECTIVE:
This case study reports on the development and implementation of a web-accessible
comparative outcomes tool, ExPLORE Clinical Practice, for hospitals and
clinicians in California. METHODS: We use iterative development and refinement of
web tools to report comparative outcomes; incremental development of suites of
procedure-patient outcome pairs specific to particular medical specialty groups;
testing and refinement of response time metrics to reduce delays in report
generation; and introduction of a comments section for each measure that assists
with interpretation and ties results to strategies found to lead to better
clinical outcomes. RESULTS: To date, 76 reports, each with 115 to 251
statistically evaluated outcomes, are available electronically to compare
individual hospitals in California to statewide outcomes. DISCUSSION AND
CONCLUSIONS: ExPLORE Clinical Practice is one of a number of emerging systems
that attempt to lever available data to improve patient outcomes. The ExPLORE
Clinical Practice system combines a clinical focus on highly specific outcome
measures with attention to technical issues such as crafting an intuitive user
interface and graphic presentation. This case study illustrates the important
advances made in using data to support clinicians to improve care for patients.
We see this information as a way to start local conversations about quality
improvement, and as a means of generating peer advice for improving patient
outcomes.
PMID- 25848633
TI - Adapting practice-based intervention research to electronic environments:
opportunities and complexities at two institutions.
AB - BACKGROUND AND PURPOSE: Primary care practice-based research has become more
complex with increased use of electronic health records (EHRs). Little has been
reported about changes in study planning and execution that are required as
practices change from paper-based to electronic-based environments. We describe
the evolution of a pediatric practice-based intervention study as it was adapted
for use in the electronic environment, to enable other practice-based researchers
to plan efficient, effective studies. METHODS: We adapted a paper-based pediatric
office-level intervention to enhance parent-provider communication about
subspecialty referrals for use in two practice-based research networks (PBRNs)
with partially and fully electronic environments. We documented the process of
adaptation and its effect on study feasibility and efficiency, resource use, and
administrative and regulatory complexities, as the study was implemented in the
two networks. RESULTS: Considerable time and money was required to adapt the
paper-based study to the electronic environment, requiring extra meetings with
institutional EHR-, regulatory-, and administrative teams, and increased practice
training. Institutional unfamiliarity with using EHRs in practice-based research,
and the consequent need to develop new policies, were major contributors to
delays. Adapting intervention tools to the EHR and minimizing practice
disruptions was challenging, but resulted in several efficiencies as compared
with a paper-based project. In particular, recruitment and tracking of subjects
and data collection were easier and more efficient. CONCLUSIONS: Practice-based
intervention research in an electronic environment adds considerable cost and
time at the outset of a study, especially for centers unfamiliar with such
research. Efficiencies generated have the potential of easing the work of study
enrollment, subject tracking, and data collection.
PMID- 25848634
TI - Style Guide: An Interdisciplinary Communication Tool to Support the Process of
Generating Tailored Infographics From Electronic Health Data Using EnTICE3.
AB - PURPOSE: In this case study we describe key features of the structured
communication tool-a style guide-used to support interdisciplinary collaboration,
and we propose the use of such a tool for research teams engaged in similar
projects. We employ tailored infographics to present patient reported outcome
data from a community health survey back, in a comprehensible and actionable
manner, to the individuals who provided it. The style guide was developed to
bridge the semantic gap between the domain and programming experts engaged in
this effort. INNOVATION: The style guide supports the communication of complex
design specifications in a highly structured format that is nevertheless flexible
enough to accommodate project growth. Unlike the typical corporate style guide
that has a more narrative format, our style guide is innovative in its use of
consistent fields across multiple, standalone entries. CREDIBILITY: The process
of populating the style guide prompted the designer toward greater design
efficiency and led to consistent and specific instructions that met the framework
architect's stated information needs. DISCUSSION AND CONCLUSION: The guiding
values in the creation of the style guide were consistency, clarity, and
flexibility. It serves as a durable reference to the desired look and
functionality of the final infographic product without dictating an
implementation strategy. The style guide format can be adapted to meet the
communication needs of other interdisciplinary teams facing a semantic gap.
PMID- 25848635
TI - Quality measure performance in small practices before and after electronic health
record adoption.
AB - INTRODUCTION: To date, little research has been published on the impact that the
transition from paper-based record keeping to the use of electronic health
records (EHR) has on performance on clinical quality measures. This study
examines whether small, independent medical practices improved in their
performance on nine clinical quality measures soon after adopting EHRs. METHODS:
Data abstracted by manual review of paper and electronic charts for 6,007
patients across 35 small, primary care practices were used to calculate rates of
nine clinical quality measures two years before and up to two years after EHR
adoption. RESULTS: For seven measures, population-level performance rates did not
change before EHR adoption. Rates of antithrombotic therapy and smoking status
recorded increased soon after EHR adoption; increases in blood pressure control
occurred later. Rates of hemoglobin A1c testing, BMI recorded, and cholesterol
testing decreased before rebounding; smoking cessation intervention, hemoglobin
A1c control and cholesterol control did not significantly change. DISCUSSION: The
effect of EHR adoption on performance on clinical quality measures is mixed. To
improve performance, practices may need to develop new workflows and adapt to
different documentation methods after EHR adoption. CONCLUSIONS: In the short
term, EHRs may facilitate documentation of information needed for improving the
delivery of clinical preventive services. Policies and incentive programs
intended to drive improvement should include in their timelines consideration of
the complexity of clinical tasks and documentation needed to capture performance
on measures when developing timelines, and should also include assistance with
workflow redesign to fully integrate EHRs into medical practice.
PMID- 25848636
TI - Recruiting for Acute Myocardial Infarction Cell Therapy Trials: Challenges and
Best Practices for the CCTRN.
PMID- 25848637
TI - Morphological methods to evaluate protective agents against aminoglycoside
induced nephrotoxicity.
PMID- 25848638
TI - Important statistical points to improve and promote the methodology of the
articles on medical sciences, particularly nephrology and kidney; a review
article.
AB - BACKGROUND: Quality of articles' methodology is one of the important factors
which is considered by researchers. OBJECTIVES: This study was conducted to
determine statistical guidelines on promotion of methodology's quality in the
articles concerning medical sciences, particularly nephrology, to assist authors
and reviewers. MATERIALS AND METHODS: This study is a systematic review.
Initially, the keywords "Epidemiologic Methods/analysis" [Mesh] OR "Epidemiologic
Methods/epidemiology" and "reporting" were selected in Medline database. Then,
reliable databases were searched for relevant publications. Being relevant,
containing viewpoints, and recommending statistical guidelines as well as
approval of at least two of the three examiners of articles were determined as
the inclusion criteria into the study. RESULTS: Two hundred relevant articles
were retrieved. Thirty-two articles met the inclusion criteria. By the examined
articles, 30 applied points have determinative role for improving and promoting
quality of articles methodology. Of the important points, introducing and
describing target community and statistical population, mentioning article title,
introducing independent and dependent variables as well as confounders, reporting
sample size for subgroups and the whole study, summarizing the data according to
their statistical distribution (reporting mean and standard deviation for data
with normal distribution), reporting the type of rate (incidence, survival),
ratio (odds, hazard) or risk (absolute, relative, difference) with 95% CI and the
used software could be mentioned. CONCLUSION: The most important factors
contributing greatly to the quality of articles' methodology on nephrology were
reported in the present study. Applying these factors by articles authors and
reviewers could lead to improve articles' and journals' quality. In addition, use
of the findings of the present study in articles' materials and methods could
avoid research errors.
PMID- 25848639
TI - Perieccrine and pericapillary calcification in calciphylaxis.
PMID- 25848640
TI - Assessing of the relationship between renal function tests and retinopathy stage
in patients with type II diabetes.
AB - INTRODUCTION: Retinopathy and nephropathy are long-term diabetes complications
which are associated together. Renal dysfunction is a risk factor for progression
and deterioration of diabetic retinopathy. Diabetes causes damage to the small
blood vessels in the retina and kidney which eventually resulted in diabetic
nephropathy, renal failure and blindness. Due to the high cost for treating of
these complications it is better to prevent them. OBJECTIVES: We aimed to assess
the patients' kidney function and retinal status in a group of diabetic patients
to find probable association between nephropathy and retinopathy hence can
prevent from serious renal complications. PATIENTS AND METHODS: In this cross
sectional study 253 patients with type 2 diabetes referring to ophthalmology
clinics were evaluated. Eye examination was conducted by an ophthalmologist
(vitreoretinal subspecialist) and disease stage was determined, then serum blood
urea nitrogen (BUN) and creatinine tests and 24-hour urine collection for
microalbuminuria were measured. RESULTS: Mean of BUN and microalbuminuria had
significant difference in three groups including proliferative retinopathy, non
proliferative retinopathy and patients without retinopathy. The mean (+/- SD) of
serum creatinine in patients with proliferative retinopathy, non-proliferative
retinopathy and patients without retinopathy had no significant difference.
CONCLUSION: The presence or absence of retinopathy in the early stages of
diabetic kidney disease has not related to renal involvement, in fact, patients
without retinopathy may have renal involvement. In periodic examination, diabetic
patients should be evaluated for microalbuminuria in addition to renal function
test examination.
PMID- 25848641
TI - Effect of metabolic syndrome and its components on survival in colorectal cancer:
a prospective study.
AB - INTRODUCTION: Metabolic syndrome (MetS) may affect prognosis of the patients
diagnosed with colorectal cancer (CRC). OBJECTIVES: This study was aimed to
design a model and to examine the prognostic effect of MetS on survival time in
the patients with CRC. PATIENTS AND METHODS: Data were collected from 1127 cases
of CRC from Cancer Registry Center of the Research Institute of Gastroenterology
and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
In this cohort study, patients were divided into two groups based on the presence
of MetS. We tested the prognostic value of MetS in the patients by Cox
proportional hazard modeling. RESULTS: Mean +/- standard deviation of the
patients' age at diagnosis in MetS group and non-MetS group was 56 +/- 13 years
old and 53 +/- 15 years old respectively. Tumor stage as an independent variable
affected CRC survival. The mean survival time of the MetS and non-MetS groups was
23 and 27 months respectively. Independent variables like tumor stage (hazard
ratio [HR], 1.76; 95% CI, 0.29-0.90) and educational level (HR, 0.50; 95% CI,
0.23-0.97) had significant effect on CRC survival and MetS (HR, 0.95; 95% CI,
0.52-1.5), tumor size (HR, 1.390; 95% CI, 1.237-1.560), family history, age,
gender, and smoking had non-significant effect on CRC survival. CONCLUSION: MetS
could be a prognostic factor for survival in the patients with CRC. The results
suggested that effect of MetS was not significant.
PMID- 25848642
TI - A facile synthesis of fluorescent silver nanoclusters with human ferritin as a
synthetic and interfacing ligand.
AB - Water-soluble fluorescent silver nanoclusters (NCs) formed on biomolecule ligands
have been extensively studied due to their great potential as new biocompatible
fluorescent materials for biosensors. As synthetic ligands, proteins in
particular can provide unique structures and functions to the assembled
fluorescent silver clusters. A key challenge, however, is to develop appropriate
protein ligands and synthetic approaches for cluster formation, especially using
native aqueous solutions, to fully preserve the valuable properties of the
protein templates. Here we report a human ferritin-templated synthesis of
fluorescent silver NCs under neutral aqueous buffer conditions. The unique metal
binding property of ferritin and an optimized silver ion reduction allowed us to
produce highly stable fluorescent silver NCs that are steadily assembled in the
cage-like ferritin proteins. The fluorescent clusters were also successfully
assembled on genetically engineered ferritin with antibody-binding protein G. The
resulting protein G-ferritin-silver NC complex fully retained the ferritin
structure as well as the antibody binding ability. The present silver
nanoclusters on ferritin (Ft-Ag NCs) also showed highly specific Cu(2+)-induced
fluorescence quenching. By exploiting the large but stable nature of ferritin, we
fabricated a highly robust and porous hydrogel sensor system for rapid Cu(2+)
detection, where the Ft-Ag NCs were stably encapsulated in surface-bound
hydrogels with large pore sizes. Our Ft-Ag NCs that are formed under native
aqueous conditions will have great potential as a new fluorescent material with
the high structural and functional diversities of ferritin.
PMID- 25848643
TI - An artificial receptor synthesized by surface-confined imprinting for the
recognition of acetylation on histone H4 K16.
AB - A novel artificial receptor has been synthesized using surface-confined
imprinting for the recognition of lysine acetylation in histone H4. The material
has high recognition fidelity and epitope affinity. It was demonstrated that
acetylated Lys plays a role in binding site creation and peptide imprinting can
be performed in phosphate buffer.
PMID- 25848644
TI - Fingerprints of short-range and long-range structure in BaZr(1-x)HfxO3 solid
solutions: an experimental and theoretical study.
AB - A microwave-assisted hydrothermal method was applied to synthesize BaZr1-xHfxO3,
(BZHO) solid solutions at a low temperature, 140 degrees C, and relatively short
times, 160 min. The detailed features of the crystal structure, at both short and
long ranges, as well as the crystal chemistry doping process, are extensively
analysed. X-ray diffraction measurements and Raman spectroscopy have been used to
confirm that pure and Hf-doped BZO materials present a cubic structure. Extended
X-ray absorption fine structure (EXAFS) spectra indicate that Hf(4+) ions have
replaced the Zr(4+) ions on the 6-fold coordination and a subsequent change on
the Ba(2+) 12-fold coordination can be sensed. X-ray absorption near-edge
structure (XANES) spectroscopy measurements reveal a local symmetry breaking
process, associated to overlap of the 4d-2p and 5d-2p orbitals of Zr-O and Hf-O
bonds, respectively. Field emission scanning electron microscopy (FE-SEM) and
high resolution transmission electron microscopy (HRTEM) show the mesocrystalline
nature of self-assembled BZHO nanoparticles under a dodecahedron shape. In
addition first principle calculations were performed to complement the
experimental data. The analysis of the band structures and density of states of
the undoped BZO and doped BZHO host lattice allow deep insight into the main
electronic features. The theoretical results help us to find a correlation
between simulated and experimental Raman modes and allow a more substantial
interpretation of crystal structure.
PMID- 25848645
TI - Modulation of band gap by an applied electric field in silicene-based hetero
bilayers.
AB - Electronic properties of the hetero-structures consisting of silicene, graphene
and BN monolayers under the influence of an electric field were investigated
using density functional theory. With no electric field, both silicene/graphene
and silicene/BN were shown to have a finite gap of about ~50 meV, though silicene
is a zero-gap two-dimensional material. Application of the field perpendicular to
the bilayer system was found to facilitate modulation of the band gap, exhibiting
an approximately linear relationship with the gap energy, in contrast to what was
seen for the constituent monolayers. Also, the degree of the modulation was
mainly determined by the Si-pz electronic states at the interface of the
silicene/graphene and silicene/BN bilayers.
PMID- 25848646
TI - Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) based nanocomposites: influence of
the microstructure on the barrier properties.
AB - Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB-co-4HB) films containing
various contents of organo-modified montmorillonite C30B nanoclays were prepared
by melt intercalation. Wide angle X-ray diffraction measurements and transmission
electron microscopy observations evidenced aggregated and intercalated structures
with individual nanoclay platelets in the nanocomposites and an orientation of
nanoclays. Differential scanning calorimetry measurements showed that the
nanoclay did not influence the crystalline structure of the matrix because it is
mainly located in the polymer amorphous phase. The influence of the filler on the
barrier properties of the film was evaluated by water diffusion, gas permeation
(CO2, N2, O2) and liquid water sorption measurements. A decrease of the N2
permeability was measured due to the tortuosity effect of the filler associated
with a decrease of the solubility within the matrix. The influence of the filler
was more marked for O2 due to the larger decrease of O2 solubility. In contrast,
the CO2 permeability increased whatever the filler content because of a
facilitated transport mechanism due induced by the presence of quaternary
ammonium cations on the C30B surface. The decrease of the water permeability with
the filler was explained by a competition between the kinetic (diffusivity) and
thermodynamic (solubility) contributions defining the permeability process.
PMID- 25848647
TI - Phase control of a perovskite transition-metal oxide through oxygen displacement
at the heterointerface.
AB - Controlling structural distortions that are closely related to functional
properties in transition-metal oxides is a key not only to exploring novel
phenomena but also to developing novel oxide-based electronic devices. In this
review article, we overview investigations revealing that oxygen displacement at
the heterointerface is a key parameter characterizing structure-property
relationships of heterostructures. We further demonstrate that the interface
engineering of the oxygen displacement is useful to control structural and
electronic properties of strained oxides.
PMID- 25848648
TI - Synthesis and characterization of three amino-functionalized metal-organic
frameworks based on the 2-aminoterephthalic ligand.
AB - The incorporation of Lewis base sites and open metal cation sites into metal
organic frameworks (MOFs) is a potential route to improve selective CO2
adsorption from gas mixtures. In this study, three novel amino-functionalized
metal-organic frameworks (MOFs): Mg-ABDC [Mg3(ABDC)3(DMF)4], Co-ABDC
[Co3(ABDC)3(DMF)4] and Sr-ABDC [Sr(ABDC)(DMF)] (ABDC = 2-aminoterephthalate) were
synthesized by solvothermal reactions of 2-aminoterephthalic acid (H2ABDC) with
magnesium, cobalt and strontium metal centers, respectively. Single-crystal
structure analysis showed that Mg-ABDC and Co-ABDC were isostructural compounds
comprising two-dimensional layered structures. The Sr-ABDC contained a three
dimensional motif isostructural to its known Ca analogue. The amino
functionalized MOFs were characterized by powder X-ray diffraction, thermal
gravimetric analysis and N2 sorption. The CO2 and N2 equilibrium adsorption
capacities were measured at different temperatures (0 and 25 degrees C). The
CO2/N2 selectivities of the MOFs were 396 on Mg-ABDC, 326 on Co-ABDC and 18 on Sr
ABDC. Both Mg-ABDC and Co-ABDC exhibit high heat of CO2 adsorption (>30 kJ mol(
1)). The Sr-ABDC displays good thermal stability but had a low adsorption
capacity resulting from narrow pore apertures.
PMID- 25848649
TI - Effects of dry heating on the progression of in vitro digestion of egg white
proteins: contribution of multifactorial data analysis.
AB - The impact of dry heating on the progression of in vitro digestion of egg white
proteins was investigated through application of multiple factor analysis (MFA)
to electrophoresis data. Dry heating (from 1 to 10 days between 60 and 90
degrees C) enhanced protein unfolding and aggregation, thus generating different
SDS-PAGE patterns for each sample before digestion. The progression of in vitro
digestion was then modified according to the degree of protein unfolding and/or
aggregation. In vitro digestion tended to decrease the heterogeneity of sample
electrophoretic patterns overall but it occurred either at the very beginning of
the gastric stage or throughout the gastric stage or again during the duodenal
stage, depending on the heat treatment to which the sample had been subjected. At
the end of digestion, three groups of samples were obtained: all samples dry
heated at 60 degrees C and one sample dry heated for 1 day at 70 degrees C that
were more hydrolysed than the control, samples dry heated for more than 2 days at
80 degrees C or 90 degrees C that were less hydrolysed than the control, and
samples dry heated for more than 2 days at 70 degrees C or 1 day at 80 or 90
degrees C that were as hydrolysed as the control.
PMID- 25848651
TI - Fast identification and quantification of BTEX coupling by Raman spectrometry and
chemometrics.
AB - Monoaromatic hydrocarbons (MAHs) monitoring is of environmental interest since
these chemical pollutants are omnipresent. While waiting for robust sensors able
to detect hydrocarbons at very low levels, the present study shows how each
compound from pure BTEX mixtures can be identified fast and quantified thanks to
Raman spectrometry and data processing based on the SIMPLISMA algorithm. A
preprocessing module has been created to remove background contributions and a
postprocessing program has been added to achieve matching and calibration. A wide
range of BTEX concentrations and relative proportions has been investigated in
order to determine the limitations of the processing. Output results achieved an
accuracy of up to 95%. This method could be extended to other important
pollutants such as polyaromatic hydrocarbons (PAHs) and chlorinated hydrocarbon
derivatives.
PMID- 25848652
TI - Direct arsenic(III) sensing by a renewable gold plated Ir-based microelectrode.
AB - We aim to determine arsenic(III) in natural aquatic systems in the nanomolar
range and at natural pH. In view of a future application of a gel integrated
electrochemical detection approach to reduce fouling and to control mass
transport, we introduce here a microelectrode capable of quantifying As(III) that
consists of a gold plated Ir-based microelectrode (Au-IrM). The key advantage of
this approach is the ability to renew the Au layer by electrochemical control for
better robustness in the field. The microsensor was electrochemically
characterized by Square Wave Anodic Stripping Voltammetry. The obtained results
demonstrate that the stripping peaks exhibit reproducible linear calibration
curves at pH 8 for As(III) concentrations from 10 to 50 nM and from 1 to 10 nM,
using 3 and 36 min preconcentration times, respectively. The interference by
copper and chloride is negligible for an As : Cu concentration ratio of 1 : 20
and a chloride concentration of 0.6 M typically found in seawater. The gold layer
exhibits a lifetime of 7 days. The measurements are reproducible over time for a
given gold layer (RSD < 9%) and between renewed layers (RSD <= 12.5%). While this
work forms the basis for further progress on gel coated microelectrode arrays,
As(III) detection in freshwater samples was successfully demonstrated here.
PMID- 25848650
TI - Modeling and analysis of innate immune responses induced by the host cells
against hepatitis C virus infection.
AB - An in-depth understanding of complex systems such as hepatitis C virus (HCV)
infection and host immunomodulatory response is an open challenge for biologists.
In order to understand the mechanisms involved in immune evasion by HCV, we
present a simplified formalization of the highly dynamic system consisting of
HCV, its replication cycle and host immune responses at the cellular level using
hybrid Petri net (HPN). The approach followed in this study comprises of step
wise simulation, model validation and analysis of host immune response. This
study was performed with an objective of making correlations among viral RNA
levels, interferon (IFN) production and interferon stimulated genes (ISGs)
induction. The results correlate with the biological data verifying that the
model is very useful in predicting the dynamic behavior of the signaling proteins
in response to a stimulus. This study implicates that HCV infection is dependent
upon several key factors of the host immune response. The effect of host proteins
on limiting viral infection is effectively overruled by the viral pathogen. This
study also analyzes activity levels of RNase L, miR-122, IFN, ISGs and PKR
induction and inhibition of TLR3/RIG1 mediated pathways in response to targeted
manipulation in the presence of HCV. The results are in complete agreement at the
time of writing with the published expression studies and western blot
experiments. Our model also provides some biological insights regarding the role
of PKR in the acute infection of HCV. It might help to explain why many patients
fail to clear acute HCV infection while others, with low ISG basal levels, clear
HCV spontaneously. The described methodology can easily be reproduced, which
suitably supports the study of other viral infections in a formal, automated and
expressive manner. The Petri net-based modeling approach applied here may provide
valuable insights for study design and analyses to evaluate other disease
associated integrated pathways in biological systems.
PMID- 25848653
TI - Polymeric catenanes synthesized via "click" chemistry and atom transfer radical
coupling.
AB - A novel route for the synthesis of polymeric catenanes was demonstrated by
grafting an alkyne functionalized polymer onto a supramolecularly templated azide
terminated ligand followed by ring closure via atom transfer radical coupling
(ATRC). The polymeric catenane was characterized via GPC and AFM imaging.
PMID- 25848654
TI - Growth rates and water stability of 2D boronate ester covalent organic
frameworks.
AB - We examine the growth rates, activation energies, and hydrolytic stability of
multiple 2D boronate ester covalent organic frameworks by turbidity measurements,
observing a 200-fold range in stability. The rate-determining step in boronate
ester 2D COF growth is not in-solution condensation, but rather interlayer
polymer stacking through a nucleation-elongation process.
PMID- 25848655
TI - Spontaneous assembly of silylethane-thiol derivatives on Au(111): a chemically
robust thiol protecting group as the precursor for the direct formation of
aromatic gold thiolate monolayers.
AB - Self-assembled monolayers (SAMs) on gold were obtained by the direct absorption
of a fully conjugated phenylenethienylene derivative () presenting robust
silylethane-thiol protecting groups as anchoring agents. The thiol deprotection
and SAM formation have been evidenced by quartz crystal microbalance (QCM)
measurements and X-ray photoelectron spectroscopy (XPS), and have been compared
to the SAM obtained from its thioacetate analog (5). The chemically robust
silylethane-thiol protecting group appeared as a surprisingly effective anchoring
agent for the preparation of aromatic SAMs on Au(111), suitable for subsequent
post-functionalization.
PMID- 25848656
TI - Statistical carbazole-fluorene-TTBTBTT terpolymers as promising electron donor
materials for organic solar cells.
AB - We report the application of a statistical Suzuki-Miyaura polycondensation
reaction for synthesis of a family of carbazole-fluorene-TTBTBTT terpolymers with
tailored physical and optoelectronic properties. Organic bulk heterojunction
solar cells based on the designed materials with optimal fluorene to carbazole
ratios yielded reproducible power conversion efficiencies of 6.5-6.7%.
PMID- 25848657
TI - 3,4,9,10-Perylenetetracarboxylic acid/o-phenylenediamine nanomaterials as novel
redox probes for electrochemical aptasensor systems based on an Fe3O4 magnetic
bead as a nonenzymatic catalyst.
AB - A novel redox probe 3,4,9,10-perylenetetracarboxylic acid/o-phenylenediamine
(PTCA/OPD) with well-defined redox peaks caused by the synergistic action between
them was demonstrated via theoretical and practical research, and applied in an
electrochemical aptasensor to detect thrombin (TB) based on an Fe3O4 magnetic
bead (MB) as a nonenzymatic catalyst.
PMID- 25848658
TI - Carbon cladded TiO2 nanotubes: fabrication and use in 3D-RuO2 based
supercapacitors.
AB - In this work we introduce a facile procedure that allows a highly conformal
coating of self-organized TiO2 nanotubes (NTs) with a graphite-like thin carbon
layer. This provides a platform to enhance the functionality of TiO2 nanotubes
for a wide range of applications. Here we show that such modified nanotubes can
serve as a 3D scaffold for an ideal decoration with RuO2 nanoparticles. Used as
3D pseudocapacitor electrode, capacitance values of up to 80 times higher than
plain TiO2 NTs, and a very high yield of utilization of RuO2 (872 F g(-1)) and
excellent long-term cycling stability can be reached.
PMID- 25848659
TI - Investigating dendrites and side reactions in sodium-oxygen batteries for
improved cycle lives.
AB - The development of sodium-oxygen batteries with high round-trip efficiencies is
hindered by the short cycle lives. Sodium dendrite formation and oxygen crossover
are identified as two major issues. By employing an ion selective membrane, the
cycle life of sodium-oxygen batteries has been greatly improved.
PMID- 25848660
TI - The pWW0 plasmid imposes a stochastic expression regime to the chromosomal ortho
pathway for benzoate metabolism in Pseudomonas putida.
AB - Environmental plasmids often expand the metabolic repertoire of bacteria that
carry them, but they also interfere with the biochemical and genetic network of
the host. The pWW0 plasmid born by Pseudomonas putida mt-2 encodes the TOL
pathway for degradation of toluene/m-xylene through production of intermediate
compounds benzoate/3-methylbenzoate. These can be also recognized as substrates
by the chromosomally encoded ben and cat gene products, thereby creating a
manifest regulatory and biochemical conflict. In this context, we have
investigated how the introduction of the pWW0 plasmid into P. putida affects
behaviour of the promoter of the ben pathway (Pb) in single cells. Using a series
of standardized transcriptional fusions to green fluorescent protein, we found
that acquisition of the TOL pathway switches the activation course of the Pb
promoter from unimodal/graded to bimodal/stochastic when cells were exposed to
benzoate. This behaviour was propagated downstream into the Pc promoter of the
cat gene cluster, which responds to the benzoate-degradation intermediate cis,cis
muconate. The TOL plasmid thus imposes expression of the chromosomal Pb with a
stochastic behaviour likely to result in biochemical heterogeneity of the
otherwise genetically clonal population when exposed to benzoate as a growth
substrate.
PMID- 25848661
TI - Preface. Rhodopsin.
PMID- 25848662
TI - Preface. PCR primer design.
PMID- 25848663
TI - Reply: To PMID 23940103.
PMID- 25848664
TI - Reply: To PMID 24401738.
PMID- 25848665
TI - Allison Doupe: in memoriam.
PMID- 25848666
TI - Kidney transplantation - the journey continues.
PMID- 25848667
TI - Hypersexuality after self-inflicted nail gun penetrating traumatic brain injury
and neurosurgery: case analysis with literature review.
PMID- 25848668
TI - [Discovering innovations].
PMID- 25848669
TI - Decisions about knowledge in medical practice: the effect of temporal features of
a task.
AB - A classic question of social science is how knowledge informs practice. Research
on physicians' decisions about medical knowledge has focused on doctors' personal
capabilities and features of the knowledge corpus, producing divergent findings.
This study asks, instead, How is decision making about the use of knowledge
influenced by features of work? From observations of one team's decisions in
multiple clinical and administrative contexts, the author argues that making
decisions is contingent upon temporal features of physicians' tasks. Physicians
receive feedback at different speeds, and they must account for these speeds when
judging what they can prioritize. This finding explains doctors' perceived
uncertainty in other studies as a product of the long feedback loop in tasks, and
their certainty or pragmatism as a product of shorter feedback loops. In these
latter scenario's, physicians consider and deploy scientific knowledge after--and
not before, as is usually assumed--determining a fruitful plan of action.
PMID- 25848670
TI - Racially and ethnically diverse schools and adolescent romantic relationships.
AB - Focusing on romantic relationships, which are often seen as a barometer of social
distance, this analysis investigates how adolescents from different racial-ethnic
and gender groups respond when they attend diverse schools with many
opportunities for inter-racial-ethnic dating. Which groups respond by forming
inter-racial-ethnic relationships, and which groups appear to "work around"
opportunities for inter-racial-ethnic dating by forming more same-race-ethnicity
relationships outside of school boundaries? Most prior studies have analyzed only
relationships within schools and, therefore, cannot capture a potentially
important way that adolescents express preferences for same-race-ethnicity
relationships or work around constraints from other groups' preferences. Using
the National Longitudinal Study of Adolescent Health, I find that, when
adolescents are in schools with many opportunities for inter-racial-ethnic
dating, black females and white males are most likely to form same-race-ethnicity
relationships outside of the school; whereas Hispanic males and females are most
likely to date across racial-ethnic boundaries within the school.
PMID- 25848671
TI - Who is black, white, or mixed race? How skin color, status, and nation shape
racial classification in Latin America.
AB - Comparative research on racial classification has often turned to Latin America,
where race is thought to be particularly fluid. Using nationally representative
data from the 2010 and 2012 America's Barometer survey, the authors examine
patterns of self-identification in four countries. National differences in the
relation between skin color, socioeconomic status, and race were found. Skin
color predicts race closely in Panama but loosely in the Dominican Republic.
Moreover, despite the dominant belief that money whitens, the authors discover
that status polarizes (Brazil), mestizoizes (Colombia), darkens (Dominican
Republic), or has no effect (Panama). The results show that race is both physical
and cultural, with country variations in racial schema that reflect specific
historical and political trajectories.
PMID- 25848672
TI - Sources of sibling (dis)similarity: total family impact on status variation in
The Netherlands in the nineteenth century.
AB - The authors describe and explain variation in the occupational status resemblance
of brothers in The Netherlands during modernization. They test opposing
hypotheses about how modernization processes influenced fraternal resemblance
through the value and inequality of family resources based on a job competition
model in combination with modernization theory, status maintenance theory, and
dualism theory. The authors use the high-quality, large-scale database GENLIAS,
yielding digitized information for approximately 450,000 linked Dutch marriage
certificates from 250,000 families, complemented with historical indicators of
six modernization processes for over 2,500 communities. Using multilevel meta
regression models, they find that brother correlations in status decreased slowly
from about 1860 onward. Although this exactly parallels the period of
modernization, the authors find that modernization processes were not responsible
(except possibly urbanization and mass transportation). In fact, in line with
dualism theory, fraternal resemblance increased with most processes (i.e.,
industrialization, educational expansion, in-migration, and mass communication)
because they amplified in-equality.
PMID- 25848675
TI - Effect of acceptor strength on optical and electronic properties in conjugated
polymers for solar applications.
AB - Four new low-bandgap electron-accepting polymers-poly(4,10-bis(2-butyloctyl)-2-(2
(2-ethylhexyl)-1,1-dioxido-3-oxo-2,3-dihydrothieno[3,4-d]isothiazol-4
yl)thieno[2',3':5,6]pyrido[3,4-g]thieno[3,2-c]isoquinoline-5,11(4H,10H-dione)
(PNSW); poly(4,10-bis(2-butyloctyl)-2-(5-(2-ethylhexyl)-4,6-dioxo-5,6-dihydro-4H
thieno[3,4-c]pyrrol-1-yl)thieno[2',3':5,6]pyrido[3,4-g]thieno[3,2-c]isoquinoline
5,11(4H,10H)-dione) (PNTPD); poly(5-(4,10-bis(2-butyloctyl)-5,11-dioxo-4,5,10,11
tetrahydrothieno[2',3':5,6]pyrido[3,4-g]thieno[3,2-c]isoquinolin-2-yl)-2,9-bis(2
decyldodecyl)anthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)
tetraone) (PNPDI); and poly(9,9-bis(2-butyloctyl)-9H-fluorene-bis((1,10:5,6)2
(5,6-dihydro-4H-cyclopenta[b]thiophene-4-ylidene)malonitrile)-2-(2,3
dihydrothieno[3,4-b][1,4]dioxine)) (PECN)-containing
thieno[2',3':5',6']pyrido[3,4-g]thieno[3,2-c]isoquinoline-5,11(4H,10H)-dione and
fluorenedicyclopentathiophene dimalononitrile, were investigated to probe their
structure-function relationships for solar cell applications. PTB7 was also
investigated for comparison with the new low-bandgap polymers. The steady-state,
ultrafast dynamics and nonlinear optical properties of all the organic polymers
were probed. All the polymers showed broad absorption in the visible region, with
the absorption of PNPDI and PECN extending into the near-IR region. The polymers
had HOMO levels ranging from -5.73 to -5.15 eV and low bandgaps of 1.47-2.45 eV.
Fluorescence upconversion studies on the polymers showed long lifetimes of 1.6
and 2.4 ns for PNSW and PNTPD, respectively, while PNPDI and PECN showed very
fast decays within 353 and 110 fs. PECN exhibited a very high two-photon
absorption cross section. The electronic structure calculations of the repeating
units of the polymers indicated the localization of the molecular orbitals in
different co-monomers. As the difference between the electron affinities of the
co-monomers in the repeating units decreases, the highest occupied and lowest
unoccupied molecular orbitals become more distributed. All the measurements
suggest that a large difference in the electron affinities of the co-monomers of
the polymers contributes to the improvement of the photophysical properties
necessary for highly efficient solar cell performance. PECN exhibited excellent
photophysical properties, which makes it to be a good candidate for solar cell
device applications.
PMID- 25848674
TI - A genome-wide analysis of MADS-box genes in peach [Prunus persica (L.) Batsch].
AB - BACKGROUND: MADS-box genes encode a family of eukaryotic transcription factors
distinguished by the presence of a highly-conserved ~58 amino acid DNA-binding
and dimerization domain (the MADS-box). The central role played by MADS-box genes
in peach endodormancy regulation led us to examine this large gene family in more
detail. We identified the locations and sequences of 79 MADS-box genes in peach,
separated them into established subfamilies, and broadly surveyed their tissue
specific and dormancy-induced expression patterns using next-generation
sequencing. We then focused on the dormancy-related SVP/AGL24 and FLC
subfamilies, comparing their numbers and phylogenetic relationships with those of
other sequenced woody perennial genomes. RESULTS: We identified 79 MADS-box genes
distributed across all eight peach chromosomes and frequently located in clusters
of two or more genes. They encode proteins with a mean length of 248 +/- 72 amino
acids and include representatives from most of the thirteen Type II (MIKC)
subfamilies, as well as members of the Type I Malpha, Mbeta, and Mgamma
subfamilies. Most Type I genes were present in species-specific monophyletic
lineages, and their expression in the peach sporophyte was low or absent. Most
Type II genes had Arabidopsis orthologs and were expressed at much higher levels
throughout vegetative and fruit tissues. During short-day-induced growth
cessation, seven Type II genes from the SVP/AGL24, AGL17, and SEP subfamilies
showed significant changes in expression. Phylogenetic analyses indicated that
multiple, independent expansions have taken place within the SVP/AGL24 and FLC
lineages in woody perennial species. CONCLUSIONS: Most Type I genes appear to
have arisen through tandem duplications after the divergence of the Arabidopsis
and peach lineages, whereas Type II genes appear to have increased following
whole genome duplication events. An exception to the latter rule occurs in the
FLC and SVP/AGL24 Type II subfamilies, in which species-specific tandem
duplicates have been retained in a number of perennial species. These subfamilies
comprise part of a genetic toolkit that regulates endodormancy transitions, but
phylogenetic and expression data suggest that individual orthologs may not
function identically across all species.
PMID- 25848676
TI - Bioactivation of Phytoestrogens: Intestinal Bacteria and Health.
AB - Phytoestrogens are polyphenols similar to human estrogens found in plants or
derived from plant precursors. Phytoestrogens are found in high concentration in
soya, flaxseed and other seeds, fruits, vegetables, cereals, tea, chocolate, etc.
They comprise several classes of chemical compounds (stilbenes, coumestans,
isoflavones, ellagitannins, and lignans) which are structurally similar to
endogenous estrogens but which can have both estrogenic and antiestrogenic
effects. Although epidemiological and experimental evidence indicates that intake
of phytoestrogens in foods may be protective against certain chronic diseases,
discrepancies have been observed between in vivo and in vitro experiments. The
microbial transformations have not been reported so far in stilbenes and
coumestans. However, isoflavones, ellagitanins, and lignans are metabolized by
intestinal bacteria to produce equol, urolithins, and enterolignans,
respectively. Equol, urolithin, and enterolignans are more bioavailable, and have
more estrogenic/antiestrogenic and antioxidant activity than their precursors.
Moreover, equol, urolithins and enterolignans have anti-inflammatory effects and
induce antiproliferative and apoptosis-inducing activities. The transformation of
isoflavones, ellagitanins, and lignans by intestinal microbiota is essential to
be protective against certain chronic diseases, as cancer, cardiovascular
disease, osteoporosis, and menopausal symptoms. Bioavailability, bioactivity, and
health effects of dietary phytoestrogens are strongly determined by the
intestinal bacteria of each individual.
PMID- 25848677
TI - Metabolic learning and memory formation by the brain influence systemic metabolic
homeostasis.
AB - Metabolic homeostasis is regulated by the brain, but whether this regulation
involves learning and memory of metabolic information remains unexplored. Here we
use a calorie-based, taste-independent learning/memory paradigm to show that
Drosophila form metabolic memories that help in balancing food choice with
caloric intake; however, this metabolic learning or memory is lost under chronic
high-calorie feeding. We show that loss of individual learning/memory-regulating
genes causes a metabolic learning defect, leading to elevated trehalose and lipid
levels. Importantly, this function of metabolic learning requires not only the
mushroom body but also the hypothalamus-like pars intercerebralis, while NF
kappaB activation in the pars intercerebralis mimics chronic overnutrition in
that it causes metabolic learning impairment and disorders. Finally, we evaluate
this concept of metabolic learning/memory in mice, suggesting that the
hypothalamus is involved in a form of nutritional learning and memory, which is
critical for determining resistance or susceptibility to obesity. In conclusion,
our data indicate that the brain, and potentially the hypothalamus, direct
metabolic learning and the formation of memories, which contribute to the control
of systemic metabolic homeostasis.
PMID- 25848678
TI - Platelet-Rich Plasma Prolongs Myofibroblast Accumulation in Corneal Stroma with
Incisional Wound.
AB - PURPOSE: The purpose of this study was to determine whether platelet-rich plasma
(PRP) has an effect on corneal stromal cells in a rat model of wound healing
following corneal incision. MATERIALS AND METHODS: The effect of PRP on corneal
wound healing in vivo was investigated in a corneal incision wound model in rats.
40 rats were wounded by deep corneal incision, and treated with either topically
administered PRP (20 rats) or sodium chloride (20 rats). At 4 h and 1, 3, and 5
days after incision, alpha-smooth muscle actin (alpha SMA), SMAD2 and SMAD3
expression and apoptosis in stromal cells were evaluated by immunohistochemistry,
and IL-1beta mRNA expression was evaluated by real time PCR. RESULTS: PRP-treated
corneas exhibited reduced stromal cell apoptosis at day 3 and day 5 (p = 0.038,
and <0.001, respectively) relative to controls. Interleukin-1beta mRNA
expression, however, was unchanged in PRP-treated corneas relative to controls.
Topical PRP treatment resulted in a higher proportion of alphaSMA-positive
myofibroblasts recruited to the wound site relative to control corneas. PRP did
not affect activation of SMAD2 but activation of SMAD3 was significantly reduced
at day 1 (p = 0.001) and dramatically increased at day 5 (p = 0.032).
CONCLUSIONS: PRP treatment resulted in suppressed stromal cell apoptosis followed
by SMAD3 activation and a greater proportion of myofibroblasts present at the
wound site. Suppression of stromal cell apoptosis after corneal wounding by use
of a growth factor-rich formulation may lead to myofibroblast accumulation by
modulation of the TGF-beta pathway.
PMID- 25848679
TI - Enhanced Reactivity in Hydrogen Atom Transfer from Tertiary Sites of Cyclohexanes
and Decalins via Strain Release: Equatorial C-H Activation vs Axial C-H
Deactivation.
AB - Absolute rate constants for hydrogen atom transfer (HAT) from cycloalkanes and
decalins to the cumyloxyl radical (CumO(*)) were measured by laser flash
photolysis. Very similar reactivities were observed for the C-H bonds of
cyclopentane and cyclohexane, while the tertiary C-H bond of methylcyclopentane
was found to be 6 times more reactive than the tertiary axial C-H bond of
methylcyclohexane, pointing toward a certain extent of tertiary axial C-H bond
deactivation. Comparison between the cis and trans isomers of 1,2
dimethylcyclohexane, 1,4-dimethylcyclohexane and decalin provides a quantitative
evaluation of the role played by strain release in these reactions. kH values for
HAT from tertiary equatorial C-H bonds were found to be at least 1 order of
magnitude higher than those for HAT from the corresponding tertiary axial C-H
bonds (kH(eq)/kH(ax) = 10-14). The higher reactivity of tertiary equatorial C-H
bonds was explained in terms of 1,3-diaxial strain release in the HAT transition
state. Increase in torsional strain in the HAT transition state accounts instead
for tertiary axial C-H bond deactivation. The results are compared with those
obtained for the corresponding C-H functionalization reactions by dioxiranes and
nonheme metal-oxo species indicating that CumO(*) can represent a convenient
model for the reactivity patterns of these oxidants.
PMID- 25848680
TI - Chronic exposure of diesel exhaust particles induces alveolar enlargement in
mice.
AB - BACKGROUND: Diesel exhaust particles (DEPs) are deposited into the respiratory
tract and are thought to be a risk factor for the development of diseases of the
respiratory system. In healthy individuals, the timing and mechanisms of
respiratory tract injuries caused by chronic exposure to air pollution remain to
be clarified. METHODS: We evaluated the effects of chronic exposure to DEP at
doses below those found in a typical bus corridor in Sao Paulo (150 MUg/m3). Male
BALB/c mice were divided into mice receiving a nasal instillation: saline
(saline; n = 30) and 30 MUg/10 MUL of DEP (DEP; n = 30). Nasal instillations were
performed five days a week, over a period of 90 days. Bronchoalveolar lavage
(BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13
and interferon-gamma (INF-gamma) were determined by ELISA-immunoassay. Assessment
of respiratory mechanics was performed. The gene expression of Muc5ac in lung was
evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T
cells and CD20+ B cells in tissues was analysed by immunohistochemistry.
Bronchial thickness and the collagen/elastic fibers density were evaluated by
morphometry. We measured the mean linear intercept (Lm), a measure of alveolar
distension, and the mean airspace diameter (D0) and statistical distribution
(D2). RESULTS: DEP decreased IFN-gamma levels in BAL (p = 0.03), but did not
significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell
and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p <=
0.001) and CD8+ T cells (p <= 0.001) increased in the parenchyma. Although IL-13
(p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene
expression was not altered in the lung of DEP-exposed animals. Although
respiratory mechanics, elastic and collagen density were not modified, the mean
linear intercept (Lm) was increased in the DEP-exposed animals (p <= 0.001), and
the index D2 was statistically different (p = 0.038) from the control animals.
CONCLUSION: Our data suggest that nasal instillation of low doses of DEP over a
period of 90 days results in alveolar enlargement in the pulmonary parenchyma of
healthy mice.
PMID- 25848682
TI - Read My Lips: Brain Dynamics Associated with Audiovisual Integration and Deviance
Detection.
AB - Information from different modalities is initially processed in different brain
areas, yet real-world perception often requires the integration of multisensory
signals into a single percept. An example is the McGurk effect, in which people
viewing a speaker whose lip movements do not match the utterance perceive the
spoken sounds incorrectly, hearing them as more similar to those signaled by the
visual rather than the auditory input. This indicates that audiovisual
integration is important for generating the phoneme percept. Here we asked when
and where the audiovisual integration process occurs, providing spatial and
temporal boundaries for the processes generating phoneme perception.
Specifically, we wanted to separate audiovisual integration from other processes,
such as simple deviance detection. Building on previous work employing ERPs, we
used an oddball paradigm in which task-irrelevant audiovisually deviant stimuli
were embedded in strings of non-deviant stimuli. We also recorded the event
related optical signal, an imaging method combining spatial and temporal
resolution, to investigate the time course and neuroanatomical substrate of
audiovisual integration. We found that audiovisual deviants elicit a short
duration response in the middle/superior temporal gyrus, whereas audiovisual
integration elicits a more extended response involving also inferior frontal and
occipital regions. Interactions between audiovisual integration and deviance
detection processes were observed in the posterior/superior temporal gyrus. These
data suggest that dynamic interactions between inferior frontal cortex and
sensory regions play a significant role in multimodal integration.
PMID- 25848681
TI - "The Cooties Effect": Amygdala Reactivity to Opposite- versus Same-sex Faces
Declines from Childhood to Adolescence.
AB - One of the most important social identities that children learn to define
themselves and others by is sex, becoming a salient social category by early
childhood. Although older children begin to show greater flexibility in their
gendered behaviors and attitudes, gender rigidity intensifies again around the
time of puberty. In the current study, we assessed behavioral and neural biases
to sex across a wide age group. Ninety-three youth (ages 7-17 years) provided
behavioral rating of same- and opposite-sex attitudes, and 52 youth (ages 4-18
years) underwent an fMRI scan as they matched the emotion of same- and opposite
sex faces. We demonstrate significant age-related behavioral biases of sex that
are mediated by differential amygdala response to opposite-sex relative to same
sex faces in children, an effect that completely attenuates by the teenage years.
Moreover, we find a second peak in amygdala sensitivity to opposite-sex faces
around the time of puberty. Thus, the amygdala codes for developmentally
dependent and motivationally relevant social identification across development.
PMID- 25848683
TI - Early Visual Word Processing Is Flexible: Evidence from Spatiotemporal Brain
Dynamics.
AB - Visual word recognition is often described as automatic, but the functional locus
of top-down effects is still a matter of debate. Do task demands modulate how
information is retrieved, or only how it is used? We used EEG/MEG recordings to
assess whether, when, and how task contexts modify early retrieval of specific
psycholinguistic information in occipitotemporal cortex, an area likely to
contribute to early stages of visual word processing. Using a parametric
approach, we analyzed the spatiotemporal response patterns of occipitotemporal
cortex for orthographic, lexical, and semantic variables in three
psycholinguistic tasks: silent reading, lexical decision, and semantic decision.
Task modulation of word frequency and imageability effects occurred
simultaneously in ventral occipitotemporal regions-in the vicinity of the
putative visual word form area-around 160 msec, following task effects on
orthographic typicality around 100 msec. Frequency and typicality also produced
task-independent effects in anterior temporal lobe regions after 200 msec. The
early task modulation for several specific psycholinguistic variables indicates
that occipitotemporal areas integrate perceptual input with prior knowledge in a
task-dependent manner. Still, later task-independent effects in anterior temporal
lobes suggest that word recognition eventually leads to retrieval of semantic
information irrespective of task demands. We conclude that even a highly
overlearned visual task like word recognition should be described as flexible
rather than automatic.
PMID- 25848684
TI - Rapid Context-based Identification of Target Sounds in an Auditory Scene.
AB - To make sense of our dynamic and complex auditory environment, we must be able to
parse the sensory input into usable parts and pick out relevant sounds from all
the potentially distracting auditory information. Although it is unclear exactly
how we accomplish this difficult task, Gamble and Woldorff [Gamble, M. L., &
Woldorff, M. G. The temporal cascade of neural processes underlying target
detection and attentional processing during auditory search. Cerebral Cortex (New
York, N.Y.: 1991), 2014] recently reported an ERP study of an auditory target
search task in a temporally and spatially distributed, rapidly presented,
auditory scene. They reported an early, differential, bilateral activation
(beginning at 60 msec) between feature-deviating target stimuli and physically
equivalent feature-deviating nontargets, reflecting a rapid target detection
process. This was followed shortly later (at 130 msec) by the lateralized N2ac
ERP activation, that reflects the focusing of auditory spatial attention toward
the target sound and parallels the attentional-shifting processes widely studied
in vision. Here we directly examined the early, bilateral, target-selective
effect to better understand its nature and functional role. Participants listened
to midline-presented sounds that included target and nontarget stimuli that were
randomly either embedded in a brief rapid stream or presented alone. The results
indicate that this early bilateral effect results from a template for the target
that utilizes its feature deviancy within a stream to enable rapid
identification. Moreover, individual-differences analysis showed that the size of
this effect was larger for participants with faster RTs. The findings support the
hypothesis that our auditory attentional systems can implement and utilize a
context-based relational template for a target sound, making use of additional
auditory information in the environment when needing to rapidly detect a relevant
sound.
PMID- 25848685
TI - Multivariate fMRI and Eye Tracking Reveal Differential Effects of Visual
Interference on Recognition Memory Judgments for Objects and Scenes.
AB - Recent work has demonstrated that the perirhinal cortex (PRC) supports
conjunctive object representations that aid object recognition memory following
visual object interference. It is unclear, however, how these representations
interact with other brain regions implicated in mnemonic retrieval and how
congruent and incongruent interference influences the processing of targets and
foils during object recognition. To address this, multivariate partial least
squares was applied to fMRI data acquired during an interference match-to-sample
task, in which participants made object or scene recognition judgments after
object or scene interference. This revealed a pattern of activity sensitive to
object recognition following congruent (i.e., object) interference that included
PRC, prefrontal, and parietal regions. Moreover, functional connectivity analysis
revealed a common pattern of PRC connectivity across interference and recognition
conditions. Examination of eye movements during the same task in a separate study
revealed that participants gazed more at targets than foils during correct object
recognition decisions, regardless of interference congruency. By contrast,
participants viewed foils more than targets for incorrect object memory
judgments, but only after congruent interference. Our findings suggest that
congruent interference makes object foils appear familiar and that a network of
regions, including PRC, is recruited to overcome the effects of interference.
PMID- 25848686
TI - Mass and Charge Transport in the Polymer-Ionic-Liquid System PEO-EMImI: From
Ionic-Liquid-in-Polymer to Polymer-in-Ionic-Liquid Electrolytes.
AB - Conventional polymer electrolytes based on inorganic salts are commonly
characterized and utilized over a small salt-poor composition range because of
phase transitions accompanied by loss of ion conductivity at high salt
concentrations. By contrast, well-chosen polymer-ionic-liquid (IL) systems offer
the possibility to vary the IL content from the IL-in-polymer to the polymer-in
IL domain. We have investigated the temperature-dependent ionic conductivity in
PEOyEMImI systems consisting of poly(ethylene oxide) complexed with 1-ethyl-3
methylimidazolium iodide for y = EO/IL ratios ranging from 0.6 to 60 and compared
diffusivity data with that arising from (1)H pulsed-field-gradient nuclear
magnetic resonance for EMIm and (125)I radiotracer diffusion for iodine.
Surprisingly, the diffusivity of cations and anions vary at most by 50% at fixed
temperatures over the entire composition range. The much larger changes in the
charge diffusivity Dsigma relate to ion pairing exhibiting a minimum near the
intermediate composition y = 10. Altogether, the results are relevant to
application in dye-sensitized solar cells and show that a high ion density is
crucial to enhance the iodine transport capacity.
PMID- 25848688
TI - Studies on formation, control and application of biofilm formed by food related
microorganisms.
AB - Biofilms are sessile microbial aggregates on the interfaces, and they were
usually considered as microbial contamination sources in medical care and various
industries. We studied the control and application of biofilms formed by food
related microorganisms, and mechanism of the biofilm formation was also
investigated. We studied the biofilm formation in mixed cultures using various
combinations of two strains of food-related microorganisms. There were various
microorganisms that showed decreased or increased biofilm formation in the mixed
culture in comparison with that in a single culture. Biofilm formed by lactic
acid bacteria and yeast isolated from traditional fermented food, Fukuyama pot
vinegar, exhibited unique feature in that structure and formation mechanism, and
expected to be used as an immobilized microorganism in fermentation production.
Here our studies on the control and application of biofilms and the mechanisms of
its formation were described.
PMID- 25848687
TI - Comparative metabolic and transcriptional analysis of a doubled diploid and its
diploid citrus rootstock (C. junos cv. Ziyang xiangcheng) suggests its potential
value for stress resistance improvement.
AB - BACKGROUND: Polyploidy has often been considered to confer plants a better
adaptation to environmental stresses. Tetraploid citrus rootstocks are expected
to have stronger stress tolerance than diploid. Plenty of doubled diploid citrus
plants were exploited from diploid species for citrus rootstock improvement.
However, limited metabolic and molecular information related to tetraploidization
is currently available at a systemic biological level. This study aimed to
evaluate the occurrence and extent of metabolic and transcriptional changes
induced by tetraploidization in Ziyang xiangcheng (Citrus junos Sieb. ex Tanaka),
which is a special citrus germplasm native to China and widely used as an iron
deficiency tolerant citrus rootstock. RESULTS: Doubled diploid Ziyang xiangcheng
has typical morphological and anatomical features such as shorter plant height,
larger and thicker leaves, bigger stomata and lower stomatal density, compared to
its diploid parent. GC-MS (Gas chromatography coupled to mass spectrometry)
analysis revealed that tetraploidization has an activation effect on the
accumulation of primary metabolites in leaves; many stress-related metabolites
such as sucrose, proline and gamma-aminobutyric acid (GABA) was remarkably up
regulated in doubled diploid. However, LC-QTOF-MS (Liquid chromatography
quadrupole time-of-flight mass spectrometry) analysis demonstrated that
tetraploidization has an inhibition effect on the accumulation of secondary
metabolites in leaves; all the 33 flavones were down-regulated while all the 6
flavanones were up-regulated in 4x. By RNA-seq analysis, only 212 genes (0.8% of
detected genes) are found significantly differentially expressed between 2x and
4x leaves. Notably, those genes were highly related to stress-response functions,
including responses to salt stress, water and abscisic acid. Interestingly, the
transcriptional divergence could not explain the metabolic changes, probably due
to post-transcriptional regulation. CONCLUSION: Taken together, tetraploidization
induced considerable changes in leaf primary and secondary metabolite
accumulation in Ziyang xiangcheng. However, the effect of tetraploidization on
transcriptome is limited. Compared to diploid, higher expression level of stress
related genes and higher content of stress related metabolites in doubled diploid
could be beneficial for its stress tolerance.
PMID- 25848689
TI - Genetic mapping of centromeres in the nine Citrus clementina chromosomes using
half-tetrad analysis and recombination patterns in unreduced and haploid gametes.
AB - BACKGROUND: Mapping centromere locations in plant species provides essential
information for the analysis of genetic structures and population dynamics. The
centromere's position affects the distribution of crossovers along a chromosome
and the parental heterozygosity restitution by 2n gametes is a direct function of
the genetic distance to the centromere. Sexual polyploidisation is relatively
frequent in Citrus species and is widely used to develop new seedless triploid
cultivars. The study's objectives were to (i) map the positions of the
centromeres of the nine Citrus clementina chromosomes; (ii) analyse the crossover
interference in unreduced gametes; and (iii) establish the pattern of genetic
recombination in haploid clementine gametes along each chromosome and its
relationship with the centromere location and distribution of genic sequences.
RESULTS: Triploid progenies were derived from unreduced megagametophytes produced
by second-division restitution. Centromere positions were mapped genetically for
all linkage groups using half-tetrad analysis. Inference of the physical
locations of centromeres revealed one acrocentric, four metacentric and four
submetacentric chromosomes. Crossover interference was observed in unreduced
gametes, with variation seen between chromosome arms. For haploid gametes, a
strong decrease in the recombination rate occurred in centromeric and
pericentromeric regions, which contained a low density of genic sequences. In
chromosomes VIII and IX, these low recombination rates extended beyond the
pericentromeric regions. The genomic region corresponding to a genetic distance <
5cM from a centromere represented 47% of the genome and 23% of the genic
sequences. CONCLUSIONS: The centromere positions of the nine citrus chromosomes
were genetically mapped. Their physical locations, inferred from the genetic
ones, were consistent with the sequence constitution and recombination pattern
along each chromosome. However, regions with low recombination rates extended
beyond the pericentromeric regions of some chromosomes into areas richer in genic
sequences. The persistence of strong linkage disequilibrium between large numbers
of genes promotes the stability of epistatic interactions and multilocus
controlled traits over successive generations but also maintains multi-trait
associations. Identification of the centromere positions will allow the
development of simple methods to analyse unreduced gamete formation mechanisms in
a large range of genotypes and further modelling of genetic inheritance in sexual
polyploidisation breeding schemes.
PMID- 25848691
TI - Functional Characterization of Long Noncoding RNA Lnc_bc060912 in Human Lung
Carcinoma Cells.
AB - Long noncoding RNAs (lncRNAs) are pervasively transcribed in the human genome.
Recent studies suggest that the involvement of lncRNAs in human diseases could be
far more prevalent than previously appreciated. Here we have identified a lncRNA
termed Lnc_bc060912 whose expression is increased in human lung and other tumors.
Lnc_bc060912 is 1.2 kb in length and is composed of two exons. The expression of
Lnc_bc060912 was repressed by p53. Lnc_bc060912 suppressed cell apoptosis. Using
a recently developed method for RNA-pulldown with formaldehyde cross-linking, we
found that Lnc_bc060912 interacted with the two DNA damage repair proteins PARP1
and NPM1. Together, these results suggest that Lnc_bc060912, via PARP1 and NPM1,
affects cell apoptosis and may play important roles in tumorigenesis and cancer
progression.
PMID- 25848690
TI - The OsSec18 complex interacts with P0(P1-P2)2 to regulate vacuolar morphology in
rice endosperm cell.
AB - BACKGROUND: Sec18p/N-ethylmaleimide-sensitive factor (NSF) is a conserved
eukaryotic ATPase, which primarily functions in vesicle membrane fusion from
yeast to human. However, the function of the OsSec18 gene, a homologue of NSF in
rice, remains unknown. RESULTS: In the present study, we investigated the
function of OsSec18 in rice and found that OsSec18 complements the temperature
sensitive phenotype and interferes with vacuolar morphogenesis in yeast.
Overexpression of OsSec18 in rice decreased the plant height and 1000-grain
weight and altered the morphology of the protein bodies. Further examination
revealed that OsSec18 presented as a 290-kDa complex in rice endosperm cells.
Moreover, Os60sP0 was identified a component of this complex, demonstrating that
the OsSec18 complex contains another complex of P0(P1-P2)2 in rice endosperm
cells. Furthermore, we determined that the N-terminus of OsSec18 can interact
with the N- and C-termini of Os60sP0, whereas the C-terminus of OsSec18 can only
interact with the C-terminus of Os60sP0. CONCLUSION: Our results revealed that
the OsSec18 regulates vacuolar morphology in both yeast and rice endosperm cell
and the OsSec18 interacts with P0(P1-P2)2 complex in rice endosperm cell.
PMID- 25848692
TI - The economic impact of rapid Candida species identification by T2Candida among
high-risk patients.
AB - INTRODUCTION: This study estimates the cost-effectiveness and hospital budget
impact of rapid candidemia identification using T2Candida, a novel diagnostic
panel with same-day species-specific results. MATERIALS & METHODS: A 1-year
decision-tree model estimates hospital costs (2013 US$) and effects (candidemia
related deaths) for faster diagnostics versus blood culture (BC), accounting for
disease prevalence, distribution of Candida species, test characteristics
(sensitivity/specificity/time to result), antifungal medication and differential
length-of-stay and mortality by appropriate treatment timing. RESULTS: The model
estimates a hospital with 5100 annual high-risk patients could possibly save
$5,858,448 with T2Candida versus BC, a 47.6% decrease in candidemia diagnosis and
treatment budget ($1149/patient tested), while averting 60.6% of candidemia
related mortality. CONCLUSION: Hospitals may observe lower candidemia-related
inpatient costs and mortality with rapid Candida diagnosis.
PMID- 25848693
TI - Daring to Marry: Marriage Equality Activism After Proposition 8 as Challenge to
the Assimilationist/Radical Binary in Queer Studies.
AB - I analyze three case studies of marriage equality activism and marriage equality
based groups after the passage of Proposition 8 in California. Evaluating the
JoinTheImpact protests of 2008, the LGBTQ rights group GetEQUAL, and the group
One Struggle One Fight, I argue that these groups revise queer theoretical
arguments about marriage equality activism as by definition assimilationist,
homonormative, and single-issue. In contrast to such claims, the cases studied
here provide a snapshot of heterogeneous, intersectional, and coalition-based
social justice work in which creative methods of protest, including direct action
and flash mobs, are deployed in militant ways for marriage rights and beyond.
PMID- 25848694
TI - Saccharomyces cerevisiae cell wall components as tools for ochratoxin a
decontamination.
AB - The aim of this study was to evaluate the usefulness of Saccharomyces cerevisiae
cell wall preparations in the adsorption of ochratoxin A (OTA). The study
involved the use of a brewer's yeast cell wall devoid of protein substances,
glucans obtained by water and alkaline extraction, a glucan commercially
available as a dietary supplement for animals and, additionally, dried brewer's
yeast for comparison. Fourier Transform Infrared (FTIR) analysis of the obtained
preparations showed bands characteristic for glucans in the resulting spectra.
The yeast cell wall preparation, water-extracted glucan and the commercial glucan
bound the highest amount of ochratoxin A, above 55% of the initial concentration,
and the alkaline-extracted glucan adsorbed the lowest amount of this toxin. It
has been shown that adsorption is most effective at a close-to-neutral pH, while
being considerably limited in alkaline conditions.
PMID- 25848695
TI - Ras/MEK/MAPK-mediated regulation of heparin sulphate proteoglycans promotes
retinal fate in the Drosophila eye-antennal disc.
AB - Generating cellular heterogeneity is crucial to the development of complex
organs. Organ-fate selector genes and signalling pathways generate cellular
diversity by subdividing and patterning naive tissues to assign them regional
identities. The Drosophila eye-antennal imaginal disc is a well-characterised
system in which to study regional specification; it is first divided into
antennal and eye fates and subsequently retinal differentiation occurs within
only the eye field. During development, signalling pathways and selector genes
compete with and mutually antagonise each other to subdivide the tissue. Wingless
(Wg) signalling is the main inhibitor of retinal differentiation; it does so by
promoting antennal/head-fate via selector factors and by antagonising Hedgehog
(Hh), the principal differentiation-initiating signal. Wg signalling must be
suppressed by JAK/STAT at the disc posterior in order to initiate retinal
differentiation. Ras/MEK/MAPK signalling has also been implicated in initiating
retinal differentiation but its mode of action is not known. We find that
compromising Ras/MEK/MAPK signalling in the early larval disc results in expanded
antennal/head cuticle at the expense of the compound eye. These phenotypes
correspond both to perturbations in selector factor expression, and to de
repressed wg. Indeed, STAT activity is reduced due to decreased mobility of the
ligand Unpaired (Upd) along with a corresponding loss in Dally-like protein
(Dlp), a heparan sulphate proteoglycan (HSPG) that aids Upd diffusion.
Strikingly, blocking HSPG biogenesis phenocopies compromised Ras/MEK/MAPK, while
restoring HSPG expression rescues the adult phenotype significantly. This study
identifies a novel mode by which the Ras/MEK/MAPK pathway regulates regional-fate
specification via HSPGs during development.
PMID- 25848696
TI - ATP4a is required for development and function of the Xenopus mucociliary
epidermis - a potential model to study proton pump inhibitor-associated
pneumonia.
AB - Proton pump inhibitors (PPIs), which target gastric H(+)/K(+)ATPase (ATP4), are
among the most commonly prescribed drugs. PPIs are used to treat ulcers and as a
preventative measure against gastroesophageal reflux disease in hospitalized
patients. PPI treatment correlates with an increased risk for airway infections,
i.e. community- and hospital-acquired pneumonia. The cause for this correlation,
however, remains elusive. The Xenopus embryonic epidermis is increasingly being
used as a model to study airway-like mucociliary epithelia. Here we use this
model to address how ATP4 inhibition may affect epithelial function in human
airways. We demonstrate that atp4a knockdown interfered with the generation of
cilia-driven extracellular fluid flow. ATP4a and canonical Wnt signaling were
required in the epidermis for expression of foxj1, a transcriptional regulator of
motile ciliogenesis. The ATP4/Wnt module activated foxj1 downstream of ciliated
cell fate specification. In multiciliated cells (MCCs) of the epidermis, ATP4a
was also necessary for normal myb expression, apical actin formation, basal body
docking and alignment of basal bodies. Furthermore, ATP4-dependent Wnt/beta
catenin signaling in the epidermis was a prerequisite for foxa1-mediated
specification of small secretory cells (SSCs). SSCs release serotonin and other
substances into the medium, and thereby regulate ciliary beating in MCCs and
protect the epithelium against infection. Pharmacological inhibition of ATP4 in
the mature mucociliary epithelium also caused a loss of MCCs and led to impaired
mucociliary clearance. These data strongly suggest that PPI-associated pneumonia
in human patients might, at least in part, be linked to dysfunction of
mucociliary epithelia of the airways.
PMID- 25848698
TI - The impact of hepatitis B virus (HBV) infection on clinical outcomes of patients
with diffuse large B-cell lymphoma.
AB - We performed a retrospective study to analyse the characteristics and clinical
outcomes of diffuse large B-cell lymphoma (DLBCL) patients with hepatitis B virus
(HBV) infection and compare with those without HBV infection. The occurrence of
hepatitis after withdrawal of prophylactic antiviral treatment on completion of
chemotherapy was also assessed. The HBsAg-positive patients were given
prophylactic antiviral treatment until 6 months after finishing chemotherapy. A
total of 81 patients were recruited with 16 in the HBsAg-positive group and 65 in
the HBsAg-negative group. The clinical characteristics were similar in both
groups of patients. There was no significant difference in complete remission
rate between the two groups (63% in HBsAg-positive group vs. 54% in HBsAg
negative group, P = 0.59). There was also no statistically significant difference
in overall survival between the two groups (P = 0.23). Four of the 16 HBsAg
positive patients (25%) had hepatitis after cessation of chemotherapy and
prophylactic lamivudine. The mean time of onset of hepatitis was 3 months after
stopping lamivudine. In conclusion, HBV infection did not appear to affect the
prognosis of DLBCL patients given antiviral prophylaxis. It is reasonable to
consider prophylactic antiviral therapy to extend to at least one year on
completion of chemotherapy.
PMID- 25848697
TI - Distinct structural requirements for CDON and BOC in the promotion of Hedgehog
signaling.
AB - Proper levels of Hedgehog (HH) signaling are essential during embryonic
development and adult tissue homeostasis. A central mechanism to control HH
pathway activity is through the regulation of secreted HH ligands at the plasma
membrane. Recent studies have revealed a collective requirement for the cell
surface co-receptors GAS1, CDON and BOC in HH signal transduction. Despite their
requirement in HH pathway function, the mechanisms by which these proteins act to
promote HH signaling remain poorly understood. Here we focus on the function of
the two structurally related co-receptors, CDON and BOC. We utilized an in vivo
gain-of-function approach in the developing chicken spinal cord to dissect the
structural requirements for CDON and BOC function in HH signal transduction.
Notably, we find that although CDON and BOC display functional redundancy during
HH-dependent ventral neural patterning, these molecules utilize distinct
molecular mechanisms to execute their HH-promoting effects. Specifically, we
define distinct membrane attachment requirements for CDON and BOC function in HH
signal transduction. Further, we identify novel and separate extracellular motifs
in CDON and BOC that are required to promote HH signaling. Together, these data
suggest that HH co-receptors employ distinct mechanisms to mediate HH pathway
activity.
PMID- 25848699
TI - Awareness, treatment and control of cardiometabolic disorders in Chinese adults
with diabetes: a national representative population study.
AB - BACKGROUND: The diagnosis of diabetes has important clinic implications for the
prevention and management of cardiometabolic disorders. We aimed to investigate
the awareness, treatment and control of hypertension and dyslipidemia in
previously-diagnosed and newly-diagnosed diabetes in Chinese adult population.
METHODS: We conducted a cross-sectional survey in a nationally representative
sample of 98658 Chinese adults aged 18 years or older in 2010, using a complex,
multistage, probability sampling design. Glycemic status were defined according
to the 2010 American Diabetes Association criteria. Hypertension was diagnosed by
the Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure. Dyslipidemia was diagnosed by
the 2004 National Cholesterol Education Program Adult Treatment Panel III.
RESULTS: The weighted prevalence of hypertension and dyslipidemia gradually
increased in adults with normal glucose regulation, prediabetes, newly-diagnosed
diabetes and previously-diagnosed diabetes. Compared to newly-diagnosed diabetes
patients, previously-diagnosed diabetes patients were more likely to be aware of
hypertension (weighted percentage [95% confidence interval]: 55.2% [52.9%-57.5%]
vs 37.6% [35.9%-39.3%]) and dyslipidemia (33.9% [31.8%-36.1%] vs 12.8% [11.7%
13.9%]), to receive blood pressure-lowing (43.7% [41.5%-46.0%] vs 27.5% [26.0%
29.0%]) and lipid-lowering (18.9% [17.2%-20.7%] vs 5.4% [4.6%-6.2%]) therapies,
and to have controlled blood pressure (4.7% [3.5%-6.2%] vs 3.5% [2.6%-4.8%]) and
lipid (15.9% [12.3%-20.3%] vs 9.5% [6.4%-13.8%]) levels. CONCLUSIONS: Detection
and control of hypertension and dyslipidemia is far from optimal in Chinese
adults, especially in newly-diagnosed diabetes. Improved screening for diabetes
is required to promote a better prevention, treatment and control of hypertension
and dyslipidemia in China.
PMID- 25848700
TI - In silico discovery and validation of potent small-molecule inhibitors targeting
the activation function 2 site of human oestrogen receptor alpha.
AB - INTRODUCTION: Current approaches to inhibit oestrogen receptor-alpha (ERalpha)
are focused on targeting its hormone-binding pocket and have limitations. Thus,
we propose that inhibitors that bind to a coactivator-binding pocket on ERalpha,
called activation function 2 (AF2), might overcome some of these limitations.
METHODS: In silico virtual screening was used to identify small-molecule ERalpha
AF2 inhibitors. These compounds were screened for inhibition of ERalpha
transcriptional activity using stably transfected T47D-KBluc cell line. A direct
physical interaction between the AF2 binders and the ERalpha protein was measured
using biolayer interferometry (BLI) and an ERalpha coactivator displacement
assay. Cell viability was assessed by MTS assay in ERalpha-positive MCF7 cells,
tamoxifen-resistant (TamR) cell lines TamR3 and TamR6, and ERalpha-negative MDA
MB-453 and HeLa cell lines. In addition, ERalpha inhibition in TamR cells and the
effect of compounds on mRNA and protein expression of oestrogen-dependent genes,
pS2, cathepsin D and cell division cycle 2 (CDC2) were determined. RESULTS:
Fifteen inhibitors from two chemical classes, derivatives of pyrazolidine-3,5
dione and carbohydrazide, were identified. In a series of in vitro assays, VPC
16230 of the carbohydrazide chemical class emerged as a lead ERalpha AF2
inhibitor that significantly downregulated ERalpha transcriptional activity (half
maximal inhibitory concentration = 5.81 MUM). By directly binding to the ERalpha
protein, as confirmed by BLI, VPC-16230 effectively displaced coactivator
peptides from the AF2 pocket, confirming its site-specific action. VPC-16230
selectively suppressed the growth of ERalpha-positive breast cancer cells.
Furthermore, it significantly inhibited ERalpha mediated transcription in TamR
cells. More importantly, it reduced mRNA and protein levels of pS2, cathepsin D
and CDC2, validating its ER-directed activity. CONCLUSION: We identified VPC
16230 as an ERalpha AF2-specific inhibitor that demonstrated promising
antiproliferative effects in breast cancer cell lines, including TamR cells. VPC
16230 reduced the expression of ERalpha-inducible genes, including CDC2, which is
involved in cell division. We anticipate that the application of ERalpha AF2
inhibitors will provide a novel approach that can act as a complementary
therapeutic to treat ERalpha-positive, tamoxifen-resistant and metastatic breast
cancers.
PMID- 25848701
TI - Individual and psychosocial mechanisms of adaptive functioning in parentally
bereaved children.
AB - The authors examined factors theorized to contribute to adaptive functioning in
56 parentally bereaved children (age 7-13) who had lost their caregiver within
the previous 6 months. Adaptive functioning, defined as falling below clinical
threshold levels on all measures of depression, posttraumatic stress, anxiety,
and internalizing/externalizing symptoms, characterized 57% of the sample. Linear
mixed modeling revealed that children in the adaptive functioning group had lower
mean scores on avoidant coping and higher mean scores on coping efficacy,
religiosity, parental positive reinforcement, and parental empathy. Findings
suggest that adaptive functioning following parental loss is related to both
child-intrinsic factors and child-extrinsic factors.
PMID- 25848702
TI - Ginger-Mechanism of action in chemotherapy-induced nausea and vomiting: A review.
AB - Despite advances in antiemetic therapy, chemotherapy-induced nausea and vomiting
(CINV) still poses a significant burden to patients undergoing chemotherapy.
Nausea, in particular, is still highly prevalent in this population. Ginger has
been traditionally used as a folk remedy for gastrointestinal complaints and has
been suggested as a viable adjuvant treatment for nausea and vomiting in the
cancer context. Substantial research has revealed ginger to possess properties
that could exert multiple beneficial effects on chemotherapy patients who
experience nausea and vomiting. Bioactive compounds within the rhizome of ginger,
particularly the gingerol and shogaol class of compounds, interact with several
pathways that are directly implicated in CINV in addition to pathways that could
play secondary roles by exacerbating symptoms. These properties include 5-HT3,
substance P, and acetylcholine receptor antagonism; antiinflammatory properties;
and modulation of cellular redox signaling, vasopressin release, gastrointestinal
motility, and gastric emptying rate. This review outlines these proposed
mechanisms by discussing the results of clinical, in vitro, and animal studies
both within the chemotherapy context and in other relevant fields. The evidence
presented in this review indicates that ginger possesses multiple properties that
could be beneficial in reducing CINV.
PMID- 25848703
TI - Acute effects of caffeine supplementation on cortical arousal, anxiety,
physiological response and marksmanship in close quarter combat.
AB - Previous studies have researched the ergogenic effect of caffeine in different
shooting actions, but none of them in a stressful combat action. This study aimed
to analyse the effect of a dose of 400 mg of caffeine monohydrate on the psycho
physiological response and marksmanship of soldiers in close quarter combat
(CQC). We analysed the heart rate, blood lactate concentration, cortical arousal,
state anxiety and marksmanship of 19 soldiers in the Spanish Army (38.9 +/- 4.1
years; 177.4 +/- 5.3 cm; 78.8 +/- 7.6 kg) before and after a CQC simulation in a
double-blind procedure. Caffeine intake did not improve shooting performance in
CQC; however, it increased cognitive and somatic anxiety levels. PRACTITIONER
SUMMARY: According to the previous literature, the ingestion of caffeine could
help soldiers in operations conducted in sleep deprivation conditions, but in
stressful combat situations it does not improve the marksmanship of soldiers.
PMID- 25848704
TI - Molecular mechanism and clinical impact of APOBEC3B-catalyzed mutagenesis in
breast cancer.
AB - Cancer genomic DNA sequences enable identification of all mutations and suggest
targets for precision medicine. The identities and patterns of the mutations
themselves also provide critical information for deducing the originating DNA
damaging agents, causal molecular mechanisms, and thus additional therapeutic
targets. A classic example is ultraviolet light, which crosslinks adjacent
pyrimidines and leads to C-to-T transitions. A new example is the DNA cytosine
deaminase APOBEC3B, which was identified recently as a source of DNA damage and
mutagenesis in breast, head/neck, cervix, bladder, lung, ovary, and to lesser
extents additional cancer types. This enzyme is normally an effector protein in
the innate immune response to virus infection but upregulation in these cancer
types causes elevated levels of genomic C-to-U deamination events, which manifest
as C-to-T transitions and C-to-G transversions within distinct DNA trinucleotide
contexts (preferentially 5'-TCA and 5'-TCG). Genomic C-to-U deamination events
within the same trinucleotide contexts also lead to cytosine mutation clusters
(kataegis), and may precipitate visible chromosomal aberrations such as
translocations. Clinical studies indicate that APOBEC3B upregulation correlates
with poorer outcomes for estrogen receptor-positive breast cancer patients,
including shorter durations of disease-free survival and overall survival after
surgery. APOBEC3B may therefore have both diagnostic and prognostic potential.
APOBEC3B may also be a candidate for therapeutic targeting because inhibition of
this non-essential enzyme is predicted to decrease tumor mutation rates and
diminish the likelihood of undesirable mutation-dependent outcomes such as
recurrence, metastasis, and the development of therapy resistant tumors.
PMID- 25848707
TI - Mitochondria fingerprint longevity in iPSCs.
PMID- 25848706
TI - From pills to patients: an evaluation of data sources to determine the number of
people living with HIV who are receiving antiretroviral therapy in Germany.
AB - BACKGROUND: This study aimed to determine the number of people living with HIV
receiving antiretroviral therapy (ART) between 2006 and 2013 in Germany by using
the available numbers of antiretroviral drug prescriptions and treatment data
from the ClinSurv HIV cohort (CSH). METHODS: The CSH is a multi-centre, open,
long-term observational cohort study with an average number of 10.400 patients in
the study period 2006-2013. ART has been documented on average for 86% of those
CSH patients and medication history is well documented in the CSH. RESULTS: The
proportion of CSH patients receiving TCMs increased continuously over time (from
85% to 93%; 2006-2013). In contrast, treatment interruptions declined remarkably
(from 11% to 2%; 2006-2013). The total number of HIV-infected people with ART
experience in Germany increased from 31,500 (95% CI 31,000-32,000) individuals to
54,000 (95% CI 53,000-55,500) over the observation period (including 16.3%
without SHI and persons who had interrupted ART). An average increase of
approximately 2,900 persons receiving ART was observed annually in Germany.
CONCLUSIONS: A substantial increase in the number of people receiving ART was
observed from 2006 to 2013 in Germany.
PMID- 25848705
TI - Sigma-1 receptor mediates acquisition of alcohol drinking and seeking behavior in
alcohol-preferring rats.
AB - Sigma-1 receptor (Sig-1R) has been proposed as a novel therapeutic target for
drug and alcohol addiction. We have shown previously that Sig-1R agonists
facilitate the reinforcing effects of ethanol and induce binge-like drinking,
while Sig-1R antagonists on the other hand block excessive drinking in genetic
and environmental models of alcoholism, without affecting intake in outbred non
dependent rats. Even though significant progress has been made in understanding
the function of Sig-1R in alcohol reinforcement, its role in the early and late
stage of alcohol addiction remains unclear. Administration of the selective Sig
1R antagonist BD-1063 dramatically reduced the acquisition of alcohol drinking
behavior as well as the preference for alcohol in genetically selected TSRI
Sardinian alcohol preferring (Scr:sP) rats; the treatment had instead no effect
on total fluid intake, food intake or body weight gain, proving selectivity of
action. Furthermore, BD-1063 dose-dependently decreased alcohol-seeking behavior
in rats trained under a second-order schedule of reinforcement, in which
responding is maintained by contingent presentation of a conditioned reinforcer.
Finally, an innate elevation in Sig-1R protein levels was found in the nucleus
accumbens of alcohol-preferring Scr:sP rats, compared to outbred Wistar rats,
alteration which was normalized by chronic, voluntary alcohol drinking. Taken
together these findings demonstrate that Sig-1R blockade reduces the propensity
to both acquire alcohol drinking and to seek alcohol, and point to the nucleus
accumbens as a potential key region for the effects observed. Our data suggest
that Sig-1R antagonists may have therapeutic potential in multiple stages of
alcohol addiction.
PMID- 25848708
TI - LNK1 and LNK2 recruitment to the evening element require morning expressed
circadian related MYB-like transcription factors.
AB - Transcriptional feedback loops in Arabidopsis circadian clock is composed of more
repressive components, while the knowledge of activation mechanism remains
limited. We recently reported 2 members from a family of NIGHT LIGHT-INDUCIBLE
AND CLOCK-REGULATED genes, LNK1 and LNK2, dynamically interact with morning
phased transcriptional factors, like CIRCADIAN CLOCK ASSOCIATED1 (CCA1), LATE
ELONGATED HYPOCOTYL (LHY), REVEILLE8 (RVE8) and RVE4, and function as
coactivators for the expression of TIMING OF CAB EXPRESSION1 (TOC1) and PSEUDO
RESPONSE REGULATOR5 (PRR5) via transcriptional factors RVE8 and RVE4. Here we
provide evidence that both LNK1 and LNK2 play critical role in the
transcriptional activation of PRR5, LNK1 may contribute more than LNK2 did under
experimental conditions. We also identified that both LNK1 and LNK2 recruitment
to the evening element of PRR5 promoter via LNK1-RVE8 or LNK2-RVE8 proteins
complex through electrophoretic mobility shift assay. Therefore LNK1 and LNK2
function as coactivator of dawn-phased MYB-like transcription factors, such as
RVE8 in morning complex to regulate the target genes expression.
PMID- 25848709
TI - Janus Suprabead Displays Derived from the Modified Photonic Crystals toward
Temperature Magnetism and Optics Multiple Responses.
AB - The design and development of Janus suprabeads (JSs) with multiple responses are
highly desirable in the fabrication of functional nanomaterials. In this work, we
report a triphase microfluidic strategy for the construction of JSs with
temperature-magnetism-optics triple responses. Initially, macromonomer
poly(methacrylic acid) (PMAA) obtained via catalytic chain transfer
polymerization (CCTP) was grafted onto the polystyrene (PS) colloidal photonic
crystals (CPCs) surface. Because abundant carboxylic acid groups in PMAA could
coordinate cadmium ions for in situ production of fluorescent CdS quantum dots
(QDs) after introducing sulfur ions, the as-prepared JSs were endowed with
favorable optical properties. Meanwhile, the as-prepared Cd(2+)/PS CPCs were
employed as a template to build JSs with temperature-magnetism sensitivity via
the introduction of magnetic Fe3O4 and hydrogels. Finally, the fluorescence
pattern was easily performed by using chalcogenides as "ink" to write on the pad,
in which in situ reaction mechanism was involved in the response. The multiple
responsive JSs show promising applications in sensor, display, and
anticounterfeit fields.
PMID- 25848710
TI - Pt(II) metal complexes tailored with a newly designed spiro-arranged tetradentate
ligand; harnessing of charge-transfer phosphorescence and fabrication of sky blue
and white OLEDs.
AB - Tetradentate bis(pyridyl azolate) chelates are assembled by connecting two
bidentate 3-trifluoromethyl-5-(2-pyridyl)azoles at the six position of pyridyl
fragment with the tailored spiro-arranged fluorene and/or acridine
functionalities. These new chelates were then utilized in synthesizing a series
of Pt(II) metal complexes [Pt(Ln)], n = 1-5, from respective chelates L1-L5 and
[PtCl2(DMSO)2] in 1,2-dimethoxyethane. The single-crystal X-ray structural
analyses were executed on 1, 3, and 5 to reveal the generalized structures and
packing arrangement in crystal lattices. Their photophysical properties were
measured in both solution and solid state and are discussed in the context of
computational analysis. These L1-L5 coordinated Pt(II) species exhibit intense
emission, among which complex 5 shows remarkable solvatochromic phosphorescence
due to the dominant intraligand charge transfer transition induced by the new
bis(pyridyl azolate) chelates. Moreover, because of the higher-lying highest
occupied molecular orbital of acridine, complex 5 can be considered as a novel
bipolar phosphor. Successful fabrication of blue and white organic light-emitting
diodes (OLEDs) using Pt(II) complexes 3 and 5 as the phosphorescent dopants are
reported. In particular, blue OLEDs with 5 demonstrated peak efficiencies of
15.3% (36.3 cd/A, 38.0 lm/W), and CIE values of (0.190, 0.342) in a double
emitting layer structure. Furthermore, a red-emitting Os(II) complex and 5 were
used to fabricate warm-white OLEDs to achieve peak external quantum efficiency,
luminance efficiency, and power efficiency values as high as 12.7%, 22.5 cd/A,
and 22.1 lm/W, respectively.
PMID- 25848711
TI - Laparoscopic Transabdominal With Transdiaphragmatic Access Improves Resection of
Difficult Posterosuperior Liver Lesions.
AB - OBJECTIVE: We describe the technical details and evaluate the safety,
feasibility, and usefulness of a combined lateral and abdominal (CLA) approach
for laparoscopic resection of liver segments 7 and 8. BACKGROUND: Laparoscopic
resection of lesions in the posterosuperior area of segments 7 and 8 is
technically challenging, and currently there is no standardized laparoscopic
approach. METHODS: Through review of a prospectively maintained database, we
identified 44 patients who underwent laparoscopic resection of lesions in segment
7 or 8. Twenty-five patients required the CLA approach because their lesions were
more posterosuperior and intraparenchymal; 19 patients underwent resection with a
regular abdominal-only approach of more accessible anteroinferior lesions. We
reviewed operative details and video footage of these operations and compared the
outcomes of the 2 groups. RESULTS: In the group treated with the CLA approach,
deep location was more frequent (88% vs 42%; P = 0.035), median tumor diameter
was larger (24.5 mm vs 15 mm; P = 0.114), and the median weight of the excised
parenchyma was greater (56.5 g vs 23 g; P = 0.093). Median operative time was
longer in the CLA approach group (217.5 minutes vs 165 minutes; P = 0.046), but
blood loss, rate of conversion to open surgery, surgical margin status,
morbidity, and mortality were similar between the 2 groups. CONCLUSIONS: The CLA
approach permits safe laparoscopic resection of lesions in the posterosuperior
area of segments 7 and 8, allowing surgeons to overcome the difficulties of
limited visualization and access to the target lesions.
PMID- 25848712
TI - Moving from strategy to implementation... first steps.
PMID- 25848714
TI - Evolution of thoracic surgery in Canada.
AB - BACKGROUND: Canada's contributions toward the 21st century's practice of thoracic
surgery have been both unique and multilayered. Scattered throughout are tales of
pioneers where none had gone before, where opportunities were greeted by
creativity and where iconic figures followed one another. OBJECTIVE: To describe
the numerous and important achievements of Canadian thoracic surgeons in the
areas of surgery for pulmonary tuberculosis, thoracic oncology, airway surgery
and lung transplantation. METHOD: Information was collected through reading of
the numerous publications written by Canadian thoracic surgeons over the past 100
years, interviews with interested people from all thoracic surgery divisions
across Canada and review of pertinent material form the archives of several
Canadian hospitals and universities. RESULTS: Many of the developments occurred
by chance. It was the early and specific focus on thoracic surgery, to the
exclusion of cardiac and general surgery, that distinguishes the Canadian
experience, a model that is now emerging everywhere. From lung transplantation in
chimera twin calves to ex vivo organ preservation, from the removal of airways to
tissue regeneration, and from intensive care research to complex science,
Canadians have excelled in their commitment to research. Over the years, the
influence of Canadian thoracic surgery on international practice has been
significant. CONCLUSIONS: Canada spearheaded the development of thoracic surgery
over the past 100 years to a greater degree than any other country. From research
to education, from national infrastructures to the regionalization of local
practices, it happened in Canada.
PMID- 25848715
TI - Effective handover communication: Do we need more evidence?
PMID- 25848716
TI - Partially thrombosed multiple pulmonary artery aneurysm secondary to Behcet
disease.
PMID- 25848717
TI - A severe complication of crack cocaine use.
AB - The present report describes a 48-year-old woman with a history of recurrent
'crack' cocaine use, who developed progressive shortness of breath over a period
of years. Serial imaging revealed progressive interstitial fibrosis secondary to
recurrent alveolar hemorrhage and inflammation from crack cocaine. The present
case serves as a reminder of the numerous sequelae of crack cocaine use,
highlighting one particularly severe outcome.
PMID- 25848719
TI - E-cigarette use in patients receiving home oxygen therapy.
AB - Current smokers who are prescribed home oxygen may not benefit from the therapy.
In addition to being an obvious fire hazard, there is some evidence that the
physiological mechanisms by which home oxygen is believed to operate are
inhibited by smoking. Although their effectiveness is yet to be demonstrated,
electronic cigarettes (e-cigarettes) are often regarded as an aid to smoking
cessation. However, several burn accidents in e-cigarette smokers receiving home
oxygen therapy have also been reported, leading Health Canada to release a
warning of fire risk to oxygen therapy patients from e-cigarettes. It is the
authors' position that patients receiving oxygen should definitely not use e
cigarettes. The authors provide suggestions for addressing the delicate issue of
home oxygen therapy in current cigarette and/or e-cigarette smokers.
PMID- 25848720
TI - How long does it take to initiate a child on long-term invasive ventilation?
Results from a Canadian pediatric home ventilation program.
AB - OBJECTIVE: To assess the length of stay required to initiate long-term invasive
ventilation at the authors' institution, which would inform future interventional
strategies to streamline the in-hospital stay for these families. METHODS: A
retrospective chart review of children initiated on invasive long-term
ventilation via tracheostomy at the authors' acute care centre between January
2005 and December 2013 was performed. RESULTS: Thirty-five children were
initiated on long-term invasive ventilation via tracheostomy at the acute care
hospital; 19 (54%) were male. The median age at time of admission was 0.52 years
(interquartile range [IQR] 0.06 to 9.58 years) . Musculoskeletal disease (n=11
[31%]) was the most common reason for tracheostomy insertion. Two children died
during the hospital admission. Fifteen children were discharged home directly
from the acute care hospital and 18 were moved to the rehabilitation hospital.
Six are current inpatients of the rehabilitation centre and were never discharged
home. Combining the length of stay at the acute care and rehabilitation hospitals
for the entire cohort, the median length of stay was 162.0 days (IQR 98.0 to
275.0 days) and 97.0 days (IQR 69.0 to 210.0 days), respectively, from the time
of tracheostomy insertion. CONCLUSIONS: The median length of stay from the
initiation of invasive long-term ventilation to discharge home from the
rehabilitation hospital was somewhat long compared with other ventilation
programs worldwide. Additionally, approximately 20% of the cohort never
transitioned home. There is a timely need to benchmark across the country and
internationally, to identify and implement strategies for cohesive, coordinated
care for these children to decrease overall length of stay.
PMID- 25848721
TI - Jump-Squat Performance and Its Relationship With Relative Training Intensity in
High-Level Athletes.
AB - PURPOSE: To examine the relationship between the relative load in full squats and
the height achieved in jump-squat (JS) exercises and to determine the load that
maximizes the power output of high-level athletes. METHOD: Fifty-one male high
level track-and-field athletes (age 25.2 +/- 4.4 y, weight 77. +/- 6.2 kg, height
179.9 +/- 5.6 cm) who competed in sprinting and jumping events took part in the
study. Full-squat 1-repetition-maximum (1-RM) and JS height (JH) with loads from
17 to 97 kg were measured in 2 sessions separated by 48 h. RESULTS: Individual
regression analyses showed that JH (R2 = .992 +/- .005) and the jump decrease
(JD) that each load produced with respect to the unloaded countermovement jump
(CMJ) (R2 = .992 +/- 0.007) are highly correlated with the full-squat %1-RM,
which means that training intensities can be prescribed using JH and JD values.
The authors also found that the load that maximizes JS's power output was 0%RM
(ie, unloaded CMJ). CONCLUSIONS: These results highlight the close relationship
between JS performance and relative training intensity in terms of %1-RM. The
authors also observed that the load that maximizes power output was 0%1-RM.
Monitoring jump height during JS training could help coaches and athletes
determine and optimize their training loads.
PMID- 25848722
TI - Sequential one-pot multienzyme (OPME) synthesis of lacto-N-neotetraose and its
sialyl and fucosyl derivatives.
AB - Lacto-N-neotetraose and its sialyl and fucosyl derivatives including Lewis x
(Le(x)) pentasaccharide, sialyl Lewis x (sLe(x)) hexasaccharide and internally
sialylated derivatives were enzymatically synthesized from readily available
lactoside, commercially available uridine 5'-diphosphate-glucose (UDP-Glc) and
the corresponding monosaccharides using a highly efficient sequential one-pot
multienzyme (OPME) strategy. The OPME strategy which combines bacterial
glycosyltransferases and sugar nucleotide generation enzymes provides easy access
to the biologically important complex oligosaccharides at preparative scale.
Moreover, the same OPME strategy can be used for the regioselective introduction
of sialic acid to the internal galactose unit of LNnT in a designed glycosylation
route by simply changing the glycosylation sequence.
PMID- 25848723
TI - Lectin RCA-I specifically binds to metastasis-associated cell surface glycans in
triple-negative breast cancer.
AB - INTRODUCTION: Triple-negative breast cancer (TNBC) patients often face a high
risk of early relapse characterized by extensive metastasis. Previous works have
shown that aberrant cell surface glycosylation is associated with cancer
metastasis, suggesting that altered glycosylations might serve as diagnostic
signatures of metastatic potential. To address this question, we took TNBC as an
example and analyzed six TNBC cell lines, derived from a common progenitor, that
differ in metastatic potential. METHODS: We used a microarray with 91 lectins to
screen for altered lectin bindings to the six TNBC cell lines. Candidate lectins
were then verified by lectin-based flow cytometry and immunofluorescent staining
assays using both TNBC/non-TNBC cancer cells. Patient-derived tissue microarrays
were then employed to analyze whether the staining of Ricinus communis agglutinin
I (RCA-I), correlated with TNBC severity. We also carried out real-time cell
motility assays in the presence of RCA-I. Finally, liquid chromatography-mass
spectrometry/tandem spectrometry (LC-MS/MS) was employed to identify the membrane
glycoproteins recognized by RCA-I. RESULTS: Using the lectin microarray, we found
that the bindings of RCA-I to TNBC cells are proportional to their metastatic
capacity. Tissue microarray experiments showed that the intensity of RCA-I
staining is positively correlated with the TNM grades. The real-time cell
motility assays clearly demonstrated RCA-I inhibition of adhesion, migration, and
invasion of TNBC cells of high metastatic capacity. Additionally, a membrane
glycoprotein, POTE ankyrin domain family member F (POTEF), with different
galactosylation extents in high/low metastatic TNBC cells was identified by LC
MS/MS as a binder of RCA-I. CONCLUSIONS: We discovered RCA-I, which bound to TNBC
cells to a degree that is proportional to their metastatic capacities, and found
that this binding inhibits the cell invasion, migration, and adhesion, and
identified a membrane protein, POTEF, which may play a key role in mediating
these effects. These results thus indicate that RCA-I-specific cell surface
glycoproteins may play a critical role in TNBC metastasis and that the extent of
RCA-I cell binding could be used in diagnosis to predict the likelihood of
developing metastases in TNBC patients.
PMID- 25848724
TI - Designing of dynamic polyethyleneimine (PEI) brushes on polyurethane (PU)
ureteral stents to prevent infections.
AB - Permanent antibacterial coatings have been developed by brush-like
polyethyleneimine (PEI) on polyurethane (PU) ureteral stents since bacterial
adhesion and biofilm formation with the following encrustation on stent surface
limit their long term usage. In order to control or prevent bacterial infections;
PEI chains with two different molecular weights (Mn: 1800 or 60,000 Da) were
covalently attached on the polyurethane (PU) surface by "grafting to" approach to
obtain a brush-like structure. Then, PEI brushes were alkylated with bromohexane
to enhance the disruption of bacterial membranes with increasing polycationic
character. X-ray Photoelectron and Infrared Spectroscopy investigations confirmed
that PEI grafting and alkylation steps were performed successfully. Surface
roughness in dry state increased dramatically from 65.8 nm to 277.7 nm and 145.2
nm for short chain PEI and long chain PEI grafted samples, respectively. Both low
and high molecular weight PEI grafts exhibited a brush-like structure and potent
antibacterial activity by lowering the adherence of Klebsiella pneumonia,
Escherichia coli and Proteus mirabilis species up to two orders of magnitude
without any cytotoxic effect on L929 and G/G cells. Thus, permanent bactericidal
activity was achieved by the contact-active strategy of dynamic PEI brush-like
structures on polyurethane ureteral stent.
PMID- 25848726
TI - Surface-enhanced Raman scattering (SERS)-active gold nanochains for multiplex
detection and photodynamic therapy of cancer.
AB - Multifunctional nanomedicine holds considerable promise as the next generation of
medicine that will enable early detection of diseases, as well as simultaneous
monitoring and therapy with minimal toxicity. In particular, surface-enhanced
Raman scattering (SERS) technology with high sensitivity and multiplexing
capabilities is emerging as a powerful alternative for identifying specific
biological targets in live cells. In this paper, we present the synthesis of SERS
active gold nanochains (AuNCs) as a potential theranostic system for multiplex
detection and photodynamic therapy (PDT) of cancer. AuNCs were prepared by a
simple physical mixing method to assemble citrate-stabilized gold nanoparticles
into nanochains using hyaluronic acid and hydrocaffeic acid (HA-HCA) conjugates
as templates. In addition, Raman reporters and photosensitizers (PSs) were
conjugated onto the surface of the AuNCs for multiplex detection and PDT action.
After mixing with HA-HCA conjugates, citrate-stabilized gold nanoparticles formed
the AuNC structure, and AuNC length was controlled by the HCA conjugation ratio
in the HA-HCA conjugates. AuNCs exhibited maximal absorption in the near-infrared
(NIR) spectral region and effective SERS property. Confocal microscopy, flow
cytometry, Raman spectroscopy and Bio-TEM measurements were used to determine
cellular uptake of the Raman reporter, PS and AuNCs in HeLa cells. AuNCs
conjugated with Raman reporter and PS (HA-HCAn-Au-Pheo-NPT) showed more than 99%
cellular uptake and exhibited excellent phototoxicity even at low PS
concentrations compared with free PS after laser irradiation. This SERS-active
AuNC (HA-HCAn-Au-Pheo-NPT) shows promise for applications in theranostics,
integrating SERS imaging and PDT.
PMID- 25848725
TI - Probing carbonate in bone forming minerals on the nanometre scale.
AB - To devise new strategies to treat bone disease in an ageing society, a more
detailed characterisation of the process by which bone mineralises is needed. In
vitro studies have suggested that carbonated mineral might be a precursor for
deposition of bone apatite. Increased carbonate content in bone may also have
significant implications in altering the mechanical properties, for example in
diseased bone. However, information about the chemistry and coordination
environment of bone mineral, and their spatial distribution within healthy and
diseased tissues, is lacking. Spatially resolved analytical transmission electron
microscopy is the only method available to probe this information at the length
scale of the collagen fibrils in bone. In this study, scanning transmission
electron microscopy combined with electron energy-loss spectroscopy (STEM-EELS)
was used to differentiate between calcium-containing biominerals (hydroxyapatite,
carbonated hydroxyapatite, beta-tricalcium phosphate and calcite). A carbon K
edge peak at 290 eV is a direct marker of the presence of carbonate. We found
that the oxygen K-edge structure changed most significantly between minerals
allowing discrimination between calcium phosphates and calcium carbonates. The
presence of carbonate in carbonated HA (CHA) was confirmed by the formation of
peak at 533 eV in the oxygen K-edge. These observations were confirmed by
simulations using density functional theory. Finally, we show that this method
can be utilised to map carbonate from the crystallites in bone. We propose that
our calibration library of EELS spectra could be extended to provide spatially
resolved information about the coordination environment within bioceramic
implants to stimulate the development of structural biomaterials.
PMID- 25848727
TI - Bone response to a novel Ti-Ta-Nb-Zr alloy.
AB - Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material
for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti-6Al
4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the
material of choice for high-load applications. There is a call for the
development of new alloys, not only to eliminate the potential toxic effect of Al
and V but also to meet the challenges imposed on dental and maxillofacial
reconstructive devices, for example. The present work evaluates a novel, dual
stage, acid-etched, Ti-Ta-Nb-Zr alloy implant, consisting of elements that create
low toxicity, with the potential to promote osseointegration in vivo. The alloy
implants (denoted Ti-Ta-Nb-Zr) were evaluated after 7 days and 28 days in a rat
tibia model, with reference to commercially pure titanium grade 4 (denoted Ti).
Analyses were performed with respect to removal torque, histomorphometry and gene
expression. The Ti-Ta-Nb-Zr showed a significant increase in implant stability
over time in contrast to the Ti. Further, the histological and gene expression
analyses suggested faster healing around the Ti-Ta-Nb-Zr, as judged by the
enhanced remodeling, and mineralization, of the early-formed woven bone and the
multiple positive correlations between genes denoting inflammation, bone
formation and remodeling. Based on the present experiments, it is concluded that
the Ti-Ta-Nb-Zr alloy becomes osseointegrated to at least a similar degree to
that of pure titanium implants. This alloy is therefore emerging as a novel
implant material for clinical evaluation.
PMID- 25848728
TI - beta,gamma-Bis-substituted PNA with configurational and conformational switch:
preferred binding to cDNA/RNA and cell-uptake studies.
AB - (S,S)- and (R,R)-beta,gamma-Bis-substituted PNAs were synthesized from the C-2
symmetric vicinal diamine system embedded in 1,4 dihydroxybutane and 1,4
dimethoxybutane scaffolds. (R,R)-beta,gamma-Bis-methoxymethyl-PNA derived from d
tartaric acid was found to be in the right configuration and conformation to be
an excellent mimic of PNA, endowed with superior ability to enter into cells.
PMID- 25848729
TI - Engineered water-soluble two-dimensional magnetic nanocomposites: towards highly
magnetic relaxometric properties.
AB - Water dispersible two-dimensional magnetic nanocomposites are formed by phase
transferring hydrophobic manganese-doped ferrite nanoparticles (MFPs) into
aqueous solvent using a one-step simple approach involving only graphene oxide
(GO) as the phase transfer agent. The resultant hydrophilic magnetic
nanocomposites (MFNs) are surprisingly stable in the aqueous phase despite its
large hydrodynamic size (dhyd). Because of its unique construct that promotes
water accessibility towards the MFP core, large MFNs loaded with an 18 nm MFP
core (MFN-18; dhyd = 577.9 nm) exhibits transverse relaxivity (r2) up to ~6.8
times (r2 = 800.8 mM [Mn + Fe](-1) s(-1)) higher than the typical individually
coated MFP-18 with amphiphilic brush copolymers (r2 = 117.3 mM [Mn + Fe](-1) s(
1)). Meanwhile, the overall nanocomposites dhyd can be further reduced by
employing a smaller pre-sonicated GO sheet phase transfer agent. As a result of
using small GO sheets with enhanced hydrophilicity, the r2 of small MFN-18*
nanocomposites (dhyd = 224.9 nm) increases by approximately 37% (r2 = 1097.4 mM
[Mn + Fe](-1) s(-1)) as compared to larger MFN-18. From a simple comparative
study among various magnetic nanocomposites involving a MFP-18 core, the high MFN
18 r2 relaxivity value can be attributed to enhanced water diffusion and exchange
due to the GO sheet, allowing better interaction between magnetic the MFP core
and water protons. The proposed method can be readily extended to convert other
types of hydrophobic nanoparticles into water-dispersible nanocomposites.
PMID- 25848730
TI - Disentangling vibronic and solvent broadening effects in the absorption spectra
of coumarin derivatives for dye sensitized solar cells.
AB - We simulate from first-principles the absorption spectra of five structure
related coumarin derivatives utilized in dye sensitized solar cells (DSSCs),
investigating the vibronic and solvent contributions to the position and width of
the spectra in ethanol. Ground and excited state potential energy surfaces (PESs)
are modeled by Density Functional Theory (DFT) and its time-dependent (TD)
expression for the excited state (TD-DFT). The solute vibronic structure
associated with the spectrum is calculated by a TD formalism, accounting for both
Duschinsky and temperature effects, while solvent inhomogeneous broadening is
evaluated according to Marcus' theory, computing the solvent reorganization
energy by the state-specific implementation of the polarizable continuum model
(PCM) within TD-DFT. We adopted both the standard hybrid PBE0 and the range
separated CAM-B3LYP functionals showing that the latter performs better both
concerning the vibronic and solvent-induced contributions to the absorption
lineshape. The different predictions of the two functionals are then rationalized
in terms of the charge transfer (CT) character of the transitions showing that,
in this class of compounds, it is strongly dependent on the nuclear structure.
Such a dependence introduces a bias in the PBE0 PES that has a drastic impact on
the vibronic spectra. We show that both the intrinsic vibronic structure and the
solvent broadening play a relevant role in differentiating the absorption width
of the five dyes. In this sense, our results provide a guide to understand the
sources of spectral broadening of this family of dyes, a valuable help for a
rational design of new molecules to improve DSSC devices.
PMID- 25848731
TI - Communicating public health messages.
PMID- 25848732
TI - Reflections on a 38-year career in public health advocacy: 10 pieces of advice to
early career researchers and advocates.
AB - There are many important principles and lessons that public health researchers
and advocates who hope to influence policy and practice need to consider. In this
paper, I set out what I consider to be 10 of the most fundamental of these.
Together, these focus on the importance of preserving public confidence in the
evidence base underscoring public policy; being clear and concrete about the
policy reforms you support; emphasising the values on which policy is based;
understanding the structure, conventions and subtextual features of news
reporting; developing 'killer facts' with 'earworm' potential; appreciating that
the advocacy process leading to policy change almost always takes a long time;
and growing a rhinoceros hide to assist in the inevitable attacks you will face.
PMID- 25848733
TI - Should we do battle with antivaccination activists?
AB - Antivaccination activists have existed since variolation was introduced in Europe
in the 18th century. Today, they continue to attempt to influence the vaccination
decisions of parents. Commentators have expressed concern about the impact of
such activists on vaccination rates and disease outbreaks. Some argue that public
health advocates should engage in adversarial approaches involving public
attempts to discredit or stop an antivaccination group or individual. This
article argues that such adversarial advocacy may not be the most effective way
to support vaccine programs. It argues this on the basis of what is known to
influence vaccination attitudes and uptake, and the unintended negative
consequences that can arise from an adversarial approach. These include drawing
attention to such activists and their arguments, and potentially alienating the
most important audience - hesitant parents - where the primary goal is to
establish trust. The exception is when the antivaccination activists' actions may
cause direct harm, such as encouraging a 'disease party' or illegal activities.
Generally, however, advocacy should focus on areas where real gains can be made -
on policies that directly address determinants of low coverage such as lack of
opportunity to vaccinate and lack of acceptance of vaccination. This includes
advocacy for accessible and affordable vaccines. In addressing the global problem
of vaccine hesitancy, public health has a responsibility to better monitor public
attitudes, support health professionals in communication, and develop and test
strategies that engage vaccine-hesitant parents and communities.
PMID- 25848734
TI - Fetal alcohol spectrum disorders in Australia--the future is prevention.
AB - Fetal alcohol spectrum disorders (FASD) are increasingly recognised throughout
Australia as important, but preventable, disorders that result in lifelong
problems with health and learning, mental health, behaviour and substance misuse.
The role of this article is to highlight current efforts, which are in their
infancy, to recognise and prevent FASD in Australia. A federal parliamentary
inquiry into FASD (2011), development of an Australian Government 'action plan'
to prevent FASD (2013) and the announcement in June 2014 of government funding to
progress the plan and appoint a National FASD Technical Network have focused
attention on the need for FASD prevention in Australia. Other welcome
developments include the formation of Parliamentarians for the Prevention of FASD
(2011), revision of guidelines regarding alcohol use in pregnancy by the National
Health and Medical Research Council (NHMRC; 2009) and provision of targeted
funding for FASD research by the NHMRC (2013). Initiatives by Indigenous
communities to restrict access to alcohol and diagnose and prevent FASD have had
a significant impact in high-risk communities. The National Organisation for FASD
has an important ongoing advocacy and educational remit. Nongovernment
organisations such as the Foundation for Alcohol Research and Education have
contributed to prevention by developing resources to assist health professionals
to advise women about the harms of alcohol use in pregnancy; encouraging men to
abstain from alcohol during the pregnancy; drafting a national plan; and
advocating for pregnancy warning labels on alcohol. Internationally, in 2014, a
charter on prevention of FASD was published in The Lancet Global Health, and the
World Health Organization released guidelines for identification and management
of substance use in pregnancy. Early recognition and support for individuals with
FASD is crucial to prevent adverse secondary outcomes; however, primary
prevention of alcohol use in pregnancy, and hence FASD, should be our future
goal. The causal pathway to drinking in pregnancy is complex and requires a broad
social ecological approach. Prevention will take time, must involve all
government sectors and should incorporate primary, secondary and tertiary
strategies to target both the broader community and populations at high risk of
alcohol use during pregnancy.
PMID- 25848735
TI - Social media campaigns that make a difference: what can public health learn from
the corporate sector and other social change marketers?
AB - AIM: A great deal of enthusiasm and interest exists in using social media for
public health communications, but few research studies have examined its success
in promoting and adopting protective health behaviours. To begin to understand
how best to develop effective online social marketing campaigns, this paper
provides a summary of success factors and key lessons learnt from selected social
media campaign case studies. STUDY TYPE: Case study review Methods: A selection
of case studies was reviewed for lessons in campaign development, delivery and
evaluation from both the corporate and public health sectors. Information about
the objective of the campaign, the tactics used and the lessons learnt was
extracted from each case study. Lessons learnt from across the case studies were
then sorted according to themes. RESULTS: Lessons from the nine case studies
selected were categorised into eight themes: planning, use of social media tools,
community, content, personal benefits, promotion, costs and challenges. Outcome
evaluation data were lacking in the case studies. CONCLUSIONS: Overall, the nine
case studies show that social media hold promise in changing user behaviours and
that social media are highly effective in recruiting participants and motivating
them to take small, concrete actions. The case studies also demonstrate that
there is room in social media for targeted, inexpensive, small-scale projects, as
well as large, well-funded, mass-reach marketing blitzes. Social media campaign
process and impact evaluation measures are readily available. Outcome evaluation
models and measures are needed to better assess the effectiveness of social media
campaigns in changing health behaviours.
PMID- 25848736
TI - Manual versus automated coding of free-text self-reported medication data in the
45 and Up Study: a validation study.
AB - BACKGROUND: Increasingly, automated methods are being used to code free-text
medication data, but evidence on the validity of these methods is limited. AIM:
To examine the accuracy of automated coding of previously keyed in free-text
medication data compared with manual coding of original handwritten free-text
responses (the 'gold standard'). METHODS: A random sample of 500 participants
(475 with and 25 without medication data in the free-text box) enrolled in the 45
and Up Study was selected. Manual coding involved medication experts keying in
free-text responses and coding using Anatomical Therapeutic Chemical (ATC) codes
(i.e. chemical substance 7-digit level; chemical subgroup 5-digit;
pharmacological subgroup 4-digit; therapeutic subgroup 3-digit). Using keyed-in
free-text responses entered by non-experts, the automated approach coded entries
using the Australian Medicines Terminology database and assigned corresponding
ATC codes. RESULTS: Based on manual coding, 1377 free-text entries were recorded
and, of these, 1282 medications were coded to ATCs manually. The sensitivity of
automated coding compared with manual coding was 79% (n = 1014) for entries coded
at the exact ATC level, and 81.6% (n = 1046), 83.0% (n = 1064) and 83.8% (n =
1074) at the 5, 4 and 3-digit ATC levels, respectively. The sensitivity of
automated coding for blank responses was 100% compared with manual coding.
Sensitivity of automated coding was highest for prescription medications and
lowest for vitamins and supplements, compared with the manual approach. Positive
predictive values for automated coding were above 95% for 34 of the 38 individual
prescription medications examined. CONCLUSIONS: Automated coding for free-text
prescription medication data shows very high to excellent sensitivity and
positive predictive values, indicating that automated methods can potentially be
useful for large-scale, medication-related research.
PMID- 25848737
TI - Reliability study of clinical electronic records with paper records in the NSW
Public Oral Health Service.
AB - AIM: Electronic health record (EHR) data have great potential for reuse in
research and patient care quality improvement initiatives. However, in dual
systems, where both electronic and paper health records are used, inconsistencies
and errors may occur. The objective of this study was to determine the degree of
agreement between EHR clinical data and paper records for reuse in clinical oral
health research and quality improvement initiatives. METHODS: A random sample of
200 EHRs for adolescents from eight Area Health Services was obtained from the
Information System for Oral Health New South Wales database of 29 599 records,
and compared with 200 paper records for adolescents that were stored at clinics.
The records were analysed for data reliability. The electronic records were
percentage weighted to reflect the number of adolescents treated in each of the
Area Health Services. RESULTS: The results showed an overall 95.0% agreement
between the 200 individual EHRs and the 200 clinic-stored paper records. In 1.5%
of cases, information contained in the paper record was not uploaded into the
EHR, and in 3.5% of cases, information contained in the EHR was missing from the
paper record. CONCLUSIONS: It is possible to conclude that more deficiencies
occurred in paper records compared with EHRs. These deficiencies should be taken
into account if EHRs are to be reused for clinical oral health research or
quality improvement initiatives. Considering the missing data and the great
strides in information system technology, it would be logical to adopt one
system, with a focus on electronic records to replace the paper records.
PMID- 25848738
TI - Hepatitis C enhanced surveillance: results from a southeastern Sydney pilot
program.
AB - AIM: Hepatitis C virus (HCV) is a potentially serious bloodborne virus, which
persists in the majority of those infected. Long-term sequelae include liver
cirrhosis, liver cancer and premature death. Early identification of newly
acquired infection is important for protection of public health. Routine
surveillance based on laboratory notification of HCV infection is not sufficient
to differentiate between newly acquired and chronic infections. Enhanced
surveillance systems have been trialled globally in a number of settings. This
pilot program aimed to increase identification of newly acquired HCV cases in
southeastern Sydney residents and to ascertain the likely mode of transmission.
METHODS: All HCV notifications in southeastern Sydney residents with specimen
dates from 1 July to 31 December 2012 were included in a pilot program.
Demographic data, Australian Indigenous identification and previous laboratory
results were collected from electronic medical records, where available. Enhanced
surveillance forms were sent to referring doctors to seek information about
clinical symptoms and previous hepatitis C pathology. Data were collated to
assess, according to Australian national case definitions, whether cases were
newly acquired or not, or were unable to be determined on the available
information. RESULTS: There were 104 notifications of HCV infection during the
surveillance period. Forms were sent to 100 requesting doctors, with 72 forms
returned. Six newly acquired cases were identified, a rate of 8%, compared with 1
3% classified by routine surveillance. Twenty cases (28%) were not newly acquired
and the status of 46 (64%) was unable to be determined. Of the six newly acquired
cases, sexual transmission was deemed to be the likely route of exposure for four
cases, and injecting drug use for the remaining two. CONCLUSIONS: Enhanced
surveillance increased the rate of identification of newly acquired infections.
However, the process was labour-intensive and the status of most cases was unable
to be determined. Since identification of newly acquired cases has an important
public health benefit in understanding factors in disease transmission, other
approaches should be examined.
PMID- 25848739
TI - Piloting proactive marketing to recruit disadvantaged adults to a community-wide
obesity prevention program.
AB - Population-wide obesity prevention and treatment programs are fundamental to
addressing the increasing overweight and obesity rates in socioeconomically
disadvantaged populations. Innovative recruitment strategies, including proactive
marketing strategies, are needed to ensure such programs have universal reach and
target vulnerable populations. This study aimed to determine the success of
proactive recruitment to Australia's Get Healthy Information and Coaching
Service(r) (GHS) and to assess whether the recruitment strategy influenced
participants' outcomes. Sociodemographic information was collected from all GHS
participants who joined the service between February 2009 and August 2013, and
anthropometric information regarding behavioural risk factors was collected from
all GHS coaching participants at baseline and six months. Data were analysed
according to the participants' referral source (self-referral and secondary
referral versus proactive recruitment). Participants recruited through proactive
marketing were more likely to be male, aged 50 years or older, have high school
education, not be in paid employment and be from the lowest three quintiles of
socioeconomic advantage. The risk factor profile of coaching participants
recruited through proactive marketing did not vary significantly from those
recruited via other mechanisms, although they were less likely to be obese and
less likely to have a higher 'at risk' waist circumference measurement.
Proactively recruited coaching participants reported significant improvements
from baseline to six months (consistent with improvements made by participants
recruited through other strategies), although they were significantly more likely
to withdraw from coaching before they completed the six-month program.Proactive
marketing facilitated use of an obesity prevention service; similar services may
have greater reach if proactive marketing recruitment strategies are used. These
strategies could be encouraged to assist such services to achieve optimal
population impact among hard-to-reach populations.
PMID- 25848740
TI - Health promotion 'on steroids': the value of an experiential approach to promote
rapid HIV testing in NSW, Australia.
AB - In 2012, there was a sharp increase in human immunodeficiency virus (HIV)
notifications in New South Wales (NSW), Australia, following a 10-year period of
relative stability. This increase, among other factors, triggered the development
of a new HIV strategy that included renewed efforts to increase testing to
improve early diagnosis, enable early treatment and reduce the risk of onward
transmission. This article describes the activities conducted by NSW Health and
partner organisations during November 2013 in the week before World AIDS Day
(phase one (P1)) and HIV testing week in July 2014 (phase 2 (P2)). A model of pop
up HIV testing, new to Australia, was used to take testing to those most at risk
of infection, and was promoted through social media and experiential techniques.
During P1, an average of seven tests per hour were conducted at the pop-up
service, compared with four tests per hour at a fast-track screening service in a
nearby sexual health clinic. During HIV testing week, the campaign hashtag was
mentioned an average of 56 times per day, following a baseline of six mentions
per day one week before. The estimated total social media reach was 549,769
people via 459 posts. The pop-up testing model proved popular, and the use of
social media and experiential techniques has extended the reach of the 'test
more' messages. Further research is required to determine causality between
specific HIV messaging and experiential techniques and testing rates.
PMID- 25848741
TI - Plain packaging an "extraordinary success".
PMID- 25848742
TI - NSW pledges support for FASD.
PMID- 25848743
TI - 'No jab, no pay' recommendation raises concerns.
PMID- 25848744
TI - The asymmetry of female meiosis reduces the frequency of inheritance of unpaired
chromosomes.
AB - Trisomy, the presence of a third copy of one chromosome, is deleterious and
results in inviable or defective progeny if passed through the germ line. Random
segregation of an extra chromosome is predicted to result in a high frequency of
trisomic offspring from a trisomic parent. Caenorhabditis elegans with trisomy of
the X chromosome, however, have far fewer trisomic offspring than expected. We
found that the extra X chromosome was preferentially eliminated during anaphase I
of female meiosis. We utilized a mutant with a specific defect in pairing of the
X chromosome as a model to investigate the apparent bias against univalent
inheritance. First, univalents lagged during anaphase I and their movement was
biased toward the cortex and future polar body. Second, late-lagging univalents
were frequently captured by the ingressing polar body contractile ring. The
asymmetry of female meiosis can thus partially correct pre-existing trisomy.
PMID- 25848745
TI - In vivo targeting of de novo DNA methylation by histone modifications in yeast
and mouse.
AB - Methylation of cytosines (5(me)C) is a widespread heritable DNA modification.
During mammalian development, two global demethylation events are followed by
waves of de novo DNA methylation. In vivo mechanisms of DNA methylation
establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae
as a system lacking DNA methylation to define the chromatin features influencing
the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4
methylation are mutually exclusive and that DNMT3B is co-localized with H3K36
methylated regions. In support of this observation, DNA methylation analysis in
yeast strains without Set1 and Set2 shows an increase of relative 5(me)C levels
at the transcription start site and a decrease in the gene-body, respectively. We
extend our observation to the murine male germline, where H3K4me3 is strongly
anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These
results show the importance of H3K36 methylation for gene-body DNA methylation in
vivo.
PMID- 25848746
TI - ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte
dedifferentiation and proliferation.
AB - The murine neonatal heart can regenerate after injury through cardiomyocyte (CM)
proliferation, although this capacity markedly diminishes after the first week of
life. Neuregulin-1 (NRG1) administration has been proposed as a strategy to
promote cardiac regeneration. Here, using loss- and gain-of-function genetic
tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration.
NRG1-induced CM proliferation diminished one week after birth owing to a
reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is
required for CM proliferation at embryonic/neonatal stages. Induction of a
constitutively active ERBB2 (caERBB2) in neonatal, juvenile and adult CMs
resulted in cardiomegaly, characterized by extensive CM hypertrophy,
dedifferentiation and proliferation, differentially mediated by ERK, AKT and
GSK3beta/beta-catenin signalling pathways. Transient induction of caERBB2
following myocardial infarction triggered CM dedifferentiation and proliferation
followed by redifferentiation and regeneration. Thus, ERBB2 is both necessary for
CM proliferation and sufficient to reactivate postnatal CM proliferative and
regenerative potentials.
PMID- 25848747
TI - Independent and coordinate trafficking of single Drosophila germ plasm mRNAs.
AB - Messenger RNA localization is a conserved mechanism for spatial control of
protein synthesis, with key roles in generating cellular and developmental
asymmetry. Whereas different transcripts may be targeted to the same subcellular
domain, the extent to which their localization is coordinated is unclear. Using
quantitative single-molecule imaging, we analysed the assembly of Drosophila germ
plasm mRNA granules inherited by nascent germ cells. We find that the germ-cell
destined transcripts nanos, cyclin B and polar granule component travel within
the oocyte as ribonucleoprotein particles containing single mRNA molecules but co
assemble into multi-copy heterogeneous granules selectively at the posterior of
the oocyte. The stoichiometry and dynamics of assembly indicate a defined
stepwise sequence. Our data suggest that co-packaging of these transcripts
ensures their effective segregation to germ cells. In contrast,
compartmentalization of the germline determinant oskar mRNA into different
granules limits its entry into germ cells. This exclusion is required for proper
germline development.
PMID- 25848748
TI - Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary
fibrosis and telomere shortening.
AB - Idiopathic pulmonary fibrosis (IPF) is an age-related disease featuring
progressive lung scarring. To elucidate the molecular basis of IPF, we performed
exome sequencing of familial kindreds with pulmonary fibrosis. Gene burden
analysis comparing 78 European cases and 2,816 controls implicated PARN, an
exoribonuclease with no previous connection to telomere biology or disease, with
five new heterozygous damaging mutations in unrelated cases and none in controls
(P = 1.3 * 10(-8)); mutations were shared by all affected relatives (odds in
favor of linkage = 4,096:1). RTEL1, an established locus for dyskeratosis
congenita, harbored significantly more new damaging and missense variants at
conserved residues in cases than in controls (P = 1.6 * 10(-6)). PARN and RTEL1
mutation carriers had shortened leukocyte telomere lengths, and we observed
epigenetic inheritance of short telomeres in family members. Together, these
genes explain ~7% of familial pulmonary fibrosis and strengthen the link between
lung fibrosis and telomere dysfunction.
PMID- 25848749
TI - Exploring population size changes using SNP frequency spectra.
AB - Inferring demographic history is an important task in population genetics. Many
existing inference methods are based on predefined simplified population models,
which are more suitable for hypothesis testing than exploratory analysis. We
developed a novel model-flexible method called stairway plot, which infers
changes in population size over time using SNP frequency spectra. This method is
applicable for whole-genome sequences of hundreds of individuals. Using extensive
simulation, we demonstrate the usefulness of the method for inferring demographic
history, especially recent changes in population size. We apply the method to the
whole-genome sequence data of 9 populations from the 1000 Genomes Project and
show a pattern of fluctuations in human populations from 10,000 to 200,000 years
ago.
PMID- 25848751
TI - Mutational landscape and clonal architecture in grade II and III gliomas.
AB - Grade II and III gliomas are generally slowly progressing brain cancers, many of
which eventually transform into more aggressive tumors. Despite recent findings
of frequent mutations in IDH1 and other genes, knowledge about their pathogenesis
is still incomplete. Here, combining two large sets of high-throughput sequencing
data, we delineate the entire picture of genetic alterations and affected
pathways in these glioma types, with sensitive detection of driver genes. Grade
II and III gliomas comprise three distinct subtypes characterized by discrete
sets of mutations and distinct clinical behaviors. Mutations showed significant
positive and negative correlations and a chronological hierarchy, as inferred
from different allelic burdens among coexisting mutations, suggesting that there
is functional interplay between the mutations that drive clonal selection.
Extensive serial and multi-regional sampling analyses further supported this
finding and also identified a high degree of temporal and spatial heterogeneity
generated during tumor expansion and relapse, which is likely shaped by the
complex but ordered processes of multiple clonal selection and evolutionary
events.
PMID- 25848750
TI - Transposon mutagenesis identifies genetic drivers of Braf(V600E) melanoma.
AB - Although nearly half of human melanomas harbor oncogenic BRAF(V600E) mutations,
the genetic events that cooperate with these mutations to drive melanogenesis are
still largely unknown. Here we show that Sleeping Beauty (SB) transposon-mediated
mutagenesis drives melanoma progression in Braf(V600E) mutant mice and identify
1,232 recurrently mutated candidate cancer genes (CCGs) from 70 SB-driven
melanomas. CCGs are enriched in Wnt, PI3K, MAPK and netrin signaling pathway
components and are more highly connected to one another than predicted by chance,
indicating that SB targets cooperative genetic networks in melanoma. Human
orthologs of >500 CCGs are enriched for mutations in human melanoma or showed
statistically significant clinical associations between RNA abundance and
survival of patients with metastatic melanoma. We also functionally validate
CEP350 as a new tumor-suppressor gene in human melanoma. SB mutagenesis has thus
helped to catalog the cooperative molecular mechanisms driving BRAF(V600E)
melanoma and discover new genes with potential clinical importance in human
melanoma.
PMID- 25848752
TI - Genetic conflict reflected in tissue-specific maps of genomic imprinting in human
and mouse.
AB - Genomic imprinting is an epigenetic process that restricts gene expression to
either the maternally or paternally inherited allele. Many theories have been
proposed to explain its evolutionary origin, but understanding has been limited
by a paucity of data mapping the breadth and dynamics of imprinting within any
organism. We generated an atlas of imprinting spanning 33 mouse and 45 human
developmental stages and tissues. Nearly all imprinted genes were imprinted in
early development and either retained their parent-of-origin expression in adults
or lost it completely. Consistent with an evolutionary signature of parental
conflict, imprinted genes were enriched for coexpressed pairs of maternally and
paternally expressed genes, showed accelerated expression divergence between
human and mouse, and were more highly expressed than their non-imprinted
orthologs in other species. Our approach demonstrates a general framework for the
discovery of imprinting in any species and sheds light on the causes and
consequences of genomic imprinting in mammals.
PMID- 25848753
TI - Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and
lysosome-autophagosome dysfunction.
AB - Pediatric-onset ataxias often present clinically as developmental delay and
intellectual disability, with prominent cerebellar atrophy as a key
neuroradiographic finding. Here we describe a new clinically distinguishable
recessive syndrome in 12 families with cerebellar atrophy together with ataxia,
coarsened facial features and intellectual disability, due to truncating
mutations in the sorting nexin gene SNX14, encoding a ubiquitously expressed
modular PX domain-containing sorting factor. We found SNX14 localized to
lysosomes and associated with phosphatidylinositol (3,5)-bisphosphate, a key
component of late endosomes/lysosomes. Patient-derived cells showed engorged
lysosomes and a slower autophagosome clearance rate upon autophagy induction by
starvation. Zebrafish morphants for snx14 showed dramatic loss of cerebellar
parenchyma, accumulation of autophagosomes and activation of apoptosis. Our
results characterize a unique ataxia syndrome due to biallelic SNX14 mutations
leading to lysosome-autophagosome dysfunction.
PMID- 25848754
TI - FBXL10 protects Polycomb-bound genes from hypermethylation.
AB - Nearly all CpG-dense promoters are occupied by the multidomain chromosomal
protein FBXL10. We show here that complete inactivation of the Fbxl10 gene leads
to dense de novo methylation only of promoters that are co-occupied by both
FBXL10 and Polycomb repressive complexes; this methylation results in pervasive
defects in embryonic development and the death of homozygous Fbxl10-mutant
embryos at midgestation. Deletion of key components of Polycomb repressive
complexes 1 and 2 did not lead to ectopic genomic methylation. These results
indicate that FBXL10 protects Polycomb-occupied promoters against ectopic de novo
methylation. To our knowledge, FBXL10 is the first reported factor whose loss
leads to a gain in genomic DNA methylation.
PMID- 25848756
TI - Regulatory T cells: Young AIREs go on to rule.
PMID- 25848757
TI - Coverage-dependent thermodynamic analysis of the formation of water and hydrogen
peroxide on a platinum model catalyst.
AB - Understanding the selectivity of the oxygen reduction reaction, especially the
formation of water versus hydrogen peroxide in fuel cells, is an ongoing
challenge in electrochemistry, surface science and catalysis. In this study, we
propose a comprehensive thermodynamic analysis of the reaction intermediates for
the formation of water on Pt(111). Density functional theory calculations of all
the elementary steps linking hydroxyl and hydroperoxyl surface species with water
and hydrogen peroxide have been performed at low (1/12 ML, ML = monolayer) and
high (1/4 ML) coverages. The reaction energy variation for the two competing
elementary events (molecular oxygen dissociation and hydroperoxyl formation) is
strongly coverage-dependent. For the direct dissociation, an increase is observed
at low coverage with respect to the usual high coverage picture. The stability of
the reaction intermediates is investigated from thermodynamic diagrams. At 353 K
and a total pressure of 1 atm, water and hydroxyl surface species are expected to
compete for adsorption on Pt(111).
PMID- 25848755
TI - The development and in vivo function of T helper 9 cells.
AB - The specialized cytokine secretion profiles of T helper (TH) cells are the basis
for a focused and efficient immune response. On the twentieth anniversary of the
first descriptions of the cytokine signals that promote the differentiation of
interleukin-9 (IL-9)-secreting T cells, this Review focuses on the extracellular
signals and the transcription factors that promote the development of what we now
term TH9 cells, which are characterized by the production of this cytokine. We
summarize our current understanding of the contribution of TH9 cells to both
effective immunity and immunopathological disease, and we propose that TH9 cells
could be targeted for the treatment of allergic and autoimmune disease.
PMID- 25848758
TI - Aberrant beliefs and reasoning.
PMID- 25848759
TI - Effects of Tithonia diversifolia (Hemsl.) A. Gray extract on adipocyte
differentiation of human mesenchymal stem cells.
AB - Tithonia diversifolia (Hemsl.) A. Gray (Asteraceae) is widely used in traditional
medicine. There is increasing interest on the in vivo protective effects of
natural compounds contained in plants against oxidative damage caused from
reactive oxygen species. In the present study the total phenolic and flavonoid
contents of aqueous, methanol and dichloromethane extracts of leaves of Tithonia
diversifolia (Hemsl.) A. Gray were determined; furthermore, free radical
scavenging capacity of each extract and the ability of these extracts to inhibit
in vitro plasma lipid peroxidation were also evaluated. Since oxidative stress
may be involved in trasformation of pre-adipocytes into adipocytes, to test the
hypothesis that Tithonia extract may also affect adipocyte differentiation, human
mesenchymal stem cell cultures were treated with Tithonia diversifolia aqueous
extract and cell viability, free radical levels, Oil-Red O staining and western
bolt analysis for heme oxygenase and 5'-adenosine monophoshate-activated protein
kinase were carried out. Results obtained in the present study provide evidence
that Tithonia diversifolia (Hemsl.) A. Gray exhibits interesting health promoting
properties, resulting both from its free radical scavenger capacity and also by
induction of protective cellular systems involved in cellular stress defenses and
in adipogenesis of mesenchymal cells.
PMID- 25848760
TI - A common variant of ubiquinol-cytochrome c reductase complex is associated with
DDH.
AB - PURPOSE: Genetic basis of Developmental dysplasia of the hip (DDH) remains
largely unknown. To find new susceptibility genes for DDH, we carried out a
genome-wide association study (GWAS) for DDH. METHODS: We enrolled 386 radiology
confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide
association study (GWAS). Quality-control was conducted at both the sample and
single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case
control study to replicate the association between a promising loci, rs6060373 in
UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B).
RESULTS: In the DDH GWAS discovering stage, 51 SNPs showed significance of less
than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC,
all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373
in set A showed the minor allele A as a promising risk allele (p = 4.82*10-7). In
set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B
produced another significant result (p = 0.0338) with an odds ratio of 1.18 for
risk allele A. Combining set A and set B, we identified a total p value of
3.63*10-6 with the odds ratio of 1.35 (1.19-1.53) for allele A. CONCLUSION: Our
study demonstrates common variants of UQCC, specifically rs6060373, are
associated with DDH in Han Chinese population.
PMID- 25848761
TI - Postnatal depression among rural women in South India: do socio-demographic,
obstetric and pregnancy outcome have a role to play?
AB - INTRODUCTION: Postnatal depression (PND) is one of the most common
psychopathology and is considered as a serious public health issue because of its
devastating effects on mother, family, and infant or the child. OBJECTIVE: To
elicit socio-demographic, obstetric and pregnancy outcome predictors of Postnatal
Depression (PND) among rural postnatal women in Karnataka state, India. DESIGN:
Hospital based analytical cross sectional study. SETTING: A rural tertiary care
hospital of Mandya District, Karnataka state, India. SAMPLE: PND prevalence based
estimated sample of 102 women who came for postnatal follow up from 4th to 10th
week of lactation. METHOD: Study participants were interviewed using validated
kannada version of Edinburgh Postnatal Depression Scale (EPDS). Cut-off score of
>= 13 was used as high risk of PND. The percentage of women at risk of PND was
estimated, and differences according to socio-demographic, obstetric and
pregnancy outcome were described. Logistic regression was applied to identify the
independent predictors of PND risk. MAIN OUTCOME MEASURES: Prevalence, Odds ratio
(OR) and adjusted (adj) OR of PND. RESULTS: Prevalence of PND was 31.4% (95% CI
22.7-41.4%). PND showed significant (P < 0.05) association with joint family,
working women, non-farmer husbands, poverty, female baby and pregnancy
complications or known medical illness. In binomial logistic regression poverty
(adjOR: 11.95, 95% CI:1.36-105), birth of female baby (adjOR: 3.6, 95% CI:1.26
10.23) and pregnancy complications or known medical illness (adjOR: 17.4, 95%
CI:2.5-121.2) remained as independent predictors of PND. CONCLUSION: Risk of PND
among rural postnatal women was high (31.4%). Birth of female baby, poverty and
complications in pregnancy or known medical illness could predict the high risk
of PND. PND screening should be an integral part of postnatal care. Capacity
building of grass root level workers and feasibility trials for screening PND by
them are needed.
PMID- 25848763
TI - Multi-lineage differentiation of human umbilical cord Wharton's Jelly Mesenchymal
Stromal Cells mediates changes in the expression profile of stemness markers.
AB - Wharton's Jelly- derived Mesenchymal stem cells (WJ-MSCs) have gained interest as
an alternative source of stem cells for regenerative medicine because of their
potential for self-renewal, differentiation and unique immunomodulatory
properties. Although many studies have characterized various WJ-MSCs
biologically, the expression profiles of the commonly used stemness markers have
not yet been addressed. In this study, WJ-MSCs were isolated and characterized
for stemness and surface markers expression. Flow cytometry, immunofluorescence
and qRT-PCR analysis revealed predominant expression of CD29, CD44, CD73, CD90,
CD105 and CD166 in WJ-MSCs, while the hematopoietic and endothelial markers were
absent. Differential expression of CD 29, CD90, CD105 and CD166 following
adipogenic, osteogenic and chondrogenic induction was observed. Furthermore, our
results demonstrated a reduction in CD44 and CD73 expressions in response to the
tri-lineage differentiation induction, suggesting that they can be used as
reliable stemness markers, since their expression was associated with
undifferentiated WJ-MSCs only.
PMID- 25848762
TI - The determinants of traditional medicine use in Northern Tanzania: a mixed
methods study.
AB - INTRODUCTION: Traditional medicines are an important part of healthcare in sub
Saharan Africa, and building successful disease treatment programs that are
sensitive to traditional medicine practices will require an understanding of
their current use and roles, including from a biomedical perspective. Therefore,
we conducted a mixed-method study in Northern Tanzania in order to characterize
the extent of and reasons for the use of traditional medicines among the general
population so that we can better inform public health efforts in the region.
METHODS: Between December 2013 and June 2014 in Kilimanjaro, Tanzania, we
conducted 5 focus group discussions and 27 in-depth interviews of key informants.
The data from these sessions were analyzed using an inductive framework method
with cultural insider-outsider coding. From these results, we developed a
structured survey designed to test different aspects of traditional medicine use
and administered it to a random sample of 655 adults from the community. The
results were triangulated to explore converging and diverging themes. RESULTS:
Most structured survey participants (68%) reported knowing someone who frequently
used traditional medicines, and the majority (56%) reported using them themselves
in the previous year. The most common uses were for symptomatic ailments (42%),
chronic diseases (15%), reproductive problems (11%), and malaria/febrile
illnesses (11%). We identified five major determinants for traditional medicine
use in Northern Tanzania: biomedical healthcare delivery, credibility of
traditional practices, strong cultural identities, individual health status, and
disease understanding. CONCLUSIONS: In order to better formulate effective local
disease management programs that are sensitive to TM practices, we described the
determinants of TM use. Additionally, we found TM use to be high in Northern
Tanzania and that its use is not limited to lower-income areas or rural settings.
After symptomatic ailments, chronic diseases were reported as the most common
reason for TM use which may be particularly important in Northern Tanzania where
non-communicable diseases are a rapidly growing burden.
PMID- 25848764
TI - Myocardial feature tracking reduces observer-dependence in low-dose dobutamine
stress cardiovascular magnetic resonance.
AB - OBJECTIVES: To determine whether quantitative wall motion assessment by CMR
myocardial feature tracking (CMR-FT) would reduce the impact of observer
experience as compared to visual analysis in patients with ischemic
cardiomyopathy (ICM). METHODS: 15 consecutive patients with ICM referred for
assessment of hibernating myocardium were studied at 3 Tesla using SSFP cine
images at rest and during low dose dobutamine stress (5 and 10 MUg/kg/min of
dobutamine). Conventional visual, qualitative analysis was performed
independently and blinded by an experienced and an inexperienced reader, followed
by post-processing of the same images by CMR-FT to quantify subendocardial and
subepicardial circumferential (Eccendo and Eccepi) and radial (Err) strain.
Receiver operator characteristics (ROC) were assessed for each strain parameter
and operator to detect the presence of inotropic reserve as visually defined by
the experienced observer. RESULTS: 141 segments with wall motion abnormalities at
rest were eligible for the analysis. Visual scoring of wall motion at rest and
during dobutamine was significantly different between the experienced and the
inexperienced observer (p<0.001). All strain values (Eccendo, Eccepi and Err)
derived during dobutamine stress (5 and 10 MUg/kg/min) showed similar diagnostic
accuracy for the detection of contractile reserve for both operators with no
differences in ROC (p>0.05). Eccendo was the most accurate (AUC of 0.76, 10
MUg/kg/min of dobutamine) parameter. Diagnostic accuracy was worse for resting
strain with differences between operators for Eccendo and Eccepi (p<0.05) but not
Err (p>0.05). CONCLUSION: Whilst visual analysis remains highly dependent on
operator experience, quantitative CMR-FT analysis of myocardial wall mechanics
during DS-CMR provides diagnostic accuracy for the detection of inotropic reserve
regardless of operator experience and hence may improve diagnostic robustness of
low-dose DS-CMR in clinical practice.
PMID- 25848765
TI - High expression of KCa3.1 in patients with clear cell renal carcinoma predicts
high metastatic risk and poor survival.
AB - BACKGROUND: Ca2+-activated K+ channels have been implicated in cancer cell
growth, metastasis, and tumor angiogenesis. Here we hypothesized that high mRNA
and protein expression of the intermediate-conductance Ca2+-activated K+ channel,
KCa3.1, is a molecular marker of clear cell Renal Cell Carcinoma (ccRCC) and
metastatic potential and survival. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed
channel expression by qRT-PCR, immunohistochemistry, and patch-clamp in ccRCC and
benign oncocytoma specimens, in primary ccRCC and oncocytoma cell lines, as well
as in two ccRCC cell lines (Caki-1 and Caki-2). CcRCC specimens contained 12-fold
higher mRNA levels of KCa3.1 than oncocytoma specimens. The large-conductance
channel, KCa1.1, was 3-fold more highly expressed in ccRCC than in oncocytoma.
KCa3.1 mRNA expression in ccRCC was 2-fold higher than in the healthy cortex of
the same kidney. Disease specific survival trended towards reduction in the
subgroup of high-KCa3.1-expressing tumors (p<0.08 vs. low-KCa3.1-expressing
tumors). Progression-free survival (time to metastasis/recurrence) was reduced
significantly in the subgroup of high-KCa3.1-expressing tumors (p<0.02, vs. low
KCa3.1-expressing tumors). Immunohistochemistry revealed high protein expression
of KCa3.1 in tumor vessels of ccRCC and oncocytoma and in a subset of ccRCC
cells. Oncocytoma cells were devoid of KCa3.1 protein. In a primary ccRCC cell
line and Caki-1/2-ccRCC cells, we found KCa3.1-protein as well as TRAM-34
sensitive KCa3.1-currents in a subset of cells. Furthermore, Caki-1/2-ccRCC cells
displayed functional Paxilline-sensitive KCa1.1 currents. Neither KCa3.1 nor
KCa1.1 were found in a primary oncocytoma cell line. Yet KCa-blockers, like TRAM
34 (KCa3.1) and Paxilline (KCa1.1), had no appreciable effects on Caki-1
proliferation in-vitro. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated
expression of KCa3.1 in ccRCC but not in benign oncocytoma. Moreover, high KCa3.1
mRNA expression levels were indicative of low disease specific survival of ccRCC
patients, short progression-free survival, and a high metastatic potential.
Therefore, KCa3.1 is of prognostic value in ccRCC.
PMID- 25848766
TI - Genomic heterogeneity of osteosarcoma - shift from single candidates to
functional modules.
AB - Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic
level a highly variable degree of alterations in nearly all chromosomal regions
and between individual tumors is observable. This hampers the identification of
common drivers in OS biology. To identify the common molecular mechanisms
involved in the maintenance of OS, we follow the hypothesis that all the copy
number-associated differences between the patients are intercepted on the level
of the functional modules. The implementation is based on a network approach
utilizing copy number associated genes in OS, paired expression data and protein
interaction data. The resulting functional modules of tightly connected genes
were interpreted regarding their biological functions in OS and their potential
prognostic significance. We identified an osteosarcoma network assembling well
known and lesser-known candidates. The derived network shows a significant
connectivity and modularity suggesting that the genes affected by the
heterogeneous genetic alterations share the same biological context. The network
modules participate in several critical aspects of cancer biology like DNA damage
response, cell growth, and cell motility which is in line with the hypothesis of
specifically deregulated but functional modules in cancer. Further, we could
deduce genes with possible prognostic significance in OS for further
investigation (e.g. EZR, CDKN2A, MAP3K5). Several of those module genes were
located on chromosome 6q. The given systems biological approach provides evidence
that heterogeneity on the genomic and expression level is ordered by the
biological system on the level of the functional modules. Different genomic
aberrations are pointing to the same cellular network vicinity to form vital, but
already neoplastically altered, functional modules maintaining OS. This
observation, exemplarily now shown for OS, has been under discussion already for
a longer time, but often in a hypothetical manner, and can here be exemplified
for OS.
PMID- 25848767
TI - Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury
by modulating pro-inflammatory mediators.
AB - Immune-complexes play an important role in the inflammatory diseases of the lung.
Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung
injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including
GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in
the lungs and in the neutrophils. However, the role of pulmonary GABABR
activation in the context of neutrophil-mediated ALI has not been determined.
Thus, the objective of the current study was to determine whether administration
of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized
that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR
expression. Rats were subjected to sham injury or IC-induced ALI and two hours
later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2
additional hours and sacrificed. ALI was assessed by vascular leakage, histology,
TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis
factor alpha (TNF-alpha and interleukin-1 receptor associated protein (IL-1R
AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung
GABABR2 expression, increased phospho-p38 MAPK, promoted IkappaB degradation and
increased neutrophil influx in the lung. Administration of baclofen, after
initiation of ALI, restored GABABR expression, which was inhibited in the
presence of a GABABR antagonist, CGP52432. Baclofen administration activated
pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IkappaB
degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF
alpha and IL-1betaAcP release and promoted BAL neutrophil apoptosis. Protective
effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF
alpha- and IL-1beta-mediated inflammatory signaling. Interestingly, GABABR2
expression was regulated in the type II pneumocytes in lung tissue sections from
lung injured patients, further suggesting a physiological role for GABABR2 in the
repair process of lung damage. GABABR2 agonists may play a potential therapeutic
role in ALI.
PMID- 25848769
TI - Home sampling for sexually transmitted infections and HIV in men who have sex
with men: a prospective observational study.
AB - To determine uptake of home sampling kit (HSK) for STI/HIV compared to clinic
based testing, whether the availability of HSK would increase STI testing rates
amongst HIV infected MSM, and those attending a community-based HIV testing
clinic compared to historical control. Prospective observational study in three
facilities providing STI/HIV testing services in Brighton, UK was conducted.
Adult MSM attending/contacting a GUM clinic requesting an STI screen (group 1),
HIV infected MSM attending routine outpatient clinic (group 2), and MSM attending
a community-based rapid HIV testing service (group 3) were eligible. Participants
were required to have no symptomatology consistent with STI and known to be
immune to hepatitis A and B (group 1). Eligible men were offered a HSK to obtain
self-collected specimens as an alternative to routine testing. HSK uptake
compared to conventional clinic-based STI/HIV testing in group 1, increase in STI
testing rates due to availability of HSK compared to historical controls in group
2 and 3, and HSK return rates in all settings were calculated. Among the 128
eligible men in group 1, HSK acceptance was higher (62.5% (95% CI: 53.5-70.9))
compared to GUM clinic-based testing (37.5% (95% CI: 29.1-46.5)), (p = 0.0004).
Two thirds of eligible MSM offered an HSK in all three groups accepted it, but
HSK return rates varied (highest in group 1, 77.5%, lowest in group 3, 16%). HSK
for HIV testing was acceptable to 81% of men in group 1. Compared to historical
controls, availability of HSK increased the proportion of MSM testing for STIs in
group 2 but not in group 3. HSK for STI/HIV offers an alternative to conventional
clinic-based testing for MSM seeking STI screening. It significantly increases
STI testing uptake in HIV infected MSM. HSK could be considered as an adjunct to
clinic-based services to further improve STI/HIV testing in MSM.
PMID- 25848768
TI - Ketones prevent oxidative impairment of hippocampal synaptic integrity through
KATP channels.
AB - Dietary and metabolic therapies are increasingly being considered for a variety
of neurological disorders, based in part on growing evidence for the
neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we
demonstrated that ketones afford hippocampal synaptic protection against
exogenous oxidative stress, but the mechanisms underlying these actions remain
unclear. Recent studies have shown that ketones may modulate neuronal firing
through interactions with ATP-sensitive potassium (KATP) channels. Here, we used
a combination of electrophysiological, pharmacological, and biochemical assays to
determine whether hippocampal synaptic protection by ketones is a consequence of
KATP channel activation. Ketones dose-dependently reversed oxidative impairment
of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity,
and this action was mirrored by the KATP channel activator diazoxide. Inhibition
of KATP channels reversed ketone-evoked hippocampal protection, and genetic
ablation of the inwardly rectifying K+ channel subunit Kir6.2, a critical
component of KATP channels, partially negated the synaptic protection afforded by
ketones. This partial protection was completely reversed by co-application of the
KATP blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of
oxidative injury, ketones induce synaptic protection in part through activation
of KATP channels.
PMID- 25848770
TI - Membrane bound GSK-3 activates Wnt signaling through disheveled and arrow.
AB - Wnt ligands and their downstream pathway components coordinate many developmental
and cellular processes. In adults, they regulate tissue homeostasis through
regulation of stem cells. Mechanistically, signal transduction through this
pathway is complicated by pathway components having both positive and negative
roles in signal propagation. Here we examine the positive role of GSK-3/Zw3 in
promoting signal transduction at the plasma membrane. We find that targeting GSK
3 to the plasma membrane activates signaling in Drosophila embryos. This
activation requires the presence of the co-receptor Arrow-LRP5/6 and the pathway
activating protein Disheveled. Our results provide genetic evidence for
evolutionarily conserved, separable roles for GSK-3 at the membrane and in the
cytosol, and are consistent with a model where the complex cycles from cytosol to
membrane in order to promote signaling at the membrane and to prevent it in the
cytosol.
PMID- 25848771
TI - A multi-layered protein network stabilizes the Escherichia coli FtsZ-ring and
modulates constriction dynamics.
AB - The prokaryotic tubulin homolog, FtsZ, forms a ring-like structure (FtsZ-ring) at
midcell. The FtsZ-ring establishes the division plane and enables the assembly of
the macromolecular division machinery (divisome). Although many molecular
components of the divisome have been identified and their interactions
extensively characterized, the spatial organization of these proteins within the
divisome is unclear. Consequently, the physical mechanisms that drive divisome
assembly, maintenance, and constriction remain elusive. Here we applied single
molecule based superresolution imaging, combined with genetic and biophysical
investigations, to reveal the spatial organization of cellular structures formed
by four important divisome proteins in E. coli: FtsZ, ZapA, ZapB and MatP. We
show that these interacting proteins are arranged into a multi-layered protein
network extending from the cell membrane to the chromosome, each with unique
structural and dynamic properties. Further, we find that this protein network
stabilizes the FtsZ-ring, and unexpectedly, slows down cell constriction,
suggesting a new, unrecognized role for this network in bacterial cell division.
Our results provide new insight into the structure and function of the divisome,
and highlight the importance of coordinated cell constriction and chromosome
segregation.
PMID- 25848772
TI - How long can stool samples be fixed for an accurate diagnosis of soil-transmitted
helminth infection using Mini-FLOTAC?
AB - BACKGROUND: Kato-Katz is a widely used method for the diagnosis of soil
transmitted helminth infection. Fecal samples cannot be preserved, and hence,
should be processed on the day of collection and examined under a microscope
within 60 min of slide preparation. Mini-FLOTAC is a technique that allows
examining fixed fecal samples. We assessed the performance of Mini-FLOTAC using
formalin-fixed stool samples compared to Kato-Katz and determined the dynamics of
prevalence and intensity estimates of soil-transmitted helminth infection over a
31-day time period. METHODOLOGY: The study was carried out in late 2013 on Pemba
Island, Tanzania. Forty-one children were enrolled and stool samples were
subjected on the day of collection to a single Kato-Katz thick smear and Mini
FLOTAC examination; 12 aliquots of stool were fixed in 5% formalin and
subsequently examined by Mini-FLOTAC up to 31 days after collection. PRINCIPAL
FINDINGS: The combined results from Kato-Katz and Mini-FLOTAC revealed that 100%
of children were positive for Trichuris trichiura, 85% for Ascaris lumbricoides,
and 54% for hookworm. Kato-Katz and Mini-FLOTAC techniques found similar
prevalence estimates for A. lumbricoides (85% versus 76%), T. trichiura (98%
versus 100%), and hookworm (42% versus 51%). The mean eggs per gram of stool
(EPG) according to Kato-Katz and Mini-FLOTAC was 12,075 and 11,679 for A.
lumbricoides, 1,074 and 1,592 for T. trichiura, and 255 and 220 for hookworm,
respectively. The mean EPG from day 1 to 31 of fixation was stable for A.
lumbricoides and T. trichiura, but gradually declined for hookworm, starting at
day 15. CONCLUSIONS/SIGNIFICANCE: The findings of our study suggest that for a
qualitative diagnosis of soil-transmitted helminth infection, stool samples can
be fixed in 5% formalin for at least 30 days. However, for an accurate
quantitative diagnosis of hookworm, we suggest a limit of 15 days of
preservation. Our results have direct implication for integrating soil
transmitted helminthiasis into transmission assessment surveys for lymphatic
filariasis.
PMID- 25848774
TI - Correction: The alpha1,6-fucosyltransferase gene (fut8) from the Sf9 lepidopteran
insect cell line: insights into fut8 evolution.
PMID- 25848773
TI - Self-regulation of brain activity in patients with postherpetic neuralgia: a
double-blind randomized study using real-time FMRI neurofeedback.
AB - BACKGROUND: A pilot study has shown that real-time fMRI (rtfMRI) neurofeedback
could be an alternative approach for chronic pain treatment. Considering the
relative small sample of patients recruited and not strictly controlled
condition, it is desirable to perform a replication as well as a double-blinded
randomized study with a different control condition in chronic pain patients.
Here we conducted a rtfMRI neurofeedback study in a subgroup of pain patients -
patients with postherpetic neuralgia (PHN) and used a different sham
neurofeedback control. We explored the feasibility of self-regulation of the
rostral anterior cingulate cortex (rACC) activation in patients with PHN through
rtfMRI neurofeedback and regulation of pain perception. METHODS: Sixteen patients
(46-71 years) with PHN were randomly allocated to a experimental group (n = 8) or
a control group (n = 8). 2 patients in the control group were excluded for large
head motion. The experimental group was given true feedback information from
their rACC whereas the control group was given sham feedback information from
their posterior cingulate cortex (PCC). All subjects were instructed to perform
an imagery task to increase and decrease activation within the target region
using rtfMRI neurofeedback. RESULTS: Online analysis showed 6/8 patients in the
experimental group were able to increase and decrease the blood oxygen level
dependent (BOLD) fMRI signal magnitude during intermittent feedback training.
However, this modulation effect was not observed in the control group. Offline
analysis showed that the percentage of BOLD signal change of the target region
between the last and first training in the experimental group was significantly
different from the control group's and was also significantly different than 0.
The changes of pain perception reflected by numerical rating scale (NRS) in the
experimental group were significantly different from the control group. However,
there existed no significant correlations between BOLD signal change and NRS
change. CONCLUSION: Patients with PHN could learn to voluntarily control over
activation in rACC through rtfMRI neurofeedback and alter their pain perception
level. The present study may provide new evidence that rtfMRI neurofeedback
training may be a supplemental approach for chronic clinical pain management.
PMID- 25848775
TI - Association between perfluorinated compound exposure and miscarriage in Danish
pregnant women.
AB - Perfluorinated alkylated substances (PFAS) have been extensively used in consumer
products and humans are widely exposed to these persistent compounds. A recent
study found no association between exposure to perfluorooctanoic acid (PFOA) and
perfluorooctanesulfonic acid (PFOS) and miscarriage, but no studies have examined
adverse effect of the more recently introduced PFASs. We therefore conducted a
case-control study within a population-based, prospective cohort during 2010
2012. Newly pregnant women residing in the Municipality of Odense, Denmark were
invited to enroll in the Odense Child Cohort at their first antenatal visit
before pregnancy week 12. Among a total of 2,874 participating women, 88 suffered
a miscarriage and 59 had stored serum samples, of which 56 occurred before
gestational week 12. They were compared to a random sample (N=336) of delivering
women, who had also donated serum samples before week 12. Using a case-control
design, 51 of the women suffering a miscarriage were matched on parity and
gestational day of serum sampling with 204 delivering women. In a multiple
logistic regression with adjustment for age, BMI, parity and gestational age at
serum sampling, women with the highest tertile of exposure to perfluorononanoic
acid (PFNA) and perfluorodecanoic acid (PFDA) in pregnancy had odds ratios for
miscarriage of 16.5 (95% CI 7.4-36.6-36.5) and 2.67 (1.31-5.44), respectively, as
compared to the lowest tertile. In the matched data set, the OR were 37.9 (9.9
145.2) and 3.71 (1.60-8.60), respectively. The association with perfluorohexane
sulfonic acid (PFHxS) was in the same direction, but not statistically
significant, while no association was found with PFOA and PFOS. Our findings
require confirmation due to the possible public health importance, given that all
pregnant women are exposed to these widely used compounds.
PMID- 25848776
TI - Anatomically discrete sex differences in neuroplasticity in zebra finches as
reflected by perineuronal nets.
AB - Large morphological sex differences in the vertebrate brain were initially
identified in song control nuclei of oscines. Besides gross differences between
volumes of nuclei in males and females, sex differences also concern the size and
dendritic arborization of neurons and various neurochemical markers, such as the
calcium-binding protein parvalbumin (PV). Perineuronal nets (PNN) of the
extracellular matrix are aggregates of different compounds, mainly chondroitin
sulfate proteoglycans, that surround subsets of neurons, often expressing PV. PNN
develop in zebra finches song control nuclei around the end of the sensitive
period for song learning and tutor deprivation, known to delay the end of the
song learning sensitive period, decreases the numbers of PNN in HVC. We
demonstrate here the existence in zebra finches of a major sex difference (males
> females) affecting the number of PNN (especially those surrounding PV-positive
cells) in HVC and to a smaller extent the robust nucleus of the arcopallium, RA,
the two main nuclei controlling song production. These differences were not
present in Area X and LMAN, the lateral magnocellular nucleus of the anterior
nidopallium. A dense expression of material immunoreactive for chondroitin
sulfate was also detected in several nuclei of the auditory and visual pathways.
This material was often organized in perineuronal rings but quantification of
these PNN did not reveal any sex difference with the exception that the
percentage of PNN surrounding PV-ir cells in the dorsal lateral mesencephalic
nucleus, MLd, was larger in females than in males, a sex difference in the
opposite direction compared to what is seen in HVC and RA. These data confirm and
extend previous studies demonstrating the sex difference affecting PNN in HVC-RA
by showing that this sex difference is anatomically specific and does not concern
visual or auditory pathways.
PMID- 25848777
TI - Circumpapillary course of retinal pigment epithelium can be fit to sine wave and
amplitude of sine wave is significantly correlated with ovality ratio of optic
disc.
AB - The purpose of this study was to develop a method of quantifying the degree of
optic disc tilt in normal eyes. This was a prospective, observational cross
sectional study of 126 right eyes of 126 healthy volunteers. The optic disc tilt
was determined from the circular peripapillary optical coherence tomographic
(OCT) scan images. The course of the retinal pigment epithelium (RPE) layer in
the peripapillary cross sectional scan images was fit to a sine wave curve, and
the amplitude of the sine curve was used to reflect the degree of the optic disc
tilt in the optical axis. The repeatability of the amplitude determinations was
calculated. The correlation between the amplitude and the ovality ratio of the
optic disc was determined. The correlation between the amplitude and the body
height was also calculated. The mean amplitude was 36.6 +/- 17.5 pixels, which
was significantly and inversely correlated with the ovality ratio of the optic
disc (R = -0.59, P < 0.001). The intra-rater and inter-rater correlation
coefficients of the amplitude were significant high (P < 0.001, both). The
amplitude was significantly and inversely correlated with the body height (R =
0.38, P < 0.001), but not with the axial length. In conclusion, a sine wave
function can be used to describe the course of the RPE in the circumpapillary OCT
images. The results indicate that the amplitude of the sine wave can be used to
represent the degree of optic disc tilt. Thus, the sine wave analyses can be used
as a quantifiable and repeatable method to determine the optic disc tilt.
PMID- 25848778
TI - Diet and cancer risk/association between diet and risk of cancer.
AB - The article discusses problem of the association between diet and risk of cancer.
Author shows methodological concerns arising from the difficulty of selecting the
study groups, and also those dependent on ascertainment of the composition of the
diet for a long period of time necessary to establish the statistical
associations. Sources of carcinogenic substances in food include environmental
contaminants, chemicals synthesized in some plants and those which infiltrate the
food or are produced during the food processing. It is strongly advisable to
limit the content of carcinogenic substances in food by imposing Regulation (EC)
No 1881/2006 not only regarding products exported to the EU countries, but also
those intended for local market.
PMID- 25848779
TI - Food supplement-related risks in the light of internet and RASFF data.
AB - OBJECTIVE: Based on legal acts and RASFF information, this paper aimed at
evaluating available facts on food supplements in comparison to the most popular
data accessible via Internet for future and present consumers. MATERIAL AND
METHODS: Having analyzed legal acts and RASFF (Rapid Alert System for Food and
Feed) database, the authors attempted to verify what kind of information on food
supplements may be found by an Internet user, using the first webpage of
Google.pl. This search engine was used in this study as it gained the highest
popularity among Internet users. It was decided that exclusively search results
displayed on the first webpage would be subject to analysis as 91.5% of Internet
users limit their search to the first 9-10 results. Internet was searched using
the following two terms: 'supplement' and 'supplements' as well as terms
suggested by Google. pl. Subsequently, the results were subject to qualitative
and quantitative analyses. RESULTS: On the Internet, the most frequently searched
terms were: 'supplements' (243 000 000), 'supplement' (9 290 000), 'supplements
shop' (8 200 000). Having analyzed the content of particular websites,
information on certain products, given by their manufacturers may be found. Then,
data on supplement itself were provided, i.e. what is a supplement and when it
should be used. Expert articles (written by physicians, dieticians, pharmacists)
on a risk resulting from these products, including therapeutic indications or the
presence of unauthorized substances were identified considerably less frequently.
No warnings regarding the necessity of purchasing the products in legal and
verified places were found. CONCLUSIONS: There is a necessity of systemic
education of consumers on reasonable use of food supplements. It is also
advisable to consider the organization of alert system whose objective would be
to monitor adverse reactions caused by an intake of food supplements or novel
food launched into the country. To obtain reliable information on the composition
and effects of food supplements, potential consumer should contact physician or
dietician. Additionally, complementary information, using different sources with
an example being health-related portals, presenting articles written by
physicians or pharmacists, may be also searched.
PMID- 25848780
TI - An isolated outbreak of influenza A H1N1 in a haematological department during
post-pandemic period.
AB - INTRODUCTION AND OBJECTIVE: Influenza A H1N1 virus strain was associated with the
pandemic outbreak of febrile respiratory infections worldwide in 2009, however in
August 2010, the WHO announced that the world had entered the postpandemic
period. It offered specific recommendations for this period, including the
identification of clusters of severe respiratory disorders and deaths. Here we
report the fulminant course of influenza AH1N1 infection in the postpandemic
period in a group of patients in a single hematology department. We make an
attempt to identify potential risk factors and the mode of spreading, and to
provide recommendations for best practice. MATERIAL AND METHODS: We conducted a
retrospective analysis of a cluster of patients diagnosed with or suspected of
influenza A H1N1 infection in the period from December 2010 to March 2011.
RESULTS: Fourteen patients with hematological disorders unexpectedly developed
acute respiratory failure ARDS (Acute Respiratory Distress Syndrome). Of them,
nine tested positive for influenza A H1N1 in a screening test and eight in
confirmatory polymerase chain reaction. The infection was fatal in nine patients,
despite artificial ventilation in eight and oseltamivir administration in 11. Ten
were in reverse isolation according to CDC. No similar cases occurred in the
whole hospital concurrently, or in the hematology wards at any other time.
CONCLUSIONS: The occurrence of A H1N1 epidemics in a hematological ward in the
post-pandemic period highlights the importance of awareness of this complication,
prompt testing and antiviral treatment. Furthermore, it confirms the importance
of vaccinating patients and personnel against influenza as a prophylactic
measure.
PMID- 25848781
TI - Non-influenza viruses in acute respiratory infections among young children. High
prevalence of HMPV during the H1N1V.2009 pandemic in Poland.
AB - In Poland the majority of hospitalized cases of pneumonia (annually more than
70000) were reported without determination of an aetiological agent (J18 of ICD
10), also because diagnosis of viral ARTI is limited to identification of
influenza viruses or sometimes RSV. MATERIAL AND METHODS: For determination the
contribution of non-influenza viruses in ARTI among children, 381 nasopharyngeal
swabs from hospitalized in period X.2008-IV.2011y. children (aged 1 day - 5 y.o.)
were tested for RSV, HMPV, HEV/HRV, HPIV 1-3, HAdV, HBoV. RESULTS: At least one
viral agent was detected in 72.7% of patients. The most predominant was RSV
infection (49%), followed by HEV/HRV (15.5%); HMPV (8.7%), Adenoviruses (7.4%),
HPIVt.1-3 (5.8%) and HBoV (5.5%). Seven periods based on the median of examined
children/month were determined: 3 with increased number of ARTI. RSV infections,
diagnosed in all periods, were predominate in five periods, mainly in LRTI cases.
In the 3th period - HMPV was predominant, in the 5th - HEV/HRV. It was found that
clinical manifestation of HMPV infections varied depending on the period.
CONCLUSIONS: Relatively high prevalence of HBoV or HMPV cases of ARTI, especially
different clinical picture in some periods (ARTI without pneumonia or
bronchiolitis), indicated necessary of more detailed molecular and
epidemiological studies. Also our results indicate the need for improved
diagnostic capabilities of virological tests in acute upper and lower respiratory
tract infections in children.
PMID- 25848782
TI - Usefulness of laboratory methods in diagnosis of pertussis in adult with
paroxysmal cough.
AB - INTRODUCTION: Pertussis is an acute, highly contagious bacterial infection of
respiratory system caused by Bordetella pertussis. Principally, disease affects
young children, however, recently it is also reported in adolescents and adults.
Symptoms of pertussis in adults are non-specific, i.e. dry, paroxysmal and
protracted cough. Thus, it is rarely diagnosed in this group. AIM: This paper
aimed at evaluating the usefulness of the laboratory methods in diagnosis of
pertussis in adults based on a case presenting with dry, paroxysmal and chronic
cough. MATERIAL AND METHODS: Sputum (collected on 25th January 2013) and paired
serum samples (collected on 13th February and 19 April 2013) were tested.
Pertussis diagnostics involved culture, in-house PCR, real-time PCR and ELISA.
RESULTS: Sputum culture, using commercial medium Bordetella Selective Medium by
Oxoid did not reveal the presence of B. pertussis. Real-time PCR and PCR,
however, confirmed the presence of insertion sequence IS481 and pertussis toxin
promoter sequence ptx-Pr, markers indicative of B. pertussis infection.
Serological testing revealed the high titres of IgA, IgG and IgM antibodies to B.
pertussis in the first sample. In the second sample, collected 2 months following
the first one, a significant decrease in IgA antibodies was reported.
CONCLUSIONS: These data suggest a high usefulness of the laboratory methods in
the diagnosis of pertussis in adults with chronic cough. Application of such
methods ensures adequate diagnosis of disease, quick introduction of proper
treatment and implementation of procedures preventing the spread of infection.
PMID- 25848783
TI - Risk factors for tuberculosis and specific manifestations of disease.
AB - In countries with good epidemiological situation, incidence of tuberculosis (TB)
is relatively high in immigrants, prisoners, the homeless and unemployed. In a
number of regions, co-infection of Mycobacterium tuberculosis and HIV raises
difficulties in controlling TB epidemic. A problematic issue is also drug
resistance, especially in the countries of the former Union of Soviet Socialist
Republics (USSR). Neither co-infection of M.tuberculosis and HIV nor drug
resistance are of special concern in Poland. Incidence of extrapulmonary TB is
very diverse (6-44%), however, in Poland such manifestation of tuberculosis is
diagnosed rarely. There is a necessity of monitoring local epidemiological trends
and developing appropriate diagnostic and therapeutic models for better control
of infection.
PMID- 25848784
TI - Cerebrospinal fluid interleukin-6 concentration in patients with purulent,
bacterial meningitis - own observations.
AB - AIM: This study aimed at evaluating the usefulness of determining cerebrospinal
fluid (CSF) interleukin-6 (IL-6) concentration in adults with purulent, bacterial
meningoencephalitis. MATERIALAND METHODS: A study group consisted of 16 patients
hospitalized in the Department of Infectious Diseases of the Medical University
of Silesia in Bytom in 2008 - 2012 due to purulent, bacterial
meningoencephalitis. All of them were classified into two groups based on
clinical severity, assessed on admission: group I - severe condition, group II -
moderately severe or mild condition. CSF IL-6 concentration was measured in all
patients on the first day of hospitalization. RESULTS: Mean concentrations of IL
6 in CSF were assessed at 391.54 pg/mL and 110.51 pg/mL in patients in severe
(group I) and moderately severe or mild condition (group II), respectively.
Differences between CSF mean concentrations of this cytokine in both groups were
statistically significant (p<0.01). No correlations between CSF IL-6
concentrations and other CSF inflammatory parameters were determined. Control
testing performed in 5 patients of group I revealed only slight decrease of CSF
IL-6 concentration in fatal cases. In case of patients who recovered from
disease, IL-6 concentration in CSF was evidently decreased compared to its
initial value. CONCLUSIONS: Results suggest the usefulness of determining CSF
interleukin-6 concentration to estimate inflammation intensity in the
subarachnoid space, and indirectly, patient's clinical severity. IL-6
concentration may be also of prognostic importance in purulent, bacterial
meningoencephalitis.
PMID- 25848785
TI - Imported cases of dengue in Poland and their diagnosis.
AB - Infections with dengue virus are transmitted by mosquitoes. In tropical areas, it
is mainly spread by Aedes aegypti while in countries with lower temperatures by
Aedes albopictus. Since 2010, autochthonous cases of dengue are also reported in
Europe. There are 4 serotypes of dengue virus (DENV). No correlation between
clinical presentation of disease and virus type, however, were determined.
Nevertheless, reinfection with different type of DENV may lead to a serious, life
threatening condition. An estimated 100 million persons are infected with dengue
virus per year. Of them, approximately a half (mainly children) develop the
symptoms of dengue fever (DF), dengue haemorrhagic fever (DHF) or dengue shock
syndrome (DSS). Fatality is high in case of severe dengue. Dengue is a serious
condition provided there is a presence of IgG antibodies directed against
antigens of particular DENV serotypes, associated with primary infection caused
by different serotype or transferred from infected mother to her child. For
adequate dengue laboratory diagnosis, it is required to apply a set of various
diagnostic methods. Within the family Flaviviridae, cross-reactivity is reported,
which may lead to the occurrence of false-positive results. In Poland,
differential diagnosis with different Flavivirus species is of special importance
as it is an endemic area for tick-borne encephalitis (TBE). Thus, data regarding
history of patient's immunization against TBE or yellow fever should be also
taken into consideration as important in interpretation of results of serological
examination.
PMID- 25848786
TI - Retrospective review of the case of cutaneous anthrax-malignant pustule from 1995
in 15-year old girl.
AB - A 15-year-old girl was admitted to our Department with cutaneous lesion
resembling black eschar. Anamnesis revealed that before getting ill she was
wearing pullover made of rough sheep's wool and ornaments made of leather like
straps. Cutaneous anthrax was confirmed by identification of B. anthracis in
specimens from weeping ulceration, culture from black eschar, thermoprecipitation
test, and bioassay on guinea pig. The girl was treated with crystalline
Penicillin. She responded well to the therapy and recovered after 28 days. What
attracts attention in presented case is the fact that the girl didn't belong to
high risk group of human anthrax, which might lead to misdiagnosis. In 1990-1999,
Poland there were reported 22 cases of anthrax - it was almost exclusively
cutaneous form. In the years following 1999 antrax was reported even less often -
in the period 1991-2013 it was recorded a total of 26 cutaneous anthrax cases.
PMID- 25848787
TI - Prevalence of gastrointestinal system infections acquired in Provincial Hospital
in 2004-2013.
AB - INTRODUCTION: Gastrointestinal system infection (GI) is an infection which is
frequently acquired in health- care settings. In Poland, there are limited data
on the distribution of gastrointestinal system infections in the epidemiology of
healthcare-associated infections (HAIs). Therefore, a study was initiated with
the objective to assess the prevalence and distribution of healthcare-associated
gastrointestinal system infections in patients hospitalized in St. Lukas
Provincial Hospital in Tarnow. MATERIALAND METHODS: Data of 297,545 patients
hospitalized in 2004-2013 were subject to analysis. Standard epidemiological
methods and unified definitions of healthcare-associated infections issued by the
European Centre for Disease Prevention and Control (ECDC) were employed in the
analysis. RESULTS: A total of 944 healthcare-associated gastrointestinal system
infections were indentified in the material analyzed. In a 10-year observation of
HAI prevalence, GIs predominated over other HAIs registered in St. Lukas
Provincial Hospital in Tarnow. Cumulative incidence rate (CIR) and incidence
density rate (IDR) for GIs were 0.35% and 0.57/1,000 person-days, respectively.
Infections with Clostridium difficile (GI-CDI), also referred to as C. difficile
associated diarrhoea (CDAD) were diagnosed in 301 patients. For GI-CDI, CIR and
IDR were 0.11% and 0.18/1,000 person-days, respectively. Gastroenteritis
excluding CDI (GI-GE) was identified in 643 patients with CIR and IDR amounting
to 0.24% and 0.39/1,000 person-days, respectively. Gastroenteritis of rotavirus
(CIR - 0.11% and IDR - 0.18/1,000), adenovirus (CIR - 0.01% and IDR - 0.02/1,000)
and norovirus (CIR - 0.01% and IDR - 0.01/1,000) etiology was identified in 292,
32 and 17 patients, respectively. The highest number of infections was reported
in paediatric ward, i.e. 307 persons (32.5%) (CIR - 1.84% and IDR - 2.79/1,000)
and internal medicine and nephrology ward - 202 infections (21.4%) (CIR - 1.47%
and IDR - 1.66/1,000). CONCLUSIONS: A 10-year observation of healthcare
associated infections showed a change in the distribution of HAIs. In recent
years, GIs predominated over all infections acquired in healthcare settings. The
most prevalent etiological agent identified was Clostridium difficile.
PMID- 25848788
TI - Three-step diagnostic algorithm in diagnosing patients suspected of Clostridium
difficile-associated diarrhea.
AB - Clostridium difficile is a predominant etiological agent of healthcare-associated
infectious diarrhea. Immunoenzymatic tests for detecting toxins A/B from faecal
samples are still used in routine diagnosis of Clostridium difficile-associated
diseases in a number of healthcare centers in Poland. Recently, however, new
diagnostic tests were introduced which allow for detecting toxigenic strains of
C. difficile in a more effective and precise manner. It is of importance,
especially in the light of hypervirulent strain occurrence. AIM: The aim of the
present paper was to evaluate the efficacy of three-step algorithm in the
diagnosis of Clostridium difficile-associated diseases (CDAD), considering the
occurrence of false negative test results for toxins while using exclusively
immunoenzymatic tests. MATERIALS AND METHODS: In the present study, faecal
samples collected from patients presenting diarrhea were tested. Immunoenzymatic
tests were used for detecting glutamate dehydrogenase (GDH) and toxins A/B.
Culture and RT-PCR were also employed. RESULTS: Of 615 study participants,
toxigenic strains GDH (+) TOX (+) were identified in 108 patients while for 67
patients, test results remained unspecified GDH (+) TOX (-). Further analysis of
unspecified samples revealed 32 patients infected with toxigenic strains, i.e.
22.9% of all positive test results (n=140). CONCLUSION: Three-step diagnostic
algorithm is an effective and reliable tool for diagnosing C.difficile-
associated diseases.
PMID- 25848789
TI - Perinatal mortality in urban and rural areas in Poland in 2002-2012.
AB - AIM: The aim of this study was to analyze the level and trends of perinatal
mortality by mother's place of residence (urban vs rural area) in Poland in 2002
2012. MATERIAL AND METHOD: This study was based on the data of the Central
Statistical Office on the number of live births, infant deaths (0-6 days) and
stillbirths by mother's place of residence (urban vs rural area), reported in
2002-2012 in 16 provinces and Poland in general. Joinpoint model was used to
analyze perinatal mortality rate trends over time and average annual percent
change (APC). Urban/rural ratio was employed to demonstrate the differences in
perinatal mortality between urban and rural areas. RESULTS: In the period
analyzed, perinatal mortality in Poland decreased by 3.4% (p<0.05) and 2.7%
(p<0.05) per year in urban and rural areas, respectively. Having considered urban
areas, perinatal mortality rate was decreasing at the fastest pace in the
following provinces: Pomorskie (APC) = -6.6%, p<0.05), Warminsko-Mazurskie (APC)
= -5.4%, p<0.05), Lubuskie i Swietokrzyskie (APC = -4.5%, p<0.05) while for rural
areas - Dolnoslaskie (APC = -4.3%, p<0.05), Wielkopolskie, Zachodniopomorskie
(APC = -3.7%, p<0.05) and Slaskie (APC = -3.2%, p<0.05). CONCLUSIONS: In the
study period, a decrease in perinatal mortality was reported in Poland, both in
urban and rural areas. The level of perinatal mortality rate as well as the pace
of these changes differed between provinces.
PMID- 25848790
TI - Impact of biodiversity on tick-borne diseases.
AB - It is a well-known fact that high biodiversity is related to the health and
proper functioning of environment. Recently, the attempts to search the relations
between biodiversity and human health are also undertaken. A number of studies
demonstrate that people living in undegraded environment are less exposed to the
diseases of affluence. However, they are at a higher risk of contracting
zoonoses. It is believed that the higher the number of animals, the higher is the
number of ticks. Consequently, there is a serious risk of borreliosis and other
tick-borne diseases. Such assumption, however, may be erroneous. A number of
studies suggest a decreasing prevalence of tick-borne disease pathogens in high
biodiversity areas. In this paper, a promising hypothesis explaining this
relation is discussed.
PMID- 25848791
TI - Emergent management of scorpion sting.
AB - Scorpionism (syndrome of scorpion stings) is an important public health problem
in many regions of the world, not only in tropics and subtropics. As scorpions
may be unintentionally transported to any place in the world and keeping
scorpions as pets is becoming more popular, scorpion stings occur also in Poland.
Therefore, health professionals should have the knowledge on the management of
scorpion stings. This article discusses a case who was stung by scorpion and
proposes an algorithm of management with such patients.
PMID- 25848792
TI - Prevalence of dental erosion in young adults aged 18 years in Poland.
AB - AIM: The aim of this study was to assess the prevalence of tooth wear in young
adults in Poland. METHODS: A total of 1,886 persons aged 18 years, selected on a
basis of multistage sampling, were examined within the Nationwide Dental Health
Monitoring Programme. Previously calibrated dentists measured tooth wear using
the BEWE-scoring system (Basic Erosive Wear Examination). RESULTS: Out of 1,886
young adults, 42.2% presented the signs of dental erosion. Considered the
severity of erosion, it was graded as 1, 2 and 3 in 28.9%, 11.9% and 1.5% of 18
year-olds, respectively. CONCLUSIONS: Results of clinical assessment of dental
erosion in 18-year-old young adults revealed that erosive tooth wear is an
important problem in this age group. Of them, 13.4% had signs of advanced tooth
wear which may lead to serious clinical problems in the future.
PMID- 25848793
TI - Ludwik Hirszfeld in the National Institute of Hygiene in 1920-1941.
AB - In this year, we commemorate the 130th anniversary of birth and 60th of death of
Ludwik Hirszfeld, a prominent Polish scientist. Since 1920, he was the head of
the Department of Bacteriology and Experimental Therapy of the National Institute
of Hygiene (NIH). During the absence of Ludwik Rajchman in Poland, who was
assigned to the League of Nations, he was a factual director of the NIH. Ludwik
Hirszfeld governed the scientific, organizational and didactic activities in the
Institute. Concurrently, he collaborated with research centres abroad, especially
within the field of public health. Mission of the NIH was concentrated on a
broadly defined issues aimed at combating infectious diseases, initiating and
developing the production of sera and vaccines, their controlling and introducing
to the country as well as training health care personnel.
PMID- 25848794
TI - Coordination of public institution response to a threat of epidemic.
AB - Workshop held in the National Institute of Public Health - National Institute of
Hygiene on 11th September 2014.
PMID- 25848796
TI - Correction: Incorporating cold-air pooling into downscaled climate models
increases potential refugia for snow-dependent species within the Sierra Nevada
Ecoregion, CA.
PMID- 25848795
TI - Metabolic hormones, apolipoproteins, adipokines, and cytokines in the alveolar
lining fluid of healthy adults: compartmentalization and physiological
correlates.
AB - OBJECTIVES: Our current understanding of hormone regulation in lung parenchyma is
quite limited. We aimed to quantify a diverse array of biologically relevant
protein mediators in alveolar lining fluid (ALF), compared to serum
concentrations, and explore factors associated with protein compartmentalization
on either side of the air-blood barrier. RESEARCH DESIGN AND METHODS:
Participants were 24 healthy adult non-smoker volunteers without respiratory
symptoms or significant medical conditions, with normal lung exams and office
spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24
proteins (including enteric and metabolic hormones, apolipoproteins, adipokines,
and cytokines) using a highly sensitive multiplex ELISA. Measurements were
normalized to ALF concentrations. The ALF:serum concentration ratios were
examined in relation to measures of protein size, hydrophobicity, charge, and to
participant clinical and spirometric values. RESULTS: ALF measurements from 24
individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA
II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent
insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, insulin,
leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1,
resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any
individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or
serum for any individual. In general, ALF levels were similar or lower in
concentration for most proteins compared to serum. However, ghrelin, resistin,
insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared
to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and
resistin correlated with protein net charge and isoelectric point, but not with
molecular weight or hydrophobicity. CONCLUSIONS: Biologically relevant enteric
and metabolic hormones, apolipoproteins, adipokines, and cytokines can be
detected in the ALF of healthy individuals. For the proteins measured, charge may
influence trafficking and compartmentalization to the alveolar airspace more than
molecular weight or hydrophobicity. These data may have implications for
homeostasis and drug delivery to the lung.
PMID- 25848797
TI - Cullin3-BTB interface: a novel target for stapled peptides.
AB - Cullin3 (Cul3), a key factor of protein ubiquitination, is able to interact with
dozens of different proteins containing a BTB (Bric-a-brac, Tramtrack and Broad
Complex) domain. We here targeted the Cul3-BTB interface by using the intriguing
approach of stabilizing the alpha-helical conformation of Cul3-based peptides
through the "stapling" with a hydrocarbon cross-linker. In particular, by
combining theoretical and experimental techniques, we designed and characterized
stapled Cul3-based peptides embedding the helix 2 of the protein (residues 49
68). Intriguingly, CD and NMR experiments demonstrate that these stapled peptides
were able to adopt the helical structure that the fragment assumes in the parent
protein. We also show that some of these peptides were able to bind to the BTB of
the tetrameric KCTD11, a substrate adaptor involved in HDAC1 degradation, with
high affinity (~ 300-600 nM). Cul3-derived staple peptides are also able to bind
the BTB of the pentameric KCTD5. Interestingly, the affinity of these peptides is
of the same order of magnitude of that reported for the interaction of full
length Cul3 with some BTB containing proteins. Moreover, present data indicate
that stapling endows these peptides with an increased serum stability.
Altogether, these findings indicate that the designed stapled peptides can
efficiently mimic protein-protein interactions and are potentially able to
modulate fundamental biological processes involving Cul3.
PMID- 25848799
TI - Receding water line and interspecific competition determines plant community
composition and diversity in wetlands in Beijing.
AB - Climate and human-induced wetland degradation has accelerated in recent years,
not only resulting in reduced ecosystem services but also greatly affecting the
composition and diversity of wetland plant communities. To date, the knowledge of
the differences in community parameters and their successional trends in degraded
wetlands remains scarce. Here based on remote sensing images, geographic
information system technology, and statistical methods, we produced a
successional gradient map of the Yeyahu Wetland Nature Reserve in Beijing, which
has experienced a steady decline in water level in recent decades. In addition,
we analyzed community composition and diversity along with each identified
gradient. The results showed that community diversity decreases while dominance
increases with the progress of succession, with the highest diversity occurring
during the early stage of succession. Moreover, the community demonstrates
greater similarity among subareas during later successional stages, and the
similarity coefficients calculated from the important value (IV) of each species
are more accurate. Correlation analysis showed that the impact of soil factors on
diversity was not significant at a subarea scale, although these nutrients showed
an increasing trend with the community succession. Furthermore, the IVs of the
dominant species had a particularly significant impact on diversity, showing a
significantly negative correlation with diversity indices and a significantly
positive correlation with dominance indices. Further analysis showed that the
retreat of water level resulted from sustained drought and local human activities
was a major extrinsic driving force resulting in observed differences in the
community successional stages, which resulted in differences in community
composition and diversity. On the other hand, interspecific competition was the
main intrinsic mechanism, which significantly influenced the IVs of the dominant
species and community diversity. The results of this study could aid in improving
the understanding of community composition, diversity, and its successional
trends in degraded wetlands.
PMID- 25848798
TI - Shigella infection interferes with SUMOylation and increases PML-NB number.
AB - Shigellosis is a severe diarrheal disease that affects hundreds of thousands of
individuals resulting in significant morbidity and mortality worldwide.
Shigellosis is caused by Shigella spp., a gram-negative bacterium that uses a
Type 3 Secretion System (T3SS) to deliver effector proteins into the cytosol of
infected human cells. Shigella infection triggers multiple signaling programs
that result in a robust host transcriptional response that includes the induction
of multiple proinflammatory cytokines. PML nuclear bodies (PML-NBs) are dynamic
subnuclear structures that coordinate immune signaling programs and have a
demonstrated role in controlling viral infection. We show that PML-NB number
increases upon Shigella infection. We examined the effects of Shigella infection
on SUMOylation and found that upon Shigella infection the localization of
SUMOylated proteins is altered and the level of SUMOylated proteins decreases.
Although Shigella infection does not alter the abundance of SUMO activating
enzymes SAE1 or SAE2, it dramatically decreases the level of the SUMO conjugating
enzyme Ubc9. All Shigella-induced alterations to the SUMOylation system are
dependent upon a T3SS. Thus, we demonstrate that Shigella uses one or more T3SS
effectors to influence both PML-NB number and the SUMOylation machinery in human
cells.
PMID- 25848800
TI - Unlocking patients with mental disorders who were in restraints at home: a
national follow-up study of China's new public mental health initiatives.
AB - BACKGROUND: In 2005, China implemented a demonstration program known as "686" to
scale-up nation-wide basic mental health services designed to improve access to
evidence-based care and to promote human rights for people with severe mental
disorders. As part of the 686 Program, teams "unlocked" and provided continuous
mental health care to people with severe mental disorders who were found in
restraints and largely untreated in their family homes. We implemented a nation
wide two-stage follow-up study to measure the effectiveness and sustainability of
the "unlocking and treatment" intervention and its impact on the well-being of
patients' families. METHODS: 266 patients unlocked from 2005 in "686"
demonstration sites across China were recruited in Stage One of the study in
2009. In 2012, 230 of the 266 cases were re-interviewed (the Stage Two study).
Outcome measures included the patient medication adherence and social
functioning, family burden ratings, and relocking rate. We utilized pre-post
tests to analyze the changes over time following the unlocking efforts. RESULTS:
96% of patients were diagnosed with schizophrenia. Prior to unlocking, their
total time locked ranged from two weeks to 28 years, with 32% having been locked
multiple times. The number of persons regularly taking medicines increased from
one person at the time of unlocking to 74% in 2009 and 76% in 2012. Pre-post
tests showed sustained improvement in patient social functioning and significant
reductions in family burden. Over 92% of patients remained free of restraints in
2012. CONCLUSION: Practice-based evidence from our study suggests an important
model for protecting the human rights of people with mental disorders and keeping
them free of restraints can be achieved by providing accessible, community based
mental health services with continuity of care. China's "686" Program can inform
similar efforts in low-resource settings where community locking of patients is
practiced.
PMID- 25848801
TI - Human Pirh2 is a novel inhibitor of prototype foamy virus replication.
AB - Prototype foamy virus (PFV) is a member of the unconventional and nonpathogenic
retroviruses. PFV causes lifelong chronic infections, which are partially
attributable to a number of host cell factors that restrict viral replication.
Herein, we identified human p53-induced RING-H2 protein (Pirh2) as a novel
inhibitor of prototype foamy virus. Overexpression of Pirh2 decreased the
replication of PFV, whereas knockdown of Pirh2 with specific siRNA increased PFV
replication. Dual-luciferase assays and coimmunoprecipitation demonstrated that
Pirh2 negatively influences the Tas-dependent transcriptional activation of the
PFV long terminal repeat (LTR) and internal promoter (IP) by interacting with the
transactivator Tas and down-regulating its expression. In addition, the viral
inhibitory function of Pirh2 is N-terminal and RING domain dependent. Together,
these results indicated that Pirh2 suppresses PFV replication by negatively
impacting its transactivator Tas and the transcription of two viral promoters,
which may contribute to the latency of PFV infection.
PMID- 25848802
TI - Pulmonary rehabilitation in Canada: A report from the Canadian Thoracic Society
COPD Clinical Assembly.
AB - BACKGROUND: Pulmonary rehabilitation (PR) is a recommended intervention in the
management of individuals with chronic lung disease. It is important to study the
characteristics and capacity of programs in Canada to confirm best practices and
identify future areas of program improvement and research. OBJECTIVE: To identify
all Canadian PR programs, regardless of setting, and to comprehensively describe
all aspects of PR program delivery. The present article reports the results of
the survey related to type of program, capacity and program characteristics.
METHODS: All hospitals in Canada were contacted to identify PR programs. A
representative from each program completed a 175-item online survey encompassing
16 domains, 10 of which are reported in the present article. RESULTS: A total of
155 facilities in Canada offered PR, of which 129 returned surveys (83% response
rate). PR programs were located in all provinces, but none in the three
territories. Most (60%) programs were located in hospital settings, 24% were in
public health units and 8% in recreation centres. The national capacity of
programs was estimated to be 10,280 patients per year, resulting in 0.4% of all
Canadians with chronic obstructive pulmonary disease (COPD) and 0.8% of Canadians
with moderate to severe COPD having access to PR. COPD, interstitial lung
disease, and asthma were the most common diagnoses of patients. The majority of
programs had at least four health care professionals involved; 9% had only one
health care professional involved. CONCLUSION: The present comprehensive survey
of PR in Canada reports an increase in the number of programs and the total
number of patients enrolled since the previous survey in 2005. However, PR
capacity has not kept pace with demand, with only 0.4% of Canadians with COPD
having access.
PMID- 25848803
TI - Surgical versus nonsurgical interventions to relieve upper airway obstruction in
children with Pierre Robin sequence.
AB - BACKGROUND: Newborns with Pierre Robin sequence (PRS) often experience chronic
intermittent hypoxemia/hypoventilation associated with airway obstruction. The
heterogeneity of the severity of upper airway obstruction makes management a
challenge; the optimal intervention in individual cases is not clear. OBJECTIVE:
To investigate the prevalence of surgical/nonsurgical interventions for PRS at
two children's hospitals. Patient characteristics and outcomes were examined.
METHODS: The present retrospective chart review identified 139 patients with PRS
born between 2000 and 2010. Demographic information, mode of airway management,
associated anomalies and syndromes, polysomnography results, length of intensive
care unit and hospital stay, complications and deaths were extracted. RESULTS:
Interventions included prone positioning (alone [61%]), tongue-lip adhesion
(45%), nasopharyngeal intubation (28%), continuous positive airway pressure
(20%), tracheostomy (19%) and mandibular distraction osteogenesis (5%).
Tracheostomies were more prevalent in syndromic patients (P=0.03). Patients who
underwent tracheostomy had a lower birth weight (P=0.03) compared with newborns
with other interventions. Patients who underwent surgical interventions had
longer intensive care unit stays (P<0.001). No intervention was associated with a
statistically significant likelihood of requiring a subsequent intervention.
Thirty percent of patients underwent polysomnography, with a higher proportion of
these using continuous positive airway pressure (n=15) (P<0.01). CONCLUSIONS: In
the present descriptive study, patients with syndromic PRS or low birth weight
underwent early intervention, which included a tracheostomy. Objective measures
of airway obstruction were underutilized. Decision making regarding evaluation
and management of upper airway obstruction in this population remains clinician
and resource dependent. Reporting data obtained from a large cohort of PRS
patients is important to compare experiences and motivate future studies
investigating this complex condition.
PMID- 25848804
TI - Relationship Between Fatigue and Changes in Swim Technique During an Exhaustive
Swim Exercise.
AB - PURPOSE: To analyze the relationship between the responses of isometric peak
torque (IPT) and maximal rate of force development (RFDmax) with the changes in
stroking parameters in an exhaustive exercise performed in front crawl. METHODS:
Fifteen male swimmers performed, on different days, the following protocols:
maximal 400-m trial, strength tests before and after an exhaustive test at 100%
of the mean speed obtained during the 400-m test, and the same procedures on day
2. RESULTS: The IPT of elbow flexors (79.9 +/- 19.4 and 66.7 +/- 20.0 N.m) and
elbow extensors (95.1 +/- 28.0 N.m and 85.8 +/- 30.5 N.m) was decreased after the
swim test, as was RFDmax (521.8 +/- 198.6 and 426.0 +/- 229.9 N.m/s; 420.6 +/-
168.2 and 384.0 +/- 143.5 N.m/s, respectively). Stroke length decreased during
the swim test (1.96 +/- 0.22 and 1.68 +/- 0.29 m/stroke), while stroke rate
increased (37.2 +/- 3.14 and 41.3 +/- 4.32 strokes/min). The propulsive phases
increased while the nonpropulsive phases decreased during the test. Significant
correlation was found between the changes in IPT and stroke length, stroke rate
and recovery (elbow flexors), and entry and catch phase (elbow extensors). In
addition, significant correlation was found between the changes in RFDmax of
elbow flexors with the changes in pull and recovery phases. CONCLUSION: Changes
in swim technique during an exhaustive test can be, at least in part, associated
with fatigue of the arm muscles.
PMID- 25848805
TI - Different Raman spectral patterns of primary rat pancreatic beta cells and
insulinoma cells.
AB - As a noninvasive and label-free analytical technique, Raman spectroscopy has been
widely used to study the difference between malignant cells and normal cells.
Insulinomas are functional beta-cell tumors of pancreatic islet cells. They
exhibit many structural and immunohistochemical features in common with normal
pancreatic beta cells; thus, they are typically difficult to distinguish under
the microscope, especially in vivo. We investigated insulinoma and primary rat
pancreatic beta-cell populations using Raman spectroscopy. The details of the
optical heterogeneity between these two populations were determined based on
different Raman regions primarily involving nucleic acid and protein contents,
which are the most distinct cellular contents in these two types of cells. Using
principal component analysis-linear discriminant analysis, these two cell types
can be readily separated. The results of this work indicate that Raman
spectroscopy is a promising tool for the noninvasive and label-free
differentiation of insulinoma cells and normal pancreatic beta cells.
PMID- 25848806
TI - Regeneration of Light-Harvesting Complexes via Dynamic Replacement of
Photodegraded Chromophores.
AB - All-synthetic molecular donor-acceptor complexes are designed, which are capable
of counteracting the effect of photoinduced degradation of donor chromophores.
Anionic gallium protoporphyrin IX (GaPP) and semiconducting carbon nanotube (CNT)
are used as a model donor-acceptor complex, which is assembled using DNA
oligonucleotides. The GaPP-DNA-CNT complex produces an anodic photocurrent in a
photoelectrochemical cell, which steadily decays due to photo-oxidation. By
modulating the chemical environment, we showed that the photodegraded
chromophores may be dissociated from the complex, whereas the DNA-coated carbon
nanotube acceptors are kept intact. Reassociation with fresh porphyrins leads to
the full recovery of GaPP absorption and photocurrents. This strategy could form
a basis for improving the light-harvesting performance of molecular donor
acceptor complexes and extending their operation lifetime.
PMID- 25848807
TI - Lipopolysaccharide perception leads to dynamic alterations in the
microtranscriptome of Arabidopsis thaliana cells and leaf tissues.
AB - BACKGROUND: MicroRNAs (miRNAs) are non-coding RNA molecules which have recently
emerged as important gene regulators in plants and their gene expression analysis
is becoming increasingly important. miRNAs regulate gene expression at the post
transcriptional level by translational repression or target degradation of
specific mRNAs and gene silencing. In order to profile the microtranscriptome of
Arabidopsis thaliana leaf and callus tissues in response to bacterial
lipopolysaccharide (LPS), small RNA libraries were constructed at 0 and 3 h post
induction with LPS and sequenced by Illumina sequencing technology. RESULTS:
Differential regulation of subset of miRNAs in response to LPS treament was
observed. Small RNA reads were mapped to the miRNA database and 358 miRNAs
belonging to 49 miRNA families in the callus tissues and 272 miRNAs belonging to
40 miRNA families in the leaf tissues were identified. Moreover, target genes for
all the identified miRNAs families in the leaf tissues and 44 of the 49 miRNAs
families in the callus tissues were predicted. The sequencing analysis showed
that in both callus and leaf tissues, various stress regulated-miRNAs were
differentially expressed and real time PCR validated the expression profile of
miR156, miR158, miR159, miR169, miR393, miR398, miR399 and miR408 along with
their target genes. CONCLUSION: A. thaliana callus and leaf callus tissues
respond to LPS as a microbe-associated molecular pattern molecule through dynamic
changes to the microtranscriptome associated with differential transcriptional
regulation in support of immunity and basal resistance.
PMID- 25848808
TI - Nanowire-bacteria hybrids for unassisted solar carbon dioxide fixation to value
added chemicals.
AB - Direct solar-powered production of value-added chemicals from CO2 and H2O, a
process that mimics natural photosynthesis, is of fundamental and practical
interest. In natural photosynthesis, CO2 is first reduced to common biochemical
building blocks using solar energy, which are subsequently used for the synthesis
of the complex mixture of molecular products that form biomass. Here we report an
artificial photosynthetic scheme that functions via a similar two-step process by
developing a biocompatible light-capturing nanowire array that enables a direct
interface with microbial systems. As a proof of principle, we demonstrate that a
hybrid semiconductor nanowire-bacteria system can reduce CO2 at neutral pH to a
wide array of chemical targets, such as fuels, polymers, and complex
pharmaceutical precursors, using only solar energy input. The high-surface-area
silicon nanowire array harvests light energy to provide reducing equivalents to
the anaerobic bacterium, Sporomusa ovata, for the photoelectrochemical production
of acetic acid under aerobic conditions (21% O2) with low overpotential (eta <
200 mV), high Faradaic efficiency (up to 90%), and long-term stability (up to 200
h). The resulting acetate (~6 g/L) can be activated to acetyl coenzyme A (acetyl
CoA) by genetically engineered Escherichia coli and used as a building block for
a variety of value-added chemicals, such as n-butanol, polyhydroxybutyrate (PHB)
polymer, and three different isoprenoid natural products. As such, interfacing
biocompatible solid-state nanodevices with living systems provides a starting
point for developing a programmable system of chemical synthesis entirely powered
by sunlight.
PMID- 25848809
TI - Satisfaction with local exercise facility: a rural-urban comparison in China.
AB - INTRODUCTION: Rural-urban inequalities in China have been widening over the past
few decades. Compared to their urban counterparts, rural residents may encounter
various barriers to equal opportunities to effectively engage in physical
activity. This study examines the rural-urban disparity in physical activity,
proximity and satisfaction with local exercise facilities. METHODS: An in-person
survey was conducted in 29 counties of 10 Chinese provinces in 2012. Five
thousand questionnaires were administered by trained staff with a completion rate
of 82.1%. The complete sample includes 1661 rural and 2446 urban residents. Eight
dichotomous outcome measures were used, pertaining to leisure-time physical
activity engagement; proximity to the nearest exercise facility from home;
satisfaction level with the quantity, variety, fee levels, opening hours, and
daily management and services of nearby exercise facilities; and satisfaction
level with the local public sports service system. Nearest-neighbor matching was
performed to match rural residents with urban residents by observed individual
sociodemographics, including gender, age, education level and residential
province. Pearson's chi2 test was used to assess the difference in
sociodemographics and outcome measures between rural and urban residents before
and after matching. RESULTS: Before nearest-neighbor matching, the frequency
distributions of age and education level are significantly different between
rural and urban residents (both p<0.0001). After matching, the differences in the
frequency distributions between rural and urban residents become statistically
non-significant for all observed sociodemographics: gender (p=0.170), age
(p=0.934), education level (p=0.244) and residential province (p=1.000). Compared
to their matched urban counterparts, rural residents are 8.1% (p<0.0001) more
likely to be physically inactive in their leisure time and 5.8% (p=0.005) less
likely to live within 30-minute walking distance to the nearest exercise
facility. Rural residents are 15.7%, 15.7%, 8.6%, 13.5% and 14.7% more likely to
be unsatisfied with the quantity, variety, fee levels, opening hours, and daily
management and services of nearby exercise facilities, and 16.1% more likely to
be unsatisfied with the local public sports service system than matched urban
residents (all p<0.0001). CONCLUSIONS: Substantial rural-urban disparities tend
to be present in leisure-time physical activity, proximity to the nearest
exercise facility, and satisfaction level with exercise facilities and the public
sports service system. Policy interventions are warranted to improve the
accessibility and affordability of local exercise facilities in rural areas as a
way to promote physical activity among Chinese rural residents and reduce
disparities.
PMID- 25848811
TI - Transition States and transition state analogue interactions with enzymes.
AB - Enzymatic transition states have lifetimes of a few femtoseconds (fs).
Computational analysis of enzyme motions leading to transition state formation
suggests that local catalytic site motions on the fs time scale provide the
mechanism to locate transition states. An experimental test of protein fs motion
and its relation to transition state formation can be provided by isotopically
heavy proteins. Heavy enzymes have predictable mass-altered bond vibration states
without altered electrostatic properties, according to the Born-Oppenheimer
approximation. On-enzyme chemistry is slowed in most heavy proteins, consistent
with altered protein bond frequencies slowing the search for the transition
state. In other heavy enzymes, structural changes involved in reactant binding
and release are also influenced. Slow protein motions associated with substrate
binding and catalytic site preorganization are essential to allow the subsequent
fs motions to locate the transition state and to facilitate the efficient release
of products. In the catalytically competent geometry, local groups move in
stochastic atomic motion on the fs time scale, within transition state-accessible
conformations created by slower protein motions. The fs time scale for the
transition state motions does not permit thermodynamic equilibrium between the
transition state and stable enzyme states. Isotopically heavy enzymes provide a
diagnostic tool for fast coupled protein motions to transition state formation
and mass-dependent conformational changes. The binding of transition state
analogue inhibitors is the opposite in catalytic time scale to formation of the
transition state but is related by similar geometries of the enzyme-transition
state and enzyme-inhibitor interactions. While enzymatic transition states have
lifetimes as short as 10(-15) s, transition state analogues can bind tightly to
enzymes with release rates greater than 10(3) s. Tight-binding transition state
analogues stabilize the rare but evolved enzymatic geometry to form the
transition state. Evolution to efficient catalysis optimized this geometry and
its stabilization by a transition state mimic results in tight binding. Release
rates of transition state analogues are orders of magnitude slower than product
release in normal catalytic function. During catalysis, product release is
facilitated by altered chemistry. Compared to the weak associations found in
Michaelis complexes, transition state analogues involve strong interactions
related to those in the transition state. Optimum binding of transition state
analogues occurs when the complex retains the system motions intrinsic to
transition state formation. Conserved dynamic motion retains the entropic
components of inhibitor complexes, improving the thermodynamics of analogue
binding.
PMID- 25848810
TI - High-throughput deep sequencing reveals that microRNAs play important roles in
salt tolerance of euhalophyte Salicornia europaea.
AB - BACKGROUND: microRNAs (miRNAs) are implicated in plant development processes and
play pivotal roles in plant adaptation to environmental stresses. Salicornia
europaea, a salt mash euhalophyte, is a suitable model plant to study salt
adaptation mechanisms. S. europaea is also a vegetable, forage, and oilseed that
can be used for saline land reclamation and biofuel precursor production on
marginal lands. Despite its importance, no miRNA has been identified from S.
europaea thus far. RESULTS: Deep sequencing was performed to investigate small
RNA transcriptome of S. europaea. Two hundred and ten conserved miRNAs comprising
51 families and 31 novel miRNAs (including seven miRNA star sequences) belonging
to 30 families were identified. About half (13 out of 31) of the novel miRNAs
were only detected in salt-treated samples. The expression of 43 conserved and 13
novel miRNAs significantly changed in response to salinity. In addition, 53
conserved and 13 novel miRNAs were differentially expressed between the shoots
and roots. Furthermore, 306 and 195 S. europaea unigenes were predicted to be
targets of 41 conserved and 29 novel miRNA families, respectively. These targets
encoded a wide range of proteins, and genes involved in transcription regulation
constituted the largest category. Four of these genes encoding laccase, F-box
family protein, SAC3/GANP family protein, and NADPH cytochrome P-450 reductase
were validated using 5'-RACE. CONCLUSIONS: Our results indicate that specific
miRNAs are tightly regulated by salinity in the shoots and/or roots of S.
europaea, which may play important roles in salt tolerance of this euhalophyte.
The S. europaea salt-responsive miRNAs and miRNAs that target transcription
factors, nucleotide binding site-leucine-rich repeat proteins and enzymes
involved in lignin biosynthesis as well as carbon and nitrogen metabolism may be
applied in genetic engineering of crops with high stress tolerance, and genetic
modification of biofuel crops with high biomass and regulatable lignin
biosynthesis.
PMID- 25848812
TI - Towards a physically more active lifestyle based on one's own values: the results
of a randomized controlled trial among physically inactive adults.
AB - BACKGROUND: The high prevalence of physical inactivity has led to a search for
novel and feasible interventions that will enhance physical activity, especially
among the least physically active individuals. This randomized controlled trial
aimed to determine the effectiveness of a value-based intervention to promote a
physically more active lifestyle among physically inactive adults. The framework
of the study was based on Acceptance and Commitment Therapy (ACT). METHODS:
Physically inactive participants aged 30 to 50 years (n = 138) were randomly
allocated to a feedback (FB, n = 69) or an acceptance- and commitment-based group
(ACT + FB, n = 69). Both groups received written feedback about their objectively
measured physical activity and were offered a body composition analysis. In
addition, the participants in the ACT + FB group attended six group sessions and
were given a pedometer for self-monitoring their physical activity during the
nine-week intervention. The primary outcome was physical activity. In addition,
participants' cognitions related to exercise and physical activity were evaluated
at baseline and at three- and six-month follow-ups. The changes in mean physical
activity level were analysed using multilevel random regression and rank order
stability, using the structural equation model. RESULTS: Participants in both
groups increased their objectively measured and self-reported physical activity
with high individual differences. No difference was observed in the change of
physical activity level between the FB and ACT + FB groups over time. However,
the cognitions related to physical activity and exercise improved more in the ACT
+ FB group than in the FB group. In addition, after re-analyzing the data among
the non-depressive participants, higher stability was observed in objectively
measured physical activity at the individual level between the three- and six
month follow-ups in the ACT + FB group as compared to FB group. CONCLUSIONS:
Acceptance- and commitment-based group intervention, combined with the self
monitoring of physical activity, was beneficial in supporting the cognition
related to exercise and physical activity, and brought more stability to the
individual level physical activity behaviour change, especially among the non
depressive participants. TRIAL REGISTRATION: ClinicalTrials.gov, number
NCT01796990. Registered in February 2013.
PMID- 25848813
TI - Population structure and genetic diversity characterization of a sunflower
association mapping population using SSR and SNP markers.
AB - BACKGROUND: Argentina has a long tradition of sunflower breeding, and its
germplasm is a valuable genetic resource worldwide. However, knowledge of the
genetic constitution and variability levels of the Argentinean germplasm is still
scarce, rendering the global map of cultivated sunflower diversity incomplete. In
this study, 42 microsatellite loci and 384 single nucleotide polymorphisms (SNPs)
were used to characterize the first association mapping population used for
quantitative trait loci mapping in sunflower, along with a selection of allied
open-pollinated and composite populations from the germplasm bank of the National
Institute of Agricultural Technology of Argentina. The ability of different kinds
of markers to assess genetic diversity and population structure was also
evaluated. RESULTS: The analysis of polymorphism in the set of sunflower
accessions studied here showed that both the microsatellites and SNP markers were
informative for germplasm characterization, although to different extents. In
general, the estimates of genetic variability were moderate. The average genetic
diversity, as quantified by the expected heterozygosity, was 0.52 for SSR loci
and 0.29 for SNPs. Within SSR markers, those derived from non-coding regions were
able to capture higher levels of diversity than EST-SSR. A significant
correlation was found between SSR and SNP- based genetic distances among
accessions. Bayesian and multivariate methods were used to infer population
structure. Evidence for the existence of three different genetic groups was found
consistently across data sets (i.e., SSR, SNP and SSR + SNP), with the
maintainer/restorer status being the most prevalent characteristic associated
with group delimitation. CONCLUSION: The present study constitutes the first
report comparing the performance of SSR and SNP markers for population genetics
analysis in cultivated sunflower. We show that the SSR and SNP panels examined
here, either used separately or in conjunction, allowed consistent estimations of
genetic diversity and population structure in sunflower breeding materials. The
generated knowledge about the levels of diversity and population structure of
sunflower germplasm is an important contribution to this crop breeding and
conservation.
PMID- 25848814
TI - Rationally Designed MicroRNA-Based Genetic Classifiers Target Specific Neurons in
the Brain.
AB - Targeting transgene expression to specific cell types in vivo has proven
instrumental in characterizing the functional role of defined cell populations.
Genetic classifiers, synthetic transgene constructs designed to restrict
expression to particular classes of cells, commonly rely on transcriptional
promoters to define cellular specificity. However, the large size of many natural
promoters complicates their use in viral vectors, an important mode of transgene
delivery in the brain and in human gene therapy. Here, we expanded upon an
emerging classifier platform, orthogonal to promoter-based strategies, that
exploits endogenous microRNA regulation to target gene expression. Such
classifiers have been extensively explored in other tissues; however, their use
in the nervous system has thus far been limited to targeting gene expression
between neurons and supporting cells. Here, we tested the possibility of using
combinatory microRNA regulation to specify gene targeting between neuronal
subtypes, and successfully targeted inhibitory cells in the neocortex. These
classifiers demonstrate the feasibility of designing a new generation of microRNA
based neuron-type- and brain-region-specific gene expression targeting
neurotechnologies.
PMID- 25848816
TI - Erratum to: "A novel role for ezrin in breast cancer angio/lymphangiogenesis".
PMID- 25848815
TI - Inhibition of HMGCoA reductase by simvastatin protects mice from injurious
mechanical ventilation.
AB - BACKGROUND: Mortality from severe acute respiratory distress syndrome exceeds 40%
and there is no available pharmacologic treatment. Mechanical ventilation
contributes to lung dysfunction and mortality by causing ventilator-induced lung
injury. We explored the utility of simvastatin in a mouse model of severe
ventilator-induced lung injury. METHODS: Male C57BL6 mice (n = 7/group) were
pretreated with simvastatin or saline and received protective (8 mL/kg) or
injurious (25 mL/kg) ventilation for four hours. Three doses of simvastatin (20
mg/kg) or saline were injected intraperitoneally on days -2, -1 and 0 of the
experiment. Lung mechanics, (respiratory system elastance, tissue damping and
airway resistance), were evaluated by forced oscillation technique, while
respiratory system compliance was measured with quasi-static pressure-volume
curves. A pathologist blinded to treatment allocation scored hematoxylin-eosin
stained lung sections for the presence of lung injury. Pulmonary endothelial
dysfunction was ascertained by bronchoalveolar lavage protein content and lung
tissue expression of endothelial junctional protein Vascular Endothelial cadherin
by immunoblotting. To assess the inflammatory response in the lung, we determined
bronchoalveolar lavage fluid total cell content and neutrophil fraction by
microscopy and staining in addition to Matrix-Metalloprotease-9 by ELISA. For the
systemic response, we obtained plasma levels of Tumor Necrosis Factor-alpha,
Interleukin-6 and Matrix-Metalloprotease-9 by ELISA. Statistical hypothesis
testing was undertaken using one-way analysis of variance and Tukey's post hoc
tests. RESULTS: Ventilation with high tidal volume (HVt) resulted in
significantly increased lung elastance by 3-fold and decreased lung compliance by
45% compared to low tidal volume (LVt) but simvastatin abrogated lung mechanical
alterations of HVt. Histologic lung injury score increased four-fold by HVt but
not in simvastatin-pretreated mice. Lavage pleocytosis and neutrophilia were
induced by HVt but were significantly attenuated by simvastatin. Microvascular
protein permeability increase 20-fold by injurious ventilation but only 4-fold
with simvastatin. There was a 3-fold increase in plasma Tumor Necrosis Factor
alpha, a 7-fold increase in plasma Interleukin-6 and a 20-fold increase in lavage
fluid Matrix-Metalloprotease-9 by HVt but simvastatin reduced these levels to
control. Lung tissue vascular endothelial cadherin expression was significantly
reduced by injurious ventilation but remained preserved by simvastatin.
CONCLUSION: High-dose simvastatin prevents experimental hyperinflation lung
injury by angioprotective and anti-inflammatory effects.
PMID- 25848819
TI - Electronic pseudogap-driven formation of new double-perovskite-like borides
within the Sc2Ir6-xTxB (T = Pd, Ni; x = 0-6) series.
AB - Analysis of the electronic density of states of the hypothetical ternary double
perovskite-like phases "Sc2T6B (T = Ir, Pd, Ni)" reveals the presence of deep and
large pseudogaps between 61 and 68 valence electrons (VE) as well as a strong
peak at 69 VEs. Subsequently, crystal orbital Hamilton population (COHP) bonding
analysis shows that the heteroatomic T-B and Sc-T interactions are optimized in
Sc2Ir6B (63 VE) but not in "Sc2Pd6B (69 VE)" and "Sc2Ni6B (69 VE)", thus
indicating less stability for these VE-richer phases. These findings point out
the possibility of discovering new double-perovskite-like borides through
chemical substitution and lead to the study of the Sc2Ir6-xPdxB and Sc2Ir6-xNixB
(x = 0-6; VE = 63-69) series, for which powder samples and single crystals were
synthesized by arc melting the elements. Superstructure reflections were observed
in the powder diffractograms of Sc2Ir6-xPdxB and Sc2Ir6-xNixB for x = 0-5 and VE
= 63-68, thereby showing that these phases crystallize in the double-perovskite
like Ti2Rh6B-type structure (space group Fm3m, Z = 4). Single-crystal and
Rietveld refinement results confirm and extend these findings because Pd (or Ni)
is found to mix exclusively with Ir in all quaternary compositions. For x = 6, no
superstructure reflections were observed, in accordance with the theoretical
expectation for the 69 VE phases.
PMID- 25848818
TI - The contrasting N management of two oilseed rape genotypes reveals the mechanisms
of proteolysis associated with leaf N remobilization and the respective
contributions of leaves and stems to N storage and remobilization during seed
filling.
AB - BACKGROUND: Oilseed rape is the third largest oleaginous crop in the world but
requires high levels of N fertilizer of which only 50% is recovered in seeds.
This weak N use efficiency is associated with a low foliar N remobilization,
leading to a significant return of N to the soil and a risk of pollution.
Contrary to what is observed during senescence in the vegetative stages, N
remobilization from stems and leaves is considered efficient during monocarpic
senescence. However, the contribution of stems towards N management and the
cellular mechanisms involved in foliar remobilization remain largely unknown. To
reach this goal, the N fluxes at the whole plant level from bolting to mature
seeds and the processes involved in leaf N remobilization and proteolysis were
investigated in two contrasting genotypes (Aviso and Oase) cultivated under ample
or restricted nitrate supply. RESULTS: During seed filling in both N conditions,
Oase efficiently allocated the N from uptake to seeds while Aviso favoured a
better N remobilization from stems and leaves towards seeds. Nitrate restriction
decreased seed yield and oil quality for both genotypes but Aviso had the best
seed N filling. Under N limitation, Aviso had a better N remobilization from
leaves to stems before the onset of seed filling. Afterwards, the higher N
remobilization from stems and leaves of Aviso led to a higher final N amount in
seeds. This high leaf N remobilization is associated with a better
degradation/export of insoluble proteins, oligopeptides, nitrate and/or ammonia.
By using an original method based on the determination of Rubisco degradation in
the presence of inhibitors of proteases, efficient proteolysis associated with
cysteine proteases and proteasome activities was identified as the mechanism of N
remobilization. CONCLUSION: The results confirm the importance of foliar N
remobilization after bolting to satisfy seed filling and highlight that an
efficient proteolysis is mainly associated with (i) cysteine proteases and
proteasome activities and (ii) a fine coordination between proteolysis and export
mechanisms. In addition, the stem may act as transient storage organs in the case
of an asynchronism between leaf N remobilization and N demand for seed filling.
PMID- 25848817
TI - Poorly controlled type 2 diabetes is accompanied by significant morphological and
ultrastructural changes in both erythrocytes and in thrombin-generated fibrin:
implications for diagnostics.
AB - We have noted in previous work, in a variety of inflammatory diseases, where iron
dysregulation occurs, a strong tendency for erythrocytes to lose their normal
discoid shape and to adopt a skewed morphology (as judged by their axial ratios
in the light microscope and by their ultrastructure in the SEM). Similarly, the
polymerization of fibrinogen, as induced in vitro by added thrombin, leads not to
the common 'spaghetti-like' structures but to dense matted deposits. Type 2
diabetes is a known inflammatory disease. In the present work, we found that the
axial ratio of the erythrocytes of poorly controlled (as suggested by increased
HbA1c levels) type 2 diabetics was significantly increased, and that their fibrin
morphologies were again highly aberrant. As judged by scanning electron
microscopy and in the atomic force microscope, these could be reversed, to some
degree, by the addition of the iron chelators deferoxamine (DFO) or deferasirox
(DFX). As well as their demonstrated diagnostic significance, these morphological
indicators may have prognostic value.
PMID- 25848820
TI - Prognostic stromal gene signatures in breast cancer.
AB - INTRODUCTION: Global gene expression analysis of tumor samples has been a
valuable tool to subgroup tumors and has the potential to be of prognostic and
predictive value. However, tumors are heterogeneous, and homogenates will consist
of several different cell types. This study was designed to obtain more refined
expression data representing different compartments of the tumor. METHODS:
Formalin-fixed paraffin-embedded stroma-rich triple-negative breast cancer tumors
were laser-microdissected, and RNA was extracted and processed to enable
microarray hybridization. Genes enriched in stroma were identified and used to
generate signatures by identifying correlating genes in publicly available data
sets. The prognostic implications of the signature were analyzed. RESULTS:
Comparison of the expression pattern from stromal and cancer cell compartments
from three tumors revealed a number of genes that were essentially specifically
expressed in the respective compartments. The stroma-specific genes indicated
contribution from fibroblasts, endothelial cells, and immune/inflammatory cells.
The gene set was expanded by identifying correlating mRNAs using breast cancer
mRNA expression data from The Cancer Genome Atlas. By iterative analyses, 16 gene
signatures of highly correlating genes were characterized. Based on the gene
composition, they seem to represent different cell types. In multivariate Cox
proportional hazard models, two immune/inflammatory signatures had opposing
hazard ratios for breast cancer recurrence also after adjusting for
clinicopathological variables and molecular subgroup. The signature associated
with poor prognosis consisted mainly of C1Q genes and the one associated with
good prognosis contained HLA genes. This association with prognosis was seen for
other cancers as well as in other breast cancer data sets. CONCLUSIONS: Our data
indicate that the molecular composition of the immune response in a tumor may be
a powerful predictor of cancer prognosis.
PMID- 25848821
TI - Ni-Catalyzed C-H Functionalization in the Formation of a Complex Heterocycle:
Synthesis of the Potent JAK2 Inhibitor BMS-911543.
AB - BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for
myeloproliferative disorders. The development of a short and efficient synthesis
of this molecule is described. During the course of our studies, a Ni-mediated C
N bond formation was invented, which enabled the rapid construction of the highly
substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich
heterocycle was accomplished in only eight steps starting from readily available
materials.
PMID- 25848823
TI - N-Heterocyclic Carbene-Catalyzed Ring Opening Polymerization of epsilon
Caprolactone with and without Alcohol Initiators: Insights from Theory and
Experiment.
AB - Computational investigations with density functional theory (DFT) have been
performed on the N-heterocyclic carbene (NHC) catalyzed ring-opening
polymerization of epsilon-caprolactone in the presence and in the absence of a
methanol initiator. Much like the zwitterionic ring opening (ZROP) of delta
valerolactone which was previously reported, calculations predict that the
mechanism of the ZROP of caprolactone that occurs without an alcohol present
involves a high-barrier step involving ring opening of the zwitterionic
tetrahedral intermediate formed after the initial nucleophilic attack of NHC on
caprolactone. However, the operative mechanism by which caprolactone is
polymerized in the presence of an alcohol initiator does not involve the
analogous mechanism involving initial nucleophilic attack by the organocatalytic
NHC. Instead, the NHC activates the alcohol through hydrogen bonding and promotes
nucleophilic attack and the subsequent ring-opening steps that occur during
polymerization. The largest free energy barrier for the hydrogen-bonding
mechanism in alcohol involves nucleophilic attack, while that for both ZROP
processes involves ring opening of the initially formed zwitterionic tetrahedral
intermediate. The DFT calculations predict that the rate of polymerization in the
presence of alcohol is faster than the reaction performed without an alcohol
initiator; this prediction has been validated by experimental kinetic studies.
PMID- 25848822
TI - A "Smart" 128Xe NMR Biosensor for pH-Dependent Cell Labeling.
AB - Here we present a "smart" xenon-129 NMR biosensor that undergoes a peptide
conformational change and labels cells in acidic environments. To a cryptophane
host molecule with high Xe affinity, we conjugated a 30mer EALA-repeat peptide
that is alpha-helical at pH 5.5 and disordered at pH 7.5. The (129)Xe NMR
chemical shift at room temperature was strongly pH-dependent (Deltadelta = 3.4
ppm): delta = 64.2 ppm at pH 7.5 vs delta = 67.6 ppm at pH 5.5, where
Trp(peptide)-cryptophane interactions were evidenced by Trp fluorescence
quenching. Using hyper-CEST NMR, we probed peptidocryptophane detection limits at
low-picomolar (10(-11) M) concentration, which compares favorably to other NMR pH
reporters at 10(-2)-10(-3) M. Finally, in biosensor-HeLa cell solutions, peptide
cell membrane insertion at pH 5.5 generated a 13.4 ppm downfield cryptophane
(129)Xe NMR chemical shift relative to pH 7.5 studies. This highlights new uses
for (129)Xe as an ultrasensitive probe of peptide structure and function, along
with potential applications for pH-dependent cell labeling in cancer diagnosis
and treatment.
PMID- 25848825
TI - Emergent and after hours calls in skilled care facilities.
PMID- 25848824
TI - Fracture prevention in COPD patients; a clinical 5-step approach.
AB - Although osteoporosis and its related fractures are common in patients with COPD,
patients at high risk of fracture are poorly identified, and consequently,
undertreated. Since there are no fracture prevention guidelines available that
focus on COPD patients, we developed a clinical approach to improve the
identification and treatment of COPD patients at high risk of fracture. We
organised a round-table discussion with 8 clinical experts in the field of COPD
and fracture prevention in the Netherlands in December 2013. The clinical experts
presented a review of the literature on COPD, osteoporosis and fracture
prevention. Based on the Dutch fracture prevention guideline, they developed a 5
step clinical approach for fracture prevention in COPD. Thereby, they took into
account both classical risk factors for fracture (low body mass index, older age,
personal and family history of fracture, immobility, smoking, alcohol intake, use
of glucocorticoids and increased fall risk) and COPD-specific risk factors for
fracture (severe airflow obstruction, pulmonary exacerbations and oxygen
therapy). Severe COPD (defined as postbronchodilator FEV1 < 50% predicted) was
added as COPD-specific risk factor to the list of classical risk factors for
fracture. The 5-step clinical approach starts with case finding using clinical
risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and
imaging of the spine), differential diagnosis, treatment and follow-up. This
systematic clinical approach, which is evidence-based and easy-to-use in daily
practice by pulmonologists, should contribute to optimise fracture prevention in
COPD patients at high risk of fracture.
PMID- 25848826
TI - Update on managing generalized anxiety disorder in older adults.
AB - With the recent updates to the Diagnostic and Statistical Manual of Mental
Disorders (5th edition; DSM-5), there are many questions on how to care for older
adults with generalized anxiety disorder (GAD) and other psychiatric conditions.
The current article reviews the new changes to the DSM-5 for diagnosis of GAD,
discusses new anxiety assessment scales that are validated in older adults,
evaluates pharmacological agents that have been studied in older adults for GAD
treatment, and provides monitoring recommendations to help those who provide care
to older adults experiencing GAD.
PMID- 25848827
TI - Barriers to better care.
PMID- 25848829
TI - De novo transcriptome sequencing to identify the sex-determination genes in
Hyriopsis schlegelii.
AB - This study presents the first analysis of expressed transcripts in the spermary
and ovary of Hyriopsis schlegelii (H. schlegelii). A total of 132,055 unigenes
were obtained and 31,781 of these genes were annotated. In addition, 19,511
upregulated and 25,911 downregulated unigenes were identified in the spermary.
Ten sex-determination genes were selected and further analyzed by real-time PCR.
In addition, mammalian genes reported to govern sex-determination pathways,
including Sry, Dmrt1, Dmrt2, Sox9, GATA4, and WT1 in males and Wnt4, Rspo1,
Foxl2, and beta-catenin in females, were also identified in H. schlegelii. These
results suggest that H. schlegelii and mammals use similar gene regulatory
mechanisms to control sex determination. Moreover, genes associated with dosage
compensation mechanisms, such as Msl1, Msl2, and Msl3, and hermaphrodite
phenotypes, such as Tra-1, Tra-2alpha, Tra-2beta, Fem1A, Fem1B, and Fem1C, were
also identified in H. schlegelii. The identification of these genes indicates
that diverse regulatory mechanisms regulate sexual polymorphism in H. schlegelii.
PMID- 25848828
TI - Antibody-based screening of cell wall matrix glycans in ferns reveals taxon,
tissue and cell-type specific distribution patterns.
AB - BACKGROUND: While it is kno3wn that complex tissues with specialized functions
emerged during land plant evolution, it is not clear how cell wall polymers and
their structural variants are associated with specific tissues or cell types.
Moreover, due to the economic importance of many flowering plants, ferns have
been largely neglected in cell wall comparative studies. RESULTS: To explore fern
cell wall diversity sets of monoclonal antibodies directed to matrix glycans of
angiosperm cell walls have been used in glycan microarray and in situ analyses
with 76 fern species and four species of lycophytes. All major matrix glycans
were present as indicated by epitope detection with some variations in abundance.
Pectic HG epitopes were of low abundance in lycophytes and the CCRC-M1
fucosylated xyloglucan epitope was largely absent from the Aspleniaceae. The LM15
XXXG epitope was detected widely across the ferns and specifically associated
with phloem cell walls and similarly the LM11 xylan epitope was associated with
xylem cell walls. The LM5 galactan and LM6 arabinan epitopes, linked to pectic
supramolecules in angiosperms, were associated with vascular structures with only
limited detection in ground tissues. Mannan epitopes were found to be associated
with the development of mechanical tissues. We provided the first evidence for
the presence of MLG in leptosporangiate ferns. CONCLUSIONS: The data sets
indicate that cell wall diversity in land plants is multifaceted and that matrix
glycan epitopes display complex spatio-temporal and phylogenetic distribution
patterns that are likely to relate to the evolution of land plant body plans.
PMID- 25848830
TI - Single-Crystalline Aluminum Nanostructures on a Semiconducting GaAs Substrate for
Ultraviolet to Near-Infrared Plasmonics.
AB - Aluminum, as a metallic material for plasmonics, is of great interest because it
extends the applications of surface plasmon resonance into the ultraviolet (UV)
region and is superior to noble metals in natural abundance, cost, and
compatibility with modern semiconductor fabrication processes. Ultrasmooth single
crystalline metallic films are beneficial for the fabrication of high-definition
plasmonic nanostructures, especially complex integrated nanocircuits. The absence
of surface corrugation and crystal boundaries also guarantees superior optical
properties and applications in nanolasers. Here, we present UV to near-infrared
plasmonic resonance of single-crystalline aluminum nanoslits and nanoholes. The
high-definition nanostructures are fabricated with focused ion-beam milling into
an ultrasmooth single-crystalline aluminum film grown on a semiconducting GaAs
substrate with a molecular beam epitaxy method. The single-crystalline aluminum
film shows improved reflectivity and reduced two-photon photoluminescence (TPPL)
due to the ultrasmooth surface. Both linear scattering and nonlinear TPPL are
studied in detail. The nanoslit arrays show clear Fano-like resonance, and the
nanoholes are found to support both photonic modes and localized surface plasmon
resonance. We also found that TPPL generation is more efficient when the
excitation polarization is parallel rather than perpendicular to the edge of the
aluminum film. Such a counterintuitive phenomenon is attributed to the high
refractive index of the GaAs substrate. We show that the polarization of TPPL
from aluminum preserves the excitation polarization and is independent of the
crystal orientation of the film or substrate. Our study gains insight into the
optical property of aluminum nanostructures on a high-index semiconducting GaAs
substrate and illustrates a practical route to implement plasmonic devices onto
semiconductors for future hybrid nanodevices.
PMID- 25848831
TI - A single nucleotide polymorphism in the MTOR gene is associated with recurrent
spontaneous abortion in the Chinese female population.
AB - Recurrent spontaneous abortion (RSA) is a multi-factor disease. The mammalian
target of the the rapamycin (MTOR) gene has been reported to be involved in mouse
embryo development and regulates the proliferation of embryonic stem cells. Our
study explored the relationship between the single nucleotide polymorphism (SNP)
rs17027478 in the promoter region of MTOR gene and the development of RSA. A
total of 306 patients with RSA and 127 healthy females as the controls were
recruited in the case-control study. The predesigned TaqMan SNP Genotyping Assay
was adopted to analyze the association between rs17027478 and the development of
RSA. Quantitative real-time reverse transcription polymerase chain reaction and
luciferase reporter assays were conducted to analyze the function of the variant.
It was found that a significant association exists between the variant and the
risk of RSA among the patients who experienced no less than three spontaneous
abortions (p = 0.043). However, the significant difference disappeared among the
total samples (p = 0.524). Furthermore, we observed lower MTOR mRNA levels in the
blood of RSA patients compared with healthy females (p = 0.020). The luciferase
reporter assay showed that the rs17027478A allele significantly reduced the
luciferase activity (p = 0.029). The results demonstrated that the variant
rs17027478 in the promoter region of MTOR might be a good candidate responsible
for the pathogenesis of RSA. Abbreviations RSA recurrent spontaneous abortion
MTOR mammalian target of rapamycin SNP single nucleotide polymorphism qRT-PCR
quantitative real-time polymerase chain reaction URSA unexplained recurrent
spontaneous abortion mTORC1 mTOR complex 1 ESC embryonic stem cells HKE-293 human
embryonic kidney 293 cells HWE Hardy-Weinberg equilibrium ANOVA one-way analysis
of variance.
PMID- 25848833
TI - Polylactide/Poly(omega-hydroxytetradecanoic acid) Reactive Blending: A Green
Renewable Approach to Improving Polylactide Properties.
AB - A green manufacturing technique, reactive extrusion (REx), was employed to
improve the mechanical properties of polylactide (PLA). To achieve this goal, a
fully biosourced PLA based polymer blend was conceived by incorporating small
quantities of poly(omega-hydroxytetradecanoic acid) (PC14). PLA/PC14 blends were
compatibilized by transesterification reactions promoted by 200 ppm titanium
tetrabutoxide (Ti(OBu)4) during REx. REx for 15 min at 150 rpm and 200 degrees C
resulted in enhanced blend mechanical properties while minimizing losses in PLA
molecular weight. SEM analysis of the resulting compatibilized phase-separated
blends showed good adhesion between dispersed PC14 phases within the continuous
PLA phase. Direct evidence for in situ synthesis of PLA-b-PC14 copolymers was
obtained by HMBC and HSQC NMR experiments. The size of the dispersed phase was
tuned by the screw speed to "tailor" the blend morphology. In the presence of 200
ppm Ti(OBu)4, inclusion of only 5% PC14 increased the elongation at break of PLA
from 3 to 140% with only a slight decrease in the tensile modulus (3200 to 2900
MPa). Furthermore, PLA's impact strength was increased by 2.4* that of neat PLA
for 20% PC14 blends prepared by REx. Blends of PLA and PC14 are expected to
expand the potential uses of PLA-based materials.
PMID- 25848832
TI - Heroin activates ATF3 and CytC via c-Jun N-terminal kinase pathways to mediate
neuronal apoptosis.
AB - BACKGROUND Drug abuse and addiction has become a major public health problem that
impacts all societies. The use of heroin may cause spongiform leukoencephalopathy
(SLE). MATERIAL AND METHODS Cerebellar granule cells were derived from 7-day-old
Sprague-Dawley rat pups. Neurons were dissociated from freshly dissected
cerebella by mechanical disruption in the presence of 0.125% trypsin and DNaseI
and then seeded at a density of 4*10^6 cells/ml in Dulbecco's modified Eagle's
medium/nutrient mixture F-12 ham's containing 10% fetal bovine serum and Arc
C(sigma) at concentrations to inhibit glial cell growth inoculated into 6-well
plates and a small dish. RESULTS We found that heroin induces the apoptosis of
primary cultured cerebellar granule cells (CGCS) and that the c-Jun N-terminal
kinase (JNK) pathway was activated under heroin treatment and stimulated obvious
increases in the levels of C-jun, Cytc, and ATF3mRNA. CYTC and ATF3 were
identified as candidate targets of the JNK/c-Jun pathway in this process because
the specificity inhibitors SP600125 of JNK/C-jun pathways reduced the levels of C
jun, Cytc, and ATF3mRNA. The results suggested that SP600125 of JNK/C-jun can
inhibit heroin-induced apoptosis of neurons. CONCLUSIONS The present study
analyzes our understanding of the critical role of the JNK pathway in the process
of neuronal apoptosis induced by heroin, and suggests a new and effective
strategy to treat SLE.
PMID- 25848834
TI - Synthesis of Strong Light Scattering Absorber of TiO2-CMK-3/Ag for Photocatalytic
Water Splitting under Visible Light Irradiation.
AB - The enhanced water splitting photocurrent has been observed through plasmonic
mesoporous composite electrode TiO2-CMK-3/Ag under visible light irradiation.
Strong light absorption achieved from the integrations of ordered mesoporous
carbon (CMK-3) and silver plasmonic nanoparticles (NPs) layer in the TiO2, which
significantly increased the effective optical depth of TiO2-CMK-3/Ag
photoelectrode. The carbon-based CMK-3 also increased the surface wetting
behavior and conductivity of the photoelectrodes, which resulted in a higher ion
exchange rate and faster electron transport. The synthesis of high crystalline
TiO2-CMK-3/Ag composite photocatalyst was verified by X-ray diffraction (XRD) and
scanning electron microscopy (SEM). Pronounced enhancement of light absorption of
TiO2-CMK-3/Ag photoelectrode was confirmed by UV/vis spectrophotometers. Two
orders of magnitude of the enhanced water splitting photocurrent were obtained in
the TiO2-CMK-3/Ag composite photoelectrode with respect to TiO2 only. Finally,
spatially resolved mapping photocurrents were also demonstrated in this study.
PMID- 25848835
TI - Potential ecological roles of flavonoids from Stellera chamaejasme.
AB - Stellera chamaejasme L. (Thymelaeaceae), a perennial weed, distributes widely in
the grasslands of Russia, Mongolia and China. The plant synthesizes various
secondary metabolites including a group of flavonoids. To our knowledge,
flavonoids play important roles in the interactions between plants and the
environment. So, what are the benefits to S. chamaejasme from producing these
flavonoids? Here, we discuss the potential ecological role of flavonoids from S.
chamaejasme in protecting the plant from insects and other herbivores, as well as
pathogens and competing plant species, and new data are provided on the
phytotoxicity of flavonoids from S. chamaejasme toward Poa annua L.
PMID- 25848836
TI - Feasibility of Using Phytoextraction to Remediate a Compost-Based Soil
Contaminated with Cadmium.
AB - Greenhouse and in-situ field experiments were used to determine the potential for
phytoextraction to remediate soil contaminated with Cd from municipal solid waste
(MSW) and sewage sludge (SS) compost application at a Peterborough (Canada) site.
For the greenhouse experiment, one native (Chenopodium album) and three
naturalized (Poa compressa, Brassica juncea, Helianthus annuus) plant species
were planted in soil containing no detectable Cd (<1.0 MUg.g(-1)), and soil from
the site containing low (5.0 +/- 0.3 MUg.g(-1) Cd), and high (16.5 +/- 1.2 MUg?g(
1) Cd) Cd concentrations. Plant uptake was low (root BAFs <=0.5) for all species
except P. compressa in the low Cd treatment (BAF 1.0). Only B. juncea accumulated
Cd in its shoots, though uptake was low (BAF <=0.3). For the field experiment, B.
juncea was planted in-situ in areas of low and high Cd concentrations. Brassica
juncea Cd uptake was low (root and shoot BAFs <0.2) in both treatments.
Sequential extraction analysis indicated that Cd is retained primarily by low
bioavailability soil fractions, and phytoextraction is therefore not feasible at
this site. Though low Cd bioavailability has negative implications for Cd
phytoextraction from MSW/SS compost-based soils, it may limit receptor exposure
to Cd sufficiently to eliminate the potential for risk at this site.
PMID- 25848838
TI - Perceptions of a good death among German medical students.
AB - The purpose of our study was to examine the perceptions of a good death among
medical students, who are future care providers. The authors identified 9 domains
that contribute to a good death according to first- and fifth-year medical
students (N=432). From their perspective, being free from pain and physical
distress is only 1 important component of a good death, and other elements such
as psychosocial issues should also be taken into account. A majority of medical
students considers psychosocial well-being as a highly relevant aspect of
patients' conditions. The results of this study could help to develop concepts
for better care and more empathy, which are needed to ensure a good death for all
patients.
PMID- 25848837
TI - Proteomic and metabolomic analyses provide insight into production of volatile
and non-volatile flavor components in mandarin hybrid fruit.
AB - BACKGROUND: Although many of the volatile constituents of flavor and aroma in
citrus have been identified, the knowledge of molecular mechanisms and regulation
of volatile production are very limited. Our aim was to understand mechanisms of
flavor volatile production and regulation in mandarin fruit. RESULT: Fruits of
two mandarin hybrids, Temple and Murcott with contrasting volatile and non-
volatile profiles, were collected at three developmental stages. A combination of
methods, including the isobaric tags for relative and absolute quantification
(iTRAQ), quantitative real-time polymerase chain reaction, gas chromatography,
and high-performance liquid chromatography, was used to identify proteins,
measure gene expression levels, volatiles, sugars, organic acids and carotenoids.
Two thirds of differentially expressed proteins were identified in the pathways
of glycolysis, citric acid cycle, amino acid, sugar and starch metabolism. An
enzyme encoding valencene synthase gene (Cstps1) was more abundant in Temple than
in Murcott. Valencene accounted for 9.4% of total volatile content in Temple,
whereas no valencene was detected in Murcott fruit. Murcott expression of Cstps1
is severely reduced. CONCLUSION: We showed that the diversion of valencene and
other sesquiterpenes into the terpenoid pathway together with high production of
apocarotenoid volatiles might have resulted in the lower concentration of
carotenoids in Temple fruit.
PMID- 25848839
TI - Sarcomere Disruptions of Slow Fiber Resulting From Mountain Ultramarathon.
AB - OBJECTIVE: To investigate changes after a mountain ultramarathon (MUM) in the
serum concentration of fast (FM) and slow (SM) myosin isoforms, which are fiber
type-specific sarcomere proteins. The changes were compared against creatine
kinase (CK), a widely used fiber-sarcolemma-damage biomarker, and cardiac
troponin I (cTnI), a widely used cardiac biomarker. METHODS: Observational
comparison of response in a single group of 8 endurance-trained amateur athletes.
Time-related changes in serum levels of CK, cTnI, SM, and FM from competitors
were analyzed before, 1 h after the MUM, and 24 and 48 h after the start of the
MUM by 1-way ANOVA for repeated measures or Friedman and Wilcoxon tests. Pearson
correlation coefficient was employed to examine associations between variables.
RESULTS: While SM was significantly (P = .009) increased in serum 24 h after the
beginning of the MUM, FM and cTnI did not change significantly. Serum CK activity
peak was observed 1 h after the MUM (P = .002). Moreover, serum peaks of CK and
SM were highly correlated (r = .884, P = .004). CONCLUSIONS: Since there is
evidence of muscle damage after prolonged mountain running, the increase in SM
serum concentration after a MUM could be indirect evidence of slow- (type I)
fiber-specific sarcomere disruptions.
PMID- 25848840
TI - Increased Serum Chemerin Levels in Diabetic Retinopathy of Type 2 Diabetic
Patients.
AB - PURPOSE: To compare serum levels of chemerin in type 2 diabetes mellitus (T2DM)
with or without retinopathy, and to investigate the relationship between serum
chemerin levels and diabetes retinopathy. MATERIALS AND METHODS: A total of 60
T2DM patients and 20 healthy subjects (control group) were enrolled in this
study. Of the T2DM patients, 15 had proliferative diabetic retinopathy (PDR
group), 20 had non-proliferative retinopathy (NPDR group) and 25 had no
retinopathy (T2DM group). Their serum samples were collected for testing the
levels of chemerin, vascular endothelial growth factor (VEGF), C-reactive protein
(CRP) and so on. The values were analyzed to compare the differences among the
groups. Simple linear regression analysis and multiple stepwise linear regression
analysis were used to determine the correlations between variables and chemerin.
Trend chi-square was used to determine the correlations between chemerin and the
severity of diabetic retinopathy (DR). RESULTS: Chemerin levels in group PDR,
NPDR and no DR were 147.56 +/- 35.98 MUg/l, 128.09 +/- 16.33 MUg/l and 113.19 +/-
19.89 MUg/l, with the significant difference across the three groups (p < 0.05).
But there was no difference between control group (109.55 +/- 20.98 MUg/l) and
T2DM group. Simple linear regression show that serum chemerin was correlated with
duration of diabetes, body mass index (BMI), serum triglycerides, total
cholesterol, CRP and VEGF, and not correlated with age, systolic and diastolic
blood pressure in T2DM patients. Stepwise regression analysis showed that BMI,
CRP and VEGF were significantly associated with serum chemerin (p = 0.006, p =
0.011 and p = 0.036, respectively). In addition, the more severity of DR as the
chemerin levels increased (chi(2) = 16.07, p < 0.001). CONCLUSIONS: Serum levels
of chemerin were significantly increased in the NPDR and PDR group. Elevated
serum level of chemerin and its positive correlation with BMI, CRP and VEGF
suggested that chemerin was associated with obesity, inflammation and
neovascularization and might be involved in the development of DR.
PMID- 25848841
TI - Can nurses exclude middle-ear effusion without otoscopy in young asymptomatic
children in primary care?
AB - OBJECTIVE: Scandinavian guidelines recommend controlling middle-ear effusion
(MEE) after acute otitis media. The study aim was to determine whether nurses
without otoscopic experience can reliably exclude MEE with tympanometry or
spectral gradient acoustic reflectometry (SG-AR) at asymptomatic visits. DESIGN:
Three nurses were taught to perform examinations with tympanometry and SG-AR.
Pneumatic otoscopy by the study physician served as the diagnostic standard.
SETTING: Study clinic at primary health care level. PATIENTS: A total of 156
children aged 6-35 months. MAIN OUTCOME MEASURES: Predictive values (with 95%
confidence interval) for tympanometry and SG-AR, and the clinical usefulness,
i.e. the proportion of visits where nurses obtained the exclusive test result
from both ears of the child. RESULTS: At 196 visits, the negative predictive
value of type A and C1 tympanograms (tympanometric peak pressure > -200 daPa) was
95% (91-97%). Based on type A and C1 tympanograms, the nurse could exclude MEE at
81/196 (41%) of visits. The negative predictive value of SG-AR level 1 result was
86% (79-91%). Based on SG-AR level 1 results, the nurse could exclude MEE at
29/196 (15%) of visits. CONCLUSION: Tympanograms with tympanometric peak pressure
> -200 daPa (types A and C1) obtained by nurses are reliable test results in
excluding MEE. However, these test results were obtained at less than half of the
asymptomatic visits and, thus, the usefulness of excluding MEE by nurses depends
on the clinical setting.
PMID- 25848842
TI - Overexpression of a truncated CTF7 construct leads to pleiotropic defects in
reproduction and vegetative growth in Arabidopsis.
AB - BACKGROUND: Eco1/Ctf7 is essential for the establishment of sister chromatid
cohesion during S phase of the cell cycle. Inactivation of Ctf7/Eco1 leads to a
lethal phenotype in most organisms. Altering Eco1/Ctf7 levels or point mutations
in the gene can lead to alterations in nuclear division as well as a wide range
of developmental defects. Inactivation of Arabidopsis CTF7 (AtCTF7) results in
severe defects in reproduction and vegetative growth. RESULTS: To further
investigate the function(s) of AtCTF7, a tagged version of AtCTF7 and several
AtCTF7 deletion constructs were created and transformed into wild type or ctf7 +/
plants. Transgenic plants expressing 35S:NTAP:AtCTF7?299-345 (AtCTF7?B)
displayed a wide range of phenotypic alterations in reproduction and vegetative
growth. Male meiocytes exhibited chromosome fragmentation and uneven chromosome
segregation. Mutant ovules contained abnormal megasporocyte-like cells during pre
meiosis, megaspores experienced elongated meiosis and megagametogenesis, and
defective megaspores/embryo sacs were produced at various stages. The transgenic
plants also exhibited a broad range of vegetative defects, including meristem
disruption and dwarfism that were inherited in a non-Mendelian fashion.
Transcripts for epigenetically regulated transposable elements (TEs) were
elevated in transgenic plants. Transgenic plants expressing 35S:AtCTF7?B
displayed similar vegetative defects, suggesting the defects in 35S:NTAP:AtCTF7?B
plants are caused by high-level expression of AtCTF7?B. CONCLUSIONS: High level
expression of AtCTF7?B disrupts megasporogenesis, megagametogenesis and male
meiosis, as well as causing a broad range of vegetative defects, including
dwarfism that are inherited in a non-Mendelian fashion.
PMID- 25848843
TI - Local origin of mesenchymal cells in a murine orthotopic lung transplantation
model of bronchiolitis obliterans.
AB - Bronchiolitis obliterans is the leading cause of chronic graft failure and long
term mortality in lung transplant recipients. Here, we used a novel murine model
to characterize allograft fibrogenesis within a whole-lung microenvironment.
Unilateral left lung transplantation was performed in mice across varying degrees
of major histocompatibility complex mismatch combinations. B6D2F1/J (a cross
between C57BL/6J and DBA/2J) (Haplotype H2b/d) lungs transplanted into DBA/2J
(H2d) recipients were identified to show histopathology for bronchiolitis
obliterans in all allogeneic grafts. Time course analysis showed an evolution
from immune cell infiltration of the bronchioles and vessels at day 14,
consistent with acute rejection and lymphocytic bronchitis, to subepithelial and
intraluminal fibrotic lesions of bronchiolitis obliterans by day 28. Allografts
at day 28 showed a significantly higher hydroxyproline content than the isografts
(33.21 +/- 1.89 versus 22.36 +/- 2.33 MUg/mL). At day 40 the hydroxyproline
content had increased further (48.91 +/- 7.09 MUg/mL). Flow cytometric analysis
was used to investigate the origin of mesenchymal cells in fibrotic allografts.
Collagen I-positive cells (89.43% +/- 6.53%) in day 28 allografts were H2Db
positive, showing their donor origin. This novel murine model shows consistent
and reproducible allograft fibrogenesis in the context of single-lung
transplantation and represents a major step forward in investigating mechanisms
of chronic graft failure.
PMID- 25848844
TI - Peripheral neuromodulation for the treatment of refractory trigeminal neuralgia.
AB - Trigeminal neuralgia is a type of orofacial pain that is diagnosed in 150,000
individuals each year, with an incidence of 12.6 per 100,000 person-years and a
prevalence of 155 cases per 1,000,000 in the United States. Trigeminal neuralgia
pain is characterized by sudden, severe, brief, stabbing or lancinating,
recurrent episodes of pain in the distribution of one or more branches of the
trigeminal nerve, which can cause significant suffering for the affected patient
population. In many patients, a combination of medication and interventional
treatments can be therapeutic, but is not always successful. Peripheral nerve
stimulation has gained popularity as a simple and effective neuromodulation
technique for the treatment of many pain conditions, including chronic headache
disorders. Specifically in trigeminal neuralgia, neurostimulation of the
supraorbital and infraorbital nerves may serve to provide relief of neuropathic
pain by targeting the distal nerves that supply sensation to the areas of the
face where the pain attacks occur, producing a field of paresthesia within the
peripheral distribution of pain through the creation of an electric field in the
vicinity of the leads. The purpose of the present case report is to introduce a
new, less-invasive interventional technique, and to describe the authors' first
experience with supraorbital and infraorbital neurostimulation therapy for the
treatment of trigeminal neuralgia in a patient who had failed previous
conservative management.
PMID- 25848845
TI - Development and validation of the French-Canadian Chronic Pain Self-efficacy
Scale.
AB - BACKGROUND: Perceived self-efficacy is a non-negligible outcome when measuring
the impact of self-management interventions for chronic pain patients. However,
no validated, chronic pain-specific self-efficacy scales exist for studies
conducted with French-speaking populations. OBJECTIVES: To establish the validity
of the use of the French-Canadian Chronic Pain Self-efficacy Scale (FC-CPSES)
among chronic pain patients. METHODS: The Chronic Disease Self-Efficacy Scale is
a validated 33-item self-administered questionnaire that measures perceived self
efficacy to perform self-management behaviours, manage chronic disease in general
and achieve outcomes (a six-item version is also available). This scale was
adapted to the context of chronic pain patients following cross-cultural
adaptation guidelines. The FC-CPSES was administered to 109 fibromyalgia and 34
chronic low back pain patients (n=143) who participated in an evidence-based self
management intervention (the PASSAGE program) offered in 10 health care centres
across the province of Quebec. Cronbach's alpha coefficients (alpha) were
calculated to determine the internal consistency of the 33- and six-item versions
of the FC-CPSES. With regard to convergent construct validity, the association
between the FC-CPSES baseline scores and related clinical outcomes was examined.
With regard to the scale's sensitivity to change, pre- and postintervention FC
CPSES scores were compared. RESULTS: Internal consistency was high for both
versions of the FC-CPSES (alpha=0.86 to alpha=0.96). Higher self-efficacy was
significantly associated with higher mental health-related quality of life and
lower pain intensity and catastrophizing (P<0.05), supporting convergent validity
of the scale. There was a statistically significant increase in FC-CPSES scores
between pre- and postintervention measures for both versions of the FC-CPSES
(P<0.003), which supports their sensitivity to clinical change during an
intervention. CONCLUSIONS: These data suggest that both versions of the FC-CPSES
are reliable and valid for the measurement of pain management self-efficacy among
chronic pain patients.
PMID- 25848846
TI - Turn-amplitude analysis as a diagnostic test for myofascial syndrome in patients
with chronic pelvic pain.
AB - BACKGROUND: Myofascial pain syndrome of the pelvic floor (MPSPF) is a common
disease in the context of chronic pelvic pain (CPP); however, there is currently
no gold-standard test to diagnose it. OBJECTIVE: To validate the turns-amplitude
analysis (TAA) as a diagnostic test for MPSPF in patients with CPP. METHODS: A
case-control study was performed, and patients were consecutively sampled within
a specified period of time. A total of 128 patients were included: 64 patients
with CPP (32 men and 32 women) and 64 control patients (32 men and 32 women). The
same operator conducted all tests. Electromyography of the TAA is based on the
collection of motor unit potentials that measure the number of changes in the
signal and the mean amplitude of the changes. The electromyogram transfers the
data to a graphical point cloud, which enables the patient's results to be
compared with the results of the healthy subjects. RESULTS: In patients and
control subjects, the sensitivity and specificity of the proposed diagnostic test
showed a marked clinical significance: the sensitivity was 83%, and the
specificity was 100%. A positive predictive value of 1 (95% CI 1 to 1) and a
negative predictive value of 0.85 (95% CI 0.77 to 0.93) were observed.
CONCLUSION: TAA is a reliable diagnostic test to detect MPSPF. Further studies
are needed to reproduce these results.
PMID- 25848847
TI - [Nursing activities in family medicine groups for patients with chronic pain].
AB - INTRODUCTION: Thousands of people treated in primary care are currently
experiencing chronic pain (CP), for which management is often inadequate. In
Quebec, nurses in family medicine groups (FMGs) play a key role in the management
of chronic health problems. OBJECTIVE: The present study aimed to describe the
activities performed by FMG nurses in relation to CP management and to describe
barriers to those activities. METHOD: A descriptive correlational cross-sectional
postal survey was used. The accessible population includes FMG nurses on the
Ordre des infirmieres et infirmiers du Quebec list. All nurses on the list who
provided consent to be contacted at home for research purposes were contacted. A
self-administered postal questionnaire (Pain Management Activities Questionnaire)
was completed by 53 FMG nurses. RESULTS: Three activities most often performed by
nurses were to establish a therapeutic relationship with the client; discuss the
effectiveness of therapeutic measures with the physician; and conduct
personalized teaching for the patient. The average number of individuals seen by
interviewed nurses that they believe suffer from CP was 2.68 per week. The lack
of knowledge of possible interventions in pain management (71.7%) and the
nonavailability of information on pain management (52.8%) are the main barriers
perceived by FMG nurses. CONCLUSION: FMG nurses are currently performing few
activities in CP management. The nonrecognition of CP may explain this situation.
PMID- 25848848
TI - Comparison of four different pain relief methods during hysterosalpingography: a
randomized controlled study.
AB - BACKGROUND: Hysterosalpingography (HSG) is the most commonly used method for
evaluating the anatomy and patency of the uterine cavity and fallopian tubes, and
is an important tool in the evaluation of infertility. The most frequent side
effect is the pain associated with the procedure. OBJECTIVES: To evaluate four
analgesic methods to determine the most useful method for reducing discomfort
associated with HSG. METHODS: In the present prospective study, 75 patients
undergoing HSG for evaluation of infertility were randomly assigned to four
groups: 550 mg of a nonsteroidal anti-inflammatory drug (NSAID) (group 1); 550 mg
NSAID + paracervical block (group 2); 550 mg NSAID + paracervical analgesic cream
(group 3); or 550 mg NSAID + intrauterine analgesic instillation (group 4). A
visual analogue scale was used to assess the pain perception at five predefined
steps. RESULTS: Instillation of the liquids used for HSG was found to be the most
painful step of HSG, and this step was where the only significant difference
among groups was observed. When comparing visual analogue scale scores, group 2
and group 3 reported significantly less pain than the other groups. Group 1
reported significantly higher mean (+/- SD) scores (7.2 +/- 1.6) compared with
groups 2 and 3 (4.7 +/- 2.5 and 3.8 +/- 2.4, respectively) (P<0.001). In
addition, group 2 reported significantly less pain than group 4 (4. 7 +/- 2.5
versus 6.7 +/- 1.8, respectively) (P<0.02). CONCLUSIONS: For effective pain
relief during HSG, in addition to 550 mg NSAID, local application of lidocaine
cream to the posterior fornix of the cervix uteri and paracervical lidocaine
injection into the cervix uteri appear to be the most effective methods.
PMID- 25848849
TI - The Physcomitrella patens unique alpha-dioxygenase participates in both
developmental processes and defense responses.
AB - BACKGROUND: Plant alpha-dioxygenases catalyze the incorporation of molecular
oxygen into polyunsaturated fatty acids leading to the formation of oxylipins. In
flowering plants, two main groups of alpha-DOXs have been described. While the
alpha-DOX1 isoforms are mainly involved in defense responses against microbial
infection and herbivores, the alpha-DOX2 isoforms are mostly related to
development. To gain insight into the roles played by these enzymes during land
plant evolution, we performed biochemical, genetic and molecular analyses to
examine the function of the single copy moss Physcomitrella patens alpha-DOX
(Ppalpha-DOX) in development and defense against pathogens. RESULTS: Recombinant
Ppalpha-DOX protein catalyzed the conversion of fatty acids into 2-hydroperoxy
derivatives with a substrate preference for alpha-linolenic, linoleic and
palmitic acids. Ppalpha-DOX is expressed during development in tips of young
protonemal filaments with maximum expression levels in mitotically active
undifferentiated apical cells. In leafy gametophores, Ppalpha-DOX is expressed in
auxin producing tissues, including rhizoid and axillary hairs. Ppalpha-DOX
transcript levels and Ppalpha-DOX activity increased in moss tissues infected
with Botrytis cinerea or treated with Pectobacterium carotovorum elicitors. In B.
cinerea infected leaves, Ppalpha-DOX-GUS proteins accumulated in cells
surrounding infected cells, suggesting a protective mechanism. Targeted
disruption of Ppalpha-DOX did not cause a visible developmental alteration and
did not compromise the defense response. However, overexpressing Ppalpha-DOX, or
incubating wild-type tissues with Ppalpha-DOX-derived oxylipins, principally the
aldehyde heptadecatrienal, resulted in smaller moss colonies with less protonemal
tissues, due to a reduction of caulonemal filament growth and a reduction of
chloronemal cell size compared with normal tissues. In addition, Ppalpha-DOX
overexpression and treatments with Ppalpha-DOX-derived oxylipins reduced cellular
damage caused by elicitors of P. carotovorum. CONCLUSIONS: Our study shows that
the unique alpha-DOX of the primitive land plant P. patens, although apparently
not crucial, participates both in development and in the defense response against
pathogens, suggesting that alpha-DOXs from flowering plants could have originated
by duplication and successive functional diversification after the divergence
from bryophytes.
PMID- 25848851
TI - Water-soluble phosphorescent ruthenium complex with a fluorescent coumarin unit
for ratiometric sensing of oxygen levels in living cells.
AB - Dual emission was applied to a molecular probe for the ratiometric sensing of
oxygen concentration in a living system. We prepared ruthenium complexes
possessing a coumarin unit (Ru-Cou), in which the (3)MLCT phosphorescence of the
ruthenium complex was efficiently quenched by molecular oxygen, whereas the
coumarin unit emitted constant fluorescence independent of the oxygen
concentration. The oxygen status could be determined precisely from the ratio of
phosphorescence to fluorescence. We achieved the molecular imaging of cellular
oxygen levels using Ru-Cou possessing an alkyl chain, which provided appropriate
lipophilicity to increase cellular uptake.
PMID- 25848852
TI - Advanced DNA- and Protein-based Methods for the Detection and Investigation of
Food Allergens.
AB - Currently, food allergies are an important health concern worldwide. The presence
of undeclared allergenic ingredients or the presence of traces of allergens due
to contamination during food processing poses a great health risk to sensitized
individuals. Therefore, reliable analytical methods are required to detect and
identify allergenic ingredients in food products. The present review addresses
the recent developments regarding the application of DNA- and protein-based
methods for the detection of allergenic ingredients in foods. The fitness-for
purpose of reviewed methodology will be discussed, and future trends will be
highlighted. Special attention will be given to the evaluation of the potential
of newly developed and promising technologies that can improve the detection and
identification of allergenic ingredients in foods, such as the use of biosensors
and/or nanomaterials to improve detection limits, specificity, ease of use, or to
reduce the time of analysis. Such rapid food allergen test methods are required
to facilitate the reliable detection of allergenic ingredients by control
laboratories, to give the food industry the means to easily determine whether its
product has been subjected to cross-contamination and, simultaneously, to
identify how and when this cross-contamination occurred.
PMID- 25848850
TI - Potentiating the cellular targeting and anti-tumor activity of Dp44mT via binding
to human serum albumin: two saturable mechanisms of Dp44mT uptake by cells.
AB - Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) demonstrates potent
anti-cancer activity. We previously demonstrated that 14C-Dp44mT enters and
targets cells through a carrier/receptor-mediated uptake process. Despite
structural similarity, 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT) and
pyridoxal isonicotinoyl hydrazone (PIH) enter cells via passive diffusion.
Considering albumin alters the uptake of many drugs, we examined the effect of
human serum albumin (HSA) on the cellular uptake of Dp44mT, Bp4eT and PIH.
Chelator-HSA binding studies demonstrated the following order of relative
affinity: Bp4eT~PIH>Dp44mT. Interestingly, HSA decreased Bp4eT and PIH uptake,
potentially due to its high affinity for the ligands. In contrast, HSA markedly
stimulated Dp44mT uptake by cells, with two saturable uptake mechanisms
identified. The first mechanism saturated at 5-10 uM (B(max):1.20+/-0.04 * 107
molecules/cell; K(d):33+/-3 uM) and was consistent with a previously identified
Dp44mT receptor/carrier. The second mechanism was of lower affinity, but higher
capacity (B(max):2.90+/-0.12 * 107 molecules/cell; K(d):65+/-6 uM), becoming
saturated at 100 uM and was only evident in the presence of HSA. This second
saturable Dp44mT uptake process was inhibited by excess HSA and had
characteristics suggesting it was mediated by a specific binding site.
Significantly, the HSA-mediated increase in the targeting of Dp44mT to cancer
cells potentiated apoptosis and could be important for enhancing efficacy.
PMID- 25848853
TI - Do routinely measured risk factors for obesity explain the sex gap in its
prevalence? Observations from Saudi Arabia.
AB - BACKGROUND: The prevalence of adult obesity is higher in women than men in most
countries. However, the pathways that link female sex with excess obesity are
still not fully understood. We examine whether socioeconomic and behavioural
factors may mediate the association between sex and obesity in the Saudi Arabian
setting where there is female excess in obesity. METHODS: We performed a
mediation analysis using a cross-sectional, national household survey from Saudi
Arabia with 4758 participants (51% female). A series of multivariable regression
models were fitted to test if socioeconomic position, physical activity,
sedentary behaviour, diet, and smoking mediate the association between sex and
obesity (BMI >=30). The findings were confirmed using causal mediation analysis.
RESULTS: Women in this sample were roughly twice as likely as men to be obese
(crude OR 1.9; 95% CI 1.6-2.3). The odds ratio remained significantly higher for
women compared to men in models testing for mediation (OR range 1.95-2.06). Our
data suggest that indicators of socio-economic position, physical activity,
sedentary behaviour, diet, and smoking do not mediate the sex differences in
obesity. CONCLUSIONS: Our analysis shows that most commonly measured risk factors
for obesity do not explain the sex differences in its prevalence in the Saudi
context. Further research is needed to understand what might explain the female
excess in obesity prevalence. We discuss how data related to the lived experience
of Saudi men and women may tap into underlying mechanisms by which the sex
difference in obesity prevalence are produced.
PMID- 25848854
TI - Integrated pest management of "Golden Delicious" apples.
AB - Monitoring of plant protection product (PPP) residues in "Golden Delicious"
apples was performed in 2011-2013, where 216 active substances were analysed with
three analytical methods. Integrated pest management (IPM) production and
improved IPM production were compared. Results were in favour of improved IPM
production. Some active compounds determined in IPM production (boscalid,
pyraclostrobin, thiacloprid and thiametoxam) were not found in improved IPM
production. Besides that, in 2011 and 2012, captan residues were lower in
improved IPM production. Risk assessment was also performed. Chronic exposure of
consumers was low in general, but showed no major differences for IPM and
improved IPM production for active substances determined in both types of
production. Analytical results were compared with the European Union report of
2010 where 1.3% of apple samples exceeded maximum residue levels (MRLs), while
MRL exceedances were not observed in this survey.
PMID- 25848855
TI - Efficient directional excitation of surface plasmons by a single-element
nanoantenna.
AB - Directional light scattering is important in basic research and real
applications. This area has been successfully downscaled to wavelength and
subwavelength scales with the development of optical antennas, especially single
element nanoantennas. Here, by adding an auxiliary resonant structure to a single
element plasmonic nanoantenna, we show that the highly efficient lowest-order
antenna mode can be effectively transferred into inactive higher-order modes. On
the basis of this mode conversion, scattered optical fields can be well
manipulated by utilizing the interference between different antenna modes. Both
broadband directional excitation of surface plasmon polaritons (SPPs) and
inversion of SPP launching direction at different wavelengths are experimentally
demonstrated as typical examples. The proposed strategy based on mode conversion
and mode interference provides new opportunities for the design of nanoscale
optical devices, especially directional nanoantennas.
PMID- 25848856
TI - Effects of spring temperatures on the strength of selection on timing of
reproduction in a long-distance migratory bird.
AB - Climate change has differentially affected the timing of seasonal events for
interacting trophic levels, and this has often led to increased selection on
seasonal timing. Yet, the environmental variables driving this selection have
rarely been identified, limiting our ability to predict future ecological impacts
of climate change. Using a dataset spanning 31 years from a natural population of
pied flycatchers (Ficedula hypoleuca), we show that directional selection on
timing of reproduction intensified in the first two decades (1980-2000) but
weakened during the last decade (2001-2010). Against expectation, this pattern
could not be explained by the temporal variation in the phenological mismatch
with food abundance. We therefore explored an alternative hypothesis that
selection on timing was affected by conditions individuals experience when
arriving in spring at the breeding grounds: arriving early in cold conditions may
reduce survival. First, we show that in female recruits, spring arrival date in
the first breeding year correlates positively with hatch date; hence, early
hatched individuals experience colder conditions at arrival than late-hatched
individuals. Second, we show that when temperatures at arrival in the recruitment
year were high, early-hatched young had a higher recruitment probability than
when temperatures were low. We interpret this as a potential cost of arriving
early in colder years, and climate warming may have reduced this cost. We thus
show that higher temperatures in the arrival year of recruits were associated
with stronger selection for early reproduction in the years these birds were
born. As arrival temperatures in the beginning of the study increased, but
recently declined again, directional selection on timing of reproduction showed a
nonlinear change. We demonstrate that environmental conditions with a lag of up
to two years can alter selection on phenological traits in natural populations,
something that has important implications for our understanding of how climate
can alter patterns of selection in natural populations.
PMID- 25848857
TI - The Significance of Living Together and Importance of Marriage in Same-Sex
Couples.
AB - Because marriage has been denied to same-sex couples, it is likely that the
meaning and significance ascribed to non-marital cohabitation may be unique.
Further, it is unclear whether same-sex couples view marriage as important to
their relationships, and if they do, why. Using qualitative data from 526
individuals in cohabiting same-sex relationships across 47 states, we explored
(1) the meaning and significance of cohabitation and (2) the perceived importance
of legal marriage to the relationship. Participants viewed cohabitation as
significant, most commonly because it indicates long-term commitment, provides
emotional support, makes the couple a family, and allows them to share life
together. Marriage was perceived as important to a majority (90%), most commonly
because it confers financial and legal benefits, relational legitimacy, and
demonstrates the same commitment as different-sex couples. Overall, findings
highlight the symbolic significance of cohabitation and importance of access to
legal marriage to adults in same-sex relationships.
PMID- 25848858
TI - Health and ecological hazards due to natural radioactivity in soil from mining
areas of Nasarawa State, Nigeria.
AB - Nasarawa State is located in north central Nigeria and it is known as Nigeria's
home of solid minerals. It is endowed with barite, copper, zinc, tantalite and
granite. Continuous releases of mining waste and tailings into the biosphere may
result in a build-up of radionuclides in air, water and soil. This work therefore
aims to measure the activity concentration levels of primordial radionuclides in
the soil/sediment samples collected from selected mines of the mining areas of
Nasarawa State. The paper also assesses the radiological and radio ecological
impacts of mining activities on the residents of mining areas and their
environment. The activity concentrations of primordial radionuclides ((226)Ra,
(232)Th and (40)K) in the surface soils/sediment samples were determined using
sodium iodide-thallium gamma spectroscopy. Seven major mines were considered with
21 samples taken from each of the mines for radiochemistry analysis. The human
health hazard assessment was conducted using regulatory methodologies set by the
United Nations Scientific Committee on the Effects of Atomic Radiation, while the
radio ecological impact assessment was conducted using the ERICA tool v. 1.2. The
result shows that the activity concentrations of (40)K in the water ways of the
Akiri copper and the Azara barite mines are 60 and 67% higher than the world
average value for (40)K, respectively. In all mines, the annual effective dose
rates (mSv y(-1)) were less than unity, and a maximum annual gonadal dose of 0.58
mSv y(-1) is received at the Akiri copper mine, which is almost twice the world
average value for gonadal dose. The external hazard indices for all the mines
were less than unity. Our results also show that mollusc-gastropod, insect
larvae, mollusc-bivalve and zooplankton are the freshwater biotas with the
highest dose rates ranging from 5 to 7 uGy h(-1). These higher dose rates could
be associated with zinc and copper mining at Abuni and Akiri, respectively. The
most exposed terrestrial reference organisms are lichen and bryophytes. In all
cases, the radio ecological risks are not likely to be discernible. This paper
presents a pioneer data for ecological risk from ionizing contaminants due to
mining activity in Nasarawa State, Nigeria. Its methodology could be adopted for
future work on radioecology of mining.
PMID- 25848860
TI - Importance of suppression of Yb(3+) de-excitation to upconversion enhancement in
beta-NaYF4: Yb(3+)/Er(3+)@beta-NaYF4 sandwiched structure nanocrystals.
AB - Nanosized Yb(3+) and Er(3+) co-doped beta-NaYF4 cores coated with multiple beta
NaYF4 shell layers were synthesized by a solvothermal process. X-ray diffraction
and scanning electron microscopy were used to characterize the crystal structure
and morphology of the materials. The visible and near-infrared spectra as well as
the decay curves were also measured. A 40-fold intensity increase for the green
upconversion and a 34-fold intensity increase for the red upconversion were
observed as the cores are coated with three shell layers. The origin of the
upconversion enhancement was studied on the basis of photoluminescence spectra
and decay times. Our results indicate that the upconversion enhancement in the
sandwiched structure mainly originates from the suppression of de-excitation of
Yb(3+) ions. We also explored the population of the Er(3+4)F9/2 level. The
results reveal that energy transfer from the lower intermediate Er(3+4)I13/2
level is dominant for populating the Er(3+4)F9/2 level when the nanocrystal size
is relatively small; however, with increasing nanocrystal size, the contribution
of the green emitting Er(3+4)S3/2 level for populating the Er(3+4)F9/2 level,
which mainly comes from the cross relaxation energy transfer from Er(3+) ions to
Yb(3+) ions followed by energy back transfer within the same Er(3+)-Yb(3+) pair,
becomes more and more important. Moreover, this mechanism takes place only in the
nearest Er(3+)-Yb(3+) pairs. This population route is in good agreement with that
in nanomaterials and bulk materials.
PMID- 25848859
TI - Design and rationale for the randomised, double-blinded, placebo-controlled
Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS)
crossover study.
AB - BACKGROUND: Glucagon-like peptide-1 is an incretin hormone essential for normal
human glucose homeostasis. Expression of the glucagon-like peptide-1 receptor in
the myocardium has fuelled growing interest in the direct and indirect
cardiovascular effects of native glucagon-like peptide-1, its degradation product
glucagon-like peptide-1(9-36), and the synthetic glucagon-like peptide-1 receptor
agonists. Preclinical studies have demonstrated cardioprotective actions of all
three compounds in the setting of experimental myocardial infarction and left
ventricular systolic dysfunction. This has led to Phase 2 trials of native
glucagon-like peptide-1 and incretin-based therapies in humans with and without
Type 2 diabetes mellitus. These studies have demonstrated the ability of glucagon
like peptide-1, independent of glycaemic control, to positively modulate the
metabolic and haemodynamic parameters of individuals with coronary artery disease
and left ventricular systolic dysfunction. We aim to add to this growing body of
evidence by studying the effect of chronic glucagon-like peptide-1 receptor
activation on exercise-induced ischaemia in patients with chronic stable angina
managed conservatively or awaiting revascularisation. The hypothesis being
liraglutide, a subcutaneously injectable glucagon-like peptide-1 receptor
agonist, is able to improve exercise haemodynamics in patients with obstructive
coronary artery disease when compared with saline placebo. METHODS AND DESIGN:
The Liraglutide to Improve corONary haemodynamics during Exercise streSS
(LIONESS) trial is an investigator-initiated single-centre randomised double
blinded placebo-controlled crossover proof-of-principle physiological study.
Primary endpoints are change in rate pressure product at 0.1 mV ST-segment
depression and change in degree of ST-segment depression at peak exercise during
sequential exercise tolerance testing performed over a 6-week study period in
which 26 patients will be randomised to either liraglutide or saline with
crossover to the opposing regimen at week 3. DISCUSSION: The study will be
conducted in accordance with the principles of Good Clinical Practice and the
Declaration of Helsinki. The local Research Ethics Committee and Medicines and
Healthcare Products Regulatory Agency have approved the study. TRIAL
REGISTRATION: National Institute of Health Research Clinical Research Network
(NIHR CRN) Portfolio ID 11112 and ClinicalTrials.gov Identifier NCT02315001.
PMID- 25848861
TI - Multigene prognostic tests in breast cancer: past, present, future.
AB - There is growing consensus that multigene prognostic tests provide useful
complementary information to tumor size and grade in estrogen receptor (ER)
positive breast cancers. The tests primarily rely on quantification of ER and
proliferation-related genes and combine these into multivariate prediction
models. Since ER-negative cancers tend to have higher proliferation rates, the
prognostic value of current multigene tests in these cancers is limited. First
generation prognostic signatures (Oncotype DX, MammaPrint, Genomic Grade Index)
are substantially more accurate to predict recurrence within the first 5 years
than in later years. This has become a limitation with the availability of
effective extended adjuvant endocrine therapies. Newer tests (Prosigna,
EndoPredict, Breast Cancer Index) appear to possess better prognostic value for
late recurrences while also remaining predictive of early relapse. Some clinical
prediction problems are more difficult to solve than others: there are no
clinically useful prognostic signatures for ER-negative cancers, and drug
specific treatment response predictors also remain elusive. Emerging areas of
research involve the development of immune gene signatures that carry modest but
significant prognostic value independent of proliferation and ER status and
represent candidate predictive markers for immune-targeted therapies. Overall
metrics of tumor heterogeneity and genome integrity (for example, homologue
recombination deficiency score) are emerging as potential new predictive markers
for platinum agents. The recent expansion of high-throughput technology platforms
including low-cost sequencing of circulating and tumor-derived DNA and RNA and
rapid reliable quantification of microRNA offers new opportunities to build
extended prediction models across multiplatform data.
PMID- 25848862
TI - Plant diversity increases soil microbial activity and soil carbon storage.
AB - Plant diversity strongly influences ecosystem functions and services, such as
soil carbon storage. However, the mechanisms underlying the positive plant
diversity effects on soil carbon storage are poorly understood. We explored this
relationship using long-term data from a grassland biodiversity experiment (The
Jena Experiment) and radiocarbon ((14)C) modelling. Here we show that higher
plant diversity increases rhizosphere carbon inputs into the microbial community
resulting in both increased microbial activity and carbon storage. Increases in
soil carbon were related to the enhanced accumulation of recently fixed carbon in
high-diversity plots, while plant diversity had less pronounced effects on the
decomposition rate of existing carbon. The present study shows that elevated
carbon storage at high plant diversity is a direct function of the soil microbial
community, indicating that the increase in carbon storage is mainly limited by
the integration of new carbon into soil and less by the decomposition of existing
soil carbon.
PMID- 25848863
TI - FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of
basal-like breast cancer.
AB - INTRODUCTION: Our previous clinical study demonstrated that the under-expression
of FOXF2 is associated with early-onset metastasis and poor prognosis of patients
with triple-negative breast cancer. In this study, we further characterized the
role of FOXF2 in metastasis of basal-like breast cancer (BLBC) and underlying
molecular mechanisms. METHODS: RT-qPCR, immunoblot, immunofluorescence and
immunohistochemistry were performed to assess the expression of genes and
proteins in cell lines and tissues. A series of in vitro and in vivo assays was
performed in the cells with RNAi-mediated knockdown or overexpression to
elucidate the function and transcriptional regulatory role of FOXF2 in breast
cancer. RESULTS: We found that FOXF2 was specifically expressed in most basal
like breast cells. FOXF2 deficiency enhanced the metastatic ability of BLBC cells
in vitro and in vivo. Additionally, FOXF2 deficiency induced the epithelial
mesenchymal transition (EMT) of basal-like breast cells. Furthermore, we
identified that TWIST1 is a transcriptional target of FOXF2. TWIST1 was
negatively regulated by FOXF2 and mediated the FOXF2-regulated EMT phenotype of
basal-like breast cells and aggressive property of BLBC. CONCLUSIONS: FOXF2 is a
novel EMT-suppressing transcription factor in BLBC. FOXF2 deficiency enhances
metastatic ability of BLBC cells by activating the EMT program through
upregulating the transcription of TWIST1.
PMID- 25848864
TI - The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses
and autoimmunity.
AB - The molecules and pathways that fine-tune innate inflammatory responses mediated
by Toll-like receptor 7 (TLR7) remain to be fully elucidated. Using an unbiased
genome-scale screen with short hairpin RNA (shRNA), we identified the receptor
TREML4 as an essential positive regulator of TLR7 signaling. Macrophages from
Treml4(-/-) mice were hyporesponsive to TLR7 agonists and failed to produce type
I interferons due to impaired phosphorylation of the transcription factor STAT1
by the mitogen-activated protein kinase p38 and decreased recruitment of the
adaptor MyD88 to TLR7. TREML4 deficiency reduced the production of inflammatory
cytokines and autoantibodies in MRL/lpr mice, which are prone to systemic lupus
erythematosus (SLE), and inhibited the antiviral immune response to influenza
virus. Our data identify TREML4 as a positive regulator of TLR7 signaling and
provide insight into the molecular mechanisms that control antiviral immunity and
the development of autoimmunity.
PMID- 25848865
TI - Responsiveness of B cells is regulated by the hinge region of IgD.
AB - Mature B cells express immunoglobulin M (IgM)- and IgD-isotype B cell antigen
receptors, but the importance of IgD for B cell function has been unclear. By
using a cellular in vitro system and corresponding mouse models, we found that
antigens with low valence activated IgM receptors but failed to trigger IgD
signaling, whereas polyvalent antigens activated both receptor types.
Investigations of the molecular mechanism showed that deletion of the IgD
specific hinge region rendered IgD responsive to monovalent antigen, whereas
transferring the hinge to IgM resulted in responsiveness only to polyvalent
antigen. Our data suggest that the increased IgD/IgM ratio on conventional B-2
cells is important for preferential immune responses to antigens in immune
complexes, and that the increased IgM expression on B-1 cells is essential for B
1 cell homeostasis and function.
PMID- 25848868
TI - Highly Efficient Heterogeneous Hydroformylation over Rh-Metalated Porous Organic
Polymers: Synergistic Effect of High Ligand Concentration and Flexible Framework.
AB - A series of diphosphine ligand constructed porous polymers with stable and
flexible frameworks have been successfully synthesized under the solvothermal
conditions from polymerizing the corresponding vinyl-functionalized diphosphine
monomers. These insoluble porous polymers can be swollen by a wide range of
organic solvents, showing similar behavior to those of soluble analogues. Rather
than just as immobilizing homogeneous catalysts, these porous polymers supported
with Rh species demonstrate even better catalytic performance in the
hydroformylations than the analogue homogeneous catalysts. The sample
extraordinary performance could be attributed to the combination of high ligand
concentration and flexible framework of the porous polymers. Meanwhile, they can
be easily separated and recycled from the reaction systems without losing any
activity and selectivity. This excellent catalytic performance and easy recycling
heterogeneous catalyst property make them be very attractive. These diphosphine
ligand constructed porous polymers may provide new platforms for the
hydroformylation of olefins in the future.
PMID- 25848866
TI - Rapid linkage of innate immunological signals to adaptive immunity by the brain
fat axis.
AB - Innate immunological signals induced by pathogen- and/or damage-associated
molecular patterns are essential for adaptive immune responses, but it is unclear
if the brain has a role in this process. Here we found that while the abundance
of tumor-necrosis factor (TNF) quickly increased in the brain of mice following
bacterial infection, intra-brain delivery of TNF mimicked bacterial infection to
rapidly increase the number of peripheral lymphocytes, especially in the spleen
and fat. Studies of various mouse models revealed that hypothalamic responses to
TNF were accountable for this increase in peripheral lymphocytes in response to
bacterial infection. Finally, we found that hypothalamic induction of lipolysis
mediated the brain's action in promoting this increase in the peripheral adaptive
immune response. Thus, the brain-fat axis is important for rapid linkage of
innate immunity to adaptive immunity.
PMID- 25848867
TI - Let-7 microRNAs target the lineage-specific transcription factor PLZF to regulate
terminal NKT cell differentiation and effector function.
AB - Lethal-7 (let-7) microRNAs (miRNAs) are the most abundant miRNAs in the genome,
but their role in developing thymocytes is unclear. We found that let-7 miRNAs
targeted Zbtb16 mRNA, which encodes the lineage-specific transcription factor
PLZF, to post-transcriptionally regulate PLZF expression and thereby the effector
functions of natural killer T cells (NKT cells). Dynamic upregulation of let-7
miRNAs during the development of NKT thymocytes downregulated PLZF expression and
directed their terminal differentiation into interferon-gamma (IFN-gamma)
producing NKT1 cells. Without upregulation of let-7 miRNAs, NKT thymocytes
maintained high PLZF expression and terminally differentiated into interleukin 4
(IL-4)-producing NKT2 cells or IL-17-producing NKT17 cells. Upregulation of let-7
miRNAs in developing NKT thymocytes was signaled by IL-15, vitamin D and retinoic
acid. Such targeting of a lineage-specific transcription factor by miRNA
represents a previously unknown level of developmental regulation in the thymus.
PMID- 25848869
TI - Local-global overlap in diversity informs mechanisms of bacterial biogeography.
AB - Spatial variation in environmental conditions and barriers to organism movement
are thought to be important factors for generating endemic species, thus
enhancing global diversity. Recent microbial ecology research suggested that the
entire diversity of bacteria in the global oceans could be recovered at a single
site, thus inferring a lack of bacterial endemism. We argue this is not the case
in the global ocean, but might be in other bacterial ecosystems with higher
dispersal rates and lower global diversity, like the human gut. We quantified the
degree to which local and global bacterial diversity overlap in a diverse set of
ecosystems. Upon comparison of observed local-global diversity overlap with
predictions from a neutral biogeography model, human-associated microbiomes (gut,
skin, mouth) behaved much closer to neutral expectations whereas soil, lake and
marine communities deviated strongly from the neutral expectations. This is
likely a result of differences in dispersal rate among 'patches', global
diversity of these systems, and local densities of bacterial cells. It appears
that overlap of local and global bacterial diversity is surprisingly large (but
likely not one-hundred percent), and most importantly this overlap appears to be
predictable based upon traditional biogeographic parameters like community size,
global diversity, inter-patch environmental heterogeneity and patch connectivity.
PMID- 25848870
TI - Rapid selective sweep of pre-existing polymorphisms and slow fixation of new
mutations in experimental evolution of Desulfovibrio vulgaris.
AB - To investigate the genetic basis of microbial evolutionary adaptation to salt
(NaCl) stress, populations of Desulfovibrio vulgaris Hildenborough (DvH), a
sulfate-reducing bacterium important for the biogeochemical cycling of sulfur,
carbon and nitrogen, and potentially the bioremediation of toxic heavy metals and
radionuclides, were propagated under salt stress or non-stress conditions for
1200 generations. Whole-genome sequencing revealed 11 mutations in salt stress
evolved clone ES9-11 and 14 mutations in non-stress-evolved clone EC3-10. Whole
population sequencing data suggested the rapid selective sweep of the pre
existing polymorphisms under salt stress within the first 100 generations and the
slow fixation of new mutations. Population genotyping data demonstrated that the
rapid selective sweep of pre-existing polymorphisms was common in salt stress
evolved populations. In contrast, the selection of pre-existing polymorphisms was
largely random in EC populations. Consistently, at 100 generations, stress
evolved population ES9 showed improved salt tolerance, namely increased growth
rate (2.0-fold), higher biomass yield (1.8-fold) and shorter lag phase (0.7-fold)
under higher salinity conditions. The beneficial nature of several mutations was
confirmed by site-directed mutagenesis. All four tested mutations contributed to
the shortened lag phases under higher salinity condition. In particular, compared
with the salt tolerance improvement in ES9-11, a mutation in a histidine kinase
protein gene lytS contributed 27% of the growth rate increase and 23% of the
biomass yield increase while a mutation in hypothetical gene DVU2472 contributed
24% of the biomass yield increase. Our results suggested that a few beneficial
mutations could lead to dramatic improvements in salt tolerance.
PMID- 25848871
TI - The diversity and host interactions of Propionibacterium acnes bacteriophages on
human skin.
AB - The viral population, including bacteriophages, is an important component of the
human microbiota, yet is poorly understood. We aim to determine whether
bacteriophages modulate the composition of the bacterial populations, thus
potentially playing a role in health or disease. We investigated the diversity
and host interactions of the bacteriophages of Propionibacterium acnes, a major
human skin commensal implicated in acne pathogenesis. By sequencing 48 P. acnes
phages isolated from acne patients and healthy individuals and by analyzing the
P. acnes phage populations in healthy skin metagenomes, we revealed that P. acnes
phage populations in the skin microbial community are often dominated by one
strain. We also found phage strains shared among both related and unrelated
individuals, suggesting that a pool of common phages exists in the human
population and that transmission of phages may occur between individuals. To
better understand the bacterium-phage interactions in the skin microbiota, we
determined the outcomes of 74 genetically defined Propionibacterium strains
challenged by 15 sequenced phages. Depending on the Propionibacterium lineage,
phage infection can result in lysis, pseudolysogeny, or resistance. In type II P.
acnes strains, we found that encoding matching clustered regularly interspaced
short palindromic repeat spacers is insufficient to confer phage resistance.
Overall, our findings suggest that the prey-predator relationship between
bacteria and phages may have a role in modulating the composition of the
microbiota. Our study also suggests that the microbiome structure of an
individual may be an important factor in the design of phage-based therapy.
PMID- 25848872
TI - Response of Prochlorococcus to varying CO2:O2 ratios.
AB - Carbon fixation has a central role in determining cellular redox poise,
increasingly understood to be a key parameter in cyanobacterial physiology. In
the cyanobacterium Prochlorococcus-the most abundant phototroph in the
oligotrophic oceans-the carbon-concentrating mechanism is reduced to the bare
essentials. Given the ability of Prochlorococcus populations to grow under a wide
range of oxygen concentrations in the ocean, we wondered how carbon and oxygen
physiology intersect in this minimal phototroph. Thus, we examined how CO2:O2 gas
balance influenced growth and chlorophyll fluorescence in Prochlorococcus strain
MED4. Under O2 limitation, per-cell chlorophyll fluorescence fell at all CO2
levels, but still permitted substantial growth at moderate and high CO2. Under
CO2 limitation, we observed little growth at any O2 level, although per-cell
chlorophyll fluorescence fell less sharply when O2 was available. We explored
this pattern further by monitoring genome-wide transcription in cells shocked
with acute limitation of CO2, O2 or both. O2 limitation produced much smaller
transcriptional changes than the broad suppression seen under CO2 limitation and
CO2/O2 co-limitation. Strikingly, both CO2 limitation conditions initially evoked
a transcriptional response that resembled the pattern previously seen in high
light stress, but at later timepoints we observed O2-dependent recovery of
photosynthesis-related transcripts. These results suggest that oxygen has a
protective role in Prochlorococcus when carbon fixation is not a sufficient sink
for light energy.
PMID- 25848873
TI - Single-cell genomics-based analysis of virus-host interactions in marine surface
bacterioplankton.
AB - Viral infections dynamically alter the composition and metabolic potential of
marine microbial communities and the evolutionary trajectories of host
populations with resulting feedback on biogeochemical cycles. It is quite
possible that all microbial populations in the ocean are impacted by viral
infections. Our knowledge of virus-host relationships, however, has been limited
to a minute fraction of cultivated host groups. Here, we utilized single-cell
sequencing to obtain genomic blueprints of viruses inside or attached to
individual bacterial and archaeal cells captured in their native environment,
circumventing the need for host and virus cultivation. A combination of
comparative genomics, metagenomic fragment recruitment, sequence anomalies and
irregularities in sequence coverage depth and genome recovery were utilized to
detect viruses and to decipher modes of virus-host interactions. Members of all
three tailed phage families were identified in 20 out of 58 phylogenetically and
geographically diverse single amplified genomes (SAGs) of marine bacteria and
archaea. At least four phage-host interactions had the characteristics of late
lytic infections, all of which were found in metabolically active cells. One
virus had genetic potential for lysogeny. Our findings include first known
viruses of Thaumarchaeota, Marinimicrobia, Verrucomicrobia and
Gammaproteobacteria clusters SAR86 and SAR92. Viruses were also found in SAGs of
Alphaproteobacteria and Bacteroidetes. A high fragment recruitment of viral
metagenomic reads confirmed that most of the SAG-associated viruses are abundant
in the ocean. Our study demonstrates that single-cell genomics, in conjunction
with sequence-based computational tools, enable in situ, cultivation-independent
insights into host-virus interactions in complex microbial communities.
PMID- 25848874
TI - Single-cell genomics of a rare environmental alphaproteobacterium provides unique
insights into Rickettsiaceae evolution.
AB - The bacterial family Rickettsiaceae includes a group of well-known etiological
agents of many human and vertebrate diseases, including epidemic typhus-causing
pathogen Rickettsia prowazekii. Owing to their medical relevance, rickettsiae
have attracted a great deal of attention and their host-pathogen interactions
have been thoroughly investigated. All known members display obligate
intracellular lifestyles, and the best-studied genera, Rickettsia and Orientia,
include species that are hosted by terrestrial arthropods. Their obligate
intracellular lifestyle and host adaptation is reflected in the small size of
their genomes, a general feature shared with all other families of the
Rickettsiales. Yet, despite that the Rickettsiaceae and other Rickettsiales
families have been extensively studied for decades, many details of the origin
and evolution of their obligate host-association remain elusive. Here we report
the discovery and single-cell sequencing of 'Candidatus Arcanobacter lacustris',
a rare environmental alphaproteobacterium that was sampled from Damariscotta Lake
that represents a deeply rooting sister lineage of the Rickettsiaceae.
Intriguingly, phylogenomic and comparative analysis of the partial 'Candidatus
Arcanobacter lacustris' genome revealed the presence chemotaxis genes and
vertically inherited flagellar genes, a novelty in sequenced Rickettsiaceae, as
well as several host-associated features. This finding suggests that the ancestor
of the Rickettsiaceae might have had a facultative intracellular lifestyle. Our
study underlines the efficacy of single-cell genomics for studying microbial
diversity and evolution in general, and for rare microbial cells in particular.
PMID- 25848875
TI - Size-fraction partitioning of community gene transcription and nitrogen
metabolism in a marine oxygen minimum zone.
AB - The genetic composition of marine microbial communities varies at the microscale
between particle-associated (PA; >1.6 MUm) and free-living (FL; 0.2-1.6 MUm)
niches. It remains unclear, however, how metabolic activities differ between PA
and FL fractions. We combined rate measurements with metatranscriptomics to
quantify PA and FL microbial activity in the oxygen minimum zone (OMZ) of the
Eastern Tropical North Pacific, focusing on dissimilatory processes of the
nitrogen (N) cycle. Bacterial gene counts were 8- to 15-fold higher in the FL
compared with the PA fraction. However, rates of all measured N cycle processes,
excluding ammonia oxidation, declined significantly following particle (>1.6 MUm)
removal. Without particles, rates of nitrate reduction to nitrite (1.5-9.4nMNd(
1)) fell to zero and N2 production by denitrification (0.5-1.7nMNd(-1)) and
anammox (0.3-1.9nMNd(-1)) declined by 53-85%. The proportional representation of
major microbial taxa and N cycle gene transcripts in metatranscriptomes followed
fraction-specific trends. Transcripts encoding nitrate reductase were uniform
among PA and FL fractions, whereas anammox-associated transcripts were
proportionately enriched up to 15-fold in the FL fraction. In contrast,
transcripts encoding enzymes for N2O and N2 production by denitrification were
enriched up to 28-fold in PA samples. These patterns suggest that the majority of
N cycle activity, excluding N2O and N2 production by denitrification, is confined
to a FL majority that is critically dependent on access to particles, likely as a
source of organic carbon and inorganic N. Variable particle distributions may
drive heterogeneity in N cycle activity and gene expression in OMZs.
PMID- 25848877
TI - Acute kidney injury: Mitsugumin 53 mediates repair of the damaged proximal
tubular epithelium.
PMID- 25848876
TI - Growth phase-specific evolutionary benefits of natural transformation in
Acinetobacter baylyi.
AB - Natural transformation in bacteria facilitates the uptake and genomic integration
of exogenous DNA. This allows horizontal exchange of adaptive traits not easily
achieved by point mutations, and has a major role in the acquisition of adaptive
traits exemplified by antibiotic resistance determinants and vaccination escape.
Mechanisms of DNA uptake and genomic integration are well described for several
naturally transformable bacterial species; however, the selective forces
responsible for its evolution and maintenance are still controversial. In this
study we evolved transformation-proficient and -deficient Acinetobacter baylyi
for 175 days in serial transfer cultures where stress was included. We found that
natural transformation-proficient populations adapted better to active growth and
early stationary phase. This advantage was offset by the reduced performance in
the late stationary/death phase. We demonstrate fitness trade-offs between
adaptation to active growth and survival in stationary/death phase caused by
antagonistic pleiotropy. The presented data suggest that the widely held
assumption that recombination speeds up adaptation by rapid accumulation of
multiple adaptive mutations in the same genetic background is not sufficient to
fully account for the maintenance of natural transformation in bacteria.
PMID- 25848878
TI - Glomerular disease: Efficacy of corticosteroids in high-risk IgA nephropathy.
PMID- 25848879
TI - Genetics: Strong association of APOL1 risk variants with HIV-associated
nephropathy in black South Africans.
PMID- 25848880
TI - Hypertension: Impact of blood pressure lowering in type 2 diabetes.
PMID- 25848882
TI - Random-Coil Behavior of Chemically Denatured Topologically Knotted Proteins
Revealed by Small-Angle X-ray Scattering.
AB - Recent studies on the mechanisms by which topologically knotted proteins attain
their natively knotted structures have intrigued theoretical and experimental
biophysicists. Of particular interest is the finding that YibK and YbeA, two
small trefoil knotted proteins, remain topologically knotted in their chemically
denatured states. Using small-angle X-ray scattering (SAXS), we examine whether
these chemically denatured knotted proteins are different from typical random
coils. By revisiting the scaling law of radius of gyration (Rg) as a function of
polypeptide chain length for chemically denatured proteins and natively folded
proteins, we find that the chemically denatured knotted proteins in fact follow
the same random coil-like behavior, suggesting that the formation of topological
protein knots do not necessarily require global compaction while the loosely
knotted polypeptide chains are capable of maintaining the correct chirality
without defined secondary or tertiary structures.
PMID- 25848881
TI - Haemodialysis-induced hypoglycaemia and glycaemic disarrays.
AB - In patients with diabetes receiving chronic haemodialysis, both very high and low
glucose levels are associated with poor outcomes, including mortality. Conditions
that are associated with an increased risk of hypoglycaemia in these patients
include decreased gluconeogenesis in the remnant kidneys, deranged metabolic
pathways, inadequate nutrition, decreased insulin clearance, glucose loss to the
dialysate and diffusion of glucose into erythrocytes during haemodialysis.
Haemodialysis-induced hypoglycaemia is common during treatments with glucose-free
dialysate, which engenders a catabolic status similar to fasting; this state can
also occur with 5.55 mmol/l glucose-containing dialysate. Haemodialysis-induced
hypoglycaemia occurs more frequently in patients with diabetes than in those
without. Insulin therapy and oral hypoglycaemic agents should, therefore, be used
with caution in patients on dialysis. Several hours after completion of
haemodialysis treatment a paradoxical rebound hyperglycaemia may occur via a
similar mechanism as the Somogyi effect, together with insulin resistance.
Appropriate glycaemic control tailored for patients on haemodialysis is needed to
avoid haemodialysis-induced hypoglycaemia and other glycaemic disarrays. In this
Review we summarize the pathophysiology and current management of glycaemic
disarrays in patients on haemodialysis.
PMID- 25848883
TI - High definition bronchoscopy: a randomized exploratory study of diagnostic value
compared to standard white light bronchoscopy and autofluorescence bronchoscopy.
AB - BACKGROUND: Videobronchoscopy is an essential diagnostic procedure for evaluation
of the central airways and pivotal for the diagnosis and staging of lung cancer.
Technological improvements have resulted in high definition (HD) images with
advanced real time image enhancement techniques (i-scan). OBJECTIVES: In this
study we aimed to explore the sensitivity of HD+ i-scan bronchoscopy for
detection of epithelial changes like vascular abnormalities and suspicious
preinvasive lesions, and tumors. METHODS: In patients scheduled for a therapeutic
or diagnostic procedure under general anesthesia videos of the bronchial tree
were made using 5 videobronchoscopy modes in random order: normal white light
videobronchoscopy (WLB), HD-bronchoscopy (HD), HD bronchoscopy with surface
enhancement technique (i-scan1), HD with surface- and tone enhancement technique
(i-scan2) and dual mode autofluorescence videobronchoscopy (AFB). The videos were
scored in random order by two independent and blinded expert bronchoscopists.
RESULTS: In 29 patients all videos were available for analysis. Vascular
abnormalities were scored most frequently in HD + i-scan2 bronchoscopy (1.33 +/-
0.29 abnormal or suspicious sites per patient) as compared to 0.12 +/- 0.05 site
for AFB (P = 0.003). Sites suspicious for preinvasive lesions were most
frequently reported using AFB (0.74 +/- 0.12 sites per patient) as compared to
0.17 +/- 0.06 for both WLB and HD bronchoscopy (P = 0.003). Tumors were detected
equally by all modalities. The preferred modality was HD bronchoscopy with i-scan
(tone- plus surface and surface enhancement in respectively 38% and 35% of cases
P = 0.006). CONCLUSIONS: This study shows that high definition bronchoscopy with
image enhancement technique may result in better detection of subtle vascular
abnormalities in the airways. Since these abnormalities may be related to
preneoplastic lesions and tumors this is of clinical relevance. Further
investigations using this technique relating imaging to histology are warranted.
PMID- 25848885
TI - Detection of endogenous and food-derived collagen dipeptide prolylhydroxyproline
(Pro-Hyp) in allergic contact dermatitis-affected mouse ear.
AB - Generation of collagen dipeptides and deposition of orally administered
prolylhydroxyproline (Pro-Hyp) in local inflammatory sites were examined in mice
with hapten (2,4-dinitrofluorobenzene)-induced dermatitis in the ear. Pro-Hyp
content in the hapten-treated ear was significantly higher in the chronic phase
of contact dermatitis than the vehicle control. In contrast, hydroxyprolylglycine
contents remained at lower levels in all cases compared to Pro-Hyp. Four hours
after the ingestion of [(13)C5,(15)N]Pro and [(13)C5,(15)N]Pro-Hyp, labeled-Pro
Hyp and Pro, respectively, appeared only in the ear with dermatitis. Thus, Pro
Hyp is generated and degraded as part of the rapid synthesis and degradation of
collagen in the ear with dermatitis. In addition to the endogenously generated
Pro-Hyp, the orally administered Pro-Hyp was deposited in the ears.
PMID- 25848886
TI - Is art therapy a reliable tool for rehabilitating people suffering from
brain/mental diseases?
AB - Whether art therapy can be an effective rehabilitative treatment for people with
brain or mental diseases (e.g., dementia, Alzheimer's disease, Parkinson's
disease, autism, schizophrenia) is a long-standing and highly debated issue. On
the one hand, several observational studies and anecdotal evidence
enthusiastically support the effectiveness of arts-based therapy. On the other
hand, few rigorous clinical investigations have been performed, and there is too
little empirical evidence to allow a full assessment of the risks and benefits of
this intervention. Nevertheless, there is a progressively increasing demand for
the development of appropriate complementary therapies to improve the personal
and social lives of patients with neurodegenerative diseases. This is because
conventional medical treatments are aimed at alleviating symptoms but cannot
arrest or reverse the degenerative process. Thus, as disease progresses and
adverse effects emerge, patients' quality of life dramatically decreases; when
this occurs patients seek different forms of intervention. Art therapy is a
potentially appealing treatment because of its more holistic approach to
healthcare. However, as with any medicine, its effects must be tested by using
standard, rigorous scientific approaches. This report describes the current state
of research into art therapy and outlines many key factors that future research
should consider, all of which are directly or indirectly related to the neural
mechanism underlying behavioral changes: brain plasticity. Artistic performance
could promote some form of brain plasticity that, to some extent, might
compensate for the brain damage caused by the disease.
PMID- 25848884
TI - Pleiotropic effect of chromosome 5A and the mvp mutation on the metabolite
profile during cold acclimation and the vegetative/generative transition in
wheat.
AB - BACKGROUND: Wheat is the leading source of vegetable protein in the human diet,
and metabolites are crucial for both plant development and human nutrition. The
recent advances in metabolomics provided an opportunity to perform an untargeted
metabolite analysis in this important crop. RESULTS: Wheat was characterised at
the metabolite level during cold acclimation and transition from the vegetative
to the generative phase. The relationship between these changes and chromosome 5A
and the maintained vegetative phase (mvp) mutation was also investigated. Samples
were taken from the shoots and crowns during four developmental stages: plants
grown at 20/17 degrees C, after cold treatment but still during the vegetative
phase, at the double ridge and during spikelet formation. The levels of 47
compounds were identified by gas chromatography-mass spectrometry, of which 38
were annotated. The cold treatment, in general, increased the concentrations of
osmolites but not in all lines and not equally in the shoots and crowns. The
accumulation of proline was not associated with the vernalisation process or with
frost tolerance. The mvp mutation and chromosome 5A substitutions altered the
amounts of several metabolites compared to those of the Tm and CS, respectively,
during each developmental stage. The Ch5A substitution resulted in more
substantial changes at the metabolite level than did the Tsp5A substitution.
While Ch5A mainly influenced the sugar concentrations, Tsp5A altered the level of
tricarboxylic acid cycle intermediates during the vegetative/generative
transition. A much higher trehalose, proline, glutamine, asparagine, and
unidentified m/z 186 content was detected in crowns than in shoots that may
contribute to the frost tolerance of crowns. CONCLUSIONS: Substantial influences
of chromosome 5A and the mvp mutation on metabolism during four different
developmental stages were demonstrated. The distinct and overlapping accumulation
patterns of metabolites suggest the complex genetic regulation of metabolism in
the shoots and crowns.
PMID- 25848888
TI - Regenerable fluorescent nanosensors for monitoring and recovering metal ions
based on photoactivatable monolayer self-assembly and host-guest interactions.
AB - Efficient detection, removal, and recovery of heavy metal ions from aqueous
environments represents a technologically challenging and ecologically urgent
question in the face of increasing metal-related pollution and poisoning across
the globe. Although small-molecule and entrapment-based nanoparticle sensors have
been extensively explored for metal detection, neither of these extant strategies
satisfies the critical needs for high-performance sensors that are inexpensive,
efficient, and recyclable. Here we first report the development of a regenerable
fluorescent nanosensor system for the selective and sensitive detection of
multiple heavy metal ions, based on light-switchable monolayer self-assembly and
host-guest interactions. The system exploits photocontrolled inclusion and
exclusion responses of an alpha-cyclodextrin (CD)-containing surface conjugated
with photoisomerizable azobenzene as a supramolecular system that undergoes
reversible assembly and disassembly. The metal nanosensors can be facilely
fabricated and photochemically switched between three chemically distinct
entities, each having an excellent capacity for selective detecting specific
metal ions (namely, Cu(2+), Fe(3+), Hg(2+)) in a chemical system and in assays on
actual water samples with interfering contaminants.
PMID- 25848887
TI - Anticancer and antiangiogenic activity of surfactant-free nanoparticles based on
self-assembled polymeric derivatives of vitamin E: structure-activity
relationship.
AB - alpha-Tocopheryl succinate (alpha-TOS) is a well-known mitochondrially targeted
anticancer compound, however, it is highly hydrophobic and toxic. In order to
improve its activity and reduce its toxicity, new surfactant-free biologically
active nanoparticles (NP) were synthesized. A methacrylic derivative of alpha-TOS
(MTOS) was prepared and incorporated in amphiphilic pseudoblock copolymers when
copolymerized with N-vinylpyrrolidone (VP) by free radical polymerization
(poly(VP-co-MTOS)). The selected poly(VP-co-MTOS) copolymers formed surfactant
free NP by nanoprecipitation with sizes between 96 and 220 nm and narrow size
distribution, and the in vitro biological activity was tested. In order to
understand the structure-activity relationship three other methacrylic monomers
were synthesized and characterized: MVE did not have the succinate group, SPHY
did not have the chromanol ring, and MPHY did not have both the succinate group
and the chromanol ring. The corresponding families of copolymers (poly(VP-co
MVE), poly(VP-co-SPHY), and poly(VP-co-MPHY)) were synthesized and characterized,
and their biological activity was compared to poly(VP-co-MTOS). Both poly(VP-co
MTOS) and poly(VP-co-MVE) presented triple action: reduced cell viability of
cancer cells with little or no harm to normal cells (anticancer), reduced
viability of proliferating endothelial cells with little or no harm to quiescent
endothelial cells (antiangiogenic), and efficiently encapsulated hydrophobic
molecules (nanocarrier). The anticancer and antiangiogenic activity of the
synthesized copolymers is demonstrated as the active compound (vitamin E or alpha
tocopheryl succinate) do not need to be cleaved to trigger the biological action
targeting ubiquinone binding sites of complex II. Poly(VP-co-SPHY) and poly(VP-co
MPHY) also formed surfactant-free NP that were also endocyted by the assayed
cells; however, these NP did not selectively reduce cell viability of cancer
cells. Therefore, the chromanol ring of the vitamin E analogues has an important
role in the biological activity of the copolymers. Moreover, when succinate
moiety is substituted and vitamin E is directly linked to the macromolecular
chain through an ester bond, the biological activity is maintained.
PMID- 25848889
TI - Phototropism in gametophytic shoots of the moss Physcomitrella patens.
AB - Shoot phototropism enables plants to position their photosynthetic organs in
favorable light conditions and thus benefits growth and metabolism in land
plants. To understand the evolution of this response, we established an
experimental system to study phototropism in gametophores of the moss
Physcomitrella patens. The phototropic response of gametophores occurs slowly; a
clear response takes place more than 24 hours after the onset of unilateral light
irradiation, likely due to the slow growth rate of gametophores. We also found
that red and far-red light can induce phototropism, with blue light being less
effective. These results suggest that plants used a broad range of light
wavelengths as phototropic signals during the early evolution of land plants.
PMID- 25848890
TI - Antioxidant vitamin C prevents decline in endothelial function during sitting.
AB - BACKGROUND: This study was designed to test the hypothesis that antioxidant
Vitamin C prevents the impairment of endothelial function during prolonged
sitting. MATERIAL AND METHODS: Eleven men (24.2 +/- 4.4 yrs) participated in 2
randomized 3-h sitting trials. In the sitting without vitamin C (SIT) and the
sitting with vitamin C (VIT) trial, participants were seated for 3 h without
moving their legs. Additionally, in the VIT trial, participants ingested 2
vitamin C tablets (1 g and 500 mg) at 30 min and 1 h 30 min, respectively.
Superficial femoral artery (SFA) flow-mediated dilation (FMD) was measured hourly
for 3 h. RESULTS: By a 1-way ANOVA, there was a significant decline in FMD during
3 h of SIT (p<0.001). Simultaneously, there was a significant decline in
antegrade (p=0.04) and mean (0.037) shear rates. For the SIT and VIT trials by a
2-way (trial x time) repeated measures ANOVA, there was a significant interaction
(p=0.001). Pairwise testing revealed significant between-SFA FMD in the SIT and
VIT trial at each hour after baseline, showing that VIT prevented the decline in
FMD 1 h (p=0.009), 2 h (p=0.016), and 3 h (p=0.004). There was no difference in
the shear rates between SIT and VIT trials (p>0.05). CONCLUSIONS: Three hours of
sitting resulted in impaired SFA FMD. Antioxidant Vitamin C prevented the decline
in SFA FMD, suggesting that oxidative stress may contribute to the impairment in
endothelial function during sitting.
PMID- 25848891
TI - Phytoremediation of Cd, Ni, Pb and Zn by Salvinia minima.
AB - Most metals disperse easily in environments and can be bioconcentrated in tissues
of many organisms causing risks to the health and stability of aquatic ecosystems
even at low concentrations. The use of plants to phytoremediation has been
evaluated to mitigate the environmental contamination by metals since they have
large capacity to adsorb or accumulate these elements. In this study we evaluate
Salvinia minima growth and its ability to accumulate metals. The plants were
cultivated for about 60 days in different concentrations of Cd, Ni, Pb and Zn
(tested alone) in controlled environmental conditions and availability of
nutrients. The results indicated that S. minima was able to grow in low
concentrations of selected metals (0.03 mg L(-1) Cd, 0.40 mg L(-1) Ni, 1.00 mg L(
1) Pb and 1.00 mg L(-1) Zn) and still able to adsorb or accumulate metals in
their tissues when cultivated in higher concentrations of selected metals without
necessarily grow. The maximum values of removal metal rates (mg m(2) day(-1)) for
each metal (Cd = 0.0045, Ni = 0.0595, Pb = 0.1423 e Zn = 0.4046) are listed. We
concluded that S. minima may be used as an additional tool for metals removal
from effluent.
PMID- 25848892
TI - The Function of Matricellular Proteins in the Lamina Cribrosa and Trabecular
Meshwork in Glaucoma.
AB - PURPOSE: To review the current literature regarding the role of matricellular
proteins in glaucoma, specifically in the lamina cribrosa (LC) region of the
optic nerve head (ONH) and the trabecular meshwork (TM). METHODS: A literature
search was performed for published articles describing the expression and
function of matricellular proteins such as thrombospondin (TSP), connective
tissue growth factor (CTGF), secreted protein acidic and rich in cysteine
(SPARC), and periostin in glaucoma. RESULTS: In glaucoma, there are
characteristic extracellular matrix (ECM) changes associated with optic disc
cupping in the ONH and subsequent visual field defects. Matricellular proteins
are a family of nonstructural secreted glycoproteins, which enable cells to
communicate with their surrounding ECM, including CTGF, also known as CCN2, TSPs,
SPARC, periostin, osteonectin, and tenascin-C and -X, and other ECM proteins.
Such proteins appear to play a role in fibrosis and increased ECM deposition.
Importantly, most are widely expressed in tissues particularly in the TM and ONH,
and deficiency of TSP1 and SPARC has been shown to lower intraocular pressure in
mouse models of glaucoma through enhanced outflow facility. CONCLUSION: This
article highlights the role of matricellular proteins in glaucoma pathology. The
potential role of these proteins in glaucoma is emerging as some have an
association with the pathophysiology of the TM and LC region and might therefore
be potential targets for therapeutic intervention in glaucoma.
PMID- 25848893
TI - Neuromuscular Fatigue and Muscle Damage After a Women's Rugby Sevens Tournament.
AB - PURPOSE: To examine relationships between on-field game movement patterns and
changes in markers of neuromuscular fatigue and muscle damage during a 2-d
women's rugby sevens tournament. METHODS: Female national (mean +/- SD n = 12,
22.3 +/- 2.5 y, 1.67 +/- 0.04 m, 65.8 +/- 4.6 kg) and state (n = 10, 24.4 +/- 4.3
y, 1.67 +/- 0.03 m, 66.1 +/- 7.9 kg) representative players completed baseline
testing for lower-body neuromuscular function (countermovement-jump [CMJ] test),
muscle damage (capillary creatine kinase [CK]), perceived soreness, and perceived
recovery. Testing was repeated after games on days 1 and 2 of the tournament. GPS
(5-Hz) data were collected throughout the tournament (4-6 games/player). RESULTS:
National players were involved in greater on-field movements for total time,
distance, high-speed running (>5 m/s), and impacts >10 g (effect size [ES] = 0.55
0.97) and displayed a smaller decrement in performance from day 1 to day 2.
Despite this, state players had a much greater 4-fold increase (deltaCK = 737
U/L) in CK compared with the 2-fold increase (deltaCK = 502 U/L) in national
players (ES = 0.73). Both groups had similar perceived soreness and recovery
while CMJ performance was unchanged. High-speed running and impacts >10 g were
largely correlated (r = .66-.91) with deltaCK for both groups. CONCLUSION: A 2
day women's rugby sevens tournament elicits substantial muscle damage; however,
there was little change in lower-body neuromuscular function. Modest increases in
CK can largely be attributed to high-speed running and impacts >10 g that players
typically endure.
PMID- 25848894
TI - The transcriptome of Utricularia vulgaris, a rootless plant with minimalist
genome, reveals extreme alternative splicing and only moderate sequence
similarity with Utricularia gibba.
AB - BACKGROUND: The species of Utricularia attract attention not only owing to their
carnivorous lifestyle, but also due to an elevated substitution rate and a
dynamic evolution of genome size leading to its dramatic reduction. To better
understand the evolutionary dynamics of genome size and content as well as the
great physiological plasticity in this mostly aquatic carnivorous genus, we
analyzed the transcriptome of Utricularia vulgaris, a temperate species with well
characterized physiology and ecology. We compared its transcriptome, namely gene
content and overall transcript profile, with a previously described transcriptome
of Utricularia gibba, a congener possessing one of the smallest angiosperm
genomes. RESULTS: We sequenced a normalized cDNA library prepared from total RNA
extracted from shoots of U. vulgaris including leaves and traps, cultivated under
sterile or outdoor conditions. 454 pyrosequencing resulted in more than 1,400,000
reads which were assembled into 41,407 isotigs in 19,522 isogroups. We observed
high transcript variation in several isogroups explained by multiple loci and/or
alternative splicing. The comparison of U. vulgaris and U. gibba transcriptomes
revealed a similar distribution of GO categories among expressed genes, despite
the differences in transcriptome preparation. We also found a strong
correspondence in the presence or absence of root-associated genes between the U.
vulgaris transcriptome and U. gibba genome, which indicated that the loss of some
root-specific genes had occurred before the divergence of the two rootless
species. CONCLUSIONS: The species-rich genus Utricularia offers a unique
opportunity to study adaptations related to the environment and carnivorous habit
and also evolutionary processes responsible for considerable genome reduction. We
show that a transcriptome may approximate the genome for gene content or gene
duplication estimation. Our study is the first comparison of two global sequence
data sets in Utricularia.
PMID- 25848895
TI - Upward communication about cancer screening: adolescent daughter to mother.
AB - Substantial breast and cervical cancer disparities exist in the United States,
particularly among African American women with low socioeconomic status. There is
considerable potential for discussions about cancer prevention between mothers
and daughters. However, upward communication, from child to parent, remains a
relatively novel research area, and it remains unclear how receptive mothers
would be to messages from their daughter about cancer, a topic that may be
considered culturally inappropriate for daughters to initiate. In this study, the
authors simulated cancer message delivery to daughters and then conducted direct
observation of daughters as they recalled and shared the message with their
mother or female elder. The authors found that daughters were able to
successfully recall and deliver a cancer appeal to their mother and mothers were
generally receptive to this message. Not only did mothers listen to their
daughters' appeals, but also daughters' knowledge of cancer was considerably
improved by the opportunity to educate her female elder. Moreover, daughters'
nonverbal communication suggested a surprisingly relaxed demeanor. The potential
of young people to have an effect on the screening behavior of their female
elders is very promising in terms of reducing cancer disparities.
PMID- 25848897
TI - Efficacy and Safety of Radiofrequency Ablation for Treatment of Locally Recurrent
Thyroid Cancers Smaller than 2 cm.
AB - PURPOSE: To evaluate the efficacy and safety of radiofrequency ablation (RFA) for
localized small recurrent thyroid cancers less than 2 cm by comparing them with
those at repeat surgery. MATERIALS AND METHODS: This retrospective study was
institutional review board-approved, and informed consent was waived. From
December 2008 to December 2011, this study evaluated 73 patients (17 men and 56
women; age, 50.3 years +/- 13.6) with recurrent thyroid cancer who had been
treated with RFA (n = 27) or repeat surgery (n = 46) who met the following
criteria: (a) three or fewer recurrences or lesions with high probability of
recurrence at ultrasonography; (b) no tumor other than the target tumors; and (c)
at least 1 year of follow-up. RFA was recommended and performed in cases of
surgical ineligibility, such as patient refusal and poor medical condition.
Recurrence-free survival rates and posttreatment complication rates (eg,
hoarseness and hypocalcemia) were compared between RFA and reoperation groups
after adjustment with weighted analysis by using inverse probability of treatment
weights. RESULTS: After this adjustment, the 1- and 3-year recurrence-free
survival rates were comparable (P = .681) for RFA (96.0% and 92.6%, respectively)
and reoperation (92.2% and 92.2%, respectively) groups. The posttreatment
hoarseness rate did not differ between the RFA (7.3% [1.8 of 24]) and reoperation
(9.0% [3.6 of 39.5]) groups (P = .812), and posttreatment hypocalcemia occurred
exclusively in the reoperation group (11.6% [4.6 of 39.5]) but not in the RFA
group (0% [0 of 24]) (P = .083). CONCLUSION: RFA may be an effective and safe
alternative to repeat surgery in patients with locally recurrent small thyroid
cancers.
PMID- 25848898
TI - Integrated FDG PET/MR Imaging for the Assessment of Myocardial Salvage in
Reperfused Acute Myocardial Infarction.
AB - PURPOSE: To compare the size of the area with reduced myocardial
fluorodeoxygluose (FDG) uptake with the endocardial surface area (ESA) method as
a marker for the area at risk in patients with reperfused acute myocardial
infarction. MATERIALS AND METHODS: The study was approved by the local
institutional review board. All patients gave written informed consent prior to
their examination. Twenty-five patients (mean age +/- standard deviation, 54
years +/- 14) underwent prospective cardiac positron emission tomography/magnetic
resonance imaging after acute coronary occlusion and interventional reperfusion.
On late gadolinium contrast enhancement images, the size of infarction and the
area at risk, as determined with ESA, were assessed and compared with the area of
reduced FDG uptake. Statistical analysis comprised paired t tests and Mann
Whitney U tests, as well as Pearson r and Spearman rho for correlations. RESULTS:
In patients with infarcted myocardium and reduced FDG uptake (n = 18), a good
correlation between the area of reduced FDG uptake and the area at risk according
to ESA was observed (r = .70, P = .001). The area of reduced FDG uptake (31% +/-
11 of left ventricular myocardial mass) was larger than the size of the infarct
(10% +/- 10, P < .0001) and the area at risk according to ESA (17% +/- 13, P <
.0001). In six patients, no late contrast enhancement was seen, whereas all
patients had an area of reduced FDG uptake (29% +/- 8) in the perfusion territory
of the culprit artery. CONCLUSION: In patients with reperfused acute myocardial
infarction, the area of reduced FDG uptake correlates with the area at risk as
determined with the ESA method and is localized in the perfusion territory of the
culprit artery in the absence of necrosis, although the area of reduced FDG
uptake largely overestimates the size of the infarct and the ESA-based area at
risk.
PMID- 25848896
TI - Expression of surfactant protein D in airways of asthmatics and interleukin-13
modulation of surfactant protein D in human models of airway epithelium.
AB - BACKGROUND: Surfactant protein D (SP-D), a pattern recognition molecule, has been
shown to play roles in host defense such as opsonisation, aggregation of
pathogens, and modulation of the inflammatory response. In light of infection
induced exacerbations and damage to the airway epithelium from inflammation,
these functions of SP-D make it relevant in the development and pathogenesis of
asthma. METHODS: Expression of SP-D was examined in human airway sections and
primary airway epithelial cells (AEC) grown in air-liquid interface (ALI)
cultures and comparisons were made between those from asthmatic and non-asthmatic
donors. ALI cultures of AEC from non-asthmatic donors were examined for SP-D,
Mucin 5AC, and cytokeratin-5 expression at different stages of differentiation.
Interleukin-13 (IL-13) treatment of airway epithelium and its effect on SP-D
expression was studied using ALI and monolayer cultures of primary AEC from non
asthmatic and asthmatic donors. RESULTS: Airway epithelium of asthmatics,
compared to that of non-asthmatics, expressed increased levels of SP-D as
demonstrated in airway tissue sections (fraction of epithelium 0.66 +/- 0.026 vs.
0.50 +/- 0.043, p = 0.004) and ALI cultures (fraction of epithelium 0.50 +/- 0.08
vs. 0.25 +/- 0.07). SP-D expression decreased as ALI cultures differentiated from
7 days to 21 days (fraction of epithelium 0.62 +/- 0.04 to 0.23 +/- 0.03, p =
0.004). Treatment with IL-13 decreased SP-D expression in both ALI cultures
(fraction of epithelium 0.21 +/- 0.06 vs. 0.62 +/- 0.04, p = 0.0005) and
monolayer cultures (protein expression fold change 0.62 +/- 0.05) of non
asthmatic AEC; however, IL-13 had no significant effect on SP-D expression in
monolayer cultures of asthmatic AEC. Experiments with non-asthmatic monolayer
cultures indicate IL-13 exert its effect on SP-D through the IL-13 receptor
alpha1 and transcription factor STAT6. CONCLUSIONS: SP-D is expressed differently
in airways of asthmatics relative to that of non-asthmatics. This can have
implications on the increased susceptibility to infections and altered
inflammatory response in asthmatic patients. Future functional studies on the
role of SP-D in asthma can provide better insight into defects in the structure
and regulation of SP-D.
PMID- 25848899
TI - Reduced Radiation Dose with Model-based Iterative Reconstruction versus Standard
Dose with Adaptive Statistical Iterative Reconstruction in Abdominal CT for
Diagnosis of Acute Renal Colic.
AB - PURPOSE: To evaluate the accuracy of reduced-dose abdominal computed tomographic
(CT) imaging by using a new generation model-based iterative reconstruction
(MBIR) to diagnose acute renal colic compared with a standard-dose abdominal CT
with 50% adaptive statistical iterative reconstruction (ASIR). MATERIALS AND
METHODS: This institutional review board-approved prospective study included 118
patients with symptoms of acute renal colic who underwent the following two
successive CT examinations: standard-dose ASIR 50% and reduced-dose MBIR. Two
radiologists independently reviewed both CT examinations for presence or absence
of renal calculi, differential diagnoses, and associated abnormalities. The
imaging findings, radiation dose estimates, and image quality of the two CT
reconstruction methods were compared. Concordance was evaluated by kappa
coefficient, and descriptive statistics and t test were used for statistical
analysis. RESULTS: Intraobserver correlation was 100% for the diagnosis of renal
calculi (kappa = 1). Renal calculus (tau = 98.7%; kappa = 0.97) and obstructive
upper urinary tract disease (tau = 98.16%; kappa = 0.95) were detected, and
differential or alternative diagnosis was performed (tau = 98.87% kappa = 0.95).
MBIR allowed a dose reduction of 84% versus standard-dose ASIR 50% (mean volume
CT dose index, 1.7 mGy +/- 0.8 [standard deviation] vs 10.9 mGy +/- 4.6; mean
size-specific dose estimate, 2.2 mGy +/- 0.7 vs 13.7 mGy +/- 3.9; P < .001)
without a conspicuous deterioration in image quality (reduced-dose MBIR vs ASIR
50% mean scores, 3.83 +/- 0.49 vs 3.92 +/- 0.27, respectively; P = .32) or
increase in noise (reduced-dose MBIR vs ASIR 50% mean, respectively, 18.36 HU +/-
2.53 vs 17.40 HU +/- 3.42). Its main drawback remains the long time required for
reconstruction (mean, 40 minutes). CONCLUSION: A reduced-dose protocol with MBIR
allowed a dose reduction of 84% without increasing noise and without an
conspicuous deterioration in image quality in patients suspected of having renal
colic.
PMID- 25848900
TI - Prostate Cancer: The European Society of Urogenital Radiology Prostate Imaging
Reporting and Data System Criteria for Predicting Extraprostatic Extension by
Using 3-T Multiparametric MR Imaging.
AB - PURPOSE: To retrospectively assess the use of the European Society of Urogenital
Radiology (ESUR) Prostate Imaging Reporting and Data System (PI-RADS) criteria
and 3-T multiparametric magnetic resonance (MR) imaging for detection of
extraprostatic extension (EPE) of prostate cancer. MATERIALS AND METHODS: The
institutional review board approval requirement was waived. Consecutive patients
with prostate cancer (n = 133) underwent 3-T multiparametric MR imaging before
prostatectomy. Lesions were assessed by using ESUR/PI-RADS criteria for T2
weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging, and
by using the sum of these scores. Zonal dominant parameters corresponding to the
score of diffusion-weighted imaging for peripheral zone lesions and to T2
weighted imaging scores for transitional zone lesions were calculated. In
addition, the presence of EPE in each patient was evaluated on the basis of
subjective multiparametric MR imaging features. Histopathologic examination of
whole-mount radical prostatectomy specimens was used as the reference standard.
Sensitivity, specificity, positive predictive, and negative predictive values;
likelihood ratios; and areas under the receiver operating characteristic curve
were calculated for each parameter on the basis of its usefulness for prediction
of EPE. RESULTS: EPE was found in 60 of 133 (45%) patients. Receiver operating
characteristic curve analysis for the prediction of EPE revealed an area under
the curve of 0.72 for T2-weighted, 0.67 for diffusion-weighted, and 0.64 for
dynamic contrast-enhanced imaging; 0.74 for the dominant parameter; and 0.74 for
the sum of the PI-RADS scores, and a score of 5 was defined as the best threshold
for the individual parameters, with a score greater than or equal to 13 as the
threshold for the sum of the PI-RADS scores. By applying these thresholds,
sensitivity, negative predictive value, and negative likelihood ratio (ruling out
EPE) were 77%, 77%, and 0.36, respectively, and specificity, positive predictive
value, and positive likelihood ratio (ruling in EPE) were 64%, 64%, and 2.15,
respectively, for the dominant parameter. Feature analysis showed an area under
the curve of 0.72; sensitivity, negative predictive value, and negative
likelihood ratio of 63%, 72%, and 0.56, respectively, and specificity, positive
predictive value, and positive likelihood ratio of 78%, 70%, and 3.77,
respectively. CONCLUSION: ESUR/PI-RADS criteria showed moderate overall accuracy
for use in the prediction of EPE, and these results were similar to those of
multiparametric MR imaging assessment of features in this study sample.
PMID- 25848901
TI - Disrupted Functional Brain Connectome in Patients with Posttraumatic Stress
Disorder.
AB - PURPOSE: To use resting-state functional magnetic resonance (MR) imaging and
graph theory approaches to systematically investigate the topological
organization of the functional connectome of patients with posttraumatic stress
disorder (PTSD). MATERIALS AND METHODS: This study was approved by the research
ethics committee, and all subjects provided informed consent for participation.
Seventy-six patients with PTSD caused by an earthquake and 76 control subjects
who experienced the same disaster were matched for age, sex, and years of
education. The study subjects underwent resting-state functional MR imaging. The
whole-brain functional network was then constructed by thresholding partial
correlation matrices of 90 brain regions. The topological organization of the
constructed network was analyzed by using graph theory approaches. Nonparametric
permutation tests were also used for group comparisons of topological metrics.
RESULTS: Compared with the control subjects, patients with PTSD exhibited
abnormalities in global properties, including a significant decrease in path
length (P = .0002) and increases in the clustering coefficient (P = .0014),
global efficiency (P = .0002), and local efficiency (P = .0004). Locally, the
patients with PTSD exhibited increased centrality in nodes that are predominately
involved in the default-mode network (DMN) and the salience network (SN),
including the posterior cingulate gyrus, the precuneus, the insula, the putamen,
the pallidum, and the temporal regions. CONCLUSION: These results suggest that
individuals with PTSD exhibit a shift toward "small-worldization" (in which the
network transforms from a random or regular network to a small-world network)
rather than toward randomization; furthermore, the disequilibrium between the DMN
and the SN might be associated with the pathophysiology of PTSD.
PMID- 25848902
TI - Chronic Obstructive Pulmonary Disease: Pulmonary Function and CT Lung Attenuation
Do Not Show Linear Correlation.
AB - PURPOSE: To determine whether the relationship between pulmonary function and
computed tomographic (CT) lung attenuation in chronic obstructive pulmonary
disease (COPD), which is traditionally described with single univariate and
multivariate statistical models, could be more accurately described with a
multiple model estimation approach. MATERIALS AND METHODS: The study was approved
by the local ethics committee. All participants provided written informed
consent. The prediction of the percentage area with CT attenuation values less
than -950 HU at inspiration (%LAA-950insp) and less than -910 HU at expiration
(%LAA-910exp) obtained with single univariate and multivariate models was
compared with that obtained with a multiple model estimation approach in 132
patients with COPD. RESULTS: At univariate analysis, %LAA-950insp and %LAA-910exp
values higher than the mean value of this cohort (19.1% and 22.0%) showed better
correlation with percentage of predicted diffusing capacity of lung for carbon
monoxide (Dlco%) than with airflow obstruction (forced expiratory volume in 1
second [FEV1]/vital capacity [VC]). Conversely, %LAA-950insp and %LAA-910exp
values lower than the mean value were correlated with FEV1/VC but not with Dlco%.
Multiple model estimation performed with two multivariate regressions, each
selecting the most appropriate functional variables (FEV1/VC for mild parenchymal
destruction, Dlco% and functional residual capacity for severe parenchymal
destruction), predicted better than single multivariate regression both %LAA
950insp (R(2) = 0.75 vs 0.46) and %LAA-910exp (R(2) = 0.83 vs 0.63). CONCLUSION:
The relationship between pulmonary function data and CT densitometric changes in
COPD varies with the level of lung attenuation impairment. The nonlinear profile
of this relationship is accurately predicted with a multiple model estimation
approach.
PMID- 25848903
TI - Determination of Single-Kidney Glomerular Filtration Rate in Human Subjects by
Using CT.
AB - PURPOSE: To test the hypothesis that computed tomography (CT)-derived
measurements of single-kidney glomerular filtration rate (GFR) obtained in human
subjects with 64-section CT agree with those obtained with iothalamate clearance,
a rigorous reference standard. MATERIALS AND METHODS: The institutional review
board approved this HIPAA-compliant study, and written informed consent was
obtained. Ninety-six patients (age range, 51-73 years; 46 men, 50 women) with
essential (n = 56) or renovascular (n = 40) hypertension were prospectively
studied in controlled conditions (involving sodium intake and renin-angiotensin
blockade). Single-kidney perfusion, volume, and GFR were measured by using
multidetector CT time-attenuation curves and were compared with GFR measured by
using iothalamate clearance, as assigned to the right and left kidney according
to relative volumes. The reproducibility of CT GFR over a 3-month period (n = 21)
was assessed in patients with renal artery stenosis who were undergoing stable
medical treatment. Statistical analysis included the t test, Wilcoxon signed rank
test, linear regression, and Bland-Altman analysis. RESULTS: CT GFR values were
similar to those of iothalamate clearance (mean +/- standard deviation, 38.2
mL/min +/- 18 vs 41.6 mL/min +/- 17; P = .062). Stenotic kidney CT GFR in
patients with renal artery stenosis was lower than contralateral kidney GFR or
essential hypertension single-kidney GFR (mean, 23.1 mL/min +/- 13 vs 36.9 mL/min
+/- 17 [P = .0008] and 45.2 mL/min +/- 16 [P = .019], respectively), as was
iothalamate clearance (mean, 26.9 mL/min +/- 14 vs 38.5 mL/min +/- 15 [P = .0004]
and 49.0 mL/min +/- 14 [P = .001], respectively). CT GFR correlated well with
iothalamate GFR (linear regression, CT GFR = 0.88*iothalamate GFR, r(2) = 0.89, P
< .0001), and Bland-Altman analysis was used to confirm the agreement. CT GFR was
also moderately reproducible in medically treated patients with renal artery
stenosis (concordance coefficient correlation, 0.835) but was unaffected by
revascularization (mean, 25.3 mL/min +/- 15.2 vs 30.3 mL/min +/- 18.5; P = .097).
CONCLUSION: CT assessments of single-kidney GFR are reproducible and agree well
with a reference standard. CT can be useful to obtain minimally invasive
estimates of bilateral single-kidney function in human subjects.
PMID- 25848904
TI - Thyroid Nodules: Nondiagnostic Cytologic Results according to Thyroid Imaging
Reporting and Data System before and after Application of the Bethesda System.
AB - PURPOSE: To compare the malignancy rates and the effectiveness of the Thyroid
Imaging Reporting and Data System (TIRADS) for risk stratification of nodules
with nondiagnostic results classified before and after application of the
Bethesda System for Reporting Thyroid Cytopathology. MATERIALS AND METHODS: This
retrospective study was approved by an institutional review board, with waiver of
informed consent. A total of 763 patients with 790 thyroid nodules and
nondiagnostic cytologic results were included (mean age +/- standard deviation,
52.3 years +/- 11.5), 485 nodules from the pre-Bethesda period (from March 2007
to December 2008) and 305 nodules from the post-Bethesda period (from May 2011 to
May 2012). A TIRADS category was assigned to each thyroid nodule on the basis of
the number of features that appeared suspicious for cancer at ultrasonography
(US). Malignancy rates and TIRADS categories during the two periods were
compared. Correlation between TIRADS category and malignancy risk between the two
periods was evaluated and compared. RESULTS: The malignancy rates of nodules with
nondiagnostic cytologic results were not significantly different between the two
periods (P = .148). Malignancy risk of TIRADS category 3, 4a, 4b, 4c, and 5 was
1.8%, 5.7%, 4.1%, 29.8%, and 16.7%, for the pre-Bethesda period, and 1.6%, 3.0%,
7.1%, 16.3%, and 25.0% for the post-Bethesda period, respectively. Near-perfect
correlation was seen between the TIRADS category and malignancy risk in the post
Bethesda period (r = 0.961, P = .009), while no significant correlation was found
in the pre-Bethesda period (r = 0.731, P = .161). CONCLUSION: Malignancy risk
stratification with TIRADS was more effective for nodules with nondiagnostic
cytologic results classified according to the Bethesda System. When these
Bethesda-classified nodules with nondiagnostic results are evaluated as TIRADS
category 3 or 4a, they may be treated conservatively with follow-up US, but when
other cytologic classifications are applied, follow-up US and fine- needle
aspiration must be considered for nodules showing one or more features suspicious
for cancer at US.
PMID- 25848905
TI - Gadolinium retention in the dentate nucleus and globus pallidus is dependent on
the class of contrast agent.
AB - PURPOSE: To compare changes in signal intensity (SI) ratios of the dentate
nucleus (DN) and the globus pallidus (GP) to those of other structures on
unenhanced T1-weighted magnetic resonance (MR) images between linear and
macrocyclic gadolinium-based contrast agents (GBCAs). MATERIALS AND METHODS: The
study was approved by the ethical committee of the University of Heidelberg
(reference no. S-324/2014). Owing to the retrospective character of the study,
the ethical committee did not require any written informed consent. Two groups of
50 patients who underwent at least six consecutive MR imaging examinations with
the exclusive use of either a linear GBCA (gadopentetate dimeglumine) or a
macrocyclic GBCA (gadoterate meglumine) were analyzed retrospectively. The
difference in mean SI ratios of DN to pons and GP to thalamus on unenhanced T1
weighted images from the last and first examinations was calculated. One-sample
and independent-sample t tests were used to assess the difference in SI ratios
for both groups, and regression analysis was performed to account for potential
confounders. RESULTS: The SI ratio difference in the linear group was greater
than 0 (mean DN difference +/- standard deviation, 0.0407 +/- 0.0398 [P < .001];
GP, 0.0287 +/- 0.0275 [P < .001]) and significantly larger (DN, P < .001 and
standardized difference of 1.16; GP, P < .001 and standardized difference of
0.81) than that in the macrocyclic group, which did not differ from 0 (DN, 0.0016
+/- 0.0266 [P = .680]; GP, 0.0031 +/- 0.0354 [P = .538]). The SI ratio difference
between the last and first examinations for the DN remained significantly
different between the two groups in the regression analysis (P < .001).
CONCLUSION: This study indicates that an SI increase in the DN and GP on T1
weighted images is caused by serial application of the linear GBCA gadopentetate
dimeglumine but not by the macrocyclic GBCA gadoterate meglumine. Clinical
implications of this observation remain unclear.
PMID- 25848907
TI - Histopathological Analysis of Internal Limiting Membrane Surgically Peeled From
Eyes with Epiretinal Membrane.
AB - PURPOSE: To investigate histopathological changes of internal limiting membrane
(ILM) in patients with epiretinal membrane (ERM) Materials and Methods: Forty-two
eyes of 42 patients who were diagnosed as ERM and enrolled for vitreoretinal
surgery were included in this study. Brilliant Blue G (BBG) was used to stain the
ILM in all patients. ILM was peeled in all subjects and analyzed by light
microscopy (methylene blue-Azur II * 40). ILM samples were then fixed in 2.5%
glutaraldehyde solution and examined in JEOL-JEM 1400 and 2100F electron
microscope and photographed by CCD camera (Gatan Inc., Pleasanton, CA). RESULTS:
Remained ERM fragments were observed on 80% of ILM's. Vacuolization of ILM was
observed in a patient with diabetic ERM. There were cells and cellular fragments
observed mostly at retinal side of ILM which was likely to be a fragment of
Muller cells of retina. CONCLUSIONS: Most of the ILM's had residual ERM tissue
and contained cells and cellular fragments at retinal side of ILM's. ILM peeling
might have a role in decreasing ERM recurrence by removal of residual ERM
tissues.
PMID- 25848906
TI - Pleiotropic functions of the tumor- and metastasis-suppressing matrix
metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice.
AB - INTRODUCTION: Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an
important regulator of innate immunity that has oncosuppressive actions in
numerous tumor types. METHODS: We have intercrossed Mmp8-null mice with the
Polyoma virus middle T oncogene-driven (MMTV-PyMT) mouse model of mammary cancer
to explore the effects of loss of MMP-8 on the incidence and progression of
mammary carcinomas. RESULTS: In this aggressive mouse model of breast cancer,
loss of MMP-8 accelerated tumor onset even further, such that 90% of MMTV-PyMT;
Mmp8-null female mice were tumor-bearing at the time of weaning. Throughout the
14 weeks of the model, tumor burden increased in homozygous Mmp8-null mice
compared to Mmp8-wild-type and -heterozygote animals. Likewise, lung metastasis
dramatically increased in the MMTV-PyMT; Mmp8-null mice. Immunohistochemistry
revealed that tumors in wild-type, Mmp8-heterozygotes and -null animals had
similar vascular density at 8 weeks, but at 10 weeks Mmp8-wild-type tumors had a
lower vascularity than their heterozygote and null counterparts. No differences
in macrophage infiltration were apparent throughout primary tumor development,
though at 10 weeks a drop in neutrophil infiltrates was observed in Mmp8-wild
type tumors. Using quantitative real-time RT-PCR, we tracked the expression of
the entire Mmp and Timp gene families, observing a significant decrease in Mmp3
expression in Mmp8-null tumors compared to wild-type and heterozygotes throughout
the time course of the model, which was confirmed at the protein level.
CONCLUSIONS: These findings provide novel insight into the suppressive action of
MMP-8 on mammary tumorigenesis and metastasis, and indicate that the loss of MMP
8 likely has pleiotropic effects on innate immunity and angiogenesis that are
reflected in changes in the protease web.
PMID- 25848908
TI - Bacteremia in adult cancer patients with apparently stable febrile neutropenia:
data from a cohort of 692 consecutive episodes from a single institution.
AB - BACKGROUND: Bacteremia is associated with increased risk of complications in
patients with febrile neutropenia (FN), although few clinical studies have
reported outcomes in apparently stable patients (ASPs) who could be candidates
for home treatment. OBJECTIVE: To assess the risk factors and the impact of
bacteremia in ASPs. METHODS: We retrospectively analyzed 861 consecutive episodes
of FN that were classifed according to their presentation into 2 categories:
clearly unstable patients and ASPs. We estimated the incidence of bacteremia and
severe complications in ASPs. We analyzed predictors for bacteremia and the
discriminatory ability of the MASCC score in this setting. RESULTS: We classifed
692 episodes as ASPs. Bacteremia occurred in 6%, major complications were noted
in 7.3%, and death occurred in 1.3%. Patients with bacteremia had more
complications (odds ratio [OR], 8.2), and mortality (OR, 8.2). The integration of
the MASCC score and bacteremic status predicted complications with an area under
the receiver operating characteristic (ROC) curve of 0.74, sensitivity of 36%,
and specifcity of 94%. Predictors of bacteremia were temperature >= 39 degrees
C/102.2 degrees F (OR, 3), rigors (OR, 2.2), ECOG PS >= 2 (OR, 2.1), and advanced
cancer (OR, 2.5). Two percent of patients who remained afebrile for 48 hours had
positive blood cultures afterward. LIMITATIONS: A single-center, retrospective
analysis, and the absence of a validation set to test the model's discriminatory
ability. CONCLUSIONS: Bacteremia is infrequent among ASPs but is associated with
a high risk of complications. We identifed several variables that could improve
the prognostic classifcation of clinically stable FN.
PMID- 25848909
TI - Treatment patterns and clinical effectiveness in metastatic castrate resistant
prostate cancer after first-line docetaxel.
AB - BACKGROUND: Treatment for metastatic castrate-resistant prostate cancer in
community settings is not well understood. OBJECTIVE: To examine treatment
patterns, sequencing, and outcomes in patients receiving second- and third-line
treatment after first-line docetaxel. METHODS: We used a community oncology
database to identify patients who progressed after line 1 docetaxel (D) and
received line 2 cabazitaxel (DC), abiraterone (DA), or other therapy (DO).
Progression-free survival (PFS) and overall survival (OS) were assessed using
Kaplan- Meier and Cox regression models. Line 3 included subsets DCA and DAC.
RESULTS: Line 2 groups (DC = 60 patients, DA = 71, DO = 153) did not differ
significantly on demographic and clinical characteristics or median PFS on
docetaxel therapy. Cox regression for OS by line 2 groups showed increased risk
for DA compared with DC (HR, 1.69; P = .026) when 24 untreated DO patients were
excluded. A similar nonsignificant pattern was observed when the 24 untreated
patients were included. Of patients receiving DC in line 2, a nominally greater
proportion received A in line 3 (57%, 34 of 60 patients) than did patients who
received DA in line 2 followed by C in line 3 (25%, 18 of 71). LIMITATIONS: There
was a small sample for line 3, and unexamined confounds and selection biases in
observational research. Conclusions Treatment patterns in community settings
following docetaxel are complex and may involve multiple hormonal agents prior to
disease progression. Cabazitaxel may not be optimally used in advanced disease.
Although Cox regression showed increased risk of death for DA compared with DC,
results need to be validated prospectively. CONCLUSIONS: Treatment patterns in
community settings following docetaxel are complex and may involve multiple
hormonal agents prior to disease progression. Cabazitaxel may not be optimally
used in advanced disease. Although Cox regression showed increased risk of death
for DA compared with DC, results need to be validated prospectively.
PMID- 25848910
TI - Metastic melanoma masquerading as disseminated sporotrichosis.
AB - A 66-year-old man presented with diffuse slate-gray skin discoloration and
multiorgan failure. Diagnostic workup showed disseminated bone and visceral
lesions and positive Sporothrix serology. He was treated with antifungals for
disseminated sporotrichosis but he died shortly after. Autopsy revealed
metastatic melanoma with diffuse melanosis and no Sporothrix infection.
PMID- 25848911
TI - Atomically mixed Fe-group nanoalloys: catalyst design for the selective
electrooxidation of ethylene glycol to oxalic acid.
AB - We demonstrate electric power generation via the electrooxidation of ethylene
glycol (EG) on a series of Fe-group nanoalloy (NA) catalysts in alkaline media. A
series of Fe-group binary NA catalysts supported on carbon (FeCo/C, FeNi/C, and
CoNi/C) and monometallic analogues (Fe/C, Co/C, and Ni/C) were synthesized.
Catalytic activities and product distributions on the prepared Fe-group NA
catalysts in the EG electrooxidation were investigated by cyclic voltammetry and
chronoamperometry, and compared with those of the previously reported FeCoNi/C,
which clarified the contributory factors of the metal components for the EG
electrooxidation activity, C2 product selectivity, and catalyst durability. The
Co-containing catalysts, such as Co/C, FeCo/C, and FeCoNi/C, exhibit relatively
high catalytic activities for EG electrooxidation, whereas the catalytic
performances of Ni-containing catalysts are relatively low. However, we found
that the inclusion of Ni is a requisite for the prevention of rapid degradation
due to surface modification of the catalyst. Notably, FeCoNi/C shows the highest
selectivity for oxalic acid production without CO2 generation at 0.4 V vs. the
reversible hydrogen electrode (RHE), resulting from the synergetic contribution
of all of the component elements. Finally, we performed power generation using
the direct EG alkaline fuel cell in the presence of the Fe-group catalysts. The
power density obtained on each catalyst directly reflected the catalytic
performances elucidated in the electrochemical experiments for the corresponding
catalyst. The catalytic roles and alloying effects disclosed herein provide
information on the design of highly efficient electrocatalysts containing Fe
group metals.
PMID- 25848913
TI - Markers for the identification of late breast cancer recurrence.
AB - Postmenopausal women with early breast cancer are at an ongoing risk of relapse,
even after successful surgery and treatment of the primary tumor. The treatment
of breast cancer has changed in the past few years because of the discovery of
prognostic and predictive biomarkers that allow individualized breast cancer
treatment. However, it is still not clear how to identify women that are at high
risk of a late recurrence. Clinical parameters are good prognostic markers for
early recurrence, but only nodal status and, to a lesser extent, tumor size have
proven to be strong prognostic markers for late recurrence. Multi-gene signatures
have become widely used for the prediction of overall recurrence risk and
tailoring administration of adjuvant chemotherapy, but only a few have been shown
to be prognostic for late (distant) relapse. There is a need to accurately
identify women who may benefit from extended endocrine therapy but also those who
may be spared any additional treatment. Recent results from large clinical trials
have shown that the research is going in the right direction, and these results
might help to optimize extended endocrine therapy for patients with early breast
cancer. However, further research is needed to select individual biomarkers or
multi-gene signatures that offer identification of late recurrence specifically
and thus justify routine use of these tests in the clinical setting.
PMID- 25848914
TI - Localization and functional characterization of the extrinsic subunits of
photosystem II: an update.
AB - Photosystem II (PSII), which catalyzes photosynthetic water oxidation, is
composed of more than 20 subunits, including membrane-intrinsic and -extrinsic
proteins. The extrinsic proteins of PSII shield the catalytic Mn4CaO5 cluster
from exogenous reductants and serve to optimize oxygen evolution at physiological
ionic conditions. These proteins include PsbO, found in all oxygenic organisms,
PsbP and PsbQ, specific to higher plants and green algae, and PsbU, PsbV, CyanoQ,
and CyanoP in cyanobacteria. Furthermore, red algal PSII has PsbQ' in addition to
PsbO, PsbV, and PsbU, and diatoms have Psb31 in supplement to red algal-type
extrinsic proteins, exemplifying the functional divergence of these proteins
during evolution. This review provides an updated summary of recent findings on
PSII extrinsic proteins and discusses their binding, function, and evolution
within various photosynthetic organisms.
PMID- 25848912
TI - Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of
metalloproteinase-1 are associated with vascular complications in patients with
type 1 diabetes: the EURODIAB Prospective Complications Study.
AB - BACKGROUND: Impaired regulation of extracellular matrix remodeling by matrix
metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may
contribute to vascular complications in patients with type 1 diabetes. We
investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and
cardiovascular disease (CVD) or microvascular complications in type 1 diabetic
patients. We also evaluated to which extent these associations could be explained
by low-grade inflammation (LGI) or endothelial dysfunction (ED). METHODS: 493
type 1 diabetes patients (39.5 +/- 9.9 years old, 51% men) from the EURODIAB
Prospective Complications Study were included. Linear regression analysis was
applied to investigate differences in plasma levels of MMP-1, -2, -3, -9, -10,
and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All
analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally
for other cardiovascular risk factors including LGI and ED. RESULTS: Patients
with CVD (n = 118) showed significantly higher levels of TIMP-1 [beta = 0.32 SD
(95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375).
Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with
higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001,
respectively). Severity of retinopathy was significantly associated with higher
levels of MMP-2 (p-trend = 0.017). These associations remained significant after
further adjustment for markers of LGI and ED. CONCLUSIONS: These data support the
hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3
and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in
type 1 diabetes.
PMID- 25848916
TI - Accumulation of Metals and Boron in Phragmites australis Planted in Constructed
Wetlands Polishing Real Electroplating Wastewater.
AB - The concentration of metals (Al, Cu, Fe, Mn, Ni, Zn) and B were determined in the
above- and belowground biomass of Phragmites australis collected from the
microcosm constructed wetland system used for the polishing of real
electroplating wastewater. Translocation factor and bioconcentration factor were
determined. Pearson correlation test was used to determine correlation between
metal concentration in substrate and above- and belowground parts of Phragmites
australis. The obtained results suggested that Phragmites australis did not play
a major role as an accumulator of metals. It was observed also that the substrate
could have exerted an effect on the translocation of Ni, Cu, Zn and Mn. The
analysed concentrations of metals and B in biomass were in the range or even
below the concentrations reported in the literature with the exception of Ni. The
aboveground biomass was found suitable as a composting input in terms of metals
concentrations.
PMID- 25848915
TI - Combined histone deacetylase inhibition and tamoxifen induces apoptosis in
tamoxifen-resistant breast cancer models, by reversing Bcl-2 overexpression.
AB - INTRODUCTION: The emergence of hormone therapy resistance, despite continued
expression of the estrogen receptor (ER), is a major challenge to curing breast
cancer. Recent clinical studies suggest that epigenetic modulation by histone
deacetylase (HDAC) inhibitors reverses hormone therapy resistance. However,
little is known about epigenetic modulation of the ER during acquired hormone
resistance. Our recent phase II study demonstrated that HDAC inhibitors re
sensitize hormone therapy-resistant tumors to the anti-estrogen tamoxifen. In
this study, we sought to understand the mechanism behind the efficacy of this
combination. METHODS: We generated cell lines resistant to tamoxifen, named TAMRM
and TAMRT, by continuous exposure of ER-positive MCF7 and T47D cells,
respectively to 4-hydroxy tamoxifen for over 12 months. HDAC inhibition, along
with pharmacological and genetic manipulation of key survival pathways, including
ER and Bcl-2, were used to characterize these resistant models. RESULTS: The
TAMRM cells displayed decreased sensitivity to tamoxifen, fulvestrant and
estrogen deprivation. Consistent with previous models, ER expression was retained
and the gene harbored no mutations. Compared to parental MCF7 cells, ER
expression in TAMRM was elevated, while progesterone receptor (PGR) was lost.
Sensitivity of ER to ligands was greatly reduced and classic ER response genes
were suppressed. This model conveyed tamoxifen resistance through transcriptional
upregulation of Bcl-2 and c-Myc, and downregulation of the cell cycle checkpoint
protein p21, manifesting in accelerated growth and reduced cell death. Similar to
TAMRM cells, the TAMRT cell line exhibited substantially decreased tamoxifen
sensitivity, increased ER and Bcl-2 expression and significantly reduced PGR
expression. Treatment with HDAC inhibitors reversed the altered transcriptional
events and reestablished the sensitivity of the ER to tamoxifen resulting in
substantial Bcl-2 downregulation, growth arrest and apoptosis. Selective
inhibition of Bcl-2 mirrored these effects in presence of an HDAC inhibitor.
CONCLUSIONS: Our model implicates elevated ER and Bcl-2 as key drivers of anti
estrogen resistance, which can be reversed by epigenetic modulation through HDAC
inhibition.
PMID- 25848917
TI - Detection of survival motor neuron protein in buccal cells through
electrochemiluminescence-based assay.
AB - Spinal muscular atrophy (SMA) is a severe autosomal recessive disorder affecting
one in every 10,000 live births. The disease is characterized by loss of alpha
motor neurons in the spinal cord that leads to progressive atrophy and weakness
of limb and trunk muscles. This neuromuscular disorder results from deletions
and/or mutations within the survival motor neuron 1 (SMN1) gene, leading to a
pathologically decreased expression of functional full-length SMN protein. Here
we report on the investigation to measure SMN protein levels through
electrochemiluminescence immunoassay (ECLIA). This simple assay is a highly
quantitative method able to measure SMN protein levels in human, mouse, and rat
samples throughout a wide working range with low intra- and interassay error. The
sensitivity for human SMN is 30 pg/mL and provides a new tool for the set up of
high-throughput screening for basic research. Moreover, we describe a novel tool
for a noninvasive assessment of SMN in buccal cells derived from healthy donors,
SMA carriers, and SMA patients. The availability of a validated quantitative
ECLIA should improve the investigation of novel compounds for the treatment of
SMA.
PMID- 25848919
TI - Controlling the fluorescence behavior of 1-pyrenesulfonate by cointercalation
with a surfactant in a layered double hydroxide.
AB - Zn-Al layered double hydroxides (LDHs) containing solely 1-pyrenesulfonate (PS)
or 1-heptanesulfonate (HS) anions, or a mixture of the two with HS/PS molar
ratios ranging between ca. 7.5 and 82, were prepared by the direct synthesis
method and characterized by powder X-ray diffraction, thermal and elemental
analyses, scanning electron microscopy, and FT-IR, FT-Raman, and (13)C{(1)H} CP
MAS NMR spectroscopies. Well-ordered intercalates were obtained with basal
spacings of 18.8 A for the LDH intercalated by PS and 19.2-19.4 A for the other
materials containing HS. The photophysics of the solids, as well as the PS probe
dissolved in water and common organic solvents (aiming to compare the behavior of
the "isolated" molecule with that in the solid), were investigated by steady
state and time-resolved fluorescence techniques. The fluorescence spectra of the
solid samples display two bands with maxima at 376 and 495 nm. Depending on the
HS/PS ratios, the band intensity ratio (obtained at 375 and 520 nm) changes,
reflecting different contributions from monomer and dimer species. The decays
collected at 375 nm are biexponentials with a major component (~97% of the total
fluorescence) of 105 ns for the highest HS/PS ratio, which further loses
importance with an increase in the PS content. When the decays are collected at
480 and 520 nm, the fits are triexponentials with a major component varying from
108 to 124 ns, attributed to an excimer. Steady-state and time-resolved
measurements with PS in solution (ethanol, methanol, DMF, DMSO, and water) were
also measured, and a comparison of the vibronic I1/I3 ratio and lifetimes in
water (65 ns) with those in the LDHs indicates that the PS probe in the
cointercalated LDHs is surrounded by the HS surfactant.
PMID- 25848918
TI - Nitroxoline impairs tumor progression in vitro and in vivo by regulating
cathepsin B activity.
AB - Cathepsin B is a ubiquitously expressed lysosomal cysteine protease that
participates in protein turnover within lysosomes. However, its protein and
activity levels have been shown to be increased in cancer. Cathepsin B
endopeptidase activity is involved in the degradation of extracellular matrix, a
process that promotes tumor invasion, metastasis and angiogenesis. Previously, we
reported an established antibiotic nitroxoline as a potent and selective
inhibitor of cathepsin B. In the present study, we elucidated its anti-tumor
properties in in vitro and in vivo tumor models. Tumor and endothelial cell lines
with high levels of active cathepsin B were selected for functional analysis of
nitroxoline in vitro. Nitroxoline significantly reduced extracellular DQ-collagen
IV degradation by all evaluated cancer cell lines using spectrofluorimetry.
Nitroxoline also markedly decreased tumor cell invasion monitored in real time
and reduced the invasive growth of multicellular tumor spheroids, used as a 3D in
vitro model of tumor invasion. Additionally, endothelial tube formation was
significantly reduced by nitroxoline in an in vitro angiogenesis assay. Finally,
nitroxoline significantly abrogated tumor growth, angiogenesis and metastasis in
vivo in LPB fibrosarcoma and MMTV-PyMT breast cancer mouse models. Overall, our
results designate nitroxoline as a promising drug candidate for anti-cancer
treatment.
PMID- 25848920
TI - Sandwich-structured nanohybrid paper based on controllable growth of
nanostructured MnO2 on ionic liquid functionalized graphene paper as a flexible
supercapacitor electrode.
AB - A sandwich-structured flexible supercapacitor electrode has been developed based
on MnO2 nanonest (MNN) modified ionic liquid (IL) functionalized graphene paper
(GP), which is fabricated by functionalizing graphene nanosheets with an amine
terminated IL (i.e., 1-(3-aminopropyl)-3-methylimidazolium bromide) to form
freestanding IL functionalized GP (IL-GP), and then modifying IL-GP with a unique
MNN structure via controllable template-free ultrasonic electrodeposition. The as
obtained MNN modified IL-GP (MNN/IL-GP) inherits the excellent pseudocapacity of
the metal oxide, the high conductivity and electric double layer
charging/discharging of IL-graphene composites, and therefore shows an enhanced
supercapacitor performance. The maximum specific capacitance of 411 F g(-1) can
be achieved by chronopotentiometry at a current density of 1 A g(-1). Meanwhile,
the MNN/IL-GP electrode exhibits excellent rate capability and cycling stability,
its specific capacitance is maintained at 70% as the current densities increase
from 1 to 20 A g(-1) and 85% at a current density of 10 A g(-1) after 10 000
cycles. More importantly, the MNN/IL-GP displays distinguished mechanical
stability and flexibility for device packaging, although its thickness is merely
8 MUm. These features collectively demonstrate the potential of MNN/IL-GP as a
high-performance paper electrode for flexible and lightweight and highly
efficient electrochemical capacitor applications.
PMID- 25848921
TI - Motor neuron disease: loss-of-function mutations in TBK1 can cause familial ALS.
PMID- 25848922
TI - Stroke: more than meets the eye--big consequences of small strokes.
AB - A long-term outcome analysis in patients with lacunar stroke enrolled in the
Secondary Prevention of Small Subcortical Strokes trial highlights the relevance
of functional disability after small-vessel strokes. These data support the
emerging 'burden of disease' concept in individuals with cerebral
microangiopathy, and the role of MRI in outcome prediction.
PMID- 25848924
TI - Using a Treat-to-Target Management Strategy to Improve the Doctor-Patient
Relationship in Inflammatory Bowel Disease.
AB - The doctor-patient relationship (DPR) in inflammatory bowel disease (IBD) has
been facing new challenges, in part due to the substantial progress in medical
and surgical management and also due to the rapid expansion of patient access to
medical information. Not surprisingly, the complexity of IBD care and
heterogeneity of the disease types may lead to conflict between a physician's
therapeutic recommendations and the patient's wishes. In this commentary, we
propose that the so-called "treat-to-target" approach of objective targets of
disease control and serial adjustments to therapies can also strengthen the DPR
in IBD by enabling defined trials of alternative approaches, followed by a more
objective assessment and reconsideration of treatments. We contend that such
respect for patient autonomy and the use of objective markers of disease activity
improves the DPR by fostering trust and both engaging and empowering patients and
physicians with the information necessary to make shared decisions about
therapies.
PMID- 25848923
TI - Stimulation mapping of white matter tracts to study brain functional
connectivity.
AB - Despite advances in the new science of connectomics, which aims to
comprehensively map neural connections at both structural and functional levels,
techniques to directly study the function of white matter tracts in vivo in
humans have proved elusive. Direct electrical stimulation (DES) mapping of the
subcortical fibres offers a unique opportunity to investigate the functional
connectivity of the brain. This original method permits real-time anatomo
functional correlations, especially with regard to neural pathways, in awake
patients undergoing brain surgery. In this article, the goal is to review new
insights, gained from axonal DES, into the functional connectivity underlying the
sensorimotor, visuospatial, language and sociocognitive systems. Interactions
between these neural networks and multimodal systems, such as working memory,
attention, executive functions and consciousness, can also be investigated by
axonal stimulation. In this networking model of conation and cognition, brain
processing is not conceived as the sum of several subfunctions, but results from
the integration and potentiation of parallel-though partially overlapping
subnetworks. This hodotopical account, supported by axonal DES, improves our
understanding of neuroplasticity and its limitations. The clinical implications
of this paradigmatic shift from localizationism to hodotopy, in the context of
brain surgery, neurology, neurorehabilitation and psychiatry, are discussed.
PMID- 25848925
TI - The economic impact of Clostridium difficile infection: a systematic review.
AB - OBJECTIVES: With Clostridium difficile infection (CDI) on the rise, knowledge of
the current economic burden of CDI can inform decisions on interventions related
to CDI. We systematically reviewed CDI cost-of-illness (COI) studies. METHODS: We
performed literature searches in six databases: MEDLINE, Embase, the Health
Technology Assessment Database, the National Health Service Economic Evaluation
Database, the Cost-Effectiveness Analysis Registry, and EconLit. We also searched
gray literature and conducted reference list searches. Two reviewers screened
articles independently. One reviewer abstracted data and assessed quality using a
modified guideline for economic evaluations. The second reviewer validated the
abstraction and assessment. RESULTS: We identified 45 COI studies between 1988
and June 2014. Most (84%) of the studies were from the United States, calculating
costs of hospital stays (87%), and focusing on direct costs (100%). Attributable
mean CDI costs ranged from $8,911 to $30,049 for hospitalized patients. Few
studies stated resource quantification methods (0%), an epidemiological approach
(0%), or a justified study perspective (16%) in their cost analyses. In addition,
few studies conducted sensitivity analyses (7%). CONCLUSIONS: Forty-five COI
studies quantified and confirmed the economic impact of CDI. Costing methods
across studies were heterogeneous. Future studies should follow standard COI
methodology, expand study perspectives (e.g., patient), and explore populations
least studied (e.g., community-acquired CDI).
PMID- 25848926
TI - Local recurrence after endoscopic resection for large colorectal neoplasia: a
multicenter prospective study in Japan.
AB - OBJECTIVES: Conventional endoscopic resection (CER) is a widely accepted
treatment for early colorectal neoplasia; however, large colorectal neoplasias
remain problematic, as they necessitate piecemeal resection, increasing the risk
of local recurrence. Endoscopic submucosal dissection (ESD) can improve the en
bloc resection rate. This study aimed to evaluate local recurrence and its
associated risk factors after endoscopic resection (ER) for colorectal neoplasias
>=20 mm. METHODS: A multicenter prospective study at 18 medium- and high-volume
specialized institutions was conducted in Japan. Follow-up colonoscopy was
performed after 12 months in cases of complete resection and after 3-6 months in
cases of incomplete resection. Local recurrence was confirmed by endoscopic
findings and/or pathological analysis. RESULTS: Follow-up colonoscopy was
performed in 1,524 of 1,845 enrolled colorectal neoplasias (mean age, 65 years;
885 men; median tumor size, 32.8 mm). The local recurrence rates were 4.3%
(65/1,524), 6.8% (55/808), and 1.4% (10/716) for the entire cohort, for CER, and
for ESD, respectively. The relative risks of local recurrence were 0.21 (95%
confidence interval, 0.11-0.39) with ESD compared with CER, 0.32 (95% confidence
interval, 0.11-0.92) with en bloc ESD compared with en bloc CER, and 0.90 (95%
confidence interval, 0.39-2.12) with piecemeal ESD compared with piecemeal CER.
Significant factors associated with local recurrence were piecemeal resection,
laterally spreading tumors of granular type, tumor size >=40 mm, no pre-treatment
magnification, and <=10 years of experience in CER, and piecemeal resection only
in ESD. CONCLUSIONS: En bloc ESD reduces the local recurrence rate for large
colorectal neoplasias. Piecemeal resection is the most important risk factor for
local recurrence regardless of the ER method used.
PMID- 25848927
TI - Injection Drug Use and Hepatitis C as Risk Factors for Mortality in HIV-Infected
Individuals: The Antiretroviral Therapy Cohort Collaboration.
AB - BACKGROUND: HIV-infected individuals with a history of transmission through
injection drug use (IDU) have poorer survival than other risk groups. The extent
to which higher rates of hepatitis C (HCV) infection in IDU explain survival
differences is unclear. METHODS: Adults who started antiretroviral therapy
between 2000 and 2009 in 16 European and North American cohorts with >70%
complete data on HCV status were followed for 3 years. We estimated unadjusted
and adjusted (for age, sex, baseline CD4 count and HIV-1 RNA, AIDS diagnosis
before antiretroviral therapy, and stratified by cohort) mortality hazard ratios
for IDU (versus non-IDU) and for HCV-infected (versus HCV uninfected). RESULTS:
Of 32,703 patients, 3374 (10%) were IDU; 4630 (14%) were HCV+; 1116 (3.4%) died.
Mortality was higher in IDU compared with non-IDU [adjusted HR 2.71; 95%
confidence interval (CI): 2.32 to 3.16] and in HCV+ compared with HCV- (adjusted
HR 2.65; 95% CI: 2.31 to 3.04). The effect of IDU was substantially attenuated
(adjusted HR 1.57; 95% CI: 1.27 to 1.94) after adjustment for HCV, while
attenuation of the effect of HCV was less substantial (adjusted HR 2.04; 95% CI:
1.68 to 2.47) after adjustment for IDU. Both IDU and HCV were strongly associated
with liver-related mortality (adjusted HR 10.89; 95% CI: 6.47 to 18.3 for IDU and
adjusted HR 14.0; 95% CI: 8.05 to 24.5 for HCV) with greater attenuation of the
effect of IDU (adjusted HR 2.43; 95% CI: 1.24 to 4.78) than for HCV (adjusted HR
7.97; 95% CI: 3.83 to 16.6). Rates of CNS, respiratory and violent deaths
remained elevated in IDU after adjustment for HCV. CONCLUSIONS: A substantial
proportion of the excess mortality in HIV-infected IDU is explained by HCV
coinfection. These findings underscore the potential impact on mortality of new
treatments for HCV in HIV-infected people.
PMID- 25848928
TI - Trace elements in Thunnus thynnus from Mediterranean Sea and benefit-risk
assessment for consumers.
AB - Trace elemental levels were determined by inductively coupled plasma-mass
spectrometry in muscle, eggs and sperm of 23 Thunnus thynnus fishes collected
from May to August 2013 in the Mediterranean Sea. Zn, Mn, Fe, Cu, Cr, Ni and Se
content was compared with Recommended Daily Allowances. Cd, Hg and Pb
concentrations were below the maximum limits fixed by the European Legislation.
Tuna food safety was evaluated considering Tolerable Weekly Intake (TWI) or
Provisional Tolerable Weekly Intake for As, Hg, Cd and Pb. Only BMDL01 data for
As and Pb were calculated as established by the Joint FAO/WHO Expert Committed on
Food Additives. The daily consumption of fresh tuna ensures a good intake of
these elements. None of the tested samples surpassed the European maximum limits.
Cd, Hg and Pb remained within safety margins, while As is slightly higher than
the provisional TWI.
PMID- 25848930
TI - Small molecule-triggered Cas9 protein with improved genome-editing specificity.
AB - Directly modulating the activity of genome-editing proteins has the potential to
increase their specificity by reducing activity following target locus
modification. We developed Cas9 nucleases that are activated by the presence of a
cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen
responsive intein at specific positions in Cas9. In human cells, conditionally
active Cas9s modify target genomic sites with up to 25-fold higher specificity
than wild-type Cas9.
PMID- 25848932
TI - Natural radioactivity and radiation hazards assessment of soil samples from the
area of Tuzla and Lukavac, Bosnia and Herzegovina.
AB - The results of activity concentration measurements of natural occurring
radioactive nuclides (238)U, (235)U, (232)Th, (226)Ra, and (40)K in surface soil
samples collected in the area of cities Tuzla and Lukavac, northeast region of
Bosnia and Herzegovina were presented. Soil sampling was conducted at the
localities that are situated in the vicinity of industrial zones of these cities.
The measured activity was in the range from (8 +/- 4) to (95 +/- 28) Bq kg(-1)
for (238)U, from (0.41 +/- 0.06) to (4.6 +/- 0.7) Bq kg(-1) for (235)U, from (7
+/- 1) to (66 +/- 7) Bq kg(-1) for (232)Th, from (6 +/- 1) to (55 +/- 6) Bq kg(
1) for (226)Ra, and from (83 +/- 12) to (546 +/- 55) Bq kg(-1) for (40)K. In
order to evaluate the radiological hazard of the natural radioactivity for people
living near industrial zones, the absorbed dose rate, the annual effective dose
and the radium equivalent activity have been calculated and compared with the
internationally approved values.
PMID- 25848929
TI - Specific pools of endogenous peptides are present in gametophore, protonema, and
protoplast cells of the moss Physcomitrella patens.
AB - BACKGROUND: Protein degradation is a basic cell process that operates in general
protein turnover or to produce bioactive peptides. However, very little is known
about the qualitative and quantitative composition of a plant cell peptidome, the
actual result of this degradation. In this study we comprehensively analyzed a
plant cell peptidome and systematically analyzed the peptide generation process.
RESULTS: We thoroughly analyzed native peptide pools of Physcomitrella patens
moss in two developmental stages as well as in protoplasts. Peptidomic analysis
was supplemented by transcriptional profiling and quantitative analysis of
precursor proteins. In total, over 20,000 unique endogenous peptides, ranging in
size from 5 to 78 amino acid residues, were identified. We showed that in both
the protonema and protoplast states, plastid proteins served as the main source
of peptides and that their major fraction formed outside of chloroplasts.
However, in general, the composition of peptide pools was very different between
these cell types. In gametophores, stress-related proteins, e.g., late
embryogenesis abundant proteins, were among the most productive precursors. The
Driselase-mediated protonema conversion to protoplasts led to a peptide
generation "burst", with a several-fold increase in the number of components in
the latter. Degradation of plastid proteins in protoplasts was accompanied by
suppression of photosynthetic activity. CONCLUSION: We suggest that peptide pools
in plant cells are not merely a product of waste protein degradation, but may
serve as important functional components for plant metabolism. We assume that the
peptide "burst" is a form of biotic stress response that might produce peptides
with antimicrobial activity from originally functional proteins. Potential
functions of peptides in different developmental stages are discussed.
PMID- 25848933
TI - Resveratrol Fails to Extend Life Span in the Mosquito Anopheles stephensi.
AB - Resveratrol, a plant polyphenol present in grape skins, has been theorized to
account for the "French Paradox" by explaining how red wine may decrease the
health risks associated with unhealthy diets. Resveratrol has been reported to
extend life span in several different species. Other studies, however, have
failed to find a resveratrol-induced life span effect. A recent meta-study
analyzing previously published survival data concluded that, although resveratrol
reliably and reproducibly extends life span in some species, its life span
effects show diminished reliability in other organisms. The data are mixed, and
it remains unclear how evolutionarily conserved resveratrol's effects on life
span are. To gain further insight into this controversy, we studied the effects
of various concentrations (200 MUM, 100 MUM, 50 MUM, or 0 MUM) of orally fed
resveratrol on the life span of the mosquito Anopheles stephensi, an important
vector of human malaria, under two different feeding treatments--sugar-fed only
or sugar-fed with intermittent blood meals. Each treatment was repeated three
times and both survivorship and mortality rates were analyzed for each replicate.
For the majority of experiments, resveratrol failed to mediate a statistically
significant effect on life span. Although there was one instance where
resveratrol significantly increased life span, there were five other instances
where resveratrol significantly decreased life span. We conclude from these data
that, under normal conditions, resveratrol does not extend life span in A.
stephensi.
PMID- 25848934
TI - The Gender of "Energy": Language, Social Theory, and Cultural Change in Women's
Lands in the United States.
AB - Within women's intentional communities, women use the phrase women's energy to
describe certain social interactions, a sense of community, and ideas about how
gender is done or performed. For example, energy can express both difference in
communication style between men and women and male dominance in social
situations. During my fieldwork in these communities, I explored how this phrase
suggests a reference to a precultural female body, but it is also sometimes used
to explicitly reject biological reasons for gender difference. The term is easily
understandable to a wide range of women from varying class backgrounds and
encompasses both the unconscious side of social interactions and a possibility
for future change.
PMID- 25848931
TI - siRNA screen identifies QPCT as a druggable target for Huntington's disease.
AB - Huntington's disease (HD) is a currently incurable neurodegenerative condition
caused by an abnormally expanded polyglutamine tract in huntingtin (HTT). We
identified new modifiers of mutant HTT toxicity by performing a large-scale
'druggable genome' siRNA screen in human cultured cells, followed by hit
validation in Drosophila. We focused on glutaminyl cyclase (QPCT), which had one
of the strongest effects on mutant HTT-induced toxicity and aggregation in the
cell-based siRNA screen and also rescued these phenotypes in Drosophila. We found
that QPCT inhibition induced the levels of the molecular chaperone alphaB
crystallin and reduced the aggregation of diverse proteins. We generated new QPCT
inhibitors using in silico methods followed by in vitro screening, which rescued
the HD-related phenotypes in cell, Drosophila and zebrafish HD models. Our data
reveal a new HD druggable target affecting mutant HTT aggregation and provide
proof of principle for a discovery pipeline from druggable genome screen to drug
development.
PMID- 25848935
TI - Probiotics, prebiotics, and microencapsulation: A review.
AB - The development of a suitable technology for the production of probiotics is a
key research for industrial production, which should take into account the
viability and the stability of the organisms involved. Microbial criteria, stress
tolerance during processing, and storage of the product constitute the basis for
the production of probiotics. Generally, the bacteria belonging to the genera
Lactobacillus and Bifidobacterium have been used as probiotics. Based on their
positive qualities, probiotic bacteria are widely used in the production of food.
Interest in the incorporation of the probiotic bacteria into other products apart
from dairy products has been increasing and represents a great challenge. The
recognition of dose delivery systems for probiotic bacteria has also resulted in
research efforts aimed at developing probiotic food outside the dairy sector.
Producing probiotic juices has been considered more in the recent years, due to
an increased concern in personal health of consumers. This review focuses on
probiotics, prebiotics, and the microencapsulation of living cells.
PMID- 25848936
TI - Formaldehyde N,N-dialkylhydrazones as neutral formyl anion equivalents in iridium
catalyzed asymmetric allylic substitution.
AB - The use of formaldehyde N,N-dialkylhydrazones as neutral C1-nucleophiles in the
iridium-catalyzed substitution of allylic carbonates is described for two
processes. Kinetic resolution or, alternatively, stereospecific substitution
affords configurationally stable alpha,alpha-disubstituted aldehyde hydrazones in
high enantiomeric excess and yield. This umpolung approach allows for the
construction of optically active allylic nitriles and dithiolanes as well as
branched alpha-aryl aldehydes. A catalyst-controlled reaction with Enders' chiral
hydrazone derivatives followed by diastereoselective nucleophilic addition to the
hydrazone products constitutes a two-step stereodivergent synthesis of chiral
amines.
PMID- 25848937
TI - Team-Sport Athletes' Improvement of Performance on the Yo-Yo Intermittent
Recovery Test Level 2, but Not of Time-Trial Performance, With Intermittent
Hypoxic Training.
AB - PURPOSE: To determine the time course for physical-capacity adaptations to
intermittent hypoxic training (IHT) in team-sport athletes and the time course
for benefits remaining after IHT. METHODS: A pre-post parallel-groups design was
employed, with 21 Australian footballers assigned to IHT (n = 10) or control
(CON; n = 11) matched for training load. IHT performed eleven 40-min bike
sessions at 2500-m altitude over 4 wk. Yo-Yo Intermittent Recovery Test level 2
(Yo-Yo IR2) was performed before; after 3, 6, and 11 IHT sessions; and 30 and 44
d after IHT. Repeated time trials (2- and 1-km TTs, with 5 min rest) were
performed before, after, and 3 wk after IHT. Hemoglobin mass (Hb(mass)) was
measured in IHT before and after 3, 6, 9, and 11 sessions. RESULTS: Baseline Yo
Yo IR2 was similar between groups. After 6 sessions, the change in Yo-Yo IR2 in
IHT was very likely higher than CON (27% greater change, effect size 0.77, 90%
confidence limits 0.20;1.33) and likely higher 1 d after IHT (23%, 0.68,
0.05;1.30). The IHT group's change remained likely higher than CON 30 d after IHT
(24%, 0.72, 0.12;1.33) but was not meaningfully different 44 d after (12%, 0.36,
0.24;0.97). The change in 2-km TT performance between groups was not different
throughout. For 1-km TT, CON improved more after IHT, but IHT maintained
performance better after 3 wk. Hb(mass) was higher after IHT (2.7%, 0.40,
0.40;1.19). CONCLUSION: Short-duration IHT increased Yo-Yo IR2 compared with
training-load-matched controls in 2 wk. An additional 2 wk of IHT provided no
further benefit. These changes remained until at least 30 d posttraining. IHT
also protected improvement in 1-km TT.
PMID- 25848938
TI - Socioeconomic indicators of health inequalities and female mortality: a nested
cohort study within the United Kingdom Collaborative Trial of Ovarian Cancer
Screening (UKCTOCS).
AB - BACKGROUND: Evidence is mounting that area-level socioeconomic indicators are
important tools for predicting health outcomes. However, few studies have
examined these alongside individual-level education. This nested cohort study
within the control arm of the United Kingdom Collaborative Trial of Ovarian
Cancer Screening (UKCTOCS) assesses the association of mutually adjusted
individual (education) and area-level (Index of Multiple Deprivation-IMD 2007)
socioeconomic status indicators and all-cause female mortality. METHODS:
Participants resident in England who had completed both baseline (Wave 1) and
follow up (Wave 2) questionnaires were included. Follow-up was through the Health
and Social Care Information Centre with deaths censored on 31st December 2012.
IMD, education and a range of covariates were explored. Cox regression models
adjusted for all covariates were used. Sensitivity analysis using imputation was
performed (1) including those with missing data and (2) on the entire cohort who
had completed the baseline questionnaire. RESULTS: Of the 54,539 women resident
in England who completed both Wave 1 and Wave 2 questionnaires, 4,510 had missing
data. The remaining 50,029 women were included in the primary analysis. Area
level IMD was positively associated with all-cause mortality for the most
deprived group compared to the least deprived (HR=1.42, CI=1.14-1.78) after
adjusting for all potential confounders. Sensitivity analyses showed similar
results with stronger associations in the entire cohort (HR=1.90, CI=1.68-2.16).
The less educated an individual, the higher the mortality risk (test for trend
p=<0.001). However, the crude effect on mortality of having no formal education
compared to college/university education disappeared when adjusted for IMD rank
(HR=1.08, CI=0.93-1.26). CONCLUSION: Women living in more deprived areas continue
to have higher mortality even in this less deprived cohort and after adjustment
for a range of potential confounders. TRIAL REGISTRATION: This study is
registered as an International Standard Randomised Controlled Trial, number
ISRCTN22488978.
PMID- 25848939
TI - Variation at FCGR2A and functionally related genes is associated with the
response to anti-TNF therapy in rheumatoid arthritis.
AB - OBJECTIVE: Anti-TNF therapies have been highly efficacious in the management of
rheumatoid arthritis (RA), but 25-30% of patients do not show a significant
clinical response. There is increasing evidence that genetic variation at the Fc
receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to
validate this genetic association in a patient cohort from the Spanish
population, and also to identify new genes functionally related to FCGR2A that
are also associated with anti-TNF response. METHODS: A total of 348 RA patients
treated with an anti-TNF therapy were included and genotyped for FCGR2A
polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was
tested for association globally and independently for each anti-TNF drug
(infliximab, etanercept and adalimumab). Using gene expression profiles from
macrophages obtained from synovial fluid of RA patients, we searched for genes
highly correlated with FCGR2A expression. Tag SNPs were selected from each
candidate gene and tested for association with the response to therapy. RESULTS:
We found a significant association between FCGR2A and the response to adalimumab
(P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also
found a significant association between FCGR2A and the response to infliximab
(P=0.035). DHX32 and RGS12 were the most consistently correlated genes with
FCGR2A expression in RA synovial fluid macrophages (P<0.001). We found a
significant association between the genetic variation at DHX32 (rs12356233,
corrected P=0.019) and a nominally significant association between RGS12 and the
response to adalimumab (rs4690093, uncorrected P=0.040). In the anti-CCP positive
group of patients, we also found a nominally significant association between
RGS12 and the response to infliximab (rs2857859, uncorrected P=0.042).
CONCLUSIONS: In the present study we have validated the FCGR2A association in an
independent population, and we have identified new genes associated with the
response to anti-TNF therapy in RA.
PMID- 25848940
TI - EDB Fibronectin Specific Peptide for Prostate Cancer Targeting.
AB - Extradomain-B fibronectin (EDB-FN), one of the oncofetal fibronectin (onfFN)
isoforms, is a high-molecular-weight glycoprotein that mediates cell adhesion and
migration. The expression of EDB-FN is associated with a number of cancer-related
biological processes such as tumorigenesis, angiogenesis, and epithelial-to
mesenchymal transition (EMT). Here, we report the development of a small peptide
specific to EDB-FN for targeting prostate cancer. A cyclic nonapeptide, CTVRTSADC
(ZD2), was identified using peptide phage display. A ZD2-Cy5 conjugate was
synthesized to accomplish molecular imaging of prostate cancer in vitro and in
vivo. ZD2-Cy5 demonstrated effective binding to up-regulated EDB-FN secreted by
TGF-beta-induced PC3 cancer cells following EMT. Following intravenous
injections, the targeted fluorescent probe specifically bound to and delineated
PC3-GFP prostate tumors in nude mice bearing the tumor xenografts. ZD2-Cy5 also
showed stronger binding to human prostate tumor specimens with a higher Gleason
score (GS9) compared to those with a lower score (GS 7), with no binding in
benign prostatic hyperplasia (BPH). Thus, the ZD2 peptide is a promising strategy
for molecular imaging and targeted therapy of prostate cancer.
PMID- 25848941
TI - Lobular breast cancer: incidence and genetic and non-genetic risk factors.
AB - While most invasive breast cancers consist of carcinomas of the ductal type,
about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas
differ with respect to risk factors. Invasive lobular carcinoma is more strongly
associated with exposure to female hormones, and therefore its incidence is more
subject to variation. This is illustrated by US figures during the 1987 to 2004
period: after 12 years of increases, breast cancer incidence declined steadily
from 1999 to 2004, reflecting among other causes the decreasing use of menopausal
hormone therapy, and these variations were stronger for invasive lobular than for
invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly
associated with early menarche, late menopause and late age at first birth. As
for genetic risk factors, four high-penetrance genes are tested in clinical
practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2,
TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated
with invasive ductal carcinoma, while BRCA2 mutations are associated with both
ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion
protein, is of special interest as mutations are associated with invasive lobular
carcinoma, but never with ductal carcinoma. It was initially known as the main
susceptibility gene for gastric cancer of the diffuse type, but the excess of
breast cancers of the lobular type in CDH1 families led researchers to identify
it also as a susceptibility gene for invasive lobular carcinoma. The risk of
invasive lobular carcinoma is high in female mutation carriers, as about 50% are
expected to develop the disease. Carriers must therefore undergo intensive breast
cancer screening, with, for example, yearly magnetic resonance imaging and
mammogram starting at age 30 years.
PMID- 25848942
TI - Clinical outcomes in low risk coronary artery disease patients treated with
different limus-based drug-eluting stents--a nationwide retrospective cohort
study using insurance claims database.
AB - The clinical outcomes of different limus-based drug-eluting stents (DES) in a
real-world setting have not been well defined. The aim of this study was to
investigate the clinical outcomes of three different limus-based DES, namely
sirolimus-eluting stent (SES), Endeavor zotarolimus-eluting stent (E-ZES) and
everolimus-eluting stent (EES), using a national insurance claims database. We
identified all patients who received implantation of single SES, E-ZES or EES
between January 1, 2007 and December 31, 2009 from the National Health Insurance
claims database, Taiwan. Follow-up was through December 31, 2011 for all selected
clinical outcomes. The primary end-point was all-cause mortality. Secondary end
points included acute coronary events, heart failure needing hospitalization, and
cerebrovascular disease. Cox regression model adjusting for baseline
characteristics was used to compare the relative risks of different outcomes
among the three different limus-based DES. Totally, 6584 patients were evaluated
(n=2142 for SES, n=3445 for E-ZES, and n=997 for EES). After adjusting for
baseline characteristics, we found no statistically significant difference in the
risk of all-cause mortality in three DES groups (adjusted hazard ratio [HR]:
1.14, 95% confidence interval [CI]: 0.94-1.38, p=0.20 in E-ZES group compared
with SES group; adjusted HR: 0.77, 95% CI: 0.54-1.10, p=0.15 in EES group
compared with SES group). Similarly, we found no difference in the three stent
groups in risks of acute coronary events, heart failure needing hospitalization,
and cerebrovascular disease. In conclusion, we observed no difference in all
cause mortality, acute coronary events, heart failure needing hospitalization,
and cerebrovascular disease in patients treated with SES, E-ZES, and EES in a
real-world population-based setting in Taiwan.
PMID- 25848943
TI - Protein folding as a complex reaction: a two-component potential for the driving
force of folding and its variation with folding scenario.
AB - The Helmholtz decomposition of the vector field of probability fluxes in a two
dimensional space of collective variables makes it possible to introduce a
potential for the driving force of protein folding [Chekmarev, J. Chem. Phys. 139
(2013) 145103]. The potential has two components: one component (Phi) is
responsible for the source and sink of the folding flow, which represent,
respectively, the unfolded and native state of the protein, and the other (Psi)
accounts for the flow vorticity inherently generated at the periphery of the flow
field and provides the canalization of the flow between the source and sink. Both
components obey Poisson's equations with the corresponding source/sink terms. In
the present paper, we consider how the shape of the potential changes depending
on the scenario of protein folding. To mimic protein folding dynamics projected
onto a two-dimensional space of collective variables, the two-dimensional Muller
and Brown potential is employed. Three characteristic scenarios are considered: a
single pathway from the unfolded to the native state without intermediates, two
parallel pathways without intermediates, and a single pathway with an off-pathway
intermediate. To determine the probability fluxes, the hydrodynamic description
of the folding reaction is used, in which the first-passage folding is viewed as
a steady flow of the representative points of the protein from the unfolded to
the native state. We show that despite the possible complexity of the folding
process, the Phi-component is simple and universal in shape. The Psi-component is
more complex and reveals characteristic features of the process of folding. The
present approach is potentially applicable to other complex reactions, for which
the transition from the reactant to the product can be described in a space of
two (collective) variables.
PMID- 25848945
TI - Correction: chemopreventive efficacy of Andrographis paniculata on azoxymethane
induced aberrant colon Crypt Foci in vivo.
PMID- 25848944
TI - A new method for discovering disease-specific MiRNA-target regulatory networks.
AB - Genes and their expression regulation are among the key factors in the
comprehension of the genesis and development of complex diseases. In this
context, microRNAs (miRNAs) are post-transcriptional regulators that play an
important role in gene expression since they are frequently deregulated in
pathologies like cardiovascular disease and cancer. In vitro validation of miRNA-
targets regulation is often too expensive and time consuming to be carried out
for every possible alternative. As a result, a tool able to provide some criteria
to prioritize trials is becoming a pressing need. Moreover, before planning in
vitro experiments, the scientist needs to evaluate the miRNA-target genes
interaction network. In this paper we describe the miRable method whose purpose
is to identify new potentially relevant genes and their interaction networks
associate to a specific pathology. To achieve this goal miRable follows a system
biology approach integrating together general-purpose medical knowledge
(literature, Protein-Protein Interaction networks, prediction tools) and
pathology specific data (gene expression data). A case study on Prostate Cancer
has shown that miRable is able to: 1) find new potential miRNA-targets pairs, 2)
highlight novel genes potentially involved in a disease but never or little
studied before, 3) reconstruct all possible regulatory subnetworks starting from
the literature to expand the knowledge on the regulation of miRNA regulatory
mechanisms.
PMID- 25848946
TI - Synthesis and characterization of a series of [M2(beta-SiW8O31)2](n-) clusters
and mechanistic insight into the reorganization of {beta-SiW8O31} into {alpha
SiW9O34}.
AB - Lacunary polyoxometalates of low nuclearity are difficult to synthesize in
isolation. We report the facile synthesis of six {M2(B-beta-SiW8O31)2} clusters
(M = Co/Mn/Ni/Zn/Cu(2+), Fe(3+)) that can be employed as building blocks for the
formation of larger architectures. We show for the first time that such {B-beta
SiW8O31} lacunae are capable of reorganizing into larger Keggin lacunary species
even in the absence of an external source of tungstate. We hypothesize, based on
electrospray ionization mass spectrometry evidence obtained, not only that such a
transformation is only possible via an initial decomposition of the {SiW8}
precursor into a {SiW6}-based intermediate but also that it is this {SiW6}
species that acts as the template for the growth of the larger fragments.
PMID- 25848947
TI - Myofascial trigger points in patients with whiplash-associated disorders and
mechanical neck pain.
PMID- 25848948
TI - High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients
with advanced cancer: a phase I-II clinical trial.
AB - BACKGROUND: Biological and some clinical evidence suggest that high-dose
intravenous vitamin C (IVC) could increase the effectiveness of cancer
chemotherapy. IVC is widely used by integrative and complementary cancer
therapists, but rigorous data are lacking as to its safety and which cancers and
chemotherapy regimens would be the most promising to investigate in detail.
METHODS AND FINDINGS: We carried out a phase I-II safety, tolerability,
pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients
whose treating oncologist judged that standard-of-care or off-label chemotherapy
offered less than a 33% likelihood of a meaningful response. We documented
adverse events and toxicity associated with IVC infusions, determined pre- and
post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and
monitored objective clinical responses, mood and quality of life. Fourteen
patients were enrolled. IVC was safe and generally well tolerated, although some
patients experienced transient adverse events during or after IVC infusions. The
pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake
of vitamin C increases after chemotherapy, with no increase in urinary oxalic
acid excretion. Three patients with different types of cancer experienced
unexpected transient stable disease, increased energy and functional improvement.
CONCLUSIONS: Despite IVC's biological and clinical plausibility, career cancer
investigators currently ignore it while integrative cancer therapists use it
widely but without reporting the kind of clinical data that is normally gathered
in cancer drug development. The present study neither proves nor disproves IVC's
value in cancer therapy, but it provides practical information, and indicates a
feasible way to evaluate this plausible but unproven therapy in an academic
environment that is currently uninterested in it. If carried out in sufficient
numbers, simple studies like this one could identify specific clusters of cancer
type, chemotherapy regimen and IVC in which exceptional responses occur
frequently enough to justify appropriately focused clinical trials. TRIAL
REGISTRATION: ClinicalTrials.gov NCT01050621.
PMID- 25848949
TI - Timing of ripening initiation in grape berries and its relationship to seed
content and pericarp auxin levels.
AB - BACKGROUND: Individual berries in a grape (Vitis vinifera L.) cluster enter the
ripening phase at different times leading to an asynchronous cluster in terms of
ripening. The factors causing this variable ripening initiation among berries are
not known. Because the influence via hormonal communication of the seed on fruit
set and growth is well known across fruit species, differences in berry seed
content and resultant quantitative or qualitative differences in the hormone
signals to the pericarp likely influence the relative timing of ripening
initiation among berries of the cluster. RESULTS: At the time of the initiation
of cluster ripening (veraison), underripe green berries have higher seed content
compared to the riper berries and there is a negative correlation between the
seed weight-to-berry weight ratio (SB) and the sugar level in berries of a
cluster. Auxin levels in seeds relative to the pericarp tissues are two to 12
times higher at pre-ripening stages. The pericarp of berries with high-SB had
higher auxin and lower abscisic acid (ABA) levels compared to those with low-SB
from two weeks before veraison. In the preveraison cluster, the expression of
auxin-response factor genes was significantly higher in the pericarp of high-SB
berries and remained higher until veraison compared to low-SB berries. The
expression level of auxin-biosynthetic genes in the pericarp was the same between
both berry groups based upon similar expression activity of YUC genes that are
rate-limiting factors in auxin biosynthesis. On the other hand, in low-SB
berries, the expression of ABA-biosynthetic and ABA-inducible NCED and MYB genes
was higher even two weeks before veraison. CONCLUSIONS: Differences in the
relative seed content among berries plays a major role in the timing of ripening
initiation. Towards the end of berry maturation phase, low and high levels of
auxin are observed in the pericarp of low- and high-SB berries, respectively.
This results in higher auxin-signaling activity that lasts longer in the pericarp
of high-SB berries. In contrast, in low-SB berries, concomitant with an earlier
decrease of auxin level, the features of ripening initiation, such as increases
in ABA and sugar accumulation begin earlier.
PMID- 25848950
TI - Perpendicular Magnetic Anisotropy and Spin Glass-like Behavior in Molecular Beam
Epitaxy Grown Chromium Telluride Thin Films.
AB - Reflection high-energy electron diffraction (RHEED), scanning tunneling
microscopy (STM), vibrating sample magnetometry, and other physical property
measurements are used to investigate the structure, morphology, magnetic, and
magnetotransport properties of (001)-oriented Cr2Te3 thin films grown on
Al2O3(0001) and Si(111)-(7*7) surfaces by molecular beam epitaxy. Streaky RHEED
patterns indicate flat smooth film growth on both substrates. STM studies show
the hexagonal arrangements of surface atoms. Determination of the lattice
parameter from the atomically resolved STM image is consistent with the bulk
crystal structures. Magnetic measurements show the film is ferromagnetic, having
a Curie temperature of about 180 K, and a spin glass-like behavior was observed
below 35 K. Magnetotransport measurements show the metallic nature of the film
with a perpendicular magnetic anisotropy along the c-axis.
PMID- 25848951
TI - The default mode network and the working memory network are not anti-correlated
during all phases of a working memory task.
AB - INTRODUCTION: The default mode network and the working memory network are known
to be anti-correlated during sustained cognitive processing, in a load-dependent
manner. We hypothesized that functional connectivity among nodes of the two
networks could be dynamically modulated by task phases across time. METHODS: To
address the dynamic links between default mode network and the working memory
network, we used a delayed visuo-spatial working memory paradigm, which allowed
us to separate three different phases of working memory (encoding, maintenance,
and retrieval), and analyzed the functional connectivity during each phase within
and between the default mode network and the working memory network networks.
RESULTS: We found that the two networks are anti-correlated only during the
maintenance phase of working memory, i.e. when attention is focused on a
memorized stimulus in the absence of external input. Conversely, during the
encoding and retrieval phases, when the external stimulation is present, the
default mode network is positively coupled with the working memory network,
suggesting the existence of a dynamically switching of functional connectivity
between "task-positive" and "task-negative" brain networks. CONCLUSIONS: Our
results demonstrate that the well-established dichotomy of the human brain (anti
correlated networks during rest and balanced activation-deactivation during
cognition) has a more nuanced organization than previously thought and engages in
different patterns of correlation and anti-correlation during specific sub-phases
of a cognitive task. This nuanced organization reinforces the hypothesis of a
direct involvement of the default mode network in cognitive functions, as
represented by a dynamic rather than static interaction with specific task
positive networks, such as the working memory network.
PMID- 25848952
TI - Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
AB - The canonical Wnt/beta-catenin pathway is activated in triple-negative breast
cancer (TNBC). The activation of this pathway leads to the expression of specific
target genes depending on the cell/tissue context. Here, we analyzed the
transcriptome of two different TNBC cell lines to define a comprehensive list of
Wnt target genes. The treatment of cells with Wnt3a for 6h up-regulated the
expression (fold change > 1.3) of 59 genes in MDA-MB-468 cells and 241 genes in
HCC38 cells. Thirty genes were common to both cell lines. Beta-catenin may also
be a transcriptional repressor and we found that 18 and 166 genes were down
regulated in response to Wnt3a treatment for 6h in MDA-MB-468 and HCC38 cells,
respectively, of which six were common to both cell lines. Only half of the
activated and the repressed transcripts have been previously described as Wnt
target genes. Therefore, our study reveals 137 novel genes that may be positively
regulated by Wnt3a and 104 novel genes that may be negatively regulated by Wnt3a.
These genes are involved in the Wnt pathway itself, and also in TGFbeta, p53 and
Hedgehog pathways. Thorough characterization of these novel potential Wnt target
genes may reveal new regulators of the canonical Wnt pathway. The comparison of
our list of Wnt target genes with those published in other cellular contexts
confirms the notion that Wnt target genes are tissue-, cell line- and treatment
specific. Genes up-regulated in Wnt3a-stimulated cell lines were more strongly
expressed in TNBC than in luminal A breast cancer samples. These genes were also
overexpressed, but to a much lesser extent, in HER2+ and luminal B tumors. We
identified 72 Wnt target genes higher expressed in TNBCs (17 with a fold change
>1.3) which may reflect the chronic activation of the canonical Wnt pathway that
occurs in TNBC tumors.
PMID- 25848953
TI - Structure-Function Assessment of Mannosylated Poly(beta-amino esters) upon
Targeted Antigen Presenting Cell Gene Delivery.
AB - Antigen presenting cell (APC) gene delivery is a promising avenue for modulating
immunological outcomes toward a desired state. Recently, our group developed a
delivery methodology to elicit targeted and elevated levels of APC-mediated gene
delivery. During these initial studies, we observed APC-specific structure
function relationships with the vectors used during gene delivery that differ
from current non-APC cell lines, thus, emphasizing a need to re-evaluate vector
associated parameters in the context of APC gene transfer. Thus, we describe the
synthesis and characterization of a second-generation mannosylated poly(beta
amino ester) library stratified by molecular weight. To better understand the APC
specific structure-function relationships governing polymeric gene delivery, the
library was systematically characterized by (1) polymer molecular weight, (2)
relative mannose content, (3) polyplex biophysical properties, and (4) gene
delivery efficacy. In this library, polymers with the lowest molecular weight and
highest relative mannose content possessed gene delivery transfection
efficiencies as good as or better than commercial controls. Among this group, the
most effective polymers formed the smallest polymer-plasmid DNA complexes (~300
nm) with moderate charge densities (<10 mV). This convergence in polymer
structure and polyplex biophysical properties suggests a unique mode of action
and provides a framework within which future APC-targeting polymers can be
designed.
PMID- 25848955
TI - Giants in chest medicine: Jay A. Nadel, MD.
PMID- 25848954
TI - The E3 ubiquitin ligase HOS1 is involved in ethylene regulation of leaf expansion
in Arabidopsis.
AB - Ethylene regulates a variety of physiological processes, such as flowering,
senescence, abscission, and fruit ripening. In particular, leaf expansion is also
controlled by ethylene in Arabidopsis. Exogenous treatment with ethylene inhibits
leaf expansion, and consistently, ethylene insensitive mutants show increased
leaf area. Here, we report that the RING finger-containing E3 ubiquitin ligase
HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) regulates leaf expansion
in an ethylene signaling pathway. The HOS1-deficient mutant showed reduced leaf
area and was insensitive to ethylene perception inhibitor, silver thiosulfate
(STS). Accordingly, genes encoding ethylene signaling components were
significantly up-regulated in hos1-3. This study demonstrates that the HOS1
protein is involved in ethylene signal transduction for the proper regulation of
leaf expansion possibly under environmentally stressful conditions.
PMID- 25848956
TI - A 39-year-old woman with palpitations and dyspnea.
PMID- 25848957
TI - Methylene blue protects astrocytes against glucose oxygen deprivation by
improving cellular respiration.
AB - Astrocytes outnumber neurons and serve many metabolic and trophic functions in
the mammalian brain. Preserving astrocytes is critical for normal brain function
as well as for protecting the brain against various insults. Our previous studies
have indicated that methylene blue (MB) functions as an alternative electron
carrier and enhances brain metabolism. In addition, MB has been shown to be
protective against neurodegeneration and brain injury. In the current study, we
investigated the protective role of MB in astrocytes. Cell viability assays
showed that MB treatment significantly protected primary astrocytes from oxygen
glucose deprivation (OGD) & reoxygenation induced cell death. We also studied the
effect of MB on cellular oxygen and glucose metabolism in primary astrocytes
following OGD-reoxygenation injury. MB treatment significantly increased cellular
oxygen consumption, glucose uptake and ATP production in primary astrocytes. In
conclusion our study demonstrated that MB protects astrocytes against OGD
reoxygenation injury by improving astrocyte cellular respiration.
PMID- 25848959
TI - (77)Se nuclear spin-lattice relaxation in binary Ge-Se glasses: insights into
floppy versus rigid behavior of structural units.
AB - The mechanism of (77)Se nuclear spin-lattice relaxation is investigated in binary
Ge-Se glasses. The (77)Se nuclides in Se-Se-Se chain sites relax faster via
dipolar coupling fluctuation compared to those in Ge-Se-Ge sites shared by GeSe4
tetrahedra that relax slower via the fluctuation of the chemical shift
anisotropy. The relaxation rate for the Se-Se-Se sites decreases markedly with
increasing magnetic field, whereas that for the Ge-Se-Ge sites displays no
appreciable dependence on the magnetic field such that the extent of differential
relaxation between the two Se environments becomes small at high fields on the
order of 19.6 T. The corresponding dynamical correlation time is three orders of
magnitude shorter (~10(-9) s) for the Se-Se-Se sites, compared to that for the Ge
Se-Ge sites (~10(-6) s). The large decoupling in the time scale between these Se
environments provides direct experimental support to the commonly made assumption
that the selenium chains are mechanically floppy, and the interconnected GeSe4
tetrahedra form the rigid elements in the selenide glass structure.
PMID- 25848958
TI - Eighteenth-century genomes show that mixed infections were common at time of peak
tuberculosis in Europe.
AB - Tuberculosis (TB) was once a major killer in Europe, but it is unclear how the
strains and patterns of infection at 'peak TB' relate to what we see today. Here
we describe 14 genome sequences of M. tuberculosis, representing 12 distinct
genotypes, obtained from human remains from eighteenth-century Hungary using
metagenomics. All our historic genotypes belong to M. tuberculosis Lineage 4.
Bayesian phylogenetic dating, based on samples with well-documented dates, places
the most recent common ancestor of this lineage in the late Roman period. We find
that most bodies yielded more than one M. tuberculosis genotype and we document
an intimate epidemiological link between infections in two long-dead individuals.
Our results suggest that metagenomic approaches usefully inform detection and
characterization of historical and contemporary infections.
PMID- 25848960
TI - Pd clusters supported on amorphous, low-porosity carbon spheres for hydrogen
production from formic acid.
AB - Amorphous, low-porosity carbon spheres on the order of a few micrometers in size
were prepared by carbonization of squalane (C30H62) in supercritical CO2 at 823
K. The spheres were characterized and used as catalysts' supports for Pd. Near
edge X-ray absorption fine structure studies of the spheres revealed sp(2) and
sp(3) hybridized carbon. To activate carbons for interaction with a metal
precursor, often oxidative treatment of a support is needed. We showed that
boiling of the obtained spheres in 28 wt % HNO3 did not affect the shape and bulk
structure of the spheres, but led to creation of a considerable amount of surface
oxygen-containing functional groups and increase of the content of sp(2)
hybridized carbon on the surface. This carbon was seen by scanning transmission
electron microscopy in the form of waving graphene flakes. The H/C atomic ratio
in the spheres was relatively high (0.4) and did not change with the HNO3
treatment. Palladium was deposited by impregnation with Pd acetate followed by
reduction in H2. This gave uniform Pd clusters with a size of 2-4 nm. The Pd
supported on the original C spheres showed 2-3 times higher catalytic activity in
vapor phase formic acid decomposition and higher selectivity for H2 formation (98
99%) than those for the catalyst based on the HNO3 treated spheres. Using of such
low-porosity spheres as a catalyst support should prevent mass transfer
limitations for fast catalytic reactions.
PMID- 25848961
TI - Rough-fuzzy clustering and unsupervised feature selection for wavelet based MR
image segmentation.
AB - Image segmentation is an indispensable process in the visualization of human
tissues, particularly during clinical analysis of brain magnetic resonance (MR)
images. For many human experts, manual segmentation is a difficult and time
consuming task, which makes an automated brain MR image segmentation method
desirable. In this regard, this paper presents a new segmentation method for
brain MR images, integrating judiciously the merits of rough-fuzzy computing and
multiresolution image analysis technique. The proposed method assumes that the
major brain tissues, namely, gray matter, white matter, and cerebrospinal fluid
from the MR images are considered to have different textural properties. The
dyadic wavelet analysis is used to extract the scale-space feature vector for
each pixel, while the rough-fuzzy clustering is used to address the uncertainty
problem of brain MR image segmentation. An unsupervised feature selection method
is introduced, based on maximum relevance-maximum significance criterion, to
select relevant and significant textural features for segmentation problem, while
the mathematical morphology based skull stripping preprocessing step is proposed
to remove the non-cerebral tissues like skull. The performance of the proposed
method, along with a comparison with related approaches, is demonstrated on a set
of synthetic and real brain MR images using standard validity indices.
PMID- 25848962
TI - Correction: Genome-wide association analysis with gray matter volume as a
quantitative phenotype in first-episode treatment-naive patients with
schizophrenia.
AB - [This corrects the article DOI: 10.1371/journal.pone.0075083.].
PMID- 25848963
TI - Preventive Effect of Tephrosia purpurea on Selenite-Induced Experimental
Cataract.
AB - PURPOSE: Recent investigations have shown that phytochemical antioxidants can
scavenge free radicals and prevent various diseases like cataract. The objective
of the present study was to assess the efficacy of the Tephrosia purpurea in
preventing these changes in the lens of selenite-induced cataract models.
MATERIALS AND METHODS: Cataract was induced by a single injection of sodium
selenite (4 mg/kg, s.c.) to 9-day-old Sprague-Dawley rat pups. The treatment with
different extracts of T. purpurea was started on 10th day and continued for 30
days in pups pretreated with sodium selenite. The animals were treated orally
with either quercetin (1 mg/kg), flavonoid rich fraction (40 mg/kg) or alcohol
extract (300 mg/kg) of T. purpurea. Cataract was visualized after 30 days.
Encapsulated lenses were analyzed for reduced glutathione and malondialdehyde.
Lenses were also analyzed for total protein, insoluble protein, total nitrite,
calcium levels, protein sulfhydryl content as well as for the activities of
superoxide dismutase and Ca(2+)-ATPase. RESULTS: Morphological examination of the
rat lenses revealed normal transparent lens with minimal or partial nuclear
opacity in control whereas dense opacity developed in rat lens treated with
selenite. Both the extracts of T. purpurea produced reduction in nuclear opacity
as well as improvement in the insoluble proteins, protein sulfhydryl, total
nitrite, calcium levels and Ca(2+)-ATPase activity in lenses. The extracts
decreased malondialdehyde levels but also prevented the loss of reduced
glutathione levels. CONCLUSION: Our data suggests therapeutic potential of T.
purpurea for the treatment of cataract.
PMID- 25848964
TI - Subjective Reality: The Influence of Perceived and Objective Conversational
Valence on Binge Drinking Determinants.
AB - Previous studies have shown that interpersonal communication, and particularly
perceived conversational valence (i.e., the perceived negativity or positivity of
conversations) about health topics, influences health determinants. On the basis
of 43 dyads (N = 86) discussing the topic of alcohol consumption, this study is
the first to show that whereas perceived and objective conversational valence are
positively related, only perceived conversational valence is a significant
predictor of binge drinking attitudes and intentions. Thus, subjective reality
matters more than objective reality. Furthermore, only the perceived valence of
the participants' own contributions-and not of their conversation partners-
influences binge drinking intentions, indicating that self-persuasion is more
influential than persuasion by others. Thus, conversations in which discussants
themselves express negative opinions about unhealthy behaviors can enhance public
health.
PMID- 25848965
TI - Effects of body mass index on risks for ischemic stroke, thromboembolism, and
mortality in Chinese atrial fibrillation patients: a single-center experience.
AB - BACKGROUND: Obesity is considered to be related to recurrence of atrial
fibrillation (AF), left atrial thrombus formation, and atrial remodeling.
However, whether obesity is an independent risk factor for stroke and other
thromboembolic events is still controversial. OBJECTIVE: This study aimed to
investigate the effects of body mass index (BMI) on the risks of stroke,
thromboembolism, and mortality in AF patients. METHODS: Patients who were
diagnosed with nonvalvular AF were included in this observational, retrospective
study. The study population was stratified by BMI at baseline. The Cox
proportional hazard model was adopted to calculate adjusted hazard ratios of risk
factors for adverse clinical events (stroke, thromboembolism, and mortality).
RESULTS: A total of 1286 AF patients (males, 78.30%; mean age, 74.50 years;
94.48% paroxysmal AF) were followed up for a median of 2.1 years (IQR: 1.5-2.9
years). Overall, 159 patients died. A total of 84 strokes and 35 thromboembolic
events occurred. Multivariate analysis showed that overweight (25.0<=BMI<30.0
kg/m2) and age >=75 years were independent risk factors for ischemic stroke (both
P<0.01). Obesity (BMI >=30.0 kg/m2), age >=75 years, persistent/permanent AF, and
prior thromboembolism were independent risk factors for thromboembolism (all
P<0.05). Underweight (BMI <18.5 kg/m2), age >=75 years, prior ischemic
stroke/transient ischemic attack, renal dysfunction, and heart failure were
independent risk factors for all-cause deaths (all P<0.05). CONCLUSIONS:
Overweight or obesity may be a risk factor of ischemic stroke and thromboembolism
in AF patients. Excessive low weight is significantly associated with increased
all-cause mortality.
PMID- 25848966
TI - Structure-Based Prediction of G-Protein-Coupled Receptor Ligand Function: A beta
Adrenoceptor Case Study.
AB - The spectacular advances in G-protein-coupled receptor (GPCR) structure
determination have opened up new possibilities for structure-based GPCR ligand
discovery. The structure-based prediction of whether a ligand stimulates
(full/partial agonist), blocks (antagonist), or reduces (inverse agonist) GPCR
signaling activity is, however, still challenging. A total of 31 beta1 (beta1R)
and beta2 (beta2R) adrenoceptor crystal structures, including antagonist, inverse
agonist, and partial/full agonist-bound structures, allowed us to explore the
possibilities and limitations of structure-based prediction of GPCR ligand
function. We used all unique protein-ligand interaction fingerprints (IFPs)
derived from all ligand-bound beta-adrenergic crystal structure monomers to post
process the docking poses of known beta1R/beta2R partial/full agonists,
antagonists/inverse agonists, and physicochemically similar decoys in each of the
beta1R/beta2R structures. The systematic analysis of these 1920 unique IFP
structure combinations offered new insights into the relative impact of protein
conformation and IFP scoring on selective virtual screening (VS) for ligands with
a specific functional effect. Our studies show that ligands with the same
function can be efficiently classified on the basis of their protein-ligand
interaction profile. Small differences between the receptor conformation (used
for docking) and reference IFP (used for scoring of the docking poses) determine,
however, the enrichment of specific ligand types in VS hit lists. Interestingly,
the selective enrichment of partial/full agonists can be achieved by using
agonist IFPs to post-process docking poses in agonist-bound as well as antagonist
bound structures. We have identified optimal structure-IFP combinations for the
identification and discrimination of antagonists/inverse agonist and partial/full
agonists, and defined a predicted IFP for the small full agonist norepinephrine
that gave the highest retrieval rate of agonists over antagonists for all
structures (with an enrichment factor of 46 for agonists and 8 for antagonists on
average at a 1% false-positive rate). This beta-adrenoceptor case study provides
new insights into the opportunities for selective structure-based discovery of
GPCR ligands with a desired function and emphasizes the importance of IFPs in
scoring docking poses.
PMID- 25848967
TI - An Abeta42 uptake and degradation via Rg3 requires an activation of caveolin,
clathrin and Abeta-degrading enzymes in microglia.
AB - We demonstrated previously that ginsenoside Rg3 enhances the expression of
macrophage scavenger receptor class A (SRA) and amyloid beta peptide 1-42
(Abeta42) uptake in BV2 cells. In this study, we investigated the biochemical and
mechanistic roles of Rg3 in human microglia and animal models to identify the
determinants that participate in restoring memory and learning in brains
disrupted by the Abeta42 peptide. SRA was expressed highly in Rg3-treated rats,
and learning and memory functions were maintained at a normal level after the
infusion of Abeta42. SRA-transfected HMO6 human microglial cells (HMO6.hSRA)
overexpressed SRA and took up a remarkable amount of Abeta42. Rg3-treated HMO6
cells showed highly enhanced SRA expression and dramatically promoted Abeta42
uptake. Moreover, high levels of clathrin and caveolin1 supported the roles of
Rg3 in endocytic biogenesis by activating p38 and extracellular signal-regulated
protein kinase signaling. Notably, both neprilysin (NEP) and insulin-degrading
enzyme (IDE) were significantly expressed by Rg3, suggesting independent and
compensatory hydrolytic activity for the Abeta peptide. In conclusion, Rg3
successfully triggered Abeta42 uptake via SRA and clathrin-/caveolae-mediated
endocytic mechanisms and further contributed to accelerate the degradation of
Abeta peptide via the increase of intracellular NEP and IDE, which may be a
promising Alzheimer's disease therapy.
PMID- 25848968
TI - Trans-Pacific RAD-Seq population genomics confirms introgressive hybridization in
Eastern Pacific Pocillopora corals.
AB - Discrepancies between morphology-based taxonomy and phylogenetic systematics are
common in Scleractinian corals. In Pocillopora corals, nine recently identified
genetic lineages disagree fundamentally with the 17 recognized Pocillopora
species, including 5 major Indo-Pacific reef-builders. Pocillopora corals
hybridize in the Tropical Eastern Pacific, so it is possible that some of the
disagreement between the genetics and taxonomy may be due to introgressive
hybridization. Here we used 6769 genome-wide SNPs from Restriction-site
Associated DNA Sequencing (RAD-Seq) to conduct phylogenomic comparisons among
three common, Indo-Pacific Pocillopora species - P. damicornis, P. eydouxi and P.
elegans - within and between populations in the Tropical Eastern Pacific (TEP)
and the Central Pacific. Genome-wide RAD-Seq comparisons of Central and TEP
Pocillopora confirm that the morphospecies P. damicornis, P. eydouxi and P.
elegans are not monophyletic, but instead fall into three distinct genetic
groups. However, hybrid samples shared fixed alleles with their respective
parental species and, even without strict monophyly, P. damicornis share a common
set of 33 species-specific alleles across the Pacific. RAD-Seq data confirm the
pattern of one-way introgressive hybridization among TEP Pocillopora, suggesting
that introgression may play a role in generating shared, polyphyletic lineages
among currently recognized Pocillopora species. Levels of population
differentiation within genetic lineages indicate significantly higher levels of
population differentiation in the Tropical Eastern Pacific than in the Central
West Pacific.
PMID- 25848969
TI - Dissecting signal and noise in diatom chloroplast protein encoding genes with
phylogenetic information profiling.
AB - Previous analyses of single diatom chloroplast protein-encoded genes recovered
results highly incongruent with both traditional phylogenies and phylogenies
derived from the nuclear encoded small subunit (SSU) gene. Our analysis here of
six individual chloroplast genes (atpB, psaA, psaB, psbA, psbC and rbcL) obtained
similar anomalous results. However, phylogenetic noise in these genes did not
appear to be correlated, and their concatenation appeared to effectively sum
their collective signal. We empirically demonstrated the value of combining
phylogenetic information profiling, partitioned Bremer support and entropy
analysis in examining the utility of various partitions in phylogenetic analysis.
Noise was low in the 1st and 2nd codon positions, but so was signal. Conversely,
high noise levels in the 3rd codon position was accompanied by high signal.
Perhaps counterintuitively, simple exclusion experiments demonstrated this was
especially true at deeper nodes where the 3rd codon position contributed most to
a result congruent with morphology and SSU (and the total evidence tree here).
Correlated with our empirical findings, probability of correct signal (derived
from information profiling) increased and the statistical significance of
substitutional saturation decreased as data were aggregated. In this regard, the
aggregated 3rd codon position performed as well or better than more slowly
evolving sites. Simply put, direct methods of noise removal (elimination of fast
evolving sites) disproportionately removed signal. Information profiling and
partitioned Bremer support suggest that addition of chloroplast data will rapidly
improve our understanding of the diatom phylogeny, but conversely also illustrate
that some parts of the diatom tree are likely to remain recalcitrant to addition
of molecular data. The methods based on information profiling have been
criticized for their numerous assumptions and parameter estimates and the fact
that they are based on quartets of taxa. Our empirical results support
theoretical arguments that the simplifying assumptions made in these methods are
robust to "real-life" situations.
PMID- 25848970
TI - A multi-gene dataset reveals a tropical New World origin and Early Miocene
diversification of croakers (Perciformes: Sciaenidae).
AB - Widely distributed groups of living animals, such as the predominantly marine
fish family Sciaenidae, have always attracted the attention of biogeographers to
document the origins and patterns of diversification in time and space. In this
study, the historical biogeography of the global Sciaenidae is reconstructed
within a molecular phylogenetic framework to investigate their origin and to test
the hypotheses explaining the present-day biogeographic patterns. Our data matrix
comprises six mitochondrial and nuclear genes in 93 globally sampled sciaenid
species from 52 genera. Within the inferred phylogenetic tree of the Sciaenidae,
we identify 15 main and well-supported lineages; some of which have not been
recognized previously. Reconstruction of habitat preferences shows repeated
habitat transitions between marine and euryhaline environments. This implies that
sciaenids can easily adapt to some variations in salinity, possibly as the
consequence of their nearshore habitats and migratory life history. Conversely,
complete marine/euryhaline to freshwater transitions occurred only three times,
in South America, North America and South Asia. Ancestral range reconstruction
analysis concomitant with fossil evidence indicates that sciaenids first
originated and diversified in the tropical America during the Oligocene to Early
Miocene before undergoing two range expansions, to Eastern Atlantic and to the
Indo-West Pacific where a maximum species richness is observed. The uncommon
biogeographic pattern identified is discussed in relation to current knowledge on
origin of gradients of marine biodiversity toward the center of origin hypothesis
in the Indo-West Pacific.
PMID- 25848971
TI - A ratiometric biosensor for metallothionein based on a dual heterogeneous electro
chemiluminescent response from a TiO2 mesocrystalline interface.
AB - An ultrasensitive dual-signal electro-chemiluminescent intelligent biosensor
constructed from superstructure TiO2 mesocrystals is proposed for the detection
of metallothionein.
PMID- 25848972
TI - Multinormal in vitro distribution of Plasmodium falciparum susceptibility to
piperaquine and pyronaridine.
AB - BACKGROUND: In 2002, the World Health Organization recommended that artemisinin
based combination therapy (ACT) be used to treat uncomplicated malaria.
Dihydroartemisinin-piperaquine and artesunate-pyronaridine are two of these new
combinations. The aim of the present work was to assess the distribution of the
in vitro values of pyronaridine (PND) and piperaquine (PPQ) and to define a cut
off for reduced susceptibility for the two anti-malarial drugs. METHODS: The
distribution and range of the 50% inhibitory concentration values (IC50) of PND
and PPQ were determined for 313 isolates obtained between 2008 and 2012 from
patients hospitalized in France for imported malaria. The statistical Bayesian
analysis was designed to answer the specific question of whether Plasmodium
falciparum has different phenotypes of susceptibility to PND and PPQ. RESULTS:
The PND IC50 values ranged from 0.6 to 84.6 nM, with a geometric mean of 21.1 +/-
16.0 nM (standard deviation). These values were classified into three components.
The PPQ IC50 values ranged from 9.8 to 217.3 nM, and the geometric mean was 58.0
+/- 34.5 nM. All 313 PPQ values were classified into four components. Isolates
with IC50 values greater than 60 nM or four-fold greater than 3D7 IC50 are
considered isolates that have reduced susceptibility to PND and those with IC50
values greater than 135 nM or 2.3-fold greater than 3D7 IC50 are considered
isolates that have reduced susceptibility to PPQ. CONCLUSION: The existence of at
least three phenotypes for PND and four phenotypes for PPQ was demonstrated.
Based on the cut-off values, 18 isolates (5.8%) and 13 isolates (4.2%)
demonstrated reduced susceptibility to PND and PPQ, respectively.
PMID- 25848973
TI - Correlation of plasma catestatin level and the prognosis of patients with acute
myocardial infarction.
AB - Catestatin is a peptide which is a potent inhibitor of catecholamine secretion
and played essential functions in the cardiovascular system. Previous research
found that dramatic changes of catestatin were associated with hemodynamics in
acute myocardial infarction (AMI) during the first week after the AMI symptoms
onset, but whether catestatin is also involved in the pathophysiological
progression after AMI and then a predictor for outcomes is not clear. The aim of
this study is to determine the correlation of plasma catestatin levels at
different time points and the prognosis of AMI. 100 participants recruited were
all patients with AMI, all of who received successful primary percutaneous
coronary intervention (PCI) within 12h from the AMI symptom onset in our center;
the concentrations of plasma catestatin were evaluated from blood samples of
those 100 participants. Subsequent 65 months' follow-up was performed after
discharging to evaluate cardiac adverse events and the association between
catestatin levels and prognosis of AMI was examined. We confirmed the dramatic
change of catestatin concentrations in the first week of AMI, and the levels of
catestatin on D3 were much higher in adverse events group than those in non
adverse events group (p<0.0001), but the ratio of D7/D3 was significantly lower.
In addition, the Kaplan-Meier analysis showed that the groups in which the levels
on D3 were higher (p<0.0001) and the ratios of D7/D3 were lower (p<0.0001),
patients trended to be more susceptive to adverse events after AMI. Furthermore,
according to the analysis, we surmised catestatin level on D3 as an appropriate
predictor for outcomes in patients with AMI with good specificity as well as
sensitivity. All of the evidence confirmed that catestatin plays an important
role in the progress of AMI, and may act as a promising target for prognostic
prediction.
PMID- 25848974
TI - New acylated anthocyanins from purple yam and their antioxidant activity.
AB - Purple yam (Dioscorea alata L.), which is widely distributed in tropical and
subtropical regions, is characterized by its color and viscosity. Previous
studies have shown that purple yams contain a variety of acylated anthocyanins
that exhibit higher levels of antioxidant activity than the corresponding
nonacylated compounds. In this study, the pigments found in purple yams from the
Philippines (D. alata) were isolated and evaluated in terms of antioxidant
activity. Four new acylated anthocyanins, alanins (1-4) were isolated from the
MeOH extracts of purple yam, which were subsequently determined to be cyanidin
(1, 2, and 4) and peonidin (3) type compounds, along with four known anthocyanins
(5-8). The structures of 1-4 were determined by spectroscopic methods, including
NMR and MS analyses. The antioxidant activities of anthocyanins 1-8 were
investigated using oxygen radical absorbing capacity and ferric reducing
antioxidant power assays.
PMID- 25848975
TI - A combined molecular dynamic and quantum mechanic study of the solvent and guest
molecule effect on the stability and length of heterocyclic peptide nanotubes.
AB - Molecular dynamic simulations were performed to investigate the stability of
heterocyclic peptide nanotubes composed of 1,4-disubstituted-1,2,3-triazol
epsilon-amino acid. 45 ns MD simulations were conducted on the cyclic peptide
nanotube (CPNT) and cyclic peptide dimer in methanol, chloroform, and water and
revealed that these structures are more stable in nonpolar solvents. MM-PBSA and
MM-GBSA calculations were employed to analyze the solvent effect on the stability
and length of the CPNT. These calculations showed that CPNT in chloroform was
more stable and longer as compared to other solvents. In addition, the effect of
the guest molecule (ethanol) inside the dimer and CPNT was investigated. The
obtained results confirmed that guest molecule(s) stabilized the dimer and CPNT
in all solvents. Quantum chemistry calculations on the cyclic peptide dimer were
performed at the M06-2X/6-31G(d) level in the gas phase and three solvents. The
obtained results from the quantum chemistry study were in good agreement with the
MD simulation results. DFT calculations showed that the guest molecule stabilized
the dimer structure and electrostatically interacted with the cyclic peptide
dimer. Finally, for investigation of the solvent effects on the hydrogen bonds of
the cyclic peptide dimer, NBO and AIM analysis were performed.
PMID- 25848976
TI - Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood
Levels, Risk, and Outcomes.
AB - Recent investigation has identified association of IL-12p40 blood levels with
melanoma recurrence and patient survival. No studies have investigated
associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL
12p40 blood levels or their potential contributions to melanoma susceptibility or
patient outcome. In the current study, 818,237 SNPs were available for 1,804
melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573
cases (discovery), 249 cases (case validation), and 299 controls (control
validation). SNPs were evaluated for association with log[IL-12p40] levels in the
discovery data set and replicated in two validation data sets, and significant
SNPs were assessed for association with melanoma susceptibility and patient
outcomes. The most significant SNP associated with log[IL-12p40] was in the IL
12B gene region (rs6897260, combined P=9.26 * 10(-38)); this single variant
explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1
was rs6895454 (combined P=2.24 * 10(-9)). A marker in IL12B was associated with
melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00
2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in
advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11
3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40
polymorphisms may contribute to melanoma susceptibility and influence patient
outcome.
PMID- 25848977
TI - Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a
Potential Therapeutic Target.
AB - Cutaneous T-cell lymphomas (CTCLs) form a heterogeneous group of non-Hodgkin's
lymphomas characterized by only poor prognosis in advanced stage. Despite
significant progress made in the identification of novel genes and pathways
involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of
these findings has still to be proven. Here, we demonstrate by gene expression
arrays that Aurora kinase A is one of the highly overexpressed genes of the
serine/threonine kinase in CTCL. The finding was confirmed by quantitative
reverse transcriptase-PCR, western blotting, and immunohistochemistry in CTCL
cell lines and primary patient samples. Moreover, treatment with a specific
Aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest
in G2 phase, as well as apoptosis in CTCL cell lines. These data provide a
promising rationale for using Aurora kinase A inhibition as a therapeutic
modality of CTCL.
PMID- 25848978
TI - Molecular and Morphological Characterization of Inflammatory Infiltrate in
Rosacea Reveals Activation of Th1/Th17 Pathways.
AB - Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our
knowledge about an involvement of the adaptive immune system is very limited. We
performed detailed transcriptome analysis, quantitative real-time reverse
transcriptase-PCR, and quantitative immunohistochemistry on facial biopsies of
rosacea patients, classified according to their clinical subtype. As controls, we
used samples from patients with facial lupus erythematosus and healthy controls.
Our study shows significant activation of the immune system in all subtypes of
rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a
disease with significant influx of proinflammatory cells. The T-cell response is
dominated by Th1/Th17-polarized immune cells, as demonstrated by significant
upregulation of IFN-gamma or IL-17, for example. Chemokine expression patterns
support a Th1/Th17 polarization profile of the T-cell response. Macrophages and
mast cells are increased in all three subtypes of rosacea, whereas neutrophils
reach a maximum in papulopustular rosacea. Our studies also provide evidence for
the activation of plasma cells with significant antibody production already in
ETR, followed by a crescendo pattern toward phymatous rosacea. In sum, Th1/Th17
polarized inflammation and macrophage infiltration are an underestimated hallmark
in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are
promising candidates in the future treatment of this skin disease.
PMID- 25848979
TI - Differential Changes in the Peptidergic and the Non-Peptidergic Skin Innervation
in Rat Models for Inflammation, Dry Skin Itch, and Dermatitis.
AB - Skin innervation is a dynamic process that may lead to changes in nerve fiber
density during pathological conditions. We have investigated changes in epidermal
nerve fiber density in three different rat models that selectively produce
chronic itch (the dry skin model), or itch and inflammation (the dermatitis
model), or chronic inflammation without itch (the CFA model). In the epidermis,
we identified peptidergic fibers-that is, immunoreactive (IR) for calcitonin gene
related peptide or substance P-and non-peptidergic fibers-that is, IR for P2X3.
The overall density of nerve fibers was determined using IR for the protein gene
product 9.5. In all three models, the density of epidermal peptidergic nerve
fibers increased up to five times when compared with a sham-treated control
group. In contrast, the density of epidermal non-peptidergic fibers was not
increased, except for a small but significant increase in the dry skin model.
Chronic inflammation showed an increased density of peptidergic fibers without
itch, indicating that increased nerve fiber density is not invariably associated
with itch. The finding that different types of skin pathology induced
differential changes in nerve fiber density may be used as a diagnostic tool in
humans, through skin biopsies, to identify different types of pathology and to
monitor the effect of therapies.
PMID- 25848981
TI - RNA-seq analysis of short fiber mutants Ligon-lintless-1 (Li 1 ) and - 2 (Li 2 )
revealed important role of aquaporins in cotton (Gossypium hirsutum L.) fiber
elongation.
AB - BACKGROUND: Cotton fiber length is a key determinant of fiber quality for the
textile industry. Understanding the molecular basis of fiber elongation would
provide a means for improvement of fiber length. Ligon lintless-1 (Li 1 ) and
Ligon lintless-2 (Li 2 ) are monogenic and dominant mutations, that result in an
extreme reduction in the length of lint fiber to approximately 6 mm on mature
seeds. In a near-isogenic state with wild type (WT) cotton these two short fiber
mutants provide an excellent model system to study mechanisms of fiber
elongation. RESULTS: We used next generation sequencing (RNA-seq) to identify
common fiber elongation related genes in developing fibers of Li 1 and Li 2
mutants growing in the field and a greenhouse. We found a large number of
differentially expressed genes common to both mutants, including 531 up-regulated
genes and 652 down-regulated genes. Major intrinsic proteins or aquaporins were
one of the most significantly over-represented gene families among common down
regulated genes in Li 1 and Li 2 fibers. The members of three subfamilies of
aquaporins, including plasma membrane intrinsic proteins, tonoplast intrinsic
proteins and NOD26-like intrinsic proteins were down-regulated in short fiber
mutants. The osmotic concentration and the concentrations of soluble sugars were
lower in fiber cells of both short fiber mutants than in WT, whereas the
concentrations of K+ and malic acid were significantly higher in mutants during
rapid cell elongation. CONCLUSIONS: We found that the aquaporins were the most
down-regulated gene family in both short fiber mutants. The osmolality and
concentrations of soluble sugars were less in saps of Li 1 - Li 2 , whereas the
concentrations of malic acid, K+ and other detected ions were significantly
higher in saps of mutants than in WT. These results suggest that higher
accumulation of ions in fiber cells, reduced osmotic pressure and low expression
of aquaporins, may contribute to the cessation of fiber elongation in Li 1 and Li
2 short-fiber mutants. The research presented here provides new insights into
osmoregulation of short fiber mutants and the role of aquaporins in cotton fiber
elongation.
PMID- 25848980
TI - IQGAP1 and IQGAP3 Serve Individually Essential Roles in Normal Epidermal
Homeostasis and Tumor Progression.
AB - IQ motif-containing GTPase-activating protein (IQGAP) scaffolding proteins
regulate many essential cellular processes including growth factor receptor
signaling, cytoskeletal rearrangement, adhesion, and proliferation and are highly
expressed in many cancers. Using genetically engineered human skin tissue in
vivo, we demonstrate that diminished, sub-physiologic expression of IQGAP1 or
IQGAP3 is sufficient to maintain normal epidermal homeostasis, whereas
significantly higher levels are required to support tumorigenesis. To target this
tumor-specific IQGAP requirement in vivo, we engineered epidermal keratinocytes
to express individual IQGAP protein domains designed to compete with endogenous
IQGAPs for effector protein binding. Expression of the IQGAP1-IQ motif decoy
domain in epidermal tissue in vivo inhibits oncogenic Ras-driven mitogen
activated protein kinase signaling and antagonizes tumorigenesis, without
disrupting normal epidermal proliferation or differentiation. These findings
define essential non-redundant roles for IQGAP1 and IQGAP3 in the epidermis and
demonstrate the potential of IQGAP antagonism for cancer therapy.
PMID- 25848982
TI - Mammary gland tumor promotion by chronic administration of IGF1 and the insulin
analogue AspB10 in the p53R270H/+WAPCre mouse model.
AB - INTRODUCTION: Insulin analogues are structurally modified molecules with altered
pharmaco-kinetic and -dynamic properties compared to regular human insulin used
by diabetic patients. While these compounds are tested for undesired mitogenic
effects, an epidemiological discussion is ongoing regarding an association
between insulin analogue therapy and increased cancer incidence, including breast
cancer. Standard in vivo rodent carcinogenesis assays do not pick up this
possible increased carcinogenic potential. METHODS: Here we studied the role of
insulin analogues in breast cancer development. For this we used the human
relevant mammary gland specific p53R270H/+WAPCre mouse model. Animals received
life long repeated treatment with four different insulin (-like) molecules:
normal insulin, insulin glargine, insulin X10 (AspB10) or insulin-like growth
factor 1 (IGF1). RESULTS: Insulin-like molecules with strong mitogenic signaling,
insulin X10 and IGF1, significantly decreased the time for tumor development.
Yet, insulin glargine and normal insulin, did not significantly decrease the
latency time for (mammary gland) tumor development. The majority of tumors had an
epithelial to mesenchymal transition phenotype (EMT), irrespective of treatment
condition. Enhanced extracellular signaling related kinase (Erk) or
serine/threonine kinase (Akt) mitogenic signaling was in particular present in
tumors from the insulin X10 and IGF1 treatment groups. CONCLUSIONS: These data
indicate that insulin-like molecules with enhanced mitogenic signaling increase
the risk of breast cancer development. Moreover, the use of a tissue specific
cancer model, like the p53R270H/+WAPCre mouse model, is relevant to assess the
intrinsic pro-carcinogenic potential of mitogenic and non-mitogenic biologicals
such as insulin analogues.
PMID- 25848983
TI - Functionalized iron oxide nanoparticles for controlling the movement of immune
cells.
AB - Immunotherapy is currently being investigated for the treatment of many diseases,
including cancer. The ability to control the location of immune cells during or
following activation would represent a powerful new technique for this field.
Targeted magnetic delivery is emerging as a technique for controlling cell
movement and localization. Here we show that this technique can be extended to
microglia, the primary phagocytic immune cells in the central nervous system. The
magnetized microglia were generated by loading the cells with iron oxide
nanoparticles functionalized with CpG oligonucleotides, serving as a proof of
principle that nanoparticles can be used to both deliver an immunostimulatory
cargo to cells and to control the movement of the cells. The nanoparticle
oligonucleotide conjugates are efficiently internalized, non-toxic, and
immunostimulatory. We demonstrate that the in vitro migration of the adherent,
loaded microglia can be controlled by an external magnetic field and that
magnetically-induced migration is non-cytotoxic. In order to capture video of
this magnetically-induced migration of loaded cells, a novel 3D-printed "cell
box" was designed to facilitate our imaging application. Analysis of cell
movement velocities clearly demonstrate increased cell velocities toward the
magnet. These studies represent the initial step towards our final goal of using
nanoparticles to both activate immune cells and to control their trafficking
within the diseased brain.
PMID- 25848984
TI - A Bivalent, Chimeric Rabies Virus Expressing Simian Immunodeficiency Virus
Envelope Induces Multifunctional Antibody Responses.
AB - We previously showed that a matrix (M) gene-deleted rabies virus (RABV)-based
vaccine (RABV-DeltaM) is highly immunogenic and induces potent B cell responses
in the context of RABV infection. We speculated that RABV-DeltaM expressing HIV
proteins would also induce potent B cell responses against HIV antigens. As a
prerequisite to future studies in nonhuman primates, we completed immunogenicity
studies in mice to confirm the ability of RABV-DeltaM to induce polyfunctional B
cell responses in the context of HIV. To that end, the envelope protein from the
mac239 strain of SIV (SIVmac239Env) was cloned into RABV-DeltaM, resulting in
RABV-DeltaM-Env. Infectious virus was recovered following standard methods and
propagated on baby hamster kidney cells stably expressing RABV M [>10(7) focus
forming units (ffu)/ml]. Western blot analysis of cell lysates or of purified
virions confirmed Env expression on the surface of infected cells and within
virus particles, respectively. Positive neutralization activity against a
neutralization-sensitive SIV strain and to a lesser extent against a
neutralization-resistant SIV strain was detected in mice after a single
intramuscular inoculation with RABV-DeltaM-Env. The quality, but not quantity, of
the antibody response was enhanced via boosting with recombinant gp130 or RABV
DeltaM-Env as measured by an increase in antibody avidity and a skewing toward a
Th1-type antibody response. We also show that an intradermal inoculation induces
higher antibodies than an intramuscular or intranasal inoculation. An intradermal
inoculation of RABV-DeltaM-Env followed by a boost inoculation with recombinant
gp130 produced anti-SIV antibodies with neutralizing and nonneutralizing antibody
(nNAb) effector functions. Together, RABV-DeltaM-Env induces B cells to secrete
antibodies against SIV with the potential to clear both "free" and cell
associated virus. Strategies capable of eliciting both NAbs as well as nNAbs
might help to improve the efficacy of HIV-1 vaccines.
PMID- 25848985
TI - Understanding the contribution of native tracheobronchial structure to lung
function: CT assessment of airway morphology in never smokers.
AB - BACKGROUND: Computed tomographic (CT) airway lumen narrowing is associated with
lower lung function. Although volumetric CT measures of airways (wall volume [WV]
and lumen volume [LV]) compared to cross sectional measures can more accurately
reflect bronchial morphology, data of their use in never smokers is scarce. We
hypothesize that native tracheobronchial tree morphology as assessed by
volumetric CT metrics play a significant role in determining lung function in
normal subjects. We aimed to assess the relationships between airway size, the
projected branching generation number (BGN) to reach airways of <2mm lumen
diameter -the site for airflow obstruction in smokers- and measures of lung
function including forced expiratory volume in 1 second (FEV1) and forced
expiratory flow between 25% and 75% of vital capacity (FEF 25-75). METHODS: We
assessed WV and LV of segmental and subsegmental airways from six bronchial paths
as well as lung volume on CT scans from 106 never smokers. We calculated the
lumen area ratio of the subsegmental to segmental airways and estimated the
projected BGN to reach a <2mm-lumen-diameter airway assuming a dichotomized
tracheobronchial tree model. Regression analysis was used to assess the
relationships between airway size, BGN, FEF 25-75, and FEV1. RESULTS: We found
that in models adjusted for demographics, LV and WV of segmental and subsegmental
airways were directly related to FEV1 (P <0.05 for all the models). In adjusted
models for age, sex, race, LV and lung volume or height, the projected BGN was
directly associated with FEF 25-75 and FEV1 (P = 0.001) where subjects with lower
FEV1 had fewer calculated branch generations between the subsegmental bronchus
and small airways. There was no association between airway lumen area ratio and
lung volume. CONCLUSION: We conclude that in never smokers, those with smaller
central airways had lower airflow and those with lower airflow had less parallel
airway pathways independent of lung size. These findings suggest that variability
in the structure of the tracheobronchial tree may influence the risk of
developing clinically relevant smoking related airway obstruction.
PMID- 25848987
TI - Complete genome sequence of the lipase producing strain Burkholderia glumae PG1.
AB - The Gram-negative proteobacterium Burkholderia glumae PG1 produces a lipase of
biotechnological interest, which is used for the production of enantiopure
pharmaceuticals. In order to better understand the underlying mechanisms and
provide a basis for further studies, we present here the complete genome sequence
of B. glumae PG1.
PMID- 25848986
TI - Convergence and extrusion are required for normal fusion of the mammalian
secondary palate.
AB - The fusion of two distinct prominences into one continuous structure is common
during development and typically requires integration of two epithelia and
subsequent removal of that intervening epithelium. Using confocal live imaging,
we directly observed the cellular processes underlying tissue fusion, using the
secondary palatal shelves as a model. We find that convergence of a multi-layered
epithelium into a single-layer epithelium is an essential early step, driven by
cell intercalation, and is concurrent to orthogonal cell displacement and
epithelial cell extrusion. Functional studies in mice indicate that this process
requires an actomyosin contractility pathway involving Rho kinase (ROCK) and
myosin light chain kinase (MLCK), culminating in the activation of non-muscle
myosin IIA (NMIIA). Together, these data indicate that actomyosin contractility
drives cell intercalation and cell extrusion during palate fusion and suggest a
general mechanism for tissue fusion in development.
PMID- 25848988
TI - Complete genome sequence of oxalate-degrading bacterium Pandoraea vervacti DSM
23571(T).
AB - Pandoraea vervacti DSM 23571(T) is an oxalate metabolizing bacterium isolated
from an uncultivated field soil in Mugla, Turkey. Here, we present the first
complete genome sequence of P. vervacti DSM 23571(T). A complete pathway for
degradation of oxalate was revealed from the genome analysis. These data are
important to path new opportunities for genetic engineering in the field of
biotechnology.
PMID- 25848989
TI - Targeted gene mutation in tetraploid potato through transient TALEN expression in
protoplasts.
AB - Potato is the third largest food crop in the world, however, the high degree of
heterozygosity, the tetrasomic inheritance and severe inbreeding depression are
major difficulties for conventional potato breeding. The rapid development of
modern breeding methods offers new possibilities to enhance breeding efficiency
and precise improvement of desirable traits. New site-directed mutagenesis
techniques that can directly edit the target genes without any integration of
recombinant DNA are especially favorable. Here we present a successful pipeline
for site-directed mutagenesis in tetraploid potato through transient TALEN
expression in protoplasts. The transfection efficiency of protoplasts was 38-39%
and the site-directed mutation frequency was 7-8% with a few base deletions as
the predominant type of mutation. Among the protoplast-derived calli, 11-13%
showed mutations and a similar frequency (10%) was observed in the regenerated
shoots. Our results indicate that the site-directed mutagenesis technology could
be used as a new breeding method in potato as well as for functional analysis of
important genes to promote sustainable potato production.
PMID- 25848990
TI - Reducing the infant mortality rate of India to 20 by 2020: together we can do.
PMID- 25848991
TI - Building capacity of Indian scientists to conduct systematic reviews in child
health: an ICMR initiative.
AB - Knowledge and training in evidence-based medicine is essential for informed
clinical decision-making and treatment choices. Systematic reviews identify,
appraise and synthesize research-based evidence and present it in accessible
format. The Indian Council of Medical Research has promoted evidence-based
medicine in India by establishing an Advanced Center for evidence based medicine
that hosted the South Asian Cochrane Network and Center at the Christian Medical
College, Vellore; procuring a national subscription to The Cochrane Library
making it accessible to all Indian scientists; and establishing a Center for
Advanced research on evidence- based child health at Post Graduate Institute of
Medical Education and Research, Chandigarh. This article informs about a national
level initiative by ICMR that aims to harness the translational potential of
secondary research, by funding systematic reviews aligned to national health
priorities selected through a national competitive process; and to provide
training, mentoring, and quality assurance. A continuing scheme of funding high
quality systematic reviews on priority areas of Child Health may follow.
PMID- 25848992
TI - The remaining challenges to laboratory-based surveillance of invasive
pneumococcal disease.
PMID- 25848993
TI - Invasive pneumococcal disease and India.
PMID- 25848994
TI - Stress: a modifiable factor in the etiology of adolescent depression.
PMID- 25848995
TI - Hospital-based surveillance of invasive pneumococcal disease and pneumonia in
South Bangalore, India.
AB - OBJECTIVE: To estimate the incidence of invasive pneumococcal disease and
pneumonia, distribution of pneumococcal serotypes, and antibiotic susceptibility
in children aged 28 days to <60 months. DESIGN: Hospital-based surveillance.
SETTING: South Bangalore, India. PARTICIPANTS: 9950 children aged 28 days to <60
months with clinical suspicion of invasive pneumococcal disease or pneumonia.
RESULTS: The estimated at-risk population included 224,966 children <5 years of
age. Forty cases of invasive pneumococcal disease were identified. Estimated
invasive pneumococcal disease incidence was 17.8/100,000 with incidence being
highest among children aged 6 months to <12 months (49.9/100,000). Clinical
pneumonia syndrome was the most frequent diagnosis (12.5/100,000). Pneumococcal
serotypes included: 6A (n=6, 16.7%); 14 (n=5, 13.9%); 5 (n=4, 11.1%); 6B (n=4,
11.1%); 1, 18C, and 19A (n=3 each, 8.3%); 9V (n=2, 5.6%); and 3, 4, 10C, 18A,
18F, and 19F (n=1 each, 2.8%). Serotypes 6A, 14, 6B, 1, 18C, 19A, 9V, 4, 10C, and
18A showed antibiotic resistance. Clinical pneumonia incidence was 2109/100,000,
with incidence being highest among children aged 28 days to <6 months
(5033/100,000). Chest radiograph-confirmed pneumonia incidence was 1114/100,000,
with incidence being highest among children aged 28 days to <6 months
(2413/100,000). CONCLUSIONS: Invasive pneumococcal disease and pneumonia were
found to be common causes of morbidity in young children living in South
Bangalore, India.
PMID- 25848996
TI - Diagnostic accuracy of Indian Scale for Assessment of Autism (ISAA) in chidren
aged 2-9 years.
AB - OBJECTIVE: To determine the diagnostic accuracy of Indian Scale for Assessment of
Autism (ISAA) in children aged 2-9 year at high risk of autism, and to ascertain
the level of agreement with Childhood Autism Rating Scale (CARS). DESIGN:
Diagnostic Accuracy study. SETTING: Tertiary-level hospital. PARTICIPANTS:
Children aged between 2 and 9 year and considered to be at a high risk for autism
(delayed development, and age-inappropriate cognition, speech, social
interaction, behavior or play) were recruited. Those with diagnosed Hearing
impairment, Cerebral palsy, Attention deficit hyperactivity disorder or Pervasive
developmental disorders (PDD) were excluded. METHODS: Eligible children underwent
a comprehensive assessment by an expert. The study group comprising of PDD,
Global developmental delay (GDD) or Intellectual disability was administered ISAA
by an investigator after one week. Both evaluators were blinded. ISAA results
were compared to the Experts diagnosis and CARS scores. RESULTS: Out of 102
eligible children, 90 formed the study group (63 males, mean age 4.5y). ISAA had
a sensitivity 93.3, specificity of 97.4, positive and negative likelihood ratios
85.7 and 98.7 and positive and negative predictive values of 35.5 and 0.08,
respectively. Reliability was good and validity sub-optimal (r low, in 4/6
domains). The optimal threshold point demarcating Autism from No autism according
to Receiver Operating Characteristic curve was ISAA score of 70. Level of
agreement with CARS measured by Kappa coefficient was low (0.14). CONCLUSIONS:
The role of ISAA in 3-9 year old children at high risk for Autism is limited to
identifying and certifying Autism at ISAA score of 70. It requires re-examination
in 2-3 year olds.
PMID- 25848997
TI - Academic stress and depression among adolescents: a cross-sectional study.
AB - OBJECTIVE: To examine the relationship between academic stress and depression
among adolescents. METHODS: A cross-sectional study was conducted at higher
secondary schools in Tamil Nadu. 1120 adolescents were included in the study
after screening by MINI-kid tool. Modified Educatonal Stress Scale for
Adolescents was administered to all children. RESULTS: Adolescents who had
academic stress were at 2.4 times (95% CI=0.9-2.4) (P<0.001) higher risk of
depression than adolescents without academic stress. CONCLUSIONS: Adolescents
with severe academic stress need to be identified early as interventions to
reduce academic stress is likely to affect the occurrence and severity of
depression.
PMID- 25848998
TI - Serum IgG and IgA levels in polio and non-polio acute flaccid paralysis cases in
western Uttar Pradesh, India.
AB - OBJECTIVE: IgG and IgA immunocompetence of children with wild poliovirus
poliomyelitis and non-polio acute flaccid paralysis. METHODS: 932 cases of acute
flaccid paralysis, reported in 2008-2009, were tested for presence of polio and
non-polio enteroviruses according to the WHO standards. Serum IgA and IgG levels
were determined by sandwich ELISA. RESULTS: Mean (SD) IgA levels [0.87 (0.62)g/L;
n=28] of virologically confirmed poliomyelitis cases were lower than those of
virus negative [1.21 (0.83)g/L; n=612] and non-polio Enterovirus positive [1.22
(0.79)g/L; n=240] cases of acute flaccid paralysis. No significant difference was
observed in the concentration of IgG among these groups. CONCLUSIONS: IgA plays
an important role in protection against poliomyelitis.
PMID- 25848999
TI - Acute kidney injury in children after cardiopulmonary bypass: risk factors and
outcome.
AB - OBJECTIVE: To determine the incidence, risk factors and outcomes of acute kidney
injury in children undergoing cardiac surgery for congenital heart disease.
METHODS: We enrolled 208 patients undergoing cardiac surgery for congenital heart
disease during January 2012 to March 2013. Acute kidney injury was defined as per
Acute Kidney Injury Network criteria. RESULTS: Twenty patients had Acute kidney
injury; 14 were infants. Age <1 yr, cardiopulmonary bypass time, prolonged
ventilator requirement, pump failure, sepsis and hematological complications were
identified as independent risk factors for any degree for acute kidney injury.
All patients with acute kidney injury recovered the kidney function at the time
of discharge. CONCLUSIONS: Acute kidney injury is common in children after
cardiac surgery, especially in infants.
PMID- 25849000
TI - Surfactant replacement therapy in extremely low gestational age newborns.
AB - There is a growing body of evidence over the last years suggesting continuous
positive airway pressure (CPAP) ventilation being the first choice of ventilatory
support in newborns with extremely low gestational age, and early rescue
surfactant treatment being as effective as prophylactic therapy. The Intubation
Surfactant Extubation procedure is discussed as an alternative procedure that may
have the potential to combine the positive effects of surfactant and early CPAP.
A further mode of surfactant administration, administration via a thin
endotracheal catheter during spontaneous breathing with CPAP, has recently come
into clinical use. This less invasive surfactant administration technique shows
some short-term benefits but still cannot be recommended for general use in this
vulnerable population. Long-term follow-up studies are needed to allow new
recommendations on surfactant therapy in this high-risk population.
PMID- 25849001
TI - Portfolio-based learning and assessment.
AB - Assessment using portfolios has recently gained wider acceptance, and is being
considered relevant to several educational aspects in medicine, including
formative and summative assessment during resident training, revalidation and
continuing professional development. In this article, we provide an overview of
the use of portfolio as an assessment and learning tool. We have discussed the
rationale of using portfolio in medical education, its advantages and criticisms,
and some of the associated challenges and dilemmas.
PMID- 25849002
TI - Tetravalent dengue vaccine for children: evidence-based-medicine viewpoint.
PMID- 25849003
TI - Tetravalent dengue vaccine for children: vaccinologists viewpoint.
PMID- 25849004
TI - Tetravalent dengue vaccine for children: pediatricians viewpoint.
PMID- 25849005
TI - Primary lung abscess in early infancy.
AB - BACKGROUND: Lung abscess is rare in early infancy. CASE CHARACTERISTICS: We
report two infants with lung abscess, who presented with short respiratory
llness. INTERVENTION: Infants were managed with broad spectrum antibiotics
including Clindamycin. Needle aspiration was attempted in one case. MESSAGE: High
index of suspicion in infants with respiratory distress of prolonged duration can
help in reaching the diagnosis.
PMID- 25849006
TI - Limb girdle weakness responding to salbutamol: an Indian family with DOK7
mutation.
AB - BACKGROUND: Congenital Myasthenic Syndromes (CMS) are heterogeneous genetic
diseases. CASE CHARACTERISTICS: Two siblings presented with progressive limb
girdle weakness without significant fluctuations or ocular muscle weakness.
Repetitive nerve stimulation showed a decremental response and there was no
response to pyridostigmine therapy. OUTCOME: A trial of salbutamol produced a
remarkable, consistent improvement. Mutation in exon 5 of the DOK7 gene was found
in both siblings. MESSAGE: Patients with congenital myasthenic syndrome with DOK
7 mutation benefit remarkably with salbutamol.
PMID- 25849007
TI - Kawasaki disease with autoimmune hemolytic anemia.
AB - BACKGROUND: Association of autoimmune haemolytic anaemia has been seldom reported
with Kawasaki disease. CASE CHARACTERISTICS: A 7-month-old boy, presented with
prolonged fever, erythematous rash, severe pallor and hepatosplenomegaly.
OBSERVATIONS: Positive Direct Coombs test and coronary artery aneurysm on
echocardiography. He was managed with steroids along with intravenous
immunoglobulins and aspirin. OUTCOME: Early identification of the condition
helped in the management. MESSAGE: Patients of autoimmune hemolytic anemia with
unusual features such as prolonged fever, skin rash, and mixed antibody response
in Coombs test should be evaluated for underlying Kawasaki disease as a possible
etiology.
PMID- 25849008
TI - Let the life go on.
PMID- 25849009
TI - Infantile tremor syndrome -- down but not out.
AB - Retrospective chart review of 21 infants with infantile tremor syndrome for
vitamin B12 deficiency showed low serum vitamin B12 levels in 8/16 (50%). Of the
eight infants with normal levels, six had received vitamin B12 before referral.
Macrocytosis and low maternal serum B12 was found in 12 and seven cases each.
Treatment with vitamin B12 alone produced rapid recovery.
PMID- 25849010
TI - Impact of house-hold food insecurity on nutritional status of HIV-infected
children attending an ART centre in Tamil Nadu.
AB - We studied the level of food insecurity among households with HIV-infected
children and its relationship with childhood nutritional indicators. Among the
147 children assessed, food insecurity was present in 59% of households. Majority
of children with stunting belonged to-food insecure families. Stunting and
Underweight were more prevalent among children >5 years of age.
PMID- 25849011
TI - Knowledge and attitude of health researchers from India towards paying to publish
and open access journals.
AB - Knowledge and attitude of 2509 Indian health researchers towards open access
publishing and authors paying to publish model was evaluated. 55.6% researchers
had knowledge about open access and 76% about Author pay model. 72% of
Researchers were not interested to pay publication charges. Lack of research
grants were the primary reason for inability to pay publication charges.
PMID- 25849012
TI - Heliox use in ventilation of preterms.
PMID- 25849013
TI - Heliox use in ventilaion of newborns: authors reply.
PMID- 25849014
TI - Immunization recommendations should not be ambiguous.
PMID- 25849015
TI - IAP immunization guidelines: authors reply.
PMID- 25849016
TI - Listen to mother first.
PMID- 25849017
TI - Listen to mother first: reply.
PMID- 25849018
TI - The Peshawar peril.
PMID- 25849019
TI - Treatment guidelines for seasonal influenza: need for a rethink.
PMID- 25849020
TI - Localised gigantism.
PMID- 25849021
TI - Nevus lipomatosus cutaneous superficialis.
PMID- 25849022
TI - Fordyce's spots.
PMID- 25849023
TI - Chiral methyl-branched pheromones.
AB - Insect pheromones are some of the most interesting natural products because they
are utilized for interspecific communication between various insects, such as
beetles, moths, ants, and cockroaches. A large number of compounds of many kinds
have been identified as pheromone components, reflecting the diversity of insect
species. While this review deals only with chiral methyl-branched pheromones, the
chemical structures of more than one hundred non-terpene compounds have been
determined by applying excellent analytical techniques. Furthermore, their
stereoselective syntheses have been achieved by employing trustworthy chiral
sources and ingenious enantioselective reactions. The information has been
reviewed here not only to make them available for new research but also to
understand the characteristic chemical structures of the chiral pheromones. Since
biosynthetic studies are still limited, it might be meaningful to examine whether
the structures, particularly the positions and configurations of the branched
methyl groups, are correlated with the taxonomy of the pheromone producers and
also with the function of the pheromones in communication systems.
PMID- 25849025
TI - Correction: research blogging: indexing and registering the change in science
2.0.
PMID- 25849024
TI - A case-control analysis of oral contraceptive use and breast cancer subtypes in
the African American Breast Cancer Epidemiology and Risk Consortium.
AB - INTRODUCTION: Recent oral contraceptive (OC) use has been consistently associated
with increased risk of breast cancer, but evidence on specific breast cancer
subtypes is sparse. METHODS: We investigated recency and duration of OC use in
relation to molecular subtypes of breast cancer in a pooled analysis of data from
the African American Breast Cancer Epidemiology and Risk Consortium. The study
included 1,848 women with estrogen receptor-positive (ER+) breast cancer, 1,043
with ER-negative (ER-) breast cancer (including 494 triple negative (TN) tumors,
which do not have receptors for estrogen, progesterone, and human epidermal
growth factor 2), and 10,044 controls. Multivariable polytomous logistic
regression models were used to estimate odds ratios (ORs) and 95% confidence
intervals (CIs) for exposure categories relative to never use, controlling for
potential confounding variables. RESULTS: OC use within the previous 5 years was
associated with increased risk of ER+ (OR 1.46, 95% CI 1.18 to 1.81), ER- (OR
1.57, 95% CI 1.22 to 1.43), and TN (OR 1.78, 95% CI 1.25 to 2.53) breast cancer.
The risk declined after cessation of use but was apparent for ER+ cancer for 15
to 19 years after cessation and for ER- breast cancer for an even longer interval
after cessation. Long duration of use was also associated with increased risk of
each subtype, particularly ER-. CONCLUSIONS: Our results suggest that OC use,
particularly recent use of long duration, is associated with an increased risk of
ER+, ER-, and TN breast cancer in African American women. Research into
mechanisms that explain these findings, especially the association with ER-
breast cancer, is needed.
PMID- 25849026
TI - Chlorogenic acid improves late diabetes through adiponectin receptor signaling
pathways in db/db mice.
AB - The aim of this study was to examine the effects of chlorogenic acid (CGA) on
glucose and lipid metabolism in late diabetic db/db mice, as well as on
adiponectin receptors and their signaling molecules, to provide evidence for CGA
in the prevention of type 2 diabetes. We randomly divided 16 female db/db mice
into db/db-CGA and db/db-control (CON) groups equally; db/m mice were used as
control mice. The mice in both the db/db-CGA and db/m-CGA groups were
administered 80 mg/kg/d CGA by lavage for 12 weeks, whereas the mice in both CON
groups were given equal volumes of phosphate-buffered saline (PBS) by lavage. At
the end of the intervention, we assessed body fat and the parameters of glucose
and lipid metabolism in the plasma, liver and skeletal muscle tissues as well as
the levels of aldose reductase (AR) and transforming growth factor-beta1 (TGF
beta1) in the kidneys and measured adiponectin receptors and the protein
expression of their signaling molecules in liver and muscle tissues. After 12
weeks of intervention, compared with the db/db-CON group, the percentage of body
fat, fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) in the
db/db-CGA group were all significantly decreased; TGF-beta1 protein expression
and AR activity in the kidney were both decreased; and the adiponectin level in
visceral adipose was increased. The protein expression of adiponectin receptors
(ADPNRs), the phosphorylation of AMP-activated protein kinase (AMPK) in the liver
and muscle, and the mRNA and protein levels of peroxisome proliferator-activated
receptor alpha (PPAR-alpha) in the liver were all significantly greater. CGA
could lower the levels of fasting plasma glucose and HbA1c during late diabetes
and improve kidney fibrosis to some extent through the modulation of adiponectin
receptor signaling pathways in db/db mice.
PMID- 25849027
TI - Hydroethanolic Pistacia atlantica hulls extract improved wound healing process;
evidence for mast cells infiltration, angiogenesis and RNA stability.
AB - In Iranian traditional therapy folk, the Pistacia is used for treatment of wound
inflammation. Here in the present study, the In vivo effect of Pistacia atlantica
hulls ointment (PAO) on the wound healing process was assessed. Excision and
incision wounds were induced in rats. Three different doses of PAO were
administrated. Following 3, 7, 14 and 21 days, the tissue samples were obtained
and skin irritation ratio, hydroxyproline content, as well as immune cells,
fibroblasts, fibrocytes distribution and collagen density were analyzed.
Moreover, the cellular RNA damage examined using epi-fluorescent microscope.
Hydroethanolic extract of PAO significantly (P < 0.05) increased wound
contraction percentage and up-regulated hydroxyproline content. The animals in
medium and high dose PAO-treated groups exhibited remarkably (P < 0.05) higher
fibroblast distribution and significantly (P < 0.05) lower immune cells
infiltration. PAO up-regulated mast cells distribution on day 7 and elevated
neovascularization in a dose dependent manner. Significantly lower RNA damage was
revealed in PAO-treated animals. Our data showed that, PAO shortened the
inflammation phase by provoking the fibroblast proliferation. Moreover, PAO
enhanced mast cells distribution and infiltration, which in turn promoted the
neovascularization. Ultimately, promoted angiogenesis increased RNA stability in
different cell types. Thus, Hydroethanolic extract of PAO can be considered as an
appropriate compound for wound healing medicine.
PMID- 25849028
TI - The Potential of Canna lily for Wastewater Treatment Under Indian Conditions.
AB - Low cost treatment of polluted wastewater has become a serious challenge in most
of the urban areas of developing countries. The present study was undertaken to
investigate the potential of Canna lily towards removal of carbon, nitrogen, and
phosphorus from wastewater under sub-tropical conditions. A constructed wetland
(CW) cell supporting vegetative layer of Canna lily was used to treat wastewater
having high strength of CNP. Removal of biological oxygen demand (BOD3) and
chemical oxygen demand (COD) varied between 69.8-96.4% and 63.6-99.1%,
respectively. C. lily could efficiently remove carbon from a difficult to degrade
wastewater at COD:BOD ratio of 24.4. Simultaneous reduction in TKN and nitrate
pointed to good nitrification rates, and efficient plant assimilation as the
dominant nutrient removal mechanism in the present study. Suitable Indian agro
climatic conditions favored plant growth and no evident stress over the Canna
plant was observed. High removal rate of 809.8 mg/m(2)-day for TKN, 15.0 mg/m(2)
day for nitrate, and 164.2 mg/m(2)-day for phosphate suggests for a possible use
of Canna-based CW for wastewater treatment for small, rural, and remote Indian
communities.
PMID- 25849029
TI - Landscape variation in tree species richness in northern Iran forests.
AB - Mapping landscape variation in tree species richness (SR) is essential to the
long term management and conservation of forest ecosystems. The current study
examines the prospect of mapping field assessments of SR in a high-elevation,
deciduous forest in northern Iran as a function of 16 biophysical variables
representative of the area's unique physiography, including topography and
coastal placement, biophysical environment, and forests. Basic to this study is
the development of moderate-resolution biophysical surfaces and associated plot
estimates for 202 permanent sampling plots. The biophysical variables include:
(i) three topographic variables generated directly from the area's digital
terrain model; (ii) four ecophysiologically-relevant variables derived from
process models or from first principles; and (iii) seven variables of Landsat-8
acquired surface reflectance and two, of surface radiance. With symbolic
regression, it was shown that only four of the 16 variables were needed to
explain 85% of observed plot-level variation in SR (i.e., wind velocity, surface
reflectance of blue light, and topographic wetness indices representative of soil
water content), yielding mean-absolute and root-mean-squared error of 0.50 and
0.78, respectively. Overall, localised calculations of wind velocity and surface
reflectance of blue light explained about 63% of observed variation in SR, with
wind velocity accounting for 51% of that variation. The remaining 22% was
explained by linear combinations of soil-water-related topographic indices and
associated thresholds. In general, SR and diversity tended to be greatest for
plots dominated by Carpinus betulus (involving >= 33% of all trees in a plot),
than by Fagus orientalis (median difference of one species). This study provides
a significant step towards describing landscape variation in SR as a function of
modelled and satellite-based information and symbolic regression. Methods in this
study are sufficiently general to be applicable to the characterisation of SR in
other forested regions of the world, providing plot-scale data are available for
model generation.
PMID- 25849030
TI - The role of CD95 and CD95 ligand in cancer.
PMID- 25849031
TI - Proteolysis of virulence regulator ToxR is associated with entry of Vibrio
cholerae into a dormant state.
AB - Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the
diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and
ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio
Pathogenicity Island (VPI), a horizontally acquired mobile genetic element, and
functions primarily in virulence gene regulation. TcpP has been shown to undergo
regulated intramembrane proteolysis (RIP) in response to environmental conditions
that are unfavorable for virulence gene expression. ToxR is encoded in the
ancestral genome and is present in non-pathogenic strains of V. cholerae,
indicating it has roles outside of the human host. In this study, we show that
ToxR undergoes RIP in V. cholerae in response to nutrient limitation at alkaline
pH, a condition that occurs during the stationary phase of growth. This process
involves the site-2 protease RseP (YaeL), and is dependent upon the RpoE-mediated
periplasmic stress response, as deletion mutants for the genes encoding these two
proteins cannot proteolyze ToxR under nutrient limitation at alkaline pH. We
determined that the loss of ToxR, genetically or by proteolysis, is associated
with entry of V. cholerae into a dormant state in which the bacterium is normally
found in the aquatic environment called viable but nonculturable (VBNC). Strains
that can proteolyze ToxR, or do not encode it, lose culturability, experience a
change in morphology associated with cells in VBNC, yet remain viable under
nutrient limitation at alkaline pH. On the other hand, mutant strains that cannot
proteolyze ToxR remain culturable and maintain the morphology of cells in an
active state of growth. Overall, our findings provide a link between the
proteolysis of a virulence regulator and the entry of a pathogen into an
environmentally persistent state.
PMID- 25849032
TI - Does lower gastrointestinal endoscopy during pregnancy pose a risk for mother and
child? - a systematic review.
AB - BACKGROUND: Gastrointestinal endoscopy plays a crucial role in the diagnosis and
management of gastrointestinal disorders. When endoscopy is indicated during
pregnancy, concerns about the effects on pregnancy outcome often arise. The aim
of this study was to assess whether lower gastrointestinal endoscopies (LGEs)
across all three trimesters of pregnancy affects pregnancy outcomes. METHODS: A
systematic literature search was performed using Embase (including MEDLINE),
Medline OvidSP, Cochrane Central Register of Controlled Trials, Web-of-Science,
Google scholar and Pubmed. All original research articles from 1990 until May
2014 involving pregnant women who underwent LGE for any indication were included.
Adverse pregnancy events like spontaneous abortion, preterm birth and fetal
demise were assessed for a temporal and etiological relation with the LGE.
RESULTS: In total, 5514 references were screened by two independent reviewers.
Eighty-two references met the inclusion criteria and were selected. Two
retrospective, controlled studies, one uncontrolled study and 79 case reports
were identified. In the three studies, birth outcomes did not differ between
women undergoing LGE during pregnancy, compared to women that had an indication
for LGE but in whom LGE was not performed because of pregnancy. In 79 case
reports, 92 patients are described who underwent 100 LGE's during pregnancy. LGEs
performed in all trimesters (n = 32, 39 and 29) were both temporally and
etiologically related to 1, 3 and 2 adverse events, respectively. CONCLUSION:
Based on the available literature, this review concludes that lower
gastrointestinal endoscopy during pregnancy is of low risk for mother and child
in all three trimesters of pregnancy.
PMID- 25849035
TI - Repulsive van der waals forces self-limit native oxide growth.
AB - Silicon is one of the most studied materials, yet questions remain unanswered
about its unusual property of growing a self-limiting native oxide that attains
its final thickness in a matter of hours yet months later has not grown further.
For the first time, we have explored this self-limiting growth in terms of
repulsive van der Waals (vdW) forces generated by the combination of material
properties inherent to the system. These repulsive forces represent an energy
barrier preventing additional oxidizing chemicals, mainly oxygen and water, from
adsorbing on the surface as well as hindering diffusion of those that do adsorb
toward the interface. We have also proven that this native oxide can be increased
in thickness at room temperature and without reactive species by changing the
oxidation environment to one predicted by theory to result in attractive vdW
forces, thus allowing oxygen/water to interact with the surface more freely.
PMID- 25849033
TI - Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without
Alzheimer's dementia.
AB - INTRODUCTION: Down syndrome (DS) is associated with amyloid b (Ab) deposition.
METHODS: We characterized imaging measurements of regional fibrillar Ab burden,
cerebral metabolic rate for glucose (rCMRgl), gray matter volumes (rGMVs), and
age associations in 5 DS with dementia (DS/AD1), 12 DS without dementia (DS/AD2),
and 9 normal controls (NCs). RESULTS: There were significant group differences in
mean standard uptake value ratios (SUVRs) for florbetapir with DS/AD1 having the
highest, followed by DS/AD2, followed by NC. For [18F]-fluorodeoxyglucose
positron emission tomography, posterior cingulate rCMRgl in DS/AD1 was
significantly reduced compared with DS/AD2 and NC. For volumetric magnetic
resonance imaging (vMRI), hippocampal volumes were significantly reduced for the
DS/AD1 compared with DS/AD2 and NC. Age-related SUVR increases and rCMRgl
reductions were greater in DS participants than in NCs. DISCUSSION: DS is
associated with fibrillar Ab, rCMRgl, and rGMV alterations in the dementia stage
and before the presence of clinical decline. This study provides a foundation for
the studies needed to inform treatment and prevention in DS.
PMID- 25849034
TI - Computable cause-and-effect models of healthy and Alzheimer's disease states and
their mechanistic differential analysis.
AB - INTRODUCTION: The discovery and development of new treatments for Alzheimer's
disease (AD) requires a profound mechanistic understanding of the disease. Here,
we propose a model-driven approach supporting the systematic identification of
putative disease mechanisms. METHODS: We have created a model for AD and a
corresponding model for the normal physiology of neurons using biological
expression language to systematically model causal and correlative relationships
between biomolecules, pathways, and clinical readouts. Through model-model
comparison we identify "chains of causal relationships" that lead to new insights
into putative disease mechanisms. RESULTS: Using differential analysis of our
models we identified a new mechanism explaining the effect of amyloid-beta on
apoptosis via both the neurotrophic tyrosine kinase receptor, type 2 and nerve
growth factor receptor branches of the neurotrophin signaling pathway. We also
provide the example of a model-guided interpretation of genetic variation data
for a comorbidity analysis between AD and type 2 diabetes mellitus. DISCUSSION:
The two computable, literature-based models introduced here provide a powerful
framework for the generation and validation of rational, testable hypotheses
across disease areas.
PMID- 25849036
TI - Development of a multi-toxin method for investigating the carryover of
zearalenone, deoxynivalenol and their metabolites into milk of dairy cows.
AB - A dose-response study was carried out to examine the carryover of zearalenone
(ZEN), deoxynivalenol (DON) and their metabolites into bovine milk. Therefore, a
feeding trial with 30 dairy cows fed with three different levels of Fusarium
(FUS) toxin-contaminated maize was performed. A control group (0.02 mg ZEN kg(-1)
dry matter (DM) and 0.07 DON kg(-1) DM) was compared with two groups fed
contaminated diets. The first diet contained 0.33 mg ZEN kg(-1) DM and 2.62 mg
DON kg(-1) DM (group FUS-50) and the second diet contained 0.66 mg ZEN kg(-1) DM
and 5.24 mg DON kg(-1) DM (group FUS-100). For milk sample analysis, a new cost
efficient sample preparation method was developed for the simultaneous
determination of ZEN, DON and their metabolites. The method comprised the
separation of the milk fat followed by an SPE clean-up on Oasis HLB and a LC
MS/MS measurement. The less toxic metabolite de-epoxy-DON had the highest
detected concentration (5.6 ng ml(-1) milk) in the milk samples obtained from the
feeding trial. Additionally, ZEN (up to 0.29 ng ml(-1)), alpha-zearalenol (up to
0.17 ng ml(-1)), beta-zearalenol (up to 0.95 ng ml(-1)) and DON (up to 2.5 ng ml(
1)) were detected in these samples. The milk toxin concentrations of cows fed the
control diet were significantly lower compared with cows fed the contaminated
diet. The calculated carryover rates ranged between 0 and 0.0075 for ZEN and
metabolites and between 0 and 0.0017 for DON independent of exposure. It can be
concluded that dietary toxin concentrations in the feed below or close to the
current guidance values do not pose a risk for consumers due to negligible
carryover rates.
PMID- 25849037
TI - BTNL2 gene polymorphism and sarcoidosis susceptibility: a meta-analysis.
AB - BACKGROUND: Butyrophilin-like 2 (BTNL2) rs2076530 gene polymorphism has been
implicated in susceptibility to sarcoidosis. However, results from previous
studies are not consistent. To assess the association of BTNL2 polymorphism and
sarcoidosis susceptibility, a meta-analysis was performed. METHODS: PubMed,
Embase were searched for eligible case-control studies. Data were extracted and
pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.
RESULTS: Ten studies involving a total of 3303 cases and 2514 controls were
included in this meta-analysis. Combined data indicated that BTNL2 rs2076530
polymorphism was associated with sarcoidosis susceptibility in allelic model (A
vs. G, OR = 1.59, 95%CI: 1.47-1.72), dominant model (AA + AG vs. GG, OR = 2.10,
95%CI: 1.67-2.65), and recessive model (AA vs. AG + GG, OR = 1.93, 95%CI: 1.49
2.50). CONCLUSIONS: This meta-analysis indicates that BTNL2 rs2076530
polymorphism contributes to the risk of sarcoidosis.
PMID- 25849038
TI - A novel pyrimidin-like plant activator stimulates plant disease resistance and
promotes growth.
AB - Plant activators are chemicals that induce plant defense responses to a broad
spectrum of pathogens. Here, we identified a new potential plant activator, 5
(cyclopropylmethyl)-6-methyl-2-(2-pyridyl)pyrimidin-4-ol, named PPA (pyrimidin
type plant activator). Compared with benzothiadiazole S-methyl ester (BTH), a
functional analog of salicylic acid (SA), PPA was fully soluble in water and
increased fresh weight of rice (Oryza sativa) and Arabidopsis plants at low
concentrations. In addition, PPA also promoted lateral root development.
Microarray data and real-time PCR revealed that PPA-treated leaves not challenged
with pathogen showed up-regulation of genes related to reactive oxygen species
(ROS), defenses and SA. During bacterial infection, Arabidopsis plants pretreated
with PPA showed dramatically decreased disease symptoms and an earlier and
stronger ROS burst, compared with plants pretreated with BTH. Microscopy revealed
that H2O2 accumulated in the cytosol, plasma membrane and cell wall around
intracellular bacteria, and also on the bacterial cell wall, indicating that H2O2
was directly involved in killing bacteria. The increase in ROS-related gene
expression also supported this observation. Our results indicate that PPA
enhances plant defenses against pathogen invasion through the plant redox system,
and as a water-soluble compound that can promote plant growth, has broad
potential applications in agriculture.
PMID- 25849039
TI - Effects of asymmetric nuclear introgression, introgressive mitochondrial sweep,
and purifying selection on phylogenetic reconstruction and divergence estimates
in the Pacific clade of Locustella warblers.
AB - When isolated but reproductively compatible populations expand geographically and
meet, simulations predict asymmetric introgression of neutral loci from a local
to invading taxon. Genetic introgression may affect phylogenetic reconstruction
by obscuring topology and divergence estimates. We combined phylogenetic analysis
of sequences from one mtDNA and 12 nuDNA loci with analysis of gene flow among 5
species of Pacific Locustella warblers to test for presence of genetic
introgression and its effects on tree topology and divergence estimates. Our data
showed that nuDNA introgression was substantial and asymmetrical among all
members of superspecies groups whereas mtDNA showed no introgression except a
single species pair where the invader's mtDNA was swept by mtDNA of the local
species. This introgressive sweep of mtDNA had the opposite direction of the
nuDNA introgression and resulted in the paraphyly of the local species' mtDNA
haplotypes with respect to those of the invader. The multilocus nuDNA species
tree resolved all inter- and intraspecific relationships despite substantial
introgression. However, the node ages on the species tree may be underestimated
as suggested by the differences in node age estimates based on non-introgressing
mtDNA and introgressing nuDNA. In turn, the introgressive sweep and strong
purifying selection appear to elongate internal branches in the mtDNA gene tree.
PMID- 25849040
TI - Mosquito-disseminated pyriproxyfen yields high breeding-site coverage and boosts
juvenile mosquito mortality at the neighborhood scale.
AB - BACKGROUND: Mosquito-borne pathogens pose major public health challenges
worldwide. With vaccines or effective drugs still unavailable for most such
pathogens, disease prevention heavily relies on vector control. To date, however,
mosquito control has proven difficult, with low breeding-site coverage during
control campaigns identified as a major drawback. A novel tactic exploits the egg
laying behavior of mosquitoes to have them disseminate tiny particles of a potent
larvicide, pyriproxyfen (PPF), from resting to breeding sites, thus improving
coverage. This approach has yielded promising results at small spatial scales,
but its wider applicability remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: We
conducted a four-month trial within a 20-month study to investigate mosquito
driven dissemination of PPF dust-particles from 100 'dissemination stations'
(DSs) deployed in a 7-ha sub-area to surveillance dwellings and sentinel breeding
sites (SBSs) distributed over an urban neighborhood of about 50 ha. We assessed
the impact of the trial by measuring juvenile mosquito mortality and adult
mosquito emergence in each SBS-month. Using data from 1,075 dwelling-months,
2,988 SBS-months, and 29,922 individual mosquitoes, we show that mosquito
disseminated PPF yielded high coverage of dwellings (up to 100%) and SBSs (up to
94.3%). Juvenile mosquito mortality in SBSs (about 4% at baseline) increased by
over one order of magnitude during PPF dissemination (about 75%). This led to a
>10-fold decrease of adult mosquito emergence from SBSs, from approximately 1,000
3,000 adults/month before to about 100 adults/month during PPF dissemination.
CONCLUSIONS/SIGNIFICANCE: By expanding breeding-site coverage and boosting
juvenile mosquito mortality, a strategy based on mosquito-disseminated PPF has
potential to substantially enhance mosquito control. Sharp declines in adult
mosquito emergence can lower vector/host ratios, reducing the risk of disease
outbreaks. This approach is a very promising complement to current and novel
mosquito control strategies; it will probably be especially relevant for the
control of urban disease vectors, such as Aedes and Culex species, that often
cause large epidemics.
PMID- 25849042
TI - Theoretical Investigation on the Reaction between OH Radical and 4,4-Dimethyl-1
pentene in the Presence of O2.
AB - The atmospheric oxidation mechanism of 4,4-dimethyl-1-pentene (DMP441) initiated
by OH radical has been theoretically investigated at the BH&HLYP/6-311++G(d,p)
and CCSD(T)/6-31+G(d,p) levels of theory. HC(O)H and 3,3-dimethylbutanal
[(CH3)3CCH2C(O)H] are identified in our calculations as major products in the OH
radical-initiated degradation of DMP441 in the presence of O2. However, the
epoxide conformers and enols are expected to be minor products because of the
high isomerization barriers involved. The calculated results are in qualitative
accordance with experimental evidence. Conventional transition state theory has
been used to calculate the rate constants of the initial addition channels of the
OH + DMP441 reaction over the temperature range 220-500 K. The computed total
rate constant at 298 K is 2.20 * 10(-11) cm(3) molecule(-1) s(-1), which is in
very good agreement with the experimental value. Furthermore, it has been found
that the calculated rate constant exhibits a weak non-Arrhenius behavior over the
temperature range 220-500 K. The computed expression for the rate constant is
k(OH+DMP441) = 1.22 * 10(-12) exp[(880 K)/T] cm(3) molecule(-1) s(-1).
PMID- 25849041
TI - Catecholamines promote Actinobacillus pleuropneumoniae growth by regulating iron
metabolism.
AB - Catecholamines are host stress hormones that can induce the growth of many
bacteria by facilitating iron utilization and/or regulate the expression of
virulence genes through specific hormone receptors. Whether these two responsive
pathways are interconnected is unknown. In our previous study, it was found that
catecholamines can regulate the expression of a great number of genes of
Actinobacillus pleuropneumoniae, an important swine respiratory pathogen.
However, bacterial growth was not affected by catecholamines in rich medium. In
this study, it was discovered that catecholamines affected A. pleuropneumoniae
growth in chemically defined medium (CDM). We found that serum inhibited A.
pleuropneumoniae growth in CDM, while epinephrine, norepinephrine and dopamine
promoted A. pleuropneumoniae growth in the CDM containing serum. The known
bacterial hormone receptor QseC didn't play roles in this process. Ion
supplementation and transcriptome analysis indicated that serum addition resulted
in iron-restricted conditions which were alleviated by the addition of
catecholamines. Transferrin, one of the components in serum, inhibited the growth
of A. pleuropneumoniae in CDM, an effect reversed by addition of catecholamines
in a TonB2-dependent manner. Our data demonstrate that catecholamines promote A.
pleuropneumoniae growth by regulating iron-acquisition and metabolism, which is
independent of the adrenergic receptor QseC.
PMID- 25849043
TI - Isostructural Re(I)/(99m)Tc(I) tricarbonyl complexes for cancer theranostics.
AB - Merging classical organic anticancer drugs with metal-based compounds in one
single molecule offers the possibility of exploring new approaches for cancer
theranostics, i.e. the combination of diagnostic and therapeutic modalities. For
this purpose, we have synthesized and biologically evaluated a series of
Re(I)/(99m)Tc(I) tricarbonyl complexes (Re1-Re4 and Tc1-Tc4, respectively)
stabilized by a cysteamine-based (N,S,O) chelator and containing 2-(4'
aminophenyl)benzothiazole pharmacophores. With the exception of Re1, all the Re
complexes have shown a moderate cytotoxicity in MCF7 and PC3 cancer cells (IC50
values in the 15.9-32.1 MUM range after 72 h of incubation). The cytotoxic
activity of the Re complexes is well correlated with cellular uptake that was
quantified using the isostructural (99m)Tc congeners. There is an augmented
cytotoxic effect for Re3 and Re4 (versusRe1 and Re2), and the highest cellular
uptake for Tc3 and Tc4, which display a long ether-containing linker to couple
the pharmacophore to the (N,S,O)-chelator framework. Moreover, fluorescence
microscopy clearly confirmed the cytosolic accumulation of the most cytotoxic
compound (Re3). Biodistribution studies of Tc1-Tc4 in mice confirmed that these
moderately lipophilic complexes (logDo/w = 1.95-2.32) have a favorable
bioavailability. Tc3 and Tc4 presented a faster excretion, as they undergo
metabolic transformations, in contrast to complexes Tc1 and Tc2. In summary, our
results show that benzothiazole-containing Re(I)/(99m)Tc(I) tricarbonyl complexes
stabilized by cysteamine-based (N,S,O)-chelators have potential to be further
applied in the design of new tools for cancer theranostics.
PMID- 25849044
TI - Repeat work bouts increase thermal strain for Australian firefighters working in
the heat.
AB - BACKGROUND: Firefighters regularly re-enter fire scenes during long duration
emergency events with limited rest between work bouts. It is unclear whether this
practice is impacting on the safety of firefighters. OBJECTIVES: To evaluate the
effects of multiple work bouts on firefighter physiology, strength, and cognitive
performance when working in the heat. METHODS: Seventy-seven urban firefighters
completed two 20-minute simulated search and rescue tasks in a heat chamber (105
+/- 5 degrees C), separated by a 10-minute passive recovery. Core and skin
temperature, rate of perceived exertion (RPE), thermal sensation (TS), grip
strength, and cognitive changes between simulations were evaluated. RESULTS:
Significant increases in core temperature and perceptual responses along with
declines in strength were observed following the second simulation. No
differences for other measures were observed. CONCLUSIONS: A significant increase
in thermal strain was observed when firefighters re-entered a hot working
environment. We recommend that longer recovery periods or active cooling methods
be employed prior to re-entry.
PMID- 25849045
TI - The solar magnetic activity band interaction and instabilities that shape quasi
periodic variability.
AB - Solar magnetism displays a host of variational timescales of which the enigmatic
11-year sunspot cycle is most prominent. Recent work has demonstrated that the
sunspot cycle can be explained in terms of the intra- and extra-hemispheric
interaction between the overlapping activity bands of the 22-year magnetic
polarity cycle. Those activity bands appear to be driven by the rotation of the
Sun's deep interior. Here we deduce that activity band interaction can
qualitatively explain the 'Gnevyshev Gap'-a well-established feature of flare and
sunspot occurrence. Strong quasi-annual variability in the number of flares,
coronal mass ejections, the radiative and particulate environment of the
heliosphere is also observed. We infer that this secondary variability is driven
by surges of magnetism from the activity bands. Understanding the formation,
interaction and instability of these activity bands will considerably improve
forecast capability in space weather and solar activity over a range of
timescales.
PMID- 25849046
TI - Connective tissue diseases: ICOS sustains pathogenic T-cell survival in SLE mouse
model.
PMID- 25849047
TI - Correction: genomic, proteomic, morphological, and phylogenetic analyses of
vB_EcoP_SU10, a podoviridae phage with C3 morphology.
PMID- 25849049
TI - Comparison of the effects of neuromuscular electrical stimulation and endurance
training in patients with severe chronic obstructive pulmonary disease.
AB - INTRODUCTION: In severely disabled patients who are not capable of following
formal pulmonary rehabilitation (PR) and/or tolerating higher training
intensities, neuromuscular electrical stimulation (NMES) has been successfully
utilized as a localized training method. MATERIALS AND METHODS: In this non
randomized controlled observational study 50 patients with severe chronic
obstructive pulmonary disease (COPD), who were allocated into two groups.
Endurance training group (ET) (n= 27) and NMES group (n= 23). To compare the
effects of NMES and ET on health-related quality of life (HRQOL), exercise
capacity, muscle strength, dyspnea, psychological status, and body composition in
patients with severe COPD. Before and after PR program, the study parameters were
assessed using the Medical Research Council (MRC) scale, incremental and
endurance shuttle walking tests (ISWT, ESWT), manual muscle testing (MMT), the
St. George's Respiratory Questionnaire (SGRQ), bioelectrical impedance analysis,
and the Hospital Anxiety and Depression Scale (HADS). RESULTS: After the PR
program, walking distance and endurance time significantly increased in both
groups (p< 0.001 for each), whereas the MRC scores of both groups significantly
decreased (p< 0.001 for each). In the ET group, significant decreases were noted
in all domains of SGRQ and HADS. In the NMES group, significant improvements were
observed in the HADS scores and in all SGRQ domain except symptom domain. No
significant differences were observed between the NMES and ET groups regarding
the changes from baseline to after PR program in walking distance (p= 0.140),
endurance time (p= 0.376), the MRC (p= 0.540), HRQOL (p> 0.05) and HADS (p> 0.05)
scores, body-mass index (BMI) (p= 0.49), fat-free mass (FFM) (p= 0.50) and fat
free mass index (FFMI) (p= 0.94). CONCLUSION: NMES can be used as an effective
treatment strategy in PR programs for peripheral muscle training in patients with
severe COPD.
PMID- 25849050
TI - Economic burden of nosocomial pneumonia in non-intensive care clinics.
AB - INTRODUCTION: Almost all data on the cost of nosocomial pneumonia (NP) in the
literature is associated with ventilator-associated pneumonia. This study aims to
determine the economic burden of nosocomial pneumonia in clinical inpatients.
MATERIALS AND METHODS: Data on costs of the 154 adult patients (97 male, 57
female; mean age 64.53 +/- 14.92) who were hospitalized in non-intensive care
clinics and developed NP were recorded prospectively. The control group consisted
of 148 patients without pneumonia matched for age (mean age 65.66 +/- 13.86), sex
(94 male), diagnosis, and hospitalization date. Data obtained from both groups of
patients for the number of hospitalization days and the data obtained from the
hospital automation program (Avicenna) for costs were compared using the Mann
Whitney U test. RESULTS: While the mean duration of hospitalization was 32.8 days
in patients with NP, it was 9.8 (p< 0.0001) in the control group. The cost of
hospital beds was $631 for NP patients and $153 for the controls (p< 0.0001). The
total cost was $6241 for NP patients and $1117 for the controls (p< 0.0001).
CONCLUSION: NP is a high-cost condition that increases the duration of
hospitalization 3.5-fold, hospital-bed cost 4-fold, and the total cost 5-fold.
PMID- 25849051
TI - [Misdiagnosis of pulmonary embolism and causes].
AB - INTRODUCTION: Pulmonary thromboembolism (PTE) is not only one of the prevelant
diseases with a high mortality risk but also has a high ratio of delayed
diagnosis and misdiagnosis. In this study, it was aimed to determine the
demographical characteristics, risk factors, clinical and laboratory findings of
the patients that were diagnosed as PTE at their first hospital visit and of the
PE patients who were misdiagnosed at their first admission. We aimed to
investigate the factors which can leads to misdiagnosis of PE, and to determine
the ways to avoid misdiagnosis. MATERIALS AND METHODS: One hundred PTE patients
who were admitted to University Hospital between the dates January 2007-December
2011 were included in the study. Clinical and laboratory findings of these
patients were evaluated. Among these patients, 26 were misdiagnosed at their
first admission but diagnosed accurately (as PTE) in our hospital and 74 were
diagnosed accurately. Two groups were compared with respect to various data of
the patients clinical and demographical characteristics. RESULTS: Between the two
groups, there was no difference in terms of physical examination and laboratory
findings. The patients with the symptoms onset was over a week ago had a higher
misdiagnosis rate (p= 0.002). The patients with no risk of PTE had a higher
misdiagnosis rate (p= 0.017). Misdiagnosis rate of the patients with cardiac
diseases was lower (p= 0.033) According to Geneva risk score, we observed that
the misdiagnosis risk was reduced in the patients with higher clinical
probability (p= 0.011). CONCLUSION: In conclusion, misdiagnosis rate was found to
be statistically significant in the patients with low score according to the
Geneva risk classification, and whose pre-diagnosis period lasted for more than a
week and with no risk factors of PTE or cardiac diseases. We are in the opinion
that considering these parameters will help to reduce in misdiagnosis of
pulmonary embolism cases.
PMID- 25849048
TI - Quantitative profiling of brain lipid raft proteome in a mouse model of fragile X
syndrome.
AB - Fragile X Syndrome, a leading cause of inherited intellectual disability and
autism, arises from transcriptional silencing of the FMR1 gene encoding an RNA
binding protein, Fragile X Mental Retardation Protein (FMRP). FMRP can regulate
the expression of approximately 4% of brain transcripts through its role in
regulation of mRNA transport, stability and translation, thus providing a
molecular rationale for its potential pleiotropic effects on neuronal and brain
circuitry function. Several intracellular signaling pathways are dysregulated in
the absence of FMRP suggesting that cellular deficits may be broad and could
result in homeostatic changes. Lipid rafts are specialized regions of the plasma
membrane, enriched in cholesterol and glycosphingolipids, involved in regulation
of intracellular signaling. Among transcripts targeted by FMRP, a subset encodes
proteins involved in lipid biosynthesis and homeostasis, dysregulation of which
could affect the integrity and function of lipid rafts. Using a quantitative mass
spectrometry-based approach we analyzed the lipid raft proteome of Fmr1 knockout
mice, an animal model of Fragile X syndrome, and identified candidate proteins
that are differentially represented in Fmr1 knockout mice lipid rafts.
Furthermore, network analysis of these candidate proteins reveals connectivity
between them and predicts functional connectivity with genes encoding components
of myelin sheath, axonal processes and growth cones. Our findings provide insight
to aid identification of molecular and cellular dysfunctions arising from Fmr1
silencing and for uncovering shared pathologies between Fragile X syndrome and
other autism spectrum disorders.
PMID- 25849052
TI - The role of nailfold capillaroscopy in interstitial lung diseases - can it
differentiate idiopathic cases from collagen tissue disease associated
interstitial lung diseases?
AB - INTRODUCTION: Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test
that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We
aimed to evaluate whether NFC findings could be a clue for discriminating
idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD).
Additionally it was aimed to determine whether NFC could be helpful in
discriminating usual interstitial pneumonia (UIP) pattern from non-specific
interstitial pneumonia (NSIP) pattern. MATERIALS AND METHODS: We grouped patients
into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the
control group. The CTD-ILD group was split into two subgroups: 8 patients with
Sjogren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)
associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8
IPF patients. The control group consisted of 10 SJS and 7 RA patients without
lung disease. None of the patients were on acute exacerbation at the time of
examination, and none had Reynaud's phenomenon. RESULTS: Mean capillary density
was significantly reduced only in the CTD-ILD group as compared to the control
group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and
SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary
density in patients with the UIP pattern was reduced compared to patients with
the NSIP pattern and those in the control group; p values were 0.008 and < 0.001,
respectively. CONCLUSION: This study is to be the first describing and comparing
the nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC
findings can be helpful in discriminating UIP patterns from NSIP patterns. But to
show its role in differentiating idiopathic disease, more studies with more
patients are needed.
PMID- 25849053
TI - A new approach in the diagnosis of upper airway resistance syndrome (UARS): PAP
method.
AB - INTRODUCTION: Upper airway resistance syndrome (UARS) is characterized by
repeated number of arousals at night, and excessive daytime sleepiness or
somnolence (EDS). It is often missed in classical polysomnographic diagnostic
approaches and misdiagnosed as simple snoring or idiopathic hypersomnia, thereby
is often left untreated. We propose that positive airway pressure (PAP), which
has shown to be effective against UARS, can be used as a diagnostic tool as well.
The study designed to test whether patients with high titration pressures can be
diagnosed for UARS, and whether this pressure can be used as the treatment
pressure in UARS. MATERIALS AND METHODS: This study is a retrospective cohort
study. The patients with the following selection criteria: apnea hypopnea index
(AHI) < 5, respiratory effort related arousal (RERA) index > 20, excessive
daytime sleepiness or somnolence (EDS) without nocturnal oxygen desaturation
levels were included to the study. After diagnostic polysomnography (PSG), PAP
titrarion was applied to diagnose and treatment. RESULTS: Fourteen (%46.7) of the
patients were male, 16 (%53.3) were female, with a mean age of 46.4 +/- 9.9 and
mean body mass index (BMI) of 26 +/- 3.3. The patiens had a mean Epworth
sleepiness scale 15.3 +/- 3.9, mean AHI: 2.3 +/- 1.4 and average RERA: 26.1 +/-
4.9. The mean CPAP titration pressure was 7.1 +/- 1.1 cmH2O. CONCLUSION: In the
light of current findings, during PAP titration patients required high pressures
is the evidence of increased upper airway resistance in UARS. Using the from
therapy to diagnosis protocol, the PAP protocol determines the individual
therapeutic pressures needed by patients. Following up the clinical outcomes of
these patients under the PAP treatment, and including a larger cohort will
contribute greatly to treating this syndrome, defined as one of the "unresolved
problems in years".
PMID- 25849054
TI - A rarely seen diffuse parenchymal lung disease: diffuse pulmonary
meningotheliomatosis.
AB - Pulmonary meningothelial-like nodules (MLNs) are usually detected incidentally
during pathologic evaluation of resected pulmonary parenchymal specimens and
autopsies. These nodules are generally asymptomatic and most often single.
Diffuse pulmonary involvement by MLNs is less frequently described. MLNs are
benign lesions and have been associated with neoplastic and non-neoplastic
pulmonary conditions and occasionally with extrapulmonary diseases. We report a
case of a female patient presenting with multiple and bilateral pulmonary nodules
diagnosed with "diffuse pulmonary meningotheliomatosis" by video-assisted
thoracoscopic surgery (VATS). Diffuse pulmonary meningotheliomatosis should be
included in the differential diagnosis of diffuse bilateral lung nodules in the
radiologic studies.
PMID- 25849055
TI - [Sedation for fiberoptic bronchoscopy: review of the literature].
AB - Fiberoptic bronchoscopy (FOB) is a procedure which has an important role in the
diagnosis and treatment of lung diseases and is widely used in clinical practice.
It is an invasive procedure and can cause cough, shortness of breath, nose and
throat irritation. Stress during bronchoscopy can cause release of
catecholamines, which may lead to tachycardia, vasoconstriction and possible
myocardial ischemia in patients with impaired cardiopulmonary function. Current
guidelines for bronchoscopy recommend offering sedation to patients, with the aim
of improving patient comfort and reducing complications. For this purpose, the
most frequently used sedatives are benzodiazepines, opioids, propofol and
fospropofol which are either administered alone or in combination. In this
review, we aimed to evaluate various drugs used for sedation during bronchoscopy.
PMID- 25849056
TI - [A newly-defined entity: combined pulmonary fibrosis and emphysema syndrome].
AB - Combined pulmonary fibrosis and emphysema (CPFE) syndrome is a rare disease
characterized with shortness of breath, upper lobe emphysema, lower lobe fibrosis
and impairment of gas exchange. This syndrome is a disease usually seen in male
smokers. Pulmonary hypertension is associated with mortality. Another important
feature, spirometric volumes relatively protected and a reduction in carbon
monoxide diffusion test. CPFE syndrome in the literature so far have been
identified in only 70 patients. In this review CPFE syndrome is presented with
literature.
PMID- 25849057
TI - Perioperative evaluation for the patients with obstructive sleep apnea syndrome.
AB - Obstructive sleep apnea syndrome, that has been more frequently diagnosed lately
and whose importance has been gradually understood better, is a widespread health
problem. This syndrome has been accompanied by obesity frequently. In the
obstructive sleep apnea syndrome, it has been known that hypoxia and sometimes
hypercarbia additionally has been observed, nevertheless cardiovascular problems
have been observed more frequently in the aforementioned patient group in
comparison with other individuals. Anesthetic substituents applied during the
invasive operations and some medicine used for analgesia may cause the increase
of the aforesaid hypoxia and cardiovascular problems in the obstructive sleep
apnea syndrome. Nowadays, with the improvements in accessing to health agencies
and consequently with the increase in the number of surgical applications, this
review has been prepared with the thought of helping to clinicians about the
approach and the pre-anesthetic and post-anesthetic precautions required to be
taken within the mentioned patient group.
PMID- 25849058
TI - The value of endotracheal aspirate culture in newborn infants with ventilator
associated pneumonia.
PMID- 25849059
TI - A rare cause of bronchiectasis.
PMID- 25849060
TI - Bochdalek hernia in a middle-aged man.
PMID- 25849061
TI - A rare case of recurrent pneumonia: FMF.
PMID- 25849062
TI - Images of Place: Visuals from Migrant Women Sex Workers in South Africa.
AB - Many migrants in inner-city Johannesburg survive through unconventional and
sometimes criminalized livelihood activities. In this article, we draw on data
from a study that applied a participatory visual methodology to work with migrant
women who sell sex, and explored the suitability of this approach as a way to
engage with a presumed 'hard to reach' urban population. The lived experiences of
migrant women sex workers were documented by combining participatory visual
methods with a more traditional ethnographic approach, and this approach led us
to new ways of seeing their worlds. This methodological approach raises important
considerations for working with marginalized and criminalized urban groups.
PMID- 25849063
TI - Strategies for research recruitment and retention of older adults of racial and
ethnic minorities.
AB - HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS 1.4 contact
hours will be awarded by Villanova University College of Nursing upon successful
completion of this activity. A contact hour is a unit of measurement that denotes
60 minutes of an organized learning activity. This is a learner-based activity.
Villanova University College of Nursing does not require submission of your
answers to the quiz. A contact hour certificate will be awarded once you
register, pay the registration fee, and complete the evaluation form online at
http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article,
"Strategies for Research Recruitment and Retention of Older Adults of Racial and
Ethnic Minorities" found on pages 14-23, carefully noting any tables and other
illustrative materials that are included to enhance your knowledge and
understanding of the content. Be sure to keep track of the amount of time (number
of minutes) you spend reading the article and completing the quiz. 2. Read and
answer each question on the quiz. After completing all of the questions, compare
your answers to those provided within this issue. If you have incorrect answers,
return to the article for further study. 3. Go to the Villanova website listed
above to register for contact hour credit. You will be asked to provide your
name; contact information; and a VISA, MasterCard, or Discover card number for
payment of the $20.00 fee. Once you complete the online evaluation, a certificate
will be automatically generated. This activity is valid for continuing education
credit until April 30, 2018. CONTACT HOURS This activity is co-provided by
Villanova University College of Nursing and SLACK Incorporated. Villanova
University College of Nursing is accredited as a provider of continuing nursing
education by the American Nurses Credentialing Center's Commission on
Accreditation. ACTIVITY OBJECTIVE 1. Identify strategies and barriers for the
recruitment and retention of older adults of racial and ethnic minorities in
cognitive aging research. DISCLOSURE STATEMENT Neither the planners nor the
authors have any conflicts of interest to disclose. The numbers of Hispanic and
African American older adults in the United States are expected to increase by
86% and more than 31%, respectively. African American and Hispanic American
individuals are more likely than Caucasian individuals to have chronic health
conditions, and researchers have argued that these health disparities may
contribute to their higher rates of dementia-related illnesses. The current
article explores strategies to improve participation in cognitive aging research
by older adults, particularly minority older adults. The cultural aspects of
cognitive aging are examined, especially the role of stigma and stereotype
threat. The perceptions of cognitive aging of African American and Hispanic older
adults are also described. Specific strategies are presented that have been
successfully implemented to improve recruitment and retention in research
targeting minority older adults. Strategies that yielded retention of minority
older adults included advertising and marketing a randomized clinical trial,
media relations, intervention tailoring, and adaptation of psychometric
instruments.
PMID- 25849064
TI - The Correlation of Social Support and Social Participation of Older Adults in
Bandar Abbas, Iran.
AB - Social participation is a criterion for successful aging. Research has shown that
social participation decreases in older adults. However, the role of social
support on older adults' social participation has received little attention,
especially in eastern countries, such as Iran. Using the Social Participation
Questionnaire, the relationship between social support and social participation
was investigated in 525 Iranian older adults. A correlation was found between
social support and social participation of older adults. Older adult women were
found to have less social support and social participation compared with men.
PMID- 25849066
TI - Efficient coupling of nanoparticles to electrochemically exfoliated graphene.
AB - Electrochemically exfoliated graphene (EEG) is a new generation of high-quality
graphene that holds great promise for the construction of hybrid materials.
However, the assembly of EEG hybrids with well-defined nanostructures has
remained a major challenge. In this study, we demonstrate a bottom-up approach
toward the assembly of EEG sheets with a series of functional nanoparticles (Si,
Fe3O4, and Pt NPs) into two-dimensional sandwich-like hybrid nanostructures.
Polyaniline in the emeraldine base form functions as a versatile dopant to couple
NPs onto EEG through either electrostatic interactions or hydrogen bonding. This
protocol enables processing and assembly of EEG using an economical pathway, for
which we further demonstrate the potential application of EEG-Si hybrids as high
performance anode material for lithium storage.
PMID- 25849065
TI - Protective Effect of Super-Critical Carbon Dioxide Fluid Extract from Flowers and
Buds of Chrysanthemum indicum Linnen Against Ultraviolet-Induced Photo-Aging in
Mice.
AB - It is known that solar ultraviolet (UV) radiation to human skin causes photo
aging, including increases in skin thickness and wrinkle formation and reduction
in skin elasticity. UV radiation induces damage to skin mainly by superfluous
reactive oxygen species and chronic low-grade inflammation, which eventually up
regulate the expression of matrix metalloproteinases (MMPs). In this study, the
super-critical carbon dioxide extract from flowers and buds of Chrysanthemum
indicum Linnen (CISCFE), which has been reported to possess free radical
scavenging and anti-inflammatory properties, was investigated for its photo
protective effect by topical application on the skin of mice. Moreover, CISCFE
effectively suppressed the UV-induced increase in skin thickness and wrinkle
grading in a dose-dependent manner, which was correlated with the inhibition of
loss of collagen fiber content and epidermal thickening. Furthermore, we observed
that CISCFE could obviously decrease UV-induced skin inflammation by inhibiting
the production of inflammatory cytokines (interleukin-1beta [IL-1beta, IL-6, IL
10, tumor necrosis factor-alpha), alleviate the abnormal changes of anti
oxidative indicators (superoxide dismutase, catalase, and glutathione
peroxidase), and down-regulate the levels of MMP-1 and MMP-3. The results
indicated that CISCFE was a novel photo-protective agent from natural resources
against UV irradiation.
PMID- 25849067
TI - NexGenEx-Tom: a gene expression platform to investigate the functionalities of
the tomato genome.
AB - BACKGROUND: Next Generation Sequencing technologies (NGS) unexpectedly pushed
forward the capability of solving genome organization and of widely depicting
gene expression. However, although the flourishing of tools to process the NGS
data, versatile and user-friendly computational environments for integrative and
comparative analyses of the results from the increasing amount of collections are
still required. DESCRIPTION: Here we present the architecture and the facilities
of NexGenEx-, a web based platform that offers processed NGS transcriptome
collections and enables immediate analyses of the results. The platform allows
gene expression investigations, profiling and comparisons, and exploits different
resources. CONCLUSION: In the current version, NexGenEx-Tom includes processed
and normalized NGS expression data from three collections covering several
tissue/stages from different genotypes. Beyond providing a user-friendly
interface, the platform was designed with the aim to easily be expanded to
include other NGS based transcriptome collections. It can also integrate
different genome releases, possibly from different cultivars or genotypes, but
even from different species. The platform is proposed as an example effort in
tomato, and is described as a profitable approach for the exploitation of these
challenging and precious datasets.
PMID- 25849068
TI - A Comparative Study Between the Wingate and Force-Velocity Anaerobic Cycling
Tests: Effect of Physical Fitness.
AB - PURPOSE: To verify the hypothesis that the peak power (PP) of a Wingate test (WT)
is an underestimation of maximal power (P(max)) computed from the force-velocity
test (FVT), to examine possible fatigue effect on P(max), and to investigate the
effect of load on mean power (MP) and fatigue index (FI) during a WT in trained
and recreational men. METHODS: Ten recreational (22.9 +/- 1.7 y, 1.81 +/- 0.06 m,
73.3 +/- 10.4 kg) and 10 highly trained subjects (22.7 +/- 1.4 y, 1.85 +/- 0.05
m, 78.9 +/- 6.6 kg) performed 2 WTs with 2 loads (8.7% and 11% of body mass [BM])
and an FVT on the same cycle ergometer, in randomized order. RESULTS: Optimal
load was equal to 10% BM in recreational participants. Given the quadratic
relationship between load and power, the underestimation of P(max) was lower than
10% for the average values of trained and recreational participants with both
loads. However, PP with a load equal to 8.7% BM was a large underestimation
(~30%) of P(max) in the most powerful individuals. In addition, PP was not
greater than P(max) of FVT for the same load. FI was independent of the load only
if it was expressed relative to PP. The optimal load for MP during WT was close
to the optimal load for PP. CONCLUSIONS: The optimal load for WT performance
should be approximately equal to 10% BM in recreational subjects. In powerful
subjects, the FVT appears to be more appropriate in assessing maximal power, and
loads higher than 11% BM should be verified for the WT.
PMID- 25849069
TI - Cigarette smoke inhibits BAFF expression and mucosal immunoglobulin A responses
in the lung during influenza virus infection.
AB - BACKGROUND: It is incompletely understood how cigarette smoke (CS) exposure
affects lung mucosal immune responses during viral respiratory infections. B cell
activating factor belonging to the tumor necrosis factor family (BAFF) plays an
important role in the induction of secretory immunoglobulin A (S-IgA) which is
the main effector of the mucosal immune system. We therefore investigated the
effects of CS exposure on BAFF expression and S-IgA responses in the lung during
influenza virus infection. METHODS: Mice were exposed to CS and/or infected with
influenza virus. Bronchoalveolar lavage fluid and lung compartments were analyzed
for BAFF expression, influenza-specific S-IgA level and histological changes.
Lung B cells were isolated and the activation-induced cytidine deaminase (Aicda)
expression was determined. BEAS-2B cells were treated with CS extract (CSE),
influenza virus, interferon beta or N-acetylcysteine and BAFF expression was
measured. RESULTS: CS inhibited BAFF expression in the lung, particularly after
long-term exposure. BAFF and S-IgA levels were increased during influenza virus
infection. Three-month CS exposure prior to influenza virus infection resulted in
reduced BAFF and S-IgA levels in the lung as well as augmented pulmonary
inflammation on day 7 after infection. Prior CS exposure also caused decreased
Aicda expression in lung B cells during infection. Neutralization of BAFF in the
lung resulted in reduced S-IgA levels during influenza virus infection. CSE
inhibited virus-mediated BAFF induction in a dose-dependent manner in BEAS-2B
cells, while this inhibition of BAFF by CSE was prevented by pretreatment with
the antioxidant N-acetylcysteine. CONCLUSIONS: Our findings indicate that CS may
hinder early mucosal IgA responses in the lung during influenza virus infection
through oxidative inhibition of BAFF, which might contribute to the increased
incidence and severity of viral infections in smokers.
PMID- 25849070
TI - Herbal medicines and chemotherapy induced peripheral neuropathy (CIPN): A
critical literature review.
AB - BACKGROUND: Chemotherapy induced peripheral neuropathy [CIPN] is a common
significant and debilitating side-effect resulting from the administration of
neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include
taxanes, vinca alkaloids, platinum analogues, and others. Moderate to severe CIPN
significantly decreases the quality of life and physical abilities of cancer
patients and current pharmacotherapy for CIPN e.g. Amifostine, and
antidepressants have had limited efficacy and may themselves induce adverse side
effects. METHODS: To determine the potential use of herbal medicines as adjuvants
in cancer treatments, a critical literature review was conducted by electronic
and manual search on nine databases. These include PubMed, the Cochrane Library,
Science Direct, Scopus, EMBASE, MEDLINE, Google Scholar, and two Chinese
databases CNKI and CINAHL. Thirty-four studies were selected from 5614 studies
assessed and comprising animal studies, case reports, retrospective studies, and
minimal randomized clinical trials investigating the anti-CIPN effect of herbal
medicines as the adjuvant intervention in patients administered chemotherapy. The
thirty-four studies were assessed on methodological quality and limitations
identified. RESULTS: Studies were mixed in their recommendations for herbal
medicines as an adjuvant treatment for CIPN. CONCLUSION: Currently no agent has
shown solid beneficial evidence to be recommended for the treatment or
prophylaxis of CIPN. Given that the number of cancer survivors is increasing, the
long-term side effects of cancer treatment, is of major importance.
PMID- 25849071
TI - Hidden voices: prevalence and risk factors for violence against women with
disabilities in Nepal.
AB - BACKGROUND: There is an increasing body of evidence on the extent and predictors
of violence against women in Nepal. However, much of the published research does
not yet take into account additional features of marginalization and
vulnerability suffered by some women - for example, women socially excluded on
account of their disability. Critical gaps exist in empirical data on the extent,
risk factors, access to care, socio-economic and health consequences of violence
among women with disabilities in Nepal. This paper addresses some these gaps and
aims to promote evidence-informed policy and programme responses in Nepal.
METHODS: We conducted a cross-sectional survey of 475 women with disability aged
16 years and above in three districts in Nepal. In-depth interviews with 12 women
who reported violence in the survey were also carried out. Using multivariate
statistical methods we estimated the prevalence and risk factors for violence
experienced both over the past 12 months and lifetime. RESULTS: Over the
lifetime, 57.7% of women reported they had ever experienced violence, including
emotional violence (55.2%); physical violence (34%); and sexual violence (21.5%).
Over the preceding 12 months, 42% of women reported that they had experienced
violence. Multivariate analysis showed that women with disabilities who were
young, working in paid employment, and those who required permission from
husbands/family to go to health centres or participate in community organizations
were at increased risk of violence. Women experienced a range of negative
outcomes from violence - including physical and emotional trauma. However, a
majority of women did not seek care or redress from the health, justice or other
sectors. CONCLUSIONS: Women in Nepal are at high risk of violence, often from
members of their immediate family or local community. Rates of violence are
higher in women with disability than among women in the general population.
Tackling violence requires a comprehensive approach that addresses the root
causes of women's unequal position in society, and builds upon principles of
equity and justice to ensure that all women are able to realize their rights to a
life free from violence.
PMID- 25849073
TI - Structural features of Sm- and Gd-doped ceria studied by synchrotron X-ray
diffraction and MU-Raman spectroscopy.
AB - A structural study of Sm- and Gd-doped ceria was performed with the aim to
clarify some unexplained structural features. (Ce1-xREx)O2-x/2 samples (RE = Sm,
Gd; x = 0, 0.1, ..., 1) were prepared by coprecipitation of mixed oxalates and
subsequent thermal treatment at 1473, 1173, or 1073 K in air; they were then
analyzed at room temperature both by synchrotron X-ray diffraction and MU-Raman
spectroscopy. Two structural models were adopted to fit the experimental data,
namely, a fluoritic one, resembling the CeO2 structure at low RE content, and a
hybrid one at higher RE content, intermediate between the CeO2 and the RE2O3
structures. Two main transitions were detected along the compositional range: (a)
an RE-dependent transition at the boundary between the fluoritic and the hybrid
regions, of a chemical nature; (b) an RE-independent transition within the hybrid
region at ~0.5, having a purely geometrical nature. The presence of two finely
interlaced F- and C-based structures within the hybrid region was confirmed, and
hints of their composition were obtained by MU-Raman spectroscopy. The obtained
results indicate a possible explanation for the non-Vegard behavioral trend of
the cell parameters.
PMID- 25849072
TI - Effective immuno-targeting of the IDH1 mutation R132H in a murine model of
intracranial glioma.
AB - The R132H mutation of cytosolic isocitrate dehydrogenase (IDH1) is present in the
majority of low grade gliomas.Immunotherapy in these tumors has an interesting,
still unexploited, therapeutic potential, as they are less immunosuppressive than
glioblastomas. Using site-directed mutagenesis we introduced the R132H mutation
into the murine glioma cell line GL261,creating mIDH1-GL261. Presence of the
mutation was confirmed by immunoblotting and production of the oncometabolite 2
hydroxyglutarate (2HG), demonstrated by mass spectrometry (LC-MS/MS) performed on
cell supernatant. In vitro mIDH1-GL261 had different morphology but similar
growth rate than parental GL261 (p-GL261). After intracranial injection, MRI
suggested that the initial growth rate was slower in mIDH1-GL261 than p-GL261
gliomas but overall survival was similar. mIDH1-GL261 gliomas showed evidence of
R132H expression and of intratumoral 2HG production (evaluated by MRS and LC
MS/MS). Immunizations were performed nine days after intracranial implantation of
mIDH1- or p-GL261 cells by three subcutaneous injections of five different
peptides encompassing the IDH1 mutation site, all emulsified with Montanide ISA
51, in association with GM-CSF. Control mice were injected with four ovalbumin
peptides or vehicle. Mice with mIDH1-GL261 but not p-GL261 gliomas treated with
mIDH1 peptides survived longer than controls; 25% of them were cured. Immunized
mice showed higher amounts of peripheral CD8+ T cells, higher production of IFN
gamma, and evidence of anti-mIDH1 antibodies.Immunizations led to intratumoral up
regulation of IFN-gamma, granzyme-b and perforin-1 and down-regulation of TGF
beta2 and IL-10. These results support the translational potential of
immunotherapeutic targeting of gliomas carrying IDH1 mutations.
PMID- 25849074
TI - In vivo compatibility of graphene oxide with differing oxidation states.
AB - Graphene oxide (GO) is suggested to have great potential as a component of
biomedical devices. Although this nanomaterial has been demonstrated to be
cytocompatible in vitro, its compatibility in vivo in tissue sites relevant for
biomedical device application is yet to be fully understood. Here, we evaluate
the compatibility of GO with two different oxidation levels following
implantation in subcutaneous and intraperitoneal tissue sites, which are of broad
relevance for application to medical devices. We demonstrate GO to be moderately
compatible in vivo in both tissue sites, with the inflammatory reaction in
response to implantation consistent with a typical foreign body reaction. A
reduction in the degree of GO oxidation results in faster immune cell
infiltration, uptake, and clearance following both subcutaneous and peritoneal
implantation. Future work toward surface modification or coating strategies could
be useful to reduce the inflammatory response and improve compatibility of GO as
a component of medical devices.
PMID- 25849075
TI - Protein palmitoylation is critical for the polar growth of root hairs in
Arabidopsis.
AB - BACKGROUND: Protein palmitoylation, which is critical for membrane association
and subcellular targeting of many signaling proteins, is catalyzed mainly by
protein S-acyl transferases (PATs). Only a few plant proteins have been
experimentally verified to be subject to palmitoylation, such as ROP GTPases,
calcineurin B like proteins (CBLs), and subunits of heterotrimeric G proteins.
However, emerging evidence from palmitoyl proteomics hinted that protein
palmitoylation as a post-translational modification might be widespread.
Nonetheless, due to the large number of genes encoding PATs and the lack of
consensus motifs for palmitoylation, progress on the roles of protein
palmitoylation in plants has been slow. RESULTS: We combined pharmacological and
genetic approaches to examine the role of protein palmitoylation in root hair
growth. Multiple PATs from different endomembrane compartments may participate in
root hair growth, among which the Golgi-localized PAT24/TIP GROWTH DEFECTIVE1
(TIP1) plays a major role while the tonoplast-localized PAT10 plays a secondary
role in root hair growth. A specific inhibitor for protein palmitoylation, 2
bromopalmitate (2-BP), compromised root hair elongation and polarity. Using
various probes specific for cellular processes, we demonstrated that 2-BP
impaired the dynamic polymerization of actin microfilaments (MF), the asymmetric
plasma membrane (PM) localization of phosphatidylinositol (4,5)-bisphosphate
(PIP2), the dynamic distribution of RabA4b-positive post-Golgi secretion, and
endocytic trafficking in root hairs. CONCLUSIONS: By combining pharmacological
and genetic approaches and using root hairs as a model, we show that protein
palmitoylation, regulated by protein S-acyl transferases at different
endomembrane compartments such as the Golgi and the vacuole, is critical for the
polar growth of root hairs in Arabidopsis. Inhibition of protein palmitoylation
by 2-BP disturbed key intracellular activities in root hairs. Although some of
these effects are likely indirect, the cytological data reported here will
contribute to a deep understanding of protein palmitoylation during tip growth in
plants.
PMID- 25849076
TI - A nontoxic polypeptide oligomer with a fungicide potency under agricultural
conditions which is equal or greater than that of their chemical counterparts.
AB - There are literally hundreds of polypeptides described in the literature which
exhibit fungicide activity. Tens of them have had attempted protection by patent
applications but none, as far as we are aware, have found application under real
agricultural conditions. The reasons behind may be multiple where the sensitivity
to the Sun UV radiation can come in first place. Here we describe a
multifunctional glyco-oligomer with 210 kDa which is mainly composed by a 20 kDa
polypeptide termed Blad that has been previously shown to be a stable
intermediary product of beta-conglutin catabolism. This oligomer accumulates
exclusively in the cotyledons of Lupinus species, between days 4 and 12 after the
onset of germination. Blad-oligomer reveals a plethora of biochemical properties,
like lectin and catalytic activities, which are not unusual per si, but are
remarkable when found to coexist in the same protein molecule. With this vast
range of chemical characteristics, antifungal activity arises almost as a natural
consequence. The biological significance and potential technological applications
of Blad-oligomer as a plant fungicide to agriculture, its uniqueness stems from
being of polypeptidic in nature, and with efficacies which are either equal or
greater than the top fungicides currently in the market are addressed.
PMID- 25849077
TI - Control of rhGH Release Profile from PEG-PAF Thermogel.
AB - Poly(ethylene glycol)-poly(l-alanine-co-l-phenyl alanine) diblock copolymers (PEG
PAF) of 2000-990 Da (P2K) and 5000-2530 Da (P5K) with the different molecular
weights of PEGs, but having a similar molecular weight ratio of hydrophobic block
to hydrophilic block were synthesized to compare their solution behavior and
corresponding protein drug release profiles from their in situ formed thermogels.
The PEG-PAF aqueous solutions underwent heat-induced sol-to-gel transition in a
concentration range of 18.0-24.0 wt % and 8.0-12.0 wt % for P2K and P5K,
respectively. P5K formed bigger micelles than P2K, of a broad distribution,
whereas the PAF blocks of P5K developed richer in alpha-helix than those of P2K
in the core of the micelles. As the temperature increased, the micelles underwent
dehydration of the PEG, which led to the aggregation of micelles, while the
secondary structure of PAF was slightly affected during the sol-to-gel
transition. The P5K exhibited higher tendency to aggregate and formed a tighter
gel than P2K. Upon injection into the subcutaneous layer of rats, both polymer
aqueous solutions formed a biocompatible gel with typical mild inflammatory
tissue responses. Recombinant human growth hormone (rhGH) maintained its
stability without forming any aggregates in both sol (4 degrees C) and gel (37
degrees C) states of the PEG-PAFs. Even though P2K and P5K have a similar
molecular weight ratio of hydrophobic block to hydrophilic block, the P5K system
exhibited a reduced initial burst release, improved bioavailability, and
prolonged therapeutic duration of the rhGH, compared to the P2K system. The
current research suggests that a drug release profile is a complex function of
self-assembling carriers and incorporated drugs, and thus, a promising protein
delivery system could be designed by adjusting the molecular parameters of a
thermogel.
PMID- 25849078
TI - RNA-mediated degradation of microRNAs: A widespread viral strategy?
AB - Regulation of small RNAs by other non-coding RNAs is a ubiquitous feature of gene
regulatory systems that can be exploited by viruses. Examples of this have been
described in 3 different herpesviruses, where viral non-coding RNAs bind to
highly abundant cellular (miRNAs), mediating their degradation: miR-27 is
targeted by both murine cytomegalovirus and herpesvirus saimiri, while the miR-17
family is targeted by human cytomegalovirus. We review what is known about RNA
mediated regulation of miRNA stability and propose 3 potential roles that viral
non-coding RNAs might assume to initiate the destruction of a miRNA, acting as
"recruiters," "localizers" or "exposers." Whereas the miRNAs (miR-17 and miR-27)
appear to be ancient and pre-date the common ancestor of all mammalian
herpesviruses, comparative analyses of herpesvirus genomes indicate that the 3
known viral regulators of miRNA each evolved independently, and much more
recently. Noting that the anti-viral activity of miRNAs might be countered by a
variety of mechanisms, we propose that (i) there has been continual turnover of
these mechanisms during herpesvirus evolution, and (ii) there may be many other,
as yet undescribed, anti-miRNA activities encoded by other herpesviruses and
indeed by viruses from other families.
PMID- 25849079
TI - The transcriptome signature of the receptive bovine uterus determined at early
gestation.
AB - Pregnancy success is critical to the profitability of cattle operations. However,
the molecular events driving the uterine tissue towards embryo receptivity are
poorly understood. This study aimed to characterize the uterine transcriptome
profiles of pregnant (P) versus non-pregnant (NP) cows during early pregnancy and
attempted to define a potential set of marker genes that can be valuable for
predicting pregnancy outcome. Therefore, beef cows were synchronized (n=51) and
artificially inseminated (n=36) at detected estrus. Six days after AI (D6),
jugular blood samples and a biopsy from the uterine horn contralateral to the
ovary containing the corpus luteum were collected. Based on pregnancy outcome on
D30, samples were retrospectively allocated to the following groups: P (n=6) and
NP (n=5). Both groups had similar plasma progesterone concentrations on D6.
Uterine biopsies were submitted to RNA-Seq analysis in a Illumina platform. The
272,685,768 million filtered reads were mapped to the Bos Taurus reference genome
and 14,654 genes were analyzed for differential expression between groups.
Transcriptome data showed that 216 genes are differently expressed when comparing
NP versus P uterine tissue (Padj <= 0.1). More specifically, 36 genes were up
regulated in P cows and 180 are up-regulated in NP cows. Functional enrichment
and pathway analyses revealed enriched expression of genes associated with
extracellular matrix remodeling in the NP cows and nucleotide binding, microsome
and vesicular fraction in the P cows. From the 40 top-ranked genes, the
transcript levels of nine genes were re-evaluated using qRT-PCR. In conclusion,
this study characterized a unique set of genes, expressed in the uterus 6 days
after insemination, that indicate a receptive state leading to pregnancy success.
Furthermore, expression of such genes can be used as potential markers to
efficiently predict pregnancy success.
PMID- 25849080
TI - Unique honey bee (Apis mellifera) hive component-based communities as detected by
a hybrid of phospholipid fatty-acid and fatty-acid methyl ester analyses.
AB - Microbial communities (microbiomes) are associated with almost all metazoans,
including the honey bee Apis mellifera. Honey bees are social insects,
maintaining complex hive systems composed of a variety of integral components
including bees, comb, propolis, honey, and stored pollen. Given that the
different components within hives can be physically separated and are
nutritionally variable, we hypothesize that unique microbial communities may
occur within the different microenvironments of honey bee colonies. To explore
this hypothesis and to provide further insights into the microbiome of honey
bees, we use a hybrid of fatty acid methyl ester (FAME) and phospholipid-derived
fatty acid (PLFA) analysis to produce broad, lipid-based microbial community
profiles of stored pollen, adults, pupae, honey, empty comb, and propolis for 11
honey bee hives. Averaging component lipid profiles by hive, we show that, in
decreasing order, lipid markers representing fungi, Gram-negative bacteria, and
Gram-positive bacteria have the highest relative abundances within honey bee
colonies. Our lipid profiles reveal the presence of viable microbial communities
in each of the six hive components sampled, with overall microbial community
richness varying from lowest to highest in honey, comb, pupae, pollen, adults and
propolis, respectively. Finally, microbial community lipid profiles were more
similar when compared by component than by hive, location, or sampling year.
Specifically, we found that individual hive components typically exhibited
several dominant lipids and that these dominant lipids differ between components.
Principal component and two-way clustering analyses both support significant
grouping of lipids by hive component. Our findings indicate that in addition to
the microbial communities present in individual workers, honey bee hives have
resident microbial communities associated with different colony components.
PMID- 25849081
TI - Reduced Tyk2 gene expression in beta-cells due to natural mutation determines
susceptibility to virus-induced diabetes.
AB - Accumulating evidence suggests that viruses play an important role in the
development of diabetes. Although the diabetogenic encephalomyocarditis strain D
virus induces diabetes in restricted lines of inbred mice, the susceptibility
genes to virus-induced diabetes have not been identified. We report here that
novel Tyrosine kinase 2 (Tyk2) gene mutations are present in virus-induced
diabetes-sensitive SJL and SWR mice. Mice carrying the mutant Tyk2 gene on the
virus-resistant C57BL/6 background are highly sensitive to virus-induced
diabetes. Tyk2 gene expression is strongly reduced in Tyk2-mutant mice,
associated with low Tyk2 promoter activity, and leads to decreased expression of
interferon-inducible genes, resulting in significantly compromised antiviral
response. Tyk2-mutant pancreatic beta-cells are unresponsive even to high dose of
Type I interferon. Reversal of virus-induced diabetes could be achieved by beta
cell-specific Tyk2 gene expression. Thus, reduced Tyk2 gene expression in
pancreatic beta-cells due to natural mutation is responsible for susceptibility
to virus-induced diabetes.
PMID- 25849082
TI - Genetic mapping of QTLs controlling fatty acids provided insights into the
genetic control of fatty acid synthesis pathway in peanut (Arachis hypogaea L.).
AB - Peanut, a high-oil crop with about 50% oil content, is either crushed for oil or
used as edible products. Fatty acid composition determines the oil quality which
has high relevance to consumer health, flavor, and shelf life of commercial
products. In addition to the major fatty acids, oleic acid (C18:1) and linoleic
acid (C18:2) accounting for about 80% of peanut oil, the six other fatty acids
namely palmitic acid (C16:0), stearic acid (C18:0), arachidic acid (C20:0),
gadoleic acid (C20:1), behenic acid (C22:0), and lignoceric acid (C24:0) are
accounted for the rest 20%. To determine the genetic basis and to improve further
understanding on effect of FAD2 genes on these fatty acids, two recombinant
inbred line (RIL) populations namely S-population (high oleic line 'SunOleic 97R'
* low oleic line 'NC94022') and T-population (normal oleic line 'Tifrunner' * low
oleic line 'GT-C20') were developed. Genetic maps with 206 and 378 marker loci
for the S- and the T-population, respectively were used for quantitative trait
locus (QTL) analysis. As a result, a total of 164 main-effect (M-QTLs) and 27
epistatic (E-QTLs) QTLs associated with the minor fatty acids were identified
with 0.16% to 40.56% phenotypic variation explained (PVE). Thirty four major QTLs
(>10% of PVE) mapped on five linkage groups and 28 clusters containing more than
three QTLs were also identified. These results suggest that the major QTLs with
large additive effects would play an important role in controlling composition of
these minor fatty acids in addition to the oleic and linoleic acids in peanut
oil. The interrelationship among these fatty acids should be considered while
breeding for improved peanut genotypes with good oil quality and desired fatty
acid composition.
PMID- 25849084
TI - Surface tension of supercooled water determined by using a counterpressure
capillary rise method.
AB - Measurements of the surface tension of supercooled water down to -25 degrees C
have been reported recently (Hruby et al. J. Phys. Chem. Lett. 2014, 5, 425-428).
These experiments did not show any anomalous temperature dependence of the
surface tension of supercooled water reported by some earlier measurements and
molecular simulations. In the present work, this finding is confirmed using a
counterpressure capillary rise method (the counterpressure method) as well as
through the use of the classical capillary rise method (the height method). In
the counterpressure method, the liquid meniscus inside the vertical capillary
tube was kept at a fixed position with an in-house developed helium distribution
setup. A preset counterpressure was applied to the liquid meniscus when its
temperature changed from a reference temperature (30 degrees C) to the
temperature of interest. The magnitude of the counterpressure was adjusted such
that the meniscus remained at the same height, thus compensating the change of
the surface tension. One advantage of the counterpressure method over the height
method consists of avoiding the uncertainty due to a possible variation of the
capillary diameter along its length. A second advantage is that the equilibration
time due to the capillary flow of the highly viscous supercooled water can be
shortened. For both the counterpressure method and the height method, the actual
results are relative values of surface tension with respect to the surface
tension of water at the reference temperature. The combined relative standard
uncertainty of the relative surface tensions is less than or equal to 0.18%. The
new data between -26 and +30 degrees C lie close to the IAPWS correlation for
the surface tension of ordinary water extrapolated below 0.01 degrees C and do
not exhibit any anomalous features.
PMID- 25849083
TI - Delineating species with DNA barcodes: a case of taxon dependent method
performance in moths.
AB - The accelerating loss of biodiversity has created a need for more effective ways
to discover species. Novel algorithmic approaches for analyzing sequence data
combined with rapidly expanding DNA barcode libraries provide a potential
solution. While several analytical methods are available for the delineation of
operational taxonomic units (OTUs), few studies have compared their performance.
This study compares the performance of one morphology-based and four DNA-based
(BIN, parsimony networks, ABGD, GMYC) methods on two groups of gelechioid moths.
It examines 92 species of Finnish Gelechiinae and 103 species of Australian
Elachistinae which were delineated by traditional taxonomy. The results reveal a
striking difference in performance between the two taxa with all four DNA-based
methods. OTU counts in the Elachistinae showed a wider range and a relatively low
(ca. 65%) OTU match with reference species while OTU counts were more congruent
and performance was higher (ca. 90%) in the Gelechiinae. Performance rose when
only monophyletic species were compared, but the taxon-dependence remained. None
of the DNA-based methods produced a correct match with non-monophyletic species,
but singletons were handled well. A simulated test of morphospecies-grouping
performed very poorly in revealing taxon diversity in these small, dull-colored
moths. Despite the strong performance of analyses based on DNA barcodes, species
delineated using single-locus mtDNA data are best viewed as OTUs that require
validation by subsequent integrative taxonomic work.
PMID- 25849085
TI - Spectroscopic Characterization of Structural Changes in Membrane Scaffold
Proteins Entrapped within Mesoporous Silica Gel Monoliths.
AB - The changes in the orientation and conformation of three different membrane
scaffold proteins (MSPs) upon entrapment in sol-gel-derived mesoporous silica
monoliths were investigated. MSPs were examined in either a lipid-free or a lipid
bound conformation, where the proteins were associated with lipids to form
nanolipoprotein particles (NLPs). NLPs are water-soluble, disk-shaped patches of
a lipid bilayer that have amphiphilic MSPs shielding the hydrophobic lipid tails.
The NLPs in this work had an average thickness of 5 nm and diameters of 9.2, 9.7,
and 14.8 nm. We have previously demonstrated that NLPs are more suitable lipid
based structures for silica gel entrapment than liposomes because of their size
compatibility with the mesoporous network (2-50 nm) and minimally altered
structure after encapsulation. Here we further elaborate on that work by using a
variety of spectroscopic techniques to elucidate whether or not different MSPs
maintain their protein-lipid interactions after encapsulation. Fluorescence
spectroscopy and quenching of the tryptophan residues with acrylamide, 5-DOXYL
stearic acid, and 16-DOXYL-stearic acid were used to determine the MSP
orientation. We also utilized fluorescence anisotropy of tryptophans to measure
the relative size of the NLPs and MSP aggregates after entrapment. Finally,
circular dichroism spectroscopy was used to examine the secondary structure of
the MSPs. Our results showed that, after entrapment, all of the lipid-bound MSPs
maintained orientations that were minimally changed and indicative of association
with lipids in NLPs. The tryptophan residues appeared to remain buried within the
hydrophobic core of the lipid tails in the NLPs and appropriately spaced from the
bilayer center. Also, after entrapment, lipid-bound MSPs maintained a high degree
of alpha-helical content, a secondary structure associated with protein-lipid
interactions. These findings demonstrate that NLPs are capable of serving as
viable hosts for functional integral membrane proteins in the synthesis of sol
gel-derived bioinorganic hybrid nanomaterials.
PMID- 25849087
TI - Do hotter temperatures increase the incidence of self-harm hospitalisations?
AB - A relationship between air temperature and the incidence of suicide has been
established in a number of previous studies. Interestingly, the relationship
between geographical variation in temperature and suicide incidence has generally
been found to be negative, while the relationship between temporal variation in
temperature and suicide incidence has generally been found to be positive. It is
less clear, however, how temperature relates to the incidence of self-harm. This
topic is of particular importance given the presence of ongoing global warming.
This study investigated the relationship between temperature and the incidence of
self-harm resulting in hospitalisation in New Zealand. Self-harm hospitalisations
by date and district for 1993-2009 were obtained from the Ministry of Health.
Meteorological data was obtained from NIWA. Generalised linear mixed models were
used to estimate the effects of three different components of variation in
temperature: geographical, seasonal and irregular. Irregular (random) daily
variation in temperature had a modest positive relationship with the incidence of
acts of self-harm resulting in hospitalisation, with about 0.7% extra incidents
for every 1 degrees C increase in temperature. However, there was no strong
evidence for a positive effect of either seasonal or geographical variation in
temperature. We conclude that temperature does appear to bear some relation to
the incidence of self-harm, with irregular daily variation in temperature having
a positive effect. However, inconsistencies in the effects of different
components of variation in temperature make it challenging to accurately predict
how global warming will influence the incidence of self-harm.
PMID- 25849086
TI - Use of nuclear magnetic resonance-based metabolomics to characterize the
biochemical effects of naphthalene on various organs of tolerant mice.
AB - Naphthalene, the most common polycyclic aromatic hydrocarbon, causes airway
epithelium injury in mice. Repeated exposure of mice to naphthalene induces
airway epithelia that are resistant to further injury. Previous studies revealed
that alterations in bioactivation enzymes and increased levels of gamma
glutamylcysteine synthase in the bronchioles protect tolerant mice from
naphthalene and its reactive metabolites. In our current study, tolerance was
induced in male ICR mice using a total of 7 daily intraperitoneal injections of
naphthalene (200 mg/kg). Both naphthalene-tolerant and non-tolerant mice were
challenged with a dose of 300 mg/kg naphthalene on day 8 to investigate
metabolite differences. The lungs, liver, and kidneys were collected for
histopathology 24 h after the challenge dose. Bronchial alveolar lavage fluid
(BALF) and both hydrophilic and hydrophobic extracts from each organ were
analyzed using nuclear magnetic resonance (NMR)-based metabolomics. The
histological results showed no observable injuries to the airway epithelium of
naphthalene-tolerant mice when compared with the control. In contrast, airway
injuries were observed in mice given a single challenge dose (injury mice). The
metabolomics analysis revealed that the energy metabolism in the lungs of
tolerant and injury mice was significantly perturbed. However, antioxidant
metabolites, such as glutathione and succinate, were significantly increased in
the lungs of tolerant mice, suggesting a role for these compounds in the
protection of organs from naphthalene-induced electrophilic metabolites and free
radicals. Damage to the airway cellular membrane, as shown by histopathological
results and increased acetone in the BALF and perturbation of hydrophobic lung
extracts, including cholesterol, phosphorylcholine-containing lipids, and fatty
acyl chains, were observed in injury mice. Consistent with our histopathological
results, fewer metabolic effects were observed in the liver and kidney of mice
after naphthalene treatments. In conclusion, NMR-based metabolomics reveals
possible mechanisms of naphthalene tolerance and naphthalene-induced toxicity in
the respiratory system of mice.
PMID- 25849088
TI - Bubble-induced cave collapse.
AB - Conventional wisdom among cave divers is that submerged caves in aquifers, such
as in Florida or the Yucatan, are unstable due to their ever-growing size from
limestone dissolution in water. Cave divers occasionally noted partial cave
collapses occurring while they were in the cave, attributing this to their
unintentional (and frowned upon) physical contact with the cave walls or the
aforementioned "natural" instability of the cave. Here, we suggest that these
cave collapses do not necessarily result from cave instability or contacts with
walls, but rather from divers bubbles rising to the ceiling and reducing the
buoyancy acting on isolated ceiling rocks. Using familiar theories for the
strength of flat and arched (un-cracked) beams, we first show that the flat
ceiling of a submerged limestone cave can have a horizontal expanse of 63 meters.
This is much broader than that of most submerged Florida caves (~ 10 m).
Similarly, we show that an arched cave roof can have a still larger expanse of
240 meters, again implying that Florida caves are structurally stable. Using
familiar bubble dynamics, fluid dynamics of bubble-induced flows, and accustomed
diving practices, we show that a group of 1-3 divers submerged below a loosely
connected ceiling rock will quickly trigger it to fall causing a "collapse". We
then present a set of qualitative laboratory experiments illustrating such a
collapse in a circular laboratory cave (i.e., a cave with a circular cross
section), with concave and convex ceilings. In these experiments, a metal ball
represented the rock (attached to the cave ceiling with a magnet), and the
bubbles were produced using a syringe located at the cave floor.
PMID- 25849090
TI - The correlation between running economy and maximal oxygen uptake: cross
sectional and longitudinal relationships in highly trained distance runners.
AB - A positive relationship between running economy and maximal oxygen uptake
(VO2max) has been postulated in trained athletes, but previous evidence is
equivocal and could have been confounded by statistical artefacts. Whether this
relationship is preserved in response to running training (changes in running
economy and VO2max) has yet to be explored. This study examined the relationships
of (i) running economy and VO2max between runners, and (ii) the changes in
running economy and VO2max that occur within runners in response to habitual
training. 168 trained distance runners (males, n = 98, VO2max 73.0 +/- 6.3 mL?kg
1?min-1; females, n = 70, VO2max 65.2 +/- 5.9 mL kg-1?min-1) performed a
discontinuous submaximal running test to determine running economy (kcal?km-1). A
continuous incremental treadmill running test to volitional exhaustion was used
to determine VO2max 54 participants (males, n = 27; females, n = 27) also
completed at least one follow up assessment. Partial correlation analysis
revealed small positive relationships between running economy and VO2max (males r
= 0.26, females r = 0.25; P<0.006), in addition to moderate positive
relationships between the changes in running economy and VO2max in response to
habitual training (r = 0.35; P<0.001). In conclusion, the current investigation
demonstrates that only a small to moderate relationship exists between running
economy and VO2max in highly trained distance runners. With >85% of the variance
in these parameters unexplained by this relationship, these findings reaffirm
that running economy and VO2max are primarily determined independently.
PMID- 25849091
TI - Effects of Temperature, Humidity and Air Flow on Fungal Growth Rate on Loaded
Ventilation Filters.
AB - This study compares the fungal growth ratio on loaded ventilation filters under
various temperature, relative humidity (RH), and air flow conditions in a
controlled laboratory setting. A new full-size commercial building ventilation
filter was loaded with malt extract nutrients and conidia of Cladosporium
sphaerospermum in an ASHRAE Standard 52.2 filter test facility. Small sections
cut from this filter were incubated under the following conditions: constant room
temperature and a high RH of 97%; sinusoidal temperature (with an amplitude of 10
degrees C, an average of 23 degrees C, and a period of 24 hr) and a mean RH of
97%; room temperature and step changes between 97% and 75% RH, 97% and 43% RH,
and 97% and 11% RH every 12 hr. The biomass on the filter sections was measured
using both an elution-culture method and by ergosterol assay immediately after
loading and every 2 days up to 10 days after loading. Fungal growth was detected
earlier using ergosterol content than with the elution-culture method. A
student's t-test indicated that Cladosporium sphaerospermum grew better at the
constant room temperature condition than at the sinusoidal temperature condition.
By part-time exposure to dry environments, the fungal growth was reduced (75% and
43% RH) or even inhibited (11% RH). Additional loaded filters were installed in
the wind tunnel at room temperature and an RH greater than 95% under one of two
air flow test conditions: continuous air flow or air flow only 9 hr/day with a
flow rate of 0.7 m(3)/s (filter media velocity 0.15 m/s). Swab tests and a tease
mount method were used to detect fungal growth on the filters at day 0, 5, and
10. Fungal growth was detected for both test conditions, which indicates that
when temperature and relative humidity are optimum, controlling the air flow
alone cannot prevent fungal growth. In real applications where nutrients are less
sufficient than in this laboratory study, fungal growth rate may be reduced under
the same operating conditions.
PMID- 25849089
TI - Association of small dense LDL serum levels and circulating monocyte subsets in
stable coronary artery disease.
AB - OBJECTIVE: Atherosclerosis is considered to be an inflammatory disease in which
monocytes and monocyte-derived macrophages play a key role. Circulating monocytes
can be divided into three distinct subtypes, namely in classical monocytes (CM;
CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical
monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous
in size and density, with small, dense LDL (sdLDL) crucially implicated in
atherogenesis. The aim of this study was to examine whether monocyte subsets are
associated with sdLDL serum levels. METHODS: We included 90 patients with
angiographically documented stable coronary artery disease and determined
monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis
method on polyacrylamide gel. RESULTS: Patients with sdLDL levels in the highest
tertile (sdLDL>=4mg/dL;T3) showed the highest levels of pro-inflammatory NCM
(15.2+/-7% vs. 11.4+/-6% and 10.9+/-4%, respectively; p<0.01) when compared with
patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0
1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM
levels than patients in the middle and lowest tertile (79.2+/-8% vs. 83.9+/-7%
and 82.7+/-5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL
levels (5.6+/-4% vs. 4.6+/-3% vs. 6.4+/-3% for T3, T2 and T1, respectively). In
contrast to monocyte subset distribution, levels of circulating pro- and anti
inflammatory markers were not associated with sdLDL levels. CONCLUSION: The
atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and
a decrease of CM. This could be a new link between lipid metabolism
dysregulation, innate immunity and atherosclerosis.
PMID- 25849092
TI - The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced
benign prostatic hyperplasia in rats.
AB - Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary
system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3
polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti
inflammatory and tumour-growth inhibitory effects. Here, the therapeutic
potential of DHA in treating BPH was investigated. Seal oil effectively prevented
the development of prostatic hyperplasia induced by oestradiol/testosterone in a
rat model by suppressing the increase of the prostatic index (PI), reducing the
thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation
of both prostate epithelial and stromal cells, and downregulating the expression
of androgen receptor (AR) and oestrogen receptor alpha (ERalpha). An in vitro
study showed that DHA inhibited the growth of the human prostate stromal cell
line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent
manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In
addition, DHA also reduced the expression of ERalpha and AR in the WPMY-1 and
RWPE-1 cells. These results indicate that DHA inhibits the multiplication of
prostate stromal and epithelial cells through a mechanism that may involve cell
cycle arrest and the downregulation of ERalpha and AR expression.
PMID- 25849093
TI - AceCloud: Molecular Dynamics Simulations in the Cloud.
AB - We present AceCloud, an on-demand service for molecular dynamics simulations.
AceCloud is designed to facilitate the secure execution of large ensembles of
simulations on an external cloud computing service (currently Amazon Web
Services). The AceCloud client, integrated into the ACEMD molecular dynamics
package, provides an easy-to-use interface that abstracts all aspects of
interaction with the cloud services. This gives the user the experience that all
simulations are running on their local machine, minimizing the learning curve
typically associated with the transition to using high performance computing
services.
PMID- 25849094
TI - The effect of using an audience response system on learning, motivation and
information retention in the orthodontic teaching of undergraduate dental
students: a cross-over trial.
AB - OBJECTIVE: New methods of teaching and learning are constantly being sought in
the adult learning environment. Audience Response Systems (ARS) have been used in
many different learning environments, especially in the field of medical
education. The objective of this investigation was to ascertain the effect of ARS
use in undergraduate teaching in a UK dental school. DESIGN: A cross-over
clustered randomized educational trial. SETTING: Leeds Dental Institute.
PARTICIPANTS: Year 4 undergraduate dental students in orthodontics. METHODS:
Students at Leeds Dental Institute were taught two different topics within the
curriculum to test the use of ARS in a cross-over trial. A questionnaire was
delivered to the test (ARS) and control (non-ARS) groups. RESULTS: The response
rate to the questionnaires was 89.5% (test group) and 82.9% (control group). The
ARS enabled students to perform better as shown by knowledge retention (P =
0.013). Students found the seminar more interesting (P = 0.013), easier to
concentrate (P = 0.025) and easier to participate in (P = 0.020) when ARS was
used. When ARS was used, students were more able to answer questions (P<0.0001),
were more likely to prepare for the seminar (P<0.0001) and significantly
preferred using ARS (P<0.0001). CONCLUSIONS: ARS was found to significantly
improve student concentration and participation in small group seminar teaching
and significantly improved knowledge retention. ARS may be useful in facilitating
orthodontic teaching in the future.
PMID- 25849096
TI - An evaluation of nearly-extinct cohort methods for estimating the very elderly
populations of australia and new zealand.
AB - The rapid growth of very elderly populations requires accurate population
estimates up to the highest ages. However, it is recognised that estimates
derived from census counts are often unreliable. Methods that make use of death
data have not previously been evaluated for Australia and New Zealand. The aim
was to evaluate a number of nearly-extinct cohort methods for producing very
elderly population estimates by age and sex for Australia and New Zealand. The
accuracy of official estimates was also assessed. Variants of three nearly
extinct cohort methods, the Survivor Ratio method, the Das Gupta method and a new
method explicitly allowing for falling mortality over time, were evaluated by
retrospective application over the period 1976-1996. Estimates by sex and single
years of age were compared against numbers derived from the extinct cohort
method. Errors were measured by the Weighted Mean Absolute Percentage Error. It
is confirmed that for Australian females the Survivor Ratio method constrained to
official estimates for ages 90+ performed well. However, for Australian males and
both sexes in New Zealand, more accurate estimates were obtained by constraining
the Survivor Ratio method to official estimates for ages 85+. Official estimates
in Australia proved reasonably accurate for ages 90+ but at 100+ they varied
significantly in accuracy from year to year. Estimates produced by Statistics New
Zealand in aggregate for ages 90+ proved very accurate. We recommend the use of
the Survivor Ratio method constrained to official estimates for ages 85+ to
create very elderly population estimates for Australia and New Zealand.
PMID- 25849095
TI - Interneuron epigenomes during the critical period of cortical plasticity:
Implications for schizophrenia.
AB - Schizophrenia, a major psychiatric disorder defined by delusions and
hallucinations, among other symptoms, often with onset in early adulthood, is
potentially associated with molecular and cellular alterations in parvalbumin
expressing fast spiking interneurons and other constituents of the cortical
inhibitory GABAergic circuitry. The underlying mechanisms, including the role of
disease-associated risk factors operating in adolescence such as drug abuse and
social stressors, remain incompletely understood. Here, we summarize emerging
findings from animal models, highlighting the ability of parvalbuminergic
interneurons (PVI) to induce, during the juvenile period, long-term plastic
changes in prefrontal and visual cortex, thereby altering perception, cognition
and behavior in the adult. Of note, molecular alterations in PVI from subjects
with schizophrenia, including downregulated expression of a subset of GABAergic
genes, have also been found in juvenile stress models of the disorder. Some of
the transcriptional alterations observed in schizophrenia postmortem brain could
be linked to changes in the epigenetic architecture of GABAergic gene promoters,
including dysregulated DNA methylation, histone modification patterns and
disruption of promoter-enhancer interactions at site of chromosomal loop
formations. Therefore, we predict that, in the not-to-distant future, PVI- and
other cell-type specific epigenomic mappings in the animal model and human brain
will provide novel insights into the pathophysiology of schizophrenia and related
psychotic diseases, including the role of cortical GABAergic circuitry in shaping
long-term plasticity and cognitive function of the cerebral cortex.
PMID- 25849097
TI - Plasmodium falciparum susceptibility to standard and potential anti-malarial
drugs in Dakar, Senegal, during the 2013-2014 malaria season.
AB - BACKGROUND: In 2006, the Senegalese National Malaria Control Programme
recommended artemisinin-based combination therapy (ACT) as the first-line
treatment for uncomplicated malaria. Since the introduction of ACT, there have
been very few reports on the level of Plasmodium falciparum resistance to anti
malarial drugs. An ex vivo susceptibility study was conducted on local isolates
obtained from the Hopital Principal de Dakar (Dakar, Senegal) from November 2013
to January 2014. METHODS: Eighteen P. falciparum isolates were sussessfully
assessed for ex vivo susceptibility to chloroquine (CQ), quinine (QN),
monodesethylamodiaquine (MDAQ), the active metabolite of amodiaquine, mefloquine
(MQ), lumefantrine (LMF), artesunate (AS), dihydroartemisinin (DHA), the active
metabolite of artemisinin derivatives, pyronaridine (PND), piperaquine (PPQ),
and, Proveblue (PVB), a methylene blue preparation, using the HRP2-based ELISA
test. RESULTS: The prevalence of isolates with reduced susceptibility was 55.6%
for MQ, 50% for CQ, 5.6% for QN and MDAQ, and 0% for DHA, AS and LMF. The mean
IC50 for PND, PPQ and PVB were 5.8 nM, 32.2 nM and 5.3 nM, respectively.
CONCLUSIONS: The prevalence of isolates with a reduced susceptibility to MQ
remains high and stable in Dakar. Since 2004, the prevalence of CQ resistance
decreased, but rebounded in 2013 in Dakar. PND, PPQ and PVB showed high in vitro
activity in P. falciparum parasites from Dakar.
PMID- 25849098
TI - Electro-response characteristic of starch hydrogel crosslinked with
Glutaraldehyde.
AB - The facile synthesis of the starch hydrogel with anisotropic microstructure and
dynamic behaviors was developed in the presence (A-gel) and absence of DC
electric field (B-gel). The microstructures of hydrogels were characterized by
environmental scanning electron microscope. Their electro-responsive property of
hydrogels was investigated with their storage modulus (G'). The result
demonstrates that the G' of A-gel is greater than that of B-gel, and the modulus
of A-gel increases along with the external field, which signifies positive
electroresponse. In addition, the G' of A-gel and B-gel ((G'(A) and G'(B)) also
continuously increases with increasing starch concentration, whereas both the
maximum of modulus increment (DeltaG' = G'(A)-G'(B) ) and that of modulus
increment sensitivity (DeltaG'/G'(B)) occur with the starch weight fraction at
around 36.5%. To enhance the electro-responsive effects of the hydrogels,
dielectric particles were dispersed in the hydrogel. It is found that
BaTiO3/chitosan core-shell composite particles significantly enhance the
electroresponse of the hydrogel. The mechanism of the electro-response mode is
proposed.
PMID- 25849099
TI - Li adsorption, hydrogen storage and dissociation using monolayer MoS2: an ab
initio random structure searching approach.
AB - Utilizing ab initio random structure searching, we investigated Li adsorption on
MoS2 and hydrogen molecules on Li-decorated MoS2. In contrast to graphene, Li can
be adsorbed on both sides of MoS2, with even stronger binding than on the single
side. We found that high coverages of Li can be attained without Li clustering,
which is essential for hydrogen storage and Li ion batteries. Moreover, regarding
battery applications, Li diffusion was also found to be easy. The fully-lithiated
MoS2 can then adsorb H2 with 4.4 wt%. Interestingly, our calculations revealed
that hydrogen molecules can be dissociated at high Li coverage with a minimal
energy barrier. We further showed that the dissociated hydrogen atom can readily
diffuse on the surface, thus keeping the reaction site active. We therefore
propose that Li-MoS2 could be an inexpensive alternative catalyst to noble metals
in hydrogen dissociation reactions.
PMID- 25849100
TI - A multistep high-content screening approach to identify novel functionally
relevant target genes in pancreatic cancer.
AB - In order to foster the systematic identification of novel genes with important
functional roles in pancreatic cancer, we have devised a multi-stage screening
strategy to provide a rational basis for the selection of highly relevant novel
candidate genes based on the results of functional high-content analyses. The
workflow comprised three consecutive stages: 1) serial gene expression profiling
analyses of primary human pancreatic tissues as well as a number of in vivo and
in vitro models of tumor-relevant characteristics in order to identify genes with
conspicuous expression patterns; 2) use of 'reverse transfection array'
technology for large-scale parallelized functional analyses of potential
candidate genes in cell-based assays; and 3) selection of individual candidate
genes for further in-depth examination of their cellular roles. A total of 14
genes, among them 8 from "druggable" gene families, were classified as high
priority candidates for individual functional characterization. As an example to
demonstrate the validity of the approach, comprehensive functional data on
candidate gene ADRBK1/GRK2, which has previously not been implicated in
pancreatic cancer, is presented.
PMID- 25849101
TI - Breast cancer biology and ethnic disparities in breast cancer mortality in new
zealand: a cohort study.
AB - INTRODUCTION: Indigenous Maori women have a 60% higher breast cancer mortality
rate compared with European women in New Zealand. We investigated differences in
cancer biological characteristics and their impact on breast cancer mortality
disparity between Maori and NZ European women. MATERIALS AND METHODS: Data on
2849 women with primary invasive breast cancers diagnosed between 1999 and 2012
were extracted from the Waikato Breast Cancer Register. Differences in
distribution of cancer biological characteristics between Maori and NZ European
women were explored adjusting for age and socioeconomic deprivation in logistic
regression models. Impacts of socioeconomic deprivation, stage and cancer
biological characteristics on breast cancer mortality disparity between Maori and
NZ European women were explored in Cox regression models. RESULTS: Compared with
NZ European women (n=2304), Maori women (n=429) had significantly higher rates of
advanced and higher grade cancers. Maori women also had non-significantly higher
rates of ER/PR negative and HER-2 positive breast cancers. Higher odds of
advanced stage and higher grade remained significant for Maori after adjusting
for age and deprivation. Maori women had almost a 100% higher age and deprivation
adjusted breast cancer mortality hazard compared with NZ European women (HR=1.98,
1.55-2.54). Advanced stage and lower proportion of screen detected cancer in
Maori explained a greater portion of the excess breast cancer mortality (HR
reduction from 1.98 to 1.38), while the additional contribution through
biological differences were minimal (HR reduction from 1.38 to 1.35).
CONCLUSIONS: More advanced cancer stage at diagnosis has the greatest impact
while differences in biological characteristics appear to be a minor contributor
for inequities in breast cancer mortality between Maori and NZ European women.
Strategies aimed at reducing breast cancer mortality in Maori should focus on
earlier diagnosis, which will likely have a greater impact on reducing breast
cancer mortality inequity between Maori and NZ European women.
PMID- 25849102
TI - Intra-abdominal pressure correlates with extracellular water content.
AB - BACKGROUND: Secondary increase in intra-abdominal pressure (IAP) may result from
extra-abdominal pathology, such as massive fluid resuscitation, capillary leak or
sepsis. All these conditions increase the extravascular water content. The aim of
this study was to analyze the relationship between IAP and body water volume.
MATERIAL AND METHODS: Adult patients treated for sepsis or septic shock with
acute kidney injury (AKI) and patients undergoing elective pharyngolaryngeal or
orthopedic surgery were enrolled. IAP was measured in the urinary bladder. Total
body water (TBW), extracellular water content (ECW) and volume excess (VE) were
measured by whole body bioimpedance. Among critically ill patients, all
parameters were analyzed over three consecutive days, and parameters were
evaluated perioperatively in surgical patients. RESULTS: One hundred twenty
patients were studied. Taken together, the correlations between IAP and VE, TBW,
and ECW were measured at 408 time points. In all participants, IAP strongly
correlated with ECW and VE. In critically ill patients, IAP correlated with ECW
and VE. In surgical patients, IAP correlated with ECW and TBW. IAP strongly
correlated with ECW and VE in the mixed population. IAP also correlated with VE
in critically ill patients. ROC curve analysis showed that ECW and VE might be
discriminative parameters of risk for increased IAP. CONCLUSION: IAP strongly
correlates with ECW.
PMID- 25849104
TI - Chiral gold phosphate catalyzed tandem hydroamination/asymmetric transfer
hydrogenation enables access to chiral tetrahydroquinolines.
AB - A highly efficient chiral gold phosphate-catalyzed tandem
hydroamination/asymmetric transfer hydrogenation reaction is described. A series
of chiral tetrahydroquinolines were obtained in excellent yields and
enantioselectivities. In this reaction, the gold catalyst enables both the
hydroamination step as a pi-Lewis acid and the asymmetric hydrogen-transfer
process as an effective chiral Lewis acid.
PMID- 25849103
TI - Parallel action of AtDRB2 and RdDM in the control of transposable element
expression.
AB - BACKGROUND: In plants and animals, a large number of double-stranded RNA binding
proteins (DRBs) have been shown to act as non-catalytic cofactors of DICERs and
to participate in the biogenesis of small RNAs involved in RNA silencing. We have
previously shown that the loss of Arabidopsis thaliana's DRB2 protein results in
a significant increase in the population of RNA polymerase IV (p4) dependent
siRNAs, which are involved in the RNA-directed DNA methylation (RdDM) process.
RESULTS: Surprisingly, despite this observation, we show in this work that DRB2
is part of a high molecular weight complex that does not involve RdDM actors but
several chromatin regulator proteins, such as MSI4, PRMT4B and HDA19. We show
that DRB2 can bind transposable element (TE) transcripts in vivo but that drb2
mutants do not have a significant variation in TE DNA methylation. CONCLUSION: We
propose that DRB2 is part of a repressive epigenetic regulator complex involved
in a negative feedback loop, adjusting epigenetic state to transcription level at
TE loci, in parallel of the RdDM pathway. Loss of DRB2 would mainly result in an
increased production of TE transcripts, readily converted in p4-siRNAs by the
RdDM machinery.
PMID- 25849105
TI - Single-particle absorption spectroscopy by photothermal contrast.
AB - Removing effects of sample heterogeneity through single-molecule and single
particle techniques has advanced many fields. While background free luminescence
and scattering spectroscopy is widely used, recording the absorption spectrum
only is rather difficult. Here we present an approach capable of recording pure
absorption spectra of individual nanostructures. We demonstrate the
implementation of single-particle absorption spectroscopy on strongly scattering
plasmonic nanoparticles by combining photothermal microscopy with a
supercontinuum laser and an innovative calibration procedure that accounts for
chromatic aberrations and wavelength-dependent excitation powers. Comparison of
the absorption spectra to the scattering spectra of the same individual gold
nanoparticles reveals the blueshift of the absorption spectra, as predicted by
Mie theory but previously not detectable in extinction measurements that measure
the sum of absorption and scattering. By covering a wavelength range of 300 nm,
we are furthermore able to record absorption spectra of single gold nanorods with
different aspect ratios. We find that the spectral shift between absorption and
scattering for the longitudinal plasmon resonance decreases as a function of
nanorod aspect ratio, which is in agreement with simulations.
PMID- 25849107
TI - Amperometric detection of extended-spectrum beta-lactamase activity: application
to the characterization of resistant E. coli strains.
AB - The amperometric detection of extended-spectrum beta-lactamase (ESBL) with carbon
screen-printed sensors was investigated in the presence of the Nitrocefin, a
commercially-available beta-lactamase chromogenic cephalosporin substrate. Using
an ESBL isolated from a clinical sample, it was shown for the first time that the
intensity of a specific anodic pic current (EP = ~+0.3 V vs. Ag/AgCl) resulting
from the catalytic hydrolysis of the beta-lactam ring was proportional to the
amount of ESBL. The proof-of-principle of a novel susceptibility assay for the
rapid and accurate identification of ESBL- producing bacteria was then
demonstrated. The detection scheme relied on (i) the culture of the sample in a
medium containing the cefotaxime supplemented or not with the clavulanic acid
inhibitor to allow the specific determination of ESBL producers (ii) followed by
the incubation of the bacteria with the Nitrocefin and (iii) the measurement of
the enzyme product by cyclic voltammetry. The amperometric assay was further
applied to the characterization of E. coli strains and to the quantification of
the ESBL producers. A detection limit of 5 * 10(4) cfu mL(-1) ESBL-producing E.
coli was achieved after a 10 min incubation time. In contrast to the approved
routine assays, the electrochemical approach, which did not require isolated
colonies to be performed, provided quantified results regarding ESBL activity
within a few hours. Finally, owing to its cost-effectiveness, portability and
simplicity, this test holds great promise for clinical and environmental
applications.
PMID- 25849106
TI - Invasive lobular carcinoma of the breast: morphology, biomarkers and 'omics.
AB - Invasive lobular carcinoma of the breast is the most common 'special'
morphological subtype of breast cancer, comprising up to 15% of all cases.
Tumours are generally of a good prognostic phenotype, being low histological
grade and low mitotic index, hormone receptor positive and HER2, p53 and basal
marker negative, and with a generally good response to endocrine therapy. Despite
this, clinicians face countless challenges in the diagnosis and long-term
management of patients, as they encounter a tumour that can be difficult to
detect through screening, elicits a very invasive nature, a propensity for
widespread metastatic colonisation and, consequently, in some studies a worse
long-term poor outcome compared with invasive carcinoma of no special type. Here
we review the morphological and molecular features that underpin the disparate
biological and clinical characteristics of this fascinating tumour type.
PMID- 25849108
TI - Orthodontic treatment of a particular subgroup of children with special health
care needs, children with craniofacial anomalies: An analysis of treatment length
and clinical outcome.
AB - OBJECTIVE: To analyze any differences in the orthodontic treatment between
children belonging to a particular subgroup of subjects with special health care
needs (SHCN), children with craniofacial anomalies (CFA), and children not
diagnosed with SHCN (NO SHCN). MATERIALS AND METHODS: The study sample consisted
of 50 children with SHCN and a confirmed diagnosis of CFA (SHCN/CFA); the control
group consisted of 50 NO SHCN children fully matched for age, gender, and type of
appliance used. The differences between the two groups were analyzed
retrospectively: pre-, posttreatment scores, and score reduction of the Peer
Assessment Rating Index (PAR), dental health component (DHC), and aesthetic
component (AC) of Orthodontic Treatment Need Index (IOTN), number of
appointments, number of simple or complex chair-time appointments, overall
treatment time, and age at treatment start and end. RESULTS: There were no
statistically significant differences between the SHCN/CFA and NO SHCN groups for
number of appointments, overall treatment time, age at treatment start, and age
at treatment end (P = .682, .458, .535, and .675, respectively). There were
statistically significant differences between groups in PAR, DHC, AC pre- and
posttreatment, and number of simple and complex chair-time appointments (P =
.030 and .000; .020 and .023; .000 and .000; .043; and .037; respectively). The
reduction of PAR, DHC, and AC scores was not significantly different between
groups (P = .060, .765, and .825, respectively). CONCLUSION: The treatment of
children with SHCN, in general, and with CFA, in particular, on the one hand
involves a higher rate of using complex chair time appointments and an inferior
treatment outcome, by the other side implies an overall treatment time and a
reduction of PAR, DHC or AC scores similar to the treatment of children not
diagnosed with SHCN.
PMID- 25849109
TI - Changes in the endurance shuttle walk test in COPD patients with chronic
respiratory failure after pulmonary rehabilitation: the minimal important
difference obtained with anchor- and distribution-based method.
AB - BACKGROUND: Although the endurance shuttle walk test (ESWT) has proven to be
responsive to change in exercise capacity after pulmonary rehabilitation (PR) for
COPD, the minimally important difference (MID) has not yet been established. We
aimed to establish the MID of the ESWT in patients with severe COPD and chronic
hypercapnic respiratory failure following PR. METHODS: Data were derived from a
randomized controlled trial, investigating the value of noninvasive positive
pressure ventilation added to PR. Fifty-five patients with stable COPD, GOLD
stage IV, with chronic respiratory failure were included (mean (SD) FEV1 31.1
(12.0) % pred, age 62 (9) y). MID estimates of the ESWT in seconds, percentage
and meters change were calculated with anchor based and distribution based
methods. Six minute walking distance (6MWD), peak work rate on bicycle ergometry
(Wpeak) and Chronic Respiratory Questionnaire (CRQ) were used as anchors and
Cohen's effect size was used as distribution based method. RESULTS: The estimated
MID of the ESWT with the different anchors ranged from 186-199 s, 76-82% and 154
164 m. Using the distribution based method the MID was 144 s, 61% and 137 m.
CONCLUSIONS: Estimates of the MID for the ESWT after PR showed only small
differences using different anchors in patients with COPD and chronic respiratory
failure. Therefore we recommend using a range of 186-199 s, 76-82% or 154-164 m
as MID of the ESWT in COPD patients with chronic respiratory failure. Further
research in larger populations should elucidate whether this cut-off value is
also valid in other COPD populations and with other interventions. TRIAL
REGISTRATION: ClinicalTrials.Gov (ID NCT00135538).
PMID- 25849110
TI - Recombinant hamster oviductin is biologically active and exerts positive effects
on sperm functions and sperm-oocyte binding.
AB - Studies carried out in several mammalian species suggest that oviductin, also
known as oviduct-specific glycoprotein or OVGP1, plays a key role in sperm
capacitation, fertilization, and development of early embryos. In the present
study, we used recombinant DNA technology to produce, for the first time,
recombinant hamster OVGP1 (rHamOVGP1) in human embryonic kidney 293 (HEK293)
cells. rHamOVGP1 secreted in the culture medium was purified by affinity
chromatography. The resulting protein migrated as a poly-dispersed band of 160
350 kDa on SDS-PAGE corresponding to the molecular mass of the native HamOVGP1.
Subsequent mass spectrometric analysis of the purified rHamOVGP1 confirmed its
identity as HamOVGP1. Immunocytochemistry demonstrated binding of rHamOVGP1 to
the mid-piece and head of hamster sperm and to the zona pellucida (ZP) of ovarian
oocytes. In vitro functional experiments showed that addition of rHamOVGP1 in the
capacitation medium further enhanced tyrosine phosphorylation of two sperm
proteins of approximately 75 kDa and 83 kDa in a time-dependent manner. After 3
hours of incubation in the presence of rHamOVGP1, a significant increase in
acrosome reaction was measured. Pretreatment of either sperm or oocyte with 20
MUg/ml of rHamOVGP1 prior to sperm-egg binding assay significantly increased the
number of sperm bound to the ZP. Addition of rHamOVGP1 in the medium during sperm
egg binding with either oocyte or sperm pretreated with rHamOVGP1 also saw an
increase in the number of sperm bound to ZP. In all experimental conditions, the
effect of rHamOVGP1 on sperm-oocyte binding was negated by the addition of
monoclonal anti-HamOVGP1 antibody. The successful production and purification of
a biologically active rHamOVGP1 will allow further exploration of the function of
this glycoprotein in reproductive function.
PMID- 25849111
TI - Estimated dietary dioxin exposure and breast cancer risk among women from the
French E3N prospective cohort.
AB - INTRODUCTION: Dioxins are environmental and persistent pollutants mostly emitted
from combustion facilities (e.g. waste incinerators, metal and cement
industries). Known to be endocrine disrupting chemicals, dioxins are suspected to
increase breast cancer (BC) risk. Although diet is considered the primary source
of dioxin exposure, no previous study has been published on dietary dioxin
exposure in relation to BC risk. We aimed to assess dietary dioxin exposure among
women from the E3N cohort and estimate BC risk associated with this exposure.
METHODS: The study included 63,830 women from the E3N cohort who completed a diet
history questionnaire (DHQ) in 1993 and were followed until 2008. Dietary dioxin
exposure was estimated by combining consumption data from the E3N DHQ and food
dioxin contamination data from a French national monitoring program. Hazard
ratios (HR) and 95% confidence intervals (CI) were estimated by Cox models
adjusted for BC risk factors. RESULTS: Mean dietary dioxin exposure was estimated
at 1.3 +/- 0.4 pg/kg body weight (BW)/day. A 0.4 pg/kg BW/d increase in dioxin
intake was not associated with overall BC risk (HR = 1.00; 95% CI: 0.96, 1.05). A
significant decrease in risk of estrogen receptor negative (ER-)/progesterone
receptor negative (PR-) tumors was observed among post-menopausal women in the
upper quartile of estimated dioxin intake (HR for Q4 vs. Q1: 0.65; 95% CI: 0.45,
0.96; P for trend across quartiles = 0.0463). CONCLUSIONS: Overall, no
association between estimated dietary dioxin exposure and BC risk was found among
E3N women. Further studies should include both dietary and environmental
exposures to determine whether low-dose dioxin exposure is associated with BC
risk.
PMID- 25849112
TI - Analysis of new isolates reveals new genome organization and a hypervariable
region in infectious myonecrosis virus (IMNV).
AB - Infectious myonecrosis virus (IMNV) has been the cause of many losses in shrimp
farming since 2002, when the first myonecrosis outbreak was reported at
Brazilian's northeast coast. Two additional genomes of Brazilian IMNV isolates
collected in 2009 and 2013 were sequenced and analyzed in the present study. The
sequencing revealed extra 643 bp and 22 bp, at 5' and 3' ends of IMNV genome
respectively, confirming that its actual size is at least 8226 bp long.
Considering these additional sequences in genome extremities, ORF1 can starts at
nt 470, encoding a 1708 aa polyprotein. Computational predictions reveal two stem
loops and two pseudoknots in the 5' end and a putative stem loop and a slippery
motif located at 3' end, indicating that these regions can be involved in the
start and termination of translation. Through a careful phylogenetic analysis, a
higher genetic variability among Brazilian isolates could be observed, comparing
with Indonesian IMNV isolates. It was also observed that the most variable region
of IMNV genome is located in the first half of ORF1, coinciding with a region
which probably encodes the capsid protrusions. The results presented here are a
starting point to elucidate the viral's translational regulation and the
mechanisms involved in virulence.
PMID- 25849114
TI - A predictive approach to CVD of crystalline layers of TMDs: the case of MoS2.
AB - Layered transition metal dichalcogenides (TMDs), such as MoS2, are candidate
materials for next generation 2-D electronic and optoelectronic devices. The
ability to grow uniform, crystalline, atomic layers over large areas is the key
to developing such technology. We report a chemical vapor deposition (CVD)
technique which yields n-layered MoS2 on a variety of substrates. A generic
approach suitable to all TMDs, involving thermodynamic modeling to identify the
appropriate CVD process window, and quantitative control of the vapor phase
supersaturation, is demonstrated. All reactant sources in our method are outside
the growth chamber, a significant improvement over vapor-based methods for atomic
layers reported to date. The as-deposited layers are p-type, due to Mo
deficiency, with field effect and Hall hole mobilities of up to 2.4 cm(2) V(-1)
s(-1) and 44 cm(2) V(-1) s(-1) respectively. These are among the best reported
yet for CVD MoS2.
PMID- 25849113
TI - An economic evaluation of conception strategies for heterosexual serodiscordant
couples where the male partner is HIV-positive.
AB - BACKGROUND: To conduct an economic evaluation of the three commonly used
interventions that reduce sexual HIV transmission when an HIV-negative female
aims to conceive with an HIV-positive male on combination antiretroviral therapy
(condomless sex restricted to timed ovulation [CS], sperm washing with
intrauterine insemination [SW] and condomless sex restricted to timed ovulation
with pre-exposure prophylaxis [CS-PrEP]). As SW and CS-PrEP are only privately
available for pregnancy planning for this population in Canada, this study was
conducted to inform policy decisions concerning potential public health insurance
coverage, as well as to inform fertility counselling in settings with adequate
combination antiretroviral therapy access globally. METHODS: We developed a
cohort Markov model with a lifetime horizon and used the perspective of Ontario's
Ministry of Health (MOH). Input parameters were drawn from literature, the MOH's
Schedule of Benefits and a time trade-off questionnaire designed for this study.
Outcome measures included quality-adjusted life-years and incremental cost
effectiveness. Costs and benefits were discounted at annual rates of 3%. Costs
were reported in Canadian 2013 dollars and an exchange rate of 1 USD to 1.066 CND
was applied where necessary. Sensitivity analysis assessed the uncertainty of
model parameters. RESULTS: The base case analysis found that CS-PrEP and SW were
each more costly and less effective at conception than CS. The results were
robust in the sensitivity analysis and suggest that CS is the dominant conception
strategy in this population. CONCLUSIONS: Neither CS-PrEP nor SW represent better
value for money relative to CS as a conception option for HIV-discordant couples
with positive male partners. Based on these findings, CS-PrEP and SW cannot be
recommended for public-funding in developed countries.
PMID- 25849115
TI - Effectiveness of Rice Agricultural Waste, Microbes and Wetland Plants in the
Removal of Reactive Black-5 Azo Dye in Microcosm Constructed Wetlands.
AB - Azo dyes are commonly generated as effluent pollutants by dye using industries,
causing contamination of surface and ground water. Various strategies are
employed to treat such wastewater; however, a multi-faceted treatment strategy
could be more effective for complete removal of azo dyes from industrial effluent
than any single treatment. In the present study, rice husk material was used as a
substratum in two constructed wetlands (CWs) and augmented with microorganisms in
the presence of wetland plants to effectively treat dye-polluted water. To
evaluate the efficiency of each process the study was divided into three levels,
i.e., adsorption of dye onto the substratum, phytoremediation within the CW and
then bioremediation along with the previous two processes in the augmented CW.
The adsorption process was helpful in removing 50% dye in presence of rice husk
while 80% in presence of rice husk biocahr. Augmentation of microorganisms in CW
systems has improved dye removal efficiency to 90%. Similarly presence of
microorganisms enhanced removal of total nitrogen (68% 0 and Total phosphorus
(75%). A significant improvement in plant growth was also observed by measuring
plant height, number of leaves and leave area. These findings suggest the use of
agricultural waste as part of a CW substratum can provide enhanced removal of
textile dyes.
PMID- 25849116
TI - Optical protein detection based on magnetic clusters rotation.
AB - In this paper we present a simple method to quantify aggregates of 200nm magnetic
particles. This method relies on the optical and magnetic anisotropy of particle
aggregates, whereas dispersed particles are optically isotropic. We orientate
aggregates by applying short pulses of a magnetic field, and we measure optical
density variation directly linked to this reorientation. By computing the
scattering efficiency of doublets and singlets, we demonstrate the absolute
quantification of a few % of doublets in a well dispersed suspension. More
generally, these optical variations are related to the aggregation state of the
sample. This method can be easily applied to an agglutination assay, where target
proteins induce aggregation of colloidal particles. By observing only aligned
clusters, we increase sensitivity and we reduce the background noise as compared
to a classical agglutination assay: we obtain a detection limit on the C-reactive
protein of less than 3pM for a total assay time of 10min.
PMID- 25849117
TI - Stepwise catalytic mechanism via short-lived intermediate inferred from combined
QM/MM MERP and PES calculations on retaining glycosyltransferase ppGalNAcT2.
AB - The glycosylation of cell surface proteins plays a crucial role in a multitude of
biological processes, such as cell adhesion and recognition. To understand the
process of protein glycosylation, the reaction mechanisms of the participating
enzymes need to be known. However, the reaction mechanism of retaining
glycosyltransferases has not yet been sufficiently explained. Here we
investigated the catalytic mechanism of human isoform 2 of the retaining
glycosyltransferase polypeptide UDP-GalNAc transferase by coupling two different
QM/MM-based approaches, namely a potential energy surface scan in two distance
difference dimensions and a minimum energy reaction path optimisation using the
Nudged Elastic Band method. Potential energy scan studies often suffer from
inadequate sampling of reactive processes due to a predefined scan coordinate
system. At the same time, path optimisation methods enable the sampling of a
virtually unlimited number of dimensions, but their results cannot be
unambiguously interpreted without knowledge of the potential energy surface. By
combining these methods, we have been able to eliminate the most significant
sources of potential errors inherent to each of these approaches. The structural
model is based on the crystal structure of human isoform 2. In the QM/MM method,
the QM region consists of 275 atoms, the remaining 5776 atoms were in the MM
region. We found that ppGalNAcT2 catalyzes a same-face nucleophilic substitution
with internal return (SNi). The optimized transition state for the reaction is
13.8 kcal/mol higher in energy than the reactant while the energy of the product
complex is 6.7 kcal/mol lower. During the process of nucleophilic attack, a
proton is synchronously transferred to the leaving phosphate. The presence of a
short-lived metastable oxocarbenium intermediate is likely, as indicated by the
reaction energy profiles obtained using high-level density functionals.
PMID- 25849118
TI - Invariant natural killer T cells treated with rapamycin or transforming growth
factor-beta acquire a regulatory function and suppress T effector lymphocytes.
PMID- 25849119
TI - An imbalance between innate and adaptive immune cells at the maternal-fetal
interface occurs prior to endotoxin-induced preterm birth.
AB - Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality
worldwide. A transition from an anti-inflammatory state to a pro-inflammatory
state in the mother and at the maternal-fetal interface has been implicated in
the pathophysiology of microbial-induced preterm labor. However, it is unclear
which immune cells mediate this transition. We hypothesized that an imbalance
between innate and adaptive immune cells at the maternal-fetal interface will
occur prior to microbial-induced preterm labor. Using an established murine model
of endotoxin-induced PTB, our results demonstrate that prior to delivery there is
a reduction of CD4+ regulatory T cells (Tregs) in the uterine tissues. This
reduction is neither linked to a diminished number of Tregs in the spleen, nor to
an impaired production of IL10, CCL17, or CCL22 by the uterine tissues. Endotoxin
administration to pregnant mice does not alter effector CD4+ T cells at the
maternal-fetal interface. However, it causes an imbalance between Tregs (CD4+ and
CD8+), effector CD8+ T cells, and Th17 cells in the spleen. In addition,
endotoxin administration to pregnant mice leads to an excessive production of
CCL2, CCL3, CCL17, and CCL22 by the uterine tissues as well as abundant
neutrophils. This imbalance in the uterine microenvironment is accompanied by
scarce APC-like cells such as macrophages and MHC II+ neutrophils. Collectively,
these results demonstrate that endotoxin administration to pregnant mice causes
an imbalance between innate and adaptive immune cells at the maternal-fetal
interface.
PMID- 25849120
TI - Reversal of B-cell hyperactivation and functional impairment is associated with
HBsAg seroconversion in chronic hepatitis B patients.
AB - B cells play an important role in the clearance of hepatitis B virus (HBV) and
protection against reinfection. However, the functional characteristics of these
cells that are associated with the outcome of chronic HBV infection remain
unknown. We comprehensively investigated the frequency, phenotype, and function
of peripheral B-cell subsets from CHB patients in different phases: immune
tolerance (IT), immune activation (IA), immune clearance (IC), responders with
HBsAg seroconversion (resolved patients, RP), and healthy controls (HC). IA
patients displayed lower percentages of peripheral blood memory B cells compared
with the other groups. Overall polyclonal activation of B cells, indicated by
higher levels of activation markers and secretion of IgG and IgM, was observed in
IA patients. This B-cell hyperactivation could be induced by increased IFN-alpha
and soluble CD40 ligands in IA patients. Notably, the expression of the co
stimulator molecule CD80 and serum HBsAb and the frequency of HBsAg-specific B
cells were significantly decreased in IT, IA, and IC patients compared with HC
subjects. More importantly, the B-cell hyperactivation, co-stimulatory molecule
downregulation and HBsAg-specific B-cell impairment were reversed in RP patients.
The reversal of B-cell hyperactivation and functional impairment is associated
with HBsAg seroconversion in chronic hepatitis B patients.
PMID- 25849122
TI - Correction: a genomic screen revealing the importance of vesicular trafficking
pathways in genome maintenance and protection against genotoxic stress in diploid
Saccharomyces cerevisiae cells.
PMID- 25849121
TI - AID expression increased by TNF-alpha is associated with class switch
recombination of Igalpha gene in cancers.
AB - Recently, immunoglobulins (Igs) were unexpectedly found to be expressed in
epithelial cancers. Immunoglobulin class switching or class switch recombination
(CSR) is a natural biological process that alters a B cell's production of
antibodies (immunoglobulins) from one class to another. However, the mechanism of
CSR of Ig genes in cancer is still unknown. Here, we confirmed by detecting the
hallmark of CSR that the Igalpha gene in cancer underwent CSR. Then we focused on
activation-induced cytidine deaminase (AID), a crucial factor for initiating CSR.
Further studies using tumor necrosis factor (TNF)-alpha stimulation and specific
inhibitor of NF-kappaB revealed that TNF-alpha could increase AID expression
through NF-kappaB signaling. Finally, we demonstrated that AID could co-localize
with protein kinase A and bind to the switching (Salpha) region of the Igalpha
gene. Overexpression of AID obviously enhanced Igalpha heavy chain expression and
its binding ability to the Salpha region. These findings indicated that TNF-alpha
induced AID expression is involved with CSR in cancer.
PMID- 25849123
TI - Tassel removal positively affects biomass production coupled with significantly
increasing stem digestibility in switchgrass.
AB - In this study, tassels of Cave-in-Rock (upland) and Alamo (lowland) were removed
at or near tassel emergence to explore its effects on biomass production and
quality. Tassel-removed (TR) Cave-in-Rock and Alamo both exhibited a significant
(P<0.05) increase in plant heights (not including tassel length), tiller number,
and aboveground biomass dry weight (10% and 12%, 30% and 13%, 13% and 18%,
respectively by variety) compared to a control (CK) treatment. Notably, total
sugar yields of TR Cave-in-Rock and Alamo stems increased significantly (P<0.05
or 0.01) by 19% and 19%, 21% and 14%, 52% and 18%, respectively by variety,
compared to those of control switchgrass under 3 treatments by direct enzymatic
hydrolysis (DEH), enzymatic hydrolysis after 1% NaOH pretreatment (EHAL) and
enzymatic hydrolysis after 1% H2SO4 pretreatment (EHAC). These differences were
mainly due to significantly (P<0.05 or 0.01) higher cellulose content, lower
cellulose crystallinity indexes (CrI) caused by higher arabinose (Ara)
substitution in xylans, and lower S/G ratio in lignin. However, the increases of
nitrogen (N) and sulphur (S) concentration negatively affects the combustion
quality of switchgrass aboveground biomass. This work provides information for
increasing biomass production and quality in switchgrass and also facilitates the
inhibition of gene dispersal of switchgrass in China.
PMID- 25849124
TI - Antibodies to group A streptococcal virulence factors, SIC and DRS, increase
predilection to GAS pyoderma.
AB - BACKGROUND: Streptococcus pyogenes (group A streptococcus; GAS) is an etiological
agent for pharyngitis, pyoderma, and invasive infections in humans. Pharyngitis
and pyoderma may lead to serious immune sequelae such as rheumatic heart disease
and post-streptococcal glomerulonephritis (PSGN). Streptococcal Inhibitor of
Complement (SIC) and its orthologue, distantly related to SIC (DRS), are
virulence factors expressed by only four of more than 100 M types of GAS. These
four types (M1, M57, M12 and M55) are among the M types, which are associated
with PSGN. In several populations PSGN has been shown to be a risk factor for
chronic kidney disease (CKD) and end-stage renal disease (ESRD). Previous studies
showed SIC or DRS antibody-prevalence was associated with PSGN, and
seroprevalence of SIC antibodies is significantly high among CKD and ESRD
patients in Mumbai. METHODS: Streptococcal isolates recovered from GAS pyoderma
cases were typed. Seropositivity for SIC and DRS antibodies in subjects with
pyoderma, PSGN pediatric cases, age matched healthy controls and non-GAS pyoderma
cases were determined. RESULTS: We confirm in this study an association between
seroprevalence to SIC and DRS antibodies, and PSGN in Mumbai population despite
low point prevalence of M1, M12, M55 and M57. In addition we extended the study
to GAS-pyoderma and non-GAS pyoderma cases. To our surprise, we found a positive
association between the seroprevalence to SIC and DRS antibodies, and GAS
pyoderma owing to infection with diverse M types. The mechanism of increased
predisposition to pyoderma owing to infection by diverse GAS among SIC or DRS
antibody-positive population is not clear. Nonetheless, our findings could be
explained by a phenomenon akin to antibody-dependent enhancement (ADE).
CONCLUSIONS: This is the first report showing a small number of GAS M types
conferring predisposition to pyoderma by diverse types. Implications of this ADE
like phenomenon are discussed in the light of evolutionary advantage to GAS,
vaccine design and control of renal diseases.
PMID- 25849125
TI - Early modern humans and morphological variation in Southeast Asia: fossil
evidence from Tam Pa Ling, Laos.
AB - Little is known about the timing of modern human emergence and occupation in
Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by
at least 60 ka is supported by archaeological, paleogenetic and
paleoanthropological data. Recent discoveries in Laos, a modern human cranium
(TPL1) from Tam Pa Ling's cave, provided the first evidence for the presence of
early modern humans in mainland Southeast Asia by 63-46 ka. In the current study,
a complete human mandible representing a second individual, TPL 2, is described
using discrete traits and geometric morphometrics with an emphasis on determining
its population affinity. The TPL2 mandible has a chin and other discrete traits
consistent with early modern humans, but it retains a robust lateral corpus and
internal corporal morphology typical of archaic humans across the Old World. The
mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest
that a large range of morphological variation was present in early modern human
populations residing in the eastern Eurasia by MIS 3.
PMID- 25849127
TI - Correction: the EJC binding and dissociating activity of PYM is regulated in
Drosophila.
PMID- 25849126
TI - Hybrid polymer-lipid films as platforms for directed membrane protein insertion.
AB - Hybrids composed of amphiphilic block copolymers and lipids constitute a new
generation of biological membrane-inspired materials. Hybrid membranes resulting
from self-assembly of lipids and polymers represent adjustable models for
interactions between artificial and natural membranes, which are of key
importance, e.g., when developing systems for drug delivery. By combining
poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) amphiphilic copolymers
(PDMS-b-PMOXA) with various phospholipids, we obtained hybrid films with
modulated properties and topology, based on phase separation, and the formation
of distinct domains. By understanding the factors driving the phase separation in
these hybrid lipid-polymer films, we were able to use them as platforms for
directed insertion of membrane proteins. Tuning the composition of the polymer
lipids mixtures favored successful insertion of membrane proteins with desired
topological distributions (in polymer or/and lipid regions). Controlled insertion
and location of membrane proteins in hybrid films make these hybrids ideal
candidates for numerous applications where specific spatial functionality is
required.
PMID- 25849128
TI - Adverse life events and allele-specific methylation of the serotonin transporter
gene (SLC6A4) in adolescents: the TRAILS study.
AB - OBJECTIVES: Adverse life events increase vulnerability to affective disorders
later in life, possibly mediated by methylation of the serotonin transporter gene
(SLC6A4). We investigated the relationship of SLC6A4 methylation with various
types of adversity (perinatal adversity, traumatic youth experiences and
stressful life events [SLEs]), as well as with the timing of SLEs (during
childhood [0-11 years] or during adolescence [12-15 years]). In addition, we
investigated whether different serotonin-transporter-linked polymorphic region
genotypes were equally sensitive to SLE-related methylation. METHODS: In a
population sample of 939 adolescents (mean age = 16.2 years), we assessed SLC6A4
methylation, SLC6A4 functionality (serotonin-transporter-linked polymorphic
region "long" and "short" alleles, and rs25531), and adverse life events.
RESULTS: Only a higher number of SLEs was positively associated with higher
SLC6A4 methylation (B = 0.11, p = .011). Adolescent SLEs were associated with
higher SLC6A4 methylation (B = 0.13, p = .004) independently of childhood SLEs (B
= 0.02, p = .57). L-allele homozygotes showed a greater impact of SLEs on
methylation (B = 0.37, p < .001) than did s-allele carriers (B = 0.04, p = .66),
resulting in higher levels of SLC6A4 methylation for l-allele homozygotes among
those experiencing high levels of SLEs. CONCLUSIONS: Our findings demonstrate a
higher level of SLC6A4 methylation after SLEs in adolescents, with a more
pronounced association for SLEs during adolescence than during childhood.
Considering the allele-specific sensitivity of SLC6A4 methylation to SLEs, this
study may help clarify the role of SLC6A4 in the development of affective
disorders.
PMID- 25849129
TI - Longitudinal associations between depression, anxiety, pain, and pain-related
disability in chronic pain patients.
AB - OBJECTIVE: The current study sets out to examine the longitudinal relationship
between pain, pain-related disability, and symptoms of depression and anxiety.
The latter symptoms are highly prevalent in chronic pain and seriously impede
functioning and quality of life. Nevertheless, the direction of the relationship
involving these variables among individuals with chronic pain is still unclear.
METHODS: Four-hundred twenty-eight individuals with chronic pain (238 women, mean
age 54.84 years, mean pain duration 85.21 months) treated at two pain clinics
completed questionnaires regarding their pain (Short-Form McGill Pain
Questionnaire), depression (Center for Epidemiological Studies-Depression Scale),
state anxiety (State-Trait Anxiety Inventory), and pain-related disability (Pain
Disability Index) at four time points, with an average of 5 months between
measurements. Cross-lagged, structural equation modeling analyses were performed,
enabling the examination of longitudinal associations between the variables.
RESULTS: Significant symptoms of both depression and anxiety were reported by
more than half of the sample on all waves. A latent depression/anxiety variable
longitudinally predicted pain (beta = .27, p < .001) and pain-related disability
(beta = .38, p < .001). However, neither pain (beta = .10, p = .126) nor pain
related disability (beta = -.01, p = .790) predicted depression/anxiety.
CONCLUSIONS: Among adult patients with chronic pain treated at specialty pain
clinics, high levels of depression and anxiety may worsen pain and pain-related
disability.
PMID- 25849130
TI - Studying clonal dynamics in response to cancer therapy using high-complexity
barcoding.
AB - Resistance to cancer therapies presents a significant clinical challenge. Recent
studies have revealed intratumoral heterogeneity as a source of therapeutic
resistance. However, it is unclear whether resistance is driven predominantly by
pre-existing or de novo alterations, in part because of the resolution limits of
next-generation sequencing. To address this, we developed a high-complexity
barcode library, ClonTracer, which enables the high-resolution tracking of more
than 1 million cancer cells under drug treatment. In two clinically relevant
models, ClonTracer studies showed that the majority of resistant clones were part
of small, pre-existing subpopulations that selectively escaped under therapeutic
challenge. Moreover, the ClonTracer approach enabled quantitative assessment of
the ability of combination treatments to suppress resistant clones. These
findings suggest that resistant clones are present before treatment, which would
make up-front therapeutic combinations that target non-overlapping resistance a
preferred approach. Thus, ClonTracer barcoding may be a valuable tool for
optimizing therapeutic regimens with the goal of curative combination therapies
for cancer.
PMID- 25849131
TI - Resveratrol activates duodenal Sirt1 to reverse insulin resistance in rats
through a neuronal network.
AB - Resveratrol improves insulin sensitivity and lowers hepatic glucose production
(HGP) in rat models of obesity and diabetes, but the underlying mechanisms for
these antidiabetic effects remain elusive. One process that is considered a key
feature of resveratrol action is the activation of the nicotinamide adenine
dinucleotide (NAD(+))-dependent deacetylase sirtuin 1 (SIRT1) in various tissues.
However, the low bioavailability of resveratrol raises questions about whether
the antidiabetic effects of oral resveratrol can act directly on these tissues.
We show here that acute intraduodenal infusion of resveratrol reversed a 3 d high
fat diet (HFD)-induced reduction in duodenal-mucosal Sirt1 protein levels while
also enhancing insulin sensitivity and lowering HGP. Further, we found that
duodenum-specific knockdown of Sirt1 expression for 14 d was sufficient to induce
hepatic insulin resistance in rats fed normal chow. We also found that the
glucoregulatory role of duodenally acting resveratrol required activation of
Sirt1 and AMP-activated protein kinase (Ampk) in this tissue to initiate a gut
brain-liver neuronal axis that improved hypothalamic insulin sensitivity and in
turn, reduced HGP. In addition to the effects of duodenally acting resveratrol in
an acute 3 d HFD-fed model of insulin resistance, we also found that short-term
infusion of resveratrol into the duodenum lowered HGP in two other rat models of
insulin resistance--a 28 d HFD-induced model of obesity and a nicotinamide (NA)
streptozotocin (STZ)-HFD-induced model of mild type 2 diabetes. Together, these
studies highlight the therapeutic relevance of targeting duodenal SIRT1 to
reverse insulin resistance and improve glucose homeostasis in obesity and
diabetes.
PMID- 25849132
TI - An RNAi therapeutic targeting antithrombin to rebalance the coagulation system
and promote hemostasis in hemophilia.
AB - Hemophilia A and B are inherited bleeding disorders characterized by deficiencies
in procoagulant factor VIII (FVIII) or factor IX (FIX), respectively. There
remains a substantial unmet medical need in hemophilia, especially in patients
with inhibitory antibodies against replacement factor therapy, for novel and
improved therapeutic agents that can be used prophylactically to provide
effective hemostasis. Guided by reports suggesting that co-inheritance of
prothrombotic mutations may ameliorate the clinical phenotype in hemophilia, we
developed an RNA interference (RNAi) therapeutic (ALN-AT3) targeting antithrombin
(AT) as a means to promote hemostasis in hemophilia. When administered
subcutaneously, ALN-AT3 showed potent, dose-dependent, and durable reduction of
AT levels in wild-type mice, mice with hemophilia A, and nonhuman primates
(NHPs). In NHPs, a 50% reduction in AT levels was achieved with weekly dosing at
approximately 0.125 mg/kg, and a near-complete reduction in AT levels was
achieved with weekly dosing at 1.5 mg/kg. Treatment with ALN-AT3 promoted
hemostasis in mouse models of hemophilia and led to improved thrombin generation
in an NHP model of hemophilia A with anti-factor VIII inhibitors. This
investigational compound is currently in phase 1 clinical testing in subjects
with hemophilia A or B.
PMID- 25849133
TI - Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose
production in rats.
AB - Metformin is a first-line therapeutic option for the treatment of type 2
diabetes, even though its underlying mechanisms of action are relatively unclear.
Metformin lowers blood glucose levels by inhibiting hepatic glucose production
(HGP), an effect originally postulated to be due to a hepatic AMP-activated
protein kinase (AMPK)-dependent mechanism. However, studies have questioned the
contribution of hepatic AMPK to the effects of metformin on lowering
hyperglycemia, and a gut-brain-liver axis that mediates intestinal nutrient- and
hormone-induced lowering of HGP has been identified. Thus, it is possible that
metformin affects HGP through this inter-organ crosstalk. Here we show that
intraduodenal infusion of metformin for 50 min activated duodenal mucosal Ampk
and lowered HGP in a rat 3 d high fat diet (HFD)-induced model of insulin
resistance. Inhibition of duodenal Ampk negated the HGP-lowering effect of
intraduodenal metformin, and both duodenal glucagon-like peptide-1 receptor (Glp
1r)-protein kinase A (Pka) signaling and a neuronal-mediated gut-brain-liver
pathway were required for metformin to lower HGP. Preabsorptive metformin also
lowered HGP in rat models of 28 d HFD-induced obesity and insulin resistance and
nicotinamide (NA)-streptozotocin (STZ)-HFD-induced type 2 diabetes. In an
unclamped setting, inhibition of duodenal Ampk reduced the glucose-lowering
effects of a bolus metformin treatment in rat models of diabetes. These findings
show that, in rat models of both obesity and diabetes, metformin activates a
previously unappreciated duodenal Ampk-dependent pathway to lower HGP and plasma
glucose levels.
PMID- 25849134
TI - Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T
lymphocytes.
AB - Adoptive transfer of chimeric antigen receptor (CAR)-redirected T lymphocytes
(CAR-T cells) has had less striking therapeutic effects in solid tumors than in
lymphoid malignancies. Although active tumor-mediated immunosuppression may have
a role in limiting the efficacy of CAR-T cells, functional changes in T
lymphocytes after their ex vivo manipulation may also account for the reduced
ability of cultured CAR-T cells to penetrate stroma-rich solid tumors compared
with lymphoid tissues. We therefore studied the capacity of human in vitro
cultured CAR-T cells to degrade components of the extracellular matrix (ECM). In
contrast to freshly isolated T lymphocytes, we found that in vitro-cultured T
lymphocytes lack expression of the enzyme heparanase (HPSE), which degrades
heparan sulfate proteoglycans, the main components of ECM. We found that HPSE
mRNA is downregulated in in vitro-expanded T cells, which may be a consequence of
p53 (officially known as TP53, encoding tumor protein 53) binding to the HPSE
gene promoter. We therefore engineered CAR-T cells to express HPSE and showed
their improved capacity to degrade the ECM, which promoted tumor T cell
infiltration and antitumor activity. The use of this strategy may enhance the
activity of CAR-T cells in individuals with stroma-rich solid tumors.
PMID- 25849136
TI - Interactions between Heterogeneous Uptake and Adsorption of Sulfur Dioxide and
Acetaldehyde on Hematite.
AB - Sulfur dioxide and organic aldehydes in the atmosphere are ubiquitous and often
correlated with mineral dust aerosols. Heterogeneous uptake and adsorption of one
of these species on mineral aerosols can potentially change the properties of the
particles and further affect the subsequent heterogeneous reactions of the other
species on the coating particles. In this study, the interactions between
heterogeneous uptake and adsorption of sulfur dioxide and acetaldehyde on
hematite are investigated by using in situ diffuse-reflectance infrared Fourier
transform spectroscopy (DRIFTS) at room temperature. It is found that the
preadsorption of SO2 on alpha-Fe2O3 can significantly hinder the subsequent
heterogeneous oxidation of CH3CHO to acetate, while the preadsorption of CH3CHO
significantly suppresses the heterogeneous reaction of large amounts of SO2 on
the surface of alpha-Fe2O3 and has a little influence on the uptake of small
amount of SO2. The heterogeneous reactions of SO2 on alpha-Fe2O3 preadsorbed by
CH3CHO change the existing acetate on the particle surface into chemisorbed
acetic acid, for the enhancement of surface acidity after the uptake of SO2.
During these processes, different surface hydroxyl groups showed different
reactivities. Atmospheric implications of this study are discussed.
PMID- 25849137
TI - Orbital Decompression for Compressive Optic Neuropathy in Patients with a
Metastatic Orbital Tumor from Breast Carcinoma.
AB - We report two patients who underwent orbital decompression for compressive optic
neuropathy due to a metastatic orbital tumor from breast cancer. One patient was
a 47-year-old woman with right compressive optic neuropathy. Balanced orbital
decompression was performed 11 days after her first visit. At postoperative week
1, her right visual acuity and critical flicker frequency value had improved from
0.1 and 20 Hz to 1.0 and 35 Hz, respectively, and good vision was maintained at 6
months postoperatively. The other patient was a 61-year-old woman with right
compressive optic neuropathy. Medial orbital wall decompression was performed 5
days after her first visit. Her right visual acuity and critical flicker
frequency values improved until 38 days after the surgery, from 0.5 and 19 Hz to
1.2 and 31 Hz, respectively, with stable good vision for the following 6 months.
PMID- 25849135
TI - Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic
leukemia and breast cancer.
AB - A common key regulator of oncogenic signaling pathways in multiple tumor types is
the unique isomerase Pin1. However, available Pin1 inhibitors lack the required
specificity and potency for inhibiting Pin1 function in vivo. By using mechanism
based screening, here we find that all-trans retinoic acid (ATRA)--a therapy for
acute promyelocytic leukemia (APL) that is considered the first example of
targeted therapy in cancer, but whose drug target remains elusive--inhibits and
degrades active Pin1 selectively in cancer cells by directly binding to the
substrate phosphate- and proline-binding pockets in the Pin1 active site. ATRA
induced Pin1 ablation degrades the protein encoded by the fusion oncogene PML
RARA and treats APL in APL cell and animal models as well as in human patients.
ATRA-induced Pin1 ablation also potently inhibits triple-negative breast cancer
cell growth in human cells and in animal models by acting on many Pin1 substrate
oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple Pin1
regulated cancer-driving pathways, an attractive property for treating aggressive
and drug-resistant tumors.
PMID- 25849139
TI - Aspartic acid based nucleoside phosphoramidate prodrugs as potent inhibitors of
hepatitis C virus replication.
AB - In view of a persistent threat to mankind, the development of nucleotide-based
prodrugs against hepatitis C virus (HCV) is considered as a constant effort in
many medicinal chemistry groups. In an attempt to identify novel nucleoside
phosphoramidate analogues for improving the anti-HCV activity, we have explored,
for the first time, aspartic acid (Asp) and iminodiacetic acid (IDA) esters as
amidate counterparts by considering three 2'-C-methyl containing nucleosides, 2'
C-Me-cytidine, 2'-C-Me-uridine and 2'-C-Me-2'-fluoro-uridine. Synthesis of these
analogues required protection for the vicinal diol functionality of the sugar
moiety and the amino group of the cytidine nucleoside to regioselectively perform
phosphorylation reaction at the 5'-hydroxyl group. Anti-HCV data demonstrate that
the Asp-based phosphoramidates are ~550 fold more potent than the parent
nucleosides. The inhibitory activity of the Asp-ProTides was higher than the Ala
ProTides, suggesting that Asp would be a potential amino acid candidate to be
considered for developing novel antiviral prodrugs.
PMID- 25849140
TI - Uniform sampling of steady states in metabolic networks: heterogeneous scales and
rounding.
AB - The uniform sampling of convex polytopes is an interesting computational problem
with many applications in inference from linear constraints, but the performances
of sampling algorithms can be affected by ill-conditioning. This is the case of
inferring the feasible steady states in models of metabolic networks, since they
can show heterogeneous time scales. In this work we focus on rounding procedures
based on building an ellipsoid that closely matches the sampling space, that can
be used to define an efficient hit-and-run (HR) Markov Chain Monte Carlo. In this
way the uniformity of the sampling of the convex space of interest is rigorously
guaranteed, at odds with non markovian methods. We analyze and compare three
rounding methods in order to sample the feasible steady states of metabolic
networks of three models of growing size up to genomic scale. The first is based
on principal component analysis (PCA), the second on linear programming (LP) and
finally we employ the Lovazs ellipsoid method (LEM). Our results show that a
rounding procedure dramatically improves the performances of the HR in these
inference problems and suggest that a combination of LEM or LP with a subsequent
PCA perform the best. We finally compare the distributions of the HR with that of
two heuristics based on the Artificially Centered hit-and-run (ACHR), gpSampler
and optGpSampler. They show a good agreement with the results of the HR for the
small network, while on genome scale models present inconsistencies.
PMID- 25849138
TI - Flavin-containing monooxygenase 3 as a potential player in diabetes-associated
atherosclerosis.
AB - Despite the well-documented association between insulin resistance and
cardiovascular disease, the key targets of insulin relevant to the development of
cardiovascular disease are not known. Here, using non-biased profiling methods,
we identify the enzyme flavin-containing monooxygenase 3 (Fmo3) to be a target of
insulin. FMO3 produces trimethylamine N-oxide (TMAO), which has recently been
suggested to promote atherosclerosis in mice and humans. We show that FMO3 is
suppressed by insulin in vitro, increased in obese/insulin resistant male mice
and increased in obese/insulin-resistant humans. Knockdown of FMO3 in insulin
resistant mice suppresses FoxO1, a central node for metabolic control, and
entirely prevents the development of hyperglycaemia, hyperlipidemia and
atherosclerosis. Taken together, these data indicate that FMO3 is required for
FoxO1 expression and the development of metabolic dysfunction.
PMID- 25849141
TI - CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II
transcribed genes.
AB - Transcription through early-elongation checkpoints requires phosphorylation of
negative transcription elongation factors (NTEFs) by the cyclin-dependent kinase
(CDK) 9. Using CDK9 inhibitors and global run-on sequencing (GRO-seq), we have
mapped CDK9 inhibitor-sensitive checkpoints genome wide in human cells. Our data
indicate that early-elongation checkpoints are a general feature of RNA
polymerase (pol) II-transcribed human genes and occur independently of polymerase
stalling. Pol II that has negotiated the early-elongation checkpoint can elongate
in the presence of inhibitors but, remarkably, terminates transcription
prematurely close to the terminal polyadenylation (poly(A)) site. Our analysis
has revealed an unexpected poly(A)-associated elongation checkpoint, which has
major implications for the regulation of gene expression. Interestingly, the
pattern of modification of the C-terminal domain of pol II terminated at this new
checkpoint largely mirrors the pattern normally found downstream of the poly(A)
site, thus suggesting common mechanisms of termination.
PMID- 25849142
TI - Crystal structure of a light-driven sodium pump.
AB - Recently, the first known light-driven sodium pumps, from the microbial rhodopsin
family, were discovered. We have solved the structure of one of them,
Krokinobacter eikastus rhodopsin 2 (KR2), in the monomeric blue state and in two
pentameric red states, at resolutions of 1.45 A and 2.2 and 2.8 A, respectively.
The structures reveal the ion-translocation pathway and show that the sodium ion
is bound outside the protein at the oligomerization interface, that the ion
release cavity is capped by a unique N-terminal alpha-helix and that the ion
uptake cavity is unexpectedly large and open to the surface. Obstruction of the
cavity with the mutation G263F imparts KR2 with the ability to pump potassium.
These results pave the way for the understanding and rational design of cation
pumps with new specific properties valuable for optogenetics.
PMID- 25849143
TI - Structural mechanism of integrin inactivation by filamin.
AB - Activation of heterodimeric (alphabeta) integrin is crucial for regulating cell
adhesion. Binding of talin to the cytoplasmic face of integrin activates the
receptor, but how integrin is maintained in a resting state to counterbalance its
activation has remained obscure. Here, we report the structure of the cytoplasmic
domain of human integrin alphaIIbbeta3 bound to its inhibitor, the immunoglobin
repeat 21 of filamin A (FLNa-Ig21). The structure reveals an unexpected ternary
complex in which FLNa-Ig21 not only binds to the C terminus of the integrin beta3
cytoplasmic tail (CT), as previously predicted, but also engages N-terminal
helices of alphaIIb and beta3 CTs to stabilize an inter-CT clasp that helps
restrain the integrin in a resting state. Combined with functional data, the
structure reveals a new mechanism of filamin-mediated retention of inactive
integrin, suggesting a new framework for understanding regulation of integrin
activation and adhesion.
PMID- 25849144
TI - A lncRNA regulates alternative splicing via establishment of a splicing-specific
chromatin signature.
AB - Alternative pre-mRNA splicing is a highly cell type-specific process essential to
generating protein diversity. However, the mechanisms responsible for the
establishment and maintenance of heritable cell-specific alternative-splicing
programs are poorly understood. Recent observations point to a role of histone
modifications in the regulation of alternative splicing. Here we report a new
mechanism of chromatin-mediated splicing control involving a long noncoding RNA
(lncRNA). We have identified an evolutionarily conserved nuclear antisense
lncRNA, generated from within the human FGFR2 locus, that promotes epithelial
specific alternative splicing of FGFR2. The lncRNA acts through recruitment of
Polycomb-group proteins and the histone demethylase KDM2a to create a chromatin
environment that impairs binding of a repressive chromatin-splicing adaptor
complex important for mesenchymal-specific splicing. Our results uncover a new
function for lncRNAs in the establishment and maintenance of cell-specific
alternative splicing via modulation of chromatin signatures.
PMID- 25849145
TI - Induction of size-dependent breakdown of blood-milk barrier in lactating mice by
TiO2 nanoparticles.
AB - This study aims to investigate the potential nanotoxic effects of TiO2
nanoparticles (TNPs) to dams and pups during lactation period. TiO2 nanoparticles
are accumulated in mammary glands of lactating mice after i.v. administration.
This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight
junction of the blood-milk barrier as indicated by the loss of tight junction
proteins and the shedding of alveolar epithelial cells. Compared to larger TNPs
(50 nm), smaller ones (8 nm) exhibit a higher accumulation in mammary glands and
are more potent in causing perturbations to blood-milk barrier. An alarming
finding is that the smaller TNPs (8 nm) are transferred from dams to pups through
breastfeeding, likely through the disrupted blood-milk barrier. However, during
the lactation period, the nutrient quality of milk from dams and the early
developmental landmarks of the pups are not affected by above perturbations.
PMID- 25849146
TI - Spatiotemporal evolution of Calophaca (fabaceae) reveals multiple dispersals in
central Asian mountains.
AB - BACKGROUND: The Central Asian flora plays a significant role in Eurasia and the
Northern Hemisphere. Calophaca, a member of this flora, includes eight currently
recognized species, and is centered in Central Asia, with some taxa extending
into adjacent areas. A phylogenetic analysis of the genus utilizing nuclear
ribosomal ITS and plastid trnS-trnG and rbcL sequences was carried out in order
to confirm its taxonomic status and reconstruct its evolutionary history.
METHODOLOGY/PRINCIPAL FINDING: We employed BEAST Bayesian inference for dating,
and S-DIVA and BBM for ancestral area reconstruction, to study its spatiotemporal
evolution. Our results show that Calophacais monophyletic and nested within
Caragana. The divergence time of Calophaca is estimated at ca. 8.0 Ma, most
likely driven by global cooling and aridification, influenced by rapid uplift of
the Qinghai Tibet Plateau margins. CONCLUSIONS/SIGNIFICANCE: According to
ancestral area reconstructions, the genus most likely originated in the Pamir
Mountains, a global biodiversity hotspot and hypothesized Tertiary refugium of
many Central Asian plant lineages. Dispersals from this location are inferred to
the western Tianshan Mountains, then northward to the Tarbagatai Range, eastward
to East Asia, and westward to the Caucasus, Russia, and Europe. The
spatiotemporal evolution of Calophaca provides a case contributing to an
understanding of the flora and biodiversity of the Central Asian mountains and
adjacent regions.
PMID- 25849147
TI - Anatomical Authorities: On the Epistemological Exclusion of Trans-Surgical
Patients.
AB - American feminist health activists in the 1970s created representations of
genital anatomy intended to replace the abstracted images of biomedicine's
'modest witness,' with what Michelle Murphy has called the 'immodest witness,'
authority explicitly derived from personal and embodied experience. Decades
later, a feminist publication in the tradition of the immodest witness called
Femalia was adopted into the practice of an American surgeon specializing in
trans- genital sex reassignment surgery (GSRS). Based on ethnographic and textual
research, I show how oppositional claims to represent the 'natural' female body
one valued for its medical objectivity and the other for its feminist
subjectivity-effectively foreclosed these as modes of authority through which the
trans- patient might contribute to her surgical care. I argue that trans-
patients' double epistemological exclusion contributes to a broader asymmetry in
the use of patients' subjective reports in the everyday practice of GSRS and the
clinical research by which it is evaluated.
PMID- 25849148
TI - Probing the cis-arrangement of prototype tight junction proteins claudin-1 and
claudin-3.
AB - Claudins form a large family of TJ (tight junction) proteins featuring four
transmembrane segments (TM1-TM4), two extracellular loops, one intracellular loop
and intracellular N- and C-termini. They form continuous and branched TJ strands
by homo- or heterophilic interaction within the same membrane (cis-interaction)
and with claudins of the opposing lateral cell membrane (trans-interaction). In
order to clarify the molecular organization of TJ strand formation, we
investigated the cis-interaction of two abundant prototypic claudins. Human
claudin-1 and claudin-3, fused to ECFP or EYFP at the N- or C-terminus, were
expressed in the TJ-free cell line HEK (human embryonic kidney)-293. Using FRET
analysis, the proximity of claudin N- and C-termini integrated in homopolymeric
strands composed of claudin-3 or of heteropolymeric strands composed of claudin-1
and claudin-3 were determined. The main results are that (i) within homo- and
heteropolymers, the average distance between the cytoplasmic ends of the TM1s of
cis-interacting claudin molecules is shorter than the average distance between
their TM4s, and (ii) TM1 segments of neighbouring claudins are oriented towards
each other as the cytoplasmic end of TM1 is in close proximity to more other TM1
segments than TM4 is to other TM4 segments. The results indicate at least two
different cis-interaction interfaces within claudin-3 homopolymers as well as
within claudin-1/claudin-3 heteropolymers. The data provide novel insight into
the molecular TJ architecture consistent with a model with an antiparallel double
row cis-arrangement of classic claudin protomers within strands.
PMID- 25849149
TI - Fitness of Leishmania donovani parasites resistant to drug combinations.
AB - Drug resistance represents one of the main problems for the use of chemotherapy
to treat leishmaniasis. Additionally, it could provide some advantages to
Leishmania parasites, such as a higher capacity to survive in stress conditions.
In this work, in mixed populations of Leishmania donovani parasites, we have
analyzed whether experimentally resistant lines to one or two combined anti
leishmanial drugs better support the stress conditions than a susceptible line
expressing luciferase (Luc line). In the absence of stress, none of the
Leishmania lines showed growth advantage relative to the other when mixed at a
1:1 parasite ratio. However, when promastigotes from resistant lines and the Luc
line were mixed and exposed to different stresses, we observed that the resistant
lines are more tolerant of different stress conditions: nutrient starvation and
heat shock-pH stress. Further to this, we observed that intracellular amastigotes
from resistant lines present a higher capacity to survive inside the macrophages
than those of the control line. These results suggest that resistant parasites
acquire an overall fitness increase and that resistance to drug combinations
presents significant differences in their fitness capacity versus single-drug
resistant parasites, particularly in intracellular amastigotes. These results
contribute to the assessment of the possible impact of drug resistance on
leishmaniasis control programs.
PMID- 25849150
TI - Rank diversity of languages: generic behavior in computational linguistics.
AB - Statistical studies of languages have focused on the rank-frequency distribution
of words. Instead, we introduce here a measure of how word ranks change in time
and call this distribution rank diversity. We calculate this diversity for books
published in six European languages since 1800, and find that it follows a
universal lognormal distribution. Based on the mean and standard deviation
associated with the lognormal distribution, we define three different word
regimes of languages: "heads" consist of words which almost do not change their
rank in time, "bodies" are words of general use, while "tails" are comprised by
context-specific words and vary their rank considerably in time. The heads and
bodies reflect the size of language cores identified by linguists for basic
communication. We propose a Gaussian random walk model which reproduces the rank
variation of words in time and thus the diversity. Rank diversity of words can be
understood as the result of random variations in rank, where the size of the
variation depends on the rank itself. We find that the core size is similar for
all languages studied.
PMID- 25849151
TI - Negotiating agency in cases of intimate partner violence in Vietnam.
AB - Understandings of women's agency in cases of intimate partner violence (IPV) have
been dominated by an individualistic focus on help-seeking behaviour. The role of
children in influencing, enabling and restricting the decision-making processes
of their mothers has been largely ignored. We adopt biographical analytical
approaches to qualitative longitudinal data collected as part of the Young Lives
study to highlight the interdependency of women's and children's agency in
contexts of IPV in Vietnam. We illustrate how women's agency is both enabled and
constrained by their relationships with their children, as well as by wider
structural processes, and examine how gender and generation intersect. In
marginalised settings where few formal services exist or strong social norms
preclude women from accessing support, understanding these informal coping
strategies and the processes by which these are negotiated is essential for
developing more effective policy responses.
PMID- 25849152
TI - Footprints of middle ages kingdoms are still visible in the contemporary surname
structure of Spain.
AB - To assess whether the present-day geographical variability of Spanish surnames
mirrors historical phenomena occurred at the times of their introduction (13th
16th century), and to infer the possible effect of foreign immigration (about 11%
of present-day) on the observed patterns of diversity, we have analyzed the
frequency distribution of 33,753 unique surnames (tokens) occurring 51,419,788
times, according to the list of Spanish residents of the year 2008. Isonymy
measures and surname distances have been computed for, and between, the 47
mainland Spanish provinces and compared to a numerical classification of
corresponding language varieties spoken in Spain. The comparison of the two
bootstrap consensus trees, representing surname and linguistic variability,
suggests a similar picture; major clusters are located in the east (Aragon,
Cataluna, Valencia), and in the north of the country (Asturias, Galicia, Leon).
Remaining regions appear to be considerably homogeneous. We interpret this
pattern as the long-lasting effect of the surname and linguistic normalization
actively led by the Christian kingdoms of the north (Reigns of Castilla y Leon
and Aragon) during and after the southwards reconquest (Reconquista) of the
territories ruled by the Arabs from the 8th century to the late 15th century,
that is when surnames became transmitted in a fixed way and when Castilian
linguistic varieties became increasingly prestigious and spread out. The
geography of contemporary surname and linguistic variability in Spain corresponds
to the political geography at the end of the Middle-Ages. The synchronicity
between surname adoption and the political and cultural effects of the
Reconquista have permanently forged a Spanish identity that subsequent
migrations, internal or external, did not deface.
PMID- 25849153
TI - Towards unraveling the human tooth transcriptome: the dentome.
AB - The goal of the study was to characterize the transcriptome profiles of human
ameloblasts and odontoblasts, evaluate molecular pathways and advance our
knowledge of the human "dentome". Laser capture microdissection was used to
isolate odontoblasts and ameloblasts from human tooth buds (15-20week gestational
age) from 4 fetuses. RNA was examined using Agilent 41k whole genome arrays at 2
different stages of enamel formation, presecretory and secretory. Probe detection
was considered against the array negative control to control for background
noise. Differential expression was examined using Significance Analysis of
Microarrays (SAM) 4.0 between different cell types and developmental stages with
a false discovery rate of 20%. Pathway analysis was conducted using Ingenuity
Pathway Analysis software. We found that during primary tooth formation,
odontoblasts expressed 14,802 genes, presecretory ameloblasts 15,179 genes and
secretory ameloblasts 14,526 genes. Genes known to be active during tooth
development for each cell type (eg COL1A1, AMELX) were shown to be expressed by
our approach. Exploring further into the list of differentially expressed genes
between the motile odontoblasts and non-motile presecretory ameloblasts we found
several genes of interest that could be involved in cell movement (FN1, LUM,
ASTN1). Furthermore, our analysis indicated that the Phospholipase C and ERK5
pathways, that are important for cell movement, were activated in the motile
odontoblasts. In addition our pathway analysis identified WNT3A and TGFB1 as
important upstream contributors. Recent studies implicate these genes in the
development of Schimke immuno-osseous dysplasia. The utility of laser capture
microdissection can be a valuable tool in the examination of specific tissues or
cell populations present in human tooth buds. Advancing our knowledge of the
human dentome and related molecular pathways provides new insights into the
complex mechanisms regulating odontogenesis and biomineralization. This knowledge
could prove useful in future studies of odontogenic related pathologies.
PMID- 25849154
TI - Enantioselective Arylative Dearomatization of Indoles via Pd-Catalyzed
Intramolecular Reductive Heck Reactions.
AB - A highly enantioselective intramolecular arylative dearomatization of indoles via
palladium-catalyzed reductive Heck reactions was developed. The new strategy led
to a series of optically active indolines bearing C2-quaternary stereocenters in
modest to good yields with excellent enantioselectivities (up to 99% ee).
PMID- 25849156
TI - A Comparison of the Perceptual and Technical Demands of Tennis Training,
Simulated Match Play, and Competitive Tournaments.
AB - PURPOSE: High-performance tennis environments aim to prepare athletes for
competitive demands through simulated-match scenarios and drills. With a dearth
of direct comparisons between training and tournament demands, the current
investigation compared the perceptual and technical characteristics of training
drills, simulated match play, and tournament matches. METHODS: Data were
collected from 18 high-performance junior tennis players (gender: 10 male, 8
female; age 16 +/- 1.1 y) during 6 +/- 2 drill-based training sessions, 5 +/- 2
simulated match-play sessions, and 5 +/- 3 tournament matches from each
participant. Tournament matches were further distinguished by win or loss and
against seeded or nonseeded opponents. Notational analysis of stroke and error
rates, winners, and serves, along with rating of perceived physical exertion
(RPE) and mental exertion was measured postsession. RESULTS: Repeated-measures
analyses of variance and effect-size analysis revealed that training sessions
were significantly shorter in duration than tournament matches (P < .05, d =
1.18). RPEs during training and simulated match-play sessions were lower than in
tournaments (P > .05; d = 1.26, d = 1.05, respectively). Mental exertion in
training was lower than in both simulated match play and tournaments (P > .05; d
= 1.10, d = 0.86, respectively). Stroke rates during tournaments exceeded those
observed in training (P < .05, d = 3.41) and simulated-match-play (P < .05, d =
1.22) sessions. Furthermore, the serve was used more during tournaments than
simulated match play (P < .05, d = 4.28), while errors and winners were similar
independent of setting (P > .05, d < 0.80). CONCLUSIONS: Training in the form of
drills or simulated match play appeared to inadequately replicate tournament
demands in this cohort of players. Coaches should be mindful of match demands to
best prescribe sessions of relevant duration, as well as internal (RPE) and
technical (stroke rate) load, to aid tournament preparation.
PMID- 25849155
TI - Histone chaperones in Arabidopsis and rice: genome-wide identification,
phylogeny, architecture and transcriptional regulation.
AB - BACKGROUND: Histone chaperones modulate chromatin architecture and hence play a
pivotal role in epigenetic regulation of gene expression. In contrast to their
animal and yeast counterparts, not much is known about plant histone chaperones.
To gain insights into their functions in plants, we sought to identify histone
chaperones from two model plant species and investigated their phylogeny, domain
architecture and transcriptional profiles to establish correlation between their
expression patterns and potential role in stress physiology and plant
development. RESULTS: Through comprehensive whole genome analyses of Arabidopsis
and rice, we identified twenty-two and twenty-five genes encoding histone
chaperones in these plants, respectively. These could be classified into seven
different families, namely NAP, CAF1, SPT6, ASF1, HIRA, NASP, and FACT.
Phylogenetic analyses of histone chaperones from diverse organisms including
representative species from each of the major plant groups, yeast and human
indicated functional divergence in NAP and CAF1C in plants. For the largest
histone chaperone family, NAP, phylogenetic reconstruction suggested the presence
of two distinct groups in plants, possibly with differing histone preferences.
Further, to comment upon their physiological roles in plants, we analyzed their
expression at different developmental stages, across various plant tissues, and
under biotic and abiotic stress conditions using pre-existing microarray and qRT
PCR. We found tight transcriptional regulation of some histone chaperone genes
during development in both Arabidopsis and rice, suggesting that they may play a
role in genetic reprogramming associated with the developmental process. Besides,
we found significant differential expression of a few histone chaperones under
various biotic and abiotic stresses pointing towards their potential function in
stress response. CONCLUSIONS: Taken together, our findings shed light onto the
possible evolutionary trajectory of plant histone chaperones and present novel
prospects about their physiological roles. Considering that the developmental
process and stress response require altered expression of a large array of genes,
our results suggest that some plant histone chaperones may serve a regulatory
role by controlling the expression of genes associated with these vital
processes, possibly via modulating chromatin dynamics at the corresponding
genetic loci.
PMID- 25849158
TI - Alternatives to conventional thermal treatments in fruit-juice processing. Part
1: Techniques and applications.
AB - This paper provides an overview of alternatives to conventional thermal
treatments and a review of the literature on fruit-juice processing for three key
operations in fruit-juice production such as microbial inactivation, enzyme
inactivation, and juice yield enhancement, these being radiation treatments (UV
light, high-intensity light pulses, gamma-irradiation), electrical treatments
(pulsed electric fields, radiofrequency electric fields, ohmic heating),
microwave heating, ultrasound, high hydrostatic pressure, inert gas treatments
(supercritical carbon dioxide, ozonation), and flash-vacuum expansion. The
nonthermal technologies discussed in this review have the potential to meet
industry and consumer expectations. However, the lack of standardization in
operating conditions hampers comparisons among different studies, and
consequently ambiguity arises within the literature. For the juice industry to
advance, more detailed studies are needed on the scaling-up, process design, and
optimization, as well as on the effect of such technologies on juice quality of
juices in order to maximize their potential as alternative nonthermal
technologies in fruit-juice processing.
PMID- 25849157
TI - Enhanced endogenous bone morphogenetic protein signaling protects against
bleomycin induced pulmonary fibrosis.
AB - BACKGROUND: Effective treatments for fibrotic diseases such as idiopathic
pulmonary fibrosis are largely lacking. Transforming growth factor beta (TGFbeta)
plays a central role in the pathophysiology of fibrosis. We hypothesized that
bone morphogenetic proteins (BMP), another family within the TGFbeta superfamily
of growth factors, modulate fibrogenesis driven by TGFbeta. We therefore studied
the role of endogenous BMP signaling in bleomycin induced lung fibrosis. METHODS:
Lung fibrosis was induced in wild-type or noggin haploinsufficient (Nog +/LacZ )
mice by intratracheal instillation of bleomycin, or phosphate buffered saline as
a control. Invasive pulmonary function tests were performed using the
flexiVent(r) SCIREQ system. The mice were sacrificed and lung tissue was
collected for analysis using histopathology, collagen quantification,
immunohistochemistry and gene expression analysis. RESULTS: Nog +/LacZ mice are a
known model of increased BMP signaling and were partially protected from
bleomycin-induced lung fibrosis with reduced Ashcroft score, reduced collagen
content and preservation of pulmonary compliance. In bleomycin-induced lung
fibrosis, TGFbeta and BMP signaling followed an inverse course, with dynamic
activation of TGFbeta signaling and repression of BMP signaling activity.
CONCLUSIONS: Upon bleomycin exposure, active BMP signaling is decreased.
Derepression of BMP signaling in Nog +/LacZ mice protects against bleomycin
induced pulmonary fibrosis. Modulating the balance between BMP and TGFbeta, in
particular increasing endogenous BMP signals, may therefore be a therapeutic
target in fibrotic lung disease.
PMID- 25849160
TI - Erbium hydroxide ethanedisulfonate: a cationic layered material with organic
anion exchange capability.
AB - We describe a cationic erbium-based material
[Er12(OH)29(H2O)5][O3SCH2CH2SO3]3.5.5H2O. As synthesized, the material is water
stable and capable of complete organic anion exchange for a variety of
alpha,omega-alkanedicarboxylates. We chose these anions as initial examples of
exchange and as an analog for pharmaceutical waste, some of which have a
carboxylate functionality at neutral pH range. Free-floating and partially
anchored organosulfonate anions reside between the cationic corrugated layers and
allow for exchange. The structure also displays a reversible hydration event
above 100 degrees C. Both the as-synthesized and the exchanged materials are
characterized by a variety of analytical techniques.
PMID- 25849159
TI - Psychological predictors of recovery from low back pain: a prospective study.
AB - BACKGROUND: Recovery from low back pain (LBP) is an important outcome for
patients and clinicians. Psychological factors are known to impact the course of
LBP but have not been extensively investigated for predicting recovery. The
purposes of this study were to: 1) describe LBP recovery rates at 6 months
following 4 weeks of physical therapy; 2) identify psychological factors
predictive of 6 month recovery status; and 3) identify psychological factors that
co-occur with 6 month recovery status. METHODS: This study was a secondary
analysis of a prospective cohort of patients (n = 111) receiving outpatient
physical therapy for LBP. Patients were administered the STarT Back Screening
Tool (SBT), individual psychological measures, a numerical pain rating scale
(NPRS) and Roland Morris Disability Questionnaire (RMDQ) at intake, 4-week, and 6
month assessments. LBP recovery was operationally defined based on meeting NPRS =
0/10 and RMDQ <= 2 criterion at 6-month follow-up assessment. Recovery groups
were then compared for differences on all variables at intake and on individual
psychological measures at 6-months. Discriminant function analysis (DFA)
identified which descriptive variables were predictive of recovery status.
RESULTS: The 6-month recovery rate was 14/111 (12.6%) for the combined NPRS and
RMDQ criterion. Non-recovered patients were associated with SBT risk status (p =
0.004), higher intake pain intensity (p = .008) and higher depressive symptoms (p
< .001) scores compared to recovered patients. The overall accuracy for intake
classification using DFA was 87.2% with SBT risk status, pain intensity, and
depressive symptoms all making unique contributions. At 6-months, non-recovered
patients had higher fear-avoidance, kinesiophobia, and depressive symptoms (p's <
.001) compared to recovered patients. The overall accuracy for 6-month
classification using DFA was 86.4% with fear-avoidance, kinesiophobia, and
depressive symptoms all making unique contributions. CONCLUSIONS: Our findings
indicated that psychological risk status, depressive symptoms, and pain intensity
were predictive of 6 month recovery status. Furthermore elevated fear-avoidance,
kinesiophobia, and depressive symptoms co-occurred with non-recovery at 6 months.
Future studies should investigate whether stratified psychologically informed
treatment options have the potential to improve recovery rates for those most at
risk for non-recovery.
PMID- 25849161
TI - In vitro antioxidant capacity and free radical scavenging evaluation of active
metabolite constituents of Newbouldia laevis ethanolic leaf extract.
AB - BACKGROUND: The aim of the present study was to evaluate the in vitro antioxidant
and free radical scavenging capacity of bioactive metabolites present in
Newbouldia laevis leaf extract. RESULTS: Chromatographic and spectrophotometric
methods were used in the study and modified where necessary in the study.
Bioactivity of the extract was determined at 10 MUg/ml, 50 MUg/ml, 100 MUg/ml,
200 MUg/ml and 400 MUg/ml concentrations expressed in % inhibition. The yield of
the ethanolic leaf extract of N.laevis was 30.3 g (9.93%). Evaluation of
bioactive metabolic constituents gave high levels of ascorbic acid (515.53 +/- 12
IU/100 g [25.7 mg/100 g]), vitamin E (26.46 +/- 1.08 IU/100 g), saponins (6.2 +/-
0.10), alkaloids (2.20 +/- 0.03), cardiac glycosides(1.48 +/- 0.22), amino acids
and steroids (8.01 +/- 0.04) measured in mg/100 g dry weight; moderate levels of
vitamin A (188.28 +/- 6.19 IU/100 g), tannins (0.09 +/- 0.30), terpenoids (3.42
+/- 0.67); low level of flavonoids (1.01 +/- 0.34 mg/100 g) and absence of
cyanogenic glycosides, carboxylic acids and aldehydes/ketones. The extracts
percentage inhibition of DPPH, hydroxyl radical (OH.), superoxide anion (O2 .-),
iron chelating, nitric oxide radical (NO), peroxynitrite (ONOO-), singlet oxygen
(1O2), hypochlorous acid (HOCl), lipid peroxidation (LPO) and FRAP showed a
concentration-dependent antioxidant activity with no significant difference with
the controls. Though, IC50 of the extract showed significant difference only in
singlet oxygen (1O2) and iron chelating activity when compared with the controls.
CONCLUSIONS: The extract is a potential source of antioxidants/free radical
scavengers having important metabolites which maybe linked to its ethno-medicinal
use.
PMID- 25849163
TI - Accurate Composite and Fragment-Based Quantum Chemical Models for Large
Molecules.
PMID- 25849166
TI - Abstraction: windows: Jeanne Rij-Rousseau.
PMID- 25849162
TI - The E3 ligase OsPUB15 interacts with the receptor-like kinase PID2 and regulates
plant cell death and innate immunity.
AB - BACKGROUND: Rice blast disease is one of the most destructive diseases of rice
worldwide. We previously cloned the rice blast resistance gene Pid2, which
encodes a transmembrane receptor-like kinase containing an extracellular B-lectin
domain and an intracellular serine/threonine kinase domain. However, little is
known about Pid2-mediated signaling. RESULTS: Here we report the functional
characterization of the U-box/ARM repeat protein OsPUB15 as one of the PID2
binding proteins. We found that OsPUB15 physically interacted with the kinase
domain of PID2 (PID2K) in vitro and in vivo and the ARM repeat domain of OsPUB15
was essential for the interaction. In vitro biochemical assays indicated that
PID2K possessed kinase activity and was able to phosphorylate OsPUB15. We also
found that the phosphorylated form of OsPUB15 possessed E3 ligase activity.
Expression pattern analyses revealed that OsPUB15 was constitutively expressed
and its encoded protein OsPUB15 was localized in cytosol. Transgenic rice plants
over-expressing OsPUB15 at early stage displayed cell death lesions spontaneously
in association with a constitutive activation of plant basal defense responses,
including excessive accumulation of hydrogen peroxide, up-regulated expression of
pathogenesis-related genes and enhanced resistance to blast strains. We also
observed that, along with plant growth, the cell death lesions kept spreading
over the whole seedlings quickly resulting in a seedling lethal phenotype.
CONCLUSIONS: These results reveal that the E3 ligase OsPUB15 interacts directly
with the receptor-like kinase PID2 and regulates plant cell death and blast
disease resistance.
PMID- 25849167
TI - Exome sequencing comes to the clinic.
PMID- 25849168
TI - How useful are screening tests?
PMID- 25849178
TI - A piece of my mind. The other generation.
PMID- 25849177
TI - Hospital credentialing and privileging of surgeons: a potential safety blind
spot.
PMID- 25849180
TI - Multiple blood pressure medications and mortality among elderly individuals.
PMID- 25849181
TI - Association between perioperative low-molecular-weight heparin vs unfractionated
heparin and clinical outcomes in patients with cancer undergoing surgery.
AB - CLINICAL QUESTION: In patients with cancer undergoing surgery, what is the
association between perioperative thromboprophylaxis with low-molecular-weight
heparin (LMWH) or unfractionated heparin and mortality, pulmonary embolism, deep
venous thrombosis, thrombocytopenia, and bleeding outcomes? BOTTOM LINE: When
used for perioperative thromboprophylaxis, there are no differences in the
association of LMWH vs unfractionated heparin for preventing mortality, pulmonary
embolism, deep venous thrombosis, bleeding outcomes, or thrombocytopenia in
patients with cancer.
PMID- 25849182
TI - Painful rash in a patient with bronchiectasis.
PMID- 25849183
TI - Patients with next-of-kin relationships outside the nuclear family.
PMID- 25849184
TI - Hypofractionated whole breast irradiation for early-stage breast cancer.
PMID- 25849185
TI - Low vs high glycemic index diet.
PMID- 25849186
TI - Hypofractionated whole breast irradiation for early-stage breast cancer--reply.
PMID- 25849187
TI - Low vs high glycemic index diet--reply.
PMID- 25849188
TI - Electronic health records and adolescent privacy.
PMID- 25849189
TI - Electronic health records and adolescent privacy--reply.
PMID- 25849190
TI - Incorrect absolute risk values.
PMID- 25849191
TI - Misspelled author name.
PMID- 25849192
TI - Incorrect author affiliation.
PMID- 25849179
TI - Association of type and location of BRCA1 and BRCA2 mutations with risk of breast
and ovarian cancer.
AB - IMPORTANCE: Limited information about the relationship between specific mutations
in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE: To identify
mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND
PARTICIPANTS: Observational study of women who were ascertained between 1937 and
2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2
mutations. The international sample comprised 19,581 carriers of BRCA1 mutations
and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6
continents. We estimated hazard ratios for breast and ovarian cancer based on
mutation type, function, and nucleotide position. We also estimated RHR, the
ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1
indicated elevated breast cancer risk; a value of RHR less than 1 indicated
elevated ovarian cancer risk. EXPOSURES: Mutations of BRCA1 or BRCA2. MAIN
OUTCOMES AND MEASURES: Breast and ovarian cancer risks. RESULTS: Among BRCA1
mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%)
with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%)
without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed
with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and
ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast
cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95%
CI, 1.22-1.74; P = 2 * 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01
1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P =
6 * 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from
c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P =
9 * 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1;
RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95%
CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69
3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249
to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44
0.60; P = 6 * 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR =
0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay
were associated with differential breast or ovarian cancer risks and an earlier
age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers.
CONCLUSIONS AND RELEVANCE: Breast and ovarian cancer risks varied by type and
location of BRCA1/2 mutations. With appropriate validation, these data may have
implications for risk assessment and cancer prevention decision making for
carriers of BRCA1 and BRCA2 mutations.
PMID- 25849194
TI - The care of the baby's eyes in the perambulator.
PMID- 25849196
TI - Mitochondrial tRNA-lookalikes in nuclear chromosomes: could they be functional?
AB - The presence in human nuclear chromosomes of multiple sequences that are highly
similar to human mitochondrial tRNAs (tRNA-lookalikes) raises intriguing
questions about the possible functionality of these genomic loci. In this
perspective, we explore the significance of the mitochondrial tRNA-lookalikes
based on a series of properties that argue for their non-accidental nature. We
particularly focus on the possibility of transcription as well as on potential
functional roles for these sequences that can range from their acting as DNA
regulatory elements to forming functional mature tRNAs or tRNA-derived fragments.
Extension of our analysis to other simians (chimp, gorilla, rhesus, and squirrel
monkey), 2 rodents (mouse and rat), a marsupial (opossum) and 3 invertebrates
(fruit-fly, worm, and sponge) revealed that mitochondrial tRNA-lookalikes are
prevalent in primates and the opossum but absent from the other analyzed
organisms.
PMID- 25849195
TI - The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo.
AB - A key step in generating planar cell polarity (PCP) is the formation of
restricted junctional domains containing Frizzled/Dishevelled/Diego (Fz/Dsh/Dgo)
or Van Gogh/Prickle (Vang/Pk) complexes within the same cell, stabilized via
Flamingo (Fmi) across cell membranes. Although models have been proposed for how
these complexes acquire and maintain their polarized localization, the machinery
involved in moving core PCP proteins around cells remains unknown. We describe
the AP-1 adaptor complex and Arf1 as major regulators of PCP protein trafficking
in vivo. AP-1 and Arf1 disruption affects the accumulation of Fz/Fmi and Vang/Fmi
complexes in the proximo-distal axis, producing severe PCP phenotypes. Using
novel tools, we demonstrate a direct and specific Arf1 involvement in Fz
trafficking in vivo. Moreover, we uncover a conserved Arf1 PCP function in
vertebrates. Our data support a model whereby the trafficking machinery plays an
important part during PCP establishment, promoting formation of polarized PCP
core complexes in vivo.
PMID- 25849197
TI - Smart functional nucleic acid chimeras: enabling tissue specific RNA targeting
therapy.
AB - A major obstacle for effective utilization of therapeutic oligonucleotides such
as siRNA, antisense, antimiRs etc. is to deliver them specifically to the target
tissues. Toward this goal, nucleic acid aptamers are re-emerging as a prominent
class of biomolecules capable of delivering target specific therapy and
therapeutic monitoring by various molecular imaging modalities. This class of
short oligonucleotide ligands with high affinity and specificity are selected
from a large nucleic acid pool against a molecular target of choice. Poor
cellular uptake of therapeutic oligonucleotides impedes gene-targeting efficacy
in vitro and in vivo. In contrast, aptamer-oligonucleotide chimeras have shown
the capacity to deliver siRNA, antimiRs, small molecule drugs etc. toward various
targets and showed very promising results in various studies on different
diseases models. However, to further improve the bio-stability of such chimeric
conjugates, it is important to introduce chemically-modified nucleic acid
analogs. In this review, we highlight the applications of nucleic acid aptamers
for target specific delivery of therapeutic oligonucleotides.
PMID- 25849200
TI - Improved Electrochemical Performance of Fe-Substituted NaNi0.5Mn0.5O2 Cathode
Materials for Sodium-Ion Batteries.
AB - A series of O3-phase NaFe(x)(Ni0.5Mn0.5)(1-x)O2 (x = 0, 0.1, 0.2, 0.3, 0.4, and
1) samples with different Fe contents was prepared and investigated as high
capacity cathodic hosts of Na-ion batteries. The partial substitution of Ni and
Mn with Fe in the O3-phase lattice can greatly improve the electrochemical
performance and the structural stability. A NaFe0.2Mn0.4Ni0.4O2 cathode with an
optimized Fe content of x = 0.2 can deliver an initial reversible capacity of 131
mAh g(-1), a reversible capacity greater than 95% over 30 cycles, and a high rate
capacity of 86 mAh g(-1) at 10 C in a voltage range of 2.0-4.0 V. The structural
characterizations reveal that pristine NaMn0.5Ni0.5O2 and Fe-substituted
NaFe0.2Mn0.4Ni0.4O2 lattices underwent different phase transformations from P3 to
P3" and from P3 to OP2 phases, respectively, at high voltage interval. The as
resulted OP2 phase by Fe substitution has smaller interslab distance (5.13 A)
than the P3" phase (5.72 A), which suppresses the co-insertion of the solvent
molecules, the electrolyte anions, or both and therefore enhances the cycling
stability in the high voltage charge. This finding suggests a new strategy for
creating cycle-stable transition-metal oxide cathodes for high-performance Na-ion
batteries.
PMID- 25849198
TI - Incomplete splicing of neutrophil-specific genes affects neutrophil development
in a zebrafish model of poikiloderma with neutropenia.
AB - Poikiloderma with neutropenia (PN) is a rare inherited disorder characterized by
poikiloderma, facial dysmorphism, pachyonychia, short stature and neutropenia.
The molecular testing of PN patients has identified mutations in the C16orf57
gene, which encodes a protein referred to as USB1 (U Six Biogenesis 1). In this
study, we developed a zebrafish model of PN by the microinjection of morpholino
antisense oligos to suppress usb1 gene function. Severe morphological defects,
including a bent tail, thin yolk extension and reduced body length, were
predominant in the Usb1-suppressed embryos (morphants). We also observed
significantly decreased number of neutrophils in the morphants by Sudan Black
staining. Interestingly, the splicing of genes involved in neutrophil
differentiation and development, such as mpx, ncf1, ela3l and npsn, was aberrant
in the morphants. However, the splicing of haematopoietic precursors and
erythroid-specific genes was unaltered. Importantly, the neutrophil defects were
almost completely rescued by co-injection of ela3l mRNA, the most markedly
affected gene in the morphants. Our study demonstrated a possible role of USB1 in
modulating the tissue-specific gene splicing that eventually leads to the
impaired development of neutrophils. This zebrafish model could serve as a
valuable tool to investigate the causative role of USB1 in PN pathogenesis.
PMID- 25849199
TI - Domain movements during CCA-addition: a new function for motif C in the catalytic
core of the human tRNA nucleotidyltransferases.
AB - CCA-adding enzymes are highly specific RNA polymerases that synthesize and
maintain the sequence CCA at the tRNA 3'-end. This nucleotide triplet is a
prerequisite for tRNAs to be aminoacylated and to participate in protein
biosynthesis. During CCA-addition, a set of highly conserved motifs in the
catalytic core of these enzymes is responsible for accurate sequential nucleotide
incorporation. In the nucleotide binding pocket, three amino acid residues form
Watson-Crick-like base pairs to the incoming CTP and ATP. A reorientation of
these templating amino acids switches the enzyme's specificity from CTP to ATP
recognition. However, the mechanism underlying this essential structural
rearrangement is not understood. Here, we show that motif C, whose actual
function has not been identified yet, contributes to the switch in nucleotide
specificity during polymerization. Biochemical characterization as well as EPR
spectroscopy measurements of the human enzyme reveal that mutating the highly
conserved amino acid position D139 in this motif interferes with AMP
incorporation and affects interdomain movements in the enzyme. We propose a model
of action, where motif C forms a flexible spring element modulating the relative
orientation of the enzyme's head and body domains to accommodate the growing 3'
end of the tRNA. Furthermore, these conformational transitions initiate the
rearranging of the templating amino acids to switch the specificity of the
nucleotide binding pocket from CTP to ATP during CCA-synthesis.
PMID- 25849201
TI - Conformational Preadjustment in Aqueous Claisen Rearrangement Revealed by SITS
QM/MM MD Simulations.
AB - An efficient sampling method was implemented in QM/MM hybrid molecular
simulations to study aliphatic Claisen rearrangement in aqueous solutions. On the
basis of the computational results, the necessary conformational adjustment to
trap the reactant into a favorable compact conformation specifically in water was
observed. The conformational equilibrium was shown to be important to the
elucidation of the "water-acceleration" effect of Claisen rearrangement. Thus, a
two-step process of aqueous Claisen rearrangement was proposed. It was similar to
the pseudodiaxial-pseudodiequatorial conformational equilibrium observed in the
enzymatic reaction of chorismate acid but with explicit inclusion of the solvent
coordinates to explain the solvation effects. Polarization was found to occur
during the reactant conformational transition. A solvent with high cohesive
energy density (CED) like water was suggested to accommodate compact conformers
better, thus facilitating the following reaction by concentrating the real
"active" reactant. The substituent effects also manifested, leading to varied
conformational distributions of different substituted allyl vinyl ethers (AVEs).
The application of the enhanced sampling method allowed a systematic analysis of
thermodynamic information without loss of solvent coordinates. These data showed
the conformational transition of AVEs was an entropy-driving process which was
sensitive to the substituent, and enthalpy played an important role in the
solvation effect on the conformational equilibrium.
PMID- 25849202
TI - The global inventor gap: distribution and equality of world-wide inventive
effort, 1990-2010.
AB - Applying distance-to-frontier analysis, we have used 2.9 million patents and
population data to assess whether the relative capacity of world countries and
major regions to create new knowledge and technology has become globally more
equal or less equal between 1990 and 2010. We show with the Gini coefficient that
the global distribution of inventors has become more equal between major
countries and regions. However, this trend has been largely due to the improved
performance of only two major countries, China and India. The worst performing
regions, totalling a population of almost 2 billion, are actually falling behind.
Our results suggest that substantial parts of the global population have fallen
further behind countries at the global frontier in their ability to create new
knowledge and inventions, and that the catch-up among the least developed and
middle-income countries is highly uneven, prompting questions about the nature
and future of the global knowledge economy.
PMID- 25849204
TI - Does interdisciplinary and multiprofessional undergraduate education increase
students' self-confidence and knowledge toward palliative care? Evaluation of an
undergraduate curriculum design for palliative care at a German academic
hospital.
AB - BACKGROUND: Undergraduate palliative care education (UPCE) became mandatory in
Germany by 2013. The training in Mainz, addressing fifth-year (5Y) medical
students, emphasizes transfer of knowledge and skills. In this study we assessed
students' knowledge and students' self-estimation of self-confidence in
palliative care (PC) according to Bandura's concept of self-efficacy. OBJECTIVE:
The study objective was to evaluate the effects of the Mainz UPCE on students'
self-confidence regarding important domains in PC. METHODS: We conducted a
prospective questionnaire-based cohort study with a pre-post design. 5Y medical
students (n=329) were asked for self-estimation concerning knowledge, somatic
aspects, spiritual and psychological aspects before and after a 7x90-minute
teaching course. To assess knowledge, students completed a multiple choice
examination at the end of the term. RESULTS: Overall, 156 students completed
matched surveys at both points of measurement. The majority of these students
felt more confident after the course than before in all aspects of PC (p<0.0001).
All students passed the exam with average scores greater than 90%. CONCLUSION: A
7x90-minute interactive tutorial in PC for 5Y medical students is feasible and
improves both self-efficacy and knowledge of core PC issues. Whether the effects
of the course are long-lasting is the objective for further research.
PMID- 25849205
TI - Doublecortin is widely expressed in the developing and adult retina of sharks.
AB - Doublecortin (DCX) is a microtubule-associated protein that has been considered a
marker for neuronal precursors and young migrating neurons during the development
of the central nervous system and in adult neurogenic niches. The retina of
fishes represents an accessible, continuously growing and highly structured
(layered) part of the central nervous system and, therefore, offers an
exceptional model to extend our knowledge on the possible role of DCX in
promoting neurogenesis and migration to appropriate layers. We have analyzed the
distribution of DCX in the embryonic and postembryonic retina of a small shark,
the lesser spotted dogfish Scyliorhinus canicula, by means of
immunohistochemistry. We investigated the relationship between DCX expression and
the neurogenic state of DCX-labeled cells by exploring its co-localization with
the proliferation marker PCNA (proliferating cell nuclear antigen) and the marker
of neuronal differentiation HuC/D. Since radially migrating neurons use radial
glial fibers as substrate, we explored the possible correlation between DCX
expression and cell migration along radial glia by comparing its expression with
that of the glial marker GFAP (glial fibrillary acidic protein). Additionally, we
characterized DCX-expressing cells by double immunocytochemistry using antibodies
against Calbindin (a marker for mature bipolar and horizontal cells in this
species) and Pax6, which has been proposed as a regulator of cell proliferation,
cell differentiation, and neuron diversification in the neural retina of sharks.
Strong DCX immunoreactivity was observed in immature cells and cell processes, at
a time when retinal cells were not yet organized into different laminae. DCX was
also found in subsets of mature ganglion, amacrine, bipolar and horizontal cells
long after they had exited the cell cycle, a pattern that was maintained in
juveniles and adults. Our results on DCX expression in the retina are compatible
with a role for DCX in cell migration within the immature retina, and in dynamic
neuronal plasticity in the mature retina. We also provide evidence of DCX
expression in discrete cells in the retinal pigment epithelium of prehatching
embryos and juveniles, which suggest that retinal pigmented epithelial cells in
sharks, as in mammals, have an intrinsic capacity to proliferate and
differentiate into cells with neural identity.
PMID- 25849206
TI - Cellular size as a means of tracking mTOR activity and cell fate of CD4+ T cells
upon antigen recognition.
AB - mTOR is a central integrator of metabolic and immunological stimuli, dictating
immune cell activation, proliferation and differentiation. In this study, we
demonstrate that within a clonal population of activated T cells, there exist
both mTORhi and mTORlo cells exhibiting highly divergent metabolic and
immunologic functions. By taking advantage of the role of mTOR activation in
controlling cellular size, we demonstrate that upon antigen recognition, mTORhi
CD4+ T cells are destined to become highly glycolytic effector cells. Conversely,
mTORlo T cells preferentially develop into long-lived cells that express high
levels of Bcl-2, CD25, and CD62L. Furthermore, mTORlo T cells have a greater
propensity to differentiate into suppressive Foxp3+ T regulatory cells, and this
paradigm was also observed in human CD4+ T cells. Overall, these studies provide
the opportunity to track the development of effector and memory T cells from
naive precursors, as well as facilitate the interrogation of immunologic and
metabolic programs that inform these fates.
PMID- 25849207
TI - ALV-J GP37 molecular analysis reveals novel virus-adapted sites and three
tyrosine-based Env species.
AB - Compared to other avian leukosis viruses (ALV), ALV-J primarily induces myeloid
leukemia and hemangioma and causes significant economic loss for the poultry
industry. The ALV-J Env protein is hypothesized to be related to its unique
pathogenesis. However, the molecular determinants of Env for ALV-J pathogenesis
are unclear. In this study, we compared and analyzed GP37 of ALV-J Env and the
EAV-HP sequence, which has high homology to that of ALV-J Env. Phylogenetic
analysis revealed five groups of ALV-J GP37 and two novel ALV-J Envs with endemic
GP85 and EAV-HP-like GP37. Furthermore, at least 15 virus-adapted mutations were
detected in GP37 compared to the EAV-HP sequence. Further analysis demonstrated
that three tyrosine-based motifs (YxxM, ITIM (immune tyrosine-based inhibitory
motif) and ITAM-like (immune tyrosine-based active motif like)) associated with
immune disease and oncogenesis were found in the cytoplasmic tail of GP37. Based
on the potential function and distribution of these motifs in GP37, ALV-J Env was
grouped into three species, inhibitory Env, bifunctional Env and active Env.
Accordingly, 36.91%, 61.74% and 1.34% of ALV-J Env sequences from GenBank are
classified as inhibitory, bifunctional and active Env, respectively.
Additionally, the Env of the ALV-J prototype strain, HPRS-103, and 17 of 18 EAV
HP sequences belong to the inhibitory Env. And models for signal transduction of
the three ALV-J Env species were predicted. Our findings and models provide novel
insights for identifying the roles and molecular mechanism of ALV-J Env in the
unique pathogenesis of ALV-J.
PMID- 25849208
TI - Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell
Transplantation Identifies Patients at Risk for Adverse Outcomes.
AB - Systems that evolve over time and follow mathematical laws as they evolve are
called dynamical systems. Lymphocyte recovery and clinical outcomes in 41
allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy
total body irradiation were studied to determine if immune reconstitution could
be described as a dynamical system. Survival, relapse, and graft-versus-host
disease (GVHD) were not significantly different in 2 cohorts of patients
receiving different doses of ATG. However, donor-derived CD3(+) cell
reconstitution was superior in the lower ATG dose cohort, and there were fewer
instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in
each individual over time and demonstrated 1 of 3 sigmoid growth patterns:
Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n =
14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor
lymphocyte reconstitution. There was a significant association between lymphocyte
recovery patterns and both the rate of change of donor-derived CD3(+) at day 30
after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed
more frequently with pattern A, relapse and DLI more so with pattern C, with a
consequent survival advantage in patients with patterns A and B. We conclude that
evaluating immune reconstitution after SCT as a dynamical system may
differentiate patients at risk of adverse outcomes and allow early intervention
to modulate that risk.
PMID- 25849209
TI - Balanced sparse model for tight frames in compressed sensing magnetic resonance
imaging.
AB - Compressed sensing has shown to be promising to accelerate magnetic resonance
imaging. In this new technology, magnetic resonance images are usually
reconstructed by enforcing its sparsity in sparse image reconstruction models,
including both synthesis and analysis models. The synthesis model assumes that an
image is a sparse combination of atom signals while the analysis model assumes
that an image is sparse after the application of an analysis operator. Balanced
model is a new sparse model that bridges analysis and synthesis models by
introducing a penalty term on the distance of frame coefficients to the range of
the analysis operator. In this paper, we study the performance of the balanced
model in tight frame based compressed sensing magnetic resonance imaging and
propose a new efficient numerical algorithm to solve the optimization problem. By
tuning the balancing parameter, the new model achieves solutions of three models.
It is found that the balanced model has a comparable performance with the
analysis model. Besides, both of them achieve better results than the synthesis
model no matter what value the balancing parameter is. Experiment shows that our
proposed numerical algorithm constrained split augmented Lagrangian shrinkage
algorithm for balanced model (C-SALSA-B) converges faster than previously
proposed algorithms accelerated proximal algorithm (APG) and alternating
directional method of multipliers for balanced model (ADMM-B).
PMID- 25849210
TI - Stoichiometric determination of nitrate fate in agricultural ecosystems during
rainfall events.
AB - Ecologists have found a close relationship between the concentrations of nitrate
(NO3-) and dissolved organic carbon (DOC) in ecosystems. However, it is difficult
to determine the NO3- fate exactly because of the low coefficient in the
constructed relationship. In the present paper, a negative power-function
equation (r(2) = 0.87) was developed by using 411 NO3- data points and DOC:NO3-
ratios from several agricultural ecosystems during different rainfall events. Our
analysis of the stoichiometric method reveals several observations. First, the
NO3- concentration demonstrated the largest changes when the DOC:NO3- ratio
increased from 1 to 10. Second, the biodegradability of DOC was an important
factor in controlling the NO3- concentration of agricultural ecosystems. Third,
sediment was important not only as a denitrification site, but also as a major
source of DOC for the overlying water. Fourth, a high DOC concentration was able
to maintain a low NO3- concentration in the groundwater. In conclusion, this new
stoichiometric method can be used for the accurate estimation and analysis of NO3
concentrations in ecosystems.
PMID- 25849211
TI - Submicroscopic and asymptomatic Plasmodium falciparum and Plasmodium vivax
infections are common in western Thailand - molecular and serological evidence.
AB - BACKGROUND: Malaria is a public health problem in parts of Thailand, where
Plasmodium falciparum and Plasmodium vivax are the main causes of infection. In
the northwestern border province of Tak parasite prevalence is now estimated to
be less than 1% by microscopy. Nonetheless, microscopy is insensitive at low
level parasitaemia. The objective of this study was to assess the current
epidemiology of falciparum and vivax malaria in Tak using molecular methods to
detect exposure to and infection with parasites; in particular, the prevalence of
asymptomatic infections and infections with submicroscopic parasite levels.
METHODS: Three-hundred microlitres of whole blood from finger-prick were
collected into capillary tubes from residents of a sentinel village and from
patients at a malaria clinic. Pelleted cellular fractions were screened by
quantitative PCR to determine parasite prevalence, while plasma was probed on a
protein microarray displaying hundreds of P. falciparum and P. vivax proteins to
obtain antibody response profiles in those individuals. RESULTS: Of 219 samples
from the village, qPCR detected 25 (11.4%) Plasmodium sp. infections, of which
92% were asymptomatic and 100% were submicroscopic. Of 61 samples from the clinic
patients, 27 (44.3%) were positive by qPCR, of which 25.9% had submicroscopic
parasite levels. Cryptic mixed infections, misdiagnosed as single-species
infections by microscopy, were found in 7 (25.9%) malaria patients. All sample
donors, parasitaemic and non-parasitaemic alike, had serological evidence of
parasite exposure, with 100% seropositivity to at least 54 antigens. Antigens
significantly associated with asymptomatic infections were P. falciparum MSP2,
DnaJ protein, putative E1E2 ATPase, and three others. CONCLUSION: These findings
suggest that parasite prevalence is higher than currently estimated by local
authorities based on the standard light microscopy. As transmission levels drop
in Thailand, it may be necessary to employ higher throughput and sensitivity
methods for parasite detection in the phase of malaria elimination.
PMID- 25849212
TI - Heterogeneity of equilibrium molten globule state of cytochrome c induced by weak
salt denaturants under physiological condition.
AB - While many proteins are recognized to undergo folding via intermediate(s), the
heterogeneity of equilibrium folding intermediate(s) along the folding pathway is
less understood. In our present study, FTIR spectroscopy, far- and near-UV
circular dichroism (CD), ANS and tryptophan fluorescence, near IR absorbance
spectroscopy and dynamic light scattering (DLS) were used to study the structural
and thermodynamic characteristics of the native (N), denatured (D) and
intermediate state (X) of goat cytochorme c (cyt-c) induced by weak salt
denaturants (LiBr, LiCl and LiClO4) at pH 6.0 and 25 degrees C. The LiBr-induced
denaturation of cyt-c measured by Soret absorption (Deltaepsilon400) and CD
([theta]409), is a three-step process, N <-> X <-> D. It is observed that the X
state obtained along the denaturation pathway of cyt-c possesses common
structural and thermodynamic characteristics of the molten globule (MG) state.
The MG state of cyt-c induced by LiBr is compared for its structural and
thermodynamic parameters with those found in other solvent conditions such as
LiCl, LiClO4 and acidic pH. Our observations suggest: (1) that the LiBr-induced
MG state of cyt-c retains the native Met80-Fe(III) axial bond and Trp59
propionate interactions; (2) that LiBr-induced MG state of cyt-c is more compact
retaining the hydrophobic interactions in comparison to the MG states induced by
LiCl, LiClO4 and 0.5 M NaCl at pH 2.0; and (3) that there exists heterogeneity of
equilibrium intermediates along the unfolding pathway of cyt-c as highly ordered
(X1), classical (X2) and disordered (X3), i.e., D <-> X3 <-> X2 <-> X1 <-> N.
PMID- 25849213
TI - Functional characterization of zebrafish (Danio rerio) Bcl10.
AB - The complexes formed by BCL10, MALT1 and specific members of the family of CARMA
proteins (CBM complex), have recently focused much attention because they
represent a central hub regulating activation of the transcription factor NF
kappaB following various cellular stimulations. In this manuscript, we report the
functional characterization of a Danio rerio 241 amino acids polypeptide ortholog
of the Caspase recruiting domain (CARD)-containing protein BCL10. Biochemical
studies show that zebrafish Bcl10 (zBcl10) dimerizes and binds to components of
the CBM complex. Fluorescence microscopy observations demonstrate that zBcl10
forms cytoplasmic filaments similar to that formed by human BCL10 (hBCL10).
Functionally, in human cells zBcl10 is more effective in activating NF-kappaB
compared to hBCL10, possibly due to the lack of carboxy-terminal inhibitory
serine residues present in the human protein. Also, depletion experiments carried
out through expression of short hairpin RNAs targeting hBCL10 indicate that
zBcl10 can functionally replace the human protein. Finally, we show that the
zebrafish cell line PAC2 is suitable to carry out reporter assays for monitoring
the activation state of NF- kB transcription factor. In conclusion, this work
shows that zebrafish may excellently serve as a model organism to study complex
and intricate signal transduction pathways, such as those that control NF-kappaB
activation.
PMID- 25849215
TI - Correction: P2X7 mediates ATP-driven invasiveness in prostate cancer cells.
PMID- 25849214
TI - Microparticles release by adipocytes act as "find-me" signals to promote
macrophage migration.
AB - Macrophage infiltration of adipose tissue during weight gain is a central event
leading to the metabolic complications of obesity. However, what are the
mechanisms attracting professional phagocytes to obese adipose tissue remains
poorly understood. Here, we demonstrate that adipocyte-derived microparticles
(MPs) are critical "find-me" signals for recruitment of monocytes and
macrophages. Supernatants from stressed adipocytes stimulated the attraction of
monocyte cells and primary macrophages. The activation of caspase 3 was required
for release of these signals. Adipocytes exposed to saturated fatty acids showed
marked release of MPs into the supernatant while common genetic mouse models of
obesity demonstrate high levels of circulating adipocyte-derived MPs. The release
of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase.
Further analysis identified these MPs as a central chemoattractant in vitro and
in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob
mice lead to activation of monocytes in circulation and adipose tissue of the
wild type mice. These data identify adipocyte-derived MPs as novel "find me"
signals that contributes to macrophage infiltration associated with obesity.
PMID- 25849216
TI - The evolution of WRKY transcription factors.
AB - BACKGROUND: The availability of increasing numbers of sequenced genomes has
necessitated a re-evaluation of the evolution of the WRKY transcription factor
family. Modern day plants descended from a charophyte green alga that colonized
the land between 430 and 470 million years ago. The first charophyte genome
sequence from Klebsormidium flaccidum filled a gap in the available genome
sequences in the plant kingdom between unicellular green algae that typically
have 1-3 WRKY genes and mosses that contain 30-40. WRKY genes have been
previously found in non-plant species but their occurrence has been difficult to
explain. RESULTS: Only two WRKY genes are present in the Klebsormidium flaccidum
genome and the presence of a Group IIb gene was unexpected because it had
previously been thought that Group IIb WRKY genes first appeared in mosses. We
found WRKY transcription factor genes outside of the plant lineage in some
diplomonads, social amoebae, fungi incertae sedis, and amoebozoa. This patchy
distribution suggests that lateral gene transfer is responsible. These lateral
gene transfer events appear to pre-date the formation of the WRKY groups in
flowering plants. Flowering plants contain proteins with domains typical for both
resistance (R) proteins and WRKY transcription factors. R protein-WRKY genes have
evolved numerous times in flowering plants, each type being restricted to
specific flowering plant lineages. These chimeric proteins contain not only novel
combinations of protein domains but also novel combinations and numbers of WRKY
domains. Once formed, R protein WRKY genes may combine different components of
signalling pathways that may either create new diversity in signalling or
accelerate signalling by short circuiting signalling pathways. CONCLUSIONS: We
propose that the evolution of WRKY transcription factors includes early lateral
gene transfers to non-plant organisms and the occurrence of algal WRKY genes that
have no counterparts in flowering plants. We propose two alternative hypotheses
of WRKY gene evolution: The "Group I Hypothesis" sees all WRKY genes evolving
from Group I C-terminal WRKY domains. The alternative "IIa + b Separate
Hypothesis" sees Groups IIa and IIb evolving directly from a single domain algal
gene separate from the Group I-derived lineage.
PMID- 25849218
TI - Copper-catalyzed radical methylation/C-H amination/oxidation cascade for the
synthesis of quinazolinones.
AB - A copper-catalyzed radical methylation/sp(3) C-H amination/oxidation reaction for
the facile synthesis of quinazolinone was developed. In this cascade reaction,
dicumyl peroxide acts not only as a useful oxidant but also as an efficient
methyl source. Notably, a methyl radical, generated from peroxide, was confirmed
by electron paramagnetic resonance for the first time.
PMID- 25849217
TI - Common variants at 9q22.33, 14q13.3, and ATM loci, and risk of differentiated
thyroid cancer in the French Polynesian population.
AB - BACKGROUND: French Polynesia has one of the highest incidence rates of thyroid
cancer worldwide. Relationships with the atmospheric nuclear weapons tests and
other environmental, biological, or behavioral factors have already been
reported, but genetic susceptibility has yet to be investigated. We assessed the
contribution of polymorphisms at the 9q22.33 and 14q13.3 loci identified by GWAS,
and within the DNA repair gene ATM, to the risk of differentiated thyroid cancer
(DTC) in 177 cases and 275 matched controls from the native population. PRINCIPAL
FINDINGS: For the GWAS SNP rs965513 near FOXE1, an association was found between
genotypes G/A and A/A, and risk of DTC. A multiplicative effect of allele A was
even noted. An excess risk was also observed in individuals carrying two long
alleles of the poly-alanine tract expansion in FOXE1, while no association was
observed with rs1867277 falling in the promoter region of the gene. In contrast,
the GWAS SNP rs944289 (NKX2-1) did not show any significant association. Although
the missense substitution D1853N (rs1801516) in ATM was rare in the population,
carriers of the minor allele (A) also showed an excess risk. The relationships
between these five polymorphisms and the risk of DTC were not contingent on the
body surface area, body mass index, ethnicity or dietary iodine intake. However,
an interaction was evidenced between the thyroid radiation dose and rs944289.
SIGNIFICANCE: A clear link could not be established between the high incidence in
French Polynesia and the studied polymorphisms, involved in susceptibility to DTC
in other populations. Important variation in allele frequencies was observed in
the Polynesian population as compared to the European populations. For FOXE1
rs965513, the direction of association and the effect size was similar to that
observed in other populations, whereas for ATM rs1801516, the minor allele was
associated to an increased risk in the Polynesian population and with a decreased
risk in the European population.
PMID- 25849219
TI - Bringing macromolecules into cells and evading endosomes by oxidized carbon
nanoparticles.
AB - A great challenge exists in finding safe, simple, and effective delivery
strategies to bring matters across cell membrane. Popular methods such as viral
vectors, positively charged particles and cell penetrating peptides possess some
of the following drawbacks: safety issues, lysosome trapping, limited loading
capacity, and toxicity, whereas electroporation produces severe damages on both
cargoes and cells. Here, we show that a serendipitously discovered, relatively
nontoxic, water dispersible, stable, negatively charged, oxidized carbon
nanoparticle, prepared from graphite, could deliver macromolecules into cells,
without getting trapped in a lysosome. The ability of the particles to induce
transient pores on lipid bilayer membranes of cell-sized liposomes was
demonstrated. Delivering 12-base-long pyrrolidinyl peptide nucleic acids with d
prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbone (acpcPNA)
complementary to the antisense strand of the NF-kappaB binding site in the
promoter region of the Il6 gene into the macrophage cell line, RAW 264.7, by our
particles resulted in an obvious accumulation of the acpcPNAs in the nucleus and
decreased Il6 mRNA and IL-6 protein levels upon stimulation. We anticipate this
work to be a starting point in a new drug delivery strategy, which involves the
nanoparticle that can induce a transient pore on the lipid bilayer membrane.
PMID- 25849220
TI - Meningiomas of the cerebellopontine angle: radiological differences in tumors
with internal auditory canal involvement and their influence on surgical outcome.
AB - This study explored the clinical, radiological, and pathological characteristics
of cerebellopontine angle (CPA) meningiomas with internal auditory canal (IAC)
involvement. The pre- and postoperative MR images of 193 consecutive patients
with pathologically diagnosed meningioma centered around the IAC were analyzed,
focusing on changes in the IAC, maximal axial tumor volume, peritumoral brain
edema, and postoperative residual tumor. Patient age, sex, tumor volume,
postoperative residual tumor, and pathological subtype were compared in patients
with and without IAC involvement by the tumor and among the different types of
IAC involvement. The results showed that the 71 patients (36.8%) with IAC
involvement had a higher ratio of peritumoral edema (chi(2)=5.922, P=0.015),
postoperative residual tumor (chi(2)=22.183, P< 0.001), and a predominance of the
meningothelial subtype (chi(2)=5.89, P=0 .015). Peritumoral edema was a risk
factor for IAC involvement (P=0.016, OR=2.186). Radiologically, IAC involvement
could be distinguished as intruding (31%, 22/71), filled (29.6%, 21/71), and
dilated (39.4%, 28/71). Patients with intruding IAC were significantly older
(54.5 +/- 9.54 years, P=0.021) and had the lowest postoperative residual tumor
values (42%, chi(2)=7.865, P=0.005), while those with filled IAC were more likely
to be female (95%, chi(2)=9.404, P=0.009).Our observations provide the basis for
a morphological classification of IAC involvement by CPA meningiomas and further
insight into the clinical features of these tumors.
PMID- 25849221
TI - Molecular subtyping for clinically defined breast cancer subgroups.
AB - INTRODUCTION: Breast cancer is commonly classified into intrinsic molecular
subtypes. Standard gene centering is routinely done prior to molecular subtyping,
but it can produce inaccurate classifications when the distribution of
clinicopathological characteristics in the study cohort differs from that of the
training cohort used to derive the classifier. METHODS: We propose a subgroup
specific gene-centering method to perform molecular subtyping on a study cohort
that has a skewed distribution of clinicopathological characteristics relative to
the training cohort. On such a study cohort, we center each gene on a specified
percentile, where the percentile is determined from a subgroup of the training
cohort with clinicopathological characteristics similar to the study cohort. We
demonstrate our method using the PAM50 classifier and its associated University
of North Carolina (UNC) training cohort. We considered study cohorts with skewed
clinicopathological characteristics, including subgroups composed of a single
prototypic subtype of the UNC-PAM50 training cohort (n = 139), an external
estrogen receptor (ER)-positive cohort (n = 48) and an external triple-negative
cohort (n = 77). RESULTS: Subgroup-specific gene centering improved prediction
performance with the accuracies between 77% and 100%, compared to accuracies
between 17% and 33% from standard gene centering, when applied to the prototypic
tumor subsets of the PAM50 training cohort. It reduced classification error rates
on the ER-positive (11% versus 28%; P = 0.0389), the ER-negative (5% versus 41%;
P < 0.0001) and the triple-negative (11% versus 56%; P = 0.1336) subgroups of the
PAM50 training cohort. In addition, it produced higher accuracy for subtyping
study cohorts composed of varying proportions of ER-positive versus ER-negative
cases. Finally, it increased the percentage of assigned luminal subtypes on the
external ER-positive cohort and basal-like subtype on the external triple
negative cohort. CONCLUSIONS: Gene centering is often necessary to accurately
apply a molecular subtype classifier. Compared with standard gene centering, our
proposed subgroup-specific gene centering produced more accurate molecular
subtype assignments in a study cohort with skewed clinicopathological
characteristics relative to the training cohort.
PMID- 25849222
TI - The effect of desflurane on neuronal communication at a central synapse.
AB - Although general anesthetics are thought to modify critical neuronal functions,
their impact on neuronal communication has been poorly examined. We have
investigated the effect induced by desflurane, a clinically used general
anesthetic, on information transfer at the synapse between mossy fibers and
granule cells of cerebellum, where this analysis can be carried out extensively.
Mutual information values were assessed by measuring the variability of
postsynaptic output in relationship to the variability of a given set of
presynaptic inputs. Desflurane synchronized granule cell firing and reduced
mutual information in response to physiologically relevant mossy fibers patterns.
The decrease in spike variability was due to an increased postsynaptic membrane
excitability, which made granule cells more prone to elicit action potentials,
and to a strengthened synaptic inhibition, which markedly hampered membrane
depolarization. These concomitant actions on granule cells firing indicate that
desflurane re-shapes the transfer of information between neurons by providing a
less informative neurotransmission rather than completely silencing neuronal
activity.
PMID- 25849223
TI - Once-daily fluticasone furoate/vilanterol 100/25 mcg versus twice daily
combination therapies in COPD - mixed treatment comparisons of clinical efficacy.
AB - BACKGROUND: Fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg is a once-daily
inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) treatment approved
in the United States, Canada and Europe for the long-term maintenance therapy of
COPD. We report data from mixed treatment comparisons (MTC) of once-daily FF/VI
against established twice-daily ICS/LABA combination therapies on clinical
efficacy outcomes. METHODS: Data from 33 parallel-group randomised controlled
trials (RCTs) of ICS/LABAs, of >=8 weeks' duration in patients >=12 years of age
with COPD, identified by systematic review, were analysed using covariate
adjusted Bayesian hierarchical models for three efficacy outcomes. Lung function,
assessed by change from baseline in forced expiratory volume in one second
(FEV1), was the outcome of primary interest (n = 28 studies). Secondary
objectives were assessment of annual rate of moderate/severe exacerbations (n =
15) and patient-reported health status, measured by change from baseline in St
George's Respiratory Questionnaire (SGRQ) Total score (n = 20). Overall, 25
different treatments were included in the MTC; we report findings, including
probabilities of non-inferiority, for comparisons of once-daily FF/VI 100/25 mcg
with twice-daily fluticasone propionate (FP)/salmeterol (SAL) 500/50 mcg and
budesonide (BUD)/formoterol (FORM) 400/12 mcg. RESULTS: For FEV1, FF/VI 100/25
mcg demonstrated >99% probability of non-inferiority to FP/SAL 500/50 mcg and
BUD/FORM 400/12 mcg using a 50 mL margin. For annual rate of moderate/severe
exacerbations, FF/VI 100/25 mcg demonstrated 73% and 77% probability of non
inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg, respectively, using a
10% rate ratio margin. For SGRQ Total score, the corresponding probabilities of
non-inferiority were 99% and 98%, respectively, on a 2-unit margin. Significant
covariate effects were identified: increased age was associated with
deterioration in FEV1 and reduced exacerbation frequency; shorter study duration
was associated with reduced exacerbation frequency. CONCLUSIONS: FF/VI 100/25 mcg
was comparable with corresponding doses of FP/SAL and BUD/FORM on lung function
and health status outcomes. Non-inferiority on moderate/severe exacerbation rate
was not demonstrated to the same degree of confidence, though observed rates were
similar. Model limitations include a weak treatment network for the exacerbation
analysis and variability across the included studies. Our data support previous
RCT findings suggesting that the efficacy of FF/VI 100/25 mcg on lung function
and health status in COPD is comparable with twice-daily ICS/LABAs.
PMID- 25849224
TI - Adherence to Oral Medications for Hypertension and Diabetes in Veterans with
Comorbid Airflow Limitation.
AB - RATIONALE: Diabetes and hypertension are common among patients with airflow
limitation and contribute to cardiovascular (CV) mortality, one of the leading
causes of death among patients with airflow limitation. OBJECTIVES: Our goal was
to examine the association of severity of airflow limitation with adherence to
medications for hypertension and diabetes. METHODS: We identified 7,359 veterans
with hypertension and/or diabetes in the Veterans Integrated Service Network-20.
Entry date into the cohort was defined as the date of a patient's first pulmonary
function testing (PFT). Diagnostic codes (ICD-9), PFT, and pharmacy data were
available via the electronic medical record or via direct interrogation of PFT
equipment. Our primary exposure was airflow limitation defined as FEV1 >= 80%
predicted (normal), 80 > FEV1 >= 50% predicted (mild/moderate), 50 > FEV1 >= 30%
predicted (severe), and FEV1 < 30% predicted (very severe). We assessed adherence
using a validated method based on electronic pharmacy refill data and defined
adherence as >= 80% medication possession for the period 6-12 months after
enrollment. Medications of interest included beta-blockers, calcium channel
blockers, thiazides, and angiotensin-converting-enzyme inhibitors for patients
with hypertension, and metformin and sulfonylureas for patients with diabetes. We
used logistic regression models to assess the association between severity of
airflow limitation and adherence, adjusted for demographics, health behaviors,
and comorbidities. MEASUREMENTS AND MAIN RESULTS: Overall adherence was poor
(44.6-55.1%). Among patients with hypertension, when compared with subjects with
normal FEV1, subjects with each category lower of FEV1 were less adherent to beta
blockers, with an odds ratio (OR) of 0.87 (95% confidence interval [CI], 0.80
0.95); calcium channel blockers, with an OR of 0.83 (95% CI, 0.74-0.93); and
angiotensin-converting-enzyme inhibitors with an OR of 0.91 (95% CI, 0.84-0.99).
Airflow limitation was not associated with adherence to thiazides. Among patients
with diabetes, we found no significant association of FEV1 with adherence,
although a similar lower trend with increasing airflow limitation. In a
sensitivity analysis limited to patients with chronic obstructive pulmonary
disease, we found a nonstatistically significant trend for decreased adherence to
beta-blockers, calcium channel blockers, and angiotensin-converting-enzyme
inhibitors in subjects with higher GOLD (Global Initiative for Chronic
Obstructive Lung Disease) stage. CONCLUSIONS: Severity of airflow limitation is
associated with decreased adherence to beta-blockers, calcium channel blockers,
and angiotensin-converting-enzyme inhibitors. The decreased adherence to these
medications may be related to adverse effects on symptoms in patients with lung
disease, and may partially explain excess CV mortality in these patients.
PMID- 25849225
TI - Genetic depletion and pharmacological targeting of alphav integrin in breast
cancer cells impairs metastasis in zebrafish and mouse xenograft models.
AB - INTRODUCTION: Increased expression of alphav integrins is frequently associated
with tumor cell adhesion, migration, invasion and metastasis, and correlates with
poor prognosis in breast cancer. However, the mechanism by which alphav integrins
can enhance breast cancer progression is still largely unclear. The effects of
therapeutic targeting of alphav integrins in breast cancer also have yet to be
investigated. METHODS: We knocked down alphav integrin in MDA-MB-231 and MCF10A
M4 breast cancer cells, or treated these cells with the alphav antagonist
GLPG0187. The effects of alphav integrin depletion on mesenchymal markers,
transforming growth factor-beta (TGF-beta)/Smad signaling and TGF-beta-induced
target gene expression were analyzed in MDA-MB-231 cells by RNA analysis or
Western blotting. The function of alphav integrin on breast cancer cell migration
was investigated by transwell assay in vitro, and its effect on breast cancer
progression was assessed by both zebrafish and mouse xenografts in vivo. In the
mouse model, GLPG0187 was administered separately, or in combination with the
standard-of-care anti-resorptive agent zoledronate and the chemotherapeutic drug
paclitaxel, to study the effects of combinational treatments on breast cancer
metastasis. RESULTS: Genetic interference and pharmacological targeting of alphav
integrin with GLPG0187 in different breast cancer cell lines inhibited invasion
and metastasis in the zebrafish or mouse xenograft model. Depletion of alphav
integrin in MDA-MB-231 cells inhibited the expression of mesenchymal markers and
the TGF-beta/Smad response. TGF-beta induced alphav integrin mRNA expression and
alphav integrin was required for TGF-beta-induced breast cancer cell migration.
Moreover, treatment of MDA-MB-231 cells with non-peptide RGD antagonist GLPG0187
decreased TGF-beta signaling. In the mouse xenografts GLPG0187 inhibited the
progression of bone metastasis. Maximum efficacy of inhibition of bone metastasis
was achieved when GLPG0187 was combined with the standard-of-care metastatic
breast cancer treatments. CONCLUSION: These findings show that alphav integrin is
required for efficient TGF-beta/Smad signaling and TGF-beta-induced breast cancer
cell migration, and for maintaining a mesenchymal phenotype of the breast cancer
cells. Our results also provide evidence that targeting alphav integrin could be
an effective therapeutic approach for treatment of breast cancer tumors and/or
metastases that overexpress alphav integrin.
PMID- 25849227
TI - EPR spin trapping evidence of radical intermediates in the photo-reduction of
bicarbonate/CO2 in TiO2 aqueous suspensions.
AB - Using the EPR spin trapping technique, we prove that simultaneous reactions take
place in illuminated suspensions of TiO2 in aqueous carbonate solutions (pH ~ 7).
The adsorbed HCO3(-) is reduced to formate as directly made evident by the
detection of formate radicals (CO2(-)). In addition, the amount of OH radicals
from the photo-oxidation of water shows a linear dependence on the concentration
of bicarbonate, indicating that electron scavenging by HCO3(-) increases the
lifetime of holes. In a weakly alkaline medium, photo-oxidation of HCO3(-)/CO3(2
) to CO3(-) interferes with the oxidation of water. A comparative analysis of
different TiO2 samples shows that formation of CO2(-) is influenced by factors
related to the nature of the surface, once expected surface area effects are
accounted for. Modification of the TiO2 surface with noble metal nanoparticles
does not have unequivocal benefits: the overall activity improves with Pd and Rh
but not with Ru, which favours HCO3(-) photo-oxidation even at pH = 7. In
general, identification of radical intermediates of oxidation and reduction
reactions can provide useful mechanistic information that may be used in the
development of photocatalytic systems for the reduction of CO2 also stored in the
form of carbonates.
PMID- 25849226
TI - Mesenchymal chondrosarcoma of bone and soft tissue: a systematic review of 107
patients in the past 20 years.
AB - BACKGROUND: Mesenchymal chondrosarcoma(MCS) is a rare high-grade variant of
chondrosarcoma. Consensus has not been reached on its optimal management.
Resection with wide margins is usually recommended, but the effect of margins has
been demonstrated by little positive evidence. Moreover, the effectiveness of
adjuvant chemo- and/or radiotherapy remains controversial. OBJECTIVES: To
describe the clinical characteristics and outcomes of MCS of bone and soft
tissue, to assess the efficacies of surgery, chemotherapy and radiation, and
finally to deliver a more appropriate therapy. MATERIALS AND METHODS: We reviewed
EMBASE-, MEDLINE-, Cochrane-, Ovid- and PubMed-based to find out all cases of MCS
of bone and soft tissue described between April 1994 and April 2014. Description
of treatment and regular follow-up was required for each study. Language was
restricted to English and Chinese. Issues of age, gender, location, metastasis,
and treatment were all evaluated for each case. Kaplan-Meier Method and Cox
Proportional Hazard Regression Model were used in the survival analysis. RESULTS:
From the 630 identified publications, 18 meeting the inclusion criteria were
selected, involving a total of 107 patients. Based on these data, the 5-, 10-and
20-year overall survival are 55.0%, 43.5% and 15.7% respectively. The 5-, 10-, 20
year event-free survival rates are 45.0%, 27.2% and 8.1%, respectively.
Treatment without surgery is associated with poorer overall survival and event
free survival. Negative surgical margins could significantly bring down the local
recurrence rate and are associated with a higher event-free survival rate.
Chemotherapy regime based on anthracyclines does not benefit the overall
survival. The addition of radiation therapy is not significantly associated with
the overall or event-free survival. However, we recommend radiation as the
salvage therapy for patients with positive margin so as to achieve better local
control. CONCLUSIONS: This review shows that surgery is essential in the
management of MCS of bone and soft tissue. Appropriate adjuvant therapy may
reduce local recurrence, but cannot benefit the overall survival.
PMID- 25849228
TI - Viral shedding and susceptibility to oseltamivir in hospitalized
immunocompromised patients with influenza in the Influenza Resistance Information
Study (IRIS).
AB - BACKGROUND: Immunocompromised patients are at greater risk of complicated
influenza and may be more likely to develop antiviral resistance. This
observational substudy of the Influenza Resistance Information Study
(NCT00884117) aimed to study antiviral resistance in immunocompromised patients
with influenza and characterize its effect on clinical and virological outcomes.
METHODS: Eligible immunocompromised patients were aged >=1 year with a local
rapid diagnostic or PCR test positive for influenza <=96 h after diagnosis and
with influenza symptoms. Nasal and throat swabs were taken for RT-PCR analysis on
day 1 and then every 3 days until patients were virus-free. Resistance was
assessed by mutation-specific RT-PCR, phenotypic susceptibility analysis and
Sanger sequencing. RESULTS: Of 42 patients enrolled, 29 (69%) were influenza
positive (RT-PCR) on day 1: 18 adults and 11 children aged 1-12 years. Six
patients were severely immunocompromised. On days 3, 6 and 9, most patients
tested (18/24, 9/15 and 6/9, respectively) had not cleared the virus. Two of five
patients assessed after day 9 continued shedding virus until day 15. H1N1pdm09
viruses harbouring H275Y mutations were detected in post-baseline samples from
four patients (aged 52-61 years), one of whom had prolonged viral shedding. No
genotypic antiviral resistance was detected in the other 20 treated patients
(prevalence of resistance, 17%). Correlation between level of immune compromise
and resistance or outcomes could not be assessed. Ten patients (seven influenza
positive) were admitted to intensive care and three died. CONCLUSIONS: In these
patients with mild/moderate immunocompromise, emergence of oseltamivir-resistant
viruses was not common. Severity of influenza symptoms ranged from mild to
moderate, but correlation with level of compromise could not be determined.
PMID- 25849229
TI - Sickness absence: a concern for all of us.
PMID- 25849230
TI - Should blood glucose strips be used in type 2 diabetes?
PMID- 25849231
TI - Undernutrition in older people in Australia.
AB - Despite being preventable and treatable, undernutrition remains a problem for
many older people in tertiary healthcare settings. Nurses have a crucial role in
assisting people who are unable to eat independently and are uniquely positioned
to implement solutions that will lead to better nutritional care. However, what
is known about the management of undernutrition is not informing nursing
practice. This study used action research, underpinned by the 'participatory
world view', to address the theory-practice gap. Data and between-method
triangulation were used to collect and analyse qualitative non-participant
observations and action research group data. Set Up Ready For Dining (SURFD) was
developed and implemented by nurses to improve patient mealtimes. Findings show
that nursing practice in nutritional care is influenced by technique within the
healthcare context that emphasises operational efficiency, and by the choices
that nurses made around being the patient advocate during mealtimes.
PMID- 25849232
TI - The efficacy of feeding tubes: confirmation and loss.
AB - Around 5% of hospital patients require enteral tube feeding, yet its efficacy and
costs are poorly understood. The authors examined radio-opacity, reason for
repeat X-ray and overall cost in consecutive patients having tubes confirmed by X
ray when using polyvinylchloride (PVC) Ryles tubes versus CORFLO(r) (CORTRAK
Medsystems) polyurethane tubes (PUTs); and confirmation method and reason for
tube loss over an enteral episode. Despite higher PUT cost, because more Ryles
tubes required re-X-ray +/- radio-contrast injection (0% compared with 26%,
p=0.029), overall cost was almost identical (Corflo: L54.2 vs Ryles: L54.6).
Confirmation of tube position by X-ray remains more common than pH (51% compared
with 45%) and tube loss is mostly as a result of inadvertent patient removal
(54%). These studies show that: a) when using X-ray confirmation, PUTs and PVC
Ryles tube cost is similar; b) despite pH being taught as first-line
confirmation, X-ray remains the most common method therefore PUT use may further
reduce cost when staff and outcome costs are included. In addition, more reliable
and repeatable bedside confirmation methods are required; c) most tube loss is
potentially preventable by use of nasal bridles. Larger studies are required to
establish baseline data on problems and cost-effectiveness of enteral tube
feeding before intervention trials.
PMID- 25849233
TI - Contracting for enteral tube feeding.
PMID- 25849234
TI - A CBT-based anxiety management workshop in first-episode psychosis.
AB - When co-occurring with psychosis, anxiety can adversely affect social and
occupational functioning and can cause debilitating levels of distress. This
article describes a single-centre three-phase service development project
culminating in the introduction of 1-day anxiety management workshops for service
users of an Early Intervention for Psychosis Service (EIPS). The workshops, which
were run by a mental health nurse and an assistant psychologist, attracted 12
participants with a first episode of psychosis and co-morbid anxiety.
Quantitative and qualitative measures demonstrated a statistically significant
reduction (p<0.0005) in subjective anxiety levels following the intervention, and
that participants felt they were likely to make use of the skills in the future.
It can be concluded that such workshops are not only time-and cost-effective, but
also valuable in delivering brief interventions based on cognitive behavioural
therapy (CBT) to service users with a first episode of psychosis.
PMID- 25849235
TI - Disclosing a dyslexic identity.
AB - Potential difficulties experienced by nursing students diagnosed with dyslexia
can be minimised with the introduction of appropriate policies and guidance
around reasonable adjustment and support. In order to access all relevant
services, however, a student must actively decide to disclose their dyslexic
identity to relevant faculty personnel. Disclosure of such personal information
is a complex matter and, critically, requires a receptive environment where
diversity and disability are embraced in a positive and meaningful way. The act
of disclosure for the most part has previously been described in simplistic
terms, with the focus being solely on the behaviour itself and not on the
individual's own positioning of their dyslexia or the social context associated
with the act. There is an onus on all students with dyslexia to self-monitor how
this aspect of their identity interacts with their professional duty of care.
PMID- 25849236
TI - Have OSCEs come of age in nursing education?
AB - This article is intended to contribute to the current debate as to whether the
objective structured clinical examination (OSCE) should become a standard
assessment tool for undergraduate nursing education as they currently are for
medicine. The authors describe how one UK university developed an OSCE for a
nursing undergraduate programme with the aim of emphasising the need for nursing
students to be competent in clinical skills and offering a means of standardising
the assessment of these skills. There has been an increasing number of research
studies carried out in this area at international level and this article's main
contribution to the literature is the description of the Angoff standard-setting
procedure that was used to calibrate the OSCE at this University and which makes
it the first nursing OSCE in the UK to incorporate a scientific standard-setting
procedure.
PMID- 25849237
TI - Examining the effect of patient-centred care on outcomes.
AB - Within patient-centered care (PCC), the individual is viewed as an active member
of the healthcare team. While there has been recent interest in conducting
systematic reviews to examine the effectiveness of PCC interventions, various
studies fall short in explaining the type of intervention most effective in
producing significant changes to desired outcomes. The purpose of this systematic
review was to determine the characteristics of PCC interventions that have
demonstrated effectiveness in enhancing the quality of care and performance of
self-care behaviours. A systematic review of 40 studies that addressed PCC
interventions, included samples over the age of 18 years, and were published
between 1995 and 2014 was performed. Descriptive statistics were used to
delineate study, participant, and intervention characteristics. Results suggest
PCC-based interventions are not effective when delivered to individuals living
with chronic illnesses.
PMID- 25849238
TI - Binge drinking and cognitive impairment in young people.
AB - AIMS AND OBJECTIVES: To investigate the links between the binge pattern of
drinking and the development of cognitive impairment in young adults in the UK.
To determine from the findings whether cognitive impairment is an additional
public health concern manifesting from this form of alcohol misuse and its
relevance to nursing practice. BACKGROUND: Young adults in the UK are
participating in binge drinking; a 'harmful' form of alcohol misuse. Morbidity
and mortality associated with alcohol misuse is already a public health concern.
DESIGN: Literature review. METHOD: Multiple database searches were undertaken,
which revealed three case-control studies. The studies all investigated the binge
pattern of drinking as well as meeting the following inclusion criteria; primary
research published from 2005 onwards, used a human sample, participants were aged
18 to 24 and cognitive function was tested. RESULTS: The quantitative data found
cognitive impairment present in young adult binge drinkers, specifically in
regions of the frontal lobe, temporal lobe and hippocampus. Individually the
studies did not pose strong enough evidence to generalise findings. However,
collectively the core findings along with previous studies can validate the link
between binge drinking and cognitive impairment. CONCLUSION: Nurse-led alcohol
misuse screening and brief intervention is the most effective public health
prevention strategy. It is important for nurses to keep abreast of current
evidence to better inform their practice and the information they provide to
their service users. This review emphasises the need for nurses to routinely
screen young adults and address the associated risk to cognitive function when
participating in harmful drinking.
PMID- 25849239
TI - Duty to warn of risks moves to a prudent patient approach.
AB - The United Kingdom Supreme Court has ruled that nurses, and other health
professionals, can no longer paternalistically decide what information about the
risks inherent in treatment should be disclosed to patients when obtaining
consent ( Montgomery v Lanarkshire Health Board [2015] ). Patients must instead
be given sufficient information about material risks to enable them to make an
informed decision about whether to accept or refuse treatment. This article
considers the impact of the Supreme Court ruling on nursing practice.
PMID- 25849240
TI - Relationships: from staff nurse to nurse consultant: Part 3: teamwork.
PMID- 25849241
TI - Reliance on technology and the future of dialysis.
AB - Emma Blakey discusses her experience of working on a dialysis unit, how strange
it felt to be so reliant on machines and how important it is to be aware of
national policy debates.
PMID- 25849242
TI - The future education of nurses and healthcare assistants.
PMID- 25849243
TI - Applying the lessons of the Francis Inquiries: Culture Change, part two.
AB - In this second part of his two-part column John Tingle continues his discussion
of the Department of Health's progress report on applying the lessons learned
from the tragic events at Mid Staffordshire NHS Foundation Trust.
PMID- 25849244
TI - Building resilience in ward leaders with Restorative Supervision.
PMID- 25849246
TI - Regulation of transcriptionally active genes via the catalytically inactive Cas9
in C. elegans and D. rerio.
PMID- 25849245
TI - Association between variants in the interferon lambda 4 locus and substitutions
in the hepatitis C virus non-structural protein 5A.
AB - BACKGROUND & AIMS: Single nucleotide polymorphisms within the interferon lambda 4
(IFNL4) locus are strongly associated with spontaneous clearance of hepatitis C
virus (HCV) infection and early viral response to interferon therapy. Interaction
between host genotype and amino acid substitutions might also influence the risk
of antiviral resistance in interferon-free direct acting antiviral (DAA)
therapies. METHODS: The relationship between IFNL4 genotype and HCV substitutions
was analyzed in 929 patients with chronic HCV genotype 1b infection. Ultra-deep
sequencing and quasispecies reconstruction was performed on the N-terminal region
of NS5A in 57 patients. RESULTS: IFNL4 genotype was strongly associated with HCV
NS5A Y93 and core protein substitutions, and the number and diversity of
predicted quasispecies was marginally greater in IFNL4 TT/TT patients compared to
TT/DeltaG, DeltaG/DeltaG patients. RNA secondary structure prediction of the NS5A
region suggests that variable sites are more likely to occupy unpaired, high
entropy positions. CONCLUSIONS: HCV infection is proposed to induce a more
efficient antiviral response in individuals with the IFNL4 TT/TT genotype that
results either in viral clearance or selection for viral adaptations. The
association between IFNL4 TT/TT genotype and Y93 substitutions may impact the
risk of antiviral resistance in NS5A inhibitors in DAA therapy.
PMID- 25849247
TI - Shed NKG2D ligand boosts NK cell immunity.
AB - Ligands for natural killer (NK) cell activating receptors can be released from
tumor cells and are believed to promote tumor growth by acting as decoys for
effector lymphocytes. In a recent paper published in Science, Deng et al. report
another scenario in which a shed form of the MULT1 mouse NKG2D ligand boosts NK
cell functions.
PMID- 25849248
TI - Intron targeting-mediated and endogenous gene integrity-maintaining knockin in
zebrafish using the CRISPR/Cas9 system.
PMID- 25849249
TI - CD146: the unveiling of a pro-angiogenic netrin receptor.
AB - Netrin-1, a classic neuronal guidance cue, can promote angiogenesis under certain
developmental and pathological conditions, but key receptors on vascular
endothelium have remained elusive. A recent study published in Cell Research by
Tu et al. reveals that CD146, an endothelial receptor of the immunoglobulin
superfamily, binds netrin-1 with high affinity and may play an important role in
regulating angiogenesis.
PMID- 25849250
TI - Protein composition of the outermost exosporium-like layer of Clostridium
difficile 630 spores.
AB - Clostridium difficile spores are considered the morphotype of infection,
transmission and persistence of C. difficile infections. There is a lack of
information on the composition of the outermost exosporium layer of C. difficile
spores. Using recently developed exosporium removal methods combined with MS/MS,
we have established a gel-free approach to analyze the proteome of the exosporium
of C. difficile spores of strain 630. A total of 184 proteins were found in the
exosporium layer of C. difficile spores. We identified 7 characterized spore coat
and/or exosporium proteins; 6 proteins likely to be involved in spore resistance;
6 proteins possibly involved in pathogenicity; 13 uncharacterized proteins; and
146 cytosolic proteins that might have been encased into the exosporium during
assembly, similarly as reported for Bacillus anthracis and Bacillus cereus
spores. We demonstrate through Flag-fusions that CotA and CotB are mainly located
in the spore coat, while the exosporium collagen-like glycoproteins (i.e. BclA1,
BclA2 and BclA3), the exosporium morphogenetic proteins CdeC and CdeM, and the
uncharacterized exosporium proteins CdeA and CdeB are mainly located in the
exosporium layer of C. difficile 630 spores. This study offers novel candidates
of C. difficile exosporium proteins as suitable targets for detection, removal
and spore-based therapies. BIOLOGICAL SIGNIFICANCE: This study offers a novel
strategy to identify proteins of the exosporium layer of C. difficile spores and
complements previous proteomic studies on the entire C. difficile spores and
spore coat since it defines the proteome of the outermost layer of C. difficile
spores, the exosporium. This study suggests that C. difficile spores have several
proteins involved in protection against environmental stress as well as putative
virulence factors that might play a role during infection. Spore exosporium
structural proteins were also identified providing the ground basis for further
functional studies of these proteins. Overall this work provides new protein
target for the diagnosis and/or therapeutics that may contribute to combat C.
difficile infections.
PMID- 25849251
TI - Transcriptomic and proteomic analyses of splenic immune mechanisms of rainbow
trout (Oncorhynchus mykiss) infected by Aeromonas salmonicida subsp. salmonicida.
AB - Furunculosis caused by Aeromonas salmonicida subsp. salmonicida is an epidemic
disease among salmonids, including rainbow trout (Oncorhynchus mykiss). However,
the immune mechanisms that are elicited in rainbow trout against the invasion of
A. salmonicida are not yet fully understood. In this study, we examined the
spleen to investigate the immune response of rainbow trout at 3days post
infection by A. salmonicida at the transcriptome and proteome levels by using
Illumina-seq and iTRAQ methods, respectively. A total of 1036 genes and 133
proteins were found to undergo differential expression during the immune response
of the spleen against A. salmonicida infection. Gene ontology and KEGG analysis
were conducted among the differentially expressed genes and proteins, revealing
that immune system process and response to stimulus were the top two biological
processes, and immune system, signaling molecules and interaction, and immune
diseases were the differential pathways activated. Correlation analysis of
transcriptomic and proteomic results showed 17 proteins (11 upregulated and 6
downregulated) having consistent expression at RNA and protein levels. Moreover,
protein-protein interaction analysis showed that diseases, proteasome, aminoacyl
tRNA biosynthesis, and nucleotide metabolism were the main interactions among the
consistently expressed proteins. Consequently, these upregulated proteins,
namely, ferritin, CD209, IL13Ralpha1, VDAC2, GIMAP7, PSMA1, and two ANXA11s could
be considered as potential biomarkers for rainbow trout immune responses.
BIOLOGICAL SIGNIFICANCE: This study provides the first identification of immune
markers through an analysis of the differential expression of both genes and
their corresponding protein products in the spleen of rainbow trout after
infection by A. salmonicida, shedding light on the molecular mechanisms triggered
in rainbow trout against A. salmonicida infection and providing new molecular
targets for further immunological research in fish.
PMID- 25849252
TI - A comparative proteome analysis reveals flagellin, chemotaxis regulated proteins
and amylovoran to be involved in virulence differences between Erwinia amylovora
strains.
AB - Erwinia amylovora is a Gram-negative bacterium that causes the destructive
disease fire blight affecting most members of the Rosaceae family, of which apple
and pear are economically the most important hosts. E. amylovora has been
considered as a homogeneous species in whole, although significant differences in
virulence patterns have been observed. However, the underlying causes of the
differences in virulence remain to be discovered. In a first-time comparative
proteomic approach using E. amylovora, 2D differential in-gel electrophoresis
(DIGE) was used to identify proteins that could explain the gradual difference in
virulence between four different strains. Two important proteins were identified,
FliC and CheY, both involved in flagella structure, motility and chemotaxis,
which were more abundant in the least virulent strain. In the highly virulent
strains the protein GalF, involved in amylovoran production, was more abundant,
which was consistent with the higher expression of the gene and the higher
amylovoran content in this strain in vitro. Together, these results confirm the
involvement of amylovoran in virulence, but also imply an indirect role of
flagellin in virulence as elicitor of plant defence. BIOLOGICAL SIGNIFICANCE:
This research provides new insights into our current understanding of the
virulence of Erwinia amylovora. This plant-pathogen is considered a homogeneous
species although different strains show differences in virulence. Despite the
efforts made on the genomic level which resulted in the discovery of virulence
factors, the reason for the different virulence patterns between strains has not
yet been identified. In our lab we used a comparative proteomic approach, which
has never been published before, to identify proteins involved in these
differences between strains and hereby possibly involved in virulence. Our
results provide interesting insights in virulence and present us with the
opportunity to glance into the proteome of E. amylovora.
PMID- 25849253
TI - Production of cellobionate from cellulose using an engineered Neurospora crassa
strain with laccase and redox mediator addition.
AB - We report a novel production process for cellobionic acid from cellulose using an
engineered fungal strain with the exogenous addition of laccase and a redox
mediator. A previously engineered strain of Neurospora crassa (F5?ace-1?cre
1?ndvB) was shown to produce cellobionate directly from cellulose without the
addition of exogenous cellulases. Specifically, N. crassa produces cellulases,
which hydrolyze cellulose to cellobiose, and cellobiose dehydrogenase (CDH),
which oxidizes cellobiose to cellobionate. However, the conversion of cellobiose
to cellobionate is limited by the slow re-oxidation of CDH by molecular oxygen.
By adding low concentrations of laccase and a redox mediator to the fermentation,
CDH can be efficiently oxidized by the redox mediator, with in-situ re-oxidation
of the redox mediator by laccase. The conversion of cellulose to cellobionate was
optimized by evaluating pH, buffer, and laccase and redox mediator addition time
on the yield of cellobionate. Mass and material balances were performed, and the
use of the native N. crassa laccase in such a conversion system was evaluated
against the exogenous Pleurotus ostreatus laccase. This paper describes a working
concept of cellobionate production from cellulose using the CDH-ATBS-laccase
system in a fermentation system.
PMID- 25849254
TI - GRECCAR 8: impact on survival of the primary tumor resection in rectal cancer
with unresectable synchronous metastasis: a randomized multicentre study.
AB - BACKGROUND: A majority of patients with rectal cancer and metastasis are not
eligible to curative treatment because of an extensive and unresectable
metastatic disease. Primary tumor resection is still debated in this situation.
Rectal surgery treats or prevents the symptoms and avoids the risk of acute
complications related to the primary tumor. Several studies on colorectal cancers
seem to show interesting results in terms of survival in favor to the resection
of the primary tumor. To date, no randomized trial or even a prospective study
has assessed the impact of primary tumor resection on overall survival in
patients with colorectal cancer with unresectable metastasis. All published
studies were retrospective and included colon and rectal cancers. Rectal cancer
is associated with specific problems related to the rectal surgery. Surgery is
more complex, and may be source of more morbidity and postoperative functional
dysfunctions (stoma, digestive, sexual, urinary) than colic surgery. On the other
hand, symptoms related to the progression of rectal tumor are often very
disabling: pain, rectal syndrome. METHODS/DESIGN: GRECCAR 8 is a multicentre
randomized open-label controlled trial aimed to evaluate the impact on survival
of the primary tumor resection in rectal cancer with unresectable synchronous
metastasis. Patients must undergo upfront systemic chemotherapy for at least 4
courses before inclusion. Patients with progressive metastatic disease during
upfront chemotherapy will be excluded from the study. Patients will be randomly
assigned in a 1:1 ratio to Arm A: primary tumor resection followed by systemic
chemotherapy versus Arm B: systemic chemotherapy alone. Primary endpoint will be
overall survival measured from the date of randomization to the date of death or
to the end of follow-up (2 years). Secondary endpoints will include progression
free survival, quality of life, toxicity of chemotherapy, response of the primary
tumor and metastatic disease to chemotherapy, postoperative morbidity and
mortality, rate of patient not eligible for postoperative chemotherapy (arm A),
primary tumor related complications and rate of emergency surgery (arm B). The
number of patients needed is 290. TRIAL REGISTRATION: ClinicalTrial.gov:
NCT02314182.
PMID- 25849255
TI - N-Terminal Modification with Pseudo-Bifunctional PEG-Hexadecane Markedly Improves
the Pharmacological Profile of Human Growth Hormone.
AB - Human growth hormone (hGH) has been used to treat children with short stature,
renal failure, and Turner's syndrome. However, clinical application of hGH
suffers from its short plasma half-life and low bioavailability. PEGylation and
albumin binding are two of the most effective approaches to prolong the plasma
half-life of hGH. However, the steric shielding effects of polyethylene glycol
(PEG) and albumin can drastically decrease the bioactivity of hGH, which is
opposite to the increased pharmacokinetics (PK). In the present study, a long
acting hGH with markedly improved pharmacological profile was rationally designed
and prepared by N-terminal modification of hGH with pseudo-bifunctional PEG
hexadecane by using PEG (3.5 kDa or 10 kDa) as the linker. PEGylation and albumin
binding with hexadecane can increase the hydrodynamic volume and decrease the
immunogenicity of hGH, which thereby markedly increases the PK of hGH. Since N
terminus is far from the bioactive domain of hGH, N-terminal modification of hGH
can minimize the steric shielding effects on the bioactive domain of hGH.
Hexadecane-bound albumin can be slowly released from hGH during the in vivo
circulation, which can slowly restore the bioactivity of hGH. Thus, the high
bioactivity of PEG-hexadecane modified hGH (hGH-PEG-HD) was synergistically
achieved by N-terminal modification with pseudo-bifunctional PEG-hexadecane and
slow-release of albumin. The high pharmacodynamics (PD) of hGH-PEG-HD was due to
the synergistic effect of the high bioactivity and the overall increased PK.
PMID- 25849256
TI - Fullerene up-take alters bilayer structure and elasticity: A small angle X-ray
study.
AB - The coupling of fullerene (C60) to the structure and elasticity of 1-palmitoyl-2
oleoyl-sn-glycero-3-phosphocholine bilayers has been explored by synchrotron
small angle X-ray scattering. Multilamellar vesicles were loaded with 0, 2 and 10
mol.% of C60 and studied in a temperature range from 15 to 65 degrees C. The
addition of C60 caused an increase in the bilayer undulations (~ 20%), in the
bilayer separation (~ 15%), in the linear expansion coefficient and caused a drop
in the bending rigidity of the bilayers (20-40%). Possible damaging effects of
fullerene on biomembranes are mainly discussed on the basis of altered bilayer
fluidity and elasticity changes.
PMID- 25849258
TI - Structural control of nonadiabatic bond formation: the photochemical formation
and stability of substituted 4a,4b-dihydrotriphenylenes.
AB - Nonadiabatic photocyclization makes bonds and is the first step in the
photoinduced cyclodehydrogenation of ortho-arenes to yield polycyclic aromatic
hydrocarbons. How molecular structure alters potential-energy landscapes, excited
state dynamics, and stabilities of reactants and intermediates underlies the
feasibility of desirable photochemistry. In order to gain insight into these
structure-dynamics relationships, we have used femtosecond transient absorption
spectroscopy (TAS) to examine photoinduced dynamics of 1,2,3-triphenylbenzene
(TPB) and ortho-quaterphenyl (OQTP), phenyl-subsituted analogues of ortho
terphenyl (OTP). Dynamics of TPB and OTP are quite similar: TPB exhibits fast
(7.4 ps) excited-state decay with concomitant formation and vibrational
relaxation of 9-phenyl-dihydrotriphenylene (9-phenyl DHT). In contrast,
photoexcited OQTP exhibits multistate kinetics leading to formation of 1-phenyl
DHT. Excited-state calculations reveal the existence of two distinct minima on
the OQTP S1 surface and, together with photophysical data, support a mechanism
involving both direct cyclization by way of an asymmetric structure and indirect
cyclization by way of a symmetric quinoid-like minimum. Temperature-dependent
nanosecond TAS was utilized to assess the relative stabilities of intermediates,
substantiating the observed trend in photochemical reactivity OTP > OQTP > TPB.
In total, this work demonstrates how specific structural variations alter the
course of the excited-state dynamics and photoproduct stability that underlies
desired photochemistry.
PMID- 25849257
TI - Machine learning assisted design of highly active peptides for drug discovery.
AB - The discovery of peptides possessing high biological activity is very challenging
due to the enormous diversity for which only a minority have the desired
properties. To lower cost and reduce the time to obtain promising peptides,
machine learning approaches can greatly assist in the process and even partly
replace expensive laboratory experiments by learning a predictor with existing
data or with a smaller amount of data generation. Unfortunately, once the model
is learned, selecting peptides having the greatest predicted bioactivity often
requires a prohibitive amount of computational time. For this combinatorial
problem, heuristics and stochastic optimization methods are not guaranteed to
find adequate solutions. We focused on recent advances in kernel methods and
machine learning to learn a predictive model with proven success. For this type
of model, we propose an efficient algorithm based on graph theory, that is
guaranteed to find the peptides for which the model predicts maximal bioactivity.
We also present a second algorithm capable of sorting the peptides of maximal
bioactivity. Extensive analyses demonstrate how these algorithms can be part of
an iterative combinatorial chemistry procedure to speed up the discovery and the
validation of peptide leads. Moreover, the proposed approach does not require the
use of known ligands for the target protein since it can leverage recent multi
target machine learning predictors where ligands for similar targets can serve as
initial training data. Finally, we validated the proposed approach in vitro with
the discovery of new cationic antimicrobial peptides. Source code freely
available at http://graal.ift.ulaval.ca/peptide-design/.
PMID- 25849260
TI - Germline editing: time for discussion.
PMID- 25849259
TI - Familiality of mood repair responses among youth with and without histories of
depression.
AB - Affect regulation skills develop in the context of the family environment,
wherein youths are influenced by their parents', and possibly their siblings',
regulatory responses and styles. Regulatory responses to sadness (mood repair)
that exacerbate or prolong dysphoria (maladaptive mood repair) may represent one
way in which depression is transmitted within families. We examined self-reported
adaptive and maladaptive mood repair responses across cognitive, social and
behavioural domains in Hungarian 11- to 19-year-old youth and their parents.
Offspring included 214 probands with a history of childhood-onset depressive
disorder, 200 never depressed siblings and 161 control peers. Probands reported
the most problematic mood repair responses, with siblings reporting more modest
differences from controls. Mood repair responses of parents and their offspring,
as well as within sib-pairs, were related, although results differed as a
function of the regulatory response domain. Results demonstrate familiality of
maladaptive and adaptive mood repair responses in multiple samples. These
familial associations suggest that relationships with parents and siblings within
families may impact the development of affect regulation in youth.
PMID- 25849261
TI - Reexamination casts doubt on brain tissue classified as healthy.
PMID- 25849262
TI - After flu vaccine mismatch, calls for delayed selection intensify.
PMID- 25849263
TI - Warren joins lawmakers proposing new ideas for science funding.
PMID- 25849264
TI - Questions raised about whether compulsory licenses get best prices.
PMID- 25849265
TI - New model tackles sticky problem of getting drugs past mucus.
PMID- 25849267
TI - Many returns: call-ins and breakfasts hand back results to study volunteers.
PMID- 25849268
TI - A mediator for malaria stickiness in A versus O blood.
PMID- 25849269
TI - Harnessing gene repression to inhibit leukemia.
PMID- 25849270
TI - Beta cell glutamate receptor antagonists: novel oral antidiabetic drugs?
PMID- 25849272
TI - Erratum: a next-generation dual-recombinase system for time- and host-specific
targeting of pancreatic cancer.
PMID- 25849271
TI - Intracellular chloride accumulation: a possible mechanism for cognitive deficits
in Down syndrome.
PMID- 25849273
TI - Corrigendum: Translation from a DMD exon 5 IRES results in a functional
dystrophin isoform that attenuates dystrophinopathy in humans and mice.
PMID- 25849274
TI - Corrigendum: Inhibition of JAK-STAT signaling stimulates adult satellite cell
function.
PMID- 25849275
TI - Corrigendum: Asfotase-alpha improves bone growth, mineralization and strength in
mouse models of neurofibromatosis type-1.
PMID- 25849276
TI - Erratum: De novo fatty acid synthesis controls the fate between regulatory T and
T helper 17 cells.
PMID- 25849278
TI - On the treewidths of graphs of bounded degree.
AB - In this paper, we develop a new technique to study the treewidth of graphs with
bounded degree. We show that the treewidth of a graph G = (V, E) with maximum
vertex degree d is at most [Formula: see text] for sufficiently large d, where C
is a constant.
PMID- 25849277
TI - Symportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an
essential rRNA-binding site.
AB - During 60S biogenesis, mature 5S RNP consisting of 5S RNA, RpL5 and RpL11,
assembles into a pre-60S particle, where docking relies on RpL11 interacting with
helix 84 (H84) of the 25S RNA. How 5S RNP is assembled for recruitment into the
pre-60S is not known. Here we report the crystal structure of a ternary symportin
Syo1-RpL5-N-RpL11 complex and provide biochemical and structural insights into 5S
RNP assembly. Syo1 guards the 25S RNA-binding surface on RpL11 and competes with
H84 for binding. Pull-down experiments show that H84 releases RpL11 from the
ternary complex, but not in the presence of 5S RNA. Crosslinking mass
spectrometry visualizes structural rearrangements on incorporation of 5S RNA into
the Syo1-RpL5-RpL11 complex supporting the formation of a pre-5S RNP. Our data
underline the dual role of Syo1 in ribosomal protein transport and as an assembly
platform for 5S RNP.
PMID- 25849279
TI - Divergent, stereoselective access to heterocyclic alpha,alpha-quaternary- and
beta(2,3,3)-amino acid derivatives from a N-Pmp-protected Orn-derived beta
lactam.
AB - A suitably protected Orn-derived (3S,4S)-beta-lactam was used as common
intermediate in the synthesis of conformationally constrained (3S,4S)-2
oxoazepane alpha,alpha- and (2S,3S)-2-oxopiperidine-beta(2,3,3)-amino acid
derivatives. Compared to alternative procedures using an N-p-methoxybenzyl group
at the 2-azetidinone, the incorporation of a p-methoxyphenyl moiety is crucial
for the excellent stereochemical outcomes in the preparation of these
heterocyclic amino acids. Chemoselective 7- or 6-exo-trig cyclization was
achieved through alternative sequences of Pmp-deprotection/Boc-activation,
followed by inter- and intramolecular beta-lactam ring opening, respectively.
PMID- 25849280
TI - Correction: Validation of reference housekeeping genes for gene expression
studies in western corn rootworm (Diabrotica virgifera virgifera).
PMID- 25849281
TI - Cognition and mood-related behaviors in L3mbtl1 null mutant mice.
AB - Alterations in histone lysine methylation and epigenetic regulators of gene
expression could play a role in the neurobiology and treatment of patients
diagnosed with mood spectrum disorder, including depression and anxiety.
Mutations and altered expression of various lysine methyltransferases (KMTs) and
demethylases (KDMs) have been linked to changes in motivational and emotional
behaviors in preclinical model systems. However, it is not known whether
regulators operating downstream of histone lysine methylation could affect mood
related behavior. Malignant Brain Tumor (MBT) domain 'chromatin reader' proteins
bind to methylated histone lysine residues and associate with chromatin
remodeling complexes to facilitate or repress gene expression. MBT proteins,
including the founding member, L3mbtl1, maintain high levels of expression in
neurons of the mature brain. Here, we exposed L3mbtl1 null mutant mice to a wide
range of tests exploring cognition and mood-relevant behaviors at baseline and in
the context of social isolation, as a stressor to elicit depression-related
behavior in susceptible mice. L3mbtl1 loss-of-function was associated with
significant decreases in depression and and anxiety in some of the behavioral
paradigms. This was not associated with a more generalized neurological
dysfunction because cognition and memory remained unaltered in comparison to
controls. These findings warrant further investigations on the role of MBT
chromatin reader proteins in the context of emotional and affective behaviors.
PMID- 25849283
TI - A new casbane diterpene from Euphorbia pekinensis.
AB - A new casbane diterpenoid, referred to as pekinenin G, together with one cembrane
diterpene and four known casbane diterpenoids were isolated from the roots of
Euphorbia pekinensis. Their structures were elucidated on the basis of
spectroscopic studies and comparison with related known compounds. The six
compounds showed different cytotoxic activities against four human cancer cell
lines.
PMID- 25849282
TI - Comprehensive profiling of amino acid response uncovers unique methionine
deprived response dependent on intact creatine biosynthesis.
AB - Besides being building blocks for protein synthesis, amino acids serve a wide
variety of cellular functions, including acting as metabolic intermediates for
ATP generation and for redox homeostasis. Upon amino acid deprivation, free
uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized
transcriptional amino acid response (AAR). However, it is not clear whether the
deprivation of different individual amino acids triggers identical or distinct
AARs. Here, we characterized the global transcriptional response upon deprivation
of one amino acid at a time. With the exception of glycine, which was not
required for the proliferation of MCF7 cells, we found that the deprivation of
most amino acids triggered a shared transcriptional response that included the
activation of ATF4, p53 and TXNIP. However, there was also significant
heterogeneity among different individual AARs. The most dramatic transcriptional
response was triggered by methionine deprivation, which activated an extensive
and unique response in different cell types. We uncovered that the specific
methionine-deprived transcriptional response required creatine biosynthesis. This
dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L
methionine (SAM) during creatine biosynthesis that helps to deplete SAM under
methionine deprivation and reduces histone methylations. As such, the
simultaneous deprivation of methionine and sources of creatine biosynthesis
(either arginine or glycine) abolished the reduction of histone methylation and
the methionine-specific transcriptional response. Arginine-derived ornithine was
also required for the complete induction of the methionine-deprived specific gene
response. Collectively, our data identify a previously unknown set of
heterogeneous amino acid responses and reveal a distinct methionine-deprived
transcriptional response that results from the crosstalk of arginine, glycine and
methionine metabolism via arginine/glycine-dependent creatine biosynthesis.
PMID- 25849285
TI - Morphogens Reveal the Appearance and Functions of lncRNAs.
AB - During the first meiotic division, the entire genetic information from DNA is
transcribed into mRNPs and stored in the ovoplasm in the form of mRNP particles.
The 39 human nuclear HOX proteins bind to thousands of mRNAs transcribed
repeatedly by lampbrush chromosomes. HOX proteins suppress processing and
translation. The RNP particles containing lncRNAs+HOX proteins are the morphogens
("transcription factors," more precisely differentiation factors), which unlock
new genes and differentiate the cells of the developing embryo. All ovoplasmic
mRNAs bound with HOX proteins do not translate and are noncoding. Their
destination (purpose) is transportation of HOX proteins to the complementary DNAs
and cell differentiation.
PMID- 25849284
TI - Depletion of the polyamines spermidine and spermine by overexpression of
spermidine/spermine N1-acetyltransferase 1 (SAT1) leads to mitochondria-mediated
apoptosis in mammalian cells.
AB - The polyamines putrescine, spermidine and spermine are intimately involved in the
regulation of cellular growth and viability. Transduction of human embryonic
kidney (HEK) 293T cells with an adenovirus encoding a key polyamine catabolic
enzyme, spermidine N1-acetyltransferase 1 (SSAT1)/SAT1 (AdSAT1), leads to a rapid
depletion of spermidine and spermine, arrest in cell growth and a decline in cell
viability. Annexin V/propidium iodide FACS analyses, terminal uridine nucleotide
end-labelling (TUNEL) and caspase 3 assays showed a clear indication of apoptosis
in AdSAT1-transduced cells (at 24-72 h), but not in cells transduced with GFP
encoding adenovirus (AdGFP). Apoptosis in the polyamine-depleted cells occurs by
the mitochondrial intrinsic pathway, as evidenced by loss of mitochondrial
membrane potential, increase in pro-apoptotic Bax, decrease in anti-apoptotic Bcl
xl, Bcl2 and Mcl-1 and release of cytochrome c from mitochondria, upon
transduction with AdSAT1. Moreover, TEM images of AdSAT1-transduced cells
revealed morphological changes commonly associated with apoptosis, including cell
shrinkage, nuclear fragmentation, mitochondrial alteration, vacuolization and
membrane blebbing. The apoptosis appears to result largely from depletion of the
polyamines spermidine and spermine, as the polyamine analogues alpha
methylspermidine (alpha-MeSpd) and N1,N12-dimethylspermine (Me2Spm) that are not
substrates for SAT1 could partially restore growth and prevent apoptosis of
AdSAT1-transduced cells. Inhibition of polyamine oxidases did not restore the
growth of AdSAT1-transduced cells or block apoptosis, suggesting that the growth
arrest and apoptosis were not induced by oxidative stress resulting from
accelerated polyamine catabolism. Taken together, these data provide strong
evidence that the depletion of the polyamines spermidine and spermine leads to
mitochondria-mediated apoptosis.
PMID- 25849287
TI - In situ imaging of on-surface, solvent-free molecular single-crystal growth.
AB - The formation of crystalline materials has been studied for more than a century.
Recent discoveries about the self-assembly of many inorganic materials, involving
aggregation of nanoparticle (NP) precursors or pre-nucleation clusters, challenge
the simple assumptions of classical crystallization theory. The situation for
organic materials is even more of a terra incognita due to their high complexity.
Using in situ high-temperature atomic force microscopy during the solvent-free
crystallization of an organic compound [Ni(quinolone-8-thiolate)2], we observe
long-range migration of NPs on a silica substrate and their incorporation into
larger crystals, suggesting a non-classical pathway in the growth of the
molecular crystal.
PMID- 25849286
TI - delta-tocotrienol induces human bladder cancer cell growth arrest, apoptosis and
chemosensitization through inhibition of STAT3 pathway.
AB - Vitamin E intake has been implicated in reduction of bladder cancer risk.
However, the mechanisms remain elusive. Here we reported that delta-tocotrienol
(delta-T3), one of vitamin E isomers, possessed the most potent cytotoxic
capacity against human bladder cancer cells, compared with other Vitamin E
isomers. delta-T3 inhibited cancer cell proliferation and colonogenicity through
induction of G1 phase arrest and apoptosis. Western blotting assay revealed that
delta-T3 increased the expression levels of cell cycle inhibitors (p21, p27), pro
apoptotic protein (Bax) and suppressed expression levels of cell cycle protein
(Cyclin D1), anti-apoptotic proteins (Bcl-2, Bcl-xL and Mcl-1), resulting in the
Caspase-3 activation and cleavage of PARP. Moreover, the delta-T3 treatment
inhibited ETK phosphorylation level and induced SHP-1 expression, which was
correlated with downregulation of STAT3 activation. In line with this, delta-T3
reduced the STAT3 protein level in nuclear fraction, as well as its transcription
activity. Knockdown of SHP-1 partially reversed delta-T3-induced cell growth
arrest. Importantly, low dose of delta-T3 sensitized Gemcitabine-induced
cytotoxic effects on human bladder cancer cells. Overall, our findings
demonstrated, for the first time, the cytotoxic effects of delta-T3 on bladder
cancer cells and suggest that delta-T3 might be a promising chemosensitization
reagent for Gemcitabine in bladder cancer treatment.
PMID- 25849289
TI - Contribution of Leg-Muscle Forces to Paddle Force and Kayak Speed During Maximal
Effort Flat-Water Paddling.
AB - The purpose was to investigate the contribution of leg-muscle-generated forces to
paddle force and kayak speed during maximal-effort flat-water paddling. Five
elite male kayakers at national and international level participated. The
participants warmed up at progressively increasing speeds and then performed a
maximal-effort, nonrestricted paddling sequence. This was followed after 5 min
rest by a maximal-effort paddling sequence with the leg action restricted--the
knee joints "locked." Left- and right-side foot-bar and paddle forces were
recorded with specially designed force devices. In addition, knee angular
displacement of the right and left knees was recorded with electrogoniometric
technique, and the kayak speed was calculated from GPS signals sampled at 5 Hz.
The results showed that reduction in both push and pull foot-bar forces resulted
in a reduction of 21% and 16% in mean paddle-stroke force and mean kayak speed,
respectively. Thus, the contribution of foot-bar force from lower-limb action
significantly contributes to kayakers' paddling performance.
PMID- 25849288
TI - Comparative study of the protein profiles of Sunki mandarin and Rangpur lime
plants in response to water deficit.
AB - BACKGROUND: Rootstocks play a major role in the tolerance of citrus plants to
water deficit by controlling and adjusting the water supply to meet the
transpiration demand of the shoots. Alterations in protein abundance in citrus
roots are crucial for plant adaptation to water deficit. We performed two
dimensional electrophoresis (2-DE) separation followed by LC/MS/MS to assess the
proteome responses of the roots of two citrus rootstocks, Rangpur lime (Citrus
limonia Osbeck) and 'Sunki Maravilha' (Citrus sunki) mandarin, which show
contrasting tolerances to water deficits at the physiological and molecular
levels. RESULTS: Changes in the abundance of 36 and 38 proteins in Rangpur lime
and 'Sunki Maravilha' mandarin, respectively, were observed via LC/MS/MS in
response to water deficit. Multivariate principal component analysis (PCA) of the
data revealed major changes in the protein profile of 'Sunki Maravilha' in
response to water deficit. Additionally, proteomics and systems biology analyses
allowed for the general elucidation of the major mechanisms associated with the
differential responses to water deficit of both varieties. The defense mechanisms
of Rangpur lime included changes in the metabolism of carbohydrates and amino
acids as well as in the activation of reactive oxygen species (ROS)
detoxification and in the levels of proteins involved in water stress defense. In
contrast, the adaptation of 'Sunki Maravilha' to stress was aided by the
activation of DNA repair and processing proteins. CONCLUSIONS: Our study reveals
that the levels of a number of proteins involved in various cellular pathways are
affected during water deficit in the roots of citrus plants. The results show
that acclimatization to water deficit involves specific responses in Rangpur lime
and 'Sunki Maravilha' mandarin. This study provides insights into the effects of
drought on the abundance of proteins in the roots of two varieties of citrus
rootstocks. In addition, this work allows for a better understanding of the
molecular basis of the response to water deficit in citrus. Further analysis is
needed to elucidate the behaviors of the key target proteins involved in this
response.
PMID- 25849290
TI - Inhibition of protein kinase C enhances angiogenesis induced by platelet-derived
growth factor C in hyperglycemic endothelial cells.
AB - BACKGROUND: Diabetes is a risk factor for the development of cardiovascular
diseases with impaired angiogenesis. We have previously shown that platelet
derived growth factor C (PDGF-C) and its receptor, PDGF receptor alpha (PDGFR
alpha) were downregulated in ischemic limbs of diabetic mice, although the
underlying mechanisms remained elusive. Protein kinase C (PKC) is a family of
serine/threonine kinases and is known to be involved in angiogenesis. The purpose
of this study is to elucidate the mechanisms of how PDGF-C/PDGFR-alpha axis is
impaired in diabetes. METHODS: Human umbilical vein endothelial cells (HUVECs)
and human cardiac microvascular endothelial cells (HMVECs) cultured in
normoglycemic or hyperglycemic conditions were examined. We also examined the
effects of PKC inhibition on the PDGF-C/PDGFR-alpha axis in endothelial cells
exposed to hyperglycemia. RESULTS: Hyperglycemia inhibited proliferation and
decreased viability of both HUVECs and HMVECs. Hyperglycemic endothelial cells
exhibited decreased PDGFR-alpha expression both at messenger RNA (mRNA) and
protein levels, while there was no significant change in expression of PDGF-C. We
also found that expression of PKC-alpha, one of the PKC isoforms, was increased
in hyperglycemic endothelial cells and that inhibition of PKC upregulated PDGFR
alpha expression in these cells. Phosphorylation of extracellular signal
regulated kinase (ERK) and Akt induced by PDGF-C was significantly attenuated in
hyperglycemic endothelial cells, whereas inhibition of PKC effectively reversed
these inhibitory effects. Moreover, inhibition of PKC also promoted angiogenesis
induced by PDGF-C in hyperglycemic endothelial cells, which was not observed in
vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis. CONCLUSIONS:
These findings suggest that downregulation of the PDGF-C/PDGFR-alpha axis is
involved in impaired angiogenesis of hyperglycemia through upregulation of PKC.
Targeting PKC to restore PDGF-C signaling might be a novel therapeutic strategy
for the treatment of vascular complications in diabetes.
PMID- 25849291
TI - Iron impregnated activated carbon as an efficient adsorbent for the removal of
methylene blue: regeneration and kinetics studies.
AB - In this study, iron impregnated activated carbon (FeAC) was synthesized following
an oxidation and iron impregnation of activated carbon (AC). Both the AC and FeAC
were characterized by pHZPC and FTIR spectroscopy. The removal of Methylene Blue
(MB) by AC and FeAC was examined under various experimental conditions. The FeAC
showed up to 95% (higher than AC) MB removal in the pH range of 7-10. Although
the reaction kinetics was pseudo-second order, the overall rate was controlled by
a number of processes such as film diffusion, pore diffusion and intraparticle
diffusion. The activation energy values for the MB uptake by AC and FeAC (21.79
and 14.82 kJ/mol, respectively) revealed a physisorption process. In the
regeneration study, FeAC has shown consistently >= 90% MB removal even up to 10
repeated cycles. The reusable characteristic of the spent FeAC improved the
practical use of activated carbon and can be a breakthrough for continuous flow
system applications where it can work effectively without any significant
reduction in its performance.
PMID- 25849292
TI - Biosynthesis and role of 3-methylbutanal in cheese by lactic acid bacteria: Major
metabolic pathways, enzymes involved, and strategies for control.
AB - Branched chain aldehyde, 3-methylbutanal is associated as a key flavor compound
with many hard and semi-hard cheese varieties. The presence and impact of this
flavor compound in bread, meat, and certain beverages has been recently
documented, however its presence and consequences regarding cheese flavor were
not clearly reported. This paper gives an overview of the role of 3-methylbutanal
in cheese, along with the major metabolic pathways and key enzymes leading to its
formation. Moreover, different strategies are highlighted for the control of this
particular flavor compound in specific cheese types.
PMID- 25849293
TI - The use of autologous fascia lata graft in the laparoscopic reinforcement of
large hiatal defect: initial observations of the surgical technique.
AB - BACKGROUND: Even though there is no consensus, many authors believe that in the
cases of large hiatal defects, structurally altered crura and/or absence of
peritoneal lining, a crural reinforcement should be performed. Reinforcement
could be performed with different techniques and different type of mesh, either
synthetic or biologic. The disadvantages of mesh repair include the possibility
of serious complications and increased costs especially in the usage of composite
or biologic mesh. METHODS: The study includes 10 cases of reinforced primary
suture line of the pillars with autologous fascia lata, in elective laparoscopic
repair of the giant PEH with a large hiatal defect and friable crura. After
intraopreative confirmation of the large hiatal defect (hiatal surface area of
more than 8 cm2) and friable crura, an autologous fascia lata graft was harvested
in the usual manner and placed in on-lay fashion to reinforce the pillar suture
line. We analyzed surgical technique, complications, and initial follow-up of the
patients. RESULTS: Average hiatal surface area (HSA) in our series was 10.6 cm2
(range 8.1 to 14.4 cm2). The average duration of operation was 203.9 min/3.4
hours (range 160-250 min). Except for a mild hematoma in the harvesting region
that resolved spontaneously, there were no procedure related complications and 30
days mortality rate was zero. The average postoperative length of stay was 6.5
days (5-8 days). Out of 10 patients, 5 completed the annual follow-up visit,
while 8 completed a 6- month follow-up visit. So far there is no hernia
recurrence and/or problems with swallowing function. However, one patient has
felt a mild discomfort in the harvested region that does not influence normal
daily activities. CONCLUSIONS: Autologous fascia lata graft hiatal reinforcement
represents a technically feasible, easy, and available option for the on-lay
reinforcement of large hiatal defects with friable crura in the laparoscopic
repair of giant PEHs.
PMID- 25849294
TI - Unraveling 14-3-3 proteins in C4 panicoids with emphasis on model plant Setaria
italica reveals phosphorylation-dependent subcellular localization of RS splicing
factor.
AB - 14-3-3 proteins are a large multigenic family of regulatory proteins ubiquitously
found in eukaryotes. In plants, 14-3-3 proteins are reported to play significant
role in both development and response to stress stimuli. Therefore, considering
their importance, genome-wide analyses have been performed in many plants
including Arabidopsis, rice and soybean. But, till date, no comprehensive
investigation has been conducted in any C4 panicoid crops. In view of this, the
present study was performed to identify 8, 5 and 26 potential 14-3-3 gene family
members in foxtail millet (Si14-3-3), sorghum (Sb14-3-3) and maize (Zm14-3-3),
respectively. In silico characterization revealed large variations in their gene
structures; segmental and tandem duplications have played a major role in
expansion of these genes in foxtail millet and maize. Gene ontology annotation
showed the participation of 14-3-3 proteins in diverse biological processes and
molecular functions, and in silico expression profiling indicated their higher
expression in all the investigated tissues. Comparative mapping was performed to
derive the orthologous relationships between 14-3-3 genes of foxtail millet and
other Poaceae members, which showed a higher, as well as similar percentage of
orthology among these crops. Expression profiling of Si14-3-3 genes during
different time-points of abiotic stress and hormonal treatments showed a
differential expression pattern of these genes, and sub-cellular localization
studies revealed the site of action of Si14-3-3 proteins within the cells.
Further downstream characterization indicated the interaction of Si14-3-3 with a
nucleocytoplasmic shuttling phosphoprotein (SiRSZ21A) in a phosphorylation
dependent manner, and this demonstrates that Si14-3-3 might regulate the splicing
events by binding with phosphorylated SiRSZ21A. Taken together, the present study
is a comprehensive analysis of 14-3-3 gene family members in foxtail millet,
sorghum and maize, which provides interesting information on their gene
structure, protein domains, phylogenetic and evolutionary relationships, and
expression patterns during abiotic stresses and hormonal treatments, which could
be useful in choosing candidate members for further functional characterization.
In addition, demonstration of interaction between Si14-3-3 and SiRSZ21A provides
novel clues on the involvement of 14-3-3 proteins in the splicing events.
PMID- 25849295
TI - Modelling discrete choice variables in assessment of teaching staff work
satisfaction.
AB - Levels of self-reported job satisfaction and motivation were measured by survey
in a sample of 286 teachers. Using the discrete choice framework, the paper tries
to assess the relevance of the considered indicators (demographic, social,
motivational) in overall teaching work satisfaction. The findings provide
evidence that job satisfaction is correlated significantly with level of
university degree held by the teacher, type of secondary school where the teacher
is enrolled, revenues, and salary-tasks adequacy. This is important for the
Romanian economy, since the education system is expected to provide future human
resources with enhanced skills and abilities.
PMID- 25849297
TI - Predicting malignant and tuberculous pleural effusions through demographics and
pleural fluid analysis of patients.
AB - INTRODUCTION: The differential diagnosis of malignant and tuberculous pleural
effusion is frequently difficult. OBJECTIVES: The aim of our study is to
determine the discrimination value of demographic parameters and different
biological markers in pleural fluid. METHODS: In pleural fluid obtained from 106
patients with tuberculous, 250 with malignant and 218 with miscellaneous pleural
effusion, clinical and analytical parameters were analysed, applying polytomous
regression analysis and the receiver operating characteristic (ROC) curves.
RESULTS: The three groups could be differentiated using the measured markers.
Age, tumour necrosing factor-alpha, lactate dehydrogenase (LDH), adenosine
deaminase (ADA), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were
significant predictors for discriminating tuberculous from malignant pleural
effusions; nucleated cells, lymphocytes, cholesterol, LDH, ADA, CRP, CEA and
CA15.3 distinguish between malignant and miscellaneous pleural effusions. The ROC
areas (95% confidence interval) were, 0.973 (0.953, 0.992) for tuberculous, 0.922
(0.900, 0.943) for miscellaneous, and 0.927 (0.907, 0.948) for malignant pleural
effusion. The polytomous model correctly classified a significantly high
proportion of patients with tuberculosis (85.8%) and cancer (81.6%). The
incorrect classification rate was 17.8%, which increased to 19.5% in the
correction using bootstrap. CONCLUSIONS: The results obtained to estimate the
probability of tuberculous and malignant pleural effusion confirm that this model
achieves a high diagnostic accuracy. This model should be applied to determine
which patients with a pleural effusion of unknown origin would not benefit from
further invasive procedures.
PMID- 25849296
TI - Fusarium oxysporum triggers tissue-specific transcriptional reprogramming in
Arabidopsis thaliana.
AB - Some of the most devastating agricultural diseases are caused by root-infecting
pathogens, yet the majority of studies on these interactions to date have focused
on the host responses of aerial tissues rather than those belowground. Fusarium
oxysporum is a root-infecting pathogen that causes wilt disease on several plant
species including Arabidopsis thaliana. To investigate and compare
transcriptional changes triggered by F. oxysporum in different Arabidopsis
tissues, we infected soil-grown plants with F. oxysporum and subjected root and
leaf tissue harvested at early and late timepoints to RNA-seq analyses. At least
half of the genes induced or repressed by F. oxysporum showed tissue-specific
regulation. Regulators of auxin and ABA signalling, mannose binding lectins and
peroxidases showed strong differential expression in root tissue. We demonstrate
that ARF2 and PRX33, two genes regulated in the roots, promote susceptibility to
F. oxysporum. In the leaves, defensins and genes associated with the response to
auxin, cold and senescence were strongly regulated while jasmonate biosynthesis
and signalling genes were induced throughout the plant.
PMID- 25849298
TI - Electromagnetic navigation-guided TBNA vs conventional TBNA in the diagnosis of
mediastinal lymphadenopathy.
AB - OBJECTIVES: Conventional transbronchial needle aspiration (C-TBNA) is a safe
method for the diagnosis of hilar and mediastinal lymphadenopathy (MLN). However,
diagnostic yield of this technique varies considerably. Electromagnetic
navigation bronchoscopy (ENB) is a new technology to increase the diagnostic
yield of flexible bronchoscopy for the peripheral lung lesions and MLN. The aim
of this prospective study was to compare the diagnostic and sampling success of
ENB-guided TBNA (ENB-TBNA) in comparison with C-TBNA while dealing with MLN.
METHODS: Consecutive patients with MLN were randomized into two groups - C-TBNA
and ENB-TBNA - using a computer-based number shuffling system to avoid
recruitment bias. Procedures were performed in usual fashion, published
previously. RESULTS: Ninety-four cases (M/F: 45/49) with a total of 145 stations
of MLN were enrolled in the study. In 44 patients, 81 stations were sampled by
ENB-TBNA, and in 50 patients 64 stations by C-TBNA. The mean size of MLN in study
subjects was 17.56 +/- 6.25 mm. The sampling success was significantly higher in
ENB-TBNA group (82.7%) compared with C-TBNA group (51.6%) (P < 0.005). Defined by
histopathological result, the diagnostic yield in ENB-TBNA was 72.8%, and 42.2%
with C-TBNA (P < 0.005). For subcarinal localization, sampling or diagnostic
success was higher in ENB-TBNA than that of C-TBNA (P < 0.05). Based on the size
of the MLN <=15 mm or >15 mm, the sampling success of ENB-TBNA was also
significantly higher than C-TBNA in both subgroups (P < 0.005 and P < 0.005,
respectively). No serious complication was observed. CONCLUSION: In this study
comparing ENB-TBNA and C-TBNA, the sampling and diagnostic success of ENB-TBNA
was found to be superior while dealing with MLN, in all categories studied.
PMID- 25849299
TI - The clinical utility of Memorial Symptom Assessment-Short Form and Condensed
Memorial Symptom Assessment Scale in Turkish lung cancer patients.
AB - INTRODUCTION: Symptom assessment is essential in the palliative care of patients
with cancer. We studied the Memorial Assessment Scale Test-Short Form (MSAS-SF)
and Condensed Memorial Assessment Test (CMSAS) in Turkish lung cancer patients.
MATERIAL AND METHOD: Fifty-one patients with lung cancer (47 non-small, 4 small
cell) were staged according to the International Association for the Study of
Lung Cancer 2007 and filled the MSAS-SF. Karnofsky performance status, TNM
staging, MSAS-SF and CMSAS scores were recorded. The study was approved by the
local research ethics committee. RESULTS: The mean age of 51 patients was 61.7 +/
9. Fifty-one percent were staged as M1 while 49% were staged as M0. The mean
values for global distress index, PHYS (physical symptom distress), PSYCH
(psychological symptom score) and MSAS-SUM were 1.15 +/- 0.8, 0.9 +/- 0.8, 1.13
+/- 1.03 and 0.82 +/- 0.47 in order. The mean values for CPHYS (physical symptom
distress for Condensed MSAS), CPSYCH (psychological symptom score for CMSAS) and
CSUM (sum scores) were 1.2 +/- 0.75, 1.22 +/- 1.1 and 1.16 +/- 0.69 in order.
Cronbach's alpha coefficients for MSAS-SF and CMSAS were 0.861 and 0.728 in
order. Summary scores for both MSAS-SF and CMSAS-SF were significantly higher in
patients with M1 disease than from M0 disease. In addition, PHYS and MSAS-SUM in
MSAS-SF were significantly correlated with T and N stage. The area under curve
for MSAS-SF and CMSAS were 0.793 and 0.70 in order. CONCLUSION: MSAS-SF and CMSAS
demonstrated significantly higher scores in lung cancer patients with M1 disease
than patients with M0 disease. Further studies are needed to evaluate the
usefulness of MSAS-SF and CMSAS in lung cancer patients.
PMID- 25849300
TI - Cell wall modification in tobacco by differential targeting of recombinant
endoglucanase from Trichoderma reesei.
AB - BACKGROUND: The development of transgenic plants as a production platform for
biomass-degrading enzymes is a promising tool for an economically feasible
allocation of enzymes processing lignocellulose. Previous research has already
identified a major limitation of in planta production such as interference with
the structure and integrity of the plant cell wall resulting in a negative
influence on plant growth and development. RESULTS: Here, we describe the in
planta expression of endoglucanase TrCel5A from the mesophilic fungus Trichoderma
reesei with differential intracellular targeting and evaluate its impact on the
tobacco cell wall composition. Targeting of the enzyme to the apoplast leads to
distinct changes in cell polysaccharides such as glucose level in the matrix
polysaccharides (MPS). These effects are combined with severe changes in plant
development. Retention of TrCel5A in the endoplasmic reticulum (ER) could avoid
visible effects on plant growth under the chosen conditions, but exhibits changes
in the composition of the MPS. CONCLUSIONS: These results give new insights into
the complex interaction of heterologous cellulase expression with cell wall
development and it outlines novel promising strategies to engineer plant cell
walls for improved biomass processing.
PMID- 25849301
TI - The RGS2 (-391, C>G) genetic variation correlates to antihypertensive drug
responses in Chinese patients with essential hypertension.
AB - OBJECTIVE: Regulators of G-protein signaling protein 2 (RGS2) play an
irreplaceable role in the control of normal blood pressure (BP). One RGS2 (-391,
C>G) genetic variation markedly changes its mRNA expression levels. This study
explored the relationship between this genetic variation and the responses to
antihypertensive drugs in Chinese patients with essential hypertension. METHODS:
Genetic variations of RGS2 were successfully identified in 367 specimens using
polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
assays. All patients were treated with conventional doses of antihypertensives
after a 2-week run-in period and followed-up according to our protocol. A general
linear model multivariate analysis of variance (ANOVA) was used for the data
analysis. RESULTS: A significant difference in the mean systolic BP change was
observed between RGS2 (-391, C>G) CC/CG (n = 82) and GG (n = 38) genotype
carriers (-13.6 vs. -19.9 mmHg, P = 0.043) who were treated with candesartan,
irbesartan or imidapril at the end of 6 weeks. In addition, the patients' BP
responses to alpha,beta-adrenergic receptor blockers exhibited an age-specific
association with the RGS2 (-391, C>G) genetic variation at the end of 4 weeks.
CONCLUSION: The RGS2 (-391, C>G) genetic polymorphism may serve as a biomarker to
predict a patient's response to antihypertensive drug therapy, but future studies
need to confirm this.
PMID- 25849302
TI - Decomposition of N-chloroglycine in alkaline aqueous solution: kinetics and
mechanism.
AB - The decomposition kinetics and mechanism of N-chloroglycine (MCG) was studied
under very alkaline conditions ([OH(-)] = 0.01-0.10 M). The absorbance change is
consistent with two consecutive first-order processes in the 220-350 nm
wavelength range. The first reaction is linearly dependent on [OH(-)] and
interpreted by the formation of a carbanion from MCG in an equilibrium step (KOH)
and a subsequent loss of chloride ion from this intermediate: kobs1 = KOH k1 =
(6.4 +/- 0.1) * 10(-2) M(-1) s(-1), I = 1.0 M (NaClO4), and T = 25.0 degrees C.
The second process is assigned to the first-order decomposition of N
oxalylglycine, which is also formed as an intermediate in this system: kobs2 =
(1.2 +/- 0.1) * 10(-3) s(-1). Systematic (1)H and (13)C NMR measurements were
performed in order to identify and follow the concentration changes of the
reactant, intermediate, and product. It is confirmed that the decomposition
proceeds via the formation of glyoxylate ion and produces N-formylglycine as a
final product. This compound is stable for an extended period of time but
eventually hydrolyses into formate and glycinate ions. A detailed mechanism is
postulated which resolves the controversies found in earlier literature results.
PMID- 25849303
TI - Cdx2 polymorphism affects the activities of vitamin D receptor in human breast
cancer cell lines and human breast carcinomas.
AB - Vitamin D plays a role in cancer development and acts through the vitamin D
receptor (VDR). It regulates the action of hormone responsive genes and is
involved in cell cycle regulation, differentiation and apoptosis. VDR is a
critical component of the vitamin D pathway and different common single
nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an
important role in breast cancer, modulating the activity of VDR. The objective of
this study is to assess the relationship between the Cdx2 VDR polymorphism and
the activities of VDR in human breast cancer cell lines and carcinomas breast
patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D
treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T
47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA
MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore,
the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers
used in clinical management of breast cancer was assessed in an ad hoc set of
breast cancer cases. Vitamin D treatment efficacy was found to be strongly
dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested.
In our series of breast cancer cases, the results indicated that patients with
variant homozygote AA were associated with bio-pathological characteristics
typical of more aggressive tumours, such as ER negative, HER2 positive and G3.
Our results may suggest a potential effect of Cdx2 VDR polymorphism on the
efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen
receptor negative). These results suggest that Cdx2 polymorphism may be a
potential biomarker for vitamin D treatment in breast cancer, independently of
the VDR receptor expression.
PMID- 25849304
TI - The ageing shift worker: a prospective cohort study on need for recovery,
disability, and retirement intentions.
AB - OBJECTIVES: This study investigates whether different shift work schedules,
compared to day work, are associated with need for recovery (NFR), future
disability, and retirement intentions for employees employed within different
economic sectors over the course of their careers. Shift work exposure duration
and the healthy worker effect are also examined. METHODS: Data from the
prospective Maastricht Cohort Study was used. Subsamples of industry (N=1877, all
men) and healthcare (N=818, 624 women and 194 men) workers were separately
investigated. GEE and Cox regression analyses were performed to investigate NFR
longitudinally. Future disability was investigated using Cox regression, and
retirement intentions were investigated using logistic regression analysis.
RESULTS: Three-shift industry workers were at risk of becoming a case of elevated
NFR during follow-up, compared to industry day workers. Three- and five-shift
industry workers were at risk for future disability. In healthcare, irregular
shift work was a risk factor for disability among older shift workers. No
significant results were found regarding retirement intentions. Findings were
probably an underestimation as exposure duration to shift work and the healthy
worker effect affected the results. CONCLUSIONS: Shift work was associated with
higher levels of NFR and a higher risk of disability. However, shift work is a
multifaceted concept as different types of shift work schedules are differently
associated with these outcomes. Different shift work types exist and shift work
schedules allow for optimization, indicating that measures to prevent adverse
outcomes should be tailored for different types of shift work and over the course
of the work career.
PMID- 25849305
TI - Transition from near-field thermal radiation to phonon heat conduction at sub
nanometre gaps.
AB - When the separation of two surfaces approaches sub-nanometre scale, the boundary
between the two most fundamental heat transfer modes, heat conduction by phonons
and radiation by photons, is blurred. Here we develop an atomistic framework
based on microscopic Maxwell's equations and lattice dynamics to describe the
convergence of these heat transfer modes and the transition from one to the
other. For gaps >1 nm, the predicted conductance values are in excellent
agreement with the continuum theory of fluctuating electrodynamics. However, for
sub-nanometre gaps we find the conductance is enhanced up to four times compared
with the continuum approach, while avoiding its prediction of divergent
conductance at contact. Furthermore, low-frequency acoustic phonons tunnel
through the vacuum gap by coupling to evanescent electric fields, providing
additional channels for energy transfer and leading to the observed enhancement.
When the two surfaces are in or near contact, acoustic phonons become dominant
heat carriers.
PMID- 25849306
TI - Cross-Linking the Surface of Cured Polydimethylsiloxane via Hyperthemal Hydrogen
Projectile Bombardment.
AB - Cross-linking of polydimethylsiloxane (PDMS) is increasingly important with
recent focus on its top surface stiffness. In this paper, we demonstrate that
hyperthermal hydrogen projectile bombardment, a surface sensitive cross-linking
technology, is superior in enhancing the mechanical properties of a cured PDMS
surface without significantly degrading its hydrophobicity. Both water contact
angle measurements and time-of-flight secondary ion mass spectrometry are used to
investigate the variations in surface chemistry and structure upon cross-linking.
Using nanoindentation and atomic force microscopy, we confirm that the thickness
of the cross-linked PDMS is controllable by the bombardment time, which opens
opportunities for tuning cross-linking degree in compliance with arising
requirements from the practice.
PMID- 25849307
TI - NMR Analysis of Tuning Cross-Strand Phe/Tyr/Trp-Trp Interactions in Designed beta
Hairpin Peptides: Terminal Switch from L to D Amino Acid as a Strategy for beta
Hairpin Capping.
AB - Interaction among the side chains of aromatic amino acids is a well-known
mechanism of protein and peptide structure stabilization, particularly in beta
sheets. Using short beta-hairpin models bearing the sequence Ac-Leu-Xxx-Val-DPro
Gly-Leu-Trp-Val-NH2, we report the surprising observation of significant
destabilization in aryl-tryptophan interactions, which results in poorly folded
peptide populations accompanied by lowering of stability. We find that such
destabilization arises from forced occupancy of the indole ring in the shielded
Edge position, in T-shaped aryl geometries. We demonstrate that this
destabilizing effect can be efficiently salvaged by replacing the N-terminal LLeu
with DLeu, which causes an increase in the folded hairpin population, while
retaining Trp in the Edge position. Our observation of unique cross strand NOEs
and data from temperature-dependent NMR and CD measurements reveals the formation
of a locally stabilized aliphatic-aromatic network, leading to an overall
increase in DeltaGF degrees by ~ -0.6 to -1.2 kcal/mol. Our results suggest that
a contextual evaluation of stabilization by tryptophan is necessary in beta
hairpins. Furthermore, we report for the first time that the use of D isomers of
aliphatic amino acids at the terminus is stabilizing, which can serve as a new
strategy for increasing beta-hairpin stability.
PMID- 25849308
TI - Type 2 Diabetes Patients' Needs and Preferences for Care Concerning Sexual
Problems: A Cross-Sectional Survey and Qualitative Interviews.
AB - Sexual dysfunction is highly prevalent among patients with type 2 diabetes;
however, little is known regarding these patients' needs and preferences for care
for sexual problems. A cross-sectional survey and 25 semistructured interviews
were therefore conducted among 40- to 75-year-old type 2 diabetes patients to
explore this. We learned from the survey and interviews that most participants
were unaware of the association between type 2 diabetes and sexual problems.
Although certain barriers for discussing sexual problems with a care provider
were identified (e.g., feelings of embarrassment), patients still reported a need
for discussing their problems, because sex was viewed as an important part of
their relationship. Some patients had sought help, but were dissatisfied with the
offered care. Patients experienced a lack of attention and information from
diabetes care providers. Improving this, together with a care provider-initiated
conversation, was suggested to lower the threshold for discussion. Moreover,
patients preferred a care provider with whom they have a close relationship,
whereas age, gender, and medical specialty were regarded to be less important. An
important recommendation was to make care for sexual problems an integral part of
routine diabetes care. Future research should look into these recommendations.
PMID- 25849309
TI - Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents
in breast cancer cells.
AB - Triple negative breast cancer cell lines have been reported to be resistant to
the cyotoxic effects of temozolomide (TMZ). We have shown previously that a novel
protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2)
has a role in the repair of estrogen-induced abasic sites. Our present study
provides evidence that downregulation of hPMC2 in MDA-MB-231 and MDA-MB-468
breast cancer cells treated with temozolomide (TMZ) decreases cell survival. This
increased sensitivity to TMZ is associated with an increase in number of
apurinic/apyrimidinic (AP) sites in the DNA. We also show that treatment with
another alkylating agent, BCNU, results in an increase in AP sites and decrease
in cell survival. Quantification of western blot analyses and immunofluorescence
experiments reveal that treatment of hPMC2 downregulated cells with TMZ results
in an increase in gamma-H2AX levels, suggesting an increase in double strand DNA
breaks. The enhancement of DNA double strand breaks in TMZ treated cells upon
downregulation of hPCM2 is also revealed by the comet assay. Overall, we provide
evidence that downregulation of hPMC2 in breast cancer cells increases
cytotoxicity of alkylating agents, representing a novel mechanism of treatment
for breast cancer. Our data thus has important clinical implications in the
management of breast cancer and brings forth potentially new therapeutic
strategies.
PMID- 25849310
TI - Food, stress, and circulating testosterone: Cue integration by the testes, not
the brain, in male zebra finches (Taeniopygia guttata).
AB - Food abundance is closely associated with reproductive readiness in vertebrates.
Food scarcity can activate the hypothalamo-pituitary-adrenal axis, decrease sex
steroid secretion, and dampen reproductive behavior. However, the mechanisms
underlying these transient effects are unclear. Gonadotropin inhibitory hormone
(GnIH), a neuropeptide present in the brain and gonads, is also influenced by
glucocorticoids and fasting in some species. We investigated whether fasting
stress activated the GnIH system in zebra finches (Taeniopygia guttata), with the
potential for downstream effects on reproductive physiology and behavior. We
fasted or fed males ad libitum for 10h. Fasting increased corticosterone and
decreased testosterone in circulation. To assess whether the decrease in
testosterone was mediated by changes in the hypothalamus and/or the gonads, we
(1) quantified GnRH- and GnIH-positive neurons in the hypothalamus, (2) assessed
hypothalamic gene expression for GnRH and GnIH, and (3) examined gene expression
for proteins involved in testosterone synthesis in fasted and control birds. No
measure of hypothalamic neuropeptides was related to treatment or circulating
steroids. However, birds with higher corticosterone had higher testicular GnIH
expression and lower testosterone. StAR and LHR expression were lower in the
testes of fasted birds than controls. Thus, the decrease in testosterone was not
likely mediated by hypothalamic GnIH, but rather by direct actions of fasting
and/or corticosterone on the testes, indicating that the testes can integrate and
respond to cues of stress directly. Such local inhibition of testosterone
synthesis may allow for rapid and reversible changes in physiology and behavior
when conditions are inappropriate for breeding.
PMID- 25849311
TI - 2-Methyl-4-chlorophenoxyacetic acid and bromoxynil herbicide death.
AB - CASE REPORT: We report a fatal case of a 37 year old gentleman who ingested a
MCPA/bromoxynil co-formulation herbicide. Although clinically well on initial
examination, our patient declined dramatically over his 18 h admission with
increasing CO2 production, hyperthermia and metabolic derangement to eventually
die from cardiac asystole 20 h post ingestion. Two hours after ingestion the MCPA
concentration was 83.9 MUg/mL and bromoxynil concentration was 137 MUg/mL.
DISCUSSION: The patients' mechanism of death appeared to be uncoupling of
oxidative phosphorylation, excess CO2 production and hyperthermia. There is
limited knowledge on the acute toxicity of these herbicides, in particular
bromoxynil, and this case highlights the relentless progression of severe
toxicity in humans.
PMID- 25849312
TI - beta-D-2'-C-Methyl-2,6-diaminopurine Ribonucleoside Phosphoramidates are Potent
and Selective Inhibitors of Hepatitis C Virus (HCV) and Are Bioconverted
Intracellularly to Bioactive 2,6-Diaminopurine and Guanosine 5'-Triphosphate
Forms.
AB - The conversion of selected beta-D-2,6-diaminopurine nucleosides (DAPNs) to their
phosphoramidate prodrug (PD) substantially blocks the conversion to the G-analog
allowing for the generation of two bioactive nucleoside triphosphates (NTPs) in
human hepatocytes. A variety of 2'-C-methyl DAPN-PDs were prepared and evaluated
for inhibition of HCV viral replication in Huh-7 cells, cytotoxicity in various
cell lines, and cellular pharmacology in both Huh-7 and primary human liver
cells. The DAPN-PDs were pan-genotypic, effective against various HCV resistant
mutants, and resistant variants could not be selected. 2'-C-Me-DAPN-TP and 2'-C
Me-GTP were chain terminators for genotype 1b HCV-pol, and single nucleotide
incorporation assays revealed that 2'-C-Me-DAPN-TP was incorporated opposite U.
No cytotoxicity was observed with our DAPN-PD when tested up to 50 MUM. A novel,
DAPN-PD, 15c, has been selected for further evaluation because of its good
virologic and toxicologic profile and its ability to deliver two active
metabolites, potentially simplifying HCV treatment.
PMID- 25849313
TI - Nox-2 up-regulation and platelet activation: Novel insights.
AB - Platelet activation is a key step in the onset of cardiovascular complications in
patients affected by systemic atherosclerosis. Among other mechanisms, oxidative
stress seems to play a crucial role in platelet activation. Reactive Oxidant
Species (ROS) including O2(-), OH(-) or H2O2 act as second messenger to activate
platelets via (1) calcium mobilization, (2) nitric oxide inactivation and (3)
through the interaction with arachidonic acid to give formation of isoprostanes.
One important source of ROS is represented by platelet NADPH oxidase. Growing
data from experimental and clinical studies provide evidence that Nox2, the
catalytic core of the NADPH oxidase system, is implicated in platelet activation.
Accordingly, an impaired platelet activation has been described in patients with
genetically determined Nox2 deficiency. Moreover, platelets added with specific
inhibitors of Nox2 revealed impaired platelet activation, along with ROS down
production. Similar results were seen in animals treated with apocynin, a Nox
inhibitor, showed reduced platelet adhesion and atherosclerotic plaque. A
significant association between Nox2 and platelet activation has been detected in
patients with atherosclerotic diseases. The observed up-regulation of Nox2 with
subsequent isoprostanes over-production in patients with cardiovascular diseases
suggests the need to explore the potential benefit of targeting Nox2 as part of a
holist anti-atherothrombotic strategy in patients with systemic atherosclerosis.
PMID- 25849314
TI - Co-solvents as stabilizing agents during heterologous overexpression in
Escherichia coli - application to chlamydial penicillin-binding protein 6.
AB - Heterologous overexpression of foreign proteins in Escherichia coli often leads
to insoluble aggregates of misfolded inactive proteins, so-called inclusion
bodies. To solve this problem use of chaperones or in vitro refolding procedures
are the means of choice. These methods are time consuming and cost intensive, due
to additional purification steps to get rid of the chaperons or the process of
refolding itself. We describe an easy to use lab-scale method to avoid formation
of inclusion bodies. The method systematically combines use of co-solvents,
usually applied for in vitro stabilization of biologicals in biopharmaceutical
formulation, and periplasmic expression and can be completed in one week using
standard equipment in any life science laboratory. Demonstrating the unique power
of our method, we overproduced and purified for the first time an active
chlamydial penicillin-binding protein, demonstrated its function as penicillin
sensitive DD-carboxypeptidase and took a major leap towards understanding the
"chlamydial anomaly."
PMID- 25849315
TI - Prevalence study and genetic typing of bovine viral diarrhea virus (BVDV) in four
bovine species in China.
AB - To determine the nationwide status of persistent BVDV infection in different
bovine species in China and compare different test methods, a total of 1379 serum
samples from clinical healthy dairy cattle, beef cattle, yaks (Bos grunniens),
and water buffalo (Bubalus bubalis) were collected in eight provinces of China
from 2010 to 2013. The samples were analyzed using commercial antibody (Ab) and
antigen (Ag) detection kits, and RT-PCR based on the 5'-UTR and Npro gene
sequencing. Results showed that the overall positive rates for BVDV Ab, Ag and RT
PCR detection were 58.09% (801/1379), 1.39% (14/1010), and 22.64% (146/645),
respectively, while the individual positive rates varied among regions, species,
and farms. The average Ab-positive rates for dairy cattle, beef cattle, yaks, and
water buffalo were 89.49% (298/333), 63.27% (248/392), 45.38% (236/520), and
14.18% (19/134), respectively, while the Ag-positive rates were 0.00% (0/116),
0.77% (3/392), 0.82% (3/368), and 5.97% (8/134), respectively, and the nucleic
acid-positive rates detected by RT-PCR were 32.06% (42/131), 13.00% (26/200),
28.89% (52/180), and 19.40% (26/134), respectively. In addition, the RT-PCR
products were sequenced and 124 5'-UTR sequences were obtained. Phylogenetic
analysis of the 5'-UTR sequences indicated that all of the 124 BVDV-positive
samples were BVDV-1 and subtyped into either BVDV-1b (33.06%), BVDV-1m (49.19%),
or a new cluster, designated as BVDV-1u (17.74%). Phylogenetic analysis based on
Npro sequences confirmed this novel subtype. In conclusion, this study revealed
the prevalence of BVDV-1 in bovine species in China and the dominant subtypes.
The high proportion of bovines with detectable viral nucleic acids in the sera,
even in the presence of high Ab levels, revealed a serious threat to bovine
health.
PMID- 25849316
TI - The measurement of amylase in drain fluid for the detection of pancreatic fistula
after gastric cancer surgery: an interim analysis.
AB - BACKGROUND: Pancreatic fistula is still one of the most serious and potential
complications after D2-D3 distal and total gastrectomy (4% to 6%). Despite their
importance, pancreatic fistulas still have not been uniformly defined. Amylase
concentration of the drainage fluid after surgery for gastric cancer can be
considered as a predictive factor of the presence of pancreatic fistula. METHODS:
From January 2009 to April 2013, 53 patients underwent surgery for gastric
cancer. Amylase concentration in the drainage fluid was measured on the first
postoperative day and if it was >=1,000 UI, it was measured again on the third
postoperative day. Pancreatic fistula occurred in four cases (7.5%). Pancreatic
fistulas were classified using the International Study Group on Pancreatic
Fistula (ISGPF) criteria into different grades of severity. Two fistulas were
Grade A, one was Grade B, and one was Grade C. RESULTS: Management of drainage
tubes is still crucial after gastrectomy, not only for the likelihood of
anastomotic leaks but also the eventual diagnosis and management of pancreatic
fistula. High amylase drainage content and then the presence of the pancreatic
fistula may be due to several causes: the operation itself when it includes
splenectomy or pancreatic tail-splenectomy, the extended lymphadenectomy but even
the 'gently and softly' pancreatic manipulation, according literature, may be a
risk factor. CONCLUSIONS: The authors assessed amylase concentration in the
drainage fluid collected from the left subphrenic cavity on POD1 and POD3 in 53
patients who had undergone curative gastrectomy for cancer and concluded that
amylase drainage content >3 times the serum amylase was a useful predictive risk
factor for pancreatic fistula. Our work is an interim analysis and the aim of
this study is to increase the accrual of the number of patients to have a
significant number. For this reason, a protocol for a multicenter trial will be
designed to verify whether the systematic measurement of amylase in drain fluid
is better than abdominal ultrasound for the detection of pancreatic fistula after
gastric cancer surgery.
PMID- 25849317
TI - Responses of two scleractinian corals to cobalt pollution and ocean
acidification.
AB - The effects of ocean acidification alone or in combination with warming on coral
metabolism have been extensively investigated, whereas none of these studies
consider that most coral reefs near shore are already impacted by other natural
anthropogenic inputs such as metal pollution. It is likely that projected ocean
acidification levels will aggravate coral reef health. We first investigated how
ocean acidification interacts with one near shore locally abundant metal on the
physiology of two major reef-building corals: Stylophora pistillata and Acropora
muricata. Two pH levels (pHT 8.02; pCO2 366 MUatm and pHT 7.75; pCO2 1140 MUatm)
and two cobalt concentrations (natural, 0.03 MUg L-1 and polluted, 0.2 MUg L-1)
were tested during five weeks in aquaria. We found that, for both species, cobalt
input decreased significantly their growth rates by 28% while it stimulated their
photosystem II, with higher values of rETRmax (relative Electron Transport Rate).
Elevated pCO2 levels acted differently on the coral rETRmax values and did not
affect their growth rates. No consistent interaction was found between pCO2
levels and cobalt concentrations. We also measured in situ the effect of higher
cobalt concentrations (1.06 +/- 0.16 MUg L-1) on A. muricata using benthic
chamber experiments. At this elevated concentration, cobalt decreased
simultaneously coral growth and photosynthetic rates, indicating that the toxic
threshold for this pollutant has been reached for both host cells and
zooxanthellae. Our results from both aquaria and in situ experiments, suggest
that these coral species are not particularly sensitive to high pCO2 conditions
but they are to ecologically relevant cobalt concentrations. Our study reveals
that some reefs may be yet subjected to deleterious pollution levels, and even if
no interaction between pCO2 levels and cobalt concentration has been found, it is
likely that coral metabolism will be weakened if they are subjected to additional
threats such as temperature increase, other heavy metals, and eutrophication.
PMID- 25849318
TI - Time and Space resolved Methods: general discussion.
PMID- 25849319
TI - Native American ancestry leads to complexity in 5-HTTLPR polymorphism association
studies.
PMID- 25849322
TI - Copper(I)-catalyzed intramolecular hydroalkoxylation of unactivated alkenes.
AB - A Cu(I)-Xantphos system catalyzed the intramolecular hydroalkoxylation of
unactivated terminal alkenes, giving five- and six-membered ring ethers. This
system is applicable to both primary and secondary alcohols. A reaction pathway
involving the addition of the Cu-O bond across the C-C double bond is proposed. A
chiral Cu(I) catalyst system based on the (R)-DTBM-SEGPHOS ligand promoted
enantioselective reaction with moderate enantioselectivity.
PMID- 25849320
TI - FKBP51 inhibits GSK3beta and augments the effects of distinct psychotropic
medications.
AB - Psychotropic medications target glycogen synthase kinase 3beta (GSK3beta), but
the functional integration with other factors relevant for drug efficacy is
poorly understood. We discovered that the suggested psychiatric risk factor FK506
binding protein 51 (FKBP51) increases phosphorylation of GSK3beta at serine 9
(pGSK3beta(S9)). FKBP51 associates with GSK3beta mainly through its FK1 domain;
furthermore, it also changes GSK3beta's heterocomplex assembly by associating
with the phosphatase PP2A and the kinase cyclin-dependent kinase 5. FKBP51 acts
through GSK3beta on the downstream targets Tau, beta-catenin and T-cell
factor/lymphoid enhancing factor (TCF/LEF). Lithium and the antidepressant (AD)
paroxetine (PAR) functionally synergize with FKBP51, as revealed by reporter gene
and protein association analyses. Deletion of FKBP51 blunted the PAR- or lithium
induced increase in pGSK3beta(S9) in cells and mice and attenuated the behavioral
effects of lithium treatment. Clinical improvement in depressive patients was
predicted by baseline GSK3beta pathway activity and by pGSK3beta(S9) reactivity
to ex vivo treatment of peripheral blood mononuclear lymphocytes with lithium or
PAR. In sum, FKBP51-directed GSK3beta activity contributes to the action of
psychotropic medications. Components of the FKBP51-GSK3beta pathway may be useful
as biomarkers predicting AD response and as targets for the development of novel
ADs.
PMID- 25849321
TI - Genes with de novo mutations are shared by four neuropsychiatric disorders
discovered from NPdenovo database.
AB - Currently, many studies on neuropsychiatric disorders have utilized massive trio
based whole-exome sequencing (WES) and whole-genome sequencing (WGS) to identify
numerous de novo mutations (DNMs). Here, we retrieved 17,104 DNMs from 3555 trios
across four neuropsychiatric disorders: autism spectrum disorder, epileptic
encephalopathy, intellectual disability and schizophrenia, in addition to
unaffected siblings (control), from 36 studies by WES/WGS. After eliminating non
exonic variants, we focused on 3334 exonic DNMs for evaluation of their
association with these diseases. Our results revealed a higher prevalence of DNMs
in the probands of all four disorders compared with the one in the controls
(P<1.3 * 10(-7)). The elevated DNM frequency is dominated by loss-of
function/deleterious single-nucleotide variants and frameshift indels (that is,
extreme mutations, P<4.5 * 10(-5)). With extensive annotation of these 'extreme'
mutations, we prioritized 764 candidate genes in these four disorders. A combined
analysis of Gene Ontology, microRNA targets and transcription factor targets
revealed shared biological process and non-coding regulatory elements of
candidate genes in the pathology of neuropsychiatric disorders. In addition,
weighted gene co-expression network analysis of human laminar-specific
neocortical expression data showed that candidate genes are convergent on eight
shared modules with specific layer enrichment and biological process features.
Furthermore, we identified that 53 candidate genes are associated with more than
one disorder (P<0.000001), suggesting a possibly shared genetic etiology
underlying these disorders. Particularly, DNMs of the SCN2A gene are frequently
occurred across all four disorders. Finally, we constructed a freely available
NPdenovo database, which provides a comprehensive catalog of the DNMs identified
in neuropsychiatric disorders.
PMID- 25849324
TI - DMF Dimethyl Acetal as Carbon Source for alpha-Methylation of Ketones: A
Hydrogenation-Hydrogenolysis Strategy of Enaminones.
AB - A novel heterogeneous catalytic hydrogenation-hydrogenolysis strategy has been
developed for the alpha-methylation of ketones via enaminones using DMF dimethyl
acetal as carbon source. This strategy provides a very convenient route to alpha
methylated ketones using a variety of ketones without any base or oxidant.
PMID- 25849323
TI - 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's
disease.
AB - BACKGROUND AND PURPOSE: Wilson's disease (WD), also known as hepatoleticular
degeneration (HLD), is a rare autosomal recessive genetic disorder of copper
metabolism, which causes copper to accumulate in body tissues. In this study,
rats fed with copper-laden diet are used to render the clinical manifestations of
WD, and their copper toxicity-induced organ lesions are studied. To investigate
metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for
treating copper-laden rats as this chelating agent could eliminate excess copper
through the urine. To date, there has been limited metabolomics study on WD,
while metabolic impacts of copper accumulation and PA administration have yet to
be established. MATERIALS AND METHODS: A combination of 1HNMR spectroscopy and
multivariate statistical analysis was applied to examine the metabolic profiles
of the urine and blood serum samples collected from the copper-laden rat model of
WD with PA treatment. RESULTS: Copper accumulation in the copper-laden rats is
associated with increased lactate, creatinine, valine and leucine, as well as
decreased levels of glucose and taurine in the blood serum. There were also
significant changes in p-hydroxyphenylacetate (p-HPA), creatinine, alpha
ketoglutarate (alpha-KG), dimethylamine, N-acetylglutamate (NAG), N
acetylglycoprotein (NAC) in the urine of these rats. Notably, the changes in p
HPA, glucose, lactate, taurine, valine, leucine, and NAG were found reversed
following PA treatment. Nevertheless, there were no changes for dimethylamine,
alpha-KG, and NAC as a result of the treatment. Compared with the controls, the
concentrations of hippurate, formate, alanine, and lactate were changed when PA
was applied and this is probably due to its side effect. A tool named SMPDB
(Small Molecule Pathway Database) is introduced to identify the metabolic pathway
influenced by the copper-laden diet. CONCLUSION: The study has shown the
potential application of NMR-based metabolomic analysis in providing further
insights into the molecular mechanism underlying disorder due to WD.
PMID- 25849325
TI - Modeling net ecosystem carbon exchange of alpine grasslands with a satellite
driven model.
AB - Estimate of net ecosystem carbon exchange (NEE) between the atmosphere and
terrestrial ecosystems, the balance of gross primary productivity (GPP) and
ecosystem respiration (Reco) has significant importance for studying the regional
and global carbon cycles. Using models driven by satellite data and climatic data
is a promising approach to estimate NEE at regional scales. For this purpose, we
proposed a semi-empirical model to estimate NEE in this study. In our model, the
component GPP was estimated with a light response curve of a rectangular
hyperbola. The component Reco was estimated with an exponential function of soil
temperature. To test the feasibility of applying our model at regional scales,
the temporal variations in the model parameters derived from NEE observations in
an alpine grassland ecosystem on Tibetan Plateau were investigated. The results
indicated that all the inverted parameters exhibit apparent seasonality, which is
in accordance with air temperature and canopy phenology. In addition, all the
parameters have significant correlations with the remote sensed vegetation
indexes or environment temperature. With parameters estimated with these
correlations, the model illustrated fair accuracy both in the validation years
and at another alpine grassland ecosystem on Tibetan Plateau. Our results also
indicated that the model prediction was less accurate in drought years, implying
that soil moisture is an important factor affecting the model performance.
Incorporating soil water content into the model would be a critical step for the
improvement of the model.
PMID- 25849326
TI - Crop-ecology and nutritional variability influence growth and secondary
metabolites of Stevia rebaudiana Bertoni.
AB - BACKGROUND: Plant nutrition and climatic conditions play important roles on the
growth and secondary metabolites of stevia (Stevia rebaudiana Bertoni); however,
the nutritional dose is strongly governed by the soil properties and climatic
conditions of the growing region. In northern India, the interactive effects of
crop ecology and plant nutrition on yield and secondary metabolites of stevia are
not yet properly understood. Thus, a field experiment comprising three levels of
nitrogen, two levels of phosphorus and three levels of potassium was conducted at
three locations to ascertain whether the spatial and nutritional variability
would dominate the leaf yield and secondary metabolites profile of stevia.
RESULTS: Principal component analysis (PCA) indicates that the applications of 90
kg N, 40 kg P2O5 and 40 kg K2O ha-1 are the best nutritional conditions in terms
of dry leaf yield for CSIR-IHBT (Council of Scientific and Industrial Research-
Institute Himalayan Bioresource Technology) and RHRS (Regional Horticultural
Research Station) conditions. The spatial variability also exerted considerable
effect on the leaf yield and stevioside content in leaves. Among the three
locations, CSIR-IHBT was found most suitable in case of dry leaf yield and
secondary metabolites accumulation in leaves. CONCLUSIONS: The results suggest
that dry leaf yield and accumulation of stevioside are controlled by the
environmental factors and agronomic management; however, the accumulation of
rebaudioside-A (Reb-A) is not much influenced by these two factors. Thus, leaf
yield and secondary metabolite profiles of stevia can be improved through the
selection of appropriate growing locations and proper nutrient management.
PMID- 25849328
TI - The Quebec rural emergency department project: a cross-sectional study of a
potential two-pronged strategy in the knowledge transfer process.
AB - INTRODUCTION: Health services research generates useful knowledge. Promotion of
implementation of this knowledge in medical practice is essential. Prior to
initiation of a major study on rural emergency departments (EDs), we deployed two
knowledge transfer strategies designed to generate interest and engagement from
potential knowledge users. The objective of this paper was to review: 1) a
combined project launch and media press release strategy, and 2) a pre-study
survey designed to survey potential knowledge users' opinions on the proposed
study variables. MATERIALS AND METHODS: We evaluated the impact of the project
launch (presentation at two conferences hosted by key stakeholders) and media
press release via a survey of participants/stakeholders and by calculating the
number of media interview requests and reports generated. We used a pre-study
survey to collect potential key stakeholder' opinions on the study variables.
RESULTS: Twenty-one of Quebec's 26 rural EDs participated in the pre-study survey
(81% participation rate). The press release about the study generated 51 press
articles and 20 media request for interviews, and contributed to public awareness
of a major rural research initiative. In the pre-study survey, thirteen
participants (46%) mentioned prior knowledge of the research project. Results
from the pre-study survey revealed that all of the potential study variables were
considered to be relevant for inclusion in the research project. Respondents also
proposed additional variables of interest, including factors promoting retention
of human resources. CONCLUSIONS: The present study demonstrated the potential
utility of a two-pronged knowledge transfer strategy, including a combined formal
launch and press release, and a pre-study survey designed to ensure that the
included variables were of interest to participants and stakeholders.
PMID- 25849329
TI - In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent
acetylcholinesterase and butyrylcholinesterase inhibitor.
AB - Vasicine (VAS), a potential natural cholinesterase inhibitor, exhibited promising
anticholinesterase activity in preclinical models and has been in development for
treatment of Alzheimer's disease. This study systematically investigated the in
vitro and in vivo metabolism of VAS in rat using ultra performance liquid
chromatography combined with electrospray ionization quadrupole time-of-flight
mass spectrometry. A total of 72 metabolites were found based on a detailed
analysis of their 1H- NMR and 13C NMR data. Six key metabolites were isolated
from rat urine and elucidated as vasicinone, vasicinol, vasicinolone, 1,2,3,9
tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, 9-oxo-1,2,3,9
tetrahydropyrrolo [2,1-b] quinazolin-3-yl hydrogen sulfate, and 1,2,3,9
tetrahydropyrrolo [2,1-b] quinazolin-3-beta-D-glucuronide. The metabolic pathway
of VAS in vivo and in vitro mainly involved monohydroxylation, dihydroxylation,
trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The
main metabolic soft spots in the chemical structure of VAS were the 3-hydroxyl
group and the C-9 site. All 72 metabolites were found in the urine sample, and
15, 25, 45, 18, and 11 metabolites were identified from rat feces, plasma, bile,
rat liver microsomes, and rat primary hepatocyte incubations, respectively.
Results indicated that renal clearance was the major excretion pathway of VAS.
The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory
activities of VAS and its main metabolites were also evaluated. The results
indicated that although most metabolites maintained potential inhibitory activity
against AChE and BChE, but weaker than that of VAS. VAS undergoes metabolic
inactivation process in vivo in respect to cholinesterase inhibitory activity.
PMID- 25849330
TI - FMS-like tyrosine kinase 3 ligand treatment does not ameliorate experimental
rapidly progressive glomerulonephritis.
AB - Fms-like tyrosine kinase 3-ligand (FL) is a growth factor that may expand
dendritic cell and regulatory T cell populations. We hypothesised that FL-induced
regulatory T cells would protect mice from experimental rapidly progressive
glomerulonephritis. To determine if FL was able to enhance regulatory T cell
populations, C57BL/6 mice received 10 days of daily intraperitoneal injections of
either FL or phosphate buffered saline. To induce accelerated autologous-phase
anti-mouse glomerular basement membrane glomerulonephritis, mice were sensitized
to sheep globulin 4 days prior to the induction of glomerulonephritis with sheep
anti-mouse glomerular basement membrane globulin, and experiments ended 10 days
later. FL was administered before, throughout and during the sensitization phase
of this glomerulonephritis model. Renal disease and systemic immunity to the
nephritogenic antigen were assessed. FL increased regulatory T cell and
plasmacytoid dendritic cell proportions within spleen and lymph nodes. FL
administration prior to glomerulonephritis did not protect mice from renal
injury. When FL was given throughout the model, FL treated mice had reduced
survival, with more interstitial neutrophils and glomerular CD11c+ cells than
controls. Systemic immune responses showed increased IL-17A production from
splenocytes, with more CD11c+ cells, but reduced plasmacytoid dendritic cell
proportions in spleen and lymph nodes, despite increased regulatory T cell
proportions. Under homeostatic conditions, FL expanded regulatory T cell and
plasmacytoid dendritic cell populations, but FL enhanced systemic inflammatory
responses and conventional dendritic cell populations when given during
experimental glomerulonephritis, suggesting selective attempts to suppress
pathogenic immunity by dendritic cell manipulation may be harmful.
PMID- 25849327
TI - Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be
associated with prognosis of estrogen receptor-negative breast cancer after
chemotherapy.
AB - INTRODUCTION: Tumor lymphocyte infiltration is associated with clinical response
to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify
variants in immunosuppressive pathway genes associated with prognosis after
adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive
breast cancer patients of European ancestry, including 9,334 ER-positive (3,151
treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with
chemotherapy). METHODS: We pooled data from sixteen studies from the Breast
Cancer Association Consortium (BCAC), and employed two independent studies for
replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes
were genotyped as part of the Collaborative Oncological Gene-environment Study,
in which phenotype and clinical data were collected and harmonized. Multivariable
Cox proportional hazard regression was used to assess genetic associations with
overall survival (OS) and breast cancer-specific survival (BCSS). Heterogeneity
according to chemotherapy or ER status was evaluated with the log-likelihood
ratio test. RESULTS: Three independent SNPs in TGFBR2 and IL12B were associated
with OS (P <10-3) solely in ER-negative patients after chemotherapy (267 events).
Poorer OS associated with TGFBR2 rs1367610 (G > C) (per allele hazard ratio (HR)
1.54 (95% confidence interval (CI) 1.22 to 1.95), P = 3.08 * 10-4) was not found
in ER-negative patients without chemotherapy or ER-positive patients with
chemotherapy (P for interaction <10-3). Two SNPs in IL12B (r2 = 0.20) showed
different associations with ER-negative disease after chemotherapy: rs2546892 (G
> A) with poorer OS (HR 1.50 (95% CI 1.21 to 1.86), P = 1.81 * 10-4), and
rs2853694 (A > C) with improved OS (HR 0.73 (95% CI 0.61 to 0.87), P = 3.67 * 10
4). Similar associations were observed with BCSS. Association with TGFBR2
rs1367610 but not IL12B variants replicated using BCAC Asian samples and the
independent Prospective Study of Outcomes in Sporadic versus Hereditary Breast
Cancer Study and yielded a combined HR of 1.57 ((95% CI 1.28 to 1.94), P = 2.05 *
10-5) without study heterogeneity. CONCLUSIONS: TGFBR2 variants may have
prognostic and predictive value in ER-negative breast cancer patients treated
with adjuvant chemotherapy. Our findings provide further insights into the
development of immunotherapeutic targets for ER-negative breast cancer.
PMID- 25849331
TI - Fibroblast-myofibroblast transition is differentially regulated by bronchial
epithelial cells from asthmatic children.
AB - BACKGROUND: Airway remodeling is a proposed mechanism that underlies the
persistent loss of lung function associated with childhood asthma. Previous
studies have demonstrated that human lung fibroblasts (HLFs) co-cultured with
primary human bronchial epithelial cells (BECs) from asthmatic children exhibit
greater expression of extracellular matrix (ECM) components compared to co
culture with BECs derived from healthy children. Myofibroblasts represent a
population of differentiated fibroblasts that have greater synthetic activity. We
hypothesized co-culture with asthmatic BECs would lead to greater fibroblast to
myofibroblast transition (FMT) compared to co-culture with healthy BECs. METHODS:
BECs were obtained from well-characterized asthmatic and healthy children and
were proliferated and differentiated at an air-liquid interface (ALI). BEC-ALI
cultures were co-cultured with HLFs for 96 hours. RT-PCR was performed in HLFs
for alpha smooth muscle actin (alpha-SMA) and flow cytometry was used to assay
for alpha-SMA antibody labeling of HLFs. RT-PCR was also preformed for the
expression of tropomyosin-I as an additional marker of myofibroblast phenotype.
In separate experiments, we investigated the role of TGFbeta2 in BEC-HLF co
cultures using monoclonal antibody inhibition. RESULTS: Expression of alpha-SMA
by HLFs alone was greater than by HLFs co-cultured with healthy BECs, but not
different than alpha-SMA expression by HLFs co-cultured with asthmatic BECs. Flow
cytometry also revealed significantly less alpha-SMA expression by healthy co-co
cultures compared to asthmatic co-cultures or HLF alone. Monoclonal antibody
inhibition of TGFbeta2 led to similar expression of alpha-SMA between healthy and
asthmatic BEC-HLF co-cultures. Expression of topomyosin-I was also significantly
increased in HLF co-cultured with asthmatic BECs compared to healthy BEC-HLF co
cultures or HLF cultured alone. CONCLUSION: These findings suggest dysregulation
of FMT in HLF co-cultured with asthmatic as compared to healthy BECs. Our results
suggest TGFbeta2 may be involved in the differential regulation of FMT by
asthmatic BECs. These findings further illustrate the importance of BEC-HLF cross
talk in asthmatic airway remodeling.
PMID- 25849332
TI - Use of the Blom Tracheotomy Tube with Suction Inner Cannula to Decontaminate
Microorganisms from the Subglottic Space. A Proof of Concept.
AB - RATIONALE: Preventing pulmonary complications during mechanical ventilation via
tracheotomy is a high priority. OBJECTIVES: To investigate if the Blom
tracheotomy tube with suction-above-the-cuff inner cannula reduced the quantity
of normal flora and pathogens in supra- versus subglottic spaces. METHODS: We
enrolled 20 consecutive medical ICU adults requiring tracheostomy for mechanical
ventilation in this proof-of-concept, prospective, single-center study. All
participants received a Blom tracheotomy tube with suction-above-the-cuff inner
cannula to decontaminate microorganisms from the supra- and subglottic spaces.
Supra- and subglottic sputum samples were obtained for microbiologic analysis
while an endotracheal tube was in place before tracheotomy and once per week for
up to 4 weeks of mechanical ventilation after tracheotomy. MEASUREMENTS AND MAIN
RESULTS: Demographics, duration of endotracheal tube intubation, and duration of
mechanical ventilation post-tracheotomy were recorded. There was a significant
reduction for supraglottic (2.86 +/- 1.11 [mean +/- SD]) versus subglottic
suction samples (2.48 +/- 1.07) (paired t test, P = 0.048; Wilcoxon test, P =
0.045) when all data pairs for normal flora and pathogens were combined across
times. There was a significant reduction of normal flora pooled across times in
19 data pairs for supraglottic (3.00 +/- 1.05) versus subglottic suction samples
(2.00 +/- 0.94) (paired t test, P = 0.0004; Wilcoxon test, P = 0.0007). There was
no significant reduction of pathogens pooled across times in 25 data pairs for
supraglottic (2.76 +/- 1.16) versus subglottic suction samples (2.84 +/- 1.03)
(paired t test, P = 0.75; Wilcoxon test, P = 0.83). CONCLUSIONS: Proof-of-concept
was confirmed. The Blom tracheotomy tube with disposable suction-above-the-cuff
inner cannula decontaminated microorganisms from the subglottic space when normal
flora and pathogens were combined. Future research should investigate if
decreased quantity of normal flora and pathogens in the subglottic space reduces
the incidence of ventilator-associated pulmonary complications in critically ill
patients requiring ongoing mechanical ventilation via tracheotomy.
PMID- 25849333
TI - An exploratory study on 99mTc-RGD-BBN peptide scintimammography in the assessment
of breast malignant lesions compared to 99mTc-3P4-RGD2.
AB - PURPOSE: This study aimed to explore the diagnostic performance of single photon
emission computed tomography / computerized tomography (SPECT/CT) using a new
radiotracer 99mTc-RGD-BBN for breast malignant tumor compared with 99mTc-3P4
RGD2. METHODS: 6 female patients with breast malignant tumors diagnosed by fine
needle aspiration cytology biopsy (FNAB) who were scheduled to undergo surgery
were included in the study. 99mTc-3P4-RGD2 and 99mTc-RGD-BBN were performed with
single photon emission computed tomography (SPECT) at 1 hour after intravenous
injection of 299 +/- 30 MBq and 293 +/- 32 MBq of radiotracers respectively at
separate day. The results were evaluated by the Tumor to non-Tumor ratios (T/NT).
99mTc-RGD-BBN and 99mTc-3P4-RGD2 SPECT/CT images were interpreted independently
by 3 experienced nuclear medicine physicians using a 3-point scale system. All of
the samples were analyzed immunohistochemically to evaluate the integrin
alphavbeta3 and gastrin-releasing peptide receptor (GRPR) expression. The safety,
biodistribution and radiation dosimetry of 99mTc-RGD-BBN were also evaluated in
the healthy volunteers. RESULTS: No serious adverse events were reported in any
of the patients during the study. The effective radiation dose entirely conformed
to the relevant standards. A total of 6 palpable malignant lesions were detected
using 99mTc-RGD-BBN SPECT/CT with clear uptake. All malignant lesions were also
detected using 99mTc-3P4-RGD2 SPECT/CT. The results showed that five malignant
lesions were with clear uptake and the other one with barely an uptake. 4
malignant cases were found with both alphavbeta3 and GRPR expression, 1 case with
only GRPR positive expression (integrin alphavbeta3 negative) and 1 case with
only integrin alphavbeta3 positive expression (GRPR negative). CONCLUSION: 99mTc
RGD-BBN is a safe agent for detecting breast cancer. 99mTc-RGD-BBN may have the
potential to make up for the deficiency of 99mTc-3P4-RGD2 in the detection of
breast cancer with only GRPR positive expression (integrin alphavbeta3 negative).
The preliminary application of 99mTc-RGD-BBN has demonstrated its powerful
potential in breast cancer diagnosis and therapy.
PMID- 25849334
TI - Genetic heterogeneity of the beta-globin gene in various geographic populations
of Yunnan in southwestern China.
AB - OBJECTIVES: The aim of this study was to investigate the geographic distribution
of beta-globin gene mutations in different ethnic groups in Yunnan province.
METHODS: From 2004 to 2014, 1,441 subjects with hemoglobin disorders, identified
by PCR-reverse dot blot and DNA sequencing, were studied according to ethnicity
and geographic origin. Haplotypes were examined among 41 unrelated thalassemia
chromosomes. RESULTS: Eighteen beta-thalassemia mutations and seven hemoglobin
variants were identified for 1,616 alleles in 22 different ethnic groups from all
16 prefecture-level divisions of Yunnan. The prevalence of beta-thalassemia was
heterogeneous and regionally specific. CD 41-42 (-TCTT) was the most prevalent
mutation in the populations of northeastern Yunnan. CD 17 (A>T) was the most
common mutation in the populations of southeastern Yunnan, especially for the
Zhuang minority, whereas Hb E (CD 26, G>A) was the most prevalent mutation in
populations of southwestern Yunnan, especially for the Dai minority. Among the
seven types of haplotypes identified, CD 17 (A>T) was mainly linked to haplotype
VII (+ - - - - - +) and IVS-II-654 (C>T) was only linked to haplotype I (+ - - -
+ +). CONCLUSION: Our data underline the heterogeneity of beta-globin gene
mutations in Yunnan. This distribution of beta-globin mutations in the geographic
regions and ethnic populations provided a detailed ethnic basis and evolutionary
view of humans in southern China, which will be beneficial for genetic counseling
and prevention strategies.
PMID- 25849335
TI - Tissue factor-expressing tumor cells can bind to immobilized recombinant tissue
factor pathway inhibitor under static and shear conditions in vitro.
AB - Mammary tumors and malignant breast cancer cell lines over-express the
coagulation factor, tissue factor (TF). High expression of TF is associated with
a poor prognosis in breast cancer. Tissue factor pathway inhibitor (TFPI), the
endogenous inhibitor of TF, is constitutively expressed on the endothelium. We
hypothesized that TF-expressing tumor cells can bind to immobilized recombinant
TFPI, leading to arrest of the tumor cells under shear in vitro. We evaluated the
adhesion of breast cancer cells to immobilized TFPI under static and shear
conditions (0.35 - 1.3 dyn/cm2). We found that high-TF-expressing breast cancer
cells, MDA-MB-231 (with a TF density of 460,000/cell), but not low TF-expressing
MCF-7 (with a TF density of 1,400/cell), adhered to recombinant TFPI, under
static and shear conditions. Adhesion of MDA-MB-231 cells to TFPI required
activated factor VII (FVIIa), but not FX, and was inhibited by a factor VIIa
blocking anti-TF antibody. Under shear, adhesion to TFPI was dependent on the
TFPI-coating concentration, FVIIa concentration and shear stress, with no
observed adhesion at shear stresses greater than 1.0 dyn/cm2. This is the first
study showing that TF-expressing tumor cells can be captured by immobilized TFPI,
a ligand constitutively expressed on the endothelium, under low shear in vitro.
Based on our results, we hypothesize that TFPI could be a novel ligand mediating
the arrest of TF-expressing tumor cells in high TFPI-expressing vessels under
conditions of low shear during metastasis.
PMID- 25849337
TI - Controlled motion of Janus particles in periodically phase-separating binary
fluids.
AB - We numerically investigate the propelled motions of a Janus particle in a
periodically phase-separating binary fluid mixture. In this study, the surface of
the particle tail prefers one of the binary fluid components and the particle
head is neutral in the wettability. During the demixing period, the more wettable
phase is selectively adsorbed to the particle tail. Growths of the adsorbed
domains induce the hydrodynamic flow in the vicinity of the particle tail, and
this asymmetric pumping flow drives the particle toward the particle head. During
the mixing period, the particle motion almost ceases because the mixing primarily
occurs via diffusion and the resulting hydrodynamic flow is negligibly small.
Repeating this cycle unboundedly moves the Janus particle toward the head. The
dependencies of the composition and the repeat frequency on the particle motion
are discussed.
PMID- 25849336
TI - RANK-ligand (RANKL) expression in young breast cancer patients and during
pregnancy.
AB - INTRODUCTION: RANKL is important in mammary gland development during pregnancy
and mediates the initiation and progression of progesterone-induced breast
cancer. No clinical data are available on the effect of pregnancy on RANK/RANKL
expression in young breast cancer patients. METHODS: We used our previously
published dataset of 65 pregnant and 130 matched young breast cancer patients
with full clinical, pathological, and survival information. 85% of patients had
available transcriptomic data as well. RANK/RANKL expression by
immunohistochemistry using H-score on the primary tumor and adjacent normal
tissue was performed. We examined the difference in expression of RANK/RANKL
between pregnant and non-pregnant patients and their association with
clinicopathological features and prognosis. We also evaluated genes and pathways
associated with RANK/RANKL expression on primary tumors. RESULTS: RANKL but not
RANK expression was more prevalent in the pregnant group, both on the tumor and
adjacent normal tissue, independent of other clinicopathological factors (both P
<0.001). 18.7% of pregnant and 5.3% of non-pregnant patients had tumors showing
>=10% of cells with 3+ RANKL expression. RANKL expression was significantly
higher in progesterone receptor-positive, and luminal A-like tumors, with
negative correlation with Ki-67 (all P <0.001). On the contrary, RANK expression
was higher in triple negative tumors (P <0.001). Using false discovery rate
<0.05, 151 and 1,207 genes were significantly correlated with tumor-expressed
RANKL and RANK expression by immunohistochemistry, respectively. High RANKL
expression within primary tumor was associated with pathways related to mammary
gland development, bone resorption, T-cell proliferation and regulation of
chemotaxis, while RANK expression was associated with immune response and
proliferation pathways. At a median follow-up of 65 months, neither RANK nor
RANKL expression within tumor was associated with disease free survival in
pregnant or non-pregnant group. CONCLUSIONS: Pregnancy increases RANKL expression
both in normal breast and primary tumors. These results could guide further
development of RANKL-targeted therapy.
PMID- 25849339
TI - Supernumerary horseshoe kidneys.
PMID- 25849338
TI - Liver-to-plasma vaniprevir (MK-7009) concentration ratios in HCV-infected
patients.
AB - BACKGROUND: Some drugs that are actively taken up into the liver exhibit greater
than dose proportional increases in plasma exposure, although human liver-to
plasma concentration ratios have rarely been evaluated. Understanding these
relationships has implications for drug concentrations at the target site for
certain classes of compounds, such as direct-acting antivirals, targeted towards
HCV. METHODS: Treatment-experienced, chronic HCV non-cirrhotic patients (n=3)
received vaniprevir (600 mg or 300 mg twice daily) on days 1-3 and (600 mg or 300
mg single dose) on day 4. Core needle biopsy was performed at 6 or 12 h post-dose
on day 4. Blood samples were collected pre-dose on days 1 and 4, and for 24 h
post-dose on day 4. The primary study objective was the hepatic concentration of
vaniprevir at 6 and 12 h post-dose. RESULTS: Vaniprevir plasma pharmacokinetic
parameters increased in a greater than dose-proportional manner between the 300
mg and 600 mg doses, with approximately fivefold increases in AUC0-12 and Cmax
associated with a twofold increase in dose (AUC0-12, 10.6 MUM/h to 59.5 MUM/h;
Cmax, 2.60 MUM to 13.5 MUM). In the 300 mg and 600 mg dose groups, mean liver
concentrations of vaniprevir were 84.6 MUM and 169 MUM at 6 h post-dose, and 29.4
MUM and 53.7 MUM at 12 h post-dose. Liver concentrations were higher than plasma
with liver-to-plasma concentration ratios of approximately 20-280. CONCLUSIONS:
These data confirm higher vaniprevir concentrations in human liver compared with
plasma and demonstrate that measurement of human liver drug concentration using
needle biopsy is feasible.
PMID- 25849340
TI - Ictal depth EEG and MRI structural evidence for two different epileptogenic
networks in mesial temporal lobe epilepsy.
AB - Hypersynchronous (HYP) and low voltage fast (LVF) activity are two separate ictal
depth EEG onsets patterns often recorded in presurgical patients with MTLE.
Evidence suggests the mechanisms generating HYP and LVF onset seizures are
distinct, including differential involvement of hippocampal and extra-hippocampal
sites. Yet the extent of extra-hippocampal structural alterations, which could
support these two common seizures, is not known. In the current study,
preoperative MRI from 24 patients with HYP or LVF onset seizures were analyzed to
determine changes in cortical thickness and relate structural changes to
spatiotemporal properties of the ictal EEG. Overall, onset and initial
ipsilateral spread of HYP onset seizures involved mesial temporal structures,
whereas LVF onset seizures involved mesial and lateral temporal as well as
orbitofrontal cortex. MRI analysis found reduced cortical thickness correlated
with longer duration of epilepsy. However, in patients with HYP onsets, the most
affected areas were on the medial surface of each hemisphere, including
parahippocampal regions and cingulate gyrus, whereas in patients with LVF onsets,
the lateral surface of the anterior temporal lobe and orbitofrontal cortex showed
the greatest effect. Most patients with HYP onset seizures were seizure-free
after resective surgery, while a higher proportion of patients with LVF onset
seizures had only worthwhile improvement. Our findings confirm the view that
recurrent seizures cause progressive changes in cortical thickness, and provide
information concerning the structural basis of two different epileptogenic
networks responsible for MTLE. One, identified by HYP ictal onsets, chiefly
involves hippocampus and is associated with excellent outcome after standardized
anteromedial temporal resection, while the other also involves lateral temporal
and orbitofrontal cortex and a seizure-free surgical outcome occurs less after
this procedure. These results suggest that a more extensive tailored resection
may be required for patients with the second type of MTLE.
PMID- 25849341
TI - The anti-diabetic effects of GLP-1-gastrin dual agonist ZP3022 in ZDF rats.
AB - AIMS/HYPOTHESIS: Combination treatment with exendin-4 and gastrin has proven
beneficial in treatment of diabetes and preservation of beta cell mass in
diabetic mice. Here, we examined the chronic effects of a GLP-1-gastrin dual
agonist ZP3022 on glycemic control and beta cell dysfunction in overtly diabetic
Zucker Diabetic Fatty (ZDF) rats. METHODS: ZDF rats aged 11 weeks were dosed
s.c., b.i.d. for 8 weeks with vehicle, ZP3022, liraglutide, exendin-4, or gastrin
17 with or without exendin-4. Glycemic control was assessed by measurements of
HbA1c and blood glucose levels, as well as glucose tolerance during an oral
glucose tolerance test (OGTT). Beta cell dynamics were examined by morphometric
analyses of beta and alpha cell fractions. RESULTS: ZP3022 improved glycemic
control as measured by terminal HbA1c levels (6.2+/-0.12 (high dose) vs. 7.9+/
0.07% (vehicle), P<0.001), as did all treatments, except gastrin-17 monotherapy.
In contrast, only ZP3022, exendin-4 and combination treatment with exendin-4 and
gastrin-17 significantly improved glucose tolerance and increased insulin levels
during an OGTT. Moreover, only ZP3022 significantly enhanced the beta cell
fraction in ZDF rats, a difference of 41%, when compared to the vehicle group
(0.31+/-0.03 vs. 0.22+/-0.02%, respectively, P<0.05). CONCLUSION: These data
suggest that ZP3022 may have therapeutic potential in the prevention/delay of
beta cell dysfunction in type 2 diabetes.
PMID- 25849342
TI - Prediction of all-cause mortality with copeptin in cardio-cerebrovascular
patients: A meta-analysis of prospective studies.
AB - BACKGROUND: Measurement of the biomarker copeptin may help identify disease
severity and risk of mortality for a various diseases. This study sought to
determine the relationship between copeptin and all-cause mortality of patients
with cardio-cerebrovascular disease. METHODS: Database of Medline and Web of
Science were searched for studies with data involving the baseline copeptin
levels and subsequent all-cause mortality outcomes. The pooled HRs of all-cause
mortality were calculated and presented with 95%CIs. Subgroup analysis and
sensitivity analysis were conducted to explore the possible sources of
heterogeneity. RESULTS: Data from 14,395 participants were derived from 28
prospective studies. Higher copeptin significantly increased the risk of all
cause mortality (per unit copeptin: HR=1.020, 95%CI=1.004-1.036; log unit
copeptin: HR=2.884, 95%CI=1.844-4.512; categorical copeptin: HR=3.371,
95%CI=2.077-5.472). Subgroup analysis indicated that the risk of all-cause death
was higher in cerebrovascular patients (per unit copeptin: HR=2.537, 95%CI=0.956
6.731; log unit copeptin: HR=3.419, 95%CI=2.391-4.888) than cardiovascular
patients (per unit copeptin: HR=1.011, 95%CI=1.002-1.020; log unit copeptin:
HR=2.009, 95%CI=1.119-3.608). CONCLUSION: Copeptin is associated with all-cause
mortality of patients with cardiovascular and cerebrovascular disease. Our study
suggests that copeptin seems to be a promising novel biomarker for prediction of
mortality in cardio-cerebrovascular patients, especially for cerebrovascular
patients.
PMID- 25849343
TI - Host-defense and trefoil factor family peptides in skin secretions of the Mawa
clawed frog Xenopus boumbaensis (Pipidae).
AB - Peptidomic analysis of norepinephrine-stimulated skin secretions from the
octoploid Mawa clawed frog Xenopus boumbaensis Loumont, 1983 led to the
identification and characterization of 15 host-defense peptides belonging to the
magainin (two peptides), peptide glycine-leucine-amide (PGLa; three peptides),
xenopsin precursor fragment (XPF; three peptides), caerulein precursor fragment
(CPF; two peptides), and caerulein precursor fragment-related peptide (CPF-RP;
five peptides) families. In addition, caerulein and three peptides with
structural similarity to the trefoil factor family (TFF) peptides, xP2 and xP4
from Xenopus laevis were also present in the secretions. Consistent with data
from comparisons of the nucleotides sequence of mitochondrial and nuclear genes,
the primary structures of the peptides suggest a close phylogenetic relationship
between X. boumbaensis and the octoploid frogs Xenopus amieti and Xenopus andrei.
As the three species occupy disjunct ranges within Cameroon, it is suggested that
they diverged from a common ancestor by allopatric speciation.
PMID- 25849344
TI - Influences on influenza transmission within terminal based on hierarchical
structure of personal contact network.
AB - BACKGROUND: Since the outbreak of pandemics, influenza has caused extensive
attention in the field of public health. It is actually hard to distinguish what
is the most effective method to control the influenza transmission within airport
terminal. The purpose of this study was to quantitatively evaluate the influences
of passenger source, immunity difference and social relation structure on the
influenza transmission in terminal. METHODS: A method combining hierarchical
structure of personal contact network with agent-based SEIR model was proposed to
analyze the characteristics of influenza diffusion within terminal. Based on the
spatial distance between individuals, the hierarchical structure of personal
contact network was defined to construct a complex relationship of passengers in
the real world. Moreover, the agent-based SEIR model was improved by considering
the individual level of influenza spread characteristics. To evaluate the method,
this process was fused in simulation based on the constructed personal contact
network. RESULTS: In the terminal we investigated, personal contact network was
defined by following four layers: social relation structure, procedure partition,
procedure area, and the whole terminal. With the growing of layer, the degree
distribution curves move right. The value of degree distribution p(k) reached a
peak at a specific value, and then back down. Besides, with the increase of layer
alpha, the clustering coefficients presented a tendency to exponential decay.
Based on the influenza transmission experiments, the main infected areas were
concluded when considering different factors. Moreover, partition of passenger
sources was found to impact a lot in departure, while social relation structure
imposed a great influence in arrival. Besides, immunity difference exerted no
obvious effect on the spread of influenza in the transmission process both in
departure and arrival. CONCLUSIONS: The proposed method is efficient to reproduce
the evolution process of influenza transmission, and exhibits various roles of
each factor in different processes, also better reflects the effect of passenger
topological character on influenza spread. It contributes to proposing effective
influenza measures by airport relevant department and improving the efficiency
and ability of epidemic prevention on the public health.
PMID- 25849345
TI - Direct evaluation of molecular States of piroxicam/poloxamer nanosuspension by
suspended-state NMR and Raman spectroscopies.
AB - A nanosuspension of piroxicam (PXC) and poloxamer 407 (poloxamer) prepared by the
wet milling method was directly evaluated at the molecular level from the
viewpoint of both solution and solid phases. (13)C solution-state NMR
measurements revealed a reduction in the concentration of dissolved poloxamer in
the nanosuspension. Furthermore, the fraction of dissolved poly(ethylene oxide)
(PEO) chain, which is the hydrophilic part of poloxamer, was higher than that of
dissolved poly(propylene oxide) (PPO) chain, the hydrophobic part. (13)C
suspended-state NMR and Raman spectroscopies detected both solid-state PXC and
poloxamer involved in the nanoparticles. Interestingly, the coexistence of
crystalline and amorphous PXC in the nanoparticle was demonstrated. The yellow
color of the nanosuspension strongly supported the existence of amorphous PXC.
Changes in the peak intensity depending on the contact time in the suspended
state NMR spectrum revealed that the PEO chain of poloxamer in the nanoparticle
had higher mobility compared with the PPO chain. The PEO chain should project
into the water phase and form the outer layer of the nanoparticles, whereas the
PPO chain should face the inner side of the nanoparticles. Amorphous PXC could be
stabilized by intermolecular interaction with the PPO chain near the surface of
the nanoparticles, whereas crystalline PXC could form the inner core.
PMID- 25849347
TI - The Scanning TMR Microscope for Biosensor Applications.
AB - We present a novel tunnel magnetoresistance (TMR) scanning microscope set-up
capable of quantitatively imaging the magnetic stray field patterns of micron
sized elements in 3D. By incorporating an Anderson loop measurement circuit for
impedance matching, we are able to detect magnetoresistance changes of as little
as 0.006%/Oe. By 3D rastering a mounted TMR sensor over our magnetic barcodes, we
are able to characterize the complex domain structures by displaying the real
component, the amplitude and the phase of the sensor's impedance. The modular
design, incorporating a TMR sensor with an optical microscope, renders this set
up a versatile platform for studying and imaging immobilised magnetic carriers
and barcodes currently employed in biosensor platforms, magnetotactic bacteria
and other complex magnetic domain structures of micron-sized entities. The
quantitative nature of the instrument and its ability to produce vector maps of
magnetic stray fields has the potential to provide significant advantages over
other commonly used scanning magnetometry techniques.
PMID- 25849346
TI - Plasma membrane mechanical stress activates TRPC5 channels.
AB - Mechanical forces exerted on cells impose stress on the plasma membrane. Cells
sense this stress and elicit a mechanoelectric transduction cascade that
initiates compensatory mechanisms. Mechanosensitive ion channels in the plasma
membrane are responsible for transducing the mechanical signals to electrical
signals. However, the mechanisms underlying channel activation in response to
mechanical stress remain incompletely understood. Transient Receptor Potential
(TRP) channels serve essential functions in several sensory modalities. These
channels can also participate in mechanotransduction by either being autonomously
sensitive to mechanical perturbation or by coupling to other mechanosensory
components of the cell. Here, we investigated the response of a TRP family
member, TRPC5, to mechanical stress. Hypoosmolarity triggers Ca2+ influx and
cationic conductance through TRPC5. Importantly, for the first time we were able
to record the stretch-activated TRPC5 current at single-channel level. The
activation threshold for TRPC5 was found to be 240 mOsm for hypoosmotic stress
and between -20 and -40 mmHg for pressure applied to membrane patch. In addition,
we found that disruption of actin filaments suppresses TRPC5 response to
hypoosmotic stress and patch pipette pressure, but does not prevent the
activation of TRPC5 by stretch-independent mechanisms, indicating that actin
cytoskeleton is an essential transduction component that confers
mechanosensitivity to TRPC5. In summary, our findings establish that TRPC5 can be
activated at the single-channel level when mechanical stress on the cell reaches
a certain threshold.
PMID- 25849348
TI - The impact of the carer support needs assessment tool (CSNAT) in community
palliative care using a stepped wedge cluster trial.
AB - Family caregiving towards the end-of-life entails considerable emotional, social,
financial and physical costs for caregivers. Evidence suggests that good support
can improve caregiver psychological outcomes. The primary aim of this study was
to investigate the impact of using the carer support needs assessment tool
(CSNAT), as an intervention to identify and address support needs in end of life
home care, on family caregiver outcomes. A stepped wedge design was used to trial
the CSNAT intervention in three bases of Silver Chain Hospice Care in Western
Australia, 2012-14. The intervention consisted of at least two visits from nurses
(2-3 weeks apart) to identify, review and address caregivers' needs. The outcome
measures for the intervention and control groups were caregiver strain and
distress as measured by the Family Appraisal of Caregiving Questionnaire (FACQ
PC), caregiver mental and physical health as measured by SF-12v2, and caregiver
workload as measured by extent of caregiver assistance with activities of daily
living, at baseline and follow up. Total recruitment was 620. There was 45%
attrition for each group between baseline and follow-up mainly due to patient
deaths resulting in 322 caregivers completing the study (233 in the intervention
group and 89 in the control group). At follow-up, the intervention group showed
significant reduction in caregiver strain relative to controls, p=0.018, d=0.348
(95% CI 0.25 to 0.41). Priority support needs identified by caregivers included
knowing what to expect in the future, having time for yourself in the day and
dealing with your feelings and worries. Despite the challenges at the clinician,
organisational and trial levels, the CSNAT intervention led to an improvement in
caregiver strain. Effective implementation of an evidence-informed and caregiver
led tool represents a necessary step towards helping palliative care providers
better assess and address caregiver needs, ensuring adequate family caregiver
support and reduction in caregiver strain.
PMID- 25849349
TI - Embodied choice: how action influences perceptual decision making.
AB - Embodied Choice considers action performance as a proper part of the decision
making process rather than merely as a means to report the decision. The central
statement of embodied choice is the existence of bidirectional influences between
action and decisions. This implies that for a decision expressed by an action,
the action dynamics and its constraints (e.g. current trajectory and kinematics)
influence the decision making process. Here we use a perceptual decision making
task to compare three types of model: a serial decision-then-action model, a
parallel decision-and-action model, and an embodied choice model where the action
feeds back into the decision making. The embodied model incorporates two key
mechanisms that together are lacking in the other models: action preparation and
commitment. First, action preparation strategies alleviate delays in enacting a
choice but also modify decision termination. Second, action dynamics change the
prospects and create a commitment effect to the initially preferred choice. Our
results show that these two mechanisms make embodied choice models better suited
to combine decision and action appropriately to achieve suitably fast and
accurate responses, as usually required in ecologically valid situations.
Moreover, embodied choice models with these mechanisms give a better account of
trajectory tracking experiments during decision making. In conclusion, the
embodied choice framework offers a combined theory of decision and action that
gives a clear case that embodied phenomena such as the dynamics of actions can
have a causal influence on central cognition.
PMID- 25849350
TI - Restoration of motion-blurred image based on border deformation detection: a
traffic sign restoration model.
AB - Due to the rapid development of motor vehicle Driver Assistance Systems (DAS),
the safety problems associated with automatic driving have become a hot issue in
Intelligent Transportation. The traffic sign is one of the most important tools
used to reinforce traffic rules. However, traffic sign image degradation based on
computer vision is unavoidable during the vehicle movement process. In order to
quickly and accurately recognize traffic signs in motion-blurred images in DAS, a
new image restoration algorithm based on border deformation detection in the
spatial domain is proposed in this paper. The border of a traffic sign is
extracted using color information, and then the width of the border is measured
in all directions. According to the width measured and the corresponding
direction, both the motion direction and scale of the image can be confirmed, and
this information can be used to restore the motion-blurred image. Finally, a gray
mean grads (GMG) ratio is presented to evaluate the image restoration quality.
Compared to the traditional restoration approach which is based on the blind
deconvolution method and Lucy-Richardson method, our method can greatly restore
motion blurred images and improve the correct recognition rate. Our experiments
show that the proposed method is able to restore traffic sign information
accurately and efficiently.
PMID- 25849351
TI - Dietary n-3 polyunsaturated fatty acid intakes modify the effect of genetic
variation in fatty acid desaturase 1 on coronary artery disease.
AB - BACKGROUND: Previous studies suggested that dietary fatty acids could affect
blood lipids by interacting with genetic variations in fatty acid desaturase 1
(FADS1). However, little is known about their direct effects on coronary artery
disease (CAD). The aim of this study was to evaluate whether dietary n-3 long
chain polyunsaturated fatty acids (LCPUFAs)-eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) could modulate the effect of FADS1 rs174547
polymorphism on CAD. METHODS: FADS1 single-nucleotide polymorphisms rs174547
genotypes were measured in 440 CAD patients and 838 healthy controls. Dietary EPA
and DHA intakes were assessed with a validated quantitative frequency food
questionnaire. The association between FADS1 rs174547 and CAD was estimated using
logistic regression under both dominant and additive genetic models. The
interactions between rs174547 polymorphism and LCPUFAs were analyzed by using
multiple logistic regression and the "genotype * n-3 LCPUFAs" interaction term
was included into the model. RESULTS: We found that the minor T allele of FADS1
rs174547 increased CAD risk (OR = 1.36, 95%CIs 1.03-1.80), and observed
significant interaction between rs174547 and dietary EPA intakes on CAD (P
interaction = 0.028). The T-allele was only associated with higher CAD risk among
individuals with lower dietary EPA intakes, but not in those with higher EPA
intakes. Similarly, significant interaction was also observed between rs174547
and dietary DHA intakes on CAD (P-interaction = 0.020). CONCLUSIONS: Dietary n-3
LCPUFA intakes could modulate the association between FADS1 rs174547 polymorphism
and CAD. High dietary n-3 LCPUFA intakes could negate the unfavorable effect of
genetic variation in FADS1 on CAD in middle-aged and elderly Chinese population.
PMID- 25849353
TI - Correction: identification of modulators of the nuclear receptor peroxisome
proliferator-activated receptor alpha (PPARalpha) in a mouse liver gene
expression compendium.
PMID- 25849354
TI - Gonadotropin-releasing hormone agonist overuse: urologists' response to
reimbursement and characteristics associated with persistent overuse.
AB - BACKGROUND: Medicare reimbursement cuts have been associated with declining
gonadotropin-releasing hormone (GnRH) agonist overuse in localized prostate
cancer. Medical school affiliation and foreign training have been associated with
persistent overuse. However, physician-level prescribing changes and the practice
type of persistent overusers have not been examined. We sought to describe
physician-level changes in GnRH agonist overuse and test the association of time
in practice and solo practice type with GnRH agonist overuse. METHODS: We matched
American Medical Association physician data for 2138 urologists to Surveillance,
Epidemiology and End Result-Medicare data for 12,943 men diagnosed with early
stage and lower-grade adenocarcinoma of the prostate between 2000 and 2007. We
conducted a population-based, retrospective study using multilevel modeling to
control for patient and provider characteristics. RESULTS: Three distinct
patterns of GnRH agonist overuse were observed. Urologists' time in practice was
not associated with GnRH agonist overuse (odds ratio (OR) 0.89; 95% confidence
interval (CI): 0.75-1.05). However, solo practice type (OR 1.65; 95% CI: 1.34
2.02), medical school affiliation (OR 0.65; 95% CI: 0.55-0.77) and patient race
were. Compared with non-Hispanic whites, non-Hispanic blacks (OR 1.76; 95% CI:
1.37-2.27), Hispanics (OR 1.41; 95% CI: 1.12-1.79) and men of 'other' race (OR
1.44; 95% CI: 1.04-1.99) had greater odds of receiving unnecessary GnRH agonists.
CONCLUSIONS: GnRH agonist overuse remains high among some urologists who may be
professionally isolated and difficult to reach. These urologists treat more
vulnerable populations, which may contribute to health disparities in prostate
cancer treatment quality. Nonetheless, these findings provide guidance to develop
interventions to address overuse in prostate cancer.
PMID- 25849355
TI - Endocytosis as a biological response in receptor pharmacology: evaluation by
fluorescence microscopy.
AB - The activation of G-protein coupled receptors by agonist compounds results in
diverse biological responses in cells, such as the endocytosis process consisting
in the translocation of receptors from the plasma membrane to the cytoplasm
within internalizing vesicles or endosomes. In order to functionally evaluate
endocytosis events resulted from pharmacological responses, we have developed an
image analysis method -the Q-Endosomes algorithm- that specifically discriminates
the fluorescent signal originated at endosomes from that one observed at the
plasma membrane in images obtained from living cells by fluorescence microscopy.
Mu opioid (MOP) receptor tagged at the carboxy-terminus with yellow fluorescent
protein (YFP) and permanently expressed in HEK293 cells was used as experimental
model to validate this methodology. Time-course experiments performed with
several agonists resulted in different sigmoid curves depending on the drug used
to initiate MOP receptor endocytosis. Thus, endocytosis resulting from the
simultaneous activation of co-expressed MOP and serotonin 5-HT2C receptors by
morphine plus serotonin was significantly different, in kinetics as well as in
maximal response parameters, from the one caused by DAMGO, sufentanyl or
methadone. Therefore, this analytical tool permits the pharmacological
characterization of receptor endocytosis in living cells with functional and
temporal resolution.
PMID- 25849352
TI - Geographic and temporal trends in the molecular epidemiology and genetic
mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and
sequence-level meta-analysis.
AB - BACKGROUND: Regional and subtype-specific mutational patterns of HIV-1
transmitted drug resistance (TDR) are essential for informing first-line
antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use
in regions where standard genotypic resistance testing is not affordable. We
sought to understand the molecular epidemiology of TDR and to identify the HIV-1
drug-resistance mutations responsible for TDR in different regions and virus
subtypes. METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1
reverse transcriptase sequences with or without protease and identified 287
studies published between March 1, 2000, and December 31, 2013, with more than 25
recently or chronically infected ARV-naive individuals. These studies comprised
50,870 individuals from 111 countries. Each set of study sequences was analyzed
for phylogenetic clustering and the presence of 93 surveillance drug-resistance
mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA),
south/southeast Asia (SSEA), upper-income Asian countries, Latin
America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%,
and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14)
increase in odds of TDR since national ARV scale-up attributable to an increase
in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of
NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] =
1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe
(OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95%
CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since
national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to
sequences with mixtures at less than 0.5% of their nucleotide positions-a proxy
for recent infection-yielded trends comparable to those obtained using the
complete dataset. Four NNRTI SDRMs-K101E, K103N, Y181C, and G190A-accounted for
>80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside
reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI
associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs
were associated with high-level resistance to nevirapine or efavirenz, whereas
only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine,
lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725
(95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent
limitations of this study are that some cohorts may not represent the broader
regional population and that studies were heterogeneous with respect to duration
of infection prior to sampling. CONCLUSIONS: Most TDR strains in SSA and SSEA
arose independently, suggesting that ARV regimens with a high genetic barrier to
resistance combined with improved patient adherence may mitigate TDR increases by
reducing the generation of new ARV-resistant strains. A small number of NNRTI
resistance mutations were responsible for most cases of high-level resistance,
suggesting that inexpensive point-mutation assays to detect these mutations may
be useful for pre-therapy screening in regions with high levels of TDR. In the
context of a public health approach to ARV therapy, a reliable point-of-care
genotypic resistance test could identify which patients should receive standard
first-line therapy and which should receive a protease-inhibitor-containing
regimen.
PMID- 25849356
TI - Rural, urban and migrant differences in non-communicable disease risk-factors in
middle income countries: a cross-sectional study of WHO-SAGE data.
AB - BACKGROUND: Understanding how urbanisation and rural-urban migration influence
risk-factors for non-communicable disease (NCD) is crucial for developing
effective preventative strategies globally. This study compares NCD risk-factor
prevalence in urban, rural and migrant populations in China, Ghana, India,
Mexico, Russia and South Africa. METHODS: Study participants were 39,436 adults
within the WHO Study on global AGEing and adult health (SAGE), surveyed 2007
2010. Risk ratios (RR) for each risk-factor were calculated using logistic
regression in country-specific and all country pooled analyses, adjusted for age,
sex and survey design. Fully adjusted models included income quintile, marital
status and education. RESULTS: Regular alcohol consumption was lower in migrant
and urban groups than in rural groups (pooled RR and 95%CI: 0.47 (0.31-0.68);
0.58, (0.46-0.72), respectively). Occupational physical activity was lower (0.86
(0.72-0.98); 0.76 (0.65-0.85)) while active travel and recreational physical
activity were higher (pooled RRs for urban groups; 1.05 (1.00-1.09), 2.36 (1.95
2.83), respectively; for migrant groups: 1.07 (1.0 -1.12), 1.71 (1.11-2.53),
respectively). Overweight, raised waist circumference and diagnosed diabetes were
higher in urban groups (1.19 (1.04-1.35), 1.24 (1.07-1.42), 1.69 (1.15-2.47),
respectively). Exceptions to these trends exist: obesity indicators were higher
in rural Russia; active travel was lower in urban groups in Ghana and India; and
in South Africa, urban groups had the highest alcohol consumption. CONCLUSION:
Migrants and urban dwellers had similar NCD risk-factor profiles. These were not
consistently worse than those seen in rural dwellers. The variable impact of
urbanisation on NCD risk must be considered in the design and evaluation of
strategies to reduce the growing burden of NCDs globally.
PMID- 25849357
TI - Pulse and entrainment to non-isochronous auditory stimuli: the case of north
Indian alap.
AB - Pulse is often understood as a feature of a (quasi-) isochronous event sequence
that is picked up by an entrained subject. However, entrainment does not only
occur between quasi-periodic rhythms. This paper demonstrates the expression of
pulse by subjects listening to non-periodic musical stimuli and investigates the
processes behind this behaviour. The stimuli are extracts from the introductory
sections of North Indian (Hindustani) classical music performances (alap, jor and
jhala). The first of three experiments demonstrates regular motor responses to
both irregular alap and more regular jor sections: responses to alap appear
related to individual spontaneous tempi, while for jor they relate to the
stimulus event rate. A second experiment investigated whether subjects respond to
average periodicities of the alap section, and whether their responses show phase
alignment to the musical events. In the third experiment we investigated
responses to a broader sample of performances, testing their relationship to
spontaneous tempo, and the effect of prior experience with this music. Our
results suggest an entrainment model in which pulse is understood as the
experience of one's internal periodicity: it is not necessarily linked to
temporally regular, structured sensory input streams; it can arise spontaneously
through the performance of repetitive motor actions, or on exposure to event
sequences with rather irregular temporal structures. Greater regularity in the
external event sequence leads to entrainment between motor responses and stimulus
sequence, modifying subjects' internal periodicities in such a way that they are
either identical or harmonically related to each other. This can be considered as
the basis for shared (rhythmic) experience and may be an important process
supporting 'social' effects of temporally regular music.
PMID- 25849359
TI - Efficient and anonymous two-factor user authentication in wireless sensor
networks: achieving user anonymity with lightweight sensor computation.
AB - A smart-card-based user authentication scheme for wireless sensor networks
(hereafter referred to as a SCA-WSN scheme) is designed to ensure that only users
who possess both a smart card and the corresponding password are allowed to gain
access to sensor data and their transmissions. Despite many research efforts in
recent years, it remains a challenging task to design an efficient SCA-WSN scheme
that achieves user anonymity. The majority of published SCA-WSN schemes use only
lightweight cryptographic techniques (rather than public-key cryptographic
techniques) for the sake of efficiency, and have been demonstrated to suffer from
the inability to provide user anonymity. Some schemes employ elliptic curve
cryptography for better security but require sensors with strict resource
constraints to perform computationally expensive scalar-point multiplications;
despite the increased computational requirements, these schemes do not provide
user anonymity. In this paper, we present a new SCA-WSN scheme that not only
achieves user anonymity but also is efficient in terms of the computation loads
for sensors. Our scheme employs elliptic curve cryptography but restricts its use
only to anonymous user-to-gateway authentication, thereby allowing sensors to
perform only lightweight cryptographic operations. Our scheme also enjoys
provable security in a formal model extended from the widely accepted Bellare
Pointcheval-Rogaway (2000) model to capture the user anonymity property and
various SCA-WSN specific attacks (e.g., stolen smart card attacks, node capture
attacks, privileged insider attacks, and stolen verifier attacks).
PMID- 25849358
TI - Longitudinal neurostimulation in older adults improves working memory.
AB - An increasing concern affecting a growing aging population is working memory (WM)
decline. Consequently, there is great interest in improving or stabilizing WM,
which drives expanded use of brain training exercises. Such regimens generally
result in temporary WM benefits to the trained tasks but minimal transfer of
benefit to untrained tasks. Pairing training with neurostimulation may stabilize
or improve WM performance by enhancing plasticity and strengthening WM-related
cortical networks. We tested this possibility in healthy older adults.
Participants received 10 sessions of sham (control) or active (anodal, 1.5 mA)
tDCS to the right prefrontal, parietal, or prefrontal/parietal (alternating)
cortices. After ten minutes of sham or active tDCS, participants performed verbal
and visual WM training tasks. On the first, tenth, and follow-up sessions,
participants performed transfer WM tasks including the spatial 2-back, Stroop,
and digit span tasks. The results demonstrated that all groups benefited from WM
training, as expected. However, at follow-up 1-month after training ended, only
the participants in the active tDCS groups maintained significant improvement.
Importantly, this pattern was observed for both trained and transfer tasks. These
results demonstrate that tDCS-linked WM training can provide long-term benefits
in maintaining cognitive training benefits and extending them to untrained tasks.
PMID- 25849360
TI - Unraveling the conformational landscape of triallyl phosphate: matrix isolation
infrared spectroscopy and density functional theory computations.
AB - The conformations of triallyl phosphate (TAP) were studied using matrix isolation
infrared spectroscopy and density functional theory (DFT) calculations. TAP was
trapped in N2, Ar, and Xe matrixes at 12 K using an effusive source and the
resultant infrared spectra recorded. The computational analysis on conformers of
TAP is a challenging problem due to the presence of the large number of
conformations. To simplify this problem, conformational analysis was performed on
prototypical molecules such as dimethyl allyl phosphate (DMAP) and diallyl methyl
phosphate (DAMP), to systematically arrive at the conformations of TAP. The above
methodology discerned 131 conformations for TAP, which were found to contribute
to the room temperature population. The computations were performed using B3LYP/6
311++G(d,p) level of theory. Vibrational wavenumber calculations were performed
for the various conformers to assign the experimental infrared features of TAP,
trapped in solid N2, Ar, and Xe matrixes.
PMID- 25849361
TI - Presence, objecthood, and the phenomenology of predictive perception.
AB - Can perceptual presence be explained by counterfactually-rich predictive models
linking perception and action? Considering an unusually rich range of responses
to this idea has led me to (1) re-emphasize the core conceptual commitment of
"predictive processing of sensorimotor contingencies" (PPSMC) to predictive model
based perception, (2) reconsider the relationship between presence and
objecthood, and (3) refine the phenomenological target by differentiating between
perceptual presence and the phenomenology of absence-of-presence, or "phenomenal
unreality." It turns out that this requires blue-sky thinking.
PMID- 25849362
TI - Compound heterozygous mutation of Rag1 leading to Omenn syndrome.
AB - Omenn syndrome is a primary immunodeficiency disorder, featuring susceptibility
to infections and autoreactive T cells and resulting from defective genomic
rearrangement of genes for the T cell and B cell receptors. The most frequent
etiologies are hypomorphic mutations in "non-core" regions of the Rag1 or Rag2
genes, the protein products of which are critical members of the cellular
apparatus for V(D)J recombination. In this report, we describe an infant with
Omenn syndrome with a previously unreported termination mutation (p.R142*) in
Rag1 on one allele and a partially characterized substitution mutation (p.V779M)
in a "core" region of the other Rag1 allele. Using a cellular recombination
assay, we found that while the p.R142* mutation completely abolished V(D)J
recombination activity, the p.V779M mutation conferred a severe, but not total,
loss of V(D)J recombination activity. The recombination defect of the V779 mutant
was not due to overall misfolding of Rag1, however, as this mutant supported wild
type levels of V(D)J cleavage. These findings provide insight into the role of
this poorly understood region of Rag1 and support the role of Rag1 in a post
cleavage stage of recombination.
PMID- 25849363
TI - The interaction of Arabidopsis with Piriformospora indica shifts from initial
transient stress induced by fungus-released chemical mediators to a mutualistic
interaction after physical contact of the two symbionts.
AB - BACKGROUND: Piriformospora indica, an endophytic fungus of Sebacinales, colonizes
the roots of many plant species including Arabidopsis thaliana. The symbiotic
interaction promotes plant performance, growth and resistance/tolerance against
abiotic and biotic stress. RESULTS: We demonstrate that exudated compounds from
the fungus activate stress and defense responses in the Arabidopsis roots and
shoots before the two partners are in physical contact. They induce stomata
closure, stimulate reactive oxygen species (ROS) production, stress-related
phytohormone accumulation and activate defense and stress genes in the roots
and/or shoots. Once a physical contact is established, the stomata re-open, ROS
and phytohormone levels decline, and the number and expression level of
defense/stress-related genes decreases. CONCLUSIONS: We propose that exudated
compounds from P. indica induce stress and defense responses in the host. Root
colonization results in the down-regulation of defense responses and the
activation of genes involved in promoting plant growth, metabolism and
performance.
PMID- 25849364
TI - The association between chronic kidney disease and diabetic retinopathy: the
Korea National Health and Nutrition Examination Survey 2008-2010.
AB - PURPOSE: To explore the relationship between chronic kidney disease and diabetic
retinopathy in a representative population of Korean diabetic adults. METHODS: We
analyzed data from the Korea National Health and Nutrition Examination Surveys
(2008-2010). A total of 15,409 individuals (weighted frequency, 32,168,636) aged
19 and over who completed ophthalmologic and renal functional examinations were
evaluated. Chronic kidney disease (CKD) was defined as an estimated glomerular
filtration rate of < 60 ml/min/1.73 m2 or proteinuria greater than 1+. Seven
standard photographs from the Early Treatment for Diabetic Retinopathy Study were
obtained from each eye after pharmacological pupil dilatation. Diabetic
retinopathy (DR) was defined as the presence of 1 or more retinal microaneurysms
or retinal blot hemorrhages with or without more severe lesions. Vision
threatening diabetic retinopathy (VTDR) was defined as the presence of a
clinically significant macular edema (CSME) or proliferative diabetic
retinopathy. RESULTS: CKD was significantly associated with DR and VTDR (odds
ratio (OR), 95% confidence interval (CI); 2.49(1.43-4.35) and 3.74(1.56-8.95),
respectively) in the diabetic population. After controlling for confounders,
however, CKD was significantly associated only with DR [adjusted OR (aOR), 95%
CI; 2.34(1.04-5.28)]. In the subgroup analysis for CKD, only proteinuria was
significantly associated with DR and VTDR (aOR, 95% CI; 4.56(1.51-13.77) and
5.61(1.06-29.87), respectively) in this population. CONCLUSIONS: Our results show
that CKD appears to be associated with DR and VTDR in a Korean diabetic
population. In particular, proteinuria, not decreased eGFR, is more significantly
associated with DR or VTDR.
PMID- 25849365
TI - Cofactor specificity motifs and the induced fit mechanism in class I ketol-acid
reductoisomerases.
AB - Although most sequenced members of the industrially important ketol-acid
reductoisomerase (KARI) family are class I enzymes, structural studies to date
have focused primarily on the class II KARIs, which arose through domain
duplication. In the present study, we present five new crystal structures of
class I KARIs. These include the first structure of a KARI with a six-residue
beta2alphaB (cofactor specificity determining) loop and an NADPH phosphate
binding geometry distinct from that of the seven- and 12-residue loops. We also
present the first structures of naturally occurring KARIs that utilize NADH as
cofactor. These results show insertions in the specificity loops that confounded
previous attempts to classify them according to loop length. Lastly, we explore
the conformational changes that occur in class I KARIs upon binding of cofactor
and metal ions. The class I KARI structures indicate that the active sites close
upon binding NAD(P)H, similar to what is observed in the class II KARIs of rice
and spinach and different from the opening of the active site observed in the
class II KARI of Escherichia coli. This conformational change involves a decrease
in the bending of the helix that runs between the domains and a rearrangement of
the nicotinamide-binding site.
PMID- 25849366
TI - Mechanism of action studies of lomaiviticin A and the monomeric lomaiviticin
aglycon. Selective and potent activity toward DNA double-strand break repair
deficient cell lines.
AB - (-)-Lomaiviticin A (1) and the monomeric lomaiviticin aglycon [aka: (-)-MK7-206,
(3)] are cytotoxic agents that induce double-strand breaks (DSBs) in DNA. Here we
elucidate the cellular responses to these agents and identify synthetic lethal
interactions with specific DNA repair factors. Toward this end, we first
characterized the kinetics of DNA damage by 1 and 3 in human chronic myelogenous
leukemia (K562) cells. DSBs are rapidly induced by 3, reaching a maximum at 15
min post addition and are resolved within 4 h. By comparison, DSB production by 1
requires 2-4 h to achieve maximal values and >8 h to achieve resolution. As
evidenced by an alkaline comet unwinding assay, 3 induces extensive DNA damage,
suggesting that the observed DSBs arise from closely spaced single-strand breaks
(SSBs). Both 1 and 3 induce ataxia telangiectasia mutated- (ATM-) and DNA
dependent protein kinase- (DNA-PK-) dependent production of phospho-SER139
histone H2AX (gammaH2AX) and generation of p53 binding protein 1 (53BP1) foci in
K562 cells within 1 h of exposure, which is indicative of activation of
nonhomologous end joining (NHEJ) and homologous recombination (HR) repair. Both
compounds also lead to ataxia telangiectasia and Rad3-related- (ATR-) dependent
production of gammaH2AX at later time points (6 h post addition), which is
indicative of replication stress. 3 is also shown to induce apoptosis. In accord
with these data, 1 and 3 were found to be synthetic lethal with certain mutations
in DNA DSB repair. 1 potently inhibits the growth of breast cancer type 2, early
onset- (BRCA2-) deficient V79 Chinese hamster lung fibroblast cell line
derivative (VC8), and phosphatase and tensin homologue deleted on chromosome ten-
(PTEN-) deficient human glioblastoma (U251) cell lines, with LC50 values of 1.5
+/- 0.5 and 2.0 +/- 0.6 pM, respectively, and selectivities of >11.6 versus the
isogenic cell lines transfected with and expressing functional BRCA2 and PTEN
genes. 3 inhibits the growth of the same cell lines with LC50 values of 6.0 +/-
0.5 and 11 +/- 4 nM and selectivities of 84 and 5.1, for the BRCA2 and PTEN
mutants, respectively. These data argue for the evaluation of these agents as
treatments for tumors that are deficient in BRCA2 and PTEN, among other DSB
repair factors.
PMID- 25849368
TI - Single-layer ionic conduction on carboxyl-terminated silane monolayers patterned
by constructive lithography.
AB - Ionic transport plays a central role in key technologies relevant to energy, and
information processing and storage, as well as in the implementation of
biological functions in living organisms. Here, we introduce a supramolecular
strategy based on the non-destructive chemical patterning of a highly ordered
self-assembled monolayer that allows the reproducible fabrication of ion
conducting surface patterns (ion-conducting channels) with top -COOH functional
groups precisely definable over the full range of length scales from nanometre to
centimetre. The transport of a single layer of selected metal ions and the
electrochemical processes related to their motion may thus be confined to
predefined surface paths. As a generic solid ionic conductor that can accommodate
different mobile ions in the absence of any added electrolyte, these ion
conducting channels exhibit bias-induced competitive transport of different ionic
species. This approach offers unprecedented opportunities for the realization of
designed ion-conducting systems with nanoscale control, beyond the inherent
limitations posed by available ionic materials.
PMID- 25849367
TI - Effects of the I559P gp41 change on the conformation and function of the human
immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer.
AB - The mature human immunodeficiency virus (HIV-1) envelope glycoprotein (Env)
trimer is produced by proteolytic cleavage of a precursor and consists of three
gp120 exterior and three gp41 transmembrane subunits. The metastable Env complex
is induced to undergo conformational changes required for virus entry by the
binding of gp120 to the receptors, CD4 and CCR5/CXCR4. An isoleucine-to-proline
change (I559P) in the gp41 ectodomain has been used to stabilize soluble forms of
HIV-1 Env trimers for structural characterization and for use as immunogens. In
the native membrane-anchored HIV-1BG505 Env, the I559P change modestly decreased
proteolytic maturation, increased the non-covalent association of gp120 with the
Env trimer, and resulted in an Env conformation distinctly different from that of
the wild-type HIV-1BG505 Env. Compared with the wild-type Env, the I559P Env was
recognized inefficiently by polyclonal sera from HIV-1-infected individuals, by
several gp41-directed antibodies, by some antibodies against the CD4-binding site
of gp120, and by antibodies that preferentially recognize the CD4-bound Env. Some
of the gp120-associated antigenic differences between the wild-type HIV-1BG505
Env and the I559P mutant were compensated by the SOS disulfide bond between gp120
and gp41, which has been used to stabilize cleaved soluble Env trimers.
Nonetheless, regardless of the presence of the SOS changes, Envs with proline 559
were recognized less efficiently than Envs with isoleucine 559 by the VRC01
neutralizing antibody, which binds the CD4-binding site of gp120, and the PGT151
neutralizing antibody, which binds a hybrid gp120-gp41 epitope. The I559P change
completely eliminated the ability of the HIV-1BG505 Env to mediate cell-cell
fusion and virus entry, and abolished the capacity of the SOS Env to support
virus infection in the presence of a reducing agent. These results suggest that
differences exist between the quaternary structures of functional Env spikes and
I559P Envs.
PMID- 25849369
TI - Flexible n-type thermoelectric materials by organic intercalation of layered
transition metal dichalcogenide TiS2.
AB - Organic semiconductors are attracting increasing interest as flexible
thermoelectric materials owing to material abundance, easy processing and low
thermal conductivity. Although progress in p-type polymers and composites has
been reported, their n-type counterpart has fallen behind owing to difficulties
in n-type doping of organic semiconductors. Here, we present an approach to
synthesize n-type flexible thermoelectric materials through a facile
electrochemical intercalation method, fabricating a hybrid superlattice of
alternating inorganic TiS2 monolayers and organic cations. Electrons were
externally injected into the inorganic layers and then stabilized by organic
cations, providing n-type carriers for current and energy transport. An
electrical conductivity of 790 S cm(-1) and a power factor of 0.45 mW m(-1) K(-2)
were obtained for a hybrid superlattice of TiS2/[(hexylammonium)x(H2O)y(DMSO)z],
with an in-plane lattice thermal conductivity of 0.12 +/- 0.03 W m(-1) K(-1),
which is two orders of magnitude smaller than the thermal conductivities of the
single-layer and bulk TiS2. High power factor and low thermal conductivity
contributed to a thermoelectric figure of merit, ZT, of 0.28 at 373 K, which
might find application in wearable electronics.
PMID- 25849370
TI - Stabilizing triplet excited states for ultralong organic phosphorescence.
AB - The control of the emission properties of synthetic organic molecules through
molecular design has led to the development of high-performance optoelectronic
devices with tunable emission colours, high quantum efficiencies and efficient
energy/charge transfer processes. However, the task of generating excited states
with long lifetimes has been met with limited success, owing to the ultrafast
deactivation of the highly active excited states. Here, we present a design rule
that can be used to tune the emission lifetime of a wide range of luminescent
organic molecules, based on effective stabilization of triplet excited states
through strong coupling in H-aggregated molecules. Our experimental data revealed
that luminescence lifetimes up to 1.35 s, which are several orders of magnitude
longer than those of conventional organic fluorophores, can be realized under
ambient conditions. These results outline a fundamental principle to design
organic molecules with extended lifetimes of excited states, providing a major
step forward in expanding the scope of organic phosphorescence applications.
PMID- 25849371
TI - Gene expression profiles associated with pediatric relapsed AML.
AB - Development of relapse remains a problem for further improvements in the survival
of pediatric AML patients. While virtually all patients show a good response to
initial treatment, more patients respond poorly when treated at relapse. The
cellular characteristics of leukemic blast cells that allow survival of initial
treatment, relapse development and subsequent resistance to salvage treatment
remain largely elusive. Therefore, we studied if leukemic blasts at relapse
biologically resemble their initial diagnosis counterparts. We performed
microarray gene expression profiling on paired initial and relapse samples of 23
pediatric AML patients. In 11 out of 23 patients, gene expression profiles of
initial and corresponding relapse samples end up in different clusters in
unsupervised analysis, indicating altered gene expression profiles. In addition,
shifts in type I/II mutational status were found in 5 of these 11 patients, while
shifts were found in 3 of the remaining 12 patients. Although differentially
expressed genes varied between patients, they were commonly related to
hematopoietic differentiation, encompassed genes involved in chromatin remodeling
and showed associations with similar transcription factors. The top five were
CEBPA, GFI1, SATB1, KLF2 and TBP. In conclusion, the leukemic blasts at relapse
are biologically different from their diagnosis counterparts. These differences
may be exploited for further development of novel treatment strategies.
PMID- 25849372
TI - Apolipoprotein-A1 as a damage-associated molecular patterns protein in
osteoarthritis: ex vivo and in vitro pro-inflammatory properties.
AB - Osteoarthritis (OA) is associated with a local inflammatory process. Dyslipidemia
is known to be an underlying cause for the development of OA. Therefore, lipid
and inflammatory levels were quantified ex vivo in blood and synovial fluid of OA
patients (n=29) and compared to those of rheumatoid arthritis (RA) patients
(n=27) or healthy volunteers (HV) (n=35). The role of apolipoprotein A-I (ApoA1)
was investigated in vitro on inflammatory parameters using human joint cells
isolated from cartilage and synovial membrane obtained from OA patients after
joint replacement. Cells were stimulated with ApoA1 in the presence or not of
serum amyloid A (SAA) protein and/or lipoproteins (LDL and HDL) at physiological
concentration observed in OA synovial fluid. In our ex vivo study, ApoA1, LDL-C
and total cholesterol levels were strongly correlated to each other inside the OA
joint cavity whereas same levels were not or weakly correlated to their
corresponding serum levels. In OA synovial fluid, ApoA1 was not as strongly
correlated to HDL as observed in OA serum or in RA synovial fluid, suggesting a
dissociative level between ApoA1 and HDL in OA synovial fluid. In vitro, ApoA1
induced IL-6, MMP-1 and MMP-3 expression by primary chondrocytes and fibroblast
like synoviocytes through TLR4 receptor. HDL and LDL attenuated joint
inflammatory response induced by ApoA1 and SAA in a ratio dependent manner. In
conclusion, a dysregulated lipidic profile in the synovial fluid of OA patients
was observed and was correlated with inflammatory parameters in the OA joint
cavity. Pro-inflammatory properties of ApoA1 were confirmed in vitro.
PMID- 25849373
TI - Systematic functional profiling of transcription factor networks in Cryptococcus
neoformans.
AB - Cryptococcus neoformans causes life-threatening meningoencephalitis in humans,
but its overall biological and pathogenic regulatory circuits remain elusive,
particularly due to the presence of an evolutionarily divergent set of
transcription factors (TFs). Here, we report the construction of a high-quality
library of 322 signature-tagged gene-deletion strains for 155 putative TF genes
previously predicted using the DNA-binding domain TF database, and examine their
in vitro and in vivo phenotypic traits under 32 distinct growth conditions. At
least one phenotypic trait is exhibited by 145 out of 155 TF mutants (93%) and
~85% of them (132/155) are functionally characterized for the first time in this
study. The genotypic and phenotypic data for each TF are available in the C.
neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our
phenome-based functional analysis of the C. neoformans TF mutant library provides
key insights into transcriptional networks of basidiomycetous fungi and human
fungal pathogens.
PMID- 25849375
TI - Analysis of bias in measurements of potassium, sodium and hemoglobin by an
emergency department-based blood gas analyzer relative to hospital laboratory
autoanalyzer results.
AB - OBJECTIVE: The emergency departments (EDs) of Chinese hospitals are gradually
being equipped with blood gas machines. These machines, along with the
measurement of biochemical markers by the hospital laboratory, facilitate the
care of patients with severe conditions who present to the ED. However,
discrepancies have been noted between the Arterial Blood Gas (ABG) analyzers in
the ED and the hospital laboratory autoanalyzer in relation to electrolyte and
hemoglobin measurements. The present study was performed to determine whether the
ABG and laboratory measurements of potassium, sodium, and hemoglobin levels are
equivalent, and whether ABG analyzer results can be used to guide clinical care
before the laboratory results become available. MATERIALS AND METHODS: Study
power analyses revealed that 200 consecutive patients who presented to our ED
would allow this prospective single-center cohort study to detect significant
differences between ABG- and laboratory-measured potassium, sodium, and
hemoglobin levels. Paired arterial and venous blood samples were collected within
30 minutes. Arterial blood samples were measured in the ED by an ABL 90 FLEX
blood gas analyzer. The biochemistry and blood cell counts of the venous samples
were measured in the hospital laboratory. The potassium, sodium, and hemoglobin
concentrations obtained by both methods were compared by using paired Student's t
test, Spearman's correlation, Bland-Altman plots, and Deming regression. RESULTS:
The mean ABG and laboratory potassium values were 3.77+/-0.44 and 4.2+/-0.55,
respectively (P<0.0001). The mean ABG and laboratory sodium values were 137.89+/
5.44 and 140.93+/-5.50, respectively (P<0.0001). The mean ABG and laboratory
Hemoglobin values were 12.28+/-2.62 and 12.35+/-2.60, respectively (P = 0.24).
CONCLUSION: Although there are the statistical difference and acceptable biases
between ABG- and laboratory-measured potassium and sodium, the biases do not
exceed USCLIA-determined limits. In parallel, there are no statistical
differences and biases beyond USCLIA-determined limits between ABG- and
laboratory-measured hemoglobin. Therefore, all three variables measured by ABG
were reliable.
PMID- 25849374
TI - Transcriptional profiling of ectoderm specification to keratinocyte fate in human
embryonic stem cells.
AB - In recent years, several studies have shed light into the processes that regulate
epidermal specification and homeostasis. We previously showed that a broad
spectrum gamma-secretase inhibitor DAPT promoted early keratinocyte specification
in human embryonic stem cells triggered to undergo ectoderm specification. Here,
we show that DAPT accelerates human embryonic stem cell differentiation and
induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA
sequencing to identify several candidate regulators of ectoderm specification
including those involved in epithelial and epidermal development in human
embryonic stem cells. Genes associated with transcriptional regulation and growth
factor activity are significantly enriched upon DAPT treatment during
specification of human embryonic stem cells to the ectoderm lineage. The human
ectoderm cell signature identified in this study contains several genes expressed
in ectodermal and epithelial tissues. Importantly, these genes are also
associated with skin disorders and ectodermal defects, providing a platform for
understanding the biology of human epidermal keratinocyte development under
diseased and homeostatic conditions.
PMID- 25849376
TI - Proteomic analysis of mice fed methionine and choline deficient diet reveals
marker proteins associated with steatohepatitis.
AB - The mechanisms underlying the progression of simple steatosis to steatohepatitis
are yet to be elucidated. To identify the proteins involved in the development of
liver tissue inflammation, we performed comparative proteomic analysis of non
alcoholic steatohepatitis (NASH). Mice fed a methionine and choline deficient
diet (MCD) developed hepatic steatosis characterized by increased free fatty acid
(FFA) and triglyceride levels as well as alpha-SMA. Two-dimensional proteomic
analysis revealed that the change from the normal diet to the MCD diet affected
the expressions of 50 proteins. The most-pronounced changes were observed in the
expression of proteins involved in Met metabolism and oxidative stress, most of
which were significantly downregulated in NASH model animals. Peroxiredoxin (Prx)
is the most interesting among the modulated proteins identified in this study. In
particular, cross-regulated Prx1 and Prx6 are likely to participate in cellular
defense against the development of hepatitis. Thus, these Prx isoforms may be a
useful new marker for early stage steatohepatitis. Moreover, curcumin treatment
results in alleviation of the severity of hepatic inflammation in
steatohepatitis. Notably, curcumin administration in MCD-fed mice dramatically
reduced CYP2E1 as well as Prx1 expression, while upregulating Prx6 expression.
These findings suggest that curcumin may have a protective role against MCD fed
induced oxidative stress.
PMID- 25849377
TI - Suppressor of cytokine signaling (SOCS) genes are silenced by DNA
hypermethylation and histone deacetylation and regulate response to radiotherapy
in cervical cancer cells.
AB - Suppressor of cytokine signaling (SOCS) family is an important negative regulator
of cytokine signaling and deregulation of SOCS has been involved in many types of
cancer. All cervical cancer cell lines tested showed lower expression of SOCS1,
SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry
result for SOCS proteins in human cervical tissue also confirmed that normal
tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to
the regulation of SOCS in other types of cancer, DNA methylation contributed to
SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of
SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone
deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3
expression, however, SOCS5 expression was neither affected by DNA methylation nor
histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred
radioresistance to HeLa cells, which implied SOCS signaling regulates the
response to radiation in cervical cancer. In this study, we have shown that SOCS
expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3
expression could contribute to the radiosensitive phenotype in cervical cancer.
PMID- 25849378
TI - Haberlea rhodopensis: pharmaceutical and medical potential as a food additive.
AB - This review discusses the potential of Haberlea rhodopensis as a food additive.
The following are described: plant distribution, reproduction, cultivation,
propagation and resurrection properties; extraction, isolation and screening of
biologically active compounds; metabolite changes during dehydration;
phytotherapy-related properties such as antioxidant potential and free radical
scavenging activities, antioxidant skin effect, antibacterial activity, cytotoxic
activity and cancer-modulating effect, radioprotective effect, chemoprotective
effect, immunologic effect; present use in homoeopathy and cosmetics,
pharmacological and economical importance; perspectives based on the
ethnobotanical data for medicinal, cosmetic or ritual attributes. H. rhodopensis
showed unique medical and pharmaceutical potential, related to antioxidant,
antimicrobial, antimutagenic, anticancer, radioprotective, chemoprotective and
immunological properties. H. rhodopensis extracts lack any cytotoxic activity and
could be used in phytotherapy. The metabolic profiling of H. rhodopensis extracts
revealed the presence of biologically active compounds, possessing antiradical
and other physiological activities, useful for design of in vitro synthesised
analogues and drugs.
PMID- 25849379
TI - Lgr5+ cells regenerate hair cells via proliferation and direct
transdifferentiation in damaged neonatal mouse utricle.
AB - Recruitment of endogenous progenitors is critical during tissue repair. The inner
ear utricle requires mechanosensory hair cells (HCs) to detect linear
acceleration. After damage, non-mammalian utricles regenerate HCs via both
proliferation and direct transdifferentiation. In adult mammals, limited
transdifferentiation from unidentified progenitors occurs to regenerate
extrastriolar Type II HCs. Here we show that HC damage in neonatal mouse utricle
activates the Wnt target gene Lgr5 in striolar supporting cells. Lineage tracing
and time-lapse microscopy reveal that Lgr5+ cells transdifferentiate into HC-like
cells in vitro. In contrast to adults, HC ablation in neonatal utricles in vivo
recruits Lgr5+ cells to regenerate striolar HCs through mitotic and
transdifferentiation pathways. Both Type I and II HCs are regenerated, and
regenerated HCs display stereocilia and synapses. Lastly, stabilized beta-catenin
in Lgr5+ cells enhances mitotic activity and HC regeneration. Thus Lgr5 marks Wnt
regulated, damage-activated HC progenitors and may help uncover factors driving
mammalian HC regeneration.
PMID- 25849381
TI - Comparison of astigmatic correction after femtosecond lenticule extraction and
small-incision lenticule extraction for myopic astigmatism.
AB - PURPOSE: To compare postoperative astigmatic correction between femtosecond
lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE) in
eyes with myopic astigmatism. METHODS: We examined 26 eyes of 26 patients
undergoing FLEx and 26 eyes of 26 patients undergoing SMILE to correct myopic
astigmatism (manifest astigmatism of 1 diopter (D) or more). Visual acuity,
cylindrical refraction, the predictability of the astigmatic correction, and the
astigmatic vector components using Alpin's method, were compared between the two
groups 3 months postoperatively. RESULTS: We found no statistically significant
difference in manifest cylindrical refraction (p=0.74) or in the percentage of
eyes within +/- 0.50 D of their refraction (p=0.47) after the two surgical
procedures. Moreover, no statistically significant difference was detected
between the groups in astigmatic vector components, namely, surgically induced
astigmatism (0.80), target induced astigmatism (p=0.87), astigmatic correction
index (p=0.77), angle of error (p=0.24), difference vector (p=0.76), index of
success (p=0.91), flattening effect (p=0.79), and flattening index (p=0.84).
CONCLUSIONS: Both FLEx and SMILE procedures are essentially equivalent in
correcting myopic astigmatism using vector analysis, suggesting that the lifting
or non-lifting of the flap does not significantly affect astigmatic outcomes
after these surgical procedures.
PMID- 25849380
TI - Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling
through connexin43-mediated Ca2+ influx.
AB - BACKGROUND: The prevalence of obesity has dramatically increased worldwide and
has attracted rising attention, but the mechanism is still unclear. Previous
studies revealed that transient receptor potential vanilloid 1 (TRPV1) channels
take part in weight loss by enhancing intracellular Ca2+ levels. However, the
potential mechanism of the effect of dietary capsaicin on obesity is not
completely understood. Ca2+ transfer induced by connexin43 (Cx43) molecules
between coupled cells takes part in adipocyte differentiation. Whether TRPV1
evoked alterations in Cx43-mediated adipocyte-to-adipocyte communication play a
role in obesity is unknown. MATERIALS AND METHODS: We investigated whether Cx43
participated in TRPV1-mediated adipocyte lipolysis in cultured 3T3-L1
preadipocytes and visceral adipose tissues from humans and wild-type (WT) and
TRPV1-deficient (TRPV1-/-) mice. RESULTS: TRPV1 and Cx43 co-expressed in
mesenteric adipose tissue. TRPV1 activation by capsaicin increased the influx of
Ca2+ in 3T3-L1 preadipocytes and promoted cell lipolysis, as shown by Oil-red O
staining. These effects were deficient when capsazepine, a TRPV1 antagonist, and
18 alpha-glycyrrhetinic acid (18alpha-GA), a gap-junction inhibitor, were
administered. Long-term chronic dietary capsaicin reduced the weights of
perirenal, mesenteric and testicular adipose tissues in WT mice fed a high-fat
diet. Capsaicin increased the expression levels of p-CaM, Cx43, CaMKII, PPARdelta
and HSL in mesenteric adipose tissues from WT mice fed a high-fat diet, db/db
mice, as well as obese humans, but these effects of capsaicin were absent in
TRPV1-/- mice. Long-term chronic dietary capsaicin decreased the body weights and
serum lipids of WT mice, but not TRPV1-/- mice, fed a high-fat diet. CONCLUSION:
This study demonstrated that capsaicin activation of TRPV1-evoked increased Ca2+
influx in Cx43-mediated adipocyte-to-adipocyte communication promotes lipolysis
in both vitro and vivo. TRPV1 activation by dietary capsaicin improves visceral
fat remodeling through the up-regulation of Cx43.
PMID- 25849382
TI - The nematicidal effect of camellia seed cake on root-knot nematode Meloidogyne
javanica of banana.
AB - Suppression of root-knot nematodes is crucially important for maintaining the
worldwide development of the banana industry. Growing concerns about human and
environmental safety have led to the withdrawal of commonly used nematicides and
soil fumigants, thus motivating the development of alternative nematode
management strategies. In this study, Meloidogyne javanica was isolated, and the
nematicidal effect of Camellia seed cake on this pest was investigated. The
results showed that in dish experiments, Camellia seed cake extracts under low
concentration (2 g/L) showed a strong nematicidal effect. After treatment for 72
h, the eggs of M. javanica were gradually dissolved, and the intestine of the
juveniles gradually became indistinct. Nematicidal compounds, including saponins
identified by HPLC-ESI-MS and 8 types of volatile compounds identified by GC-MS,
exhibited effective nematicidal activities, especially 4-methylphenol. The pot
experiments demonstrated that the application of Camellia seed cake suppressed M.
javanica, and promoted the banana plant growth. This study explored an effective
nematicidal agent for application in soil and revealed its potential mechanism of
nematode suppression.
PMID- 25849384
TI - Enhanced Photoreduction CO2 Activity over Direct Z-Scheme alpha-Fe2O3/Cu2O
Heterostructures under Visible Light Irradiation.
AB - Hematite-cuprous oxide (alpha-Fe2O3/Cu2O) nanocomposites are synthesized based on
the design of Z-scheme photocatalyst for CO2 reduction. The band structure for
the typical Fe2O3/Cu2O (with 1:1 mole ratio) is characterized by UV-vis
reflectance spectroscopy and X-ray/ultraviolet photoelectron spectroscopy, and
its heterojunction is determined to be Type II band alignment. The photoreduction
CO2 activities of the heterostructures are investigated in the presence of water
vapor. The CO yields are changed with Fe/Cu mole ratio, and the maximal CO yield
attains 5.0 MUmol.g cat(-1) after 3 h of visible-light irradiation. Besides the
effect of light wavelength, H2O/CO2 molar ratio and temperature on the products
is studied. The selectivity of the prepared catalysts is tunable by modulating
the light wavelength. The reaction mechanism is proposed and further confirmed
experimentally. The results gained herein may provide some insights into the
design of Z-scheme photocatalysts for CO2 reduction.
PMID- 25849383
TI - Is a cancer diagnosis associated with subsequent risk of transient global
amnesia?
AB - BACKGROUND: Psychological stress has been associated with transient global
amnesia (TGA). Whether a cancer diagnosis, a severely stressful life event, is
associated with subsequent risk of TGA has not been studied. METHODS: Based on
the Swedish Cancer Register and Patient Register, we conducted a prospective
cohort study including 5,365,608 Swedes at age 30 and above during 2001-2009 to
examine the relative risk of TGA among cancer patients, as compared to cancer
free individuals. Incidence rate ratios (IRRs) and their 95% confidence intervals
(CIs) derived from Poisson regression were used as estimates of the association
between cancer diagnosis and the risk of TGA. RESULTS: During the study 322,558
individuals (6.01%) received a first diagnosis of cancer. We identified 210 cases
of TGA among the cancer patients (incidence rate, 0.22 per 1000 person-years) and
4,887 TGA cases among the cancer-free individuals (incidence rate, 0.12 per 1000
person-years). Overall, after adjustment for age, sex, calendar year,
socioeconomic status, education and civil status, cancer patients had no
increased risk of TGA than the cancer-free individuals (IRR, 0.99; 95% CI, 0.86
1.13). The IRRs did not differ over time since cancer diagnosis or across
individual cancer types. The null association was neither modified by sex,
calendar period or age. CONCLUSION: Our study did not provide support for the
hypothesis that patients with a new diagnosis of cancer display a higher risk of
TGA than cancer-free individuals.
PMID- 25849386
TI - Structure of N-myristoyltransferase from Aspergillus fumigatus.
AB - N-Myristoyltransferase (NMT) is an enzyme which translocates the 14-carbon
saturated fatty acid myristate from myristoyl-CoA to the N-terminal glycine of
substrate peptides. This myristoylation process is involved in protein
modification in various eukaryotes, including animals and fungi. Furthermore,
this enzyme has been shown to be essential to the growth of various species, such
as Saccharomyces cerevisiae, which indicates that NMT is an attractive target for
the development of a novel antifungal drug. In this study, the crystal structure
of a ternary complex of NMT from Aspergillus fumigatus with S-(2-oxo)pentadecyl
CoA, a myristoyl-CoA analogue cofactor, and a synthetic inhibitor is reported at
a resolution of 2.1 A. The results advance the understanding of the specificity
of NMT inhibitors and provide valuable information for structure-based drug
design.
PMID- 25849385
TI - High-pressure protein crystallography of hen egg-white lysozyme.
AB - Crystal structures of hen egg-white lysozyme (HEWL) determined under pressures
ranging from ambient pressure to 950 MPa are presented. From 0.1 to 710 MPa, the
molecular and internal cavity volumes are monotonically compressed. However, from
710 to 890 MPa the internal cavity volume remains almost constant. Moreover, as
the pressure increases to 950 MPa, the tetragonal crystal of HEWL undergoes a
phase transition from P43212 to P43. Under high pressure, the crystal structure
of the enzyme undergoes several local and global changes accompanied by changes
in hydration structure. For example, water molecules penetrate into an internal
cavity neighbouring the active site and induce an alternate conformation of one
of the catalytic residues, Glu35. These phenomena have not been detected by
conventional X-ray crystal structure analysis and might play an important role in
the catalytic activity of HEWL.
PMID- 25849388
TI - Radiation decay of thaumatin crystals at three X-ray energies.
AB - Radiation damage is an unavoidable obstacle in X-ray crystallographic data
collection for macromolecular structure determination, so it is important to know
how much radiation a sample can endure before being degraded beyond an acceptable
limit. In the literature, the threshold at which the average intensity of all
recorded reflections decreases to a certain fraction of the initial value is
called the 'dose limit'. The first estimated D50 dose-limit value, at which the
average diffracted intensity was reduced to 50%, was 20 MGy and was derived from
observing sample decay in electron-diffraction experiments. A later X-ray study
carried out at 100 K on ferritin protein crystals arrived at a D50 of 43 MGy, and
recommended an intensity reduction of protein reflections to 70%, D70,
corresponding to an absorbed dose of 30 MGy, as a more appropriate limit for
macromolecular crystallography. In the macromolecular crystallography community,
the rate of intensity decay with dose was then assumed to be similar for all
protein crystals. A series of diffraction images of cryocooled (100 K) thaumatin
crystals at identical small, 2 degrees rotation intervals were recorded at X-ray
energies of 6.33 , 12.66 and 19.00 keV. Five crystals were used for each
wavelength. The decay in the average diffraction intensity to 70% of the initial
value, for data extending to 2.45 A resolution, was determined to be about 7.5
MGy at 6.33 keV and about 11 MGy at the two higher energies.
PMID- 25849387
TI - A noncanonical PWI domain in the N-terminal helicase-associated region of the
spliceosomal Brr2 protein.
AB - The spliceosomal RNA helicase Brr2 is required for the assembly of a
catalytically active spliceosome on a messenger RNA precursor. Brr2 exhibits an
unusual organization with tandem helicase units, each comprising dual RecA-like
domains and a Sec63 homology unit, preceded by a more than 400-residue N-terminal
helicase-associated region. Whereas recent crystal structures have provided
insights into the molecular architecture and regulation of the Brr2 helicase
region, little is known about the structural organization and function of its N
terminal part. Here, a near-atomic resolution crystal structure of a PWI-like
domain that resides in the N-terminal region of Chaetomium thermophilum Brr2 is
presented. CD spectroscopic studies suggested that this domain is conserved in
the yeast and human Brr2 orthologues. Although canonical PWI domains act as low
specificity nucleic acid-binding domains, no significant affinity of the unusual
PWI domain of Brr2 for a broad spectrum of DNAs and RNAs was detected in band
shift assays. Consistently, the C. thermophilum Brr2 PWI-like domain, in the
conformation seen in the present crystal structure, lacks an expanded positively
charged surface patch as observed in at least one canonical, nucleic acid-binding
PWI domain. Instead, in a comprehensive yeast two-hybrid screen against human
spliceosomal proteins, fragments of the N-terminal region of human Brr2 were
found to interact with several other spliceosomal proteins. At least one of these
interactions, with the Prp19 complex protein SPF27, depended on the presence of
the PWI-like domain. The results suggest that the N-terminal region of Brr2
serves as a versatile protein-protein interaction platform in the spliceosome and
that some interactions require or are reinforced by the PWI-like domain.
PMID- 25849389
TI - Structure of a double-domain phosphagen kinase reveals an asymmetric arrangement
of the tandem domains.
AB - Tandem duplications and fusions of single genes have led to magnificent
expansions in the divergence of protein structures and functions over
evolutionary timescales. One of the possible results is polydomain enzymes with
interdomain cooperativities, few examples of which have been structurally
characterized at the full-length level to explore their innate synergistic
mechanisms. This work reports the crystal structures of a double-domain
phosphagen kinase in both apo and ligand-bound states, revealing a novel
asymmetric L-shaped arrangement of the two domains. Unexpectedly, the interdomain
connections are not based on a flexible hinge linker but on a rigid secondary
structure element: a long alpha-helix that tethers the tandem domains in
relatively fixed positions. Besides the connective helix, the two domains also
contact each other directly and form an interdomain interface in which hydrogen
bonds and hydrophobic interactions further stabilize the L-shaped domain
arrangement. Molecular-dynamics simulations show that the interface is generally
stable, suggesting that the asymmetric domain arrangement crystallographically
observed in the present study is not a conformational state simply restrained by
crystal-packing forces. It is possible that the asymmetrically arranged tandem
domains could provide a structural basis for further studies of the interdomain
synergy.
PMID- 25849390
TI - The crystal structure of phosphorylated MAPK13 reveals common structural features
and differences in p38 MAPK family activation.
AB - The p38 MAP kinases (p38 MAPKs) represent an important family centrally involved
in mediating extracellular signaling. Recent studies indicate that family members
such as MAPK13 (p38delta) display a selective cellular and tissue expression and
are therefore involved in specific diseases. Detailed structural studies of all
p38 MAPK family members are crucial for the design of specific inhibitors. In
order to facilitate such ventures, the structure of MAPK13 was determined in both
the inactive (unphosphorylated; MAPK13) and active (dual phosphorylated;
MAPK13/pTpY) forms. Here, the first preparation, crystallization and structure
determination of MAPK13/pTpY are presented and the structure is compared with the
previously reported structure of MAPK13 in order to facilitate studies for
structure-based drug design. A comprehensive analysis of inactive versus active
structures for the p38 MAPK family is also presented. It is found that MAPK13
undergoes a larger interlobe configurational rearrangement upon activation
compared with MAPK14. Surprisingly, the analysis of activated p38 MAPK structures
(MAP12/pTpY, MAPK13/pTpY and MAPK14/pTpY) reveals that, despite a high degree of
sequence similarity, different side chains are used to coordinate the
phosphorylated residues. There are also differences in the rearrangement of the
hinge region that occur in MAPK14 compared with MAPK13 which would affect
inhibitor binding. A thorough examination of all of the active (phosphorylated)
and inactive (unphosphorylated) p38 MAPK family member structures was performed
to reveal a common structural basis of activation for the p38 MAP kinase family
and to identify structural differences that may be exploited for developing
family member-specific inhibitors.
PMID- 25849391
TI - Structure of Arabidopsis thaliana Rubisco activase.
AB - The CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco)
is inactivated by the formation of dead-end complexes with inhibitory sugar
phosphates. In plants and green algae, the ATP-dependent motor protein Rubisco
activase restores catalytic competence by facilitating conformational changes in
Rubisco that promote the release of the inhibitory compounds from the active
site. Here, the crystal structure of Rubisco activase from Arabidopsis thaliana
is presented at 2.9 A resolution. The structure reveals an AAA+ two-domain
structure. More than 100 residues in the protein were not visible in the electron
density map owing to conformational disorder, but were verified to be present in
the crystal by mass spectrometry. Two sulfate ions were found in the structure.
One was bound in the loop formed by the Walker A motif at the interface of the
domains. A second sulfate ion was bound at the N-terminal end of the first helix
of the C-terminal domain. The protein packs in a helical fashion in the crystal,
as observed previously for Rubisco activase, but differences in the helical pitch
indicate flexibility in the packing of the protein.
PMID- 25849392
TI - Structure of struthiocalcin-1, an intramineral protein from Struthio camelus
eggshell, in two crystal forms.
AB - Biomineralization is the process by which living organisms produce minerals. One
remarkable example is the formation of eggshells in birds. Struthiocalcins
present in the ostrich (Struthio camellus) eggshell matrix act as biosensors of
calcite growth during eggshell formation. Here, the crystal structure of
struthiocalcin-1 (SCA-1) is reported in two different crystal forms. The
structure is a compact single domain with an alpha/beta fold characteristic of
the C-type lectin family. In contrast to the related avian ovocleidin OC17, the
electrostatic potential on the molecular surface is dominated by an acidic patch.
Scanning electron microscopy combined with Raman spectroscopy indicates that
these intramineral proteins (SCA-1 and SCA-2) induce calcium carbonate
precipitation, leading to the formation of a stable form of calcite in the mature
eggshell. Finally, the implications of these two intramineral proteins SCA-1 and
SCA-2 in the nucleation of calcite during the formation of eggshells in ratite
birds are discussed.
PMID- 25849393
TI - Novel crystalline phase and first-order phase transitions of human insulin
complexed with two distinct phenol derivatives.
AB - The primary focus of the present work is the study of the effects that two
ligands and the crystallization pH have on the crystalline forms of human
insulin. For this purpose, human insulin (HI) was co-crystallized with two
distinct phenolic derivatives: the organic ligands meta-cresol (m-cresol) and 4
nitrophenol. The formation of polycrystalline precipitates was then followed by
means of structural characterization of the individual specimens in terms of unit
cell symmetry and parameters. In both cases, two different polymorphs were
identified via X-ray powder diffraction measurements, the first of hexagonal
symmetry (R3 space group) at higher pH values and the second of monoclinic
symmetry (space group P21) with unit-cell parameters a = 87.4282 (5), b = 70.5020
(3), c = 48.3180 (4) A, beta = 106.8958 (4) degrees , the latter of which to our
knowledge has never been observed before.
PMID- 25849394
TI - ANS complex of St John's wort PR-10 protein with 28 copies in the asymmetric
unit: a fiendish combination of pseudosymmetry with tetartohedral twinning.
AB - Hyp-1, a pathogenesis-related class 10 (PR-10) protein from St John's wort
(Hypericum perforatum), was crystallized in complex with the fluorescent probe 8
anilino-1-naphthalene sulfonate (ANS). The highly pseudosymmetric crystal has 28
unique protein molecules arranged in columns with sevenfold translational
noncrystallographic symmetry (tNCS) along c and modulated X-ray diffraction with
intensity crests at l = 7n and l = 7n +/- 3. The translational NCS is combined
with pseudotetragonal rotational NCS. The crystal was a perfect tetartohedral
twin, although detection of twinning was severely hindered by the pseudosymmetry.
The structure determined at 2.4 A resolution reveals that the Hyp-1 molecules
(packed as beta-sheet dimers) have three novel ligand-binding sites (two internal
and one in a surface pocket), which was confirmed by solution studies. In
addition to 60 Hyp-1-docked ligands, there are 29 interstitial ANS molecules
distributed in a pattern that violates the arrangement of the protein molecules
and is likely to be the generator of the structural modulation. In particular,
whenever the stacked Hyp-1 molecules are found closer together there is an ANS
molecule bridging them.
PMID- 25849396
TI - Elucidation of the crystal structure of Coriolopsis caperata laccase: restoration
of the structure and activity of the native enzyme from the T2-depleted form by
copper ions.
AB - Laccases are members of a large family of multicopper oxidases that catalyze the
oxidation of a wide range of organic and inorganic substrates accompanied by the
reduction of dioxygen to water. A new laccase was isolated from the basidiomycete
Coriolopsis caperata strain 0677 and its amino-acid sequence was determined.
According to its physicochemical properties and spectroscopic features, the
laccase from C. caperata is a high redox-potential blue laccase. Attempts to
crystallize the native enzyme were unsuccessful. The copper type 2-depleted (T2D)
laccase was prepared and crystallized. The structure of T2D laccase from C.
caperata was solved at 1.6 A resolution, and attempts to reconstruct the T2
copper centre were performed using Cu(+) and Cu(2+) ions. The structure of
T2D+Cu(+) laccase was solved at 1.89 A resolution. It was shown that the
T2D+Cu(+) laccase structure contained four copper ions in the active site.
Reconstruction could not be achieved when the T2D laccase crystals were treated
with CuSO4.
PMID- 25849395
TI - Structure of the N-terminal domain of the protein Expansion: an 'Expansion' to
the Smad MH2 fold.
AB - Gene-expression changes observed in Drosophila embryos after inducing the
transcription factor Tramtrack led to the identification of the protein
Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2
domain characteristic of Smad proteins, which are the central mediators of the
effects of the TGF-beta signalling pathway. Apart from Smads and Expansion, no
other type of protein belonging to the known kingdoms of life contains MH2
domains. To compare the Expansion and Smad MH2 domains, the crystal structure of
the Expansion domain was determined at 1.6 A resolution, the first structure of a
non-Smad MH2 domain to be characterized to date. The structure displays the main
features of the canonical MH2 fold with two main differences: the addition of an
alpha-helical region and the remodelling of a protein-interaction site that is
conserved in the MH2 domain of Smads. Owing to these differences, to the new
domain was referred to as Nalpha-MH2. Despite the presence of the Nalpha-MH2
domain, Expansion does not participate in TGF-beta signalling; instead, it is
required for other activities specific to the protostome phyla. Based on the
structural similarities to the MH2 fold, it is proposed that the Nalpha-MH2
domain should be classified as a new member of the Smad/FHA superfamily.
PMID- 25849397
TI - A covalent adduct of MbtN, an acyl-ACP dehydrogenase from Mycobacterium
tuberculosis, reveals an unusual acyl-binding pocket.
AB - Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis. Access
to iron in host macrophages depends on iron-chelating siderophores called
mycobactins and is strongly correlated with Mtb virulence. Here, the crystal
structure of an Mtb enzyme involved in mycobactin biosynthesis, MbtN, in complex
with its FAD cofactor is presented at 2.30 A resolution. The polypeptide fold of
MbtN conforms to that of the acyl-CoA dehydrogenase (ACAD) family, consistent
with its predicted role of introducing a double bond into the acyl chain of
mycobactin. Structural comparisons and the presence of an acyl carrier protein,
MbtL, in the same gene locus suggest that MbtN acts on an acyl-(acyl carrier
protein) rather than an acyl-CoA. A notable feature of the crystal structure is
the tubular density projecting from N(5) of FAD. This was interpreted as a
covalently bound polyethylene glycol (PEG) fragment and resides in a hydrophobic
pocket where the substrate acyl group is likely to bind. The pocket could
accommodate an acyl chain of 14-21 C atoms, consistent with the expected length
of the mycobactin acyl chain. Supporting this, steady-state kinetics show that
MbtN has ACAD activity, preferring acyl chains of at least 16 C atoms. The acyl
binding pocket adopts a different orientation (relative to the FAD) to other
structurally characterized ACADs. This difference may be correlated with the
apparent ability of MbtN to catalyse the formation of an unusual cis double bond
in the mycobactin acyl chain.
PMID- 25849398
TI - Structure of the adenylation-peptidyl carrier protein didomain of the Microcystis
aeruginosa microcystin synthetase McyG.
AB - Microcystins, which are the most common cause of hepatotoxicity associated with
cyanobacterial water blooms, are assembled in vivo on a large multienzyme complex
via a mixed nonribosomal peptide synthetase/polyketide synthetase (NRPS/PKS). The
biosynthesis of microcystin in Microcystis aeruginosa PCC 7806 starts with the
enzyme McyG, which contains an adenylation-peptidyl carrier protein (A-PCP)
didomain for loading the starter unit to assemble the side chain of an Adda
residue. However, the catalytic mechanism remains unclear. Here, the 2.45 A
resolution crystal structure of the McyG A-PCP didomain complexed with the
catalytic intermediate L-phenylalanyl-adenylate (L-Phe-AMP) is reported. Each
asymmetric unit contains two protein molecules, one of which consists of the A
PCP didomain and the other of which comprises only the A domain. Structural
analyses suggest that Val227 is likely to be critical for the selection of
hydrophobic substrates. Moreover, two distinct interfaces demonstrating variable
crosstalk between the PCP domain and the A domain were observed. A catalytic
cycle for the adenylation and peptide transfer of the A-PCP didomain is proposed.
PMID- 25849399
TI - The architecture of amyloid-like peptide fibrils revealed by X-ray scattering,
diffraction and electron microscopy.
AB - Structural analysis of protein fibrillation is inherently challenging. Given the
crucial role of fibrils in amyloid diseases, method advancement is urgently
needed. A hybrid modelling approach is presented enabling detailed analysis of a
highly ordered and hierarchically organized fibril of the GNNQQNY peptide
fragment of a yeast prion protein. Data from small-angle X-ray solution
scattering, fibre diffraction and electron microscopy are combined with existing
high-resolution X-ray crystallographic structures to investigate the fibrillation
process and the hierarchical fibril structure of the peptide fragment. The
elongation of these fibrils proceeds without the accumulation of any detectable
amount of intermediate oligomeric species, as is otherwise reported for, for
example, glucagon, insulin and alpha-synuclein. Ribbons constituted of linearly
arranged protofilaments are formed. An additional hierarchical layer is generated
via the pairing of ribbons during fibril maturation. Based on the complementary
data, a quasi-atomic resolution model of the protofilament peptide arrangement is
suggested. The peptide structure appears in a beta-sheet arrangement reminiscent
of the beta-zipper structures evident from high-resolution crystal structures,
with specific differences in the relative peptide orientation. The complexity of
protein fibrillation and structure emphasizes the need to use multiple
complementary methods.
PMID- 25849401
TI - Structure and catalytic mechanism of the evolutionarily unique bacterial chalcone
isomerase.
AB - Flavonoids represent a large class of secondary metabolites produced by plants.
These polyphenolic compounds are well known for their antioxidative abilities,
are antimicrobial phytoalexins responsible for flower pigmentation to attract
pollinators and, in addition to other properties, are also specific bacterial
regulators governing the expression of Rhizobium genes involved in root
nodulation (Firmin et al., 1986). The bacterial chalcone isomerase (CHI) from
Eubacterium ramulus catalyses the first step in a flavanone-degradation pathway
by ring opening of (2S)-naringenin to form naringenin chalcone. The structural
biology and enzymology of plant CHIs have been well documented, whereas the
existence of bacterial CHIs has only recently been elucidated. This first
determination of the structure of a bacterial CHI provides detailed structural
insights into the key step of the flavonoid-degradation pathway. The active site
could be confirmed by co-crystallization with the substrate (2S)-naringenin. The
stereochemistry of the proposed mechanism of the isomerase reaction was verified
by specific (1)H/(2)H isotope exchange observed by (1)H NMR experiments and was
further supported by mutagenesis studies. The active site is shielded by a
flexible lid, the varying structure of which could be modelled in different
states of the catalytic cycle using small-angle X-ray scattering data together
with the crystallographic structures. Comparison of bacterial CHI with the plant
enzyme from Medicago sativa reveals that they have unrelated folds, suggesting
that the enzyme activity evolved convergently from different ancestor proteins.
Despite the lack of any functional relationship, the tertiary structure of the
bacterial CHI shows similarities to the ferredoxin-like fold of a chlorite
dismutase and the stress-related protein SP1.
PMID- 25849400
TI - Structural and biophysical characterization of an epitope-specific engineered Fab
fragment and complexation with membrane proteins: implications for co
crystallization.
AB - Crystallization chaperones are attracting increasing interest as a route to
crystal growth and structure elucidation of difficult targets such as membrane
proteins. While strategies to date have typically employed protein-specific
chaperones, a peptide-specific chaperone to crystallize multiple cognate peptide
epitope-containing client proteins is envisioned. This would eliminate the target
specific chaperone-production step and streamline the co-crystallization process.
Previously, protein engineering and directed evolution were used to generate a
single-chain variable (scFv) antibody fragment with affinity for the peptide
sequence EYMPME (scFv/EE). This report details the conversion of scFv/EE to an
anti-EE Fab format (Fab/EE) followed by its biophysical characterization. The
addition of constant chains increased the overall stability and had a negligible
impact on the antigen affinity. The 2.0 A resolution crystal structure of Fab/EE
reveals contacts with larger surface areas than those of scFv/EE. Surface plasmon
resonance, an enzyme-linked immunosorbent assay, and size-exclusion
chromatography were used to assess Fab/EE binding to EE-tagged soluble and
membrane test proteins: namely, the beta-barrel outer membrane protein intimin
and alpha-helical A2a G protein-coupled receptor (A2aR). Molecular-dynamics
simulation of the intimin constructs with and without Fab/EE provides insight
into the energetic complexities of the co-crystallization approach.
PMID- 25849402
TI - Structures of complexes of type 5 17beta-hydroxysteroid dehydrogenase with
structurally diverse inhibitors: insights into the conformational changes upon
inhibitor binding.
AB - Type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD5) is an aldo-keto
reductase expressed in the human prostate which catalyzes the conversion of
androstenedione to testosterone. Testosterone is converted to 5alpha
dihydrotestosterone, which is present at high concentrations in patients with
castration-resistant prostate cancer (CRPC). Inhibition of 17beta-HSD5 is
therefore considered to be a promising therapy for treating CRPC. In the present
study, crystal structures of complexes of 17beta-HSD5 with structurally diverse
inhibitors derived from high-throughput screening were determined. In the
structures of the complexes, various functional groups, including amide, nitro,
pyrazole and hydroxyl groups, form hydrogen bonds to the catalytic residues
His117 and Tyr55. In addition, major conformational changes of 17beta-HSD5 were
observed following the binding of the structurally diverse inhibitors. These
results demonstrate interactions between 17beta-HSD5 and inhibitors at the atomic
level and enable structure-based drug design for anti-CRPC therapy.
PMID- 25849403
TI - Capture and X-ray diffraction studies of protein microcrystals in a microfluidic
trap array.
AB - X-ray free-electron lasers (XFELs) promise to enable the collection of
interpretable diffraction data from samples that are refractory to data
collection at synchrotron sources. At present, however, more efficient sample
delivery methods that minimize the consumption of microcrystalline material are
needed to allow the application of XFEL sources to a wide range of challenging
structural targets of biological importance. Here, a microfluidic chip is
presented in which microcrystals can be captured at fixed, addressable points in
a trap array from a small volume (<10 ul) of a pre-existing slurry grown off
chip. The device can be mounted on a standard goniostat for conducting
diffraction experiments at room temperature without the need for flash-cooling.
Proof-of-principle tests with a model system (hen egg-white lysozyme)
demonstrated the high efficiency of the microfluidic approach for crystal
harvesting, permitting the collection of sufficient data from only 265 single
crystal still images to permit determination and refinement of the structure of
the protein. This work shows that microfluidic capture devices can be readily
used to facilitate data collection from protein microcrystals grown in
traditional laboratory formats, enabling analysis when cryopreservation is
problematic or when only small numbers of crystals are available. Such
microfluidic capture devices may also be useful for data collection at
synchrotron sources.
PMID- 25849405
TI - Cholesterol oxidase: ultrahigh-resolution crystal structure and multipolar atom
model-based analysis.
AB - Examination of protein structure at the subatomic level is required to improve
the understanding of enzymatic function. For this purpose, X-ray diffraction data
have been collected at 100 K from cholesterol oxidase crystals using synchrotron
radiation to an optical resolution of 0.94 A. After refinement using the
spherical atom model, nonmodelled bonding peaks were detected in the Fourier
residual electron density on some of the individual bonds. Well defined bond
density was observed in the peptide plane after averaging maps on the residues
with the lowest thermal motion. The multipolar electron density of the protein
cofactor complex was modelled by transfer of the ELMAM2 charge-density database,
and the topology of the intermolecular interactions between the protein and the
flavin adenine dinucleotide (FAD) cofactor was subsequently investigated. Taking
advantage of the high resolution of the structure, the stereochemistry of main
chain bond lengths and of C=O...H-N hydrogen bonds was analyzed with respect to
the different secondary-structure elements.
PMID- 25849404
TI - Time-lapse anomalous X-ray diffraction shows how Fe(2+) substrate ions move
through ferritin protein nanocages to oxidoreductase sites.
AB - Ferritin superfamily protein cages reversibly synthesize internal biominerals,
Fe2O3.H2O. Fe(2+) and O2 (or H2O2) substrates bind at oxidoreductase sites in the
cage, initiating biomineral synthesis to concentrate iron and prevent potentially
toxic reactions products from Fe(2+)and O2 or H2O2 chemistry. By freezing
ferritin crystals of Rana catesbeiana ferritin M (RcMf) at different time
intervals after exposure to a ferrous salt, a series of high-resolution anomalous
X-ray diffraction data sets were obtained that led to crystal structures that
allowed the direct observation of ferrous ions entering, moving along and binding
at enzyme sites in the protein cages. The ensemble of crystal structures from
both aerobic and anaerobic conditions provides snapshots of the iron substrate
bound at different cage locations that vary with time. The observed differential
occupation of the two iron sites in the enzyme oxidoreductase centre (with Glu23
and Glu58, and with Glu58, His61 and Glu103 as ligands, respectively) and other
iron-binding sites (with Glu53, His54, Glu57, Glu136 and Asp140 as ligands)
reflects the approach of the Fe(2+) substrate and its progression before the
enzymatic cycle 2Fe(2+) + O2 -> Fe(3+)-O-O-Fe(3+) -> Fe(3+)-O(H)-Fe(3+) and
turnover. The crystal structures also revealed different Fe(2+) coordination
compounds bound to the ion channels located at the threefold and fourfold
symmetry axes of the cage.
PMID- 25849407
TI - Structural and functional characterization of TesB from Yersinia pestis reveals a
unique octameric arrangement of hotdog domains.
AB - Acyl-CoA thioesterases catalyse the hydrolysis of the thioester bonds present
within a wide range of acyl-CoA substrates, releasing free CoASH and the
corresponding fatty-acyl conjugate. The TesB-type thioesterases are members of
the TE4 thioesterase family, one of 25 thioesterase enzyme families characterized
to date, and contain two fused hotdog domains in both prokaryote and eukaryote
homologues. Only two structures have been elucidated within this enzyme family,
and much of the current understanding of the TesB thioesterases has been based on
the Escherichia coli structure. Yersinia pestis, a highly virulent bacterium,
encodes only one TesB-type thioesterase in its genome; here, the structural and
functional characterization of this enzyme are reported, revealing unique
elements both within the protomer and quaternary arrangements of the hotdog
domains which have not been reported previously in any thioesterase family. The
quaternary structure, confirmed using a range of structural and biophysical
techniques including crystallography, small-angle X-ray scattering, analytical
ultracentrifugation and size-exclusion chromatography, exhibits a unique
octameric arrangement of hotdog domains. Interestingly, the same biological unit
appears to be present in both TesB structures solved to date, and is likely to be
a conserved and distinguishing feature of TesB-type thioesterases. Analysis of
the Y. pestis TesB thioesterase activity revealed a strong preference for
octanoyl-CoA and this is supported by structural analysis of the active site.
Overall, the results provide novel insights into the structure of TesB
thioesterases which are likely to be conserved and distinguishing features of the
TE4 thioesterase family.
PMID- 25849406
TI - Combination of X-ray crystallography, SAXS and DEER to obtain the structure of
the FnIII-3,4 domains of integrin alpha6beta4.
AB - Integrin alpha6beta4 is a major component of hemidesmosomes that mediate the
stable anchorage of epithelial cells to the underlying basement membrane.
Integrin alpha6beta4 has also been implicated in cell proliferation and migration
and in carcinoma progression. The third and fourth fibronectin type III domains
(FnIII-3,4) of integrin beta4 mediate binding to the hemidesmosomal proteins
BPAG1e and BPAG2, and participate in signalling. Here, it is demonstrated that X
ray crystallography, small-angle X-ray scattering and double electron-electron
resonance (DEER) complement each other to solve the structure of the FnIII-3,4
region. The crystal structures of the individual FnIII-3 and FnIII-4 domains were
solved and the relative arrangement of the FnIII domains was elucidated by
combining DEER with site-directed spin labelling. Multiple structures of the
interdomain linker were modelled by Monte Carlo methods complying with DEER
constraints, and the final structures were selected against experimental
scattering data. FnIII-3,4 has a compact and cambered flat structure with an
evolutionary conserved surface that is likely to correspond to a protein
interaction site. Finally, this hybrid method is of general application for the
study of other macromolecules and complexes.
PMID- 25849408
TI - The role of monovalent cations in the ATPase reaction of DNA gyrase.
AB - Four new crystal structures of the ATPase domain of the GyrB subunit of
Escherichia coli DNA gyrase have been determined. One of these, solved in the
presence of K(+), is the highest resolution structure reported so far for this
domain and, in conjunction with the three other structures, reveals new insights
into the function of this domain. Evidence is provided for the existence of two
monovalent cation-binding sites: site 1, which preferentially binds a K(+) ion
that interacts directly with the alpha-phosphate of ATP, and site 2, which
preferentially binds an Na(+) ion and the functional significance of which is not
clear. The crystallographic data are corroborated by ATPase data, and the
structures are compared with those of homologues to investigate the broader
conservation of these sites.
PMID- 25849410
TI - Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid
binding SCP/TAPS protein that lacks the prototypical CAP motifs. Corrigendum.
PMID- 25849411
TI - Food colors: Existing and emerging food safety concerns.
AB - Food colors are added to different types of commodities to increase their visual
attractiveness or to compensate for natural color variations. The use of these
additives is strictly regulated in the European Union, the United States, and
many other countries worldwide. There is a growing concern about the safety of
some commonly used legal food colorants and there is a trend to replace the
synthetic forms with natural products. Additionally, a number of dyes with known
or suspected genotoxic or carcinogenic properties have been shown to be added
illegally to foods. Robust monitoring programs based on reliable detection
methods are required to assure the food is free from harmful colors. The aim of
this review is to present an up to date status of the various concerns arising
from use of color additives in food. The most important food safety concerns in
the field of food colors are lack of uniform regulation concerning legal food
colors worldwide, possible link of artificial colors to hyperactive behavior,
replacement of synthetic colors with natural ones, and the presence of harmful
illegal dyes-both known but also new, emerging ones in food. The legal status of
food color additives in the EU, United States, and worldwide is summarized. The
reported negative health effects of both legal and illegal colors are presented.
The European Rapid Alert System for Food and Feed notifications and US import
alerts concerning food colors are analyzed and trends in fraudulent use of color
additives identified. The detection methods for synthetic colors are also
reviewed.
PMID- 25849409
TI - Structures of the hydrolase domain of zebrafish 10-formyltetrahydrofolate
dehydrogenase and its complexes reveal a complete set of key residues for
hydrolysis and product inhibition.
AB - 10-Formyltetrahydrofolate dehydrogenase (FDH), which is composed of a small N
terminal domain (Nt-FDH) and a large C-terminal domain, is an abundant folate
enzyme in the liver and converts 10-formyltetrahydrofolate (10-FTHF) to
tetrahydrofolate (THF) and CO2. Nt-FDH alone possesses a hydrolase activity,
which converts 10-FTHF to THF and formate in the presence of beta
mercaptoethanol. To elucidate the catalytic mechanism of Nt-FDH, crystal
structures of apo-form zNt-FDH from zebrafish and its complexes with the
substrate analogue 10-formyl-5,8-dideazafolate (10-FDDF) and with the products
THF and formate have been determined. The structures reveal that the
conformations of three loops (residues 86-90, 135-143 and 200-203) are altered
upon ligand (10-FDDF or THF) binding in the active site. The orientations and
geometries of key residues, including Phe89, His106, Arg114, Asp142 and Tyr200,
are adjusted for substrate binding and product release during catalysis. Among
them, Tyr200 is especially crucial for product release. An additional potential
THF binding site is identified in the cavity between two zNt-FDH molecules, which
might contribute to the properties of product inhibition and THF storage reported
for FDH. Together with mutagenesis studies and activity assays, the structures of
zNt-FDH and its complexes provide a coherent picture of the active site and a
potential THF binding site of zNt-FDH along with the substrate and product
specificity, lending new insights into the molecular mechanism underlying the
enzymatic properties of Nt-FDH.
PMID- 25849413
TI - Laboratory- and Field-Based Assessment of Maximal Aerobic Power of Elite Stand-Up
Paddle-Board Athletes.
AB - PURPOSE: Stand-up paddle boarding (SUP) is a rapidly growing sport and
recreational activity for which only anecdotal evidence exists on its proposed
health, fitness, and injury-rehabilitation benefits. PARTICIPANTS: 10
internationally and nationally ranked elite SUP athletes. METHODS: Participants
were assessed for their maximal aerobic power on an ergometer in a laboratory and
compared with other water-based athletes. Field-based assessments were
subsequently performed using a portable gas-analysis system, and a correlation
between the 2 measures was performed. RESULTS: Maximal aerobic power (relative)
was significantly higher (P = .037) when measured in the field with a portable
gas-analysis system (45.48 +/- 6.96 mL . kg(-1) . min(-1)) than with laboratory
based metabolic-cart measurements (43.20 +/- 6.67 mL . kg(-1) . min(-1)). There
was a strong, positive correlation (r = .907) between laboratory and field
maximal aerobic power results. Significantly higher (P = .000) measures of SUP
paddling speed were found in the field than with the laboratory ergometer
(+42.39%). There were no significant differences in maximal heart rate between
the laboratory and field settings (P = .576). CONCLUSION: The results demonstrate
the maximal aerobic power representative of internationally and nationally ranked
SUP athletes and show that SUP athletes can be assessed for maximal aerobic power
in the laboratory with high correlation to field-based measures. The field-based
portable gas-analysis unit has a tendency to consistently measure higher oxygen
consumption. Elite SUP athletes display aerobic power outputs similar to those of
other upper-limb-dominant elite water-based athletes (surfing, dragon-boat
racing, and canoeing).
PMID- 25849412
TI - The role of polymerase chain reaction of high-risk human papilloma virus in the
screening of high-grade squamous intraepithelial lesions in the anal mucosa of
human immunodeficiency virus-positive males having sex with males.
AB - OBJECTIVES: To evaluate the advantages of cytology and PCR of high-risk human
papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade
squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having
sex with men (MSM). METHODS: This is a single-centered study conducted between
May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our
outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for
PCR HPV analysis and for cytology. Anoscopy was performed for histology
evaluation. RESULTS: Anoscopy showed 33.8% were normal, 47.8% low-grade squamous
intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV
had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening,
with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9
and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity
and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was,
generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or
low (<0.4). Area under the receiver operating characteristics (AUROC) curve
analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6).
Multivariate regression analysis showed protective factors against HSIL were:
viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR:
0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR:
20.1; 95%CI: 2.04-197.82). CONCLUSIONS: When cytology and PCR HR-HPV findings are
normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV
suppression with treatment protects against the appearance of HSIL [corrected].
PMID- 25849414
TI - Palladium(II)-catalyzed intramolecular carboxypalladation-olefin insertion
cascade: direct access to indeno[1,2-b]furan-2-ones.
AB - A catalytic, atom-economical, domino 5-endo-dig cyclization-intramolecular olefin
insertion sequence was developed under mild conditions. Aryl alkynoic acids
bearing a tethered enone partner afforded the indeno[1,2-b]furan-2-ones, the core
skeleton present in a number of biologically significant molecules including the
natural product solanacol, under ligand-free, palladium-catalyzed reaction
conditions in high yields. The competitive beta-hydride elimination in the final
step leading to the conjugated analogs was avoided by the addition of lithium
bromide. A plausible mechanism for this domino sequence is proposed involving
intramolecular carboxypalladation and olefin insertion steps.
PMID- 25849415
TI - The effects of static stretching on speed and agility: One or multiple repetition
protocols?
AB - Although static stretching (SS) is utilized during warm-up before training and
competition, the results about its effects on performance remain controversial.
We examined whether performing a stretch of short-to-moderate duration (<60 sec)
in a single repetition produces a similar or different effect on speed and
agility performance from the effect which is produced while performing the same
stretch in multiple repetitions of the same total duration. According to a
repeated measurement design, 40 trained males were randomly assigned to either
(1) a single repetition group or (2) a multiple repetition group. The
participants in each group performed five trials: a control trial (no stretches
were performed) and four experimental trials of SS protocols consisting of five
exercises performed at either 20 sec (2 * 10 in the second group), 30 sec (3 * 10
in the second group), 40 sec (4 * 10 in the second group) or 60 sec (6 * 10 in
the second group) of total duration. A two-way repeated measures analysis of
variance showed that the participants in both group improved their speed
performance in response to the 20-sec trial, whereas agility remained unaffected.
Data analysis also revealed that the repetition number did not affect speed and
agility performance. These data suggest that SS of short duration (<30 sec) may
actually improve acute speed performance, whereas SS of moderate duration may not
hamper speed and agility performance. Moreover, the effects of SS protocols are
related to the total duration of each exercise and not to the number of
repetitions in which each exercise is performed.
PMID- 25849417
TI - Unconventional actins and actin-binding proteins in human protozoan parasites.
AB - Actin and its regulatory proteins play a key role in several essential cellular
processes such as cell movement, intracellular trafficking and cytokinesis in
most eukaryotes. While these proteins are highly conserved in higher eukaryotes,
a number of unicellular eukaryotic organisms contain divergent forms of these
proteins which have highly unusual biochemical and structural properties. Here,
we review the biochemical and structural properties of these unconventional
actins and their core binding proteins which are present in commonly occurring
human protozoan parasites.
PMID- 25849416
TI - Burden of invasive group B Streptococcus disease and early neurological sequelae
in South African infants.
AB - INTRODUCTION: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis
and meningitis. We aimed to evaluate the burden of invasive early-onset (0-6 days
of life, EOD) and late-onset (7-89 days, LOD) GBS disease and subsequent
neurological sequelae in infants from a setting with a high prevalence (29.5%) of
HIV among pregnant women. METHODS: A case-control study was undertaken at three
secondary-tertiary care public hospitals in Johannesburg. Invasive cases in
infants <3 months age were identified by surveillance of laboratories from
November 2012 to February 2014. Neurodevelopmental screening was done in
surviving cases and controls at 3 and 6 months of age. RESULTS: We identified 122
cases of invasive GBS disease over a 12 month period. Although the incidence (per
1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed
infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24-9.74)
greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall,
serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD,
respectively. Risk factors for EOD included offensive draining liquor (adjusted
Odds Ratio: 27.37; 95%CI: 1.94-386.50) and maternal GBS bacteriuria (aOR: 8.41;
95%CI: 1.44-49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17
10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds
for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44-120.95)
greater in cases (13.2%) than controls (0.4%). DISCUSSION: The high burden of
invasive GBS disease in South Africa, which is also associated with high case
fatality rates and significant neurological sequelae among survivors, is partly
due to the heightened risk for LOD in infants born to HIV-infected women. An
effective trivalent GBS conjugate vaccine targeted at pregnant women could
prevent invasive GBS disease in this setting.
PMID- 25849418
TI - Mitochondrial carnitine/acylcarnitine transporter, a novel target of mercury
toxicity.
AB - The effect of Hg(2+) and CH3Hg(+) on the mitochondrial carnitine/acylcarnitine
transporter (CACT) has been studied on the recombinant protein and on the CACT
extracted from HeLa cells or Zebrafish and reconstituted in proteoliposomes.
Transport was abolished upon treatment of the recombinant CACT in proteoliposomes
by Hg(2+) or CH3Hg(+). Inhibition was reversed by the SH reducing agent 1,4
dithioerythritol, GSH, and N-acetylcysteine. IC50 for Hg(2+) and CH3Hg(+) of 90
nM and 137 nM, respectively, were measured by dose-response analyses. Inhibition
was abolished in the C-less CACT mutant. Strong reduction of inhibition by both
reagents was observed in the C136A and some reduction in the C155A mutants.
Inhibition similar to that of the WT was observed in the
C23V/C58V/C89S/C155V/C283S mutant, containing only C136. Optimal inhibition by
Hg(2+)was found in the four replacement mutants C23V/C58V/C89S/C283S containing
both C136 and C155 indicating cross-reaction of Hg(2+) with the two Cys residues.
Inhibition kinetic analysis showed mixed inhibition by Hg(2+) or competitive
inhibition by CH3Hg(+). HeLa cells or Zebrafish were treated with the more potent
inhibitor. Ten micromolar HgCl2 caused clear impairment of viability of HeLa
cells. The transport assay in proteoliposomes with CACT extracted from treated
cells showed that the transporter was inactivated and that DTE rescued the
activity. Nearly identical results were observed with Zebrafish upon extraction
of the CACT from the liver of the treated animals that, indeed, showed
accumulation of the mercurial compound.
PMID- 25849419
TI - From the impact factor to DORA and the scientific content of articles.
PMID- 25849422
TI - In vivo secretion of anti-CD3 * anti-tumor bispecific antibodies by gene-modified
cells: over a decade of T-cell engagement.
PMID- 25849423
TI - Transduction of antigen-presenting cells in the brain by AAV9 warrants caution in
preclinical studies.
PMID- 25849424
TI - Response to "in vivo secretion of anti-CD3 * anti-tumor bispecific antibodies by
gene-modified cells: over a decade of T-cell engagement".
PMID- 25849425
TI - A shot in the bone corrects a genetic disease.
PMID- 25849427
TI - Corrigendum to "CD133-targeted gene transfer into long-term repopulating
hematopoietic stem cells".
PMID- 25849426
TI - Antiobesity strategy targets energy economy safeguards.
PMID- 25849428
TI - Corrigendum to "let-7 microRNAs regenerate peripheral nerve regeneration by
targeting nerve growth factor".
PMID- 25849429
TI - Reconstructible phylogenetic networks: do not distinguish the indistinguishable.
AB - Phylogenetic networks represent the evolution of organisms that have undergone
reticulate events, such as recombination, hybrid speciation or lateral gene
transfer. An important way to interpret a phylogenetic network is in terms of the
trees it displays, which represent all the possible histories of the characters
carried by the organisms in the network. Interestingly, however, different
networks may display exactly the same set of trees, an observation that poses a
problem for network reconstruction: from the perspective of many inference
methods such networks are "indistinguishable". This is true for all methods that
evaluate a phylogenetic network solely on the basis of how well the displayed
trees fit the available data, including all methods based on input data
consisting of clades, triples, quartets, or trees with any number of taxa, and
also sequence-based approaches such as popular formalisations of maximum
parsimony and maximum likelihood for networks. This identifiability problem is
partially solved by accounting for branch lengths, although this merely reduces
the frequency of the problem. Here we propose that network inference methods
should only attempt to reconstruct what they can uniquely identify. To this end,
we introduce a novel definition of what constitutes a uniquely reconstructible
network. For any given set of indistinguishable networks, we define a canonical
network that, under mild assumptions, is unique and thus representative of the
entire set. Given data that underwent reticulate evolution, only the canonical
form of the underlying phylogenetic network can be uniquely reconstructed. While
on the methodological side this will imply a drastic reduction of the solution
space in network inference, for the study of reticulate evolution this is a
fundamental limitation that will require an important change of perspective when
interpreting phylogenetic networks.
PMID- 25849431
TI - Correction: genetic dissection of photoperiod response based on GWAS of pre
anthesis phase duration in spring barley.
PMID- 25849430
TI - Suppression of Escherichia coli O157:H7 by Dung Beetles (Coleoptera:
Scarabaeidae) using the lowbush blueberry agroecosystem as a model system.
AB - Wildlife as a source of microbial contamination is a food safety concern. Deer
feces (scat) have been determined as a point source for Escherichia coli O157:H7
contamination of fresh produce. The ecological role of the scooped scarab
(Onthophagus hecate (Panzer)), a generalist dung beetle species common in Maine
blueberry fields, was explored as a biological control agent and alternatively as
a pathogen vector between deer scat and food. A large-scale field survey of
wildlife scat indicated that pathogenic E. coli O157:H7 was present, albeit at a
low prevalence (1.9% of samples, n = 318), in the Maine lowbush blueberry
agroecosystem. A manipulative field experiment verified that, should contact
occur between deer scat and blueberry plants and fruit during the summer,
contamination with E. coli O157:H7 can occur and persist for more than 72 h. For
both the positive control and an experimental scat inoculation treatment, the
levels of the bacterial population decreased over time, but at different rates
(treatment x time interaction: F (1.9,18.8) = 358.486, P < 0.0001). The positive
control inoculation, which resulted in a higher initial E. coli level on fruit,
decayed at a faster rate than inoculation of fruit via scat in the experimental
treatment. We conducted 2 laboratory studies to elucidate aspects of dung beetle
feeding ecology as it relates to suppression of E. coli O157:H7 from deer scat to
lowbush blueberry fruit. In both experiments, dung beetles buried the same amount
of scat whether or not the scat was inoculated with the pathogen (F(1,6) = 0.001;
P = 0.999 and (F (2,17) = 4.10, P = 0.147). Beetles feeding on E. coli inoculated
deer scat were not found to vector the pathogen to fruit. In two studies, beetles
lowered the amount of pathogenic E. coli persisting in soils compared to soils
without beetles (F (2,9) = 7.757; P = 0.05 and F (2,17) = 8.0621, P = 0.004). Our
study suggests that the dung beetle species, Onthophagus hecate, has the
potential to contribute to the suppression of E. coli O157:H7 in agricultural
landscapes.
PMID- 25849432
TI - Propofol post-conditioning protects the blood brain barrier by decreasing matrix
metalloproteinase-9 and aquaporin-4 expression and improves the neurobehavioral
outcome in a rat model of focal cerebral ischemia-reperfusion injury.
AB - Propofol, an intravenous anesthetic, inhibits neuronal apoptosis induced by
ischemic stroke, protects the brain from ischemia/reperfusion injury and improves
neuronal function. However, whether propofol is able to protect the blood brain
barrier (BBB) and the underlying mechanisms have remained to be elucidated. In
the present study, a rat model of cerebral ischemia/reperfusion was established,
using a thread embolism to achieve middle cerebral artery occlusion. Rats were
treated with propofol (propofol post-conditioning) or physiological saline
(control) administered by intravenous injection 30 min following reperfusion.
Twenty-four hours following reperfusion, neurobehavioral manifestations were
assessed. The levels of cephaloedema, damage to the BBB and expression levels of
matrix metalloproteinase-9 (MMP-9), aquaporin-4 (AQP-4) and phosphorylated c-Jun
N-terminal kinase (pJNK) were determined in order to evaluate the effects of
propofol on the BBB. In comparison to the cerebral ischemia/reperfusion group,
the levels of brain water content and Evans blue content, as well as the
expression levels of MMP-9, AQP-4 and pJNK were significantly reduced in the
propofol post-conditioning group. These results indicated that propofol post
conditioning improved the neurobehavioral manifestations and attenuated the BBB
damage and cephaloedema induced following cerebral ischemia/reperfusion. This
effect may be due to the inhibition of MMP-9 and AQP-4 expression, and the
concurrent decrease in JNK phosphorylation.
PMID- 25849433
TI - Improving men's participation in preventing mother-to-child transmission of HIV
as a maternal, neonatal, and child health priority in South Africa.
PMID- 25849434
TI - Women in "Sexual" Pain: Exploring the Manifestations of Vulvodynia.
AB - This study explored the sexual and pain histories and pain presentations of women
with forms of chronic vulvar pain (i.e., vulvodynia). One hundred and seventy
seven women with five subtypes of vulvodynia completed an online questionnaire.
Groups were similar across several domains: participants experienced pain for
many years during sexual and nonsexual activities, and pain was rated as moderate
to severe. However, several differences emerged when considering pain
development, number of sexual partners, and treatment seeking. This study
illustrates how severe vulvodynia pain can be, regardless of subtype. However,
not all vulvodynia sufferers are alike, and distinctions between research and
clinical practice are highlighted.
PMID- 25849436
TI - TGF-beta1 induced transdifferentiation of rpe cells is mediated by TAK1.
AB - BACKGROUND AND AIM: Proliferative vitreoretinopathy (PVR) is an active process
that develops as a complication upon retinal detachment (RD), accompanied by
formation of fibrotic tissue. The main cells involved in the development of
fibrotic tissue during PVR are the retinal pigment epithelial (RPE) cells. The
RPE cells undergo epithelial-mesenchymal transition (EMT) which leads to complex
retinal detachment and loss of vision. Transforming growth factor-beta1 (TGF
beta1) is considered as the main player in the EMT of RPE cells, even though the
mechanism is not fully understood. This study was performed to determine the
possible involvement of transforming growth factor beta activated kinase 1 (TAK1)
in the EMT process of the RPE cells. METHODOLOGY: ARPE-19 Cells were treated with
5Z-7 oxozeaenol (TAK1 inhibitor) or SB431542 (TGF-beta1 receptor kinase
inhibitor) followed by TGF-beta1 stimulation. Immunofluorescence, scratch assay
Real time PCR and collagen contraction assay assessed the EMT features. The
phosphorylation of Smad2/3 and p38 was examined using western blots analysis.
RESULTS: This study demonstrates that stimulation of RPE cells with TGF-beta1
increases alpha-SMA expression, cell migration and cell contractility, all of
which are EMT features. Remarkably, addition of TAK1 inhibitor abolishes all
these processes. Furthermore, we show hereby that TAK1 regulates not only the
activation of the non-canonical cascade of TGF-beta1 (p38), but also the
canonical cascade, the Smad2/3 activation. Thus, the outcome of the TGF-beta
response in RPE cells is TAK1 dependent. CONCLUSIONS/SIGNIFICANCE: This work
demonstrated TAK1, a component of the non-canonical pathway of TGF-beta1, is a
key player in the EMT process, thus provides deep insight into the pathogenesis
of PVR. The ability to halt the process of EMT in RPE cells may reduce the
severity of the fibrotic response that occurs upon PVR, leading to a better
prognosis and increase the probability of success in RD treatment.
PMID- 25849437
TI - Comprehensive analysis of maillard protein modifications in human lenses: effect
of age and cataract.
AB - In human lens proteins, advanced glycation endproducts (AGEs) originate from the
reaction of glycating agents, e.g., vitamin C and glucose. AGEs have been
considered to play a significant role in lens aging and cataract formation.
Although several AGEs have been detected in the human lens, the contribution of
individual glycating agents to their formation remains unclear. A highly
sensitive liquid chromatography-tandem mass spectrometry multimethod was
developed that allowed us to quantitate 21 protein modifications in normal and
cataractous lenses, respectively. N(6)-Carboxymethyl lysine, N(6)-carboxyethyl
lysine, N(7)-carboxyethyl arginine, methylglyoxal hydroimidazolone 1, and N(6)
lactoyl lysine were found to be the major Maillard protein modifications among
these AGEs. The novel vitamin C specific amide AGEs, N(6)-xylonyl and N(6)
lyxonyl lysine, but also AGEs from glyoxal were detected, albeit in minor
quantities. Among the 21 modifications, AGEs from the Amadori product (derived
from the reaction of glucose and lysine) and methylglyoxal were dominant.
PMID- 25849438
TI - Drug therapy for patients with systolic heart failure after the PARADIGM-HF
trial: in need of a new paradigm of LCZ696 implementation in clinical practice.
AB - Heart failure represents a primary cause of morbidity and mortality in older
people and despite significant therapeutic advances, it is still characterized by
important unmet needs, thus remaining a challenging field of clinical research.
The recent PARADIGM-HF trial compared the novel compound LCZ696, a combination of
the angiotensin receptor blocker valsartan and the neprilysin inhibitor
sacubitril, versus the angiotensin-converting enzyme inhibitor enalapril in 8,442
patients with symptomatic chronic systolic heart failure. LCZ696 led to a 20%
reduction in the rate of death or hospitalization for heart failure and a 16%
reduction in the rate of all-cause death compared to enalapril at 3.5 years of
follow-up. Despite those impressive results, the clinical application of this
novel agent that requires the substitution of a cornerstone of current heart
failure therapy, the angiotensin-converting enzyme inhibitors, should follow
careful steps as imposed by the study design, the recruited population and the
outcome in specific patient subgroups. Further insights into the effects of
LCZ696 will be provided by the ongoing PARAGON-HF trial in patients with
diastolic heart failure.
PMID- 25849439
TI - Regulation of Apoptotic Endonucleases by EndoG.
AB - Cells contain several apoptotic endonucleases, which appear to act simultaneously
before and after cell death by destroying the host cell DNA. It is largely
unknown how the endonucleases are being induced and whether they can regulate
each other. This study was performed to determine whether apoptotic mitochondrial
endonuclease G (EndoG) can regulate expression of other apoptotic endonucleases.
The study showed that overexpression of mature EndoG in kidney tubular epithelial
NRK-52E cells can increase expression of caspase-activated DNase (CAD) and four
endonucleases that belong to DNase I group including DNase I, DNase X, DNase IL2,
and DNase gamma, but not endonucleases of the DNase 2 group. The induction of
DNase I-type endonucleases was associated with DNA degradation in promoter/exon 1
regions of the endonuclease genes. These results together with findings on
colocalization of immunostained endonucleases and TUNEL suggest that DNA
fragmentation after EndoG overexpression was caused by DNase I endonucleases and
CAD in addition to EndoG itself. Overall, these data provide first evidence for
the existence of the integral network of apoptotic endonucleases regulated by
EndoG.
PMID- 25849440
TI - Incidence and risk factors for neonatal tetanus in admissions to Kilifi County
Hospital, Kenya.
AB - BACKGROUND: Neonatal Tetanus (NT) is a preventable cause of mortality and
neurological sequelae that occurs at higher incidence in resource-poor countries,
presumably because of low maternal immunisation rates and unhygienic cord care
practices. We aimed to determine changes in the incidence of NT, characterize and
investigate the associated risk factors and mortality in a prospective cohort
study including all admissions over a 15-year period at a County hospital on the
Kenyan coast, a region with relatively high historical NT rates within Kenya.
METHODS: We assessed all neonatal admissions to Kilifi County Hospital in Kenya
(1999-2013) and identified cases of NT (standard clinical case definition)
admitted during this time. Poisson regression was used to examine change in
incidence of NT using accurate denominator data from an area of active
demographic surveillance. Logistic regression was used to investigate the risk
factors for NT and factors associated with mortality in NT amongst neonatal
admissions. A subset of sera from mothers (n = 61) and neonates (n = 47) were
tested for anti-tetanus antibodies. RESULTS: There were 191 NT admissions, of
whom 187 (98%) were home deliveries. Incidence of NT declined significantly
(Incidence Rate Ratio: 0.85 (95% Confidence interval 0.81-0.89), P<0.001) but the
case fatality (62%) did not change over the study period (P = 0.536). Younger
infant age at admission (P = 0.001) was the only independent predictor of
mortality. Compared to neonatal hospital admittee controls, the proportion of
home births was higher among the cases. Sera tested for antitetanus antibodies
showed most mothers (50/61, 82%) had undetectable levels of antitetanus
antibodies, and most (8/9, 89%) mothers with detectable antibodies had a neonate
without protective levels. CONCLUSIONS: Incidence of NT in Kilifi County has
significantly reduced, with reductions following immunisation campaigns. Our
results suggest immunisation efforts are effective if sustained and efforts
should continue to expand coverage.
PMID- 25849441
TI - The application of multiplex fluorimetric sensor for the analysis of flavonoids
content in the medicinal herbs family Asteraceae, Lamiaceae, Rosaceae.
AB - BACKGROUND: The aim of our research work was to quantify total flavonoid contents
in the leaves of 13 plant species family Asteraceae, 8 representatives of family
Lamiaceae and 9 plant species belonging to family Rosaceae, using the multiplex
fluorimetric sensor. Fluorescence was measured using optical fluorescence
apparatus Multiplex(R) 3 (Force-A, France) for non-destructive flavonoids
estimation. The content of total flavonoids was estimated by FLAV index
(expressed in relative units), that is deduced from flavonoids UV absorbing
properties. RESULTS: Among observed plant species, the highest amount of total
flavonoids has been found in leaves of Helianthus multiflorus (1.65 RU) and
Echinops ritro (1.27 RU), Rudbeckia fulgida (1.13 RU) belonging to the family
Asteraceae. Lowest flavonoid content has been observed in the leaves of marigold
(Calendula officinalis) (0.14 RU) also belonging to family Asteraceae. The
highest content of flavonoids among experimental plants of family Rosaceae has
been estimated in the leaves of Rosa canina (1.18 RU) and among plant species of
family Lamiaceae in the leaves of Coleus blumei (0.90 RU). CONCLUSIONS: This
research work was done as pre-screening of flavonoids content in the leaves of
plant species belonging to family Asteraceae, Lamiaceae and Rosaceae. Results
indicated that statistically significant differences (P > 0.05) in flavonoids
content were observed not only between families, but also among individual plant
species within one family.
PMID- 25849442
TI - A versatile technology for droplet-based microfluidics: thermomechanical
actuation.
AB - We report on a versatile technique for microfluidic droplet manipulation that
proves effective at every step: from droplet generation to propulsion to sorting,
rearrangement or break-up. Non-wetting droplets are thermomechanically actuated
in a microfluidic chip using local heating resistors. Controlled temperature
variation induces local dilation of the PDMS wall above the resistor, which
drives the droplet away from the hot (i.e. constricted) region (B. Selva, I.
Cantat and M.-C. Jullien, Phys. Fluids, 2011, 23, 052002). Adapted placing and
actuation of such resistors thus allow us to push forward, stop, store and
release, or even break up droplets, at the price of low electric power
consumption (<150 mW). We believe this technically accessible method to provide a
useful tool for droplet microfluidics.
PMID- 25849444
TI - Regioselectivity in the Au-catalyzed hydration and hydroalkoxylation of alkynes.
AB - Over the past decade and a half, homogenous gold catalysis has emerged as a
diverse and rich field of research resulting in the continuous development of new
methods for organic synthesis. The activation of alkynes towards nucleophilic
attack by Au(I) and Au(III) complexes is a well-established mode of reactivity
and the gold-catalyzed hydration and hydroalkoxylation of alkynes are two of the
more well-explored reaction pathways. Although these classes of reactions have
seen continuous development since their initial reports, achieving
regioselectivity persists as one of the most challenging issues for this
chemistry. This article aims to draw attention to the general problem of
regioselectivity in these reactions. A select set of examples is presented to
highlight the challenges and survey some of the strategies employed to address
this problem.
PMID- 25849445
TI - Mechanism of rhodium-catalyzed cyclopropanation/cyclization of allenynes.
AB - The rhodium-catalyzed cyclopropanation/cyclization of allenynes was investigated
by means of DFT calculations. The results show that the cyclopropanation via the
proposed stepwise C(sp(3))-H activation (sigma-bond metathesis/C-H reductive
elimination) was kinetically unfavorable. Instead, a concerted C(sp(3))-H
activation pathway, namely the metal-assisted sigma-bond metathesis, in which the
hydrogen was directly transferred to the rhodacyclopentane assisted by the Rh
center followed by a C-C reductive elimination, was found to explain the
experimental results.
PMID- 25849443
TI - The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: implications
for developing new model organisms.
AB - Nuclear receptors (NRs) are transcription regulators involved in an array of
diverse physiological functions including key roles in endocrine and metabolic
function. The aim of this study was to identify nuclear receptors in the fully
sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host
for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to
assessing the snail's potential as a invertebrate model organism for endocrine
function, both as a prospective new test organism and to elucidate the
fundamental genetic and mechanistic causes of disease. For comparative purposes,
the genome of a second gastropod, the owl limpet, Lottia gigantea was also
investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs
were identified from the B. glabrata and L. gigantea genomes respectively, based
on the presence of a conserved DNA-binding domain and/or ligand-binding domain.
Nuclear receptor transcript expression was confirmed and sequences were subjected
to a comparative phylogenetic analysis, which demonstrated that these molluscs
have representatives of all the major NR subfamilies (1-6). Many of the
identified NRs are conserved between vertebrates and invertebrates, however
differences exist, most notably, the absence of receptors of Group 3C, which
includes some of the vertebrate endocrine hormone targets. The mollusc genomes
also contain NR homologues that are present in insects and nematodes but not in
vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many
shared receptors between humans and molluscs indicates the potential for molluscs
as model organisms; however the absence of several steroid hormone receptors
indicates snail endocrine systems are fundamentally different.
PMID- 25849446
TI - Correction: one-step multiplex PCR assay for detecting Streptococcus pneumoniae
serogroups/types covered by 13-valent pneumococcal conjugate vaccine (PCV13).
PMID- 25849447
TI - Correction to Imidazol-1-ylethylindazole Voltage-Gated Sodium Channel Ligands Are
Neuroprotective during Optic Neuritis in a Mouse Model of Multiple Sclerosis.
PMID- 25849448
TI - Breast cancer or metastasis? An unusual case of metastatic malignant pleural
mesothelioma to the breast.
AB - BACKGROUND: Metastases to the breast from extramammary malignancies are very
rare, and ruling out the diagnosis of primary breast tumor is important in order
to decide on clinical management and predict prognosis. CASE PRESENTATION:
Clinical examination revealed in a 49-year-old hairdresser a 3-cm hard lump
adherent to the underlying layers in the right breast. Trucut biopsy was
performed. Histology showed a solid proliferation of medium-sized neoplastic
polygonal cells. Immunohistochemical analysis showed tumor cells diffusely
positive for cytokeratin 8/18 and calretinin and focally positive for cytokeratin
5/6 and Wilms' tumor 1, e-cadherin, and human bone marrow endothelial-1. Estrogen
receptors and progesterone receptors were negative. The final diagnosis was
metastatic epithelioid malignant pleural mesothelioma. CONCLUSIONS:
Immunohistochemistry is an important tool for a conclusive diagnosis of malignant
pleural mesothelioma. Owing to the degree of histological and immunohistochemical
overlap, a high level of clinical suspicion is essential in order to avoid
unnecessary mutilating surgery.
PMID- 25849449
TI - Threshold Photoelectron Spectra of Combustion Relevant C4H5 and C4H7 Isomers.
AB - Threshold photoelectron spectra of combustion relevant C4H5 isomers, 2-butyn-1-yl
and 1-butyn-3-yl, and C4H7 isomers, 1-methylallyl and 2-methylallyl, have been
recorded using vacuum ultraviolet synchrotron radiation. Adiabatic ionization
energies (IEad) have been determined by assigning spectroscopic transitions in
mass-selected threshold photoelectron spectra aided by Franck-Condon simulations.
The following values were obtained: (7.97 +/- 0.02) eV (1-butyn-3-yl), (7.94 +/-
0.02) eV (2-butyn-1-yl), (7.48 +/- 0.01) eV (1-E-methylallyl), (7.59 +/- 0.01) eV
(1-Z-methylallyl), and (7.88 +/- 0.01) eV (2-methylallyl). Good agreement with
CBS-QB3 calculations and simulations could be achieved.
PMID- 25849451
TI - Effectiveness of a pilot partner notification program for new HIV cases in
Barcelona, Spain.
AB - BACKGROUND: An estimated 30% of HIV cases in the European Union are not aware of
their serological status. This study aimed to assess the effectiveness of a pilot
HIV partner notification program. METHODS: HIV cases diagnosed between January
2012 and June 2013 at two healthcare settings in Barcelona were invited to
participate in a prospective survey. We identified process and outcome measures
to evaluate this partner notification program, including the number of partners
identified per interviewed index case, the proportion of partners tested for HIV
as a result of the partner notification, and the proportion of new HIV diagnoses
among their sex or needle-sharing partners. RESULTS: Of the 125 index cases
contacted, 108 (86.4%) agreed to provide information about partners. A total of
199 sexual partners were identified (1.8 partners per interviewed index case).
HIV outcome was already known for 58 partners (70.7% were known to be HIV
positive), 141 partners were tested as result of partner notification, and 26
were newly diagnosed with HIV. The case-finding effectiveness of the program was
18.4%. CONCLUSION: This pilot program provides evidence of the effectiveness of a
partner notification program implemented in healthcare settings. This active
partner notification program was feasible, acceptable to the user, and identified
a high proportion of HIV-infected patients previously unaware of their status.
PMID- 25849450
TI - Catecholaminergic innervation of central and peripheral auditory circuitry varies
with reproductive state in female midshipman fish, Porichthys notatus.
AB - In seasonal breeding vertebrates, hormone regulation of catecholamines, which
include dopamine and noradrenaline, may function, in part, to modulate behavioral
responses to conspecific vocalizations. However, natural seasonal changes in
catecholamine innervation of auditory nuclei is largely unexplored, especially in
the peripheral auditory system, where encoding of social acoustic stimuli is
initiated. The plainfin midshipman fish, Porichthys notatus, has proven to be an
excellent model to explore mechanisms underlying seasonal peripheral auditory
plasticity related to reproductive social behavior. Recently, we demonstrated
robust catecholaminergic (CA) innervation throughout the auditory system in
midshipman. Most notably, dopaminergic neurons in the diencephalon have
widespread projections to auditory circuitry including direct innervation of the
saccule, the main endorgan of hearing, and the cholinergic octavolateralis
efferent nucleus (OE) which also projects to the inner ear. Here, we tested the
hypothesis that gravid, reproductive summer females show differential CA
innervation of the auditory system compared to non-reproductive winter females.
We utilized quantitative immunofluorescence to measure tyrosine hydroxylase
immunoreactive (TH-ir) fiber density throughout central auditory nuclei and the
sensory epithelium of the saccule. Reproductive females exhibited greater density
of TH-ir innervation in two forebrain areas including the auditory thalamus and
greater density of TH-ir on somata and dendrites of the OE. In contrast, non
reproductive females had greater numbers of TH-ir terminals in the saccule and
greater TH-ir fiber density in a region of the auditory hindbrain as well as
greater numbers of TH-ir neurons in the preoptic area. These data provide
evidence that catecholamines may function, in part, to seasonally modulate the
sensitivity of the inner ear and, in turn, the appropriate behavioral response to
reproductive acoustic signals.
PMID- 25849452
TI - Redox-dependent chaperone/peroxidase function of 2-Cys-Prx from the
cyanobacterium Anabaena PCC7120: role in oxidative stress tolerance.
AB - BACKGROUND: Cyanobacteria, progenitors of plant chloroplasts, provide a suitable
model system for plants to study adaptation towards different abiotic stresses.
Genome of the filamentous, heterocystous, nitrogen-fixing cyanobacterium Anabaena
PCC7120 harbours a single gene (alr4641) encoding a typical 2-Cys-Peroxiredoxins
(2-Cys-Prxs). 2-Cys-Prxs are thiol-based peroxidases that also function as
molecular chaperones in plants and other systems. The Alr4641 protein from
Anabaena PCC7120 shows high level biochemical similarities with the plant 2-Cys
Prx. The physiological role played by the Alr4641 protein in Anabaena was
addressed in this study. RESULTS: In Anabaena PCC7120, alr4641 transcript
/Alr4641 protein was induced in response to abiotic stresses and its promoter was
active in the vegetative cells as well as heterocysts. The wild-type Alr4641
protein or Alr4641 lacking the peroxidatic cysteine (Alr4641C56S) or the
resolving cysteine (Alr4641C178S) existed as higher oligomers in their native
form. The wild-type or the mutant Alr4641 proteins showed similar chaperone
activity, but only the wild-type protein exhibited peroxidase activity indicating
that unlike peroxidase activity, chaperone activity was not dependent on
cysteines. In contrast to other 2-Cys-Prxs, chaperone/peroxidase activity of
Alr4641 was dependent on its redox state and not oligomerization status. Alr4641
could protect plasmid DNA from oxidative damage and physically associate with
NADPH-dependent thioredoxin reductase (NTRC). Like 2-Cys-Prxs from plants (e.g.
rice), Alr4641 could detoxify various peroxides using NTRC as reductant. On
exposure to H2O2, recombinant Anabaena PCC7120 strain over-expressing Alr4641
(An4641+) showed reduced content of reactive oxygen species (ROS), intact
photosynthetic functions and consequently better survival than the wild-type
Anabaena PCC7120, indicating that Alr4641 can protect Anabaena from oxidative
stress. CONCLUSIONS: The peroxidase/chaperone function of Alr4641, its inherent
transcriptional/translational induction under different abiotic stresses and
localization in both vegetative cells and heterocysts could be an adaptive
strategy to battle various oxidative stresses that Anabaena encounters during its
growth. Moreover, the recombinant Anabaena strain over expressing Alr4641 showed
higher resistance to oxidative stress, suggesting its potential to serve as
stress-tolerant biofertilizers in rice fields.
PMID- 25849453
TI - Ecdysteroids regulate the levels of Molt-Inhibiting Hormone (MIH) expression in
the blue crab, Callinectes sapidus.
AB - Arthropod molt is coordinated through the interplay between ecdysteroids and
neuropeptide hormones. In crustaceans, changes in the activity of Y-organs during
the molt cycle have been regulated by molt-inhibiting hormone (MIH) and
crustacean hyperglycemic hormone (CHH). Little has been known of the mode of
direct effects of ecdysteroids on the levels of MIH and CHH in the eyestalk
ganglia during the molt cycle. This study focused on a putative feedback of
ecdysteroids on the expression levels of MIH transcripts using in vitro
incubation study with ecdysteroids and in vivo RNAi in the blue crab, Callinectes
sapidus. Our results show a specific expression of ecdysone receptor (EcR) in
which EcR1 is the major isoform in eyestalk ganglia. The initial elevation of MIH
expression at the early premolt stages is replicated by in vitro incubations of
eyestalk ganglia with ecdysteroids that mimic the intrinsic conditions of D0
stage: the concentration (75 ng/ml) and composition (ponasterone A and 20
hydroxyecdysone at a 3:1 (w:w) ratio). Additionally, multiple injections of EcR1
dsRNA reduce MIH expression by 67%, compared to the controls. Our data provide
evidence on a putative feedback mechanism of hormonal regulation during molting
cycle, specifically how the molt cycle is repeated during the life cycle of
crustaceans. The elevated concentrations of ecdysteroids at early premolt stage
may act positively on the levels of MIH expression in the eyestalk ganglia.
Subsequently, the increased MIH titers in the hemolymph at postmolt would inhibit
the synthesis and release of ecdysteroids by Y-organs, resulting in re-setting
the subsequent molt cycle.
PMID- 25849454
TI - Macrocyclic lactones differ in interaction with recombinant P-glycoprotein 9 of
the parasitic nematode Cylicocylus elongatus and ketoconazole in a yeast growth
assay.
AB - Macrocyclic lactones (MLs) are widely used parasiticides against nematodes and
arthropods, but resistance is frequently observed in parasitic nematodes of
horses and livestock. Reports claiming resistance or decreased susceptibility in
human nematodes are increasing. Since no target site directed ML resistance
mechanisms have been identified, non-specific mechanisms were frequently
implicated in ML resistance, including P-glycoproteins (Pgps, designated ABCB1 in
vertebrates). Nematode genomes encode many different Pgps (e.g. 10 in the sheep
parasite Haemonchus contortus). ML transport was shown for mammalian Pgps, Pgps
on nematode egg shells, and very recently for Pgp-2 of H. contortus. Here, Pgp-9
from the equine parasite Cylicocyclus elongatus (Cyathostominae) was expressed in
a Saccharomyces cerevisiae strain lacking seven endogenous efflux transporters.
Pgp was detected on these yeasts by flow cytometry and chemiluminescence using
the monoclonal antibody UIC2, which is specific for the active Pgp conformation.
In a growth assay, Pgp-9 increased resistance to the fungicides ketoconazole,
actinomycin D, valinomycin and daunorubicin, but not to the anthelmintic
fungicide thiabendazole. Since no fungicidal activity has been described for MLs,
their interaction with Pgp-9 was investigated in an assay involving two drugs:
Yeasts were incubated with the highest ketoconazole concentration not affecting
growth plus increasing concentrations of MLs to determine competition between or
modulation of transport of both drugs. Already equimolar concentrations of
ivermectin and eprinomectin inhibited growth, and at fourfold higher ML
concentrations growth was virtually abolished. Selamectin and doramectin did not
increase susceptibility to ketoconazole at all, although doramectin has been
shown previously to strongly interact with human and canine Pgp. An intermediate
interaction was observed for moxidectin. This was substantiated by increased
binding of UIC2 antibodies in the presence of ivermectin, moxidectin,
daunorubicin and ketoconazole but not selamectin. These results demonstrate
direct effects of MLs on a recombinant nematode Pgp in an ML-specific manner.
PMID- 25849455
TI - Xenotransplantation of human adipose-derived stem cells in zebrafish embryos.
AB - Zebrafish is a widely used animal model with well-characterized background in
developmental biology. The fate of human adipose-derived stem cells (ADSCs) after
their xenotransplantation into the developing embryos of zebrafish is unknown.
Therefore, human ADSCs were firstly isolated, and then transduced with lentiviral
vector system carrying a green fluorescent protein (GFP) reporter gene, and
followed by detection of their cell viability and the expression of cell surface
antigens. These GFP-expressing human ADSCs were transplanted into the zebrafish
embryos at 3.3-4.3 hour post-fertilization (hpf). Green fluorescent signal, the
proliferation and differentiation of human ADSCs in recipient embryos were
respectively examined using fluorescent microscopy and immunohistochemical
staining. The results indicated that human ADSCs did not change their cell
viability and the expression levels of cell surface antigens after GFP
transduction. Microscopic examination demonstrated that green fluorescent signals
of GFP expressed in the transplanted cells were observed in the embryos and larva
fish at post-transplantation. The positive staining of Ki-67 revealed the
survival and proliferation of human ADSCs in fish larvae after transplantation.
The expression of CD105 was observable in the xenotransplanted ADSCs, but CD31
expression was undetectable. Therefore, our results indicate that human ADSCs
xenotransplanted in the zebrafish embryos not only can survive and proliferate at
across-species circumstance, but also seem to maintain their undifferentiation
status in a short term. This xenograft model of zebrafish embryos may provide a
promising and useful technical platform for the investigation of biology and
physiology of stem cells in vivo.
PMID- 25849457
TI - Newcastle disease virus (NDV) induces protein oxidation and nitration in brain
and liver of chicken: Ameliorative effect of vitamin E.
AB - The present study was aimed at investigating the therapeutic efficacy of vitamin
E on oxidative injury in brain and liver of Newcastle disease virus (NDV)
challenged chickens. We have analyzed the xanthine oxidase (XOD) activity; uric
acid (UA) levels and superoxide radical generation by using electron spin
resonance spectroscopy. Further, protein oxidation, nitration and apoptosis were
evaluated in the brain and liver of the control, NDV-infected and NDV+Vit. E
treated groups. A significant elevation was observed in XOD activity and UA
levels in brain (p<0.001) and liver (p<0.05) of NDV infected birds when compared
to controls. Further, significant increase in the production of superoxides,
enhanced intracellular protein carbonyls and nitrates were observed in the brain
and liver of NDV-infected birds over healthy subjects. Apoptosis studies also
suggested that a larger number of TUNEL positive cells were observed in brain and
a moderately in liver of NDV-infected chickens. However, all these perturbations
were significantly ameliorated in NDV+Vit. E treated chickens as compared to NDV
infected birds. Taken together, our results suggested that NDV-induced neuronal
and hepatic damage at least in part mediates oxidative stress and on the other
hand, supplementation of vitamin E mitigates NDV-induced oxidative damage thereby
protects brain and liver of chickens. These findings could provide new insights
into the understanding of NDV pathogenesis and therapeutic effects of dietary
antioxidants.
PMID- 25849458
TI - Azadirachtin-induced apoptosis involves lysosomal membrane permeabilization and
cathepsin L release in Spodoptera frugiperda Sf9 cells.
AB - Azadirachtin as a kind of botanical insecticide has been widely used in pest
control. We previously reported that azadirachtin could induce apoptosis of
Spodoptera litura cultured cell line Sl-1, which involves in the up-regulation of
P53 protein. However, the detailed mechanism of azadirachtin-induced apoptosis is
not clearly understood in insect cultured cells. The aim of the present study was
to address the involvement of lysosome and lysosomal protease in azadirachtin
induced apoptosis in Sf9 cells. The result confirmed that azadirachtin indeed
inhibited proliferation and induced apoptosis. The lysosomes were divided into
different types as time-dependent manner, which suggested that changes of
lysosomes were necessarily physiological processes in azadirachtin-induced
apoptosis in Sf9 cells. Interestingly, we noticed that azadirachtin could trigger
lysosomal membrane permeabilization and cathepsin L releasing to cytosol. Z-FF
FMK (a cathepsin L inhibitor), but not CA-074me (a cathepsin B inhibitor), could
effectively hinder the apoptosis induced by azadirachtin in Sf9 cells. Meanwhile,
the activity of caspase-3 could also be inactivated by the inhibition of
cathepsin L enzymatic activity induced by Z-FF-FMK. Taken together, our findings
suggest that azadirachtin could induce apoptosis in Sf9 cells in a lysosomal
pathway, and cathepsin L plays a pro-apoptosis role in this process through
releasing to cytosol and activating caspase-3.
PMID- 25849456
TI - Features of two new proteins with OmpA-like domains identified in the genome
sequences of Leptospira interrogans.
AB - Leptospirosis is an acute febrile disease caused by pathogenic spirochetes of the
genus Leptospira. It is considered an important re-emerging infectious disease
that affects humans worldwide. The knowledge about the mechanisms by which
pathogenic leptospires invade and colonize the host remains limited since very
few virulence factors contributing to the pathogenesis of the disease have been
identified. Here, we report the identification and characterization of two new
leptospiral proteins with OmpA-like domains. The recombinant proteins, which
exhibit extracellular matrix-binding properties, are called Lsa46 - LIC13479 and
Lsa77 - LIC10050 (Leptospiral surface adhesins of 46 and 77 kDa, respectively).
Attachment of Lsa46 and Lsa77 to laminin was specific, dose dependent and
saturable, with KD values of 24.3 +/- 17.0 and 53.0 +/- 17.5 nM, respectively.
Lsa46 and Lsa77 also bind plasma fibronectin, and both adhesins are plasminogen
(PLG)-interacting proteins, capable of generating plasmin (PLA) and as such,
increase the proteolytic ability of leptospires. The proteins corresponding to
Lsa46 and Lsa77 are present in virulent L. interrogans L1-130 and in saprophyte
L. biflexa Patoc 1 strains, as detected by immunofluorescence. The adhesins are
recognized by human leptospirosis serum samples at the onset and convalescent
phases of the disease, suggesting that they are expressed during infection. Taken
together, our data could offer valuable information to the understanding of
leptospiral pathogenesis.
PMID- 25849459
TI - Oxidative stress, mitochondrial perturbations and fetal programming of renal
disease induced by maternal smoking.
AB - An adverse in-utero environment is increasingly recognized to predispose to
chronic disease in adulthood. Maternal smoking remains the most common modifiable
adverse in-utero exposure leading to low birth weight, which is strongly
associated with chronic kidney disease (CKD) in later life. In order to
investigate underlying mechanisms for such susceptibility, female Balb/c mice
were sham or cigarette smoke-exposed (SE) for 6 weeks before mating, throughout
gestation and lactation. Offspring kidneys were examined for oxidative stress,
expression of mitochondrial proteins, mitochondrial structure as well as renal
functional parameters on postnatal day 1, day 20 (weaning) and week 13 (adult
age). From birth throughout adulthood, SE offspring had increased renal levels of
mitochondrial-derived reactive oxygen species (ROS), which left a footprint on
DNA with increased 8-hydroxydeoxyguanosin (8-OHdG) in kidney tubular cells.
Mitochondrial structural abnormalities were seen in SE kidneys at day 1 and week
13 along with a reduction in oxidative phosphorylation (OXPHOS) proteins and
activity of mitochondrial antioxidant Manganese superoxide dismutase (MnSOD).
Smoke exposure also resulted in increased mitochondrial DNA copy number (day 1
week 13) and lysosome density (day 1 and week 13). The appearance of
mitochondrial defects preceded the onset of albuminuria at week 13. Thus,
mitochondrial damage caused by maternal smoking may play an important role in
development of CKD at adult life.
PMID- 25849460
TI - 1H NMR metabolic profiling of plasma reveals additional phenotypes in knockout
mouse models.
AB - The International Mouse Phenotyping Consortium program has been established to
ascribe biological functions to systematically knocked-out (KO) genes by in vivo
and ex vivo phenotyping. The plasma clinical chemistry screen includes an
assessment of liver, kidney, and bone function and provides a basic lipid profile
and histopathology reports on 32 tissues. We report on the inclusion of plasma
analysis by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. (1)H NMR
spectroscopy data are summarized from 116 running baseline controls with 18
homozygous and 2 heterozygous KO mouse lines along with wild-type controls
(typically n = 7 per gender). For the baseline group, the intersample variation
of (1)H NMR glucose measurement was 12%, and the (1)H NMR spectroscopy data were
influenced by gender and feeding status. There were good correlations between the
clinical chemistry and the (1)H NMR spectroscopy measurements for glucose,
triglycerides, and HDL cholesterol. Significant differences were observed in two
KO lines, Agl (MGI: 1924809) and Bbs5 (MGI: 1919819), by (1)H NMR spectroscopy,
clinical chemistry, and histopathology. In a further two KO lines, Elmod1 (MGI:
3583900) and Emc10 (MGI: 1916933), (1)H NMR metabolic differences were observed,
but no other ex vivo changes were detected. In the remaining 16 lines, no ex vivo
abnormal phenotypes were observed. Plasma (1)H NMR spectroscopy can therefore
provide a novel perspective on the function of knocked-out genes.
PMID- 25849461
TI - Periodontitis and Porphyromonas gingivalis in preclinical stage of arthritis
patients.
AB - PURPOSE: To determine whether the presence of periodontitis (PD) and
Porphyromonas gingivalis (Pg) in the subgingival biofilm associates with the
development of rheumatoid arthritis (RA) in treatment naive preclinical stage of
arthritis patients. METHODS: We conducted a prospective cohort study of 72
consecutive patients with arthralgia who had never been treated with any anti
rheumatic drugs or glucocorticoids. Periodontal status at baseline was assessed
by dentists. PD was defined stringently by the maximal probing depth?4 mm, or by
the classification by the 5th European Workshop in Periodontology (EWP) in 2005
using attachment loss. Up to eight plaque samples were obtained from each patient
and the presence of Pg was determined by Taqman PCR. The patients were followed
up for 2 years and introduction rate of methotrexate (MTX) treatment on the
diagnosis of RA was compared in patients with or without PD or Pg. RESULTS:
Patients with PD (probing depth?4mm) had higher arthritis activity (p = 0.02) and
higher risk for future introduction of MTX treatment on the diagnosis of RA
during the follow up than patients without PD (Hazard ratio 2.68, p = 0.03).
Arthritis activity and risk for MTX introduction increased with the severity of
PD assessed by EWP, although not statistically significant. On the other hand,
presence of Pg was not associated with arthritis activity (p = 0.72) or the risk
for MTX introduction (p = 0.45). CONCLUSION: In treatment naive arthralgia
patients, PD, but not the presence of Pg, associates with arthritis activity and
future requirement of MTX treatment on the diagnosis of RA.
PMID- 25849462
TI - Experimental determination of the membrane topology of the Plasmodium protease
Plasmepsin V.
AB - The malaria parasite exports hundreds of proteins into its host cell. The
majority of exported proteins contain a Host-Targeting motif (also known as a
Plasmodium export element) that directs them for export. Prior to export, the
Host-Targeting motif is cleaved by the endoplasmic reticulum-resident protease
Plasmepsin V and the newly generated N-terminus is N-alpha-acetylated by an
unidentified enzyme. The cleaved, N-alpha-acetylated protein is trafficked to the
parasitophorous vacuole, where it is translocated across the vacuole membrane. It
is clear that cleavage and N-alpha-acetylation of the Host-Targeting motif occur
at the endoplasmic reticulum, and it has been proposed that Host-Targeting motif
cleavage and N-alpha-acetylation occur either on the luminal or cytosolic side of
the endoplasmic reticulum membrane. Here, we use self-associating 'split'
fragments of GFP to determine the topology of Plasmepsin V in the endoplasmic
reticulum membrane; we show that the catalytic protease domain of Plasmepsin V
faces the endoplasmic reticulum lumen. These data support a model in which the
Host-Targeting motif is cleaved and N-alpha-acetylated in the endoplasmic
reticulum lumen. Furthermore, these findings suggest that cytosolic N-alpha
acetyltransferases are unlikely to be candidates for the N-alpha
acetyltransferase of Host-Targeting motif-containing exported proteins.
PMID- 25849463
TI - Characterizing newly repopulated microglia in the adult mouse: impacts on animal
behavior, cell morphology, and neuroinflammation.
AB - Microglia are the primary immune cell in the brain and are postulated to play
important roles outside of immunity. Administration of the dual colony
stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor, PLX3397, to adult
mice results in the elimination of ~99% of microglia, which remain eliminated for
as long as treatment continues. Upon removal of the inhibitor, microglia rapidly
repopulate the entire adult brain, stemming from a central nervous system (CNS)
resident progenitor cell. Using this method of microglial elimination and
repopulation, the role of microglia in both healthy and diseased states can be
explored. Here, we examine the responsiveness of newly repopulated microglia to
an inflammatory stimulus, as well as determine the impact of these cells on
behavior, cognition, and neuroinflammation. Two month-old wild-type mice were
placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397
diet was then removed in a subset of animals to allow microglia to repopulate and
behavioral testing conducted beginning at 14 d repopulation. Finally,
inflammatory profiling of the microglia-repopulated brain in response to
lipopolysaccharide (LPS; 0.25 mg/kg) or phosphate buffered saline (PBS) was
determined 21 d after inhibitor removal using quantitative real time polymerase
chain reaction (RT-PCR), as well as detailed analyses of microglial morphologies.
We find mice with repopulated microglia to perform similarly to controls by
measures of behavior, cognition, and motor function. Compared to control/resident
microglia, repopulated microglia had larger cell bodies and less complex
branching in their processes, which resolved over time after inhibitor removal.
Inflammatory profiling revealed that the mRNA gene expression of repopulated
microglia was similar to normal resident microglia and that these new cells
appear functional and responsive to LPS. Overall, these data demonstrate that
newly repopulated microglia function similarly to the original resident microglia
without any apparent adverse effects in healthy adult mice.
PMID- 25849464
TI - Structural and functional roles of glycosylation in fungal laccase from Lentinus
sp.
AB - Laccases are multi-copper oxidases that catalyze the oxidation of various organic
and inorganic compounds by reducing O2 to water. Here we report the crystal
structure at 1.8 A resolution of a native laccase (designated nLcc4) isolated
from a white-rot fungus Lentinus sp. nLcc4 is composed of three cupredoxin-like
domains D1-D3 each folded into a Greek key beta-barrel topology. T1 and T2/T3
copper binding sites and three N-glycosylated sites at Asn75, Asn238, and Asn458
were elucidated. Initial rate kinetic analysis revealed that the kcat, Km, and
kcat/Km of nLcc4 with substrate ABTS were 3,382 s-1, 65.0 +/- 6.5 MUM, and 52 s
1MUM-1, respectively; and the values with lignosulfonic acid determined using
isothermal titration calorimetry were 0.234 s-1, 56.7 +/- 3.2 MUM, and 0.004 s
1MUM-1, respectively. Endo H-deglycosylated nLcc4 (dLcc4), with only one GlcNAc
residue remaining at each of the three N-glycosylation sites in the enzyme,
exhibited similar kinetic efficiency and thermal stability to that of nLcc4. The
isolated Lcc4 gene contains an open reading frame of 1563 bp with a deduced
polypeptide of 521 amino acid residues including a predicted signaling peptide of
21 residues at the N-terminus. Recombinant wild-type Lcc4 and mutant enzymes
N75D, N238D and N458D were expressed in Pichia pastoris cells to evaluate the
effect on enzyme activity by single glycosylation site deficiency. The mutant
enzymes secreted in the cultural media of P. pastoris cells were observed to
maintain only 4-50% of the activity of the wild-type laccase. Molecular dynamics
simulations analyses of various states of (de-)glycosylation in nLcc support the
kinetic results and suggest that the local H-bond networks between the domain
connecting loop D2-D3 and the glycan moieties play a crucial role in the laccase
activity. This study provides new insights into the role of glycosylation in the
structure and function of a Basidiomycete fungal laccase.
PMID- 25849466
TI - A heartfelt thank you to Dr Joel Weaver.
PMID- 25849465
TI - Aspirin use and lung cancer risk: a possible relationship? Evidence from an
updated meta-analysis.
AB - BACKGROUND AND PURPOSE: Growing evidence has emerged and controversial results
reported on possible relationship between aspirin use and lung cancer risk. We,
therefore, conducted this updated and comprehensive meta-analysis to evaluate
this issue, with focus on dose-risk and duration-risk relationships. METHODS: We
searched electronic databases including PUBMED, EMBASE and Cochrane library to
identify eligible studies. Relative risk (RR) and its 95% confidence interval
(CI) were used for cohort studies, while odds ratio (OR) were employed for case
control studies. The random effects and fixed effects models were used for
analyses. RESULTS: 18 studies were identified including 19835 lung cancer cases,
which were eligible for inclusion in the present meta-analysis. Pooled data from
case-control studies showed a significant inverse association between regular
aspirin use and lung cancer risk. But for cohort studies, insignificant
association was detected with little evidence of heterogeneity (RR: 1.05, 95%CI:
0.95 - 1.16; I2: 10.3%, p value: 0.351). In case-control studies, standard
aspirin use (>325mg) was related to lower lung cancer incidence, compared with
low-dose aspirin use (75-100mg). A similar trend was observed in cohort studies.
Besides, when analysis was restricted to long time regular aspirin use (>5
years), insignificant results were reported in both cohort and case-control
studies. Finally, regular aspirin use might result in higher reduction of non
small cell lung cancer incidence among men. CONCLUSIONS: Our findings do not
support the protective effect of regular aspirin use on lung cancer risk. Long
time aspirin use, sex, dose and type of lung cancer might alter the effect of
aspirin use on lung cancer risk. More well-designed studies are needed to further
clarify these associations.
PMID- 25849467
TI - Effect of needle design on pain from dental local anesthetic injections.
AB - The purpose of this randomized, double-blind clinical study was to evaluate the
effectiveness of a larger-bore compared with a standard-bore dental local
anesthetic needle of the same gauge in reducing pain during inferior alveolar
(IA) and long buccal (LB) nerve block injections. Twenty active duty military or
Department of Defense beneficiaries undergoing dental treatment were anesthetized
using a split-mouth design with 4 anesthetic dental injections. Both sides of the
mouth received IA nerve block and LB nerve injections, one using the 27-gauge
large-bore Septoject XL needle and other using a 27-gauge standard-bore Septoject
needle. Patients rated the pain experienced with each method using a visual
analogue scale (VAS). The IA injection mean VAS score and standard deviation were
38.9 +/- 22.7 mm and 37.1 +/- 22.4 mm, respectively, for the larger and standard
bore needles. The LB injection mean VAS score and standard deviation were 33.5 +/
22.8 mm and 35.1 +/- 19.6 mm, respectively, for the larger and standard-bore
needles. The data were analyzed with a paired t test (alpha = .05). No
significant difference was found between the IA (P = .70) or LB injections (P =
.73). The use of a larger-bore 27-gauge needle did not reduce pain on injection
compared with the standard-bore 27-gauge needle.
PMID- 25849468
TI - Independent predictors of delay in emergence from general anesthesia.
AB - Some patients with intellectual disabilities spend longer than others in
emergence from ambulatory general anesthesia for dental treatment. Although
antiepileptic drugs and anesthetics might be involved, an independent predictor
for delay of the emergence remains unclear. Thus, a purpose of this study is to
identify independent factors affecting the delay of emergence from general
anesthesia. This was a retrospective cohort study in dental patients with
intellectual disabilities. Patients in need of sedative premedication were
removed from participants. The outcome was time until emergence from general
anesthesia. Stepwise multivariate regression analysis was used to extract
independent factors affecting the outcome. Antiepileptic drugs and anesthetic
parameters were included as predictor variables. The study included 102 cases.
Clobazam, clonazepam, and phenobarbital were shown to be independent determinants
of emergence time. Parameters relating to anesthetics, patients' backgrounds, and
dental treatment were not independent factors. Delay in emergence time in
ambulatory general anesthesia is likely to be related to the antiepileptic drugs
of benzodiazepine or barbiturates in patients with intellectual disability.
PMID- 25849469
TI - Anesthetic efficacy of meperidine in teeth with symptomatic irreversible
pulpitis.
AB - Achieving adequate pulpal anesthesia in mandibular teeth is always a challenge.
Supplementary injections and using drugs in combination are some methods
implemented to overcome this hurdle. In this randomized clinical trial, use of
meperidine in conjunction with lidocaine in intraligamentary injection did not
exhibit significant improvement in anesthesia.
PMID- 25849470
TI - Anesthetic management by laryngeal mask airway in a patient with a history of
difficult intubation resulting in dental injuries.
AB - Disabled patients may face respiratory problems during general anesthesia because
of head and neck anomalies. We describe a case of dental treatment under general
anesthesia using a laryngeal mask airway in a disabled patient who faced
difficulty in endotracheal intubation on several occasions, 5 of which resulted
in dental injuries.
PMID- 25849471
TI - Suspected intraoperative anaphylaxis to gelatin absorbable hemostatic sponge.
AB - Anaphylaxis under anesthesia is a life-threatening medical emergency that
requires rapid identification and treatment. Allergies to agents with which the
general population are likely to come into contact are usually identified, but
patients are exposed to uncommon agents during anesthesia and surgery. Here, we
describe a case of anaphylaxis under anesthesia implicating Gelfoam sponges.
PMID- 25849472
TI - Dexmedetomidine, ketamine, and midazolam for oral rehabilitation: a case report.
AB - Intravenous sedation is frequently provided by anesthesiologists for phobic
patients undergoing elective dental treatment in outpatient settings. Propofol is
one of the most commonly used anesthetic agents that can result in apnea and
respiratory depression, thereby posing potential difficulties with perioperative
airway management. Dexmedetomidine has been utilized successfully in intravenous
sedation for a wide variety of procedures and holds potential as an alternative
to propofol in outpatient dental settings. However, as a single agent, it may not
provide adequate depth of sedation and analgesia for oral rehabilitation. In this
case report we demonstrate an effective alternative intravenous deep-sedation
technique for an adult phobic patient undergoing oral rehabilitation utilizing 3
agents in combination: dexmedetomidine, ketamine, and midazolam. This combination
of agents may be especially useful for those patients with a history of substance
abuse, where administration of opioids may be undesirable or contraindicated.
PMID- 25849473
TI - Alpha-2 adrenergic receptor agonists: a review of current clinical applications.
AB - The alpha-2 adrenergic receptor agonists have been used for decades to treat
common medical conditions such as hypertension; attention-deficit/hyperactivity
disorder; various pain and panic disorders; symptoms of opioid, benzodiazepine,
and alcohol withdrawal; and cigarette craving. (1) However, in more recent years,
these drugs have been used as adjuncts for sedation and to reduce anesthetic
requirements. This review will provide an historical perspective of this drug
class, an understanding of pharmacological mechanisms, and an insight into
current applications in clinical anesthesiology.
PMID- 25849475
TI - Reply: To PMID 25517557.
PMID- 25849477
TI - Optimal cut-off points on the health anxiety inventory, illness attitude scales
and whiteley index to identify severe health anxiety.
AB - BACKGROUND: Health anxiety can be viewed as a dimensional phenomenon where severe
health anxiety in form of DSM-IV hypochondriasis represents a cut-off where the
health anxiety becomes clinically significant. Three of the most reliable and
used self-report measures of health anxiety are the Health Anxiety Inventory
(HAI), the Illness Attitude Scales (IAS) and the Whiteley Index (WI). Identifying
the optimal cut-offs for classification of presence of a diagnosis of severe
health anxiety on these measures has several advantages in clinical and research
settings. The aim of this study was therefore to investigate the HAI, IAS and WI
as proximal diagnostic instruments for severe health anxiety defined as DSM-IV
hypochondriasis. METHODS: We investigated sensitivity, specificity and predictive
value on the HAI, IAS and WI using a total of 347 adult participants of whom 158
had a diagnosis of severe health anxiety, 97 had obsessive-compulsive disorder
and 92 were healthy non-clinical controls. Diagnostic assessments were conducted
using the Anxiety Disorder Interview Schedule. RESULTS: Optimal cut-offs for
identifying a diagnosis of severe health anxiety was 67 on the HAI, 47 on the
IAS, and 5 on the WI. Sensitivity and specificity were high, ranging from 92.6 to
99.4%. Positive and negative predictive values ranged from 91.6 to 99.4% using
unadjusted prevalence rates. CONCLUSIONS: The HAI, IAS and WI have very good
properties as diagnostic indicators of severe health anxiety and can be used as
cost-efficient proximal estimates of the diagnosis.
PMID- 25849478
TI - SMY2 and SYH1 suppress defects in ribosome biogenesis caused by ebp2 mutations.
AB - Ebp2 is an assembly factor of the 60S ribosomal subunit in yeast. We demonstrate
that overexpression of SMY2 or SYH1 partially suppresses defects in growth and
ribosome biogenesis of ebp2 mutants, and that smy2Delta and syh1Delta exhibit
synthetic growth defects with the ebp2 allele. These results suggest that Smy2
and Syh1 may be involved in ribosome biogenesis in relation to Ebp2.
PMID- 25849479
TI - Global analysis of the Gossypium hirsutum L. Transcriptome during leaf senescence
by RNA-Seq.
AB - BACKGROUND: Leaf senescence is an important developmental programmed degeneration
process that dramatically affects crop quality and yield. The regulation of
senescence is highly complex. Although senescence regulatory genes have been well
characterized in model species such as Arabidopsis and rice, there is little
information on the control of this process in cotton. Here, the senescence
process in cotton (Gossypium hirsutum L.) leaves was investigated over a time
course including young leaf, mature leaf and leaf samples from different
senescence stages using RNA-Seq. RESULTS: Of 24,846 genes detected by mapping the
tags to Gossypium genomes, 3,624 genes were identified as differentially
expressed during leaf senescence. There was some overlap between the genes
identified here and senescence-associated genes previously identified in other
species. Most of the genes related to photosynthesis, chlorophyll metabolism and
carbon fixation were downregulated; whereas those for plant hormone signal
transduction were upregulated. Quantitative real-time PCR was used to evaluate
the results of RNA-Seq for gene expression profiles. Furthermore, 519
differentially expressed transcription factors were identified, notably WRKY,
bHLH and C3H. In addition, 960 genes involved in the metabolism and regulation of
eight hormones were identified, of which many genes involved in the abscisic
acid, brassinosteroid, jasmonic acid, salicylic acid and ethylene pathways were
upregulated, indicating that these hormone-related genes might play crucial roles
in cotton leaf development and senescence. However, most auxin, cytokinin and
gibberellin pathway-related genes were downregulated, suggesting that these three
hormones may act as negative regulators of senescence. CONCLUSIONS: This is the
first high-resolution, multiple time-course, genome-wide comprehensive analysis
of gene expression in cotton. These data are the most comprehensive dataset
currently available for cotton leaf senescence, and will serve as a useful
resource for unraveling the functions of many specific genes involved in cotton
leaf development and senescence.
PMID- 25849480
TI - Asthma, type 1 and type 2 diabetes mellitus, and inflammatory bowel disease
amongst South Asian immigrants to Canada and their children: a population-based
cohort study.
AB - BACKGROUND: There is a high and rising rate of immune-mediated diseases in the
Western world. Immigrants from South Asia have been reported to be at higher risk
upon arrival to the West. We determined the risk of immune-mediated diseases in
South Asian and other immigrants to Ontario, Canada, and their Ontario-born
children. METHODS: Population-based cohorts of patients with asthma, type 1
diabetes (T1DM), type 2 diabetes (T2DM), and inflammatory bowel disease (IBD)
were derived from health administrative data. We determined the standardized
incidence, and the adjusted risk of these diseases in immigrants from South Asia,
immigrants from other regions, compared with non-immigrant residents of Ontario.
The risk of these diseases in the Ontario-born children of immigrants were
compared to the children of non-immigrants. RESULTS: Compared to non-immigrants,
adults from South Asia had higher risk of asthma (IRR 1.56, 95%CI 1.51-1.61) and
T2DM (IRR 2.59, 95%CI 2.53-2.65). Adults from South Asia had lower incidence of
IBD than non-immigrants (IRR 0.32, 95%CI 0.22-0.49), as did immigrants from other
regions (IRR 0.29, 95%CI 0.20-0.42). Compared to non-immigrant children, the
incidence of asthma (IRR 0.66, 95%CI 0.62-0.71) and IBD (IRR 0.47, 95%CI 0.33
0.67) was low amongst immigrant children from South Asia. However, the risk in
Ontario-born children of South Asian immigrants relative to the children of non
immigrants was higher for asthma (IRR 1.75, 95%CI 1.69-1.81) and less attenuated
for IBD (IRR 0.90, 95%CI 0.65-1.22). CONCLUSION: Early-life environmental
exposures may trigger a genetic predisposition to the development of asthma and
IBD in South Asian immigrants and their Canada-born children.
PMID- 25849481
TI - Gait mechanics in patients with chronic obstructive pulmonary disease.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by the
frequent association of disease outside the lung. The objective of this study was
to determine the presence of biomechanical gait abnormalities in COPD patients
compared to healthy controls while well rested and without rest. METHODS:
Patients with COPD (N = 17) and aged-matched, healthy controls (N = 21) walked at
their self-selected pace down a 10-meter walkway while biomechanical gait
variables were collected. A one-minute rest was given between each of the five
collected trials to prevent tiredness (REST condition). Patients with COPD then
walked at a self-selected pace on a treadmill until the onset of self-reported
breathlessness or leg tiredness. Subjects immediately underwent gait analysis
with no rest between each of the five collected trials (NO REST condition).
Statistical models with and without covariates age, gender, and smoking history
were used. RESULTS: After adjusting for covariates, COPD patients demonstrated
more ankle power absorption in mid-stance (P = 0.006) than controls during both
conditions. Both groups during NO REST demonstrated increased gait speed (P =
0.04), stride length (P = 0.03), and peak hip flexion (P = 0.04) with decreased
plantarflexion moment (P = 0.04) and increased knee power absorption (P = 0.04)
as compared to REST. A significant interaction revealed that peak ankle
dorsiflexion moment was maintained from REST to NO REST for COPD but increased
for controls (P < 0.01). Stratifying by disease severity did not alter these
findings, except that step width decreased in NO REST as compared to REST (P =
0.01). Standardized effect sizes of significant effects varied from 0.5 to 0.98.
CONCLUSIONS: Patients with COPD appear to demonstrate biomechanical gait changes
at the ankle as compared to healthy controls. This was seen not only in increased
peak ankle power absorption during no rest but was also demonstrated by a lack of
increase in peak ankle dorsiflexion moment from the REST to the NO REST condition
as compared to the healthy controls. Furthermore, a wider step width has been
associated with fall risk and this could account for the increased incidence of
falls in patients with COPD.
PMID- 25849483
TI - A stock market forecasting model combining two-directional two-dimensional
principal component analysis and radial basis function neural network.
AB - In this paper, we propose and implement a hybrid model combining two-directional
two-dimensional principal component analysis ((2D)2PCA) and a Radial Basis
Function Neural Network (RBFNN) to forecast stock market behavior. First, 36
stock market technical variables are selected as the input features, and a
sliding window is used to obtain the input data of the model. Next, (2D)2PCA is
utilized to reduce the dimension of the data and extract its intrinsic features.
Finally, an RBFNN accepts the data processed by (2D)2PCA to forecast the next
day's stock price or movement. The proposed model is used on the Shanghai stock
market index, and the experiments show that the model achieves a good level of
fitness. The proposed model is then compared with one that uses the traditional
dimension reduction method principal component analysis (PCA) and independent
component analysis (ICA). The empirical results show that the proposed model
outperforms the PCA-based model, as well as alternative models based on ICA and
on the multilayer perceptron.
PMID- 25849482
TI - Relaxin-3 receptor (RXFP3) signalling mediates stress-related alcohol preference
in mice.
AB - Stressful life events are causally linked with alcohol use disorders (AUDs),
providing support for a hypothesis that alcohol consumption is aimed at stress
reduction. We have previously shown that expression of relaxin-3 mRNA in rat
brain correlates with alcohol intake and that central antagonism of relaxin-3
receptors (RXFP3) prevents stress-induced reinstatement of alcohol-seeking.
Therefore the objectives of these studies were to investigate the impact of Rxfp3
gene deletion in C57BL/6J mice on baseline and stress-related alcohol
consumption. Male wild-type (WT) and Rxfp3 knockout (KO) (C57/B6JRXFP3TM1/DGen)
littermate mice were tested for baseline saccharin and alcohol consumption and
preference over water in a continuous access two-bottle free-choice paradigm.
Another cohort of mice was subjected to repeated restraint followed by swim
stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde
dehydrogenase activity was assessed in mice following chronic alcohol intake and
in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and
alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice
displayed a stress-induced reduction in alcohol preference that was not observed
in WT littermates. Notably, this phenotype, once established, persisted for at
least six weeks after cessation of stress exposure. These findings suggest that
in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol
preference during and after stress, but does not appear to strongly regulate the
primary reinforcing effects of alcohol.
PMID- 25849484
TI - Potential role of Notch signalling in CD34+ chronic myeloid leukaemia cells:
cross-talk between Notch and BCR-ABL.
AB - Notch signalling is critical for haemopoietic stem cell (HSC) self-renewal and
survival. The role of Notch signalling has been reported recently in chronic
myeloid leukaemia (CML) - a stem cell disease characterized by BCR-ABL tyrosine
kinase activation. Therefore, we studied the relationship between BCR-ABL and
Notch signalling and assessed the expression patterns of Notch and its downstream
target Hes1 in CD34+ stem and progenitor cells from chronic-phase CML patients
and bone marrow (BM) from normal subjects (NBM). We found significant
upregulation (p<0.05) of Notch1, Notch2 and Hes1 on the most primitive CD34+Thy+
subset of CML CD34+ cells suggesting that active Notch signalling in CML
primitive progenitors. In addition, Notch1 was also expressed in distinct
lymphoid and myeloid progenitors within the CD34+ population of primary CML
cells. To further delineate the possible role and interactions of Notch with BCR
ABL in CD34+ primary cells from chronic-phase CML, we used P-crkl detection as a
surrogate assay of BCR-ABL tyrosine kinase activity. Our data revealed that
Imatinib (IM) induced BCR-ABL inhibition results in significant (p<0.05)
upregulation of Notch activity, assessed by Hes1 expression. Similarly,
inhibition of Notch leads to hyperactivation of BCR-ABL. This antagonistic
relationship between Notch and BCR-ABL signalling was confirmed in K562 and ALL
SIL cell lines. In K562, we further validated this antagonistic relationship by
inhibiting histone deacetylase (HDAC) - an effector pathway of Hes1, using
valproic acid (VPA) - a HDAC inhibitor. Finally, we also confirmed the potential
antagonism between Notch and BCR/ABL in In Vivo, using publically available GSE
database, by analysing gene expression profile of paired samples from chronic
phase CML patients pre- and post-Imatinib therapy. Thus, we have demonstrated an
antagonistic relationship between Notch and BCR-ABL in CML. A combined inhibition
of Notch and BCR-ABL may therefore provide superior clinical response over
tyrosine-kinase inhibitor monotherapy by targeting both quiescent leukaemic stem
cells and differentiated leukaemic cells and hence must be explored.
PMID- 25849485
TI - Acrolein impairs the cholesterol transport functions of high density
lipoproteins.
AB - High density lipoproteins (HDL) are considered athero-protective, primarily due
to their role in reverse cholesterol transport, where they transport cholesterol
from peripheral tissues to the liver for excretion. The current study was
designed to determine the impact of HDL modification by acrolein, a highly
reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol
transport functions of HDL. HDL was chemically-modified with acrolein and
immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking,
as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of
acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC)
from COS-7 cells transiently expressing SR-BI was significantly decreased.
Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid
accumulation in murine macrophages as judged by Oil Red O staining. The ability
of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE)
into SR-BI-expressing cells was reduced compared to native HDL. Together, the
findings from our studies suggest that acrolein modification of HDL produces a
dysfunctional particle that may ultimately promote atherogenesis by impairing
functions that are critical in the reverse cholesterol transport pathway.
PMID- 25849486
TI - Interplay between constraints, objectives, and optimality for genome-scale
stoichiometric models.
AB - High-throughput data generation and genome-scale stoichiometric models have
greatly facilitated the comprehensive study of metabolic networks. The
computation of all feasible metabolic routes with these models, given
stoichiometric, thermodynamic, and steady-state constraints, provides important
insights into the metabolic capacities of a cell. How the feasible metabolic
routes emerge from the interplay between flux constraints, optimality objectives,
and the entire metabolic network of a cell is, however, only partially
understood. We show how optimal metabolic routes, resulting from flux balance
analysis computations, arise out of elementary flux modes, constraints, and
optimization objectives. We illustrate our findings with a genome-scale
stoichiometric model of Escherichia coli metabolism. In the case of one flux
constraint, all feasible optimal flux routes can be derived from elementary flux
modes alone. We found up to 120 million of such optimal elementary flux modes. We
introduce a new computational method to compute the corner points of the optimal
solution space fast and efficiently. Optimal flux routes no longer depend
exclusively on elementary flux modes when we impose additional constraints; new
optimal metabolic routes arise out of combinations of elementary flux modes. The
solution space of feasible metabolic routes shrinks enormously when additional
objectives---e.g. those related to pathway expression costs or pathway length--
are introduced. In many cases, only a single metabolic route remains that is both
feasible and optimal. This paper contributes to reaching a complete topological
understanding of the metabolic capacity of organisms in terms of metabolic flux
routes, one that is most natural to biochemists and biotechnologists studying and
engineering metabolism.
PMID- 25849487
TI - Dual targeted therapy with p53 siRNA and Epigallocatechingallate in a triple
negative breast cancer cell model.
AB - Triple-negative breast cancer (TNBC) is a highly aggressive phenotype that is
resistant to standard therapy. Thus, the development of alternative therapeutic
strategies for TNBC is essential. The purpose of our in vitro study was to
evaluate the impact of p53 gene silencing in conjunction with the administration
of a natural compound, epigallocatechingallate (EGCG). RT2Profiler PCR Array
technology was used to evaluate the impact of dual treatment on the main genes
involved in apoptosis in the Hs578T cell culture model of TNBC. Gene expression
analysis revealed 28 genes were significantly altered (16 upregulated and 12
downregulated) in response to combined p53 siRNA and EGCG treatment. Further
analysis revealed that p53 siRNA and EGCG dual therapy leads to the activation of
pro-apoptotic genes and the inhibition of pro-survival genes, autophagy, and cell
network formation. These results indicate that this dual therapy targets both the
apoptotic and angiogenic pathways, which may improve treatment effectiveness for
tumors resistant to conventional treatment.
PMID- 25849488
TI - Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity
and diversifying selection among chronic and congenital Chagas disease patients.
AB - BACKGROUND: Chagas disease results from infection with the diploid protozoan
parasite Trypanosoma cruzi. T. cruzi is highly genetically diverse, and
multiclonal infections in individual hosts are common, but little studied. In
this study, we explore T. cruzi infection multiclonality in the context of age,
sex and clinical profile among a cohort of chronic patients, as well as paired
congenital cases from Cochabamba, Bolivia and Goias, Brazil using amplicon deep
sequencing technology. METHODOLOGY/ PRINCIPAL FINDINGS: A 450bp fragment of the
trypomastigote TcGP63I surface protease gene was amplified and sequenced across
70 chronic and 22 congenital cases on the Illumina MiSeq platform. In addition, a
second, mitochondrial target--ND5--was sequenced across the same cohort of cases.
Several million reads were generated, and sequencing read depths were normalized
within patient cohorts (Goias chronic, n = 43, Goias congenital n = 2, Bolivia
chronic, n = 27; Bolivia congenital, n = 20), Among chronic cases, analyses of
variance indicated no clear correlation between intra-host sequence diversity and
age, sex or symptoms, while principal coordinate analyses showed no clustering by
symptoms between patients. Between congenital pairs, we found evidence for the
transmission of multiple sequence types from mother to infant, as well as
widespread instances of novel genotypes in infants. Finally, non-synonymous to
synonymous (dn:ds) nucleotide substitution ratios among sequences of TcGP63Ia and
TcGP63Ib subfamilies within each cohort provided powerful evidence of strong
diversifying selection at this locus. CONCLUSIONS/SIGNIFICANCE: Our results shed
light on the diversity of parasite DTUs within each patient, as well as the
extent to which parasite strains pass between mother and foetus in congenital
cases. Although we were unable to find any evidence that parasite diversity
accumulates with age in our study cohorts, putative diversifying selection within
members of the TcGP63I gene family suggests a link between genetic diversity
within this gene family and survival in the mammalian host.
PMID- 25849490
TI - A novel system for evaluating drought-cold tolerance of grapevines using
chlorophyll fluorescence.
AB - BACKGROUND: Grape production in continental climatic regions suffers from the
combination of drought and cold stresses during winter. Developing a reliable
system to simulate combined drought-cold stress and to determine physiological
responses and regulatory mechanisms is important. Evaluating tolerance to
combined stress at germplasm level is crucial to select parents for breeding
grapevines. RESULTS: In the present study, two species, namely, Vitis amurensis
and V. vinifera cv. 'Muscat Hamburg', were used to develop a reliable system for
evaluating their tolerance to drought-cold stress. This system used tissue
cultured grapevine plants, 6% PEG solution, and gradient cooling mode to simulate
drought-cold stress. V. amurensis had a significantly lower LT50 value (the
temperature of 50% electrolyte leakage) than 'Muscat Hamburg' during simulated
drought-cold stress. Thus, the former had higher tolerance than the latter to
drought-cold stress based on electrolyte leakage (EL) measurements. Moreover, the
chlorophyll fluorescence responses of V. amurensis and 'Muscat Hamburg' were also
analyzed under drought-cold stress. The maximum photochemical quantum yield of PS
II (Fv/Fm) exhibited a significant linear correlationship with EL. The
relationship of EL with Fv/Fm in the other four genotypes of grapevines under
drought-cold stress was also detected. CONCLUSIONS: A novel LT50 estimation model
was established, and the LT50 values can be well calculated based on Fv/Fm in
replacement of EL measurement. The Fv/Fm-based model exhibits good reliability
for evaluating the tolerance of different grapevine genotypes to drought-cold
stress.
PMID- 25849491
TI - Design and synthesis of fluorinated dendrimers for sensitive (19)F MRI.
AB - To achieve high sensitivity for (19)F MRI, a class of novel dendritic molecules
with multiple pseudosymmetrical fluorines was designed and efficiently
synthesized. Through iterative bromination and Williamson ether synthesis under
mild conditions, a fluorinated dendrimer with 540 pseudosymmetrical fluorines was
conveniently prepared without performing the group protection in a convergent
way. The dendrimer is characterized by a strong (19)F NMR peak and short
relaxation times. Eventually, an appreciably enhanced (19)F MRI at an extremely
low concentration (18.5 MUM) was achieved, which demonstrated the potential
utility of such dendritic molecules in highly sensitive (19)F MRI.
PMID- 25849489
TI - Accounting for dependence induced by weighted KNN imputation in paired samples,
motivated by a colorectal cancer study.
AB - Missing data can arise in bioinformatics applications for a variety of reasons,
and imputation methods are frequently applied to such data. We are motivated by a
colorectal cancer study where miRNA expression was measured in paired tumor
normal samples of hundreds of patients, but data for many normal samples were
missing due to lack of tissue availability. We compare the precision and power
performance of several imputation methods, and draw attention to the statistical
dependence induced by K-Nearest Neighbors (KNN) imputation. This imputation
induced dependence has not previously been addressed in the literature. We
demonstrate how to account for this dependence, and show through simulation how
the choice to ignore or account for this dependence affects both power and type I
error rate control.
PMID- 25849492
TI - Multishell Au/Ag/SiO2 nanorods with tunable optical properties as single particle
orientation and rotational tracking probes.
AB - Three-layer core-shell plasmonic nanorods (Au/Ag/SiO2-NRs), consisting of a gold
nanorod core, a thin silver shell, and a thin silica layer, were synthesized and
used as optical imaging probes under a differential interference contrast
microscope for single particle orientation and rotational tracking. The localized
surface plasmon resonance modes were enhanced upon the addition of the silver
shell, and the anisotropic optical properties of gold nanorods were maintained.
The silica coating enables surface functionalization with silane coupling agents
and provides enhanced stability and biocompatibility. Taking advantage of the
longitudinal LSPR enhancement, the orientation and rotational information of the
hybrid nanorods on synthetic lipid bilayers and on live cell membranes were
obtained with millisecond temporal resolution using a scientific complementary
metal-oxide-semiconductor camera. The results demonstrate that the as-synthesized
hybrid nanorods are promising imaging probes with improved sensitivity and good
biocompatibility for single plasmonic particle tracking experiments in biological
systems.
PMID- 25849493
TI - Large-volume protein crystal growth for neutron macromolecular crystallography.
AB - Neutron macromolecular crystallography (NMC) is the prevailing method for the
accurate determination of the positions of H atoms in macromolecules. As neutron
sources are becoming more available to general users, finding means to optimize
the growth of protein crystals to sizes suitable for NMC is extremely important.
Historically, much has been learned about growing crystals for X-ray diffraction.
However, owing to new-generation synchrotron X-ray facilities and sensitive
detectors, protein crystal sizes as small as in the nano-range have become
adequate for structure determination, lessening the necessity to grow large
crystals. Here, some of the approaches, techniques and considerations for the
growth of crystals to significant dimensions that are now relevant to NMC are
revisited. These include experimental strategies utilizing solubility diagrams,
ripening effects, classical crystallization techniques, microgravity and
theoretical considerations.
PMID- 25849494
TI - The X-ray structure of human P-cadherin EC1-EC2 in a closed conformation provides
insight into the type I cadherin dimerization pathway.
AB - Cadherins are a large family of calcium-dependent proteins that mediate cellular
adherens junction formation and tissue morphogenesis. To date, the most studied
cadherins are those classified as classical, which are further divided into type
I or type II depending on selected sequence features. Unlike other members of the
classical cadherin family, a detailed structural characterization of P-cadherin
has not yet been fully obtained. Here, the high-resolution crystal structure
determination of the closed form of human P-cadherin EC1-EC2 is reported. The
structure shows a novel, monomeric packing arrangement that provides a further
snapshot in the yet-to-be-achieved complete description of the highly dynamic
cadherin dimerization pathway. Moreover, this is the first multidomain cadherin
fragment to be crystallized and structurally characterized in its closed
conformation that does not carry any extra N-terminal residues before the
naturally occurring aspartic acid at position 1. Finally, two clear alternate
conformations are observed for the critical Trp2 residue, suggestive of a
transient, metastable state. The P-cadherin structure and packing arrangement
shown here provide new and valuable information towards the complete structural
characterization of the still largely elusive cadherin dimerization pathway.
PMID- 25849495
TI - Structural basis of the substrate specificity of the FPOD/FAOD family revealed by
fructosyl peptide oxidase from Eupenicillium terrenum.
AB - The FAOD/FPOD family of proteins has the potential to be useful for the longterm
detection of blood glucose levels in diabetes patients. A bottleneck for this
application is to find or engineer a FAOD/FPOD family enzyme that is specifically
active towards alpha-fructosyl peptides but is inactive towards other types of
glycated peptides. Here, the crystal structure of fructosyl peptide oxidase from
Eupenicillium terrenum (EtFPOX) is reported at 1.9 A resolution. In contrast to
the previously reported structure of amadoriase II, EtFPOX has an open substrate
entrance to accommodate the large peptide substrate. The functions of residues
critical for substrate selection are discussed based on structure comparison and
sequence alignment. This study reveals the first structural details of group I
FPODs that prefer alpha-fructosyl substrates and could provide significant useful
information for uncovering the mechanism of substrate specificity of FAOD/FPODs
and guidance towards future enzyme engineering for diagnostic purposes.
PMID- 25849496
TI - Crystallization and preliminary X-ray crystallographic analysis of the sclerostin
neutralizing Fab AbD09097.
AB - The secreted cystine-knot protein sclerostin was first identified from genetic
screening of patients suffering from the rare bone-overgrowth diseases
sclerosteosis and van Buchem disease. Sclerostin acts a negative regulator of
bone growth through inhibiting the canonical Wnt signalling cascade by binding to
and blocking the Wnt co-receptor LRP5/6. Its function in blocking
osteoblastogenesis makes it an important target for osteoanabolic therapy
approaches to treat osteoporosis, which is characterized by a progressive
decrease in bone mass and density. In this work, the production, crystallization
and preliminary X-ray diffraction data analysis of a sclerostin-neutralizing
human Fab antibody fragment, AbD09097, obtained from a naive antibody library are
reported. Crystals of the Fab AbD09097 belonged to space group P21, with unit
cell parameters a = 45.19, b = 78.49, c = 59.20 A, beta = 95.71 degrees and
diffracted X-rays to a resolution of 1.8 A.
PMID- 25849497
TI - Crystallization and preliminary X-ray diffraction analysis of the interaction of
Aeromonas hydrophila MtaN-1 with S-adenosylhomocysteine.
AB - Prokaryotic 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MtaN) is
a multifunctional enzyme that can hydrolyze S-adenosyl-L-homocysteine (SAH) and S
methyl-5'-thioadenosine (MTA) to give S-ribosyl-L-homocysteine (SRH) and S-methyl
5'-thioribose (MTR), respectively. This reaction plays a key role in several
metabolic pathways, including biological methylation, polyamine biosynthesis,
methionine recycling and bacterial quorum sensing. Structurally, MtaN belongs to
the MtnN subfamily of the purine nucleoside phosphorylase (PNP)/uridine
phosphorylase (UDP) phosphorylase family. Aeromonas hydrophila has two MtnN
subfamily proteins: MtaN-1, a periplasmic protein with an N-terminal signal
sequence, and MtaN-2, a cytosolic protein. In this study, MtaN-1 from Aeromonas
hydrophila was successfully expressed and purified using Ni-NTA affinity, Q anion
exchange and gel-filtration chromatography. Crystals of the protein in complex
with the substrate SAH were obtained and diffracted to a resolution of 1.4 A. The
crystals belonged to the trigonal space group P3121 or P3221, with unit-cell
parameters a = b = 102.7, c = 118.8 A. The asymmetric unit contained two
molecules of MtaN-1 complexed with SAH.
PMID- 25849498
TI - Crystallization and preliminary X-ray diffraction analysis of an endo-1,4-beta-D
glucanase from Aspergillus aculeatus F-50.
AB - Cellulose is the most abundant renewable biomass on earth, and its decomposition
has proven to be very useful in a wide variety of industries. Endo-1,4-beta-D
glucanase (EC 3.2.1.4; endoglucanase), which can catalyze the random hydrolysis
of beta-1,4-glycosidic bonds to cleave cellulose into smaller fragments, is a key
cellulolytic enzyme. An endoglucanase isolated from Aspergillus aculeatus F-50
(FI-CMCase) that was classified into glycoside hydrolase family 12 has been found
to be effectively expressed in the industrial strain Pichia pastoris. Here,
recombinant FI-CMCase was crystallized. Crystals belonging to the orthorhombic
space group C2221, with unit-cell parameters a = 74.2, b = 75.1, c = 188.4 A,
were obtained by the sitting-drop vapour-diffusion method and diffracted to 1.6 A
resolution. Initial phase determination by molecular replacement clearly shows
that the crystal contains two protein molecules in the asymmetric unit. Further
model building and structure refinement are in progress.
PMID- 25849499
TI - Purification, crystallization and preliminary X-ray analysis of the periplasmic
haem-binding protein HutB from Vibrio cholerae.
AB - The mechanism of haem transport across the inner membrane of pathogenic bacteria
is currently insufficiently understood at the molecular level and no information
is available for this process in Vibrio cholerae. To obtain structural insights
into the periplasmic haem-binding protein HutB from V. cholerae (VcHutB), which
is involved in haem transport through the HutBCD haem-transport system, at the
atomic level, VcHutB was cloned, overexpressed and crystallized using 1.6 M
ammonium sulfate as a precipitant at pH 7.0. X-ray diffraction data were
collected to 2.4 A resolution on the RRCAT PX-BL-21 beamline at the Indus-2
synchrotron, Indore, India. The crystals belonged to space group P43212, with
unit-cell parameters a = b = 62.88, c = 135.8 A. Matthews coefficient
calculations indicated the presence of one monomer in the asymmetric unit, with
an approximate solvent content of 45.02%. Molecular-replacement calculations with
Phaser confirmed the presence of a monomer in the asymmetric unit.
PMID- 25849500
TI - Crystallization of mutants of Turnip yellow mosaic virus protease/ubiquitin
hydrolase designed to prevent protease self-recognition.
AB - Processing of the polyprotein of Turnip yellow mosaic virus is mediated by the
protease PRO. PRO cleaves at two places, one of which is at the C-terminus of the
PRO domain of another polyprotein molecule. In addition to this processing
activity, PRO possesses an ubiquitin hydrolase (DUB) activity. The crystal
structure of PRO has previously been reported in its polyprotein-processing mode
with the C-terminus of one PRO inserted into the catalytic site of the next PRO,
generating PRO polymers in the crystal packing of the trigonal space group. Here,
two mutants designed to disrupt specific PRO-PRO interactions were generated,
produced and purified. Crystalline plates were obtained by seeding and cross
seeding from initial 'sea urchin'-like microcrystals of one mutant. The plates
diffracted to beyond 2 A resolution at a synchrotron source and complete data
sets were collected for the two mutants. Data processing and analysis indicated
that both mutant crystals belonged to the same monoclinic space group, with two
molecules of PRO in the asymmetric unit.
PMID- 25849501
TI - Cloning, expression, crystallization and preliminary X-ray studies of a
superfolder GFP fusion of cyanobacterial Psb32.
AB - A fusion of Psb32 from the thermophilic cyanobacterium Thermosynechococcus
elongatus BP-1 (TePsb32) with superfolder GFP was created for enhanced solubility
and improved detection and purification. The fusion protein readily formed large
hexagonal crystals belonging to space group P6122. A full data set extending to
2.3 A resolution was collected at the Swiss Light Source. The phase problem could
be solved by using only the sfGFP fusion partner or by using GFP and AtTLP18.3
from Arabidopsis thaliana as search models. Based on this expression construct, a
versatile library of 24 vectors combining four different superfolder GFP variants
and three affinity tags was generated to facilitate expression and screening of
fluorescent fusion proteins.
PMID- 25849502
TI - Crystallization and preliminary X-ray characterization of the eukaryotic
replication terminator Reb1-Ter DNA complex.
AB - The Reb1 protein from Schizosaccharomyces pombe is a member of a family of
proteins that control programmed replication termination and/or transcription
termination in eukaryotic cells. These events occur at naturally occurring
replication fork barriers (RFBs), where Reb1 binds to termination (Ter) DNA sites
and coordinates the polar arrest of replication forks and transcription
approaching in opposite directions. The Reb1 DNA-binding and replication
termination domain was expressed in Escherichia coli, purified and crystallized
in complex with a 26-mer DNA Ter site. Batch crystallization under oil was
required to produce crystals of good quality for data collection. Crystals grew
in space group P21, with unit-cell parameters a = 68.9, b = 162.9, c = 71.1 A,
beta = 94.7 degrees . The crystals diffracted to a resolution of 3.0 A. The
crystals were mosaic and required two or three cycles of annealing. This study is
the first to yield structural information about this important family of proteins
and will provide insights into the mechanism of replication and transcription
termination.
PMID- 25849503
TI - Structure of the omalizumab Fab.
AB - Omalizumab is a humanized anti-IgE antibody that inhibits the binding of IgE to
its receptors on mast cells and basophils, thus blocking the IgE-mediated release
of inflammatory mediators from these cells. Omalizumab binds to the Fc domains of
IgE in proximity to the binding site of the high-affinity IgE receptor FcERI, but
the epitope and the mechanisms and conformations governing the recognition remain
unknown. In order to elucidate the molecular mechanism of its anti-IgE activity,
the aim was to analyse the interaction of omalizumab with human IgE. Therefore,
IgE Fc CE2-4 was recombinantly produced in mammalian HEK-293 cells. Functionality
of the IgE Fc was proven by ELISA and mediator-release assays. Omalizumab IgG was
cleaved with papain and the resulting Fab was purified by ion-exchange
chromatography. The complex of IgE Fc with omalizumab was prepared by size
exclusion chromatography. However, crystals containing the complex were not
obtained, suggesting that the process of crystallization favoured the
dissociation of the two proteins. Instead, two structures of the omalizumab Fab
with maximum resolutions of 1.9 and 3.0 A were obtained. The structures reveal
the arrangement of the CDRs and the position of omalizumab residues known from
prior functional studies to be involved in IgE binding. Thus, the structure of
omalizumab provides the structural basis for understanding the function of
omalizumab, allows optimization of the procedure for complex crystallization and
poses questions about the conformational requirements for anti-IgE activity.
PMID- 25849504
TI - Expression, purification, crystallization and preliminary crystallographic
analysis of a GH20 beta-N-acetylglucosaminidase from the marine bacterium Vibrio
harveyi.
AB - Vibrio harveyi beta-N-acetylglucosaminidase (VhGlcNAcase) is a new member of the
GH20 glycoside hydrolase family responsible for the complete degradation of
chitin fragments, with N-acetylglucosamine (GlcNAc) monomers as the final
products. In this study, the crystallization and preliminary crystallographic
data of wild-type VhGlcNAcase and its catalytically inactive mutant D437A in the
absence and the presence of substrate are reported. Crystals of wild-type
VhGlcNAcase were grown in 0.1 M sodium acetate pH 4.6, 1.4 M sodium malonate,
while crystals of the D437A mutant were obtained in 0.1 M bis-tris pH 7.5, 0.1 M
sodium acetate, 20% PEG 3350. X-ray data from the wild-type and the mutant
crystals were collected at a synchrotron-radiation light source and were complete
to a resolution of 2.5 A. All crystals were composed of the same type of dimer,
with the substrate N,N'-diacetylglucosamine (GlcNAc2 or diNAG) used for soaking
was cleaved by the active enzyme, leaving only a single GlcNAc molecule bound to
the protein.
PMID- 25849505
TI - Purification, crystallization and preliminary X-ray crystallographic analysis of
the phosphatase domain (PA3346PD) of the response regulator PA3346 from
Pseudomonas aeruginosa PAO1.
AB - The phosphatase domain (PA3346PD) of the response regulator PA3346 modulates the
downstream anti-anti-sigma factor PA3347 to regulate swarming motility in
Pseudomonas aeruginosa PAO1. PA3346PD, which comprises the protein phosphatase 2C
domain (PP2C), is classified as a Ser/Thr phosphatase of the Mg(2+)- or Mn(2+)
dependent protein phosphatase (PPM) family. The recombinant PA3346PD, with
molecular mass 26 kDa, was overexpressed in Escherichia coli, purified on an
Ni(2+)-NTA agarose column and crystallized by the sitting-drop vapour-diffusion
method. X-ray diffraction data were collected from PA3346PD crystals to a
resolution of 2.58 A and the crystals belonged to space group I4132 or I4332,
with unit-cell parameter a = 157.61 A. Preliminary analysis indicates the
presence of a monomer of PA3346PD in the asymmetric unit with a solvent content
of 58.4%.
PMID- 25849506
TI - Complex assembly, crystallization and preliminary X-ray crystallographic analysis
of the human Rod-Zwilch-ZW10 (RZZ) complex.
AB - The spindle-assembly checkpoint (SAC) monitors kinetochore-microtubule attachment
during mitosis. In metazoans, the three-subunit Rod-Zwilch-ZW10 (RZZ) complex is
a crucial SAC component that interacts with additional SAC-activating and SAC
silencing components, including the Mad1-Mad2 complex and cytoplasmic dynein. The
RZZ complex contains two copies of each subunit and has a predicted molecular
mass of ~800 kDa. Given the low abundance of the RZZ complex in natural sources,
its recombinant reconstitution was attempted by co-expression of its subunits in
insect cells. The RZZ complex was purified to homogeneity and subjected to
systematic crystallization attempts. Initial crystals containing the entire RZZ
complex were obtained using the sitting-drop method and were subjected to
optimization to improve the diffraction resolution limit. The crystals belonged
to space group P31 (No. 144) or P32 (No. 145), with unit-cell parameters a = b =
215.45, c = 458.7 A, alpha = beta = 90.0, gamma = 120.0 degrees .
PMID- 25849507
TI - Structure of the ABL2/ARG kinase in complex with dasatinib.
AB - ABL2/ARG (ABL-related gene) belongs to the ABL (Abelson tyrosine-protein kinase)
family of tyrosine kinases. ARG plays important roles in cell morphogenesis,
motility, growth and survival, and many of these biological roles overlap with
the cellular functions of the ABL kinase. Chronic myeloid leukemia (CML) is
associated with constitutive ABL kinase activation resulting from fusion between
parts of the breakpoint cluster region (BCR) and ABL1 genes. Similarly, fusion of
the ETV6 (Tel) and ARG genes drives some forms of T-cell acute lymphoblastic
leukemia (T-ALL) and acute myeloid leukemia (AML). Dasatinib is a tyrosine kinase
inhibitor used for the treatment of CML by inhibiting ABL, and while it also
inhibits ARG, there is currently no structure of ARG in complex with dasatinib.
Here, the co-crystal structure of the mouse ARG catalytic domain with dasatinib
at 2.5 A resolution is reported. Dasatinib-bound ARG is found in the DFG-in
conformation although it is nonphosphorylated on the activation-loop tyrosine. In
this structure the glycine-rich P-loop is found in a relatively open conformation
compared with other known ABL family-inhibitor complex structures.
PMID- 25849508
TI - Structure of dihydrodipicolinate synthase from the commensal bacterium
Bacteroides thetaiotaomicron at 2.1 A resolution.
AB - Dihydrodipicolinate synthase (DapA) catalyzes the first committed step of the
diaminopimelate biosynthetic pathway of lysine. It has been shown to be an
essential enzyme in many bacteria and has been the subject of research to
generate novel antibiotics. However, this pathway is present in both pathogenic
and commensal bacteria, and antibiotics targeting DapA may interfere with normal
gut colonization. Bacteroides thetaiotaomicron is a Gram-negative commensal
bacterium that makes up a large proportion of the normal microbiota of the human
gut. The structure of DapA from B. thetaiotaomicron (BtDapA) has been determined.
This structure will help to guide the generation of selectively active antibiotic
compounds targeting DapA.
PMID- 25849509
TI - Analytical ultracentrifugation and preliminary X-ray studies of the chloroplast
envelope quinone oxidoreductase homologue from Arabidopsis thaliana.
AB - Quinone oxidoreductases reduce a broad range of quinones and are widely
distributed among living organisms. The chloroplast envelope quinone
oxidoreductase homologue (ceQORH) from Arabidopsis thaliana binds NADPH, lacks a
classical N-terminal and cleavable chloroplast transit peptide, and is
transported through the chloroplast envelope membrane by an unknown alternative
pathway without cleavage of its internal chloroplast targeting sequence. To
unravel the fold of this targeting sequence and its substrate specificity, ceQORH
from A. thaliana was overexpressed in Escherichia coli, purified and
crystallized. Crystals of apo ceQORH were obtained and a complete data set was
collected at 2.34 A resolution. The crystals belonged to space group C2221, with
two molecules in the asymmetric unit.
PMID- 25849510
TI - Crystallization and preliminary X-ray analysis of four cysteine proteases from
Ficus carica latex.
AB - The latex of the common fig (Ficus carica) contains a mixture of at least five
cysteine proteases commonly known as ficins (EC 3.4.22.3). Four of these
proteases were purified to homogeneity and crystals were obtained in a variety of
conditions. The four ficin (iso)forms appear in ten different crystal forms. All
diffracted to better than 2.10 A resolution and for each form at least one
crystal form diffracted to 1.60 A resolution or higher. Ficin (iso)forms B and C
share a common crystal form, suggesting close sequence and structural similarity.
The latter diffracted to a resolution of 1.20 A and belonged to space group P3121
or P3221, with unit-cell parameters a = b = 88.9, c = 55.9 A.
PMID- 25849511
TI - Cloning, expression, purification, crystallization and preliminary X-ray
diffraction analysis of AerF from Microcystis aeruginosa, a putative reductase
participating in aeruginosin biosynthesis.
AB - The 2-carboxy-6-hydroxyoctahydroindole moiety is an essential residue for the
antithrombotic activity of aeruginosins, which are a class of cyanobacteria
derived bioactive linear tetrapeptides. The biosynthetic pathway of the 2-carboxy
6-hydroxyoctahydroindole moiety has not yet been resolved. AerF was indicated to
be involved in the biosynthesis of the 2-carboxy-6-hydroxyoctahydroindole moiety.
This study reports the cloning, expression, purification, crystallization and
preliminary X-ray diffraction analysis of AerF from Microcystis aeruginosa with a
C-terminal His6 tag. The crystal diffracted to a maximum resolution of 1.38 A and
belonged to the tetragonal space group P4322, with unit-cell parameters a = b =
101.581, c = 116.094 A. The calculated Matthews coefficient and solvent content
of the crystal were 2.47 A(3) Da(-1) and 50.32%, respectively. The initial model
of the structure was obtained by the molecular-replacement method and refinement
of the structure is in progress.
PMID- 25849512
TI - Serendipitous crystallization and structure determination of cyanase (CynS) from
Serratia proteamaculans.
AB - Cyanate hydratase (CynS) catalyzes the decomposition of cyanate and bicarbonate
into ammonia and carbon dioxide. Here, the serendipitous crystallization of CynS
from Serratia proteamaculans (SpCynS) is reported. SpCynS was crystallized as an
impurity and its identity was determined using mass-spectrometric analysis. The
crystals belonged to space group P1 and diffracted to 2.1 A resolution. The
overall structure of SpCynS is very similar to a previously determined structure
of CynS from Escherichia coli. Density for a ligand bound to the SpCynS active
site was observed, but could not be unambiguously identified. Additionally,
glycerol molecules bound at the entry to the active site of the enzyme indicate
conserved residues that might be important for the trafficking of substrates and
products.
PMID- 25849513
TI - Expression, purification, crystallization and preliminary X-ray diffraction
analysis of a type II NADH:quinone oxidoreductase from the human pathogen
Staphylococcus aureus.
AB - In recent years, type II NADH dehydrogenases (NDH-IIs) have emerged as potential
drug targets for a wide range of human disease causative agents. In this work,
the NDH-II enzyme from the Gram-positive human pathogen Staphylococcus aureus was
recombinantly expressed in Escherichia coli, purified, crystallized and a
crystallographic data set was collected at a wavelength of 0.873 A. The crystals
belonged to the orthorhombic space group P212121, with unit-cell parameters a =
81.8, b = 86.0, c = 269.9 A, contained four monomers per asymmetric unit and
diffracted to a resolution of 3.32 A. A molecular-replacement solution was
obtained and model building and refinement are currently under way.
PMID- 25849514
TI - Tobacco use and suicide attempt: longitudinal analysis with retrospective
reports.
AB - BACKGROUND: Suicide has been associated with smoking/tobacco use but its
association of and change in smoking/tobacco use status with suicide attempt (SA)
is not well established. METHODS: We investigated whether persistent, former
tobacco use, initiation, quitting tobacco use, relapse to tobacco use, and DSM-IV
nicotine dependence predict independently SA using Wave 1 and 2 data of the
National Epidemiologic Survey of Alcohol and Related Conditions. Data from 34,653
US adults interviewed at Wave 1 (2001-02) and Wave 2 (2004-05) were analyzed. The
main outcome measure was SA between Wave 1 and Wave 2 as reported at Wave 2.
RESULTS: Among the 1,673 respondents reporting lifetime SA at Wave 2, 328
individuals reported SA between Wave 1 and Wave 2. Current and former tobacco use
at Wave 1 predicted Wave 2 SA independently of socio-demographic characteristics,
psychiatric history, and prior SA (Adjusted Odds Ratio (AOR): 1.49; 95% CI: 1.13
1.95, AOR: 1.31; 95% CI:1.01-1.69, respectively versus never tobacco users). The
strongest association with SA was observed among former tobacco users who
relapsed after Wave 1 (AOR: 4.66; 95% CI: 3.49-6.24) and among tobacco use
initiators after Wave 1 (AOR: 3.16; 95% CI: 2.23-4.49). Persistent tobacco use
(current tobacco use at both Wave 1 and Wave 2) also had an increased risk of SA
(AOR: 1.89; 95% CI: 1.47-2.42). However, former tobacco users in both Waves 1 and
2 did not show a significantly elevated risk for SA in Wave 2 (AOR:1.09, 95% CI:
0.78-1.52) suggesting that the risk resided mainly in Wave 1 former tobacco users
who relapsed to tobacco use by Wave 2. DSM-IV nicotine dependence did not predict
SA at Wave 2. CONCLUSION: In a representative sample of US adults, relapse,
tobacco use initiation, and persistent tobacco use, which are amenable to
intervention, were associated with risk of SA.
PMID- 25849515
TI - Elucidating the foundations of statistical inference with 2 x 2 tables.
AB - To many, the foundations of statistical inference are cryptic and irrelevant to
routine statistical practice. The analysis of 2 x 2 contingency tables,
omnipresent in the scientific literature, is a case in point. Fisher's exact test
is routinely used even though it has been fraught with controversy for over 70
years. The problem, not widely acknowledged, is that several different p-values
can be associated with a single table, making scientific inference inconsistent.
The root cause of this controversy lies in the table's origins and the manner in
which nuisance parameters are eliminated. However, fundamental statistical
principles (e.g., sufficiency, ancillarity, conditionality, and likelihood) can
shed light on the controversy and guide our approach in using this test. In this
paper, we use these fundamental principles to show how much information is lost
when the tables origins are ignored and when various approaches are used to
eliminate unknown nuisance parameters. We present novel likelihood contours to
aid in the visualization of information loss and show that the information loss
is often virtually non-existent. We find that problems arising from the
discreteness of the sample space are exacerbated by p-value-based inference.
Accordingly, methods that are less sensitive to this discreteness - likelihood
ratios, posterior probabilities and mid-p-values - lead to more consistent
inferences.
PMID- 25849516
TI - The quality of sputum smear microscopy in public-private mix directly observed
treatment laboratories in West Amhara region, Ethiopia.
AB - Ethiopia adopted Public-Private Mix Directly Observed Treatment Short Course
Chemotherapy (PPM-DOTS) strategy for tuberculosis (TB) control program. Quality
of sputum smear microscopy has paramount importance for tuberculosis control
program in resource-poor countries like Ethiopia. A cross-sectional study was
conducted to assess the quality of sputum smear microscopy in 37 Public-Private
Mix laboratories in West Amhara, Ethiopia. The three external quality assessment
methods (onsite evaluation, panel testing and blind rechecking) were employed.
Onsite assessment revealed that 67.6% of PPM-DOTS laboratories were below the
standard physical space (5 X 6) m2. The average monthly workload per laboratory
technician was 19.5 (SD+/-2.9) slides with 12.8% positivity rate. The quality of
Acid Fast Bacilli (AFB) staining reagents was sub-standard. The overall agreement
for blind rechecking of 1,123 AFB slides was 99.4% (Kappa = 0.97). Reading of 370
AFB panel slides showed 3.5% false reading (Kappa = 0.92). Moreover, the
consistency of reading scanty bacilli slides was lower (93%) compared to 1+, 2+
and 3+ bacilli. Based on blind rechecking and panel testing results, PPM-DOTS
site laboratories showed good agreement with the reference laboratory. Physical
space and qualities of AFB reagents would be areas of intervention to sustain the
quality of sputum smear microscopy. Therefore, regular external quality
assessment and provision of basic laboratory supplies for TB diagnosis would be
the way forward to improve the quality of sputum smear microscopy services in PPM
DOTS laboratories.
PMID- 25849517
TI - [Inadequate medical records system--a health risk].
PMID- 25849519
TI - [Not Available].
PMID- 25849518
TI - [Transparent teamwork necessary for safe obstetric care. Territorial thinking and
low competence resulted in healthcare scandal in the UK].
PMID- 25849521
TI - Preoperative Prognostic Factors and Predictive Score in Patients Operated On for
Combined Cataract and Idiopathic Epiretinal Membrane.
AB - PURPOSE: To report preoperative prognostic factors associated with visual acuity
recovery 1 year after combined cataract and idiopathic epiretinal membrane (ERM)
surgery and to introduce a predictive score. DESIGN: Interventional case series
and estimation of a predictive score. METHODS: One hundred forty-two patients (1
eye per patient) operated on for combined cataract and idiopathic ERM in the
University Hospital of Dijon were followed for 12 months. Preoperative clinical
features and spectral-domain optical coherence tomography (OCT) parameters were
compared between eyes that recovered >=20/20 final best-corrected visual acuity
(BCVA) and those with <20/20 final BCVA. Multivariate analysis and predictive
score were provided. RESULTS: At 12 months, 60 eyes (42%) recovered >=20/20 BCVA
and 82 (58%) had lower visual results. Logistic regression analysis showed that
final BCVA was associated with age (P = .040), duration of symptoms (P = .025),
initial BCVA (P = .002), and inner and outer segment (IS/OS) junction disruption
on spectral-domain OCT (P = .010). The preoperative 10-point predictive score
including these parameters reached 82% sensitivity and 66% specificity. With a
score >5, patients had a >=56% chance of recovering 20/20 final BCVA instead of
<=27% when the score was <=5. CONCLUSIONS: Age, duration of symptoms, and initial
BCVA appear to be reliable prognostic factors in patients undergoing combined
cataract and idiopathic ERM surgery. Combining these factors with analysis of the
IS/OS junction provides a predictive score to estimate individual chances of good
visual outcome.
PMID- 25849520
TI - Quantitative Trait Locus Analysis of SIX1-SIX6 With Retinal Nerve Fiber Layer
Thickness in Individuals of European Descent.
AB - PURPOSE: To perform a quantitative trait locus (QTL) analysis and evaluate
whether a locus between SIX1 and SIX6 is associated with retinal nerve fiber
layer (RNFL) thickness in individuals of European descent. DESIGN: Observational,
multicenter, cross-sectional study. METHODS: A total of 231 participants were
recruited from the Diagnostic Innovations in Glaucoma Study and the African
Descent and Glaucoma Evaluation Study. Association of rs10483727 in SIX1-SIX6
with global and sectoral RNFL thickness was performed. Quantitative trait
analysis with the additive model of inheritance was analyzed using linear
regression. Trend analysis was performed to evaluate the mean global and sectoral
RNFL thickness with 3 genotypes of interest (T/T, C/T, C/C). All models were
adjusted for age and sex. RESULTS: Direction of association between T allele and
RNFL thickness was consistent in the global and different sectoral RNFL regions.
Each copy of the T risk allele in rs10483727 was associated with -0.16 MUm
thinner global RNFL thickness (beta = -0.16, 95% confidence interval: -0.28 to
0.03; P = .01). Similar patterns were found for the sectoral regions, including
inferior (P = .03), inferior-nasal (P = .017), superior-nasal (P = .0025),
superior (P = .002) and superior-temporal (P = .008). The greatest differences
were observed in the superior and inferior quadrants, supporting clinical
observations for RNFL thinning in glaucoma. Thinner global RNFL was found in
subjects with T/T genotypes compared to subjects with C/T and C/C genotypes (P =
.044). CONCLUSIONS: Each copy of the T risk allele has an additive effect and was
associated with thinner global and sectoral RNFL. Findings from this QTL analysis
further support a genetic contribution to glaucoma pathophysiology.
PMID- 25849522
TI - Spectrum of Retinal Vascular Diseases Associated With Paracentral Acute Middle
Maculopathy.
AB - PURPOSE: To evaluate the spectrum of retinal diseases that can demonstrate
paracentral acute middle maculopathy and isolated ischemia of the intermediate
and deep capillary plexus. DESIGN: Retrospective, multicenter, observational case
series. METHODS: This is a retrospective case series review of 9 patients (10
eyes) from 5 centers with paracentral acute middle maculopathy lesions and
previously unreported retinal vascular etiologies. Case presentations and
multimodal imaging, including color photographs, near-infrared reflectance,
fluorescein angiography, spectral-domain optical coherence tomography (SD OCT),
and orbital color Doppler imaging, are described. Baseline and follow-up findings
are correlated with clinical presentation, demographics, and systemic
associations. RESULTS: Five men and 4 women, aged 27-66 years, were included.
Isolated band-like hyperreflective lesions in the middle retinal layers,
otherwise known as paracentral acute middle maculopathy, were observed in all
patients at baseline presentation. Follow-up SD OCT analysis of these paracentral
acute middle maculopathy lesions demonstrated subsequent thinning of the inner
nuclear layer. Novel retinal vascular associations leading to retinal
vasculopathy and paracentral acute middle maculopathy include eye compression
injury causing global ocular ischemia, sickle cell crisis, Purtscher's
retinopathy, inflammatory occlusive retinal vasculitis, post-H1N1 vaccine,
hypertensive retinopathy, migraine disorder, and post-upper respiratory
infection. CONCLUSION: Paracentral acute middle maculopathy lesions may develop
in a wide spectrum of retinal vascular diseases. They are best identified with SD
OCT analysis and may represent ischemia of the intermediate and deep capillary
plexus. These lesions typically result in permanent thinning of the inner nuclear
layer and are critical to identify in order to determine the cause of unexplained
vision loss.
PMID- 25849524
TI - Explaining the appeal for immigrant men who have sex with men of a community
based rapid HIV-testing site in Montreal (Actuel sur Rue).
AB - Immigrant men who have sex with men (MSM) are vulnerable to HIV. In the last
decade, several rapid HIV-testing facilities targeting MSM have been established
around the world and seem popular among immigrants. This study analyzes factors
contributing to immigrant MSM's use of Actuel sur Rue (AsR), a community-based
rapid HIV-testing site in Montreal's gay village, where 31% of clients are
immigrants. From October 2013 to January 2014, AsR staff compiled a list of new
clients born outside of Canada. With their consent, 40 immigrant MSM were reached
among these new clients for a 15-minute phone survey entailing open-ended and
multiple-choice questions. The survey sought immigrant MSM's reasons for visiting
AsR; satisfaction with service and staff; and open comments. An inductive
thematic analysis was conducted with the qualitative data, and descriptive
statistics were produced with the quantitative data. The qualitative findings
indicate that the main reasons for seeking an HIV test were a recent risk,
routine testing, or being in a new relationship. Clients chose AsR mainly because
it is easily accessible, service is fast or they heard about it from a friend.
The quantitative findings indicate that rates of satisfaction were high (over 90%
were satisfied about all aspects except for openings hours) and more than 80%
felt comfortable while receiving services at AsR. Nevertheless, this study's
findings have implications for improving services. They stress the importance of
offering rapid yet comprehensive service and of taking into account immigrant
MSM's concerns for confidentiality.
PMID- 25849523
TI - The effectiveness of lifestyle triple P in the Netherlands: a randomized
controlled trial.
AB - INTRODUCTION: Lifestyle Triple P is a general parenting intervention which
focuses on preventing further excessive weight gain in overweight and obese
children. The objective of the current study was to assess the effectiveness of
the Lifestyle Triple P intervention in the Netherlands. METHOD: We used a
parallel randomized controlled design to test the effectiveness of the
intervention. In total, 86 child-parent triads (children 4-8 years old,
overweight or obese) were recruited and randomly assigned (allocation ratio 1:1)
to the Lifestyle Triple P intervention or the control condition. Parents in the
intervention condition received a 14-week intervention consisting of ten 90
minute group sessions and four individual telephone sessions. Primary outcome
measure was the children's body composition (BMI z-scores, waist circumference
and skinfolds). The research assistant who performed the measurements was blinded
for group assignment. Secondary outcome measures were the children's dietary
behavior and physical activity level, parenting practices, parental feeding
style, parenting style, and parental self-efficacy. Outcome measures were
assessed at baseline and 4 months (short-term) and 12 months (long-term) after
baseline. Multilevel multiple regression analyses were conducted to determine the
effect of the intervention on primary and secondary outcome measures. RESULTS: No
intervention effects were found on children's body composition. Analyses of
secondary outcomes showed positive short-term intervention effects on children's
soft-drink consumption and parental responsibility regarding physical activity,
encouragement to eat, psychological control, and efficacy and satisfaction with
parenting. Longer-term intervention effects were found on parent's report of
children's time spent on sedentary behavior and playing outside, parental
monitoring food intake, and responsibility regarding nutrition. CONCLUSION:
Although the Lifestyle Triple P intervention showed positive effects on some
parent reported child behaviors and parenting measures, no effects were visible
on children's body composition or objectively measured physical activity. Several
adjustments of the intervention content are recommended, for example including a
booster session. TRIAL REGISTRATION: Nederlands Trial Register NTR 2555.
PMID- 25849525
TI - Activation of cannabinoid CB2 receptors reduces hyperalgesia in an experimental
autoimmune encephalomyelitis mouse model of multiple sclerosis.
AB - Clinical trials investigating the analgesic efficacy of cannabinoids in multiple
sclerosis have yielded mixed results, possibly due to psychotropic side effects
mediated by cannabinoid CB1 receptors. We hypothesized that, a CB2-specific
agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune
encephalomyelitis mouse model of multiple sclerosis. Four weeks after induction
of experimental autoimmune encephalomyelitis, we found that intrathecal
administration of JWH-133 (10-100MUg) dose-dependently reduced both mechanical
and cold hypersensitivity without producing signs of sedation or ataxia. The anti
hyperalgesic effects of JWH-133 could be dose-dependently prevented by
intrathecal co-administration of the CB2 antagonist, AM-630 (1-3MUg). Our results
suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of
the spinal cord, to suppress the hypersensitivity associated with experimental
autoimmune encephalomyelitis. These are the first pre-clinical studies to
directly promote CB2 as a promising target for the treatment of central pain in
an animal model of multiple sclerosis.
PMID- 25849526
TI - A novel brain-derived neurotrophic factor-modulating peptide attenuates Abeta1-42
induced neurotoxicity in vitro.
AB - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family,
which plays important roles in learning and memory formation and in protecting
neurons from diverse neurotoxic insults, such as amyloid-beta (Abeta). Since BDNF
expression is decreased in patients with Alzheimer's disease, various strategies
have attempted to increase BDNF levels. In a previous study, we screened and
identified a novel BDNF-modulating peptide (consisting of methionine-valine
glycine, named Neuropep-1) by a positional scanning-synthetic peptide
combinatorial library (PS-SPCL). Neuropep-1 exhibited neuroprotective effects
against in vitro and in vivo Alzheimer's disease models. Based on the previous PS
SPCL data, we modified the amino acid sequence of Neuropep-1 in this study to
identify a more potent novel BDNF-modulating peptide. By replacing the valine in
the second position with aspartic acid, the resulting Neuropep-4 was found to be
highly effective in inducing BDNF expression even at concentrations of 1pM in the
SH-SY5Y cell line and rat primary cortical neurons. In addition, among the tested
peptides, Neuropep-4 provided neurons with the strongest protection against
oligomeric and/or fibrillar Abeta1-42-induced cell death through BDNF
upregulation. These results suggest the potential of Neuropep-4 as a therapeutic
candidate for treating neurodegenerative diseases, such as AD.
PMID- 25849527
TI - Neurological soft signs in primary headache patients.
AB - Neurological soft signs (NSS) are semeiotic anomalies not assessed by the
standard neurological examination, primarily developed in psychiatric settings
and recently proposed as potential markers of minor brain circuit alterations,
especially the cerebellar-thalamic-prefrontal network. Primary headache patients
present with normal neurological examination and frequent psychiatric
comorbidity. Aim of this exploratory study consisted in assessing NSS in 20
episodic frequent migraine (MH) and in 10 tension-type headache (ETTH)
outpatients compared to 30 matched healthy controls. NSS were assessed by the
Heidelberg scale; clinical characteristics and brain MRI were additionally
obtained in all patients. NSS were increased by ~70 and ~90% in ETTH and MH,
respectively, with respect to controls (p<0.001) and the difference remained
significant even after controlling for age and education. Headache type and
characteristics did not influence NSS presentation, while headache patients with
white matter hyperintensities (WMH) at brain MRI had higher NSS scores compared
both to normal controls and patients without WMH. NSS identify a subset of
primary headache patients sharing the same comorbidities or minimal brain
anomalies, suggesting that tailored prophylactic options might apply.
PMID- 25849528
TI - Coarse topographic organization of pheromone-sensitive afferents from different
antennal surfaces in the American cockroach.
AB - In contrast to visual, auditory, taste, and mechanosensory neuropils, in which
sensory afferents are topographically organized on the basis of their peripheral
soma locations, axons of cognate sensory neurons from different locations of the
olfactory sense organ converge onto a small spherical neuropil (glomerulus) in
the first-order olfactory center. In the cockroach Periplaneta americana, sex
pheromone-sensitive afferents with somata in the antero-dorsal and postero
ventral surfaces of a long whip-like antenna are biased toward the anterior and
posterior regions of a macroglomerulus, respectively. In each region, afferents
with somata in the more proximal antenna project to more proximal region,
relative to the axonal entry points. However, precise topography of afferents in
the macroglomerulus has remained unknown. Using single and multiple neuronal
stainings, we showed that afferents arising from anterior, dorsal, ventral and
posterior surfaces of the proximal regions of an antenna were biased
progressively from the anterior to posterior region of the macroglomerulus,
reflecting chiasmatic axonal re-arrangements that occur immediately before
entering the antennal lobe. Morphologies of individual afferents originating from
the proximal antenna matched results of mass neuronal stainings, but their three
dimensional origins in the antenna were hardly predictable on the basis of the
projection patterns. Such projection biases made by neuronal populations differ
from strict somatotopic projections of antennal mechanosensory neurons in the
same species, suggesting a unique sensory mechanism to process information about
odor location and direction on a single antenna.
PMID- 25849529
TI - Effects of 1,8-cineole on Na(+) currents of dissociated superior cervical ganglia
neurons.
AB - 1,8-Cineole is a terpenoid present in many essential oil of plants with several
pharmacological and biological effects, including antinociceptive, smooth muscle
relaxant and ion channel activation. Also, 1,8-cineole blocked action potentials,
reducing excitability of peripheral neurons. The objective of this work was to
investigate effects of 1,8-cineole on Na(+) currents (INa(+)) in dissociated
superior cervical ganglion neurons (SCG). Wistar rats of both sexes were used (10
12 weeks old, 200-300g). SCG's were dissected and neurons were enzymatically
treated. To study 1,8-cineole effect on INa(+), the patch-clamp technique in
whole-cell mode was employed. 1,8-Cineole (6.0mM) partially blocked INa(+) in SCG
neurons. The effect stabilized within ~150s and there was a partial recovery of
INa(+) after washout. Current density was reduced from -105.8 to -83.7pA/pF,
corresponding to a decrease to ~20% of control. 1,8-Cineole also reduced the time
to-peak of INa(+) activation and the amplitude and decay time constants of INa(+)
inactivation. Current-voltage plots revealed that 1,8-cineole left-shifted the
V1/2 of both activation and inactivation curves by ~10 and ~20mV, respectively.
In conclusion, we demonstrate that 1,8-cineole directly affects Na(+) channels of
the SCG by modifying several gating parameters that are likely to be the major
cause of excitability blockade.
PMID- 25849530
TI - Continuous control of the nonlinearity phase for harmonic generations.
AB - The capability of locally engineering the nonlinear optical properties of media
is crucial in nonlinear optics. Although poling is the most widely employed
technique for achieving locally controlled nonlinearity, it leads only to a
binary nonlinear state, which is equivalent to a discrete phase change of pi in
the nonlinear polarizability. Here, inspired by the concept of spin-rotation
coupling, we experimentally demonstrate nonlinear metasurfaces with homogeneous
linear optical properties but spatially varying effective nonlinear
polarizability with continuously controllable phase. The continuous phase control
over the local nonlinearity is demonstrated for second and third harmonic
generation by using nonlinear metasurfaces consisting of nanoantennas of C3 and
C4 rotational symmetries, respectively. The continuous phase engineering of the
effective nonlinear polarizability enables complete control over the propagation
of harmonic generation signals. Therefore, this method seamlessly combines the
generation and manipulation of harmonic waves, paving the way for highly compact
nonlinear nanophotonic devices.
PMID- 25849531
TI - Enhancement of the chemical stability in confined delta-Bi2O3.
AB - Bismuth-oxide-based materials are the building blocks for modern ferroelectrics,
multiferroics, gas sensors, light photocatalysts and fuel cells. Although the
cubic fluorite delta-phase of bismuth oxide (delta-Bi2O3) exhibits the highest
conductivity of known solid-state oxygen ion conductors, its instability prevents
use at low temperature. Here we demonstrate the possibility of stabilizing delta
Bi2O3 using highly coherent interfaces of alternating layers of Er2O3-stabilized
delta-Bi2O3 and Gd2O3-doped CeO2. Remarkably, an exceptionally high chemical
stability in reducing conditions and redox cycles at high temperature, usually
unattainable for Bi2O3-based materials, is achieved. Even more interestingly, at
low oxygen partial pressure the layered material shows anomalous high
conductivity, equal or superior to pure delta-Bi2O3 in air. This suggests a
strategy to design and stabilize new materials that are comprised of
intrinsically unstable but high-performing component materials.
PMID- 25849532
TI - Lead halide perovskite nanowire lasers with low lasing thresholds and high
quality factors.
AB - The remarkable performance of lead halide perovskites in solar cells can be
attributed to the long carrier lifetimes and low non-radiative recombination
rates, the same physical properties that are ideal for semiconductor lasers.
Here, we show room-temperature and wavelength-tunable lasing from single-crystal
lead halide perovskite nanowires with very low lasing thresholds (220 nJ cm(-2))
and high quality factors (Q ~ 3,600). The lasing threshold corresponds to a
charge carrier density as low as 1.5 * 10(16) cm(-3). Kinetic analysis based on
time-resolved fluorescence reveals little charge carrier trapping in these single
crystal nanowires and gives estimated lasing quantum yields approaching 100%.
Such lasing performance, coupled with the facile solution growth of single
crystal nanowires and the broad stoichiometry-dependent tunability of emission
colour, makes lead halide perovskites ideal materials for the development of
nanophotonics, in parallel with the rapid development in photovoltaics from the
same materials.
PMID- 25849533
TI - Aberrant fat metabolism in Caenorhabditis elegans mutants with defects in the
defecation motor program.
AB - The molecular mechanisms by which dietary fatty acids are absorbed by the
intestine, and the way in which the process is regulated are poorly understood.
In a genetic screen for mutations affecting fat accumulation in the intestine of
Caenorhabditis elegans, nematode worms, we have isolated mutations in the aex-5
gene, which encodes a Kex2/subtilisin-family, Ca2+-sensitive proprotein
convertase known to be required for maturation of certain neuropeptides, and for
a discrete step in an ultradian rhythmic phenomenon called the defecation motor
program. We demonstrate that aex-5 mutants have markedly lower steady-state
levels of fat in the intestine, and that this defect is associated with a
significant reduction in the rate at which labeled fatty acid derivatives are
taken up from the intestinal lumen. Other mutations affecting the defecation
motor program also affect steady-state levels of triglycerides, suggesting that
the program is required per se for the proper accumulation of neutral lipids. Our
results suggest that an important function of the defecation motor program in C.
elegans is to promote the uptake of an important class of dietary nutrients. They
also imply that modulation of the program might be one way in which worms adjust
nutrient uptake in response to altered metabolic status.
PMID- 25849534
TI - Predictability of road traffic and congestion in urban areas.
AB - Mitigating traffic congestion on urban roads, with paramount importance in urban
development and reduction of energy consumption and air pollution, depends on our
ability to foresee road usage and traffic conditions pertaining to the collective
behavior of drivers, raising a significant question: to what degree is road
traffic predictable in urban areas? Here we rely on the precise records of daily
vehicle mobility based on GPS positioning device installed in taxis to uncover
the potential daily predictability of urban traffic patterns. Using the mapping
from the degree of congestion on roads into a time series of symbols and
measuring its entropy, we find a relatively high daily predictability of traffic
conditions despite the absence of any priori knowledge of drivers' origins and
destinations and quite different travel patterns between weekdays and weekends.
Moreover, we find a counterintuitive dependence of the predictability on travel
speed: the road segment associated with intermediate average travel speed is most
difficult to be predicted. We also explore the possibility of recovering the
traffic condition of an inaccessible segment from its adjacent segments with
respect to limited observability. The highly predictable traffic patterns in
spite of the heterogeneity of drivers' behaviors and the variability of their
origins and destinations enables development of accurate predictive models for
eventually devising practical strategies to mitigate urban road congestion.
PMID- 25849535
TI - Tonsillectomy and the risk for deep neck infection-a nationwide cohort study.
AB - BACKGROUND: Although the tonsils contribute to first line immunity against
foreign pathogens in the upper aero-digestive tract, the association of
tonsillectomy with the risk of deep neck infection remains unclear. The aim of
this study was to assess the incidence rate and risk of deep neck infection among
patients who had undergone a tonsillectomy. METHODS: This retrospective cohort
study evaluated all patients who had undergone tonsillectomy between 2001 and
2009 as identified from the Taiwan National Health Insurance Research Database.
For each post-tonsillectomy patient, 10 age-, sex-, and index date-matched
controls without a history of tonsillectomy were randomly selected. Cox
Proportional hazard model and propensity score model were performed to evaluate
the association between tonsillectomy and deep neck infection after adjusting for
demographic and clinical data. RESULTS: There were 34 (71.6 cases per 100,000
person-years) and 174 (36.6 cases per 100,000 person-years) patients that
developed deep neck infection in the tonsillectomized and comparison cohorts,
respectively. After adjusting for covariates, patients who had undergone a
tonsillectomy had a 1.71-fold greater risk of deep neck infection by both Cox
proportional hazard model (95% confidence interval, 1.13-2.59) and propensity
score model (95% confidence interval, 1.10-2.66). This association was not
altered regardless of the indication for tonsillectomy (i.e. chronic/recurrent
tonsillitis or sleep apnea/hypertrophy of tonsil) (p = 0.9797). CONCLUSIONS:
Based on our review of a nationwide cohort study we identified that the risk of
deep neck infection is significantly increased among patients who have undergone
a tonsillectomy. Additional research is needed to explore the possible mechanisms
behind these findings.
PMID- 25849536
TI - A five-year prospective study of diabetic retinopathy progression in chinese type
2 diabetes patients with "well-controlled" blood glucose.
AB - PURPOSE: To determine the progression rate and risk factors for diabetic
retinopathy (DR) in Chinese type 2 diabetic patients who have reached the target
hemoglobin A1c (HbA1c) level recommended by the American Diabetes Association.
METHODS: This was a 5-year community-based prospective study. The study
population consisted of patients with type 2 diabetes with HbA1c less than 7.0%.
Demographic information, systemic examination results and ophthalmological test
results for each participant were collected. The outcome of this study was the
progression of DR, which was defined as an increase in DR grade in one or both
eyes at the final visit in comparison to the baseline status. The association
between each potential risk factor and DR progression was studied. RESULTS: A
total of 453 patients with HbA1c less than 7.0% were included in the study group.
In 146 patients (32.22%), DR developed or progressed during the five-year follow
up. Baseline HbA1c level was the only independent risk factor for DR progression
(p<0.01, OR = 2.84, 95%CI: 2.11~3.82). The logistic regression function suggested
that the possibility of DR progression increased fastest when baseline HbA1c
increased from 5.2% to 6.4%. The 5-year DR progression rate in patients with
baseline HbA1c less than 5.2%, between 5.2% and 6.4%, and over 6.4% were 19.62%,
24.41%, and 76.83%, respectively. CONCLUSIONS: To slow the progression of DR in
Chinese patients with type 2 diabetes, more intensive glucose control is
recommended.
PMID- 25849537
TI - Rye affects bacterial translocation, intestinal viscosity, microbiota composition
and bone mineralization in Turkey poults.
AB - Previously, we have reported that rye significantly increased both viscosity and
Clostridium perfringens proliferation when compared with corn in an in vitro
digestive model. Two independent trials were conducted to evaluate the effect of
rye as a source of energy on bacterial translocation, intestinal viscosity, gut
microbiota composition, and bone mineralization, when compared with corn in
turkey poults. In each experiment, day-of-hatch, turkey poults were randomly
assigned to either a corn or a rye diet (n = 0 /group). At 10 d of age, in both
experiments, 12 birds/group were given an oral gavage dose of fluorescein
isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood and liver
samples were collected to evaluate the passage of FITC-d and bacterial
translocation (BT) respectively. Duodenum, ileum and cecum gut sections were
collected to evaluate intestinal viscosity and to enumerate gut microbiota.
Tibias were collected for observation of bone parameters. Broilers fed with a rye
diet showed increased (p<0.05) intestinal viscosity, BT, and serum FITC-d.
Bacterial enumeration revealed that turkey poults fed with rye had increased the
number of total lactic acid bacteria (LAB) in all three sections of the
gastrointestinal tract evaluated when compared to turkey poults fed with corn.
Turkey poults fed with rye also had significantly higher coliforms in duodenum
and ileum but not in the ceca, whereas the total number of anaerobes increased
only in duodenum. A significant reduction in bone strength and bone
mineralization was observed in turkey poults fed with rye when compared with corn
fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that
increased intestinal viscosity, increased leakage through the intestinal tract,
and altered the microbiota composition and bone mineralization. Studies to
evaluate dietary inclusion of selected Direct-Fed Microbial (DFM) candidates that
produce exogenous enzymes in rye fed turkey poults are currently being evaluated.
PMID- 25849538
TI - Activation of glycoprotein VI (GPVI) and C-type lectin-like receptor-2 (CLEC-2)
underlies platelet activation by diesel exhaust particles and other
charged/hydrophobic ligands.
AB - Platelets are activated by a range of stimuli that share little or no resemblance
in structure to each other or to recognized ligands, including diesel exhaust
particles (DEP), small peptides [4N1-1, Champs (computed helical anti-membrane
proteins), LSARLAF (Leu-Ser-Ala-Arg-Leu-Ala-Phe)], proteins (histones) and large
polysaccharides (fucoidan, dextran sulfate). This miscellaneous group stimulate
aggregation of human and mouse platelets through the glycoprotein VI (GPVI)-FcR
gamma-chain complex and/or C-type lectin-like receptor-2 (CLEC-2) as shown using
platelets from mice deficient in either or both of these receptors. In addition,
all of these ligands stimulate tyrosine phosphorylation in GPVI/CLEC-2-double
deficient platelets, indicating that they bind to additional surface receptors,
although only in the case of dextran sulfate does this lead to activation. DEP,
fucoidan and dextran sulfate, but not the other agonists, activate GPVI and CLEC
2 in transfected cell lines as shown using a sensitive reporter assay confirming
a direct interaction with the two receptors. We conclude that this miscellaneous
group of ligands bind to multiple proteins on the cell surface including GPVI
and/or CLEC-2, inducing activation. These results have pathophysiological
significance in a variety of conditions that involve exposure to activating
charged/hydrophobic agents.
PMID- 25849539
TI - Exposure to airborne particles and volatile organic compounds from polyurethane
molding, spray painting, lacquering, and gluing in a workshop.
AB - Due to the health risk related to occupational air pollution exposure, we
assessed concentrations and identified sources of particles and volatile organic
compounds (VOCs) in a handcraft workshop producing fishing lures. The work
processes in the site included polyurethane molding, spray painting, lacquering,
and gluing. We measured total VOC (TVOC) concentrations and particle size
distributions at three locations representing the various phases of the
manufacturing and assembly process. The mean working-hour TVOC concentrations in
three locations studied were 41, 37, and 24 ppm according to photo-ionization
detector measurements. The mean working-hour particle number concentration varied
between locations from 3000 to 36,000 cm-3. Analysis of temporal and spatial
variations of TVOC concentrations revealed that there were at least four
substantial VOC sources: spray gluing, mold-release agent spraying, continuous
evaporation from various lacquer and paint containers, and either spray painting
or lacquering (probably both). The mold-release agent spray was indirectly also a
major source of ultrafine particles. The workers' exposure can be reduced by
improving the local exhaust ventilation at the known sources and by increasing
the ventilation rate in the area with the continuous source.
PMID- 25849540
TI - Cross-sectional associations of depressive symptom severity and functioning with
health service use by older people in low-and-middle income countries.
AB - BACKGROUND: Comprehensive understanding of the determinants of health service use
(HSU) by older people with depression is essential for health service planning
for an ageing global population. This study aimed to determine the extent to
which depressive symptom severity and functioning are associated with HSU by
older people with depression in low and middle income countries (LMICs). METHODS:
A cross-sectional analysis of the 10/66 Dementia Research Group population-based
surveys dataset. Participants (n = 4590) were those aged 65 or older, in the
clinical range for depressive symptoms (defined as scoring four or more on the
EURO-D), living in 13 urban and/or rural catchment areas in nine LMICs.
Associations were calculated using Poisson regression and random-effects meta
analysis. RESULTS: After adjustment for confounding variables, (EURO-D)
depressive symptom severity was significantly associated with "any community HSU"
(Pooled Prevalence Ratios = 1.02; 95% CI = 1.01-1.03) but not hospital admission.
Conversely, after adjustment, (WHODAS-II) functioning was significantly
associated with hospital admission (Pooled PR = 1.14; 95% CI = 1.02-1.26) but not
"any community HSU". CONCLUSIONS: Depressive symptom severity does not explain a
large proportion of the variance in HSU by older people with depression in LMICs.
The association of functioning with this HSU is worthy of further investigation.
In LMICs, variables related to accessibility may be more important correlates of
HSU than variables directly related to health problems.
PMID- 25849541
TI - Mouse mammary stem cells express prognostic markers for triple-negative breast
cancer.
AB - INTRODUCTION: Triple-negative breast cancer (TNBC) is a heterogeneous group of
tumours in which chemotherapy, the current mainstay of systemic treatment, is
often initially beneficial but with a high risk of relapse and metastasis. There
is currently no means of predicting which TNBC will relapse. We tested the
hypothesis that the biological properties of normal stem cells are re-activated
in tumour metastasis and that, therefore, the activation of normal mammary stem
cell-associated gene sets in primary TNBC would be highly prognostic for relapse
and metastasis. METHODS: Mammary basal stem and myoepithelial cells were isolated
by flow cytometry and tested in low-dose transplant assays. Gene expression
microarrays were used to establish expression profiles of the stem and
myoepithelial populations; these were compared to each other and to our
previously established mammary epithelial gene expression profiles. Stem cell
genes were classified by Gene Ontology (GO) analysis and the expression of a
subset analysed in the stem cell population at single cell resolution. Activation
of stem cell genes was interrogated across different breast cancer cohorts and
within specific subtypes and tested for clinical prognostic power. RESULTS: A set
of 323 genes was identified that was expressed significantly more highly in the
purified basal stem cells compared to all other cells of the mammary epithelium.
A total of 109 out of 323 genes had been associated with stem cell features in at
least one other study in addition to our own, providing further support for their
involvement in the biology of this cell type. GO analysis demonstrated an
enrichment of these genes for an association with cell migration, cytoskeletal
regulation and tissue morphogenesis, consistent with a role in invasion and
metastasis. Single cell resolution analysis showed that individual cells co
expressed both epithelial- and mesenchymal-associated genes/proteins. Most
strikingly, we demonstrated that strong activity of this stem cell gene set in
TNBCs identified those tumours most likely to rapidly progress to metastasis.
CONCLUSIONS: Our findings support the hypothesis that the biological properties
of normal stem cells are drivers of metastasis and that these properties can be
used to stratify patients with a highly heterogeneous disease such as TNBC.
PMID- 25849542
TI - The short-term cost-effectiveness of once-daily liraglutide versus once-weekly
exenatide for the treatment of type 2 diabetes mellitus in the United States.
AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with
substantial morbidity, mortality, and economic impacts. Glucagon-like peptide-1
(GLP-1) receptor agonists, such as once-daily (QD) liraglutide and once-weekly
(QW) exenatide, are FDA-approved treatment for T2DM. Head-to-head trials and meta
analyses comparing these agents have reported clinically meaningful improvements
but small differences in glycemic control between both agents. In this study, we
calculate and compare the cost-effectiveness implications of these alternative
effectiveness outcomes. METHODS: We developed a decision model to evaluate the
short-term cost-effectiveness of exenatide QW 2 mg versus liraglutide QD 1.8 mg
in T2DM patients, with effectiveness measured as reduction in glycated hemoglobin
(HbA1c). In the base case, the model tracks change in HbA1c and direct medical
expenditure over a 6-month time horizon. We calculated and compared the cost per
1% reduction in HbA1c of models populated with clinical data from a head-to-head
randomized, controlled trial (DURATION-6) and a network meta-analysis.
Expenditure inputs were derived from wholesale acquisition costs and published
sources. RESULTS: In the base case, 6-month expenditure for the liraglutide and
exenatide strategies were $3,509 and $2,618, respectively. Using clinical data
from DURATION-6 and the network meta-analysis, the liraglutide strategy had an
incremental cost per 1% reduction in HbA1c of $4,773 and $27,179, respectively.
The most influential model parameters were drug costs, magnitude of HbA1c
reduction in patients on treatment for >1 month, and liraglutide gastrointestinal
adverse event rate. In probabilistic sensitivity analyses (PSA) using DURATION-6
data, the exenatide strategy was optimal at willingness-to-pay levels below
$4,800 per 1% reduction in HbA1c. In a PSA using meta-analysis data, the
exenatide strategy was dominant. CONCLUSIONS: Our modeled results demonstrate
that the effectiveness and cost-effectiveness of liraglutide QD 1.8 mg relative
to exenatide QW 2 mg depend largely on the chosen source of the clinical data.
PMID- 25849544
TI - GATE validation of standard dual energy corrections in small animal SPECT-CT.
AB - This paper addresses 123I and 125I dual isotope SPECT imaging, which can be
challenging because of spectrum overlap in the low energy spectrums of these
isotopes. We first quantify the contribution of low-energy photons from each
isotope using GATE-based Monte Carlo simulations for the MOBY mouse phantom. We
then describe and analyze a simple, but effective method that uses the ratio of
detected low and high energy 123I activity to separate the mixed low energy 123I
and 125I activities. Performance is compared with correction methods used in
conventional tissue biodistribution techniques. The results indicate that the
spectrum overlap effects can be significantly reduced, if not entirely
eliminated, when attenuation and scatter is either absent or corrected for using
standard methods. In particular, we show that relative activity levels of the two
isotopes can be accurately estimated for a wide range of organs and provide
quantitative validation that standard methods for spectrum overlap correction
provide reasonable estimates for reasonable corrections in small-animal SPECT/CT
imaging.
PMID- 25849543
TI - Leukocyte-derived IFN-alpha/beta and epithelial IFN-lambda constitute a
compartmentalized mucosal defense system that restricts enteric virus infections.
AB - Epithelial cells are a major port of entry for many viruses, but the molecular
networks which protect barrier surfaces against viral infections are incompletely
understood. Viral infections induce simultaneous production of type I (IFN
alpha/beta) and type III (IFN-lambda) interferons. All nucleated cells are
believed to respond to IFN-alpha/beta, whereas IFN-lambda responses are largely
confined to epithelial cells. We observed that intestinal epithelial cells,
unlike hematopoietic cells of this organ, express only very low levels of
functional IFN-alpha/beta receptors. Accordingly, after oral infection of IFN
alpha/beta receptor-deficient mice, human reovirus type 3 specifically infected
cells in the lamina propria but, strikingly, did not productively replicate in
gut epithelial cells. By contrast, reovirus replicated almost exclusively in gut
epithelial cells of IFN-lambda receptor-deficient mice, suggesting that the gut
mucosa is equipped with a compartmentalized IFN system in which epithelial cells
mainly respond to IFN-lambda that they produce after viral infection, whereas
other cells of the gut mostly rely on IFN-alpha/beta for antiviral defense. In
suckling mice with IFN-lambda receptor deficiency, reovirus replicated in the gut
epithelium and additionally infected epithelial cells lining the bile ducts,
indicating that infants may use IFN-lambda for the control of virus infections in
various epithelia-rich tissues. Thus, IFN-lambda should be regarded as an
autonomous virus defense system of the gut mucosa and other epithelial barriers
that may have evolved to avoid unnecessarily frequent triggering of the IFN
alpha/beta system which would induce exacerbated inflammation.
PMID- 25849545
TI - Post-PKS tailoring steps of a disaccharide-containing polyene NPP in
Pseudonocardia autotrophica.
AB - A novel polyene compound NPP identified in a rare actinomycetes, Pseudonocardia
autotrophica KCTC9441, was shown to contain an aglycone identical to nystatin but
to harbor a unique di-sugar moiety, mycosaminyl-(alpha1-4)-N-acetyl-glucosamine,
which led to higher solubility and reduced hemolytic activity. Although the nppDI
was proved to be responsible for the transfer of first polyene sugar, mycosamine
in NPP biosynthesis, the gene responsible for the second sugar extending
glycosyltransferase (GT) as well as NPP post-PKS tailoring mechanism remained
unknown. Here, we identified a NPP-specific second sugar extending GT gene named
nppY, located at the edge of the NPP biosynthetic gene cluster. Targeted nppY
gene deletion and its complementation proved that nppY is indeed responsible for
the transfer of second sugar, N-acetyl-glucosamine in NPP biosynthesis. Site
directed mutagenesis on nppY also revealed several amino acid residues critical
for NppY GT function. Moreover, a combination of deletions and complementations
of two GT genes (nppDI and nppY) and one P450 hydroxylase gene (nppL) involved in
the NPP post-PKS biosynthesis revealed that NPP aglycone is sequentially modified
by the two different GTs encoded by nppDI and nppY, respectively, followed by the
nppL-driven regio-specific hydroxylation at the NPP C10 position. These results
set the stage for the biotechnological application of sugar diversification for
the biosynthesis of novel polyene compounds in actinomycetes.
PMID- 25849546
TI - Detection of convergent genome-wide signals of adaptation to tropical forests in
humans.
AB - Tropical forests are believed to be very harsh environments for human life. It is
unclear whether human beings would have ever subsisted in those environments
without external resources. It is therefore possible that humans have developed
recent biological adaptations in response to specific selective pressures to cope
with this challenge. To understand such biological adaptations we analyzed genome
wide SNP data under a Bayesian statistics framework, looking for outlier markers
with an overly large extent of differentiation between populations living in a
tropical forest, as compared to genetically related populations living outside
the forest in Africa and the Americas. The most significant positive selection
signals were found in genes related to lipid metabolism, the immune system, body
development, and RNA Polymerase III transcription initiation. The results are
discussed in the light of putative tropical forest selective pressures, namely
food scarcity, high prevalence of pathogens, difficulty to move, and inefficient
thermoregulation. Agreement between our results and previous studies on the pygmy
phenotype, a putative prototype of forest adaptation, were found, suggesting that
a few genetic regions previously described as associated with short stature may
be evolving under similar positive selection in Africa and the Americas. In
general, convergent evolution was less pervasive than local adaptation in one
single continent, suggesting that Africans and Amerindians may have followed
different routes to adapt to similar environmental selective pressures.
PMID- 25849547
TI - Clustering consumers based on trust, confidence and giving behaviour: data-driven
model building for charitable involvement in the Australian not-for-profit
sector.
AB - Organisations in the Not-for-Profit and charity sector face increasing
competition to win time, money and efforts from a common donor base.
Consequently, these organisations need to be more proactive than ever. The
increased level of communications between individuals and organisations today,
heightens the need for investigating the drivers of charitable giving and
understanding the various consumer groups, or donor segments, within a
population. It is contended that 'trust' is the cornerstone of the not-for-profit
sector's survival, making it an inevitable topic for research in this context. It
has become imperative for charities and not-for-profit organisations to adopt for
profit's research, marketing and targeting strategies. This study provides the
not-for-profit sector with an easily-interpretable segmentation method based on a
novel unsupervised clustering technique (MST-kNN) followed by a feature saliency
method (the CM1 score). A sample of 1,562 respondents from a survey conducted by
the Australian Charities and Not-for-profits Commission is analysed to reveal
donor segments. Each cluster's most salient features are identified using the CM1
score. Furthermore, symbolic regression modelling is employed to find cluster
specific models to predict 'low' or 'high' involvement in clusters. The MST-kNN
method found seven clusters. Based on their salient features they were labelled
as: the 'non-institutionalist charities supporters', the 'resource allocation
critics', the 'information-seeking financial sceptics', the 'non-questioning
charity supporters', the 'non-trusting sceptics', the 'charity management
believers' and the 'institutionalist charity believers'. Each cluster exhibits
their own characteristics as well as different drivers of 'involvement'. The
method in this study provides the not-for-profit sector with a guideline for
clustering, segmenting, understanding and potentially targeting their donor base
better. If charities and not-for-profit organisations adopt these strategies,
they will be more successful in today's competitive environment.
PMID- 25849548
TI - Deep phylogenetic analysis of haplogroup G1 provides estimates of SNP and STR
mutation rates on the human Y-chromosome and reveals migrations of Iranic
speakers.
AB - Y-chromosomal haplogroup G1 is a minor component of the overall gene pool of
South-West and Central Asia but reaches up to 80% frequency in some populations
scattered within this area. We have genotyped the G1-defining marker M285 in 27
Eurasian populations (n= 5,346), analyzed 367 M285-positive samples using 17 Y
STRs, and sequenced ~11 Mb of the Y-chromosome in 20 of these samples to an
average coverage of 67X. This allowed detailed phylogenetic reconstruction. We
identified five branches, all with high geographical specificity: G1-L1323 in
Kazakhs, the closely related G1-GG1 in Mongols, G1-GG265 in Armenians and its
distant brother clade G1-GG162 in Bashkirs, and G1-GG362 in West Indians. The
haplotype diversity, which decreased from West Iran to Central Asia, allows us to
hypothesize that this rare haplogroup could have been carried by the expansion of
Iranic speakers northwards to the Eurasian steppe and via founder effects became
a predominant genetic component of some populations, including the Argyn tribe of
the Kazakhs. The remarkable agreement between genetic and genealogical trees of
Argyns allowed us to calibrate the molecular clock using a historical date (1405
AD) of the most recent common genealogical ancestor. The mutation rate for Y
chromosomal sequence data obtained was 0.78*10-9 per bp per year, falling within
the range of published rates. The mutation rate for Y-chromosomal STRs was 0.0022
per locus per generation, very close to the so-called genealogical rate. The
"clan-based" approach to estimating the mutation rate provides a third, middle
way between direct farther-to-son comparisons and using archeologically known
migrations, whose dates are subject to revision and of uncertain relationship to
genetic events.
PMID- 25849549
TI - A novel biosurfactant produced by Aureobasidium pullulans L3-GPY from a tiger
lily wild flower, Lilium lancifolium Thunb.
AB - Yeast biosurfactants are important biotechnological products in the food
industry, and they have medical and cosmeceutical applications owing to their
specific modes of action, low toxicity, and applicability. Thus, we have isolated
and examined biosurfactant-producing yeast for various industrial and medical
applications. A rapid and simple method was developed to screen biosurfactant
producing yeasts for high production of eco-friendly biosurfactants. Using this
method, several potential niches of biosurfactant-producing yeasts, such as wild
flowers, were investigated. We successfully selected a yeast strain, L3-GPY, with
potent surfactant activity from a tiger lily, Lilium lancifolium Thunb. Here, we
report the first identification of strain L3-GPY as the black yeast Aureobasidium
pullulans. In addition, we isolated a new low-surface-tension chemical,
designated glycerol-liamocin, from the culture supernatant of strain L3-GPY
through consecutive chromatography steps, involving an ODS column, solvent
partition, silica gel, Sephadex LH-20, and an ODS Sep-Pak cartridge column. The
chemical structure of glycerol-liamocin, determined by mass spectrometry and
nuclear magnetic resonance spectroscopy, indicates that it is a novel compound
with the molecular formula C33H62O12. Furthermore, glycerol-liamocin exhibited
potent biosurfactant activity (31 mN/m). These results suggest that glycerol
liamocin is a potential novel biosurfactantfor use in various industrial
applications.
PMID- 25849551
TI - Corrigendum.
PMID- 25849550
TI - G-CSF protects human brain vascular endothelial cells injury induced by high
glucose, free fatty acids and hypoxia through MAPK and Akt signaling.
AB - Granulocyte-colony stimulating factor (G-CSF) has been shown to play a
neuroprotective role in ischemic stroke by mobilizing bone marrow (BM)-derived
endothelial progenitor cells (EPCs), promoting angiogenesis, and inhibiting
apoptosis. Impairments in mobilization and function of the BM-derived EPCs have
previously been reported in animal and human studies of diabetes where there is
both reduction in the levels of the BM-derived EPCs and its ability to promote
angiogenesis. This is hypothesized to account for the pathogenesis of diabetic
vascular complications such as stroke. Here, we sought to investigate the effects
of G-CSF on diabetes-associated cerebral vascular defect. We observed that
pretreatment of the cultured human brain vascular endothelial cells (HBVECs) with
G-CSF largely prevented cell death induced by the combination stimulus with high
glucose, free fatty acids (FFA) and hypoxia by increasing cell viability,
decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by
transmission electron microscope (TEM) revealed that G-CSF treatment nicely
reduced combination stimulus-induced cell apoptosis. The results from fluorescent
probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular
calcium ions under combination stimulus. We also found that G-CSF enhanced the
expression of cell cycle proteins such as human cell division cycle protein 14A
(hCdc14A), cyclinB and cyclinE, inhibited p53 activity, and facilitated cell
cycle progression following combination stimulus. In addition, activation of
extracellular signal-regulated kinase1/2 (ERK1/2) and Akt, and deactivation of c
Jun N terminal kinase (JNK) and p38 were proved to be required for the pro
survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G
CSF is capable of alleviating HBVECs injury triggered by the combination
administration with high glucose, FFA and hypoxia involving the mitogen-activated
protein kinases (MAPK) and Akt signaling cascades. G-CSF may represent a
promising therapeutic agent for diabetic stroke.
PMID- 25849552
TI - The evaluation of the risk factors for non-muscle invasive bladder cancer (NMIBC)
recurrence after transurethral resection (TURBt) in Chinese population.
AB - OBJECTIVE: The risk factors of bladder cancer recurrence after transurethral
resection of bladder tumor (TURBt) were poorly understood, especially in Chinese
population. This study evaluated the potential risk factors of recurrence based
on a Chinese population. MATERIALS AND METHODS: A total of 698 patients that
received TURBt procedure in our institute from 2000 to 2012 were recruited in
this study. Clinical information was collected. The patients were followed up
according to the schedule recommended by Chinese guideline. RESULTS: A total of
583 males (83.5%) and 115 females (16.5%) were enrolled in our study. The median
follow-up duration was 51.5 months. Gender, chief complain, tumor size, number of
lesions, histological grade and chemotherapeutic agents were found significantly
associated with patients' short-term recurrence (less than 1 year) (All p<0.05).
In the multivariate analysis, tumor size, number of lesions, histological grade
and chemotherapeutic agents were significantly related to patients' short-term
recurrence (less than 1 year) (All p<0.05). A multivariate model based on tumor
size, number of lesions, histological grade and chemotherapeutic agents had an
AUC of 0.697, which significantly improved the prediction utility for bladder
cancer short-term recurrence (less than 1 year) than any single factor In the
multivariate Cox regression, tumor size greater than 3 cm, multifocal lesions,
worsen histological grade and non-urothelial carcinoma was related to time to
recurrence (TR). CONCLUSION: Patients with larger tumor size, multifocal number
of lesions, higher tumor grade and who received chemotherapeutic agents other
than Epirubicin and Pirarubicin might have higher risks of recurrence less than 1
year. Tumor size, number of lesions, pathology and histological grade might be
associated with TR. As Bacille Calmette-Guerin (BCG) is currently not approved
for bladder cancer in China, Epirubicin and Pirarubicin might be considered prior
to other chemotherapy medications when providing post-operative instillation of
chemotherapy.
PMID- 25849553
TI - Metrics for assessing cytoskeletal orientational correlations and consistency.
AB - In biology, organization at multiple scales potentiates biological function.
Current advances in staining and imaging of biological tissues provide a wealth
of data, but there are few metrics to quantitatively describe these findings. In
particular there is a need for a metric that would characterize the correlation
and consistency of orientation of different biological constructs within a
tissue. We aimed to create such a metric and to demonstrate its use with images
of cardiac tissues. The co-orientational order parameter (COOP) was based on the
mathematical framework of a classical parameter, the orientational order
parameter (OOP). Theorems were proven to illustrate the properties and boundaries
of the COOP, which was then applied to both synthetic and experimental data. We
showed the COOP to be useful for quantifying the correlation of orientation of
constructs such as actin filaments and sarcomeric Z-lines. As expected, cardiac
tissues showed perfect correlation between actin filaments and Z-lines. We also
demonstrated the use of COOP to quantify the consistency of construct orientation
within cells of the same shape. The COOP provides a quantitative tool to
characterize tissues beyond co-localization or single construct orientation
distribution. In the future, this new parameter could be used to represent the
quantitative changes during maturation of cardiac tissue, pathological
malformation, and other processes.
PMID- 25849554
TI - New point mutations in surface and core genes of hepatitis B virus associated
with acute on chronic liver failure identified by complete genomic sequencing.
AB - The objective of this study was to identify new viral biomarkers associated with
acute on chronic liver failure (ACLF) by complete genomic sequencing of HBV.
Hepatitis B virus mutations associated with ACLF were screened by Illumina high
throughput sequencing in twelve ACLF cases and twelve age-matched mild chronic
hepatitis B patients, which were validated in 438 chronic hepatitis B patients
(80 asymptomatic carriers, 152 mild chronic hepatitis B patients, 102 severe
chronic hepatitis B patients and 104 ACLF patients) by direct sequencing. The
results of Illumina sequencing showed that the mutations at 7 sites (T216C,
G285A, A1846T, G1896A, C1913A/G, A2159G, and A2189C) of 12 ACLF patients were
significantly higher than those of 12 controls. In the validation cohorts, a
significantly higher ratio of genotype B to C was found in patients with ACLF
than in patients with non-ACLF. Multivariate analysis showed that T216C, G1896A,
C1913A/G and A2159G/C were independent risk factors for ACLF. C216 in any
combination, A/G1913 in any combination, and G/C2159 in any combination had high
specificity for ACLF. In summary, T216C and A2159G/C mutations were novel factors
independently associated with ACLF. Combined mutations in hepatitis B cases could
play important roles in ACLF development.
PMID- 25849555
TI - Helping reasoners succeed in the Wason selection task: when executive learning
discourages heuristic response but does not necessarily encourage logic.
AB - Reasoners make systematic logical errors by giving heuristic responses that
reflect deviations from the logical norm. Influential studies have suggested
first that our reasoning is often biased because we minimize cognitive effort to
surpass a cognitive conflict between heuristic response from system 1 and
analytic response from system 2 thinking. Additionally, cognitive control
processes might be necessary to inhibit system 1 responses to activate a system 2
response. Previous studies have shown a significant effect of executive learning
(EL) on adults who have transferred knowledge acquired on the Wason selection
task (WST) to another isomorphic task, the rule falsification task (RFT). The
original paradigm consisted of teaching participants to inhibit a classical
matching heuristic that sufficed the first problem and led to significant EL
transfer on the second problem. Interestingly, the reasoning tasks differed in
inhibiting-heuristic metacognitive cost. Success on the WST requires half
suppression of the matching elements. In contrast, the RFT necessitates a global
rejection of the matching elements for a correct answer. Therefore, metacognitive
learning difficulty most likely differs depending on whether one uses the first
or second task during the learning phase. We aimed to investigate this difficulty
and various matching-bias inhibition effects in a new (reversed) paradigm. In
this case, the transfer effect from the RFT to the WST could be more difficult
because the reasoner learns to reject all matching elements in the first task. We
observed that the EL leads to a significant reduction in matching selections on
the WST without increasing logical performances. Interestingly, the acquired
metacognitive knowledge was too "strictly" transferred and discouraged matching
rather than encouraging logic. This finding underlines the complexity of learning
transfer and adds new evidence to the pedagogy of reasoning.
PMID- 25849556
TI - Degradation and mineralization of phenol compounds with goethite catalyst and
mineralization prediction using artificial intelligence.
AB - The efficiency of phenol degradation via Fenton reaction using mixture of
heterogeneous goethite catalyst with homogeneous ferrous ion was analyzed as a
function of three independent variables, initial concentration of phenol (60 to
100 mg /L), weight ratio of initial concentration of phenol to that of H2O2 (1: 6
to 1: 14) and, weight ratio of initial concentration of goethite catalyst to that
of H2O2 (1: 0.3 to 1: 0.7). More than 90 % of phenol removal and more than 40% of
TOC removal were achieved within 60 minutes of reaction. Two separate models were
developed using artificial neural networks to predict degradation percentage by a
combination of Fe3+ and Fe2+ catalyst. Five operational parameters were employed
as inputs while phenol degradation and TOC removal were considered as outputs of
the developed models. Satisfactory agreement was observed between testing data
and the predicted values (R2Phenol = 0.9214 and R2TOC= 0.9082).
PMID- 25849557
TI - The complete chloroplast and mitochondrial genomes of the green macroalga Ulva
sp. UNA00071828 (Ulvophyceae, Chlorophyta).
AB - Sequencing mitochondrial and chloroplast genomes has become an integral part in
understanding the genomic machinery and the phylogenetic histories of green
algae. Previously, only three chloroplast genomes (Oltmannsiellopsis viridis,
Pseudendoclonium akinetum, and Bryopsis hypnoides) and two mitochondrial genomes
(O. viridis and P. akinetum) from the class Ulvophyceae have been published.
Here, we present the first chloroplast and mitochondrial genomes from the
ecologically and economically important marine, green algal genus Ulva. The
chloroplast genome of Ulva sp. was 99,983 bp in a circular-mapping molecule that
lacked inverted repeats, and thus far, was the smallest ulvophycean plastid
genome. This cpDNA was a highly compact, AT-rich genome that contained a total of
102 identified genes (71 protein-coding genes, 28 tRNA genes, and three ribosomal
RNA genes). Additionally, five introns were annotated in four genes: atpA (1),
petB (1), psbB (2), and rrl (1). The circular-mapping mitochondrial genome of
Ulva sp. was 73,493 bp and follows the expanded pattern also seen in other
ulvophyceans and trebouxiophyceans. The Ulva sp. mtDNA contained 29 protein
coding genes, 25 tRNA genes, and two rRNA genes for a total of 56 identifiable
genes. Ten introns were annotated in this mtDNA: cox1 (4), atp1 (1), nad3 (1),
nad5 (1), and rrs (3). Double-cut-and-join (DCJ) values showed that organellar
genomes across Chlorophyta are highly rearranged, in contrast to the highly
conserved organellar genomes of the red algae (Rhodophyta). A phylogenomic
investigation of 51 plastid protein-coding genes showed that Ulvophyceae is not
monophyletic, and also placed Oltmannsiellopsis (Oltmannsiellopsidales) and
Tetraselmis (Chlorodendrophyceae) closely to Ulva (Ulvales) and Pseudendoclonium
(Ulothrichales).
PMID- 25849558
TI - Tuberculosis prevention in South Africa.
AB - BACKGROUND: South Africa has one of the highest per capita rates of tuberculosis
(TB) incidence in the world. In 2012, the South African government produced a
National Strategic Plan (NSP) to control the spread of TB with the ambitious aim
of zero new TB infections and deaths by 2032, and a halving of the 2012 rates by
2016. METHODS: We used a transmission model to investigate whether the NSP
targets could be reached if immediate scale up of control methods had happened in
2014. We explored the potential impact of four intervention portfolios; 1) "NSP"
represents the NSP strategy, 2) "WHO" investigates increasing antiretroviral
therapy eligibility, 3) "Novel Strategies" considers new isoniazid preventive
therapy strategies and HIV "Universal Test and Treat" and 4) "Optimised" contains
the most effective interventions. FINDINGS: We find that even with this scale-up,
the NSP targets are unlikely to be achieved. The portfolio that achieved the
greatest impact was "Optimised", followed closely by "NSP". The "WHO" and "Novel
Strategies" had little impact on TB incidence by 2050. Of the individual
interventions explored, the most effective were active case finding and
reductions in pre-treatment loss to follow up which would have a large impact on
TB burden. CONCLUSION: Use of existing control strategies has the potential to
have a large impact on TB disease burden in South Africa. However, our results
suggest that the South African TB targets are unlikely to be reached without new
technologies. Despite this, TB incidence could be dramatically reduced by finding
and starting more TB cases on treatment.
PMID- 25849561
TI - Direct and two-step bioorthogonal probes for Bruton's tyrosine kinase based on
ibrutinib: a comparative study.
AB - Ibrutinib is a covalent and irreversible inhibitor of Bruton's tyrosine kinase
(BTK) and has been approved for the treatment of haematological malignancies,
such as chronic lymphocytic leukaemia, mantle cell lymphoma and Waldenstrom's
macroglobulinemia. The covalent and irreversible nature of its molecular mode of
action allows identification and monitoring of its target in an activity-based
protein profiling (ABPP) setting. Fluorescent and biotinylated ibrutinib
derivatives have appeared in the literature in recent years to monitor BTK in
vitro and in situ. The work described here complements this existing methodology
and pertains a comparative study on the efficacy of direct and two-step
bioorthogonal ABPP of BTK.
PMID- 25849560
TI - Evaluation of the medicinal herb Graptopetalum paraguayense as a treatment for
liver cancer.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy
and the third most common cause of cancer-related death worldwide. Sorafenib is
the only drug for patients with advanced-stage hepatocellular carcinoma (HCC)
that has been shown to confer a survival benefit to patients with HCC; however,
it has many side effects. Thus, alternate therapeutic strategies with improved
safety and therapeutic efficacy for the management of HCC should be developed.
METHODS AND FINDINGS: We demonstrate that an extract of Graptopetalum
paraguayense (GP) down-regulated the expression levels of several onco-proteins,
including AURKA, AURKB, and FLJ10540, in HCC cells. To isolate the active
components in the GP extracts, we prepared extracts fractions and assessed their
effects on the expression of onco-proteins in HCC cells. The fraction designated
HH-F3 was enriched in active ingredients, exhibited cytotoxic effects, and
suppressed the expression of the onco-proteins in HCC cells. The structure of the
main active compound in HH-F3 was found to be similar to that of the
proanthocyanidin compounds derived from Rhodiola rosea. In addition, a distinct
new compound rich in 3, 4, 5-trihydroxy benzylic moieties was identified in the
HH-F3 preparations. Mechanistic studies indicated that HH-F3 induced apoptosis in
HCC cells by promoting the loss of mitochondrial membrane potential and the
production of reactive oxygen species. HH-F3 also enhanced PTEN expression and
decreased AKT phosphorylation at Ser473 in a concentration-dependent manner in
HCC cells. Moreover combination of GP or HH-F3 and sorafenib synergistically
inhibits the proliferation of Huh7 cells. The treatment of a rat model with
diethylnitrosamine (DEN)-induced liver cancer with extracts of GP and HH-F3
decreased hepatic collagen contents and inhibited tumor growth. CONCLUSIONS:
These results indicate that GP extracts and HH-F3 can protect the liver by
suppressing tumor growth; consequently, these compounds could be considered for
the treatment of HCC.
PMID- 25849559
TI - Patient-derived xenograft models of breast cancer and their predictive power.
AB - Despite advances in the treatment of patients with early and metastatic breast
cancer, mortality remains high due to intrinsic or acquired resistance to
therapy. Increased understanding of the genomic landscape through massively
parallel sequencing has revealed somatic mutations common to specific subtypes of
breast cancer, provided new prognostic and predictive markers, and highlighted
potential therapeutic targets. Evaluating new targets using established cell
lines is limited by the inexact correlation between responsiveness observed in
cell lines versus that elicited in the patient. Patient-derived xenografts (PDXs)
generated from fresh tumor specimens recapitulate the diversity of breast cancer
and reflect histopathology, tumor behavior, and the metastatic properties of the
original tumor. The high degree of genomic preservation evident across primary
tumors and their matching PDXs over serial passaging validate them as important
preclinical tools. Indeed, there is accumulating evidence that PDXs can
recapitulate treatment responses of the parental tumor. The finding that tumor
engraftment is an independent and poor prognostic indicator of patient outcome
represents the first step towards personalized medicine. Here we review the
utility of breast cancer PDX models to study the clonal evolution of tumors and
to evaluate novel therapies and drug resistance.
PMID- 25849562
TI - Nucleosides present on phlebotomine saliva induce immunossuppression and promote
the infection establishment.
AB - BACKGROUND: Sand fly saliva plays a crucial role in establishing Leishmania
infection. We identified adenosine (ADO) and adenosine monophosphate (AMP) as
active pharmacologic compounds present in Phlebotomus papatasi saliva that
inhibit dendritic cell (DC) functions through a PGE2/IL 10-dependent mechanism.
METHODOLOGY/PRINCIPAL FINDINGS: Herein, we prepared a mixture of ADO and AMP in
equimolar amounts similar to those present in the salivary-gland extract (SGE)
form one pair of salivary glands of P. papatasi and co-injected it with
Leishmania amazonensis or L. major into mouse ears. ADO+AMP mimicked exacerbative
effects of P. papatasi saliva in leishmaniasis, increasing parasite burden and
cutaneous lesions. Enzymatic catabolism of salivary nucleosides reversed the SGE
induced immunosuppressive effect associated with IL-10 enhancement.
Immunosuppressive factors COX2 and IL-10 were upregulated and failed to enhance
ear lesion and parasite burden in IL 10-/- infected mice. Furthermore,
nucleosides increased regulatory T cell (Treg) marker expression on CD4+CD25-
cells, suggesting induction of Tregs on effector T cells (T eff). Treg induction
(iTreg) was associated with nucleoside-induced tolerogenic dendritic cells (tDCs)
expressing higher levels of COX2 and IL-10. In vitro generation of Tregs was more
efficient in DCs treated with nucleosides. Suppressive effects of nucleosides
during cutaneous leishmaniasis were mediated through an A2AR-dependent mechanism.
Using BALB/c mice deficient in A2A ADO receptor (A2AR-/-), we showed that co
inoculated mice controlled infection, displaying lower parasite numbers at
infection sites and reduced iTreg generation. CONCLUSION/SIGNIFICANCE: We have
demonstrated that ADO and AMP in P. papatasi saliva mediate exacerbative effects
of Leishmania infection by acting preferentially on DCs promoting a tolerogenic
profile in DCs and by generating iTregs in inflammatory foci through an A2AR
mechanism.
PMID- 25849563
TI - CHADS2 and CHA2DS2-VASc scoring systems for predicting atrial fibrillation
following cardiac valve surgery.
AB - OBJECTIVE: Clinical use of CHADS2 and CHA2DS2-VASc scoring systems for predicting
AF following cardiac surgery have been reported in previous studies and
demonstrated well-validated predictive value. We sought to investigate whether
the two scoring systems are effective for predicting new-onset of AF following
cardiac valve surgery and to demonstrate its potential utility of clinical
assessment. METHODS: Medical records of all patients underwent cardiac valve
surgeries during the period of January 2003 and December 2013 without
preoperative AF at the cardiac center of our university were reviewed. The main
outcome end point of our study was the early new-onset of AF following cardiac
valve surgery. RESULTS: There were overall 518 patients involved in this study,
with 234 (45.17%) developed POAF following valve surgery. Patients with POAF had
older age (P=0.23) and higher BMI (P=0.013) than those without POAF. History of
heart failure (P=0.025), hypertension (P=0.021), previous stroke or TIA
(P=0.032), coronary artery disease (P=0.001), carotid artery disease (P=0.024)
and preoperative medication of statins (P=0.021) were significantly more recorded
in POAF group. Patients with POAF also had higher LAD (P=0.013) and E/e' ratio
(P<0.001). The CHADS2 and CHA2DS2-VASc scores were significantly higher in
patients with POAF (P=0.002; P<0.001), and under univariate and multivariate
regression analysis the CHADS2 and CHA2DS2-VASc scores were significant
predictors of POAF (P=0.001; P<0.001). Based on stratification of CHADS2 and
CHA2DS2-VASc scores, the Kaplan-Meier analysis obtained a higher POAF rate on
patients with higher stratification of CHADS2 and CHA2DS2-VASc scores (P<0.001;
P<0.001). CONCLUSION: In conclusion, CHADS2 and CHA2DS2-VASc scores were directly
associated with the incidence of POAF following valve surgery and a higher score
was strongly predictive of POAF.
PMID- 25849564
TI - Comprehensive identification of arginine methylation in primary T cells reveals
regulatory roles in cell signalling.
AB - The impact of protein arginine methylation on the regulation of immune functions
is virtually unknown. Here, we apply a novel method-isomethionine methyl-SILAC
coupled with antibody-mediated arginine-methylated peptide enrichment to identify
methylated peptides in human T cells by mass spectrometry. This approach allowed
the identification of 2,502 arginine methylation sites from 1,257 tissue-specific
and housekeeping proteins. We find that components of T cell antigen receptor
signal machinery and several key transcription factors that regulate T cell fate
determination are methylated on arginine. Moreover, we demonstrate changes in
arginine methylation stoichiometry during cellular stimulation in a subset of
proteins critical to T cell differentiation. Our data suggest that protein
arginine methyltransferases exert key regulatory roles in T cell activation and
differentiation, opening a new field of investigation in T cell biology.
PMID- 25849565
TI - Use of learning media by undergraduate medical students in pharmacology: a
prospective cohort study.
AB - The ubiquity of the internet and computer-based technologies has an increasing
impact on higher education and the way students access information for learning.
Moreover, there is a paucity of information about the quantitative and
qualitative use of learning media by the current student generation. In this
study we systematically analyzed the use of digital and non-digital learning
resources by undergraduate medical students. Daily online surveys and semi
structured interviews were conducted with a cohort of 338 third year medical
students enrolled in a general pharmacology course. Our data demonstrate a
predominant use of digital over non-digital learning resources (69 +/- 7% vs. 31
+/- 7%; p < 0.01) by students. Most used media for learning were lecture slides
(26.8 +/- 3.0%), apps (22.0 +/- 3.7%) and personal notes (15.5 +/- 2.7%),
followed by textbooks (> 300 pages) (10.6 +/- 3.3%), internet search (7.9 +/-
1.6%) and e-learning cases (7.6 +/- 3.0%). When comparing learning media use of
teaching vs. pre-exam self-study periods, textbooks were used significantly less
during self-study (-55%; p < 0.01), while exam questions (+334%; p < 0.01) and e
learning cases (+176%; p < 0.01) were utilized more. Taken together, our study
revealed a high prevalence and acceptance of digital learning resources by
undergraduate medical students, in particular mobile applications.
PMID- 25849566
TI - Global epidemiology of type 1 diabetes in young adults and adults: a systematic
review.
AB - BACKGROUND: Although type 1 diabetes (T1D) can affect patients of all ages, most
epidemiological studies of T1D focus on disease forms with clinical diagnosis
during childhood and adolescence. Clinically, adult T1D is difficult to
discriminate from certain forms of Type 2 Diabetes (T2D) and from Latent
Autoimmune Diabetes in Adults (LADA). METHODS: A systematic review of the
literature was performed to retrieve original papers in English, French and
Spanish published up to November 6, 2014, reporting the incidence of T1D among
individuals aged over 15 years. The study was carried out according to the PRISMA
recommendations. RESULTS: We retrieved information reporting incidence of T1D
among individuals aged more than 15 years in 35 countries, and published in 70
articles between 1982 and 2014. Specific anti-beta-cell proteins or C-peptide
detection were performed in 14 of 70 articles (20%). The most frequent diagnostic
criteria used were clinical symptoms and immediate insulin therapy. Country-to
country variations of incidence in those aged >15 years paralleled those of
children in all age groups. T1D incidence was larger in males than in females in
44 of the 54 (81%) studies reporting incidence by sex in people >15 years of age.
The overall mean male-to-female ratio in the review was 1.47 (95% CI = 1.33-1.60,
SD = 0.49, n = 54, p = <0.0001). Overall, T1D incidence decreased in adulthood,
after the age of 14 years. CONCLUSIONS: Few studies on epidemiology of T1D in
adults are available worldwide, as compared to those reporting on children with
T1D. The geographical variations of T1D incidence in adults parallel those
reported in children. As opposed to what is known in children, the incidence is
generally larger in males than in females. There is an unmet need to evaluate the
incidence of autoimmune T1D in adults, using specific autoantibody detection, and
to better analyze epidemiological specificities - if any - of adult T1D. PROSPERO
REGISTRATION NUMBER: CRD42012002369.
PMID- 25849567
TI - Spatial analysis of Schistosomiasis in Hubei Province, China: a GIS-based
analysis of Schistosomiasis from 2009 to 2013.
AB - BACKGROUND: Schistosomiasis remains a major public health problem in China. The
major endemic areas are located in the lake and marshland regions of southern
China, particularly in areas along the middle and low reach of the Yangtze River.
Spatial analytical techniques are often used in epidemiology to identify spatial
clusters in disease regions. This study assesses the spatial distribution of
schistosomiasis and explores high-risk regions in Hubei Province, China to
provide guidance on schistosomiasis control in marshland regions. METHODS: In
this study, spatial autocorrelation methodologies, including global Moran's I and
local Getis-Ord statistics, were utilized to describe and map spatial clusters
and areas where human Schistosoma japonicum infection is prevalent at the county
level in Hubei province. In addition, linear logistic regression model was used
to determine the characteristics of spatial autocorrelation with time. RESULTS:
The infection rates of S. japonicum decreased from 2009 to 2013. The global
autocorrelation analysis results on the infection rate of S. japonicum for five
years showed statistical significance (Moran's I > 0, P < 0.01), which suggested
that spatial clusters were present in the distribution of S. japonicum infection
from 2009 to 2013. Local autocorrelation analysis results showed that the number
of highly aggregated areas ranged from eight to eleven within the five-year
analysis period. The highly aggregated areas were mainly distributed in eight
counties. CONCLUSIONS: The spatial distribution of human S. japonicum infections
did not exhibit a temporal change at the county level in Hubei Province. The risk
factors that influence human S. japonicum transmission may not have changed after
achieving the national criterion of infection control. The findings indicated
that spatial-temporal surveillance of S. japonicum transmission plays a
significant role on schistosomiasis control. Timely and integrated prevention
should be continued, especially in the Yangtze River Basin of Jianghan Plain
area.
PMID- 25849568
TI - What are priorities for deprescribing for elderly patients? Capturing the voice
of practitioners: a modified delphi process.
AB - Polypharmacy and inappropriate medication use among older adults contribute to
adverse drug reactions, falls, cognitive impairment, noncompliance,
hospitalization and mortality. While deprescribing - tapering, reducing or
stopping a medication - is feasible and relatively safe, clinicians find it
difficult to carry out. Deprescribing guidelines would facilitate this process.
The aim of this paper is to identify and prioritize medication classes where
evidence-based deprescribing guidelines would be of benefit to clinicians. A
modified Delphi approach included a literature review to identify potentially
inappropriate medications for the elderly, an expert panel to develop survey
content and three survey rounds to seek consensus on priorities. Panel
participants included three pharmacists, two family physicians and one social
scientist. Sixty-five Canadian geriatrics experts (36 pharmacists, 19 physicians
and 10 nurse practitioners) participated in the survey. Twenty-nine drugs/drug
classes were included in the first survey with 14 reaching the required (>= 70%)
level of consensus, and 2 new drug classes added from qualitative comments. Fifty
three participants completed round two, and 47 participants completed round
three. The final five priorities were benzodiazepines, atypical antipsychotics,
statins, tricyclic antidepressants, and proton pump inhibitors; nine other drug
classes were also identified as being in need of evidence-based deprescribing
guidelines. The Delphi consensus process identified five priority drug classes
for which expert clinicians felt guidance is needed for deprescribing. The
classes of drugs that emerged strongly from the rankings dealt with mental
health, cardiovascular, gastroenterological, and neurological conditions. The
results suggest that deprescribing and overtreatment occurs through the full
spectrum of primary care, and that evidence-based deprescribing guidelines are a
priority in the care of the elderly.
PMID- 25849570
TI - Correction: pollution breaks down the genetic architecture of life history traits
in Caenorhabditis elegans.
PMID- 25849569
TI - Interactive and independent associations between the socioeconomic and objective
built environment on the neighbourhood level and individual health: a systematic
review of multilevel studies.
AB - BACKGROUND: The research question how contextual factors of neighbourhood
environments influence individual health has gained increasing attention in
public health research. Both socioeconomic neighbourhood characteristics and
factors of the built environment play an important role for health and health
related behaviours. However, their reciprocal relationships have not been
systematically reviewed so far. This systematic review aims to identify studies
applying a multilevel modelling approach which consider both neighbourhood
socioeconomic position (SEP) and factors of the objective built environment
simultaneously in order to disentangle their independent and interactive effects
on individual health. METHODS: The three databases PubMed, PsycINFO, and Web of
Science were systematically searched with terms for title and abstract screening.
Grey literature was not included. Observational studies from USA, Canada,
Australia, New Zealand, and Western European countries were considered which
analysed simultaneously factors of neighbourhood SEP and the objective built
environment with a multilevel modelling approach. Adjustment for individual SEP
was a further inclusion criterion. RESULTS: Thirty-three studies were included in
qualitative synthesis. Twenty-two studies showed an independent association
between characteristics of neighbourhood SEP or the built environment and
individual health outcomes or health-related behaviours. Twenty-one studies found
cross-level or within-level interactions either between neighbourhood SEP and the
built environment, or between neighbourhood SEP or the built environment and
individual characteristics, such as sex, individual SEP or ethnicity. Due to the
large variation of study design and heterogeneous reporting of results the
identification of consistent findings was problematic and made quantitative
analysis not possible. CONCLUSIONS: There is a need for studies considering
multiple neighbourhood dimensions and applying multilevel modelling in order to
clarify their causal relationship towards individual health. Especially, more
studies using comparable characteristics of neighbourhood SEP and the objective
built environment and analysing interactive effects are necessary to disentangle
health impacts and identify vulnerable neighbourhoods and population groups.
PMID- 25849571
TI - Dynamic changes in amino acid concentration profiles in patients with sepsis.
AB - OBJECTIVES: The goal of this work was to explore the dynamic concentration
profiles of 42 amino acids and the significance of these profiles in relation to
sepsis, with the aim of providing guidance for clinical therapies. METHODS:
Thirty-five critically ill patients with sepsis were included. These patients
were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups
or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the
patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care
unit (ICU) admission, and the serum concentrations of 42 amino acids were
measured. RESULTS: The metabolic spectrum of the amino acids changed dramatically
in patients with sepsis. As the disease progressed further or with poor
prognosis, the levels of the different amino acids gradually increased,
decreased, or fluctuated over time. The concentrations of sulfur-containing amino
acids (SAAs), especially taurine, decreased significantly as the severity of
sepsis worsened or with poor prognosis of the patient. The serum concentrations
of SAAs, especially taurine, exhibited weak negative correlations with the
Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and
Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the
receiver operating characteristic curves of cystine, taurine, and SAA levels and
the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623,
0.674, 0.678, 0.86, and 0.857, respectively. CONCLUSIONS: Critically ill patients
with disorders of amino acid metabolism, especially of SAAs such as cystine and
taurine, may provide an indicator of the need for the nutritional support of
sepsis in the clinic. TRIAL REGISTRATION: ClinicalTrial.gov identifier
NCT01818830.
PMID- 25849572
TI - Childhood trauma and personal mastery: their influence on emotional reactivity to
everyday events in a community sample of middle-aged adults.
AB - Childhood trauma is associated with premature declines in health in midlife and
old age. Pathways that have been implicated, but less studied include social
emotional regulation, biological programming, and habitual patterns of thought
and action. In this study we focused on childhood trauma's influence via
alterations in social-emotional regulation to everyday life events, a pathway
that has been linked to subsequent health effects. Data from a 30-day daily diary
of community residents who participated in a study of resilience in Midlife (n =
191, Mage = 54, SD = 7.50, 54% women) was used to examine whether self-reports of
childhood trauma were associated with daily well-being, as well as reported and
emotional reactivity to daily negative and positive events. Childhood trauma
reports were associated with reporting lower overall levels of and greater
variability in daily well-being. Childhood trauma was linked to greater reports
of daily negative events, but not to positive events. Focusing on emotional
reactivity to daily events, residents who reported higher levels of childhood
trauma showed stronger decreases in well-being when experiencing negative events
and also stronger increases in well-being with positive events. For those
reporting childhood trauma, higher levels of mastery were associated with
stronger decreases in well-being with negative events and stronger increases in
well-being with positive events, suggesting that mastery increases sensitivity to
daily negative and positive events. Our results suggest that childhood trauma may
lead to poorer health in midlife through disturbances in the patterns of everyday
life events and responses to those events. Further, our findings indicate that
mastery may have a different meaning for those who experienced childhood trauma.
We discuss social-emotional regulation as one pathway linking childhood trauma to
health, and psychosocial resources to consider when building resilience-promoting
interventions for mitigating the detrimental health effects of childhood trauma.
PMID- 25849573
TI - Integration of transcriptome and whole genomic resequencing data to identify key
genes affecting swine fat deposition.
AB - Fat deposition is highly correlated with the growth, meat quality, reproductive
performance and immunity of pigs. Fatty acid synthesis takes place mainly in the
adipose tissue of pigs; therefore, in this study, a high-throughput massively
parallel sequencing approach was used to generate adipose tissue transcriptomes
from two groups of Songliao black pigs that had opposite backfat thickness
phenotypes. The total number of paired-end reads produced for each sample was in
the range of 39.29-49.36 millions. Approximately 188 genes were differentially
expressed in adipose tissue and were enriched for metabolic processes, such as
fatty acid biosynthesis, lipid synthesis, metabolism of fatty acids, etinol,
caffeine and arachidonic acid and immunity. Additionally, many genetic variations
were detected between the two groups through pooled whole-genome resequencing.
Integration of transcriptome and whole-genome resequencing data revealed
important genomic variations among the differentially expressed genes for fat
deposition, for example, the lipogenic genes. Further studies are required to
investigate the roles of candidate genes in fat deposition to improve pig
breeding programs.
PMID- 25849574
TI - The extracytoplasmic linker peptide of the sensor protein SaeS tunes the kinase
activity required for staphylococcal virulence in response to host signals.
AB - Bacterial pathogens often employ two-component systems (TCSs), typically
consisting of a sensor kinase and a response regulator, to control expression of
a set of virulence genes in response to changing host environments. In
Staphylococcus aureus, the SaeRS TCS is essential for in vivo survival of the
bacterium. The intramembrane-sensing histidine kinase SaeS contains, along with a
C-terminal kinase domain, a simple N-terminal domain composed of two
transmembrane helices and a nine amino acid-long extracytoplasmic linker peptide.
As a molecular switch, SaeS maintains low but significant basal kinase activity
and increases its kinase activity in response to inducing signals such as human
neutrophil peptide 1 (HNP1). Here we show that the linker peptide of SaeS
controls SaeS's basal kinase activity and that the amino acid sequence of the
linker peptide is highly optimized for its function. Without the linker peptide,
SaeS displays aberrantly elevated kinase activity even in the absence of the
inducing signal, and does not respond to HNP1. Moreover, SaeS variants with
alanine substitution of the linker peptide amino acids exhibit altered basal
kinase activity and/or irresponsiveness to HNP1. Biochemical assays reveal that
those SaeS variants have altered autokinase and phosphotransferase activities.
Finally, animal experiments demonstrate that the linker peptide-mediated fine
tuning of SaeS kinase activity is critical for survival of the pathogen. Our
results indicate that the function of the linker peptide in SaeS is a highly
evolved feature with very optimized amino acid sequences, and we propose that, in
other SaeS-like intramembrane sensing histidine kinases, the extracytoplasmic
linker peptides actively fine-control their kinases.
PMID- 25849575
TI - The good, the bad and the ugly of catheterization practice among elite athletes
with spinal cord injury.
PMID- 25849577
TI - Preparation of tertiary amines by the reaction of iminium ions derived from
unsymmetrical aminals with zinc and magnesium organometallics.
AB - We report a convenient one-pot preparation of polyfunctional tertiary amines,
including various biorelevant phenethylamines or ephedrine derivatives, via the
reaction of new functionalized iminium ions with a variety of zinc and magnesium
organometallic reagents. These iminium ions were generated from unsymmetrical
aminals, obtained by the in situ addition of various amides to Tietze's iminium
salt [Me2NCH2(+)CF3COO(-)]. A functionalized aniline, prepared by this method,
was converted to a quinolidine via an intramolecular Heck reaction.
PMID- 25849576
TI - Sex differences in liver toxicity-do female and male human primary hepatocytes
react differently to toxicants in vitro?
AB - There is increasing amount of evidence for sex variation in drug efficiency and
toxicity profiles. Women are more susceptible than men to acute liver injury from
xenobiotics. In general, this is attributed to sex differences at a physiological
level as well as differences in pharmacokinetics and pharmacodynamics, but
neither of these can give a sufficient explanation for the diverse responses to
xenobiotics. Existing data are mainly based on animal models and limited data
exist on in vitro sex differences relevant to humans. To date, male and female
human hepatocytes have not yet been compared in terms of their responses to
hepatotoxic drugs. We investigated whether sex-specific differences in acute
hepatotoxicity can be observed in vitro by comparing hepatotoxic drug effects in
male and female primary human hepatocytes. Significant sex-related differences
were found for certain parameters and individual drugs, showing an overall higher
sensitivity of female primary hepatocytes to hepatotoxicants. Moreover, our work
demonstrated that high content screening is feasible with pooled primary human
hepatocytes in suspension.
PMID- 25849578
TI - Early life origins of all-cause and cause-specific disability pension: findings
from the Helsinki Birth Cohort Study.
AB - BACKGROUND: There is some evidence linking sub-optimal prenatal development to an
increased risk of disability pension (DP). Our aim was to investigate whether
body size at birth was associated with transitioning into all-cause and cause
specific DP during the adult work career. METHODS: 10 682 people born in 1934-44
belonging to the Helsinki Birth Cohort Study had data on birth weight extracted
from birth records, and on time, type and reason of retirement between 1971 and
2011 extracted from the Finnish Centre for Pensions. RESULTS: Altogether 21.3%
transitioned into DP during the 40-year follow-up, mainly due to mental
disorders, musculoskeletal disorders and cardiovascular disease. Average age of
transitioning into DP was 51.3 (SD 8.4) for men and 52.2 (SD 7.6) for women.
Cohort members who did not transition into DP retired 10 years later on average.
Among men, higher birth weight was associated with a lower hazard of
transitioning into DP, adjusted hazard ratio (HR) being 0.94 (95% confidence
interval [CI] 0.88-0.99 for 1 SD increase in birth weight). For DP due to mental
disorders the adjusted HR was 0.90, 95% CI 0.81, 0.99. A similar but non
significant trend was found for DP due to cardiovascular disease. Among women
there were no associations between body size at birth and all-cause DP (p for
interaction gender*birth weight on DP p = 0.007). CONCLUSIONS: Among men
disability pension, particularly due to mental disorders, may have its origins in
prenatal development. Given that those who retire due to mental health problems
are relatively young, the loss to the workforce is substantial.
PMID- 25849579
TI - A transgenic Prox1-Cre-tdTomato reporter mouse for lymphatic vessel research.
AB - The lymphatic vascular system plays an active role in immune cell trafficking,
inflammation and cancer spread. In order to provide an in vivo tool to improve
our understanding of lymphatic vessel function in physiological and pathological
conditions, we generated and characterized a tdTomato reporter mouse and crossed
it with a mouse line expressing Cre recombinase under the control of the
lymphatic specific promoter Prox1 in an inducible fashion. We found that the
tdTomato fluorescent signal recapitulates the expression pattern of Prox1 in
lymphatic vessels and other known Prox1-expressing organs. Importantly, tdTomato
co-localized with the lymphatic markers Prox1, LYVE-1 and podoplanin as assessed
by whole-mount immunofluorescence and FACS analysis. The tdTomato reporter was
brighter than a previously established red fluorescent reporter line. We
confirmed the applicability of this animal model to intravital microscopy of
dendritic cell migration into and within lymphatic vessels, and to fluorescence
activated single cell analysis of lymphatic endothelial cells. Additionally, we
were able to describe the early morphological changes of the lymphatic
vasculature upon induction of skin inflammation. The Prox1-Cre-tdTomato reporter
mouse thus shows great potential for lymphatic research.
PMID- 25849580
TI - Distinct inhibitory effects on mTOR signaling by ethanol and INK128 in diffuse
large B-cell lymphoma.
AB - BACKGROUND: The mechanistic target of rapamycin, (mTOR) kinase plays a pivotal
role in controlling critical cellular growth and survival pathways, and its
aberrant induction is implicated in cancer pathogenesis. Therefore, suppression
of active mTOR signaling has been of great interest to researchers; several mTOR
inhibitors have been discovered to date. Ethanol (EtOH), similar to pharmacologic
mTOR inhibitors, has been shown to suppress the mTOR signaling pathway, though in
a non-catalytic manner. Despite population studies showing that the consumption
of EtOH has a protective effect against hematological malignancies, the
mechanisms behind EtOH's modulation of mTOR activity in cells and its downstream
consequences are largely unknown. Here we evaluated the effects of EtOH on the
mTOR pathway, in comparison to the active-site mTOR inhibitor INK128, and
compared translatome analysis of their downstream effects in diffuse large B-cell
lymphoma (DLBCL). RESULTS: Treatment of DLBCL cells with EtOH suppressed mTORC1
complex formation while increasing AKT phosphorylation and mTORC2 complex
assembly. INK128 completely abrogated AKT phosphorylation without affecting the
structure of mTORC1/2 complexes. Accordingly, EtOH less profoundly suppressed cap
dependent translation and global protein synthesis, compared to a remarkable
inhibitory effect of INK128 treatment. Importantly, EtOH treatment induced the
formation of stress granules, while INK128 suppressed their formation. Microarray
analysis of polysomal RNA revealed that although both agents primarily affected
cell growth and survival, EtOH and INK128 regulated the synthesis of mostly
distinct genes involved in these processes. Though both EtOH and INK128 inhibited
cell cycle, proliferation and autophagy, EtOH, in contrast to INK128, did not
induce cell apoptosis. CONCLUSION: Given that EtOH, similar to pharmacologic mTOR
inhibitors, inhibits mTOR signaling, we systematically explored the effect of
EtOH and INK128 on mTOR signal transduction, components of the mTORC1/2
interaction and their downstream effectors in DLBCL malignancy. We found that
EtOH partially inhibits mTOR signaling and protein translation, compared to
INK128's complete mTOR inhibition. Translatome analysis of mTOR downstream target
genes established that differential inhibition of mTOR by EtOH and INK128
distinctly modulates translation of specific subsets of mRNAs involved in cell
growth and survival, leading to differential cellular response and survival.
PMID- 25849581
TI - Quantitative amyloid imaging using image-derived arterial input function.
AB - Amyloid PET imaging is an indispensable tool widely used in the investigation,
diagnosis and monitoring of Alzheimer's disease (AD). Currently, a reference
region based approach is used as the mainstream quantification technique for
amyloid imaging. This approach assumes the reference region is amyloid free and
has the same tracer influx and washout kinetics as the regions of interest.
However, this assumption may not always be valid. The goal of this work is to
evaluate an amyloid imaging quantification technique that uses arterial region of
interest as the reference to avoid potential bias caused by specific binding in
the reference region. 21 participants, age 58 and up, underwent Pittsburgh
compound B (PiB) PET imaging and MR imaging including a time-of-flight (TOF) MR
angiography (MRA) scan and a structural scan. FreeSurfer based regional analysis
was performed to quantify PiB PET data. Arterial input function was estimated
based on coregistered TOF MRA using a modeling based technique. Regional
distribution volume (VT) was calculated using Logan graphical analysis with
estimated arterial input function. Kinetic modeling was also performed using the
estimated arterial input function as a way to evaluate PiB binding (DVRkinetic)
without a reference region. As a comparison, Logan graphical analysis was also
performed with cerebellar cortex as reference to obtain DVRREF. Excellent
agreement was observed between the two distribution volume ratio measurements
(r>0.89, ICC>0.80). The estimated cerebellum VT was in line with literature
reported values and the variability of cerebellum VT in the control group was
comparable to reported variability using arterial sampling data. This study
suggests that image-based arterial input function is a viable approach to
quantify amyloid imaging data, without the need of arterial sampling or a
reference region. This technique can be a valuable tool for amyloid imaging,
particularly in population where reference normalization may not be accurate.
PMID- 25849582
TI - One-pot, three-component approach to the synthesis of 3,4,5-trisubstituted
pyrazoles.
AB - An operationally simple and high yielding protocol for the synthesis of
polyfunctional pyrazoles has been developed through one-pot, three-component
coupling of aldehydes, 1,3-dicarbonyls, and diazo compounds as well as tosyl
hydrazones. The reaction proceeds through a tandem Knoevenagel condensation, 1,3
dipolar cycloaddition, and transition metal-free oxidative aromatization reaction
sequence utilizing molecular oxygen as a green oxidant. The scope of the reaction
was studied by varying the aldehyde, 1,3-dicarbonyl, and diazo component
individually.
PMID- 25849584
TI - Determination of solid state characteristics of spray-congealed Ibuprofen solid
lipid microparticles and their impact on sustaining drug release.
AB - This study was used to find solid state characteristics of ibuprofen loaded spray
congealed solid lipid microparticles (SLMs) by employing simple lipids as
matrices, with or without polymeric additives, and the impact of solid drug
matrix miscibility on sustaining drug release. Solid miscibility of ibuprofen
with two lipids, cetyl alcohol (CA) and stearic acid (SA), were investigated
using differential scanning calorimetry (DSC). SLMs containing 20% w/w ibuprofen
with or without polymeric additives, PVP/VA and EC, were produced by spray
congealing, and the resultant microparticles were subjected to visual examination
by scanning electron microscopy (SEM), thermal analysis using DSC, and hot-stage
microscopy. Intermolecular interactions between lipids and drug as well as
additives were investigated by Fourier-transformed infrared spectroscopy (FTIR)
and nuclear magnetic resonance spectroscopy (NMR). X-ray diffractometry (XRD) was
utilized to study polymorphic changes of drug and matrix over the course of a
year. Ibuprofen was found to depress the melting points of CA and SA in a
colligative manner, reaching maximum solubility at 10% w/w and 30% w/w for CA and
SA, respectively. Drug encapsulation efficiencies and yields of spray-congealed
SLMs containing 20% w/w ibuprofen were consistently high for both lipid matrices.
CA and SA were found to adopt their stable gamma- and beta-polymorphs,
respectively, immediately after spray congealing. The spray congealing process
resulted in ibuprofen adopting an amorphous or poorly crystalline state, with no
further changes over the course of a year. SEM, DSC, and hot stage microscope
studies on the SLMs confirmed the formation of a solid dispersion between
ibuprofen and CA and a solid solution between ibuprofen and SA. SA was found to
sustain the release of ibuprofen significantly better than CA. PVP/VA and EC
showed some interactions with CA, which led to an expansion of unit cell
dimensions of CA upon spray congealing, whereas they showed negligible
interactions with SA. PVP/VA and EC both hastened drug release in both CA and SA
matrices, despite PVP/VA being hydrophilic and EC being hydrophobic. CA and SA
are useful as lipid matrices that do not exhibit polymorphism when spray
congealed. Sustained release of ibuprofen was achieved with the formation of a
solid solution with SA. Solid miscibility of drug in lipid matrix has a large
impact on the ability of the SLMs to sustain the release of a drug. Polymeric
additives generally disrupted structural integrity of SLMs and led to faster drug
release.
PMID- 25849583
TI - Paraptosis cell death induction by the thiamine analog benfotiamine in leukemia
cells.
AB - Benfotiamine is a synthetic thiamine analogue that stimulates transketolase, a
cellular enzyme essential for glucose metabolism. Currently, benfotiamine is used
to treat diabetic neuropathy. We recently reported that oral benfotiamine induced
a temporary but remarkable recovery from acute myeloid leukemia in an elderly
patient who was ineligible for standard chemotherapy due to dementia and renal
failure. In the present study we present evidences that benfotiamine possess
antitumor activity against leukemia cells. In a panel of nine myeloid leukemia
cell lines benfotiamine impaired the viability of HL-60, NB4, K562 and KG1 cells
and also inhibited the growing of primary leukemic blasts. The antitumor activity
of benfotiamine is not mediated by apoptosis, necrosis or autophagy, but rather
occurs though paraptosis cell death induction. Mechanistic studies revealed that
benfotiamine inhibited the activity of constitutively active ERK1/2 and
concomitantly increased the phosphorylation of JNK1/2 kinase in leukemic cells.
In addition, benfotiamine induced the down regulation of the cell cycle regulator
CDK3 which resulted in G1 cell cycle arrest in the sensitive leukemic cells.
Moreover, combination index studies showed that benfotiamine enhanced the
antiproliferative activities of cytarabine against leukemia cells. These findings
suggest that benfotiamine has antitumor therapeutic potential.
PMID- 25849585
TI - Measurement of glycolysis reactants by high-throughput solid phase extraction
with tandem mass spectrometry: Characterization of pyrophosphate-dependent
phosphofructokinase as a case study.
AB - Glycolysis is a 10-step metabolic pathway involved in producing cellular energy.
Many tumors exhibit accelerated glycolytic rates, and enzymes that participate in
this pathway are focal points of cancer research. Here, a novel method for the
measurement of glycolysis reactants from in vitro samples is presented. Fast and
direct measurement is achieved by an automated system that couples on-line solid
phase extraction (SPE) with tandem mass spectrometry (MS/MS). The single
analytical method enables multiple reactants to be measured concurrently,
sustains a cycle time of 8s, and permits the measurement of up to 10,000 samples
per day. Concentration-response curves were conducted using standards for 10
metabolic intermediates, and the results demonstrate that the detection strategy
has excellent sensitivity (average limit of detection = 5.4 nM), dynamic range
(nanomolar to micromolar), and linear response (average R(2) = 0.998). To test
the analysis method on reactions, pyrophosphate-dependent phosphofructokinase
(PPi-PFK) was used as a model system. Data that corroborate the activation and
inhibition of PPi-PFK are presented, and the ways in which SPE-MS/MS simplifies
experimental design and interpretation are highlighted. In summary, the method
for measuring metabolic intermediates described here demonstrates unprecedented
speed, performance, and versatility.
PMID- 25849586
TI - Cell fate reprogramming by control of intracellular network dynamics.
AB - Identifying control strategies for biological networks is paramount for practical
applications that involve reprogramming a cell's fate, such as disease
therapeutics and stem cell reprogramming. Here we develop a novel network control
framework that integrates the structural and functional information available for
intracellular networks to predict control targets. Formulated in a logical
dynamic scheme, our approach drives any initial state to the target state with
100% effectiveness and needs to be applied only transiently for the network to
reach and stay in the desired state. We illustrate our method's potential to find
intervention targets for cancer treatment and cell differentiation by applying it
to a leukemia signaling network and to the network controlling the
differentiation of helper T cells. We find that the predicted control targets are
effective in a broad dynamic framework. Moreover, several of the predicted
interventions are supported by experiments.
PMID- 25849587
TI - Prevalence and predictors of asymptomatic malaria parasitemia among pregnant
women in the rural surroundings of Arbaminch Town, South Ethiopia.
AB - BACKGROUND: In Sub-Saharan African countries, including Ethiopia, malaria in
pregnancy is a major public health threat which results in significant
morbidities and mortalities among pregnant women and their fetuses. In malaria
endemic areas, Plasmodium infections tend to remain asymptomatic yet causing
significant problems like maternal anemia, low birth weight, premature births,
and still birth. This study was conducted to determine the prevalence and
predictors of asymptomatic Plasmodium infection among pregnant women in the rural
surroundings of Arba Minch Town, Southern Ethiopia. METHODS: A community based
cross-sectional study comprising multistage sampling was conducted between April
and June, 2013. Socio-demographic data were collected by using a semi-structured
questionnaire. Plasmodium infection was diagnosed by using Giemsa-stained blood
smear microscopy and a rapid diagnostic test (SD BIOLINE Malaria Ag Pf/Pv POCT,
standard diagnostics, inc., Korea). RESULTS: Of the total 341 pregnant women
participated in this study, 9.1% (31/341) and 9.7% (33/341) were confirmed to be
infected with Plasmodium species by microscopy and rapid diagnostic tests (RDTs),
respectively. The geometric mean of parasite density was 2392 parasites per
microliter (MUl); 2275/ MUl for P. falciparum and 2032/ MUl for P. vivax.
Parasitemia was more likely to occur in primigravidae (Adjusted odds ratio (AOR):
9.4, 95% confidence interval (CI): 4.3-60.5), secundigravidae (AOR: 6.3, 95% CI:
2.9-27.3), using insecticide treated bed net (ITN) sometimes (AOR: 3.2, 95% CI:
1.8- 57.9), not using ITN at all (AOR: 4.6, 95% CI: 1.4-14.4) compared to
multigravidae and using ITN always, respectively. CONCLUSION: Asymptomatic
malaria in this study is low compared to other studies' findings. Nevertheless,
given the high risk of malaria during pregnancy, pregnant women essentially be
screened for asymptomatic Plasmodium infection and be treated promptly via the
antenatal care (ANC) services.
PMID- 25849588
TI - Loss-of-function analysis reveals distinct requirements of the translation
initiation factors eIF4E, eIF4E-3, eIF4G and eIF4G2 in Drosophila
spermatogenesis.
AB - In eukaryotes, post-transcriptional regulation of gene expression has a key role
in many cellular and developmental processes. Spermatogenesis involves a complex
developmental program that includes changes in cell cycle dynamics and dramatic
cellular remodeling. Translational control is critical for spermatogenesis in
Drosophila as many mRNAs synthesized in the spermatocytes are translated only
much later during spermatid differentiation. Testes-specific translation
initiation factors eIF4E-3 and eIF4G2 are essential specifically for male
fertility. However, details of their roles during different stages of
spermatogenesis are unknown, and the role of canonical translation initiation
factors in spermatogenesis remains unexplored. In this study, we addressed the
functional role of eIF4E-1, eIF4E-3, eIF4G and eIF4G2 in testes development and
formation of mature sperm. Using the UAS-Gal4 system and RNA interference, we
systematically knocked down these four genes in different stages of germ cell
development, and in the somatic cells. Our results show that eIF4E-1 function in
early germ cells and the surrounding somatic cells is critical for
spermatogenesis. Both eIF4E-1 and eIF4E-3 are required in spermatocytes for
chromosome condensation and cytokinesis during the meiotic stages. Interestingly,
we find that eIF4G knockdown did not affect male fertility while eIF4G2 has
distinct functions during spermatogenesis; it is required in early germ cells for
proper meiotic divisions and spermatid elongation while its abrogation in
spermatocytes caused meiotic arrest. Double knockdown of eIF4G and eIF4G2 shows
that these proteins act redundantly during the early stages of spermatogenesis.
Taken together, our analysis reveals spatio-temporal roles of the canonical and
testes-specific translation initiation factors in coordinating developmental
programs during spermatogenesis.
PMID- 25849589
TI - Genome-wide analysis of the AP2/ERF family in Eucalyptus grandis: an intriguing
over-representation of stress-responsive DREB1/CBF genes.
AB - BACKGROUND: The AP2/ERF family includes a large number of developmentally and
physiologically important transcription factors sharing an AP2 DNA-binding
domain. Among them DREB1/CBF and DREB2 factors are known as master regulators
respectively of cold and heat/osmotic stress responses. EXPERIMENTAL APPROACHES:
The manual annotation of AP2/ERF family from Eucalyptus grandis, Malus, Populus
and Vitis genomes allowed a complete phylogenetic study for comparing the
structure of this family in woody species and the model Arabidopsis thaliana.
Expression profiles of the whole groups of EgrDREB1 and EgrDREB2 were
investigated through RNAseq database survey and RT-qPCR analyses. RESULTS: The
structure and the size of the AP2/ERF family show a global conservation for the
plant species under comparison. In addition to an expansion of the ERF subfamily,
the tree genomes mainly differ with respect to the group representation within
the subfamilies. With regard to the E. grandis DREB subfamily, an obvious feature
is the presence of 17 DREB1/CBF genes, the maximum reported to date for
dicotyledons. In contrast, only six DREB2 have been identified, which is similar
to the other plants species under study, except for Malus. All the DREB1/CBF and
DREB2 genes from E. grandis are expressed in at least one condition and all are
heat-responsive. Regulation by cold and drought depends on the genes but is not
specific of one group; DREB1/CBF group is more cold-inducible than DREB2 which is
mainly drought responsive. CONCLUSION: These features suggest that the dramatic
expansion of the DREB1/CBF group might be related to the adaptation of this
evergreen tree to climate changes when it expanded in Australia.
PMID- 25849591
TI - Compositional engineering of perovskite oxides for highly efficient oxygen
reduction reactions.
AB - Mixed conducting perovskite oxides are promising catalysts for high-temperature
oxygen reduction reaction. Pristine SrCoO(3-delta) is a widely used parent oxide
for the development of highly active mixed conductors. Doping a small amount of
redox-inactive cation into the B site (Co site) of SrCoO(3-delta) has been
applied as an effective way to improve physicochemical properties and
electrochemical performance. Most findings however are obtained only from
experimental observations, and no universal guidelines have been proposed. In
this article, combined experimental and theoretical studies are conducted to
obtain fundamental understanding of the effect of B-site doping concentration
with redox-inactive cation (Sc) on the properties and performance of the
perovskite oxides. The phase structure, electronic conductivity, defect
chemistry, oxygen reduction kinetics, oxygen ion transport, and electrochemical
reactivity are experimentally characterized. In-depth analysis of doping level
effect is also undertaken by first-principles calculations. Among the
compositions, SrCo0.95Sc0.05O(3-delta) shows the best oxygen kinetics and
corresponds to the minimum fraction of Sc for stabilization of the oxygen-vacancy
disordered structure. The results strongly support that B-site doping of SrCoO(3
delta) with a small amount of redox-inactive cation is an effective strategy
toward the development of highly active mixed conducting perovskites for
efficient solid oxide fuel cells and oxygen transport membranes.
PMID- 25849590
TI - TGF-beta1-mediated differentiation of fibroblasts is associated with increased
mitochondrial content and cellular respiration.
AB - OBJECTIVS: Cytokine-dependent activation of fibroblasts to myofibroblasts, a key
event in fibrosis, is accompanied by phenotypic changes with increased secretory
and contractile properties dependent on increased energy utilization, yet changes
in the energetic profile of these cells are not fully described. We hypothesize
that the TGF-beta1-mediated transformation of myofibroblasts is associated with
an increase in mitochondrial content and function when compared to naive
fibroblasts. METHODS: Cultured NIH/3T3 mouse fibroblasts treated with TGF-beta1,
a profibrotic cytokine, or vehicle were assessed for transformation to
myofibroblasts (appearance of alpha-smooth muscle actin [alpha-SMA] stress
fibers) and associated changes in mitochondrial content and functions using laser
confocal microscopy, Seahorse respirometry, multi-well plate reader and
biochemical protocols. Expression of mitochondrial-specific proteins was
determined using western blotting, and the mitochondrial DNA quantified using
Mitochondrial DNA isolation kit. RESULTS: Treatment with TGF-beta1 (5 ng/mL)
induced transformation of naive fibroblasts into myofibroblasts with a threefold
increase in the expression of alpha-SMA (6.85 +/- 0.27 RU) compared to cells not
treated with TGF-beta1 (2.52 +/- 0.11 RU). TGF-beta1 exposure increased the
number of mitochondria in the cells, as monitored by membrane potential sensitive
dye tetramethylrhodamine, and expression of mitochondria-specific proteins;
voltage-dependent anion channels (0.54 +/- 0.05 vs. 0.23 +/- 0.05 RU) and adenine
nucleotide transporter (0.61 +/- 0.11 vs. 0.22 +/- 0.05 RU), as well as
mitochondrial DNA content (530 +/- 12 MUg DNA/106 cells vs. 307 +/- 9 MUg DNA/106
cells in control). TGF-beta1 treatment was associated with an increase in
mitochondrial function with a twofold increase in baseline oxygen consumption
rate (2.25 +/- 0.03 vs. 1.13 +/- 0.1 nmol O2/min/106 cells) and FCCP-induced
mitochondrial respiration (2.87 +/- 0.03 vs. 1.46 +/- 0.15 nmol O2/min/106
cells). CONCLUSIONS: TGF-beta1 induced differentiation of fibroblasts is
accompanied by energetic remodeling of myofibroblasts with an increase in
mitochondrial respiration and mitochondrial content.
PMID- 25849592
TI - Is psychiatry only neurology? Or only abnormal psychology? Deja vu after 100
years.
AB - Forgetting history, which frequently repeats itself, is a mistake. In General
Psychopathology, Jaspers criticised early 20th century psychiatrists, including
those who thought psychiatry was only neurology (Wernicke) or only abnormal
psychology (Freud), or who did not see the limitations of the medical model in
psychiatry (Kraepelin). Jaspers proposed that some psychiatric disorders follow
the medical model (Group I), while others are variations of normality (Group
III), or comprise schizophrenia and severe mood disorders (Group II). In the
early 21st century, the players' names have changed but the game remains the
same. The US NIMH is reprising both Wernicke's brain mythology and Kraepelin's
marketing promises. The neo-Kraepelinian revolution started at Washington
University, became pre-eminent through the DSM-III developed by Spitzer, but
reached a dead end with the DSM-5. McHugh, who described four perspectives in
psychiatry, is the leading contemporary representative of the Jaspersian
diagnostic approach. Other neo-Jaspersians are: Berrios, Wiggins and Schwartz,
Ghaemi, Stanghellini, Parnas and Sass. Can psychiatry learn from its mistakes?
The current psychiatric language, organised at its three levels, symptoms,
syndromes, and disorders, was developed in the 19th century but is obsolete for
the 21st century. Scientific advances in Jaspers' Group III disorders require
collaborating with researchers in the social and psychological sciences. Jaspers'
Group II disorders, redefined by the author as schizophrenia, catatonic
syndromes, and severe mood disorders, are the core of psychiatry. Scientific
advancement in them is not easy because we are not sure how to delineate between
and within them correctly.
PMID- 25849593
TI - Correction: imatinib ameliorates neuroinflammation in a rat model of multiple
sclerosis by enhancing blood-brain barrier integrity and by modulating the
peripheral immune response.
PMID- 25849594
TI - Exploring how pain leads to productivity loss in primary care consulters for
osteoarthritis: a prospective cohort study.
AB - OBJECTIVE: Osteoarthritis pain has become a leading cause of decreased
productivity and work disability in older workers, a major concern in primary
care. How osteoarthritis pain leads to decreased productivity at work is unclear;
the aim of this study was to elucidate causal mechanisms and thus identify
potential opportunities for intervention. METHODS: Population-based prospective
cohort study of primary care consulters with osteoarthritis. Path analysis was
used to test proposed mechanisms by examining the association between pain at
baseline, and onset of work productivity loss at three years for mediation by
physical limitation, depression, poor sleep and poor coping mechanisms. RESULTS:
High pain intensity was associated with onset of work productivity loss (Adjusted
Odds Ratio 2.5; 95%CI 1.3, 4.8). About half of the effect of pain on work
productivity was a direct effect, and half was mediated by the impact of pain on
physical function. Depression, poor sleep quality and poor coping did not mediate
the association between high pain intensity and onset of work productivity loss.
CONCLUSIONS: As pain is a major cause of work productivity loss, results suggest
that decreasing pain should be a major focus. However, successfully improving
function may have an indirect effect by decreasing the impact of pain on work
productivity, especially important as significant pain reduction is often
difficult to achieve. Although depression, sleep problems, and coping strategies
may be directly related to work productivity loss, addressing these issues may
not have much effect on the significant impact of pain on work productivity.
PMID- 25849595
TI - LAPTM4B-35, a cancer-related gene, is associated with poor prognosis in TNM
stages I-III gastric cancer patients.
AB - BACKGROUND: Lysosome-associated transmembrane protein 4beta-35 (LAPTM4B-35), a
member of the mammalian 4-tetratransmembrane spanning protein superfamily, has
been reported to be overexpressed in several cancers. However the expression of
LAPTM4B-35 and its role in the progression of gastric cancer (GC) remains
unknown. The aim of this study was to investigate LAPTM4B-35 expression in GC,
its potential relevance to clinicopathologic parameters and role of LAPTM4B-35
during gastric carcinogenesis. METHODS: In the present study, paraffin-embedded
specimens with GC (n = 240, including 180 paired specimens) and 24 paired fresh
frozen tissues were analyzed. qRT-PCR and immunohistochemistry (IHC) were used to
analyze the expression of LAPTM4B-35 in GC. The effects of LAPTM4B-35 on GC cell
proliferation, migration and invasion were determined by overexpression and
knockdown assays. RESULTS: IHC showed that LAPTM4B-35 was expressed in 68.3%
(123/180) of GC tissues, while in 16.1% (29/180) of their paired adjacent
noncancerous gastric tissues (P = 0.000). LAPTM4B-35 mRNA levels in GC tissues
were also significantly elevated when compared with their paired adjacent
noncancerous tissues (P = 0.017). Overexpression of LAPTM4B-35 was significantly
associated with degree of differentiation, depth of invasion, lymphovascular
invasion and lymph node metastasis (P<0.05). Kaplan-Meier survival curves
revealed that patients with LAPTM4B-35 expression had a significant decrease in
overall survival (OS) in stages I-III GC patients (P = 0.006). Multivariate
analysis showed high expression of LAPTM4B-35 was an independent prognostic
factor for OS in stage I-III GC patients (P = 0.025). CONCLUSION: These findings
indicate that LAPTM4B-35 overexpression may be related to GC progression and poor
prognosis, and thus may serve as a new prediction marker of prognosis in GC
patients.
PMID- 25849597
TI - Role of adiponectin and free fatty acids on the association between abdominal
visceral fat and insulin resistance.
AB - BACKGROUND: Experimental studies have shown that high free fatty acid (FFA) and
low adiponectin (ADIPO) levels are involved in the mechanisms by which adiposity
promotes insulin resistance (IR). However, no previous clinical studies have
simultaneously analysed the relative contribution of FFA and ADIPO levels on the
relation of abdominal visceral fat (AVF) with insulin resistance. OBJECTIVE: To
analyse the contribution of low ADIPO (adiponectin < =p25th: 8.67 MUg/mL in women
and 5.30 MUg/mL in men), and high FFAs (FFAs > =p75th: 0.745 mEq/L in women and
0.60 mEq/L in men) to the association of high AVF (AVF > =p75th: 127 cm2 in
women; 152.7 cm2 in men) with insulin resistance (HOMA-IR > =75th: 3.58 in women
and 3.12 in men), in non-diabetic subjects. MATERIAL AND METHODS: A cross
sectional analysis was performed including 1217 control participants of the
Genetics of Atherosclerotic Disease study (GEA). Clinical, tomographic and
biochemical parameters were measured in all participants. Logistic regression
models were used to assess the association of high AVF with IR stratifying
according to gender, and to normal or low ADIPO and normal or high FFA serum
levels. RESULTS: In comparison to referent group, in men low ADIPO unlike high
FFA increased the risk of IR. Females with normal AVF and low ADIPO, or high AVF
and normal ADIPO had aprox 3 folds risk of IR (OR [IC95%]: 3.7 [2.1-6.6], p <
0.001, and 3.4 [2.0-5.7], p < 0.001; respectively). The risk increased to 7.6
[4.2-13.8], p < 0.001 when high AVF and low ADIPO were present. Irrespective of
AVF, the effect of low ADIPO on IR was higher than that seen for high FFA.
Besides, our results suggest an additive effect of high AVF, high FFA and low
ADIPO on the IR prevalence. CONCLUSIONS: The present study provides novel and
important information about the combined effect of high AVF and low ADIPO on the
risk of IR. Furthermore, our data suggest that the effect of low adiponectin
levels on the high AVF-IR association is stronger than that observed for high
FFA, suggesting that adiponectin could be used as biomarker to identify subjects
at high risk for T2DM and CAD.
PMID- 25849598
TI - Expression of CDK1(Tyr15), pCDK1(Thr161), Cyclin B1 (total) and pCyclin
B1(Ser126) in vulvar squamous cell carcinoma and their relations with
clinicopatological features and prognosis.
AB - Cyclin B1-CDK1 complex plays an important role in the regulation of cell cycle.
Activation of Cyclin B1 and CDK1 and the formation of the complex in G2/M are
under multiple regulations involving many regulators such as isoforms of 14-3-3
and CDC25 and Wee1. Abnormal expression of Cyclin B1 and CDK1 has been detected
in various tumors. However, to our knowledge no previous study has investigated
Cyclin B1 and CDK1 in vulvar cancer. Therefore, we evaluated the statuses of
CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total) and pCyclin B1Ser126 in 297 cases of
vulvar squamous cell carcinomas by immunohistochemistry. Statistical analyses
were performed to explore their clinicopathological and prognostic values. In at
least 25% of tumor cases high expression of CDK1Tyr15, pCDK1Thr161, Cyclin B1
(total) and pCyclin B1Ser126 was observed, compared to the low levels in normal
vulvar squamous epithelium. Elevated levels of CDK1Tyr15, pCDK1Thr161, Cyclin B1
(total) and pCyclin B1Ser126 were correlated with advanced tumor behaviors and
aggressive features. Although CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total) and
pCyclin B1Ser126 could not be identified as prognostic factors, combinations of
(pCDK1Thr161 C+N + 14-3-3sigmaN), (pCDK1Thr161 C+N + 14-3-3etaC), (pCDK1Thr161
C+N + Wee1C) and (pCDK1Thr161 C+N + 14-3-3sigmaN + 14-3-3etaC + Wee1C) were
correlated with disease-specific survival (p = 0.036, p = 0.029, p = 0.042 and p
= 0.007, respectively) in univariate analysis. The independent prognostic
significance of (pCDK1Thr161 C+N + 14-3-3sigmaN + 14-3-3etaC + Wee1C) was
confirmed by multivariate analysis. In conclusion, CDK1Tyr15, pCDK1Thr161, Cyclin
B1 (total) and pCyclin B1Ser126 may be involved in progression of vulvar squamous
cell carcinoma. The combination of pCDK1Thr161, 14-3-3sigma, 14-3-3eta and Wee1
was a statistically independent prognostic factor.
PMID- 25849599
TI - Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia
Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on
Safety and Outcomes.
AB - PURPOSE: We evaluated photoselective vaporization of the prostate using the
GreenLightTM XPSTM 180 W system for benign prostatic hyperplasia treatment in a
large multi-institutional cohort at 2 years. We particularly examined safety,
outcomes and the re-treatment rate in larger prostates, defined as a prostate
volume of 80 cc or greater, to assess the potential of photoselective
vaporization of the prostate as a size independent procedure. MATERIALS AND
METHODS: A total of 1,196 patients were treated at 6 international centers in
Canada, the United States, France and England. All parameters were collected
retrospectively, including complications, I-PSS, maximum urinary flow rate, post
void residual urine, prostate volume, prostate specific antigen and the
endoscopic re-intervention rate. Subgroup stratified comparative analysis was
performed according to preoperative prostate volume less than 80 vs 80 cc or
greater on transrectal ultrasound. RESULTS: Median prostate size was 50 cc in 387
patients and 108 cc in 741 in the prostate volume groups less than 80 and 80 cc
or greater, respectively. The rate of conversion to transurethral prostate
resection was significantly higher in the 80 cc or greater group than in the less
than 80 cc group (8.4% vs 0.6%, p <0.01). I-PSS, quality of life score, maximum
urinary flow rate and post-void residual urine were significantly improved
compared to baseline at 6, 12 and 24 months of followup without significant
differences between the prostate size groups. The re-treatment rate at 2 years
reported in 5 of 411 patients was associated with the delivery of decreased
energy density (2.1 vs 4.4 kJ/cc) in the group without re-treatment. CONCLUSIONS:
Photoselective vaporization of the prostate using the XPS 180 W system is safe
and efficacious, providing durable improvement in functional outcomes at 2 years
independent of prostate size when treated with sufficient energy.
PMID- 25849600
TI - Primary Endoscopic Realignment of Urethral Disruption Injuries--A Double-Edged
Sword?
AB - PURPOSE: Controversy remains regarding initial management of traumatic urethral
disruption injuries. We evaluated the outcomes of primary endoscopic realignment
vs suprapubic tube placement in this patient population. MATERIALS AND METHODS:
We reviewed our urological trauma database for patients with blunt trauma related
posterior urethral injuries from 2000 to 2014. Patients underwent primary
endoscopic realignment or suprapubic tube placement alone. The primary outcome
was the success of primary realignment, defined as no further need for urological
intervention. Secondary outcomes were the need for endoscopic interventions
and/or urethroplasty, time to urethroplasty, urethroplasty success and long-term
functional outcomes. RESULTS: A total of 27 patients underwent primary
realignment and 14 underwent suprapubic tube placement. Mean followup was 40
months (median 24, range 1 to 152). Realignment was successful in 10 patients
(37%) at a mean followup of 67.3 weeks (median 27.3, range 4 to 284). In the 17
cases (63%) that failed mean time to failure was 9.7 weeks (median 8.5, range 1
to 26). Seven patients (26%) treated with realignment and 11 (79%) with a
suprapubic tube proceeded to urethroplasty. Mean +/- SD time to urethroplasty was
significantly shorter in the suprapubic tube group (14.6 +/- 7.6 vs 5.8 +/- 1.6
months, p = 0.003). There was no difference in operative time, complications,
success or functional outcomes. CONCLUSIONS: Management of traumatic urethral
disruption injuries by primary endoscopic realignment serves as definitive
therapy in more than a third of treated patients. It prevents the need for formal
urethroplasty in more than half of failed cases.
PMID- 25849601
TI - The Effects of RAAS Inhibition in Rate Limiting Step by Aliskiren on Testicular
Torsion Injury in Rats.
AB - PURPOSE: Testicular torsion is a urological emergency. Failure of timely
intervention for this issue leads the testicles to go into necrosis. If left
untreated, it can lead to loss of the reproductive organs. The aim of this study
was to examine the role of aliskiren in testicular torsion and detorsion
injuries. MATERIALS AND METHODS: Rats were divided into 8 groups of 12 each,
including no torsion-detorsion, no torsion-detorsion plus 200 mg/kg aliskiren
orally, torsion, torsion-detorsion, torsion plus 100 mg/kg aliskiren orally,
torsion plus 200 mg/kg aliskiren orally, torsion-detorsion plus 100 mg/kg
aliskiren orally and torsion-detorsion plus 200 mg/kg aliskiren orally. Aliskiren
was administered 30 minutes before ischemia and reperfusion, and also 24 hours
before the experimental protocol in all treatment groups. Ischemia and
reperfusion were each applied for 2 hours. RESULTS: Testicular damage decreased
superoxide dismutase and glutathione, and increased malondialdehyde in the testis
tissues of rats. Aliskiren administration increased superoxide dismutase and
glutathione, and decreased malondialdehyde in the testis tissues. Values were
measured by a biochemical autoanalyzer. In addition, this torsion-detorsion
damage caused a significant increase in levels of the inflammatory cytokine and
agents interleukin-1beta and inducible nitric oxide synthase, as examined by real
time polymerase chain reaction. Aliskiren administration decreased these
parameters. On pathological evaluation administration of a 200 mg/kg dose of
aliskiren was found to protect the testis. Renin-angiotensin-aldosterone system
inhibition by aliskiren caused an increase in serum renin levels and a decrease
in serum angiotensin II levels. CONCLUSIONS: It appears that aliskiren protects
the testis from ischemia-reperfusion damage by regulating inflammation and the
oxidant-antioxidant balance via renin-angiotensin-aldosterone system inhibition.
PMID- 25849603
TI - Trends in Toilet Training and Voiding Habits among Children with Down Syndrome.
AB - PURPOSE: Children with Down syndrome are at risk for lower urinary tract
dysfunction and delayed toilet training. Comparative studies regarding voiding
function in the Down syndrome population are lacking. We assessed urinary
continence and voiding function in patients with Down syndrome and a control
group. MATERIALS AND METHODS: A questionnaire designed to assess toilet training,
continence status, symptoms of lower urinary tract dysfunction and prior
evaluation of urological complaints was sent to parents of 326 children with Down
syndrome who had been seen at our institution previously. The same survey was
administered to parents of patients without Down syndrome. Data were compiled,
and descriptive and comparative statistical analyses were performed. RESULTS: A
total of 77 patients comprised the Down syndrome group and 78 patients without
Down syndrome comprised the control group. Average age of reported toilet
training completion was 5.5 years in children with Down syndrome and 2.2 years in
controls. Of children 5 years or older 79% with Down syndrome were toilet
trained, compared to 100% of those without Down syndrome. Incontinence was
reported in 46% of previously toilet trained children with Down syndrome and
24.5% of controls. These findings were statistically significant. No significant
difference was observed in the rate of urinary tract infection, symptoms of lower
urinary tract dysfunction or evaluation for urological complaints. CONCLUSIONS:
Children with Down syndrome can experience marked delay in toilet training and
are more likely to suffer incontinence afterward. This study was ineffective in
determining whether symptoms of lower urinary tract dysfunction could be related
to decreased continence rates.
PMID- 25849602
TI - Gleason 6 Prostate Cancer: Translating Biology into Population Health.
AB - PURPOSE: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men
with prostate specific antigen screening, the most histologically well
differentiated and is associated with the most favorable prognosis. Despite its
prevalence, considerable debate exists regarding the genetic features, clinical
significance, natural history, metastatic potential and optimal management.
MATERIALS AND METHODS: Members of the Young Urologic Oncologists in the Society
of Urologic Oncology cooperated in a comprehensive search of the peer reviewed
English medical literature on Gleason 6 prostate cancer, specifically focusing on
the history of the Gleason scoring system, histological features, clinical
characteristics, practice patterns and outcomes. RESULTS: The Gleason scoring
system was devised in the early 1960s, widely adopted by 1987 and revised in 2005
with a more restrictive definition of Gleason 6 disease. There is near consensus
that Gleason 6 meets pathological definitions of cancer, but controversy about
whether it meets commonly accepted molecular and genetic criteria of cancer.
Multiple clinical series suggest that the metastatic potential of contemporary
Gleason 6 disease is negligible but not zero. Population based studies in the
U.S. suggest that more than 90% of men newly diagnosed with prostate cancer
undergo treatment and are exposed to the risk of morbidity for a cancer unlikely
to cause symptoms or decrease life expectancy. Efforts have been proposed to
minimize the number of men diagnosed with or treated for Gleason 6 prostate
cancer. These include modifications to prostate specific antigen based screening
strategies such as targeting high risk populations, decreasing the frequency of
screening, recommending screening cessation, incorporating remaining life
expectancy estimates, using shared decision making and novel biomarkers, and
eliminating prostate specific antigen screening entirely. Large nonrandomized and
randomized studies have shown that active surveillance is an effective management
strategy for men with Gleason 6 disease. Active surveillance dramatically reduces
the number of men undergoing treatment without apparent compromise of cancer
related outcomes. CONCLUSIONS: The definition and clinical relevance of Gleason 6
prostate cancer have changed substantially since its introduction nearly 50 years
ago. A high proportion of screen detected cancers are Gleason 6 and the
metastatic potential is negligible. Dramatically reducing the diagnosis and
treatment of Gleason 6 disease is likely to have a favorable impact on the net
benefit of prostate cancer screening.
PMID- 25849604
TI - A systematic review of transitions between cigarette and smokeless tobacco
product use in the United States.
AB - BACKGROUND: Smokeless tobacco use is becoming an increasingly important public
health issue in the US and may influence cigarette smoking behavior. Systematic
information on transitions between smokeless tobacco and cigarette use in the US
is limited. METHODS: We conducted a systematic review of published literature on
transitions between smokeless tobacco and cigarette use in the US. We searched
PubMed, Web of Science and EbscoHost databases for all published articles from
January 2000 to March 2014 that presented estimates of transitions in US youth
and adult study populations over time between at least one of the following
tobacco use states: exclusive cigarette smoking, exclusive smokeless tobacco use,
dual use of both products, and use of neither product. We excluded non-English
language studies, studies published before 2000, clinical trials, controlled
cessation programs, and clinical studies or evaluations of smokeless tobacco
cessation programs. RESULTS: The review identified six studies on US populations
published since 2000 with longitudinal data on some or all of the transitions
that users can undergo between smokeless tobacco and cigarette use. There was
considerable heterogeneity across studies in design and tobacco use definitions.
Despite these differences, the existing data indicate that switching behaviors
from exclusive smoking to exclusive smokeless tobacco use are limited (adults: 0%
1.4%, adolescents: 0.8%-3.8%) but may be more common from exclusive smokeless
tobacco use to exclusive smoking (adults: 0.9%-26.6%, adolescents: 16.6%-25.5%).
Among adults, exclusive cigarette smoking was generally stable and consistent
(79.7% to 87.6%) over follow-up across studies but less stable in adolescents
(46.8%-78.7%). Exclusive smokeless tobacco use was less stable than exclusive
cigarette smoking over time (adults: 59.4%-76.6%, adolescents: 26.2%-44.8%).
CONCLUSION: This review provides published estimates of the proportions of adults
and adolescents transitioning between tobacco use categories from the most
recently available studies on longitudinal transitions between smokeless tobacco
and cigarettes in the US. These data can be used to track tobacco use behaviors
and evaluate their effect on public health; however, the data for these studies
were generally collected more than a decade ago. Additional research including
nationally representative longitudinal estimates using consistent definitions and
designs, would improve understanding of current tobacco transition behaviors.
PMID- 25849606
TI - Functional characterization of putative novel splicing mutations in the
cardiomyopathy-causing genes.
AB - Molecular diagnosis of cardiomyopathies remains difficult not only because of the
large number of causative genes and the high rate of private mutations but also
due to the large number of unclassified variants (UVs) found in patients' DNA.
This study reports the functional splicing impact of nine novel genomic
variations previously identified in unrelated patients with cardiomyopathies. To
identify splice variants among these UVs, a combination of in silico and in vitro
hybrid minigene tools was used as transcript is not available. Using this two
step approach, these UVs were reclassified as splicing mutations (MYBPC3-c.655
25A>G, MYBPC3-c.1790G>A (p.Arg597Gln), MYBPC3-c.2414-36G>T) or as mutations with
a majority of abnormally spliced transcripts (MYBPC3-c.1182C>A, TNNT2-c.460G>A
(p.Glu154Lys), and TNNT2-c.822-3C>A) or as variations with a weak splicing effect
(TNNT2-c.1000-38C>A). For the two remaining variations in intron 11 of the TNNT2
gene in the vicinity of the acceptor splice site (c.571-7G>A, c.571-29G>A), a
minigene assay was inconclusive as exon 12 is neither recognized as an exon by
HeLa nor by H9c2 cells. Our study highlights the importance of the combined use
of in silico and in vitro splicing assays to improve the prediction of the
functional splicing impact of identified genetic variants if the RNA sample from
the patient is not easily available.
PMID- 25849605
TI - Radiological and pathological features associated with IDH1-R132H mutation status
and early mortality in newly diagnosed anaplastic astrocytic tumours.
AB - BACKGROUND: Glioblastoma can occur either de novo or by the transformation of a
low grade tumour; the majority of which harbor a mutation in isocitrate
dehydrogenase (IDH1). Anaplastic tumours are high-grade gliomas that may
represent the final step in the evolution of a secondary glioblastoma or the
initial presentation of an early primary glioblastoma. We sought to determine
whether pathological and/or radiological variables exist that can reliably
distinguish IDH1-R132H-positive from IDH1-R132H-negative tumours and to identify
variables associated with early mortality. METHODS: Patients diagnosed with
anaplastic astrocytic tumours were included. Magnetic resonance imaging was
performed and immunohistochemistry was used to identify tumours with the IDH1
R132H mutation. Survival was assessed 12 months after diagnosis. Variables
associated with IDH1-R132H status were identified by univariate and ROC analysis.
RESULTS: 37 gliomas were studied; 18 were positive for the IDH1-R132H mutation.
No tumours demonstrated a combined loss of chromosomes 1p/19q. Patients with IDH1
R132H-positive tumours were less likely to die within 12 months of diagnosis (17%
vs. 47%; p=0.046), more likely to have tumours located in the frontal lobe (55%
vs. 16%; p=0.015), and have a higher minimum apparent diffusion coefficient
(1.115 x 10-3 mm2/sec vs. 0.838 x 10-3 mm2/sec; p=0.016), however, these
variables demonstrated only moderate strength for predicting the IDH1-R132H
mutation status (AUC=0.735 and 0.711, respectively). The Ki-67 index was
significantly lower in IDH1-R132H-positive tumours (0.13 vs. 0.21; p=0.034). An
increased risk of death was associated with contrast-enhancement >= 5 cm3 in
patients with IDH1-R132H-positive tumours while edema >= 1 cm beyond the tumour
margin and < 5 mitoses/mm2 were associated with an increased risk of death in
patients with IDH1-R132H-negative tumours. CONCLUSIONS: IDH1-R132H-positive and
negative anaplastic tumours demonstrate unique features. Factors associated with
early mortality are also dependent on IDH1-R132H status and can be used to
identify patients at high risk for death.
PMID- 25849607
TI - Change in and long-term investigation of neuro-otologic disorders in disaster
stricken Fukushima prefecture: retrospective cohort study before and after the
Great East Japan Earthquake.
AB - On March 11, 2011, Japan's northeast Pacific coast was hit by a gigantic
earthquake and subsequent tsunami. Soma City in Fukushima Prefecture is situated
approximately 44 km north of Fukushima Daiichi Nuclear Power Plant. Soma General
Hospital is the only hospital in Soma City that provides full-time
otolaryngological medical care. We investigated the changes in new patients from
one year before to three years after the disaster. We investigated 18,167 new
patients treated at our department during the four years from April 1, 2010 to
March 31, 2014. Of the new patients, we categorized the diagnoses into Meniere's
disease, acute low-tone sensorineural hearing loss, vertigo, sudden deafness,
tinnitus, and facial palsy as neuro-otologic symptoms. We also investigated the
changes in the numbers of patients whom we examined at that time concerning other
otolaryngological disorders, including epistaxis, infectious diseases of the
laryngopharynx, and allergic rhinitis. The total number of new patients did not
change remarkably on a year-to-year basis. Conversely, cases of vertigo,
Meniere's disease, and acute low-tone sensorineural hearing loss increased in
number immediately after the disaster, reaching a plateau in the second year and
slightly decreasing in the third year. Specifically, 4.8% of patients suffering
from these neuro-otologic diseases had complications from depression and other
mental diseases. With regard to new patients in our department, there was no
apparent increase in the number of patients suffering from diseases other than
neuro-otologic diseases, including epistaxis, and allergic rhinitis. Patients
suffering from vertigo and/or dizziness increased during the first few years
after the disaster. These results are attributed to the continuing stress and
tension of the inhabitants. This investigation of those living in the disaster
area highlights the need for long-term support.
PMID- 25849608
TI - Metal ion-directed dynamic splicing of DNA through global conformational change
by intramolecular complexation.
AB - Chemically engineered DNAs-in which global conformation can be modulated in
response to specific stimuli-could be allosteric functional DNAs themselves or
work as a modulator of the functional nucleic acids such as DNAzymes and
aptamers. Here, we show that two terpyridines built in the DNA backbone form a
stable intramolecular 1:2 complex, [M(terpy)2](2+), with divalent transition
metal ions. Upon complexation, the DNA conjugates adopt a Omega-shape structure,
in which two distal sequences located outside the terpyridines connect with each
other to form a continuous segment with a specific structure or sequence. Such a
DNA structure is globally controlled by local metal complexation events that can
be rationally designed based on general coordination chemistry. This method is
regarded as metal ion-directed dynamic sequence edition or DNA splicing. DNAzymes
with peroxidase-like activity can thus be regulated by several transition metal
ions through sequence edition techniques based on the Omega-motif.
PMID- 25849609
TI - Camellia sinensis in asymptomatic hyperuricemia: A meta-analysis of tea or tea
extract effects on uric acid levels.
AB - Flavanols of Camellia sinensis exhibit uric acid (UA) lowering effect, through
the modulation of both xanthine oxidase and urate excretion. In order to
investigate the potential benefit of Camellia Sinenis products in asymptomatic
hyperuricemia, a meta-analysis of long-term Randomized Controlled Trials (RCT)
with tea or tea extract has been conducted. From 20 human intervention studies
selected only 5 RCT (13 interventions) were suitable for meta-analysis (n = 472).
The current "normal" range set for hyperuricemia fails to identify patients with
potential metabolic disorders. Therefore on the basis of the literature data, we
fixed cut-off limits for UA baseline levels of 4.5 mg/dl for women, 6.1 mg/dl for
men, and 5.5 mg/dl for studies involving mixed populations. Statistically
significant effects were not found, but subgroup analysis revealed that the
Pooled Estimate effect was different in subjects with baseline levels under [MD
(95% CI): 0.1078 (-0.0528 to 0.2684)] and over the cut-off [MD (95% CI): -0.0239
(0.3311 to 0.2833)]. However, due to the low number of RCT and to the lack of
data on bioavailability, it is difficult to draw any firm conclusion and more
studies are needed to establish if tea flavanols could be useful in asymptomatic
hyperuricemia treatment.
PMID- 25849610
TI - Planar Mn4O cluster homochiral metal-organic framework for HPLC separation of
pharmaceutically important (+/-)-ibuprofen racemate.
AB - A planar tetracoordinated oxygen containing a homochiral metal-organic framework
(MOF) has been synthesized and characterized that can be used as a new chiral
stationary phase in high-performance liquid chromatography to efficiently
separate racemates such as pharmaceutically important (+/-)-ibuprofen and (+/-)-1
phenyl-1,2-ethanediol.
PMID- 25849611
TI - Typhoid fever in young children in Bangladesh: clinical findings, antibiotic
susceptibility pattern and immune responses.
AB - BACKGROUND: Children bear a large burden of typhoid fever caused by Salmonella
enterica serotype Typhi (S. Typhi) in endemic areas. However, immune responses
and clinical findings in children are not well defined. Here, we describe
clinical and immunological characteristics of young children with S. Typhi
bacteremia, and antimicrobial susceptibility patterns of isolated strains.
METHODS: As a marker of recent infection, we have previously characterized
antibody-in-lymphocyte secretion (TPTest) during acute typhoid fever in adults.
We similarly assessed membrane preparation (MP) IgA responses in young children
at clinical presentation, and then 7-10 days and 21-28 days later. We also
assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to
MP at these time points. We compared responses in young children (1-5 years) with
those seen in older children (6-17 years), adults (18-59 years), and age-matched
healthy controls. PRINCIPAL FINDINGS: We found that, compared to age-matched
controls patients in all age cohorts had significantly more MP-IgA responses in
lymphocyte secretion at clinical presentation, and the values fell in all groups
by late convalescence. Similarly, plasma IgA responses in patients were elevated
at presentation compared to controls, with acute and convalescent IgA and IgG
responses being highest in adults. T cell proliferative responses increased in
all age cohorts by late convalescence. Clinical characteristics were similar in
all age cohorts, although younger children were more likely to present with loss
of appetite, less likely to complain of headache compared to older cohorts, and
adults were more likely to have ingested antibiotics. Multi-drug resistant
strains were present in approximately 15% of each age cohort, and 97% strains had
resistance to nalidixic acid. CONCLUSIONS: This study demonstrates that S. Typhi
bacteremia is associated with comparable clinical courses, immunologic responses
in various age cohorts, including in young children, and that TPTest can be used
as marker of recent typhoid fever, even in young children.
PMID- 25849612
TI - Peroxynitrite decomposition catalyst prevents matrix metalloproteinase-9
activation and neurovascular injury after hemoglobin injection into the caudate
nucleus of rats.
AB - Hemoglobin (Hb) is a major constituent of blood and a potent mediator of
oxidative or nitrative stress after intracerebral hemorrhage (ICH). Our previous
study demonstrated that Hb could induce abundant peroxynitrite (ONOO(-))
formation in vivo, which may be involved in the blood-brain barrier (BBB)
disruption, however, the drug intervention is absent and also the underlying
mechanism. Using an experimental stroke model by injecting Hb into the caudate
nucleus of male Sprague-Dawley rats, we assessed the role of ONOO(-)
decomposition catalyst, 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato
iron(III) [FeTPPS] in the activation of MMP-9 and Hb-induced neurovascular
injuries. 3-Nitrotyrosine (3-NT, as an index of ONOO(-) formation) and NF-kappaB
expression was measured by western blot (WB) and immunohistochemistry
(IHC)/immunofluorescence (IF). Activity of MMP was evaluated by in situ
zymography. Neurovascular injury was assessed using zonula occludens-1 (ZO-1) by
WB and IF, fibronectin (FN) and neuron-specific nuclear protein (NeuN) IHC.
Perihematomal cell death was determined by TUNEL assay. Behavioral outcome was
measured by modified neurological severity score (mNSS) test. At the injured
striata, profuse 3-NT was produced and mainly expressed in neutrophils and
microglia/macrophages. 3-NT formation significantly colocalized with nuclear
factor-kappaB (NF-kappaB) expression. In situ zymography showed that gelatinase
activity was mostly co-localized with neurons and blood vessel walls and partly
with neutrophils and microglia/macrophages. Enhanced 3-NT production, NF-kappaB
induction and MMP-9 activation were obviously reduced after FeTPPS treatment. Hb
induced injury to tight junction protein (ZO-1), basal lamina of FN
immunopositive microvasculature and neural cells was evidently ameliorated by
FeTPPS. In addition, apoptotic cell numbers as well as behavioral deficits were
also improved. The present study shows that the administration of the ONOO(-)
decomposition catalyst FeTPPS protects against Hb-induced neurovascular injuries
and improves neurological function, which possibly in part by suppressing MMP-9
activation.
PMID- 25849613
TI - Effect of mental fatigue on speed-accuracy trade-off.
AB - The aim of this study was to investigate the effects of mental fatigue on the
duration of actual and imagined goal-directed arm movements involving speed
accuracy trade-off. Ten participants performed actual and imagined point-to-point
arm movements as accurately and as fast as possible, before and after a 90-min
sustained cognitive task inducing mental fatigue, and before and after viewing a
neutral control task (documentary movie) that did not induce mental fatigue.
Target width and center-to-center target distance were varied, resulting in five
different indexes of difficulty. Prior to mental fatigue, actual and imagined
movement duration increased with the difficulty of the task, as predicted by
Fitts' law. Mental fatigue task induced a 4.1+/-0.7% increase in actual movement
duration and a 9.6+/-1.1% increase in imagined movement duration, independently
of the index of difficulty. The trial-by-trial evolution of actual and imagined
movement duration remained stable with mental fatigue. The control task did not
induce any change in actual and imagined movement duration. The results suggested
that movement was slowed in the presence of mental fatigue, maybe due to
proactive changes occurring during the preparatory state of the movement, to
preserve task success.
PMID- 25849614
TI - Neurochemical and electrophysiological deficits in the ventral hippocampus and
selective behavioral alterations caused by high-fat diet in female C57BL/6 mice.
AB - Mounting experimental evidence, predominantly from male rodents, demonstrates
that high-fat diet (HFD) consumption and ensuing obesity are detrimental to the
brain. To shed additional light on the neurological consequences of HFD
consumption in female rodents and to determine the relatively early impact of HFD
in the likely continuum of neurological dysfunction in the context of chronic HFD
intake, this study investigated effects of HFD feeding for up to 12weeks on
selected behavioral, neurochemical, and electrophysiological parameters in adult
female C57BL/6 mice; particular focus was placed on the ventral hippocampus
(vHIP). Selected locomotor, emotional and cognitive functions were evaluated
using behavioral tests after 5weeks on HFD or control (low-fat diet) diets. One
week later, mice were sacrificed and brain regional neurochemical (monoamine)
analysis was performed. Behaviorally naive mice were maintained on their
respective diets for an additional 5-6weeks at which time synaptic plasticity was
determined in ex vivo slices from the vHIP. HFD-fed female mice exhibited
increased: (i) locomotor activity in the open field testing, (ii) mean turn time
on the pole test, (iii) swimming time in the forced swim test, and (iv) number of
marbles buried in the marble burying test. In contrast, the novel object
recognition memory was unaffected. Mice on HFD also had decreased norepinephrine
and dopamine turnover, respectively, in the prefrontal cortex and the vHIP. HFD
consumption for a total of 11-12weeks altered vHIP synaptic plasticity, evidenced
by significant reductions in the paired-pulse ratio and long-term potentiation
(LTP) magnitude. In summary, in female mice, HFD intake for several weeks induced
multiple behavioral alterations of mainly anxiety-like nature and impaired
monoamine pathways in a brain region-specific manner, suggesting that in the
female, certain behavioral domains (anxiety) and associated brain regions, i.e.,
the vHIP, are preferentially targeted by HFD.
PMID- 25849616
TI - An ANNEXIN-like protein from the cereal cyst nematode Heterodera avenae
suppresses plant defense.
AB - Parasitism genes encoding secreted effector proteins of plant-parasitic nematodes
play important roles in facilitating parasitism. An annexin-like gene was
isolated from the cereal cyst nematode Heterodera avenae (termed Ha-annexin) and
had high similarity to annexin 2, which encodes a secreted protein of Globodera
pallida. Ha-annexin encodes a predicted 326 amino acid protein containing four
conserved annexin domains. Southern blotting revealed that there are at least two
homologies in the H. avenae genome. Ha-annexin transcripts were expressed within
the subventral gland cells of the pre-parasitic second-stage juveniles by in situ
hybridization. Additionally, expression of these transcripts were relatively
higher in the parasitic second-stage juveniles by quantitative real-time RT-PCR
analysis, coinciding with the time when feeding cell formation is initiated.
Knockdown of Ha-annexin by method of barley stripe mosaic virus-based host
induced gene silencing (BSMV-HIGS) caused impaired nematode infections at 7 dpi
and reduced females at 40 dpi, indicating important roles of the gene in
parasitism at least in early stage in vivo. Transiently expression of Ha-ANNEXIN
in onion epidermal cells and Nicotiana benthamiana leaf cells showed the whole
cell-localization. Using transient expression assays in N. benthamiana, we found
that Ha-ANNEXIN could suppress programmed cell death triggered by the pro
apoptotic mouse protein BAX and the induction of marker genes of PAMP-triggered
immunity (PTI) in N. benthamiana. In addition, Ha-ANNEXIN targeted a point in the
mitogen-activated protein kinase (MAPK) signaling pathway downstream of two
kinases MKK1 and NPK1 in N. benthamiana.
PMID- 25849615
TI - The role of TRPM2 in hydrogen peroxide-induced expression of inflammatory
cytokine and chemokine in rat trigeminal ganglia.
AB - Trigeminal ganglia (TG) contain neuronal cell bodies surrounded by satellite
glial cells. Although peripheral injury is well known to induce changes in gene
expression within sensory ganglia, detailed mechanisms whereby peripheral injury
leads to gene expression within sensory ganglia are not completely understood.
Reactive oxygen species (ROS) are an important modulator of hyperalgesia, but the
role of ROS generated within sensory ganglia is unclear. Since ROS are known to
affect transcription processes, ROS generated within sensory ganglia could
directly influence gene expression and induce cellular changes at the soma level.
In this study, we hypothesized that peripheral inflammation leads to cytokine and
chemokine production and ROS generation within TG and that transient receptor
potential melastatin (TRPM2), a well known oxidative sensor, contributes to ROS
induced gene regulation within TG. The masseter injection of complete Freund's
adjuvant (CFA) resulted in a significantly elevated level of ROS within TG of the
inflamed side with a concurrent increase in cytokine expression in TG. Treatment
of TG cultures with H2O2 significantly up-regulated mRNA and protein levels of
cytokine/chemokine such as interleukin 6 (IL-6) and chemokine (C-X-C motif)
ligand 2 (CXCL2). TRPM2 was expressed in both neurons and non-neuronal cells in
TG, and pretreatment of TG cultures with 2-aminoethoxydiphenyl borate (2-APB), an
inhibitor of TRPM2, or siRNA against TRPM2 attenuated H2O2-induced up-regulation
of IL-6 and CXCL2. These results suggested that activation of TRPM2 could play an
important role in the modulation of cytokine/chemokine expression within TG under
oxidative stress and that such changes may contribute to amplification of
nociceptive signals leading to pathological pain conditions.
PMID- 25849618
TI - Artificial miRNAs Targeting Mutant Huntingtin Show Preferential Silencing In
Vitro and In Vivo.
AB - Huntington's disease (HD) is a dominantly inherited neurodegenerative disease
caused by CAG repeat expansion in exon 1 of huntingtin (HTT). Studies in mouse
models of HD with a regulated mutant transgene show that continuous mutant allele
expression is required for behavioral and pathological signs; when mutant HTT
expression declined, neuronal degeneration improved. To date, it is unknown
whether neural cells in the adult human brain can tolerate reduction in both
normal and mutant alleles. Thus, it may be important to develop allele-specific
silencing approaches. Several siRNA sequences targeting the CAG expanded motif or
prevalent single-nucleotide polymorphisms (SNPs) in linkage disequilibrium with
the mutant allele have been designed and their selectivity demonstrated in vitro.
However, it is unknown whether these allele-specific siRNAs will retain their
specificity when expressed from artificial RNAi platforms. Here, we designed CAG-
and SNP- targeting artificial miRNAs and demonstrate that some, but not all,
retained their selectivity in vitro using an allele-specific reporter system and
in vivo in a transgenic mouse model developed to express normal and mutant human
HTT alleles.
PMID- 25849617
TI - Predictors of rational management of diarrhea in an endemic setting: observation
from India.
AB - BACKGROUND: Decades after the establishment of clear guidelines for management,
mostly due to irrational approach, diarrhea is still a major concern in the
developing world, including India. The scenario is even worse in urban slums
owing to poor health-seeking and socio-environmental vulnerability. Determining
the distribution of rational diarrhea management by practitioners and
identification of its important predictors seemed urgent to minimize the
potential for antibiotic resistance, diarrhea-related mortality and morbidity in
these areas. METHODS: Between May 2011 and January 2012, 264 consenting, randomly
selected qualified and non-qualified practitioners (including pharmacists) were
interviewed in the slums of Kolkata, a populous city in eastern India, regarding
their characteristics, diarrhea-related knowledge (overall and in six separate
domains: signs/symptoms, occurrence/spread, management, prevention/control,
cholera and ORS), prescribed antibiotics, intravenous fluid (IVF) and laboratory
investigations. Rationality was established based on standard textbooks. RESULTS:
Among participants, 53.03% had no medical qualifications, 6.06% were attached to
Governmental hospitals, 19.32% had best knowledge regarding diarrhea. While
treating diarrhea, 7.20%, 17.80% and 20.08% respectively advised antibiotics, IVF
and laboratory tests rationally. Logistic regression revealed that qualified and
Governmental-sector practitioners managed diarrhea more rationally. Having best
diarrhea-related knowledge regarding signs/symptoms (OR=5.49, p value=0.020),
occurrence/spread (OR=3.26, p value=0.035) and overall (OR=6.82, p value=0.006)
were associated with rational antibiotic prescription. Rational IVF
administration was associated with best knowledge regarding diarrheal
signs/symptoms (OR=3.00, p value=0.017), occurrence/spread (OR=3.57, p
value=0.004), prevention/control (OR=4.89, p value=0.037), ORS (OR=2.55, p
value=0.029) and overall (OR=4.57, p value<0.001). Best overall (OR=2.68, p
value=0.020) and cholera-related knowledge (OR=2.34, p value=0.019) were
associated with rational laboratory testing strategy. CONCLUSION: Diarrheal
management practices were unsatisfactory in urban slums where practitioners'
knowledge was a strong predictor for rational management. Interventions targeting
non-qualified, independent practitioners to improve their diarrhea-related
knowledge seemed to be required urgently to ensure efficient management of
diarrhea in these endemic settings.
PMID- 25849619
TI - Non-homogeneous fractal hierarchical weighted networks.
AB - A model of fractal hierarchical structures that share the property of non
homogeneous weighted networks is introduced. These networks can be completely and
analytically characterized in terms of the involved parameters, i.e., the size of
the original graph Nk and the non-homogeneous weight scaling factors r1, r2, . .
. rM. We also study the average weighted shortest path (AWSP), the average degree
and the average node strength, taking place on the non-homogeneous hierarchical
weighted networks. Moreover the AWSP is scrupulously calculated. We show that the
AWSP depends on the number of copies and the sum of all non-homogeneous weight
scaling factors in the infinite network order limit.
PMID- 25849620
TI - Elevational distribution and extinction risk in birds.
AB - Mountainous regions are hotspots of terrestrial biodiversity. Unlike islands,
which have been the focus of extensive research on extinction dynamics, fewer
studies have examined mountain ranges even though they face increasing threats
from human pressures - notably habitat conversion and climate change. Limits to
the taxonomic and geographical extent and resolution of previously available
information have precluded an explicit assessment of the relative role of
elevational distribution in determining extinction risk. We use a new global
species-level avian database to quantify the influence of elevational
distribution (range, maximum and midpoint) on extinction risk in birds at the
global scale. We also tested this relationship within biogeographic realms,
higher taxonomic levels, and across phylogenetic contrasts. Potential confounding
variables (i.e. phylogenetic, distributional, morphological, life history and
niche breadth) were also tested and controlled for. We show that the three
measures of elevational distribution are strong negative predictors of avian
extinction risk, with elevational range comparable and complementary to that of
geographical range size. Extinction risk was also found to be positively
associated with body weight, development and adult survival, but negatively
associated with reproduction and niche breadth. The robust and consistent
findings from this study demonstrate the importance of elevational distribution
as a key driver of variation in extinction dynamics in birds. Our results also
highlight elevational distribution as a missing criterion in current schemes for
quantifying extinction risk and setting species conservation priorities in birds.
Further research is recommended to test for generality across non-avian taxa,
which will require an advance in our knowledge of species' current elevational
ranges and increased efforts to digitise and centralise such data.
PMID- 25849621
TI - Dysregulation of microRNAs in breast cancer and their potential role as
prognostic and predictive biomarkers in patient management.
AB - MicroRNAs (miRNAs) are an emerging class of gene expression modulators with
relevant roles in several biological processes, including cell differentiation,
development, apoptosis, and regulation of the cell cycle. Deregulation of those
tiny RNA molecules has been described frequently as a major determinant for the
initiation and progression of diseases, including cancer. Not only miRNAs but
also the enzymes responsible for miRNA processing could be deregulated in cancer.
In this review, we address the role of miRNAs in the pathogenesis of breast
cancer, since there are oncogenic, tumor-suppressive, and metastatic-influencing
miRNAs. Additionally, the different detection platforms and normalization
strategies for miRNAs will be discussed. The major part of this review, however,
will focus on the capability of miRNAs to act as diagnostic, predictive, or
prognostic biomarkers. We will give an overview of their potential to correlate
with response to or benefit from a given treatment and we will consider their
ability to give information on prognosis in breast cancer. We will focus on
miRNAs validated by more than one study or verified in independent cohorts or
where results rely on preclinical as well as clinical evidence. As such, we will
discuss their potential use in the personalized management of breast cancer.
PMID- 25849622
TI - Regulation of IL-17A responses in human airway smooth muscle cells by Oncostatin
M.
AB - BACKGROUND: Regulation of human airway smooth muscle cells (HASMC) by cytokines
contributes to chemotactic factor levels and thus to inflammatory cell
accumulation in lung diseases. Cytokines such as the gp130 family member
Oncostatin M (OSM) can act synergistically with Th2 cytokines (IL-4 and IL-13) to
modulate lung cells, however whether IL-17A responses by HASMC can be altered is
not known. OBJECTIVE: To determine the effects of recombinant OSM, or other gp130
cytokines (LIF, IL-31, and IL-6) in regulating HASMC responses to IL-17A,
assessing MCP-1/CCL2 and IL-6 expression and cell signaling pathways. METHODS:
Cell responses of primary HASMC cultures were measured by the assessment of
protein levels in supernatants (ELISA) and mRNA levels (qRT-PCR) in cell
extracts. Activation of STAT, MAPK (p38) and Akt pathways were measured by
immunoblot. Pharmacological agents were used to assess the effects of inhibition
of these pathways. RESULTS: OSM but not LIF, IL-31 or IL-6 could induce
detectable responses in HASMC, elevating MCP-1/CCL2, IL-6 levels and activation
of STAT-1, 3, 5, p38 and Akt cell signaling pathways. OSM induced synergistic
action with IL-17A enhancing MCP-1/CCL-2 and IL-6 mRNA and protein expression,
but not eotaxin-1 expression, while OSM in combination with IL-4 or IL-13
synergistically induced eotaxin-1 and MCP-1/CCL2. OSM elevated steady state mRNA
levels of IL-4Ralpha, OSMRbeta and gp130, but not IL-17RA or IL-17RC.
Pharmacologic inhibition of STAT3 activation using Stattic down-regulated OSM,
OSM/IL-4 or OSM/IL-13, and OSM/IL-17A synergistic responses of MCP-1/CCL-2
induction, whereas, inhibitors of Akt and p38 MAPK resulted in less reduction in
MCP-1/CCL2 levels. IL-6 expression was more sensitive to inhibition of p38 (using
SB203580) and was affected by Stattic in response to IL-17A/OSM stimulation.
CONCLUSIONS: Oncostatin M can regulate HASMC responses alone or in synergy with
IL-17A. OSM/IL-17A combinations enhance MCP-1/CCL2 and IL-6 but not eotaxin-1.
Thus, OSM through STAT3 activation of HASMC may participate in inflammatory cell
recruitment in inflammatory airway disease.
PMID- 25849624
TI - Correction: bony healing of unstable thoracolumbar burst fractures in the elderly
using percutaneously applied titanium mesh cages and a transpedicular fixation
system with expandable screws.
PMID- 25849623
TI - Social functioning trajectories of young first-episode psychosis patients with
and without cannabis misuse: a 30-month follow-up study.
AB - The aim of the study was to investigate trajectories of social functioning in
young people with first-episode psychosis (FEP) with and without cannabis misuse
using a secondary analysis of data from the Episode-II trial. Forty-two young
people with FEP and comorbid cannabis use disorder were compared with 39 young
people with FEP but without a cannabis use disorder. Social functioning was
assessed every 6 months during a 30-month follow-up. Multilevel linear growth
curve modeling was used to compare the social functioning trajectories over time
for those with and without cannabis misuse. Cannabis misuse was not associated
with social functioning at baseline assessment. Over a 30-month follow-up, FEP
patients without cannabis disorder showed significant improvements in their
social functioning, whereas patients with cannabis misuse at baseline displayed
no such improvement. Patients with and without cannabis misuse differed
significantly in their levels of social functioning after 24 months. Similar
results were obtained after adjusting for potential confounders (i.e., age,
gender, negative symptoms, premorbid functioning, DSM-IV diagnoses, baseline
social functioning and other substance use). In the context of a specialized
early intervention service, patients with cannabis misuse at baseline did not
attain the improvements in social outcomes observed in their counterparts without
cannabis misuse. There is a need to develop effective interventions to reduce
cannabis misuse to ultimately improve social outcomes in young people with
psychosis.
PMID- 25849625
TI - Pilot Study on the Effect of Botanical Medicine (Tribulus terrestris) on Serum
Testosterone Level and Erectile Function in Aging Males With Partial Androgen
Deficiency (PADAM).
AB - This study was conducted on 30 consecutive male patients presenting to Kasr-Al
Ainy Andrology outpatient clinic complaining of manifestations of partial
androgen deficiency in aging males (PADAM). In this study (750 mg/day) of
Tribulus terrestris in 3 divided doses, each of 250 mg, as an endogenous
testosterone enhancer had been tried for a duration of 3 months and the
evaluation of its effect had been monitored for each patient concerning its
effect on serum testosterone (total and free) and luteinizing hormone (LH), as
well as its impact on erectile function, which was evaluated by the International
Index of Erectile Function-5 (IIEF-5) questionnaire for those patients. Results
showed a statistically significant difference in the level of testosterone (total
and free) and IIEF-5, but no statistically significant difference in the level of
LH before and after treatment. Also, the study showed statistically significant
correlation between testosterone (total and free) and IIEF-5, but no
statistically significant correlation between the level of LH and the IIEF-5
before and after treatment.
PMID- 25849626
TI - Poly(amidoamine) Dendrimers with Carbonic Anhydrase Inhibitory Activity and
Antiglaucoma Action.
AB - Four generations of poly(amidoamine) (PAMAM) dendrimers decorated with
benzenesulfonamide moieties were prepared by derivatizing the amino groups of the
dendrimer with 4-carboxy-benzenesulfonamide functionalities. Compounds
incorporating 4, 8, 16, and 32 sulfonamide moieties were thus obtained, which
showed an increasing carbonic anhydrase (CA, EC 4.2.1.1) inhibitory action with
the increase of the number of sulfamoyl groups in the dendrimer. Best inhibitory
activity (in the low nanomolar-subnanomolar range) was observed for isoforms CA
II and XII, involved among others in glaucoma. In an animal model of this
disease, the chronic administration of such dendrimers for 5 days led to a much
more efficient drop of intraocular pressure compared to the standard drug
dorzolamide.
PMID- 25849627
TI - A randomized trial comparing the diagnostic accuracy of visual inspection with
acetic acid to Visual Inspection with Lugol's Iodine for cervical cancer
screening in HIV-infected women.
AB - Visual inspection with Acetic Acid (VIA) and Visual Inspection with Lugol's
Iodine (VILI) are increasingly recommended in various cervical cancer screening
protocols in low-resource settings. Although VIA is more widely used, VILI has
been advocated as an easier and more specific screening test. VILI has not been
well-validated as a stand-alone screening test, compared to VIA or validated for
use in HIV-infected women. We carried out a randomized clinical trial to compare
the diagnostic accuracy of VIA and VILI among HIV-infected women. Women attending
the Family AIDS Care and Education Services (FACES) clinic in western Kenya were
enrolled and randomized to undergo either VIA or VILI with colposcopy. Lesions
suspicious for cervical intraepithelial neoplasia 2 or greater (CIN2+) were
biopsied. Between October 2011 and June 2012, 654 were randomized to undergo VIA
or VILI. The test positivity rates were 26.2% for VIA and 30.6% for VILI (p =
0.22). The rate of detection of CIN2+ was 7.7% in the VIA arm and 11.5% in the
VILI arm (p = 0.10). There was no significant difference in the diagnostic
performance of VIA and VILI for the detection of CIN2+. Sensitivity and
specificity were 84.0% and 78.6%, respectively, for VIA and 84.2% and 76.4% for
VILI. The positive and negative predictive values were 24.7% and 98.3% for VIA,
and 31.7% and 97.4% for VILI. Among women with CD4+ count < 350, VILI had a
significantly decreased specificity (66.2%) compared to VIA in the same group
(83.9%, p = 0.02) and compared to VILI performed among women with CD4+ count >=
350 (79.7%, p = 0.02). VIA and VILI had similar diagnostic accuracy and rates of
CIN2+ detection among HIV-infected women.
PMID- 25849628
TI - A humanized leucine zipper-TRAIL hybrid induces apoptosis of tumors both in vitro
and in vivo.
AB - Evidence suggests that stimulating apoptosis in malignant cells without
inflicting collateral damage to the host's normal tissues is a promising cancer
therapy. Chemo- and radiation therapies that, especially if combined, induce
apoptosis in tumor cells have been used for treating cancer patients for decades.
These treatments, however, are limited in their ability to discriminate between
malignant and non-malignant cells and, therefore, produce substantial healthy
tissue damage and subsequent toxic side-effects. In addition, as a result of
these therapies, many tumor types acquire an apoptosis-resistant phenotype and
become more aggressive and metastatic. Tumor necrosis factor-Related Apoptosis
Inducing Ligand (TRAIL) has been considered a promising and reliable selective
inducer of apoptosis in cancerous cells. TRAIL, however, is not uniformly
effective in cancer and multiple cancer cell types are considered resistant to
natural TRAIL. To overcome this deficiency of TRAIL, we have earlier constructed
a yeast-human hybrid leucine zipper-TRAIL in which the yeast GCN4-pII leucine
zipper was fused to human TRAIL (GCN4-TRAIL). This construct exhibited a
significantly improved anti-tumor apoptotic activity and safety, but is
potentially immunogenic in humans. Here, we report a novel, potent, and fully
human ATF7 leucine zipper-TRAIL (ATF7-TRAIL) fusion construct that is expected to
have substantially lower immunogenicity. In solution, ATF7-TRAIL exists solely as
a trimer with a Tm of 80 degrees C and is active against cancer cells both in
vitro and in vivo, in a mouse tumor xenograft model. Our data suggest that our re
engineered TRAIL is a promising candidate for further evaluation as an antitumor
agent.
PMID- 25849629
TI - Comparison of caudal and pre-scrotal castration for management of perineal hernia
in dogs between 2004 and 2014.
AB - AIMS: To compare peri- and post-operative complications associated with caudal
scrotal castration (CSC) and perineal hernia repair with pre-scrotal castration
(PSC) in conjunction with another surgical procedure. METHODS: Medical records
were reviewed for 51 intact male dogs that were admitted to the Veterinary
Emergency and Surgical Center, Levittown, PA, and underwent a CSC and perineal
hernia repair using an internal obturator muscle flap (IOMF) between 2004 and
2014. Perioperative, and major and minor post-operative complications noted
within the 2 week follow up period were reported and compared to 91 intact male
dogs that underwent a PSC in conjunction with a second surgical procedure.
RESULTS: There were no recorded perioperative or major post-operative
complications in either group. There were 3/51 (6%) minor post-operative
complications in the CSC group compared to 6/91 (7%) in the PSC group. There were
2/51 (4%) and 4/91 (4%) cases that developed heat, erythema and swelling
associated with the incision site and 1/51 (2%) and 2/91 (2%) cases that
developed scrotal swelling in the CSC and PSC groups, respectively. Overall,
there was no difference in the prevalence of minor complications between the two
groups (p=0.86). CONCLUSIONS AND CLINICAL RELEVANCE: Caudal scrotal castration
was not associated with more perioperative or postoperative complications
relative to PSC. Utilising the CSC approach eliminates the need to aseptically
prepare and drape a second site when carrying out perineal hernia repair, as well
as the need for patient repositioning. Thus, we recommend that CSC be the
preferred surgical technique when performing orchiectomy in dogs concurrent with
perineal hernia repair.
PMID- 25849631
TI - Smarter than others? Conjectures in lowest unique bid auctions.
AB - Research concerning various types of auctions, such as English auctions, Dutch
auctions, highest-price sealed-bid auctions, and second-price sealed-bid
auctions, is always a topic of considerable interest in interdisciplinary fields.
The type of auction, known as a lowest unique bid auction (LUBA), has also
attracted significant attention. Various models have been proposed, but they
often fail to explain satisfactorily the real bid-distribution characteristics.
This paper discusses LUBA bid-distribution characteristics, including the
inverted-J shape and the exponential decrease in the upper region. The authors
note that this type of distribution, which initially increases and later
decreases, cannot be derived from the symmetric Nash equilibrium framework based
on perfect information that has previously been used. A novel optimization model
based on non-perfect information is presented. The kernel of this model is the
premise that agents make decisions to achieve maximum profit based on imaginary
information or assumptions regarding the behavior of others.
PMID- 25849630
TI - Spectroscopic Determination of Distinct Heme Ligands in Outer-Membrane Receptors
PhuR and HasR of Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa PAO1 encodes two outer membrane receptors, PhuR
(Pseudomonas heme uptake) and HasR (heme assimilation system). The HasR receptor
acquires heme through interaction with a secreted hemophore, HasAp. The non
hemophore-dependent PhuR is encoded along with proteins required for heme
translocation into the cytoplasm. Herein, we report the isolation and
characterization of the HasR and PhuR receptors. Absorption and MCD spectroscopy
confirmed that, similar to other Gram-negative OM receptors, HasR coordinates
heme through the conserved N-terminal plug His-221 and His-624 of the surface
exposed FRAP-loop. In contrast, PhuR showed distinct absorption and MCD spectra
consistent with coordination through a Tyr residue. Sequence alignment of PhuR
with all known Gram-negative OM heme receptors revealed a lack of a conserved His
within the FRAP loop but two Tyr residues at positions 519 and 529. Site-directed
mutagenesis and spectroscopic characterization confirmed Tyr-519 and the N
terminal plug His-124 provide the heme ligands in PhuR. We propose that PhuR and
HasR represent nonredundant heme receptors capable of sensing and accessing heme
across a wide range of physiological conditions on colonization and infection of
the host.
PMID- 25849632
TI - Aspirin resistance in the acute stages of acute ischemic stroke is associated
with the development of new ischemic lesions.
AB - BACKGROUND: Aspirin is a primary antiplatelet agent for the secondary prevention
of ischemic stroke. However, if aspirin fails to inhibit platelet function, as is
expected in acute ischemic stroke (AIS), it may increase the rate of early
clinical events. Therefore, we sought to determine whether aspirin resistance in
the acute stage was associated with early radiological events, including new
ischemic lesions (NILs). METHODS: This study was a single-center, prospective,
observational study conducted between April 2012 and May 2013. Aspirin 300 mg was
initially administered followed by maintenance doses of 100 mg daily. The acute
aspirin reaction unit (aARU) was consistently measured after 3 hours of aspirin
loading. An aARU value >=550 IU was defined as biological aspirin resistance
(BAR). NILs on follow-up diffusion-weighted imaging (DWI) were defined as lesions
separate from index lesions, which were not detected on the initial DWI. RESULTS:
A total of 367 patients were analyzed in this study. BAR in aARU was detected in
60 patients (16.3%). On follow-up DWI, 81 patients (22.1%) had NILs, which were
frequently in the same territory as the index lesions (79%), pial infarcts
(61.7%), and located within the cortex (59.3%). BAR was independently associated
with NILs on follow-up DWI (adjusted OR 2.00, 95% CIs 1.01-3.96; p = 0.047).
CONCLUSION: In conclusion, BAR in aARU could be associated with NILs on follow-up
DWI in AIS. Therefore, a further prospective study with a longer follow-up period
is necessary to evaluate the clinical implications of aARU in AIS.
PMID- 25849633
TI - Expression and characterization of protein disulfide isomerase family proteins in
bread wheat.
AB - BACKGROUND: The major wheat seed proteins are storage proteins that are
synthesized in the rough endoplasmic reticulum (ER) of starchy endosperm cells.
Many of these proteins have intra- and intermolecular disulfide bonds. In
eukaryotes, the formation of most intramolecular disulfide bonds in the ER is
thought to be catalyzed by protein disulfide isomerase (PDI) family proteins. The
cDNAs that encode eight groups of bread wheat (Triticum aestivum L.) PDI family
proteins have been cloned, and their expression levels in developing wheat grains
have been determined. The purpose of the present study was to characterize the
enzymatic properties of the wheat PDI family proteins and clarify their
expression patterns in wheat caryopses. RESULTS: PDI family cDNAs, which are
categorized into group I (TaPDIL1Aalpha, TaPDIL1Abeta, TaPDIL1Agamma,
TaPDIL1Adelta, and TaPDIL1B), group II (TaPDIL2), group III (TaPDIL3A), group IV
(TaPDIL4D), and group V (TaPDIL5A), were cloned. The expression levels of
recombinant TaPDIL1Aalpha, TaPDIL1B, TaPDIL2, TaPDIL3A, TaPDIL4D, and TaPDIL5A in
Escherichia coli were established from the cloned cDNAs. All recombinant proteins
were expressed in soluble forms and purified. Aside from TaPDIL3A, the
recombinant proteins exhibited oxidative refolding activity on reduced and
denatured ribonuclease A. Five groups of PDI family proteins were distributed
throughout wheat caryopses, and expression levels of these proteins were higher
during grain filling than in the late stage of maturing. Localization of these
proteins in the ER was confirmed by fluorescent immunostaining of the immature
caryopses. In mature grains, the five groups of PDI family proteins remained in
the aleurone cells and the protein matrix of the starchy endosperm. CONCLUSIONS:
High expression of PDI family proteins during grain filling in the starchy
endosperm suggest that these proteins play an important role in forming
intramolecular disulfide bonds in seed storage proteins. In addition, these PDI
family proteins that remain in the aleurone layers of mature grains likely assist
in folding newly synthesized hydrolytic enzymes during germination.
PMID- 25849634
TI - Oep23 forms an ion channel in the chloroplast outer envelope.
AB - BACKGROUND: Metabolite, ion and protein translocation into chloroplasts occurs
across two membranes, the inner and the outer envelope. Solute and metabolite
channels fulfill very important functions in integrating the organelles into the
metabolic network of the cell. However so far only a few have been identified.
Here we describe the identification and the characterization of the outer
envelope protein of 23 kDa, Oep23 from garden pea. RESULTS: Oep23 is found in the
entire plant lineage from green algae to flowering plants. It is expressed in all
organs and developmental states tested so far. The reconstituted recombinant
protein Oep23 from pea forms a high conductance ion channel with a maximal
conductance in the fully open state of 466 +/- 14pS at a holding potential of
+100 mV (in 250 mM KCl). The Oep23 channel is cation selective (PK+ : PCl- = 15 :
1) with a voltage dependent open probability of maximal Vmem = 0 mV. CONCLUSION:
The data indicate that the Oep23 activity represents a single channel unit and
does not assemble into a multiple pore complex like bacterial type porins or
mitochondrial voltage dependent anion channel. Thus, Oep23 represents a new
member of ion channels in the outer envelope of chloroplasts involved in solute
exchange.
PMID- 25849635
TI - Quantifying cellular capacity identifies gene expression designs with reduced
burden.
AB - Heterologous gene expression can be a significant burden for cells. Here we
describe an in vivo monitor that tracks changes in the capacity of Escherichia
coli in real time and can be used to assay the burden imposed by synthetic
constructs and their parts. We identify construct designs with reduced burden
that predictably outperformed less efficient designs, despite having equivalent
output.
PMID- 25849636
TI - Massively parallel delivery of large cargo into mammalian cells with light
pulses.
AB - We report a high-throughput platform for delivering large cargo elements into
100,000 cells in 1 min. Our biophotonic laser-assisted surgery tool (BLAST)
generates an array of microcavitation bubbles that explode in response to laser
pulsing, forming pores in adjacent cell membranes through which cargo is gently
driven by pressurized flow. The platform delivers large items including bacteria,
enzymes, antibodies and nanoparticles into diverse cell types with high
efficiency and cell viability. We used this platform to explore the intracellular
lifestyle of Francisella novicida and discovered that the iglC gene is
unexpectedly required for intracellular replication even after phagosome escape
into the cell cytosol.
PMID- 25849637
TI - Correlation Map, a goodness-of-fit test for one-dimensional X-ray scattering
spectra.
AB - Assessing similarity between data sets with the reduced chi(2) test requires the
estimation of experimental errors, which, if incorrect, may render statistical
comparisons invalid. We report a goodness-of-fit test, Correlation Map (CorMap),
for assessing differences between one-dimensional spectra independently of
explicit error estimates, using only data point correlations. Using small-angle X
ray scattering data, we demonstrate that CorMap maintains the power of the
reduced chi(2) test; moreover, CorMap is also applicable to other physical
experiments.
PMID- 25849638
TI - Sequencing small genomic targets with high efficiency and extreme accuracy.
AB - The detection of minority variants in mixed samples requires methods for
enrichment and accurate sequencing of small genomic intervals. We describe an
efficient approach based on sequential rounds of hybridization with biotinylated
oligonucleotides that enables more than 1-million-fold enrichment of genomic
regions of interest. In conjunction with error-correcting double-stranded
molecular tags, our approach enables the quantification of mutations in
individual DNA molecules.
PMID- 25849639
TI - The F-box protein MAX2 contributes to resistance to bacterial phytopathogens in
Arabidopsis thaliana.
AB - BACKGROUND: The Arabidopsis thaliana F-box protein MORE AXILLARY GROWTH2 (MAX2)
has previously been characterized for its role in plant development. MAX2 appears
essential for the perception of the newly characterized phytohormone
strigolactone, a negative regulator of polar auxin transport in Arabidopsis.
RESULTS: A reverse genetic screen for F-box protein mutants altered in their
stress responses identified MAX2 as a component of plant defense. Here we show
that MAX2 contributes to plant resistance against pathogenic bacteria.
Interestingly, max2 mutant plants showed increased susceptibility to the
bacterial necrotroph Pectobacterium carotovorum as well as to the hemi-biotroph
Pseudomonas syringae but not to the fungal necrotroph Botrytis cinerea. max2
mutant phenotype was associated with constitutively increased stomatal
conductance and decreased tolerance to apoplastic ROS but also with alterations
in hormonal balance. CONCLUSIONS: Our results suggest that MAX2 previously
characterized for its role in regulation of polar auxin transport in Arabidopsis,
and thus plant development also significantly influences plant disease
resistance. We conclude that the increased susceptibility to P. syringae and P.
carotovorum is due to increased stomatal conductance in max2 mutants promoting
pathogen entry into the plant apoplast. Additional factors contributing to
pathogen susceptibility in max2 plants include decreased tolerance to pathogen
triggered apoplastic ROS and alterations in hormonal signaling.
PMID- 25849640
TI - Design and fabrication of magnetically functionalized flexible micropillar arrays
for rapid and controllable microfluidic mixing.
AB - Magnetically functionalized PDMS-based micropillar arrays have been successfully
designed, fabricated and implanted for controllable microfluidic mixing. The
arrangement of PDMS micropillar arrays inside the microchannel can be flexibly
controlled by an external magnetic field. As a consequence, the flow fields
inside the microchannel can be regulated at will via magnetic activation
conveniently. When a microchannel is implanted with such micropillar arrays, two
microstreams can be mixed easily and controllably upon the simple application of
an on/off magnetic signal. Mixing efficiencies based on micropillar arrays with
different densities were investigated and compared. It was found that micropillar
arrays with higher density (i.e. smaller pillar pitch) would render better mixing
performance. Our microfluidic system is capable of generating highly reproducible
results within many cycles of mixing/non-mixing conversion. We believe that the
simple mixing-triggering method together with rapid and controllable mixing
control will be extraordinarily valuable for various biological or chemical
applications in the future.
PMID- 25849641
TI - Research trends in evidence-based medicine: a joinpoint regression analysis of
more than 50 years of publication data.
AB - BACKGROUND: Evidence-based medicine (EBM) has developed as the dominant paradigm
of assessment of evidence that is used in clinical practice. Since its
development, EBM has been applied to integrate the best available research into
diagnosis and treatment with the purpose of improving patient care. In the EBM
era, a hierarchy of evidence has been proposed, including various types of
research methods, such as meta-analysis (MA), systematic review (SRV), randomized
controlled trial (RCT), case report (CR), practice guideline (PGL), and so on.
Although there are numerous studies examining the impact and importance of
specific cases of EBM in clinical practice, there is a lack of research
quantitatively measuring publication trends in the growth and development of EBM.
Therefore, a bibliometric analysis was constructed to determine the scientific
productivity of EBM research over decades. METHODS: NCBI PubMed database was used
to search, retrieve and classify publications according to research method and
year of publication. Joinpoint regression analysis was undertaken to analyze
trends in research productivity and the prevalence of individual research
methods. FINDINGS: Analysis indicates that MA and SRV, which are classified as
the highest ranking of evidence in the EBM, accounted for a relatively small but
auspicious number of publications. For most research methods, the annual percent
change (APC) indicates a consistent increase in publication frequency. MA, SRV
and RCT show the highest rate of publication growth in the past twenty years.
Only controlled clinical trials (CCT) shows a non-significant reduction in
publications over the past ten years. CONCLUSIONS: Higher quality research
methods, such as MA, SRV and RCT, are showing continuous publication growth,
which suggests an acknowledgement of the value of these methods. This study
provides the first quantitative assessment of research method publication trends
in EBM.
PMID- 25849642
TI - A novel, rapid method to quantify intraplatelet calcium dynamics by ratiometric
flow cytometry.
AB - Cytosolic free calcium ions represent important second-messengers in platelets.
Therefore, quantitative measurement of intraplatelet calcium provides a popular
and very sensitive tool to evaluate platelet activation and reactivity. Current
protocols for determination of intracellular calcium concentrations in platelets
have a number of limitations. Cuvette-based methods do not allow measurement of
calcium flux in complex systems, such as whole blood, and therefore require
isolation steps that potentially interfere with platelet activation. Flow
cytometry has the potential to overcome this limitation, but to date the
application of calibrated, quantitative readout of calcium kinetics has only been
described for Indo-1. As excitation of Indo-1 requires a laser in the ultraviolet
range, such measurements cannot be performed with a standard flow cytometer.
Here, we describe a novel, rapid calibration method for ratiometric calcium
measurement in platelets using both Ar(+)-laser excited fluorescence dyes Fluo-4
and Fura Red. We provide appropriate equations that allow rapid quantification of
intraplatelet calcium fluxes by measurement of only two standardisation buffers.
We demonstrate that this method allows quantitative calcium measurement in
platelet rich plasma as well as in whole blood. Further, we show that this method
prevents artefacts due to platelet aggregate formation and is therefore an ideal
tool to determine basal and agonist induced calcium kinetics.
PMID- 25849643
TI - Assessment of rival males through the use of multiple sensory cues in the
fruitfly Drosophila pseudoobscura.
AB - Environments vary stochastically, and animals need to behave in ways that best
fit the conditions in which they find themselves. The social environment is
particularly variable, and responding appropriately to it can be vital for an
animal's success. However, cues of social environment are not always reliable,
and animals may need to balance accuracy against the risk of failing to respond
if local conditions or interfering signals prevent them detecting a cue. Recent
work has shown that many male Drosophila fruit flies respond to the presence of
rival males, and that these responses increase their success in acquiring mates
and fathering offspring. In Drosophila melanogaster males detect rivals using
auditory, tactile and olfactory cues. However, males fail to respond to rivals if
any two of these senses are not functioning: a single cue is not enough to
produce a response. Here we examined cue use in the detection of rival males in a
distantly related Drosophila species, D. pseudoobscura, where auditory,
olfactory, tactile and visual cues were manipulated to assess the importance of
each sensory cue singly and in combination. In contrast to D. melanogaster, male
D. pseudoobscura require intact olfactory and tactile cues to respond to rivals.
Visual cues were not important for detecting rival D. pseudoobscura, while
results on auditory cues appeared puzzling. This difference in cue use in two
species in the same genus suggests that cue use is evolutionarily labile, and may
evolve in response to ecological or life history differences between species.
PMID- 25849647
TI - A novel microfluidic approach for extremely fast and efficient photochemical
transformations in fluoropolymer microcapillary films.
AB - The unique optical properties of the fluoropolymer microcapillary film (MCF)
material combined with the extremely fast photoinactivation of Herpes HSV-1
virus, and photodegradation of indigo carmine, diclofenac and benzoylecgonine in
the MCF array photoreactor, demonstrate a new, flexible and inexpensive platform
for rapid photochemical transformations, high-throughput process analytics and
photochemical synthesis.
PMID- 25849646
TI - Short-term dietary salt supplementation blunts telmisartan induced increases in
plasma renin activity in hypertensive patients with type 2 diabetes mellitus.
AB - Current guidelines recommend low dietary salt intake (LDS) in patients with
diabetes to reduce blood pressure (BP). However, low salt intake has been
associated with higher mortality rates in people with diabetes. Our aim is to
examine the effect of angiotensin II receptor blocker (ARB), telmisartan, with
and without dietary sodium chloride (NaCl) supplementation, on BP [mean arterial
pressure (MAP)], plasma renin activity (PRA), serum aldosterone level and
estimated glomerular filtration rate (eGFR) in hypertensive patients with type 2
diabetes. In a randomized, double-blind, placebo-controlled study (RCT), 28
patients with type 2 diabetes, treated with telmisartan (40 mg daily), received 2
weeks of placebo or NaCl capsules (100 mmol/24 h). Following a 6-week washout,
the protocol was repeated in reverse. Twenty-four-hour urinary sodium excretion
(24hUNa), ambulatory BP (ABP) monitoring and blood tests were performed before
and after each study phase. The telmisartan-associated increase in PRA was
blunted by approximately 50% during salt supplementation compared with placebo;
median PRA was 2.3 MUg/l/h with placebo compared with 1.7 MUg/l/h with salt
(P<0.001). A trend towards blunting of ARB induced increases in serum aldosterone
was also demonstrated. Salt supplementation significantly reduced the MAP
lowering effects of telmisartan (P<0.05). The present study demonstrates that
salt supplementation blunts the telmisartan induced increase in PRA in patients
with type 2 diabetes.
PMID- 25849644
TI - Signaling through IL-17C/IL-17RE is dispensable for immunity to systemic, oral
and cutaneous candidiasis.
AB - Candida albicans is a commensal fungal microbe of the human orogastrointestinal
tract and skin. C. albicans causes multiple forms of disease in immunocompromised
patients, including oral, vaginal, dermal and disseminated candidiasis. The
cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are
required for protection to most forms of candidiasis. The importance of the IL
17R pathway has been observed not only in knockout mouse models, but also in
humans with rare genetic mutations that impact generation of Th17 cells or the IL
17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or
IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct
subclass of cytokines with unique structural and signaling properties. IL-17A is
the best-characterized member of the IL-17 family to date, but far less is known
about other IL-17-related cytokines. In this study, we sought to determine the
role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and
disseminated forms of C. albicans infection. IL-17C signals through a
heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed
that IL-17C mRNA was induced following oral C. albicans infection. However, mice
lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin
and bloodstream at rates similar to WT littermate controls. Moreover, these mice
demonstrated similar gene transcription profiles and recovery kinetics as WT
animals. These findings indicate that IL-17C and IL-17RE are dispensable for
immunity to the forms of candidiasis evaluated, and illustrate a surprisingly
limited specificity of the IL-17 family of cytokines with respect to systemic,
oral and cutaneous Candida infections.
PMID- 25849645
TI - Decrease in plasma levels of alpha-synuclein is evident in patients with
Parkinson's disease after elimination of heterophilic antibody interference.
AB - There is substantial biochemical, pathological, and genetic evidence that alpha
synuclein (A-syn) is a principal molecule in the pathogenesis of Parkinson
disease (PD). We previously reported that total A-syn levels in cerebrospinal
fluid (CSF), measured with the specific enzyme-linked immunosorbent assay (ELISA)
developed by ourselves, were decreased in patients with PD, and suggested the
usefulness of A-syn in CSF and plasma as a biomarker for the diagnosis of PD.
After our report, a considerable number of studies have investigated the levels A
syn in CSF and in blood, but have reported inconclusive results. Such
discrepancies have often been attributed not only to the use of different
antibodies in the ELISAs but also to interference from hemolysis. In this study
we measured the levels of A-syn in CSF and plasma by using our own sandwich ELISA
with or without heterophilic antibody (HA) inhibitor in 30 patients with PD and
58 age-matched controls. We thereby revealed that HA interfered with ELISA
measurements of A-syn and are accordingly considered to be an important
confounder in A-syn ELISAs. HA produced falsely exaggerated signals in A-syn
ELISAs more prominently in plasma samples than in CSF samples. After elimination
of HA interference, it was found that hemolysis did not have a significant effect
on the signals obtained using our A-syn ELISA. Furthermore, plasma levels of A
syn were significantly lower in the PD group compared with the control group
following elimination of HA interference with an HA inhibitor. Our results
demonstrate that HA was a major confounder that should be controlled in A-syn
ELISAs, and that plasma A-syn could be a useful biomarker for the diagnosis of PD
if adequately quantified following elimination of HA interference.
PMID- 25849648
TI - Validity of a Trunk-Mounted Accelerometer to Measure Physical Collisions in
Contact Sports.
AB - CONTEXT: Accelerometer peak impact accelerations are being used to measure player
physical demands in contact sports. However, their accuracy to do so has not been
ascertained. PURPOSE: To compare peak-impact-acceleration data from an
accelerometer contained in a wearable tracking device with a 3-dimensional motion
analysis (MA) system during tackling and bumping. METHODS: Twenty-five semielite
rugby athletes wore a tracking device containing a 100-Hz triaxial accelerometer
(MinimaxX S4, Catapult Innovations, Australia). A single retroreflective marker
was attached to the device, with its position recorded by a 12-camera MA system
during 3 physical-collision tasks (tackle bag, bump pad, and tackle drill; N =
625). The accuracy, effect size, agreement, precision, and relative errors for
each comparison were obtained as measures of accelerometer validity. RESULTS:
Physical-collision peak impact accelerations recorded by the accelerometer
overestimated (mean bias 0.60 g) those recorded by the MA system (P < .01).
Filtering the raw data at a 20-Hz cutoff improved the accelerometer's
relationship with MA data (mean bias 0.01 g; P > .05). When considering the data
in 9 magnitude bands, the strongest relationship with the MA system was found in
the 3.0-g or less band, and the precision of the accelerometer tended to reduce
as the magnitude of impact acceleration increased. Of the 3 movements performed,
the tackle-bag task displayed the greatest validity with MA. CONCLUSIONS: The
findings indicate that the MinimaxX S4 accelerometer can accurately measure
physical-collision peak impact accelerations when data are filtered at a 20-Hz
cutoff frequency. As a result, accelerometers may be useful to measure physical
collisions in contact sports.
PMID- 25849649
TI - Vitamin D status and the risk for hospital-acquired infections in critically ill
adults: a prospective cohort study.
AB - INTRODUCTION: To identify patient characteristics associated with low serum 25
hydroxyvitamin D (25(OH)D) concentrations in the medical intensive care unit
(ICU) and examine the relationship between serum 25(OH)D and the risk for
hospital-acquired infections. METHODS: This is a prospective observational cohort
of adult patients admitted to the medical ICU at an urban safety net teaching
hospital in Atlanta, Georgia from November 1, 2011 through October 31, 2012 with
an anticipated ICU stay >= 1 day. Phlebotomy for serum 25(OH)D measurement was
performed on all patients within 5 days of ICU admission. Patients were followed
for 30 days or until death or hospital discharge, whichever came first. Hospital
acquired infections were determined using standardized criteria from review of
electronic medical record. RESULTS: Among the 314 patients analyzed, 178 (57%)
had a low vitamin D at a serum 25(OH)D concentration < 15 ng/mL. The patient
characteristics associated with low vitamin D included admission during winter
months (28% vs. 18%, P = 0.04), higher PaO2/FiO2 (275 vs. 226 torr, P = 0.03) and
a longer time from ICU admission to study phlebotomy (1.8 vs. 1.5 days, P =
0.02). A total of 36 (11%) patients were adjudicated as having a hospital
acquired infection and in multivariable analysis adjusting for gender, alcohol
use, APACHE II score, time to study phlebotomy, ICU length of stay and net fluid
balance, serum 25(OH)D levels < 15 ng/mL were not associated with risk for
hospital-acquired infections (HR 0.85, 95% CI 0.40-1.80, P = 0.7). CONCLUSIONS:
In this prospective, observational cohort of adults admitted to a single-center
medical ICU, we did not find a significant association between low 25(OH)D and
the risk for hospital-acquired infections.
PMID- 25849650
TI - Role of glucokinase in the subcellular localization of glucokinase regulatory
protein.
AB - Glucokinase (GCK) is the rate-limiting enzyme of liver glucose metabolism.
Through protein-protein interactions, glucokinase regulatory protein (GCKR) post
transcriptionally regulates GCK function in the liver, and causes its nuclear
localization. However the role of GCK in regulating GCKR localization is unknown.
In the present study, using in vitro and in vivo models, we examined the levels
of GCK and GCKR, and their subcellular localization. We found that total cellular
levels of GCKR did not vary in the in vivo models, but its subcellular
localization did. In animals with normal levels of GCK, GCKR is mainly localized
to the nuclei of hepatocytes. In seven-day old rats and liver-specific Gck gene
knockout mice (animals that lack or have reduced levels of GCK protein), GCKR was
found primarily in the cytoplasm. The interaction of GCK with GCKR was further
examined using in vitro models where we varied the levels of GCK and GCKR.
Varying the level of GCK protein had no effect on total cellular GCKR protein
levels. Taken together, our results indicate that GCK is important for the
localization of GCKR to the nucleus and raises the possibility that GCKR may have
functions in addition to those regulating GCK activity in the cytoplasm.
PMID- 25849651
TI - Identification of inhibitors of biological interactions involving intrinsically
disordered proteins.
AB - Protein-protein interactions involving disordered partners have unique features
and represent prominent targets in drug discovery processes. Intrinsically
Disordered Proteins (IDPs) are involved in cellular regulation, signaling and
control: they bind to multiple partners and these high-specificity/low-affinity
interactions play crucial roles in many human diseases. Disordered regions,
terminal tails and flexible linkers are particularly abundant in DNA-binding
proteins and play crucial roles in the affinity and specificity of DNA
recognizing processes. Protein complexes involving IDPs are short-lived and
typically involve short amino acid stretches bearing few "hot spots", thus the
identification of molecules able to modulate them can produce important lead
compounds: in this scenario peptides and/or peptidomimetics, deriving from
structure-based, combinatorial or protein dissection approaches, can play a key
role as hit compounds. Here, we propose a panoramic review of the structural
features of IDPs and how they regulate molecular recognition mechanisms focusing
attention on recently reported drug-design strategies in the field of IDPs.
PMID- 25849652
TI - The relevance of miRNA-21 in HSV-induced inflammation in a mouse model.
AB - The purpose of this study was to clarify the correlation between microRNA-21 (miR
21) expression and inflammation in a herpes simplex virus (HSV)-induced Behcet's
Disease (BD) mouse model. miR-21 was compared between BD patients and healthy
controls in peripheral blood mononuclear cells (PBMC). For miR-21 inhibition, miR
21 antagomir was applied to BD mice. The change of symptoms was monitored. The
levels of cytokines and related molecules were determined by ELISA and real time
qPCR. Treatment with colchicine or pentoxifylline down-regulated the level of miR
21 with improved symptoms in mice. miR-21 inhibition was accompanied by down
regulated serum levels of IL-17 and IL-6. The expression levels of PDCD4, RhoB,
PD-1, IL-12p35, and toll-like receptor-4 were also regulated by miR-21
inhibition. miR-21 was correlated with HSV-induced BD-like inflammation in mice
and BD patients. The expression of miR-21 was regulated by antagomir in mice.
PMID- 25849653
TI - Thermoresponsive interplay of water insoluble poly(2-alkyl-2-oxazoline)s
composition and supramolecular host-guest interactions.
AB - A series of water insoluble poly[(2-ethyl-2-oxazoline)-ran-(2-nonyl-2-oxazoline)]
amphiphilic copolymers was synthesized and their solubility properties in the
presence of different supramolecular host molecules were investigated. The
resulting polymer-cavitand assemblies exhibited a thermoresponsive behavior that
could be modulated by variation of the copolymer composition and length.
Interestingly, the large number of hydrophobic nonyl units across the polymer
chain induced the formation of kinetically-trapped nanoparticles in solution.
These nanoparticles further agglomerate into larger aggregates at a temperature
that is dependent on the polymer composition and the cavitand type and
concentration. The present research expands the understanding on the
supramolecular interactions between water insoluble copolymers and supramolecular
host molecules.
PMID- 25849654
TI - Analysis of bacterial and archaeal communities along a high-molecular-weight
polyacrylamide transportation pipeline system in an oil field.
AB - Viscosity loss of high-molecular-weight partially hydrolyzed polyacrylamide
(HPAM) solution was observed in a water injection pipeline before being injected
into subterranean oil wells. In order to investigate the possible involvement of
microorganisms in HPAM viscosity loss, both bacterial and archaeal community
compositions of four samples collected from different points of the
transportation pipeline were analyzed using PCR-amplification of the 16S rRNA
gene and clone library construction method together with the analysis of
physicochemical properties of HPAM solution and environmental factors. Further,
the relationship between environmental factors and HPAM properties with
microorganisms were delineated by canonical correspondence analysis (CCA).
Diverse bacterial and archaeal groups were detected in the four samples. The
microbial community of initial solution S1 gathered from the make-up tank is
similar to solution S2 gathered from the first filter, and that of solution S3
obtained between the first and the second filter is similar to that of solution
S4 obtained between the second filter and the injection well. Members of the
genus Acinetobacter sp. were detected with high abundance in S3 and S4 in which
HPAM viscosity was considerably reduced, suggesting that they likely played a
considerable role in HPAM viscosity loss. This study presents information on
microbial community diversity in the HPAM transportation pipeline and the
possible involvement of microorganisms in HPAM viscosity loss and biodegradation.
The results will help to understand the microbial community contribution made to
viscosity change and are beneficial for providing information for microbial
control in oil fields.
PMID- 25849655
TI - The neuronal-specific SGK1.1 (SGK1_v2) kinase as a transcriptional modulator of
BAG4, Brox, and PPP1CB genes expression.
AB - The Serum- and Glucocorticoid-induced Kinase 1, SGK1, exhibits a broad range of
cellular functions that include regulation of the number of ion channels in
plasma membrane and modulation of signaling pathways of cell survival. This
diversity of functions is made possible by various regulatory processes acting
upon the SGK1 gene, giving rise to various isoforms: SGK1_v1-5, each with
distinct properties and distinct aminotermini that serve to target proteins to
different subcellular compartments. Among cellular effects of SGK1 expression is
to indirectly modulate gene transcription by phosphorylating transcriptional
factors of the FOXO family. Here we examined if SGK1.1 (SGK1_v2; NM_001143676),
which associates primarily to the plasma membrane, is also able to regulate gene
expression. Using a differential gene expression approach we identified six genes
upregulated by SGK1.1 in HeLa cells. Further analysis of transcript and protein
levels validated two genes: BCL2-associated athanogene 4 (BAG-4) and Brox. The
results indicate that SGK1.1 regulates gene transcription upon a different set of
genes some of which participate in cell survival pathways (BAG-4) and others in
intracellular vesicular traffic (Brox).
PMID- 25849656
TI - SLM produced porous titanium implant improvements for enhanced vascularization
and osteoblast seeding.
AB - To improve well-known titanium implants, pores can be used for increasing bone
formation and close bone-implant interface. Selective Laser Melting (SLM) enables
the production of any geometry and was used for implant production with 250-um
pore size. The used pore size supports vessel ingrowth, as bone formation is
strongly dependent on fast vascularization. Additionally, proangiogenic factors
promote implant vascularization. To functionalize the titanium with proangiogenic
factors, polycaprolactone (PCL) coating can be used. The following proangiogenic
factors were examined: vascular endothelial growth factor (VEGF), high mobility
group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different
surfaces lead to different cell reactions, titanium and PCL coating were
compared. The growing into the porous titanium structure of primary osteoblasts
was examined by cross sections. Primary osteoblasts seeded on the different
surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells
had proliferated, but not migrated after seven days. Although the cell count was
lower on titanium PCL implants in LCI, the cell count and cell spreading area
development showed promising results for titanium PCL implants. HMGB1 showed the
highest migration capacity for stimulating the endothelial cell line. Future
perspective would be the incorporation of HMGB1 into PCL polymer for the
realization of a slow factor release.
PMID- 25849658
TI - A new series of kinked liquid crystals: 2-(6-alkoxynaphthalen-2-yl)-6
methoxyquinolines.
AB - A new series of 2-(6-alkoxynaphthalen-2-yl)-6-methoxyquinolines (nO-NpQOMe, n = 3
8) liquid crystal compounds, a linear molecular structure with two kinks, were
synthesized using a short two-step reaction with overall yields between 43% and
58%. Spectral analyses were in accord with the expected structures. Thermotropic
behavior of these liquid crystal compounds were investigated using polarized
optical microscopy and differential scanning calorimetry. All compounds exhibited
purely enantiotropic nematic phase at the medium-high temperature range of 162.4
234.2 degrees C. However, short ranges of nematic phase, 20.5-16.6 degrees C at
heating and 46.7-37.0 degrees C at cooling, were observed in these linear liquid
crystalline compounds with two kinks.
PMID- 25849657
TI - Impacts of gut bacteria on human health and diseases.
AB - Gut bacteria are an important component of the microbiota ecosystem in the human
gut, which is colonized by 1014 microbes, ten times more than the human cells.
Gut bacteria play an important role in human health, such as supplying essential
nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and
promoting angiogenesis and enteric nerve function. However, they can also be
potentially harmful due to the change of their composition when the gut ecosystem
undergoes abnormal changes in the light of the use of antibiotics, illness,
stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria
communities can cause many chronic diseases, such as inflammatory bowel disease,
obesity, cancer, and autism. This review summarizes and discusses the roles and
potential mechanisms of gut bacteria in human health and diseases.
PMID- 25849660
TI - Treat the brain and treat the periphery: toward a holistic approach to major
depressive disorder.
AB - The limited medication for major depressive disorder (MDD) against an ever-rising
disease burden presents an urgent need for therapeutic innovations. During recent
years, studies looking at the systems regulation of mental health and disease
have shown a remarkably powerful control of MDD by systemic signals. Meanwhile,
the identification of a host of targets outside the brain opens the way to treat
MDD by targeting systemic signals. We examine these emerging findings and
consider the implications for current thinking regarding MDD pathogenesis and
treatment. We highlight the opportunities and challenges of a periphery-targeting
strategy and propose its incorporation into a holistic approach.
PMID- 25849659
TI - Chromatin function modifying elements in an industrial antibody production
platform--comparison of UCOE, MAR, STAR and cHS4 elements.
AB - The isolation of stably transfected cell lines suitable for the manufacture of
biotherapeutic protein products can be an arduous process relying on the
identification of a high expressing clone; this frequently involves transgene
amplification and maintenance of the clones' expression over at least 60
generations. Maintenance of expression, or cell line stability, is highly
dependent upon the nature of the genomic environment at the site of transgene
integration, where epigenetic mechanisms lead to variable expression and
silencing in the vast majority of cases. We have assessed four chromatin function
modifying elements (A2UCOE, MAR X_S29, STAR40 and cHS4) for their ability to
negate chromatin insertion site position effects and their ability to express and
maintain monoclonal antibody expression. Each element was analysed by insertion
into different positions within a vector, either flanking or between heavy chain
(HC) and light chain (LC) antibody expression cassettes. Our results clearly show
that the A2UCOE is the most beneficial element in this system, with stable cell
pools and clones increasing antibody yields 6.5-fold and 6.75-fold respectively.
Stability analysis demonstrated that the reduction in antibody expression, seen
with cells transfected with the control vector over 120 generations, was
mitigated in the clones containing A2UCOE-augmented transgenes. Analysis also
showed that the A2UCOE reduced the amount of transgene promoter DNA methylation,
which contributed to the maintenance of starting levels of expression.
PMID- 25849661
TI - Palladium-catalyzed carbonylative Sonogashira coupling between aryl triazenes and
alkynes.
AB - We developed a palladium-catalyzed carbonylative Sonogashira reaction with aryl
triazenes and alkynes as substrates and methanesulfonic acid as the additive. A
series of alpha,beta-ynones were synthesized by this alternative procedure.
Notably, bromides, iodides and hydroxyl groups could be well-tolerated under
these reaction conditions.
PMID- 25849662
TI - Development and psychometric properties of an informant assessment scale of
theory of mind for adults with traumatic brain injury.
AB - Impairment of theory of mind (ToM) is a common phenomenon following traumatic
brain injury (TBI) that has clear effects on patients' social functioning. A
growing body of research has focused on this area, and several methods have been
developed to assess ToM deficiency. Although an informant assessment scale would
be useful for examining individuals with TBI, very few studies have adopted this
approach. The purpose of the present study was to develop an informant assessment
scale of ToM for adults with traumatic brain injury (IASToM-aTBI) and to test its
reliability and validity with 196 adults with TBI and 80 normal adults. A 44-item
scale was developed following a literature review, interviews with patient
informants, consultations with experts, item analysis, and exploratory factor
analysis (EFA). The following three common factors were extracted: social
interaction, understanding of beliefs, and understanding of emotions. The
psychometric analyses indicate that the scale has good internal consistency
reliability, split-half reliability, test-retest reliability, inter-rater
reliability, structural validity, discriminate validity and criterion validity.
These results provide preliminary evidence that supports the reliability and
validity of the IASToM-aTBI as a ToM assessment tool for adults with TBI.
PMID- 25849663
TI - Increase of microRNA-210, decrease of raptor gene expression and alteration of
mammalian target of rapamycin regulated proteins following mithramycin treatment
of human erythroid cells.
AB - Expression and regulation of microRNAs is an emerging issue in erythroid
differentiation and globin gene expression in hemoglobin disorders. In the first
part of this study microarray analysis was performed both in mithramycin-induced
K562 cells and erythroid precursors from healthy subjects or beta-thalassemia
patients producing low or high levels of fetal hemoglobin. We demonstrated that:
(a) microRNA-210 expression is higher in erythroid precursors from beta
thalassemia patients with high production of fetal hemoglobin; (b) microRNA-210
increases as a consequence of mithramycin treatment of K562 cells and human
erythroid progenitors both from healthy and beta-thalassemia subjects; (c) this
increase is associated with erythroid induction and elevated expression of gamma
globin genes; (d) an anti-microRNA against microRNA-210 interferes with the
mithramycin-induced changes of gene expression. In the second part of the study
we have obtained convergent evidences suggesting raptor mRNA as a putative target
of microRNA-210. Indeed, microRNA-210 binding sites of its 3'-UTR region were
involved in expression and are targets of microRNA-210-mediated modulation in a
luciferase reporter assays. Furthermore, (i) raptor mRNA and protein are down
regulated upon mithramycin-induction both in K562 cells and erythroid progenitors
from healthy and beta-thalassemia subjects. In addition, (ii) administration of
anti-microRNA-210 to K562 cells decreased endogenous microRNA-210 and increased
raptor mRNA and protein expression. Finally, (iii) treatment of K562 cells with
premicroRNA-210 led to a decrease of raptor mRNA and protein. In conclusion,
microRNA-210 and raptor are involved in mithramycin-mediated erythroid
differentiation of K562 cells and participate to the fine-tuning and control of
gamma-globin gene expression in erythroid precursor cells.
PMID- 25849664
TI - Serum metalloproteinase-9 is related to COPD severity and symptoms - cross
sectional data from a population based cohort-study.
AB - BACKGROUND: Chronic obstructive pulmonary disease, COPD, is an increasing cause
of morbidity and mortality worldwide, and an imbalance between proteases and
antiproteases has been implicated to play a role in COPD pathogenesis. Matrix
metalloproteinases (MMP) are important proteases that along with their
inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of
elastin and collagen, of importance for the structural integrity of human
airways. Small observational studies indicate that these biomarkers are involved
in the pathogenesis of COPD. The aim of this study was to investigate serum
levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their
association with disease severity and important clinical symptoms of COPD such as
productive cough. METHODS: Spirometry was performed and peripheral blood samples
were collected in a populations-based cohort (median age 67 years) comprising
subjects with COPD (n = 594) and without COPD (n = 948), in total 1542
individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme
linked immunosorbant assay (ELISA) and related to lung function data and
symptoms. RESULTS: Median serum MMP-9 values were significantly higher in COPD
compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant
differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis,
productive cough and decreasing FEV1% predicted correlated significantly with
increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively),
and FEV1% predicted remained significantly associated to MMP-9 in a multivariate
model adjusting for age, sex, pack years and productive cough (P = 0.033).
CONCLUSION: Productive cough and decreasing FEV1 were each associated with MMP-9
in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also
after adjustment for common confounders in this population-based COPD cohort. The
increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic
activity that is related to disease severity, and further longitudinal studies
are important for the understanding of MMP-9 in relation to the disease process
and the pathogenesis of different COPD phenotypes.
PMID- 25849665
TI - Simultaneous discovery, estimation and prediction analysis of complex traits
using a bayesian mixture model.
AB - Gene discovery, estimation of heritability captured by SNP arrays, inference on
genetic architecture and prediction analyses of complex traits are usually
performed using different statistical models and methods, leading to inefficiency
and loss of power. Here we use a Bayesian mixture model that simultaneously
allows variant discovery, estimation of genetic variance explained by all
variants and prediction of unobserved phenotypes in new samples. We apply the
method to simulated data of quantitative traits and Welcome Trust Case Control
Consortium (WTCCC) data on disease and show that it provides accurate estimates
of SNP-based heritability, produces unbiased estimators of risk in new samples,
and that it can estimate genetic architecture by partitioning variation across
hundreds to thousands of SNPs. We estimated that, depending on the trait, 2,633
to 9,411 SNPs explain all of the SNP-based heritability in the WTCCC diseases.
The majority of those SNPs (>96%) had small effects, confirming a substantial
polygenic component to common diseases. The proportion of the SNP-based variance
explained by large effects (each SNP explaining 1% of the variance) varied
markedly between diseases, ranging from almost zero for bipolar disorder to 72%
for type 1 diabetes. Prediction analyses demonstrate that for diseases with major
loci, such as type 1 diabetes and rheumatoid arthritis, Bayesian methods
outperform profile scoring or mixed model approaches.
PMID- 25849666
TI - Engagement of Fas on Macrophages Modulates Poly I:C induced cytokine production
with specific enhancement of IP-10.
AB - Viral double-stranded RNA (dsRNA) is recognised by pathogen recognition receptors
such as Toll-Like Receptor 3 (TLR3) and retinoic acid inducible gene-I (RIG-I),
and results in cytokine and interferon production. Fas, a well characterised
death receptor, has recently been shown to play a role in the inflammatory
response. In this study we investigated the role of Fas in the anti-viral immune
response. Stimulation of Fas on macrophages did not induce significant cytokine
production. However, activation of Fas modified the response of macrophages to
the viral dsRNA analogue poly I:C. In particular, poly I:C-induced IP-10
production was significantly enhanced. A similar augmentation of IP-10 by Fas was
observed following stimulation with both poly A:U and Sendai virus. Fas
activation suppressed poly I:C-induced phosphorylation of the MAP kinases p38 and
JNK, while overexpression of the Fas adaptor protein, Fas-associated protein with
death domain (FADD), activated AP-1 and inhibited poly I:C-induced IP-10
production. Consistent with an inhibitory role for AP-1 in IP-10 production,
mutation of the AP-1 binding site on the IP-10 promoter resulted in augmented
poly I:C-induced IP-10. These results demonstrate that engagement of the Fas
receptor plays a role in modifying the innate immune response to viral RNA.
PMID- 25849667
TI - Nephrotic syndrome complicated with deep venous thrombosis in the upper
extremities.
AB - Deep venous thrombosis (DVT) in the upper extremities is a rare but important
clinical illness, which leads to severe complications such as pulmonary embolism.
Unlike DVT in the lower extremities, which is mainly induced by a hypercoagulable
state, DVT in the upper extremities is usually caused by mechanical obstruction
or anatomical stenosis in the venous system. We herein report a case in which DVT
developed in the left upper limb during treatment of nephrotic syndrome. This is
the first case report of upper-extremity DVT in association with nephrotic
syndrome in the literature. Our patient was a 56-year-old male with nephrotic
syndrome due to idiopathic membranous nephropathy who was treated with 40 mg/day
of prednisolone. During corticosteroid therapy, he developed a swelling of the
left upper limb. Computed tomography revealed thrombi in the left internal
jugular vein and the left subclavian vein without anatomical abnormalities in his
venous system. Thus, he was diagnosed with DVT of the upper extremities. After
the initiation of warfarin treatment and subsequent regression of nephrotic
syndrome, the swelling disappeared and the thrombi significantly diminished. DVT
should be considered when upper-extremity edema is observed in patients with
nephrotic syndrome.
PMID- 25849668
TI - A Case of IgG2 Heavy Chain Deposition Disease in a Patient with Kappa Positive
Plasma Cell Dyscrasia.
AB - IgG2 heavy chain deposition disease (HCDD) is extremely rare. To date, only 4
cases have been reported in medical literature. To our knowledge, we report the
first case of IgG2 HCDD accompanied by kappa plasma cell dyscrasia.
PMID- 25849669
TI - Minimally Invasive Endourological Techniques may Provide a Novel Method for
Relieving Urinary Obstruction due to Ureterosciatic Herniation.
AB - Ureterosciatic herniation, the protrusion of the hernia sac through the sciatic
foramen, is an extremely rare cause of ureteral obstruction. We describe a case
revealed by severe left back pain in a 72-year-old female. She was referred to
our hospital for urological assessment of left hydronephrosis observed by
ultrasonography. Intravenous ureterography (IVU) showed findings compatible with
a left sciatic ureter, a dilated ureter with a fixed kinking, which is known as
the 'curlicue' sign. We decided to attempt recovery of the herniated ureter using
a retrograde approach. Ureteral stent placement was performed to decompress the
dilated upper urinary tract. The ureterosciatic hernia was relieved with the
passage of a flexible guide wire and a double-pigtail stent. Three months after
ureteral stenting, she refused continuing to have an indwelling stent and the
stent was removed. Thereafter, IVU revealed recurrent ureterosciatic hernia;
however, there was no hydroureter or hydronephrosis. The patient is currently
being under observation for 6 years after stenting and continues to be without
hydronephrosis or symptoms. Placement of an internal stent possibly provides the
rigidity to the ureter, thereby reducing the hernia and urinary obstruction. In
the previous reports, most symptomatic patients have been treated surgically,
with conservative therapy reserved for asymptomatic patients. For the patient who
is elderly or a poor surgical candidate, retrograde stenting may provide safe
reduction and efficacious treatment. This endourological approach provides a
minimally invasive means for the management of urinary obstruction caused by
ureterosciatic herniation.
PMID- 25849670
TI - Posterior reversible encephalopathy syndrome after renal transplant: a simple
solution for a complicated patient.
AB - BACKGROUND: Posterior reversible leukoencephalopathy syndrome (PRES) is
characterized by an acute neurologic dysfunction coupled with characteristic
findings on brain imaging. PRES occurs in the setting of hypertensive
emergencies, eclampsia and as a neurotoxic effect of immunosuppressive agents.
While overwhelmingly reversible without residual deficits when promptly
recognized, vague symptomatology may delay the diagnosis of PRES.
RESULTS/SUMMARY: A 50-year-old man who had undergone a recent kidney transplant
was admitted to our clinic due to multiple episodes of seizure. He had no prior
history of seizures or alcoholism. His transplantation had been without
complication; he was discharged and given prednisone, tacrolimus, mycophenolate,
acyclovir, trimethoprim-sulfamethoxazole, atenolol and enalapril. On the day of
presentation, he experienced a severe headache, blurred vision and tonic-clonic
seizure-like activity. His neurologic examination was limited by sedation,
although no focal deficits were evident. Laboratory studies were unremarkable. A
lumbar puncture revealed normal opening pressure, negative Gram stain, benign CSF
analysis and India ink preparation. An MRI of the brain revealed bilateral
enhancing parietal-occipital lesions, seen prominently on FLAIR sequence.
Tacrolimus and all other medications were continued. The patient remained
afebrile and normotensive and was extubated on the second hospital day. The
patient reported no neurologic symptoms and was discharged on the third hospital
day after a full recovery. CONCLUSIONS: While the outcome of PRES is typically
benign, a delay in diagnosis may lead to permanent neurologic deficits, and
misdiagnosis can be lethal. The cornerstone of treatment is removal of the
offending agent or treatment of the underlying etiology. A clinical picture of
headache, visual abnormalities, altered mentation and seizures is sufficient to
prompt an empiric discontinuation of agents known to cause PRES. Calcineurin
inhibitors such as tacrolimus are known to cause PRES, and in our patient,
discontinuation led to a complete clinical resolution.
PMID- 25849671
TI - A case report on allergic rash caused by icodextrin.
AB - Icodextrin may be used as an alternative to glucose as the osmotic agent in
peritoneal dialysis with ultrafiltration failure. In general, icodextrin is known
to be safe and well tolerated, but it can also cause hypersensitivity reactions
such as skin rashes. Allergic rashes are generally defined as erythematous, itchy
and maculopapular, visible over the trunk and the extremities. When a rash
occurs, it generally develops early in therapy, is self-limited, and resolves
without sequelae after the discontinuation of icodextrin. Although the safety and
efficacy of icodextrin peritoneal dialysis solution is well documented,
clinicians should be aware of the possibility of severe adverse cutaneous
reactions to it. We report the case of a 23-year-old female who developed a skin
rash following the use of icodextrin.
PMID- 25849672
TI - Bucillamine-induced membranous nephropathy with crescent formation in a patient
with rheumatoid arthritis: case report and literature review.
AB - Bucillamine is a disease-modifying antirheumatic drug that is structurally
similar to D-penicillamine. The major renal side effect of bucillamine and D
penicillamine is proteinuria caused by membranous nephropathy (MN). In addition
to MN, combined crescent formation has been occasionally reported in D
penicillamine-induced MN, while crescent formation has been rarely reported in
bucillamine-treated cases. Here, we describe a 76-year-old female who presented
with nephrotic syndrome and rapidly progressive glomerulonephritis. She was
receiving bucillamine as initial treatment for recently diagnosed rheumatoid
arthritis, and renal biopsy showed MN with crescent formation. To the best of our
knowledge, this is the first report of bucillamine-induced MN with crescent
formation in the English literature.
PMID- 25849673
TI - A case of laparoscopic ureteric reimplantation in a solitary urinary system.
AB - Ureteric strictures can be caused by traumatic pelvic surgery, urolithiasis and
instrumentation. There are various treatment options for ureteric stricture,
including laparoscopic ureteric reimplantation. A 56-year-old female with a
history of chronic left pelviureteric junction obstruction presented with
urosepsis secondary to right-sided urolithiasis. The patient had a left
nephrectomy and developed right-sided ureteric stricture following repeated
ureteroscopy to manage her stone disease. The treatment with ureteric stenting
was unsuccessful. Here we present a case on the feasibility of laparoscopic
reimplantation for ureteric stricture in a solitary kidney to preserve renal
function and avoid further ureteroscopy or nephrostomies.
PMID- 25849674
TI - Acute Interstitial Nephritis and Membranous Nephropathy in the Context of IgG4
Related Disease.
AB - We present the case of a patient with IgG4-related disease, which manifested in
an asynchronous manner as vitiligo, cholecystitis, sialadenitis, lymphadenopathy,
facial palsy and kidney dysfunction. The patient underwent a renal biopsy, and a
presumptive diagnosis of lupus nephritis was made due to compatible clinical and
immunological findings. The biopsy revealed IgG4-related kidney disease with
severe interstitial nephritis and membranous nephropathy. Corticosteroids
treatment restored all disease manifestations. We bring this case to the
attention of the nephrologists because of the protean, asynchronous,
multisystemic nature of the disease that necessitates a multidisciplinary
approach, a low threshold for kidney biopsy and a high index of suspicion for
making the correct diagnosis and treatment.
PMID- 25849675
TI - A rare case of low-solute hyponatremia in a nonalcoholic person.
AB - Low-solute hyponatremia is a relatively uncommon entity of euvolemic
hyponatremia. Classic cases were described in alcoholics as beer potomania, which
is characterized by hyponatremia in the setting of low-solute intake due to heavy
beer drinking. We report a case of low-solute hyponatremia in a nonalcoholic
person who was given a solute load, and, subsequently, had excessive diuresis
with the resultant rapid increase in serum sodium concentration.
PMID- 25849676
TI - From cardio pulmonary bypass to ECMO, mechanical assist devices, quality control
and decrease in 30 day mortality in cardiac anaesthesia - are we nearer our goal?
PMID- 25849677
TI - Quality in cardiac anesthesia: is there an alternative to its practice?
PMID- 25849678
TI - Extracorporeal circulation-from cardiopulmonary bypass to extracorporeal membrane
oxygenation and mechanical cardiac assist device therapy: a constant evolution.
PMID- 25849680
TI - 30-day mortality versus 1 year mortality in post cardiac surgery in adults.
PMID- 25849679
TI - 30-day mortality after coronary artery bypass grafting and valve surgery has
greatly improved over the last decade, but the 1-year mortality remains constant.
AB - INTRODUCTION: European system for cardiac operative risk evaluation (EuroSCORE)
is a valuable tool in control of the quality of cardiac surgery. However, the
validity of the risk score for the individual patient may be questioned. The
present study was carried out to investigate whether the continued fall in short
term mortality reflects an actual improvement in late mortality, and
subsequently, to investigate EuroSCORE as predictor of 1-year mortality. METHODS:
A population-based cohort study of 25,602 patients from a 12-year period from
three public university hospitals undergoing coronary artery bypass grafting
(CABG) or valve surgery. Analysis was carried out based on EuroSCORE, age and co
morbidity factors (residual EuroSCORE). RESULTS: During the period the average
age increased from 65.1 +/- 10.0 years to 68.9 +/- 10.7 years (P < 0.001, one-way
ANOVA), and the number of females increased from 26.0% to 28.2% (P = 0.0012, Chi
square test). The total EuroSCORE increased from 4.67 to 5.68 while the residual
EuroSCORE decreased from 2.64 to 1.83. Thirty-day mortality decreased from 4.07%
in 1999-2000 to 2.44% in 2011-2012 (P = 0.0056; Chi-square test), while 1-year
mortality was unchanged (6.50% in 1999-2000 vs. 6.25% in 2011-2012 [P = 0.8086;
Chi-square test]). DISCUSSION: The study demonstrates that both co-morbidity and
age has a great impact on 30-day mortality. However, with time the impact of co
morbidity seems less. Thus, age is more important than co-morbidity in late
mortality. The various developments in short and long-term mortality are not
readily explained. CONCLUSION: Although 30-day mortality of CABG and valve
surgery patients has decreased during the 12-year period, the 1-year mortality
remains the same.
PMID- 25849681
TI - Comparative effects of propofol and nitroglycerine on efficacy of rewarming in
patients undergoing on-pump coronary artery bypass grafting.
AB - OBJECTIVES: To compare the effects of propofol and nitroglycerine (NTG) on the
efficacy of rewarming, extra volume added during cardiopulmonary bypass and
extravascular lung water (EVLW) in patients undergoing on-pump coronary artery
bypass grafting. MATERIALS AND METHODS: A prospective, randomized, blinded trial,
twenty adult patients were randomly assigned to receive either NTG infusion (NTG
group) or propofol infusion (propofol group) during rewarming. RESULTS: After
drop in temperature at the end of surgery and till 24 h were significantly less
in propofol group compare to NTG group (P < 0.025). Extra volume added during
cardiopulmonary bypass and net crystalloid balance till 24 h was less in the
propofol group (P < 0.003). There was no difference in EVLW and postoperative
outcome. CONCLUSIONS: Propofol use during moderate hypothermic cardiopulmonary
bypass is associated with less after drop in temperature and less requirement of
extra fluid during the perioperative period.
PMID- 25849682
TI - Pulmonary hypertension and pregnancy: the experience of a tertiary institution
over 15 years.
AB - BACKGROUND: Pulmonary hypertension (PH) in pregnancy is associated with a high
maternal mortality and morbidity and has been found to be as high as 30-56%. AIM:
To review the management of such patients in a tertiary center over a 15 year
period, as the current literature consists of a few case reports, a few small
case series and 2 meta-analyses. MATERIALS AND METHODS: A review of all patients
admitted to our institution for management of PH in pregnancy between 1994 and
February 2009 was undertaken. Cases were identified from the high-risk pregnancy
database within the department of anesthesia and from the hospital medical
records. Severity of PH, type of PH, NYHA functional status at presentation and
delivery, mode of delivery, peripartum monitoring and APGAR scores were noted.
Patients were reviewed by a multidisciplinary team and management planned
accordingly. RESULTS: 19 eligible patients were identified. Patients who were
significantly sick due to their PH were aggressively managed during pregnancy.
Overall there was an improvement in NYHA functional status at the time of
delivery. Epidural analgesia and anesthesia for labor and operatively delivery
seem to be the ideal choice. CONCLUSION: Multidisciplinary approach is a key to
the successful management of these patients. Secondary PH results in higher
morbidity and mortality, in particular, older the age higher the maternal
morbidity and mortality.
PMID- 25849684
TI - Risk assessment scores in cardiac surgery.
PMID- 25849683
TI - Does Parsonnet scoring model predict mortality following adult cardiac surgery in
India?
AB - AIMS AND OBJECTIVES: To validate the Parsonnet scoring model to predict mortality
following adult cardiac surgery in Indian scenario. MATERIALS AND METHODS: A
total of 889 consecutive patients undergoing adult cardiac surgery between
January 2010 and April 2011 were included in the study. The Parsonnet score was
determined for each patient and its predictive ability for in-hospital mortality
was evaluated. The validation of Parsonnet score was performed for the total data
and separately for the sub-groups coronary artery bypass grafting (CABG), valve
surgery and combined procedures (CABG with valve surgery). The model calibration
was performed using Hosmer-Lemeshow goodness of fit test and receiver operating
characteristics (ROC) analysis for discrimination. Independent predictors of
mortality were assessed from the variables used in the Parsonnet score by
multivariate regression analysis. RESULTS: The overall mortality was 6.3% (56
patients), 7.1% (34 patients) for CABG, 4.3% (16 patients) for valve surgery and
16.2% (6 patients) for combined procedures. The Hosmer-Lemeshow statistic was
<0.05 for the total data and also within the sub-groups suggesting that the
predicted outcome using Parsonnet score did not match the observed outcome. The
area under the ROC curve for the total data was 0.699 (95% confidence interval
0.62-0.77) and when tested separately, it was 0.73 (0.64-0.81) for CABG, 0.79
(0.63-0.92) for valve surgery (good discriminatory ability) and only 0.55 (0.26
0.83) for combined procedures. The independent predictors of mortality determined
for the total data were low ejection fraction (odds ratio [OR] - 1.7),
preoperative intra-aortic balloon pump (OR - 10.7), combined procedures (OR -
5.1), dialysis dependency (OR - 23.4), and re-operation (OR - 9.4). CONCLUSIONS:
The Parsonnet score yielded a good predictive value for valve surgeries, moderate
predictive value for the total data and for CABG and poor predictive value for
combined procedures.
PMID- 25849685
TI - Effect of etomidate and propofol induction on hemodynamic and endocrine response
in patients undergoing coronary artery bypass grafting/mitral valve and aortic
valve replacement surgery on cardiopulmonary bypass.
AB - INTRODUCTION: The concerns for induction of anaesthesia in patients undergoing
cardiac surgery include hemodynamic stability, attenuation of stress response and
maintenance of balance between myocardial oxygen demand and supply. Various
Intravenous anaesthetic agents like Thiopentone, Etomidate, Propofol, Midazolam,
and Ketamine have been used for anesthetizing patients for cardiac surgeries.
However, many authors have expressed concerns regarding induction with
thiopentone, midazolam and ketamine. Hence, Propofol and Etomidate are preferred
for induction in these patients. However, these two drugs have different
characteristics. Etomidate is preferred for patients with poor left ventricular
(LV) function as it provides stable cardiovascular profile. But there are
concerns about reduction in adrenal suppression and serum cortisol levels.
Propofol, on the other hand may cause a reduction in systemic vascular resistance
and subsequent hypotension. Thus, this study was conducted to compare induction
with these two agents in cardiac surgeries. METHODS: Baseline categorical and
continuous variables were compared using Fisher's exact test and student's t test
respectively. Hemodynamic variables were compared using student's t test for
independent samples. The primary outcome (serum cortisol and blood sugar) of the
study was compared using Wilcoxon Rank Sum test. The P value less than 0.05 was
considered significant. RESULTS: Etomidate provides more stable hemodynamic
parameters as compared to Propofol. Propofol causes vasodilation and may result
in drop of systematic BP. Etomidate can therefore be safely used for induction in
patients with good LV function for CABG/MVR/AVR on CPB without serious cortisol
suppression lasting more than twenty-four hours.
PMID- 25849686
TI - Induced apnea enhances image quality and visualization of cardiopulmonary
anatomic during contrastenhanced cardiac computerized tomographic angiography in
children.
AB - OBJECTIVE: The purpose of our study was to determine the effect of induced apnea
on quality of cardiopulmonary structures during computerized tomographic (CT)
angiography images in children with congenital heart diseases. METHODS: Pediatric
patients with congenital heart defects undergoing cardiac CT angiography at our
facility in the past 3 years participated in this study. The earlier patients
underwent cardiac CT angiography without induced apnea and while, later, apnea
was induced in patients, which was followed by electrocardiogram gated cardiac CT
angiography. General anesthesia was induced using sleep dose of intravenous
propofol. After the initial check CT, on request by the radiologist, apnea was
induced by the anesthesiologist by administering 1 mg/kg of intravenous
suxamethonium. Soon after apnea ensued, the contrast was injected, and CT
angiogram carried out. CT images in the "apnea group" were compared with those in
"nonapnea group." After the completion of the procedure, the patients were mask
ventilated with 100% oxygen till the spontaneous ventilation was restored.
RESULTS: We studied 46 patients, of whom 36 with apnea and yet another 10
without. The quality of the image, visualization of structures such as cardiac
wall, outflow tracts, lung field, aortopulmonary shunts, and coronary arteries
were analyzed and subjected to statistical analysis (Mann-Whitney U, Fischer's
exact test and Pearson's Chi-square test). In the induced apnea group, overall
image quality was considered excellent in 89% (n = 33) of the studies, while in
the "no apnea group," only 30% of studies were excellent. Absent or minimal
motion artifacts were seen in a majority of the studies in apnea group (94%). In
the nonapnea group, the respiratory and body motion artifacts were severe in 50%,
moderate in 30%, and minimal in 20%, but they were significantly lesser in the
apnea group. All the studied parameters were statistically significant in the
apnea group in contrast to nonapnea group (P < 0.000). CONCLUSION: The image
quality of cardiac CT angiography greatly improves, and motion artifact
significantly decreases with the use of induced apnea in pediatrics patients
being evaluated for congenital heart disease. This technique poses no additional
morbidity of significance.
PMID- 25849687
TI - Simulation training for extracorporeal membrane oxygenation.
AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a complex treatment.
Despite this, there are a lack of training programs designed to develop relevant
clinical and nonclinical skills required for ECMO specialists. The aim of the
current study was to describe the design, implementation and evaluation of a 1
day simulation course for delivering training in ECMO. METHODS: A 1-day
simulation course was developed with educational and intensive care experts.
First, the delegates received a lecture on the principles of simulation training
and the importance of human factors. This was, followed by a practical
demonstration and discussion of the ECMO circuit, console components, circuit
interactions effects and potential complications. There were then five ECMO
simulation scenarios with debriefing that covered technical and nontechnical
issues. The course culminated in a knowledge-based assessment. Course outcomes
were assessed using purpose-designed questionnaires. RESULTS: We held 3 courses
with a total of 14 delegates (9 intensive care nurses, 3 adult intensive care
consultants and 2 ECMO technicians). Following the course, 8 (57%) gained
familiarity in troubleshooting an ECMO circuit, 6 (43%) increased their
familiarity with the ECMO pump and circuit, 8 (57%) perceived an improvement in
their communication skills and 7 (50%) perceived an improvement in their
leadership skills. At the end of the course, 13 (93%) delegates agreed that they
felt more confident in dealing with ECMO. CONCLUSIONS: Simulation-training
courses may increase knowledge and confidence in dealing with ECMO emergencies.
Further studies are indicated to determine whether simulation training improves
clinical outcomes and translates to reduced complication rates in patients
receiving ECMO.
PMID- 25849688
TI - Transesophageal echocardiography in NeoChord procedure.
AB - BACKGROUND: Transapical off-pump mitral valve intervention with neochord
implantation for degenerative mitral valve disease have been recently introduced
in the surgical practice. The procedure is performed under 2D-3D transesophageal
echocardiography guidance. METHODS: The use of 3D real-time transesophageal
echocardiography provides more accurate information than 2D echocardiography only
in all the steps of the procedure. In particular 3D echocardiography is mandatory
for preoperative assessment of the morphology of the valve, for correct
positioning of the neochord on the diseased segment , for the final tensioning of
the chordae and for the final evaluation of the surgical result. RESULT AND
CONCLUSION: This article is to outline the technical aspects of the
transesophageal echocardiography guidance of the NeoChord procedure showing that
the procedure can be performed only with a close and continuous interaction
between the anesthesiologist and the cardiac surgeon.
PMID- 25849689
TI - Intraoperative transesophageal echocardiographic assessment of left ventricular
Tei index in congenital heart disease.
AB - BACKGROUND: Use of the Tei index has not been described to assess myocardial
function before or after surgery in pediatric patients. This study was designed
to evaluate the left ventricular (LV) function using the Tei index pre- and post
cardiopulmonary bypass in patients with lesion that result in a volume loaded
right ventricle (RV). METHODS: Retrospective data on 55 patients who underwent
repair of a cardiac defect were analyzed. Patients with volume overload RV (n =
15) were compared to patients without volume overload but with other cardiac
defects (n = 40). We reviewed pre- and post-operative LV myocardial performance
index (Tei index). Tei index was obtained from transesophageal Doppler
echocardiogram. RESULTS: Patients with right heart volume overload, the mean
preoperative Tei index was 0.6, with a postoperative mean decrease of 0.207 (P =
0.014). Patients without right heart volume overload, the mean preoperative Tei
was 0.48 with no significant postoperative change (P = 0.82). CONCLUSION: Pre-
and post-operative transesophageal echocardiogram assessment provides an easy and
quick way of evaluating LV function intra-operatively using LV Tei index.
Preoperative LV Tei index was greater in the RV volume overload defects
indicating diminished LV global function. This normalized in the immediate
postoperative period, implying an immediate improvement in LV function. In
patients without right heart volume load, consist of other cardiac defects,
demonstrated no changes in the pre- and post-operative LV Tei. This implies that
LV function was similar after the surgery.
PMID- 25849691
TI - Elevated postoperative serum procalcitonin is not indicative of bacterial
infection in cardiac surgical patients.
AB - BACKGROUND: Identifying infections early, commencing appropriate empiric
antibiotic not only helps gain control early, but also reduces mortality and
morbidity. Conventional cultures take about 5 days to identify infections. To
identify the infections early biomarker like serum procalcitonin (SPC). AIMS: We
studied the correlation of an elevated level of SPC and positive culture in
elective adult patients undergoing cardiac surgery. METHODS: This prospective
study was conducted from January to December 2013. SPC was checked in patients
showing evidence of sepsis. Simultaneously, relevant culture was also undertaken.
Correlation, specificity, and sensitivity of elevated SPC were checked. RESULTS:
A total of 819 adult patients were included in the study. 43 of them had signs of
infection and SPC levels were checked. Based on the level of SPC criteria, 10
patients were diagnosed as "nil", out of them, 4 had culture-positive infections,
17 were suggested to have "mild infection," 3 out those had culture positivity.
None among the eleven patients suggested to have "moderate infection," had a
positive culture, and one among the five suggested to have a severe infection had
a positive culture. The sensitivity was 50% and the specificity 17%. The positive
predictive value was 12% and the negative predictive value 60%. CONCLUSIONS: We
failed to elicit positive correlation between elevated SPC levels and
postoperative infection in cardio surgical patients.
PMID- 25849692
TI - Video commentary on "ECMO for heart failure and post heart transplant".
PMID- 25849690
TI - Ketamine in adult cardiac surgery and the cardiac surgery Intensive Care Unit: an
evidence-based clinical review.
AB - Ketamine is a unique anesthetic drug that provides analgesia, hypnosis, and
amnesia with minimal respiratory and cardiovascular depression. Because of its
sympathomimetic properties it would seem to be an excellent choice for patients
with depressed ventricular function in cardiac surgery. However, its use has not
gained widespread acceptance in adult cardiac surgery patients, perhaps due to
its perceived negative psychotropic effects. Despite this limitation, it is
receiving renewed interest in the United States as a sedative and analgesic drug
for critically ill-patients. In this manuscript, the authors provide an evidence
based clinical review of ketamine use in cardiac surgery patients for intensive
care physicians, cardio-thoracic anesthesiologists, and cardio-thoracic surgeons.
All MEDLINE indexed clinical trials performed during the last 20 years in adult
cardiac surgery patients were included in the review.
PMID- 25849693
TI - Video commentary on "imaging the coronary sinus".
PMID- 25849694
TI - Single lumen tube as endobronchial stent to manage left bronchial compression
post total anomalous pulmonary venous connection repair.
PMID- 25849695
TI - Is it really ruptured sinus of valsalva? The crucial role of comprehensive
transesophageal echocardiography in clinical decision-making.
PMID- 25849696
TI - Rational interpretation of transesophageal echocardiography hemodynamics in the
Intensive Care Unit, post aortic valve replacement.
PMID- 25849698
TI - A novel technique of anesthesia induction in supine position with impaled knife
in the back.
AB - Current technique of airway management for impaled knife in the back includes
putting the patient in lateral position and intubation. We present here a novel
technique of anesthesia induction (intubation and central line insertion) in a
patient with impaled knife in the back which is simple and easily reproducible.
This technique can be used for single lung ventilation using double lumen tube or
bronchial blocker also if desired.
PMID- 25849697
TI - Echocardiographic detection of intimo-intimal intussusception in a patient with
acute Stanford type A aortic dissection.
AB - Intimo-intimal intussusception is a very rare and unusual complication of type A
dissections, typically noted on TEE exam. It has been reported in a few cases in
the cardiothoracic surgical and radiology literature, and even more rarely in the
cardiac anesthesia/TEE literature. This uncommon variation occurs in severe,
acute, type A dissections when the ascending aortic intima circumferentially
strips and detaches from the media and forms a tube-like structure which may
either prolapse antegrade into the ascending aortic lumen or retrograde into the
left ventricular (LV) outflow tract and LV cavity. Antegrade intussusceptions may
be severe enough to partially or completely occlude the ostia of the innominate,
left common carotid, and left subclavian arteries producing acute neurologic
symptoms. Retrograde intussusceptions may severely impair LV filling in diastole,
can worsen aortic insufficiency, mitral regurgitation, as well as produce
occlusion of the coronary ostia and acute coronary ischemia. Here, we describe
the incidental finding of a retrograde intussusception that was not visualized on
computed tomography scan but by intraoperative TEE examination, in a patient with
a severe, extensive type A dissection.
PMID- 25849699
TI - Role of perioperative transesophageal echocardiography in the management of
adolescent truncus arteriosus: rare case report.
AB - Truncus arteriosus (TA) is a rare congenital heart disease defined as a single
arterial vessel arising from the heart that gives origin to the systemic,
pulmonary and coronary circulations. The truncal valve in majority of the cases
is tricuspid though quadricuspid and bicuspid valves have been reported. Patients
with TA typically have a large nonrestrictive sub truncal ventricular septal
defect. Survival of these infants beyond 1-year is uncommon. Here, we report a
unique case of 12-year-old female patient with persistent TA who underwent
surgical repair by using transesophageal echocardiography as a monitoring device
during the perioperative management.
PMID- 25849700
TI - Feasibility and safety of on table extubation after corrective surgical repair of
tetralogy of Fallot in a developing country: a case series.
AB - Fast-track extubation is an established safe practice in pediatric congenital
heart disease (CHD) surgical patients. On table extubation (OTE) in acyanotic CHD
surgical patients is well established with validated safety profile. This
practice is not yet reported in tetralogy of Fallot (TOF) cardiac surgical repair
patients in developing countries. Evidence suggests that TOF total correction
patients should be extubated early, as positive pressure ventilation has a
negative impact on right ventricular function and the overall increase in post
TOF repair complications such as low cardiac output state and arrhythmias. The
objective of the case series was to determine the safety and feasibility of OTE
in elective TOF total correction cardiac surgical patients with an integrated
team approach. To the best of our knowledge, this is the first reported case
series. A total of 8 elective male and female TOF patients were included.
Standard anesthetic, surgical and perfusion techniques were used in these
procedures. All patients were extubated in the operating room safely without any
complications with the exception of one patient who continued to bleed for 3 h of
postextubation at 2-3 ml/kg/h which was managed with transfusion of fresh frozen
plasma at 15 mL/kg, packed red blood cells 10 mL/kg and bolus of transamine at 20
mg/kg. Apart from better surgical and bypass techniques, the most important
factor leading to successful OTE was an excellent analgesia. On the basis of the
case series, it is suggested to extubate selected TOF cardiac surgery repair
patients on table safely with integrated multidisciplinary approach.
PMID- 25849701
TI - Perioperative intra-aortic balloon counterpulsation in a patient with myocardium
at risk undergoing urgent noncardiac surgery.
AB - We are presenting the case of a 76-year-old female scheduled for major abdominal
surgery. Her past medical history was remarkable for a three-vessel coronary
artery disease, with a severely impaired left ventricular function. She had
already undergone complex coronary artery bypass surgery. Currently, she
presented with the rare constellation of a hemodynamic relevant and
interventionally intractable stenosis of the left subclavian artery proximal to a
crucial coronary bypass from left internal mammary artery to the left anterior
descending. To protect this patient from perioperative myocardial infarction, an
intra-aortic balloon pump was successfully used.
PMID- 25849702
TI - Transcatheter, valve-in-valve transapical aortic and mitral valve implantation,
in a high risk patient with aortic and mitral prosthetic valve stenoses.
AB - Transcatheter valve implantation continues to grow worldwide and has been used
principally for the nonsurgical management of native aortic valvular disease-as a
potentially less invasive method of valve replacement in high-risk and inoperable
patients with severe aortic valve stenosis. Given the burden of valvular heart
disease in the general population and the increasing numbers of patients who have
had previous valve operations, we are now seeing a growing number of high-risk
patients presenting with prosthetic valve stenosis, who are not potential
surgical candidates. For this high-risk subset transcatheter valve delivery may
be the only option. Here, we present an inoperable patient with severe,
prosthetic valve aortic and mitral stenosis who was successfully treated with a
trans catheter based approach, with a valve-in-valve implantation procedure of
both aortic and mitral valves.
PMID- 25849703
TI - Laparoscopic colectomy in an adult with single ventricle physiology: anesthetic
implications and management.
AB - Increasing numbers of adult patients with complex congenital heart conditions are
presenting for noncardiac surgery later in life. These disorders can present
challenges for surgical and anesthesia providers. Specifically, single ventricle
lesions offer anatomic and physiologic concerns during the perioperative period.
Single ventricle physiology represents a delicate balance between systemic and
pulmonary blood flow. Any alterations in blood flow through these systems can
produce undesirable hemodynamic changes, especially during the perioperative
period. We present a case of an adult patient with a single left ventricle who
presented for laparoscopic total colectomy due to inflammatory bowel disease. His
abnormal anatomy coupled with the hemodynamic disruptions caused by laparoscopy
presented significant anesthetic challenges. We highlight the anesthetic concerns
of single ventricle physiology, specifically pertaining to laparoscopic surgery.
We provide recommendations for safely managing these patients perioperatively.
With detailed preoperative evaluation and close hemodynamic monitoring during the
perioperative period, these patients can experience successful surgical and
anesthetic outcomes.
PMID- 25849704
TI - Anticoagulation dilemma in a high-risk patient with On-X valves.
AB - Thromboembolism continues to be a major concern in patients with mechanical heart
valves, especially in those with unsatisfactory anticoagulation levels. The new
On-X valve (On-X Life Technologies, Austin, TX, USA) has been reported as having
unique structural characteristics that offer lower thrombogenicity to the valve.
We report a case where the patient received no or minimal systemic
anticoagulation after placement of On-X mitral and aortic valves due to
development of severe mucosal arterio-venous malformations yet did not show any
evidence of thromboembolism. This case report reinforces the findings of recent
studies that lower anticoagulation levels may be acceptable in patients with On-X
valves and suggests this valve may be particularly useful in those in whom
therapeutic levels of anticoagulation cannot be achieved due to increased risk of
bleeding.
PMID- 25849705
TI - Combined etiology of anaphylactic cardiogenic shock: amiodarone, epinephrine,
cardioverter defibrillator, left ventricular assist devices and the Kounis
syndrome.
AB - Anaphylactic shock is a life-threatening condition which needs detailed and
mediculous clinical assessment and thoughtful treatment. Several causes can join
forces in order to degranulate mast cells. Amiodarone which is an iodine
containing highly lipophilic benzofuran can induce allergic reactions and
anaphylactic shock in sensitized patients. Epinephrine is a life saving drug, but
in sulfite allergic patients it should be given with caution due its
metabisulfite preservative. Metals covering cardiac defibrillators and pacemakers
can act as antigens attached to serum proteins and induce allergic reactions. In
anaphylactic shock, myocardial involvement due to vasospasm-induced coronary
blood flow reduction manifesting as Kounis syndrome should be always considered.
Clinically, combined treatment targeting the primary cause of anaphylaxis
together with protection of cardiac tissue seems to be of paramount importance.
PMID- 25849706
TI - Cardiac myxoma: a shadow cast elsewhere.
PMID- 25849707
TI - Intravenous regional anesthesia as an anesthetic technique for a patient with
ventricular bigeminy.
PMID- 25849708
TI - Right main bronchus bulge after capnothorax for thoracoscopic esophagectomy: an
interesting finding on fiber-optic bronchoscopy through a double lumen tube!
PMID- 25849709
TI - Malposition of a nasogastric tube.
PMID- 25849710
TI - Flambeau in the left atrium.
PMID- 25849711
TI - Entrapped left atrial pressure monitoring catheter in a prosthetic mitral valve.
PMID- 25849712
TI - Calcium-catalyzed asymmetric synthesis of 3-tetrasubstituted oxindoles: efficient
construction of adjacent quaternary and tertiary chiral centers.
AB - Chiral Ca-catalyzed asymmetric addition reactions of 3-substituted oxindoles with
N-Boc-imines afford 3-tetrasubstituted oxindole derivatives bearing adjacent
quaternary and tertiary chiral centers, which are key structures for biological
activities. Ubiquitous and nontoxic Ca catalysts (1-10 mol %) work well in this
reaction, and high yields (up to 99%) and selectivities (up to >99% ee) of the
products with wide substrate scope have been attained. The structures of the
chiral Ca catalysts and intermediary Ca enolates are also discussed.
PMID- 25849714
TI - Extraction of crude polysaccharides from Duchesnea indica (Andrews) Focke:
optimization by response surface methodology.
AB - A full set of optimization procedure was applied to the extraction of anti-viral
polysaccharides from Duchesnea indica (Andrews) Focke. By Plackett-Burman
factorial design, three parameters (extraction time, extraction temperature, and
ratio of water to raw material) were identified as significant to the extraction
yield. However, no significant parameters had been identified for antiviral
activity. A three-level-three-factor Box-Behnken factorial design was then
employed to further optimize the extraction condition. The experimental data were
fitted to a second-order polynomial equation using multiple regression analysis
and also examined using appropriate statistical methods. This led to the
construction of a response surface indicating the optimal values for each
parameter and response studied. Concerning the extraction yield, an extraction at
98.51 oC for 6.16 h with a ratio of water to raw material of 30.94 mL/g was found
to be optimal. Under the optimized conditions, the experimental yield was 6.430
+/- 0.078%, which was well matched with the predicted yield of 6.509%.
PMID- 25849715
TI - Causal effects of time-dependent treatments in older patients with non-small cell
lung cancer.
AB - BACKGROUND: Treatment selection for elderly patients with lung cancer must
balance the benefits of curative/life-prolonging therapy and the risks of
increased mortality due to comorbidities. Lung cancer trials generally exclude
patients with comorbidities and current treatment guidelines do not specifically
consider comorbidities, so treatment decisions are usually made on subjective
individual-case basis. METHODS: Impacts of surgery, radiation, and chemotherapy
mono-treatment as well as combined chemo/radiation on one-year overall survival
(compared to no-treatment) are studied for stage-specific lung cancer in 65+ y.o.
patients. Methods of causal inference such as propensity score with inverse
probability weighting (IPW) for time-independent and marginal structural model
(MSM) for time-dependent treatments are applied to SEER-Medicare data considering
the presence of comorbid diseases. RESULTS: 122,822 patients with stage I
(26.8%), II (4.5%), IIIa (11.5%), IIIb (19.9%), and IV (37.4%) lung cancer were
selected. Younger age, smaller tumor size, and fewer baseline comorbidities
predict better survival. Impacts of radio- and chemotherapy increased and impact
of surgery decreased with more advanced cancer stages. The effects of all
therapies became weaker after adjustment for selection bias, however, the changes
in the effects were minor likely due to the weak selection bias or incompleteness
of the list of predictors that impacted treatment choice. MSM provides more
realistic estimates of treatment effects than the IPW approach for time
independent treatment. CONCLUSIONS: Causal inference methods provide substantive
results on treatment choice and survival of older lung cancer patients with
realistic expectations of potential benefits of specific treatments. Applications
of these models to specific subsets of patients can aid in the development of
practical guidelines that help optimize lung cancer treatment based on individual
patient characteristics.
PMID- 25849716
TI - Inherent transcriptional signatures of NK cells are associated with response to
IFNalpha + rivabirin therapy in patients with Hepatitis C Virus.
AB - BACKGROUND: Differences in the expression of Natural Killer cell receptors have
been reported to reflect divergent clinical courses in patients with chronic
infections or tumors. However, extensive molecular characterization at the
transcriptional level to support this view is lacking. The aim of this work was
to characterize baseline differences in purified NK cell transcriptional activity
stratified by response to treatment with PEG-IFNalpha/RBV in patients chronically
infected with HCV. METHODS: To this end we here studied by flow cytometer and
gene expression profile, phenotypic and transcriptional characteristics of
purified NK cells in patients chronically infected with HCV genotype-1 virus who
were subsequently treated with PEG-IFNalpha/RBV. Results were further correlated
with divergent clinical response obtained after treatment. RESULTS: The pre
treatment transcriptional patterns of purified NK cells from patients
subsequently undergoing a sustained virologic response (SVR) clearly segregated
from those of non-responder (NR) patients. A set of 476 transcripts, including
molecules involved in RNA processing, ubiquitination pathways as well as HLA
class II signalling were differently expressed among divergent patients. In
addition, treatment outcome was associated with differences in surface expression
of NKp30 and NKG2D. A complex relationship was observed that suggested for
extensive post-transcriptional editing. Only a small number of the NK cell
transcripts identified were correlated with chronic HCV infection/replication
indicating that inherent transcriptional activity prevails over environment
effects such as viral infection. CONCLUSIONS: Collectively, inherent/genetic
modulation of NK cell transcription is involved in setting the path to divergent
treatment outcomes and could become useful to therapeutic advantage.
PMID- 25849717
TI - Endoplasmic reticulum stress is increased in adipose tissue of women with
gestational diabetes.
AB - Maternal obesity and gestational diabetes mellitus (GDM) are two increasingly
common and important obstetric complications that are associated with severe long
term health risks to mothers and babies. IL-1beta, which is increased in obese
and GDM pregnancies, plays an important role in the pathophysiology of these two
pregnancy complications. In non-pregnant tissues, endoplasmic (ER) stress is
increased in diabetes and can induce IL-1beta via inflammasome activation. The
aim of this study was to determine whether ER stress is increased in omental
adipose tissue of women with GDM, and if ER stress can also upregulate
inflammasome-dependent secretion of IL-1beta. ER stress markers IRE1alpha, GRP78
and XBP-1s were significantly increased in adipose tissue of obese compared to
lean pregnant women. ER stress was also increased in adipose tissue of women with
GDM compared to BMI-matched normal glucose tolerant (NGT) women. Thapsigargin, an
ER stress activator, induced upregulated secretion of mature IL-1alpha and IL
1beta in human omental adipose tissue explants primed with bacterial endotoxin
LPS, the viral dsRNA analogue poly(I:C) or the pro-inflammatory cytokine TNF
alpha. Inhibition of capase-1 with Ac-YVAD-CHO resulted in decreased IL-1alpha
and IL-1beta secretion, whereas inhibition of pannexin-1 with carbenoxolone
suppressed IL-1beta secretion only. Treatment with anti-diabetic drugs metformin
and glibenclamide also reduced IL-1alpha and IL-1beta secretion in infection and
cytokine-primed adipose tissue. In conclusion, this study has demonstrated ER
stress to activate the inflammasome in pregnant adipose tissue. Therefore,
increased ER stress may contribute towards the pathophysiology of obesity in
pregnancy and GDM.
PMID- 25849719
TI - Diagnostics are the vanguard of medicine.
PMID- 25849718
TI - High seroprevalence for spotted fever group rickettsiae, is associated with
higher temperatures and rural environment in Mbeya region, Southwestern Tanzania.
AB - BACKGROUND: Rickettsioses are endemic in sub-Sahara Africa. Burden of disease,
risk factors and transmission are hitherto sparsely described. METHODS: From the
EMINI (Evaluating and Monitoring the Impact of New Interventions) population
cohort, we randomly selected 1,228 persons above the age of 5 years from the nine
participating communities in Mbeya region, Southwestern Tanzania, stratified by
age, altitude of residence and ownership of domestic mammals, to conduct a cross
sectional seroprevalence study in. The aim was to estimate the seroprevalence of
IgG antibodies against Spotted Fever Group (SFG) rickettsiae and to assess
socioeconomic and environmental risk factors. Serology (indirect
immunofluorescence) was performed at a dilution of 1:64. RESULTS: SFG
seropositivity in the cohort was found to be 67.9% (range among nine sites: 42.8
91.4%). Multivariable analysis revealed an association with age (prevalence
ratio, PR per 10 years: 1.08; 95% CI 1.06-1.10), warmer temperatures (PR per
degrees C: 1.38; 1.11-1.71), male gender (PR 1.08; 1.00-1.16), and low population
density (PR per 1.000 persons/km2increase 0.96; 0.94-0.99). At higher elevations,
higher cattle density was associated with higher seroprevalence. CONCLUSION: SFG
rickettsial infection seems to be common in the more rural population of Mbeya
Region. Spread seems to be further limited by temperature and higher elevation.
Examination of the contribution of SFG to febrile illnesses seems warranted in a
prospective study to estimate the disease burden in the population. This will
also allow determination of the causative pathogens.
PMID- 25849720
TI - Participating in next generation sequencing.
PMID- 25849722
TI - Robust molecular bowl-based metal-organic frameworks with open metal sites: size
modulation to increase the catalytic activity.
AB - Herein, two stable lead(II) molecular-bowl-based metal-organic frameworks and
their micro- and nanosized forms with open metal sites were presented. These
materials could act as Lewis acid catalysts to cyanosilylation reaction.
Moreover, the catalytic performances are size-dependent, with the catalyst with
nanosized form being 1 order of magnitude more efficient than those with micro-
and millisized forms.
PMID- 25849721
TI - Changes in insulin receptor signaling underlie neoadjuvant metformin
administration in breast cancer: a prospective window of opportunity neoadjuvant
study.
AB - INTRODUCTION: The antidiabetic drug metformin exhibits potential anticancer
properties that are believed to involve both direct (insulin-independent) and
indirect (insulin-dependent) actions. Direct effects are linked to activation of
AMP-activated protein kinase (AMPK) and an inhibition of mammalian target of
rapamycin mTOR signaling, and indirect effects are mediated by reductions in
circulating insulin, leading to reduced insulin receptor (IR)-mediated signaling.
However, the in vivo impact of metformin on cancer cell signaling and the factors
governing sensitivity in patients remain unknown. METHODS: We conducted a
neoadjuvant, single-arm, "window of opportunity" trial to examine the clinical
and biological effects of metformin on patients with breast cancer. Women with
untreated breast cancer who did not have diabetes were given 500 mg of metformin
three times daily for >=2 weeks after diagnostic biopsy until surgery. Fasting
blood and tumor samples were collected at diagnosis and surgery. Blood glucose
and insulin were assayed to assess the physiologic effects of metformin, and
immunohistochemical analysis of tumors was used to characterize cellular markers
before and after treatment. RESULTS: Levels of IR expression decreased
significantly in tumors (P = 0.04), as did the phosphorylation status of protein
kinase B (PKB)/Akt (S473), extracellular signal-regulated kinase 1/2 (ERK1/2,
T202/Y204), AMPK (T172) and acetyl coenzyme A carboxylase (S79) (P = 0.0001, P <
0.0001, P < 0.005 and P = 0.02, respectively). All tumors expressed organic
cation transporter 1, with 90% (35 of 39) exhibiting an Allred score of 5 or
higher. CONCLUSIONS: Reduced PKB/Akt and ERK1/2 phosphorylation, coupled with
decreased insulin and IR levels, suggest insulin-dependent effects are important
in the clinical setting. These results are consistent with beneficial anticancer
effects of metformin and highlight key factors involved in sensitivity, which
could be used to identify patients with breast cancer who may be responsive to
metformin-based therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
NCT00897884. Registered 8 May 2009.
PMID- 25849723
TI - Matrix metalloproteinase-9 expression is enhanced in renal parietal epithelial
cells of zucker diabetic Fatty rats and is induced by albumin in in vitro primary
parietal cell culture.
AB - As a subfamily of matrix metalloproteinases (MMPs), gelatinases including MMP-2
and MMP-9 play an important role in remodeling and homeostasis of the
extracellular matrix. However, conflicting results have been reported regarding
their expression level and activity in the diabetic kidney. This study
investigated whether and how MMP-9 expression and activity were changed in
glomerular epithelial cells upon albumin overload. In situ zymography,
immunostaining and Western blot for renal MMP gelatinolytic activity and MMP-9
protein expression were performed in Zucker lean and Zucker diabetic rats.
Confocal microscopy revealed a focal increase in gelatinase activity and MMP-9
protein in the glomeruli of diabetic rats. Increased glomerular MMP-9 staining
was mainly observed in hyperplastic parietal epithelial cells (PECs) expressing
claudin-1 in the diabetic kidneys. Interestingly, increased parietal MMP-9 was
often accompanied by decreased staining for podocyte markers (nephrin and
podocalyxin) in the sclerotic area of affected glomeruli in diabetic rats.
Additionally, urinary excretion of podocyte marker proteins was significantly
increased in association with the levels of MMP-9 and albumin in the urine of
diabetic animals. To evaluate the direct effect of albumin on expression and
activity of MMP-9, primary cultured rat glomerular PECs were incubated with rat
serum albumin (0.25 - 1 mg/ml) for 24 - 48 hrs. MMP-9 mRNA levels were
significantly increased following albumin treatment. Meanwhile, albumin
administration resulted in a dose-dependent increase in MMP-9 protein and
activity in culture supernatants of PECs. Moreover, albumin activated p44/42
mitogen-activated protein kinase (MAPK) in PECs. Inhibition of p44/42 MAPK
suppressed albumin-induced MMP-9 secretion from glomerular PECs. Taken together,
we have demonstrated that an up-regulation of MMP-9 in activated parietal
epithelium is associated with a loss of adjacent podocytes in progressive
diabetic nephropathy. Albumin overload may induce MMP-9 expression and secretion
by PECs via the activation of p44/42 MAPK pathway.
PMID- 25849725
TI - High-throughput, quantitative enzyme kinetic analysis in microdroplets using
stroboscopic epifluorescence imaging.
AB - Droplet-based microfluidic systems offer a range of advantageous features for the
investigation of enzyme kinetics, including high time resolution and the ability
to probe extremely large numbers of discrete reactions while consuming low sample
volumes. Kinetic measurements within droplet-based microfluidic systems are
conventionally performed using single point detection schemes. Unfortunately,
such an approach prohibits the measurement of an individual droplet over an
extended period of time. Accordingly, we present a novel approach for the
extensive characterization of enzyme-inhibitor reaction kinetics within a single
experiment by tracking individual and rapidly moving droplets as they pass
through an extended microfluidic channel. A series of heterogeneous and pL-volume
droplets, containing varying concentrations of the fluorogenic substrate
resorufin beta-d-galactopyranoside and a constant amount of the enzyme beta
galactosidase, is produced at frequencies in excess of 150 Hz. By stroboscopic
manipulation of the excitation laser light and adoption of a dual view detection
system, "blur-free" images containing up to 150 clearly distinguishable droplets
per frame are extracted, which allow extraction of kinetic data from all formed
droplets. The efficiency of this approach is demonstrated via a Michaelis-Menten
analysis which yields a Michaelis constant, Km, of 353 MUM. Additionally, the
dissociation constant for the competitive inhibitor isopropyl beta-d-1
thiogalactopyranoside is extracted using the same method.
PMID- 25849724
TI - TASK-1 Potassium Channels Limit Pancreatic alpha-Cell Calcium Influx and Glucagon
Secretion.
AB - Glucose regulation of pancreatic alpha-cell Ca(2+) entry through voltage
dependent Ca(2+) channels is essential for normal glucagon secretion and becomes
defective during the pathogenesis of diabetes mellitus. The 2-pore domain K(+)
channel, TWIK-related acid-sensitive K(+) channel 1 (TASK-1), is an important
modulator of membrane voltage and Ca(2+) entry. However, its role in alpha-cells
has not been determined. Therefore, we addressed how TASK-1 channels regulate
alpha-cell electrical activity, Ca(2+) entry, and glucagon secretion. We find
that TASK-1 channels expressed in human and rodent alpha-cells are blocked by the
TASK-1 channel inhibitor A1899. Alpha-cell 2-pore domain K(+) currents were also
significantly reduced after ablation of mouse alpha-cell TASK-1 channels.
Inhibition of TASK-1 channels with A1899 caused plasma membrane potential
depolarization in both human and mouse alpha-cells, which resulted in increased
electrical excitability. Moreover, ablation of alpha-cell TASK-1 channels
increased alpha-cell electrical excitability under elevated glucose (11 mM)
conditions compared with control alpha-cells. This resulted in significantly
elevated alpha-cell Ca(2+) influx when TASK-1 channels were inhibited in the
presence of high glucose (14 mM). However, there was an insignificant change in
alpha-cell Ca(2+) influx after TASK-1 inhibition in low glucose (1 mM). Glucagon
secretion from mouse and human islets was also elevated specifically in high (11
mM) glucose after acute TASK-1 inhibition. Interestingly, mice deficient for
alpha-cell TASK-1 showed improvements in both glucose inhibition of glucagon
secretion and glucose tolerance, which resulted from the chronic loss of alpha
cell TASK-1 currents. Therefore, these data suggest an important role for TASK-1
channels in limiting alpha-cell excitability and glucagon secretion during
glucose stimulation.
PMID- 25849726
TI - Lung inflammatory pattern and antibiotic treatment in pneumonia.
AB - BACKGROUND: In community-acquired pneumonia host inflammatory response against
the causative microorganism is necessary for infection resolution. However an
excessive response can have deleterious effects. In addition to antimicrobial
effects, macrolide antibiotics are known to possess immunomodulatory properties.
METHODS: A prospective study was performed on 52 admitted patients who developed
an inadequate response after 72 hours of antibiotic treatment - non-responders
community-acquired pneumonia - (blood and bronchoalveolar lavage), and two
control groups: 1) community-acquired pneumonia control (blood) and 2) non
infection control (blood and bronchoalveolar lavage). Cytokine profiles
(interleukin (IL)-6, IL-8, IL-10), tumour necrosis factor alpha and clinical
outcomes were assessed. RESULTS: Non-responders patients treated with macrolide
containing regimens showed significantly lower levels of IL-6 and TNF-alpha in
bronchoalveolar lavage fluid and lower IL-8 and IL-10 in blood than those
patients treated with non-macrolide regimens. Clinical outcomes showed that
patients treated with macrolide regimens required fewer days to reach clinical
stability (p < 0.01) and shorter hospitalization periods (p < 0.01). CONCLUSIONS:
After 72 hours of antibiotic effect, patients who received macrolide containing
regimens exhibited lower inflammatory cytokine levels in pulmonary and systemic
compartments along with faster stabilization of infectious parameters.
PMID- 25849727
TI - GnRH Regulates Gonadotropin Gene Expression Through NADPH/Dual Oxidase-Derived
Reactive Oxygen Species.
AB - The appropriate control of synthesis and secretion of the gonadotropin hormones
LH and FSH by pituitary gonadotropes is essential for the regulation of
reproduction. The hypothalamic neuropeptide GnRH is the central regulator of both
processes, coordinating secretion with transcription and translation of the
gonadotropin hormone subunit genes. The MAPK family of second messengers is
strongly induced in gonadotropes upon GnRH stimulation, and multiple pathways
activate these kinases. Intracellular reactive oxygen species participate in
signaling cascades that target MAPKs, but also participate in signaling events
indicative of cell stress. The NADPH oxidase (NOX)/dual oxidase (DUOX) family is
a major enzymatic source of intracellular reactive oxygen, and we show that GnRH
stimulation of mouse primary pituitary cells and the LbetaT2 gonadotrope cell
line elevates intracellular reactive oxygen via NOX/DUOX activity. Mouse
pituitary and LbetaT2 cells abundantly express NOX/DUOX and cofactor mRNAs.
Pharmacological inhibition of NOX/DUOX activity diminishes GnRH-stimulated
activation of MAPKs, immediate-early gene expression, and gonadotropin subunit
gene expression. Inhibitor studies implicate the calcium-activated DUOX family as
a major, but not exclusive, participant in GnRH signaling. Knockdown of DUOX2 in
LbetaT2 cells reduces GnRH-induced Fshb, but not Lhb mRNA levels, suggesting
differential sensitivity to DUOX activity. Finally, GnRH pulse-stimulated FSH and
LH secretion are suppressed by inhibition of NOX/DUOX activity. These results
indicate that reactive oxygen is a potent signaling intermediate produced in
response to GnRH stimulation and further suggest that reactive oxygen derived
from other sources may influence the gonadotrope response to GnRH stimulation.
PMID- 25849729
TI - Oocyte induction of EGF responsiveness in somatic cells is associated with the
acquisition of porcine oocyte developmental competence.
AB - Oocytes progressively acquire the competence to support embryo development as
oogenesis proceeds with ovarian folliculogenesis. The objectives of this study
were to investigate oocyte-secreted factor (OSF) participation in the development
of somatic cell epidermal growth factor (EGF) responsiveness associated with
oocyte developmental competence. A well-established porcine model was employed
using oocytes from small (<4 mm) vs medium sized (>4 mm) antral follicles,
representing low vs moderate developmental competence, respectively. Cumulus
oocyte complexes (COCs) were treated in vitro with inducers of oocyte maturation,
and cumulus cell functions and oocyte developmental competence were assessed.
COCs from small follicles responded to FSH but, unlike COCs from larger
follicles, were incapable of responding to EGF family growth factors known to
mediate oocyte maturation in vivo, exhibiting perturbed cumulus expansion and
expression of associated transcripts (HAS2 and TNFAIP6). Low and moderate
competence COCs expressed equivalent levels of EGF receptor (EGFR) mRNA; however,
the former had less total EGFR protein leading to failed activation of phospho
EGFR and phospho-ERK1/2, despite equivalent total ERK1/2 protein levels. Native
OSFs from moderate, but not from low, competence oocytes established EGF
responsiveness in low competence COCs. Four candidate recombinant OSFs failed to
mimic the actions of native OSFs in regulating cumulus expansion. Treatment with
OSFs and EGF enhanced oocyte competence but only of the low competence COCs.
These data suggest that developmental acquisition by the oocyte of capacity to
regulate EGF responsiveness in the oocyte's somatic cells is a major milestone in
the oocyte's developmental program and contributes to coordinated oocyte and
somatic cell development.
PMID- 25849728
TI - CYP7B1 Enzyme Deletion Impairs Reproductive Behaviors in Male Mice.
AB - In addition to androgenic properties mediated via androgen receptors,
dihydrotestosterone (DHT) also regulates estrogenic functions via an alternate
pathway. These estrogenic functions of DHT are mediated by its metabolite 5alpha
androstane-3beta, 17beta-diol (3beta-diol) binding to estrogen receptor beta
(ERbeta). CYP7B1 enzyme converts 3beta-diol to inactive 6alpha- or 7alpha-triols
and plays an important role as a regulator of estrogenic functions mediated by
3beta-diol. Using a mutant mouse carrying a null mutation for the CYP7B1 gene
(CYP7B1KO), we examined the contribution of CYP7B1 on physiology and behavior.
Male, gonadectomized (GDX) CYP7B1KO and their wild type (WT) littermates were
assessed for their behavioral phenotype, anxiety-related behavioral measures, and
hypothalamic pituitary adrenal axis reactivity. No significant effects of
genotype were evident in anxiety-like behaviors in open field (OFA), light-dark
(L/D) exploration, and elevated plus maze (EPM). T significantly reduced open arm
time on the EPM while not affecting L/D exploratory and OFA behaviors in CYP7B1KO
and WT littermates. T also attenuated the corticosterone response to EPM in both
genotypes. In GDX animals, T was able to reinstate male-specific reproductive
behaviors (latencies and number of mounts, intromission, and ejaculations) in the
WT but not in the CYP7B1KO mice. The male reproductive behavior defect in
CYP7B1KO seems to be due to their inability to distinguish olfactory cues from a
behavioral estrus female. CYP7B1KO mice also showed a reduction in androgen
receptor mRNA expression in the olfactory bulb. Our findings suggest a novel role
for the CYP7B1 enzyme in the regulation of male reproductive behaviors.
PMID- 25849731
TI - Determinants of suboptimal breastfeeding practices in Nigeria: evidence from the
2008 demographic and health survey.
AB - BACKGROUND: In Nigeria, suboptimal breastfeeding practices are contributing to
the burden of childhood diseases and mortality. This study identified the
determinants of key suboptimal breastfeeding practices among children 0-23 months
in Nigeria. METHOD: Data on 10,225 children under-24 months were obtained from
the 2008 Nigeria Demographic and Health Survey (NDHS). Socio-economic, health
service and individual factors associated with key breastfeeding indicators
(early initiation of breastfeeding, exclusive breastfeeding, predominant
breastfeeding and bottle feeding) were investigated using multiple logistic
regression analyses. RESULTS: Among infants 0-5 months of age, 14% [95%
confidence Interval (CI): 13%, 15%] were exclusively breastfed and 48% [95% CI:
46, 50%] were predominantly breastfed. Among children aged 0-23 months, 38% [95%
CI 36, 39%] were breastfed within the first hour of birth, and 15% [95% CI: 14,
17%] were bottle-fed. Early initiation of breastfeeding was associated with
higher maternal education, frequent antenatal care (ANC) visits and birth
interval but deliveries at a health facility with caesarean section was
associated with delayed initiation of breastfeeding. Educated mothers, older
mothers and mothers from wealthier households exclusively breastfeed their
babies. The risk for bottle feeding was higher among educated mothers and
fathers, and women from wealthier households including mothers who made frequent
ANC visits. CONCLUSION: Socio-economic and health service factors were associated
with suboptimal breastfeeding practices in Nigeria. To improve the current
breastfeeding practices, breastfeeding initiatives should target all mothers -
particularly low SES mothers - including, national and sub-national health
policies that ensure improved access to maternal health services, and
improvements to baby friendly hospital and community initiatives for mothers.
PMID- 25849732
TI - Trillium tschonoskii steroidal saponins suppress the growth of colorectal Cancer
cells in vitro and in vivo.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Saponins of many herbs are known to possess anti
cancer effect. AIM OF THE STUDY: The present study aimed to investigate the
growth inhibitory effect of Trillium tschonoskii steroidal saponins in a mouse
model of colitis-associated colorectal cancer and a human colorectal cancer cell
line HT-29, and isolate some major constituents and evaluate their anti-tumor
activity. MATERIALS AND METHODS: Forty male ICR mice were administered with 1, 2
dimethyl-hydrazine (DMH) and dextran sodium sulfate (DSS). Ten mice were given no
further treatment, the rest were administered with different doses of TTS (5, 10,
20mg/kg) orally, every three days from the 9th week to the 20th week. RESULTS:
TTS effectively protected ICR mice against DMH/DSS-induced tumorigenesis. The
incidence of tumor development was 90% (9/10) in the mice treated with DMH/DSS,
but that was reduced to 50% (5/10), 40% (4/10), and 20% (2/10), respectively, in
the mice treated with 5%, 10%, and 20% of TTS. Results of Ki-67 staining, TUNEL
assay and caspase-3 activity assay revealed that TTS moderately decreased
abnormal proliferation and increased apoptosis of colonic epithelial cells. It
inhibited the growth and triggered the apoptosis of HT-29 cells, partly through
suppressing mitogen-actived protein kinases (MAPKs) and triggering mitochondrial
mediated apoptotic pathway. Three compounds, namely, Paris saponin VII,
polyphylloside III and Paris saponin VI, were important active compounds in TTS.
CONCLUSION: These data suggest that TTS has a potential role in clinical
prevention and treatment for colorectal cancer.
PMID- 25849733
TI - In vivo estrogenic-like activities of Gouania longipetala Hemsl. (Rhamnaceae)
bark extracts in a post-menopause-like model of ovariectomized Wistar rats.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Gouania longipetala is commonly used in
Cameroonian traditional medicine to manage women fertility and menopausal
complaints. However, despite this use, the estrogenic properties of G.
longipetala have not been studied until now. AIM OF STUDY: The present study was
aimed to assess estrogenic activities of the stem bark aqueous (GLA) and
ethanolic (GLE) extracts of G. longipetala in post-menopause-like model of
ovariectomized (Ovx) Wistar rats. MATERIAL AND METHODS: Animals were either sham
operated or Ovx. 84 days after ovariectomy, animals were divided into seven
groups of five animals and were daily treated for 28 days with distilled water
(10 mL/kg) for group 1, 2% solution of Tween 80 (10 mL/kg) for group 2, estradiol
valerate (1 mg/kg) for group 3, GLA (45 or 180 mg/kg) and GLE (40 or 160 mg/kg)
for groups 4 to 7 respectively. Sham-operated animals daily received distilled
water (10 mL/kg). During the experimental period, the body weight was registered
every week. At the day 29, blood pressure was registered by invasive method while
uterine and vagina morphometry as well as body, uterine and abdominal fat weights
changes were analyzed. Serum levels of total cholesterol, triglycerides, HDL
cholesterol and LDL-cholesterol were determined. Moreover, oxidative stress
markers such as nitrites, reduced glutathione (GSH) and malondialdehyde (MDA)
were measured in homogenized liver and aorta. RESULTS: Compared with the sham
control, vagina and uterine dystrophy and elevated blood pressure were observed
in Ovx rats treated with vehicles. Biochemical parameters showed a significant
increase of total cholesterol, triglycerides, LDL-cholesterol and MDA as well as
a significant decrease of nitrites and GSH in Ovx animals treated with vehicle as
compared to sham group. GLA and GLE displayed estrogen-like effects on vagina and
did not affect uterine wet weight and epithelial height compared with vehicle
groups. Both extracts displayed anti-atherogenic properties by reducing AI, AIP
and LDL-cholesterol level as compared to vehicles groups. GLA and GLE
significantly prevented the increase of MDA induced by ovariectomy as compared to
rats treated with vehicles. CONCLUSION: This study showed that GLA and GLE
exhibited estrogenic effects by providing vaginal lubrication, by modulating
blood pressure and improving lipid profile, oxidative status and endothelial
function and may not have an undesirable influence on the endometrium in
ovariectomized rats.
PMID- 25849734
TI - Yinchenhao decoction in the treatment of cholestasis: A systematic review and
meta-analysis.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Yinchenhao decoction, a well-known Chinese herbal
formula, has been widely used in Chinese Medicine for thousands of years.
However, no systematic review of Yinchenhao decoction in treating cholestasis has
been completed. This study aims to evaluate the efficacy and safety of the
Yinchenhao decoction in treating cholestasis. MATERIALS AND METHODS: The major
databases (PubMed, Embase, Cochrane Library, Chinese Biomedical Database, Wanfang
database, VIP medicine information system and China National Knowledge
Infrastructure) were searched from the databases' inception through November
2014. Randomized controlled trials (RCTs) of Yinchenhao decoction reported in
publications for treatment of cholestasis were extracted by two reviewers. The
RCTs examined included total efficacy rate and biochemical indices including
alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin
(TBIL) and direct bilirubin (DBIL). The Cochrane tool was applied to assess the
risk of bias of the trials. The main outcomes of the trials were analyzed using
Review Manager 5.3 software. The odds ratio (OR) or mean difference (MD) with a
95% confidence interval (CI) was used to measure the effect. RESULTS: Among the
698 studies identified in the literature search, 15 studies involving 1405
subjects with cholestasis were included in the analysis. Yinchenhao decoction
demonstrated efficacy in cholestasis treatment whether in a combined application
or not. Additionally, the decoction significantly reduced the elevated levels of
cholestasis serum markers, such as ALT, AST, TBIL and DBIL, with a significant
difference observed in short and long curative time periods. Remarkably,
Yinchenhao decoction displayed a significant efficacy in treating the long-term
disease. CONCLUSION: No serious adverse event was reported. This meta-analysis
provides evidence that Yinchenhao decoction is an effective and safe treatment
for cholestasis.
PMID- 25849735
TI - Moderately increased albuminuria is an independent risk factor of cardiovascular
events in the general Japanese population under 75 years of age: the Watari
study.
AB - BACKGROUND: Moderately increased albuminuria (formerly called microalbuminuria)
is widely recognized as a predictor of cardiovascular disease. However, it is not
clear whether this observation is applicable to the Asian population, as studies
leading to this conclusion were conducted on Western populations. The aim of this
study was to examine the hypothesis if moderately increased albuminuria could be
an independent predictor of cardiovascular mortality and morbidity in the
Japanese population. METHODS AND RESULTS: The study population consisted of 3093
inhabitants of Watari, Miyagi Prefecture, who participated in an annual health
check-up in 2009. We examined anthropometry, sitting blood pressure, fasting
blood sample, and urine albumin-to-creatinine ratio (UACR). After baseline
assessment, subjects were followed prospectively for up to 60 months. The
incidence of major cardiovascular events (stroke, myocardial infarction,
revascularization, and cardiovascular death) was determined based on death
certificate records or medical claims sent to the National Health Insurance of
Japan. Follow-up was discontinued for those who reached 75 years of age because
they were moved to a different medical insurance system. We observed 57
cardiovascular events during a mean follow-up period of 47.8 months. The
cumulative incidence rate for major cardiovascular events was significantly
higher in patients with moderately increased albuminuria (UACR 30-299 mg/gCr)
than in those with normoalbuminuria (UACR <30 mg/gCr) (6.4% vs. 2.2%, p = 0.0002
by log-rank test). Multivariate Cox proportional hazards analyses have revealed
that moderately increased albuminuria is an independent predictor of
cardiovascular events (HR 2.386, 95% CI: 1.120-4.390). CONCLUSIONS: Moderately
increased albuminuria is an independent predictor of cardiovascular events in the
general Japanese population under 75 years of age.
PMID- 25849736
TI - Correction: evaluation of intradural stimulation efficiency and selectivity in a
computational model of spinal cord stimulation.
PMID- 25849737
TI - Network Modularity is essential for evolution of cooperation under uncertainty.
AB - Cooperative behavior, which pervades nature, can be significantly enhanced when
agents interact in a structured rather than random way; however, the key
structural factors that affect cooperation are not well understood. Moreover, the
role structure plays with cooperation has largely been studied through observing
overall cooperation rather than the underlying components that together shape
cooperative behavior. In this paper we address these two problems by first
applying evolutionary games to a wide range of networks, where agents play the
Prisoner's Dilemma with a three-component stochastic strategy, and then analyzing
agent-based simulation results using principal component analysis. With these
methods we study the evolution of trust, reciprocity and forgiveness as a
function of several structural parameters. This work demonstrates that community
structure, represented by network modularity, among all the tested structural
parameters, has the most significant impact on the emergence of cooperative
behavior, with forgiveness showing the largest sensitivity to community
structure. We also show that increased community structure reduces the dispersion
of trust and forgiveness, thereby reducing the network-level uncertainties for
these two components; graph transitivity and degree also significantly influence
the evolutionary dynamics of the population and the diversity of strategies at
equilibrium.
PMID- 25849738
TI - Controlling band alignments by artificial interface dipoles at perovskite
heterointerfaces.
AB - The concept 'the interface is the device' is embodied in a wide variety of
interfacial electronic phenomena and associated applications in oxide materials,
ranging from catalysts and clean energy systems to emerging multifunctional
devices. Many device properties are defined by the band alignment, which is often
influenced by interface dipoles. On the other hand, the ability to purposefully
create and control interface dipoles is a relatively unexplored degree of freedom
for perovskite oxides, which should be particularly effective for such ionic
materials. Here we demonstrate tuning the band alignment in perovskite metal
semiconductor heterojunctions over a broad range of 1.7 eV. This is achieved by
the insertion of positive or negative charges at the interface, and the resultant
dipole formed by the induced screening charge. This approach can be broadly used
in applications where decoupling the band alignment from the constituent work
functions and electron affinities can enhance device functionality.
PMID- 25849739
TI - Synthesis, Characterization, and Sunlight Mediated Photocatalytic Activity of CuO
Coated ZnO for the Removal of Nitrophenols.
AB - CuO@ZnO core-shell catalysts, coated by varying the CuO layer density ranging
from 0.5% to 10%, were synthesized with the aim to enhance the photocatalytic
activity of ZnO in sunlight and control its photocorrosion. Initially, the Cu(2+)
ions were impregnated on presynthesized ZnO by wet impregnation and finally
converted to CuO layers by calcination. The optical and structural
characterization of the synthesized powders was performed by DRS, PL, Raman
spectroscopy, and XRD analysis, respectively. The homogeneity of the coated
layers was explored by FESEM. The photocatalytic activity of CuO coated ZnO was
investigated for the degradation of mononitrophenols (2-, 3-, and 4-nitrophenol)
and dinitrophenols (2,4-, 2,5-, and 2,6-dinitrophenol) in the exposure of the
complete spectrum and visible region (420-800 nm) of sunlight. The effect of the
increasing density coated layers of CuO on photocatalytic activity was evaluated
for the degradation of 4-NP. Compared to pristine ZnO, a substantial increase in
the degradation/mineralization ability was observable for the catalysts coated
with 0.5% and 1% CuO, whereas a detrimental effect was noticed for higher coating
density. Prior to photocatalytic studies, as evaluated by cyclic voltammetry
(CV), compared to pure ZnO, a significant suppression of photocorrosion was
noticed, under illumination, for catalysts coated with lower CuO coating. The
progress of the photocatalytic degradation process was monitored by HPLC while
the mineralization ability of the synthesized catalysts was estimated by TOC. The
estimation of the released ions and their further interaction with the excited
states and the reactive oxygen was monitored by ion chromatography (IC).
PMID- 25849740
TI - Lpr-induced systemic autoimmunity is unaffected by mast cell deficiency.
AB - The function of mast cells in allergic and organ-specific autoimmune responses is
highly controversial. In the current study, we aimed to dissect the role of mast
cells in systemic autoimmunity in the B6(lpr/lpr) mouse, a spontaneous model of
systemic lupus erythematosus. B6(lpr/lpr) mice were interbred with C57Bl/6-Kit(W
sh/W-sh) (Wsh) mice, resulting in mast cell deficiency. The offspring from this
cross (Lpr/Wsh mice) developed symptoms of lupus of the same severity as
B6(lpr/lpr) mice. Loss of mast cells on the Lpr background did not alter
autoantibody production, proteinuria, the composition of T and B cell populations
or autoimmune pathology. Reduced c-Kit expression did drive expanded splenomegaly
and impeded interleukin-4 production by CD4(+) cells, suggesting minor functions
for mast cells. In general, we conclude that mast cell deficiency and c-Kit
deficiency do not play a role in the pathogenesis of lupus in B6(lpr/lpr) mice.
PMID- 25849741
TI - Quantitative analysis of the TNF-alpha-induced phosphoproteome reveals AEG
1/MTDH/LYRIC as an IKKbeta substrate.
AB - The inhibitor of the nuclear factor-kappaB (IkappaB) kinase (IKK) complex is a
key regulator of the canonical NF-kappaB signalling cascade and is crucial for
fundamental cellular functions, including stress and immune responses. The
majority of IKK complex functions are attributed to NF-kappaB activation;
however, there is increasing evidence for NF-kappaB pathway-independent
signalling. Here we combine quantitative mass spectrometry with random forest
bioinformatics to dissect the TNF-alpha-IKKbeta-induced phosphoproteome in MCF-7
breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of
which ~1% are regulated up on TNF-alpha stimulation. We identify various
potential novel IKKbeta substrates including kinases and regulators of cellular
trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is
directly phosphorylated by IKKbeta on serine 298. We provide evidence that
IKKbeta-mediated AEG-1 phosphorylation is essential for IkappaBalpha degradation
as well as NF-kappaB-dependent gene expression and cell proliferation, which
correlate with cancer patient survival in vivo.
PMID- 25849742
TI - Defective pericyte recruitment of villous stromal vessels as the possible
etiologic cause of hydropic change in complete hydatidiform mole.
AB - The pathogenetic mechanism underlying the hydropic change in complete
hydatidiform moles (CHMs) is poorly understood. A growing body of data suggests
that pericytes play a role in vascular maturation. Since maturation of villous
stromal vessels in CHMs is markedly impaired at early stages, we postulated that
a defect in pericytes around stromal vessels in chorionic villi might cause
vascular immaturity and subsequent hydropic change. To investigate this, we
examined several markers of pericytes, namely, alpha-smooth muscle actin (alpha
SMA), platelet-derived growth factor receptor-beta (PDGFR-beta), and desmin, in
61 normally developing placentas and 41 CHMs with gestational ages of 4-12 weeks.
The ultrastructure of villous stromal vessels was also examined. Mature blood
vessels from normal placentas show patent vascular lumens and formed
hematopoietic components in the villous stroma. alpha-SMA and PDGFR-beta
expression in the villous stroma gradually increased and extended from the
chorionic plate to peripheral villous branches. The labeled cells formed a
reticular network in the villous stroma and, after week 7, encircled villous
stromal vessels. In comparison, alpha-SMA and PDGFR-beta expression in the
villous stroma and stromal vessels of CHMs was significantly lower (p<0.05).
Ultrastructurally, endothelial cells in villous stromal vessels in normal
placentas were consistently attached by pericytes after week 7 when the vessels
formed distinct lumen, whereas the villous stromal vessels in CHMs consisted of
linear chains of endothelial cells, often disclosing primitive clefts without
hematopoietic cells inside, and neither pericytes nor basal lamina surrounded the
endothelial cells at any gestational age studied. This suggests that pericytes
recruitment around villous stromal vessels is defective in CHMs and links to the
persistent vascular immaturity of the villous stroma in CHMs, which in turns
leads to hydropic villi.
PMID- 25849743
TI - Iron metallodrugs: stability, redox activity and toxicity against Artemia salina.
AB - Iron metallodrugs comprise mineral supplements, anti-hypertensive agents and,
more recently, magnetic nanomaterials, with both therapeutic and diagnostic
roles. As biologically-active metal compounds, concern has been raised regarding
the impact of these compounds when emitted to the environment and associated
ecotoxicological effects for the fauna. In this work we assessed the relative
stability of several iron compounds (supplements based on glucoheptonate, dextran
or glycinate, as well as 3,5,5-trimethylhexanoyl (TMH) derivatives of ferrocene)
against high affinity models of biological binding, calcein and aprotransferrin,
via a fluorimetric method. Also, the redox-activity of each compound was
determined in a physiologically relevant medium. Toxicity toward Artemia salina
at different developmental stages was measured, as well as the amount of lipid
peroxidation. Our results show that polymer-coated iron metallodrugs are stable,
non-redox-active and non-toxic at the concentrations studied (up to 300 uM).
However, TMH derivatives of ferrocene were less stable and more redox-active than
the parent compound, and TMH-ferrocene displayed toxicity and lipid peroxidation
to A. salina, unlike the other compounds. Our results indicate that iron
metallodrugs based on polymer coating do not present direct toxicity at low
levels of emission; however other iron species (eg. metallocenes), may be
deleterious for aquatic organisms. We suggest that ecotoxicity depends more on
metal speciation than on the total amount of metal present in the metallodrugs.
Future studies with discarded metallodrugs should consider the chemical
speciation of the metal present in the composition of the drug.
PMID- 25849744
TI - Improved Escherichia coli Bactofection and Cytotoxicity by Heterologous
Expression of Bacteriophage PhiX174 Lysis Gene E.
AB - Bactofection offers a gene delivery option particularly useful in the context of
immune modulation. The bacterial host naturally attracts recognition and cellular
uptake by antigen presenting cells (APCs) as the initial step in triggering an
immune response. Moreover, depending on the bacterial vector, molecular biology
tools are available to influence and/or overcome additional steps and barriers to
effective antigen presentation. In this work, molecular engineering was applied
using Escherichia coli as a bactofection vector. In particular, the bacteriophage
PhiX174 lysis E (LyE) gene was designed for variable expression across strains
containing different levels of lysteriolysin O (LLO). The objective was to
generate a bacterial vector with improved attenuation and delivery
characteristics. The resulting strains exhibited enhanced gene and protein
release and inducible cellular death. In addition, the new vectors demonstrated
improved gene delivery and cytotoxicity profiles to RAW264.7 macrophage APCs.
PMID- 25849746
TI - Pd(II)-Catalyzed Pyridine N-Oxides Directed Arylation of Unactivated Csp(3)-H
Bonds.
AB - A novel Pd(II)-catalyzed pyridine N-oxide directed remote arylation of
unactivated Csp(3)-H bonds in aliphatic amides with aryl iodides has been
developed. This protocol allows installing various aryl groups at the beta- or
gamma-Csp(3) atom of alkyl carboxylic acid amides. The key palladabicyclic
intermediate of this transformation has been identified by HR-MS and (1)H NMR
method.
PMID- 25849745
TI - Inhibition of iNOS as a novel effective targeted therapy against triple-negative
breast cancer.
AB - INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive form of
breast cancer with no effective targeted therapy. Inducible nitric oxide synthase
(iNOS) is associated with poor survival in patients with breast cancer by
increasing tumor aggressiveness. This work aimed to investigate the potential of
iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition
of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor
initiation and metastasis through modulation of epithelial-mesenchymal transition
(EMT)-inducing factors. METHODS: iNOS protein levels were determined in 83 human
TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere
forming efficiency, migration, and EMT transcription factors were assessed in
vitro after iNOS inhibition. Endogenous iNOS targeting was evaluated as a
potential therapy in TNBC mouse models. RESULTS: High endogenous iNOS expression
was associated with worse prognosis in patients with TNBC by gene expression as
well as immunohistochemical analysis. Selective iNOS (1400 W) and pan-NOS (L-NMMA
and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self
renewal, and cell migration in vitro, together with inhibition of EMT
transcription factors (Snail, Slug, Twist1, and Zeb1). Impairment of hypoxia
inducible factor 1alpha, endoplasmic reticulum stress (IRE1alpha/XBP1), and the
crosstalk between activating transcription factor 3/activating transcription
factor 4 and transforming growth factor beta was observed. iNOS inhibition
significantly reduced tumor growth, the number of lung metastases, tumor
initiation, and self-renewal. CONCLUSIONS: Considering the effectiveness of L
NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a
targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA,
which has been extensively investigated for cardiogenic shock as an anti-cancer
therapeutic.
PMID- 25849748
TI - The quantum theory of rural practice.
PMID- 25849747
TI - Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms
Underlying the Significant Association.
AB - Epidemiology and experimental studies provide an overwhelming support of the
notion that diets high in red or processed meat accompany an elevated risk of
developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma
(CRC). The underlying mechanisms are disputed; thus several hypotheses have been
proposed. A large body of reports converges, however, on haem and nitrosyl haem
as major contributors to the CRC development, presumably acting through various
mechanisms. Apart from a potentially higher intestinal mutagenic load among
consumers on a diet rich in red/processed meat, other mechanisms involving subtle
interference with colorectal stem/progenitor cell survival or maturation are
likewise at play. From an overarching perspective, suggested candidate mechanisms
for red/processed meat-induced CRC appear as three partly overlapping tenets: (i)
increased N-nitrosation/oxidative load leading to DNA adducts and lipid
peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the
epithelium through haem or food-derived metabolites that either act directly or
subsequent to conversion, and (iii) higher inflammatory response, which may
trigger a wide cascade of pro-malignant processes. In this review, we summarize
and discuss major findings of the area in the context of potentially pertinent
mechanisms underlying the above-mentioned association between consumption of
red/processed meat and increased risk of developing CRC.
PMID- 25849750
TI - President's message. Enhanced surgical services.
PMID- 25849752
TI - Nurse-led diabetes management in remote locations.
AB - INTRODUCTION: Nurse-led diabetes management has been shown to be effective in
urban and regional general practice. We sought to test the feasibility of
providing a nurse-led annual cycle of diabetes care in a remote location and to
explore the factors that patients indicated were important in diabetes self
management. METHODS: We conducted a pilot study in 3 locations: 1 town and 2
small townships in remote Australia. A chronic disease nurse (CDN) visited each
patient over the course of a year. We examined patient clinical outcomes and
interview data. We estimated the cost per hour of the CDN's time, including
travel time, per 1% drop in glycated hemoglobin (HbA1C). RESULTS: A total of 21
patients participated in the pilot study. Clinical findings showed significant
reductions in HbA1C levels after the nurse-led intervention. Patients reported
that they trusted the nurse and thought her advice was pitched at their level.
Patients were motivated through a process that included emotional response,
change identity and acceptance. The estimated cost in CDN hours per 1% drop in
HbA1C level was A$242.95 (Can$237.60). CONCLUSION: Nurse-led diabetes care
motivated patients to manage their diabetes and resulted in a significant
improvement in diabetes management in this remote setting.
PMID- 25849753
TI - Vancomycin use in a rural hospital: a 3-year retrospective study.
AB - INTRODUCTION: Urban centres often perform audits of vancomycin use as they face
outbreaks of resistant organisms. We undertook this study to understand the
indications and duration of intravenous vancomycin in a rural setting. METHODS:
We conducted a retrospective chart audit for all patients who received
intravenous vancomycin over a 3-year period at a rural hospital in northwestern
Ontario. RESULTS: Vancomycin was used intravenously in 180 patients during the
study period. It was used for short courses (median 3 d), and serum levels were
below target 72% of the time. CONCLUSION: High rates of invasive methicillin
resistant Staphylococcus aureus bacteremia and limited antibiotic choices in the
field likely contributed to short courses of this antibiotic. Further study on
clinical severity and antibiotic choice is needed. Additionally, weight-based
dosing may result in target serum levels being achieved more frequently.
PMID- 25849754
TI - Country cardiograms case 53.
PMID- 25849755
TI - The occasional posterior hip dislocation reduction.
PMID- 25849757
TI - From the T-dot to the Rock: my journey in rural family medicine.
PMID- 25849758
TI - Biology, ecology and distribution of the tick, Haemaphysalis longicornis Neumann
(Acari: Ixodidae) in New Zealand.
AB - Haemaphysalis longicornis is the only tick in New Zealand that infests livestock.
Throughout its range H. longicornis is exposed to and exhibits tolerance to a
wide range of environmental conditions, although it flourishes more in moist,
warm-temperate environments. This review examines aspects of the biology,
physiology and ecology of H. longicornis that determine its distribution and
seasonal activity in New Zealand, based on laboratory and field studies. Examples
are also drawn from studies outside New Zealand for comparative purposes,
especially in the context of seasonal activity as seen in less temperate
latitudes. The tick is able to withstand a wide range of temperature, from its
developmental threshold of ~12 degrees C to nearly 40 degrees C at its lethal
limit, but its tolerance of dehydration is less wide, especially in the larva and
adult, the former especially being the stage that largely determines suitable
biotopes for the tick and its present distributional limits. The importance of H.
longicornis to the New Zealand livestock industry has recently increased through
the establishment and spread of Theileria orientalis Ikeda among dairy and beef
cattle, although the tick has always posed production-limiting problems for
cattle, deer and to a lesser extent, sheep. The tick's role as a vector of
theileriosis and how aspects of the tick's biology affect the spread and
maintenance of this disease are discussed. It is proposed that, of available
wildlife hosts, the brown hare with its wide-ranging habits, is an important
disseminator of ticks. Currently control of ticks is difficult partly because of
their wide host range, overlapping activity periods of stadia, and also because
the greater part of their annual cycle is spent on pasture. This means that
acaricides alone do not satisfactorily reduce tick populations or provide
comprehensive protection to stock, so integrated management combining pasture
management with good husbandry and chemical prophylaxis is advocated.
PMID- 25849759
TI - Fixational saccades during grating detection and discrimination.
AB - We investigated the patterns of fixational saccades in human observers performing
two classical perceptual tasks: grating detection and discrimination. First,
participants were asked to detect a vertical or tilted grating with one of three
spatial frequencies and one of four luminance contrast levels. In the second
experiment, participants had to discriminate the spatial frequency of two supra
threshold gratings. The gratings were always embedded in additive, high- or low
contrast pink noise. We observed that the patterns of fixational saccades were
highly idiosyncratic among participants. Moreover, during the grating detection
task, the amplitude and the number of saccades were inversely correlated with
stimulus visibility. We did not find a systematic relationship between saccade
parameters and grating frequency, apart from a slight decrease of saccade
amplitude during grating discrimination with higher spatial frequencies. No
consistent changes in the number and amplitude of fixational saccades with
performance accuracy were reported. Surprisingly, during grating detection,
saccade number and amplitude were similar in grating-with-noise and noise-only
displays. Grating orientation did not affect substantially saccade direction in
either task. The results challenge the idea that, when analyzing low-level
spatial properties of visual stimuli, fixational saccades can be adapted in order
to extract task-relevant information optimally. Rather, saccadic patterns seem to
be overall modulated by task context, stimulus visibility and individual
variability.
PMID- 25849760
TI - Theoretical investigation on the restoring step of the carbonic anhydrase
catalytic cycle for natural and promiscuous substrates.
AB - In the present study steered molecular dynamics simulations were applied to
investigate the unbinding process of the complex of human carbonic anhydrase with
the natural HCO3(-) and promiscuous H2NCOHN(-) products. This process is crucial
for restoring the catalytic cycle of the enzyme. This investigation set out to
give further insights on the release mechanism involved in the case of the
promiscuous product believed suicide inhibitor for the hCAII against the natural
final product. In particular, on the basis of the NPT molecular dynamics
simulations performed on the bicarbonate, the penta-coordinated complex with the
water is observed, while in the case of the ureate the same event does not take
place. At this purpose the calculated potential of mean force based on the
steered molecular dynamics (SMD) simulations shed light on an optimal pathway for
the releasing of the products.
PMID- 25849761
TI - Functional characterization of CYP107W1 from Streptomyces avermitilis and
biosynthesis of macrolide oligomycin A.
AB - Streptomyces avermitilis contains 33 cytochrome P450 genes in its genome, many of
which play important roles in the biosynthesis process of antimicrobial agents.
Here, we characterized the biochemical function and structure of CYP107W1 from S.
avermitilis, which is responsible for the 12-hydroxylation reaction of oligomycin
C. CYP107W1 was expressed and purified from Escherichia coli. Purified proteins
exhibited the typical CO-binding spectrum of P450. Interaction of oligomycin C
and oligomycin A (12-hydroxylated oligomycin C) with purified CYP107W1 resulted
in a type I binding with Kd values of 14.4 +/- 0.7 MUM and 2.0 +/- 0.1 MUM,
respectively. LC-mass spectrometry analysis showed that CYP107W1 produced
oligomycin A by regioselectively hydroxylating C12 of oligomycin C. Steady-state
kinetic analysis yielded a kcat value of 0.2 min(-1) and a Km value of 18 MUM.
The crystal structure of CYP107W1 was determined at 2.1 A resolution. The overall
P450 folding conformations are well conserved, and the open access binding pocket
for the large macrolide oligomycin C was observed above the distal side of heme.
This study of CYP107W1 can help a better understanding of clinically important
P450 enzymes as well as their optimization and engineering for synthesizing novel
antibacterial agents and other pharmaceutically important compounds.
PMID- 25849763
TI - Amilorides bind to the quinone binding pocket of bovine mitochondrial complex I.
AB - Amilorides, well-known inhibitors of Na(+)/H(+) antiporters, were previously
shown to inhibit bacterial and mitochondrial NADH-quinone oxidoreductase (complex
I) but were markedly less active for complex I. Because membrane subunits ND2,
ND4, and ND5 of bovine complex I are homologous to Na(+)/H(+) antiporters,
amilorides have been thought to bind to any or all of the antiporter-like
subunits; however, there is currently no direct experimental evidence that
supports this notion. To identify the binding site of amilorides in bovine
complex I, we synthesized two photoreactive amilorides (PRA1 and PRA2), which
have a photoreactive azido (-N3) group and terminal alkyne (-C=CH) group at the
opposite ends of the molecules, respectively, and conducted photoaffinity
labeling with bovine heart submitochondrial particles. The terminal alkyne group
allows various molecular tags to covalently attach to it via Cu(+)-catalyzed
click chemistry, thereby allowing purification and/or detection of the labeled
peptides. Proteomic analyses revealed that PRA1 and PRA2 label none of the
antiporter-like subunits; they specifically label the accessory subunit B14.5a
and core subunit 49 kDa (N-terminal region of Thr25-Glu115), respectively.
Suppressive effects of ordinary inhibitors (bullatacin, fenpyroximate, and
quinazoline), which bind to the putative quinone binding pocket, on labeling were
fairly different between the B14.5a and 49 kDa subunits probably because the
binding positions of the three inhibitors differ within the pocket. The results
of this study clearly demonstrate that amilorides inhibit complex I activity by
occupying the quinone binding pocket rather than directly blocking translocation
of protons through the antiporter-like subunits (ND2, ND4, and ND5). The
accessory subunit B14.5a may be located adjacent to the N-terminal region of the
49 kDa subunits. The structural features of the quinone binding pocket in bovine
complex I were discussed on the basis of these results.
PMID- 25849762
TI - Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase
PFKFB3.
AB - A weak screening hit with suboptimal physicochemical properties was optimized
against PFKFB3 kinase using critical structure-guided insights. The resulting
compounds demonstrated high selectivity over related PFKFB isoforms and
modulation of the target in a cellular context. A selected example demonstrated
exposure in animals following oral dosing. Examples from this series may serve as
useful probes to understand the emerging biology of this metabolic target.
PMID- 25849765
TI - Absence of effects on the rat sperm quality after subacute exposure to low doses
of fungicide prochloraz.
AB - Prochloraz (PCZ) is a fungicide and androgen-receptor antagonist used worldwide
in horticulture and agriculture. Pre- and perinatal exposure to this pesticide
during sexual differentiation is deleterious for male offspring. Since data on
the effects of PCZ on epididymal functions are scarce, and because sperm
maturation occurs in this organ, the present investigation aimed to determine
whether low PCZ doses administered to rats during the phase of sperm transit
through the epididymis might affect the morphophysiology of this organ and sperm
quality. Adult male Wistar rats were assigned to 4 different groups: 0 (control,
vehicle) or 10, 15, or 30 mg/kg bw/d PCZ diluted in corn oil administered orally
for 4 consecutive days. Morphofunctional parameters of the male reproductive
tract, hormone concentrations, sperm evaluations, and fertility and
histopathologic analysis of testis and epididymis were assessed. There were no
statistically significant differences between treated and control groups in
relation to all evaluated parameters. Data demonstrated show that PCZ exposure
for a brief 4-d exposure and low doses did not produce reproductive toxicity or
compromise sperm quality in adult rats.
PMID- 25849764
TI - AtEAF1 is a potential platform protein for Arabidopsis NuA4 acetyltransferase
complex.
AB - BACKGROUND: Histone acetyltransferase complex NuA4 and histone variant exchanging
complex SWR1 are two chromatin modifying complexes which act cooperatively in
yeast and share some intriguing structural similarities. Protein subunits of NuA4
and SWR1-C are highly conserved across eukaryotes, but form different
multiprotein arrangements. For example, the human TIP60-p400 complex consists of
homologues of both yeast NuA4 and SWR1-C subunits, combining subunits necessary
for histone acetylation and histone variant exchange. It is currently not known
what protein complexes are formed by the plant homologues of NuA4 and SWR1-C
subunits. RESULTS: We report on the identification and molecular characterization
of AtEAF1, a new subunit of Arabidopsis NuA4 complex which shows many
similarities to the platform protein of the yeast NuA4 complex. AtEAF1 copurifies
with Arabidopsis homologues of NuA4 and SWR1-C subunits ARP4 and SWC4 and
interacts physically with AtYAF9A and AtYAF9B, homologues of the YAF9 subunit.
Plants carrying a T-DNA insertion in one of the genes encoding AtEAF1 showed
decreased FLC expression and early flowering, similarly to Atyaf9 mutants.
Chromatin immunoprecipitation analyses of the single mutant Ateaf1b-2 and
artificial miRNA knock-down Ateaf1 lines showed decreased levels of H4K5
acetylation in the promoter regions of major flowering regulator genes, further
supporting the role of AtEAF1 as a subunit of the plant NuA4 complex.
CONCLUSIONS: Growing evidence suggests that the molecular functions of the NuA4
and SWR1 complexes are conserved in plants and contribute significantly to plant
development and physiology. Our work provides evidence for the existence of a
yeast-like EAF1 platform protein in A. thaliana, filling an important gap in the
knowledge about the subunit organization of the plant NuA4 complex.
PMID- 25849766
TI - Benzophenone-1 and nonylphenol stimulated MCF-7 breast cancer growth by
regulating cell cycle and metastasis-related genes via an estrogen receptor alpha
dependent pathway.
AB - Endocrine-disrupting chemicals (EDC) are defined as environmental compounds that
produce adverse health manifestations in mammals by disrupting the endocrine
system. Benzophenone-1 (2,4-dihydroxybenzophenone, BP1) and nonylphenol (NP),
which are discharged from numerous industrial products, are known EDC. The aim of
this study was to examine the effects of BP1 and NP on proliferation and
metastasis of MCF-7 human breast cancer cells expressing estrogen receptors (ER).
Treatment with BP1 (10-5-10-7 M) and NP (10-6-10-7 M) promoted proliferation of
MCF-7 cells similar to the positive control 17 -beta-estradiol (E2). When ICI
182,780, an ER antagonist, was co-incubated with E2, BP1, or NP, proliferation of
MCF-7 cells returned to the level of a control. Addition of BP1 or NP markedly
induced migration of MCF-7 cells similar to E2. To elucidate the underlying
molecular mechanisms produced by these EDC, alterations in transcriptional and
translational levels of proliferation and metastasis-related markers, including
cyclin D1, p21, and cathepsin D, were determined. Data showed increase in
expression of cyclin D1 and cathepsin D and decrease in p21 at both
transcriptional and translational levels. However, BP1- or NP-induced alterations
of these genes were blocked by ICI 182,780, suggesting that changes in expression
of these genes may be regulated by an ERalpha-dependent pathway. In conclusion,
BP1 and NP may accelerate growth of MCF-7 breast cancer cells by regulating cell
cycle-related genes and promote cancer metastasis through amplification of
cathepsin D.
PMID- 25849767
TI - Fine particulate air pollution and outpatient department visits for headache in
Taipei, Taiwan.
AB - This study was undertaken to determine whether there was an association between
fine particle matter (PM(2.5)) levels and daily outpatient department visits
(OPD) for headaches in Taipei, Taiwan. Daily OPD visits for headaches and ambient
air pollution data for Taipei were obtained for the period 2006-2011. The
relative risk of visits for OPD headaches was estimated using a case-crossover
approach, controlling for weather variables, day of the week, seasonality, and
long-term time trends. For the single-pollutant model (without adjustment for
other pollutants), increased OPD visits for headaches were significantly
associated with levels of PM(2.5) both on warm days (>23 degrees C) and cool days
(<23 degrees C), with an interquartile range rise associated with a 12% (95% CI =
10-14%) and 3% (95% CI = 1-5%) elevation in OPD visits for headaches,
respectively. In the two-pollutant models, PM(2.5) remained significant after
inclusion of sulfur dioxide (SO2) or ozone (O3) on both warm and cool days. This
study provides evidence that higher levels of PM(2.5) increase the risk of OPD
visits for headaches in Taipei, Taiwan.
PMID- 25849768
TI - Altered expression levels of neurodevelopmental proteins in fetal brains of BTBR
T+tf/J mice with autism-like behavioral characteristics.
AB - Autism is a brain developmental disorder with characteristics of social
interaction defects, language and communication dysfunction, and repetitive
behavior. Occurrence of autism is continuously increasing, but the cause of
autism is not clearly defined. Genetic linkage or environmental factors were
proposed as sources for pathogenesis of autism. BTBR T+tf/J (BTBR) mice were
reported as an appropriate animal model for autism investigation because of their
similarities in behavioral abnormalities with human autistic subjects. The aim of
this study was to evaluate expression levels of proteins involved with brain
development at fetal stage of BTBR mice. FVB/NJ mice were used as a control
strain because of their social behaviors. Level of fetal brain immunoglobulin
(Ig) G deposit was also evaluated. Fetal brains were obtained at d 18 of
gestational period. Thirty-one and 27 fetuses were obtained from 3 pregnant BTBR
and FVB dams, respectively. The level of glial fibrillary acidic protein
expression was significantly lower in fetal brains of BTBR than FVB/NJ mice.
Expression of brain-derived neurotrophic factor and myelin basic protein was
significantly more upregulated in BTBR than in FVB/NJ mice. No significant
difference was obtained for nerve growth factor between the two strains. Levels
of IgG isotypes deposited in fetal brain of BTBR mice were significantly higher
than in FVB mice except for IgG1. Overall, these results suggest that prenatal
alterations in expression of various fetal brain proteins may be implicated in
aberrant behavioral characteristics of BTBR mice.
PMID- 25849769
TI - The air quality health index and emergency department visits for urticaria in
Windsor, Canada.
AB - Ambient air pollution exposure has been associated with several health
conditions, limited not only to respiratory and cardiovascular systems but also
to cutaneous tissues. However, few epidemiological studies examined pollution
exposure on skin problems. Basically, the common mechanism by which pollution may
affect skin physiology is by induction of oxidative stress and inflammation.
Urticaria is among the skin pathologies that have been associated with pollution.
Based on the combined effects of three ambient air pollutants, ozone (O3),
nitrogen dioxide (NO2), and fine particulate matter (PM) with a median
aerodynamic diameter of less than 2.5 MUm (PM(2.5)), on mortality, the Air
Quality Health Index (AQHI) in Canada was developed. The aim of this study was to
examine the associations of short-term changes in AQHI with emergency department
(ED) visits for urticaria in Windsor-area hospitals in Canada. Diagnosed ED
visits were retrieved from the National Ambulatory Care Reporting System (NACRS).
A time-stratified case-crossover design was applied to 2905 ED visits (males =
1215; females = 1690) for urticaria from April 2004 through December 2010. Odds
ratios (OR) and their corresponding 95% confidence intervals (95%CI) for ED
visits associated with increase by one unit of risk index were calculated
employing conditional logistic regression. Positive and significant results were
observed between AQHI levels and OR for ED visits for urticaria in Windsor for
lags 2 and 3 days. A distributed lag nonlinear model technique was applied to
daily counts of ED visits for lags 0 to 10 and significant results were obtained
from lag 2 to lag 5 and for lag 9. These findings demonstrated associations
between ambient air pollution and urticarial confirming that air pollution
affects skin conditions.
PMID- 25849770
TI - Hematological and hepatic alterations in Brazilian population heavily exposed to
organochlorine pesticides.
AB - The aim of this study was to investigate the frequency of hematological and
hepatic alterations and possible association with serum levels of beta
hexachlorocyclohexane (beta-HCH), p,p'-DDE, and hexachlorobenzene (HCB) among
residents in an area heavily contaminated with organochlorine (OC) pesticides. A
cross-sectional study was conducted in 415 male and 432 female residents aged >14
years. Serum samples were collected and analyzed for OC pesticides concentrations
and biochemical parameters. Frequencies of hematological and hepatic alterations
were calculated for each gender. Association between beta-HCH, p,p'-DDE (1,1
dichloro-2,2-bis(p-chlorophenyl) ethylene), and HCB levels and presence of
alterations was determined by logistic regression stratified by gender and
controlling for confounders. Highest frequencies were observed for eosinophilia
(23% men and 18% women), low hemoglobin (12% men and 15% women), and low
erythrocyte count (12% men). High levels of bilirubin, glutamic-oxaloacetic
transaminase (GOT), and glutamic-pyruvic transaminase (GPT) were observed,
respectively, in 10, 11, and 12% of men and <10% of women. Gamma-glutamyl
transferase (GGT) was elevated in 26 and 25% of males and females, respectively.
Multivariate analysis revealed associations between eosinophilia and beta-HCH in
men (OR = 1.06, 95%CI = 1.01-1.12) and women (OR = 1.05, 96%CI = 0.99-1.11), p,p'
DDE in men (OR = 1.03, 95%CI = 0.99-1.06) and women (OR = 1.02, 95%CI = 0.99
1.06), and HCB in women (OR = 1.54, 95%IC = 0.85-4.45). Beta-HCH was found to be
associated with increased risk of elevated bilirubin in females (OR = 1.18, 95%CI
= 1.07-1.29) and males (OR = 4.21, 95%CI = 1.87-9.47 for fourth vs. first
quintile). Thus, OC pesticides may exert adverse effects on hematopoietic tissue
and liver in populations chronically exposed to high levels of these compounds.
PMID- 25849772
TI - The implications of probability matching for clinician response to vital sign
alarms: a theoretical study of alarm fatigue.
AB - Alarm fatigue has been recognised as a significant health technology safety risk.
'Probability matching', in which clinicians respond to the alarm at a rate
identical to the perceived reliability of the alarm, has been postulated as a
model to explain alarm fatigue. In this article, we quantitatively explore the
implications of probability matching for systolic blood pressure alarms. We find
that probability matching could have a profound effect on clinician response to
the alarm, with a response rate of only 8.6% when the alarm threshold is 90 mm Hg
and the optimal threshold for a systolic blood pressure alarm would only be 77 mm
Hg. We use the mathematical framework to assess a mitigation strategy when
clinicians have a limit to the capacity to respond. We find that a tiered alarm
in which clinicians receive information on the severity of vital sign
perturbation significantly improves the opportunity to rescue patients.
Practitioner Summary: Using a theoretical model, we predict that probability
matching, a postulated model of clinician behaviour, can result in a profound
decrease in clinician response to alarms for decreased blood pressure. A
mitigating strategy is to create alarms that convey information on the degree of
vital sign perturbation.
PMID- 25849771
TI - DNA methylation and transcriptomic changes in response to different lights and
stresses in 7B-1 male-sterile tomato.
AB - We reported earlier that 7B-1 mutant in tomato (Solanum lycopersicum L., cv.
Rutgers), an ABA overproducer, is defective in blue light (B) signaling leading
to B-specific resistance to abiotic and biotic stresses. Using a methylation
sensitive amplified polymorphism (MSAP) assay, a number of genes were identified,
which were differentially methylated between 7B-1 and its wild type (WT)
seedlings in white (W), blue (B), red (R) lights and dark (D) or in response to
exogenous ABA and mannitol-induced stresses. The genomic methylation level was
almost similar in different lights between 7B-1 and WT seedlings, while
significant differences were observed in response to stresses in D, but not B.
Using a cDNA-AFLP assay, several transcripts were identified, which were
differentially regulated between 7B-1 and WT by B or D or in response to
stresses. Blue light receptors cryptochrome 1 and 2 (CRY1 and CRY2) and
phototropin 1 and 2 (PHOT1 and PHOT2) were not affected by the 7B-1 mutation at
the transcriptional level, instead the mutation had likely affected downstream
components of the light signaling pathway. 5-azacytidine (5-azaC) induced DNA
hypomethylation, inhibited stem elongation and differentially regulated the
expression of a number of genes in 7B-1. In addition, it was shown that mir167
and mir390 were tightly linked to auxin signaling pathway in 5-azaC-treated 7B-1
seedlings via the regulation of auxin-response factor (ARF) transcripts. Our data
showed that DNA methylation remodeling is an active epigenetic response to
different lights and stresses in 7B-1 and WT, and highlighted the differences in
epigenetic and transcriptional regulation of light and stress responses between
7B-1 and WT. Furthermore, it shed lights on the crosstalk between DNA
hypomethylation and miRNA regulation of ARFs expression. This information could
also be used as a benchmark for future studies of male-sterility in other crops.
PMID- 25849774
TI - Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem
cell pool.
AB - Tissue homeostasis is achieved through a balance of cell production (growth) and
elimination (regression). In contrast to tissue growth, the cells and molecular
signals required for tissue regression remain unknown. To investigate
physiological tissue regression, we use the mouse hair follicle, which cycles
stereotypically between phases of growth and regression while maintaining a pool
of stem cells to perpetuate tissue regeneration. Here we show by intravital
microscopy in live mice that the regression phase eliminates the majority of the
epithelial cells by two distinct mechanisms: terminal differentiation of
suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore,
we demonstrate that basal epithelial cells collectively act as phagocytes to
clear dying epithelial neighbours. Through cellular and genetic ablation we show
that epithelial cell death is extrinsically induced through transforming growth
factor (TGF)-beta activation and mesenchymal crosstalk. Strikingly, our data show
that regression acts to reduce the stem cell pool, as inhibition of regression
results in excess basal epithelial cells with regenerative abilities. This study
identifies the cellular behaviours and molecular mechanisms of regression that
counterbalance growth to maintain tissue homeostasis.
PMID- 25849773
TI - eIF3 targets cell-proliferation messenger RNAs for translational activation or
repression.
AB - Regulation of protein synthesis is fundamental for all aspects of eukaryotic
biology by controlling development, homeostasis and stress responses. The 13
subunit, 800-kilodalton eukaryotic initiation factor 3 (eIF3) organizes
initiation factor and ribosome interactions required for productive translation.
However, current understanding of eIF3 function does not explain genetic evidence
correlating eIF3 deregulation with tissue-specific cancers and developmental
defects. Here we report the genome-wide discovery of human transcripts that
interact with eIF3 using photoactivatable ribonucleoside-enhanced crosslinking
and immunoprecipitation (PAR-CLIP). eIF3 binds to a highly specific program of
messenger RNAs involved in cell growth control processes, including cell cycling,
differentiation and apoptosis, via the mRNA 5' untranslated region. Surprisingly,
functional analysis of the interaction between eIF3 and two mRNAs encoding the
cell proliferation regulators c-JUN and BTG1 reveals that eIF3 uses different
modes of RNA stem-loop binding to exert either translational activation or
repression. Our findings illuminate a new role for eIF3 in governing a
specialized repertoire of gene expression and suggest that binding of eIF3 to
specific mRNAs could be targeted to control carcinogenesis.
PMID- 25849775
TI - Structural basis for Na(+) transport mechanism by a light-driven Na(+) pump.
AB - Krokinobacter eikastus rhodopsin 2 (KR2) is the first light-driven Na(+) pump
discovered, and is viewed as a potential next-generation optogenetics tool. Since
the positively charged Schiff base proton, located within the ion-conducting
pathway of all light-driven ion pumps, was thought to prohibit the transport of a
non-proton cation, the discovery of KR2 raised the question of how it achieves
Na(+) transport. Here we present crystal structures of KR2 under neutral and
acidic conditions, which represent the resting and M-like intermediate states,
respectively. Structural and spectroscopic analyses revealed the gating
mechanism, whereby the flipping of Asp116 sequesters the Schiff base proton from
the conducting pathway to facilitate Na(+) transport. Together with the structure
based engineering of the first light-driven K(+) pumps, electrophysiological
assays in mammalian neurons and behavioural assays in a nematode, our studies
reveal the molecular basis for light-driven non-proton cation pumps and thus
provide a framework that may advance the development of next-generation
optogenetics.
PMID- 25849777
TI - An ultrafast rechargeable aluminium-ion battery.
AB - The development of new rechargeable battery systems could fuel various energy
applications, from personal electronics to grid storage. Rechargeable aluminium
based batteries offer the possibilities of low cost and low flammability,
together with three-electron-redox properties leading to high capacity. However,
research efforts over the past 30 years have encountered numerous problems, such
as cathode material disintegration, low cell discharge voltage (about 0.55 volts;
ref. 5), capacitive behaviour without discharge voltage plateaus (1.1-0.2 volts
or 1.8-0.8 volts) and insufficient cycle life (less than 100 cycles) with rapid
capacity decay (by 26-85 per cent over 100 cycles). Here we present a
rechargeable aluminium battery with high-rate capability that uses an aluminium
metal anode and a three-dimensional graphitic-foam cathode. The battery operates
through the electrochemical deposition and dissolution of aluminium at the anode,
and intercalation/de-intercalation of chloroaluminate anions in the graphite,
using a non-flammable ionic liquid electrolyte. The cell exhibits well-defined
discharge voltage plateaus near 2 volts, a specific capacity of about 70 mA h g(
1) and a Coulombic efficiency of approximately 98 per cent. The cathode was found
to enable fast anion diffusion and intercalation, affording charging times of
around one minute with a current density of ~4,000 mA g(-1) (equivalent to ~3,000
W kg(-1)), and to withstand more than 7,500 cycles without capacity decay.
PMID- 25849776
TI - Diverse coupling of neurons to populations in sensory cortex.
AB - A large population of neurons can, in principle, produce an astronomical number
of distinct firing patterns. In cortex, however, these patterns lie in a space of
lower dimension, as if individual neurons were "obedient members of a huge
orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus)
and monkey (Macaca mulatta) to investigate the relationship between individual
neurons and the population, and to establish the underlying circuit mechanisms.
We show that neighbouring neurons can differ in their coupling to the overall
firing of the population, ranging from strongly coupled 'choristers' to weakly
coupled 'soloists'. Population coupling is largely independent of sensory
preferences, and it is a fixed cellular attribute, invariant to stimulus
conditions. Neurons with high population coupling are more strongly affected by
non-sensory behavioural variables such as motor intention. Population coupling
reflects a causal relationship, predicting the response of a neuron to
optogenetically driven increases in local activity. Moreover, population coupling
indicates synaptic connectivity; the population coupling of a neuron, measured in
vivo, predicted subsequent in vitro estimates of the number of synapses received
from its neighbours. Finally, population coupling provides a compact summary of
population activity; knowledge of the population couplings of n neurons predicts
a substantial portion of their n(2) pairwise correlations. Population coupling
therefore represents a novel, simple measure that characterizes the relationship
of each neuron to a larger population, explaining seemingly complex network
firing patterns in terms of basic circuit variables.
PMID- 25849779
TI - Correction: association between physical activity knowledge and levels of
physical activity in Chinese adults with type 2 diabetes.
PMID- 25849780
TI - Iron oxide nanorods as high-performance magnetic resonance imaging contrast
agents.
AB - An efficient magnetic resonance imaging (MRI) contrast agent with a high R2
relaxivity value is achieved by controlling the shape of iron oxide to rod like
morphology with a length of 30-70 nm and diameter of 4-12 nm. Fe3O4 nanorods of
70 nm length, encapsulated with polyethyleneimine show a very high R2 relaxivity
value of 608 mM(-1) s(-1). The enhanced MRI contrast of nanorods is attributed to
their higher surface area and anisotropic morphology. The higher surface area
induces a stronger magnetic field perturbation over a larger volume more
effectively for the outer sphere protons. The shape anisotropy contribution is
understood by calculating the local magnetic field of nanorods and spherical
nanoparticles under an applied magnetic field (3 Tesla). As compared to spherical
geometry, the induced magnetic field of a rod is stronger and hence the stronger
magnetic field over a large volume leads to a higher R2 relaxivity of nanorods.
PMID- 25849778
TI - Predictive value of S100-B and copeptin for outcomes following seizure: the
BISTRO International Cohort Study.
AB - OBJECTIVE: To evaluate the performance of S100-B protein and copeptin, in
addition to clinical variables, in predicting outcomes of patients attending the
emergency department (ED) following a seizure. METHODS: We prospectively included
adult patients presented with an acute seizure, in four EDs in France and the
United Kingdom. Participants were followed up for 28 days. The primary endpoint
was a composite of seizure recurrence, all-cause mortality, hospitalization or
rehospitalisation, or return visit in the ED within seven days. RESULTS: Among
the 389 participants included in the analysis, 156 (40%) experienced the primary
endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B
(0.11 MUg/l [95% CI 0.07-0.20] vs 0.09 MUg/l [0.07-0.14]) and copeptin (23 pmol/l
[9-104] vs 17 pmol/l [8-43]) were higher in participants meeting the primary
endpoint. However, both biomarkers were poorly predictive of the primary outcome
with a respective area under the receiving operator characteristic curve of 0.57
[0.51-0.64] and 0.59 [0.54-0.64]. Multivariable logistic regression analysis
identified higher age (odds ratio [OR] 1.3 per decade [1.1-1.5]), provoked
seizure (OR 4.93 [2.5-9.8]), complex partial seizure (OR 4.09 [1.8-9.1]) and
first seizure (OR 1.83 [1.1-3.0]) as independent predictors of the primary
outcome. A second regression analysis including the biomarkers showed no
additional predictive benefit (S100-B OR 3.89 [0.80-18.9] copeptin OR 1 [1.00
1.00]). CONCLUSION: The plasma biomarkers S100-B and copeptin did not improve
prediction of poor outcome following seizure. Higher age, a first seizure, a
provoked seizure and a partial complex seizure are independently associated with
adverse outcomes.
PMID- 25849781
TI - Structural, biochemical, and physiological characterization of photosynthesis in
leaf-derived cup-shaped galls on Litsea acuminata.
AB - BACKGROUND: The source and sink relationships between insect-induced galls and
host plant leaves are interesting. In this research, we collected cup-like galls
induced by Bruggmanniella sp. (Diptera: Cecidomyiidae) on host leaves of Litsea
acuminata and assessed them to investigate source-sink relationships between
galls and host leaves. We characterized several of their photosynthetic
characteristics including chlorophyll fluorescence (Fv/Fm), stomatal conductance,
and photosynthetic capacity, biochemical components such as total soluble sugar,
starches, free amino acids, and soluble proteins. The structural analyses were
performed under confocal, light, and scanning electron microscopies. RESULTS:
Compared with host leaves, galls exhibited slightly lower chlorophyll
fluorescence; however, stomatal conductance and photosynthetic capacity were not
detected at all. Galls accumulated higher total soluble sugars and free amino
acids but less soluble proteins than host leaves. No stomata was observed on
exterior or interior gall surfaces under light or scanning electron microscopy,
but their inner surfaces were covered with fungal hyphae. Confocal imagery showed
a gradient of chloroplasts distribution between gall outer and inner surfaces.
CONCLUSIONS: Our results strongly suggest that leaf-derived cecidomyiid galls are
a type of chlorophyll-deficient non-leaf green tissue and consists on a novel
sink in L. acuminate.
PMID- 25849782
TI - Transcriptomic analysis of differentially expressed genes in an orange-pericarp
mutant and wild type in pummelo (Citrus grandis).
AB - BACKGROUND: The external colour of fruit is a crucial quality feature, and the
external coloration of most citrus fruits is due to the accumulation of
carotenoids. The molecular regulation of carotenoid biosynthesis and accumulation
in pericarp is limited due to the lack of mutant. In this work, an orange
pericarp mutant (MT) which showed altered pigmentation in the pericarp was used
to identify genes potentially related to the regulation of carotenoid
accumulation in the pericarp. RESULTS: High Performance Liquid Chromatography
(HPLC) analysis revealed that the pericarp from MT fruits had a 10.5-fold
increase of beta-carotene content over that of the Wild Type (WT). Quantitative
real-time PCR (qRT-PCR) analysis showed that the expression of all downstream
carotenogenic genes was lower in MT than in WT, suggesting that down-regulation
is critical for the beta-carotene increase in the MT pericarp. RNA-seq analysis
of the transcriptome revealed extensive changes in the MT gene expression level,
with 168 genes down-regulated and 135 genes up-regulated. Gene ontology (GO) and
KEGG pathway analyses indicated seven reliable metabolic pathways are altered in
the mutant, including carbon metabolism, starch and sucrose metabolism and
biosynthesis of amino acids. The transcription factors and genes corresponding to
effected metabolic pathways may involved in the carotenoid regulation was
confirmed by the qRT-PCR analysis in the MT pericarp. CONCLUSIONS: This study has
provided a global picture of the gene expression changes in a novel mutant with
distinct color in the fruit pericarp of pummelo. Interpretation of differentially
expressed genes (DEGs) revealed new insight into the molecular regulation of beta
carotene accumulation in the MT pericarp.
PMID- 25849783
TI - Cardiac structure and function are altered in type 2 diabetes and non-alcoholic
fatty liver disease and associate with glycemic control.
AB - BACKGROUND: Both non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes
increase the risk of developing cardiovascular disease. The metabolic processes
underlying NAFLD and Type 2 diabetes are part of an integrated mechanism but
little is known about how these conditions may differentially affect the heart.
We compared the impact of NAFLD and Type 2 diabetes on cardiac structure,
function and metabolism. METHODS: 19 adults with Type 2 diabetes (62 +/- 8
years), 19 adults with NAFLD (54 +/- 15 years) and 19 healthy controls (56 +/- 14
years) underwent assessment of cardiac structure, function and metabolism using
high resolution magnetic resonance imaging, tagging and spectroscopy at 3.0 T.
RESULTS: Adults with NAFLD and Type 2 diabetes demonstrate concentric remodelling
with an elevated eccentricity ratio compared to controls (1.05 +/- 0.3 vs. 1.12
+/- 0.2 vs. 0.89 +/- 0.2 g/ml; p < 0.05). Despite this, only the Type 2 diabetes
group demonstrate significant systolic and diastolic dysfunction evidenced by a
reduced stroke index (31 +/- 7vs. controls, 38 +/- 10, p < 0.05 ml/m2) and
reduced E/A (0.9 +/- 0.4 vs. controls, 1.9 +/- 1.4, p < 0.05) respectively. The
torsion to shortening ratio was higher in Type 2 diabetes compared to NAFLD (0.58
+/- 0.16 vs. 0.44 +/- 0.13; p < 0.05). Significant associations were observed
between fasting blood glucose/HbA1c and diastolic parameters as well as the
torsion to shortening ratio (all p < 0.05). Phosphocreatine/adenosine
triphosphate ratio was not altered in NAFLD or Type 2 diabetes compared to
controls. CONCLUSIONS: Changes in cardiac structure are evident in adults with
Type 2 diabetes and NAFLD without overt cardiac disease and without changes in
cardiac energy metabolism. Only the Type 2 diabetes group display diastolic and
subendocardial dysfunction and glycemic control may be a key mediator of these
cardiac changes. Therapies should be explored to target these preclinical cardiac
changes to modify cardiovascular risk associated with Type 2 diabetes and NAFLD.
PMID- 25849784
TI - Multi drug and other forms of drug resistant tuberculosis are uncommon among
treatment naive tuberculosis patients in Tanzania.
AB - BACKGROUND: Surveillance and effective management of drug resistance is important
to sustaining tuberculosis (TB) control efforts. We aimed to determine resistance
rates to first line anti tuberculosis drugs and to describe factors associated
with the resistance to any of the first line anti tuberculosis drugs in Dar es
Salaam Tanzania. MATERIALS: Newly diagnosed, TB patients with neither history of
tuberculosis treatment nor isoniazid prophylaxis were included into the study.
Sputum specimens were cultured on either mycobacteria growth indicator tube 960
(MGIT 960) or Lowenstein Jenstein (LJ) medium supplemented with either glycerol
(GLJ) or pyruvate (PLJ). Drug susceptibility for isoniazid, rifampicin,
streptomycin and ethambutol was determined by either Lowenstein-Jensen (LJ)
medium or mycobacteria growth indicator tube 960 (MGIT 960). RESULTS: A total of
933 newly diagnosed TB patients, were included into the study. Multi drug
resistance (MDR) tuberculosis was detected among 2 (0.2%) patients. Resistance to
any of the four tested drugs was detected among 54 (5.8%) patients. Mono
resistance to isoniazid, rifampicin, streptomycin and ethambutol were 21(2.3%), 3
(0.3%), 13 (1.4%), 9 (1.0%) respectively. CONCLUSION: Primary resistance to first
line anti tuberculosis drugs is still low in this setting. Continued vigilance
including periodic national surveillance of anti-tuberculosis resistance is
recommended.
PMID- 25849785
TI - Gate-tunable memristive phenomena mediated by grain boundaries in single-layer
MoS2.
AB - Continued progress in high-speed computing depends on breakthroughs in both
materials synthesis and device architectures. The performance of logic and memory
can be enhanced significantly by introducing a memristor, a two-terminal device
with internal resistance that depends on the history of the external bias
voltage. State-of-the-art memristors, based on metal-insulator-metal (MIM)
structures with insulating oxides, such as TiO2, are limited by a lack of control
over the filament formation and external control of the switching voltage. Here,
we report a class of memristors based on grain boundaries (GBs) in single-layer
MoS2 devices. Specifically, the resistance of GBs emerging from contacts can be
easily and repeatedly modulated, with switching ratios up to ~10(3) and a dynamic
negative differential resistance (NDR). Furthermore, the atomically thin nature
of MoS2 enables tuning of the set voltage by a third gate terminal in a field
effect geometry, which provides new functionality that is not observed in other
known memristive devices.
PMID- 25849786
TI - Nanoscale imaging: Tomography for plasmonics.
PMID- 25849787
TI - A metal-free bifunctional electrocatalyst for oxygen reduction and oxygen
evolution reactions.
AB - The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are
traditionally carried out with noble metals (such as Pt) and metal oxides (such
as RuO2 and MnO2) as catalysts, respectively. However, these metal-based
catalysts often suffer from multiple disadvantages, including high cost, low
selectivity, poor stability and detrimental environmental effects. Here, we
describe a mesoporous carbon foam co-doped with nitrogen and phosphorus that has
a large surface area of ~1,663 m(2) g(-1) and good electrocatalytic properties
for both ORR and OER. This material was fabricated using a scalable, one-step
process involving the pyrolysis of a polyaniline aerogel synthesized in the
presence of phytic acid. We then tested the suitability of this N,P-doped carbon
foam as an air electrode for primary and rechargeable Zn-air batteries. Primary
batteries demonstrated an open-circuit potential of 1.48 V, a specific capacity
of 735 mAh gZn(-1) (corresponding to an energy density of 835 Wh kgZn(-1)), a
peak power density of 55 mW cm(-2), and stable operation for 240 h after
mechanical recharging. Two-electrode rechargeable batteries could be cycled
stably for 180 cycles at 2 mA cm(-2). We also examine the activity of our carbon
foam for both OER and ORR independently, in a three-electrode configuration, and
discuss ways in which the Zn-air battery can be further improved. Finally, our
density functional theory calculations reveal that the N,P co-doping and graphene
edge effects are essential for the bifunctional electrocatalytic activity of our
material.
PMID- 25849788
TI - Nanoscale optical tomography with cathodoluminescence spectroscopy.
AB - Tomography has enabled the characterization of the Earth's interior,
visualization of the inner workings of the human brain, and three-dimensional
reconstruction of matter at the atomic scale. However, tomographic techniques
that rely on optical excitation or detection are generally limited in their
resolution by diffraction. Here, we introduce a tomographic technique-
cathodoluminescence spectroscopic tomography--to probe optical properties in
three dimensions with nanometre-scale spatial and spectral resolution. We first
obtain two-dimensional cathodoluminescence maps of a three-dimensional
nanostructure at various orientations. We then use the method of filtered back
projection to reconstruct the cathodoluminescence intensity at each wavelength.
The resulting tomograms allow us to locate regions of efficient
cathodoluminescence in three dimensions across visible and near-infrared
wavelengths, with contributions from material luminescence and radiative decay of
electromagnetic eigenmodes. The experimental signal can be further correlated
with the radiative local density of optical states in particular regions of the
reconstruction. We demonstrate how cathodoluminescence tomography can be used to
achieve nanoscale three-dimensional visualization of light-matter interactions by
reconstructing a three-dimensional metal-dielectric nanoresonator.
PMID- 25849789
TI - Reversible oxygen scavenging at room temperature using electrochemically reduced
titanium oxide nanotubes.
AB - A material capable of rapid, reversible molecular oxygen uptake at room
temperature is desirable for gas separation and sensing, for technologies that
require oxygen storage and oxygen splitting such as fuel cells (solid-oxide fuel
cells in particular) and for catalytic applications that require reduced oxygen
species (such as removal of organic pollutants in water and oil-spill
remediation). To date, however, the lowest reported temperature for a reversible
oxygen uptake material is in the range of 200-300 degrees C, achieved in the
transition metal oxides SrCoOx (ref. 1) and LuFe2O(4+x) (ref. 2) via thermal
cycling. Here, we report rapid and reversible oxygen scavenging by Ti(2-x)
nanotubes at room temperature. The uptake and release of oxygen is accomplished
by an electrochemical rather than a standard thermal approach. We measure an
oxygen uptake rate as high as 14 mmol O2 g(-1) min(-1), ~2,400 times greater than
commercial, irreversible oxygen scavengers. Such a fast oxygen uptake at a
remarkably low temperature suggests a non-typical mechanistic pathway for the re
oxidation of Ti(2-x). Modelling the diffusion of oxygen, we show that a likely
pathway involves 'exceptionally mobile' interstitial oxygen produced by the
oxygen adsorption and decomposition dynamics, recently observed on the surface of
anatase.
PMID- 25849790
TI - Discolored ureteral stents: findings in urinalysis and urine culture.
AB - OBJECTIVE: Discolored ureteral stents are sometimes encountered in daily clinical
practice; however, the mechanism(s) underlying the development of discolored
ureteral stents remain unknown. In this study, we retrospectively analyzed the
characteristics of discolored ureteral stents based on the results of a
urinalysis and urine culture. MATERIALS & METHODS: We identified a total of 26
patients with discolored ureteral stents and compared the findings in the
urinalyses and urine culture in 21 discolored versus 45 non-colored ureteral
stents. RESULTS: The median and mean (+/- SD) duration of stenting time was 78.0
and 81.3 (+/- 21.3) days for the discolored ureteral stents and 69.0 and 74.9 (+/
19.8) days for the non-colored ureteral stents, respectively (P = 0.25). The
discolored ureteral stents were associated with a higher mean urine pH than the
non-colored ureteral stents (mean: 6.4 vs 6.0, P< 0.05). There were no
significant differences between the two groups in the RBC (P = 0.51) and WBC (P =
0.35) counts in the urinalyses. In addition, the rate of a positive culture in
the patients with discolored stents [20 of 21 (95.2%)] was significantly (P
<0.01) higher than that observed in the patients with non-colored ureteral stents
[33 of 45 (73.3%)]. CONCLUSIONS: In this study, the subjects with discolored
ureteral stents showed a significantly higher likelihood of having a positive
urine culture and also demonstrated higher pH values in the urinalyses. However,
no clear cut-off point to predict discoloration was indicated.
PMID- 25849791
TI - Inhibition of PKCbeta2 overexpression ameliorates myocardial
ischaemia/reperfusion injury in diabetic rats via restoring caveolin-3/Akt
signaling.
AB - Activation of PKCbeta (protein kinase Cbeta) plays a critical role in myocardial
I/R (ischaemia/reperfusion) injury in non-diabetic rodents. In the myocardium of
diabetes, PKCbeta2 overexpression is associated with increased vulnerability to
post-ischaemic I/R injury with concomitantly impaired cardiomyocyte Cav
(caveolin)-3 and Akt signalling compared with non-diabetic rats. We hypothesized
that myocardial PKCbeta overexpression in diabetes exacerbates myocardial I/R
injury through impairing Cav-3/Akt signalling. Streptozotocin-induced diabetic
rats were treated with the selective PKCbeta inhibitor ruboxistaurin (RBX, 1
mg/kg per day) for 4 weeks, starting from 1 week after diabetes induction, before
inducing myocardial I/R achieved by occluding the left descending coronary artery
followed by reperfusion. Cardiac function was measured using a pressure-volume
conductance system. In an in vitro study, cardiac H9C2 cells were exposed to high
glucose (30 mmol/l) and subjected to hypoxia followed by reoxygenation (H/R) in
the presence or absence of the selective PKCbeta2 inhibitor CGP53353 (1 MUmol/l),
siRNAs of PKCbeta2 or Cav-3 or Akt. Cell apoptosis and mitochondrial membrane
potential were assessed by TUNEL (terminal deoxynucleotidyltransferase-mediated
dUTP nick-end labelling) and JC-1 staining respectively. RBX significantly
decreased post-ischaemic myocardial infarct size (35+/-5% compared with 49+/-3%
in control, P<0.05) and attenuated cardiac dysfunction, and prevented the
reduction in cardiac Cav-3 and enhanced phosphorylated/activated Akt (p-Akt) in
diabetic rats (P<0.05). H/R increased cardiomyocyte injury under high glucose
conditions as was evident by increased TUNEL-positive and increased JC-1
monomeric cells (P<0.05 compared with control), accompanied with increased
PKCbeta2 phosphorylation/activation and decreased Cav-3 expression. Either
CGP53353 or PKCbeta2 siRNA significantly attenuated all of these changes and
enhanced p-Akt. Cav-3 gene knockdown significantly reduced p-Akt and increased
post-hypoxic cellular and mitochondrial injury despite a concomitant reduction in
PKCbeta2 phosphorylation. PKCbeta2 inhibition with RBX protects diabetic hearts
from myocardial I/R injury through Cav-3-dependent activation of Akt.
PMID- 25849792
TI - Rhodium-catalysed synthesis of multi-substituted silylindenes from aryl alkynes
and hydrosilanes via C-H bond activation.
AB - We successfully developed rhodium-catalysed synthesis of multi-substituted
silylindenes from 2 equivalents of aryl alkynes and 1 equivalent of hydrosilanes
in moderate to good yields via C-H bond activation for the first time. The silyl
groups of the obtained silylindenes could be converted to several other
functional groups.
PMID- 25849793
TI - Probing ADAMTS13 substrate specificity using phage display.
AB - Von Willebrand factor (VWF) is a large, multimeric protein that regulates
hemostasis by tethering platelets to the subendothelial matrix at sites of
vascular damage. The procoagulant activity of plasma VWF correlates with the
length of VWF multimers, which is proteolytically controlled by the
metalloprotease ADAMTS13. To probe ADAMTS13 substrate specificity, we created
phage display libraries containing randomly mutated residues of a minimal
ADAMTS13 substrate fragment of VWF, termed VWF73. The libraries were screened for
phage particles displaying VWF73 mutant peptides that were resistant to
proteolysis by ADAMTS13. These peptides exhibited the greatest mutation frequency
near the ADAMTS13 scissile residues. Kinetic assays using mutant and wild-type
substrates demonstrated excellent agreement between rates of cleavage for mutant
phage particles and the corresponding mutant peptides. Cleavage resistance of
selected mutations was tested in vivo using hydrodynamic injection of
corresponding full-length expression plasmids into VWF-deficient mice. These
studies confirmed the resistance to cleavage resulting from select amino acid
substitutions and uncovered evidence of alternate cleavage sites and recognition
by other proteases in the circulation of ADAMTS13 deficient mice. Taken together,
these studies demonstrate the key role of specific amino acids residues including
P3-P2' and P11', for substrate specificity and emphasize the importance in
flowing blood of other ADAMTS13-VWF exosite interactions outside of VWF73.
PMID- 25849794
TI - The ABC exporter MsbA probed by solid state NMR - challenges and opportunities.
AB - ATP binding cassette (ABC) transporters form a superfamily of integral membrane
proteins involved in translocation of substrates across the membrane driven by
ATP hydrolysis. Despite available crystal structures and extensive biochemical
data, many open questions regarding their transport mechanisms remain. Therefore,
there is a need to explore spectroscopic techniques such as solid state NMR in
order to bridge the gap between structural and mechanistic data. In this study,
we investigate the feasibility of using Escherichia coli MsbA as a model ABC
transporter for solid state NMR studies. We show that optimised solubilisation
and reconstitution procedures enable preparing stable and homogenous protein
samples. Depending on the duration of solubilisation, MsbA can be obtained in
either an apo- or in a native lipid A bound form. Building onto these
optimisations, the first promising MAS-NMR spectra with narrow lines have been
recorded. However, further sensitivity improvements are required so that complex
NMR experiments can be recorded within a reasonable amount of time. We therefore
demonstrate the usability of paramagnetic doping for rapid data acquisition and
explore dynamic nuclear polarisation as a method for general signal enhancement.
Our results demonstrate that solid state NMR provides an opportunity to address
important biological questions related to complex mechanisms of ABC transporters.
PMID- 25849796
TI - Are regulation-driven performance criteria still acceptable? - The German point
of view.
AB - Performance criteria should be a challenge for the laboratories to improve their
quality. In countries with mandatory proficiency testing, the definition of
performance criteria is a particular issue. If the definition of performance
criteria is mandated from the regulatory bodies to medico-scientific
institutions, scientific approaches (i.e., based on biological variation), the
state-of-the-art approach (i.e., based on technical feasibility) as well as
medical needs can be used to set up performance criteria such as the Richtlinie
der Bundesarztekammer (RiliBAK; Guideline of the German Medical Association on
Quality Assurance in Medical Laboratory Examinations) in Germany. The experiences
with RiliBAK show that these performance criteria have to be revised on an
ongoing basis.
PMID- 25849795
TI - Homeostatic control of biological membranes by dedicated lipid and membrane
packing sensors.
AB - Biological membranes are dynamic and complex assemblies of lipids and proteins.
Eukaryotic lipidomes encompass hundreds of distinct lipid species and we have
only begun to understand their role and function. This review focuses on recent
advances in the field of lipid sensors and discusses methodical approaches to
identify and characterize putative sensor domains. We elaborate on the role of
integral and conditionally membrane-associated sensor proteins, their molecular
mechanisms, and identify open questions in the emerging field of membrane
homeostasis.
PMID- 25849797
TI - National survey on appropriateness of clinical biochemistry reporting in China.
AB - BACKGROUND: Accurate and reliable testing reports play an important role in the
prevention, diagnosis, treatment and prognosis of disease. However, little is
known about the appropriateness of laboratory testing reporting in China. This
national survey takes clinical biochemistry as an example to investigate the
state of reporting appropriateness in our country. METHODS: An electronic
questionnaire was sent to 1209 laboratories. The participants were asked to
retrospectively evaluate the error rates of the following quality indicators:
report template integrity, report content filling integrity, report delay, report
recall, non-conformities between instrument and laboratory information system
(LIS) data, non-conformities between report and request, report notification
error, and report modification. Mann-Whitney and Kruskal-Wallis tests were used
to identify the potential impacts of reporting appropriateness. RESULTS: A total
of 662 of the 1209 laboratories (55%) submitted the survey results, with three
returning incomplete data. For the integrity of the report, only 31% of the
laboratories had a complete report template that contained all of 21 elements. In
addition, the overall error rate of content filling integrity was 45.9% for
19,770 pieces of reports. The overall sigma-values of other six quality
indicators were all >4, and no significant difference was found among different
departments. Group comparison suggested that reporting electronically had a
better performance. CONCLUSIONS: The laboratory reporting system in China needs
to improve, particularly the integrity of the report. Strengthening information
technology will not only promote reporting appropriateness, but also guarantee
accurate, standardized and traceable data collection and long-term monitoring.
PMID- 25849798
TI - Comparison of splitting methods on survival tree.
AB - We compare splitting methods for constructing survival trees that are used as a
model of survival time based on covariates. A number of splitting criteria on the
classification and regression tree (CART) have been proposed by various authors,
and we compare nine criteria through simulations. Comparative studies have been
restricted to criteria that suppose the survival model for each terminal node in
the final tree as a non-parametric model. As the main results, the criteria using
the exponential log-likelihood loss, log-rank test statistics, the deviance
residual under the proportional hazard model, or square error of martingale
residual are recommended when it appears that the data have constant hazard with
the passage of time. On the other hand, when the data are thought to have
decreasing hazard with passage of time, the criterion using the two-sample test
statistic, or square error of deviance residual would be optimal. Moreover, when
the data are thought to have increasing hazard with the passage of time, the
criterion using the exponential log-likelihood loss, or impurity that combines
observed times and the proportion of censored observations would be the best. We
also present the results of an actual medical research to show the utility of
survival trees.
PMID- 25849799
TI - Within-Subject Mediation Analysis in AB/BA Crossover Designs.
AB - Crossover trials are widely used to assess the effect of a reversible exposure on
an outcome of interest. To gain further insight into the underlying mechanisms of
this effect, researchers may be interested in exploring whether or not it runs
through a specific intermediate variable: the mediator. Mediation analysis in
crossover designs has received scant attention so far and is mostly confined to
the traditional Baron and Kenny approach. We aim to tackle mediation analysis
within the counterfactual framework and elucidate the assumptions under which the
direct and indirect effects can be identified in AB/BA crossover studies.
Notably, we show that both effects are identifiable in certain statistical
models, even in the presence of unmeasured time-independent (or upper-level)
confounding of the mediator-outcome relation. Employing the mediation formula, we
derive expressions for the direct and indirect effects in within-subject designs
for continuous outcomes that lend themselves to linear modelling, under a large
variety of settings. We discuss an estimation approach based on regressing
differences in outcomes on differences in mediators and show how to allow for
period effects as well as different types of moderation. The performance of this
approach is compared to other existing methods through simulations and is
illustrated with data from a neurobehavioural study. Lastly, we demonstrate how a
sensitivity analysis can be performed that is able to assess the robustness of
both the direct and indirect effect against violation of the "no unmeasured lower
level mediator-outcome confounding" assumption.
PMID- 25849800
TI - A universal approximate cross-validation criterion for regular risk functions.
AB - Selection of estimators is an essential task in modeling. A general framework is
that the estimators of a distribution are obtained by minimizing a function (the
estimating function) and assessed using another function (the assessment
function). A classical case is that both functions estimate an information risk
(specifically cross-entropy); this corresponds to using maximum likelihood
estimators and assessing them by Akaike information criterion (AIC). In more
general cases, the assessment risk can be estimated by leave-one-out cross
validation. Since leave-one-out cross-validation is computationally very
demanding, we propose in this paper a universal approximate cross-validation
criterion under regularity conditions (UACVR). This criterion can be adapted to
different types of estimators, including penalized likelihood and maximum a
posteriori estimators, and also to different assessment risk functions, including
information risk functions and continuous rank probability score (CRPS). UACVR
reduces to Takeuchi information criterion (TIC) when cross-entropy is the risk
for both estimation and assessment. We provide the asymptotic distributions of
UACVR and of a difference of UACVR values for two estimators. We validate UACVR
using simulations and provide an illustration on real data both in the
psychometric context where estimators of the distributions of ordered categorical
data derived from threshold models and models based on continuous approximations
are compared.
PMID- 25849801
TI - The effect of Terminalia chebula extract vs. silver sulfadiazine on burn wounds
in rats.
AB - BACKGROUND: The aim of this study was to evaluate the efficacy of ethanol extract
of Terminalia chebula in the treatment of hot water-induced burn wounds and to
compare the results with silver sulfadiazine (SSD) in rats. METHODS: Five groups
of ten rats were burned with hot water. Animals were administrated with topical
cream at control, normal saline, 5%, 10% T. chebula extracts and standard SSD
creams. Several parameters were assessed, including wound area, visual inspection
of wound, bacteriology assessment, percentage of wound contraction and
histopathological examination. RESULTS: The average area of wound on 10th day was
11.2 +/- 3.3, 11 +/- 3.2, 8.5 +/- 2.3, 9.5 +/- 4.2 and 5.1 +/- 2.2 cm(2) for
SSD1%, base cream, normal saline, herbal extract 5% and 10%, respectively. T.
chebula 10% cream exhibited lower wound size than SSD1% and control groups at
10th day post burn injury. On day 15, the percentage of wound contraction in T.
chebula was 5% and 10% more than 18% and 53% in comparison to SSD1% group,
respectively. Histopathological results exhibited well-formed horizontally
oriented collagen fibers for appropriate tension. Strength of scar on burned
tissue was better in T. chebula 5% and 10% as compared with control and SSD
groups. CONCLUSIONS: The results of this study showed that T. chebula extract was
capable of accelerating wound healing in rats by wound contraction, and had
beneficial effects more than SSD 1% cream in the management of burn injury.
PMID- 25849802
TI - Synthesis, characterization, crystal structure and antimicrobial activity of
copper(II) complexes with the Schiff base derived from 2-hydroxy-4
methoxybenzaldehyde.
AB - A novel Schiff base, ethyl 4-[(E)-(2-hydroxy-4-methoxyphenyl)methylene
amino]benzoate (HL), was prepared and structurally characterized on the basis of
elemental analyses, (1)H NMR, (13)C NMR, UV-Vis and IR spectral data. Six new
copper(II) complexes, [Cu(L)(NO3)(H2O)2] (1), [Cu(L)2] (2), [Cu(L)(OAc)] (3),
[Cu2 (L)2Cl2(H2O)4] (4), [Cu(L)(ClO4)(H2O)] (5) and [Cu2(L2S)(ClO4)(H2O)]ClO4.H2O
(6) have been synthesized. The characterization of the newly formed compounds was
done by IR, UV-Vis, EPR, FAB mass spectroscopy, elemental and thermal analysis,
magnetic susceptibility measurements and molar electric conductivity. The crystal
structures of Schiff base and the complex [Cu2(L2S)(ClO4)(H2O)]ClO4.H2O (6) have
been determined by single crystal X-ray diffraction studies. Both copper atoms
display a distorted octahedral coordination type [O4NS]. This coordination is
ensured by three phenol oxygen, two of which being related to the u-oxo-bridge,
the nitrogen atoms of the azomethine group and the sulfur atoms that come from
the polydentate ligand. The in vitro antimicrobial activity against Escherichia
coli ATCC 25922, Salmonella enteritidis, Staphylococcus aureus ATCC 25923,
Enterococcus and Candida albicans strains was studied and compared with that of
free ligand. The complexes 1, 2, 5 showed a better antimicrobial activity than
the Schiff base against the tested microorganisms.
PMID- 25849803
TI - X-ray structures of precursors of styrylpyridine-derivatives used to obtain 4
((E)-2-(pyridin-2-yl)vinyl)benzamido-TEMPO: synthesis and characterization.
AB - The synthesis and characterization of the precursor isomers trans-4-(2-(pyridin-2
yl)vinylbenzaldehyde (I), trans-4-(2-(pyridin-4-yl)vinylbenzaldehyde (II), trans
4-(2-(pyridin-2-yl)vinylbenzoic acid (III) and (E)-4-(2-(pydridin-4
yl)vinylbenzoic acid (IV) are reported. These compounds were prepared in order to
obtain trans-4-((E)-2-(pyridin-2-yl)vinyl)benzamide-TEMPO (V). Compounds I and II
were obtained by using a Knoevenagel reaction in the absence of a condensing
agent and solvent. Oxidation of the aldehyde group using the Jones reagent
afforded the corresponding acid forms III and IV. A condensation reaction with 4
amino-TEMPO using oxalyl chloride/DMF/CH2Cl2 provided the 4-((E)-2-(pyridin-2
yl)vinyl)benzamide-TEMPO. Single crystals of compounds I, II and III were
obtained and characterized by X-ray diffraction. Compound I belongs to space
group P2(1)/c, a = 12.6674(19) A, b = 7.2173(11) A, c = 11.5877(14) A, b =
97.203(13) degrees and the asymmetric unit was Z = 4, whereas compound II was in
the space group P2(1), with a = 3.85728(9) A, b = 10.62375(19) A, c = 12.8625(2)
A, b = 91.722 (2) degrees and the asymmetric unit was Z = 2. Compound III
crystallized as single colorless needle crystals, belonging to the monoclinic
system with space group P2(1), with Z = 2, with a = 3.89359(7) A, b = 17.7014(3)
A, c = 8.04530(12) A, b = 94.4030 (16) degrees . All compounds were completely
characterized by IR, (1)H-NMR, EI-MS and UV-Vis.
PMID- 25849804
TI - Characterization at 25 degrees C of sodium hyaluronate in aqueous solutions
obtained by transport techniques.
AB - Mutual diffusion coefficients, D, were determined for aqueous solutions of sodium
hyaluronate (NaHy) at 25 degrees C and concentrations ranging from 0.00 to 1.00
g.dm(-3) using the Taylor dispersion technique. From these experimental data, it
was possible to estimate some parameters, such as the hydrodynamic radius Rh, and
the diffusion coefficient at infinitesimal concentration, D0, of hyaluronate ion,
permitting us to have a better understanding of the structure of these systems of
sodium hyaluronate in aqueous solutions. The additional viscosity measurements
were done and Huggins constant, kH, and limiting viscosity number, [eta], were
computed for interaction NaHy/water and NaHy/NaHy determination.
PMID- 25849805
TI - Three new pigment protein tyrosine phosphatases inhibitors from the insect
parasite fungus Cordyceps gracilioides: terreusinone A, pinophilin C and
cryptosporioptide A.
AB - Three new pigment compounds--terreusinone A (1), pinophilin C (2) and
cryptosporioptide A (3)-were isolated from a solid culture of Cordyceps
gracilioides. The structures of these compounds were determined by extensive
spectroscopic analysis including HRESIMS, 1D- and 2D-NMR. The structure of
terreusinone A (1) was further confirmed by single-crystal X-ray crystallographic
diffraction analysis. In an in vitro activity assay, 1, 2 and 3 exhibited high
inhibitory activity against PTP1B, SHP2, CDC25B, LAR and SHP1. Terreusinone A (1)
inhibited PTP1B, SHP2, CDC25B, LAR and SHP1 enzyme with IC50 values 12.5, >50,
4.1, 10.6, 5.6 ug/mL, respectively; pinophilin C (2) with IC50 values 6.8, 8.0,
4.5, 4.7, 3.4 ug/mL, respectively; and cryptosporioptide A (3) with IC50 values
7.3, 5.7, 7.6, >50, 4.9 ug/mL, respectively.
PMID- 25849806
TI - Anisotropy in bone demineralization revealed by polarized far-IR spectroscopy.
AB - Bone material is composed of an organic matrix of collagen fibers and apatite
nanoparticles. Previously, vibrational spectroscopy techniques such as infrared
(IR) and Raman spectroscopy have proved to be particularly useful for
characterizing the two constituent organic and inorganic phases of bone. In this
work, we tested the potential use of high intensity synchrotron-based far-IR
radiation (50-500 cm(-1)) to gain new insights into structure and chemical
composition of bovine fibrolamellar bone. The results from our study can be
summarized in the following four points: (I) compared to far-IR spectra obtained
from synthetic hydroxyapatite powder, those from fibrolamellar bone showed
similar peak positions, but very different peak widths; (II) during stepwise
demineralization of the bone samples, there was no significant change neither to
far-IR peak width nor position, demonstrating that mineral dissolution occurred
in a uniform manner; (III) application of external loading on fully demineralized
bone had no significant effect on the obtained spectra, while dehydration of
samples resulted in clear differences. (IV) using linear dichroism, we showed
that the anisotropic structure of fibrolamellar bone is also reflected in
anisotropic far-IR absorbance properties of both the organic and inorganic
phases. Far-IR spectroscopy thus provides a novel way to functionally
characterize bone structure and chemistry, and with further technological
improvements, has the potential to become a useful clinical diagnostic tool to
better assess quality of collagen-based tissues.
PMID- 25849808
TI - Unique photophysical properties of 9-styryl-1,2-dihydropyrrolo[3,4-beta]indolizin
3-one and its efficient synthesis via direct C-H activation.
AB - A styryl Seoul-Fluor (SF) skeleton was rationally designed by introducing an
olefin unit at the C-9 of 1,2-dihydropyrrolo[3,4-beta]indolizin-3-one via
regioselective direct C-H activation. We synthesized a series of styryl SF
analogues, maintaining unique photophysical properties that can be systematically
controlled by the electronic characteristics of the substituents, with an average
bathochromic shift of 39 nm in emission maxima.
PMID- 25849807
TI - Assessment of brainstem function with auricular branch of vagus nerve stimulation
in Parkinson's disease.
AB - BACKGROUND: The efferent dorsal motor nucleus of the vagal nuclei complex may
degenerate early in the course of Parkinson's disease (PD), while efferent
nucleus ambiguous, the principal source of parasympathetic vagal neurons
innervating the heart, and afferent somatosensory nuclei remain intact.
OBJECTIVE: To obtain neurophysiological evidence related to this pattern, we
tested processing of afferent sensory information transmitted via the auricular
branch of the vagus nerve (ABVN) which is known to be connected to autonomic
regulation of cardiac rhythm. METHODS: In this cross-sectional observational
study, we recorded (i) somatosensory evoked potentials (ABVN-SEP) and (ii)
cutaneo-cardioautonomic response elicited by stimulation of the ABVN (modulation
of heart-rate variability (HRV index; low frequency power, ln(LF), high frequency
power, ln(HF); ln(LF/HF) ratio)) in 50 PD patients and 50 age and sex matched
healthy controls. Additionally, auditory evoked potentials and trigeminal nerve
SEP were assessed. RESULTS: Neither ABVN-SEP nor any of the other functional
brainstem parameters differed between patients and controls. Although HRV index
was decreased in PD patients, modulation of ln(LF/HF) by ABVN-stimulation, likely
indicating cardiac parasympathetic activation, did not differ between both
groups. CONCLUSIONS: Findings do not point to prominent dysfunction of processing
afferent information from ABVN and its connected parasympathetic cardiac pathway
in PD. They are consistent with the known pattern of degeneration of the vagal
nuclei complex of the brainstem.
PMID- 25849809
TI - Clinical outcomes of early and later physical therapist services for older adults
with back pain.
AB - BACKGROUND CONTEXT: The timing of physical therapy (PT) services and its
association with later function and pain are not clear, especially in older
adults. PURPOSE: The purpose of this study was to compare clinical outcomes of
patients receiving early or later PT services with those not receiving PT among
older adults presenting to primary care for a new visit for back pain. STUDY
DESIGN/SETTING: Prospective cohort study using the Back Pain Outcomes Using
Longitudinal Data registry. PATIENT SAMPLE: A total of 3,705 adults 65 years and
older with a new visit for back pain were included. OUTCOME MEASURES: The outcome
measures were Roland-Morris Disability Questionnaire (RMDQ), Pain Numerical
Rating Scales, and EuroQol-5D. METHODS: We studied two phases of PT utilization:
early (0-28 days) and later (3-6 months). At baseline, we selected the
participants with complete 12 months of patient-reported outcomes and electronic
medical record data. Early PT was defined as initiating PT less than or equal to
28 days from the index visit for back pain. The no early PT group consisted of
patients with no PT, no injections, no surgery, and no chiropractic within 28
days. We restricted the later phase analysis to patients with pain greater than 2
of 10 and an RMDQ score greater than 4 to create a subsample of patients with
continuing clinically important back pain. We defined later PT as initiating PT
between 3 and 6 months after the index visit. The no later PT group consisted of
patients without any PT during this time. We used propensity score matching
followed by multiple linear regression to estimate the mean difference in
outcome. Sensitivity analysis examined clinically important change and dose of PT
use among the early PT group. RESULTS: The early PT group had better functional
status with an adjusted mean RMDQ of 1.1 points less than the no early PT group
(95% confidence interval: -2.2, -0.1) and less back pain of -0.5 (-0.9, -0.1) at
12 months. There was no difference between early PT groups at 3 and 6 months. The
odds of a 30% improvement in function or pain were not different between these
matched groups at 12 months, but the early PT group had increased odds of a 50%
improvement in function at 12 months (odds ratio: 1.58, 95% confidence interval:
1.04, 2.40). There was no difference between later groups at 12 months. Greater
dose of PT use within the early PT group was associated with better functional
status (p= .01). CONCLUSIONS: We found that among older adults presenting to
their primary care providers for a new episode of back pain, early referral to PT
resulted in no or minimal differences in pain, function, or health-related
quality at 3, 6, or 12 months compared with a matched group that did not receive
early PT. Secondary analysis show that patients initiating early PT may be
somewhat more likely to experience 50% improvement in function at 12 months.
PMID- 25849810
TI - Lady Liberty and Godfather Death as candidates for linguistic relativity?
Scrutinizing the gender congruency effect on personified allegories with explicit
and implicit measures.
AB - Linguistic relativity--the idea that language affects thought by way of its
grammatical categorizations--has been controversially debated for decades. One of
the contested cases is the grammatical gender of nouns, which is claimed to
affect how their referents are conceptualized (i.e., as rather female or male in
congruence with the grammatical gender of the noun), especially when used
allegorically. But is this association strong enough to be detected in implicit
measures, and, if so, can we disentangle effects of grammatical gender and
allegorical association? Three experiments with native speakers of German tackled
these questions. They revealed a gender congruency effect on allegorically used
nouns, but this effect was stronger with an explicit measure (assignment of
biological sex) than with an implicit measure (Extrinsic Affective Simon Task)
and disappeared in the implicit measure when grammatical gender and allegorical
associations were set into contrast. Taken together, these findings indicate that
the observed congruency effect was driven by the association of nouns with
personifications rather than by their grammatical gender. In conclusion, we also
discuss implications of these findings for linguistic relativity.
PMID- 25849811
TI - Erratum: Allergic diseases and asthma in the family predict the persistence and
onset-age of asthma: a prospective cohort study.
PMID- 25849812
TI - Combining the sterile insect technique with the incompatible insect technique: I
impact of wolbachia infection on the fitness of triple- and double-infected
strains of Aedes albopictus.
AB - The mosquito species Aedes albopictus is a major vector of the human diseases
dengue and chikungunya. Due to the lack of efficient and sustainable methods to
control this mosquito species, there is an increasing interest in developing and
applying the sterile insect technique (SIT) and the incompatible insect technique
(IIT), separately or in combination, as population suppression approaches. Ae.
albopictus is naturally double-infected with two Wolbachia strains, wAlbA and
wAlbB. A new triple Wolbachia-infected strain (i.e., a strain infected with
wAlbA, wAlbB, and wPip), known as HC and expressing strong cytoplasmic
incompatibility (CI) in appropriate matings, was recently developed. In the
present study, we compared several fitness traits of three Ae. albopictus strains
(triple-infected, double-infected and uninfected), all of which were of the same
genetic background ("Guangzhou City, China") and were reared under the same
conditions. Investigation of egg-hatching rate, survival of pupae and adults, sex
ratio, duration of larval stages (development time from L1 to pupation), time to
emergence (development time from L1 to adult emergence), wing length, female
fecundity and adult longevity indicated that the presence of Wolbachia had only a
minimal effect on host fitness. Based on this evidence, the HC strain is
currently under consideration for mass rearing and application in a combined SIT
IIT strategy to control natural populations of Ae. albopictus in mainland China.
PMID- 25849813
TI - Single bacteria movement tracking by online microscopy--a proof of concept study.
AB - In this technical report we demonstrate a low-cost online unit allowing movement
tracking of flagellated bacteria on a single-cell level during fermentation
processes. The system's ability to distinguish different metabolic states
(viability) of bacteria by movement velocity was investigated. A flow-through
cuvette with automatically adjustable layer thickness was developed. The cuvette
can be used with most commercially available laboratory microscopes equipped with
40* amplification and a digital camera. In addition, an automated sample
preparation unit and a software module was developed measuring size, moved
distance, and speed of bacteria. In a proof of principle study the movement
velocities of Bacillus amyloliquefaciens FZB42 during three batch fermentation
processes were investigated. In this process the bacteria went through different
metabolic states, vegetative growth, diauxic shift, vegetative growth after
diauxic shift, and sporulation. It was shown that the movement velocities during
the different metabolic states significantly differ from each other. Therefore,
the described setup has the potential to be used as a bacteria viability
monitoring tool. In contrast to some other techniques, such as electro-optical
techniques, this method can even be used in turbid production media.
PMID- 25849814
TI - Functional gene composition, diversity and redundancy in microbial stream biofilm
communities.
AB - We surveyed the functional gene composition and diversity of microbial biofilm
communities in 18 New Zealand streams affected by different types of catchment
land use, using a comprehensive functional gene array, GeoChip 3.0. A total of
5,371 nutrient cycling and energy metabolism genes within 65 gene families were
detected among all samples (342 to 2,666 genes per stream). Carbon cycling genes
were most common, followed by nitrogen cycling genes, with smaller proportions of
sulphur, phosphorus cycling and energy metabolism genes. Samples from urban and
native forest streams had the most similar functional gene composition, while
samples from exotic forest and rural streams exhibited the most variation. There
were significant differences between nitrogen and sulphur cycling genes detected
in native forest and urban samples compared to exotic forest and rural samples,
attributed to contrasting proportions of nitrogen fixation, denitrification, and
sulphur reduction genes. Most genes were detected only in one or a few samples,
with only a small minority occurring in all samples. Nonetheless, 42 of 65 gene
families occurred in every sample and overall proportions of gene families were
similar among samples from contrasting streams. This suggests the existence of
functional gene redundancy among different stream biofilm communities despite
contrasting taxonomic composition.
PMID- 25849815
TI - Associations between ultrasound measures of abdominal fat distribution and
indices of glucose metabolism in a population at high risk of type 2 diabetes:
the ADDITION-PRO study.
AB - AIMS: Visceral adipose tissue measured by CT or MRI is strongly associated with
an adverse metabolic risk profile. We assessed whether similar associations can
be found with ultrasonography, by quantifying the strength of the relationship
between different measures of obesity and indices of glucose metabolism in a
population at high risk of type 2 diabetes. METHODS: A cross-sectional analysis
of 1342 participants of the ADDITION-PRO study. We measured visceral adipose
tissue and subcutaneous adipose tissue with ultrasonography, anthropometrics and
body fat percentage by bioelectrical impedance. Indices of glucose metabolism
were derived from a three point oral glucose tolerance test. Linear regression of
obesity measures on indices of glucose metabolism was performed. RESULTS: Mean
age was 66.2 years, BMI 26.9kg/m2, subcutaneous adipose tissue 2.5cm and visceral
adipose tissue 8.0cm. All measures of obesity were positively associated with
indicators of glycaemia and inversely associated with indicators of insulin
sensitivity. Associations were of equivalent magnitude except for subcutaneous
adipose tissue and the visceral/subcutaneous adipose tissue ratio, which showed
weaker associations. One standard deviation difference in BMI, visceral adipose
tissue, waist circumference, waist/height ratio and body fat percentage
corresponded approximately to 0.2mmol/l higher fasting glucose, 0.7mmol/l higher
2-hr glucose, 0.06-0.1% higher HbA1c, 30 % lower HOMA index of insulin
sensitivity, 20% lower Gutt's index of insulin sensitivity, and 100 unit higher
Stumvoll's index of beta-cell function. After adjustment for waist circumference
visceral adipose tissue was still significantly associated with glucose
intolerance and insulin resistance, whereas there was a trend towards inverse or
no associations with subcutaneous adipose tissue. After adjustment, a 1cm
increase in visceral adipose tissue was associated with ~5% lower insulin
sensitivity (p<=0.0004) and ~0.18mmol/l higher 2-hr glucose (p<=0.001).
CONCLUSION: Visceral and subcutaneous adipose tissue assessed by ultrasonography
are significantly associated with glucose metabolism, even after adjustment for
other measures of obesity.
PMID- 25849817
TI - Effect of kumquat (Fortunella crassifolia) pericarp on natural killer cell
activity in vitro and in vivo.
AB - Natural killer (NK) cells play a key role in innate immune defense against
infectious disease and cancer. A reduction of NK activity is likely to be
associated with increased risk of these types of disease. In this study, we
investigate the activation potential of kumquat pericarp acetone fraction (KP-AF)
on NK cells. It is shown to significantly increase IFN-gamma production and NK
cytotoxic activity in human KHYG-1 NK cells. Moreover, oral administration of KP
AF significantly improves both suppressed plasma IFN-gamma levels and NK
cytotoxic activity per splenocyte in restraint-stressed mice. These results
indicate that raw kumquat pericarp activates NK cells in vitro and in vivo. To
identify the active constituents, we also examined IFN-gamma production on KHYG-1
cells by the predicted active components. Only beta-cryptoxanthin increased IFN
gamma production, suggesting that NK cell activation effects of KP-AF may be
caused by carotenoids such as beta-cryptoxanthin.
PMID- 25849816
TI - Less pollen-mediated gene flow for more signatures of glacial lineages: congruent
evidence from balsam fir cpDNA and mtDNA for multiple refugia in eastern and
central North America.
AB - The phylogeographic structure and postglacial history of balsam fir (Abies
balsamea), a transcontinental North American boreal conifer, was inferred using
mitochondrial DNA (mtDNA) and chloroplast DNA (cpDNA) markers. Genetic structure
among 107 populations (mtDNA data) and 75 populations (cpDNA data) was analyzed
using Bayesian and genetic distance approaches. Population differentiation was
high for mtDNA (dispersed by seeds only), but also for cpDNA (dispersed by seeds
and pollen), indicating that pollen gene flow is more restricted in balsam fir
than in other boreal conifers. Low cpDNA gene flow in balsam fir may relate to
low pollen production due to the inherent biology of the species and populations
being decimated by recurrent spruce budworm epidemics, and/or to low dispersal of
pollen grains due to their peculiar structural properties. Accordingly, a
phylogeographic structure was detected using both mtDNA and cpDNA markers and
population structure analyses supported the existence of at least five
genetically distinct glacial lineages in central and eastern North America. Four
of these would originate from glacial refugia located south of the Laurentide ice
sheet, while the last one would have persisted in the northern Labrador region.
As expected due to reduced pollen-mediated gene flow, congruence between the
geographic distribution of mtDNA and cpDNA lineages was higher than in other
North American conifers. However, concordance was not complete, reflecting that
restricted but nonetheless detectable cpDNA gene flow among glacial lineages
occurred during the Holocene. As a result, new cpDNA and mtDNA genome
combinations indicative of cytoplasmic genome capture were observed.
PMID- 25849818
TI - Organoselenium-catalyzed, hydroxy-controlled regio- and stereoselective amination
of terminal alkenes: efficient synthesis of 3-amino allylic alcohols.
AB - An efficient route to prepare 3-amino allylic alcohols in excellent regio- and
stereoselectivity in the presence of bases by orangoselenium catalysis has been
developed. In the absence of bases alpha,beta-unsaturated aldehydes were formed
in up to 97% yield. Control experiments reveal that the hydroxy group is crucial
for the direct amination.
PMID- 25849819
TI - Projected effect of increased active travel in German urban regions on the risk
of type 2 diabetes.
AB - BACKGROUND: Future transportation policy is likely to reduce emissions in the
cities and urban regions by strengthening active travel. Increased walking and
cycling are known to have positive effects on health outcomes. This work
estimates effects of increased active travel on type 2 diabetes in Germany, where
64% of the population live in urban regions. METHODS: Based on the effect size of
an increased active travel scenario reported from a recent meta-analysis, we
project the change in the life time risk, the proportion of prevented cases and
the change in diabetes free life time in a German birth cohort (born 1985)
compared to business as usual. RESULTS: The absolute risk reduction of developing
type 2 diabetes before the age of 80 is 6.4% [95% confidence interval: 3.7-9.7%]
for men and 4.7% [2.2-7.7%] for women, respectively. Compared to business as
usual, the increased active travel scenario prevents 14.0% [8.1-21.2%] of the
future cases of diabetes in men and 15.8% [9.3-23.1%] in women. Diabetes free
survival increases by 1.7 [1.0-2.7] years in men and 1.4 [0.6-2.3] in women.
CONCLUSIONS: Our projection predicts a substantial impact of increased active
travel on the future burden of type 2 diabetes. The most striking effect may be
seen in the number of prevented cases. In all urban regions with an increased
active travel transport policy, about one out of seven male and one out of six
female cases can be prevented.
PMID- 25849821
TI - Revision of biological methods for determination of EDC presence and their
endocrine potential.
AB - Endocrine-disrupting compounds (EDC) are chemicals responsible for disturbances
in the hormonal balance of organisms. This group of chemicals includes both
egzogenic and endogenic substances or their mixtures that impact functioning of
natural hormones in organisms. In the available literature one can find
information on the application of chromatographic and related techniques in the
analysis of environmental samples for detection, identification, and quantitation
of a wide spectrum of chemicals posing endocrine properties. On the other hand,
more and more biotests are being developed to determine endocrine potency of
environmental samples due to development of genetic engineering methods and
specific detection methods of cells' response to the action of particular
chemicals of interest. This article presents revisions of the most novel methods
for this potency determination with application to biological elements.
PMID- 25849822
TI - Application of gas chromatography to analysis of spirit-based alcoholic
beverages.
AB - Spirit-based beverages are alcoholic drinks; their production processes are
dependent on the type and origin of raw materials. The composition of this
complex matrix is difficult to analyze, and scientists commonly choose gas
chromatography techniques for this reason. With a wide selection of extraction
methods and detectors it is possible to provide qualitative and quantitative
analysis for many chemical compounds with various functional groups. This article
describes different types of gas chromatography techniques and their most
commonly used associated extraction techniques (e.g., LLE, SPME, SPE, SFE, and
SBME) and detectors (MS, TOFMS, FID, ECD, NPD, AED, O or EPD). Additionally,
brief characteristics of internationally popular spirit-based beverages and
application of gas chromatography to the analysis of selected alcoholic drinks
are presented.
PMID- 25849823
TI - Chromatographic methods for analysis of triazine herbicides.
AB - Gas chromatography (GC) and high-performance liquid chromatography (HPLC) coupled
to different detectors, and in combination with different sample extraction
methods, are most widely used for analysis of triazine herbicides in different
environmental samples. Nowadays, many variations and modifications of extraction
and sample preparation methods such as solid-phase microextraction (SPME), hollow
fiber-liquid phase microextraction (HF-LPME), stir bar sportive extraction
(SBSE), headspace-solid phase microextraction (HS-SPME), dispersive liquid-liquid
microextraction (DLLME), dispersive liquid-liquid microextraction based on
solidification of floating organic droplet (DLLME-SFO), ultrasound-assisted
emulsification microextraction (USAEME), and others have been introduced and
developed to obtain sensitive and accurate methods for the analysis of these
hazardous compounds. In this review, several analytical properties such as
linearity, sensitivity, repeatability, and accuracy for each developed method are
discussed, and excellent results were obtained for the most of developed methods
combined with GC and HPLC techniques for the analysis of triazine herbicides.
This review gives an overview of recent publications of the application of GC and
HPLC for analysis of triazine herbicides residues in various samples.
PMID- 25849824
TI - "Why not stoichiometry" versus "Stoichiometry--why not?" Part II: GATES in
context with redox systems.
AB - Redox equilibria and titration play an important role in chemical analysis, and
the formulation of an accurate mathematical description is a challenge. This
article is devoted to static and (mainly) dynamic redox systems; the dynamic
systems are represented by redox titrations. An overview addresses earlier
approaches to static redox systems (redox diagram plots, including Pourbaix
diagrams) and to titration redox systems, thereby covering a gap in the
literature. After this short review, the generalized approach to electrolytic
systems (GATES) is introduced, with generalized electron balance (GEB) as its
inherent part within GATES/GEB. Computer simulation, performed according to
GATES/GEB, enables following the changes in potential and pH of the solution,
together with chemical speciation at each step of a titration, thus providing
better insight into this procedure. The undeniable advantages of GATES/GEB over
earlier approaches are indicated. Formulation of GEB according to two approaches
(I and II) is presented on the respective examples. A general criterion
distinguishing between non-redox and redox systems is presented. It is indicated
that the formulation of GEB according to Approach II does not need the knowledge
of oxidation degrees of particular elements; knowledge of the composition,
expressed by chemical formula of the species and its charge, is sufficient for
this purpose. Approach I to GEB, known also as the "short" version of GEB, is
applicable if oxidation degrees for all elements of the system are known
beforehand. The roles of oxidants and reductants are not ascribed to particular
components forming a system and to the species thus formed. This is the complete
opposite of earlier approaches to redox titrations, based on the stoichiometric
redox reaction, formulated for this purpose. GEB, perceived as a law of matter
conservation, is fully compatible with other (charge and concentration) balances
related to the system in question. The applicability of GATES/GEB in optimization
a priori of chemical analyses made with use of redox titration is indicated. The
article is illustrated with many examples of static and dynamic redox systems.
The related plots are obtained from calculations made according to iterative
computer programs. This way, GATES/GEB enables seeing details invisible in real
experiments.
PMID- 25849825
TI - Magnetic solid-phase extraction based on modified ferum oxides for enrichment,
preconcentration, and isolation of pesticides and selected pollutants.
AB - Recently, a simple, rapid, high-efficiency, selective, and sensitive method for
isolation, preconcentration, and enrichment of analytes has been developed. This
new method of sample handling is based on ferum oxides as magnetic nanoparticles
(MNPs) and has been used for magnetic solid-phase extraction (MSPE) of various
analytes from various matrices. This review focuses on the applications of
modified ferum oxides, especially modified Fe3O4 MNPs, as MSPE adsorbent for
pesticide isolation from various matrices. Further perspectives on MSPE based on
modified Fe3O4 for inorganic metal ions, organic compounds, and biological
species from water samples are also presented. Ferum(III) oxide MNPs (Fe2O3) are
also highlighted.
PMID- 25849826
TI - The level of residual dispersion variation and the power of differential
expression tests for RNA-Seq data.
AB - RNA-Sequencing (RNA-Seq) has been widely adopted for quantifying gene expression
changes in comparative transcriptome analysis. For detecting differentially
expressed genes, a variety of statistical methods based on the negative binomial
(NB) distribution have been proposed. These methods differ in the ways they
handle the NB nuisance parameters (i.e., the dispersion parameters associated
with each gene) to save power, such as by using a dispersion model to exploit an
apparent relationship between the dispersion parameter and the NB mean.
Presumably, dispersion models with fewer parameters will result in greater power
if the models are correct, but will produce misleading conclusions if not. This
paper investigates this power and robustness trade-off by assessing rates of
identifying true differential expression using the various methods under
realistic assumptions about NB dispersion parameters. Our results indicate that
the relative performances of the different methods are closely related to the
level of dispersion variation unexplained by the dispersion model. We propose a
simple statistic to quantify the level of residual dispersion variation from a
fitted dispersion model and show that the magnitude of this statistic gives hints
about whether and how much we can gain statistical power by a dispersion-modeling
approach.
PMID- 25849827
TI - Evaluation of genetic polymorphisms in clusterin and tumor necrosis factor-alpha
genes in South Indian individuals with pseudoexfoliation syndrome.
AB - PURPOSE: The aim of this study was to explore the potential association of
genetic variants across clusterin (CLU) and tumor necrosis factor-alpha (TNF
alpha) genes in South Indian individuals with pseudoexfoliation syndrome (PEXS)
and pseudoexfoliation glaucoma (PEXG). MATERIALS AND METHODS: A total of 523
individuals including 299 unrelated cases (150 PEXS and 149 PEXG) and 224 age-
and ethnically-matched healthy controls were recruited for genetic analysis. Six
single-nucleotide polymorphisms (SNPs) including, five CLU SNPs (rs11136000,
rs2279590, rs9331888, rs9331931, rs3087554) and one promoter SNP (rs1800629) of
TNF-alpha were genotyped in all study subjects. Genotyping of CLU SNPs were
performed using the TaqMan allelic discrimination assay while TNF-alpha SNP was
genotyped using polymerase chain reaction (PCR)-based restriction fragment length
polymorphism (RFLP) analysis. Association analysis was performed by determining
the distributions of genotype and allele frequencies, Hardy-Weinberg equilibrium,
and chi-square p values and odds ratios as implemented in the Golden Helix SNP &
Variation Suite (SVS). RESULTS: Five CLU SNPs did not show any significant
differences in allele frequencies between patients and control subjects
(rs3087554, p = 0.919, OR = 1.01, 95% CI: 0.77-1.33; rs2279590, p = 0.432, OR =
1.12, 95% CI: 0.84-1.51; rs9331931, p = 0.310, OR = 1.24, 95% CI: 0.81-1.89;
rs11136000, p = 0.072, OR = 1.31, 95% CI: 0.97-1.76; rs9331888, p = 0.911, OR =
1.01, 95% CI: 0.78-1.31). The investigation of TNF-alpha SNP established a
significant association with PEXS and PEXG (p = 0.042, OR = 0.61, 95% CI: 0.38
0.99). However, this association did not remain significant after Bonferroni
correction. CONCLUSIONS: Our data suggest that genetic variants in CLU and TNF
alpha genes do not play a major role in the development of PEXS and PEXG in the
South Indian population.
PMID- 25849828
TI - HIV-1 vaccines based on replication-competent Tiantan vaccinia protected Chinese
rhesus macaques from simian HIV infection.
AB - OBJECTIVE: To assess the efficacy of HIV vaccines constructed from replication
competent Tiantan vaccinia virus (rTV) alone or combined with DNA in protecting
Chinese rhesus macaques from homologous Simian/Human Immunodeficiency Virus
(SHIV)-CN97001 challenge. METHODS: The nef, gag, pol, and gp140 genes from strain
CRF07_BC HIV-1 CN54 were selected to construct an HIV vaccine using the rTV or
rTV/DNA vaccine. After vaccination, the vaccine and control groups were
intravenously challenged with SHIV-CN97001 (32 MID50). HIV-specific antibodies
and neutralizing antibodies, gp70 V1V2 binding antibodies, and cytotoxic T
lymphocyte responses were measured prospectively after vaccination with an ELISA,
a virus infectivity assay in TZM-bl cells, and ELISPOT assays, respectively.
Viral RNA was quantified after challenge with real-time reverse transcriptase-PCR
(RT-PCR), and protection efficacy was determined with an analysis of CD8
lymphocyte depletion in vivo. RESULTS: Both rTV and DNA/rTV vaccine groups
developed strong cellular and humoral responses against HIV-1 CN54 antigens,
including Gag and Env, and also developed significant and persistent anti-Env
antibodies and neutralizing antibodies after immunization. Both the rTV and
DNA/rTV groups were significantly protected against SHIV-CN97001 or displayed
lower viremia than the controls. After CD8 lymphocyte depletion, no viremia was
detectable in the vaccinated monkeys, but rebounded rapidly in the control
animals. Protection against infection correlated with vaccine-elicited
neutralizing antibodies specific for homologous HIV-1 viruses. CONCLUSION: An rTV
based HIV-1 vaccine, with or without a DNA primer, provided protection from SHIV
challenge in a macaque model. Replication-competent Tiantan vaccinia is a
promising vector and should enable advances in HIV-1 vaccine development.
PMID- 25849829
TI - Dolutegravir inhibits HIV-1 Env evolution in primary human cells.
AB - OBJECTIVE: In treatment-naive HIV-positive individuals, the integrase strand
transfer inhibitor dolutegravir (DTG) has not been associated with emergent drug
resistance mutations, neither against this drug nor against other antiretroviral
drugs that were used in combination with it. This is in contrast to all other
antiretroviral drugs tested so far, including the integrase strand-transfer
inhibitors raltegravir (RAL) and elvitegravir that can lead to treatment failure
with the emergence of drug-resistance mutations. DESIGN: These observations
suggest that DTG may provide an additional protection against resistance compared
to other drugs by decreasing HIV-1 genetic evolution. METHODS: Here, we tested
this hypothesis by measuring the genetic and amino-acid diversity of Env/gp160
from two HIV-1 primary isolates that were grown in the presence of increasing
concentrations of DTG or RAL over the course of 38-55 weeks. RESULTS: The results
show that treatment with DTG led to less HIV-1 genetic and amino-acid
diversification over time, as compared to treatment with RAL or the absence of
drug. CONCLUSION: These results may help to explain the absence of emergent
resistance mutations in treatment-naive individuals treated with DTG.
PMID- 25849830
TI - Human adipose tissue as a reservoir for memory CD4+ T cells and HIV.
AB - OBJECTIVE: The objective of this study is to determine whether adipose tissue
functions as a reservoir for HIV-1. DESIGN: We examined memory CD4(+) T cells and
HIV DNA in adipose tissue-stromal vascular fraction (AT-SVF) of five patients
[four antiretroviral therapy (ART)-treated and one untreated]. To determine
whether adipocytes stimulate CD4(+) T cells and regulate HIV production, primary
human adipose cells were cocultured with HIV-infected CD4(+) T cells. METHODS: AT
SVF T cells were studied by flow cytometry, and AT-SVF HIV DNA (Gag and Env) was
examined by nested PCR and sequence analyses. CD4(+) T-cell activation and HIV
production were measured by flow cytometry and ELISA. RESULTS: AT-SVF CD3(+) T
cells were activated (>60% CD69(+)) memory CD4(+) and CD8(+) T cells in
uninfected and HIV-infected persons, but the AT-SVF CD4(+)/CD8(+) ratio was lower
in HIV patients. HIV DNA (Gag and Env) was detected in AT-SVF of all five
patients examined by nested PCR, comparably to other tissues [peripheral blood
mononuclear cell (PBMC), lymph node or thymus]. In coculture experiments,
adipocytes increased CD4(+) T-cell activation and HIV production approximately
two to three-fold in synergy with gamma-chain cytokines interleukin (IL)-2, IL7
or IL15. These effects were mitigated by neutralizing antibodies against IL6 and
integrin-alpha1beta1. Adipocytes also enhanced T-cell viability. CONCLUSION:
Adipose tissues of ART-treated patients harbour activated memory CD4(+) T cells
and HIV DNA. Adipocytes promote CD4(+) T-cell activation and HIV production in
concert with intrinsic adipose factors. Adipose tissue may be an important
reservoir for HIV.
PMID- 25849831
TI - Association of microbial translocation biomarkers with clinical outcome in
controllers HIV-infected patients.
AB - BACKGROUND: A proportion of patients who spontaneously control viral load
(controllers) experienced clinical progression. We hypothesized that microbial
translocation would independently determine the rate of disease progression in
controllers. METHODS: sCD14, lipopolysaccharide-binding protein (LBP) and EndoCab
levels were assessed in 114 antiretroviral-naive patients with CD4(+) T cells
above 500 cells/MUl (including 63 controllers and 51 noncontrollers). The
independent predictive value of these markers on time to progression to the
combined endpoint of AIDS, non-AIDS event, initiation of combination
antiretroviral therapy (cART) or CD4(+) cell count less than 500 cells/MUl was
assessed using a Cox regression model. RESULTS: Most of the patients progressed
to a combined endpoint (60%). Clinical progression in controllers was
significantly lower than in noncontrollers (P = 0.02). Controllers with lower
than the median baseline CD4(+) T-cell count and higher than the median baseline
viral load, sCD14 and EndoCab levels had a worse prognosis (P < 0.0001, P =
0.007, P = 0.05 and P = 0.012), while noncontrollers with higher than the median
baseline LBP level also had a worse prognosis (P = 0.019). sCD14 and LBP
increased and EndoCab decreased over time [from baseline (median values: 1486,
17604 ng/ml and 68 MMU/ml, respectively, to the date of event or the last
determination (median values: 1663, 20230 ng/ml and 49 MMU/ml), respectively] in
controllers (P = 0.04, 0.08 and 0.0006, respectively). CONCLUSION: Microbial
translocation seems to be an important determinant of clinical progression in HIV
infected controllers independently of viremia. Measures to improve the intestinal
mucosa damage or decrease translocation could influence the outcome in these
patients.
PMID- 25849832
TI - Incomplete immune reconstitution despite virologic suppression in HIV-1 infected
children and adolescents.
AB - OBJECTIVES: Some perinatally infected children do not regain normal CD4(+) T-cell
counts despite suppression of HIV-1 plasma viremia by antiretroviral therapy
(ART). The frequency, severity and significance of these discordant treatment
responses remain unclear. DESIGN: We examined the persistence of CD4(+)
lymphocytopenia despite virologic suppression in 933 children (>= 5 years of age)
in the USA, Latin America and the Caribbean. METHODS: CD4(+) T-cell trajectories
were examined and Kaplan-Meier methods used to estimate median time to CD4(+) T
cell count at least 500 cells/MUl. RESULTS: After 1 year of virologic
suppression, most (99%) children achieved a CD4(+) T-cell count of at least 200
cells/MUl, but CD4(+) T-cell counts remained below 500 cells/MUl after 1 and 2
years of virologic suppression in 14 and 8% of children, respectively. Median
times to first CD4(+) T-cell count at least 500 cells/MUl were 1.29, 0.78 and
0.46 years for children with less than 200, 200-349 and 350-499 cells/MUl at the
start of virologic suppression. New AIDS-defining events occurred in nine
children, including four in the first 6 months of virologic suppression. Other
infectious and HIV-related diagnoses occurred more frequently and across a wide
range of CD4(+) cell counts. CONCLUSION: ART improved CD4(+) cell counts in most
children, but the time to CD4(+) cell count of at least 500 cells was highly
dependent upon baseline immunological status. Some children did not reach a
CD4(+) T-cell count of 500 cells/MUl despite 2 years of virologic suppression.
AIDS-defining events occurred in 1% of the population, including children in whom
virologic suppression and improved CD4(+) T-cell counts were achieved.
PMID- 25849833
TI - Risk of progression to high-grade anal intraepithelial neoplasia in HIV-infected
MSM.
AB - OBJECTIVE: To assess the value of several factors to predict the risk of
progression to high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of
HIV-infected MSM. DESIGN: Longitudinal study of 556 HIV-infected MSM who
underwent screening for anal dysplasia (include anal cytology and high-resolution
anoscopy at each visit). METHODS: Progression rate to HGAIN was estimated by
Kaplan-Meier analysis. Predictors of progression were assessed by Cox
proportional hazards regression. RESULTS: Sixty-eight incidents HGAIN cases over
649 person-years of follow-up were diagnosed, resulting in a progression rate of
10.5 cases/100 person-years [95% confidence interval (CI), 8.1-13.3). The
cumulative incidence of HGAIN was 7.2% at 12 months (95% CI, 4.3-10.1) and 16.2%
at 24 months (95% CI, 11.7-20.7). Independent risk factors for progression were
as follows: abnormal cytology [hazard ratio (HR), 2.5 (95% CI, 1.2-4.9) if low
grade squamous intraepithelial lesion, HR 2.76 (95% CI, 1.4-5.3) if atypical
squamous cells of uncertain significance and HR 7.73 (95% CI, 2.3-25.4) if high
grade squamous intraepithelial lesion], abnormal high-resolution anoscopy (HR
3.57; 95% CI, 2-6.4) and infection by 16 or 18 human papillomavirus (HR 1.63; 95%
CI, 1-2.6). To be receiving HAART (HR 0.4; 95% CI, 0.2-0.7) and have stable
sexual couple (HR 0.62; 95% CI, 0.4-0.9) were protective factors. Patients with
favorable predictors had an incident rate of 2.86 cases/100 person-years (95% CI,
3.5-10.3). CONCLUSION: The rate of progression to HGAIN varies according to
different predictors that should be considered when assessing the particular risk
of each patient. Patients with low risk of progression could be screened at
longer intervals. BRIEF SUMMARY: We describe the risk of progression to HGAIN in
a cohort of 556 HIV-infected MSM. The incidence rate of HGAIN varies widely
according to different predictors. These factors should be considered when
assessing the particular risk of each patient.
PMID- 25849834
TI - Effects of HIV and combination antiretroviral therapy on cortico-striatal
functional connectivity.
AB - OBJECTIVE: Determine whether HIV and combination antiretroviral therapy (cART)
affect resting-state functional connectivity (rs-fc) between the striatum and the
cortical regions. METHODS: Forty-nine HIV-uninfected (HIV-) and 132 HIV-infected
(HIV+) (65% receiving cART) patients underwent laboratory studies (current and
nadir CD4 T-cell counts, and plasma HIV viral load), neuropsychological
performance testing, and neuroimaging. Rs-fc, which examines the coordination of
neural activity in distant brain regions, was used to investigate the cortico
striatal functional connections. The effect of cART was assessed comparing HIV+
individuals on cART (HIV+/cART+), and HIV+ individuals not currently receiving
cART (HIV+/cART-). Relationships between laboratory tests, cognitive performance,
and cART on subcortical-cortical rs-fc were assessed by an analysis of variance.
RESULTS: HIV+ individuals had lower cortico-striatal functional connectivity than
HIV- controls, specifically between the striatum and the default mode network (P
< 0.001) and ventral attention network (P < 0.001). HIV+/cART+ individuals had
higher functional connectivity between the striatum, and default mode network (P
= 0.02) and ventral attention network (P = 0.01), compared to the HIV+/cART-
patients. Laboratory (current and nadir CD4 T-cell counts, plasma viral load) and
neuropsychological performance was not correlated with cortico-striatal rs-fc.
CONCLUSIONS: HIV was associated with disrupted cortico-striatal networks,
consistent with HIV's known impact on the subcortical areas. Interestingly,
within certain networks, HIV+/cART+ individuals had similar rs-fc compared to HIV
controls, suggesting possible improvements in HIV-related neural dysfunction due
to medications. Rs-fc may be a sensitive biomarker of neural insult and its
recovery following cART. Additional studies may show rs-fc has utility in
measuring acute inflammation caused by HIV.
PMID- 25849836
TI - Estimating the range of potential epidemiological impact of pre-exposure
prophylaxis: run-away success or run-away failure?
AB - OBJECTIVE: To investigate the influence of potential interactions between key
aspects of a pre-exposure prophylaxis (PrEP) intervention on projections of
epidemiological impact and cost-effectiveness. METHODS: A mathematical model
representing the HIV epidemic and intervention context in Nyanza province in
Kenya was developed. We consider a scenario whereby a fixed annual budget is
allocated to a PrEP intervention. A standard projection of impact is generated,
assuming that the unit cost of PrEP, adherence to PrEP and the ability of the
programme to direct PrEP to those at high risk, all stay constant. The influence
of dynamic assumptions and possible interactions between PrEP intervention
assumptions is then assessed in comparison. RESULTS: The cumulative impact of a
PrEP intervention could be increased approximately two-fold, relative to the
standard projection, if positive interactions (between coverage and cost,
coverage and adherence, prioritization and time) are assumed, whereas negative
interactions between these factors could almost entirely negate the preventive
benefit of the PrEP intervention. The corresponding estimates of cost per
infection averted span a wide range from $2060 to $36360. CONCLUSIONS: Multiple
potentially interacting factors will determine the impact of PrEP. Model
forecasts should reflect that uncertainty and programmes should focus on these
factors and measure them, to maximize the impact of programmes.
PMID- 25849835
TI - High HIV prevalence and incidence among MSM across 12 cities in India.
AB - OBJECTIVE: To characterize prevalence, incidence, and associated correlates of
HIV infection among MSM in 12 cities across India. DESIGN: Cross-sectional sample
using respondent-driven sampling from September 2012 to June 2013. METHODS: A
total 12022 MSM (~1000/city) were recruited. Participants had to be at least 18
years, self-identify as male, and report oral/anal intercourse with a man in the
prior year. HIV infection was diagnosed using three rapid tests. Cross-sectional
HIV incidence was estimated using a multiassay algorithm. All estimates
incorporate respondent-driven sampling-II weights. RESULTS: Median age was 25
years, 45% self-identified as 'panthi' (predominantly penetrative anal
intercourse) and 30.6% reported being married to a woman. Weighted HIV prevalence
was 7.0% (range: 1.7-13.1%). In multivariate analysis, significantly higher odds
of HIV infection was observed among those who were older, had lower educational
attainment, were practicing purely receptive anal sex or both receptive and
penetrative sex, and those who were herpes simplex virus-2 positive. Of 1147 MSM
who tested HIV positive, 53 were identified as recent HIV infections (annualized
incidence = 0.87%; range = 0-2.2%). In multivariate analysis, injecting drugs in
the prior 6 months, syphilis, and higher number of male partners and fewer female
partners were significantly associated with recent HIV infection. CONCLUSION: We
observed a high burden of HIV among MSM in India with tremendous diversity in
prevalence, incidence, and risk behaviors. In particular, we observed high
incidence in areas with relatively low prevalence suggesting emerging epidemics
in areas not previously recognized to have high HIV burden.
PMID- 25849837
TI - Human papilloma virus vaccination induces strong human papilloma virus specific
cell-mediated immune responses in HIV-infected adolescents and young adults.
AB - The ability of a quadrivalent human papilloma virus (HPV)-16/18/6/11 virus-like
particles vaccine (Gardasil) to elicit HPV-specific cell-mediated immune
responses was evaluated in antiretroviral therapy (ART)-treated HIV-infected
young adults. Results showed that, after three doses of vaccine, central memory
and effector memory CD4(+) and CD8(+) T lymphocytes, as well as HPV-specific
interleukin (IL)2(+)/CD4(+), interferon-gamma (IFN-gamma(+))/CD4(+), IFN
gamma(+)/CD8(+) and tumour necrosis factor-alpha (TNF-alpha)(+)/CD8(+) T
lymphocytes and Perforin and Granzyme B secreting CD8(+) T lymphocytes were
significantly increased. Notably, results obtained in HIV-infected patients were
comparable to those seen in HIV-uninfected age-matched healthy controls.
PMID- 25849838
TI - Protein-losing enteropathy in an HIV-infected pediatric patient with previous
disseminated Mycobacterium genavense infection.
PMID- 25849839
TI - Proximal tubular dysfunction in a HIV-1 patient with coadministered tenofovir
disoproxil-fumarate and ibuprofen.
PMID- 25849840
TI - Management guidelines for non-AIDS morbidity result in increased screening but no
change in primary prevention implementation.
PMID- 25849841
TI - Response to: The relationship of physical performance with HIV disease and
mortality: a cohort study.
PMID- 25849842
TI - The relationship of physical performance with HIV disease and mortality: authors'
response.
PMID- 25849843
TI - Retention in care for HIV-infected patients in the eye of the Ebola storm:
lessons from Monrovia, Liberia.
PMID- 25849844
TI - Can yeast isolation be predicted in complicated secondary non-postoperative intra
abdominal infections?
AB - INTRODUCTION: The aim of this study was to create a predictive score for yeast
isolation in patients with complicated non-postoperative intra-abdominal
infections (CNPIAI) and to evaluate the impact of yeast isolation on outcome.
METHODS: All patients with a CNPIAI undergoing emergency surgery over a three
year period were included in the retrospective cohort (RC, n = 290). Patients
with a yeast-positive peritoneal fluid culture (YP) were compared with patients
with a yeast-negative culture (YN). Multivariate logistic regression was used to
identify factors independently associated with yeast isolation and a predictive
score was built. The score's performance was then established in the prospective
cohort (PC, n = 152) over an 18-month period. Outcome of the whole cohort was
evaluated and independent risks factors of mortality searched. RESULTS: In the
RC, 39 patients (13.4%) were YP. Four factors were independently associated with
the YP group: length of stay before surgery >=48 h (odds ratio (OR) (95%
confidence interval (CI)) = 3.1 (1.4 to 6.9), P = 0.004, 1 point), per-operative
cardiovascular failure (2.4 (1.1 to 5.8), P = 0.04, 1 point), generalized
peritonitis (6.8 (2.7 to 16.7), P <0.001, 2 points) and upper gastrointestinal
tract perforation (2.5 (1.2 to 5.6), P = 0.02, 1 point). In the PC, the area
under the curve (95%CI) of the predictive score's receiver operating
characteristic curve was 0.79 (0.72 to 0.86). For predicting an intra-abdominal
candidiasis (IAC), a score >=3 had a sensitivity of 0.60, a specificity of 0.84,
a positive predictive value of 0.49 and a negative predictive value of 0.89.
Furthermore, yeast isolation was associated with worse outcome and independently
associated with mortality in the whole cohort (OR = 2.15; 95%CI (1.03 to 4.46), P
= 0.04). CONCLUSIONS: The new predictive score can be used to rule out intra
abdominal candidiasis and thus avoid the initiation of antifungal treatment. It
is suited to less severe infections than previously published scores. IAC is
associated independently with an increased mortality in this population.
PMID- 25849845
TI - Effect of arsenite on nitrosative stress in human breast cancer cells and its
modulation by flavonoids.
AB - Arsenic (As) is used in the treatment of leukemia and breast cancer due to its
oxidative cytotoxic action. However, it is also toxic to normal cells. One
proposed anticancer mechanism induced by As might be nitrosative stress (NS). It
is believed that antioxidant flavonoids in combination with As might reduce its
toxic action on normal cells without interfering with its antitumor action. In
the present study, we evaluated the antineoplastic potential of As on breast
human cancer lines MCF-7 and ZR-75-1 treated with redox-modulating flavonoids,
such as quercetin (Q) and silymarin (S). Even though both cell lines differed
about their oxidative responsiveness, their viability was decreased by NS
induction through gamma-glutamyltranspeptidase inhibition. Arsenic triggered NS
in both MCF-7 and ZR-75-1 cultures, with the formers more sensitive without
recovering their pre-treatment capacity. ZR-75-1 cells maintained their
antioxidant status, whereas MCF-7 ones treated with S, As, and As + Q did not.
Silymarin did not interfere with the described As bioactivity. NS was an
anticancer mechanism exerted by As depending on the redox cellular response that
could be differentially modified by dietary antioxidants. Hence, it is worthwhile
to consider the use of dietary antioxidants as adjuvant in cancer chemotherapy,
especially when using As.
PMID- 25849846
TI - Presence of circulating Her2-reactive CD8 + T-cells is associated with lower
frequencies of myeloid-derived suppressor cells and regulatory T cells, and
better survival in older breast cancer patients.
AB - INTRODUCTION: Breast cancer is one of the most common cancers among women. Its
incidence is increasing in many countries and a higher number of older women are
now being diagnosed with the disease. Immune parameters are implicated in disease
progression, and the frequencies of both myeloid-derived suppressor cells (MDSCs)
and regulatory T cells (Tregs), associated with tumour burden, have been
suggested to be indicators of poor prognosis in cases of metastatic breast
cancer. METHODS: Here, we have assessed the frequency of peripheral Tregs and
MDSCs in relation to in vitro T cell responses to Her2 antigen in 40 untreated
breast cancer patients 65 to 87 years of age at diagnosis. RESULTS: The five-year
survival rate of patients who mounted a CD8+ T cell response to Her2 peptides and
had a lower frequency of Lin-CD14+HLA-DR-MDSCs was 100% compared to only 38% in
patients without Her2-reactive CD8+ T cells and with higher frequencies of MDSCs
(P = 0.03). Patients who lacked a CD8 response to Her2 tended to have higher
frequencies of MDSCs. Similarly, patients who lacked a CD8 response to Her2 and
had higher frequencies of CD4+Foxp3+CD127lowCD25+ Tregs had only 50% survival
compared to the 100% survival of patients who did mount a CD8 response and had
lower frequencies of Tregs (P = 0.03). A similar trend was observed for activated
(CD4+CD45RA-Foxp3hi) but not resting Tregs (CD4+CD45RA+FoxP3+). This survival
advantage was observed in both metastatic and non-metastatic patients.
CONCLUSIONS: Our data demonstrate a negative role of both MDSCs and Tregs in the
prognosis of breast cancer patients, the mechanism of which might be through
dampening favourable CD8+ T cell immune responses to tumour-associated antigens.
PMID- 25849847
TI - Parent-reported symptoms of acute otitis media during the first year of life:
what is beneath the surface?
AB - BACKGROUND: Most estimates of the incidence of acute otitis media (AOM) are based
on general practitioner (GP) or pediatrician diagnoses. It is likely that these
figures underestimate the community incidence of AOM since parents do not visit
their doctor every time their child suffers from acute ear symptoms. The impact
of these symptom episodes may be substantial since they affect the child's
quality of life and parents' productivity. METHODS: To determine AOM symptoms in
the community, we measured parent-reported AOM symptoms daily for 12 consecutive
months in 1,260 children participating in a prospective birth cohort in the
Netherlands. The mean age of these children was at study enrollment 0.9 months
(standard deviation 0.6). A parent-reported AOM symptom episode was defined as
fever (temperature 38C or above) plus at least one of the following symptoms: ear
pain and ear discharge. These febrile AOM symptom episodes were linked to GP
consultations and diagnoses in the GP electronic health records. RESULTS: With an
estimated 624 parent-reported symptom episodes per 1,000 child-years (95% CI: 577
to 674) incidence of febrile AOM symptoms during the child's first year is high.
The GP was consulted in half of these symptom episodes and AOM was diagnosed in
49% of these consultations. CONCLUSIONS AND RELEVANCE: The incidence of febrile
AOM symptoms in the first year of life is high in Dutch children and leads to a
GP-consultation in only half of the cases. This suggests that AOM symptomatology
in the community is underestimated when focusing on GP-diagnosed AOM episodes
alone, since a considerable proportion of febrile AOM symptom episodes are
treated symptomatically by parents at home and do not come to the attention of
the GP. Having data on community AOM symptomatology available for each country is
important when the potential impact of preventive and therapeutic interventions
for AOM are studied.
PMID- 25849848
TI - Iron(III) complexes of a pyridoxal Schiff base for enhanced cellular uptake with
selectivity and remarkable photocytotoxicity.
AB - Iron(III) complexes of pyridoxal (vitamin B6, VB6) or salicylaldehyde Schiff
bases and modified dipicolylamines, namely, [Fe(B)(L)](NO3) (1-5), where B is
phenyl-N,N-bis((pyridin-2-yl)methyl)methanamine (phbpa in 1), (anthracen-9-yl)
N,N-bis((pyridin-2-yl)methyl)methanamine (anbpa in 2, 4) and (pyren-1-yl)-N,N
bis((pyridin-2-yl)methyl)methanamine (pybpa in 3, 5) (H2L(1) is 3-hydroxy-5
(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridine (1-3) and
H2L(2) is 2-[(2-hydroxyphenyl-imino)methyl]phenol), were prepared and their
uptake in cancer cells and photocytotoxicity were studied. Complexes 4 and 5,
having a non-pyridoxal Schiff base, were prepared to probe the role of the
pyridoxal group in tumor targeting and cellular uptake. The PF6 salt (1a) of
complex 1 is structurally characterized. The complexes have a distorted six
coordinate FeN4O2 core where the metal is in the +3 oxidation state with five
unpaired electrons. The complexes display a ligand to metal charge transfer band
near 520 and 420 nm from phenolate to the iron(III) center. The photophysical
properties of the complexes are explained from the time dependent density
functional theory calculations. The redox active complexes show a quasi
reversible Fe(III)/Fe(II) response near -0.3 V vs saturated calomel electrode.
Complexes 2 and 3 exhibit remarkable photocytotoxicity in various cancer cells
with IC50 values ranging from 0.4 to 5 MUM with 10-fold lower dark toxicity. The
cell death proceeded by the apoptotic pathway due to generation of reactive
oxygen species upon light exposure. The nonvitamin complexes 4 and 5 display 3
fold lower photocytotoxicity compared to their VB6 analogues, possibly due to
preferential and faster uptake of the vitamin complexes in the cancer cells.
Complexes 2 and 3 show significant uptake in the endoplasmic reticulum, while
complexes 4 and 5 are distributed throughout the cells without any specific
localization pattern.
PMID- 25849849
TI - Patterned Carboxylation of Graphene Using Scanning Electrochemical Microscopy.
AB - A simple, direct, and versatile scanning electrochemical microscopy (SECM)
approach for local carboxylation of multilayered graphene on nickel is
demonstrated, in which carbon dioxide serves as the carboxylation agent under
reductive conditions in N,N-dimethylformamide. The use of SECM gives control over
both the spatial dimensions and the degree of carboxylation. While the pattern
size, in general, is governed by the dimension of the SECM tip, the degree of
modification, expressed as the surface coverage of carboxylate groups introduced
at the graphene substrate, is found to be controlled by the electrolysis time.
This is supported by electrochemical measurements, two-dimensional X-ray
photoelectron spectroscopy, Raman spectroscopy mapping, and He ion microscopy.
Surprisingly, intercalation of the supporting electrolyte in the multilayered
graphene on nickel occurs to a relatively small extent when compared to
corresponding results obtained in previously described carboxylations of this
kind of multilayered graphene.
PMID- 25849850
TI - Rapid decrease in salivary epidermal growth factor levels in patients with
Sjogren's syndrome: A 3-year follow-up study.
AB - OBJECTIVES: To assess changes in salivary epidermal growth factor (EGF) levels
within three years and investigate the correlation between these changes and the
severity of intraoral manifestations in patients with Sjogren's syndrome (SS).
METHODS: Twenty-three SS patients (14 primary SS and 9 secondary SS) and 14
controls were followed up for three years. Salivary EGF concentration was
measured using an enzyme-linked immunosorbent assay, and intraoral manifestations
were evaluated using a short version of the Oral Health Impact Profile (OHIP-14).
Changes in salivary flow rate, EGF level, and severity of intraoral
manifestations were analyzed, along with associations among them. RESULTS: The
OHIP-14 score significantly increased and the total salivary EGF output
significantly decreased after three years in the SS group (10.2 +/- 8.8 vs. 12.6
+/- 9.2, p = 0.040; 10158.4 +/- 9820.9 vs. 8352.8 +/- 7813.3 pg/10 min, p =
0.032), though the salivary flow rate did not change. The decrease in total EGF
output was especially high in patients with long disease duration and poor oral
health-related quality of life (OHRQoL). In patients with poor OHRQoL, the change
in total EGF output significantly correlated with the OHIP-14 score (r = - 0.847,
p = 0.008). However, there was no correlation between the change in salivary flow
rate and the OHIP-14 score. CONCLUSIONS: The rapid decrease in salivary EGF level
contributes to the progression of intraoral manifestations of SS.
PMID- 25849851
TI - Utility of ferritin as a predictor of the patients with Kawasaki disease
refractory to intravenous immunoglobulin therapy.
AB - OBJECTIVES: The aim of this study is to investigate whether ferritin can be a
useful marker for the prediction of the patients with Kawasaki disease (KD)
refractory to initial intravenous immunoglobulin (IVIG) therapy. METHODS: This
retrospective study enrolled 85 patients with KD hospitalized at Kitakyushu
General Hospital during 2010-2014. These patients were divided into IVIG
responders (n = 57) and non-responders (n = 28). Serum ferritin levels and the
scoring systems for the prediction of non-responsiveness to initial IVIG therapy
were compared between these two groups. RESULTS: Serum ferritin level was
significantly elevated in non-responders (p = 0.010). The area under the receiver
operating characteristics curve was 0.674, and the sensitivity and specificity in
more than 165 ng/ml of serum ferritin level were 70.4% and 63.2%, respectively.
In two of the three prediction scoring systems, non-responders also showed
significantly higher scores than responders, but many non-responders had low
scores of these scoring systems. More than half of the patients with a low score
of these scoring systems had high serum ferritin level (>= 165 ng/ml).
CONCLUSIONS: Serum ferritin level might be a useful marker for the prediction of
non-responsiveness to initial IVIG therapy and could be an important
complementary marker to the prediction scoring systems.
PMID- 25849852
TI - Systemic sclerosis and risk of venous thromboembolism: A systematic review and
meta-analysis.
AB - BACKGROUND: Several chronic inflammatory disorders, such as rheumatoid arthritis,
inflammatory myositis, and systemic vasculitides, have been linked to an
increased risk of venous thromboembolism (VTE). However, the data on systemic
sclerosis (SSc) remains unclear. METHODS: We conducted a systematic review and
meta-analysis of observational studies that reported odds ratio, relative risk,
hazard ratio, or standardized incidence ratio comparing risk of VTE in patients
with SSc versus non-SSc participants. Pooled risk ratio and 95% confidence
intervals (CIs) were calculated using a random-effect, generic inverse variance
method of DerSimonian and Laird. RESULTS: Out of 776 potentially relevant
articles, five eligible studies were identified and included in the data
analysis. The pooled risk ratio of VTE in patients with SSc was 2.51 (95% CI,
1.79-3.54). The statistical heterogeneity of this study was high with an I2 of
90%. CONCLUSIONS: Our study demonstrated a statistically significant increased
VTE risk among patients with SSc.
PMID- 25849853
TI - The effect of isokinetic and aerobic exercises on serum interleukin-6 and tumor
necrosis factor alpha levels, pain, and functional activity in patients with knee
osteoarthritis.
AB - OBJECTIVES: The aim of this study is to investigate the effects of isokinetic and
aerobic exercise training programs on serum pro-inflammatory cytokine levels,
pain, and functional activity in patients with knee osteoarthritis (OA). METHODS:
Forty-two postmenopausal women and men with knee OA according to American College
of Rheumatology diagnostic criteria were included. Patients were randomized into
isokinetic and aerobic exercises and control groups. In intervention groups,
patients were included in predetermined exercise programs 3 times per week for 6
weeks. Severity of pain, functional activity status, muscle strength, functional
capacity, and serum cytokine levels were evaluated at baseline and at the 6th
week. RESULTS: At the end of 6th week, there was no statistically significant
decrease in serum pro-inflammatory cytokine levels in both the exercise groups,
although C-reactive protein levels exhibited a strong trend toward significance.
We found a significant decrease in visual analog scale and Western Ontario
McMaster Osteoarthritis Index scores, and significant increase in functional
capacity and muscle strength in both the exercise groups compared with those in
the control group.
PMID- 25849854
TI - TAp63gamma and DeltaNp63beta promote osteoblastic differentiation of human
mesenchymal stem cells: regulation by vitamin D3 Metabolites.
AB - The transcription factor p63 is required for skeletal formation, and is important
for the regulation of 1alpha,25(OH)2D3 receptor (VDR) in human mesenchymal stem
cells (hMSC). Herein we report that TAp63gamma and DeltaNp63beta appear to be an
integral part of the osteoblastic differentiation of hMSC and are differentially
regulated by the vitamin D3 metabolites 1alpha,25(OH)2D3 and 24R,25(OH)2D3. We
compared the endogenous expression of p63 isoforms (TA- and DeltaNp63) and splice
variants (p63alpha, -beta, -gamma), in naive hMSC and during osteoblastic
differentiation of hMSC. TAp63alpha and -beta were the predominant p63 variants
in naive, proliferating hMSC. In contrast, under osteoblastic differentiation
conditions, expression of p63 changed from the TAp63alpha and -beta to the
TAp63gamma and DeltaNp63beta variants. Transient overexpression of the p63
variants demonstrated that TAp63beta, DeltaNp63beta, and DeltaNp63gamma increased
alkaline phosphatase activity and DeltaNp63alpha and -gamma increased the
expression of mRNA for osteocalcin and osterix. Our results support the
hypothesis that TAp63alpha and -beta promote a naive state in hMSC. Moreover,
TAp63gamma is increased during and promotes early osteoblastic differentiation
through the expression of pro-osteogenic genes; VDR, Osterix, Runx2 and
Osteopontin. DeltaNp63beta also appears to support osteogenic maturation through
increased alkaline phosphatase activity. Treatment with 1alpha,25(OH)2D3
increased the expression of mRNA for DeltaNp63, while addition of 24R,25(OH)2D3
increased the expression of TA- and DeltaNp63gamma variants. These novel findings
demonstrate for the first time that p63 variants are differentially expressed in
naive hMSC (TAp63alpha,beta), are important during the osteoblastic
differentiation of hMSC (TAp63gamma and DeltaNp63beta), and are differentially
regulated by the vitamin D3 metabolites, 1alpha,25(OH)2D3 and 24R,25(OH)2D3. The
molecular nuances and mechanisms of osteoblastic differentiation presented here
will hopefully improve our understanding of bone development, complications in
bone repair (mal- and non-union fractures), osteoporosis and possibly lead to new
modalities of treatment.
PMID- 25849855
TI - Multi-locus analysis of genomic time series data from experimental evolution.
AB - Genomic time series data generated by evolve-and-resequence (E&R) experiments
offer a powerful window into the mechanisms that drive evolution. However,
standard population genetic inference procedures do not account for sampling
serially over time, and new methods are needed to make full use of modern
experimental evolution data. To address this problem, we develop a Gaussian
process approximation to the multi-locus Wright-Fisher process with selection
over a time course of tens of generations. The mean and covariance structure of
the Gaussian process are obtained by computing the corresponding moments in
discrete-time Wright-Fisher models conditioned on the presence of a linked
selected site. This enables our method to account for the effects of linkage and
selection, both along the genome and across sampled time points, in an
approximate but principled manner. We first use simulated data to demonstrate the
power of our method to correctly detect, locate and estimate the fitness of a
selected allele from among several linked sites. We study how this power changes
for different values of selection strength, initial haplotypic diversity,
population size, sampling frequency, experimental duration, number of replicates,
and sequencing coverage depth. In addition to providing quantitative estimates of
selection parameters from experimental evolution data, our model can be used by
practitioners to design E&R experiments with requisite power. We also explore how
our likelihood-based approach can be used to infer other model parameters,
including effective population size and recombination rate. Then, we apply our
method to analyze genome-wide data from a real E&R experiment designed to study
the adaptation of D. melanogaster to a new laboratory environment with
alternating cold and hot temperatures.
PMID- 25849856
TI - Lung function, symptoms and inflammation during exacerbations of non-cystic
fibrosis bronchiectasis: a prospective observational cohort study.
AB - BACKGROUND: Exacerbations of non-cystic fibrosis bronchiectasis cause significant
morbidity but there are few detailed data on their clinical course and associated
physiological changes. The biology of an exacerbation has not been previously
described. METHODS: This was a prospective observational cohort study of 32
outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010
and August 2012. Patients completed a symptom diary card and measured their peak
expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic
treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow
at exacerbation were analysed, and further measurements including the COPD
Assessment Test (CAT) and inflammatory markers were also compared to baseline
values. RESULTS: At baseline, health status was significantly related to lung
function, prognostic severity and systemic inflammation. 51 exacerbations
occurred in 22 patients. Exacerbation symptoms began a median (interquartile
range) of 4 (2, 7) days before treatment started and the median exacerbation
duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation,
mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean
CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4
(2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011).
Exacerbations where PEFR fell by >=10% were longer with more symptoms at onset.
CONCLUSION: Exacerbations of non-CF bronchiectasis are inflammatory events, with
worsened symptoms, lung function and health status, and a prolonged recovery
period. Symptom diary cards, PEFR and CAT scores are responsive to changes at
exacerbation and may be useful tools for their detection and monitoring.
PMID- 25849857
TI - Biosensor enhancement using grooved micromixers: part I, numerical studies.
AB - In this study we examine the use of the staggered herringbone mixer (SHM) to
increase the efficiency of analyte delivery to a planar biosensor surface.
Although there has been an extensive amount of research regarding the
optimization of the SHM for mixing purposes, there has been very little work
regarding the use of said micromixers for sensing purposes. Here, we use
numerical methods to examine the effect of the SHM geometry on the efficiency of
analyte delivery to a biosensor surface. We show the level of sensing enhancement
of an SHM-based sensing chamber over that of an unmixed chamber has a strong
dependence on the SHM geometry, the Peclet number, and the overall sensor length.
The results presented herein are applicable to a very wide range of biosensor
transduction mechanisms and target analytes.
PMID- 25849858
TI - Contemporary Trends in the Ambulatory Surgical Treatment of Urolithiasis:
Population-Based Analysis.
AB - PURPOSE: To describe the utilization of shockwave lithotripsy (SWL) and
ureteroscopy (URS) in ambulatory surgery centers, as well as to identify patient
specific factors predictive of one procedure over the other. PATIENTS AND
METHODS: We evaluated the current trends in the use of SWL and URS in the
ambulatory settings over a 5-year period in the state of California using the
State of California Office of Statewide Health Planning and Development (OSHPD)
database. RESULTS: We identified 113,447 ambulatory kidney stone surgical
procedures including 64,632 SWL (57%) and 48,815 URS (43%) treatments in the
OSHPD database between 2005 and 2010. The total annual ambulatory stone surgeries
increased from 17,831 cases in 2005 to 18,933 cases in 2010 (P<0.001). Between
2005 and 2010, the use of URS increased significantly from 6978 (39%) cases in
2005 to 9259 (49%) cases in 2010 (P<0.0012), whereas the use of SWL decreased
from 10,853 (61%) cases in 2005 to 9674 (51%) cases in 2010 (P=0.0012). In
multivariate analysis, age >= 75 years (P<0.001), hypertension (P=0.025), and
obesity (P<0.001) all increased odds of undergoing URS. In addition, men
(P=0.013) and non-Medicaid patients (P<0.001) were more likely to undergo URS.
CONCLUSIONS: The use of URS increased significantly in the state of California
among patients undergoing urinary stone surgical procedures in the ambulatory
setting, while the use of SWL decreased between 2005 and 2010. Possible
explanations for these trends include improved URS stone-free rates, improved
cost-effectiveness of URS, and enhanced technology leading to increased use of
URS over SWL.
PMID- 25849859
TI - The anxiolytic effect of midazolam in third molar extraction: a systematic
review.
AB - PURPOSE: To assess the efficacy of midazolam for anxiety control in third molar
extraction surgery. METHODS: Electronic retrievals were conducted in Medline (via
PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12),
and the System for Information on Grey Literature in Europe (SIGLE). The
bibliographies of relevant clinical trials were also checked. Randomized
controlled trials satisfying the inclusion criteria were evaluated, with data
extraction done independently by two well-trained investigators. Disagreements
were resolved by discussion or by consultation with a third member of the review
team. RESULTS: Ten studies were included, but meta-analysis could not be
conducted because of the significant differences among articles. All but one
article demonstrated that midazolam could relieve anxiety. One article
demonstrated that propofol offered superior anxiolysis, with more rapid recovery
than with midazolam. Compared with lorazepam and diazepam, midazolam did not
distinctly dominate in its sedative effect, but was safer. Two articles used
midazolam in multidrug intravenous sedation and proved it to be more effective
than midazolam alone. CONCLUSION: It was found, by comparison and analysis, that
midazolam might be effective for use for anxiety control during third molar
extraction and can be safely administered by a dedicated staff member. It can
also be used with other drugs to obtain better sedative effects, but the
patient's respiratory function must be monitored closely, because multidrug
sedation is also more risky.
PMID- 25849861
TI - Methadone for Pain: What to Do When the Oral Route Is Not Available.
PMID- 25849863
TI - Correction: High rates of o'nyong nyong and Chikungunya virus transmission in
coastal Kenya.
PMID- 25849862
TI - Mitogen-activated protein kinases are associated with the regulation of
physiological traits and virulence in Fusarium oxysporum f. sp. cubense.
AB - Fusarium oxysporum f. sp. cubense (FOC) is an important soil-borne fungal
pathogen causing devastating vascular wilt disease of banana plants and has
become a great concern threatening banana production worldwide. However, little
information is known about the molecular mechanisms that govern the expression of
virulence determinants of this important fungal pathogen. In this study, we
showed that null mutation of three mitogen-activated protein (MAP) kinase genes,
designated as FoSlt2, FoMkk2 and FoBck1, respectively, led to substantial
attenuation in fungal virulence on banana plants. Transcriptional analysis
revealed that the MAP kinase signaling pathway plays a key role in regulation of
the genes encoding production of chitin, peroxidase, beauvericin and fusaric
acid. Biochemical analysis further confirmed the essential role of MAP kinases in
modulating the production of fusaric acid, which was a crucial phytotoxin in
accelerating development of Fusarium wilt symptoms in banana plants.
Additionally, we found that the MAP kinase FoSlt2 was required for siderophore
biosynthesis under iron-depletion conditions. Moreover, disruption of the MAP
kinase genes resulted in abnormal hypha and increased sensitivity to Congo Red,
Calcofluor White and H2O2. Taken together, these results depict the critical
roles of MAP kinases in regulation of FOC physiology and virulence.
PMID- 25849864
TI - Significance of microbial asynchronous anabolism to soil carbon dynamics driven
by litter inputs.
AB - Soil organic carbon (SOC) plays an important role in the global carbon cycle.
However, it remains largely unknown how plant litter inputs impact magnitude,
composition and source configuration of the SOC stocks over long term through
microbial catabolism and anabolism, mostly due to uncoupled research on litter
decomposition and SOC formation. This limits our ability to predict soil system
responses to changes in land-use and climate. Here, we examine how microbes act
as a valve controlling carbon sequestrated from plant litters versus released to
the atmosphere in natural ecosystems amended with plant litters varying in
quantity and quality. We find that litter quality - not quantity - regulates long
term SOC dynamics under different plausible scenarios. Long-term changes in bulk
SOC stock occur only when the quality of carbon inputs causes asynchronous change
in a microbial physiological trait, defined as "microbial biosynthesis
acceleration" (MBA). This is the first theoretical demonstration that the
response of the SOC stocks to litter inputs is critically determined by the
microbial physiology. Our work suggests that total SOC at an equilibrium state
may be an intrinsic property of a given ecosystem, which ultimately is controlled
by the asynchronous MBA between microbial functional groups.
PMID- 25849865
TI - Actin remodelling factors control ciliogenesis by regulating YAP/TAZ activity and
vesicle trafficking.
AB - Primary cilia exert a profound impact on cell signalling and cell cycle
progression. Recently, actin cytoskeleton destabilization has been recognized as
a dominant inducer of ciliogenesis, but the exact mechanisms regulating
ciliogenesis remain poorly understood. Here we show that the actin cytoskeleton
remodelling controls ciliogenesis by regulating transcriptional coactivator
YAP/TAZ as well as ciliary vesicle trafficking. Cytoplasmic retention of YAP/TAZ
correlates with active ciliogenesis either in spatially confined cells or in
cells treated with an actin filament destabilizer. Moreover, knockdown of YAP/TAZ
is sufficient to induce ciliogenesis, whereas YAP/TAZ hyperactivation suppresses
serum starvation-mediated ciliogenesis. We also identify actin remodelling
factors LIMK2 and TESK1 as key players in the ciliogenesis control network in
which YAP/TAZ and directional vesicle trafficking are integral components. Our
work provides new insights for understanding the link between actin dynamics and
ciliogenesis.
PMID- 25849866
TI - Low-temperature growth of bismuth thin films with (111) facet on highly oriented
pyrolytic graphite.
AB - The epitaxial growth of artificial two-dimensional metals at interfaces plays a
key role in fabricating heterostructures for nanoelectronics. Here, we present
the growth of bismuth nanostructures on highly oriented pyrolytic graphite (HOPG)
under ultrahigh vacuum (UHV) conditions, which was investigated thoroughly by a
combination of scanning tunneling microscopy (STM), ultraviolet photoemission
spectroscopy (UPS), X-ray photoelectron spectroscopy (XPS), and low energy
electron diffraction (LEED). It was found that (111)-oriented bilayers are formed
on as-cleaved high-quality HOPG at 140 K, which opens the possibility of making
Bi(111) thin films on a semimetal, and this is a notable step forward from the
earlier studies, which show that only Bi(110) facets could be formed at ultrathin
thickness at room temperature. XPS investigation of both C 1s and Bi 4f reflects
the rather weak bonding between the Bi film and the HOPG substrate and suggests a
quasi layer-by-layer growth mode of Bi nanostructures on HOPG at low temperature.
Moreover, the evolution of the valence band of the interface is recorded by UPS,
and a transition from quantum well states to bulk-like features is observed at
varying film thickness. Unlike semimetallic bulk bismuth, ultrathin Bi(111) films
are expected to be topological insulators. Our study may therefore pave the way
for the generation of high quality Bi nanostructures to be used in spin
electronics.
PMID- 25849868
TI - A phosphatidylinositol-4-phosphate powered exchange mechanism to create a lipid
gradient between membranes.
AB - Lipids are unevenly distributed within eukaryotic cells, thus defining organelle
identity. How non-vesicular transport mechanisms generate these lipid gradients
between membranes remains a central question. Here using quantitative, real-time
lipid transport assays, we demonstrate that Osh4p, a sterol/phosphatidylinositol
4-phosphate (PI(4)P) exchanger of the ORP/Osh family, transports sterol against
its gradient between two membranes by dissipating the energy of a PI(4)P
gradient. Sterol transport is sustained through the maintenance of this PI(4)P
gradient by the PI(4)P-phosphatase Sac1p. Differences in lipid packing between
membranes can stabilize sterol gradients generated by Osh4p and modulate its
lipid exchange capacity. The ability of Osh4p to recognize sterol and PI(4)P via
distinct modalities and the dynamics of its N-terminal lid govern its activity.
We thus demonstrate that an intracellular lipid transfer protein actively
functions to create a lipid gradient between membranes.
PMID- 25849867
TI - Oxidation by neutrophils-derived HOCl increases immunogenicity of proteins by
converting them into ligands of several endocytic receptors involved in antigen
uptake by dendritic cells and macrophages.
AB - The initiation of adaptive immune responses to protein antigens has to be
preceded by their uptake by antigen presenting cells and intracellular
proteolytic processing. Paradoxically, endocytic receptors involved in antigen
uptake do not bind the majority of proteins, which may be the main reason why
purified proteins stimulate at most weak immune responses. A shared feature of
different types of adjuvants, capable of boosting immunogenicity of protein
vaccines, is their ability to induce acute inflammation, characterized by early
influx of activated neutrophils. Neutrophils are also rapidly recruited to sites
of tissue injury or infection. These cells are the source of potent oxidants,
including hypochlorous acid (HOCl), causing oxidation of proteins present in
inflammatory foci. We demonstrate that oxidation of proteins by endogenous,
neutrophils-derived HOCl increases their immunogenicity. Upon oxidation,
different, randomly chosen simple proteins (yeast alcohol dehydrogenase, human
and bovine serum albumin) and glycoproteins (human apo-transferrin, ovalbumin)
gain the ability to bind with high affinity to several endocytic receptors on
antigen presenting cells, which seems to be the major mechanism of their
increased immunogenicity. The mannose receptor (CD206), scavenger receptors A
(CD204) and CD36 were responsible for the uptake and presentation of HOCl
modified proteins by murine dendritic cells and macrophages. Other scavenger
receptors, SREC-I and LOX-1, as well as RAGE were also able to bind HOCl-modified
proteins, but they did not contribute significantly to these ligands uptake by
dendritic cells because they were either not expressed or exhibited preference
for more heavily oxidised proteins. Our results indicate that oxidation by
neutrophils-derived HOCl may be a physiological mechanism of conferring
immunogenicity on proteins which in their native forms do not bind to endocytic
receptors. This mechanism might enable the immune system to detect infections
caused by pathogens not recognized by pattern recognition receptors.
PMID- 25849869
TI - Altered Clathrin-Independent Endocytosis in Type A Niemann-Pick Disease Cells and
Rescue by ICAM-1-Targeted Enzyme Delivery.
AB - Pharmaceutical intervention often requires therapeutics and/or their carriers to
enter cells via endocytosis. Therefore, endocytic aberrancies resulting from
disease represent a key, yet often overlooked, parameter in designing therapeutic
strategies. In the case of lysosomal storage diseases (LSDs), characterized by
lysosomal accumulation of undegraded substances, common clinical interventions
rely on endocytosis of recombinant enzymes. However, the lysosomal defect in
these diseases can affect endocytosis, as we recently demonstrated for clathrin
mediated uptake in patient fibroblasts with type A Niemann-Pick disease (NPD), a
disorder characterized by acid sphingomylinase (ASM) deficiency and subsequent
sphingomyelin storage. Using similar cells, we have examined if this is also the
case for clathrin-independent pathways, including caveolae-mediated endocytosis
and macropinocytosis. We observed impaired caveolin-1 enrichment at ligand
binding sites in NPD relative to wild type fibroblasts, corresponding with
altered uptake of ligands and fluid-phase markers by both pathways. Similarly,
aberrant lysosomal storage of sphingomyelin induced by pharmacological means also
diminished uptake. Partial degradation of the lysosomal storage by untargeted
recombinant ASM led to partial uptake enhancement, whereas both parameters were
restored to wild type levels by ASM delivery using model polymer nanocarriers
specifically targeted to intercellular adhesion molecule-1. Carriers also
restored caveolin-1 enrichment at ligand-binding sites and uptake through the
caveolar and macropinocytic routes. These results demonstrate a link between
lysosomal storage in NPD and alterations in clathrin-independent endocytosis,
which could apply to other LSDs. Hence, this study shall guide the design of
therapeutic approaches using viable endocytic pathways.
PMID- 25849870
TI - Perhexiline promotes HER3 ablation through receptor internalization and inhibits
tumor growth.
AB - INTRODUCTION: Human epidermal growth factor receptor HER3 has been implicated in
promoting the aggressiveness and metastatic potential of breast cancer.
Upregulation of HER3 has been found to be a major mechanism underlying drug
resistance to EGFR and HER2 tyrosine kinase inhibitors and to endocrine therapy
in the treatment of breast cancer. Thus, agents that reduce HER3 expression at
the plasma membrane may synergize with current therapies and offer a novel
therapeutic strategy to improve treatment. METHODS: We devised an image-based
screening platform using membrane localized HER3-YFP to identify small molecules
that promote HER3 internalization and degradation. In vitro and in vivo tumor
models were used to characterize the signaling effects of perhexiline, an anti
anginal drug, identified by the screening platform. RESULTS: We found
perhexiline, an anti-anginal drug, selectively internalized HER3, decreased HER3
expression, and subsequently inhibited signaling downstream of HER3. Consistent
with these results, perhexiline inhibited breast cancer cell proliferation in
vitro and tumor growth in vivo. CONCLUSIONS: This is the first demonstration that
HER3 can be targeted with small molecules by eliminating it from the cell
membrane. The novel approach used here led to the discovery that perhexiline
ablates HER3 expression, and offers an opportunity to identify HER3 ablation
modulators as innovative therapeutics to improve survival in breast cancer
patients.
PMID- 25849871
TI - Principles and limitations of stable isotopes in differentiating organic and
conventional foodstuffs: 2. Animal products.
AB - In this review, we examine the variation in stable isotope signatures of the
lighter elements (delta2H, delta13C, delta15N, delta18O, and delta34S) of tissues
and excreta of domesticated animals, the factors affecting the isotopic
composition of animal tissues, and whether stable isotopes may be used to
differentiate organic and conventional modes of animal husbandry. The main
factors affecting the delta13C signatures of livestock are the C3/C4 composition
of the diet, the relative digestibility of the diet components, metabolic
turnover, tissue and compound specificity, growth rate, and animal age. delta15N
signatures of sheep and cattle products have been related mainly to diet
signatures, which are quite variable among farms and between years. Although few
data exist, a minor influence in delta15N signatures of animal products was
attributed to N losses at the farm level, whereas stocking rate showed divergent
findings. Correlations between mode of production and delta2H and delta18O have
not been established, and only in one case of an animal product was delta34S a
satisfactory marker for mode of production. While many data exist on diet-tissue
isotopic discrimination values among domesticated animals, there is a paucity of
data that allow a direct and statistically verifiable comparison of the
differences in the isotopic signatures of organically and conventionally grown
animal products. The few comparisons are confined to beef, milk, and egg yolk,
with no data for swine or lamb products. delta13C appears to be the most
promising isotopic marker to differentiate organic and conventional production
systems when maize (C4) is present in the conventional animal diet. However,
delta13C may be unsuitable under tropical conditions, where C4 grasses are
abundant, and where grass-based husbandry is predominant in both conventional and
organic systems. Presently, there is no universal analytical method that can be
applied to differentiate organic and conventional animal products.
PMID- 25849872
TI - Catalytic chemical amide synthesis at room temperature: one more step toward
peptide synthesis.
AB - An efficient method has been developed for direct amide bond synthesis between
carboxylic acids and amines via (2-(thiophen-2-ylmethyl)phenyl)boronic acid as a
highly active bench-stable catalyst. This catalyst was found to be very effective
at room temperature for a large range of substrates with slightly higher
temperatures required for challenging ones. This methodology can be applied to
aliphatic, alpha-hydroxyl, aromatic, and heteroaromatic acids as well as primary,
secondary, heterocyclic, and even functionalized amines. Notably, N-Boc-protected
amino acids were successfully coupled in good yields with very little
racemization. An example of catalytic dipeptide synthesis is reported.
PMID- 25849874
TI - Collaboration in the new millennium.
AB - The presidential addresses of the Society for Psychotherapy Research (SPR) of the
past decade convey a consistency of format and themes. They highlight significant
weaknesses in some of the basic questions and methodologies of psychotherapy
researchers. These include neglect of topics concerning the understanding of
change and over-valuation of the randomized clinical trial (RCT). Although valid,
the criticisms neglect the strengths of RCTs, which are illustrated by a series
of psychotherapy clinical trials conducted by the author's research team, and run
the risk of polarizing psychotherapy researchers. The new millennium is an
appropriate time to acknowledge how different methodologies complement each other
and advance knowledge in ways that could not occur in the absence of others. SPR
is an international, multidisciplinary scientific organization that emphasizes
inclusiveness. Nevertheless, it, as well as other organizations, can further
enhance its contribution to the field by extending its range of collaboration to
include underrepresented researchers, disciplines, and research-oriented
clinicians.
PMID- 25849873
TI - The relationship between regular sports participation and vigilance in male and
female adolescents.
AB - The present study investigated the relationship between regular sport
participation (soccer) and vigilance performance. Two groups of male and female
adolescents differentiated in terms of their sport participation (athletes, n =
39, and non-athletes, n = 36) took part in the study. In one session,
participants performed the Leger Multi-stage fitness test to estimate their
aerobic fitness level. In the other session, participants completed the
Psychomotor Vigilance Task (PVT) to evaluate their vigilance performance.
Perceived arousal prior to the task and motivation toward the task were also
measured in the PVT session. The results revealed that athletes had better
cardiovascular fitness and showed better performance in the PVT. However,
correlation analyses did not show any significant relationship between
cardiovascular fitness and performance in the PVT. Athletes showed larger scores
in motivation and perceived arousal measures with respect to non-athletes,
although, once again, these variables were not correlated with PVT performance.
Gender differences were observed only in the Leger test, with males showing
greater fitness level than females. The major outcome of this research points to
a positive relationship between regular sport participation and vigilance during
adolescence. This relationship did not seem to be influenced by gender, perceived
arousal, motivation toward the task or cardiovascular fitness. We discuss our
results in terms of the different hypotheses put forward in the literature to
explain the relationship between physical activity and cognitive functioning.
PMID- 25849875
TI - Investigating follow-up outcome change using hierarchical linear modeling.
AB - Individual change in outcome during a one-year follow-up period for 98 patients
who received either interpretive or supportive psychotherapy was examined using
hierarchical linear modeling (HLM). This followed a previous study that had
investigated average (treatment condition) change during follow-up using
traditional methods of data analysis (repeated measures ANOVA, chi-square tests).
We also investigated whether two patient personality characteristics-quality of
object relations (QOR) and psychological mindedness (PM)-predicted individual
change. HLM procedures yielded findings that were not detected using traditional
methods of data analysis. New findings indicated that the rate of individual
change in outcome during follow-up varied significantly among the patients. QOR
was directly related to favorable individual change for supportive therapy
patients, but not for patients who received interpretive therapy. The findings
have implications for determining which patients will show long-term benefit
following short-term supportive therapy and how to enhance it. The study also
found significant associations between QOR and final outcome level.
PMID- 25849876
TI - Evaluating the phase model of change during short-term psychodynamic
psychotherapy.
AB - This study examined the phase model of psychotherapy change (Howard, Lueger,
Maling, & Martinovich, 1993; Howard, Moras, Brill, Martinovich, & Lutz, 1996) and
assessed the domains of subjective well-being, symptomatic distress, and
social/interpersonal functioning during short-term psychodynamic psychotherapy.
Specifically, we assessed evaluation/third-session to ninth-session changes in a
group of 20 treated patients. These three domains were examined for both
statistical and clinically significant change (Jacobson & Truax, 1991). Treatment
fidelity and credibility were also evaluated. Statistical and clinically
significant improvement in the domains of subjective well-being and symptom
distress were evident by the ninth session of short-term dynamic psychotherapy.
Statistical and reliable improvement were observed in relational functioning
during the same time period. In addition, changes in both subjective well-being
and symptomatic distress contributed unique and separate variance to predicting
changes in social/interpersonal functioning. The results with respect to the
differential effects predicted by the phase model of change during the early
course of treatment are discussed.
PMID- 25849877
TI - The effects of providing therapists with feedback on patient progress during
psychotherapy: are outcomes enhanced?
AB - Patient-focused research attempts to provide information that answers the
question: Is this treatment benefiting this patient? Although several systems
have been developed to monitor and provide feedback about a patient's response to
psychotherapy, few if any have been tested empirically. The current study divided
609 patients into four groups (two experimental and two control) to determine if
feedback regarding patient progress, when provided to a therapist, affected
patient outcome and number of sessions attended. Results showed that feedback
increased the duration of treatment and improved outcome relative to patients in
the control condition who were predicted to be treatment failures. Twice as many
patients in the feedback group achieved clinically significant or reliable change
and one-third as many were classified as deteriorated by the time treatment
ended. For those patients who were predicted to have a positive response to
treatment, feedback to therapists resulted in a reduction in the number of
treatment sessions without reducing positive outcomes.
PMID- 25849878
TI - Psychometric Properties of the Psychotherapy Expectancy Inventory-Revised (PEI
R).
AB - The Psychotherapy Expectancy Inventory-Revised (PEI-R) was developed to measure
clients' expectations of behavior in counseling. An exploratory factor analysis
of the original PEI-R (Rickers-Ovsiankina, Berzins, Geller, & Rogers, 1971) on a
sample of clients yielded four factors: approval, advice, audience and
relationship (Berzins, 1971). The aim of the study presented in this paper is to
examine the internal construct validity of the PEI-R by means of a confirmatory
factor analysis on data gathered in a sample of 159 clients. The analysis
revealed an adequate model fit for the four-dimensional oblique model. However,
detailed inspection of model fit suggest the possibility of a fifth factor. Data
concerning the reliability and the relationship with demographics are also
provided.
PMID- 25849879
TI - Schemas, affect consciousness, and cluster C personality pathology: a prospective
one-year follow-up study of patients in a schema-focused short-term treatment
program.
AB - In this prospective study the aim was to investigate the relationship between
affect consciousness and Cluster C personality pathology (DSM-IV, Axis-II). Forty
four patients with panic disorder and/or agoraphobia and Cluster C personality
traits were treated in a schema-focused program comprising a first
panic/agoraphobia-focused phase and a second personality-focused phase, being
finally assessed at a one-year follow-up. According to the treatment strategy,
affect consciousness was expected to change during the second phase, independent
of change in agoraphobic avoidance being focused in the first phase. Pretreatment
level of affect consciousness during treatment was related to a reduction in
avoidant personality pathology (not dependent or obsessive-compulsive) from
pretreatment to follow-up, while increase in affect consciousness did not
contribute in the same way. These results indicate that affect consciousness is
important as a selection criterion, as a parameter in treatment with focus on
schemas and schema-avoidance, and as a predictor for outcome in agoraphobic
patients with avoidant personality pathology.
PMID- 25849880
TI - Affective indicators of the psychotherapeutic process: an empirical case study.
AB - By analyzing facial expressions of emotion and the emotional experience of a
patient and a psychotherapist, we attempted to objectively register unconscious
interaction processes that could have contributed to the failure of a
psychotherapy that ended prematurely. In this connection, the affect 'contempt'
played a particular role. It is made clear how an unconscious enactment results
in a gap between emotional expression and experience. In addition, the
countertransference of the psychotherapist is examined and the emotional
experience is contrasted with her affective behavior. In this study, it is
demonstrated how this particular psychotherapy failed due to a lack of
acknowledging the involvement of the interactive dynamics.
PMID- 25849881
TI - Helping the Hard-Core Smoker: A Clinician's Guide.
PMID- 25849882
TI - Socioeconomic position, health behaviors, and racial disparities in cause
specific infant mortality in Michigan, USA.
AB - OBJECTIVES: Studies about racial disparities in infant mortality suggest that
racial differences in socioeconomic position (SEP) and maternal risk behaviors
explain some, but not all, excess infant mortality among Blacks relative to non
Hispanic Whites. We examined the contribution of these to disparities in specific
causes of infant mortality. METHODS: We analyzed data about 2,087,191 mother
child dyads in Michigan between 1989 and 2005. First, we calculated crude Black
White infant mortality ratios independently and by specific cause of death.
Second, we fit multivariable Poisson regression models of infant mortality,
overall and by cause, adjusting for SEP and maternal risk behaviors. Third, Crude
Black-White mortality ratios were compared to adjusted predicted probability
ratios, overall and by specific cause. RESULTS: SEP and maternal risk behaviors
explained nearly a third of the disparity in infant mortality overall, and over
25% of disparities in several specific causes including homicide, accident,
sudden infant death syndrome, and respiratory distress syndrome. However, SEP and
maternal risk behaviors had little influence on disparities in other specific
causes, such as septicemia and congenital anomalies. CONCLUSIONS: These findings
help focus policy attention toward disparities in those specific causes of infant
mortality most amenable to social and behavioral intervention, as well as
research attention to disparities in specific causes unexplained by SEP and
behavioral differences.
PMID- 25849884
TI - Correction: PDCD10 gene mutations in multiple cerebral cavernous malformations.
PMID- 25849883
TI - Disparities in long-term cardiovascular disease risk by sexual identity: The
National Longitudinal Study of Adolescent to Adult Health.
AB - OBJECTIVE: To examine long-term cardiovascular disease (CVD) risk disparities by
sexual identity using a nationally representative sample of young adults in the
United States. METHODS: Data include participants in wave 4 (2008/09; ages 24
34years) of the National Longitudinal Study of Adolescent to Adult Health (7087
females; 6340 males). Sexual identity was self-reported (heterosexual, mostly
heterosexual, bisexual, mostly homosexual, homosexual) and a Framingham-based
prediction model was used to estimate participants' risk of a CVD event over
30years. Differences in CVD risk by sexual identity, relative to heterosexuals,
were calculated with linear regression models adjusted for age, race/ethnicity,
education, and financial distress. RESULTS: Average 30-year CVD risk was 17.2%
(95% CI: 16.7, 17.7) in males and 9.0% (95% CI: 8.6, 9.3) in females. Compared to
heterosexual females, mostly heterosexual (0.8%; 95% CI: 0.2, 1.4) and mostly
homosexual females (2.8%; 95% CI: 0.8, 4.9) had higher CVD risk. Bisexual and
homosexual females had higher but not statistically significant CVD risk compared
to heterosexuals. Among males, differences in CVD risk by sexual identity were
not statistically significant. CONCLUSION: Sexual identity was associated with
CVD risk in sexual minority subgroups. Population- and clinic-based prevention
strategies are needed to minimize disparities in subsequent disease.
PMID- 25849885
TI - Low pH increases the yield of exosome isolation.
AB - Exosomes are the extracellular vesicles secreted by various cells. Exosomes
mediate intercellular communication by delivering a variety of molecules between
cells. Cancer cell derived exosomes seem to be related with tumor progression and
metastasis. Tumor microenvironment is thought to be acidic and this low pH
controls exosome physiology, leading to tumor progression. Despite the importance
of microenvironmental pH on exosome, most of exosome studies have been performed
without regard to pH. Therefore, the difference of exosome stability and yield of
isolation by different pH need to be studied. In this research, we investigated
the yield of total exosomal protein and RNA after incubation in acidic, neutral
and alkaline conditioned medium. Representative exosome markers were investigated
by western blot after incubation of exosomes in different pH. As a result, the
concentrations of exosomal protein and nucleic acid were significantly increased
after incubation in the acidic medium compared with neutral medium. The higher
levels of exosome markers including CD9, CD63 and HSP70 were observed after
incubation in an acidic environment. On the other hand, no exosomal protein,
exosomal RNA and exosome markers have been detected after incubation in an
alkaline condition. In summary, our results indicate that the acidic condition is
the favorable environment for existence and isolation of exosomes.
PMID- 25849886
TI - Effect of TGFbeta on calcium signaling in megakaryocytes.
AB - TGFbeta is a powerful regulator of megakaryocyte maturation and platelet
formation. As previously shown for other cell types, TGFbeta may up-regulate the
expression of the serum & glucocorticoid inducible kinase SGK1, an effect
requiring p38 kinase. SGK1 has in turn recently been shown to participate in the
regulation of cytosolic Ca(2+) activity ([Ca(2+)]i) in megakaryocytes and
platelets. SGK1 phosphorylates the IkappaB kinase (IKKalpha/beta), which in turn
phosphorylates the inhibitor protein IkappaBalpha resulting in nuclear
translocation of nuclear factor NFkappaB. Genes up-regulated by NFkappaB include
Orai1, the pore forming ion channel subunit accomplishing store operated Ca(2+)
entry (SOCE). The present study explored whether TGFbeta influences Ca(2+)
signaling in megakaryocytes. [Ca(2+)]i was determined by Fura-2 fluorescence and
SOCE from the increase of [Ca(2+)]i following re-addition of extracellular Ca(2+)
after store depletion by removal of extracellular Ca(2+) and inhibition of the
sarcoendoplasmatic Ca(2+) ATPase (SERCA) with thapsigargin (1 MUM). As a result,
TGFbeta (60 ng, 24 h) increased SOCE, an effect significantly blunted by p38
kinase inhibitor Skepinone-L (1 MUM), SGK1 inhibitor EMD638683 (50 MUM) and
NFkappaB inhibitor wogonin (100 MUM). In conclusion, TGFbeta is a powerful
regulator of store operated Ca(2+) entry into megakaryocytes, an effect mediated
by a signaling cascade involving p38 kinase, SGK1 and NFkappaB.
PMID- 25849887
TI - Crystal structures of YfiR from Pseudomonas aeruginosa in two redox states.
AB - YfiBNR is a recently identified c-di-GMP regulatory system involved in bacterial
biofilm formation. The periplasmic protein YfiR inhibits the diguanylate cyclase
activity of the inner membrane protein YfiN, whereas YfiB in the outer membrane
can release this inhibition by sequestration of YfiR. In addition, this system
may respond to anoxic conditions via YfiR, although the detailed mechanism is
still unknown. Here we report crystal structures of Pseudomonas aeruginosa YfiR
in the absence and presence of oxidative glutathione. Our structures reveal the
overall folding of YfiR for the first time and demonstrate that YfiR exist as a
dimer. Comparison of the two structures in different redox states revealed a
broken/formation of one disulfide bond (Cys71-Cys110) and local conformational
change around the other one (Cys145-Cys152). Mutagenesis studies indicated that
Cys145-Cys152 plays an important role in maintaining the correct folding of YfiR.
PMID- 25849888
TI - beta-Catenin expression is regulated by an IRES-dependent mechanism and
stimulated by paclitaxel in human ovarian cancer cells.
AB - Paclitaxel (PTX) is commonly used in the chemotherapy of ovarian cancer, but
resistance occurs in most cases, allowing cancer progression. The Wnt/beta
catenin pathway has been associated with this resistance, but there are no
reports on the regulation of beta-catenin expression at the translational level.
In the present study, we found that PTX induced different transcription and
translation levels of beta-catenin in the human ovarian cancer cell lines A2780
and SKOV3. We also demonstrated that beta-catenin mRNA contained an internal
ribosome entry segment (IRES) that regulated its translation. Using gene
transfection and reporter assays, we revealed that the entire CTNNB1 5'
untranslated region (UTR) contributed to IRES activity. Interestingly, we found
that c-myc and cyclin D1 increased significantly in transfected cells with
increasing PTX concentration, and cell-survival rates remained at 60% while the
PTX concentration increased. Suppressing beta-catenin resulted in decreased
expression of c-myc and cyclin D1 and made these cells less resistant. These
results indicate that beta-catenin translation is initiated via the IRES and this
is regulated by PTX, suggesting that regulation of the IRES-dependent translation
of beta-catenin may be involved in the cancer cell response to PTX treatment.
PMID- 25849890
TI - Green tea catechins enhance norepinephrine-induced lipolysis via a protein kinase
A-dependent pathway in adipocytes.
AB - Green tea catechins have been shown to attenuate obesity in animals and humans.
The catechins activate adenosine monophosphate-activated protein kinase (AMPK),
and thereby increase fatty acid oxidation in liver and skeletal muscles. Green
tea catechins have also been shown to reduce body fat in humans. However, the
effect of the catechins on lipolysis in adipose tissue has not been fully
understood. The aim of this study was to clarify the effect of green tea
catechins on lipolysis in adipocytes and to elucidate the underlying mechanism.
Differentiated mouse adipocyte cell line (3T3-L1) was stimulated with green tea
catechins in the presence or absence of norepinephrine. Glycerol and free fatty
acids in the media were measured. Phosphorylation of hormone-sensitive lipase
(HSL) was determined by Western blotting, and the mRNA expression levels of HSL,
adipose triglyceride lipase (ATGL), and perilipin were determined by quantitative
RT-PCR. The cells were treated with inhibitors of protein kinase A (PKA), protein
kinase C (PKC), protein kinase G (PKG), or mitogen-activated protein kinase
(MAPK) to determine the responsible pathway. Treatment of 3T3-L1 adipocytes with
green tea catechins increased the level of glycerol and free fatty acids released
into the media in the presence, but not absence, of norepinephrine, and increased
the level of phosphorylated HSL in the cells. The catechins also increased mRNA
and protein levels of HSL and ATGL. PKA inhibitor (H89) attenuated the catechin
induced increase in glycerol release and HSL phosphorylation. The results
demonstrate that green tea catechins enhance lipolysis in the presence of
norepinephrine via a PKA-dependent pathway in 3T3-L1 adipocytes, providing a
potential mechanism by which green tea catechins could reduce body fat.
PMID- 25849889
TI - Role of methylthioadenosine/S-adenosylhomocysteine nucleosidase in Vibrio
cholerae cellular communication and biofilm development.
AB - In Vibrio cholerae, the genes required for biofilm development are repressed by
quorum sensing at high cell density due to the accumulation in the medium of two
signaling molecules, cholera autoinducer 1 (CAI-1) and autoinducer 2 (AI-2). A
significant fraction of toxigenic V. cholerae isolates, however, exhibit
dysfunctional quorum sensing pathways. It was reported that transition state
analogs of the enzyme methylthioadenosine/S-adenosylhomocysteine nucleosidase
(MtnN) required to make AI-2 inhibited biofilm formation in the prototype quorum
sensing-deficient strain N16961. This finding prompted us to examine the role of
both autoinducers and MtnN in biofilm development and virulence gene expression
in a quorum sensing-deficient genetic background. Here we show that deletion of
mtnN encoding methylthioadenosine/S-adenosylhomocysteine nucleosidase, cqsA (CAI
1), and/or luxS (AI-2) do not prevent biofilm development. However, two
independent mtnN mutants exhibited diminished growth rate and motility in swarm
agar plates suggesting that, under certain conditions, MtnN could influence
biofilm formation indirectly. Nevertheless, MtnN is not required for the
development of a mature biofilm.
PMID- 25849891
TI - Involvement of the orexin system in sympathetic nerve regulation.
AB - Orexin, also known as hypocretin, is a secreted neuropeptide implicated in the
regulation of sleep and food intake. In the present study, we examined the
importance of orexin in regulation of the sympathetic nervous system using an
orexin/ataxin-3 transgenic (OXTg) rat, which has a minimal number of orexin
neurons. RT-PCR analysis identified expression of prepro-orexin and orexin
receptor-1 (OX1R) in the superior cervical ganglion (SCG), and expression of
another receptor (OX2R) was marginal in the wild-type rat. The orexin/ataxin-3
transgenic rat showed increased expression of OX1R and OX2R, whereas expression
of prepro-orexin was undetectable, suggesting a compensatory increase in both
receptors. In the ECG recording (R-R interval), orexin/ataxin-3 transgenic rats
showed decreased responsiveness to the beta-adrenergic blocker propranolol.
Furthermore, OXTg rats had deteriorated R-R interval regulation, indicating
involvement of the orexin system in sympathetic nerve regulation. This was
accompanied by decreased baroreflex and responsiveness to beta-adrenergic blocker
in blood pressure recording, also suggesting involvement of the orexin system in
sympathetic nerve regulation. Histological examination revealed hypotrophic
changes in the transgenic heart, suggesting involvement of the orexin system in
cardiac development. Taken together, our present results indicate involvement of
the orexin system in sympathetic nerve control.
PMID- 25849892
TI - Diverse effects of LPA4, LPA5 and LPA6 on the activation of tumor progression in
pancreatic cancer cells.
AB - Lysophosphatidic acid (LPA) is an extracellular biological lipid which interacts
with G protein-coupled LPA receptors (LPA1 to LPA6). LPA signaling via LPA
receptors mediates several cellular responses. In the present study, to assess
the roles of LPA4, LPA5 and LPA6 in cellular functions of pancreatic cancer
cells, we generated LPA receptor knockdown cells from PANC-1 cells (PANC-sh4,
PANC-sh5 and PANC-sh6 cells, respectively). In cell motility assay, PANC-sh4 and
PANC-sh5 cells enhanced the cell motile activities, compared with control cells.
In contrast, the cell motile activity of PANC-sh6 cells was suppressed. The
invasive activities of PANC-sh4 and PANC-sh5 cells were markedly stimulated,
while PANC-sh6 cells showed the low invasive activity. In colony assay, PANC-sh4
and PANC-sh5 cells formed the large sized colonies, but not PANC-sh6 cells. When
endothelial cells were incubated with supernatants from PANC-sh4 and PANC-sh5
cells, the cell motility and tube formation of endothelial cells were
significantly induced, but not PANC-sh6 cells. These results suggest that the
diverse roles of LPA4, LPA5 and LPA6 are involved in the activation of tumor
progression in pancreatic cancer cells.
PMID- 25849893
TI - TYK2 protein-coding variants protect against rheumatoid arthritis and
autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune
complex traits.
AB - Despite the success of genome-wide association studies (GWAS) in detecting a
large number of loci for complex phenotypes such as rheumatoid arthritis (RA)
susceptibility, the lack of information on the causal genes leaves important
challenges to interpret GWAS results in the context of the disease biology. Here,
we genetically fine-map the RA risk locus at 19p13 to define causal variants, and
explore the pleiotropic effects of these same variants in other complex traits.
First, we combined Immunochip dense genotyping (n = 23,092 case/control samples),
Exomechip genotyping (n = 18,409 case/control samples) and targeted exon
sequencing (n = 2,236 case/controls samples) to demonstrate that three protein
coding variants in TYK2 (tyrosine kinase 2) independently protect against RA:
P1104A (rs34536443, OR = 0.66, P = 2.3 x 10(-21)), A928V (rs35018800, OR = 0.53,
P = 1.2 x 10(-9)), and I684S (rs12720356, OR = 0.86, P = 4.6 x 10(-7)). Second,
we show that the same three TYK2 variants protect against systemic lupus
erythematosus (SLE, Pomnibus = 6 x 10(-18)), and provide suggestive evidence that
two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory
bowel disease (IBD; P(omnibus) = 0.005). Finally, in a phenome-wide association
study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR)
in >29,000 subjects, we found no convincing evidence for association of P1104A
and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE
and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis
of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug
target for the treatment of autoimmune diseases.
PMID- 25849894
TI - Human Parvovirus B19 and blood product safety: a tale of twenty years of
improvements.
PMID- 25849895
TI - Spectroscopic studies reveal that the heme regulatory motifs of heme oxygenase-2
are dynamically disordered and exhibit redox-dependent interaction with heme.
AB - Heme oxygenase (HO) catalyzes a key step in heme homeostasis: the O2- and NADPH
cytochrome P450 reductase-dependent conversion of heme to biliverdin, Fe, and CO
through a process in which the heme participates both as a prosthetic group and
as a substrate. Mammals contain two isoforms of this enzyme, HO2 and HO1, which
share the same alpha-helical fold forming the catalytic core and heme binding
site, as well as a membrane spanning helix at their C-termini. However, unlike
HO1, HO2 has an additional 30-residue N-terminus as well as two cysteine-proline
sequences near the C-terminus that reside in heme regulatory motifs (HRMs). While
the role of the additional N-terminal residues of HO2 is not yet understood, the
HRMs have been proposed to reversibly form a thiol/disulfide redox switch that
modulates the affinity of HO2 for ferric heme as a function of cellular redox
poise. To further define the roles of the N- and C-terminal regions unique to
HO2, we used multiple spectroscopic techniques to characterize these regions of
the human HO2. Nuclear magnetic resonance spectroscopic experiments with HO2
demonstrate that, when the HRMs are in the oxidized state (HO2(O)), both the
extra N-terminal and the C-terminal HRM-containing regions are disordered.
However, protein NMR experiments illustrate that, under reducing conditions, the
C-terminal region gains some structure as the Cys residues in the HRMs undergo
reduction (HO2(R)) and, in experiments employing a diamagnetic protoporphyrin,
suggest a redox-dependent interaction between the core and the HRM domains.
Further, electron nuclear double resonance and X-ray absorption spectroscopic
studies demonstrate that, upon reduction of the HRMs to the sulfhydryl form, a
cysteine residue from the HRM region ligates to a ferric heme. Taken together
with EPR measurements, which show the appearance of a new low-spin heme signal in
reduced HO2, it appears that a cysteine residue(s) in the HRMs directly interacts
with a second bound heme.
PMID- 25849897
TI - Monaural Auditory Cue Affects the Process of Choosing the Initial Swing Leg in
Gait Initiation.
AB - The authors investigated the effect of an auditory cue on the choice of the
initial swing leg in gait initiation. Healthy humans initiated a gait in response
to a monaural or binaural auditory cue. When the auditory cue was given in the
ear ipsilateral to the preferred leg side, the participants consistently
initiated their gait with the preferred leg. In the session in which the side of
the monaural auditory cue was altered trial by trial randomly, the probability of
initiating the gait with the nonpreferred leg increased when the auditory cue was
given in the ear contralateral to the preferred leg side. The probability of
choosing the nonpreferred leg did not increase significantly when the auditory
cue was given in the ear contralateral to the preferred leg side in the session
in which the auditory cue was constantly given in the ear contralateral to the
preferred leg side. The reaction time of anticipatory postural adjustment was
shortened, but the probability of choosing the nonpreferred leg was not
significantly increased when the gait was initiated in response to a binaural
auditory cue. An auditory cue in the ear contralateral to the preferred leg side
weakens the preference for choosing the preferred leg as the initial swing leg in
gait initiation when the side of the auditory cue is unpredictable.
PMID- 25849896
TI - Impacts of nucleotide fixation during soybean domestication and improvement.
AB - BACKGROUND: Plant domestication involves complex morphological and physiological
modification of wild species to meet human needs. Artificial selection during
soybean domestication and improvement results in substantial phenotypic
divergence between wild and cultivated soybeans. Strong selective pressure on
beneficial phenotypes could cause nucleotide fixations in the founder population
of soybean cultivars in quite a short time. RESULTS: Analysis of available
sequencing accessions estimates that ~5.3 million single nucleotide variations
reach saturation in cultivars, and then ~9.8 million in soybean germplasm.
Selective sweeps defined by loss of genetic diversity reveal 2,255 and 1,051
genes were involved in domestication and subsequent improvement, respectively.
Both processes introduced ~0.1 million nucleotide fixations, which contributed to
the divergence of wild and cultivated soybeans. Meta-analysis of reported
quantitative trait loci (QTL) and selective signals with nucleotide fixation
identifies a series of putative candidate genes responsible for 13 agronomically
important traits. Nucleotide fixation mediated by artificial selection affected
diverse molecular functions and biological reactions that associated with soybean
morphological and physiological changes. Of them, plant-pathogen interactions are
of particular relevance as selective nucleotide fixations happened in disease
resistance genes, cyclic nucleotide-gated ion channels and terpene synthases.
CONCLUSIONS: Our analysis provides insights into the impacts of nucleotide
fixation during soybean domestication and improvement, which would facilitate
future QTL mapping and molecular breeding practice.
PMID- 25849898
TI - Human factors/ergonomics implications of big data analytics: Chartered Institute
of Ergonomics and Human Factors annual lecture.
AB - In recent years, advances in sensor technology, connectedness and computational
power have come together to produce huge data-sets. The treatment and analysis of
these data-sets is known as big data analytics (BDA), and the somewhat related
term data mining. Fields allied to human factors/ergonomics (HFE), e.g.
statistics, have developed computational methods to derive meaningful, actionable
conclusions from these data bases. This paper examines BDA, often characterised
by volume, velocity and variety, giving examples of successful BDA use. This
examination provides context by considering examples of using BDA on human data,
using BDA in HFE studies, and studies of how people perform BDA. Significant
issues for HFE are the reliance of BDA on correlation rather than hypotheses and
theory, the ethics of BDA and the use of HFE in data visualisation.
PMID- 25849899
TI - Cell type-specific responses to wingless, hedgehog and decapentaplegic are
essential for patterning early eye-antenna disc in Drosophila.
AB - The Drosophila eye-antenna imaginal disc (ead) is a flattened sac of two-layered
epithelia, from which most head structures are derived. Secreted morphogens like
Wingless (Wg), Hedgehog (Hh), and Decapentaplegic (Dpp) are important for early
patterning of ead, but the underlying mechanisms are still largely unknown. To
understand how these morphogens function in the ead of early larval stages, we
used wg-LacZ and dpp-Gal4 markers for the examination of wild-type and mutant
eads. We found that the ead immediately after hatching was crescent-shaped with
the Bolwig's nerve at the ventral edge, suggesting that it consists of dorsal
domain. In a subsequent step, transcriptional induction of dpp in the cells along
the Bolwig's nerve was followed by rapid growth of the ventral domain. Both Wg
and Hh were required for the formation of the ventral domain. Wg was crucial for
the growth of the entire ead, but Hh was essential for cell division only in the
dorsal domain. In the ventral domain, Hh regulated dpp transcription. Based on
these data, we propose that signaling among distinct groups of cells expressing
Wg, Dpp, or Hh in the ead of the first-instar larvae are critical for coordinated
growth and patterning of ead.
PMID- 25849901
TI - Interferometric nanoporous anodic alumina photonic coatings for optical sensing.
AB - Herein, we present a systematic study on the development, optical optimization
and sensing applicability of colored photonic coatings based on nanoporous anodic
alumina films grown on aluminum substrates. These optical nanostructures, so
called distributed Bragg reflectors (NAA-DBRs), are fabricated by galvanostatic
pulse anodization process, in which the current density is altered in a periodic
manner in order to engineer the effective medium of the resulting photonic
coatings. As-prepared NAA-DBR photonic coatings present brilliant interference
colors on the surface of aluminum, which can be tuned at will within the UV
visible spectrum by means of the anodization profile. A broad library of NAA-DBR
colors is produced by means of different anodization profiles. Then, the
effective medium of these NAA-DBR photonic coatings is systematically assessed in
terms of optical sensitivity, low limit of detection and linearity by
reflectometric interference spectroscopy (RIfS) in order to optimize their
nanoporous structure toward optical sensors with enhanced sensing performance.
Finally, we demonstrate the applicability of these photonic nanostructures as
optical platforms by selectively detecting gold(iii) ions in aqueous solutions.
The obtained results reveal that optimized NAA-DBR photonic coatings can achieve
an outstanding sensing performance for gold(iii) ions, with a sensitivity of
22.16 nm MUM(-1), a low limit of detection of 0.156 MUM (i.e. 30.7 ppb) and
excellent linearity within the working range (0.9983).
PMID- 25849900
TI - Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from
promoters and enhancers.
AB - Technologies that enable targeted manipulation of epigenetic marks could be used
to precisely control cell phenotype or interrogate the relationship between the
epigenome and transcriptional control. Here we describe a programmable, CRISPR
Cas9-based acetyltransferase consisting of the nuclease-null dCas9 protein fused
to the catalytic core of the human acetyltransferase p300. The fusion protein
catalyzes acetylation of histone H3 lysine 27 at its target sites, leading to
robust transcriptional activation of target genes from promoters and both
proximal and distal enhancers. Gene activation by the targeted acetyltransferase
was highly specific across the genome. In contrast to previous dCas9-based
activators, the acetyltransferase activates genes from enhancer regions and with
an individual guide RNA. We also show that the core p300 domain can be fused to
other programmable DNA-binding proteins. These results support targeted
acetylation as a causal mechanism of transactivation and provide a robust tool
for manipulating gene regulation.
PMID- 25849902
TI - Adult active transport in the Netherlands: an analysis of its contribution to
physical activity requirements.
AB - INTRODUCTION: Modern, urban lifestyles have engineered physical activity out of
everyday life and this presents a major threat to human health. The Netherlands
is a world leader in active travel, particularly cycling, but little research has
sought to quantify the cumulative amount of physical activity through everyday
walking and cycling. METHODS: Using data collected as part of the Dutch National
Travel Survey (2010 - 2012), this paper determines the degree to which Dutch
walking and cycling contributes to meeting minimum level of physical activity of
150 minutes of moderate intensity aerobic activity throughout the week. The
sample includes 74,465 individuals who recorded at least some travel on the day
surveyed. As physical activity benefits are cumulative, all walking and cycling
trips are analysed, including those to and from public transport. These trips are
then converted into an established measure of physical activity intensity, known
as metabolic equivalents of tasks. Multivariate Tobit regression models were
performed on a range of socio-demographic, transport resources, urban form and
meteorological characteristics. RESULTS: The results reveal that Dutch men and
women participate in 24 and 28 minutes of daily physical activity through walking
and cycling, which is 41% and 55% more than the minimum recommended level. It
should be noted however that some 57% of the entire sample failed to record any
walking or cycling, and an investigation of this particular group serves as an
important topic of future research. Active transport was positively related with
age, income, bicycle ownership, urban density and air temperature. Car ownership
had a strong negative relationship with physically active travel. CONCLUSION: The
results of this analysis demonstrate the significance of active transport to
counter the emerging issue of sedentary lifestyle disease. The Dutch experience
provides other countries with a highly relevant case study in the creation of
environments and cultures that support healthy, active living.
PMID- 25849903
TI - Effects of exenatide on postprandial vascular endothelial dysfunction in type 2
diabetes mellitus.
AB - BACKGROUND: Basic studies have shown that glucagon-like peptide-1 (GLP-1) analogs
exert a direct protective effect on the vascular endothelium in addition to their
indirect effects on postprandial glucose and lipid metabolism. GLP-1 analogs are
also reported to inhibit postprandial vascular endothelial dysfunction. This
study examined whether the GLP-1 analog exenatide inhibits postprandial vascular
endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM).
METHODS: Seventeen patients with T2DM underwent a meal tolerance test to examine
changes in postprandial vascular endothelial function and in glucose and lipid
metabolism, both without exenatide (baseline) and after a single subcutaneous
injection of 10 MUg exenatide. Vascular endothelial function was determined using
reactive hyperemia index (RHI) measured by peripheral arterial tonometry before
and 120 min after the meal loading test. The primary endpoint was the difference
in changes in postprandial vascular endothelial function between the baseline and
exenatide tests. RESULTS: The natural logarithmically-scaled RHI (L_RHI) was
significantly lower after the baseline meal test but not in the exenatide test.
The use of exenatide resulted in a significant decrease in triglycerides (TG)
area under the curve and coefficient of variation (CV). The change in L_RHI
correlated with changes in CV of triglycerides and HDL-cholesterol. Multivariate
analysis identified changes in triglyceride CV as the only determinant of changes
in L_RHI, contributing to 41% of the observed change. CONCLUSIONS: Exenatide
inhibited postprandial vascular endothelial dysfunction after the meal loading
test, suggesting that exenatide has a multiphasic anti-atherogenic action
involving not only glucose but also lipid metabolism. TRIAL REGISTRATION:
ClinicalTrials.gov: UMIN000015699.
PMID- 25849906
TI - Correction: stereoscopic analysis of optic nerve head parameters in primary open
angle glaucoma: the glaucoma stereo analysis study.
PMID- 25849905
TI - Brain-derived neurotrophic factor ameliorates learning deficits in a rat model of
Alzheimer's disease induced by abeta1-42.
AB - An emerging body of data suggests that the early onset of Alzheimer's disease
(AD) is associated with decreased brain-derived neurotrophic factor (BDNF).
Because BDNF plays a critical role in the regulation of high-frequency synaptic
transmission and long-term potentiation in the hippocampus, the up-regulation of
BDNF may rescue cognitive impairments and learning deficits in AD. In the present
study, we investigated the effects of hippocampal BDNF in a rat model of AD
produced by a ventricle injection of amyloid-beta1-42 (Abeta1-42). We found that
a ventricle injection of Abeta1-42 caused learning deficits in rats subjected to
the Morris water maze and decreased BDNF expression in the hippocampus. Chronic
intra-hippocampal BDNF administration rescued learning deficits in the water
maze, whereas infusions of NGF and NT-3 did not influence the behavioral
performance of rats injected with Abeta1-42. Furthermore, the BDNF-related
improvement in learning was ERK-dependent because the inhibition of ERK, but not
JNK or p38, blocked the effects of BDNF on cognitive improvement in rats injected
with Abeta1-42. Together, our data suggest that the up-regulation of BDNF in the
hippocampus via activation of the ERK signaling pathway can ameliorate Abeta1-42
induced learning deficits, thus identifying a novel pathway through which BDNF
protects against AD-related cognitive impairments. The results of this research
may shed light on a feasible therapeutic approach to control the progression of
AD.
PMID- 25849907
TI - Periplasmic quality control in biogenesis of outer membrane proteins.
AB - The beta-barrel outer membrane proteins (OMPs) are integral membrane proteins
that reside in the outer membrane of Gram-negative bacteria and perform a diverse
range of biological functions. Synthesized in the cytoplasm, OMPs must be
transported across the inner membrane and through the periplasmic space before
they are assembled in the outer membrane. In Escherichia coli, Skp, SurA and DegP
are the most prominent factors identified to guide OMPs across the periplasm and
to play the role of quality control. Although extensive genetic and biochemical
analyses have revealed many basic functions of these periplasmic proteins, the
mechanism of their collaboration in assisting the folding and insertion of OMPs
is much less understood. Recently, biophysical approaches have shed light on the
identification of the intricate network. In the present review, we summarize
recent advances in the characterization of these key factors, with a special
emphasis on the multifunctional protein DegP. In addition, we present our
proposed model on the periplasmic quality control in biogenesis of OMPs.
PMID- 25849904
TI - Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous
gasotransmitter.
AB - Hydrogen sulfide (H2S) has become recognized as an important signalling molecule
throughout the body, contributing to many physiological and pathological
processes. In recent years, improved methods for measuring H2S levels and the
availability of a wider range of H2S donors and more selective inhibitors of H2S
synthesis have helped to more accurately identify the many biological effects of
this highly reactive gaseous mediator. Animal studies of several H2S-releasing
drugs have demonstrated considerable promise for the safe treatment of a wide
range of disorders. Several such drugs are now in clinical trials.
PMID- 25849908
TI - Molecular simulation studies of hydrophobic gating in nanopores and ion channels.
AB - Gating in channels and nanopores plays a key role in regulating flow of ions
across membranes. Molecular simulations provide a 'computational microscope'
which enables us to examine the physical nature of gating mechanisms at the level
of the single channel molecule. Water enclosed within the confines of a nanoscale
pore may exhibit unexpected behaviour. In particular, if the molecular surfaces
lining the pore are hydrophobic this promotes de-wetting of the pore. De-wetting
is observed as stochastic liquid-vapour transitions within a pore, and may lead
to functional closure of a pore to the flow of ions and/or water. Such behaviour
was first observed in simulations of simple model nanopores and referred to as
'hydrophobic gating'. Simulations of both the nicotinic acetylcholine receptor
and of TWIK-1 potassium channels (the latter alongside experimental studies)
suggest hydrophobic gating may occur in some biological ion channels. Current
studies are focused on designing hydrophobic gates into biomimetic nanopores.
PMID- 25849909
TI - Elucidating ligand binding and channel gating mechanisms in pentameric ligand
gated ion channels by atomistic simulations.
AB - Pentameric ligand-gated ion channels (pLGICs) are important biomolecules that
mediate fast synaptic transmission. Their malfunctions are linked to serious
neuronal disorders and they are major pharmaceutical targets; in invertebrates,
they are involved in insecticide resistance. The complexity of pLGICs and the
limited crystallographic information available prevent a detailed understanding
of how they function. State-of-the-art computational techniques are therefore
crucial to build an accurate picture at the atomic level of the mechanisms which
drive the activation of pLGICs, complementing the available experimental data. We
have used a series of simulation methods, including homology modelling, ligand
protein docking, density functional theory, molecular dynamics and metadynamics,
a powerful scheme for accelerating rare events, with the guidance of mutagenesis
electrophysiology experiments, to explore ligand-binding mechanisms, the effects
of mutations and the potential role of a proline molecular switch for the gating
of the ion channels. Results for the insect RDL receptor, the GABAC receptor, the
5-HT3 receptor and the nicotinic acetylcholine receptor will be reviewed.
PMID- 25849910
TI - High-resolution free energy landscape analysis of protein folding.
AB - The free energy landscape can provide a quantitative description of folding
dynamics, if determined as a function of an optimally chosen reaction coordinate.
The profile together with the optimal coordinate allows one to directly determine
such basic properties of folding dynamics as the configurations of the minima and
transition states, the heights of the barriers, the value of the pre-exponential
factor and its relation to the transition path times. In the present study, we
review the framework, in particular, the approach to determine such an optimal
coordinate, and its application to the analysis of simulated protein folding
dynamics.
PMID- 25849911
TI - The membranes of Gram-negative bacteria: progress in molecular modelling and
simulation.
AB - Molecular modelling and simulations have been employed to study the membranes of
Gram-negative bacteria for over 20 years. Proteins native to these membranes, as
well as antimicrobial peptides and drug molecules have been studied using
molecular dynamics simulations in simple models of membranes, usually only
comprising one lipid species. Thus, traditionally, the simulations have reflected
the majority of in vitro membrane experimental setups, enabling observations from
the latter to be rationalized at the molecular level. In the last few years, the
sophistication and complexity of membrane models have improved considerably, such
that the heterogeneity of the lipid and protein composition of the membranes can
now be considered both at the atomistic and coarse-grain levels of granularity.
Importantly this means relevant biology is now being retained in the models,
thereby linking the in silico and in vivo scenarios. We discuss recent progress
in simulations of proteins in simple lipid bilayers, more complex membrane models
and finally describe some efforts to overcome timescale limitations of atomistic
molecular dynamics simulations of bacterial membranes.
PMID- 25849912
TI - Is the cellular and molecular machinery docile in the stationary phase of
Escherichia coli?
AB - The bacterial cell envelope retains a highly dense cytoplasm. The properties of
the cytoplasm change with the metabolic state of the cell, the logarithmic phase
(log) being highly active and the stationary phase metabolically much slower.
Under the differing growth phases, many different types of stress mechanisms are
activated in order to maintain cellular integrity. One such response in
enterobacteria is the phage shock protein (Psp) response that enables adaptation
to the inner membrane (IM) stress. The Psp system consists of a transcriptional
activator PspF, negative regulator PspA, signal sensors PspBC, with PspA and PspG
acting as effectors. The single molecule imaging of the PspF showed the existence
of dynamic communication between the nucleoid-bound states of PspF and membrane
via negative regulator PspA and PspBC sensors. The movement of proteins in the
cytoplasm of bacterial cells is often by passive diffusion. It is plausible that
the dynamics of the biomolecules differs with the state of the cytoplasm
depending on the growth phase. Therefore, the Psp response proteins might
encounter the densely packed glass-like properties of the cytoplasm in the
stationary phase, which can influence their cellular dynamics and function. By
comparing the properties of the log and stationary phases, we find that the
dynamics of PspF are influenced by the growth phase and may be controlled by the
changes in the cytoplasmic fluidity.
PMID- 25849914
TI - Life in extreme environments: single molecule force spectroscopy as a tool to
explore proteins from extremophilic organisms.
AB - Extremophiles are organisms which survive and thrive in extreme environments. The
proteins from extremophilic single-celled organisms have received considerable
attention as they are structurally stable and functionally active under extreme
physical and chemical conditions. In this short article, we provide an
introduction to extremophiles, the structural adaptations of proteins from
extremophilic organisms and the exploitation of these proteins in industrial
applications. We provide a review of recent developments which have utilized
single molecule force spectroscopy to mechanically manipulate proteins from
extremophilic organisms and the information which has been gained about their
stability, flexibility and underlying energy landscapes.
PMID- 25849913
TI - Probing the kinetic and thermodynamic consequences of the tetraloop/tetraloop
receptor monovalent ion-binding site in P4-P6 RNA by smFRET.
AB - Structured RNA molecules play roles in central biological processes and
understanding the basic forces and features that govern RNA folding kinetics and
thermodynamics can help elucidate principles that underlie biological function.
Here we investigate one such feature, the specific interaction of monovalent
cations with a structured RNA, the P4-P6 domain of the Tetrahymena ribozyme. We
employ single molecule FRET (smFRET) approaches as these allow determination of
folding equilibrium and rate constants over a wide range of stabilities and thus
allow direct comparisons without the need for extrapolation. These experiments
provide additional evidence for specific binding of monovalent cations, Na+ and
K+, to the RNA tetraloop-tetraloop receptor (TL-TLR) tertiary motif. These ions
facilitate both folding and unfolding, consistent with an ability to help order
the TLR for binding and further stabilize the tertiary contact subsequent to
attainment of the folding transition state.
PMID- 25849915
TI - Modelling biomacromolecular assemblies with continuum mechanics.
AB - We have developed a continuum mechanical description of proteins using a finite
element algorithm which has been generalized to include thermal fluctuations and
which is therefore known as fluctuating finite element analysis (FFEA). Whereas
conventional molecular dynamics (MD) simulations provide a trajectory in which
each individual atomic position fluctuates, a FFEA trajectory shows how the
overall shape of the protein changes due to thermal agitation. We describe the
theoretical background to FFEA, its relationship to more established biomolecular
modelling methods and provide examples of its application to the mesoscale
biomolecular dynamics of the molecular motor dynein.
PMID- 25849916
TI - Enzymatic protein depalmitoylation by acyl protein thioesterases.
AB - Protein palmitoylation is a dynamic post-translational modification, where the 16
carbon fatty acid, palmitate, is added to cysteines of proteins to modulate
protein sorting, targeting and signalling. Palmitate removal from proteins is
mediated by acyl protein thioesterases (APTs). Although initially identified as
lysophospholipases, increasing evidence suggests APT1 and APT2 are the major APTs
that mediate the depalmitoylation of diverse cellular substrates. Here, we
describe the conserved functions of APT1 and APT2 across organisms and discuss
the possibility that these enzymes are members of a larger family of
depalmitoylation enzymes.
PMID- 25849917
TI - Postsynaptic nanodomains generated by local palmitoylation cycles.
AB - Precise regulation of protein assembly at specialized membrane domains is
essential for diverse cellular functions including synaptic transmission.
However, it is incompletely understood how protein clustering at the plasma
membrane is initiated, maintained and controlled. Protein palmitoylation, a
common post-translational modification, regulates protein targeting to the plasma
membrane. Such modified proteins are enriched in these specialized membrane
domains. In this review, we focus on palmitoylation of PSD-95, which is a major
postsynaptic scaffolding protein and makes discrete postsynaptic nanodomains in a
palmitoylation-dependent manner and discuss a determinant role of local
palmitoylation cycles in creating highly localized hotspots at the membrane where
specific proteins concentrate to organize functional domains.
PMID- 25849918
TI - Aberrant palmitoylation in Huntington disease.
AB - Huntington disease (HD) is an adult-onset neurodegenerative disease caused by a
CAG expansion in the HTT gene. HD is characterized by striatal atrophy and is
associated with motor, cognitive and psychiatric deficits. In the presence of the
HD mutation, the interactions between huntingtin (HTT) and huntingtin interacting
protein 14 (HIP14 or DHHC17) and HIP14-like (DHHC13, a HIP14 orthologue),
palmitoyl acyltransferases for HTT, are disturbed, resulting in reduced
palmitoylation of HTT. Genetic ablation of either Hip14 or Hip14l recapitulates
many features of HD, including striatal atrophy and motor deficits. However,
there are no changes in palmitoylation of HTT in either mouse model and,
subsequently, the similarities between the phenotypes of these two mouse models
and the HD mouse model are believed to result from underpalmitoylation of other
HIP14 and HIP14L substrates. HTT acts as a modulator of HIP14 activity such that
in the presence of the HD mutation, HIP14 is less active. Consequently, HIP14
substrates are less palmitoylated, leading to neuronal toxicity. This suggests
that altered HIP14-HTT and HIP14L-HTT interactions in the presence of the HD
mutation reduces palmitoylation and promotes mislocalization of HTT and other
HIP14/HIP14L substrates. Ultimately, HD may be, in part, a disease of altered
palmitoylation.
PMID- 25849920
TI - The zDHHC family of S-acyltransferases.
AB - The discovery of the zDHHC family of S-acyltransferase enzymes has been one of
the major breakthroughs in the S-acylation field. Now, more than a decade since
their discovery, major questions centre on profiling the substrates of individual
zDHHC enzymes (there are 24 ZDHHC genes and several hundred S-acylated proteins),
defining the mechanisms of enzyme-substrate specificity and unravelling the
importance of this enzyme family for cellular physiology and pathology.
PMID- 25849919
TI - Wnt acylation and its functional implication in Wnt signalling regulation.
AB - Wnt proteins are conserved signalling molecules that have an essential role in
regulating diverse processes during embryogenesis and adult tissue homoeostasis.
Wnts are post-translationally modified by palmitoylation, which is essential for
Wnt secretion and function. Intriguingly, the crystal structure of XWnt8 in
complex with the extracellular domain of the Frizzled 8 cysteine-rich domain
(Fzd8-CRD) revealed that Wnts use the fatty acid as a 'hotspot' residue to engage
its receptor, which is a unique mode of receptor-ligand recognition. In addition,
there are several lines of evidence suggesting that Wnts engage several
signalling modulators and alternative receptors by means of fatty acids as a
critical contact residue. In the present article, we review our current
understanding of Wnt acylation and its functional role in Wnt signalling
regulation.
PMID- 25849922
TI - Post-translational myristoylation at the cross roads of cell death, autophagy and
neurodegeneration.
AB - In a little more than a decade, post-translational myristoylation (PTMyr) has
become an established post-translational modification during cell death. It
involves the addition of the fatty acid myristate to newly exposed N-terminal
glycines following caspase cleavage. It promotes membrane binding and
relocalization of functional protein domains released by caspase cleavage during
apoptosis, or programmed cell death. However, as the requirement of caspase
cleavage has expanded beyond just cell death, it has become apparent that PTMyr
may play a role in cell survival, differentiation and now autophagy. Herein, we
describe how myristoylation may play a role in autophagy with an emphasis on
PTMyr.
PMID- 25849921
TI - How many lives does CLIMP-63 have?
AB - In 1995, in the Biochemical Society Transactions, Mundy published the first
review on CLIMP-63 (cytoskeleton-linking membrane protein 63) or CKPA4
(cytoskeleton-associated protein 4), initially just p63 [1]. Here we review the
following 20 years of research on this still mysterious protein. CLIMP-63 is a
type II transmembrane protein, the cytosolic domain of which has the capacity to
bind microtubules whereas the luminal domain can form homo-oligomeric complexes,
not only with neighbouring molecules but also, in trans, with CLIMP-63 molecules
on the other side of the endoplasmic reticulum (ER) lumen, thus promoting the
formation of ER sheets. CLIMP-63 however also appears to have a life at the cell
surface where it acts as a ligand-activated receptor. The still rudimentary
information of how CLIMP-63 fulfills these different roles, what these are
exactly and how post-translational modifications control them, will be discussed.
PMID- 25849924
TI - Palmitoylation and palmitoyl-transferases in Plasmodium parasites.
AB - Protein post-translational modifications (PTM) are commonly used to regulate
biological processes. Protein S-acylation is an enzymatically regulated
reversible modification that has been shown to modulate protein localization,
activity and membrane binding. Proteome-scale discovery on Plasmodium falciparum
schizonts has revealed a complement of more than 400 palmitoylated proteins,
including those essential for host invasion and drug resistance. The wide
regulatory affect on this species is endorsed by the presence of 12 proteins
containing the conserved DHHC-CRD (DHHC motif within a cysteine-rich domain) that
is associated with palmitoyl-transferase activity. Genetic interrogation of these
enzymes in Apicomplexa has revealed essentiality and distinct localization at
cellular compartments; these features are species specific and are not observed
in yeast. It is clear that palmitoylation has an elaborate role in Plasmodium
biology and opens intriguing questions on the functional consequence of this
group of acylation modifications and how the protein S-acyl transferases (PATs)
orchestrate molecular events.
PMID- 25849923
TI - Fatty acyl donor selectivity in membrane bound O-acyltransferases and communal
cell fate decision-making.
AB - The post-translational modification of proteins with lipid moieties confers
spatial and temporal control of protein function by restricting their subcellular
distribution or movement in the extracellular milieu. Yet, little is known about
the significance of lipid selectivity to the activity of proteins targeted for
such modifications. Membrane bound O-acyl transferases (MBOATs) are a superfamily
of multipass enzymes that transfer fatty acids on to lipid or protein substrates.
Three MBOATs constitute a subfamily with secreted signalling molecules for
substrates, the Wnt, Hedgehog (Hh) and Ghrelin proteins. Given their important
roles in adult tissue homoeostasis, all three molecules and their respective
associated acyltransferases provide a framework for interrogating the role of
extracellular acylation events in cell-to-cell communication. Here, we discuss
how the preference for a fatty acyl donor in the Wnt acyltransferase porcupine
(Porcn) and possibly in other protein lipidation enzymes may provide a means for
coupling metabolic health at the single cell level to communal cell fate decision
making in complex multicellular organisms.
PMID- 25849925
TI - Membrane bound O-acyltransferases and their inhibitors.
AB - Since the identification of the membrane-bound O-acyltransferase (MBOATs) protein
family in the early 2000s, three distinct members [porcupine (PORCN), hedgehog
(Hh) acyltransferase (HHAT) and ghrelin O-acyltransferase (GOAT)] have been shown
to acylate specific proteins or peptides. In this review, topology determination,
development of assays to measure enzymatic activities and discovery of small
molecule inhibitors are compared and discussed for each of these enzymes.
PMID- 25849926
TI - Chemical reporters for exploring protein acylation.
AB - Proteins are acylated by a variety of metabolites that regulates many important
cellular pathways in all kingdoms of life. Acyl groups in cells can vary in
structure from the smallest unit, acetate, to modified long-chain fatty acids,
all of which can be activated and covalently attached to diverse amino acid side
chains and consequently modulate protein function. For example, acetylation of
Lys residues can alter the charge state of proteins and generate new recognition
elements for protein-protein interactions. Alternatively, long-chain fatty
acylation targets proteins to membranes and enables spatial control of cell
signalling. To facilitate the analysis of protein acylation in biology, acyl
analogues bearing alkyne or azide tags have been developed that enable
fluorescent imaging and proteomic profiling of modified proteins using
bioorthogonal ligation methods. Herein, we summarize the currently available
acylation chemical reporters and highlight their utility to discover and quantify
the roles of protein acylation in biology.
PMID- 25849927
TI - Cholesterylation: a tail of hedgehog.
AB - Cholesterylation is a post-translational attachment of sterol to proteins. This
modification has been a characteristic of a single family of hedgehog proteins
(Hh). Hh is a well-established morphogenic molecule important in embryonic
development. It was also found to be involved in the progression of many cancer
types. Herein, we describe the mechanism of biosynthesis of cholesterylated Hh,
the role of this unusual modification on protein functions and novel chemical
probes, which could be used to specifically target this modification, both in
vitro and in vivo.
PMID- 25849928
TI - Activation of the E3 ubiquitin ligase Parkin.
AB - The PINK1 (phosphatase and tensin homologue-induced putative kinase 1)/Parkin
dependent mitochondrial quality control pathway mediates the clearance of damaged
organelles, but appears to be disrupted in Parkinson's disease (PD) [Springer and
Kahle (2011) Autophagy 7, 266-278]. Upon mitochondrial stress, PINK1 activates
the E3 ubiquitin (Ub) ligase Parkin through phosphorylation of the Ub-like (UBL)
domain of Parkin and of the small modifier Ub itself at a conserved residue
[Sauve and Gehring (2014) Cell Res. 24, 1025-1026]. Recently resolved partial
crystal structures of Parkin showed a 'closed', auto-inhibited conformation,
consistent with its notoriously weak enzymatic activity at steady state [Wauer
and Komander (2013) EMBO J. 32, 2099-2112; Riley et al. (2013) Nat. Commun. 4,
1982; Trempe et al. (2013) Science 340, 1451-1455; Spratt et al. (2013) Nat.
Commun. 4, 1983]. It has thus become clear that Parkin must undergo major
structural rearrangements in order to unleash its catalytic functions. Recent
published findings derived from X-ray structures and molecular modelling present
a complete structural model of human Parkin at an all-atom resolution [Caulfield
et al. (2014) PLoS Comput. Biol. 10, e1003935]. The results of the combined in
silico simulations-based and experimental assay-based study indicates that PINK1
dependent Ser65 phosphorylation of Parkin is required for its activation and
triggering of 'opening' conformations. Indeed, the obtained structures showed a
sequential release of Parkin's intertwined domains and allowed docking of an Ub
charged E2 coenzyme, which could enable its enzymatic activity. In addition,
using cell-based screening, select E2 enzymes that redundantly, cooperatively or
antagonistically regulate Parkin's activation and/or enzymatic functions at
different stages of the mitochondrial autophagy (mitophagy) process were
identified [Fiesel et al. (2014) J. Cell Sci. 127, 3488-3504]. Other work that
aims to pin-point the particular pathogenic dysfunctions of Parkin mis-sense
mutations have been recently disseminated (Fabienne C. Fiesel, Thomas R.
Caulfield, Elisabeth L. Moussaud-Lamodiere, Daniel F.A.R. Dourado, Kotaro Ogaki,
Owen A. Ross, Samuel C. Flores, and Wolfdieter Springer, submitted). Such a
structure-function approach provides the basis for the dissection of Parkin's
regulation and a targeted drug design to identify small-molecule activators of
this neuroprotective E3 Ub ligase.
PMID- 25849929
TI - Stimulation of electron transport as potential novel therapy in Parkinson's
disease with mitochondrial dysfunction.
AB - Parkinson's disease (PD) is a neurodegenerative motor disorder characterized by
the loss of dopaminergic neurons. This loss of dopaminergic neurons is the
pathological hallmark of the disease that results in the characteristic motor
syndrome. Restoration of dopamine levels is the basis of current therapy;
however, this does not tackle the cause of the disease. While the aetiology of PD
remains mostly elusive, mitochondrial dysfunction has been linked to (at least)
part of the PD cases. In this review we discuss recent findings in Drosophila
melanogaster showing that stimulation of the electron transport chain is
beneficial for PD fly models showing Complex I defects and discuss the possible
clinical applications of these findings.
PMID- 25849930
TI - PINK1 activation-turning on a promiscuous kinase.
AB - PINK1 [phosphatase and tensin homologue (PTEN)-induced putative kinase 1] is a
serine/threonine kinase targeted to mitochondria and implicated in early-onset
recessive Parkinson's disease (PD). Through the phosphorylation of its downstream
targets, PINK1 regulates multiple mitochondrial processes, including ATP
production, stress-response and mitochondrial dynamics and quality control. The
orchestration of such a wide array of functions by an individual kinase requires
a fine-tuned and versatile regulation of its activity. PINK1 proteolytic
processing, trafficking and localization, as well as different post-translational
modifications, affect its activity and function. Unravelling the regulatory
mechanisms of PINK1 is essential for a full comprehension of its kinase function
in health and disease.
PMID- 25849931
TI - Biochemical properties of the kinase PINK1 as sensor protein for mitochondrial
damage signalling.
AB - Defects of mitochondrial functions have been implicated in many different human
diseases, in particular neurodegenerative diseases. The kinase PINK1 [phosphatase
and tensin homologue (PTEN)-induced kinase 1] has been identified as a crucial
player in a specific damage signalling pathway, eliminating defective
mitochondria by an autophagic process. Mutations in PINK1 have been shown to
cause familial cases of Parkinson's disease. In this review, we summarize the
biochemical mechanisms that underlie the association of PINK1 with mitochondria
under normal and pathological conditions. This unconventional mitochondrial
localization pathway is discussed in the context of the role of PINK1 as a sensor
of mitochondrial damage and a causative factor in Parkinson's disease.
PMID- 25849932
TI - Linking microtubules to Parkinson's disease: the case of parkin.
AB - Microtubules (MTs) are dynamic polymers consisting of alpha/beta tubulin dimers
and playing a plethora of roles in eukaryotic cells. Looking at neurons, they are
key determinants of neuronal polarity, axonal transport and synaptic plasticity.
The concept that MT dysfunction can participate in, and perhaps lead to,
Parkinson's disease (PD) progression has been suggested by studies using toxin
based and genetic experimental models of the disease. Here, we first learn
lessons from MPTP and rotenone as well as from the PD related genes, including
SNCA and LRRK2, and then look at old and new evidence regarding the interplay
between parkin and MTs. Data from experimental models and human cells point out
that parkin regulates MT stability and strengthen the link between MTs and PD
paving the way to a viable strategy for the management of the disease.
PMID- 25849933
TI - The endoplasmic reticulum/mitochondria interface: a subcellular platform for the
orchestration of the functions of the PINK1-Parkin pathway?
AB - Mitochondrial dysfunction is a hallmark of both idiopathic and familial
Parkinson's disease (PD). Mutations in the PARK2 and PARK6 genes, coding for the
cytosolic E3 ubiquitin protein ligase Parkin and the mitochondrial
serine/threonine kinase PINK1 [phosphatase and tensin homologue (PTEN)-induced
putative kinase 1], lead to clinically similar early-onset Parkinsonian
syndromes. PINK1 and Parkin cooperate within a conserved pathway to preserve
mitochondrial quality through the regulation of a variety of processes, including
mitochondrial dynamics, transport, bioenergetics, biogenesis and turnover. The
molecular mechanisms behind the orchestration of this plethora of functions
remain poorly understood. In the present review, we emphasize the functional
overlap between the PINK1-Parkin pathway and the endoplasmic reticulum (ER)
mitochondria interface, a subcellular compartment critically involved in
neurodegeneration. We discuss how this compartment may constitute a hub for the
spatiotemporal organization of the activities of the PINK1-Parkin pathway.
PMID- 25849934
TI - iPS models of Parkin and PINK1.
AB - Parkinson disease (PD) is a degenerative disorder of the central nervous system
resulting from depletion of dopaminergic neurons and currently remains incurable
despite enormous international research efforts. The development of induced
pluripotent stem cell (iPSC) technology opened up the unique possibility of
studying disease mechanisms in human tissue that was otherwise not accessible,
such as the brain. Of particular interest are the monogenetic forms of PD as they
closely resemble the more common 'idiopathic' PD and, through the mutated
protein, provide a clear research target in iPSC-derived neurons. Recessively
inherited Parkin and PTEN-induced putative kinase 1 (PINK1) mutations have been
investigated in this context and the present review describes the first insights
gained from studies in iPSC-derived dopaminergic neurons, which comprise
abnormalities in mitochondrial and dopamine homoeostasis, microtubular stability
and axonal outgrowth. These new models of PD have a high translational potential
that includes the identification of druggable targets, testing of known and novel
therapeutic agents in the disease-relevant tissue using well-defined read-outs
and potential regenerative approaches.
PMID- 25849935
TI - GSHSite: exploiting an iteratively statistical method to identify s
glutathionylation sites with substrate specificity.
AB - S-glutathionylation, the covalent attachment of a glutathione (GSH) to the sulfur
atom of cysteine, is a selective and reversible protein post-translational
modification (PTM) that regulates protein activity, localization, and stability.
Despite its implication in the regulation of protein functions and cell
signaling, the substrate specificity of cysteine S-glutathionylation remains
unknown. Based on a total of 1783 experimentally identified S-glutathionylation
sites from mouse macrophages, this work presents an informatics investigation on
S-glutathionylation sites including structural factors such as the flanking amino
acids composition and the accessible surface area (ASA). TwoSampleLogo presents
that positively charged amino acids flanking the S-glutathionylated cysteine may
influence the formation of S-glutathionylation in closed three-dimensional
environment. A statistical method is further applied to iteratively detect the
conserved substrate motifs with statistical significance. Support vector machine
(SVM) is then applied to generate predictive model considering the substrate
motifs. According to five-fold cross-validation, the SVMs trained with substrate
motifs could achieve an enhanced sensitivity, specificity, and accuracy, and
provides a promising performance in an independent test set. The effectiveness of
the proposed method is demonstrated by the correct identification of previously
reported S-glutathionylation sites of mouse thioredoxin (TXN) and human protein
tyrosine phosphatase 1b (PTP1B). Finally, the constructed models are adopted to
implement an effective web-based tool, named GSHSite
(http://csb.cse.yzu.edu.tw/GSHSite/), for identifying uncharacterized GSH
substrate sites on the protein sequences.
PMID- 25849936
TI - The amelioration of hepatic steatosis by thyroid hormone receptor agonists is
insufficient to restore insulin sensitivity in ob/ob mice.
AB - Thyroid hormone receptor (TR) agonists have been proposed as therapeutic agents
to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We
investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic
steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride
levels and ameliorated hepatic steatosis. However, the amelioration of fatty
liver was not sufficient to improve insulin sensitivity in these mice and
reductions in hepatic triglycerides did not correlate with improvements in
insulin sensitivity or glycemic control. Instead, the effects of TR activation on
glycemia varied widely and were found to depend upon the time of treatment as
well as the compound and dosage used. Lower doses of GC-1 were found to further
impair glycemic control, while a higher dose of the same compound resulted in
substantially improved glucose tolerance and insulin sensitivity, despite all
doses being equally effective at reducing hepatic triglyceride levels.
Improvements in glycemic control and insulin sensitivity were observed only in
treatments that also increased body temperature, suggesting that the induction of
thermogenesis may play a role in mediating these beneficial effects. These data
illustrate that the relationship between TR activation and insulin sensitivity is
complex and suggests that although TR agonists may have value in treating NAFLD,
their effect on insulin sensitivity must also be considered.
PMID- 25849937
TI - Structural variation discovery in the cancer genome using next generation
sequencing: computational solutions and perspectives.
AB - Somatic Structural Variations (SVs) are a complex collection of chromosomal
mutations that could directly contribute to carcinogenesis. Next Generation
Sequencing (NGS) technology has emerged as the primary means of interrogating the
SVs of the cancer genome in recent investigations. Sophisticated computational
methods are required to accurately identify the SV events and delineate their
breakpoints from the massive amounts of reads generated by a NGS experiment. In
this review, we provide an overview of current analytic tools used for SV
detection in NGS-based cancer studies. We summarize the features of common SV
groups and the primary types of NGS signatures that can be used in SV detection
methods. We discuss the principles and key similarities and differences of
existing computational programs and comment on unresolved issues related to this
research field. The aim of this article is to provide a practical guide of
relevant concepts, computational methods, software tools and important factors
for analyzing and interpreting NGS data for the detection of SVs in the cancer
genome.
PMID- 25849938
TI - Inhibition of BET bromodomains as a therapeutic strategy for cancer drug
discovery.
AB - As a conserved protein interaction module that recognizes and binds to acetylated
lysine, bromodomain (BRD) contains a deep, largely hydrophobic acetyl lysine
binding site. Proteins that share the feature of containing two BRDs and an extra
terminal domain belong to BET family, including BRD2, BRD3, BRD4 and BRDT. BET
family proteins perform transcription regulatory function under normal
conditions, while in cancer, they regulate transcription of several oncogenes,
such as c-Myc and Bcl-2. Thus, targeting BET proteins may be a promising
strategy, and intense interest of BET proteins has fueled the development of
structure-based bromodomain inhibitors in cancer. In this review, we focus on
summarizing several small-molecule BET inhibitors and their relevant anti-tumor
mechanisms, which would provide a clue for exploiting new targeted BET inhibitors
in the future cancer therapy.
PMID- 25849939
TI - Combination of carbon ion beam and gemcitabine causes irreparable DNA damage and
death of radioresistant pancreatic cancer stem-like cells in vitro and in vivo.
AB - We try to elucidate whether a carbon ion beam alone or in combination with
gemcitabine has advantages over X-ray in targeting putative pancreatic cancer
stem-like cells (CSCs) in vitro and in vivo. Colony, spheroid formation and
tumorigenicity assays confirmed that CD44+/ESA+ cells sorted from PANC1 and PK45
cells have more CSC properties than CD44-/ESA- cells. The number of colonies and
spheroids formed from CSCs after carbon ion beam irradiation was significantly
reduced compared to after X-ray irradiation, and they were extremely highly
suppressed when carbon ion beam combined with gemcitabine. The relative
biological effectiveness (RBE) values for the carbon ion beam relative to X-ray
at the D10 levels for CSCs were 2.23-2.66. Expressions of multiple cell death
related genes were remarkably highly induced, and large numbers of gammaH2AX foci
in CSCs were formed after carbon ion beam combined with gemcitabine. The highly
expressed CSC markers were significantly inhibited after 30 Gy of carbon ion beam
and almost lost after 25 Gy carbon ion beam combined with 50 mg/kg gemcitabine.
In conclusion, a carbon ion beam combined with gemcitabine has superior potential
to kill pancreatic CSCs via irreparable clustered DSB compared to a carbon ion
alone or X-rays combined with gemcitabine.
PMID- 25849940
TI - Clostridium novyi-NT can cause regression of orthotopically implanted
glioblastomas in rats.
AB - Glioblastoma (GBM) is a highly aggressive primary brain tumor that is especially
difficult to treat. The tumor's ability to withstand hypoxia leads to enhanced
cancer cell survival and therapy resistance, but also yields a microenvironment
that is in many aspects unique within the human body, thus offering potential
therapeutic opportunities. The spore-forming anaerobic bacterium Clostridium
novyi-NT(C. novyi-NT) has the ability to propagate in tumor-generated hypoxia,
leading to oncolysis. Here, we show that intravenously injected spores of C.
novyi-NT led to dramatic tumor destructions and significant survival increases in
implanted, intracranial syngeneic F98 and human xenograft 060919 rat GBM models.
C. novyi-NT germination was specific and confined to the neoplasm, with sparing
of the normal brain parenchyma. All animals tolerated the bacteriolytic
treatment, but edema and increased intracranial pressure could quickly be lethal
if not monitored and medically managed with hydration and antibiotics. These
results provide pre-clinical data supporting the development of this therapeutic
approach for the treatment of patients with GBM.
PMID- 25849941
TI - Transforming growth factor-beta pathway activity in glioblastoma.
AB - Transforming growth factor (TGF)-beta is a central molecule maintaining the
malignant phenotype of glioblastoma. Anti-TGF-beta strategies are currently being
explored in early clinical trials. Yet, there is little contemporary data on the
differential expression of TGF-beta isoforms at the mRNA and protein level or TGF
beta/Smad pathway activity in glioblastomas in vivo.Here we studied 64 newly
diagnosed and 16 recurrent glioblastomas for the expression of TGF-beta1-3,
platelet-derived growth factor (PDGF)-B, and plasminogen activator inhibitor
(PAI)-1 mRNA by RT-PCR and for the levels of TGF-beta1-3 protein, phosphorylated
Smad2 (pSmad2), pSmad1/5/8 and PAI-1 by immunohistochemistry.Among the TGF-beta
isoforms, TGF-beta1 mRNA was the most, whereas TGF-beta3 mRNA was the least
abundant. TGF-beta1-3 mRNA expression was strongly correlated, as was the
expression of TGF-beta1-3 mRNA, and of the TGF-beta1-3 target genes, PDGF-B and
PAI-1. TGF-beta2 and TGF-beta3 protein levels correlated well, whereas the
comparison of the other TGF-betaisoforms did not. Positive correlation was also
observed between TGF-beta1 and pSmad1/5/8 and between pSmad2 and pSmad1/5/8.
Survival analyses indicated that a group of patients with high expression levels
of TGF-beta2 mRNA or pSmad1/5/8 protein have inferior outcome.We thus provide
potential biomarkers for patient stratification in clinical trials of anti-TGF
beta therapies in glioblastoma.
PMID- 25849942
TI - Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs.
AB - Anti-angiogenic therapies were approved for different cancers. However,
significant primary and secondary resistance hampers efficacy in several tumor
types including breast cancer. Thus, we need to develop clinically applicable
strategies to enhance efficacy of anti-angiogenic drugs.We report that anti
angiogenic therapies can induce upregulation of cyclooxygenase-2 (Cox-2) and of
its product prostaglandin E2 (PGE2) in breast cancer models. Upon Cox-2
inhibition PGE2 levels were normalized and efficacy of anti-vascular endothelial
growth factor receptor 2 (anti-VEGFR-2) antibodies and sunitinib was enhanced.
Interestingly, both treatments exerted additive anti-angiogenic effects.
Following Cox-2 inhibition, we observed reduced infiltration of tumors with
cancer-associated fibroblasts (CAFs) and lower levels of pro-angiogenic factors
active besides the VEGF axis including hepatocyte growth factor (HGF) and basic
fibroblast growth factor (FGF2). Mechanistic studies indicated that Cox-2
inhibition reduced PGE2-induced migration and proliferation of CAFs via
inhibiting phosphorylation of Akt.Hence, Cox-2 inhibition can increase efficacy
of anti-angiogenic treatments and our findings might pave the road for clinical
investigations of concomitant blockade of Cox-2 and VEGF-signaling.
PMID- 25849943
TI - MicroRNA-3127 promotes cell proliferation and tumorigenicity in hepatocellular
carcinoma by disrupting of PI3K/AKT negative regulation.
AB - Recent studies have shown that multiple phosphatases deactivate the PI3K/AKT
signaling pathway. Here we demonstrated that, by suppressing multiple
phosphatases, miR-3127 promotes growth of hepatocellular carcinoma (HCC). Our
study also reveals clinical significance of miR-3127 expression in HCC patients.
MiR-3127 expression was markedly upregulated in HCC tissues and cells.
Furthermore, high miR-3127 expression was associated with an aggressive phenotype
and poor prognosis. MiR-3127 overexpression promoted HCC cell proliferation in
vitro and tumor growth in vivo. Also, miR-3127 accelerated G1-S transition by
activating AKT/ FOXO1 signaling, by directly targeting the 3' untranslated
regions (3'UTR) of pleckstrin homology domain leucine-rich repeat protein
phosphatase 1/2 (PHLPP1/2), inositol polyphosphate phosphatase 4A (INPP4A), and
inositol polyphosphate-5-phosphatase J (INPP5J) mRNA, repressing their
expression. In agreement, the miRNA antagonist antagomir-3127 suppressed HCC cell
proliferation and tumor growth by inhibiting the AKT/FOXO1 signaling. Taken
together, these findings suggest that silencing miR-3127 might be a potential
therapeutic strategy.
PMID- 25849944
TI - Chronic iron deficiency as an emerging risk factor for osteoporosis: a
hypothesis.
AB - Iron is essential in oxygen transport and participates in many enzymatic systems
in the body, with important roles in collagen synthesis and vitamin D metabolism.
The relationship between iron and bone health comes from clinical observations in
iron overload patients who suffered bone loss. The opposite scenario--whether
iron deficiency, with or without anemia, affects bone metabolism--has not been
fully addressed. This is of great interest, as this nutrient deficiency is a
worldwide public health problem and at the same time osteoporosis and bone
alterations are highly prevalent. This review presents current knowledge on
nutritional iron deficiency and bone remodeling, the biomarkers to evaluate iron
status and bone formation and resorption, and the link between iron and bone
metabolism. Finally, it is hypothesized that chronic iron deficiency induces bone
resorption and risk of osteoporosis, thus complete recovery from anemia and its
prevention should be promoted in order to improve quality of life including bone
health. Several mechanisms are suggested; hence, further investigation on the
possible impact of chronic iron deficiency on the development of osteoporosis is
needed.
PMID- 25849945
TI - Estimated daily intake and seasonal food sources of quercetin in Japan.
AB - Quercetin is a promising food component, which can prevent lifestyle related
diseases. To understand the dietary intake of quercetin in the subjects of a
population-based cohort study and in the Japanese population, we first determined
the quercetin content in foods available in the market during June and July in or
near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained
high amounts of quercetin derivatives. We then estimated the daily quercetin
intake by 570 residents aged 20-92 years old in the town using a food frequency
questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5
mg day(-1), respectively. The quercetin intakes by men were lower than those by
women; the quercetin intakes showed a low correlation with age in both men and
women. The estimated quercetin intake was similar during summer and winter.
Quercetin was mainly ingested from onions and green tea, both in summer and in
winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf
lettuce, were good sources of quercetin in summer. Our results will help to
elucidate the association between quercetin intake and risks of lifestyle-related
diseases by further prospective cohort study and establish healthy dietary
requirements with the consumption of more physiologically useful components from
foods.
PMID- 25849946
TI - Unique features of high-density lipoproteins in the Japanese: in population and
in genetic factors.
AB - Despite its gradual increase in the past several decades, the prevalence of
atherosclerotic vascular disease is low in Japan. This is largely attributed to
difference in lifestyle, especially food and dietary habits, and it may be
reflected in certain clinical parameters. Plasma high-density lipoprotein (HDL)
levels, a strong counter risk for atherosclerosis, are indeed high among the
Japanese. Accordingly, lower HDL seems to contribute more to the development of
coronary heart disease (CHD) than an increase in non-HDL lipoproteins at a
population level in Japan. Interestingly, average HDL levels in Japan have
increased further in the past two decades, and are markedly higher than in
Western populations. The reasons and consequences for public health of this
increase are still unknown. Simulation for the efficacy of raising HDL
cholesterol predicts a decrease in CHD of 70% in Japan, greater than the extent
by reducing low-density lipoprotein cholesterol predicted by simulation or
achieved in a statin trial. On the other hand, a substantial portion of
hyperalphalipoproteinemic population in Japan is accounted for by genetic
deficiency of cholesteryl ester transfer protein (CETP), which is also commonly
unique in East Asian populations. It is still controversial whether CETP
mutations are antiatherogenic. Hepatic Schistosomiasis is proposed as a potential
screening factor for historic accumulation of CETP deficiency in East Asia.
PMID- 25849947
TI - Maternal dietary patterns during pregnancy in relation to offspring forearm
fractures: prospective study from the Danish National Birth Cohort.
AB - Limited evidence exists for an association between maternal diet during pregnancy
and offspring bone health. In a prospective study, we examined the association
between dietary patterns in mid-pregnancy and offspring forearm fractures. In
total, 101,042 pregnancies were recruited to the Danish National Birth Cohort
(DNBC) during 1996-2002. Maternal diet was collected by a food frequency
questionnaire. Associations were analyzed between seven dietary patterns
extracted by principal component analysis and offspring first occurrence of any
forearm fracture diagnosis, extracted from the Danish National Patient Register,
between time of birth and end of follow-up (< 16 year) (n = 53,922). In
multivariable Cox regression models, offspring of mothers in the fourth vs. first
quintile of the Western pattern had a significant increased risk (Hazard ratio,
95% confidence interval: 1.11, 1.01-1.23) of fractures, and there was a
borderline significant positive trend (p = 0.06). The other dietary patterns
showed no associations and neither did supplementary analyses of macro- and
micronutrients or single food groups, except for the intake of artificially
sweetened soft drinks, which was positively associated with offspring forearm
fractures (p = 0.02). In the large prospective DNBC high mid-pregnancy
consumption of Western diet and artificially sweetened soft drinks, respectively,
indicated positive associations with offspring forearm fractures, which provides
interesting hypotheses for future research.
PMID- 25849948
TI - Low maternal vitamin B12 status is associated with lower cord blood HDL
cholesterol in white Caucasians living in the UK.
AB - BACKGROUND AND AIMS: Studies in South Asian population show that low maternal
vitamin B12 associates with insulin resistance and small for gestational age in
the offspring. Low vitamin B12 status is attributed to vegetarianism in these
populations. It is not known whether low B12 status is associated with metabolic
risk of the offspring in whites, where the childhood metabolic disorders are
increasing rapidly. Here, we studied whether maternal B12 levels associate with
metabolic risk of the offspring at birth. METHODS: This is a cross-sectional
study of 91 mother-infant pairs (n = 182), of white Caucasian origin living in
the UK. Blood samples were collected from white pregnant women at delivery and
their newborns (cord blood). Serum vitamin B12, folate, homocysteine as well as
the relevant metabolic risk factors were measured. RESULTS: The prevalence of low
serum vitamin B12 (<191 ng/L) and folate (<4.6 MUg/L) were 40% and 11%,
respectively. Maternal B12 was inversely associated with offspring's Homeostasis
Model Assessment 2-Insulin Resistance (HOMA-IR), triglycerides, homocysteine and
positively with HDL-cholesterol after adjusting for age and BMI. In regression
analysis, after adjusting for likely confounders, maternal B12 is independently
associated with neonatal HDL-cholesterol and homocysteine but not triglycerides
or HOMA-IR. CONCLUSIONS: Our study shows that low B12 status is common in white
women and is independently associated with adverse cord blood cholesterol.
PMID- 25849949
TI - Role of dietary protein and thiamine intakes on cognitive function in healthy
older people: a systematic review.
AB - The effectiveness of nutritional interventions to prevent and maintain cognitive
functioning in older adults has been gaining interest due to global population
ageing. A systematic literature review was conducted to obtain and appraise
relevant studies on the effects of dietary protein or thiamine on cognitive
function in healthy older adults. Studies that reported on the use of nutritional
supplementations and/or populations with significant cognitive impairment were
excluded. Seventeen eligible studies were included. Evidence supporting an
association between higher protein and/or thiamine intakes and better cognitive
function is weak. There was no evidence to support the role of specific protein
food sources, such as types of meat, on cognitive function. Some cross-sectional
and case-control studies reported better cognition in those with higher dietary
thiamine intakes, but the data remains inconclusive. Adequate protein and
thiamine intake is more likely associated with achieving a good overall
nutritional status which affects cognitive function rather than single nutrients.
A lack of experimental studies in this area prevents the translation of these
dietary messages for optimal cognitive functioning and delaying the decline in
cognition with advancing age.
PMID- 25849950
TI - Hepatoprotective effect of herb formula KIOM2012H against nonalcoholic fatty
liver disease.
AB - Nonalcoholic fatty liver disease (NAFLD) is a hepatic ailment with a rapidly
increasing incidence due to dietary hypernutrition and subsequent obesity. Fatty
liver disease can lead to steatohepatitis, fibrosis, cirrhosis, and even cancer,
which is associated with various complications. Discovering effective natural
materials and herbs can provide alternative and complementary medical treatments
to current chemical pharmaceuticals. To develop an effective natural agent for
NAFLD, we formulated a combination of four herb mixtures (KIOM2012H) and observed
lipid-lowering efficacy. The inhibitory effects of KIOM2012H on free fatty acid
induced lipid accumulation, triglyceride contents, and gene expressions were
analyzed in HepG2 cells. Using high fat diet-fed mice, body weight changes, gross
liver appearances, hepatic triglyceride contents, and gene expressions were
evaluated. KIOM2012H dose-dependently inhibited lipid accumulation and gene
expressions involved in lipogenesis and related regulators. Experimental animals
also showed a decrease in body weight changes and lipid-associated physiological
parameters. This study shows that KIOM2012H has an alleviating effect on fatty
acid and lipid accumulation, and therefore can be applied for development of new
therapeutic pharmaceuticals for treatment of NAFLD using natural products and
herbs.
PMID- 25849951
TI - Atorvastatin reduces long pentraxin 3 expression in vascular cells by inhibiting
protein geranylgeranylation.
AB - BACKGROUND: The long pentraxin PTX3 is an acute-phase multi-functional protein
that might play both positive and detrimental effects under different
pathophysiological conditions. We previously showed that statins down-regulate
the release of PTX3 in human endothelial cells (ECs). The present study
investigated the mechanism mediating this effect, its occurrence in other cells
involved in atherogenesis, and whether it takes place in experimental
atherosclerosis. METHODS AND RESULTS: We found that atorvastatin (1-5 MUmol/L)
decreased the production and release of PTX3 in human ECs through a post
transcriptional effect. Co-incubation with mevalonate or geranylgeranyl
pyrophosphate prevented this effect. Direct blockade of geranylgeranyl
transferase I by GGTI-286, treatment with the Rac inhibitor NSC23766 or silencing
of the geranylgeranylated GTPase Rac2 by siRNA closely mimicked the action of
atorvastatin. In contrast, inactivation of other geranylgeranylated proteins such
as RhoA, RhoB, and RhoC or Rac1 did not affect PTX3 release. In addition, we
found that atorvastatin also decreased PTX3 secretion in aortic SMCs through a
mechanism likely dependent on protein geranylgeranylation, while no effect was
observed in monocytes. Finally, we found that atherosclerotic lesions from
cholesterol-fed rabbits treated with atorvastatin (2.5 mg/kg/day for 8 weeks)
showed less immunoreactive PTX3 than lesions from control animals. CONCLUSIONS:
Results suggest that statins may interfere with PTX3 expression in vascular cells
via inhibition of protein geranylgeranylation. Since PTX3 is increasingly
regarded as an important mediator of the inflammatory response underlying
atherosclerosis and its complications, these results highlight the need for
further studies of the role of PTX3 and its potential pharmacological modulation
in cardiovascular disease.
PMID- 25849953
TI - Photochemical activation of drugs for the treatment of therapy-resistant cancers.
AB - Resistance to chemotherapy, molecular targeted therapy as well as radiation
therapy is a major obstacle for cancer treatment. Cancer resistance may be
exerted through multiple different mechanisms which may be orchestrated as
observed in multidrug resistance (MDR). Cancer resistance may be intrinsic or
acquired and often leaves patients without any treatment options. Strategies for
alternative treatment modalities for resistant cancer are therefore highly
warranted. Photochemical internalization (PCI) is a technology for cytosolic
delivery of macromolecular therapeutics based on the principles of photodynamic
therapy (PDT). The present report reviews the current knowledge of PCI of therapy
resistant cancers. In summary, PCI may be able to circumvent several of the major
mechanisms associated with resistance towards chemotherapeutics including
increased expression of drug efflux pumps, altered intracellular drug
distribution and increased ROS scavenging. Current data also suggest PCI of
targeted toxins as highly effective in cancers resistant to clinically available
targeted therapy such as monoclonal antibodies (mAbs) and tyrosine kinase
inhibitors (TKIs). PCI may therefore, in general, represent a future treatment
option for cancers resistant to other therapies.
PMID- 25849952
TI - Myricitrin attenuates endothelial cell apoptosis to prevent atherosclerosis: An
insight into PI3K/Akt activation and STAT3 signaling pathways.
AB - Blood vessel endothelial dysfunction induced by oxidized low-density lipoprotein
(ox-LDL) has been implicated in the pathogenesis of atherosclerosis and
vasculopathy. The ox-LDL-elicited reactive oxygen species (ROS) release has been
assumed to serve a critical function in endothelial damage. Myricitrin (from
Myrica cerifera) is a natural antioxidant that has strong anti-oxidative, anti
inflammatory, and anti-nociceptive activities. However, the protective effect of
myricitrin on ROS-induced endothelial cell injury and its related molecular
mechanisms have never been investigated. This study demonstrates that myricitrin
can inhibit ox-LDL-induced endothelial apoptosis and prevent plaque formation at
an early stage in an atherosclerotic mouse model. The administration of
myricitrin in vivo decreases the thickness of the vascular wall in the aortic
arch of ApoE-/- mice. In vitro study shows that ox-LDL-induced human umbilical
vein endothelial cell apoptosis can be reduced upon receiving myricitrin pre
treatment. Treatment with myricitrin significantly attenuated ox-LDL-induced
endothelial cell apoptosis by inhibiting LOX-1 expression and by increasing the
activation of the STAT3 and PI3K/Akt/eNOS signaling pathways. At the same time,
our result demonstrates that myricitrin treatment optimizes the balance of
pro/anti-apoptosis proteins, including Bax, Bad, XIAP, cIAP-2, and survivin. Our
study suggests that myricitrin treatment can effectively protect cells from ox
LDL-induced endothelial cell apoptosis, which results in reduced atherosclerotic
plaque formation. This result indicates that myricitrin can be used as a drug
candidate for the treatment of cardiovascular diseases.
PMID- 25849954
TI - Microarray analysis identifies IL-1 receptor type 2 as a novel candidate
biomarker in patients with acute respiratory distress syndrome.
AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is a disease associated
with a high mortality rate. The initial phase is characterized by induction of
inflammatory cytokines and chemokines and influx of circulating inflammatory
cells, including macrophages which play a pivotal role in the innate and adaptive
immune responses to injury. Growing evidence points to phenotypic heterogeneity
and plasticity between various macrophage activation states. METHODS: In this
study, gene expression in alveolar macrophages and circulating leukocytes from
healthy control subjects and patients with ARDS was assessed by mRNA microarray
analysis. RESULTS: Both alveolar macrophages and circulating leukocytes
demonstrated up-regulation of genes encoding chemotactic factors, antimicrobial
peptides, chemokine receptors, and matrix metalloproteinases. Two genes, the pro
inflammatory S100A12 and the anti-inflammatory IL-1 decoy receptor IL-1R2 were
significantly induced in both cell populations in ARDS patients, which was
confirmed by protein quantification. Although S100A12 levels did not correlate
with disease severity, there was a significant association between early plasma
levels of IL-1R2 and APACHE III scores at presentation. Moreover, higher levels
of IL-1R2 in plasma were observed in non-survivors as compared to survivors at
later stages of ARDS. CONCLUSIONS: These results suggest a hybrid state of
alveolar macrophage activation in ARDS, with features of both alternative
activation and immune tolerance/deactivation.. Furthermore, we have identified a
novel plasma biomarker candidate in ARDS that correlates with the severity of
systemic illness and mortality.
PMID- 25849955
TI - Enhancement of reproductive heat tolerance in plants.
AB - Comparison of average crop yields with reported record yields has shown that
major crops exhibit annual average yields three- to seven-fold lower than record
yields because of unfavorable environments. The current study investigated the
enhancement of pollen heat tolerance through expressing an Arabidopsis thaliana
heat shock protein 101 (AtHSP101) that is not normally expressed in pollen but
reported to play a crucial role in vegetative thermotolerance. The AtHSP101
construct under the control of the constitutive ocs/mas 'superpromoter' was
transformed into cotton Coker 312 and tobacco SRI lines via Agrobacterium
mediated transformation. Thermotolerance of pollen was evaluated by in vitro
pollen germination studies. Comparing with those of wild type and transgenic null
lines, pollen from AtHSP101 transgenic tobacco and cotton lines exhibited
significantly higher germination rate and much greater pollen tube elongation
under elevated temperatures or after a heat exposure. In addition, significant
increases in boll set and seed numbers were also observed in transgenic cotton
lines exposed to elevated day and night temperatures in both greenhouse and field
studies. The results of this study suggest that enhancing heat tolerance of
reproductive tissues in plant holds promise in the development of crops with
improved yield production and yield sustainability in unfavorable environments.
PMID- 25849956
TI - Inclined to see it your way: Do altercentric intrusion effects in visual
perspective taking reflect an intrinsically social process?
AB - It has been suggested that some aspects of mental state understanding recruit a
rudimentary, but fast and efficient, processing system, demonstrated by the
obligatory slowing down of judgements about what the self can see when this is
incongruent with what another can see. We tested the social nature of this system
by investigating to what extent these altercentric intrusions are elicited under
conditions that differed in their social relevance and, further, how these
related to self-reported social perspective taking and empathy. In Experiment 1,
adult participants were asked to make "self" or "other" perspective-taking
judgements during congruent ("self" and "other" can see the same items) or
incongruent conditions ("self" and "other" cannot see the same items) in
conditions that were social (i.e., involving a social agent), semisocial (an
arrow), or nonsocial (a dual-coloured block). Reaction time indices of
altercentric intrusion effects were present across all conditions, but were
significantly stronger for the social than for the less social conditions. Self
reported perspective taking and empathy correlated with altercentric intrusion
effects in the social condition only. In Experiment 2, the significant
correlations for the social condition were replicated, but this time with gaze
duration indices of altercentric intrusion effects. Findings are discussed with
regard to the degree to which this rudimentary system is socially specialized and
how it is linked to more conceptual understanding.
PMID- 25849957
TI - Second German-Catalan workshop on epigenetics & cancer.
AB - The Second German-Catalan Workshop on Epigenetics and Cancer was held in
Barcelona on November 19-21, 2014. The workshop brought together, for the second
time, scientists from 2 German and 2 Catalan research institutions: the DKFZ,
from Heidelberg, the CRCME, from Freiburg, and the IMPPC and PEBC/IDIBELL, both
from Barcelona. The German-Catalan Workshops are intended to establish the
framework for building a Research School to foster collaborations between
researchers from the different institutions. Exchange programs for graduate
students are among the activities of the future School. The topics presented and
discussed in 33 talks were diverse and included work on DNA methylation, histone
modifications, chromatin biology, characterization of imprinted regions in human
tissues, non-coding RNAs, and epigenetic drug discovery. Among novel developments
from the previous Workshop are the report of the epigenetics angle of the Warburg
effect and the long-range trans-acting interaction of DNA methylation and of
nucleosome remodeling. A shift in the view on DNA methylation became apparent by
the realization of the intertwined interplay between hyper- and hypo-methylation
in differentiation and cancer.
PMID- 25849958
TI - Asymmetry of deep medullary veins on susceptibility weighted MRI in patients with
acute MCA stroke is associated with poor outcome.
AB - BACKGROUND AND PURPOSE: Due to its sensitivity to deoxyhemoglobin, susceptibility
weighted imaging (SWI) enables the visualization of deep medullary veins (DMV) in
patients with acute stroke, which are difficult to depict under physiological
circumstances. This study assesses the asymmetric appearance of prominent DMV as
an independent predictor for stroke severity and outcome. MATERIALS AND METHODS:
SWI of 86 patients with acute middle cerebral artery (MCA) stroke were included.
A scoring system from 0 (no visible DMV) to 3 (very prominent DMV) was applied
for both hemispheres separately. A difference of scores between ipsi- and
contralateral side was defined as asymmetric (AMV+). Occurrence of AMV+ was
correlated with the National Institute of Health Stroke Scale (NIHSS) Score on
admission and discharge, as well as the modified Rankin Scale (mRS) at discharge.
Ordinal regression analysis was used to evaluate NIHSS and mRS as predictors of
stroke severity, clinical course of disease and outcome. RESULTS: 55 patients
displayed AMV+ while 31 did not show an asymmetry (AMV-). Median NIHSS on
admission was 17 (11-21) in the AMV+ group and 9 (5-15) in the AMV- group (p =
0.001). On discharge median NIHSS was 11 (5-20) for AMV+ and 5 (2-14) for AMV- (p
= 0.005). The median mRS at discharge was 4 (3-5) in the AMV+ group and 3 (1-4)
in AMV- (p = 0.001). Odds ratio was 3.19 (95% CI: 1.24-8.21) for AMV+ to achieve
a higher mRS than AMV- (p = 0.016). CONCLUSION: The asymmetric appearance of DMV
on SWI is a fast and easily evaluable parameter for the prediction of stroke
severity and can be used as an additional imaging parameter in patients with
acute MCA stroke.
PMID- 25849959
TI - Assessing species boundaries using multilocus species delimitation in a
morphologically conserved group of neotropical freshwater fishes, the Poecilia
sphenops species complex (Poeciliidae).
AB - Accurately delimiting species is fundamentally important for understanding
species diversity and distributions and devising effective strategies to conserve
biodiversity. However, species delimitation is problematic in many taxa,
including 'non-adaptive radiations' containing morphologically cryptic lineages.
Fortunately, coalescent-based species delimitation methods hold promise for
objectively estimating species limits in such radiations, using multilocus
genetic data. Using coalescent-based approaches, we delimit species and infer
evolutionary relationships in a morphologically conserved group of Central
American freshwater fishes, the Poecilia sphenops species complex. Phylogenetic
analyses of multiple genetic markers (sequences of two mitochondrial DNA genes
and five nuclear loci) from 10/15 species and genetic lineages recognized in the
group support the P. sphenops species complex as monophyletic with respect to
outgroups, with eight mitochondrial 'major-lineages' diverged by >=2% pairwise
genetic distances. From general mixed Yule-coalescent models, we discovered
(conservatively) 10 species within our concatenated mitochondrial DNA dataset, 9
of which were strongly supported by subsequent multilocus Bayesian species
delimitation and species tree analyses. Results suggested species-level diversity
is underestimated or overestimated by at least ~15% in different lineages in the
complex. Nonparametric statistics and coalescent simulations indicate
genealogical discordance among our gene tree results has mainly derived from
interspecific hybridization in the nuclear genome. However, mitochondrial DNA
show little evidence for introgression, and our species delimitation results
appear robust to effects of this process. Overall, our findings support the
utility of combining multiple lines of genetic evidence and broad
phylogeographical sampling to discover and validate species using coalescent
based methods. Our study also highlights the importance of testing for
hybridization versus incomplete lineage sorting, which aids inference of not only
species limits but also evolutionary processes influencing genetic diversity.
PMID- 25849960
TI - Mortality related to acute illness and injury in rural Uganda: task shifting to
improve outcomes.
AB - BACKGROUND: Due to the dual critical shortages of acute care and healthcare
workers in resource-limited settings, many people suffer or die from conditions
that could be easily treated if existing resources were used in a more timely and
effective manner. In order to address this preventable morbidity and mortality, a
novel emergency midlevel provider training program was developed in rural Uganda.
This is the first study that assesses this unique application of a task-shifting
model to acute care by evaluating the outcomes of 10,105 patients. METHODS:
Nurses participated in a two-year training program to become midlevel providers
called Emergency Care Practitioners at a rural district hospital. This is a
retrospective analysis of the Emergency Department's quality assurance database,
including three-day follow-up data. Case fatality rates (CFRs) are reported as
the percentage of cases with a specific diagnosis that died within three days of
their Emergency Department visit. FINDINGS: Overall, three-day mortality was
2.0%. The most common diagnoses of patients who died were malaria (n=60),
pneumonia (n=51), malnutrition (n=21), and trauma (n=18). Overall and under-five
CFRs were as follows: malaria, 2.0% and 1.9%; pneumonia, 5.5% and 4.1%; and
trauma, 1.2% and 1.6%. Malnutrition-related fatality (all cases <18 years old)
was 6.5% overall and 6.8% for under-fives. INTERPRETATION: This study describes
the outcomes of emergency patients treated by midlevel providers in a resource
limited setting. Our fatality rates are lower than previously published regional
rates. These findings suggest this model of task-shifting can be successfully
applied to acute care in order to address the shortage of emergency care services
in similar settings as part of an integrated approach to health systems
strengthening.
PMID- 25849961
TI - Recurrence After Primary Pterygium Excision: Amniotic Membrane Transplantation
with Fibrin Glue Versus Conjunctival Autograft with Fibrin Glue.
AB - PURPOSE: The aim of the present study was to compare the surgical results and
recurrence rates of primary pterygium excision with conjunctival autografts
versus amniotic membrane grafts fixated with fibrin glue. MATERIALS AND METHODS:
In this prospective study, 73 eyes of 65 patients who had undergone conjunctival
autograft group (CAG) (n:37) or amniotic membrane group (AMG) (n:36) after
pterygium excision were evaluated. Fibrin glue was used for the fixation of
grafts in both groups. The patients were followed up for 12 months. Postoperative
complications were recorded. The rate of recurrence was defined as the primary
outcome measure. RESULTS: In the CAG, partial dehiscence of the graft was
observed on the nasal edge on postoperative day 1 in two (5.4%) eyes that healed
with secondary re-epithelialization at week 1. Twelve (32.4%) eyes showed a
yellowish-orange or hemorrhagic edema of the graft on postoperative day 7 that
spontaneously resolved in 1 to 3 weeks. In the AMG, partial dehiscence and
folding of the amniotic membrane occurred in two (5.5%) eyes. Two eyes (5.4 %) in
the CAG developed corneal recurrence and five eyes (13.8%) in the amniotic
membrane graft group developed recurrence; one limbal (2.7%), four corneal
recurrences (11.1%) (p = 0.25). CONCLUSION: Fibrin glue is a safe and effective
method for attaching conjunctival or amniotic membrane grafts for wound closure
following pterygium surgery. Although the results were not statistically
significant, amniotic membrane grafting using fibrin glue seems to have a higher
pterygium recurrence rate compared with conjunctival autografting.
PMID- 25849962
TI - Home foreclosure, health, and mental health: a systematic review of individual,
aggregate, and contextual associations.
AB - BACKGROUND: The U.S. foreclosure crisis intensified markedly during the Great
Recession of 2007-09, and currently an estimated five percent of U.S. residential
properties are more than 90 days past due or in the process of foreclosure. Yet
there has been no systematic assessment of the effects of foreclosure on health
and mental health. METHODS AND FINDINGS: I applied systematic search terms to
PubMed and PsycINFO to identify quantitative or qualitative studies about the
relationship between home foreclosure and health or mental health. After
screening the titles and abstracts of 930 publications and reviewing the full
text of 76 articles, dissertations, and other reports, I identified 42
publications representing 35 unique studies about foreclosure, health, and mental
health. The majority of studies (32 [91%]) concluded that foreclosure had adverse
effects on health or mental health, while three studies yielded null or mixed
findings. Only two studies examined the extent to which foreclosure may have
disproportionate impacts on ethnic or racial minority populations. CONCLUSIONS:
Home foreclosure adversely affects health and mental health through channels
operating at multiple levels: at the individual level, the stress of personally
experiencing foreclosure was associated with worsened mental health and adverse
health behaviors, which were in turn linked to poorer health status; at the
community level, increasing degradation of the neighborhood environment had
indirect, cross-level adverse effects on health and mental health. Early
intervention may be able to prevent acute economic shocks from eventually
developing into the chronic stress of foreclosure, with all of the attendant
benefits this implies for health and mental health status. Programs designed to
encourage early return of foreclosed properties back into productive use may have
similar health and mental health benefits.
PMID- 25849963
TI - Long-term outcomes of percutaneous cryoablation for patients with hepatocellular
carcinoma within Milan criteria.
AB - BACKGROUND: Accumulating evidences have suggested that percutaneous cryoablation
could be a valuable alternative ablation therapy for HCC but there has been no
large cohort-based analysis on its long-term outcomes. METHODS: A series of 866
patients with Child-Pugh class A-B cirrhosis and HCC within Milan criteria who
underwent percutaneous cryoablation was long-term followed. The safety, efficacy,
5-year survival, and prognostic factors of percutaneous cryoablation in the
treatment of HCC were analyzed. RESULTS: A total of 1197 HCC lesions were ablated
with 1401 cryoablation sessions. Complete response (CR) was achieved in 1163
(97.2%) lesions and 832 (96.1%) patients with 34 (2.8%) major complications, but
no treatment-related mortality. After a median of 30.9 months follow-up, 502
(60.3%) patients who achieved CR developed different types of recurrence. The
cumulative local tumor recurrence rate was 24.2% at 5-years. Multiple tumor
lesions, tumor size > 3 cm, and repeated ablation of same lesion were independent
risk factors associated with local recurrence. The 5-year overall survival (OS)
rates were 59.5%. Age < 36 years, HCC family history, baseline hepatitis B virus
DNA >106 copies/ml, and three HCC lesions were independently and significantly
negative predictors to the post-cryoablation OS. CONCLUSIONS: Percutaneous
cryoablation is an effective therapy for patients with HCC within Milan criteria,
with comparable efficacy, safety and long-term survival to the reported outcomes
of radiofrequency ablation.
PMID- 25849964
TI - Evaluation and validation of housekeeping genes as reference for gene expression
studies in pigeonpea (Cajanus cajan) under drought stress conditions.
AB - Gene expression analysis using quantitative real-time PCR (qRT-PCR) is a very
sensitive technique and its sensitivity depends on the stable performance of
reference gene(s) used in the study. A number of housekeeping genes have been
used in various expression studies in many crops however, their expression were
found to be inconsistent under different stress conditions. As a result, species
specific housekeeping genes have been recommended for different expression
studies in several crop species. However, such specific housekeeping genes have
not been reported in the case of pigeonpea (Cajanus cajan) despite the fact that
genome sequence has become available for the crop. To identify the stable
housekeeping genes in pigeonpea for expression analysis under drought stress
conditions, the relative expression variations of 10 commonly used housekeeping
genes (EF1alpha, UBQ10, GAPDH, 18SrRNA, 25SrRNA, TUB6, ACT1, IF4alpha, UBC and
HSP90) were studied on root, stem and leaves tissues of Asha (ICPL 87119). Three
statistical algorithms geNorm, NormFinder and BestKeeper were used to define the
stability of candidate genes. geNorm analysis identified IF4alpha and TUB6 as the
most stable housekeeping genes however, NormFinder analysis determined IF4alpha
and HSP90 as the most stable housekeeping genes under drought stress conditions.
Subsequently validation of the identified candidate genes was undertaken in qRT
PCR based gene expression analysis of uspA gene which plays an important role for
drought stress conditions in pigeonpea. The relative quantification of the uspA
gene varied according to the internal controls (stable and least stable genes),
thus highlighting the importance of the choice of as well as validation of
internal controls in such experiments. The identified stable and validated
housekeeping genes will facilitate gene expression studies in pigeonpea
especially under drought stress conditions.
PMID- 25849965
TI - Characterization of pediatric hospital-associated infection caused by methicillin
resistant Staphylococcus aureus in mainland China.
AB - BACKGROUND: This study was conducted to investigate the clinical features of
hospital-associated infections (HAIs) caused by methicillin-resistant
Staphylococcus aureus (MRSA) in Chinese children, and the molecular
characteristics of the bacteria. METHODS: Patients with HAIs caused by MRSA were
identified retrospectively. All isolates were analyzed using molecular typing and
antimicrobial susceptibility tests. RESULTS: In total, 150 patients were
identified, with a median age of 18 months. The most common infection was
pneumonia (55.3%), followed by skin and soft tissue infections (46%). Invasive
infections were observed in 52 patients (34.7%), and their hospital stay was
longer compared with non-invasive cases (21 vs 12 days, p = 0.047). A total of 16
sequence types (STs) were identified. ST239 and ST59 were common clones,
accounting for 46% and 28% of cases, respectively. Compared with cases caused by
ST239-SCCmecI-III, patients infected by ST59-SCCmecIV-V had a lower median age
(11 vs 41 months, p = 0.047) and more commonly developed invasive infection (50%
vs 18.8%, p = 0.006). CONCLUSIONS: Invasive infections accounted for a large
proportion of HAIs caused by MRSA. ST59-SCCmecIV/V, a common clone in the
community, caused HAIs in Chinese children, more often infected younger children
and caused invasive infections.
PMID- 25849967
TI - Photochromic phenoxyl-imidazolyl radical complexes with decoloration rates from
tens of nanoseconds to seconds.
AB - We report a novel photochromic molecular system, phenoxyl-imidazolyl radical
complex (PIC), in which both a phenoxyl radical site and an imidazolyl radical
site are reversibly and simultaneously generated upon UV light irradiation. PIC
consists of the three parts: an aromatic linker, a diarylimidazole moiety, and a
4H-cyclohexadienone ring. Upon UV light irradiation, the C-N bond between the 4H
cyclohexadienone ring and the imidazole ring in the colorless closed-ring isomer
of PIC undergoes a homolytic cleavage, leading to the formation of the transient
colored open-ring isomer. Based on the substituents on the imidazoyl/4H
cyclohexadienone rings and the nature of the aromatic linker, the half-life of
the colored open-ring isomer can be varied between tens of nanoseconds and
seconds. PIC derivatives containing a 1,2-phenylene linker exhibit high fatigue
resistance toward repeated photochromic reactions. Analysis using laser flash
photolysis reveals that the absorption spectra of the open-ring isomers are not
readily rationalized by a straightforward superposition of the spectra of the two
component radical fragments and the photogenerated radicals are electronically
coupled through the aromatic linker. Furthermore, the open-ring isomer can be
treated as a hybrid of the pure open-shell biradical and closed-shell quinoid
resonance structures.
PMID- 25849966
TI - Mechanisms of endocrine resistance in breast cancer: an overview of the proposed
roles of noncoding RNA.
AB - Endocrine therapies such as tamoxifen and aromatase inhibitors are the standard
treatment options for estrogen receptor-positive breast cancer patients. However,
resistance to these agents has become a major clinical obstacle. Potential
mechanisms of resistance to endocrine therapies have been identified, often
involving enhanced growth factor signaling and changes in the expression or
action of the estrogen receptor, but few studies have addressed the role of
noncoding RNA (ncRNA). Two important types of ncRNA include microRNA (miRNA) and
long noncoding RNA (lncRNA). miRNAs are small RNA molecules that regulate gene
expression via translational inhibition or degradation of mRNA transcripts, while
lncRNAs are larger RNA molecules that have been shown to play a role in multiple
cellular maintenance functions such as protein scaffolding, chromatin looping,
and regulation of mRNA stability. Both miRNA and lncRNA have recently impacted
the field of breast cancer research as important pieces in the mechanistic puzzle
of the genes and pathways involved in breast cancer development and progression.
This review serves as an overview of the roles of miRNA and lncRNA in breast
cancer progression and the development of endocrine resistance. Ideally, future
experiments in the field should include identification of ncRNAs that could be
potential therapeutic targets in endocrine-resistant tumors, as well as ncRNA
biomarkers that facilitate more tumor-specific treatment options for endocrine
resistant breast cancer patients.
PMID- 25849968
TI - Examination of the Mild Brain Injury Atypical Symptom Scale and the Validity-10
Scale to detect symptom exaggeration in US military service members.
AB - OBJECTIVE: The purpose of this study was to examine the clinical utility of two
validity scales designed for use with the Neurobehavioral Symptom Inventory (NSI)
and the PTSD Checklist-Civilian Version (PCL-C); the Mild Brain Injury Atypical
Symptoms Scale (mBIAS) and Validity-10 scale. METHOD: Participants were 63 U.S.
military service members (age: M = 31.9 years, SD = 12.5; 90.5% male) who
sustained a mild traumatic brain injury (MTBI) and were prospectively enrolled
from Walter Reed National Military Medical Center. Participants were divided into
two groups based on the validity scales of the Minnesota Multiphasic Personality
Inventory-2 Restructured Form (MMPI-2-RF): (a) symptom validity test (SVT)-Fail
(n = 24) and (b) SVT-Pass (n = 39). Participants were evaluated on average 19.4
months postinjury (SD = 27.6). RESULTS: Participants in the SVT-Fail group had
significantly higher scores (p < .05) on the mBIAS (d = 0.85), Validity-10 (d =
1.89), NSI (d = 2.23), and PCL-C (d = 2.47), and the vast majority of the MMPI-2
RF scales (d = 0.69 to d = 2.47). Sensitivity, specificity, and predictive power
values were calculated across the range of mBIAS and Validity-10 scores to
determine the optimal cutoff to detect symptom exaggeration. For the mBIAS, a
cutoff score of >=8 was considered optimal, which resulted in low sensitivity
(.17), high specificity (1.0), high positive predictive power (1.0), and moderate
negative predictive power (.69). For the Validity-10 scale, a cutoff score of
>=13 was considered optimal, which resulted in moderate-high sensitivity (.63),
high specificity (.97), and high positive (.93) and negative predictive power
(.83). CONCLUSION: These findings provide strong support for the use of the
Validity-10 as a tool to screen for symptom exaggeration when administering the
NSI and PCL-C. The mBIAS, however, was not a reliable tool for this purpose and
failed to identify the vast majority of people who exaggerated symptoms.
PMID- 25849969
TI - An automated clinical alert system for newly-diagnosed atrial fibrillation.
AB - OBJECTIVE: Clinical decision support systems that notify providers of abnormal
test results have produced mixed results. We sought to develop, implement, and
evaluate the impact of a computer-based clinical alert system intended to improve
atrial fibrillation stroke prophylaxis, and identify reasons providers do not
implement a guideline-concordant response. MATERIALS AND METHODS: We conducted a
cohort study with historical controls among patients at a tertiary care hospital.
We developed a decision rule to identify newly-diagnosed atrial fibrillation,
automatically notify providers, and direct them to online evidence-based
management guidelines. We tracked all notifications from December 2009 to
February 2010 (notification period) and applied the same decision rule to all
patients from December 2008 to February 2009 (control period). Primary outcomes
were accuracy of notification (confirmed through chart review) and prescription
of warfarin within 30 days. RESULTS: During the notification period 604
notifications were triggered, of which 268 (44%) were confirmed as newly
diagnosed atrial fibrillation. The notifications not confirmed as newly-diagnosed
involved patients with no recent electrocardiogram at our institution. Thirty
four of 125 high-risk patients (27%) received warfarin in the notification
period, compared with 34 of 94 (36%) in the control period (odds ratio, 0.66 [95%
CI, 0.37-1.17]; p = 0.16). Common reasons to not prescribe warfarin (identified
from chart review of 151 patients) included upcoming surgical procedure, choice
to use aspirin, and discrepancy between clinical notes and the medication record.
CONCLUSIONS: An automated system to identify newly-diagnosed atrial fibrillation,
notify providers, and encourage access to management guidelines did not change
provider behaviors.
PMID- 25849970
TI - IL-21R signaling suppresses IL-17+ gamma delta T cell responses and production of
IL-17 related cytokines in the lung at steady state and after Influenza A virus
infection.
AB - Influenza A virus (IAV) infection of the respiratory tract elicits a robust
immune response, which is required for efficient virus clearance but at the same
time can contribute to lung damage and enhanced morbidity. IL-21 is a member of
the type I cytokine family and has many different immune-modulatory functions
during acute and chronic virus infections, although its role in IAV infection has
not been fully evaluated. In this report we evaluated the contributions of IL
21/IL-21 receptor (IL-21R) signaling to host defense in a mouse model of primary
IAV infection using IL-21R knock out (KO) mice. We found that lack of IL-21R
signaling had no significant impact on virus clearance, adaptive T cell
responses, or myeloid cell accumulations in the respiratory tract. However, a
subset of inflammatory cytokines were elevated in the bronchoalveolar lavage
fluid of IL-21R KO mice, including IL-17. Although there was only a small
increase in Th17 cells in the lungs of IL-21R KO mice, we observed a dramatic
increase in gamma delta (gammadelta) T cells capable of producing IL-17 both
after IAV infection and at steady state in the respiratory tract. Finally, we
found that IL-21R signaling suppressed the accumulation of IL-17+ gammadelta T
cells in the respiratory tract intrinsically. Thus, our study reveals a
previously unrecognized role of IL-21R signaling in regulating IL-17 production
by gammadelta T cells.
PMID- 25849971
TI - Dietary galacto-oligosaccharides prevent airway eosinophilia and
hyperresponsiveness in a murine house dust mite-induced asthma model.
AB - BACKGROUND: Allergic asthma is strongly associated with the exposure to house
dust mite (HDM) and is characterized by eosinophilic pulmonary inflammation and
airway hyperresponsiveness (AHR). Recently, there is an increased interest in
using dietary oligosaccharides, also known as prebiotics, as a novel strategy to
prevent the development of, or reduce, symptoms of allergy. AIM: We investigated
the preventive capacity of dietary galacto-oligosaccharides (GOS) compared to an
intra-airway therapeutic treatment with budesonide on the development of HDM
induced allergic asthma in mice. METHODS: BALB/c mice were intranasally
sensitized with 1 MUg HDM on day 0 followed by daily intranasal challenge with
PBS or 10 MUg HDM on days 7 to 11. Two weeks prior to the first sensitization and
throughout the experiment mice were fed a control diet or a diet containing 1%
GOS. Reference mice were oropharyngeally instilled with budesonide (500 MUg/kg)
on days 7, 9, 11, and 13, while being fed the control diet. On day 14, AHR was
measured by nebulizing increasing doses of methacholine into the airways. At the
end of the experiment, bronchoalveolar lavage fluid (BALF) and lungs were
collected. RESULTS: Sensitization and challenge with HDM resulted in AHR. In
contrast to budesonide, dietary intervention with 1% GOS prevented the
development of AHR. HDM sensitization and challenge resulted in a significant
increase in BALF leukocytes numbers, which was suppressed by budesonide treatment
and dietary intervention with 1% GOS. Moreover, HDM sensitization and challenge
resulted in significantly enhanced concentrations of IL-6, CCL17, IL-33, CCL5 and
IL-13 in lung tissue. Both dietary intervention with 1% GOS or budesonide
treatment significantly decreased the HDM-induced increased concentrations of
CCL5 and IL-13 in lung tissue, while budesonide also reduced the HDM-enhanced
concentrations of IL-6 and CCL17 in lung tissue. CONCLUSION: Not only did dietary
intervention with 1% GOS during sensitization and challenge prevent the induction
of airway eosinophilia and Th2-related cytokine and chemokine concentrations in
the lung equally effective as budesonide treatment, it also prevented AHR
development in HDM-allergic mice. GOS might be useful for the prevention and/or
treatment of symptoms in asthmatic disease.
PMID- 25849972
TI - One-step immunoassay for tetrabromobisphenol a using a camelid single domain
antibody-alkaline phosphatase fusion protein.
AB - Tetrabromobisphenol A (TBBPA) is a ubiquitous brominated flame retardant, showing
widespread environmental and human exposures. A variable domain of the heavy
chain antibody (VHH), naturally occurring in camelids, approaches the lower size
limit of functional antigen-binding entities. The ease of genetic manipulation
makes such VHHs a superior choice to use as an immunoreagent. In this study, a
highly selective anti-TBBPA VHH T3-15 fused with alkaline phosphatase (AP) from
E. coli was expressed, showing both an integrated TBBPA-binding capacity and
enzymatic activity. A one-step immunoassay based on the fusion protein T3-15-AP
was developed for TBBPA in 5% dimethyl sulfoxide (DMSO)/phosphate buffered saline
(PBS, pH 7.4), with a half-maximum signal inhibition concentration (IC50) of 0.20
ng mL(-1). Compared to the parental VHH T3-15, T3-15-AP was able to bind to a
wider variety of coating antigens and the assay sensitivity was slightly
improved. Cross-reactivity of T3-15-AP with a set of important brominated
analogues was negligible (<0.1%). Although T3-15-AP was susceptible to extreme
heat (90 degrees C), much higher binding stability at ambient temperature was
observed in the T3-15-AP-based assay for at least 70 days. A simple pretreatment
method of diluting urine samples with DMSO was developed for a one-step assay.
The recoveries of TBBPA from urine samples via this one-step assay ranged from
96.7% to 109.9% and correlated well with a high-performance liquid chromatography
tandem mass spectroscopy (HPLC-MS/MS) method. It is expected that the dimerized
fusion protein, VHH-AP, will show promising applications in human exposure and
environmental monitoring.
PMID- 25849974
TI - Editorial Comment for Silay et al.
PMID- 25849975
TI - Selective contributions of neuronal and astroglial interleukin-1 receptor 1 to
the regulation of sleep.
AB - Interactions between sleep and immune function are bidirectional. Although the
mechanisms that govern these interactions are not fully elucidated, the pro
inflammatory cytokine, interleukin-1beta (IL-1), is a known regulator of sleep
and mediator of immune responses. To further clarify the underlying substrates of
sleep and immune interactions, we engineered two transgenic mouse lines that
express interleukin-1 receptor 1 (IL1R1) only in the central nervous system (CNS)
and selectively on neurons (NSE-IL1R1) or astrocytes (GFAP-IL1R1). During
spontaneous sleep, compared to wild type (WT) animals, NSE-IL1R1 and GFAP-IL1R1
mice have more rapid eye movement sleep (REMS) that is characterized by reduced
theta power in the electroencephalogram (EEG) spectra. The non-REM sleep (NREMS)
EEG of each of the IL1R1 transgenic mouse strains also is characterized by
enhanced power in the delta frequency band. In response to 6h of sleep
deprivation, sleep of both IL1R1 transgenic mouse strains is more consolidated
than that of WT animals. Additionally, the NREMS EEG of NSE-IL1R1 mice contains
less delta power after sleep deprivation, suggesting astroglial IL1R1 activity
may modulate sleep homeostasis. Intracerebroventricular injection of IL-1 fails
to alter sleep or brain temperature of NSE-IL1R1 or GFAP-IL1R1 mice. These data
suggest that selective IL1R1 expression on neurons or on astrocytes is not
sufficient for centrally-administered IL-1 to induce sleep or fever. Lack of
sleep and febrile responses to IL-1 in these IL1R1 transgenic mouse strains may
be due to their inability to produce IL-6 in brain. Overall, these studies
demonstrate, through the use of novel transgenic mice, that IL1R1 on neurons and
astrocytes differentially mediates aspects of sleep under physiological
conditions and in response to central IL-1 administration.
PMID- 25849976
TI - Sleep and immunity: A growing field with clinical impact.
PMID- 25849977
TI - Latent semantics of action verbs reflect phonetic parameters of intensity and
emotional content.
AB - Conjuring up our thoughts, language reflects statistical patterns of word co
occurrences which in turn come to describe how we perceive the world. Whether
counting how frequently nouns and verbs combine in Google search queries, or
extracting eigenvectors from term document matrices made up of Wikipedia lines
and Shakespeare plots, the resulting latent semantics capture not only the
associative links which form concepts, but also spatial dimensions embedded
within the surface structure of language. As both the shape and movements of
objects have been found to be associated with phonetic contrasts already in
toddlers, this study explores whether articulatory and acoustic parameters may
likewise differentiate the latent semantics of action verbs. Selecting 3 * 20
emotion-, face-, and hand-related verbs known to activate premotor areas in the
brain, their mutual cosine similarities were computed using latent semantic
analysis LSA, and the resulting adjacency matrices were compared based on two
different large scale text corpora: HAWIK and TASA. Applying hierarchical
clustering to identify common structures across the two text corpora, the verbs
largely divide into combined mouth and hand movements versus emotional
expressions. Transforming the verbs into their constituent phonemes, and
projecting them into an articulatory space framed by tongue height and formant
frequencies, the clustered small and large size movements appear differentiated
by front versus back vowels corresponding to increasing levels of arousal.
Whereas the clustered emotional verbs seem characterized by sequences of close
versus open jaw produced phonemes, generating up- or downwards shifts in formant
frequencies that may influence their perceived valence. Suggesting, that the
latent semantics of action verbs reflect parameters of intensity and emotional
polarity that appear correlated with the articulatory contrasts and acoustic
characteristics of phonemes.
PMID- 25849978
TI - Analysis of xyloglucan endotransglycosylase/hydrolase (XTH) genes and diverse
roles of isoenzymes during persimmon fruit development and postharvest softening.
AB - Xyloglucan endotransglycosylase/hydrolase (XTH) enzymes have played a role in the
remodeling of cell wall hemicelluloses. To investigate the function of XTHs in
persimmon (Diospyros kaki L.) fruit development and postharvest softening, five
cDNAs (DkXTH1 to DkXTH5), whose putative proteins contained the conserved
DEIDFEFLG motif of XTH, were cloned. Real time quantitative PCR analysis revealed
that DkXTH1, DkXTH4, and DkXTH5 peaked in immature expanding fruit, and their
higher expression was observed along with higher fruit firmness in cold-treated
fruit or firmer cultivar fruit during storage. The opposite gene expression
patterns were observed in DkXTH2 and DkXTH3, which reached maxima concomitance
with pronounced fruit softening. Meanwhile, the xyloglucan endotransglycosylase
(XET) enzymes play important roles in both the rapid growth and ripening of
persimmon fruit. Furthermore, the recombined DkXTH1 and DkXTH2 proteins showed
significant XET activity without any detected XEH activity. However, the XET
activity of recombined DkXTH2 protein had a higher affinity for small acceptor
molecules than that of recombined DkXTH1 protein. The former might prefer to
participate in cell wall restructuring, and the latter is more inclined to
participate in cell wall assembly. Besides, DKXTH proteins could function by
targeting to the cell wall under regulation of a signal peptide. The data
suggested that individual DKXTHs could exhibit different patterns of expression,
and the encoded products possessed specific enzymatic properties conferring on
their respective functions in growth and postharvest softening of persimmon
fruit.
PMID- 25849979
TI - Preload-based starling-like control for rotary blood pumps: numerical comparison
with pulsatility control and constant speed operation.
AB - In this study, we evaluate a preload-based Starling-like controller for
implantable rotary blood pumps (IRBPs) using left ventricular end-diastolic
pressure (PLVED) as the feedback variable. Simulations are conducted using a
validated mathematical model. The controller emulates the response of the natural
left ventricle (LV) to changes in PLVED. We report the performance of the preload
based Starling-like controller in comparison with our recently designed
pulsatility controller and constant speed operation. In handling the transition
from a baseline state to test states, which include vigorous exercise, blood loss
and a major reduction in the LV contractility (LVC), the preload controller
outperformed pulsatility control and constant speed operation in all three test
scenarios. In exercise, preload-control achieved an increase of 54% in mean pump
flow ([Formula: see text]) with minimum loading on the LV, while pulsatility
control achieved only a 5% increase in flow and a decrease in mean pump speed. In
a hemorrhage scenario, the preload control maintained the greatest safety margin
against LV suction. PLVED for the preload controller was 4.9 mmHg, compared with
0.4 mmHg for the pulsatility controller and 0.2 mmHg for the constant speed mode.
This was associated with an adequate mean arterial pressure (MAP) of 84 mmHg. In
transition to low LVC, [Formula: see text] for preload control remained constant
at 5.22 L/min with a PLVED of 8.0 mmHg. With regards to pulsatility control,
[Formula: see text] fell to the nonviable level of 2.4 L/min with an associated
PLVED of 16 mmHg and a MAP of 55 mmHg. Consequently, pulsatility control was
deemed inferior to constant speed mode with a PLVED of 11 mmHg and a [Formula:
see text] of 5.13 L/min in low LVC scenario. We conclude that pulsatility control
imposes a danger to the patient in the severely reduced LVC scenario, which can
be overcome by using a preload-based Starling-like control approach.
PMID- 25849980
TI - LPA signaling initiates schizophrenia-like brain and behavioral changes in a
mouse model of prenatal brain hemorrhage.
AB - Genetic, environmental and neurodevelopmental factors are thought to underlie the
onset of neuropsychiatric disorders such as schizophrenia. How these risk factors
collectively contribute to pathology is unclear. Here, we present a mouse model
of prenatal intracerebral hemorrhage--an identified risk factor for schizophrenia
-using a serum-exposure paradigm. This model exhibits behavioral, neurochemical
and schizophrenia-related gene expression alterations in adult females.
Behavioral alterations in amphetamine-induced locomotion, prepulse inhibition,
thigmotaxis and social interaction--in addition to increases in tyrosine
hydroxylase-positive dopaminergic cells in the substantia nigra and ventral
tegmental area and decreases in parvalbumin-positive cells in the prefrontal
cortex--were induced upon prenatal serum exposure. Lysophosphatidic acid (LPA), a
lipid component of serum, was identified as a key molecular initiator of
schizophrenia-like sequelae induced by serum. Prenatal exposure to LPA alone
phenocopied many of the schizophrenia-like alterations seen in the serum model,
whereas pretreatment with an antagonist against the LPA receptor subtype LPA1
prevented many of the behavioral and neurochemical alterations. In addition, both
prenatal serum and LPA exposure altered the expression of many genes and pathways
related to schizophrenia, including the expression of Grin2b, Slc17a7 and Grid1.
These findings demonstrate that aberrant LPA receptor signaling associated with
fetal brain hemorrhage may contribute to the development of some neuropsychiatric
disorders.
PMID- 25849981
TI - The role of glucocorticoid receptor-dependent activity in the amygdala central
nucleus and reversibility of early-life stress programmed behavior.
AB - Early-life stress (ELS) leads to sustained changes in gene expression and
behavior, increasing the likelihood of developing a psychiatric disorder in
adulthood. The neurobiological basis for the later-in-life psychopathology is
relatively unknown. The current study used a mouse model of ELS, achieved by
daily maternal separations during the first 2 weeks of postnatal life, to test
the role of amygdalar glucocorticoid receptor (GR) function in mediating the
persistent increase in risk-taking behaviors. ELS produced a decrease in GR mRNA
in the brain, with a notable reduction in the amygdala that was associated with
sustained alterations in anxiety, fear and sociability-like behaviors. Lentiviral
mediated restoration of the GR mRNA deficit, specifically within the adult
central nucleus of the amygdala (CeA), reversed the enduring changes in anxiety
and social behavior after ELS. These results provide evidence of lasting changes
in CeA GR neural circuitry following ELS and suggest a mechanistic role for GR
regulated processes in the CeA in mediating the lifelong maladaptive behaviors of
ELS. We demonstrate that the long-lasting behavioral effects of ELS are
reversible later in life and implicate the involvement of CeA GR-dependent
activity in the sustained dysregulation of emotion following ELS.
PMID- 25849982
TI - Allergic fetal priming leads to developmental, behavioral and neurobiological
changes in mice.
AB - The state of the mother's immune system during pregnancy has an important role in
fetal development and disruptions in the balance of this system are associated
with a range of neurologic, neuropsychiatric and neurodevelopmental disorders.
Epidemiological and clinical reports reveal various clues that suggest a possible
association between developmental neuropsychiatric disorders and family history
of immune system dysfunction. Over the past three decades, analogous increases
have been reported in both the incidence of neurodevelopmental disorders and
immune-related disorders, particularly allergy and asthma, raising the question
of whether allergic asthma and characteristics of various neurodevelopmental
disorders share common causal links. We used a mouse model of maternal allergic
asthma to test this novel hypothesis that early fetal priming with an allergenic
exposure during gestation produces behavioral deficits in offspring. Mothers were
primed with an exposure to ovalbumin (OVA) before pregnancy, then exposed to
either aerosolized OVA or vehicle during gestation. Both male and female mice
born to mothers exposed to aerosolized OVA during gestation exhibited altered
developmental trajectories in weight and length, decreased sociability and
increased marble-burying behavior. Moreover, offspring of OVA-exposed mothers
were observed to have increased serotonin transporter protein levels in the
cortex. These data demonstrate that behavioral and neurobiological effects can be
elicited following early fetal priming with maternal allergic asthma and provide
support that maternal allergic asthma may, in some cases, be a contributing
factor to neurodevelopmental disorders.
PMID- 25849983
TI - D-cycloserine to enhance extinction of cue-elicited craving for alcohol: a
translational approach.
AB - Cue-elicited craving for alcohol is well established but extinction-based
treatment to extinguish this response has generated only modest positive outcomes
in clinical trials. Basic and clinical research suggests that D-cycloserine (DCS)
enhances extinction to fear cues under certain conditions. However, it remains
unclear whether DCS would also accelerate extinction of cue-elicited craving for
alcohol. The goal of the current study was to examine whether, compared with
placebo (PBO), DCS enhanced extinction of cue-elicited craving among treatment
seeking individuals with alcohol use disorders (AUDs). Participants were
administered DCS (50 mg) or PBO 1 h before an alcohol extinction paradigm in a
simulated bar environment on two occasions. The extinction procedures occurred 1
week apart and were fully integrated into outpatient treatment. Subjective
craving for alcohol was the primary variable of interest. Follow-up cue
reactivity sessions were conducted 1 week and 3 weeks later to ascertain
persisting DCS effects. Drinking outcomes and tolerability were also examined.
DCS was associated with augmented reductions in alcohol craving to alcohol cues
during the first extinction session and these effects persisted through all
subsequent sessions, suggesting facilitation of extinction. Participants in the
DCS condition reported significant short-term reductions in drinking, although
these did not persist to follow-up, and found the medication highly tolerable.
These findings provide evidence that DCS enhances extinction of cue-elicited
craving for alcohol in individuals with AUDs in the context of outpatient
treatment. The potential clinical utility of DCS is discussed, including
methodological considerations and context-dependent learning.
PMID- 25849984
TI - Maternal depression is associated with DNA methylation changes in cord blood T
lymphocytes and adult hippocampi.
AB - Depression affects 10-15% of pregnant women and has been associated with preterm
delivery and later developmental, behavioural and learning disabilities. We
tested the hypothesis that maternal depression is associated with DNA methylation
alterations in maternal T lymphocytes, neonatal cord blood T lymphocytes and
adult offspring hippocampi. Genome-wide DNA methylation of CD3+ T lymphocytes
isolated from 38 antepartum maternal and 44 neonatal cord blood samples were
analyzed using Illumina Methylation 450 K microarrays. Previously obtained
methylation data sets using methylated DNA immunoprecipitation and array
hybridization of 62 postmortem hippocampal samples of adult males were re
analyzed to test associations with history of maternal depression. We found 145
(false discovery rate (FDR) q<0.05) and 2520 (FDR q<0.1) differentially
methylated CG-sites in cord blood T lymphocytes of neonates from the maternal
depression group as compared with the control group. However, no significant DNA
methylation differences were detected in the antepartum maternal T lymphocytes of
our preliminary data set. We also detected 294 differentially methylated probes
(FDR q<0.1) in hippocampal samples associated with history of maternal
depression. We observed a significant overlap (P=0.002) of 33 genes with changes
in DNA methylation in T lymphocytes of neonates and brains of adult offspring.
Many of these genes are involved in immune system functions. Our results show
that DNA methylation changes in offspring associated with maternal depression are
detectable at birth in the immune system and persist to adulthood in the brain.
This is consistent with the hypothesis that system-wide epigenetic changes are
involved in life-long responses to maternal depression in the offspring.
PMID- 25849985
TI - Synaptic vesicle release regulates myelin sheath number of individual
oligodendrocytes in vivo.
AB - The myelination of axons by oligodendrocytes markedly affects CNS function, but
how this is regulated by neuronal activity in vivo is not known. We found that
blocking synaptic vesicle release impaired CNS myelination by reducing the number
of myelin sheaths made by individual oligodendrocytes during their short period
of formation. We also found that stimulating neuronal activity increased myelin
sheath formation by individual oligodendrocytes. These data indicate that
neuronal activity regulates the myelinating capacity of single oligodendrocytes.
PMID- 25849986
TI - Regulation of chromatin accessibility and Zic binding at enhancers in the
developing cerebellum.
AB - To identify chromatin mechanisms of neuronal differentiation, we characterized
chromatin accessibility and gene expression in cerebellar granule neurons (CGNs)
of the developing mouse. We used DNase-seq to map accessibility of cis-regulatory
elements and RNA-seq to profile transcript abundance across postnatal stages of
neuronal differentiation in vivo and in culture. We observed thousands of
chromatin accessibility changes as CGNs differentiated, and verified, using
H3K27ac ChIP-seq, reporter gene assays and CRISPR-mediated activation, that many
of these regions function as neuronal enhancers. Motif discovery in
differentially accessible chromatin regions suggested a previously unknown role
for the Zic family of transcription factors in CGN maturation. We confirmed the
association of Zic with these elements by ChIP-seq and found, using knockdown,
that Zic1 and Zic2 are required for coordinating mature neuronal gene expression
patterns. Together, our data reveal chromatin dynamics at thousands of gene
regulatory elements that facilitate the gene expression patterns necessary for
neuronal differentiation and function.
PMID- 25849987
TI - Neuronal activity biases axon selection for myelination in vivo.
AB - An essential feature of vertebrate neural development is ensheathment of axons
with myelin, an insulating membrane formed by oligodendrocytes. Not all axons are
myelinated, but mechanisms directing myelination of specific axons are unknown.
Using zebrafish, we found that activity-dependent secretion stabilized myelin
sheath formation on select axons. When VAMP2-dependent exocytosis was silenced in
single axons, oligodendrocytes preferentially ensheathed neighboring axons.
Nascent sheaths formed on silenced axons were shorter in length, but when
activity of neighboring axons was also suppressed, inhibition of sheath growth
was relieved. Using in vivo time-lapse microscopy, we found that only 25% of
oligodendrocyte processes that initiated axon wrapping were stabilized during
normal development and that initiation did not require activity. Instead,
oligodendrocyte processes wrapping silenced axons retracted more frequently. We
propose that axon selection for myelination results from excessive and
indiscriminate initiation of wrapping followed by refinement that is biased by
activity-dependent secretion from axons.
PMID- 25849988
TI - Medial prefrontal cortical activity reflects dynamic re-evaluation during
voluntary persistence.
AB - Deciding how long to keep waiting for future rewards is a nontrivial problem,
especially when the timing of rewards is uncertain. We carried out an experiment
in which human decision makers waited for rewards in two environments in which
reward-timing statistics favored either a greater or lesser degree of behavioral
persistence. We found that decision makers adaptively calibrated their level of
persistence for each environment. Functional neuroimaging revealed signals that
evolved differently during physically identical delays in the two environments,
consistent with a dynamic and context-sensitive reappraisal of subjective value.
This effect was observed in a region of ventromedial prefrontal cortex that is
sensitive to subjective value in other contexts, demonstrating continuity between
valuation mechanisms involved in discrete choice and in temporally extended
decisions analogous to foraging. Our findings support a model in which voluntary
persistence emerges from dynamic cost/benefit evaluation rather than from a
control process that overrides valuation mechanisms.
PMID- 25849989
TI - Learning-induced autonomy of sensorimotor systems.
AB - Distributed networks of brain areas interact with one another in a time-varying
fashion to enable complex cognitive and sensorimotor functions. Here we used new
network-analysis algorithms to test the recruitment and integration of large
scale functional neural circuitry during learning. Using functional magnetic
resonance imaging data acquired from healthy human participants, we investigated
changes in the architecture of functional connectivity patterns that promote
learning from initial training through mastery of a simple motor skill. Our
results show that learning induces an autonomy of sensorimotor systems and that
the release of cognitive control hubs in frontal and cingulate cortices predicts
individual differences in the rate of learning on other days of practice. Our
general statistical approach is applicable across other cognitive domains and
provides a key to understanding time-resolved interactions between distributed
neural circuits that enable task performance.
PMID- 25849991
TI - Composition, variation, expression and evolution of low-molecular-weight glutenin
subunit genes in Triticum urartu.
AB - BACKGROUND: Wheat (AABBDD, 2n = 6x = 42) is a major dietary component for many
populations across the world. Bread-making quality of wheat is mainly determined
by glutenin subunits, but it remains challenging to elucidate the composition and
variation of low-molecular-weight glutenin subunits (LMW-GS) genes, the major
components for glutenin subunits in hexaploid wheat. This problem, however, can
be greatly simplified by characterizing the LMW-GS genes in Triticum urartu, the
A-genome donor of hexaploid wheat. In the present study, we exploited the high
throughput molecular marker system, gene cloning, proteomic methods and molecular
evolutionary genetic analysis to reveal the composition, variation, expression
and evolution of LMW-GS genes in a T. urartu population from the Fertile Crescent
region. RESULTS: Eight LMW-GS genes, including four m-type, one s-type and three
i-type, were characterized in the T. urartu population. Six or seven genes, the
highest number at the Glu-A3 locus, were detected in each accession. Three i-type
genes, each containing more than six allelic variants, were tightly linked
because of their co-segregation in every accession. Only 2-3 allelic variants
were detected for each m- and s-type gene. The m-type gene, TuA3-385, for which
homologs were previously characterized only at Glu-D3 locus in common wheat and
Aegilops tauschii, was detected at Glu-A3 locus in T. urartu. TuA3-460 was the
first s-type gene identified at Glu-A3 locus. Proteomic analysis showed 1-4
genes, mainly i-type, expressed in individual accessions. About 62% accessions
had three active i-type genes, rather than one or two in common wheat.
Southeastern Turkey might be the center of origin and diversity for T. urartu due
to its abundance of LMW-GS genes/genotypes. Phylogenetic reconstruction
demonstrated that the characterized T. urartu might be the direct donor of the
Glu-A3 locus in common wheat varieties. CONCLUSIONS: Compared with the Glu-A3
locus in common wheat, a large number of highly diverse LMW-GS genes and active
genes were characterized in T. urartu, demonstrating that this progenitor might
provide valuable genetic resources for LMW-GS genes to improve the quality of
common wheat. The phylogenetic analysis provided molecular evidence and confirmed
that T. urartu was the A-genome donor of hexaploid wheat.
PMID- 25849992
TI - Men's facial width-to-height ratio predicts aggression: a meta-analysis.
AB - Recent research has identified men's facial width-to-height ratio (fWHR) as a
reliable predictor of aggressive tendencies and behavior. Other research,
however, has failed to replicate the fWHR-aggression relationship and has
questioned whether previous findings are robust. In the current paper, we
synthesize existing work by conducting a meta-analysis to estimate whether and
how fWHR predicts aggression. Our results indicate a small, but significant,
positive relationship between men's fWHR and aggression.
PMID- 25849990
TI - Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to
myeloproliferative neoplasms.
AB - Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic
mutations in JAK2, CALR or MPL, but the contribution of inherited factors is
poorly characterized. Using a three-stage genome-wide association study of 3,437
MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance
in JAK2(V617F)-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 * 10(-10))
and rs2201862 (MECOM; meta-analysis P=1.96 * 10(-9)). Two additional SNPs,
rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when
including JAK2(V617F)-positive cases. rs9376092 has a stronger effect in
JAK2(V617F)-negative cases with CALR and/or MPL mutations (Breslow-Day P=4.5 *
10(-7)), whereas in JAK2(V617F)-positive cases rs9376092 associates with
essential thrombocythemia (ET) rather than polycythemia vera (allelic chi(2)
P=7.3 * 10(-7)). Reduced MYB expression, previously linked to development of an
ET-like disease in model systems, associates with rs9376092 in normal myeloid
cells. These findings demonstrate that multiple germline variants predispose to
MPN and link constitutional differences in MYB expression to disease phenotype.
PMID- 25849994
TI - Effects of composition and processing variables on the oxidative stability of
protein-based and oil-in-water food emulsions.
AB - Because many common foods are emulsions (mayonnaise, coffee creamers, salad
dressing, etc.), a better understanding of lipid oxidation mechanisms in these
systems is crucial for the formulation, production, and storage of the relevant
consumer products. A research body has focused on the microstructural and
oxidative stability of protein-stabilized oil-in-water emulsions that are
structurally similar to innovative products that have been recently developed by
the food industry (e.g., non-dairy creams, vegetable fat spreads, etc.) This
review presents recent findings about the factors that determine the development
of lipid oxidation in emulsions where proteins constitute the stabilizing
interface. Emphasis is given to "endogenous" factors, such as those of
compositional (e.g., protein/lipid phases, pH, presence of transition metals) or
processing (e.g., temperature, droplet size) nature. Improved knowledge of the
conditions that favor the oxidative protection of protein in emulsions can lead
to their optimized use as food ingredients and thereby improve the organoleptic
and nutritional value of the related products.
PMID- 25849993
TI - Autophagy protects monocytes from Wolbachia heat shock protein 60-induced
apoptosis and senescence.
AB - Monocyte dysfunction by filarial antigens has been a major mechanism underlying
immune evasion following hyporesponsiveness during patent lymphatic filariasis.
Recent studies have initiated a paradigm shift to comprehend the immunological
interactions of Wolbachia and its antigens in inflammation, apoptosis, lymphocyte
anergy, etc. Here we showed that recombinant Wolbachia heat shock protein 60
(rWmhsp60) interacts with TLR-4 and induces apoptosis in monocytes of endemic
normal but not in chronic patients. Higher levels of reactive oxygen species
(ROS) induced after TLR-4 stimulation resulted in loss of mitochondrial membrane
potential and caspase cascade activation, which are the plausible reason for
apoptosis. Furthermore, release in ROS owing to TLR-4 signaling resulted in the
activation of NF-kappaB p65 nuclear translocation which leads to inflammation and
apoptosis via TNF receptor pathway following the increase in IL-6 and TNF-alpha
level. Here for the first time, we report that in addition to apoptosis, rWmhsp60
antigen in filarial pathogenesis also induces molecular senescence in monocytes.
Targeting TLR-4, therefore, presents a promising candidate for treating rWmhsp60
induced apoptosis and senescence. Strikingly, induction of autophagy by rapamycin
detains TLR-4 in late endosomes and subverts TLR-4-rWmhsp60 interaction, thus
protecting TLR-4-mediated apoptosis and senescence. Furthermore, rapamycin
induced monocytes were unresponsive to rWmhsp60, and activated lymphocytes
following PHA stimulation. This study demonstrates that autophagy mediates the
degradation of TLR-4 signaling and protects monocytes from rWmhsp60 induced
apoptosis and senescence.
PMID- 25849995
TI - Psychometric properties of the Persian version of Death Depression Scale among
nurses.
AB - This study is an attempt to investigate validity and reliability of the Persian
version of Death Depression Scale among male and female nurses at Jundishapur
University of Medical Science and 2 private hospitals in Ahvaz, Iran, who were
selected by a convenience sampling method after obtaining informed consent. They
completed the Death Depression Scale-Revised (DDS-R), Death Anxiety Scale, Death
Obsession Scale, as well as Short-Form of Beck Depression Questionnaire (BDI-13).
The results of exploratory factor analysis on DDS-R identified 3 factors.
Cronbach's alpha coefficient was 0.93 for the entire measure (19 items), with
alphas ranging from .80 to .94 for the individual factors. Indices of concurrent
validity for this scale with Death Anxiety, Death Obsession Scales, and BDI-13
were all significant (p < 0.001). Given the validity and reliability of the DDS
R, this scale can be used in clinical settings and research studies.
PMID- 25849996
TI - Dynamic interplay of spectrosome and centrosome organelles in asymmetric stem
cell divisions.
AB - Stem cells have remarkable self-renewal ability and differentiation potency,
which are critical for tissue repair and tissue homeostasis. Recently it has been
found, in many systems (e.g. gut, neurons, and hematopoietic stem cells), that
the self-renewal and differentiation balance is maintained when the stem cells
divide asymmetrically. Drosophila male germline stem cells (GSCs), one of the
best characterized model systems with well-defined stem cell niches, were
reported to divide asymmetrically, where centrosome plays an important role.
Utilizing time-lapse live cell imaging, customized tracking, and image processing
programs, we found that most acentrosomal GSCs have the spectrosomes reposition
from the basal end (wild type) to the apical end close to hub-GSC interface
(acentrosomal GSCs). In addition, these apically positioned spectrosomes were
mostly stationary while the basally positioned spectrosomes were mobile. For
acentrosomal GSCs, their mitotic spindles were still highly oriented and divided
asymmetrically with longer mitosis duration, resulting in asymmetric divisions.
Moreover, when the spectrosome was knocked out, the centrosomes velocity
decreased and centrosomes located closer to hub-GSC interface. We propose that in
male GSCs, the spectrosome recruited to the apical end plays a complimentary role
in ensuring proper spindle orientation when centrosome function is compromised.
PMID- 25849997
TI - Preparation of acetylsalicylic acid-acylated chitosan as a novel polymeric drug
for drug controlled release.
AB - The acetylsalicylic acid-acylated chitosan (ASACTS) with high degree of
substitution (DS) was successfully synthesized, and characterized with FTIR, (1)H
NMR and elemental analysis methods. The optimum synthesis conditions were
obtained which gave the highest DS (about 60%) for ASACTS. Its drug release
experiments were carried out in simulated gastric and intestine fluids. The
results show that the drugs in the form of acetylsalicylic acid (ASA) and
salicylic acid (SA) were released in a controlled manner from ASACTS only in
simulated gastric fluid. The release profile can be best fitted with logistic and
Weibull model. The research results reveal that ASACTS can be a potential
polymeric drug for the controlled release of ASA and SA in the targeted gastric
environment.
PMID- 25849998
TI - Interaction of a green ester-bonded gemini surfactant with xanthine oxidase:
Biophysical perspective.
AB - A multi technique approach was utilized to explore the interaction between a
novel green gemini surfactant, ethane-1,2-diyl bis(N,N-dimethyl-N
tetradecylammoniumacetoxy) dichloride (14-E2-14), with bovine milk xanthine
oxidase (XO). Tensiometric, spectroscopic, microscopic and molecular modeling
results demonstrate significant interaction and structural change of native
xanthine oxidase upon 14-E2-14 combination. The results obtained in this study
may be beneficial for scientists to calibrate conformation of the enzyme by novel
biodegradable/green microstructures; consequently, it would likely add new
impetus in understanding the treatment modes of various diseases like gout,
hyperuricemia, liver and brain necrosis. Moreover, the 14-E2-14-XO interaction
assists to unfurl new routes in the designing/selection of green-surfactant
protein mixtures widely used in food processing, cosmetics, and pharmaceutical
industries.
PMID- 25849999
TI - Fabrication of 3D porous silk scaffolds by particulate (salt/sucrose) leaching
for bone tissue reconstruction.
AB - Silk fibroin is a biomaterial being actively studied in the field of bone tissue
engineering. In this study, we aimed to select the best strategy for bone
reconstruction on scaffolds by changing various conditions. We compared the
characteristics of each scaffold via structural analysis using scanning electron
microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), the swelling
ratio, water uptake, porosity, compressive strength, cell infiltration and cell
viability (CCK-8). The scaffolds had high porosity with good inter pore
connectivity and showed high compressive strength and modulus. In addition, to
confirm bone reconstruction, animal studies were conducted in which samples were
implanted in rat calvaria and investigated by micro-CT scans. In conclusion, the
presented study indicates that using sucrose produces scaffolds showing better
pore interconnectivity and cell infiltration than scaffolds made by using a salt
process. In addition, in vivo experiments showed that hydroxyapatite accelerates
bone reconstruction on implanted scaffolds. Accordingly, our scaffold will be
expected to have a useful application in bone reconstruction.
PMID- 25850000
TI - Development and mechanism investigation of a new piperlongumine derivative as a
potent anti-inflammatory agent.
AB - Inflammation, especially chronic inflammation, is directly involvement in the
pathogenesis of many diseases including cancer. An effective approach for
managing inflammation is to employ chemicals to block activation of nuclear
factor-kappaB (NF-kappaB), a key regulator for inflammatory processes.
Piperlongumine (piplartine, PL), an electrophilic molecule isolated from Piper
longum L., possesses excellent anti-cancer and anti-inflammatory properties. In
this study, a new PL analogue (PL-0N) was designed by replacing nitrogen atom of
lactam in PL with carbon atom to increase its electrophilicity and thus anti
inflammatory activity. It was found that PL-0N is more potent than the parent
compound in suppressing lipopolysaccharide (LPS)-induced secretion of nitric
oxide and prostaglandin E2 as well as expression of inducible nitric oxide
synthase and cyclooxygenase-2 in RAW264.7 macrophages. Mechanistic investigation
implies that PL-0N exerts anti-inflammatory activity through inhibition of LPS
induced NF-kappaB transduction pathway, down-regulation of LPS-induced MAPKs
activation and impairment of proteasomal activity, but also enhancement of LPS
induced autophagy; the inhibition of NF-kappaB by PL-0N is achieved at various
stages by: (i) preventing phosphorylation of IKKalpha/beta, (ii) stabilizing the
suppressor protein IkappaBalpha, (iii) interfering with the nuclear translocation
of NF-kappaB, and (iv) inhibiting the DNA-binding of NF-kappaB. These data
indicate that nitrogen-atom-lacking pattern is a successful strategy to improve
anti-inflammatory property of PL, and that the novel molecule, PL-0N may be
served as a promising lead for developing natural product-directed anti
inflammatory agents.
PMID- 25850001
TI - Continuing treatment with Salvia miltiorrhiza injection attenuates myocardial
fibrosis in chronic iron-overloaded mice.
AB - Iron overload cardiomyopathy results from iron accumulation in the myocardium
that is closely linked to iron-mediated myocardial fibrosis. Salvia miltiorrhiza
(SM, also known as Danshen), a traditional Chinese medicinal herb, has been
widely used for hundreds of years to treat cardiovascular diseases. Here, we
investigated the effect and potential mechanism of SM on myocardial fibrosis
induced by chronic iron overload (CIO) in mice. Kunming male mice (8 weeks old)
were randomized to six groups of 10 animals each: control (CONT), CIO, low-dose
SM (L-SM), high-dose SM (H-SM), verapamil (VRP) and deferoxamine (DFO) groups.
Normal saline was injected in the CONT group. Mice in the other five groups were
treated with iron dextran at 50 mg/kg per day intraperitoneally for 7 weeks, and
those in the latter four groups also received corresponding daily treatments,
including 3 g/kg or 6 g/kg of SM, 100 mg/kg of VRP, or 100 mg/kg of DFO. The iron
deposition was estimated histologically using Prussian blue staining. Myocardial
fibrosis was determined by Masson's trichrome staining and hydroxyproline (Hyp)
quantitative assay. Superoxide dismutase (SOD) activity, malondialdehyde (MDA)
content and protein expression levels of type I collagen (COL I), type I collagen
(COL III), transforming growth factor-beta1 (TGF-beta1) and matrix
metalloproteinase-9 (MMP-9) were analyzed to investigate the mechanisms
underlying the effects of SM against iron-overloaded fibrosis. Treatment of
chronic iron-overloaded mice with SM dose-dependently reduced iron deposition
levels, fibrotic area percentage, Hyp content, expression levels of COL I and COL
III, as well as upregulated the expression of TGF- beta1 and MMP-9 proteins in
the heart. Moreover, SM treatment decreased MDA content and increased SOD
activity. In conclusion, SM exerted activities against cardiac fibrosis induced
by CIO, which may be attributed to its inhibition of iron deposition, as well as
collagen metabolism and oxidative stress.
PMID- 25850002
TI - Mechanistic and Structural Analysis of a Drosophila melanogaster Enzyme,
Arylalkylamine N-Acetyltransferase Like 7, an Enzyme That Catalyzes the Formation
of N-Acetylarylalkylamides and N-Acetylhistamine.
AB - Arylalkylamine N-acetyltransferase like 7 (AANATL7) catalyzes the formation of N
acetylarylalkylamides and N-acetylhistamine from acetyl-CoA and the corresponding
amine substrate. AANATL7 is a member of the GNAT superfamily of >10000 GCN5
related N-acetyltransferases, many members being linked to important roles in
both human metabolism and disease. Drosophila melanogaster utilizes the N
acetylation of biogenic amines for the inactivation of neurotransmitters, the
biosynthesis of melatonin, and the sclerotization of the cuticle. We have
expressed and purified D. melanogaster AANATL7 in Escherichia coli and used the
purified enzyme to define the substrate specificity for acyl-CoA and amine
substrates. Information about the substrate specificity provides insight into the
potential contribution made by AANATL7 to fatty acid amide biosynthesis because
D. melanogaster has emerged as an important model system contributing to our
understanding of fatty acid amide metabolism. Characterization of the kinetic
mechanism of AANATL7 identified an ordered sequential mechanism, with acetyl-CoA
binding first followed by histamine to generate an AANATL7.acetyl-CoA.histamine
ternary complex prior to catalysis. Successive pH-activity profiling and site
directed mutagenesis experiments identified two ionizable groups: one with a pKa
of 7.1 that is assigned to Glu-26 as a general base and a second pKa of 9.5 that
is assigned to the protonation of the thiolate of the coenzyme A product. Using
the data generated herein, we propose a chemical mechanism for AANATL7 and define
functions for other important amino acid residues involved in substrate binding
and regulation of catalysis.
PMID- 25850004
TI - Advantages and limitations of the use of optogenetic approach in studying fast
scale spike encoding.
AB - Understanding single-neuron computations and encoding performed by spike
generation mechanisms of cortical neurons is one of the central challenges for
cell electrophysiology and computational neuroscience. An established paradigm to
study spike encoding in controlled conditions in vitro uses intracellular
injection of a mixture of signals with fluctuating currents that mimic in vivo
like background activity. However this technique has two serious limitations: it
uses current injection, while synaptic activation leads to changes of
conductance, and current injection is technically most feasible in the soma,
while the vast majority of synaptic inputs are located on the dendrites. Recent
progress in optogenetics provides an opportunity to circumvent these limitations.
Transgenic expression of light-activated ionic channels, such as
Channelrhodopsin2 (ChR2), allows induction of controlled conductance changes even
in thin distant dendrites. Here we show that photostimulation provides a useful
extension of the tools to study neuronal encoding, but it has its own
limitations. Optically induced fluctuating currents have a low cutoff (~70 Hz),
thus limiting the dynamic range of frequency response of cortical neurons. This
leads to severe underestimation of the ability of neurons to phase-lock their
firing to high frequency components of the input. This limitation could be worked
around by using short (2 ms) light stimuli which produce membrane potential
responses resembling EPSPs by their fast onset and prolonged decay kinetics. We
show that combining application of short light stimuli to different parts of
dendritic tree for mimicking distant EPSCs with somatic injection of fluctuating
current that mimics fluctuations of membrane potential in vivo, allowed us to
study fast encoding of artificial EPSPs photoinduced at different distances from
the soma. We conclude that dendritic photostimulation of ChR2 with short light
pulses provides a powerful tool to investigate population encoding of simulated
synaptic potentials generated in dendrites at different distances from the soma.
PMID- 25850005
TI - Apparent pH sensitivity of solution-gated graphene transistors.
AB - Solution-gated graphene transistors were developed recently for use in pH sensor
applications. The device operation is understood to rely on the capability of
hydronium and hydroxide ions in solution to change the electrical properties of
graphene. However, hydronium and hydroxide ions are accompanied by other ionic
species in a typical acidic or basic solution and, therefore, the roles of these
other ionic species must be also considered to fully understand the pH response
of such devices. Using series of pH buffer solutions designed carefully, we
verified that the magnitude and even the direction of pH-dependent Dirac voltage
(VDirac) shift (the typical pH sensing indicator) depend strongly on the
concentration and composition of the buffers used. The results indicate that the
interpretation of the apparent pH-dependent VDirac response of a solution-gated
graphene transistor must include the contributions of the additional ions in the
solution.
PMID- 25850006
TI - Serum fibroblast growth factor 21 levels is associated with lower extremity
atherosclerotic disease in Chinese female diabetic patients.
AB - BACKGROUND: Fibroblast growth factor 21 (FGF21) is an emerging metabolic
regulator associated with glucose and lipid metabolism, and it is still unclear
whether FGF21 is related to atherosclerosis. Here, we explored the potential link
between FGF21 and lower extremity atherosclerotic disease (LEAD) in type 2
diabetic patients. METHODS: A cross-sectional study was conducted on 504 type 2
diabetic patients (283 men, 221 women). LEAD was defined by Ankle-brachial index
(ABI) <0.9 and lower extremity arterial plaque evaluated by color Doppler
ultrasound. Serum FGF21 concentrations were quantified by a sandwich enzyme
linked immunosorbent assay. RESULTS: The total FGF21 levels of male and female
patients had no significant differenence ((299.14(177.31-534.49) vs 362.50(214.01
578.73), P=0.516). Serum FGF21 levels in LEAD group were significantly higher
than non-LEAD group in females (385.34(243.89-661.54) vs 313.13(156.38-485.79),
P=0.006), while not in male patients (295.52(177.09-549.64) vs 342.09 (198.70
549.87), P=0.613). In diabetic women, subjects with LEAD had significantly higher
serum FGF21 regardless of non-alcoholic fatty liver disease (NAFLD) (P < 0.05).
And serum FGF21 levels were positively correlated with waist circumference and
systolic blood pressure after adjusted for age and BMI (r=0.198, P=0.004;
r=0.152, P=0.027; respectively). Moreover, FGF21 was independently tied to
femoral intima-media thickness (FIMT) (beta=0.208, P=0.031). After adjusted for
other LEAD risk factors, FGF21 was demonstrated to be an independent risk factor
for LEAD in type 2 diabetic women (OR, 1.106; 95%CI 1.008-1.223; P=0.028). In
addition, FGF21 was negatively correlated with estradiol in premenopausal
diabetic women (r=-0.368, P=0.009). After adjusted for estradiol, serum FGF21
levels were still positively associated with FIMT in premenopausal diabetic women
(r=0.381, P=0.007). In diabetic men, serum FGF21 levels were correlated with
triglyceride and C-reactive protein even after adjusted for age and BMI (r=0.204,
P=0.001; r=0.312, P < 0.001; respectively). However, serum FGF21 was not an
independent impact factor for LEAD in men (P > 0.05). CONCLUSIONS: Serum FGF21
level independently and positively links LEAD in Chinese women with type 2
diabetes. The gender difference may be due to different estrogen levels.
PMID- 25850007
TI - Powerful regulatory systems and post-transcriptional gene silencing resist
increases in cellulose content in cell walls of barley.
AB - BACKGROUND: The ability to increase cellulose content and improve the stem
strength of cereals could have beneficial applications in stem lodging and
producing crops with higher cellulose content for biofuel feedstocks. Here, such
potential is explored in the commercially important crop barley through the
manipulation of cellulose synthase genes (CesA). RESULTS: Barley plants
transformed with primary cell wall (PCW) and secondary cell wall (SCW) barley
cellulose synthase (HvCesA) cDNAs driven by the CaMV 35S promoter, were analysed
for growth and morphology, transcript levels, cellulose content, stem strength,
tissue morphology and crystalline cellulose distribution. Transcript levels of
the PCW HvCesA transgenes were much lower than expected and silencing of both the
endogenous CesA genes and introduced transgenes was often observed. These plants
showed no aberrant phenotypes. Although attempts to over-express the SCW HvCesA
genes also resulted in silencing of the transgenes and endogenous SCW HvCesA
genes, aberrant phenotypes were sometimes observed. These included brittle nodes
and, with the 35S:HvCesA4 construct, a more severe dwarfing phenotype, where
xylem cells were irregular in shape and partially collapsed. Reductions in
cellulose content were also observed in the dwarf plants and transmission
electron microscopy showed a significant decrease in cell wall thickness.
However, there were no increases in overall crystalline cellulose content or stem
strength in the CesA over-expression transgenic plants, despite the use of a
powerful constitutive promoter. CONCLUSIONS: The results indicate that the
cellulose biosynthetic pathway is tightly regulated, that individual CesA
proteins may play different roles in the synthase complex, and that the
sensitivity to CesA gene manipulation observed here suggests that in planta
engineering of cellulose levels is likely to require more sophisticated
strategies.
PMID- 25850009
TI - Hepatitis: Tightening the grip on clearing HCV infection.
PMID- 25850008
TI - Dysphagia: current reality and scope of the problem.
AB - Dysphagia is a symptom of swallowing dysfunction that occurs between the mouth
and the stomach. Although oropharyngeal dysphagia is a highly prevalent condition
(occurring in up to 50% of elderly people and 50% of patients with neurological
conditions) and is associated with aspiration, severe nutritional and respiratory
complications and even death, most patients are not diagnosed and do not receive
any treatment. By contrast, oesophageal dysphagia is less prevalent and less
severe, but with better recognized symptoms caused by diseases affecting the
enteric nervous system and/or oesophageal muscular layers. Recognition of the
clinical relevance and complications of oesophageal and oropharyngeal dysphagia
is growing among health-care professionals in many fields. In addition, the
emergence of new methods to screen and assess swallow function at both the
oropharynx and oesophagus, and marked advances in understanding the
pathophysiology of these conditions, is paving the way for a new era of intensive
research and active therapeutic strategies for affected patients. Indeed, a
unified field of deglutology is developing, with new professional profiles to
cover the needs of all patients with dysphagia in a nonfragmented way.
PMID- 25850010
TI - Thinprep plus Papanicolaou stain method is more sensitive than cytospin-coupled
Wright Giems stain method in cerebrospinal fluid cytology for diagnosis of
leptomeningeal metastasis from solid tumors.
AB - BACKGROUND: The present study was designed to determine whether the Thinprep plus
Papanicolaou stain (Thinprep) method is more sensitive than the Cytospin-coupled
Wright-Giemsa (WG) stain (Cytospin) method in diagnosis of leptomeningeal
metastasis (LM) from malignant solid tumors in cerebrospinal fluid (CSF). We also
explored if the Thinprep method could be used in the differential diagnosis of
the type of primary tumor cells based on the morphology of tumor cells in CSF
samples. METHODS: The morphological features of tumor cells in fresh CSF samples
were analyzed using both methods. The tumor cell detection rates were compared
between the two methods. RESULTS: Using the Thinprep method, we found that each
type of tumor cells in the CSF samples had specific identifiable morphological
features linked to their primary cancer origins, such as adenocarcinomas
originated from the lungs, breast, and stomach, and lung squamous cell
carcinomas, small cell lung cancer, large-cell neuroendocrine lung cancer,
hepatocellular carcinoma, and malignant melanoma. In a retrospective study with
88 LM patients, cancer cells were detected in 80 out of the 88 CSF samples. In
the comparative study with 45 LM patients, the initial detection rate of the
Thinprep method was significantly higher than that of the Cytospin method (73.3%
vs. 57.8%, P<0.01). The cell morphology was better preserved and subcellular
structures were clearer using the Thinprep method, compared to the Cytospin
method. CONCLUSIONS: The Thinprep method is more sensitive and suitable for LM
diagnosis in CSF in patients with malignant solid tumors than the Cytospin
method. The Thinprep method may facilitate primary tumor detection and help
design early treatment regimens for LM patients with tumors of unknown primary
origin.
PMID- 25850011
TI - Dioxygen activation and two consecutive oxidative decarboxylations of
phenylpyruvate by nonheme iron(II) complexes: functional models of
hydroxymandelate synthase (HMS) and CloR.
AB - Two mononuclear iron(ii)-phenylpyruvate complexes of monoanionic facial N3
ligands are reported to react with dioxygen to undergo two consecutive oxidative
decarboxylation steps via an iron-mandelate complex mimicking the function of HMS
and CloR.
PMID- 25850013
TI - Edaravone enhances brain-derived neurotrophic factor production in the ischemic
mouse brain.
AB - Edaravone, a clinical drug used to treat strokes, protects against neuronal cell
death and memory loss in the ischemic brains of animal models through its
antioxidant activity. In the present study, we subcutaneously administrated
edaravone to mice (3 mg/kg/day) for three days immediately after bilateral common
carotid artery occlusion, and revealed through an immunohistochemical analysis
that edaravone (1) accelerated increases in the production of brain-derived
neurotrophic factor (BDNF) in the hippocampus; (2) increased the number of
doublecortin-positive neuronal precursor cells in the dentate gyrus subgranular
zone; and (3) suppressed the ischemia-induced inactivation of calcium-calmodulin
dependent protein kinase II in the hippocampus. We also revealed through a
Western blotting analysis that edaravone (4) induced the phosphorylation of cAMP
response element-binding (CREB), a transcription factor that regulates BDNF gene
expression; and (5) induced the phosphorylation of extracellular signal-regulated
kinases 1/2, an upstream signal factor of CREB. These results suggest that the
neuroprotective effects of edaravone following brain ischemia were mediated not
only by the elimination of oxidative stress, but also by the induction of BDNF
production.
PMID- 25850012
TI - Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory
diseases.
AB - Excessive free radical generation, especially reactive oxygen species (ROS)
leading to oxidative stress in the biological system, has been implicated in the
pathogenesis and pathological conditions associated with diverse human
inflammatory diseases (HIDs). Although inflammation which is considered
advantageous is a defensive mechanism in response to xenobiotics and foreign
pathogen; as a result of cellular damage arising from oxidative stress, if
uncontrolled, it may degenerate to chronic inflammation when the ROS levels
exceed the antioxidant capacity. Therefore, in the normal resolution of
inflammatory reactions, apoptosis is acknowledged to play a crucial role, while
on the other hand, dysregulation in the induction of apoptosis by enhanced ROS
production could also result in excessive apoptosis identified in the
pathogenesis of HIDs. Apparently, a careful balance must be maintained in this
complex environment. Antimicrobial peptides (AMPs) have been proposed in this
review as an excellent candidate capable of playing prominent roles in
maintaining this balance. Consequently, in novel drug design for the treatment
and management of HIDs, AMPs are promising candidates owing to their size and
multidimensional properties as well as their wide spectrum of activities and
indications of reduced rate of resistance.
PMID- 25850014
TI - Enhancement of antiproliferative activity by phototautomerization of
anthrylphenols.
AB - An antiproliferative investigation was conducted on 3 human cancer cell lines,
HCT 116 (colon), MCF-7 (breast), and H 460 (lung), on a series of 4
anthrylphenols in the dark and upon exposure to light (350 nm). 9-(2
Hydroxyphenyl)anthracene (1) moderately inhibited proliferation, but irradiation
considerably enhanced the effect. The other anthracenes 4-6 exhibited
antiproliferative activity in the dark, which was not enhanced upon irradiation.
The enhancement of the antiproliferative effect on the irradiation of 1 was
rationalized as being due to the formation of quinone methide (QM 2) by excited
state proton transfer. QM 2 acts as an electrophilic species capable of reacting
with biological molecules. Although QM 2 reacts with nucleotides, the adducts
could not be isolated. On the contrary, cysteine adduct 8 was isolated and
characterized, whereas the adducts with glycine, serine and tripeptide
glutathione were characterized by MS. Non-covalent binding of 1 to DNA and bovine
serum albumin was demonstrated by UV-vis, fluorescence and CD spectroscopy.
However, a straightforward conclusion regarding the DNA or protein alkylating
(damaging) ability of 2 could not be drawn. The results obtained by the
irradiation of 1 in the presence of DNA, amino acids and peptides, cell cycle
perturbation analysis, and in vitro translation of GFP suggest that the effect is
not only due to the damage of DNA but also due to the impact on the cellular
proteins. Considering that to date all QM agents were assumed to target DNA
dominantly, this is an important finding with an impact on the further
development of anticancer agents based on QMs.
PMID- 25850015
TI - Correction: positive effects of bFGF modified rat amniotic epithelial cells
transplantation on transected rat optic nerve.
PMID- 25850016
TI - A stable chimeric fibroblast growth factor (FGF) can successfully replace basic
FGF in human pluripotent stem cell culture.
AB - Fibroblast growth factors (FGFs) are essential for maintaining self-renewal in
human embryonic stem cells and induced pluripotent stem cells. Recombinant basic
FGF (bFGF or FGF2) is conventionally used to culture pluripotent stem cells;
however, because of the instability of bFGF, repeated addition of fresh bFGF into
the culture medium is required in order to maintain its concentration. In this
study, we demonstrate that a heat-stable chimeric variant of FGF, termed FGFC,
can be successfully used for maintaining human pluripotent stem cells. FGFC is a
chimeric protein composed of human FGF1 and FGF2 domains that exhibits higher
thermal stability and protease resistance than do both FGF1 and FGF2. Both human
embryonic stem cells and induced pluripotent stem cells were maintained in
ordinary culture medium containing FGFC instead of FGF2. Comparison of cells
grown in FGFC with those grown in conventional FGF2 media showed no significant
differences in terms of the expression of pluripotency markers, global gene
expression, karyotype, or differentiation potential in the three germ lineages.
We therefore propose that FGFC may be an effective alternative to FGF2, for
maintenance of human pluripotent stem cells.
PMID- 25850017
TI - HATCH score in the prediction of new-onset atrial fibrillation after catheter
ablation of typical atrial flutter.
AB - BACKGROUND: New-onset atrial fibrillation (AF) is not uncommon after ablation of
typical atrial flutter (AFL); however, limited data are available for a risk
prediction model for the future occurrence of AF in patients with typical AFL
undergoing successful catheter ablation. OBJECTIVE: This study aimed to determine
whether the HATCH score (which is based on hypertension, age >=75 years,
transient ischemic attack or stroke, chronic obstructive pulmonary disease, and
heart failure) is useful for risk prediction of subsequent AF after ablation of
typical AFL. METHODS: A total of 216 consecutive patients presenting with typical
AFL and no history of AF who underwent successful catheter ablation were enrolled
in the study. The clinical endpoint was occurrence of new-onset AF during follow
up after ablation. RESULTS: During a follow-up period of 29.1 +/- 18.3 months, 85
patients (39%) experienced at least 1 episode of AF. Multivariate Cox regression
analysis demonstrated that the HATCH score (hazard ratio 1.784; 95% confidence
interval 1.352-2.324; P < .001) and left atrial diameter (hazard ratio 1.270; 95%
confidence interval 1.115-1.426; P < .001) were independently associated with new
onset AF after typical AFL ablation. The area under the receiver operator
characteristic curve based on the HATCH score for prediction of new-onset AF was
0.743. The HATCH score could be used to stratify the patients into 2 groups with
different incidences of new-onset AF (69% vs 27%, P < .001) at a cutoff value of
2. CONCLUSIONS: The HATCH score is a useful predictor of new-onset AF after
typical AFL ablation.
PMID- 25850018
TI - The Arabidopsis ethylene overproducer mutant eto1-3 displays enhanced freezing
tolerance.
AB - Low temperature is one of the most important environmental stresses constraining
plant development and distribution. Plants have evolved complex adaptive
mechanisms to face and survive freezing temperatures. Different signaling
pathways regulating plant response to cold have been described, and some of them
are mediated by hormones. Recently, we reported that ethylene (ET) acts as a
positive regulator of plant freezing tolerance through the activation of cold
induced gene expression, including the CBF-regulon. Here, we present data
demonstrating that the Arabidopsis ET overproducer mutant eto1-3 has enhanced
freezing tolerance. Moreover, we also show that this mutant exhibits increased
accumulation of CBF1, 2 and 3 transcripts, which should account for its tolerant
phenotype. All these results constitute new genetic evidence supporting an
important role for ET in plant response to low temperature by mediating the CBF
dependent signaling pathway.
PMID- 25850019
TI - Effectiveness of an oral cholera vaccine campaign to prevent clinically
significant cholera in Odisha State, India.
AB - BACKGROUND: A clinical trial conducted in India suggests that the oral cholera
vaccine, Shanchol, provides 65% protection over five years against clinically
significant cholera. Although the vaccine is efficacious when tested in an
experimental setting, policymakers are more likely to use this vaccine after
receiving evidence demonstrating protection when delivered to communities using
local health department staff, cold chain equipment, and logistics. METHODS: We
used a test-negative, case-control design to evaluate the effectiveness of a
vaccination campaign using Shanchol and validated the results using a cohort
approach that addressed disparities in healthcare seeking behavior. The campaign
was conducted by the local health department using existing resources in a
cholera-endemic area of Puri District, Odisha State, India. All non-pregnant
residents one year of age and older were offered vaccine. Over the next two
years, residents seeking care for diarrhea at one of five health facilities were
asked to enroll following informed consent. Cases were patients seeking treatment
for laboratory-confirmed V. cholera-associated diarrhea. Controls were patients
seeking treatment for V. cholerae negative diarrhea. RESULTS: Of 51,488 eligible
residents, 31,552 individuals received one dose and 23,751 residents received two
vaccine doses. We identified 44 V. cholerae O1-associated cases and 366 non V.
cholerae diarrhea controls. The adjusted protective effectiveness for persons
receiving two doses was 69.0% (95% CI: 14.5% to 88.8%), which is similar to the
adjusted estimates obtained from the cohort approach. A statistical trend test
suggested a single dose provided a modicum of protection (33%, test for trend,
p=0.0091). CONCLUSION: This vaccine was found to be as efficacious as the results
reported from a clinical trial when administered to a rural population using
local health personnel and resources. This study provides evidence that this
vaccine should be widely deployed by public health departments in cholera endemic
areas.
PMID- 25850020
TI - Targeting of rotavirus VP6 to DEC-205 induces protection against the infection in
mice.
AB - Rotavirus (RV) is the primary etiologic agent of severe gastroenteritis in human
infants. Although two attenuated RV-based vaccines have been licensed to be
applied worldwide, they are not so effective in low-income countries, and the
induced protection mechanisms have not been clearly established. Thus, it is
important to develop new generation vaccines that induce long lasting heterotypic
immunity. VP6 constitutes the middle layer protein of the RV virion. It is the
most conserved protein and it is the target of protective T-cells; therefore, it
is a potential candidate antigen for a new generation vaccine against the RV
infection. We determined whether targeting the DEC-205 present in dendritic cells
(DCs) with RV VP6 could induce protection at the intestinal level. VP6 was cross
linked to a monoclonal antibody (mAb) against murine DEC-205 (alphaDEC-205:VP6),
and BALB/c mice were inoculated subcutaneously (s.c.) twice with the conjugated
containing 1.5 MUg of VP6 in the presence of polyinosinic-polycytidylic acid
(Poly I:C) as adjuvant. As controls and following the same protocol, mice were
immunized with ovalbumin (OVA) cross-linked to the mAb anti-DEC-205 (alphaDEC
205:OVA), VP6 cross-linked to a control isotype mAb (Isotype:VP6), 3 MUg of VP6
alone, Poly I:C or PBS. Two weeks after the last inoculation, mice were orally
challenged with a murine RV. Mice immunized with alpha-DEC-205:VP6 and VP6 alone
presented similar levels of serum Abs to VP6 previous to the virus challenge.
However, after the virus challenge, only alpha-DEC-205:VP6 induced up to a 45%
IgA-independent protection. Memory T-helper (Th) cells from the spleen and the
mesenteric lymph node (MLN) showed a Th1-type response upon antigen stimulation
in vitro. These results show that when VP6 is administered parenterally targeting
DEC-205, it can induce protection at the intestinal level at a very low dose, and
this protection may be Th1-type cell dependent.
PMID- 25850021
TI - Increasing influenza vaccination in New York City taxi drivers: A community
driven approach.
AB - The Healthy People 2020 influenza immunization goal is 80% for non
institutionalized adults 18-64. However, vaccination rates remain stubbornly low.
Culturally tailored approaches to communities with poor vaccine uptake are
necessary. Taxi drivers are at risk for influenza and its complications, could
serve as vectors for influenza infection, and could be an effective vaccination
target to enhance herd immunity of the urban population. To the best of our
knowledge, this is the first study related to influenza vaccination among taxi
drivers. The NYC Taxi Network surveyed a convenience sample of 53 taxi drivers to
understand vaccination barriers. Only 17% had been vaccinated. Results informed a
pilot tailored workplace intervention, which resulted in vaccinations for 44% of
unvaccinated drivers. The study revealed that older drivers were more likely to
be vaccinated than younger drivers, while the most common barrier to immunization
was that drivers thought vaccination was 'not necessary'.
PMID- 25850022
TI - Evaluation of anthrax vaccine safety in 18 to 20 year olds: A first step towards
age de-escalation studies in adolescents.
AB - BACKGROUND/OBJECTIVES: Anthrax vaccine adsorbed (AVA, BioThrax((r))) is
recommended for post-exposure prophylaxis administration for the US population in
response to large-scale Bacillus anthracis spore exposure. However, no
information exists on AVA use in children and ethical barriers exist to
performing pre-event pediatric AVA studies. A Presidential Ethics Commission
proposed a potential pathway for such studies utilizing an age de-escalation
process comparing safety and immunogenicity data from 18 to 20 year-olds to older
adults and if acceptable proceeding to evaluations in younger adolescents. We
conducted exploratory summary re-analyses of existing databases from 18 to 20
year-olds (n=74) compared to adults aged 21 to 29 years (n=243) who participated
in four previous US government funded AVA studies. METHODS: Data extracted from
studies included elicited local injection-site and systemic adverse events (AEs)
following AVA doses given subcutaneously at 0, 2, and 4 weeks. Additionally,
proportions of subjects with >=4-fold antibody rises from baseline to post-second
and post-third AVA doses (seroresponse) were obtained. RESULTS: Rates of any
elicited local AEs were not significantly different between younger and older age
groups for local events (79.2% vs. 83.8%, P=0.120) or systemic events (45.4% vs.
50.5%, P=0.188). Robust and similar proportions of seroresponses to vaccination
were observed in both age groups. CONCLUSIONS: AVA was safe and immunogenic in 18
to 20 year-olds compared to 21 to 29 year-olds. These results provide initial
information to anthrax and pediatric specialists if AVA studies in adolescents
are required.
PMID- 25850024
TI - The effects of video-game training on broad cognitive transfer in multiple
sclerosis: A pilot randomized controlled trial.
AB - BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative disease of the central
nervous system that results in diffuse nerve damage and associated physical and
cognitive impairments. Of the few comprehensive rehabilitation options that exist
for populations with lower baseline cognitive functioning, those that have been
successful at eliciting broad cognitive improvements have focused on a multimodal
training approach, emphasizing complex cognitive processing that utilizes
multiple domains simultaneously. METHOD: The current study sought to determine
the feasibility of an 8-week, hybrid-variable priority training (HVT) program,
with a secondary aim to assess the success of this training paradigm at eliciting
broad cognitive transfer effects. Capitalizing on the multimodal training
modalities offered by the Space Fortress platform, we compared the HVT strategy
based intervention with a waitlist control group, to primarily assess skill
acquisition and secondarily determine presence of cognitive transfer. Twenty
eight participants met inclusionary criteria for the study and were randomized to
either training or waitlist control groups. To assess broad transfer effects, a
battery of neuropsychological tests was administered pre- and post-intervention.
RESULTS: The results indicated an overall improvement in skill acquisition and
evidence for the feasibility of the intervention, but a lack of broad transfer to
tasks of cognitive functioning. Participants in the training group, however, did
show improvements on a measure of spatial short-term memory. CONCLUSIONS: The
current investigation provided support for the feasibility of a multimodal
training approach, using the HVT strategy, within the MS population, but lacked
broad transfer to multiple domains of cognitive functioning. Future improvements
to obtain greater cognitive transfer efficacy would include a larger sample size,
a longer course of training to evoke greater game score improvement, the
inclusion of only cognitively impaired individuals, and integration of subjective
measures of improvement in addition to objective tests of cognitive performance.
PMID- 25850025
TI - Profiles of 21-Carbon Steroids in 21-hydroxylase Deficiency.
AB - CONTEXT: Marked elevations of 17-hydroxyprogesterone (17OHP) are characteristic
of classic 21-hydroxylase deficiency (21OHD). Testing of 17OHP provides the basis
for 21OHD diagnosis, although it suffers from several pitfalls. False-positive or
false-negative results and poor discrimination of nonclassic 21OHD from carriers
limit the utility of serum 17OHP and necessitate dynamic testing after
cosyntropin stimulation when values are indeterminate. OBJECTIVE: The objective
was to provide a detailed characterization of 21-carbon (C21) steroids in classic
21OHD, which might identify other candidate steroids that could be employed for
the diagnosis of 21OHD. SETTING AND PARTICIPANTS: Patients (11 women, 10 men)
with classic 21OHD and 21 sex- and age-matched controls seen in a tertiary
referral center were studied. METHODS: C21 steroids in the peripheral sera from
all subjects, as well as in media from cultured testicular adrenal rest tumor
(TART) cells and normal adrenal (NA) cells, were analyzed using liquid
chromatography/tandem mass spectrometry (10 steroids). Additionally, the dynamics
of C21 steroid metabolism in TART and NA cells were assessed with radiotracer
studies. RESULTS: Five C21 steroids were significantly higher in 21OHD patients:
17OHP (67-fold; P < .01), 21-deoxycortisol (21dF; 35-fold; P < .01), 16alpha
hydroxyprogesterone (16OHP; 28-fold; P < .01), progesterone (2-fold; P < .01),
and 11beta-hydroxyprogesterone (11OHP; not detected in controls; P < .01). The
same steroids were the highest in media from TART cells relative to the NA cells:
11OHP, 58- to 65-fold; 21dF, 30- to 41-fold; 17OHP, 9-fold; progesterone, 9- to
12-fold; and 16OHP, 7-fold. CONCLUSION: Measurement of 16OHP and 11OHP along with
17OHP and 21dF by liquid chromatography/tandem mass spectrometry might comprise a
biomarker panel to accurately diagnose all forms of 21OHD.
PMID- 25850026
TI - Measuring Estrogen Exposure and Metabolism: Workshop Recommendations on Clinical
Issues.
PMID- 25850027
TI - Discovery of a P450-catalyzed step in vindoline biosynthesis: a link between the
aspidosperma and eburnamine alkaloids.
AB - Here we report the discovery of a cytochrome P450 that is required for the
biosynthesis of vindoline, a plant-derived natural product used for semi
synthesis of several anti-cancer drugs. This enzyme catalyzes the formation of an
epoxide that can undergo rearrangement to yield the vincamine-eburnamine
backbone, thereby providing evidence for the long-standing hypothesis that the
aspidosperma- and eburnamine-type alkaloids are biosynthetically related.
PMID- 25850028
TI - Adenovirus-mediated transfer of the SOCS-1 gene to mouse lung confers protection
against hyperoxic acute lung injury.
AB - Suppressor of cytokine signaling-1 (SOCS-1) is a member of the suppressor of
cytokine signaling family of proteins and an inhibitor of interleukin-6 (IL-6)
signaling. SOCS-1 has been shown to protect cells from cellular damage and
apoptosis induced by tumor necrosis factor (TNF), lipopolysaccharide (LPS), and
interferon gamma (IL-gamma). However, it is not known whether increased SOCS-1 is
protective during pulmonary oxidative stress. Therefore, we hypothesized that
increased SOCS-1 in the lungs of mice would be protective in the setting of
hyperoxic lung injury. We administered SOCS-1 adenovirus (Ad-SOCS-1)
intratracheally into the lungs and exposed the mice to 100% O2. Mice infected
with GFP adenovirus (Ad-GFP) were used as controls. Mice treated with Ad-SOCS-1
had enhanced survival in 100% oxygen compared to Ad-GFP-administered mice. After
3 days of hyperoxia, Ad-GFP mice were ill and tachypnic and died after 4 days. In
contrast, all Ad-SOCS-1-treated mice survived for at least 6 days in hyperoxia
and 80% survived beyond 7 days. Ad-SOCS-1 transfection protected mouse lungs from
injury as indicated by lower lung wet/dry weight, alveolar-capillary protein
leakage, reduced infiltration of inflammatory cells, and lower content of
thiobarbituric acid-reactive substances in lung homogenate. Our results also
indicated that Ad-SOCS-1 significantly inhibits hyperoxia-induced ASK-1
(apoptosis signal-regulating kinase 1) expression. Taken together, these findings
show that increased expression of adenovirus-mediated SOCS-1 in the lungs of mice
significantly protects against hyperoxic lung injury.
PMID- 25850029
TI - Treatment of near-infrared photodynamic therapy using a liposomally formulated
indocyanine green derivative for squamous cell carcinoma.
AB - INTRODUCTION: Photodynamic therapy (PDT) is a less invasive option for cancer
treatment that has evolved through recent developments in nanotechnology. We have
designed and synthesized a novel liposome system that includes an indocyanine
green (ICG) derivative, ICG-C18, in its bilayer. In addition to its use as an
optical imager to visualize blood, lymphatic, and bile flow, ICG has also been
used as an optical sensitizer. In the present report, we evaluate the use of our
novel liposome system, LP-ICG-C18, in PDT for squamous cell carcinoma in an
autologous murine model. MATERIALS AND METHODS: An excitation pulse beam (300
MUJ/pulse) of a single band (800 nm) was used for sensitization. The cytotoxicity
of the photodynamic therapy was evaluated in terms of cellular morphology
changes, methyl thiazolyl tetrazolium (MTT) assay results, and terminal
deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end
labeling (TUNEL) staining. We tested the enhanced permeability and retention
effect of LP-ICG-C18 in tumor-bearing C3H/He mice using a near-infrared
fluorescence imaging system and fluorescence microscopy. We also examined the
antitumor effect of PDT by measuring tumor volume in tumor-bearing mice. RESULTS:
Cell death and apoptosis were only observed in the PDT group receiving LP-ICG
C18. LP-ICG-C18 itself had no cytotoxic activity and showed good
biocompatibility. LP-ICG-C18 accumulated on the tumor 24 hours after injection
and was retained for approximately 3 weeks. Tumor cell apoptosis following PDT
with LP-ICG-C18 was also observed under optical microscopy, MTT assay, and TUNEL
staining. CONCLUSION: These findings suggest that LP-ICG-C18 may be an effective
intervening material in PDT for malignant disease.
PMID- 25850030
TI - A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet
therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI
study.
AB - Treatment of carriers of the CYP2C19*2 allele and ABCB1 TT genotype with
clopidogrel is associated with increased ischemic complications after
percutaneous coronary intervention (PCI). We sought to evaluate a pharmacogenomic
strategy among patients undergoing PCI for ST-elevation myocardial infarction
(STEMI), by performing a randomized trial, enrolling 102 patients. Point-of-care
genetic testing for CYP2C19*2, ABCB1 TT and CYP2C19*17 was performed with
carriers of either the CYP2C19*2 allele or ABCB1 TT genotype randomly assigned to
a strategy of prasugrel 10 mg daily or an augmented dosing strategy of
clopidogrel (150 mg daily for 6 days then 75 mg daily). The primary end point was
the proportion of at-risk carriers exhibiting high on-treatment platelet
reactivity (HPR), a marker associated with increased adverse cardiovascular
events, after 1 month. Fifty-nine subjects (57.8%) were identified as carriers of
at least one at-risk variant. Treatment with prasugrel significantly reduced HPR
compared with clopidogrel by P2Y12 reaction unit (PRU) thresholds of >234 (0 vs
24.1%, P=0.0046) and PRU>208 (3.3 vs 34.5%, P=0.0025). The sensitivity of point
of-care testing was 100% (95% CI 88.0-100), 100% (86.3-100) and 96.9% (82.0-99.8)
and specificity was 97.0% (88.5-99.5), 97.1% (89.0-99.5) and 98.5% (90.9-99.9)
for identifying CYP2C19*2, ABCB1 TT and CYP2C19*17, respectively. Logistic
regression confirmed carriers as a strong predictor of HPR (OR=6.58, 95% CI 1.24
34.92; P=0.03). We confirmed that concurrent identification of three separate
genetic variants in patients with STEMI receiving PCI is feasible at the bedside.
Among carriers of at-risk genotypes, treatment with prasugrel was superior to an
augmented dosing strategy of clopidogrel in reducing HPR.
PMID- 25850031
TI - Neuronal cell adhesion genes and antidepressant response in three independent
samples.
AB - Drug-effect phenotypes in human lymphoblastoid cell lines recently allowed to
identify CHL1 (cell adhesion molecule with homology to L1CAM), GAP43 (growth
associated protein 43) and ITGB3 (integrin beta 3) as new candidates for
involvement in the antidepressant effect. CHL1 and ITGB3 code for adhesion
molecules, while GAP43 codes for a neuron-specific cytosolic protein expressed in
neuronal growth cones; all the three gene products are involved in synaptic
plasticity. Sixteen polymorphisms in these genes were genotyped in two samples
(n=369 and 90) with diagnosis of major depressive episode who were treated with
antidepressants in a naturalistic setting. Phenotypes were response, remission
and treatment-resistant depression. Logistic regression including appropriate
covariates was performed. Genes associated with outcomes were investigated in the
Sequenced Treatment Alternatives to Relieve Depression (STAR*D) genome-wide study
(n=1861) as both individual genes and through a pathway analysis (Reactome and
String databases). Gene-based analysis suggested CHL1 rs4003413, GAP43 rs283393
and rs9860828, ITGB3 rs3809865 as the top candidates due to their replication
across the largest original sample and the STAR*D cohort. GAP43 molecular pathway
was associated with both response and remission in the STAR*D, with ELAVL4
representing the gene with the highest percentage of single nucleotide
polymorphisms (SNPs) associated with outcomes. Other promising genes emerging
from the pathway analysis were ITGB1 and NRP1. The present study was the first to
analyze cell adhesion genes and their molecular pathways in antidepressant
response. Genes and biomarkers involved in neuronal adhesion should be considered
by further studies aimed to identify predictors of antidepressant response.
PMID- 25850032
TI - IL-6-mediated environmental conditioning of defective Th1 differentiation dampens
antitumour immune responses in old age.
AB - Decline in immune function and inflammation concomitantly develop with ageing.
Here we focus on the impact of this inflammatory environment on T cells, and
demonstrate that in contrast to successful tumour elimination in young mice,
replenishment of tumour-specific CD4(+) T cells fails to induce tumour regression
in aged hosts. The impaired antitumour effect of CD4(+) T cells with their
defective Th1 differentiation in an aged environment is restored by interleukin
(IL)-6 blockade or IL-6 deficiency. IL-6 blockade also restores the impaired
ability of CD4(+) T cells to promote CD8(+) T-cell-dependent tumour elimination
in aged mice, which requires IFN-gamma. Furthermore, IL-6-stimulated production
of IL-4/IL-21 through c-Maf induction is responsible for impaired Th1
differentiation. IL-6 also contributes to IL-10 production from CD4(+) T cells in
aged mice, causing attenuated responses of CD8(+) T cells. These findings suggest
that IL-6 serves as an extrinsic factor counteracting CD4(+) T-cell-mediated
immunity against tumour in old age.
PMID- 25850033
TI - Genetic variability and evolutionary diversification of membrane ABC transporters
in plants.
AB - BACKGROUND: ATP-binding cassette proteins have been recognized as playing a
crucial role in the regulation of growth and resistance processes in all kingdoms
of life. They have been deeply studied in vertebrates because of their role in
drug resistance, but much less is known about ABC superfamily functions in
plants. RESULTS: Recently released plant genome sequences allowed us to identify
803 ABC transporters in four vascular plants (Oryza. sativa, Solanum
lycopersicum, Solanum tuberosum and Vitis vinifera) and 76 transporters in the
green alga Volvox carteri, by comparing them with those reannotated in
Arabidopsis thaliana and the yeast Saccharomyces cerevisiae. Retrieved proteins
have been phylogenetically analysed to infer orthologous relationships. Most
orthologous relationships in the A, D, E and F subfamilies were found, and
interesting expansions within the ABCG subfamily were observed and discussed. A
high level of purifying selection is acting in the five ABC subfamilies A, B, C,
D and E. However, evolutionary rates of recent duplicate genes could influence
vascular plant genome diversification. The transcription profiles of ABC genes
within tomato organs revealed a broad functional role for some transporters and a
more specific activity for others, suggesting the presence of key ABC regulators
in tomato. CONCLUSIONS: The findings achieved in this work could contribute to
address several biological questions concerning the evolution of the relationship
between genomes of different species. Plant ABC protein inventories obtained
could be a valuable tool both for basic and applied studies. Indeed,
interpolation of the putative role of gene functions can accelerate the
discovering of new ABC superfamily members.
PMID- 25850035
TI - Standardization of Nanoparticle Characterization: Methods for Testing Properties,
Stability, and Functionality of Edible Nanoparticles.
AB - There has been a rapid increase in the fabrication of various kinds of edible
nanoparticles for oral delivery of bioactive agents, such as those constructed
from proteins, carbohydrates, lipids, and/or minerals. It is currently difficult
to compare the relative advantages and disadvantages of different kinds of
nanoparticle-based delivery systems because researchers use different analytical
instruments and protocols to characterize them. In this paper, we briefly review
the various analytical methods available for characterizing the properties of
edible nanoparticles, such as composition, morphology, size, charge, physical
state, and stability. This information is then used to propose a number of
standardized protocols for characterizing nanoparticle properties, for evaluating
their stability to environmental stresses, and for predicting their biological
fate. Implementation of these protocols would facilitate comparison of the
performance of nanoparticles under standardized conditions, which would
facilitate the rational selection of nanoparticle-based delivery systems for
different applications in the food, health care, and pharmaceutical industries.
PMID- 25850034
TI - Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine
mammary cancer cell aggressiveness.
AB - Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor.
Sialylation, governed by sialyltransferases and sialidases, is strongly
implicated in the oncogenesis and progression of breast cancer. In this study we
evaluated the biological behavior of canine mammary tumor cells upon oseltamivir
phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro
results showed that oseltamivir phosphate impairs sialidase activity leading to
increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells.
Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and
invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft
of oseltamivir phosphate-treated nude mice showed increased sialylation, namely
alpha2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards
increased lung metastases was observed in oseltamivir phosphate-treated nude
mice. Taken together, our findings revealed that oseltamivir impairs canine
mammary cancer cell sialidase activity, altering the sialylation pattern of
canine mammary tumors, and leading, surprisingly, to in vitro and in vivo
increased mammary tumor aggressiveness.
PMID- 25850037
TI - Rebooting review.
PMID- 25850038
TI - IDO inhibitors move center stage in immuno-oncology.
PMID- 25850040
TI - Pfizer's CDK4/6 inhibitor approved for advanced breast cancer.
PMID- 25850042
TI - Obama catapults patient-empowered Precision Medicine.
PMID- 25850036
TI - Targeting Cdc20 as a novel cancer therapeutic strategy.
AB - The Anaphase Promoting Complex (APC, also called APC/C) regulates cell cycle
progression by forming two closely related, but functionally distinct E3
ubiquitin ligase sub-complexes, APC(Cdc20) and APC(Cdh1), respectively. Emerging
evidence has begun to reveal that Cdc20 and Cdh1 have opposing functions in
tumorigenesis. Specifically, Cdh1 functions largely as a tumor suppressor,
whereas Cdc20 exhibits an oncogenic function, suggesting that Cdc20 could be a
promising therapeutic target for combating human cancer. However, the exact
underlying molecular mechanisms accounting for their differences in tumorigenesis
remain largely unknown. Therefore, in this review, we summarize the downstream
substrates of Cdc20 and the critical functions of Cdc20 in cell cycle
progression, apoptosis, ciliary disassembly and brain development. Moreover, we
briefly describe the upstream regulators of Cdc20 and the oncogenic role of Cdc20
in a variety of human malignancies. Furthermore, we summarize multiple
pharmacological Cdc20 inhibitors including TAME and Apcin, and their potential
clinical benefits. Taken together, development of specific Cdc20 inhibitors could
be a novel strategy for the treatment of human cancers with elevated Cdc20
expression.
PMID- 25850045
TI - Nonbrowning GM apple cleared for market.
PMID- 25850047
TI - Monsanto adds dicamba to its cache to counter weed threat.
PMID- 25850048
TI - Engineers of scent.
AB - Companies exploring biotech approaches to flavor and fragrance production must
navigate challenges in regulations, market dynamics and public perception. Emily
Waltz investigates.
PMID- 25850049
TI - Academic partnerships 2014.
PMID- 25850050
TI - First rounders podcast: Kari Stefansson.
PMID- 25850051
TI - The quintessence of immunogenicity reporting for biotherapeutics.
PMID- 25850052
TI - Silence on the relevant literature and errors in implementation.
PMID- 25850053
TI - Response to letter of correspondence - Bastiaens et al.
PMID- 25850054
TI - Opportunities for drug repositioning from phenome-wide association studies.
PMID- 25850055
TI - Are the gene-patent storm clouds dissipating? A global snapshot.
AB - In genetic diagnostics testing, what are the boundaries of the global patent
problem, and is there a real risk that patents and licensing practices could
impede access to tests?
PMID- 25850057
TI - Improving reference epigenome catalogs by computational prediction.
PMID- 25850058
TI - A dynamic picture of protein behavior in cells.
PMID- 25850059
TI - Genetic variation and alternative splicing.
PMID- 25850061
TI - Federalist principles for healthcare data networks.
AB - Applying federalist principles to networked health record data could facilitate
realization of the potential of shared health data.
PMID- 25850062
TI - Corrigendum: Network deconvolution as a general method to distinguish direct
dependencies in networks.
PMID- 25850063
TI - Expanding ELSI to all areas of innovative science and technology.
AB - New curricula in the study of the ethical, legal and social implications of
scientific research aims to further the conversation among all stakeholders in
the interactions between science, technology and society.
PMID- 25850065
TI - Photoluminescent silicon nanocrystal-polymer hybrid materials via surface
initiated reversible addition-fragmentation chain transfer (RAFT) polymerization.
AB - Silicon-polymer core-shell hybrid materials are obtained via surface initiated
reversible addition-fragmentation chain transfer (RAFT) polymerization from
photoluminescent silicon nanocrystals (SiNCs). Polymer grafted SiNCs and free
polymers in solution are separated using ultracentrifugation. The polymerization
on the surface proceeds in a living manner which is confirmed via GPC, DLS and
TGA measurements. This method was applied to various other monomers. The obtained
materials all show bright red photoluminescence originating from the SiNC core.
PMID- 25850067
TI - A method for improving the pose accuracy of a robot manipulator based on multi
sensor combined measurement and data fusion.
AB - An improvement method for the pose accuracy of a robot manipulator by using a
multiple-sensor combination measuring system (MCMS) is presented. It is composed
of a visual sensor, an angle sensor and a series robot. The visual sensor is
utilized to measure the position of the manipulator in real time, and the angle
sensor is rigidly attached to the manipulator to obtain its orientation. Due to
the higher accuracy of the multi-sensor, two efficient data fusion approaches,
the Kalman filter (KF) and multi-sensor optimal information fusion algorithm
(MOIFA), are used to fuse the position and orientation of the manipulator. The
simulation and experimental results show that the pose accuracy of the robot
manipulator is improved dramatically by 38%~78% with the multi-sensor data
fusion. Comparing with reported pose accuracy improvement methods, the primary
advantage of this method is that it does not require the complex solution of the
kinematics parameter equations, increase of the motion constraints and the
complicated procedures of the traditional vision-based methods. It makes the
robot processing more autonomous and accurate. To improve the reliability and
accuracy of the pose measurements of MCMS, the visual sensor repeatability is
experimentally studied. An optimal range of 1 x 0.8 x 1 ~ 2 x 0.8 x 1 m in the
field of view (FOV) is indicated by the experimental results.
PMID- 25850066
TI - Difference in the electromyographic onset of the deep and superficial multifidus
during shoulder movement while standing.
AB - Based on the current literature, it remains unclear whether electromyographic
onset of the deep fibers of the multifidus (DM) is dependent on the direction of
shoulder movement and the position of the center of foot pressure (CFP). In the
present study, we re-examined the electromyographic onset of the DM during
shoulder flexion and extension and investigated the influence of the CFP position
before arm movement. Intramuscular and surface electrodes recorded the
electromyographic onset of the DM, superficial fibers of the multifidus (SM),
rectus abdominis, and anterior and posterior deltoid. Eleven healthy participants
performed rapid, unilateral shoulder flexion and extension in response to audio
stimuli at three CFP positions: quiet standing, extreme forward leaning, and
extreme backward leaning. It was found that the electromyographic onset of the DM
and SM relative to the deltoid was dependent on the direction of arm movement.
Additionally, of all electromyographic onsets recorded, only that of the DM
occurred earlier in the extreme forward leaning position than in the extreme
backward leaning position during shoulder flexion. These results suggest that the
electromyographic onset of DM was influenced by the biomechanical disturbance
such as shoulder movement and CFP position.
PMID- 25850068
TI - Fast video encryption using the H.264 error propagation property for smart mobile
devices.
AB - In transmitting video data securely over Video Sensor Networks (VSNs), since
mobile handheld devices have limited resources in terms of processor clock speed
and battery size, it is necessary to develop an efficient method to encrypt video
data to meet the increasing demand for secure connections. Selective encryption
methods can reduce the amount of computation needed while satisfying high-level
security requirements. This is achieved by selecting an important part of the
video data and encrypting it. In this paper, to ensure format compliance and
security, we propose a special encryption method for H.264, which encrypts only
the DC/ACs of I-macroblocks and the motion vectors of P-macroblocks. In
particular, the proposed new selective encryption method exploits the error
propagation property in an H.264 decoder and improves the collective performance
by analyzing the tradeoff between the visual security level and the processing
speed compared to typical selective encryption methods (i.e., I-frame, P-frame
encryption, and combined I-/P-frame encryption). Experimental results show that
the proposed method can significantly reduce the encryption workload without any
significant degradation of visual security.
PMID- 25850069
TI - Simulation methods for solvent vapor annealing of block copolymer thin films.
AB - Recent progress in modelling the solvent vapor annealing of thin film block
copolymers is examined in the context of a self-consistent field theory
framework. Key control variables in determining the final microdomain
morphologies include swelling ratio or swollen film solvent volume fraction,
swollen film thickness, substrate and vapor atmosphere surface energies,
effective volume fraction, and effective Flory-Huggins interaction parameter. The
regime of solvent vapor annealing studied is where the block copolymer has a high
enough Flory-Huggins parameter that ordered structures form during swelling and
are then trapped in the system through quenching. Both implicit and explicit
consideration of the solvent vapor is considered to distinguish the cases in
which solvent vapor leads to a non-bulk morphology. Block-selective solvents are
considered based on the experimental systems of polystyrene-b
polydimethylsiloxane annealed with toluene and heptane. The results of these
simulations are compared with these experiments.
PMID- 25850070
TI - Use of Historical Case Duration Data for Estimating the Duration of Future Cases.
PMID- 25850071
TI - Adolescent Endometriosis: Report of a Series of 55 Cases With a Focus on Clinical
Presentation and Long-Term Issues.
AB - STUDY OBJECTIVE: To report the clinical presentation and long-term issues of
adolescent endometriosis. DESIGN: Retrospective cohort study. SETTING: Single
private clinical center, Bordeaux, France. PATIENTS: Adolescents with a confirmed
diagnosis of endometriosis. INTERVENTIONS: Surgical excision or ablation or
lesions performed at laparoscopy. MEASUREMENTS AND MAIN RESULTS: Fifty-five
adolescents, ages from 12 to 19 years (mean age 17.8), who were diagnosed with
endometriosis from March 1998 to April 2013 were included in the study. Pain of
various types was the leading symptom in all patients, except 2. Twenty-three
patients had an adnexal mass identified preoperatively, and 5 had an associated
infertility issue at the time of diagnostic laparoscopy. Four patients had an
associated genital malformation. Fifty-one percent of the patients had a history
of appendectomy. A familial history of endometriosis was reported by 19 patients
(34.5%), with a first-degree relative affected in 14 cases (25.45%), and 47.3% of
patients were smoking at least 5 cigarettes a day. Superficial implants was
encountered in 31 cases (56.4%), endometriomas in 18 cases (32.72%), and deep
infiltrating endometriosis (DIE) in 6 cases (10.90%). Sixty percent of patients
were scored as stages I to II and 40% as stages III to IV. Five patients were
lost to follow-up, and 37 had a follow-up ranging from 36 to 315 months (mean
follow-up 125.5 months). Among the 50 patients not lost to follow-up, 13 (26%)
had either no pain, or improved and had acceptable pain with medical treatment.
Seventeen patients of the 50 adolescents not lost to follow-up (34%) underwent a
repeat laparoscopy. A subsequent laparoscopic and/or magnetic resonance imaging
scan was performed in 35 patients because of persistent pain. Among these, there
was 12 endometriomas (7 recurrences) and 12 DIEs (3 recurrences), giving
recurrence rates for endometriomas and DIEs of 36.84% and 50%, respectively.
During the study, 18 patients wished to have a child. Thirteen had a delivery
(72.2%), and 9 pregnancies occurred in patients who initially presented with
stage I to II endometriosis. Of the 11 patients who had subfertility, 6
successfully conceived (54.5%). CONCLUSIONS: Adolescent endometriosis is not a
rare condition. In our study a familial history was reported in more than one
third of patients. Among those patients treated for DIE, there was a trend for
higher rates of recurrences (symptoms or lesions) that required repeat
laparoscopy. However, the impact on subsequent fertility appeared to have been
limited.
PMID- 25850072
TI - Reply: To PMID 25020086.
PMID- 25850074
TI - The synergistic mechanism of graphene and MoS2 for hydrogen generation: insights
from density functional theory.
AB - The synergistic effect of graphene and MoS2 was investigated by using density
functional theory (DFT) calculations on the enhanced photocatalytic H2 production
activity of TiO2/graphene/MoS2 ternary nanoparticles. Our results indicate that
it can form a weak covalent bond between the Ti atom of TiO2 nanocluster and the
nearest C atom on graphene, which not only makes the original degenerate C(2p)
orbital level of the graphene (part of the conduction band energy level) split,
resulting in the production of a lower level of C(2p) that makes it easier to
accept the excited electron from the Ti(3d) orbital, but also forms a +/-
sequence electric field in the interface between them. It is conclusive that the
electron moves from the TiO2 cluster to the graphene. In addition, we also find
that the band gap of the TiO2 cluster can be doped by the graphene and MoS2, and
the conduction band consists predominantly of C(2p), S(3p) and Mo(4d) orbital
energy level near the Fermi level. These results illustrate that the excited
electron will eventually accumulate in the graphene or MoS2 film, which can
effectively enhance the separation between the excited electrons and the holes in
the TiO2 clusters, thereby increasing the efficiency of hydrogen evolution. Our
results are consistent with the experimental results, and can provide some
valuable information for the design of photocatalytic composites.
PMID- 25850073
TI - Laparoscopic Ureteroneocystostomy: Be Prepared!
AB - STUDY OBJECTIVE: To assess the outcomes and complications of laparoscopic
ureteroneocystotomy in gynecologic surgery. DESIGN: We retrospectively reviewed
all medical records of patients who underwent ureteroneocystostomy between April
2008 and May 2012. DESIGN CLASSIFICATION: Retrospective case series study.
SETTING: A university tertiary care hospital. PATIENTS: Nine patients underwent
ureteroneocystostomy: 3 patients had ureteral endometriosis stenoses; and 6
patients had iatrogenic ureter injuries. INTERVENTIONS: All procedures were
performed laparoscopically. The ureterovesical re-implantation was unilateral in
8 cases and bilateral for 1 patient. MEASUREMENTS AND MAIN RESULTS: The mean
operating time was 226.7 min (range, 120-480). Average blood loss was 114.4 mL
(range, 30-400). The mean duration of the in-dwelling catheter was 10.4 days
(range, 7-21); the average hospital stay was 12.6 days (range, 6-26). The mean
duration of the ureteral double J stent was 7.8 weeks (range, 6-16). One patient
was re-operated for vaginal and laparoscopic drainage of a pelvic abscess on the
sixth postoperative day. The median follow-up time was 20.8 months (range, 9-36),
No patient had stenosis or breakdown of a suture line. CONCLUSIONS: Our series
confirms the feasibility and the effectiveness of laparoscopic
ureteroneocystostomy. This minimally invasive approach, which avoids laparotomy,
requires a multidisciplinary team.
PMID- 25850075
TI - The use of rat spinal reflexes to quantify injection pain.
AB - Pain caused by subcutaneous injections is unpleasant, which may limit patient
compliance. The objective of this study was to use spinal reflexes to quantify
subcutaneous injection pain. Spinal reflexes were measured using an
electromyogram (EMG) test. The effects of injection volume, pH and osmotic
pressure were investigated. The EMG responses increased with injection volume and
the acidity of the solution but did not depend on the osmotic pressure of the
solution. The EMG responses differed for subcutaneously injected sodium chloride
and glucose over the same range of osmotic pressures. Pain caused by the
subcutaneous injections was unrelated to the osmotic ratio up to approximately 5.
The injection pain caused by therapeutic protein solutions was also evaluated. We
compared the EMG responses of the adalimumab and etanercept, as the injection of
adalimumab is more painful than that of etanercept in humans. The EMG magnitude
for adalimumab was twice that induced by etanercept as observed for the EMG tests
performed in rats. Therapeutic proteins account for an increasingly large
proportion of pharmaceutical drugs. When a high dose of therapeutic proteins is
required, the protein solution must often be highly concentrated to reduce the
injection volume. For patient comfort, it is critical to reduce injection pain.
The EMG test reported here allows subcutaneous injection pain to be quantified
and may be useful for optimizing drug formulations.
PMID- 25850076
TI - Tamoxifen-dependent, inducible Bmp2CreER drives selective recombinase activity in
early interdigital mesenchyme and digit collateral ligaments.
AB - During limb development, the interdigital mesenchyme has been proposed to play a
signaling role instructing morphogenesis of different digit types, as well as
undergoing programmed cell death necessary to free digits in animals not adapted
for swimming or flying. We have generated a conditional, tamoxifen-dependent Cre
line, Bmp2CreER, which drives highly selective recombination restricted to the
distal limb mesoderm, largely restricted to the interdigits, and selectively
active in digit ligament but not tendon progenitors at later stages. The
Bmp2CreER provides a valuable new tool to dissect roles of interdigital
mesenchyme and potentially investigate divergence of ligament and tendon
lineages.
PMID- 25850077
TI - Models of cortical malformation--Chemical and physical.
AB - Pharmaco-resistant epilepsies, and also some neuropsychiatric disorders, are
often associated with malformations in hippocampal and neocortical structures.
The mechanisms leading to these cortical malformations causing an imbalance
between the excitatory and inhibitory system are largely unknown. Animal models
using chemical or physical manipulations reproduce different human pathologies by
interfering with cell generation and neuronal migration. The model of in utero
injection of methylazoxymethanol (MAM) acetate mimics periventricular nodular
heterotopia. The freeze lesion model reproduces (poly)microgyria, focal
heterotopia and schizencephaly. The in utero irradiation model causes microgyria
and heterotopia. Intraperitoneal injections of carmustine 1-3-bis-chloroethyl
nitrosurea (BCNU) to pregnant rats produces laminar disorganization, heterotopias
and cytomegalic neurons. The ibotenic acid model induces focal cortical
malformations, which resemble human microgyria and ulegyria. Cortical dysplasia
can be also observed following prenatal exposure to ethanol, cocaine or
antiepileptic drugs. All these models of cortical malformations are characterized
by a pronounced hyperexcitability, few of them also produce spontaneous epileptic
seizures. This dysfunction results from an impairment in GABAergic inhibition
and/or an increase in glutamatergic synaptic transmission. The cortical region
initiating or contributing to this hyperexcitability may not necessarily
correspond to the site of the focal malformation. In some models wide-spread
molecular and functional changes can be observed in remote regions of the brain,
where they cause pathophysiological activities. This paper gives an overview on
different animal models of cortical malformations, which are mostly used in
rodents and which mimic the pathology and to some extent the pathophysiology of
neuronal migration disorders associated with epilepsy in humans.
PMID- 25850078
TI - A novel videographic method for quantitatively tracking vibrissal motor recovery
following facial nerve injuries in rats.
AB - BACKGROUND: Previous studies of vibrissal movements employ either optoelectronic
recording techniques in the head fixed rodent, or videographic recordings in
freely moving animals. However, both approaches have shortcomings for
quantitatively tracking the process of vibrissal motor recovery. NEW METHOD: A
critical feature of our videographic method is to measure tagged vibrissae
movements while leaving all others intact in body restrained rats without head
fixation. Thirty two adult rats underwent facial nerve manipulation and testing.
All animals underwent baseline preoperative whisking testing. In the experimental
groups, the right facial nerve was either crushed, or transected and sutured. In
the control groups, the left facial nerve underwent either sham surgery, or
transection denervation. Whisking function was measured for the ensuing 2 to 12
weeks. Data were analyzed for whisking recovery. RESULTS: Baseline preoperative
whisking testing showed that majority of free whisking on the both sides is
synchronous and symmetric, which allows us to compare vibrissal motor data
between intact and manipulated side after facial nerve injury. As expected, the
recovery of whisking function following crush is better and earlier than that
with transection and suture. COMPARISON WITH EXISTING METHOD(S): To our
knowledge, this novel videographic method is a significant simplification over
currently employed optoelectronic recording techniques and videographic methods.
CONCLUSIONS: Our novel videographic method may be a powerful tool to investigate
motor recovery from facial nerve manipulation in the rat model.
PMID- 25850079
TI - Activation of 5-HT1A receptors in the preBotzinger region has little impact on
the respiratory pattern.
AB - The preBotzinger (preBotC) complex has been suggested as the primary site where
systemically administered selective serotonin agonists have been shown to reduce
or prevent opioid-induced depression of breathing. However, this hypothesis has
not been tested pharmacologically in vivo. This study sought to determine whether
5-HT1A receptors within the preBotC and ventral respiratory column (VRC) mediate
the tachypneic response induced by intravenous (IV) (+/-)-8-Hydroxy-2
diproplyaminotetralin hydrobromide (8-OH-DPAT) in a decerebrated dog model. IV 8
OH-DPAT (19 +/- 2 MUg/kg) reduced both inspiratory (I) and expiratory (E)
durations by ~ 40%, but had no effect on peak phrenic activity (PPA).
Picoejection of 1, 10, and 100 MUM 8-OH-DPAT on I and E preBotC neurons produced
dose-dependent decreases up to ~ 40% in peak discharge. Surprisingly,
microinjections of 8-OH-DPAT and 5-HT within the VRC from the obex to 9 mm
rostral had no effect on timing and PPA. These results suggest that the
tachypneic effects of IV 8-OH-DPAT are due to receptors located outside of the
areas we studied.
PMID- 25850080
TI - Association of the biomarkers soluble ST2, galectin-3 and growth-differentiation
factor-15 with heart failure and other non-cardiac diseases.
AB - BACKGROUND: The biomarkers soluble ST2 (sST2), galectin-3, and growth
differentiation factor-15 (GDF-15) provide prognostic information in patients
with heart failure (HF). The aim of this study was to evaluate to which extent
plasma concentrations of these biomarkers are increased in HF compared with
diverse non-cardiac conditions such as infectious disease or chronic kidney
disease. METHODS: We recruited 15 patients in each of the following clinical
categories: HF without co-morbidity, pneumonia without co-morbidity, chronic
obstructive pulmonary disease (COPD) without co-morbidity, HF and a co-morbidity
of pneumonia, renal disease without co-morbidity, and sepsis. We used 22 healthy
individuals as control group. In each of the 112 study participants, we measured
plasma concentrations of sST2 (Presage assay), galectin-3 (Abbott assay) and GDF
15 (Roche assay). RESULTS: Compared to controls, the median sST2 concentration
was ~2.5-fold increased in HF, ~3.5-fold in pneumonia, ~5.0-fold in COPD, ~5.8
fold in HF+pneumonia, and ~70-fold in sepsis (p<0.001 for all). sST2 was not
significantly increased in renal disease. Compared to controls, the median
galectin-3 concentration was ~1.5-fold increased in HF, ~1.4-fold in pneumonia,
~2.4-fold in HF+pneumonia, ~2.5-fold in renal disease, and ~2.7-fold in sepsis
(p<0.001 for all). Galectin-3 was not significantly increased in COPD. Compared
to controls, the median GDF-15 concentration was ~4.4-fold increased in HF, ~5.4
fold in pneumonia, ~2.1-fold in COPD, ~8.3-fold in HF+pneumonia, ~5.1-fold in
renal disease, and ~27-fold in sepsis (p<0.001). In the 112 study participants,
correlation analyses revealed a relatively strong association between galectin-3
and GDF-15 (correlation coefficient, 0.739; p<0.001). CONCLUSION: Because
increased plasma concentrations of sST2, galectin-3, and GDF-15 are not specific
for a distinct disease group, the three biomarkers are not useful for diagnostic
purposes. The results of our study are novel with respect to sST2, galectin-3 and
GDF-15 as markers of inflammatory diseases and should encourage further studies.
PMID- 25850081
TI - Modeling Implantable Passive Mechanisms for Modifying the Transmission of Forces
and Movements Between Muscle and Tendons.
AB - This paper explores the development of biomechanical models for evaluating a new
class of passive mechanical implants for orthopedic surgery. The proposed
implants take the form of passive engineered mechanisms, and will be used to
improve the functional attachment of muscles to tendons and bone by modifying the
transmission of forces and movement inside the body. Specifically, we present how
two types of implantable mechanisms may be modeled in the open-source
biomechanical software OpenSim. The first implant, which is proposed for hand
tendon-transfer surgery, differentially distributes the forces and movement from
one muscle across multiple tendons. The second implant, which is proposed for
knee-replacement surgery, scales up the forces applied to the knee joint by the
quadriceps muscle. This paper's key innovation is that such mechanisms have never
been considered before in biomechanical simulation modeling and in surgery. When
compared with joint function enabled by the current surgical practice of using
sutures to make the attachment, biomechanical simulations show that the surgery
with 1) the differential mechanism (tendon network) implant improves the fingers'
ability to passively adapt to an object's shape significantly during grasping
tasks (2.74* as measured by the extent of finger flexion) for the same muscle
force, and 2) the force-scaling implant increases knee-joint torque by 84% for
the same muscle force. The critical significance of this study is to provide a
methodology for the design and inclusion of the implants into biomechanical
models and validating the improvement in joint function they enable when compared
with current surgical practice.
PMID- 25850082
TI - A Dual-Mode Large-Arrayed CMOS ISFET Sensor for Accurate and High-Throughput pH
Sensing in Biomedical Diagnosis.
AB - GOAL: The existing ISFET-based DNA sequencing detects hydrogen ions released
during the polymerization of DNA strands on microbeads, which are scattered into
microwell array above the ISFET sensor with unknown distribution. However, false
pH detection happens at empty microwells due to crosstalk from neighboring
microbeads. In this paper, a dual-mode CMOS ISFET sensor is proposed to have
accurate pH detection toward DNA sequencing. METHODS: Dual-mode sensing, optical
and chemical modes, is realized by integrating a CMOS image sensor (CIS) with
ISFET pH sensor, and is fabricated in a standard 0.18-MUm CIS process. With
accurate determination of microbead physical locations with CIS pixel by contact
imaging, the dual-mode sensor can correlate local pH for one DNA slice at one
location-determined microbead, which can result in improved pH detection
accuracy. Moreover, toward a high-throughput DNA sequencing, a correlated-double
sampling readout that supports large array for both modes is deployed to reduce
pixel-to-pixel nonuniformity such as threshold voltage mismatch. RESULTS: The
proposed CMOS dual-mode sensor is experimentally examined to show a well
correlated pH map and optical image for microbeads with a pH sensitivity of 26.2
mV/pH, a fixed pattern noise (FPN) reduction from 4% to 0.3%, and a readout speed
of 1200 frames/s. CONCLUSION: A dual-mode CMOS ISFET sensor with suppressed FPN
for accurate large-arrayed pH sensing is proposed and demonstrated with state-of
the-art measured results toward accurate and high-throughput DNA sequencing.
SIGNIFICANCE: The developed dual-mode CMOS ISFET sensor has great potential for
future personal genome diagnostics with high accuracy and low cost.
PMID- 25850083
TI - Aliasing Artefact Suppression in Compressed Sensing MRI for Random Phase-Encode
Undersampling.
AB - GOAL: Random phase-encode undersampling of Cartesian k-space trajectories is
widely implemented in compressed sensing (CS) MRI. However, its one-dimensional
(1-D) randomness inherently introduces large coherent aliasing artefacts along
the undersampled direction in the reconstruction and, thus, degrades the image
quality. This paper proposes a novel reconstruction scheme to reduce the 1-D
undersampling-induced aliasing artefacts. METHODS: The proposed reconstruction
progress is separated into two steps in our new algorithm. In step one, we
transfer the original two-dimensional (2-D) image reconstruction into a parallel
1-D signal reconstruction procedure, which takes advantage of the superior
incoherence property in the phase direction. In step two, using the new k-space
data obtained from the 1-D reconstructions, we implement a follow-up 2-D CS
reconstruction to produce a better solution, which exploits the inherent
correlations between the adjacent lines of 1-D reconstructed signals. RESULTS: We
evaluated the performance on various cases of typical MR images, including
cardiac cine, brain, foot, and angiogram at the reduction factor up to 10 and
compared the results with the conventional CS method. Experiments using the
proposed method demonstrated faithful reconstruction of the MR images.
CONCLUSION: Compared with conventional method, the new method achieves more
accurate reconstruction results with 2-5 dB gain in peak SNR and higher
structural similarity index. SIGNIFICANCE: The proposed method improves image
quality of the reconstructions and suppresses the coherent artefacts introduced
by the random phase-encode undersampling.
PMID- 25850084
TI - The Role of Pulse Repetition Rate in nsPEF-Induced Electroporation: A Biological
and Numerical Investigation.
AB - The impact of pulse repetition rate (PRR) in modulating electroporation (EP)
induced by nanosecond pulsed electric fields (nsPEFs) in mammalian cells was
approached here by performing both biological and numerical analysis. Plasma
membrane permeabilization and viability of Jurkat cells were analyzed after
exposure to 500, 1.3 MV/m, 40 ns PEFs with variable PRR (2-30 Hz). A finite
element model was used to investigate EP dynamics in a single cell under the same
pulsing conditions, by looking at the time course of transmembrane voltage and
pore density on the ns time scale. The biological observations showed an
increased EP and reduced viability of the exposed cells at lower PRR in the
considered range. The numerical analysis resulted in different dynamics of plasma
membrane response when ns pulses were delivered with different PRR, consistently
with a phenomenon of electrodesensitization recently hypothesized by another
research group.
PMID- 25850085
TI - Saliency based ulcer detection for wireless capsule endoscopy diagnosis.
AB - Ulcer is one of the most common symptoms of many serious diseases in the human
digestive tract. Especially for the ulcers in the small bowel where other
procedures cannot adequately visualize, wireless capsule endoscopy (WCE) is
increasingly being used in the diagnosis and clinical management. Because WCE
generates large amount of images from the whole process of inspection, computer
aided detection of ulcer is considered an indispensable relief to clinicians. In
this paper, a two-staged fully automated computer-aided detection system is
proposed to detect ulcer from WCE images. In the first stage, we propose an
effective saliency detection method based on multi-level superpixel
representation to outline the ulcer candidates. To find the perceptually and
semantically meaningful salient regions, we first segment the image into multi
level superpixel segmentations. Each level corresponds to different initial
region sizes of the superpixels. Then we evaluate the corresponding saliency
according to the color and texture features in superpixel region of each level.
In the end, we fuse the saliency maps from all levels together to obtain the
final saliency map. In the second stage, we apply the obtained saliency map to
better encode the image features for the ulcer image recognition tasks. Because
the ulcer mainly corresponds to the saliency region, we propose a saliency max
pooling method integrated with the Locality-constrained Linear Coding (LLC)
method to characterize the images. Experiment results achieve promising 92.65%
accuracy and 94.12% sensitivity, validating the effectiveness of the proposed
method. Moreover, the comparison results show that our detection system
outperforms the state-of-the-art methods on the ulcer classification task.
PMID- 25850086
TI - Bayesian model selection for pathological neuroimaging data applied to white
matter lesion segmentation.
AB - In neuroimaging studies, pathologies can present themselves as abnormal intensity
patterns. Thus, solutions for detecting abnormal intensities are currently under
investigation. As each patient is unique, an unbiased and biologically plausible
model of pathological data would have to be able to adapt to the subject's
individual presentation. Such a model would provide the means for a better
understanding of the underlying biological processes and improve one's ability to
define pathologically meaningful imaging biomarkers. With this aim in mind, this
work proposes a hierarchical fully unsupervised model selection framework for
neuroimaging data which enables the distinction between different types of
abnormal image patterns without pathological a priori knowledge. Its application
on simulated and clinical data demonstrated the ability to detect abnormal
intensity clusters, resulting in a competitive to improved behavior in white
matter lesion segmentation when compared to three other freely-available
automated methods.
PMID- 25850087
TI - Multi-dimensional complete ensemble empirical mode decomposition with adaptive
noise applied to laser speckle contrast images.
AB - Laser speckle contrast imaging (LSCI) is a noninvasive full-field optical
technique which allows analyzing the dynamics of microvascular blood flow. LSCI
has attracted attention because it is able to image blood flow in different kinds
of tissue with high spatial and temporal resolutions. Additionally, it is simple
and necessitates low-cost devices. However, the physiological information that
can be extracted directly from the images is not completely determined yet. In
this work, a novel multi-dimensional complete ensemble empirical mode
decomposition with adaptive noise (MCEEMDAN) is introduced and applied in LSCI
data recorded in three physiological conditions (rest, vascular occlusion and
post-occlusive reactive hyperaemia). MCEEMDAN relies on the improved complete
ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and our
algorithm is specifically designed to analyze multi-dimensional data (such as
images). Over the recent multi-dimensional ensemble empirical mode decomposition
(MEEMD), MCEEMDAN has the advantage of leading to an exact reconstruction of the
original data. The results show that MCEEMDAN leads to intrinsic mode functions
and residue that reveal hidden patterns in LSCI data. Moreover, these patterns
differ with physiological states. MCEEMDAN appears as a promising way to extract
features in LSCI data for an improvement of the image understanding.
PMID- 25850088
TI - Sorted consecutive local binary pattern for texture classification.
AB - In this paper, we propose a sorted consecutive local binary pattern (scLBP) for
texture classification. Conventional methods encode only patterns whose spatial
transitions are not more than two, whereas scLBP encodes patterns regardless of
their spatial transition. Conventional methods do not encode patterns on account
of rotation-invariant encoding; on the other hand, patterns with more than two
spatial transitions have discriminative power. The proposed scLBP encodes all
patterns with any number of spatial transitions while maintaining their rotation
invariant nature by sorting the consecutive patterns. In addition, we introduce
dictionary learning of scLBP based on kd-tree which separates data with a space
partitioning strategy. Since the elements of sorted consecutive patterns lie in
different space, it can be generated to a discriminative code with kd-tree.
Finally, we present a framework in which scLBPs and the kd-tree can be combined
and utilized. The results of experimental evaluation on five texture data sets-
Outex, CUReT, UIUC, UMD, and KTH-TIPS2-a--indicate that our proposed framework
achieves the best classification rate on the CUReT, UMD, and KTH-TIPS2-a data
sets compared with conventional methods. The results additionally indicate that
only a marginal difference exists between the best classification rate of
conventional methods and that of the proposed framework on the UIUC and Outex
data sets.
PMID- 25850089
TI - Effects of Innovative WALKBOT Robotic-Assisted Locomotor Training on Balance and
Gait Recovery in Hemiparetic Stroke: A Prospective, Randomized, Experimenter
Blinded Case Control Study With a Four-Week Follow-Up.
AB - The present clinical investigation was to ascertain whether the effects of
WALKBOT-assisted locomotor training (WLT) on balance, gait, and motor recovery
were superior or similar to the conventional locomotor training (CLT) in patients
with hemiparetic stroke. Thirty individuals with hemiparetic stroke were randomly
assigned to either WLT or CLT. WLT emphasized on a progressive, conventional
locomotor retraining practice (40 min) combined with the WALKBOT-assisted, haptic
guidance and random variable locomotor training (40 min) whereas CLT involved
conventional physical therapy alone (80 min). Both intervention dosages were
standardized and provided for 80 min, five days/week for four weeks. Clinical
outcomes included function ambulation category (FAC), Berg balance scale (BBS),
Korean modified Barthel index (K-MBI), modified Ashworth scale (MAS), and EuroQol
5 dimension (EQ-5D) before and after the four-week program as well as at follow
up four weeks after the intervention. Two-way repeated measure ANOVA showed
significant interaction effect (time * group) for FAC (p=0.02), BBS (p=0.03) ,
and K-MBI (p=0.00) across the pre-training, post-training, and follow-up tests,
indicating that WLT was more beneficial for balance, gait and daily activity
function than CLT alone. However, no significant difference in other variables
was observed. This is the first clinical trial that highlights the superior,
augmented effects of the WALKBOT-assisted locomotor training on balance, gait and
motor recovery when compared to the conventional locomotor training alone in
patients with hemiparetic stroke.
PMID- 25850090
TI - EEG-Based Attention Tracking During Distracted Driving.
AB - Distracted driving might lead to many catastrophic consequences. Developing a
countermeasure to track drivers' focus of attention (FOA) and engagement of
operators in dual (multi)-tasking conditions is thus imperative. Ten healthy
volunteers participated in a dual-task experiment that comprised two tasks: a
lane-keeping driving task and a mathematical problem-solving task (e.g.,
24+15=37?) during which their electroencephalogram (EEG) and behaviors were
concurrently recorded. Independent component analysis (ICA) was employed as a
spatial filter to separate the contributions of independent sources from the
recorded EEG data. The power spectra of six components (i.e., frontal, central,
parietal, occipital, left motor, and right motor) extracted from single-task
conditions were fed into support vector machine (SVM) based on the radial basis
function (RBF) kernel to build an FOA assessment system. The system achieved
84.6+/-5.8% and 86.2+/-5.4% classification accuracies in detecting the
participants' FOAs on the math versus driving tasks, respectively. This FOA
assessment system was then applied to evaluate participants' FOAs during dual
task conditions. The detected FOAs revealed that participants' cognitive
attention and strategies dynamically changed between tasks to optimize the
overall performance, as attention was limited and competed. The empirical results
of this study demonstrate the feasibility of a practical system to continuously
estimating cognitive attention through EEG spectra.
PMID- 25850092
TI - Distributed Signal Processing for Wireless EEG Sensor Networks.
AB - Inspired by ongoing evolutions in the field of wireless body area networks
(WBANs), this tutorial paper presents a conceptual and exploratory study of
wireless electroencephalography (EEG) sensor networks (WESNs), with an emphasis
on distributed signal processing aspects. A WESN is conceived as a modular
neuromonitoring platform for high-density EEG recordings, in which each node is
equipped with an electrode array, a signal processing unit, and facilities for
wireless communication. We first address the advantages of such a modular
approach, and we explain how distributed signal processing algorithms make WESNs
more power-efficient, in particular by avoiding data centralization. We provide
an overview of distributed signal processing algorithms that are potentially
applicable in WESNs, and for illustration purposes, we also provide a more
detailed case study of a distributed eye blink artifact removal algorithm.
Finally, we study the power efficiency of these distributed algorithms in
comparison to their centralized counterparts in which all the raw sensor signals
are centralized in a near-end or far-end fusion center.
PMID- 25850091
TI - The Retinal Response to Sinusoidal Electrical Stimulation.
AB - Rectangular electrical pulses are the primary stimulus waveform used in retinal
prosthetics as well as many other neural stimulation applications. Unfortunately,
the utility of pulsatile stimuli is limited by the inability to avoid the
activation of passing axons, which can result in the distortion of the spatial
patterns of elicited neural activity. Because avoiding axons would likely improve
clinical outcomes, the examination of alternate stimulus waveforms is warranted.
Here, we studied the response of rabbit retinal ganglion cells (RGCs) to
sinusoidal electrical stimulation applied at frequencies of 5, 10, 25, and 100
Hz. Targeted RGCs were restricted to 4 common types: OFF-Brisk Transient, OFF
Sustained, ON-Brisk Transient, and ON-Sustained. Interestingly, response patterns
varied between different types; the most notable difference was the relatively
weak response of ON-Sustained cells to low frequencies. Calculation of total
spike counts per trial revealed that lower frequencies are more charge efficient
than high frequencies. Finally, experiments utilizing synaptic blockers revealed
that 5 and 10 Hz activate photoreceptors while 25 and 100 Hz activate RGCs. Taken
together, our results suggest that while sinusoidal electrical stimulation may
provide a useful research tool, its clinical utility may be limited.
PMID- 25850093
TI - Further Results on Predictor-Based Control of Neuromuscular Electrical
Stimulation.
AB - Electromechanical delay (EMD) and uncertain nonlinear muscle dynamics can cause
destabilizing effects and performance loss during closed-loop control of
neuromuscular electrical stimulation (NMES). Linear control methods for NMES
often perform poorly due to these technical challenges. A new predictor-based
closed-loop controller called proportional integral derivative controller with
delay compensation (PID-DC) is presented in this paper. The PID-DC controller was
designed to compensate for EMDs during NMES. Further, the robust controller can
be implemented despite uncertainties or in the absence of model knowledge of the
nonlinear musculoskeletal dynamics. Lyapunov stability analysis was used to
synthesize the new controller. The effectiveness of the new controller was
validated and compared with two recently developed nonlinear NMES controllers,
through a series of closed-loop control experiments on four able-bodied human
subjects. Experimental results depict statistically significant improved
performance with PID-DC. The new controller is shown to be robust to variations
in an estimated EMD value.
PMID- 25850094
TI - Haptic Shared Control in Tele-Manipulation: Effects of Inaccuracies in Guidance
on Task Execution.
AB - Haptic shared control is a promising approach to improve tele-manipulated task
execution, by making safe and effective control actions tangible through guidance
forces. In current research, these guidance forces are most often generated based
on pre-generated, errorless models of the remote environment. Hence such guidance
forces are exempt from the inaccuracies that can be expected in practical
implementations. The goal of this research is to quantify the extent to which
task execution is degraded by inaccuracies in the model on which haptic guidance
forces are based. In a human-in-the-loop experiment, subjects (n = 14) performed
a realistic tele-manipulated assembly task in a virtual environment. Operators
were provided with various levels of haptic guidance, namely no haptic guidance
(conventional tele-manipulation), haptic guidance without inaccuracies, and
haptic guidance with translational inaccuracies (one large inaccuracy, in the
order of magnitude of the task, and a second smaller inaccuracy). The quality of
natural haptic feedback (i.e., haptic transparency) was varied between high and
low to identify the operator's ability to detect and cope with inaccuracies in
haptic guidance. The results indicate that haptic guidance is beneficial for task
execution when no inaccuracies are present in the guidance. When inaccuracies are
present, this may degrade task execution, depending on the magnitude and the
direction of the inaccuracy. The effect of inaccuracies on overall task
performance is dominated by effects found for the Constrained Translational
Movement, due to its potential for jamming. No evidence was found that a higher
quality of haptic transparency helps operators to detect and cope with
inaccuracies in the haptic guidance.
PMID- 25850095
TI - DietCam: Multiview Food Recognition Using a Multikernel SVM.
AB - Food recognition is a key component in evaluation of everyday food intakes, and
its challenge is due to intraclass variation. In this paper, we present an
automatic food classification method, DietCam, which specifically addresses the
variation of food appearances. DietCam consists of two major components,
ingredient detection and food classification. Food ingredients are detected
through a combination of a deformable part-based model and a texture verification
model. From the detected ingredients, food categories are classified using a
multiview multikernel SVM. In the experiment, DietCam presents reliability and
outperformance in recognition of food with complex ingredients on a database
including 15,262 food images of 55 food types.
PMID- 25850096
TI - CASDES: A Computer-Aided System to Support Dry Eye Diagnosis Based on Tear Film
Maps.
AB - Dry eye syndrome is recognized as a growing health problem, and one of the most
frequent reasons for seeking eye care. Its etiology and management challenge
clinicians and researchers alike, and several clinical tests can be used to
diagnose it. One of the most frequently used tests is the evaluation of the
interference patterns of the tear film lipid layer. Based on this clinical test,
this paper presents CASDES, a computer-aided system to support the diagnosis of
dry eye syndrome. Furthermore, CASDES is also useful to support the diagnosis of
other eye diseases, such as meibomian gland dysfunction, since it provides a tear
film map with highly useful information for eye practitioners. Experiments
demonstrate the robustness of this novel tool, which outperforms the previous
attempts to create tear film maps and provides reliable results in comparison
with the clinicians' annotations. Note that the processing time is noticeably
reduced with the proposed method, which will help to promote its clinical use in
the diagnosis and treatment of dry eye.
PMID- 25850097
TI - Validation of an Accelerometer to Quantify a Comprehensive Battery of Gait
Characteristics in Healthy Older Adults and Parkinson's Disease: Toward Clinical
and at Home Use.
AB - Measurement of gait is becoming important as a tool to identify disease and
disease progression, yet to date its application is limited largely to specialist
centers. Wearable devices enables gait to be measured in naturalistic
environments, however questions remain regarding validity. Previous research
suggests that when compared with a laboratory reference, measurement accuracy is
acceptable for mean but not variability or asymmetry gait characteristics. Some
fundamental reasons for this have been presented, (e.g., synchronization,
different sampling frequencies) but to date this has not been systematically
examined. The aims of this study were to: 1) quantify a comprehensive range of
gait characteristics measured using a single triaxial accelerometer-based
monitor; 2) examine outcomes and monitor performance in measuring gait in older
adults and those with Parkinson's disease (PD); and 3) carry out a detailed
comparison with those derived from an instrumented walkway to account for any
discrepancies. Fourteen gait characteristics were quantified in 30 people with
incident PD and 30 healthy age-matched controls. Of the 14 gait characteristics
compared, agreement between instruments was excellent for four (ICCs 0.913
0.983); moderate for four (ICCs 0.508-0.766); and poor for six characteristics
(ICCs 0.637-0.370). Further analysis revealed that differences reflect an
increased sensitivity of accelerometry to detect motion, rather than measurement
error. This is most likely because accelerometry measures gait as a continuous
activity rather than discrete footfall events, per instrumented tools. The
increased sensitivity shown for these characteristics will be of particular
interest to researchers keen to interpret "real-world" gait data. In conclusion,
use of a body-worn monitor is recommended for the measurement of gait but is
likely to yield more sensitive data for asymmetry and variability features.
PMID- 25850098
TI - Adaptive Neural Network Control of an Uncertain Robot With Full-State
Constraints.
AB - This paper studies the tracking control problem for an uncertain n -link robot
with full-state constraints. The rigid robotic manipulator is described as a
multiinput and multioutput system. Adaptive neural network (NN) control for the
robotic system with full-state constraints is designed. In the control design,
the adaptive NNs are adopted to handle system uncertainties and disturbances. The
Moore-Penrose inverse term is employed in order to prevent the violation of the
full-state constraints. A barrier Lyapunov function is used to guarantee the
uniform ultimate boundedness of the closed-loop system. The control performance
of the closed-loop system is guaranteed by appropriately choosing the design
parameters. Simulation studies are performed to illustrate the effectiveness of
the proposed control.
PMID- 25850099
TI - Filtering of Interval Type-2 Fuzzy Systems With Intermittent Measurements.
AB - In this paper, the problem of fuzzy filter design is investigated for a class of
nonlinear networked systems on the basis of the interval type-2 (IT2) fuzzy set
theory. In the design process, two vital factors, intermittent data packet
dropouts and quantization, are taken into consideration. The parameter
uncertainties are handled effectively by the IT2 membership functions determined
by lower and upper membership functions and relative weighting functions. A novel
fuzzy filter is designed to guarantee the error system to be stochastically
stable with Hinfinity performance. Moreover, the filter does not need to share
the same membership functions and number of fuzzy rules as those of the plant.
Finally, illustrative examples are provided to illustrate the effectiveness of
the method proposed in this paper.
PMID- 25850100
TI - On Configuration Trajectory Formation in Spatiotemporal Profile for Reproducing
Human Hand Reaching Movement.
AB - Most functional reaching activities in daily living generally require a hand to
reach the functional position in appropriate orientation with invariant
spatiotemporal profile. Effectively reproducing such spatiotemporal feature of
hand configuration trajectory in real time is essential to understand the human
motor control and plan human-like motion on anthropomorphic robotic arm. However,
there are no novel computational models in literature toward reproducing hand
configuration-to-configuration movement in spatiotemporal profile. In response to
the problem, this paper presents a computational framework for hand configuration
trajectory formation based on hierarchical principle of human motor control. The
composite potential field is constructed on special Euclidean Group to induce
time-varying configuration toward target. The dynamic behavior of hand is
described by a second-order kinematic model to produce the external
representation of high-level motor control. The multivariate regression relation
between intrinsic and extrinsic coordinates of arm, is statistically analyzed for
determining the arm orientation in real time, which produces the external
representation of low-level motor control. The proposed method is demonstrated in
an anthropomorphic arm by performing several highly curved self-reaching
movements. The generated configuration trajectories are compared with actual
human movement in spatiotemporal profile to validate the proposed method.
PMID- 25850101
TI - Relative Attribute SVM+ Learning for Age Estimation.
AB - When estimating age, human experts can provide privileged information that
encodes the facial attributes of aging, such as smoothness, face shape, face
acne, wrinkles, and bags under-eyes. In automatic age estimation, privileged
information is unavailable to test images. To overcome this problem, we
hypothesize that asymmetric information can be explored and exploited to improve
the generalizability of the trained model. Using the learning using privileged
information (LUPI) framework, we tested this hypothesis by carefully defining
relative attributes for support vector machine (SVM+) to improve the performance
of age estimation. We term this specific setting as relative attribute SVM+
(raSVM+), in which the privileged information enables separation of outliers from
inliers at the training stage and effectively manipulates slack variables and age
determination errors during model training, and thus guides the trained predictor
toward a generalizable solution. Experimentally, the superiority of raSVM+ was
confirmed by comparing it with state-of-the-art algorithms on the face and
gesture recognition research network (FG-NET) and craniofacial longitudinal
morphological face aging databases. raSVM+ is a promising development that
improves age estimation, with the mean absolute error reaching 4.07 on FG-NET.
PMID- 25850102
TI - Life Strain, Social Control, Social Learning, and Delinquency: The Effects of
Gender, Age, and Family SES Among Chinese Adolescents.
AB - Very few studies have examined the pathways to delinquency and causal factors for
demographic subgroups of adolescents in a different culture. This article
explores the effects of gender, age, and family socioeconomic status (SES) in an
integrated model of strain, social control, social learning, and delinquency
among a sample of Chinese adolescents. ANOVA is used to check for significant
differences between categories of demographic groups on the variables in the
integrated model, and the differential effects of causal factors in the
theoretical path models are examined. Further tests of interaction effects are
conducted to compare path coefficients between "high-risk" youths (i.e., male,
mid-teen, and low family SES adolescents) and other subgroups. The findings
identified similar pathways to delinquency across subgroups and clarified the
salience of causal factors for male, mid-teen, and low SES adolescents in a
different cultural context.
PMID- 25850103
TI - A Review of Questionnaire Measures for Assessing the Social Climate in Prisons
and Forensic Psychiatric Hospitals.
AB - Significant time and resources are devoted to the monitoring of social climate in
secure settings. However, if these efforts are to help (rather than hinder)
attempts to improve the functioning of such units, the monitoring of social
climate must be based on sound psychometric methods. The aim of this review was
to determine what questionnaires exist to measure the social climate in secure
settings and what evidence exists regarding their psychometric properties. Twelve
questionnaire-based measures of social climate were identified. The Essen Climate
Evaluation Schema has received the most consistent empirical support, but this
questionnaire does not provide as much of an in-depth, detailed insight into
social climate as that provided by other social climate questionnaires. Although
more extensive measures of climate exist, they have not yet received sufficient
validation to justify their routine use in practice. Nevertheless, there is
growing evidence that some questionnaire-based measures can provide a reliable
and valid assessment of the social climate in secure settings, which has
important clinical and theoretical implications.
PMID- 25850104
TI - Using Satellite-Based Spatiotemporal Resolved Air Temperature Exposure to Study
the Association between Ambient Air Temperature and Birth Outcomes in
Massachusetts.
AB - BACKGROUND: Studies looking at air temperature (Ta) and birth outcomes are rare.
OBJECTIVES: We investigated the association between birth outcomes and daily Ta
during various prenatal exposure periods in Massachusetts (USA) using both
traditional Ta stations and modeled addresses. METHODS: We evaluated birth
outcomes and average daily Ta during various prenatal exposure periods in
Massachusetts (USA) using both traditional Ta stations and modeled address Ta. We
used linear and logistic mixed models and accelerated failure time models to
estimate associations between Ta and the following outcomes among live births >
22 weeks: term birth weight (>= 37 weeks), low birth weight (LBW; < 2,500 g at
term), gestational age, and preterm delivery (PT; < 37 weeks). Models were
adjusted for individual-level socioeconomic status, traffic density, particulate
matter <= 2.5 MUm (PM2.5), random intercept for census tract, and mother's
health. RESULTS: Predicted Ta during multiple time windows before birth was
negatively associated with birth weight: Average birth weight was 16.7 g lower
(95% CI: -29.7, -3.7) in association with an interquartile range increase (8.4
degrees C) in Ta during the last trimester. Ta over the entire pregnancy was
positively associated with PT [odds ratio (OR) = 1.02; 95% CI: 1.00, 1.05] and
LBW (OR = 1.04; 95% CI: 0.96, 1.13). CONCLUSIONS: Ta during pregnancy was
associated with lower birth weight and shorter gestational age in our study
population.
PMID- 25850105
TI - The effect of geography and citizen behavior on motor vehicle deaths in the
United States.
AB - Death due to motor vehicle collisions (MVCs) remains a leading cause of death in
the US and alcohol plays a prominent role in a large proportion of these
fatalities nationwide. Rates for these incidents vary widely among states and
over time. Here, we explore the extent to which driving volume, alcohol
consumption, legislation, political ideology, and geographical factors influence
MVC deaths across states and time. We specify structural equation models for
extracting associations between the factors and outcomes for MVC deaths and
compute correlation functions of states' relative geographic and political
positions to elucidate the relative contribution of these factors. We find
evidence that state-level variation in MVC deaths is associated with time-varying
driving volume, alcohol consumption, and legislation. These relationships are
modulated by state spatial proximity, whereby neighboring states are found to
share similar MVC death rates over the thirty-year observation period. These
results support the hypothesis that neighboring states exhibit similar risk and
protective characteristics, despite differences in political ideology.
PMID- 25850106
TI - Prenatal Phthalate Exposure and Childhood Growth and Blood Pressure: Evidence
from the Spanish INMA-Sabadell Birth Cohort Study.
AB - BACKGROUND: Human evidence on the effects of early life phthalate exposure on
obesity and cardiovascular disease risks, reported by experimental studies, is
limited to a few cross-sectional studies. OBJECTIVES: We evaluated the
associations between prenatal phthalate exposure and childhood growth and blood
pressure in a Spanish birth cohort study. METHODS: We assessed exposure using the
average of two phthalate metabolite spot-urine concentrations collected from the
mothers in the first and third pregnancy trimesters (creatinine-adjusted, n =
391). Study outcomes were the difference in age- and sex-specific z-scores for
weight between birth and 6 months of age; and repeated age- and sex-specific z
scores for body mass index (BMI) at 1, 4, and 7 years; waist-to-height ratio at 4
and 7 years; and age- and height-specific z-scores for systolic and diastolic
blood pressure at 4 and 7 years. RESULTS: The sum of five high-molecular-weight
phthalate metabolites (SigmaHMWPm) was associated with lower weight z-score
difference between birth and 6 months (beta per doubling of exposure = -0.41; 95%
CI: -0.75, -0.06) and BMI z-scores at later ages in boys (beta = -0.28; 95% CI:
0.60, 0.03) and with higher weight z-score difference (beta = 0.24; 95% CI:
0.16, 0.65) and BMI z-scores in girls (beta = 0.30; 95% CI: -0.04, 0.64) (p for
sex interaction = 0.01 and 0.05, respectively). The sum of three low-molecular
weight phthalates (SigmaLMWPm) was not significantly associated with any of the
growth outcomes. SigmaHMWPm and SigmaLMWPm were associated with lower systolic
blood pressure z-scores in girls but not in boys. CONCLUSIONS: This study
suggests that prenatal phthalate exposure may be associated with postnatal growth
and blood pressure in a sex-specific manner. Inconsistencies with previous cross
sectional findings highlight the necessity for evaluating phthalate health
effects in prospective studies.
PMID- 25850108
TI - Gold Nanorod-pNIPAM Hybrids with Reversible Plasmon Coupling: Synthesis,
Modeling, and SERS Properties.
AB - The thermoresponsive optical properties of Au nanorod-doped poly(N
isopropylacrylamide) (Au NR-pNIPAM) microgels with different Au NR payloads and
aspect ratios are presented. Since the volume phase transition of pure pNIPAM
microgels is reversible, the optical response reversibility of Au NR-pNIPAM
hybrids is systematically analyzed. Besides, extinction cross-section and near
field enhancement simulations for Au NR-microgel hybrids are performed using a
new numerical method based on the surface integral equation method of moments
formulation (M3 solver). Additionally, the Au NR-microgel hybrid systems are
expected to serve as excellent broadband surface-enhanced Raman scattering (SERS)
substrates due to the temperature-controlled formation of hot spots and the
tunable optical properties. The optical enhancing properties related to SERS are
tested with three laser lines, evidencing excitation wavelength-dependent
efficiency that can be easily controlled by either the aspect ratio
(length/width) of the assembled Au NR or by the Au NR payload per microgel.
Finally, the SERS efficiency of the prepared Au NR-pNIPAM hybrids is found to be
stable for months.
PMID- 25850107
TI - Transdermal Uptake of Diethyl Phthalate and Di(n-butyl) Phthalate Directly from
Air: Experimental Verification.
AB - BACKGROUND: Fundamental considerations indicate that, for certain phthalate
esters, dermal absorption from air is an uptake pathway that is comparable to or
greater than inhalation. Yet this pathway has not been experimentally evaluated
and has been largely overlooked when assessing uptake of phthalate esters.
OBJECTIVES: This study investigated transdermal uptake, directly from air, of
diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans. METHODS: In a
series of experiments, six human participants were exposed for 6 hr in a chamber
containing deliberately elevated air concentrations of DEP and DnBP. The
participants either wore a hood and breathed air with phthalate concentrations
substantially below those in the chamber or did not wear a hood and breathed
chamber air. All urinations were collected from initiation of exposure until 54
hr later. Metabolites of DEP and DnBP were measured in these samples and
extrapolated to parent phthalate intakes, corrected for background and hood air
exposures. RESULTS: For DEP, the median dermal uptake directly from air was 4.0
MUg/(MUg/m(3) in air) compared with an inhalation intake of 3.8 MUg/(MUg/m(3) in
air). For DnBP, the median dermal uptake from air was 3.1 MUg/(MUg/m(3) in air)
compared with an inhalation intake of 3.9 MUg/(MUg/m(3) in air). CONCLUSIONS:
This study shows that dermal uptake directly from air can be a meaningful
exposure pathway for DEP and DnBP. For other semivolatile organic compounds
(SVOCs) whose molecular weight and lipid/air partition coefficient are in the
appropriate range, direct absorption from air is also anticipated to be
significant.
PMID- 25850109
TI - An estimation of finger-tapping rates and load capacities and the effects of
various factors.
AB - OBJECTIVE: The aim of this study was to estimate the finger-tapping rates and
finger load capacities of eight fingers (excluding thumbs) for a healthy adult
population and investigate the effects of various factors on tapping rate.
BACKGROUND: Finger-tapping rate, the total number of finger taps per unit of
time, can be used as a design parameter of various products and also as a
psychomotor test for evaluating patients with neurologic problems. METHOD: A 1
min tapping task was performed by 148 participants with maximum volitional tempo
for each of eight fingers. For each of the tapping tasks, the participant with
the corresponding finger tapped the associated key in the standard position on
the home row of a conventional keyboard for touch typing. RESULTS: The index and
middle fingers were the fastest fingers for both hands, and little fingers the
slowest. All dominant-hand fingers, except little finger, had higher tapping
rates than the fastest finger of the nondominant hand. Tapping rate decreased
with age and smokers tapped faster than nonsmokers. Tapping duration and exercise
had also significant effect on tapping rate. CONCLUSION: Normative data of
tapping rates and load capacities of eight fingers were estimated for the adult
population. In designs of psychomotor tests that require the use of tapping rate
or finger load capacity data, the effects of finger, age, smoking, and tapping
duration need to be taken into account. APPLICATION: The findings can be used for
ergonomic designs requiring finger-tapping capacity and also as a reference in
psychomotor tests.
PMID- 25850110
TI - Clutter in electronic medical records: examining its performance and attentional
costs using eye tracking.
AB - OBJECTIVE: The objective was to use eye tracking to trace the underlying changes
in attention allocation associated with the performance effects of clutter,
stress, and task difficulty in visual search and noticing tasks. BACKGROUND:
Clutter can degrade performance in complex domains, yet more needs to be known
about the associated changes in attention allocation, particularly in the
presence of stress and for different tasks. Frequently used and relatively simple
eye tracking metrics do not effectively capture the various effects of clutter,
which is critical for comprehensively analyzing clutter and developing targeted,
real-time countermeasures. METHOD: Electronic medical records (EMRs) were chosen
as the application domain for this research. Clutter, stress, and task difficulty
were manipulated, and physicians' performance on search and noticing tasks was
recorded. Several eye tracking metrics were used to trace attention allocation
throughout those tasks, and subjective data were gathered via a debriefing
questionnaire. RESULTS: Clutter degraded performance in terms of response time
and noticing accuracy. These decrements were largely accentuated by high stress
and task difficulty. Eye tracking revealed the underlying attentional mechanisms,
and several display-independent metrics were shown to be significant indicators
of the effects of clutter. CONCLUSION: Eye tracking provides a promising means to
understand in detail (offline) and prevent (in real time) major performance
breakdowns due to clutter. APPLICATION: Display designers need to be aware of the
risks of clutter in EMRs and other complex displays and can use the identified
eye tracking metrics to evaluate and/or adjust their display.
PMID- 25850111
TI - Using Modeling and Simulation to Predict Operator Performance and Automation
Induced Complacency With Robotic Automation: A Case Study and Empirical
Validation.
AB - OBJECTIVE: The aim of this study was to develop and validate a computational
model of the automation complacency effect, as operators work on a robotic arm
task, supported by three different degrees of automation. BACKGROUND: Some
computational models of complacency in human-automation interaction exist, but
those are formed and validated within the context of fairly simplified monitoring
failures. This research extends model validation to a much more complex task, so
that system designers can establish, without need for human-in-the-loop (HITL)
experimentation, merits and shortcomings of different automation degrees. METHOD:
We developed a realistic simulation of a space-based robotic arm task that could
be carried out with three different levels of trajectory visualization and
execution automation support. Using this simulation, we performed HITL testing.
Complacency was induced via several trials of correctly performing automation and
then was assessed on trials when automation failed. Following a cognitive task
analysis of the robotic arm operation, we developed a multicomponent model of the
robotic operator and his or her reliance on automation, based in part on visual
scanning. RESULTS: The comparison of model predictions with empirical results
revealed that the model accurately predicted routine performance and predicted
the responses to these failures after complacency developed. However, the
scanning models do not account for the entire attention allocation effects of
complacency. APPLICATIONS: Complacency modeling can provide a useful tool for
predicting the effects of different types of imperfect automation. The results
from this research suggest that focus should be given to supporting situation
awareness in automation development.
PMID- 25850112
TI - Visual Performance With Small Concave and Convex Displays.
AB - OBJECTIVE: In this study, we aim to investigate how users' visual performance
with a small flexible display changes based on the direction (i.e., convex,
concave) and the magnitude (i.e., low, high) of the display curvature.
BACKGROUND: Despite the wide interest in flexible display materials and
deformable displays, the potential effects of nonplanar display surfaces on human
perception and performance have received little attention. This study is the
first to demonstrate how curving affects visual performance with an actual
flexible display (4.5-in. active-matrix organic light-emitting diode). METHOD: In
a series of three experiments, we compared the performance with a planar display
to the performance with concave and convex display surfaces with low and high
curvature magnitudes. Two visual search tasks were employed that required the
subject to detect target letters based on their contrast (Experiments 1 and 2)
and identity (Experiment 3). Performance was measured as the sensitivity of
target detection (d') and threshold time of the search, respectively. RESULTS:
There were similar sensitivities for targets across the curvature variants, but
the high-magnitude curvatures resulted in prolonged search times, especially for
the convex form. In both of the tasks, performance was dependent on the display
location, which was defined as the target's distance from the display center.
CONCLUSION: High curvature magnitudes should be avoided, even in small displays,
because large local changes in visual stimuli decrease processing speed outside
the central display. APPLICATION: The findings have implications for the
development of technologies, applications, and user interfaces for flexible
displays and the design of visual display devices.
PMID- 25850114
TI - The Impact of Sleep Disruption on Complex Cognitive Tasks: A Meta-Analysis.
AB - OBJECTIVE: We aimed to build upon the state of knowledge about the impacts of
sleep disruption into the domain of complex cognitive task performance for three
types of sleep disruption: total sleep deprivation, sleep restriction, and
circadian cycle. BACKGROUND: Sleep disruption affects human performance by
increasing the likelihood of errors or the time it takes to complete tasks, such
as the Psychomotor Vigilance Task. It is not clear whether complex tasks are
affected in the same way. Understanding the impact of sleep disruption on complex
cognitive tasks is important for, and in some instances more relevant to,
professional workers confronted with unexpected, catastrophic failures following
a period of disrupted sleep. METHOD: Meta-analytic review methods were applied to
each of the three different areas of sleep disruption research. RESULTS: Complex
cognitive task performance declines over consecutive hours of continuous
wakefulness as well as consecutive days of restricted sleep, is worse for
severely restricted sleep (4 or fewer hours in bed), is worse during the
circadian nadir than apex, and appears less degraded than simple task
performance. CONCLUSION: The reviews suggest that complex cognitive task
performance may not be impacted by disrupted sleep as severely as simple
cognitive task performance. APPLICATION: Findings apply to predicting effects of
sleep disruption on workers in safety-critical environments, such as health care,
aviation, the military, process control, and in particular, safety-critical
environments involving shiftwork or long-duration missions.
PMID- 25850113
TI - Asynchronous Brainstorming in an Industrial Setting: Exploratory Studies.
AB - OBJECTIVE: The goal of this study was to examine the effectiveness of
brainwriting in an industrial setting. BACKGROUND: Research has demonstrated that
group interaction can inhibit idea generation. Written exchanges of ideas in
groups have been found to be an effective way to increase idea generation. To our
knowledge, no study has examined the potential of brainwriting for group idea
generation in work settings or the impact of different sequences of group and
individual idea generation. METHOD: Participants in a high-technology company
participated in two brainwriting studies. In one study, participants generated
ideas either first alone and then in a group or in the reverse order. In a second
study, participants either generated as a group during the entire session or
alternated individual ideation with a periodic review of the group's ideas.
RESULTS: In the first study, participants who generated ideas first as a group
and then as individuals performed best. In the first session, group writing also
tended to lead to more ideas than did individual writing. In the second study,
participants with periodic reviews performed best. CONCLUSION: The results
suggest that alternation in individual and group brainwriting can enhance the
number of ideas generated. The group-to-alone sequence is also beneficial since
it allows group members to build on shared ideas. APPLICATION: This research
indicates that collaborative idea sessions can be beneficial in work sessions if
the brainwriting paradigm is used with an appropriate alternation of group
ideation or review sessions with individual idea generation sessions.
PMID- 25850115
TI - Effects of Stereoscopic Depth on Vigilance Performance and Cerebral Hemodynamics.
AB - OBJECTIVE: We tested the possibility that monitoring a display wherein critical
signals for detection were defined by a stereoscopic three-dimensional (3-D)
image might be more resistant to the vigilance decrement, and to temporal
declines in cerebral blood flow velocity (CBFV), than monitoring a display
featuring a customary two-dimensional (2-D) image. BACKGROUND: Hancock has
asserted that vigilance studies typically employ stimuli for detection that do
not exemplify those that occur in the natural world. As a result, human
performance is suboptimal. From this perspective, tasks that better approximate
perception in natural environments should enhance performance efficiency. To test
that possibility, we made use of stereopsis, an important means by which
observers interact with their everyday surroundings. METHOD: Observers monitored
a circular display in which a vertical line was embedded. Critical signals for
detection in a 2-D condition were instances in which the line was rotated
clockwise from vertical. In a 3-D condition, critical signals were cases in which
the line appeared to move outward toward the observer. RESULTS: The overall level
of signal detection and the stability of detection over time were greater when
observers monitored for 3-D changes in target depth compared to 2-D changes in
target orientation. However, the 3-D display did not retard the temporal decline
in CBFV. CONCLUSION: These results provide the initial demonstration that 3-D
displays can enhance performance in vigilance tasks. APPLICATION: The use of 3-D
displays may be productive in augmenting system reliability when operator
vigilance is vital.
PMID- 25850116
TI - Smartphone Text Input Method Performance, Usability, and Preference With Younger
and Older Adults.
AB - OBJECTIVE: User performance, perceived usability, and preference for five
smartphone text input methods were compared with younger and older novice adults.
BACKGROUND: Smartphones are used for a variety of functions other than phone
calls, including text messaging, e-mail, and web browsing. Research comparing
performance with methods of text input on smartphones reveals a high degree of
variability in reported measures, procedures, and results. This study reports on
a direct comparison of five of the most common input methods among a population
of younger and older adults, who had no experience with any of the methods.
METHOD: Fifty adults (25 younger, 18-35 years; 25 older, 60-84 years) completed a
text entry task using five text input methods (physical Qwerty, onscreen Qwerty,
tracing, handwriting, and voice). Entry and error rates, perceived usability, and
preference were recorded. RESULTS: Both age groups input text equally fast using
voice input, but older adults were slower than younger adults using all other
methods. Both age groups had low error rates when using physical Qwerty and
voice, but older adults committed more errors with the other three methods. Both
younger and older adults preferred voice and physical Qwerty input to the
remaining methods. Handwriting consistently performed the worst and was rated
lowest by both groups. CONCLUSION: Voice and physical Qwerty input methods proved
to be the most effective for both younger and older adults, and handwriting input
was the least effective overall. APPLICATION: These findings have implications to
the design of future smartphone text input methods and devices, particularly for
older adults.
PMID- 25850117
TI - Comparison of Two Watch Schedules for Personnel at the White House Military
Office President's Emergency Operations Center.
AB - OBJECTIVE: The aim of this study was to assess effectiveness of an alternative,
24-hr-on/72-hr-off watchstanding schedule on sleep and morale of personnel
assigned to the President's Emergency Operations Center (PEOC). BACKGROUND: As
part of the White House Military Office, PEOC personnel historically worked a 12
hr "Panama" watch schedule. Personnel reported experiencing chronic insufficient
and disrupted sleep patterns and sought advice for improving their watchstanding
schedule. METHOD: Participants (N = 14 active-duty military members, ages 29 to
42 years) completed the Profile of Mood State (POMS) three times: before, during,
and after switching to the alternative schedule with 5-hr sleep periods built
into their workday. Participants completed a poststudy questionnaire to assess
individual schedule preferences. Sleep was measured actigraphically, supplemented
by activity logs. RESULTS: As indicated by POMS scores, mood improved
significantly on the new schedule. Although average total sleep amount did not
change substantively, the timing of sleep was more consistent on the new
schedule, resulting in better sleep hygiene. PEOC personnel overwhelmingly
preferred the new schedule, reporting not only that they felt more rested but
that the new schedule was more conducive to the demands of family life.
CONCLUSIONS: Demands of family life and time spent commuting were found to be
critical factors for acceptance of the alternative schedule. This new schedule
will be most effective if personnel adhere to the scheduled rest periods assigned
during their 24-hr duty. APPLICATION: A successful schedule should avoid
conflicts between social life and operational demands. Results may lead to
changes in the work schedules of other departments with similar 24/7
responsibilities.
PMID- 25850118
TI - Usability and Safety in Electronic Medical Records Interface Design: A Review of
Recent Literature and Guideline Formulation.
AB - OBJECTIVE: The objectives of this study were to (a) review electronic medical
record (EMR) and related electronic health record (EHR) interface usability
issues, (b) review how EMRs have been evaluated with safety analysis techniques
along with any hazard recognition, and (c) formulate design guidelines and a
concept for enhanced EMR interfaces with a focus on diagnosis and documentation
processes. BACKGROUND: A major impact of information technology in health care
has been the introduction of EMRs. Although numerous studies indicate use of EMRs
to increase health care quality, there remain concerns with usability issues and
safety. METHOD: A literature search was conducted using Compendex, PubMed,
CINAHL, and Web of Science databases to find EMR research published since 2000.
Inclusion criteria included relevant English-language papers with subsets of
keywords and any studies (manually) identified with a focus on EMR usability.
RESULTS: Fifty studies met the inclusion criteria. Results revealed EMR and EHR
usability problems to include violations of natural dialog, control consistency,
effective use of language, effective information presentation, and customization
principles as well as a lack of error prevention, minimization of cognitive load,
and feedback. Studies focusing on EMR system safety made no objective assessments
and applied only inductive reasoning methods for hazard recognition. CONCLUSION:
On the basis of the identified usability problems and structure of safety
analysis techniques, we provide EMR design guidelines and a design concept
focused on the diagnosis process and documentation. APPLICATION: The design
guidelines and new interface concept can be used for prototyping and testing
enhanced EMRs.
PMID- 25850119
TI - America's medical school: 5,000 graduates since the "first class".
AB - In 1980, the Uniformed Services University of the Health Sciences (USU) graduated
its first class of medical students. As a national university intended to produce
"career-committed" military officers and future leaders of the Military Health
System, USU functions as the service academy for military medicine and public
health. More than 40 years after the school's charter and 5,000 graduates since
the first class, we describe the original purpose of USU and provide an update on
its achievements. In particular, we address the question of the "staying power"
of the University's alumni-the degree to which graduation from the nation's
military medical school is associated with long years of devoted service to
military medicine. At a time when the MHS is confronting the challenge of
extended deployments, rising health care costs, and a growing array of threats to
our nation's health, we suggest that America needs USU now more than ever.
PMID- 25850120
TI - Does the MCAT predict medical school and PGY-1 performance?
AB - BACKGROUND: The Medical College Admissions Test (MCAT) is a high-stakes test
required for entry to most U. S. medical schools; admissions committees use this
test to predict future accomplishment. Although there is evidence that the MCAT
predicts success on multiple choice-based assessments, there is little
information on whether the MCAT predicts clinical-based assessments of
undergraduate and graduate medical education performance. This study looked at
associations between the MCAT and medical school grade point average (GPA),
Medical Licensing Examination (USMLE) scores, observed patient care encounters,
and residency performance assessments. METHODS: This study used data collected as
part of the Long-Term Career Outcome Study to determine associations between MCAT
scores, USMLE Step 1, Step 2 clinical knowledge and clinical skill, and Step 3
scores, Objective Structured Clinical Examination performance, medical school
GPA, and PGY-1 program director (PD) assessment of physician performance for
students graduating 2010 and 2011. RESULTS: MCAT data were available for all
students, and the PGY PD evaluation response rate was 86.2% (N = 340). All
permutations of MCAT scores (first, last, highest, average) were weakly
associated with GPA, Step 2 clinical knowledge scores, and Step 3 scores. MCAT
scores were weakly to moderately associated with Step 1 scores. MCAT scores were
not significantly associated with Step 2 clinical skills Integrated Clinical
Encounter and Communication and Interpersonal Skills subscores, Objective
Structured Clinical Examination performance or PGY-1 PD evaluations. DISCUSSION:
MCAT scores were weakly to moderately associated with assessments that rely on
multiple choice testing. The association is somewhat stronger for assessments
occurring earlier in medical school, such as USMLE Step 1. The MCAT was not able
to predict assessments relying on direct clinical observation, nor was it able to
predict PD assessment of PGY-1 performance.
PMID- 25850121
TI - Predicting medical school and internship success: does the quality of the
research and clinical experience matter?
AB - OBJECTIVES: This article explores specific aspects of self-reported clinical and
research experience and their relationship to performance in medical training.
METHODS: This is a retrospective cohort study conducted at the Uniformed Services
University. The American Medical College Application Service application was used
to discern students' self-reported clinical and research experience. Two authors
applied a classification scheme for clinical and research experience to the self
reported experiences. Study outcomes included medical school grade point average
(GPA), U.S. Medical Licensing Examination (USMLE) scores, and intern expertise
and professionalism scores. A linear regression analysis was conducted for each
outcome while controlling for prematriculation GPA. RESULTS: Data were retrieved
on 1,020 matriculants. There were several statistically significant but small
differences across outcomes when comparing the various categories of clinical
experience with no clinical experience. The technician-level experience group had
a decrease of 0.1 in cumulative GPA in comparison to students without self
reported clinical experience (p = 0.004). This group also performed 5 points
lower on the USMLE Step 2 than students who did not report clinical experience (p
= 0.013). The various levels of self-reported research experience were unrelated
to success in medical school and graduate medical education. DISCUSSION: These
findings indicate that self-reported technician-level clinical experience is
related to a small reduction in typically reported outcomes in medical school.
PMID- 25850122
TI - Are commonly used premedical school or medical school measures associated with
board certification?
AB - PURPOSE: To determine if there is an association between several commonly
obtained premedical school and medical school measures and board certification
performance. We specifically included measures from our institution for which we
have predictive validity evidence into the internship year. We hypothesized that
board certification would be most likely to be associated with clinical measures
of performance during medical school, and with scores on standardized tests,
whether before or during medical school. METHODS: Achieving board certification
in an American Board of Medical Specialties specialty was used as our outcome
measure for a 7-year cohort of graduates (1995-2002). Age at matriculation,
Medical College Admissions Test (MCAT) score, undergraduate college grade point
average (GPA), undergraduate college science GPA, Uniformed Services University
(USU) cumulative GPA, USU preclerkship GPA, USU clerkship year GPA, departmental
competency committee evaluation, Internal Medicine (IM) clerkship clinical
performance rating (points), IM total clerkship points, history of Student
Promotion Committee review, and United States Medical Licensing Examination
(USMLE) Step 1 score and USMLE Step 2 clinical knowledge score were associated
with this outcome. RESULTS: Ninety-three of 1,155 graduates were not certified,
resulting in an average rate of board certification of 91.9% for the study
cohort. Significant small correlations were found between board certification and
IM clerkship points (r = 0.117), IM clerkship grade (r = 0.108), clerkship year
GPA (r = 0.078), undergraduate college science GPA (r = 0.072), preclerkship GPA
and medical school GPA (r = 0.068 for both), USMLE Step 1 (r = 0.066),
undergraduate college total GPA (r = 0.062), and age at matriculation (r =
0.061). In comparing the two groups (board certified and not board certified
cohorts), significant differences were seen for all included variables with the
exception of MCAT and USMLE Step 2 clinical knowledge scores. All the variables
put together could explain 4.1% of the variance of board certification by
logistic regression. CONCLUSIONS: This investigation provides some additional
validity evidence that measures collected for purposes of student evaluation
before and during medical school are warranted.
PMID- 25850123
TI - Longitudinal effects of medical students' communication skills on future
performance.
AB - BACKGROUND: The Essential Elements of Communication (EEC) were developed from the
Kalamazoo consensus statement on physician-patient communication. The Uniformed
Services University of the Health Sciences (USU) has adopted a longitudinal
curriculum to use the EEC both as a learning tool during standardized patient
encounters and as an evaluation tool culminating with the end of preclerkship
objective-structured clinical examinations (OSCE). Medical educators have
recently emphasized the importance of teaching communication skills, as evidenced
by the United States Medical Licensing Examination testing both the integrated
clinical encounter (ICE) and communication and interpersonal skills (CIS) within
the Step 2 Clinical Skills exam (CS). PURPOSE: To determine the associations
between students' EEC OSCE performance at the end of the preclerkship period with
later communication skills assessment and evaluation outcomes in the context of a
longitudinal curriculum spanning both undergraduate medical education and
graduate medical education. METHODS: Retrospective data from preclerkship
(overall OSCE scores and EEC OSCE scores) and clerkship outcomes (internal
medicine [IM] clinical points and average clerkship National Board of Medical
Examiners [NBME] scores) were collected from 167 USU medical students from the
class of 2011 and compared to individual scores on the CIS and ICE components of
Step 2 CS, as well as to the communication skills component of the program
directors' evaluation of trainees during their postgraduate year 1 (PGY-1)
residency. In addition to bivariate Pearson correlation analysis, we conducted
multiple linear regression analysis to examine the predictive power of the EEC
score beyond the IM clerkship clinical points and the average NBME Subject Exams
score on the outcome measures. RESULTS: The EEC score was a significant predictor
of the CIS score and the PGY-1 communication skills score. Beyond the average
NBME Subject Exams score and the IM clerkship clinical points, the EEC score
explained an additional 13% of the variance in the Step 2 CIS score and an
additional 6% of the variance in the PGY-1 communication skills score. In
addition, the EEC score was more closely associated with the CIS score than the
ICE score. CONCLUSION: The use of a standardized approach with a communication
tool like the EEC can help explain future performance in communication skills
independent of other education outcomes. In the context of a longitudinal
curriculum, this information may better inform medical educators on learners'
communication capabilities and more accurately direct future remediation efforts.
PMID- 25850124
TI - Assessing task importance and anxiety in medical school: an instrument
development and initial validation study.
AB - Recent research in medical education suggests that students' motivational
beliefs, such as their beliefs about the importance of a task, and their emotions
are meaningful predictors of learning and performance. The primary purpose of
this study was to develop a self-report measure of "task importance" and
"anxiety" in relation to several medical education competencies and to collect
validity evidence for the new measures. The secondary purpose was to evaluate
differences in these measures by year of medical school. Exploratory factor
analysis of scores from 368 medical school students suggested two task importance
factors and three anxiety factors. The task importance and anxiety subscales were
weakly related to each other and exhibited consistently negative and positive
correlations, respectively, with three self-efficacy subscales. The task
importance subscales were positively related to "metacognition," whereas
"interpersonal skills anxiety" and "health knowledge anxiety" were positively
related to "procrastination." All three anxiety factors were positively related
to "avoidance of help seeking," whereas "interpersonal skills and professionalism
importance" was negatively related to help avoidance behaviors. Finally,
comparisons across the 4 years of medical school indicated that some aspects of
task importance and anxiety varied significantly. Overall, findings from this
study provide validity evidence for the psychometric quality of these scales,
which capture task importance and anxiety in medical students. Limitations and
implications for medical education research are discussed.
PMID- 25850125
TI - Preclerkship assessment of clinical skills and clinical reasoning: the
longitudinal impact on student performance.
AB - PURPOSE: Many medical schools across the United States are undergoing curriculum
reform designed, in part, to integrate basic sciences and clinical skills.
Evidence has suggested that preclerkship courses in clinical skills and clinical
reasoning are predictive of student performance on the clerkship. We hypothesized
that a combination of outcome measures from preclerkship clinical skills and
clinical reasoning courses (Objective Structured Clinical Examination scores,
preceptor evaluations, National Board of Medical Examiners subject examination
scores, and small group participation grades) would be correlated to performance
in internship (program director [PD]evaluation form at end of first postgraduate
year). METHODS: Outcome measures from preclerkship clinical skills and clinical
reasoning courses and PD evaluation forms from 514 medical students graduating
between 2009 and 2011 were analyzed in a multiple linear regression model.
RESULTS: Preclerkship clinical skills and clinical reasoning outcome measures
were significant contributors to the linear regression model and were able to
explain 13.9% of the variance in expertise and 7.6% of the variance in
professionalism as measured by the PD evaluation form. CONCLUSION: Clinical
skills and clinical reasoning courses during the preclerkship period explained a
significant amount of performance at the graduate medical education level. Our
data suggest that these courses provide valuable information regarding student
abilities in internship. Early recognition of struggling students may provide an
opportunity to break a cycle of poor performance that can persist into residency
training.
PMID- 25850126
TI - The association of students requiring remediation in the internal medicine
clerkship with poor performance during internship.
AB - PURPOSE: To determine whether the Uniformed Services University (USU) system of
workplace performance assessment for students in the internal medicine clerkship
at the USU continues to be a sensitive predictor of subsequent poor performance
during internship, when compared with assessments in other USU third year
clerkships. METHOD: Utilizing Program Director survey results from 2007 through
2011 and U.S. Medical Licensing Examination (USMLE) Step 3 examination results as
the outcomes of interest, we compared performance during internship for students
who had less than passing performance in the internal medicine clerkship and
required remediation, against students whose performance in the internal medicine
clerkship was successful. We further analyzed internship ratings for students who
received less than passing grades during the same time period on other third year
clerkships such as general surgery, pediatrics, obstetrics and gynecology, family
medicine, and psychiatry to evaluate whether poor performance on other individual
clerkships were associated with future poor performance at the internship level.
Results for this recent cohort of graduates were compared with previously
published findings. RESULTS: The overall survey response rate for this 5 year
cohort was 81% (689/853). Students who received a less than passing grade in the
internal medicine clerkship and required further remediation were 4.5 times more
likely to be given poor ratings in the domain of medical expertise and 18.7 times
more likely to demonstrate poor professionalism during internship. Further,
students requiring internal medicine remediation were 8.5 times more likely to
fail USMLE Step 3. No other individual clerkship showed any statistically
significant associations with performance at the intern level. On the other hand,
40% of students who successfully remediated and did graduate were not identified
during internship as having poor performance. CONCLUSIONS: Unsuccessful clinical
performance which requires remediation in the third year internal medicine
clerkship at Uniformed Services University of the Health Sciences continues to be
strongly associated with poor performance at the internship level. No significant
associations existed between any of the other clerkships and poor performance
during internship and Step 3 failure. The strength of this association with the
internal medicine clerkship is most likely because of an increased level of
sensitivity in detecting poor performance.
PMID- 25850128
TI - Medical student attitudes toward the medically underserved: the USU perspective.
AB - This study examined a cohort of students attending the Uniformed Services
University regarding their attitudes toward medical care in underserved
populations. Using the previously validated Medical Student Attitudes Toward the
Underserved (MSATU), repeated measures analysis of variance showed that student
attitudes toward care in underserved populations was less favorable than limited
national data at entry and declined over time (Mean MSATU total score Year 1:
46.2 [SD 10.95]; Year 4: 41.7 [SD 12.3] p < 0.01). Differences in medical school
debt, exposure to underserved populations, and the definition of "service" in the
context of active duty military status might explain some of our findings.
Providing broad service learning opportunities within the curriculum could
increase student exposure to underserved populations and strengthen the social
contract between community and institution.
PMID- 25850127
TI - The clinical integrative puzzle for teaching and assessing clinical reasoning:
preliminary feasibility, reliability, and validity evidence.
AB - BACKGROUND: Expertise in clinical reasoning is essential for high-quality patient
care. The Clinical Integrative Puzzle (CIP) is a novel assessment method for
clinical reasoning. The purpose of our study was to further describe the CIP,
providing feasibility, reliability, and validity evidence to support this tool
for teaching and evaluating clinical reasoning. METHODS: We conducted a
prospective, randomized crossover trial assessing the CIP in second-year medical
students from a single institution. Feasibility was estimated through the time
taken to complete a CIP during a CIP session and through comments from faculty
developers. Reliability was addressed through calculating odd-even item
reliability (split-half procedure) for grid questions within each CIP. Evidence
for content, concurrent, and predictive validity was also measured. RESULTS: 36
students participated in the study. Data suggested successful randomization of
participants and nonparticipants. The CIP was found to have high feasibility,
acceptable reliability (0.43-0.73 with a mean of 0.60) with a short time for CIP
completion. Spearman-Brown correction estimated a reliability of 0.75 with
completing two grids (estimated time of 50 minutes) and 0.82 for three grids
(estimated time of 75 minutes). Validity evidence was modest; the CIP is
consistent with clinical reasoning literature and the CIP modestly correlated
with small group performance (r = 0.3, p < 0.05). CONCLUSIONS: Assessing clinical
reasoning in medical students is challenging. Our data provide good feasibility
and reliability evidence for the use of CIPs; validity data was less robust.
PMID- 25850129
TI - Using concept maps in a modified team-based learning exercise.
AB - Medical school education has traditionally been driven by single discipline
teaching and assessment. Newer medical school curricula often implement an organ
based approach that fosters integration of basic science and clinical
disciplines. Concept maps are widely used in education. Through diagrammatic
depiction of a variety of concepts and their specific connections with other
ideas, concept maps provide a unique perspective into learning and performance
that can complement other assessment methods commonly used in medical schools. In
this innovation, we describe using concepts maps as a vehicle for a modified a
classic Team-Based Learning (TBL) exercise. Modifications to traditional TBL in
our innovation included replacing an individual assessment using multiple-choice
questions with concept maps as well as combining the group assessment and
application exercise whereby teams created concept maps. These modifications were
made to further assess understanding of content across the Fundamentals module
(the introductory module of the preclerkship curriculum). While preliminary,
student performance and feedback from faculty and students support the use of
concept maps in TBL. Our findings suggest concept maps can provide a unique means
of determining assessment of learning and generating feedback to students.
Concept maps can also demonstrate knowledge acquisition, organization of prior
and new knowledge, and synthesis of that knowledge across disciplines in a unique
way providing an additional means of assessment in addition to traditional
multiple-choice questions.
PMID- 25850130
TI - Referral for competency committee review for poor performance on the internal
medicine clerkship is associated with poor performance in internship.
AB - PURPOSE: To determine how students who are referred to a competency committee for
concern over performance, and ultimately judged not to require remediation,
perform during internship. METHODS: Uniformed Services University of the Health
Sciences' students who graduated between 2007 and 2011 were included in this
study. We compared the performance during internship of three groups: students
who were referred to the internal medicine competency committee for review who
met passing criterion, students who were reviewed by the internal medicine
competency committee who were determined not to have passed the clerkship and
were prescribed remediation, and students who were never reviewed by this
competency committee. Program Director survey results and United States Medical
Licensing Examination (USMLE) Step 3 examination results were used as the
outcomes of interest. RESULTS: The overall survey response rate for this 5-year
cohort was 81% (689/853). 102 students were referred to this competency committee
for review. 63/102 students were reviewed by this competency committee, given
passing grades in the internal medicine clerkship, and were not required to do
additional remediation. 39/102 students were given less than passing grades by
this competency committee and required to perform additional clinical work in the
department of medicine to remediate their performance. 751 students were never
presented to this competency committee. Compared to students who were never
presented for review, the group of reviewed students who did not require
remediation was 5.6 times more likely to receive low internship survey ratings in
the realm of professionalism, 8.6 times more likely to receive low ratings in the
domain of medical expertise, and had a higher rate of USMLE Step 3 failure (9.4%
vs. 2.8%). When comparing the reviewed group to students who were reviewed and
also required remediation, the only significant difference between groups
regarding professionalism ratings with 50% of the group requiring remediation
garnering low ratings compared to 18% of the reviewed group. CONCLUSIONS:
Students who are referred to a committee for review following completion of their
internal medicine clerkship are more likely to receive poor ratings in internship
and fail USMLE Step 3 compared to students whose performance in the medicine
clerkship does not trigger a committee review. These findings provide validity
evidence for our competency committee review in that the students identified as
requiring further clinical work had significantly higher rates of poor ratings in
professionalism than students who were reviewed by the competency committee but
not required to remediate. Additionally, students reviewed but not required to
remediate were nonetheless at risk of low internship ratings, suggesting that
these students might need some intervention prior to graduation.
PMID- 25850131
TI - Physical fitness and academic performance: a pilot investigation in USU medical
students.
AB - This study examined the correlations between physical fitness parameters and
standard measures of academic performance in a cohort of students at the
Uniformed Services University. Significant positive correlations were noted
between the average aerobic fitness score and preclerkship grade point average
(GPA; r = 0.37, p < 0.05) and cumulative GPA (r = 0.38, p < 0.05). Positive
correlations were also noted between the average overall fitness score and
preclerkship GPA (r = 0.34, p < 0.05), medical school cumulative GPA (r = 0.34, p
< 0.05), and the score on Step 1 of the national board examination (r = -0.33, p
< 0.05). Physical fitness may serve as one indicator to predict which students
will succeed in medical school and to identify those who are at risk for poor
performance and might benefit from a wellness intervention.
PMID- 25850132
TI - Novel examination for evaluating medical student clinical reasoning: reliability
and association with patients seen.
AB - BACKGROUND: Medical students learn clinical reasoning, in part, through patient
care. Although the numbers of patients seen is associated with knowledge
examination scores, studies have not demonstrated an association between patient
problems and an assessment of clinical reasoning. AIM: To examine the reliability
of a clinical reasoning examination and investigate whether there was association
between internal medicine core clerkship students' performance on this
examination and the number of patients they saw with matching problems during
their internal medicine clerkship. METHODS: Students on the core internal
medicine clerkship at the Uniformed Services University students log 11 core
patient problems based on the Clerkship Directors in Internal Medicine
curriculum. On a final clerkship examination (Multistep), students watch a
scripted video encounter between physician and patient actors that assesses three
sequential steps in clinical reasoning: Step One focuses on history and physical
examination; Step Two, students write a problem list after viewing additional
clinical findings; Step Three, students complete a prioritized differential
diagnosis and treatment plan. Each Multistep examination has three different
cases. For graduating classes 2010-2012 (n = 497), we matched the number of
patients seen with the problem most represented by the Multistep cases
(epigastric pain, generalized edema, monoarticular arthritis, angina, syncope,
pleuritic chest pain). We report two-way Pearson correlations between the number
of patients students reported with similar problems and the student's percent
score on: Step One, Step Two, Step Three, and Overall Test. RESULTS: Multistep
reliability: Step 1, 0.6 to 0.8; Step 2, 0.41 to 0.65; Step 3, 0.53 to 0.78;
Overall examination (3 cases): 0.74 to 0.83. For three problems, the number of
patients seen had small to modest correlations with the Multistep Examination of
Analytic Ability total score (r = 0.27 for pleuritic pain, p < 0.05, n = 81
patients; r = 0.14 for epigastric pain, p < 0.05, n = 324 patients; r = 0.19 for
generalized edema, p < 0.05, n = 118 patients). DISCUSSION or CONCLUSION:
Although a reliable assessment, student performance on a clinical reasoning
examination was weakly associated with the numbers of patients seen with similar
problems. This may be as a result of transfer of knowledge between clinical and
examination settings, the complexity of clinical reasoning, or the limits of
reliability with patient logs and the Multistep.
PMID- 25850133
TI - A curricular addition using art to enhance reflection on professional values.
AB - BACKGROUND: Art and humanities can enhance undergraduate medical education
curricular objectives. Most commonly, art is used to help students learn
observational skills, such as medical interviewing and physical diagnosis.
Educators concurrently struggle to find ways to meaningfully teach professional
values within crowded curricula. AIM: This curriculum aimed to combine art and
reflection to actively convey tenets of medical professionalism. SETTING:
Internal medicine clerkship at a single institution. PARTICIPANTS: Third-year
students. PROGRAM DESCRIPTION: Students reviewed an online module describing
attributes of medical professionalism before completing a 4-step written exercise
stimulated by viewing a work of art and based on a critical incident from their
own experiences. A faculty member reviewed the essays and facilitated small group
discussion to normalize the students' emotional responses and generalize their
observations to others. PROGRAM EVALUATION: The curriculum was acceptable to
students and enthusiastically received by faculty. Efforts to assess the effects
and durability of the exercise on student behavior are ongoing. DISCUSSION:
Artwork can enhance student reflection on professional values. This model
efficiently and creatively meets curricular professionalism objectives.
PMID- 25850134
TI - Dual process theory and intermediate effect: are faculty and residents'
performance on multiple-choice, licensing exam questions different?
AB - BACKGROUND: Clinical reasoning is essential for the practice of medicine. Dual
process theory conceptualizes reasoning as falling into two general categories:
nonanalytic reasoning (pattern recognition) and analytic reasoning (active
comparing and contrasting of alternatives). The debate continues regarding how
expert performance develops and how individuals make the best use of analytic and
nonanalytic processes. Several investigators have identified the unexpected
finding that intermediates tend to perform better on licensing examination items
than experts, which has been termed the "intermediate effect." PURPOSE: We
explored differences between faculty and residents on multiple-choice questions
(MCQs) using dual process measures (both reading and answering times) to inform
this ongoing debate. METHOD: Faculty (board-certified internists; experts) and
residents (internal medicine interns; intermediates) answered live licensing
examination MCQs (U.S. Medical Licensing Examination Step 2 Clinical Knowledge
and American Board of Internal Medicine Certifying Examination) while being
timed. We conducted repeated analysis of variance to compare the 2 groups on
average reading time, answering time, and accuracy on various types of items.
RESULTS: Faculty and residents did not differ significantly in reading time [F
(1,35) = 0.01, p = 0.93], answering time [F (1,35) = 0.60, p = 0.44], or accuracy
[F (1,35) = 0.24, p = 0.63] regardless of easy or hard items. DISCUSSION: Dual
process theory was not evidenced in this study. However, this lack of difference
between faculty and residents may have been affected by the small sample size of
participants and MCQs may not reflect how physicians made decisions in actual
practice setting.
PMID- 25850135
TI - Development and initial validation of a program director's evaluation form for
medical school graduates.
AB - BACKGROUND: In the early 1990 s, our group of interdepartmental academicians at
the Uniformed Services University (USU) developed a PGY-1 (postgraduate year 1)
program director evaluation form. Recently, we have revised it to better align
with the core competencies established by the Accreditation Council for Graduate
Medical Education. We also included items that reflected USU's military-unique
context. PURPOSE: To collect feasibility, reliability, and validity evidence for
our revised survey. METHOD: We collected PGY-1 data from program directors (PD)
who oversee the training of military medical trainees. The cohort of the present
study consisted of USU students graduating in 2010 and 2011. We performed
exploratory factor analysis (EFA) to examine the factorial validity of the survey
scores and subjected each of the factors identified in the EFA to an internal
consistency reliability analysis. We then performed correlation analysis to
examine the relationship between PD ratings and students' medical school grade
point averages (GPAs) and performance on U.S. Medical Licensing Examinations Step
assessments. RESULTS: Five factors emerged from the EFA--Medical Expertise,
Military-unique Practice, Professionalism, System-based Practice, and
Communication and Interpersonal Skills." The evaluation form also showed good
reliability and feasibility. All five factors were more strongly associated with
students' GPA in the initial clerkship year than the first 2 years. Further,
these factors showed stronger correlations with students' performance on Step 3
than other Step Examinations. CONCLUSIONS: The revised PD evaluation form seemed
to be a valid and reliable tool to gauge medical graduates' first-year internship
performance.
PMID- 25850136
TI - Development and initial validation of a program director's evaluation form for
third-year residents.
AB - BACKGROUND: Using a previously developed postgraduate year (PGY)-1 program
director's evaluation survey, we developed a parallel form to assess more senior
residents (PGY-3). The PGY-3 survey, which aligns with the core competencies
established by the Accreditation Council for Graduate Medical Education, also
includes items that reflect our institution's military-unique context. PURPOSE:
To collect feasibility, reliability, and validity evidence for the new PGY-3
evaluation. METHODS: We collected PGY-3 data from program directors who oversee
the education of military residents. The current study's cohort consisted of
Uniformed Services University of the Health Sciences students graduating in 2008,
2009, and 2010. We performed exploratory factor analysis (EFA) to examine the
internal structure of the survey and subjected each of the factors identified in
the EFA to an internal consistency reliability analysis. We then performed
correlation analysis to examine the relationships between PGY-3 ratings and
several OUTCOMES: PGY-1 ratings, cumulative medical school grade point average
(GPA), and performance on U.S. Medical Licensing Examinations (USMLE) Step 1,
Step 2 Clinical Knowledge, and Step 3. RESULTS: Of the 510 surveys we
distributed, 388 (76%) were returned. Results from the EFA suggested four
factors: "Medical Expertise," "Professionalism," "Military-unique Practice," and
"Systems-based Practice." Scores on these four factors showed good internal
consistency reliability, as measured by Cronbach's alpha (alpha ranged from 0.92
to 0.98). Further, as expected, "Medical Expertise" and "Professionalism" had
small to moderate correlations with cumulative medical school GPA and performance
on the USMLE Step examinations. CONCLUSIONS: The new program director's
evaluation survey instrument developed in this study appears to be feasible, and
the scores that emerged have reasonable evidence of reliability and validity in a
sample of third-year residents.
PMID- 25850137
TI - Career accomplishments of Uniformed Services University of the Health Sciences
medical graduates: classes 1980-2001.
AB - PURPOSE: To report accomplishments of graduates of the F. Edward Hebert School of
Medicine who have left, retired, or are near the end of their uniformed career in
several professional domains: military career milestones, medical professional
education, academic landmarks, and leadership. METHODS: This study utilized an
earlier questionnaire that was modified to capture additional career landmarks
and improve the clarity of several items. The modified survey was sent
electronically to alumni who graduated from 1980-2001 in March, 2012. RESULTS:
The questionnaire was sent to 2,825 alumni for whom we had e-mail addresses. We
estimate that we reached 2,400 alumni. A total of 1,189 alumni returned the
questionnaire, yielding an estimated response rate of 50%. For this cohort, the
board certification was 95%, over 20% obtained additional degrees, 92.8% had
worked as a full-time physician, nearly two-thirds had deployed for combat, 13.9%
had received the Legion of Merit, and 68.6% had published at least one peer
reviewed manuscript. CONCLUSION: Many accomplishments including board
certification rates, deployment experience, academic and military leadership
positions, military awards, promotion rates, and academic medicine contributions
are indicators that USU is continuing to meet its unique mission.
PMID- 25850138
TI - Assessing curriculum effectiveness: a survey of Uniformed Services University
medical school graduates.
AB - PURPOSE: This study assessed alumni perceptions of their preparedness for
clinical practice using the Accreditation Council for Graduate Medical Education
(ACGME) competencies. We hypothesized that our alumni's perception of
preparedness would be highest for military-unique practice and professionalism
and lowest for system-based practice and practice-based learning and improvement.
METHOD: 1,189 alumni who graduated from the Uniformed Services University (USU)
between 1980 and 2001 completed a survey modeled to assess the ACGME competencies
on a 5-point, Likert-type scale. Specifically, self-reports of competencies
related to patient care, communication and interpersonal skills, medical
knowledge, professionalism, systems-based practice, practice-based learning and
improvement, and military-unique practice were evaluated. RESULTS: Consistent
with our expectations as the nation's military medical school, our graduates were
most confident in their preparedness for military-unique practice, which included
items assessing military leadership (M = 4.30, SD = 0.65). USU graduates also
indicated being well prepared for the challenges of residency education in the
domain of professionalism (M = 4.02, SD = 0.72). Self-reports were also high for
competencies related to patient care (M = 3.86, SD = 0.68), communication and
interpersonal skills (M = 3.88, SD = 0.66), and medical knowledge (M = 3.78, SD =
0.73). Consistent with expectations, systems-based practice (M = 3.50, SD = 0.70)
and practice-based learning and improvement (M = 3.57, SD = 0.62) were the lowest
rated competencies, although self-reported preparedness was still quite high.
DISCUSSION: Our findings suggest that, from the perspective of our graduates, USU
is providing both an effective military-unique curriculum and is preparing
trainees for residency training. Further, these results support the notion that
graduates are prepared to lead and to practice medicine in austere environments.
Compared to other competencies that were assessed, self-ratings for systems-based
practice and practice-based learning and improvement were the lowest, which
suggests the need to continue to improve USU education in these areas.
PMID- 25850139
TI - Relationship of neuroimaging to typical sleep times during a clinical reasoning
task: a pilot study.
AB - BACKGROUND: Sleep deprivation and fatigue have been associated with medical
errors, clinical performance decrements, and reduced quality of life for both
practicing physicians and medical students. Greater understanding of the impact
of sleep quantity on clinical reasoning could improve patient care. The purpose
of our pilot study was to examine relationships between clinical reasoning
(assessed by functional magnetic resonance imaging) and sleep time (measured in
different ways by actigraphy) while answering multiple-choice questions (MCQs)
from licensing agencies. METHODS: Residents and faculty were administered a
clinical reasoning exercise (MCQs from licensing bodies) during functional
magnetic resonance imaging. Usual sleep patterns were sampled with actigraphy.
Covariate analysis was used to examine the relationship between sleep duration
(mean sleep, minimum sleep, maximum sleep) and brain activity during clinical
reasoning (solving MCQs from licensing bodies). RESULTS: The mean sleep time over
the duration of monitoring for the group was 7.19 hours (SD 0.66) with a range of
6.1 to 8.1 hours (internal medicine faculty 7.1 hours, SD 0.41; internal medicine
residents 7.27 hours, SD 0.92). There was a negative relationship between
activation in the prefrontal cortex and minimum sleep time while reflecting on
MCQs. CONCLUSION: Our findings provide evidence that the quantity of sleep can
modulate brain activity while completing a clinically meaningful task that should
be confirmed in larger studies. Our findings suggest that the construct of
sleepiness may be more complex than appreciated by many and that the most
important of these sleep measures in terms of outcomes remains to be determined.
PMID- 25850140
TI - The place of USU among America's allies: reflections from the Surgeon General of
the Canadian Armed Forces.
PMID- 25850141
TI - Reassessing student potential for medical school success: distance traveled,
grit, and hardiness.
PMID- 25850142
TI - A model for teaching reflective practice.
PMID- 25850143
TI - Leadership education and development at the Uniformed Services University.
PMID- 25850145
TI - Academic change management: leadership lessons from curricular reform.
PMID- 25850144
TI - Successful strategies for integrating bedside ultrasound into undergraduate
medical education.
AB - Nearly all physician specialties currently utilize bedside ultrasound, and its
applications continue to expand. Bedside ultrasound is becoming a core skill for
physicians; as such, it should be taught during undergraduate medical education.
When ultrasound is integrated in a longitudinal manner beginning in the
preclerkship phase of medical school, it not only enhances teaching the basic
science topics of anatomy, physiology, and pathology but also ties those skills
and knowledge to the clerkship phase and medical decision-making. Bedside
ultrasound is a natural bridge from basic science to clinical science. The
Uniformed Services University of the Health Sciences, F. Edward Hebert School of
Medicine is currently in its fourth year of implementing an integrated ultrasound
curriculum in the school of medicine. In our experience, successful integration
of a bedside ultrasound curriculum should: align with unique focuses of a medical
schools' mission, simplify complex anatomy through multimodal teaching, correlate
to teaching of the physical examination, solidify understanding of physiology and
pathology, directly link to other concurrent content, narrow differential
diagnoses, enhance medical decision-making, improve procedural skills, match to
year-group skillsets, develop teaching and leadership abilities, and have
elective experiences for advanced topics.
PMID- 25850146
TI - Yes, but does it produce better doctors?
PMID- 25850147
TI - Learning throughout a continuum, an innovative and feasible educational agenda!
PMID- 25850149
TI - The Uniformed Services University of the Health Sciences: a leadership academy
for military medical officers in the U.S. Navy.
PMID- 25850148
TI - The long-term career outcome study: lessons learned and implications for
educational practice.
AB - The work of the Long-Term Career Outcome Study has been a program of scholarship
spanning 10 years. Borrowing from established quality assurance literature, the
Long-Term Career Outcome Study team has organized its scholarship into three
phases; before medical school, during medical school, and after medical school.
The purpose of this commentary is to address two fundamental questions: (1) what
has been learned? and (2) how does this knowledge translate to educational
practice and policy now and into the future? We believe that answers to these
questions are relevant not only to our institution but also to other educational
institutions seeking to provide high-quality health professions education.
PMID- 25850150
TI - The Uniformed Services University of the Health Sciences: developing career
committed military medical officers.
PMID- 25850151
TI - Measuring individual differences in driver inattention: further validation of the
attention-related driving errors scale.
AB - OBJECTIVE: The aim of this research was (a) to study driver inattention as a
trait-like variable and (b) to provide new evidence of validity for the Attention
Related Driving Errors Scale (ARDES). BACKGROUND: Driving inattention is
approached from an individual differences perspective. We are interested in how
drivers vary in their propensity to experience failures of attention and in the
methods to measure these differences. METHOD: In a first sample (n = 301), we
tested, via confirmatory factor analysis, a new theoretical model for the ARDES.
In a second sample (n = 201), we evaluated the relationship between inattention
and internal and external sources of distraction and social desirability bias in
ARDES responses. A subsample (n = 65) was reevaluated to study temporal stability
of the ARDES scores. RESULTS: Errors measured by the ARDES can be classified
according to the driving task level at which they occur (navigation, maneuvering,
or control). Differences in ARDES scores based on collision history were
observed. ARDES was related to internal sources of distraction and was
independent of the level of exposure to distracting activities. Test-retest
showed a high degree of stability in ARDES scores. Low correlations were found
with a social desirability measure. CONCLUSION: ARDES appears to measure a
personal trait that remains relatively stable over time and is relatively
independent of distracting activities. New evidence of validity emerged for this
self-report. APPLICATION: ARDES can be used to measure individual differences in
driving inattention and to help tailor preventive interventions for inattentive
drivers. It can serve as an instrument of driver self-assessment in educational
and training contexts.
PMID- 25850152
TI - A comparison of abdominal muscle thickness changes after a lifting task in
subjects with and without chronic low-back pain.
AB - OBJECTIVE: Using ultrasound imaging, the abdominal muscles' response to the back
extensor muscle fatigue was assessed in subjects with chronic low-back pain
(CLBP). BACKGROUND: Lumbar muscle fatigue is a common occurrence among workers.
Alteration in motor coordination is one consequence of muscular fatigue.
According to previous studies, CLBP subjects use their back and abdominal muscles
in different ways, but questions remain about abdominal muscle responses to back
muscle fatigue in CLBP patients. METHOD: Thirteen CLBP patients and 15 healthy
subjects participated in this study. The thickness of abdominal muscles-including
transverse abdominis (TrA), internal oblique abdominis (IO), and external oblique
abdominis (EO) muscles-was measured in standing position with and without axial
loads before and after a lifting fatigue task. RESULTS: The results reveal a
significant difference for the main effects of group on percentage of change in
TrA thickness (F = 8.9, p = .004). Percentage of change in thickness of TrA was
10% greater in the CLBP group. Although IO thickness displayed greater percentage
of change in the CLBP group, the difference between groups was not significant.
CONCLUSION: Abdominal muscle behavior changes with back-muscle fatigue in both
healthy and CLBP subjects, but responses were more exaggerated in CLBP patients.
APPLICATION: Ultrasound imaging technique can provide critical information about
the effect of fatigue on spinal muscle activation and consequently about the
stability of the spine. As a more applicable and easy technique, ergonomists can
use ultrasound imaging in musculoskeletal system assessment in worker populations
in future studies.
PMID- 25850153
TI - Effects of carrying a backpack in an asymmetrical manner on the asymmetries of
the trunk and parameters defining lateral flexion of the spine.
AB - OBJECTIVE: The aim of this study was to examine changes in the body posture
parameters defining asymmetry of the trunk and lateral flexion of the spine in
children while carrying a backpack weighing 10% of a child's weight. BACKGROUND:
Carrying a backpack may negatively affect the posture of schoolchildren and
contribute to spinal pain. METHOD: The study involved 162 primary school students
ages 11 to 13 years. The parameters describing body posture were assessed with a
backpack carried on the right or left shoulder as well as without a load. To
assess the predefined parameters, we used the CQ Elektronik System, employing the
photogrammetric method. RESULTS: Trunk inclination shifted significantly in the
opposite direction to the shoulder the backpack was carried on, and an increase
in shoulder asymmetry was also found. We also observed a more pronounced right
side lateral flexion of the spine when the backpack was carried on the right
shoulder and an analogous relationship for the left side. CONCLUSION: The results
of this study show that carrying a backpack in an asymmetrical manner negatively
affects spine, even if the backpack weight constitutes 10% of the child's weight,
which has been previously recommended as a safe load for a child's shoulders.
APPLICATION: We suggest that the issue of safe backpack weight be reassessed and
that students be taught basic ergonomic principles on how to carry loads. Changes
to the management pattern of carrying textbooks to and from school also should be
considered.
PMID- 25850154
TI - Multiaxis grip characteristics for varying handle diameters and effort.
AB - OBJECTIVE: A multiaxis dynamometer was used to quantify grip force vector angles
and longitudinal centers of pressure (COPs) while varying handle size and effort
used. BACKGROUND: Authors of many studies have examined maximum grip strength
using scalar instruments; a few have measured two-axis forces limited to one or
more finger contact. This novel dynamometer uses two instrumented beams that are
grasped by the distal fingers and proximal palm to compute two orthogonal
components of force and the longitudinal COP through which the force acts.
METHOD: Sixteen healthy, right-handed participants grasped the multiaxis
dynamometer with plastic handles ranging in diameter from 3.81 to 7.62 cm. They
were required to scale their effort to 25%, 50%, 75%, and 100% of maximum.
RESULTS: Grip force vector angles were affected by both handle diameter and
effort level, with angles increasing an average of 8.1 degrees from the least to
greatest effort. Longitudinal COP, averaged among the two beams, shifted 1.75 cm
radially as handle diameter increased from 3.81 cm to 7.62 cm. Average COP along
the beam in contact with the distal finger segments shifted 0.75 cm ulnarly as
effort level increased from 25% to 100% of maximum. CONCLUSION: Grip force
characteristics changed with handle diameter and effort level. Overall grip force
magnitude comprised both force components measured. APPLICATION: Understanding
grip characteristics should be important for handle and grip design and for
evaluating hand function.
PMID- 25850155
TI - Arm and neck pain in ultrasonographers.
AB - OBJECTIVE: The aim of this study was to evaluate the prevalence of upper-body
quadrant pain among ultrasonographers and to evaluate the association between
individual ergonomics, musculoskeletal disorders, and occurrence of neck pain.
METHOD: A hundred and ten (N = 110) Belgian and Dutch male and female hospital
ultrasonographers were consecutively enrolled in the study. Data on work-related
ergonomic and musculoskeletal disorders were collected with an electronic
inquiry, including questions regarding ergonomics (position of the screen, high
low table, and ergonomic chair), symptoms (neck pain, upper-limb pain), and work
related factors (consecutive working hours a day, average working hours a week).
RESULTS: Subjects with the screen on their left had significantly more neck pain
(odds ratio [OR] = 3.6, p = .0286). Depending on the workspace, high-low tables
increased the chance of developing neck pain (OR = 12.9, p = .0246). A screen at
eye level caused less neck pain (OR = .22, p = .0610). Employees with a fixed
working space were less susceptible to arm pain (OR = 0.13, p = .0058). The
prevalence of arm pain was significantly higher for the vascular department
compared to radiology, urology, and gynecology departments (OR = 9.2, p = .0278).
CONCLUSIONS: Regarding prevention of upper-limb pain in ultrasonograph, more
attention should be paid to the work environment and more specialty to the
ultrasound workstation layout. Primary ergonomic prevention could provide a
painless work situation for the ultrasonographer. APPLICATION: Further research
on the ergonomic conditions of ultrasonography is necessary to develop ergonomic
solutions in the work environment that will help to alleviate neck and arm pain.
PMID- 25850156
TI - Sideways camera rotations of 90 degrees and 135 degrees result in poorer
performance of laparoscopic tasks for novices.
AB - OBJECTIVE: The aim of this study was to determine the impact of sideways
visuomotor rotations between 0 degrees and 180 degrees on novice performance in
a laparoscopic simulator. BACKGROUND: The laparoscopic surgical environment often
involves visuomotor rotations because the laparoscope may be placed to the
surgeon's side. Basic research by Cunningham indicated that visuomotor rotations
between 90 degrees and 135 degrees result in peak performance decrements.
Research by Ames and colleagues failed to replicate Cunningham's results in the
laparoscopic environment, possibly due to (a) confounds from carryover effects or
(b) use of an alternative laparoscopic training task rather than the straight
line pointing task used by Cunningham. Two experiments were conducted to
determine if Cunningham's results generalize to the laparoscopic environment when
controlling for carryover effects for a three-dimensional "straight-line"
pointing task (Experiment 1) and a laparoscopic training task (Experiment 2).
METHOD: In Experiments 1 and 2, participants were assigned to one of five
visuomotor rotations: 0 degrees , 45 degrees , 90 degrees , 135 degrees , or 180
degrees . Utilizing a laparoscopic simulator, participants performed either a
three-dimensional pointing task (Experiment 1) or a peg transfer task (Experiment
2). RESULTS: In both experiments, visuomotor rotations of 90 degrees or 135
degrees resulted in the poorest performance. CONCLUSION: When controlling for
carryover effects, Cunningham's results generalize to novices' performance of a
pointing and a peg transfer task in the laparoscopic environment. APPLICATIONS:
The results indicate that 90 degrees and 135 degrees sideways laparoscope
placements may result in worse performance for novices in the laparoscopic
environment, indicating potentially longer learning curves for these conditions
in the laparoscopic as well as other teleoperation environments.
PMID- 25850157
TI - Musculoskeletal disorder symptoms in correction officers: why do they increase
rapidly with job tenure?
AB - OBJECTIVE: In this study, we sought to explain the rapid musculoskeletal
symptomatology increase in correction officers (COs). BACKGROUND: COs are exposed
to levels of biomechanical and psychosocial stressors that have strong
associations with musculoskeletal disorders (MSDs) in other occupations, possibly
contributing to their rapid health deterioration. METHOD: Baseline survey data
from a longitudinal study of COs and manufacturing line workers were used to
model musculoskeletal symptom prevalence and intensity in the upper (UE) and
lower (LE) extremity. Outcomes were regressed on demographics and biomechanical
and psychosocial exposures. RESULTS: COs reported significantly higher prevalence
and intensity of LE symptoms compared to the industrial workers. In regression
models, job tenure was a primary driver of CO musculoskeletal outcomes. In CO
models, a single biomechanical exposure, head and arms in awkward positions,
explained variance in both UE and LE prevalence (beta of 0.338 and 0.357,
respectively), and low decision latitude was associated with increased LE
prevalence and intensity (beta of 0.229 and 0.233, respectively). Manufacturing
models were less explanatory. Examining demographic associations with exposure
intensity, we found none to be significant in manufacturing, but in CO models,
important psychosocial exposure levels increased with job tenure. CONCLUSION:
Symptom prevalence and intensity increased more rapidly with job tenure in
corrections, compared to manufacturing, and were related to both biomechanical
and psychosocial exposures. Tenure-related increases in psychosocial exposure
levels may help explain the CO symptom increase. APPLICATION: Although exposure
assessment improvements are proposed, findings suggest focusing on improving the
psychosocial work environment to reduce MSD prevalence and intensity in
corrections.
PMID- 25850158
TI - Visual information processing from multiple displays.
AB - OBJECTIVE: In this study, we examined how effectively people can monitor new
stimuli on a peripheral display while carrying out judgments on an adjacent
central display. BACKGROUND: Improved situation awareness is critical for
improved operator performance in aviation and many other domains. Given the
limited extent of foveal processing, acquiring additional information from
peripheral vision offers high potential gains. METHOD: Participants carried out a
sequence of central perceptual judgments while simultaneously monitoring the
periphery for new stimuli. Peripheral detection was measured as a function of
central-judgment difficulty, the relative timing of the two tasks, and peripheral
event rate. RESULTS: Participants accurately detected and located peripheral
targets, even at the highest eccentricity explored here (~30 degrees ).
Peripheral detection was not reduced by increased central-task difficulty but was
reduced when peripheral targets arrived later in the processing of central
stimuli and when peripheral events were relatively rare. CONCLUSION: Under
favorable conditions-high-contrast stimuli and high event rate-people can
successfully monitor peripheral displays for new events while carrying out an
unrelated continuous task on an adjacent display. APPLICATION: In many fields,
such as aviation, existing displays were designed with low-contrast stimuli that
provide little opportunity for peripheral vision. With appropriate redesign,
operators might successfully monitor multiple displays over a large visual field.
Designers need to be aware of nonvisual factors, such as low event rate and
relative event timing, that can lead to failures to detect peripheral stimuli.
PMID- 25850159
TI - Situation awareness measures for simulated submarine track management.
AB - OBJECTIVE: The aim of this study was to examine whether the Situation Present
Assessment Method (SPAM) and the Situation Awareness Global Assessment Technique
(SAGAT) predict incremental variance in performance on a simulated submarine
track management task and to measure the potential disruptive effect of these
situation awareness (SA) measures. BACKGROUND: Submarine track managers use
various displays to localize and track contacts detected by own-ship sensors. The
measurement of SA is crucial for designing effective submarine display interfaces
and training programs. METHOD: Participants monitored a tactical display and
sonar bearing-history display to track the cumulative behaviors of contacts in
relationship to own-ship position and landmarks. SPAM (or SAGAT) and the Air
Traffic Workload Input Technique (ATWIT) were administered during each scenario,
and the NASA Task Load Index (NASA-TLX) and Situation Awareness Rating Technique
were administered postscenario. RESULTS: SPAM and SAGAT predicted variance in
performance after controlling for subjective measures of SA and workload, and SA
for past information was a stronger predictor than SA for current/future
information. The NASA-TLX predicted performance on some tasks. Only SAGAT
predicted variance in performance on all three tasks but marginally increased
subjective workload. CONCLUSION: SPAM, SAGAT, and the NASA-TLX can predict unique
variance in submarine track management performance. SAGAT marginally increased
subjective workload, but this increase did not lead to any performance decrement.
APPLICATION: Defense researchers have identified SPAM as an alternative to SAGAT
because it would not require field exercises involving submarines to be paused.
SPAM was not disruptive, but it is potentially problematic that SPAM did not
predict variance in all three performance tasks.
PMID- 25850160
TI - Driving speed of young novice and experienced drivers in simulated hazard
anticipation scenes.
AB - OBJECTIVE: In this study, we aimed to demonstrate analysis methods that are
sensitive to speed-related differences between experienced and young novice
drivers. These differences may be linked to determining which group is better at
anticipating hazards. BACKGROUND: Awareness of hazardous situations, especially
potential ones, is a major discriminator between experienced and young novice
drivers who tend to misidentify potential hazards in the traffic environment.
METHOD: Experienced and young novice drivers were asked to drive a sequence of 14
scenarios in a driving simulator. Scenarios were created in two city areas,
residential and business district, and included various types of hazards. Group
homogeneity of speed for each group of drivers was computed for each scenario,
and two business district scenarios were subjected to piecewise linear regression
analysis. RESULTS: Group homogeneity analysis showed consistent and significant
experience-based differences across all scenarios, revealing that the experienced
drivers as a group were more homogenous in choosing their driving speed.
Differences between groups were larger in the business district where speed was
less restricted. Piecewise linear regression analysis revealed that experienced
drivers approached uncontrolled intersections by slowing down and responded
earlier to materialized events. CONCLUSION: Young novice drivers were more likely
than experienced drivers to choose diverse values of speed at any given road
section, presumably due to their poor awareness of potential and hidden hazards.
Unlike other analysis methods, it is argued that group homogeneity of speed is a
more sensitive measurement to reveal these gaps. APPLICATION: Speed management
could be the basis of future hazard anticipation simulator assessments.
PMID- 25850161
TI - Dynamic vibrotactile signals for forward collision avoidance warning systems.
AB - OBJECTIVE: Four experiments were conducted in order to assess the effectiveness
of dynamic vibrotactile collision-warning signals in potentially enhancing safe
driving. BACKGROUND: Auditory neuroscience research has demonstrated that
auditory signals that move toward a person are more salient than those that move
away. If this looming effect were found to extend to the tactile modality, then
it could be utilized in the context of in-car warning signal design. METHOD: The
effectiveness of various vibrotactile warning signals was assessed using a
simulated car-following task. The vibrotactile warning signals consisted of
dynamic toward-/away-from-torso cues (Experiment 1), dynamic versus static
vibrotactile cues (Experiment 2), looming-intensity- and constant-intensity
toward-torso cues (Experiment 3), and static cues presented on the hands or on
the waist, having either a low or high vibration intensity (Experiment 4).
RESULTS: Braking reaction times (BRTs) were significantly faster for toward-torso
as compared to away-from-torso cues (Experiments 1 and 2) and static cues
(Experiment 2). This difference could not have been attributed to differential
responses to signals delivered to different body parts (i.e., the waist vs.
hands; Experiment 4). Embedding a looming-intensity signal into the toward-torso
signal did not result in any additional BRT benefits (Experiment 3). CONCLUSION:
Dynamic vibrotactile cues that feel as though they are approaching the torso can
be used to communicate information concerning external events, resulting in a
significantly faster reaction time to potential collisions. APPLICATION: Dynamic
vibrotactile warning signals that move toward the body offer great potential for
the design of future in-car collision-warning system.
PMID- 25850162
TI - Reading text while driving: understanding drivers' strategic and tactical
adaptation to distraction.
AB - OBJECTIVE: In this study, we investigated how drivers adapt secondary-task
initiation and time-sharing behavior when faced with fluctuating driving demands.
BACKGROUND: Reading text while driving is particularly detrimental; however, in
real-world driving, drivers actively decide when to perform the task. METHOD: In
a test track experiment, participants were free to decide when to read messages
while driving along a straight road consisting of an area with increased driving
demands (demand zone) followed by an area with low demands. A message was made
available shortly before the vehicle entered the demand zone. We manipulated the
type of driving demands (baseline, narrow lane, pace clock, combined), message
format (no message, paragraph, parsed), and the distance from the demand zone
when the message was available (near, far). RESULTS: In all conditions, drivers
started reading messages (drivers' first glance to the display) before entering
or before leaving the demand zone but tended to wait longer when faced with
increased driving demands. While reading messages, drivers looked more or less
off road, depending on types of driving demands. CONCLUSIONS: For task
initiation, drivers avoid transitions from low to high demands; however, they are
not discouraged when driving demands are already elevated. Drivers adjust time
sharing behavior according to driving demands while performing secondary tasks.
Nonetheless, such adjustment may be less effective when total demands are high.
APPLICATION: This study helps us to understand a driver's role as an active
controller in the context of distracted driving and provides insights for
developing distraction interventions.
PMID- 25850163
TI - Suggested methods to improve physician-hospital relationships in Canada.
AB - This article focuses on the suggested methods to improve the quality of Physician
Hospital Relations (PHRs) in the Canadian healthcare system based on the opinions
and perspectives of healthcare leaders across all provinces and territories who
participated in the Canadian National Study of Interprofessional Relationships
between Physicians and Hospital Administrators (CANSIRPH). Improving PHRs equals
higher patient care quality, error reduction, well-managed budgets, and
professional satisfaction of clinical and non-clinical leaders.
PMID- 25850164
TI - The owners have a right to be heard: Patient voice in design and performance
improvement.
AB - The Canadian taxpayer is an owner of the healthcare system and the owners have a
right to be heard. This article encourages leaders both formal and informal to
create cultures that promote ASKing questions to test assumptions held, LISTENing
to hear the patient voice, and TALKing with patients and families to create new
conversations and narratives. Looking at the label, "healthcare system" what's
your contribution to creating health, how will you dedicate yourself to caring
about the healthcare consumer and care provider, and what will be your role in
creating a new and improved system? An implied question at the foundation of the
article is this: Is the difference between managing and leading a difference of
empathy?
PMID- 25850165
TI - Health leaders and ethical dimensions of managing "value adds".
AB - Value adds refers to an "extra" feature or features of an item of interest
(product, service, and person) that go beyond the standard expectations and
provide something more, even if the cost is higher to the client or purchaser.
This article looks at the ethical dimensions health leaders face in managing
value adds and provides recommendations for ensuring that ethical practice is
being followed consistently. A summary of several healthcare-related codes of
ethics are provided to support the recommendations.
PMID- 25850166
TI - In vivo phytochrome-mediated perception of reflected light signals.
AB - The spectrophotometric assay of phytochrome in vivo in etiolated plant material
was used to determine the effects of changes in reflected light on the state of
the photoreceptor in etiolated seedlings exposed simultaneously to direct and
reflected light. Changes in reflected light that were small in terms of the total
(direct + reflected) radiation incident on the seedlings produced detectable
changes in the state of phytochrome in vivo. The contribution of reflected light
to the state of phytochrome in vertical organs was greater than expected from its
low contribution to total incident light. These data from laboratory studies
complement and are consistent with results of field studies on the effects of
light reflected from neighboring vegetation on plant growth under natural
radiation conditions.
PMID- 25850167
TI - The luck of the new graduate nurse.
PMID- 25850168
TI - Nurse wants action on pay and superannuation.
PMID- 25850169
TI - Five-pointed star article praised.
PMID- 25850170
TI - How is your medal holding on?
PMID- 25850172
TI - The Kaiwhakahaere comments.
PMID- 25850171
TI - Valuing all human life.
PMID- 25850173
TI - Slow progress in MECA negotiations.
PMID- 25850174
TI - Care rationing 'untenable'.
PMID- 25850175
TI - Supreme Court declines appeal on equal pay case.
PMID- 25850176
TI - Student enrolments steady.
PMID- 25850177
TI - Evaluation recommends CCDM in all DHBs.
PMID- 25850178
TI - Rates of older women in the workforce increasing.
PMID- 25850180
TI - Masked tutor brings patient to 'life'.
PMID- 25850179
TI - What nurses think about professionalism.
PMID- 25850181
TI - How well do new graduates manage medications?
PMID- 25850182
TI - Peer supervision requires ongoing commitment.
PMID- 25850184
TI - Knowing your legislation.
PMID- 25850183
TI - Osteoporosis--fragile bones.
PMID- 25850185
TI - Comparing nursing competencies.
PMID- 25850186
TI - Why we should value younger nurses.
PMID- 25850187
TI - Hinerangi's legacy lives on.
PMID- 25850189
TI - Mentoring, technology, team work, history.
PMID- 25850188
TI - Building the Maori nursing workforce.
PMID- 25850190
TI - Primary health care: MECA overwhelmingly endorsed.
PMID- 25850191
TI - DHBs: new birthing service in Buller but closure in Stratford.
PMID- 25850192
TI - Private hospitals: hospice MECA underway.
PMID- 25850193
TI - Aged care: extra government money not going to Radius staff.
PMID- 25850194
TI - Perioperative nursing: OR education.
PMID- 25850195
TI - Dermatological and cosmeceutical benefits of Glycine max (soybean) and its active
components.
AB - Glycine max, known as the soybean or soya bean, is a species of legume native to
East Asia. Soya beans contain many functional components including phenolic
acids, flavonoids, isoflavonoids (quercetin, genistein, and daidzein), small
proteins (Bowman-Birk inhibitor, soybean trypsin inhibitor) tannins, and
proanthocyanidins. Soybean seeds extract and fresh soymilk fractions have been
reported to possess the cosmeceutical and dermatological benefits such as anti
inflammatory, collagen stimulating effect, potent anti-oxidant scavenging peroxyl
radicals, skin lightening effect and protection against UV radiation. Thus,
present review attempts to give a short overview on dermatological and
cosmeceutical studies of soybean and its bioactive compounds.
PMID- 25850196
TI - The role of prostanoids in the urinary bladder function and a potential use of
prostanoid-targeting pharmacological agents in bladder overactivity treatment.
AB - Overactive bladder (OAB) is a syndrome involving urinary urgency with
accompanying increased daytime urinary frequency and nocturia, with or without
urgency urinary incontinence, in the absence of an urinary tract infection or
other obvious pathology. The detailed OAB pathophysiology remains unclear. There
is evidence that OAB pathogenesis also includes abnormal bladder paracrine
activity, associated with release of local prostanoids. Those agents contribute
to disturbances of peripheral neuronal bladder control resulting in detrusor
instability. Thus, pharmacological agents abolishing prostanoid-induced bladder
overactivity seem to be a potential, future OAB therapeutical option. This paper
shortly describes the rationale for nonsteroidal antiinflammatory drugs (NSAIDs)
and EP-1 receptor antagonists administration in future OAB pharmacotherapy.
PMID- 25850197
TI - Solid state characterization of alpha-tocopherol in inclusion complexes with
cyclodextrins.
AB - The alternative for a pure soluble, sensible for physical and chemical conditions
oil form of alpha-tocopherol (alpha-T) is its complexation with cyclodextrins. A
different influence of cyclodextrins on the included substance demands a
stability investigation of the substance enclosed in a host-guest complex. Hence,
the thermal stability of alpha-T in inclusion complexes (InCs) with cyclodextrins
(CDs) was studied. The inclusion complexes were obtained by two different
methods: a lyophilization and a kneading method, and their formation was examined
by IR spectroscopy, differential scanning calorimetry and 1H-NMR spectroscopy.
The inclusion complexes were subjected to the test of accelerated aging at 323 K,
333 K, 338 and 343 K, for comparison alpha-T as a substance and physical mixtures
(PhM) of alpha-T with CDs were used. Changes in alpha-T concentration during the
experiment were followed by HPLC method and next, the products of thermal
decomposition were studied by LC-ESI-MS/MS method. The reaction of alpha-T
decomposition in inclusion complexes with CDs was found to be of the first order.
The same order of a decomposition reaction was observed in a sample of alpha-T as
a substance. It seems that cyclodextrins protect alpha-T against thermal
decomposition, moreover, the protective effect of natural beta-cyclodextrin (beta
CD) appears to be greater than that of 2-hydroxypropyl-beta-cyclodextrin (2-HP
beta-CD). However, the CDs do not influence the type of a formed product of
decomposition. This product, i.e., the dimer of alpha-T (m/z 859 Da), was found
in all tested samples. The protective effect of CDs and transformation from the
liquid state to the solid state of alpha-T can be used to create a new
pharmaceutical form--tablets with alpha-T.
PMID- 25850198
TI - Determination of neomycin in the form of neomycin derivative with dabsyl chloride
by thin layer chromatography and densitometry.
AB - A thin layer chromatographic-densitometric method has been developed for
identification and quantitative determination of neomycin derivative with dabsyl
chloride. The analysis of antibiotic was achieved on the silica gel TLC plates
with fluorescent indicator with n-butanol--2-butanone--25% ammonia--water (10 : 6
: 2 : 2, v/v/v/v) as the mobile phase. The densitometric measurements were made
at 460 nm. Under these conditions good separation of chosen aminoglycoside
antibiotic from reagent used to make a complex was obtained. The method is
characterized by high sensitivity, LOD from 0.1953 MUg per band and LOQ from
0.5918 MUg per band, wide linearity range from 0.5918 to 2.1960 MUg per band for
neomycin. The precision of the method was good; RSD varied from 1.17 to 2.05%.
Satisfactory results of validation of the method were also confirmed by
determination of selected antibiotic in pharmaceutical commercial preparation.
The results obtained by TLC-densitometric method were compared with those
obtained by spectrophotometric method.
PMID- 25850199
TI - Effect of chromatographic conditions on retention behavior and system efficiency
for HPTLC of selected psychotropic drugs on chemically bonded stationary phases.
AB - Selected psychotropic drug standards have been chromatographed on RP18, CN and
diol layers with a variety of aqueous and nonaqueous mobile phases. The effect of
buffers at acidic or basic pH, acetic acid, ammonia and diethylamine (DEA) in
aqueous mobile phases on retention, efficiency and peak symmetry was examined.
Improved peak symmetry and separation selectivity for investigated compounds were
observed when ammonia or DEA were used as mobile phase additives. The effect of
diethylamine concentration in aqueous eluents on retention, peak symmetry and
theoretical plate number obtained on CN plates was also investigated. Because of
the strong retention of these basic drugs on stationary phases bonded on silica
matrix, nonaqueous eluents containing medium polar diluents, strongly polar
modifiers and silanol blockers (ammonia or diethylamine) were applied. Aqueous
and nonaqueous eluent systems with the best selectivity and efficiency were used
for separate psychotropic drug standards' mixture on CN layer by 2D TLC.
PMID- 25850200
TI - The effect of lipoic acid administration on the urinary excretion of thiocyanate
in rats exposed to potassium cyanide.
AB - The oxidation of cyanide (CN-) to a much less toxic thiocyanate (SCN-) is the
main in vivo biochemical pathway for CN- detoxification. SCN- is excreted mainly
in urine. This study was performed to investigate the effect of lipoic acid (LA)
on the urinary excretion of thiocyanate (SCN-; rhodanate) in rats. Groups of the
animals were treated intraperitoneally (i.p.) as follows: group 1: potassium
cyanide (KCN) (1 mg/kg); group 2: KCN (1 mg/kg) + LA (100 mg/kg). Urine was
collected for 24 h and the pooled samples were examined for SCN- levels. The
obtained results indicated that the treatment of animals with potassium cyanide
and LA in combination significantly increased the urinary excretion of SCN- in
comparison with the respective values in the KCN-alone-treated group. It
indicates that LA increased the rate of CN- detoxification in rats.
PMID- 25850201
TI - Synthesis and antibacterial properties of pyrimidine derivatives.
AB - In this study, a series of syntheses was conducted on the pyrimidine system,
obtaining bisulfite carboxyl derivatives 4 and hydroxy derivatives 5. In
addition, a series of syntheses were carried out as a result of which both alkyl
and aromatic amines were obtained. Then, the attempt was made to cyclize these
amines in the Mannich reaction to pyrimido[4,5-d]pyrimidines 11, 12. After
determination of chemical structure using physicochemical tests, also by means of
crystallographic tests, all the newly obtained derivatives underwent
microbiological tests on bacterial strains and fungi. The most interesting
results of the microbiological tests are included later in the study.
PMID- 25850202
TI - Novel pyrrolopyrimidines and triazolopyrrolopyrimidines carrying a biologically
active sulfonamide moieties as anticancer agents.
AB - A new series of pyrroles 5, 6, pyrrolopyrimidines 8, 11-14, 16-29, triazolo
pyrrolopyrimidines 9, 10 and 15 carrying a biologically active sulfonamide
moities were synthesized using 2-amino-3-cyano-4-(4-bromophenyl)pyrrole 5 as a
strategic starting material. The structures of the prepared compounds were
confirmed by elemental analyses, IR, 1H-NMR and 13C-NMR data. All of the
synthesized compounds showed promising anticancer activity against breast cancer
cell line (MCF7) compared to doxorubicin as reference drug, especially compounds
5-17, 21-24 and 28 with better IC50 than that of doxorubicin. In order to suggest
the mechanism of action of their cytotoxic activities, molecular docking on the
active site of c-Src was done and good results were obtained.
PMID- 25850203
TI - Cytotoxic activity of some novel sulfonamide derivatives.
AB - The versatile synthons 2-chloro-N-(4-sulfamoylphenyl)acetamides la,b were used as
a key intermediates for the synthesis of sulfonamide derivatives with adamantyl
2, indene 3, morpholinophenyl 4, pipronyl 5, benzothiazole 6-8, pyrazole 9,
thiadiazole 10,11, quinoline 12, isoquinoline 13, thiazoles 14-19, acrylamides 20
24 and benzochromene 25 moieties via reaction with several nitrogen nucleophiles.
The newly synthesized compounds were screened in vitro for their anticancer
activity against breast cancer (MDA-MB-231) and colon cancer (HT-29) cell lines.
Compound 17 was found to be the most potent against breast cancer cell lines with
IC55 value 66.6 MUM compared with the reference drug 5-fluorouracil with IC50
value 77.28 MUM.
PMID- 25850204
TI - Synthesis and evaluation of anticonvulsant activity of N-(2,5-dimethylphenoxy)-
and N-[(2,3,5-trimethylphenoxy)alkyl]aminoalkanols.
AB - A series of new N-(2,5-dimethylphenoxy)- and N-(2,3,5
trimethylphenoxy)alkylaminoalkanols [I-XVII] was synthesized and evaluated for
anticonvulsant activity. Pharmacological tests included maximal electroshock
(MES) and subcutaneous pentetrazole seizure threshold (scMet) assays as well as
neurotoxicity (TOX) evaluation in mice after intraperitoneal (i.p.)
administration and/or in rats after oral (p.o.) administration. The most active
compound was R-2N-[(2,3,5-trimethylphenoxy)ethyl]aminobutan-1-ol, which exhibited
100% activity in MES at the dose of 30 mg/kg body weight (mice, i.p.) and 75%
activity in MES at 30 mg/kg b.w. (rats, p.o.) without neurotoxicity at the active
doses.
PMID- 25850205
TI - Synthesis and antiproliferative activity in vitro of new 2-thioxoimidazo[4,5
B]pyridine derivatives.
AB - Two series of 2-thioxoimidazo[4,5-b]pyridine derivatives have been synthesized
from 2,3-diaminopyridine (1) and 5-halogenosubstituted-2,3-diaminopyridines 2, 3.
Mannich bases 7 - 12 and 24 - 29, derivatives of 1-arylamino-6-halogeno-2
thioxoimidazo[4,5-b]pyridine were obtained with selected secondary amines:
morpholine, piperidine, 2-methoxyphenylpiperazine, pyrimidyn-2-yl-piperazine and
formaldehyde in ethanol. The structures 7 - 12 and 24 - 29 were confirmed by the
results of elementary analysis and their IR, 1H-NMR and MS spectra. All given
structures 7 - 12 have been optimized to get the most stable low energy
conformers. Synthesized compounds were of interest for biological studies or can
be substrates for further synthesis. The selected compounds 7 - 10, 12- 17, 22,
25, 27 - 29 were screened for their antiproliferative activity in vitro against
human cancer and normal mouse fibroblast cell lines.
PMID- 25850206
TI - Evaluation of anti-inflammatory, analgesic and antipyretic activities of Thymus
serphyllum Linn. in mice.
AB - The present study was conducted to evaluate the analgesic, anti-inflammatory and
antipyretic activities of Thymus serphyllum Linn. in mice. Anti-inflammatory
activity was evaluated by carrageenan and egg albumin induced paw edema in mice,
while analgesic activity was assessed using formalin induced paw licking and
acetic acid induced abdominal writhing in mice. For determination of antipyretic
activity, pyrexia was induced by subcutaneous injection of 20% yeast. All the
extracts produced significant anti-inflammatory effect however, ether extract
produced maximum effect 34% inhibition (p < 0.001) against carrageenan and 22% (p
< 0.01) inhibition against egg albumin induced paw edema in mice at the end of 3
h. Ether extract produced prominent analgesic effect 77% (p < 0.001) inhibition
in acetic acid induced abdominal writhing and 59% inhibition in formalin induced
paw licking model in mice, respectively. Ether extract also demonstrated
significant (p < 0.001) antipyretic activity against yeast induced pyrexia. The
plant showed no sign of toxicity up to the dose of 2000 mg/kg in mice. This study
supports the use of Thymus serphyllum in traditional medicine for inflammation
accompanied by pain and fever.
PMID- 25850207
TI - In vitro antioxidant activity and GC-MS analysis of the ethanol and aqueous
extracts of Cissus cornifolia (Baker) Splanch (Vitaceae) parts.
AB - The study was intended to explore the antioxidant potential and phytochemical
content of the ethanol and aqueous extracts of the leaf and root samples of
Cissus cornifolia (Baker) Splanch (Vitaceae) across a series of four in vitro
models. The results showed that all the extracts had reducing power (Fe(3+) -
Fe2+) and DPPH, hydroxyl and nitric oxide radical scavenging abilities to varying
extents. However, the ethanol root extract had more potent antioxidant power in
all the experimental models than other extracts and possessed a higher total
phenol content of 136.1 +/- 6.7 mg/g. The GC-MS analysis of the aqueous and
ethanol extracts of the roots indicated the presence of the common aromatic
phenolic compounds, pyrogallol, resorcinol and catechol, a fatty acid, n
hexadecanoic acid and an aldehyde, vanillin. Data from this study suggest that
both the leaves and roots of C. cornifolia possessed anti-oxidative activities
with the best anti-oxidant activity being exhibited by the ethanolic extract of
the root. The antioxidant properties of the root extracts can be attributed to
the phenolic compounds present in the extracts.
PMID- 25850208
TI - Diuretic activity of aqueous extract of Nigella sativa in albino rats.
AB - The study aims to evaluate the diuretic effect and acute toxicity of a crude
aqueous extract of Nigella sativa using animal models. To evaluate the diuretic
activity of the plant, Albino rats were divided into five groups. The control
group received normal saline (10 mL/kg), the reference group received furosemide
(10 mg/kg) and the test groups were administered different doses (i.e., 10, 30
and 50 mg/kg) of the crude extract by intra-peritoneal route, respectively. Graph
Pad Prism was used for the statistical analysis and p-values less than 0.05 were
considered statistically significant. We observed significant diuretic,
kaliuretic and natriuretic effects in the treated groups in a dose dependent
manner. However, urinary pH remained unchanged during the course of the study.
The diuretic index values showed good diuretic activity of the crude extract. The
Lipschitz values demonstrated that the crude extract, at the dose of 50 mg/kg,
showed 46% diuretic activity compared with furosemide. With regard to the acute
toxicity study, no lethal effects were observed among Albino mice even at the
higher dose of 5000 mg/kg. The extract of Nigella sativa, at the dose of 50
mg/kg, significantly increased the urinary volume and modified the concentration
of urinary electrolytes, and there was observed no signs of acute toxicity
associated with the crude extract. Further studies are encouraged to isolate the
pure phytochemical responsible for diuresis.
PMID- 25850209
TI - Antioxidant and anti-inflammatory activity of Potentilla reptans L.
AB - Potentilla species have been used in traditional medicine in the treatment of
different ailment, disease or malady. Potentilla reptans (P. reptans) has been
scarcely studied. The aim of this study was to test antioxidant and anti
inflammatory activity of P. reptans aerial part and rhizome. DPPH assay was used
to measure antioxidant activity of aqueous plant extracts. Anti-inflammatory
effect was evaluated by experimental animal model of phenol-in-acetone induced
mice ear edema. DPPH radical-scavenging activity of both tested extracts was
concentration dependent with IC50 values 12.11 MUg/mL (aerial part) and 2.57
MUg/mL (rhizome). Maximum anti-inflammatory effect (61.37%) was observed after
administration of 10 mg/ear of the rhizome extract and it was 89.24% of effect
induced by dexamethasone as a standard. In conclusion, P. reptans rhizome aqueous
extract possesses anti-inflammatory effect and higher antioxidant activity than
aerial part.
PMID- 25850210
TI - In vitro and in vivo antimicrobial evaluation of alkaloidal extracts of Enantia
chlorantha stem bark and their formulated ointments.
AB - The in vitro and in vivo antimicrobial evaluation of the formulated ointment of
alkaloidal extract of Enantia chlorantha Oliv. (Annonaceae) was the concern of
this study. The alkaloidal fraction of the stem bark extract was formulated into
simple ointment using British Pharmacopoeia formula for preparation of simple
ointment. Agar diffusion and agar dilution methods were used for the in vitro
antimicrobial studies. Ketoconazole 4000 MUg/mL and tioconazole cream 1% were
used as reference standards while normal saline was used as control. The
fungicidal activity kinetics of the plant extract was carried out using selected
concentrations of the plant extract against the most sensitive organism (Candida
albicans). For the in vivo studies, 25 albino rats weighing between 180-200 g
were divided into 5 groups, anesthesized (thiopental sodium 50 mg/kg), infected
with overnight culture of Candida albicans and incubated at 37 degrees C for
three days to allow for growth of the microorganisms. Each of the five groups was
treated on the third day of incubation with different concentrations of the
formulated simple ointment (200 mg/mL, 100 mg/kg, 50 mg/mL), tioconazole cream 1%
(reference standard) and normal saline control, respectively. The alkaloidal
extract exhibited greater zones of inhibition with Candida glabrata and
Trichophyton tonsurans while Candida albicans and Trichophyton interdigitali also
showed some sensitivity. There was no surviving organism at the end of 240 min at
100 mg/mL concentration with 10(-4) dilution factor. Treatment of the infected
rats with the formulated simple ointments (200, 100 and 50 mg/mL) showed that 50
mg/mL ointment had a better percentage reduction in the fungal loads at the end
of the experiment when compared with the 200 mg/mL simple ointment as well as the
standard tioconazole 1% cream and normal saline treated rats, respectively. The
alkaloidal fraction of Enantia chlorantha stem bark as well as the formulated
ointment exhibited significant in vitro and in vivo antifungal activities against
different species of Candida, dermatophytes and plant fungi.
PMID- 25850211
TI - Effects of white mulberry (Morus alba) leaf tea investigated in a type 2 diabetes
model of rats.
AB - The present study was aimed to investigate the anti-diabetic effects of a low
(0.25%) and a high (0.5%) dose of white mulberry leaf tea in a rat model of type
2 diabetes (T2D). Six week old male Sprague-Dawley rats were divided into four
groups: Normal control (NC), Diabetic control (DBC), Diabetic mulberry tea low
(DMTL, 0.25%) and Diabetic mulberry tea high (DMTH, 0.50%). T2D was induced by
feeding a 10% fructose solution in drinking water for 2 weeks to induce insulin
resistance, followed by a single injection (i.p.) of streptozotocin (40 mg/kg
body weight (b.w.)) to induce partial pancreatic beta-cell dysfunction in all
groups except the NC group, which only received a normal drinking water and
citrate buffer (pH 4.4) instead of fructose solution and STZ injection,
respectively. After 4 weeks feeding of brewed mulberry leaf tea, there were no
significant improvements in polyphagia, polydipsia, body weight gain, blood
glucose, glucose intolerance, serum insulin, fructosamine, AST, ALT, creatinine,
albumin and uric acid levels and liver parameters when serum total cholesterol
was significantly and LDL-cholesterol and triglyceride concentrations were
markedly decreased in the DMTH group compared to the DBC and DMTL groups. Serum
total proteins were significantly reduced in DMTL and DMTH groups compared to the
DBC group. These results suggest that brewed white mulberry leaf tea has
hypolipidemic rather than antidiabetic effects at least in this experimental
condition. However, the effects of the different brands of white mulberry leaf
tea may be varied due to various factors.
PMID- 25850212
TI - The influence of low process temperature on the hydrodynamic radius of polyNIPAM
co-PEG thermosensitive nanoparticles presumed as drug carriers for bioactive
proteins.
AB - The aim of the work was to evaluate the influence of low process temperature on
the hydrodynamic radius of the synthesized nanoparticles presumed for
incorporation of bioactive proteins. The reaction prompted in temperatures of 22,
38 and 70 degrees C. The first one reflected the ambient environmental
temperature, at which the bioactive proteins may be implemented into the reactant
mixture. The intermediate temperature should enable safe use of proteins during
the reaction, and represents the upper limit of applied heat, due to the
consequent denaturation of proteins at elevated temperatures. The reactant
mixture heated up to 70 degrees C provides excellent formation of nanoparticles,
however the albuminous components will tend to degrade. Within the study we
applied N,N,N',N'-tetramethylethane-1,2-diamine as an accelerator in the presence
of the strong oxidizing agent--ammonium persulfate as radical initiator. Six
batches of N-isopropylacrylamide derivatives with polyoxyethylene glycol
diacrylamide co-monomer of molecular weight in the range of 2000 Da were
synthesized within the course of surfactant free precipitation polymerization.
The nanodispersions were assessed in the terms of hydrodynamic radius, by the
dynamic light scattering method (DLS). The polydispersity index, as well as
average hydrodynamic radius, and hydrodynamic radius of main population of
particles, identified in the DLS device, were evaluated and discussed in the
perspective of application of the nanogels as drug carriers for bioactive
proteins.
PMID- 25850213
TI - Fast ultra-fine self-nanoemulsifying drug delivery system for improving in vitro
gastric dissolution of poor water soluble drug.
AB - Meloxicam (MLX) has poor water solubility which leads to slow absorption
following oral administration; hence, immediate release tablet is unsuitable in
the treatment of acute pain. The aim of this study was to prepare a novel fast
ultra-fine self-nanoemulsifying drug delivery system (UF-SNEDDS) of MLX for oral
administration to facilitate drug release process in the stomach as well as
comparing its in vitro dissolution with commercial Mobic and Mobitil tablets. MLX
solubility in oils, mixed glycerides and surfactants with different HLB values
was investigated. Based on MLX solubility profiles, eight UF-SNEDDSs composed of
MLX, Cremophor RH 40 as oily phase, Capmul MCM-C8 or Tween 80 as surfactant and
PEG 400 as co-solvent were prepared and evaluated for their spontaneous formation
of emulsion, droplet size, turbidity and in vitro dissolution. The prepared novel
MLX formulations showed a significant very low droplets size (up to 25 nm),
thermodynamically stable and spontaneously formed nanoemulsion. MLX UF-SNEDDS
formulations showed significant high percentage of drug dissolution (up to 70%)
in simulated gastric fluid, compared with Mobic and Mobitil. In conclusion, due
to higher drug release from MLX UF-SNEDDS formulations they could enhance its
absorption and hence its bioavailability.
PMID- 25850214
TI - Amorphous solid dispersion studies of camptothecin-cyclodextrin inclusion
complexes in PEG 6000.
AB - Abstract: The present work focused on the solubility enhancement of the poorly
water-soluble anti-cancer agent camptothecin which, in its natural state,
presents poor solubility inducing lack of activity with a marked toxicity. A new
approach is adopted by using a ternary system including camptothecin (CPT) and
cyclodextrins (CDs) dispersed in polyethylene glycol (PEG) 6000. Camptothecin
solubility variations in the presence of alpha-CD, beta-CD, gamma-CD,
hydroxypropyl-alpha-CD (HPalpha-CD), hydroxypropyl-beta-CD (HPbeta-CD), permethyl
beta-CD (PMbeta-CD) and sulfobutyl ether-beta-CD (SBEbeta-CD), were evaluated by
Higuchi solubility experiments. In the second part, the most efficient
camptothecin/P-CDs binary systems, mainly HPbeta-CD and PMbeta-CD, were dispersed
in PEG 6000. In addition to a drug release and modeling evaluation, the CPT
interactions with CDs and PEG 6000 to prepared the amorphous solid dispersion in
the binary and ternary systems were investigated by Fourier transformed infrared
spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric
analyses (TGA) and X-ray powder diffraction (XRPD). The results showed that
HPbeta-CD and PMbeta-CD were the most efficient for camptothecin solubilization
with highest apparent equilibrium constants. Dissolution studies showed that
percentage of CPT alone after two hour in 0.1 M HCI medium, did not exceed 16%,
whereas under the same conditions, CPT/PMbeta-CD complex reached 76%. When
dispersing the binary systems CPT/beta-CDs in PEG 6000, the velocity and the
percentage of CPT release were considerably improved whatever the CD used,
reaching the same value of 85%. The binary and ternary systems characterization
demonstrated that CPT inclused into the CDs cavity, replacing the water
molecules. Furthermore, a drug transition from crystalline to amorphous form was
obtained when solid dispersion is realized. The present work demonstrated that
ternary complexes are promising systems for CPT encapsulation, and offer
opportunities to use non toxic and commonly solubilizing carriers: betaCD and PEG
6000 to improve bioavailability.
PMID- 25850215
TI - Preparation and in vitro characterization of a non-effervescent floating drug
delivery system for poorly soluble drug, glipizide.
AB - The aim of the present study was to formulate a non-effervescent floating drug
delivery system of glipizide, a poorly water soluble drug. The solubility of
glipizide was initially enhanced using a solid dispersion (SD) strategy with the
help of hydrophilic carriers such as poloxamer, cyclodextrin, and povidone. The
optimized core material/SD was further formulated into non-effervescent floating
tablets (NEFT) by using matrix ballooning inducers, such as crospovidone and
release retarding agents including HPMC and PEO. Poloxamer-based solid
dispersions prepared by a solvent evaporation technique showed the highest
dissolution rate (1 : 10 drug to carrier ratio) compared with all other
dispersions. NEFT were evaluated for all physico-chemical properties including in
vitro buoyancy, dissolution, and release rate. All of the tablets were found to
be within pharmacopoeial limits and all of the formulations exhibited good
floating behavior. The formulations (F2 and F3) were optimized based on their 12
h drug retardation with continuous buoyancy. The optimized formulations were
characterized using FTIR and DSC and no drug and excipient interaction was found.
In-vitro buoyancy and dissolution studies showed that non-effervescent floating
drug delivery systems provide a promising method of achieving prolonged gastric
retention time and improved bioavailability of glipizide.
PMID- 25850216
TI - Effect of alloferon 1 on central nervous system in rats.
AB - Alloferon 1 is an insect-derived peptide with potent antimicrobial and antitumor
activity. It was isolated from blood of an experimentally infected insect, the
blow fly Callifora vicina. Synthetic alloferon 1 reveals a capacity to stimulate
activity of NK cells and synthesis IFN in animal and human models. Moreover, it
was demonstrated antiviral and antitumor activity of alloferon 1 in mice. There
are no data on influence of alloferon 1 on central nervous system. The aim of
present study was to determine an effect of alloferon 1 on rats' central nervous
system by some behavioral tests: open field test, hole test, score of rats
irritability, and determination of memory consolidation in the water maze test.
Moreover, a probable antinociceptive effect of alloferon 1 in rats was determined
by a tail immersion test and hot plate test. Experiments were performed on female
Wistar rats. Seven days before experiments, rats were anesthetized with ketamine
and xylazine and polyethylene cannulas were implanted into the right lateral
brain ventricle (i.c.v.). On the day of experiment, alloferon 1 dissolved in a
volume of 5 MUL of saline was injected directly i.c.v. through implanted cannulas
at doses of 5-100 nmol. It was found that alloferon 1 had slight effect on
locomotor and exploratory activity, induced some decrease of rat irritability and
a weak impairment of rats memory (only at the low dose of 5 nmol). On the other
hand, the higher dose of this peptide exerts significant antinociceptive effect.
Obtained results indicate that alloferon 1 do not exert any evidently toxic
effect on central nervous system in rats. Therefore, alloferon 1 may be good new
drug with antitumor and antinociceptive activity.
PMID- 25850217
TI - Variation in vitamin D plasma levels according to study load of biomedical
students.
PMID- 25850218
TI - [Claude Leclerc, from theater to mental health].
PMID- 25850219
TI - [Augustinian monastery. 375 years of nursing commitment].
PMID- 25850220
TI - [Chaudiere-Appalaches. Prevent infections in the elderly residents].
PMID- 25850221
TI - [Abitibi-Temiscamingue. Role of the nurse in isolated communities].
PMID- 25850222
TI - [Mauricie/Central Quebec. Less waiting in hemato-oncology].
PMID- 25850223
TI - [Advocacy for enhancement of clinical judgment. The Braden Scale: reactions].
PMID- 25850224
TI - [The Braden Scale: reactions (cont.)].
PMID- 25850225
TI - [PTI and DSQ].
PMID- 25850226
TI - [Vicarious trauma or compassion fatigue, beware!].
PMID- 25850227
TI - [Obstructive sleep apnea. A sleep disorder with serious consequences].
PMID- 25850228
TI - [Parkinson's disease. A delicate balance].
PMID- 25850229
TI - [Intensive care. The CPOT, assess pain of unconscious adult patients].
PMID- 25850230
TI - [SIPPE. How to maintain the loyalty of the families to the program?].
PMID- 25850231
TI - [Sterility breach in the operating room].
PMID- 25850232
TI - [Vitamin D. Even more sunshine vitamin for overweight people].
PMID- 25850233
TI - [Polymyalgia rheumatica. A higher risk of heart attack and stroke].
PMID- 25850234
TI - [Partial epilepsy: Aptiom].
PMID- 25850236
TI - [The digital polymerase chain reaction as a new technology and its potential
input in molecular diagnostic].
PMID- 25850235
TI - [The coding according molecular mass of synthetic biomarkers under comprehensive
testing of urine components: horizons of disease monitoring].
PMID- 25850237
TI - [MALDI-TOFF mass spectrometry: transformative proteomics in clinical
microbiology].
PMID- 25850238
TI - [The microprobes of antigens for studying of autoimmune diseases].
PMID- 25850239
TI - [The evaluation of sensitivity and specificity of technique of detection of C
reactive protein under diagnostic of infectious complications in patients with
acute lymphoblastic leucosis receiving chemotherapy].
AB - The C-reactive protein is a generally recognized marker of inflammation and
bacterial infection. However, issue of diagnostic effectiveness of this indicator
is still open-ended in case of patients with oncologic hematological diseases.
The level of C-reactive protein can increase under neoplastic processes. On the
contrary, the inhibition of immune response observed under cytoplastic therapy
can decrease synthesis of this protein. The study was organized to establish
levels of C-reactive protein as markers of infection in adult patients with acute
lymphoblastic leucosis under application of chemotherapy and to evaluate their
diagnostic effectiveness. The sampling included 34 patients with acute
lymphoblastic leucosis all patients had infectious complications at various
stages of treatment. The levels of C-reactive protein in groups of patients with
localized infections (mucositis, abscess, pneumonia, etc.) or fever of unknown
genesis had no statistical differences but were reliably higher in patients
without infectious complications. The concentrations of C-reactive protein in
patients with syndrome of systemic inflammatory response and sepsis had no
differences. At the same time, level of C-reactive protein under systemic
infection (syndrome of systemic inflammatory response, sepsis) was reliably
higher than in case of localized infection. The diagnostically reliable levels of
C-reactive protein were established as follows: lower than 11 mg/l--infectious
complications are lacking; higher than 11 mg/l--availability of infectious
process; higher than 82 mg/l--generalization of infection. The given levels are
characterized by high diagnostic sensitivity (92% and 97% correspondingly) and
specificity (97% and 97%) when patients receive therapy without application of L
asparaginase. At the stages of introduction of this preparation effecting protein
synthesizing function of liver sensitivity of proposed criteria are decreased
(69% and 55% correspondingly). However; due to high specificity (100% and 96%)
their diagnostic effectiveness remains high.
PMID- 25850240
TI - [The application of eosin and propidium iodide in evaluation of vitality of human
spermatozoa].
AB - The article analyzes comparative assessment of vitality of spermatozoa by
condition of permeability of membranes for eosin and propidium iodide and
comparison of results acquired using technique of light and fluorescent
microscopy. The comparison of data of light microscopy with eosin staining with
data of fluorescent microscopy with propidium iodide staining demonstrated that
percentage of content of spermatozoa separated from ejaculates of 28 fertile
males and stained with eosin was reliably higher (34.8 +/- 3.2) than percentage
of content of spermatozoa with stained with propidium iodide (2.1 +/- 4.0). After
incubation of spermatozoa under room temperature during 24 hours percentage of
unviable cells with stained eosin also was higher than in case of propidium
iodide staining correspondingly (44.5 +/- 3.3% and 34.7 +/- 3.6%). The analysis
of vitality of spermatozoa under damaging effect of oxidative stress on cell
membrane developed by 4 hours incubation with 200 mkM of hydrogen peroxide (H2O2)
demonstrated that under staining of spermatozoa with propidium iodide
significantly higher percentage of damaged cells is detected. In such cases,
eosin staining is less suitable for detection of vitality of spermatozoa (73.6 +/
5.8% against 51.7 +/- 6.4%). The carried out experiment demonstrates that in
case of detected effects on spermatozoa (for example, effect of oxidative stress)
the light microscopy insufficiently adequate reflects degree of damage of
membranes of spermatozoa. The fluorescent microscopy detects a higher percentage
of spermatozoa with damaged membrane.
PMID- 25850241
TI - [The prognostic value of evaluation of minimal residual disease using technique
of flow cytofluorometry during application of therapy of chronic lymphatic
leukemia].
AB - The achievement of molecular remission is associated with increasing of survival
of patients with chronic lymphatic leukemia. The important direction of research
is seeking of parameters applicable to forecast of response to therapy. The
purpose of the study was evaluating prognostic significance of indicator of
minimal residual disease detected by technique of flow cytofluorometry of
peripheral blood of patients with chronic lymphatic leukemia during therapy
application. The sampling included 112 patients with chronic lymphatic leukemia
aged from 43 to 82 years. All patients were given treatment consisted of 6
courses of immune chemotherapy combined with fludarabine with cyclophosphan and
rituximab. The samples of peripheral blood were analyzed after 3 courses during
therapy and after 6 courses after completion of treatment. The cells were
analyzed using 5 and 6 color flow cytometry for the purpose of detection of
immune phenotype associated with chronic lymphatic leukemia. The evaluation of
minimal residual disease was implemented according international standardized
protocol (Rawstron A.C. et al. 2007; 21 (5): 956-64). The minimal residual
disease negative status was reached in 87 (78%) patients during evaluation of
response after 6th course of treatment. The implementation of indicators of
residual disease after 3 courses with fludarabine, cyclophosphan and rituximab
permitted to sort out two groups of patients with chronic lymphatic leukemia i.e
67 patients with low (< 0.12%) level of minimal residual disease and 45 patients
with high (> 0.12%) level of tumor cells. The rate of molecular remission after
completion of treatment. in the given groups consisted 100% and 44%
correspondingly. The study demonstrates possibilities of early immune phenotype
evaluation of minimal residual disease to forecast differences in response to
treatment in patients with chronic lymphatic leukemia that makes it possible to
avoid undesirable toxicity of therapy or to choose method of consolidation.
PMID- 25850242
TI - [The cytological diagnostic of adenocarcinoma of pancreas with technique of size
separation of tumor cells circulating in peripheral blood (case report)].
AB - The diagnostic of tumor cells circulating in blood is one of most perspective and
actively developing directions in cytology. The most of proposed techniques for
this purpose are based on using immune cytochemical or molecular genetic modes to
characterize cells. At the samne time, growing spread receives technique of
separation of circulating tumor cells based on their larger size in comparison
with other blood cells (ISET). The article presents clinical monitoring of
application of mentioned technique to verify diagnosis and onset of treatment in
female patient with reiterated ineffective diagnostic punctures of pancreas.
PMID- 25850243
TI - [The effect of prolonged flow aspiration drainage of laparotomy wounds of
oncological coloproctologic patients on cytological parameters of wound
secretion].
AB - In oncologic coloproctologic patients the comparative cytological analysis of
wound secretion in healing midline laparotomy wounds was implemented. The wounds
were taken in common way (layer-by-layer tightly) and with prolonged flow
aspiration drainage of subcutaneous cellular tissue. It is proved that
application of prolonged flow aspiration drainage effects positively on
regeneration process and objectively reflects more benevolent course of healing
of laparotomy wounds. In the end, this mode decreases number of festering from
7.3% in control group to 1.6% in main group (p < 0.05).
PMID- 25850244
TI - [The count of urine corpuscles using automated analyzer Iris IQ 200 TM].
AB - The volume of urine of high power field of analyzer Iris IQ 200 TM was identified
according standard of stabilizing erythrocytes and amounted up to 0.18 mkl. The
amount of urine corpuscles detected by analyzer in this volume corresponds to
amount of urine corpuscles under microscopy of sediment often times concentrated
urine at thickness of preparation in 0.1 mm, under microscope with objective x40
and ocular 10/18. The count of corpuscles by analyzer in 1 mkl of urine is the
most objective and convenient technique for quantitative evaluation of urine
corpuscles.
PMID- 25850245
TI - [The diagnostic of defects of inborn immunity under B-cell tumors of lymphatic
system].
AB - The genetic characteristics are key risk factors of development of many human
neoplasms including B-cell tumors of lymphatic system. The relationship between
polymorphic variants of genes FCGR2A (His 1 66Agr), CD14 (C-159T). IL1beta (T
31C), IL2 (7:330G) and 7LR2 (Arg753Ghn) and development of various forms of B
cell tumors of lymphatic system in 80 patients was investigated. The
statistically significant differences of rates of particiular genotypes of single
nucleotid polymorphisms of genes FCGR2A, CD14. IL1beta, IL2 and TLR2 in patients
with indolent and aggressive types of course of non-Hodgkin lymphoma and also
multiple myeloma. The results prove hypothesis that genetic variants of genes of
inborn immune response effect the origin and character of course of different
types of lymphoproliferative diseases. The markers can become additional
prognostic characteristics of benign and aggressive course of tumors.
PMID- 25850246
TI - [The antibodies to neurohormonal anti-genes as a criterion of early diagnostic
and neurointoxication in workers of chemical enterprises].
AB - The examination was applied to enterprise workers laboring in conditions of vinyl
chloride (79 patients), caustic soda (24 patients) and 10 patients with
professional chronic mercury intoxication. The differences are established
concerning manifestation of autoimmune reactions of personnel working in
conditions of chronic effecting of vinyl chloride distinct of parameters
characterizing autoimmune reactions of personnel working under impact of another
neuro-toxicants (vapors of metallic mercury). The increasing of auto-antibodies
to MAG was detected in healthy personnel and increasing of concentrations of auto
antibodies to protein S-100 and DNA was detected in personnel with initial
manifestations of neuro-intoxication. These occurrences testify availability, of
different mechanisms underlying formation of neurological disorders. The study
data confirms involvement of auto-antibodies to neuronal antigens into
derangement of neural activity in personnel working in conditions of effect of
vinyl chloride and vapors of metallic mercury. Hence, the new possibilities are
opened in studying pathogenesis of occupational neuro-intoxications. The
detection of auto-antibodies to proteins of neural tissue can be recommended as a
criterion of early identification of damage of neural system in personnel working
in conditions of chemical industry.
PMID- 25850247
TI - [The prognostic significance of particular immunological indicators of lachrymal
fluid in patients using soft contact lenses].
AB - The study was carried out to identify concentrations of vessel epithelium growth
factor (VEGF), souble forms of VEGF receptor type I and II, chemo-toxic protein I
and metalloproteinase-9 in lachrymal fluid. The immune enzyme analysis was
applied. He sampling included patients with myopia without complications while
using silicone hydro-helium and hydro-helium contact lenses and patients with
hypoxic complications of contact correction. It is established that application
of hydro-helium and silicone hydro-helium contact lenses more than one year is
followed by increasing of concentration of detected substances in lachrymal
fluid. Under hypoxic complications of contact correction the levels of substances
are significantly higher than in cases without complications. This occurrence
makes it possible to substantiate possibility of application of immunologic
indicators as diagnostic markers.
PMID- 25850248
TI - [The separation, identification and molecular biologic analysis of isolates of
pandemic influenza virus A(H1N1)pdm09].
AB - The article presents data concerning analysis of bioassays under suspicion of
influenza A(H1N1)pdm09. The technique of back transcription polymerase chain
reaction and sequencing was applied. The separation of native influenza virus A
was implemented using passaging through developing chick embryos.
PMID- 25850249
TI - [The formation of bio-films by opportunistic microorganisms isolated from
patients with rheumatic diseases].
AB - The study was carried out concerning capability of 194 strains of opportunistic
microorganisms to form bio-films. It is established that bacteria ecizing
organism of patients with rheumatic diseases have capacity to form microbial bio
films. The formation of bio-films is manifested with the same rate as in agents
of inflammatory processes. At that, Escherichia coli, Staphylococcus haemolyticus
and bacteria of genus Proteus isolated under rheumatic diseases have
significantly higher capability to form biofilms that matters for development of
comorbide infections.
PMID- 25850250
TI - [The detection of strains of Esherichia coll producing Shiga toxin in populations
of normal intestinal microbiota in children with functional disorders of
gastrointestinal tract].
AB - In intestinal ecosystem, interchange of genetic material between different types
of bacteria and other representatives of family Enterobacteriaceae results in
development of types of normal colibacillus with genetic characteristics of
pathogenicity. This occurrence can be considered as a theoretical substantiation
for labeling such strains as pathobionts. The polymerase chain reaction was
implemented to analyze 96 strains of different types of Escherichia coli (with
normal and weak zymogenic activity and hemolytic activity) isolated from children
with functional disorders of gastrointestinal tract. The purpose was to detect
presence of gens coding capacity of toxin production (six1, stx2). In intestinal
biotope of children, circulation of strains of Escherichia coli producing shiga
toxin having no relation to pathogenic group being representatives of normal
indigenous microbiota. The presence of gens stx1 and stx2 in various biochemical
types of Escherichia coli permits establishing fact of forming of reservoir of
potential pathogenicity in non-pathogenic forms of Escherichia coli. The presence
of gen (verotoxin 1) in genome of various types of Escherichia coli isolated from
one single biotope testifies possible horizontal transmission of factors of
pathogenicity in intestinal biotope.
PMID- 25850252
TI - [Community characters of Lophatherum gracile in Yongchuan district of Chongqing].
AB - To understand Lophatherum gracile plant community's structural characteristics, a
survey of community structure and species diversity was conducted through quadrat
sampling in Yongchuan district of Chongqing. The results showed that there were
386 species vascular plants, belonging to 117 families and 229 genera. Based on
habitat, community structure and species composition, L. gracile were found in
three community types: Pinus massoniana community, banboo community, shurb
community. Vertical structure was composed of three layers, including tree layer,
shrub layer and herb layer. Species in shrub layer was the richness. P.
massoniana is the only dominant species of the community, it can not regenerate
naturally, the shrub layer has a greater effect on the community of L. gracile in
the future. In addition, the banboo community and shurb community is not stable
because of human's activity. Therefore, the community characters of L. gracile
should be taken care of conservation when the resources are utilized.
PMID- 25850251
TI - [The quantitative testing of V617F mutation in gen JAK2 using pyrosequencing
technique].
AB - The somatic mutation V617F in gen JAK2 is a frequent cause of chronic
myeloprolific diseases not conditioned by BCR/ABL mutation. The quantitative
testing of relative percentage of mutant allele can be used in establishing
severity of disease and its prognosis and in prescription of remedy inhibiting
activity of JAK2. To quantitatively test mutation the pyrosequencing technique
was applied. The developed technique permits detecting and quantitatively,
testing percentage of mutation fraction since 7%. The "gray zone" is presented by
samples with percentage of mutant allele from 4% to 7%. The dependence of
expected percentage of mutant fraction in analyzed sample from observed value of
signal is described by equation of line with regression coefficients y = - 0.97,
x = -1.32 and at that measurement uncertainty consists +/- 0.7. The developed
technique is approved officially on clinical material from 192 patients with main
forms of myeloprolific diseases not conditioned by BCR/ABL mutation. It was
detected 64 samples with mautant fraction percentage from 13% to 91%. The
developed technique permits implementing monitoring of therapy of myeloprolific
diseases and facilitates to optimize tactics of treatment.
PMID- 25850253
TI - [Effect of total ginsenosides on protective enzymes of Mythimna separata larvae].
AB - Under indoors simulating natural growing condition, the 4th-instar Mythimna
separata larvae were fed by using poi- son leaf disk method. The effect of total
ginsenosides on the protective enzymes (PPO, T-SOD, CAT and POD) of M. separata
larvae was studied. The total ginsenosides could influence the protective enzymes
of 4th-instar M. separata larvae significantly. After treated by total
ginsenosides, the PPO activities increased firstly then decreased, and tended to
equilibrium, and reached the maximum after 48 h. Furthermore, the total
ginsenosides disturbed the dynamic balance of SOD, CAT and POD of M. separata
larvae, and the yield of O2-* speeded. The results suggest that the total
ginsenosides influence the protective enzymes of 4th-instar M. separata larvae,
and disturb the original dynamic balance of protective enzymes. Consequently the
insect suffers from the harm of O2-*.
PMID- 25850254
TI - [Isolation of endophytic fungi from Macleaya cordata and screening of
sanguinarine-producing strains].
AB - Endophytic fungi were isolated from Macleaya cordata growing in Dabie Mountain by
agar-block method, and then the endophytic fungi were grouped into different
types based on their morphological characteristics, and thin layer chromatography
(TLC) and high performance liquid chromatography (HPLC) were employed to
determine whether the metabolic substances contained sanguinarine or not, and
then preliminarily identified by morphological method. The results showed that
the leaves hosted the largest number of endophytes (96 isolates) followed by the
stems (57 isolates) and finally the roots (28 isolates), respectively. Based on
morphological characteristics the endophytic fungi were grouped into 26 types in
our study. TLC and HPLC results showed that there was sanguinarine in the
metabolic substances of BLH 51 strain. According to the morphological
characteristic, the BLH 51 strain was identified as Fusarium proliferatum. All
these indicated that the medicinal plant M. cordata harbors abundant endophytes,
which could be a new source for the search of active secondary metabolites.
PMID- 25850255
TI - [Study on preferred food of adult Mylabris phalerata in different geographical
populations].
AB - With the deterioration of environment, and the excessive collection of wild
resources, the wild populations of Myla- bris phalerata Pallas are less and less,
almost extincted in many traditional distribution areas. It is necessary to breed
M. phalerata artificially for sustainable utilization. Food preference of adult
M. phalerata is the key to its provenance screening and domestication in the
artificial breeding. In this paper, the food preference of 3 geographical
populations of M. phalerata was studied. The results showed that the food
preferences of adult M. phalerata in different geographical populations were
different. The adult M. phalerata in Wuming preferred cucumber flowers, gourd
flowers and melon flowers. The adult M. phalerata in Tianlin preferred cowpea
flowers. And the adult M. phalerata in Guangzhou preferred cowpea flowers and
gourd flowers. Gourd flowers were the most attractive food for the adult M.
phalerata of 3 geographical populations of M. phalerata.
PMID- 25850256
TI - [Effect of combined application of zinc, boron and molybdenum on yield and
saikosaponin a, saikosaponin d contents of Bupleurum chinense].
AB - This research use "3414" fertilizer effect experiments to handle zinc, boron and
molybdenum trace element fertilizer, determined the dry matter accumulation and
content of saikosaponion a and d, to investigate the different ratio of zinc,
boron and molybdenum on yield and saikosaponin a, saikosaponin d contents of
Bupleurum chinense. Found The suitable ratio of zinc, boron and molybdenum play
an active role on dry matter accumulation and distribution, the treatment
Zn2B2Mo3 is the best one to promote the dry matter accumulation and transfer to
the underground part; in a certain range, only use zinc or molybdenum can promote
the yield of B. chinense, the yield of treatment Zn2B2Mo1 is the highest one.
According to the results of regression analysis: in accordance with Zn 48.45 g x
hm(-2), B 355.05 g x hm(-2), Mo 86.40 g x hm(-2), can obtain the yield with
3313.05 kg x hm(-2); the treatment Zn2BMo2 is most effective to promote the total
saikosaponin a and d accumulated, according to the results of regression
analysis: in accordance with Zn 36.15 g x hm(-2), B 343.05 g x hm(-2), Mo 106.35
g x hm(-2), the content of total saikosaponin a and d can reach 1.23%. This
research first discovered the suitable ratio of zinc, boron and molybdenum can
promote the yield and saikosaponin a, saikosaponin d contents on B. chinense.
PMID- 25850257
TI - [Differences of fungal diversity and structure in rhizosphere of Fritillaria
thunbergii from different provenances].
AB - To explore the mechanism of soil microbial ecology, the differences of fungal
diversities in rhizosphere of different provenances of Fritillaria thunbergii
were analyzed. The diversities and compositions of rhizo-fungi of the samples
were analyzed by using DGGE and 454 pyrosequencing. DGGE results showed the
Shannon index of Ninbo provenance planted in Ninbo was the highest one. And its
dominant fungi were Ascomycota, Deuteromycota and Zygomycota. Except the same
fungi, every provenance planted in Ninbo had its own special ones. From the 454
pyrosequencing, the fungal diversity in Panan producing was the highest which was
similar with DGGE result. Among the ten phylum detected in its rhizosoil,
Fungi_incertae_sedis, Ascomycota, Mucoromycotina, Basidiomycota and
Chytridiomycota almost amounted to 90% of the whole community. The fungal types
and amounts in Panan were more than those in Ninbo indicating the differences
between producing areas and the advantage of macro genome sequencing. There were
10 phyla, 29 families, 28 genus and 159 species of fungi in Panan provenance, 6
phyla, 20 families, 19 genus, 136 species in Ninbo provenance, 8 phyla, 37
families, 47 genus, 289 species in Nantong provenance and 7 phyla, 25 families,
24 genus, 102 species in the bulk soil. Some genus such as Dothidea,
Capnobotryella and Conidiobolus were only existed in Nantong provenance, while
Pyrenochae- ta, Glomus and Pseudonectria were only in Panan provenance, which
implied these species could grew because F. thunbergii influenced the existence
of fungi. Experiments of provenance and producing area of F. thunbergii showed
that the fungal diversity of indigenous provenance was higher than that of exotic
provenance and each provenance had unique fungal species in the rhizosphere,
which indicated that the diversity and structure was shaped cooperatively by the
species and soil type. These fungal species are interacted with the soil
rhizhosphere-microbe microecological system, which in turn influence the growth
of F. thunbergii.
PMID- 25850258
TI - [Research on life history and phenological period of wild-stimulated cultivated
Gastrodia elata f. elata in Guizhou].
AB - In order to get to know the imitation of wild Gastrodia elata in life history and
phenology period, by G. elata f. elata forest wild simulated cultivation in
Dafang county, Guizhou province, observing and recording its morphological
characteristics of each growth and development stage. This experiment summarized
the law of its life history over 24 months, amplified the characteristics of each
5 phenology periods over the sexual and asexual reproduction of wild simulated
cultivated G. elata f. elata in Guizhou. Which the results could clear the
process of wild simulated cultivated G. elata f. elata in Guizhou, and provide a
theoretical support for the standard technical of the simulated wild G. elata.
PMID- 25850259
TI - [Correlations between micromeritic properties of mixing powders of danshen
extract and formability of their pellets].
AB - It was difficult to prepare traditional Chinese medicine pellets due to the
adverse characteristics of the herbal extract. In this study, Danshen extract
(DS) powder mixed with different proportions of microcrystalline cellulose (MCC),
lactose and starch were made into pellets by extrusion-spheronization. Particle
size, span, bulk density, tapping density, compressibility, Hausner ratio and
angle of repose were used to evaluate the micromeritic properties of mixing
powders. Feret diameter, aspect ratio, yield, density and friability were used to
evaluate the properties of the pellets. The correlations between micromeritic
properties of raw material powders and the formability of their pellets were
analyzed by cluster analysis, principal component analysis and partial least
squares regression analysis. As a result, the particle size of the powders was
negatively correlated with the size, density, yield, and was positively
correlated with the friability of their pellets. The span, density,
compressibility and angle of repose of the powders were positively correlated
with the size, density, yield, and were negatively correlated with the friability
of their pellets. So there were certain correlations between the micromeritic
properties of raw material powders and the properties of their pellets prepared
by extrusion-spheronization. This research provided a foundation for the
technology and method of traditional Chinese medicine extract pellets.
PMID- 25850260
TI - [Research on stability of melittin in different solvent systems].
AB - The stability of melittin in different solvents (water, deoxygenated water,
physiological saline, PBS, 50% ethanol, ethanol, glycerol)was studied and the
results showed that the stability of melittin is not influenced by light,
temperature and pH in 50% ethanol, which melittin can be completed dissolved when
compared with ethanol and glycerol, in such, 50% ethanol was chosen as solvent
storage when measured content of melittin. Then the effect of different
concentrations of PBS, the pH of PBS and rat skin ho- mogenates were tested, and
the results showed that melittin was degraded rapidly at low concentration
solution and low ionic strength. Increasing pH of PBS and rat skin homogenate can
accelerate the degradation of melittin. These researches provide an experimental
ba- sis for further study of melittin.
PMID- 25850261
TI - [Studies on new co-processed excipient consisting of lactose and gelatinized
starch].
AB - Co-processed excipients withgelatinized or non-gelatinized starch were prepared
by spray drying. Powder and tablet properties of corocessed excipients prepared
were compared with those of physical mixtures and spray-dried lactose. Their
applicability in traditional Chinese medicine (TCM) powder tableting was tested
on two TCM extracts, i.e., the gardenia extract and the Herba Sedi extract. It
was shown that gelatinizing starch before co-spray drying with lactose could
improve the performance and efficiency of starch as a binder, resulting in
remarkable improvement in physicomechanical properties of co-processed excipients
prepared. Conpared to self-made and commercially available spray-dried lactose,
co-processed excipients achieved better compactability and higher drug loading
for TCM extracts. In conclusion, the lactose-gelatinized starch co-processed
excipient, with excellent physicomechanical properties, is promising to be
explored as a new excipient for direct tableting.
PMID- 25850262
TI - [Selecting solvent and solubilizer for puerarin nasal drops by solubility and
irritation].
AB - In order to test the equilibrium solubility of puerarin in different solvents and
solubilizer,cilia toxicity and irritation of these excipient, the balance method,
toad in the ciliary body toxicity and rat nasal mucosa irritation were used
respectively. Results showed that puerarin solubility was 56.44 g x L(-1) in
combined solvent of 30% PEG200 and 10% Kolliphor HS 15. With normal saline
solution as negative control and sodium deoxycholate as positive control, the
effects of 30% PEG200, 30% PEG 400, 10% Kolliphor HS 15 and combination of 30% of
PEG200 and 10% Kolliphor HS 15 on toad palate cilium were observed and cilia
movement duration was recorded. The results indicated that there was no
significant difference in cilia movement duration among 30% PEG200, 10% Kolliphor
HS 15 and normal saline group. The rats long-term nasal mucous membrane
irritation of 30% PEG 400, 10% Kolliphor HS 15, which had no cilia toxicity, was
studied, with normal saline solution as negative control. There were no
significant difference revealed on rat nasal mucosa epithelial thickness among
30% PEG 400, 10% Kolliphor HS 15 and normal saline. Above researches showed 30%
PEG 400, 10% Kolliphor HS 15 was ideal for solubility of puerarin nasal drops and
showed a lower cilia toxicity and irritation, and can be used as the solvent and
solubilizer of puerarin nasal drops.
PMID- 25850263
TI - [Study on absorbing volatile oil with mesoporous carbon].
AB - Clove oil and turmeric oil were absorbed by mesoporous carbon. The absorption
ratio of mesoporous carbon to volatile oil was optimized with the eugenol yield
and curcumol yield as criteria Curing powder was characterized by scanning
electron microscopy (SEM) and differential scanning calorietry (DSC). The effects
of mesoporous carbon on dissolution in vitro and thermal stability of active
components were studied. They reached high adsorption rate when the absorption
ratio of mesoporous carbon to volatile oil was 1:1. When volatile oil was
absorbed, dissolution rate of active components had a little improvement and
their thermal stability improved after volatile oil was absorbed by the loss rate
decreasing more than 50%. Absorbing herbal volatile oil with mesoporous carbon
deserves further studying.
PMID- 25850264
TI - [Chemical mechanisms involved in slow fire processing and pulverization of
Brassica juncea].
AB - This article dealed with the effects of processing method and duration on the
major bioactive components (sinigrin and sinapine thiocyanate) in Brassica
juncea. The contents of sinigrin and sinapine thiocyanate in decoctions of raw
and processed B. juncea were determined and compared by high performance liquid
chromatography on a Alltima C18 column (4.6 mm x 250 mm, 5 microm) at 35 degrees
C with the acetonitrile-0.1% phosphoric acid as the mobile phrase in gradient
elution. The detection wavelength of sinigrin and sinapine thiocyanate was set at
227 nm and 326 nm, and the flow rate was 1.0 mL x min(-1). It was found that with
the extended processing duration, the contents of sinigrin and sinapine
thiocyanate first increased and then decreased: i.e., 0-2 minutes they increased
gradually (for sinigrin, by 9.65% in processed products and 356. 10% in powder;
for sinapine thiocyanate, by 12.82% in processed products and 3.41% in powder),
and achieved their highest content at 2 min; then, decreased during the next 5
minutes (for sinigrin, by 80.35% in processed products and 82.09% in powder; for
sinapine thiocyanate, by 14.29% in processed products and 17.54% in powder),
suggesting that processing duration could significantly affect the contents of
bioactive components in B. juncea, enzymatic hydrolysis of sinigrin when the seed
is crushed in the present of moisture may be responsible for the content change.
It is recommended that the slow fire should be the best processing method and the
raw seed could be used directly in the water extracts related industrial
production.
PMID- 25850265
TI - [Study on content variation of gallic acid and ellagic acid in course of
processing of charred Granati Pericarpium].
AB - The method for determining the content of gallic acid and ellagic acid in Granati
Pericarpium was established by HPLC. Using the method, the content of raw and
charred Granati Pericarpium was determined. By comparison, it was found that the
content of gallic acid and ellagic acid increased first and then reduced during
processing. When processed on an appropriate degree, the content reached the
maximum. The result indicated that gallic acid and ellagic acid can be used as
indicators to control the processing degree of charred Granati Pericarpium.
PMID- 25850266
TI - [Investigation on chemical constituents of processed products of Eucommiae
Cortex].
AB - According to the 2010 Chinese pharmacopeia, salt processed and charcoal processed
Eucommiae Cortex were pre- pared. HPLC-DAD analysis of the content of the bark
and leaf of Eucommiae Cortex showed that the bark of Eucommiae Cortex mainly
contained lignans such as pinoresinol glucose and iridoid including genipin,
geniposide, geniposidic acid, while the leaf of Eucommiae Cortex consisted of
flavonoids such as quercetin and phenolic compound such as chlorogenic acid. The
content of pinoresinol diglucoside in the bark of Eucommiae Cortex was about 18
times more than that in the leaf of Eucommiae Cortex. The content of pinoresinol
diglucoside in salted and charcoal processed Eucommiae Cortex decreased
approximately by 30% and 85%, respectively. The content of genipin, geniposide
and geniposidic acid in the bark of Eucommiae Cortex was about 3 times, 23 times,
28 times more than that in the leaf of Eucommiae Cortex. The content of genipin,
geniposide and geniposidic acid in salted Eucommiae Cortex were reduced by 25%,
40% and 40%, respectively. The content of genipin, geniposide and geniposidic
acid in charcoal processed Eucommiae Cortex were reduced by 98%, 70%, 70%,
respectively. The content of caffeic acid in bark of Eucommiae Cortex was about 3
times more than that in the leaf of Eucommiae Cortex. The content of caffeic acid
was decreased by about 50% in the salted Eucommiae Cortex. While the content of
caffeic acid in charcoal processed Eucommiae Cortex was decreased approximately
75%; the content of chlorogenic acid in bark of Eucommiae Cortex was about 1/6 of
that in the leaf of Eucommiae Cortex. The content of chlorogenic acid in salted
and charcoal processed Eucommiae Cortex decreased by 40% and 75%, respectively;
the content of quercetin in bark of Eucommiae Cortex was only 1/40 of that in the
leaf of Eucommiae Cortex. The content of quercetin in salted and charcoal
processed Eucommiae Cortex were reduced by 60% and 50%, respectively.
PMID- 25850267
TI - [Coumarins from Leonurus japonicus and their anti-platelet aggregative activity].
AB - Chemical constituents of Leonurus japonicus were isolated and purified by a
combination of various chromatographic techniques including column chromatography
over silica gel, Sephadex LH-20, MCI, and Rp C18. Structures of the isolates were
determined by spectroscopic analysis as 10 coumarins: bergapten (1), xanthotoxin
(2), isopimpinellin (3), isogosferal (4), imperatorin (5), meransin hydrate(6),
isomeranzin(7), murrayone(8) , auraptenol(9), and osthol(10). In addition to
compound 9, the others were isolated from the genus Leonurus for the first time.
In the in vitro assay, compounds 4 and 8 significantly inhibited the abnormal
increase of platelet aggregation induced by ADP.
PMID- 25850268
TI - [Studies on flavonoids from stems of Nelumbo nucifera Gaertn and their cytotoxic
activities].
AB - This research is to investigate study the flavonoids from stems of Nelumbo
nucifera and the cytotoxic activities of iso- lated compounds. The constituents
were separated by column chromatography,and their structures were elucidated by
spectroscopic data analyses. The isolated compounds were evaluated for cytoxic
activities by MTT method. Twelve compounds were isolated and identified as
rhamnazin-3-O-beta-D-glucopyranoside (1), luteolin-3', 4'-dimethylether-7-O-beta
D-glucoside (2), kaempferol-3-O-beta-D-xylopyranosyl-(1-->2)-O-beta-D
glucopyranoside (3), quercetin-3,3'-di-O-beta-D-glucopyranoside (4), 1, 8
dihydroxy-3,7-dimethoxyxanthone (5), isorhamnetin-3-O-beta-D-glucopyranoside(6) ,
kaempferol(7), isorhamnetin (8), quercetin(9), astragalin(10), hyperoside (11)
and 1-hy- droxy-3,7,8-trimethoxyxanthone(12). All compounds were isolated from
stems of this plant for the first time, and compounds 1-5 were firstly isolated
from the family nelumbonaceae. Compounds 24 and 6 showed significant cytotoxic
activities against BEL-7402 carcinoma cell lines at a concentration of 1 x 10(-5)
mol x L(-1) with the inhibitory rate of 67.36%, 53.25%, 57.78%, 60.13% and
52.11%, respectively.
PMID- 25850269
TI - [Qualitative and quantitative analysis of major constituents in Tetrastigma
hemsleyanum by HPLC-Q-TOF-MS and UPLC-QqQ-MS].
AB - A qualitative analytical method of liquid chromatography coupled with quadrupole
time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS) was developed for
identification of multi-constituents and an analytical method was developed for
simultaneously determining 4 major compounds (rutin, isoquercitrin, kaempferol-3
0-rutinoside, and astragalin) in Tetrastigma hemsleyanum Diels et Gilg. The HPLC
Q-TOF-MS assay was performed on a Welch Ultimate XB-C18 column (4.6 mm x 150 mm,
5 microm) with the mobile phase consisting of acetonitrile (A) and water
containing 0.1% Formic acid (B) in gradient mode at a flow rate of 0.8 mL x min(
1). The column temperature was at 30 degrees C, and negative ion mode was used
for TOF-MS. The UPLC-QqQ-MS assay was performed on a Waters CORTECS C18 (2.1 mm x
100 mm, 1.6 microm) with the mobile phase consisting of acetonitrile (A) and
water containing 0.1% formic acid (B) in gradient mode at a flow rate of 0.25 mL
x min(-1). The column temperature was at 45 degrees C, and MRM mode was used for
QqQ-MS. Based on the retention time and MS spectra, 24 compounds were identified
or tentatively characterized by comparing with reference substances or
literatures. For quantitative the linear range of 4 detected compounds were good
(r > 0.9966), and the overall recoveries ranged from 98.27% to 101.58%, with the
RSD ranging from 3.15% to 5.88%. The results indicated that new approach conbined
HPLC-Q-TOF-MS and UPLC-QqQ-MS was applicable in qualitative and quantitative
quality control of Tetrastigma hemsleyanum.
PMID- 25850270
TI - [Simultaneous determination of seven constituents in Lamiophlomis rotata by
HPLC].
AB - OBJECTIVE: To establish a new method for simultaneous determination of
shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methylester,
forsythiaside B, rutin, acteoside and galuteolin in Lamiophlomis rotata. METHOD:
Separation was performed on a Welchrom-C18 chromatographic column with
acetonitrile-0.1% orthophosphoric acid as mobile phasewith gradient elution. The
flow rate was 1.0 mL x min(-1). The column temperature was 30 degrees C, and the
detection wavelength was set at 238 nm, 330 nm and 350 nm. RESULT: The seven
compounds were well separated with good linear correlations. The mean recoveries
of seven compounds were 96.47%-102.2% (RSD 0.70%-2.2%). CONCLUSION: There were
good correlations among the seven compounds in the samples of aerial parts. The
mean sum of shanzhiside methyl ester and 8-O-acetyl shanzhiside methylester in
samples of aerial parts is 1.44%. The aerial parts have more kinds of composition
and with higher content than that of underground parts in L. rotata, which was
reasonable for the resonable use of the aerial part as medicinal part. The method
was simple, repeatable and stable, which could be used for identification and
quality evaluation of L. rotata.
PMID- 25850271
TI - [Determination of five triterpenic acids from Salvia chinensis of different parts
by RP-HPLC-PDA].
AB - OBJECTIVE: To establish a RP-HPLC-PDA method for determination of five
triterpenic acids (pomolic acid, hawthorn acid, corosolic acid, oleanolic acid
and ursolic acid) in different parts of Salvia chinensis. METHOD: The isocratic
elution and separation was achieved on a Kromasil C18 column (4.6 mm x 250 mm, 5
microm), using acetonitrile-water (90:10) as the mobile phase at a flow rate of
0.8 mL x min(-1). The detection wavelength and column temperature were set at 205
nm and 28 degrees C, respectively. RESULT: The calibration curves of pomolic
acid, hawthorn acid, corosolic acid, oleanolic acid and ursolic acid were linear
over the ranges of 0.096 0-2.400, 0.1230-3.075, 0.2420-6.050, 0.2830-7.075 and
0.2730-6.825 microg (r = 0.9998, 0.9997, 0.9999, 0.9995, 0.9999), respectively.
The average recoveries were 98.43%, 98.13%, 100.6%, 98.19% and 99.15%%,
respectively, with RSD (n=6) being 1.3%, 0.67%, 1.2%, 0.87% and 0.43%.
CONCLUSION: The proposed method is so simple and highly reproducible that it
promises to be applicable for determination of major triterpenic acids in S.
chinensis.
PMID- 25850272
TI - [Research on correlation between odor and chemical compounds of Lonicera
japonica].
AB - This study aims to investigate the relationship between odor and contents of the
chemical compounds in Lonicera japonica, including chlorogenic acid, galuteolin
and polyphenols. High performance liquid chromatography (HPLC) was applied to
determine the contents of chlorogenic acid and galuteolin in L. japonica. The
ponptent of polyphenols was determined by UV-Vis Spectrophotometry. Electronic
nose was used to extract and measure the odor of L. japonica. Then SPSS 17.0
software was employed for data processing. There is a significant positive
correlation between the comprehensive index value of aroma and the contents of
chlorogenic acid and polyphenols. The regression equations have been established.
However, the relationship between the comprehensive index value and the content
of galuteolin is not obvious. This is proof that the odor of L. japonica has
close connection with the chemical compounds. Therefore, this research offered a
new method for initially determine or predict the content of the chemical
composition in L. japonica,
PMID- 25850273
TI - [Spectrum-effect relationship of Moutan cortex against lipopolysaccharide-induced
acute lung injury].
AB - This research is to study the relationship between HPLC fingerprints of Moutan
Cortex, Paeoniae Radix Rubra and Paeoniae Radix Alba and their activity on
lipopolysaccharide-induced acute lung injury. HPLC fingerprints of each extract
of Moutan Cortex,Paeoniae Radix Rubra and Paeoniae Radix Alba were established by
an optimized HPLC-MS method. The activities of all samples against protein and
tumor necrosis a factor were tested by the model of lipopolysaccharide-induced
acute lung injury. The possible relationship between HPLC-MS fingerprints and the
activitieswere deduced by the Partial least squares regression analysis method.
Samples were analyzed by HPLC-MS/MS to identify the major peaks. The results
showed that each sample had some effect on acute lung injury. Four components
with a lager contribution rate of efficacy were calculated by the research of
spectrum-effect relationship. Moutan Cortex exhibited good activity on acute lung
injury, and gallic acid, paeoniflorin, galloylpaeoniflorin and paeonol were the
main effective components.
PMID- 25850274
TI - [Application of near infrared spectroscopy to identify authenticity of Polygonum
multiflorum].
AB - OBJECTIVE: To establish a near-infrared qualitative analysis model to identify
the authenticity of Polygonum multiflo- rum and distinguish processed products
Polygoni Multiflori Radix. METHOD: The NIR spectra were peformed on over 30
batches of P. multiflorum and Polygoni Multiflori Radix samples and the
adulterants Cynanchum bungei, Pteroxygonum giraldii, Polygonum cillinerve to
establish the qualitative discriminant model and the conformity test model of
Polygonum multifiorum , and cluster analysis was used to analyze the samples from
different origins. RESULT: The model is able to identify correctly P. multiflorum
with its counterfeit, and distinguish between P. multiflorum and Polygoni
multiflori Radix. CONCLUSION: Near-infrared spectroscopy can be applied in the
identification of P. multiflorum, which could be used to screen Chinese herbal
medicine preliminarily.
PMID- 25850275
TI - [Protective effect of combined administration of active ingredients of Danhong on
cerebral micro-vascular endothelial cell injured by hypoxia].
AB - To study the protective effect of combined administration of active ingredients
of Danhong on cultured primary mice's brain microvascular endothelial cells
(rBMECs) injured by hypoxia. Primary mice's brain micro-vascular endothelial
cells were cultured to establish the 4 h hypoxia model. Meanwhile, active
ingredients (protocatechuic aldehyde, salvianolic acid B, hydroxysafflor yellow A
and tanshinol) of Danhong were administered in rBMECs. The non-toxic dosage was
determined by MTT. The leakage of lactate dehydrogenase(LDH), cell superoxide
dismutase (SOD) activity and MDA level were detected by the colorimetric method.
The expressions of ICAM-1, MMP-9, P53 mRNA were detected by RT-PCR method.
Changes in rBMECs cell cycle and early apoptosis were detected by flow cytometry.
Danhong's active ingredients and prescriptions 1, 2, 3, 7, 8, 9 could be combined
to significantly restrain LDH in hypoxic cells supernatant. Prescriptions 1, 2,
3, 7, 8, 9 could significantly enhance SOD activity in anoxic cells;
Prescriptions 1, 2, 3, 8, 9 could significantly decrease the MDA level;
Prescriptions 1, 2, 6, 7, 9 could significantly inhibit the early rB-MECs
apoptosis induced by hypoxia. After hypoxia, the up-regulated P53 mRNA expression
could cause retardation in G, phase and promote cell apoptosis. This proved that
the regulatory function of P53 gene lay in monitoring of calibration points in G,
phase. Prescriptions 1, 2, 5, 6, 7, 8, 9 could significantly down-regulate the
P53 mRNA expression; Prescriptions 1, 4, 7, 8, 9 could significantly down
regulate the ICAM-1 mRNA expression; Prescriptions 1, 3, 6, 9 could significantly
down-regulate the MMP-9 mRNA expression. The combined administration of Danhong's
active ingredients showed a significant protective effect on primary cultured
rBMECs injury induced by hypoxia Its mechanism may be related to the enhancement
of cellular antioxidant capacity and the inhibition of inflammatory response and
cell apoptosis. This study could provide ideas for researching prescription
compatibility, and guide the clinical medication.
PMID- 25850276
TI - [Huanglian jiedu decoction active fraction protects ipsilateral thalamus injury
in MCAO rats through regulating astrocytes].
AB - OBJECTIVE: To observe the protective effects of the Huanglian Jiedu decoction
aqueous extract and its active fraction, which consists of total alkaloids, total
flavonoids and total iridoid, on the thalamus of cerebral ischemia in rats.
METHOD: The rat model of middle cerebral artery occlusion (MCAO) was chosen. Male
SD rats were randomly divided into sham-operation group, model group, aqueous
extract group (800 mg x kg(-1)), total alkaloids group(44 mg x kg(-1)), total
flavonoids group (50 mg x kg(-1)) and the total iridoid group (80 mg x kg(-1)).
The rats were administered the appropriate drugs intragastrically once a day, for
7 days after surgery. An equivalent volume of saline was given in the sham
surgery and model groups. The HE staining was adopted to observe the pathological
changes. Determination of Glu and gamma-GABA in thalamus were detected by HPLC
with fluorescence detection. The expression of GAD65 was examined with
immunohistochemistry and double staining with uorescent-conjugated antibodies
against GFAP and Cx43 was chosen in this study. RESULT: The neurons degenerated
in MCAO rats after cerebral ischemia 7 d. The content of Glu, gamma-GABA
decreased (P < 0.05), the expression of GAD65 reduced (P < 0.05) and the
expression of GFAP and Cx43 increased (P < 0.01) in thalamus of rats compared
with sham-operation group. Huanglian Jiedu decoction aqueous extract, total
alkaloids, total flavonoids and total iridoid reduced the degeneration of
neurons. Total flavonoids could promote the expression of GAD65 (P < 0.05) and
decrease the expression of GFAP and Cx43 (P < 0.01) in thalamus compared with
model group while it could also increased the content of Glu,gamma-GA BA to
normal levels. Compared with model group, Huanglian Jiedu decoction aqueous
extract, total alkaloids and total iridoid could raise the expression of Cx43,
and Huanglian Jiedu decoction aqueous extract could also increase the expression
of GAD65 (P < 0.05). The expression of GFAP in Huanglian Jiedu decoction aqueous
extract group, total alkaloids group and total iridoid group were not different
compared with model group while the content of gamma-GABA decreased (P < 0.05)
compared with sham-operation group. CONCLUSION: The degeneration of nerve cells,
the reduction of neurotransmitter amino acids content, the aberrant activation of
astrocytes and the abnormal expression of GFAP and Cx43 will appear in thalamus
of MCAO rats after ischemia. Huanglian Jiedu decoction total flavonoids could
relieve the injury of nerve cell through inhibiting the abnormal activation of
astrocytes and regulating the expression of GFAP and GAD65.
PMID- 25850277
TI - [Method of traditional Chinese medicine formula design based on 3D-database
pharmacophore search and patent retrieval].
AB - By using the pharmacophore model of mineralocorticoid receptor antagonists as a
starting point, the experiment stud- ies the method of traditional Chinese
medicine formula design for anti-hypertensive. Pharmacophore models were
generated by 3D-QSAR pharmacophore (Hypogen) program of the DS3.5, based on the
training set composed of 33 mineralocorticoid receptor antagonists. The best
pharmacophore model consisted of two Hydrogen-bond acceptors, three Hydrophobic
and four excluded volumes. Its correlation coefficient of training set and test
set, N, and CAI value were 0.9534, 0.6748, 2.878, and 1.119. According to the
database screening, 1700 active compounds from 86 source plant were obtained.
Because of lacking of available anti-hypertensive medi cation strategy in
traditional theory, this article takes advantage of patent retrieval in world
traditional medicine patent database, in order to design drug formula. Finally,
two formulae was obtained for antihypertensive.
PMID- 25850278
TI - [Mechanism study on preventive and curative effects of buyang huanwu decoction in
Qi deficiency and blood stasis diseases based on network analysis].
AB - In this study, researchers adopted the network analysis method to study Buyang
Huanwu decoction at three levels, namely chemical ingredients, targets and
diseases, and discovered the potential effect of Buyang Huanwu decoction in
cancer treatment. Besides, they analyzed the "target-target" network of Buyang
Huanwu decoction based on diseases, calculated four network indexes, namely node
centrality, closeness centrality, betweenness centrality and eigenvector
centrality for a comprehensive evaluation on the importance and significance of
each target in the network. Afterwards, key targets of Buyang Huanwu decoction
were excavated to obtain two important targets--COX-2 and PPAR-gamma, which may
be important targets involved in the qi deficiency and blood stasis diseases.
Meanwhile, the two targets were the basis to build the core network of "chemical
component-target-disease" of Buyang Huanwu decoction, which provided reference
for further studies on the effect of Buyang Huanwu decoction in treating qi
deficiency and blood stasis diseases. According to the study, the network
analysis method was helpful to excavate potential targets Buyang Huanwu decoction
in treating qi deficiency and blood stasis diseases, and could provide
methodological reference for revealing the mechanism of Buyang Huanwu decoction
at multiple levels, with a guiding significance for interpreting mechanisms of
traditional Chinese medicinal formulae and developing new drugs.
PMID- 25850279
TI - [Effects of methyl cantharidimide tablets on urinary protein and enzymes in
Beagle dogs].
AB - OBJECTIVE: To investigate the nephrotoxic effects of methyl cantharidimide
tablets on urinary protein and enzymes in Beagle dogs. METHOD: Beagle dogs were
randomly divided into negative control group(blank tablet), methyl cantharidimide
tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral
adminiStration, once a day. The drug and control group were collected and
determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea
nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well
as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of
the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1),
neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D
glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1
microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG
were tested on 15 and 30 days of the administration. RESULT: Compared with the
control group, urine protein and white blood cells was significantly increased in
each dose group. On 15 days of the administration, mAlb were higher in each dose
group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose
group, while the middle and low dose group had no significant difference, as well
as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1,
clusterin, NAG, AAP were increased in each dose group, appearing dose-effect
relationship, beta2-MG and NGAL levels were significantly increased in high-dose
group. Contents above indicators were increased with significant dose and time
relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM
1, clusterin, NAG and AAP indicators that can sensitively respond the changes of
proteins and enzymes in urine. CONCLUSION: Methyl cantharidimide tablets has a
renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the
early nephrotoxic biomarkers of methyl cantharidimide tablets.
PMID- 25850280
TI - [Protective effect of astragaloside IV on oxidative damages of chang liver cell
induced by ethanol and H2O2].
AB - OBJECTIVE: To study the protective effect of astragaloside IV on oxidative
damages of Chang Liver cells induced by ethanol and H2O2. METHOD: The alcoholic
and nonalcoholic oxidative damage models were established on Chang Liver cells
with ethanol and H2O2, respectively. The cells viabilities were detected by MTT
assay, transaminase activity and antioxidant ability were detected by micro plate
and colorimetric method, reactive oxide species (ROS) was detected by DCFH-DA
fluorescent probe and cell cycle was detected by flow cytometry. DNA ladder
method was used to detect apoptosis. RESULT: Both kinds of oxidative damage could
decrease the viability and antioxidant enzyme activity of Chang Liver cells, and
increase the transaminase activity and MDA content of extracellular fluid. The
protective effects of astragaloside IV against those two kinds of oxidative
damages were significant or extremely significant. Meanwhile, ethanol could
decline the level of ROS significantly in the damaged cells, while H2O2 could
increase it significantly. And the effect of astragaloside IV was to make ROS
return to the normal level. Retardation of cell cycle progression of Chang Liver
cells in G0/G1 induced by ethanol or H2O2 was relieved, and apoptosis was also
inhibited. CONCLUSION: Astragaloside IV had protective effect on oxidative
damages of Chang Liver cells induced by ethanol and H2O2.
PMID- 25850281
TI - [Effects of component formula of Salviae Miltiorrhizae Radix et Rhizoma and
Ginseng Radix et Rhizoma on cell proliferation, apoptosis and skeleton in lung
cancer A549 cells].
AB - This study aims to optimize the most effective component formula of Salviae
Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549
using the orthogonal design method, and to investigate its effects of the
component formula on cell proliferation, apoptosis and cytoskeleton in lung
cancer A549 cells. The orthogonal design method was introduced to optimize the
most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and
Ginseng Radix et Rhizoma on lung cancer A549 cells. CCK-8 assay and Real-time
cell analysis were adapted to analyze the effect of component formula of Salviae
Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on A549 cells
viability at different time and dose. Cell apoptosis was measured by Annexin V-
FITC/PI double staining and flow cytometry. Cell skeleton protein F-actin was
detected by high content screening (HCS). The optimizing component formula of
Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma for total
salvianolic acid, total saponins of panax ginseng and ginseng polysaccharide
doses were 5, 10, 5 mg L(-1). CCK-8 assay and real-time cell analysis
demonstrated that the component formula of Salviae Miltiorrhizae Radix et Rhizoma
and Ginseng Radix et Rhizoma treatment could significantly decrease the A549 cell
viability in both dose- and time-dependent manner compared with control group (P
< 0.01). Moreover, the increase of cell apoptosis was detected by Annexin V
FITC/PI double staining and flow cytometry when cells treated with the component
formula, which indicating that the component formula of Salviae Miltiorrhizae
Radix et Rhizoma and Ginseng Radix et Rhizoma could induce A549 cell apoptosis in
a time-dependent manner compared with control group (P < 0.01). Furthermore,
compared with control group, a significant decrease in A549 cell skeleton area
was found in the component formula-exposed cells in the dose-dependent manner (P
< 0.01). In summary, the component formula of Salviae Miltiorrhizae Radix et
Rhizoma and Ginseng Radix et Rhizoma inhibits A549 cell proliferation by inducing
cell apoptosis and decreasing cell microfilament formation. All of these results
will be helpful to reveal antitumor mechanism of the component formula of Salviae
Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma, which provides a
basis for the exploration of antitumor mechanism of the component formula on lung
cancer.
PMID- 25850282
TI - [Research of anti-aging mechanism of ginsenoside Rg1 on brain].
AB - Neurodegenerative disease is common and frequently occurs in elderly patients.
Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of
brain, but the mechanism on the brain during the treatment remains elucidated. To
study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain,
forty male SD rats were randomly divided into normal group, Rg1 normal group,
brain aging model group and Rg1 brain aging model group, each group with 10 rats
(brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)),
qd for 42 consecutive days; Rg1 brain aging model group: while copying the same
test as that of brain aging model group, begin intraperitoneal injection of
ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group:
subcutaneous injection of the same amount of saline; begin intraperitoneal
injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal:
injected with an equal volume of saline within the same time. Perform the related
experiment on the second day after finishing copying the model or the completion
of the first two days of drug injections). Learning and memory abilities were
measured by Morris water maze. The number of senescent cells was detected by SA
beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in
hippocampus were detected by ELISA. The activities of SOD, contents of GSH in
hippo- campus were quantified by chromatometry. The change of telomerase
activities and telomerase length were performed by TRAP-PCR and southern blotting
assay, respectively. It is pointed that, in brain aging model group, the spatial
learning and memory capacities were weaken, SA-beta-Gal positive granules
increased in section of brain tissue, the activity of antioxidant enzyme SOD and
the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6
increased in hippocampus, while the length of telomere and the activity of
telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their
spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in
section of brain tissue decreased, the activity of antioxidant enzyme SOD and the
contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in
hippocampus decreased, the length contraction of telomere suppressed while the
change of telomerase activity increased in hippocampus. Compared with that of
normal group, the spatial learning and memory capacities were enhanced in Rg1
normal group, SA-beta-Gal positive granules in section of brain tissue decreased
in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1
normal group. The results indicated that improvement of antioxidant ability,
regulating the level of proinflammatory cytokines and regulation of telomerase
system may be the underlying anti-aging mechanism of Ginsenoside Rg1.
PMID- 25850283
TI - [Ginsenoside Rb1 upregulates expressions of GLUTs to promote glucose consumption
in adiopcytes].
AB - Previous studies have shown that ginsenoside Rb1 (Rb1), one of active components
in ginseng, can activate insulin signaling pathway and promote translocation of
glucose transporters (GLUTs) to increase glucose uptake in adipocytes. However,
the effect of Rb1 on the expressions of GLUTs remains unknown. In this study, the
effects of Rb1 on GLUT1 and GLUT4 were observed in 3T3-L1 adipocytes and
epididymal adipose tissue of db/db obese diabetic mice. Male db/db mice were
treated with Rb1 by intraperitoneal injection at the dosage of 20 mg x kg(-1) for
14 d. Rb1 reduced HOMA-IR significantly (P < 0.05, n = 5), and FBG and FINS sowed
declining trend after treatment with Rb1. Rb1 recovered the expressions of GLUT1
and GLUT4 and phosphorylation of AKT in adipose tissue of db/db mice. In vitro,
glucose consumption in 3T3-L1 adipocytes treated with 10 micromol x L(-1) Rb1 for
24 h was elevated (P < 0.05, n=3), and mRNA of GLUT1 and GLUT4 were up-regulated
(P < 0.05, n=3) and proteins of GLUT1 and GLUT4 were also increased. AKT was
activated in adipocytes treated with Rb1 for 3 h. It can be concluded that
ginsenoside Rb1 can up-regulate the expression of GLUTs in adipose tissue, in
addition to activate insulin signalling pathway, which may partially account for
its insulin sensitizing activity and regulating effect of glucose metabolism.
PMID- 25850284
TI - [Effects of xuefu zhuyu decoction on antioxidant and drug-metabolizing enzymes in
liver of rats].
AB - Xuefu Zhuyu decoction (XFZYD) is a famous traditional Chinese medicine (TCM)
formula, is widely used in the treatment of cardiovascular and cerebrovascular
diseases in China over one hundred years. But its effect on antioxidant and drug
metabolizing enzymes are unknown. This study was to observe the effects of Xuefu
Zhuyu decoction (XFZYD) on the activities of antioxidant and drug metabolism
enzymes (DMEs) in liver of rats. Male SD rats, treated with XFZYD at the dosage
of 3.51, 7.02 and 14.04 g x kg(-1) per day for 15 days, serum were collected,
tissue fluid, cytosols and microsomes isolated from liver tissues were prepared
by centrifugation according to the standard procedure, the activities of
antioxidant enzymes and drug-Metabolizing Enzymes were determined by UV-V is
spectrophotometer. In serum, the activities of AST was not significantly affected
by the treatment with XFZYD, at the high- est dose, the levels of ALT, Cr and BUN
were significantly decreased (P < 0.05). GPX were significantly increased at the
dose of 7.02, 14.04 g x kg(-1) (P < 0.05), CAT were significantly increased at
the highest dose (P < 0.05). T-SOD was not significantly af- fected by this
treatment. In the liver tissue, GPX was significantly increased at the dose of
3.51, 7.02 g x kg(-1) (P < 0.05), GST, CAT and T-SOD were not significantly
affected following this treatment. In cytosols, GST was significantly increased
at the dose of 3.51 g x kg(-1) (P < 0.05), T-SOD was remarkable induced at the
dose of 3.51 and 7.02 g x kg(-1) (P < 0.05). In microsomes, XFZYD had no
significant effect on Cytochromeb5, NADPH-Cytochrome P450 reductase, CYP3A,
CYP2E1 and UGT, XFZYD significantly in- duced GST at the dose of 3.51 and 7.02 g
x kg(-1) (P < 0.05), and the level of GSH were significantly increased by XFZYD
at the dose of 3.51, 7.02 and 14.04 g kg(-1) (P < 0.05). These findings suggest
XFZYD can induce the activities of GPX, CAT, SOD, GST and increase GSH level in
liver of rats, which indicate XFZYD may have detoxification and antioxidant
functions.
PMID- 25850285
TI - [Effect of oligosaccharide esters and polygalaxanthone Ill from Polygala
tenuifolia willd towards cytochrome P450].
AB - Five compounds (tenuifoliside C, tenuifoliside D, telephiose A, telephiose C and
polygalaxanthone III) from polygala tenuifolia wild were incubated together with
CYP probe substrate in human liver microsomes to investigate the inhibitory
effect towards CYP450 enzyme. Phenacetin (CYP1A2), coumarin (CYP2A6), paclitaxel
(CYP2C8), diclofenac (CYP2C9), S-mepheriytoin (CYP2C19), dextromethorphan
(CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A) were selected as the isoforfn
specific substrate. And the formation of paracetamol, 7-hydroxycoumarin, 6alpha
hydroxy paclitaxel, 4'-hydroxydiclofenac, dextrorphan, 6-hydroxychlorzoxazone, 1'
hydroxymidazolam, 4'-hydroxymephenytoin were detected respectively to measure the
effect towards CYP450 by high-pressure liquid chromatography (HPLC). The result
shows that five compounds from polygala tenuifolia willd significantly inhibit
chlorzoxazone 6-hydroxylation catalyzed by CYP2E1, while showed no effect towards
CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A. And IC50 value was 38.73,
54.14, 61.77, 62.22, 50.56 micromol x L(-1), respectively.
PMID- 25850286
TI - [Analysis on medication rules of state medical master yan zhenghua's
prescriptions that including Polygoni Multiflori Caulis based on data mining].
AB - The prescriptions including Polygoni Multiflori Caulis that built by Pro. Yan
were collected to build a database based on traditional Chinese medicine (TCM)
inheritance assist system. The method of association rules with apriori algorithm
was used to achieve frequency of single medicine, frequency of drug combinations,
association rules between drugs and core drug combinations. The datamining
results indicated that in the prescriptions that including Polygoni Multiflori
Caulis, the highest frequency used drugs were parched Ziziphi Spinosae Semen,
Ostreae Concha, Ossis Mastodi Fossilia, Salviae Miltiorrhizae Radix Et Rhizoma,
Paeoniae Rubra Radix, and so on. The most frequent drug combinations were
"Polygoni Multiflori Caulis-parched Ziziphi Spinosae Semen", "Ostreae Concha
Polygoni Multiflori Caulis", and "Polygoni Multiflori Caulis-Ossis Mastodi
Fossilia". The drug association rules of confidence coefficient 1 were "Ostreae
Concha-->Polygoni Multiflori Caulis", "Poria-->Polygoni Multiflori Caulis",
"parched Ziziphi Spinosae Semen-->Polygoni Multiflori Caulis", and "Paeoniae Alba
Radix-->Polygoni Multiflori Caulis". The core drug combinations in the treatment
of insomnia were Ossis Mastodi Fossilia, Polygoni Multiflori Caulis, Salviae
Miltiorrhizae Radix et Rhizoma, Ostreae Concha, Polygalae Radix, Margaritifera
Concha, Poria, and parched Ziziphi Spinosae Semen. And the core drug combinations
in the treatment of obstruction of Qi in chest were Salviae Miltiorrhizae Radix
Et Rhizoma, Polygoni Multiflori Caulis, parched Ziziphi Spinosae Semen,
Trichosanthis Fructus, Allii Macrostemonis Bulbus, and Paeoniae Rubra Radix.
PMID- 25850287
TI - [Analysis on formula raw materials application of health food containing
Gardeniae fructus].
AB - In this article we built formula database of health food containing Gardeniae
Fructus with Traditional Chinese Medicine Inheritance Support System (V2.0). And
on this basis, use data mining method such as association rules of the software,
to analyze commonly used formula raw materials or materials combination of
formula containing Gardeniae Fructus and raw material application having assisted
function formula to protect chemical liver injury. The result shows that of the
71 health food formulas containing Gardeniae Fructus, most used materials are
Gardeniae Fructus, Lycii Fructus, Angelica Sinensis Radix, Poria and so on.
Commonly used materials combination mostly are Gardeniae Fructus and Lycii
Fructus, Gardeniae Fructus and Angelica Sinensis Radix, Gardeniae Fructus and
Poria, Gardeniae Fructus and Paeonia. There are nearly 18 healthcare functions of
the health food containing Gardeniae Fructus, and most of these are assisted
functions to protect chemical liver injury, and then immune modulating function.
Of 23 formulas containing Gardeniae Fructus having assisted function formula to
protect chemical liver injury, Gardeniae Fructus usually combined with
traditional Chinese medicine which nourishs blood and liver such as Pueraria,
Lycii Fructus, Hawthorn, Paeonia and Turnjujube. Analyzing formula raw materials
application of health food containing Gardeniae Fructus contributes a lot to the
further development and utilization.
PMID- 25850288
TI - [Development of Chinese herbal pieces and analysis of problems of total quality
management].
AB - Chinese herbal pieces are a key factor to protecting the quality of the clinical
efficacy of traditional Chinese medicine (TCM), and it is one of the basic
elements of ensuring the quality of TCM and people's usage safety. However,
Chinese herbal pieces has massive problem such as adulteration and counterfeit,
dyeing and weighting, pesticide residues, heavy metals in excess of the
standards, and all the issues are repeated excessive in the clinic treatment.
These issues impacted sound development of production, management and use of TCM,
but also brings common people hidden trouble for the clinical safety of
medication. Protect and improve the quality of the Chinese herbal pieces demand
that continue improve quality system, in-depth scientific research, and
strengthen self-discipline and other factors. So it is fundamentally to ensure
good quality of Chinese herbal pieces with the color, taste and shape by
systematic supervision to it from the source, production, management and
research, with strengthened implementation and en- forcement of the "3G".
PMID- 25850289
TI - [The cellular mechanisms and regulation of metastasis formation].
AB - Recent data obtained at the junction of biochem: istry, molecular and cell
biology and experimental oncology, showed that the formation of secondary foci of
tumor growth during cancer progression--metastasis formation--is a highly
determinate and regulated process. This process includes on the one hand the
appearance of metastatic population of cells with special characteristics that
allow their dissemination and seeding in distant organs and on the other.hand the
formation of specific attractive micro environment in target organs. These cells
show the ability to switch their motility to the most effective mode depending on
the properties of the surrounding tissues (plasticity), appearance of specific
receptors on the cell surface, which enhance their directed migration to target
organs and acquisition of some characteristics of stem cells, allowing them to
survive and reproduce in alien microenvironment. These alterations are strongly
coordinated with development of a specific nichein the target organ which
stimulates initiation and growth of a future metastasis, so-called premetastatic
niche. In this review we analyzed recent data concerning mechanisms which
regulate the emergence of metastatic population of cells, development of
premetastatic niches and coordination of these processes:.
PMID- 25850290
TI - [Cellular targets of antitumor ribonucleases].
AB - Some ribonucleases (RNases) produce selective toxic effect on the cancer cells.
The mechanism of this antitumor activity remains largely unclear. The subject of
this review is the RNases interaction with cellular components, resulting in the
induction of apoptosis of tumor cells. Cell surface structures, which are
potential acceptors of the exogenous RNase are discussed: acidic lipids and
glycoproteins, heparansulfate-containing proteoglycans, actin, and RNA-associated
proteins. Cell membranes of normal and malignant cells differ according to the
composition of these components, which largely determines the selectivity of
RNases for the latter. Different types of RNA are examined as intracellular
targets of the RNases activity, evidence is presented demonstrating the
possibility of exogenous RNases intervening in the process of RNA interference.
The role of potassium channels, NF-kappaB-dependent.signaling pathway and various
caspases in apoptosis induced by exogenous RNases is discussed. Evidence is also
presented showing that the sensitivity of cells to exogenous RNases is linked to
the expression of certain oncogenes, namely RAS, KIT, AML1-ETO. It is suggested
that discovering the details of the mechanisms of RNases cytotoxic effect in
malignant cells susceptible to their activity, will in the future serve as a
foundation to developing new tools of targeted anticancer therapy.
PMID- 25850291
TI - [Multifunctional protein complex NAC (nascent polypeptide associated complex].
AB - The functions of the evolutionary conservative complex NAC (Nascent polypepetide
Associated Complex) and its subunits are discussed. The heterodimeric NAC protein
contains alpha- and beta-subunits and is found to be reversibly bounded to the
ribosome in all eukaryotes, from yeast to humans. NAC contacts the nascent
polypeptide and protects it from proteolysis. NAC participates in polypeptide
chain folding and modulates protein secretion and transmembrane protein
formation. Mutations and deletions of genes, encoding NAC subunits are lethal in
early development of multicellular eukaryotes. NAC is involved in the ribosome
biogenesis. The beta-subunit interacts with caspase-3 and may be involved in the
regulation of the apoptotic pathway. The variants of NAC proteins can be
considered as chaperone complexes, involved in the response of the cell and the
organism to stress factors, as well as regulators of apoptosis. The genes
encoding beta-subunits are rapidly evolved, their duplications cause the
formation of tissue specific beta-subunit variants with a different number of
putative caspase cleavage sites. The homodimer of alpha-subunits is shown to be
the RNA/DNA binding protein and acts as a transcriptional cofactor. The diversity
in the functioning of NAC is a prime example of a protein that performs a variety
of biological functions (moonlighting protein).
PMID- 25850292
TI - [MicroRNA and cancer].
AB - Review is devoted to analysis of the role of microRNA in progression of human
tumors. The following aspects of this problem are discussed: general
characteristics of microRNA, expression pattern of these RNAs in human tumors and
specificity of this expression, putative role of microRNAs as oncogenes and tumor
suppressors for tumor growth, participation of microRNAs in induction of
transformed phenotypes of tumor cells, possible role of microRNAs for early
diagnosis of the disease and prognosis.
PMID- 25850293
TI - [Genotyping of BRCA1, BRCA2 and CHEK2 germline mutations in Russian breast cancer
patients using diagnostic biochips].
AB - Germline mutations of BRCA1/2 genes cause the predisposition of their carriers to
breast or/and ovary cancers (BC or/and OC) during the lifetime. Identification of
these mutations is a basis of molecular diagnosis for BC susceptibility. Rapid
genotyping technique using microarrays for identification of BRCA1 185delAG,
300T>G, 4153delA, 5382insC mutations and 4158 A>G sequence variant; BRCA2 695insT
and 6174delT mutations; 1100delC mutation in CHEK2 gene was applied for 412
randomly collected breast cancer samples from the central region of European area
of Russia. In 25 (6.0%) patients (6.0%) BC was associated with other tumours: OC,
cervical cancer, colorectal cancer etc. BRCA1/2 and CHEK2 mutations were found in
33 (8.0%) BC patients. The most frequent mutation was BRCA1 5382insC, occurred in
16 (3.9%) BC patients, and CHEK2 1100delC, revealed in 7 (1.7%) BC patients. An
application of diagnostic BC-microarray for genetic testing of BRCA1/2 and CHEK2
founder mutations has been discussed.
PMID- 25850294
TI - [Analysis of genetic determinants of multidrug and extensively drug-resistant
Mycobacterium tuberculosis using oligonucleotide microchip].
AB - Steadily growing resistance of the tuberculosis causative agent towards a broad
spectrum of anti-tuberculosis drugs calls for rapid and reliable methods for
identifying the genetic determinants responsible for this resistance. In this
study, we present a biochip-based method for simultaneous identification of
mutations within rpoB gene associated with rifampin resistance, mutations in
katG, inhA, ahpC genes responsible for isoniazid resistance, mutations within the
regions of gyrA and gyrB genes leading to fluoroquinolones resistance, and
mutations in the rrs gene and the eis promoter region associated with the
resistance to kanamycin, capreomycin and amikacin. The oligonucleotide microchip,
as the core element of this assay, provides simultaneous identification of 99
mutations in the format "one sample--one PCR--one microchip", and it makes it
possible to complete analysis of multi-drug-resistant and extensively drug
resistant tuberculosis within a single day. The tests on 63 Mycobacterium
tuberculosis clinical isolates with different resistance profiles using the
developed approach allows us to reveal the spectrum of drug-resistance associated
mutations, and to estimate the significance of the inclusion of extra genetic
loci in the determination of M. tuberculosis drug resistance.
PMID- 25850295
TI - [Association of polymorphisms in toll-like receptor genes with atopic dermatitis
in the Republic of Bashkortostan].
AB - Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease
developing as a result of the interaction between genetic predisposition and
environmental factors. Considerable role in allergic diseases development is
played by polymorphisms of genes of pattern-recognition receptors (PRR) which are
capable of recognizing conservative standard molecular structures (patterns)
unique for large pathogen groups. In this study polymorphic variants of PRR genes
-Toll-like receptors (TLR1, TLR2, TLR4, TLR5, TLR6, TLR9, TLR10), NOD-like
receptors (NOD1, NOD2), lipopolysaccharide receptor CD14 gene, and C11orf30 and
LRRC32 genes, located in 11q13.5 region, have been investigated in AD patients
and control subjects from the Republic of Bashkortostan. An association of TLR1
(rs5743571 and rs5743604), TLR6 (rs5743794) and TLR10 (rs11466617) with AD was
found. Our results confirm an important role of the innate immune system in the
pathogenesis of AD and the significance of polymorphisms within the Toll-like
receptor 2 subfamily genes in AD development.
PMID- 25850296
TI - [Effect of tripeptide Pro-Gly-Pro on rat brain transcriptome in focal ischemia].
AB - Biologically active regulatory peptide, tripeptide Pro-Gly-Pro (PGP) was used as
C-terminal fragment for peptide drugs Semax and Selank. In recent years the
independent effects of PGP were observed. The question was raised, whether PGP
contributes to the effects ofpeptide drugs containing PGP as a fragment. The
genome-wide analysis was performed to investigate the influence of PGP on the
transcriptome of ischemic rat brain cortex tissues. The gene expression
alterations caused by the action of the tripeptide PGP were compared with the
gene expression of the control group "ischemia" at 3 and 24 h after permanent
occlusion of left middle cerebral artery. The altered expression was detected for
29 genes at 3 h and 57--at 24 h. The proteins encoded by these genes have variety
of functions: cytokines, transport proteins, transcription factors, transmembrane
receptors, etc. Biological processes, which are related to the genes with altered
expression, were distinguished. The influence of PGP on the diversity of
biological processes in different systems of the organism is demonstrated for the
first time. The process "Immune response" was the most statistically notable at
24 h after occlusion. The expression of the immune system genes was predominately
down regulated.
PMID- 25850297
TI - [Functional characterization of two novel splicing mutations in glucokinase gene
in monogenic diabetes MODY2].
AB - Two novel mutations in glucokinase (GCK) gene-G to C substitution at -1 position
of intron 7 acceptor splice site (c. 864-1G>C) and synonymous substitution c.
666C>G (GTC>GTG, p.V222V) in exon 6--were identified in patients with monogenic
diabetes MODY2 (Maturity Onset Diabetes of Young). GCK minigenes with these
mutations were constructed. Analysis of splicing products upon transfection of
minigenes into human embryonic cell line HEK293 has shown that each of these
nucleotide substitutions impair normal splicing. Mutation c.864-1G>C blocks the
usage of normal acceptor site which activates cryptic acceptor splice sites
within intron 7 and generates aberrant RNAs containing the portions ofintron 7.
Synonymous substitution c.666C>G creates novel donor splice site in exon 6 that
leads to formation of defective GCK mRNA with deletion of 16 nucleotides of exon
6. Analysis of in vitro splicing of minigenes confirms the inactivating action of
novel mutations on glucokinase expression.
PMID- 25850298
TI - [The 3'-UTR polymorphism of dopamine transporter gene in hadza and datoga males].
AB - The study of VNTR-polymorphism and the molecular struc ture of 3'-UTR of the
dopamine transporter gene (DAT1/SLC6A3) was performed in hadza and datoga males.
It was shown that hadza and datoga differed in allele and genotype frequencies.
Allele with 9 repeats in 3'-UTR is more common in hadza as well as homozygous
genotype DAT19/9. Allele with 10 repeats is more common in datoga as well as
homozygous genotype DAT1 10/10. The molecular structure of the DAT alleles with
3, 8 and 12 repeats was determined for the first time. In addition it was found
that DAT1 allele with 11 repeats in datoga significantly differed from previously
described ones in other populations in repeats type and arrangement. We suggest
that variations of the repeats num ber and type in the 3'-UTR of allelic variants
may affect the dopamine transporter gene function.
PMID- 25850299
TI - [Sub-celluiar localization of PELPK1 in Arabidopsis thaliana as determined by
translational fusion with green fluorescent protein reporter].
AB - PELPK1, a novel Arabidopsis thaliana gene was earlier annotated to encode a
protein of sub-family, PELPK under hydroxyproline-rich glycoprotein (HRGP) super
family of proteins. Previous bioinformatics and computational analyses predicted
PELPK1 to contain an amino-terminal signal peptide destined towards the secretory
pathway. In the present study, transgenic plants were developed harboring a
translational fusion construct comprising of PELPK1 coding sequence (PELPK1-CDS)
and green fluorescent protein (GFP) reporter to determine the localization of
PELPK1 in Arabidopsis plants. By employing the techniques of confocal laser
scanning microscopy, immunolabeling of GFP with quantum dot (Q-dot), and
transmission electron microscopy (TEM), it is shown that the translational fusion
product is predominantly deposited to the cell wall. These results are in
agreement with the earlier bioinformatics prediction that the PELPK1 is
transported via the secretory pathway.
PMID- 25850300
TI - [Kinetics of heat shock response upon disfunction of general transcription factor
(HSF)].
AB - The heat shock transcription factor (HSF) is a universal activator of hsp gene
expression in eukaryotes. A temperature sensitive Drosophila melanogaster strain
(hsf4) with a mutation in the hsfgene was originally described as a strain
lacking the transcription of hsp genes in response to heat shock. Our results
demonstrated that physiological function of HSF4 is not fully abrogated after
heat exposure and is able to recover even after severe heat stress, causing the
induction of hsp gene expression. We have studied the kinetics of accumulation
and degradation of hsp gene products at transcriptional and translational levels
and shown that induction of hsp genes, particularly hsp68, in mutant strain is
weaker than that in the wild type. Thus, despite the fact that the HSF4 causes a
delayed ac- tivation of hsp, response to heat shock in hsf4 strain remains
defective.
PMID- 25850301
TI - [Modification of [PSI+] prion properties by the combination of amino acid changes
within Sup35 protein N-domain].
AB - [PSI+] prion is an amyloid isoform of a release factor Sup35p (eRF3). The
structure of these protein aggregates remains unclear despite a long term history
of prion amyloids investigations. The N-terminal domain of Sup35p (which is
responsible for a propagation of prion) shapes superpleated beta-structure,
according to modern concepts. Recently we constructed five double mutations
within SUP35 sequence encoding the N-terminal prion-forming domain and
investigated properties of mutant proteins. Mutations sup35-M1 (YQ46-47KK) and
sup35-M2 (QQ61-62KK) lead to [PSI+] prion loss, while other mutant alleles (sup35
M3 QQ70-71KK; sup35-M4 QQ80-81KK; sup35-M5 QQ89-90KK) maintained prion. For the
detail analysis of effects of mutant alleles on Sup35p aggregation we
characterized propagation and properties of [PSI] prion in yeast strains bearing
different mutant allele combinations. The data obtained have refined a supposed
organization of beta-sheets forming by different regions of Sup35p prion-forming
domain within amyloid. Also we obtained evidences that mutant sup35-M2 and sup35
M4 alleles change structure of prion aggregates. The prion destabilization by
these mutations possibly is connected with decrease of heteroaggregate
fragmentation by chaperones.
PMID- 25850302
TI - [In silico structural characterization and molecular docking studies of first
glucuronoxylan-xylanohydrolase (Xyn30a) from family-30 glycosyl hydrolase (GH30)
from Clostridium thermocellum].
AB - CtXynGH30 is a carbohydrate active modular enzyme and component of cellulosome of
Clostridium thermocellum. The full length CtXynGH30 contains an N-terminal
catalytic module named as Xyn30A and a family 6 carbohydrate binding module
(CBM6) at C-terminuis. Xyn30A was modeled by computer program Modeller9v8 taking
crystal structure of XynC from B. subtilis as a template to generate the
molecular model. Model refinement was done using energy minimization by
implementing steepest descent algorithm with GROMOS96 43al force field. Quality
assessment by Ramachandran plot showed that 91% amino acids lie in most
favourable region and 9% in additional allowed region. Structural analysis
depicted that Xyn30A has a (beta/alpha)8 barrel fold. Ad- ditionally, it had a
beta-strand rich structure called 'side beta-structure' attached with main
catalytic core. Structural superimposition reflected that Glu136 act as a
catalytic acid/base while Glu225 act as a catalytic nucleophile. Multiple
sequence alignment showed that these catalytic residues are conserved within the
family. The docking results showed that these residues display polar interaction
with linear and substituted xylo-oligosaccharides. The binding interaction of
ligands depicted that aromatic amino acids Trp81, Tyr139, Trp143, Phe172, His198,
Tyr200, Tyr227, Trp264 and Tyr265 create binding site pocket around the active
site. We report overall structural feature, conserved active site residues and
enzymeligand docking of first glucuronoxylan-xylanohydrolase (Xyn30A) of family
30 glycosyl hydrolase (GH30) from Clostridium thermocellum.
PMID- 25850303
TI - [Combining protein-protein interactions information with support vector machine
to identify chronic obstructive pulmonary disease related genes].
AB - Chronic obstructive pulmonary disease (COPD) is a complex human disease with a
higher mortality. So far, the studies to COPD have not been well characterized
despite the well-documented role of cigarette smoking in the genesis of COPD. In
recent years, microarray analyses have help to identify some potential disease
related genes. However, the low reproducibility of many published gene signatures
has been criticized. It therefore suggested that incorporation of network or
pathway information into prognostic biomarker discovery might improve the
prediction performance. In this analysis, we combined protein-protein
interactions (PPI) information with support vector machine (SVM) method to
identify potential COPD-related genes that would allow one to distinguish
accurately severe emphysema from non-/mildly emphysematous lung tissue. We
identified 8 COPD-related feature genes. When compared with another SVM method
which did not use the prior PPI information, the prediction accuracy was
significantly enhanced (AUC is increased from 0.513 to 0.909). On the base of
results obtained one can suppose that incorporating network of prior knowledge
into gene selection methods significantly improves classification accuracy.
Consequently, the gene expression profiles from human emphysematous lung tissue
may provide insight into pathogenesis, and a good classify prediction algorithm
based on prior biology knowledge can further strengthen this performance.
PMID- 25850304
TI - [Universal modular system for in vitro screening of potential inhibitors of HIV-1
replication].
AB - Here we describe a system based on recombinant lentiviral vectors for the safe
screening of potential anti-HIV drugs. The system allows to evaluate the
sensitivity of HIVl-1 reverse transcriptase and integrase (wild-type as well as
mutant forms of these enzymes detected in drug-resistant virus isolates) towards
different drugs and substances, but also to screen inhibitors of other stages of
HIV-1 life cycle.
PMID- 25850305
TI - [The intracellular localization of the regulatory proteins of the densovirus of
German cockroach, Blattella germanica].
AB - The intracellular localization of the regulatory proteins encoded by the genome
of the densovirus of German cockroach was analyzed using western-blotting of
nuclear and cytoplasmic extracts of the densovirus-infected passaging cells
tissue culture BGE-2. Two of the three regulatory proteins, NS1 and NS3, were
shown to possess mainly nuclear localization, while NS2 protein was distributed
between the nucleus and cytoplasm. Data obtained provide new information
necessary for prediction of the functions of densovirus regulatory proteins.
Intracellular localization of NS3 protein was described for the densoviruses for
the first time.
PMID- 25850306
TI - [Spread of tropical malaria in the Republic of Tajikistan (1994-2008)].
AB - Tropical malaria occurred in the Republic of Tajikistan in 1994 after 40-year
absence and spread in 28 regions of Tajikistan and in 3 cities (Dushanbe, Kulyab,
and Kurgan-Tyube), peaking in 2000 (831 cases). A total of 3585 cases of tropical
malaria were notified in 602 foci during a 15-year period. Migrants imported the
pathogenic agent by the route of Pakistan-Afghanistan-Tajikistan during armed
conflicts and in trading activities continually.The emergence of Asian Plasmodium
falciparum phenotypes was accompanied by the clinical complications of the
disease: the high percentage of moderate and severe forms of the disease was
observed in preschool children in the absence of fatal outcomes. The rising
incidence of malaria was associated with not only with the intensive import of
the infection and the flight of infected malaria mosquitoes, but also with the
active examination of the population during homestead rounds and with the timely
laboratory diagnosis of malaria pathogens. The long-term goal antimalarial
measures in the Republic of Tajikistan in 2009 resulted in the pause in the local
transmission of tropical malaria, which meant its elimination in the country.
PMID- 25850307
TI - [Achievement of the elimination of tropical malaria in The Republic of
Tajikistan].
AB - To achieve the elimination of tropical malaria, Tajikistan divided its territory
into districts in terms of the malariogenic potential (receptivity +
vulnerability) and identified priority regions to be exposed, determined the
population's fever background and the required personnel, equipment, and reagents
for parasitological examinations, and compiled an inventory of malaria foci. The
investigators tested a new (artesunate + sulfadoxine-pyrimethamine) treatment
regimen in patients with tropical malaria and in parasite carriers and
established active detection of malaria cases through homestead rounds and
population examinations. The packages of antimalarial measures were improved, by
annually evaluating their efficiency in accordance with the monitoring and
estimation indicators.
PMID- 25850308
TI - [Behavioral features of the imago of malaria mosquitoes (Diptera, Culicidae,
Anopheles) in uzbekistan].
AB - Morphological, cytogenetic, and molecular genetic analyses made in the Fergana,
Chirchik-Akhangaran, Mirzachul, and Zarafshan physicogeographical districts of
Uzbekistan revealed the closely related species An. artemievi malaria mosquito
from the An. maculipennis complex. In the human settlements and natural biotopes
under their canopy of 7 physicogeographical districts of Uzbekistan, there were 6
Anopheles mosquito species (An. artemievi, An. claviger, An. hyrcanus,
An.martinius, An. pulcherrimus, and An. superpictus); An. superpictus is a
dominant species in the human settlements and An. artemievi in subdominant.
An.pulcherrimus was dominant and An. superpictus was subdominant under natural
canopy conditions. The latter is of widespread occurrence in the mountain and
piedmont areas of Uzbekistan. It is encountered in all the physicogeographical
districts. An. artemievi is distributed in the river valleys in the Fergana,
Chirchik-Akhangaran, Mirzachul, and Zarafshan physicogeographical districts. An.
pulcherrimus is common in the plain river valleys, except in the Qashqadaryo
physicogeographical district. An. martinius is found in the Qashqadaryo and
Nizhneamudryo physicogeographical districts. Livestock houses are the most
attractive day's rests for mosquitoes; utility rooms rank next in mosquito
density. Housing premises are slightly occupied by mosquitoes. The maximum size
of aggressive mosquitoes is noted in July, August, and early September.
PMID- 25850309
TI - [The spatial distribution and infection of Culex pipiens L. mosquitoes with
Western Nile virus in the Volgograd region].
AB - The infection of Culex pipiens f. pipiens and Cx. pipiens f. molestus mosquitoes
with Western Nile virus was studied. Their taxonomic status was determined from
the type of mitochondrial DNA. Among 424 females individually examined, there
were 4 infected specimens: 3 pipens females gathered in the urban and suburban
open biotopes and one molestus female caught in the open urban biotope. Molestus
mitotype females were first detected in the suburban open biotopes. The possible
reasons for the wide colonization of molestus mosquitoes and its epidemic
consequences are discussed.
PMID- 25850310
TI - [Organization and epidemiological surveillance of Western Nile fever in case of
the Volgograd Region].
AB - Western Nile fever (WNF) is an arboviral infection of the most relevance to the
Volgograd Region. The observed decreasing incidence of WNF in 2001-2006, 2008,
and 2009 and a decline in the number of its severe forms are only suggestive of
the temporary regression of the epidemic process in the Volgograd Region. There
are prerequisites and forerunners for a complication of the epidemiological
Western Nile fever situation in the Volgograd Region. The goal of the
epidemiological survey of Western Nile fever is to provide necessary and
sufficient information for the analysis of the epidemiological situation and to
define a line of public health policy and actions when making managerial
decisions.
PMID- 25850311
TI - [Fleas of small mammals involved in the epizootic process in the Gorno-Altaisk
natural focus of plague].
PMID- 25850312
TI - [Pyrethroid resistance in human lice (Anoplura, Pediculidae): toxicological and
molecular genetic methods].
AB - The paper gives the data obtained in toxicological experiments versus analysis by
a real-time polymerase chain reaction assay in permethrin-resistant human lice
(VSSC1 gene kdr mutations leading to the amino acid replacements T9171 and L920F
have been found). It is shown that the results of toxicological experiments may
be indirectly indicative of the genetic composition of a study sample of lice.
PMID- 25850313
TI - [Pneumocystosis as a nosocomial infection].
PMID- 25850314
TI - [Comparative efficacy of original oil escazole and nemozole suspensions in albino
mice with experimental trichinosis in the muscle phase of invasion].
AB - The efficacy of original oil escazole and nemozole suspensions in albino mice in
the muscle phase of T. spiralis invasion, which was detected by lifetime
diagnosis of experimental trichinosis 6 days after initiation of treatment in a
daily dose of 0.3 g/kg, was 100%. Under equal experimental conditions, the oil
nemozole suspension showed high toxicity and caused death in 50% of the treated
animals.
PMID- 25850315
TI - [Novel bromine-containing salicylanilides (the compounds MST-36 and MST-38).
Preparation and antihymenolepic activity].
PMID- 25850316
TI - [Evaluation of the antihymenolepic activity of a number of chlorinated and
brominated salicylanilide derivatives].
PMID- 25850317
TI - [Immunochemical properties of the excretory-secretory antigen of Trichinella
spiralis].
AB - In vitro cultivation of Trichinella spiralis provided data on the structure of
somatic and excretory-secretory antigens of T. spiralis larvae, their
immunochemical properties were studied. The findings suggest that work should be
continued to produce monoclonal antibodies and to develop highly sensitive and
specific ELISA test systems for the diagnosis of human and animal trichinosis.
PMID- 25850318
TI - [New evidence for the spread of Thelazia callipaeda in the Far East].
AB - Thelazia callipaeda nematodes parasitize in the eyes of domestic and wild
carnivorous mammals (more often in Canidae). Numerous cases of human infestation
are also known. The nematode spreads in South and East Asia although in the last
decade this has been reported from dogs, cats and wolves in South and Central
Europe as well. In the Russian Federation, T. callipaeda was earlier observed in
dogs, cats, foxes and raccoon dogs in some regions of the Russian Far East. Two
cases of human infestation were also reported. There has been no evidence of T.
callipaeda in Russia in the past 50 years. Postmortem parasitological surveys of
various wild carnivores were performed in the Primorsky Territory of Russia in
the winter of 2012 to the summer of 2014. Conjunctival sac including the space
under the nictitating membrane was sought for nematodes. T. callipaeda was
detected in 28 sables of the 492 examined ones, in 5 out of the 11 raccoon dogs,
in 2 out of the 3 foxes, and in one lynx. The examination of 25 kolinskies, 4
American minks, 3 Amur leopard cats, 2 yellow-throated martens and one badger
provided negative results. The sable and the wild lynx are firstly reported as
hosts of T. callipaeda. The findings suggest that there is a persisting natural
reservoir of zoonotic thelaziosis in the Russian Far East. The epidemiological
importance of this fact should not be underestimated.
PMID- 25850319
TI - [Optimization of a model evaluating the efficiency of methods for sanitary
helminthological examination of soil for its contamination with parasites].
PMID- 25850320
TI - [Novel rapid method for examination of soil for helminth eggs].
PMID- 25850321
TI - [A case of anisakidosis associated with Blastocyst invasion].
PMID- 25850322
TI - [The network model is an effective form of training preventive medicine
physicians (in case of medical parasitologists)].
AB - Professional medical education is most cost-based when training highly skilled
personnel. This is associated with expensive material and technical resources and
a high labor-to-output ratio of practicing programs. The network model makes it
possible to blaze new trails to achieve the quality of training the staff and the
governmental support of its educational programs strengthens the coordination
between higher educational establishments, research organizations, and
professional learning communities. By using the training of medical
parasitologists as an example, the paper shows a network model how to implement
the educational program.
PMID- 25850323
TI - [Methodical features of the molding of diagnostic competences in medical
parasitology workers].
AB - The paper provides a rationale for a procedure to mold diagnostic competences in
medical workers of the laboratories of therapeutic-and-prophylactic institutions
and hygiene and epidemiology centers, Russian Federal Service for Supervision of
Consumer Rights Protection and Human Welfare. The methodical features of molding
diagnostic competences in the above contingents are the design and organization
of an educational process by applying systems integration and competence-based
approaches; increased active self-directed learning of audience; a procedure to
organize its unsupervised extracurricular activities. Professional habits and
skills in laboratory specialists should be molded on the basis of didactic
principles and in compliance with the found methodical patterns. The eventual
result (molded competences) and its compliance with the practical health care
requirements is assessed using all control types (incoming, running,
intermediate, and ultimate ones). This ensures the stability and predictability
of molding diagnostic competences in parasitology specialists.
PMID- 25850324
TI - [The draft new World Health Organization program "global technical strategy for
malaria control and elimination for 2016-2025"].
PMID- 25850325
TI - The pathogenesis of atherosclerosis: a critical evaluation of the evidence.
AB - The consistent topography, transmural involvement, and variation in severity and
rate of progression in individual atherosclerotic lesions collectively indicate
the dominant, primary role of hemodynamics. Specific anatomic configurations,
vessels with elevated pressure, high velocity, or disturbed flow and iatrogenic
production of accelerated atherosclerosis and its complications in therapeutic
venous bypass grafts and arteriovenous shunts point to this role. The morphology
and complications are consistent with the loss of cohesion and tensile strength
of mural constituents and irreconcilably different from those of cholesterol- or
fat-overfed animals and from other metabolic lipid storage disorders. These
observations preclude dietary and circulating humoral factors and negate
currently prevailing etiologic hypotheses that do not account for topography,
pathogenesis, or complications. Atherosclerosis is the response to
hemodynamically induced repetitive tensile stresses due to the pulse pressure and
lesser flow-generated vibrations resulting in bioengineering fatigue occasioned
by cumulative molecular fragmentation of mural constituents. This phenomenon also
accounts for free-radical formation and lipoperoxidation. Atherosclerosis thus
constitutes the combined manifestations of tissue fatigue and compensatory
repair. When fatigue predominates, mural failure leads to the development of the
primary complications (mural tears, dissection, ectasia, tortuosity, aneurysms).
Lipid accumulation and thromboembolism are secondary phenomena. Fatigue onset is
enhanced by hypertension and acquired or inherited defects of individual mural
constituents. Iatrogenic and experimental production of atherosclerosis, its
pathogenesis, and complications by hemodynamic means provides the ultimate proof
of the causal role of bioengineering fatigue.
PMID- 25850326
TI - Pulmonary artery rupture as a complication of pulmonary hypertension: report of a
case and review of the literature.
AB - A 57-year-old woman with severe thromboembolic pulmonary hypertension died
suddenly, approximately 3 hours after pulmonary angiography. Autopsy revealed a
hemopericardium (350 mL) due to rupture of the pulmonary artery. Three acute
partial intimal-medial tears also were observed. Fatal rupture of the mediastinal
pulmonary arteries is a rare complication of severe pulmonary hypertension. A
review of eight similar cases indicates that rupture tends to occur in patients
with systemic levels of pressure, thrombotic (rather than plexogenic) forms of
pulmonary hypertension, and survival longer than two years (mean, 4.5 years) from
diagnosis.
PMID- 25850327
TI - Trypanosoma cruzi Infection Induces Myocardial Nitric Oxide Synthase.
AB - Chagas' disease caused by Trypanosoma cruzi, is an important cause of myocarditis
and cardiomyopathy. Acute and chronic infection is associated with myocardial
dysfunction, including dysrhythmias, conduction disturbances, and congestive
heart failure. Nitric oxide (NO) has been implicated in the myocardial
dysfunction associated with diseases of the myocardium. The inducible form of
nitric oxide synthase (iNOS) mediates the synthesis of NO and L-citrulline from L
arginine. An abundance of iNOS mRNA by Northern blot and a marked expression of
iNOS protein by Western blot was demonstrated in the myocardium of mice 30 days
postinfection with the Brazil strain of T. cruzi. Immunocytochemical staining of
the myocardial sections from infected mice also revealed the expression of iNOS.
Consistent with these observations, the myocardial L-citrulline content was
higher in infected mice, confirming NO expression in vivo. In addition, Northern
blot analysis revealed that interleukin-1beta (IL-1beta) and tumor necrosis
factor-alpha (TNF-alpha) mRNA were induced during infection. These data suggest
that the myocardial cytokine-iNOS pathway may be an important factor in the
pathogenesis of chagasic heart disease. In addition, this pathway may be a
potential target of future pharmacologic intervention.
PMID- 25850328
TI - Cardiac valve interstitial cells: regulator of valve structure and function.
AB - Cardiac valve interstitial cell tissue is present throughout the valve. The
molecular biology of this cell type is not well known. The purpose of this review
is to present our current understanding of the structure and function of valvular
interstitial cells and to describe experimental approaches available to study the
structure and regulation of interstitial cell function and the interaction of
interstitial cells with the valve matrix and with the surface endocardial
endothelial cells. Data available to date suggest that valvular interstitial
cells are contractile, have some of the characteristic features of smooth-muscle
cells, communicate with each other, secrete valvular matrix, regulate repair
processes following valve injury, and exhibit heterogeneous phenotypes. Further
studies are required to understand the regulation of structure and function of
these cells in both health and disease. This information will indeed be useful in
preventing valvular disease, in improving the design of therapeutic surgical
valve reconstruction, and in designing prosthetic valves.
PMID- 25850329
TI - Kawasaki disease: sudden death in early infancy from accelerated late sequelae of
coronary artery aneurysms.
AB - Kawasaki disease is an acute, self-limited illness of young children (most
commonly under 4 years of age) that may result in significant cardiovascular
sequelae in about 20% of the patients 10 to 20 years later, mostly from occlusive
coronary artery disease and myocardial infarction. Early mortality occurs in
about 2% of children under the age of 2 years as the result of acute coronary
vasculitis, with or without myocarditis, and of complications from coronary
aneurysms. To our knowledge, fatal late sequelae of "healed" or "regressed"
coronary aneurysms with occlusive intimal fibrocellular proliferation occurring
in children under 1 year of age, have not been reported. We describe one such
rare example in an 11-month-old infant.
PMID- 25850330
TI - Eye Movements Reveal the Influence of Event Structure on Reading Behavior.
AB - When we read narrative texts such as novels and newspaper articles, we segment
information presented in such texts into discrete events, with distinct
boundaries between those events. But do our eyes reflect this event structure
while reading? This study examines whether eye movements during the reading of
discourse reveal how readers respond online to event structure. Participants read
narrative passages as we monitored their eye movements. Several measures revealed
that event structure predicted eye movements. In two experiments, we found that
both early and overall reading times were longer for event boundaries. We also
found that regressive saccades were more likely to land on event boundaries, but
that readers were less likely to regress out of an event boundary. Experiment 2
also demonstrated that tracking event structure carries a working memory load.
Eye movements provide a rich set of online data to test the cognitive reality of
event segmentation during reading.
PMID- 25850331
TI - Standard short-term diet ameliorates the lipid profile altered by a fructose-rich
diet in rats.
AB - Markers of metabolic abnormalities are commonly found in rodents fed a fructose
rich diet. The purpose of this study was to determine whether the administration
of a short-term standard diet to rats is able to improve the lipid profile
altered by a fructose-rich diet. The male pups, immediately after birth, were
divided in three groups according to the diet for 90 days. Standard diet: a
standard diet for the whole experimental period; fructose (60% fructose-rich
diet): fructose-rich diet during the entire experimental period;
fructose/standard (FS): fructose-rich diet from the neonatal period up to 60 days
of age and standard diet from 60 to 90 days of age. A fructose-rich diet from the
neonatal period to 60 days reduced weight gain (P<0.05), as well as the weight of
adipose tissues in all the regions analyzed (epididymal, mesenteric,
retroperitoneal and posterior subcutaneous), and it altered the lipid profile
(elevation of triglycerides, total cholesterol, low density lipoprotein (LDL)
cholesterol and very low density lipoprotein (VLDL) cholesterol; P<0.05). When a
standard diet was administered after the fructose-rich diet, it was able to
partially reverse changes to the lipid profile, as total cholesterol levels were
significantly different in all the groups (P<0.05), and triglyceride and VLDL
cholesterol levels were similar between the control and FS group. In summary, a
fructose-rich diet altered the lipid profile, and a standard diet can partially
reverse the changed parameters in short term.
PMID- 25850332
TI - Regional cortical atrophy in depression and neurocognitive disorders.
PMID- 25850333
TI - Changed in translation: mRNA recoding by -1 programmed ribosomal frameshifting.
AB - Programmed -1 ribosomal frameshifting (-1PRF) is an mRNA recoding event commonly
utilized by viruses and bacteria to increase the information content of their
genomes. Recent results have implicated -1PRF in quality control of mRNA and DNA
stability in eukaryotes. Biophysical experiments demonstrated that the ribosome
changes the reading frame while attempting to move over a slippery sequence of
the mRNA--when a roadblock formed by a folded downstream segment in the mRNA
stalls the ribosome in a metastable conformational state. The efficiency of -1PRF
is modulated not only by cis-regulatory elements in the mRNA but also by trans
acting factors such as proteins, miRNAs, and antibiotics. These recent results
suggest a molecular mechanism and new important cellular roles for -1PRF.
PMID- 25850334
TI - A focus on the biosynthesis and composition of cuticle in fruits.
AB - Cuticles are plant structures, composed mostly by lipidic layers, synthesized by
nonwoody aerial plant organs and deposited on the surface of outer epidermal cell
walls. Although its significance has been often disregarded, cuticle deposition
modifies organ chemistry, influences mechanical properties, and plays a central
role in sensing and interacting with the surrounding environment. Even though
some research has been undertaken addressing cuticle biosynthesis and composition
in vegetative plant tissues, comparatively less information is available
regarding cuticle composition in the epidermis of fruits. However, recent work
points to a role for cuticles in the modulation of fruit quality and postharvest
performance, indicating that current models for the investigation of fruit
development, metabolism, and quality need to integrate a comprehensive knowledge
of the cuticle layer. This paper provides an overview of recent findings and
observations regarding cuticle biosynthesis and composition in fruits from
species of agronomic and economic relevance. Important, but often neglected
differences in cuticle composition and biosynthesis patterns among diverse fruit
species are described herein to generate an atlas of what is currently known
about fruit cuticles and to highlight what remains to be explored. Emphasis is
placed on the need to investigate each genetic background considering its own
specificities, to permit correlations with the particular physiology of each
species considered. Both specific composition and changes during maturation and
ripening are reviewed.
PMID- 25850335
TI - Feasibility of smartphone diaries and personal dosimeters to quantitatively study
exposure to ultraviolet radiation in a small national sample.
AB - BACKGROUND: In 2007, a national skin cancer prevention campaign was launched to
reduce the UV exposure of the Danish population. To improve campaign evaluation a
questionnaire validation using UV-dosimeters was initiated. AIM: To show the
feasibility of dosimeters for national representative studies and of smartphones
as a data collection tool. MATERIALS AND METHODS: Participants were sent a
dosimeter which they wore for 7 days, received a short diary questionnaire by
text message each day and subsequently a longer questionnaire. Correlation
between responses from questionnaire, smartphone diaries and dosimeters were
examined. RESULTS: This study shows a 99.5% return rate (n = 205) of the
dosimeters by ordinary mail and high response-rates for a smartphone
questionnaire dairy. Correlation coefficients for outdoor-time reported through
smartphones and dosimeters as average by week 0.62 (0.39-0.77), P < 0.001 (n =
40). Correlation coefficient for outdoor time estimated by questionnaire and
dosimeters were 0.42 (0.11-0.64), P = 0.008. The subjective perception of the
weather was the only covariate significantly influencing questionnaire estimates
of actual outdoor exposure. We showed that dosimeter studies are feasible in
national settings and that smartphones are a useful tool for monitoring and
collecting UV behavior data. CONCLUSION: We found diary data reported on a daily
basis through smartphones more strongly associated with actual outdoor time than
questionnaire data. Our results demonstrate tools and possible considerations for
executing a UV behavior questionnaire validation.
PMID- 25850336
TI - The loleva oral and written language test: psychometric properties.
AB - LolEva, a computerized test for ages 3 to 8 years old, identifies issues in the
development of skills that can lead to reading acquisition difficulties. Its
structure captures two distinct areas: Phonological Awareness (PA, seven
subtests: rhyme, identification-addition-omission of syllable and phoneme at the
beginning and end of a word), and Initial Reading Competence (IRC, six subtests:
reading uppercase and lowercase letters, simple words, complex words, and
pseudowords, and word segmentation). With results collected in a sample of 341
children with the target ages and attending public or private schools, the alpha
coefficient was .94 for PA, and .92 for IRC. Factor analysis indicated three
factors are present (performance on PA and IRC, and word reading times), together
explaining 75% of variance, providing evidence to support the construct validity
of the test. On the other hand, analysis of variance showed significant
differences for year-in-school variable for PA subscale, F(4, 336) = 191.385, p <
.001, eta2 p = .695, 1-beta = 1.0, as well as for IRC subscale, both in number of
correct answers, which increased as schooling progressed: F(4, 336) = 197.897, p
< .001, eta2 p = .702, 1-beta = 1.0, and task completion time, which decreased as
education progressed: F(4, 335) = 47.048, p < .001, eta2 p = .360, 1-beta = 1.0.
Also, PA repeated measures analysis revealed that was easier Identification than
Addition and Omission , F(2, 672) = 31.639, p < .001, eta2 p = .086, 1-beta =
1.0, syllable-related tasks than phoneme-related task, F(1, 336) = 229.000, p <
.001, eta2 p = .405, 1-beta = 1.0, and syllable or phoneme at the end of the word
than at the beginning, F(1, 336) = 59.201, p < .001, eta2 p = .150, 1-beta = 1.0.
Moreover, all items were examined and indexes of difficulty and discrimination
were obtained.
PMID- 25850337
TI - Serial measurements of serum thyroglobulin in response to recombinant human
thyrotropin stimulation.
PMID- 25850338
TI - Neuropsychological performance in treatment-seeking Operation Enduring
Freedom/Operation Iraqi Freedom Veterans with a history of mild traumatic brain
injury.
AB - INTRODUCTION: Clinical neuropsychological presentation of treatment-seeking
Veterans with a remote history of mild traumatic brain injury (mTBI) is widely
variable. This manuscript seeks to better characterize cognitive concerns in the
post-acute phase following mTBI and to identify the neuropsychological profiles
of a large sample of clinically referred Operation Enduring Freedom/Operation
Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) Veterans with a history of mTBI
and current cognitive complaints. We hypothesized that a minority of cases would
exhibit valid and widespread neuropsychological deficits. METHOD: Retrospective
chart reviews of neuropsychological testing and mental health symptoms and
diagnoses were conducted on 411 clinically referred OEF/OIF/OND Veterans with a
history of mTBI. Groups were created based on scores on performance validity
measures and based on overall neuropsychological performance. RESULTS: A total of
29.9% of the sample performed below normative expectations on at least one
performance validity test (PVT). Of those Veterans performing adequately on PVTs,
60% performed within normal limits on virtually all neuropsychological measures
administered, leaving only 40% performing below expectations on two or more
measures. Mood and neurobehavioral symptoms were significantly elevated in
Veterans performing below cutoff on PVTs compared to Veterans who performed
within normative expectations or those with valid deficits. Neurobehavioral
symptoms were significantly correlated with mental health symptom reports but not
with injury variables. CONCLUSIONS: In summary, in a large sample of clinically
referred Veterans with persistent cognitive complaints after mild TBI, a third
demonstrated invalid clinical neuropsychological testing, and, of those
performing at or above cutoff on PVTs, over half performed within normative
expectations across most neuropsychological tests administered. Results highlight
the importance of objective assessment of cognitive functioning in this
population as subjective reports do not correspond to objective assessment in the
majority of cases.
PMID- 25850339
TI - Relative contributions of the major human CYP450 to the metabolism of icotinib
and its implication in prediction of drug-drug interaction between icotinib and
CYP3A4 inhibitors/inducers using physiologically based pharmacokinetic modeling.
AB - OBJECTIVE: Icotinib is an anticancer drug, but relative contributions of CYP450
have not been identified. This study was carried out to identify the contribution
percentage of CYP450 to icotinib and use the results to develop a physiologically
based pharmacokinetic (PBPK) model, which can help to predict drug-drug
interaction (DDI). METHODS: Human liver microsome (HLM) and supersome using
relative activity factor (RAF) were employed to determine the relative
contributions of the major human P450 to the net hepatic metabolism of icotinib.
These values were introduced to develop a PBPK model using SimCYP. The model was
validated by the observed data in a Phase I clinical trial in Chinese healthy
subjects. Finally, the model was used to simulate the DDI with ketoconazole or
rifampin. RESULTS: Final contribution of CYP450 isoforms determined by HLM showed
that CYP3A4 provided major contributions to the metabolism of icotinib. The
percentage contributions of the P450 to the net hepatic metabolism of icotinib
were determined by HLM inhibition assay and RAF. The AUC ratio under concomitant
use of ketoconazole and rifampin was 3.22 and 0.55, respectively. CONCLUSION:
Percentage of contribution of CYP450 to icotinib metabolism was calculated by
RAF. The model has been proven to fit the observed data and is used in predicting
icotinib-ketoconazole/rifampin interaction.
PMID- 25850340
TI - Anti-proliferative effect of Fe(III) complexed with 1-(2-hydroxy-3
methoxybenzaldehyde)-4-aminosalicylhydrazone in HepG2 cells.
AB - We previously developed a chelating ligand, 1-(2-hydroxy-3-methoxybenzaldehyde)-4
aminosalicylhydrazone (HMB-ASH), which can chelate Fe(III) to form a complex. The
HMB-ASH-Fe(III) complex exhibits a dose-dependent anti-proliferative effect in
HepG2 cells, whereas the ligand, HMB-ASH, and Fe(III) alone had no considerable
effect. The HMB-ASH-Fe(III) complex was composed of Fe(III):HMB-ASH (1:2), as
determined by high-performance liquid chromatography with high-resolution mass
spectrometry. The IC50 value was approximately 20 MUM, which was comparable to
those of the anti-cancer drugs oxaliplatin (OXP) and etoposide (ETP) under the
same conditions. Similar to OXP and ETP, HMB-ASH-Fe(III) induced apoptosis in
HepG2 cells, as revealed by terminal deoxynucleotidyl transferase fluorescein-12
dUTP nick end labeling assay.
PMID- 25850341
TI - Association of overexpression of efflux pump genes with antibiotic resistance in
Pseudomonas aeruginosa strains clinically isolated from urinary tract infection
patients.
AB - There are several mechanisms for antibiotic-resistant Pseudomonas aeruginosa. The
purpose of this study is to investigate the association between the expression of
efflux pump-coding genes and antibiotic resistance in P. aeruginosa causing
urinary tract infections (UTIs). We extracted the RNA from 105 clinical strains
of P. aeruginosa isolated from UTI patients with full data on antibiotic MICs and
assayed real-time quantitative reverse-transcription PCR. We investigated the
gene expressions of four resistance nodulation cell division-type multi-drug
efflux pump systems (MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY(-OprA)) and the
correlation of the MICs of nine antibiotics, risk factors and antibiotic
resistance-related genes with expressions of mexB, mexC, mexE and mexY.
Multivariate statistical data demonstrated a significant relationship between
increased expression of mexB or mexC and complicated UTI (Odds ratio=8.03,
P<0.001 and Odds ratio=8.86, P=0.032, respectively). We also found a significant
association between the increased expression of mexC and resistance to
levofloxacin (LVFX) (Odds ratio=4.48, P=0.035). In conclusion, increased
expression of mexC leads to LVFX resistance in P. aeruginosa causing UTI. These
results contribute to our knowledge of the efflux pump system and antibiotic
resistance.
PMID- 25850342
TI - Antimicrobial resistance surveillance of doripenem in China.
AB - To investigate the antibacterial resistance to doripenem in China and to
understand the distribution trends of resistant bacteria. All the clinical
isolates were collected from hospitals and the susceptibility tests were
performed using the agar dilution method recommended by the Clinical Laboratory
Standards Institute (CLSI) central laboratory. The susceptibility of the isolates
to antimicrobial agents was determined using the CLSI (2014) or European
Committee on Antimicrobial Susceptibility Testing (EUCAST) (2013) guidelines. A
total of 4047 pathogenic strains were isolated from 18 tertiary hospitals in 18
cities across China between July 2011 and June 2012. MIC results indicated that
the vast majority of Enterobacteriaceae maintained high susceptibility to
doripenem, with a lower resistance rate (1.9%) than that observed for other drugs
tested. In the case of non-fermenting Gram-negative isolates, the resistance rate
of Pseudomonas aeruginosa was 16.2%, which was less than that of imipenem and
meropenem, and the Acinetobacter baumannii doripenem resistance rate was 67.4%.
Doripenem also showed good in vitro activity against other the bacteria tested.
This study suggests that the gradual increase in carbapenem nonsusceptible
Enterobacteriaceae should be monitored carefully alongside the increasing
multidrug-resistant and extensively drug-resistant A. baumannii.
PMID- 25850344
TI - Liver myeloid-derived suppressor cells expand in response to liver metastases in
mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T.
AB - Chimeric antigen receptor-modified T cell (CAR-T) technology, a promising
immunotherapeutic tool, has not been applied specifically to treat liver
metastases (LM). While CAR-T delivery to LM can be optimized by regional
intrahepatic infusion, we propose that liver CD11b+Gr-1+ myeloid-derived
suppressor cells (L-MDSC) will inhibit the efficacy of CAR-T in the intrahepatic
space. We studied anti-CEA CAR-T in a murine model of CEA+ LM and identified
mechanisms through which L-MDSC expand and inhibit CAR-T function. We established
CEA+ LM in mice and studied purified L-MDSC and responses to treatment with
intrahepatic anti-CEA CAR-T infusions. L-MDSC expanded threefold in response to
LM, and their expansion was dependent on GM-CSF, which was produced by tumor
cells. L-MDSC utilized PD-L1 to suppress anti-tumor responses through engagement
of PD-1 on CAR-T. GM-CSF, in cooperation with STAT3, promoted L-MDSC PD-L1
expression. CAR-T efficacy was rescued when mice received CAR-T in combination
with MDSC depletion, GM-CSF neutralization to prevent MDSC expansion, or PD-L1
blockade. As L-MDSC suppressed anti-CEA CAR-T, infusion of anti-CEA CAR-T in
tandem with agents targeting L-MDSC is a rational strategy for future clinical
trials.
PMID- 25850345
TI - Advances in hepatology: 2015.
PMID- 25850343
TI - My 65 years in protein chemistry.
AB - This is a tour of a physical chemist through 65 years of protein chemistry from
the time when emphasis was placed on the determination of the size and shape of
the protein molecule as a colloidal particle, with an early breakthrough by James
Sumner, followed by Linus Pauling and Fred Sanger, that a protein was a real
molecule, albeit a macromolecule. It deals with the recognition of the nature and
importance of hydrogen bonds and hydrophobic interactions in determining the
structure, properties, and biological function of proteins until the present
acquisition of an understanding of the structure, thermodynamics, and folding
pathways from a linear array of amino acids to a biological entity. Along the
way, with a combination of experiment and theoretical interpretation, a mechanism
was elucidated for the thrombin-induced conversion of fibrinogen to a fibrin
blood clot and for the oxidative-folding pathways of ribonuclease A. Before the
atomic structure of a protein molecule was determined by x-ray diffraction or
nuclear magnetic resonance spectroscopy, experimental studies of the fundamental
interactions underlying protein structure led to several distance constraints
which motivated the theoretical approach to determine protein structure, and
culminated in the Empirical Conformational Energy Program for Peptides (ECEPP),
an all-atom force field, with which the structures of fibrous collagen-like
proteins and the 46-residue globular staphylococcal protein A were determined. To
undertake the study of larger globular proteins, a physics-based coarse-grained
UNited-RESidue (UNRES) force field was developed, and applied to the protein
folding problem in terms of structure, thermodynamics, dynamics, and folding
pathways. Initially, single-chain and, ultimately, multiple-chain proteins were
examined, and the methodology was extended to protein-protein interactions and to
nucleic acids and to protein-nucleic acid interactions. The ultimate results led
to an understanding of a variety of biological processes underlying natural and
disease phenomena.
PMID- 25850347
TI - Current management of acute liver failure.
AB - PURPOSE OF REVIEW: Acute liver failure (ALF) is a rare but life-threatening
systemic disorder. Survival rates with or without emergency liver transplantation
(ELT) are increasing. The benefit of ELT in some cases has been questioned and
the potential for survival with medical management alone is changing our approach
to the management of this disease. RECENT FINDINGS: Survival rates for all causes
of ALF are increasing because of improvements in the care of the critically ill
patient. A multifactorial approach involving support of respiratory, circulatory
and renal function together with measures to avoid intracranial hypertension,
metabolic disequilibrium and sepsis are required. For those who do not respond to
these measures or specific antidotes, the selection methods for those likely to
benefit from transplantation remain imperfect and novel methods based on the
prediction of hepatic regeneration are required. For patients with ALF secondary
to acetaminophen overdose, some experts believe a randomized controlled trial is
required to find those most likely to benefit from ELT. SUMMARY: ALF remains a
life-threatening condition with a high mortality rate requiring prompt support of
multiorgan failure. Historical listing criteria for ELT are being questioned and
improvement in medical management offers the option of continued improvements in
transplant-free survival.
PMID- 25850346
TI - Aging and liver disease.
AB - PURPOSE OF REVIEW: Aging is a condition in which a person gradually loses the
ability to maintain homeostasis, due to structural alteration or dysfunction.
Aging is a major risk factor for most chronic diseases. As the liver has a
remarkable ability to regenerate, this review assessed the effect of aging on
clinical liver disease with references to preclinical models when relevant to
pathogenesis. RECENT FINDINGS: Aging has been shown to not only enhance
vulnerability to acute liver injury but also increase susceptibility of the
fibrotic response. Aging is associated with the severity and poor prognosis of
various liver diseases including nonalcoholic fatty liver disease, alcoholic
liver disease, hepatitis C, and liver transplantation. SUMMARY: Treatment of
older patients with liver disease may require different or longer interventions.
Transplantation of an older liver will be less tolerant of subsequent injury.
Future studies are needed to understand more about the molecular mechanism of
aging and contribute to the development of a noble treatment strategy that can
block the progression of aging-induced liver diseases.
PMID- 25850348
TI - Human pluripotent stem cell-derived cholangiocytes: current status and future
applications.
AB - PURPOSE OF REVIEW: Pluripotent stem cells, such as embryonic stem cells and
inducible pluripotent stem (iPS) cells, have high proliferative multipotency for
differentiation into mature functional cells that are useful for treatment and
basic research on several diseases. Cholangiocytes are differentiated from fetal
hepatic progenitor cells (hepatoblasts) and are important for transport of bile
acids that are synthesized by mature hepatocytes in the liver. However, the
molecular mechanisms of development and function of human cholangiocytes remain
unknown. This review mentions the potential of human cholangiocytic culture from
pluripotent stem cells to contribute to the analyses of the human bile duct
system and diseases. RECENT FINDINGS: Recent studies found that human hepatic
cholangiocytic cells can be differentiated from human embryonic stem and iPS
cells in a suitable culture condition. Cholangiocytic cysts have epithelial cell
polarity formed in a three-dimensional cell culture system using extracellular
matrices. SUMMARY: Disease pathogenesis was elucidated in vitro using
differentiated cells from disease-related iPS cells. Using genome-editing
enzymes, iPS cells with disease-specific gene mutations can be easily and rapidly
established. These disease-related iPS cells and cholangiocytic culture system
may be useful for analyses and drug screening of human bile duct diseases.
PMID- 25850353
TI - Compound heterozygous C282Y/Q283P and Q283P/H63D mutations in haemochromatosis.
PMID- 25850350
TI - Mild cognitive impairment is associated with poorer decision-making in community
based older persons.
AB - OBJECTIVE: To test the hypothesis that mild cognitive impairment (MCI) is
associated with poorer financial and healthcare decision-making. DESIGN:
Community-based epidemiological cohort study. SETTING: Communities throughout
northeastern Illinois. PARTICIPANTS: Older persons without dementia from the Rush
Memory and Aging Project (N = 730). MEASUREMENTS: All participants underwent a
detailed clinical evaluation and decision-making assessment using a measure that
closely approximates materials used in real-world financial and healthcare
settings. This allowed for measurement of total decision-making and financial and
healthcare decision-making. Regression models were used to examine whether MCI
was associated with a lower level of decision-making. In subsequent analyses, the
relationship between specific cognitive systems (episodic memory, semantic
memory, working memory, perceptual speed, visuospatial ability) and decision
making was explored in participants with MCI. RESULTS: MCI was associated with
lower total, financial, and healthcare decision-making scores after accounting
for the effects of age, education, and sex. The effect of MCI on total decision
making was equivalent to the effect of more than 10 additional years of age.
Additional models showed that, when considering multiple cognitive systems,
perceptual speed accounted for the most variance in decision-making in
participants with MCI. CONCLUSION: Persons with MCI may have poorer financial and
healthcare decision-making in real-world situations, and perceptual speed may be
an important contributor to poorer decision-making in persons with MCI.
PMID- 25850355
TI - The collision tumor in the assessment of non-melanoma skin cancer caused by
occupational UV exposure.
PMID- 25850354
TI - Influences of hormone replacement therapy on olfactory and cognitive function in
postmenopausal women.
AB - Olfactory dysfunction can be an early sign of Alzheimer's disease. Since hormone
replacement therapy (HRT) may protect against Alzheimer's disease in
postmenopausal women, the question arises as to whether it also protects against
olfactory dysfunction in such women. A total of three olfactory and 12
neurocognitive tests were administered to 432 healthy postmenopausal women with
varied HRT histories. Serum levels of reproductive hormones were obtained for all
subjects; APOE-epsilon4 haplotype was determined for 77 women. National Adult
Reading Test and Odor Memory/Discrimination Test scores were positively
influenced by HRT. Odor Identification and Odor Memory/Discrimination Test scores
were lower for women who scored poorly on a delayed recall test, a surrogate for
mild cognitive impairment. The Wechsler Adult Intelligence Scale, Revised, as a
Neuropsychological Instrument Spatial Span Backwards Test scores were higher in
women receiving estrogen and progestin HRT and directly correlated with serum
testosterone levels, the latter implying a positive effect of testosterone on
spatial memory. APOE-epsilon4 was associated with poorer odor threshold test
scores. These data suggest that HRT positively influences a limited number of
olfactory and cognitive measures during menopause.
PMID- 25850356
TI - Neoflavonoid dalbergiphenol from heartwood of Dalbergia sissoo acts as bone
savior in an estrogen withdrawal model for osteoporosis.
AB - OBJECTIVE: Dalbergiphenol (DGP) is a neoflavonoid isolated from heartwood of
Dalbergia sissoo. Effects of DGP on skeletal health remain to be elucidated. The
objective of the present study was to investigate the biological effects of DGP
on bone loss in ovariectomized mice. METHODS: Adult BALB/c mice were
ovariectomized and administered DGP (1 and 5 mg/kg/d) or 17beta-estradiol (E2)
orally for 6 weeks. The sham group and the ovariectomy (OVX) + vehicle group
served as controls. Eight female BALB/c mice were taken for each group. Uterine
estrogenicity, bone microarchitecture, biomechanical strength, new bone formation
(based on bone formation rate and mineral apposition rate), and skeletal
expression of osteogenic and resorptive gene markers were studied. RESULTS: OVX
resulted in a marked increase in body weight and a decrease in femoral and
vertebral trabecular bone volume that were prevented by DGP or E2 treatment. DGP
treatment increased bone biomechanical strength and new bone formation rate in
ovariectomized mice, comparable with E2 treatment. However, increase in uterine
weight and estrogenicity were observed in E2-treated ovariectomized mice, but not
in response to DGP treatment. Treatment with DGP increased messenger RNA
expression of runt-related transcription factor 2, osterix, and collagen type I,
and decreased messenger RNA expression of tartrate-resistant acid phosphatase and
the osteoprotegerin-to-receptor activator of nuclear factor-kappaB ligand ratio
in the femur of ovariectomized mice. CONCLUSIONS: Overall findings suggest that
DGP treatment can effectively prevent OVX-induced increase in bone loss and
decrease in bone strength possibly by increasing osteoblastic activities and by
decreasing osteoclastic activities.
PMID- 25850357
TI - Failure to treat menopausal symptoms: a disconnect between clinical practice and
scientific data.
PMID- 25850358
TI - A facile and efficient synthesis of polystyrene/gold-platinum composite particles
and their application for aerobic oxidation of alcohols in water.
AB - Herein we develop a facile and effective method for the synthesis of composite
particles composed of polystyrene microspheres decorated with gold-platinum alloy
nanoparticles, which exhibited excellent catalytic activity and recyclability for
1-phenylethanol oxidation under mild conditions (without a base, air as an
oxidant, in water, at 40 degrees C).
PMID- 25850359
TI - Diffusion Tensor Imaging Adds Diagnostic Accuracy in Magnetic Resonance
Neurography.
AB - OBJECTIVE: The aim of this study was to determine whether quantitative diffusion
tensor imaging (DTI) adds diagnostic accuracy in magnetic resonance neurography.
MATERIALS AND METHODS: This prospective study was approved by the institutional
review board. We enrolled 16 patients with peripheral polyneuropathy of various
etiologies involving the upper arm and 30 healthy controls. Magnetic resonance
neurography was performed at 3 T using transverse T2-weighted (T2-w) turbo spin
echo and spin echo planar imaging diffusion-weighted sequences. T2-weighted
normalized signal (nT2), fractional anisotropy (FA), apparent diffusion
coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD) of the
median, ulnar, and radial nerves were quantified after manual segmentation.
Diagnostic performance of each separate parameter and combinations of parameters
was assessed using the area under the receiver operating characteristic curve
(AUC). Bootstrap validation was used to adjust for potential overfitting.
RESULTS: Average nT2, ADC, RD, and AD values of the median, ulnar, and radial
nerve were significantly increased in neuropathy patients compared with that in
healthy controls (nT2, 1.49 +/- 0.05 vs 1.05 +/- 0.05; ADC, 1.4 * 10(-3) +/- 2.8
* 10(-5) mm(2)/s vs 1.1 * 10(-3) +/- 1.3 * 10(-5) mm(2)/s; RD, 9.5 * 10(-4) +/-
2.9 * 10(-5) mm(2)/s vs 7.2 * 10(-4) +/- 1.3 * 10(-5) mm(2)/s; AD, 2.3 * 10(-3)
+/- 3.7 * 10(-5) mm(2)/s vs 2.0 * 10(-3) +/- 2.2 * 10(-5) mm(2)/s; P < 0.001 for
all comparisons). Fractional anisotropy values were significantly decreased in
patients (0.51 +/- 0.01 vs 0.59 +/- 0.01; P < 0.001). T2-weighted normalized
signal and DTI parameters had comparable diagnostic accuracy (adjusted AUC: T2-w,
0.92; FA, 0.88; ADC, 0.89; AD, 0.84; RD, 0.86). Combining DTI parameters
significantly improved the diagnostic accuracy over single-parameter analysis. In
addition, the combination of nT2 with DTI parameters yielded excellent adjusted
AUCs up to 0.97 (nT2 + FA). CONCLUSIONS: Diffusion tensor imaging has high
diagnostic accuracy in peripheral neuropathy. Combining DTI with T2 can
outperform T2-w imaging alone and provides added value in magnetic resonance
neurography.
PMID- 25850360
TI - The effect of bladder sensation on uroflowmetry parameters in healthy young men.
AB - AIMS: To investigate the effect of the bladder sensation grade on uroflowmetry
parameters. METHODS: Fifty healthy volunteering young men were enrolled in the
present study. In total, three uroflowmetry evaluations were made. Qmax , Qave ,
VV, and PVR urine was obtained three times in three described bladder sensation
grades, nearly at the same time of the day. RESULTS: The mean age of the
participants in the present study is 29.08 +/- 3.8 years. The mean Qmax values of
the volunteers were 17.4 +/- 4.8 ml/s, 24.1 +/- 6.0 ml/s, and 29.6 +/- 6.5 ml/s
in the first, second, and third, voiding desire grades, respectively. The mean
Qave values were 9.9 +/- 2.1 ml/s, 12.9 +/- 2.9 ml/s, and 15.9 +/- 4.0 ml/s for
each of the voiding desire grades mentioned. A statistically significant
difference was obvious for all three bladder sensation grades in terms of Qmax
and Qave values (P = 0.000). However, no statistically significant difference was
seen regarding the PVR urine volumes. The mean voided volume in the first, second
and third uroflowmetry were 140 +/- 42 ml, 245 +/- 64 ml, and 449 +/- 105 ml,
respectively. The highest Qmax and Qave values were obtained when the desire to
void was urgent. CONCLUSIONS: The findings of the study show that, uroflowmetry
evaluations are to be made if the patients have a strong desire to void. Only
thus the highest Qmax values can be obtained; yet, the degree of perceived
bladder sensation does not have a statistically significant impact on PVR
quantity. Neurourol. Urodynam. 35:622-624, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 25850361
TI - Transitions in the communication experiences of tracheostomised patients in
intensive care: a qualitative descriptive study.
AB - AIMS AND OBJECTIVES: To describe how tracheostomised patients in intensive care
experience acts of communication and to better understand their experiences in
the context of the transitions theory. BACKGROUND: Waking up in an intensive care
unit unable to speak because of mechanical ventilation can be challenging.
Communication aids are available, but patients still report difficulties
communicating. Investigating how mechanically ventilated patients experience
communication in the context of the transitions theory might elucidate new ways
of supporting them during their transitions while being ventilated. DESIGN: A
qualitative, descriptive design. METHODS: Eleven patients who had previously been
tracheostomised in an intensive care unit were included in this quality
improvement project conducted in a university hospital in Norway. Participants
were tracheostomised from 3-27 days. Semistructured interviews were conducted
from June 2013-August 2013, 3-18 months after hospital discharge. Transcripts
were analysed using inductive content analysis. RESULTS: Participants reported a
great diversity of emotions and experiences attempting to communicate while being
tracheostomised. One overarching theme emerging from the analysis was the
'Experience of caring and understanding despite having uncomfortable feelings due
to troublesome communication.' The theme consists of three categories. The
category 'Emotionally challenging' shows that patients struggled initially. With
time, their coping improved, as revealed in the category 'The experience changes
with time.' Despite difficulties, participants described positive experiences, as
shown in the category 'Successful communication.' CONCLUSION: The importance of
patients experiencing caring and understanding despite their difficult situation
constitutes the core finding. The findings suggest that participants went through
different transitions. Some reached the end of their transition, experiencing
increased stability. RELEVANCE TO CLINICAL PRACTICE: Despite challenges with
communication, participants reported that caring and safety provided by health
care professionals were significant experiences. They viewed nonverbal
communication as being very important.
PMID- 25850363
TI - President's report.
PMID- 25850362
TI - Recovery of Ventriculo-Atrial Conduction after Adrenaline in Patients Implanted
with Pacemakers.
AB - BACKGROUND: Ventriculo-atrial (VA) conduction can have negative consequences for
patients with implanted pacemakers and defibrillators. There is concern whether
impaired VA conduction could recover during stressful situations. Although the
influence of isoproterenol and atropine are well established, the effect of
adrenaline has not been studied systematically. The objective of this study was
to determine if adrenaline can facilitate recovery of VA conduction in patients
implanted with pacemakers. METHODS: A prospective study was conducted on 61
consecutive patients during a 4-month period (April-July 2014). The presence of
VA conduction was assessed during the pacemaker implantation procedure. In case
of an impaired VA conduction, adrenaline infusio was used as a stress surrogate
to test conduction recovery. RESULTS: The indications for pacemaker implantation
were: sinus node dysfunction in 18 patients, atrioventricular (AV) block in 40
patients, binodal dysfunction (sinus node+ AV node) in two patients and other
(carotid sinus syndrome) in one patient. In the basal state, 15/61 (24.6%)
presented spontaneous VA conduction and 46/61 (75.4%) had no VA conduction. After
administration of adrenaline, there was VA conduction recovery in 5/46 (10.9%)
patients. CONCLUSIONS: Adrenaline infusion produced recovery of VA conduction in
10.9% of patients with absent VA conduction in a basal state. Recovery of VA
conduction during physiological or pathological stresses could be responsible for
the pacemaker syndrome, PMT episodes, or certain implantable cardiac
defibrillator detection issues.
PMID- 25850364
TI - Should retention of a tooth be an important goal of dentistry? How do you decide
whether to retain and restore a tooth requiring endodontic treatment or to
extract and if possible replace the tooth?
AB - Whether a questionable tooth should be treated endodontically or extracted, is
still a dilemma clinicians encounter every day. With advances in technology such
as implantology, deciding whether or not to save a tooth is still not clear.
Local site-specific factors and patient-related factors that may affect the
longevity of a particular tooth should be considered in preparing the treatment
plan. Long-term success rates for root canal therapy and implant-supported crowns
demonstrate similar outcomes. A choice between these alone is not sufficient in
the decision-making process. Only following a systematic evaluation of the
reasons for and against tooth retention as directed by each individual case, can
the best option be decided.
PMID- 25850368
TI - Associate professor Giampiero Rossi-Fedele.
PMID- 25850369
TI - A novel set of microsatellite markers for the European Grapevine Moth Lobesia
botrana isolated using next-generation sequencing and their utility for genetic
characterization of populations from Europe and the Middle East.
AB - Using a high-throughput 454 pyrosequencing approach a novel set of microsatellite
markers was developed for one of the key grapevine insect pests, the European
grapevine moth Lobesia botrana (Lepidoptera: Tortricidae). 20 primer pairs
flanking a microsatellite motif were designed based on the sequences obtained and
were subsequently evaluated in a sample of 14 L. botrana populations from Europe
and the Middle East. 11 markers showed stable and reproducible amplification
patterns; however, one of the 11 markers was monomorphic in all L. botrana
populations analysed. Estimated frequencies of null alleles of more than 20% were
evident for two of the markers tested, but varied substantially depending on the
respective L. botrana population. In 12 of the 14 L. botrana populations observed
heterozygosities were lower to those expected under Hardy-Weinberg equilibrium,
indicating a deficiency of heterozygotes in the respective populations. The
overall F ST value of 0.075 suggested a moderate but significant genetic
differentiation between the L. botrana populations included in this study. In
addition, a clear geographic structure was detected in the set of samples,
evident through a significant isolation by distance and through results from
structure analysis. In structure analysis, L. botrana populations were grouped in
two clearly separated clusters according to their European (Spain, Italy,
Germany) or Middle Eastern (Israel, Syria, Turkey) origin. This novel set of
microsatellite markers can now be applied to study the evolutionary ecology of
this species including host shifts and host adaptation as well as spread of
individuals across worldwide viticulture.
PMID- 25850370
TI - A single high-resolution HLA mismatch has a similar adverse impact on the outcome
of related hematopoietic stem cell transplantation as a single low-resolution HLA
mismatch.
AB - The relative importance of the resolution level of HLA typing has not been fully
defined for related donor transplantation. To address this question, we
retrospectively evaluated patients who underwent a first related hematopoietic
stem cell transplantation (HSCT) from 2000 to 2011 from an HLA high-resolution
matched (MRD, n = 2,244), high-resolution 1 locus-mismatched (HR-MMRD, n = 116),
or low-resolution 1 locus-mismatched related donor (LR-MMRD, n = 396) in the
graft-versus-host direction at three loci (HLA A, B, and DRB1) using the database
of the Japan Society for Hematopoietic Cell Transplantation. The median age was
40 years (0-74). The median follow-up duration of surviving patients was 950
days. Although the cumulative incidences of grade III-IV acute graft-versus-host
disease (GVHD) in the HR-MMRD and LR-MMRD groups were significantly higher than
those in the MRD group (HR-MMRD 19.8%, LR-MMRD 20.4%, and MRD 9.5%), there was no
statistically significant difference between the HR-MMRD and LR-MMRD groups (P =
0.65). Although both HR-MMRD and LR-MMRD were significantly associated with an
increased risk of non-relapse mortality and a worse overall survival, there was
no statistically significant difference between the HR-MMRD and LR-MMRD groups.
In conclusion, LR-MM and HR-MM have a similar adverse impact on the outcome in
related HSCT.
PMID- 25850371
TI - Regional versus urban differences in teenage alcohol use: Does parental
disapproval account for these differences?
AB - OBJECTIVE: To investigate if parental disapproval of alcohol use accounts for
differences in adolescent alcohol use across regional and urban communities.
DESIGN: Secondary data analysis of grade-level stratified data from a random
sample of schools. SETTING: High schools in Victoria, Australia. PARTICIPANTS: A
random sample of 10 273 adolescents from Grade 7 (mean age = 12.51 years), 9
(14.46 years) and 11 (16.42 years). MAIN OUTCOME MEASURES: The key independent
variables were parental disapproval of adolescent alcohol use and regionality
(regional/ urban), and the dependent variable was past 30 days alcohol use.
RESULTS: After adjusting for potential confounders, adolescents in regional areas
were more likely to use alcohol in the past 30 days (OR = 1.83, 1.44 and 1.37 for
Grades 7, 9 and 11, respectively, P < 0.05), and their parents have a lower level
of disapproval of their alcohol use (b = -0.12, -0.15 and -0.19 for Grades 7, 9
and 11, respectively, P < 0.001). Bootstrapping analyses suggested that 8.37%,
23.30% and 39.22% of the effect of regionality on adolescent alcohol use was
mediated by parental disapproval of alcohol use for Grades 7, 9 and 11
participants respectively (P < 0.05). CONCLUSIONS: Adolescents in urban areas had
a lower risk of alcohol use compared with their regional counterparts, and
differences in parental disapproval of alcohol use contributed to this
difference.
PMID- 25850372
TI - Droplet digital polymerase chain reaction (PCR) outperforms real-time PCR in the
detection of environmental DNA from an invasive fish species.
AB - Environmental DNA (eDNA) has been used to investigate species distributions in
aquatic ecosystems. Most of these studies use real-time polymerase chain reaction
(PCR) to detect eDNA in water; however, PCR amplification is often inhibited by
the presence of organic and inorganic matter. In droplet digital PCR (ddPCR), the
sample is partitioned into thousands of nanoliter droplets, and PCR inhibition
may be reduced by the detection of the end-point of PCR amplification in each
droplet, independent of the amplification efficiency. In addition, real-time PCR
reagents can affect PCR amplification and consequently alter detection rates. We
compared the effectiveness of ddPCR and real-time PCR using two different PCR
reagents for the detection of the eDNA from invasive bluegill sunfish, Lepomis
macrochirus, in ponds. We found that ddPCR had higher detection rates of bluegill
eDNA in pond water than real-time PCR with either of the PCR reagents, especially
at low DNA concentrations. Limits of DNA detection, which were tested by spiking
the bluegill DNA to DNA extracts from the ponds containing natural inhibitors,
found that ddPCR had higher detection rate than real-time PCR. Our results
suggest that ddPCR is more resistant to the presence of PCR inhibitors in field
samples than real-time PCR. Thus, ddPCR outperforms real-time PCR methods for
detecting eDNA to document species distributions in natural habitats, especially
in habitats with high concentrations of PCR inhibitors.
PMID- 25850373
TI - Contributions of spinal D-amino acid oxidase to chronic morphine-induced
hyperalgesia.
AB - Spinal D-amino acid oxidase (DAAO) is an FAD-dependent peroxisomal flavoenzyme
which mediates the conversion of neutral and polar D-amino acids (including D
serine) to the corresponding alpha-keto acids, and simultaneously produces
hydrogen peroxide and ammonia. This study has aimed to explore the potential
contributions of spinal DAAO and its mediated hydrogen peroxide/D-serine
metabolism to the development of morphine-induced hyperalgesia. Bi-daily
subcutaneous injections of morphine to mice over 7 days induced thermal
hyperalgesia as measured by both the hot-plate and tail-immersion tests, and
spinal astroglial activation with increased spinal gene expression of DAAO, glial
fibrillary acidic protein (GFAP) and pro-inflammatory cytokines (interleukin
1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
alpha)). Subcutaneous injections of the potent DAAO inhibitor CBIO (5-chloro
benzo[D]isoxazol-3-ol) prevented and reversed the chronic morphine-induced
hyperalgesia. CBIO also inhibited both astrocyte activation and the expression of
pro-inflammatory cytokines. Intrathecal injection of the hydrogen peroxide
scavenger PBN (phenyl-N-tert-butylnitrone) and of catalase completely reversed
established morphine hyperalgesia, whereas subcutaneous injections of exogenous D
serine failed to alter chronic morphine-induced hyperalgesia. These results
provided evidence that spinal DAAO and its subsequent production of hydrogen
peroxide rather than the D-serine metabolism contributed to the development of
morphine-induced hyperalgesia.
PMID- 25850374
TI - A direct qPCR method for residual DNA quantification in monoclonal antibody drugs
produced in CHO cells.
AB - Chinese hamster ovary (CHO) cells are the host cell of choice for manufacturing
of monoclonal antibody (mAb) drugs in the biopharmaceutical industry. Host cell
DNA is an impurity of such manufacturing process and must be controlled and
monitored in order to ensure drug purity and safety. A conventional method for
quantification of host residual DNA in drug requires extraction of DNA from the
mAb drug substance with subsequent quantification of the extracted DNA using real
time PCR (qPCR). Here we report a method where the DNA extraction step is
eliminated prior to qPCR. In this method, which we have named 'direct resDNA
qPCR', the mAb drug substance is digested with a protease called KAPA in a 96
well PCR plate, the protease in the digest is then denatured at high temperature,
qPCR reagents are added to the resultant reaction wells in the plate along with
standards and controls in other wells of the same plate, and the plate subjected
to qPCR for analysis of residual host DNA in the samples. This direct resDNA qPCR
method for CHO is sensitive to 5.0fg of DNA with high precision and accuracy and
has a wide linear range of determination. The method has been successfully tested
with four mAbs drug, two IgG1 and two IgG4. Both the purified drug substance as
well as a number of process intermediate samples, e.g., bioreactor harvest,
Protein A column eluate and ion-exchange column eluates were tested. This method
simplifies the residual DNA quantification protocol, reduces time of analysis and
leads to increased assay sensitivity and development of automated high-throughput
methods.
PMID- 25850375
TI - Somitogenesis: From somite to skeletal muscle.
AB - Myogenesis is controlled by an elaborate system of extrinsic and intrinsic
regulatory mechanisms in all development stages. The aim of this review is to
provide an overview of the different stages of myogenesis and muscle
differentiation in mammals, starting from somitogenesis and analysis of the
different portions that constitute the mature somite. Particular attention was
paid to regulatory genes, in addition to mesodermal stem cells, which represent
the earliest elements of myogenesis. Finally, the crucial role of growth factors,
molecules of vital importance in contractile regulation, hormones and their
function in skeletal muscle differentiation, growth and metabolism, and the role
played by central nervous system, are discussed.
PMID- 25850377
TI - New Dimeric and seco-Abietane Diterpenoids from Salvia wardii.
AB - Two dimeric abietane diterpenoids, salviwardins A and B (1 and 2), and a seco
abietane diterpenoid salviwardin C (3), along with five known analogues (4-8),
were isolated from the roots of Salvia wardii. The structures of these isolates
were elucidated by extensive spectroscopic methods. The inhibitory activities of
these isolates against five human cancer cell lines in vitro were also tested.
PMID- 25850378
TI - New Diterpenes from Cultures of the Fungus Engleromyces goetzii and Their CETP
Inhibitory Activity.
AB - One new cleistanthane-type diterpene named engleromycenolic acid A (1), one new
rosane-type diterpene named engleromycenolic acid B (2) and one new natural
rosane-type diterpene, engleromycenol (3), along with three known rosane-type
diterpenes, rosololactone (4), rosenonolactone (5) and 7-deoxyrosenonolactone (6)
were isolated from cultures of the fungus Engleromyces goetzii, where it
naturally grows on Alpine bamboo culms. The new compounds were elucidated based
on their spectroscopic data. In addition, compounds 1-6 were evaluated for their
cholesterol ester transfer protein (CETP) inhibition activity. This paper reports
the isolation, structural elucidation, and CETP inhibition activity of these
compounds.
PMID- 25850380
TI - Interaction between anti-Alzheimer and antipsychotic drugs in modulating
extrapyramidal motor disorders in mice.
AB - Antipsychotics are often used in conjunction with anti-Alzheimer drugs to treat
the behavioral and psychological symptoms of dementia (BPSD). Here, we examined
the effects of cholinesterase inhibitors (ChEIs), donepezil and galantamine, on
antipsychotic-induced extrapyramidal side effects (EPS) in mice. The effects of
serotonergic agents on the EPS drug interaction were also evaluated. Donepezil
(0.3-3 mg/kg) did not induce EPS signs by itself; however, it significantly
potentiated bradykinesia induction with a low dose of haloperidol (0.5 mg/kg) in
dose-dependent and synergistic manners. Galantamine (0.3-3 mg/kg) elicited mild
bradykinesia at a high dose and dose-dependently augmented haloperidol-induced
bradykinesia. The EPS potentiation by galantamine was blocked by trihexyphenidyl
(a muscarinic antagonist), but not by mecamylamine (a nicotinic antagonist). In
addition, the bradykinesia potentiation by galantamine was significantly reduced
by (+/-)-8-hydroxy-2-(di-n-propylamino)-tetralin (a 5-HT1A agonist), ritanserin
(a 5-HT2 antagonist), and SB-258585 (a 5-HT6 antagonist). The present results
give us a caution for the antipsychotics and ChEIs interaction in inducing EPS in
the treatment of BPSD. In addition, second generation antipsychotics, which can
stimulate 5-HT1A receptors or antagonize 5-HT2 and 5-HT6 receptors, seem to be
favorable as an adjunctive therapy for BPSD.
PMID- 25850381
TI - Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass
grafts.
AB - As we previously demonstrated the role of different K(+) channels in the action
of nicorandil on human saphenous vein (HSV) and human internal mammary artery
(HIMA), this study aimed to analyse the contribution of the cGMP pathway in
nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the
K(+) channel-activating effect of nicorandil. An inhibitor of soluble guanylate
cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while
ODQ plus glibenclamide, a selective ATP-sensitive K(+) (KATP) channel inhibitor,
produced a further inhibition of both vessels. In HSV, ODQ in combination with 4
aminopyridine, a blocker of voltage-gated K(+) (KV) channels, did not modify the
concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus
iberiotoxin, a selective blocker of large-conductance Ca(2+)-activated K(+)
(BKCa) channels, produced greater inhibition than ODQ alone. We showed that the
cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on
HSV and HIMA. It seems that nicorandil directly opens KATP channels in both
vessels and BKCa channels in HIMA, although it is possible that stimulation of GC
contributes to KATP channels activation in HIMA. Contrary, the activation of KV
channels in HSV is probably due to GC activation and increased levels of cGMP.
PMID- 25850382
TI - Biochemistry students' ideas about how an enzyme interacts with a substrate.
AB - Enzyme-substrate interactions are a fundamental concept of biochemistry that is
built upon throughout multiple biochemistry courses. Central to understanding
enzyme-substrate interactions is specific knowledge of exactly how an enzyme and
substrate interact. Within this narrower topic, students must understand the
various binding sites on an enzyme and be able to reason from simplistic lock and
key or induced fit models to the more complex energetics model of transition
state theory. Learning to understand these many facets of enzyme-substrate
interactions and reasoning from multiple models present challenges where students
incorrectly make connections between concepts or make no connection at all. This
study investigated biochemistry students' understanding of enzyme-substrate
interactions through the use of clinical interviews and a national administration
(N = 707) of the Enzyme-Substrate Interactions Concept Inventory. Findings
include misconceptions regarding the nature of enzyme-substrate interactions,
naive ideas about the active site, a lack of energetically driven interactions,
and an incomplete understanding of the specificity pocket.
PMID- 25850383
TI - Effect of electroconvulsive seizures on pattern separation.
AB - Strategies employing different techniques to inhibit or stimulate neurogenesis
have implicated a role for adult-born neurons in the therapeutic effect of
antidepressant drugs, as well as a role in memory formation. Electroconvulsive
seizures (ECS), an animal model of electroconvulsive therapy, robustly stimulate
hippocampal neurogenesis, but it is not known how this relates to either
therapeutic efficacy or unwanted cognitive side effects. We hypothesized that the
ECS-derived increase in adult-born neurons would manifest in improved pattern
separation ability, a memory function that is believed to be both hippocampus
dependent and coupled to neurogenesis. To test this hypothesis, we stimulated
neurogenesis in adult rats by treating them with a series of ECS and compared
their performances in a trial-unique delayed nonmatching-to-location task (TUNL)
to a control group. TUNL performance was analyzed over a 12-week period, during
which newly formed neurons differentiate and become functionally integrated in
the hippocampal neurocircuitry. Task difficulty was manipulated by modifying the
delay between sample and choice, and by varying the spatial similarity between
target and distracter location. Although animals learned the task and improved
the number of correct responses over time, ECS did not influence spatial pattern
separation ability.
PMID- 25850385
TI - Reflections on New York City's 1947 Smallpox Vaccination Program and Its 1976
Swine Influenza Immunization Program.
AB - In 1947, a smallpox outbreak occurred in New York City with a total of twelve
cases and two deaths. In order to contain this outbreak, the New York City
Department of Health launched a mass immunization campaign that over a period of
some 60 days vaccinated 6.35 million people. This article examines in detail the
epidemiology of this outbreak and the measures employed to contain it. In 1976, a
swine influenza strain was isolated among a few recruits at a US Army training
camp at Fort Dix, New Jersey. It was concluded at the time that this virus
possibly represented a re-appearance of the 1918 influenza pandemic influenza
strain. As a result, a mass national immunization program was launched by the
federal government. From its inception, the program encountered a myriad of
challenges ranging from doubts that it was even necessary to the development of
Guillain-Barre paralysis among some vaccine recipients. This paper examines the
planning for and implementation of the swine flu immunization program in New York
City. It also compares it to the smallpox vaccination program of 1947. Despite
equivalent financial and personnel resources, leadership and organizational
skills, the 1976 program only immunized approximately a tenth of the number of
New York City residents vaccinated in 1947. The reasons for these marked
differences in outcomes are discussed in detail.
PMID- 25850386
TI - A Randomized Trial to Compare Alternative Educational Interventions to Increase
Colorectal Cancer Screening in a Hard-to-Reach Urban Minority Population with
Health Insurance.
AB - This randomized controlled trial assessed different educational approaches for
increasing colorectal cancer screening uptake in a sample of primarily non-US
born urban minority individuals, over aged 50, with health insurance, and out of
compliance with screening guidelines. In one group, participants were mailed
printed educational material (n = 180); in a second, participants' primary care
physicians received academic detailing to improve screening referral and follow
up practices (n = 185); in a third, physicians received academic detailing and
participants received tailored telephone education (n = 199). Overall, 21.5% of
participants (n = 121) received appropriate screening within one year of
randomization. There were no statistically significant pairwise differences
between groups in screening rate. Among those 60 years of age or older, however,
the detailing plus telephone education group had a higher screening rate than the
print group (27.3 vs. 7.7%, p = .02). Different kinds of interventions will be
required to increase colorectal cancer screening among the increasingly small
population segment that remains unscreened. ClinicalTrials.gov Identifier:
NCT02392143.
PMID- 25850388
TI - Complications and neurological deficits following minimally invasive anterior
column release for adult spinal deformity: a retrospective study.
AB - BACKGROUND: Minimally invasive techniques have become increasing popular and are
expanding into deformity surgery. The lateral retroperitoneal transpsoas anterior
column release (ACR) is a newer minimally invasive alternative to posterior
osteotomy techniques for correcting and promoting global spinal alignment. This
procedure attempts to avoid the potential complications associated with
conventional osteotomies, but has its own subset of unique complications to be
discussed in depth. METHODS: A retrospective review was performed in all patients
who underwent the minimally invasive (MIS) ACR procedure from 2010 to present at
our institution. All perioperative and postoperative complications were recorded
by an independent reviewer. Demographics, spinopelvic parameters, and operative
data were collected. The primary etiologic diagnosis was adult spinal deformity.
Spinopelvic parameters were measured based on standing 36-inch scoliosis films.
RESULTS: Thirty-one patients underwent a total of 47 MIS-ACRs. The mean age of
the cohort was 62. Mean follow up was 12 months (range 3-38 months). The average
change from in lumbar lordosis (LL) was 17.6 degrees , in pelvic tilt was 4.3
degrees , coronal Cobb was 13.9 and in SVA was 3.8 cm. Of the 47 MIS-ACR
procedures, there were 9 (9/47, 19 %) major complications related to the ACR.
Iliopsoas weakness was seen in eight patients and retrograde ejaculation in one
patient. Only one patient remained with mild motor deficit at the most recent
follow-up. No revision surgeries were required for the anterolateral approach.
There was no vascular, visceral, or infectious complications associated with the
MIS-ACR. CONCLUSION: The MIS-ACR is one of the most technically demanding
procedures performed from the lateral transpsoas approach. This procedure has the
advantage of maintaining and improving spinal global alignment while minimizing
blood loss and excessive tissue dissection. It comes with its own unique set of
potentially catastrophic complications and should only be performed by surgeons
proficient in both deformity correction and the lateral approach.
PMID- 25850387
TI - MIS lateral spine surgery: a systematic literature review of complications,
outcomes, and economics.
AB - BACKGROUND: Over the past decade, the minimally disruptive lateral transpsoas
approach for lumbar interbody fusion (MI-LIF) is increasingly being used as an
alternative to conventional surgical approaches. The purpose of this review was
to evaluate four primary questions as they relate to MI-LIF: (1) Is there an
anatomical justification for MI-LIF at L4-5? (2) What are the complication and
outcome profiles of MI-LIF and are they acceptable with respect to conventional
approaches? (3) Given technical and neuromonitoring differences between various
MI-LIF procedures, are there any published clinical differences? And, (4) are
modern minimally disruptive procedures (e.g., MI-LIF) economically viable?
METHODS: Through a MEDLINE and Google Scholar search, a total of 237 articles
that discussed MI-LIF were identified. Of those, topical areas included anatomy
(22), biomechanics/testing (17), technical descriptions (11), case reports (40),
complications (30), clinical and radiographic outcomes (43), deformity (23),
trauma or thoracic applications (10), and review articles (41). RESULTS: In
answer to the questions posed, (1) there is a high strength of evidence showing
MI-LIF to be anatomically justified at all levels of the lumbar spine from L1-2
to L4-5. The evidence also supports the use of advanced neuromonitoring
modalities. (2) There is moderate strength evidence in support of reproducible
and reasonable complication, side effect, and outcome profiles following MI-LIF
which may be technique dependent. (3) There is low-strength evidence that shows
elevated neural complication rates in non-traditional (e.g., shallow-docking
approaches and/or those without specialized neuromonitoring) MI-LIF, and (4)
there is low- to moderate-strength evidence that modern minimally disruptive
surgical approaches are cost-effective. CONCLUSIONS: There is considerable
published evidence to support MI-LIF in spinal fusion and advanced applications,
though the results of some reports, especially concerning complications, vary
greatly depending on technique and instrumentation used. Additional cost
effectiveness analyses would assist in fully understanding the long-term
implications of MI-LIF.
PMID- 25850390
TI - Anterior cervical interbody fusion with the Zero-P spacer: mid-term results of
two-level fusion.
AB - PURPOSE: Our aim was to compare the safety and efficacy of anterior cervical
discectomy and fusion (ACDF) using the Zero-P spacer versus the plate method in
patients with cervical spine spondylosis. METHODS: Clinical and radiologic data
from 69 patients undergoing two-level ACDF from January 2009 to May 2011 were
collected prospectively. The Zero-P spacer was implanted in 37 patients (group A)
and the anterior cervical plate and interbody cage in 32 (group B). Patients were
followed for at least 3 years after surgery. Clinical outcomes were analyzed
using the Neck Disability Index and Japanese Orthopaedic Association (JOA)
scoring. The thickness of the prevertebral soft tissue at the fused levels was
measured on the lateral cervical spine radiographs and dysphagia was assessed
using the Bazaz score. Fusion rate, change in cervical lordosis, and adjacent
segment degeneration were analyzed. RESULTS: Neurologic outcomes were
statistically equivalent between the two groups. The incidence of postoperative
dysphagia was significantly lower in group A than in group B at 2 and 6 months (p
< 0.05). At the final follow-up, there were no significant differences in the C2
C7 Cobb angles between the two groups (p > 0.05). Also, degenerative changes in
adjacent segments occurred in five group A patients and seven group B patients (p
= 0.361). There were no differences in fusion rate during the radiologic follow
up. CONCLUSIONS: Clinical results with the Zero-P spacer used for two-level ACDF
were satisfactory. The device is superior to the traditional plate for preventing
postoperative dysphagia and avoiding possible complications associated with a
plate. Prospective trials with more patients and longer follow-ups are required
to confirm these observations.
PMID- 25850391
TI - Risk factors for predicting cement leakage following percutaneous vertebroplasty
for osteoporotic vertebral compression fractures.
AB - PURPOSE: The purpose of the present study is to identify independent risk factors
for the occurrence of cement leakage (CL) during percutaneous vertebroplasty
(PVP) for four different leakage types in treating osteoporotic vertebral
compression fractures (OVCFs). METHODS: We retrospectively reviewed 292 patients
who underwent PVP for single-level OVCF from January 2009 to March 2011. The
influences of several potential risk factors that might affect the occurrence of
CL were assessed using univariate and multivariate analyses. Cement leakage was
evaluated by computed tomography and classified into four different types:
through the basivertebral vein (B-type), the segmental vein (S-type), a cortical
defect (C-type), and intradiscal leakage (D-type). RESULTS: Cement leakage was
found in 227 of the 292 treated vertebrae. None of the parameters showed a
statistically significant effect by univariate analysis. However, multivariate
analysis showed that cement viscosity was an independent risk factor in B-type
CL, fracture severity and fracture type were in S-type CL, fracture severity and
presence of cleft on MRI were in C-type CL, and fracture severity, cortical
disruption on MRI, presence of cleft on MRI and cement viscosity were in D-type
CL. CONCLUSION: Each different vertebral fracture pattern has its own risk
factors for CL. Identification of the above predicting factors for CL
preoperatively might be helpful for more rigorous and strict patient selection
criteria for the appropriate candidates for PVP.
PMID- 25850392
TI - Intervertebral disc degenerative changes after intradiscal injection of TNF-alpha
in a porcine model.
AB - PURPOSE: To investigate whether exogenous tumor necrosis factor-alpha (TNF-alpha)
will initiate a degenerative process in intervertebral disc in vivo. METHODS:
Exogenous TNF-alpha in dosages of 50 and 100 ng in 50 MUL Dulbecco's Modified
Essential Medium (DMEM) was injected into porcine lumbar discs; a third disc was
injected only with 50 MUL DMEM as a control. Magnetic resonance imaging (MRI)
yielding T1- and T2-weighted images, T2-mapping, and post-contrast T1 images was
performed and histology was studied as well. RESULTS: After 3 months, a
significant decrease in T2 value calculated from T2-mapping MRI was observed in
the annulus and nucleus of both groups injected with TNF-alpha along with a
slight decrease in disc height and nucleus volumes in comparison to the control
discs. No obvious visual differences among the groups were observed in the normal
T1- and T2-weighted MRI images. Post-contrast T1 MRI showed increased annulus
enhancement in both TNF-alpha-injected groups compared to the control discs,
while no enhancement difference was observed in the nucleus. Histological
analysis showed degenerative changes with annulus fissure, cell cluster, nucleus
matrix loss, vascularization and interleukin-1beta expression in the outer
annulus of both TNF-alpha-injected discs, while no degenerative changes were
observed in the control discs. CONCLUSIONS: Intradiscal injection of exogenous
TNF-alpha caused early stage disc degeneration in a porcine model. It may thus
support the hypothesis of exogenic TNF-alpha being an important early
pathogenetic factor in disc degeneration.
PMID- 25850394
TI - Review of supplemental views and stress radiography in musculoskeletal trauma:
upper extremity.
AB - The standard radiographic series is not always sufficient to diagnose and
characterize subtle musculoskeletal injuries. Missed or delayed diagnoses can
negatively affect patient acute morbidity and long-term outcomes. Similarly,
management based on erroneous diagnoses may lead to unnecessary treatment and
restrictions. Body part or joint specific supplemental radiographic views and
stress radiography offer an alternative for further evaluation of subtle injuries
in specific clinical situations and may obviate the need for the added cost and
potential ionizing radiation exposure of further cross-sectional imaging.
Familiarity with these complementary exams allows radiologists to play an
important role in patient care, as their utilization can improve diagnostic
accuracy, clarify subtle or uncertain findings, and direct timely patient
management. This review highlights important supplemental views and stress
radiographic examinations useful in the evaluation of emergent upper extremity
musculoskeletal trauma.
PMID- 25850393
TI - Reduced expression of miRNA-1237-3p associated with poor survival of spinal
chordoma patients.
AB - PURPOSE: Aberrant expression of miRNAs has been demonstrated to contribute to
human carcinogenesis. This study was aimed at profiling differentially expressed
miRNAs in formalin-fixed and paraffin-embedded tissues of spinal chordoma and
testing the potential for using altered expression of miRNAs as prognostic
markers for spinal chordoma patients. METHODS: A miRNA array was used to profile
differentially expressed miRNAs in spinal chordoma and nucleus pulposus tissues.
Four of these differentially expressed miRNAs was then validated in spinal
chordoma and control patients using quantitative RT-PCR. Bioinformatical analysis
identified potential GO terms and signaling pathways affected by these microRNAs.
Altered miR-1237-3p expression was then found to be associated with
clinicopathological characteristics and prognosis of spinal chordoma patients.
RESULTS: The miRNA arrays identified 29 differentially expressed miRNAs in spinal
chordoma tissues, four of which were verified by qRT-PCR in 42 spinal chordomas
and 14 control tissues. Bioinformatical analysis revealed that the potential
target genes of these miRNAs were mainly involved in gene transcription, cell
junction proteins, and gene pathways in cancer and endocytosis. Reduced miR-1237
3p expression was associated with tumor invasion and worse recurrence-free
survival of spinal chordoma patients (chi (2) = 16.217, p = 0.000, log-rank
test). Multivariate analyses showed that miR-1237-3p expression was an
independent prognostic factor for patients with spinal chordoma (HR = 0.001, 95 %
CI 0.000-0.136, p = 0.005). CONCLUSION: The data from the current study
identified a total of 29 differentially expressed miRNAs in chordoma tissues and
reduced miR-1237-3p expression was associated with chordoma invasion and worse
recurrence-free survival of the patients.
PMID- 25850395
TI - Predicting the potential distribution of the amphibian pathogen Batrachochytrium
dendrobatidis in East and Southeast Asia.
AB - Batrachochytrium dendrobatidis (Bd) is the pathogen responsible for
chytridiomycosis, a disease that is associated with a worldwide amphibian
population decline. In this study, we predicted the potential distribution of Bd
in East and Southeast Asia based on limited occurrence data. Our goal was to
design an effective survey area where efforts to detect the pathogen can be
focused. We generated ecological niche models using the maximum-entropy approach,
with alleviation of multicollinearity and spatial autocorrelation. We applied
eigenvector-based spatial filters as independent variables, in addition to
environmental variables, to resolve spatial autocorrelation, and compared the
model's accuracy and the degree of spatial autocorrelation with those of a model
estimated using only environmental variables. We were able to identify areas of
high suitability for Bd with accuracy. Among the environmental variables, factors
related to temperature and precipitation were more effective in predicting the
potential distribution of Bd than factors related to land use and cover type. Our
study successfully predicted the potential distribution of Bd in East and
Southeast Asia. This information should now be used to prioritize survey areas
and generate a surveillance program to detect the pathogen.
PMID- 25850396
TI - Evaluation of emamectin benzoate and substance EX against salmon lice in sea
ranched Atlantic salmon smolts.
AB - Experimental releases of Atlantic salmon smolts treated with emamectin benzoate
(EB) against salmon lice have previously been used to estimate the significance
of salmon lice on the survival of migrating smolts. In recent years, the salmon
louse has developed reduced sensitivity to EB, which may influence the results of
such release experiments. We therefore tested the use of 2 anti-lice drugs: EB
was administered to salmon smolts in high doses by intra-peritoneal injection and
the prophylactic substance EX (SubEX) was administered by bathing. A third,
untreated control group was also established. Salmon were challenged with
copepodids of 2 strains of salmon lice (1 EB-sensitive strain and 1 with reduced
EB-sensitivity) in mixed-group experimental tanks. At 31 d post-challenge, the
numbers of pre-adult lice on treated fish were around 20% compared with the
control fish, with minor or no differences between the 2 treatments and lice
strains. Both treatments therefore appeared to give the smolts a high degree of
protection against infestation of copepodids of salmon lice. However,
significantly lower growth of the EB-treatment group indicates that bathing the
fish in SubEX is less stressful for smolts than intra-peritoneal injection of EB.
PMID- 25850397
TI - Molecular and morphological evidence for the widespread distribution of Laticola
paralatesi infecting wild and farmed Lates calcarifer in Australia.
AB - Infections with monogeneans of the Diplectanidae can limit productivity of and
cause considerable health issues for fish in aquaculture. To date, 9 species of
diplectanids have been reported from the Asian sea bass or barramundi Lates
calcarifer (Perciformes: Latidae) in the Asia-Pacific region. This study
characterised the diplectanid parasite fauna found infecting wild and farmed
barramundi from 5 localities in tropical Australia, including north Queensland
and Western Australia. A combination of morphometric and comparative genetic
analyses of partial 28S ribosomal RNA (28S rRNA) from specimens recovered were
used to confirm their identity and to explore relationships with other
diplectanids. These data revealed that a single, dominant species of diplectanid,
Laticola paralatesi, infects wild and farmed Lates calcarifer in tropical
Australia. Laticola lingaoensis Yang, Kritsky, Sun, Jiangying, Shi & Agrawal,
2006 is synonymised with L. seabassi (Wu, Li, Zhu & Xie, 2005) Domingues &
Boeger, 2008 based on the combination of the host infected (Lates calcarifer),
geographic distribution, distinct morphological similarity, and identical 28S
rRNA sequence data identified here. Laticola seabassi is now designated as the
type species of Laticola due to nomenclatural priority.
PMID- 25850398
TI - Growth inhibition of Aeromonas salmonicida and Yersinia ruckeri by disinfectants
containing peracetic acid.
AB - Peracetic acid (PAA) is a therapeutic agent used for disinfection in aquaculture,
but it must be investigated thoroughly in order to mitigate diseases without
harming the fish. Successful disinfectants (like PAA) should not leave dangerous
residues in the environment in order to successfully contribute to sustainable
aquaculture. The aim of our study was to compare the effectiveness of 6
commercial PAA products with different molecular PAA:H2O2 ratios to reduce
bacterial growth of Aeromonas salmonicida and Yersinia ruckeri and to determine
effective concentrations and exposure times. All products reduced colony-forming
units (CFUs) of A. salmonicida and Y. ruckeri. Products with higher molecular
PAA:H2O2 ratios inhibited growth better than products with lower molecular
PAA:H2O2 ratios at the same PAA concentration; this indicates that H2O2 is not
the driving force in the reduction of A. salmonicida and Y. ruckeri growth by PAA
in vitro. The practical application of the products with high molecular PAA:H2O2
ratios should be prioritized if these pathogens are diagnosed.
PMID- 25850399
TI - Monoclonal antibody against a putative myristoylated membrane protein encoded by
grouper iridovirus 59L gene.
AB - Groupers (Epinephelus spp.) are economically important fish species worldwide,
and ranaviruses are major viral pathogens causing heavy economic losses in
grouper aquaculture. In this study, the 59L gene of grouper iridovirus (GIV-59L)
was cloned and characterized. This gene is 1521 bp and encodes a protein of 506
amino acids with a predicted molecular mass of 53.9 kDa. Interestingly, GIV-59L
and its homologs are found in all genera of the family Iridoviridae. A mouse
monoclonal antibody specific for the C-terminal domain (amino acid positions 254
506) of the GIV-59L protein, GIV-59L(760-1518)-MAb-21, was produced and proved to
be well suited for use in a number of GIV immunoassays. RT-PCR, Western blotting,
and cycloheximide and cytosine arabinoside drug inhibition analyses indicated
that GIV-59L is a viral late gene in GIV-infected grouper kidney cells.
Immunofluorescence analysis revealed that GIV-59L protein mainly accumulates in
the cytoplasm of infected cells and is finally packed into a whole virus
particle. The GIV-59L(760-1518)-MAb-21 characterized in this study could have
widespread application in GIV immunodiagnostics and other research on GIV. In
addition, the results presented here offer important insights into the
pathogenesis of GIV.
PMID- 25850400
TI - Histopathological effects of atrazine on gills of Caspian kutum Rutilus frisii
kutum fingerlings.
AB - The use of chemical pesticides has increased environmental pollution and affects
fishes as non-target organisms. To investigate the toxic effects of the widely
used herbicide atrazine on Caspian kutum Rutilus frisii kutum fingerlings, fish
were exposed to a sublethal concentration of half LC50 for 96 h. The main
alterations visible in the gill tissue were detachment of the epithelium of the
lamellae, necrosis, lamellar fusion, hyperplasia, club shaped lamellae, collapse
of the lamellae, shrinkage and curling of the lamellae, and ultrastructural
alterations such as necrosis of the apical microridges of the pavement cells.
Results also showed that the gill ionocytes were fewer in number and larger in
size in the atrazine-exposed fish. Atrazine appears to be highly toxic to Caspian
kutum fingerlings even at a sublethal concentration (12.47 mg l(-1)) and acute
exposure. This toxicity could affect gill respiration and ion regulation function
of fingerlings by damaging tissue, pavement cells, and ionocytes.
PMID- 25850401
TI - Temperature correlates with annual changes in Hematodinium perezi prevalence in
blue crab Callinectes sapidus in Florida, USA.
AB - Blue crabs Callinectes sapidus were monitored biannually throughout Florida, USA,
for 2 yr using a highly sensitive, quantitative polymerase chain reaction (qPCR)
to determine the spatial and temporal changes in prevalence and intensity of
Hematodinium perezi infections during drought years. Despite persistent drought
conditions, H. perezi infections were not universally found. Overall prevalence
was 25.3% (95% CI: 22.8-28.1%) in 1066 crabs sampled from 6 locations
(Jacksonville, Ormond Beach, Everglades City, Tampa Bay, Steinhatchee, and Panama
City) from 2011 to 2012. Presence of H. perezi was consistently highest in winter
season samples, ranging from 4.2-51.1% (3 locations) in 2011, to 32-83% (5
locations) in 2012. The highest prevalence and intensities were observed in the
winter samples from Everglades City. Previous studies have found that the
prevalence of H. perezi in C. sapidus in temperate regions of the US East Coast
shows seasonal peaks in early winter in Maryland and South Carolina and in fall
and spring in Georgia. The seasonality of infections in the subtropical waters of
Florida reinforces the concept that temperature is a strong factor that may
override other drivers, such as drought. Seasonal H. perezi infections in Florida
appear to be triggered by the parasite responding to an optimal temperature
during the annual rise from the low temperature of winter when salinity is
elevated. However, salinity alone is not sufficient to trigger an increase in
prevalence of H. perezi in Florida.
PMID- 25850402
TI - Cell proteome variability of protistan mollusc parasite Perkinsus olseni among
regions of the Spanish coast.
AB - We evaluated the proteome variability of in vitro-cultured Perkinsus olseni cells
deriving from 4 regions of the Spanish coast: the rias of Arousa and Pontevedra
(Galicia, NW Spain), Carreras River in Huelva (Andalusia, SW Spain) and Delta de
l'Ebre (Catalonia, NE Spain). P. olseni in vitro clonal cultures were produced
starting from parasite isolates from 4 individual clams from each region. Those
clonal cultures were used to extract cell proteins, which were separated by 2
dimensional (2D) electrophoresis. Qualitative comparison of P. olseni protein
expression profiles among regions was performed with PD Quest software. Around
700 protein spots from parasites derived from each region were considered, from
which 141 spots were shared by all the regions. Various spots were found to be
exclusive to each region. Higher similarity was found among the proteomes of P.
olseni from the Atlantic regions than between those from the Mediterranean and
the Atlantic. A total of 54 spots were excised from the gels and sequenced.
Nineteen proteins were annotated after searching in databases, 13 being shared by
all the regions and 6 exclusive to 1 region. Most of the identified proteins were
involved in glycolysis, oxidation/reduction, metabolism and response to stress.
No direct evidence of P. olseni variability associated with virulence was found
within the protein set analysed, although the differences in metabolic adaptation
and stress response could be connected to pathogenicity.
PMID- 25850403
TI - Phaeohyphomycosis resulting in obstructive tracheitis in three green sea turtles
Chelonia mydas stranded along the Florida coast.
AB - Three wild immature green sea turtles Chelonia mydas were found alive but
lethargic on the shores of the Indian River Lagoon and Gulf of Mexico in Florida,
USA, and subsequently died. Necropsy findings in all 3 turtles included partial
occlusion of the trachea by a mass comprised of granulomatous inflammation.
Pigmented fungal hyphae were observed within the lesion by histology and were
characterized by culture and sequencing of the internal transcribed spacer 2
domain of the rRNA gene and D1/D2 region of the fungal 28s gene. The dematiaceous
fungus species Veronaea botryosa was isolated from the tracheal mass in 2 cases,
and genetic sequence of V. botryosa was detected by polymerase chain reaction in
all 3 cases. Genetic sequencing and fungal cultures also detected other
dematiaceous fungi, including a Cladosporium sp., an Ochroconis sp., and a
Cochliobolus sp. These cases are the first report of phaeohyphomycosis caused by
V. botryosa in wild marine animals.
PMID- 25850404
TI - Petromyzon marinus (Petromyzontidae), an unusual host for helminth parasites in
western Europe.
AB - The sea lamprey Petromyzon marinus, which is among the most phylogenetically
ancient vertebrates, is a hematophagous ectoparasite that feeds on vertebrates
and is considered vulnerable in Europe but is a pest in the North American Great
Lakes. We conducted a literature review of helminth parasites of P. marinus and
investigated postmetamorphic lampreys sampled in rivers and northeast Atlantic
coastal waters (western France) during spawning migration. Based on the
literature review, 16 helminth taxa have been recorded in P. marinus, among them
14 in North America but only 2 in Europe, with no species in common between these
areas. Specific parasites are lacking, and helminth parasites recorded in P.
marinus are mostly opportunistic and are trophically transmitted to fish hosts
with both extremely low prevalence and mean intensity. Thus, P. marinus seems an
unusual host that is probably infected through accidental ingestion of parasites
by microphagous larvae (ammocoetes) and/or hematophagous postmetamorphs. Our
field study supports this hypothesis, since only a single third-stage larva of
Anisakis simplex sensu stricto was found in 2 postmetamorphic P. marinus among
the 115 individuals dissected. This opportunistic, trophically transmitted, and
cosmopolitan nematode species has never been recorded in North American sea
lampreys and only once in Galician rivers (southern Europe). Infestation pathways
of P. marinus by A. simplex are proposed vis-a-vis the feeding strategy of
postmetamorphs and fish host species which potentially harbor anisakid larvae in
their musculature. More generally, the complexity of biotic interactions is
discussed considering P. marinus both as a host for helminth parasites and as a
parasite for hosts such as fish and mammals, which are also potential predators
of sea lamprey.
PMID- 25850405
TI - Altered visual feedback modulates cortical excitability in a mirror-box-like
paradigm.
AB - Watching self-generated unilateral hand movements reflected in a mirror-oriented
along the midsagittal plane-enhances the excitability of the primary motor cortex
(M1) ipsilateral to the moving hand of the observer. Mechanisms detecting sensory
motor conflicts generated by the mirror reflection of such movements might
mediate this effect; if so, cortical excitability should be modulated by the
magnitude of sensory-motor conflict. To this end, we explored the modulatory
effects of an altered visual feedback on M1 excitability in a mirror-box-like
paradigm, by increasing or decreasing the speed of the observed movement. Healthy
subjects performed movements with their left index finger while watching a video
of a hand superimposed to their right static hand, which was hidden from view.
The hand observed in the video executed the same movement as the observer's left
hand, but at slower, same, or faster paces. Motor evoked potentials (MEPs)
induced by transcranial magnetic stimulation were measured from the first dorsal
interosseous and the abductor digiti minimi of the participant's hidden resting
hand. The excitability of the M1 ipsilateral to the moving hand was
systematically modulated by the speed of the observed hand movement: the slower
the observed movement, the greater the MEP amplitude from both muscles. This
evidence shows that the magnitude of the visual-motor conflicts can be used to
adjust the activity of the observer's motor system. Hence, an appropriate
alteration of the visual feedback, here the reduction in the movement speed, may
be useful to increase its modulatory effect on motor cortical excitability.
PMID- 25850406
TI - Unified nature of bimanual movements revealed by separating the preparation of
each arm.
AB - Movement preparation of bimanual asymmetric movements is longer than bimanual
symmetric movements in choice reaction time conditions, even when movements are
cued directly by illuminating the targets (Blinch et al. in Exp Brain Res
232(3):947-955, 2014). This bimanual asymmetric cost may be caused by increased
processing demands on response programming, but this requires further
investigation. The present experiment tested the demands on response programming
for bimanual movements by temporally separating the preparation of each arm. This
was achieved by precuing the target of one arm before the imperative stimulus. We
asked: What was prepared in advance when one arm was precued? The answer to this
question would suggest which process causes the bimanual asymmetric cost. Advance
movement preparation was examined by comparing reaction times with and without a
precue for the left target and by occasionally replacing the imperative stimulus
with a loud, startling tone (120 dB). A startle tone releases whatever movement
is prepared in advance with a much shorter reaction time than control trials
(Carlsen et al. in Clin Neurophysiol 123(1):21-33, 2012). Participants made
bimanual symmetric and asymmetric reaching movements in simple and 2-choice
reaction time conditions and a condition with a precue for the left target. We
found a bimanual asymmetric cost in 2-choice conditions, and the asymmetric cost
was significantly smaller when the left target was precued. These results, and
the results from startle trials, suggest (1) that the precued movement was not
fully programmed but partially programmed before the imperative stimulus and (2)
that the asymmetric cost was caused by increased processing demands on response
programming. Overall, the results support the notion that bimanual movements are
not the sum of two unimanual movements; instead, the two arms of a bimanual
movement are unified into a functional unit. When one target is precued, this
critical unification likely occurs during response programming.
PMID- 25850407
TI - Arm dominance affects feedforward strategy more than feedback sensitivity during
a postural task.
AB - Handedness is a feature of human motor control that is still not fully
understood. Recent work has demonstrated that the dominant and nondominant arm
each excel at different behaviors and has proposed that this behavioral asymmetry
arises from lateralization in the cerebral cortex: the dominant side specializes
in predictive trajectory control, while the nondominant side is specialized for
impedance control. Long-latency stretch reflexes are an automatic mechanism for
regulating posture and have been shown to contribute to limb impedance. To
determine whether long-latency reflexes also contribute to asymmetric motor
behavior in the upper limbs, we investigated the effect of arm dominance on
stretch reflexes during a postural task that required varying degrees of
impedance control. Our results demonstrated slightly but significantly larger
reflex responses in the biarticular muscles of the nondominant arm, as would be
consistent with increased impedance control. These differences were attributed
solely to higher levels of voluntary background activity in the nondominant
biarticular muscles, indicating that feedforward strategies for postural
stability may differ between arms. Reflex sensitivity, which was defined as the
magnitude of the reflex response for matched levels of background activity, was
not significantly different between arms for a broad subject population ranging
from 23 to 51 years of age. These results indicate that inter-arm differences in
feedforward strategies are more influential during posture than differences in
feedback sensitivity, in a broad subject population. Interestingly, restricting
our analysis to subjects under 40 years of age revealed a small increase in long
latency reflex sensitivity in the nondominant arm relative to the dominant arm.
Though our subject numbers were small for this secondary analysis, it suggests
that further studies may be required to assess the influence of reflex
lateralization throughout development.
PMID- 25850408
TI - Resveratrol inhibits inflammation and ameliorates insulin resistant endothelial
dysfunction via regulation of AMP-activated protein kinase and sirtuin 1
activities.
AB - BACKGROUND: Resveratrol is a phytoalexin with beneficial effects on human health.
The aim of the present study was to investigate the effects of resveratrol on
endothelial dysfunction involved in insulin signaling and inflammation. METHODS:
Endothelial cells were stimulated with palmitate (PA) to induce insulin
resistance characterized by a loss of insulin-mediated nitric oxide (NO)
production. Diabetes was induced in rats by fructose feeding. The effects of
resveratrol and the mechanisms involved were investigated using an aortic
relaxation assay and Western blot analysis. RESULTS: In endothelial cells, 0.1-10
MUmol/L resveratrol suppressed IkappaB kinase beta (IKKbeta)/nuclear factor
kappaB phosphorylation, as well as tumor necrosis factor-alpha and interleukin-6
production, and restored the insulin receptor substrate-1 (Irs-1)/Akt/endothelial
NO synthase signaling pathway. Furthermore, resveratrol effectively inhibited the
mitogenic actions of insulin by decreasing the secretion of endothelin-1 and
plasminogen activator inhibitor-1. It also positively regulated AMP-activated
kinase (AMPK) and sirtuin 1 (SIRT1) activation, which contributed to the
inhibition of inflammation implicated in endothelial insulin resistance.
Stimulation with PA and long term-fructose feeding impaired insulin-mediated
vessel dilation in rat aorta, whereas pretreatment of aortic rings with
resveratrol (0.1-10 MUmol/L) or treatment of rats with 5 or 20 mg/kg resveratrol
counteracted these changes. CONCLUSION: The results indicate that resveratrol
inhibits inflammation and facilitates insulin phosphatidylinositol 3-kinase
signaling by beneficial modulation of IRS-1 function partly via regulation of
AMPK and SIRT1 activity in the endothelium.
PMID- 25850409
TI - Identification of receptor-type protein tyrosine phosphatase MU as a new marker
for osteocytes.
AB - Osteocytes are the predominant cells in bone, where they form a cellular network
and display important functions in bone homeostasis, phosphate metabolism and
mechanical transduction. Several proteins strongly expressed by osteocytes are
involved in these processes, e.g., sclerostin, DMP-1, PHEX, FGF23 and MEPE, while
others are upregulated during differentiation of osteoblasts into osteocytes,
e.g., osteocalcin and E11. The receptor-type protein tyrosine phosphatase u
(RPTPMU) has been described to be expressed in cells which display a cellular
network, e.g., endothelial and neuronal cells, and is implied in
mechanotransduction. In a capillary outgrowth assay using metatarsals derived
from RPTPMU-knock-out/LacZ knock-in mice, we observed that the capillary
structures grown out of the metatarsals were stained blue, as expected.
Surprisingly, cells within the metatarsal bone tissue were positive for LacZ
activity as well, indicating that RPTPMU is also expressed by osteocytes.
Subsequent histochemical analysis showed that within bone, RPTPMU is expressed
exclusively in early-stage osteocytes. Analysis of bone marrow cell cultures
revealed that osteocytes are present in the nodules and an enzymatic assay
enabled the quantification of the amount of osteocytes. No apparent bone
phenotype was observed when tibiae of RPTPMU-knock-out/LacZ knock-in mice were
analyzed by MUCT at several time points during aging, although a significant
reduction in cortical bone was observed in RPTPMU-knock-out/LacZ knock-in mice at
20 weeks. Changes in trabecular bone were more subtle. Our data show that RPTPMU
is a new marker for osteocytes.
PMID- 25850410
TI - Human sperm molecular anatomy: the enzyme 5alpha-reductase (SRD5A) is present in
the sperm and may be involved in the varicocele-related infertility.
AB - The most common cause of male infertility is the testicular varicocele, a
condition that impairs production and decreases quality of sperm. Male fertility
also strictly depends on androgens acting through their own receptor. The enzyme
5alpha-reductase (SRD5A) is involved in the conversion of testosterone to 5alpha
dihydrotestosterone, both required for the development and maintenance of male
reproductive function. Here, we evaluated, by western blotting analysis, the
presence of SRD5A in human ejaculated spermatozoa and evidenced differences in
sperm SRD5A content between healthy donors and varicocele-affected patients.
Additionally, SRD5A sperm ultrastructural localization was also assessed by
transmission electron microscopy and immunogold assay. We evidenced that SRD5A
enzyme is present in the human spermatozoa and that its cellular content is
lowered in sperm samples from varicocele patients compared to healthy subjects.
The presence of SRD5A in human ejaculated spermatozoa highlights the potential
role of this enzyme in sperm physiopathology suggesting that the decrease in its
content, by affecting the conversion of testosterone into 5alpha
dihydrotestosterone, may be an important additional mechanism involved in the
harmful effect of varicocele in male fertility.
PMID- 25850411
TI - Allan-Herndon-Dudley syndrome with unusual profound sensorineural hearing loss.
AB - The Allan-Herndon-Dudley syndrome is caused by mutations in the thyroid hormone
transporter, Monocarboxylate transporter 8 (MCT8). It is characterized by
profound intellectual disability and abnormal thyroid function. We report on a
patient with Allan-Herndon-Dudley syndrome (AHDS) with profound sensorineural
hearing loss which is not usually a feature of AHDS and which may have been due
to a coexisting nonsense mutation in Microphthalmia-associated transcription
factor (MITF).
PMID- 25850412
TI - Erratum: A vlincRNA participates in senescence maintenance by relieving H2AZ
mediated repression at the INK4 locus.
PMID- 25850414
TI - The eating disorder examination: reliability and validity of the Italian version.
AB - OBJECTIVE: To examine the psychometric characteristics of the Italian language
version of the latest edition of the eating disorder examination (EDE). METHODS:
An Italian version of the EDE (17th edition) was designed and administered to 185
in- and outpatients with eating disorders and 60 age-matched controls. Its
internal consistency, inter-rater reliability, short-term (7-23 days) test-retest
reliability and criterion validity were evaluated. RESULTS: Internal consistency
was high for all four original EDE subscales. Inter-rater reliability was
excellent for global EDE scores and original subscales (>=0.93), and for eating
disorder behaviours (>=0.89). Test-retest reliability was good for global EDE
scores and original subscales (0.57-0.80), objective bulimic episodes and days,
vomiting episodes, laxative and diuretic misuse episodes, and excessive
exercising (>=0.82), but unsatisfactory for subjective bulimic episodes and days.
Patients with eating disorders displayed significantly higher EDE scores than age
matched controls, demonstrating the good criterion validity of the instrument.
CONCLUSIONS: The Italian version of the EDE 17.0D has adequate psychometric
properties and can therefore be recommended for examining Italian patients with
eating disorders in clinical and research settings.
PMID- 25850413
TI - Enhanced recovery protocols (ERP) in robotic cystectomy surgery. Review of
current status and trends.
AB - Open radical cystectomy with pelvic lymphadenectomy and urinary diversion is
associated with a high complication rate. Robotic-assisted laparoscopic radical
cystectomy is increasingly performed in many urologic surgical departments in an
effort to reduce surgical stress and decrease perioperative morbidity. Robotic
cystectomy survival studies demonstrate similar oncologic outcomes compared to
the open procedure. Enhanced recovery protocols (ERP) after major surgery are
multimodal perioperative interventions to reduce surgical stress, complications,
and patient convalescence. Evidence for different ERP interventions are currently
mainly from colorectal surgery and recently adapted to major urologic operations
including cystectomy. Guidelines for perioperative care after open radical
cystectomy for bladder cancer were recently published, but these recommendations
may differ when considering a robotic approach. Therefore, we look at the current
evidence for ERP in both open and robotic radical cystectomy and the potential
for improving ERPs in robotic cystectomy by utilizing a totally intracorporeal
robotic cystectomy approach. We also present the Karolinska ERP currently
utilized in totally intracorporeal robotic cystectomy.
PMID- 25850415
TI - Evaluation of the sensitivity of bacterial and yeast cells to cold atmospheric
plasma jet treatments.
AB - The focus of this research was first to determine the influence of the
atmospheric plasma drive frequency on the generation of atomic oxygen species and
its correlation with the reduction of bacterial load after treatment in vitro.
The treatments were carried out using a helium-plasma jet source called
PlasmaStreamTM. The susceptibility of multiple microbial cell lines was
investigated in order to compare the response of gram-positive and gram-negative
bacteria, as well as a yeast cell line to the atmospheric plasma treatment. It
was observed for the source evaluated that at a frequency of 160 kHz, increased
levels of oxygen-laden active species (i.e., OH, NO) were generated. At this
frequency, the maximum level of bacterial inactivation in vitro was also
achieved. Ex vivo studies (using freshly excised porcine skin as a human analog)
were also carried out to verify the antibacterial effect of the plasma jet
treatment at this optimal operational frequency and to investigate the effect of
treatment duration on the reduction of bacterial load. The plasma jet treatment
was found to yield a 4 log reduction in bacterial load after 6 min of treatment,
with no observable adverse effects on the treatment surface. The gram-negative
bacterial cell lines were found to be far more susceptible to the atmospheric
plasma treatments than the gram-positive bacteria. Flow cytometric analysis of
plasma treated bacterial cells (Escherichia coli) was conducted in order to
attain a fundamental understanding of the mode of action of the treatment on
bacteria at a cellular level. This study showed that after treatment with the
plasma jet, E. coli cells progressed through the following steps of cell death;
the inactivation of transport systems, followed by depolarization of the
cytoplasmic membrane, and finally permeabilization of the cell wall.
PMID- 25850416
TI - Numerical simulation of an atmospheric pressure RF-driven plasma needle and heat
transfer to adjacent human skin using COMSOL.
AB - Plasma medicine is an emerging field where plasma physics is used for
therapeutical applications. Temperature is an important factor to take into
account with respect to the applications of plasma to biological systems. During
the treatment, the tissue temperature could increase to critical values. In this
work, a model is presented, which is capable of predicting the skin temperature
during a treatment with a radio frequency driven plasma needle. The main gas was
helium. To achieve this, a discharge model was coupled to a heat transfer and
fluid flow model. The results provide maximum application times for different
power depositions in order to avoid reaching critical skin temperatures.
PMID- 25850417
TI - Ocular oncology in India.
PMID- 25850418
TI - What doctors have in common with architects--part 1: a manual art.
PMID- 25850419
TI - Toxicological and Genotoxicity Assessment of a Dihydroquercetin-Rich Dahurian
Larch Tree (Larix gmelinii Rupr) Extract (Lavitol).
AB - Safety assessment is reported of an orally ingested dihydroquercetin-rich extract
(Lavitol) derived from the Dahurian larch tree, used as a food additive and as a
dietary supplement ingredient. Dihydroquercetin, a potent antioxidant, is also
known as taxifolin. The results of genotoxicity and toxicological tests (Comet
assay, micronucleus test in human lymphocytes, chromosomal aberration test,
subacute 7-day oral toxicity study, subchronic 90-day toxicology study with
histopathologies, and, prenatal and postnatal developmental toxicity studies) on
the extract provide further support for the safety of its consumption as a food
supplement and food additive.
PMID- 25850420
TI - Controlled in vivo swimming of a swarm of bacteria-like microrobotic flagella.
AB - In vivo imaging and actuation of a swarm of magnetic helical microswimmers by
external magnetic fields (less than 10 mT) in deep tissue is demonstrated for the
first time. This constitutes a major milestone in the field, yielding a
generation of micrometer-scale transporters with numerous applications in
biomedicine including synthetic biology, assisted fertilization, and drug/gene
delivery.
PMID- 25850421
TI - Engineering protein folding and translocation improves heterologous protein
secretion in Saccharomyces cerevisiae.
AB - Saccharomyces cerevisiae is widely used as a producer of heterologous proteins of
medical and industrial interest. Numerous efforts have been made to overcome
bottlenecks in protein expression and secretion. However, the effect of
engineering protein translocation to heterologous protein secretion has not been
studied extensively in S. cerevisiae. In this work, we confirmed that
heterologous protein expression in S. cerevisiae induced the unfolded protein
response (UPR). To enhance protein folding capacity, the endoplasmic reticulum
(ER) chaperone protein BiP and the disulfide isomerase Pdi1p were each over
expressed, and the secretion of three heterologous proteins, beta-glucosidase,
endoglucanase, and alpha-amylase, was improved. The impact of engineering key
translocation components was also studied. The over-expression of co
translational translocation components Srp14p and Srp54p enhanced the secretion
of three heterologous proteins (beta-glucosidase, endoglucanase, and alpha
amylase), but over-expressing the cytosolic chaperone Ssa1p (involved in post
translational translocation) only enhanced the secretion of beta-glucosidase. By
engineering both co-translational translocation and protein folding, we obtained
strains with beta-glucosidase, endoglucanase, and alpha-amylase activities
increased by 72%, 60%, and 103% compared to the controls. Our results show that
protein translocation may be a limiting factor for heterologous protein
production.
PMID- 25850422
TI - Two novel sodium channel mutations associated with resistance to indoxacarb and
metaflumizone in the diamondback moth, Plutella xylostella.
AB - Indoxacarb and metaflumizone belong to a relatively new class of sodium channel
blocker insecticides (SCBIs). Due to intensive use of indoxacarb, field-evolved
indoxacarb resistance has been reported in several lepidopteran pests, including
the diamondback moth Plutella xylostella, a serious pest of cruciferous crops. In
particular, the BY12 population of P. xylostella, collected from Baiyun,
Guangdong Province of China in 2012, was 750-fold more resistant to indoxacarb
and 70-fold more resistant to metaflumizone compared with the susceptible Roth
strain. Comparison of complementary DNA sequences encoding the sodium channel
genes of Roth and BY12 revealed two point mutations (F1845Y and V1848I) in the
sixth segment of domain IV of the PxNav protein in the BY population. Both
mutations are located within a highly conserved sequence region that is predicted
to be involved in the binding sites of local anesthetics and SCBIs based on
mammalian sodium channels. A significant correlation was observed among 10 field
collected populations between the mutant allele (Y1845 or I1848) frequencies
(1.7% to 52.5%) and resistance levels to both indoxacarb (34- to 870-fold) and
metaflumizone (1- to 70-fold). The two mutations were never found to co-exist in
the same allele of PxNav , suggesting that they arose independently. This is the
first time that sodium channel mutations have been associated with high levels of
resistance to SCBIs. F1845Y and V1848I are molecular markers for resistance
monitoring in the diamondback moth and possibly other insect pest species.
PMID- 25850423
TI - Isolation and full-genome sequence of two reticuloendotheliosis virus strains
from mixed infections with Marek's disease virus in China.
AB - Reticuloendotheliosis virus (REV), classified as a gammaretrovirus, has a variety
of hosts, including chickens, ducks, geese, turkeys, and wild birds. REV causes a
series of pathological syndromes, especially the immunosuppression of the host,
which may lead to an increased susceptibility to other pathogens, thus greatly
damaging the poultry industry. Mixed infections of REV and Marek's disease virus
(MDV) have been reported in many countries, including China. Previous reports
revealed that MDV vaccines were not efficacious, and even less-virulent MDV
strains would cause some losses due to mixed infections with REV. Additionally,
contaminants in the MDV vaccine might be the main source of REV. In this study,
two clinical samples were collected from two flocks of chickens that were
diagnosed with MDV. Subsequently, two REV isolates were obtained from the
clinical samples. The isolates, named CY1111 and SY1209, were further confirmed
through an indirect immunofluorescence assay and electron microscopy. Complete
genome sequences of the two REV strains were determined to test the relationship
between them and other REV strains. Phylogenetic trees showed that the two REV
strains were closely related to most REV strains that were isolated from a
variety of hosts. Therefore, REVs might spread freely among these hosts under
natural conditions. Additionally, most REV strains in China were in the same
clade. The present work offers some information regarding REV in China.
PMID- 25850424
TI - Spatial analysis of gastroschisis in the National Birth Defects Prevention Study.
AB - BACKGROUND: Gastroschisis is a birth defect where loops of bowel are protruding
from the abdominal wall at birth. Previous research has suggested that
gastroschisis cases can occur in clusters. The objective of this study was to
identify if there were areas of elevated gastroschisis risk using data from the
National Birth Defects Prevention Study (NBDPS), 1997 through 2007. METHODS: We
obtained data on cases (n = 371) through population-based birth defects
surveillance systems in Arkansas, California, and Utah; controls (n = 2359) were
selected from the same geographic areas as cases. Mothers were interviewed on
demographic information and exposures during pregnancy, including residential
history. We used first trimester maternal addresses and generalized additive
models to create a continuous map surface of odds ratios (OR) by smoothing over
latitude and longitude. Permutation tests were used to assess whether location of
maternal residence was important and identify locations with statistically
significant ORs. RESULTS: In Arkansas, adjusted ORs in the southwest corner were
2.0 and the global deviance was not statistically significant (p-value: 0.57).
Adjusted ORs for California indicated areas of increased risk with ORs 1.3 (p
value: 0.34). In Utah, the adjusted ORs were elevated (OR: 2.4) in the south
eastern corner of the study area (p-value: 0.34). CONCLUSION: The results of this
study, while not statistically significant, suggest there were spatial variations
in gastroschisis births. We cannot rule out that these variations were due to
edge effects or residual confounding.
PMID- 25850426
TI - X Chromosome and Autosome Dosage Responses in Drosophila melanogaster Heads.
AB - X chromosome dosage compensation is required for male viability in Drosophila.
Dosage compensation relative to autosomes is two-fold, but this is likely to be
due to a combination of homeostatic gene-by-gene regulation and chromosome-wide
regulation. We have baseline values for gene-by-gene dosage compensation on
autosomes, but not for the X chromosome. Given the evolutionary history of sex
chromosomes, these baseline values could differ. We used a series of deficiencies
on the X and autosomes, along with mutations in the sex-determination gene
transformer-2, to carefully measure the sex-independent X-chromosome response to
gene dosage in adult heads by RNA sequencing. We observed modest and
indistinguishable dosage compensation for both X chromosome and autosome genes,
suggesting that the X chromosome is neither inherently more robust nor sensitive
to dosage change.
PMID- 25850428
TI - Mood instability as a precursor to depressive illness: A prospective and
mediational analysis.
AB - OBJECTIVE: Mood instability levels are high in depression, but temporal
precedence and potential mechanisms are unknown. Hypotheses tested were as
follows: (1) mood instability is associated with depression cross-sectionally,
(2) mood instability predicts new onset and maintenance of depression
prospectively and (3) the mood instability and depression link are mediated by
sleep problems, alcohol abuse and life events. METHOD: Data from the National
Psychiatric Morbidity Survey 2000 at baseline (N = 8580) and 18-month follow-up
(N = 2413) were used. Regression modeling controlling for socio-demographic
factors, anxiety and hypomanic mood was conducted. Multiple mediational analyses
were used to test our conceptual path model. RESULTS: Mood instability was
associated with depression cross-sectionally (odds ratio: 5.28; 95% confidence
interval: [3.67, 7.59]; p < 0.001) and predicted depression inception (odds
ratio: 2.43; 95% confidence interval: [1.03-5.76]; p = 0.042) after controlling
for important confounders. Mood instability did not predict maintenance of
depression. Sleep difficulties and severe problems with close friends and family
significantly mediated the link between mood instability and new onset depression
(23.05% and 6.19% of the link, respectively). Alcohol abuse and divorce were not
important mediators in the model. CONCLUSION: Mood instability is a precursor of
a depressive episode, predicting its onset. Difficulties in sleep are a
significant part of the pathway. Interventions targeting mood instability and
sleep problems have the potential to reduce the risk of depression.
PMID- 25850427
TI - Insights into Ongoing Evolution of the Hexachlorocyclohexane Catabolic Pathway
from Comparative Genomics of Ten Sphingomonadaceae Strains.
AB - Hexachlorocyclohexane (HCH), a synthetic organochloride, was first used as a
broad-acre insecticide in the 1940s, and many HCH-degrading bacterial strains
have been isolated from around the globe during the last 20 years. To date, the
same degradation pathway (the lin pathway) has been implicated in all strains
characterized, although the pathway has only been characterized intensively in
two strains and for only a single HCH isomer. To further elucidate the evolution
of the lin pathway, we have biochemically and genetically characterized three HCH
degrading strains from the Czech Republic and compared the genomes of these and
seven other HCH-degrading bacterial strains. The three new strains each yielded a
distinct set of metabolites during their degradation of HCH isomers. Variable
assembly of the pathway is a common feature across the 10 genomes, eight of which
(including all three Czech strains) were either missing key lin genes or
containing duplicate copies of upstream lin genes (linA-F). The analysis also
confirmed the important role of horizontal transfer mediated by insertion
sequence IS6100 in the acquisition of the pathway, with a stronger association of
IS6100 to the lin genes in the new strains. In one strain, a linA variant was
identified that likely caused a novel degradation phenotype involving a shift in
isomer preference. This study identifies a number of strains that are in the
early stages of lin pathway acquisition and shows that the state of the pathway
can explain the degradation patterns observed.
PMID- 25850429
TI - Bevacizumab in recurrent glioblastoma: five informative patient scenarios.
AB - Glioblastoma is the most common and malignant primary brain tumour in adults.
Maximum feasible surgical resection, radiotherapy and temozolomide chemotherapy
at initial diagnosis have improved prognosis but rapid recurrence is typical and
survival remains brief. There is an urgent need for effective new treatments and
approval of the antiangiogenic agent bevacizumab for recurrent glioblastoma by
Health Canada in 2009 has been the most notable recent therapeutic advance for
this disease. This review with illustrative case studies highlights how
bevacizumab has been incorporated into the treatment of glioblastoma in Canada
and describes the ongoing controversies surrounding its clinical application.
PMID- 25850430
TI - Assessing impairment of executive function and psychomotor speed in premanifest
and manifest Huntington's disease gene-expansion carriers.
AB - Executive functions (EF) and psychomotor speed (PMS) has been widely studied in
Huntington's disease (HD). Most studies have focused on finding markers of
disease progression by comparing group means at different disease stages. Our aim
was to investigate performances on nine measures of EF and PMS in a group of
premanifest and manifest HD-gene expansion carriers and to investigate which
measures were most sensitive for assessment of individual patients by analyzing
frequencies of impaired performances relative to healthy controls. We recruited
HD gene-expansion carriers, 48 manifest and 50 premanifest and as controls 39
healthy gene-expansion negative individuals. All participants underwent
neurological examination and neuropsychological testing with nine cognitive
measures. The frequency of impairment was investigated using cutoff scores. In
group comparisons the manifest HD gene-expansion carriers scored significantly
worse than controls on all tests and in classification of individual scores the
majority of scores were classified as probably impaired (10th percentile) or
impaired (5th percentile) with Symbol Digit Modalities Test (SDMT) being the most
frequently impaired. Group comparisons of premanifest HD gene-expansion carriers
and healthy controls showed significant differences on SDMT and Alternating
fluency tests. Nevertheless the frequencies of probably impaired and impaired
scores on individual tests were markedly higher for Alternating and Lexical
fluency tests than for SDMT. We found distinct group differences in frequency of
impairment on measures of EF and PMS in manifest and premanifest HD gene
expansion carriers. Our results indicate to what degree these measures can be
expected to be clinically impaired.
PMID- 25850431
TI - [Transcripts from automated external defibrillator are important].
AB - We report a case where a 16-year-old girl with diabetes who suffered aborted
cardiac arrest. Out of hospital the patient received a shock from an automated
external defibrillator (AED) due to ventricular fibrillation (VF). Neither the VF
nor the shock were reported to the receiving hospital. After referral to another
hospital the AED transcript was read and the patient received an implantable
cardioverter-defibrillator. Transcripts from AEDs used in the resuscitation of
patients with cardiac arrest should always be analysed in order to optimize the
diagnostic process and secure correct treatment.
PMID- 25850432
TI - The silkworm GSTe4 is sensitive to phoxim and protects HEK293 cells against UV
induced cell apoptosis.
AB - Glutathione S-transferases (GSTs, EC 2.5.1.18) are a family of super enzymes with
multiple functions that play a major role in the detoxification of endogenous and
xenobiotic compounds. In our previous study, we have predicted 23 putative
cytosolic GSTs in the silkworm genome using bioinformatic methods. In this study,
we cloned and studied the insect-specific epsilon-class GST gene GSTe4 from the
silkworm, Bombyx mori. The recombinant BmGSTe4 (Bac-BmGSTe4) was overexpressed in
SF-9 cell lines, and it was found to have effective GST activity. We also found
that the expression of BmGSTe4 was especially down-regulated after the silkworms
were fumigated with or ingested phoxim. Moreover, BmGSTe4 protected HEK293 cells
against UV-induced cell apoptosis. These results demonstrated that BmGSTe4 has
GST activity, is sensitive to phoxim, and plays a role in inhibition of UV
induced cell apoptosis.
PMID- 25850433
TI - Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and
Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative
Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting
Sorafenib Resistance in Liver Cancer.
AB - Sorafenib has become the standard therapy for patients with advanced
hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop
acquired resistance. Therefore, it is important to identify potential biomarkers
that could predict the efficacy of sorafenib. To identify target proteins
associated with the development of sorafenib resistance, we applied stable
isotope labelling with amino acids in cell culture (SILAC)-based quantitative
proteomic approach to analyze differences in protein expression levels between
parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7(R)) cells in vitro,
combined with an isobaric tags for relative and absolute quantitation (iTRAQ)
quantitative analysis of HuH-7 and HuH-7(R) tumors in vivo. In total, 2,450
quantified proteins were identified in common in SILAC and iTRAQ experiments,
with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75
showing decreased expression (<0.5-fold). In silico analyses of these
differentially expressed proteins predicted that 10 proteins were related to
cancer with involvements in cell adhesion, migration, and invasion. Knockdown of
one of these candidate proteins, galectin-1, decreased cell proliferation and
metastasis in HuH-7(R) cells and restored sensitivity to sorafenib. We verified
galectin-1 as a predictive marker of sorafenib resistance and a downstream target
of the AKT/mTOR/HIF-1alpha signaling pathway. In addition, increased galectin-1
expression in HCC patients' serum was associated with poor tumor control and low
response rate. We also found that a high serum galectin-1 level was an
independent factor associated with poor progression-free survival and overall
survival. In conclusion, these results suggest that galectin-1 is a possible
biomarker for predicting the response of HCC patients to treatment with
sorafenib. As such, it may assist in the stratification of HCC and help direct
personalized therapy.
PMID- 25850434
TI - Online Peptide fractionation using a multiphasic microfluidic liquid
chromatography chip improves reproducibility and detection limits for
quantitation in discovery and targeted proteomics.
AB - Comprehensive proteomic profiling of biological specimens usually requires
multidimensional chromatographic peptide fractionation prior to mass
spectrometry. However, this approach can suffer from poor reproducibility because
of the lack of standardization and automation of the entire workflow, thus
compromising performance of quantitative proteomic investigations. To address
these variables we developed an online peptide fractionation system comprising a
multiphasic liquid chromatography (LC) chip that integrates reversed phase and
strong cation exchange chromatography upstream of the mass spectrometer (MS). We
showed superiority of this system for standardizing discovery and targeted
proteomic workflows using cancer cell lysates and nondepleted human plasma. Five
step multiphase chip LC MS/MS acquisition showed clear advantages over analyses
of unfractionated samples by identifying more peptides, consuming less sample and
often improving the lower limits of quantitation, all in highly reproducible,
automated, online configuration. We further showed that multiphase chip LC
fractionation provided a facile means to detect many N- and C-terminal peptides
(including acetylated N terminus) that are challenging to identify in complex
tryptic peptide matrices because of less favorable ionization characteristics.
Given as much as 95% of peptides were detected in only a single salt fraction
from cell lysates we exploited this high reproducibility and coupled it with
multiple reaction monitoring on a high-resolution MS instrument (MRM-HR). This
approach increased target analyte peak area and improved lower limits of
quantitation without negatively influencing variance or bias. Further, we showed
a strategy to use multiphase LC chip fractionation LC-MS/MS for ion library
generation to integrate with SWATH(TM) data-independent acquisition quantitative
workflows. All MS data are available via ProteomeXchange with identifier
PXD001464.
PMID- 25850435
TI - A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma
Cells.
AB - Inhibitors of oncogenic B-RAF(V600E) and MKK1/2 have yielded remarkable responses
in B-RAF(V600E)-positive melanoma patients. However, the efficacy of these
inhibitors is limited by the inevitable onset of resistance. Despite the fact
that these inhibitors target the same pathway, combination treatment with B
RAF(V600E) and MKK1/2 inhibitors has been shown to improve both response rates
and progression-free survival in B-RAF(V600E) melanoma patients. To provide
insight into the molecular nature of the combinatorial response, we used
quantitative mass spectrometry to characterize the inhibitor-dependent
phosphoproteome of human melanoma cells treated with the B-RAF(V600E) inhibitor
PLX4032 (vemurafenib) or the MKK1/2 inhibitor AZD6244 (selumetinib). In three
replicate experiments, we quantified changes at a total of 23,986 phosphosites on
4784 proteins. This included 1317 phosphosites that reproducibly decreased in
response to at least one inhibitor. Phosphosites that responded to both
inhibitors grouped into networks that included the nuclear pore complex, growth
factor signaling, and transcriptional regulators. Although the majority of
phosphosites were responsive to both inhibitors, we identified 16 sites that
decreased only in response to PLX4032, suggesting rare instances where oncogenic
B-RAF signaling occurs in an MKK1/2-independent manner. Only two phosphosites
were identified that appeared to be uniquely responsive to AZD6244. When cells
were treated with the combination of AZD6244 and PLX4032 at subsaturating
concentrations (30 nm), responses at nearly all phosphosites were additive. We
conclude that AZD6244 does not substantially widen the range of phosphosites
inhibited by PLX4032 and that the benefit of the drug combination is best
explained by their additive effects on suppressing ERK1/2 signaling. Comparison
of our results to another recent ERK1/2 phosphoproteomics study revealed a
surprising degree of variability in the sensitivity of phosphosites to MKK1/2
inhibitors in human cell lines, revealing unexpected cell specificity in the
molecular responses to pathway activation.
PMID- 25850436
TI - Unveiling Contacts within Macromolecular Assemblies by Solving Minimum Weight
Connectivity Inference (MWC) Problems.
AB - Consider a set of oligomers listing the subunits involved in subcomplexes of a
macromolecular assembly, obtained e.g. using native mass spectrometry or affinity
purification. Given these oligomers, connectivity inference (CI) consists of
finding the most plausible contacts between these subunits, and minimum
connectivity inference (MCI) is the variant consisting of finding a set of
contacts of smallest cardinality. MCI problems avoid speculating on the total
number of contacts but yield a subset of all contacts and do not allow exploiting
a priori information on the likelihood of individual contacts. In this context,
we present two novel algorithms, MILP-W and MILP-WB. The former solves the
minimum weight connectivity inference (MWCI), an optimization problem whose
criterion mixes the number of contacts and their likelihood. The latter uses the
former in a bootstrap fashion to improve the sensitivity and the specificity of
solution sets.Experiments on three systems (yeast exosome, yeast proteasome lid,
human eIF3), for which reference contacts are known (crystal structure, cryo
electron microscopy, cross-linking), show that our algorithms predict contacts
with high specificity and sensitivity, yielding a very significant improvement
over previous work, typically a twofold increase in sensitivity.The software
accompanying this paper is made available and should prove of ubiquitous interest
whenever connectivity inference from oligomers is faced.
PMID- 25850437
TI - Bacteria-mediated effects of antibiotics on Daphnia nutrition.
AB - In polluted environments, contaminant effects may be manifested via both direct
toxicity to the host and changes in its microbiota, affecting bacteria-host
interactions. In this context, particularly relevant is exposure to antibiotics
released into environment. We examined effects of the antibiotic trimethoprim on
microbiota of Daphnia magna and concomitant changes in the host feeding. In
daphnids exposed to 0.25 mg L(-1) trimethoprim for 24 h, the microbiota was
strongly affected, with (1) up to 21-fold decrease in 16S rRNA gene abundance and
(2) a shift from balanced communities dominated by Curvibacter, Aquabacterium,
and Limnohabitans in controls to significantly lower diversity under dominance of
Pelomonas in the exposed animals. Moreover, decreased feeding and digestion was
observed in the animals exposed to 0.25-2 mg L(-1) trimethoprim for 48 h and then
fed 14C-labeled algae. Whereas the proportion of intact algal cells in the guts
increased with increased trimethoprim concentration, ingestion and incorporation
rates as well as digestion and incorporation efficiencies decreased
significantly. Thus, antibiotics may impact nontarget species via changes in
their microbiota leading to compromised nutrition and, ultimately, growth. These
bacteria-mediated effects in nontarget organisms may not be unique for
antibiotics, but also relevant for environmental pollutants of various nature.
PMID- 25850438
TI - Evaluation of an alginate-gelatine crosslinked hydrogel for bioplotting.
AB - Using additive manufacturing to create hydrogel scaffolds which incorporate
homogeneously distributed, immobilized cells in the context of biofabrication
approaches represents an emerging and expanding field in tissue engineering.
Applying hydrogels for additive manufacturing must consider the material
processing properties as well as their influence on the immobilized cells. In
this work alginate-dialdehyde (ADA), a partially oxidized alginate, was used as a
basic material to improve the physico-chemical properties of the hydrogel for
cell immobilization. At first, the processing ability of the gel using a
bioplotter and the compatibility of the process with MG-63 osteoblast like cells
were investigated. The metabolic and mitochondrial activities increased at the
beginning of the incubation period and they balanced at a relatively high level
after 14-28 days of incubation. During this incubation period the release of
vascular endothelial growth factor-A also increased. After 28 days of incubation
the cell morphology showed a spreading morphology and cells were seen to move out
of the scaffold struts covering the whole scaffold structure. The reproducible
processing capability of alginate-gelatine (ADA-GEL) and the compatibility with
MG-63 cells were proven, thus the ADA-GEL material is highlighted as a promising
matrix for applications in biofabrication.
PMID- 25850425
TI - Quality of anticoagulation control in preventing adverse events in patients with
heart failure in sinus rhythm: Warfarin versus Aspirin in Reduced Cardiac
Ejection Fraction trial substudy.
AB - BACKGROUND: The aim of this study is to examine the relationship between time in
the therapeutic range (TTR) and clinical outcomes in heart failure patients in
sinus rhythm treated with warfarin. METHODS AND RESULTS: We used data from the
Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial to
assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke,
intracerebral hemorrhage, or death), with death alone, ischemic stroke alone,
major hemorrhage alone, and net clinical benefit (primary outcome and major
hemorrhage combined). Multivariable Cox models were used to examine how the event
risk changed with TTR and to compare the high TTR, low TTR, and aspirin-treated
patients, with TTR being treated as a time-dependent covariate. A total of 2217
patients were included in the analyses; among whom 1067 were randomized to
warfarin and 1150 were randomized to aspirin. The median (interquartile range)
follow-up duration was 3.6 (2.0-5.0) years. Mean (+/-SD) age was 61+/-11.3 years,
with 80% being men. The mean (+/-SD) TTR was 57% (+/-28.5%). Increasing TTR was
significantly associated with reduction in primary outcome (adjusted P<0.001),
death alone (adjusted P=0.001), and improved net clinical benefit (adjusted
P<0.001). A similar trend was observed for the other 2 outcomes, but significance
was not reached (adjusted P=0.082 for ischemic stroke and adjusted P=0.109 for
major hemorrhage). CONCLUSIONS: In patients with heart failure in sinus rhythm,
increasing TTR is associated with better outcome and improved net clinical
benefit. Patients in whom good quality anticoagulation can be achieved may
benefit from the use of anticoagulants. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00041938.
PMID- 25850440
TI - Short-term effects of espresso coffee on heart rate variability and blood
pressure in habitual and non-habitual coffee consumers--a randomized crossover
study.
AB - OBJECTIVE: Coffee is one of the most widely consumed beverages worldwide. Aim of
this study was to investigate short-term effects of espresso coffee on heart rate
variability (HRV), a marker of vagal activity, in healthy habitual and non
habitual coffee consumers. METHODS: Seventy-seven healthy subjects (38 habitual
and 39 non-habitual coffee consumers, 74% women, mean age 26.97 +/- 6.88 years)
took part in three laboratory sessions in a randomized order. In condition 1,
subjects consumed espresso; in condition 2, subjects consumed decaffeinated
espresso; and in condition 3, subjects consumed warm water. HRV and blood
pressure were assessed at rest before and after ingestion of the respective
beverage. RESULTS: HRV was significantly increased after consumption of
caffeinated espresso, decaffeinated espresso, or water, indicating increased
vagal activity in the course of the experiments. In the habitual coffee
consumers, the increase in vagally mediated HRV was significantly lower after
consumption of decaffeinated espresso compared to caffeinated espresso. Increases
of systolic blood pressure were only found in the non-habitual consumers.
CONCLUSION: We found no evidence for specific short-term effects of caffeinated
espresso on vagal activity in healthy subjects. Instead, consumption of
decaffeinated espresso inhibited vagal activity in habitual consumers. This may
be explained by an attempt of the organism to establish a sympathovagal
equilibrium comparable to that after caffeine consumption. In the absence of
caffeine-induced sympathetic activation, this may have been achieved by relative
vagal withdrawal.
PMID- 25850441
TI - PARENTAL AND SIBLING MIGRATION AND HIGH BLOOD PRESSURE AMONG RURAL CHILDREN IN
CHINA.
AB - This study examines the associations between parental and sibling rural-to-urban
migration and blood pressure (BP) of rural left-behind children (LBC) in rural
China. Analysis was based on the 2000, 2004, 2006 and 2009 waves of longitudinal
data from the China Health and Nutrition Survey, which is an ongoing prospective
survey covering nine provinces with an individual-level response rate of 88%.
Blood pressure levels were measured by trained examiners at three consecutive
times on the same visit and the means of three measurements were used as the
final BP values. An ordinal BP measure was then created using a recently
validated age-sex-specified distribution for Chinese children and adolescents,
distinguishing normal BP, pre-hypertension and hypertension. Random effect
modelling was performed. Different migration circumstances play different roles
in LBC's BP with mother-only and both-parent migration being particularly
detrimental and father-only and sibling-only migration either having no
association or a negative association with LBC's BP levels or odds of high BP. In
conclusion, the link between family migration and left-behind children's blood
pressure is complex, and depends on who is the person out-migrating.
PMID- 25850439
TI - Osteoporosis prescribing in long-term care: impact of a provincial knowledge
translation strategy.
AB - This study described prescribing trends before and after implementing a
provincial strategy aimed at improving osteoporosis and fracture prevention in
Ontario long-term care (LTC) homes. Data were obtained from a pharmacy provider
for 10 LTC homes in 2007 and 166 homes in 2012. We used weighted, multiple linear
regression analyses to examine facility-level changes in vitamin D, calcium, and
osteoporosis medication prescribing rates between 2007 and 2012. After five
years, the estimated increase in vitamin D, calcium, and osteoporosis medication
prescribing rates, respectively, was 38.2 per cent (95% confidence interval [CI]:
29.0, 47.3; p < .001), 4.0 per cent (95% CI: -3.9, 12.0; p = .318), and 0.2 per
cent (95% CI: -3.3, 3.7; p = .91). Although the study could not assess causality,
findings suggest that wide-scale knowledge translation activities successfully
improved vitamin D prescribing rates, although ongoing efforts are needed to
target homes with low uptake.
PMID- 25850443
TI - Fruit-related terms and images on food packages and advertisements affect
children's perceptions of foods' fruit content.
AB - OBJECTIVE: To determine whether food label information and advertisements for
foods containing no fruit cause children to have a false impression of the foods'
fruit content. DESIGN: In the food label condition, a trained researcher showed
each child sixteen different food label photographs depicting front-of-food label
packages that varied with regard to fruit content (i.e. real fruit v. sham fruit)
and label elements. In the food advertisement condition, children viewed sixteen,
30 s television food advertisements with similar fruit content and label elements
as in the food label condition. After viewing each food label and advertisement,
children responded to the question 'Did they use fruit to make this?' with
responses of yes, no or don't know. SETTING: Schools, day-care centres, after
school programmes and other community groups. SUBJECTS: Children aged 4-7 years.
RESULTS: In the food label condition, chi 2 analysis of within fruit content
variation differences indicated children (n 58; mean age 4.2 years) were
significantly more accurate in identifying real fruit foods as the label's
informational load increased and were least accurate when neither a fruit name
nor an image was on the label. Children (n 49; mean age 5.4 years) in the food
advertisement condition were more likely to identify real fruit foods when
advertisements had fruit images compared with when no image was included, while
fruit images in advertisements for sham fruit foods significantly reduced
accuracy of responses. CONCLUSIONS: Findings suggest that labels and
advertisements for sham fruit foods mislead children with regard to the food's
real fruit content.
PMID- 25850442
TI - Biologics in combination with chemotherapy for gastric cancer: is this the
answer?
AB - Gastric cancer (GC) continues to be a significant problem worldwide and is the
third leading cause of cancer death. Armamentarium to treat GC whether it is
potentially curable or metastatic (incurable) has changed little over the last
decades with only two new agents being approved (trastuzumab and ramucirumab).
Many relatively healthy patients after second-line therapy have limited and
generally ineffective options. The recent The Cancer Genome Atlas analysis has
uncovered four genotypes of GC; however, it is not sufficient to change our
treatment strategies and more work needs to be done. The popular front-line
regimen containing a platinum compound and a fluoropyrimidine is widely used for
drug development and has worked well globally. Thus, this combination appears
suitable for adding a biologic agent. The search for new classes of cytotoxics
has almost stopped, but it is clear that cytotoxic therapy continues to
contribute and it is here to stay. Biologic agents that modulate the immune
system of the host appear promising along with many other biologics that can
potentially inhibit signaling pathways that are often employed by GC cells. We
will briefly describe the efforts that have targeted EGFR, mTOR, angiogenesis and
MET pathways.
PMID- 25850445
TI - Which Counterfactuals Matter? A Response to Beck.
PMID- 25850444
TI - A novel NGR-conjugated peptide targets DNA damage responses for
radiosensitization.
AB - Radiotherapy is one of the important treatment strategies for patients with
advanced hepatocellular carcinomas. Developing novel sensitizers for radiotherapy
is a key issue due to the low intrinsic radiosensitivity of hepatocellular
carcinomas. It was reported the wild-type NBS1 inhibitory peptide (wtNIP) can
increase radiosensitivity in several cancer cell lines by abrogating ATM-NBS1
interaction and interrupting cellular DNA damage response. Here, we developed a
novel NGRconjugated peptide (NGR-sR9-wtNIP) through coupling the CNGRC angiogenic
vessel-homing peptide NGR with the wtNIP peptide. Fusion peptide was tested for
internalization, cytotoxicity in Hep3B cells and for tumor localization, and for
toxicity in nude mice bearing human hepatocellular carcinomas xenografts. The
radiosensitizing activity of NGR-sR9-wtNIP was investigated as well. We found
that NGR-sR9-wtNIP can inhibit irradiation induced NBS1 phosphorylation and
induce radiosensitization in Hep3B cells. When combined with IR, NGR-sR9-wtNIP
suppressed tumor growth obviously in xenograft mice. In addition, the fusion
peptide localized in tumor tissue specifically and barely led to any side effects
on mice. Taken together, our data strongly suggest that NGRsR9- wtNIP has
radiosensitizing potential for radiotherapy of hepatocellular carcinomas.
PMID- 25850446
TI - Enhanced Colloidal Stability of CeO2 Nanoparticles by Ferrous Ions: Adsorption,
Redox Reaction, and Surface Precipitation.
AB - Due to the toxicity of cerium oxide (CeO2) nanoparticles (NPs), a better
understanding of the redox reaction-induced surface property changes of CeO2 NPs
and their transport in natural and engineered aqueous systems is needed. This
study investigates the impact of redox reactions with ferrous ions (Fe2+) on the
colloidal stability of CeO2 NPs. We demonstrated that under anaerobic conditions,
suspended CeO2 NPs in a 3 mM FeCl2 solution at pH 4.8 were much more stable
against sedimentation than those in the absence of Fe2+. Redox reactions between
CeO2 NPs and Fe2+ lead to the formation of 6-line ferrihydrite on the CeO2
surfaces, which enhanced the colloidal stability by increasing the zeta potential
and hydrophilicity of CeO2 NPs. These redox reactions can affect the toxicity of
CeO2 NPs by increasing cerium dissolution, and by creating new Fe(III)
(hydr)oxide reactive surface layers. Thus, these findings have significant
implications for elucidating the phase transformation and transport of redox
reactive NPs in the environment.
PMID- 25850447
TI - Mesoporous Ni0.85Se Nanospheres Grown in Situ on Graphene with High Performance
in Dye-Sensitized Solar Cells.
AB - Mesoporous Ni0.85Se nanospheres grown on graphene were synthesized via the
hydrothermal approach. Because of the exceptional electron-transfer pathway of
graphene and the excellent catalytic ability of the mesoporous Ni0.85Se
nanospheres, the nanocomposites exhibited excellent electrocatalytic property as
the counter electrode (CE) of dye-sensitized solar cells. More catalytic active
sites, better charge-transfer ability and faster reaction velocity of
Ni0.85Se@RGO (RGO = reduced graphene oxide) CE led to faster and more complete
I3(-) reduction than Pt, Ni0.85Se, and RGO CEs. Furthermore, the power conversion
efficiency of Ni0.85Se@RGO CE reached 7.82%, which is higher than that of Pt CE
(7.54%). Electrochemical impedance spectra, cyclic voltammetry, and Tafel
polarization were obtained to demonstrate positive synergetic effect between
Ni0.85Se and RGO, as well as the higher catalytic activity and the better charge
transfer ability of Ni0.85Se@RGO compared with Pt CE.
PMID- 25850448
TI - [Fever with a rash caused by chronic meningococcemia].
AB - BACKGROUND: Fever with a rash is a common clinical presentation, which can be
caused by various medical conditions. CASE DESCRIPTION: A 14-year old boy
presented at the outpatient clinic with a two-week history of fever, myalgia and
purpuric skin lesions. Blood cultures showed an infection with Neisseria
meningitidis. After antibiotic treatment, his symptoms resolved promptly.
CONCLUSION: Chronic meningococcemia is a rare manifestation of meningococcal
infection and should be considered in patients with prolonged fever, purpuric
skin lesions and joint involvement.
PMID- 25850449
TI - [Unexplained neurological dysfunction in the recovery room].
AB - BACKGROUND: Unexplained neurological dysfunction, which used to be known as
conversion disorder, is rare following general anaesthesia. This phenomenon is
difficult to identify in this situation because medically induced dysfunction
(anaesthesia) turns into unexplained dysfunction. CASE DESCRIPTION: A 58-year-old
man remained unresponsive to any stimuli for longer than expected following
uncomplicated surgery under general anaesthesia, although his vital functions
were normal. It was 2 hours after the operation before a slight eyelid response
was shown. He then lay motionless in bed for several hours. Complete recovery of
spontaneous movement and motor functions took 12 hours. No explanation was found.
CONCLUSION: Unexplained neurological dysfunction can also occur following general
anaesthesia. The diagnosis is made by neurological assessment. A wait-and-see
approach is the management policy because the neurological dysfunction disappears
spontaneously.
PMID- 25850450
TI - [A man with upper abdominal pain and a pancytopenia].
AB - A 41-year-old man visited his general practitioner because of upper abdominal
pain. Physical examination revealed splenomegaly. Laboratory testing showed
pancytopenia with a striking monocytopenia with hairy cells. Immunological and
molecular analysis confirmed the diagnosis hairy cell leukemia.
PMID- 25850451
TI - [Recurrent upper respiratory tract infections during and after rituximab
therapy].
AB - Rituximab maintenance therapy is indicated for the treatment of patients with non
Hodgkin's lymphoma (NHL) who responded to induction therapy. More than 10% of
patients will develop rituximab-induced upper respiratory tract infections
(URTIs). These infections are usually mild in patients receiving first-line or
second-line treatment. Heavily pretreated patients sometimes undergo additional
rituximab maintenance therapy. We describe three female patients aged 53, 43 and
42 years who were successfully treated with rituximab maintenance therapy after
chemotherapy for three or more recurrences of NHL. These patients developed more
serious recurrent URTIs due to rituximab-induced long-term
hypogammaglobulinaemia. In one patient, serum IgG levels continued to decline for
four years after rituximab therapy. Long-term immunoglobulin substitution was
needed to treat these patients. Physicians should be aware that URTIs may develop
in heavily pretreated patients even years after rituximab maintenance therapy and
substitution with immunoglobulin may be warranted.
PMID- 25850452
TI - [A woman with a stepladder deformity of her little finger].
AB - A 41-year-old woman presented to our emergency department after she tripped over
a doorstep. Physical examination showed swelling and a stepladder deformity of
the left little finger. Radiographs confirmed dorsal dislocation in both
interphalangeal joints. Closed manual reduction under local anaesthesia restored
position and function of the finger.
PMID- 25850453
TI - [Vogt-Koyanagi-Harada syndrome].
AB - BACKGROUND: Vogt-Koyanagi-Harada syndrome is rare in the Netherlands. However, in
Asia it is one of the most common causes of panuveitis. The syndrome is
characterised by a combination of panuveitis, pleocytosis in cerebral spinal
fluid with or without neurological function loss, alopecia and depigmentation of
body hair. CASE DESCRIPTION: A 40-year-old male with no previous medical history
visited the emergency department with unexplained bilateral visual symptoms and
optic disc swelling. In addition to the latter, further tests only showed
pleocytosis in cerebral spinal fluid. In the months following the initial
presentation, vision was restored but the patient developed panuveitis, extensive
depigmentation, and loss of body hair. On further investigation, the patient
reported having a great-grandfather from Indonesia. CONCLUSION: Vogt-Koyanagi
Harada syndrome should be considered in patients of Asian descent presenting with
panuveitis, alopecia and depigmentation of body hair. Early diagnosis and
treatment can prevent permanent visual injury.
PMID- 25850454
TI - [A neonate who could not open her eye].
AB - We present a case of a female neonate who was born with a string between the
eyelids of one eye. There were no other dysmorfic features. She had an isolated
ankyloblepharon filiforme adnatum, a rare congenital malformation of the eyelid.
PMID- 25850455
TI - [Early detection of prostate cancer--recommendations after 13 years of follow-up
in the European randomised study].
AB - The recent publication of updated results from the European randomised study of
screening for prostate cancer (ERSPC) with a median 13-year follow-up confirms
significant relative and absolute reductions in prostate cancer mortality. In
spite of existing guidelines, Dutch men and professionals remain uncertain about
the use of PSA testing. The data now available will be helpful in reaching
informed decisions. In men aged 55-69 years, the relative mortality reduction
remained similar at 21%; the absolute reduction increased from 0.9 to 1.28 fewer
deaths/1000 men screened. This translates into much improved figures needing to
be invited for screening and diagnosed, at 781 and 27 (1410 and 48 in 2009). As
expected, overall mortality does not differ between the arms of the study. The
main downside of PSA-driven screening remains the diagnosis of non-life
threatening cancers (overdiagnosis) by screening, at a frequency of about 40%,
which can be reduced by use of the Prostate Cancer Risk Calculator. Current data
support the present guideline which recommends informed decision-making, taking
into account the advantages and potential damage caused by PSA testing.
PMID- 25850456
TI - [Loss of airway after tracheotomy or laryngectomy, an algorithm for practice].
AB - A 71-year-old man underwent facial reconstructive surgery and a tracheotomy after
nasal carcinoma. Several hours after surgery, accidental decannulation occurred
and the patient died because the airway could not be resecured in time. This
incident led to the implementation of an algorithm for emergency airway
management in patients with a surgical airway after tracheotomy or laryngectomy.
All such patients have an information sheet attached to their bed, together with
the appropriate algorithm. This helps staff to provide care in a standardised
manner in cases of airway emergency and prevents fixation errors or omission of
treatment options.
PMID- 25850457
TI - [The physician and the collector of diagnoses].
AB - In the course of the medical curriculum, medical students are trained to
recognise diagnoses. They classify these in their minds, together with detailed
information on laboratory and imaging tests, as collections of diagnoses. The
downside of this could be overdiagnosis. This paper describes some of the faces
of overdiagnosis. American writer and physician Abraham Verghese eloquently
describes one of these: the e-doctor looking at a computer screen to see what is
wrong with the patient, rather than starting with a thorough clinical bedside
evaluation. Other examples include the finding of small sub-segmental pulmonary
emboli by increasingly sensitive spiral CT scanning. Finally, this paper
describes a possible answer to overdiagnosis: prognostic research, notably
answering questions such as 'what additional diagnostic testing will truly
improve my patient's prognosis, given their current presentation of signs and
symptoms?'
PMID- 25850458
TI - [Gender differences in cardiac symptoms].
AB - There is an ongoing discussion as to whether there are gender differences in
symptom presentation in acute coronary syndromes (ACS). Although the burden of
coronary artery disease (CAD) and the underlying mechanisms involved in ACS
differ significantly between the genders during various stages of life,
researchers seem to persist in comparing women against the standard for male
patients. This clouds the discussion, and may be potentially harmful to women.
The female pattern of CAD, with fewer obstructive coronary lesions and relatively
more vascular dysfunction than in men, translates into a different combination of
symptoms and relatively more type II ACS. Greater knowledge of gender-sensitive
cardiology in daily practice would improve recognition and reduce poorer ACS
outcomes in women. In 2015 the www.eugenmed.eu programme will present a gender
sensitive 'Roadmap' for cardiology practitioners within the EU.
PMID- 25850459
TI - Benzo[d]imidazole Transient Receptor Potential Vanilloid 1 Antagonists for the
Treatment of Pain: Discovery of trans-2-(2-{2-[2-(4-Trifluoromethyl-phenyl)
vinyl]-1H-benzimidazol-5-yl}-phenyl)-propan-2-ol (Mavatrep).
AB - Reported herein is the design, synthesis, and pharmacologic characterization of a
class of TRPV1 antagonists constructed on a benzo[d]imidazole platform that
evolved from a biaryl amide lead. This design composes three sections: a 2
substituted 5-phenyl headgroup attached to the benzo[d]imidazole platform, which
is tethered at the two position to a phenyl tail group. Optimization of this
design led to the identification of 4 (mavatrep), comprising a trifluoromethyl
phenyl-vinyl tail. In a TRPV1 functional assay, using cells expressing
recombinant human TRPV1 channels, 4 antagonized capsaicin-induced Ca(2+) influx,
with an IC50 value of 4.6 nM. In the complete Freund's adjuvant- and carrageenan
induced thermal hypersensitivity models, 4 exhibited full efficacy, with ED80
values of 7.8 and 0.5 mg/kg, respectively, corresponding to plasma levels of
270.8 and 9.2 ng/mL, respectively. On the basis of its superior pharmacologic and
safety profile, 4 (mavatrep) was selected for clinical development for the
treatment of pain.
PMID- 25850460
TI - Migration timing and its determinants for nocturnal migratory birds during autumn
migration.
AB - 1. Migration is a common strategy used by birds that breed in seasonal
environments, and multiple environmental and biological factors determine the
timing of migration. How these factors operate in combination during autumn
migration, which is considered to be under weaker time constraints relative to
spring migration, is not clear. 2. Here, we examine the patterns and determinants
of migration timing for nocturnal migrants during autumn migration in the north
eastern USA using nocturnal reflectivity data from 12 weather surveillance radar
stations and modelled diurnal probability of occurrence for 142 species of
nocturnal migrants. We first model the capacity of seasonal atmospheric
conditions (wind and precipitation) and ecological productivity (vegetation
greenness) to predict autumn migration intensity. We then test predictions,
formulated under optimal migration theory, on how migration timing should be
related to assemblage-level estimates of body size and total migration distance
within the context of dietary guild (insectivore and omnivore) and level of
dietary plasticity during autumn migration. 3. Our results indicate seasonal
declines in ecological productivity delineate the beginning and end of peak
migration, whose intensity is best predicted by the velocity of winds at
migration altitudes. Insectivorous migrants departed earlier in the season and,
consistent with our predictions, large-bodied and long-distance insectivorous
migrants departed the earliest. Contrary to our predictions, large-bodied and
some long-distance omnivorous migrants departed later in the season, patterns
that were replicated in part by insectivorous migrants that displayed dietary
plasticity during autumn migration. 4. Our findings indicate migration timing in
the region is dictated by optimality strategies, modified based on the breadth
and flexibility of migrant's foraging diets, with declining ecological
productivity defining possible resource thresholds during which migration occurs
when winds at migration altitudes are mild. These observations provide the basis
to assess how avian migration strategies may be affected by adjustments in
seasonal patterns of atmospheric circulation and ecological productivity that may
occur under global climate change.
PMID- 25850461
TI - Targeting NAMPT for Therapeutic Intervention in Cancer and Inflammation:
Structure-Based Drug Design and Biological Screening.
AB - Nicotinamide phosphoribosyltransferase (NAMPT) is a rate limiting enzyme that
plays an important role in the synthesis of nicotinamide adenine dinucleotide
(NAD) via a salvage pathway. Along with a role in bioenergetics, NAMPT regulates
the activity of proteins such as SIRT-1 that utilize NAD as a cofactor. As NAD
metabolism is usually high in diseased conditions, it has been hypothesized and
proven that NAMPT is over expressed in various cancers and inflammatory
disorders. Inhibitors targeting NAMPT could therefore be useful in treating
disorders arising from aberrant NAMPT signalling. In this study, inhibitors
against NAMPT were designed using an energy-based pharmacophore strategy and
evaluated for efficacy in cellular assays. Besides reducing cellular pools of NAD
and NMN, NAMPT inhibitors decreased concentrations of reactive oxygen species as
well as mRNA levels of TNFalpha and IL6, thereby implicating their potential in
alleviating the inflammatory process. In addition, reduced NAD levels
corroborated with an induction of apoptosis in prostate cancer cell lines.
PMID- 25850462
TI - Can blood pressure be lowered safely in older adults with lacunar stroke? The
Secondary Prevention of Small Subcortical Strokes study experience.
AB - OBJECTIVES: To determine safety and tolerability of lowering blood pressure in
older adults with lacunar stroke. DESIGN: Cohort study. SETTING: The Secondary
Prevention of Small Subcortical Strokes (SPS3) Trial, which compared the efficacy
of two systolic blood pressure (SBP) targets (<130 mmHg and 130-149 mmHg) for
secondary stroke prevention. PARTICIPANTS: Of 3,020 SPS3 participants, 494 aged
75 and older at baseline were used in these analyses. MEASUREMENTS: Rates of side
effects related to lowering SBP and clinical outcomes, including stroke
recurrence and vascular death, were examined. RESULTS: Older participants
achieved SBP levels similar to those of younger participants (mean SBP of 125
mmHg and 137 mmHg in lower and higher SBP target groups, respectively). At least
once during the approximately 3.5 years of follow-up, 21% reported dizziness, and
15% reported lightheadedness when standing; the only significant difference
between the younger and older groups was unsteadiness when standing (23% vs 32%
respectively, P < .001). There was no difference according to treatment group. In
younger adults, recurrent stroke was less likely in the lower than the higher SBP
group (hazard ratio (HR) = 0.77, 95% confidence interval (CI) = 0.59-1.01) but
not in older participants (HR = 1.01, 95% CI = 0.59-1.73), although the
interaction was not significant (P = .39). The lower SBP target was associated
with a significant reduction in vascular death in older participants (HR = 0.42,
95% CI = 0.18-0.98), with a significant interaction between age and SBP group (P
= .049). CONCLUSION: Except for unsteadiness when standing, there was no
difference according to age in individuals with lacunar stroke with respect to
side effects potentially related to lowering blood pressure. Although the lower
SBP target was not associated with lower likelihood of recurrent stroke, these
exploratory analyses suggested a possible benefit related to vascular death.
PMID- 25850464
TI - The Code is a chance to lobby for change.
AB - When we launched our Care campaign in 2012, one of the clear messages was: there
is no such thing as 'basic' nursing care. We took every opportunity to spread the
word among politicians and the public that ensuring a patient is clean and
comfortable and not thirsty or hungry is fundamental care. It goes to the heart
of what nursing is, and there is nothing basic about it.
PMID- 25850465
TI - Trust nurses call for help to tackle new threat to unsocial hours pay.
AB - Nurses at a large London trust are calling for a cross-union protest against
attempts to cut unsocial hours pay.
PMID- 25850463
TI - Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a
randomized controlled trial.
AB - BACKGROUND: Previous work has shown patients commonly misuse adrenaline
autoinjectors (AAI). It is unclear whether this is due to inadequate training, or
poor device design. We undertook a prospective randomized controlled trial to
evaluate ability to administer adrenaline using different AAI devices. METHODS:
We allocated mothers of food-allergic children prescribed an AAI for the first
time to Anapen or EpiPen using a computer-generated randomization list, with
optimal training according to manufacturer's instructions. After one year,
participants were randomly allocated a new device (EpiPen, Anapen, new EpiPen,
JEXT or Auvi-Q), without device-specific training. We assessed ability to deliver
adrenaline using their AAI in a simulated anaphylaxis scenario six weeks and one
year after initial training, and following device switch. Primary outcome was
successful adrenaline administration at six weeks, assessed by an independent
expert. Secondary outcomes were success at one year, success after switching
device, and adverse events. RESULTS: We randomized 158 participants. At six
weeks, 30 of 71 (42%) participants allocated to Anapen and 31 of 73 (43%)
participants allocated to EpiPen were successful - RR 1.00 (95% CI 0.68-1.46).
Success rates at one year were also similar, but digital injection was more
common at one year with EpiPen (8/59, 14%) than Anapen (0/51, 0%, P = 0.007).
When switched to a new device without specific training, success rates were
higher with Auvi-Q (26/28, 93%) than other devices (39/80, 49%; P < 0.001).
CONCLUSIONS: AAI device design is a major determinant of successful adrenaline
administration. Success rates were low with several devices, but were high using
the audio-prompt device Auvi-Q.
PMID- 25850466
TI - Student awarded for outstanding care.
AB - A 27-year-old nursing student was recognised for her care and compassion at a
prestigious awards ceremony in London attended by HRH The Princess Royal last
week.
PMID- 25850467
TI - Doctor's compassion campaign gathers momentum.
AB - A campaign begun by a terminally ill doctor to encourage healthcare professionals
to show more compassion to patients is to go on tour.
PMID- 25850468
TI - Record care clearly, accurately and with pride, RCN urges nurses.
AB - A leading nurse has urged nurses not to view record keeping as 'a chore' but
rather an integral part of providing compassionate care.
PMID- 25850469
TI - Nurses sceptical about two-week discharge target.
AB - Most nurses in Scotland do not believe the country's new two-week patient
discharge target will help reduce delays, a survey has found.
PMID- 25850470
TI - Court ruling reinforces importance of explaining treatment risks clearly.
AB - Nurses will need to ensure patients understand the seriousness of their condition
and the risks associated with proposed treatment as a result of a judgement by
the UK Supreme Court.
PMID- 25850471
TI - Pay rise would address staff shortfall in London.
AB - A good salary is a significant factor for nurses and they tend to migrate to
better salaried jobs when choices are available, according to research published
by the Institute for Fiscal Studies (IFS).
PMID- 25850472
TI - Wards' accolades for end of life care.
AB - Two NHS trusts have become the first to be recognised for the quality of their
end of life care.
PMID- 25850473
TI - Success of Dutch district nursing hard to repeat in UK.
AB - The UK healthcare system can learn from an innovative nurse-led care service in
the Netherlands, but using it here could prove a challenge because of
revalidation, the RCN said.
PMID- 25850475
TI - Staff learn the art of handling difficult conversations.
AB - Nurses in north east England have been learning how best to broach potentially
difficult conversations with patients as part of a continuing professional
development programme.
PMID- 25850476
TI - Cut agency staff and use money to train nurses, says think tank.
AB - Boosting nurse training places would save the NHS millions of pounds and improve
patient safety, a leading think tank has said.
PMID- 25850477
TI - Unions put the financial pressures facing nurses in the spotlight.
AB - NHS employers should contribute to the Nursing and Midwifery Council registration
fee as nurses continue to feel the pinch, the union Unite plans to tell the NHS
Pay Review Body.
PMID- 25850483
TI - Safe use of medicines.
AB - Essential facts In England, about 15 million people have a long-term condition -
a figure that is likely to grow with the ageing population. According to the
Health Survey for England report, published in December 2014, half of women and
43% of men in England now regularly take prescription drugs, with statins,
analgesics and antidepressants among the most common. Many long-term conditions
are managed with medicines, but it is estimated that 30-50% of prescribed
medication is not taken as intended.
PMID- 25850484
TI - 'It's rare that a prisoner has one problem'.
PMID- 25850486
TI - Spiritual solace without religion.
PMID- 25850485
TI - Ensuring we get the fundamentals right.
PMID- 25850494
TI - Sugarscience.
AB - Sugarscience was developed by health scientists from the University of California
to provide an authoritative, evidence-based resource about sugar and its effects
on health.
PMID- 25850497
TI - NHS quit smoking.
AB - NHS Quit Smoking is the official app for the NHS Smokefree campaign. It is
designed to be a companion app for the first 28 days of giving up smoking, and
uses motivational messages, progress timelines and financial calculations to
encourage quitters.
PMID- 25850498
TI - The best of the week's health-related TV and radio.
PMID- 25850499
TI - A chance to give people with learning disabilities a voice.
AB - The green paper unveiled last week by care minister Norman Lamb is a first step
to legally entitling people with learning disabilities to comment on, or even
challenge, their care.
PMID- 25850500
TI - Evidence shows high-calibre nurses are an investment in safety.
AB - James Smith is critical of June Clark's argument for mandatory nurse-patient
ratios (letters March 25), citing a single study published in the Journal of
Advanced Nursing. The study by Schreuders et al found no consistent association
between nurse staffing levels and a variety of complications in Western
Australian hospitals.
PMID- 25850501
TI - Revalidation is a great idea, but what resources will support it?
AB - I welcome revalidation and love the film at rcni.com/workplace/revalidation ,
which I have shared with my colleagues.
PMID- 25850502
TI - The money spent on revalidation could have been put to better use.
AB - I qualified as a nurse in 1983 and have continuously developed my skills and
knowledge. I have a yearly performance review with my line manager, for which I
am required to provide evidence of my practice development.
PMID- 25850503
TI - Financial pressures should not force students out of nursing.
AB - I was pleased to hear of the petition by nursing student Katherine Webb calling
on the health secretary to increase the bursary for nursing students (News April
1).
PMID- 25850507
TI - Experiences of military nurses in Iraq and Afghanistan.
AB - Since 2001 military nurses have successfully supported military operations in
deployed field hospitals in both Iraq and Afghanistan. These deployments have
presented unique challenges for military nurses. This article reviews the
literature on the experience of nurses during these deployments and, using a
thematic analysis approach, aims to understand their experience. The results
provide an insight into the lives of military nurses who served in Iraq and
Afghanistan and highlight some of the coping strategies adopted by nurses in
conflict situations. The discussion outlines the key themes and, using excerpts
from the literature, explores the challenges and coping strategies used.
PMID- 25850508
TI - Mixed methods research.
AB - Mixed methods research involves the use of qualitative and quantitative data in a
single research project. It represents an alternative methodological approach,
combining qualitative and quantitative research approaches, which enables nurse
researchers to explore complex phenomena in detail. This article provides a
practical overview of mixed methods research and its application in nursing, to
guide the novice researcher considering a mixed methods research project.
PMID- 25850509
TI - Prevention and management of constipation in adults.
AB - Constipation is a common, often chronic, condition that is a health concern for
providers of care. The condition can be distressing and although seldom life
threatening can lead to patient discomfort and debilitating effects on patients'
quality of life. Initial management of chronic constipation should include
lifestyle changes and increased fibre and fluids. More active interventions
include the use of laxatives and other medications, irrigation and biofeedback
therapy. Some patients may require surgery. This article provides an overview of
the strategies used to prevent constipation in adults as well as the possible
treatment options available.
PMID- 25850510
TI - Fluoride.
AB - A recent conversation with a colleague prompted me to read this CPD article on
fluoride. She told me my tea drinking might have health benefits in the form of
increased fluoride intake.
PMID- 25850511
TI - A passion for research.
AB - My decision to be a research student arose from my desire to add something new to
the body of knowledge about the experiences of older people from black and
minority ethnic (BME) backgrounds in hospital.
PMID- 25850512
TI - Notice board.
AB - Courses, events, grants, and awards to progress your career.
PMID- 25850513
TI - Making an objective assessment.
AB - Personal independence payments (PIP) replaced disability living allowance from
April 2013, with companies Capita and Atos carrying out assessments in England
and Wales on behalf of the Department of Work and Pensions (DWP). Nurses play a
key role in PIP assessments.
PMID- 25850514
TI - Inspection and improvement.
AB - The mention of Care Quality Commission (CQC) inspections can strike anxiety into
healthcare staff, but CQC national professional adviser Rona McCandlish says that
the CQC is about 'assisting and supporting quality improvement'.
PMID- 25850515
TI - Student life - ask us what we think.
AB - Students are in the best position to recognise the qualities of effective nurse
educators. With this in mind, we asked students on the Bachelor of Science in
Nursing (BScN) course what makes a good teacher in the clinical practice setting.
PMID- 25850516
TI - Functional analysis of truncated forms of ETV6.
PMID- 25850517
TI - Neutrophil activation by Candida glabrata but not Candida albicans promotes
fungal uptake by monocytes.
AB - Candida albicans and Candida glabrata account for the majority of candidiasis
cases worldwide. Although both species are in the same genus, they differ in key
virulence attributes. Within this work, live cell imaging was used to examine the
dynamics of neutrophil activation after confrontation with either C. albicans or
C. glabrata. Analyses revealed higher phagocytosis rates of C. albicans than C.
glabrata that resulted in stronger PMN (polymorphonuclear cells) activation by C.
albicans. Furthermore, we observed differences in the secretion of chemokines,
indicating chemotactic differences in PMN signalling towards recruitment of
further immune cells upon confrontation with Candida spp. Supernatants from co
incubations of neutrophils with C. glabrata primarily attracted monocytes and
increased the phagocytosis of C. glabrata by monocytes. In contrast, PMN
activation by C. albicans resulted in recruitment of more neutrophils. Two
complex infection models confirmed distinct targeting of immune cell populations
by the two Candida spp.: In a human whole blood infection model, C. glabrata was
more effectively taken up by monocytes than C. albicans and histopathological
analyses of murine model infections confirmed primarily monocytic infiltrates in
C. glabrata kidney infection in contrast to PMN-dominated infiltrates in C.
albicans infection. Taken together, our data demonstrate that the human
opportunistic fungi C. albicans and C. glabrata are differentially recognized by
neutrophils and one outcome of this differential recognition is the preferential
uptake of C. glabrata by monocytes.
PMID- 25850518
TI - The lived experience of fathers of preterm infants in the Neonatal Intensive Care
Unit: a systematic review of qualitative studies.
AB - AIMS AND OBJECTIVES: To systematically review the experience of fathers of
preterm infants hospitalised in the Neonatal Intensive Care Unit. BACKGROUND:
Family-centred care is more and more acknowledged in Neonatal Intensive Care
Units, advocating for active engagement of both parents in the care journey.
Nonetheless, fathers' Neonatal Intensive Care Unit experience has received
limited research attention. DESIGN: Systematic review of qualitative studies.
METHODS: Four electronic databases (CINHAL, ISI Web of Science, PubMed, Scopus)
were explored and studies published between 2000-2014 were included. Preferred
Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) and Joanna
Briggs Institute (JBI) Critical Appraisal Tool for Qualitative Studies guidelines
were adopted. Key themes were extracted and synthesised. RESULTS: Five main
themes resuming fathers' experience of preterm birth and Neonatal Intensive Care
Unit stay were identified from 14 studies. Themes were: emotional roller-coaster,
paternal needs, coping strategies, self-representation and caregiving engagement.
These dimensions were found to be dynamically shaped across three critical
turning points: preterm birth, Neonatal Intensive Care Unit stay and at home.
CONCLUSIONS: Neonatal Intensive Care Unit fathers of preterm infants experience
ambivalence, a set of different needs and coping strategies. They modify their
self-representations along the Neonatal Intensive Care Unit journey and needs
specific nursing support and intervention to sustain caregiving engagement and
transition to parenthood. RELEVANCE TO CLINICAL PRACTICE: A systematic and
deepened understanding of preterms' fathers lived experience in Neonatal
Intensive Care Unit would be helpful to inform nursing practice. Specific action
priorities are suggested within the frame of family-centred care.
PMID- 25850519
TI - Relationship between maternal pre-pregnancy body mass index, gestational weight
gain and childhood fatness at 6-7 years by air displacement plethysmography.
AB - This study aims to investigate the effect of maternal pre-pregnancy body mass
index (BMI) and gestational weight gain (GWG) on offspring body composition. In
this prospective cohort study, offspring body composition at 6 years of age was
obtained through air displacement plethysmography. Linear regression was used to
obtain crude and adjusted coefficients. Information regarding offspring body
composition and maternal pre-pregnancy BMI was available for 3156 children and on
offspring body composition and GWG for 3129 children. There was a direct
association of maternal pre-pregnancy BMI and GWG with offspring's fat mass (FM),
fat-free mass (FFM), fat mass index (FMI), fat-free mass index (FFMI) and body
fat percent (BF%) in crude and adjusted analyses. After adjustment for co
variables, for each kg m(-2) of maternal pre-pregnancy BMI increase, there was a
mean increment of 0.13 kg in the offspring FFM, 0.06 kg m(-2) in FFMI, 0.11 kg in
FM, 0.07 kg m(-2) in FMI and 0.18% in BF%. For each kilogram of maternal GWG
increase, there was a mean increment of 0.08 kg in offspring's FM, 0.05 kg m(-2)
in FMI, 0.04 kg in FFM, 0.01 kg m(-2) in FFMI and 0.18 % in BF%. Mothers with a
higher pre-pregnancy BMI or GWG tend to have children with greater adiposity at
age 6 years. Fetal overnutrition is more likely among mothers with greater BMI
during pregnancy; as a consequence, it can accelerate the childhood obesity
epidemic.
PMID- 25850520
TI - Time to surgery for hip fracture patients in a rural orthopaedic referral
hospital.
AB - PROBLEM: It is well established that shorter surgical waiting time for hip
fracture patients improves outcomes. We identify and quantify time to surgery for
hip fracture patients in a rural hospital. DESIGN: Retrospective observational
study. SETTING: : A sixty-bed rural referral hospital with an orthopaedic
service. Data were collected for 57 patients 50 years and older who had surgery
for Muller AO type 31-A and 31-B fractures at Bega Hospital in 2012. KEY MEASURES
FOR IMPROVEMENT: Time to surgery from presentation was compared for patients who
presented directly to Bega hospital to those that were transferred from a
peripheral hospital. STRATEGIES FOR CHANGE: To quantify contributing factors to
surgical delay will help identify areas for future improvement. EFFECTS OF
CHANGE: Delay to surgery from presentation was significantly greater for
transferred patients (58 hours), compared with direct presentations (41 hours).
Mean time for patient transfer was 23 hours. Thirty-five per cent of patients had
their operation within 36 hours from presentation. LESSONS LEARNT: The time to
surgery for most transfer and direct presentation patients fell outside current
guidelines. In our geographically large referral network, delay to surgery was
significantly influenced by time to transfer. Based on previously published
research, surgery for our hip fracture patients should be expedited. We therefore
recommend priority transfer for these significantly injured patients and
dedicated emergency operating lists to perform this surgery in a timely manner.
PMID- 25850521
TI - Prevalence of diabetes mellitus and prediabetes in the adult Romanian population:
PREDATORR study.
AB - BACKGROUND: The PREDATORR (PREvalence of DiAbeTes mellitus, prediabetes,
overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in
Romania) study is the first national study analyzing the prevalence of diabetes
mellitus (DM) and prediabetes, and their association with cardiometabolic,
sociodemographic, and lifestyle risk factors in the Romanian population aged 20
79 years. METHODS: This was an epidemiological study with a stratified, cross
sectional, cluster random sampling design. Sociodemographic, lifestyle, and
anamnestic data were collected through self- and interviewer-administered
questionnaires, and biochemical assays and oral glucose tolerance tests were
performed. RESULTS: In all, 2728 participants from 101 clinics of general
practitioners were randomly selected, with a probability proportional to
population size according to the 2002 Romanian Census. The participation rate was
99.6%. Impaired glucose regulation (prediabetes, known and unknown DM) was found
in 28.1% of the study population. The overall age- and sex-adjusted prevalence of
DM was 11.6% (95% CI 9.6%-13.6%), of which 2.4% (95% CI 1.7%-3.1%) had unknown
DM. The prevalence of DM increased with age and was higher in men than in women.
The age- and sex-adjusted prevalence of prediabetes was 16.5% (95%CI 14.8%
18.2%), with the highest percentage in the 60-79 year age group and in women.
Obesity, abdominal obesity, dyslipidemia, low education level, and a family
history of diabetes were associated with glucose metabolism disorders.
CONCLUSIONS: The PREDATORR study shows a high prevalence of impaired glucose
regulation in the adult Romanian population, providing data on the prevalence of
DM and prediabetes and their association with several risk factors.
PMID- 25850522
TI - Intracerebral hemorrhage at young age: long-term prognosis.
AB - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disorder
associated with dismal outcomes. The long-term mortality and functional outcome
of ICH in young patients was studied - areas so far poorly investigated. METHODS:
A follow-up study was performed on a cohort of patients. Clinical and imaging
data on ICH patients aged 16-49 were retrospectively obtained and linked with a
nationwide cause-of-death register. The modified Rankin Scale (mRS) was evaluated
for 30-day survivors at a visit 9.7 (7.0-12.0) years after ICH onset. Independent
factors associated with mortality and unfavorable functional outcome (mRS 2-5)
were sought by multivariate analysis. RESULTS: Amongst the 268 1-month survivors,
1-year survival was 98.1% [95% confidence interval (CI) 96.2%-100%], 5-year
survival 93.2% (89.3%-97.1%) and 10-year survival 88.8% (84.9%-92.7%). After
adjustment for age and intraventricular hematoma extension, male sex [odds ratio
(OR) 3.36, 95% CI 1.28-8.80] and diabetes (OR 2.64, 1.01-6.89) were associated
with increased mortality. Unfavorable functional outcome emerged in 49%. After
adjustment for confounders, age (OR 1.09 per 1 year, 95% CI 1.03-1.15), initial
stroke severity (1.17 per one National Institutes of Health Stroke Scale score
point, 1.08-1.27) and intraventricular hemorrhage (3.26, 1.11-9.55) were
associated with unfavorable functional outcome. CONCLUSIONS: Of every 10
survivors of acute phase ICH at a young age, one died within 10 years after
onset, male sex and diabetes being associated with increased mortality. Half the
survivors did not achieve a favorable functional outcome, which was predicted by
increasing age, initial stroke severity and intraventricular hemorrhage.
PMID- 25850523
TI - Concurrent Cardioversion of Atrial Fibrillation during ICD Shock Testing.
AB - BACKGROUND: Many patients receiving an implantable cardioverter-defibrillator
(ICD) also have atrial fibrillation (AF). Shock testing during ICD implantation
carries a potential risk of cardioversion to sinus rhythm (SR) and thrombembolic
events. We aimed to analyze the recurrence of AF after cardioversion to SR during
ICD shock testing. METHODS: A total of 555 consecutive patients referred to a
tertiary hospital in Switzerland for ICD implantation or generator exchange
between 02/2002 and 03/2010 were screened for AF. Fifty-seven patients who were
in AF at the time of ICD shock testing were included. RESULTS: Forty-four
patients (77%) were successfully cardioverted from AF to SR. Type of AF
(persistent, not permanent 64 vs 31% of cardioverted patients) was the only
predictor. Thirty-nine patients (89%) experienced a recurrence of AF/atrial
flutter after a median of 54 days (interquartile range 35-251 days). The only
predictor for recurrence of AF was previous AF declared as permanent. No ischemic
stroke occurred during hospitalization for the procedure. CONCLUSIONS: For
patients in AF undergoing shock testing at the time of ICD implant, there is a
high chance of cardioversion from AF to SR, but there is also a high risk of
early recurrence. Decisions regarding long-term anticoagulation should not be
based on the heart rhythm immediately following shock testing.
PMID- 25850524
TI - Positive and negative bioimprinted polymeric substrates: new platforms for cell
culture.
AB - Bioimprinting, which involves capturing cell morphological details into a polymer
matrix, provides a new class of patterned surfaces which opens an opportunity to
investigate how cells respond to their own signatures and may introduce
possibilities for regulating their behaviour. In this study, phenotypic details
of human nasal chondrocytes (HNCs) were replicated in soft polydimethylsiloxane
(PDMS) mould resulting in inverse replicas of cells, which have been termed here
as 'negative bioimprint'. For the first time, the information from this negative
bioimprint was then transferred into another PDMS layer resulting in surfaces
which resemble cell morphology and were called 'positive bioimprints'. Soft
lithography was used to transfer these details from PDMS into different polymers
like polystyrene, tissue culture polystyrene and clinically used block co-polymer
poly (ethylene glycol) terephthalate-poly (butylene terephthalate) (PEGT-PBT).
Results obtained from surface characterization confirmed that fine details of
cells were successfully replicated from cells to different polymer matrices
without any significant loss of information during the different steps of pattern
transfer. HNCs seeded on different polymer surfaces with positive and negative
bioimprints exhibited distinct behaviour. Cells cultured on positive bioimprints
were more spread out and displayed high levels of proliferation compared to those
on negative bioimprints, where cells were more compact with lower proliferation.
PMID- 25850525
TI - Reduction in Endogenous Insulin Secretion is a Risk Factor of Sarcopenia in Men
with Type 2 Diabetes Mellitus.
AB - Sarcopenia has recently attracted widespread attention, because it increases
risks of fall and bedridden. Although patients with type 2 diabetes mellitus
(T2DM) are known to have lower muscle mass of limbs than healthy people, the
mechanism is still unclear. We thus examined the association of muscle mass with
parameters of endogenous insulin secretion such as fasting immunoreactive
insulin, fasting C-peptide immunoreactivity (CPR), and daily urine CPR in 191 men
with T2DM. Muscle mass of arms and legs was evaluated by dual-energy X-ray
absorptiometry, and we calculated relative skeletal muscle index (RSMI), which is
useful for the diagnosis of sarcopenia. Multiple regression analyses adjusted for
age, duration of T2DM, serum creatinine, HbA1c, and insulin-like growth factor-I
showed that each parameter of endogenous insulin was significantly and positively
correlated with muscle mass of arms and legs as well as RSMI (p < 0.05).
Moreover, logistic regression analyses adjusted for confounding factors mentioned
above showed that each parameter of endogenous insulin was significantly lower in
subjects with sarcopenia than those without it (p < 0.05). In conclusion,
reduction in endogenous insulin secretion is an independent risk factor of
sarcopenia in men with T2DM.
PMID- 25850526
TI - The facile realization of luminescence based on one yellow emissive four
coordinate organoboron material.
AB - The orange emissive powders of a boron-containing compound generate red, green,
and blue luminescence after compressing, heating, and volatile acid fuming,
respectively. Thus, stimulus-induced emissions have been facilely realized based
on one organic pi-conjugated material for the first time, to the best of our
knowledge.
PMID- 25850527
TI - Effective practical management of patients with atrial fibrillation when using
new oral anticoagulants.
AB - Practical management of stroke prevention in patients with non-valvular atrial
fibrillation (AF) requires physicians to find the optimal balance between
maximizing prevention of ischaemic stroke and minimizing the risk of bleeding.
Vitamin K antagonists have traditionally been used for stroke prevention in
patients with AF; however, they have been associated with increased risk of
bleeding, particularly intracranial haemorrhage. New oral anticoagulants (OACs)
have shown similar efficacy to the vitamin K antagonist warfarin but with a
reduced risk of bleeding, particularly life-threatening bleeding such as
intracranial haemorrhage. Decisions about which new OAC therapy to use may be
influenced by patient characteristics such as age, renal function, co-medication
use, and bleeding risk. This review uses a case-based approach to highlight the
practical management issues to be considered by the physician when selecting a
new OAC for stroke prevention in patients with non-valvular AF.
PMID- 25850528
TI - Mirror therapy enhances upper extremity motor recovery in stroke patients.
AB - The purpose of this study was to evaluate the effects of mirror therapy program
in addition with physical therapy methods on upper limb recovery in patients with
subacute ischemic stroke. 15 subjects followed a comprehensive rehabilitative
treatment, 8 subjects received only control therapy (CT) and 7 subjects received
mirror therapy (MT) for 30 min every day, five times a week, for 6 weeks in
addition to the conventional therapy. Brunnstrom stages, Fugl-Meyer Assessment
(upper extremity), the Ashworth Scale, and Bhakta Test (finger flexion scale)
were used to assess changes in upper limb motor recovery and motor function after
intervention. After 6 weeks of treatment, patients in both groups showed
significant improvements in the variables measured. Patients who received MT
showed greater improvements compared to the CT group. The MT treatment results
included: improvement of motor functions, manual skills and activities of daily
living. The best results were obtained when the treatment was started soon after
the stroke. MT is an easy and low-cost method to improve motor recovery of the
upper limb.
PMID- 25850529
TI - Fibular strut graft for humeral aneurysmal bone cyst with varus deformity.
AB - PURPOSE: Proximal humerus is a common site for ABC and frequently associated with
varus deformity that limits shoulder abduction. A prospective study was conducted
to evaluate the use of intramedullary non-vascularised autogenous fibular strut
graft for reconstruction without internal fixation. METHODS: A total of 20
patients (12 girls, 8 boys) were managed for proximal humeral ABC with varus
deformity by extended curettage, osteotomy, intramedullary fibular graft and
composite bone substitute. Their ages ranged from 10 to 17 years (average, 13.3
years). The lesion was juxtaphyseal in 16 patients and metaphyseal in 4. All
cysts were active and centrally located type 2. The modified Enneking scoring
system was used for final functional evaluation. Radiological assessment was done
for the extent of defect healing, incorporation of the fibula and correction of
the deformity. RESULTS: After a mean follow-up of 41.2 months (range, 24-74) most
of patients were satisfied and resumed daily activities without pain and with
good range of shoulder movement. One patient complained of shoulder pain 10
months after surgery and was attributed to local recurrence. Limitation of
recreational activity was experienced by one patient. There were no cases of deep
infection, nerve deficit or pathological fracture. No cases of failed healing or
incorporation of the fibula was detected. The improved shoulder abduction was
closely related to the mean correction of the neck shaft angle. CONCLUSIONS: The
technique is proved to be effective in controlling disease, correcting deformity
and improving function.
PMID- 25850530
TI - How to explain the role of magnetic resonance imaging on evaluating tumour
response of osteosarcoma to neoadjuvant chemotherapy: authors' reply.
PMID- 25850532
TI - Influence of different factors on the nitrogenase activity of the engineered
Escherichia coli 78-7.
AB - The engineered Escherichia coli 78-7 is a derivative of E. coli JM109 carrying a
nitrogen fixation (nif) gene cluster composed of nine genes (nifB, nifH, nifD,
nifK, nifE, nifN, nifX, hesA and nifV) and its own sigma(70)-dependent nif
promoter from a gram-positive bacterium Paenibacillus sp. WLY78. The
physiological and biochemical characteristics of the engineered E. coli 78-7 were
analyzed by using Biolog GEN III MicroPlate, with E. coli JM109 and
JM109/pHY300PLK (E. coli JM109 carrying empty vector) as controls. Analysis of 94
phenotypic tests: 71 carbon source utilization assays and 23 chemical sensitivity
tests showed that the engineered E. coli 78-7, E. coli JM109 and JM109/pHY300PLK
gave similar patterns of utilization of various substrates as carbon and energy
sources. Furthermore, the effect of carbon source, nitrogen source, culture
temperature on the nitrogenase activity of the engineered E. coli 78-7 was
investigated. Our study demonstrates that the nif capacity of E. coli 78-7 was
affected significantly by the different culture condition. The significant
nitrogenase activity of E. coli 78-7 were obtained when cells were cultivated in
the medium containing 4 g/l glucose (carbon source) and 2 mM glutamate (nitrogen
source) and at 30 degrees C.
PMID- 25850531
TI - Living standard is related to microregional differences in stroke characteristics
in Central Europe: the Budapest Districts 8-12 Project.
AB - OBJECTIVES: To test whether str oke features relate to living standard within one
city by comparing 2 districts. METHODS: District-8 (D-8) ranks the last, whereas
District-12 (D-12) is the second regarding personal monthly income of the 23
districts of Budapest, Hungary. Stroke cases hospitalized in 2007 were identified
by the database of the National Health Insurance Fund and postal codes for living
address. Case certification was performed by personal visits to the general
practitioners. Demographic data, risk factors and survival status in 2010 were
analyzed using the anonymized database. RESULTS: Three-year case fatality was
36.6 % in D-8 and 31.5 % in D-12 (p = 0.24). Of the fatal cases, men were more
than 12 years younger in D-8 than in D-12 (69.2 +/- 13.3 vs. 82.4 +/- 9.2 years,
p < 0.001). Men died younger than women in D-8 (69.2 +/- 13.3 vs. 75.2 +/- 12.4;
p = 0.036), but not in D-12 (82.4 +/- 9.2 vs. 81.9 +/- 7.3, p = 0.8). Non-treated
hypertension, alcohol dependence, and smoking were significantly more prevalent
in the poor district (p < 0.01 for all). CONCLUSION: In national stroke programs
of former Eastern Block countries, primary prevention should focus especially on
male populations of less wealthy regions.
PMID- 25850533
TI - Cloning, expression, characterization and mutational analysis of the tfdA gene
from Cupriavidus campinensis BJ71.
AB - 2,4-Dichlorophenoxyacetic acid (2,4-D)/alpha-ketoglutarate (alpha-KG) dioxygenase
(TfdA) is an Fe(II)-dependent enzyme that catalyzes the first step in degradation
of the herbicide 2,4-D. Previous studies focused on the tfdA gene in Ralstonia
eutropha JMP134 isolated in Australia. In this study, a new tfdA gene was cloned
from Cupriavidus campinensis BJ71, an effective degrading bacteria from China,
based on the iCOnsensus-DEgenerate Hybrid Oligonucleotide Primers (iCODEHOPs)
protocol, combined with high-efficiency Thermal Asymmetric Interlaced PCR (hiTAIL
PCR). The open reading frame of 861 bp encoded a putative 287 amino acid protein
with a theoretical molecular mass of 32.32 kDa. The gene was overexpressed in
Escherichia coli BL21 (DE3) and the purified TfdA showed optimal activity at pH
6.75 and 30 degrees C. This enzyme was more thermostable and it could use 3
hydrocinnamic acid as substrate, with a similar enzyme activity compared with 2,4
D. TfdA and its variants were created as maltose-binding protein (MBP) tagged
fusion proteins to examine the roles of putative substrate-binding residues. The
MBP-N110A, MBP-V198A and MBP-R207K proteins showed decreased k cat and increased
Km, and MBP-R278A was inactive, suggesting these residues may affect 2,4-D
binding or catalysis.
PMID- 25850534
TI - Aromatase inhibitors in male breast cancer: a pooled analysis.
AB - Although several studies have shown the efficacy of third-generation aromatase
inhibitors (AIs) in women with breast cancer, the role of such molecules remains
elusive in male breast cancer patients. It is also unknown whether the addition
of gonadotropin-releasing hormone (GnRH) analogues to AIs would be a superior
strategy or not. This pooled analysis was conducted in accordance with the PRISMA
guidelines. All studies that examined the efficacy of AIs in metastatic male
breast cancer were considered eligible. Overall, 15 studies (105 cases) were
eligible for this pooled analysis. The mean age of the study sample was 62.8
years. ER status was positive in all eligible cases. AI was given as first line
in 61.5 % of cases. GnRH analogue was co-administered with AI in 37.1 % of cases
(n = 39). CR, PR, SD and PD were achieved in 5.7, 23.8, 37.2 and 33.3 % of cases,
respectively. The median PFS and OS were equal to 10.0 and 39.0 months,
respectively. Co-administration of GnRH analogues was associated with more than
threefold increase in rates of clinical benefit (OR = 3.37, 95 % CI 1.30-8.73)
but did not seem to correlate with better PFS or OS. No statistically significant
associations between the examined outcomes and the other parameters were noted.
Available data suggest that AIs may potentially play a promising role in the
optimal therapeutic strategy for metastatic male breast cancer patients.
Especially, co-administration of AI with a GnRH analogue seems to increase the
rate of clinical benefit and could be more effective, warranting further
consideration.
PMID- 25850535
TI - Comparison of multi-frequency bioimpedance with perometry for the early detection
and intervention of lymphoedema after axillary node clearance for breast cancer.
AB - The importance of early detection of lymphoedema by arm volume measurements
before surgery and repeated measurements after surgery in women undergoing
axillary node clearance (ANC) in order to enable early intervention is
recognised. A prospective multi-centre study was performed which studied the
difference between multi-frequency bioimpedance electrical analysis (BIS) and
perometer arm measurement in predicting the development of lymphoedema. Women
undergoing ANC underwent pre-operative and regular post-operative measurements of
arm volume by both methods. The primary endpoint is the incidence of lymphoedema
(>=10 % arm volume increase compared to contralateral arm by perometer) at 2 and
5 years after ANC. The threshold for intervention in lymphoedema was also
assessed. Out of 964 patients recruited, 612 had minimum 6 months follow-up data.
Using 1-month post-operative measurements as baseline, perometer detected 31
patients with lymphoedema by 6 months (BIS detected 53). By 6 months, 89 % of
those with no lymphoedema reported at least one symptom. There was moderate
correlation between perometer and BIS at 3 months (r = 0.40) and 6 months (r =
0.60), with a sensitivity of 73 % and specificity of 84 %. Univariate and
multivariate analyses revealed a threshold for early intervention of >=5 to <10 %
(p = 0.03). Threshold for early intervention to prevent progression to
lymphoedema is >=5 to <10 % but symptoms alone do not predict lymphoedema. The
modest correlation between methods at 6 months indicates arm volume measurements
remain gold standard, although longer term follow-up is required.
PMID- 25850536
TI - Erratum to: Incidence of BRCA1 and BRCA2 non-founder mutations in patients of
Ashkenazi Jewish ancestry.
AB - In Table 2 of the original publication, the HGVS and legacy nomenclature were
mismatched and the HGVS nomenclature did not correlate with data listed in the
table. The corrected table is listed below.
PMID- 25850537
TI - Psychometric Evaluation of a Consumer-Developed Family-Centered Care Assessment
Tool.
AB - The objective of this study was to create a psychometrically sound measure of
family-centered care, the Family-Centered Care Assessment (FCCA), developed
through a process led by families in collaboration with maternal and child health
leaders. The items for the FCCA scale were initially developed by families of
children and youth with special needs in partnership with pediatric providers and
researchers. Using an Institutional Review Board-approved research protocol, the
questions were revised based on input from focus groups of diverse parents in
three states. Parental responses (N = 790) to the revised 59-item survey were
collected online from families in 49 states. Item distributions uniformly showed
excellent spread. A principal axes factor analysis confirmed the existence of a
single factor. Rasch modeling item analyses identified a reduced subset of 24
items that demonstrated excellent psychometric properties. All items met the
criteria for a linear Rasch scale. Empirical evidence in support of the construct
validity of the 24-item measure was derived: all items had a positive and
substantial item-total correlation; person alpha scale reliability was >0.80 and
the item reliability was >0.90; both separation indices were >2.0; infit and
outfit statistics were within 0.5-1.5; and item difficulties ranged between -2
and +2 logits. Strong rank-ordered associations and large effect sizes were
observed for six indicators of quality of care. This study's family-led process
produced a tool, the FCCA, to measure families' experience of care with excellent
psychometric properties.
PMID- 25850539
TI - Is diabetes a hypercoagulable state? A critical appraisal.
AB - Diabetes mellitus (DM), a chronic disease with an increasing incidence and
prevalence worldwide, is an established risk factor for arterial cardiovascular,
cerebrovascular and peripheral vascular diseases including acute myocardial
infarction, stroke and peripheral artery disease. On the other hand, its role as
independent risk factor for venous thromboembolism (VTE) and for cardioembolic
stroke or systemic embolism (SE) in patients with atrial fibrillation (AF) is
more conflicting. Venous and arterial thromboses have traditionally been regarded
as separate diseases, but recent studies have documented an association between
these vascular complications. Cardiovascular risk factors may contribute to
unprovoked VTE, and VTE may be an early symptomatic event in patients at high
cardiovascular risk, including diabetic patients. Compelling evidences suggest
that DM is associated with a higher risk of development and progression of AF.
Furthermore, in AF patients with a coexisting DM the risk of cardioembolic
stroke/SE appeared increased. Thus, DM has been included as one of the items of
the CHADS2 score and of the subsequent CHA2DS2-VASc score that have been
developed to assess the arterial tromboembolic risk of AF patients. Such a high
incidence of thromboembolic events observed in these clinical subsets may be
attributable to the DM-related prothrombotic state due to a number of changes in
primary and secondary hemostasis. Although of potential clinical interest,
unfortunately, to date, no study has properly evaluated the effects of drugs used
to control blood glucose levels on the risk of venous thromboembolism and
arterial cardioembolic events in patients with DM.
PMID- 25850540
TI - Focal muscle vibration as a possible intervention to prevent falls in elderly
women: a pragmatic randomized controlled trial.
AB - BACKGROUNDS: Different and new approaches have been proposed to prevent the risk
of falling of elderly people, particularly women. AIMS: This study investigates
the possibility that a new protocol based on the focal mechanical muscle
vibration may reduce the risk of falling of elderly women. METHODS: A pragmatic
randomized controlled triple-blind trial with a 6-month follow-up after
intervention randomized 350 women (mean age 73.4 years + 3.11), members of local
senior citizen centers in Rome, into two groups: vibrated group (VG) and control
group (CG). For VG participants a mechanical vibration (lasting 10 min) was
focally applied on voluntary contracted quadriceps muscles, three times a day
during three consecutive days. CG subjects received a placebo vibratory
stimulation. Subjects were tested immediately before (T0) and 30 (T1) and 180
(T2) days after the intervention with the Performance-Oriented Mobility
Assessment (POMA) test. All subjects were asked not to change their lifestyle
during the study. CG underwent sham vibratory treatment. RESULTS: While CG did
not show any statistically significant change of POMA at T1 and T2, VG revealed
significant differences. At T2, ~47% of the subjects who completed the study
obtained the full score on the POMA test and ~59% reached the full POMA score.
CONCLUSIONS: The new protocol seems to be promising in reducing the risk of
falling of elderly subjects.
PMID- 25850541
TI - Multi-muscle coordination during a challenging stance.
AB - PURPOSE: This study aimed to identify the muscle synergies during standing under
various sensory contexts in healthy young adults. METHODS: Sixteen healthy young
adults participated in this study. The 4-min stance task was conducted under
vision (eyes open or eyes closed) and proprioception (standing on ground or
narrowed blocks) manipulated contexts. Electromyography (EMG) of 8 muscles around
the right side of the trunk and leg were recorded and submitted to principal
component analysis (PCA) to extract the muscle synergies. Two-way ANOVA with
repeated measures was employed to test the effect of sensory contexts on the
muscle synergies. RESULTS: PCA extracted three muscle synergies that accounted
for the variance of standing EMG, including the push-back (composed of medial
gastrocnemius, vastus medialis and biceps femoris), push-forward (composed of
tibialis anterior and rectus femoris) and proximal mixed (composed of rectus
abdominis, rector spinae, rectus femoris and biceps femoris) synergies. Block
standing increased the contribution of the push-back synergy while decreased the
contribution of the push-forward synergy. In addition, contribution of the
proximal mixed synergy was higher under ground-standing with eyes open than under
block-standing with eyes open. CONCLUSION: Three muscle synergies were identified
during standing in healthy young adults, and the synergies were affected by
proprioception but not visual disturbance. The push-back and push-forward
synergies showed the opposite response to proprioceptive disturbance, which may
result from their antagonism role. Whether this control regime is used for
elderly adults or patient populations with movement disorder needs to be further
investigated.
PMID- 25850542
TI - [Identification of seniors at risk--primary care: a validated questionnaire
predicting functional decline].
AB - OBJECTIVES: To modify and validate in primary healthcare the Identification of
Seniors At Risk (ISAR) screening questionnaire to identify older persons at
increased risk of functional decline and to compare this strategy with risk
stratification by age alone. STUDY DESIGN AND SETTING: Prospective development
(n=790) and validation cohorts (n=2,573) of community-dwelling persons aged >=70
years. Functional decline at 12 months was defined as an increase of at least one
point on the modified Katz-activities of daily living index score compared with
baseline or death. RESULTS: Three items were independently associated with
functional decline: age (odds ratio [OR] 1.06 per year; 95% confidence interval
[CI] 1.02, 1.10) dependence in instrumental activities of daily living (OR: 2.17;
95% CI: 1.46, 3.22), and impaired memory (OR: 2.22; 95% CI: 1.41, 3.51). The area
under the receiver operating characteristics curve (AUC) range of the ISAR
primary care model was 0.67-0.70 and 40.6% was identified at increased risk.
Validation yielded an AUC range of 0.63-0.64. Age>=75 years alone yielded an AUC
range of 0.56-0.57 and identified 65.0% at increased risk in the validation
cohort. CONCLUSION: Although the ISAR-Primary Care (ISAR-PC) has moderate
predictive value, application of the ISAR-PC is more efficient than selection
based on age alone in identifying persons at increased risk of functional
decline. This paper is a translated and adjusted version based on a publication
in Journal of Clinical Epidemiology, 67 (2014) 1121-1130.
PMID- 25850543
TI - Environmentally Realistic Doses of Cadmium as a Possible Etiologic Agent for
Idiopathic Pathologies.
AB - Cadmium is a heavy metal of increasing environmental concern that has long been
associated to several human pathological processes. Recent population surveys
have correlated cadmium non-occupational exposure to widespread idiopathic
pathologies. Food and tobacco are reported to be the main exposure sources of
cadmium to the general population, as phosphate fertilizers are rich in such a
metal, thus contaminating the crops. Although its mechanisms of toxicity are not
a consensus in the literature, it is well established that reactive oxygen
species play a key role in this process, leading to the oxidation of several
biological molecules. We have therefore assessed whether three environmentally
realistic doses of cadmium alter the oxidative status of Wistar rat testis and
eventually result in histological damages. Our results show that even the lowest
environmental dose of cadmium was able to disturb the endogenous antioxidant
system in Wistar testis, although an increase in lipid peroxidation was observed
only within the group exposed to the highest environmental dose. Despite that no
remarkable morphological changes were observed in any group, significant
alterations in blood vessel lumen were reported for some cadmium-exposed animals,
suggesting that endothelium is one of the primary targets involved in cadmium
toxicity.
PMID- 25850544
TI - Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages
are Prevented by the Combined Action of Folate and Vitamin B12.
AB - Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C)
metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic
disposition and detoxification of the biological systems. Vitamin B12 and folate,
the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 MUg,
respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy
in the protection from mutagenic DNA-breakage and tissue damages. The selected
tissues like intestine (first-pass site), liver (major xenobiotic metabolizer)
and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6
ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions
were monitored. Our earlier studies on arsenic-exposed humans can correlate
carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of
physiological/therapeutic dose of vitamin B12 and folate protected the rodents
significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay)
and hepatic and renal tissue degeneration (histo-architecture, HE staining). The
level of arsenic-induced free-radical products (TBARS and conjugated diene) was
significantly declined by the restored actions of several antioxidants viz.
urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide
dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase,
transaminases, urea and creatinine (hepatic and kidney toxicity marker), and
lactate dehydrogenase (tissue degeneration marker) were significantly impaired in
the arsenic-fed group. But a significant protection was evident in the vitamin
supplemented group. In conclusion, the combined action of folate and B12 results
in the restitution in the 1C metabolic pathway and cellular methyl pool. The
cumulative outcome from the enhanced arsenic methylation and antioxidative
capacity was protective against arsenic induced mutagenic DNA breakages and
tissue damages.
PMID- 25850545
TI - Expression of Iodotyrosine Deiodinase in Thyroid and Other Organs in Iodine
Deficient and Iodine-Excess Rats.
AB - In mammals, iodothyronine deiodinase and iodotyrosine deiodinase (IYD) are known
to catalyze the reductive dehalogenation. IYD is a critical enzyme in maintaining
iodine homeostasis. Advances in the study of iodothyronine deiodinase have been
published steadily; research on IYD has been slow on its function and regulation.
We studied the expression of IYD in thyroid, liver, and kidney in conditions such
as iodine deficiency and excess to determine its regulation and role in iodine
recycling. Sixty 4-week-old female Wistar rats were randomly divided into two
groups, with each group containing three subgroups. The rats were fed with
different iodine intake for 3 months. After 3 months, all the rats were
sacrificed, and the expression of IYD in thyroid, liver, and kidney of the rats
were determined. We found that the expression of thyroidal IYD in 0.3-fold-iodine
intake group was significantly higher as compared with the low-iodine feed
control group (p < 0.01), whereas the expression in 6-fold-iodine intake group
was significantly decreased as compared with normal-iodine feed control group (p
< 0.01). However, the variation of IYD expression in thyroid was not similar to
liver and kidney. In conclusion, iodine deficiency results in an increased
expression of IYD in thyroid, whereas excess iodine decreases the expression of
thyroidal IYD. In humans, daily iodine intake of <75 or >500 MUg can affect the
expression of thyroidal IYD. The safety range of iodine intake is narrow. In
addition, further investigations are required to study the expression and
regulation of IYD in various organs.
PMID- 25850546
TI - A practical approach to avoiding iatrogenic Creutzfeldt-Jakob disease (CJD) from
invasive instruments.
AB - Potential Creutzfeldt-Jakob disease instrument-contamination events continue to
occur, causing widespread hospital and patient concern. We propose the use of a
combination of diagnostic tests (ie, spinal fluid for 14-3-3 protein or nasal
brushing for misfolded prion protein) and instrument handling procedures (ie,
using a regional set of dedicated instruments), which if applied to all patients
admitted with symptoms of either dementia or cerebellar disease, should eliminate
the risk of iatrogenic instrument infection.
PMID- 25850548
TI - Prostate cancer: New biomarker panel prognosticates patient survival.
PMID- 25850549
TI - Intermediate-stage HCC--upfront resection can be feasible.
PMID- 25850550
TI - Immunotherapy: CheckMate--has nivolumab beaten melanoma?
PMID- 25850551
TI - Lung cancer: Implementing lung-cancer screening--oncological 'grey areas'.
PMID- 25850552
TI - Intermediate-stage HCC--upfront resection can be feasible.
PMID- 25850554
TI - Surgical issues in patients with breast cancer receiving neoadjuvant
chemotherapy.
AB - Early randomized trials of the addition of neoadjuvant chemotherapy (NACT) to the
treatment regimen of patients with breast cancer failed to demonstrate an
improvement in overall survival compared with conventional adjuvant therapy;
nevertheless, the increased opportunities for breast conservation, owing to
downstaging of the primary tumour, and enthusiasm regarding the potential to
tailor systemic therapy based on responses observed in the neoadjuvant setting,
resulted in the adoption of this approach as a useful clinical tool. That the
effectiveness of NACT varies by molecular subtype is becoming increasingly clear,
and although the potential of tailoring adjuvant systemic therapy based on
treatment response before surgery remains to be realized, the increasing rates of
pathological complete response following NACT have had a considerable impact on
locoregional treatment considerations. For example, NACT reduces the need for
mastectomy and axillary lymph-node dissection, thus decreasing the morbidity of
surgery, without compromising outcomes. However, selection of the ideal
candidates for preoperative chemotherapy remains critical, and personalizing
local therapy based on the degree of response is the subject of ongoing clinical
trials. This article reviews the current issues surrounding surgery of the breast
and axilla in patients with breast cancer receiving NACT.
PMID- 25850555
TI - Production of bacteriocin-like inhibitory substance by Bifidobacterium lactis in
skim milk supplemented with additives.
AB - Bacteriocins are natural compounds used as food biopreservatives instead of
chemical preservatives. Bifidobacterium animalis subsp. lactis (Bifid. lactis)
was shown to produce a bacteriocin-like inhibitory substance (BLIS) able to
inhibit the growth of Listeria monocytogenes selected as an indicator
microorganism. To enhance this production by the strain Bifid. lactis BL 04, skim
milk (SM) was used as a fermentation medium either in the presence or in the
absence of yeast extract, Tween 80 or inulin as stimulating additives, and the
results in terms of bacterial growth and BLIS production were compared with those
obtained in a traditional high cost complex medium such as Man, Rogosa and Sharpe
(MRS). To this purpose, all the cultivations were carried out in flasks at 200
rpm under anaerobic conditions ensured by a nitrogen flowrate of 1.0 L/min for 48
h, and BLIS production was quantified by means of a modified agar diffusion assay
at low values of both temperature and concentration of List. monocytogenes.
Although all these ingredients were shown to exert positive influence on BLIS
production in both media, yeast extract and SM were by far the best ingredient
and the best medium, respectively, allowing for a BLIS production at the late
exponential phase of 2000 AU/ml.
PMID- 25850557
TI - Effectiveness and Mechanisms of Defluorination of Perfluorinated Alkyl Substances
by Calcium Compounds during Waste Thermal Treatment.
AB - The mineralization of perfluorinated alkyl substances (PFASs) by calcium
compounds during the waste thermal treatment was systemically studied. Different
calcium compounds showed different mineralization efficiencies of PFASs during
the thermal process, owing to the different reaction mechanisms. Calcium
hydroxide was recommended as the most effective Ca reagent for PFAS
defluorination because the carbon-fluorine bonds in PFASs can be converted to
carbon-hydrogen bonds via the hydrodefluorination reaction. PFASs with different
chain lengths and functional groups were further investigated for their
potentially different mineralization behavior. The results showed that the chain
length of PFASs had an insignificant effect on the mineralization efficiency by
calcium hydroxide. The thermogravimetric analysis-differential thermal analysis
(TGA-DTA) also revealed that perfluorooctanesulfonate (PFOS) and
perfluorohexanesulfonate (PFHxS) (with different chain lengths) had a similar
thermal behavior. However, PFASs with different functional groups showed
different mineralization behavior with calcium hydroxide in relation to their
different thermal decomposition temperatures. Finally, the mineralization ratio
of polytetrafluoroethylene (PTFE) particles by calcium hydroxide could reach 80%
or higher when the temperature was above 400 degrees C. The gas
chromatography/mass spectrometry (GC/MS) results demonstrated much reduced
production of gaseous fluorocarbon fragments during PTFE decomposition when
coexisting with calcium hydroxide.
PMID- 25850553
TI - Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical
update.
AB - During the past decade, cancer stem cells (CSCs) have been increasingly
identified in many malignancies. Although the origin and plasticity of these
cells remain controversial, tumour heterogeneity and the presence of small
populations of cells with stem-like characteristics is established in most
malignancies. CSCs display many features of embryonic or tissue stem cells, and
typically demonstrate persistent activation of one or more highly conserved
signal transduction pathways involved in development and tissue homeostasis,
including the Notch, Hedgehog (HH), and Wnt pathways. CSCs generally have slow
growth rates and are resistant to chemotherapy and/or radiotherapy. Thus, new
treatment strategies targeting these pathways to control stem-cell replication,
survival and differentiation are under development. Herein, we provide an update
on the latest advances in the clinical development of such approaches, and
discuss strategies for overcoming CSC-associated primary or acquired resistance
to cancer treatment. Given the crosstalk between the different embryonic
developmental signalling pathways, as well as other pathways, designing clinical
trials that target CSCs with rational combinations of agents to inhibit possible
compensatory escape mechanisms could be of particular importance. We also share
our views on the future directions for targeting CSCs to advance the clinical
development of these classes of agents.
PMID- 25850558
TI - Outcomes of delayed total hip arthroplasty in patients with a previous
ipsilateral acetabular fracture.
AB - Post-traumatic arthritis of the hip can develop in 12-57% of patients after an
acetabular fracture. Once it develops, salvage treatment options include
arthroplasty or arthrodesis. Delayed total hip arthroplasty (THA) has been shown
to be a viable treatment option to decrease pain, improve stability and increase
functional outcomes. Using cemented designs, earlier long-term studies reported
satisfactory functional outcomes of delayed THA used to treat previously failed
acetabular fractures. However, high aseptic loosening rates were also observed.
Recent advances in cementless acetabular designs have shown comparable functional
outcomes and loosening rates compared to those undergoing THA for non-traumatic
arthritis. However, even with improvements in functional and radiographic
outcomes, unique complications are commonly encountered in patients with previous
acetabular fractures, including heterotopic bone around the hip, increased
operative times and blood loss, aseptic loosening, sciatic nerve injury and
dislocation. The outcomes and complications of delayed THA in patients with
previous acetabular fracture will be reviewed.
PMID- 25850559
TI - Geleophysic dysplasia: a novel in-frame deletion of a tandem repeat in the
ADAMTSL2 gene.
PMID- 25850560
TI - Intake of energy-dense snack foods and drinks among Dutch children aged 7-12
years: how many, how much, when, where and which?
AB - OBJECTIVE: To describe the energy-dense snack food (EDSF) and energy-dense drink
(EDD) consumption of children in the Netherlands and investigate subgroup
differences. The amounts consumed, eating occasions, places of consumption and
consumed types are reported. DESIGN: Twenty-four hour dietary recall data were
used to describe the EDSF and EDD consumption. Subgroup differences concerning
these intakes were identified with ANCOVA. SETTING: Dutch National Food
Consumption Survey 2007-2010. SUBJECTS: Children (n 860) aged 7-12 years.
RESULTS: The mean number of EDSF events was 3.3 (sd 1.6) per day, yielding 1569.7
(sd 928.7) kJ. Average EDD consumption was 594.2 (sd 342.3) ml/d, yielding 737.2
(sd 495.9) kJ. Over 90 % of the children consumed more energy from non-core foods
per day than recommended. Differences in EDSF and EDD consumption were found
between several subgroups. Most importantly, we found higher intakes among older
children and children with low educated mothers. Almost half of the EDSF events
took place in the afternoon and at home. Cookies and sweets were consumed during
half of the EDSF events. Almost one-third of the EDD were consumed in the
afternoon. The majority of these drinks were consumed at home and most were soft
drinks. CONCLUSIONS: The results demonstrate that snack food and drink
consumption is highly prevalent among Dutch children. Health promotion efforts
addressing these behaviours are warranted and the present study could accelerate
these initiatives. Focusing on children with low educated parents and on snacking
at home after school offers the greatest potential to reduce snack food and drink
intakes.
PMID- 25850561
TI - The maturation of research into the avian hippocampal formation: Recent
discoveries from one of the nature's foremost navigators.
AB - For more than 30 years, a growing number of researchers have been attracted to
the challenge of understanding the neurobiological organization of the avian
hippocampal formation (HF) and its relationship to the remarkable spatial
cognitive abilities of birds. In this selective review, we highlight recent
anatomical and developmental findings that reveal a HF design that defies any
simple comparison to the mammalian hippocampus and leaves unanswered the
seemingly enduring question of whether a dentate gyrus homologue is to be found
in HF. From a functional perspective, we highlight the recent discoveries that
implicate HF in the use of space for memory pattern segregation and continued
interest in the role HF neurogenesis may play in supporting memory function and
its relationship to memory decline in aging birds. We also summarize data that
nurture a fundamental reinterpretation of the role of HF in spatial cognition by
suggesting HF involvement in spatial perception antecedent to any memory
formation. Given the disproportionate adaptive significance of space for birds,
which has led to the evolution of their exceptional navigational and memory
abilities, there is little doubt that the avian HF will continue to provide
important and unexpected insights into the neural basis of spatial cognition.
PMID- 25850562
TI - Short-term population-based non-linear concentration-response associations
between fine particulate matter and respiratory diseases in Taipei (Taiwan): a
spatiotemporal analysis.
AB - Fine particulate matter <2.5 MUm (PM2.5) has been associated with human health
issues; however, findings regarding the influence of PM2.5 on respiratory disease
remain inconsistent. The short-term, population-based association between the
respiratory clinic visits of children and PM2.5 exposure levels were investigated
by considering both the spatiotemporal distributions of ambient pollution and
clinic visit data. We applied a spatiotemporal structured additive regression
model to examine the concentration-response (C-R) association between children's
respiratory clinic visits and PM2.5 concentrations. This analysis was separately
performed on three respiratory disease categories that were selected from the
Taiwanese National Health Insurance database, which includes 41 districts in the
Taipei area of Taiwan from 2005 to 2007. The findings reveal a non-linear C-R
pattern of PM2.5, particularly in acute respiratory infections. However, a PM2.5
increase at relatively lower levels can elevate the same-day respiratory health
risks of both preschool children (<6 years old) and schoolchildren (6-14 years
old). In preschool children, same-day health risks rise when concentrations
increase from 0.76 to 7.44 MUg/m(3), and in schoolchildren, same-day health risks
rise when concentrations increase from 0.76 to 7.52 MUg/m(3). Changes in PM2.5
levels generally exhibited no significant association with same-day respiratory
risks, except in instances where PM2.5 levels are extremely high, and these
occurrences do exhibit a significant positive influence on respiratory health
that is especially notable in schoolchildren. A significant high relative rate of
respiratory clinic visits are concentrated in highly populated areas. We
highlight the non-linearity of the respiratory health effects of PM2.5 on
children to investigate this population-based association. The C-R relationship
in this study can provide a highly valuable alternative for assessing the effects
of ambient air pollution on human health.
PMID- 25850563
TI - T-DNA insertion in aquaporin gene AtPIP1;2 generates transcription profiles
reminiscent of a low CO2 response.
AB - Results from CO2 diffusion studies and characterization of Arabidopsis thaliana
aquaporin AtPIP1;2 T-DNA insertion lines support the idea that specific
aquaporins facilitate the diffusion of CO2 through biological membranes. However,
their function as CO2 diffusion facilitators in plant physiology is still a
matter of debate. Assuming that a lack of AtPIP1;2 causes a characteristic
transcriptional response, we compared data from a AtPIP1;2 T-DNA insertion line
obtained by Illumina sequencing, Affymetrix chip analysis and quantitative RT-PCR
to the transcriptome of plants grown under drought stress or under low CO2
conditions. The plant reaction to the deficit of AtPIP1;2 was unlike drought
stress responses but comparable with that of low CO2 conditions. In addition, we
observed a phenotype characteristic to plants grown under low CO2 . The findings
support the hypothesis that the AtPIP1;2 function in plant physiology is not to
facilitate water but CO2 diffusion.
PMID- 25850564
TI - Antagonistic effect of helpers on breeding male and female survival in a
cooperatively breeding bird.
AB - 1. Cooperatively breeding species are typically long lived and hence, according
to theory, are expected to maximize their lifetime reproductive success through
maximizing survival. Under these circumstances, the presence of helpers could be
used to lighten the effort of current reproduction for parents to achieve higher
survival. 2. In addition, individuals of different sexes and ages may follow
different strategies, but whether male and female breeders and individuals of
different ages benefit differently from the presence of helpers has often been
overlooked. Moreover, only one study that investigated the relationship between
parental survival and the presence of helpers used capture-mark-recapture
analyses (CMR). These methods are important since they allow us to account for
the non-detection of individuals that are alive in the population but not
detected, and thus, the effects on survival and recapture probability to be
disentangled. 3. Here, we used multi-event CMR methods to investigate whether the
number of helpers was associated with an increase in survival probability for
male and female breeders of different ages in the sociable weaver Philetairus
socius. In this species, both sexes reduce their feeding rate in the presence of
helpers. We therefore predicted that the presence of helpers should increase the
breeders' survival in both sexes, especially early in life when individuals
potentially have more future breeding opportunities. In addition, sociable weaver
females reduce their investment in eggs in the presence of helpers, so we
predicted a stronger effect of helpers on female than male survival. 4. As
expected we found that females had a higher survival probability when breeding
with more helpers. Unexpectedly, however, male survival probability decreased
with increasing number of helpers. This antagonistic effect diminished as the
breeders grew older. 5. These results illustrate the complexity of fitness costs
and benefits underlying cooperative behaviours and how these may vary with the
individuals' sex and age. They also highlight the need for further studies on the
sex-specific effects of helpers on survival.
PMID- 25850565
TI - Disseminated histoplasmosis as pseudo Richter's transformation in a patient with
chronic lymphocytic leukemia.
PMID- 25850567
TI - Microscale Sensing of Oxygen via Encapsulated Porphyrin Nanofibers: Effect of
Indicator and Polymer "Core" Permeability.
AB - Biomimetic polymer nanofibers integrate sensing capabilities creating utility
across many biological and biomedical applications. We created fibers consisting
of either a poly(ether sulfone) (PES) or a polysulfone (PSU) core coated by a
biocompatible polycaprolactone (PCL) shell to facilitate cell attachment. Oxygen
sensitive luminescent probes Pt(II) meso-tetra(pentafluorophenyl)porphine
(PtTFPP) or Pd(II) meso-tetra(pentafluorophenyl)porphine (PdTFPP), were
incorporated in the core via single-step coaxial electrospinning providing
superior sensitivity, high brightness, linear response, and excellent stability.
Both PES-PCL and PSU-PCL fibers provide more uniform probe distribution than
polydimethylsiloxane (PDMS). PSU-based sensing fibers possessed optimum
sensitivity due to their relatively higher oxygen permeability. During exposure
to 100% nitrogen and 100% oxygen, PES-PCL fiber displayed an I0/I100 value of
6.7; PSU-PCL exhibited a value of 8.9 with PtTFPP as the indicator. In contrast,
PdTFPP-containing fibers possess higher sensitivity due to the long porphyrin
lifetime. The corresponding I0/I100 values were 80.6 and 106.7 for the PES-PCL
and PSU-PCL matrices, respectively. The response and recovery times were
0.24/0.39 s for PES-PCL and 0.38/0.83 s for PSU-PCL which are 0.12 and 0.11 s
faster, respectively, than the Pt-based porphyrin in the same matrices.
Paradoxically, lower oxygen permeabilities make these polymers better suited to
measuring higher (i. e., ~20%) oxygen contents than PDMS. Individual fiber
sensing was studied by fluorescence spectrometry and at a sub-micrometer scale by
total internal reflection fluorescence (TIRF). Specific polymer blends relate
polymer composition to the resulting sensor properties. All compositions
displayed linear Stern-Volmer plots; sensitivity could be tailored by matrix or
the sensing probe selection.
PMID- 25850566
TI - Flaxseed reduces the pro-carcinogenic micro-environment in the ovaries of normal
hens by altering the PG and oestrogen pathways in a dose-dependent manner.
AB - The objective of the present study was to find the optimum dose of flaxseed that
would decrease PG and alter oestrogen pathway endpoints implicated in ovarian
cancer. In the study, four groups of fifty 1.5-year-old chickens were fed
different amounts of flaxseed (0, 5, 10 or 15% of their total diet) for 4 months
and were then killed to collect blood and tissues. Levels of flaxseed lignan
metabolites, Enterolactone (EL) and Enterodiol (ED) were measured in the serum,
liver and ovaries by liquid chromatography-MS/MS, and n-3 and n-6 fatty acid (FA)
levels were measured by GC. The effects of the varied flaxseed doses were
assessed by measuring levels of PGE2 and oestrogen metabolites (16-hydroxyestrone
(16-OHE1) and 2-hydroxyestrone (2-OHE1)) as well as by analysing the expression
of the oestradiol metabolising enzymes CYP3A4 (cytochrome p450, family 3,
subfamily A, polypeptide 4), CYP1B1 (cytochrome p450, family 1, subfamily B,
polypeptide 1) and CYP1A1 (cytochrome p450, family 1, subfamily A, polypeptide 1)
and that of oestrogen receptor alpha (ERalpha) in the ovaries. The ratio of n-3:n
FA increased with an increase in flaxseed supplementation and corresponded to a
dose-dependent decrease in cyclo-oxygenase-2 protein and PGE2 levels. EL and ED
increased in the serum, liver and ovaries with increased concentrations of
flaxseed. Flaxseed decreased the expression of ERalpha in the ovaries. The ratio
of 2-OHE1:16-OHE1 in the serum increased significantly in the 15% flaxseed diet,
and there was a corresponding increase in CYP1A1 in the liver and decrease in
CYP3A4 in the ovaries. CYP1B1 mRNA also decreased with flaxseed diet in the
ovaries. The 15% flaxseed-supplemented diet significantly decreased inflammatory
PGE2, ERalpha, CYP3A4, CYP1B1 and 16-OHE1, but it increased CYP1A1 and 2-OHE1,
which thus reduced the inflammatory and pro-carcinogenic micro-environment of the
ovaries.
PMID- 25850568
TI - Number of active electrodes at time of staged tined lead interstim implant does
not impact clinical outcomes.
AB - OBJECTIVES: To determine: (1) if obtaining motor response on <4 tined lead
electrodes at time of placement affects subjective and objective clinical outcome
and (2) voltage requirements to elicit motor response at implant and first
postoperative visit number based on number of responding electrodes. METHODS: We
reviewed our prospective neuromodulation database to identify patients with
unilateral S3 lead placement and motor response (bellows +/- toe flexion) on
stimulation of 1-4 electrodes, then grouped by number of active electrodes at
lead placement. Stage 1 success, reoperation and reprogramming rates, mean
voltage at implant and first postoperative visit, and Interstitial Cystitis
Symptom/Problem Indices (ICSI-PI) were analyzed using Pearson's Chi-square,
Fisher's exact, Kruskal-Wallis or Wilcoxon rank tests. RESULTS: Two hundred forty
four patients met inclusion criteria, categorized into 1-2 (n = 25), 3 (n = 48),
and 4 active electrodes (n = 171). There were no significant differences between
groups in terms of age, indications for neuromodulation, or stage 1 success. At
implant, patients with <4 active electrodes required higher mean voltages for
motor responses (5.9, 4.9, and 3.9 volts for each group respectively; P <
0.0001). Mean voltages for sensory threshold at first postoperative programming
were 1.5 +/- 1.5, 0.9 +/- 1.0, and 0.8 +/- 1.0, respectively (P = 0.08). Overall
reoperation rates, and reprogramming sessions at 24 months did not differ (P =
0.72 and P = 0.50). ICSI-PI scores improved similarly in all groups. CONCLUSIONS:
Motor response on four electrodes is not necessary for successful stage 1 trial.
Despite higher voltage requirements in those with <4 active electrodes at
implant, this difference was not observed at initial postoperative programming.
Neurourol. Urodynam. 35:625-629, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 25850570
TI - Is there an association between metabolic syndrome and cognitive function in very
old adults? The Newcastle 85+ Study.
AB - OBJECTIVES: To determine, using data from the Newcastle 85+ Study, whether there
is an association between modern diagnostic criteria for metabolic syndrome
(MetS) and cognitive function in very old adults (>=85) and whether inflammation,
physical activity, or diabetes mellitus status affects this association. DESIGN:
Longitudinal, population-based cohort study. SETTING: Newcastle and North
Tyneside, United Kingdom. PARTICIPANTS: Community-dwelling and institutionalized
men and women recruited through general practices (N = 845). MEASUREMENTS: MetS
was defined according to the National Cholesterol Education Program (NCEP) Adult
Treatment Panel III (ATP III) criteria. Cross-sectional and prospective (up to 5
years of follow-up) associations between MetS and global cognitive function
(assessed using the Mini-Mental State Examination (MMSE)) and between MetS and
attention and episodic memory (assessed using the Cognitive Drug Research
battery) were performed. RESULTS: MetS was not associated with cognitive function
at baseline or cognitive change over time. Lack of association was not because
MetS was predictive of subsequent mortality. Of the individual components of the
MetS criteria, high blood pressure was associated with better cognitive function
at baseline (MMSE: beta (standard error (SE)) = -0.716 (0.152), P < .001), and
low high-density lipoprotein cholesterol was associated with poorer global
cognitive function at baseline (MMSE: 0.436 (0.131), P = .001). CONCLUSION: The
association between MetS and cognitive decline, which has been described in
younger populations (<75), was not apparent in this population of individuals
aged 85 and older at baseline.
PMID- 25850571
TI - Applications of yeast-based signaling sensor for characterization of antagonist
and analysis of site-directed mutants of the human serotonin 1A receptor.
AB - The monoamine neurotransmitter serotonin (5-HT) regulates a wide spectrum of
human physiology through the 5-HT receptor family. One such receptor, the 5-HT1A
receptor (HTR1A), is the most widely studied subtype and represents a significant
molecular target in medicinal and therapeutic fields. Yeast-based fluorescent
reporter systems have proven to be especially useful for GPCR assays, since
detection using a fluorescent reporter considerably simplifies measurement
procedures. However, previously reported systems using enhanced green fluorescent
protein (EGFP) as the reporter in yeast still showed low signal-to-noise (S/N)
ratios, making EGFP difficult to apply as an easily accessible tool. Therefore,
we constructed a refined yeast-based GPCR biosensor employing a high-sensitivity
strain that incorporated both a Galpha-engineered receptor and a fluorescent
reporter (ZsGreen). As we report here, the refined yeast-based fluorescent
biosensor was applied successfully to antagonist characterization and analysis of
site-directed mutants of the HTR1A receptor. Pindolol, a known antagonist of
HTR1A, specifically inhibited agonist-induced signaling, demonstrating the ease
of evaluating inhibition effects using our reporter strain. Characterization of
site-specific receptor mutants confirmed the role of specific targeted residues,
including the highly conserved DRY motif, in the activation of HTR1A. Thus, our
refined yeast biosensor strain, which incorporates a ZsGreen reporter and an
engineered Galpha receptor, is expected to serve as a simple and practical
sensing tool for evaluating the ligand candidates and defining residues important
to the function of human GPCRs. Biotechnol.
PMID- 25850569
TI - The metabolic control of schistosome egg production.
AB - Schistosomiasis is a neglected tropical disease caused by infection with
trematode parasites of the genus Schistosoma. Despite ongoing treatment
programmes, the prevalence of schistosomiasis has failed to decline and the
disease remains a cause of severe morbidity in millions of people. Understanding
the biology of egg production by schistosomes is critical since eggs allow
transmission of the infection, and when trapped in host tissues induce the immune
responses that are responsible for the pathologic changes that underlie disease
development. Unusually among trematodes, adult schistosomes exhibit sexual
dimorphism and display a fascinating codependency in that the female is dependent
on the male to grow and sexually mature. Thus, virgin females are developmentally
stunted compared with females from mixed-sex infections and are unable to lay
eggs. Moreover, fecund female schistosomes rapidly lose the ability to produce
eggs when placed in tissue culture. Here we discuss the metabolic regulation of
egg production in schistosomes, and in particular the critical role played by
fatty acid oxidation in this process.
PMID- 25850572
TI - Outcomes and cost minimisation associated with outpatient parenteral
antimicrobial therapy (OPAT) for foot infections in people with diabetes.
AB - OBJECTIVE: To determine clinical outcomes in patients with diabetic foot
infections receiving outpatient parenteral antimicrobial therapy (OPAT), to
evaluate cost savings from the use of OPAT and to analyse demographic, clinical
and laboratory data that may predict OPAT failure. RESEARCH DESIGN AND
METHODOLOGY: A retrospective cohort analysis was conducted between 1 January 2007
and 7 July 2012 at a tertiary referral hospital in metropolitan Sydney. Patients
with diabetic foot infection were identified from the outpatient parenteral
antimicrobial therapy database. Demographic, clinical, laboratory and operative
report data were obtained from patient charts and electronic medical records.
Potential cost savings were calculated on the estimated cost of expenditure
versus the expected savings. Linear regression was used to explore outcomes
associated with outpatient parenteral antimicrobial therapy failure. RESULTS:
Fifty-nine patients were identified over the 5-year study period. The outpatient
parenteral antimicrobial therapy success rate for diabetic foot infections was
88%. Following the resolution of the primary episode of infection, new infective
episodes within the study period were high (n = 26, 44%). Regression analysis of
variables for OPAT failure failed to indicate any factors reaching statistical
significance. A total of 1569 days were saved by using outpatient parenteral
antimicrobial therapy for an estimated total cost saving of $983,645 or $16,672
per patient. CONCLUSION: Outpatient intravenous therapy for diabetic foot
infections is an effective mode of treatment that can contribute to significant
healthcare savings. High re-infection rates associated with diabetes foot
ulceration in this population underline the need for close monitoring and
management of these patients in multidisciplinary high-risk foot setting.
PMID- 25850573
TI - Cerebral white matter fractional anisotropy and tract volume as measured by MR
imaging are associated with impaired cognitive and motor function in pediatric
posterior fossa tumor survivors.
AB - BACKGROUND: Disease and therapy cause brain damage and subsequent functional loss
in pediatric patients with posterior fossa tumors. Treatment-related toxicity
factors are resection in patients with pilocytic astrocytoma (PA) and,
additionally, cranio-spinal irradiation together with chemotherapy in patients
with medulloblastoma (MB). We tested whether damage to white matter (WM) as
revealed by diffusion tensor MR imaging (DTI) correlated with specific cognitive
and motor impairments in survivors of pediatric posterior fossa tumors.
PROCEDURES: Eighteen MB (mean age +/- SD, 15.2 +/- 4.9 y) and 14 PA (12.6 +/- 5.0
y) survivors were investigated with DTI on a 3-Tesla-MR system. We identified
fractional anisotropy (FA) of WM, the volume ratio of WM to gray matter and
cerebrospinal fluid (WM/GM + CSF), and volume of specific frontocerebellar
tracts. Ataxia was assessed using the International Cooperative Ataxia Rating
Scale (ICARS), while the Wechsler Intelligence Scale for Children determined full
scale intelligence quotients (FSIQ). Amsterdam Neuropsychological Tasks (ANT) was
used to assess processing speed. Handwriting automation was analyzed using a
digitizing graphic tablet. RESULTS: The WM/GM + CSF ratio correlated
significantly with cognitive measures (IQ, P = 0.002; ANT baseline speed, P =
0.04; ANT shifting attention, P = 0.004). FA of skeletonized tracts correlated
significantly with FSIQ (P = 0.008), ANT baseline speed (P = 0.028) and ANT
shifting attention (P = 0.045). Moreover, frontocerebellar tract volumes
correlated with both the FSIQ (P = 0.011) and ICARS (P = 0.007). CONCLUSION: DTI
provides a method for quantification of WM damage by tumor and by therapy
associated effects in survivors of pediatric posterior fossa tumors. DTI-derived
WM integrity may be a representative marker for cognitive and motor
deterioration.
PMID- 25850574
TI - Effects of early vitamin D deficiency rickets on bone and dental health, growth
and immunity.
AB - Vitamin D deficiency is associated with adverse health outcomes, including
impaired bone growth, gingival inflammation and increased risk for autoimmune
disease, but the relationship between vitamin D deficiency rickets in childhood
and long-term health has not been studied. In this study, we assessed the effect
of early vitamin D deficiency on growth, bone density, dental health and immune
function in later childhood to determine if children previously diagnosed with
rickets were at greater risk of adverse health outcomes compared with healthy
children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone,
bone mineral density, anthropometric measures, dietary habits, dental health,
general health history, and markers of inflammation in 14 previously diagnosed
rickets case children at Children's Hospital Oakland Research Center. We compared
the findings in the rickets cases with 11 healthy children selected from the
population of CHO staff families. Fourteen mothers of the rickets cases, five
siblings of the rickets cases, and seven mothers of healthy children also
participated. Children diagnosed with vitamin D deficiency rickets had a greater
risk of fracture, greater prevalence of asthma, and more dental enamel defects
compared with healthy children. Given the widespread actions of vitamin D, it is
likely that early-life vitamin D deficiency may increase the risk of disease
later in childhood. Further assessment of the long-term health effects of early
deficiency is necessary to make appropriate dietary recommendations for infants
at risk of deficiency.
PMID- 25850575
TI - CD14++ CD16+ HLA-DR+ Monocytes in Peripheral Blood are Quantitatively Correlated
with the Severity of Pre-eclampsia.
AB - PROBLEM: We aim to investigate the proportion and absolute counts of peripheral
blood monocyte subsets in women with normal pregnancy (NP) and pre-eclampsia
(PE), and their correlation with the clinical manifestation and severity of PE.
METHOD OF STUDY: Peripheral blood was obtained from women with NP (n = 30), mild
PE (MPE, n = 15) and severe PE (SPE, n = 30). The proportion and absolute counts
of CD16(+) monocytes and the subsets including intermediate (CD14(++) CD16(+) HLA
DR(+) ) and non-classical (CD14(+) CD16(++) HLA-DR(+) ) monocytes were determined
by flow cytometric analysis. RESULTS: Women with MPE and SPE had significantly
increased absolute count of CD14(++) CD16(+) HLA-DR(+) monocyte subsets (P < 0.01
each) as compared to NP women. In addition, there were significant differences in
the absolute count of CD14(++) CD16(+) HLA-DR(+) monocyte subsets between MPE and
SPE groups (P < 0.05). The proportion of CD14(++) CD16(+) HLA-DR(+) monocyte
subsets was significantly increased in SPE compared to MPE and NP (P < 0.01
each). The absolute count (r = 0.332, P < 0.05) and proportion (r = 0.447, P <
0.01) of CD14(++) CD16(+) HLA-DR(+) monocytes were positively correlated with the
severity of PE. Multivariate logistic regression analysis further revealed that
the absolute count of CD14(++) CD16(+) HLA-DR(+) monocytes was a potential marker
for PE (P < 0.01). CONCLUSION: A preferential increase in peripheral blood
CD14(++) CD16(+) HLA-DR(+) monocytes is quantitatively correlated with clinical
manifestation of PE.
PMID- 25850578
TI - Negative differential resistance in monolayer WTe2 tunneling transistors.
AB - We report theoretical investigations of quantum transport in monolayer transition
metal dichalcogenide (TMDC) tunneling field effect transistors (TFETs). Due to
the specific electronic structure of TMDC WTe(2), a transmission valley is found
in the conduction band (CB). For a proper choice of the doping, gate and supply
voltages the WTe(2) TFET can produce a giant negative differential resistance
(NDR) with a peak to valley ratio as large as 10(3). The mechanism of NDR is
identified to be due to a transport-mode bottleneck, i.e., the band to band
tunneling from the valence band of the source is partially blocked by a
transmission valley of the CB of the drain. More generally, our calculations show
that electronic structures of at least six TMDC materials possess the
transmission valley.
PMID- 25850576
TI - Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy
enhances real-time in vivo diagnosis of adenomatous polyps during colonoscopy.
AB - Colorectal cancer can be prevented if detected early (e.g., precancerous polyps
adenoma). Endoscopic differential diagnosis of hyperplastic polyps (that have
little or no risk of malignant transformation) and adenomas (that have prominent
malignant latency) remains an unambiguous clinical challenge. Raman spectroscopy
is an optical vibrational technique capable of probing biomolecular changes of
tissue associated with neoplastic transformation. This work aims to apply a fiber
optic simultaneous fingerprint (FP) and high wavenumber (HW) Raman spectroscopy
technique for real-time in vivo assessment of adenomatous polyps during clinical
colonoscopy. We have developed a fiber-optic Raman endoscopic technique capable
of simultaneously acquiring both the FP (i.e., 800-1800 cm(-1)) and HW (i.e.,
2800-3600 cm(-1)) Raman spectra from colorectal tissue subsurface (<200 um) for
real-time assessment of colorectal carcinogenesis. In vivo FP/HW Raman spectra
were acquired from 50 patients with 17 colorectal polyps during clinical
colonoscopy. Prominent Raman spectral differences (p < 0.001) were found between
hyperplastic (n = 118 spectra), adenoma (n = 184 spectra) that could be
attributed to changes in inter- and intra-cellular proteins, lipids, DNA and
water structures and conformations. Simultaneous FP/HW Raman endoscopy provides a
diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating
adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman
technique alone. This study shows that simultaneous FP/HW Raman spectroscopy
technique has the potential to be a clinically powerful tool for improving early
diagnosis of adenomatous polyps in vivo during colonoscopic examination.
PMID- 25850579
TI - Targeting the immune system in head and neck cancer.
PMID- 25850580
TI - Update in germ cell tumours.
AB - PURPOSE OF REVIEW: The purpose of this study is to update the reader on advances
in postpubertal male germ cell tumours (GCTs) over the last 18 months. RECENT
FINDINGS: Single nucleotide polymorphisms, including in four sex-determination
genes, have been identified as additional genetic susceptibility loci to
testicular GCT development. New insights into cisplatin resistance implicate the
PDGFR-PIK3CA-AKT and RAS pathways. Circulating tumour cells and circulating
microRNAs are potential new biomarkers. In clinical stage I (CS-I) GCT, two large
studies have confirmed the excellent outcomes achieved with surveillance, which
is now the management option of choice for CS I-A nonseminoma and all CS-I
seminomas; CS I-B nonseminoma remains controversial. First-line trials of dose
dense multidrug regimens reported promising results but have not yet supplanted
BEPx4. Survivorship issues, including secondary malignancies from chemotherapy,
remain important in this disease and are a continuing focus of ongoing research.
SUMMARY: Important research questions remain across all aspects of GCT. The next
decade is likely to produce many new and exciting discoveries that will benefit
GCT patients.
PMID- 25850582
TI - Gender differences in the association between lifestyle behaviors and diabetes
distress in a community sample of adults with type 2 diabetes.
AB - BACKGROUND: The present study examined the association between moderate and
severe diabetes distress (DD) and lifestyle behaviors (physical activity,
smoking, alcohol consumption) in a community sample of adults with type 2
diabetes mellitus (T2DM). METHODS: A total of 1971 adults with T2DM were
recruited using mixed methods sampling. Participants were considered eligible if
they had a doctor diagnosis of T2DM (<=10 years), were insulin naive, aged 40-75
years, and were from Quebec, Canada. Participants provided information on DD,
lifestyle behaviors, sociodemographic, and diabetes-related factors. Multinomial
logistic regressions examined the association between moderate and severe DD and
each lifestyle behavior, according to gender. Effect estimates can be interpreted
as probability ratios (PR). RESULTS: In females, physical inactivity was
associated with an increased likelihood of moderate distress (PR 2.2; 95%
confidence interval [CI] 1.49-3.24) and severe distress (PR 1.80; 95% CI 1.00
3.24). In males, only severe distress was associated with physical inactivity (PR
1.92; 95% CI 1.00-3.66). Current smoking was associated with a greater
probability of severe distress in males (PR 3.0; 95% CI 1.54-5.84) and females
(PR 1.32; 95% CI 0.67-2.60); however this effect was stronger in males. No
association was found between alcohol consumption and DD in females. In males,
frequent alcohol consumption was associated with a reduced probability of
moderate (PR 0.56; 95% CI 0.34-0.91) and severe distress (PR 0.47; 95% CI 0.21
1.06). CONCLUSIONS: The findings of this study suggest important gender
differences in the association between DD and lifestyle behaviors.
PMID- 25850583
TI - ART for head and neck patients: On the difference between VMAT and IMPT.
AB - Anatomical changes in the head-and-neck (H&N) region during the course of
treatment can cause deteriorated dose distributions. Different replanning
strategies were investigated for volumetric modulated arc therapy (VMAT) and
intensity-modulated proton therapy (IMPT). MATERIAL AND METHODS: For six H&N
patients two repeated computed tomography (CT) and magnetic resonance (MR)
(CT1/MR1 at week 2 and CT2/MR2 at week 4) scans were acquired additionally to the
initial planning CT/MR. Organs-at-risk (OARs) and three targets (CTV70Gy,
CTV63Gy, CTV56Gy) were delineated on MRs and transferred to respective CT data
set. Simultaneously integrated boost plans were created using VMAT (two arcs) and
IMPT (four beams). To assess the need of replanning the initial VMAT and IMPT
plans were recalculated on repeated CTs. Furthermore, VMAT and IMPT plans were
replanned on the repeated CTs. A Demon algorithm was used for deformable
registration of the repeated CTs with the initial CT and utilized for dose
accumulation. Total dose estimations were performed to compare ART versus
standard treatment strategies. RESULTS: Dosimetric evaluation of recalculated
plans on CT1 and CT2 showed increasing OAR doses for both, VMAT and IMPT. The
target coverage of recalculated VMAT plans was considered acceptable in three
cases, while for all IMPT plans it dropped. Adaptation of the treatment reduced
D2% for brainstem by 6.7 Gy for VMAT and by 8 Gy for IMPT, for particular
patients. These D2% reductions were reaching 9 Gy and 14 Gy for the spinal cord.
ART improved target dose homogeneity, especially for protons, i.e. D2% decreased
by up to 8 Gy while D98% increased by 1.2 Gy. CONCLUSION: ART showed benefits for
both modalities. However, as IMPT is more conformal, the magnitude of dosimetric
changes was more pronounced compared to VMAT. Large anatomic variations had a
severe impact on treatment plan quality for both VMAT and IMPT. ART is justified
in those cases irrespective of treatment modalities.
PMID- 25850584
TI - A molecular characterization of the agonist binding site of a nematode cys-loop
GABA receptor.
AB - BACKGROUND AND PURPOSE: Cys-loop GABA receptors represent important targets for
human chemotherapeutics and insecticides and are potential targets for novel
anthelmintics (nematicides). However, compared with insect and mammalian
receptors, little is known regarding the pharmacological characteristics of
nematode Cys-loop GABA receptors. Here we have investigated the agonist binding
site of the Cys-loop GABA receptor UNC-49 (Hco-UNC-49) from the parasitic
nematode Haemonchus contortus. EXPERIMENTAL APPROACH: We used two-electrode
voltage-clamp electrophysiology to measure channel activation by classical GABA
receptor agonists on Hco-UNC-49 expressed in Xenopus laevis oocytes, along with
site-directed mutagenesis and in silico homology modelling. KEY RESULTS: The
sulphonated molecules P4S and taurine had no effect on Hco-UNC-49. Other
classical Cys-loop GABAA receptor agonists tested on the Hco-UNC-49B/C
heteromeric channel had a rank order efficacy of GABA > trans-4-aminocrotonic
acid > isoguvacine > imidazole-4-acetic acid (IMA) > (R)-(-)-4-amino-3
hydroxybutyric acid [R(-)-GABOB] > (S)-(+)-4-amino-3-hydroxybutyric acid [S(+)
GABOB] > guanidinoacetic acid > isonipecotic acid > 5-aminovaleric acid (DAVA)
(partial agonist) > beta-alanine (partial agonist). In silico ligand docking
revealed some variation in binding between agonists. Mutagenesis of a key serine
residue in binding loop C to threonine had minimal effects on GABA and IMA but
significantly increased the maximal response to DAVA and decreased twofold the
EC50 for R(-)- and S(+)-GABOB. CONCLUSIONS AND IMPLICATIONS: The pharmacological
profile of Hco-UNC-49 differed from that of vertebrate Cys-loop GABA receptors
and insect resistance to dieldrin receptors, suggesting differences in the
agonist binding pocket. These findings could be exploited to develop new drugs
that specifically target GABA receptors of parasitic nematodes.
PMID- 25850585
TI - Teaching pediatric and adolescent gynecology.
PMID- 25850586
TI - Applying the one minute preceptor model to pediatric and adolescent gynecology
education.
AB - There are multiple challenges to teaching in the clinical setting. The One Minute
Preceptor is a learner-centered model for effective and efficient teaching in a
clinical setting that can help to overcome these challenges. It consists of 5
microskills: get a commitment; probe for supporting evidence; teach general
rules; reinforce what was right; correct mistakes. This article illustrates with
case vignettes the use of these microskills for the busy Pediatric and Adolescent
Gynecology clinician.
PMID- 25850587
TI - Diagnostic characteristics and metabolic risk factors of cases with polycystic
ovary syndrome during adolescence.
AB - STUDY OBJECTIVE: Polycystic ovary syndrome (PCOS) is a disorder without definite
consensus on its diagnosis and management during adolescence. According to
Amsterdam-2012 consensus, as physiological characteristics of adolescence may
overlap with PCOS signs, it has been indicated that all Rotterdam criteria should
be met. In this present study, characteristics of adolescents with different
phenotypes who were diagnosed with PCOS were evaluated; and presence of
differences for metabolic risk factors between phenotypes were investigated.
DESIGN: The study was performed on adolescent females. According to phenotypic
application models, individuals with all Rotterdam diagnostic criteria
[hyperandrogenism (HA), polycystic ovarian morphology (PCOM), and chronic
anovulation (CA) on the ultrasonography] were in Group 1 (n = 26); with HA and CA
were in Group 2 (n = 10); with HA and PCOM were in Group 3 (n = 7); and with CA
and PCOM were in Group 4 (n = 10). RESULTS: The most common application complaint
(87%) among 53 cases enrolled in the study was menstrual irregularities, and 57%
of cases were not obese. When PCOS was evaluated according to phenotypes, it was
realized that cases that meet all 3 diagnostic Rotterdam criteria according to
the current recommendation in adolescents. (Group 1) was the most common
phenotype. Hyperandrogenism was associated with more metabolic abnormalities.
CONCLUSION: The close monitoring of adolescents, who have 2 diagnostic criteria
is advisable among PCOS phenotypes. Potentially Groups 2 and 3 which have
hyperandrogenism, in particular should warrant closer follow-up although they do
not meet current diagnostic criteria for adolescents.
PMID- 25850588
TI - Perspectives on family planning services among adolescents at a Boston community
health center.
AB - STUDY OBJECTIVE: The aim of this project was to investigate adolescent
perspectives on family planning services at a community-health center, with the
intent to inform health center programs aimed at stemming the adolescent
pregnancy rate. DESIGN: This project was cross-sectional and employed mixed
methods, including surveys and interviews, for the purposes of quality
improvement. SETTING: The project was conducted in the obstetrics and gynecology
clinic at an urban community health center in Boston. PARTICIPANTS: Twenty
adolescent females (age 16-20) who used services at the health center.
INTERVENTION: Participants were individually interviewed to assess perspectives
on family planning services and to identify major influences on methods of
pregnancy prevention. MAIN OUTCOME MEASURE: Major themes were categorized into
contraceptive usage, reproductive health knowledge, adult influence and
communication, barriers to contraceptive care and expectations of a family
planning clinic. RESULTS: All participants were sexually active and 80% had
experienced pregnancy. Reproductive health knowledge was variable and in many
cases limited. Concern about disapproval was a prominent barrier to going to a
clinician for contraception or advice and parents were not often involved in the
initial contraception discussion. Other barriers to use of contraception included
forgetting to use the methods and fear of side effects. CONCLUSION: We identified
several potentially modifiable factors, including lack of knowledge, concern for
provider disapproval and fear of side effects that may limit effective use of
family planning services by adolescents. Further attention should be paid to
these factors in designing and improving youth-friendly services in ob-gyn
clinics.
PMID- 25850589
TI - Breast disorders in girls and adolescents. Is there a need for a specialized
service?
AB - INTRODUCTION: Minor breast concerns in childhood and adolescence are common and
lead to increased anxiety among young patients and their families, particularly
due to high correlation with breast cancer. However, most breast services aim at
managing adults and triaging patients with breast cancer, whereas adolescent
medicine specialists or pediatricians are usually not appropriately trained to
identify and treat breast pathology. METHODS: We reviewed hospital records of all
patients attending a pediatric and adolescent gynecology or breast clinic of a
tertiary referral hospital, with a breast related symptom, between January 2009
and December 2011. We collected information regarding age at presentation, age at
menarche, diagnosis, management and outcome. RESULTS: We identified 81 patients
of which 11 presented with an abnormal nipple or areolar secretion, 33 had a
palpable lump, 20 had mastitis, and 16 had unequal breast development. One
patient presented with virginal breast hypertrophy. Three out of 11 of the
patients with an abnormal secretion had a cyst identified on ultrasonography. Out
of the palpable lumps 12 were fibroadenomas, 3 were phyllodes tumors, and 14 were
cystic in nature. The phyllodes tumors and half of the fibroadenomas were
removed. The remaining fibroadenomas remain under regular ultrasonographic follow
up. All cases of mastitis were treated conservatively and resolved with broad
spectrum antibiotic treatment. CONCLUSION: In our series, no malignancies were
identified. Although 8 patients required surgical treatment, the majority of
cases were treated conservatively.
PMID- 25850591
TI - Body image in adolescent pregnancy.
AB - STUDY OBJECTIVES: To review the existing literature on body image in adolescent
pregnancy and explore concepts about the relationship between the two. DESIGN: A
systematic review. SETTING: Peer-reviewed articles were identified through
MEDLINE (1946-present) and PsycINFO (1806-November 2013), conducted in any
setting. PARTICIPANTS: Pregnant and postpartum adolescents ages 13-19 y.
INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): The outcome measures used in the
studies reviewed varied: themes from focus groups, diary entry analysis,
Pregnancy and weight gain attitude scale, Edinburgh postnatal depression scale,
Parenting stress index, Eating disorder inventory, Tennessee self concept scale.
RESULTS: The search yielded a total of 149 studies, of which 6 were relevant to
the specific topic and age group. The very limited research shows a dichotomy in
body image perception during pregnancy in adolescence; some studies show an
increase in body image disturbance and dissatisfaction during pregnancy in
adolescents, and other studies reviewed found that the majority of pregnant
adolescents had positive body image and positive attitudes towards weight gain. A
bidirectional link between depression and negative body image in adolescent
pregnancy is suggested. CONCLUSIONS: The current research exploring the
relationshp between body image and pregnancy in adolescence is limited, both in
quality and quantity. Future research is needed to evaluate longitudinal models
that will better inform about potential risk factors for body dissatisfaction
during pregnancy in adolescence, including the possible role of depression.
PMID- 25850590
TI - Evidence to incorporate inclusive reproductive health measures in guidelines for
childhood and adolescent cancer survivors.
AB - OBJECTIVE: Female childhood cancer survivors are at an increased risk of
reproductive health impairment. We compared reproductive health outcomes with the
recommended standard in a cohort of childhood cancer survivors. STUDY DESIGN AND
PARTICIPANTS: A retrospective chart review of 222 female childhood cancer
survivors aged 21 years or younger that presented to a tertiary referral center
between 1997-2008 was initiated. The main outcome measures were the compliance
with the American Society of Clinical Oncology guidelines for childhood cancer
survivor management of reproductive health. In particular, we evaluated menstrual
cycle regularity, fertility preservation counseling, and endocrine profile, as
defined by follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH)
levels as surrogate markers for ovarian reserve. Secondary outcomes were to study
the contribution of survivor clinics in enforcing these guidelines. RESULTS: Of
136 patients older than 13 years at their last visit, 58 patients (43%) had FSH
data available and none had AMH data. Patients were stratified into 3 groups
according to FSH levels. Forty of 58 patients (69%) have normal ovarian reserve
(FSH level < 10), 10 of 58 patients (17%) have decreased ovarian reserve (FSH
levels 10-40), and 8 of 58 patients (14%) have premature menopause, defined as
FSH > 40. Most patients with amenorrhea have elevated FSH levels indicating
primary ovarian insufficiency, while 3 patients (2.2%) have low FSH levels
consistent with hypothalamic amenorrhea. None of the patients were counseled on
fertility preservation. CONCLUSIONS: Reproductive health follow-up in children
with cancer, including FSH and AMH measurement when indicated, should be
established and strictly adhered.
PMID- 25850592
TI - Labial adhesions and outcomes of office management.
AB - STUDY OBJECTIVE: To evaluate clinical outcomes of labial adhesions (LA) and to
examine the association between LA, lichen sclerosus (LS), eczema (ECZ), or
asthma. DESIGN: Retrospective study. SETTING: Single pediatric and adolescent
gynecology clinic, Houston, Texas. PARTICIPANTS: 50 girls diagnosed with LA from
2006-2011. INTERVENTIONS AND MAIN OUTCOME MEASURES: Resolution, recurrence,
single vs multiple treatments, need for surgery, and conditions such as LS, ECZ,
and asthma were reviewed. RESULTS: Mean age was 19.6 months (range 0-84 months),
and 48% were Caucasian. Most patients were symptomatic (62%) and all 50 patients
chose estrogen treatment. The majority (74%) required multiple treatments, as
opposed to a single treatment (26%). Patients with multiple treatments were more
likely to be severely agglutinated (P = .05) and to need manual separation after
failed topical treatment (P = .08). The prevalence of asthma, LS, and ECZ was
9.8%, 7.8%, and 3.9% respectively. There was no association between LS, ECZ, or
asthma, and number of treatments. Both asthma (N = 3; 8%), and LS (N = 2; 5%)
were present among the severe agglutinated group; however, this difference was
not statistically significant (P values .59 and .99). No association with ECZ was
seen in either group. CONCLUSION: Severe agglutination tends to be associated
with need of multiple treatments and manual separation. A concurrent diagnosis of
LS, ECZ, or asthma was not associated with number of treatments but there appears
to be a trend towards severity of LA in patients with asthma and LS.
PMID- 25850593
TI - The effect of chromium supplementation on polycystic ovary syndrome in
adolescents.
AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition. Treatment
with chromium has been shown to improve insulin sensitivity in adults with PCOS.
Treatment of adolescents with PCOS remains a challenge. OBJECTIVE: To investigate
the effect of chromium supplementation on the various components of polycystic
ovary syndrome in adolescent girls. PATIENTS AND METHODS: Thirty-five adolescent
girls with PCOS were enrolled. History of menstrual irregularities was recorded.
All underwent physical examination for presence of acne, scoring of hirsutism,
and calculation of body mass index. Pelvic ultrasonography was done and serum
free testosterone was measured in all subjects. All subjects received 1000 MUg
chromium picolinate for 6 months followed by re-evaluation. RESULTS: Mean (SD)
age was 15.5 (1) years (range: 14-17 y). No significant change in BMI standard
deviation score (SDS) with chromium supplementation was noted (1.9 (0.7) SDS vs 2
(0.7) SDS, P = .638). The number of patients with oligo/amenorrhea decreased with
treatment (29/35 (83%) versus 11/35 (31%), P < .001). Significant reduction in
mean ovarian volume (P < .001), total follicular count (P < .034), and free
testosterone (P< .002) was observed. No significant improvement in acne or
hirsutim was noted. CONCLUSION: Supplementation with chromium to adolescents with
PCOS is a promising treatment option.
PMID- 25850594
TI - Infertility and the presence of insulin resistance are associated with increased
oxidative stress in young, non-obese Turkish women with polycystic ovary
syndrome.
AB - STUDY OBJECTIVE: To investigate the relationship between both insulin resistance
and fertility and the oxidant/antioxidant system in young, non-obese patients
diagnosed with polycystic ovary syndrome (PCOS). DESIGN: Case-control study.
SETTING: Department of Obstetrics and Gynecology, Ege University, Izmir, Turkey.
PARTICIPANTS: PCOS patients without insulin resistance (IR-) (n = 33), PCOS
patients with insulin resistance (IR+) (n = 27), and healthy controls (n = 30).
Patients with PCOS and regular sexual intercourse were further divided into
infertile (n = 14) and fertile (n = 15) groups. MAIN OUTCOME MEASURES: The
malondialdehyde (MDA) and thiol levels as well as the catalase (CAT) and
superoxide dismutase (SOD) enzyme activities. RESULTS: Both IR+ and IR- PCOS
patients had higher MDA levels and lower thiol levels when compared to the
controls (each P < .001). However, only IR- patients had significantly higher SOD
(3700.81 +/- 410.13 vs 2614.19 +/- 611.80 U/g Hb; P < .001) and CAT (7565.06 +/-
628.27 vs 6819.61 +/- 539.2 U/g Hb; P < .001) activities when compared to the
controls. Infertile PCOS patients had significantly higher MDA levels (347.5 +/-
22.8 vs 278.6 +/- 42.6 nmol/g Hb, P < .001) and lower thiol levels (498.5 +/-
56.2 vs 568.5 +/- 38.6 MUmol/l, P = .001) when compared to fertile patients.
CONCLUSIONS: The results of this study demonstrated an imbalance in the oxidative
antioxidative system of PCOS patients. This imbalance was worse in IR+ and
infertile PCOS patients.
PMID- 25850595
TI - Working with the Food and Drug Administration's Center for Devices to Advance
Regulatory Science and Medical Device Innovation.
PMID- 25850597
TI - Highly Efficient Ruthenium-Catalyzed N-Formylation of Amines with H2 and CO2.
AB - A highly efficient catalyst system based on ruthenium-pincer-type complexes has
been discovered for N-formylation of various amines with CO2 and H2, thus
affording the corresponding formamides with excellent productivity (turnover
numbers of up to 1,940,000 in a single batch) and selectivity. Using a simple
catalyst recycling protocol, the catalyst was reused for 12 runs in N,N
dimethylformamide production without significant loss of activity, thus
demonstrating the potential for practical utilization of this cost-effective
process. A one-pot two-step procedure for hydrogenation of CO2 to methanol via
the intermediacy of formamide formation has also been developed.
PMID- 25850598
TI - Long-term Auditory Symptoms in Patients With Sporadic Vestibular Schwannoma: An
International Cross-Sectional Study.
AB - BACKGROUND: There are limited data on the long-term auditory symptoms in patients
with sporadic small- and medium-sized vestibular schwannoma (VS). The initial
treatment strategy for VS is controversial. OBJECTIVE: To characterize auditory
symptoms in a large cohort of patients with VS. METHODS: Patients with <=3 cm VS
who underwent primary microsurgery, gamma knife surgery, or observation between
1998 and 2008 at 2 independent hospitals were identified. Clinical data were
extracted from existing VS databases. At a mean time of 7.7 years after initial
treatment, patients were surveyed via mail with the use of the Hearing Handicap
Inventory for Adults (HHIA) and the Tinnitus Handicap Inventory. RESULTS: The
response rate was 79%; a total of 539 respondents were analyzed. Overall, the
hearing prognosis was poor, because more than 75% of all patients had
nonserviceable hearing at the last clinical follow-up. Good baseline hearing
proved to be a strong predictor for maintained serviceable hearing. Treatment
modality was independently associated with both audiometric outcome and HHIA
results. Active treatment with microsurgery or gamma knife surgery did not appear
to be protective, because patients who were observed had the greatest probability
of durable hearing. Patients in the surgical series had the greatest hearing
loss. Tinnitus Handicap Inventory results were less predictable. The only
predictors of tinnitus handicap were age and HHIA score. CONCLUSION: The overall
prognosis for hearing in sporadic VS is poor regardless of treatment strategy.
Treatment modality was an independent predictor of hearing status; observation
was associated with the highest rate of hearing preservation. .
PMID- 25850599
TI - The effects of anatomic variations on stereotactic laser amygdalohippocampectomy
and a proposed protocol for trajectory planning.
AB - BACKGROUND: Stereotactic laser amygdalohippocampectomy (SLAH) is a promising
minimally invasive alternative for mesial temporal lobe epilepsy. As seizure
outcome has been associated with the extent of amygdalar and hippocampal
ablation, it is important to select a safe trajectory optimizing involvement of
both structures; however, variations in temporal anatomy significantly affect the
overall complexity of planning. OBJECTIVE: To quantify anatomic variables of SLAH
and facilitate stereotactic planning by developing a protocol for optimally
targeting the amygdalohippocampal complex (AHC). METHODS: We performed a
retrospective analysis of 19 SLAHs. Anatomic measurements from preoperative
magnetic resonance imaging and laser trajectory measurements from coregistered
postoperative magnetic resonance imaging were taken in 11 patients. Simple linear
regression analysis was performed to identify significant predictor variables
determining ablation extent. Based on these data, a protocol for optimal
trajectory planning was developed and subsequently implemented in 8 patients.
RESULTS: The medial angle of the laser trajectory correlated with the medial
angle of the AHC. The length of amygdalar cannulation was predictive of its
ablation volume. All trajectories passed through a posteroinferior corridor
formed by the lateral ventricle superiorly and collateral sulcus inferiorly. Our
protocol facilitated planning and increased the volume of AHC ablation.
CONCLUSION: The medial AHC angle dictates the medial trajectory angle and a path
from the posteroinferior corridor through the hippocampus and the center of the
amygdala dictates the caudal angle. These observations led to a protocol for long
axis AHC cannulation that maintains an extraventricular trajectory to minimize
hemorrhage risk and targets the center of the amygdala to optimize ablation
volumes.
PMID- 25850600
TI - The Mechanism of Ligamentum Flavum Hypertrophy: Introducing Angiogenesis as a
Critical Link That Couples Mechanical Stress and Hypertrophy.
AB - BACKGROUND: Biochemical alterations associated with mechanical stress have been
explored as an initiating step in the pathological progression of ligamentum
flavum hypertrophy (LFH); however, this mechanism remains poorly understood.
Recently, the inflammation induced after mechanical stress and the subsequent
response of ligamentum flavum (LF) cells have been implicated in LFH pathology.
OBJECTIVE: To investigate the hypothesis that angiogenesis may be a critical link
between hypertrophy and a series of stimulating events, including mechanical
stress. METHODS: LF from 20 lumbar spinal canal stenosis (LSCS) patients and 16
non-LSCS patients (control group) were collected during surgery. Patient
demographic and radiographic data were obtained. The levels of angiogenic factors
(vascular endothelial growth factor [VEGF], angiopoietin-1, vascular cell
adhesion molecule, and basic fibroblast growth factor) in the LF were
investigated by using an enzyme-linked immunosorbent assay. Angiogenesis was also
quantified by immunohistochemical detection of CD34-positive capillaries. The
correlations among clinical factors, including radiographic factors, angiogenic
factors, and angiogenesis, were statistically analyzed. RESULTS: The LSCS group
was older and exhibited a longer symptom duration, wider segmental motion, and
thicker LF than the control group. The LSCS group showed significantly higher
tissue concentrations of VEGF (P < .001) that positively correlated with LF
thickness (r = 0.557, P < .001) and segmental motion (r = 0.586, P < .001). The
LSCS group showed significantly more CD34-positive capillaries than the control
group (P = .004). CONCLUSION: The LSCS group showed greater segmental motion,
higher VEGF concentrations, and more CD34-positive capillaries than the control
group. These data indicate that VEGF-mediated angiogenesis following mechanical
stress may be a critical step within the series of pathological events in LFH.
PMID- 25850601
TI - Outcomes in Reoperated Low-Grade Gliomas.
AB - BACKGROUND: Low-grade gliomas (LGGs) comprise a diverse set of intrinsic brain
tumors that correlate strongly with survival. Data on the effect of reoperation
are sparse. OBJECTIVE: To evaluate the effect of reoperation on patients with
LGG. METHODS: Fifty-two consecutive patients with reoperated LGGs treated at the
University of Washington between 1986 and 2004 were identified and evaluated in a
retrospective analysis. RESULTS: The average overall survival (OS) for this
cohort was 12.95 +/- 0.96 years. The overall 10-year survival rate was 57%. The
absence of any residual tumor at either the first or second operation was
associated with significantly increased OS. Negative prognostic variables for OS
included the use of upfront radiation and pathology at recurrence. The average
overall progression-free survival to the first recurrence (PFS1) was 6.23 +/-
0.51 years. Positive prognostic factors for improved PFS1 included the use of
upfront radiation therapy. Variables not associated with differences in PFS1
included the use of upfront chemotherapy, enhancement, pathology, extent of
resection, the presence of residual tumor, and Karnofsky Performance Scale score
<80. The average overall progression-free survival to the second recurrence was
2.73 +/- 0.39 years. Pathology at recurrence was associated with significant
differences in progression-free survival to the second recurrence, as was extent
of resection at time of first recurrence, and Karnofsky Performance Scale score
<80. CONCLUSION: This is among the largest studies to assess variables associated
with outcome in patients with reoperated LGG. Reresection appears to provide
significant benefit, and extent of resection remains the strongest predictor of
OS.
PMID- 25850602
TI - An Unusual Case of Constitutional Mismatch Repair Deficiency Syndrome With
Anaplastic Ganglioglioma, Colonic Adenocarcinoma, Osteosarcoma, Acute Myeloid
Leukemia, and Signs of Neurofibromatosis Type 1: Case Report.
AB - BACKGROUND AND IMPORTANCE: Constitutional mismatch repair deficiency (CMMRD)
syndrome is a disorder with recessive inheritance caused by biallelic mismatch
repair gene mutations, in which mismatch repair defects are inherited from both
parents. This syndrome is associated with multiple cancers occurring in
childhood. The most common tumors observed with CMMRD include brain tumors,
digestive tract tumors, and hematological malignancies. The aim of this study was
to report new phenotypic expressions of CMMRD syndrome and add new insight to the
existing knowledge about this disease. A review of the literature was conducted
and recommendation for surveillance and follow-up in patients with CMMRD are
proposed. CLINICAL PRESENTATION: We report for the first time in the literature,
the case of a 22-year-old female patient who was diagnosed with CMMRD syndrome,
with the development of 2 unusual tumors: an anaplastic ganglioglioma and an
osteosarcoma. She presented initially with an anaplastic ganglioglioma and later
developed several malignancies including colonic adenocarcinoma, osteosarcoma,
and acute myeloid leukemia. The patient had an atypical course of her disease
with development of the initial malignancy at an older age and a remarkably long
survival period despite developing aggressive tumors. CONCLUSION: Many aspects of
this disease are still unknown. We identified a case of CMMRD in a patient
presenting with an anaplastic ganglioglioma, who underwent successful surgical
resection, chemotherapy, and radiotherapy and has had one of the longest survival
periods known with this disease. This case broadens the tumor spectrum observed
with CMMRD syndrome with anaplastic ganglioglioma and osteosarcoma as new
phenotypic expressions of this genetic defect.
PMID- 25850603
TI - Validation of a System to Predict Recanalization After Endovascular Treatment of
Intracranial Aneurysms.
AB - BACKGROUND: With increasing use of endovascular techniques in the treatment of
ruptured and unruptured aneurysms, the issue of obliteration efficacy has become
increasingly important. We have previously reported the Aneurysm Recanalization
Stratification Scale, which uses accessible predictors including aneurysm
specific factors (size, rupture, and intraluminal thrombosis) and treatment
related features (treatment modality and immediate angiographic result) to
predict retreatment risk after endovascular therapy. OBJECTIVE: To assess the
external validity of the Aneurysm Recanalization Stratification Scale. METHODS:
External validity was assessed in independent cohorts from 4 centers in the
United States and Canada where endovascular and open neurovascular procedures are
performed, and in a multicenter cohort of 1543 patients. Probability of
retreatment stratified by risk score was derived for each center and the combined
multicenter cohort. RESULTS: Despite moderate variability in retreatment rate
among centers (29.5%, 9.9%, 9.6%, 26.3%, 19.7%, and 18.3%), the Aneurysm
Recanalization Stratification Scale demonstrated good predictive value with C
statistics of 0.799, 0.943, 0.780, 0.695, 0.755, and 0.719 for each center and
the combined cohort, respectively. Probability of retreatment stratified by risk
score for the combined cohort is as follows: -2, 4.9%; -1, 5.7%; 0, 5.8%; 1,
13.1%; 2, 19.2%; 3, 34.9%; 4, 32.7%; 5, 73.2%; 6, 89.5%; and 7, 100.0%.
CONCLUSION: Surgical decision-making and patient-centered informed consent
require comprehensive and accessible information on treatment efficacy. The
Aneurysm Recanalization Stratification Scale is a valid prognostic index. This is
the first comprehensive model that has been developed to quantitatively predict
retreatment risk following endovascular therapy.
PMID- 25850604
TI - Exploring the relationship between client perspectives, clinical expertise and
research evidence.
AB - PURPOSE: This paper examines the relationship between components of evidence
based practice (clinical expertise, patient perspective and research evidence).
METHOD: Findings are examined from two research programs: the Better
Communication Research Program and Child Talk, including exploratory studies of
the views of parents and children regarding speech-language pathology and studies
of current practice by SLPs in England. Systematic reviews of the research
literature were also undertaken. The paper analyses relationships between
outcomes valued by children and parents and those reported in the literature and
in practice, parents' perspectives regarding intervention in comparison with
clinicians' reports of practice and the extent to which research evidence
underpins current practice is examined. RESULT: Parents and children value
functional outcomes and positive experiences; these are not routinely measured in
research or practice. Therapy is perceived positively by most parents; however,
some are ambivalent and less clear about the rationale. Commonly used
interventions are supported by evidence, but there are gaps regarding some
critical therapy components. CONCLUSION: The paper discusses four challenges to
evidence-based practice: the consistency and clarity of descriptions of
interventions; consensus based models of practice; understanding of the
mechanisms of change; and, finally, the operationalization of client preferences
within an evidence-based practice framework.
PMID- 25850605
TI - Implementation and Operational Research: Integration of Family Planning Services
in a Peer-Managed HIV Care Clinic Serving Most-at-Risk Populations in Phnom Penh,
Cambodia.
AB - OBJECTIVE: To assess contraceptive uptake and method choice among women living
with HIV (WLHIV) attending an HIV care clinic serving most-at-risk women in Phnom
Penh, Cambodia, before and after the implementation of family planning (FP)
services. METHODS: Semistructured questionnaires were administered to clients
before (July, 2011) and after (July, 2012) FP service implementation with
provision of contraceptive methods (pills, injectables, implants, and
intrauterine device [IUD]). RESULTS: Among 250 and 249 clients interviewed before
and after implementation respectively, 24.5% of women reported selling sex for
money during the last 6 months before and 35.3% after implementation. Awareness
about contraceptive methods significantly increased among clients
postimplementation. Among sexually active women, male condom remained the
contraceptive method of choice with an overall condom use during the last 6
months at 91% postimplementation vs. 95.6% preimplementation (P = 0.11). Although
the use of noncondom FP methods increased but not significantly (16.4% after vs.
12.6% before implementation, P = 0.8), the use of dual method (condom plus
another method) remained low and did not significantly increase after
implementation (14.8% after vs. 11.0% before, P = 0.28). CONCLUSIONS: Our results
show that FP practices of WLHIV attending an HIV care clinic for most-at-risk
populations did not significantly change after integration on-site provision of a
wide range of FP methods. Innovative strategies and further research are needed
to better understand how to promote the use of noncondom FP methods and prevent
unwanted pregnancies and abortions among most-at-risk women and WLHIV.
PMID- 25850608
TI - Differences in the treatment and evolution of acute coronary syndromes according
to gender: what are the causes?
AB - AIMS AND OBJECTIVES: The objectives of this study were to analyse the differences
in the treatment and the evolution of acute coronary syndromes according to the
gender of the patient and to determine the likely causes of these differences.
BACKGROUND: Epidemiological studies confirm the differences in the course and
treatment of acute coronary syndromes according to factors such as gender and
age. The factors associated with the observed gender-based differences are not
known. DESIGN AND METHODS: This prospective study was conducted on 596 patients
treated in the Hospital Emergency Service of the Hospital Complex of Navarra,
Spain, from 1 January 2012 to April 2013 with acute coronary syndromes. A
bivariate and logistic analysis has been made by adjusting the age and severity
of process to know the differences by gender. RESULTS: A total of 71.8% (n = 428)
were men, and the remaining 28.2% (168) were women. The mean age of the men was
66.4 +/- 12.7 years, and the mean age of the women was 72.5 +/- 13.9 years. We
found that antiplatelet drugs (68.4 vs. 22.7%), blockers (70 vs. 25.4%), ACE
inhibitors (56.2 vs. 15.6%), fibrinolysis (17.2 vs. 4.5%, p = 0.025) and primary
angioplasty (AP) (38.7 vs. 16.3%, p = 0.008) were less frequently administered to
women compared with men. We observed an additional delay in the demand for health
care in women with acute coronary syndromes compared with men. CONCLUSIONS: There
is an association between treatment differences and gender. The delay in the
request of health care in women is observed to be the largest correlating factor,
in addition to voluntary discharge in women affected by acute coronary syndromes.
RELEVANCE TO CLINICAL PRACTICE: Delays in seeking medical care or voluntary
discharge are likely factors related to worse outcomes in women. These factors
should be explored, and the results should be made available to the public,
particularly to women.
PMID- 25850607
TI - Comparative Safety and Neuropsychiatric Adverse Events Associated With Efavirenz
Use in First-Line Antiretroviral Therapy: A Systematic Review and Meta-Analysis
of Randomized Trials.
AB - INTRODUCTION: Efavirenz (EFV) is widely used for the treatment of antiretroviral
naive HIV-positive individuals, but there are concerns about the risk of adverse
neuropsychiatric events. We systematically reviewed the safety of EFV in first
line therapy. METHODS: Four databases were searched until October 2014 for
randomized trials comparing EFV against non-EFV-based regimens for the treatment
of antiretroviral-naive HIV-positive adults and children. The primary outcome was
drug discontinuation as a result of any adverse event. Relative risks and
proportions were pooled using random-effects meta-analysis. RESULTS: Forty-two
trials were included for review. A lower relative and absolute risk of
discontinuations due to adverse drug reactions was seen with EFV compared to
nevirapine. The relative and absolute risk of discontinuation was greater for EFV
compared with low-dose EFV, rilpivirine, tenofovir, atazanavir, and maraviroc.
The relative risk of discontinuation was greater for EFV compared with
dolutegravir and raltegravir, but absolute risks were not significantly
different. There was no difference in the risk of any severe clinical adverse
events for any comparison. With the exception of dizziness, fewer than 10% of
patients exposed to EFV experienced any other specific type of neuropsychiatric
event. No suicides were reported. CONCLUSIONS: This review found that over 90% of
patients remained on an EFV-based first-line regimen after an average follow-up
time of 78 weeks. The relative risk of discontinuations due to adverse events was
higher for EFV compared with most other first-line options, but absolute
differences were less than 5% for all comparisons.
PMID- 25850609
TI - Endocrine pregnancy monitoring in the two-toed sloth (Choloepus didactylus):
"Pregnant or not pregnant".
AB - Progesterone (P4), pregnanediol glucuronide (PdG), estradiol-17beta (E2), and
estrone sulfate (E1S) were measured in the feces of four female two-toed sloths
(Choloepus didactylus) for early pregnancy diagnosis. For individual feces
assignment, the examined female sloths were fed with a turquoise food colorant
every second day. Fecal samples were collected one to four times per week,
depending on the defecation rate throughout the pregnancies and the postpartum
periods. The complete course of pregnancy was subdivided into three 16-week
intervals (trimester of pregnancy, TP1-3) and a 5-week post-partum period after
birth. Progesterone and PdG concentrations started to increase above luteal phase
levels 3 weeks after conception (P = 0.028 and 0.005, respectively). At the
beginning of TP1, P4 concentrations averaged 345.0 +/- 283.0 ng/g and increased
approximately 100- to 300-fold to a peak of 7588.0 +/- 6717.0 ng/g over the TP3.
Progesterone concentrations were considerably lower than PdG concentrations that
started with 3206.0 +/- 1500.0 ng/g at TP1 and increased up to 12.8556.0 +/-
53.744.0 ng/g until birth. In contrast, mean concentrations of E2 (8.2 +/- 2.4
11.7 +/- 4.2 ng/g) and E1S (12.2 +/- 6.7-22.9 +/- 13.0 ng/g) elevated
insignificantly and were not suitable for pregnancy detection. All hormones
analyzed decreased rapidly within the first weeks after birth. Progesterone and
PdG, as well as E2 and E1S, highly significantly correlated (r = 0.602, P < 0.001
and r = 0.497, P < 0.001, respectively) at TP1. During the TP2, only P4 and PdG
significantly correlated (TP2: r = 0.661, P < 0.001 and postpartum period: r =
0.616, P = 0.009). In summary, only P4 metabolite concentrations were suitable to
determine the status of reproduction in the two-toed sloth. Thereby, PdG was
ideally suited to diagnose early pregnancy because it was more sensitive and
detected pregnancy 2 weeks earlier than P4.
PMID- 25850610
TI - Occurrence of bacteria and polymorphonuclear leukocytes in fetal compartments at
parturition; relationships with foal and mare health in the peripartum period.
AB - This study investigated the relationship of the health of the newborn foal and
(1) number of polymorphonuclear leukocytes (PMNLs) in the amniotic fluid, (2)
bacteria present in the amniotic fluid and the venous umbilical blood, and (3)
bacteria present in the uterus of the newly foaled mare. A further aim was to
investigate relationships between the bacteriologic findings in the amniotic
fluid, umbilical blood, and uterus postpartum. Samples were taken from 50
Standardbred trotter foaling mares from a well-managed stud in Sweden.
Parturition was spontaneous in all cases. Length of pregnancy, parturition and
postpartum complications, health status of the foal, the time between foaling and
the expulsion of the placenta, and the number of postfoaling mares becoming
pregnant after insemination were recorded. Amniotic fluid was collected when the
amniotic vesicle was clearly visible; it was analyzed for bacteriology and
occurrence of PMNLs. Umbilical blood was analyzed for the presence of bacteria
and the concentration of serum amyloid A. The uterus of the mare was swabbed for
bacteriology 6 to 17 hours postpartum. A blood sample was taken from the foal
before administering plasma. The foals were divided into two groups: group 1
required up to 2 hours to rise after birth (<=2 hours; 31 foals) and group 2
required more than two hours (>2 hours; 19 foals). The length of gestation varied
between 332 and 356 days; there was no significant difference in gestation length
between the two foal groups. Partus and postpartum complications occurred in a
significantly higher proportion of mares giving birth to group 2 foals than group
1 foals (P = 0.02), although uterine culture postpartum and the subsequent
pregnancy rate per season were not different between the groups. Compromised
health status was significantly higher among foals belonging to group 2 than
group 1 (P = 0.001). Most of the amniotic samples contained 5% or less PMNLs.
Only three samples contained more than 30% PMNLs; group 2 foals had the highest
percentage of PMNLs. Bacterial growth was found in both amniotic fluid (57%) and
umbilical blood (35%) in mares irrespective of whether their foals were healthy
or compromised. Coagulase-negative staphylococci were the most frequent bacteria.
There were no differences in bacterial occurrence in amniotic fluid or in
umbilical blood between the two foal groups.
PMID- 25850606
TI - Implementation and Operational Research: Effects of CD4 Monitoring Frequency on
Clinical End Points in Clinically Stable HIV-Infected Patients With Viral
Suppression.
AB - BACKGROUND: Current treatment guidelines for HIV infection recommend routine CD4
lymphocyte (CD4) count monitoring in patients with viral suppression. This may
have a limited impact on influencing care as clinically meaningful CD4 decline
rarely occurs during viral suppression. METHODS: In a regional HIV observational
cohort in the Asia-Pacific region, patients with viral suppression (2 consecutive
viral loads <400 copies/mL) and a CD4 count >=200 cells per microliter who had
CD4 testing 6 monthly were analyzed. Main study end points were occurrence of 1
CD4 count <200 cells per microliter (single CD4 <200) and 2 CD4 counts <200 cells
per microliter within a 6-month period (confirmed CD4 <200). A comparison of time
with single and confirmed CD4 <200 with biannual or annual CD4 assessment was
performed by generating a hypothetical group comprising the same patients with
annual CD4 testing by removing every second CD4 count. RESULTS: Among 1538
patients, the rate of single CD4 <200 was 3.45/100 patient-years and of confirmed
CD4 <200 was 0.77/100 patient-years. During 5 years of viral suppression,
patients with baseline CD4 200-249 cells per microliter were significantly more
likely to experience confirmed CD4 <200 compared with patients with higher
baseline CD4 [hazard ratio, 55.47 (95% confidence interval: 7.36 to 418.20), P <
0.001 versus baseline CD4 >=500 cells/MUL]. Cumulative probabilities of confirmed
CD4 <200 was also higher in patients with baseline CD4 200-249 cells per
microliter compared with patients with higher baseline CD4. There was no
significant difference in time to confirmed CD4 <200 between biannual and annual
CD4 measurement (P = 0.336). CONCLUSIONS: Annual CD4 monitoring in virally
suppressed HIV patients with a baseline CD4 >=250 cells per microliter may be
sufficient for clinical management.
PMID- 25850611
TI - Battles and hijacks: noncoding transcription in plants.
AB - Noncoding RNAs have emerged as major components of the eukaryotic transcriptome.
Genome-wide analyses revealed the existence of thousands of long noncoding RNAs
(lncRNAs) in several plant species. Plant lncRNAs are transcribed by the plant
specific RNA polymerases Pol IV and Pol V, leading to transcriptional gene
silencing, as well as by Pol II. They are involved in a wide range of regulatory
mechanisms impacting on gene expression, including chromatin remodeling,
modulation of alternative splicing, fine-tuning of miRNA activity, and the
control of mRNA translation or accumulation. Recently, dual noncoding
transcription by alternative RNA polymerases was implicated in epigenetic and
chromatin conformation dynamics. This review integrates the current knowledge on
the regulatory mechanisms acting through plant noncoding transcription.
PMID- 25850612
TI - My body aches.
PMID- 25850613
TI - Mitochondria in autoinflammation: cause, mediator or bystander?
AB - People suffering from autoinflammatory disease (AID) have recurring sterile
inflammation due to dysregulated inflammasome activation. Although certain genes
have been associated with several AIDs, the molecular underpinnings of seemingly
spontaneous inflammation are not well understood. Emerging data now suggest that
mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA), and
autophagy might drive key signaling pathways towards activation of the
inflammasome. In this review, we discuss recent findings and highlight common
features between different AIDs and mitochondrial (dys)function. Although it is
still early to identify clear therapeutic targets, the emerging paradigms in
inflammation and mitochondrial biology show that mitochondria play an important
role in AIDs, and understanding this interplay will be key in the development of
new therapies.
PMID- 25850614
TI - Application of science-based restoration planning to a desert river system.
AB - Persistence of many desert river species is threatened by a suite of impacts
linked to water infrastructure projects that provide human water security where
water is scarce. Many desert rivers have undergone regime shifts from spatially
and temporally dynamic ecosystems to more stable systems dominated by homogenous
physical habitat. Restoration of desert river systems could aid in biodiversity
conservation, but poses formidable challenges due to multiple threats and the
infeasibility of recovery to pre-development conditions. The challenges faced in
restoring desert rivers can be addressed by incorporating scientific
recommendations into restoration planning efforts at multiple stages, as
demonstrated here through an example restoration project. In particular, use of a
watershed-scale planning process can identify data gaps and irreversible
constraints, which aid in developing achievable restoration goals and objectives.
Site-prioritization focuses limited the resources for restoration on areas with
the greatest potential to improve populations of target organisms. Investment in
research to understand causes of degradation, coupled with adoption of a guiding
vision is critical for identifying feasible restoration actions that can enhance
river processes. Setting monitoring as a project goal, developing hypotheses for
expected outcomes, and implementing restoration as an experimental design will
facilitate adaptive management and learning from project implementation.
Involvement of scientists and managers during all planning stages is critical for
developing process-based restoration actions and an implementation plan to
maximize learning. The planning process developed here provides a roadmap for use
of scientific recommendations in future efforts to recover dynamic processes in
imperiled riverine ecosystems.
PMID- 25850615
TI - Do global indicators of protected area management effectiveness make sense? A
case study from Siberia.
AB - Driven by the underperformance of many protected areas (PAs), protected area
management effectiveness (PAME) evaluations are increasingly being conducted to
assess PAs in meeting specified objectives. A number of PAME tools have been
developed, many of which are based on the IUCN-WCPA framework constituting six
evaluative elements (context, planning, input, process, output, and outcomes). In
a quest for a more universal tool and using this framework, Leverington et al.
(Environ Manag 46(5):685-698, 2010) developed a common scale and list of 33
headline indicators, purported to be representative across a wide range of
management effectiveness evaluation tools. The usefulness of such composite tools
and the relative weighting of indicators are still being debated. Here, we
utilize these headline indicators as a benchmark to assess PAME in 37 PAs of four
types in Krasnoyarsk Kray, Russia, and compare these with global results.
Moreover, we review the usefulness of these indicators in the Krasnoyarsk context
based on the opinions of local PA management teams. Overall, uncorrected
management scores for studied PAs were slightly better (mean = 5.66 +/- 0.875)
than the global average, with output and outcome elements being strongest, and
planning and process scores lower. Score variability is influenced by PA size,
location, and type. When scores were corrected based on indicator importance, the
mean score significantly increased to 5.75 +/- 0.858. We emphasize idiosyncrasies
of Russian PA management, including the relative absence of formal management
plans and limited efforts toward local community beneficiation, and how such
contextual differences may confound PAME scores when indicator weights are
treated equal.
PMID- 25850616
TI - Multi-layered polymeric nanoparticles for pH-responsive and sequenced release of
theranostic agents.
AB - In this study, multi-layered pH-responsive polymeric nanoparticles (NPs) are
prepared by multiple (up to 4) emulsifications to encapsulate multiple
hydrophilic and hydrophobic theranostic agents for controlled and sequenced
release. It is found that the sequence of release of multiple chemotherapeutic
agents from the NPs significantly affects their efficacy against cancer cells.
PMID- 25850617
TI - Constrained Dual Scaling for Detecting Response Styles in Categorical Data.
AB - Dual scaling (DS) is a multivariate exploratory method equivalent to
correspondence analysis when analysing contingency tables. However, for the
analysis of rating data, different proposals appear in the DS and correspondence
analysis literature. It is shown here that a peculiarity of the DS method can be
exploited to detect differences in response styles. Response styles occur when
respondents use rating scales differently for reasons not related to the
questions, often biasing results. A spline-based constrained version of DS is
devised which can detect the presence of four prominent types of response styles,
and is extended to allow for multiple response styles. An alternating nonnegative
least squares algorithm is devised for estimating the parameters. The new method
is appraised both by simulation studies and an empirical application.
PMID- 25850618
TI - An Exact Method for Partitioning Dichotomous Items Within the Framework of the
Monotone Homogeneity Model.
AB - The monotone homogeneity model (MHM-also known as the unidimensional monotone
latent variable model) is a nonparametric IRT formulation that provides the
underpinning for partitioning a collection of dichotomous items to form scales.
Ellis (Psychometrika 79:303-316, 2014, doi: 10.1007/s11336-013-9341-5 ) has
recently derived inequalities that are implied by the MHM, yet require only the
bivariate (inter-item) correlations. In this paper, we incorporate these
inequalities within a mathematical programming formulation for partitioning a set
of dichotomous scale items. The objective criterion of the partitioning model is
to produce clusters of maximum cardinality. The formulation is a binary integer
linear program that can be solved exactly using commercial mathematical
programming software. However, we have also developed a standalone branch-and
bound algorithm that produces globally optimal solutions. Simulation results and
a numerical example are provided to demonstrate the proposed method.
PMID- 25850620
TI - Neuroanatomical Diversity of Corpus Callosum and Brain Volume in Autism: Meta
analysis, Analysis of the Autism Brain Imaging Data Exchange Project, and
Simulation.
AB - BACKGROUND: Patients with autism have been often reported to have a smaller
corpus callosum (CC) than control subjects. METHODS: We conducted a meta-analysis
of the literature, analyzed the CC in 694 subjects of the Autism Brain Imaging
Data Exchange project, and performed computer simulations to study the effect of
different analysis strategies. RESULTS: Our meta-analysis suggested a group
difference in CC size; however, the studies were heavily underpowered (20% power
to detect Cohen's d = .3). In contrast, we did not observe significant
differences in the Autism Brain Imaging Data Exchange cohort, despite having
achieved 99% power. However, we observed that CC scaled nonlinearly with brain
volume (BV): large brains had a proportionally smaller CC. Our simulations showed
that because of this nonlinearity, CC normalization could not control for
eventual BV differences, but using BV as a covariate in a linear model would. We
also observed a weaker correlation of IQ and BV in cases compared with control
subjects. Our simulations showed that matching populations by IQ could then
induce artifactual BV differences. CONCLUSIONS: The lack of statistical power in
the previous literature prevents us from establishing the reality of the claims
of a smaller CC in autism, and our own analyses did not find any. However, the
nonlinear relationship between CC and BV and the different correlation between BV
and IQ in cases and control subjects may induce artifactual differences. Overall,
our results highlight the necessity for open data sharing to provide a more solid
ground for the discovery of neuroimaging biomarkers within the context of the
wide human neuroanatomical diversity.
PMID- 25850621
TI - Nesfatin-1 and the Cardiovascular System: Central and Pheripheral Actions and
Cardioprotection.
AB - Recently, the hypothalamic 82-aa peptide Nesfatin-1 received notable attention
for its anorexigenic and anti-hyperglycemic properties. In mammalian
hypothalamus, Nesfatin-1 is expressed, together with the precursor Nucleobindin 2
(NUCB2), in regions controlling water-food intake, body weight, and glucose
homeostasis. The peptide is also peripherally expressed, as shown in the rat
heart, in which it is present together with NUCB2. In addition to a central
modulation of nutrition and energy balance, and of the nervous circuits
responsible for blood pressure and heart rate control, Nesfatin-1 also acts
peripherally on several districts, including the cardiovascular (CV) system.
Accordingly, the peptide is regarded with interest as a multifunctional hormone
not only linked to alimentary homeostasis. This review aims to analyze the
literature on Nesfatin-1, with focus on its emerging CV activity. Few available
studies show that the peptide affects energy metabolism of murine and human
cardiomyocytes, by eliciting insulin-like effects. On the ex vivo rat heart, it
directly depresses contractility and relaxation via cGMP, PKG and ERK1/2, and
limits ischemia/reperfusion (I/R) damage, acting in post-conditioning protection.
Nesfatin-1 actions are proposed to involve an unknown G-protein coupled receptor.
However, in the rat heart, functional studies, co-immunoprecipitation and local
sequence alignment analyses suggest an interaction with the Natriuretic Peptide
Receptor-type A (NPR-A). These data open up novel perspectives to clarify not
only the biological significance of the peptide, but also its putative biomedical
potential in the presence of nutrition-dependent cardiovascular diseases.
PMID- 25850622
TI - Identification of Lipid Species Linked to the Progression of Non-Alcoholic Fatty
Liver Disease.
AB - Non-alcoholic fatty liver disease (NAFLD) is histologically characterized by the
aberrant accumulation of lipid droplets in the liver, which is positively
correlated with insulin resistance. Within the spectrum of this disease, patients
can develop hepatitis and cirrhosis; i.e., non-alcoholic steatohepatitis (NASH).
The mechanisms responsible for the progression of NAFLD are not fully understood.
Triacylglycerol (TAG), which is mainly found in lipid droplets, is currently
considered to act as a buffer against the accumulation of non-TAG toxic lipid
species. In line with this, recent studies have revealed that insulin resistance
is driven by the accumulation of phosphatidic acid and diacylglycerol in
hepatocytes and that cholesterol-overloaded stellate cells are associated with
fibrosis in the liver. Therefore, it is important to identify the toxic lipid
species that contribute to NAFLD progression in order to clarify the pathogenesis
of NASH and find novel targets for its treatment. In this review, we divided
lipids into five classes; i.e., into fatty acyls, glycerophospholipids,
glycerolipids, sphingolipids, and sterol lipids, and described their molecular
structures, distributions, and metabolism under physiological conditions, as well
as the contributions they make to the progression of NAFLD.
PMID- 25850619
TI - Brain rhythms connect impaired inhibition to altered cognition in schizophrenia.
AB - In recent years, schizophrenia research has focused on inhibitory interneuron
dysfunction at the level of neurobiology and on cognitive impairments at the
psychological level. Reviewing both experimental and computational findings, we
show how the temporal structure of the activity of neuronal populations,
exemplified by brain rhythms, can begin to bridge these levels of complexity.
Oscillations in neuronal activity tie the pathophysiology of schizophrenia to
alterations in local processing and large-scale coordination, and these
alterations in turn can lead to the cognitive and perceptual disturbances
observed in schizophrenia.
PMID- 25850623
TI - mTOR: A Novel Therapeutic Target for Diseases of Multiple Systems.
AB - Significant progress in the research of mammalian target of rapamycin (mTOR) in
recent years, has greatly enhanced our understanding of the role and cellular
pathways through which mTOR control cellular processes, such as translational
initiation, actin organization, cell proliferation, and cell survival. mTOR is
activated by phosphorylation and functions mainly through mTOR complex 1 or mTOR
complex 2. mTORC1 is activated through tuberous sclerosis complex 1/2 dependent
and independent mechanisms following the stimulation by growth factors, nutrient,
amino acids, and other signaling pathways. The activity of mTOR is closely
associated with cell proliferation and differentiation, apoptosis, and autophagy.
Activation of mTOR prevents the induction of both apoptosis and autophagy through
regulating its multiple targets. Given that the activity of mTOR has been
involved in the pathogenesis of neurodegenerative disorders, cardiovascular
abnormalities, metabolic diseases, renal transplantation, autoimmune
abnormalities, and cancer, manipulating mTOR activation may represent as an
innovative therapeutic strategy for these diseases. Yet, the role of mTOR in the
body is complicated and therefore, its activity needs to be tightly regulated to
achieve beneficial outcome in a specific pathological condition.
PMID- 25850624
TI - Role of Free Fatty Acid Receptor 2 (FFAR2) in the Regulation of Metabolic
Homeostasis.
AB - Besides being an important source of fuel and structural components of biological
membranes, free fatty acids (FFAs) are known to display a wide variety of roles
that include modulation of receptor signaling and regulation of gene expression
among many. FFAs play a significant role in maintaining metabolic homeostasis by
activating specific G-Protein Coupled Receptors (GPCRs) in pancreatic beta cells,
immune cells, white adipose tissue, intestine and several other tissues. Free
Fatty acid receptor 2 (FFAR2) also known as GPR43 belongs to this group of GPCRs
and has been shown to participate in a number of important biological activities.
FFAR2 is activated by short-chain fatty acids (SCFAs) such as acetate, propionate
and butyrate. SCFAs are formed in the distal gut by bacterial fermentation of
macro-fibrous material that escapes digestion in the upper gastrointestinal tract
and enters the colon and have been shown to play vital role in the immune
regulation and metabolic homeostasis. FFAR2 and other free fatty acid receptors
are considered key components of the body's nutrient sensing mechanism and
targeting these receptors is assumed to offer novel therapies for the management
of diabetes and other metabolic disorders. This review aims to summarize the
current state of our understanding of FFAR2 biology with a particular focus on
its role in metabolic homeostasis.
PMID- 25850625
TI - Bridging the Gap: The Potential Role of Corticosteroid Binding Globulin in
Cardiac Steroid Facilitation.
AB - Corticosteroid (glucocorticoids [GCs] and mineralcorticoids [MCs]) interact
directly with cells of the cardiovascular system. Their signaling affects genomic
and non-genomic receptors and comprises a multitude of alternative and
interfering levels of interaction, which influence the physiological response.
This review describes genomic and non-genomic pathways of steroid facilitation
and portrays the current body of knowledge regarding corticosteroid-binding
globulin (CBG). The latter is a carrier protein facilitating corticosteroid
availability in the circulation and has recently been discovered intrinsically in
cardiomyocytes. Thought experiments highlight potential areas of clinical
research and hypotheses are presented for steroid- carrier interaction.
Furthermore, this review comprises a conclusive overview of disease conditions
and substances that influence CBG levels and summarizes the potential of CBG as a
potential future biomarker.
PMID- 25850626
TI - Use of extramural ambulatory care curricula in postgraduate medical training.
AB - INTRODUCTION: Extramural curricula developed for the purpose of sharing with
other institutions have been designed to improve education on important topics in
ambulatory care. We sought to assess the usage rates of these curricula among
paediatric, internal medicine, and combined medicine-paediatrics residency
programmes in the United States. METHODS: Surveys on aspects of trainee
continuity clinic were sent to paediatric and medicine-paediatrics programme
directors in 2012. Surveys contained an item asking respondents about their use
of extramural ambulatory care curricula. Since no similar recent data were
available for internal medicine, and to verify the accuracy of the paediatric
survey data, we queried the editors of four widely used curricula for
subscription information. Descriptive and inferential statistics were calculated.
RESULTS: Responses from paediatric programmes indicated that 48 of 111 (43 %)
were using an extramural curriculum, compared with 39 of 60 (65 %) medicine
paediatrics programmes (p = 0.007). Editor query revealed a collective
subscription rate of internal medicine programmes (300 of 402, 75 %), which was
greater than the subscription rate of paediatric programmes (90 of 201, 45 %) (p
< 0.001). DISCUSSION: Training programmes in paediatrics, internal medicine, and
combined medicine-paediatrics utilize extramural curricula to guide education in
ambulatory care, but internal medicine and medicine-paediatrics programmes employ
these curricula at greater rates than paediatric programmes.
PMID- 25850627
TI - The writer's craft.
PMID- 25850629
TI - Treatment of recurrent anal fistula using an autologous cartilage plug: a pilot
study.
AB - BACKGROUND: The aim of the present study was to assess a novel autologous
cartilage plug technique used to treat anal fistula in ten patients. METHODS: All
ten patients had undergone at least two prior operations for recurrent fistulas.
The plugs were prepared using the patients' own cartilage, which was obtained
from either the nose or the ear, diced into pieces, and wrapped with oxidized
regenerated cellulose. During the same session, fistula tracts were curetted
using cytology brushes, and then, the cartilage plug was inserted into the tract.
Routine postoperative examinations were performed at 2, 4, 8, 12, and 24 weeks
after surgery. Magnetic resonance imaging was performed before surgery and at 3
and 6 months postoperatively. Relief of symptoms, radiological healing,
recurrence, and continence were evaluated. RESULTS: The ten patients included six
males and four females, with a median age of 39 years (range 25-70 years) and a
median of three previous fistula operations (range 2-7 operations). Nine patients
had cryptoglandular abscess, and one patient had Crohn's disease. The majority of
the patients had transsphincteric fistulas with substantial anal sphincter
involvement. The cartilage donor site was the nose for one patient and the ear
for nine patients. The median follow-up time was 24 months (range 10-32 months).
Of the ten patients, nine had fistula treatment without any short-term
complications. The fistula failed to heal in one patient. Among the nine patients
whose operations were initially successful, two late recurrences were observed.
CONCLUSIONS: The cartilage plug seems to be a promising alternative for anal
fistula treatment.
PMID- 25850628
TI - A US Multicenter Study of Safety and Efficacy of Fully Covered Self-Expandable
Metallic Stents in Benign Extrahepatic Biliary Strictures.
AB - BACKGROUND: Endoscopic therapy is considered first line for management of benign
biliary strictures (BBSs). Placement of plastic stents has been effective but
limited by their short-term patency and need for repeated procedures. Fully
covered self-expandable metallic stents (FCSEMSs) offer longer-lasting biliary
drainage without the need for frequent exchanges. AIMS: The aim of this study was
to assess the efficacy and safety of FCSEMS in patients with BBS. METHODS: A
retrospective review of all patients who underwent ERCP and FCSEMS placement at
five tertiary referral US hospitals was performed. Stricture resolution and
adverse events related to ERCP and/or stenting were recorded. RESULTS: A total of
123 patients underwent FCSEMS placement for BBS and 112 underwent a subsequent
follow-up ERCP. The mean age was 62 years (+/-15.6), and 57% were males.
Stricture resolution occurred in 81% of patients after a mean of 1.2 stenting
procedures (mean stent dwell time 24.4 +/- 2.3 weeks), with a mean follow-up of
18.5 months. Stricture recurrence occurred in 5 patients, and 3 patients required
surgery for treatment of refractory strictures. Stent migration (9.7%) was the
most common complication, followed by stent occlusion (4.9%), cholangitis (4.1%),
and pancreatitis (3.3%). There was one case of stent fracture during removal, and
one stent could not be removed. There was one death due to cholangitis.
CONCLUSIONS: Majority of BBS can be successfully managed with 1-2 consecutive
FCSEMS with stent dwell time of 6 months.
PMID- 25850630
TI - A rare perianal tumor: solitary fibrous tumor.
PMID- 25850632
TI - A Case Report of Acute Vitamin A Intoxication due to Ocean Perch Liver Ingestion.
AB - BACKGROUND: Chronic vitamin A intoxication is well known; however, there are few
reports of acute vitamin A intoxication due to the ingestion of food rich in
vitamin A, particularly in adults. CASE REPORT: We report a case of a 27-year-old
man presenting with chief complaints of flushing, headache, nausea, and joint
pain. He had consumed 800 g of grilled ocean perch liver the day before and had
experienced numbness shortly after. Although physical examination revealed only
facial flushing, we suspected acute vitamin A intoxication due to his diet
history. On day 2 after ingestion, his serum retinol levels were elevated at 1577
ng/mL, which confirmed vitamin A intoxication. He returned for follow-up on day 4
after ingestion, by which time his presenting symptoms had improved, but he had
developed desquamation of his facial skin. WHY SHOULD AN EMERGENCY PHYSICIAN BE
AWARE OF THIS?: Emergency physicians should consider acute vitamin A intoxication
in the differential diagnosis of patients with headache, flushing, desquamation,
nausea, and vomiting of unknown etiology. Complete diet histories and checking
vitamin A levels are essential for diagnosis. This report highlights the
diagnostic difficulties associated with vitamin A intoxication and the importance
of an accurate diet history.
PMID- 25850633
TI - Safety and efficacy of milk and molasses enemas in the emergency department.
AB - BACKGROUND: Increased scrutiny is occurring from regulatory agencies about the
use of nonsterile enema preparations in the emergency department (ED) for
constipation. This includes the "off-label" use of milk and molasses (M&M)
enemas, as there are no reported data in the medical literature to determine
safety and efficacy. OBJECTIVES: To evaluate the success and complication rates
of administering M&M enemas in the ED. METHODS: This was a structured
retrospective study at two EDs over 8 years. Primary success was defined as the
patient having a bowel movement. Secondary measures of success included improved
pain score by 2 or more points or lowering of a heart rate initially over 100
beats/min by 20 or more beats/min. Complications included: hemodynamic
compromise, increased pain, electrolyte disturbances, bacteremia, bowel
perforation, rectal pain or bleeding, cardiac dysrhythmias, anaphylaxis,
electrolyte disturbances, dizziness or syncope, or hospital admission for issues
surrounding enema. RESULTS: There were 2013 enemas given, of which 261 were M&M
enemas; 214 were given alone. Success rates defined only as bowel evacuation for
M&M enemas alone were 87.9% (188/214) and, when used after other treatment
failures, were 82.4% (28/34) successful. Five additional patients improved with
the secondary measures (90.2% success). There were 8/261 complications (3.1%), of
which four had an increased heart rate, two had decreased blood pressure, one had
an increased pain score, and one subsequently developed a fever. CONCLUSION: M&M
enemas have a low complication rate when used in the ED.
PMID- 25850634
TI - Seeing eye to eye: becoming the chaplain in the emergency department of a level I
trauma center.
PMID- 25850635
TI - The Influence of Tactile Perception on Classification of Bone Tissue at Dental
Implant Insertion.
AB - BACKGROUND: Various ways of using the Lekholm and Zarb (L&Z) classification have
added to the lack of scientific evidence of the effectiveness of this clinical
method in the evaluation of implant treatment. PURPOSE: The study aims to assess
subjective jawbone classifications in patients referred for implant treatment,
using L&Z classification with and without surgeon's hand perception at implant
insertion. The association between bone type classifications and quantitative
parameters of primary implant stability was also assessed. MATERIALS AND METHODS:
One hundred thirty-five implants were inserted using conventional loading
protocol. Three surgeons classified bone quality at implant sites using two
methods: one based on periapical and panoramic images (modified L&Z) and one
based on the same images associated with the surgeon's tactile perception during
drilling (original L&Z). Peak insertion torque and implant stability quotient
(ISQ) were recorded. RESULTS: The modified and original L&Z were strongly
correlated (rho = 0.79; p < .001); Wilcoxon signed-rank test showed no
significant difference in the distribution of bone type classification between
pairs using the two methods (p = .538). Spearman correlation tested the
association between primary stability parameters and bone type classifications (
0.34 to -0.57 [p < .001]). CONCLUSIONS: Tactile surgical perception has a minor
influence on rating of subjective bone type for dental implant treatment using
the L&Z classification.
PMID- 25850636
TI - Patients with Psychiatric Disorders Can Also Have CLABSIs: A Response to "CLABSI
or Munchausen's or Both".
PMID- 25850637
TI - Characteristics and Diagnostic Yield of Pediatric Colonoscopy in Taiwan.
AB - BACKGROUND: Colonoscopy of the lower gastrointestinal tract has diagnostic and
therapeutic value. This retrospective study aimed to investigate the indications,
complications, and diagnostic yield of diagnostic colonoscopy among Taiwanese
children. METHODS: The application of colonoscopy performed on children aged < 18
years between 1998 and 2010 in a referral tertiary center in Southern Taiwan was
reviewed. Data on age, gender, indications, complications, and colonoscopic and
final diagnoses were collected and analyzed. RESULTS: One hundred and ninety-two
children with 201 colonoscopies and 27 sigmoidoscopies were enrolled. The rate of
successful ileocecal approach was 77.5%. The most common indication was lower
gastrointestinal bleeding (LGIB; 53.5%), followed by chronic abdominal pain
(20.6%), iron deficiency anemia (IDA; 11.8%), and chronic diarrhea (11.4%). There
were 144 patients (75%) with a conclusive diagnosis in their first colonoscopy,
including nonspecific colitis (23.4%), polyp (20.4%), and inflammatory bowel
disease (8.3%). The diagnostic yields of colonoscopy according to the major
indications were 77.3% in LGIB, 68.1% in chronic abdominal pain, 66.7% in IDA,
and 79.2% in chronic diarrhea. Among the patients with LGIB, juvenile polyp
(26.4%) was the most common etiology. There were no major procedure-related
complications. CONCLUSION: LGIB is the most common indication for pediatric
colonoscopy. Pediatric colonoscopy is most effective in diagnosing pediatric LGIB
and chronic diarrhea.
PMID- 25850638
TI - CORAL: model for no observed adverse effect level (NOAEL).
AB - The in vivo repeated dose toxicity (RDT) test is intended to provide information
on the possible risk caused by repeated exposure to a substance over a limited
period of time. The measure of the RDT is the no observed adverse effect level
(NOAEL) that is the dose at which no effects are observed, i.e., this endpoint
indicates the safety level for a substance. The need to replace in vivo tests, as
required by some European Regulations (registration, evaluation authorization and
restriction of chemicals) is leading to the searching for reliable alternative
methods such as quantitative structure-activity relationships (QSAR). Considering
the complexity of the RDT endpoint, for which data quality is limited and depends
anyway on the study design, the development of QSAR for this endpoint is an
attractive task. Starting from a dataset of 140 organic compounds with NOAEL
values related to oral short term toxicity in rats, we developed a QSAR model
based on optimal descriptors calculated with simplified molecular input-line
entry systems and the graph of atomic orbitals by the Monte Carlo method, using
CORAL software. Three different splits into the training, calibration, and
validation sets are studied. The mechanistic interpretation of these models in
terms of molecular fragment with positive or negative contributions to the
endpoint is discussed. The probabilistic definition for the domain of
applicability is suggested.
PMID- 25850631
TI - Laparoscopic cholecystectomy: consensus conference-based guidelines.
AB - INTRODUCTION: Laparoscopic cholecystectomy (LC) is the gold standard technique
for gallbladder diseases in both acute and elective surgery. Nevertheless,
reports from national surveys still seem to represent some doubts regarding its
diffusion. There is neither a wide consensus on its indications nor on its
possible related morbidity. On the other hand, more than 25 years have passed
since the introduction of LC, and we have all witnessed the exponential growth of
knowledge, skill and technology that has followed it. In 1995, the EAES published
its consensus statement on laparoscopic cholecystectomy in which seven main
questions were answered, according to the available evidence. During the
following 20 years, there have been several additional guidelines on LC, mainly
focused on some particular aspect, such as emergency or concomitant biliary tract
surgery. METHODS: In 2012, several Italian surgical societies decided to revisit
the clinical recommendations for the role of laparoscopy in the treatment of
gallbladder diseases in adults, to update and supplement the existing guidelines
with recommendations that reflect what is known and what constitutes good
practice concerning LC.
PMID- 25850640
TI - Presurgical MR Imaging in Epilepsy.
AB - Primary goal of magnetic resonance imaging in epilepsy patients is to detect
epileptogenic lesions with small lesions best detectable on a 3D FLAIR SPACE
sequence with 1 mm(3) voxels. Morphometric analysis of 3D T1-weighted data sets
helps to find subtle lesions and may reveal the true extent of a lesion. In
further presurgical work-up, language lateralization and spatial relationship of
epileptogenic lesions to eloquent cortex and white matter tracts must be
evaluated. With clear left lateralization language, fMRI is sufficient; in
atypical lateralizations, Wada test and electrical stimulation mapping may be
added. Primary motor cortex and corticospinal tract on one and visual cortex and
optic radiation on the other side are displayed with fMRI and diffusion tensor
tractography. For the corticospinal tract a "global" tracking algorithm, for the
optic radiation including Meyer' loop, which may be damaged in anterior temporal
lobe resections, a probabilistic algorithm is best suited.
PMID- 25850641
TI - [With increasing weight there is also increasing risk].
PMID- 25850639
TI - In vivo stimulation of early peripheral axon regeneration by N
propionylmannosamine in the presence of polysialyltransferase ST8SIA2.
AB - The key enzyme of sialic acid (Sia) biosynthesis is the bifunctional UDP-N
acetylglucosamine 2-epimerase/ManNAc kinase (GNE/MNK). It metabolizes the
physiological precursor ManNAc and N-acyl modified analogues such as N
propionylmannosamine (ManNProp) to the respective modified sialic acid.
Polysialic acid (polySia) is a crucial compound for several functions in the
nervous system and is synthesized by the polysialyltransferases ST8SIA2 and
ST8SIA4. PolySia can be modified in vitro and in vivo by metabolic
glycoengineering of the N-acyl side chain of Sia. In vitro studies show that the
application of ManNProp increases neurite outgrowth and accelerates the re
establishment of functional synapses. In this study, we investigate in vivo how
ManNProp application might benefit peripheral nerve regeneration. In mice
expressing axonal fluorescent proteins (thy-1-YFP), we transected the sciatic
nerve and then replaced part of it with a sciatic nerve graft from non-expressing
mice (wild-type mice or St8sia2(-/-) mice). Analyses conducted 5 days after
grafting showed that systemic application of ManNProp (200 mg/kg, twice a day,
i.p.), but not of physiological ManNAc (1 g/kg, twice a day, i.p.), significantly
increased the extent of axonal elongation, the number of arborizing axons and the
number of branches per regenerating axon within the grafts from wild-type mice,
but not in those from St8sia2(-/-) mice. The results demonstrate that the
application of ManNProp has beneficial effects on early peripheral nerve
regeneration and indicate that the stimulation of axon growth depends on ST8SIA2
activity in the nerve graft.
PMID- 25850643
TI - [New short-acting local anaesthetics for spinal anaesthesia - Well-tried
substances for ambulatory surgery].
AB - More and more operative procedures are performed in an ambulatory setting. Many
patients are denied spinal anaesthesia, although it provides several advantages.
Innovative pharmaceutical formulations of well-tried local anaesthetics have
created "new" substances that are ideal for ambulatory surgery due to their fast
onset, short duration of action, and very low incidence of complications such as
transient neurological symptoms (TNS). Both hyperbaric prilocaine 2% and
preservative-free chloroprocaine 1% were recently approved for spinal application
in Germany. Additional perioperative measures, such as the use of atraumatic,
thin spinal needles (25 or 27G), restrictive volume management, and early patient
mobilisation, lead to a further reduction of complications. The new S1 guideline
of the German Society of Anaesthesiology and Intensive Care Medicine encourages
us anaesthetists to use spinal anaesthesia more frequently in an ambulatory
setting.
PMID- 25850644
TI - [Perioperative management of adult patients with obstructive sleep apnea].
AB - Obstructive sleep apnea (OSA) is a common sleep related breathing disorder with
an increasing prevalence. Most surgical patients with OSA have not been diagnosed
prior to surgery and are at an increased risk of developing perioperative
complications. Preoperative identification of these patients is important in
order to take appropriate measures concerning a safe perioperative management.
While the level of scientific evidence for single measures is still low, several
steps seem prudent: Preoperatively, sedating medications should only be applied
with extreme caution. Anesthetic management should focus on regional anesthetic
techniques and reduction of systemic opioids. In the case of general anesthesia,
an increased risk of a patient presenting with a difficult airway should be
appreciated. The extent and duration of postoperative continuous monitoring has
to be determined on an individual basis. A preoperatively existing therapy with
continuous positive airway pressure should be continued postoperatively as soon
as possible. Patients with OSA may be managed on an outpatient basis if certain
requirements are met.
PMID- 25850645
TI - [Invasive emergency techniques - In-field-amputation].
AB - On-scene invasive emergency procedures, such as Cricothyroidotomy, chest drain,
intraosseous puncture or even in-field-amputation, are often unavoidable, when
indicated, and present a major challenge for the emergency physician. Personal,
temporal or local conditions are often unsuitable. Even with regular intervention
by the Emergency Medical Service, "last resort" measures occur very infrequently,
particularly in relation to paediatric emergencies. As well as theoretical
training, practice-oriented course concepts are essential in order to achieve
high quality in these procedures. This article presents the use of in-field
amputation, with reference to indication, implementation, problems and risks. It
is part of a series of four articles on the subject of invasive emergency
techniques.
PMID- 25850646
TI - [Pssst ... AINS secrets! --now from bariatric surgery].
PMID- 25850647
TI - [Patient autonomy and education -- for patients].
PMID- 25850648
TI - [Patient autonomy and informed consent - ethical and legal issues].
AB - Informing patients about the benefits and risks of and alternatives to proposed
medical or surgical procedures is crucial to the patient-physician relationship.
It is a legal and ethical precondition to a patient's informed consent to a
course of action. Particularly in cases of serious illness and when there are far
reaching implications for a patient's lifestyle, this process entails much more
than just imparting information. Indeed, it is a dialogue through which the
physician empowers the patient to reach a decision which reflects the patient's
life situation and system of values. This process promotes patient autonomy.
Studies have shown that this approach builds trust, increases patient
satisfaction with health care and results in a higher degree of professional
fulfilment for the physician.
PMID- 25850649
TI - [Health care power of attorney project at the University Hospital Frankfurt].
AB - Under German law it is the patient alone who has the right to decide whether or
not to undergo a particular medical procedure. Treating a patient without his or
her consent always constitutes a serious infringement of the patient's
constitutional right of self-determination as well as the right to physical
integrity. By issuing a power of attorney in health care matters to a person he
or she trusts, a patient can safeguard his or her rights in the event of
incapacitation. At the University Hospital Frankfurt patients who are scheduled
for major elective surgery are informed about the advantages of a health care
power of attorney during premedication. The University Hospital has developed its
own health care power of attorney form for patient use. In addition, patients
have the option of receiving additional information about other types of health
care advance directives, such as a living will.
PMID- 25850652
TI - Potentiometric sensing array for monitoring aquatic systems.
AB - Since aquatic environments are highly heterogeneous and dynamic, there is the
need in aquatic ecosystem monitoring to replace traditional approaches based on
periodical sampling followed by laboratory analysis with new automated techniques
that allow one to obtain monitoring data with high spatial and temporal
resolution. We report here on a potentiometric sensing array based on polymeric
membrane materials for the continuous monitoring of nutrients and chemical
species relevant for the carbon cycle in freshwater ecosystems. The proposed
setup operates autonomously, with measurement, calibration, fluidic control and
acquisition triggers all integrated into a self-contained instrument.
Experimental validation was performed on an automated monitoring platform on lake
Greifensee (Switzerland) using potentiometric sensors selective for hydrogen
ions, carbonate, calcium, nitrate and ammonium. Results from the field tests were
compared with those obtained by traditional laboratory analysis. A linear
correlation between calcium and nitrate activities measured with ISEs and
relevant concentrations measured in the laboratory was found, with the slopes
corresponding to apparent single ion activity coefficients gamma(*)(Ca(2+)) =
0.55(SD = 0.1mM) and gamma(*)(NO(3)(-)) = 0.75(SD = 4.7MUm). Good correlation
between pH values measured with ISE and CTD probes (SD = 0.2 pH) suggests
adequate reliability of the methodology.
PMID- 25850653
TI - Alternative CD44 splicing identifies epithelial prostate cancer cells from the
mesenchymal counterparts.
AB - An epithelial to mesenchymal transition (EMT) has been shown to be a necessary
precursor to prostate cancer metastasis. Additionally, the differential
expression and splicing of mRNAs has been identified as a key means to
distinguish epithelial from mesenchymal cells by qPCR, western blotting and
immunohistochemistry. However, few markers exist to differentiate between these
cells by flow cytometry. We previously developed two cell lines, PC3-Epi
(epithelial) and PC3-EMT (mesenchymal). RNAseq was used to determine the
differential expression of membrane proteins on PC3-Epi/EMT. We used western
blotting, qPCR and flow cytometry to validate the RNAseq results. CD44 was one of
six membrane proteins found to be differentially spliced between epithelial and
mesenchymal PC3 cells. Although total CD44 was positive in all PC3-Epi/EMT cells,
PC3-Epi cells had a higher level of CD44v6 (CD44 variant exon 6). CD44v6 was able
to differentiate epithelial from mesenchymal prostate cancer cells using either
flow cytometry, western blotting or qPCR.
PMID- 25850654
TI - The prostaglandin D2 receptor CRTH2 regulates accumulation of group 2 innate
lymphoid cells in the inflamed lung.
AB - Group 2 innate lymphoid cells (ILC2s) promote type 2 cytokine-dependent immunity,
inflammation, and tissue repair. Although epithelial cell-derived cytokines
regulate ILC2 effector functions, the pathways that control the in vivo migration
of ILC2s into inflamed tissues remain poorly understood. Here, we provide the
first demonstration that expression of the prostaglandin D2 (PGD2) receptor CRTH2
(chemoattractant receptor-homologous molecule expressed on Th2 cells) regulates
the in vivo accumulation of ILC2s in the lung. Although a significant proportion
of ILC2s isolated from healthy human peripheral blood expressed CRTH2, a smaller
proportion of ILC2s isolated from nondiseased human lung expressed CRTH2,
suggesting that dynamic regulation of CRTH2 expression might be associated with
the migration of ILC2s into tissues. Consistent with this, murine ILC2s expressed
CRTH2, migrated toward PGD2 in vitro, and accumulated in the lung in response to
PGD2 in vivo. Furthermore, mice deficient in CRTH2 exhibited reduced ILC2
responses and inflammation in a murine model of helminth-induced pulmonary type 2
inflammation. Critically, adoptive transfer of CRTH2-sufficient ILC2s restored
pulmonary inflammation in CRTH2-deficient mice. Together, these data identify a
role for the PGD2-CRTH2 pathway in regulating the in vivo accumulation of ILC2s
and the development of type 2 inflammation in the lung.
PMID- 25850655
TI - Characterization of host immunity during persistent vaginal colonization by Group
B Streptococcus.
AB - Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive
bacterium, which colonizes the vaginal tract in 10-30% of women. Colonization is
transient in nature, and little is known about the host and bacterial factors
controlling GBS persistence. Gaining insight into these factors is essential for
developing therapeutics to limit maternal GBS carriage and prevent transmission
to the susceptible newborn. In this work, we have used human cervical and vaginal
epithelial cells, and our established mouse model of GBS vaginal colonization, to
characterize key host factors that respond during GBS colonization. We identify a
GBS strain that persists beyond a month in the murine vagina, whereas other
strains are more readily cleared. Correspondingly, we have detected differential
cytokine production in human cell lines after challenge with the persistent
strain vs. other GBS strains. We also demonstrate that the persistent strain more
readily invades cervical cells compared with vaginal cells, suggesting that GBS
may potentially use the cervix as a reservoir to establish long-term
colonization. Furthermore, we have identified interleukin-17 production in
response to long-term colonization, which is associated with eventual clearance
of GBS. We conclude that both GBS strain differences and concurrent host immune
responses are crucial in modulating vaginal colonization.
PMID- 25850657
TI - Addressing the experimental variability associated with the microbiota.
PMID- 25850656
TI - Epithelial-specific A2B adenosine receptor signaling protects the colonic
epithelial barrier during acute colitis.
AB - Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal
barrier function. Emerging evidence implicates extracellular adenosine signaling
in attenuating mucosal inflammation. We hypothesized that adenosine-mediated
protection from intestinal barrier dysfunction involves tissue-specific signaling
through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface.
To address this hypothesis, we combined pharmacologic studies and studies in mice
with global or tissue-specific deletion of the Adora2b receptor. Adora2b(-/-)
mice experienced a significantly heightened severity of colitis, associated with
a more acute onset of disease and loss of intestinal epithelial barrier function.
Comparison of mice with Adora2b deletion on vascular endothelial cells
(Adora2b(fl/fl)VeCadCre(+)) or intestinal epithelia (Adora2b(fl/fl)VillinCre(+))
revealed a selective role for epithelial Adora2b signaling in attenuating colonic
inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial
cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of
vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair
response. Similarly, in vivo studies in genetic mouse models or treatment studies
with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken
together, our results suggest that intestinal epithelial Adora2b signaling
provides protection during intestinal inflammation via enhancing mucosal barrier
responses.
PMID- 25850658
TI - Molecular characteristics of bap-positive Staphylococcus aureus strains from
dairy cow mastitis.
AB - The biofilm-associated protein (Bap) of Staphylococcus aureus is a high molecular
weight cell-wall-anchored protein involved in biofilm formation, first described
in bovine mastitis strains from Spain. So far, studies regarding Bap were mainly
based on the Spanish strain V329 and its mutants, but no information on the
genetic variability of bap-positive Staph. aureus strains is yet available in the
literature. The present study investigated the molecular characteristics of 8 bap
positive Staph. aureus strains from subclinical bovine mastitis, isolated in 5
herds; somatic cell counts (SCC) of milk samples were also registered. Strains
were characterised using MLST, SPA typing and microarray and the results were
compared with V329. All isolates from this study and V329 were assigned to ST126,
t605, but some molecular differences were observed. Only herd A and B strains
harboured the genes for beta-lactams resistance; the leukocidin D/E gene, a type
I site-specific deoxyribonuclease subunit, 3rd locus gene and serin-protease A
and B were carried by all strains, but not by V329, while serin-protease E was
absent in V329 and in another isolate. Four isolates and V329 harboured the
fibronectin-binding protein B gene. SCC showed the highest value in the milk
sample affected by the only strain carrying all the virulence factors considered.
Potential large variability of virulence was evidenced among V329 and all bap
positive Staph. aureus strains considered: the carriage of fnb could enhance the
accumulation of biofilm, but the lack of lukD/E and splA, B or E might decrease
the invasiveness of strain.
PMID- 25850660
TI - Diabetes: Therapy for gestational diabetes mellitus--time for a change?
PMID- 25850659
TI - Local and systemic effects of the multifaceted epicardial adipose tissue depot.
AB - Epicardial adipose tissue is a unique and multifaceted fat depot with local and
systemic effects. This tissue is distinguished from other visceral fat depots by
a number of anatomical and metabolic features, such as increased fatty acid
metabolism and a unique transcriptome enriched in genes that are associated with
inflammation and endothelial function. Epicardial fat and the heart share an
unobstructed microcirculation, which suggests these tissues might interact. Under
normal physiological conditions, epicardial fat has metabolic, thermogenic
(similar to brown fat) and mechanical (cardioprotective) characteristics.
Development of pathological conditions might drive the phenotype of epicardial
fat such that it becomes harmful to the myocardium and the coronary arteries. The
equilibrium between protective and detrimental effects of this tissue is fragile.
Expression of the epicardial-fat-specific transcriptome is downregulated in the
presence of severe and advanced coronary artery disease. Improved local
vascularization, weight loss and targeted medications can restore the protective
physiological functions of epicardial fat. Measurements of epicardial fat have
several important applications in the clinical setting: accurate measurement of
its thickness or volume is correlated with visceral adiposity, coronary artery
disease, the metabolic syndrome, fatty liver disease and cardiac changes. On
account of this simple clinical assessment, epicardial fat is a reliable marker
of cardiovascular risk and an appealing surrogate for assessing the efficacy of
drugs that modulate adipose tissues.
PMID- 25850662
TI - Obesity: Inhibiting PI3K reduces body weight in obese mice.
PMID- 25850663
TI - Microfluidic droplet-based liquid-liquid extraction: online model validation.
AB - Droplet-based liquid-liquid extraction in a microchannel was studied, both
theoretically and experimentally. A full 3D mathematical model, incorporating
convection and diffusion in all spatial directions along with the velocity
profile, was developed to depict the governing transport characteristics of
droplet-based microfluidics. The finite elements method, as the most common
macroscale simulation technique, was used to solve the set of differential
equations regarding conservation of moment, mass and solute concentration in a
two-domain system coupled by interfacial surface of droplet-based flow pattern.
The model was numerically verified and validated online by following the
concentrations of a solute in two phases within the microchannel. The relative
azobenzene concentration profiles in a methanol/n-octane two-phase system at
different positions along the channel length were retrieved by means of a thermal
lens microscopic (TLM) technique coupled to a microfluidic system, which gave
results of high spatial and temporal resolution. Very good agreement between
model calculations and online experimental data was achieved without applying any
fitting procedure to the model parameters.
PMID- 25850661
TI - Islet alpha cells and glucagon--critical regulators of energy homeostasis.
AB - Glucagon is secreted from islet alpha cells and controls blood levels of glucose
in the fasting state. Impaired glucagon secretion predisposes some patients with
type 1 diabetes mellitus (T1DM) to hypoglycaemia; whereas hyperglycaemia in
patients with T1DM or type 2 diabetes mellitus (T2DM) is often associated with
hyperglucagonaemia. Hence, therapeutic strategies to safely achieve euglycaemia
in patients with diabetes mellitus now encompass bihormonal approaches to
simultaneously deliver insulin and glucagon (in patients with T1DM) or reduce
excess glucagon action (in patients with T1DM or T2DM). Glucagon also reduces
food intake and increases energy expenditure through central and peripheral
mechanisms, which suggests that activation of signalling through the glucagon
receptor might be useful for controlling body weight. Here, we review new data
that is relevant to understanding alpha-cell biology and glucagon action in the
brain, liver, adipose tissue and heart, with attention to normal physiology, as
well as conditions associated with dysregulated glucagon action. The feasibility
and safety of current and emerging glucagon-based therapies that encompass both
gain-of-function and loss-of-function approaches for the treatment of T1DM, T2DM
and obesity is discussed in addition to developments, challenges and critical
gaps in our knowledge that require additional investigation.
PMID- 25850665
TI - Advanced endoscopic therapeutics in Barrett's neoplasia: where are we now and
where are we heading?
AB - Over the last 10 years, there have been considerable changes in how we manage
Barrett's neoplasia, with the shift away from conventional surgery and moving
toward endotherapy for treating dysplasia and early cancer. In this editorial, we
will review these changes and look forward to the possible developments which may
occur over the next decade.
PMID- 25850664
TI - Fluoxetine induces input-specific hippocampal dendritic spine remodeling along
the septotemporal axis in adulthood and middle age.
AB - Fluoxetine, a selective serotonin-reuptake inhibitor (SSRI), is known to induce
structural rearrangements and changes in synaptic transmission in hippocampal
circuitry. In the adult hippocampus, structural changes include neurogenesis,
dendritic, and axonal plasticity of pyramidal and dentate granule neurons, and
dedifferentiation of dentate granule neurons. However, much less is known about
how chronic fluoxetine affects these processes along the septotemporal axis and
during the aging process. Importantly, studies documenting the effects of
fluoxetine on density and distribution of spines along different dendritic
segments of dentate granule neurons and CA1 pyramidal neurons along the
septotemporal axis of hippocampus in adulthood and during aging are conspicuously
absent. Here, we use a transgenic mouse line in which mature dentate granule
neurons and CA1 pyramidal neurons are genetically labeled with green fluorescent
protein (GFP) to investigate the effects of chronic fluoxetine treatment (18
mg/kg/day) on input-specific spine remodeling and mossy fiber structural
plasticity in the dorsal and ventral hippocampus in adulthood and middle age. In
addition, we examine levels of adult hippocampal neurogenesis, maturation state
of dentate granule neurons, neuronal activity, and glutamic acid decarboxylase-67
expression in response to chronic fluoxetine in adulthood and middle age. Our
studies reveal that while chronic fluoxetine fails to augment adult hippocampal
neurogenesis in middle age, the middle-aged hippocampus retains high sensitivity
to changes in the dentate gyrus (DG) such as dematuration, hypoactivation, and
increased glutamic acid decarboxylase 67 (GAD67) expression. Interestingly, the
middle-aged hippocampus shows greater sensitivity to fluoxetine-induced input
specific synaptic remodeling than the hippocampus in adulthood with the stratum
oriens of CA1 exhibiting heightened structural plasticity. The input-specific
changes and circuit-level modifications in middle-age were associated with modest
enhancement in contextual fear memory precision, anxiety-like behavior and
antidepressant-like behavioral responses.
PMID- 25850666
TI - Arrhythmias, syncopy, and sudden death.
PMID- 25850667
TI - The first European Congress on e-Cardiology & e-Health.
PMID- 25850668
TI - Occurrences and behaviors of naphthenic acids in a petroleum refinery wastewater
treatment plant.
AB - Naphthenic acids (NAs) are one class of compounds in wastewaters from petroleum
industries that are known to cause toxic effects, and their removal from oilfield
wastewater is an important challenge for remediation of large volumes of
petrochemical effluents. The present study investigated occurrences and behaviors
of total NAs and aromatic NAs in a refinery wastewater treatment plant, located
in north China, which combined physicochemical and biological processes.
Concentrations of total NAs were semiquantified to be 113-392 MUg/L in wastewater
from all the treatment units, and the percentages of aromatic NAs in total NAs
was estimated to be 2.1-8.8%. The mass reduction for total NAs and aromatic NAs
was 15+/-16% and 7.5+/-24% after the physicochemical treatment, respectively.
Great mass reduction (total NAs: 65+/-11%, aromatic NAs: 86+/-5%) was observed in
the biological treatment units, and antiestrogenic activities observed in
wastewater from physicochemical treatment units disappeared in the effluent of
the activated sludge system. The distributions of mass fractions of NAs
demonstrated that biodegradation via activated sludge was the major mechanism for
removing alicyclic NAs, aromatic NAs, and related toxicities in the plant, and
the polycyclic NA congener classes were relatively recalcitrant to
biodegradation, which is a complete contrast to the preferential adsorption of
NAs with higher cyclicity (low Z value). Removal efficiencies of total NAs were
73+/-17% in summer, which were higher than those in winter (53+/-15%), and the
seasonal variation was possibly due to the relatively high microbial
biotransformation activities in the activated sludge system in summer (indexed by
O3-NAs/NAs). The results of the investigations indicated that biotransformation
of NA mixtures by the activated sludge system were largely affected by
temperature, and employing an efficient adsorbent together with biodegradation
processes would help cost-effectively remove NAs in petroleum effluents.
PMID- 25850669
TI - Evolution in action: giant ankyrins awake.
AB - Reporting in Developmental Cell, Stephan et al. (2015) demonstrate critical
axonal and presynaptic functions from acquisition of an enormous exon by the
Drosophila ank2 gene. They propose that highly elongated ank2-XL molecules,
associated with the plasma membrane through spectrin and ank2-L, extend deep into
the axoplasm to promote microtubule organization.
PMID- 25850670
TI - A noisy tug of war: the battle between transcript production and degradation in
the liver.
AB - Genetically identical cells in culture often exhibit significant variations, or
noise, in gene expression, largely due to transcriptional bursting. Halpern et
al. (2015) have developed methods to study gene bursting in tissues to find that
this transcriptional bursting also occurs in the mammalian liver and may
contribute to functional plasticity in hepatocytes.
PMID- 25850671
TI - Systemic organ wasting induced by localized expression of the secreted
insulin/IGF antagonist ImpL2.
AB - Organ wasting, related to changes in nutrition and metabolic activity of cells
and tissues, is observed under conditions of starvation and in the context of
diseases, including cancers. We have developed a model for organ wasting in adult
Drosophila, whereby overproliferation induced by activation of Yorkie, the Yap1
oncogene ortholog, in intestinal stem cells leads to wasting of the ovary, fat
body, and muscle. These organ-wasting phenotypes are associated with a reduction
in systemic insulin/IGF signaling due to increased expression of the secreted
insulin/IGF antagonist ImpL2 from the overproliferating gut. Strikingly,
expression of rate-limiting glycolytic enzymes and central components of the
insulin/IGF pathway is upregulated with activation of Yorkie in the gut, which
may provide a mechanism for this overproliferating tissue to evade the effect of
ImpL2. Altogether, our study provides insights into the mechanisms underlying
organ-wasting phenotypes in Drosophila and how overproliferating tissues adapt to
global changes in metabolism.
PMID- 25850672
TI - Malignant Drosophila tumors interrupt insulin signaling to induce cachexia-like
wasting.
AB - Tumors kill patients not only through well-characterized perturbations to their
local environment but also through poorly understood pathophysiological
interactions with distant tissues. Here, we use a Drosophila tumor model to
investigate the elusive mechanisms underlying such long-range interactions.
Transplantation of tumors into adults induces robust wasting of adipose, muscle,
and gonadal tissues that are distant from the tumor, phenotypes that resemble the
cancer cachexia seen in human patients. Notably, malignant, but not benign,
tumors induce peripheral wasting. We identify the insulin growth factor binding
protein (IGFBP) homolog ImpL2, an antagonist of insulin signaling, as a secreted
factor mediating wasting. ImpL2 is sufficient to drive tissue loss, and insulin
activity is reduced in peripheral tissues of tumor-bearing hosts. Importantly,
knocking down ImpL2, specifically in the tumor, ameliorates wasting phenotypes.
We propose that the tumor-secreted IGFBP creates insulin resistance in distant
tissues, thus driving a systemic wasting response.
PMID- 25850674
TI - Balancing acts of two HEAT subunits of condensin I support dynamic assembly of
chromosome axes.
AB - Condensin I is a five-subunit protein complex that plays a central role in
mitotic chromosome assembly and segregation in eukaryotes. To dissect its
mechanism of action, we reconstituted wild-type and mutant complexes from
recombinant subunits and tested their abilities to assemble chromosomes in
Xenopus egg cell-free extracts depleted of endogenous condensins. We find that
ATP binding and hydrolysis by SMC subunits have distinct contributions to the
action of condensin I and that continuous ATP hydrolysis is required for
structural maintenance of chromosomes. Mutant complexes lacking either one of two
HEAT subunits produce abnormal chromosomes with highly characteristic defects and
have contrasting structural effects on chromosome axes preassembled with the wild
type complex. We propose that balancing acts of the two HEAT subunits support
dynamic assembly of chromosome axes under the control of the SMC ATPase cycle,
thereby governing construction of rod-shaped chromosomes in eukaryotic cells.
PMID- 25850673
TI - A conserved phosphorylation switch controls the interaction between cadherin and
beta-catenin in vitro and in vivo.
AB - In metazoan adherens junctions, beta-catenin links the cytoplasmic tail of
classical cadherins to the F-actin-binding protein alpha-catenin. Phosphorylation
of a Ser/Thr-rich region in the cadherin tail dramatically enhances affinity for
beta-catenin and promotes cell-cell adhesion in cell culture systems, but its
importance has not been demonstrated in vivo. Here, we identify a critical
phosphorylated serine in the C. elegans cadherin HMR-1 required for strong
binding to the beta-catenin homolog HMP-2. Ablation of this phosphoserine
interaction produces developmental defects that resemble full loss-of-function
(Hammerhead and Humpback) phenotypes. Most metazoans possess a single gene for
beta-catenin, which is also a transcriptional coactivator in Wnt signaling.
Nematodes and planaria, however, have a set of paralogous beta-catenins; for
example, C. elegans HMP-2 functions only in cell-cell adhesion, whereas SYS-1
mediates transcriptional activation through interactions with POP-1/Tcf. Our
structural data define critical sequence differences responsible for the unique
ligand specificities of these two proteins.
PMID- 25850676
TI - Assessment of heterogeneity in types of vegetables served by main household food
preparers and food decision influencers.
AB - OBJECTIVE: While vegetables are often studied as one food group, global measures
may mask variation in the types and forms of vegetables preferred by different
individuals. To explore preferences for and perceptions of vegetables, we
assessed main food preparers based on their preparation of eight specific
vegetables and mushrooms. DESIGN: An online self-report survey. SETTING: Ontario,
Canada. Measures included perceived benefits and obstacles of vegetables,
convenience orientation and variety seeking in meal preparation. SUBJECTS: Of the
4517 randomly selected consumers who received the invitation, 1013 responded to
the survey (22.4 % response). Data from the main food preparers were analysed (n
756). RESULTS: Latent profile analysis indicated three segments of food
preparers. More open to new recipes, the 'crucifer lover' segment (13 %) prepared
and consumed substantially more Brussels sprouts, broccoli and asparagus than the
other segments. Although similar to the 'average consumer' segment (54 %) in many
ways, the 'frozen vegetable user' segment (33 %) used significantly more frozen
vegetables than the other segments due to higher prioritization of time and
convenience in meal preparation and stronger 'healthy=not tasty' perception.
Perception of specific vegetables on taste, healthiness, ease of preparation and
cost varied significantly across the three consumer segments. Crucifer lovers
also differed with respect to shopping and cooking habits compared with the
frozen vegetable users. CONCLUSIONS: The substantial heterogeneity in the types
of vegetables consumed and perceptions across the three consumer segments has
implications for the development of new approaches to promoting these foods.
PMID- 25850675
TI - Transcriptome dynamics of the stomatal lineage: birth, amplification, and
termination of a self-renewing population.
AB - Developmental transitions can be described in terms of morphology and the roles
of individual genes, but also in terms of global transcriptional and epigenetic
changes. Temporal dissections of transcriptome changes, however, are rare for
intact, developing tissues. We used RNA sequencing and microarray platforms to
quantify gene expression from labeled cells isolated by fluorescence-activated
cell sorting to generate cell-type-specific transcriptomes during development of
an adult stem-cell lineage in the Arabidopsis leaf. We show that regulatory
modules in this early lineage link cell types that had previously been considered
to be under separate control and provide evidence for recruitment of individual
members of gene families for different developmental decisions. Because stomata
are physiologically important and because stomatal lineage cells exhibit
exemplary division, cell fate, and cell signaling behaviors, this dataset serves
as a valuable resource for further investigations of fundamental developmental
processes.
PMID- 25850677
TI - Assessing potato tuber diel growth by means of X-ray computed tomography.
AB - The formation and development of belowground organs is difficult to study. X-ray
computed tomography (CT) provides the possibility to analyse and interpret subtle
volumetric changes of belowground organs such as tubers, storage roots and
nodules. Here, we report on the establishment of a method based on a voxel
dimension of 240 MUm and precision (standard deviation) of 30 MUL that allows
interpreting growth differences among potato tubers happening within 3 h. Plants
were not stressed by the application of X-ray radiation, which was shown both by
morphological comparison with control plants and by analysis of lipid
peroxidation as a measure of oxidative stress. Diel (24 h) tuber growth
fluctuations of three potato genotypes were monitored in soil-filled pots of 10
L. In contrast to the results from previous reports, most tubers grew at similar
rates during day and night. Tuber growth was not related to the developmental
stage of plants and tubers. Pronounced differences were observed between average
growth rates in different tubers within a plant. These results are discussed in
the context of restrictions of past methods to study tuber growth and in the
context of their potential for the characterization of the formation and
development of other belowground plant organs.
PMID- 25850678
TI - immunoClust--An automated analysis pipeline for the identification of
immunophenotypic signatures in high-dimensional cytometric datasets.
AB - Multiparametric fluorescence and mass cytometry offers new perspectives to
disclose and to monitor the high diversity of cell populations in the peripheral
blood for biomarker research. While high-end cytometric devices are currently
available to detect theoretically up to 120 individual parameters at the single
cell level, software tools are needed to analyze these complex datasets
automatically in acceptable time and without operator bias or knowledge. We
developed an automated analysis pipeline, immunoClust, for uncompensated
fluorescence and mass cytometry data, which consists of two parts. First, cell
events of each sample are grouped into individual clusters. Subsequently, a
classification algorithm assorts these cell event clusters into populations
comparable between different samples. The clustering of cell events is designed
for datasets with large event counts in high dimensions as a global unsupervised
method, sensitive to identify rare cell types even when next to large
populations. Both parts use model-based clustering with an iterative expectation
maximization algorithm and the integrated classification likelihood to obtain the
clusters. A detailed description of both algorithms is presented. Testing and
validation was performed using 1) blood cell samples of defined composition that
were depleted of particular cell subsets by magnetic cell sorting, 2) datasets of
the FlowCAP III challenges to identify populations of rare cell types and 3) high
dimensional fluorescence and mass-cytometry datasets for comparison with
conventional manual gating procedures. In conclusion, the immunoClust-algorithm
is a promising tool to standardize and automate the analysis of high-dimensional
cytometric datasets. As a prerequisite for interpretation of such data, it will
support our efforts in developing immunological biomarkers for chronic
inflammatory disorders and therapy recommendations in personalized medicine.
immunoClust is implemented as an R-package and is provided as source code from
www.bioconductor.org.
PMID- 25850679
TI - Physical characterization of wax/oil crystalline networks.
AB - The objective of this research was to evaluate the physical properties of
different types of wax/oil systems. Olive (OO), corn (CO), soybean (SBO),
sunflower (SFO), safflower (SAFO), and canola (CAO) oils were mixed with
sunflower oil wax (SFOW), paraffin wax (PW), and beeswax (BW) at different
concentrations (1% to 10%). Results from this study show that the physical
properties of wax/oil systems is affected not only by the concentration and type
of wax used, but also by the type of oil used. In general, wax/oil systems
formulated with SFOW generated crystalline networks with high enthalpies (1 to 22
J/g) and high G' values (2 to 6 * 10(6) Pa) compared with the values obtained for
BW and PW. SFOW crystalline networks were characterized by needle-like crystals
independently of the wax concentrations and type of oil used. BW crystalline
networks, however, were characterized by different crystal morphologies (needle
like or spherulites) depending on the wax concentration and type of oil used. PW
samples were characterized by a crystalline network formed by needle- and
platelet-like crystals. Enthalpy values of BW and PW samples were similar (0.3 to
20 J/g), but BW samples resulted in significantly higher (P < 0.05) G' values in
the 5% and 10% samples with values of 3.9 * 10(6) and 6.1 * 10(5) Pa for 10% BW
and PW, respectively.
PMID- 25850680
TI - Electronic Spectroscopy of [FePAH](+) Complexes in the Region of the Diffuse
Interstellar Bands: Multireference Wave Function Studies on [FeC6H6](+).
AB - The low-energy states and electronic spectrum in the near-infrared-visible region
of [FeC6H6](+) are studied by theoretical approaches. An exhaustive exploration
of the potential energy surface of [FeC6H6](+) is performed using the density
functional theory method. The ground state is found to be a (4)A1 state. The
structures of the lowest energy states ((4)A2 and (4)A1) are used to perform
multireference wave function calculations by means of the multistate complete
active space with perturbation at the second order method. Contrary to the
density functional theory results ((4)A1 ground state), multireference
perturbative calculations show that the (4)A2 state is the ground state. The
vertical electronic spectrum is computed and compared with the astronomical
diffuse interstellar bands, a set of near-infrared-visible bands detected on the
extinction curve in our and other galaxies. Many transitions are found in this
domain, corresponding to d -> d, d -> 4s, or d -> pi* excitations, but few are
allowed and, if they are, their oscillation strengths are small. Even though some
band positions could match some of the observed bands, the relative intensities
do not fit, making the contribution of the [Fe-C6H6](+) complexes to the diffuse
interstellar bands questionable. This work, however, lays the foundation for the
studies of polycyclic aromatic hydrocarbons (PAHs) complexed to Fe cations that
are more likely to possess d -> pi* and pi -> pi* transitions in the diffuse
interstellar bands domain. PAH ligands indeed possess a larger number of pi and
pi* orbitals, respectively, higher and lower in energy than those of C6H6, which
are expected to lead to lower energy d -> pi* and pi -> pi* transitions in
[FePAH](+) than in [FeC6H6](+) complexes.
PMID- 25850681
TI - Dereplication: racing to speed up the natural products discovery process.
AB - Covering: 1993-2014 (July)To alleviate the dereplication holdup, which is a major
bottleneck in natural products discovery, scientists have been conducting their
research efforts to add tools to their "bag of tricks" aiming to achieve faster,
more accurate and efficient ways to accelerate the pace of the drug discovery
process. Consequently dereplication has become a hot topic presenting a huge
publication boom since 2012, blending multidisciplinary fields in new ways that
provide important conceptual and/or methodological advances, opening up
pioneering research prospects in this field.
PMID- 25850682
TI - Dramatic erythroid response to low-dose thalidomide in two patients with
transfusion independent thalassemia and severe post-transfusional alloimmune
hemolysis.
PMID- 25850683
TI - Prediction of fruit and vegetable intake from biomarkers using individual
participant data of diet-controlled intervention studies.
AB - Fruit and vegetable consumption produces changes in several biomarkers in blood.
The present study aimed to examine the dose-response curve between fruit and
vegetable consumption and carotenoid (alpha-carotene, beta-carotene, beta
cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C
concentrations. Furthermore, a prediction model of fruit and vegetable intake
based on these biomarkers and subject characteristics (i.e. age, sex, BMI and
smoking status) was established. Data from twelve diet-controlled intervention
studies were obtained to develop a prediction model for fruit and vegetable
intake (including and excluding fruit and vegetable juices). The study population
in the present individual participant data meta-analysis consisted of 526 men and
women. Carotenoid, folate and vitamin C concentrations showed a positive
relationship with fruit and vegetable intake. Measures of performance for the
prediction model were calculated using cross-validation. For the prediction model
of fruit, vegetable and juice intake, the root mean squared error (RMSE) was
258.0 g, the correlation between observed and predicted intake was 0.78 and the
mean difference between observed and predicted intake was - 1.7 g (limits of
agreement: - 466.3, 462.8 g). For the prediction of fruit and vegetable intake
(excluding juices), the RMSE was 201.1 g, the correlation was 0.65 and the mean
bias was 2.4 g (limits of agreement: -368.2, 373.0 g). The prediction models
which include the biomarkers and subject characteristics may be used to estimate
average intake at the group level and to investigate the ranking of individuals
with regard to their intake of fruit and vegetables when validating
questionnaires that measure intake.
PMID- 25850684
TI - Gold Nanoparticle-Based Facile Detection of Human Serum Albumin and Its
Application as an INHIBIT Logic Gate.
AB - In this work, a facile colorimetric method is developed for quantitative
detection of human serum albumin (HSA) based on the antiaggregation effect of
gold nanoparticles (Au NPs) in the presence of HSA. The citrate-capped Au NPs
undergo a color change from red to blue when melamine is added as a cross-linker
to induce the aggregation of the NPs. Such an aggregation is efficiently
suppressed upon the adsorption of HSA on the particle surface. This method
provides the advantages of simplicity and cost-efficiency for quantitative
detection of HSA with a detection limit of ~1.4 nM by monitoring the colorimetric
changes of the Au NPs with UV-vis spectroscopy. In addition, this approach shows
good selectivity for HSA over various amino acids, peptides, and proteins and is
qualified for detection of HSA in a biological sample. Such an antiaggregation
effect can be further extended to fabricate an INHIBIT logic gate by using HSA
and melamine as inputs and the color changes of Au NPs as outputs, which may have
application potentials in point-of-care medical diagnosis.
PMID- 25850685
TI - Effect of oxygen and glucose deprivation on VEGF and its receptors in
microvascular endothelial cells co-cultured with mast cells.
AB - The aim of this study was to determine the correlation between angiogenesis and
the differential expression of vascular endothelial growth factor (VEGF) and its
receptors in myocardial microvascular endothelial cells (MMVECs) co-cultured with
mast cells (MCs) or mast cell granules (MCGs) under oxygen and glucose
deprivation (OGD). MMVECs and MCs were isolated from Wistar rats. MCs
spontaneously degranulated in OGD. The expression of VEGF peaked at 8 h and
decreased from 16 h in OGD. However, the expression of its receptor, fms-like
tyrosine kinase-1 (Flt-1), and fetal liver kinase-1 (Flk-1), decreased
significantly, and angiogenic potential of MMVECs decreased in OGD. Expression of
VEGF, Flt-1, and Flk-1 increased significantly when MMVECs were co-cultured with
MCGs or active MCs, but MCs had only a limited ability to induce angiogenesis in
OGD. The angiogenic potential of MMVECs cultured in OGD (even with MCGs) was
inferior to that of MMVECs cultured under normoxic conditions. OGD have a
profound effect on angiogenesis, which is more pronounced than the effect of MCs
on angiogenesis.
PMID- 25850686
TI - Intensive Care Infection Score--A new approach to distinguish between infectious
and noninfectious processes in intensive care and medicosurgical patients.
AB - OBJECTIVES: Clinicians regularly encounter substantial time delays in diagnosing
sepsis and administering appropriate antibiotic treatment. This study
investigated the ability of the Intensive Care Infection Score (ICIS) to
distinguish between infectious and noninfectious processes, and to assess the
justified commencement of antibiotic therapy retrospectively, in line with
hospital actual best practice and applied laboratory parameters. METHODS:
Intensive-care unit (ICU) patients were enrolled in this retrospective,
observational study. Clinical data and laboratory parameters were determined
daily. The cohort was divided into infected and noninfected patient groups.
RESULTS: Out of 172 ICU patients, including 72 postoperative patients, the
predictive value for infection throughout the first 5 days in 'all patients' and
the 'postoperative patient' group was highest for ICIS. An ICIS cut-off value of
three could predict infection in postoperative patients with 82.9% sensitivity
and 75.1% specificity. ICIS showed the lowest rate of potentially 'falsely
encouraged' and 'discouraged' antibiotic therapies for noninfected and for septic
postoperative patients, respectively, compared with C-reactive protein,
procalcitonin and white blood cell levels. CONCLUSIONS: In the ICU, particularly
for postoperative patients, ICIS is a reliable marker for the timely
identification of infection. ICIS may qualify as a new decision support tool for
antibiotic therapy, when interpreted within the clinical context.
PMID- 25850687
TI - Capabilities of a mobile extracorporeal membrane oxygenation service for severe
respiratory failure delivered by intensive care specialists.
AB - We conducted a single-centre observational study of retrievals for severe
respiratory failure over 12 months. Our intensivist-delivered retrieval service
has mobile extracorporeal membrane oxygenation capabilities. Sixty patients were
analysed: 34 (57%) were female and the mean (SD) age was 44.1 (13.6) years. The
mean (SD) PaO2 /FI O2 ratio at referral was 10.2 (4.1) kPa and median (IQR
[range]) Murray score was 3.25 (3.0-3.5 [1.5-4.0]). Forty-eight patients (80%)
required veno-venous extracorporeal membrane oxygenation at the referring centre.
There were no cannulation or extracorporeal membrane oxygenation-related
complications. The median (IQR [range]) retrieval distance was 47.2 (14.9-77.0
[2.3-342.0]) miles. There were no major adverse events during retrieval. Thirty
seven patients (77%) who received extracorporeal membrane oxygenation survived to
discharge from the intensive care unit and 36 patients (75%) were alive after six
months. Senior intensivist-initiated and delivered mobile extracorporeal membrane
oxygenation is safe and associated with a high incidence of survival.
PMID- 25850688
TI - Guns, Impulsive Angry Behavior, and Mental Disorders: Results from the National
Comorbidity Survey Replication (NCS-R).
AB - Analyses from the National Comorbidity Study Replication provide the first
nationally representative estimates of the co-occurrence of impulsive angry
behavior and possessing or carrying a gun among adults with and without certain
mental disorders and demographic characteristics. The study found that a large
number of individuals in the United States self-report patterns of impulsive
angry behavior and also possess firearms at home (8.9%) or carry guns outside the
home (1.5%). These data document associations of numerous common mental disorders
and combinations of angry behavior with gun access. Because only a small
proportion of persons with this risky combination have ever been involuntarily
hospitalized for a mental health problem, most will not be subject to existing
mental health-related legal restrictions on firearms resulting from a history of
involuntary commitment. Excluding a large proportion of the general population
from gun possession is also not likely to be feasible. Behavioral risk-based
approaches to firearms restriction, such as expanding the definition of gun
prohibited persons to include those with violent misdemeanor convictions and
multiple DUI convictions, could be a more effective public health policy to
prevent gun violence in the population.
PMID- 25850690
TI - Schizotypal, Dissociative, and Imaginative Processes in a Clinical OCD Sample.
AB - OBJECTIVE: Previous research in a nonclinical sample has suggested that
schizotypal, dissociative, and imaginative processes may play a role in obsessive
compulsive disorder (OCD) symptoms (Aardema & Wu, ). The present study aims to
extend these findings in a clinical sample. METHOD: N = 75 adults (mean age =
37.99; 61.3% female), meeting the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, Text Revision, diagnostic criteria for OCD completed a
battery of self-report questionnaires measuring schizotypal, dissociative, and
imaginative processes. RESULTS: Hierarchical regression analyses revealed
inferential confusion and dissociation to be the strongest predictors of OCD
symptoms, replicating and extending the findings by Aardema and Wu ().
CONCLUSION: Results support the notion that inferential confusion and
dissociation are important variables to consider in understanding symptoms of OCD
independently from obsessive beliefs and negative mood states.
PMID- 25850691
TI - Difficulty in obtaining travel insurance after cancer.
PMID- 25850689
TI - Modulation of the host innate immune and inflammatory response by translocated
bacterial proteins.
AB - Bacterial secretion systems play a central role in interfering with host
inflammatory responses to promote replication in tissue sites. Many intracellular
bacteria utilize secretion systems to promote their uptake and survival within
host cells. An intracellular niche can help bacteria avoid killing by phagocytic
cells, and may limit host sensing of bacterial components. Secretion systems can
also play an important role in limiting host sensing of bacteria by translocating
proteins that disrupt host immune signalling pathways. Extracellular bacteria, on
the other hand, utilize secretion systems to prevent uptake by host cells and
maintain an extracellular niche. Secretion systems, in this case, limit sensing
and inflammatory signalling which can occur as bacteria replicate and release
bacterial products in the extracellular space. In this review, we will cover the
common mechanisms used by intracellular and extracellular bacteria to modulate
innate immune and inflammatory signalling pathways, with a focus on translocated
proteins of the type III and type IV secretion systems.
PMID- 25850692
TI - Regulatory T cells: Mechanisms of suppression and impairment in autoimmune liver
disease.
AB - There are three classic liver diseases with probable autoimmune etiology: primary
biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. The
occurrence of these autoimmune conditions is determined by the breakdown of
immune-regulatory mechanisms that in health are responsible for maintaining
immunological tolerance against self-antigens. Among the multiple T cell subsets
with suppressive function, the regulatory T cells (Tregs), defined by the
expression of CD4, the IL-2 receptor alpha chain (CD25), and the transcription
factor FOXP3, have emerged as having a central role in maintaining immune
tolerance to autoantigens. Tregs are equipped with an array of mechanisms of
suppression, including the modulation of antigen presenting cell maturation and
function, the killing of target cells, the disruption of metabolic pathways, and
the production of anti-inflammatory cytokines. In all the three autoimmune liver
diseases mentioned above, there is evidence pointing for either a reduced
frequency and/or function of Tregs. Here, we review the definition, phenotypic
characteristics, and mechanisms of suppression employed by Tregs and then we
discuss the evidence available pointing to their impairment in patients with
autoimmune liver disease.
PMID- 25850693
TI - A novel polymeric drug delivery system for localized and sustained release of
tacrolimus (FK506).
AB - Despite substantial improvement in microsurgical techniques for nerve repair,
recovery after peripheral nerve injury is usually incomplete. FK506, an FDA
approved immunosuppressant, improves functional recovery and reinnervation
following peripheral nerve injury in animal models. However, systemically
delivered FK506 causes undesirable global immunosuppression. We have, therefore,
engineered a biodegradable local delivery system for FK506 using fibrin gel as a
drug reservoir that could be placed at a site of nerve injury. FK506 was
incorporated into fibrin gel in solubilized, particulated, and poly(lactic-co
glycolic) acid (PLGA) microspheres-encapsulated forms. A tunable release of FK506
in the fibrin gel from days to weeks was observed with the rate of release being
most rapid for the solubilized form and then the particulate form. The most
prolonged period of release was seen with the PLGA microsphere-encapsulated form.
As analyzed by in vitro dorsal root ganglion (DRG) neurite extension assay, PLGA
microsphere encapsulation of FK506 did not alter the drug's properties and the
released FK506 maintained its bioactivity over the entire period of release. This
study suggests that local delivery of FK506 with fibrin hydrogel could be used to
enhance peripheral nerve regeneration.
PMID- 25850694
TI - Bacterial cellulose-hydroxyapatite composites with osteogenic growth peptide
(OGP) or pentapeptide OGP on bone regeneration in critical-size calvarial defect
model.
AB - This study aimed to evaluate the potential of bacterial cellulose-hydroxyapatite
(BC-HA) composites associated with osteogenic growth peptide (OGP) or
pentapeptide OGP(10-14) in bone regeneration in critical-size calvarial defects
in mice. In this study, the BC-HA, BC-HA-OGP, and BC-HA-OGP(10-14) membranes were
analyzed at 3, 7, 15, 30, 60, and 90 days. In each period, the specimens were
evaluated by micro-computed tomography (uCT), descriptive histology, gene
expression of bone biomarkers by qPCR and VEGFR-2 (vascular endothelial growth
factor) quantification by ELISA. Three days post-operative, Runx2, Tnfrsf11b and
Bglap bone biomarkers were upregulated mainly by BC-HA OGP and BC-HA OGP(10-14)
membranes, suggesting an acceleration of the osteoblast differentiation/activity
with the use of these biomaterials. At 60 and 90 days, a high percentage of bone
formation was observed by uCT for BC-HA and BC-HA OGP(10-14) membranes. High
expression of some bone biomarkers, such as Alpl, Spp1, and Tnfrsf11b, was also
observed for the same membranes on days 60 and 90. In conclusion, the BC-HA
membrane promoted a better bone formation in critical-size mice calvarial
defects. Nevertheless, incorporation of the peptides at the concentration of 10(
9) mol L(-1) did not improve bone regeneration potential in the long-term.
PMID- 25850695
TI - Risk Factors for Severe Hand-Foot-Mouth Disease in Children in Hainan, China,
2011-2012.
AB - The incidence of severe/fatal cases of hand-foot-mouth disease (HFMD) has
increased in South Asia. In China, Hainan Province had the highest incidence of
mortality associated with HFMD in 2011. This study investigated the risk factors
for severe HFMD in Hainan. The HFMD survey database for Hainan Province for 2011
and 2012 was analyzed, and the biological and behavioral characteristics of
severe (n = 980) and nonsevere (n = 1679) HFMD were compared. The association
between each explanatory variable and the severity of HFMD was investigated using
a logistic regression model after adjusting for confounders. Human enterovirus 71
infection, a peak body temperature >39 degrees C, living outside urban areas,
visiting a village clinic, low birth weight, never breastfed, cared for by
grandparents, and caregiver with <6 years of education were associated with
severe HFMD. Individual characteristics that are generally shared by children in
households of low socioeconomic status tended to increase the risk of severe
HFMD.
PMID- 25850696
TI - Pathological findings and diagnostic implications of a rhesus macaque (Macacca
mulatta) model of aerosol exposure to Burkholderia mallei (glanders).
AB - Burkholderia mallei is a Gram-negative bacillus that causes a pneumonic disease
known as glanders in equids and humans, and a lymphatic infection known as farcy,
primarily in equids. With the potential to infect humans by the respiratory
route, aerosol exposure can result in severe, occasionally fatal, pneumonia.
Today, glanders infections in humans are rare, likely due to less frequent
contact with infected equids than in the past. Acutely ill humans often have non
specific clinical signs and in order to diagnose cases, especially in scenarios
of multiple cases in an unexpected setting, rapid diagnostics for B. mallei may
be critical. The pathogenesis of acute glanders in the rhesus macaque (Macaca
mulatta) was studied as an initial effort to improve diagnostic methods. In the
study described here, the diagnostic techniques of PCR, culture and
histopathology were compared. The results indicated that PCR may provide rapid,
non-invasive diagnosis of glanders in some cases. As expected, PCR results were
positive in lung tissue in 11/12 acutely infected rhesus macaques, but more
importantly in terms of diagnostic algorithm development, PCR results were
frequently positive in non-invasive samples such as broncho-alveolar lavage or
nasal swabs (7/12) and occasionally in blood (3/12). However, conventional
bacterial culture failed to recover bacteria in many of these samples. The study
showed that the clinical presentation of aerosol-exposed rhesus macaques is
similar to descriptions of human glanders and that PCR has potential for rapid
diagnosis of outbreaks, if not individual cases.
PMID- 25850697
TI - ASSOCIATIONS BETWEEN ULTRASOUND AND CLINICAL FINDINGS IN 87 CATS WITH URETHRAL
OBSTRUCTION.
AB - Urethral obstruction is a life-threatening form of feline lower urinary tract
disease. Ultrasonographic risk factors for reobstruction have not been previously
reported. Purposes of this retrospective cross-sectional study were to describe
urinary tract ultrasound findings in cats following acute urethral obstruction
and determine whether ultrasound findings were associated with reobstruction.
Inclusion criteria were a physical examination and history consistent with
urethral obstruction, an abdominal ultrasound including a full evaluation of the
urinary system within 24 h of hospitalization, and no cystocentesis prior to
ultrasound examination. Medical records for included cats were reviewed and
presence of azotemia, hyperkalemia, positive urine culture, and duration of
hospitalization were recorded. For medically treated cats with available outcome
data, presence of reobstruction was also recorded. Ultrasound images were
reviewed and urinary tract characteristics were recorded. A total of 87 cats met
inclusion criteria. Common ultrasound findings for the bladder included echogenic
urine sediment, bladder wall thickening, pericystic effusion, hyperechoic
pericystic fat, and increased urinary echoes; and for the kidneys/ureters
included pyelectasia, renomegaly, perirenal effusion, hyperechoic perirenal fat,
and ureteral dilation. Six-month postdischarge outcomes were available for 61
medically treated cats and 21 of these cats had reobstruction. No findings were
associated with an increased risk of reobstruction. Ultrasonographic perirenal
effusion was associated with severe hyperkalemia (P = 0.009, relative risk 5.75,
95% confidence interval [1.54-21.51]). Findings supported the use of ultrasound
as an adjunct for treatment planning in cats presented with urethral obstruction
but not as a method for predicting risk of reobstruction.
PMID- 25850698
TI - Low-dose RUTF protocol and improved service delivery lead to good programme
outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar.
AB - The treatment of uncomplicated severe acute malnutrition (SAM) requires
substantial amounts of ready-to-use therapeutic food (RUTF). In 2009, Action
Contre la Faim anticipated a shortfall of RUTF for their nutrition programme in
Myanmar. A low-dose RUTF protocol to treat children with uncomplicated SAM was
adopted. In this protocol, RUTF was dosed according to beneficiary's body weight,
until the child reached a Weight-for-Height z-score of >=-3 and mid-upper arm
circumference >=110 mm. From this point, the child received a fixed quantity of
RUTF per day, independent of body weight until discharge. Specific measures were
implemented as part of this low-dose RUTF protocol in order to improve service
quality and beneficiary support. We analysed individual records of 3083 children
treated from July 2009 to January 2010. Up to 90.2% of children recovered, 2.0%
defaulted and 0.9% were classified as non-responders. No deaths were recorded.
Among children who recovered, median [IQR] length of stay and weight gain were 42
days [28; 56] and 4.0 g kg(-1) day(-1) [3.0; 5.7], respectively. Multivariable
logistic regression showed that children older than 48 months had higher odds of
non-response to treatment than younger children (adjusted odds ratio: 3.51, 95%
CI: 1.67-7.42). Our results indicate that a low-dose RUTF protocol, combined with
specific measures to ensure good service quality and beneficiary support, was
successful in treating uncomplicated SAM in this setting. This programmatic
experience should be validated by randomised studies aiming to test, quantify and
attribute the effect of the protocol adaptation and programme improvements
presented here.
PMID- 25850699
TI - Early and late maternal effects on hatching phenology of Heterocypris incongruens
(Crustacea: Ostracoda).
AB - In ephemeral ponds, the hatching asynchrony of resting eggs may be adaptive and
the result of a maternal bet-hedging strategy. A mother can influence the progeny
phenology through conditions experienced during life cycle even in early
development stages. We investigated the consequences of a hatching delay for
offspring and compared early and late maternal effects in a clonal lineage of
Heterocypris incongruens. We used females from genetically identical, 40 months
old, resting eggs that hatched, asynchronically, after a first (FI) or a second
(SI) inundation event. Maternal origin (FI or SI) was considered an early effect
involving the maternal response to hatching stimuli during the embryological
dormant stage. Maternal age at deposition and egg size were considered late
effects that account for maternal conditions during active stage. We compared
size and development time of eggs produced by FI and SI females under laboratory
condition (24 degrees C 12:12 L:D photoperiod). Maternal origin affected
development time to adulthood which was later in FI than in SI females, and
fecundity that was higher in FI than in SI females. SI eggs were smaller than FI
eggs: size was affected by maternal age at deposition and was directly related to
the egg development time. Development time varied from 1 to 117 days and was
shorter in SI eggs than in FI eggs. Our results showed that maternal response
during embryological stage affects the performance in successive active stages
and suggested that hatching asynchrony may be considered a risk spread strategy.
PMID- 25850700
TI - Determinants of elite-level air rifle shooting performance.
AB - This study focused on identifying the most important factors determining
performance in elite-level air rifle shooting technique. Forty international- and
national-level shooters completed a simulated air rifle shooting competition
series. From a total of 13 795 shots in 319 tests, shooting score and 17 aiming
point trajectory variables were measured with an optoelectronic device and six
postural balance variables were measured with force platform. Principal component
analysis revealed six components in the air rifle shooting technique: aiming
time, stability of hold, measurement time, cleanness of triggering, aiming
accuracy, and timing of triggering. Multiple regression analysis identified four
of those, namely stability of hold, cleanness of triggering, aiming accuracy, and
timing of triggering as the most important predictors of shooting performance,
accounting for 81% of the variance in shooting score. The direct effect of
postural balance on performance was small, accounting for less than 1% of the
variance in shooting score. Indirectly, the effect can be greater through a more
stable holding ability, to which postural balance was correlated significantly (R
= 0.55, P < 0.001). The results of the present study can be used in assessing
athletes' technical strengths and weaknesses and in directing training programs
on distinct shooting technical components.
PMID- 25850701
TI - Moving droplets between closed and open microfluidic systems.
AB - In electric-field-mediated droplet microfluidics, there are two distinct
architectures - closed systems using parallel-plate electrodes and open systems
using coplanar electrodes fabricated on an open substrate. An architecture
combining both closed and open systems on a chip would facilitate many of the
chemical and biological processes now envisioned for the laboratory on a chip. To
accomplish such an integration requires a means to move droplets back and forth
between the two. This paper presents an investigation of the requirements for
such manipulation of both water and oil droplets. The required wetting conditions
for a droplet to cross the open/closed boundary is revealed by a force balance
analysis and predictions of this model are compared to experimental results.
Water droplets can be moved between closed and open systems by electrowetting
actuation; droplet detachment from the upper plate is facilitated by the use of
beveled edge. The force model predicts that driving an oil droplet from a closed
to an open structure requires an oleophobic surface. This prediction has been
tested and confirmed using <100> silicon wafers made oleophobic by re-entrant
microstructures etched into the surface.
PMID- 25850702
TI - Biocompatible capped iron oxide nanoparticles for Vibrio cholerae detection.
AB - We report the studies relating to fabrication of an efficient immunosensor for
Vibrio cholerae detection. Magnetite (iron oxide (Fe(3)O(4))) nanoparticles (NPs)
have been synthesized by the co-precipitation method and capped by citric acid
(CA). These NPs were electrophoretically deposited onto indium-tin-oxide (ITO)
coated glass substrate and used for immobilization of monoclonal antibodies
against Vibrio cholerae (Ab) and bovine serum albumin (BSA) for Vibrio cholerae
detection using an electrochemical technique. The structural and morphological
studies of Fe(3)O(4) and CA-Fe(3)O(4)/ITO were characterized by x-ray diffraction
(XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR)
spectroscopy, and dynamic light scattering (DLS) techniques. The average
crystalline size of Fe(3)O(4), CA-Fe(3)O(4) nanoparticles obtained were about 29
+/- 1 nm and 37 +/- 1 nm, respectively. The hydrodynamic radius of the
nanoparticles was found to be 77.35 nm (Fe(3)O(4)) and 189.51 nm (CA-Fe(3)O(4))
by DLS measurement. The results of electrochemical response studies of the
fabricated BSA/Ab/CA-Fe(2)O(3)/ITO immunosensor exhibits a good detection range
of 12.5-500 ng mL(-1) with a low detection limit of 0.32 ng mL(-1), sensitivity
0.03 Omega/ng ml(-1) cm(-2), and reproducibility more than 11 times.
PMID- 25850703
TI - Relationship of Structural Characteristics to Biomechanical Profile in Normal,
Keratoconic, and Crosslinked Eyes.
AB - PURPOSE: To evaluate the correlation of corneal biomechanical parameters with
structural characteristics in normal, keratoconic, and collagen crosslinked eyes.
METHODS: A prospective observational study that included 50 normal, 100
keratoconic, and 25 crosslinked eyes. All eyes were imaged using a Scheimpflug
camera and an ocular response analyzer. The main outcome measures analyzed were
central corneal thickness (CCT), corneal volume (CV), maximal keratometry (Kmax),
corneal hysteresis (CH), and corneal resistance factor (CRF). RESULTS:
Significant differences were noted among all 3 groups of eyes for CCT, CV, Kmax,
CH, and CRF values (P < 0.05 by analysis of variance). CH and CRF correlated
negatively (CH, r = -0.40; CRF, r = -0.44; both P < 0.0001) with the Pentacam
topographic keratoconus classification. Both CH and CRF correlated positively
with CCT and CV for the normal, keratoconic, and crosslinked eyes. In contrast,
significant negative correlations were observed between CH, CRF, and Kmax in the
keratoconic eyes (CH, r = -0.43; CRF, r = -0.53; both P < 0.0001), whereas no
association was noted for the normal and crosslinked eyes. CONCLUSIONS: CH and
CRF are influenced by the corneal structure, with higher values noted in corneas
with greater thickness and volume. Corneal biomechanical parameters progressively
decrease as the severity of keratoconus increases. After collagen crosslinking,
the relationship of the corneal curvature to the biomechanical profile is similar
to normal eyes.
PMID- 25850704
TI - Calcified corneal nerves.
AB - PURPOSE: To report a case of calcified corneal nerves in an eye with long
standing diabetic eye disease. METHODS: This is a case report where the clinical
diagnosis was made using a slit-lamp biomicroscope and confirmed using in vivo
confocal microscopy. Photoslit-lamp images were taken for both eyes, and nerve
thickness measurements made using ImageJ software. RESULTS: A 70-year-old British
white woman showed band keratopathy in the right eye and dense white lines and
dots in her left cornea on slit-lamp examination. The left corneal images had an
appearance exactly similar to stromal nerves and terminal bulbs reported before.
In vivo confocal microscopy (IVCM) of the left cornea showed hyperreflective and
thickened stromal and sub-Bowman nerves and their characteristic termination in
bulbous thickenings. CONCLUSIONS: Clinically detected corneal nerve calcification
has not been described before. This report presents the direct visualization of
calcified corneal nerves and their terminal bulbs and IVCM characteristics.
PMID- 25850705
TI - Novel corneal piggyback technique for consecutive intraocular lens implantation
and penetrating keratoplasty surgery.
AB - PURPOSE: To report a novel "piggyback" penetrating keratoplasty technique
performed in a patient with severe keratoconus. METHODS: A 43-year-old man
underwent cataract surgery and a new "piggyback" penetrating keratoplasty (PKP)
technique in his right eye, as he suffered from severe keratoconus and mature
cataract due to severe atopic dermatitis. Under general anesthesia,
phacoemulsification and aspiration (PEA), intraocular lens (IOL) implantation,
and "piggyback" PKP while avoiding open-sky surgery was performed to prevent
serious complications including IOL and vitreous prolapse. This PKP technique had
been completed as a totally closed surgery. RESULTS: One year after "piggyback"
PKP and cataract surgery, the grafted cornea remained clear and IOL was also well
positioned. Best-corrected visual acuity improved from hand motions to 30/100.
CONCLUSIONS: A novel "piggyback" PKP technique was successfully performed in a
patient with severe keratoconus. The new "piggyback" corneal transplantation
technique may become an indispensable tool for transplant surgeons who want to
improve surgical safety and predictability.
PMID- 25850706
TI - Cornea preservation time study: methods and potential impact on the cornea donor
pool in the United States.
AB - PURPOSE: The aim of this study was to describe the aims, methods, donor and
recipient cohort characteristics, and potential impact of the Cornea Preservation
Time Study (CPTS). METHODS: The CPTS is a randomized clinical trial conducted at
40 clinical sites (70 surgeons) designed to assess the effect of donor cornea
preservation time (PT) on graft survival 3 years after Descemet stripping
automated endothelial keratoplasty (DSAEK). Eyes undergoing surgery for Fuchs
endothelial corneal dystrophy or pseudophakic/aphakic corneal edema were
randomized to receive donor corneas stored <=7 days or 8 to 14 days. Donor and
patient characteristics, tissue preparation and surgical parameters, recipient
and donor corneal stroma clarity, central corneal thickness, intraocular
pressure, complications, and a reading center-determined central endothelial cell
density were collected. Surveys were conducted to evaluate pre-CPTS PT practices.
RESULTS: The 1330 CPTS donors were: 49% >60 years old, 27% diabetic, had a median
eye bank-determined screening endothelial cell density of 2688 cells/mm, and 74%
eye bank prepared for DSAEK. A total of 1090 recipients (1330 eyes including 240
bilateral cases) had: median age of 70 years, were 60% female, 90% white, 18%
diabetic, 52% phakic, and 94% had Fuchs endothelial corneal dystrophy. Before the
CPTS, 19 eye banks provided PT data on 20,852 corneas domestically placed for
DSAEK in 2010 to 2011; 96% were preserved <=7 days. Of 305 American Academy of
Ophthalmology members responding to a pre-CPTS survey, 233 (76%) set their
maximum PT preference at 8 days or less. CONCLUSIONS: The CPTS will increase
understanding of factors related to DSAEK success and, if noninferiority of
longer PT is shown, will have great potential to extend the available pool of
endothelial keratoplasty donors.Clinical Trial Registration-URL:
http://www.clinicaltrials.gov. Unique identifier: NCT01537393.
PMID- 25850707
TI - Sutureless anterior lamellar keratoplasty with phacoemulsification.
AB - PURPOSE: To compare the results of microkeratome-assisted sutureless anterior
lamellar keratoplasty (SALK) with and without phacoemulsification. METHODS: In
this retrospective comparative interventional case series, patients with
superficial anterior corneal opacity were divided into 2 groups. Eyes in group 1
(n = 6) had associated cataract and underwent SALK with phacoemulsification
surgery (SALK triple). Eyes in group 2 (n = 6) did not have cataract and
underwent only anterior lamellar keratoplasty. A 200-MUm microkeratome head was
used for host and donor cut. Fibrin glue was applied at the graft-host junction.
Visual acuity, refractive error, topographic changes, and pachymetry were noted.
RESULTS: Mean follow-up was 9 +/- 2.7 months. The best spectacle-corrected visual
acuity (BSCVA) improved significantly over the preoperative value in both the
groups at 1 month, 6 months, and the last follow-up (P = 0.028). The mean gain in
BSCVA was 8.8 +/- 3.4 lines and 6.8 +/- 5.2 lines, respectively, for groups 1 and
2 at the last follow-up, with no statistically significant difference in the
BSCVA of both groups at the last follow-up (P = 0.80). There was no statistical
difference at the last follow-up between the 2 groups with respect to spherical
equivalent (P = 0.6), cylinder (P = 0.81), topographic astigmatism (P = 0.75),
and graft thickness (P = 0.81). One patient in group 1 underwent graft rejection,
which completely reversed with treatment. No cases of graft dislocation,
infection, epithelial ingrowth, vascularization, or recurrence of primary
pathology were noted in either group. CONCLUSIONS: SALK triple is an effective
surgery for early visual rehabilitation of patients with superficial anterior
corneal opacity and concomitant cataract.
PMID- 25850708
TI - Prospective Randomized Trial Comparing Efficacy of Topical Loteprednol Etabonate
0.5% Versus Cyclosporine-A 0.05% for Treatment of Dry Eye Syndrome Following
Hematopoietic Stem Cell Transplantation.
AB - PURPOSE: To evaluate the safety and efficacy of topical loteprednol etabonate
(LE) 0.5% compared with cyclosporine A (CsA) 0.05% for the prophylaxis and
treatment of dry eye syndrome (DES) after hematopoietic stem cell transplantation
(HSCT). METHODS: Seventy-five patients were randomized to LE (n = 76 eyes of 38
patients) or CsA (n = 74 eyes of 37 patients) pre-HSCT. Lissamine green and
fluorescein staining, tear break-up time, tear osmolarity (Osm), Schirmer score
(Sch), intraocular pressure, visual acuity, and Ocular Surface Disease Index were
assessed pre-HSCT, 3, 6, 9, and 12 months post-HSCT. RESULTS: There were no
differences in DES incidence (P = 0.22; log-rank test) or progression (P = 0.41;
log-rank test) between the 2 treatment arms during the course of the study. Among
eyes with no DES at enrollment, the Kaplan-Meier analysis yielded a 90% rate of
DES development in cyclosporine-treated eyes and a 79% rate of DES development in
LE-treated eyes by 12 months post-HSCT. The Kaplan-Meier analysis of eyes with
DES at enrollment demonstrated a 38% rate of disease progression among
cyclosporine-treated eyes and a 26% rate of disease progression among loteprednol
treated eyes by 12 months. No patient in either group had an elevation of 10 mm
Hg or greater from baseline at any study visit, and no patients had their
treatment discontinued for elevation in intraocular pressure. CONCLUSIONS: Pre
HSCT initiation of LE 0.5% appears to be safe and may be as effective as CsA 0.5%
for the treatment and prophylaxis of DES following HSCT.
PMID- 25850709
TI - Vitamin D versus placebo in improvement of endothelial dysfunction: a meta
analysis of randomized clinical trials.
AB - AIMS: The possible effect of vitamin D administration in humans on endothelial
dysfunction (ED) still remains undetermined. The current meta-analysis was
performed to evaluate if vitamin D could improve ED. METHODS: Randomized, double
blind, and placebo-controlled clinical trials were identified by systematic
search of the PubMed, the Cochrane Library, the Web of Science and the Scopus
data bases, as well as different reviews and clinical trials articles. A random
effects model was used to calculate the pooled overall effect on flow-mediated
dilation (FMD) linked to the vitamin D administration. Meta-regression and
subgroup analyses were performed to evaluate the impact of study characteristics
on the effect of vitamin D administration on FMD. RESULTS: A total of eight
studies with nine relevant study arms were identified. The obtained results of
pooled analysis showed that vitamin D administration did not improve FMD (eight
studies, 529 subjects; weighted mean difference (WMD): 0.96%, 95% CI: -1.24% to
2.06%; P = 0.09). This was probably due to significant heterogeneity in between
included trials (I(2) = 84%, P < 0.00001). On the other hand, subgroup analysis
demonstrated that vitamin D improved FMD in trials that lasted <16 weeks; if
systolic blood pressure (SBP) was higher than 140 mmHg and in trials where
diastolic blood pressure (DBP) was <80 mmHg. CONCLUSION: Although the current
evidence clearly demonstrates that in certain conditions vitamin D can improve
ED, a larger number of clinical trials are needed to confirm this assumption to
confirm or reject the final statement on this topic.
PMID- 25850712
TI - Type 2 diabetes mellitus treatment patterns in U.S. nursing home residents.
AB - BACKGROUND: The prevalence of type 2 diabetes mellitus (diabetes) in nursing home
residents (NHRs) is increasing, concurrently with obesity and other comorbid
conditions. NHR would benefit greatly from antidiabetic medications that would
improve glycemic control and give a lower risk of hypoglycemia but that do not
contribute to weight gain in obese individuals. OBJECTIVE: To examine the
prescription patterns to NHRs with diabetes, including the use of newer
injectable therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists.
METHODS: Treatment patterns of diabetes in NHR were analyzed using Minimum Data
Set records and prescription claims from the Omnicare Senior Health Outcomes data
repository (May 2011-September 2012). RESULTS: The prevalence of diabetes in this
population of 229,283 NHRs was 35.4%. Among the 44,665 NHRs with diabetes and
prescription claims data, the prevalence of obesity (40.3%) and multiple
comorbidities (100%) was high. Approximately 20% of the NHRs with diabetes were
aged <65 years. Overall, 20% of NHRs had diabetes that was untreated with
medications during the study period. Insulin was the mainstay of treatment
(>80%), followed by oral agents (54%). GLP-1 receptor agonist use was low (0.5%)
and associated with poor treatment persistence. CONCLUSION: Considerations other
than glycemic control may drive prescribing decisions, contrary to
recommendations from the American Diabetes Association, American Medical
Directors Association, and European Association for the Study of Diabetes.
PMID- 25850710
TI - Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in
murine RyR2-P2328S hearts.
AB - AIMS: Cardiac ryanodine receptor mutations are associated with catecholaminergic
polymorphic ventricular tachycardia (CPVT), and some, including RyR2-P2328S, also
predispose to atrial fibrillation. Recent work associates reduced atrial Nav 1.5
currents in homozygous RyR2-P2328S (RyR2(S/S) ) mice with slowed conduction and
increased arrhythmogenicity. Yet clinically, and in murine models, the Nav 1.5
blocker flecainide reduces ventricular arrhythmogenicity in CPVT. We aimed to
determine whether, and how, flecainide influences atrial arrhythmogenicity in
RyR2(S/S) mice and their wild-type (WT) littermates. METHODS: We explored effects
of 1 MUm flecainide on WT and RyR2(S/S) atria. Arrhythmic incidence, action
potential (AP) conduction velocity (CV), atrial effective refractory period
(AERP) and AP wavelength (lambda = CV * AERP) were measured using multi-electrode
array recordings in Langendorff-perfused hearts; Na(+) currents (INa ) were
recorded using loose patch clamping of superfused atria. RESULTS: RyR2(S/S)
showed more frequent atrial arrhythmias, slower CV, reduced INa and unchanged
AERP compared to WT. Flecainide was anti-arrhythmic in RyR2(S/S) but pro
arrhythmic in WT. It increased INa in RyR2(S/S) atria, whereas it reduced INa as
expected in WT. It increased AERP while sparing CV in RyR2(S/S) , but reduced CV
while sparing AERP in WT. Thus, RyR2(S/S) hearts have low lambda relative to WT;
flecainide then increases lambda in RyR2(S/S) but decreases lambda in WT.
CONCLUSIONS: Flecainide (1 MUm) rescues the RyR2-P2328S atrial arrhythmogenic
phenotype by restoring compromised INa and lambda, changes recently attributed to
increased sarcoplasmic reticular Ca(2+) release. This contrasts with the
increased arrhythmic incidence and reduced INa and lambda with flecainide in WT.
PMID- 25850711
TI - Dynasore enhances the formation of mitochondrial antiviral signalling aggregates
and endocytosis-independent NF-kappaB activation.
AB - BACKGROUND AND PURPOSE: Dynasore has been used extensively as an inhibitor of
clathrin-mediated endocytosis. While studying the role of endocytosis in LPS
induced signalling events, we discovered that dynasore itself induced activation
of NF-kappaB, independently of its effects on endocytosis and without involving
the Toll-like receptor 4 signalling pathways. The purpose of this study was to
characterize this novel effect and to explore the underlying mechanism of action.
EXPERIMENTAL APPROACH: We utilized gel electrophoresis, microscopy, gene
knockdown and luciferase-based promoter activity to evaluate the effect of
dynasore on cell signalling pathways and to delineate the mechanisms involved in
its effects, KEY RESULTS: Dynasore activated the NF-kappaB and IFN-beta pathways
by activating mitochondrial antiviral signalling protein (MAVS). We showed that
MAVS is activated by NOX/Rac and forms high molecular weight aggregates, similar
to that observed in response to viral infection. We also demonstrated that
dynasore-induced activation of JNK occurs downstream of MAVS and is required for
activation of NF-kappaB and IFN-beta. CONCLUSION AND IMPLICATIONS: These findings
demonstrate a novel effect of dynasore on cell signalling. We describe a novel
Rac1-, ROS- and MAVS-mediated signalling cascade through which dynasore
dramatically activates NF-kappaB, mimicking the viral induction of this key
inflammatory signalling pathway. Our results call attention to the need for a
broader interpretation of results when dynasore is used in its traditional
fashion as an inhibitor of clathrin-mediated endocytosis. These results suggest
the intriguing possibility that dynasore or one of its analogues might be of
value as an antiviral therapeutic strategy or vaccine adjuvant.
PMID- 25850713
TI - Farm to Fork Quantitative Risk Assessment of Listeria monocytogenes Contamination
in Raw and Pasteurized Milk Cheese in Ireland.
AB - The objective of this study was to model and quantify the level of Listeria
monocytogenes in raw milk cheese (RMc) and pasteurized milk cheese (PMc) from
farm to fork using a Bayesian inference approach combined with a quantitative
risk assessment. The modeling approach included a prediction of contamination
arising from the farm environment as well from cross-contamination within the
cheese-processing facility through storage and subsequent human exposure. The
model predicted a high concentration of L. monocytogenes in contaminated RMc
(mean 2.19 log10 CFU/g) compared to PMc (mean -1.73 log10 CFU/g). The mean
probability of illness (P1 for low-risk population, LR) and (P2 for high-risk
population, HR, e.g., immunocompromised) adult Irish consumers following exposure
to contaminated cheese was 7 * 10(-8) (P1 ) and 9 * 10(-4) (P2 ) for RMc and 7 *
10(-10) (P1 ) and 8 * 10(-6) (P2 ) for PMc, respectively. In addition, the model
was used to evaluate performance objectives at various stages, namely, the cheese
making and ripening stages, and to set a food safety objective at the time of
consumption. A scenario analysis predicted various probabilities of L.
monocytogenes contamination along the cheese-processing chain for both RMc and
PMc. The sensitivity analysis showed the critical factors for both cheeses were
the serving size of the cheese, storage time, and temperature at the distribution
stage. The developed model will allow food processors and policymakers to
identify the possible routes of contamination along the cheese-processing chain
and to reduce the risk posed to human health.
PMID- 25850714
TI - Listing of plenary, oral and poster presentations of the 36th annual meeting of
the american brachytherapy society.
PMID- 25850715
TI - Decreasing Transmembrane Segment Length Greatly Decreases Perfringolysin O Pore
Size.
AB - Perfringolysin O (PFO) is a transmembrane (TM) beta-barrel protein that inserts
into mammalian cell membranes. Once inserted into membranes, PFO assembles into
pore-forming oligomers containing 30-50 PFO monomers. These form a pore of up to
300 A, far exceeding the size of most other proteinaceous pores. In this study,
we found that altering PFO TM segment length can alter the size of PFO pores. A
PFO mutant with lengthened TM segments oligomerized to a similar extent as wild
type PFO, and exhibited pore-forming activity and a pore size very similar to
wild-type PFO as measured by electron microscopy and a leakage assay. In
contrast, PFO with shortened TM segments exhibited a large reduction in pore
forming activity and pore size. This suggests that the interaction between TM
segments can greatly affect the size of pores formed by TM beta-barrel proteins.
PFO may be a promising candidate for engineering pore size for various
applications.
PMID- 25850716
TI - Cross-beta Amyloid Nanohybrids Loaded With Cytochrome C Exhibit Superactivity in
Organic Solvents.
AB - The present study reports the development of a unique class of Cytochrome C
(CytC)-loaded cross-beta amyloid nanohybrids. The peroxidase activity of the
bound CytC increased up to two orders of magnitude in organic solvents compared
to the activity of unbound CytC in water. The amyloid sequences used in the study
feature the nucleating core (17) LVFF(21) of the beta amyloid (Abeta), which
assembled to form homogenous fibers and nanotubes. The morphology and exposed
surface of the amyloid nanohydrids critically modulated the CytC activity. A CytC
Ac-KLVFFAE-NH2 hybrid featuring nanofiber morphology showed 308-fold higher
activity than unbound CytC in water, which increased to 450-fold with the
nanotube morphology of CytC-Ac-KLVFFAL-NH2 . Notably, activity declined
substantially when the exposed surface charge was detuned by replacing lysine
with histidine, thus underpinning the importance of surface charge. This enzyme
amyloid nanohybrid system could facilitate the technological application of
enzymes.
PMID- 25850717
TI - Radiosynthesis and evaluation of 18F-labeled aliphatic phosphonium cations as a
myocardial imaging agent for positron emission tomography.
AB - INTRODUCTION: Lipophilic cations such as phosphonium cations penetrate the
hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in
the mitochondria in response to negative inner-transmembrane potentials. The
present study reports the radiosynthesis and evaluation of (18)F-labeled
aliphatic triphenylphosphonium cations as a potential agent for myocardial
imaging by using PET. MATERIALS AND METHODS: (7
[(18)F]fluoroheptyl)triphenylphosphonium salt ([(18)F]3) and (8
[(18)F]fluorooctyl)triphenylphosphonium salt ([(18)F]6) were radiolabeled by
means of two-step nucleophilic substitution reactions. We measured the log P
value of [(18)F]3 and [F]6 to assess the appropriate range of lipophilicity for
their suitability as PET myocardial imaging agents. Normal rats were imaged with
microPET after intravenous injection of 37 MBq of [(18)F]3 and [(18)F]6. To
determine the pharmacokinetics, a region of interest was drawn around the heart,
and time-activity curves of [(18)F]3 and [(18)F]6 were generated to obtain the
counts per pixel per second. RESULTS: The radiolabeled compounds [(18)F]3 and
[(18)F]6 were synthesized with 18-25% yield. The radiochemical purity was greater
than 98% on the basis of the analytical high-performance liquid chromatography
system, and the specific activity was greater than 160-170 Ci/mmol. The log P
value of the tracers was 2.52 +/- 0.01 ([(18)F]3) and 2.91 +/- 0.02 ([(18)F]6).
Myocardium-to-liver ratios of [(18)F]3 and [(18)F]6 were 2.59 and 1.07,
respectively, 10 min after injection, whereas the myocardium-to-lung ratios were
5.57 and 3.35, respectively. In addition, [(18)F]3 and [(18)F]6 showed intense,
homogenous uptake in the myocardium. CONCLUSION: (18)F-labeled aliphatic
phosphonium cations [(18)F]3 and [(18)F]6 might have potential as novel
myocardial agents for PET and could prove useful in clinical cardiac PET/computed
tomography applications.
PMID- 25850718
TI - Low-dose CT and contrast-medium CT in hybrid PET/CT systems for oncologic
patients.
PMID- 25850719
TI - Special issue on lung disease and epigenetics. Preface.
PMID- 25850720
TI - Stable and easily accessible functional dyes: dihydrotetraazaanthracenes as
versatile precursors for higher acenes.
AB - A series of new dihydrotetraazaanthracenes and one new dihydrotetraazatetracene
as substances for applications in organoelectronic devices and as suitable
building blocks for higher azaacenes was synthesised. The condensation of
aromatic diamines with dichlorodicyanopyrazine led to these tricyclic/tetracyclic
compounds. Syntheses of N-substituted phenylenediamines were developed to enable
the introduction of multiple functional groups such as ester, amino, or nitro
groups on the chromophoric system. Relationships between the structure and the
spectroscopic properties could be derived from UV/Vis absorption and fluorescence
spectroscopy, as well as by DFT and TD-DFT calculations of molecular and
aggregate structures. The absorption spectra are dominated by pi-pi* transitions
of the single molecules, whereas aggregation needs to be taken into account to
obtain reasonable agreement between theory and experiment in certain cases.
Single-crystal X-ray analyses were carried out to examine the morphology and
solid packing effects. Finally, a dihydrotetraazaanthracene was used as a
building-block to create a mesoionic octaazapentacene.
PMID- 25850721
TI - Using Joint Interviews to Add Analytic Value.
AB - Joint interviewing has been frequently used in health research, and is the
subject of a growing methodological literature. We review this literature, and
build on it by drawing on a case study of how people make decisions about taking
statins. This highlights two ways in which a dyadic approach to joint
interviewing can add analytic value compared with individual interviewing. First,
the analysis of interaction within joint interviews can help to explicate tacit
knowledge and to illuminate the range of often hard-to-access resources that are
drawn upon in making decisions. Second, joint interviews mitigate some of the
weaknesses of interviewing as a method for studying practices; we offer a
cautious defense of the often-tacit assumption that the "naturalness" of joint
interviews strengthens their credibility as the basis for analytic inferences. We
suggest that joint interviews are a particularly appropriate method for studying
complex shared practices such as making health decisions.
PMID- 25850722
TI - Perceptions of Empowerment Within and Across Partnerships in Community-Based
Participatory Research: A Dyadic Interview Analysis.
AB - Although the concept of empowerment is a key principle of community-based
participatory research (CBPR), little is known about how academic and community
partners perceive empowerment during a CBPR process. CBPR partners' perceptions
of the process were explored using semi-structured interviews with both partners
in 10 CBPR partnerships that had completed projects addressing social
determinants of health. Dyadic interview analysis was employed to understand
dynamics within and across partnerships. Five partnerships showed no differences
in perceptions of empowerment. Four had minor discrepancies. Only one partnership
varied considerably between partners, where the community partner perceived less
empowerment regarding determining the study topic and overall control, influence,
and respect throughout the process. This article discusses implications of
findings for CBPR. Evaluating partners' perceived empowerment throughout a CBPR
project might reveal areas to adjust, as not all projects with quantifiably
successful outcomes involve processes that are successful in terms of
empowerment.
PMID- 25850723
TI - MicroRNA-155 in the Heart: The Right Time at the Right Place in the Right Cell.
PMID- 25850725
TI - MicroRNA-101 inhibits rat cardiac hypertrophy by targeting Rab1a.
AB - Cardiac hypertrophy is a primary pathological change associated with
cardiovascular diseases. Dysregulated microRNAs are frequent in cardiovascular
diseases and contribute to cardiac hypertrophy by regulating a series of targeted
genes. In this study, a rat model of cardiac hypertrophy was created by
transverse abdominal aortic constriction, and cardiomyocyte hypertrophy in
cultured neonatal rat cardiomyocytes was induced using angiotensin II (AngII) to
investigate the role of miR-101 in myocardial hypertrophy. We demonstrated that
miR-101 was downregulated in both the transverse abdominal aortic constriction
rat model and hypertrophic cardiac myocytes. The overexpression of miR-101 in
neonatal rat cardiomyocytes, which was accompanied by a reduced Rab1a level,
inhibits 3 cardinal features of cardiomyocyte hypertrophy: fetal gene expression,
protein synthesis, and cell enlargement. Conversely, the downregulation of miR
101 reverses these effects. Furthermore, the luciferase reporter system
demonstrated that Rab1a is a target gene of miR-101, and the ectopic expression
of Rab1a can reverse the cardiomyocyte hypertrophy inhibitory activity of miR
101. Taken together, our findings identify miR-101 as an important regulator in
cardiac hypertrophy and implicate the potential application of miR-101 in the
therapy of cardiac hypertrophy.
PMID- 25850724
TI - MicroRNA-155 Exerts Cell-Specific Antiangiogenic but Proarteriogenic Effects
During Adaptive Neovascularization.
AB - BACKGROUND: Adaptive neovascularization after arterial occlusion is an important
compensatory mechanism in cardiovascular disease and includes both the remodeling
of pre-existing vessels to collateral arteries (arteriogenesis) and angiogenic
capillary growth. We now aimed to identify regulatory microRNAs involved in the
modulation of neovascularization after femoral artery occlusion in mice. METHODS
AND RESULTS: Using microRNA-transcriptome analysis, we identified miR-155 as a
downregulated microRNA during hindlimb ischemia. Correspondingly, inhibition of
miR-155 in endothelial cells had a stimulatory effect on proliferation and
angiogenic tube formation via derepression of its direct target gene angiotensin
II type 1 receptor. Surprisingly, miR-155-deficient mice showed an unexpected
phenotype in vivo, with a strong reduction of blood flow recovery after femoral
artery ligation (arteriogenesis) dependent on the attenuation of leukocyte
endothelial interaction and a reduction of proarteriogenic cytokine expression.
Consistently, miR-155-deficient macrophages exhibit a specific alteration of the
proarteriogenic cytokine expression profile, which is partly mediated by the
direct miR-155 target gene SOCS-1. CONCLUSIONS: Our data demonstrate that miR-155
exerts an antiangiogenic but proarteriogenic function in the regulation of
neovascularization via the suppression of divergent cell-specific target genes
and that its expression in both endothelial and bone marrow-derived cells is
essential for arteriogenesis in response to hindlimb ischemia in mice.
PMID- 25850726
TI - Mitochondrial ATP-sensitive potassium channel opening inhibits isoproterenol
induced cardiac hypertrophy by preventing oxidative damage.
AB - Cardiac hypertrophy is a chronic complex disease that occurs in response to
hemodynamic load and is accompanied by oxidative stress and mitochondrial
dysfunction. Mitochondrial ATP-sensitive K channels (mitoKATPs) have previously
been shown to prevent oxidative cardiac damage under conditions of
ischemia/reperfusion. However, the effect of these channels on cardiac
hypertrophy has not been tested to date. In this study, we show that treatment of
Swiss mice with isoproterenol (30 mg.kg.d) induces cardiac hypertrophy while
significantly decreasing the levels of reduced protein thiols, glutathione,
catalase, and superoxide dismutase activity, indicative of a condition of
oxidative imbalance. Treatment with diazoxide (a mitoKATP opener, 5 mg.kg.d)
normalized the levels of protein thiols and reduced glutathione, rescued
superoxide dismutase activity, and significantly prevented cardiac hypertrophy.
The protective effects of diazoxide were mitigated by the mitoKATP blockers 5
hydroxydecanoate (5 mg.kg.d) and glibenclamide (3 mg.kg.d), demonstrating that
they were related to activation of the channel. Taken together, our results
establish that mitoKATP activation promotes very robust prevention of cardiac
hypertrophy and associated oxidative imbalance and suggest that these channels
can be important drug targets for the pharmacological control of cardiac
hypertrophy.
PMID- 25850727
TI - Anagrelide treatment and cardiovascular monitoring in essential thrombocythemia.
A prospective observational study.
AB - In this prospective observational single-center study, 55 patients with essential
thrombocythemia who were candidates for second line treatment with anagrelide
(ANA) received a preliminary cardiovascular (CV) clinical, instrumental and
biochemical evaluation (CV history and symptoms, CV risk factors, blood pressure,
heart rate, ECG and ECHO-cardio parameters, Troponin I, NT-proBNP). After this in
depth CV screening, 54 out of 55 patients were deemed to be fit for ANA
treatment. Thirty-eight of the 55 patients received ANA treatment for a median of
36 months (range 3-48), and were monitored using the same CV evaluation. Fourteen
of these 38 patients manifested CV adverse events (10 palpitation, 4 edema, 2
arterial hypertension, 2 acute myocardial infarction) that were not predicted by
the in-depth CV evaluation, and that led to ANA withdrawal in only one case (non
cardiac refractory edema). In conclusion, the planned in-depth CV evaluation did
not appear to be necessary in ET patients to evaluate their suitability for ANA
treatment, and, moreover, was not able to predict the occurrence of CV adverse
events during ANA treatment. Nevertheless, the CV adverse events (mostly
palpitations and edema) were easily managed by the hematologists, and required
the cardiologist involvement in very few selected cases.
PMID- 25850728
TI - Question prompt list responds to information needs of myelodysplastic syndromes
patients and caregivers.
AB - Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic malignancies,
often poorly understood by patients. Our aim was to obtain the views of MDS
patients and family caregivers about a targeted question prompt list's (QPL)
potential utility, and to evaluate their information needs. This targeted QPL,
which included 53 suggested questions patients may ask onco-haematologists, was
developed. A self-administered questionnaire eliciting feedback about the QPL and
assessing its perceived usefulness was mailed to all members of Australian and
French patients' national MDS associations. Respectively, 301 MDS patients and 53
caregivers responded. Most (76.4%) were satisfied with the information provided
at MDS disclosure but would have liked more information about prognosis (69.3%).
Consistently, the three most useful questions focused on the risk of leukaemic
transformation, the impact of treatment on chances of survival and the severity
of the MDS. The majority (62.9%) of both patients and caregivers perceived the
QPL as 'absolutely' useful, particularly those who would have preferred more
information about prognosis (adjusted odds ratio=2.3, 95% confidence interval
[1.2-4.2], p=0.008). Our proposal of intervention through a QPL was generally
welcomed and could particularly address specific MDS patient needs regarding
prognosis information.
PMID- 25850729
TI - LFA-1-targeting Leukotoxin (LtxA; Leukothera(r)) causes lymphoma tumor regression
in a humanized mouse model and requires caspase-8 and Fas to kill malignant
lymphocytes.
AB - Leukotoxin (LtxA) is a protein secreted from the oral bacterium Aggregatibacter
actinomycetemcomitans. LtxA binds to the beta2 integrin lymphocyte-associated
function antigen-1 (LFA-1) on human white blood cells (WBCs), resulting in cell
death. LtxA is currently under investigation as a novel therapy (Leukothera((r)))
for treating hematologic malignancies and autoimmune diseases. We show here that
LtxA has potent in vivo anti-lymphoma activity in mice. LtxA caused complete
regression of B-cell tumors and promoted long-term survival of mice. The
mechanism of LtxA-mediated killing of malignant lymphocytes was further examined.
We found that LtxA kills malignant lymphocytes by a novel mechanism requiring the
death receptor Fas and caspase-8, but not Fas ligand (FasL) or caspase-9. We also
determined that LFA-1 and Fas are closely associated on the cell surface and this
proximity of LFA-1 and Fas could explain how signaling through an integrin can
lead to cell death. In addition to LFA-1, this work reveals a second surface
protein, Fas, that is critical for LtxA-mediated cell death. Knowledge of the
mechanism of cell death induced by LtxA will facilitate the development and
understanding of this potent experimental therapeutic agent.
PMID- 25850731
TI - Treatment targets in emergency departments: nurses' views of how they affect
clinical practice.
AB - AIMS AND OBJECTIVES: To understand nurses' views and experiences of four-hour
treatment targets in the emergency department and how this impacts clinical
decision-making throughout acute secondary care hospitals. BACKGROUND: In many
countries, national treatment targets in the emergency department have been
introduced. However, research and a recent enquiry into poor clinical care in one
hospital in the UK have highlighted that patient care may be compromised by the
need to meet these targets. DESIGN: Qualitative descriptive study as part of a
case study approach. METHODS: Semi-structured interviews were conducted with 31
nurses working in UK secondary care hospitals which had an emergency department.
Nurses were purposively sampled from three specialties: emergency arenas
(emergency department, n = 5; medical assessment n = 4 surgical receiving n = 2)
(n = 11), surgical wards (n = 11) and medical wards (n = 9). RESULTS: Nurses in
emergency arenas reported considerable burden, in terms of a very high workload
and pressure from senior staff to meet the target. Respondents reported that
negative impact on patient care for the majority of patients, excluding the most
sick, for whom emergency arena nurses reported that they ensured received
appropriate treatment, regardless of breaching treatment targets. Around half of
the nurses working outside emergency arenas felt pressure and amended their work
practices to enable colleagues in emergency arenas to meet treatment targets.
CONCLUSIONS: Four-hour targets were not viewed as clinically helpful by the
majority of nurses, some of whom questioned their appropriateness for patient
care. RELEVANCE TO CLINICAL PRACTICE: Policy makers and senior managers should
consider the suitability of treatment targets in the emergency department,
particularly in relation to working conditions for nurses and other health
professionals and its potential for negative impacts on patient care. While
targets remain in place, senior nurses and managers should support nurses who
breach the target to provide optimum clinical care.
PMID- 25850730
TI - Computational neuroimaging and population receptive fields.
AB - Functional magnetic resonance imaging (fMRI) noninvasively measures human brain
activity at millimeter resolution. Scientists use different approaches to take
advantage of the remarkable opportunities presented by fMRI. Here, we describe
progress using the computational neuroimaging approach in human visual cortex,
which aims to build models that predict the neural responses from the stimulus
and task. We focus on a particularly active area of research, the use of
population receptive field (pRF) models to characterize human visual cortex
responses to a range of stimuli, in a variety of tasks and different subject
populations.
PMID- 25850733
TI - Bilateral Cortical Encephalomalacia in a Patient Implanted With Bilateral Deep
Brain Stimulation for Alzheimer's Disease: A Case Report.
PMID- 25850732
TI - Onset of Mild Cognitive Impairment in Parkinson Disease.
AB - OBJECTIVE: Characterize the onset and timing of cognitive decline in Parkinson
disease (PD) from the first recognizable stage of cognitively symptomatic PD-mild
cognitive impairment (PD-MCI) to PD dementia (PDD). Thirty-nine participants
progressed from PD to PDD and 25 remained cognitively normal. METHODS: Bayesian
estimated disease-state models described the onset of an individual's cognitive
decline across 12 subtests with a change point. RESULTS: Subtests measuring
working memory, visuospatial processing ability, and crystalized memory changed
significantly 3 to 5 years before their first nonzero Clinical Dementia Rating
and progressively worsened from PD to PD-MCI to PDD. Crystalized memory deficits
were the hallmark feature of imminent conversion of cognitive status. Episodic
memory tasks were not sensitive to onset of PD-MCI. For cognitively intact PD,
all 12 subtests showed modest linear decline without evidence of a change point.
CONCLUSIONS: Longitudinal disease-state models support a prodromal dementia stage
(PD-MCI) marked by early declines in working memory and visuospatial processing
beginning 5 years before clinical diagnosis of PDD. Cognitive declines in PD
affect motor ability (bradykinesia), working memory, and processing speed
(bradyphrenia) resulting in PD-MCI where visuospatial imagery and memory
retrieval deficits manifest before eventual development of overt dementia. Tests
of episodic memory may not be sufficient to detect and quantify cognitive decline
in PD.
PMID- 25850734
TI - Introduction to a special issue on Skin disease, immune response and cytokines.
PMID- 25850736
TI - (E)-Specific direct Julia-olefination of aryl alcohols without extra reducing
agents promoted by bases.
AB - An unprecedented base-promoted direct olefination of aryl alcohols with sulfones
via a Julia-type reaction has been described. No extra reductants are needed for
Julia reaction since alcohols work as double sources of aldehydes and the
hydride. Generally high yields were given for both terminal and highly (E)
selective internal olefins.
PMID- 25850735
TI - Anatomical considerations for implant placements in first maxillary molar
extracted sites in East Asian patients.
AB - PURPOSE: With the advent of cone-beam computed tomography (CBCT) for
maxillofacial imaging, there has been a paradigm shift from two dimensional
panoramic radiography to three dimensional imaging. This study investigated the
microanatomy of the maxillary permanent first molar socket and its relationship
to the floor of the maxillary sinus, especially for immediate or early implant
placement. MATERIALS AND RESULTS: Sixty CBCT scans of 30 Malay and 30 Chinese
subjects were selected from over 300 archived images. Ninety-five percent of the
subjects had sinus floor extending anterior to the first molar, while 72% had the
floor dipping between the roots. Seventy-five percent of the patients had inter
radicular bone and almost 50% had intrusion of root apices into the floor of the
maxillary sinus. The dimensions of the socket were as follows: the mean width was
11.42 +/- 0.86 mm; the mean length was 7.70 +/- 0.56 mm; the mean height on the
coronal plane was 6.48 +/- 3.77 mm while on the sagittal plane it was 6.85 +/-
3.67 mm. CONCLUSIONS: Any implant length greater than the mean height of the
socket (approximately 7 mm) has a fair chance of perforation into the maxillary
sinus if placed without any additional adjunct procedures. In addition, 50% of
the apices opened into the maxillary sinus, thereby risking the creation of
perforations or root displacements into the maxillary sinus during exodontia
mandating CBCT scanning prior to any surgical implant procedures.
PMID- 25850738
TI - On the occurrence of a widespread contamination by herbicides of coral reef biota
in French Polynesia.
AB - Research has been conducted within the framework of the French Initiative for
Coral Reefs (IFRECOR) to assess pesticide pollution levels in the coral reef
trophic webs in French Polynesia. Unexpected widespread contamination by
herbicides was found in algae, fishes and macro-invertebrates located at various
levels of the reef trophic web. Concentrations in organisms investigated were for
the majority below the lowest observable effect level and do not pose a dietary
risk to native population who subsist on these fish. However, the widespread
contamination may affect the reef ecosystem in the future as coral symbiotic
algae, Symbidinium sp. (Dinophyta) are particularly sensitive to photosystem II
herbicides, particularly the substituted urea and triazine derivatives.
PMID- 25850739
TI - Citric acid enhances the phytoextraction of chromium, plant growth, and
photosynthesis by alleviating the oxidative damages in Brassica napus L.
AB - Chromium (Cr) toxicity is widespread in crops grown on Cr-contaminated soils and
has become a serious environmental issue which requires affordable strategies for
the remediation of such soils. This study was performed to assess the performance
of citric acid (CA) through growing Brassica napus in the phytoextraction of Cr
from contaminated soil. Different Cr (0, 100, and 500 MUM) and citric acid (0,
2.5, and 5.0 mM) treatments were applied alone and in combinations to 4-week-old
seedlings of B. napus plants in soil under wire house condition. Plants were
harvested after 12 weeks of sowing, and the data was recorded regarding growth
characteristics, biomass, photosynthetic pigments, malondialdehyde (MDA),
electrolytic leakage (EL), antioxidant enzymes, and Cr uptake and accumulation.
The results showed that the plant growth, biomass, chlorophyll contents, and
carotenoid as well as soluble protein concentrations significantly decreased
under Cr stress alone while these adverse effects were alleviated by application
of CA. Cr concentration in roots, stem, and leaves of CA-supplied plant was
significantly reduced while total uptake of Cr increased in all plant parts with
CA application. Furthermore, in comparison with Cr treatments alone, CA supply
reduced the MDA and EL values in both shoots and roots. Moreover, the activity of
superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT), and
ascorbate peroxidase (APX) in shoots and roots markedly increased by 100 MUM Cr
exposure, while decreased at 500 MUM Cr stress. CA application enhanced the
activities of antioxidant enzymes compared to the same Cr treatment alone. Thus,
the data indicate that exogenous CA application can increase Cr uptake and can
minimize Cr stress in plants and may be beneficial in accelerating the
phytoextraction of Cr through hyper-accumulating plants such as B. napus.
PMID- 25850737
TI - In situ remediation technologies for mercury-contaminated soil.
AB - Mercury from anthropogenic activities is a pollutant that poses significant risks
to humans and the environment. In soils, mercury remediation can be technically
challenging and costly, depending on the subsurface mercury distribution, the
types of mercury species, and the regulatory requirements. This paper introduces
the chemistry of mercury and its implications for in situ mercury remediation,
which is followed by a detailed discussion of several in situ Hg remediation
technologies in terms of applicability, cost, advantages, and disadvantages. The
effect of Hg speciation on remediation performance, as well as Hg transformation
during different remediation processes, was detailed. Thermal desorption,
electrokinetic, and soil flushing/washing treatments are removal technologies
that mobilize and capture insoluble Hg species, while containment,
solidification/stabilization, and vitrification immobilize Hg by converting it to
less soluble forms. Two emerging technologies, phytoremediation and
nanotechnology, are also discussed in this review.
PMID- 25850740
TI - Direct emissions of N2O, CO 2, and CH 4 from A/A/O bioreactor systems: impact of
influent C/N ratio.
AB - Direct emissions of N2O, CO2, and CH4, three important greenhouse gases (GHGs),
from biological sewage treatment process have attracted increasing attention
worldwide, due to the increasing concern about climate change. Despite the
tremendous efforts devoted to understanding GHG emission from biological sewage
treatment process, the impact of influent C/N ratios, in terms of chemical oxygen
demand (COD)/total nitrogen (TN), on an anaerobic/anoxic/oxic (A/A/O) bioreactor
system has not been investigated. In this work, the direct GHG emission from
A/A/O bioreactor systems fed with actual sewage was analyzed under different
influent C/N ratios over a 6-month period. The results showed that the variation
in influent carbon (160 to 500 mg/L) and nitrogen load (35 to 95 mg/L)
dramatically influenced pollutant removal efficiency and GHG production from this
process. In the A/A/O bioreactor systems, the GHG production increased from 26-39
to 112-173 g CO2-equivalent as influent C/N ratios decreased from 10.3/10.7 to
3.5/3.8. Taking consideration of pollutant removal efficiency and direct biogenic
GHG (N2O, CO2, and CH4) production, the optimum influent C/N ratio was determined
to be 7.1/7.5, at which a relatively high pollutant removal efficiency and
meanwhile a low level of GHG production (30.4 g CO2-equivalent) can be achieved.
Besides, mechanical aeration turned out to be the most significant factor
influencing GHG emission from the A/A/O bioreactor systems.
PMID- 25850741
TI - Relationships among bulk soil physicochemical, biochemical, and microbiological
parameters in an organic alfalfa-rice rotation system.
AB - The microbial communities of bulk soil of rice paddy fields under an ancient
organic agriculture regimen, consisting on an alfalfa-rice rotation system, were
characterized. The drained soil of two adjacent paddies at different stages of
the rotation was compared before rice seeding and after harvesting. The
relationships among the soil microbial, physicochemical, and biochemical
parameters were investigated using multivariate analyses. In the first year of
rice cropping, aerobic cultivable heterotrophic populations correlated with
lineages of presumably aerobic bacteria (e.g., Sphingobacteriales,
Sphingomonadales). In the second year of rice cropping, the total C content
correlated with presumable anaerobic bacteria (e.g., Anaerolineae). Independently
of the year of rice cropping, before rice seeding, proteolytic activity
correlated positively with the cultivable aerobic heterotrophic and ammonifier
populations, the soil catabolic profile and with presumable aerobes (e.g.,
Sphingobacteriales, Rhizobiales) and anaerobes (e.g., Bacteroidales,
Anaerolineae). After harvesting, strongest correlations were observed between
cultivable diazotrophic populations and bacterial groups described as comprising
N2 fixing members (e.g., Chloroflexi-Ellin6529, Betaproteobacteria,
Alphaproteobacteria). It was demonstrated that chemical parameters and microbial
functions were correlated with variations on the total bacterial community
composition and structure occurring during rice cropping. A better understanding
of these correlations and of their implications on soil productivity may be valid
contributors for sustainable agriculture practices, based on ancient processes.
PMID- 25850742
TI - Highly stable rice-straw-derived charcoal in 3700-year-old ancient paddy soil:
evidence for an effective pathway toward carbon sequestration.
AB - Recalcitrant charcoal application is predicted to decelerate global warming
through creating a long-term carbon sink in soil. Although many studies have
showed high stability of charcoal derived from woody materials, few have focused
on the dynamics of straw-derived charcoal in natural environment on a long
timescale to evaluate its potential for agricultural carbon sequestration. Here,
we examined straw-derived charcoal in an ancient paddy soil dated from ~3700
calendar year before present (cal. year BP). Analytical results showed that soil
organic matter consisted of more than 25% of charcoal in charcoal-rich layer.
Similarities in morphology and molecular structure between the ancient and the
fresh rice-straw-derived charcoal indicated that ancient charcoal was derived
from rice straw. The lower carbon content, higher oxygen content, and obvious
carbonyl of the ancient charcoal compared with fresh rice straw charcoal implied
that oxidation occurred in the scale of thousands years. However, the dominant
aromatic C of ancient charcoal indicated that rice-straw-derived charcoal was
highly stable in the buried paddy soil due to its intrinsic chemical structures
and the physical protection of ancient paddy wetland. Therefore, it may suggest
that straw charcoal application is a potential pathway for C sequestration
considering its longevity.
PMID- 25850743
TI - Energy efficiency through integrated environmental management.
AB - Integrated environmental management became an economic necessity after industrial
development proved to be unsustainable without consideration of environmental
direct and indirect impacts. Energy dependency and air pollution along with
climate change grew into major challenges facing developed and developing
countries alike. Thus, a new global market structure emerged and changed the way
we do trade. The search intensified for alternatives to petroleum. However,
scientists, policy makers, and environmental activists agreed to focus on
strategic conservation and optimization of energy use. Environmental concerns
will remain partially unaddressed with the current pace of consumption because
greenhouse gas emissions will continue to rise with economic growth. This paper
discusses energy efficiency, steady integration of alternative sources, and
increased use of best available technologies. Energy criteria developed for
environmental labeling certification are presented. Our intention is to encourage
manufacturers and service providers to supply consumers with less polluting and
energy-consuming goods and services, inform consumers of the environmental and
energy impacts, and thereby instill sustainable and responsible consumption. As
several programs were initiated in developed countries, environmental labeling
requirements created barriers to many exports manufactured in developing
countries, affecting current world trade and putting more pressure on countries
to meet those requirements. Defining an institutional and legal framework of
environmental labeling is a key challenge in implementing such programs for
critical economic sectors like tourism, textiles, and food production where
energy needs are the most important aspect to control. A case study of Tunisia
and its experience with eco-labeling is presented.
PMID- 25850744
TI - Isolation and molecular characterization of multidrug-resistant halophilic
bacteria from shrimp farm effluents of Parangipettai coastal waters.
AB - Multidrug resistance of heterotrophic bacteria isolated from an aquaculture farm
effluent in Parangipettai, at the southeastern coast of India, was investigated.
In the initial screening, 27 antibiotic-resistant strains were isolated. All the
strains were tested for antibiotic susceptibility against chloramphenicol with
varying concentrations. From these, two highly resistant strains, i.e. S1 and S5,
were isolated. The selected strains were identified by 16S ribosomal RNA (rRNA)
sequencing techniques and confirmed as Bacillus pumilus and Bacillus flexus. Both
the antibiotic-resistant strains were further utilized for multidrug
susceptibility test by using various antibiotics. These two strains showed
antibiotic resistance to 14 of 17 antibiotics tested. Both microdilution assay
and well assay methods were used to determine the minimal inhibitory
concentration (MIC) for the sensitive strains. Both the tests were shown to be
almost similar. Our study highlights the occurrence of multidrug-resistant
bacteria in the shrimp farm effluents.
PMID- 25850745
TI - Biodecolorization of recalcitrant dye as the sole sourceof nutrition using
Curvularia clavata NZ2 and decolorization ability of its crude enzymes.
AB - Extensive use of recalcitrant azo dyes in textile and paper industries poses a
direct threat to the environment due to the carcinogenicity of their degradation
products. The aim of this study was to investigate the efficiency of Curvularia
clavata NZ2 in decolorization of azo dyes. The ability of the fungus to
decolorize azo dyes can be evaluated as an important outcome as existing effluent
treatment is unable to remove the dyes effectively. C. clavata has the ability to
decolorize Reactive Black 5 (RB5), Acid Orange 7 (AO7), and Congo Red azo dyes,
utilizing these as sole sources of carbon and nitrogen. Ultraviolet-visible (UV
vis) spectroscopy and Fourier infrared spectroscopy (FTIR) analysis of the
extracted RB5's metabolites along with desorption tests confirmed that the
decolorization process occurred due to degradation and not merely by adsorption.
Enzyme activities of extracellular enzymes such as carboxymethylcellulase
(CMCase), xylanase, laccase, and manganese peroxidase (MnP) were also detected
during the decolorization process. Toxicity expressed as inhibition of
germination was reduced significantly in fungal-treated azo dye solution when
compared with the control. The cultivation of C. clavata under sequential batch
system also recorded a decolorization efficiency of above 90%. The crude enzyme
secreted by C. clavata also showed excellent ability to decolorize RB5 solutions
with concentrations of 100 ppm (88-92%) and 1000 ppm (70-77%) without redox
mediator. This proved that extracellular enzymes produced by C. clavata played a
major role in decolorization of RB5.
PMID- 25850746
TI - Phytoremediation potential of Miscanthus * giganteus and Spartina pectinata in
soil contaminated with heavy metals.
AB - The aim of this work was to assess the suitability of Miscanthus * giganteus and
Spartina pectinata link to Cu, Ni, and Zn phytoremediation. A 2-year microplot
experiment with the tested grasses growing on metal-contaminated soil was carried
out. Microplots with cement borders, measuring 1 * 1 * 1m, were filled with
Haplic Luvisols soil. Simulated soil contamination with Cu, Ni, and Zn was
introduced in the following doses in mg kg(-1): 0-no metals, Cu1-100, Cu2-200,
Cu3-400, Ni1-60, Ni2-100, Ni3-240, Zn1-300, Zn2-600, and Zn3-1200. The
phytoremediation potential of grasses was evaluated using a tolerance index (TI),
bioaccumulation factor (BF), bioconcentration factor (BCF), and translocation
factor (TF). S. pectinata showed a higher tolerance to soil contamination with
Cu, Ni, and Zn compared to M. * giganteus. S. pectinata was found to have a high
suitability for phytostabilization of Zn and lower suitability of Cu and Ni. M. *
giganteus had a lower phytostabilization potential than S. pectinata. The
suitability of both grasses for Zn phytoextraction depended on the age of the
plants. Both grasses were not suitable for Cu and Ni phytoextraction. The
research showed that one-season studies were not valuable for fully assessing the
phytoremediation potential of perennial plants.
PMID- 25850748
TI - Utilization of heavy metal-rich tannery sludge for sweet basil (Ocimum basilicum
L.) cultivation.
AB - Unlike food crops, essential oil-bearing crops in which the oil is extracted
through hydro-distillation can be a suitable crop to be grown in heavy metal
polluted soils as the oil does not carry any heavy metal. In a field experiment
conducted at CIMAP, Lucknow, India during 2011 and 2012, influence of six doses
of tannery sludge viz 0, 10, 20, 30, 40, and 50 t ha(-1) were tested, taking
sweet basil (Ocimum basilicum) as the test crop. Maximum herb yield was obtained
with the application of sludge at 20 t ha(-1). While in root, accumulation of Cd
and Pb increased significantly up to 20 t ha(-1), Cr accumulation increased with
increasing the dose of tannery sludge reaching maximum at 50 t ha(-1). Essential
oil yield of basil (Ocimum basilicum) was significantly affected due to sludge
application. Quality of essential oil, in term of chemical constituents, however,
was marginally influenced due to tannery sludge application.
PMID- 25850747
TI - Spatial distribution and temporal trends of mercury and arsenic in remote
timberline coniferous forests, eastern of the Tibet Plateau, China.
AB - An intensive investigation was conducted to study the spatial distribution and
temporal variety trend of mercury and arsenic in plant tissue and soil profile in
the eastern of the Tibet Plateau and to explore the possible sources of these two
elements. At present, rare information is available on mercury (Hg) and arsenic
(As) of timberline forests in the Tibet Plateau. Here, we present preliminary
results on these two elements in leaves, twigs, root, litterfall, and soil.
Geostatistical analyst of the ArcGIS 10.0 was used to determine the trait of
spatial distribution of these two elements. Total arsenic (TAs) mean
concentrations in the leaves, twigs, root, litterfall, and A- and C-layer soil
ranged from 0.12 mg kg(-1) (n = 60), 0.35 mg kg(-1) (n = 60), 0.48 mg kg(-1) (n =
42), 1.52 mg kg(-1) (n = 84), 16.51 mg kg(-1) (n = 69), and 26.72 mg kg(-1) (n =
69), respectively. Total Hg (THg) mean concentrations in leaves, twigs, root,
litterfall, and A- and C-layer soil were 0.0121 mg kg(-1) (n = 60), 0.0078 mg kg(
1) (n = 60), 0.0171 mg kg(-1) (n = 42), 0.0479 mg kg(-1) (n = 84), 0.0852 mg kg(
1) (n = 75), and 0.0251 mg kg(-1) (n = 75), respectively. In general, litterfall
trended to accumulate high concentrations of Hg and As. Mercury in the timberline
forest showed an increasing trend, whereas arsenic concentrations showed a
decreasing trend in A-layer soil and an increasing trend in C-layer soil due to
the easy mobile ability of As. Southwest and southeast monsoon could be the
influencing factors, and Hg emission from India and China was the possible source
of this study area through using a HYSPLIT (Hybrid Single-Particle Lagrangian
Integrated Trajectory) model. It is believed that these observations may offer
scientists and policymakers additional understanding of Hg and As concentrations
in the remote timberline area, eastern of the Tibet Plateau.
PMID- 25850749
TI - Combination therapy in hypertension: what are the best options according to
clinical pharmacology principles and controlled clinical trial evidence?
AB - Despite extensive debate about the first choice for treating essential
hypertension, monotherapy effectively normalizes blood pressure (BP) values in
only a limited number of hypertensive patients. Thus, the aim of combination
therapy should always be to both improve BP control and to reduce cardiovascular
events. Antihypertensive drugs can be effectively combined if they have different
and complementary mechanisms of action. This is crucial to obtain additive BP
lowering effects without impacting on tolerability. One typical combination is
the association of drugs blocking and stimulating the renin-angiotensin system
(RAS) (angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor
blocker and calcium antagonist or diuretic, respectively). In contrast, some
combinations (e.g., calcium antagonists plus diuretics or beta-blockers plus RAS
blockers) have no additive BP-lowering effects, while other combinations (e.g.,
clonidine plus alpha-1 receptor blockers) can have a negative interaction.
Regardless, BP reduction is not the only mechanism that reduces cardiovascular
risk. Scientific evidence indicates that some drug classes are better than others
in this respect, and therefore some drug combinations are also better than
others. The results of the ASCOT-BPLA and ACCOMPLISH trials suggested that an ACE
inhibitor/calcium antagonist combination had better cardioprotective effects than
beta-blocker/diuretic or ACE inhibitor/diuretic combinations. It is worth noting
that no controlled clinical trials have used hard endpoints when investigating
the effects of an angiotensin receptor blocker/calcium antagonist combination. In
conclusion, combination therapy is needed for optimal antihypertensive
management, with the first choice being an ACE inhibitor plus a calcium
antagonist. This approach should improve BP control and provide better
cardiovascular protection.
PMID- 25850751
TI - Gross hematuria caused by the nutcracker syndrome.
PMID- 25850750
TI - Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor
Agonist Selexipag.
AB - PURPOSE: Targeting the prostacyclin pathway is an effective treatment option for
pulmonary arterial hypertension (PAH). Patients with PAH have a deficiency of
prostacyclin and prostacyclin synthase. Selexipag is an orally available and
selective prostacyclin receptor (IP receptor) agonist. Selexipag is hydrolyzed to
its active metabolite ACT-333679, also a selective and potent agonist at the IP
receptor. METHODS: In this phase I study the pharmacokinetics (PK) and
tolerability of single and multiple ascending doses of selexipag were
investigated in a double-blind, placebo-controlled manner in 64 healthy male
subjects. An additional group of 12 subjects received an open-label dose of
selexipag 400 MUg in the fasted condition and after a meal. RESULTS: Maximum
plasma concentrations of selexipag and ACT-333679 were reached within 2.5 and 4
h, respectively, with mean half-lives of 0.7-2.3 and 9.4-14.22 h. In the presence
of food, exposure to ACT-333679 was decreased by 27 %. The most frequent adverse
event was headache. Selexipag was well tolerated up to a single dose of 400 MUg
and multiple doses of 600 MUg following an up-titration step. No relevant
treatment-related effects on vital signs, clinical laboratory, and
electrocardiogram (ECG) parameters were detected. CONCLUSION: Selexipag exhibits
a good tolerability profile and PK properties that warrant further investigation.
PMID- 25850753
TI - Supra-therapeutic tacrolimus concentrations associated with concomitant
nicardipine in pediatric liver transplant recipients.
AB - Tacrolimus is prescribed to prevent allograft rejection in pediatric liver
transplant recipients; however, its metabolism through the cytochrome P-450
enzyme system presents a multitude of challenges in regard to drug interactions.
Here, we describe four children (ages 1.4-8.7 yr) who acutely developed supra
therapeutic serum tacrolimus trough concentrations, despite standard dosing,
while on concomitant nicardipine therapy following liver transplantation. Even
though tacrolimus regimens were altered (dosage reductions and held doses), serum
tacrolimus concentrations remained elevated. Resolution of high tacrolimus
concentrations was achieved only after the discontinuation of nicardipine.
Following the termination of nicardipine, all children eventually required dosage
increases in their tacrolimus regimens to re-achieve target serum concentrations.
We conclude that concomitant use of tacrolimus and nicardipine can result in high
tacrolimus concentrations due to the inhibition of cytochrome p450 enzymes
responsible for the metabolism of tacrolimus. We encourage clinicians to consider
alternative antihypertensive options in children on tacrolimus therapy. If
nicardipine therapy is necessary, we recommend a 50% reduction in tacrolimus dose
and daily serum concentration monitoring.
PMID- 25850752
TI - Competition between toxic and non-toxic Microcystis aeruginosa and its ecological
implication.
AB - The frequency of toxic cyanobacterial blooms has increased in recent decades, but
the factors that regulate the dominance of toxin-producing cyanobacteria over non
toxin-producing strains of one species are still obscure. This study examined the
effects of temperature, light intensity, nitrate and phosphate on the dominance
of MC-producing and non-MC-producing strains of Microcystis aeruginosa in
monoculture and co-culture experiments. In the monoculture experiments, growth
rates of the non-MC-producing strain were higher than those of the MC-producing
strain under the same growth conditions. However, at the end of the co-culture
experiments, the MC-producing strain became surprisingly dominant in all
treatments except when treated with extreme low phosphate concentrations. Higher
temperatures and nutrient levels can shift the dominance more quickly towards the
toxic strain. The dominance may be explained by allelopathic interactions through
allelochemicals and other secondary metabolites, but not MC. Environmental
factors such as extremely low phosphate content may exert an indirect effect on
strain dominance by changing the production of allelochemicals. Our findings
highlight the complications in predicting competitive outcome for cyanobacterial
strains in natural environments.
PMID- 25850755
TI - Health literacy training for health professions students.
AB - OBJECTIVE: This pilot project assessed the effectiveness of training health
professionals in (1) readability assessment of written health materials, (2)
plain language editing, and (3) formatting materials so they are easy to
understand and use. METHODS: Over six semesters, five students participated in
the project. Students were trained to assess document readability, confirm and
interpret readability results and "stamp" the documents with results. Students
then edited documents under supervision, via revised documents were re-assessed
for readability and approved. Training was assessed through readability score
comparison and exit interviews with students. RESULTS: Most original readability
scores were 10th grade to college level. After editing, the average reading level
of 73% was 6th grade or better. Students and supervisor rated skill levels as
"proficient" at the end of the semester. CONCLUSION: To address the gap between
document reading level and patients' reading ability, health documents should be
assessed and edited for plain language. Working with patient documents from
various health fields, our program effectively trained health professions
students in these skills. PRACTICE IMPLICATIONS: Training health professions
students in readability assessment and plain language editing can reduce literacy
demands on patients and address the need for professionals with these skills.
PMID- 25850754
TI - Immunostaining of ?Np63 (using the p40 antibody) is equal to that of p63 and
CK5/6 in high-grade ductal carcinoma in situ of the breast.
AB - As a result of breast cancer screening programs, high-grade ductal carcinoma in
situ (DCIS) of the breast is diagnosed more often. Frequently, a DCIS diagnosis
can only be made using immunohistochemical stains to visualize the myoepithelial
layer in order to assess microinvasion. Standard markers for myoepithelial cells
are CK5/6 and p63. An isoform of the latter, ?Np63, is recognized by a recently
developed antibody, p40. Here, we compare the standard myoepithelial markers
CK5/6 and p63 with p40. We immunostained full sections of tissue samples of 35
high-grade DCIS and compared the staining pattern of CK5/6, p63 and p40 in tumour
tissue and in normal glands. Staining patterns of myoepithelial cells for p63 and
p40 were similar in terms of the percentage of stained nuclei. In all cases, p63
was strongly expressed, while this was the case for p40 in 31 (89%) and
moderately in 4 (11%) cases. All but one case (97%) showed a similar percentage
of stained myoepithelial cells in comparing CK5/6 and p40 staining. CK5/6
expression was heterogeneous and strong/moderate/weak in 60, 34 and 6 %
respectively. Compared to surrounding normal glands, staining of myoepithelial
cells for all three markers in the neoplastic lesion was attenuated. In high
grade DCIS, p40 staining is highly specific for myoepithelial cells. Its staining
pattern and intensity are equal to p63, which opens up its use for daily
practice. Staining with p40 is less heterogeneous than that for CK5/6.
PMID- 25850756
TI - Occupational therapists' shared decision-making behaviors with patients having
persistent pain in a work rehabilitation context: A cross-sectional study.
AB - OBJECTIVE: In a work rehabilitation context, we assessed occupational therapists'
(OTs) shared decision-making (SDM) behaviors with individuals having persistent
pain and explored factors influencing SDM behaviors. METHODS: A cross-sectional
study that used audio-recordings of work rehabilitation consultations between OTs
trained in SDM and a convenient sample of patients. Eligible patients were: off
work for >=12 weeks due to persistent pain associated with a musculoskeletal
disorder, starting a work rehabilitation program, and French speaking.
Transcripts were analyzed using the Observing Patient Involvement in Shared
Decision Making (OPTION) instrument and assessed patients' decisional conflict
and socioeconomic status. RESULTS: Of 15 OTs trained in SDM, 11 (90% female),
provided audiotaped SDM meetings with 37 patients (40.5% female; aged 18-62
years). Their average OPTION score was 53.94 out of 100 (SD=9.68; range 35.42
70.83), indicating basic skills. Significant factors associated with OPTION
scores (R (2)adjusted=21.7%) were the interview length (p=0.008) and level of
patient education (p=0.038). CONCLUSION: Basic SDM behaviors were integrated in
the practice of OTs trained in SDM. PRACTICE IMPLICATIONS: Evaluating SDM
behaviors is a step toward providing OTs with performance feedback toward
achieving client-centered care.
PMID- 25850757
TI - The effectiveness of dopamine agonists for treatment of neuropsychiatric symptoms
post brain injury and stroke.
AB - OBJECTIVE: Traumatic brain injury and stroke are among the leading causes of
neurological disability worldwide. Although dopaminergic agents have long been
associated with improvement of neuropsychiatric outcomes, to date much of the
evidence to date has been in case reports and case series or open label trials.
METHODS: We undertook a systematic review of double-blinded randomised controlled
trials (RCT) to determine the effect of dopaminergic agents on pre-defined
outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management
and (d) cognitive function. Databases searched were: Medline, EMBASE, and
PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP
Medical database were also searched. All identified studies, were further hand
searched. RESULTS: We identified six studies providing data on 227 participants,
150 of whom received dopaminergic therapy. Trials were compromised by cross-over
design, inadequate wash out period, small numbers and heterogeneous outcome
measures. However one good quality RCT demonstrates the efficacy of amantadine in
behavioural management. One further RCT shows methylphenidate-levodopa is
efficacious for mood post-stroke. One study shows rotigotine to improve hemi
inattention caused by prefrontal damage. CONCLUSION: Our systematic review
demonstrates an evolving evidence base to suggest some benefits in agitation and
aggression, mood and attentional deficits. However, there are key limitations of
the studies undertaken to date involving small numbers of participants,
heterogeneous outcome measures, and variable study designs. There is a need for
on-going large prospective double-blind RCTs in these medications using
standardised criteria and outcomes to fully understand their effectiveness in
this patient group.
PMID- 25850758
TI - Retraction Note to: Identification of gene expression profile in the rat brain
resulting from acute alcohol intoxication.
PMID- 25850759
TI - An appraisal on the occurrence of foot-and-mouth disease virus serotypes in
cattle and buffaloes, Pakistan.
AB - Foot-and-mouth disease (FMD) is a livestock disease that has serious economic
repercussions. Here, we report the laboratory results for samples from suspected
outbreaks that were sent for confirmation of FMD in Pakistan. From January 2010
to December 2011, 132 suspected outbreaks were investigated, and samples from 58
out of the 76 outbreaks sent to the National Veterinary Laboratory (NVL) were
positive. The highest proportion of positives were of serotype O (65.52 %),
followed by serotype A (24.14 %) and serotype Asia-1 (10.35 %), whereas amongst
the samples sent to the World Reference Laboratory, Pirbright, UK (WRL), samples
from 48 out of 56 outbreaks were confirmed to be FMD positive, with the following
serotypes identified: O (56.25 %), Asia-1 (37.50 %) and A (6.25 %). The outbreaks
affected cattle, buffalo and mixed (cattle and buffalo) herds at rates of 91, 70
and 76 %, respectively. The trend of positive outbreaks was higher in the months
of winter and late spring (November to April). Although the serotype O isolates
and some of the serotype A isolates from the field samples resembled the vaccine
strains (r-value >= 0.3), this was not the case for the Asia-1 isolates. These
results help to improve our understanding of the occurrence and distribution of
FMD in cattle and buffaloes in Pakistan and to provide baseline information for
the FMD progressive control program in the country.
PMID- 25850760
TI - Experimental infection of mice with bovine viral diarrhea virus.
AB - The objective of this study was to test the ability of bovine viral diarrhea
virus (BVDV) to infect mice. Two mice each were either mock infected or
inoculated with one of three BVDV strains by the intraperitoneal (IP) (n = 8) or
intranasal (IN) (n = 8) route. All mice were euthanized at day 7 postinfection
(p.i.). None of the infected mice exhibited any clinical signs of illness;
however, the tissues harvested after BVDV challenge showed significant
histopathological changes. Blood samples from five mice that were injected IP and
one mouse that was inoculated IN were positive for BVDV by reverse transcription
polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was used to assess
the presence of viral antigen in the organs of mice infected with three BVDV
strains. In IP-injected mice, BVDV antigen was detected in the spleen (5/6),
mesenteric lymph nodes (4/6), lymphatic tissue of the lung (3/6), lung (1/6), and
stomach (1/6) of the infected mice; however, it was not detected in the liver
(0/6) or kidney (0/6). In IN-inoculated mice, BVDV antigen was detected in the
lung and mesenteric lymph nodes of one BVDV-infected mouse but was not detected
in other tissues. The results of this study suggest that the spleen is the most
reliable tissue for BVDV antigen detection using IHC in the IP-injected group.
Our study demonstrates that mice can be infected by BVDV. This is the first
report of BVDV infection in mice.
PMID- 25850761
TI - Polymorphisms in the retinoic acid-1 like-receptor family of genes and their
association with clinical outcome of dengue virus infection.
AB - Polymorphisms in the DDX58 and IFIH1 genes, which code for the retinoic acid
inducible gene-1 protein and myeloid differentiation factor (MDA) 5, were
investigated in 120 dengue (DEN) cases (88 dengue fever [DF] cases and 32 dengue
hemorrhagic fever [DHF] cases) and 109 healthy controls (HCs) to investigate
their association with dengue. The results revealed a lower carrier frequency of
the DDX58 rs3205166 G allele in DEN than in HCs and a higher frequency of the
DDX58 rs669260 T/C genotype in DHF than in DF cases (P = 0.043, OR with 95 % CI
3.358 [1.038-10.861]). This suggests that polymorphisms in DDX58 gene influence
the clinical outcome of DENV infection.
PMID- 25850762
TI - [Respiratory emergencies and airway management in children].
AB - Respiratory emergencies in children are frequent and are caused by the specific
airway anatomy and the susceptibility for infections.This article reviews the
specific approach to pediatric airway management. According to the ABC guidelines
of the European Resuscitation Council, the described algorithm should help to
identify, classify, and treat such emergencies, giving those with less pediatric
experience a tool for the management of respiratory illness in children. Focus is
on the emergency care of the most common diseases in this age group.
PMID- 25850764
TI - Using Strictosidine Synthase to Prepare Novel Alkaloids.
AB - The Pictet-Spenglerasestrictosidine synthase (STR) has been characterized as the
central enzyme in the biosynthesis of around 2000 monoterpenoid indole alkaloids
in plants. In the light of a high therapeutic value and huge scaffold diversity
these alkaloids represent, STR as an enzyme has attracted great attentions in
recent years, intending to be utilized in the formation of new interesting
alkaloids with unusual substitution pattern or even with novel scaffolds. For
outlining the application potential that STR possesses, together with insight
into the reaction mechanism catalyzed by STR, strategies and methods for
exploring the applicability of STR have been updated in this article by taking R.
serpertina STR(RS-STR) and C. roseus.STR (CR-STR) as representative models,
followed by introducing the latest released complex structures of RS-STR with new
substrates. Examples provided here, including substrate scaffold tailoring, X-ray
crystal complex structure comparison, protein engineering and biosynthetic
pathway reprogramming, pave the way to finally construct novel alkaloids
libraries by chemo-enzymatic approaches.
PMID- 25850763
TI - [Aspiration and pneumonia risk after preclinical invasive resuscitation:
Endotracheal intubation and supraglottic airway management with the laryngeal
tube S].
AB - BACKGROUND: Laryngeal tubes (LT) have substantially facilitated emergency airway
management. However, it remains unclear whether LTs provide comparable protection
against aspiration or even higher rates of aspiration and pneumonia compared to
endotracheal intubation (ET) as the former gold standard. METHODS: The indices
for aspiration and early onset pneumonia in patients after preclinical airway
management by either LT or ET were retrospectively analyzed. Furthermore, in
hospital mortality was analyzed. RESULTS: A total of 90 patients with invasive
ventilation by either ET (n = 69) or LT (n = 21) were analyzed. Patients were
excluded if indication for ventilation was pneumonia, aspiration, drowning, or if
they had preexisting tracheotomy. The ET and LT groups did not differ regarding
age (ET: 62 +/- 16 years, LT: 64 +/- 8 years, p = 0.56), female gender (ET:
23.2%, LT: 33.3%, p = 0.25), or first paO2/FIO2 (ET: 300 +/- 164, LT: 342 +/-
178, p = 0.3). The majority of patients were survivors of out-of-hospital cardiac
arrest (OHCA, 72.2%), with a significantly higher OHCA rate in the LT group (LT:
95.2% ET: 65.2%, p = 0.006). Analysis for radiological or endoscopic evidence of
pulmonary aspiration revealed a higher aspiration rate in the ET group (43.5%,
LT: 23.8%, p = 0.08), especially after OHCA (ET: 48.9%, LT: 20%, p = 0.025). In
parallel, early onset pneumonia as a correlate for microaspiration in patients
without evident aspiration was observed more frequently in ET patients (41% vs.
25%, p = 0.21). In OHCA patients without aspiration, rates of pneumonia were
similar (ET: 26.1%, LT: 25%; p = 0.62). Analysis of in-hospital mortality showed
significantly higher mortality in the LT group (57.1% vs 30.4%, p = 0.026). Also
in OHCA patients, higher mortality was observed in the LT group (60 vs. 28.9%, p
= 0.018). DISCUSSION AND CONCLUSION: Airway management by LT was not associated
with higher risk of aspiration. In contrast, higher rates of aspiration and
pneumonia were observed after ET, especially in OHCA patients. However, a
possible prognostic impact of supraglottic airway devices remains to be
elucidated.
PMID- 25850765
TI - Sugars that Glow in the Dark: Fluorescent Tagged Glucose Bioprobes and their
Facilitation of the Drug Discovery Process
AB - Fluorescent tagged glucose probes offer an attractive alternative to traditional,
radioactive based methods for measuring glucose flux in biological systems. Thus,
it could be envisaged that these probes would be widely used. However, this is
not the case and, since their development in the mid-1980s, fluorescent tagged
glucose bioprobes are relatively underutilized in biological research compared to
radioactive methods, with only a small number (<10) publications per year using
these probes. However, within the past five years there has been a surge in
research activity. By the year 2012, numerous novel probes were developed and the
number of research publications dramatically increased. This was especially
relevant for drug discovery applications related to cancer, neurology and
diabetes research. In this review article, we discuss the research impact of
these bioprobes and assess which probes have been most successfully applied to
drug discovery applications. Significantly, we also discuss latest research that
shows the potential of these probes to be used for drug discovery in animal
models and their application to in vivo-based drug validation. Overall, we hope
that this review will raise awareness of the research opportunities that these
probes offer to the drug discovery research community.
PMID- 25850766
TI - Exploiting molecular virulence determinants in Burkholderia to develop vaccine
antigens.
AB - The Burkholderia genus is a highly diverse group of species that are distributed
throughout a wide range of environments and habitats. Among this group, which is
remarkable for its adaptability to a wider range of environmental conditions
including disinfectants and organic solvents, are a subgroup that represents some
of the most difficult to treat infections. This subgroup includes Burkholderia
pseudomallei, the causative agent of melioidosis; B. mallei, the causative agent
of glanders and B. cepacia complex (Bcc) which causes opportunistic infections in
people with cystic fibrosis and immunocompromised patients. The latter pathogen
is itself a group of 18 distinct, but, closely related species. The adaptability
of this group allows the expression of a rich selection of molecular virulence
determinants to facilitate its survival in the diverse habitats that it
colonises. This review will describe a selection of these associated with human
infection; comparing them across the three pathogens and highlighting their
potential roles as vaccine candidates. Better integration of the knowledge on the
pathogenesis and molecular determinants of virulence for these Burkholderia spp
may allow the development of more efficacious vaccines.
PMID- 25850767
TI - Molecular and cellular pathways as treatment targets for biologic therapies in
systemic sclerosis.
AB - Recent advances have shed light on the complex pathogenic processes that underlie
the development and progression of Systemic Sclerosis (SSc) but management of the
disease remains problematic and curative treatment is not available. Better
understanding of the underlying pathology has enabled novel therapeutic
approaches to be investigated, as therapies in rheumatology are becoming
increasingly disease/ organ-specific, targeting unique biological networks and
signalling pathways. The pathophysiologic and clinical pleiomorphism of SSc
however, represents a major barrier to conducting large well-controlled studies
for the evaluation of non-selective immunosuppressive and novel highly selective
agents. Therapeutic biologic strategies targeting inflammatory or profibrotic
cytokines and lymphocyte activation proved to be efficacious in other systemic
rheumatic diseases but have demonstrated contradictory results in SSc. Blocking
of tumour necrosis factor alpha and interleukin-6 may improve SSc-associated
arthritis, while depletion of B-cells may have benefits for skin and lung
fibrosis, but randomized studies are needed. In this review we critically
appraise available data for the treatment of SSc focusing on immunologic and
antifibrotic strategies. Attenuation of the fibrotic process remains an unmet
goal but the potential to prevent damage by promoting tissue repair has been
shown in preclinical studies. Translation of these findings into clinical
practice will hopefully establish new therapeutic options and improve prognosis
of these patients, for which our therapeutic armamentarium remains poor.
PMID- 25850768
TI - Cancer drug discovery targeting histone methyltransferases: an update.
AB - Epigenetic dysregulation has been recognized as an important contributor to
cancer initiation and progression as most tumors harbor both genetic and
epigenetic abnormalities. Inhibiting epigenetic proteins represents a novel
approach in cancer drug discovery and more profound efficacy and less resistance
are expected since multiple signaling pathways can be modulated as a result of
inhibiting a single epigenetic target. Histone methyl transferases (HMTs) are an
important component in epigenome and HMT inhibitors are being pursued intensely
by both pharmaceutical industry and academic institutions. In this article we
will provide an update on the drug discovery effort on several key HMTs.
PMID- 25850769
TI - Selection of Potential Pharmacological Targets in ALS Based on Whole- Genome
Expression Profiling.
AB - Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by the gradual
degeneration and death of upper and lower motor neurons. Despite continue
efforts, the etiology and pathogenesis of ALS are not well understood yet. The
lack of knowledge about molecular and cellular players involved in the
neurodegenerative progression of ALS hinders effective therapy development.
Several genomicbased studies have been conducted to identify genetic contributors
to sporadic ALS (SALS) and new potential pharmacological targets, but these have
resulted in short and non-overlapping lists of candidates. In the last few years,
our research group has developed the largest whole-genome expression profile
database of SALS human samples. We have identified several genes deregulated in
the motor cortex of SALS patients and analyzed the role of these genes within
deregulated pathways, providing a full molecular portrait of ALS pathogenesis.
Some of deregulated genes encode for proteins that are direct or indirect targets
of experimental or therapeutic drugs already applied to unrelated diseases. In
this review, we focus on the potential role of candidate targets in ALS
pathophysiology, highlighting their possible contribution to ALS therapy. The
rational selection of the most promising drug targets and related modulatory
drugs may provide a starting point for their preclinical or clinical validation
and, hopefully, the development of more effective treatments for ALS patients.
PMID- 25850770
TI - Tuberculosis: An Inorganic Medicinal Chemistry Perspective.
AB - Tuberculosis (TB) which is caused by the resilient pathogen Mycobacterium
tuberculosis (MTB) has re-emerged to become a leading public health problem in
the world. The growing number of multi-drug resistant MTB strains and the more
recently emerging problem with the extensively drug resistant strains of the
pathogen are greatly undermining conventional anti-TB therapeutic strategies
which are lengthy and expose patients to toxicity and other unwanted side
effects. The search for new anti-TB drugs essentially involves either the
repurposing of existing organic drugs which are now off patent and already FDA
approved, the synthesis of modified analogues of existing organic drugs, with the
aim of shortening and improving drug treatment for the disease, or the search for
novel structures that offer the possibility of new mechanisms of action against
the mycobacterium. Inorganic medicinal chemistry offers an alternative to organic
drugs through opportunities for the design of therapeutics that target different
biochemical pathways. The incorporation of metal ions into the molecular
structure of a potential drug offers the medicinal chemist an opportunity to
exploit structural diversity, have access to various oxidation states of the
metal and also offer the possibility of enhancing the activity of an established
organic drug through its coordination to the metal centre. In this review, we
summarize what is currently known about the antitubercular capability of metal
complexes, their mechanisms of action and speculate on their potential
applications in the clinic.
PMID- 25850771
TI - Insights into Ecto-5'-Nucleotidase as a New Target for Cancer Therapy: A
Medicinal Chemistry Study.
AB - Ecto-5'-nucleotidase (ecto-5'-NT, 5'-NT, eN, CD73) is a membrane ecto-enzyme that
is primarily responsible for the extracellular production of adenosine from AMP.
Ecto-5'-NT is over expressed in various types of cancer cells, leading to
elevated concentrations of adenosine in the tumor microenvironment. Adenosine has
also been found to be important in cancer pathogenesis, showing strong
immunosuppressive effects over antitumor T cells and macrophages and promoting
neovascularization and cell adherence. These actions support tumor growth and
development. It has been suggested that the inhibition of ecto-5'-NT results in
lower extracellular concentrations of adenosine within the tumor
microenvironment, which would directly affect cancer cells and render malignant
cells more susceptible to host defense systems. Such mechanisms are proposed to
represent promising new targets for cancer therapy. The aim of this review is to
explore the biochemical and structural features of ecto-5'-NT, including a brief
analysis of its active site by molecular modeling, as a means of evaluating
whether the inhibition of this enzyme does indeed represent a feasible strategy
for treating cancer. Known inhibitors and possible prototypes that could be used
to target ecto-5'-NT during cancer therapy are also discussed.
PMID- 25850772
TI - Founding of the society for cardiovascular pathology, inc.
PMID- 25850773
TI - Analysis of formalin-fixed and frozen myocardial autopsy samples for viral genome
in childhood myocarditis and dilated cardiomyopathy with endocardial
fibroelastosis using polymerase chain reaction (PCR).
AB - Viral infection of the myocardium is implicated in the pathogenesis of
myocarditis and dilated cardiomyopathy (DCM). Enteroviruses have been considered
the most common viral etiologic agents, based on peripheral culture and serologic
methods. Recently, polymerase chain reaction (PCR) has been shown to be useful in
the detection of viral genomes from various infected organs and body fluids. In
this study, myocardial samples from autopsy specimens (formalin fixed and fresh
frozen) were examined for enteroviral and DNA viral (adenovirus, herpes simplex
virus [HSV], and cytomegalovirus (CMV]) genome by PCR. The specimens studied were
from 58 patients with myocarditis, 28 patients with DCM and endocardial
fibroelastosis [EFE], and 22 controls. Viral genome was detectable in 34 of the
58 (59%) autopsy-proven myocarditis samples (18 adenovirus, 12 enterovirus, 2
CMV, 2 HSV) and 6 of the 28 samples from patients with DCM and EFE (6
adenovirus). We conclude that PCR is effective in the rapid amplification of
virus from frozen and formalin-fixed myocardial samples and that adenovirus is an
important etiologic agent in viral myocarditis as well as DCM with EFE.
PMID- 25850774
TI - Acute vascular (humoral) rejection in non-OKT3-treated cardiac transplants.
AB - To determine the incidence and morphologic features of acute vascular rejection
(AVR) in cardiac transplant patients who have not received OKT3 induction
therapy, we performed immunofluorescence (IF) staining for Clq and C3c on 341
endomyocardial biopsies from 135 patients. Each AVR biopsy, defined by positive
IF, was further evaluated for C4c, C5, IgG, IgM, and IgA. Light and electron
microscopy were also performed. The clinical features of each case were reviewed.
A total of 29 biopsies from 6 recently transplanted patients (1993) and 10
biopsies from 4 long-term transplants (pre-1993) had IF evidence of AVR. All
patients with AVR had linear vascular deposits of various complement components
and immunoglobulins. Of the 6 recently transplanted patients, 4 were multiparous
females. The male had a single episode of AVR. IF patterns were variable between
and within patients. Clq and C3c were the most consistently detected complement
components. IgM was the most frequently detected antibody. Of the 10 cases of
AVR, 6 occurred within the first month post-transplant. Myocyte necrosis was
present in all cases with cardiac dysfunction. Patients with early onset AVR had
more recurrences and one fatality. There was one fatality in the long-term
transplant group. Concomitant grades 0 to 4+ cellular rejection did not correlate
with results of IF or clinical severity. The incidence of AVR in non-OKT3-treated
patients is 7%. Of the early onset patients, 66% are multiparous females,
indicating the possible importance of prior sensitization. IF patterns are not
predictive of outcome. AVR may be asymptomatic, but early onset predicts a
difficult clinical course and is detected only by IF screening.
PMID- 25850775
TI - Histological changes in the left and right ventricle in hearts with Ebstein's
malformation and tricuspid valvar dysplasia: A morphometric study of patients
dying in the fetal and perinatal periods.
AB - Both Ebstein's malformation and the related tricuspid valvar dysplasia are often
associated with tricuspid regurgitation, and impaired right ventricular function
may develop. Impaired function of the left ventricle in Ebstein's malformation
has also been described. Interstitial fibrosis has been shown in the right and
left ventricles of hearts with Ebstein's malformation from neonates, children,
and adults. The objective of this study was to determine whether interstitial
fibrosis seen in Ebstein's malformation is an intrinsic part of the congenital
malformation or is acquired. From the fetal and perinatal periods, we compared 13
hearts with Ebstein's malformation (6 isolated and 7 with additional
abnormalities) and 11 with tricuspid valvar dysplasia (3 isolated and 8 with
additional abnormalities) with 16 controls. Three adult cases of isolated
Ebstein's malformation in patients aged 17 to 20 years, were compared with 5
controls. The percentage of interstitial fibrous tissue and the thickness of the
endocardium in the right and left ventricles were measured using
histomorphometry. There were similar findings in Ebstein's malformation and
tricuspid valvar dysplasia. Of 24 fetal and perinatal cases, 23 had normal
interstitial fibrous tissue. Interstitial fibrosis was found in the right
ventricle of only 1 perinatal heart with Ebstein's malformation and pulmonary
stenosis. Of the 9 fetal cases, 4 had minimal right ventricular endocardial
thickening (up to 10 MUm). The left ventricular endocardium was normal in this
group. Of the 6 perinatal cases with isolated Ebstein's malformation or tricuspid
valvar dysplasia, 4 had right and 2 had left ventricular endocardial thickening
(up to 345 MUm). Of the 3 adult hearts with Ebstein's malformation, 2 had right
ventricular endocardial thickening (47 and 225 MUm) and 2 had right and 1 had
left ventricular interstitial fibrosis. These results indicate that in both
Ebstein's malformation and tricuspid valvar dysplasia the endocardial thickening
develops in perinatal life, and in Ebstein's malformation the interstitial
fibrosis develops in later life.
PMID- 25850776
TI - Ebstein's malformation-What's in a name?
PMID- 25850777
TI - Chronic ischemic viable myocardium in man: Aspects of dedifferentiation.
AB - Histologic analysis of biopsies derived from patients with chronic dysfunctional
but viable (hibernating) myocardium showed characteristic cell alterations. These
changes consisted of a partial to complete loss of sarcomeres, accumulation of
glycogen, and disorganization and loss of sarcoplasmic reticulum. Most of the
adaptive changes that these affected cells undergo are suggestive of
dedifferentiation. In the present study the expression and organizational pattern
of contractile and cytoskeletal proteins such as titin, cardiotin, and alpha
smooth muscle actin were assessed in hibernating and normal myocardium because
the expression and organization of these constituents have been related to
certain stages of cardiomyocyte differentiation. In normal cells titin shows a
cross-striated staining pattern, whereas cardiotin displays a fibrillar array,
parallel to the sarcomeres. alpha-Smooth muscle actin is not expressed in adult
cardiomyocytes. The expression of titin in a punctated pattern and the marked
decrease to virtual absence of cardiotin in hibernating cardiomyocytes speak in
favor of an embryonic phenotype of these cells. The re-expression of alpha-smooth
muscle actin in hibernating cells strongly supports this hypothesis. The
observations on three different structural proteins of heart muscle suggest that
hibernating myocardium acquired aspects of muscle cell dedifferentiation.
PMID- 25850778
TI - Amyloidosis and endomyocardial biopsy: Correlation of extent and pattern of
deposition with amyloid immunophenotype in 100 cases.
AB - The heart is subject to involvement by primary (AL), senile (AS), and familial
(AF) forms of amyloidosis, but the frequency, severity, and therapy of amyloid
related cardiac symptoms differ depending on the type of amyloidosis present.
Endomycardial biopsy is a safe and reliable procedure for diagnosing cardiac
amyloidosis, and immunohistochemical staining of routinely processed biopsy
specimens can be performed to classify the type of amyloid present. However,
whether or not the type can be determined from the histologic extent and pattern
of amyloid deposition is unclear. Endomyocardial biopsy specimens from 100
patients with cardiac amyloidosis (74 AL, 22 AS, 4 AF) were examined, and the
histologic extent and pattern of amyloid deposition were correlated with the
amyloid immunophenotype. No difference in the extent of amyloid deposition was
identified among the three types. Interstitial nodules of amyloid were more
common in AS (82%) than in AL (50%, p = 0.0129), whereas vascular involvement was
more frequently observed in AL (88%) than in AS (26%, p < 0.0001). Endocardial
and interstitial pericellular deposition occurred with similar frequencies in
both groups. Although statistically significant differences existed in the
patterns of amyloid deposition, they did not allow reliable distinction between
the different types in individual cases. Consequently, in older patients without
serum or urinary light chains, immunohistochemical staining is recommended to
distinguish AL from AS types of amyloid in cardiac biopsy tissues.
PMID- 25850779
TI - Eosinophilic myocarditis in patients waiting for heart transplantation.
AB - We report three patients waiting for heart transplantation who suddenly worsened
clinically. All three explanted hearts showed a myocarditis with a dense
eosinophilic infiltrate. Follow-up biopsies and necropsies showed no further
evidence of cardiac eosinophilic infiltrates. The possible relationship between
drugs administered before transplantation and clinico-pathological findings is
discussed.
PMID- 25850780
TI - Right ventricular dysplasia: Right and left ventricular involvement
morphometrically evaluated.
AB - Right ventricular dysplasia (RVD) is a cardiac anomaly characterized by
replacement of variable amounts of right ventricular myocardium by adipose
tissue. This condition is believed to be a selective disorder involving
extensively the right ventricle, but there are occasional reports of concomitant
"minor" abnormalities of the left ventricle. The object of this report concerns a
patient who died after heart transplantation because of an unsuspected RVD of the
donor heart. We present a morphometric study of the heart in order to evaluate
the distribution of the fat on both ventricles and to understand the structural
basis of the heart failure. The results show that a large portion of the right
ventricle is replaced by fat with a quite homogeneous distribution; the left
ventricle is also largely replaced by adipose tissue that is primarily localized
at the apex and decreases from the apex to the basis. The remodeling of the heart
is attributable to a conspicuous increase in volume of the right ventricle
associated with a normal number of myocytes that are longer than normal. For
these reasons, according to Starling's law, the heart develops congestive
failure.
PMID- 25850781
TI - Fibronectin accumulation within cardiac myocytes in rats with elevated plasma
angiotensin II.
AB - Elevation in plasma angiotensin II (AngII) is associated with cardiac myocyte
necrosis. Myocyte necrosis followed by wound healing and fibrosis represents a
structural remodeling of the myocardium thought to contribute to abnormal
myocardial function. Fibronectin (FN) is generally considered an early component
of the healing process that precedes collagen accumulation. To better understand
the time course of this remodeling process involving both cardiac myocytes and
extracellular matrix, (i.e., FN and collagen), we used two animal models: (1)
endogenous activation of the renin-angiotensin system by surgical induction of
renovascular hypertension and (2) exogenous AngII administration (150 ng/min/kg).
Animals were killed at different time points within the first two weeks. Both
"cellular" (cFN) and "plasma" (pFN) FN immunolabeling were compared with collagen
distribution (picrosirius red stain), together with histopathologic (hematoxylin
eosin stain) and ultrastructural examination of cardiac myocytes. In each
experimental group, the pattern and time course of FN immunolabeling was
coincident with histopathologic evidence of myocyte injury and/or remodeling. We
found different patterns of FN labeling of cardiac myocytes: (a) homogenous
intracellular distribution in necrotic myocytes, most obvious on days 1 and 2;
(b) patchy intracellular distribution in nonnecrotic myocytes starting on day 4;
and (c) marking internalized capillaries. Both FNs were codistributed throughout
the myocardium of each ventricle; however, cFN was less pronounced and not seen
in mature scars. Ultrastructural examination revealed different kinds of
intramyocytic inclusions, characterized by vacuoles containing
fibrillar/flocculent material, remnants of unknown origin, or internalized
capillaries. We conclude that FNs are markers of cardiac myocyte necrosis and
early interstitial remodeling and that renovascular hypertension and AngII
administration exhibit the same time course and pattern of FN and collagen
expression.
PMID- 25850782
TI - Ostial stenosis of the left main coronary artery in a young woman 10 years after
radiation therapy.
AB - A 26-year-old woman developed critical stenosis of the left main coronary artery
10 years after radiation treatment for Hodgkins disease. She was operated on but
died in the immediate postoperative period. At autopsy the pathological findings
were indistinguishable from those described in "typical" atherosclerotic plaques.
PMID- 25850783
TI - Making the most of what we have: application of extrapolation approaches in
radioecological wildlife transfer models.
AB - We will never have data to populate all of the potential radioecological
modelling parameters required for wildlife assessments. Therefore, we need robust
extrapolation approaches which allow us to make best use of our available
knowledge. This paper reviews and, in some cases, develops, tests and validates
some of the suggested extrapolation approaches. The concentration ratio
(CRproduct-diet or CRwo-diet) is shown to be a generic (trans-species) parameter
which should enable the more abundant data for farm animals to be applied to wild
species. An allometric model for predicting the biological half-life of
radionuclides in vertebrates is further tested and generally shown to perform
acceptably. However, to fully exploit allometry we need to understand why some
elements do not scale to expected values. For aquatic ecosystems, the
relationship between log10(a) (a parameter from the allometric relationship for
the organism-water concentration ratio) and log(Kd) presents a potential
opportunity to estimate concentration ratios using Kd values. An alternative
approach to the CRwo-media model proposed for estimating the transfer of
radionuclides to freshwater fish is used to satisfactorily predict activity
concentrations in fish of different species from three lakes. We recommend that
this approach (REML modelling) be further investigated and developed for other
radionuclides and across a wider range of organisms and ecosystems. Ecological
stoichiometry shows potential as an extrapolation method in radioecology, either
from one element to another or from one species to another. Although some of the
approaches considered require further development and testing, we demonstrate the
potential to significantly improve predictions of radionuclide transfer to
wildlife by making better use of available data.
PMID- 25850784
TI - Independent and Combined Associations of Physical Activity and Sedentary Behavior
with Depressive Symptoms Among Japanese Adults.
AB - BACKGROUND: Associations between levels of sedentary behavior and depressive
symptoms independently and in combination with different levels of physical
activity remain unclear. PURPOSE: This study aimed to examine independent and
combined associations of physical activity (PA) and sedentary behavior (SB) with
depressive symptoms among Japanese adults. METHOD: An Internet-based survey
collected data on depression levels (Center for Epidemiologic Studies Depression
Scale), self-reported time spent in PA and SB (Japanese short version of the
International Physical Activity Questionnaire), and sociodemographic variables
from 2,914 adults in 2009. Binary logistic regression analyses were conducted to
examine the odds ratios (ORs) for being depressed (depression scores >=16)
according to independent PA levels (none, insufficient, sufficient), SB levels
(low, moderate, high), and nine combinations of PA and SB categories. RESULTS:
After adjusting for potential confounders, sufficient PA level was found to be
related to lower risk of depressive symptoms independently (OR = 0.61), whereas
no significant associations were observed between SB levels and depression. In
the combined associations, adults in the sufficient PA/high SB (OR = 0.44),
sufficient PA/moderate SB (OR = 0.56), and sufficient PA/low SB (OR = 0.57)
categories were significantly less likely to have depressive symptoms in
comparison with the no PA/high SB category. CONCLUSION: Meeting physical activity
recommendations is associated with a lower risk of depressive symptoms,
regardless of time spent in total sedentary behavior. These results suggest that
promoting physical activity may be an effective strategy against depressive
symptoms among Japanese adults.
PMID- 25850786
TI - [Molecular pathogenesis of thyroid tumors].
AB - The molecular pathogenesis of thyroid tumors has been an evolving field in the
past years. The constitutive activation of intracellular tyrosine kinases has
been identified as a hallmark of thyroid cancer. The activation of MAPK and PI3K
pathways through somatic gene mutations or gene rearrangements seem to play a
pivotal role in the pathogenesis of follicular-cell-derived tumors. In poorly
differentiated tumors and anaplastic tumors often an accumulation of genetic
alterations from differentiated thyroid cancer but also novel gene mutations can
be observed. The C-cell-derived medullary thyroid cancer evolves through the
constitutive activation of the RET kinase, either through germline RET mutations
or somatic RET and RAS mutations. The better knowledge of the molecular
pathogenesis allowed the development of targeted therapies in thyroid cancer
patients. The identification of molecular response markers to tyrosine kinase
inhibitor therapy is desirable.
PMID- 25850789
TI - The human hookworm vaccine: recent updates and prospects for success.
AB - Approximately 440 million people globally are afflicted by hookworm disease, one
of the 17 WHO-recognized neglected tropical diseases (NTDs). The iron-deficiency
anaemia attributed to this disease contributes to at least 3.2 million disability
adjusted life years (DALYs) according to the Global Burden of Disease Study 2010.
The current WHO-recommended control strategies rely primarily on mass drug
administration or preventive chemotherapy. However, evidence is starting to
accumulate confirming that preventive chemotherapy alone will not be sufficient
to reduce the reinfection rates of hookworm, especially in areas of heavy
transmission. The global health and research community is currently building a
consensus stressing the need for the advancement of research and innovation to
bridge the gaps and identify new public health interventions for diseases such as
hookworm and other NTDs. This paper presents the strategies used by the Sabin
Vaccine Institute Product Development Partnership (Sabin PDP) in their ongoing
endeavour for the development of a human hookworm vaccine. Recent updates and the
current prospects for success of an effective human hookworm vaccine, as a new
technology to be linked to or combined with drug interventions, are presented.
PMID- 25850787
TI - SIRT1 and Neural Cell Fate Determination.
AB - During the development of the central nervous system (CNS), neurons and glia are
derived from multipotent neural stem cells (NSCs) undergoing self-renewal. NSC
commitment and differentiation are tightly controlled by intrinsic and external
regulatory mechanisms in space- and time-related fashions. SIRT1, a silent
information regulator 2 (Sir2) ortholog, is expressed in several areas of the
brain and has been reported to be involved in the self-renewal, multipotency, and
fate determination of NSCs. Recent studies have highlighted the role of the
deacetylase activity of SIRT1 in the determination of the final fate of NSCs.
This review summarizes the roles of SIRT1 in the expansion and differentiation of
NSCs, specification of neuronal subtypes and glial cells, and reprogramming of
functional neurons from embryonic stem cells and fibroblasts. This review also
discusses potential signaling pathways through which SIRT1 can exhibit versatile
functions in NSCs to regulate the cell fate decisions of neurons and glia.
PMID- 25850788
TI - Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic
bottleneck.
AB - Human infection with avian influenza A(H7N9) virus is associated mainly with the
exposure to infected poultry. The factors that allow interspecies transmission
but limit human-to-human transmission are unknown. Here we show that
A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is
asymptomatic and that it generates a high genetic diversity. In contrast,
diversity is tightly restricted in infected ferrets, limiting further adaptation
to a fully transmissible form. Airborne transmission in ferrets is accompanied by
the mutations in PB1, NP and NA genes that reduce viral polymerase and
neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals,
further adaptation appears to incur a fitness cost. Our results reveal that a
tight genetic bottleneck during avian-to-mammalian transmission is a limiting
factor in A(H7N9) influenza virus adaptation to mammals. This previously
unrecognized biological mechanism limiting species jumps provides a measure of
adaptive potential and may serve as a risk assessment tool for pandemic
preparedness.
PMID- 25850790
TI - Stone formation and management after bariatric surgery.
AB - Obesity is a significant health concern and is associated with an increased risk
of nephrolithiasis, particularly in women. The underlying pathophysiology of
stone formation in obese patients is thought to be related to insulin resistance,
dietary factors, and a lithogenic urinary profile. Uric acid stones and calcium
oxalate stones are common in these patients. Use of surgical procedures for
obesity (bariatric surgery) has risen over the past two decades. Although such
procedures effectively manage obesity-dependent comorbidities, several large,
controlled studies have revealed that modern bariatric surgeries increase the
risk of nephrolithiasis by approximately twofold. In patients who have undergone
bariatric surgery, fat malabsorption leads to hyperabsorption of oxalate, which
is exacerbated by an increased permeability of the gut to oxalate. Patients who
have undergone bariatric surgery show characteristic 24 h urine parameters
including low urine volume, low urinary pH, hypocitraturia, hyperoxaluria and
hyperuricosuria. Prevention of stones with dietary limitation of oxalate and
sodium and a high intake of fluids is critical, and calcium supplementation with
calcium citrate is typically required. Potassium citrate is valuable for treating
the common metabolic derangements as it raises urinary pH, enhances the activity
of stone inhibitors, reduces the supersaturation of calcium oxalate, and corrects
hypokalaemia. Both pyridoxine and probiotics have been shown in small studies to
reduce hyperoxaluria, but further study is necessary to clarify their effects on
stone morbidity in the bariatric surgery population.
PMID- 25850791
TI - Prostate cancer: New gene panel for aggressive prostate cancer.
PMID- 25850793
TI - Therapy: Are long-acting intramuscular testosterone injections safe?
PMID- 25850792
TI - Current understanding of hypospadias: relevance of animal models.
AB - Hypospadias is a congenital abnormality of the penile urethra with an incidence
of approximately 1:200-1:300 male births, which has doubled over the past three
decades. The aetiology of the overwhelming majority of hypospadias remains
unknown but appears to be a combination of genetic susceptibility and prenatal
exposure to endocrine disruptors. Reliable animal models of hypospadias are
required for better understanding of the mechanisms of normal penile urethral
formation and hence hypospadias. Mice and/or rats are generally used for
experimental modelling of hypospadias, however these do not fully reflect the
human condition. To use these models successfully, researchers must understand
the similarities and differences between mouse, rat and human penile anatomy as
well as the normal morphogenetic mechanisms of penile development in these
species. Despite some important differences, numerous features of animal and
human hypospadias are shared: the prevalence of distal penile malformations;
disruption of the urethral meatus; disruption of urethra-associated erectile
bodies; and a common mechanism of impaired epithelial fusion events. Rat and
mouse models of hypospadias are crucial to our understanding of hypospadias to
ultimately reduce its incidence through better preventive strategies.
PMID- 25850794
TI - Sexual dysfunction: Anandamide shows promise for lifelong delayed ejaculation.
PMID- 25850796
TI - Sexual dysfunction: Blue light, not blue pills, for erectile dysfunction.
PMID- 25850797
TI - Prostate cancer: New biomarker panel prognosticates patient survival.
PMID- 25850798
TI - Urinary incontinence: Propagating contractions influence urinary bladder tone.
PMID- 25850799
TI - Microengineered peripheral nerve-on-a-chip for preclinical physiological testing.
AB - The use of advanced in vitro testing is a powerful tool to develop predictive
cellular assays suitable for improving the high attrition rates of novel
pharmaceutical compounds. A microscale, organotypic model of nerve tissue with
physiological measures that mimic clinical nerve compound action potential (CAP)
and nerve fiber density (NFD) tests may be more predictive of clinical outcomes,
enabling a more cost-effective approach for selecting promising lead compounds
with higher chances of late-stage success. However, the neurological
architecture, physiology, and surrounding extracellular matrix are hard to mimic
in vitro. Using a dual hydrogel construct and explants from rat embryonic dorsal
root ganglia, the present study describes an in vitro method for
electrophysiological recording of intra- and extra-cellular recordings using a
spatially-controlled, microengineered sensory neural fiber tract. Specifically,
these 3D neural cultures exhibit both structural and functional characteristics
that closely mimic those of afferent sensory peripheral fibers found in vivo. Our
dual hydrogel system spatially confines growth to geometries resembling nerve
fiber tracts, allowing for a high density of parallel, fasciculated neural
growth. Perhaps more importantly, outputs resembling clinically relevant test
criteria, including the measurement of CAP and NFD are possible through our
advanced model. Moreover, the 3D hydrogel constructs allow flexibility in
incorporated cell type, geometric fabrication, and electrical manipulation,
providing a viable assay for systematic culture, perturbation, and testing of
biomimetic neural growth for mechanistic studies necessitating physiologically
relevant readouts.
PMID- 25850805
TI - Liposomes as novel anti-infectives targeting bacterial virulence factors?
AB - A recent report commissioned by Prime Minister David Cameron and chaired by
former Goldman Sachs chief economist Jim O'Neill warns that the emergence,
persistence and spread of antimicrobial resistance could lead to 10 million
deaths per year and cause an economic burden as much as US$100 trillion by 2050.
In the midst of this global crisis, unprecedented paths are being explored to
combat bacterial infection. Virulence factors, and more particularly pore-forming
toxins, play a key role in increasing morbidity and mortality caused by drug
resistant bacterial infections. Novel anti-infective liposomes specifically
targeting and neutralizing these cytotoxic toxins are potential game-changers in
the fight against deadly infections.
PMID- 25850800
TI - Flexibility decline contributes to similarity of past and future thinking in
Alzheimer's disease.
AB - A striking similarity has been suggested between past and future thinking in
Alzheimer's Disease (AD), a similarity attributable to abnormalities in common
modular cognitive functions and neuroanatomical substrates. This study extends
this literature by identifying specific executive function deficits underlying
past and future thinking in AD. Twenty-four participants with a clinical
diagnosis of probable (mild) AD and 26 older controls generated past and future
events and underwent tests of binding and the executive functions of flexibility,
inhibition, and updating. AD patients showed similar autobiographical
performances in past and future event generation, and so did control
participants. In each group, the similarity of past and future thinking was
predicted by flexibility. Furthermore, AD patients with low flexibility showed
higher similarity of past and future thinking than those with high flexibility.
These findings are interpreted in terms of involvement of the hippocampus and
frontal lobes in future thinking. Deficits in these brain regions in AD are
likely to compromise the ability to recombine episodic information into novel and
flexible configurations as scenarios for the future.
PMID- 25850806
TI - Community-acquired Acinetobacter baumannii: clinical characteristics,
epidemiology and pathogenesis.
AB - Community-acquired Acinetobacter baumannii (CA-Ab) is a rare but serious cause of
community-acquired pneumonia in tropical regions of the world. CA-Ab infections
predominantly affect individuals with risk factors, which include excess alcohol
consumption, diabetes mellitus, smoking and chronic lung disease. CA-Ab pneumonia
presents as a surprisingly fulminant course and is characterized by a rapid onset
of fever, severe respiratory symptoms and multi-organ dysfunction, with a
mortality rate reported as high as 64%. It is unclear whether the distinct
clinical syndrome caused by CA-Ab is because of host predisposing factors or
unique bacterial characteristics, or a combination of both. Deepening our
understanding of the drivers of overwhelming CA-Ab infection will provide
important insights into preventative and therapeutic strategies.
PMID- 25850807
TI - Electron transfer budgets and kinetics of abiotic oxidation and incorporation of
aqueous sulfide by dissolved organic matter.
AB - The reactivity of natural dissolved organic matter toward sulfide and has not
been well studied with regard to electron transfer, product formation, and
kinetics. We thus investigated the abiotic transformation of sulfide upon
reaction with reduced and nonreduced Sigma-Aldrich humic acid (HA), at pH 6 under
anoxic conditions. Sulfide reacted with nonreduced HA at conditional rate
constants of 0.227-0.325 h(-1). The main transformation products were elemental S
(S0) and thiosulfate (S2O3(2-)), yielding electron accepting capacities of 2.82
1.75 MUmol e- (mg C)(-1). Native iron contents in the HA could account for only 6
9% of this electron transfer. About 22-37% of S reacted with the HA to form
organic S (Sorg). Formation of Sorg was observed and no inorganic transformation
products occurred for reduced HA. X-ray absorption near edge structure
spectroscopy supported Sorg to be mainly zerovalent, such as thiols, organic di-
and polysulfides, or heterocycles. In conclusion, our results demonstrate that HA
can abiotically reoxidize sulfide in anoxic environments at rates competitive to
sulfide oxidation by molecular oxygen or iron oxides.
PMID- 25850809
TI - Low-Temperature Cathodoluminescence Investigations of High-Quality Zinc Oxide
Nanorods.
AB - We present results of cathodoluminescence (CL) investigations of high-quality
zinc oxide (ZnO) nanorods obtained by an extremely fast hydrothermal method on a
silicon substrate. A scanning electron microscopy (SEM) system equipped with CL
allows direct comparison of SEM images and CL maps, taken from exactly the same
areas of samples. Investigations are performed at a temperature of 5 K. An
interlink between sample microstructure and emission properties is investigated.
CL confirms a very high quality of ZnO nanorods produced by our method. In
addition, the presence of super radiation effects in ZnO nanorod arrays is
suggested.
PMID- 25850808
TI - Rice FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (OsFKF1) promotes flowering
independent of photoperiod.
AB - In the facultative long-day (LD) plant Arabidopsis thaliana, FLAVIN-BINDING,
KELCH REPEAT, F-BOX 1 (FKF1) is activated by blue light and promotes flowering
through the transcriptional and post-translational regulation of CONSTANS under
inductive LD conditions. By contrast, the facultative short day (SD) plant rice
(Oryza sativa) flowers early under inductive SD and late under non-inductive LD
conditions; the regulatory function of OsFKF1 remains elusive. Here we show that
osfkf1 mutants flower late under SD, LD and natural LD conditions.
Transcriptional analysis revealed that OsFKF1 up-regulates the expression of the
floral activator Ehd2 and down-regulates the expression of the floral repressor
Ghd7; these regulators up- and down-regulate Ehd1 expression, respectively.
Moreover, OsFKF1 can up-regulate Ehd1 expression under blue light treatment,
without affecting the expression of Ehd2 and Ghd7. In contrast to the LD-specific
floral activator Arabidopsis FKF1, OsFKF1 likely acts as an autonomous floral
activator because it promotes flowering independent of photoperiod, probably via
its distinct roles in controlling the expression of rice-specific genes including
Ehd2, Ghd7 and Ehd1. Like Arabidopsis FKF1, which interacts with GI and CDF1,
OsFKF1 also interacts with OsGI and OsCDF1 (also termed OsDOF12). Thus, we have
identified similar and distinct roles of FKF1 in Arabidopsis and rice.
PMID- 25850811
TI - A survey of nitrate and nitrite concentrations in conventional and organic
labeled raw vegetables at retail.
AB - A national survey of the nitrate ( NO3(-)) and nitrite ( NO2(-)) concentrations
in raw and highly consumed vegetables available at retail in the United States
was conducted. A total of 194 samples of fresh broccoli, cabbage, celery,
lettuce, and spinach categorized as conventional or organic by label were
collected from 5 major cities in different geographic regions of the United
States and analyzed to determine NO3(-) and NO2(-) concentrations. There were no
differences in the mean NO2(-) values of conventional compared with organic
vegetables taken from the 5 metropolitan areas. However, significant differences
in mean pairwise comparisons between some conventional and organic vegetables for
NO3(-) content were observed. The mean NO2(-) concentration of both conventional
and organic vegetables ranged between 0.1 and 1.2 mg/kg of fresh weight (FW) with
the exception of conventional spinach that contained 8.0 mg/kg FW. Mean NO3(-)
contents of conventional broccoli, cabbage, celery, lettuce, and spinach were
394, 418, 1496, 851, and 2797 mg/kg FW, respectively, while their organic-labeled
counterparts averaged 204, 552, 912, 844, and 1318 mg/kg FW. In most cases,
organic vegetables were numerically lower in NO3(-) content than their
conventional counterparts. Based on survey results, the finding that low NO3(-)
levels were observed in some organic vegetables in different cities may warrant
further study to determine if true differences exist, due to production
practices, seasonal differences, and the magnitudes of those differences.
Furthermore, the geographic differences in NO3(-) content of vegetables may flaw
estimates of daily NO2(-) and NO3(-) exposure.
PMID- 25850812
TI - Characterization of the 1,1-HF Elimination Reaction from the Competition between
the 1,1-HF and 1,2-DF Unimolecular Elimination Reactions of CD3CD2CHF2.
AB - The recombination of CHF2 and C2D5 radicals was used to produce CD3CD2CHF2*
molecules with 96 kcal mol(-1) of vibrational energy in a room temperature bath
gas. The formation of CD3CD?CHF and CD3CD?CDF was used to identify the 1,2-DF and
1,1-HF unimolecular elimination channels; CD3CD?CDF is formed by isomerization of
the singlet-state CD3CD2CF carbene. The total unimolecular rate constant is 1.6 *
10(6) s(-1), and the branching ratio for 1,1-HF elimination is 0.25. Threshold
energies of 64 +/- 2 and 73 +/- 2 kcal mol(-1) were assigned to the 1,2-DF and
1,1-HF reaction channels. The E and Z isomers of 1-fluoropropene were observed
for each reaction; approximately 30% of the CD3CD?CDF molecules derived from 1,1
HF elimination retained enough energy to undergo cis-trans isomerization.
Electronic structure calculations with density-functional theory were used to
characterize the transition-state structures and the H atom migration barrier for
CD3CD2CF. Adjustment of the rate constants to account for kinetic-isotope effects
suggest that the branching ratio would be 0.20 for 1,1-HF elimination from
C2H5CHF2. The results from an earlier study of CD3CHF2 and CH3CHF2 are also
reinterpreted to assign a threshold energy of 74 kcal mol(-1) for the 1,1-HF
elimination reaction. Because CHF2CHF2* is generated in the photolysis system,
the 1,1-and 1,2-HF-elimination reactions of CHF2CHF2* are discussed. The 1,1-HF
channel was identified by trapping the CF2HCF carbene with cis-butene-2.
PMID- 25850810
TI - Human B-cell and progenitor stages as determined by probability state modeling of
multidimensional cytometry data.
AB - BACKGROUND: Human progenitor and B-cell development is a highly regulated process
characterized by the ordered differential expression of numerous cell-surface and
intracytoplasmic antigens. This study investigates the underlying coordination of
these modulations by examining a series of normal bone marrow samples with the
method of probability state modeling or PSM. RESULTS: The study is divided into
two sections. The first section examines B-cell stages subsequent to CD19 up
regulation. The second section assesses an earlier differentiation stage before
and including CD19 up-regulation. POST-CD19 ANTIGENIC UP-REGULATION: Statistical
analyses of cytometry data derived from sixteen normal bone marrow specimens
revealed that B cells have at least three distinct coordinated changes, forming
four stages labeled as B1, B2, B3, and B4. At the end of B1; CD34 antigen
expression down-regulates with TdT while CD45, CD81, and CD20 slightly up
regulate. At the end of B2, CD45 and CD20 up-regulate. At the end of B3 and
beginning of B4; CD10, CD38, and CD81 down-regulate while CD22 and CD44 up
regulate. PRE-CD19 ANTIGENIC UP-REGULATION: Statistical analysis of ten normal
bone marrows revealed that there are at least two measurable coordinated changes
with progenitors, forming three stages labeled as P1, P2, and P3. At the end of
P1, CD38 up-regulates. At the end of P2; CD19, CD10, CD81, CD22, and CD9 up
regulate while CD44 down-regulates slightly. CONCLUSIONS: These objective results
yield a clearer immunophenotypic picture of the underlying cellular mechanisms
that are operating in these important developmental processes. Also,
unambiguously determined stages define what is meant by "normal" B-cell
development and may serve as a preliminary step for the development of highly
sensitive minimum residual disease detection systems. A companion article is
simultaneously being published in Cytometry Part A that will explain in further
detail the theory behind PSM. Three short relevant videos are available in the
online supporting information for both of these papers.
PMID- 25850813
TI - ASXL1 mutations are frequent and prognostically detrimental in CSF3R-mutated
chronic neutrophilic leukemia.
AB - Colony stimulating factor 3 receptor gene (CSF3R) mutations have recently been
associated with chronic neutrophilic leukemia (CNL). Fourteen patients with CSF3R
mutated CNL (median age 67 years; 57% males) were screened for additional
mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mutation (two
patients expressed both), respectively. Two patients developed blastic
transformation, both SETBP1-mutated and ASXL1-unmutated, whereas two other cases
evolved into chronic myelomonocytic leukemia (CMML), both ASXL1-mutated and
SETBP1-unmutated. Median survival was 23.2 months (10 deaths documented). On
multivariable analysis mutated ASXL1 (P = 0.009; HR 19.6, 95% CI 2.1-184.1) and
thrombocytopenia (P = 0.005; HR 28.8, 95% CI 2.8-298.2) were independently
predictive of shortened survival. This study provides information on the natural
history of CSF3R-mutated CNL and identifies mutant ASXL1 and thrombocytopenia as
risk factors for survival. The study also suggests pathogenetic roles for SETBP1
and ASXL1 mutations in disease evolution into blast phase disease and CMML,
respectively.
PMID- 25850814
TI - A double-blind randomised controlled trial testing the effect of a barley product
containing varying amounts and types of fibre on the postprandial glucose
response of healthy volunteers.
AB - The aim of the present study was to determine if the consumption of barley
tortillas varying in fibre and/or starch composition affected postprandial
glucose, insulin, glucagon-like peptide-1 (GLP-1) or peptide YY concentrations. A
double-blind, randomised, controlled trial was performed with twelve healthy
adults. They each consumed one of five barley tortillas or a glucose drink on six
individual visits separated by at least 1 week. Tortillas were made from 100%
barley flour blends using five different milling fractions to achieve the desired
compositions. All treatments provided 50 g of available carbohydrate and were
designed to make the following comparisons: (1) low-starch amylose (0%) v. high
starch amylose (42%) with similar beta-glucan and insoluble fibre content; (2)
low beta-glucan (4.5 g) v. medium beta-glucan (7.8 g) v. high beta-glucan (11.6
g) with similar starch amylose and insoluble fibre content; and (3) low insoluble
fibre (7.4 g) v. high insoluble fibre (19.6 g) with similar starch amylose and
beta-glucan content. Blood was collected at fasting and at multiple intervals
until 180 min after the first bite/sip of the test product. Amylose and insoluble
fibre content did not alter postprandial glucose and insulin, but high-beta
glucan tortillas elicited a lower glucose and insulin response as compared to the
low-beta-glucan tortillas. The tortillas with high insoluble fibre had a higher
AUC for GLP-1 as compared to the tortillas with low insoluble fibre, whereas
amylose and beta-glucan content had no effect. Results show that processing
methods can be used to optimise barley foods to reduce postprandial blood glucose
responses and factors that may influence satiety.
PMID- 25850815
TI - Controlling the capture and release of DNA with a dual-responsive cationic
surfactant.
AB - A dual-responsive cationic surfactant, 4-ethoxy-4'-(trimethyl- aminoethoxy)
azobenzene trichloromonobromoferrate (azoTAFe), which contains both a light
responsive moiety azobenzene and a paramagnetic counterion, [FeCl3Br](-), was
designed and synthesized. Not only does this cationic surfactant abundantly
utilize inexhaustible and clean sources, i.e., light and magnetic field, but it
also serves as a powerful dual-switch molecule for effectively controlling the
capture and release of DNA. Our results could provide potential applications in
gene therapy for creating smart and versatile machines to control the transport
and delivery of DNA more intelligently and robustly. It was proved that the light
switch can independently realize a reversible DNA compaction. The introduction of
a magnetic switch can significantly enhance the compaction efficiency, help
compact DNA with a lower dosage and achieve a magnetic field-based targeted
transport of DNA. In addition, the light switch can make up the irreversibility
of magnetic switch. This kind of self-complementation makes the cationic azoTAFe
be useful as a potential tool that can be applied to the field of gene therapy
and nanomedicine.
PMID- 25850816
TI - Ex Vivo Induced Regulatory Human/Murine Mesenchymal Stem Cells as Immune
Modulators.
AB - Over the past decade there has been a growing interest in using mesenchymal stem
cells (MSCs) as an immune-regulatory agent for prevention and treatment of
various immune disorders including graft-versus-host disease (GVHD), transplanted
organ rejection, and autoimmune diseases. However, the high diversity in the
results from clinical trials using MSCs for such disorders emphasizes the need
for MSCs to be "professionalized" ex vivo to a more defined regulatory phenotype
before administering to patients. To this aim, we have established an ex vivo
immunomodulatory triple combination treatment (TCT) for MSCs, using IFNgamma,
TGFbeta, and kynurenine. We show that pretreated MSCs acquire an immunomodulatory
phenotype, have improved regulatory functions, and upregulate the expression of
inducible nitric oxide synthase, indoleamine 2,3-dioxygenase, cyclooxygenase-2
(COX2), heme oxygenase 1, leukemia inhibitory factor (LIF), and programmed death
ligand 1. We define the pathway of kynurenine induced aryl hydrocarbon receptor
activation in MSCs and how it contributes to the upregulation of COX2 expression
and IL-6 downregulation. The combination of reduced IL-6 secretion with enhanced
LIF expression leads to the inhibition of Th17 differentiation in coculture of
TCT MSCs and lymphocytes. To test the immunomodulatory function of TCT MSCs in
vivo, we used the cells as GVHD prophylaxis in a GVHD mouse model. TCT MSCs
administration significantly decreased GVHD score and improved mouse survival.
Importantly, single administration could attenuate disease symptoms for more than
3 weeks. Based on these results, we suggest considering TCT MSCs as an improved
cell therapy for systemic diseases with an underlying inflammatory and
immunologic etiology. Stem Cells 2015;33:2256-2267.
PMID- 25850817
TI - Incidence of intravascular injection and the spread of contrast media during S1
transforaminal epidural steroid injection by two approaches: anteroposterior vs
oblique.
AB - The aim of this randomised study was to compare the incidence of intravascular
injections during S1 transforaminal epidural steroid injection performed in the
anteroposterior and oblique views. We also compared epidural spread patterns of
contrast media, which included 201 injections at the S1 level. The overall
incidence of intravascular injection during S1 transforaminal epidural steroid
injection in the anteroposterior view was 29% (29/99), significantly higher than
in the oblique view (11%, 11/102, p = 0.001). There were no significant
differences between the two groups for epidural spread of contrast media in cases
where intravascular injections did not occur (p = 0.77). Performing S1
transforaminal epidural steroid injection in the oblique view rather than the
anteroposterior view reduces the risk of intravascular injections.
PMID- 25850818
TI - COMPARISON OF CHITIN STRUCTURES DERIVED FROM THREE COMMON WASP SPECIES (Vespa
crabro LINNAEUS, 1758, Vespa orientalis LINNAEUS, 1771 and Vespula germanica
(FABRICIUS, 1793)).
AB - There has been no study on the chitin structure of wasp species. Here, we
selected the three most common wasp species belonging to the family Vespidae for
chitin extraction and characterization. Chitin was isolated from each wasp
species and characterized by Fourier transform infrared spectroscopy (FTIR),
thermogravimetric analysis (TGA), X-ray diffractometry (XRD), elemental analysis
(EA), and scanning electron microscopy (SEM). The chitin contents of Vespa
crabro, Vespa orientalis, and Vespula germanica were 8.3, 6.4, and 11.9%,
respectively. The crystalline index (CrI) values for the chitin extracted from
each species were 69.88, 53.92, and 50%, respectively. The most important finding
of the study is that although the same method was used to extract chitin from
each of the three wasp species, the degree of acetylation was different: for V.
crabro and V. orientalis it was 96.85 and 99.82% (the chitin was extremely pure),
respectively, whereas that for V. germanica the chitin was 79.83%.
PMID- 25850819
TI - Nonsuicidal self-injury and affect regulation: recent findings from experimental
and ecological momentary assessment studies and future directions.
AB - CONTEXT: Although research indicates that nonsuicidal self-injury (NSSI) may be
used as a form of emotion regulation, studies have largely relied on the use of
retrospective self-report data, which limits inferences about directionality of
effects. Recently, researchers have started to employ lab-based experimental
(e.g., guided imagery, acute pain) and moment sampling approaches to the study of
NSSI. METHODS: In the present study, we conducted a review of this recent
literature, using several electronic databases (e.g., PsychINFO, ERIC, CINAHL).
RESULTS: We identified 18 studies that met our inclusion criteria. Findings
indicated that the administration of pain was associated with decreases in
negative affect among both self-injurers and noninjurers, although these declines
were more pronounced for self-injurers in some studies. CONCLUSIONS: We discuss
findings within the context of two central theories (i.e., opponent-process
theory and distraction theory) and offer several recommendations for future
research in this area.
PMID- 25850820
TI - Ischemia and reperfusion related myocardial inflammation: A network of cells and
mediators targeting the cardiomyocyte.
AB - Occlusion of a coronary artery if maintained for longer period of time results in
damage of the cardiac tissue. However, restoration of blood flow to previously
ischemic tissue can itself induce further cardiac damage, a phenomenon known as
myocardial reperfusion injury. Cardiac homoeostasis is supported by a network of
direct and indirect interactions between cardiomyocytes and resident cell types
such as fibroblasts, adipocytes, and endothelial cells or invading blood cells.
This review will discuss the role of the cellular interplay in ischemia
reperfusion injury from a cardiomyocyte-centered view, although we are aware that
other cellular interactions are equally important. We will try to work out
currently unresolved questions and potential future directions in the field.
PMID- 25850823
TI - Development of full-thickness human skin equivalents with blood and lymph-like
capillary networks by cell coating technology.
AB - We developed a human skin equivalent (HSE) containing blood and lymph-like
capillary networks using a cell coating technique, which is a rapid fabrication
technology of three-dimensional cellular constructs by cell surface coating using
layer-by-layer assembled nanofilms of extracellular matrices. The thickness of
dermis consisting of normal human dermal fibroblasts was easily controlled from
approximately 5 to 100 um by altering the seeded cell number. Keratinocytes as a
major cell population showed homogeneous differentiation on the surface of the
dermis by lifting to air-liquid interface. Histological analysis revealed four
distinct layers such as basal layer, spinous layer, granular layer, and cornified
cell layer in the epidermis. Interestingly, the measurement of transepithelial
electrical resistance (TEER) indicated prolongation of the attainment time for
maximum value by increasing the number of the dermal fibroblasts, and the HSEs
with six layers of dermis revealed the longest period maintaining over 500 Omega
cm(2) of TEER. The co-sandwich culture of human umbilical vein endothelial cells
and normal human dermal lymphatic microvascular endothelial cells within eight
layered dermis showed in vitro co-network formation of individual blood and lymph
like capillaries inside the dermis. This is the report for homogeneous full
thickness HSEs with blood and lymph capillary networks, which will be useful for
biomedical and pharmaceutical applications.
PMID- 25850822
TI - Online monitoring of fermentation processes via non-invasive low-field NMR.
AB - For the development of biotechnological processes in academia as well as in
industry new techniques are required which enable online monitoring for process
characterization and control. Nuclear magnetic resonance (NMR) spectroscopy is a
promising analytical tool, which has already found broad applications in offline
process analysis. The use of online monitoring, however, is oftentimes
constrained by high complexity of custom-made NMR bioreactors and considerable
costs for high-field NMR instruments (>US$200,000). Therefore, low-field (1) H
NMR was investigated in this study in a bypass system for real-time observation
of fermentation processes. The new technique was validated with two microbial
systems. For the yeast Hansenula polymorpha glycerol consumption could accurately
be assessed in spite of the presence of high amounts of complex constituents in
the medium. During cultivation of the fungal strain Ustilago maydis, which is
accompanied by the formation of several by-products, the concentrations of
glucose, itaconic acid, and the relative amount of glycolipids could be
quantified. While low-field spectra are characterized by reduced spectral
resolution compared to high-field NMR, the compact design combined with the high
temporal resolution (15 s-8 min) of spectra acquisition allowed online monitoring
of the respective processes. Both applications clearly demonstrate that the
investigated technique is well suited for reaction monitoring in opaque media
while at the same time it is highly robust and chemically specific. It can thus
be concluded that low-field NMR spectroscopy has a great potential for non
invasive online monitoring of biotechnological processes at the research and
practical industrial scales.
PMID- 25850824
TI - VARIABILITY IN THE ULTRASONOGRAPHIC APPEARANCE OF THE PANCREAS IN HEALTHY DOGS
COMPARED TO DOGS WITH HYPERADRENOCORTICISM.
AB - Anecdotally, an unusually hyperechoic pancreas can be found in seemingly healthy
dogs on ultrasound examination and the prevalence and clinical significance of
this finding is unknown. The objective of this study was to describe the
prevalence of a hyperechoic and/or heterogenous pancreas in healthy dogs and
correlate these findings to weight, age, and body condition score (BCS). An
additional objective was to describe the prevalence of a hyperechoic and/or
heterogenous pancreas in dogs with hyperadrenocorticism and compare this to the
healthy dogs. Pancreata of 74 healthy dogs were evaluated prospectively and
pancreatic echogenicity and echotexture were graded. Each dog's age, BCS, and
weight were recorded. Dogs were screened for health by physical examination,
serum chemistry panel, urine specific gravity, and a canine pancreatic lipase
immunoreactivity assay. Pancreatic images for 92 dogs having hyperadrenocorticism
were also reviewed and pancreatic echogenicity and echotexture were recorded. The
prevalence of pancreatic hyperechogenicity in normal dogs was 7% (5 of 74) and
heterogeneity was 40% (30 of 74). No correlation existed between pancreatic
echogenicity and weight, age, or BCS (P > 0.1 for all sets). A statistically
significant increase in the proportion of dogs having a hyperechoic pancreas was
found in the hyperadrenocorticism sample of dogs (40%, 37 of 92, P < 0.0001). The
underlying cause of pancreatic variability in the few healthy dogs and in dogs
with hyperadrenocorticism is unknown and the varying appearance of the pancreas
in these samples confounds interpretation of diseases such as chronic
pancreatitis.
PMID- 25850821
TI - Toward a Cancer Drug of Fungal Origin.
AB - Although fungi produce highly structurally diverse metabolites, many of which
have served as excellent sources of pharmaceuticals, no fungi-derived agent has
been approved as a cancer drug so far. This is despite a tremendous amount of
research being aimed at the identification of fungal metabolites with promising
anticancer activities. This review discusses the results of clinical testing of
fungal metabolites and their synthetic derivatives, with the goal to evaluate how
far we are from an approved cancer drug of fungal origin. Also, because in vivo
studies in animal models are predictive of the efficacy and toxicity of a given
compound in a clinical situation, literature describing animal cancer testing of
compounds of fungal origin is reviewed as well. Agents showing the potential to
advance to clinical trials are also identified. Finally, the technological
challenges involved in the exploitation of fungal biodiversity and procurement of
sufficient quantities of clinical candidates are discussed, and potential
solutions that could be pursued by researchers are highlighted.
PMID- 25850825
TI - In situ ultrasound imaging of silk hydrogel degradation and neovascularization.
AB - Ultrasound (US) is a useful technique to monitor morphological and functional
changes of biomaterial implants without sacrificing the animal. Contrast-enhanced
ultrasound (CEUS) along with two-dimensional (2D) US were used to characterize
the biodegradation and neovascularization of silk protein (8 wt%) hydrogel
implants in rats. Cylinder-shaped silk hydrogel plugs were implanted into the
space between the hind limb thigh muscles in Wistar rats (n = 6). The increase of
echogenicity in 2D US revealed tissue-ingrowth-accompanied gel degradation over
18 weeks. The shape and size of the implanted gels remained qualitatively
unchanged until week 15, as confirmed by Bland and Altman analysis and
visualization of retrieved samples. Using CEUS, neovascularization was monitored
by the presence of microbubbles in the gel area, and the dynamic vascularization
process was indicated by the contrast enhancement values, which showed a
relatively low level (< 5 dB) during weeks 1-8 and significantly increased levels
(around 20 dB at week 15 and > 35 dB at week 18), suggesting that major
vascularization had occurred in the gel implants by this time point. Histological
and scanning electron microscopic analysis of explants revealed time-dependent
increases in the pore size of the gel matrix, the presence of endothelial and red
blood cells and the number of blood vessels in the gel implants, indicating that
degradation and vascularization did occur in silk gel implants during the time
period. The present study demonstrates the use of US imaging for monitoring of in
vivo degradation and vascularization of silk implants in a non-destructive way.
Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 25850826
TI - Incidence and severity of reported acute sports injuries in 35 sports using
insurance registry data.
AB - Acute injuries in sport are still a problem where limited knowledge of incidence
and severity in different sports at national level exists. In Sweden, 80% of the
sports federations have their mandatory injury insurance for all athletes in the
same insurance company and injury data are systematically kept in a national
database. The aim of the study was to identify high-risk sports with respect to
incidence of acute and severe injuries in 35 sports reported to the database. The
number and incidences of injuries as well as injuries leading to permanent
medical impairment (PMI) were calculated during 2008-2011. Each year
approximately 12,000 injuries and 1,162,660 licensed athletes were eligible for
analysis. Eighty-five percent of the injuries were reported in football, ice
hockey, floorball, and handball. The highest injury incidence as well as PMI was
in motorcycle, handball, skating, and ice hockey. Females had higher risk of a
PMI compared with males in automobile sport, handball, floorball, and football.
High-risk sports with numerous injuries and high incidence of PMI injuries were
motorcycle, handball, ice hockey, football, floorball, and automobile sports.
Thus, these sports ought to be the target of preventive actions at national
level.
PMID- 25850827
TI - Cochrane reviewers' response to Alper and colleagues' analysis of thrombolysis in
acute ischaemic stroke.
PMID- 25850828
TI - Betatrophin levels are increased in women with gestational diabetes mellitus
compared to healthy pregnant controls.
AB - OBJECTIVE: Betatrophin has recently been introduced as a novel
adipokine/hepatokine, which promotes pancreatic beta cell proliferation and
improves glucose tolerance in several mouse models of insulin resistance.
However, regulation of betatrophin in gestational diabetes mellitus (GDM), as
well as its association with markers of obesity, such as glucose and lipid
metabolism, inflammation, and renal function, have not been elucidated. DESIGN
AND METHODS: Circulating betatrophin was quantified in 74 women with GDM and 74
healthy and gestational age-matched controls by ELISA. In a subset of the study
population comprising of 85 patients (41 previous controls, 44 previous women
with GDM), postpartum betatrophin levels were measured in a follow-up study.
RESULTS: Median (interquartile range) serum betatrophin levels were higher in
women with GDM (1.79 (0.53) MUg/l) as compared to non-diabetic pregnant controls
(1.58 (0.44) MUg/l) (P=0.002). In multivariate analysis, GDM status was an
independent and positive predictor of circulating betatrophin (P=0.001).
Furthermore, betatrophin levels were significantly higher during gestation (1.70
(0.53) MUg/l) as compared to postpartum levels (1.55 (0.66) MUg/l) (P=0.028).
Moreover, postpartum irisin remained a positive and independent predictor of
postpartum betatrophin concentrations. CONCLUSIONS: Women with GDM have
significantly higher betatrophin levels as compared to healthy pregnant controls
and GDM status positively predicts circulating betatrophin. Furthermore,
postpartum levels are significantly lower as compared to betatrophin
concentrations during pregnancy. Moreover, irisin is a significant predictor of
postpartum betatrophin levels.
PMID- 25850829
TI - Novel inflammatory biomarkers in primary hyperparathyroidism.
AB - OBJECTIVE: Primary hyperparathyroidism (PHPT) has been associated with low-grade
inflammation and increased risk of cardiovascular disease (CVD). The aim of the
study was to investigate systemic levels of pro-inflammatory proteins that
previously have not been examined in patients with PHPT. The selection of the pro
inflammatory biomarkers included in this study, MMP9, S100A4, S100A8/A9 and the
receptors sCD14 and RAGE, was based on a previous microarray screen of mRNAs in
adipose tissue from PHPT patients. DESIGN: A prospective study was conducted on a
total of 57 patients with PHPT and a control group of 20 healthy blood donors.
METHODS: PHPT patients with normalisation of serum calcium levels after
parathyroidectomy were followed for 6 months. Forty-two patients participated in
the longitudinal study, in which blood samples were taken at inclusion, and 1, 3
and 6 months after surgery. RESULTS: We observed increased serum levels of MMP9
(P=0.029), S100A4 (P<0.001) and sCD14 (P=0.002) in the 57 patients with PHPT
compared to the control-group. During 6 months of follow up, S100A4 (P=0.022) and
sCD14 (0.002) decreased significantly, while serum levels of MMP9 increased
(P=0.025). CONCLUSIONS: The results demonstrate an increased inflammatory
response in PHPT patients shown by elevated MMP9, S100A4 and sCD14 at inclusion.
During the 6 months of follow-up, MMP9 increased further, possibly due to the
tissue repair process after parathyroidectomy. S100A4 and sCD14 decreased after
surgery demonstrating a partial reversal of the systemic inflammation.
PMID- 25850830
TI - O2 sensing dynamics of BiFeO3 nanofibers: effect of minor carrier compensation.
AB - In this paper we investigate O(2) sensing dynamics in BiFeO(3) (BFO) nanofibers
at various concentrations and temperatures, by using a combined experiment and
computer simulation approach. Samples of pristine BFO, Ni-doped BFO, and Pb-doped
BFO nanofibers were prepared. By incorporating Ni and Pb, additional acceptor
states are introduced in BFO. Density functional theory calculations show that Ni
prefers to substitute Fe site while Pb substitutes Bi site, resulting in a new
deep donor originating from Ni interstitial defects, along with oxygen vacancies
(V(o)). We find that both the sensing response and recovery time are shorter in
samples made of pristine BFO nanofibers than in Ni- and Pb-doped nanofiber
samples. We interpret the observed sensing dynamics through charge transport
theory of the major (acceptors) and minor (donors) carriers, and found that the
minor carrier compensation plays a significant role in determining the response
and recovery time of the sensor device. This minor carrier compensation charge
transport mechanism will provide new insights into more robust sensor development
strategies, and into the research of ion-electron coupling in chemical dynamics
of semiconductors.
PMID- 25850832
TI - Endoscopic ultrasound-guided fine needle aspiration is highly accurate for the
diagnosis of perirectal recurrence of colorectal cancer.
AB - BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration is highly
accurate for the diagnosis of malignancies surrounding the gastrointestinal
tract. There is a lack of information on the usefulness of this technique in the
diagnosis of colorectal cancer recurrence. OBJECTIVE: The purpose of this work
was to investigate the performance characteristics of endoscopic ultrasound
guided fine needle aspiration for the cytologic diagnosis of perirectal
recurrence of colorectal cancer. DESIGN: This was a retrospective study on the
clinical and radiologic suspicion of perirectal recurrence of colorectal cancer.
SETTINGS: The study was conducted at 4 tertiary hospitals. PATIENTS: Consecutive
patients with suspicion of perirectal recurrence of colorectal cancer undergoing
endoscopic ultrasound-guided fine needle aspiration between 2000 and 2013 were
included in this study. INTERVENTIONS: The study intervention was endoscopic
ultrasound-guided fine needle aspiration. MAIN OUTCOME MEASURES: Endoscopic
ultrasound-guided fine needle aspiration performance characteristics and outcome
(malignant or benign) were analyzed. The gold standard was cytologic results if
malignancy or follow-up if benignity. RESULTS: A total of 58 patients were
included (32 men; mean age, 64.2 +/- 10.0 years [range, 44-88 years]). The
location of the initial neoplasm was the rectum for 42 patients and the colon for
16 patients. Endoscopic ultrasound findings included a mass in the anastomosis (n
= 8), perirectal fat (n = 23), lymph nodes (n = 20), or asymmetric thickness of
the rectal wall (n = 6). Cytology showed malignancy in 38 patients (67%), benign
features in 17 (30%), and was not evaluable in 2. Mean follow-up to confirm a
benign outcome was 51.3 +/- 30.3 months (range, 5.2-180.0 months). Final outcome
was recurrence in 40 patients (69%) and benignity in 18 patients (31%).
Performance characteristics of endoscopic ultrasound-guided fine needle
aspiration were sensitivity (97%), specificity (100%), positive predictive value
(100%), negative predictive value (94%), and accuracy (98%). In the intention to
diagnose analysis, the corresponding values were 95%, 100%, 100%, 90%, and 96%.
LIMITATIONS: This was a retrospective series with a limited number of patients.
CONCLUSIONS: Endoscopic ultrasound-guided fine needle aspiration is a highly
accurate tool for the cytologic diagnosis of perirectal recurrence in patients
with previous colorectal cancer.
PMID- 25850831
TI - DOF AFFECTING GERMINATION 2 is a positive regulator of light-mediated seed
germination and is repressed by DOF AFFECTING GERMINATION 1.
AB - BACKGROUND: The transcription factor DOF AFFECTING GERMINATION1 (DAG1) is a
repressor of the light-mediated seed germination process. DAG1 acts downstream
PHYTOCHROME INTERACTING FACTOR3-LIKE 5 (PIL5), the master repressor, and
negatively regulates gibberellin biosynthesis by directly repressing the
biosynthetic gene AtGA3ox1. The Dof protein DOF AFFECTING GERMINATION (DAG2)
shares a high degree of aminoacidic identity with DAG1. While DAG1 inactivation
considerably increases the germination capability of seeds, the dag2 mutant has
seeds with a germination potential substantially lower than the wild-type,
indicating that these factors may play opposite roles in seed germination.
RESULTS: We show here that DAG2 expression is positively regulated by
environmental factors triggering germination, whereas its expression is repressed
by PIL5 and DAG1; by Chromatin Immuno Precipitation (ChIP) analysis we prove that
DAG1 directly regulates DAG2. In addition, we show that Red light significantly
reduces germination of dag2 mutant seeds. CONCLUSIONS: In agreement with the seed
germination phenotype of the dag2 mutant previously published, the present data
prove that DAG2 is a positive regulator of the light-mediated seed germination
process, and particularly reveal that this protein plays its main role downstream
of PIL5 and DAG1 in the phytochrome B (phyB)-mediated pathway.
PMID- 25850833
TI - Adenocarcinoma of the rectum in patients under age 40 is increasing: impact of
signet-ring cell histology.
AB - BACKGROUND: Overall, the incidence of colorectal cancer appears to be stable or
diminishing. However, based on our practice pattern, we observed that the
incidence of rectal cancer in patients under 40 is increasing and may be
associated with a prominence of signet-ring cell histology. OBJECTIVE: The aim of
this study was to verify the rising trend in rectal cancer in patients under 40
and describe the histology prominent in that cohort. DESIGN: This is a
retrospective cohort study. SETTING AND PATIENTS: We performed a retrospective
cohort study of all patients diagnosed with rectal adenocarcinoma from 1980 to
2010 using the Surveillance, Epidemiology, and End Results cancer registry. MAIN
OUTCOME MEASURES: Rectal cancer incidence, histology, and associated staging
characteristics were the primary outcomes measured. RESULTS: Although the
incidence of rectal cancer for all ages remained stable from 1980 to 2010, we
observed an annual percent change of +3.6% in the incidence of rectal cancer in
patients under 40. The prevalence of signet cell histology in patients under 40
was significantly greater than in patients over 40 (3% vs 0.87%, p < 0.01). A
multivariate regression analysis revealed an adjusted odds ratio of 3.6 (95% CI,
2.6-5.1) for signet cell histology in rectal adenocarcinoma under age 40. Signet
cell histology was also significantly associated with a more advanced stage at
presentation, poorly differentiated tumor grade, and worse prognosis compared
with mucinous and nonmucinous rectal adenocarcinoma. LIMITATIONS: The study was
limited by its retrospective nature and the information available in the
Surveillance, Epidemiology, and End Results database. CONCLUSIONS: Despite a
stable incidence of rectal cancer for all ages, the incidence in patients under
40 has quadrupled since 1980, and cancers in this group are 3.6 times more likely
to have signet cell histology. Given the worse outcomes associated with signet
cell histology, these data highlight a need for thorough evaluation of young
patients with rectal symptoms.
PMID- 25850834
TI - Feasibility of modified short-course radiotherapy combined with a
chemoradiosensitizer for T3 rectal cancer.
AB - BACKGROUND: 5-Fluorouracil-based chemotherapy is considered to be a
radiosensitizer; however, conventional short-course radiotherapy combined with
chemotherapy is generally thought to not be feasible because of the prevalence of
side effects. OBJECTIVE: The aim of this study was to evaluate the feasibility of
modified short-course radiotherapy combined with a chemoradiosensitizer for T3
rectal cancer. DESIGN AND SETTINGS: This study was retrospective in nature and
used a prospectively collected database. PATIENTS: Patients with T3 rectal cancer
located below the peritoneum reflection were selected. INTERVENTIONS: A total
dose of 25 Gy of radiotherapy was administered in 10 fractions of 2.5 Gy each for
5 days. Radiotherapy was performed with S-1 as a radiosensitizer from day 1 to
day 10. Surgery was targeted to be performed 4 weeks after radiotherapy. MAIN
OUTCOME MEASUREMENTS: The morbidity, sphincter-preserving rate, anal function,
and long-term outcomes were assessed. RESULTS: All patients (n = 170) completed
the radiotherapy regimen and 166 (97.6%) completed the combination regimen with
chemotherapy. A total of 149 patients (87.6%) had sphincter-preserving surgery
(double stapling technique (DST), 58 patients; intersphincteric resection (ISR),
91 patients), and postoperative complications were relatively mild (anastomotic
leakage, 15.4%; intra-abdominal infection, 8.2%). Among those undergoing
sphincter preserving surgery, the 5-year local relapse-free survival rate was
94.3% in the DST group, and 89.8% in the ISR group. With respect to the anal
function, the Wexner score the first year after stoma closure for the double
stapling technique group was 6 and that for intersphincteric resection was 15;
however, the score for the intersphincteric resection group was improved to 8 at
4 years after stoma closure. LIMITATIONS: This study had limitations because it
was an uncontrolled, 1-arm, retrospective review with a small sample size.
CONCLUSIONS: Modified short-course radiotherapy combined with
chemoradiosensitizer is a feasible approach for treating T3 rectal cancer. With
the use of the short-course approach, efforts to reduce the incidence of side
effects by appropriately prolonging the waiting period enable the administration
of combination treatment with short-course radiotherapy and chemotherapy.
PMID- 25850835
TI - IPAA-related sepsis significantly increases morbidity of ileoanal pouch excision.
AB - BACKGROUND: Perineal wound complications after ileoanal pouch excision remain a
significant cause of morbidity. OBJECTIVE: The purpose of this work was to
describe the incidence, outcomes, and predictors of perineal wound complications
after pouch excision. DESIGN: This was a retrospective medical chart review.
SETTINGS: The study was conducted in a single clinical institution. PATIENTS:
Patients who underwent pouch excision at our institution from July 1992 through
July 2012 were identified. Patient and perioperative variables were reviewed.
Multivariate and univariate analyses were undertaken. MAIN OUTCOME MEASURES:
Perineal wound (including perineal wound infection and persistent perineal sinus
[nonhealing by 6 months]) and perineal hernia were measured. RESULTS: A total of
47 patients (mean age, 46 years; 42.6% men) with familial adenomatous polyposis
(10.6%), mucosal ulcerative colitis (61.7%), or Crohn's disease (27.7%) underwent
pouch excision, including 36.2% for IPAA-related sepsis (presacral abscess;
perineal-, sacral-, or pouch-vaginal fistula; and anastomotic defect), 44.7% for
pouch dysfunction, 10.6% for refractory pouchitis, and 8.5% for neoplasia.
Fourteen (29.8%) developed perineal wound complications, including 100% perineal
wound infection, 28.6% persistent perineal sinus, and 7.1% perineal hernia.
Perineal wound infection was associated with delayed healing (>6 weeks; 71.4% vs
24.2%; p = 0.002) and IPAA-related sepsis (28.6% vs 0%; p = 0.001). Patients with
and without perineal wound complications were similar in age, diagnoses, fecal
diversion, immunosuppression, comorbid conditions, nutrition, and surgical
variables. Most patients underwent intersphincteric dissection (87.2%) with
primary perineal closure (97.0%). Perineal wound complications were significantly
associated with IPAA-related sepsis as an indication for pouch excision (57.1% vs
27.2%; p = 0.05), intraoperative pouch perforation (35.7% vs 9.1%, p =0.03), and
smoking (21.4% vs 3.0%; p = 0.04). IPAA-related sepsis and a current smoking
status (OR, 19.3 [95% CI, 1.8 -488.1]) are significant independent predictors on
multivariate logistic regression (OR, 6.4 [95% CI, 1.4-30.2]) of perineal wound
complications. All of the patients with persistent perineal sinus achieved
successful healing at a median of 734 days (range, 363-2182 days), requiring a
median of 1.5 procedures. LIMITATIONS: This was a single-center retrospective
review with a small sample size. CONCLUSIONS: Preoperative IPAA-related sepsis
and current smoking are significant risk factors for perineal wound complications
after pouch excision.
PMID- 25850836
TI - Relationship between model for end-stage liver disease score and 30-day outcomes
for patients undergoing elective colorectal resections: an American college of
surgeons-national surgical quality improvement program study.
AB - BACKGROUND: Patients with liver disease face significant risk of complications
and death when considering elective colorectal resection for benign or malignant
indications. OBJECTIVE: We sought to determine the relationship between Model of
End-Stage Liver Disease score and 30-day outcomes in patients undergoing elective
colorectal resections. DESIGN: This was a retrospective cohort study. SETTINGS:
The study included hospitals participating in the National Surgical Quality
Improvement Program. PATIENTS: Adult patients who underwent elective colorectal
resection from 2005 to 2011 were identified from the National Surgical Quality
Improvement Program database. Patients missing laboratory values necessary to
calculate the Model of End-Stage Liver Disease score were excluded (61% of 81,346
patients identified). MAIN OUTCOME MEASURES: Differences in patient- and disease
related characteristics by Model of End-Stage Liver Disease categories were
assessed with chi analyses. Thirty-day mortality and major morbidity were
examined using logistic regression. RESULTS: Of 31,950 patients undergoing
elective colorectal resections (14% including proctectomy), most (60%) were
performed for colon or rectal cancer; other benign indications included
diverticulitis (20%), polyp (10%), and IBD (10%). A total of 58% of patients had
a Model of End-Stage Liver Disease score of >=7. Increasing scores were
associated with older age; higher BMI; higher ASA class; lower albumin level; and
higher incidence of diabetes mellitus, pulmonary and cardiac disease,
hypertension, and dependent functional status. In univariate analysis, patients
with higher scores had a greater risk of 30-day mortality (score = 6 (0.69%); 7
11 (1.62%); 11-15 (4.52%); >15, (5.01%); p < 0.0001). After controlling for other
comorbidities, Model of End-Stage Liver Disease score remained a significant
predictor of 30-day mortality, major complications, and respiratory
complications. LIMITATIONS: This was a retrospective analysis of administrative
data, limiting some access to clinically relevant data. CONCLUSIONS: Consistent
with previous reports, patients with higher Model of End-Stage Liver Disease
scores have a significantly higher risk of death and major morbidity in the 30
days after elective colorectal resection (see Video, Supplemental Digital
Content, http://links.lww.com/DCR/A180).
PMID- 25850837
TI - What are the results of colonic volvulus surgery?
AB - BACKGROUND: Operative results of volvulus are largely unknown because of
infrequent diagnosis. OBJECTIVE: We examined the results of operative
intervention for colonic volvulus. DESIGN: We merged trackable data from the
California Inpatient Database with Supplemental Files for Revisit Analyses
between January 1, 2005, and December 31, 2007. SETTINGS: Trackable data from
California discharge records. PATIENTS: We identified all of the patients with
colonic volvulus who underwent 1 of 4 surgical procedures, including
manipulation/fixation of the colon, right colectomy, left colectomy, or total
colectomy. MAIN OUTCOME MEASURES: During the 36-month study period, we identified
recurrence risk, recurrence requiring reoperation, time to reoperation, stoma
formation, disposition on discharge, and in-hospital mortality. Fisher exact,
chi(2), and ANOVA tests were used when appropriate. RESULTS: We identified 2141
patients with colonic volvulus who were undergoing intraoperative
manipulation/fixation of the colon (n = 209 (12%)), right (n = 728 (41%)), left
(n = 781 (44%)), or total colectomy (n = 56 (3%)). Patients treated with
intraoperative manipulation/fixation were younger, more likely to be women, and
more likely to have private insurance. Patients who underwent total colectomy had
the highest risk of mortality (21%), highest risk of stoma creation (64%), and
longest length of stay (18 days); were more likely to be readmitted (9%); and
were the most likely to be discharged to a skilled nursing facility (48%).
Patients treated with intraoperative manipulation/fixation had the lowest
mortality, risk of stoma formation, length of stay, and likelihood of discharge
to skilled nursing facility but the highest risk of subsequent procedures for
volvulus (26%) over a follow-up ranging from 0 to 687 days. LIMITATIONS: This
study was limited by retrospective study design, heterogeneous patient factors,
and inability to identify the time of last follow-up. CONCLUSIONS: The majority
of patients with volvulus underwent a resectional procedure. A subset without
resection had favorable initial outcomes but remained at high risk for subsequent
procedures. There may be a potential role for evaluating intraoperative
manipulation/fixation in a small subset of patients with colonic volvulus.
PMID- 25850838
TI - Dynamic article: composite antropyloric valve and gracilis muscle transposition
for total anorectal reconstruction: a preliminary report.
AB - BACKGROUND: Technique and functional outcomes of anorectal reconstruction using
an antropyloric graft have been reported previously. This technique had
reasonable initial outcomes but lacked voluntary function. OBJECTIVE: We hereby
report the initial results of patients who underwent gracilis muscle wrapping
around the perineally transposed antropyloric valve in an attempt to improve
voluntary fecal control. SETTING: This study was conducted at a single tertiary
care institution. PATIENTS: Eight adult patients (7 men and 1 woman) with a
median age of 38 years (range, 19-51 years) underwent this procedure. Seven
patients already had anorectal reconstruction with a transposed antropyloric
valve, and 1 patient with severely damaged anal sphincter complex underwent
single-stage composite antropylorus transposition with a gracilis muscle wrap.
MAIN OUTCOME MEASURES: The primary outcome measures were anatomical integrity and
functional status of the composite graft in the perineum. RESULTS: No operative
mortality or serious procedure-related morbidity occurred in any patient. The
median postoperative resting pressure was 29 mmHg (range, 22-38 mmHg) and squeeze
pressure was 72.5 mmHg (range, 45-267 mmHg). There was a significant improvement
in the squeeze pressure following surgery (p = 0.039). Also, the St. Mark's
incontinence scores significantly improved in all patients and varied between 7
and 9 (p = 0.003). The ability to defer defecation and the reduced frequency of
leakage accidents were the prime reasons for improved postgraciloplasty outcomes
in these patients. On personal interviews, all patients who underwent this
procedure were satisfied with the results of their surgery. LIMITATIONS: A longer
follow-up with a larger sample size is required. Quality-of-life data have not
been evaluated in this study. CONCLUSIONS: Gracilis muscle wrapping around a
perineally transposed antropyloric valve is possible and improves the voluntary
control and overall functional outcomes in a select group of patients with end
stage fecal incontinence requiring anal replacement (Supplemental Digital Content
1, http://links.lww.com/DCR/A173).
PMID- 25850839
TI - Functional and histological evidence for the targeted therapy using biocompatible
polycaprolactone beads and autologous myoblasts in a dog model of fecal
incontinence.
AB - BACKGROUND: Injection of bulking agents into the anal canal is limited by several
factors, including biological resorption, particle migration, and ongoing
degradation of the injected bulking agent. OBJECTIVE: We investigated whether an
injection of polycaprolactone beads containing autologous myoblasts could improve
sphincter function in a dog model of fecal incontinence. DESIGN: The control sham
surgery group underwent skin incision around the anal sphincter (n = 5). Fecal
incontinence was induced by resecting 25% of the posterior internal/external anal
sphincter in another 10 dogs. After 1 month of sphincter injury, dogs were then
treated with (n = 5) or without (n = 5) polycaprolactone beads containing PKH-26
labeled autologous myoblasts. SETTING: This study was conducted at the department
of surgery in collaboration with the department of advanced materials. OUTCOME
MEASURES: Three months after injection treatment, the resting and contractile
pressure differences of the anal sphincter were compared, and histopathological
studies were performed. RESULTS: The anal pressures in untreated dogs were
significantly lower than those in the sham surgery group (p < 0.05). The resting
and contractile pressure differences were higher in treated dogs than in
untreated dogs (resting pressure difference: 0.7 +/- 0.5 vs -0.6 +/- 0.8 mmHg;
coefficient of the difference in recovery rate, 0.38; 95% CI, 0.15-0.61, p =
0.001; contractile pressure difference: 1.1 +/- 4.2 vs -3.9 +/- 2.6 mmHg;
coefficient, 1.63; 95% CI, 0.55-2.71, p = 0.003). Immunofluorescent staining
confirmed that the myoblasts had differentiated and synthesized myosin heavy
chain, as observed in vitro. LIMITATIONS: This study was limited by the lack of
comparison of injecting beads containing autologous myoblasts with injecting
myoblasts alone. CONCLUSION: This study shows that an injection of
polycaprolactone beads containing autologous myoblasts may improve anal sphincter
function in an animal model of fecal incontinence.
PMID- 25850841
TI - Long-term follow-up after surgery for simple and complex cryptoglandular
fistulas: fecal incontinence and impact on quality of life.
AB - BACKGROUND: Surgical management of cryptoglandular fistulas is a challenge
because the consequences of anal surgery potentially include fecal incontinence
and impaired quality of life. OBJECTIVE: To assess factors associated with fecal
incontinence after surgery for simple and complex cryptoglandular fistulas and to
determine the impact of incontinence on quality of life. DESIGN: The design is
retrospective and cross-sectional. SETTINGS: This study was conducted at an
academic tertiary center and at a private center specializing in proctologic
surgery. PATIENTS: All patients who underwent preoperative endoanal ultrasound
for cryptoglandular fistula between 2002 and 2012. MAIN OUTCOME MEASURES: A
questionnaire was sent out in October 2013 to evaluate incontinence (Wexner
score) and its impact on quality of life (FIQL). Variables tested for association
were patient demographics, fistula type, number of incised abscesses (0, 1, >1),
number of fistulotomies (0, 1, >1) and number of sphincter-sparing procedures (0,
1, >1). RESULTS: Of the 141 patients participating, 116 (82%; 76 men, 40 women)
returned all the questionnaires. Median follow-up from the first perianal fistula
surgery was 7.8 years (range, 2.1-18.1 years). Thirty-nine patients (34%)
experienced incontinence. Surgical fistulotomy, multiple abscess drainages and a
high transsphincteric or suprasphincteric fistula tract were associated with
incontinence. As compared to simple fistula (Wexner score, 1.2 [SD, 2.1]),
incontinence was worse after surgery for complex fistula (Wexner score, 4.7 [SD,
6.2], p = 0.001), as were quality of life elements, including lifestyle (p =
0.030), depression (p = 0.077) and embarrassment (p < 0.001). LIMITATIONS: Mainly
retrospective design without a standardized treatment protocol. CONCLUSION:
Surgical fistulotomy is the strongest risk factor for fecal incontinence. The
severity of incontinence increases with the complexity of the fistula, negatively
influencing quality of life. Special attention should be paid to these patients
so as to mitigate symptoms later in life. A shift to sphincter-sparing procedures
appears warranted.
PMID- 25850842
TI - Potential problems with the public reporting of risk-adjusted surgical outcomes.
PMID- 25850843
TI - Outcome science.
PMID- 25850840
TI - Factors that influence minority use of high-volume hospitals for colorectal
cancer care.
AB - BACKGROUND: Previous studies suggest that minorities cluster in low-quality
hospitals despite living close to better performing hospitals. This may
contribute to persistent disparities in cancer outcomes. OBJECTIVE: The purpose
of this work was to examine how travel distance, insurance status, and
neighborhood socioeconomic factors influenced minority underuse of high-volume
hospitals for colorectal cancer. DESIGN: The study was a retrospective, cross
sectional, population-based study. SETTINGS: All hospitals in California from
1996 to 2006 were included. PATIENTS: Patients with colorectal cancer diagnosed
and treated in California between 1996 and 2006 were identified using California
Cancer Registry data. MAIN OUTCOME MEASURES: Multivariable logistic regression
models predicting high-volume hospital use were adjusted for age, sex, race,
stage, comorbidities, insurance status, and neighborhood socioeconomic factors.
RESULTS: A total of 79,231 patients treated in 417 hospitals were included in the
study. High-volume hospitals were independently associated with an 8% decrease in
the hazard of death compared with other settings. A lower proportion of
minorities used high-volume hospitals despite a higher proportion living nearby.
Although insurance status and socioeconomic factors were independently associated
with high-volume hospital use, only socioeconomic factors attenuated differences
in high-volume hospital use of black and Hispanic patients compared with white
patients. LIMITATIONS: The use of cross-sectional data and racial and ethnic
misclassifications were limitations in this study. CONCLUSIONS: Minority patients
do not use high-volume hospitals despite improved outcomes and geographic access.
Low socioeconomic status predicts low use of high-volume settings in select
minority groups. Our results provide a roadmap for developing interventions to
increase the use of and access to higher quality care and outcomes. Increasing
minority use of high-volume hospitals may require community outreach programs and
changes in physician referral practices.
PMID- 25850844
TI - Should agraffectomy always be recommended to treat chronic sequelae following
stapled anorectal procedures?
PMID- 25850845
TI - The authors reply.
PMID- 25850846
TI - Slaughtering sacred cows: long-term surveillance after ileal pouch-anal
anastomosis for ulcerative colitis and choice of anastomosis.
PMID- 25850847
TI - The authors reply.
PMID- 25850848
TI - Time to Rethink ELAPE?
PMID- 25850849
TI - Must we continue to look for excuses?
PMID- 25850850
TI - Prevention of anal cancer -- can we do better?
PMID- 25850851
TI - Variation in lynch syndrome.
PMID- 25850855
TI - Morphine potentiates LPS-induced autophagy initiation but inhibits autophagosomal
maturation through distinct TLR4-dependent and independent pathways.
AB - AIM: Opioids are the most prescribed analgesics for moderate and severe pain
management; however, chronic use impairs host innate immune response and
increases susceptibility to infection. Recently, autophagy has been shown to be
an innate defence mechanism against bacterial infection. The effect of autophagy
induced bacterial clearance following morphine treatment has not been previously
investigated. METHODS: Autophagosomes were visualized by confocal microscopy
following GFP-LC3 transfection and also by transmission electron microscopy. The
relative protein levels were analysed by Western blot. Macrophages were
transfected with GFP-mcherry-LC3 simultaneously to monitor autolysosome formation
and subsequent events that lead to degradation. RESULTS: Morphine treatment
potentiated LPS-induced vesicular translocation of GFP-LC3 with a concurrent
increase in LC3-II levels. In addition, morphine upregulated LPS-induced Beclin1
level, but downregulated Bcl-2 level. We further show that p38 MAP kinase
signalling is required for autophagy activation. In contrast, morphine inhibited
LPS-induced autophagosome maturation and autophagolysosomal fusion as indicated
by the failure to recruit LAMP1 into autophagosome and reduced degradation of
SQSTM1/p62 protein level. Morphine modulation of LPS-induced autophagosome
maturation visualized using co-localization of GFP-mcherry-LC3 was TLR4
independent, but mediated through MU opioid receptor signalling. Correspondingly,
morphine and LPS co-treatment significantly increased Streptococcus pneumoniae
load, when compared with LPS treatment alone. CONCLUSION: These observations
imply that although morphine treatment facilitates LPS-induced autophagy, it
inhibits autophagolysosomal fusion leading to decreased bacterial clearance and
increased bacterial load. These observations support the increased susceptibility
to infection and the prevalence of persistent infection in the drug abuse
population.
PMID- 25850857
TI - Reflections on impact issues.
PMID- 25850856
TI - Transcriptional profile of the human pathogenic fungus Paracoccidioides lutzii in
response to sulfamethoxazole.
AB - Paracoccidioidomycosis (PCM) is the most prevalent mycosis in Latin America and
is caused by a group of fungi within the Paracoccidioides genus. The disease may
present clinical and pathological manifestations ranging from asymptomatic
pneumonia pulmonary lesions, to disseminated forms involving multiple organs.
Sulfonamides were the first drugs used to treat PCM and are still used against
this fungal infection. Sulfa drugs are competitive antagonists of rho
aminobenzoic acid (PABA), a reaction catalyzed by dihydropteroate synthase
(DHPS). However, the molecular effects of sulfonamides against the
Paracoccidioides genus are unknown. The aim of this work was to investigate the
global mechanism of action of sulfamethoxazole on Paracoccidioides lutzii. Yeast
cells were grown on minimum medium in the presence or absence of sulfamethoxazole
to construct EST libraries. The representational difference analysis (RDA)
technique was used to identify up- and down-regulated P. lutzii genes after
treatment with sulfamethoxazole. Approximately six transcripts related to
mitochondrial function were differentially expressed. To confirm the RDA and
bioinformatics results, several relevant genes were studied with quantitative
real-time polymerase chain reaction (qRT-PCR) to evaluate their levels of
expression. To confirm the impact of sulfamethoxazole on mitochondria, we
measured the reduction of tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) by P. lutzii with or without exposure to the
drug. MTT assays reveal that sulfamethoxazole produces a marked dose-dependent
adverse effect on P. lutzii. The transcriptional activity of selected genes in
infected macrophages corroborated our in vitro results. The results indicated
that sulfamethoxazole acts in P. lutzii as a competitor for amino acid, nucleic
acids and folate cofactor biosynthesis, disrupting mitochondrial functions.
PMID- 25850858
TI - Women outperform men in remembering to remember.
AB - The study of gender differences in prospective memory (i.e., remembering to
remember) has received modest attention in the literature. The few reported
studies investigating either subjective or objective evaluations of prospective
memory have shown inconsistent data. In this study, we aimed to verify the
presence of gender differences during the performance of an objective prospective
memory test by considering the weight of specific variables such as length of
delay, type of response, and type of cue. We submitted a sample of 100 healthy
Italian participants (50 men and 50 women) to a test expressly developed to
assess prospective memory: The Memory for Intentions Screening Test. Women
performed better than men in remembering to do an event-based task (i.e.,
prompted by an external event) and when the task required a physical response
modality. We discuss the behavioural differences that emerged by considering the
possible role of sociological, biological, neuroanatomical, and methodological
variables.
PMID- 25850859
TI - Probability Elicitation Under Severe Time Pressure: A Rank-Based Method.
AB - Probability elicitation protocols are used to assess and incorporate subjective
probabilities in risk and decision analysis. While most of these protocols use
methods that have focused on the precision of the elicited probabilities, the
speed of the elicitation process has often been neglected. However, speed is also
important, particularly when experts need to examine a large number of events on
a recurrent basis. Furthermore, most existing elicitation methods are numerical
in nature, but there are various reasons why an expert would refuse to give such
precise ratio-scale estimates, even if highly numerate. This may occur, for
instance, when there is lack of sufficient hard evidence, when assessing very
uncertain events (such as emergent threats), or when dealing with politicized
topics (such as terrorism or disease outbreaks). In this article, we adopt an
ordinal ranking approach from multicriteria decision analysis to provide a fast
and nonnumerical probability elicitation process. Probabilities are subsequently
approximated from the ranking by an algorithm based on the principle of maximum
entropy, a rule compatible with the ordinal information provided by the expert.
The method can elicit probabilities for a wide range of different event types,
including new ways of eliciting probabilities for stochastically independent
events and low-probability events. We use a Monte Carlo simulation to test the
accuracy of the approximated probabilities and try the method in practice,
applying it to a real-world risk analysis recently conducted for DEFRA (the U.K.
Department for the Environment, Farming and Rural Affairs): the prioritization of
animal health threats.
PMID- 25850860
TI - The Plasmodium falciparum exportome contains non-canonical PEXEL/HT proteins.
AB - The pathogenicity of Plasmodium falciparum is partly due to parasite-induced host
cell modifications. These modifications are facilitated by exported P. falciparum
proteins, collectively referred to as the exportome. Export of several hundred
proteins is mediated by the PEXEL/HT, a protease cleavage site. The PEXEL/HT is
usually comprised of five amino acids, of which R at position 1, L at position 3
and E, D or Q at position 5 are conserved and important for export. Non-canonical
PEXEL/HTs with K or H at position 1 and/or I at position 3 are presently
considered non-functional. Here, we show that non-canonical PEXEL/HT proteins are
overrepresented in P. falciparum and other Plasmodium species. Furthermore, we
show that non-canonical PEXEL/HTs can be cleaved and can promote export in both a
REX3 and a GBP reporter, but not in a KAHRP reporter, indicating that non
canonical PEXEL/HTs are functional in concert with a supportive sequence
environment. We then selected P. falciparum proteins with a non-canonical
PEXEL/HT and show that some of these proteins are exported and that their export
depends on non-canonical PEXEL/HTs. We conclude that PEXEL/HT plasticity is
higher than appreciated and that non-canonical PEXEL/HT proteins cannot
categorically be excluded from Plasmodium exportome predictions.
PMID- 25850862
TI - Beyond molecules: mesoporous supramolecular frameworks self-assembled from
coordination cages and inorganic anions.
AB - Biological function arises by the assembly of individual biomolecular modules
into large aggregations or highly complex architectures. A similar strategy is
adopted in supramolecular chemistry to assemble complex and highly ordered
structures with advanced functions from simple components. Here we report a
series of diamond-like supramolecular frameworks featuring mesoporous cavities,
which are assembled from metal-imidazolate coordination cages and various anions.
Small components (metal ions, amines, aldehydes, and anions) are assembled into
the hierarchical complex structures through multiple interactions including
covalent bonds, dative bonds, and weak C-H???X (X=O, F, and pi) hydrogen bonds.
The mesoporous cavities are large enough to trap organic dye molecules,
coordination cages, and vitamin B12. The study is expected to inspire new types
of crystalline supramolecular framework materials based on coordination motifs
and inorganic ions.
PMID- 25850861
TI - Know your tools--concordance of different methods for measuring brain volume
change after ischemic stroke.
AB - INTRODUCTION: Longitudinal brain volume changes have been investigated in a
number of cerebral disorders as a surrogate marker of clinical outcome. In
stroke, unique methodological challenges are posed by dynamic structural changes
occurring after onset, particularly those relating to the infarct lesion. We
aimed to evaluate agreement between different analysis methods for the
measurement of post-stroke brain volume change, and to explore technical
challenges inherent to these methods. METHODS: Fifteen patients with anterior
circulation stroke underwent magnetic resonance imaging within 1 week of onset
and at 1 and 3 months. Whole-brain as well as grey- and white-matter volume were
estimated separately using both an intensity-based and a surface watershed-based
algorithm. In the case of the intensity-based algorithm, the analysis was also
performed with and without exclusion of the infarct lesion. Due to the effects of
peri-infarct edema at the baseline scan, longitudinal volume change was measured
as percentage change between the 1 and 3-month scans. Intra-class and concordance
correlation coefficients were used to assess agreement between the different
analysis methods. Reduced major axis regression was used to inspect the nature of
bias between measurements. RESULTS: Overall agreement between methods was modest
with strong disagreement between some techniques. Measurements were variably
impacted by procedures performed to account for infarct lesions. CONCLUSIONS:
Improvements in volumetric methods and consensus between methodologies employed
in different studies are necessary in order to increase the validity of
conclusions derived from post-stroke cerebral volumetric studies. Readers should
be aware of the potential impact of different methods on study conclusions.
PMID- 25850863
TI - The Use of Pediatric Ventricular Assist Devices in Children's Hospitals From 2000
to 2010: Morbidity, Mortality, and Hospital Charges.
AB - OBJECTIVE: The use of ventricular assist devices has increased dramatically in
adult heart failure patients. However, the overall use, outcome, comorbidities,
and resource utilization of ventricular assist devices in pediatric patients have
not been well described. We sought to demonstrate that the use of ventricular
assist devices in pediatric patients has increased over time and that mortality
has decreased. DESIGN: A retrospective study of the Pediatric Health Information
System database was performed for patients 20 years old or younger undergoing
ventricular assist device placement from 2000 to 2010. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Four hundred seventy-five pediatric patients were
implanted with ventricular assist devices during the study period: 69 in 2000
2003 (era 1), 135 in 2004-2006 (era 2), and 271 in 2007-2010 (era 3). Median age
at ventricular assist device implantation was 6.0 years (interquartile range, 0.5
13.8), and the proportion of children who were 1-12 years old increased from 29%
in era 1 to 47% in era 3 (p = 0.002). The majority of patients had a diagnosis of
cardiomyopathy; this increased from 52% in era 1 to 72% in era 3 (p = 0.003).
Comorbidities included arrhythmias (48%), pulmonary hypertension (16%), acute
renal failure (34%), cerebrovascular disease (28%), and sepsis/systemic
inflammatory response syndrome (34%). Two hundred forty-seven patients (52%)
underwent heart transplantation and 327 (69%) survived to hospital discharge.
Hospital mortality decreased from 42% in era 1 to 25% in era 3 (p = 0.004).
Median hospital length of stay increased (37 d [interquartile range, 12-64 d] in
era 1 vs 69 d [interquartile range, 35-130] in era 3; p < 0.001) and median
adjusted hospital charges increased ($630,630 [interquartile range, $227,052
$853,318] in era 1 vs $1,577,983 [interquartile range, $874,463-$2,280,435] in
era 3; p < 0.001). Factors associated with increased mortality include age less
than 1 year (odds ratio, 2.04; 95% CI, 1.01-3.83), acute renal failure (odds
ratio, 2.1; 95% CI, 1.26-3.65), cerebrovascular disease (odds ratio, 2.1; 95% CI,
1.25-3.62), and extracorporeal membrane oxygenation (odds ratio, 3.16; 95% CI,
1.79-5.60). Ventricular assist device placement in era 3 (odds ratio, 0.3; 95%
CI, 0.15-0.57) and a diagnosis of cardiomyopathy (odds ratio, 0.5; 95% CI, 0.32
0.84), were associated with decreased mortality. Large-volume centers had lower
mortality (odds ratio, 0.55; 95% CI, 0.34-0.88), lower use of extracorporeal
membrane oxygenation, and higher charges. CONCLUSIONS: The use of ventricular
assist devices and survival after ventricular assist device placement in
pediatric patients have increased over time, with a concomitant increase in
resource utilization. Age under 1 year, certain noncardiac morbidities, and the
use of extracorporeal membrane oxygenation are associated with worse outcomes.
Lower mortality was seen at larger volume ventricular assist device centers.
PMID- 25850864
TI - A Case-Control Study on the Impact of Ventilator-Associated Tracheobronchitis in
the PICU.
AB - OBJECTIVES: Hospital-acquired infections increase morbidity, mortality, and
charges in the PICU. We implemented a quality improvement bundle directed at
ventilator-associated pneumonia in our PICU in 2005. We observed an increase in
ventilator-associated tracheobronchitis coincident with the near-elimination of
ventilator-associated pneumonia. The impact of ventilator-associated
tracheobronchitis on critically ill children has not been previously described.
Accordingly, we hypothesized that ventilator-associated tracheobronchitisis
associated with increased length of stay, mortality, and hospital charge. DESIGN:
Retrospective case-control study. PATIENTS: Critically ill children admitted to a
quaternary PICU at a free-standing academic children's hospital in the United
States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a
retrospective case control study, with institutional review board approval, of 77
consecutive cases of ventilator-associated tracheobronchitis admitted to our PICU
from 2004-2010. We matched each case with a control based on the following
criteria (in rank order): age range (< 30 d, 30 d to 24 mo, 24 mo to 12 yr, > 12
yr), admission Pediatric Risk of Mortality III score +/- 10, number of ventilator
days of control group (> 75% of days until development of ventilator-associated
tracheobronchitis), primary diagnosis, underlying organ system dysfunction,
surgical procedure, and gender. The primary outcome measured was PICU length of
stay. Secondary outcomes included ventilator days, hospital length of stay,
mortality, and PICU and hospital charges. Data was analyzed using chi square
analysis and p less than 0.05 was considered significant. We successfully matched
45 of 77 ventilator-associated tracheobronchitis patients with controls. There
were no significant differences in age, gender, diagnosis, or Pediatric Risk of
Mortality III score between groups. Ventilator-associated tracheobronchitis
patients had a longer PICU length of stay (median, 21.5 d, interquartile range,
24 d) compared to controls (median, 18 d; interquartile range, 17 d), although
not statistically significant (p = 0.13). Ventilator days were also longer in the
ventilator-associated tracheobronchitis patients (median, 17 d; IQR, 22 d) versus
control (median, 10.5 d; interquartile range, 13 d) (p = 0.01). There was no
significant difference in total hospital length of stay (54 d vs 36 d; p = 0.69).
PICU mortality was higher in the ventilator-associated tracheobronchitis group
(15% vs 5%; p = 0.14), although not statistically significant. There was an
increase in both median PICU charges ($197,393 vs $172,344; p < 0.05) and
hospital charges ($421,576 vs $350,649; p < 0.05) for ventilator-associated
tracheobronchitis patients compared with controls. CONCLUSIONS: Ventilator
associated tracheobronchitis is a clinically significant hospital-acquired
infection in the PICU and is associated with longer duration of mechanical
ventilation and healthcare costs, possibly through causing a longer PICU length
of stay. Quality improvement efforts should be directed at reducing the incidence
of ventilator-associated tracheobronchitis in the PICU.
PMID- 25850865
TI - Tight Glycemic Control With Insulin Does Not Affect Skeletal Muscle Degradation
During the Early Postoperative Period Following Pediatric Cardiac Surgery.
AB - OBJECTIVE: Critical illness is associated with significant catabolism, and
persistent protein loss correlates with increased morbidity and mortality.
Insulin is a potent anticatabolic hormone; high-dose insulin decreases skeletal
muscle protein breakdown in critically ill pediatric surgical patients. However,
insulin's effect on protein catabolism when given at clinically utilized doses
has not been studied. The objective was to evaluate the effect of postoperative
tight glycemic control and clinically dosed insulin on skeletal muscle
degradation in children after cardiac surgery with cardiopulmonary bypass.
DESIGN: Secondary analysis of a two-center, prospective randomized trial
comparing tight glycemic control with standard care. Randomization was stratified
by study center. PATIENTS: Children 0-36 months who were admitted to the ICU
after cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: In the
tight glycemic control arm, insulin was titrated to maintain blood glucose
between 80 and 110 mg/dL. Patients in the control arm received standard care.
Skeletal muscle breakdown was quantified by a ratio of urinary 3-methylhistidine
to urinary creatinine. MEASUREMENTS AND MAIN RESULTS: A total of 561 patients
were included: 281 in the tight glycemic control arm and 280 receiving standard
care. There was no difference in 3-methylhistidine to creatinine between groups
(tight glycemic control, 249 +/- 127 vs standard care, 253 +/- 112, mean +/- SD
in MUmol/g; p = 0.72). In analyses restricted to the patients in tight glycemic
control arm, higher 3-methylhistidine to creatinine correlated with younger age,
as well as lower weight, weight-for-age z score, length, and body surface area (p
< 0.005 for each) and lower postoperative day 3 serum creatinine (r = -0.17; p =
0.02). Sex, prealbumin, and albumin were not associated with 3-methylhistidine to
creatinine. During urine collection, 245 patients (87%) received insulin.
However, any insulin exposure did not impact 3-methylhistidine to creatinine (t
test, p = 0.45), and there was no dose-dependent effect of insulin on 3
methylhistidine to creatinine (r = -0.03; p = 0.60). CONCLUSION: Although high
dose insulin has an anabolic effect in experimental conditions, at doses
necessary to achieve normoglycemia, insulin appears to have no discernible impact
on skeletal muscle degradation in critically ill pediatric cardiac surgical
patients.
PMID- 25850866
TI - Glucocorticoid Receptor Expression in Peripheral WBCs of Critically Ill Children.
AB - OBJECTIVES: To characterize glucocorticoid receptor expression in peripheral WBCs
of critically ill children using flow cytometry. DESIGN: Prospective
observational cohort. SETTING: A university-affiliated, tertiary PICU. PATIENTS:
Fifty-two critically ill children. INTERVENTIONS: Samples collected for
measurement of glucocorticoid receptor expression and parallel cortisol levels.
MEASUREMENTS AND MAIN RESULTS: Subjects with cardiovascular failure had
significantly lower glucocorticoid receptor expression both in CD4 lymphocytes
(mean fluorescence intensity, 522 [354-787] vs 830 [511-1,219]; p = 0.036) and
CD8 lymphocytes (mean fluorescence intensity, 686 [350-835] vs 946 [558-1,511]; p
= 0.019) compared with subjects without cardiovascular failure. Subjects in the
upper 50th percentile of Pediatric Risk of Mortality III scores and organ failure
also had significantly lower glucocorticoid receptor expression in CD4 and CD8
lymphocytes. There was no linear correlation between cortisol concentrations and
glucocorticoid receptor expression. CONCLUSIONS: Our study suggests that patients
with shock and increased severity of illness have lower glucocorticoid receptor
expression in CD4 and CD8 lymphocytes. Glucocorticoid receptor expression does
not correlate well with cortisol levels. Future studies could focus on studying
glucocorticoid receptor expression variability and isoform distribution in the
pediatric critically ill population as well as on different strategies to
optimize glucocorticoid response.
PMID- 25850868
TI - Asymmetric Copper-Catalyzed Vinylogous Mukaiyama Michael Addition of Cyclic
Dienol Silanes to Unsaturated alpha-Keto Phosphonates.
AB - A highly stereoselective vinylogous Mukaiyama Michael reaction (VMMR) leading to
alpha-keto phosphonate-containing gamma-butenolides with two stereogenic centers
is described. The presented transformation is catalyzed by a combination of a
commercially available C2 -symmetric bisoxazoline (BOX) ligand and a copper salt
and tolerates a variety of nucleophiles and electrophiles. The
stereoselectivities of the reactions are good to excellent and the products are
obtained in moderate to high yields.
PMID- 25850869
TI - Progressive swelling of the maxilla arising in the radiation site of a congenital
hemangioma in a 63-year-old woman.
PMID- 25850867
TI - Cerebrospinal Fluid Markers of Macrophage and Lymphocyte Activation After
Traumatic Brain Injury in Children.
AB - OBJECTIVES: The magnitude and role of the cellular immune response following
pediatric traumatic brain injury remains unknown. We tested the hypothesis that
macrophage/microglia and T-cell activation occurs following pediatric traumatic
brain injury by measuring cerebrospinal fluid levels of soluble cluster of
differentiation 163 and ferritin and soluble interleukin-2 receptor alpha,
respectively, and determined whether these biomarkers were associated with
relevant clinical variables and outcome. DESIGN: Retrospective analysis of
samples from an established, single-center cerebrospinal fluid bank. SETTING:
PICU in a tertiary children's hospital. PATIENTS: Sixty-six pediatric patients
after severe traumatic brain injury (Glasgow Coma Scale score < 8) who were 1
month to 16 years old and 17 control patients who were 1 month to 14 years old.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebrospinal fluid levels of
soluble cluster of differentiation 163, ferritin, and soluble interleukin-2
receptor alpha were determined by enzyme-linked immunosorbent assay at two time
points (t1 = 17 +/- 10 hr; t2 = 72 +/- 15 hr) for each traumatic brain injury
patient. Cerebrospinal fluid levels of soluble cluster of differentiation 163,
ferritin, and soluble interleukin-2 receptor alpha after traumatic brain injury
were compared with controls and analyzed for associations with age, patient sex,
initial Glasgow Coma Scale score, diagnosis of abusive head trauma, the presence
of hemorrhage on CT scan, and Glasgow Outcome Scale score. Cerebrospinal fluid
level of soluble cluster of differentiation 163 was increased in traumatic brain
injury patients at t2 versus t1 and controls (median, 95.4 ng/mL [interquartile
range, 21.8-134.0 ng/mL] vs 31.0 ng/mL [5.7-77.7 ng/mL] and 27.8 ng/mL [19.1-43.1
ng/mL], respectively; p < 0.05). Cerebrospinal fluid level of ferritin was
increased in traumatic brain injury patients at t2 and t1 versus controls (8.3
ng/mL [<7.5-19.8 ng/mL] and 8.9 ng/mL [<7.5-26.7 ng/mL] vs <7.5 ng/mL below lower
limit of detection, respectively; p < 0.05). Cerebrospinal fluid levels of
soluble interleukin-2 receptor alpha in traumatic brain injury patients at t2 and
t1 were not different versus controls. Multivariate regression revealed
associations between high ferritin and age 4 years or younger, lower Glasgow Coma
Scale score, abusive head trauma, and unfavorable Glasgow Outcome Scale score.
CONCLUSIONS: Children with traumatic brain injury demonstrate evidence for
macrophage activation after traumatic brain injury, and in terms of cerebrospinal
fluid ferritin, this appears more prominent with young age, initial injury
severity, abusive head trauma, and unfavorable outcome. Further study is needed
to determine whether biomarkers of macrophage activation may be used to
discriminate between aberrant and adaptive immune responses and whether
inflammation represents a therapeutic target after traumatic brain injury.
PMID- 25850870
TI - Surgical treatment of severe frontal bone fracture.
AB - Craniofacial trauma can lead to several complications. The combined fractures of
anterior and posterior walls of the frontal bone are almost always followed by
lesions in nasofrontal orifices and disruption of nasofrontal ostia or ducts, a
significant factor for the development of early and late complications after
sinus fractures. This article reports a case of trauma patient, who underwent
neurological evaluation and at first showed good general condition. Computed
tomography noted fracture of the anterior and posterior walls of the frontal
sinus and small foci of pneumocephalus in the cerebral cortex. The patient was
monitored periodically and 9 days after trauma showed increased areas of
pneumocephalus in prefrontal cortex, cerebrospinal fluid draining, and large dura
mater lesion, with signs of necrosis and inflammation (meningitis). The necrotic
tissues were removed, and dura mater was repaired through the approximation with
resorbable wire polyglactin 910 5-0, oxidized cellulose application, and bonding
with human fibrin sealant (fibrinogen, thrombin, and calcium chloride).
Sinusectomy, frontal sinus, and nasofrontal duct obliteration with pedicled
pericranium flap were performed. Tomographically, a reanatomization was noted in
frontal region, and a 12-month follow-up showed no complication. The use of
fibrin glue to repair dura mater lacerations, as well as the pedicle pericranium
flap for frontal sinus and nasofrontal duct obliteration, is an efficient method
for treating fractures of the frontal bone.
PMID- 25850871
TI - The importance of histopathologic analysis of pericoronal follicles for the early
identification of ameloblastomas.
AB - The objective of this study was to discuss the importance of performing
histopathological examination of pericoronal follicles as a routine procedure, so
as to enable the early identification of odontogenic lesions. We describe two
clinical cases with histopathological diagnoses of ameloblastomas who did not
show clinical or radiographic signs of disease before microscopic examination.
PMID- 25850872
TI - Giant nasal septal osteoma arising from perpendicular lamina of the ethmoid bone.
PMID- 25850873
TI - Pediatric craniofacial pseudoaneurysm with a variable history of antecedent
trauma.
AB - A pseudoaneurysm (PA) is a vascular lesion occurring along an artery most often
associated with previous trauma. It presents clinically as a compressible,
pulsatile mass, which can be painful, growing, and associated with headaches. We
report a series of 4 pediatric patients referred for management of a "cyst" who
had superficial craniofacial PAs arising in a variety of different locations with
a variable history of antecedent trauma.This is an institutional review board
approved study of 4 consecutive patients presenting to the pediatric plastic
surgery division with a diagnosis of PA between July 2012 and November 2013.The
patients were initially referred for management of cyst. Each presented with
compressible, pulsatile masses arising in varying locations along the superficial
temporal or occipital arteries of the face and scalp. Three of the patients did
not have a history of recent previous trauma. In the patients without history of
trauma, further workup with duplex ultrasound was performed. In cases where the
entire course of the artery could not be visualized by ultrasound, magnetic
resonance angiography was performed to rule out an intracranial source of the
lesion. Three lesions were excised with pathologic confirmation of the diagnosis
of PA. All masses and associated symptoms resolved after the
excision.Craniofacial PAs can occur in the pediatric population with a variable
history of antecedent trauma. Awareness of this clinical phenomenon can help
guide proper diagnosis for planning of safe, effective treatment. Surgical
excision provides a safe, aesthetic result.
PMID- 25850874
TI - Predictive variables derived from panoramic radiographs for impacted maxillary
cuspids treated with easy cuspid system.
AB - The aim of the current study was to find, by means of panoramic radiographs, a
viable statistical method to forecast the duration of orthodontic traction of
impacted maxillary cuspids. The treatment sample consisted of 51 palatal impacted
cuspids (19 unilateral and 32 bilateral) in 35 patients (aged between 10.5 and
17.5 y) with a cervical vertebral maturation between cervical stage 1 and 4. Each
patient underwent the same combined surgical-orthodontic technique. Anamnestic
data as well as pretreatment panoramic radiograph and cephalogram with European
Board of Orthodontics analysis were recorded for each case. Eight radiographic
indicators were derived from panoramic films to define the reliable position of
the impacted cuspid. Multiple regression analysis was used. All cuspids were
successfully treated with an average traction time of 99 days (range, 33-188 d).
The pretreatment radiographic features assessed on the panoramic radiographs did
not significantly affect the duration of traction. The formula based on alpha
angle, d1 distance, and S sector forecasted an average traction time of 123 days
(range, 63-210 d), which is longer than the real time. No relevant correlations
were found between orthodontic traction time and pretreatment radiograph
parameters derived from panoramic film at the beginning of the treatment. The
classic formula elaborated by Crescini could not be applied to the patients of
this study, who were treated with the Easy Cuspid method.
PMID- 25850875
TI - A new operative open-wings technique to correct the frontoforehead unit in
metopic synostosis.
AB - The technology adoption and creation of a multidisciplinary team have helped to
overcome the complexity associated. Craniofacial surgery has thus emerged from
the valuable contributions of neurosurgery, maxillofacial surgery, plastic
surgery, eyes, nose, and throat as well as head and neck surgery. A patient with
trigonocephaly may present a prominent "keel" forehead, accompanied by recession
of the lateral orbit rims, hypotelorism, and constriction of the anterior frontal
fossa when the metopic suture fuses before 6 months of age. In a period between
2007 and 2011, in the Salesi Children's Hospital, were treated for nonsyndromic
variety of metopic synostosis 11 infants; their ages ranged from 6 months to 9
months, and 7 were males and 4 females. The most important aims of our new
surgical technique are the achievement of symmetry as well as normal proportion
and reconstruction of the frontoforehead unit but remaining in a very
conservative treatment. The morphology and position of the supraorbital ridge
lateral orbital rim region are key elements of upper facial esthetics. This new
"open-wings" technique for the reconfiguration of the bilateral emisupraorbital
bar requires a midline incomplete osteotomy that involves only the internal
cortex of the frontonasal region. Hence, both lateral orbital walls are bent
inwardly and tilting forward, as in computed tomographic scan planning, with a
greenstick fracture pivoting on the preserved medial frontonasal region. This
open-wings conservative technique allows the avoidance of the most important
complication that may result in the traditional way such as dead space in the
anterior cranial fossa, infections, and blood loss but with an achievement of
satisfactory craniofacial form and aesthetic result.
PMID- 25850876
TI - The application of an ultrasonic bone aspirator for septoturbinoplasty.
AB - OBJECTIVE: The objectives of this study were to introduce the use of an
ultrasonic bone aspirator (UBA; SONOPET [Mutoh Co, Ltd, Tokyo, Japan]) for
septoturbinoplasty and to evaluate the efficacy and usefulness of this surgical
procedure. DESIGN: This was a retrospective chart review. SETTING: This study was
performed at a university medical center. METHODS: Of the 53 patients who
underwent septoturbinoplasty from July to October 2013, 30 were operated on using
a UBA and were enrolled in this study. Patients were followed for more than 6
months after surgery. Patterns of septal deviation and surgical results and
complications were investigated by paranasal sinus computed tomography scans,
nasal endoscopy, and acoustic rhinometry. Improvement of symptoms was measured
using the Nasal Obstruction Symptom Evaluation scale. RESULTS: Patterns of bony
septal deviation were classified as follows: localized septal bony spur or crest
(n = 7), basal bony septal deviation (n = 9), posterior bony septal deviation (n
= 8), bony spur with basal part deviation (n = 5), and basal and posterior bony
septal deviation (n = 1).Twenty-six patients underwent septoplasty with bilateral
inferior turbinate reduction surgery using either a microdebrider (n = 10) or a
microdebrider with UBA (n = 16). Four patients underwent septoplasty with
unilateral turbinate reduction surgery using a microdebrider and UBA. Based on
nasal endoscopic findings after surgery, 24 patients had a straight septum,
whereas 6 exhibited minimal remaining curvature. Subjective symptoms of nasal
obstruction evaluated using the visual analog scale and the Nasal Obstruction
Symptom Evaluation scale were improved in all patients. Surgery using a UBA
increased minimal cross-sectional area and nasal volume change in patients. There
were no significant complications related to UBA use such as saddle nose,
bleeding, or septal perforation. CONCLUSIONS: Application of a UBA for septo
turbinate surgery is an easy, safe, and effective method that reduces the
occurrence of common complications, such as septal perforation, delayed healing,
infection, and bleeding. In addition, the UBA produces minimal thermal and
mechanical injury to surrounding tissue and enables precise and incremental bone
removal with continuous irrigation and suction. This tool allows for easy
sculpting and reduction of bony architecture of the nasal cavity.
PMID- 25850877
TI - Simple resolution with maxillary o-ring attachment overdenture.
PMID- 25850878
TI - Myiasis in elderly involving oral and nasal cavities-diagnosis and treatment.
PMID- 25850879
TI - Examining the Time to Therapeutic Effect of Pregabalin in Spinal Cord Injury
Patients With Neuropathic Pain.
AB - PURPOSE: In 2 large-scale, placebo-controlled trials, pregabalin improved both
pain and pain-related sleep interference in patients with neuropathic pain due to
spinal cord injury (SCI). In both trials, pregabalin found statistically
significant improvement compared with placebo after 1 week of treatment. However,
the effects of pregabalin in the days immediately after initiation of treatment
are unknown. The purpose of the present analysis was to determine timing of
pregabalin's therapeutic effect in the days after initiation of treatment.
METHODS: Data were derived from 2 trials of pregabalin in patients with SCI
related neuropathic pain. Each day patients rated severity of pain and pain
related sleep interference over the past 24 hours on a scale from 0 to 10, with
higher scores indicating greater severity. To quantify timing of therapeutic
effect, we compared (pregabalin [vs] placebo) daily average pain and pain-related
sleep interference scores over the first 14 days of treatment. Significant
improvement was defined as the first day, of >=2 consecutive days, that
pregabalin significantly (P < 0.05) reduced mean scores compared with placebo. To
further quantify timing of therapeutic effect, each treatment group was examined
to determine the time required to achieve a >=1-point improvement in pain and
pain-related sleep interference score among patients with a clinically meaningful
and sustained response (>=30% improvement from baseline to end point) by using a
time-to-event analysis method. Kaplan-Meier analyses were used to estimate the
median (or 25th quartile) time (in days) required to achieve a >=1-point
improvement, among these responders, in pain and pain-related sleep interference
scores. Comparisons between pregabalin and placebo were made with a log-rank
test. FINDINGS: In both trials, significant improvement of pain and pain-related
sleep interference occurred within 2 days of initiating treatment with
pregabalin. Among patients reporting a clinically meaningful and sustained
response to treatment (patients with >=30% improvement from baseline to end
point), the time to a >=1-point improvement of pain and pain-related sleep
interference occurred significantly earlier among pregabalin-treated patients
than among placebo-treated patients. Finally, the timing of pregabalin's effect
on pain and pain-related sleep interference was unaffected by the use of
concomitant medications that were allowed for treatment of neuropathic pain in
both trials. IMPLICATIONS: Treatment with pregabalin results in rapid time to
significant improvement in both pain and pain-related sleep interference in
patients with neuropathic pain due to SCI. These findings should only be used as
a guide to physicians and patients as to when clinical response to pregabalin may
be expected.
PMID- 25850880
TI - Finding Truth in a World Full of Spin: Myth-Busting in the Case of Sovaldi.
AB - PURPOSE: Public discourse regarding the hepatitis C virus (HCV) drug Sovaldi(r)
(sofosbuvir) has become inflamed, generating much heat but little light
concerning the clinical, health economic, and quality-of-life merits of
Sovaldi(r). The purpose of this article is to provide a factual basis for
evaluating the claims regarding the benefits of Sovaldi(r) relative to its costs.
METHODS: A comprehensive review was conducted of news stories highlighted in the
daily updates of the electronic newsletters BIO SmartBrief, FiercePharma,
FierceBiotech and BioCentury Extra published from November 1, 2013, through
December 31, 2014, on the topics of the HCV market, Sovaldi(r), and other HCV
therapeutics. Also reviewed were recent practice guidelines on the management of
HCV infections, prescribing information on all HCV drugs approved by the US Food
and Drug Administration, and health technology assessments of Sovaldi(r) and
Harvoni(TM) (sofosbuvir/ledipasvir). FINDINGS: Sovaldi(r) and Harvoni(TM) have
provided significant improvements in the treatment of HCV, with all-oral regimens
and cure rates exceeding 90% in some populations of patients with HCV. Sovaldi(r)
prevents significant health care resource utilization in patients who would
otherwise develop cirrhosis and require a liver transplant; however, only a small
proportion of patients with HCV develop cirrhosis, and fewer require liver
transplants. Because it is not possible to identify those patients whose HCV will
progress to severe liver disease, it would be necessary to treat a large number
of patients with HCV to prevent disease progression in this subpopulation,
resulting in a considerable loss to health plans even over a 20-year horizon. The
claim that treating all patients with HCV with Sovaldi(r) would cost nearly as
much as the current total US expenditure on all prescription drugs, while
factually correct, is not a realistic scenario. Many patients with HCV will
continue to go undiagnosed. In addition, the medical expense for those who are
treated will be spread out over many years. However, the unexpectedly large, up
front cost of covering these drugs has had a major impact on health plan budgets,
resulting in losses for some plans. IMPLICATIONS: Sovaldi(r) represents an
enormous advance in the care of some populations of HCV-infected patients, but
also a major cost burden to health plans. As the first of a number of
anticipated, paradigm-changing drugs to treat medical conditions affecting large
patient populations, Sovaldi(r) should act as a wake-up call for all health care
stakeholders to engage in a meaningful, fact-based discussion about managing the
cost of innovative new drugs to balance the needs of drug manufacturers, health
plans, providers, and, above all, patients.
PMID- 25850882
TI - Evaluation of the anterior chamber angle in keratoconus and normal subjects.
AB - PURPOSE: To evaluate the anterior chamber angle in keratoconus eyes by use of the
VisanteTM OCT and OrbscanTM II. METHODS: Anterior chamber angle was measured with
the VisanteTM OCT and OrbscanTM II in 52 subjects, 26 KC subjects and 26 age and
control subjects. RESULTS: When comparing the nasal and temporal angles obtained
with the two techniques no correlation was found (R(2) always below 0.01) in
either the control subjects or in the KC subjects. Despite this, there was an
overall statistically significant difference in mean anterior chamber angles
(p<0.001) between VisanteTM OCT and OrbscanTM II. There was no statistical
difference (p>0.05) between nasal and temporal anterior chamber angles when
comparing controls and KC subjects with either of the two instruments. In
general, the VisanteTM OCT gave a smaller estimate of the anterior chamber angle.
CONCLUSION: The values from the VisanteTM OCT and OrbscanTM II cannot be
interchanged since the difference in measurement of the anterior chamber angle
was significantly different between the two instruments.
PMID- 25850883
TI - Dehydrocostus lactone suppressed the proliferation, migration, and invasion of
colorectal carcinoma through the downregulation of eIF4E expression.
AB - Dehydrocostus lactone (DHC) is the main active ingredient extracted from a
traditional Chinese medicine called Radix Aucklandiael. A few studies recently
showed that DHC has anticancer potential. However, no reports exist as yet on the
effects of DHC on colorectal carcinoma (CRC). This study aimed to determine
whether and how DHC functions in CRC cells. After treatment with DHC, both Lovo
and SW480 cells were significantly inhibited in their proliferation, cell cycle
progression, migration, and invasion abilities in a dose-dependent and/or
treatment time-dependent manner. Also, DHC significantly increased the apoptosis
rate of SW480 cells, but not Lovo cells. The expression of eukaryotic translation
initiation factor 4E (eIF4E), which was originally highly expressed in both
cells, was significantly decreased by DHC. The inhibition of proliferation,
migration, and invasion was significantly attenuated by the ectopic transfection
of eIF4E, and was promoted by the knockdown of eIF4E in Lovo cells. To the best
of our knowledge, this is the first time it has been shown that DHC suppressed
the proliferation, cell cycle progression, antiapoptosis, and migration and
invasion capabilities of CRC cells by the downregulation of eIF4E expression. In
terms of the overexpression of eIF4E in many cancers, it was speculated that DHC
might also play an anticancerous role by suppressing eIF4E expression. This
discovery could lay the foundations for advancing our understanding of the
anticancerous mechanism of DHC and developing DHC into a novel and effective
natural anticancer therapeutic.
PMID- 25850881
TI - A Randomized, Multicenter, Double-blind, Placebo-controlled, 3 * 3 Factorial
Design, Phase II Study to Evaluate the Efficacy and Safety of the Combination of
Fimasartan/Amlodipine in Patients With Essential Hypertension.
AB - PURPOSE: The objective of this study was to evaluate the efficacy and safety of a
fimasartan/amlodipine combination in patients with hypertension and to determine
the optimal composition for a future single-pill combination formulation.
METHODS: This Phase II study was conducted by using a randomized, multicenter,
double-blind, placebo-controlled, 3 * 3 factorial design. After a 2-week placebo
run-in period, eligible hypertensive patients (with a sitting diastolic blood
pressure [SiDBP] between 90 and 114 mm Hg) were randomized to treatment. They
received single or combined administration of fimasartan at 3 doses (0, 30, and
60 mg) and amlodipine at 3 doses (0, 5, and 10 mg) for 8 weeks. The primary
efficacy end point was the change in SiDBP from baseline and at week 8; secondary
end points included the change in SiDBP from baseline and at week 4 and the
changes in sitting systolic blood pressure from baseline and at weeks 4 and 8.
Treatment-emergent adverse events (AEs) were also assessed. FINDINGS: 420 Korean
patients with mild to moderate hypertension were randomly allocated to the 9
groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows:
placebo, -6.0 (8.5) mm Hg; amlodipine 5 mg, -10.6 (9.2) mm Hg; amlodipine 10 mg,
15.9 (7.2) mm Hg; fimasartan 30 mg, -10.1 (9.1) mm Hg; fimasartan 60 mg, -13.0
(10.0) mm Hg; fimasartan 30 mg/amlodipine 5 mg, -16.2 (8.5) mm Hg; fimasartan 30
mg/amlodipine 10 mg, -19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, -16.6
(6.9) mm Hg; and fimasartan 60 mg/amlodipine 10 mg, -21.5 (8.3) mm Hg. All
treatment groups produced significantly greater reductions in blood pressure
compared with the placebo group. In addition, all combination treatment groups
had superior reductions in blood pressure compared with the monotherapy groups.
In the combination treatment groups, doubling fimasartan dose in the given dose
of amlodipine did not show further BP reduction, whereas doubling amlodipine dose
showed significantly further BP reduction in the given dose of fimasartan. During
the study period, 75 (17.9%) of 419 patients experienced 110 AEs. Ninety-five AEs
were mild, 9 were moderate, and 6 were severe in intensity. Eight patients
discontinued the study due to AEs. There was no significant difference in
incidence of AEs among groups (P = 0.0884). The most common AE was headache (12
patients [2.9%]), followed by dizziness (11 patients [2.6%]) and elevated blood
creatine phosphokinase levels (6 patients [1.4%]). IMPLICATIONS: Fimasartan
combined with amlodipine produced superior blood pressure reductions and low
levels of AEs compared with either monotherapy. Therefore, a single-pill
combination with fimasartan 60 mg/amlodipine 10 mg will be developed.
ClinicalTrials.gov: NCT01518998.
PMID- 25850884
TI - Neutralization of the CD95 ligand by APG101 inhibits invasion of glioma cells in
vitro.
AB - Glioblastoma is a disease characterized by rapid invasive tumour growth. Studies
on the proapoptotic CD95/CD95L signalling pathway recently suggested a
significant contribution of CD95 signalling towards the high degree of motility
in glioma cells. Apogenix has developed APG101, a clinical phase II compound
designed to bind and neutralize CD95L, and thus to interfere with CD95/CD95L
based signalling. APG101 has shown clinical efficacy in a controlled randomized
phase II trial in patients with recurrent glioma. Because APG101 is not cytotoxic
to tumour cells in vitro, we postulated that the anti-invasive function of APG101
is the main mechanism of action for this compound. Using three-dimensional
spheroid invasion assays in vitro and in murine brain tissue cultures, we found
that knockdown of endogenous CD95L reduced the invasive phenotype in our two
glioblastoma model cell lines U87-MG and U251-MG. Invasion was restored in CD95L
knockdown cells upon the addition of soluble recombinant CD95L and this effect
was inhibited by APG101. We conclude that CD95L from autocrine and paracrine
sources contributes towards the invasive phenotype of glioblastoma cells and that
APG101 acts as a suppressor of proinvasive signalling by the CD95/CD95L pathway
in glioblastoma.
PMID- 25850885
TI - Gum chewing and gastrointestinal function following caesarean delivery: a
systematic review and meta-analysis.
AB - AIMS AND OBJECTIVES: The aims of this systematic review and meta-analysis were to
summarise current knowledge regarding gum chewing intervention for activation of
the gastrointestinal (GI) system following caesarean delivery. BACKGROUND: GI
symptoms such as nausea, vomiting and defecatory difficulties are bothersome for
women following a caesarean delivery. There is category A recommendation to not
withhold oral intake postoperatively. However, current practice guidelines vary
widely on time to initiate oral feeding post caesarean delivery, and additional
research is needed. Gum chewing has been shown to stimulate the GI system in
other postoperative patient populations. DESIGN: A systematic review and meta
analysis. METHODS: An electronic review was undertaken using the following
resources: PubMed (Medline), CINAHL, EMBASE and ClinicalTrials.gov databases. Key
words used in various combinations included cesarean section; cesarean delivery;
postoperative chewing gum; bowel movement; bowel function and complications.
RESULTS: A total of 171 articles were found of which 166 were excluded: 157 were
duplicates and the remainder did not meet the inclusion criteria. Five randomised
control trials were included in the meta-analysis, focusing on gum chewing as an
intervention as compared with a nongum chewing intervention, with a total of 846
participants. Compared with the nongum chewing group, gum chewing showed a
beneficial impact on the major outcomes of digestive system activation, including
bowel sound, gas passage and defecation. CONCLUSIONS: This meta-analysis supports
the effectiveness of gum chewing post caesarean delivery as a
noninvasive/nonpharmacological intervention for reactivation of bowel movement.
RELEVANCE TO CLINICAL PRACTICE: Gum chewing in the immediate postoperative period
following caesarean delivery may provide a socially acceptable, low-cost and safe
intervention to reduce postcaesarean delivery GI complications and restore GI
function.
PMID- 25850886
TI - Historical thinking in clinical medicine: lessons from R.G. Collingwood's
philosophy of history.
AB - The aim of this article is to create a space for historical thinking in medical
practice. To this end, we draw on the ideas of R.G. Collingwood (1889-1943), the
renowned British philosopher of history, and explore the implications of his
philosophy for clinical medicine. We show how Collingwood's philosophy provides a
compelling argument for the re-centring of medical practice around the patient
history as a means of restoring to the clinical encounter the human meaning that
is too often lost in modern medicine. Furthermore, we examine how Collingwood's
historical thinking offers a patient-centred epistemology and a more pluralistic
concept of evidence that includes the qualitative, narrative evidence necessary
for human understanding. We suggest that clinical medicine can benefit from
Collingwood's historical thinking, and, more generally, illustrates how a
philosophy of medicine that draws on diverse sources from the humanities offers a
richer, more empathetic clinical practice.
PMID- 25850887
TI - [Lingual neuromas in childhood as clue for diagnosis of the MEN 2B syndrome].
PMID- 25850888
TI - Modeling universal dynamics of cell spreading on elastic substrates.
AB - A three-dimensional (3D) multiscale moving contact line model is combined with a
soft matter cell model to study the universal dynamics of cell spreading over
elastic substrates. We have studied both the early stage and the late stage cell
spreading by taking into account the actin tension effect. In this work, the cell
is modeled as an active nematic droplet, and the substrate is modeled as a St.
Venant Kirchhoff elastic medium. A complete 3D simulation of cell spreading has
been carried out. The simulation results show that the spreading area versus
spreading time at different stages obeys specific power laws, which is in good
agreement with experimental data and theoretical prediction reported in the
literature. Moreover, the simulation results show that the substrate elasticity
may affect force dipole distribution inside the cell. The advantage of this
approach is that it combines the hydrodynamics of actin retrograde flow with
moving contact line model so that it can naturally include actin tension effect
resulting from actin polymerization and actomyosin contraction, and thus it might
be capable of simulating complex cellular scale phenomenon, such as cell
spreading or even crawling.
PMID- 25850889
TI - Value of CT findings to predict surgical ischemia in small bowel obstruction: A
systematic review and meta-analysis.
AB - PURPOSE: Our aim was to assess the diagnostic performance in determining
strangulation in small bowel obstruction (SBO) for five CT findings commonly
considered in published small bowel obstruction (SBO) management guidelines.
MATERIALS AND METHODS: Medical databases were searched for "bowel obstruction",
"computed tomography", "strangulation", and related terms. Two reviewers
independently selected articles for CT findings investigated with surgical or
histological reference standards for strangulation. Bivariate random-effects meta
analytical methods were used. RESULTS: A total of 768 patients, including 205
with strangulation from nine studies, were evaluated. The reduced bowel wall
enhancement CT sign had the highest specificity (95 %, CI 75-99), with a positive
LR of 11.07 (2.27-53.88) and DOR of 22.86 (4.99-104.61). The mesenteric fluid
sign had the highest sensitivity (89 %, CI 75-96) with a negative LR of 0.16
(0.07-0.39) and a DOR of 13.9 (5.73-33.75). The bowel wall thickness had a
sensitivity of 48 % (CI 41-54), a specificity of 83 % (CI 74-89), a positive LR
of 2.84 (1.83-4.41) and a negative LR of 0.62 (0.53-0.72). The other CT findings
had lower diagnostic performance. CONCLUSION: Two CT findings should be used in
clinical practice: reduced enhanced bowel wall is highly predictive of ischemia,
and absence of mesenteric fluid is a reliable finding to rule out strangulation.
KEY POINTS: * Reduced bowel wall enhancement on CT increases the probability of
strangulation 11-fold. * Absence of mesenteric fluid on CT decreases the
probability of strangulation 6-fold. * The clinical reliability of other CT signs
is doubtful for predicting strangulation.
PMID- 25850890
TI - Effect of TIPS placement on portal and splanchnic arterial blood flow in 4
dimensional flow MRI.
AB - OBJECTIVES: To assess changes in portal and splanchnic arterial haemodynamics in
patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) using
four-dimensional (4D) flow MRI, a non-invasive, non-contrast imaging technique.
METHODS: Eleven patients undergoing TIPS implantation were enrolled. K-t GRAPPA
accelerated non-contrast 4D flow MRI of the liver vasculature was applied with
acceleration factor R = 5 at 3Tesla. Flow analysis included three-dimensional
(3D) blood flow visualization using time-resolved 3D particle traces and semi
quantitative flow pattern grading. Quantitative evaluation entailed peak
velocities and net flows throughout the arterial and portal venous (PV) systems.
MRI measurements were taken within 24 h before and 4 weeks after TIPS placement.
RESULTS: Three-dimensional flow visualization with 4D flow MRI revealed good
image quality with minor limitations in PV flow. Quantitative analysis revealed a
significant increase in PV flow (562 +/- 373 ml/min before vs. 1831 +/- 965
ml/min after TIPS), in the hepatic artery (176 +/- 132 ml/min vs. 354 +/- 140
ml/min) and combined flow in splenic and superior mesenteric arteries (770 ml/min
vs. 1064 ml/min). Shunt-flow assessment demonstrated stenoses in two patients
confirmed and treated at TIPS revision. CONCLUSIONS: Four-dimensional flow MRI
might have the potential to give new information about the effect of TIPS
placement on hepatic perfusion. It may explain some unexpected findings in
clinical observation studies. KEY POINTS: * 4D flow MRI, a non-invasive, non
contrast imaging technique, is feasible after TIPS. * Provides visualization and
quantification of hepatic arterial, portal venous, collateral and TIPS
haemodynamics. * Better understanding of liver blood flow changes after TIPS and
patient management.
PMID- 25850891
TI - Optimizing computed tomography pulmonary angiography using right atrium bolus
monitoring combined with spontaneous respiration.
AB - OBJECTIVES: CT pulmonary angiography (CTPA) aims to provide pulmonary arterial
opacification in the absence of significant pulmonary venous filling. This
requires accurate timing of the imaging acquisition to ensure synchronization
with the peak pulmonary artery contrast concentration. This study was designed to
test the utility of right atrium (RA) monitoring in ensuring optimal timing of
CTPA acquisition. METHODS: Sixty patients referred for CTPA were divided into two
groups. Group A (n = 30): CTPA was performed using bolus triggering from the
pulmonary trunk, suspended respiration and 70 ml of contrast agent (CA). Group B
(n = 30): CTPA image acquisition was triggered using RA monitoring with
spontaneous respiration and 40 ml of CA. Image quality was compared. RESULTS:
Subjective image quality, average CT values of pulmonary arteries and density
difference between artery and vein pairs were significantly higher whereas CT
values of pulmonary veins were significantly lower in group B (all P < 0.05).
There was no significant difference between the groups in the proportion of
subjects where sixth grade pulmonary arteries were opacified (P > 0.05).
CONCLUSIONS: RA monitoring combined with spontaneous respiration to trigger image
acquisition in CTPA produces optimal contrast enhancement in pulmonary arterial
structures with minimal venous filling even with reduced doses of CA. KEY POINTS:
* Bolus tracking (BT) with pulmonary trunk monitoring is widely used in CTPA. *
Pulmonary venous contamination is a disadvantage of BT due to transition delay
time. * Right atrium monitoring with spontaneous respiration can optimize CTPA. *
It produces optimal contrast enhancement in pulmonary arteries with minimal
venous filling. * The contrast dose was significantly reduced.
PMID- 25850892
TI - Interreader and inter-test agreement in assessing treatment response following
transarterial embolization for hepatocellular carcinoma.
AB - PURPOSE: To evaluate interreader and inter-test agreement in applying size- and
necrosis-based response assessment criteria after transarterial embolization
(TAE) for hepatocellular carcinoma (HCC), applying two different methods of
European Association for the Study of the Liver (EASL) criteria. METHODS: Seventy
four patients (median age, 67 years) from a prospectively accrued study
population were included in this retrospective study. Four radiologists
independently evaluated CT data at 2-3 (1st follow-up, FU) and 10-12 (2nd FU)
weeks after TAE and assessed treatment response using size-based (WHO, RECIST)
and necrosis-based (mRECIST, EASL) criteria. Enhancing tissue was bidimensionally
measured (EASLmeas) and also visually estimated (EASLest). Interreader and inter
test agreements were assessed using intraclass correlation coefficient (ICC) and
kappa statistics. RESULTS: Interreader agreement for all response assessment
methods ranged from moderate to substantial (kappa = 0.578-0.700) at 1st FU and
was substantial (kappa = 0.716-0.780) at 2nd FU. Inter-test agreement was
substantial between WHO and RECIST (kappa = 0.610-0.799, 1st FU; kappa = 0.655
0.782, 2nd FU) and excellent between EASLmeas and EASLest (kappa = 0.899-0.918,
1st FU; kappa = 0.843-0.877, 2nd FU). CONCLUSION: Size- and necrosis-based
criteria both show moderate to excellent interreader agreement in evaluating
treatment response after TAE for HCC. Inter-test agreement regarding EASLmeas and
EASLest was excellent, suggesting that either may be used. KEY POINTS: * Applying
EASL criteria, visual estimation and bidimensional measurements show comparable
interreader agreement. * EASL meas and EASL est show substantial interreader
agreement for treatment response in HCC. * Agreement was excellent for EASL meas
and EASL est after TAE of HCC. * Visual estimation of enhancement is adequate to
assess treatment response of HCC.
PMID- 25850893
TI - The Complex Interaction Between Methamphetamine Abuse and HIV-1 Pathogenesis.
AB - The global HIV/AIDS pandemic has claimed the lives of an estimated 35 million
people. A significant barrier for combating this global pandemic is substance use
since it is associated with HIV transmission, delayed diagnosis/initiation of
therapy, and poor adherence to therapy. Clinical studies also suggest a link
between substance use and HIV-disease progression/AIDS-associated mortality.
Methamphetamine (METH) use is one of the fastest-growing substance use problems
in the world. METH use enhances high-risk sexual behaviors, therefore increases
the likelihood of HIV-1 acquisition. METH use is also associated with higher
viral loads, immune dysfunction, and antiretroviral resistance. Moreover, METH
use has also been correlated with rapid progression to AIDS. However, direct
effects of METH on HIV-1 disease progression remains poorly understood because
use of METH and other illicit drugs is often associated with reduced/non
adherence to ART. Nevertheless, in vitro studies demonstrate that METH increases
HIV-1 replication in cell cultures and animal models. Thus, it has been proposed
that METH's potentiating effects on HIV-1 replication may in part contribute to
the worsening of HIV-1 pathogenesis. However, our recent data demonstrate that
METH at physiologically relevant concentrations has no effect and at higher
concentrations inhibits HIV-1 replication in CD4+ T cells. Thus, the goal of this
review is to systematically examine the published literature to better understand
the complex interaction between METH abuse and HIV-1 disease progression.
PMID- 25850895
TI - Dramatic Improvement of Chronic Inflammatory Demyelinating Polyneuropathy Through
Tenofovir Treatment in a Patient Infected with Hepatitis B Virus.
PMID- 25850894
TI - Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism
Following Chronic Haloperidol Administration.
AB - Haloperidol is an effective antipsychotic drug for treatment of schizophrenia,
but prolonged use can lead to debilitating side effects. To better understand the
effects of long-term administration, we measured global metabolic changes in
mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead
to movement-related side effects in mice akin to those observed in patients after
prolonged use. Brain tissue was collected following microwave tissue fixation to
arrest metabolism and extracted metabolites were assessed using both liquid and
gas chromatography mass spectrometry (MS). Over 300 unique compounds were
identified across MS platforms. Haloperidol was found to be present in all test
samples and not in controls, indicating experimental validity. Twenty-one
compounds differed significantly between test and control groups at the p < 0.05
level. Top compounds were robust to analytical method, also being identified via
partial least squares discriminant analysis. Four compounds (sphinganine, N
acetylornithine, leucine and adenosine diphosphate) survived correction for
multiple testing in a non-parametric analysis using false discovery rate
threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05)
revealed significant findings for sphingolipid metabolism (p = 0.015) and protein
biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of
disruptions to myelin. This interpretation is supported by our observation of
elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004),
a marker previously associated with demyelination. This study further
demonstrates the utility of murine neurochemical metabolomics as a method to
advance understanding of CNS drug effects.
PMID- 25850896
TI - An intramolecular crossed-benzoin reaction based KCN fluorescent probe in aqueous
and biological environments.
AB - A turn-on fluorescent probe was designed for selective cyanide anion sensing in
aqueous and biological environments. The probe underwent an intramolecular
crossed-benzoin reaction in the presence of KCN to expel the fluorophore
resorufin. This probe was sensitive to KCN concentrations as low as 4 nM in
aqueous media.
PMID- 25850897
TI - The Role of Chronic Disease, Obesity, and Improved Treatment and Detection in
Accounting for the Rise in Healthcare Spending Between 1987 and 2011.
AB - BACKGROUND: To curb rising healthcare expenditures in the U.S.A., the factors
underlying this growth must be well understood. OBJECTIVE: We aim to explore how
chronic disease prevalence, obesity, and improved disease detection and treatment
rates contributed to the growth in health spending in the U.S.A. between 1987 and
2011. METHODS: We use spending decomposition equations to estimate the portion of
spending growth attributable to prevalence increases, rising treatment costs, and
population growth, respectively. We use two-part models to estimate the portion
of prevalence-related spending that is potentially due to obesity. We examine
changing diagnosis and treatment rates to assess how much of the growth in
spending might be desirable. RESULTS: We find that the share of total healthcare
spending associated with the treatment of chronic disease has risen dramatically
from 1987-2011. In particular, we estimate that 77.6% of healthcare spending
growth is attributable to patients with four or more chronic conditions. We find
that rising obesity levels may explain between 11.4 and 23.5% of the increase in
healthcare expenditure for several specific chronic conditions. Diagnosis and
treatment rates for chronic disease are improving. CONCLUSIONS: Individuals with
multiple chronic conditions are disproportionately responsible for rising
healthcare expenditure. Much of spending growth associated with rising rates of
chronic disease can be linked to rising obesity rates. Though much of the growth
in spending is generally considered undesirable, disease detection and treatment
rates are also rising, suggesting that at least some of the recent growth in
healthcare expenditure may be beneficial.
PMID- 25850898
TI - Human exposure to methylmercury from crayfish (Procambarus clarkii) in China.
AB - Methylmercury (MeHg) accumulation in aquatic food raises global concerns about
human exposure to MeHg. Crayfish is the world's third largest farmed crustacean
species and a favorite aquatic food in many countries. However, human health
hazard due to MeHg exposure via crayfish consumption is unclear, partly because
appropriate survey data are lacking. We report on mercury concentrations and
speciation in edible tail muscle of crayfish collected from restaurants in 23
Chinese cities. On average, MeHg constituted 99.1 % of mercury in tail muscle,
and MeHg concentrations were comparable with those reported for fish in China.
Variation in MeHg concentrations was not attributable to broad geographic region
(i.e., provinces) or tail length. For different populations, potential health
risk (characterized by hazard quotient or HQ) of MeHg exposure through crayfish
consumption depended largely on crayfish consumption rates. In particular, a
health hazard (HQ > 1) was found for high-rate consumers (i.e., 95 %ile or
higher) in some cities in the middle and lower reaches of the Yangtze River
(MLYR), during the peak consumption season. Our results suggest that more
attention should be paid to dietary MeHg intake via crayfish consumption in
China, particularly for communities with high consumption in MLYR.
PMID- 25850899
TI - The Targeted Delivery of Interleukin 4 Inhibits Development of Endometriotic
Lesions in a Mouse Model.
AB - Endometriosis is caused by the displacement of endometrium outside the uterus
contributing heavily to infertility and debilitating pelvic pain. Ectopic
adhesion and growth are believed to occur under the influence of a favorable
hormonal environment and immunological factors. The objective of this study is to
analyze the effect of a targeted therapy with an antibody-based pharmacodelivery
of interleukin 4 (F8-IL4) in a mouse model of experimentally induced
endometriosis. Endometriosis-like lesions were induced in Balb/c mice. The
animals were treated intravenously with F8-IL4 or with untargeted IL4 (KSF-IL4).
Twelve days after disease induction, the lesions were isolated. A significant
reduction in the number of total lesions/mouse and in the total volume of
lesions/mouse was observed in mice treated with F8-IL4 compared to controls (P =
.029 and P = .006, respectively), while no difference was found between KSF-IL4
treated mice and their controls. Gene expression was evaluated by quantitative
real-time polymerase chain reaction. Expression of genes involved in cell
adhesion, extracellular matrix invasion, and neovascularization was significantly
downregulated in F8-IL4-treated mice compared to their controls (integrin beta1:
P = .02; metalloproteinase [MMP] 3: P = .02; MMP9: P = .04; vascular endothelial
growth factor: P = .04). Gene expression of inflammatory cytokines (tumor
necrosis factor alpha, IL1beta, IL1alpha, and IL6) did not vary in the ectopic
lesions isolated from F8-IL4-treated mice compared to their controls.
Immunohistochemistry demonstrated a significantly reduced expression of E
cadherin and beta-catenin in the lesions of mice treated with F8-IL4. Our results
show that the antibody-mediated targeted delivery of IL4 inhibits the development
of endometriosis in a syngeneic mouse model by likely impairing adhesion,
invasion, and vascularization of the ectopic endometrium.
PMID- 25850900
TI - Functional patterns of cytomegalovirus (CMV) pp65 and immediate early-1-specific
CD8(+) T cells that are associated with protection from and control of CMV
DNAemia after allogeneic stem cell transplantation.
AB - BACKGROUND: The functional profile of cytomegalovirus (CMV)-specific CD8(+) T
cells that associate with protection from and control of CMV DNAemia in
allogeneic stem cell transplant (allo-SCT) recipients remains incompletely
characterized. METHODS: We enumerated pp65 and immediate early (IE)-1-specific
CD8(+) T cells expressing interferon-gamma, tumor necrosis factor-alpha, and
CD107a, by flow cytometry in 94 patients at days +30 and +60 after allo-SCT.
RESULTS: Fifty of 94 patients had CMV DNAemia within the first 100 days after
transplant. CMV-specific CD8(+) T-cell responses (of any functional type) were
more likely to be detected in patients who did not display CMV DNAemia than in
those who did (P = 0.04). Qualitatively, no major differences in the functional
signature of CMV-specific CD8(+) T cells were noted between patients who had or
did not have CMV DNAemia. Patients displaying levels of polyfunctional CD8(+) T
cells at day +30 >0.30 cell/MUL had a lower risk of CMV DNAemia (positive
predictive value 76%, and negative predictive value 43%). CONCLUSION: The
presence of polyfunctional CD8(+) T cells (either expressing CD107a or not) was
associated with lower levels of CMV replication, and higher frequency of self
resolved episodes. The data reported further clarify the role of polyfunctional
CD8(+) T cells in control of CMV DNAemia in allo-SCT recipients.
PMID- 25850901
TI - High expression of cytochrome b 5 reductase isoform 3/cytochrome b 5 system in
the cerebellum and pyramidal neurons of adult rat brain.
AB - Cytochrome b 5 reductase (Cb 5R) and cytochrome b 5 (Cb 5) form an enzymatic
redox system that plays many roles in mammalian cells. In the last 15 years, it
has been proposed that this system is involved in the recycling of ascorbate, a
vital antioxidant molecule in the brain and that its deregulation can lead to the
production of reactive oxygen species that play a major role in oxidative-induced
neuronal death. In this work, we have performed a regional and cellular
distribution study of the expression of this redox system in adult rat brain by
anti-Cb 5R isoform 3 and anti-Cb 5 antibodies. We found high expression levels in
cerebellar cortex, labeling heavily granule neurons and Purkinje cells, and in
structures such as the fastigial, interposed and dentate cerebellar nuclei. A
large part of Cb 5R isoform 3 in the cerebellum cortex was regionalized in close
proximity to the lipid raft-like nanodomains, labeled with cholera toxin B, as we
have shown by fluorescence resonance energy transfer imaging. In addition,
vestibular, reticular and motor nuclei located at the brain stem level and
pyramidal neurons of somatomotor areas of the brain cortex and of the hippocampus
have been also found to display high expression levels of these proteins. All
these results point out the enrichment of Cb 5R isoform 3/Cb 5 system in neuronal
cells and structures of the cerebellum and brain stem whose functional impairment
can account for neurological deficits reported in type II congenital
methemoglobinemia, as well as in brain areas highly prone to undergo oxidative
stress-induced neurodegeneration.
PMID- 25850902
TI - Alcohol and lithium have opposing effects on the period and phase of the
behavioral free-running activity rhythm.
AB - Bipolar patients have a high prevalence of comorbid alcohol use and abuse
disorders, while chronic alcohol drinking may increase the presence and severity
of certain symptoms of bipolar disorder. As such, there may be many individuals
that are prescribed lithium to alleviate the manic symptoms of bipolar disorder,
but also drink alcohol concurrently. In addition, both alcoholics and individuals
with bipolar disorder often exhibit disruptions to their sleep-wake cycles and
other circadian rhythms. Interestingly, both ethanol and lithium are known to
alter both the period and the phase of free-running rhythms in mammals. While
lithium is known to lengthen the period, ethanol seems to shorten the period and
attenuate the responses to acute light pulses. Therefore, the present study aimed
to determine whether ethanol and lithium have opposing effects on the circadian
pacemaker when administered together. C57BL/6J mice were provided drinking
solutions containing lithium, alcohol, or both, and their free-running rhythms
along with their response to photic phase shifts were investigated. Mice treated
with lithium displayed period lengthening, which was almost completely negated
when ethanol was added. Moreover, ethanol significantly attenuated light-induced
phase delays while the addition of lithium partially restored this response.
These results indicate that alcohol and lithium have opposing effects on
behavioral circadian rhythms. Individuals with bipolar disorder who are
prescribed lithium and who drink alcohol might be inadvertently altering their
sleep and circadian cycles, which may exacerbate their symptoms.
PMID- 25850903
TI - Physical Activity as an Intervention for Antenatal Depression: Rationale for
Developing Tailored Exercise Programs for Pregnant Women with Depression.
PMID- 25850904
TI - Ethnicity, deprivation and mortality due to 2009 pandemic influenza A(H1N1) in
England during the 2009/2010 pandemic and the first post-pandemic season.
AB - The relationship between risk of death following influenza A(H1N1)pdm09 infection
and ethnicity and deprivation during the 2009/2010 pandemic period and the first
post-pandemic season of 2010/2011 in England was examined. Poisson regression
models were used to estimate the mortality risk, adjusted for age, gender, and
place of residence. Those of non-White ethnicity experienced an increased
mortality risk compared to White populations during the 2009/2010 pandemic
[10.5/1000 vs. 6.0/1000 general population; adjusted risk ratio (RR) 1.84, 95%
confidence interval (CI) 1.39-2.54] with the highest risk in those of Pakistani
ethnicity. However, no significant difference between ethnicities was observed
during the following 2010/2011 season. Persons living in areas with the highest
level of deprivation had a significantly higher risk of death (RR 2.08, 95% CI
1.49-2.91) compared to the lowest level for both periods. These results highlight
the importance of rapid identification of groups at higher risk of severe disease
in the early stages of future pandemics to enable the implementation of optimal
prevention and control measures for vulnerable populations.
PMID- 25850905
TI - Periprosthetic BMD after cemented and uncemented total hip arthroplasty: a 10
year follow-up study.
AB - BACKGROUND AND PURPOSES: Insertion of a metallic implant into the femur changes
bone loading conditions and results in remodeling of femoral bone. To quantify
these changes in bone mineral density (BMD) after total hip arthroplasty, we
monitored femoral bone with dual X-ray absorptiometry (DXA). MATERIALS AND
METHODS: The periprosthetic bone mineral density was measured in seven Gruen
zones at scheduled time intervals during a 10-year follow-up. A total of 38
patients went through either cemented (n = 13) or uncemented arthroplasty (n =
25). RESULTS: During the 1st post-operative year BMD decreased markedly in both
groups mainly in the calcar area (Gruen zone 7); 21.9 % in the uncemented group
(p < 0.005) and 26.1 % in the cemented group (p < 0.005). After that there was a
slight continuous BMD loss in the proximal part of the femur and a slight
increase in the distal part of femur, especially after uncemented THA. In the non
operated control side, BMD showed only a slight decrease during the follow-up
(0.9 %, p = 0.003). INTERPRETATION: The study shows that when a good prosthesis
bone integration with or without cement is achieved, remodeling of the
periprosthetic bone decreases after the 1st post-operative year and the bone loss
reflects merely normal ageing.
PMID- 25850906
TI - Ongoing Stent Thrombosis: Optical Coherence Tomography Findings.
PMID- 25850907
TI - Amyloid and the cardiovascular system: A review of pathogenesis and pathology
with clinical correlations.
AB - The process of amyloidogenesis may complicate diverse disease states. It may be
systemic and have serious clinical sequelae; in other circumstances, it is a
localized phenomenon and functionally insignificant. In many cases its
manifestations may be predictable, with knowledge of the responsible protein.
Perhaps no organ system better exemplifies this than the cardiovascular one in
which amyloid may form from precursor proteins as varied as immunoglobulin light
chains, serum amyloid-A protein, transthyretin and its variants, atrial
natriuretic factor, beta2-microglobulin, and others. This review describes the
state of knowledge in relation to cardiovascular amyloidosis, with particular
emphasis on what is currently known about the pathogenesis of the process and the
related pathology of the various anatomic components of the cardiovascular
system.
PMID- 25850908
TI - Association of prenatal closure of the foramen ovale and fetal parvovirus B19
infection in hydrops fetalis.
AB - Stenosis of the foramen ovale was found at autopsy in a preterm hydropic female
who died 3 hours after birth. Subsequently, fetal infection by the human
parvovirus B19 was diagnosed by serology collected at autopsy and by identifying
the viral genome in both the placenta and autopsy liver by polymerase chain
reaction. Morphologic findings at autopsy suggested that the disease was in a
recovery phase. Prenatal closure of the foramen ovale, as an isolated lesion, is
a recognized association of fetal hydrops because right-to-left cardiac shunting
through the foramen is obligatory during fetal life. Parvovirus infection is also
associated with fetal hydrops, the mechanism being congestive heart failure
secondary to acute anemia. Coincidence in this case of both a cardiac and an
infective cause of fetal hydrops suggests that the two putative causes are
related. We suggest that an episode of fetal congestive heart failure (triggered
in this case by anemia caused by fetal parvovirus infection) may initiate
prenatal closure of a normally formed and previously patent foramen ovale. If
this is true, the congenital anatomic anomaly would represent a cardiac
deformation acquired during fetal life rather than a malformation dating from
embryonic life.
PMID- 25850909
TI - The cardiovascular pathology of phospholipid antibodies: An illustrative case and
review of the literature.
AB - There is some confusion in the literature regarding the pathology associated with
phospholipid antibodies. These antibodies, formed to a number of negatively
charged phospholipids, are associated with an increased tendency to both arterial
and venous thrombosis and embolism and may be manifest in a primary syndrome, a
syndrome secondary to systemic lupus erythematosis, or as an isolated phenomenon,
which may or may not be associated with thromboembolism. The pathogenesis of
thrombosis in these syndromes has not yet been elucidated. Indeed it is not even
clearly established that the antibodies have a pathogenic role, as opposed to
existing as an epiphenomenon or arising secondary to some form of vascular
damage. Clarification of the reported pathologic literature is needed as a basis
for studying the pathogenesis of thrombosis in these syndromes, and therefore we
present a review of papers that have reported pathology in association with
phospholipid antibodies. In order to illustrate the review, we present a typical
case of primary antiphospholipid antibody syndrome.
PMID- 25850910
TI - Subvalvular left ventricular outflow tract obstruction caused by "rhinonodular"
calcification.
AB - Cardiac calcification is a common problem in patients with renal failure.
Calcific deposits often affect the mitral annulus, the aortic valve, and the
coronary arteries. We report an atypical case of cardiac calcification
obstructing the left ventricular outflow tract with minimal aortic valve
calcification.
PMID- 25850911
TI - A case of giant cell myocarditis with evidence of cardiac autoimmunity.
AB - A 45-year-old-woman with giant cell myocarditis showing high titer of circulating
antiheart antibodies is reported. She experienced two recurrences of myocarditis
and repeatedly responded to immunosuppressive therapy using prednisolone. The
titer of antiheart antibodies went up and down appropriately according to the
clinical responses to immunosuppressive therapy. This case suggested that giant
cell myocarditis might be related to autoimmunity.
PMID- 25850912
TI - The effect of prefixation on the quality of vascular corrosion casts of rat
heart.
AB - To help define the optimal conditions for the preparation of vascular corrosion
casts of rat heart, we examined the effect of prefixation with aldehyde fixatives
on the perfusion rates of rat heart and on the quality of vascular casts. For
these studies, beating hearts were removed from rats, cannulated via the aortic
stump, arrested with KCl, perfused retrograde with buffered saline or fixative,
and infused with resin to prepare corrosion casts. Fixatives used were 2.5%
glutaraldehyde or 2% paraformaldehyde, and the casting resin consisted of a
Mercox-methylmethacrylate mixture (4:1). All perfusion pressures were monitored
at 80 to 100 mm Hg using a mercury manometer. The perfusion rate of control
hearts was 13 to 14 mL/min. Prefixation with glutaraldehyde and paraformaldehyde
reduced perfusion to 8.5 and 8.1 mL/min, respectively. Cast quality was observed
grossly and with the scanning electron microscope. Control hearts yielded high
quality, complete casts with 2570 capillaries/mm(2+). Casts from prefixed hearts
exhibited areas of incomplete vessel filling and resisted complete tissue
maceration, leaving tissue remnants adhering to the vessel replicas. Casts from
glutaraldehyde-fixed hearts were of very poor quality. Our results indicate that
prefixation is an unnecessary step in the preparation of vascular casts of rat
heart and is inconsistent with cast quality.
PMID- 25850913
TI - CD30 positive (Ki-1) large cell lymphoma presenting with pericardial
constriction.
AB - It is very uncommon for the initial presentation of malignant lymphoma to be one
of cardiac involvement and for such involvement to precipitate cardiac
dysfunction attributable to constriction. We describe a CD30 positive (Ki-1)
anaplastic large cell lymphoma, T-cell type, in a 29-year-old man whose
presentation was a short history of profound hemodynamic impairment and whose
clinical course was rapidly fatal. This patient's constrictive physiology was
attributable to diffuse infiltration of the pericardium and epicardium by the Ki
1 lymphoma. Our description of this patient is noteworthy, given that the
clinical and pathologic features of Ki-1 lymphomas are still being characterized.
PMID- 25850914
TI - Primary undifferentiated sarcoma of the pericardium.
AB - A 60-year-old woman was found to have a pericardial mass on two-dimensional
echocardiography and computerized tomography. At autopsy, there was a large tumor
arising from the epicardial surface of the left ventricle. The tumor encircled
the great arteries and invaded the wall of the pulmonary artery. Microscopic
examination showed features of an undifferentiated sarcoma.
PMID- 25850915
TI - Coronary artery dissection.
PMID- 25850916
TI - The Arnold Berliner Award 2015.
PMID- 25850918
TI - Plateletcrit May Not be a Marker for Recurrent Pregnancy Loss.
PMID- 25850917
TI - Recurrence of Venous Thromboembolism in Patients With Cancer Treated With
Warfarin.
AB - Venous thromboembolism (VTE) is a common complication in patients with cancer.
Previous randomized studies have demonstrated that the rates of recurrent VTE are
lower in patients treated with low-molecular-weight heparin compared to warfarin.
We performed a retrospective analysis of 236 patients with cancer managed by a
dedicated oncology anticoagulation management service to compare "real-world"
rates of recurrent VTE and bleeding in patients treated with warfarin versus
parenteral anticoagulants. Initial anticoagulant regimen included a parenteral
agent with transition to warfarin in 132 (55.9%) patients, enoxaparin in 53
(22.5%), dalteparin in 37 (15.7%), and fondaparinux in 14 (5.9%). Taking into
account the competing risk of death, cumulative incidence of VTE recurrence at 6
months was 4.0% with warfarin, 10.3% with enoxaparin, 3.0% with dalteparin, and
7.7% with fondaparinux (P = .004). Bleeding complications occurred in 10.6% of
patients on warfarin, 17.0% on enoxaparin, 27.0% on dalteparin, and 14.3% on
fondaparinux (P = .089). In a dedicated anticoagulation clinic, specific for
patients with cancer, warfarin may be an acceptable treatment for first
thrombotic events in patients with cancer.
PMID- 25850919
TI - Early Modification in Drainage of Interleukin-1beta and Tumor Necrosis Factor
alpha Best Predicts Surgical-Site Infection After Cervical Neck Dissection for
Oral Cancer.
AB - PURPOSE: Surgical-site infection (SSI) after cervical neck dissection (CND) for
head and neck squamous cell carcinoma (HNSCC) increases morbidity and delays
adjuvant treatment. This study assessed changes in cytokines levels in
postsurgical drainage fluid after CND and examined their predictive value for the
early diagnosis of SSI. PATIENTS AND METHODS: An observational prospective pilot
study was conducted in 39 consecutively recruited patients with HNSCC undergoing
CND who were treated at the authors' service within the past 2 years. Patients
met the following inclusion criteria: no previous chemotherapy or radiotherapy,
closed-suction drainage, 30-day follow-up, prophylactic treatment with
amoxicillin plus clavulanic acid and dexamethasone, no chronic inflammatory
disease, and no previous neck surgery. Drainage samples were collected at
postoperative days +1 and +3. Sample size was estimated based on SSI incidence
after HNSCC surgery (~15%; alpha risk, 0.05; beta risk, 0.2; 2-sided test).
Interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha
(TNF-alpha) levels were measured. Patients were followed to detect SSI.
Sensitivity, specificity, and prognostic values were calculated for each cytokine
at days +1 and +3 to diagnose SSI. RESULTS: SSI was diagnosed in 6 of 39
patients. Bilateral CND, tracheostomy, surgery duration longer than 7 hours,
HNSCC stage T3 or T4, and reconstruction with pedicled flaps versus microvascular
flaps for advanced-stage tumors were considered risk factors for SSI. All
cytokines except IL-10 showed statistical differences between patients with SSI
and those without SSI. The best receiver operating characteristic curves yielded
cutoff values at day +1 (TNF-alpha >14.5 pg/mL; sensitivity, 100%; specificity,
87.88%) and day +3 (IL-1beta >115 pg/mL; sensitivity, 83.33%; specificity,
78.79%). Also, IL-2 levels higher than 6.5 pg/mL at day +1 (sensitivity, 83.33%;
specificity, 69.7%) and day +3 (sensitivity, 100%; specificity, 69.7%) and IL-6
levels higher than 3,300 pg/mL at day +3 (sensitivity, 100%; specificity, 60.61%)
yielded adequate diagnostic profitability. CONCLUSION: The results of this study
suggest that the assessment of cytokine levels in drainage fluid soon after CND
could provide a novel method for the early detection of SSI.
PMID- 25850920
TI - Treatment of Parotid Malignancies-10 Years of Experience.
AB - PURPOSE: Operative treatment is the main treatment option for parotid gland
tumors. The purpose of this study was to present the authors' experience in the
operative treatment of parotid gland malignant tumors, especially regarding
feasibility and techniques in the most advanced cases. MATERIALS AND METHODS:
This is a retrospective cohort study of parotid malignancies. The study included
patients treated at the authors' university clinic from 2000 through 2010. The
primary predictor variable was stage of disease. The primary outcome variables
were 3- and 5-year overall and disease-free survival rates. The secondary
predictor variables were nodal status, distant metastases, status of the facial
nerve (FN), tumor diameter, extraparotid tumor extension, histology, and surgical
procedure. The outcome variable was survival rate. Data were analyzed by chi(2)
tests. RESULTS: Of 867 parotid tumors, 103 patients with malignancies (47 female,
56 male; 12 to 88 yr old) underwent 24 partial lateral, 34 lateral, 39 total, and
6 extended parotidectomies. The 3- and 5-year overall survival and 3- and 5-year
disease-free survival rates for stages T1 and T2 were 100, 99, 91, and 85%,
respectively, and those for stages T3 and T4 were 100, 70, 48, and 34%,
respectively. Overall and disease-free survival rates were influenced by FN
paralysis and histologic type. CONCLUSIONS: Final oncologic outcomes, recurrence,
and survival rates in parotid malignancies are considerably affected by local
tumor stage, malignancy, and FN paralysis before treatment. Infiltration of
adjacent structures is not connected with a poorer prognosis as long as an
extended parotidectomy is performed.
PMID- 25850921
TI - Responses of skeletal muscles to gravitational unloading and/or reloading.
AB - Adaptation of morphological, metabolic, and contractile properties of skeletal
muscles to inhibition of antigravity activities by exposure to a microgravity
environment or by simulation models, such as chronic bedrest in humans or
hindlimb suspension in rodents, has been well reported. Such physiological
adaptations are generally detrimental in daily life on earth. Since the
development of suitable countermeasure(s) is essential to prevent or inhibit
these adaptations, effects of neural, mechanical, and metabolic factors on these
properties in both humans and animals were reviewed. Special attention was paid
to the roles of the motoneurons (both efferent and afferent neurograms) and
electromyogram activities as the neural factors, force development, and/or length
of sarcomeres as the mechanical factors and mitochondrial bioenergetics as the
metabolic factors.
PMID- 25850922
TI - A protein tyrosine kinase receptor, c-RET signaling pathway contributes to the
enteric neurogenesis induced by a 5-HT4 receptor agonist at an anastomosis after
transection of the gut in rodents.
AB - We previously reported that a serotonin 4 (5-HT4) receptor agonist, mosapride
citrate (MOS), increased the number of c-RET-positive cells and levels of c-RET
mRNA in gel sponge implanted in the necks of rats. The 5-HT4 receptor is a G
protein coupled receptor (GPCR) coupled to G protein Gs-cAMP cascades. We
investigated the possibility that 5-HT4 receptor activation induced c-RET
activation and/or PKA activation by elevating cAMP levels. Rodents were orally
administered MOS by adding it to drinking water for 2 weeks after enteric nerve
circuit insult via gut transection and anastomosis, together with the RET
inhibitors withaferin A (WA) and RPI-1 or the PKA inhibitor H89. We then examined
PGP9.5-positive cells in the newly formed granulation tissue at the anastomotic
site. MOS significantly increased the number of new neurons, but not when co
administered with WA or RPI-1. Co-administration of H89 failed to alter MOS
induced increases in neurogenesis. In conclusion, the c-RET signaling pathway
contributes to enteric neurogenesis facilitated by MOS, though the contribution
of PKA activation seems unlikely.
PMID- 25850923
TI - The cutaneous vasoconstrictor response in lower extremities during whole-body and
local skin cooling in young women with a cold constitution.
AB - To clarify the characteristics of the thermal control of skin blood flow (SkBF)
in individuals with a cold constitution, we examined the cutaneous
vasoconstrictor responses in the calf and dorsal foot during whole-body and local
skin cooling in young women complaining of chilliness (C group) and young women
not suffering from it (N group). During whole-body skin cooling, the
vasoconstrictor sensitivity in the dorsal foot, but not in the calf, was greater
in the C group than in the N group. The C group also showed greater
vasoconstrictor responses in the dorsal foot, but not in the calf, during local
skin cooling and the iontophoretic application of norepinephrine. These findings
suggest that the C group possesses a specific SkBF controlling system that is
characterized by higher adrenergic sensitivity for greater cutaneous
vasoconstriction in the distal portion of the lower extremities during cold
exposure.
PMID- 25850924
TI - Intraoperative determination of the adequacy of myotomy length during peroral
endoscopic myotomy (POEM): the double-endoscope transillumination for extent
confirmation technique (DETECT).
AB - BACKGROUND AND STUDY AIMS: Precise identification of the gastroesophageal
junction (GEJ) is a challenging prerequisite for adequate length of an esophageal
myotomy. Multiple standard methods to identify the GEJ have been described;
however, a more objective modality is needed to ensure effective peroral
endoscopic myotomy (POEM). PATIENTS AND METHODS: In the double-endoscope
transillumination for extent confirmation technique (DETECT), an ultraslim
gastroscope is passed to the most distal aspect of the submucosal tunnel created
during POEM. A regular gastroscope is advanced into the stomach, and the
visualization of transillumination from the ultraslim gastroscope enables
identification of the extent of the submucosal tunnel. RESULTS: A total of 10
patients underwent POEM with DETECT. Initial submucosal tunneling was performed
based on a determination of the GEJ location via standard methods. DETECT
indicated the tunnel extent to be inadequate in 50% of patients, and the tunnel
was extended a further 1 to 2cm. The mean initial tunnel length was 15.4cm, with
a mean initial myotomy length of 11.9cm. DETECT was performed in less than 10
minutes without complications. CONCLUSION: DETECT is an objective method for
determining the adequacy of the submucosal tunnel length during POEM.
PMID- 25850926
TI - A causal role of the right inferior frontal cortex in implementing strategies for
multi-component behaviour.
AB - Everyday activities, such as, for example, driving a car or preparing a meal,
require the hierarchical organization and processing of several individual
actions. Currently, the neural mechanisms underlying the control of action
sequences are not well understood. Here, the authors demonstrate that the right
inferior frontal gyrus (rIFG) plays a key role in implementing the strategy used
to cascade different actions. Continuous theta burst stimulation (TBS) applied to
the rIFG results in a less efficient action cascading strategy, whereas
intermittent TBS results in a more efficient strategy, compared with a shamTBS
control condition. These effects are confirmed in electrophysiological data
showing that activity differences in the rIFG are related to alterations in
response selection processes. Overall, these results suggest that the neural
dynamics of the rIFG determine the strategy used during some forms of everyday
multi-component behaviour.
PMID- 25850927
TI - A Taenia crassiceps factor induces apoptosis of spleen CD4+T cells and TFG-beta
and Foxp3 gene expression in mice.
AB - This study was undertaken to determine whether a parasite substance produces
structural pathology in the mouse spleen. A low-molecular-weight Taenia
crassiceps metacestode factor (MF) isolated from the peritoneal fluid of female
mice infected with T. crassiceps metacestodes induced pathological and
immunological changes in mouse spleen cells in vivo. Electron microscopy and
confocal microscopy revealed severe changes in the spleen histoarchitecture of T.
crassiceps-infected and MF-treated mice. Apoptotic degenerated spleen cells were
observed in the white and red pulps and were more conspicuous in the white pulp
of the spleen from the T. crassiceps-infected mice than in that of the MF-treated
mice. Flow cytometry analysis revealed that the numbers of spleen CD4+T cells
were significantly lower in both experimental groups than in control mice. The ex
vivo expression of transforming growth factor (TGF)-beta and factor Foxp3 were
significantly higher in splenocytes of the experimental mice than the basal
expression observed in the control cells. These findings may have potential
applications for a better understanding of the host-parasite relationship in
human neurocysticercosis.
PMID- 25850929
TI - Current radiation therapy techniques for lung cancer and its importance for
suitable radiological assessment of treatment response in lung cancer.
PMID- 25850928
TI - The inconspicuous penis in children.
AB - The term 'inconspicuous penis' refers to a group of anatomical abnormalities in
which the penis looks smaller than is expected. Micropenis can be defined as
'true micropenis'--which results from a defect in the hypothalamic-pituitary
gonadal axis--and 'micropenis secondary to congenital anatomical anomalies of the
surrounding and overlying structures'--also known as 'concealed penis'. The
different forms of concealed penis include webbed penis, congenital megaprepuce
and partially hidden penis caused by prepubic adiposity. This disorder can also
have iatrogenic causes resulting from adhesions that are secondary to
circumcision--this type of concealed penis is known as 'trapped penis'. However,
in both groups, micropenis is defined as a stretched penile length that is at
least 2.5 SD below the mean for the patient's age, but without any other penile
defects. Patients with true micropenis can be managed with testosterone, which
has demonstrated good penile elongation results in the long term. Surgery also
has a pivotal role in reconstruction for elongating the penis and for correction
of anatomical abnormalities in concealed penis.
PMID- 25850930
TI - Distinct methylation patterns in genes that affect mitochondrial function are
associated with kidney disease in blood-derived DNA from individuals with Type 1
diabetes.
AB - AIMS: Epigenetic modifications, such as DNA methylation, can influence the risk
of developing kidney disease. We studied methylation profiles in genes related to
mitochondrial function to assess whether differences in these epigenetic features
were associated with diabetic kidney disease in people with Type 1 diabetes.
METHODS: A case-control association study was undertaken (n = 196 individuals
with diabetic kidney disease vs. n = 246 individuals without renal disease).
Participants were White and diagnosed with Type 1 diabetes before 31 years of
age. Genes that encode mitochondrial proteins (n = 780) were downloaded from
mitoproteome.org. DNA methylation profiles from blood-derived DNA were generated
using the Illumina Infinium HumanMethylation450 (262 samples) and Illumina
Infinium HumanMethylation27 (192 samples) arrays. Beta values (beta) were
calculated and quality control was conducted, including evaluating blind
duplicate DNA samples. RESULTS: Fifty-four Cytosine-phosphate-Guanine probes
across 51 unique genes were significantly associated (P <= 10(-8) ) with diabetic
kidney disease across both the 450K and the 27K methylation arrays. A
subanalysis, employing the 450K array, identified 755 Cytosine-phosphate-Guanine
probes in 374 genes that were significantly associated (P <= 10(-8) ) with end
stage renal disease. Forty-six of the top-ranked variants for diabetic kidney
disease were also identified as being differentially methylated in individuals
with end-stage renal disease. The largest change in methylation (Deltabeta = 0.2)
was observed for cg03169527 in the TAMM41 gene, chromosome 3p25.2. Three genes,
PMPCB, TSFM and AUH, were observed with differential methylation at multiple
Cytosine-phosphate-Guanine sites each (P < 10(-12) ). CONCLUSIONS: Differential
methylation in genes that influence mitochondrial function are associated with
kidney disease in individuals with Type 1 diabetes.
PMID- 25850932
TI - Self-assembled peptide nanoarchitectures: applications and future aspects.
AB - Among the diversity of natural and synthetic compounds being studied and applied
for human welfare, peptides able to develop nanostructures are currently under
special attention of scientists. In this review, we focus on such properties of
peptides and various kinds of intramolecular interactions allowing their ability
to form different shapes of nanoassemblies. We have also discussed the
applications of self-assembled peptides in various biomedical fields where they
can be employed as cargo to target delivery of drugs, genes, in tissue
engineering, regenerative medicines, and biosensors.
PMID- 25850931
TI - Breast cancer subtype intertumor heterogeneity: MRI-based features predict
results of a genomic assay.
AB - PURPOSE: To investigate the association between a validated, gene-expression
based, aggressiveness assay, Oncotype Dx RS, and morphological and texture-based
image features extracted from magnetic resonance imaging (MRI). MATERIALS AND
METHODS: This retrospective study received Internal Review Board approval and
need for informed consent was waived. Between 2006-2012, we identified breast
cancer patients with: 1) ER+, PR+, and HER2- invasive ductal carcinoma (IDC); 2)
preoperative breast MRI; and 3) Oncotype Dx RS test results. Extracted features
included morphological, histogram, and gray-scale correlation matrix (GLCM)-based
texture features computed from tumors contoured on pre- and three postcontrast MR
images. Linear regression analysis was performed to investigate the association
between Oncotype Dx RS and different clinical, pathologic, and imaging features.
P < 0.05 was considered statistically significant. RESULTS: Ninety-five patients
with IDC were included with a median Oncotype Dx RS of 16 (range: 0-45). Using
stepwise multiple linear regression modeling, two MR-derived image features,
kurtosis in the first and third postcontrast images and histologic nuclear grade,
were found to be significantly correlated with the Oncotype Dx RS with P =
0.0056, 0.0005, and 0.0105, respectively. The overall model resulted in
statistically significant correlation with Oncotype Dx RS with an R-squared value
of 0.23 (adjusted R-squared = 0.20; P = 0.0002) and a Spearman's rank correlation
coefficient of 0.49 (P < 0.0001). CONCLUSION: A model for IDC using imaging and
pathology information correlates with Oncotype Dx RS scores, suggesting that
image-based features could also predict the likelihood of recurrence and
magnitude of chemotherapy benefit.
PMID- 25850933
TI - Liquid-liquid phase separation in aerosol particles: imaging at the nanometer
scale.
AB - Atmospheric aerosols can undergo phase transitions including liquid-liquid phase
separation (LLPS) while responding to changes in the ambient relative humidity
(RH). Here, we report results of chemical imaging experiments using environmental
scanning electron microscopy (ESEM) and scanning transmission X-ray microscopy
(STXM) to investigate the LLPS of micrometer-sized particles undergoing a full
hydration-dehydration cycle. Internally mixed particles composed of ammonium
sulfate (AS) and either: limonene secondary organic carbon (LSOC), alpha, 4
dihydroxy-3-methoxybenzeneaceticacid (HMMA), or polyethylene glycol (PEG-400)
were studied. Events of LLPS were observed for all samples with both techniques.
Chemical imaging with STXM showed that both LSOC/AS and HMMA/AS particles were
never homogeneously mixed for all measured RH's above the deliquescence point and
that the majority of the organic component was located in the outer phase. The
outer phase composition was estimated as 65:35 organic: inorganic in LSOC/AS and
as 50:50 organic: inorganic for HMMA/AS. PEG-400/AS particles showed fully
homogeneous mixtures at high RH and phase separated below 89-92% RH with an
estimated 70:30% organic to inorganic mix in the outer phase. These two chemical
imaging techniques are well suited for in situ analysis of the hygroscopic
behavior, phase separation, and surface composition of collected ambient aerosol
particles.
PMID- 25850934
TI - Attenuated SAG expression exacerbates 4-hydroxy-2-nonenal-induced apoptosis and
hypertrophy of H9c2 cardiomyocytes.
AB - Oxidative stress, associated with the accumulation of reactive oxygen species
(ROS), results in numerous and detrimental effects on the myocardium such as the
induction of apoptotic cell death, hypertrophy, fibrosis, dysfunction, and
dilatation. The product of sensitive to apoptosis gene (SAG) is a RING finger
protein that has been shown to have a protective effect against apoptosis induced
by oxidative stress in various cell types. The major reactive aldehydic product
of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is believed to be largely
responsible for cytopathological effects observed during oxidative stress. In the
present study, we showed that the transfection of H9c2 clonal myoblastic cells
with small interfering RNA (siRNA) specific for SAG markedly attenuated SAG
expression and exacerbates HNE-induced apoptosis and hypertrophy. The knockdown
of SAG expression resulted in the modulation of cellular redox status,
mitochondrial function, and cellular oxidative damage. Taken together, our
results showed that the suppression of SAG expression by siRNA enhanced HNE
induced apoptosis and hypertrophy of cultured cardiomyocytes via the disruption
of the cellular redox balance. Given the importance of the SAG protein in the
regulation of the redox status of cardiomyocytes, we conclude that this protein
may be a potential new target in the development of therapeutic agents for the
prevention of cardiovascular diseases.
PMID- 25850935
TI - Onset of photosynthesis in spring speeds up monoterpene synthesis and leads to
emission bursts.
AB - Emissions of biogenic volatile organic compounds (BVOC) by boreal evergreen trees
have strong seasonality, with low emission rates during photosynthetically
inactive winter and increasing rates towards summer. Yet, the regulation of this
seasonality remains unclear. We measured in situ monoterpene emissions from Scots
pine shoots during several spring periods and analysed their dynamics in
connection with the spring recovery of photosynthesis. We found high emission
peaks caused by enhanced monoterpene synthesis consistently during every spring
period (monoterpene emission bursts, MEB). The timing of the MEBs varied
relatively little between the spring periods. The timing of the MEBs showed good
agreement with the photosynthetic spring recovery, which was studied with
simultaneous measurements of chlorophyll fluorescence, CO2 exchange and a simple,
temperature history-based proxy for state of photosynthetic acclimation, S. We
conclude that the MEBs were related to the early stages of photosynthetic
recovery, when the efficiency of photosynthetic carbon reactions is still low
whereas the light harvesting machinery actively absorbs light energy. This
suggests that the MEBs may serve a protective functional role for the foliage
during this critical transitory state and that these high emission peaks may
contribute to atmospheric chemistry in the boreal forest in springtime.
PMID- 25850937
TI - Localization of the Trace Elements Iron, Zinc and Selenium in Relation to
Anatomical Structures in Bovine Ovaries by X-Ray Fluorescence Imaging.
AB - X-ray fluorescence (XRF) was used to image 40 histological cross-sections of
bovine ovaries (n=19), focusing on structures including: antral follicles at
different stages of growth or atresia, corpora lutea at three stages of
development (II-IV), and capillaries, arterioles, and other blood vessels. This
method identified three key trace elements [iron (Fe), zinc (Zn), and selenium
(Se)] within the ovarian tissue which appeared to be localized to specific
structures. Owing to minimal preprocessing of the ovaries, important high
resolution information regarding the spatial distribution of these elements was
obtained with elemental trends and colocalizations of Fe and Zn apparent, as well
as the infrequent appearance of Se surrounding the antrum of large follicles, as
previously reported. The ability to use synchrotron radiation to measure trace
element distributions in bovine ovaries at such high resolution and over such
large areas could have a significant impact on understanding the mechanisms of
ovarian development. This research is intended to form a baseline study of
healthy ovaries which can later be extended to disease states, thereby improving
our current understanding of infertility and endocrine diseases involving the
ovary.
PMID- 25850939
TI - Ratio of neutrophilic CD64 and monocytic HLA-DR: A novel parameter in diagnosis
and prognostication of neonatal sepsis.
AB - OBJECTIVE: Approaches to monitoring of sepsis have traditionally relied upon the
pro-inflammatory component of the sepsis response. This study evaluated the
diagnostic and prognostic potential of the ratio of neutrophilic CD64 (nCD64) and
monocytic HLA-DR (mHLA-DR) median fluorescence index in monitoring of neonatal
sepsis. METHODS: Blood from 100 neonates suspected of sepsis and 29 healthy
controls was collected on clinical suspicion of sepsis, and the expression of
nCD64, mHLA-DR was evaluated by Flow Cytometry; thereby, a derived parameter
"Sepsis index," SI = nCD64/mHLA-DR * 100 was estimated. RESULTS: At day 1,
sensitivity and specificity to detect sepsis using nCD64 was 73.01% and 89.18%,
respectively, while for SI it was 73.01% and 72.22%, respectively. On Kaplan
Meier analysis, neonates with SI > cut-off showed a higher 30 day-mortality than
those with low SI (P = 0.096). On multivariate analysis, the factor associated
with mortality in our cohort was Apgar score <=3, while SI showed a trend toward
significance. CONCLUSIONS: At day1, nCD64 is useful for the diagnosis of neonatal
sepsis whereas mHLA-DR is beneficial for monitoring patients at a later time
point. The SI is a marker of moderate diagnostic sensitivity and supplements the
current arsenal of laboratory investigations to detect neonatal sepsis. As a
marker of prognosis, a high SI shows a trend towards greater mortality. (c) 2015
Clinical Cytometry Society.
PMID- 25850940
TI - Adiabaticity of the proton-coupled electron-transfer step in the reduction of
superoxide effected by nickel-containing superoxide dismutase metallopeptide
based mimics.
AB - Nickel-containing superoxide dismutases (NiSODs) are bacterial metalloenzymes
that catalyze the disproportionation of O2(-). These enzymes take advantage of a
redox-active nickel cofactor, which cycles between the Ni(II) and Ni(III)
oxidation states, to catalytically disprotorptionate O2(-). The Ni(II) center is
ligated in a square planar N2S2 coordination environment, which, upon oxidation
to Ni(III), becomes five-coordinate following the ligation of an axial imidazole
ligand. Previous studies have suggested that metallopeptide-based mimics of NiSOD
reduce O2(-) through a proton-coupled electron transfer (PCET) reaction with the
electron derived from a reduced Ni(II) center and the proton from a protonated,
coordinated Ni(II)-S(H(+))-Cys moiety. The current work focuses on the O2(-)
reduction half-reaction of the catalytic cycle. In this study we calculate the
vibronic coupling between the reactant and product diabatic surfaces using a
semiclassical formalism to determine if the PCET reaction is proceeding through
an adiabatic or nonadiabatic proton tunneling process. These results were then
used to calculate H/D kinetic isotope effects for the PCET process. We find that
as the axial imidazole ligand becomes more strongly associated with the Ni(II)
center during the PCET reaction, the reaction becomes more nonadiabatic. This is
reflected in the calculated H/D KIEs, which moderately increase as the reaction
becomes more nonadiabatic. Furthermore, the results suggest that as the axial
ligand becomes less Lewis basic the observed reaction rate constants for O2(-)
reduction should become faster because the reaction becomes more adiabatic. These
conclusions are in-line with experimental observations. The results thus indicate
that variations in the axial donor's ability to coordinate to the nickel center
of NiSOD metallopeptide-based mimics will strongly influence the fundamental
nature of the O2(-) reduction process.
PMID- 25850941
TI - The development and validation of new equations for estimating body fat
percentage among Chinese men and women.
AB - Equations based on simple anthropometric measurements to predict body fat
percentage (BF%) are lacking in Chinese population with increasing prevalence of
obesity and related abnormalities. We aimed to develop and validate BF% equations
in two independent population-based samples of Chinese men and women. The
equations were developed among 960 Chinese Hans living in Shanghai (age 46.2 (SD
5.3) years; 36.7% male) using a stepwise linear regression and were subsequently
validated in 1150 Shanghai residents (58.7 (SD 6.0) years; 41.7% male; 99%
Chinese Hans, 1% Chinese minorities). The associations of equation-derived BF%
with changes of 6-year cardiometabolic outcomes and incident type 2 diabetes
(T2D) were evaluated in a sub-cohort of 780 Chinese, compared with BF% measured
by dual-energy X-ray absorptiometry (DXA; BF%-DXA). Sex-specific equations were
established with age, BMI and waist circumference as independent variables. The
BF% calculated using new sex-specific equations (BF%-CSS) were in reasonable
agreement with BF%-DXA (mean difference: 0.08 (2 SD 6.64) %, P= 0.606 in men;
0.45 (2 SD 6.88) %, P< 0.001 in women). In multivariate-adjusted models, the BF%
CSS and BF%-DXA showed comparable associations with 6-year changes in TAG, HDL
cholesterol, diastolic blood pressure, C-reactive protein and uric acid (P for
comparisons >= 0.05). Meanwhile, the BF%-CSS and BF%-DXA had comparable areas
under the receiver operating characteristic curves for associations with incident
T2D (men P= 0.327; women P= 0.159). The BF% equations might be used as surrogates
for DXA to estimate BF% among adult Chinese. More studies are needed to evaluate
the application of our equations in different populations.
PMID- 25850942
TI - Molecular signature of erythroblast enucleation in human embryonic stem cells.
AB - While enucleation is a critical step in the terminal differentiation of human red
blood cells, the molecular mechanisms underlying this unique process remain
unclear. To investigate erythroblast enucleation, we studied the erythroid
differentiation of human embryonic stem cells (hESCs), which provide a unique
model for deeper understanding of the development and differentiation of multiple
cell types. First, using a two-step protocol, we demonstrated that terminal
erythroid differentiation from hESCs is directly dependent on the age of the
embryoid bodies. Second, by choosing hESCs in two extreme conditions of erythroid
culture, we obtained an original differentiation model which allows one to study
the mechanisms underlying the enucleation of erythroid cells by analyzing the
gene and miRNA (miR) expression profiles of cells from these two culture
conditions. Third, using an integrated analysis of mRNA and miR expression
profiles, we identified five miRs potentially involved in erythroblast
enucleation. Finally, by selective knockdown of these five miRs we found miR-30a
to be a regulator of erythroblast enucleation in hESCs.
PMID- 25850944
TI - 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of
Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care
(Endorsed by the American Heart Association, the Cardiological Society of India,
and Sociedad Latino Americana de Cardiologia Intervencionista; Affirmation of
Value by the Canadian Association of Interventional Cardiology-Association
Canadienne de Cardiologie d'intervention).
AB - This article provides a brief summary of the relevant recommendations and
references related to percutaneous mechanical circulatory support. The goal was
to provide the clinician with concise, evidence-based contemporary
recommendations, and the supporting documentation to encourage their application.
The full text includes disclosure of all relevant relationships with industry for
each writing committee member. A fundamental aspect of all expert consensus
statements is that these carefully developed, evidence-based documents can
neither encompass all clinical circumstances, nor replace the judgment of
individual physicians in management of each patient. The science of medicine is
rooted in evidence, and the art of medicine is based on the application of this
evidence to the individual patient. This expert consensus statement has adhered
to these principles for optimal management of patients requiring percutaneous
mechanical circulatory support.
PMID- 25850945
TI - Mitochondrial DNA Polymerase gamma Mutations and Their Implications in mtDNA
Alterations in Colorectal Cancer.
AB - Mitochondrial DNA was found to be highly mutated in colorectal cancer cells. One
of the key molecules involved in the maintenance of the mitochondrial genome is
the nuclear-encoded polymerase gamma. The aim of our study was to determine if
there is a link between polymorphisms within the polymerase gamma gene (POLG) and
somatic mutations within the mitochondrial genome in cancer cells. We
investigated POLG sequence variability in 50 colorectal cancer patients whose
complete mitochondrial genome sequences were determined. Relative mtDNA copy
number was also determined. We identified 251 sequence variants in the POLG gene.
Most of them were germline-specific (~92%). Twenty-one somatic changes in POLG
were found in 10 colorectal cancer patients. We have found no association between
the occurrence of mtDNA somatic mutations and the somatically occurring variants
in POLG. MtDNA content was reduced in patients carrying somatic variants in POLG
or germline nucleotide variants located in the region encoding the POLG
polymerase domain, but the difference did not reach statistical significance. Our
findings suggest that somatic mtDNA mutations occurring in colorectal cancer are
not a consequence of somatic mutations in POLG. Nevertheless, POLG nucleotide
variants may lead to a decrease in mtDNA content, and consequently result in
mitochondrial dysfunction.
PMID- 25850943
TI - Uncovering the genomic heterogeneity of multifocal breast cancer.
AB - Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral
lesions of invasive breast cancer, is relatively frequent and has been associated
with more aggressive features than unifocal cancer. Here, we aimed to investigate
the genomic heterogeneity between MFBC lesions sharing similar histopathological
parameters. Characterization of different lesions from 36 patients with ductal
MFBC involved the identification of non-silent coding mutations in 360 protein
coding genes (171 tumour and 36 matched normal samples). We selected only
patients with lesions presenting the same grade, ER, and HER2 status. Mutations
were classified as 'oncogenic' in the case of recurrent substitutions reported in
COSMIC or truncating mutations affecting tumour suppressor genes. All mutations
identified in a given patient were further interrogated in all samples from that
patient through deep resequencing using an orthogonal platform. Whole-genome
rearrangement screen was further conducted in 8/36 patients. Twenty-four patients
(67%) had substitutions/indels shared by all their lesions, of which 11 carried
the same mutations in all lesions, and 13 had lesions with both common and
private mutations. Three-quarters of those 24 patients shared oncogenic variants.
The remaining 12 patients (33%) did not share any substitution/indels, with inter
lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA,
TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further
apart in the mammary gland than homogeneous lesions. Genome-wide analyses of a
limited number of patients identified a common somatic background in all studied
MFBCs, including those with no mutation in common between the lesions. To
conclude, as the number of molecular targeted therapies increases and trials
driven by genomic screening are ongoing, our findings highlight the presence of
genomic inter-lesion heterogeneity in one-third, despite similar pathological
features. This implies that deeper molecular characterization of all MFBC lesions
is warranted for the adequate management of those cancers.
PMID- 25850946
TI - Temporal characterization of protein production levels from baculovirus vectors
coding for GFP and RFP genes under non-conventional promoter control.
AB - The ease of use and versatility of the Baculovirus Expression Vector System
(BEVS) has made it one of the most widely used systems for recombinant protein
production However, co-expression systems currently in use mainly make use of the
very strong very late p10 and polyhedron (polh) promoters to drive expression of
foreign genes, which does not provide much scope for tailoring expression ratios
within the cell. This work demonstrates the use of different Autographa
californica multicapsid nucleopolyhedrovirus (AcMNPV) promoters to control the
timing and expression of two easily traceable fluorescent proteins, the enhanced
green fluorescent protein (eGFP), and a red fluorescent protein (DsRed2) in a
BEVS co-expression system. Our results show that gene expression levels can
easily be controlled using this strategy, and also that modulating the expression
level of one protein can influence the level of expression of the other protein
within the system, thus confirming the concept of genes "competing" for limited
cellular resources. Plots of "expression ratios" of the two model genes over time
were obtained, and may be used in future work to tightly control timing and
levels of foreign gene expression in an insect cell co-expression system.
PMID- 25850947
TI - Novel detergent for whole organ tissue engineering.
AB - Whole organ tissue engineering for various organs, including the heart, lung,
liver, and kidney, has demonstrated promising results for end-stage organ
failure. However, the sodium dodecyl sulfate (SDS)-based protocol for standard
decellularization has drawbacks such as clot formation in vascularized
transplantation and poor cell engraftment in recellularization procedures.
Preservation of the surface milieu of extracellular matrices (ECMs) might be
crucial for organ generation based on decellularization/recellularization
engineering. We examined a novel detergent, sodium lauryl ether sulfate (SLES),
to determine whether it could overcome the drawbacks associated with SDS using
rat heart and kidney. Both organs were perfused in an antegrade fashion with
either SLES or SDS. Although immunohistochemistry for collagen I, IV, laminin,
and fibronectin showed similar preservation in both detergents, morphological
analysis using scanning electron microscopy and an assay of glycosaminoglycan
content on ECMs showed that SLES-treated tissues had better-preserved ECMs than
SDS-treated tissues. Mesenteric transplantation revealed SLES did not induce
significant inflammation, as opposed to SDS. Platelet adhesion to decellularized
tissues was significantly reduced with SLES. Overall, SLES could replace older
detergents such as SDS in the decellularization process for generation of
transplantable recellularized organs.
PMID- 25850948
TI - Lack of effect of sacral nerve stimulation for incontinence in patients with
systemic sclerosis.
AB - AIM: Systemic sclerosis (SSc) is a multisystem disorder of unknown aetiology
leading to the deposition of excessive connective tissue in the skin, blood
vessels and internal organs. Gastrointestinal involvement occurs in 90% of cases
and the prevalence of faecal incontinence (FI) is 38%. This study comprises the
largest case series assessing the efficacy of sacral nerve stimulation (SNS)
treatment for incontinence in this patient group. METHOD: A retrospective
analysis on prospectively collected data was performed on all SSc patients from
our two centres who had undergone SNS for FI. RESULTS: Ten female patients of
mean age of 54 (37-72) years had temporary SNS performed. The mean duration of FI
was 13 (2-25) years. All had passive FI. Each patient had preprocedure anorectal
physiology and endoanal ultrasound examinations documenting internal sphincter
atrophy/fragmentation or reduced anal resting pressure. Overall there was no
statistically significant difference (P = 0.57) in the total Wexner incontinence
scores before (mean 15.1 +/- 2.6 SD) and during temporary SNS procedures (mean
13.1 +/- 3.6 SD). Two patients with a significant improvement went on to have
permanent SNS with only one achieving a favourable outcome at 1 year. CONCLUSION:
This study showed that SNS failed to reduce episodes of leakage in nine out of 10
patients with systemic sclerosis affected with incontinence.
PMID- 25850949
TI - Microtensile bond strength of lithium disilicate to zirconia with the CAD-on
technique.
AB - PURPOSE: Recently, a novel technique was introduced to combine lithium disilicate
and zirconia into one restoration. The purpose of this study was to compare the
microtensile bond strength of veneering ceramic to a zirconia core in two
techniques: the e.max(r) CAD-on technique and the Press-on technique. MATERIALS
AND METHODS: Group A was prepared by veneering sintered zirconia blocks (e.max(r)
ZirCAD) with lithium disilicate blocks (e.max(r) CAD) using the CAD-on technique
according to manufacturer's instructions. Group B was prepared by taking sintered
e.max(r) ZirCAD blocks and veneering them with fluorapatite glass-ceramic
(e.max(r) ZirPress) using the Press-on technique according to manufacturer's
instructions. Each block was loaded in a dynamic cyclic loading machine. The
blocks were then sectioned into 1 * 1 mm(2) beams (n = 43) using a precision saw,
thermocycled, and loaded in tension until failure on a universal testing machine.
A mean and standard deviation were determined per group. Data were analyzed using
an unpaired t-test (alpha = 0.05). RESULTS: The mean microtensile bond strengths
were 44.0 +/- 13.8 MPa for the CAD-on technique and 14.9 +/- 8.8 MPa for the
Press-on technique. Significant differences were found between the two groups (p
= 2.7E-19). CONCLUSIONS: The CAD-on technique (lithium disilicate/zirconia)
resulted in greater microtensile bond strength than the Press-on technique
(fluorapatite glass-ceramic/zirconia).
PMID- 25850950
TI - Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric
Antigen Receptor-Modified T-cell Therapy for CEA+ Liver Metastases.
AB - PURPOSE: Chimeric antigen receptor-modified T cells (CAR-T) have demonstrated
encouraging results in early-phase clinical trials. Successful adaptation of CAR
T technology for CEA-expressing adenocarcinoma liver metastases, a major cause of
death in patients with gastrointestinal cancers, has yet to be achieved. We
sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous
hepatic artery infusions (HAIs). EXPERIMENTAL DESIGN: We conducted a phase I
trial to test HAI of CAR-T in patients with CEA(+) liver metastases. Six patients
completed the protocol, and 3 received anti-CEA CAR-T HAIs alone in dose
escalation fashion (10(8), 10(9), and 10(10) cells). We treated an additional 3
patients with the maximum planned CAR-T HAI dose (10(10) cells * 3) along with
systemic IL2 support. RESULTS: Four patients had more than 10 liver metastases,
and patients received a mean of 2.5 lines of conventional systemic therapy before
enrollment. No patient suffered a grade 3 or 4 adverse event related to the CAR-T
HAIs. One patient remains alive with stable disease at 23 months following CAR-T
HAI, and 5 patients died of progressive disease. Among the patients in the cohort
that received systemic IL2 support, CEA levels decreased 37% (range, 19%-48%)
from baseline. Biopsies demonstrated an increase in liver metastasis necrosis or
fibrosis in 4 of 6 patients. Elevated serum IFNgamma levels correlated with IL2
administration and CEA decreases. CONCLUSIONS: We have demonstrated the safety of
anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily
pretreated population with large tumor burdens. Further clinical testing of CAR-T
HAIs for liver metastases is warranted.
PMID- 25850952
TI - Accelerated whole-brain multi-parameter mapping using blind compressed sensing.
AB - PURPOSE: To introduce a blind compressed sensing (BCS) framework to accelerate
multi-parameter MR mapping, and demonstrate its feasibility in high-resolution,
whole-brain T1rho and T2 mapping. METHODS: BCS models the evolution of
magnetization at every pixel as a sparse linear combination of bases in a
dictionary. Unlike compressed sensing, the dictionary and the sparse coefficients
are jointly estimated from undersampled data. Large number of non-orthogonal
bases in BCS accounts for more complex signals than low rank representations. The
low degree of freedom of BCS, attributed to sparse coefficients, translates to
fewer artifacts at high acceleration factors (R). RESULTS: From 2D retrospective
undersampling experiments, the mean square errors in T1rho and T2 maps were
observed to be within 0.1% up to R = 10. BCS was observed to be more robust to
patient-specific motion as compared to other compressed sensing schemes and
resulted in minimal degradation of parameter maps in the presence of motion. Our
results suggested that BCS can provide an acceleration factor of 8 in prospective
3D imaging with reasonable reconstructions. CONCLUSION: BCS considerably reduces
scan time for multiparameter mapping of the whole brain with minimal artifacts,
and is more robust to motion-induced signal changes compared to current
compressed sensing and principal component analysis-based techniques.
PMID- 25850954
TI - Low-temperature liquid phase reduced TiO2 nanotube arrays: synergy of morphology
manipulation and oxygen vacancy doping for enhancement of field emission.
AB - The partially reduced TiO(2) nanotube arrays (TNAs) are prepared via an
uncomplicated and low-cost liquid phase reduction strategy using NaBH(4) as the
reducing agent. By controlling and adjusting the reduction temperatures from 30
to 90 degrees C, the reduction treatment can not only change their surface
morphology but also introduce oxygen vacancies into them, resulting in an
optimized morphology, elevated Fermi-level, reduced effective work function and
improved conductivity of the TNAs. Meanwhile, the thermal and long-term stability
of oxygen vacancy are also investigated, indicating that the oxygen vacancies
retain long-term stability from room temperature up to 150 degrees C. More
interesting, partially reduced TNAs show drastically enhanced field emission (FE)
performances including substantially decreased turn-on field from 18.86 to 1.53 V
MUm(-1), a high current density of 4.00 mA cm(-2) at 4.52 V MUm(-1), and an
excellent FE stability and repeatability. These very promising results are
attributed to the combination of the optimized morphology and introduced oxygen
vacancies, which can increase FE sites, reduce effective work function and
increase conductivity.
PMID- 25850953
TI - Aromatase expression is linked to estrogenic sensitivity of periurethral muscles
in female rabbits.
AB - Beyond its role in the conversion of androgens to estrogens, the expression of
aromatase could influence on the estrogenic signalling in targeted tissues.
Considering the well-defined biochemical and physiological differences between
the pubococcygeus (Pcm) and bulbospongiosus (Bsm) muscles in female rabbits, it
is presently hypothesized that the aromatase expression is differentially linked
to the estrogen sensitivity of each muscle. To this end, serum estradiol levels
and the aromatase expression, presence of ERalpha and ERbeta and morphometry were
evaluated in the Pcm and Bsm of female rabbits allocated in control,
ovariectomized (OVX) and OVX treated with estradiol benzoate (OVX + EB) groups.
Aromatase expression was high in the Pcm. Independently to serum estradiol,
ovariectomy increased aromatase expression in the Pcm while decreased it in the
Bsm. The EB treatment avoided the effect of ovariectomy only in the Pcm. The
number of immunoreactive nuclei anti-ERalpha and anti-ERbeta was high in the Pcm
of OVX and OVX + EB rabbits, while those in the Bsm remained unchanged. The
number of peripheral nuclei per fibre and the cross-sectional area-to-myonucleus
ratio were modified only in the Pcm. Our findings support aromatase expression in
the Pcm, and Bsm of rabbits is differentially linked to estrogenic sensitivity of
each muscle.
PMID- 25850955
TI - Rapid and simple preparation of thiol-ene emulsion-templated monoliths and their
application as enzymatic microreactors.
AB - A novel, rapid and simple method for the preparation of emulsion-templated
monoliths in microfluidic channels based on thiol-ene chemistry is presented. The
method allows monolith synthesis and anchoring inside thiol-ene microchannels in
a single photoinitiated step. Characterization by scanning electron microscopy
showed that the methanol-based emulsion templating process resulted in a network
of highly interconnected and regular thiol-ene beads anchored solidly inside
thiol-ene microchannels. Surface area measurements indicate that the monoliths
are macroporous, with no or little micro- or mesopores. As a demonstration,
galactose oxidase and peptide-N-glycosidase F (PNGase F) were immobilized at the
surface of the synthesized thiol-ene monoliths via two different mechanisms.
First, cysteine groups on the protein surface were used for reversible covalent
linkage to free thiol functional groups on the monoliths. Second, covalent
linkage was achieved via free primary amino groups on the protein surface by
means of thiol-ene click chemistry and l-ascorbic acid linkage. Thus prepared
galactose oxidase and PNGase F microreactors demonstrated good enzymatic activity
in a galactose assay and the deglycosilation of ribonuclease B, respectively.
PMID- 25850956
TI - Oromandibular dystonia: a serious side effect of capecitabine.
AB - BACKGROUND: Capecitabine has activity against several types of cancer. In 10-15%
of patients treated with capecitabine, treatment is discontinued because of
serious adverse reactions, mostly within the first weeks of treatment. CASE
PRESENTATION: A 56 year-old female patient presented at the emergency department
after ten days of chemotherapy with progressive airway obstruction and complaints
of numbness of the tongue. She also had difficulty swallowing and was unable to
speak. Laboratory findings were completely normal and no co-medication was used,
in particular no dopamine antagonists. CONCLUSION: The case highlights the need
for awareness that capecitabine may potentially lead to severe life-threatening
complaints of oromandibular dystonia. We hypothesize that capecitabine passed the
blood brain barrier which led to a disruption within the basal ganglia in this
case. Prompt treatment with an anticholinergic drug and cessation of capecitabine
in the patient case led to disappearance of complaints.
PMID- 25850957
TI - The effect of LKB1 on the PI3K/Akt pathway activation in association with PTEN
and PIK3CA in HNC.
AB - OBJECTIVE: PI3K/Akt signalling pathway is frequently activated in several types
of cancer. However, activator molecules have not been analysed systematically in
HNSCC. The aim of this study was to investigate upstream activators and
inhibitors of this pathway. DESIGN: Prospective study. SETTING: University
hospital. PARTICIPANTS: 108 patients with HNC who were operated at the Istanbul
University, Cerrahpasa Medical Faculty, Department of Otorhinolaryngology.
METHODS: Mutations in the coding exons and the flanking intronic sequences of the
PIK3CA, PIK3R1 and AKT1 genes were analysed by direct sequencing. Expression
levels in the tumours and non-cancerous tissue samples were analysed by
quantitative RT-PCR, and Western blotting was performed to determine the
phosphorylation levels of the Akt1 protein. RESULTS: Two synonymous alterations
in exon 20 of the PIK3CA gene, a 6-bp duplication in the coding region of the
PIK3R1 and two different alterations in the non-coding regions of the AKT1 and
PIK3R1 genes were observed. Significant downregulation of LKB1 and PTEN mRNA
expression levels were detected in tumour tissues compared to non-cancerous
tissues. However, we did not observe any difference between the PIK3CA and AKT1
mRNA expression levels in the tumours and non-cancerous tissue samples. Akt1
phosphorylation was increased in 53.57% of the patients. CONCLUSIONS: Our results
indicate that the PI3K pathway has an important function in HNSCC progression
with the contribution of more than one gene of this pathway. Our data suggest
that in a high number of HNSCC tumours, PI3K/Akt signalling is activated by
different molecules or by the combination of these molecules.
PMID- 25850958
TI - Diagnostic algorithms in Charcot-Marie-Tooth neuropathies: experiences from a
German genetic laboratory on the basis of 1206 index patients.
AB - We present clinical features and genetic results of 1206 index patients and 124
affected relatives who were referred for genetic testing of Charcot-Marie-Tooth
(CMT) neuropathy at the laboratory in Aachen between 2001 and 2012. Genetic
detection rates were 56% in demyelinating CMT (71% of autosomal dominant (AD)
CMT1/CMTX), and 17% in axonal CMT (24% of AD CMT2/CMTX). Three genetic defects
(PMP22 duplication/deletion, GJB1/Cx32 or MPZ/P0 mutation) were responsible for
89.3% of demyelinating CMT index patients in whom a genetic diagnosis was
achieved, and the diagnostic yield of the three main genetic defects in axonal
CMT (GJB1/Cx32, MFN2, MPZ/P0 mutations) was 84.2%. De novo mutations were
detected in 1.3% of PMP22 duplication, 25% of MPZ/P0, and none in GJB1/Cx32.
Motor nerve conduction velocity was uniformly <38 m/s in median or ulnar nerves
in PMP22 duplication, >40 m/s in MFN2, and more variable in GJB1/Cx32, MPZ/P0
mutations. Patients with CMT2A showed a broad clinical severity regardless of the
type or position of the MFN2 mutation. Out of 75 patients, 8 patients (11%) with
PMP22 deletions were categorized as CMT1 or CMT2. Diagnostic algorithms are still
useful for cost-efficient mutation detection and for the interpretation of large
scale genetic data made available by next generation sequencing strategies.
PMID- 25850959
TI - A Conjugate Class of Utility Functions for Sequential Decision Problems.
AB - The use of the conjugacy property for members of the exponential family of
distributions is commonplace within Bayesian statistical analysis, allowing for
tractable and simple solutions to problems of inference. However, despite a
shared motivation, there has been little previous development of a similar
property for using utility functions within a Bayesian decision analysis. As
such, this article explores a class of utility functions that appear to be
reasonable for modeling the preferences of a decisionmaker in many real-life
situations, but that also permit a tractable and simple analysis within
sequential decision problems.
PMID- 25850960
TI - Openness and honesty in gaining fully informed consent will benefit both patients
and doctors.
PMID- 25850961
TI - Temporal dynamics of neural activity in motor execution and inhibition
processing.
AB - Although many neuroimaging studies using functional magnetic resonance imaging
have shown the neuronal networks for motor execution and inhibition processing,
the precise activation timing of each brain region is not yet well understood. In
the present study, we investigated the temporal dynamics of neural activities in
multiple brain regions using magnetoencephalography (MEG) and
electroencephalography (EEG) simultaneously during somatosensory Go/No-go
paradigms. The results of MEG showed that neural activities in the bilateral
premotor area at approximately 150 ms and in the primary motor cortex at
approximately 250 ms were only detected in Go trials, while brain responses in
the bilateral prefrontal cortex at approximately 170 ms were only observed in No
go trials. In addition, the amplitudes of the N140 and P300 components in EEG was
significantly larger in No-go trials than in Go trials, and the latencies of N140
and P300 were significantly later in No-go trials than in Go trials. Our results
indicated the time courses of neural processing in response execution and
inhibition processing, and revealed differences in their underlying neural
mechanisms.
PMID- 25850962
TI - Evaluation of stone-free rate using Guy's Stone Score and assessment of
complications using modified Clavien grading system for percutaneous nephro
lithotomy.
AB - To prospectively evaluate the ability of Guy's Stone Score (GSS) in predicting
stone clearance rate and complication rate (by modified Clavien grade) for renal
stones treated by percutaneous nephrolithotomy (PNL). From January 2013 to June
2014, a total of 142 patients undergoing PNL were evaluated prospectively.
Patients with co-morbidities like hypertension, diabetes, renal failure were
excluded from the study. All patients were classified according to GSS based on
the findings of pre-operative intravenous urography (IVU) and per-operative
retrograde pyelography (RGP). All PNL procedures were done by standard technique
in prone position and success was defined as no residual stone visible on X-ray
KUB done on the third postoperative day. Complications were classified according
to modified Clavien grading system. The initial stone clearance rate was 71.1%
and overall final stone clearance rate was 90.14%. The complication rate
according to Clavien grading system was 40.1%. The final stone clearance rates
were 93.9, 85.71, 90.47, and 77.77% in GSS I, II, III, and IV, respectively
(p<0.001, <0.05, <0.05 and >0.05, respectively). The Clavien complication rates
were 23, 61, 52, and 77.7% in GSS I, II, III, and IV, respectively (p<0.001). The
GSS is a simple and easily reproducible system to preoperatively predict stone
free rate and perioperative complication rate. It helps in better patient
counseling preoperatively.
PMID- 25850963
TI - Facile Self-Assembly of Metallo-Supramolecular Ring-in-Ring and Spiderweb
Structures Using Multivalent Terpyridine Ligands.
AB - A series of metallo-supramolecular ring-in-ring structures was generated by
assembling Cd(II) ions and the multivalent terpyridine ligands (L(1-3)) composed
of one 60 degrees -bent and two 120 degrees -bent bis(terpyridine)s with varying
alkyl linker lengths. The mechanistic study for the self-assembly process
excluded an entropically templated pathway and showed that the intramolecularly
complexed species is the key intermediate leading to ring-in-ring formation. The
next-generation superstructure, a spiderweb, was produced in quantitative yield
using the elongated decakis(terpyridine) ligand (L(5)).
PMID- 25850964
TI - Genetic variants within the TNFRSF1B gene and susceptibility to rheumatoid
arthritis and response to anti-TNF drugs: a multicenter study.
AB - BACKGROUND: Recent research suggests that genetic variants in the tumor necrosis
factor receptor 2 (TNFRSF1B) gene may have an impact on susceptibility to
rheumatoid arthritis (RA) and drug response. The present population-based case
control study was carried out to evaluate whether 5 tagging single-nucleotide
polymorphisms (SNPs) within the TNFRSF1B gene are associated with the risk of RA
and response to antitumor necrosis factor (TNF) drugs. METHODS: The study
population included 1412 RA patients and 1225 healthy controls. A subset of 596
anti-TNF-naive RA patients was selected to assess the association of TNFRSF1B
SNPs and drug response according to the EULAR response criteria. RESULTS: We
found that carriers of the TNFRSF1Brs3397C allele had a significantly increased
risk of developing RA (P=0.0006). Importantly, this association remained
significant after correction for multiple testing. We also confirmed the lack of
association of the TNFRSF1Brs1061622 SNP with the risk of RA in the single-SNP
analysis (P=0.89), but also through well-powered meta-analyses (PDOM=0.67 and
PREC=0.37, respectively). In addition, our study showed that carriers of the
TNFRSF1Brs3397C/C, TNFRSF1Brs1061622G/G, and TNFRSF1Brs1061631A/A genotypes had
an increased risk of having a worse response to anti-TNF drugs at the level of P
less than 0.05 (P=0.014, 0.0085 and 0.028, respectively). We also observed that,
according to a log-additive model, carriers of the TNFRSF1Brs3397C or
TNFRSF1Brs1061622G alleles showed an increased risk of having worse response to
anti-TNF medications (P=0.018 and 0.0059). However, the association of the
TNFRSF1Brs1061622 SNP only reached marginal significance after correction for
multiple testing according to a log-additive model (P=0.0059) and it was not
confirmed through a meta-analysis (PDOM=0.12). CONCLUSION: Our results suggest
that the TNFRSF1Brs3397 variant may play a role in modulating the risk of RA, but
does not provide strong evidence of an impact of TNFRSF1B variants in determining
response to anti-TNF drugs.
PMID- 25850965
TI - Lethal toxicity after administration of azacytidine: implication of the cytidine
deaminase-deficiency syndrome.
AB - Azacytidine, an antimetabolite with an original epigenetic mechanism of action,
increases survival in patients diagnosed with high-risk myelodysplasic syndromes
or acute myeloid leukemia with less than 30% medullar blasts. Azacytidine is a
pyrimidine derivative that undergoes metabolic detoxification driven by cytidine
deaminase (CDA), a liver enzyme whose gene is prone to genetic polymorphism,
leading to erratic activity among patients. Clinical reports have shown that
patients with the poor metabolizer (PM) phenotype are likely to experience early
severe or lethal toxicities when treated with nucleosidic analogs such as
gemcitabine or cytarabine. No clinical data have been available thus far on the
relationships between CDA PM status and toxicities in azacytidine-treated
patients. Here, we measured CDA activity in a case of severe toxicities with
fatal outcome in a patient undergoing standard azacytidine treatment. Results
showed that the patient was PM (i.e. residual activity reduced by 63%), thus
suggesting that an impaired detoxification step could have given rise to the
lethal toxicities observed. This case report calls for further prospective
studies investigating the exact role that CDA status plays in the clinical
outcome of patients treated with azacytidine.
PMID- 25850967
TI - An empirical investigation of suicide schemas in individuals with Posttraumatic
Stress Disorder.
AB - Posttraumatic Stress Disorder (PTSD) has been strongly associated with
suicidality. Despite the growing evidence suggesting that suicidality is
heightened by the presence of an elaborated suicide schema, investigations of
suicide schemas are sparse. Using novel methodologies, this study aimed to
compare the suicide schema of PTSD individuals with and without suicidal ideation
in the past year. Fifty-six participants with a diagnosis of PTSD (confirmed via
the Clinician Administered PTSD Scale) completed questionnaires to assess
suicidality, depressive severity and hopelessness. A series of direct and
indirect cognitive tasks were used to assess suicide schemas. The pathfinder
technique was employed to construct graphical representations of the groups'
suicide schemas. The suicidal group reported significantly more severe PTSD
symptoms, depressive symptoms, hopelessness and suicidality. The suicide schema
of the suicidal group was significantly more extensive compared to the non
suicidal group even after taking into account in the analyses group differences
in clinical measures. Moreover, the suicide schemas of the two groups were
qualitatively distinct from each other. These findings provide support for
contemporary theories of suicide which view suicide schemas as an important
indicator of suicide risk. The investigation of schema constructs opens a new
avenue of research for understanding suicide.
PMID- 25850966
TI - Genetic variation of the dopamine transporter (DAT1) influences the acute
subjective responses to cocaine in volunteers with cocaine use disorders.
AB - OBJECTIVE: The aim of this study was to identify gene variants of DAT1 (SLC6A3)
that modulate subjective responses to acute cocaine exposure. METHODS: Non
treatment-seeking volunteers (n=66) with cocaine use disorders received a single
bolus infusion of saline and cocaine (40 mg, intravenous) in a randomized order.
Subjective effects were assessed with visual analog scales administered before (
15 min) and up to 20 min after infusion. Ratings of subjective effects were
normalized to baseline, and saline infusion values were subtracted. Data were
analyzed using repeated measures analysis of variance. DNA from the participants
was genotyped for the DAT1 intron 8 (rs3836790) and 3'-untranslated region
(rs28363170) variable number of tandem repeats. RESULTS: Participants were mostly
male (~80%) and African American (~70%). No differences were found among drug use
variables between groups for either polymorphism. Carriers of the 9-allele of the
DAT1 3'-untranslated region (9,9 and 9,10) exhibited greater responses to cocaine
for 'high', 'any drug effect', 'anxious', and 'stimulated' (all P-values<0.001)
compared with individuals homozygous for the 10-allele. For the intron 8
polymorphism, individuals homozygous for the 6-allele exhibited greater responses
for 'anxious' compared with carriers of the 5-allele (P<0.001). Individuals
possessing the genotype pattern of 10,10 and at least one 5-allele reported lower
responses to 'good effects', 'bad effects', 'depressed', and 'anxious' (all P
values<0.01). CONCLUSION: The data presented here show for the first time support
for the hypothesis that genetic differences in DAT1 contribute to the variation
in subjective responses to cocaine among participants with cocaine use disorders.
PMID- 25850968
TI - Long-term efficacy of sitagliptin as either monotherapy or add-on therapy to
metformin: improvement in glycemic control over 2 years in patients with type 2
diabetes.
AB - OBJECTIVE: To evaluate the efficacy of once daily sitagliptin 100 mg as
monotherapy or as add-on to metformin in patients with type 2 diabetes mellitus
(T2DM) over 2 years of treatment. RESEARCH DESIGN AND METHODS: The monotherapy
analysis used pooled 104 week data from 64 patients in two randomized, double
blind trials evaluating the safety and efficacy of sitagliptin monotherapy. Data
used were from patients who were randomized to sitagliptin 100 mg/day, were not
on an antihyperglycemic agent at the screening visit, had baseline A1C of 7.0%
10.0%, and had Week 104 A1C measurements. The add-on to metformin analysis used
pooled data from 347 patients in two randomized double-blind trials evaluating
the safety and efficacy of sitagliptin + metformin combination therapy. Data used
were from patients who were randomized to sitagliptin 100 mg/day + metformin
>=1500 mg/day, had baseline A1C of 7%-10%, and had Week 104 A1C measurements.
Excluded from either analysis were patients who discontinued prior to 2 years
(e.g., due to lack of efficacy, a need for rescue medications, or adverse
experiences). Analysis endpoints were A1C, fasting plasma glucose (FPG), HOMA
beta, proinsulin/insulin (P/I) ratio, and for monotherapy, 2 hour post-meal
plasma glucose (PMG). RESULTS: For the pooled monotherapy cohort, after 2 years
of treatment, mean A1C, FPG, and 2 hour PMG decreased from baseline values of
7.9%, 156 mg/dL, and 223 mg/dL to 6.9%, 143 mg/dL, and 191 mg/dL, respectively,
while HOMA-beta increased from 67% to 85% and P/I ratio improved from 0.57 to
0.28. For the pooled add-on to metformin cohort, after 2 years of treatment, mean
A1C and FPG decreased from baseline values of 7.7% and 160 mg/dL to 6.9% and 140
mg/dL, respectively, while HOMA-beta increased from 50% to 62% and P/I ratio
improved from 0.33 to 0.28. These analyses are limited in that only patients who
were able to complete 104 weeks of study were included. CONCLUSION: In the subset
of patients with T2DM who maintained and completed treatment for 2 years with
sitagliptin as monotherapy or as add-on to metformin, improvements in glycemic
control and measures of beta-cell function were observed over the course of
treatment.
PMID- 25850969
TI - Controlled reactivity tuning of metal-functionalized vanadium oxide clusters.
AB - Controlling the assembly and functionalization of molecular metal oxides [Mx Oy
](n-) (M=Mo, W, V) allows the targeted design of functional molecular materials.
While general methods exist that enable the predetermined functionalization of
tungstates and molybdates, no such routes are available for molecular vanadium
oxides. Controlled design of polyoxovanadates, however, would provide highly
active materials for energy conversion, (photo-) catalysis, molecular magnetism,
and materials science. To this end, a new approach has been developed that allows
the reactivity tuning of vanadium oxide clusters by selective metal
functionalization. Organic, hydrogen-bonding cations, for example,
dimethylammonium are used as molecular placeholders to block metal binding sites
within vanadate cluster shells. Stepwise replacement of the placeholder cations
with reactive metal cations gives mono- and difunctionalized clusters. Initial
reactivity studies illustrate the tunability of the magnetic, redox, and
catalytic activity.
PMID- 25850970
TI - Analysis of 24-Hour IOP-related Pattern Changes After Medical Therapy.
PMID- 25850971
TI - Estimated intakes of brominated flame retardants via diet and dust compared to
internal concentrations in a Swedish mother-toddler cohort.
AB - Tri-decabrominated diphenyl ethers (tri-decaBDEs), isomer-specific
hexabromocyclododecanes (HBCDs) and 14 emerging brominated flame retardants
(EBFRs) were determined in Swedish market basket samples, two pooled breast milk
samples and house dust collected in homes of first-time mothers. Daily dietary
and dust intakes were estimated for the mothers and their toddlers and compared
to previously reported levels in serum of both the mothers and toddlers and in
feces of the toddlers (n=20). Diet was the main contributor for intake of
SigmapentaBDE and alpha-tetrabromoethylcyclohexane (DBE-DBCH) for both mothers
and toddlers. For SigmaoctaBDE, SigmaHBCD and pentabromobenzene (PBBz), dietary
intake was more important for mothers while house dust ingestion was more
important for toddlers. House dust was the main exposure route for SigmadecaBDE,
decabromodiphenyl ethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH
TBB), bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), bis(2,4,6-tribromophenoxy)
ethane (BTBPE) and pentabromotoluene (PBT) for both mothers and toddlers.
Significant correlations (Spearmans, alpha<0.05) were found between the mothers'
BDE serum concentrations and their consumption of meat and fish while no
correlations were found between BFR dietary intake and serum or feces
concentrations in toddlers. Octa-decaBDE congener concentrations in serum and
feces of toddlers were significantly correlated to those in house dust. BDE-207
and -208 concentrations in serum of mothers were significantly correlated with
the nonaBDEs in house dust. The correlations between house dust and internal
concentrations and comparison of the house dust and dietary contributions to the
estimated daily intakes suggest that dust exposure plays a larger role for the
octa-decaBDE body burden in toddlers than in their mothers.
PMID- 25850972
TI - Repeatability, ephemerality and inconvenient truths in the speciation process.
AB - Everyone appreciates the happy fiction that species conform to the simple
theoretical convenience of a single panmictic population. In speciation genetics,
a further standard simplification is that it is only those genetic differences
that are fixed between diverging populations that need concern us in order to
understand the accumulation of intrinsic barriers to reproduction. To a first
approximation, of course, both of these assumptions are appropriate and theory
based on them provides compelling insights into diverse evolutionary phenomena
(Orr & Turelli ). But what else can we learn about the begetting of biodiversity,
speciation, by considering explicitly some less convenient realities of natural
populations? Specifically, how does genetic variation at incompatibility loci
within a species influence interspecies hybridization upon secondary contact?
And, in nature, how repeatable among distinct bouts of secondary contact are the
genomic outcomes of hybridization? Mandeville et al. () tackle exactly this
question in their new study in Molecular Ecology on five species of suckers, fish
of the genus Catostomus, that overlap sympatrically in different portions of
their subdivided ranges that occupy different rivers. They document substantial
genomic heterogeneity in realized hybridization in nature, both among species
pairs and among the source populations for hybrids of a given species pair. This
imperfect repeatability of episodes of hybridization implies greater permeability
of species barriers in some parts of their range, with intriguing consequences
for how the integrity of species as independently evolving units could be
susceptible to collapse.
PMID- 25850973
TI - Arrow physicians: are economics and medicine philosophically incompatible?
AB - Economics is en route to its further expansion in medicine, but many in the
medical community remain unconvinced that its impact will be positive. Thus, a
philosophical enquiry into the compatibility of economics and medicine is
necessary to resolve the disagreements. The fundamental mission of medicine
obliges physicians to practise science and compassion to serve the patient's best
interests. Conventional (neoclassical) economics assumes that individuals are
self-interested and that competitive markets will emerge optimal states.
Economics is seemingly incompatible with the emphasis of putting patients'
interests first. This idea is refuted by Professor Kenneth Arrow's health
economics seminal paper. Arrow emphasizes that medical practice involves agency,
knowledge, trust and professionalism, and physician-patient relation critically
affects care quality. The term Arrow Physician is used to mean a humanistic carer
who has a concern for the patient and acts on the best available evidence with
health equity in mind. To make this practice sustainable, implementing
appropriate motivations, constitutions and institutions to enable altruistic
agency is critical. There is substantial evidence that polycentric governance can
encourage building trust and reciprocity, so as to avoid depletion of communal
resources. This paper proposes building trusting institutions through granting
altruistic physicians adequate autonomy to direct resources based on patients'
technical needs. It also summarizes the philosophy bases of medicine and
economics. It, therefore, contributes to developing a shared language to
facilitate intellectual dialogues, and will encourage trans-disciplinary research
into medical practice. This should lead to medicine being reoriented to care for
whole persons again.
PMID- 25850974
TI - Environmental factors contribute to the formation and maintenance of the contact
zone observed in deciduous broad-leaved tree species in Japan.
AB - Contact zones are defined as areas where populations from different refugia meet
during a postglacial expansion and distinct DNA lineages are mixedly distributed.
In Japan, contact zones of various plants and animals were reported from the
Kinki-Chugoku region. These contact zones appear to be maintained without any
drastic topographic barriers such as those observed in the Alps and Pyrenees
Mountains. In this study, the mechanisms underlying the formation and/or
maintenance of these contact zones were investigated using six deciduous broad
leaved tree species (Carpinus laxiflora, C. tschonoskii, C. japonica, Magnolia
obovata, Padus grayana, and Euonymus oxyphyllus). First, the precise location of
the contact zones was examined by intensive genetic analysis of the six species.
Second, the relationships between the geographic location of the contact zone and
various environmental factors, including climate and topography, were
investigated by generalized additive models to reveal the mechanisms of the
formation and maintenance of the contact zones. As a result, four of the six
examined plant species clearly showed a geographically common contact zone in
Hyogo Prefecture and its adjacent areas. The results of the generalized additive
models indicate that the pattern of low habitat suitability estimated by
ecological niche modeling was the most important factor for determining the
location of the common contact zone. These results suggest that areas with low
habitat suitability in Hyogo Prefecture restrict the migration and gene flow of
the four species in this region, and thus, they maintain the pattern of the
contact zones. This study suggests that there are major effects of habitat
suitability on the formation and maintenance of the contact zones.
PMID- 25850975
TI - The effects of statins on benign prostatic hyperplasia in elderly patients with
metabolic syndrome.
AB - PURPOSE: To evaluate the effects of simvastatin and atorvastatin in elderly male
patients with benign prostatic hyperplasia (BPH) accompanied by metabolic
syndrome (MetS). METHODS: Eligible patients aged >60 year with BPH accompanied by
MetS were randomly assigned to receive 40 mg of simvastatin daily, 20 mg of
atorvastatin daily or placebo (control group) treatment for 12 months. Serum
lipids, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP),
prostate-specific antigen, prostate volume (PV) and the International Prostate
Symptom Score (IPSS) were tested before and after treatment. RESULTS: The levels
of serum total cholesterol (TC), triglycerides, low-density lipoprotein
cholesterol, hs-CRP, IL-6 and IPSS was decreased, serum high-density lipoprotein
cholesterol (HDL-C) was increased, and PV was reduced in the patients following
treatments with statins. The PV of the patients who received simvastatin were
reduced more than those of the patients who received atorvastatin. The decrease
in PV was more significant in the obesity patients than in the normal weight
patients and in the hyperlipidemia patients than in the normal-lipid patients
following the statin interventions. The reduction in PV was positively related to
the decreases in the levels of TC and IL-6 and to the increase in the level of
HDL-C. CONCLUSIONS: Simvastatin and atorvastatin significantly reduced PV,
improved lower urinary tract symptoms, and slowed the clinical progression of BPH
possibly by lowering cholesterol and anti-inflammatory factors.
PMID- 25850976
TI - Depression and cardiovascular disease.
AB - There is a wealth of evidence linking depression to increased risk for
cardiovascular disease (CVD) and worse outcomes among patients with known CVD. In
addition, there are safe and effective treatments for depression. Despite this,
depression remains under-recognized and undertreated in patients at risk for or
living with CVD. In this review, we first summarize the evidence linking
depression to increased risk of CVD and worse patient outcomes. We then review
the mechanisms by which depression may contribute to cardiovascular risk and poor
cardiovascular outcomes. We then summarize prior studies of depression treatment
on cardiovascular outcomes. Finally, we offer guidance in the identification and
management of depression among CVD populations. Given that 1 in 4 CVD patients
has concurrent depression, application of these best-practices will assist
providers in achieving optimal outcomes for their CVD patients.
PMID- 25850977
TI - Determining pathogenicity in cardiac genetic testing: Filling in the blank
spaces.
PMID- 25850978
TI - Recent findings of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs) on
atherosclerosis and coronary heart disease (CHD) contrasting studies in Western
countries to Japan.
AB - Recent long-term randomized clinical trials (RCTs) of long-chain n-3
polyunsaturated fatty acids (LCn-3 PUFAs) on coronary heart disease (CHD) among
high-risk patients conducted in Western countries all failed to show their
clinical benefits. In striking contrast, an RCT of LCn-3 PUFAs on CHD conducted
in Japan, which is a combination of secondary and primary prevention, showed a
significant 19% reduction. Potential reasons for this discrepancy are large
differences in doses of LCn-3 PUFAs administered (300-900 mg/day in Western
countries vs. 1800 mg/day in Japan) and background dietary intake of LCn-3 PUFAs
(<300 mg/day in Western countries vs. >1000 mg/day in Japan). These observations
suggest that higher doses of LCn-3 PUFAs than examined in RCTs in Western
countries may be cardio-protective. Atherosclerosis is the major underlying cause
of CHD. Recent observational studies and an RCT of LCn-3 PUFAs on atherosclerosis
in Japan show that LCn-3 PUFAs are anti-atherogenic. In this brief review, we
focus on recent epidemiological and clinical findings of LCn-3 PUFAs on
atherosclerosis and CHD, contrasting studies in Western countries to those in
Japan. We also discuss mechanisms of high-dose LCn-3 PUFAs on atherosclerosis.
PMID- 25850979
TI - Biological pacemakers: Ready for the clinic?
PMID- 25850980
TI - Fast GPU-based computation of spatial multigrid multiframe LMEM for PET.
AB - Significant efforts were invested during the last decade to accelerate PET list
mode reconstructions, notably with GPU devices. However, the computation time per
event is still relatively long, and the list-mode efficiency on the GPU is well
below the histogram-mode efficiency. Since list-mode data are not arranged in any
regular pattern, costly accesses to the GPU global memory can hardly be optimized
and geometrical symmetries cannot be used. To overcome obstacles that limit the
acceleration of reconstruction from list-mode on the GPU, a multigrid and
multiframe approach of an expectation-maximization algorithm was developed. The
reconstruction process is started during data acquisition, and calculations are
executed concurrently on the GPU and the CPU, while the system matrix is computed
on-the-fly. A new convergence criterion also was introduced, which is
computationally more efficient on the GPU. The implementation was tested on a
Tesla C2050 GPU device for a Gemini GXL PET system geometry. The results show
that the proposed algorithm (multigrid and multiframe list-mode expectation
maximization, MGMF-LMEM) converges to the same solution as the LMEM algorithm
more than three times faster. The execution time of the MGMF-LMEM algorithm was
1.1 s per million of events on the Tesla C2050 hardware used, for a reconstructed
space of 188 x 188 x 57 voxels of 2 x 2 x 3.15 mm3. For 17- and 22-mm simulated
hot lesions, the MGMF-LMEM algorithm led on the first iteration to contrast
recovery coefficients (CRC) of more than 75 % of the maximum CRC while achieving
a minimum in the relative mean square error. Therefore, the MGMF-LMEM algorithm
can be used as a one-pass method to perform real-time reconstructions for low
count acquisitions, as in list-mode gated studies. The computation time for one
iteration and 60 millions of events was approximately 66 s.
PMID- 25850981
TI - Multi-patient finite element simulation of keeled versus pegged glenoid implant
designs in shoulder arthroplasty.
AB - This study investigates the mechanical behaviour of keeled and pegged implant
designs used in shoulder arthroplasty for the first time using multiple 3D
models. Thus, this study should provide valuable insights into the preferable use
of either of these two controversial implant designs. Three-dimensional models of
a scapula were derived from the CT scans of five patients, and an inter-patient
specific finite element analysis with special attention to bone density and
boundary conditions was carried out. A distinct decrease in the investigated
parameters was evident with the pegged implant in all of the patients,
specifically for the implant and the bone cement. The relevance of the stress
reduction within the bone is minor, whereas the reduction in the stress of the
bone cement contributes to an increase in the bone cement survival. The
particular construction of the pegged implant provides better stability and
therefore supports bone ingrowth. The large variations between the patients show
the necessity of patient-specific simulations and the use of multiple models to
derive valuable results. In the conducted inter-patient-specific FEA, the pegged
glenoid implants were found to exhibit superior behaviour compared with keeled
implants. The results confirm the general clinical findings and demonstrate the
FEA as a valuable tool in prosthetic and orthopaedic problems.
PMID- 25850982
TI - Continuous-wavelet-transform analysis of the multifocal ERG waveform in glaucoma
diagnosis.
AB - The vast majority of multifocal electroretinogram (mfERG) signal analyses to
detect glaucoma study the signals' amplitudes and latencies. The purpose of this
paper is to investigate application of wavelet analysis of mfERG signals in
diagnosis of glaucoma. This analysis method applies the continuous wavelet
transform (CWT) to the signals, using the real Morlet wavelet. CWT coefficients
resulting from the scale of maximum correlation are used as inputs to a neural
network, which acts as a classifier. mfERG recordings are taken from the eyes of
47 subjects diagnosed with chronic open-angle glaucoma and from those of 24
healthy subjects. The high sensitivity in the classification (0.894) provides
reliable detection of glaucomatous sectors, while the specificity achieved
(0.844) reflects accurate detection of healthy sectors. The results obtained in
this paper improve on the previous findings reported by the authors using the
same visual stimuli and database.
PMID- 25850983
TI - Strength analysis of clavicle fracture fixation devices and fixation techniques
using finite element analysis with musculoskeletal force input.
AB - In the cases, when clavicle fractures are treated with a fixation plate, opinions
are divided about the best position of the plate, type of plate and type of screw
units. Results from biomechanical studies of clavicle fixation devices are
contradictory, probably partly because of simplified and varying load cases used
in different studies. The anatomy of the shoulder region is complex, which makes
it difficult and expensive to perform realistic experimental tests; hence,
reliable simulation is an important complement to experimental tests. In this
study, a method for finite element simulations of stresses in the clavicle plate
and bone is used, in which muscle and ligament force data are imported from a
multibody musculoskeletal model. The stress distribution in two different
commercial plates, superior and anterior plating position and fixation including
using a lag screw in the fracture gap or not, was compared. Looking at the
clavicle fixation from a mechanical point of view, the results indicate that it
is a major benefit to use a lag screw to fixate the fracture. The anterior
plating position resulted in lower stresses in the plate, and the anatomically
shaped plate is more stress resistant and stable than a regular reconstruction
plate.
PMID- 25850984
TI - Stress distribution in a premolar 3D model with anisotropic and isotropic enamel.
AB - The aim of this study was to compare the areas of stress concentration in a three
dimensional (3D) premolar tooth model with anisotropic or isotropic enamel using
the finite element method. A computed tomography was imported to an image
processing program to create the tooth model which was exported to a 3D modeling
program. The mechanical properties and loading conditions were prescribed in
Abaqus. In order to evaluate stresses, axial and oblique loads were applied
simulating realistic conditions. Compression stress was observed on the side of
load application, and tensile stress was observed on the opposite side. Tensile
stress was concentrated mainly in the cervical region and in the alveolar
insertion bone. Although stress concentration analyses of the isotropic 3D models
produced similar stress distribution results when compared to the anisotropic
models, tensile stress values shown by anisotropic models were smaller than the
isotropic models. Oblique loads resulted in higher values of tensile stresses,
which concentrate mainly in the cervical area of the tooth and in the alveolar
bone insertion. Anisotropic properties must be utilized in enamel stress
evaluation in non-carious cervical lesions.
PMID- 25850986
TI - beta-Octakis(methylthio)porphycenes: synthesis, characterisation and third order
nonlinear optical studies.
AB - A novel electron deficient beta-octakis(methylthio)porphycene, along with its
Zn(ii) and Ni(ii) derivatives, was synthesized for the first time. The
macrocyclic structure exhibits core ruffling with a largely red shifted
absorption band (~750 nm) and also a large enhancement in the third order
nonlinear optical response.
PMID- 25850985
TI - Performance investigation of SP3 and diffusion approximation for three
dimensional whole-body optical imaging of small animals.
AB - The third-order simplified harmonic spherical approximation (SP3) and diffusion
approximation (DA) equations have been widely used in the three-dimensional (3D)
whole-body optical imaging of small animals. With different types of tissues,
which were classified by the ratio of u s'/u alpha, the two equations have their
own application scopes. However, the classification criterion was blurring and
unreasonable, and the scope has not been systematically investigated until now.
In this study, a new criterion for classifying tissues was established based on
the absolute value of absorption and reduced scattering coefficients. Using the
newly defined classification criterion, the performance and applicability of the
SP3 and DA equations were evaluated with a series of investigation experiments.
Extensive investigation results showed that the SP3 equation exhibited a better
performance and wider applicability than the DA one in most of the observed
cases, especially in tissues of low-scattering-low-absorption and low-scattering
high-absorption range. For the case of tissues with the high-scattering-low
absorption properties, a similar performance was observed for both the SP3 and
the DA equations, in which case the DA was the preferred option for 3D whole-body
optical imaging. Results of this study would provide significant reference for
the study of hybrid light transport models.
PMID- 25850987
TI - Pharmacokinetics and pharmacodynamics of continuous infusion meropenem in
overweight, obese, and morbidly obese patients with stable and unstable kidney
function: a step toward dose optimization for the treatment of severe gram
negative bacterial infections.
AB - BACKGROUND: Meropenem is an anti-Gram-negative antimicrobial, the time-dependent
activity of which may be maximized through administration by continuous infusion.
OBJECTIVES: The objectives of this study were to characterize the
pharmacokinetics of continuous infusion meropenem in relation to body size and
Cockcroft-Gault estimated creatinine clearance (CLCR) in overweight and obese
patients with stable and unstable kidney function with the intent of creating a
nomogram for optimal dosing. PATIENTS AND METHODS: Patients from a single
institution with a body mass index >=25 kg/m(2) receiving meropenem by continuous
infusion with measurement of meropenem steady-state concentrations (C ss) were
identified. Individual Bayesian estimates of meropenem volume of distribution of
the central compartment (V c) and clearance (CL) were calculated and
relationships to body size descriptors and CLCR estimated using these body size
descriptors were defined by regression. Kidney function stability was defined
based on median absolute deviation, stratification by the ratio of maximum to
minimum serum creatinine (SCr) and individual patient-level regression of SCr
over time. The influence of kidney function stability on meropenem CL estimation
by CLCR was tested. RESULTS: A total of 375 patients (77.9 % male) with 846 C ss
values (62.4 % of patients with >=2 measurements) were identified. The median
daily dose of meropenem and frequency of infusion bag changes were 2000 mg/day
and four times per day, respectively. The meropenem C ss values were >=16, >=8,
>=4, and >=2 mg/L for 41.1, 76.1, 97.4, and 99.9 % of observations, respectively.
The median (range) age, weight, and BMI were 66 (24-90) years, 90 (70-250) kg,
and 30.8 (25.1-81.6) kg/m(2), respectively. The mean [standard deviation (SD)]
serum creatinine at baseline was 1.57 (1.37) mg/dL. The mean (SD) V c was 28.1
(1.36) L and not related to body size, while CL was 8.85 (6.40) L/h and best
related to CLCR estimated using adjusted body weight (ABW). The meropenem CL to
CLCR relationship was not significantly impacted by the presence or absence of
kidney function stability. The user-friendly dosing nomogram based on CLCR
estimated using ABW showed that optimal drug exposure [Css >= minimum inhibitory
concentration (MIC)] may be obtained even against multi-drug resistant (MDR)
pathogens when considering dosages up to 1250 mg every 6 h by continuous
infusion. CONCLUSIONS: Meropenem CL is best estimated using CLCR with ABW in
patients with a BMI >=25 kg/m(2) and this relationship is not altered by unstable
kidney function. Application of our dosing nomogram may improve the care of
overweight and obese patients with severe MDR Gram-negative infections treated
with meropenem by continuous infusion.
PMID- 25850988
TI - Immunoregulatory cytokine networks: 60 years of learning from murine
cytomegalovirus.
AB - Innate immunity defends against infection but also mediates immunoregulatory
effects shaping innate and adaptive responses. Studies of murine cytomegalovirus
(MCMV) infections have helped elucidate the mechanisms inducing, as well as the
elicited soluble and cellular networks contributing to, innate immunity.
Specialized receptors are engaged by infection-induced structures to stimulate
production of key innate cytokines. These then stimulate cytokine and cellular
responses such as activation of natural killer (NK) cells to mediate elevated
killing by type 1 interferon (IFN) and/or to produce the pro-inflammatory and
antiviral cytokine IFN-gamma by interleukin 12 (IL-12). An inter-systemic loop,
with IL-6 inducing glucocorticoid release, negatively regulates these early
cytokine responses. As infections advance into periods of overlapping innate and
adaptive responses, however, the cells are intrinsically conditioned to modify
the biological effects of exposure to individual cytokines. Some pathways are
turned off to inhibit an existing, whereas others are broadened for acquisition
of a new, response function. Remarkably, extended NK cell proliferation during
MCMV infection is associated with epigenetic modifications shifting the state of
the inhibitory cytokine IL-10 gene from closed to open and results in their
becoming equipped to produce this cytokine. When induced, NK cell IL-10
negatively regulates the magnitude of adaptive responses to protect against
immune pathology. Thus, innate immunoregulatory cytokine networks are integral to
pro-inflammatory and defense functions, but responding cells have the flexibility
to undergo cell intrinsic conditioning with changing network characteristics to
result in a new negative immunoregulatory function, and consequently, both
promote beneficial and limit detrimental immune responses.
PMID- 25850990
TI - Measuring coral size-frequency distribution using stereo video technology, a
comparison with in situ measurements.
AB - Coral colony size-frequency distribution data offer valuable information about
the ecological status of coral reefs. Such data are usually collected by divers
in situ, but stereo video is being increasingly used for monitoring benthic
marine communities and may be used to collect size information for coral
colonies. This study compared the size-frequency distributions of coral colonies
obtained by divers measuring colonies 'in situ' with digital video imagery
collected using stereo video and later processed using computer software. The
size-frequency distributions of the two methods were similar for corymbose
colonies, although distributions were different for massive, branching and all
colonies combined. The differences are mainly driven by greater abundance of
colonies >50 cm and fewer colonies <10 cm recorded when using the in situ method.
The stereo video method detected 93% of marked colonies >5 cm and was able to
record measurements on 87% of the colonies detected. However, stereo video only
detected 57% of marked colonies <5 cm, suggesting that this method may be
unsuitable for assessing abundance of coral recruits. Estimates of colony size
made with the stereo video were smaller than the in situ technique for all growth
forms, particularly for massive morphologies. Despite differences in size
distributions, community assessments, which incorporated genera, growth forms and
size, were similar between the two techniques. Stereo video is suitable for
monitoring coral community demographics and provided data similar to in situ
measure for corymbose corals, but the ability to accurately measure massive and
branching coral morphologies appeared to decline with increasing colony size.
PMID- 25850989
TI - An endocytic YXXPhi (YRRF) cargo sorting motif in the cytoplasmic tail of murine
cytomegalovirus AP2 'adapter adapter' protein m04/gp34 antagonizes virus evasion
of natural killer cells.
AB - Viruses have evolved proteins that bind immunologically relevant cargo molecules
at the cell surface for their downmodulation by internalization. Via a tyrosine
based sorting motif YXXPhi in their cytoplasmic tails, they link the bound cargo
to the cellular adapter protein-2 (AP2), thereby sorting it into clathrin
triskelion-coated pits for accelerated endocytosis. Downmodulation of CD4
molecules by lentiviral protein NEF represents the most prominent example. Based
on connecting cargo to cellular adapter molecules, such specialized viral
proteins have been referred to as 'connectors' or 'adapter adapters.' Murine
cytomegalovirus glycoprotein m04/gp34 binds stably to MHC class-I (MHC-I)
molecules and suspiciously carries a canonical YXXPhi endocytosis motif YRRF in
its cytoplasmic tail. Disconnection from AP2 by motif mutation ARRF should retain
m04-MHC-I complexes at the cell surface and result in an enhanced silencing of
natural killer (NK) cells, which recognize them via inhibitory receptors. We have
tested this prediction with a recombinant virus in which the AP2 motif is
selectively destroyed by point mutation Y248A, and compared this with the
deletion of the complete protein in a Deltam04 mutant. Phenotypes were
antithetical in that loss of AP2-binding enhanced NK cell silencing, whereas
absence of m04-MHC-I released them from silencing. We thus conclude that AP2
binding antagonizes NK cell silencing by enhancing endocytosis of the inhibitory
ligand m04-MHC-I. Based on a screen for tyrosine-based endocytic motifs in
cytoplasmic tail sequences, we propose here the new hypothesis that most proteins
of the m02-m16 gene family serve as 'adapter adapters,' each selecting its
specific cell surface cargo for clathrin-assisted internalization.
PMID- 25850991
TI - Mercury in the blue tilapia Oreochromis aureus from a dam located in a mining
region of NW Mexico: seasonal variation and percentage weekly intake (PWI).
AB - Uptake of mercury (Hg) through fish consumption is one of the key aspects of the
Hg cycle in the aquatic ecosystems. In tropical latitudes, biomonitoring of Hg in
freshwater reservoirs is scarce. The objectives of the study were to determine Hg
distribution in muscle, liver, and kidney of blue tilapia Oreochromis aureus from
a dam located in a mining region of northwest Mexico, to define temporal
variations of Hg concentrations in fish collected during the dry and rainy
seasons, and to estimate the percentage weekly intake (PWI) of Hg through fish
consumption considering the individual weekly intake of fish in Mexico and the
provisional tolerable weekly intake of Hg (5 MUg kg(-1) body weight). The
sequence of Hg concentrations was liver > kidney > muscle during the rainy season
and kidney > liver > muscle during the dry season. Levels of Hg were
significantly higher (p < 0.001) in muscle (0.36 MUg g(-1)) and kidney (0.65 MUg
g(-1)) of specimens collected during the dry season in comparison to individuals
collected during the rainy season; accordingly, average PWI in the dry season
(5.41) was higher than in the rainy season (1.80). Though collected fish were
adults, Hg levels in the edible portion are not harmful to consumers, even during
the dry season that Hg levels were higher.
PMID- 25850992
TI - Colonization of Legionella species in Turkish baths in hotels in Alanya, Turkey.
AB - This study evaluated the prevalence of Legionella species in water samples
collected from Turkish baths in hotels in Alanya, Turkey, from August 2003 to
September 2013. Water samples were collected in 100-mL sterile containers and
then concentrated by filtration. Heat treatment was used to eliminate other
microorganisms from the samples, which were then spread on Legionella-selective
buffered charcoal yeast extract alpha (BCYE-alpha) agar and on BCYE-alpha agar
supplemented with glycine, vancomycin, polymyxin, and cycloheximide. Cysteine
dependent colonies were identified by latex agglutination. In total, 135 samples
from 52 hotels with Turkish baths were evaluated. Legionella species were
identified in 11/52 (21.2%) hotels and 18/135 (13.3%) samples. The most
frequently isolated species was Legionella pneumophila, with most isolates
belonging to serogroups 6 (55.6%) and 1 (22.2%). The colony count was <100 colony
forming units (CFU) mL(-1) in nine samples, from 100 to 1000 CFU mL(-1) in six
samples, and >1000 CFU mL(-1) in three samples. These findings suggest that the
hot water systems of Turkish baths in hotels must be viewed as a possible source
of travel-associated Legionnaires' disease, and preventative measures should be
put in place.
PMID- 25850993
TI - Distribution and source apportionment of polycyclic aromatic hydrocarbons in the
surface soil of Baise, China.
AB - To estimate the distribution and sources of polycyclic aromatic hydrocarbons
(PAHs) in the soils of Baise, in southwest China, soil sampling sites were
selected from industry, traffic, rubbish, gas station, residential, and suburban
areas for analysis of PAHs. The average concentrations of ?16PAHs in the present
study varied significantly, depending on the sampling location, and ranged from
16.8 to 6,437.0 MUg/kg (dry weight basis), with a mean value of 565.8 MUg/kg. PAH
concentrations decreased significantly along the industry-traffic-rubbish-gas
station-residential-suburban transect. The PAH profiles in the surface soil of
the different areas imply that either source proximity to the sampling sites, or
transport and deposition effects influenced PAH distributions. Two diagnostic
ratios were selected and used to apportion PAH sources in the surface soil, and
bivariate plots show general trends of covariation. Principal component analysis
and multivariate linear regression were used to determine the primary sources and
their contributions of PAHs to the soils. The model showed that factors 1 (coal
and wood combustion) and 2 (petroleum combustion) contributed over 52.1 and 32.5%
of the total source of soil PAHs, respectively. The remaining 15.4% came from
evaporative and uncombusted petroleum.
PMID- 25850994
TI - What doesn't kill you makes you fat!
PMID- 25850995
TI - Conservative management of neurocysticercosis in a patient with hematopoietic
stem cell transplantation: a case report and review.
AB - Neurocysticercosis, an infection of the central nervous system with the larval
stage of the cestode Taenia solium, is common in developing countries but its
occurrence and management in allogeneic hematopoietic stem cell transplantation
(HSCT) has not been reported previously, to our knowledge. We report the case of
an immigrant female patient who underwent a matched-related allogeneic HSCT for
acute lymphoblastic leukemia and was incidentally found to have a solitary viable
neurocysticercosis lesion. However, despite severe immunosuppression, the size of
the cyst did not increase. More importantly, restoration of the immune system did
not induce significant inflammation or seizures. Subsequent follow-up
demonstrated complete resolution of the neurocysticercosis lesion. Thus, in the
setting of HSCT, an asymptomatic patient with a single neurocysticercosis lesion
was successfully managed without the use of anthelmintics, steroids, or anti
epileptics.
PMID- 25850997
TI - Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic
antiphospholipid syndrome.
AB - INTRODUCTION: Rivaroxaban can affect lupus anticoagulant (LA) testing and
antiphospholipid antibodies (aPL) may interfere with the anticoagulant action of
rivaroxaban. AIMS: To establish the influence of rivaroxaban on LA detection and
of aPL on the anticoagulant action of rivaroxaban. METHODS: Rivaroxaban and 52
IgG preparations (20 LA+ve, 12 LA-ve thrombotic antiphospholipid syndrome [APS]
patients, and 20 normal controls [NC]) were spiked into pooled normal plasma
(PNP) for relevant studies. LA detection was also studied in APS patients
receiving rivaroxaban 20 mg once daily. RESULTS: In vitro spiking of samples with
rivaroxaban showed no false positive LA with Textarin time, Taipan venom
time/Ecarin clotting time (TVT/ECT), dilute prothrombin time (dPT) and in-house
dilute Russell's viper venom time (DRVVT), but false positives in the majority of
NC and LA negative IgG with two commercial DRVVT reagents at 250 ng/mL but not 50
ng/mL rivaroxaban. Ex vivo studies: six LA+ve patients on rivaroxaban remained LA
positive with TVT/ECT and DRVVT at peak (162-278 ng/mL) and trough (30-85 ng/mL)
rivaroxaban levels. Six LA-ve patients became (apparently) LA+ve with two DRVVT
reagents (test/confirm ratio median [confidence interval], 1.6 [1.3-1.8], 1.6
[1.4-1.9]) but not with TVT/ECT at peak rivaroxaban levels, and remained LA-ve
with both DRVVT reagents and TVT/ECT at trough levels. aPL positive IgG spiking
of PNP had no effect on rivaroxaban's anticoagulant action on thrombin generation
or rivaroxaban anti-Xa levels. CONCLUSIONS: The TVT/ECT ratio and Textarin time
were not affected even at peak rivaroxaban levels, enabling detection of LA ex
vivo. aPL had no effects on rivaroxaban's anticoagulant action in vitro.
PMID- 25850996
TI - Whole exome sequencing identifies driver mutations in asymptomatic computed
tomography-detected lung cancers with normal karyotype.
AB - The efficacy of curative surgery for lung cancer could be largely improved by non
invasive screening programs, which can detect the disease at early stages. We
previously showed that 18% of screening-identified lung cancers demonstrate a
normal karyotype and, following high-density genome scanning, can be subdivided
into samples with 1) numerous; 2) none; and 3) few copy number alterations. Whole
exome sequencing was applied to the two normal karyotype, screening-detected lung
cancers, constituting group 2, as well as normal controls. We identified
mutations in both tumors, including KEAP1 (commonly mutated in lung cancers) in
one, and TP53, PMS1, and MSH3 (well-characterized DNA-repair genes) in the other.
The two normal karyotype screening-detected lung tumors displayed a typical lung
cancer mutational profile that only next generation sequencing could reveal,
which offered an additional contribution to the over-diagnosis bias concept
hypothesized within lung cancer screening programs.
PMID- 25850998
TI - Is cystic echinoccocosis re-emerging in western Spain?
AB - Cystic echinococcosis (CE) remains an important health problem in many areas of
the world, including the Mediterranean region. We performed a retrospective study
of cases reported from 1998 to 2012 in order to review and update the
epidemiology of this disease in a highly endemic area situated in western Spain.
A total of 471 patients were diagnosed with hydatid disease. Of these cases,
55.8% were male, with an average age of 62.3 +/- 19.5 years. More importantly,
1.5% of patients were children, and 20.5% were aged <45 years. An active
therapeutic approach was implemented for 92.6% of the CE patients with primary
diagnoses; however, a 'watch and wait' strategy was used in 59.3% of all
secondary CE diagnoses. The incidence rate of hydatid disease was significantly
higher compared to the incidence described in the Notifiable Disease System in
this area. Furthermore, a significant decrease in hydatid incidence during the
years included in the study was observed (beta = -0.4357, P < 0.001). CE
incidence has diminished in recent years, although active transmission remains in
paediatric cases. Additionally, CE incidence remains high in our region despite
public health plans for its control. The documented incidence of CE disease
clearly underestimates the real numbers.
PMID- 25851000
TI - Genome-wide DArT and SNP scan for QTL associated with resistance to stripe rust
(Puccinia striiformis f. sp. tritici) in elite ICARDA wheat (Triticum aestivum
L.) germplasm.
AB - KEY MESSAGE: Identified DArT and SNP markers including a first reported QTL on
3AS, validated large effect APR on 3BS. The different genes can be used to
incorporate stripe resistance in cultivated varieties. Stripe rust [yellow rust,
caused by Puccinia striiformis f. sp. tritici (Pst)] is a serious disease in
wheat (Triticum aestivum). This study employed genome-wide association mapping
(GWAM) to identify markers linked to stripe rust resistance genes using Diversity
Arrays Technology (DArT((r))) and single-nucleotide polymorphism (SNP) Infinium
9K assays in 200 ICARDA wheat genotypes, phenotyped for seedling and adult plant
resistance in two sites over two growing seasons in Syria. Only 25.8 % of the
genotypes showed resistance at seedling stage while about 33 and 44 % showed
moderate resistance and resistance response, respectively. Mixed-linear model
adjusted for false discovery rate at p < 0.05 identified 12 DArT and 29 SNP
markers on chromosome arms 3AS, 3AL, 1AL, 2AL, 2BS, 2BL, 3BS, 3BL, 5BL, 6AL, and
7DS significantly linked to Pst resistance genes. Of these, the locus on 3AS has
not been previously reported to confer resistance to stripe rust in wheat. The
QTL on 3AS, 3AL, 1AL, 2AL, and 2BS were effective at seedling and adult plant
growth stages while those on 3BS, 3BL, 5BL, 6AL and 7DS were effective at adult
plant stage. The 3BS QTL was validated in Cham-6 * Cham-8 recombinant inbred line
population; composite interval analysis identified a stripe resistance QTL
flanked by the DArT marker, wPt-798970, contributed by Cham-6 parent which
accounted for 31.2 % of the phenotypic variation. The DArT marker "wPt-798970"
lies 1.6 cM away from the 3BS QTL detected within GWAM. Epistatic interactions
were also investigated; only the QTL on 1AL, 3AS and 6AL exhibited interactions
with other loci. These results suggest that GWAM can be an effective approach for
identifying and improving resistance to stripe rust in wheat.
PMID- 25851001
TI - Physical mapping of chromosome 4J of Thinopyrum bessarabicum using gamma
radiation-induced aberrations.
AB - KEY MESSAGE: Gamma radiation induced a series of structural aberrations involving
Thinopyrum bessarabicum chromosome 4J. The aberrations allowed for deletion
mapping of 101 4J-specific markers and fine mapping of blue-grained gene BaThb.
Irradiation can induce translocations and deletions to assist physically locating
genes and markers on chromosomes. In this study, a 12-Gy dosage of (60)Co-gamma
was applied to pollen and eggs of a wheat (Triticum aestivum) landrace Chinese
Spring (CS)-Thinopyrum bessarabicum chromosome 4J disomic addition line (DA4J),
and the gametes from irradiated plants were fertilized with normal CS eggs or
pollen to produce M1 seeds. Based on genomic in situ hybridization analysis of
261 M1 plants, we identified 74 lines carrying structural aberrations involving
chromosome 4J with the higher aberration rate in treated pollen (31.2 %) than in
the treated eggs (21.3 %). We further identified 43 (53.8 %) lines with
structural aberrations on chromosome 4J by analyzing another 80 M1 plants with 74
4J-specific markers, indicating that combining molecular and cytological methods
was more efficient for detecting chromosome aberrations. Marker analysis thus was
performed prior to cytogenetic identification on M2-M4 seeds to detect chromosome
structural aberrations. Sixty-eight M3 lines with structural aberrations on
chromosome 4J and six previously obtained chromosome 4J alien lines were then
analyzed using 101 chromosome 4J-specific markers. After combining marker results
with chromosome aberrations in each line, chromosome 4J was physically divided
into 24 segmental blocks with 7 in the short arm and 17 in the long arm. The blue
grained gene BaThb was further mapped into the region corresponding to block 4JL
11. The chromosome aberrations and the physical map developed in this research
provide useful stocks and tools for introgression of genes on chromosome 4J into
wheat.
PMID- 25850999
TI - Genetics in child and adolescent psychiatry: methodological advances and
conceptual issues.
AB - Discovering the genetic basis of early-onset psychiatric disorders has been the
aim of intensive research during the last decade. We will first selectively
summarize results of genetic research in child and adolescent psychiatry by using
examples from different disorders and discuss methodological issues, emerging
questions and future directions. In the second part of this review, we will focus
on how to link genetic causes of disorders with physiological pathways, discuss
the impact of genetic findings on diagnostic systems, prevention and therapeutic
interventions. Finally we will highlight some ethical aspects connected to
genetic research in child and adolescent psychiatry. Advances in molecular
genetic methods have led to insights into the genetic architecture of psychiatric
disorders, but not yet provided definite pathways to pathophysiology. If
replicated, promising findings from genetic studies might in some cases lead to
personalized treatments. On the one hand, knowledge of the genetic basis of
disorders may influence diagnostic categories. On the other hand, models also
suggest studying the genetic architecture of psychiatric disorders across
diagnoses and clinical groups.
PMID- 25851002
TI - Genotyping-by-sequencing (GBS) identified SNP tightly linked to QTL for pre
harvest sprouting resistance.
AB - KEY MESSAGE: Using a GBS-SNP map, a QTL for pre-harvest sprouting resistance on
4AL of Totoumai A was delimited to 2.9-cM interval, and SNP closely linked to
several other QTL were identified. Pre-harvest sprouting (PHS) of wheat is a
major constraint to wheat production in many wheat-growing areas worldwide,
because it reduces both wheat grain yield and the end-use quality. To identify
markers tightly linked to the quantitative trait loci (QTL) for PHS resistance
and seed dormancy (SD), we evaluated 155 recombinant inbred lines (RIL) derived
from a cross between a PHS-resistant parent 'Tutoumai A' and a PHS-susceptible
parent 'Siyang 936' for single-nucleotide polymorphisms (SNP) using genotyping-by
sequencing (GBS), and for PHS resistance and SD using both field and greenhouse
grown plants. Two SNP, GBS109947 and GBS212432, were mapped to a major QTL region
for PHS resistance and SD on chromosome 4AL, and delimited the QTL to a 2.9-cM
interval. Two and nine additional SNP were mapped to minor QTL regions for SD on
chromosome 5B and 5A, respectively. Critical SNP in these QTL regions were
converted into KBioscience Competitive Allele-Specific PCR (KASP) assays that can
be easily used for marker-assisted selection to improve PHS resistance.
PMID- 25851003
TI - Commissural region dehiscence from the stent post of Carpentier-Edwards
bioprosthetic cardiac valves.
AB - Structural deterioration is the major reason for reoperation in patients with
valvular bioprostheses. We present findings on a mode of structural
deterioration, the pathology of which has not yet been well characterized.
Between January 1990 and December 1992, 39 Carpentier-Edwards standard valves
(CESTD) and 50 Carpentier-Edwards supra-annular valves (CESAV) were operatively
removed at St. Paul's Hospital. Of these, 14 bioprostheses (6 CESTD [15%] and 8
CESAV [16%]) showed dehiscence of a single commissural region from its stent
post. Age at initial implantation was not significantly different between
patients with CESAV (52.1 +/- 5.4 years) and CESTD (45.5 +/- 5.1 years, p = ns),
but time from implantation to reoperation was shorter for CESAV as compared with
CESTD (7.9 +/- 0.5 vs. 13.3 +/- 0.7 years, respectively, p < 0.01). The vast
majority (12 14 ) of dehiscences were in mitral bioprostheses, and all patients
presented with valvular regurgitation. Accompanying structural changes
(calcification and cuspal tears/perforations), graded semiquantitatively (absent
= 0, mild = 1, moderate = 2, and severe = 3), ranged from absent to severe in
individual valves. Radiographically detected calcification was greater in CESTD
compared with CESAV (CESTD 1.3 +/- 0.3 vs. CESAV 0.5 +/- 0.3, p < 0.05).
Differences in severity of cuspal tears or perforations were not present. Thus,
commissural region dehiscence from the stent post of Carpentier-Edwards porcine
bioprosthetic valves in the mitral position is a relatively common form of
structural deterioration associated with valvular incompetence. It may occur more
readily in Carpentier-Edwards supra-annular valves.
PMID- 25851004
TI - The encapsulation of polyurethane-insulated transvenous cardiac pacemaker leads.
AB - When cardiac pacemakers are implanted, the tranvenous route is typically
preferred. For dual chamber pacemakers, an atrial and a ventricular lead are
required. Based on postmortem examination of 101 canines with polyurethane
insulated leads implanted from 10 days through 13 years, encapsulation of these
leads is initiated by thrombus secondary to endothelial damage and/or blood flow
perturbations. Organization of thrombus results in a vascularized collagenous
capsule. With continued blood flow perturbation, more thrombi can form and
reorganize to cause the collagenous capsules to grow with implant time. Under
certain conditions, the encapsulating sheath can differentiate into cartilage,
mineralized tissue, and even bone. The least commonly encapsulated area is in or
just superior to the annulus of the valve. The most common locations for capsule
formation are within the upper right atrium (where two leads are often bound
together by the tissue) and the right ventricle. The ventricular sheaths are
often adhered firmly to tricuspid valve structures. The presence of relatively
large, friable, partially organized thrombi on chronic leads is not unusual, even
after more than 10 years' implantation. It is recommended that chronic leads be
imaged prior to attempts to remove them to detect the presence and location of
embolizable structures.
PMID- 25851005
TI - AIDS and the heart: Clinicopathologic assessment.
AB - Acquired immune deficiency syndrome (AIDS) is responsible for significant
morbidity and mortality in the United States and other countries. Cardiac
involvement in AIDS, which was previously felt to be an unusual manifestation of
the disease, is now being described with increasing frequency. Clinical and
necropsy studies have demonstrated myocarditis, myocardial necrosis,
cardiomyopathy, pericardial disease, endocarditis, pulmonary hypertension, and
tumor infiltration in patients dying with AIDS. A direct role for human
immunodeficiency virus (HIV-1) in the development of myocarditis, myocardopathy,
and pericardial disease has not yet been elucidated. Recent immunopathological
evidence suggests a possible role for immune-mediated myocardial inflammatory
changes. The drugs used to treat HIV-1 have not been shown to be cardiotoxic;
however, there are suggestions that azidothymidine (AZT) can cause mitochondrial
changes in myocardial muscle. There are also suggestions that the cardiac
complications of AIDS are different in patients whose risk factor for HIV
infection is homosexual practice compared with patients having intravenous drug
addiction as their major risk factor for HIV disease. Risk factors for myocardial
disease, other than HIV, may also be contributors to cardiac complications in
patients with AIDS who are intravenous drug abusers.
PMID- 25851006
TI - Myocyte nuclear area as a measure of left ventricular hypertrophy in transplant
patients.
AB - Transplanted hearts have been reported to increase in size/weight in the first
few months after transplant and to remain stable thereafter. An indirect way of
assessing the changes in heart weight is through the changes in the area of the
myocyte nucleus (MNA). We studied 20 patients who had undergone orthotopic heart
transplantation more than 12 months previously; 10 had become hypertensive, and
the remaining 10 were normotensive. Myocardial biopsies taken the first week
after transplant and 6, 12, 24, and 52 weeks after transplant were assessed.
Myocyte nuclear area was measured in 200 myocytes/biopsy with an image analyzer.
Individual measurements showed a wide variation in MNA, with significant overlaps
among the different biopsies. Assessment of MNA at one year showed increased MNA
in 4 10 patients in the hypertensive group and 5 10 in the normotensive group.
The remaining patients showed either no statistically significant changes in MNA
or a significant (p < 0.0001) decrease in MNA. The presence of systemic
hypertension was not a predictive factor for significant hypertrophy and, in some
cases, not even for hypertrophy itself. We conclude that although there is often
an increase in MNA of the transplanted heart at one year posttransplant, this
increase is not systematic, and isolated morphometric results should be viewed
cautiously.
PMID- 25851007
TI - Characteristics of a model of myocardial infarction produced by coronary artery
ligation in the rat.
AB - The rat model of coronary artery ligation is widely used to study myocardial
infarction, ventricular remodeling, and congestive heart failure. Total infarct
size and the relationship between endocardial and epicardial infarction were
characterized in 691 animals that survived permanent ligation of the left
coronary artery. Infarct size was determined from serial histologic sections of
the left ventricle (LV), followed by planimetry of muscle and scar
circumferences. Mean infarct size was 34.5% +/- 13.3% of total left ventricular
circumference. Rats surviving longer durations to terminal study had a smaller
mean infarct size. Infarct transmurality, as described by the ratio of epicardial
to-endocardial infarct sizes, was 0.78 +/- 0.01. The transmurality ratio
increased and its variability decreased as infarct size increased. Subendocardial
infarcts were more frequent among small infarcts and had smaller areas of
endocardial infarction. Although infarct size was highly variable, infarct size
indexed to endocardial infarct size was less variable. Infarct size indexed to
endocardial infarct size may therefore represent a significantly more powerful
method for assessing the effects of treatments to reduce infarct size.
PMID- 25851008
TI - Contact sites between the inner and outer mitochondrial membranes in stunned
versus hibernating myocardium.
AB - This study characterizes the energy state and the influence of calcium on
myocardial stunning and chronic hibernation via the quantification of a calcium
sensitive phenomenon known as mitochondrial contact sites. For stunning, the left
anterior descending artery of mongrel dogs was occluded for 15 minutes, followed
by a 150-minute reperfusion; for chronic hibernation, we used human biopsies
obtained during coronary artery bypass graft (CABG) from viable (positron
emission tomography-controlled) asynergic areas. Both sample groups were
processed for electron microscopy, and the ratio of surface densities of contact
sites to mitochondrial membranes was quantified with morphometry. Therefore a
cycloidal pattern was superimposed on the electron micrographs, and the ratio
between the total number of intersections between cycloids and contact sites and
the total number of intersections between cycloids and mitochondrial membranes is
the ratio of surface densities (Ss). In stunned cells, Ss = 0.46 +/- 0.06, which
is significantly higher than the ratio in the normokinetic cells, Ss = 0.355 +/-
0.003, although the general ultrastructure of the subcellular compartments is
practically identical to those in the normoxic area. The distinction between
cells affected by chronic hibernation and normal cells was based on structural
criteria. The ratio of surface densities, expressed Ss = 0.27 +/- 0.05, was
significantly lower than the ratio in the normoxic area (Ss = 0.356 +/- 0.005).
The high ratio of surface densities in the stunned cells lends credibility to the
notion that stunning implies an increased intracellular calcium content and
energy demand, whereas hibernation might be a kind of low demand-low supply
situation with a low intracellular calcium level.
PMID- 25851009
TI - Beneficial effects of gangliosides on the natural history of acute chagasic
myocarditis in rats.
AB - This study was designed to investigate the effects of ganglioside treatment on
acutely Trypanosoma cruzi-infected rats with emphasis on the heart. Newly weaned
Wistar rats were infected with T. cruzi (Colombian strain, 50,000 parasites/kg
body weight injected intraperitoneally). Two groups of 25 infected rats received
daily injections of saline or ganglioside (10 mg/kg body weight)
intraperitoneally between the 14th and 30th days after infection. Two groups of
10 noninfected rats were similarly treated. On day 31, all surviving rats were
killed. Hearts were collected for histopathology and norepinephrine assay. An
arbitrary score for myocardial microscopic lesions was used to characterize each
heart wall. Mortality was recorded throughout the experimental period. Seven of
25 (28%) ganglioside-treated and 14 of 25 (56%) saline-treated rats died
spontaneously (p = 0.02). The histological score was 5.4 +/- 3.2 for ganglioside
treated and 7.9 +/- 3.0 for saline-treated rats (p < 0.05). No difference was
detected in myocardial norepinephrine content. Thus, ganglioside treatment
decreases mortality and myocardial inflammation in acute chagasic myocarditis in
rats.
PMID- 25851010
TI - Nonbacterial thrombotic versus infective endocarditis: A necropsy study of 320
cases.
AB - The precise relationship between nonbacterial thrombotic endocarditis (NBTE) and
infective endocarditis (IE) remains to be clearly established, some believing
that IE might develop from NBTE once the latter becomes secondarily infected
during bacteremia. To compare the features of the two lesions, 175 cases of NBTE
and 145 cases of IE encountered in more than 25,000 autopsies performed over a
period of 24 years (1970-1993) were reviewed, and the relevant clinical,
pathological, and bacteriological findings assessed. The results show that IE is
a genuine suppurative infection of cardiac valves ab initio, whereas, in NBTE,
inflammation is lacking and the lesion is a result of a usually paraneoplastic
disturbance of thrombosis/thrombolysis.
PMID- 25851011
TI - Cholesterol embolization to the coronary arteries resulting in acute myocardial
infarction: A complication of coronary artery bypass grafting surgery.
AB - Cholesterol emboli dislodged during coronary artery bypass surgery may be
released downstream into the native coronary arteries and lead to the development
of acute myocardial infarction. An autopsy-proven case of such an event occurring
in a 79-year-old woman illustrates this complication of coronary artery bypass
surgery. Awareness of this complication by pathologists may facilitate its
recognition. Awareness by surgeons, on the other hand, may help to prevent it
through decreased intraoperative manipulation of the involved vessels.
PMID- 25851012
TI - Coronary artery intimal hyperplasia, occlusive platelet thrombus, and fatal
myocardial infarction in an intravenous cocaine user.
AB - A 38-year-old man died of an acute inferoposterior myocardial infarction, shortly
after intravenous injection of cocaine. At necropsy, diffuse intimal hyperplasia
and an occlusive platelet thrombus involved the left main, left anterior
descending, and the left circumflex coronary arteries. The possible relation of
these morphologic findings to the effects of cocaine on platelet and coronary
vascular function are discussed and the relevant literature is reviewed.
PMID- 25851013
TI - Cardiac allograft pathology: A comment on the problem of chronic rejection.
PMID- 25851014
TI - Cardiac allograft pathology-A comment on the problem of chronic rejection.
PMID- 25851015
TI - Ebstein's malformation.
PMID- 25851016
TI - Acute humoral rejection.
PMID- 25851017
TI - Work-related psychosocial risk factors and mental health problems amongst nurses
at a university hospital in Estonia: a cross-sectional study.
AB - AIM: Rapid changes in the Estonian health care system have placed extra pressure
on the nursing profession, but the potential impacts of psychosocial changes have
not been investigated. We aimed to explore the work-related psychosocial risk
factors and their relationships with mental health problems (MHPs) amongst nurses
at the university hospital in Estonia. METHODS: A cross-sectional survey was
undertaken amongst registered nurses at Tartu University Hospital (TUH).
Psychosocial work factors and MHPs (stress, somatic symptoms, depressive symptoms
and burnout) were measured using version two of the Copenhagen Psychosocial
Questionnaire (COPSOQ II). Descriptive statistics and Pearson's r correlation
with sequential Bonferroni correction were used to analyse the data. RESULTS: The
analysis was based on 404 nurses (45% of the full-time working population of
nurses). The highest mean scores recorded for the positive work-related
psychosocial factors studied were meaning of work, role clarity, social
relationships and mutual trust between employees. The highest scores for the
negative factors studied were the demands for hiding emotions, work pace,
cognitive and emotional demands. Stress and burnout showed the highest mean
scores amongst the MHPs. Quantitative and emotional demands were positively
related to all of the studied MHPs, while work pace and role conflicts had a
positive correlation with stress and burnout. All of the studied negative
psychosocial factors were significantly correlated with burnout. CONCLUSIONS:
work-related psychosocial risk factors such as quantitative demands work load,
emotional demands, work pace and role conflicts, had significant positive
relationships with MHPS in nurses in Estonia, and may contribute to high levels
of stress as well as burnout amongst nurses: .
PMID- 25851018
TI - Efficacy of dexmedetomidine on postoperative shivering: a meta-analysis of
clinical trials.
AB - PURPOSE: Shivering is a frequent complication in the postoperative period. The
aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on
postoperative shivering. METHODS: Two researchers independently searched PubMed,
EMBASE and the Cochrane Central Register of Controlled Trials for controlled
clinical trials. The meta-analysis was performed by Review Manager. RESULTS:
Thirty-nine trials with 2,478 patients were included in this meta-analysis.
Dexmedetomidine reduced postoperative shivering compared with placebo (risk ratio
[RR] = 0.26; 95% confidence interval [CI]: 0.20 to 0.34), with a minimum
effective dose of 0.5 ug.kg(-1) (RR = 0.36; 95% CI: 0.21 to 0.60). The anti
shivering effect can be achieved both intravenously and epidurally when
administered within two hours prior to the end of surgery. The efficacy of
dexmedetomidine was similar to widely used anti-shivering agents, such as
fentanyl, meperidine, tramadol, clonidine and so on; however, dexmedetomidine may
increase the incidence of sedation, hypotension, bradycardia and dry mouth.
CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows
superiority over placebo, but not over other anti-shivering agents. Therefore,
considering its high price and potential adverse events, dexmedetomidine may not
be appropriate solely for the purpose of the prevention of postoperative
shivering.
PMID- 25851019
TI - Extracorporeal membrane oxygenation for blastomycosis-related acute respiratory
distress syndrome: a case series.
AB - PURPOSE: Blastomyces dermatitidis is a dimorphic fungus endemic to North America
capable of causing fatal respiratory failure. Acute respiratory distress syndrome
(ARDS) complicates up to 10% of pulmonary blastomycosis in hospitalized patients
and carries a mortality of 50-90%. This report describes the clinical course of
four consecutive patients with blastomycosis-related ARDS treated with venovenous
extracorporeal membrane oxygenation (ECMO) during 2009-2014. CLINICAL FEATURES:
Four adults were referred from northwestern Ontario, Canada with progressive
respiratory illnesses. All patients developed diffuse bilateral opacities on
chest radiography and required mechanical ventilation within 6-72 hr. Patients
satisfied Berlin criteria for severe ARDS with trough PaO2/F i O2 ratios of 44-61
on positive end-expiratory pressure of 12-24 cm H2O. Wet mount microscopy from
respiratory samples showed broad-based yeast consistent with B.dermatitidis.
Despite lung protective ventilation strategies with maximal F i O2 (patients A
D), neuromuscular blockade (patients A-D), inhaled nitric oxide (patients A and
D), and prone positioning (patient D), progressive hypoxemia resulted in
initiation of venovenous ECMO by hours 24-90 of mechanical ventilation with
subsequent de-escalation of ventilatory support. In all four cases, ECMO
decannulation was performed (7-23 days), mechanical ventilation was withdrawn (18
52 days), and the patients survived to hospital discharge (31-87 days).
CONCLUSION: This report describes the successful application of ECMO as rescue
therapy in aid of four patients with refractory blastomycosis-associated ARDS. In
addition to early appropriate antimicrobial therapy, transfer to an institution
experienced with ECMO should be considered when caring for patients from endemic
areas with rapidly progressive respiratory failure.
PMID- 25851020
TI - Combined saphenous and sciatic catheters for analgesia after major ankle surgery:
a double-blinded randomized controlled trial.
AB - PURPOSE: Continuous sciatic nerve block is used for pain management following
major ankle surgery. Pain from the saphenous nerve territory often persists. We
conducted a double-blinded randomized placebo-controlled trial to evaluate the
effect of a supplementary saphenous catheter in the proximal thigh combined with
a popliteal sciatic catheter and single-shot saphenous nerve block after major
ankle surgery. METHODS: Fifty patients received both sciatic and saphenous
continuous catheters inserted along the short axis of the nerves with ultrasound
guidance. All patients had an initial sciatic nerve block followed by a
continuous sciatic catheter infusion and an initial saphenous nerve block with
ropivacaine. Participants were then randomized to infusion of either ropivacaine
or isotonic saline in the saphenous catheter for 48 hr postoperatively. The
primary outcome was total intravenous morphine consumption during the first 48 hr
postoperatively. Secondary outcomes were clinical analgesia, saphenous analgesia,
territory of worst pain, and patient satisfaction. RESULTS: Forty-four patients
were included in the analysis. The mean (SD) 48-hr morphine consumption was 24.7
(21.6) mg in the intervention group and 27.8 (20.1) mg in the placebo group (P =
0.63). The mean difference in 48-hr morphine consumption was 3.0 mg (95%
confidence interval, -9.7 to 15.7). There were no differences regarding the
secondary outcomes. CONCLUSION: A saphenous catheter with a low-dose continuous
infusion of ropivacaine, as an adjunct to a sciatic catheter, had no effect on
the postoperative analgesia after major ankle surgery when both catheters were
inserted along the short axis of the nerves. This trial was registered at
ClinicalTrials.gov (NCT01445210).
PMID- 25851024
TI - Bony nasolacrimal duct dehiscence in functional endoscopic sinus surgery:
radiological study and discussion of surgical implications.
AB - OBJECTIVES: To analyse the radiological features of the bony nasolacrimal duct
before and after functional endoscopic sinus surgery, and document the incidence
of surgically induced dehiscence. METHODS: A retrospective case series analysis
was conducted of 63 consecutive patients who underwent uncinectomy as a part of
118 functional endoscopic sinus surgical procedures. All patients underwent pre-
and post-operative computed tomography scans. Axial computed tomography images at
the level of maxillary sinus were evaluated for the presence of bony nasolacrimal
duct dehiscence, osteitis and completeness of uncinectomy. RESULTS: The rate of
nasolacrimal duct dehiscence prior to surgery was 6.8 per cent (8 out of 118
cases). Nasolacrimal duct dehiscence as a consequence of surgery was observed in
3.3 per cent of cases (4 out of 118), with a further 4.2 per cent (5 out of 118)
showing post-operative reactive bony change of the nasolacrimal duct in the
absence of dehiscence. CONCLUSION: The incidence of nasolacrimal duct injury
observed was much lower than that previously reported in the literature.
PMID- 25851023
TI - Interplay between chemotaxis and contact inhibition of locomotion determines
exploratory cell migration.
AB - Directed cell migration in native environments is influenced by multiple
migratory cues. These cues may include simultaneously occurring attractive
soluble growth factor gradients and repulsive effects arising from cell-cell
contact, termed contact inhibition of locomotion (CIL). How single cells
reconcile potentially conflicting cues remains poorly understood. Here we show
that a dynamic crosstalk between epidermal growth factor (EGF)-mediated
chemotaxis and CIL guides metastatic breast cancer cell motility, whereby cells
become progressively insensitive to CIL in a chemotactic input-dependent manner.
This balance is determined via integration of protrusion-enhancing signalling
from EGF gradients and protrusion-suppressing signalling induced by CIL, mediated
in part through EphB. Our results further suggest that EphB and EGF signalling
inputs control protrusion formation by converging onto regulation of
phosphatidylinositol 3-kinase (PI3K). We propose that this intricate interplay
may enhance the spread of loose cell ensembles in pathophysiological conditions
such as cancer, and possibly other physiological settings.
PMID- 25851025
TI - A Randomized Double Blind Clinical Trial on a Sabgh Formulation for Patients With
Vitiligo.
AB - BACKGROUND: The cosmetic problem that vitiligo produces affects patients
psychologically. Many patients with vitiligo are suggested to cover their white
skin patches with cosmetic products. There are formulations in traditional
Iranian pharmacy to color these white skin patches. In this study, one of these
formulations was compared with a cosmetic formulation. METHODS: Two groups of
patients were selected. One group used a marketed formulation and other group
used a traditional Iranian Pharmacy formulation. The quality of life of the
patients was compared based on the Dermatology Life Quality Index Questionnaire.
RESULTS: Both interventions were associated with statistically improved
Dermatology Life Quality Index scores over the 8-week intervention (P < .05),
although the difference between the 2 was not statistically significant (P =
.436). CONCLUSION: Traditional Iranian Pharmacy formulation is effective in
increasing the quality of life in vitiligo patients.
PMID- 25851026
TI - Combined hydrophobicity and mechanical durability through surface
nanoengineering.
AB - This paper reports combined hydrophobicity and mechanical durability through the
nanoscale engineering of surfaces in the form of nanorod-polymer composites.
Specifically, the hydrophobicity derives from nanoscale features of mechanically
hard ZnO nanorods and the mechanical durability derives from the composite
structure of a hard ZnO nanorod core and soft polymer shell. Experimental
characterization correlates the morphology of the nanoengineered surfaces with
the combined hydrophobicity and mechanical durability, and reveals the
responsible mechanisms. Such surfaces may find use in applications, such as boat
hulls, that benefit from hydrophobicity and require mechanical durability.
PMID- 25851027
TI - Candidemia Diagnosed from Peripheral Blood Smear: Case Report and Review of
Literature 1954-2013.
AB - BACKGROUND: Yeast with pseudohyphae or those that have been phagocytized by white
blood cells are coincidentally found in peripheral blood smears. The clinical
diagnostic value and outcome of candidaemia diagnosed from peripheral blood
smears (CPBSs) are unclear. CASE PRESENTATION: A 45-year-old man with diabetes
and panhypopituitarism for 20 years received 10 mg of hydrocortisone and 100 MUg
of levothyroxine sodium hydrate daily. He has been admitted seven times because
of adrenal failure triggered by infections and was admitted for pneumonia. On day
56, some budding yeast was found microscopically in a peripheral blood smear with
May-Giemsa staining. Some of them were phagocytized by white blood cells. The two
blood cultures yielded Candida parapsilosis. Despite antifungal treatment and
removal of an intravenous catheter, on day 98 (42 days after the candidaemia
diagnosis), the patient died. CONCLUSION: We analysed 36 cases including the
present case. Almost all CPBS patients (96.5 %, n = 29) were using an intravenous
catheter. The most frequently isolated species was C. parapsilosis (35.1 %),
followed by C. albicans (29.7 %). The overall mortality rate was 53.6 % (n = 28).
The time from the discovery of yeast-like pathogens using peripheral blood smears
to death ranged from a few hours to 93 days (median 19 days). The present results
suggest that intravenous catheter use and the underlying conditions of patients
are responsible for CPBSs. The detection of yeast in peripheral blood smears
suggests advanced infections with uncontrollable complications, which means a
poor prognosis. Rapid detection methods besides blood culture are needed.
PMID- 25851029
TI - Arm Orthosis/Prosthesis Movement Control Based on Surface EMG Signal Extraction.
AB - This paper shows experimental results on electromyography (EMG)-based system
control applied to motorized orthoses. Biceps and triceps EMG signals are
captured through two biometrical sensors, which are then filtered and processed
by an acquisition system. Finally an output/control signal is produced and sent
to the actuators, which will then perform the actual movement, using algorithms
based on autoregressive (AR) models and neural networks, among others. The
research goal is to predict the desired movement of the lower arm through the
analysis of EMG signals, so that the movement can be reproduced by an arm
orthosis, powered by two linear actuators. In this experiment, best accuracy has
achieved values up to 91%, using a fourth-order AR-model and 100ms block length.
PMID- 25851028
TI - Differentiation of focal nodular hyperplasia from hepatocellular adenoma: Role of
the quantitative analysis of gadobenate dimeglumine-enhanced hepatobiliary phase
MRI.
AB - PURPOSE: To determine the value of quantitative analysis of the hepatobiliary
phase (HBP) in gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance
imaging (MRI) to differentiate focal nodular hyperplasia (FNH) from
hepatocellular adenoma (HCA). MATERIALS AND METHODS: Thirty-eight patients
bearing 67 lesions (40 FNH; 27 HCA) were retrospectively included in this
Institutional Review Board-approved study. The same volumetric interpolated
breath-hold examination (VIBE) T1 -weighted sequences were performed before and
after contrast injection on a 1.5T MRI, with HBP images acquired with a mean
delay of 80 minutes (range 60-120 min). After a visual assessment of lesions
enhancement (qualitative HBP analysis), the HBP signal intensity ratio (SIR) and
the lesion-to-liver contrast enhancement ratio (LLCER) were calculated for each
lesion by two observers (Mann-Whitney test). The sensitivities, specificities
(receiver operating characteristic [ROC] curve analysis) and interobserver
correlation (intraclass coefficient, ICC) of quantitative HBP analysis were
determined. RESULTS: All FNH and 44.4% of HCA appeared hyper- or isointense
relative to the adjacent liver on qualitative HBP analysis. The mean SIR (P <
0.01) and LLCER (P < 0.0001) of FNH were significantly higher than that of HCA.
The area under the ROC curve for the differentiation of FNH from HCA with LLCER
was 0.98 for both observers. With a cutoff value of -0.3%-observer 1 with highest
experience- LLCER assessment provided respective sensitivity and specificity
values of 100% and 96.2% for the differentiation of FNH from HCA. The ICC was 0.7
for SIR measurements and 0.8 for LLCER measurements. CONCLUSION: Quantitative
LLCER assessment allows an accurate differentiation of FNH from HCA, even in
hyper- or isointense HCA on HBP images.
PMID- 25851030
TI - Growth rate hypothesis and efficiency of protein synthesis under different
sulphate concentrations in two green algae.
AB - The growth rate hypothesis (GRH) predicts a positive correlation between growth
rate and RNA content because growth depends upon the protein synthesis machinery.
The application of this hypothesis to photoautotrophic organisms has been
questioned. We tested the GRH on one prasinophycean, Tetraselmis suecica, and one
chlorophycean, Dunaliella salina, grown at three sulphate concentrations.
Sulphate was chosen because its concentration in the oceans increased through
geological time and apparently had a role in the evolutionary trajectories of
phytoplankton. Cell protein content and P quota were positively related to the
RNA content (r = 0.62 and r = 0.74, respectively). The correlation of the RNA
content with growth rates (r = 0.95) indicates that the GRH was valid for these
species when growth rates were below 0.82 d(-1) .
PMID- 25851031
TI - Patients' willingness to utilize a SMS-based appointment scheduling system at a
family practice unit in a developing country.
AB - Aim The investigators aimed to assess the willingness of patients to utilize and
pay for a proposed short message service- (SMS) based appointment scheduling
service. BACKGROUND: Telecommunication applications have been introduced to
improve the delivery of healthcare services in developed countries; however,
public-funded healthcare systems in developing countries like Nigeria are mostly
unfamiliar with the use of such technologies for improving healthcare access.
METHODS: We proposed a SMS-based (text message) appointment scheduling system to
consenting subjects at an outpatients' clinic and explored their willingness to
utilize and pay for the service. Using semi-structured interview schedules, we
collected information on: estimated arrival time, most important worry when
seeking for healthcare services at public hospitals in the study setting,
ownership of a mobile phone, willingness to utilize a SMS-based appointment for
clinic visits and willingness to pay for the service. In addition, respondents
were asked to suggest a tariff for the proposed system. Findings A total of 500
consecutively recruited patients aged 16-86 (42.1+/-15.4) years participated; 54%
(n=270) were females. Waiting time ranged from 1-7.5 h (3.9+/-1.1). Two
overlapping themes emerged as most important worries: crowded waiting rooms and
long waiting time. Ownership of mobile phones was reported by 96.4% (n=482) of
subjects. Nearly all favoured the proposed appointment scheduling system (n=486,
97.2%). Majority of patients who favoured the system were willing to pay for the
service (n=484, 99.6%). Suggested tariff ranged from 0.03 to 20.83 (1.53+/-2.11)
US dollars; 89.8% (n=349) of the subjects suggested tariffs that were greater
than the prevailing retail cost of the proposed service. In sum, our findings
indicate that patients in this study were willing to utilize and pay for a
proposed SMS-based appointment scheduling system. The findings have implications
for policies aimed at improving healthcare access and delivery of healthcare
services at the primary care level in developing countries like Nigeria.
PMID- 25851032
TI - Solubility prediction, solvate and cocrystal screening as tools for rational
crystal engineering.
AB - OBJECTIVES: The fact that novel drug candidates are becoming increasingly
insoluble is a major problem of current drug development. Computational tools may
address this issue by screening for suitable solvents or by identifying potential
novel cocrystal formers that increase bioavailability. In contrast to other more
specialized methods, the fluid phase thermodynamics approach COSMO-RS (conductor
like screening model for real solvents) allows for a comprehensive treatment of
drug solubility, solvate and cocrystal formation and many other thermodynamics
properties in liquids. This article gives an overview of recent COSMO-RS
developments that are of interest for drug development and contains several new
application examples for solubility prediction and solvate/cocrystal screening.
METHODS: For all property predictions COSMO-RS has been used. The basic concept
of COSMO-RS consists of using the screening charge density as computed from first
principles calculations in combination with fast statistical thermodynamics to
compute the chemical potential of a compound in solution. KEY FINDING: The fast
and accurate assessment of drug solubility and the identification of suitable
solvents, solvate or cocrystal formers is nowadays possible and may be used to
complement modern drug development. Efficiency is increased by avoiding costly
quantum-chemical computations using a database of previously computed molecular
fragments. SUMMARY: COSMO-RS theory can be applied to a range of physico-chemical
properties, which are of interest in rational crystal engineering. Most notably,
in combination with experimental reference data, accurate quantitative solubility
predictions in any solvent or solvent mixture are possible. Additionally, COSMO
RS can be extended to the prediction of cocrystal formation, which results in
considerable predictive accuracy concerning coformer screening. In a recent
variant costly quantum chemical calculations are avoided resulting in a
significant speed-up and ease-of-use.
PMID- 25851033
TI - A cAMP Biosensor-Based High-Throughput Screening Assay for Identification of Gs
Coupled GPCR Ligands and Phosphodiesterase Inhibitors.
AB - Cyclic adenosine 3',5'-monophosphate (cAMP) is an important second messenger, and
quantification of intracellular cAMP levels is essential in studies of G protein
coupled receptors (GPCRs). The intracellular cAMP levels are regulated by the
adenylate cyclase (AC) upon activation of either Gs- or Gi-coupled GPCRs, which
leads to increased or decreased cAMP levels, respectively. Here we describe a
real-time Forster resonance energy transfer (FRET)-based cAMP high-throughput
screening (HTS) assay for identification and characterization of Gs-coupled GPCR
ligands and phosphodiesterase (PDE) inhibitors in living cells. We used the beta2
adrenergic receptor (beta(2)AR) as a representative Gs-coupled receptor and
characterized two cell lines with different expression levels. Low receptor
expression allowed detection of desensitization kinetics and delineation of
partial agonism, whereas high receptor expression resulted in prolonged signaling
and enabled detection of weak partial agonists and/or ligands with low potency,
which is highly advantageous in large HTS settings and hit identification. In
addition, the assay enabled detection of beta(2)AR inverse agonists and PDE
inhibitors. High signal-to-noise ratios were also observed for the other
representative Gs-coupled GPCRs tested, GLP-1R and GlucagonR. The FRET-based cAMP
biosensor assay is robust, reproducible, and inexpensive with good Z factors and
is highly applicable for HTS.
PMID- 25851035
TI - Development of an HTS-Compatible Assay for the Discovery of Ulk1 Inhibitors.
AB - A rapidly accumulating body of work suggests the autophagy pathway is an
attractive therapeutic target for neurodegenerative diseases and cancer. To
validate autophagy as an anticancer strategy and to assess if systemic inhibition
of the pathway will have deleterious effects on normal tissues and physiology,
highly selective autophagy inhibitors are needed. While several inducers and
inhibitors of autophagy are known, all are nonspecific and none target the
enzymes that execute the pathway. A central upstream regulator of the autophagy
pathway is the serine/threonine kinase Ulk1 (UNC-51-like kinase-1). Selective
molecular probes that function as Ulk1-specific inhibitors are needed to improve
our understanding of the autophagy pathway. To identify inhibitors of Ulk1 kinase
activity, we developed an HTS-compatible, homogeneous biochemical assay using
AlphaScreen technology. This novel assay design uses purified stress-activated
Ulk1 and monitors phosphorylation of its full-length native substrate, Atg13.
This assay was optimized and validated in a 384-well format by screening the
Sigma LOPAC library. Here we report that the Ulk1 AlphaScreen assay is robust and
reproducible, with a Z' factor value of 0.83 +/- 0.02 and a signal to background
ratio of 20 +/- 1.2. Thus, this assay can be used to screen large chemical
libraries to discover novel inhibitors of Ulk1.
PMID- 25851034
TI - Electroporation Knows No Boundaries: The Use of Electrostimulation for siRNA
Delivery in Cells and Tissues.
AB - The discovery of RNA interference (RNAi) has enabled several breakthrough
discoveries in the area of functional genomics. The RNAi technology has emerged
as one of the major tools for drug target identification and has been steadily
improved to allow gene manipulation in cell lines, tissues, and whole organisms.
One of the major hurdles for the use of RNAi in high-throughput screening has
been delivery to cells and tissues. Some cell types are refractory to high
efficiency transfection with standard methods such as lipofection or calcium
phosphate precipitation and require different means. Electroporation is a
powerful and versatile method for delivery of RNA, DNA, peptides, and small
molecules into cell lines and primary cells, as well as whole tissues and
organisms. Of particular interest is the use of electroporation for delivery of
small interfering RNA oligonucleotides and clustered regularly interspaced short
palindromic repeats/Cas9 plasmid vectors in high-throughput screening and for
therapeutic applications. Here, we will review the use of electroporation in high
throughput screening in cell lines and tissues.
PMID- 25851036
TI - A Screening Assay Cascade to Identify and Characterize Novel Selective Estrogen
Receptor Downregulators (SERDs).
AB - Here, we describe an approach to identify novel selective estrogen receptor
downregulator (SERD) compounds with improved properties such as oral
bioavailability and the potential of increased efficacy compared to currently
marketed drug treatments. Previously, methodologies such as Western blotting and
transient cell reporter assays have been used to identify and characterize SERD
compounds, but such approaches can be limited due to low throughput and
sensitivity, respectively. We have used an endogenous cell-imaging strategy that
has both the throughput and sensitivity to support a large-scale hit-to-lead
program to identify novel compounds. A screening cascade with a suite of assays
has been developed to characterize compounds that modulate estrogen receptor
alpha (ERalpha)-mediated signaling or downregulate ERalpha levels in cells.
Initially, from a focused high-throughput screening, novel ERalpha binders were
identified that could be modified chemically into ERalpha downregulators.
Following this, cellular assays helped determine the mechanism of action of
compounds to distinguish between on-target and off-target compounds and
differentiate SERDs, selective estrogen receptor modulator (SERM) compounds, and
agonist ERalpha ligands. Data are shown to exemplify the characterization of
ERalpha-mediated signaling inhibitors using a selection of literature compounds
and illustrate how this cascade has been used to drive the chemical design of
novel SERD compounds.
PMID- 25851038
TI - Pulsed microdischarge with inductively coupled plasma mass spectrometry for
elemental analysis on solid metal samples.
AB - Pulsed microdischarge employed as source for direct solid analysis was
investigated in N2 environment at atmospheric pressure. Compared with direct
current (DC) microdischarge, it exhibits advantages with respect to the ablation
and emission of the sample. Comprehensive evidence, including voltage-current
relationship, current density (j), and electron density (ne), suggests that
pulsed microdischarge is in the arc regime while DC microdischarge belongs to
glow. Capability in ablating metal samples demonstrates that pulsed
microdischarge is a viable option for direct solid sampling because of the
enhanced instantaneous energy. Using optical spectrometer, only common emission
lines of N2 can be acquired in DC mode, whereas primary atomic and ionic lines of
the sample are obtained in the case of pulsed mode. Calculations show a
significant difference in N2 vibrational temperatures between DC and pulsed
microdischarge. Combined with inductively coupled plasma mass spectrometry
(ICPMS), pulsed microdischarge exhibits much better performances in calibration
linearity and limits of detection (LOD) than those of DC discharge in direct
analysis of samples of different matrices. To improve transmission efficiency, a
mixture of Ar and N2 was employed as discharge gas as well as carrier gas in
follow-up experiments, facilitating that LODs of most elements reached ng/g.
PMID- 25851037
TI - A Quantitative Microtiter Assay for Sialylated Glycoform Analyses Using Lectin
Complexes.
AB - Fidelity of glycan structures is a key requirement for biotherapeutics, with
carbohydrates playing an important role for therapeutic efficacy. Comprehensive
glycan profiling techniques such as liquid chromatography (LC) and mass
spectrometry (MS), while providing detailed description of glycan structures,
require glycan cleavage, labeling, and paradigms to deconvolute the considerable
data sets they generate. On the other hand, lectins as probes on microarrays have
recently been used in orthogonal approaches for in situ glycoprofiling but
require analyte labeling to take advantage of the capabilities of automated
microarray readers and data analysis they afford. Herein, we describe a lectin
based microtiter assay (lectin-enzyme-linked immunosorbent assay [ELISA]) to
quantify terminal glycan moieties, applicable to in vitro and in-cell glycan
engineered Fc proteins as well as intact IgGs from intravenous immunoglobulin
(IVIG), a blood product containing pooled polyvalent IgG antibodies extracted
from plasma from healthy human donors. We corroborate our findings with industry
standard LC-MS profiling. This "customizable" ELISA juxtaposes readouts from
multiple lectins, focusing on a subset of glycoforms, and provides the ability to
discern single- versus dual-arm glycosylation while defining levels of epitopes
at sensitivities comparable to MS. Extendable to other biologics, this ELISA can
be used stand-alone or complementary to MS for quantitative glycan analysis.
PMID- 25851039
TI - Cytotoxicity evaluation of polymer-derived ceramics for pacemaker electrode
applications.
AB - Ceramics are known to be chemically stable, and the possibility to electrically
dope polymer-derived ceramics makes it a material of interest for implantable
electrode applications. We investigated cytotoxic characteristics of four polymer
derived ceramic candidates with either electrically conductive or insulating
properties. Cytotoxicity was assessed by culturing C2C12 myoblast cells under two
conditions: by exposing them to material extracts and by putting them directly in
contact with material samples. Cell spreading was optically evaluated by
comparing microscope observations immediately after the materials insertion and
after 24 h culturing. Cell viability (MTT) and mortality (LDH) were quantified
after 24-h incubation in contact with the materials. Comparison was made with
biocompatible positive references (alumina, platinum, biocompatible stainless
steel 1.4435), negative references (latex, stainless steel 1.4301) and controls
(no material present in the culture wells). We found that the cytotoxic
properties of tested ceramics are comparable to established reference materials.
These ceramics, which are reported to be very stable, can be microstructured and
electrically doped to a wide range of conductivity and are thus excellent
candidates for implantable electrode applications including pacemakers.
PMID- 25851040
TI - Combined accurate platelet enumeration and reticulated platelet determination by
flow cytometry.
AB - BACKGROUND: Diagnosing the cause of thrombocytopenia often requires a bone marrow
aspiration or biopsy, an invasive procedure. Reticulated platelets (RP) are
immature RNA containing platelets, accurate RP enumeration has yet to be
achieved, partially due to the lack of a robust reference method. GOAL: To refine
previous work and gating strategies distinguishing RP from mature platelets while
incorporating accurate platelet enumeration into the analysis. After reviewing
previously published studies on Thiazole Orange (TO) staining of RP, we
systematically evaluated CD41/CD61 in combination with a commercial source of TO
(BDBiosciences). Previous RP methods have not taken advantage of platelet
enumeration therefore our goal was to incorporate the ICSH platelet enumeration
protocol into our method. METHODS: TO concentration, incubation, and fixation
method were determined to be 10% of stock concentration, 30 min, and 1%
formaldehyde respectively. Gating strategy to determine RP fraction used an
unstained control tube to set the limit of TO staining. RESULTS: Normal range (n
= 51) was 9.9 +/- 3.1%. Analysis of 40 patients with immune-thrombocytopenia
purpura (ITP) showed a RP range from 4.3% to 81.2%. Platelet enumeration was
consistent with our previous studies in this area. CONCLUSIONS: Combining
CD41/CD61 platelet enumeration with TO RP percentage is possible. Accurate RP
percentage requires an effective gating strategy, as background fluorescence
cursor placement is important. This method for enumeration of RP percentage
combined with accurate platelet enumeration, particularly in the low range,
should prove useful in differentiating production from consumption issues in
thrombocytopenia and monitoring response to therapy.
PMID- 25851041
TI - Biotin[6]uril Esters: Chloride-Selective Transmembrane Anion Carriers Employing C
H...Anion Interactions.
AB - Biotin[6]uril hexaesters represent a new class of anionophores which operate
solely through C-H...anion interactions. The use of soft H-bond donors favors the
transport of less hydrophilic anions (e.g., Cl(-), NO3(-)) over hard, stongly
hydrated anions (e.g., HCO3(-) and SO4(2-)). Especially relevant is the
selectivity between chloride and bicarbonate, the major inorganic anions in
biological systems.
PMID- 25851046
TI - Misclassification of iodine intake level from morning spot urine samples with
high iodine excretion among Inuit and non-Inuit in Greenland.
AB - Iodine nutrition is commonly assessed from iodine excretion in urine. A 24 h
urine sample is ideal, but it is cumbersome and inconvenient. Hence, spot urine
samples with creatinine to adjust for differences in void volume are widely used.
Still, the importance of ethnicity and the timing of spot urine samples need to
be settled. We, thus, collected 104 early morning spot urine samples and 24 h
urine samples from Inuit and non-Inuit living in Greenland. Diet was assessed by
a FFQ. Demographic data were collected from the national registry and by
questionnaires. Iodine was measured using the Sandell-Kolthoff reaction,
creatinine using the Jaffe method and para-amino benzoic acid by the HPLC method
for the estimation of completeness of urine sampling and compensation of
incomplete urine samples to 24 h excretion. A population-based recruitment was
done from the capital city, a major town and a settlement (n 36/48/20).
Participants were seventy-eight Inuit and twenty-six non-Inuit. The median 24 h
iodine excretion was 138 (25th-75th percentile 89-225) MUg/97 (25th-75th
percentile 72-124) MUg in Inuit/non-Inuit (P= 0.030), and 153 (25th-75th
percentile 97-251) MUg/102 (25th-75th percentile 73-138) MUg (P= 0.026) when
including compensated iodine excretion. Iodine excretion in 24 h urine samples
increased with a rising intake of traditional Inuit foods (P= 0.005). Iodine
excretion was lower in morning spot urine samples than in 24 h urine samples (P<
0.001). This difference was associated with iodine intake levels (P< 0.001), and
was statistically significant when the iodine excretion level was above 150
MUg/24 h. In conclusion, the iodine intake level was underestimated from morning
spot urine samples if iodine excretion was above the recommended level.
PMID- 25851047
TI - Concise Review: Prospects of Bone Marrow Mononuclear Cells and Mesenchymal Stem
Cells for Treating Status Epilepticus and Chronic Epilepsy.
AB - Mononuclear cells (MNCs) and mesenchymal stem cells (MSCs) derived from the bone
marrow and other sources have received significant attention as donor cells for
treating various neurological disorders due to their robust neuroprotective and
anti-inflammatory effects. Moreover, it is relatively easy to procure these cells
from both autogenic and allogenic sources. Currently, there is considerable
interest in examining the usefulness of these cells for conditions such as status
epilepticus (SE) and chronic epilepsy. A prolonged seizure activity in SE
triggers neurodegeneration in the limbic brain areas, which elicits
epileptogenesis and evolves into a chronic epileptic state. Because of their
potential for providing neuroprotection, diminishing inflammation and curbing
epileptogenesis, early intervention with MNCs or MSCs appears attractive for
treating SE as such effects may restrain the development of chronic epilepsy
typified by spontaneous seizures and learning and memory impairments. Delayed
administration of these cells after SE may also be useful for easing spontaneous
seizures and cognitive dysfunction in chronic epilepsy. This concise review
evaluates the current knowledge and outlook pertaining to MNC and MSC therapies
for SE and chronic epilepsy. In the first section, the behavior of these cells in
animal models of SE and their efficacy to restrain neurodegeneration,
inflammation, and epileptogenesis are discussed. The competence of these cells
for suppressing seizures and improving cognitive function in chronic epilepsy are
conferred in the next section. The final segment ponders issues that need to be
addressed to pave the way for clinical application of these cells for SE and
chronic epilepsy.
PMID- 25851048
TI - Duchenne muscular dystrophy diagnostics: it only gets better but some of the same
challenges remain.
PMID- 25851049
TI - Estimating Protistan Diversity Using High-Throughput Sequencing.
AB - Sequencing hypervariable regions from the 18S rRNA gene is commonly employed to
characterize protistan biodiversity, yet there are concerns that short reads do
not provide the same taxonomic resolution as full-length sequences. A total of
7,432 full-length sequences were used to perform an in silico analysis of how
sequences of various lengths and target regions impact downstream ecological
interpretations. Sequences that were longer than 400 nucleotides and included the
V4 hypervariable region generated results similar to those derived from full
length 18S rRNA gene sequences. Present high-throughput sequencing capabilities
are approaching protistan diversity estimation comparable to whole gene
sequences.
PMID- 25851050
TI - 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of
Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care
(Endorsed by the American Heart Association, the Cardiological Society of India,
and Sociedad Latino Americana de Cardiologia Intervencion; Affirmation of Value
by the Canadian Association of Interventional Cardiology-Association Canadienne
de Cardiologie D'intervention).
AB - Although historically the intra-aortic balloon pump has been the only mechanical
circulatory support device available to clinicians, a number of new devices have
become commercially available and have entered clinical practice. These include
axial flow pumps, such as Impella(r); left atrial to femoral artery bypass pumps,
specifically the TandemHeart; and new devices for institution of extracorporeal
membrane oxygenation. These devices differ significantly in their hemodynamic
effects, insertion, monitoring, and clinical applicability. This document reviews
the physiologic impact on the circulation of these devices and their use in
specific clinical situations. These situations include patients undergoing high
risk percutaneous coronary intervention, those presenting with cardiogenic shock,
and acute decompensated heart failure. Specialized uses for right-sided support
and in pediatric populations are discussed and the clinical utility of mechanical
circulatory support devices is reviewed, as are the American College of
Cardiology/American Heart Association clinical practice guidelines.
PMID- 25851051
TI - Optimization and automation of an end-to-end high throughput microscale transient
protein production process.
AB - High throughput protein production from transient transfection of mammalian cells
is used in multiple facets of research and development studies. Commonly used
formats for these high number expressions are 12-, 24- and 96-well plates at
various volumes. However there are no published examples of a 96-deep well plate
microscale (1,000 MUL) suspension process for mammalian transient expression. For
this reason, we aimed to determine the optimal operating conditions for a high
producing, microscale HEK293 transient system. We evaluated the hydrodynamic flow
and measured the oxygen transfer rate (OTR) and transient protein expression for
96-deep well plates of different well geometries filled at 600-1,000 MUL working
volumes and agitated at various speeds and orbital diameters. Ultimately, a round
well-round bottom (RR) 96-deep well plate with a working volume of 1,000 uL
agitated at 1,000 RPM and a 3 mm orbital diameter yielded the highest and most
consistent total transient protein production. As plate cultures are subject to
evaporation, water loss from different plate seals was measured to identify an
optimal plate sealing method. Finally, to enable higher capacity protein
production, both expression and purification processes were automated.
Functionality of this end-to-end automation workflow was demonstrated with the
generation of high levels of human IgG1 antibodies (>=360 ug/mL) with
reproducible productivity, product quality and >=78% purification recovery.
PMID- 25851053
TI - [Endoscopy of the Lacrimal Duct System in Children].
AB - BACKGROUND: Pathologies of the lacrimal duct system show a frequent occurrence in
paediatric ophthalmology. Mostly, the connection between the nasolacrimal duct
and the nose fails to open but also combined diseases or congenital anomalies may
be the reason. Because of complications, the chance for healing after a
conservative therapeutic approach decreases and surgical intervention is
necessary. PATIENTS AND METHODS: The opportunity for transcanalicular endoscopy
of the lacrimal duct system in children is shown by the presentation of three
different case reports. Typical clinical findings are given and the use of
dacryoendoscopy for diagnostic and therapeutic benefit is pointed out. Therefore,
we present an 8-week-old child, suffering recurrent purulent inflammation due to
an amniotocele (1), a 5-year-old child having a congenital lacrimal fistula (2)
and another 5-year-old child with a severe chronic dacryocystitis of both eyes
after several lacrimal duct surgeries showing remaining intrasaccal silicone
tubes (3). RESULTS: In all these cases transcanalicular endoscopy could be used
successfully for reconstruction of the lacrimal duct systems. A bullous Hasner's
membrane could be localized and opened (1). The lacrimal fistula was identified
to communicate with the common canaliculus and combined stenosis of the
canaliculus and saccus were treated (2). In the third case fragments of
intrasaccal silicone tubes could be localised and the foreign bodies could be
evacuated by transcanalicular surgery (3). The children with lacrimal fistula and
the intrasaccal foreign bodies were treated with self-threading silicone tubing
which was removed three months later. In the follow-up period (16 months in case
2, 22 months in case 3 and 38 months in case 1) recurrences of the lacrimal
pathologies or clinical complaints were absent. CONCLUSION: Transcanalicular
endoscopy of the lacrimal duct system should not be regarded as the means of
choice but it does offer additional diagnostic and therapeutic options for
special indications. A main advantage of this kind of surgery is its minimally
invasive character. Under visual control, topographic anatomy can be preserved.
Dacryoendoscopy in children should be done only by experienced surgeons.
PMID- 25851052
TI - Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to
infant transmission of hepatitis B virus.
AB - The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in
reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly
understood. We conducted a prospective, multicenter trial and enrolled 118
hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant
women with HBV DNA >=7.5 log10 IU/mL. The mothers received no medication (control
group, n = 56, HBV DNA 8.22 +/- 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group,
n = 62, HBV DNA 8.18 +/- 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1
month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery,
the TDF group had lower maternal HBV DNA levels (4.29 +/- 0.93 versus 8.10 +/-
0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower
rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg
positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate
analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P =
0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P =
0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal
alanine aminotransferase (ALT) levels above two times the upper limit of normal
for >=3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum
elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper
limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum.
Maternal creatinine and creatinine kinase levels, rates of congenital anomaly,
premature birth, and growth parameters in infants were comparable in both groups.
At 12 months, one TDF-group child newly developed HBsAg positivity, presumably
due to postnatal infection and inefficient humoral responses to vaccines.
CONCLUSIONS: Treatment with TDF for highly viremic mothers decreased infant HBV
DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT
elevations. (Hepatology 2015;62:375-386.
PMID- 25851055
TI - Reagent pencils: a new technique for solvent-free deposition of reagents onto
paper-based microfluidic devices.
AB - Custom-made pencils containing reagents dispersed in a solid matrix were
developed to enable rapid and solvent-free deposition of reagents onto membrane
based fluidic devices. The technique is as simple as drawing with the reagent
pencils on a device. When aqueous samples are added to the device, the reagents
dissolve from the pencil matrix and become available to react with analytes in
the sample. Colorimetric glucose assays conducted on devices prepared using
reagent pencils had comparable accuracy and precision to assays conducted on
conventional devices prepared with reagents deposited from solution. Most
importantly, sensitive reagents, such as enzymes, are stable in the pencils under
ambient conditions, and no significant decrease in the activity of the enzyme
horseradish peroxidase stored in a pencil was observed after 63 days. Reagent
pencils offer a new option for preparing and customizing diagnostic tests at the
point of care without the need for specialized equipment.
PMID- 25851054
TI - Overexpression of Nrf2 attenuates Carmustine-induced cytotoxicity in U87MG human
glioma cells.
AB - BACKGROUND: Malignant glioma is one of the most devastating tumors in adults with
poor patient prognosis. Notably, glioma often exhibits resistance to conventional
chemotherapeutic approaches, complicating patient treatments. However, the
molecular mediators involved in tumor chemoresistance remain poorly defined,
creating a barrier to the successful management of glioma. In the present study,
we hypothesized that the antioxidant transcription factor, Nrf2 (nuclear factor
erythroid-derived 2 like 2), attenuates glioma cytotoxicity to Carmustine (BCNU),
a widely used chemotherapeutic agent known to modulate cellular oxidative
balance. METHODS: To test the hypothesis, we employed human malignant glioma cell
line, U87MG and overexpression of Nrf2 in glioma cells was achieved using both
pharmacological and genetic approaches. RESULTS: Notably, induction of Nrf2 was
associated with increased expression of heme oxygenase-1 (HO-1), a stress
inducible enzyme involved in anti-oxidant defense. In addition, over expression
of Nrf2 in U87MG cells significantly attenuated the cytotoxicity of Carmustine as
evidenced by both cellular viability assay and flow cytometry analysis.
Consistent with this, antioxidants such as glutathione and N-acetyl cysteine
significantly reduced Carmustine mediated glioma cytotoxicity. CONCLUSIONS: Taken
together, these data strongly implicate an unexplored role of Nrf2 in glioma
resistance to Carmustine and raise the possible use of Nrf2 inhibitors as adjunct
to Carmustine for the treatment of malignant glioma.
PMID- 25851056
TI - Predictive classification of correlated targets with application to detection of
metastatic cancer using functional CT imaging.
AB - Perfusion computed tomography (CTp) is an emerging functional imaging modality
that uses physiological models to quantify characteristics pertaining to the
passage of fluid through blood vessels. Perfusion characteristics provide
physiological correlates for neovascularization induced by tumor angiogenesis.
Thus CTp offers promise as a non-invasive quantitative functional imaging tool
for cancer detection, prognostication, and treatment monitoring. In this article,
we develop a Bayesian probabilistic framework for simultaneous supervised
classification of multivariate correlated objects using separable covariance. The
classification approach is applied to discriminate between regions of liver that
contain pathologically verified metastases from normal liver tissue using five
perfusion characteristics. The hepatic regions tend to be highly correlated due
to common vasculature. We demonstrate that simultaneous Bayesian classification
yields dramatic improvements in performance in the presence of strong correlation
among intra-subject units, yet remains competitive with classical methods in the
presence of weak or no correlation.
PMID- 25851057
TI - The interaction between self-bias and reward: Evidence for common and distinct
processes.
AB - The perceptual matching of shapes and labels can be affected by both self- and
reward-biases when shapes are linked either to labels referring to particular
individuals (you, friend, stranger) or to different reward values (L8, L2, L0).
We investigated the relations between these biases by varying the reward value
associated with particular shape-label pairs (circle-you, square-friend, triangle
stranger). Self shape-label pairs (circle-you) always received no reward, while
friend shape-label pairs (square-friend) received high reward and stranger shape
label pairs low reward (triangle-stranger), or the reverse (friend-low reward;
stranger-high reward). Despite receiving no reward, responses to self-related
pairs were advantaged relative to those to low-reward stimuli and did not differ
from those to high-reward items. There was also an advantage for responses to
high-reward friend pairs relative to low-reward stranger stimuli, and for high
reward stranger stimuli compared to low-reward friends. Correlations across
individuals were found across trial blocks for both the self-advantage and the
high-reward advantage, but the self- and reward-advantages were uncorrelated.
This suggests that the self- and reward-advantage effects have different origins.
In addition, the magnitude of the self-advantage varied according to the rated
personal distance between a participant and a stranger. For individuals
manifesting a close personal distance to strangers, the self-advantage was
smaller, and sensitivity to reward influenced the difference between the self-
and high-reward conditions. For individuals manifesting a large personal distance
to strangers, sensitivity to reward did not affect self-matching. We suggest that
self-advantages on perceptual matching arise independent of reward for
individuals with a large personal distance to strangers. On the other hand, in
individuals with a weak self-bias, high reward and the self modulate a common
subjective value system.
PMID- 25851058
TI - Remote surveillance after colorectal cancer surgery: an effective alternative to
standard clinic-based follow-up.
AB - AIM: Most colorectal cancer recurrences are asymptomatic and are detected through
routine postoperative clinic surveillance programmes with associated
investigations. However, attendance at these clinics has a financial cost and may
be associated with an increase in patient anxiety and dissatisfaction. The
results of a remote follow-up system developed for selected patients are
reported. METHOD: A remote surveillance programme has been in place in our
institution for over 9 years. Patients having elective and emergency treatment
for colorectal cancer were enrolled. The timeliness of the investigation,
detection of local recurrence and distant metastases and overall 5-year survival
rates were determined. A cost review and patient satisfaction survey were
performed. RESULTS: The programme was suitable for over 900 patients who had
received surgery for colorectal cancer between 2004 and 2012, representing some
50% of the total number of patients treated in this period. Of these, 811 (90%)
had investigations carried out on time. Five-year survival rates were comparable
with national data. Cost-minimization analysis demonstrated a financial saving of
63% and a 75% reduction in clinic appointments. High levels of overall patient
satisfaction (97%) were noted with the programme. CONCLUSION: A remote
surveillance system after colorectal cancer surgery is a safe and cost-effective
alternative to traditional clinic-based follow up and has high patient
satisfaction.
PMID- 25851059
TI - Efficacy of 1% acetic acid in the treatment of chronic wounds infected with
Pseudomonas aeruginosa: prospective randomised controlled clinical trial.
AB - : Chronic wounds are those wounds that are persistent and do not respond to any
sort of treatment. The concept of using topical antiseptics on open wounds is to
prevent and treat infections. They also help to shorten the time taken to heal
the wounds. The use of topical agents on wounds to prevent infection is a minimal
ability to develop resistance to the microorganisms. Pseudomonas aeruginosa is a
Gram-negative opportunistic pathogen with innate resistance to many antibiotics.
In places that are economically backward, these problems get compounded by the
inability of patients to afford newer expensive drugs. Topically applied dilute
acetic acid, which is cheap and easily available, has been found to be effective
in such chronic wounds. In the present study, an attempt has been made to use 1%
acetic acid as the sole antimicrobial agent for the treatment of pseudomonal
wound infections. A control limb was used in which the wounds were treated with
normal saline. Our objective was to evaluate the efficacy of acetic acid in low
concentration of 1% in chronic wounds infected with P. aeruginosa. This was a
prospective study conducted over a period of 6 months. INCLUSION CRITERIA: All
patients with chronic wounds infected with P. aeruginosa. EXCLUSION CRITERIA:
Wounds due to massive burns, suspected malignancy, immunocompromised individuals
and individuals with sepsis. A total of 32 patients enrolled in the study.
Subjects were randomised equally to the 1% acetic acid group and saline dressing
group. None of the patients received any systemic antibiotics during the study
period and received twice daily dressings. The endpoint of the treatment was
wounds free of P. aeruginosa. The duration of treatment required to eliminate the
Pseudomonas from the wounds in the acetic acid group was on an average 7 days
less than that required by the saline group. P value was <0.001. In the 1% acetic
acid group irrespective of the sensitivity of the organism to antibiotics,
Pseudomonas organisms were eliminated within the same time period - 4.5 days. In
the saline group, susceptible organisms were eliminated within 11.5 days and
multidrug-resistant organisms were eliminated by 15.5 days. 1% acetic acid is a
simple, safe and effective topical antiseptic that can be used in the elimination
of P. aeruginosa from chronic infected wounds.
PMID- 25851060
TI - Safety and immunogenicity of a soluble native Neospora caninum tachyzoite-extract
vaccine formulated with a soy lecithin/beta-glucan adjuvant in pregnant cattle.
AB - The global economic impact of Neospora caninum infection in cattle herds has
promoted the development of vaccines that can be safely used during pregnancy.
The aim of this study was to evaluate the safety and immunogenicity of a vaccine
formulated with the soluble fraction of tachyzoite's lysate and a soy-based
aqueous adjuvant (sNcAg/AVEC), which was protective in the mouse model and
induced strong IFN-gamma responses and high avidity antibodies in non-pregnant
cattle. Ten pregnant heifers were vaccinated twice during the first trimester of
gestation and 8 remained unvaccinated. Anti-N. caninum immune responses were
efficiently primed by vaccination, evidenced by a quick induction of IgM serum
titers (7dpv) and a prompt switch to high avidity IgG shortly after infection
(performed at 78 or 225 days of gestation; n=5 each); while naive cattle elicited
lower IgG titers, with a delayed kinetics. High systemic IFN-gamma levels were
induced after infection which did not interfere with pregnancy. No local or
systemic adverse effects were recorded along the study. Calves were born in term
and in good health conditions, showing that the sNcAg/AVEC vaccine was safe when
applied to healthy heifers during the first trimester of gestation.
PMID- 25851062
TI - Shortened length of hospital stay with rivaroxaban in patients with symptomatic
venous thromboembolism in Japan: the J-EINSTEIN pulmonary embolism and deep vein
thrombosis program.
AB - BACKGROUND: In Japan, the standard of care for the treatment of pulmonary
embolism (PE) and/or deep vein thrombosis (DVT) consists of intravenous
unfractionated heparin (UFH) followed by warfarin, which was recently compared
with rivaroxaban, an oral factor Xa inhibitor, in randomized trials. AIM: To
examine the length of hospital stay in patients with PE and/or DVT receiving
rivaroxaban compared to Japanese standard therapy in the Japanese (J)-EINSTEIN PE
and DVT program. METHODS: Open-label, randomized clinical trials that compared 3,
6, or 12 months of rivaroxaban with UFH and warfarin in patients with acute,
confirmed symptomatic proximal PE and/or DVT. Decisions regarding hospital
admission and/or discharge were left to the clinical judgment of attending
physicians. Analyses were conducted in the intention-to-treat (ITT) population.
RESULTS: In the ITT population (N = 97), overall patient characteristics were
similar in both treatment arms. The median length of stay in rivaroxaban patients
was 10.0 days (interquartile range [IQR] 6.0 to 15.0 days) while it was 15.0 days
(IQR 9.0 to 22.0) for patients on standard therapy (p = 0.016). All of the four
DVT patients who were not hospitalized for the index event were in the
rivaroxaban arm. CONCLUSIONS: Our results suggest that treatment with rivaroxaban
may significantly reduce the length of hospital stay in patients hospitalized for
PE and/or DVT compared with the current standard of care in Japan, thereby
reducing the burden on patients and the healthcare system. The limitations of our
study include small sample size and the generalizability of the findings to the
real-world setting. Further research is warranted to identify PE and/or DVT
patients in Japanese clinical practice who may potentially be managed as
outpatients. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01516814 and NCT01516840.
PMID- 25851063
TI - Persistent topology for cryo-EM data analysis.
AB - In this work, we introduce persistent homology for the analysis of cryo-electron
microscopy (cryo-EM) density maps. We identify the topological fingerprint or
topological signature of noise, which is widespread in cryo-EM data. For low
signal-to-noise ratio (SNR) volumetric data, intrinsic topological features of
biomolecular structures are indistinguishable from noise. To remove noise, we
employ geometric flows that are found to preserve the intrinsic topological
fingerprints of cryo-EM structures and diminish the topological signature of
noise. In particular, persistent homology enables us to visualize the gradual
separation of the topological fingerprints of cryo-EM structures from those of
noise during the denoising process, which gives rise to a practical procedure for
prescribing a noise threshold to extract cryo-EM structure information from noise
contaminated data after certain iterations of the geometric flow equation. To
further demonstrate the utility of persistent homology for cryo-EM data analysis,
we consider a microtubule intermediate structure Electron Microscopy Data (EMD
1129). Three helix models, an alpha-tubulin monomer model, an alpha-tubulin and
beta-tubulin model, and an alpha-tubulin and beta-tubulin dimer model, are
constructed to fit the cryo-EM data. The least square fitting leads to similarly
high correlation coefficients, which indicates that structure determination via
optimization is an ill-posed inverse problem. However, these models have
dramatically different topological fingerprints. Especially, linkages or
connectivities that discriminate one model from another, play little role in the
traditional density fitting or optimization but are very sensitive and crucial to
topological fingerprints. The intrinsic topological features of the microtubule
data are identified after topological denoising. By a comparison of the
topological fingerprints of the original data and those of three models, we found
that the third model is topologically favored. The present work offers persistent
homology based new strategies for topological denoising and for resolving ill
posed inverse problems.
PMID- 25851064
TI - Polycyclic aromatic hydrocarbon concentrations in gas and particle phases and
source determination in atmospheric samples from a semiurban area of Dourados,
Brazil.
AB - A headspace solid-phase microextraction (HS-SPME) procedure that employs a
PDMS/DVB fiber was developed for the analysis of gas-phase polycyclic aromatic
hydrocarbons (PAHs) collected in polyurethane foam (PUF) by gas chromatography
(GC) mass spectrometry. The method exhibited good linearity (R (2) > 0.99) and
repeatability (4.9-25 %) as well as an impressive detection limit that ranged
from 1.1 to 3.3 ng. Twenty-two air samples were collected by high-volume samplers
from January to November 2007 in a semiurban area of Dourados (Brazil) and were
analyzed for their content of total suspended particulates and PAHs. The PAHs
were extracted from the PUF samples using the developed procedure (HS-SPME), and
PAHs adsorbed on particulate matter were extracted with dichloromethane/methanol
(4:1 [v/v]) in an ultrasonic bath. The values of the total daily concentrations
of 16 PAHs determined in the samples ranged from 0.375 to 8.407 ng m(-3). In
addition, diagnostic ratios were calculated, showing that the PAHs in the
atmosphere at the sampling site originated predominantly from vehicle emissions
and the combustion of grass and wood. Hierarchical cluster analysis and principal
component analysis were performed as well, the results of which indicated (1) the
same sources of PAH identified by the diagnostic ratios and (2) that the sampling
days could be categorized into three groups depending on the atmospheric
conditions. GC retention indices were also used to identify PAHs, biphenyl
(phenylbenzene), and heterocyclic organic compounds (benzofurans) in some of the
samples.
PMID- 25851065
TI - Research Synthesis and the Value per Statistical Life.
AB - The value of small changes in mortality risk, conventionally expressed as the
value per statistical life (VSL), is a major determinant of the benefits of many
environmental, health, and safety regulations and other policies. However,
selecting an appropriate value is challenging. Different studies yield different
results and analysts often find they lack estimates that are directly applicable
to the policy they are assessing. Research-synthesis methods are widely used to
address these concerns in many fields, yet we find only limited applications to
estimating VSL. More structured, criteria-driven review of the available studies
is an important first step. Additional meta-analyses that use such review as a
starting point are needed to explore variation across studies as well as to
adjust estimates to better fit different policy contexts. Carefully designed
expert elicitation is significantly underutilized and is particularly important
when the available research is limited or inconsistent. Although greater use of
such methods is likely to enhance the credibility of the VSL estimates applied in
policy analyses, as well as provide greater insights into the advantages and
limitations of the available research, it is not clear how much the resulting
estimates will vary from those currently used. In the United States, these
estimates are generally around $9 million.
PMID- 25851066
TI - The BMJ report on mortality cuts in hospitals put into special measures in 2013
is misleading.
PMID- 25851067
TI - Bio-inspired artificial functional photocatalyst: biomimetic enzyme-like
TiO2/reduced graphene oxide nanocomposite with excellent molecular recognition
ability.
AB - An enzyme-like TiO(2)/reduced graphene oxide (enzyme-TiO(2)/rGO) nanocomposite
with molecular recognition ability was fabricated by biomimicking the geometrical
and chemical complementation of the enzyme and substrate. The anatase TiO(2)
nanocrystals were densely dispersed on rGO nanosheets with close interfacial
contacts. With geometrical and chemical matching of target molecules and
memorized cavities, the adsorption capacity of enzyme-TiO(2)/rGO nanocomposites
for 4-nitrophenol (4.71 mg g(-1)) is about six times that of control TiO(2)/rGO
without the enzyme-like feature (0.79 mg g(-1)), and the enzyme-TiO(2)/rGO shows
a relative selectivity coefficient of 7.24. Moreover, enzyme-TiO(2)/rGO exhibits
molecular recognitive photocatalytic degradation for a particular contaminant.
The results demonstrate that enzyme-substrate recognition provides a convenient
and powerful basis on which to biomimic and construct efficient photocatalysts
with high selectivity.
PMID- 25851068
TI - Cytoprotective and Anti-secretory Effects of Azadiradione Isolated from the Seeds
of Azadirachta indica (neem) on Gastric Ulcers in Rat Models.
AB - Azadirachta indica is well known medicinal plant mentioned in ancient herbal
texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine
and has become a luminary of modern medicine. As part of our drug discovery
program we isolated azadiradione from the ethanolic extract of seeds of A. indica
and evaluated for in-vivo antiulcer activity in cold restraint induced gastric
ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers
model and pyloric ligation induced ulcer model. Azadiradione exhibited potent
antiulcer activity through the inhibition of H+ K+-ATPase (proton pump) activity
via its cytoprotective effect and also via its antisecretory effect. This
combined effect has valuable potential in the future treatment of peptic
ulceration.
PMID- 25851069
TI - Increased Prevalence and Resistance of Important Pathogens Recovered from
Respiratory Specimens of Cystic Fibrosis Patients During a Decade.
AB - BACKGROUND: The study objective was to identify changes of prevalence and
resistance of important pathogens in specimens of cystic fibrosis (CF) patients
within a decade. METHODS: Samples of 94 patients, who attended 2 CF centers from
2001 to 2011 were retrospectively analyzed. RESULTS: Staphylococcus aureus was
the most prevalent organism (74.5% in 2011) with an increase of methicillin
resistant S. aureus in patients (0% vs. 9.6%, n = 9). Resistance of S. aureus to
gentamicin decreased (41.8% vs. 21%; P < 0.001), whereas resistance to rifampicin
and trimethoprim/sulfamethoxazole (P < 0.05) increased significantly with a trend
to increased resistance to clindamycin and erythromycin (P = 0.063). Methicillin
resistant S. aureus isolates belonged to 6 spa types (t003, t008, t011, t034,
t045, t548). There was a significant increase of Pseudomonas aeruginosa
prevalence (63.8% in 2011 vs. 46.8% in 2001, P = 0.019). Resistance of P.
aeruginosa increased significantly to imipenem, gentamicin, amikacin, tobramycin,
ciprofloxacin and fosfomycin, whereas resistance to piperacillin-tazobactam,
meropenem and aztreonam decreased. Significantly fewer Stenotrophomonas
maltophilia isolates were susceptible to all the analyzed antibiotics
(trimethoprim/sulfamethoxazole, ciprofloxacin and colistin) in 2011 compared with
2001 (13.5% vs. 42.1%; P = 0.023), whereas the resistance to colistin increased
significantly (11.1% vs. 62.2%; P < 0.001). Burkholderia cepacia complex and
nontuberculous mycobacteria were not detected in 2001 but in 2011 in 7.4% (n = 9)
and 7.4% (n = 9) of patients, respectively. B. cepacia complex isolates belonged
to 8 multilocus sequence types. CONCLUSIONS: Our retrospective analysis revealed
an increase of important CF-related pathogens, the emergence of new pathogens and
a substantial increase of multidrug-resistant CF-specific isolates. Our findings
are of importance to clinicians for the alertness of local epidemiology, which
may be useful for prevention and treatment strategies.
PMID- 25851070
TI - Antiretroviral Therapy Use During Pregnancy and the Risk of Small for Gestational
Age Birth in a Medicaid Population.
AB - BACKGROUND: Several studies have assessed the association between antiretroviral
(ARV) therapy use during pregnancy and small for gestational age (SGA), but the
evidence remains incompletely elucidated. METHODS: We linked data from Tennessee
Medicaid files and vital records to evaluate pregnancies among human
immunodeficiency virus (HIV)-infected women who delivered between 1994 and 2009.
Maternal HIV status was defined based on diagnosis codes, ARV prescriptions and
laboratory codes for CD4 count or HIV RNA assays. ARV use was identified from
pharmacy claims. Risk of SGA (defined as birth weight below the 10th percentile
for gestational age) and preterm birth was evaluated using logistic regression
models. RESULTS: Four hundred and seventy-seven HIV-infected pregnant women
contributing 604 singleton pregnancies were identified; 156 (26%) delivered SGA
infants. ARV use during pregnancy was not associated with SGA [adjusted odds
ratio: 0.93; 95% confidence interval (CI): 0.56-1.56] or preterm birth (adjusted
odds ratio: 0.74; 95% CI: 0.42-1.32). Exposure to a protease inhibitor during the
first trimester was associated with a lower risk of SGA (odds ratio: 0.54; 95%
CI: 0.29-1.01) compared with non-exposure to a protease inhibitor throughout
pregnancy. CONCLUSIONS: We observed no evidence of an association between ARV
exposure during pregnancy and SGA delivery in this Medicaid cohort of HIV
infected women.
PMID- 25851071
TI - False-positive (1,3) beta-D-glucan assay in a patient with intracranial
germinoma.
PMID- 25851072
TI - Use of paracetamol during pregnancy and child neurological development.
AB - Paracetamol (acetaminophen) remains the first line for the treatment of pain and
fever in pregnancy. Recently published epidemiological studies suggested a
possible association between paracetamol exposure in utero and attention-deficit
hyperactivity disorder/hyperkinetic disorder (ADHD/HKD) or adverse development
issues in children. However, the effects observed are in the weak to moderate
range, and limitations in the studies' design prevent inference on a causal
association with ADHD/HKD or child neurological development. In parallel, recent
animal data showed that cognition and behaviour may be altered following exposure
to therapeutic doses of paracetamol during early development. These effects may
be mediated by interference of paracetamol with brain-derived neurotrophic
factor, neurotransmitter systems (including serotonergic, dopaminergic,
adrenergic, as well as the endogenous endocannabinoid systems), or cyclooxygenase
2. However, no firm conclusion can be made on the relevance of these observations
to humans. We conclude that additional well-designed cohort studies are necessary
to confirm or disprove the association. In the context of current knowledge,
paracetamol is still to be considered safe in pregnancy and should remain the
first-line treatment for pain and fever.
PMID- 25851073
TI - Implementation of the National Nursing Quality Report Initiative in Canada:
Insights From Pilot Participants.
AB - A qualitative study was undertaken to explore the perceptions and experiences of
nurse leaders associated with their participation in the pilot testing of a
national nursing database. Interviews with 18 participants were conducted and
analyzed using a direct content analysis approach. Three themes emerged including
selecting, accessing, and uploading indicators; using indicators and monitoring
tools for improvement; and perceiving involvement as a catalyst. Study findings
may inform quality improvement efforts in health care organizations.
PMID- 25851074
TI - Tests of Eustachian tube function: a review.
AB - BACKGROUND: Eustachian tube (ET) dysfunction is a common but poorly understood
cause of patient symptoms, and an important aetiological factor in the
development of middle ear pathology. Despite this, there are no specific tests of
ET function in widespread clinical use and no identified 'gold standard' with
which to diagnose the disease. OBJECTIVE: This review aims to review the
literature to identify currently available tests of ET function and, where
possible, report on their accuracy. TYPE OF REVIEW: Narrative systematic review.
SEARCH STRATEGY: MEDLINE, EMBASE, Biosis and the Cochrane library were searched
and reference lists reviewed for relevant articles. EVALUATION METHOD: Tests in
included studies were required to measure a physiological function of the ET, or
play a role in the diagnosis of poor ET function. Significant variation in
demographic characteristics, disease presentation and severity, and technological
approaches only permitted narrative systematic review. RESULTS: While many tests
of ET function have been developed, with some in routine clinical use, all have
significant limitations. Published accuracy data are limited and of differing
quality due to the variability incomparative tests, and the spectrum of
otological disorders associated with ET dysfunction. CONCLUSIONS: Currently, no
single test could be considered a 'gold standard' for the diagnosis of ET
dysfunction, but there is some evidence that diagnostic accuracy can be improved
by combining the results of different objective tests and patient-reported
outcome measures. Further development of ET function tests is required to
facilitate the accurate diagnosis of patients and allow outcome reporting for new
interventions.
PMID- 25851075
TI - Amplitude Modulation Detection and Speech Recognition in Late-Implanted
Prelingually and Postlingually Deafened Cochlear Implant Users.
AB - OBJECTIVES: Many late-implanted prelingually deafened cochlear implant (CI)
patients struggle to obtain open-set speech understanding. Because it is known
that low-frequency temporal-envelope information contains important cues for
speech understanding, the goal of this study was to compare the temporal-envelope
processing abilities of late-implanted prelingually and postlingually deafened CI
users. Furthermore, the possible relation between temporal processing abilities
and speech recognition performances was investigated. DESIGN: Amplitude
modulation detection thresholds were obtained in eight prelingually and 18
postlingually deafened CI users, by means of a sinusoidally modulated broadband
noise carrier, presented through a loudspeaker to the CI user's clinical device.
Thresholds were determined with a two-down-one-up three-interval oddity adaptive
procedure, at seven modulation frequencies. Phoneme recognition (consonant
nucleus-consonant [CNC]) scores (percentage correct at 65 dB SPL) were gathered
for all CI users. For the prelingually deafened group, scores on two additional
speech tests were obtained: (1) a closed-set monosyllable-trochee-spondee test
(percentage correct scores at 65 dB SPL on word recognition and categorization of
the suprasegmental word patterns), and (2) a speech tracking test (number of
correctly repeated words per minute) with texts specifically designed for this
population. RESULTS: The prelingually deafened CI users had a significantly lower
sensitivity to amplitude modulations than the postlingually deafened CI users,
and the attenuation rate of their temporal modulation transfer function (TMTF)
was greater. None of the prelingually deafened CI users were able to detect
modulations at 150 and 200 Hz. High and significant correlations were found
between the results on the amplitude modulation detection test and CNC phoneme
scores, for the entire group of CI users. In the prelingually deafened group, CNC
phoneme scores, word scores on the monosyllable-trochee-spondee test, and speech
tracking scores correlated significantly with the mean amplitude modulation
detection threshold of the modulation frequencies between 5 and 100 Hz and with
almost all separate amplitude modulation thresholds. High correlations with these
speech measures were also found for the attenuation rate of and the surface area
below the TMTF. In postlingually deafened CI users, CNC phoneme scores only
correlated significantly with the 100-Hz and 150-Hz amplitude modulation
thresholds, as well as with the attenuation rate of and surface area below the
TMTF. CONCLUSIONS: Prelingually deafened CI users were less sensitive to temporal
modulations than postlingually deafened CI users, and the attenuation rate of
their TMTF was steeper. For all CI users, subjects with better amplitude
modulation detection skills tended to score better on measures of speech
understanding. Significant correlations with low modulation frequencies were
found only for the prelingually deafened CI users and not for the postlingually
deafened CI users.
PMID- 25851076
TI - Decisional support to prevent adverse drug reactions of long latency: pilot
randomized controlled intervention for glucocorticoid-induced diabetes.
AB - RATIONALE, AIMS, AND OBJECTIVES: Long-term exposure to glucocorticoids can cause
adverse drug reactions of long latency (ADRLLs), including glucocorticoid-induced
diabetes mellitus (GID). Providers can monitor for GID using the glycosylated
haemoglobin blood (HbA1C) test. This study examined the utility of decisional
support to improve HbA1C-based screening for GID. US veterans were identified as
chronic users of oral glucocorticoids (>120 days of oral glucocorticoids in the
last 2 years). The primary care providers caring for these patients were the
target of the intervention. Providers were randomized to receive automatic HbA1C
orders for their patients receiving chronic glucocorticoid or usual care.
METHODS: This study was a pilot two-arm, group-randomized, controlled trial (n =
12 providers, n = 38 patients). Data collection occurred from 5 May 2013 until 10
January 2014. A pharmacist generated the order for an HbA1C through the
electronic medical record. The time between the intervention start date and the
date on which an HbA1C order was signed were compared using Cox proportional and
hierarchical linear regression. RESULTS: The time to sign HbA1C orders (mean 12.0
days for the intervention arm; 104.0 days for control arm) was associated with
significant differences favouring the intervention [HR (Hazard Ratio) 50.2, P <
0.001, confidence interval (CI) 6.3 to 398.7]. For the intervention group, 95% of
orders were signed, whereas only 12% of control providers signed orders (odds
ratio 150, P < 0.001, CI 12.4 to 1812.9). CONCLUSIONS: The results of this study
strongly suggest that the clinical pharmacist-triggered order intervention is
effective. This method of computerized decisional support may be useful in
improving screening for GID and ADRLLs.
PMID- 25851077
TI - Differences in performance and transcriptome-wide gene expression associated with
Rhagoletis (Diptera: Tephritidae) larvae feeding in alternate host fruit
environments.
AB - Host race formation, the establishment of new populations using novel resources,
is a major hypothesized mechanism of ecological speciation, especially in plant
feeding insects. The initial stages of host race formation will often involve
phenotypic plasticity on the novel resource, with subsequent genetically based
adaptations enhancing host-associated fitness differences. Several studies have
explored the physiology of the plastic responses of insects to novel host
environments. However, the mechanisms underlying evolved differences among host
races and species remain poorly understood. Here, we demonstrate a reciprocal
larval performance difference between two closely related species of Rhagoletis
flies, R. pomonella and R. zephyria, specialized for feeding in apple and
snowberry fruit, respectively. Microarray analysis of fly larvae feeding in
apples versus snowberries revealed patterns of transcriptome-wide differential
gene expression consistent with both plastic and evolved responses to the
different fruit resources, most notably for detoxification-related genes such as
cytochrome p450s. Transcripts exhibiting evolved expression differences between
species tended to also demonstrate plastic responses to fruit environment. The
observed pattern suggests that Rhagoletis larvae exhibit extensive plasticity in
gene expression in response to novel fruit that may potentiate shifts to new
hosts. Subsequent selection, particularly selection to suppress initially costly
plastic responses, could account for the evolved expression differences observed
between R. pomonella and R. zephyria, creating specialized races and new fly
species. Thus, genetically based ecological adaptations generating new
biodiversity may often evolve from initial plastic responses in gene expression
to the challenges posed by novel environments.
PMID- 25851078
TI - The influence of prenatal intimate partner violence exposure on hypothalamic
pituitary-adrenal axis reactivity and childhood internalizing and externalizing
symptoms.
AB - This prospective longitudinal study examines the long-term influence of intimate
partner violence (IPV) exposure in utero. We hypothesized that (a) prenatal IPV
increases risk for internalizing and externalizing problems as well as for a
profile of dysregulated cortisol reactivity, and (b) patterns of cortisol hyper-
and hyporeactivity are differentially associated with internalizing and
externalizing problems. The participants were 119 10-year-old children. Their
mothers reported their IPV experiences and distress during pregnancy. Child and
maternal reports of internalizing and externalizing problems as well as lifetime
IPV exposure were obtained. Salivary cortisol was assessed at baseline, 20 min,
and 40 min after challenge. The results partially supported our hypotheses:
Exposure to IPV during pregnancy predicted child-reported internalizing and
externalizing problems, mother ratings of child externalizing problems, and a
profile of high cortisol secretion before and after stress challenge. The results
were significant above and beyond the influence of maternal distress during
pregnancy and IPV that occurred during the child's life. In addition, a profile
of high cortisol secretion was associated with maternal reports of child
internalizing behaviors. Findings support the growing consensus that prenatal
stress can lead to lasting disruptions in adaptation and highlight the need for
more longitudinal examinations of prenatal IPV exposure.
PMID- 25851079
TI - The influence of electromyographic recording methods and the innervation zone on
the mean power frequency-torque relationships.
AB - This study examined the effects of electromyographic (EMG) recording methods and
innervation zone (IZ) on the mean power frequency (MPF)-torque relationships.
Nine subjects performed isometric ramp muscle actions of the leg extensors from
5% to 100% of maximal voluntary contraction with an eight channel linear
electrode array over the IZ of the vastus lateralis. The slopes were calculated
from the log-transformed monopolar and bipolar EMG MPF-torque relationships for
each channel and subject and 95% confidence intervals (CI) were constructed
around the slopes for each relationship and the composite of the slopes. Twenty
two to 55% of the subjects exhibited 95% CIs that did not include a slope of zero
for the monopolar EMG MPF-torque relationships while 25-75% of the subjects
exhibited 95% CIs that did not include a slope of zero for the bipolar EMG MPF
torque relationships. The composite of the slopes from the EMG MPF-torque
relationships were not significantly different from zero for any method or
channel, however, the method and IZ location slightly influenced the number of
significant slopes on a subject-by-subject basis. The log-transform model
indicated that EMG MPF-torque patterns were nonlinear regardless of recording
method or distance from the IZ.
PMID- 25851080
TI - Changes in hippocampal synaptic functions and protein expression in monosodium
glutamate-treated obese mice during development of glucose intolerance.
AB - Glucose is the sole neural fuel for the brain and is essential for cognitive
function. Abnormalities in glucose tolerance may be associated with impairments
in cognitive function. Experimental obese model mice can be generated by an
intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5
days from 1 day after birth. MSG-treated mice have been shown to develop glucose
intolerance and exhibit chronic neuroendocrine dysfunction associated with marked
cognitive malfunctions at 28-29 weeks old. Although hippocampal synaptic
plasticity is impaired in MSG-treated mice, changes in synaptic transmission
remain unknown. Here, we investigated whether glucose intolerance influenced
cognitive function, synaptic properties and protein expression in the
hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance
due to an impairment in the effectiveness of insulin actions, and showed
cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP)
at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired,
and the relationship between the slope of extracellular field excitatory
postsynaptic potential and stimulus intensity of synaptic transmission was weaker
in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and
GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated
mice. These results suggest that deficits in glutamatergic presynapses as well as
postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the
development of glucose intolerance, though it remains unknown whether impaired
LTP is due to altered inhibitory transmission. It may be important to examine
changes in glucose tolerance in order to prevent cognitive malfunctions
associated with diabetes.
PMID- 25851081
TI - Evaluation of patello-femoral alignment by CT scans: interobserver reliability of
several parameters.
AB - Patello-femoral malalignment (PFM) is a common cause of disability often related
to patello-femoral syndrome (PFS). Several causes have been taken into account; a
proper diagnosis requires instrumental imaging and a methodical evaluation of
different parameters. The aim of the present study was to identify the most
reliable parameters for measuring patello-femoral and inferior limb alignment by
CT. Twenty randomly selected patients suffering from PFS for a total of 40 knees
were studied by static CT scans in order to assess patellar tilt, patellar
displacement, patellar and trochlear morphology and inferior limb alignment. All
known parameters were measured; the variability of the measurements between
observers was evaluated by boxplots, Pearson's correlation coefficients, and
infraclass correlation coefficient [ICC(2,1)] based on a two-way random effect
model. Bland-Altman mean differences and 95 % limits of agreement were computed
for each pair of measurements. Patellar tilt parameters appeared equally
reliable; patellar displacement is best measured with BoTot that showed an ICC of
0.889; morphology is best measured with WibergTot, with an ICC of 0.862; lastly,
for the inferior limb alignment parameters' analysis, FTV outperformed the others
in terms of reliability. The present study allowed us to select a limited number
of reliable parameters in the evaluation of patello-femoral and inferior limb
alignment. The use of these parameters may also result in a more reliable
comparison of studies on PFM and in a better evaluation of the treatment
outcomes.
PMID- 25851082
TI - Semantic network mapping of religious material: testing multi-agent computer
models of social theories against real-world data.
AB - Agent-based modeling allows researchers to investigate theories of complex social
phenomena and subsequently use the model to generate new hypotheses that can then
be compared to real-world data. However, computer modeling has been underutilized
in regard to the understanding of religious systems, which often require very
complex theories with multiple interacting variables (Braxton et al. in Method
Theory Study Relig 24(3):267-290, 2012. doi: 10.1163/157006812X635709 ; Lane in J
Cogn Sci Relig 1(2):161-180, 2013). This paper presents an example of how
computer modeling can be used to explore, test, and further understand religious
systems, specifically looking at one prominent theory of religious ritual. The
process is continuous: theory building, hypothesis generation, testing against
real-world data, and improving the model. In this example, the output of an agent
based model of religious behavior is compared against real-world religious
sermons and texts using semantic network analysis. It finds that most religious
materials exhibit unique scale-free small-world properties and that a concept's
centrality in a religious schema best predicts its frequency of presentation.
These results reveal that there adjustments need to be made to existing models of
religious ritual systems and provide parameters for future models. The paper ends
with a discussion of implications for a new multi-agent model of doctrinal ritual
behaviors as well as propositions for further interdisciplinary research
concerning the multi-agent modeling of religious ritual behaviors.
PMID- 25851084
TI - Cardiovascular Pathology: From whence we came ... to where we are going.
PMID- 25851083
TI - Autologous, Noncultured Epidermal Cell Suspension Grafting in the Management of
Mechanically and Chemically Induced Leukodermic Scars.
AB - BACKGROUND: Melanocyte-keratinocyte transplant procedure (MKTP) successfully
repigments postburn leukodermic scars. OBJECTIVE: To further investigate the
efficacy and limitations of MKTP for treatment of mechanically and chemically
induced leukodermic scars. METHODS: Ten patients with mechanically or chemically
induced, depigmented or hypopigmented scars were preoperatively evaluated with
Wood's light examination, treated with MKTP, and followed for at least 6 months,
with monitoring of repigmentation and colour matching. RESULTS: Nine patients
attended at least 6 months of follow-up. Six patients showed no fluorescence of
scars under Wood's lamp. All patients whose lesions didn't fluoresce displayed
less than 50% repigmentation, with 5 of 6 attaining 0% to 24%. Of the 3 patients
displaying bright or some fluorescence, more than 95% repigmentation was achieved
in 2 patients (skin phototypes V and VI), while less than 24% was attained for
the third (skin phototype II). CONCLUSIONS: In this small case series, lack of
fluorescence in leukodermic scars may be a useful negative prognostic indicator
for MKTP, but additional trials are needed to verify that this is not due to
melanocompetency.
PMID- 25851086
TI - Introduction.
PMID- 25851085
TI - Plexogenic pulmonary hypertension associated with intravenous cocaine abuse.
AB - Intravenous drug abuse related plexogenic pulmonary hypertension unassociated
with recurrent thromboembolism or foreign-body granulomatous disease of the lung
has not been previously reported. Herein, we describe the occurrence of fatal
plexogenic pulmonary hypertension in a 33-year-old Hispanic woman who had a
history of chronic intravenous drug abuse. In the absence of other known causes,
cocaine-induced chronic vasoconstriction was the most probable pathogenic
mechanism of plexogenic pulmonary hypertension in this patient.
PMID- 25851087
TI - Approach to the analysis of cardiac valve prostheses as surgical pathology or
autopsy specimens.
AB - Pathologists are likely to encounter substitute heart valves with increasing
frequency. Informed evaluation of such valves provides valuable information that
contributes to both patient care and our understanding of the pathobiology of
host interactions with mechanical devices. This article summarizes the most
important considerations underlying such analyses-including valve identification,
common morphologic features and modes of failure, technical details of
evaluation, and potential pitfalls.
PMID- 25851088
TI - Myxomatous mitral valve disease and related entities: The role of matrix in
valvular heart disease.
AB - Myxomatous mitral valve disease is a cause of prolapse of mitral valve leaflet(s)
into the left atrium. In this condition there is a loss of collagen from the
leaflet and an accumulation of glycosaminoglycan. Complications of myxomatous
mitral valve disease include infective endocarditis, mitral regurgitation, sudden
death, and stroke. Mitral valve prolapse has been reported to occur in
association with many syndromes. In some of these, such as Marfan syndrome, the
pathology of the mitral valve has been well described and is that of a myxomatous
valve. However, in some of the other disorders associated with mitral valve
prolapse, there is no information yet available on the valve pathology, and this
would be useful in order to better understand the pathogenesis of myxomatous
mitral valve disease.
PMID- 25851089
TI - Update on pathogenesis of infective endocarditis.
AB - Specific interactions between pathogens and host factors contribute to the
apparent tissue and microbial selectivity in infective endocarditis. Streptococci
and staphylococci can produce exopolysaccharides and peptides that have been
implicated in adherence to host factors. The presence of a platelet-fibrin matrix
on the surface of endothelium can serve as a nidus for colonization by gram
positive cocci, which in turn can promote further aggregation of platelets.
Tissue factor expression by valvular endothelial cells is low but can be turned
on by endocytosis of staphylococci-this could favor infected thrombus formation.
The presence of a foreign body such as a prosthetic heart valve increases the
risk of endocarditis. Platelets can promote adherence of staphylococci to foreign
body surfaces. Infection of heart valves is the result of influences that in the
end will favor microbial attachment and survival. Normal endothelium is resistant
to colonization by microorganisms. Antibodies and phagocytes offer some
protection against the development of endocarditis. Platelets produce
microbicidal proteins that appear important in containing the infection. New
diagnostic criteria for endocarditis take into account the pathogenetic
characteristics of the disease.
PMID- 25851090
TI - Complications of cardiac valve surgery and their autopsy investigation.
AB - This review describes the broad spectrum of complications that may attend cardiac
valve replacement surgery. Patient morbidity and mortality may be a consequence
of preoperative condition or care, operative complications, or postoperative
course. Careful autopsy examination of patient deaths, correlated with clinical
information, will usually reveal an explanation for a patient's demise, as well
as precipitating or contributing factors. The autopsy is particularly valuable if
it can demonstrate technical, prosthetic, or other unexpected findings whose
communication to clinicians and manufacturers can serve to improve the care of
subsequent patients, or the development of improved prostheses.
PMID- 25851091
TI - New concepts in the design and use of biological prosthetic valves.
AB - The natural aortic valve is a structure that has thus far eluded all attempts at
duplication with synthetic materials. Real success in the replacement of the
aortic valve has come about primarily through the use of biological devices, such
as the porcine aortic valve xenograft. In the future, bioprostheses based more
closely on the natural aortic valve may ultimately succeed where synthetic
approaches have failed. Some recent advances in the design and development of
bioprosthetic heart valves, such as the absence of a stent and the better
preservation of the valve's natural biomechanical properties, show considerable
promise in improving the long term durability of these devices. With a greater
understanding of the structure/function relationship of the aortic valve at the
micromechanical level, the future of bioprostheses may be even more biologically
oriented than it is today.
PMID- 25851092
TI - Ebstein's malformation.
PMID- 25851093
TI - Ebstein's malformation.
PMID- 25851094
TI - Images in Anesthesiology: Spontaneous Hyphema after Cardiac Surgery.
PMID- 25851095
TI - Is there a place for nutrition-sensitive agriculture?
AB - The focus of the review paper is to discuss how biotechnological innovations are
opening new frontiers to mitigate nutrition in key agricultural crops with
potential for large-scale health impact to people in Africa. The general
objective of the Africa Biofortified Sorghum (ABS) project is to develop and
deploy sorghum with enhanced pro-vitamin A to farmers and end-users in Africa to
alleviate vitamin A-related micronutrient deficiency diseases. To achieve this
objective the project technology development team has developed several promising
high pro-vitamin A sorghum events. ABS 203 events are so far the most advanced
and well-characterised lead events with about 12 MUg beta-carotene/g tissue which
would supply about 40-50 % of the daily recommended vitamin A at harvest. Through
gene expression optimisation other events with higher amounts of pro-vitamin A,
including ABS 214, ABS 235, ABS 239 with 25, 30-40, 40-50 MUg beta-carotene/g
tissue, respectively, have been developed. ABS 239 would provide twice
recommended pro-vitamin A at harvest, 50-90 % after 3 months storage and 13-45 %
after 6 months storage for children. Preliminary results of introgression of ABS
pro-vitamin A traits into local sorghum varieties in target countries Nigeria and
Kenya show stable introgression of ABS vitamin A into local farmer-preferred
sorghums varieties. ABS gene Intellectual Property Rights and Freedom to Operate
have been donated for use royalty free for Africa. Prior to the focus on the
current target countries, the project was implemented by fourteen institutions in
Africa and the USA. For the next 5 years, the project will complete ABS product
development, complete regulatory science data package and apply for product
deregulation in target African countries.
PMID- 25851096
TI - Rio1 promotes rDNA stability and downregulates RNA polymerase I to ensure rDNA
segregation.
AB - The conserved protein kinase Rio1 localizes to the cytoplasm and nucleus of
eukaryotic cells. While the roles of Rio1 in the cytoplasm are well
characterized, its nuclear function remains unknown. Here we show that nuclear
Rio1 promotes rDNA array stability and segregation in Saccharomyces cerevisiae.
During rDNA replication in S phase, Rio1 downregulates RNA polymerase I (PolI)
and recruits the histone deacetylase Sir2. Both interventions ensure rDNA copy
number homeostasis and prevent the formation of extrachromosomal rDNA circles,
which are linked to accelerated ageing in yeast. During anaphase, Rio1
downregulates PolI by targeting its subunit Rpa43, causing PolI to dissociate
from the rDNA. By stimulating the processing of PolI-generated transcripts at the
rDNA, Rio1 allows for rDNA condensation and segregation in late anaphase. These
events finalize the genome transmission process. We identify Rio1 as an essential
nucleolar housekeeper that integrates rDNA replication and segregation with
ribosome biogenesis.
PMID- 25851097
TI - A pyrosequencing insight into sprawling bacterial diversity and community
dynamics in decaying deadwood logs of Fagus sylvatica and Picea abies.
AB - Deadwood is an important biodiversity hotspot in forest ecosystems. While
saproxylic insects and wood-inhabiting fungi have been studied extensively,
little is known about deadwood-inhabiting bacteria. The study we present is among
the first to compare bacterial diversity and community structure of deadwood
under field conditions. We therefore compared deadwood logs of two temperate
forest tree species Fagus sylvatica and Picea abies using 16S rDNA pyrosequencing
to identify changes in bacterial diversity and community structure at different
stages of decay in forest plots under different management regimes.
Alphaproteobacteria, Acidobacteria and Actinobacteria were the dominant taxonomic
groups in both tree species. There were no differences in bacterial OTU richness
between deadwood of Fagus sylvatica and Picea abies. Bacteria from the order
Rhizobiales became more abundant during the intermediate and advanced stages of
decay, accounting for up to 25% of the entire bacterial community in such logs.
The most dominant OTU was taxonomically assigned to the genus Methylovirgula,
which was recently described in a woodblock experiment of Fagus sylvatica.
Besides tree species we were able to demonstrate that deadwood physico-chemical
properties, in particular remaining mass, relative wood moisture, pH, and C/N
ratio serve as drivers of community composition of deadwood-inhabiting bacteria.
PMID- 25851099
TI - Safinamide: first global approval.
AB - Safinamide (Xadago((r))) is an oral alpha-aminoamide derivative developed by
Newron for the treatment of Parkinson's disease (PD). The drug has both
dopaminergic properties (highly selective and reversible inhibition of monoamine
oxidase-B) and non-dopaminergic properties (selective sodium channel blockade and
calcium channel modulation, with consequent inhibition of excessive glutamate
release). Safinamide is approved in the EU, Iceland, Lichtenstein and Norway, as
an add-on therapy to stable-dose levodopa, alone or in combination with other PD
therapies in mid- to late-stage fluctuating PD patients; regulatory submissions
have also been filed in the USA and Switzerland for its use in this indication.
Additional submissions have been made in the USA, Iceland, Lichtenstein, Norway
and Switzerland for early-stage PD. Safinamide has also undergone phase II
investigation in PD patients with drug-induced dyskinesia (France, Germany,
Austria, Canada and South Africa) or cognitive impairment (USA and Spain). This
article summarizes the milestones in the development of safinamide leading to its
first approval for PD.
PMID- 25851098
TI - Depression in type 2 diabetes mellitus: prevalence, impact, and treatment.
AB - Clinically significant depression is present in one of every four people with
type 2 diabetes mellitus (T2DM). Depression increases the risk of the development
of T2DM and the subsequent risks of hyperglycemia, insulin resistance, and micro-
and macrovascular complications. Conversely, a diagnosis of T2DM increases the
risk of incident depression and can contribute to a more severe course of
depression. This linkage reflects a shared etiology consisting of complex
bidirectional interactions among multiple variables, a process that may include
autonomic and neurohormonal dysregulation, weight gain, inflammation, and
hippocampal structural alterations. Two recent meta-analyses of randomized
controlled depression treatment trials in patients with T2DM concluded that
psychotherapy and antidepressant medication (ADM) were each moderately effective
for depression and that cognitive behavior therapy (CBT) had beneficial effects
on glycemic control. However, the number of studies (and patients exposed to
randomized treatment) included in these analyses is extremely small and limits
the certainty of conclusions that can be drawn from the data. Ultimately, there
is no escaping the paucity of the evidence base and the need for additional
controlled trials that specifically address depression management in T2DM. Future
trials should determine both the effects of treatment and the change in
depression during treatment on measures of mood, glycemic control, and medical
outcome.
PMID- 25851100
TI - Foreword: all things considered about probiotics, prebiotics and intestinal
microbiota in children - from bench to bedside.
AB - There are numerorus published and ongoing experimental/clinical studies about
probiotics and prebiotics, intestinal microbiota and nutrition. Three years ago,
at the first International Symposium of Probiotics Prebiotics in Paediatrics in
Istanbul (2012) we highlighted the 'paediatric perspective' on these issues and
brought together more than 40 global key opinion leaders and 400 attendants to
have a chance to extensively discuss the past, present and the future. In 2014,
the second state of art congress, held in Antalya, aimed to discuss the gut
microbiota and microbiotics and their impact through lifespan. Selected papers of
this conference are presented in this special issue 'prebiotics and probiotics in
paediatrics' of Beneficial Microbes. A summary of the conference results is
provided below.
PMID- 25851101
TI - Bugs for atopy: the Lactobacillus rhamnosus GG strategy for food allergy
prevention and treatment in children.
AB - Food allergy (FA) is a major health issue for children living in Western
countries. At this time the only proven treatment for FA is elimination of
offender antigen from the diet. It is becoming clear that the development of gut
microbiota exerts a profound influence on immune system maturation and tolerance
acquisition. Increasing evidence suggests that perturbations in gut microbiota
composition of infants are implicated in the pathogenesis of FA. These findings
have unveiled new strategies to prevent and treat FA using probiotics bacteria or
bacterial substance to limit T-helper (Th)/Th2 bias, which changes during the
disease course. Selected probiotics administered during infancy may have a role
in the prevention and treatment of FA. Lactobacillus rhamnosus GG (LGG) is the
most studied probiotic in this field. Administration of LGG in early life have a
role in FA prevention. Preliminary evidence shows that LGG accelerates oral
tolerance acquisition in cow's milk allergic infants. We are understanding the
mechanisms elicited by LGG and metabolites in influencing food allergen
sensitization. A deeper definition of these mechanisms is opening the way to new
immunotherapeutics for children affected by FA that can efficiently limit the
disease burden.
PMID- 25851104
TI - Addition of ethylene to a pi-conjugated two-dimensional nickel-based
organometallic framework with implications for olefin separation.
AB - We have investigated the mechanism for the reversible addition of ethylene to a
periodic 2D network of square-planar nickel centers ([Ni(SC)4]n) using density
functional theory. The mechanism is analogous to that for homogeneous olefin
binding to metal bis(dithiolene) complexes. We considered periodic boundary
calculations (PBC) as well as clusters containing up to 12 nickel atoms using a
screened hybrid density functional to obtain accurate reaction barriers. Several
different products were analyzed. The lowest-energy route begins with the
addition of ethylene across the nickel-sulfur bond, which has previously not been
considered for this system. The effect of the addition of several alkene
molecules simultaneously on the surface was investigated to determine the
potential efficiency of this material. This material is a candidate for alkene
purification as it exhibits similar reactivity to its molecular analog in terms
of the relative stability of products, energy barriers, and molecular efficiency
while also providing the intrinsic technical benefits of heterogeneous catalysis.
PMID- 25851102
TI - The impact of lifestyle intervention on sedentary time in individuals at high
risk of diabetes.
AB - AIMS/HYPOTHESIS: The Diabetes Prevention Program (DPP) lifestyle intervention
successfully achieved its goal of increasing leisure physical activity levels.
This current study examines whether the lifestyle intervention also changed time
spent being sedentary and the impact of sedentary time on diabetes development in
this cohort. METHODS: 3,232 DPP participants provided baseline data. Sedentary
behaviour was assessed via an interviewer-administered questionnaire and reported
as time spent watching television specifically (or combined with sitting at
work). Mean change in sedentary time was examined using repeated measures ANCOVA.
The relationship between sedentary time and diabetes incidence was determined
using Cox proportional hazards models. RESULTS: During the DPP follow-up (mean:
3.2 years), sedentary time declined more in the lifestyle than the metformin or
placebo participants (p < 0.05). For the lifestyle group, the decrease in
reported mean television watching time (22 [95% CI 26, 17] min/day) was greater
than in the metformin or placebo groups (p < 0.001). Combining all participants
together, there was a significantly increased risk of developing diabetes with
increased television watching (3.4% per hour spent watching television), after
controlling for age, sex, treatment arm and leisure physical activity (p < 0.01),
which was attenuated when time-dependent weight was added to the model.
CONCLUSIONS/INTERPRETATION: In the DPP, the lifestyle intervention was effective
at reducing sedentary time, which was not a primary goal. In addition, in all
treatment arms, individuals with lower levels of sedentary time had a lower risk
of developing diabetes. Future lifestyle intervention programmes should emphasise
reducing television watching and other sedentary behaviours in addition to
increasing physical activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00004992.
PMID- 25851103
TI - Clinical management and humoral immune responses to rabies post-exposure
prophylaxis among three patients who received solid organs from a donor with
rabies.
AB - BACKGROUND: The rabies virus causes a fatal encephalitis and can be transmitted
through organ transplantation. In 2013, a man developed rabies 18 months after
receiving a kidney from a donor with rabies, who was not known to have been
infected when the organs were procured. Three additional persons who received
organs from the same donor (liver, kidney, heart), all of whom were not
vaccinated for rabies before transplantation, received rabies post-exposure
prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as
soon as the diagnosis of rabies was made in the donor (18 months after their
transplant surgeries). We describe their clinical management. METHODS: As the 3
recipients were all on immunosuppressive medications, post-vaccination serologic
testing was performed using the rapid fluorescent focus inhibition test to
measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody
response to administration of rabies vaccine was defined as detection of RVNAs at
a concentration >=0.1 IU/mL from a serum specimen collected >=7 days after the
fifth vaccine dose. RESULTS: All 3 recipients demonstrated an acceptable antibody
response despite their immunosuppressed states. More than 36 months have passed
since their transplant surgeries, and all 3 recipients have no evidence of
rabies. CONCLUSIONS: The survival of 3 previously unvaccinated recipients of
solid organs from a donor with rabies is unexpected. Although the precise factors
that led to their survival remain unclear, our data suggest that PEP can possibly
enhance transplant safety in settings in which donors are retrospectively
diagnosed with rabies.
PMID- 25851105
TI - On the interactions of leflunomide and teriflunomide within receptor cavity--NMR
studies and energy calculations.
AB - Leflunomide is a disease-modifying antirheumatic drug with antiinflammatory and
immunosuppressive activity used for the treatment of psoriatic and rheumatoid
arthritis. It undergoes rapid metabolization to teriflunomide, a metabolite that
is responsible for the biological activity of leflunomide. Continuing our
investigations on the interactions of biologically important azahetarenes with
the environment, we focused on leflunomide and its active metabolite,
teriflunomide, considering the interactions teriflunomide-amino acid within the
target protein (dihydroorotate dehydrogenase) using density functional theory, as
well as ONIOM techniques. The results of theoretical studies have shown that the
interactions of teriflunomide with tyrosine and arginine involve principally the
amide fragment of teriflunomide. The presence of the internal hydrogen bond
between (Z)-teriflunomide carbonyl oxygen and enolic hydroxyl decreases the
interaction strength between teriflunomide and tyrosine or arginine. Even the E
isomer of teriflunomide would usually provide a stronger interaction
teriflunomide-amino acid than the Z isomer with the internal hydrogen bond.
PMID- 25851106
TI - Theoretical study of spectroscopic constants and anharmonic force field of SiF2.
AB - The equilibrium structure, spectroscopy constants, and anharmonic force field of
SiF2 have been investigated at MP2, B3LYP, and B3PW91 levels of theory employing
two basis sets cc-pVQZ and cc-pVTZ, respectively. The obtained equilibrium
geometries, rotational constants, fundamental vibrational wave numbers, and
centrifugal distortion constants are compared with the available experimental
data or the previous theoretical values. The MP2/cc-pVQZ results of SiF2 are in
excellent agreement with the available experimental data and afford a marked
improvement over B3LYP/cc-pVQZ and B3PW91/cc-pVQZ in the calculation of
spectroscopic constants and force constants of SiF2. The basis set enhancement
beyond cc-pVQZ does not lead to a major improvement so that the cc-pVQZ basis set
is sufficient for SiF2. The MP2/cc-pVQZ results may provide useful data for the
spectroscopic experiment studies of SiF2. The used DFT method is also an
advisable choice to study anharmonic force field of SiF2.
PMID- 25851107
TI - Understanding the role of the trifluoromethyl group in reactivity and
regioselectivity in [3+2] cycloaddition reactions of enol acetates with nitrones.
A DFT study.
AB - The mechanism of the [3+2] cycloaddition (32CA) reaction of C-phenyl-N
methylnitrone with ethyl trifluoroacetoacetate has been theoretically studied at
the MPWB1K/6-311G(d,p) level. This 32CA reaction, in which the enol form of the
beta-keto ester participates as the ethylene component, takes place with complete
ortho regioselectivity and exo stereoselectivity. The presence of the CF3 group
in the beta-position in the enol acetate accelerates the 32CA reaction, but it
does not modify the regioselectivity, which is controlled by the presence of the
ester group. While ortho regioselectivity is reproduced by the MPWB1K
calculations, the endo selectivity is not. The inclusion of solvent effects
slightly decreases the reactivity but does not modify the gas phase
selectivities. Analysis of the DFT global reactivity indices and the Parr
functions in reagents provide a rationalization for the participation of ethyl
trifluoroacetoacetate and the regioselectivity in this zw-type 32CA reaction.
PMID- 25851108
TI - A theoretical study of the unfolding pathway of reduced human serum albumin.
AB - The unfolding of the reduced human serum albumin (HSA) was simulated by
generating four molecular dynamics (MD) trajectories of 160 ns each at 350, 375,
400, and 425 K, respectively. A principal components analysis (PCA) was performed
on the four trajectories. Based on this analysis, 17 representative protein
conformers were identified and subsequently used to construct a sequence of
partially unfolded structures. They were ordered according to their decreasing
alpha-helix fractions. The structural evolution in this unfolding sequence was
found to be continuous at global but also at local level supporting the
hypothesis that the protein unfolding pathway is not significantly dependent on
the simulation temperature. As a result, the alpha-helix fraction of the protein
appears to be a good reaction coordinate for the unfolding process, as it was
previously suggested by experiments. Based on this observation, two conformers in
the unfolding sequence were predicted to be close to the equilibrium structure of
reduced HSA thus providing a first theoretical model for this protein form.
PMID- 25851109
TI - Accuracy of 3D dual echo steady state (DESS) MR arthrography to quantify
acetabular cartilage thickness.
AB - PURPOSE: To deploy and quantify the accuracy of 3D dual echo steady state (DESS)
MR arthrography with hip traction to image acetabular cartilage. Clinical
magnetic resonance imaging (MRI) sequences used to image hip cartilage often have
reduced out-of-plane resolution and may lack adequate signal-to-noise to image
cartilage. MATERIALS AND METHODS: Saline was injected into four cadaver hips
placed under traction. 3D DESS MRI scans were obtained before and after cores of
cartilage were harvested from the acetabulum; the two MRIs were spatially aligned
to reference core positions. The thickness of cartilage cores was measured under
microscopy to serve as the reference standard. 3D reconstructions of cartilage
and subchondral bone were generated using automatic and semiautomatic image
segmentation. Cartilage thickness estimated from the 3D reconstructions was
compared to physical measurements using Bland-Altman plots. RESULTS: As revealed
by the automatic segmentation mask, saline imbibed the joint space throughout the
articulating surface, with the exception of the posteroinferior region in two
hips. Locations where air bubbles were introduced and regions of suspected low
density bone disrupted an otherwise smooth automatic segmentation mask. Automatic
and semiautomatic segmentation yielded a bias +/- repeatability coefficient (95%
limits of agreement) of 0.10 +/- 0.51 mm (-0.41 to 0.61 mm) and 0.06 +/- 0.43 mm
(-0.37 to 0.49 mm), respectively. CONCLUSION: Cartilage thickness can be
estimated to within ~0.5 mm of the physical value with 95% confidence using 3D
reconstructions of 3D DESS MR arthrography images. Manual correction of the
automatic segmentation mask may improve reconstruction accuracy.
PMID- 25851110
TI - Resveratrol reduces amyloid-beta (Abeta1-42)-induced paralysis through targeting
proteostasis in an Alzheimer model of Caenorhabditis elegans.
AB - PURPOSE: Resveratrol is a polyphenol present in red wine for which the capability
of directly interfering with the hallmark of Alzheimer's disease (AD), i.e. toxic
beta-amyloid protein (Abeta) aggregation, has been shown recently. Since the
stimulation of proteostasis could explain reduced Abeta-aggregation, we searched
for proteostasis targets of resveratrol. METHODS: The transgenic Caenorhabditis
elegans strain CL2006, expressing Abeta1-42 under control of a muscle-specific
promoter and responding to Abeta-toxicity with paralysis, was used as a model.
Target identification was accomplished through specific knockdowns of
proteostasis genes by RNA interference. Effects of resveratrol on protein
aggregation were identified using ProteoStat((r)) Detection Reagent, and
activation of proteasomal degradation by resveratrol was finally proven using a
specific fluorogenic peptide substrate. RESULTS: Resveratrol at a concentration
of 100 uM caused a 40 % decrease in paralysis. UBL-5 involved in unfolded protein
response (UPR) in mitochondria proved to be necessary for the prevention of Abeta
toxicity by resveratrol. Also XBP-1, which represents an endoplasmic reticulum
resident factor involved in UPR, was identified to be necessary for the effects
of resveratrol. Regarding protein degradation pathways, the inhibition of
macroautophagy and chaperone-mediated autophagy prevented resveratrol from
reducing paralysis as did the inhibition of proteasomal degradation. Finally,
resveratrol reduced the amount of lysosomes, suggesting increased flux of
proteins through the autophagy pathways and activated proteasomal degradation.
CONCLUSIONS: Resveratrol reduces the Abeta-induced toxicity in a C. elegans model
of AD by targeting specific proteins involved in proteostasis and thereby reduces
the amount of aggregated Abeta.
PMID- 25851112
TI - Erratum to: Modified technique of levator plication for the correction of Marcus
Gunn jaw-winking ptosis: a case series.
PMID- 25851111
TI - Overlap between linear scleroderma, progressive facial hemiatrophy and immune
inflammatory encephalitis in a paediatric cohort.
AB - Linear scleroderma en coup the sabre (LSCS), progressive facial hemiatrophy (PFH)
and autoimmune encephalitis are distinct clinical entities, although patients
with overlapping features have been reported. We performed a multicenter
retrospective review of a series of children with LSCS and/or PFH to explore the
relation between these entities. The files of 16 children were reviewed, 11
presented with LSCS, 5 with PFH, with time overlapping cutaneous features were
seen. Extracutaneous signs were found in both groups. ANA were present in more
than 50 % of patients. Almost half of our patients presented with CNS
manifestations comprising unilateral headache, migraine and epilepsy with or
without abnormalities on MRI. Brain biopsy in one patient was consistent with
Rasmussen encephalitis. In two other children, associated autoimmune
manifestations were present. CONCLUSION: Our patient cohort brings more arguments
to consider LSCS and PFH as a single disease entity with LSCS and superficial
skin involvement at one end of the spectrum and PFH with involvement of
subcutaneous deep tissue at the other end. In both entities, encephalitis can be
observed. Our findings of circulating ANA, intradermal lymphocytes and IgG,
intrathecal IgG production and clinical improvement with immunosuppressive
therapy endorse the concept of a possible common immune-inflammatory
pathogenesis. WHAT IS KNOWN: * LSCS, PFH and immune-inflammatory encephalitis are
distinct clinical entities, but patients with overlapping features have been
reported. WHAT IS NEW: * We present a unique paediatric cohort with LSCS, PFH
and/or encephalitis. * We endorse the concept of a common immune-inflammatory
disease process.
PMID- 25851113
TI - Label-free quartz crystal microbalance with dissipation monitoring of resveratrol
effect on mechanical changes and folate receptor expression levels of living MCF
7 cells: a model for screening of drugs.
AB - Quartz crystal microbalance with dissipation (QCM-D) monitoring was used for real
time and label-free detection of changes and folate receptor (FR) expression
levels on living MCF-7 cells for evaluating the anticancer activity of
resveratrol. Here, the mechanical changes of cellular responses to resveratrol
were tracked by a poly(l-lysine) (PLL) modified QCM-D sensor, and the inhibition
effect of resveratrol on FR expression levels on MCF-7 cells was monitored by
chitosan-folic acid (CS-FA) composite membrane functionalized Au substrate for
the first time. Changes in morphology and the cellular state of MCF-7 cells
stimulated by resveratrol at different concentrations were detected by inverted
fluorescence microscopy and flow cytometry. Atomic force microscopy confirmed
that resveratrol influenced the cellular mechanical properties. The results
indicated that the MCF-7 cells lose their original elasticity and increase their
stiffness induced by resveratrol. It was further observed by confocal
fluorescence imaging that resveratrol reduced the FR expression levels on the
living cells surface. This study established a typical model of the QCM-D
biosensor to evaluate the protein biomarker expression levels on the cells
surface. QCM-D, which was used to investigate potential targets for an antitumor
drug on living cells and realize a better understanding of the drug action
mechanism, was expected to be developed into a promising tool for the screening
of drugs.
PMID- 25851114
TI - Diagnostic yield of echocardiography in cancer patients with ischemic stroke.
AB - The yield of echocardiography in cancer patients with acute ischemic stroke is
unknown. We identified adult patients with active systemic cancer diagnosed with
acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009 who
underwent transthoracic (TTE) or transesophageal echocardiography (TEE). Two
neurologists independently reviewed all clinical data, including TTE and TEE
reports, and adjudicated whether echocardiographic studies revealed a definite or
possible source of stroke according to pre-defined criteria. Patients were
classified as having suspected cardioembolic strokes if imaging showed embolic
appearing infarcts in more than one vascular territory. Among 220 patients with
cancer and ischemic stroke who underwent echocardiography, 216 (98%) had TTE and
37 (17%) had TEE. TTE revealed a definite source in 15 (7%, 95% CI 4-10%)
patients and a possible source in 42 (19%, 95% CI 14-25%), while TEE revealed a
definite source in 10 (27%, 95% CI 12-42%) patients and a possible source in 14
(38%, 95% CI 21-54%). In 92 patients with suspected cardioembolic strokes who
underwent TTE, 6 (7%, 95% CI 1-12%) had a definite source, including 4 with
marantic endocarditis, and 20 (22%, 95% CI 13-30%) had a possible source. Twenty
one of these patients also underwent TEE, which demonstrated a definite or
possible source in 16 (76%, 95% CI 56-96%) patients, including marantic
endocarditis in 4 (19%). The yield of TTE for detecting marantic endocarditis and
other cardiac sources of stroke in cancer patients is low, but TEE may provide a
higher yield in targeted patients.
PMID- 25851115
TI - Development and psychometric evaluation of patient needs assessment in palliative
care (PNAP) instrument.
AB - OBJECTIVE: Although assessment of palliative patients' needs is a key issue in
palliative care, a suitable instrument for identification of such needs is not
available in Central European countries. Our objectives were to produce an
adequate tool for identifying the importance and satisfaction of palliative
patients' needs and to verify its psychometric properties. METHOD: The patient
needs assessment in palliative care (PNAP) instrument was constructed based on a
literature review and qualitative research (focus groups, n = 5). The
psychometric properties of the questionnaire were verified by a cross-sectional
study. The convergent validity of the questionnaire was determined by
confirmatory factor analysis. Furthermore, internal consistency, test-retest
reliability, and construct validity were also tested. The qualitative research
group comprised 30 participants (27 experts in palliative care, 1 patient, and 2
family members). Psychometric properties were evaluated in a group of 349
hospital inpatients terminally ill with chronic disease or cancer and receiving
palliative care. RESULTS: Based on the qualitative data analysis, a questionnaire
was constructed that contained 42 items grouped into 5 domains. When testing the
psychometric properties of the questionnaire, a new model containing 40 items in
7 domains was produced. Cronbach's alpha for the entire PNAP questionnaire was
0.89 on the importance scale and 0.80 on the satisfaction scale. Test-retest
reliability was higher than 0.7 for all domains in both scales. SIGNIFICANCE OF
RESULTS: The results of tests on the psychometric properties of the PNAP
questionnaire showed at least satisfactory validity and reliability, and it can
be employed to assess the needs of palliative care patients in Central European
countries.
PMID- 25851116
TI - Why should governments invest in antibiotic drug discovery against multi-drug
resistant bacteria?
PMID- 25851117
TI - Crofelemer: In HIV Associated Diarrhea and Secretory Diarrhea - A Patent
Perspective.
AB - PURPOSE: Diarrhea and dehydration caused by enteric infections is a major factor
of morbidity and mortality worldwide. Secretory diarrhea can be devastating
especially among infants, children, and HIV infected people and can result in
death of more than 50% of its victims for without adequate rehydration, patients
are at maximum risk during the first 6-18 hours. Hence, it is a leading cause of
morbidity and mortality worldwide. Diarrhea is experienced by over 50% of AIDS
patients at some time or other during the course of their illness, which is an
important cause of increased morbidity and mortality in them. Currently, the
standard-of-care therapy focuses only on rehydration therapy to combat
dehydration and antibiotic therapy that targets the infectious agent only.
Though, antimicrobial drugs have been the key treatment for diarrhea but, with
the emergence of resistant strains the search for novel targets/drugs is on, for
diarrhea still continues to kill millions. METHODS: A literature search was done
using secretory diarrhea and Crofelemer, as key words using PubMed (Medline),
ProQuest, Cochrane Library, Medscape and Google Scholar search engines from
January 2012 to December 2014. The types of articles included in this review were
original research, review papers, recent patents and editorials from various
medical schools across the globe. Though, it was practically not possible to
include all studies, one can marvel at all the proclaimed mechanism of action of
Crofelemer in this study. RESULTS: Crofelemer, a channel blocker of intestinal
chloride channels such as the Cystic Fibrosis Transmembrane Conductance Regulator
(CFTR) and the Calcium Activated Chloride Channels (CaCCs) plays significant
roles in providing symptomatic relief in secretory diarrhea. CONCLUSION:
Crofelemer is a first-in-class agent that possesses a unique mechanism of action
through dual inhibition of both the intestinal chloride channels in secretory
diarrhea.
PMID- 25851118
TI - Making meaning of pumping for mothers of infants with congenital diaphragmatic
hernia.
AB - OBJECTIVE: To describe the process of initiation and maintenance of milk supply
and potential transition to direct breastfeeding among mother/infant dyads with
infants with congenital diaphragmatic hernia (CDH). SETTING: A Level-III neonatal
intensive care unit. PARTICIPANTS: Eleven mother/infant dyads with infants with
CDH. METHODS: Prospective, longitudinal qualitative descriptive design.
Semistructured interviews were conducted over the course of the NICU stay.
Conventional content analysis was used. RESULTS: Human milk oral care emerged
from the interview data as a strong facilitating factor to encouraging mothers to
continue pumping during hospitalization. Four main themes emerged regarding the
importance and value of human milk oral care for the mothers in relation to
pumping and maintenance of milk supply: (a) It motivates me; (b) I'm a part of my
baby getting better; (c) We do it together, and (d) We're getting somewhere.
CONCLUSIONS: The findings of this study reflect the importance and value of human
milk oral care as a driving factor to motivate mothers to maintain milk supply
during the critical time when the infant with CDH is not able to take in enteral
nutrition and throughout the hospital stay.
PMID- 25851119
TI - Pharmacokinetics of minocycline in domestic cats.
AB - OBJECTIVES: Recently, the increased cost and decreased availability of
doxycycline has sparked an interest in using minocycline as an alternative. The
purpose of this study was to determine the pharmacokinetics of minocycline in
domestic cats in order to facilitate dosage decisions. METHODS: Purpose-bred,
young adult cats were administered a single dose of either intravenous (IV; n =
4; 5 mg/kg) or oral (n = 6; 50 mg/cat) minocycline. Blood was collected from each
at intervals up to 24 h afterwards. Minocycline was measured using high
performance liquid chromatography with ultraviolet detection. A one-compartment
pharmacokinetic model was fit to the oral data and a two-compartment model to the
IV data via a computer program. Plasma protein binding was measured by fortifying
blank plasma from untreated healthy cats with minocycline at two concentrations
and applying an ultracentrifugation method. RESULTS: Two cats became transiently
lethargic and tachypneic during IV drug infusion. One cat vomited 6.0 h after
infusion, and two cats vomited either 1.5 h or ~5.0 h after oral drug
administration. The mean oral dose administered was 13.9 +/- 0.47 mg/kg. Oral
bioavailability was approximately 62%. Plasma protein binding was 60% at 5 ug/ml
and 46% at 1 MUg/ml. After IV administration, elimination half-life (t(1/2)),
apparent volume of distribution at steady-state, and systemic clearance were 6.7
h (coefficient of variation [CV] 14.4%), 1.5 l/kg (CV 34.5%) and 2.9 ml/kg/min
(CV 40.8%), respectively. After oral administration the terminal t(1/2) and peak
concentration (Cmax) were 6.3 h (CV 9%) and 4.77 ug/ml (CV 36%), respectively.
CONCLUSIONS AND RELEVANCE: Because most bacteria will have a minimum inhibitory
concentration of ?0.5 MUg/ml, an oral dose of 8.8 mg/kg q24h would be adequate to
meet pharmacokinetic-pharmacodynamic targets after adjusting for protein binding.
Although some gastrointestinal upset may occur, one 50 mg capsule orally q24h
would provide appropriate dosing for most cats.
PMID- 25851120
TI - Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue
engineering.
AB - Engineered tissue constructs have the potential to augment or replace whole organ
transplantation for the treatment of liver failure. Poly(ethylene glycol) (PEG)
based systems are particularly promising for the construction of engineered liver
tissue due to their biocompatibility and amenability to modular addition of
bioactive factors. To date, primary hepatocytes have been successfully
encapsulated in non-degradable hydrogels based on PEG-diacrylate (PEGDA). In this
study, we describe a hydrogel system based on PEG-diacrylamide (PEGDAAm)
containing matrix-metalloproteinase sensitive (MMP-sensitive) peptide in the
hydrogel backbone that is suitable for hepatocyte culture both in vitro and after
implantation. By replacing hydrolytically unstable esters in PEGDA with amides in
PEGDAAm, resultant hydrogels resisted non-specific hydrolysis, while still
allowing for MMP-mediated hydrogel degradation. Optimization of polymerization
conditions, hepatocellular density, and multicellular tissue composition
modulated both the magnitude and longevity of hepatic function in vitro.
Importantly, hepatic PEGDAAm-based tissues survived and functioned for over 3
weeks after implantation ectopically in the intraperitoneal (IP) space of nude
mice. Together, these studies suggest that MMP-sensitive PEGDAAm-based hydrogels
may be a useful material system for applications in tissue engineering and
regenerative medicine. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part
A: 103A: 3331-3338, 2015.
PMID- 25851122
TI - Recurrent venous thromboembolism in anticoagulated patients with cancer:
management and short-term prognosis.
AB - BACKGROUND: Recommendations for management of cancer-related venous
thromboembolism (VTE) in patients already receiving anticoagulant therapy are
based on low-quality evidence. This international registry sought to provide more
information on outcomes after a breakthrough VTE in relation to anticoagulation
strategies. METHODS: Patients with cancer and VTE despite anticoagulant therapy
were reported to the registry. Data on treatments, VTE events, major bleeding,
residual thrombosis symptoms and death were collected for the following 3 months.
Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes
with different treatment strategies were compared with Cox proportional hazards
regression. RESULTS: We registered 212 patients with breakthrough VTE. Of those,
59% had adenocarcinoma and 73% had known metastases. At the time of the
breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a
vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After
breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased
in 31%, switched to another drug in 24%; and other management in 11%. During the
following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of
the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence
was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95%
confidence interval [CI], 0.11-0.70) but similar with unchanged or increased
anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not
increase significantly with dose escalation. CONCLUSION: Morbidity and mortality
are high after recurrence of cancer-related VTE despite anticoagulation. Further
treatment appears to be more effective with LMWH than with a VKA.
PMID- 25851123
TI - Methodological considerations on push-out tests in Endodontics.
PMID- 25851124
TI - New directions in qualitative research in psychology.
AB - Qualitative Research gains increasing popularity in the field of Psychology. With
the renewed interest, there are, however, also some risks related to the
overhomogenization and increasing standardization of qualitative methods. This
special issue is dedicated to clarify some of the existing misconceptions of
qualitative research and to discuss its potentials for the field of psychology in
light of recent endeavors to overcome paradigmatic battles and a re-orientation
to the specifities of psychology. The issue comprises a discussion from workshop
on the future of qualitative research in psychology organized at Aalborg
University, and several contributions that resulted from it.
PMID- 25851125
TI - Notch Receptor-Ligand Engagement Maintains Hematopoietic Stem Cell Quiescence and
Niche Retention.
AB - Notch is long recognized as a signaling molecule important for stem cell self
renewal and fate determination. Here, we reveal a novel adhesive role of Notch
ligand engagement in hematopoietic stem and progenitor cells (HSPCs). Using mice
with conditional loss of O-fucosylglycans on Notch EGF-like repeats important for
the binding of Notch ligands, we report that HSPCs with faulty ligand binding
ability display enhanced cycling accompanied by increased egress from the marrow,
a phenotype mainly attributed to their reduced adhesion to Notch ligand
expressing stromal cells and osteoblastic cells and their altered occupation in
osteoblastic niches. Adhesion to Notch ligand-bearing osteoblastic or stromal
cells inhibits wild type but not O-fucosylglycan-deficient HSPC cycling,
independent of RBP-JK -mediated canonical Notch signaling. Furthermore, Notch
ligand neutralizing antibodies induce RBP-JK -independent HSPC egress and
enhanced HSPC mobilization. We, therefore, conclude that Notch receptor-ligand
engagement controls HSPC quiescence and retention in the marrow niche that is
dependent on O-fucosylglycans on Notch.
PMID- 25851126
TI - Effects of cyclodextrins on GM1-gangliosides in fibroblasts from GM1
gangliosidosis patients.
AB - OBJECTIVES: GM1-gangliosidosis is an inherited disorder characterized by the
accumulation of GM1-gangliosides in many tissues and organs, particularly in the
brain. Currently, there is no treatment available for patients with ganglioside
storage diseases. Therefore, we investigated the effects of cyclodextrins (CyDs)
on the GM1-ganglioside level in EA1 cells, fibroblasts from patients with GM1
gangliosidosis. METHODS: The concentrations of cholesterol and phospholipids in
supernatants were determined by Cholesterol E-test Wako and Phospholipid C-test
Wako, respectively. The effects of CyDs on GM1-ganglioside levels in EA1 cells
using fluorescence-labelled cholera toxin B-subunit, which can bind to GM1
gangliosides specifically, were investigated by flow cytometry and confocal laser
scanning microscopy. KEY FINDINGS: The treatment with methylated CyDs,
hydroxypropylated CyDs and branched CyDs decreased GM1-ganglioside levels in EA1
cells at 1 mm for 24 h. Unexpectedly, there was no significant change in the
efflux of cholesterol or phospholipids from the cells after treatment with CyDs
under the same experimental conditions, indicating that the efflux of membrane
components is not associated with down-regulation of GM1-ganglioside levels in
EA1 cells upon CyDs treatment. CONCLUSIONS: CyDs may have the potential as drugs
for GM1-gangliosidosis, although the mechanism should be thereafter clarified.
PMID- 25851127
TI - Quest for highly connected metal-organic framework platforms: rare-earth
polynuclear clusters versatility meets net topology needs.
AB - Gaining control over the assembly of highly porous rare-earth (RE) based metal
organic frameworks (MOFs) remains challenging. Here we report the latest
discoveries on our continuous quest for highly connected nets. The topological
exploration based on the noncompatibility of a 12-connected RE polynuclear
carboxylate-based cluster, points of extension matching the 12 vertices of the
cuboctahedron (cuo), with 3-connected organic ligands led to the discovery of two
fascinating and highly connected minimal edge-transitive nets, pek and aea. The
reduced symmetry of the employed triangular tricarboxylate ligand, as compared to
the prototype highly symmetrical 1,3,5-benzene(tris)benzoic acid guided the
concurrent occurrence of nonanuclear [RE9(MU3-OH)12(MU3-O)2(O2C-)12] and
hexanuclear [RE6(OH)8(O2C-)8] carboxylate-based clusters as 12-connected and 8
connected molecular building blocks in the structure of a 3-periodic pek-MOF
based on a novel (3,8,12)-c trinodal net. The use of a tricarboxylate ligand with
modified angles between carboxylate moieties led to the formation of a second MOF
containing solely nonanuclear clusters and exhibiting once more a novel and a
highly connected (3,12,12)-c trinodal net with aea topology. Notably, it is the
first time that RE-MOFs with double six-membered ring (d6R) secondary building
units are isolated, representing therefore a critical step forward toward the
design of novel and highly coordinated materials using the supermolecular
building layer approach while considering the d6Rs as building pillars. Lastly,
the potential of these new MOFs for gas separation/storage was investigated by
performing gas adsorption studies of various probe gas molecules over a wide
range of pressures. Noticeably, pek-MOF-1 showed excellent volumetric CO2 and CH4
uptakes at high pressures.
PMID- 25851129
TI - Epoch-based likelihood models reveal no evidence for accelerated evolution of
viviparity in squamate reptiles in response to cenozoic climate change.
AB - A broad scale analysis of the evolution of viviparity across nearly 4,000 species
of squamates revealed that origins increase in frequency toward the present,
raising the question of whether rates of change have accelerated. We here use
simulations to show that the increased frequency is within the range expected
given that the number of squamate lineages also increases with time. Novel, epoch
based methods implemented in BEAST (which allow rates of discrete character
evolution to vary across time-slices) also give congruent results, with recent
epochs having very similar rates to older epochs. Thus, contrary to expectations,
there was no accelerated burst of origins of viviparity in response to global
cooling during the Cenozoic or glacial cycles during the Plio-Pleistocene.
However, if one accepts the conventional view that viviparity is more likely to
evolve than to be lost, and also the evidence here that viviparity has evolved
with similar regularity throughout the last 200 Ma, then the absence of large,
ancient clades of viviparous squamates (analogs to therian mammals) requires
explanation. Viviparous squamate lineages might be more prone to extinction than
are oviparous lineages, due to their prevalance at high elevations and latitudes
and thus greater susceptibility to climate fluctuations. If so, the directional
bias in character evolution would be offset by the bias in extinction rates.
PMID- 25851130
TI - Farmed and wild sea bass (Dicentrarchus labrax) volatile metabolites: a
comparative study by SPME-GC/MS.
AB - BACKGROUND: Farmed and wild European sea bass (Dicentrarchus labrax) could be
distinguished by its volatile metabolites, an issue not addressed until now. The
aim of this work was to study these metabolites by solid-phase microextraction
followed by gas chromatography/mass spectrometry (SPME-GC/MS). RESULTS: Both
farmed and wild sea bass have a great number of volatile metabolites, most of
them being in low concentrations. These include alcohols, aldehydes, ketones,
alkylfurans, acids, aliphatic and aromatic hydrocarbons, terpenes, sulfur and
nitrogen derivatives, 2,6-di-tert-butyl-4-methylphenol and one derived compound,
as well as 2,4,7,9-tetramethyl-5-decyne-4,7-diol, this latter compound presumably
resulting from environmental contamination. Important differences have been
detected between both types of sea bass, and also among individuals inside each
group. Farmed specimens are richer in volatile metabolites than the wild
counterparts; however, these latter, in general, contain a high number and
abundance of metabolites resulting from microbial and enzymatic non-oxidative
activity than the former. CONCLUSIONS: Clear differences in the volatile
metabolites of wild and farmed sea bass have been found. A great deal of valuable
information on sea bass volatile metabolites has been obtained, which can be
useful in understanding certain aspects of the quality and safety of raw and
processed sea bass.
PMID- 25851131
TI - Cochliopodium arabianum n. sp. (Amorphea, Amoebozoa).
AB - A new species of Cochliopodium isolated from freshwater at Arabia Lake in
Lithonia, GA, USA is described based on light microscopic morphology, fine
structure, and molecular genetic evidence. Cochliopodium arabianum n. sp.,
previously labeled as "isolate Con1" in prior publications, has been shown to
group within the genus Cochliopodium in our molecular phylogenetic analysis.
Light microscopy and fine structure evidence indicates the new isolate not only
shares characters of the genus but also unique distinctive features.
Cochliopodium arabianum n. sp. is typically round when stationary; or oval to
sometimes broadly flabellate or triangular in shape during locomotion, with
average length of 35 MUm and breadth of 51 MUm. Fine structure evidence indicates
C. arabianum n. sp. has tower-like scales, lacking a terminal spine, sharing high
similarity with its closest relative C. actinophorum. However, the scales of C.
arabianum n. sp. are unique in height and the breadth of the base plate. Both
morphological and molecular data, including SSU-rDNA and COI, indicate that this
new species falls in a clade sufficiently different from other species to suggest
that it is a valid new species.
PMID- 25851132
TI - Does long-term cultivation of saplings under elevated CO2 concentration influence
their photosynthetic response to temperature?
AB - BACKGROUND AND AIMS: Plants growing under elevated atmospheric CO2 concentrations
often have reduced stomatal conductance and subsequently increased leaf
temperature. This study therefore tested the hypothesis that under long-term
elevated CO2 the temperature optima of photosynthetic processes will shift
towards higher temperatures and the thermostability of the photosynthetic
apparatus will increase. METHODS: The hypothesis was tested for saplings of
broadleaved Fagus sylvatica and coniferous Picea abies exposed for 4-5 years to
either ambient (AC; 385 umol mol(-1)) or elevated (EC; 700 umol mol(-1)) CO2
concentrations. Temperature response curves of photosynthetic processes were
determined by gas-exchange and chlorophyll fluorescence techniques. KEY RESULTS:
Initial assumptions of reduced light-saturated stomatal conductance and increased
leaf temperatures for EC plants were confirmed. Temperature response curves
revealed stimulation of light-saturated rates of CO2 assimilation (Amax) and a
decline in photorespiration (RL) as a result of EC within a wide temperature
range. However, these effects were negligible or reduced at low and high
temperatures. Higher temperature optima (Topt) of Amax, Rubisco carboxylation
rates (VCmax) and RL were found for EC saplings compared with AC saplings.
However, the shifts in Topt of Amax were instantaneous, and disappeared when
measured at identical CO2 concentrations. Higher values of Topt at elevated CO2
were attributed particularly to reduced photorespiration and prevailing
limitation of photosynthesis by ribulose-1,5-bisphosphate (RuBP) regeneration.
Temperature response curves of fluorescence parameters suggested a negligible
effect of EC on enhancement of thermostability of photosystem II photochemistry.
CONCLUSIONS: Elevated CO2 instantaneously increases temperature optima of Amax
due to reduced photorespiration and limitation of photosynthesis by RuBP
regeneration. However, this increase disappears when plants are exposed to
identical CO2 concentrations. In addition, increased heat-stress tolerance of
primary photochemistry in plants grown at elevated CO2 is unlikely. The
hypothesis that long-term cultivation at elevated CO2 leads to acclimation of
photosynthesis to higher temperatures is therefore rejected. Nevertheless,
incorporating acclimation mechanisms into models simulating carbon flux between
the atmosphere and vegetation is necessary.
PMID- 25851133
TI - Can the exceptional chilling tolerance of C4 photosynthesis found in Miscanthus *
giganteus be exceeded? Screening of a novel Miscanthus Japanese germplasm
collection.
AB - BACKGROUND AND AIMS: A clone of the hybrid perennial C4 grass Miscanthus *
giganteus (Mxg) is known for achieving exceptionally high rates of leaf CO2
uptake during chilling. This is a requisite of success in the early spring, as is
the ability of the leaves to survive occasional frosts. The aim of this study was
to search for genotypes with greater potential than Mxg for photosynthesis and
frost survival under these conditions. METHODS: A total of 864 accessions
representing 164 local populations of M. sacchariflorus (Msa), M. sinensis (Msi)
and M. tinctorius (Mti) collected across Japan were studied. Accessions whose
leaves survived a natural late frost in the field were screened for high maximum
photosystem II efficiency (Fv/Fm) following chilling weather, as an indicator of
their capacity for light-limited photosynthesis. Those showing the highest Fv/Fm
were transferred to a high-light-controlled environment and maintained at
chilling temperatures, where they were further screened for their capacities for
high-light-limited and light-saturated leaf uptake of CO2 (PhiCO2,max and Asat,
respectively). KEY RESULTS: For the first time, relatives of Mxg with
significantly superior capacities for photosynthesis at chilling temperatures
were identified. Msa accession '73/2' developed leaves in the spring that
survived night-time frost, and during growth under chilling maintained a
statistically significant 79 % higher PhiCO2,max, as a measure of light-limited
photosynthesis, and a 70 % higher Asat, as a measure of light-saturated
photosynthesis. A second Msa accession, '73/3' also showed significantly higher
rates of leaf uptake of CO2. CONCLUSIONS: As remarkable as Mxg has proved in its
chilling tolerance of C4 photosynthesis, this study shows that there is still
value and potential in searching for yet more superior tolerance. Msa accession
'73/2' shows rates of light-limited and light-saturated photosynthesis at
chilling temperatures that are comparable with those of the most cold-tolerant C3
species. This adds further proof to the thesis that C4 photosynthesis is not
inherently limited to warm climates.
PMID- 25851134
TI - What functional strategies drive drought survival and recovery of perennial
species from upland grassland?
AB - BACKGROUND AND AIMS: Extreme climatic events such as severe droughts are expected
to increase with climate change and to limit grassland perennity. The present
study aimed to characterize the adaptive responses by which temperate herbaceous
grassland species resist, survive and recover from a severe drought and to
explore the relationships between plant resource use and drought resistance
strategies. METHODS: Monocultures of six native perennial species from upland
grasslands and one Mediterranean drought-resistant cultivar were compared under
semi-controlled and non-limiting rooting depth conditions. Above- and below
ground traits were measured under irrigation in spring and during drought in
summer (50 d of withholding water) in order to characterize resource use and
drought resistance strategies. Plants were then rehydrated and assessed for
survival (after 15 d) and recovery (after 1 year). KEY RESULTS: Dehydration
avoidance through water uptake was associated with species that had deep roots
(>1.2 m) and high root mass (>4 kg m(-3)). Cell membrane stability ensuring
dehydration tolerance of roots and meristems was positively correlated with
fructan content and negatively correlated with sucrose content. Species that
survived and recovered best combined high resource acquisition in spring (leaf
elongation rate >9 mm d(-1) and rooting depth >1.2 m) with both high dehydration
avoidance and tolerance strategies. CONCLUSIONS: Most of the native forage
species, dominant in upland grassland, were able to survive and recover from
extreme drought, but with various time lags. Overall the results suggest that the
wide range of interspecific functional strategies for coping with drought may
enhance the resilience of upland grassland plant communities under extreme
drought events.
PMID- 25851135
TI - From observations to experiments in phenology research: investigating climate
change impacts on trees and shrubs using dormant twigs.
AB - BACKGROUND AND AIMS: Climate change is advancing the leaf-out times of many plant
species and mostly extending the growing season in temperate ecosystems.
Laboratory experiments using twig cuttings from woody plant species present an
affordable, easily replicated approach to investigate the relative importance of
factors such as winter chilling, photoperiod, spring warming and frost tolerance
on the leafing-out times of plant communities. This Viewpoint article
demonstrates how the results of these experiments deepen our understanding beyond
what is possible via analyses of remote sensing and field observation data, and
can be used to improve climate change forecasts of shifts in phenology, ecosystem
processes and ecological interactions. SCOPE: The twig method involves cutting
dormant twigs from trees, shrubs and vines on a single date or at intervals over
the course of the winter and early spring, placing them in containers of water in
controlled environments, and regularly recording leaf-out, flowering or other
phenomena. Prior to or following leaf-out or flowering, twigs may be assigned to
treatment groups for experiments involving temperature, photoperiod, frost,
humidity and more. Recent studies using these methods have shown that winter
chilling requirements and spring warming strongly affect leaf-out and flowering
times of temperate trees and shrubs, whereas photoperiod requirements are less
important than previously thought for most species. Invasive plant species have
weaker winter chilling requirements than native species in temperate ecosystems,
and species that leaf-out early in the season have greater frost tolerance than
later leafing species. CONCLUSIONS: This methodology could be extended to
investigate additional drivers of leaf-out phenology, leaf senescence in the
autumn, and other phenomena, and could be a useful tool for education and
outreach. Additional ecosystems, such as boreal, southern hemisphere and sub
tropical forests, could also be investigated using dormant twigs to determine the
drivers of leaf-out times and how these ecosystems will be affected by climate
change.
PMID- 25851136
TI - Extreme defoliation reduces tree growth but not C and N storage in a winter
deciduous species.
AB - BACKGROUND AND AIMS: There is a growing concern about how forests will respond to
increased herbivory associated with climate change. Carbon (C) and nitrogen (N)
limitation are hypothesized to cause decreasing growth after defoliation, and
eventually mortality. This study examines the effects of a natural and massive
defoliation by an insect on mature trees' C and N storage, which have rarely been
studied together, particularly in winter-deciduous species. METHODS: Survival,
growth rate, carbon [C, as non-structural carbohydrate (NSC) concentration] and
nitrogen (N) storage, defences (tannins and total polyphenols), and re-foliation
traits were examined in naturally defoliated and non-defoliated adult trees of
the winter-deciduous temperate species Nothofagus pumilio 1 and 2 years after a
massive and complete defoliation caused by the caterpillar of Ormiscodes
amphimone (Saturniidae) during summer 2009 in Patagonia. KEY RESULTS: Defoliated
trees did not die but grew significantly less than non-defoliated trees for at
least 2 years after defoliation. One year after defoliation, defoliated trees had
similar NSC and N concentrations in woody tissues, higher polyphenol
concentrations and lower re-foliation than non-defoliated trees. In the second
year, however, NSC concentrations in branches were significantly higher in
defoliated trees while differences in polyphenols and re-foliation disappeared
and decreased, respectively. CONCLUSIONS: The significant reduction in growth
following defoliation was not caused by insufficient C or N availability, as
frequently assumed; instead, it was probably due to growth limitations due to
factors other than C or N, or to preventative C allocation to storage. This study
shows an integrative approach to evaluating plant growth limitations in response
to disturbance, by examining major resources other than C (e.g. N), and other C
sinks besides storage and growth (e.g. defences and re-foliation).
PMID- 25851137
TI - A theoretical approach to the relationship between wettability and surface
microstructures of epidermal cells and structured cuticles of flower petals.
AB - BACKGROUND AND AIMS: The epidermal surface of a flower petal is composed of
convex cells covered with a structured cuticle, and the roughness of the surface
is related to the wettability of the petal. If the surface remains wet for an
excessive amount of time the attractiveness of the petal to floral visitors may
be impaired, and adhesion of pathogens may be promoted. However, it remains
unclear how the epidermal cells and structured cuticle contribute to surface
wettability of a petal. METHODS: By considering the additive effects of the
epidermal cells and structured cuticle on petal wettability, a thermodynamic
model was developed to predict the wetting mode and contact angle of a water
droplet at a minimum free energy. Quantitative relationships between petal
wettability and the geometries of the epidermal cells and the structured cuticle
were then estimated. Measurements of contact angles and anatomical traits of
petals were made on seven herbaceous species commonly found in alpine habitats in
eastern Nepal, and the measured wettability values were compared with those
predicted by the model using the measured geometries of the epidermal cells and
structured cuticles. KEY RESULTS: The model indicated that surface wettability
depends on the height and interval between cuticular steps, and on a height-to
width ratio for epidermal cells if a thick hydrophobic cuticle layer covers the
surface. For a petal epidermis consisting of lenticular cells, a repellent
surface results when the cuticular step height is greater than 0.85 um and the
height-to-width ratio of the epidermal cells is greater than 0.3. For an
epidermis consisting of papillate cells, a height-to-width ratio of greater than
1.1 produces a repellent surface. In contrast, if the surface is covered with a
thin cuticle layer, the petal is highly wettable (hydrophilic) irrespective of
the roughness of the surface. These predictions were supported by the
measurements of petal wettability made on flowers of alpine species. CONCLUSIONS:
The results indicate that surface roughness caused by epidermal cells and a
structured cuticle produces a wide range of petal wettability, and that this can
be successfully modelled using a thermodynamic approach.
PMID- 25851138
TI - Modelling snow cover duration improves predictions of functional and taxonomic
diversity for alpine plant communities.
AB - BACKGROUND AND AIMS: Quantifying relationships between snow cover duration and
plant community properties remains an important challenge in alpine ecology. This
study develops a method to estimate spatial variation in energy availability in
the context of a topographically complex, high-elevation watershed, which was
used to test the explanatory power of environmental gradients both with and
without snow cover in relation to taxonomic and functional plant diversity.
METHODS: Snow cover in the French Alps was mapped at 15-m resolution using
Landsat imagery for five recent years, and a generalized additive model (GAM) was
fitted for each year linking snow to time and topography. Predicted snow cover
maps were combined with air temperature and solar radiation data at daily
resolution, summed for each year and averaged across years. Equivalent growing
season energy gradients were also estimated without accounting for snow cover
duration. Relationships were tested between environmental gradients and diversity
metrics measured for 100 plots, including species richness, community-weighted
mean traits, functional diversity and hyperspectral estimates of canopy
chlorophyll content. KEY RESULTS: Accounting for snow cover in environmental
variables consistently led to improved predictive power as well as more
ecologically meaningful characterizations of plant diversity. Model parameters
differed significantly when fitted with and without snow cover. Filtering solar
radiation with snow as compared without led to an average gain in R(2) of 0.26
and reversed slope direction to more intuitive relationships for several
diversity metrics. CONCLUSIONS: The results show that in alpine environments high
resolution data on snow cover duration are pivotal for capturing the spatial
heterogeneity of both taxonomic and functional diversity. The use of climate
variables without consideration of snow cover can lead to erroneous predictions
of plant diversity. The results further indicate that studies seeking to predict
the response of alpine plant communities to climate change need to consider
shifts in both temperature and nival regimes.
PMID- 25851139
TI - How tree species fill geographic and ecological space in eastern North America.
AB - BACKGROUND AND AIMS: Ecologists broadly accept that the number of species present
within a region balances regional processes of immigration and speciation against
competitive and other interactions between populations that limit distribution
and constrain diversity. Although ecological theory has, for a long time,
addressed the premise that ecological space can be filled to 'capacity' with
species, only with the availability of time-calibrated phylogenies has it been
possible to test the hypothesis that diversification slows as the number of
species in a region increases. Focusing on the deciduous trees of eastern North
America, this study tested predictions from competition theory concerning the
distribution and abundance of species. METHODS: Local assemblages of trees
tabulated in a previous study published in 1950 were analysed. Assemblages were
ordinated with respect to species composition by non-metric multidimensional
scaling (NMS). Distributions of trees were analysed by taxonomically nested
analysis of variance, discriminant analysis based on NMS scores, and canonical
correlation analysis of NMS scores and Bioclim climate variables. KEY RESULTS:
Most of the variance in species abundance and distribution was concentrated among
closely related (i.e. congeneric) species, indicating evolutionary lability.
Species distribution and abundance were unrelated to the number of close
relatives, suggesting that competitive effects are diffuse. Distances between
pairs of congeneric species in NMS space did not differ significantly from
distances between more distantly related species, in contrast to the predictions
of both competitive habitat partitioning and ecological sorting of species.
CONCLUSIONS: Eastern deciduous forests of North America do not appear to be
saturated with species. The distributions and abundances of individual species
provide little evidence of being shaped by competition from related (i.e.
ecologically similar) species and, by inference, that diversification is
constrained by interspecific competition.
PMID- 25851140
TI - Redox markers for drought-induced nodule senescence, a process occurring after
drought-induced senescence of the lowest leaves in soybean (Glycine max).
AB - BACKGROUND AND AIMS: Water is an increasingly scarce resource that limits crop
productivity in many parts of the world, and the frequency and severity of
drought are predicted to increase as a result of climate change. Improving
tolerance to drought stress is therefore important for maximizing future crop
yields. The aim of this study was to compare the effects of drought on soybean
(Glycine max) leaves and nodules in order to define phenotypic markers and
changes in cellular redox state that characterize the stress response in
different organs, and to characterize the relationships between leaf and nodule
senescence during drought. METHODS: Leaf and crown nodule metabolite pools were
measured together with leaf and soil water contents, and leaf chlorophyll, total
protein contents and chlorophyll a fluorescence quenching parameters in nodulated
soybeans that were grown under either well-watered conditions or deprived of
water for up to 21 d. KEY RESULTS: Ureides, ascorbate, protein, chlorophyll and
the ratios of variable chlorophyll a fluorescence (Fv') to maximal chlorophyll a
fluorescence (Fm') fell to levels below detection in the oldest leaves after 21 d
of drought. While these drought-induced responses were not observed in the
youngest leaf ranks, the Fv'/Fm' ratios, pyridine nucleotide levels and the
reduction state of the ascorbate pool were lower in all leaf ranks after 21 d of
drought. In contrast to leaves, total nodule protein, pyridine nucleotides,
ureides, ascorbate and glutathione contents increased as a result of the drought
treatment. However, the nodule ascorbate pool was significantly less reduced as a
result of drought. Higher levels of transcripts encoding two peroxiredoxins were
detected in nodules exposed to drought stress but senescence-associated
transcripts and other mRNAs encoding redox-related proteins were similar under
both conditions. CONCLUSIONS: While the physiological impact of the drought was
perceived throughout the shoot, stress-induced senescence occurred only in the
oldest leaf ranks. At this stage, a number of drought-induced changes in nodule
metabolites were observed but no metabolite or transcript markers of senescence
could be detected. It is concluded that stress-induced senescence in the lowest
leaf ranks precedes nodule senescence, suggesting that leaves of low
photosynthetic capacity are sacrificed in favour of nodule nitrogen metabolism.
PMID- 25851141
TI - Red:far-red light conditions affect the emission of volatile organic compounds
from barley (Hordeum vulgare), leading to altered biomass allocation in
neighbouring plants.
AB - BACKGROUND AND AIMS: Volatile organic compounds (VOCs) play various roles in
plant-plant interactions, and constitutively produced VOCs might act as a cue to
sense neighbouring plants. Previous studies have shown that VOCs emitted from the
barley (Hordeum vulgare) cultivar 'Alva' cause changes in biomass allocation in
plants of the cultivar 'Kara'. Other studies have shown that shading and the low
red:far-red (R:FR) conditions that prevail at high plant densities can reduce the
quantity and alter the composition of the VOCs emitted by Arabidopsis thaliana,
but whether this affects plant-plant signalling remains unknown. This study
therefore examines the effects of far-red light enrichment on VOC emissions and
plant-plant signalling between 'Alva' and 'Kara'. METHODS: The proximity of
neighbouring plants was mimicked by supplemental far-red light treatment of VOC
emitter plants of barley grown in growth chambers. Volatiles emitted by 'Alva'
under control and far-red light-enriched conditions were analysed using gas
chromatography-mass spectrometry (GC-MS). 'Kara' plants were exposed to the VOC
blend emitted by the 'Alva' plants that were subjected to either of the light
treatments. Dry matter partitioning, leaf area, stem and total root length were
determined for 'Kara' plants exposed to 'Alva' VOCs, and also for 'Alva' plants
exposed to either control or far-red-enriched light treatments. KEY RESULTS:
Total VOC emissions by 'Alva' were reduced under low R:FR conditions compared
with control light conditions, although individual volatile compounds were found
to be either suppressed, induced or not affected by R:FR. The altered composition
of the VOC blend emitted by 'Alva' plants exposed to low R:FR was found to affect
carbon allocation in receiver plants of 'Kara'. CONCLUSIONS: The results indicate
that changes in R:FR light conditions influence the emissions of VOCs in barley,
and that these altered emissions affect VOC-mediated plant-plant interactions.
PMID- 25851142
TI - A climate change context for the decline of a foundation tree species in south
western Australia: insights from phylogeography and species distribution
modelling.
AB - BACKGROUND AND AIMS: A worldwide increase in tree decline and mortality has been
linked to climate change and, where these represent foundation species, this can
have important implications for ecosystem functions. This study tests a combined
approach of phylogeographic analysis and species distribution modelling to
provide a climate change context for an observed decline in crown health and an
increase in mortality in Eucalyptus wandoo, an endemic tree of south-western
Australia. METHODS: Phylogeographic analyses were undertaken using restriction
fragment length polymorphism analysis of chloroplast DNA in 26 populations across
the species distribution. Parsimony analysis of haplotype relationships was
conducted, a haplotype network was prepared, and haplotype and nucleotide
diversity were calculated. Species distribution modelling was undertaken using
Maxent models based on extant species occurrences and projected to climate models
of the last glacial maximum (LGM). KEY RESULTS: A structured pattern of diversity
was identified, with the presence of two groups that followed a climatic gradient
from mesic to semi-arid regions. Most populations were represented by a single
haplotype, but many haplotypes were shared among populations, with some having
widespread distributions. A putative refugial area with high haplotype diversity
was identified at the centre of the species distribution. Species distribution
modelling showed high climatic suitability at the LGM and high climatic stability
in the central region where higher genetic diversity was found, and low
suitability elsewhere, consistent with a pattern of range contraction.
CONCLUSIONS: Combination of phylogeography and paleo-distribution modelling can
provide an evolutionary context for climate-driven tree decline, as both can be
used to cross-validate evidence for refugia and contraction under harsh climatic
conditions. This approach identified a central refugial area in the test species
E. wandoo, with more recent expansion into peripheral areas from where it had
contracted at the LGM. This signature of contraction from lower rainfall areas is
consistent with current observations of decline on the semi-arid margin of the
range, and indicates low capacity to tolerate forecast climatic change.
Identification of a paleo-historical context for current tree decline enables
conservation interventions to focus on maintaining genetic diversity, which
provides the evolutionary potential for adaptation to climate change.
PMID- 25851143
TI - Neonatal leukaemia cutis.
AB - Neonatal leukaemia cutis is a significant neoplasm that may represent a cutaneous
manifestation of systemic leukaemia, usually of myeloblastic type. Rarely, it may
be or appear to be limited to skin, in which case it is called neonatal
aleukaemic leukaemia cutis. By definition, it presents within the first 4 weeks
of life and often has a 'blueberry muffin baby' appearance of magenta coloured
nodules affecting almost any area of the skin, usually sparing mucous membranes,
palms and soles. This clinical pattern is more commonly associated with neonatal
infections such rubella and toxoplasmosis, and may be evident with other neonatal
neoplasms such as neuroblastoma. Due to the morbidity associated with
chemotherapy and reported cases of spontaneous remission without systemic
progression in those with neonatal aleukaemic leukaemia cutis without 11q23
translocation, the authors not treating the child with chemotherapy, but to
simply monitor for fading of the violaceous nodules, and watch for possible signs
of systemic leukaemia.
PMID- 25851144
TI - What understanding tendon cell differentiation can teach us about pathological
tendon ossification.
AB - Tendons are the structures that attach muscles to bones and transmit mechanical
forces. Tendon cells are composed of mature tenocytes and a rare population of
tendon stem cells. Both cell types ensure homeostasis and repair of tendon
extracellular matrix to guarantee its specific mechanical properties. Moreover,
tendon cells seem to present a marked potential for trans-differentiation,
predominantly into the chondrocyte and osteoblast lineages. In this review
article, we first present chronic tendon pathologies associated with abnormal
ossification, such as spondyloarthritis and calcifying tendinopathy, and discuss
how tendon cell differentiation and trans-differentiation may participate in
these diseases. We moreover present the factors known to influence tendon cell
differentiation and trans-differentiation, with a particular emphasis on
extracellular environment, mechanical stimulation and several soluble factors
that can tip the balance toward one or another lineage. A better understanding of
the neglected tendon cell biology may be extremely useful to understand the
pathological mechanisms of spondyloarthritis and calcifying tendinopathy.
PMID- 25851145
TI - Evaluation of Vessel Sealing Performance Among Ultrasonic Devices in a Porcine
Model.
AB - BACKGROUND: As new technologies emerge, it is imperative to define which new
devices are most likely to provide a reproducible, effective result for the
patient and surgeon. The purpose of our study was to analyze 3 commercially
available ultrasonic energy devices; the Sonicision (SC), the Harmonic ACE (HA),
and the THUNDERBEAT (TB). MATERIAL AND METHODS: Eight female Yorkshire pigs were
used for data collection and vessel harvest. Three devices were evaluated and
compared with each other with respect to seal failure and cutting speed in vivo.
After vessel harvest, one end of the fragment was sent for histological
evaluation, and the other was used for burst pressure measurement testing in a
blinded fashion. The coagulation and cut levels of all the generators were set up
at a similar and constant level. RESULTS: Eighty-four vessels (47 arteries and 37
veins) were tested. Mean vessel diameter was equal among the groups. Cutting
speed was significantly faster with TB (3.4 +/- 0.7 seconds) than SC or HA (5.8
+/- 2.4 and 6.1 +/- 3.1 seconds; P < .0001). Burst pressure trended higher after
ligation with TB (505.4 +/- 349.4 mm Hg) than SC and HA (435.8 +/- 403.0 and
437.6 +/- 291.3 mm Hg). There were 2 seal failures in the SC group and HA group
and none in the TB group. Histologically, the perpendicular width of tissue seal
with TB (1.250 +/- 0.55 mm) was significantly longer than that of the SC and the
HA (0.772 +/- 0.23 and 0.686 +/- 0.23 mm; P < .0001). CONCLUSIONS: TB has proven
to provide the most rapid and reliable seal. Therefore, TB may be safer and may
decrease time during surgical procedures.
PMID- 25851146
TI - Neurosurgical Assessment of Metrics Including Judgment and Dexterity Using the
Virtual Reality Simulator NeuroTouch (NAJD Metrics).
AB - Advances in computer-based technology has created a significant opportunity for
implementing new training paradigms in neurosurgery focused on improving skill
acquisition, enhancing procedural outcome, and surgical skills assessment.
NeuroTouch is a computer-based virtual reality system that can generate output
data known as metrics from operator performance during simulated brain tumor
resection. These measures of quantitative assessment are used to track and
compare psychomotor performance during simulated operative procedures. Data
output from the NeuroTouch system is recorded in a comma-separated values file.
Data mining from this file and subsequent metrics development requires the use of
sophisticated software and engineering expertise. In this article, we introduce a
system to extract a series of new metrics using the same data file using Excel
software. Based on the data contained in the NeuroTouch comma-separated values
file, 13 novel NeuroTouch metrics were developed and classified. Tier 1 metrics
include blood loss, tumor percentage resected, and total simulated normal brain
volume removed. Tier 2 metrics include total instrument tip path length, maximum
force applied, sum of forces utilized, and average forces utilized by the
simulated ultrasonic aspirator and suction instrument along with pedal activation
frequency of the ultrasonic aspirator. Advanced tier 2 metrics include instrument
tips average separation distance, efficiency index, ultrasonic aspirator path
length index, coordination index, and ultrasonic aspirator bimanual forces ratio.
This system of data extraction provides researchers expedited access for
analyzing the data files available for NeuroTouch platform to assess the multiple
psychomotor and cognitive neurosurgical skills involved in complex surgical
procedures.
PMID- 25851147
TI - Lazare Riviere (1589-1655 AD), the Pioneer Pharmacologist, Anatomist, and
Surgeon, Who Gave the First Modern Description of an Aortic Valve Failure.
PMID- 25851148
TI - Design principles of a conditional futile cycle exploited for regulation.
AB - In this report, we characterize the design principles of futile cycling in
providing rapid adaptation by regulatory proteins that act as environmental
sensors. In contrast to the energetically wasteful futile cycles that are avoided
in metabolic pathways, here we describe a conditional futile cycle exploited for
a regulatory benefit. The FNR (fumarate and nitrate reduction) cycle in
Escherichia coli operates under two regimes - a strictly futile cycle in the
presence of O2 and as a pathway under anoxic conditions. The computational
results presented here use FNR as a model system and provide evidence that
cycling of this transcription factor and its labile sensory cofactor between
active and inactive states affords rapid signaling and adaptation. We modify a
previously developed mechanistic model to examine a family of FNR models each
with different cycling speeds but mathematically constrained to be otherwise
equivalent, and we identify a trade-off between energy expenditure and response
time that can be tuned by evolution to optimize cycling rate of the FNR system
for a particular ecological context. Simulations mimicking experiments with
proposed double mutant strains offer suggestions for experimentally testing our
predictions and identifying potential fitness effects. Our approach provides a
computational framework for analyzing other conditional futile cycles, which when
placed in their larger biological context may be found to confer advantages to
the organism.
PMID- 25851149
TI - Urinary iodine level and its determinants in pregnant women of Shanghai, China.
AB - It is known that iodine deficiency during pregnancy can interfere with normal
fetal growth and development. However, iodine levels of pregnant women in
Shanghai, China, and factors that could influence its levels remain unclear. A
total of 916 pregnant women were selected from the Maternal and Child Care
Service Centre of Minhang District in Shanghai. Morning urinary iodine (UI) and
iodine content of salt from the participants' home were measured, and UI
concentration was adjusted by creatinine concentrations. Serum tri-iodothyronine,
thyroxin, free tri-iodothyronine, free thyroxine and thyroid-stimulating hormone
were tested in the second trimester of pregnancy by time-resolved
fluoroimmunoassay. The median levels of UI in pregnant women were 156.3, 176.9
and 175.1 MUg/g creatinine in the first, second and third trimesters of
pregnancy, respectively. The prevalence of UI deficiency (UI < 150 MUg/g
creatinine) was 48.3, 34.2 and 36.2% in the three trimesters of pregnancy,
respectively. Factors that significantly influenced the UI levels include the
following: iodine content of household salt; age; occupation; multivitamin
supplement with iodine; seaweed intakes. Furthermore, UI and iodine content of
salt were moderately correlated (r 0.406, P < 0.001). In addition, there was no
significant association between UI and thyroid hormone levels. The present study
showed a high prevalence of UI deficiency in pregnant women in Shanghai,
especially during the first trimester of pregnancy. Both iodine content of
household salt and multivitamin supplement with iodine are the main determinants
of UI levels in Shanghai.
PMID- 25851150
TI - Effects of phosphate limitation on soluble microbial products and microbial
community structure in semi-continuous Synechocystis-based photobioreactors.
AB - All bacteria release organic compounds called soluble microbial products (SMP) as
a part of their normal metabolism. In photobioreactor (PBR) settings, SMP
produced by cyanobacteria represent a major pool of carbon and electrons
available to heterotrophic bacteria. Thus, SMP in PBRs are a major driver for the
growth of heterotrophic bacteria, and understanding the distribution of SMP in
PBRs is an important step toward proper management of PBR microbial communities.
Here, we analyzed the SMP and microbial communities in two Synechocystis sp.
PCC6803-based PBRs. The first PBR (PBRP0) became phosphate limited after several
days of operation, while the second PBR (PBRP+) did not have phosphate
limitation. Heterotrophic bacteria were detected in both PBRs, but PBRP0 had a
much higher proportion of heterotrophic bacteria than PBRP+. Furthermore, PBRP+
had greater biomass production and lower SMP production per unit biomass than
PBRP0. Carbohydrates that were most likely derived from hydrolysis of
extracellular polymeric substances (EPS) dominated the SMP in PBRP0, while
products resulting from cell lysis or decay dominated the SMP in PBRP+. Together,
our data support that maintaining phosphate availability in Synechocystis-based
PBRs is important for managing SMP and, thus, the heterotrophic community.
PMID- 25851151
TI - High arterial ligation and risk of anastomotic leakage in anterior resection for
rectal cancer in patients with increased cardiovascular risk.
AB - AIM: Controversy still exists as to whether division of the inferior mesenteric
artery close to the aorta influences the risk of anastomotic leakage after
anterior resection for rectal cancer. This population-based study was carried out
to evaluate the independent association between high arterial ligation and
anastomotic leakage in patients with increased cardiovascular risk. METHOD: All
2673 cases of registered anterior resection for rectal cancer from 2007 to 2010
were identified from the Swedish Colorectal Cancer Registry and cross-referenced
with the Prescribed Drugs Registry, rendering a cohort of all patients with
increased cardiovascular risk. Operative charts and registered data were reviewed
for 722 patients. The association between high tie and anastomotic leakage, as
quantified by ORs and 95% CIs, was evaluated in a logistic regression model, with
adjustment for confounding, including assessment of interaction. RESULTS:
Symptomatic anastomotic leakage occurred in 12.3% (41/334) of patients in the
high tie group and in 10.6% (41/388) in the low tie group. The use of high tie
was not independently associated with a higher risk of anastomotic leakage (OR =
1.05; 95% CI: 0.61-1.84). In a post-hoc analysis, patients with a history of
manifest cardiovascular disease and American Society of Anesthesiologists (ASA)
score III-IV seemed to be at greater risk (OR = 3.66; 95% CI: 1.04-12.85).
CONCLUSION: In the present population-based, observational setting, high tie was
not independently associated with an increased risk of symptomatic anastomotic
leakage after anterior resection for rectal cancer. However, this conclusion may
not hold for patients with severe cardiovascular disease.
PMID- 25851152
TI - The importance of communicating uncertainties in forecasts: overestimating the
risks from winter storm Juno.
PMID- 25851154
TI - Authors' reply to Wardlaw and Berge.
PMID- 25851156
TI - Adult-type rhabdomyoma of the cervical esophagus.
PMID- 25851155
TI - The change in nasal inflammatory markers after intranasal challenges with
particulate chitin and lipopolysaccharide: a randomized, double-blind, placebo
controlled, crossover study with a positive control.
AB - BACKGROUND: We investigated the effect of chitin on the inflammation and immune
modulation of the nasal mucosa. This compound was compared to placebo and as a
positive control we used lipopolysaccharide (LPS). METHODS: Fourteen healthy
nonsmoking volunteers 22 to 28 years of age were included. All persons underwent
exposure to chitin microparticles (CP) and placebo in a randomized double-blinded
fashion. In a last session we used LPS from Enterobacter agglomerans in a single
blinded fashion. There were 2 weeks between each session. The outcome measures
were Total Nasal Symptom Score (TNSS) and nasal lavage for cytokines and cells at
0, 3, 4, 8 hours. RESULTS: We showed that CP was only weakly inflammatory
compared to LPS. In contrast to the LPS response, we did however show an immune
regulatory effect of CP on enhanced interleukin (IL)-4 and IL-6 responses known
to downregulate T helper 2 (Th2) responses, indicating a potential beneficial
effect of CP for the regulation of the allergic Th2 immune response. CONCLUSION:
This study also shows that CP is well tolerated in healthy volunteers, and that
does not induce significantly more symptoms compared to placebo. In fact there is
a tendency for CP instillation to induce less rhinorrhoea compared to placebo.
PMID- 25851157
TI - Successful extraction of a carelessly impacted bile duct stone using
sphincterotome.
PMID- 25851158
TI - Improvement in the visibility of colorectal polyps by using blue laser imaging
(with video).
AB - BACKGROUND: Fujifilm developed blue laser imaging (BLI) via a laser light source
with a narrow-band light observation function. It has a brighter BLI bright mode
for tumor detection. OBJECTIVE: To investigate whether the BLI bright mode can
improve the visibility of colorectal polyps compared with white light (WL).
DESIGN: We studied 100 colorectal polyps (protruding, 42; flat, 58; size, 2-20
mm) and recorded videos of the polyps by using the BLI bright mode and WL at
Kyoto Prefectural University of Medicine and Fukuoka Chikushi University
Hospital. The videos were evaluated by 4 expert endoscopists and 4 nonexperts.
Each endoscopist evaluated the videos in a randomized order. Each polyp was
assigned a visibility score from 4 (excellent visibility) to 1 (poor visibility).
SETTING: Japanese academic units. MAIN OUTCOME MEASUREMENTS: The visibility
scores in each mode and their relationship to the clinical characteristics were
analyzed. RESULTS: The mean visibility scores of the BLI bright mode were
significantly higher than those of WL for both experts and nonexperts (experts,
3.10 +/- 0.95 vs 2.90 +/- 1.09; P = .00013; nonexperts, 3.04 +/- 0.94 vs 2.78 +/-
1.03; P < .0001). For all nonexperts, the visibility scores of the BLI bright
mode were significantly higher than those of WL; however, these scores were
significantly higher in only 2 experts. For experts, the mean visibility scores
of the BLI bright mode was significantly higher than those of WL for flat polyps,
neoplastic polyps, and polyps located on the left side of the colon and the
rectum. LIMITATIONS: Small sample size and review of videos. CONCLUSIONS: Our
study showed that polyps were more easily visible with the BLI bright mode
compared with WL. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000013770.).
PMID- 25851160
TI - Recurrent acute pancreatitis secondary to Ascaris lumbricoides.
PMID- 25851159
TI - Practice patterns of sedation for colonoscopy.
AB - BACKGROUND: Sedative and analgesic medications have been used routinely for
decades to provide patient comfort, reduce procedure time, and improve
examination quality during colonoscopy. OBJECTIVE: To evaluate trends of sedation
during colonoscopy in the United States. SETTING: Endoscopic data repository of
U.S. gastroenterology practices (Clinical Outcomes Research Initiative, CORI
database from 2000 until 2013). PATIENTS: The study population was made up of
patients undergoing a total of 1,385,436 colonoscopies. INTERVENTIONS:
Colonoscopy without any intervention or with mucosal biopsy, polypectomy, various
means of hemostasis, luminal dilation, stent placement, or ablation. MAIN OUTCOME
MEASUREMENTS: Dose of midazolam, diazepam, fentanyl, meperidine, diphenhydramine,
promethazine, and propofol used for sedation during colonoscopy. RESULTS: During
the past 14 years, midazolam, fentanyl, and propofol have become the most
commonly used sedatives for colonoscopy. Except for benzodiazepines, which were
dosed higher in women than men, equal doses of sedation were given to female and
male patients. White patients were given higher doses than other ethnic groups
undergoing sedation for colonoscopy. Except for histamine-1 receptor antagonists,
all sedative medications were given at lower doses to patients with increasing
age. The dose of sedatives was higher in colonoscopies associated with procedural
interventions or of long duration. LIMITATIONS: Potential for incomplete or
incorrect documentation in the database. CONCLUSION: The findings reflect on
colonoscopy practice in the United States during the last 14 years and provide an
incentive for future research on how sex and ethnicity influence sedation
practices.
PMID- 25851161
TI - Recurrence rates after EMR of large sessile serrated polyps.
AB - BACKGROUND: Little is known regarding the recurrence rate after EMR of large
(>=20 mm) sessile serrated adenoma/polyps (SSA/Ps). OBJECTIVE: To compare the
recurrence rate among SSA/Ps and conventional adenomas in patients referred to a
specialty practice for EMR. DESIGN: Retrospective cohort study. SETTING: Academic
hospital and a satellite surgery center. PATIENTS: A total of 362 consecutive
patients referred for resection of large (>=20 mm) polyps in the colorectum.
INTERVENTIONS: All EMRs were performed with a submucosal contrast agent. All
subjects had a follow-up surveillance examination (inspection and biopsy of the
EMR) at our center. MAIN OUTCOME MEASUREMENTS: Rates of residual polyp at follow
up examination. RESULTS: Residual polyp was identified among 8.7% of SSA/Ps
compared with 11.1% for conventional adenomas (P = .8). LIMITATIONS:
Retrospective design, procedures performed by a single experienced endoscopist,
low number of serrated lesions. CONCLUSIONS: The rate of recurrence after EMR of
SSA/Ps is similar to the rate after EMR of conventional adenomas.
PMID- 25851163
TI - The impact of commissioning for rhinosinusitis in England.
AB - OBJECTIVES: To assess the compliance of clinical commissioning groups (CCGs) in
England with the ENT-UK rhinosinusitis commissioning guide produced in
collaboration with the Royal College of Surgeons England and the National
Institute of Clinical Excellence. We also aimed to assess the ease of
accessibility of data from CCGs. DESIGN: Audit of compliance of English CCGs with
the ENT-UK rhinosinusitis commissioning guide. SETTING: CCGs in England
PARTICIPANTS: A total of 58 of the 221 CCGs in England were included and chosen
because they were the first CCGs authorised by NHS England, or alternately, the
CCGs forecasted to have a deficit in their first year of operation. Their
websites were reviewed; when information was not easily accessible, a freedom of
information request was submitted to the relevant CCG. MAIN OUTCOME MEASURES:
Compliance with commissioning guidelines for rhinosinusitis. RESULTS: Thirteen
percent of CCGs had restrictive referral criteria in place, largely unrelated to
published evidence-based guidance. The routine use of multiple courses of oral
steroids, prescription of antibiotics, CT scanning within primary care, and
delaying referral for a year, prior to referral to a specialist were recommended
against published advice. CONCLUSIONS: Restricting access to surgery may
contribute to poorer outcomes and a decrease in the patient's quality of life.
This is against the NHS constitution and is open to legal challenge. We encourage
all ENT surgeons to review policies of their local CCG and engage with
commissioners to ensure that their patients have evidence-based care.
PMID- 25851162
TI - Survival and clinical outcome after endoscopic duodenal stent placement for
malignant gastric outlet obstruction: comparison of pancreatic cancer and
nonpancreatic cancer.
AB - BACKGROUND: Data on endoscopic stenting of malignant gastric outlet obstruction
(GOO) are based on studies predominantly involving patients with pancreatic
adenocarcinoma. OBJECTIVE: To compare survival and clinical outcome after stent
placement for GOO due to pancreatic cancer compared with nonpancreatic cancer.
DESIGN: Retrospective study. SETTING: Single tertiary hospital. PATIENTS: A total
of 292 patients with malignant GOO. INTERVENTION: Stent placement. MAIN OUTCOME
MEASUREMENTS: Post-stent placement survival and clinical outcome. RESULTS: In 196
patients with pancreatic cancer and 96 with nonpancreatic cancer, median post
stent placement survival was similar (2.7 months in pancreatic cancer vs 2.4
months in nonpancreatic cancer). Overall survival was shorter in patients with
pancreatic cancer (13.7 vs 17.1 months; P = .004). Clinical success rates at 2
months (71% vs 91%) and reintervention rates (30% vs 23%) were comparable. Post
stent placement chemotherapy and the absence of distant metastasis were
associated with better post-stent placement survival in both groups (pancreatic
cancer: chemotherapy vs no chemotherapy, 5.4 vs 1.5 months, P < .0001; metastasis
vs no metastasis, 1.8 vs 4.6, P = .005; nonpancreatic cancer: chemotherapy vs no
chemotherapy, 9.2 vs 1.8, P = .001; metastasis vs no metastasis, 2.1 vs 6.1, P =
.009). LIMITATIONS: Retrospective study. CONCLUSIONS: In this large series of
patients undergoing stent placement for malignant GOO in North America, we
observed no difference in post-stent placement survival despite better overall
survival in patients with nonpancreatic cancer. GOO is a marker for poor survival
in malignancy, regardless of the type. Chemotherapy and the absence of distant
metastasis were associated with better post-stent placement survival in both
groups.
PMID- 25851164
TI - Chronic probable PTSD in police responders in the world trade center health
registry ten to eleven years after 9/11.
AB - BACKGROUND: Police enrolled in the World Trade Center Health Registry (WTCHR)
demonstrated increased probable posttraumatic stress disorder (PTSD) after the
terrorist attack of 9/11/2001. METHODS: Police enrollees without pre-9/11 PTSD
were studied. Probable PTSD was assessed by Posttraumatic Stress Check List
(PCL). Risk factors for chronic, new onset or resolved PTSD were assessed using
multinomial logistic regression. RESULTS: Half of police with probable PTSD in
2003-2007 continued to have probable PTSD in 2011-2012. Women had higher
prevalence of PTSD than men (15.5% vs. 10.3%, P = 0.008). Risk factors for
chronic PTSD included decreased social support, unemployment, 2+ life stressors
in last 12 months, 2+ life-threatening events since 9/11, 2+ injuries during the
9/11 attacks, and unmet mental health needs. CONCLUSION: Police responders to the
WTC attacks continue to bear a high mental health burden. Improved early access
to mental health treatment for police exposed to disasters may be needed.
PMID- 25851165
TI - Heat-related symptoms in sugarcane harvesters.
AB - BACKGROUND: Exposure to heat stress is a documented risk for Central American
sugarcane harvesters. However, little is known about heat-related illness in this
population. METHODS: This study examined the frequency of heat-related health
effects among harvesters (n = 106) exposed to occupational heat stress compared
to non-harvesters (n = 63). Chi-square test and gamma statistic were used to
evaluate differences in self-reported symptoms and trends over heat exposure
categories. RESULTS: Heat and dehydration symptoms (headache, tachycardia, muscle
cramps, fever, nausea, difficulty breathing, dizziness, swelling of hands/feet,
and dysuria) were experienced at least once per week significantly more
frequently among harvesters. Percentages of workers reporting heat and
dehydration symptoms increased in accordance with increasing heat exposure
categories. CONCLUSIONS: A large percentage of harvesters are experiencing heat
illness throughout the harvest demonstrating an urgent need for improved
workplace practices, particularly in light of climate change and the epidemic of
chronic kidney disease prevalent in this population.
PMID- 25851167
TI - Isolation and characterization of bacterial strains with the ability to utilize
high concentrations of levulinic acid, a platform chemical from inedible biomass.
AB - Nineteen levulinic acid (LA)-utilizing bacteria were isolated from environmental
samples. Following examination of the use of 80 g/L LA by some isolated strains,
Brevibacterium epidermidis LA39-2 consumed 62.6 g/L LA following 8 days
incubation. The strain also utilized both 90 and 100 g/L LA, with consumption
ratio of 84.3 and 53.3%, respectively, after 10 days incubation.
PMID- 25851166
TI - Case cluster of pneumoconiosis at a coal slag processing facility.
AB - BACKGROUND: During an inspection by the Occupational Safety and Health
Administration (OSHA) of a small coal slag processing plant with 12 current
workers, four cases of pneumoconiosis were identified among former workers.
METHODS: The OSHA investigation consisted of industrial hygiene sampling, a
review of medical records, and case interviews. RESULTS: Some personal sampling
measurements exceeded the OSHA Permissible Exposure Limit (PEL) for total dust
exposures of 15 mg/m(3), and the measured respirable silica exposure of 0.043
mg/m(3), although below OSHA's current PEL for respirable dust containing silica,
was above the American Conference of Governmental Industrial Hygienists'
Threshold Limit Value (TLV). Chest x-rays for all four workers identified small
opacities consistent with pneumoconiosis. CONCLUSION: This is the first known
report of lung disease in workers processing coal slag and raises concerns for
workers exposed to coal slag dust.
PMID- 25851168
TI - Quantitative 3D-KPFM imaging with simultaneous electrostatic force and force
gradient detection.
AB - Kelvin probe force microscopy (KPFM) is a powerful characterization technique for
imaging local electrochemical and electrostatic potential distributions and has
been applied across a broad range of materials and devices. Proper interpretation
of the local KPFM data can be complicated, however, by convolution of the true
surface potential under the tip with additional contributions due to long range
capacitive coupling between the probe (e.g. cantilever, cone, tip apex) and the
sample under test. In this work, band excitation (BE)-KPFM is used to negate such
effects. In contrast to traditional single frequency KPFM, multifrequency BE-KPFM
is shown to afford dual sensitivity to both the electrostatic force and the force
gradient detection, analogous to simultaneous amplitude modulated and frequency
modulated KPFM imaging. BE-KPFM is demonstrated on a Pt/Au/SiO(x) test structure
and electrostatic force gradient detection is found to lead to an improved
lateral resolution compared to electrostatic force detection. Finally, a 3D-KPFM
imaging technique is developed. Force volume (FV) BE-KPFM allows the tip-sample
distance dependence of the electrostatic interactions (force and force gradient)
to be recorded at each point across the sample surface. As such, FVBE-KPFM
provides a much needed pathway towards complete tip-sample capacitive de
convolution in KPFM measurements and will enable quantitative surface potential
measurements with nanoscale resolution.
PMID- 25851169
TI - Hypoxia down-regulates expression of secretory leukocyte protease inhibitor in
bronchial epithelial cells via TGF-beta1.
AB - BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) is a protein with anti
protease and antimicrobial properties that is constitutively secreted from the
airway epithelium. The importance of maintaining a balance between proteases and
anti-proteases, and robust innate defence mechanisms in the airways, is
exemplified by inflammatory lung conditions such as chronic obstructive pulmonary
disease (COPD) and cystic fibrosis (CF). Both conditions present with a high
protease burden in the airways which leads to tissue destruction. These patients
also have an impaired innate immune system in the lungs with bacterial
colonization and frequent airway infections. Moreover, both diseases are
associated with airway hypoxia due to inflammation and mucus plugs. The aim of
the present study was to investigate the role of hypoxia on SLPI production from
the airway epithelium. METHODS: Primary human bronchial epithelial cells were
grown in sub-immersed cultures or as differentiated epithelium in air liquid
interface cultures. Cells were incubated at 21% O2 (normoxia) or 1% O2 (hypoxia),
and the release of SLPI was analysed with ELISA. RT-PCR was used to study the
expression of SLPI and transforming growth factor beta1 (TGF-beta1). RESULTS:
Hypoxia decreased the constitutive production of SLPI by bronchial epithelial
cells. The multifunctional cytokine TGF-beta1, which is known to affect SLPI
expression, showed increased expression in hypoxic bronchial epithelial cells.
When bronchial epithelial cells were exposed to exogenous TGF-beta1 during
normoxia, the SLPI production was down-regulated. Addition of TGF-beta1
neutralizing antibodies partially restored SLPI production during hypoxia,
showing that TGF-beta1 is an important regulator of SLPI during hypoxic
conditions. CONCLUSIONS: The mechanism described here adds to our knowledge of
the pathogenesis of severe pulmonary diseases associated with hypoxia, e.g. COPD
and CF. The hypoxic down-regulation of SLPI may help explain the protease/anti
protease imbalance associated with these conditions and vulnerability to airway
infections. Furthermore, it provides an interesting target for the treatment and
prevention of exacerbation in these patients.
PMID- 25851170
TI - Right Ventricular Enlargement In Utero: Is It Coarctation?
AB - Antenatal diagnosis of right heart enlargement has a wide spectrum of
differential diagnosis from maternal, placental and fetal causes, and outcomes of
all are not known. Coarctation of the aorta is in the differential diagnosis of
right heart enlargement. In our study, we focused to measure multiple cardiac
dimensions in fetuses with right heart enlargement to identify the fetus with
coarctation of the aorta utilizing echocardiographic measurements. Ten
cardiovascular dimensions were measured from fetal studies between 20- and 34
week gestation, and six were measured on postnatal echocardiograms. Z-scores for
the cardiac dimensions were calculated, and each variable for fetuses and infants
was tested using a two-sample t test between patients with and without
coarctation. We excluded fetuses with TAPVR, Shone complex, interrupted aortic
arch, Ebstein anomaly or HLHS. Of the 31 fetuses with in utero right heart
enlargement, 11 had coarctation postnatally and 20 did not have coarctation. We
compared the fetal and newborn cardiac dimensions between the groups. The mean
fetal carotid-subclavian index (CS Index) was 0.7 mm with coarctation compared
with 1.1 mm without coarctation (p < 0.0001). The mean difference in diameter z
scores for fetal aortic isthmus (p < 0.0001), mitral valve (<0.001) and aortic
valve (p < 0.009) was also significantly different. Similar significant
differences were noted postnatally in the diameters of the cardiac dimensions
between the coarctation and no-coarctation group: CS index (p < 0.0001), aortic
isthmus (p < 0.0002) and aortic valve annulus (p < 0.007). A spectrum of
diagnoses was found postnatally in fetuses with right heart enlargement,
including a normal heart. The likelihood of identifying fetuses with coarctation
of the aorta and planning for postnatal management can be refined by noninvasive
screening measurements. A smaller CS index and smaller diameters of the aortic
isthmus, mitral valve and aortic valve were significantly associated prenatally
(p < 0.05) with coarctation of the aorta versus without coarctation and might be
useful in prenatally diagnosing coarctation of the aorta. Postnatally, these
measurements are reproducible. This is the first study utilizing these specific
measurements to diagnose coarctation prenatally.
PMID- 25851171
TI - Valproate in the treatment of epilepsy in girls and women of childbearing
potential.
AB - This document provides guidance on the use of valproate in girls and women of
childbearing age from a joint Task Force of the Commission on European Affairs of
the International League Against Epilepsy (CEA-ILAE) and the European Academy of
Neurology (EAN), following strengthened warnings from the Coordination Group for
Mutual Recognition and Decentralised Procedures-Human (CMDh) of the European
Medicines Agency (EMA), which highlight the risk of malformations and
developmental problems in infants who are exposed to valproate in the womb. To
produce these recommendations, the Task Force has considered teratogenic risks
associated with use of valproate and treatment alternatives, the importance of
seizure control and of patient and fetal risks with seizures, and the
effectiveness of valproate and treatment alternatives in the treatment of
different epilepsies. The Task Force's recommendations include the following: (1)
Where possible, valproate should be avoided in women of childbearing potential.
(2) The choice of treatment for girls and women of childbearing potential should
be based on a shared decision between clinician and patient, and where
appropriate, the patient's representatives. Discussions should include a careful
risk-benefit assessment of reasonable treatment options for the patient's seizure
or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most
effective treatment, the risks and benefits of valproate and other treatment
alternatives should be discussed. (4) Valproate should not be prescribed as a
first-line treatment for focal epilepsy. (5) Valproate may be offered as a first
line treatment for epilepsy syndromes where it is the most effective treatment,
including idiopathic (genetic) generalized syndromes associated with tonic-clonic
seizures. (6) Valproate may be offered as a first-line treatment in situations
where pregnancy is highly unlikely (e.g., significant intellectual or physical
disability). (7) Women and girls taking valproate require regular follow-up for
ongoing consideration of the most appropriate treatment regimen.
PMID- 25851172
TI - Social cognitive deficits and biases in maltreated adolescents in U.K. out-of
home care: Relation to disinhibited attachment disorder and psychopathology.
AB - Children entering out-of-home (OoH) care have often experienced multiple forms of
maltreatment and are at risk of psychiatric disorder and poor long-term outcome.
Recent evidence shows high rates of disinhibited attachment disorder (DAD) among
maltreated adolescents in U.K. OoH care (Kay & Green, 2013). This study aimed to
further understand the mechanisms of outcome in this group through investigation
of social cognitive functioning. Patterns of theory of mind (ToM) and social
information processing were assessed alongside DAD behavior and psychopathology
in 63 adolescents in U.K. OoH care (mean age = 176 months, SD = 22; 48% male; 89%
White British) and 69 low-risk comparison adolescents (mean age = 171 months, SD
= 17; 46% male; 87% White British). Compared to low risk, OoH adolescents showed
a hostile attribution bias and ToM deficit, but this was confounded by language
ability. ToM was associated with reduced hostile attribution and responding
biases and increased social competence, which was further associated with lower
levels of externalizing psychopathology. There was no association between social
cognition and core features of DAD. Social cognitive deficits and biases may play
a role in the high rates of externalizing psychopathology and relationship
functioning difficulties in maltreated samples. Future research should assess
alternative cognitive mechanisms for DAD.
PMID- 25851174
TI - Bayesian hierarchical regression on clearance rates in the presence of "lag" and
"tail" phases with an application to malaria parasites.
AB - We present a principled technique for estimating the effect of covariates on
malaria parasite clearance rates in the presence of "lag" and "tail" phases
through the use of a Bayesian hierarchical linear model. The hierarchical
approach enables us to appropriately incorporate the uncertainty in both
estimating clearance rates in patients and assessing the potential impact of
covariates on these rates into the posterior intervals generated for the
parameters associated with each covariate. Furthermore, it permits us to
incorporate information about individuals for whom there exists only one
observation time before censoring, which alleviates a systematic bias affecting
inference when these individuals are excluded. We use a changepoint model to
account for both lag and tail phases, and hence base our estimation of the
parasite clearance rate only on observations within the decay phase. The Bayesian
approach allows us to treat the delineation between lag, decay, and tail phases
within an individual's clearance profile as themselves being random variables,
thus taking into account the additional uncertainty of boundaries between phases.
We compare our method to existing methodology used in the antimalarial research
community through a simulation study and show that it possesses desirable
frequentist properties for conducting inference. We use our methodology to
measure the impact of several covariates on Plasmodium falciparum clearance rate
data collected in 2009 and 2010. Though our method was developed with this
application in mind, it can be easily applied to any biological system exhibiting
these hindrances to estimation.
PMID- 25851175
TI - High resolution CT study of the chorda tympani nerve and normal anatomical
variation.
AB - OBJECTIVE: The aim of this study was to define the normal anatomical variation of
the course of the CTN through the mastoid temporal bone on high resolution CT
(HRCT). MATERIALS AND METHODS: Retrospective review of 27 consecutive normal HRCT
bilateral temporal bones (n = 54, 14 males and 13 females, mean age 41 years)
reconstructed at 0.4-mm slice thickness specifically measuring (1) origin of CTN
from the posterior genu of the facial nerve (CNVII) and (2) the lateral-most
position of the CTN from the mastoid segment of CNVII. RESULTS: The mean distance
of the CTN origin from the mastoid segment of CNVII was 11.5 mm (standard
deviation, SD = 3.2, 95% CI 10.7-12.3) with no statistically significant
difference between the left and right side observed (p = 0.08). The most lateral
distance of the CTN from CNVII was a mean of 1.3 mm (SD = 0.6, 95% CI 1.2-1.7),
range 0-2.5 mm and again no statistical significance between contralateral sides
was observed (p = 0.11). These measurements demonstrated an excellent level of
agreement between observers as assessed by intraclass correlation calculation.
CONCLUSIONS: Reproducible measurements demonstrate variability of the CTN in both
its origin from the mastoid segment of CNVII and its lateral-most course. Precise
description of the course of the CTN with HRCT may be useful for planning of
otologic surgery and limiting inadvertent nerve injury.
PMID- 25851173
TI - Poly(ADP-ribose) polymerase-13 and RNA regulation in immunity and cancer.
AB - Post-transcriptional regulation of RNA is an important mechanism for activating
and resolving cellular stress responses. Poly(ADP-ribose) polymerase-13 (PARP13),
also known as ZC3HAV1 and zinc-finger antiviral protein (ZAP), is an RNA-binding
protein that regulates the stability and translation of specific mRNAs, and
modulates the miRNA silencing pathway to globally affect miRNA targets. These
functions of PARP13 are important components of the cellular response to stress.
In addition, the ability of PARP13 to restrict oncogenic viruses and to repress
the prosurvival cytokine receptor tumor necrosis factor (TNF)-related apoptosis
inducing ligand receptor 4 (TRAILR4) suggests that it can be protective against
malignant transformation and cancer development. The relevance of PARP13 to human
health and disease make it a promising therapeutic target.
PMID- 25851176
TI - Vestibular evoked myogenic potentials in pediatric patients with familial
Mediterranean fever.
AB - OBJECTIVES: We aimed to investigate whether the chronic autoinflammatory process
in familial Mediterranean fever (FMF), which affects numerous systems, results in
vestibular dysfunction in pediatric patients being followed up for diagnosis of
FMF using VEMP recordings. METHODS: 30 patients (60 ears) diagnosed with FMF and
20 (40 ears) healthy volunteers were included in the study. Following routine
ear, nose, and throat examination, transient-evoked otoacoustic emissions (TEOAE)
and vestibular-evoked myogenic potential (VEMP) tests were performed. RESULTS: A
total of 30 FMF pediatric patients (13 male, 17 female) and 20 controls (8 male,
12 female) were included in the study. The mean age of FMF patients was 12.13 +/-
2.88 years, while that of the controls was 12.90 +/- 2.80 years. All of the
otoacoustic emission results of the patient and control groups were "pass VEMP
recordings received in both ears of patients with FMF (60 ears) and both ears of
controls (40 ears). There was no statistically significant difference for
latencies or amplitudes for either patients or controls (p > 0.05). CONCLUSION:
In order to research the effect of FMF on vestibular functions, we measured VEMP.
However, we did not detect alterations of VEMP in FMF patients.
PMID- 25851177
TI - Residual lifetime and 10 year absolute risks of osteoporotic fractures in Chinese
men and women.
AB - OBJECTIVE: To determine the residual lifetime and 10 year absolute risks of
osteoporotic fractures in Chinese men and women. METHODS: A validated state
transition microsimulation model was used. Microsimulation and probabilistic
sensitivity analyses were performed to address the uncertainties in the model.
All parameters including fracture incidence rates and mortality rates were
retrieved from published literature. Simulated subjects were run through the
model until they died to estimate the residual lifetime fracture risks. A 10 year
time horizon was used to determine the 10 year fracture risks. We estimated the
risk of only the first osteoporotic fracture during the simulation time horizon.
RESULTS: The residual lifetime and 10 year risks of having the first osteoporotic
(hip, clinical vertebral or wrist) fracture for Chinese women aged 50 years were
40.9% (95% CI: 38.3-44.0%) and 8.2% (95% CI: 6.8-9.3%) respectively. For men, the
residual lifetime and 10 year fracture risks were 8.7% (95% CI: 7.5-9.8%) and
1.2% (95% CI: 0.8-1.7%) respectively. The residual lifetime fracture risks
declined with age, whilst the 10 year fracture risks increased with age until the
short-term mortality risks outstripped the fracture risks. Residual lifetime and
10 year clinical vertebral fracture risks were higher than those of hip and wrist
fractures in both sexes. CONCLUSIONS: More than one third of the Chinese women
and approximately one tenth of the Chinese men aged 50 years are expected to
sustain a major osteoporotic fracture in their remaining lifetimes. Due to
increased fracture risks and a rapidly ageing population, osteoporosis will
present a great challenge to the Chinese healthcare system. LIMITATIONS: While
national data was used wherever possible, regional Chinese hip and clinical
vertebral fracture incidence rates were used, wrist fracture rates were taken
from a Norwegian study and calibrated to the Chinese population. Other fracture
sites like tibia, humerus, ribs and pelvis were not included in the analysis,
thus these risks are likely to be underestimates. Fracture risk factors other
than age and sex were not included in the model. Point estimates were used for
fracture incidence rates, osteoporosis prevalence and mortality rates for the
general population.
PMID- 25851178
TI - Anticonvulsant and Sedative Effects of Eudesmin isolated from Acorus tatarinowii
on mice and rats.
AB - This paper was designed to investigate anticonvulsant and sedative effects of
eudesmin isolated from Acorus tatarinowii. The eudesmin (5, 10, and 20 mg/kg) was
administered intraperitoneally (i.p.). The maximal electroshock test (MES) and
pentylenetertrazole (PTZ)-induced seizures in male mice were used to evaluate
anticonvulsant activities of eudesmin, and sedative effects of eudesmin were
evaluated by pentobarbital sodium-induced sleeping time (PST) and locomotor
activity in mice. Finally, the mechanisms of eudesmin were investigated by
determining contents of glutamic acid (Glu) and gamma-aminobutyric acid (GABA) in
epileptic mice, and expressions of glutamate decarboxylase 65 (GAD65), GABAA ,
Bcl-2, and caspase-3 in the brain of chronic epileptic rats. Results of MES and
PTZ tests revealed that eudesmin possesses significant anticonvulsant effects,
and the PST and locomotor activity tests demonstrated that eudesmin has
significant sedative effects. Furthermore, our study revealed that after
treatment with eudesmin, GABA contents increased, whereas Glu contents decreased,
and ratio of Glu/GABA decreased. Our results also indicated that expressions of
GAD65, GABAA, and Bcl-2 were up-regulated by treating with eudesmin, whereas the
caspase-3 obviously was down-regulated. In conclusion, eudesmin has significant
anticonvulsant and sedative effects, and the mechanism of eudesmin may be related
to up-regulation of GABAA and GAD65 expressions, and anti-apoptosis of neuron the
in brain.
PMID- 25851179
TI - Sevoflurane exposure prevents diaphragmatic oxidative stress during mechanical
ventilation but reduces force and affects protein metabolism even during
spontaneous breathing in a rat model.
AB - BACKGROUND: Ventilator-induced diaphragmatic dysfunction is associated with the
generation of oxidative stress, enhanced proteolysis, autophagy and reduced
protein synthesis in the diaphragm. Sevoflurane is a common operating room
anesthetic and can be used in the intensive care medicine as well. Besides its
anesthetic properties, its use in cardiac ischemia-reperfusion models can
maintain protein synthesis and inhibit generation of reactive oxygen species, if
used at the beginning of heart surgery. This study has been performed on the
hypothesis that sevoflurane might protect against ventilator-induced
diaphragmatic dysfunction by preventing the production of oxidative stress.
METHODS: Four-month-old, male Sprague-Dawley rats sedated with sevoflurane
(minimal alveolar concentration = 1) were either mechanically ventilated (MV) for
12 hours (n = 8) or allowed to breathe spontaneously (SB) for 12 hours (n = 8).
An acutely anesthetized group was used as a control (Con) group (n = 8). After
euthanization, diaphragmatic contractile properties, fiber cross-sectional areas,
proteolysis (calpain-1 and caspase-3), and oxidative stress (lipid peroxidation,
protein oxidation) were examined. After testing for normality, 1-way or 2-way
analysis of variance with the Dunnett post hoc test was used to test for
significance. RESULTS: The diaphragm contractile force was similarly reduced at
all stimulation frequencies in the SB and MV groups compared with controls.
Markers of oxidative stress and fiber cross-sectional areas were unaltered
between Con and SB/MV, respectively. The calcium-dependent proteases (calpain-1
and caspase-3) were enhanced in the MV group. The p-AKT/AKT ratio and p
FoxO1/FoxO1 ratio were significantly and similarly reduced after sevoflurane
exposure in the SB and MV group compared with Con group. CONCLUSIONS: Exposure to
sevoflurane did not induce oxidative stress. It led to reduction in diaphragmatic
force. In the MV group, sevoflurane led to the activation of atrophy signaling
pathways. These findings are of particular importance for clinical utilization in
intensive care units and question its use, especially during the phases of SB.
PMID- 25851180
TI - Gene Transfer of Glutamic Acid Decarboxylase 67 by Herpes Simplex Virus Vectors
Suppresses Neuropathic Pain Induced by Human Immunodeficiency Virus gp120
Combined with ddC in Rats.
AB - BACKGROUND: Human immunodeficiency virus (HIV)-related painful sensory
neuropathies primarily consist of the HIV infection-related distal sensory
polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides
only partial relief of pain in patients with HIV/acquired immune deficiency
syndrome because little is known about the exact neuropathological mechanisms for
HIV-associated neuropathic pain (NP). Hypofunction of gamma-aminobutyric acid
(GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve
injury. In this study, we tested the hypothesis that HIV gp120 combined with
antiretroviral therapy reduces spinal GABAergic inhibitory tone and that
restoration of GABAergic inhibitory tone will reduce HIV-related NP in a rat
model. METHODS: The application of recombinant HIV-1 envelope protein gp120 into
the sciatic nerve plus systemic ddC (one antiretroviral drug) induced mechanical
allodynia. The hind paws of rats were inoculated with replication-defective
herpes simplex virus (HSV) vectors genetically encoding gad1 gene to express
glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes the
decarboxylation of glutamate to GABA. Mechanical threshold was tested using von
Frey filaments before and after treatments with the vectors. The expression of
GAD67 in both the lumbar spinal cord and the L4-5 dorsal root ganglia was
examined using western blots. The expression of mitochondrial superoxide in the
spinal dorsal horn was examined using MitoSox imaging. The immunoreactivity of
spinal GABA, pCREB, and pC/EBPbeta was tested using immunohistochemistry.
RESULTS: In the gp120 with ddC-induced neuropathic pain model, GAD67 expression
mediated by the HSV vector caused an elevation of mechanical threshold that was
apparent on day 3 after vector inoculation. The antiallodynic effect of the
single HSV vector inoculation expressing GAD67 lasted >28 days. The area under
the time-effect curves in the HSV vector expressing GAD67 was increased compared
with that in the control vectors (P = 0.0005). Intrathecal GABA-A/B agonists
elevated mechanical threshold in the pain model. The HSV vectors expressing GAD67
reversed the lowered GABA immunoreactivity in the spinal dorsal horn in the
neuropathic rats. HSV vectors expressing GAD67 in the neuropathic rats reversed
the increased signals of mitochondrial superoxide in the spinal dorsal horn. The
vectors expressing GAD67 reversed the upregulated immunoreactivity expression of
pCREB and pC/EBPbeta in the spinal dorsal horn in rats exhibiting NP.
CONCLUSIONS: Based on our results, we suggest that GAD67 mediated by HSV vectors
acting through the suppression of mitochondrial reactive oxygen species and
transcriptional factors in the spinal cord decreases pain in the HIV-related
neuropathic pain model, providing preclinical evidence for gene therapy
applications in patients with HIV-related pain states.
PMID- 25851182
TI - Hybrid imaging with 99mTc-WBC SPECT/CT to monitor the effect of therapy in
diabetic foot osteomyelitis.
AB - This study sought to assess the utility of monitoring response to treatment of
diabetic foot osteomyelitis (DFO) with Tc-99m WBC-labelled single photon emission
computed tomography (SPECT/CT) imaging. This is a retrospective cohort study of
20 patients with DFO with sequential Tc-99m WBC-labelled SPECT/CT imaging.
Radiologic findings of osteomyelitis were evaluated and imaging results were
correlated with clinical outcomes subtracted from chart review. Successful
treatment of osteomyelitis was defined by wound healing and/or lack of re
admission for bone infection of the same site within 1 year. The sensitivity,
specificity, positive predictive value and negative predictive value of SPECT/CT
to determine osteomyelitis treatment remission were 90%, 56%, 69% and 83%,
respectively. Tc-99m WBC-labelled SPECT/CT imaging may be useful to help
determine treatment outcomes for DFO.
PMID- 25851181
TI - Food preparation methods, drinking water source, and esophageal squamous cell
carcinoma in the high-risk area of Golestan, Northeast Iran.
AB - Cooking practices and water sources have been associated with an increased risk
of cancer, mainly through exposure to carcinogens such as heterocyclic amines,
polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case
control study, carried out between 2003 and 2007 in a high-risk region for
esophageal squamous cell carcinoma (ESCC), we sought to investigate the
association between food preparation and drinking water sources and ESCC.
Information on food preparation methods, sources of drinking water, and dietary
habits was gathered from 300 cases and 571 controls matched individually for age,
sex, and neighborhood using a structured questionnaire and a semiquantitative
food frequency questionnaire. Multivariate conditional logistic regression was
used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for
potential confounders and other known risk factors including socioeconomic status
and smoking. More than 95% of the participants reported eating meat, mostly red
meat. Red meat consumption above the 75th percentile increased the odds of ESCC
by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant
68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying
meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking
unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10
year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our
results suggest roles for red meat intake, drinking water source, and food
preparation methods in ESCC, even after adjusting for a large number of potential
confounders.
PMID- 25851183
TI - The relative importance of the domains of work functioning: evaluations of health
impaired employees, healthy employees, and employers.
AB - OBJECTIVE: To determine the relative importance of central work functioning
domains and propose a method for composite weighted measurement of the concept
"work functioning." METHODS: Health-impaired workers, healthy workers, and
employers (n = 277) weighed work functioning domains by participating in a
discrete choice experiment. A logistic regression model was tested to reveal the
relative importance of the domains. RESULTS: The central domains are significant
indicators of the work functioning of health-impaired workers. The domain with
the highest relative importance is quality of work performance, followed by,
respectively, recovery, quantity of work, and capacity to work. This pattern of
results was observed in all subgroups. CONCLUSIONS: The central domains are
relevant indicators of the work functioning of health-impaired workers.
Researchers should consider the relative importance of the domains and use the
proposed weighting procedure, when measuring work functioning.
PMID- 25851184
TI - Well-being improvement in a midsize employer: changes in well-being,
productivity, health risk, and perceived employer support after implementation of
a well-being improvement strategy.
AB - OBJECTIVE: To evaluate employee well-being change and associated change in
productivity, health risk including biometrics, and workplace support over 2
years after implementation of a well-being improvement strategy. METHODS: This
was an employer case study evaluation of well-being, productivity (presenteeism,
absenteeism, and job performance), health risk, and employer support across three
employee assessment spanning 2 years. Employee well-being was compared with an
independent sample of workers in the community. RESULTS: Well-being and job
performance increased and presenteeism and health risk decreased significantly
over the 2 years. Employee well-being started lower and increased to exceed
community worker averages, approaching significance. Well-being improvement was
associated with higher productivity across all measures. Increases in employer
support for well-being were associated with improved well-being and productivity.
CONCLUSIONS: This employer's well-being strategy, including a culture supporting
well-being, was associated with improved health and productivity.
PMID- 25851185
TI - Assessing work-asthma interaction with Amazon Mechanical Turk.
AB - OBJECTIVES: To illustrate the utility of crowdsourcing for occupational health
surveillance. METHODS: Amazon Mechanical Turk was used to recruit and obtain
information from employed persons with asthma, who answered questions about work
asthma interactions. RESULTS: Data collection from 60 subjects required only a
few hours. Participants spent on average 7 minutes responding to seven questions
(one optional) and used an average of 708 words. Work exacerbation, interference
of asthma with work, and suggested workplace accommodation are frequent (83%
reported at least one interaction). CONCLUSIONS: The full spectrum of work-asthma
interactions should be considered. Modern crowdsourcing methods have considerable
potential as occupational health surveillance tools because of their
effectiveness; efficiency and financial viability are additional important
advantages.
PMID- 25851186
TI - Psychosocial working conditions and sickness absence in a general population: a
cohort study of 21,834 workers in Norway (The HUNT Study).
AB - OBJECTIVE: To examine the associations between psychosocial working conditions
and sickness absence. METHODS: Data for 21,834 employed adults from the Nord
Trondelag Health Study (HUNT) were linked to the sickness benefit register and
sickness absence during 1 year after survey participation was analyzed with
logistic regression. RESULTS: A one unit change on a 0 to 3 self-reported job
demand scale was associated with a fully adjusted 24% and 25% increased odds of
sickness absence in men and women, respectively. A one unit change on a 0 to 3
scale for self-reported support at work was associated with a fully adjusted 13%
and 17% reduced odds of sickness absence in men and women, respectively.
CONCLUSIONS: The results of this study indicate that demands, and to some extent
support, at work might influence sickness absence-also when adjusting for a
detailed categorization of occupations.
PMID- 25851187
TI - Marijuana in the workplace: guidance for occupational health professionals and
employers: Joint Guidance Statement of the American Association of Occupational
Health Nurses and the American College of Occupational and Environmental
Medicine.
PMID- 25851190
TI - Is there an association of circulatory hospitalizations independent of mining
employment in coal-mining and non-coal-mining counties in west virginia?
AB - OBJECTIVE: Exposures associated with coal mining activities, including diesel
fuel exhaust, products used in coal processing, and heavy metals and other forms
of particulate matter, may impact the health of nearby residents. We investigated
the relationships between county-level circulatory hospitalization rates (CHRs)
in coal and non-coal-mining communities of West Virginia, coal production, coal
employment, and sociodemographic factors. METHODS: Direct age-adjusted CHRs were
calculated using West Virginia hospitalizations from 2005 to 2009. Spatial
regressions were conducted to explore associations between CHR and total,
underground, and surface coal production. RESULTS: After adjustment, neither
total, nor surface, nor underground coal production was significantly related to
rate of hospitalization for circulatory disease. CONCLUSIONS: Our findings
underscore the significant role sociodemographic and behavioral factors play in
the health and well-being of coal mining communities.
PMID- 25851191
TI - Biomarkers for lung epithelium injury in occupational hexavalent chromium-exposed
workers.
AB - OBJECTIVE: To evaluate whether Club (Clara) cell protein (CC16) and surfactant
associated protein D (SP-D) can be used as biomarkers for lung injury caused by
chromium exposure. METHODS: The concentrations of chromium in the air (CrA),
chromium in the blood (CrB), lung function, CC16, SP-D, tumor necrosis factor
alpha (TNF-alpha), and interleukin-6 (IL-6) were detected in 91 chromium-exposed
workers and 38 controls. RESULTS: In chromium-exposed group, the levels of CrA,
CrB, SP-D, TNF-alpha, and IL-6 were significantly higher, whereas forced
expiratory volume in one second (FEV1), FEV1/FVC, maximal expiratory flow (MEF),
maximum ventilation volume (MVV), CC16, and CC16/SP-D were lower. Negative
correlations were shown between CC16, SP-D or CC16/SP-D, and CrB or inflammatory
cytokines (TNF-alpha and IL-6). Positive relationships were shown between CC16 or
CC16/SP-D with indicators of lung function. Tobacco smoking and chromium exposure
had synergic effects on lung injury. CONCLUSIONS: CC16, as an immunosuppressive
protein, and CC16/SP-D can be used as sensitive and noninvasive biomarkers for
lung injury. Smoking should be banned in chromium workplaces.
PMID- 25851192
TI - Platelet parameters evaluation in benzene-exposed participants: role of
confounding factors.
PMID- 25851193
TI - Risk factors for mortality in Down syndrome.
AB - BACKGROUND: Down syndrome is a genetic condition that contributes to a
significantly shorter life expectancy compared with the general population. We
investigated the most common comorbidities in a population of acute hospital
patients with Down syndrome and further explored what the most common risk
factors for mortality are within this population. METHOD: From our database of
one million patients admitted to National Health Service (NHS) Trusts in northern
England, we identified 558 people who had Down syndrome. We compared this group
with an age- and gender-matched control group of 5580 people. RESULTS: The most
prevalent comorbid diseases within the Down's population were hypothyroidism
(22.9%) and epilepsy (20.3%). However, the conditions that had the highest
relative risks (RRs) in the Down's population were septal defects and dementia.
Respiratory failure, dementia and pneumonia were the most significantly related
comorbidities to mortality in the Down syndrome population. In the control
population, respiratory failure, dementia and renal failure were the most
significant disease contributors. When these contributors were analysed using
multivariate analysis, heart failure, respiratory failure, pneumonia and epilepsy
were the identified risk factors for in-hospital mortality in the Down syndrome
population. Respiratory failure was the sole risk factor for mortality in the
Down syndrome population [RR = 9.791 (1.6-59.9) P <= 0.05], when compared with
the risk factors for mortality in the control population. CONCLUSIONS: There is
significant medical morbidity in Down syndrome. This morbidity contributes to the
lower life expectancy. Respiratory failure is a risk factor for mortality in Down
syndrome. We need to thoroughly investigate people with Down syndrome to ensure
any treatable illnesses are well managed.
PMID- 25851195
TI - Malaria Control in Amerindian Communities of Venezuela : Strengthening Ecohealth
Practice Throughout Conservation Science and Capability Approach.
AB - Adaptive management and ecohealth frameworks were developed for malaria
elimination in Amerindian riparian communities of Venezuela. These frameworks
were developed as a strategy to capture, organize, and communicate connections
among key factors related to local malaria complex systems. Important causal
relationships between social, economic, and environmental stressors which are
determinant of malaria were identified at different levels and assumptions that
guide interventions are offered, based on available scientific knowledge and
input from stakeholders. Drawing on our experience of action research committed
to the health of Amerindian populations and conservation of areas with
biodiversity value, the authors provide lessons to strengthen the practice of an
ecohealth approach. First, conservation targets were considered as a way to
achieve sustainable human well-being rather than as a consequence of well-being.
Second, the effectiveness and sustainability of technical solutions generally
proposed for malaria control depend largely on individual knowledge, attitudes,
and practices. Hence, it is necessary to look at the real opportunities of
choices that Amerindian people have for attaining a life without malaria, and
therefore pay attention to local capabilities, needs, and freedom to choose. The
ecohealth approach can benefit from the capability approach, and we explain why.
PMID- 25851196
TI - Decline of General Intelligence in Children Exposed to Manganese from Mining
Contamination in Puyango River Basin, Southern Ecuador.
AB - Based on ecosystem approaches to health (Ecohealth), this study sought to
identify neurobehavioral disorders in children exposed to several levels of toxic
metal pollution from gold mining in the Puyango River Basin, Southern Ecuador.
Ninety-three children born or living in the study area participated in the study.
A neurobehavioral test battery consisting of 12 tests assessing various functions
of the nervous system was applied as well as a questionnaire regarding events of
exposure of children's mothers to contaminants during perinatal period. Hair
samples were taken from children to determine manganese concentrations.
Descriptive and inferential statistics were applied in order to examine possible
relationships between exposure events, hair manganese, and neurobehavioral
disorders. Having controlled co-variables such as age and educational level, it
was found that children with elevated levels of hair manganese (over 2 MUg/g) had
poor performance in the test of general intelligence (Raven's Progressive Color
Matrices Scale PCM). The Ecohealth approach helped to identify that children in
the lower Puyango Basin with very elevated levels of manganese in the river water
(970 ug/L) are the ones who have the highest levels of hair manganese and the
worst performance in the intelligence test.
PMID- 25851197
TI - Toward Operational Criteria for Ecosystem Approaches to Health.
PMID- 25851198
TI - Charge transfer in MOH(H2O)(+) (M = Mn, Fe, Co, Ni, Cu, Zn) complexes revealed by
vibrational spectroscopy of mass-selected ions.
AB - Charge transfer between a metal and its ligand is fundamental for the structure
and reactivity of a metal complex as it directly dictates the distribution of
electron density within the complex. To better understand such charge transfer
interactions, we studied the vibrational spectra of mass-selected MOH(H2O)(+) (M
= Mn, Fe, Co, Ni, Cu, or Zn) complexes, acquired using cryogenic ion infrared
predissociation spectroscopy. We find that there is a partial charge transfer
from the hydroxide anion to the metal center for these first-row transition
metals, the extent of which is in the order of Mn < Fe < Co < Ni < Cu > Zn,
dictated by the 2nd ionization energy of the bare metal. This gradual change
across the metal series points to the complexity in the electronic structures of
these transition metal complexes. Interestingly, the hydroxide ligand in these
complexes can serves as a sensitive in situ probe of this charge transfer. Its
vibrational frequency varies by >150 cm(-1) for different metal species, and it
is dependent on the electric field produced by the charged metal center. This
dramatic vibrational Stark shift is further modulated by the charge present on
the hydroxide itself, providing a well-defined relationship between the observed
hydroxide frequency and the effective electric field.
PMID- 25851199
TI - Reperfusion Rates of Pulmonary Arteriovenous Malformations after Coil
Embolization: Evaluation with Time-Resolved MR Angiography or Pulmonary
Angiography.
AB - PURPOSE: To assess reperfusion rates after coil embolization for pulmonary
arteriovenous malformations (PAVMs) using time-resolved magnetic resonance (MR)
angiography or pulmonary angiography. MATERIALS AND METHODS: Patients with PAVMs
who underwent embolization and met the following inclusion criteria were
included: (a) embolization was performed using bare or fibered platinum
microcoils or both, (b) the complete cessation of flow was confirmed by digital
subtraction angiography, and (c) follow-up examinations were conducted with time
resolved MR angiography or pulmonary angiography. Coil embolization was performed
in 16 patients with 24 untreated or reperfused PAVMs. Sac embolization was
performed for 12 untreated PAVMs. Feeding artery embolization was performed as
primary embolization in each of the 12 reperfused PAVMs. Five PAVMs were treated
2 to 4 times because of reperfusion. The study included 32 coil embolizations.
Follow-up images were reviewed, and reperfusion rates were assessed. The
relationships between reperfusion and the location of PAVM, size of PAVM (feeding
artery and venous sac), coils (number and total length), timing of embolization
(primary or repeat embolization), and types of coils used (with or without
fibered coils) were examined. RESULTS: Reperfusion rates at 3, 6, 12, and 24
months were 8%, 27%, 36%, and 49%, respectively, for the 12 untreated PAVMs
(primary embolization) and 50%, 50%, 92%, and 100%, respectively, for the 12
reperfused PAVMs (repeat embolization) (P = .0062). No significant differences
were observed in the other parameters measured. CONCLUSIONS: When evaluated with
time-resolved MR angiography or pulmonary angiography, reperfusion rates after
coil embolization for PAVM were considerably high, particularly with repeat
embolization.
PMID- 25851200
TI - Endovascular management of early lung transplant-related anastomotic pulmonary
artery stenosis.
AB - PURPOSE: To report the safety and short-term efficacy of endovascular
interventions for symptomatic lung transplant-related anastomotic pulmonary
artery stenosis (PAS). MATERIALS AND METHODS: From February 2008 to December
2011, 354 lung transplants were performed. Pulmonary arteriography was performed
in 19 patients (63% men; age, 57 y +/- 21, mean +/- SD; seven double-lung
transplants) because of respiratory decompensation (mean 6.7 mo after
transplant). Seven arteriograms were normal, and 12 showed significant PAS. One
patient (5%) underwent angioplasty alone, and 11 patients (57%) underwent stent
placement. RESULTS: All patients underwent general anesthesia, and femoral access
was used for the intervention. Technical success was 100% in the 12 patients
treated. Symptoms improved in all patients who underwent intervention, with
resolution in 11 of 12 (92%). There were no major or minor complications. Three
patients (16%) had recurrent symptoms after discharge secondary to chronic
rejection or pneumonia. Two patients died as a result of sepsis and multiorgan
failure at 2 days and 14 days, respectively, after undergoing only pulmonary
arteriography. In-stent stenosis occurred in 1 (9%) patient who required
additional stent placement. During a mean follow-up period of 11 months, the
remaining stents were patent, and the patients were asymptomatic. CONCLUSIONS:
Endovascular stent placement provides an alternative to open repair for
transplant-related anastomotic PAS. It has low mortality and morbidity rates, and
it has shown excellent short-term functional and anatomic outcomes.
PMID- 25851201
TI - Unpacking the process of interpretation in evidence-based decision making.
PMID- 25851202
TI - Factors Influencing Early Detection of Oral Cancer by Primary Health-Care
Professionals.
AB - The purposes of this study are to determine early detection practices performed
by primary healthcare professionals, to compare medical and dental sub-groups,
and to identify factors that influence the ability of medical and dental
practitioners to recognize precancerous changes and clinical signs of oral
cancer. A 28-item survey instrument was used to interview a total of 330
Jordanian primary health-care professionals (165 dental and 165 medical). An oral
cancer knowledge scale (0 to 31) was generated from correct responses on oral
cancer general knowledge. An early detection practice scale (0 to 24) was
generated from the reported usage and frequency of procedures in oral cancer
examination. Also, a diagnostic ability scale (0 to 100) was generated from
correct selections of suspicious oral lesions. Only 17.8 % of the participants
reported that they routinely performed oral cancer screening in practices. Their
oral cancer knowledge scores ranged from 3 to 31 with a mean of 15.6. The early
detection practice scores ranged from 2 to 21 with a mean of 11.6. A significant
positive correlation was found between knowledge scores and early detection
practice scores (r = 0.22; p < 0.001). The diagnostic ability scores ranged from
11.5 to 96 with a mean of 43.6. The diagnostic ability score was significantly
correlated with knowledge scores (r = 0.39; p < 0.001), but not with early
detection practice scores (r = 0.01; p = 0.92). Few significant differences were
found between medical and dental primary care professionals. Continuous education
courses on early diagnosis of oral cancer and oral mucosal lesions are needed for
primary health-care professionals.
PMID- 25851204
TI - Selecting danger signals: dissociable roles of nucleus accumbens shell and core
glutamate in predictive fear learning.
AB - Conditioned stimuli (CSs) vary in their reliability as predictors of danger.
Animals must therefore select among CSs those that are appropriate to enter into
an association with the aversive unconditioned stimulus (US). The actions of
prediction error instruct this stimulus selection so that when prediction error
is large, attention to the CS is maintained and learning occurs but when
prediction is small attention to the CS is withdrawn and learning is prevented.
Here we studied the role of glutamate acting at rat nucleus accumbens shell
(AcbSh) and core (AcbC) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
(AMPA) receptors in this selection of danger signals. Using associative blocking
and unblocking designs in rats, we show that antagonizing AcbSh AMPA receptors
via infusions of 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2,3-dione
(NBQX; 0.5 MUg) prevents the unblocking of fear learning, whereas antagonizing
AcbC AMPA receptors via infusions of NBQX (0.5 MUg) prevents both the blocking
and unblocking of fear learning. These results identify dissociable but
complementary roles for AcbSh and AcbC glutamate acting at AMPA receptors in
selecting danger signals: AcbSh AMPA receptors upregulate attention and learning
to CSs that signal surprising USs, whereas AcbC AMPA receptors encode the
predicted outcome of each trial.
PMID- 25851203
TI - Factors Influencing Chemotherapy Goal Perception in Newly Diagnosed Cancer
Patients.
AB - Cancer patients who start receiving chemotherapy have difficulty in understanding
the state of their disease, the prognosis, and the purpose of treatment. We used
a survey to evaluate the extent of perception of chemotherapy goal among cancer
patients. Two hundred sixteen cancer patients who received chemotherapy for the
first time participated in the study. The presence of depression and anxiety was
assessed using the "Hospital Anxiety and Depression Scale" (HAD). The consistency
between the patients' perception of the chemotherapy goal and the physician's
perception was described as "right," and the inconsistency was described as
"wrong." Among the patients who participated in the survey, 53.2 % (n = 115) were
receiving adjuvant treatment and 46.8 % (n = 101) were receiving palliative
treatment for metastatic disease. The rate of right and wrong perception of the
chemotherapy goal was 51.9 % (n = 108) and 32.2 % (n = 67), respectively, and the
rate of confused patients was 18.9 % (n = 41). The level of education was shown
to be the only parameter involved in accurate perception of the treatment purpose
(hazard ratio (HR) = 0.444, p = 0.025, 95 % confidence interval (CI) 0.219
0.903). In this study, there was a 51.9 % consistency between the physician's
perception and that of the patient regarding the purpose of treatment. We
demonstrated that the level of education was the unique factor in accurate
perception of chemotherapy goal among cancer patients.
PMID- 25851206
TI - Vascular pathology comes of age: Views and reviews in vascular medicine and
biology.
PMID- 25851205
TI - Skeletal muscle mass and quality: evolution of modern measurement concepts in the
context of sarcopenia.
AB - The first reports of accurate skeletal muscle mass measurement in human subjects
appeared at about the same time as introduction of the sarcopenia concept in the
late 1980s. Since then these methods, computed tomography and MRI, have been used
to gain insights into older (i.e. anthropometry and urinary markers) and more
recently developed and refined methods (ultrasound, bioimpedance analysis and
dual-energy X-ray absorptiometry) of quantifying regional and total body skeletal
muscle mass. The objective of this review is to describe the evolution of these
methods and their continued development in the context of sarcopenia evaluation
and treatment. Advances in these technologies are described with a focus on
additional quantifiable measures that relate to muscle composition and 'quality'.
The integration of these collective evaluations with strength and physical
performance indices is highlighted with linkages to evaluation of sarcopenia and
the spectrum of related disorders such as sarcopenic obesity, cachexia and
frailty. Our findings show that currently available methods and those in
development are capable of non-invasively extending measures from solely 'mass'
to quality evaluations that promise to close the gaps now recognised between
skeletal muscle mass and muscle function, morbidity and mortality. As the largest
tissue compartment in most adults, skeletal muscle mass and aspects of muscle
composition can now be evaluated by a wide array of technologies that provide
important new research and clinical opportunities aligned with the growing
interest in the spectrum of conditions associated with sarcopenia.
PMID- 25851207
TI - Quantitative analysis of inflammatory cells in aortic atherosclerosis of young
adults.
AB - Cellular analysis of aortic atherosclerotic lesions has been pursued extensively
in recent years, although most of these investigations have involved the
detection of inflammatory cells in chronically diseased tissue or artificially
induced atherosclerosis in an animal model. Few studies have attempted to
quantify accurately, using computer analysis systems, the degree of cellular
infiltration in a statistically significant number of samples, in tissue from
young adults. In this study, segments of human aortae were collected at autopsy
from 29 individuals ranging in age from 15 to 35 years. The tissue was embedded
in paraffin and stained using routine histological and automated
immunohistochemical staining techniques. The sections were evaluated using
advanced image analysis techniques to investigate the differences in cellular
composition and cell activation between the dorsal and ventral aspects of the
human aorta and to correlate these findings to the age of the subjects. These
regions have been previously shown to have a high (dorsal) and low (ventral)
probability of developing sudanophilic lesions. Our data demonstrated that
statistically different cell populations exist in the dorsal and ventral regions
of each vessel. The dorsal aspect (i.e., high-probability region) had a greater
number of HAM56(+) (36.9% increase,p = 0.0002) and HLA-DRalpha(+) cells (44.2%
increase,p = 0.0035) than did the ventral surface (i.e., low-probability region),
although there were no significant differences in the number of CD43(+)
lymphocytes. When grouped according to age, results showed significant increases
in the dorsal region when considering HAM56(+) and HLA-DRalpha(+) cells (p = 0033
and 0.046, respectively). Morphologically, a greater number of foam cell
aggregates were found to occur in the dorsal region of the vessel than in the
ventral portion. Our results indicate that the microarchitecture and cellular
composition of the dorsal and ventral aorta are significantly different, with
these variations becoming more marked with age.
PMID- 25851208
TI - Covert congenital cardiovascular malformations discovered in an autopsy series of
nearly 5,000 cases.
AB - The objective of this study was to assess the prevalence of covert congenital
cardiac malformations. A retrospective analysis was made of a personal series of
4,953 consecutive postmortem examinations performed over 35 years (1946-1980) in
a mixed urban and rural region of North Lincolnshire, England. The subjects were
4,210 adults and 743 children (under the age of 16 years). There were 1,635
hospital cases and 3,318 coroner's cases; of the latter, 2,651 were instances of
sudden and unexpected death. Four adults and 99 children with known or suspected
congenital heart disease were excluded from the analysis. Of the remaining 4,850
cases, 25 had benign covert cardiovascular malformation (0.52%), and in
approximately 54 more a covert malformation was considered to have been a
possible contributor to death. This latter group consisted of 44 cases of
bifoliate calcified aortic valves, 6 cases of cardiomyopathy, and 4 miscellaneous
cases. As sudden deaths were grossly over-represented in the series, an
approximate correction factor reduced the prevalence of this group to 0.16%,
giving a prevalence of 0.68% for all covert cases. According to these data, the
true prevalence of congenital cardiac malformations is probably about twice that
of the generally accepted level in live births. The implications for
epidemiological studies pertinent to the etiology of congenital heart disease are
indicated.
PMID- 25851209
TI - Nonpredictive value of fibrosis in dilated cardiomyopathy treated with
metoprolol.
AB - Therapy with beta-adrenergic blocking agents has been advocated as a potential
useful approach in heart failure. Recent studies suggest that histologic
parameters may be helpful in assessing the effectiveness of beta-blocker
treatment in dilated cardiomyopathy (DCM). In order to predict the response to
beta-blockers in DCM, fibrous tissue was evaluated at endomyocardial biopsy (EMB)
in 45 patients (pts) with a mean left ventricular ejection fraction of 0.28 +/-
0.07, who were successively long-term treated with metoprolol (M) (mean dosage
138 +/-26 mg/die). EMB was performed from left (n = 32) or right (n = 13)
ventricle by means of a King's bioptome or the Cordis adaptation of this
instrument. Quantification of fibrous tissue was performed at 9 * magnification
and with a computerized morphometric system. Qualitative evaluation at light
microscopy distinguished four types of fibrosis: pericellular, perivascular,
focal, and endocardial. Volume fraction of fibrous tissue ranged from 1.3 to
35.5% (mean 12.1 +/- 9.3%) and was not significantly correlated with any clinical
variable considered. After 24 +/- 12 months of treatment, 25 pts were considered
improved (group A), whereas the remaining 20 pts were considered not improved
(group B), according to criteria based on ejection fraction, left ventricular end
diastolic diameter, filling pattern at Doppler-Echocardiography, cardiothoracic
ratio, NYHA functional class, and exercise duration at ergometric test. Volume
fraction of fibrous tissue did not differ significantly between the two groups
(group A = 12.1 +/- 9.1%; group B = 11.3 +/- 9.6%;p = NS). Dominant pericellular
type of fibrosis was equally distributed between the two groups (group A = 9 25
pts, 36%; group B = 10 20 pts, 50%), whereas a perivascular and/or focal
replacement fibrosis was more frequent in group A (group A = 10 20 pts, 50%;
group B = 2 20 pts, 10%; p = .05, OR 5.55 at univariate analysis). At
multivariate analysis mean aortic blood pressure was the only variable
discriminating the two groups; the type of fibrosis, although not statistically
significant, maintained a high value of odds-ratio (5.23). In conclusion, extent
of total fibrosis assessed by EMB may range widely in patients with DCM, is not
correlated with the most important clinical variables, and is not predictive of
long-term response to beta-blocker treatment. Otherwise, prevalent perivascular
and/or focal replacement fibrosis could be associated with a higher probability
of improvement after long-term beta-blocker treatment.
PMID- 25851210
TI - Myocardial vacuolization, a marker of ischemic injury, in surveillance cardiac
biopsies posttransplant: Correlations with morphologic vascular disease and
endothelial dysfunction.
AB - Allograft vasculopathy (AV) causes intimal thickening with progressive luminal
obstruction, endothelial dysfunction, and abnormal vasomotion. Subendocardial
vacuolization indicating ongoing ischemia was observed at autopsy in transplanted
hearts with severe AV. Whether myocyte vacuolization can be observed with lesser
degrees of AV in cardia transplant patients has not been reported. Thirty-nine
cardiac transplant patients without flow-limiting disease in large epicardial
arteries underwent invasive assessment of AV. Eight to 10 segments of the left
anterior descending artery were analyzed by intracoronary ultrasound, and an
average intimal index was calculated. Endothelial response to acetylcholine was
assessed with serial quantitative angiography. Endomyocardial biopsies taken 5 to
7 days prior to the invasive studies were histopathologically reviewed for the
presence of small intramyocardial arteries and myocyte vacuolization. Myocyte
vacuolization was evident in biopsies from 20 patients (51%). Intramyocardial
arteries were observed in 30 cases (76%); 14 had abnormal arteries. All patients
had some degree of intimal thickening by intracoronary ultrasound, and 7 (17 %)
had severely abnormal average intimal index (>0.2). Endothelial dysfunction was
present in 23 patients (58%). Vacuolization failed to show an association with
abnormal small artery histology or large epicardial artery ultrasound disease.
However, a significant association between vacuolization and endothelial
dysfunction was observed (p = 0.05). Myocyte vacuolization, possibly indicating
ischemic injury, is common in biopsies from cardiac transplant patients and is
associated with abnormal acetylcholine response in large epicardial arteries. We
speculate that myocyte vacuolization may be caused at least in part by impaired
coronary flow associated with endothelial dysfunction.
PMID- 25851211
TI - Cardiomyopathy in rats with Walker 256 tumor: The potential role of microvascular
disease in its genesis.
AB - Considering that diffuse abnormalities of myocardial microcirculation with
transient ischemia have been suggested to play a role in the genesis of
myocytolytic necrosis, characteristic lesion of dilated or congestive
cardiomyopathies, and the bloodstream is the most common pathway for
dissemination of cancer cells, which gain access to the microcirculation, the
present study was undertaken to search for morphologic and electrocardiographic
evidence of myocardial damage associated with microcirculatory disease in rats
experimentally inoculated with the Walker 256 tumor. Young albino rats inoculated
intramuscularly with the Walker 256 tumor developed a cardiomyopathy
characterized by diffuse small foci of myocytolytic necrosis, decreased thickness
of the mean left midventricular wall associated with reduced size of the minor
diameter of myocytes, and electrocardiographic abnormalities reflecting the
myocardial damage, correlated with the presence of a microvascular disease,
characterized by intramyocardial microvessels (less than 50 MUm in diameter)
partially or totally occluded because of entrapment of tumor cells and fibrin
platelet/tumor cell-cellular debris thrombi. The occlusive or subocclusive small
vessel lesions preceded the development of the myocytolytic necrosis, suggesting
that the microvascular disease would play an important role in the process of
focal micronecrosis and consequent electrocardiographic changes. However, it must
be taken into account that the tumor thromboemboli can generate related factors
that could promote cell injury and cell death. In conclusion, the hematogenic
dissemination of Walker 256 cells promotes the development of an experimental
cardiomyopathy attributable, at least in part, to microvascular obliterative
changes in the myocardium.
PMID- 25851212
TI - Persistence of spongy myocardium with embryonic blood supply in an adult.
AB - Gross presence of the embryonic pattern of myoarchitecture and of a sinusoid
blood supply was found in the apical part of the left ventricle in a man who had
been diagnosed with nonobstructive hypertrophic cardiomyopathy during life and
who died suddenly at age 21 years. This is a first description of this finding in
an adult with an otherwise normal heart and coronary arteries. The features of
the cardiac lesions provide support for the current embryological views on
ontogenesis of human myocardial structure and blood supply.
PMID- 25851213
TI - Value of the endomyocardial biopsy in the diagnosis of toxoplasmosis after heart
transplantation.
PMID- 25851215
TI - Comment on 'Comparative survival of commercial probiotic formulations: tests in
biorelevant gastric fluids and real-time measurements using microcalorimetry'.
PMID- 25851214
TI - Hsp90 regulates the dynamics of its cochaperone Sti1 and the transfer of Hsp70
between modules.
AB - The cochaperone Sti1/Hop physically links Hsp70 and Hsp90. The protein exhibits
one binding site for Hsp90 (TPR2A) and two binding sites for Hsp70 (TPR1 and
TPR2B). How these sites are used remained enigmatic. Here we show that Sti1 is a
dynamic, elongated protein that consists of a flexible N-terminal module, a long
linker and a rigid C-terminal module. Binding of Hsp90 and Hsp70 regulates the
Sti1 conformation with Hsp90 binding determining with which site Hsp70 interacts.
Without Hsp90, Sti1 is more compact and TPR2B is the high-affinity interaction
site for Hsp70. In the presence of Hsp90, Hsp70 shifts its preference. The linker
connecting the two modules is crucial for the interaction with Hsp70 and for
client activation in vivo. Our results suggest that the interaction of Hsp70 with
Sti1 is tightly regulated by Hsp90 to assure transfer of Hsp70 between the
modules, as a prerequisite for the efficient client handover.
PMID- 25851216
TI - Management of chronic spontaneous urticaria in the elderly.
AB - The guidelines for the management of urticaria in adults and children have been
revised and updated recently. However, there are few data in the literature
concerning several aspects of this disease in the elderly (e.g., epidemiology,
etiopathogenesis, clinical aspects, association with co-morbidities, efficacy and
safety profiles of treatments, and management strategies). This is an obvious
deficiency in the data, as this disease causes a deterioration in quality of
life, affecting the quality of sleep, everyday life habits and activities, and
inducing severe disability. Chronic spontaneous urticaria (CSU) can also be
associated with internal, infectious, autoimmune, or neoplastic diseases. It is
therefore necessary to pay particular attention to these clinical issues through
appropriate clinical examinations. At the same time, the specific features of
medications used to treat CSU in the elderly should be carefully evaluated, as
its pharmacological treatment raises a number of problems related both to the
clinical condition of the patient and to concomitant diseases, as well as to the
polypharmacotherapy, which is common in older subjects and may cause safety
problems because of the drug interactions. Non-sedating new-generation
antihistamines are the mainstay treatment of CSU for the elderly. The efficacy
and safety of alternative treatment options have not been assessed in the
geriatric population with CSU; corticosteroids and cyclosporine (ciclosporin)
should be used by this population with extreme caution. Similarly, there are no
data regarding the actual safety profile of the new-generation antihistamines at
higher doses than those recommended in elderly patients.
PMID- 25851218
TI - Mercury levels in common (Actitis hypoleucos) and green (Tringa ochropus)
sandpipers from west-central Iran.
AB - Mercury concentrations were examined in the liver, kidneys, and tail and breast
feathers of common and green sandpipers from Zayanderud Dam in west-central Iran.
The aim was to provide indirect information about habitat contamination. Tail
feathers of both species had higher mercury levels compared to other tissues.
Moreover, tissues of common sandpipers had significantly higher mercury
concentrations compared to tissues of green sandpipers. Male specimens of both
species had higher values of mercury compared to females. The pattern of larger
body size-higher mercury body burden was not completely true in the current
study. Smaller and shorter common sandpipers had higher mercury concentrations
compared to taller and heavier green sandpipers. At the intraspecific level, body
weight was positively correlated with mercury concentrations in tissues of common
sandpipers. Based on the data presented here, it appears that these sandpipers,
especially common sandpipers, are at potential risk from the toxic effects of
mercury.
PMID- 25851219
TI - Cardiac fibroblasts form and function.
AB - The formation and structure of the extracellular matrix (ECM) that makes up the
cardiac interstitum is well known yet the underlying mechanisms that regulate the
interstitum are poorly known. This review focuses on the role of the cardiac
fibroblast in the formation and regulation of the ECM components during cardiac
development and in response to physiological and pathological stimulation. The
role of ECM receptors (integrins), cellular phenotype, and chemical and
mechanical signaling by cardiac fibroblasts are discussed.
PMID- 25851217
TI - Respiratory syncytial virus infection in older adults: an under-recognized
problem.
AB - Human respiratory syncytial virus (RSV) is an enveloped, single-stranded,
negative-sense RNA virus and member of the Paramyxoviridae family of the genus
Pneumovirus that was first reported as a major pathogen in pediatric populations.
However, since its discovery, RSV has not infrequently been detected in adults.
Reinfection occurs throughout life, with more severe disease occurring in older
adults, immunocompromised patients, and those with underlying cardiopulmonary
disease. Initially described as the cause of nursing home outbreaks of
respiratory disease, there is a now significant body of literature describing the
clinical importance of RSV in older adults in a multitude of settings including
long-term care, adult daycares, and in community-dwelling adults. Moreover,
recent reports from China and other countries emphasize that RSV is a global
pathogen that will become increasingly important in developed nations with aging
populations. Annual attack rates in the USA range from 2 to 10% in community
dwelling older adults and 5-10% in older adults living in congregate settings.
Population-based calculations of the proportion of acute respiratory illnesses
attributable to RSV estimate that 11,000 elderly persons die annually in the USA
of illnesses related to RSV infection. Clinical manifestations of RSV infections
are similar to that of other viral respiratory pathogens and include cough, nasal
congestion, rhinorrhea, sore throat, and dyspnea. Lower respiratory tract disease
is common and may result in respiratory failure (8-13%) or death (2-5%). Recent
advances in molecular diagnostics have made it possible to rapidly identify RSV
infection using nucleic acid amplification tests, although clinicians will need
to suspect the diagnosis when viral activity is high. At the present time,
treatment is supportive. Effective antiviral agents for the treatment and
vaccines for prevention of RSV remain a significant unmet medical need in the
older adult population.
PMID- 25851220
TI - Cardiac integrins the ties that bind.
AB - An elaborate series of morphogenetic events must be precisely coordinated during
development to promote the formation of the elaborate three-dimensional structure
of the normal heart. In this study we focus on discussing how interconnections
between the cardiac myocyte and its surrounding environment regulate cardiac form
and function. In vitro experiments from our laboratories provide direct evidence
that cardiac cell shape is regulated by a dynamic interaction between
constituents of the extracellular matrix (ECM) and by specific members of the
integrin family of matrix receptors. Our data indicates that phenotypic
information is stored in the tertiary structure and chemical identity of the ECM.
This information appears to be actively communicated and transduced by the
alpha1beta1 integrin molecule into an intracellular signal that regulates cardiac
cell shape and myofibrillar organization. In this study we have assessed the
phenotypic consequences of suppressing the expression and accumulation of the
alpha1 integrin molecule in aligned cultures of cardiac myocytes. In related
experiments we have examined how the overexpression of alpha2 and alpha5
integrin, integrins normally not present or present at very low copy number on
the cell surface of neonatal cardiac myocytes, affect cardiac protein metabolism.
We also consider how biochemical signals and the mechanical signals mediated by
the integrins may converge on common intracellular signaling pathways in the
heart. Experiments with the whole embryo culture system indicate that angiotensin
II, a peptide that carries information concerning cardiac load, plays a role in
controling cardiac looping and the proliferation of myofibrils during
development.
PMID- 25851221
TI - Regulation of myocardial extracellular matrix components by mechanical and
chemical growth factors.
AB - The cardiac fibroblast is numerically the most abundant cell in the myocardium
and is responsible for the deposition of the extracellular matrix (ECM). The
cardiac ECM is a hierarchical, three-dimensional network in the heart, of which
fibrillar collagens types I and III are the major structural components. Normal
and pathological deposition of fibrillar collagen in the heart appears to rely on
the regulation of ECM components such as fibronectin. Many humoral mediators have
been noted to modulate the function of cardiac fibroblasts. In particular,
angiotensin II and transforming growth factor-beta1 have gained recent attention.
However, growth factors such as endothelin, ANF, and catecholamines among others
are also noted to modify cardiac fibroblast function. Cardiac fibroblasts are
also capable of synthesizing and releasing many of the above mentioned growth
factors which in an autocrine or paracrine fashion may modulate myocardial cell
functions. Cardiac fibroblasts have also been noted to secrete a potent growth
factor that stimulates cardiac myocyte hypertrophy. Recent studies using stretch
apparatuses on cardiac fibroblasts also indicate that these cells respond to such
types of mechanical stimuli. Unfortunately, little is known about human cardiac
fibroblasts since most studies have utilized cells isolated from animal species.
The following study summarizes our current state of knowledge in the field of
mechanical and chemical regulation of myocardial ECM.
PMID- 25851222
TI - Dynamic role of extracellular matrix metalloproteinases in heart failure.
AB - In chronic congestive heart failure, an illness affecting more than 4 million
Americans, there is extensive myocardial extracellular matrix (ECM) remodeling.
Failing human ventricular myocardium contains activated matrix metalloproteinases
(MMPs) which are involved in adverse ECM remodeling. Our studies support the
concept that impaired ECM remodeling and MMP activation are, in part, responsible
for the cardiac structural deformation during heart failure. There is no known
program which has declared its aim the investigation of regulation of fibrosis in
hypertrophy and disruption of ECM in cardiac dilatation and failure. The
development of transgenic technology, and emerging techniques for in vivo gene
transfer, suggest a strategy for improving cardiac function by overexpressing or
down regulation of the ECM components such as MMPs, tissue inhibitor of
metalloproteinases (TIMPs), transforming growth factor beta1 (TGFbeta), decorin,
collagen, and integrins in heart failure.
PMID- 25851223
TI - Myocardial extracellular matrix remodeling with the development of pacing induced
congestive heart failure contributory mechanisms.
AB - The myocardial fibrillar collagens ensure structural integrity of adjoining
myocytes, provide the means by which myocyte shortening is translated into
overall left ventricular (LV) pump function, and have been postulated to be
essential for maintaining alignment of myofibrils within the myocyte through a
collagen-integrin-cytoskeletal-myofibril relation. This laboratory has performed
a series of studies in order to examine the relationship between changes in
myocardial collagen matrix components to LV function and geometry which occurred
in a model of congestive heart failure (CHF) induced by chronic rapid pacing. In
this model of CHF, indices of LV pump function are reduced and accompanied by
significant dilation. LV fibrillar collagen concentration was reduced and salt
extractable collagen, which reflects collagen cross-linking, was increased with
the development of CHF. LV myocyte adhesion capacity to basement membrane
substrates was reduced with pacing CHF. Results from a recently completed series
of studies have demonstrated alterations in the expression and activity of the
collagenases, or matrix metalloproteinases (MMPs) occur during the progression of
CHF. Increased LV myocardial MMP abundance and activity occurred with pacing CHF
and were associated with the development of LV dilation, wall thinning, and pump
dysfunction. These results suggest that changes within the myocardial
extracellular space are a dynamic process and accompany the LV remodeling and
dysfunction which occurs with the development of a CHF process. Future studies
which define the contributory role of MMP synthesis and activation in the LV
remodeling process which occurs in the setting of CHF will likely identify unique
therapeutic modalities to slow the progression of this disease process.
PMID- 25851224
TI - An unusual coronary vein lesion thrombus with calcification.
AB - In this article, a patient with chronic renal failure and probable secondary
hyperparathyroidism is described; calcification of a variety of cardiac and other
structures complicated the latter. Calcification of an occlusive thrombus in the
great cardiac vein and coronary sinus was identified by echocardiography,
although not initially appreciated as such. The echocardiographic similarity of
this lesion to mitral annular calcification is discussed.
PMID- 25851225
TI - Thyroid heterotopia as a rare cause of intrapericardial tumoral mass case report
and review of the literature.
AB - This article describes the interesting discovery of a large tumoral mass formed
of heterotopic thyroid tissue inside the pericardial cavity of an elderly man who
died of unrelated causes. Heterotopic thyroid tissue may be found in many
locations throughout the body. Intracardiac and intrapericardial locations,
however, are exceptionally rare-this is only the second report of
intrapericardial thyroid heterotopia. Such cases may be explained by the
proximity of the developing cardiac structures and the foregut, the latter
containing thyroid primordia during early embryogenesis.
PMID- 25851226
TI - Large epicardial lipoma associated with rupture of the interventricular septum
after an acute myocardial infarct.
AB - We report a case of a large epicardial lipoma associated with an unusual rupture
of an infarcted interventricular septum. The proximity of the attachment of the
lipoma to the rupture site, together with the unusual shape and location of the
rupture, suggest that the lipoma perpetrated the rupture.
PMID- 25851227
TI - Using quality indicators to compare outcomes of permanent cardiac pacemaker
implantation among publicly and privately funded patients.
AB - BACKGROUND: Funding source/insurance status has been associated with disparity in
the management and outcomes of cardiovascular disease, with poorer outcomes among
disadvantaged groups. AIM: Using proposed quality indicators for permanent
pacemaker (PPM) implantation and administrative data, this study aimed to
determine whether quality indicator-based outcomes of PPM implantation were
comparable for publicly and privately funded patients within Australia's two-tier
health system. METHODS: A population-based cohort study of adults implanted with
a PPM between 1995 and 2009 in Western Australia. The association of funding
outcomes derived from linked administrative data was tested in multivariate
logistic regression models. RESULTS: There were 9748 PPMs implanted, 48% being
among privately funded patients. The mean age was 75 years for both public and
private patients. Private patients had better health status (fewer with cardiac
conditions and lower non-cardiac comorbidity scores), were less likely to be an
emergency admission (33% vs 60%, P < 0.001) and more likely to have dual- or
triple-chamber pacing. Mean length of stay was significantly greater for private
patients (4.3 (standard deviation 6.3) vs 5.1 (6.8) days <0.001), related to
longer elective admissions. Crude mortality was lower for private patients in
hospital (0.7 vs 1.3%), 30-day post-procedure (1.3 vs 2.1%) and at 1 year (7.3 vs
9.5%). Emergency admission, comorbidity and other demographic and clinical
factors, not funding source, were significant predictors of these outcomes.
CONCLUSIONS: There was no difference between publicly and privately funded
patients in study outcomes, after adjustment for demographic and clinical
factors. The exception was longer hospital stay for elective PPM among privately
funded patients.
PMID- 25851228
TI - A new insight into ductile fracture of ultrafine-grained Al-Mg alloys.
AB - It is well known that when coarse-grained metals undergo severe plastic
deformation to be transformed into nano-grained metals, their ductility is
reduced. However, there are no ductile fracture criteria developed based on grain
refinement. In this paper, we propose a new relationship between ductile fracture
and grain refinement during deformation, considering factors besides void
nucleation and growth. Ultrafine-grained Al-Mg alloy sheets were fabricated using
different rolling techniques at room and cryogenic temperatures. It is proposed
for the first time that features of the microstructure near the fracture surface
can be used to explain the ductile fracture post necking directly. We found that
as grains are refined to a nano size which approaches the theoretical minimum
achievable value, the material becomes brittle at the shear band zone. This may
explain the tendency for ductile fracture in metals under plastic deformation.
PMID- 25851229
TI - Properties of the Urothelium that Establish the Blood-Urine Barrier and Their
Implications for Drug Delivery.
AB - The primary function of the urinary bladder is to store and periodically release
urine. How the urothelium prevents permeation of water, ions, solutes, and
noxious agents back into the bloodstream and underlying tissues as well as
serving as a sensor and transducer of physiological and nociceptive stimuli is
still not completely understood, and thus its unique functional complexity
remains to be fully elucidated. This article reviews the permeation routes across
urothelium as demonstrated in extensive morphological and electrophysiological
studies on in vivo and in vitro urothelia. We consider the molecular and
morphological structures of urothelium and how they contribute to the
impermeability of the blood-urine barrier. Based on the available data, the
extremely low permeability properties of urothelium can be postulated. This
remarkable impermeability is necessary for the normal functioning of all mammals,
but at the same time represents limitations regarding the uptake of drugs.
Therefore, the current progress to overcome this most resilient barrier in our
body for drug therapy purposes is also summarized in this review.
PMID- 25851230
TI - Towards Understanding the Role of the Na2+-Ca2+ Exchanger Isoform 3.
AB - The Na2+-Ca2+ exchanger (NCX) is critical for Ca2+ homeostasis throughout the
body. Of the three isoforms in the NCX family, NCX1 has been extensively studied,
providing a good basis for understanding the molecular aspects of the NCX family,
including structural resemblances, stoichiometry, and mechanism of exchange.
However, the tissue expression of the third isoform of the family, NCX3, together
with its proposed involvement in the Ca2+ fluxes of the endoplasmic reticulum and
the mitochondria suggests a distinctive role for this isoform. Investigations of
the exchanger revealed the involvement of NCX3 in diverse processes such as bone
formation, TNF-alpha production, slow-twitch muscle contraction, and long-term
potentiation in the hippocampus. Furthermore, the study of its posttranslational
modification, its cleavage by the Ca2+-sensitive protease, calpain, and its
upregulation in numerous stress conditions linked NCX3 to the aberrant Ca2+
influx seen during neuronal excitotoxicity in Alzheimer's disease, brain stroke,
and neuronal injuries. Hence, beyond its role in calcium homeostasis, NCX3 plays
an important role in stress conditions, neuronal excitotoxicity, and metabolism
and is thereby a key element in many cell types. The present review aims to
survey the knowledge on NCX3, focusing on the recent discoveries on its
functional and structural properties, and discusses the implications of NCX3 in
both physiological and pathological conditions.
PMID- 25851231
TI - Hybrid repair of rare type IIIb endoleaks from an abdominal endograft: repeatedly
undetected endoleaks.
AB - We report a rare case of massive type IIIb endoleaks from an abdominal endograft,
which were difficult to diagnose and required hybrid repair (including open
surgery). The patient had previously undergone three catheter interventions for
type Ia and II endoleaks after abdominal endografting. However, the abdominal
aortic aneurysm gradually enlarged and required hybrid treatment (including an
open repair), to successfully perform aneurysmorrhaphy and additional endograft
insertions for the massive type IIIb endoleaks.
PMID- 25851232
TI - High perceived sensitivity to medicines is associated with higher medical care
utilisation, increased symptom reporting and greater information-seeking about
medication.
AB - PURPOSE: The belief that one is especially sensitive to the actions and side
effects of medicines can influence treatment adherence and side-effect reporting.
In this study, we investigated the prevalence of perceived medication sensitivity
in the general population and its relationship to symptom complaints, information
seeking about medications, use of medical care and demographic factors. METHODS:
A nationally representative sample of 1000 New Zealand residents completed the
Perceived Sensitivity to Medicines scale and symptoms experienced during the
previous 7 days. Demographic data and medical visits, medication use and
information seeking about medicines were also collected. RESULTS: Over 20% of the
general population reported being very sensitive to the effects of medication
(20.2%) and that small amounts of medicines can upset their body (25.3%).
Participants who reported high levels of perceived sensitivity to medicines
reported significantly more symptoms (M = 9.54, SE = 0.47) than people with low
(M = 5.04, SE = 0.49) or moderate (M = 5.91, SE = 0.24) levels, ps < .001. This
relationship was strongest in participants who were currently taking prescription
medication. Those with high perceived sensitivity also reported being more likely
to seek information about medicines, and had significantly more general
practitioner visits. CONCLUSIONS: Perceived sensitivity to medicines is common in
the population and associated with important clinical variables including
information seeking, GP visits and symptom reporting. Identifying patients with
higher perceived sensitivity to medicines may improve patient care by providing
the basis for targeted and personalised interventions to reduce side effects and
improve adherence to medications.
PMID- 25851233
TI - Prodromal symptoms associated with acute coronary syndrome acute symptom
presentation.
AB - OBJECTIVE: Prodromal symptoms (PS), indicative of myocardial ischemia, are
frequently unrecognized by individuals prior to an acute coronary syndrome (ACS).
ACSs are the leading cause of death worldwide. This study describes (1) the
prevalence and association of PS with patients' baseline ACS-related acute
symptoms of pain intensity and state anxiety and (2) the relationship of PS to co
morbidity. METHODS: An exploratory sub-analysis was performed. Cross sectional
data identified prodromal predictors of ACS pain intensity (numeric rating scale
0-10 (NRS)) and state anxiety (Speilberger state-trait anxiety personality
inventory (STAI)). ACS patients (n=121) admitted to a community rural emergency
department completed the prodromal symptom screening scale (PS-SS) and reported
baseline cardiac pain intensity, state, and trait anxiety. RESULTS: Increased ACS
pain intensity was associated with PS. Median pain scores were higher by two
points for those with prodromal headache, p=0.006, and anxiety, p=0.017, and one
point higher for those with sleep disturbances, p=0.012. PS were not associated
with state or trait anxiety. Hypertensive individuals were 7.5 times more likely
to experience prodromal fatigue prior to their ACS event. CONCLUSION: Results
extend current knowledge of the predictive value that prodromal headache, sleep
disturbance and anxiety may have on individuals' acute symptom presentation. A
prospective, prognostic study is required in order to determine whether PS are
predictive of adverse cardiac events and if PS are a stronger predictor of ACS
acute symptom presentation, compared with typical ACS-related co-morbidities.
PMID- 25851234
TI - Complement system modulation as a target for treatment of arrhythmogenic
cardiomyopathy.
AB - Inflammation may contribute to disease progression in arrhythmogenic
cardiomyopathy (ACM). However, its role in this process is unresolved. Our goal
was to delineate the pathogenic role of the complement system in a new animal
model of ACM and in human disease. Using cardiac histology, echocardiography, and
electrocardiography, we have demonstrated that the desmin-null mouse (Des-/-)
recapitulates most of the pathognomonic features of human ACM. Massive complement
activation was observed in the Des-/- myocardium in areas of necrotic cells
debris and inflammatory infiltrate. Analysis of C5aR-/-Des-/- double-null animals
and a pharmaceutical approach using a C5a inhibitor were used to delineate the
pathogenic role of the complement system in the disease progression. Our findings
indicate that inhibiting C5aR (CD88) signaling improves cardiac function,
histopathology, arrhythmias, and survival after endurance. Containment of the
inflammatory reaction at the initiation of cardiac tissue injury (2-3 weeks of
age), with consequently reduced myocardial remodeling and the absence of a direct
long-lasting detrimental effect of C5a-C5aR signaling on cardiomyocytes, could
explain the beneficial action of C5aR ablation in Des-/- cardiomyopathy. We
extend the relevance of these findings to human pathophysiology by showing for
the first time significant complement activation in the cardiac tissues of
patients with ACM, thus suggesting that complement modulation could be a new
therapeutic target for ACM.
PMID- 25851235
TI - Transcriptional networks implicated in human nonalcoholic fatty liver disease.
AB - The transcriptome of nonalcoholic fatty liver disease (NAFLD) was investigated in
several studies. However, the implications of transcriptional networks in
progressive NAFLD are not clear and mechanisms inducing transition from
nonalcoholic simple fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) are
still elusive. The aims of this study were to (1) construct networks for
progressive NAFLD, (2) identify hub genes and functional modules in these
networks and (3) infer potential linkages among hub genes, transcription factors
and microRNAs (miRNA) for NAFLD progression. A systems biology approach by
combining differential expression analysis and weighted gene co-expression
network analysis (WGCNA) was utilized to dissect transcriptional profiles in 19
normal, 10 NAFL and 16 NASH patients. Based on this framework, 3 modules related
to chromosome organization, proteasomal ubiquitin-dependent protein degradation
and immune response were identified in NASH network. Furthermore, 9 modules of co
expressed genes associated with NAFL/NASH transition were found. Further
characterization of these modules defined 13 highly connected hub genes in NAFLD
progression network. Interestingly, 11 significantly changed miRNAs were
predicted to target 10 of the 13 hub genes. Characterization of modules and hub
genes that may be regulated by miRNAs could facilitate the identification of
candidate genes and pathways responsible for NAFL/NASH transition and lead to a
better understanding of NAFLD pathogenesis. The identified modules and hub genes
may point to potential targets for therapeutic interventions.
PMID- 25851236
TI - Genome-wide analysis of the family 1 glycosyltransferases in cotton.
AB - Family 1 GT, designated as UGT, is the largest and most functionally important
multigene family in the plant kingdom. In this study, we carried out a genome
wide identification, analysis, and comparison of 142, 146, and 196 putative UGTs
from Gossypium raimondii, Gossypium arboreum, and Gossypium hirsutum,
respectively. All members present the 44 amino-acid conserved consensus sequence
termed the plant secondary product glycosyltransferase motif. According to the
phylogenetic relationship among the cotton UGT proteins and those from other
species, GrUGTs and GaUGTs could be classified into 16 major phylogenetic groups
(A-P), whereas GhUGTs are classified into 15 major phylogenetic groups with a
lack of group C. All cotton UGTs are dispersed throughout the chromosomes and are
displayed in clusters with the same open reading frame orientation. The expansion
of them appears to result from genome duplication and rearrangement. Two
conserved introns, A and B, are detected in most of the intron-containing-UGTs in
G. raimondii and G. arboreum, whereas only intron A is detected in the intron
containing-UGTs in G. hirsutum. Furthermore, expression patterns of the UGT genes
in G. hirsutum wild type and its near isogenic fuzzless-lintless mutant at the
stage of fiber initiation were analyzed using the RNA-seq data. Overall, this
study not only deepens our understanding of the structure, phylogeny, evolution,
and expression of cotton UGT genes, but also provides a solid foundation for
further cloning and functional studies of the UGT family genes.
PMID- 25851237
TI - Identification and characterization of paternal-preferentially expressed gene NF
YC8 in maize endosperm.
AB - Gene imprinting describes an epigenetic phenomenon, whereby genetically identical
alleles are differentially expressed dependent on parent-of-origin. Some
imprinted genes belonged to NUCLEAR FACTOR Y (NF-Y) transcription factors, which
were involved in many important metabolic processes in plant. The
characterizations of imprinted genes are of great importance for their function
exploration. In this paper, 15 non-redundant NF-YC genes were identified in the
maize genome and the paternally expressed gene NF-YC8 was further analyzed. NF
YC8 primarily expressed in maize immature ear and tassel and phylogenetic
analysis showed that NF-YC8 was highly homologous with Arabidopsis thaliana NF
YC2 genes which function in regulation of the flowering processes, ER stress
response. Furthermore, NF-YC8 was a differential, gene-specific imprinted gene at
14 DAP and persistently imprinted throughout later endosperm development in the
B73/Mo17 genetic background. Bisulfite sequencing for NF-YC8 in maize endosperm
showed that the paternal alleles were higher methylated (CG, CHG and CHH
contexts) than maternal alleles in the 5' upstream region, and the coding region
was highly methylated in CG context. Additionally, TE (CG, CHG and CHH contexts)
and repetitive region (CG and CHG contexts) were all highly methylated. These
results are the first description of evolution and molecular characterization of
maize NF-YC8 and will provide new references for maize NF-YC genetic analysis.
PMID- 25851238
TI - Post-Disaster Mental Health Among Parent-Child Dyads After a Major Earthquake in
Indonesia.
AB - The interdependent adjustment of children and their parents following disasters
has been well documented. We used the Actor-Partner Interdependence Model (APIM)
to provide an appropriate analytical framework for examining how family members
may contribute to each other's post-disaster mental health. Independent self
reports were collected from parent-child dyads (n = 397) residing in a rural
community in Indonesia that was devastated by a major earthquake. Elementary
school children (M = 10 years; 51 % female) and one of their parents (M = 41
years; 73 % female) each reported on their disaster exposure, posttraumatic
stress (PTS) symptoms, and general distress. The APIM was used to examine mental
health within dyads and moderation by gender across dyads. Children reported
lower disaster exposure and fewer PTS symptoms, but similar general distress
levels, as their parents. Children's and parents' disaster-specific PTS symptoms
were the strongest predictor of their own general distress. Parents' PTS symptoms
were associated with children's general distress (b = 0.14, p < 0.001), but
children's PTS symptoms were not associated with parents' general distress (b =
0.02, p > 0.05). Findings were not moderated by parents' or children's gender.
Although children and parents may respond differently to natural disasters, they
may be best understood as a dyad. APIM analyses provide new evidence suggesting a
unidirectional path of influence from parents' disaster-related symptomatology to
children's general mental health. Dyadic approaches to understanding mental
health and treating symptoms of distress among disaster survivors and their
families following trauma are encouraged.
PMID- 25851240
TI - Spirituality and/or religious faith: A means for coping with the effects of
amyotrophic lateral sclerosis/motor neuron disease?
AB - OBJECTIVE: The notion of spirituality/religious belief is recognized
internationally as a domain within end-of-life care and is important in patients'
and carers' quality-of-life. When faced with incurable illness, patients often
become more philosophical about their life; many seek comfort in spiritual or
religious philosophies. Our intention was to understand how personal spirituality
and religious faith might help those living with amyotrophic lateral
sclerosis/motor neuron disease (ALS/MND) cope with their impending death. METHOD:
Unsolicited narratives (internet and print-published) written by individuals
diagnosed with the terminal condition of ALS/MND were analyzed thematically.
Narratives from 161 individuals diagnosed with ALS/MND written over a period of
37 years (from 1968 to 2005) were included. RESULTS: Our findings reveal that
religious faith sustains and helps people to avoid despair, and personal
spirituality helps them make sense of what is happening to them. SIGNIFICANCE OF
RESULTS: The use of personal narratives by people with ALS/MND has provided a
vehicle for sharing their deepest spiritual and religious thoughts with others.
The place of spirituality and religious faith within ALS/MND care should not be
underestimated. Assessment of religious or spiritual needs should become a
routine part of practice and is the responsibility of all members of the
multidisciplinary team.
PMID- 25851239
TI - The Potential Utility of Eye Movements in the Detection and Characterization of
Everyday Functional Difficulties in Mild Cognitive Impairment.
AB - Mild cognitive impairment (MCI) refers to the intermediate period between the
typical cognitive decline of normal aging and more severe decline associated with
dementia, and it is associated with greater risk for progression to dementia.
Research has suggested that functional abilities are compromised in MCI, but the
degree of impairment and underlying mechanisms remain poorly understood. The
development of sensitive measures to assess subtle functional decline poses a
major challenge for characterizing functional limitations in MCI. Eye-tracking
methodology has been used to describe visual processes in everyday, naturalistic
action among healthy older adults as well as several case studies of severely
impaired individuals, and it has successfully differentiated healthy older adults
from those with MCI on specific visual tasks. These studies highlight the promise
of eye-tracking technology as a method to characterize subtle functional decline
in MCI. However, to date no studies have examined visual behaviors during
completion of naturalistic tasks in MCI. This review describes the current
understanding of functional ability in MCI, summarizes findings of eye-tracking
studies in healthy individuals, severe impairment, and MCI, and presents future
research directions to aid with early identification and prevention of functional
decline in disorders of aging.
PMID- 25851241
TI - Prevalence of polymorphisms with significant resistance to NS5A inhibitors in
treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden.
AB - BACKGROUND: The future treatment of hepatitis C virus (HCV) infection will be
combinations of direct-acting antivirals (DAAs) that not only target multiple
viral targets, but are also effective against different HCV genotypes. Of the
many drug targets in HCV, one promising target is the non-structural 5A protein
(NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir,
have shown potent efficacy. However, since HCV is known to have very high
sequence diversity, development of resistance is a problem against but not
limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and
NS5B non-nucleoside inhibitors), when used in suboptimal combinations.
Furthermore, it has been shown that natural resistance against DAAs is present in
treatment-naive patients and such baseline resistance will potentially complicate
future treatment strategies. METHODS: A pan-genotypic population-sequencing
method with degenerated primers targeting the NS5A region was developed. We have
investigated the prevalence of baseline resistant variants in 127 treatment-naive
patients of HCV genotypes 1a, 1b, 2b and 3a. RESULTS: The method could
successfully sequence more than 95% of genotype 1a, 1b and 3a samples.
Interpretation of fold resistance data against the NS5A inhibitors was done with
the help of earlier published phenotypic data. Baseline resistance variants
associated with high resistance (1000-50,000-fold) was found in three patients:
Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient.
CONCLUSION: Using this method, baseline resistance can be examined and the data
could have a potential role in selecting the optimal and cost-efficient treatment
for the patient.
PMID- 25851242
TI - Seroprevalence of Toxoplasma gondii in Western Romania.
AB - Toxoplasma gondii is an obligate intracellular parasite that most commonly causes
asymptomatic infection in immunocompetent hosts, but can have devastating
consequences in congenitally infected infants and immunocompromised patients. We
evaluated the seroprevalence of T. gondii in the general population in Western
Romania. Sera from 304 individuals were analysed with the Pastorex Toxo test,
which allows the simultaneous detection of T. gondii IgG and/or IgM antibodies.
T. gondii antibodies were demonstrated in 197 individuals (64.8%) and the
prevalence increased with age: 35.0% in those < 20 years versus 76.8% in those >=
70 years (p < 0.001). There was a higher prevalence of T. gondii antibodies in
rural areas (76.9%) than in urban regions (55.3%) (p < 0.001). Our results
suggest a high prevalence of T. gondii antibodies in Western Romania.
PMID- 25851243
TI - Patterns of outpatient ceftriaxone use in a Japanese general hospital: an
increased need for development of outpatient parenteral antimicrobial therapy
programs.
PMID- 25851244
TI - Ventilator-associated pneumonia rates after introducing selective digestive tract
decontamination.
AB - The incidence of ventilator-associated pneumonia (VAP) before and after the
introduction of selective oral decontamination (SOD) only and selective digestive
tract decontamination (SDD) in a general intensive care population was examined.
SOD as standard of care was introduced in December 2010 and SDD, including SOD,
in January 2012 for all patients with an expected length of intensive care unit
(ICU) stay of at least 48 h. The diagnosis of VAP was based on clinical criteria
and quantitative cultures of bronchoalveolar lavage fluid. A total of 4945
mechanically ventilated patients accounting for 37 554 ventilator days in the
period from 2005 to 2013 were analyzed. The incidence of VAP per 1000 ventilator
days declined significantly from 4.38 +/- 1.64 before to 1.64 +/- 0.43 after
introduction of SOD/SDD (p = 0.007). Implementation of SOD/SDD as standard of
care in ICUs may thus be effective in preventing VAP.
PMID- 25851245
TI - The voices of breastfeeding resource nurses.
AB - OBJECTIVE: To describe and evaluate the Breastfeeding Resource Nurse (BRN) role
and program at The Children's Hospital of Philadelphia (CHOP). DESIGN: The
primary study was a multimethod study including a survey and key informant
interviews to meet the study's objectives: to describe how the BRN implements his
or her role at the unit level throughout the hospital, to describe the successes
and challenges of the BRN role, to provide data on how BRNs may be better
supported in their roles, and provide data for the translation of the BRN program
to other institutions. We present the qualitative descriptive component from the
primary study. SETTING: The Children's Hospital of Philadelphia enterprise.
PARTICIPANTS: Eighteen BRNs within the CHOP enterprise. METHODS: Semistructured
interviews were conducted with the BRN participants. The data were analyzed with
conventional content analysis. RESULTS: Four major themes emerged from the BRN
interview data: Empowering through evidence, Advocacy, Going the extra mile, and
Personal connections to breastfeeding. CONCLUSIONS: Compelling stories
illustrated the role of the BRN as patient advocate and educator for staff and
families. Knowing the evidence about lactation and breastfeeding empowered the
BRN to be successful in his or her role. The BRNs derived great personal and
professional satisfaction from their roles. The BRN program can be easily adapted
to other pediatric care centers and will enable improved breastfeeding outcomes
at the point of care.
PMID- 25851248
TI - The 'warm' side of coldness: Cold promotes interpersonal warmth in negative
contexts.
AB - The concrete experience of physical warmth has been demonstrated to promote
interpersonal warmth. This well-documented link, however, tells only half of the
story. In the current study, we thus examined whether physical coldness can also
increase interpersonal warmth under certain circumstances. We conducted three
experiments to demonstrate that the relationship between the experience of
physical temperature and interpersonal outcomes is context dependent. Experiment
1 showed that participants touching cold (vs. warm) objects were more willing to
forgive a peer's dishonest behaviour. Experiment 2 demonstrated the fully
interactive effect of temperature and context on interpersonal warmth:
Participants touching cold (vs. warm) objects were less likely to assist an
individual who had provided them with good service (positive social context), but
more likely to assist an individual who had provided them with poor service
(negative social context). Experiment 3 replicated the results of Experiment 2
using the likelihood to complain, a hostility-related indicator, as the dependent
variable: In a pleasant queue (positive social context), participants touching
cold objects were more likely to complain and those touching warm objects were
less likely to complain compared with the control group. This pattern was
reversed in an annoying queue (negative social context).
PMID- 25851249
TI - Impact of residual (18)F-fluoride in (18)F-FDOPA for the diagnosis of
neuroblastoma.
AB - OBJECTIVE: PET imaging with (18)F-FDOPA has been successfully applied in the
diagnosis and surveillance of neuroblastoma (NB) by targeting the overexpression
of aromatic L-amino acid decarboxylase. This study aims to assess the impact of
residual (18)F-fluoride on (18)F-FDOPA PET in NB and to implement a method to
maintain low (18)F-fluoride content in future studies. METHODS: Automatic
synthesis of (18)F-FDOPA was based on the electrophilic method using TRACERlab
FXFE module. Radio-TLC was employed to determine residual (18)F-fluoride levels.
We analyzed the impact of residual (18)F-fluoride on the images of 35 patients
undergoing (18)F-FDOPA PET at initial diagnosis and/or follow-ups of NB. RESULTS:
In 35 batches of (18)F-FDOPA products from 9/28/2010 to 07/27/2011, the mean
residual (18)F-fluoride level was 4.4 % (range 0.2-19.1 %). Residual (18)F
fluoride level >=4.0 % was associated with dense uptake in the growth plates,
skull, and pelvis on PET scans, which may interfere with the interpretation of
(18)F-FDOPA imaging in NB. By applying stringent restraints in (18)F-FDOPA
production, including regular renewal of reagents, exclusive use of NH4OH, and
timely replacement of HPLC column, the incidence of (18)F-FDOPA batches with
residual (18)F-fluoride level >=4.0 % was reduced from 33 to 4 % (P < 0.0001)
during 7/30/2011-4/29/2013. CONCLUSION: By monitoring residual (18)F-fluoride
levels and keeping stringent restraint procedures, low (18)F-fluoride content was
achieved in most batches of (18)F-FDOPA, which diminished false-positive skeletal
uptake. An appropriate upper limit of (18)F-fluoride level is suggested to be
included in the criteria of routine quality control of (18)F-FDOPA productions.
PMID- 25851247
TI - Carboxypeptidase B2 deficiency reveals opposite effects of complement C3a and C5a
in a murine polymicrobial sepsis model.
AB - BACKGROUND AND OBJECTIVES: Carboxypeptidase B2 (CPB2) is a basic carboxypeptidase
with fibrin and complement C3a and C5a as physiological substrates. We
hypothesized that in polymicrobial sepsis, CPB2-deficient mice would have
sustained C5a activity, leading to disease exacerbation. METHODS: Polymicrobial
sepsis was induced by cecal ligation and puncture (CLP). RESULTS: Contrary to our
hypothesis, Cpb2(-/-) mice had significantly improved survival, with reduced lung
edema, less liver and kidney damage, and less disseminated intravascular
coagulation. Hepatic pro-CPB2 was induced by CLP, leading to increased pro-CPB2
levels. Thrombomodulin present on mesothelium supported thrombin activation of
pro-CPB2. Both wild-type and Cpb2(-/-) animals treated with a C5a receptor
antagonist had improved survival, demonstrating that C5a was detrimental in this
model. Treatment with a fibrinolysis inhibitor, tranexamic acid, caused a
decrease in survival in both genotypes; however, the Cpb2(-/-) animals retained
their survival advantage. Administration of a C3a receptor antagonist exacerbated
the disease in both wild-type and Cpb2(-/-) mice and eliminated the survival
advantage of Cpb2(-/-) mice. C5a receptor is expressed in both peritoneal
macrophages and neutrophils; in contrast, C3a receptor expression is restricted
to peritoneal macrophages, and C3a induced signaling in macrophages but not
neutrophils. CONCLUSIONS: While C5a exacerbates the peritonitis, resulting in a
deleterious generalized inflammatory state, C3a activation of peritoneal
macrophages may limit the initial infection following CLP, thereby playing a
diametrically opposing protective role in this polymicrobial sepsis model.
PMID- 25851250
TI - Gonadotropin-releasing hormone receptor-targeted paclitaxel-degarelix conjugate:
synthesis and in vitro evaluation.
AB - To increase the selectivity of chemotherapeutic agents, receptor-mediated tumor
targeting approaches have been developed. Here, degarelix [Ac-D-Nal-D-Cpa-D-Pal
Ser-Aph(L-Hor)-D-Aph(Cbm)-Leu-ILys-Pro-D-Ala-NH2], a gonadotropin-releasing
hormone antagonist, was employed as a targeting moiety for paclitaxel (PTX). Five
PTX-degarelix conjugates were synthesized, in which PTX was attached via
disulfide bond to the different position in the degarelix sequence. All of the
PTX-degarelix conjugates exhibited a half-life greater than 10 h determined in
human serum. A fluorometric imaging plate reader assay showed that the conjugates
LK-MY-9 and LK-MY-10 had an antagonism efficacy similar to that of degarelix. The
in vitro cytostatic effects of the conjugates were determined by a (3-(4,5
dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
tetrazolium) (MTS) assay, and the 50% inhibitory concentration value of the
conjugates on 3T3 mouse embryonic fibroblast cells were one order of magnitude
higher than the 50% inhibitory concentration values of the conjugates on MCF-7
human breast cancer cells and HT-29 human colon cancer cells. Receptor saturation
tests further demonstrated that pre-incubation of the cells with degarelix
reduced the efficacy of LK-MY-10 in a concentration-dependent manner. In
conclusion, degarelix is a valid and stable moiety that has great potential for
targeting chemotherapy drugs.
PMID- 25851251
TI - Development and optimisation of 3-Acetyl-11-keto-beta-boswellic acid loaded poly
lactic-co-glycolic acid-nanoparticles with enhanced oral bioavailability and in
vivo anti-inflammatory activity in rats.
AB - OBJECTIVES: 3-Acetyl-11-keto-beta-boswellic acid (AKBA) is a potent anti
inflammatory compound of Boswellia serrata. However, anti-inflammatory activity
of AKBA is impeded by poor oral bioavailability due to its poor aqueous
solubility. In this context, we aimed to develop poly lactic-co-glycolic acid
(PLGA)-based nanoparticle formulation of AKBA (AKBA-NPs) in order to improve its
oral bioavailability and in-vivo anti-inflammatory activity in rats. METHODS:
AKBA-NPs were prepared and characterised by analysing particle size and zeta
potential using zeta sizer, surface morphology by scanning electron microscopy
and transmission electron microscopy, and physical property using differential
scanning calorimetry and X-ray diffraction techniques. The optimised
nanoparticles were evaluated for in-vitro drug release and oral bioavailability
studies, and in-vivo anti-inflammatory activity by carrageenan-induced rat paw
oedema method. KEY FINDINGS: The optimised AKBA-NPs showed the particle size of
179.6 nm with 0.276 polydispersity index and entrapment efficiency of 82.5%. AKBA
NPs showed increased in-vivo anti-inflammatory activity as compared with AKBA.
Bioavailability study revealed about six times higher peak plasma concentration
of AKBA in AKBA-NPs. Moreover, t1/2 and total area under the curve of AKBA were
also enhanced by two and ninefold, respectively, in AKBA-NPs as compared with
corresponding AKBA. CONCLUSIONS: The promising results of improved oral
bioavailability and in-vivo anti-inflammatory activity of AKBA suggested the
successful nanoparticle formulation of AKBA.
PMID- 25851252
TI - Palladium-Catalyzed Dynamic Kinetic Asymmetric Transformation of Racemic Biaryls:
Axial-to-Central Chirality Transfer.
AB - The first dynamic kinetic asymmetric transformation of racemic biaryl substrates
on the basis of axial-to-central chirality transfer has been realized. Chiral Pd
NHC complexes were found to catalyze the dynamic kinetic asymmetric
spiroannulation of 4-(2-bromoaryl)-naphthalen-1-ols (or 2'-bromo-[1,1'-biphenyl]
4-ols) with internal alkynes, affording a series of enantioenriched spirocyclic
products bearing an all-carbon quaternary stereocenter in good yields (up to 95%)
with excellent enantioselectivities (up to 97% ee).
PMID- 25851253
TI - Invited Editorial: MERS-CoV An Emerging Viral Zoonotic Disease: Three Years After
and Counting.
PMID- 25851254
TI - Chikungunya, the 2014, emerging infectious diseases in the Americas.
PMID- 25851255
TI - Malaria by Plasmodium knowlesi, A Zoonosis Transmitted by Vectors.
PMID- 25851257
TI - Frequency and clinical relevance of inconsistent code status documentation.
AB - BACKGROUND: Accurate and complete documentation of hospitalized patients' code
status is important to ensure that healthcare providers take appropriate action
in the event of a cardiac arrest. OBJECTIVE: Determine the frequency and clinical
relevance of incomplete and inconsistent code status documentation. DESIGN: Point
prevalence study. SETTING: Academic medical centers. PATIENTS: Patients admitted
to general internal medicine wards. MEASUREMENTS: Frequency and clinical
relevance of inconsistent code status documentation across 5 documentation
sources. RESULTS: Thirty-eight (20%; 95% confidence interval [CI], 14%-26%) of
187 patients had complete and consistent code status documentation. Another 27
(14%; 95% CI, 9%-19%) patients had no code status documentation. The remaining
122 (65%; 95% CI, 58%-72%) patients had at least 1 code status documentation
inconsistency. Of these, 38 (20%; 95% CI, 14%-26%) patients had a clinically
relevant code status documentation inconsistency. Multivariate logistic
regression analysis demonstrated that increased age (odds ratio [OR] = 1.07 [95%
CI, 1.05-1.10] for every 1-year increase in age, P < 0.001) and patients
receiving comfort measures (OR = 9.39 [95% CI, 1.35-65.19], P = 0.02) were
independently associated with a clinically relevant code status documentation
inconsistency. CONCLUSIONS: Incomplete and inconsistent documentation of code
status occurred frequently in hospitalized patients, especially elderly patients
and patients receiving comfort measures. Having multiple, poorly integrated code
status documentation sources leads to a significant number of concerning
inconsistencies that create opportunities for healthcare providers to
inappropriately deliver or withhold resuscitative measures that conflict with
patients' expressed wishes. Institutions need to be aware of this potential
documentation hazard and take steps to minimize code status documentation
inconsistencies.
PMID- 25851258
TI - Effect of commercial starter cultures on volatile compound profile and sensory
characteristics of dry-cured foal sausage.
AB - BACKGROUND: The present work deals with the evaluation of the effect of three
different commercial starter cultures (Chr. Hansen, Horsholm, Denmark) on the
volatile compound profile and sensory properties, as well as some important
physicochemical parameters, of dry-fermented foal sausages at the end of ripening
in order to select the most suitable starter culture for this elaboration. The
sausage batches were named as follows: CO (non-inoculated control), FS
(Lactobacillus sakei + Staphylococcus carnosus), SM (L. sakei + S. carnosus +
Staphylococcus xylosus + Pediococcus pentosaceus + Debaryomyces hansenii) and TR
(L. sakei + S. carnosus +S. xylosus). RESULTS: The pH values differed
significantly among batches, with the highest values corresponding to CO followed
by TR, SM and FS. The highest amounts of volatile compounds were found in FS
batch. Hexanal was the most abundant compound, especially in FS and SM batches.
These batches also showed higher levels of compounds derived from carbohydrate
fermentation and amino acid catabolism. Sensory results showed that acid taste
was significantly lower in CO batch than in inoculated batches. CONCLUSION:
According to most parameters, batches inoculated with FS and SM starters showed
marked acidity compared with TR and CO batches, as expected from the
manufacturer's indications. Therefore the most suitable starter culture for use
in the manufacture of foal sausages in Mediterranean countries such as Spain with
a preference for low-acidity products was found to be TR culture.
PMID- 25851259
TI - The Uptake of GABA in Trypanosoma cruzi.
AB - Gamma aminobutyric acid (GABA) is widely known as a neurotransmitter and signal
transduction molecule found in vertebrates, plants, and some protozoan organisms.
However, the presence of GABA and its role in trypanosomatids is unknown. Here,
we report the presence of intracellular GABA and the biochemical characterization
of its uptake in Trypanosoma cruzi, the etiological agent of Chagas' disease.
Kinetic parameters indicated that GABA is taken up by a single transport system
in pathogenic and nonpathogenic forms. Temperature dependence assays showed a
profile similar to glutamate transport, but the effect of extracellular cations
Na(+) , K(+) , and H(+) on GABA uptake differed, suggesting a different uptake
mechanism. In contrast to reports for other amino acid transporters in T. cruzi,
GABA uptake was Na(+) dependent and increased with pH, with a maximum activity at
pH 8.5. The sensitivity to oligomycin showed that GABA uptake is dependent on ATP
synthesis. These data point to a secondary active Na(+) /GABA symporter energized
by Na(+) -exporting ATPase. Finally, we show that GABA occurs in the parasite's
cytoplasm under normal culture conditions, indicating that it is regularly taken
up from the culture medium or synthesized through an still undescribed metabolic
pathway.
PMID- 25851260
TI - (1->3)-beta-D-glucan and galactomannan testing for the diagnosis of fungal
peritonitis in peritoneal dialysis patients, a pilot study.
AB - Fungal peritonitis is an uncommon but serious complication of peritoneal dialysis
(PD) due to the fact that routine culture to recovered the etiologic agents are
time consuming and KOH staining has very low sensitivity. Peritoneal (1->3)-beta
D-glucan (BG) or galactomannan (GM), both fungal cell wall components, are
candidate biomarkers of fungal peritonitis. Hence, a comparative cross-sectional
analysis of peritoneal dialysis fluid (PDF) BG (Fungitell, Cape Cod, MA, USA) and
GM (Platelia Aspergillus Ag kits, Bio-rad, France) from all PD patients with and
without fungal peritonitis (13 cases, identified by culture), over a 1 year
period, was performed. PDF of the fungal peritonitis group showed very high BG
(494 +/- 19 pg/ml) and high GM (3.41 +/- 1.24) similar results were noted in
specimens from cases of peritonitis with other causes, especially gram negative
bacterial peritonitis. A BG cut-off value at 240 pg/ml and GM at 0.5 showed
sensitivity/ specificity at 100%/ 83% and 77%/ 58%, respectively. A concomitantly
positive GM reduced the false positive rate of BG from nonfungal peritonitis. In
conclusion, BG and GM in peritoneal fluid with provisional cut-off values were
applicable as surrogate biomarkers for the diagnosis of fungal peritonitis in PD
patients.
PMID- 25851261
TI - MALDI-TOF MS-based identification of black yeasts of the genus Exophiala.
AB - In this study, we investigated the applicability of matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the
identification of Exophiala species. The analysis included a total of 110
Exophiala isolates, including 15 CBS strains representing 4 species, Exophiala
dermatitidis (61), E. phaeomuriformis (36), E. crusticola (9), and E.
heteromorpha (4), that had been previously identified based on internal
transcribed spacer (ITS) regions. We also compared the relative efficacies of
Sabouraud glucose agar (SGA) and Columbia agar (CA) for use in MALDI-TOF MS.
Remarkably, we obtained a log-score value >=2.0 by using either SGA or CA for all
15 CBS strains, indicating species-level identification. The remaining 95
Exophiala strains were identified to the genus or species levels, with
identification rates of 96.8% and 90.5%, using SGA or CA, respectively. Most of
the E. dermatitidis (100% and 92.9%), E. phaeomuriformis (80.6% and 83.9%), E.
crusticola (50% and 100%), and E. heteromorpha (100% and 100%) isolates were
correctly identified using SGA or CA, respectively. Furthermore, 58.9% and 26.3%
of the strains had log-score values of >=2.0 by using SGA and CA, respectively.
Our results indicate that MALDI-TOF MS is a rapid and reliable technique with
high rates of correct taxonomic identification.
PMID- 25851262
TI - Genome sequence comparison of Aspergillus fumigatus strains isolated from
patients with pulmonary aspergilloma and chronic necrotizing pulmonary
aspergillosis.
AB - Aspergillus fumigatus is the Aspergillus species most commonly associated with
aspergillosis. Of the various presentations of aspergillosis, one of the most
frequently observed in cases involving A. fumigatus pulmonary infections is
aspergilloma (PA). In such infections one finds a fungus ball composed of fungal
hyphae, inflammatory cells, fibrin, mucus, and tissue debris. Chronic necrotizing
pulmonary aspergillosis (CNPA), also known as semi-invasive or invasive
aspergillosis, is locally invasive and predominantly seen in patients with mild
immunodeficiency or with a chronic lung disease. In the present study, with the
aid of a next-generation sequencer, we conducted whole genome sequence (WGS)
analyses of 17 strains isolated from patients in Japan with PA and CNPA. A total
of 99,088 SNPs were identified by mapping the reads to A. fumigatus genome
reference strain Af293, and according to genome-wide phylogenetic analysis, there
were no correlations between the whole genome sequence typing results and
pathologic conditions of patients. Here, we conducted the first multi-genome WGS
study to focus on the A. fumigatus strains isolated from patients with PA and
CNPA, and comprehensively characterized genetic variations of strains. WGS
approach will help in better understanding of molecular mechanisms of
aspergillosis cases caused by A. fumigatus.
PMID- 25851263
TI - First report of Veronaea botryosa as a causal agent of chromomycosis in frogs.
AB - A dematiaceous hyphomycete, isolated from frogs, was determined as the possible
etiologic agent of a case of systemic chromomycosis this cold-blooded animal. The
fungus was identified as Veronaea botryosa on the basis of morphological features
observed in histopathological examination and molecular phylogenetic evidence.
Although V. botryosa is known to be distributed widely in litter and as a human
pathogen, this is the first confirmed report of its involvement in a lethal
infection in a cold-blooded animal, including an anuran.
PMID- 25851264
TI - Efficacy of Ethanol against Trichosporon asahii Biofilm in vitro.
AB - Trichosporon asahii (T. asahii) can cause invasive infections, particularly
catheter-related bloodstream infections (CR-BSIs). T. asahii biofilm, which is
resistant to the most common clinical antifungal agents, may play an important
role in these life-threatening infections. This study focused on the effects of
ethanol on the different phases of T. asahii biofilm formation. At the
concentrations clinically used, ethanol killed T. asahii planktonic cells (MIC90
= 15% and m-MIC90 = 15%) and biofilm (SMIC90 = 50%), and exposure to 25% ethanol
for 12 h or to 50% ethanol for 8 h completely inhibited biofilm development and
eradicated mature T. asahii biofilm. Thus, our results showed that ethanol
effectively inhibited the main phases of T. asahii biofilm formation. This study
reveals a new potential strategy to prevent and treat T. asahii biofilm-related
CR-BSIs.
PMID- 25851266
TI - Do anti-hypertensive renin-angiotensin system inhibitors contribute to the
development of classical Kaposi sarcoma?
PMID- 25851265
TI - Cytotoxic effects of aflatoxin B1 on human brain microvascular endothelial cells
of the blood-brain barrier.
AB - Aflatoxins are mycotoxins produced by Aspergillus spp. Although AFB1 is
implicated as a carcinogen in hepatocellular carcinoma, brain autopsies in
affected areas have revealed its presence in 81% of cases. Given its
haematogenous spread, here we determined the cytotoxic effects of AFB1 on primary
human brain microvascular endothelial cells (HBMEC), which constitute the blood
brain barrier, human umbilical vein endothelial cells (HUVEC) as well as
immortalized epithelial cells of human hepatocellular carcinoma (Huh7). The cell
types were exposed to AFB1 (3-32 nM) for 24 h and release of lactate
dehydrogenase was measured as cell cytotoxicity marker. Furthermore, DNA was
collected from both cell types and DNA adduct formation was determined by
immunoblot using anti-AFB1-DNA adduct antibody. At 32 nM, AFB1 killed >85% HBMEC,
while controls showed minimal effects (P < .05). Similar concentrations of AFB1
showed 22% cell death of HUVEC, while the same concentration did not kill Huh7.
At low concentrations, in other words, 3.2 nM, AFB1 produced DNA adduct formation
in HBMEC, while high concentration (32 nM) did not form DNA adducts. For HUVEC,
16 nM and 32 nM exhibited DNA adduct formation. For Huh7, 3.2 nM did not form DNA
adducts, while 32 nM exhibited DNA adduct formation. For the first time, we
report that AFB1 affected the viability of primary endothelial cells but not
immortalized Huh7 cells. Cytotoxicity of brain endothelial cells suggests extra
hepatic complications post-AFB1 exposure.
PMID- 25851267
TI - Diet and cognitive decline at middle age: the role of antioxidants.
AB - To assess the relationship between dietary intake of antioxidants (vitamin C,
vitamin E, beta-carotene, lutein, flavonoids and lignans) and cognitive decline
at middle age, analyses were performed on data from the population based
Doetinchem Cohort Study. Habitual diet and cognitive function were assessed twice
with a 5-year interval in 2613 persons aged 43-70 year at baseline (1995-2002).
Diet was assessed with a validated 178-item semi-quantitative FFQ. Cognitive
function was assessed with a neuropsychological test battery, consisting of the
15 Words Learning Test, the Stroop Test, the Word Fluency test, and the Letter
Digit Substitution Test. Scores on global cognitive function, memory, processing
speed, and cognitive flexibility were calculated. In regression analyses,
quintiles of antioxidant intake were associated with change in cognitive domain
scores. Results showed that higher lignan intake was linearly associated with
less decline in global cognitive function (P= 0.01), memory (P< 0.01) and
processing speed (P= 0.04), with about two times less declines in the highest v.
the lowest quintile. In the lowest quintile of vitamin E intake, decline in
memory was twice as fast as in all higher quintiles (P< 0.01). Global cognitive
decline in the highest lutein intake group was greater than in the lowest intake
group (P< 0.05). Higher flavonoid intake was associated with greater decline in
cognitive flexibility (P for trend = 0.04). Intakes of other antioxidants were
not associated with cognitive decline. We conclude that within the range of a
habitual dietary intake, higher intake of lignans is associated with less
cognitive decline at middle age.
PMID- 25851268
TI - Antibiotics for asymptomatic bacteriuria.
AB - BACKGROUND: Asymptomatic bacteriuria is commonly detected in women aged up to 60
years, patients with diabetes, and the elderly. The benefit of antibiotic
treatment for this condition is controversial. OBJECTIVES: To assess the
effectiveness and safety of antibiotics treatment for asymptomatic bacteriuria in
adults. Specific objectives were to assess 1) the effectiveness of antibiotics
for preventing development of symptomatic UTI, UTI-related complications, overall
mortality, UTI-related mortality, and resolution of bacteriuria; 2) the
development of resistance to antibiotic treatment by comparing resistance of
grown bacteria in urine before and after therapy; and 3) the frequency of adverse
events. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised
Register up to 24 February 2015 through contact with the Trials' Search Co
ordinator using search terms relevant to this review. SELECTION CRITERIA:
Randomised controlled trials (RCTs) and quasi-RCTs comparing antibiotics to
placebo or no treatment for asymptomatic bacteriuria in adults were included. The
outcomes of interest were the development of symptomatic urinary tract infection
(UTI), complications, death, any adverse event, development of antibiotic
resistance, bacteriological cure, and decline in kidney function. DATA COLLECTION
AND ANALYSIS: Two authors independently extracted the data and assessed study
quality. Statistical analyses were performed using the random effects model and
the results expressed as risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS: We included nine studies (1614 participants) in this review.
Symptomatic UTI (RR 1.11, 95% CI 0.51 to 2.43), complications (RR 0.78, 95% CI 0.
35 to 1.74), and death (RR 0.99, 95% CI 0.70 to 1.41) were similar between the
antibiotic and placebo or no treatment arms. Antibiotics were more effective for
bacteriological cure (RR 2.32, 95% CI 1.11 to 4.83) but also more adverse events
developed in this group (RR 3.77, 95% CI 1.40 to 10.15). No decline in the kidney
function was observed across the studies; minimal data were available on the
emergence of resistant strains after antimicrobial treatment.The included studies
were of medium and high quality, used different treatments for different
durations of treatment and follow-up, different populations, but this did not
appear to influence the results of review. AUTHORS' CONCLUSIONS: No differences
were observed between antibiotics versus no treatment of asymptomatic bacteriuria
for the development of symptomatic UTI, complications or death. Antibiotics were
superior to no treatment for the bacteriological cure but with significantly more
adverse events. There was no clinical benefit from treating asymptomatic
bacteriuria in the studies included in this review.
PMID- 25851269
TI - High tolerance and physiological mechanism of Zymomonas mobilis to phenolic
inhibitors in ethanol fermentation of corncob residue.
AB - Corncob residue as the lignocellulosic biomass accumulated phenolic compounds
generated from xylitol production industry. For utilization of this biomass,
Zymomonas mobilis ZM4 was tested as the ethanol fermenting strain and presented a
better performance of cell growth (2.8 * 10(8) CFU/mL) and ethanol
fermentability (54.42 g/L) in the simultaneous saccharification and fermentation
(SSF) than the typical robust strain Saccharomyces cerevisiae DQ1 (cell growth of
2.9 * 10(7) CFU/mL, ethanol titer of 48.6 g/L). The physiological response of Z.
mobilis ZM4 to the twelve typical phenolic compounds derived from lignocellulose
was assayed and compared with that of S. cerevisiae DQ1. Z. mobilis ZM4 showed
nearly the same tolerance to the phenolic aldehydes with S. cerevisiae DQ1, but
the stronger tolerance to the phenolic acids existing in corncob residue (2
furoic acid, p-hydroxybenzoic acid, p-coumaric acid, vanillic acid, ferulic acid,
and syringic acid). The tolerance mechanism of Z. mobilis was investigated in
terms of inhibitor degradation, cell morphology and membrane permeability under
the stress of phenolics using GC-MS, scanning and transmission electron
microscopies (SEM and TEM), as well as fluorescent probes. The results reveal
that Z. mobilis ZM4 has the capability for in situ detoxification of phenolic
aldehydes, and the lipopolysaccharide aggregation on the cell outer membrane of
Z. mobilis ZM4 provided the permeable barrier to the attack of phenolic acids.
PMID- 25851270
TI - Microphase Structure, Crystallization Behavior, and Wettability Properties of
Novel Fluorinated Copolymers Poly(perfluoroalkyl acrylate-co-stearyl acrylate)
Containing Short Perfluorohexyl Chains.
AB - Novel fluorinated copolymers of stearyl acrylate (SA) and (perfluorohexyl)ethyl
acrylate (C6A), (perfluorohexyl)ethyl methacrylate (C6MA), 2-[[[[2
(perfluorohexyl)]-sulfonyl]methyl] amino]ethyl acrylate (C6SA), and methacrylate
(C6SMA) were synthesized via miniemulsion copolymerization. The extremely
hydrophobic monomers perfluoroalkyl acrylate (FA) and SA acted as the reactive
costabilizer in the miniemulsion system. The microstructure and surface wetting
properties of the copolymers were characterized by (1)H NMR, FT-IR, and dynamic
contact angle test. The crystallization behaviors and fine surface structures of
the copolymer films were determined by differential scanning calorimetry (DSC)
and wide-angle X-ray diffraction (WAXD) analysis. The self-assembled aggregation
and roughness of the copolymer films were investigated by atomic force microscopy
(AFM). The results showed that the fluorinated side chains interrupted and
impeded the crystallizable side chains of SA from forming complete crystals. And
the Tm and DeltaHf of the copolymers were decreased as a consequence of this
effect. The fluorinated side chains in P(C6A/SA) and P(C6MA/SA) arranged between
the crystallizable hydrocarbon side chains of SA, while the crystallization
structure of fluorinated and nonfluorinated pendant groups existed all at once in
copolymers P(C6SA/SA) and P(C6SMA/SA). The four copolymers exhibited very low
surface free energy and excellent dynamic water repellency attributed to the
restriction of perfluoroalkyl groups combined with crystallization of stearyl
pendant groups.
PMID- 25851271
TI - Comparing long-term outcomes of primary and progressive carcinoma invading
bladder muscle after radical cystectomy.
AB - OBJECTIVE: To assess the impact of primary or progressive status on recurrence
free survival (RFS), cancer-specific mortality (CSM) and overall mortality (OM)
after radical cystectomy (RC) for muscle- invasive bladder cancer (MIBC).
PATIENTS AND METHODS: A total of 768 consecutive patients underwent RC as
treatment for MIBC at our institution between 2000 and 2012. Primary MIBC was
defined as no previous history of bladder cancer and progressive was defined as
recorded previous treated non-MIBC (NMIBC) that had progressed to MIBC. The
median follow-up was 85 (60-109) months. Univariate and multivariate Cox
regression models were used to compare RFS, CSM and OM between these two cohorts.
RESULTS: In all, 475 (61.8%) patients had primary and 293 (38.2%) patients had
progressive MIBC. There were no differences between the two groups in terms of
demographics, pathological and peri-operative complications (all P > 0.1). The 10
year RFS, CSM and OM rates for primary vs progressive status were 43 vs 36% (P =
0.01), 43 vs 37% (P = 0.01), and 35 vs 28% (P = 0.03), respectively. On
multivariable Cox regression analyses, progressive status remained significantly
associated with a higher rate of recurrence (hazard ratio [HR] 1.47, 95%
confidence interval [CI] 1.12-1.79; P = 0.03), CSM (HR 1.42, 95% CI 1.07-1.89; P
= 0.01) and OM (HR1.42, 95% CI 1.13-1.65; P = 0.02). CONCLUSIONS: Among patients
treated with RC for MIBC, progressive status was associated with a higher CSM, OM
and recurrence rate after RC. The present study thus provides an impetus to
improve risk sub-stratification when bladder cancer is still at the NMIBC stage,
be it through new biomarkers or improved imaging, as a subset of patients with
NMIBC are likely to benefit from early RC.
PMID- 25851272
TI - Drinking resumption: problematic alcohol use relapse after rehabilitation. A
phenomenological hermeneutical perspective.
AB - The majority of patients being treated for alcohol abuse disorders experience one
or more relapses after treatment. The fact that people use this inebriant in a
way leading to so much harm and suffering might seem a conundrum. Therapists,
family and others might find the person's relapse to be dramatic and upsetting,
and one might question whether the person has the sufficient will or motivation
to change. However, few previous studies have explored relapse from the patient's
perspective. The aim of this study was to illuminate the patient's lived
experience of relapse and to develop a deeper understanding of this phenomenon.
The study consisted of qualitative interviews using a phenomenological
hermeneutical approach. Three main themes emerged from the analyses: 'craving',
'self-image' and 'time'. The findings were discussed in the context of
phenomenological literature. Cravings could occur unpredictably; nevertheless,
craving was a common experience for the patients and signified a risk of relapse.
Bodily experiences of craving were frequently mentioned, and alcohol addiction
could be understood as to be a disease or a learned habit. Self-image was, at
times, adversely affected by relapse episodes. Therefore, feelings of shame, self
respect and recognition were significant concepts. This study found that the
perception of time as past, present and future greatly influenced the
participants' experiences of relapse and rehabilitation. Thus, relapse was an
upsetting and dramatic experience that could cause great discomfort and sometimes
life-threatening situations. However, relapse could also be viewed as a planned
event. This study highlights important truth and reality about alcoholism and
relapse grounded in people's lived experience.
PMID- 25851273
TI - Heterobi- and -trimetallic Ion Pairs of Zirconocene-Based Isoselective Olefin
Polymerization Catalysts with AlMe3.
AB - The reactivity towards AlMe3 of discrete cationic ansa-zirconocenes 2 a,b that
are ubiquitously used in isoselective propylene polymerization and based on
[{Ph(H)C(3,6-tBu2-Flu)(3-tBu-5-Et-Cp)}ZrMe2)] {Cp-Flu} and rac-[{Me2Si-(2-Me-4-Ph
Ind)2}ZrMe2] {SBI} was scrutinized. The first example of a structurally
characterized Group 4 metallocene AlMe3 adduct (3 b) is reported. In the presence
of excess AlMe3, the {SBI}-based AlMe3 adduct 3 b undergoes a slow decomposition
via C-H activation in a bridging methyl unit to yield a new species (4 b) with a
trimetallic {Zr(MU-CH2)(MU-Me)AlMe(MU-Me)AlMe2} core. EXSY NMR data for the
process 2 b?3 b->4 b suggest very rapid and reversible binding of an additional
AlMe3 molecule onto AlMe3 adduct 3 b. The resulting heterotrimetallic species
intermediates exchange of methyl groups between different metal centers and
slowly undergoes the C-H activation reaction towards 4 b.
PMID- 25851281
TI - Sins of omission and commission in systematic reviews in nursing: A commentary on
McRae et al. (2015).
PMID- 25851282
TI - Efficacy of concurrent superselective intra-arterial chemotherapy and
radiotherapy for late-stage squamous cell carcinoma of the temporal bone.
PMID- 25851283
TI - A prediction model for colon cancer surveillance data.
AB - Dynamic prediction models make use of patient-specific longitudinal data to
update individualized survival probability predictions based on current and past
information. Colonoscopy (COL) and fecal occult blood test (FOBT) results were
collected from two Australian surveillance studies on individuals characterized
as high-risk based on a personal or family history of colorectal cancer.
Motivated by a Poisson process, this paper proposes a generalized nonlinear model
with a complementary log-log link as a dynamic prediction tool that produces
individualized probabilities for the risk of developing advanced adenoma or
colorectal cancer (AAC). This model allows predicted risk to depend on a
patient's baseline characteristics and time-dependent covariates. Information on
the dates and results of COLs and FOBTs were incorporated using time-dependent
covariates that contributed to patient risk of AAC for a specified period
following the test result. These covariates serve to update a person's risk as
additional COL, and FOBT test information becomes available. Model selection was
conducted systematically through the comparison of Akaike information criterion.
Goodness-of-fit was assessed with the use of calibration plots to compare the
predicted probability of event occurrence with the proportion of events observed.
Abnormal COL results were found to significantly increase risk of AAC for 1 year
following the test. Positive FOBTs were found to significantly increase the risk
of AAC for 3 months following the result. The covariates that incorporated the
updated test results were of greater significance and had a larger effect on risk
than the baseline variables.
PMID- 25851284
TI - Heating-induced transition of Potyvirus Potato Virus A coat protein into beta
structure.
AB - In our previous communication, we have reported that virions of plant Potyvirus
Potato Virus A (PVA) have a peculiar structure characterized by high content of
disordered regions in intravirus coat protein (CP). In this report, we describe
unusual properties of the PVA CP. With the help of a number of physicochemical
methods, we have observed that the PVA CP just released from the virions by
heating at 60-70 degrees C undergoes association into oligomers and transition
to beta- (and even cross-beta-) conformation. Transition to beta-structure on
heating has been recently reported for a number of viral and non-viral proteins.
The PVA CP isolated by LiCl method was also transformed into cross-beta-structure
on heating to 60 degrees C. Using the algorithms for protein aggregation
prediction, we found that the aggregation-prone segments should be located in the
central region of a PVA CP molecule. Possibly this transition mimics some
functions of PVA CP in the virus life cycle in infected plants.
PMID- 25851285
TI - Renal impairment an impediment to heart transplantation?
AB - Chronic kidney disease and chronic heart failure are now recognized as closely
intertwined entities. The noxious interactions between the heart and kidney
systems as part of the so-called cardiorenal syndrome is a matter of great
concern for heart transplant candidates. Not only is chronic kidney disease a
commonly associated comorbidity, but its detrimental effect on the outcome of
heart transplantation is now well established. In the more advanced stages of
kidney disease, it may even deter physicians from carrying out heart
transplantation in potential candidates. This review offers insights on
epidemiological issues regarding chronic kidney disease among patients awaiting
heart transplantation as well as its impact on the outcomes related with heart
transplantations. Finally, emerging therapeutic opportunities which may benefit
heart transplant candidates with the most severe renal impairment will be
reviewed with a special emphasis on combined heart-kidney transplantation.
PMID- 25851286
TI - Immune disorders in hemodialysis patients.
AB - Immunologically, End Stage renal Disease (ESRD) is associated with some disorders
in both innate and adaptive immune system in such a form that there is a
coexistence of both immune activation and immune suppression. Although these
disorders are complex yet thoroughly unknown, there is a close relation between
the progressively defective immune system with side effects as well as mortality
causes including cardiovascular problems, infections, and malignancies. From the
other point, chronic inflammation as a major determinant of "dialysis syndrome"
(including malnutrition, cachexia, and vasculopathy) is considered as the main
factor of inability and mortality in dialysis patients. Such inflammation is
generally arisen from immune system response to uremia and individual's
repetitive contact with dialysis instruments and, in the long term, leads to
premature aging via intensifying tissue degeneration. Therefore, the immune
system is known as one of the most important therapeutic targets to reduce
morbidity and mortality in uremic and dialysis patients. This review addresses
different aspects as well as mechanisms of immune system dysfunction and possible
therapeutics in dialysis patients.
PMID- 25851287
TI - Vitamin E as adjuvant treatment for urinary tract infection in girls with acute
pyelonephritis.
AB - INTRODUCTION: Vitamin E is a fat-soluble vitamin that functions as an
antioxidant. The aim of this study was to investigate the effects of vitamins E
supplementation in combination with antibiotics for the treatment of girls with
acute pyelonephritis. MATERIALS AND METHODS: This double-blinded randomized
controlled trial was conducted on 152 girls aged 5 to 12 years with a first acute
pyelonephritis episode based on technetium Tc 99m dimercaptosuccinic acid (99mTc
DMSA). They were randomized to receive a 14-day treatment with only antibiotics
(control group; n = 76) and 14-day treatment with supplements of vitamin E
(intervention group; n = 76) in addition to the antibiotics. Patients' clinical
symptoms were monitored for 14 days and urine culture was performed 3 to 4 days
and 7 to 10 days after the start of the treatment and its completion,
respectively. All of the girls once underwent DMSA scan 4 to 6 months after the
treatment. RESULTS: During the follow-up days, the mean frequency of fever (P =
.01), urinary frequency (P = .001), urgency (P = .003), dribbling (P = .001), and
urinary incontinence (P = .006) were significantly lower in the intervention
group compared to the control group. There was no significant difference in the
results of urine culture 3 to 4 days after the start of treatment (P = .16) and 7
to 10 days after its termination (P = .37). There was also no significant
difference between the results of DMSA scan 4 to 6 months after the start of
treatment (P = .31). CONCLUSIONS: Vitamin E supplementation has a significant
effect in ameliorating sign and symptoms of UTI. However, further studies are
recommended to confirm these findings.
PMID- 25851288
TI - Evaluation of Th17 pathway in the diagnosis of autosomal dominant polycystic
kidney disease.
AB - INTRODUCTION: Current assessment tools of autosomal dominant polycystic kidney
disease (ADPKD) diagnosis are challenging. This study evaluated the possible
application of assessment of interleukin (IL)-17-related cytokines and the
circulatory T helper 17 cells in the diagnosis of ADPKD. MATERIALS AND METHODS:
Enrolling 54 ADPKD patients and 54 healthy individuals, we measured serum and
urine levels of IL-6, IL-17, IL-23, and transforming growth factor-beta and the
peripheral blood frequency of T helper 17 cells through flowcytometry. We
computed sensitivity and specificity of each inflammatory marker as well as their
different combinations using the receiver operating characteristic curve and
discriminant function analysis. RESULTS: The mean serum and urine levels of IL-17
and IL-23 as well as urine levels of IL-6 were higher in ADPKD patients compared
to the healthy controls (P < .001). There was no significant difference in the
number of T helper 17 cells between the two groups. Among different combinations
of the inflammatory markers, the serum IL-17 was the best factor in the diagnosis
of ADPKD with a sensitivity as well as specificity of 100%. CONCLUSIONS: It is
likely that T helper 17 pathway is involved in the pathogenesis of ADPKD;
therefore, it may be beneficial if such a pathway be considered in its diagnosis.
PMID- 25851289
TI - Incidence and complications of acute kidney injury following coronary artery
bypass graft: a retrospective cohort study.
AB - INTRODUCTION: Acute kidney injury (AKI) is a common complication of coronary
artery bypass graft with several serious complications. This study aimed to find
the incidence of AKI after coronary artery bypass graft and its complications
based on the Acute Kidney Injury Network (AKIN) criteria. MATERIALS AND METHODS:
This study was done on 3470 patients who had undergone isolated coronary artery
bypass graft. Acute kidney injury's incidence was based on the AKIN criteria
(only based on serum creatinine irrespective of urine output). Patients'
demographic data, in-hospital complications, and out-hospital mortality were
collected from hospital databases and compared between the patients with and
without AKI. RESULTS: Based on serum creatinine, the incidence of AKI was 27.7%
(958 patients) on the 1st postoperative day. Nine patients (0.3%) needed
hemodialysis during their hospital stay, and 31 patients (0.7%) developed
persistent kidney failure until the discharge day. The number of patients
undergoing hemodialysis was not significantly difference but persistent kidney
failure was significantly more frequent in patients with AKI (P < .001). Those
with AKI also experienced longer length of stay (P = .04) and longer length of
stay in intensive care unit (P < .001), and their mortality rate was higher in
hospital (P < .001) and during the 3-year follow-up period (P < .001).
CONCLUSIONS: Although AKI is associated with great patients' morbidity and in
hospital and long-term mortality, most of AKI episodes after coronary artery
bypass graft are mild with no need for hemodialysis, and they mostly improve
spontaneously.
PMID- 25851290
TI - Gene mutation analysis in Iranian children with nephronophthisis: a two-center
study.
AB - INTRODUCTION: Nephronophthisis is of the most commonly inherited ciliopathies
that leads to end-stage renal disease in children. The NPHP1 gene is the first
identified gene responsible for nephronophthisis and related diseases. This study
assessed mutations of the NPHP1 gene in 16 Iranian families with at least one
member presenting features of nephronophthisis. MATERIALS AND METHODS: Fifty
seven patients diagnosed with chronic kidney disease or end-stage renal disease
were referred to Imam Hossein Children Hospital, in Isfahan, Iran. The gene
analysis study was carried on 16 patients and their first-degree relatives (40
DNA samples) suspicious of having nephronophthisis. The NPHP1 deletion analysis
was performed for exons 5, 7, and 20 of the NPHP1 gene. RESULTS: The patients'
median age was 15 years. The mean and median age of the first presentation was
10.06 +/- 2.59 years and 10.5 years, respectively. A homozygous deletion was
identified in the NPHP1 gene spanning at least from exon 5 to exon 20 in two
families. High-throughput mutation analysis identified a homozygous truncating
mutation (c.1504C>T, p.R502*) in the NPHP5 in 5 families. CONCLUSIONS: By
combining NPHP1 deletion analysis with multiplex-polymerase-chain-reaction-based
high-throughput mutation analysis we could identify the molecular disease-cause
in 7 of 15 families from Iran. In 8 families, the molecular disease cause
remained unknown.
PMID- 25851291
TI - Detection of an earlier tubulopathy in diabetic nephropathy among children with
normoalbuminuria.
AB - INTRODUCTION: Diabetic nephropathy is a major cause of morbidity and mortality
among young adults with type 1 diabetes mellitus (DM). Albuminuria, the gold
standard for early diagnosis, cannot always detect early diabetic nephropathy. We
aimed at evaluating the level of urine neutrophil gelatinase-associated lipocalin
(NGAL) as a marker of tubulointerstitial damage in children and adolescents with
type 1 DM in relation to the level of albuminuria and other parameters. MATERIALS
AND METHODS: Fifty children with type 1 DM for more than 5 years were included in
this study (mean age, 13.8 +/- 4.0 years), and 18 healthy children served as
controls. Patients with overt albuminuria (> 300 mg/g creatinine) or inflammatory
states were excluded. Urine NGAL, microalbuminuria, and urine albumin-creatinine
ratio were measured in patients and controls as well as other parameters.
RESULTS: Urine NGAL was significantly higher in microalbuminuric in comparison
with normoalbuminuric patients and controls, and correlated positively with urine
albumin-creatinine ratio. A positive urine NGAL was observed in 12 of 38
normoalbuminuric patients (31.6%) compared to 9 of 12 microalbuminuric patients
(75%). A positive correlation was reported between urine NGAL and both Hemoglobin
A1c and duration of DM, but not with estimated glomerular filtration rate or
hypertension. CONCLUSIONS: Diabetic children, even some normoalbuminurics, showed
increased urine NGAL. This finding may support the hypothesis of a "tubular
phase" of diabetic disease preceding overt diabetic nephropathy, and hence, the
use of urine NGAL measurement for early evaluation of renal involvement.
PMID- 25851292
TI - Effects of lowering dialysate calcium concentration on mineral metabolism and
hemodynamic parameters in hemodialysis patients.
AB - INTRODUCTION: It has been suggested that a dialysate calcium concentration of 1.5
mmol/L is a compromise between bone protection and cardiovascular risk. This
study aimed to investigate the effect of reducing dialysate calcium concentration
to 1.5 mmol/L on mineral metabolism and hemodynamic parameters. MATERIALS AND
METHODS: Dialysate calcium concentration was changed from 1.75 mmol/L to 1.5
mmol/L for 9 months and observed the effects on mineral metabolism and dialysis
outcome parameters in 52 hemodialysis patients. RESULTS: The results at 9 months
demonstrated that postdialytic serum calcium level decreased significantly from
109 +/- 7 mg/L to 102 +/- 6 mg/L, intact parathyroid hormone (PTH) increased from
372 +/- 52 pg/mL to 606 +/- 80 pg/mL, and the oral alfacalcidol increased from
1.4 +/- 0.3 ug/w to 3.3 +/- 0.4 ug/w. In patients with low PTH levels, continuous
increase of PTH was observed. There were no significant variation in the oral
calcium carbonate dose and serum levels of alkaline phosphatase, predialytic
calcium, and pre- and postdialytic phosphorus. The ultrafiltration rate and
postdialysis systolic blood pressure were significantly lower after reducing the
dialysate calcium concentration to 1.5 mmol/L. Intradialytic hypotension and
cramps were more frequent with this dialysate calcium concentration. CONCLUSIONS:
These findings demonstrated that a decrease in dialysate calcium concentration
from 1.75 mmol/L to 1.5 mmol/L improved mineral metabolism by prevention of
postdialytic hypercalcemia and releasing oversuppression of PTH, but it was
associated with more use of oral alfacalcidol and more hemodynamic impairment.
PMID- 25851294
TI - Soluble major histocompatibility complex class I chain-related antigen A level in
chronic allograft dysfunction.
AB - INTRODUCTION: Soluble major histocompatibility complex class I chain-related
antigen A (soluble MICA) has recently been considered as an inhibitory molecule
which is shed from tumors and protects them against natural killers and some
subgroups of T cells' cytolysis. In transplantation, soluble MICA is also a
foreign antigenic molecule that can induce allospecific responses. This study
aimed to clarify its possible role in long-term kidney allograft outcome.
MATERIALS AND METHODS: Thirty patients with biopsy-proven chronic allograft
dysfunction (CAD) were pair-matched with kidney allograft recipients with 30
stable graft function. Fifteen healthy individuals were enrolled as controls.
Soluble MICA antigen and anti-HLA antibodies were measured in their serum.
RESULTS: There was no significant difference between CAD patients, stable
recipients, and healthy volunteers in frequency or titer of soluble MICA;
however, soluble MICA-positive patients were more frequent in the stable group
was than the CAD group (43.4% versus 33.3%). In addition, a high level of soluble
MICA was accompanied by enhanced humoral responses. No significant difference was
found in anti-HLA antibodies production between the CAD and stable groups.
CONCLUSIONS: Our data suggest that soluble MICA, at least in a defined range, can
protect the allograft against natural killers and T cell cytolysis; nonetheless,
its excessive amounts might stimulate immune system to exert enhanced humoral
response. In order to confirm the protective or detrimental role of soluble MICA
in kidney transplantation, conducting larger studies is necessary.
PMID- 25851293
TI - Association of programmed cell death 1 and programmed cell death 1 ligand gene
polymorphisms with delayed graft function and acute rejection in kidney allograft
recipients.
AB - INTRODUCTION: The genetic variations of co-stimulatory molecules can affect the
extent of T cell activity during T-cell mediated immunity, especially in
transplant patients. This study aimed to investigate the association of
programmed cell death 1 (PDCD1) and programmed cell death 1 ligand 1 (PDCD1LG1)
gene polymorphisms with clinical outcome of kidney transplantation. MATERIALS AND
METHODS: A total of 122 patients with a kidney transplant were included in this
retrospective study. Patients were classified into two groups of biopsy-proven
acute allograft rejection (AAR) and stable graft function (SGF) during the 5-year
follow-up period. Four single nucleotide polymorphisms in PDCD1 and PDCD1LG1 were
determined in the groups of patients as well as in 208 healthy control
individuals. RESULTS: The frequencies of PD-1.3 (+7146 G>A), PD-1.9 (+7625 C>T),
PD-L1 (8923 A>C), and PD-L1 (+6777 C>G) genotypes and alleles were not
significantly different between the AAR and SGF groups. In comparison with
healthy controls, PD-1.9 (+7625 C>T) genotype and T allele were significantly
more frequent in all of the patients and in those with SGF. Overall, 27 of 122
kidney allograft recipients experienced delayed graft function, and a higher
frequency of PD-1.9 (+7625 C>T) genotype and T allele was observed in this group
versus those without delayed graft function. Similarly, a significant high
frequency of this genotype was found among the AAR subgroup of patients with
delayed graft function. CONCLUSIONS: Our results indicate that potentially
functional genetic variation in PDCD1 can influence the outcome of kidney
transplantation.
PMID- 25851295
TI - Angiosarcoma at dialysis fistula site in a patient on continuous ambulatory
peritoneal dialysis.
AB - Arteriovenous fistula (AVF) is the best permanent access for hemodialysis.
Swelling and pain due to thrombosis and infection is common at fistula site.
Angiosarcoma is one of rare but important differential diagnosis of these signs.
We present a patient on CAPD with angiosarcoma at AVF.
PMID- 25851296
TI - Recurrent idiopathic membranous glomerulonephritis after kidney transplantation
and successful treatment with rituximab.
AB - After renal transplantation approximately forty percent of patients with
membranous glomerolunephritis (MGN) had a recurrence, most commonly during the
first year.We present two cases with recurrent MGN after kidney transplantation
who successfully treated with ritoximab.
PMID- 25851297
TI - Re: Sex differences in protective effect of recombinant human erythropoietin
against cisplatin-induced nephrotoxicity in rats.
PMID- 25851299
TI - New law on consent will overload seriously ill patients.
PMID- 25851298
TI - A randomised dose-ranging study of tiotropium Respimat(r) in children with
symptomatic asthma despite inhaled corticosteroids.
AB - BACKGROUND: A considerable number of children with asthma remain symptomatic
despite treatment with inhaled corticosteroids, resulting in significant
morbidity, reduced quality of life, increased healthcare costs and lost school
days. The aim of our study was to assess the efficacy, safety and tolerability of
once-daily tiotropium Respimat(r) 5 MUg, 2.5 MUg and 1.25 MUg add-on to medium
dose inhaled corticosteroids, with or without a leukotriene modifier, in children
aged 6-11 years with symptomatic asthma. METHODS: In this Phase II, double-blind,
placebo-controlled, incomplete-crossover, dose-ranging study, patients were
randomised to receive three of the four treatments evaluated: once-daily
tiotropium Respimat(r) 5 MUg, 2.5 MUg or 1.25 MUg or placebo Respimat(r), in the
evening during the 12-week (three * 4-week) treatment period. RESULTS: In total,
76, 74, 75 and 76 patients aged 6-11 years received tiotropium Respimat(r) 5 MUg,
2.5 MUg, 1.25 MUg and placebo Respimat(r), respectively. For the primary end
point (peak forced expiratory volume in 1 second measured within 3 hours post
dosing), the adjusted mean responses with tiotropium Respimat(r) 5 MUg (272 mL),
2.5 MUg (290 mL) and 1.25 MUg (261 mL) were significantly greater than with
placebo Respimat(r) (185 mL; p = 0.0002, p < 0.0001 and p = 0.0011,
respectively). The safety and tolerability of all doses of tiotropium Respimat(r)
were comparable with those of placebo Respimat(r), with no serious adverse events
and no events leading to discontinuation. CONCLUSIONS: Tiotropium Respimat(r) add
on to medium-dose inhaled corticosteroids, with or without a leukotriene
modifier, was efficacious in paediatric patients with symptomatic asthma and had
comparable safety and tolerability with placebo Respimat(r). TRIAL REGISTRATION:
ClinicalTrials.gov identifier NCT01383499.
PMID- 25851300
TI - Ultrasound shear wave speed measurements correlate with liver fibrosis in
children.
AB - BACKGROUND: Little published research has shown the relationship between
noninvasive US shear wave speed (SWS) measurements and degree of liver fibrosis
as established by percutaneous biopsy in children. OBJECTIVE: To assess the
relationship between liver US shear wave speed (SWS) measurements and parenchymal
fibrosis in children. MATERIALS AND METHODS: Sixty-two children (0-18 years old)
with known or suspected liver disease underwent same-day US shear wave
elastography (SWE) and clinically ordered percutaneous core needle biopsy. SWE
was performed just before the liver biopsy in the area targeted for sampling,
using an Acuson S3000 US system with a 9L4 transducer; six SWS measurements were
acquired using Virtual Touch Quantification (VTQ) and Virtual Touch IQ (VTIQ)
modes. Biopsy specimens were scored for histological fibrosis and inflammation.
Bivariate relationships were assessed using Pearson correlation, while multiple
linear regression analysis was used to establish the relationship between SWS and
predictor variables. Receiver operating characteristic (ROC) curves were created
to assess the abilities of VTQ and VTIQ to discern low vs. high liver fibrosis
(histological fibrosis scores 0-2 vs. 3-6). RESULTS: There were significant
positive correlations between liver histological fibrosis score and VTQ (n = 49)
and VTIQ (n = 48) mean shear wave speed measurements (r = 0.68 and r = 0.73; P
values <0.0001). There also were significant positive correlations between liver
histological inflammation score and VTQ and VTIQ mean shear wave speed
measurements (r = 0.47 and r = 0.44, and P = 0.0006 and P = 0.0016,
respectively). For VTQ, both histological fibrosis (P < 0.0001) and inflammation
(P = 0.04) scores were significant predictors of shear wave speed (model adjusted
R (2) = 0.49). For VTIQ, only histological fibrosis score (P < 0.0001) was a
significant predictor of shear wave speed (model adjusted R (2) = 0.56). ROC
areas under the curve were 0.84 and 0.86 for VTQ and VTIQ, respectively.
CONCLUSION: Liver US shear wave speed measurements increase with increasing
parenchymal fibrosis in children.
PMID- 25851301
TI - Diagnosis of invasive aspergillosis: recent developments and ongoing challenges.
AB - BACKGROUND: Invasive aspergillosis is an infection with high morbidity and
mortality that affects mostly immunocompromised individuals. Early identification
and targeted treatment of the infection is essential to improve survival of
affected patients. The purpose of our review is to highlight the most recent
developments in diagnosis and screening for invasive aspergillosis (IA) along
with the challenges associated with the development and validation of novel
diagnostic approaches. METHODS: Ovid MEDLINE and The Cochrane library were
searched for studies that evaluated serologic, molecular and novel methodologies
for the diagnosis of IA. RESULTS: Traditional diagnostic approaches, such as
histopathology and culture, are still considered the gold standard but lack
sufficient sensitivity. Newer serologic techniques, such as galactomannan (GM)
and beta-glucan, have already been incorporated into clinical guidelines, but
recent evidence suggests that their performance might be limited in certain
clinical settings. Molecular methods, such as the Aspergillus spp. polymerase
chain reaction (PCR), have not yet found their place in clinical practice mainly
due to lack of standardization. Novel methodologies, such as volatile organic
compound detection and lateral flow devices, have recently been developed and
promise noninvasive and rapid diagnosis of aspergillosis, while diagnostic
algorithms that incorporate both GM and PCR have proven to be effective in early
randomized trials as screening methods and can reduce the use of antifungal
agents. CONCLUSIONS: Diagnosis of IA remains challenging. Novel methodologies and
the standardization of GM and PCR might provide more reliable diagnostic tools in
the future.
PMID- 25851302
TI - Midwifery students receiving the newborn at birth: A pilot study of the impact of
structured training in neonatal resuscitation.
AB - The experience of midwifery students in receiving the newborn at birth, before
and after structured training in neonatal resuscitation: A pilot study. The
practice of receiving the newborn, including neonatal resuscitation is an
essential component of midwifery. Anecdotal evidence suggests preparation for the
task is ad hoc within midwifery curricula, leading to student's anxiety. This
paper reports impacts of neonatal resuscitation training upon levels of
knowledge, preparedness, and anxiety for midwifery students receiving the
newborn. Midwifery students participated in an online questionnaire before and
after neonatal resuscitation training. The responses collected were subjected to
descriptive analysis. Of 10 students invited, 6 completed the pre and post course
questionnaires. Knowledge of the responsibility in receiving the newborn and
instigation of resuscitation increased after attending the course. Steps to
prepare to receive the newborn and clinical signs for initial assessment remained
static. Students felt more prepared to receive the newborn after the course but
did not improve in their preparation to initiate resuscitation. Anxiety levels
remained static. Structured neonatal resuscitation training and strategies to
ensure application of skills learnt should be embedded into midwifery curricula.
Midwifery students' experience in receiving the newborn and neonatal
resuscitation is worthy of further study.
PMID- 25851303
TI - The Present and the Future of Cost-Related Non-Adherence in Medicare Part D.
PMID- 25851304
TI - The Use of Technology to Enhance Health.
PMID- 25851305
TI - In the Office and In-Between: The Role of Panel Management in Primary Care.
PMID- 25851306
TI - Inherited and environmental influences on a childhood co-occurring symptom
phenotype: Evidence from an adoption study.
AB - Risk factors for the childhood development of co-occurring internalizing and
externalizing symptoms are not well understood, despite a high prevalence and
poor clinical outcomes associated with this co-occurring phenotype. We examined
inherited and environmental risk factors for co-occurring symptoms in a sample of
children adopted at birth and their birth mothers and adoptive mothers (N = 293).
Inherited risk factors (i.e., birth mothers' processing speed and internalizing
symptoms) and environmental risk factors (i.e., adoptive mothers' processing
speed, internalizing symptoms, and uninvolved parenting) were examined as
predictors for the development of internalizing-only, externalizing-only, or co
occurring symptoms using structural equation modeling. Results suggested a unique
pattern of predictive factors for the co-occurring phenotype, with risk conferred
by adoptive mothers' uninvolved parenting, birth mothers' slower processing
speed, and the birth mothers' slower processing speed in tandem with adoptive
mothers' higher internalizing symptoms. Additional analyses indicated that when
co-occurring-symptom children were incorporated into internalizing and
externalizing symptom groups, differential risk factors for externalizing and
internalizing symptoms emerged. The findings suggest that spurious results may be
found when children with co-occurring symptoms are not examined as a unique
phenotypic group.
PMID- 25851308
TI - Prospective study of the impact of the Prosigna assay on adjuvant clinical
decision-making in unselected patients with estrogen receptor positive, human
epidermal growth factor receptor negative, node negative early-stage breast
cancer.
AB - PURPOSE: Improved understanding of risk of recurrence (ROR) is needed to reduce
cases of recurrence and more effectively treat breast cancer patients. The
purpose of this study was to examine how a gene-expression profile (GEP),
identified by Prosigna, influences physician adjuvant treatment selection for
early breast cancer (EBC) and the effects of this influence on optimizing
adjuvant treatment recommendations in clinical practice. METHODS: A prospective,
observational, multicenter study was carried out in 15 hospitals across Spain.
Participating medical oncologists completed pre-assessment, post-assessment, and
follow-up questionnaires recording their treatment recommendations and confidence
in these recommendations, before and after knowing the patient's ROR. Patients
completed questionnaires on decision-making, anxiety, and health status. RESULTS:
Between June 2013 and January 2014, 217 patients enrolled and a final 200 were
included in the study. Patients were postmenopausal, estrogen receptor positive,
human epidermal growth hormone factor negative, and node negative with either
stage 1 or stage 2 tumors. After receiving the GEP results, treatment
recommendations were changed for 40 patients (20%). The confidence of medical
oncologists in their treatment recommendations increased in 41.6% and decreased
in 6.5% of total cases. Patients reported lower anxiety after physicians made
treatment recommendations based on the GEP results (p < 0.05). CONCLUSIONS:
Though this study does not include evaluation of the impact of GEP on long-term
outcomes, it was found that GEP results influenced the treatment decisions of
medical oncologists and their confidence in adjuvant therapy selection. Patients'
anxiety about the selected adjuvant therapy decreased with use of the GEP.
PMID- 25851307
TI - Extending the amygdala in theories of threat processing.
AB - The central extended amygdala is an evolutionarily conserved set of
interconnected brain regions that play an important role in threat processing to
promote survival. Two core components of the central extended amygdala, the
central nucleus of the amygdala (Ce) and the lateral bed nucleus of the stria
terminalis (BST) are highly similar regions that serve complimentary roles by
integrating fear- and anxiety-relevant information. Survival depends on the
ability of the central extended amygdala to rapidly integrate and respond to
threats that vary in their immediacy, proximity, and characteristics. Future
studies will benefit from understanding alterations in central extended amygdala
function in relation to stress-related psychopathology.
PMID- 25851310
TI - Comparison between the ASSET EZ4 NCO and Impinger Sampling Devices for Aerosol
Sampling of 4,4'-Methylene Diphenyl Diisocyanate in Spray Foam Application.
AB - 4,4'-methylene diphenyl diisocyanate (MDI) aerosol exposure evaluation in spray
foam insulation application is known to be a challenge. Current available
techniques are either not user-friendly or are inaccurate or are not validated
for this application. A new sampler has recently been developed to address the
user-friendliness issues with other samplers: the ASSET EZ4-NCO, but the use of
this sampler in spray foam insulation applications has not been demonstrated or
validated. Because of this, the current work was undertaken to provide a
comparison of the ASSET sampler with an impinger method, considered to be the
best available method in the context of spray foam insulation, and hence the
pertinence of comparing this sampler to an impinger method, considered to be the
best available method for measuring MDI monomer and oligomers for this particular
application. Liquid chromatography coupled with tandem mass spectrometry method
for MDI monomer and oligomer analysis was implemented based on the Supelco
literature. It allows the analysis of MDI-dibutylamine (DBA) and MDI 3-ring-DBA
with a minimum reported value of 5ng ml(-1), a dynamic range of 5-140ng ml(-1),
precision <15% and accuracy >80%. This method was used to quantify MDI aerosols
collected with the ASSET sampler in an MDI spray foam environment in parallel
with the toluene/MOPIP impinger reference method. The ASSET sampler significantly
underestimated the levels of MDI monomer and oligomers when compared to the
reference method. The estimated bias was 72% (95% confidence interval [CI] 54
89%) for the monomer and 96% (95% CI 76-115%) for the oligomers. These results
demonstrate the importance of evaluating each new sampler for each isocyanate
application prior to a formal worker exposure evaluation.
PMID- 25851309
TI - Carbon Nanotube and Nanofiber Exposure Assessments: An Analysis of 14 Site
Visits.
AB - Recent evidence has suggested the potential for wide-ranging health effects that
could result from exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF).
In response, the National Institute for Occupational Safety and Health (NIOSH)
set a recommended exposure limit (REL) for CNT and CNF: 1 ug m(-3) as an 8-h time
weighted average (TWA) of elemental carbon (EC) for the respirable size fraction.
The purpose of this study was to conduct an industrywide exposure assessment
among US CNT and CNF manufacturers and users. Fourteen total sites were visited
to assess exposures to CNT (13 sites) and CNF (1 site). Personal breathing zone
(PBZ) and area samples were collected for both the inhalable and respirable mass
concentration of EC, using NIOSH Method 5040. Inhalable PBZ samples were
collected at nine sites while at the remaining five sites both respirable and
inhalable PBZ samples were collected side-by-side. Transmission electron
microscopy (TEM) PBZ and area samples were also collected at the inhalable size
fraction and analyzed to quantify and size CNT and CNF agglomerate and fibrous
exposures. Respirable EC PBZ concentrations ranged from 0.02 to 2.94 ug m(-3)
with a geometric mean (GM) of 0.34 ug m(-3) and an 8-h TWA of 0.16 ug m(-3). PBZ
samples at the inhalable size fraction for EC ranged from 0.01 to 79.57 ug m(-3)
with a GM of 1.21 ug m(-3). PBZ samples analyzed by TEM showed concentrations
ranging from 0.0001 to 1.613 CNT or CNF-structures per cm(3) with a GM of 0.008
and an 8-h TWA concentration of 0.003. The most common CNT structure sizes were
found to be larger agglomerates in the 2-5 um range as well as agglomerates >5
um. A statistically significant correlation was observed between the inhalable
samples for the mass of EC and structure counts by TEM (Spearman rho = 0.39, P <
0.0001). Overall, EC PBZ and area TWA samples were below the NIOSH REL (96% were
<1 MUg m(-3) at the respirable size fraction), while 30% of the inhalable PBZ EC
samples were found to be >1 MUg m(-3). Until more information is known about
health effects associated with larger agglomerates, it seems prudent to assess
worker exposure to airborne CNT and CNF materials by monitoring EC at both the
respirable and inhalable size fractions. Concurrent TEM samples should be
collected to confirm the presence of CNT and CNF.
PMID- 25851311
TI - Hypericum perforatum Reduces Paracetamol-Induced Hepatotoxicity and Lethality in
Mice by Modulating Inflammation and Oxidative Stress.
AB - Hypericum perforatum is a medicinal plant with anti-inflammatory and antioxidant
properties, which is commercially available for therapeutic use in Brazil. Herein
the effect of H. perforatum extract on paracetamol (acetaminophen)-induced
hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice
were investigated. HPLC analysis demonstrated the presence of rutin, quercetin,
hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol
(0.15-3.0 g/kg, p.o.) induced dose-dependent mortality. The sub-maximal lethal
dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study.
H. perforatum (30-300 mg/kg, i.p.) dose-dependently reduced paracetamol-induced
lethality. Paracetamol-induced increase in plasma aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) concentrations, and hepatic
myeloperoxidase activity, IL-1beta, TNF-alpha, and IFN-gamma concentrations as
well as decreased reduced glutathione (GSH) concentrations and capacity to reduce
2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate radical cation; ABTS(+) ) were
inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum
protects mice against paracetamol-induced lethality and liver damage. This effect
seems to be related to the reduction of paracetamol-induced cytokine production,
neutrophil recruitment, and oxidative stress.
PMID- 25851312
TI - Simplified Citrate Anticoagulation for CRRT Without Calcium Replacement.
AB - Since 2012, citrate anticoagulation is the recommended anticoagulation strategy
for continuous renal replacement therapy (CRRT). The main drawback using citrate
as anticoagulant compared with heparin is the need for calcium replacement and
the rigorous control of calcium levels. This study investigated the possibility
to achieve anticoagulation while eliminating the need for calcium replacement.
This was successfully achieved by including citrate and calcium in all CRRT
solutions. Thereby the total calcium concentration was kept constant throughout
the extracorporeal circuit, whereas the ionized calcium was kept at low levels
enough to avoid clotting. Being a completely new concept, only five patients with
acute renal failure were included in a short, prospective, intensely supervised
nonrandomized pilot study. Systemic electrolyte levels and acid-base parameters
were stable and remained within physiologic levels. Ionized calcium levels
declined slightly initially but stabilized at 1.1 mmol/L. Plasma citrate
concentrations stabilized at approximately 0.6 mmol/L. All postfilter ionized
calcium levels were <0.5 mmol/L, that is, an anticoagulation effect was reached.
All filter pressures were normal indicating no clotting problems, and no visible
clotting was observed. No calcium replacement was needed. This pilot study
suggests that it is possible to perform regional citrate anticoagulation without
the need for separate calcium infusion during CRRT.
PMID- 25851313
TI - Influence of Sterilization and Storage Period on Elution of Polyvinylpyrrolidone
from Wet-Type Polysulfone Membrane Dialyzers.
AB - The objectives of this study were to investigate the influence of the
sterilization and storage period on elution of polyvinylpyrrolidone (PVP) from
wet-type polysulfone (PSu) membrane dialyzers. APS-15SA (APS) dialyzers
sterilized by gamma-radiation and RENAK PS-1.6 (RENAK) dialyzers sterilized by
autoclaving were compared in this study. Each dialyzer was washed with
physiological saline and the amount of PVP eluted from the PSu membrane was
measured. Then, experimental use of each dialyzer was performed by circulating
physiological saline for 4 hours, after which the PVP eluted from the PSu
membrane was measured. As the results, the amount of PVP eluted by washing was
positively correlated with the storage period for both dialyzers (APS: rs =
0.958; RENAK: rs = 0.952). In the experimental circuit, the amount of PVP eluted
from the RENAK dialyzer was positively correlated with the storage period (rs =
0.810), whereas the amount of PVP eluted from the APS dialyzer was negatively
correlated with the storage period (rs = -0.833). We found that the amount of PVP
eluted from PSu membrane is quite different by the sterilization and storage
period of dialyzers.
PMID- 25851314
TI - Development of a Double-Lumen Cannula for a Percutaneous RVAD.
AB - The objectives were to design/fabricate a double-lumen cannula (DLC) for a
percutaneous right ventricular assist device (pRVAD) and to test the
feasibility/performance of this pRVAD system. A 27 Fr DLC prototype was made and
tested in six adult sheep. The pRVAD DLC was inserted into the right jugular
vein; advanced through the superior vena cava, the right atrium (RA), the right
ventricle (RV); ending in the pulmonary artery (PA). A CentriMag pump and
optional gas exchanger were connected to the DLC. Blood was withdrawn from RA,
pumped through gas exchanger, and perfused PA. Maximal pumping flow was
maintained for 2 hours. The pRVAD DLC was successfully deployed in all six sheep.
In first three sheep, maximal average pumping flow was less than 3 L/min because
the DLC was advanced too far with drainage opening against RA side wall. In last
three sheep with well-positioned DLC, average maximal flow was more than 3.5
L/min. The gas exchanger provided up to 230 ml/min CO2 removal and 174 ml/min O2
transfer. Our DLC-based pRVAD system is feasible for percutaneous right heart and
respiratory assistance through a single cannulation. The pRVAD DLC can be easily
placed prophylactically during left ventricular assist device implantation and
removed as needed without additional open chest procedures.
PMID- 25851315
TI - Successful Porcine Renal Transplantation After 60 Minutes of Donor Warm Ischemia:
Extracorporeal Perfusion and Thrombolytics.
AB - Donation from uncontrolled circulatory determination of death donors (uDCD) is
impractical in United States because of the time needed to organize procurement
before irreversible organ damage. Salvaging organs after prolonged warm ischemic
time (WIT) may address this limitation. We evaluated the combination of
extracorporeal support (ECS) and thrombolytics in a porcine uDCD renal transplant
model. Nonanticoagulated uDCD sustained 60 min of WIT, and two groups were
studied. Rapid recovery (RR)-uDCD renal grafts procured using the standard quick
topical cooling and renal flush, and ECS-assisted donation (E-uDCD), 4 hr ECS
plus thrombolytics for in situ perfusion before procurement. All kidneys were
flushed and cold stored, followed by transplantation into healthy nephrectomized
recipients without immunosuppression. Delayed graft function (DGF) was defined as
creatinine more than 5.0 mg/dl on any postoperative day. Twelve kidneys in E-uDCD
and 6 in RR-uDCD group were transplanted. All 12 E-uDCD recipients had urine
production and adequate function in the first 48 hr, but two grafts (16.7%) had
DGF at 96 hr. All six recipients from RR-uDCD group had DGF at 48 hr and were
killed. Creatinine and blood urea nitrogen (BUN) levels were significantly lower
in E-uDCD compared with RR-uDCD group at 24 hr (2.9 +/- 0.7 mg/dl vs. 5.2 +/- 0.9
mg/dl) and 48 hr (3.2 +/- 0.9 mg/dl vs. 7.2 +/- 1.0 mg/dl); BUN levels at 24 and
48 hr were 28.3 +/- 6.7 mg/dl vs. 39.5 +/- 7.5 mg/dl and 23.9 +/- 5.0 mg/dl vs.
46 +/- 12.9 mg/dl, respectively. Thrombolytics plus ECS precondition organs in
situ yielding functional kidneys in a porcine model of uDCD with 60 min of WIT.
This procurement method addresses logistical limitations for uDCD use in the
United States and could have a major impact on the organ donor pool.
PMID- 25851316
TI - The image of submitral aneurysm with multiple fistulas.
PMID- 25851317
TI - Antenatal diagnosis of idiopathic arterial calcification with hydrops fetalis.
PMID- 25851318
TI - Cardiac CT angiography for device surveillance after endovascular left atrial
appendage closure.
AB - AIMS: Left atrial appendage (LAA) device imaging after endovascular closure is
important to assess for device thrombus, residual leak, positioning, surrounding
structures, and pericardial effusion. Cardiac CT angiography (CCTA) is well
suited to assess these non-invasively. METHODS AND RESULTS: We report our
consecutive series of non-valvular atrial fibrillation patients who underwent
CCTA post-LAA closure with Amplatzer Cardiac Plug (ACP), Amulet (second
generation ACP), or WATCHMAN devices. Patients underwent CCTA typically 1-6
months post-implantation. Prospective cardiac-gated CCTA was performed with
Toshiba 320-detector or Siemens 2nd generation 128-slice dual-source scanners,
and images interpreted with VitreaWorkstationTM. GFR <30 mL/min/1.73 m(2) was an
exclusion. We assessed for device thrombus, residual LAA leak, device
embolization, position, pericardial effusion, optimal implantation, and device
lobe dimensions. Forty-five patients underwent CCTA at median 97 days post-LAA
closure (18 ACP, 9 Amulet, 18 WATCHMAN). Average age was 75.5 +/- 8.9 years, mean
CHADS2 score 3.1 +/- 1.3, and CHADS-VASc score 4.9 +/- 1.6. All had
contraindications to oral anticoagulation. Post-procedure, 41 (91.1%) were
discharged on DAPT. There was one device embolization (ACP, successfully
retrieved percutaneously) and one thrombus (WATCHMAN, resolved with 3 months of
warfarin). There were two pericardial effusions, both pre-existing and not
requiring intervention. Residual leak (patency) was seen in 28/44 (63.6%), and
the mechanisms of leak were readily identified by CCTA (off-axis device, gaps at
orifice, or fabric leak). Mean follow-up was 1.2 +/- 1.1year, with no death,
stroke, or systemic embolism. CONCLUSION: CCTA appears to be a feasible
alternative to transoesophageal echocardiography for post-LAA device surveillance
to evaluate for device thrombus, residual leak, embolization, position, and
pericardial effusion.
PMID- 25851319
TI - Temporal changes in the use and results of exercise echocardiography.
AB - AIMS: Limited data are available regarding changes over time in referral patterns
and outcomes of non-invasive cardiac stress testing. Our aim was to evaluate the
temporal changes in the use and results of exercise echocardiography in our area
of reference. METHODS AND RESULTS: A total of 12 339 patients referred to our
unit for exercise echocardiography between 1997 and 2012 were included. We
divided the 16-year period into four quadrennia and evaluated the changes in
clinical data, results of the tests, referrals for invasive management and
outcomes. We observed a gradual decrease in the frequency of detection of
myocardial ischaemia from 35.3% in1997-2000 to 25.4% in 2009-12 (P < 0.001).
There was also a progressive increase in the prevalence of cardiovascular risk
factors and in the frequency of non-ischaemic chest pain and dyspnoea, while the
proportion of patients with prior myocardial infarction and non-interpretable
electrocardiograms declined. The rate of referral to coronary angiography within
6 months decreased from 24.8% in 1997-2000 to 19.6% in 2009-12 (P < 0.001), but
the rate of coronary revascularization remained almost unchanged (13.1 to 11.7%,
P for the trend = 0.16). We also observed a progressive decrease in the 1-year
mortality rate from 3.4 to 1% (P < 0.001). CONCLUSION: Over a 16-year period,
there was a gradual decrease in the frequency of myocardial ischaemia among
patients referred to our unit for exercise echocardiography, which was parallel
to changes in their clinical profile. However, this was not accompanied by a
significant reduction in the rate of coronary revascularization.
PMID- 25851320
TI - Prosthetic valve endocarditis: multiple complications in one patient.
PMID- 25851321
TI - Aortic forward flow in aortic atresia via ventriculo-coronary arterial
connections.
PMID- 25851322
TI - Atrioesophageal fistula and pneumocephalus after pulmonary vein isolation.
PMID- 25851323
TI - Factors associated with B-lines after exposure to hypobaric hypoxia.
AB - AIMS: Increased extravascular lung water (EVLW) is seen as B-lines on chest
ultrasonography. In lowlanders ascending to altitude the time course,
relationship with the patient's clinical status and factors affecting B-lines are
still unclear. The aim was to monitor B-lines, clinical status and N-terminal B
type natriuretic peptide (NT-proBNP) during exposure to high altitude. METHODS
AND RESULTS: Chest ultrasonography, blood samples, cardiovascular parameters, and
signs and symptoms of high altitude pulmonary oedema (HAPE) were prospectively
assessed in 19 participants at baseline and after ascent to 3830 m (9, 24, 48, 72
h, and 8 days) by blinded investigators. Potential confounding factors (e.g.
altitude variations, physical effort) were minimized. Generalized estimating
equations were used to analyse factors associated with B-lines. B-lines changed
with exposure to altitude (P = 0.006) in a parabolic-like pattern within the
first 72 h; 10 of 18 participants (55.6%) had >5 B-lines at 24 h. B-lines were
correlated with the number of signs and symptoms (partial coefficient = 0.372, P
= 0.001). B-lines were associated with time (P = 0.038), sex (P = 0.013), and
SpO2 (P = 0.042), but not with NT-proBNP (P = 0.546). The participant with a
clinical diagnosis of HAPE had 23 B-lines. CONCLUSION: B-lines during exposure to
altitude seem to reflect the individual response to hypobaric hypoxia and
represent clinically relevant alterations at high altitude, also in patients with
HAPE. Similar to previous studies, our results support a non-cardiogenic
aetiology of B-lines.
PMID- 25851324
TI - Basal hyperaemia is the primary abnormality of perfusion in Takotsubo
cardiomyopathy: a quantitative cardiac perfusion positron emission tomography
study.
AB - AIMS: Takotsubo cardiomyopathy (TTC) is characterized by acute completely
reversible regional left ventricle (LV) akinesia and decreased tracer uptake in
the akinetic region on semi-quantitative perfusion imaging. The latter may be due
to normoperfusion of the akinetic mid/apical area and basal hyperperfusion. Our
aim was to examine abnormalities of perfusion in TTC, and we hypothesized that
basal hyperperfusion is the primary perfusion abnormality in the acute state.
METHOD AND RESULTS: Twenty-five patients were diagnosed with TTC due to (i) acute
onset of symptoms, (ii) typical apical ballooning, (iii) absence of significant
coronary disease, and (iv) complete remission on 4-month follow-up. The patients
underwent coronary angiography (CAG), echocardiography, cardiac magnetic
resonance imaging (CMR), and (13)NH3/(82)Rb positron emission tomography (PET) in
the acute state and-except CAG-on follow-up. Patients initially had severe heart
failure, mid/apical oedema but no infarction, and a rise in cardiac biomarkers.
On initial perfusion PET imaging, eight patients appeared to have normal, whereas
17 patients had impaired LV perfusion. In the latter, flow in the basal region
was increased in the acute state (1.5 +/- 0.1 vs. 1.2 +/- 0.1 mL/g/minRPP
corrected, P < 0.01), whereas midventricular (1.7 +/- 0.1 vs. 1.6 +/- 0.1
mL/g/minRPP-corrected, P = 0.21) and apical (1.4 +/- 0.1 vs. 1.5 +/- 0.1
mL/g/minRPP-corrected, P = 0.36) flow was unchanged between acute and follow-up,
and within normal range. CONCLUSION: Our results suggest an abnormal LV perfusion
distribution in the acute state of TTC with basal hyperperfusion and a
normoperfused akinetic region. The proportion of patients without visualized
perfusion abnormalities in the acute state may represent a subgroup with fast
remission.
PMID- 25851326
TI - Cardiovascular magnetic resonance of a hiatus hernia causing positional cardiac
compression.
PMID- 25851325
TI - Right ventricular echocardiographic indices predict poor outcomes in infants with
persistent pulmonary hypertension of the newborn.
AB - AIMS: Infants with persistent pulmonary hypertension of the newborn (PPHN) have
elevated pulmonary vascular resistance that can lead to right ventricular (RV)
failure and death. Clinicians must decide which infants will fail conventional
therapy and require transfer to extra corporeal membrane oxygenation (ECMO)
centres, but accurate echocardiographic predictors have not been identified. We
assessed echocardiographic measurements of RV pressure and function in predicting
progression to death or ECMO in infants with PPHN. METHODS AND RESULTS:
Echocardiograms for infants >=35-week gestation with a clinical diagnosis of PPHN
were retrospectively reviewed. Traditional and strain echocardiographic measures
were compared for those with or without the primary outcome of
ECMO/cardiovascular death. Receiver operator curves identified cut points for
measures that were significantly different. Of the 86 subjects analysed, 25 (29%)
of the patients had the primary outcome of ECMO/death. The ECMO/death group had
diminished tricuspid annular plane systolic excursion (TAPSE; P = 0.002) and RV
global longitudinal peak strain (GLPS; P = 0.03), a predominant right-to-left
shunt across the patent ductus arteriosus (PDA; P = 0.05), and an elevated
oxygenation index (OI; P < 0.001). Sensitivity/specificity for TAPSE <4 mm was 56
and 85%, and for GLPS greater than or equal to -9% was 52 and 77%. CONCLUSION:
TAPSE, GLPS, and right-to-left PDA shunting were associated with progression to
death/ECMO. RV free wall strain was not associated with the outcome, suggesting
that diminished global strain better reflects clinical outcomes in this group.
These thresholds may assist in the decision-making to transfer high-risk infants
to ECMO centres.
PMID- 25851327
TI - Simultaneous huge apical left ventricular diverticulum and a narrow annulus over
the narrow neck.
PMID- 25851328
TI - Spontaneous arteriovenous fistula of left internal iliac artery aneurysm.
PMID- 25851329
TI - Non-invasive myocardial work index identifies acute coronary occlusion in
patients with non-ST-segment elevation-acute coronary syndrome.
AB - AIMS: Acute coronary artery occlusion (ACO) occurs in ~30% of patients with non
ST-segment elevation-acute coronary syndrome (NSTE-ACS). We investigated the
ability of a regional non-invasive myocardial work index (MWI) to identify ACO.
METHODS AND RESULTS: Segmental strain analysis was performed before coronary
angiography in 126 patients with NSTE-ACS. Left ventricular (LV) pressure was
estimated non-invasively using a standard waveform fitted to valvular events and
scaled to systolic blood pressure. MWI was calculated as the area of the LV
pressure-strain loop. Empirical cut-off values were set to identify segmental
systolic dysfunction for MWI (<1700 mmHg %) and strain (more than -14%). The
number of dysfunctional segments was used in ROC analysis to identify ACO. The
presence of >=4 adjacent dysfunctional segments assessed by MWI was significantly
better than both global strain and ejection fraction at detecting the occurrence
of ACO (P < 0.05). Regional MWI had a higher sensitivity (81 vs. 78%) and
especially specificity (82 vs. 65%) compared with regional strain. Logistic
regression demonstrated that elevated systolic blood pressure significantly
decreased the probability of actual ACO in a patient with an area of impaired
regional strain. CONCLUSION: The presence of a region of reduced MWI in patients
with NSTE-ACS identified patients with ACO and was superior to all other
parameters. The regional MWI was able to account for the influence of systolic
blood pressure on regional contraction. We therefore propose that MWI may serve
as an important clinical tool for selecting patients in need of prompt invasive
treatment.
PMID- 25851330
TI - Bi-ventricular contractile reserve offers an incremental prognostic value for
patients with dilated cardiomyopathy.
AB - AIMS: Right ventricular (RV) as well as left ventricular (LV) function has been
recognized as an important prognostic factor for heart failure patients. Our
objective was thus to investigate the prognostic significance of combined
assessment of bi-ventricular functional reserve for patients with dilated
cardiomyopathy (DCM). METHODS AND RESULTS: We studied 104 DCM patients with
ejection fractions (EF) of 32 +/- 9%, and speckle-tracking echocardiography was
used to assess both RV and LV contractile reserve under dobutamine stress (20
ug/kg/min). RV contractile function was measured as peak global longitudinal
strain (GLS) from the RV free wall (RV-free), and LV function as global
circumferential strain (GCS) and GLS, respectively. Event-free survival was then
tracked for 17 months. Twenty-one patients (20%) developed cardiovascular events.
A multivariate Cox proportional-hazards analysis revealed that the baseline EF,
E/A, and the relative change in EF (DeltaEF), in GCS (DeltaGCS), and in RV-free
(DeltaRV-free) during dobutamine stress were the independent predictors of
cardiovascular events (P < 0.001, <0.05, <0.01, <0.05, and <0.01, respectively).
A Cox model based on baseline clinical and echocardiographic variables (chi(2) =
23.6) was improved by the addition of LV contractile reserve parameters (plus
DeltaGCS and DeltaEF) (chi(2) = 49.1; P < 0.001) and further improved by adding
RV contractile reserve (plus DeltaRV-free) (chi(2) = 60.3, P < 0.001).
CONCLUSION: Assessment of RV contractile reserve during dobutamine stress offers
a significantly better prognostic value for patients with DCM. Bi-ventricular
contractile reserve may be required for a favourable outcome, so that estimation
of RV contractile reserve should be considered part of a comprehensive functional
assessment of these patients.
PMID- 25851331
TI - Influence of case-based e-learning on students' performance in point-of-care
ultrasound courses: a randomized trial.
AB - BACKGROUND: Theoretical knowledge, visual perception, and sensorimotor skills are
key elements in ultrasound education. Classroom-based presentations are used
routinely to teach theoretical knowledge, whereas visual perception and
sensorimotor skills typically require hands-on training (HT). We aimed to compare
the effect of classroom-based lectures versus a case-based e-learning (based on
clinical cases only) on the hands-on performance of trainees during an emergency
ultrasound course. PARTICIPANTS AND METHODS: This is a randomized, controlled,
parallel-group study. Sixty-two medical students were randomized into two groups
[group 1 (G1) and group 2 (G2)]. G1 (n=29) was subjected to a precourse e
learning, based on 14 short screencasts (each 5 min), an on-site discussion (60
min), and a standardized HT session on the day of the course. G2 (n=31) received
classroom-based presentations on the day of the course before an identical HT
session. Both groups completed a multiple-choice (MC) pretest (test A), a
practical postcourse test (objective structured clinical exam), and MC tests
directly after the HT (test B) and 1 day after the course (test C). The Mann
Whitney U-test was used for statistical analysis. RESULTS: G1 performed markedly
better in test A (median 84.2, 25%; 75% percentile: 68.5; 92.2) compared with G2
(65.8; 53.8; 80.4), who had not participated in case-based e-learning (P=0.0009).
No differences were found in the objective structured clinical exam, test B, and
test C. CONCLUSION: e-learning exclusively based on clinical cases is an
effective method of education in preparation for HT sessions and can reduce
attendance time in ultrasound courses.
PMID- 25851332
TI - A retrospective review of sudden onset severe headache and subarachnoid
haemorrhage on the clinical decision unit: looking for a needle in a haystack?
AB - INTRODUCTION: Patients commonly present to the Emergency Department with sudden
onset acute severe headache, but exclusion of significant secondary causes,
particularly subarachnoid haemorrhage (SAH), is vital. The misdiagnosis of SAH is
most likely in patients with a normal neurological examination, and the
consequences can be disastrous. A noncontrast computed tomography (CT) brain scan
is the initial investigation of choice, and most would recommend that, if
negative, this be followed by a lumbar puncture (LP) and cerebrospinal fluid
(CSF) analysis. Many hospitals in the UK have developed Clinical Decision Unit
(CDU) pathways to provide a standardized approach to the investigation and
management of neurologically normal patients with headache suggestive of SAH.
AIMS: The aims of this study were to describe the prevalence of SAH and to
evaluate the performance of CT and LP in a CDU population with sudden onset acute
severe headache. METHODS: A retrospective review of neurologically pristine
patients admitted to a CDU pathway for exclusion of SAH was conducted. Structured
case notes were reviewed; patient demographics, investigation results and
clinical outcomes were recorded in each case. RESULTS: The overall prevalence of
SAH in this population was 14/517 (2.7%). A noncontrast CT of the brain had a
negative predictive value of 99.8%, reducing the post-test probability of having
an angiogram-positive SAH detected by LP and CSF analysis to 0.21% (95%
confidence interval 0.04-0.36%). CONCLUSION: The management of neurologically
pristine patients with sudden onset severe headache on a CDU pathway is feasible.
In light of the low prevalence of SAH in this population, the decision to follow
a negative CT with an LP in all cases needs careful consideration, as CSF results
may only rarely confer therapeutic benefit to patients suspected of SAH.
PMID- 25851333
TI - A combination of clinical parameters and blood-gas analysis identifies patients
at risk of transfer to intensive care upon arrival to the Emergency Department.
AB - OBJECTIVES: Identifying patients at risk of transfer to the ICU upon arrival to
the Emergency Department (ED) might direct early therapy and optimize transfers.
However, among the many ED patients, it is difficult to pinpoint the few who
insidiously deteriorate to an ICU-requiring level. The aim of this study was to
identify predictors in background information, vital values and blood-gas
analysis for transfer to ICU 3-36 h after arrival among nontrauma ED patients.
METHODS: A case-control study of 10 007 acute adult patients admitted to ED
within 1 year was carried out. The case group consisted of all ICU transfers 3-36
h after arrival who underwent blood-gas analysis and a similar control group not
transferred to the ICU. Blood pressure, respiratory frequency, pulse rate,
peripheral oxygen saturation and temperature, triage, height, weight, Glasgow
Coma Score, drugs, alcohol, tobacco, age, sex, Charlson score and blood-gas
results were analysed. RESULTS: A total of 49 medical and 33 surgical patients
were transferred to the ICU. For medical cases, 2.3 and surgical cases 3.7
controls were included. For medical patients, low systolic blood pressure [odds
ratio (OR) 14.4], elevated heart rate (OR 3.9), severe acidosis (OR 5.1) and
hypercapnia (OR 8.4) and for surgical patients age 60-79 years (OR 6.3), low
diastolic blood pressure (OR 2.7) and severe acidosis (OR 15.3) were associated
significantly with later transfer to the ICU. CONCLUSION: The predictors
identified could be used as part of ED triage to identify high-risk patients for
ICU. These findings should be examined in a well-designed prospective cohort
study.
PMID- 25851334
TI - Contact sensitisation in patients with chronic leg ulcers.
AB - The aim of our study is to identify the allergens in patients with leg ulcers who
have contact dermatitis surrounding the skin of the ulcer and compare them with a
control group consisting of patients with lower extremity contact dermatitis. A
total of 40 patients with chronic leg ulcers (CLU) and contact dermatitis around
the skin of ulcer were included in the study. As a control group, 20 patients
with contact dermatitis of lower extremity without leg ulcers were included. The
patient and control groups were patch tested with 37 allergens of the European
Standard Series. Of the 40 patients, 31 (77.5%) had positivity to one or more
allergens, and 10 (50%) of the control group patients had positivity to one or
more allergens. The number of patients who had positivity to at least one
allergen was significantly higher in the patient group (P < 0.05). Positivity to
the balsam of Peru and benzocaine was significantly higher in the patient group
than that in the control group (P < 0.05). Contact sensitisation to benzocaine
and balsam of Peru was found to be associated with the presence of CLU. The
efficacy of therapy in patients with leg ulcers might be increased by avoiding
these allergens.
PMID- 25851335
TI - Systematizing cultural awareness: Toward a model for modification of trauma
therapy and an application in Turkey.
AB - A cross-cultural team including a U.S.-trained clinical cross-cultural
psychologist and two Turkish psychiatrists conducted research on a set of five
trauma treatment psychotherapy groups for adult women survivors of sexual abuse
in Ankara, Turkey. Based upon observational comparisons between trauma treatment
groups in U.S. and Turkish settings, the team developed an approach to assist in
adaptation of treatment methods from one cultural setting to another. This is a
preliminary effort to develop a conceptual tool to focus the attention of
therapists on salient dimensions of culture that may influence the psychotherapy
process. This article describes six possible dimensions: (a)
relational/individual self; (b) situationalism/universalism; (c) high/low power
differential; (cc) high/low gender differential; (d) internal/external control;
(e) emotional expressivity/containment; and (f) short-term/long-term time
orientation. Comparative cultural examples from trauma psychotherapy group field
notes illustrate the use of the tool.
PMID- 25851336
TI - Effects of a culturally sensitive assessment on symptom profiles in native Dutch
and Moroccan patients with a first psychosis referral.
AB - Previous studies have reported a higher incidence of psychosis in Moroccan
immigrants in the Netherlands than among native-born residents. However, this
disparity was substantially attenuated when cultural differences in symptom
presentation were taken into account. To better understand the impact of
different diagnostic procedures on incidence rates, we examined the effects of
the use of a culturally sensitive diagnostic interview, compared to a standard
semi-structured diagnostic interview, on symptom profiles among Moroccan
immigrant and native Dutch patients in the Netherlands. A total of 26 Dutch and
26 Moroccan patients referred with a possible first psychosis diagnosis were
interviewed twice: once with the standard version and once with a culturally
adapted version of the Comprehensive Assessment of Symptoms and History
questionnaire (CASH and CASH-CS, respectively). Among native Dutch patients,
symptoms profiles based on CASH and CASH-CS interviews were very similar. By
contrast, among Moroccan immigrant patients, symptom profiles based on CASH and
CASH-CS interviews differed substantially, with more mania symptoms (+30%; p <
.05) and fewer delusions (-31%; p < .05) reported when using the CASH-CS. These
results suggest that the over-diagnosis of schizophrenia in Moroccan immigrants
with a first psychosis referral may be related to a tendency to under-detect mood
symptoms and over-detect positive psychotic symptoms when a standard diagnostic
procedure is used. This bias may be corrected, at least in part, by the use of a
culturally sensitive interview instrument such as the CASH- CS.
PMID- 25851338
TI - Genetic Variations in Glutathione Pathway Genes Predict Cancer Recurrence in
Patients Treated with Transurethral Resection and Bacillus Calmette-Guerin
Instillation for Non-muscle Invasive Bladder Cancer.
AB - BACKGROUND: Glutathione (GSH) is an important molecule involved in cell
detoxification and antioxidation and may affect cancer development or outcome. We
hypothesized that genetic variation in the GSH pathway might influence the
clinical outcome of patients who have non-muscle invasive bladder cancer (NMIBC).
METHODS: A total of 114 single nucleotide polymorphisms (SNPs) in 21 GSH pathway
genes were genotyped in 414 NMIBC patients treated with transurethral resection
alone (TUR) and both TUR and intravesical bacillus Calmette-Guerin instillation
(BCG) therapy. The effect of each SNP on time to recurrence was estimated using
the multivariate Cox proportional hazards model. Cumulative effect and survival
tree analyses were performed to determine the joint effects of unfavorable
genotypes and gene-gene interactions on bladder cancer prognosis. RESULTS: Seven
SNPs showed significant associations with cancer recurrence in the TUR group and
15 SNPs showed significant associations with recurrence in the BCG group. The
most significant SNP in the TUR group was rs3746162 in GPX4, whose variant
genotype conferred a 5.4-fold increased risk of recurrence compared with wild
type (hazard ratio [HR] = 5.43, 95 % confidence interval [CI] = 2.19-13.46),
whereas the most significant SNP in the BCG group was rs7265992 in GSS (HR 3.43,
95 % CI 1.56-7.56). The risk of recurrence increased with the number of
unfavorable genotypes in both groups. Within treatment group, stratified analyses
by tumor grade also indicated predictive variants. CONCLUSIONS: Genetic variants
in GSH pathway may influence cancer recurrence in NMIBC patients receiving
curative treatment.
PMID- 25851339
TI - Preoperative Chronic Kidney Disease Status is an Independent Prognostic Factor in
Patients with Renal Cell Carcinoma.
AB - PURPOSE: Preoperative chronic kidney disease (CKD) status may affect disease
outcomes in patients with renal cell carcinoma (RCC). This study evaluated the
influence of preoperative CKD status on clinicopathological features and
prognosis in patients with RCC. METHODS: Between 1999 and 2011, a total of 1855
patients underwent radical nephrectomy at various centers throughout Korea. Of
these patients, 1655 had an estimated glomerular filtration rate (eGFR) >=60
ml/min/1.73 m(2) (non-CKD group) and 200 patients had an eGFR >=30 but <60
ml/min/1.73 m(2) (CKD group). To reduce the effects of selection bias and
potential confounding factors, 600 patients in the non-CKD group were selected by
propensity-score matching. RESULTS: The median age of all patients was 57.3 years
(range 20-94 years) and the median follow-up was 35.0 months (range 1-154
months). Comparisons of the propensity-score-matched cohorts showed that T and N
stages were more advanced and tumor size was larger in the CKD group than in the
non-CKD group (p < 0.05 each). Kaplan-Meier analyses showed that recurrence-free
survival, cancer-specific survival (CSS), and overall survival (OS) were
significantly lower in the CKD group (p < 0.01 each). Multivariate regression
analysis showed that preoperative CKD status was an independent predictor of CSS
and OS in patients with RCC (p < 0.05 each). CONCLUSIONS: Preoperative CKD may be
associated with more aggressive features and poorer prognosis in patients with
RCC. RCC patients with preoperative CKD should be carefully and frequently
followed-up after nephrectomy.
PMID- 25851340
TI - Erratum to: Outcomes of Modified Harrington Reconstructions for Nonprimary
Periacetabular Tumors: An Effective and Inexpensive Technique.
PMID- 25851341
TI - The Effect of Thyroiditis on the Yield of Central Compartment Lymph Nodes in
Patients with Papillary Thyroid Cancer.
AB - BACKGROUND: In patients who have undergone thyroidectomy and central compartment
neck dissection (CCND) for papillary thyroid cancer (PTC), visualization of
enlarged lymph nodes may lead to more extensive CCND. This study sought to
determine the effect of patient age and the presence of thyroiditis on the number
of malignant and total lymph nodes resected in patients who underwent CCND for
PTC. METHODS: This retrospective review examined a prospective database of
patients who underwent total thyroidectomy and CCND for PTC between April 2009
and June 2013 and had thyroiditis on the final pathology. The patients were
categorized into age groups by decade (18-29, 30-39, 40-49, 50-59, and >=60
years) and compared with a control group of patients matched by age, gender, and
tumor size. RESULTS: Of 74 patients with thyroiditis, 64 (87 %) were women. The
median age of the patients was 47.5 years (range 18.2-72.0 years). The patients
with thyroiditis had more lymph nodes resected than those without thyroiditis
(median 11 vs 7; p < 0.01). However, these patients had fewer malignant lymph
nodes (median 0 vs 1.5; p = 0.06), resulting in a lower lymph node ratio (0 vs
0.18; p = 0.02) for the entire cohort, but particularly for the youngest (18-29
years) and oldest (>=60 years) age groups. CONCLUSIONS: Patients with thyroiditis
and PTC who underwent CCND had more lymph nodes resected but a had lower
proportion of metastatic lymph nodes than those without thyroiditis. Given the
relatively low yield of malignant cervical lymphadenopathy, a more judicious
approach to CCND might be considered, particularly for the youngest and oldest
patients with PTC and thyroiditis.
PMID- 25851342
TI - Preferential occupancy of strontium in the hydroxyapatite lattice in biphasic
mixtures formed from non-stoichiometric calcium apatites.
AB - The present study reports the variations in phase content of biphasic mixtures
and structural changes induced by different levels of strontium addition in
calcium-deficient apatite (Ca/P = 1.60) powders during heat treatment. The
synthesis was attempted by an in situ aqueous precipitation technique and X-ray
diffraction, Raman spectroscopy and Rietveld refinement of the powder X-ray
diffraction data were employed for comprehensive analysis. The results confirm
the preferential occupancy of Sr(2+) at two different Ca(2+) sites of the
hydroxyapatite [Ca10(PO4)6(OH)2, HAP] lattice, with the Ca(2+) (2) site
accommodating more Sr(2+) than the Ca(2+) (1) site. Increasing Sr(2+) addition in
calcium-deficient apatite has led to a decline in the phase content of beta
tricalcium phosphate [beta-Ca3(PO4)2, beta-TCP] in biphasic mixtures of HAP and
beta-TCP. Sr(2+) addition exceeding the critical limit of a (Ca + Sr)/P > 1.75
molar ratio has resulted in the formation of CaO as an additional phase, and this
justifies the lack of enough PO4(3-) ions to promote any kind of calcium
phosphate precipitation. Sr(2+) accommodation in the lattice sites of HAP has
induced an increase in the lattice parameters and has also led to the significant
distortion of the PO4 tetrahedron and OH groups, confirmed by Raman and FT-IR
spectroscopic techniques.
PMID- 25851343
TI - Endovascular Treatment of Middle Cerebral Artery Aneurysm with the LVIS Junior
Stent.
AB - BACKGROUND: Middle cerebral artery (MCA) aneurysms often occur in small parent
vessels and are incorporated with the orifice of acute-angled efferent branch
vessels. Endovascular treatment for these aneurysms remains technically
challenging. This study aimed to assess the clinical safety and efficacy of the
Low-profile Visualized Intraluminal Support Junior (LVIS Jr) stent for
embolization of MCA aneurysms. METHODS: Eighteen intracranial aneurysms,
including 13 unruptured and 5 ruptured aneurysms, were treated with LVIS Jr stent
assisted coil embolization. The clinical data and technical results are
presented. RESULTS: A total of 18 stents were successfully delivered to the
target aneurysms, and the technical success rate was 100%. There was complete
occlusion in 8 (44.4%) of 18 cases, neck remnants in 7 (38.9%) cases, and partial
occlusion in 3 (16.7%) cases. In-stent thrombosis occurred in 1 case, and the
symptoms disappeared after transvenous tirofiban injection. The modified Rankin
Scale score at discharge was 0 in 14 patients, 1 in 3 patients, and 2 in 1
patient. CONCLUSIONS: The LVIS Jr stent provided excellent trackability and
deliverability and is safe and effective for the treatment of wide-necked MCA
aneurysms with tortuous and smaller parent vessels.
PMID- 25851344
TI - Effects of mental practice with action observation training on occupational
performance after stroke.
AB - BACKGROUND: Studies on whether mental practice (MP) in patients with stroke using
action observation training (AOT) is effective in improving physical performance
are still insufficient. To examine the effects of MP on both occupational
performance and motor function to complement studies relevant to MP with AOT.
METHODS: Subjects of this study were 3 individuals who were diagnosed with
stroke. We used an A-B-A study design with follow-up evaluation, which is a type
of reversal single experimental research design. A total of 20 experimental
sessions were conducted. To assess the long-term effect of MP with AOT, follow-up
baseline measurements were made after 2 weeks without MP. Three-dimensional
motion analysis and electromyography were conducted during each of the 20
sessions. The Motor Activity Log and Assessment of Motor and Process Skills were
measured 3 times: in the pre-MP phase, the post-MP phase, and the 2-week follow
up phase. RESULTS: Occupational performance improved after intervention in all 3
subjects when applying an MP task using AOT. All subjects showed improvement of
motor functions, including smoothness of movement, agonistic muscle activation,
and co-ordination. The treatment effect continued after 2 weeks. CONCLUSIONS: MP
using AOT in patients with stroke is an effective treatment protocol to improve
occupational performance and motor function. Thus, MP using AOT may be applicable
for treating stroke patients with stroke not only while they are in the hospital
but also at home or in the community.
PMID- 25851345
TI - Do patients and health care professionals view the communication processes of
clinical research differently? A Rasch analysis from a survey.
AB - RATIONALE AIMS AND OBJECTIVES: The increasing amount of the clinical research
conducted in the primary health care has enabled extending research beyond
traditional settings, but this transfer has implied some trade-offs. Health care
professionals who conduct research with trusted patients require assuming the
ethical standards of research and communication skills to enable patients'
autonomy and freedom of choice. This study aims to measure the opinions of health
professionals and patients on issues of communication in clinical research.
METHOD: A cross-sectional study with health care professionals and patients from
primary health care centres in Barcelona (Spain). Each group completed a similar
self-administered questionnaire. A Rasch model was fitted to data. After
examination of goodness-of-fit, differences between groups were compared using
analysis of variance, and patients' measures were calibrated to professionals'
measures to compare overall mean measures. RESULTS: Professionals and patients
found the ethical attitudes most difficult to endorse related to trust in
clinical researchers and conflicts of interest. Patients' perceptions of
professional ethical behaviour were significantly lower than professionals'.
Different item functioning between nurses and family doctors was found in the
item on seeking ethical collaboration when collaborating in clinical research.
Effective knowledge of ethical norms was associated with greater perceived
ethical values in clinical research and confidence in health care professionals
among patients. CONCLUSIONS: Differences in the views of the communication
process between patients and professionals could alert research boards, health
care institutions and researchers to the need for greater transparency, trust and
ethical instruction when patients are involved in clinical research.
PMID- 25851346
TI - Synergistic effect between celecoxib and luteolin is dependent on estrogen
receptor in human breast cancer cells.
AB - The anti-cancer effects of celecoxib and luteolin are well known. Although our
previous study demonstrated that the combination of celecoxib and luteolin
synergistically inhibits breast tumor growth compared with each of the treatments
alone, we did not uncover the molecular mechanisms of these effects. The aims of
our present study were to compare the effects of a celecoxib and luteolin
combination treatment in four different human breast cell lines and to determine
the mechanisms of action in vitro and in vivo. The synergistic effects of a
celecoxib and luteolin combination treatment yielded significantly greater cell
growth inhibition in all four breast cancer cell lines compared with the single
agents alone. In particular, combined celecoxib and luteolin treatment
significantly decreased the growth of MDA-MB-231 cancer cells in vivo compared
with either agent alone. The celecoxib and luteolin combination treatment induced
synergistic effects via Akt inactivation and extracellular signal-regulated
kinase (ERK) signaling inhibition in MCF-7 and MCF7/HER18 cells and via Akt
inactivation and ERK signaling activation in MDA-MB-231 and SkBr3 cells. These
results demonstrate the synergistic anti-tumor effect of the celecoxib and
luteolin combination treatment in different four breast cancer cell lines, thus
introducing the possibility of this combination as a new treatment modality.
PMID- 25851347
TI - Upregulated TRIO expression correlates with a malignant phenotype in human
hepatocellular carcinoma.
AB - Triple functional domain protein (TRIO) is an evolutionarily conserved Dbl family
guanine nucleotide exchange factors (GEFs) involved in cell proliferation and
progression of some types of cancer. However, the expression and prognostic role
of TRIO in hepatocellular carcinoma (HCC) have not yet been determined.
Therefore, we attempted to determine the impact of TRIO on the clinical outcome
of HCC patients to further identify its role in HCC. TRIO expression was examined
using quantitative real-time PCR (qRT-PCR) and Western blotting in nonmalignant
liver cells, HCC cells, and 93 paired of HCC tissues and adjacent noncancerous
tissues. Statistical analyses were used to assess associations between TRIO
expression and clinicopathological and prognostic factors. Small interfering RNA
(siRNA)-mediated TRIO inhibition was performed in Hep3B and Huh7 cells to
elucidate its roles in HCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay was employed to measure cell proliferation, and apoptosis
assay was analyzed by flow cytometry, respectively. Adhesion and transwell
invasion assay were performed to determine the invasion ability of HCC cells in
vitro. TRIO was significantly upregulated in the HCC cell lines and tissues
compared with the nonmalignant liver cells and adjacent noncancerous liver
tissues. In addition, high TRIO expression level associated with lymph node
metastasis (P = 0.0183), clinical tumor node metastasis (TNM) stage (P =
0.0.0106), and decrease in overall survival (OS) (P = 0.017). Knockdown of TRIO
on Hep3B and Huh7 cell lines suppressed cell proliferation and migration and
induced apoptosis. Furthermore, silencing TRIO expression led to decrease of ras
related C3 botulinum toxin substrate 1 (Rac1), p-P38, B cell lymphoma 2 (BCL-2),
and matrix metallopeptidase 9 (MMP-9). Our results demonstrated that TRIO protein
expression is elevated and associated with a worse over survival rates in
patients with HCC. Aberrant expression of TRIO might play an important role in
HCC through promoting cell proliferation and invasion, and TRIO may be a novel
therapeutic target for the treatment of HCC.
PMID- 25851348
TI - Decreased MT1-MMP in gastric cancer suppressed cell migration and invasion via
regulating MMPs and EMT.
AB - Membrane type 1-matrix metalloproteinase (MT1-MMP) has been identified to play a
significant role in several types of cancers, but little is known about the
significance of MT1-MMP in gastric cancer patients. The purpose of this study is
to investigate the involvement of MT1-MMP in tumor progression of gastric cancer.
MT1-MMP expression levels were examined in gastric cancer tissues and cells, and
normal gastric tissues and cells. The effects and molecular mechanisms of MT1-MMP
expression on cell proliferation, migration, and invasion were also explored. In
our results, MT1-MMP messenger RNA (mRNA) and protein expression levels were
significantly increased in gastric cancer tissue. Moreover, the overexpression of
MT1-MMP was positively associated with the status of clinical stage and lymph
node metastasis through real-time PCR. Furthermore, knocking down MT1-MMP
expression significantly suppressed the cell migration and invasion in vitro and
regulated the expression of MMPs and epithelial-mesenchymal transition (EMT)
associated genes. In conclusions, our study demonstrates that MT1-MMP was
overexpressed in gastric cancer tissue, and reduced expression of MT1-MMP
suppressed cell migration, invasion, and through regulating the expression of
MMPs and the process of EMT in gastric cancer.
PMID- 25851349
TI - Mdig, a lung cancer-associated gene, regulates cell cycle progression through
p27(KIP1).
AB - Mineral dust-induced gene (mdig) can accelerate cell proliferation. The aim of
this study is to investigate the mechanism by which mdig regulates cell
proliferation. A549 cells were transfected with siRNA specifically targeting
mdig. Cell proliferation and cell cycle progression were measured using MTT assay
and cell cycle analysis, respectively. Furthermore, real-time reverse
transcription quantitative-polymerase chain reaction (RT-qPCR) was performed in
A549 cells transfected with mdig siRNA to examine the expression levels of the
cell cycle related genes such as p18(INK4c), p19(INK4d), p21(WAF/CIP1),
p27(KIP1), p57(KIP2), cyclin D1, and cyclin E. To further explore the effect of
mdig on p27(KIP1), the expression levels of total p27(KIP1) and its subtypes
pT187-p27(KIP1) and pS10-p27(KIP1) were assessed by Western blotting. In vivo,
Western blotting was performed to check the expression levels of mdig and
p27(KIP1) in human lung cancer tissues, para-cancerous normal lung tissues, and
para-bronchial stumps. Knockdown of mdig induced increases in p27(KIP1), both on
mRNA and protein levels. Furthermore, the phosphorylation of p27(KIP1) at its
Thr187 site was also inhibited. Importantly, in lung cancer tissues, upregulation
of mdig expression accompanies with the downregulation of p27(KIP1) expression
and in bronchial stump, vice versa. The data suggest that mdig-mediated
inhibition of p27(KIP1) is important for cell proliferation and tumor formation
and reveal therapeutic potential of p27(KIP1) for lung cancer.
PMID- 25851351
TI - Walking bundles of habits (and response-outcome associations) (Commentary on
Liljeholm et al.).
PMID- 25851350
TI - Influence of CCND1 G870A polymorphism on the risk of HBV-related HCC and cyclin
D1 splicing variant expression in Chinese population.
AB - The G870A polymorphism in the exon 4/intron 4 boundary of CCND1 gene is thought
to influence the generation of two mRNAs (cyclin D1a and cyclin D1b). The "A"
allele codes for a truncated variant, cyclin D1b, which may have higher
transforming activity. Herein, the tumor relevance of G870A polymorphism, the
association between cyclin D1 variant expression and G870A genotype, and the
oncogenic potential of cyclin D1 variants in HBV-related hepatocellular carcinoma
(HCC) were examined. We found that there is no significant difference of G870A
distribution among the HCC, chronic HBV (CHB) infection, cirrhotic CHB, and
healthy control groups. Stratification analysis revealed that in younger patients
(ages <= 50), cirrhotic CHB patients with AA genotype had an increased risk of
developing HCC with odds ratio of 1.943 (95 % CI 1.022-3.694, p = 0.0411) as
compared with AG/GG genotypes. The two variants were both transcripted from "A"
and "G" alleles, and neither cyclin D1a nor D1b production was influenced by
G870A genotype in HCC. The expression of both cyclins D1a and D1b decreased in
HCC tissues (p = 0.003, p = 0.005), while increased in adjacent nontumor tissues
as compared with normal liver tissues (p = 0.045, p = 0.034). Overexpression of
cyclin D1a or D1b could promote the cell proliferation and cell-cycle progression
in Huh-7 and LO2 cell lines. Collectively, our data suggest that G870A
polymorphism has only very limited predictive value for HBV-related HCC. Both
cyclins D1a and D1b could promote cell proliferation, which might contribute to
the potential oncogenic role of cyclin D1 variants during the precancerous
cirrhotic stage of hepatocarcinogenesis.
PMID- 25851352
TI - Aortic and coronary aneurysms: are they really distinct entities?
PMID- 25851353
TI - Clinical Utility of CAPE-V Sentences for Determination of Speaking Fundamental
Frequency.
AB - OBJECTIVES/HYPOTHESIS: Sentence stimuli from the Consensus Auditory-Perceptual
Evaluation of Voice (CAPE-V) were compared with standard speaking fundamental
frequency (SF0) tasks to establish clinical utility of the sentence stimuli for
standardized assessment of SF0. STUDY DESIGN: Using a within-participant repeated
measures design, 60 consented participants (30 males and 30 females) completed
the study. METHODS: Participants provided 10 acoustic samples (six CAPE-V
sentences and four additional standard tasks), counterbalanced for order effect,
for determining SF0. A within-participant repeated measures analysis of variance
was used in a 2 (males vs females) by 11 (10 tasks and CAPE-V sentence average)
design to determine significant differences in SF0 with significance set at alpha
< .05. RESULTS: Significant differences were found for the CAPE-V sentences
"Peter will keep at the peak" and "How hard did he hit him" with seven of the
remaining tasks and the CAPE-V average determined to be statistically similar in
female participants. No significant differences were found for male participants.
CONCLUSIONS: Findings from this study indicate that taken individually, four of
the CAPE-V sentences and the average of the six CAPE-V sentences may be used
instead of longer tasks to determine SF0 in nonvoice-disordered individuals. This
may streamline clinical service by using the CAPE-V sentences for both
standardized acoustic and perceptual voice assessments.
PMID- 25851354
TI - Collagen content and distribution in the normal and transplanted human heart: A
postmortem quantitative light microscopic analysis.
AB - Endomyocardial biopsies in heart transplant patients offer the opportunity to
study the myocardial interstitium in the context of myocardial function. For that
purpose endomyocardial biopsies should reliably reflect the composition of the
entire myocardium. We determined whether the collagen content in the
subendocardial region of the right side of the interventricular septum (site of
right ventricular endomyocardial biopsy), in 16 normal and 30 transplanted human
hearts, is representative for the entire myocardium. Moreover we determined
whether or not the mean collagen content of the myocardium is altered along with
the posttransplantation survival time and which factors might contribute to the
development of interstitial myocardial fibrosis. Transmural sections of the right
and left ventricular free wall and interventricular septum were stained with
Sirius red, which specifically stains collagen fibers. Collagen in the
subendocardial region and central parts of the myocardium was quantified using a
digital image analyzer. In normal hearts the mean collagen content of the
subendocardial region of the right side of the interventricular septum (site of
right ventricular endomyocardial biopsy) correlates well with the mean collagen
content of the right ventricular wall and the center of the interventricular
septum, but it does not reliably reflect the mean collagen content of the left
ventricular free wall. In transplanted hearts the collagen content at the site of
right ventricular endomyocardial biopsy correlates highly with the mean collagen
content of the entire myocardium. In transplanted hearts the increase in collagen
content is a result mainly of an increase in collagen of the left ventricular
free wall. We conclude that in heart transplant patients, right ventricular
endomyocardial biopsies have potential value in the analysis of the causes of
left ventricular dysfunction. In transplanted human hearts, the
posttransplantation survival time correlates positively with the collagen
content, and this is attributable mainly to an increase in the collagen of the
left ventricular free wall.
PMID- 25851355
TI - A practical and rapid method of histological processing for examination of
coronary arteries containing metallic stents.
AB - A practical and rapid method was developed to study vascular pathology after
implantation of metal endoprostheses (stents) that are used as internal splinting
devices of tube-like structures. This method obviates the need for time-consuming
grinding of thick sawing sections or removal of the prosthesis prior to
histological processing, allowing for detailed analysis of the tissue in general,
but especially of the stent-tissue interface. The vessels, with the metal stents
still in place, were dehydrated in graded series of ethanol and embedded in
methyl methacrylate. Using a motor-driven rotary microtome, 3- to 5-MUm sections
were easily cut. After deplastination, routine and special histological stainings
were performed according to standard protocols for paraffin sections. This method
proved to save time, compared with sawing sections, while allowing for a more
complete examination of the stenttissue interface than is possible with routine
paraffin techniques.
PMID- 25851356
TI - Congenital stenotic arteriopathy with medial dysplasia of aorta, pulmonary
artery, and their major branches.
AB - This report describes the morphological findings in a young child with congenital
stenotic arteriopathy who died suddenly following arteriography. Hyperplasia of
all of the medial components had produced severe thickening of the wall of the
aorta (mean number of lamellar units = 133 in the thoracic aorta and 125 in the
abdominal aorta), the pulmonary artery, and their major proximal branches,
resulting in significant luminal narrowing. Bilateral renal artery stenosis,
attributable mainly to intimal longitudinal smooth muscle hyperplasia associated
with fibroelastosis, was the cause of her systemic hypertension. The left
ventricle showed healed subendocardial infarction.
PMID- 25851357
TI - A fenestrated aortic valve contributing to iatrogenic aortic insufficiency post
mitral valve replacement.
AB - A case of an unusual local complication of cardiac valvular surgery is presented.
Distortion of the geometry of the aortic valve base by a prosthetic mitral valve
sewing ring allowed aortic insufficiency through the aortic valve's central
orifice, as well as through an aortic valve cusp fenestration. During the 6 years
after valve surgery, this patient developed chronic left heart failure
contributed to by the aortic insufficiency and eventually, at age 65, required
cardiac transplantation. Surgeons and pathologists should be aware of this
unusual local complication of cardiac valve surgery, as it may have serious
consequences.
PMID- 25851358
TI - Left ventricular rupture through an area of fatty infiltration: Case report and
review of the literature.
AB - An exceptionally rare case of left ventricular rupture through an area of fatty
infiltration of the myocardium (lipomatosis cordis) is presented. The rupture
occurred in a 62-year-old white woman during a dobutamine stress echo procedure.
The autopsy revealed biventricular lipomatous infiltration with marked atrophy of
myocardial fibers. There was no evidence of acute or old myocardial infarction.
The literature is reviewed and pathology and clinical consequences of this
condition are discussed.
PMID- 25851359
TI - Sudden death from coronary artery disease in a 28-year-old munitions worker: An
example of stenosing intimal proliferation as an exaggerated response to injury.
AB - A 28-year-old munitions worker died suddenly and unexpectedly early on a Monday
morning. At autopsy, the major epicardial coronary arteries were diffusely and
concentrically thickened, and the luminal cross-sectional area was reduced by at
least 90%. Examination by light microscopy showed extensive intimal smooth muscle
hyperplasia without atheroma formation. The intimal proliferation was similar to
that reported in response to various forms of coronary artery injury, including
balloon angioplasty, surgical endarterectomy, and chronic cardiac allograft
vasculopathy. In addition, there was evidence of acute and chronic myocardial
ischemia. The patient's only known risk factor for ischemic heart disease was
occupational exposure to nitrates, in conjunction with lack of exposure on
weekends. Although symptoms of myocardial ischemia in munitions employees are
generally considered functional in origin (attributable to vasospasm), the
findings in this case suggest that nitrates or, more accurately, repetitive
nitrate withdrawal for several days at a time may also induce structural changes
within coronary arteries.
PMID- 25851360
TI - External cardioversion-related cardiac damage.
AB - Significant iatrogenic injury of the heart is an uncommon occurrence. Described
is a unique case of electrical cardioversion injury of the heart. A 58-year-old
man underwent orthotopic cardiac transplant for end-stage ischemic heart disease.
Five months posttransplantation, he experienced severe acute rejection and
developed progressive heart failure and atrial flutter, which were not responsive
to medical treatment. The patient required external electrocardioversions, which
were unsuccessful despite progressively increased voltage. He died of heart
failure approximately two weeks after admission. Postmortem examination revealed
the sequelae of acute and chronic heart failure, patchy myocardial fibrosis
(healing rejection), ongoing mild to moderate acute rejection, and marked
subepicardial wedge-shaped necrosis in the left ventricular free wall. The
microscopic age of these areas was consistent with their occurrence at the time
of attempted cardioversions, approximately seven days before death. Pathologists
should be aware of this iatrogenic injury (and its morphologic pattern), so that
it is not confused with ischemic or other forms of myocardial damage.
PMID- 25851361
TI - Myocardial toxoplasmosis complicating cardiac transplant.
AB - The increase in numbers of immunocompromised patients has been reflected by an
increasing frequency of opportunistic infections. Of these, Toxoplasma gondii has
been reported as a significant human pathogen following cardiac transplantation.
In this setting, quiescent toxoplasma myocardial cysts may become active after
implantation into a therapeutically immunosuppressed host. The consequences of
infection are significant and carry a high morbidity and mortality. We present
the clinical and pathologic characteristics of a patient with toxoplasma
infection complicating cardiac transplant and review previously reported cases of
this entity.
PMID- 25851362
TI - Ultrastructural and immunohistochemical studies on myocardial biopsies from a
patient with eosinophilic endomyocarditis.
AB - Right ventricular endomyocardial biopsy specimens from a 13-year-old boy with
hypereosinophilia were studied by light and electron microscopy using the EG2
monoclonal antibody, which recognizes a common epitope of eosinophil cationic
protein and eosinophil protein-X. Although the endocardial layer was of normal
thickness, many eosinophils, mononuclear cells, and free eosinophil granules were
observed in the endocardium and in the vicinity of degenerated myocardial cells.
Under electron microscopy, many of the specific granules in and out of
eosinophils had lost their crystalloid internae and displayed reversed density,
and there were many degranulated eosinophils with reduced number of granules.
Immunohistochemically, large amounts of eosinophil cationic protein and protein-X
were observed within cardiocytes when many of them were degenerated. Deposits of
the proteins were also found in some small vessels. On electron microscopy,
accumulations of gold particles, which bind to eosinophil cationic protein and
protein-X, were seen in association with specific granules and on the
myofilaments in both degenerated and normal-appearing cardiocytes. The presence
of eosinophil cationic proteins within cardiocytes may play an important role in
the pathogenesis of eosinophilic endomyocardial disease.
PMID- 25851363
TI - Diagnosis of primary cardiac leiomyosarcoma by endomyocardial biopsy.
AB - We report a case of a primary right ventricular leiomyosarcoma in a 58-year-old
woman diagnosed by endomyocardial biopsy. Clinical findings included a 5-year
history of atypical chest pain and atrial fibrillation as well as a 30-lb weight
loss. A ventricular mass was identified by echocardiography and magnetic
resonance imaging, and an endomyocardial biopsy was performed. Biopsy was guided
by right ventriculography, which revealed a mobile mass in the cavity of the
right ventricle. Light microscopy revealed a fasciculated, spindle cell sarcoma,
most consistent with leiomyosarcoma, and immunohistochemical staining for muscle
specific actin was strongly positive in nearly all tumor cells, confirming its
myogenous differentiation. Endomyocardial biopsy provided a definitive tissue
diagnosis of this rare primary malignant cardiac neoplasm without the need for a
surgical procedure.
PMID- 25851364
TI - Emergent long-range synchronization of oscillating ecological populations without
external forcing described by Ising universality.
AB - Understanding the synchronization of oscillations across space is fundamentally
important to many scientific disciplines. In ecology, long-range synchronization
of oscillations in spatial populations may elevate extinction risk and signal an
impending catastrophe. The prevailing assumption is that synchronization on
distances longer than the dispersal scale can only be due to environmental
correlation (the Moran effect). In contrast, we show how long-range
synchronization can emerge over distances much longer than the length scales of
either dispersal or environmental correlation. In particular, we demonstrate that
the transition from incoherence to long-range synchronization of two-cycle
oscillations in noisy spatial population models is described by the Ising
universality class of statistical physics. This result shows, in contrast to all
previous work, how the Ising critical transition can emerge directly from the
dynamics of ecological populations.
PMID- 25851365
TI - [Every hour causes damage, the last one kills....].
PMID- 25851366
TI - [Schistosomiasis].
PMID- 25851368
TI - Age and gender as independent predictors of violence under the influence of
alcohol in Zurich, Switzerland.
AB - Violent behaviour associated with alcohol consumption is frequently reported by
different media. Clinical data analysing the correlation between alcohol
intoxication, age, gender and violence are scarce. The aim of this study was to
evaluate the influence of age, gender and blood alcohol content on violent
behaviour under the influence of alcohol under central European conditions. Three
hundred patients admitted to the emergency department were included into this
study in the time period from January 01. to December 31. 2009. The inclusion
criteria were a blood alcohol content (BAC) of >=10 mmol/l, any traumatic injury
and an age >=16 years. Violence was defined as an evitable act committed by
others leading to patient's hospitalisation. The data were compared with Wilcoxon
and chi2-test for proportions. The data were considered as significant if p<0,05.
Predictive quality was evaluated by using receiver operating characteristic (ROC)
curve. Independent predictors were analyzed by logistic regression analysis. The
average age was 36,9+/-16,9 years (range: 16-84 years), 259 (86%) males and 41
(24%) females. There was a significant difference in gender (odds ratio for
gender male 2,88; CI 95%: 1,24-6,67; p<0,001) and age dependent (odds ratio for
each year of age 0,94; CI 95%: 0,93-0,96; p<0,0001) violence with no correlation
to blood alcohol content found. Logistic regression analysis revealed male gender
and young age as an independent predictor for violence. These results clarify the
relationship between alcohol, age, gender and violence and have important
implications for municipal-level alcohol policies.
PMID- 25851369
TI - [Sport, is it really so good for health?].
AB - Physical activity is necessary for life and is one of the greatest opportunities
to improve the health of populations, although it is sometimes mixed up with
sports which can cause injuries or acute cardiac events. Nevertheless, some
sedentaries can present with metabolic adverse responses after initiation of a
well-planned, health-enhancing physical activity program. This sort of exercise
intolerance has some genetic roots and does not necessarily imply that all
physical activity should be stopped, but rather must be considered as a side
effect of therapy that needs optimizing. Individualization of exercise
prescription will always consider follow-up and has to be dynamic according to
observations made with the patient.
PMID- 25851370
TI - [When the tissue tolerance fiber tears].
AB - We report a 65 year old patient who presented with both an aneurysm of the
axillary artery and, some years later, with an acute aortic dissection type
Stanford A. After surgical intervention of the dissection in the further workup,
no specific etiology could be found. The most likely reason for the two aneurysms
was the inadequately treated hypertension. Therefore, follow-up strategies aim to
treat the risk factors which are known to promote aneurysm growth.
PMID- 25851372
TI - [Diagnosis of Lyme borreliosis].
PMID- 25851373
TI - [Not Available].
PMID- 25851374
TI - [In Process Citation].
PMID- 25851376
TI - [Ultrasound diagnosis 63. Tumor of the bladder wall, partially necrotic
(calcified)].
PMID- 25851378
TI - [Personalities in the history of medicine. Sergej Sergejewitsch Korsakow. Nikolaj
Sergejitsch Korotkow].
PMID- 25851379
TI - Erratum to: Saliva Versus Plasma Bioequivalence of Rusovastatin in Humans:
Validation of Class III Drugs of the Salivary Excretion Classification System.
PMID- 25851380
TI - Response to Commentary by W. Jost on: Pharmaceutical, Biological, and Clinical
Properties of Botulinum Neurotoxin Type A Products.
PMID- 25851381
TI - Comment on Hamada et al.: Ultrasound assessment of gastric volume in critically
ill patients.
PMID- 25851382
TI - Acute ruptured mycotic aneurysm mimicking myocardial tumor with ST elevation
myocardial infarction.
PMID- 25851383
TI - Early physical rehabilitation in intensive care patients with sepsis syndromes: a
pilot randomised controlled trial.
AB - RATIONALE: Survivors of sepsis syndromes have poor outcomes for physical and
cognitive function. No investigations of early physical rehabilitation in the
intensive care unit have specifically targeted patients with sepsis syndromes.
OBJECTIVE: To determine whether early physical rehabilitation improves physical
function and associated outcomes in patients with sepsis syndromes. METHODS:
Fifty critically ill adults admitted to a general intensive care unit with sepsis
syndromes were recruited into a prospective double-blinded randomised controlled
trial investigating early physical rehabilitation. MEASUREMENTS: Primary outcomes
of physical function (acute care index of function) and self-reported health
related quality of life were recorded at ICU discharge and 6 months post-hospital
discharge, respectively. Secondary measures included inflammatory biomarkers;
Interleukin-6, Interleukin-10 and tumour necrosis factor-alpha, blood lactate,
fat-free muscle mass, exercise capacity, muscle strength and anxiety. MAIN
RESULTS: A significant increase in patient self-reported physical function (81.8
+/- 22.2 vs. 60.0 +/- 29.4), p = 0.04) and physical role (61.4 +/- 43.8 vs. 17.1
+/- 34.4, p = 0.005) for the SF-36 at 6 months was found in the exercise group.
Physical function scores were not significantly different between groups. Muscle
strength scores were (51.9 +/- 10.5 vs. 47.3 +/- 13.6, p = 0.24) with the
standard care mean Medical Research Council Muscle Score (MRC) <48/60. The mean
change of Interleukin-10 increased and was significantly higher in the exercise
group (1.8 pg/ml, 180 % vs. 0.9 pg/ml, 90 %, p = 0.04). There was no significant
difference between groups for lactate, Interleukin-6, tumour necrosis factor
alpha, muscle strength, exercise capacity, fat-free mass or hospital anxiety.
CONCLUSION: Implementation of early physical rehabilitation can improve self
reported physical function and induce systemic anti-inflammatory effects.
PMID- 25851384
TI - Phenotypic clusters within sepsis-associated multiple organ dysfunction syndrome.
AB - INTRODUCTION: Sepsis is a devastating condition that is generally treated as a
single disease. Identification of meaningfully distinct clusters may improve
research, treatment and prognostication among septic patients. We therefore
sought to identify clusters among patients with severe sepsis or septic shock.
METHODS: We retrospectively studied all patients with severe sepsis or septic
shock admitted directly from the emergency department to the intensive care units
(ICUs) of three hospitals, 2006-2013. Using age and Sequential Organ Failure
Assessment (SOFA) subscores, we defined clusters utilizing self-organizing maps,
a method for representing multidimensional data in intuitive two-dimensional
grids to facilitate cluster identification. RESULTS: We identified 2533 patients
with severe sepsis or septic shock. Overall mortality was 17 %, with a mean
APACHE II score of 24, mean SOFA score of 8 and a mean ICU stay of 5.4 days. Four
distinct clusters were identified; (1) shock with elevated creatinine, (2)
minimal multi-organ dysfunction syndrome (MODS), (3) shock with hypoxemia and
altered mental status, and (4) hepatic disease. Mortality (95 % confidence
intervals) for these clusters was 11 (8-14), 12 (11-14), 28 (25-32), and 21 (16
26) %, respectively (p < 0.0001). Regression modeling demonstrated that the
clusters differed in the association between clinical outcomes and predictors,
including APACHE II score. CONCLUSIONS: We identified four distinct clusters of
MODS among patients with severe sepsis or septic shock. These clusters may
reflect underlying pathophysiological differences and could potentially
facilitate tailored treatments or directed research.
PMID- 25851385
TI - Direct extubation onto high-flow nasal cannulae post-cardiac surgery versus
standard treatment in patients with a BMI >=30: a randomised controlled trial.
AB - PURPOSE: Patients with a body mass index (BMI) >=30 kg/m(2) experience more
severe atelectasis following cardiac surgery than those with normal BMI and its
resolution is slower. This study aimed to compare extubation of patients post
cardiac surgery with a BMI >=30 kg/m(2) onto high-flow nasal cannulae (HFNC) with
standard care to determine whether HFNC could assist in minimising post-operative
atelectasis and improve respiratory function. METHODS: In this randomised
controlled trial, patients received HFNC or standard oxygen therapy post
extubation. The primary outcome was atelectasis on chest X-ray. Secondary
outcomes included oxygenation, respiratory rate (RR), subjective dyspnoea, and
failure of allocated treatment. RESULTS: One hundred and fifty-five patients were
randomised, 74 to control, 81 to HFNC. No difference was seen between groups in
atelectasis scores on Days 1 or 5 (median scores = 2, p = 0.70 and p = 0.15,
respectively). In the 24-h post-extubation, there was no difference in mean
PaO2/FiO2 ratio (HFNC 227.9, control 253.3, p = 0.08), or RR (HFNC 17.2, control
16.7, p = 0.17). However, low dyspnoea levels were observed in each group at 8 h
post-extubation, median (IQR) scores were 0 (0-1) for control and 1 (0-3) for
HFNC (p = 0.008). Five patients failed allocated treatment in the control group
compared with three in the treatment group [Odds ratio 0.53, (95 % CI 0.11,
2.24), p = 0.40]. CONCLUSIONS: In this study, prophylactic extubation onto HFNC
post-cardiac surgery in patients with a BMI >=30 kg/m(2) did not lead to
improvements in respiratory function. Larger studies assessing the role of HFNC
in preventing worsening of respiratory function and intubation are required.
PMID- 25851386
TI - What's new on the HPA axis?
PMID- 25851387
TI - Testing current practice is no mistake.
PMID- 25851388
TI - Response to Perner et al.: testing current practice is no mistake.
PMID- 25851389
TI - Venous-arterial CO2 to arterial-venous O2 difference ratio as a resuscitation
target in shock states?
PMID- 25851390
TI - Molding thrombus of an ECMO cannula floating in the right atrium.
PMID- 25851392
TI - Can inferior vena cava saturations be used instead of ScvO2 in children with
septic shock?
PMID- 25851391
TI - Health-related quality of life following pediatric critical illness.
AB - PURPOSE: The aims of this focused review of the literature on children surviving
critical illness were to (1) determine whether health-related quality of life
(HRQL) represents a clinically meaningful outcome measure for children surviving
critical illness and (2) evaluate the HRQL measures implemented in pediatric
critical care studies to date. METHODS: This was a focused review of the
literature from 1980 to 2015 based on a search of EMBASE/PubMed, MEDLINE and
PsycInfo assessing trends and determinants of HRQL outcomes in children surviving
critical illness. We also evaluated the psychometric properties of the HRQL
instruments used in the studies identified by examining each measure's reported
reliability, validity and sensitivity to clinical change. RESULTS: The literature
search identified 253 pediatric articles for potential inclusion in the review,
among which data from 78 studies were ultimately selected for inclusion. Of the
22 measures utilized in the studies reviewed, only four demonstrated excellent
psychometric properties for use in pediatric critical care trials. Trends in HRQL
identified in the studies reviewed suggest significant ongoing morbidity for
children surviving critical illness. Key determinants of poor HRQL outcomes
include reason for PICU admission (sepsis, meningoencephalitis, trauma),
antecedents (chronic comorbid conditions), treatments received (prolonged
cardiopulmonary resuscitation, long-stay patients, invasive technology),
psychological outcomes (post-traumatic stress disorder, parent
anxiety/depression) and social and environmental characteristics (low
socioeconomic status, parental education and functioning). CONCLUSIONS: Validated
pediatric HRQL instruments are now available. Significant impact on HRQL has been
demonstrated in acute and acute on chronic critical illness. Future pediatric
critical care interventional trials should include both mortality as well as long
term HRQL measurements to truly ascertain the full impact of critical illness in
children.
PMID- 25851393
TI - Checklist use in ICUs: a French national survey.
PMID- 25851394
TI - Erratum to: Diastolic dysfunction and mortality in septic patients: a systematic
review and meta-analysis.
PMID- 25851395
TI - Vasculitis unlimited in rheumatoid arthritis an illustrated review.
AB - Rheumatoid arthritis has a multitude of extra-articular manifestations, of which
systemic vasculitis is a clinically significant co-morbidity and co-mortality
determinant in the prognosis of the disease. Rheumatoid vasculitis may occur in
the early stage of the disease but, more commonly, in patients who have had
seropositive rheumatoid arthritis for 10 years or longer. Rheumatoid vasculitis
has a wide variety of histopathologic expressions and it may affect blood vessels
of all sizes (from vasa nervorum or vasa vasorum to the aorta; and occasionally
veins and venules). The diagnosis ideally requires biopsy or autopsy tissue
confirmation, which is discussed and illustrated in this review.
PMID- 25851396
TI - Mitochondrial DNA defects in cardiomyopathy.
AB - Abnormalities in mitochondrial DNA (mtDNA) including specific deletions and point
mutations have been found in an increasing number of cases of both dilated and
hypertrophic cardiomyopathy. The role that these mutations may play in
contributing to the cardiomyopathic phenotype is discussed in this survey of the
recent literature.
PMID- 25851397
TI - Pathogenesis of cardiomyopathy caused by anthracycline antibiotics effect of
pulmonary stenosis on the development of cardiomyopathy.
AB - This study was undertaken to elucidate the effect of pressure load on the
development of cardiomyopathy induced by daunorubicin in the right ventricle of
rabbits on which pulmonary stenosis had been performed. The right ventricular
pressure after occlusion of the pulmonary artery was approximately twice that
prior to occlusion. Pulmonary stenosis apparently produced hypertrophy of the
right ventricular myocardium within approximately 2 weeks of occlusion. In
rabbits with pulmonary stenosis, the characteristic myocardial degenerative
changes induced by daunorubicin were found on the right ventricular wall.
However, in rabbits without pulmonary stenosis, myocardial lesions were observed
only on the left ventricular wall. The pressure load acting as a mechanical
stress increases myocardial damage induced by daunorubicin. It is well known that
anthracyclines take effect on cells in which nucleic acid synthesis is augmented
and the pressure load results in the enhancement of protooncogene expression in
myocytes and a subsequent increase in protein synthesis. These results suggest
that the pressure load may play a significant role in anthracycline
cardiomyopathy by increasing protein synthesis in the myocardium.
PMID- 25851398
TI - Co-localization of fibrinolytic activators and inhibitors with macrophages in
atherosclerotic vessels.
AB - The plasmin system is involved in hemostasis and tissue remodelling. The
accumulation of plasminogen activators and their inhibitors in atherosclerotic
lesions may be due to invasion of inflammatory cells in the vessel wall. High
concentrations of macrophages are associated with increased risk of
atherosclerotic plaque rupture. By immunohistochemistry on circumferential serial
sections of atherosclerotic and healthy vessels the morphological association of
plasminogen activators and inhibitors with macrophages was studied. Urokinase
plasminogen activator (u-PA), plasminogen activator inhibitor type 2 (PAI-2), and
macrophages were mainly expressed within plaques while tissue plasminogen
activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also
expressed outside plaque lesions. Computer assisted image analysis on diseased
vessels showed that regulatory proteins of the fibrinolytic system were found
more often in areas positive for macrophages than in other parts of the sections
(p < 0.001). u-PA was significantly more defined to areas positive for
macrophages than tissue plasminogen activator (t-PA) and plasminogen activator
inhibitor type 1 (PAI-1) (p < 0.05). Similarly, PAI-2 expression was more
associated with macrophage distribution than PAI-1 (p < 0.05). Tumor necrosis
factor alpha (TNFalpha), an inflammatoric mediator of macrophages, had the same
levels of co-localization with macrophages as u-PA and PAI-2. These results
suggest that u-PA and PAI-2 might be key factors for inflammatory regulation of
plasmin mediated proteolysis in the vessel walls.
PMID- 25851399
TI - Acid hydrolyzable aldehydes in long-term stored commercial bioprosthetic heart
valves implications for calcification.
AB - There is evidence that glutaraldehyde used routinely in the fixation process of
bioprosthetic heart valves may be a major factor in their subsequent
calcification. A further complication is introduced by the use of a formaldehyde
treatment step, whether for sterilization or storage. The effects of this second
aldehyde on calcification is also unknown. The aim of the present work is to
determine the degree of glutaraldehyde and formaldehyde incorporation into
commercial valve leaflets and to establish whether there is a relationship
between the aldehyde treatment and tissue calcification. Both pre- and post
implantation concentrations of aldehydes were estimated by high performance
liquid chromatography of acid hydrolyzates of commercial valve tissue. Control
samples were taken from freshly prepared porcine aortic valves and bovine
pericardium fixed in glutaraldehyde. The degree of calcification was investigated
using the rat subcutaneous implant model. Samples were retrieved after 56 days
and calcium estimated by atomic absorption spectroscopy. The results indicated
that storage of both porcine and pericardial valves for periods of 5 years or
longer reduced calcification. A greater reduction in calcification was noted when
tissue was treated sequentially with glutaraldehyde and formaldehyde rather than
glutaraldehyde alone. From this work it can be concluded that bioprosthetic
valves calcify less in the rat model when they are stored for extended periods of
time in glutaraldehyde solution. This effect is enhanced when formaldehyde
storage is employed.
PMID- 25851400
TI - Conditions associated with extreme hyperferritinaemia (>3000 MUg/L) in adults.
AB - BACKGROUND: The clinical significance of extreme hyperferritinaemia has come
under scrutiny with the increasing recognition of haemophagocytic
lymphohistiocytosis (HLH) in adults. Most studies of hyperferritinaemia have
focused on serum ferritin greater than 1000 MUg/L, often in ambulatory patients.
The conditions associated with more extreme hyperferritinaemia are poorly
understood. AIMS: To examine conditions associated with extreme
hyperferritinaemia greater than 3000 MUg/L in acutely ill adults at a quaternary
care hospital. METHODS: Patients with serum ferritin greater than 3000 MUg/L at
Vancouver General Hospital between 1 August 2011 and 1 August 2012 were
identified. Those over 18 years of age and with clinical data available were
included in the study. RESULTS: Eighty-three subjects were identified. Twenty-one
cases (25%) were due to transfusional iron overload, 16 (19%) due to liver
disease and 15 (18%) due to mixed factors. Haemophagocytic lymphohistiocytosis
(HLH) was diagnosed in six of 83 patients (7%) with ferritin greater than 3000
MUg/L, but six of eight patients (75%) with ferritin greater than 20 000 MUg/L.
CONCLUSIONS: Extreme hyperferritinaemia greater than 3000 MUg/L is uncommon in
adult patients. The highest serum ferritin values are seen in HLH, but the
differential diagnosis for serum ferritin greater than 3000 MUg/L remains broad
with iron overload and liver disease being the most common causes.
PMID- 25851401
TI - Approaching the alloy limit of thermal conductivity in single-crystalline Si
based thermoelectric nanocomposites: A molecular dynamics investigation.
AB - Single-crystalline Si-based nanocomposites have become promising candidates for
thermoelectric applications due to their prominent merits. Reducing the thermal
conductivity kappa without deteriorating the electrical properties is the key to
improve their performance. Through non-equilibrium molecular dynamics
simulations, we show that kappa of single-crystalline Si-based nanocomposites can
be reduced to the alloy limit by embedding various nanoinclusions of similar
lattice constants but different lattice orientations or space symmetries with
respect to the matrix. The surprisingly low kappa is mainly due to the large
acoustic phonon density of states mismatch caused by the destruction of lattice
periodicity at the interfaces between the nanoinclusions and matrix, which leads
to the substantial reduction of phonon group velocity and relaxation time, as
well as the enhancement of phonon localization. The resulting kappa is also
temperature-insensitive due to the dominance of boundary scattering. The increase
in thermal resistance induced by lattice structure mismatch mainly comes from the
nanoinclusions and the channels between them and is caused by the enhanced
boundary scattering at the interfaces parallel to the heat flux. Approaching the
alloy limit of kappa with potentially improved electrical properties by fillers
will remarkably improve ZT of single-crystalline Si-based nanocomposites and
extend their application.
PMID- 25851402
TI - Magnetic resonance imaging has no role in diagnosing the origin of pain in
patients with overwhelmingly painful inguinal hernia.
AB - PURPOSE: Clinical tools for predicting postoperative pain should be developed to
provide better care for patients. The aims of this study were to evaluate
preoperative magnetic resonance imaging (MRI) findings to reveal reasons for
overwhelming pain in patients with inguinal hernia and to detect changes in
quality-of-life (QoL) and pain scores preoperatively and following laparoscopic
totally extraperitoneal (TEP) repair of inguinal hernia. METHODS: Twenty-two
patients aged 18-50 years presenting with extremely painful inguinal hernias
(highest pain scores >50, scale 0-100) were examined with MRI prior to operative
treatment with TEP repair. Postoperative follow-up lasted 6 months and consisted
of questionnaires regarding functional status, pain, QoL and possible
complications. Postoperative MRI scans were performed only in cases of
preoperative findings on the MRI or prolonged inguinal pain persisting over 6
months. RESULTS: Prolonged postoperative pain could not be predicted from
preoperative MRI scans, because no signs of the pain's origin such as pubic
periostal irritation, bone marrow edema, pelvic bone or hip joint abnormalities,
or lower abdominal muscle hemorrhage were detected in MRI. TEP repair of inguinal
hernia significantly improved the patients' quality of life and relieved pain
symptoms. High preoperative pain scores were major predictors of prolonged
postoperative pain. CONCLUSIONS: Carefully evaluated preoperative pelvic MRI was
usually normal in patients with high pain scores prior to operation. Preoperative
pain scores may serve as indicators of development of prolonged inguinal pain.
PMID- 25851403
TI - Anti-diabetic therapies and the risk of acute pancreatitis: a nationwide
retrospective cohort study from Taiwan.
AB - AIMS: To examine the relationship between different anti-diabetic therapies
(dipeptidyl peptidase-4 (DPP-4), metformin and sulfonylureas) and risk of acute
pancreatitis among type 2 diabetic patients in Taiwan, and explore each drug's
dose-response relationship. MATERIALS AND METHODS: We derived a nationwide
retrospective cohort of patients with type 2 diabetes in Taiwan. The inclusion
criteria are adult diabetic patients with continuous baseline enrollment, new
users of the studied drugs, and without missing demographics. There were 4113/101
498/44 772 DPP-4/Metformin/Sulfonylurea users. Adjusted hazards ratios for
pancreatitis associated with DPP-4, derived from Cox proportional hazard models
with propensity score weighting, were estimated; dose-response analyses were also
conducted. RESULTS: Dipeptidyl peptidase-4 was statistically significantly
associated with a decreased risk of acute pancreatitis compared with
sulfonylureas (adjusted HR: 0.36, 95%CI [0.17, 0.75]) but not metformin (adjusted
HR: 0.67, 95%CI [0.32, 1.41]); metformin was statistically significantly
associated with a lower risk of pancreatitis than sulfonylurea (adjusted HR: 0.
53; 95%CI [0.37, 0.76]). In addition, low-dose metformin was statistically
significantly associated with a lower risk of pancreatitis compared with high
dose metformin (HR: 0.65; 95%CI [0.44, 0.97]). CONCLUSIONS: Our findings suggest
that sulfonylureas may potentially be associated with an increased risk of
pancreatitis compared with DPP-4 or metformin. Studies with longer follow up,
larger sample sizes, and more precise capture of confounders may be needed to
determine the risk of pancreatitis associated with incretin based therapies.
PMID- 25851404
TI - [Fine-needle aspiration in an extremely late post-traumatic iris cyst].
AB - CLINICAL CASE: A 45 year-old woman with unknown ophthalmology history complained
of pain, redness and visual acuity (VA) loss in her left eye for the last three
weeks. A serous iris cyst with an overlying peripheral corneal leukoma was
located in the iris stroma using ultrasonic biomicroscopy. It was assumed that it
was secondary to a penetrating trauma from her childhood. The cyst healed and VA
improved after fine-needle aspiration and partial posterior synechiolysis.
DISCUSSION: Iris inclusion cysts may appear many years after penetrating trauma
or surgery. Fine-needle aspiration is a good choice for its diagnosis and
treatment.
PMID- 25851405
TI - Zero-profile integrated plate and spacer device reduces rate of adjacent-level
ossification development and dysphagia compared to ACDF with plating and cage
system.
AB - STUDY DESIGN: Retrospective case-control study. PURPOSE: To compare the safety
and efficacy of the Zero-profile (Zero-p) integrated plate and spacer device to
that of an anterior cervical plate and cage in patients undergoing anterior
cervical discectomy and fusion (ACDF). Anterior cervical plating system has
provided good results, including higher fusion rate and improved alignment since
its use. However, adjacent-level ossification development (ALOD) and dysphagia
have been usually reported associating with plates. METHODS: This was a
retrospective control study. Sixty-two patients with cervical radiculopathy or
myelopathy were treated with an anterior plate and cage or Zero-p implant between
January 2011 and December 2011. The mean follow-up was 33.1 months in the plate
and cage group and 30.6 months in Zero-p group. Patient demographics, operative
details and complications were reviewed. The clinical outcomes were evaluated
using the Japanese Orthopaedic Association (JOA) scores and JOA recovery rate
before and after operations. Incidence of cephalad and caudal ALOD on the lateral
radiographs was studied at preoperation, immediate postoperation and last follow
up. Incidence of dysphagia was also recorded after operation according to Bazaz
Yoo dysphagia index. RESULTS: Thirty-two patients received an anterior plate and
cage and 30 received the Zero-p implant. There were no statistical differences in
patient demographics, operative details between the two groups. The JOA scores
significantly increased compared with preoperational measurements in both groups
(p < 0.05), but the JOA recovery rate was similar (72.2 % for plate and cage
group and 77.0 % for Zero-p group, p > 0.05). ALOD occurred in 12 (18.8 %) of the
64 cephalad and caudal adjacent segments in plate with cage group, and only 1
(1.6 %) of 63 adjacent levels (including three noncontiguous cases) presented
with ALOD in Zero-p group. The difference was significant (p < 0.01). The
incidence of dysphagia in the Zero-p group was lower compared with that in the
plate with cage group, and the symptom duration was much shorter (p < 0.01). Both
groups had no adverse events associated with the implant or implant surgery.
CONCLUSIONS: The Zero-profile implant is safe and efficacious after ACDF. It can
reduce the rate of adjacent-level ossification development and dysphagia compared
to anterior plate and cage.
PMID- 25851406
TI - How salinity and temperature combine to affect physiological state and
performance in red knots with contrasting non-breeding environments.
AB - Migratory shorebirds inhabit environments that may yield contrasting salinity
temperature regimes-with widely varying osmoregulatory demands, even within a
given species-and the question is: by which physiological means and at which
organisational level do they show adjustments with respect to these demands? Red
knots Calidris canutus winter in coastal areas over a range of latitudes. The
nominal subspecies winters in salty areas in the tropics, whereas the subspecies
Calidris canutus islandica winters in north-temperate regions of comparatively
lower salinities and temperatures. In this study, both subspecies of red knot
were acclimated to different salinity (28/400/00)-temperature (5/35 degrees C)
combinations for 2-week periods. We then measured food/salt intakes, basal
metabolic rate (BMR), body mass and temperature, fat and salt gland scores,
gizzard mass, heat-shock proteins, heterophils/lymphocytes (H/L) ratio and plasma
Na(+) to assess the responses of each taxon to osmoregulatory challenges. High
salinity (HS)-warm-acclimated birds reduced food/salt intake, BMR, body mass, fat
score and gizzard mass, showing that salt/heat loads constrained energy
acquisition rates. Higher salt gland scores in saltier treatments indicated that
its size was adjusted to higher osmoregulatory demands. Elevated plasma Na(+) and
H/L ratio in high-salinity-warm-acclimated birds indicated that salt/heat loads
might have a direct effect on the water-salt balance and stress responses of red
knots. Subspecies had little or no effect on most measured parameters, suggesting
that most adjustments reflect phenotypic flexibility rather than subspecific
adaptations. Our results demonstrate how salinity and temperature affect various
phenotypic traits in a migrant shorebird, highlighting the importance of
considering these factors jointly when evaluating the environmental tolerances of
air-breathing marine taxa.
PMID- 25851407
TI - Eumelanin 3D Architectures: Electrospun PLA Fiber Templating for Mammalian
Pigment Microtube Fabrication.
PMID- 25851409
TI - Effectiveness and safety of a prehospital program of continuous positive airway
pressure (CPAP) in an urban setting - ERRATUM.
PMID- 25851410
TI - Multilayered Thin Films from Boronic Acid-Functional Poly(amido amine)s.
AB - PURPOSE: To investigate the properties of phenylboronic acid-functional
poly(amido amine) polymers (BA-PAA) in forming multilayered thin films with
poly(vinyl alcohol) (PVA) and chondroitin sulfate (ChS), and to evaluate their
compatibility with COS-7 cells. METHODS: Copolymers of phenylboronic acid
functional poly(amido amine)s, differing in the content of primary amine (DAB-BA
PAA) or alcohol (ABOL-BA-PAA) side groups, were synthesized and applied in the
formation of multilayers with PVA and ChS. Biocompatibility of the resulting
films was evaluated through cell culture experiments with COS-7 cells grown on
the films. RESULTS: PVA-based multilayers were thin, reaching ~100 nm at 10
bilayers, whereas ChS-based multilayers were thick, reaching ~600 nm at the same
number of bilayers. All of the multilayers are stable under physiological
conditions in vitro and are responsive to reducing agents, owing to the presence
of disulfide bonds in the polymers. PVA-based films were demonstrated to be
responsive to glucose at physiological pH at the investigated glucose
concentrations (10-100 mM). The multilayered films displayed biocompatibility in
cell culture experiments, promoting attachment and proliferation of COS-7 cells.
CONCLUSIONS: Responsive thin films based on boronic acid functional poly(amido
amine)s are promising biocompatible materials for biomedical applications, such
as drug releasing surfaces on stents or implants. Graphical Abstract Layer-by
Layer Assembly.
PMID- 25851412
TI - Optimized leaf ordering with class labels for hierarchical clustering.
AB - Hierarchical clustering is extensively used in the bioinformatics community to
analyze biomedical data. These data are often tagged with class labels, as e.g.
disease subtypes or gene ontology (GO) terms. Heatmaps in connection with
dendrograms are the common standard to visualize results of hierarchical
clustering. The heatmap can be enriched by an additional color bar at the side,
indicating for each instance in the data set to which class it belongs. In the
ideal case, when the clustering matches perfectly with the classes, one would
expect that instances from the same class cluster together and the color bar
consists of well-separated color blocks without frequent alteration of colors
(classes). But even in the case when instances from the same class cluster
perfectly together, the dendrogram might not reflect this important aspect due to
the fact that its representation is not unique. In this paper, we propose a leaf
ordering algorithm for the dendrogram that preserving the hierarchical clustering
result tries to group instances from the same class together. It is based on the
concept of dynamic programming which can efficiently compute the optimal or
nearly optimal order, consistent with the structure of the tree.
PMID- 25851408
TI - Furan-based benzene mono- and dicarboxylic acid derivatives as multiple
inhibitors of the bacterial Mur ligases (MurC-MurF): experimental and
computational characterization.
AB - Bacterial resistance to the available antibiotic agents underlines an urgent need
for the discovery of novel antibacterial agents. Members of the bacterial Mur
ligase family MurC-MurF involved in the intracellular stages of the bacterial
peptidoglycan biosynthesis have recently emerged as a collection of attractive
targets for novel antibacterial drug design. In this study, we have first
extended the knowledge of the class of furan-based benzene-1,3-dicarboxylic acid
derivatives by first showing a multiple MurC-MurF ligase inhibition for
representatives of the extended series of this class. Steady-state kinetics
studies on the MurD enzyme were performed for compound 1, suggesting a
competitive inhibition with respect to ATP. To the best of our knowledge,
compound 1 represents the first ATP-competitive MurD inhibitor reported to date
with concurrent multiple inhibition of all four Mur ligases (MurC-MurF).
Subsequent molecular dynamic (MD) simulations coupled with interaction energy
calculations were performed for two alternative in silico models of compound 1 in
the UMA/D-Glu- and ATP-binding sites of MurD, identifying binding in the ATP
binding site as energetically more favorable in comparison to the UMA/D-Glu
binding site, which was in agreement with steady-state kinetic data. In the final
stage, based on the obtained MD data novel furan-based benzene monocarboxylic
acid derivatives 8-11, exhibiting multiple Mur ligase (MurC-MurF) inhibition with
predominantly superior ligase inhibition over the original series, were
discovered and for compound 10 it was shown to possess promising antibacterial
activity against S. aureus. These compounds represent novel leads that could by
further optimization pave the way to novel antibacterial agents.
PMID- 25851411
TI - Distinguishing bipolar from unipolar depression: the importance of clinical
symptoms and illness features.
AB - BACKGROUND: Distinguishing bipolar disorder (BP) from major depressive disorder
(MDD) has important relevance for prognosis and treatment. Prior studies have
identified clinical features that differ between these two diseases but have been
limited by heterogeneity and lack of replication. We sought to identify
depression-related features that distinguish BP from MDD in large samples with
replication. METHOD: Using a large, opportunistically ascertained collection of
subjects with BP and MDD we selected 34 depression-related clinical features to
test across the diagnostic categories in an initial discovery dataset consisting
of 1228 subjects (386 BPI, 158 BPII and 684 MDD). Features significantly
associated with BP were tested in an independent sample of 1000 BPI cases and
1000 MDD cases for classifying ability in receiver operating characteristic (ROC)
analysis. RESULTS: Seven clinical features showed significant association with
BPI compared with MDD: delusions, psychomotor retardation, incapacitation,
greater number of mixed symptoms, greater number of episodes, shorter episode
length, and a history of experiencing a high after depression treatment. ROC
analyses of a model including these seven factors showed significant evidence for
discrimination between BPI and MDD in an independent dataset (area under the
curve = 0.83). Only two features (number of mixed symptoms, and feeling high
after an antidepressant) showed an association with BPII versus MDD. CONCLUSIONS:
Our study suggests that clinical features distinguishing depression in BPI versus
MDD have important classification potential for clinical practice, and should
also be incorporated as 'baseline' features in the evaluation of novel diagnostic
biomarkers.
PMID- 25851413
TI - Transforming communication and safety culture in intrapartum care: a multi
organization blueprint.
AB - Effective, patient-centered communication facilitates interception and correction
of potentially harmful conditions and errors. All team members, including women,
their families, physicians, midwives, nurses, and support staff, have roles in
identifying the potential for harm during labor and birth. However, the results
of collaborative research studies conducted by organizations that represent
professionals who care for women during labor and birth indicate that health care
providers may frequently witness, but may not always report, problems with safety
or clinical performance. Some of these health care providers felt resigned to the
continuation of such problems and fearful of retribution if they tried to address
them. Speaking up to address safety and quality concerns is a dynamic social
process. Every team member must feel empowered to speak up about concerns without
fear of put-downs, retribution, or receiving poor-quality care. Patient safety
requires mutual accountability: individuals, teams, health care facilities, and
professional associations have a shared responsibility for creating and
sustaining environments of mutual respect and engaging in highly reliable
perinatal care. Defects in human factors, communication, and leadership have been
the leading contributors to sentinel events in perinatal care for more than a
decade. Organizational commitment and executive leadership are essential to
creating an environment that proactively supports safety and quality. The problem
is well-known; the time for action is now.
PMID- 25851414
TI - Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings.
AB - Recently, mutations in FARS2, which encodes for mitochondrial phenylalanyl-tRNA
synthetase, have been implicated in autosomal recessive combined oxidative
phosphorylation deficiency 14. Associated clinical features in three previously
reported patients with confirmed FARS2 mutations include infantile onset
epilepsy, and a fatal Alpers-like encephalopathy. Herein, we report on two
siblings with global developmental delay, dysarthria and tremor and compound
heterozygous FARS2 abnormalities. They have a heterozygous missense mutation,
c.1255C>T which predicts p.Arg419Cys in exon 7 of FARS2, inherited from their
father and uncovered on exome sequencing, and an interstitial deletion of
chromosome 6p25.1 inherited from their mother and uncovered on SNP array. This
interstitial deletion includes all of exon 6 and parts of introns 5 and 6 of
FARS2. Biochemical studies were also consistent with a mitochondrial disorder.
While these siblings had considerable developmental difficulties, they are making
consistent developmental progress and appear to be considerably less severely
affected than the other patients reported in the literature with FARS2 associated
mitochondrial disease. Thus, this study expands the phenotypic spectrum of FARS2
related disease and emphasizes intragenic deletion in the list of causative
mutations.
PMID- 25851416
TI - Persistence of Phrenic Nerve Palsy Following 28-mm Cryoballoon Ablation: A Four
Year Single Center Experience.
AB - BACKGROUND: Phrenic nerve palsy (PNP) is the most frequently observed
complication in the setting of cryoballoon (CB) ablation (Arctic Front, Medtronic
Inc., Minneapolis, MN, USA). Although, usually transient, resolving before the
end of the procedure, persistent PNP (not resolving before the end of procedure)
can occur. Literature on persistent PNP after second generation CB ablation is
relatively sparse. METHODS: A total of 316 consecutive patients having undergone
large 28-mm CB ablation as index procedure in the Heart Rhythm Management Center,
UZ Brussels, Belgium, from January 2009 to December 2013 were retrospectively
reviewed for the study. Of these 117 patients were treated with the first
generation CB (CB1) and 199 patients with the second generation CB (CB2).
RESULTS: PNP occurred in 10% of the total population. Persistent PNP was only
observed following CB2 ablation which occurred in 4.5% of the group. At a mean
follow-up of 11 months, diaphragmatic contraction in persistent PNP patients
resumed in 78% (7/9) of the patients. In a final follow-up at 5 and 20 months,
PNP persisted in two patients, respectively. PNP during ablation in the right
inferior pulmonary vein was only observed in the CB2 group. No predictors of
persistency of PNP were observed. CONCLUSION: Persistence of PNP only occurred in
the CB2 group in 4.5% of patients. The majority of patients with persistent PNP
were asymptomatic. In most of the patients having persistent PNP after ablation,
complete phrenic nerve function resumed during follow-up (78%).
PMID- 25851417
TI - Conflicts of interest in research: looking out for number one means keeping the
primary interest front and center.
AB - Conflicts of interest represent circumstances in which professional judgments or
actions regarding a primary interest, such as the responsibilities of a medical
researcher, may be at risk of being unduly influenced by a secondary interest,
such as financial gain or career advancement. The secondary interest may be
financial or non-financial, and the resultant bias may be conscious or
unconscious. The presence of conflicts of interest poses a problem for
professional, patient, and public trust in research and the research enterprise.
Effective means of identifying and managing conflicts are an important element in
successfully achieving the goals of research. These strategies typically focus on
the investigator and rely upon disclosure, which has substantial limitations.
Additional management strategies include process-oriented steps and outcomes
oriented strategies. More attention to identifying and managing non-financial
conflicts is needed. Future empirical research will be important for defining
which conflicts need to be better addressed and how to achieve this goal.
PMID- 25851415
TI - Hemophilia B: molecular pathogenesis and mutation analysis.
AB - Hemophilia B is an X-chromosome-linked inherited bleeding disorder primarily
affecting males, but those carrier females with reduced factor IX activity
(FIX:C) levels may also experience some bleeding. Genetic analysis has been
undertaken for hemophilia B since the mid-1980s, through linkage analysis to
track inheritance of an affected allele, and to enable determination of the
familial mutation. Mutation analysis using PCR and Sanger sequencing along with
dosage analysis for detection of large deletions/duplications enables mutation
detection in > 97% of patients with hemophilia B. The risk of the development of
inhibitory antibodies, which are reported in ~ 2% of patients with hemophilia B,
can be predicted, especially in patients with large deletions, and these
individuals are also at risk of anaphylaxis, and nephrotic syndrome if they
receive immune tolerance induction. Inhibitors also occur in patients with
nonsense mutations, occasionally in patients with small insertions/deletions or
splice mutations, and rarely in patients with missense mutations (p.Gln237Lys and
p.Gln241His). Hemophilia B results from several different mechanisms, and those
associated with hemophilia B Leyden, ribosome readthrough of nonsense mutations
and apparently 'silent' changes that do not alter amino acid coding are explored.
Large databases of genetic variants in healthy individuals and patients with a
range of disorders, including hemophilia B, are yielding useful information on
sequence variant frequency to help establish possible variant pathogenicity, and
a growing range of algorithms are available to help predict pathogenicity for
previously unreported variants.
PMID- 25851419
TI - Breakage of two silicone endotracheal tubes during extubation.
AB - Silicone endotracheal tubes broke during tracheal extubation of two dogs after
uneventful anaesthesia. The remaining pieces were removed via endoscopy, and both
dogs recovered with no further problems. A third silicone endotracheal tube broke
while checking for cracks prior to its use. Biofilm formation on the surface of
the endotracheal tube is thought to be the main cause of the breakage.
Destruction of the biofilm is difficult, therefore exhaustive cleaning with
detergents followed by vigorous brushing is recommended to break the interaction
between the silicone surface and the biofilm. It is suggested that careful
attention is paid to how tubes are cleaned and dried (in a hanging position), and
that they are checked carefully for cracks prior to each use.
PMID- 25851420
TI - Dual Element Intercalation into 2D Layered Bi2Se3 Nanoribbons.
AB - We demonstrate the intercalation of multiple zero-valent atomic species into two
dimensional (2D) layered Bi2Se3 nanoribbons. Intercalation is performed
chemically through a stepwise combination of disproportionation redox reactions,
hydrazine reduction, or carbonyl decomposition. Traditional intercalation is
electrochemical thus limiting intercalant guests to a single atomic species. We
show that multiple zero-valent atoms can be intercalated through this chemical
route into the host lattice of a 2D crystal. Intermetallic species exhibit unique
structural ordering demonstrated in a variety of superlattice diffraction
patterns. We believe this method is general and can be used to achieve a wide
variety of new 2D materials previously inaccessible.
PMID- 25851418
TI - Curvature sensing MARCKS-ED peptides bind to membranes in a stereo-independent
manner.
AB - Membrane curvature and lipid composition plays a critical role in interchanging
of matter and energy in cells. Peptide curvature sensors are known to activate
signaling pathways and promote molecular transport across cell membranes.
Recently, the 25-mer MARCKS-ED peptide, which is derived from the effector domain
of the myristoylated alanine-rich C kinase substrate protein, has been reported
to selectively recognize highly curved membrane surfaces. Our previous studies
indicated that the naturally occurring L-MARCKS-ED peptide could simultaneously
detect both phosphatidylserine and curvature. Here, we demonstrate that D-MARCKS
ED, composed by unnatural D-amino acids, has the same activities as its
enantiomer, L-MARCKS-ED, as a curvature and lipid sensor. An atomistic molecular
dynamics simulation suggests that D-MARCKS-ED may change from linear to a boat
conformation upon binding to the membrane. Comparable enhancement of fluorescence
intensity was observed between D- and L-MARCKS-ED peptides, indicating similar
binding affinities. Meanwhile, circular dichroism spectra of D- and L-MARCKS-ED
are almost symmetrical both in the presence and absence of liposomes. These
results suggest similar behavior of artificial D- and natural L-MARCKS-ED
peptides when binding to curved membranes. Our studies may contribute to further
understanding of how MARCKS-ED senses membrane curvature as well as provide a new
direction to develop novel membrane curvature probes.
PMID- 25851422
TI - Erratum.
PMID- 25851421
TI - Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: Evidence
from randomised controlled trials.
AB - SCOPE: Cruciferous-rich diets have been associated with reduction in plasma LDL
cholesterol (LDL-C), which may be due to the action of isothiocyanates derived
from glucosinolates that accumulate in these vegetables. This study tests the
hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce
plasma LDL-C. METHODS AND RESULTS: One hundred and thirty volunteers were
recruited to two independent double-blind, randomly allocated parallel dietary
intervention studies, and were assigned to consume either 400 g standard broccoli
or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before
and after the intervention. In study 1 (37 volunteers), the HG broccoli diet
reduced plasma LDL-C by 7.1% (95% CI: -1.8%, -12.3%, p = 0.011), whereas standard
broccoli reduced LDL-C by 1.8% (95% CI +3.9%, -7.5%, ns). In study 2 (93
volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: -2.1%,
-8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI:
+0.8%, -5.7%, ns). When data from the two studies were combined the reduction in
LDL-C by the HG broccoli was significantly greater than standard broccoli (p =
0.031). CONCLUSION: Evidence from two independent human studies indicates that
consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C.
PMID- 25851423
TI - Intraoperative acupuncture for posttonsillectomy pain: a randomized, double
blind, placebo-controlled trial.
AB - OBJECTIVES/HYPOTHESIS: To evaluate the effect of intraoperative acupuncture on
posttonsillectomy pain in the pediatric population. STUDY DESIGN: Prospective,
double-blind, randomized, placebo-controlled trial. METHODS: Patients aged 3 to
12 years undergoing tonsillectomy were recruited at a tertiary children's
hospital between February 2011 and May 2012. Participants were block-randomized
to receive acupuncture or sham acupuncture during anesthesia for tonsillectomy.
Surgeons, staff, and parents were blinded from treatment. Tonsillectomy was
performed by one of two surgeons using a standard technique (monopolar cautery),
and a single anesthetic protocol was followed. Study endpoints included time
spent in the postanesthesia care unit, the amount of opioids administered in the
perioperative period, and pain measures and presence of nausea/vomiting from
postoperative home surveys. RESULTS: Fifty-nine children aged 3 to 12 years were
randomized to receive acupuncture (n = 30) or sham acupuncture (n = 29). No
significant demographic differences were noted between the two cohorts.
Perioperative data were recorded for all patients; 73% of patients later returned
home surveys. There were no significant differences in the amount of opioid
medications administered or total postanesthesia care unit time between the two
cohorts. Home surveys of patients but not of parents revealed significant
improvements in pain control in the acupuncture treatment-group postoperatively
(P = 0.0065 and 0.051, respectively), and oral intake improved significantly
earlier in the acupuncture treatment group (P = 0.01). No adverse effects of
acupuncture were reported. CONCLUSIONS: This study demonstrates that
intraoperative acupuncture is feasible, well tolerated, and results in improved
pain and earlier return of diet postoperatively. LEVEL OF EVIDENCE: 1b.
PMID- 25851424
TI - Epidemiology of superficial mycoses in Northern Greece: a 4-year study.
AB - BACKGROUND: Superficial mycoses are defined as the fungal infections of skin,
hair or nails that are caused by dermatophytes, yeasts and non-dermatophytic
moulds. Dermatophytes are the most frequently isolated fungi from specimens of
patients with superficial mycoses. OBJECTIVE: Studying the possible alteration of
the epidemiology of superficial mycoses in Northern Greece during the last two to
three decades. MATERIALS AND METHODS: Data concerning the superficial mycoses
from patients coming mainly from the region of Macedonia, Northern Greece,
between January 2010 and January 2014 were recorded and analysed. They included
specimens from 438 patients (146 M/292 F), within an age range of 2-85 years old.
503 samples were collected from skin (81, 16.1%), hair (18, 3.6%) and nails
(fingernails 84, 16.7%, toenails 320, 63.6%) lesions. RESULTS: Of a total of 222
positive cultures, 50 were considered as yielding clinically non-significant
isolates (saprophytes). Among the rest (172), dermatophytes were the most
prevalent isolates (102, 59.3%), followed by yeasts (51, 29.7%) and non
dermatophytic moulds (19, 11%). Trichophyton rubrum (55, 53.9%), Trichophyton
mentagrophytes (18, 17.6%) and Microsporum canis (23, 22.5%) were the most common
isolates among dermatophytes (total = 102). Candida parapsilosis (26, 51%), and
Candida albicans (10, 19.6%) among yeasts (total = 51) whereas Fusarium (6,
31.6%) and Acremonium species (3, 15.8%) among the non-dermatophytic moulds
(total=19). CONCLUSION: Compared to previous studies from Northern Greece, the
epidemiology of superficial mycoses in the specific geographic region seems not
to have been altered the last two to three decades.
PMID- 25851425
TI - Post-meal perceivable satiety and subsequent energy intake with intake of
partially hydrolysed guar gum.
AB - Partially hydrolysed guar gum (PHGG), a soluble dietary fibre, has been shown to
provide many health benefits. Previous studies had suggested that the combination
of PHGG with protein provided a significant satiation effect on visual analogue
scales (VAS). What was lacking was only the effect of administration of small
doses of PHGG on post-meal satiation and subsequent energy intake. The objectives
of the present investigations were to find the subjective perception of post-meal
satiety with acute and long term administration of small amounts of PHGG alone
with food, its effects on subsequent energy intake and the comparative effects
among different types of soluble fibres. The following three separate studies
were conducted: in study 1, healthy subjects (n 12) consumed PHGG along with
breakfast, lunch and an evening snack; in study 2, healthy subjects (n 24)
consumed 2 g of PHGG or dextrin along with yogurt as breakfast for 2 weeks; in
study 3, healthy subjects (n 6) took 6 g each of either PHGG or indigestible
dextrin or inulin along with lunch. In all the studies, various satiety
parameters were measured on VAS before and after consumption of PHGG. The
addition of PHGG showed significant (P < 0.05) acute (studies 1 and 3) and long
term (studies 1 and 2) satiety effects compared to the control and/or an equal
amount of carbohydrate or other types of soluble fibre. Study 2 also indicated
that the prolonged consumption of PHGG may significantly (P < 0.05) reduce energy
intake from whole-day snacking. PHGG could be an ideal natural soluble fibre for
delivering acute and long term satiety effects for comfortable appetite control.
PMID- 25851426
TI - Condensed lignin structures and re-localization achieved at high severities in
autohydrolysis of Eucalyptus globulus wood and their relationship with cellulose
accessibility.
AB - Eucalyptus globulus wood was subjected to autohydrolysis pretreatment at
different severity factors. The pretreated materials were enzymatically
saccharified at a substrate load of 10% (w/v) using a cellulase enzyme complex.
Around 82-95% of original glucans were retained in the pretreated material, and
the enzymatic hydrolysis yields ranged from 58% to 90%. The chemical and
structural changes in the pretreated materials were investigated by microscopic
(SEM, LSCM) and spectroscopic (2D-HSQC NMR and FT-IR) techniques. 2D-NMR results
showed a reduction in the amounts of beta-O-4 aryl-ether linkages and suggested
the presence of newly condensed structures of lignin in the biomass pretreated at
the more severe conditions. Furthermore, the microscopic analysis showed that
lignin migrates out of the cell wall and re-deposits in certain regions of the
fibers at the more severe conditions to form droplet-like structures and expose
the cellulose surface. These changes improved the glucose yield up to 69%, on dry
wood basis.
PMID- 25851427
TI - Organisational interventions for improving wellbeing and reducing work-related
stress in teachers.
AB - BACKGROUND: The teaching profession is an occupation with a high prevalence of
work-related stress. This may lead to sustained physical and mental health
problems in teachers. It can also negatively affect the health, wellbeing and
educational attainment of children, and impose a financial burden on the public
budget in terms of teacher turnover and sickness absence. Most evaluated
interventions for the wellbeing of teachers are directed at the individual level,
and so do not tackle the causes of stress in the workplace. Organisational-level
interventions are a potential avenue in this regard. OBJECTIVES: To evaluate the
effectiveness of organisational interventions for improving wellbeing and
reducing work-related stress in teachers. SEARCH METHODS: We searched the
Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
PsycINFO, ASSIA, AEI, BEI, BiblioMap, DARE, DER, ERIC, IBSS, SSCI, Sociological
Abstracts, a number of specialist occupational health databases, and a number of
trial registers and grey literature sources from the inception of each database
until January 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs),
cluster-RCTs, and controlled before-and-after studies of organisational-level
interventions for the wellbeing of teachers. DATA COLLECTION AND ANALYSIS: We
used standard methodological procedures expected by Cochrane. MAIN RESULTS: Four
studies met the inclusion criteria. They were three cluster-randomised controlled
trials and one with a stepped-wedge design.Changing task characteristicsOne study
with 961 teachers in eight schools compared a task-based organisational change
intervention along with stress management training to no intervention. It found a
small reduction at 12 months in 10 out of 14 of the subscales in the Occupational
Stress Inventory, with a mean difference (MD) varying from -3.84 to 0.13, and a
small increase in the Work Ability Index (MD 2.27; 95% confidence interval (CI)
1.64 to 2.90; 708 participants, low-quality evidence).Changing organisational
characteristicsTwo studies compared teacher training combined with school-wide
coaching support to no intervention. One study with 59 teachers in 43 schools
found no significant effects on job-related anxiety (MD -0.25 95% CI -0.61 to
0.11, very low-quality evidence) or depression (MD -0.26 95% CI -0.57 to 0.05,
very low-quality evidence) after 24 months. The other study with 77 teachers in
18 schools found no significant effects on the Maslach Burnout Inventory
subscales (e.g. emotional exhaustion subscale: MD -0.05 95% CI -0.52 to 0.42, low
quality evidence) or the Teacher Perceived Emotional Ability subscales (e.g.
regulating emotions subscale: MD 0.11 95% CI -0.11 to 0.33, low-quality evidence)
after six months.Multi-component interventionOne study with 1102 teachers in 34
schools compared a multi-component intervention containing performance bonus, job
promotion opportunities and mentoring support to a matched-comparison group
consisting of 300 schools. It found moderately higher teacher retention rates (MD
11.50 95% CI 3.25 to 19.75 at 36 months follow-up, very low-quality evidence).
However, the authors reported results only from one cohort out of four (eight
schools), demonstrating a high risk of reporting bias. AUTHORS' CONCLUSIONS: We
found low-quality evidence that organisational interventions lead to improvements
in teacher wellbeing and retention rates. We need further evaluation of the
effects of organisational interventions for teacher wellbeing. These studies
should follow a complex-interventions framework, use a cluster-randomised design
and have large sample sizes.
PMID- 25851428
TI - Invited editorial: zoonotic lymphatic filariasis in the Americas: trends in
epidemiology, diagnosis and treatment, with special emphasis on brugian
filariasis.
PMID- 25851429
TI - Human anthrax as a re-emerging disease.
AB - Anthrax is primarily a disease of herbivores and the etiological agent is B.
anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped
bacterium. Bacillus anthracis spores are highly resistant to heat, pressure,
ultraviolet and ionizing radiation, chemical agents and disinfectants. For these
reasons, B. anthracis spores are an attractive choice as biological agents for
the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the
infectious agent. The disease most commonly affects wild and domestic mammals.
Human are secondarily infected by contact with infected animals and contaminated
animal products or directly expose to B. anthracis spores. Anthrax occurs
worldwide. This infection is still endemic or hyperendemic in both animals and
humans in some part of areas of the world; particularly in Middle East, West
Africa, Central Asia, some part of India, South America. However, some countries
are claiming free of anthrax, and anthrax has become a re-emerging disease in
western countries with the intentional outbreak. Currently, anthrax is classified
according to its setting as (1) naturally occurring anthrax, (2) bioterrorism
related anthrax. Vast majority of human anthrax are occurring as naturally
occurring anthrax in the world. It is also a threaten disease for western
countries. The aim of this paper is to review the relevant patents, short
historical perspective, microbiological and epidemiological features, clinical
presentations and treatment.
PMID- 25851430
TI - Brucellosis and its particularities in children travelers.
AB - Brucellosis is still endemic in many countries in the world, however, having a
significantly higher incidence in developing countries. As consequence of travel,
risk for children from non-endemic areas would be considerable when visiting
developing countries. Then, the purpose of this review is to provide, after a
bibliographical search, an update on the main aspects of this disease in the
traveler children. For the general practitioner, but particularly for travel
medicine practitioner and pediatricians, these clinicoepidemiological
considerations should be taken in mind in the differential diagnosis when
assessing children returning from travel to brucellosis endemic areas.
PMID- 25851431
TI - Shape-tailored colloidal molecules obtained by self-assembly of model gold
nanoparticles with flexible polyelectrolyte.
AB - We study for the first time the structure of stable finite size clusters (i.e.,
colloidal molecules) obtained by self-assembly of cationic gold nanoparticles
(i.e., atoms) mediated by a flexible polyanion. We reveal with nondenaturizing
techniques a striking structural transition from 1D small chains of 12 gold
nanoparticles (AuNPs) with a self-avoiding conformation to 3D fractal clusters of
130 AuNPs with short-range ordering around the charge inversion threshold.
Interestingly, these well-defined structures are obtained by simple mixing in
water without anisotropic functionalization or external forces. As a preliminary
step, we introduce a new synthesis pathway leading to well-defined cationic AuNPs
of controllable size that can be dispersed in H2O or D2O without aggregation and
ligands' self-assemblies. On this occasion, we point for the first time that
usual procedures do not enable to eliminate cationic ligands' self-assemblies
that could play an undesired role in AuNPs' self-assembly through electrostatic
interactions.
PMID- 25851432
TI - Prostatic arterial embolization for the treatment of lower urinary tract symptoms
caused by benign prostatic hyperplasia: a comparative study of medium- and large
volume prostates.
AB - OBJECTIVES: To compare the outcomes of prostatic arterial embolization (PAE) in
treating large (>80 mL) in comparison with medium-sized prostate glands (50-80
mL) to determine whether size affects the outcome of PAE. PATIENTS AND METHODS: A
total of 115 patients (mean age 71.5 years) diagnosed with lower urinary tract
symptoms (LUTS) attributable to benign prostatic hyperplasia (BPH) refractory to
medical treatment underwent PAE. Group A (n = 64) included patients with a mean
prostate volume of 129 mL; group B (n = 51) included patients with a mean
prostate volume of 64 mL. PAE was performed using 100-MUm particles. Follow-up
was performed using the International Prostate Symptom Score (IPSS), quality of
life (QoL), peak urinary flow rate (Qmax ), post-void residual urine volume
(PVR), the International Index of Erectile Function short form (IIEF-5), prostate
specific antigen (PSA) and prostate volume measured by magnetic resonance imaging
at 1, 3 and 6 months, and every 6 months thereafter. RESULTS: There were no
significant differences between groups in baseline IPSS, QoL, Qmax , PVR, PSA
level or IIEF-5 score. The technical success rate was 93.8% in group A and 96.8%
in group B (P = 0.7). A total of 101 patients (55 patients in group A and 46
patients in group B) completed the mean (range) follow-up of 17 (12-33) months.
Compared with baseline, there were significant improvements in IPSS, QoL, Qmax ,
prostate volume and PVR in both groups after PAE. The outcomes in group A were
significantly better than in group B with regard to mean +/- sd IPSS (-14 +/- 6.5
vs -10.5 +/- 5.5, respectively), Qmax (6.0 +/- 1.5 vs 4.5 +/- 1.0 mL/s,
respectively), PVR (-80.0 +/- 25.0 vs -60.0 +/- 20.0 mL, respectively), prostate
volume (-54.5 +/- 18.0 mL [-42.3%] vs -18.5 +/- 5.0 mL [-28.9%], respectively),
and QoL score (-3.0 +/- 1.5 vs -2.0 +/- 1.0) with P values <0.05. The mean IIEF-5
score was not significantly different from baseline in both groups. No major
complications were noted. CONCLUSIONS: We found that PAE is a safe and effective
treatment method for patients with LUTS attributable to BPH. The clinical and
imaging outcomes of PAE were better in patients with larger prostate glands than
medium-sized ones.
PMID- 25851434
TI - Richard Dronskowski.
AB - "My "science heroes" are Otto Hahn and Hans Hellmann. My favorite authors are
Walter Kempowski and John Updike ...?" This and more about Richard Dronskowski
can be found on page 8872.
PMID- 25851433
TI - Treatment of peri-implant mucositis using a glycine powder air-polishing or
ultrasonic device: a randomized clinical trial.
AB - AIM: To evaluate the clinical treatment effects of a glycine powder air-polishing
or ultrasonic device on peri-implant mucositis. MATERIALS AND METHODS: Thirty
seven patients with one implant diagnosed with peri-implant mucositis (probing
depth >=4 mm (0.2N) and bleeding on probing (BOP) (primary outcome)) were
randomly assigned to treatment with either glycine powder air-polishing (GPAP) or
ultrasonic (US) debridement. Treatment was performed at baseline and at 3 and 6
months. Professional supra gingival cleaning was performed at 9 and 12 months.
Oral hygiene instructions were reinforced at each visit. RESULTS: At 12 months
there was a statistically significant reduction in mean plaque score, bleeding on
probing and number of periodontal pockets >=4 mm within the treatment groups
compared to baseline. The percentages of diseased sites were significantly
reduced for both groups. CONCLUSIONS: Treatment with a glycine powder air
polishing or an ultrasonic device is effective in non-surgical treatment of peri
implant mucositis.
PMID- 25851435
TI - Sleep disordered breathing in patients with Prader-Willi syndrome: A multicenter
study.
AB - OBJECTIVES: Sleep disordered breathing (SDB) is common in patients with Prader
Willi syndrome (PWS) and systematic screening is recommended, especially before
growth hormone treatment. The aim of the study was to describe the baseline SDB
and therapeutic interventions in a large cohort of patients. STUDY DESIGN:
Retrospective study. SUBJECT SELECTION: Eighty-eight patients with PWS, median
[interquartile range] age of 5.1 [1.0-14.5] years old (range 0.3-44.3), who were
followed in three centers (France, Italy). METHODOLOGY: Anthropometrics,
polygraphy (PG), and gas exchange data were analyzed. RESULTS: Median body mass
index (BMI) was 20 [16-34] kg/m(2), BMI z-score for patients aged 2-20 years old
was 2.1 [1.2-2.8] SD, mixed-obstructive apnea-hypopnea index (MOAHI) 1.8 [0.6
5.0] events/hr, and central apnea index (CAI) 0.1 [0.0-0.6] events/hr. Minimum
pulse oximetry (SpO2) was 88 [84-91]%, percentage of time with SpO2 <90% 0.1 [0.0
1.0]%, and oxygen desaturation index 2 [1-4]/hr. An apnea-hypopnea index (AHI) >=
1.5 and >= 5 events/hr was observed in 53% of children and 41% of adults,
respectively. No correlations were observed between MOAHI and anthropometrics
data (age, BMI, BMI z-score), while MOAHI significantly correlated with SpO2
indexes. Age and BMI only weakly correlated with SpO2 indexes. Growth hormone
could be initiated in 48 patients. Regarding post-PG therapy, 9 patients had
upper airway surgery, and noninvasive CPAP/bilevel ventilation was started in 16
patients. CONCLUSIONS: Patients with PWS exhibit a high prevalence of SDB. The
lack of association between obesity and SDB leads to hypothesize that hypotonia
and/or facial dysmorphic features may play a major role in the occurrence of SDB.
PMID- 25851437
TI - Menstrual cycle, sex hormones in female inflammatory bowel disease patients with
and without surgery.
AB - Healthy women at reproductive age experience a cyclical alteration of
gastrointestinal (GI) symptomatology during their menstrual cycle. Additionally,
the majority of healthy women also complain of worsening of GI symptoms either
during the premenstrual or menstrual phase. Despite conflicting evidence, studies
suggest that sex hormones may increase GI transit time during the luteal phase.
Similar phenomenon is also observed in women with underlying inflammatory bowel
disease (IBD). The mechanism underlying this complex pathophysiology is still not
completely understood. However, a possible influence of sex hormones on the brain
gut-microbiota axis is hypothesized. The diagnosis of IBD is associated with a
delay in menarche as well as menstrual function irregularities including
alterations in cycle length and the duration of flow. There is little data on the
effect of menopause on IBD disease activity and conflicting data on the effect of
IBD diagnosis on the onset of menopause. The role of contraceptives and hormone
replacement therapies on the development or disease activity of IBD has not been
yet established. Moreover, IBD patients with concomitant dysmenorrhea report
heightened pain during menses. The effect of non-steroidal anti-inflammatory
drugs in treating primary dysmenorrhea on the disease course of IBD is unknown.
In addition, the effect of IBD medications including immunomodulators and
biologics on menstrual function remains unclear. Also, the role of IBD surgery on
menstrual irregularities needs to be fully elucidated. Hence, understanding the
influence of menstrual function on IBD disease activity and vice versa and the
maintenance of normal menstrual function in those patients is important in
improving overall reproductive health and fertility and outcome of IBD.
PMID- 25851436
TI - Deformability in the cleavage site of primary microRNA is not sensed by the
double-stranded RNA binding domains in the microprocessor component DGCR8.
AB - The prevalence of double-stranded RNA (dsRNA) in eukaryotic cells has only
recently been appreciated. Of interest here, RNA silencing begins with dsRNA
substrates that are bound by the dsRNA-binding domains (dsRBDs) of their
processing proteins. Specifically, processing of microRNA (miRNA) in the nucleus
minimally requires the enzyme Drosha and its dsRBD-containing cofactor protein,
DGCR8. The smallest recombinant construct of DGCR8 that is sufficient for in
vitro dsRNA binding, referred to as DGCR8-Core, consists of its two dsRBDs and a
C-terminal tail. As dsRBDs rarely recognize the nucleotide sequence of dsRNA, it
is reasonable to hypothesize that DGCR8 function is dependent on the recognition
of specific structural features in the miRNA precursor. Previously, we
demonstrated that noncanonical structural elements that promote RNA flexibility
within the stem of miRNA precursors are necessary for efficient in vitro cleavage
by reconstituted Microprocessor complexes. Here, we combine gel shift assays with
in vitro processing assays to demonstrate that neither the N-terminal dsRBD of
DGCR8 in isolation nor the DGCR8-Core construct is sensitive to the presence of
noncanonical structural elements within the stem of miRNA precursors, or to
single-stranded segments flanking the stem. Extending DGCR8-Core to include an N
terminal heme-binding region does not change our conclusions. Thus, our data
suggest that although the DGCR8-Core region is necessary for dsRNA binding and
recruitment to the Microprocessor, it is not sufficient to establish the
previously observed connection between RNA flexibility and processing efficiency.
PMID- 25851438
TI - Model-based standardization to adjust for unmeasured cluster-level confounders
with complex survey data.
AB - Model-based standardization uses a statistical model to estimate a standardized,
or unconfounded, population-averaged effect. With it, one can compare groups had
the distribution of confounders been identical in both groups to that of the
standard population. We develop two methods for model-based standardization with
complex survey data that accommodate a categorical confounder that clusters the
individual observations into a very large number of subgroups. The first method
combines a random-intercept generalized linear mixed model with a conditional
pseudo-likelihood estimator of the fixed effects. The second method combines a
between-within generalized linear mixed model with census data on the cluster
level means of the individual-level covariates. We conduct simulation studies to
compare the two approaches. We apply the two methods to the 2008 Florida
Behavioral Risk Factor Surveillance System survey data to estimate standardized
proportions of people who drink alcohol, within age groups, adjusting for
measured individual-level and unmeasured cluster-level confounders.
PMID- 25851439
TI - Investigation of the use of aerobic granules for the treatment of sugar beet
processing wastewater.
AB - The treatment of sugar beet processing wastewater in aerobic granular sequencing
batch reactor (SBR) was examined in terms of chemical oxygen demand (COD) and
nitrogen removal efficiency. The effect of sugar beet processing wastewater of
high solid content, namely 2255 +/- 250 mg/L total suspended solids (TSS), on
granular sludge was also investigated. Aerobic granular SBR initially operated
with the effluent of anaerobic digester treating sugar beet processing wastewater
(Part I) achieved average removal efficiencies of 71 +/- 30% total COD (tCOD), 90
+/- 3% total ammonifiable nitrogen (TAN), 76 +/- 24% soluble COD (sCOD) and 29 +/
4% of TSS. SBR was further operated with sugar beet processing wastewater (Part
II), where the tCOD, TAN, sCOD and TSS removal efficiencies were 65 +/- 5%, 61 +/
4%, 87 +/- 1% and 58 +/- 10%, respectively. This study indicated the
applicability of aerobic granular SBRs for the treatment of both sugar beet
processing wastewater and anaerobically digested processing wastewater. For
higher solids removal, further treatment such as a sedimentation tank is required
following the aerobic granular systems treating solid-rich wastewaters such as
sugar beet processing wastewater. It was also revealed that the application of
raw sugar beet processing wastewater slightly changed the aerobic granular sludge
properties such as size, structure, colour, settleability and extracellular
polymeric substance content, without any drastic and negative effect on treatment
performance.
PMID- 25851440
TI - A common case with common problems: laparoscopic treatment of small bowel
obstruction (SBO).
AB - BACKGROUND: Laparoscopic approach to patients with suspected small bowel
obstruction (SBO) is not yet widely accepted nor clearly standardized; due to the
absence of randomized trials, many questions still remain matter of debate.
METHODS: By describing a single typical case of acute intestinal occlusive
syndrome in a 82 years old woman, in which a SBO was suspected on the basis of
previous surgical history and CT scan imaging, every single step of therapy is
discussed, including the decision to perform explorative laparoscopy, the first
trocar placement, the decision to continue by laparoscopy or to convert in
laparotomy, and finally the small bowel resection and re-anastomosis. RESULTS:
The decision to approach a suspected SBO by laparoscopy should be taken on the
basis of a number of features which would predict the success rate, such as mild
abdominal distention, proximal obstruction, partial obstruction, small bowel
diameter less than 4 cm, previous appendenctomy, anticipated single band
adhesion. In these cases laparoscopic approach may improve post-operative
outcomes in terms of reduced postoperative ileus, hospitalization and wound
infection rate. CONCLUSIONS: In selected, not unusual cases of SBO, a
laparoscopic approach is feasible and effective. A growing Literature, mainly
based upon retrospective series, is available. KEY WORDS: Conversion,
Laparoscopy, Mortality, Small bowel obstruction, Surgery.
PMID- 25851441
TI - Tight junction disruption by cadmium in an in vitro human airway tissue model.
AB - BACKGROUND: The cadmium (Cd) present in air pollutants and cigarette smoke has
the potential of causing multiple adverse health outcomes involving damage to
pulmonary and cardiovascular tissue. Injury to pulmonary epithelium may include
alterations in tight junction (TJ) integrity, resulting in impaired epithelial
barrier function and enhanced penetration of chemicals and biomolecules. Herein,
we investigated mechanisms involved in the disruption of TJ integrity by Cd
exposure using an in vitro human air-liquid-interface (ALI) airway tissue model
derived from normal primary human bronchial epithelial cells. METHODS: ALI
cultures were exposed to noncytotoxic doses of CdCl2 basolaterally and TJ
integrity was measured by Trans-Epithelial Electrical Resistance (TEER) and
immunofluorescence staining with TJ markers. PCR array analysis was used to
identify genes involved with TJ collapse. To explore the involvement of kinase
signaling pathways, cultures were treated with CdCl2 in the presence of kinase
inhibitors specific for cellular Src or Protein Kinase C (PKC). RESULTS:
Noncytotoxic doses of CdCl2 resulted in the collapse of barrier function, as
demonstrated by TEER measurements and Zonula occludens-1 (ZO-1) and occludin
staining. CdCl2 exposure altered the expression of several groups of genes
encoding proteins involved in TJ homeostasis. In particular, down-regulation of
select junction-interacting proteins suggested that a possible mechanism for Cd
toxicity involves disruption of the peripheral junctional complexes implicated in
connecting membrane-bound TJ components to the actin cytoskeleton. Inhibition of
kinase signaling using inhibitors specific for cellular Src or PKC preserved the
integrity of TJs, possibly by preventing occludin tyrosine hyperphosphorylation,
rather than reversing the down-regulation of the junction-interacting proteins.
CONCLUSIONS: Our findings indicate that acute doses of Cd likely disrupt TJ
integrity in human ALI airway cultures both through occludin hyperphosphorylation
via kinase activation and by direct disruption of the junction-interacting
complex.
PMID- 25851442
TI - Tillage Management and Seasonal Effects on Denitrifier Community Abundance, Gene
Expression and Structure over Winter.
AB - Tillage effects on denitrifier communities and nitrous oxide (N2O) emissions were
mainly studied during the growing season. There is limited information for the
non-growing season, especially in northern countries where winter has prolonged
periods with sub-zero temperatures. The abundance and structure of the
denitrifier community, denitrification gene expression and N2O emissions in
fields under long-term tillage regimes [no-tillage (NT) vs conventional tillage
(CT)] were assessed during two consecutive winters. NT exerted a positive effect
on nirK and nosZ denitrifier abundance in both winters compared to CT. Moreover,
the two contrasting managements had an opposite influence on nirK and nirS
RNA/DNA ratios. Tillage management resulted in different denitrifier community
structures during both winters. Seasonal changes were observed in the abundance
and the structure of denitrifiers. Interestingly, the RNA/DNA ratios were greater
in the coldest months for nirK, nirS and nosZ. N2O emissions were not influenced
by management but changed over time with two orders of magnitude increase in the
coldest month of both winters. In winter of 2009-2010, emissions were mainly as
N2O, whereas in 2010-2011, when soil temperatures were milder due to persistent
snow cover, most emissions were as dinitrogen. Results indicated that tillage
management during the growing season induced differences in denitrifier community
structure that persisted during winter. However, management did not affect the
active cold-adapted community structure.
PMID- 25851443
TI - Picophytoplankton as Tracers of Environmental Forcing in a Tropical Monsoonal
Bay.
AB - In order to better understand the picophytoplankton (PP) dynamics in tropical
monsoon influenced coastal regions, samples were collected daily (June-September
2008: monsoon, December 2008: post-monsoon and April 2009: pre-monsoon) from a
fixed station in Dona Paula Bay, India. Eight PP abundance peaks comprising
Prochlorococcus-like cells, picoeukaryotes, and three groups of Synechococcus
occurred. The chlorophyll biomass and PP abundance were negatively influenced by
reduced solar radiation, salinity and water transparency due to precipitation and
positively influenced by the stabilized waters during precipitation break/non
monsoon periods. Responses to environmental conditions differed with PP groups,
wherein the presence of Synechococcus-PEI (phycoerythrin) throughout the year
suggested its ability to tolerate salinity and temperature variations and low
light conditions. Synechococcus-PEII appearance toward monsoon end and non
monsoon during high water transparency suggests its tidal advection from offshore
waters. Dominance of Synechococcus-PC (phycocyanin) at intermediate salinities
under low water transparency during MON and high salinities in PrM coinciding
with high nitrate concentrations implies a greater influence of light quality or
nutrients. Cyanobacteria and not picoeukaryotes were the dominant
picophytoplankton in terms of numbers as well as biomass. This study suggests
that PP could be used as tracers of environmental forcing driven by tides and
freshwater influx and also highlights the importance of high-frequency samplings
in dynamic coastal regions through which transient responses can be captured.
PMID- 25851444
TI - Diversity and Ecological Characterization of Sporulating Higher Filamentous
Marine Fungi Associated with Spartina maritima (Curtis) Fernald in Two Portuguese
Salt Marshes.
AB - Fungal communities associated with early stages of decomposition of Spartina
maritima (Curtis) Fernald were assessed in two geographically distinct salt
marshes in Portugal by direct observation of fungal sporulating structures.
Twenty-three fungal taxa were identified from 390 plant samples, 11 of which were
common to both study sites. Natantispora retorquens, Byssothecium obiones,
Phaeosphaeria spartinicola, Phoma sp. 1 and Stagonospora sp. were the most
frequent fungal taxa in the studied communities. The fungal species Anthostomella
spissitecta, Camarosporium roumeguerii, Coniothyrium obiones, Decorospora
gaudefroyi, Halosarpheia trullifera, Leptosphaeria marina and Stagonospora
haliclysta were recorded for the first time on S. maritima plants; with the
exception of C. roumeguerii and L. marina, all of these species were also new
records for Portugal. The differences between species composition of the
communities associated with S. maritima were attributed to differences in abiotic
conditions of the salt marshes. Although the fungal taxa were distributed
differently along the host plants, common species to both fungal communities were
found on the same relative position, e.g. B. obiones, Lulworthia sp. and N.
retorquens occurred on the basal plant portions, Buergenerula spartinae,
Dictyosporium pelagicum and Phoma sp. 1 on the middle plant portions and P.
spartinicola and Stagonospora sp. on the top plant portions. The distinct
vertical distribution patterns reflected species-specific salinity requirements
and flooding tolerance, but specially substrate preferences. The most frequent
fungi in both communities also exhibited wider distribution ranges and produced a
higher number of fruiting structures, suggesting a more active key role in the
decay process of S. maritima.
PMID- 25851445
TI - Temporal Dynamics of Active Prokaryotic Nitrifiers and Archaeal Communities from
River to Sea.
AB - To test if different niches for potential nitrifiers exist in estuarine systems,
we assessed by pyrosequencing the diversity of archaeal gene transcript markers
for taxonomy (16S ribosomal RNA (rRNA)) during an entire year along a salinity
gradient in surface waters of the Charente estuary (Atlantic coast, France). We
further investigated the potential for estuarine prokaryotes to oxidize ammonia
and hydrolyze urea by quantifying thaumarchaeal amoA and ureC and bacterial amoA
transcripts. Our results showed a succession of different nitrifiers from river
to sea with bacterial amoA transcripts dominating in the freshwater station while
archaeal transcripts were predominant in the marine station. The 16S rRNA
sequence analysis revealed that Thaumarchaeota marine group I (MGI) were the most
abundant overall but other archaeal groups like Methanosaeta were also
potentially active in winter (December-March) and Euryarchaeota marine group II
(MGII) were dominant in seawater in summer (April-August). Each station also
contained different Thaumarchaeota MGI phylogenetic clusters, and the clusters'
microdiversity was associated to specific environmental conditions suggesting the
presence of ecotypes adapted to distinct ecological niches. The amoA and ureC
transcript dynamics further indicated that some of the Thaumarchaeota MGI
subclusters were involved in ammonia oxidation through the hydrolysis of urea.
Our findings show that ammonia-oxidizing Archaea and Bacteria were adapted to
contrasted conditions and that the Thaumarchaeota MGI diversity probably
corresponds to distinct metabolisms or life strategies.
PMID- 25851446
TI - Changes in the Synechococcus Assemblage Composition at the Surface of the East
China Sea Due to Flooding of the Changjiang River.
AB - The aim of this study was to elucidate how flooding of the Changjiang River
affects the assemblage composition of phycoerythrin-rich (PE-rich) Synechococcus
at the surface of the East China Sea (ECS). During non-flooding summers (e.g.,
2009), PE-rich Synechococcus usually thrive at the outer edge of the Changjiang
River diluted water coverage (CDW; salinity <=31 PSU). In the summer of 2010, a
severe flood occurred in the Changjiang River basin. The plentiful freshwater
injection resulted in the expansion of the CDW over half of the ECS and caused PE
rich cells to show a uniform distribution pattern, with decreased abundance
compared with the non-flooding summer. The phylogenetic diversity of 16S rRNA
gene sequences indicated that the flooding event also shifted the picoplankton
community composition from being dominated by Synechococcus, mainly attributed to
the clade II lineage, to various orders of heterotrophic bacteria, including
Actinobacteria, Flavobacteria, alpha-Proteobacteria, and gamma-Proteobacteria. As
an increasing number of studies have proposed that global warming might result in
more frequent floods, combining this perspective with the information obtained
from our previous [1] and this studies yield a more comprehensive understanding
of the relationship between the composition of the marine Synechococcus
assemblage and global environmental changes.
PMID- 25851447
TI - A cutaneous lesion.
PMID- 25851448
TI - Antiphospholipid syndrome: an update.
AB - BACKGROUND: Antiphospholipid syndrome (APS) or 'Hughes syndrome' is a
prothrombotic disease characterized by thrombosis and pregnancy morbidity in the
presence of antiphospholipid antibodies (aPL). More than three decades have
passed, and experts are still uncovering new pieces of this disease complex
pathogenesis and management. MATERIALS AND METHODS: We searched in literature
using MEDLINE and PubMed databases focusing on the latest development on disease
pathogenesis, risk assessment of thrombosis and treatment of APS. RESULTS: The
phosphatidylinositol 3-kinase (PI3K)-AKT-mTORC pathway was most recently
identified to have a crucial role in activating inflammation among endothelial
vessel wall causing vascular lesions in APS. Additionally, new variables are
being implemented to assess the risk of thrombosis in patients with APS. Global
APS Score (GAPSS) utilizes cardiovascular risk factors and new autoimmune
antibodies as part of the score assessment and is the most valid so far. It can
be a promising tool in the future for prediction of thrombosis. Anticoagulation
remains the cornerstone in APS; however, many new potential therapeutic agents
are developing and are currently under investigation. CONCLUSIONS: The most
recent advances in pathogenesis, risk stratification and treatment provide a
platform for high yield studies with the ultimate goal of providing the optimal
management to patients with APS.
PMID- 25851449
TI - Trajectories of relationship stress and inflammatory processes in adolescence.
AB - Researchers have identified cross-sectional links between interpersonal stress
and inflammation. Little is known, however, about how these dynamics unfold over
time, what underlying immune pathways might exist, or whether moderators such as
race could alter the strength of the connection between interpersonal stress and
inflammatory processes. We examined whether adolescent girls whose relationship
trajectories were characterized by chronic stress would exhibit a proinflammatory
phenotype marked by systemic inflammation, heightened cytokine responses to
bacterial challenges, and resistance to the anti-inflammatory properties of
cortisol. Significant Stress * Race interactions revealed that family stress
trajectories predicted glucocorticoid sensitivity and peer stress trajectories
predicted cytokine production for White but not Asian girls. Relationship stress
trajectories were not associated with systemic inflammation, however. These
findings suggest that particular subgroups of adolescent girls who face chronic
and elevated stress in their close relationships may be at risk for disruptions
to the immune system.
PMID- 25851450
TI - Reconstruction of the Traumatized Thumb.
PMID- 25851452
TI - Vertical augmentation/mastopexy: "surgeon, embrace".
PMID- 25851453
TI - Use of a urea, arginine and carnosine cream versus a standard emollient glycerol
cream for treatment of severe xerosis of the feet in patients with type 2
diabetes: a randomized, 8 month, assessor-blinded, controlled trial.
AB - BACKGROUND: No long-term data are available regarding the effects of emollients
in treating severe foot skin xerosis in patients with diabetes. STUDY AIM: We
evaluated the efficacy of 8 month urea, arginine and carnosine cream (UC) in
comparison with a glycerin-based emollient cream (SEC) in type 2 patients with
diabetes who had severe foot xerosis. SUBJECTS AND METHODS: We assessed the
effect of UC and SEC on skin hydration in a randomized, assessor-blinded study in
50 patients treated with UC (N = 25) or SEC (N = 25) for 32 weeks with a twice
daily application. Primary outcomes were a 9 point Xerosis Assessment Scale (XAS)
score and a 4 point Overall Cutaneous Score (OCS), evaluated at baseline and
after 4, 12 and 32 weeks. Skin hydration and desquamation were also objectively
evaluated by means of a bio-impedance skin analysis device (Hydr8 * ) at baseline
and at week 32. RESULTS: UC induced greater hydration than SEC (p = 0.001) with a
91% reduction at week 32 in XAS score vs. baseline. After 4 weeks, compared with
the SEC treated group, the XAS score in the UC treated group was significantly
lower. OCS was reduced by 27% from baseline to end of the study in the UC group,
and increased by 8% in the SEC group (p = 0.02; between groups). At month 8, skin
hydration and desquamation evaluated by the digital skin analysis system
statistically improved in UC treated subjects in comparison with baseline and SEC
group values. This study was not double-blind. In order to overcome this problem
we performed an assessor-blinded evaluation of the primary endpoints and used an
objective measurement tool for skin hydration and desquamation assessment.
CONCLUSION: Using a urea, arginine and carnosine cream for 8 months increases
skin hydration and improves skin dryness in type 2 diabetic patients in
comparison with a glycerol-based emollient cream, with a greater efficacy
observed as early as 4 weeks into treatment.
PMID- 25851454
TI - Consent forms for "no surgery" as ramification of landmark ruling.
PMID- 25851455
TI - Sodium MRI of multiple sclerosis.
AB - Multiple sclerosis (MS) is the most common cause of non-traumatic disability in
young adults. The mechanisms underlying neurodegeneration and disease progression
are poorly understood, in part as a result of the lack of non-invasive methods to
measure and monitor neurodegeneration in vivo. Sodium MRI is a topic of
increasing interest in MS research as it allows the metabolic characterization of
brain tissue in vivo, and integration with the structural information provided by
(1)H MRI, helping in the exploration of pathogenetic mechanisms and possibly
offering insights into disease progression and monitoring of treatment outcomes.
We present an up-to-date review of the sodium MRI application in MS organized
into four main sections: (i) biological and pathogenetic role of sodium; (ii)
brief overview of sodium imaging techniques; (iii) results of sodium MRI
application in clinical studies; and (iv) future perspectives.
PMID- 25851456
TI - Utility of the QT interval in predicting outcomes in patients presenting to the
emergency department with chest pain.
AB - OBJECTIVES: The aim of this study was to investigate whether prolongation of the
heart rate-corrected QT interval (QTc) is an independent risk factor for
predicting future acute coronary syndrome (ACS) occurrence or mortality in
patients with at least one cardiac risk factor presenting with chest pain to the
emergency department (ED). METHODS: This is a single-center, retrospective study
of patients presenting with chest pain to the ED of Einstein Medical Center,
Philadelphia, between 2011 and 2012. Proportional hazards models were used to
calculate hazard ratios (HRs) for occurrence of ACS or death within 1 year.
Kaplan-Meier curves were used to determine the time to event for QTc low (< 460
ms) versus QTc high (>= 460 ms) groups. RESULTS: A total of 595 patients met the
inclusion criteria. Older age, hypertension, diabetes mellitus, and
hyperlipidemia were more common in the QTc high group. Patients in the QTc high
group were more likely to experience subsequent ACS or death (HR 8.12, 95%
confidence interval 4.00-16.72), even after adjusting for traditional cardiac
risk factors (HR 7.68, 95% confidence interval 3.57-16.61). CONCLUSION: QTc
prolongation at ED presentation with chest pain and at least one cardiac risk
factor predicts subsequent ACS and death.
PMID- 25851458
TI - Chronic widespread pain: clinical comorbidities and psychological correlates.
AB - Recent studies have provided consistent evidence for a genetic influence on
chronic widespread pain (CWP). The aim of this study was to investigate (1) the
etiological structure underlying CWP by examining the covariation between CWP and
psychological comorbidities and psychoaffective correlates and (2) the
decomposition of the covariation into genetic and environmental components. A
total of 3266 female twins (mean age 56.6 years) were subject to multivariate
analyses. Using validated questionnaires to classify twins as having CWP, the
prevalence of CWP was 20.8%. In the multivariate analysis, the most suitable
model was the common pathway model. This model revealed 2 underlying latent
variables, one common to anxiety, emotional intelligence, and emotional
instability (f1) and the other common to depression and CWP (f2), the latter
being highly heritable (86%). Both latent variables (f1 and f2) shared an
additive genetic and a nonshared environmental factor. In addition, a second
additive genetic factor loading only on f2 was found. This study reveals the
structure of genetic and environmental influences of CWP and its psychoaffective
correlates. The results show that the clustering of CWP and depression is due to
a common, highly heritable, underlying latent trait. In addition, we found
evidence that CWP, anxiety, emotional instability, and emotional intelligence are
influenced by different underlying latent traits sharing the same genetic and
nonshared environmental factors. This is the first study to reveal the structure
and relative importance of genetic and environmental influences on complex
etiological mechanisms of CWP and its correlates.
PMID- 25851457
TI - Chronic constriction injury-induced nociception is relieved by nanomedicine
mediated decrease of rat hippocampal tumor necrosis factor.
AB - Neuropathic pain is a chronic pain syndrome that arises from nerve injury.
Current treatments only offer limited relief, clearly indicating the need for
more effective therapeutic strategies. Previously, we demonstrated that
proinflammatory tumor necrosis factor-alpha (TNF) is a key mediator of
neuropathic pain pathogenesis; TNF is elevated at sites of neuronal injury, in
the spinal cord, and supraspinally during the initial development of pain. The
inhibition of TNF action along pain pathways outside higher brain centers results
in transient decreases in pain perception. The objective of this study was to
determine whether specific blockade of TNF in the hippocampus, a site of pain
integration, could prove efficacious in reducing sciatic nerve chronic
constriction injury (CCI)-induced pain behavior. Small inhibitory RNA directed
against TNF mRNA was complexed to gold nanorods (GNR-TNF siRNA; TNF nanoplexes)
and injected into the contralateral hippocampus of rats 4 days after unilateral
CCI. Withdrawal latencies to a noxious thermal stimulus (hyperalgesia) and
withdrawal to innocuous forces (allodynia) were recorded up to 10 days and
compared with baseline values and sham-operated rats. Thermal hyperalgesia was
dramatically decreased in CCI rats receiving hippocampal TNF nanoplexes; and
mechanical allodynia was transiently relieved. TNF levels (bioactive protein, TNF
immunoreactivity) in hippocampal tissue were decreased. The observation that TNF
nanoplex injection into the hippocampus alleviated neuropathic pain-like behavior
advances our previous findings that hippocampal TNF levels modulate pain
perception. These data provide evidence that targeting TNF in the brain using
nanoparticle-protected siRNA may be an effective strategy for treatment of
neuropathic pain.
PMID- 25851459
TI - Well, I wouldn't start from here.
PMID- 25851460
TI - Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.
AB - Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the
most commonly used class of analgesics. Increasing evidence suggests that
cyclooxygenase (COX) inhibition at both peripheral and central sites can
contribute to the antihyperalgesic effects of NSAIDs, with the predominant
clinical effect being mediated centrally. In this study, we examined the cerebral
response to ibuprofen in presurgical and postsurgical states and looked at the
analgesic interaction between surgical state and treatment. We used an
established clinical pain model involving third molar extraction, and
quantitative arterial spin labelling (ASL) imaging to measure changes in
tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual
analogue scales inside the scanner to evaluate the subjective experience of pain.
This novel methodology was incorporated into a randomized double-blind placebo
controlled design, with an open method of drug administration. We found that
independent of its antinociceptive action, ibuprofen has no effect on regional
cerebral blood flow under pain-free conditions (presurgery). However, in the
postsurgical state, we observed increased activation of top-down modulatory
circuits, which was accompanied by decreases in the areas engaged because of
ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic
response in the human brain, with the subjective effects of pain relief reflected
in two distinct brain networks. The observed activation of descending modulatory
circuits warrants further investigation, as this may provide new insights into
the inhibitory mechanisms of analgesia that might be exploited to improve safety
and efficacy in pain management.
PMID- 25851461
TI - Destructive Spondyloarthropathy in Patients on Long-Term Peritoneal Dialysis or
Hemodialysis.
AB - Destructive spondyloarthropathy (DSA) is the most serious spinal complication of
dialysis-related amyloidosis in patients on long-term hemodialysis (HD), but we
could not find any information about DSA in patients on peritoneal dialysis (PD)
for over 10 years. We retrospectively evaluated factors contributing to DSA in HD
and PD patients. Sixty-seven patients on dialysis for 10 to 19 years were
compared between a PD group (n = 23) or a HD group (n = 44). In the PD group,
nine patients (39%) developed DSA. The mean age of DSA patients was significantly
higher than that of non-DSA patients (66.2 +/- 10.0 vs. 51.0 +/- 12.8 years, P =
0.03). The frequency of cervical spine DSA did not show any difference between
the PD and HD groups, but the frequency of lumbar spine DSA showed a significant
difference (22% vs. 5%, P = 0.04). The serum beta-2 microglobulin (B2MG) level
was significantly higher in PD patients than in HD patients (38.4 mg/L vs. 27.4
mg/L, P = 0.0025). Mechanical stress such as elevation of the intra-abdominal
pressure due to infusion of PD fluid (1500 mL to 2000 mL) for over 10 years might
contribute to lumbar DSA in patients on long-term PD.
PMID- 25851462
TI - Health care managers' views on and approaches to implementing models for
improving care processes.
AB - AIM: To develop a deeper understanding of health-care managers' views on and
approaches to the implementation of models for improving care processes.
BACKGROUND: In health care, there are difficulties in implementing models for
improving care processes that have been decided on by upper management.
Leadership approaches to this implementation can affect the outcome. METHOD: In
depth interviews with first- and second-line managers in Swedish hospitals were
conducted and analysed using grounded theory. RESULTS: 'Coaching for
participation' emerged as a central theme for managers in handling top-down
initiated process development. The vertical approach in this coaching addresses
how managers attempt to sustain unit integrity through adapting and translating
orders from top management. The horizontal approach in the coaching refers to
managers' strategies for motivating and engaging their employees in
implementation work. CONCLUSION AND IMPLICATIONS FOR NURSING MANAGEMENT:
Implementation models for improving care processes require a coaching leadership
built on close manager-employee interaction, mindfulness regarding the pace of
change at the unit level, managers with the competence to share responsibility
with their teams and engaged employees with the competence to share
responsibility for improving the care processes, and organisational structures
that support process-oriented work. Implications for nursing management are the
importance of giving nurse managers knowledge of change management.
PMID- 25851463
TI - Aristotle, Hume and the goals of medicine.
AB - Whilst medicine is now an immense global industry clinicians often appear unclear
as to its goals. This paper uses two philosophical steps to clarify our
conceptualization of health and thus our goals for healthcare. Firstly,
clinicians need to understand the significance of Hume's fact / value distinction
in medicine, for medicine relies on both facts and values. Secondly clinicians
need a better specified definition of 'health' to use as a goal for healthcare.
Aristotle's model of human flourishing is used as the starting point for a new
conceptualization of health.
PMID- 25851464
TI - Polydentate chalcogen reagents for the facile preparation of Pd2 and Pd4
complexes.
AB - The silylated organochalcogen reagents 1,2-(Me3SiSCH2)2C6H4, and 1,2
(Me3SiSeCH2)2C6H4, were prepared from the corresponding organobromides and
lithium trimethylsilanechalcogenolate Li[ESiMe3] (E = S, Se). They have been
characterized by multinuclear NMR spectroscopy ((1)H, (13)C, (77)Se) and
electrospray ionization mass spectrometry. and react under mild conditions with
(1,3-bis(diphenylphosphino)propane)palladium(ii) chloride, [PdCl2(dppp)], to
provide the dinuclear organochalcogenolate-bridged complexes [(dppp)2Pd2-MU
kappa(2)S-{1,2-(SCH2)2C6H4}]X2, []X2 and [(dppp)2Pd2-MU-kappa(2)Se-{1,2
(SeCH2)2C6H4}]X2, []X2 (X = Cl, Br) in good yield, respectively. Furthermore, the
tetranuclear palladium complex [(dppp)4Pd4-MU-kappa(4)S-{1,2,4,5-(SCH2)4C6H2}]X4,
[]X4 (X = Cl, Br) can be synthesized from the reaction of the
tetrathiotetrasilane 1,2,4,5-(Me3SiSCH2)4C6H2, and [PdCl2(dppp)]. The structures
of []X2, []X2 and []X4 were determined by single crystal X-ray diffraction
methods. A variety of NMR experiments including two-dimensional homonuclear and
heteronuclear correlated spectra were used to probe the solution behaviour of the
dinuclear complexes in more detail. These complexes were further characterized by
electrospray ionization (ESI) mass spectrometry, and for []X2 and []X2, UV-Vis
absorption spectroscopy.
PMID- 25851465
TI - HLA-DQ allele-restricted activation of nitroso sulfamethoxazole-specific CD4
positive T lymphocytes from patients with cystic fibrosis.
AB - BACKGROUND: For certain HLA allele-associated drug hypersensitivity reactions,
the parent drug has been shown to associate directly with the risk allele. In
other forms of hypersensitivity, HLA risk alleles have not been identified and T
cells are activated in an allele unrestricted manner. Chemically reactive drug
metabolites bind to multiple proteins; thus, it is assumed that the derived
peptide antigens interact with a number of HLA molecules to activate T cells;
however, HLA restriction of the drug metabolite-specific T-cell response has not
been studied. OBJECTIVE: To utilize T cells from sulfamethoxazole (SMX)
hypersensitive patients with cystic fibrosis to examine the HLA molecules that
interact with nitroso SMX (SMX-NO)-derived antigens. METHODS: T-cell clones were
generated from 4 hypersensitive patients. Drug-specific proliferative responses
and cytokine secretion were measured. Anti-human class I and class II antibodies
were used to analyse HLA restriction. Antigen-presenting cells expressing
different HLA molecules were used to determine the alleles involved in the
presentation of SMX-NO-derived antigens to T cells. RESULTS: A total of 976
clones were tested for SMX-NO reactivity. Thirty-nine CD4+ clones were activated
with SMX-NO and found to proliferate and secrete cytokines. The SMX-NO-specific
response was blocked with an antibody against HLA-DQ. SMX-NO-specific responses
were detected with antigen-presenting cells expressing HLA-DQB1*05:01 (patient 1)
and HLA-DQB1*02:01 (patient 2), but not other HLA-DQB1 alleles. CONCLUSION AND
CLINICAL RELEVANCE: HLA-DQ plays an important role in the activation of SMX-NO
specific CD4+ T cells. Detection of HLA-DQ allele-restricted responses suggests
that T cells are activated by a limited repertoire of SMX-NO-modified peptides.
PMID- 25851467
TI - Usefulness of a tailored metallic Y stent for the treatment of complex post-lung
transplant bronchial stenosis.
PMID- 25851466
TI - Combination of liver biopsy with MELD-XI scores for post-transplant outcome
prediction in patients with advanced heart failure and suspected liver
dysfunction.
AB - BACKGROUND: Functional and structural liver abnormalities may be found in
patients with advanced heart failure (HF). The Model of End-Stage Liver Disease
Excluding INR (MELD-XI) score allows functional risk stratification of HF
patients on and off anti-coagulation awaiting heart transplantation (HTx), but
these scores may improve or worsen depending on bridging therapies and during
time on the waiting list. Liver biopsy is sometimes performed to assess for
severity of fibrosis. Uncertainty remains whether biopsy in addition to MELD-XI
improves prediction of adverse outcomes in patients evaluated for HTx. METHODS:
Sixty-eight patients suspected of advanced liver disease underwent liver biopsy
as part of their HTx evaluation. A liver risk score (fibrosis-on-biopsy + 1) *
MELD-XI was generated for each patient. RESULTS: Fifty-two patients were listed,
of whom 14 had mechanical circulatory support (MCS). Thirty-six patients
underwent transplantation and 27 patients survived >=1 year post-HTx (74%, as
compared with 88% average 1-year survival in HTx patients without suspected liver
disease; p < 0.01). Survivors had a lower liver risk score at evaluation for HTx
(31.0 +/- 20.4 vs 65.2 +/- 28.6, p < 0.01). A cut-point of 45 for liver risk
score was identified by receiver-operating-characteristic (ROC) analysis. In the
analysis using Cox proportional hazards models, a liver risk score >=45 at
evaluation for HTx was associated with greater risk of death at 1 year post-HTx
compared with a score of <45 in both univariable (HR 3.94, 95% CI 1.77-8.79, p <
0.001) and multivariable (HR 4.35, 95% CI 1.77-8.79, p < 0.001) analyses.
Patients who died <1 year post-HTx had an increased frequency of acute graft
dysfunction (44.4% vs 3.7%, p = 0.009), longer ventilation times (55.6% vs 11.1%,
p = 0.013) and severe bleeding events (44.4% vs 11.1%, p = 0.049). The liver risk
score at evaluation for HTx also predicted 1-year mortality after HTx listing (p
< 0.001). CONCLUSIONS: Patients with HF and advanced liver dysfunction are high
risk HTx candidates. Liver biopsy in addition to MELD-XI improves risk
stratification of patients with advanced HF and suspected irreversible liver
dysfunction.
PMID- 25851468
TI - Effect of Anti-Sticking Nanostructured Surface Coating on Minimally Invasive
Electrosurgical Device in Brain.
AB - The purpose of the present study was to examine the extent of thermal injury in
the brain after the use of a minimally invasive electrosurgical device with a
nanostructured copper-doped diamond-like carbon (DLC-Cu) surface coating. To
effectively utilize an electrosurgical device in clinical surgery, it is
important to decrease the thermal injury to the adjacent tissues. The surface
characteristics and morphology of DLC-Cu thin film was evaluated using a contact
angle goniometer, scanning electron microscopy, and atomic force microscopy.
Three-dimensional biomedical brain models were reconstructed using magnetic
resonance images to simulate the electrosurgical procedure. Results indicated
that the temperature was reduced significantly when a minimally invasive
electrosurgical device with a DLC-Cu thin film coating (DLC-Cu-SS) was used.
Temperatures decreased with the use of devices with increasing film thickness.
Thermographic data revealed that surgical temperatures in an animal model were
significantly lower with the DLC-Cu-SS electrosurgical device compared to an
untreated device. Furthermore, the DLC-Cu-SS device created a relatively small
region of injury and lateral thermal range. As described above, the biomedical
nanostructured film reduced excessive thermal injury with the use of a minimally
invasive electrosurgical device in the brain.
PMID- 25851469
TI - Assessment of a Four-View Mammographic Image Feature Based Fusion Model to
Predict Near-Term Breast Cancer Risk.
AB - The purpose of this study was to develop and assess a new quantitative four-view
mammographic image feature based fusion model to predict the near-term breast
cancer risk of the individual women after a negative screening mammography
examination of interest. The dataset included fully-anonymized mammograms
acquired on 870 women with two sequential full-field digital mammography
examinations. For each woman, the first "prior" examination in the series was
interpreted as negative (not recalled) during the original image reading. In the
second "current" examination, 430 women were diagnosed with pathology verified
cancers and 440 remained negative ("cancer-free"). For each of four bilateral
craniocaudal and mediolateral oblique view images of left and right breasts, we
computed and analyzed eight groups of global mammographic texture and tissue
density image features. A risk prediction model based on three artificial neural
networks was developed to fuse image features computed from two bilateral views
of four images. The risk model performance was tested using a ten-fold cross
validation method and a number of performance evaluation indices including the
area under the receiver operating characteristic curve (AUC) and odds ratio (OR).
The highest AUC = 0.725 +/- 0.026 was obtained when the model was trained by gray
level run length statistics texture features computed on dense breast regions,
which was significantly higher than the AUC values achieved using the model
trained by only two bilateral one-view images (p < 0.02). The adjustable OR
values monotonically increased from 1.0 to 11.8 as model-generated risk score
increased. The regression analysis of OR values also showed a significant
increase trend in slope (p < 0.01). As a result, this preliminary study
demonstrated that a new four-view mammographic image feature based risk model
could provide useful and supplementary image information to help predict the near
term breast cancer risk.
PMID- 25851471
TI - B-type natriuretic peptide response and reverse left ventricular remodeling after
surgical correction of functional mitral regurgitation in patients with advanced
cardiomyopathy.
AB - BACKGROUND: Restrictive mitral annuloplasty (RMA) can reverse left ventricular
(LV) remodeling and reduce plasma B-type natriuretic peptide (BNP), a surrogate
biomarker of heart failure. However, the relationship between reverse LV
remodeling and plasma BNP changes after RMA is poorly defined. We explored the
main hemodynamic factors contributing to change in plasma BNP after RMA in
patients with functional mitral regurgitation (MR). METHODS: Twenty-four patients
with moderate to severe functional MR secondary to LV systolic dysfunction
[ejection fraction (EF) <40%] underwent 64-row multidetector computed tomography
(MDCT) before and 1.4 months after RMA. LV end-diastolic volume index (EDVI), end
systolic volume index (ESVI), LVEF, and regional and global end-systolic wall
stress (ESS) were calculated from 3-dimensional MDCT images, with blood samples
for plasma BNP measurement collected the same day. RESULTS: After RMA, LV volumes
and global ESS were decreased, while LVEF improved (all p<0.01). There were
significant correlations between changes in LVEDVI and LVESVI (r=0.90, p<0.0001),
LVESVI and global ESS (r=0.54, p=0.006), and global ESS and LVEF (r=-0.60,
p=0.002). The median value for the plasma BNP also decreased from 597 pg/ml
[interquartile range (IQR), 360-934 pg/ml] to 207 pg/ml (IQR, 124-271 pg/ml), in
association with changes in LVEDVI (r=0.47, p=0.019), LVESVI (r=0.56, p=0.004),
LVEF (r=-0.60, p=0.002), and global ESS (r=0.74, p<0.0001). Multivariate
regression analysis showed that global ESS change was the strongest contributor
to change in natural-log-transformed plasma BNP (standardized partial regression
coefficient=0.59, p=0.004), indicating a strong association between decrease in
LV afterload and reduction in plasma BNP level after RMA. CONCLUSIONS: There may
be a significant association between LV reverse remodeling and plasma BNP change
after RMA. Furthermore, LV end-systolic myocardial stress may be the key
mechanical stimulus influencing plasma BNP after surgical correction for
functional MR. Whether these favorable BNP responses and reverse remodeling can
predict improved survival requires further study.
PMID- 25851473
TI - Right ventricular outflow muscle in tetralogy of Fallot: Histologic and
immunohistochemical monoclonal antibody analysis.
AB - To evaluate progressive muscular right ventricular outflow tract (RVOT)
obstruction in tetralogy of Fallot (TOF), we hypothesized that this tissue would
demonstrate more prominent selected immunohistochemical markers of myogenous cell
differentiation, growth factor/receptor, and extracellular matrix. Sections of
formalin-fixed, paraffin-embedded myectomy tissue obtained from RVOT at the time
of surgical correction of TOF (n = 32; ages = 3 months through 13 years) were
compared with age-matched tissue from the RVOT of normal control hearts (n = 12)
obtained at autopsy after non-cardiac death. Examining by light microscopy slides
stained with a combination of hematoxylin and eosin and elastic trichrome
revealed cardiomyocyte (CM) hypertrophy, extensive myofiber disarray,
trabeculation, multinucleation (more than two nuclei per myocyte), fibrosis, and
thick-walled coronary arteries within the myocardium of TOF tissue. The
endocardium from TOF specimens was thickened and hypercellular with prominent
fibrosis and elastosis. Mitosis was not observed. At the interface between the
endocardium and myocardium, the TOF specimens demonstrated myocyte dispolarity
(orientation of CMs perpendicular to the endocardial surface), vascularization,
and fibrosis. Immunohistochemical studies were performed using monoclonal
antibodies to vimentin, desmin, muscle-specific actin (MSA), epidermal growth
factor (EGF), epidermal growth factor receptor (EGFR), and laminin. Compared to
the tissue from controls, TOF tissue showed a pattern of upregulated expression
of epitopes within the endocardium and adjacent subendocardial myocardium.
Decoration for MSA, vimentin, desmin, and EGFR highlighted the zonal nature of
this tissue hyperactivity. Laminin prominently outlined endocardial cells,
subendocardial CMs, and interface vessels in TOF tissue compared to the remainder
of the myocardium and tissue from controls. Overall, changes in TOF were age
related, with older patients showing less zonal myocardial reactivity. These
findings provide evidence for an ongoing, complex remodeling of the RVOT muscle
in TOF.
PMID- 25851472
TI - Patients with both CYP2C19 loss-of-function allele and peripheral endothelial
dysfunction are significantly correlated with adverse cardiovascular events
following coronary stent implantation.
AB - BACKGROUND: There is some controversy regarding the effect of CYP2C19
polymorphism on clinical outcome in patients receiving dual antiplatelet therapy
(DAPT). Peripheral endothelial dysfunction has recently been reported to predict
adverse cardiovascular events. We hypothesized that CYP2C19 loss-of-function
(LOF) allele carriers with peripheral endothelial dysfunction had worse
prognosis. The aim of this study was to evaluate an additive effect of peripheral
endothelial dysfunction on clinical outcome following percutaneous coronary
intervention (PCI) in patients with a CYP2C19 variant. METHODS: We enrolled 434
patients on DAPT following PCI. CYP2C19 genotype was examined, and we divided
patients into two groups: carriers, who had at least one CYP2C19 LOF allele, and
non-carriers. Peripheral endothelial dysfunction was examined using reactive
hyperemia-peripheral arterial tonometry index (RHI), and we divided patients into
low and high RHI. Thus, subjects were divided into four groups, and clinical
events were followed up. RESULTS: A total of 55 patients had a cardiovascular
event. Kaplan-Meier analysis demonstrated a significantly higher probability of
cardiovascular events in carriers with low RHI (log-rank test: p=0.007).
Multivariate Cox proportional hazards analysis identified both CYP2C19 LOF allele
possession (hazard ratio (HR): 1.94; 95% confidence interval (CI): 1.1-3.69;
p=0.045) and low RHI (HR: 2.15; 95% CI: 1.22-3.78; p=0.008) as independent and
significant predictors of future cardiovascular events. CONCLUSIONS: CYP2C19 LOF
allele carriers with peripheral endothelial dysfunction were significantly
correlated with cardiovascular events. The additional evaluation of peripheral
endothelial function along with CYP2C19 polymorphism might improve risk
stratification after coronary stent implantation.
PMID- 25851474
TI - Tuberculous aortitis with coronary ostial and left ventricular outflow
obstruction: Unusual cause of sudden unexpected death.
AB - Tuberculous aortitis is a distinct, but uncommon, cause of thoracic and abdominal
aortic aneurysms. We report an unusual case of tuberculous aortitis in a 12-year
old girl that resulted in her sudden death. The patient suffered from undiagnosed
primary pulmonary tuberculosis affecting the apical region of her right lower
lobe, with regional hilar lymphadenopathy. The granulomatous inflammatory process
spread from the hilar lymph nodes to the aortic root, leading to tuberculous
aortitis and the formation of an intraluminal tuberculoma just superior to the
aortic valve. The tuberculoma also involved the ostia and proximal portions of
both coronary arteries, resulting in obstruction of the coronary arteries in
addition to the left ventricular outflow tract. The consequent myocardial fiber
hypertrophy and interstitial fibrosis predisposed the patient to the development
of fatal arrhythmias that most probably accounted for her sudden death.
PMID- 25851475
TI - Endomyocardial biopsy findings in patients with ventricular arrhythmias of
unknown origin.
AB - To evaluate possible occult myocardial disease in patients with ventricular
arrhythmias of unknown origin, over 11 years right ventricular endomyocardial
biopsies (EMB) were performed on 80 consecutive such patients (29 Females, 51
Males; median age 42 years). Seventy-one (89%) had ventricular tachycardia or
fibrillation, 7 (9%) had complex ventricular arrhythmias, and 2 (3%) had
premature ventricular beats. None showed clinical evidence of congestive heart
failure or significant coronary artery or valvular disease. Endomyocardial
biopsies revealed pathologic changes in 70 out of 80 patients (88%). Of the 70
affected, 39 (56%) had nonspecific changes consistent with cardiomyopathy (e.g.,
myofiber hypertrophy, interstitial and perivascular fibrosis, and vascular
sclerosis); 6 (9%) had active myocarditis (Myo); 7 (10%) had borderline Myo; 7
(10%) had small vessel disease; 6 (9%) had changes consistent with arrhythmogenic
cardiomyopathy; 2 (3%) had amyloidosis; 2 (3%) had microfibrillar cardiomyopathy,
and one (1.0%) showed intravascular organizing thrombus. Thus, EMB reveals a
variety of abnormalities in the majority of patients presenting with ventricular
arrhythmias without clinical evidence of structural heart disease.
PMID- 25851476
TI - Morphology of the atrioventricular valve in asplenia syndrome: A peculiar type of
atrioventricular canal defect.
AB - The high risk of atrioventricular (AV) valve regurgitation is a major point of
concern in the natural history of patients with atrioventricular canal defect
(AVCD) and asplenia syndrome (AS). The morphology of the common AV valve in
patients with AVCD and AS was therefore studied and compared with the anatomy of
patients with AVCD but with atrial situs solitus. We compared the anatomic
features of hearts with common AV valve (ventricular loop; AV valve alignment on
ventricles; number of leaflets; number and morphology of papillary muscles and
relationship of the bridging leaflets with the ventricular septum) in the hearts
of 33 patients with AVCD and asplenia syndrome (Group 1) with those of 44
patients with common AV valve, complete AVCD, and atrial situs solitus (Group 2).
Hearts featuring asplenia syndrome showed a significantly higher occurrence of
anomalies of the ventricular loop (p < .0001), right ventricular dominance (p <
.01), and a reduced number of valvular leaflets and papillary muscles (p <
.0005). On the contrary, hearts with situs solitus of the atria showed a
significantly higher frequency of balanced ventricles (p < .0001) and a common AV
valve with five leaflets and five papillary muscles (p < .000001). These data
suggest that AVCDs in association with asplenia syndrome present morphologic
peculiarities that may be considered as the substrate for the abnormal
regurgitation. Recognizing the presence of these features could be of great value
for the planning of a specific surgical treatment. These anatomic differences
support the hypothesis of a genetic heterogeneity of AVCDs.
PMID- 25851477
TI - Heart-lung transplantation: Cardiac clinicopathological correlations.
AB - Reports on heart-lung transplantation emphasize the pathology of the transplanted
lungs. This study is a clinicopathological assessment of cardiac pathology in the
hearts transplanted as part of the combined heart-lung block. Seventy-five
consecutive heart-lung transplants (H-LTx) performed between 1981 and 1989 were
studied. Endomyocardial biopsy, autopsy and clinical data were analyzed for
information on cardiac rejection, graft coronary disease, transplant survival and
the presence of obliterative bronchiolitis and compared with controls. The
controls consisted of 391 heart transplants (HTx) performed in 361 recipients
over the same time period. Sixty-three adults and nine children received H-LTx
(48.6% male; 51.4% female). In this study, H-LTx were performed primarily for
Eisenmenger's complex (33 72 ) and primary pulmonary hypertension (28 72 ). At 1
year H-LTx survival was 63.88%, versus 81.54% in HTx alone and 63.63% in lung
transplant recipients without heart grafts. The results showed that H-LTx
patients have less cardiac rejection compared to patients who undergo HTx alone
(p < .005). Only 40% of H-LTx recipients developed acute cardiac rejection in the
initial 3 months posttransplantation (post-Tx), compared with 80% of HTx
controls. Only 4% of H-LTx recipients developed cardiac rejection after the
initial 6 months. No cardiac rejection was observed in the initial 5 years post
Tx in 49.9% of H-LTx. Graft coronary disease was seen in 7.73% of H-LTx within
the first 5 years post-Tx compared with 25.87% in HTx recipients alone (p <
.005). Obliterative bronchiolitis (OB) was present in 71.43% of H-LTx with graft
coronary disease, compared to OB in only 41.38% of H-LTx without graft coronary
disease (p < .05). In conclusion, H-LTx recipients have less acute cardiac
rejection episodes than HTx recipients alone (p < .005). Most cardiac rejection
in H-LTx occurs within the initial 6 months. In addition, H-LTx recipients
develop less graft coronary disease than HTx recipients (p < .005). Obliterative
bronchiolitis and graft coronary disease may be the result of the same
immunological process, as 71.43% of H-LTx with graft coronary disease also had
OB. Survival for H-LTx patients is more similar to that of lung transplant (LTx)
patients alone than that of heart transplants alone, suggesting that it is the
pulmonary pathology portion, rather than the cardiac pathology portion, in
combined H-LTx transplants that contributes more to H-LTx survival.
PMID- 25851478
TI - Myasthenia gravis-associated systemic vasculitis and myocarditis with involvement
of the cardiac conducting tissue.
AB - We describe unexpected autopsy findings in an elderly woman with myasthenia
gravis (MG) who had myocarditis of the working and conducting myocardium and
coronary and renal vasculitis. Myasthenia gravis, characterized by autoantibodies
to the acetylcholine receptor in the postsynaptic cell membrane, may be
associated with other autoimmune disorders. An additional manifestation of
autoimmunity is the presence of heart muscle antibodies, which may be the basis
for myocarditis, which has been reported in up to 60% of MG patients at autopsy.
Although myocarditis of the working myocardium is rather common, conduction
system myocarditis and systemic vasculitis have not been previously reported in
MG.
PMID- 25851479
TI - Severe postcardiac-transplant rejection associated with recurrence of giant cell
myocarditis.
AB - Giant cell myocarditis is a disease of unknown etiology with several
controversial aspects: clinical course, therapeutic management, recurring risk
after heart transplantation, and histopathological factors. We report a case of
giant cell myocarditis that recurred after orthotopic heart transplantation and
an uneventful postoperative period. The myocardial inflammatory process in this
patient showed various evolutive phases: an acute onset of diffuse giant cell
myocarditis, an evolution into a granulomatous form of inflammation within the
explanted heart, and a recurrence with multiple giant cell inflammatory
infiltrates in the transplanted heart. Moreover, the patient presented a severe
clinical course after surgery with precocious and continuous acute rejections
despite the repeated immunosuppressive treatments. In this article we discuss the
morphological aspects of the disease and the postoperative course of this case in
relation to the possible immune dysregulation of patients affected by myocarditis
before heart transplantation.
PMID- 25851480
TI - Cardiac pentastomiasis and tuberculosis: The worm-eaten heart.
AB - We report an autopsy case of disseminated tuberculosis and a coexisting,
extremely rare parasitic zoonosis: pentastomiasis. The parasite was incidentally
found in the pericardial sac and epicardium, associated with tuberculous
pericarditis, in a 43-year-old woman from Georgia with presumptive Acquired
Immunodeficiency Syndrome (AIDS). The cuticle was the only remaining intact
structure of the parasite. The internal organs had undergone autolysis, but
recognizable features were apparent. Gross and microscopic findings were highly
suggestive of pentastomid species. The ultrastructure of the cuticle was
consistent with a pentastomid arthropod. This is one of the few cases of visceral
pentastomiasis reported in North America, and the first known example of heart
involvement. The association of the parasitic infection and tuberculous
pericarditis makes the case even more unusual.
PMID- 25851481
TI - Displacement of a commissure of the "Intact" porcine bioprosthesis resulting in
valvular insufficiency.
PMID- 25851482
TI - Definition of the arterial intima.
PMID- 25851483
TI - Historical and contemporary cultural ecosystem service values in the rapidly
urbanizing city state of Singapore.
AB - Cultural ecosystem services are a function of people and place, so may change as
a location transitions from rural to urban. Singapore has undergone rapid
urbanization after its independence in 1965, with a concomitant decline in
natural habitat extent and accessibility. Using coastal mangrove forests as a
case study habitat, changing cultural values were explored with a novel array of
techniques, including qualitative archival analysis (photographs, oral
histories), current sources (publically uploaded social media photographs), and
surveys of (a) the general public and (b) visitors to publically accessible
mangroves. Cultural value changed through time, with a significant transition
from intrinsic, intrapersonal values (spiritual, cultural heritage) to
instrumental, interpersonal values (recreation, education). Additionally,
cultural value varied between different mangroves depending on their public
accessibility, and the evolving degree of human interaction with the ecosystem as
urban development occured. Cultural values change as development transitions,
though mangroves still play an important cultural role in a heavily urbanized
environment.
PMID- 25851484
TI - Decline of traditional rice farming constrains the recovery of the endangered
Asian crested ibis (Nipponia nippon).
AB - Traditional agriculture benefits a rich diversity of plants and animals. The
winter-flooded rice fields in the Qinling Mountains, China, are the last refuge
for the endangered Asian crested ibis (Nipponia nippon), and intensive efforts
have been made to protect this anthropogenic habitat. Analyses of multi-temporal
satellite data indicate that winter-flooded rice fields have been continuously
reduced across the current range of crested ibis during the past two decades. The
rate of loss of these fields in the core-protected areas has unexpectedly
increased to a higher level than that in non-protected areas in the past decade.
The best fit (R (2) = 0.87) numerical response model of the crested ibis
population shows that a reduction of winter-flooded rice fields decreases
population growth and predicts that the population growth will be constrained by
the decline of traditional winter-flooded rice fields in the coming decades. Our
findings suggest that the decline of traditional rice farming is likely to
continue to pose a threat to the long-term survival and recovery of the crested
ibis population in China.
PMID- 25851485
TI - Nalmefene for Reducing Alcohol Consumption in People with Alcohol Dependence: An
Evidence Review Group Perspective of a NICE Single Technology Appraisal.
AB - As part of its single technology appraisal process, the National Institute for
Health and Care Excellence (NICE) invited the company (Lundbeck) marketing
nalmefene (Selincro) to submit evidence of its clinical and cost effectiveness
for reducing alcohol consumption in people with alcohol dependence. The School of
Health and Related Research Technology Appraisal Group at the University of
Sheffield was commissioned to act as the independent Evidence Review Group (ERG)
and to produce a critical review of the company's submission to NICE. The
clinical evidence was derived from three phase III, company-sponsored,
randomised, double-blind, placebo-controlled trials in adults with a diagnosis of
alcohol dependence comparing nalmefene, taken on an as-needed basis, in
conjunction with psychosocial support with placebo in conjunction with
psychosocial support. Psychosocial support was provided in the form of BRENDA, an
intervention of lower intensity than that recommended in NICE Clinical Guideline
115 (NICE CG115). Post-hoc subgroup analyses were conducted in people who were
drinking at high or very high risk levels at baseline and maintained this level
of drinking during the screening phase prior to randomisation. This subgroup
forms the licensed population. There were a number of limitations and
uncertainties in the clinical evidence base which warrant caution in its
interpretation. In particular, the post-hoc subgroup analyses and high dropout
rates in the three nalmefene studies meant that the inference of treatment
effects might be confounded. The company's economic evaluation showed that use of
nalmefene in conjunction with psychosocial support in the form of BRENDA
dominated the use of BRENDA in conjunction with placebo, providing more quality
adjusted life-years (QALYs) at a reduced cost. However, this evaluation did not
meet the final scope issued by NICE, which specified that the comparator should
be psychological intervention as defined in NICE CG115. The ERG produced
alternative cost per QALY values for the comparison undertaken by the company and
suggested three further comparisons deemed relevant: (1) nalmefene with
psychological intervention as defined in NICE CG115; (2) delayed use of nalmefene
in those who did not respond to psychological intervention as recommended in NICE
CG115 alone; and (3) use of naltrexone outside of its marketing authorisation.
The ERG thought it probable that using nalmefene in only those people who do not
respond to psychological intervention alone was likely to be more cost effective
compared with its immediate use in the entire licensed population. The Appraisal
Committee accepted the comparison with psychosocial support in the form of BRENDA
and believed that the most plausible cost per QALY was likely to be below L5100.
Therefore, the Appraisal Committee concluded that nalmefene in conjunction with
psychosocial support was a cost effective use of NHS resources compared with
psychosocial support alone for treating people with alcohol dependence drinking
at a high risk level, without physical withdrawal symptoms and not requiring
immediate assisted withdrawal from alcohol.
PMID- 25851486
TI - Characterizing Heterogeneity Bias in Cohort-Based Models.
AB - PURPOSE: Previous research using numerical methods suggested that use of a cohort
based model instead of an individual-based model can result in significant
heterogeneity bias. However, the direction of the bias is not known a priori. We
characterized mathematically the conditions that lead to upward or downward bias.
METHOD: We used a standard three-state disease progression model to evaluate the
cost effectiveness of a hypothetical intervention. We solved the model
analytically and derived expressions for life expectancy, discounted quality
adjusted life years (QALYs), discounted lifetime costs and incremental net
monetary benefits (INMB). An outcome was calculated using the mean of the input
under the cohort-based approach and the whole input distribution for all persons
under the individual-based approach. We investigated the impact of heterogeneity
on outcomes by varying one parameter at a time while keeping all others constant.
We evaluated the curvature of outcome functions and used Jensen's inequality to
determine the direction of the bias. RESULTS: Both life expectancy and QALYs were
underestimated by the cohort-based approach. If there was heterogeneity only in
disease progression, total costs were overestimated, whereas QALYs gained,
incremental costs and INMB were under- or overestimated, depending on the
progression rate. INMB was underestimated when only efficacy was heterogeneous.
Both approaches yielded the same outcome when the heterogeneity was only in cost
or utilities. CONCLUSION: A cohort-based approach that does not adjust for
heterogeneity underestimates life expectancy and may underestimate or
overestimate other outcomes. Characterizing the bias is useful for comparative
assessment of models and informing decision making.
PMID- 25851488
TI - Endothelial cell icam-1 staining in human carotid arteries.
AB - In this study human carotid artery specimens from 18 patients were examined by an
en face technique to demonstrate the endothelial cell staining of intercellular
adhesion molecule-1 (ICAM-1). Endothelial cells about the carotid bifurcation and
within the post-stenotic region of the internal carotid artery were predominately
polyhedral in shape with heterogenous but often intense ICAM-1 staining.
Endothelium lining the partially stenosed lumen of the intern carotid orifice
were elongated with ICAM-1 staining often polarized at the proximal end of the
cell. There were two dominant patterns of ICAM-1 staining associated with
polyhedral endothelial cells, cell border, and cell surface/nuclear profile
staining. Polyhedral cells at the proximal end of the internal carotid artery
stenosis appeared to have both patterns while those at the distal end were most
often observed with only the cell surface expression pattern. Adherent leukocytes
were mostly observed in association with polyhedral endothelial cells especially
in the post-stenotic internal carotid and were uncommon within stenoses. These
results indicate heterogeneity not only of endothelial cell morphology but also
in the intensity and pattern of staining of ICAM-1 about atherosclerotic lesions.
This may be indicative of different functional properties for ICAM-1 depending on
anatomical localization and consequent hemodynamic stresses.
PMID- 25851487
TI - RECQ5-dependent SUMOylation of DNA topoisomerase I prevents transcription
associated genome instability.
AB - DNA topoisomerase I (TOP1) has an important role in maintaining DNA topology by
relaxing supercoiled DNA. Here we show that the K391 and K436 residues of TOP1
are SUMOylated by the PIAS1-SRSF1 E3 ligase complex in the chromatin fraction
containing active RNA polymerase II (RNAPIIo). This modification is necessary for
the binding of TOP1 to RNAPIIo and for the recruitment of RNA splicing factors to
the actively transcribed chromatin, thereby reducing the formation of R-loops
that lead to genome instability. RECQ5 helicase promotes TOP1 SUMOylation by
facilitating the interaction between PIAS1, SRSF1 and TOP1. Unexpectedly, the
topoisomerase activity is compromised by K391/K436 SUMOylation, and this provides
the first in vivo evidence that TOP1 activity is negatively regulated at
transcriptionally active chromatin to prevent TOP1-induced DNA damage. Therefore,
our data provide mechanistic insight into how TOP1 SUMOylation contributes to
genome maintenance during transcription.
PMID- 25851489
TI - Peculiarities of prevalence and morphology of congenital heart disease detected
in utero.
AB - Intrauterine echocardiography is changing our knowledge of congenital heart
disease; cardiac defects diagnosed in utero have distinctive features of both
prevalence and morphology when compared with those observed just after birth. We
reviewed a series of 171 fetal heart conditions: 148 were diagnosed at
intrauterine echocardiography, the diagnosis being verified at autopsy in 41, and
23 were observed at the postmortem only. Peculiarities of prevalence consisted in
an excess of various defects, such as hypoplastic left heart syndrome, atrial
isomerism, pulmonary atresia, and atrioventricular and atrial septal defects, and
in a reduced number of completely different conditions, such as transposition of
great arteries and aortic coarctation. Differences in prevalence have been
attributed to difficulties in diagnosing some particular anomalies in utero, to
the selection of pregnancies undergoing screening, and to the special
intrauterine evidence of some heart defects. Peculiarities in morphology result
from the coexistence with extracardiac malformations, from the changes in shape
conditioned by fetal hemodynamics, and from the intrauterine evolution of the
morphology of some malformations. We concluded that the knowledge of these
characteristic traits was helpful to cardiac pathologists, pediatric
cardiologists, and obstetricians, and allowed the re-evaluation of the role of
hemodynamic factors in remodeling the malformed cardiovascular appara-tus.
PMID- 25851490
TI - Severe congenital stenosis of the left coronary artery ostium and its possible
pathogenesis according to current knowledge on coronary artery development.
AB - We report a 72-year-old woman with severe congenital stenosis of the left
coronary artery orifice and clinically significant atherosclerotic changes in
both the right and left coronary arteries. The stenotic ostium was located at the
point at which the left and posterior aortic valve leaflets joined to form the
left commissure, just at the distal vertex of the left interleaflet triangle,
between the left and posterior aortic sinuses. The right coronary artery was more
developed in size than usual, whereas the left coronary artery consisted of a
short left main coronary trunk that bifurcated into left anterior descending and
left circumflex arteries. The left coronary artery system was filled retrogradely
through two vessels proceeding from the right coronary artery, namely, the conal
artery and a well-developed branch that ran across the interventricular septum.
This abnormal arrangement of the coronary arteries showed striking functional
similarities with atresia of the left main coronary artery. Current knowledge on
the morphogenesis of the coronary arteries suggests that the present anomalous
coronary artery pattern resulted from the penetration of the anticipated left
coronary artery system into the aorta at a totally erroneus site. This hindered
the normal development of the ostium, which subsisted as a punctiform,
practically nonfunctional opening.
PMID- 25851491
TI - Inf lammatory Mass with Fibrinoid Necrosis of Vessels Caused by Methylene Blue
Marking of a Colonic Polyp.
AB - Methylene blue is a relatively non-toxic dye that is used in a variety of
procedures including the marking of margins and skin flaps, identifying sinus and
fistulous tracts, localizing islet cell tumors, and marking colonic polyps. It
has been used intravascularly for the labeling of arteriovenous malformations or
to find small bleeding sites. Few adverse effects have been reported with its
use. We report an unusual case of an inflammatory mass secondary to transmural
injection of methylene blue that resulted in fibrinoid necrosis of arterial media
mimicking a necrotizing vasculitis.
PMID- 25851492
TI - Comparison of efficacy and toxicity profiles between paclitaxel/lobapoatin- and
cisplatin/5-fluorouracil-based concurrent chemoradiotherapy of advanced
inoperable oesophageal cancer.
AB - BACKGROUND AND AIM: Current chemoradiotherapy doesn't usually effectively control
oesophageal cancer progression. This study assessed the efficacy and toxicity
profiles of paclitaxel/lobaplatin (TL)- and cisplatin/5-fluorouracil (PF)-based
concurrent chemoradiotherapy (CCRT) in patients with advanced inoperable
oesophageal cancer. METHODS: A total of such 68 patients was recruited and
randomised to receive TL or PF-based CCRT. Radiotherapy was given at a total dose
of 60-70 Gy over 6 weeks. In the TL group of patients, paclitaxel 60 mg/m(2) was
administered intravenously on day 1, 8 and 15 and lobaplatin 30 mg/m(2) was
administered on day 2 in two cycles at 3-week intervals. In the PF group,
cisplatin 75 mg/m(2) was administered intravenously on day 1, and 5-fluorouracil
500 mg/m(2) and leucovorin 200 mg/m(2) were administered intravenously daily for
5 days in two cycles at 3-week intervals. Adverse events, treatment response and
follow-up data were collected. RESULTS: The treatment response rates were 73.53%
and 50.00% in the TL and PF groups respectively (P = 0.040). The median tumour
progression-free survival (PFS) was 13.0 and 6.5 months in the TL and PF groups
respectively (P = 0.034). Compared with PF group, the TL group demonstrated
decreased grade 3/4 nausea and vomiting (5.88% vs 35.29%, P = 0.003), decreased
granulocytopenia (11.76% vs 32.35%, P = 0.041) and platelet count reduction
(32.5% vs 8.8%, P = 0.016). CONCLUSIONS: The TL treatment regimen demonstrated
higher efficacy with less overall toxicity in patients with advanced inoperable
oesophageal cancer compared with the PF regimen. Further study is warranted to
validate our current observations.
PMID- 25851493
TI - Dynamic material flow modeling: an effort to calibrate and validate aluminum
stocks and flows in Austria.
AB - A calibrated and validated dynamic material flow model of Austrian aluminum (Al)
stocks and flows between 1964 and 2012 was developed. Calibration and extensive
plausibility testing was performed to illustrate how the quality of dynamic
material flow analysis can be improved on the basis of the consideration of
independent bottom-up estimates. According to the model, total Austrian in-use Al
stocks reached a level of 360 kg/capita in 2012, with buildings (45%) and
transport applications (32%) being the major in-use stocks. Old scrap generation
(including export of end-of-life vehicles) amounted to 12.5 kg/capita in 2012,
still being on the increase, while Al final demand has remained rather constant
at around 25 kg/capita in the past few years. The application of global
sensitivity analysis showed that only small parts of the total variance of old
scrap generation could be explained by the variation of single parameters,
emphasizing the need for comprehensive sensitivity analysis tools accounting for
interaction between parameters and time-delay effects in dynamic material flow
models. Overall, it was possible to generate a detailed understanding of the
evolution of Al stocks and flows in Austria, including plausibility evaluations
of the results. Such models constitute a reliable basis for evaluating future
recycling potentials, in particular with respect to application-specific
qualities of current and future national Al scrap generation and utilization.
PMID- 25851494
TI - A rapid and reliable strategy for chromosomal integration of gene(s) with
multiple copies.
AB - Direct optimization of the metabolic pathways on the chromosome requires tools
that can fine tune the overexpression of a desired gene or optimize the
combination of multiple genes. Although plasmid-dependent overexpression has been
used for this task, fundamental issues concerning its genetic stability and
operational repeatability have not been addressed. Here, we describe a rapid and
reliable strategy for chromosomal integration of gene(s) with multiple copies
(CIGMC), which uses the flippase from the yeast 2-MUm plasmid. Using green
fluorescence protein as a model, we verified that the fluorescent intensity was
in accordance with the integration copy number of the target gene. When a narrow
host-range replicon, R6K, was used in the integrative plasmid, the maximum
integrated copy number of Escherichia coli reached 15. Applying the CIGMC method
to optimize the overexpression of single or multiple genes in amino acid
biosynthesis, we successfully improved the product yield and stability of the
production. As a flexible strategy, CIGMC can be used in various microorganisms
other than E. coli.
PMID- 25851495
TI - Alteration in peripheral blood concentration of certain pro-inflammatory
cytokines in cows developing retention of fetal membranes.
AB - Retention of fetal membranes (RFM) adversely affects the production and
reproduction potential of the affected cows leading to huge economic loss.
Physiological separation of fetal membranes is reported to be an inflammatory
process. The present study compared the concentrations of certain pro
inflammatory cytokines [Interleukin 1beta (IL-1), Interleukin 6 (IL-6),
Interleukin 8 (IL-8) and Tumor necrosis factor alpha (TNF-alpha) between the cows
that developed RFM (n=10) and the cows that expelled fetal membranes normally
(n=10) to find out if they could serve as a predictive tool for RFM. Blood
samples were collected from the cows from 30 days before expected parturition
through day -21, day -14, day -7, day -5, day -3, day -1, on the day of
parturition (day 0), day 1 postpartum and the pro-inflammatory cytokines were
estimated in blood plasma by ELISA method. The IL-1beta concentration was
significantly lower (P<0.05) in cows that developed RFM compared to those that
expelled fetal membranes normally from 3 days before calving till the day of
calving. The plasma concentrations of IL-6 and IL-8 were also lower (P<0.05) in
cows that developed RFM than those calved normally. On the day of calving,
significantly (P<0.05) lower concentrations of TNF-alpha was observed in cows
that developed RFM compared to those expelled fetal membranes normally. It may be
inferred that the concentrations of IL-1, IL-6, IL-8 and TNF-alpha around
parturition were altered in cows developing RFM compared to those expelled fetal
membranes normally.
PMID- 25851496
TI - Prognostic factors affecting cervical adenocarcinoma: 10 years experience in a
single institution.
AB - OBJECTIVES: We performed a population-based study to determine the significance
of adenocarcinoma and to evaluate its behavior over the last 10 years among
patients treated in the National cancer institute of Morocco. STUDY DESIGN: This
is a retrospective study that was conducted in the national cancer institute of
Morocco. Over a period of 10 years, we retrieved 350 cases of cervical invasive
adenocarcinoma. Survival was analyzed according to the Kaplan-Meier method. A
univariate analysis of prognostic factors was performed using the test of log
rank. Cox regression model was used for the multivariate analysis of prognostic
factors. RESULTS: Mean age at presentation was 46 years. Sixty seven percent of
the patients had locally advanced stage. Radiotherapy was prescribed in 73.3 % of
the cases. The mean follow-up time for surviving patients was 51 months. The 5
year survival rates according to clinical stages were as follows, 76 and 62 % for
stages I and II, respectively, 32 and 9 % for stages III and IV, respectively.
Tumor stage, tumor grade, positive lymph nodes status, lymphovascular space
involvement and patient's age were significant prognostic factors in a univariate
analysis. While only stage and lymph node involvement remained significant
independent predictors for survival in the multivariate analysis. CONCLUSION:
Although in our country incidence of adenocarcinoma is lower than the ones
reported in western countries, in general our results are consistent with those
reported in the literature. Better outcomes are observed in both early stages and
young patients. Also, we found that FIGO stage, grade and lymph node metastases
to be significant prognostic factors for survival in cervical adenocarcinoma.
PMID- 25851497
TI - Dysregulated microRNAs involved in the progression of cervical neoplasm.
AB - PURPOSE: MicroRNAs (miRNAs) exhibit dysregulated expression in human cancer and
play an important role in carcinogenesis. The aim of this study was to identify a
distinct miRNA expression signature for cervical cancer and cervical
intraepithelial neoplasia (CIN) and to investigate the function of deregulated
miRNAs in cervical carcinoma. METHODS: A miRNA microarray was used to compare
miRNA expression profiles in cervical cancer, CIN and normal cervical tissues.
Real-time RT-PCR was used to validate the expression of 9 miRNAs in 103 cervical
tissues. Bioinformatics programs were used to predict potential target genes and
their function. Functional studies were performed to characterize the effect on
cervical cancer cells by overexpression of miR-218 and miR-21. RESULTS: We
identified deregulated miRNAs in cervical cancer and high-grade squamous
intraepithelial lesions (HSIL). MiR-218 was the most downregulated (0.175-fold
decrease) miRNA, and miR-21 was the most upregulated (5.67-fold increase) miRNA.
In addition, the expression patterns of 9 miRNAs were validated by real-time RT
PCR. Bioinformatics analyses and functional studies indicated that miR-218 and
miR-21 may be involved in cancer invasion and metastasis. CONCLUSION: Our study
demonstrated that miRNAs are aberrantly expressed in cervical cancer and cervical
preneoplastic lesions. These miRNAs may be involved in the progression of
cervical neoplasm as potential tumor suppressor genes or oncogenes.
PMID- 25851498
TI - Conflicting umbilical artery Doppler findings in fetuses with trisomy 21.
AB - OBJECTIVE: To assess differences between fetuses with isolated and non-isolated
trisomy 21 in umbilical artery (UA) Doppler findings in the second and third
trimester and to correlate those with placental histology. METHODS: Retrospective
analysis of UA pulsatility index (PI) in 281 fetuses with trisomy 21. Cases were
divided into isolated trisomy 21 (group I, n = 148, 52.7 %) and non-isolated
trisomy 21 (group II, n = 133, 47.3 %). UA measurements were evaluated in five
different time periods (A-E; <20 + 0 to >= 35 + 0 weeks) and were assigned
histopathology of the placenta. RESULTS: In 118/281 (42 %) cases, UA measurement
was abnormal. The frequency of PI values above the 95th percentile increased
significantly with gestational age in both groups (period A 32.9 % vs. period E
63.6 %, p < 0.0001). There was neither a difference in abnormal UA PI values
between isolated and non-isolated cases [37.8 % (56/148) vs. 46.6 % (62/133)] nor
a correlation to placental findings. CONCLUSIONS: Fetuses with trisomy 21 often
present with elevated UA PI in the late second or third trimester, irrespective
of small for gestational age growth, malformations or histopathological findings
of impaired placentation.
PMID- 25851499
TI - Large-Scale Computations in Chemistry: A Bird's Eye View of a Vibrant Field.
PMID- 25851500
TI - A probabilistic method for determining cortical dynamics during seizures.
AB - This work presents a probabilistic method for inferring the parameter ranges in a
biologically relevant mathematical model of the cortex most likely to be
producing seizures observed in an electrocorticogram (ECoG) signal from a human
subject. Additionally, this method produces a probabilistic pathway of the
temporal evolution of physiological state in the cortex over the course of
individual seizures, leveraging a model of the cortex that describes cortical
physiology. We describe ways in which these methods and results offer insights
into seizure etiology and have the potential to suggest new treatment options. To
directly account for the stochastic and noisy nature of the mathematical model
and the ECoG signal, we use a probabilistic Bayesian framework to map features of
ECoG segments onto a distribution of likelihoods over physiologically-relevant
parameter states. A Hidden Markov Model (HMM) is then introduced to incorporate
the belief that cortical physiology has both temporal continuity and also a
degree of reproducibility between individual seizures. By inspecting the ratio of
likelihoods between HMMs run under two possible parameter regions, both of which
produce seizures in the model, we determine which physiological parameter regions
are more likely to be causing the observed seizures. We show that between
individual seizures, there is consistency in these likelihood ratios between
hypothesized regions, in the temporal pathways calculated, and in the separation
of seizure from non-seizure time segment likelihood maps.
PMID- 25851501
TI - Egg shell quality in Japanese quail: characteristics, heritabilities and genetic
and phenotypic relationships.
AB - The objective of the present study was to estimate heritabilities as well as
genetic and phenotypic correlations for egg weight, specific gravity, shape
index, shell ratio, egg shell strength, egg length, egg width and shell weight in
Japanese quail eggs. External egg quality traits were measured on 5864 eggs of
934 female quails from a dam line selected for two generations. Within the
Bayesian framework, using Gibbs Sampling algorithm, a multivariate animal model
was applied to estimate heritabilities and genetic correlations for external egg
quality traits. The heritability estimates for external egg quality traits were
moderate to high and ranged from 0.29 to 0.81. The heritability estimates for egg
and shell weight of 0.81 and 0.76 were fairly high. The genetic and phenotypic
correlations between egg shell strength with specific gravity, shell ratio and
shell weight ranging from 0.55 to 0.79 were relatively high. It can be concluded
that it is possible to determine egg shell quality using the egg specific gravity
values utilizing its high heritability and fairly high positive correlation with
most of the egg shell quality traits. As a result, egg specific gravity may be
the choice of selection criterion rather than other external egg traits for
genetic improvement of egg shell quality in Japanese quails.
PMID- 25851502
TI - The effects of educational interventions on pharmacists' knowledge, attitudes and
beliefs towards low back pain.
AB - BACKGROUND: Practitioner beliefs and attitudes towards low back pain (LBP)
influence treatment decisions. Little is known about pharmacists' knowledge,
attitudes and beliefs towards LBP. OBJECTIVES: To investigate the effect of
educational interventions on pharmacists' knowledge, attitudes and beliefs
towards LBP. Setting Sydney Metropolitan Area. METHODS: Knowledge, attitudes and
beliefs was measured using the "Pharmacists' Back Beliefs Questionnaire", with
items from two previously reported questionnaires on back beliefs. Responses from
pharmacists attending a 2-h educational workshop on LBP (n = 204) and pharmacists
recruiting participants for a LBP clinical trial (n = 66) were compared to
responses from a control group of pharmacists (n = 65) to allow an evaluation of
the two interventions. Responses from workshop participants were also evaluated
before and after the session. Participants indicated their agreement with
statements about LBP on a 5-point Likert scale. Preferred responses were based on
guidelines for the evidence-based management of LBP. The primary analysis
evaluated total score on the nine-inevitability items of the Back Beliefs
Questionnaire ("inevitability score"). MAIN OUTCOME MEASURE: Inevitability score.
RESULTS: There was no significant difference in inevitability score between LBP
clinical trial pharmacists and the control group [mean difference (MD) 0.47 (95 %
CI -1.35 to 2.29; p = 0.61)]. The educational workshop led to a significant and
favourable change in inevitability score (MD 7.23 p < 0.001) and notable changes
in responses to misconceptions regarding bed rest and the need for imaging (p <
0.001) among participating pharmacists. CONCLUSIONS: Pharmacists attending the
educational workshop provided the most compelling evidence that education
specifically aimed at delivering evidence-based information can be successful in
changing practitioner knowledge, beliefs and attitudes towards LBP.
PMID- 25851503
TI - Antimicrobial stewardship activities in hospitals in Ireland and the United
Kingdom: a comparison of two national surveys.
AB - BACKGROUND: Best practice guidelines recommend that a multidisciplinary
Antimicrobial Management Team (AMT) conduct antimicrobial stewardship (AMS)
activities in hospitals. In order to continuously improve AMS activities in Irish
hospitals it is important to benchmark performance by comparison with other
countries. OBJECTIVE: To compare the membership of AMTs and AMS activities
conducted in Irish and United Kingdom (UK) hospitals. METHODS: A postal
questionnaire to determine the membership and activities of AMTs was issued to
the specialist antimicrobial pharmacist or pharmacist in charge at all Irish
Hospitals and all UK National Health Service Hospitals. The membership of AMTs
and the extent of AMS activities conducted were compared between the countries.
RESULTS: The response rates to the surveys were 73% (n = 51) in Ireland and 33%
in the UK (n = 273). 57% of Irish respondents reported having an AMT compared to
82% in the UK (p < 0.001). Significantly more AMTs in the UK had a specialist
antimicrobial pharmacist on the team (95% UK, 69% Ireland, p < 0.001). A higher
proportion of Irish respondents reported measuring the overall volume of
antimicrobial prescribing (Ireland 85%, UK 72%, p = 0.057). A higher proportion
of UK respondents reported measuring the appropriateness of antimicrobial
prescribing (76% UK, 58% Ireland, p = 0.019) and the appropriateness of
restricted antimicrobial prescribing (64% UK, 52% Ireland, p = 0.140).
CONCLUSION: Irish and UK AMTs need to be supported to recruit and retain
specialist antimicrobial pharmacists and to achieve higher rates of audit,
prescription appropriateness review and feedback activities.
PMID- 25851504
TI - Post-illness-onset risk of offending across the full spectrum of psychiatric
disorders.
AB - BACKGROUND: The link between psychotic disorders and violent offending is well
established; knowledge about risk of post-illness-onset offending across the full
spectrum of psychiatric disorders is lacking. We aimed to compare rates of any
offending and violent offending committed after the onset of illness, according
to diagnostic group, with population controls. METHOD: A 25% random sample of the
Danish population (n = 521 340) was followed from their 15th birthday until
offending occurred. Mental health status was considered as a time-varying
exposure in a Poisson regression model used to examine the duration from service
contact to the offence. RESULTS: Males with any psychiatric contact had an
incidence rate ratio (IRR) of 2.91 [95% confidence interval (CI) 2.80-3.02] for
any offending; 4.18 (95% CI 3.99-4.38) for violent offending. Associations were
stronger for women (IRR 4.17, 95% CI 3.95-4.40 for any offending; 8.02, 95% CI
7.20-8.94 for violent offending). Risk was similar across diagnostic groups for
any offending in males, while variation between diagnostic groups was seen for
male violent and female offending, both any and violent. CONCLUSIONS: Risk of
offending, particularly violent offending, was elevated across a range of mental
disorders following first contact with mental health services. The extent of
variation in strength of effect across diagnoses differed by gender.
PMID- 25851505
TI - Budgetary impact of the utilization of buprenorphine/naloxone sublingual film and
tablet for Medicaid in the United States.
AB - OBJECTIVES: The buprenorphine/naloxone combination for the treatment of opioid
dependence is available in a film or tablet formulation. Recent retrospective
studies demonstrated that treatment with the sublingual film formulation is
associated with improved treatment retention and lower healthcare costs. In March
2013, generic buprenorphine/naloxone tablets were approved in the US. A budget
impact model was built to compare healthcare expenditures for different market
shares of sublingual film and tablet. METHODS: A Markov model was developed to
track a cohort of opioid dependent patients treated with sublingual film or
tablet through the following treatment phases: initiation, maintenance,
discontinuation, off-treatment and reinitiation. Transition probabilities and
costs for each phase were estimated from the MarketScan Medicaid database for the
period between 1 March 2010 and 30 June 2012. The total expenditure for the plan
and expenditure per plan member per month were predicted over 5 years. Two market
share scenarios were considered: 1) sublingual film is progressively replaced by
generic tablet (current situation) and 2) the sublingual film holds a market
share of 100%. RESULTS: Predicted total costs over 5 years were $6400 million
when the sublingual film holds a market share of 100% (as per Scenario 2) which
is lower than when sublingual film is progressively replaced by generic tablet
(current situation as per Scenario 1) by $64 million. These savings were mostly
driven by inpatient care ($56 million saved over 5 years), followed by emergency
room care ($27 million) and pharmaceutical costs ($24 million). Costs of
outpatient care attenuated the difference as they were predicted to be higher by
$44 million in Scenario 2. The reduction in total cost per member per month
reached $0.027 in the fifth year. Results were most sensitive to price rebates
and to the probability of non-psychiatric hospitalization. CONCLUSIONS: While
using the sublingual film formulation for more patients treated with
buprenorphine/naloxone is predicted to increase outpatient care costs, it would
generate savings in emergency care and hospitalizations. In the treatment of
opioid dependence, total direct medical costs for Medicaid would be lower for
sublingual film treated patients, at current drug prices.
PMID- 25851506
TI - A Dynamical Basis Set for Generating Reaches.
AB - The motor cortex was the one of the first cortical areas to be explored
electrophysiologically, yet little agreement has emerged regarding its basic
response properties. Often it is assumed that single-neuron responses reflect a
preference for a particular movement or movement variable. It may be further
assumed that movement is generated by (or at least accompanied by) a growing
population-level preference for the relevant movement. This view has been
attractive because it provides a canonical form for the single neuron, a link
between preparatory and movement activity, a way of interpreting the population
response, and a platform for designing analyses and couching hypotheses. However,
this traditional view yields predictions that are at odds with basic features of
the data. We discuss an alternative simplified model, in which outgoing commands
are produced by dynamics that generate different output patterns as a function of
the initial preparatory state. For reaching tasks, we hypothesized simple
quasioscillatory dynamics because they provide a natural basis set for the
empirical patterns of muscle activity. The predictions of the dynamical model
match the data well at both the single-neuron and population levels, and the
quasioscillatory patterns explain many of the otherwise odd features of the
neural responses.
PMID- 25851508
TI - Pericardial effusion associated with hypothyroidism in an adult female with down
syndrome.
PMID- 25851507
TI - Computations in Sensorimotor Learning.
AB - Our cognitive abilities can only be expressed on the world through our actions.
Here we review the computations underlying the way that the sensorimotor system
converts both low-level sensory signals and high-level decisions into action,
focusing on the behavioral evidence for the theoretical frameworks. We review
recent work that determines how motor memories underlying sensorimotor learning
are activated and protected from interference, the role of Bayesian decision
theory in sensorimotor control including sources of suboptimality, the role of
risk sensitivity in guiding action, and how rapid motor responses may underlie
the robustness of the motor system to the vagaries of the world.
PMID- 25851509
TI - Isolation and characterization of a new [FeFe]-hydrogenase from Clostridium
perfringens.
AB - This paper reports the first characterization of an [FeFe]-hydrogenase from a
Clostridium perfringens strain previously isolated in our laboratory from a pilot
scale bio-hydrogen plant that efficiently produces H2 from waste biomasses. On
the basis of sequence analysis, the enzyme is a monomer formed by four domains
hosting various iron-sulfur centres involved in electron transfer and the
catalytic center H-cluster. After recombinant expression in Escherichia coli, the
purified protein catalyzes H2 evolution at high rate of 1645 +/- 16 s(-1) . The
optimal conditions for catalysis are in the pH range 6.5-8.0 and at the
temperature of 50 degrees C. EPR spectroscopy showed that the H-cluster of the
oxidized enzyme displays a spectrum coherent with the Hox state, whereas the CO
inhibited enzyme has a spectrum coherent with the Hox -CO state. FTIR
spectroscopy showed that the purified enzyme is composed of a mixture of redox
states, with a prevalence of the Hox ; upon reduction with H2 , vibrational modes
assigned to the Hred state were more abundant, whereas binding of exogenous CO
resulted in a spectrum assigned to the Hox -CO state. The spectroscopic features
observed are similar to those of the [FeFe]-hydrogenases class, but relevant
differences were observed given the different protein environment hosting the H
cluster.
PMID- 25851510
TI - The gene expression signature of anagrelide provides an insight into its
mechanism of action and uncovers new regulators of megakaryopoiesis.
AB - BACKGROUND: Anagrelide is a cytoreductive agent used to lower platelet counts in
essential thrombocythemia. Although the drug has been known to selectively
inhibit megakaryopoiesis for many years, the molecular mechanism accounting for
this activity is still unclear. OBJECTIVES AND METHODS: To address this issue we
have compared the global gene expression profiles of human hematopoietic cells
treated ex-vivo with and without anagrelide while growing under megakaryocyte
differentiation conditions, using high-density oligonucleotide microarrays. Gene
expression data were validated by the quantitative polymerase chain reaction and
mined to identify functional subsets and regulatory pathways. RESULTS: We
identified 328 annotated genes differentially regulated by anagrelide, including
many genes associated with platelet functions and with the control of gene
transcription. Prominent among the latter was TRIB3, whose expression increased
in the presence of anagrelide. Pathway analysis revealed that anagrelide up
regulated genes that are under the control of the transcription factor ATF4, a
known TRIB3 inducer. Notably, immunoblot analysis demonstrated that anagrelide
induced the phosphorylation of eIF2alpha, which is an upstream regulator of ATF4,
and increased ATF4 protein levels. Furthermore, salubrinal, an inhibitor of
eIF2alpha dephosphorylation, increased the expression of ATF4-regulated genes and
blocked megakaryocyte growth. CONCLUSIONS: These findings link signaling through
eIF2alpha/ATF4 to the anti-megakaryopoietic activity of anagrelide and identify
new potential modulators of megakaryopoiesis.
PMID- 25851512
TI - Effect of sleep deprivation on the electrophysiological signature of habituation
to noxious laser stimuli.
AB - BACKGROUND: Sleep deprivation induces hyperalgesia. However, this pro-nociceptive
effect is not reflected at the electrophysiological level, since sleep restricted
subjects show amplitude reduction of Laser-evoked Potentials (LEP). We aimed to
explore the contribution of habituation to this paradoxical LEP amplitude
decline. METHODS: We compared LEP's of 12 healthy students (23.2 +/- 1.1 years)
after habitual sleep (HS) and a night of total sleep deprivation (TSD). Twelve
repetitive laser stimulus blocks (each comprising twenty stimuli) were applied
under three attention conditions ('focusing' - 'neutral' - 'distraction'
condition). Stimulus blocks were split in part 1 (stimulus 1-10) and part 2
(stimulus 11-20). The contribution of habituation to the TSD-induced LEP
amplitude decline was studied by calculating the percentage amplitude reduction
of part 2 as compared to part 1. Individual sleepiness levels were correlated
with (1) averaged LEP's and (2) the degree of habituation. RESULTS: TSD induced
hyperalgesia to laser stimuli (p < 0.001). In contrast, depending on the
attention condition, the P2 amplitude of the N2P2-complex was significantly
reduced ('focusing': p = 0.004; 'neutral': p = 0.017; distraction: p = 0.71).
Habituation of the P2 amplitude to radiant heat was increased after TSD
('focusing': p = 0.04; 'neutral': p < 0.001; distraction: p = 0.88). TSD had no
significant effect on N1 amplitudes (p > 0.05). Individual sleepiness correlated
negatively with averaged P2 amplitudes (p = 0.02), but not with the degree of
habituation (p = 0.14). CONCLUSION: TSD induces hyperalgesia and results in
attention-dependent enhanced habituation of the P2 component. Increased
habituation may--to a substantial degree--explain the TSD-induced LEP-amplitude
decline. For this article, a commentary is available at the Wiley Online Library.
PMID- 25851511
TI - The Impact of Left Atrial Surface Area and the Second Generation Cryoballoon on
Clinical Outcome of Atrial Fibrillation Cryoablation.
AB - AIMS: In this observational study, we examine the significance of the left atrial
(LA) surface area and compare the clinical usage of the Arctic Front Advance
(CBA) versus Arctic Front (CB) cryoballoon with the intent to investigate the
impact of each in terms of long-term freedom from atrial fibrillation (AF) for
patients with nonvalvular AF. METHODS: Pulmonary vein isolation (PVI) was
performed while using a cryoballoon ablation catheter in conjunction with an
intraluminal circular diagnostic mapping catheter, Achieve. The consecutive
patients ablated with CBA were matched with patients previously ablated with CB,
using propensity score matching. The primary endpoint of this observational
single-center retrospective study was the first observation of electrocardiogram
documented recurrence of atrial arrhythmias lasting >30 seconds. RESULTS: The
patient demographic data were similar in the CBA- and CB-group (N = 188 patients
each group). In all patients in the CBA-group and in 95% of the patients in the
CB group, acute procedural PVI of all veins was achieved with the single usage of
a 28-mm cryoballoon. The one-year freedom from atrial arrhythmias was
significantly better in the CBA- versus the CB-group of patients, 90% versus 64%,
respectively. During 15-month clinical follow-up in CBA group, patients with LA
area above 23 cm(2) were more likely to experience recurrence of AF (23%) than
patients with LA area below 23 cm(2) (7%). CONCLUSIONS: Comparing one-year
outcomes, the CBA is superior to the CB with regards to maintenance of normal
sinus rhythm. When using the CBA catheter, an enlarged LA is associated with a
higher recurrence of arrhythmia.
PMID- 25851514
TI - Synthesis of non-natural sequence-encoded polymers using phosphoramidite
chemistry.
AB - Sequence-defined non-natural polyphosphates were prepared using iterative
phosphoramidite protocols on a polystyrene solid support. Three monomers were
used in this work: 2-cyanoethyl (3-dimethoxytrityloxy-propyl)
diisopropylphosphoramidite (0), 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl
propyl) diisopropylphosphoramidite (1), and 2-cyanoethyl (3-dimethoxytrityloxy
2,2-dipropargyl-propyl) diisopropylphosphoramidite (1'). Phosphoramidite coupling
steps allowed rapid synthesis of homopolymers and copolymers. In particular, the
comonomers (0, 1), (0, 1'), and (1, 1') were used to synthesize sequence-encoded
copolymers. It was found that long encoded sequences could be easily built using
phosphoramidite chemistry. ESI-HRMS, MALDI-HRMS, NMR, and size exclusion
chromatography analyses indicated the formation of monodisperse polymers with
controlled comonomer sequences. The polymers obtained with the comonomers (0, 1')
and (1, 1') were also modified by copper-catalyzed azide-alkyne cycloaddition
with a model azide compound, namely 11-azido-3,6,9-trioxaundecan-1-amine. (1)H
and (13)C NMR analysis evidenced quantitative modification of the alkyne side
chains of the monodisperse copolymers. Thus, the molecular structure of the
coding monomer units can be easily varied after polymerization. Altogether, the
present results open up interesting avenues for the design of information
containing macromolecules.
PMID- 25851513
TI - Mathematical Models to Explore Potential Effects of Supersaturation and
Precipitation on Oral Bioavailability of Poorly Soluble Drugs.
AB - Poorly soluble drugs are increasingly formulated into supersaturating drug
delivery systems which may precipitate during oral delivery. The link between in
vitro drug concentration profiles and oral bioavailability is under intense
investigation. The objective of the present work was to develop closed-form
analytical solutions that relate in vitro concentration profiles to the amount of
drug absorbed using several alternate assumptions and only six parameters. Three
parameters define the key features of the in vitro drug concentration-time
profile. An additional three parameters focus on physiological parameters.
Absorption models were developed based on alternate assumptions; the drug
concentration in the intestinal fluid: (1) peaks at the same time and
concentration as in vitro, (2) peaks at the same time as in vitro, or (3) reaches
the same peak concentration as in vitro. The three assumptions provide very
different calculated values of bioavailability. Using Case 2 assumptions,
bioavailability enhancement was found to be less than proportional to in silico
examples of dissolution enhancement. Case 3 assumptions lead to bioavailability
enhancements that are more than proportional to dissolution enhancements. Using
Case 1 predicts drug absorption amounts that fall in between Case 2 and 3. The
equations developed based on the alternate assumptions can be used to quickly
evaluate the potential improvement in bioavailability due to intentional
alteration of the in vitro drug concentration vs. time curve by reformulation.
These equations may be useful in making decisions as to whether reformulation is
expected to provide sufficient bioavailability enhancement to justify the effort.
PMID- 25851515
TI - A Force to Be Reckoned With: A Review of Synthetic Microswimmers Powered by
Ultrasound.
AB - Synthetic microswimmers are a class of artificial nano- or microscale particle
capable of converting external energy into motion. They are similar to natural
microswimmers such as bacteria in behavior and are, therefore, of great interest
to the study of active matter. Additionally, microswimmers show promise in
applications ranging from bioanalytics and environmental monitoring to particle
separation and drug delivery. However, since their sizes are on the nano
/microscale and their speeds are in the MUm s(-1) range, they fall into a low
Reynolds number regime where viscosity dominates. Therefore, new propulsion
schemes are needed for these microswimmers to be able to efficiently move.
Furthermore, many of the hotly pursued applications call for innovations in the
next phase of development of biocompatible microswimmers. In this review, the
latest developments of microswimmers powered by ultrasound are presented.
Ultrasound, especially at MHz frequencies, does little harm to biological samples
and provides an advantageous and well-controlled means to efficiently power
microswimmers. By critically reviewing the recent progress in this research
field, an introduction of how ultrasound propels colloidal particles into
autonomous motion is presented, as well as how this propulsion can be used to
achieve preliminary but promising applications.
PMID- 25851516
TI - Purification and characterization of a trypsin inhibitor from the seeds of
Artocarpus heterophyllus Lam.
AB - A proteinaceous inhibitor against trypsin was isolated from the seeds of
Artocarpus heterophyllus Lam. by successive ammonium sulfate precipitation, ion
exchange, and gel-filtration chromatography. The trypsin inhibitor, named as
AHLTI (A. heterophyllus Lam. trypsin inhibitor), consisted of a single
polypeptide chain with a molecular weight of 28.5 kDa, which was confirmed by
sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel-filtration
chromatography. The N-terminal sequence of AHLTI was DEPPSELDAS, which showed no
similarity to other known trypsin inhibitor sequence. AHLTI completely inhibited
bovine trypsin at a molar ratio of 1:2 (AHLTI:trypsin) analyzed by native
polyacrylamide gel electrophoresis, inhibition activity assay, and gel-filtration
chromatography. Moreover, kinetic enzymatic studies were carried out to
understand the inhibition mechanism of AHLTI against trypsin. Results showed that
AHLTI was a competitive inhibitor with an equilibrium dissociation constant (Ki)
of 3.7 * 10(-8) M. However, AHLTI showed weak inhibitory activity toward
chymotrypsin and elastase. AHLTI was stable over a broad range of pH 4-8 and
temperature 20-80 degrees C. The reduction agent, dithiothreitol, had no obvious
effect on AHLTI. The trypsin inhibition assays of AHLTI toward digestive enzymes
from insect pest guts in vitro demonstrated that AHLTI was effective against
enzymes from Locusta migratoria manilensis (Meyen). These results suggested that
AHLTI might be a novel trypsin inhibitor from A. heterophyllus Lam. belonging to
Kunitz family, and play an important role in protecting from insect pest.
PMID- 25851517
TI - Zebrafish phosvitin is an antioxidant with non-cytotoxic activity.
AB - Antioxidants, or anti-oxidant agents, have attracted a great deal of attention in
recent years because of their roles in prevention of chronic diseases and
utilization as preservatives in food and cosmetics. In this study, we clearly
demonstrated that zebrafish recombinant phosvitin (rPv) is an antioxidant agent
capable of inhibiting the oxidation of the linoleic acid, and scavenging the 2,2
diphenyl-1-picrylhydrazyl radical. We also showed that zebrafish rPv is a
cellular antioxidant capable of protecting radical-mediated oxidation of cellular
biomolecules. Importantly, zebrafish rPv is non-cytotoxic to murine macrophage
RAW264.7 cells. It is the first report that showed the antioxidant activities of
Pv in fishes, suggesting that zebrafish Pv can be an important antioxidant, which
can be used as preservatives in food and cosmetics and even as supplementary
mediator in different diseased states.
PMID- 25851520
TI - Editorial comment on paper by Naguib, et al. 'A single-center strategy to
minimize blood transfusion in neonates and children undergoing cardiac surgery'.
PMID- 25851521
TI - What is the condition of education in Pediatric Anesthesiology?
PMID- 25851522
TI - Reply to Dr. Haydar regarding his comment: caudal clonidine and apnea risk.
PMID- 25851523
TI - Fluid resuscitation for toddlers and young children.
PMID- 25851524
TI - Carbon monoxide has antinociceptive effects in rodent models of pain.
PMID- 25851525
TI - Spontaneous fungal peritonitis: a devastating complication of cirrhosis.
AB - Spontaneous bacterial peritonitis is a well-known complication of cirrhosis;
however, spontaneous fungal peritonitis (SFP) is less well-recognised and
described. Our objective was to determine the clinical characteristics, treatment
outcomes and factors associated with death among patients with SFP. We performed
a retrospective cohort study using the primary outcome of all-cause mortality at
28 days. Twenty-five patients were included; Candida species were the causative
pathogen in all cases. At the onset of SFP, patients were critically ill, median
APACHE II and MELD scores were 22 and 30.3, respectively. The 28-day mortality
rate was 56%; six patients died prior to culture positivity. Among the remaining
patients, there were no differences in rates of death by treatment regimen (P =
0.55). APACHE II score at the onset of SFP was an independent predictor of death
(OR = 1.46, 95% CI = 1.02-2.08, P = 0.04). In conclusion, SFP develops among
critically ill patients with cirrhosis and is associated with high rates of
death. Directed antifungal therapy did not improve patient outcomes. Future
studies assessing the benefit of early or pre-emptive antifungal therapy are
warranted.
PMID- 25851526
TI - The effect of dietary arachidonic acid (ARA) on growth performance, fatty acid
composition and expression of ARA metabolism-related genes in larval half-smooth
tongue sole (Cynoglossus semilaevis).
AB - The present study was conducted to investigate the effects of dietary arachidonic
acid (ARA) on growth performance, fatty acid composition and ARA metabolism
related gene expression in larval half-smooth tongue sole (Cynoglossus
semilaevis). Larvae (35 d after hatching, 54 (SEM 1) mg) were fed diets with
graded concentrations of ARA (0.01, 0.39, 0.70, 1.07, 1.42 and 2.86 % dry weight)
five times per d to apparent satiation for 30 d. Results showed that increased
dietary ARA concentration caused a significant non-linear rise to a plateau in
survival rate, final body weight and thermal growth coefficient, and the maximum
values occurred with the 1.42 % ARA treatment. As dietary ARA increased to 1.07
or 1.42 %, activities of trypsin, leucine aminopeptidase and alkaline phosphatase
levels increased, but they decreased with higher ARA concentrations. The fatty
acid composition of tongue sole larvae was almost well correlated with their
dietary fatty acid profiles, and the EPA content of the larvae decreased with
increasing dietary ARA. Meanwhile, the partial sequences of COX-1a (cyclo
oxygenase-1a), COX-1b (cyclo-oxygenase-1b), COX-2 (cyclo-oxygenase-2), 5-LOX (5
lipoxygenase) and CYP2J6-like (cytochrome P450 2J6-like) were also obtained. Both
COX-2 and 5-LOX mRNA expression levels significantly increased to a plateau in an
'L'-shaped manner as dietary ARA increased to 1.07 or 1.42 %, but no significant
differences were found in the gene expression of COX-1a, COX-1b or CYP2J6-like.
These results suggest that 1.07-1.42 % dietary ARA was beneficial to the growth
performance of larval tongue sole, and the regulation of dietary ARA on the
growth performance of larvae was probably involved in altering the mRNA
expression of COX-2 and 5-LOX.
PMID- 25851527
TI - Distinct higher-order alpha-synuclein oligomers induce intracellular aggregation.
AB - Misfolding and aggregation of alpha-synuclein (alpha-syn) into Lewy bodies is
associated with a range of neurological disorders, including Parkinson's disease
(PD). The cell-to-cell transmission of alpha-syn pathology has been linked to
soluble amyloid oligomer populations that precede Lewy body formation. Oligomers
produced in vitro under certain conditions have been demonstrated to induce
intracellular aggregation in cell culture models. In the present study, we
characterize, by ESI-ion mobility spectrometry (IMS)-MS, a specific population of
alpha-syn oligomers. These MS-compatible oligomers were compared with oligomers
with known seeding and pore-forming capabilities and were shown to have the
ability to induce intracellular aggregation. Each oligomer type was shown to have
distinct epitope profiles that correlated with their toxic gain-of-function.
Structurally, the MS compatible oligomers populated a range of species from
dimers through to hexamers. Lower-order oligomers were structurally diverse and
consistent with unstructured assemblies. Higher-order oligomers were shown to be
compact with ring-like structures. The observation of this compact state may
explain how this natively disordered protein is able to transfer pathology from
cell to cell and avoid degradation by cellular proteases.
PMID- 25851528
TI - Body language: The interplay between positional behavior and gestural signaling
in the genus Pan and its implications for language evolution.
AB - OBJECTIVES: The gestural repertoires of bonobos and chimpanzees are well
documented, but the relationship between gestural signaling and positional
behavior (i.e., body postures and locomotion) has yet to be explored. Given that
one theory for language evolution attributes the emergence of increased gestural
communication to habitual bipedality, this relationship is important to
investigate. MATERIALS AND METHODS: In this study, we examined the interplay
between gestures, body postures, and locomotion in four captive groups of bonobos
and chimpanzees using ad libitum and focal video data. RESULTS: We recorded 43
distinct manual (involving upper limbs and/or hands) and bodily (involving
postures, locomotion, head, lower limbs, or feet) gestures. In both species,
actors used manual and bodily gestures significantly more when recipients were
attentive to them, suggesting these movements are intentionally communicative.
Adults of both species spent less than 1.0% of their observation time in bipedal
postures or locomotion, yet 14.0% of all bonobo gestures and 14.7% of all
chimpanzee gestures were produced when subjects were engaged in bipedal postures
or locomotion. Among both bonobo groups and one chimpanzee group, these were
mainly manual gestures produced by infants and juvenile females. Among the other
chimpanzee group, however, these were mainly bodily gestures produced by adult
males in which bipedal posture and locomotion were incorporated into
communicative displays. DISCUSSION: Overall, our findings reveal that bipedality
did not prompt an increase in manual gesturing in these study groups. Rather,
body postures and locomotion are intimately tied to many gestures and certain
modes of locomotion can be used as gestures themselves.
PMID- 25851530
TI - Fast preparation of a highly efficient organic monolith via photo-initiated thiol
ene click polymerization for capillary liquid chromatography.
AB - A novel organic monolith was firstly prepared in a UV-transparent fused-silica
capillary by a single-step approach via photo-initiated thiol-ene click
polymerization reaction of 1,2,4-trivinylcyclohexane (TVCH) and pentaerythriol
tetra(3-mercaptopropionate) (4SH) within 10min. The effects of both composition
of prepolymerization solution and polymerization time on the morphology and
permeability of monolithic column were investigated in detail. Then, the optimal
condition was acquired to fabricate a homogeneous and permeable organic monolith.
The chemical groups of the monolithic column were confirmed by Fourier transform
infrared spectroscopy (FT-IR). The SEM graphs showed the organic monolith
possessed a uniform porous structure, which promotes the highest column
efficiency of ~133,000 plates per meter for alkylbenzenes at the linear velocity
of 0.65mm/s in reversed-phase liquid chromatography. Finally, the organic
monolithic column was further applied for separation of basic compounds,
pesticides and EPA610, indicating satisfactory separation ability.
PMID- 25851531
TI - Cerebrolysin reverses hippocampal neural atrophy in a mice model of diabetes
mellitus type 1.
AB - The animal model of streptozotocin-induced diabetes mellitus type 1 (DM1) is used
to study neuronal and behavioral changes produced by an increase in blood-glucose
levels. Our previous report showed that chronic streptozotocin administration
induced atrophy of dendritic morphology of pyramidal neurons of the CA1 dorsal
hippocampus. In addition, we showed that Cerebrolysin (Cbl), a neurotrophic
peptide mixture, reduces the dendritic atrophy in animal models of aging. This
study aimed to determine whether Cbl was capable of reducing behavioral and
neuronal alterations, after 6 weeks of hyperglycemia in mice (streptozotocin
induced DM1). The levels of glucose in the blood were evaluated before and after
streptozotocin administration and only animals with more than 240 mg/dL of blood
levels of glucose were used. After streptozotocin treatment, the mice received 6
weeks of Cbl, locomotor activity was measured and dendritic morphological changes
were evaluated using Golgi-Cox stain procedure, and analyzed by the Sholl method.
In mice treated with streptozotocin there was a clear reduction in the dendritic
length of pyramidal neurons of the CA1 and granular cells of the dental gyrus of
the dorsal hippocampus. Interestingly, Cbl reversed the morphological changes
induced by streptozotocin. Our results extend the list of abnormal morphological
changes detected in this model of DM, and support the possibility that Cbl may
have beneficial effects in the management of brain alterations induced by DM.
PMID- 25851532
TI - Extracellular Streptomyces lividans vesicles: composition, biogenesis and
antimicrobial activity.
AB - We selected Streptomyces lividans to elucidate firstly the biogenesis and
antimicrobial activities of extracellular vesicles that a filamentous and highly
differentiated Gram-positive bacterium produces. Vesicle types range in diameter
from 110 to 230 nm and 20 to 60 nm, respectively; they assemble to clusters, and
contain lipids and phospholipids allowing their in situ imaging by specific
fluorescent dyes. The presence of the identified secondary metabolite
undecylprodigiosin provokes red fluorescence of a portion of the heterogeneous
vesicle populations facilitating in vivo monitoring. Protuberances containing
vesicles generate at tips, and alongside of substrate hyphae, and enumerate
during late vegetative growth to droplet-like exudates. Owing to in situ imaging
in the presence and absence of a green fluorescent vancomycin derivative, we
conclude that protuberances comprising vesicles arise at sites with enhanced
levels of peptidoglycan subunits [pentapeptide of lipid II (C55)-linked
disaccharides], and reduced levels of polymerized and cross-linked peptidoglycan
within hyphae. These sites correlate with enhanced levels of anionic
phospholipids and lipids. Vesicles provoke pronounced damages of Aspergillus
proliferans, Verticillium dahliae and induced clumping and distortion of
Escherichia coli. These harmful effects are likely attributable to the action of
the identified vesicular compounds including different enzyme types, components
of signal transduction cascades and undecylprodigiosin. Based on our pioneering
findings, we highlight novel clues with environmental implications and
application potential.
PMID- 25851533
TI - Detecting outlying trials in network meta-analysis.
AB - Network meta-analysis (NMA) expands the scope of a conventional pairwise meta
analysis to simultaneously handle multiple treatment comparisons. However, some
trials may appear to deviate markedly from the others and thus be inappropriate
to be synthesized in the NMA. In addition, the inclusion of these trials in
evidence synthesis may lead to bias in estimation. We call such trials trial
level outliers. To the best of our knowledge, while heterogeneity and
inconsistency in NMA have been extensively discussed and well addressed, few
previous papers have considered the proper detection and handling of trial-level
outliers. In this paper, we propose several Bayesian outlier detection measures,
which are then applied to a diabetes data set. Simulation studies comparing our
approaches in both arm-based and contrast-based model settings are provided in
two supporting appendices.
PMID- 25851534
TI - Factors influencing delivered mean airway pressure during nasal CPAP with the RAM
cannula.
AB - OBJECTIVE: To measure mean airway pressure (MAP) delivered through the RAM
Cannula(r) when used with a ventilator in CPAP mode as a function of percent
nares occlusion in a simulated nasal interface/test lung model and to compare the
results to MAPs using a nasal continuous positive airway pressure (NCPAP)
interface with nares fully occluded. STUDY DESIGN: An artificial airway model was
connected to a spontaneous breathing lung model in which MAP was measured at set
NCPAP levels between 4 and 8 cmH2 O provided by a Drager Evita XL(r) ventilator
and delivered through three sizes of RAM cannulae. Measurements were performed
with varying leakage at the nasal interface by decreasing occlusion from 100% to
29%, half-way prong insertion, and simulated mouth leakage. Comparison
measurements were made using the Drager BabyFlow(r) NCPAP interface with a full
nasal seal. RESULTS: With simulated mouth closed, the Drager interface delivered
MAPs within 0.5 cmH2 O of set CPAP levels. For the RAM cannula, with 60-80% nares
occlusion, overall delivered MAPs were 60 +/- 17% less than set CPAP levels (P <
0.001). Further, MAP decreased progressively with decreasing percent nares
occlusion. The simulated open mouth condition resulted in significantly lower
MAPs to <1.7 cmH2 O. The one-half prong insertion depth condition, with closed
mouth, yielded MAPs approximately 35 +/- 9% less than full insertion pressures (P
< 0.001). CONCLUSIONS: In our bench tests, the RAM interface connected to a
ventilator in NCPAP mode failed to deliver set CPAP levels when applied using the
manufacturer recommended 60-80% nares occlusion, even with closed mouth and full
nasal prong insertion conditions.
PMID- 25851535
TI - ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T
lymphocytes for enhanced anti-tumor immunotherapy.
AB - PD-1 negatively regulates CD8(+) cytotoxic T lymphocytes (CTL) cytotoxicity and
anti-tumor immunity. However, it is not fully understood how PD-1 expression on
CD8(+) CTL is regulated during anti-tumor immunotherapy. In this study, we have
identified that the ADAP-SKAP55 signaling module reduced CD8(+) CTL cytotoxicity
and enhanced PD-1 expression in a Fyn-, Ca(2+)-, and NFATc1-dependent manner. In
DC vaccine-based tumor prevention and therapeutic models, knockout of SKAP55 or
ADAP showed a heightened protection from tumor formation or metastases in mice
and reduced PD-1 expression in CD8(+) effector cells. Interestingly, CTLA-4
levels and the percentages of tumor infiltrating CD4(+)Foxp3(+) Tregs remained
unchanged. Furthermore, adoptive transfer of SKAP55-deficient or ADAP-deficient
CD8(+) CTLs significantly blocked tumor growth and increased anti-tumor immunity.
Pretreatment of wild-type CD8(+) CTLs with the NFATc1 inhibitor CsA could also
downregulate PD-1 expression and enhance anti-tumor therapeutic efficacy.
Together, we propose that targeting the unrecognized ADAP-SKAP55-NFATc1-PD-1
pathway might increase efficacy of anti-tumor immunotherapy.
PMID- 25851536
TI - New insights into the pathology of pulmonary hypertension: implication of the miR
210/ISCU1/2/Fe-S axis.
AB - Elevated pulmonary arterial pressure in patients with pulmonary hypertension (PH)
is mainly caused by increased pulmonary vascular resistance (PVR), due primarily
to sustained pulmonary vasoconstriction and excessive pulmonary vascular
remodeling. According to the current classification, PH has been classified into
five categories based on etiology (Simonneau et al, 2013). Among them, group 1 or
pulmonary arterial hypertension (PAH) is a rare but progressive and deadly
disease affecting ~1-10 per 1 million people. Despite expanding treatment options
to ameliorate patients' symptoms, PAH remains a devastating disease with a poor
long-term prognosis.
PMID- 25851537
TI - Regulation of hematogenous tumor metastasis by acid sphingomyelinase.
AB - Metastatic dissemination of cancer cells is the ultimate hallmark of malignancy
and accounts for approximately 90% of human cancer deaths. We investigated the
role of acid sphingomyelinase (Asm) in the hematogenous metastasis of melanoma
cells. Intravenous injection of B16F10 melanoma cells into wild-type mice
resulted in multiple lung metastases, while Asm-deficient mice (Smpd1(-/-) mice)
were protected from pulmonary tumor spread. Transplanting wild-type platelets
into Asm-deficient mice reinstated tumor metastasis. Likewise, Asm-deficient mice
were protected from hematogenous MT/ret melanoma metastasis to the spleen in a
mouse model of spontaneous tumor metastasis. Human and mouse melanoma cells
triggered activation and release of platelet secretory Asm, in turn leading to
ceramide formation, clustering, and activation of alpha5beta1 integrins on
melanoma cells finally leading to adhesion of the tumor cells. Clustering of
integrins by applying purified Asm or C16 ceramide to B16F10 melanoma cells
before intravenous injection restored trapping of tumor cells in the lung in Asm
deficient mice. This effect was revertable by arginine-glycine-aspartic acid
peptides, which are known inhibitors of integrins, and by antibodies neutralizing
beta1 integrins. These findings indicate that melanoma cells employ platelet
derived Asm for adhesion and metastasis.
PMID- 25851538
TI - Vasculotide reduces endothelial permeability and tumor cell extravasation in the
absence of binding to or agonistic activation of Tie2.
AB - Angiopoietin-1 (Ang1) activation of Tie2 receptors on endothelial cells (ECs)
reduces adhesion by tumor cells (TCs) and limits junctional permeability to TC
diapedesis. We hypothesized that systemic therapy with Vasculotide (VT)-a
purported Ang1 mimetic, Tie2 agonist-can reduce the extravasation of potentially
metastatic circulating TCs by similarly stabilizing the host vasculature. In
vitro, VT and Ang1 treatments impeded endothelial hypermeability and the
transendothelial migration of MDA-MB-231?LM2-4 (breast), HT29 (colon), or SN12
(renal) cancer cells to varying degrees. In mice, VT treatment inhibited the
transit of TCs through the pulmonary endothelium, but not the hepatic or
lymphatic endothelium. In the in vivo LM2-4 model, VT monotherapy had no effect
on primary tumors, but significantly delayed distant metastatic dissemination to
the lungs. In the post-surgical adjuvant treatment setting, VT therapeutically
complemented sunitinib therapy, an anti-angiogenic tyrosine kinase inhibitor
which limited the local growth of residual disease. Unexpectedly, detailed
investigations into the putative mechanism of action of VT revealed no evidence
of Tie2 agonism or Tie2 binding; alternative mechanisms have yet to be
determined.
PMID- 25851539
TI - Usefulness of core needle biopsy for thyroid nodules with macrocalcifications:
comparison with fine-needle aspiration.
AB - BACKGROUND: This study was performed to determine the benefits of core needle
biopsy (CNB), as compared with fine-needle aspiration (FNA), for the diagnosis of
thyroid nodules with macrocalcifications. MATERIALS AND METHODS: The
institutional review board approved this retrospective study, and informed
consent was waived. From February 2010 to March 2012, the study included 147
thyroid nodules with macrocalcification of 145 consecutive patients who underwent
simultaneous FNA and CNB for each nodule. Diagnostic accuracy and inconclusive
diagnoses, including nondiagnostic reading and atypia of undetermined
significance or follicular lesion of undetermined significance reading were
compared among FNA, CNB, and a combination of FNA and CNB (FNA/CNB) using
McNemar's test; the benefits of CNB were calculated. RESULTS: Compared to FNA,
CNB and FNA/CNB showed fewer inconclusive diagnoses (FNA vs. CNB: 62/147 [42.2%]
vs. 14/147 [9.5%], p<0.001; FNA vs. FNA/CNB: 62/147 [42.2%] vs. 14/147 [9.5%],
p<0.001), resulting in the avoidance of repeat FNA or diagnostic surgery in 48 of
62 patients (77.4%, respectively in CNB and FNA/CNB) who would have undergone
these procedures if only FNA was performed. Compared to FNA, FNA/CNB showed
higher sensitivity and accuracy (sensitivity: 23/32 [71.9%] vs. 31/32 [96.9%],
p=0.008; accuracy: 77/86 [89.5%] vs. 85/86 [98.8%], p=0.008), resulting in
avoidance of delayed surgery in eight of nine patients (88.9%) with thyroid
cancer in whom the surgery would have been missed if FNA only had been performed.
CONCLUSION: In the workup of thyroid nodules with macrocalcification, compared
with FNA alone, FNA/CNB decreases inconclusive diagnoses and increases
sensitivity, thereby reducing repeated FNA procedures, diagnostic surgeries, and
delayed therapeutic surgeries.
PMID- 25851541
TI - Nonsuppurative Nodular Panniculitis of the Breast.
PMID- 25851542
TI - Glycated albumin is more closely correlated with coronary artery disease than 1,5
anhydroglucitol and glycated hemoglobin A1c.
AB - BACKGROUND: The aim of this study was to investigate the associations of two
nontraditional glycemic markers, glycated albumin (GA) and 1,5-anhydroglucitol
(1,5-AG), as well as glycated hemoglobin A1c (HbA1c) with coronary artery disease
(CAD). METHODS: In total, 272 subjects (178 men and 94 postmenopausal women) were
enrolled in this study. All of them underwent coronary angiography which was used
to diagnose CAD. The severity of coronary artery stenosis was assessed by the
coronary stenosis index (CSI). GA and 1,5-AG were assayed using the enzymatic
method, and HbA1c was detected by high-pressure liquid chromatography. RESULTS:
The HbA1c and GA levels were significantly higher in CAD group than those in non
CAD group (both P < 0.01). While the 1,5-AG level was significantly lower in CAD
group than that in non-CAD group (P < 0.05). After adjustment for traditional
risk factors of CAD, HbA1c, 1,5-AG, and GA, multivariate logistic regression
analysis showed that GA was an independent risk factor for CAD (odds ratio =
1.143, 95% confidence interval: 1.048-1.247, P = 0.002). With CSI as a dependent
variable, multiple stepwise regression analysis demonstrated an independent
positive correlation between GA and CSI (standardized beta = 0.184, P = 0.003),
beyond gender, age, and lipid-lowering therapy, after adjustment for traditional
risk factors of CAD, HbA1c, 1,5-AG, and GA. CONCLUSIONS: GA was more closely
correlated with CAD than HbA1c and 1,5-AG in a Chinese population with high risk
of CAD.
PMID- 25851543
TI - Rigid multibody simulation of a helix-like structure: the dynamics of bacterial
adhesion pili.
AB - We present a coarse-grained rigid multibody model of a subunit assembled helix
like polymer, e.g., adhesion pili expressed by bacteria, that is capable of
describing the polymer's force-extension response. With building blocks
representing individual subunits, the model appropriately describes the complex
behavior of pili expressed by the gram-negative uropathogenic Escherichia coli
bacteria under the action of an external force. Numerical simulations show that
the dynamics of the model, which include the effects of both unwinding and
rewinding, are in good quantitative agreement with the characteristic force
extension response as observed experimentally for type 1 and P pili. By tuning
the model, it is also possible to reproduce the force-extension response in the
presence of anti-shaft antibodies, which dramatically changes the mechanical
properties. Thus, the model and results in this work give enhanced understanding
of how a pilus unwinds under the action of external forces and provide a new
perspective of the complex bacterial adhesion processes.
PMID- 25851544
TI - Clinical-scale purification of pluripotent stem cell derivatives for cell-based
therapies.
AB - Human pluripotent stem cells (hPSCs) have the potential to revolutionize cell
replacement therapies because of their ability to self renew and differentiate
into nearly every cell type in the body. However, safety concerns have delayed
the clinical translation of this technology. One cause for this is the capacity
that hPSCs have to generate tumors after transplantation. Because of the
challenges associated with achieving complete differentiation into clinically
relevant cell types, the development of safe and efficient strategies for
purifying committed cells is essential for advancing hPSC-based therapies.
Several purification strategies have now succeeded in generating non-tumorigenic
and homogeneous cell-populations. These techniques typically enrich for cells by
either depleting early committed populations from teratoma-initiating hPSCs or by
positively selecting cells after differentiation. Here we review the working
principles behind separation methods that have facilitated the safe and
controlled application of hPSC-derived cells in laboratory settings and pre
clinical research. We underscore the need for improving and integrating
purification strategies within differentiation protocols in order to unlock the
therapeutic potential of hPSCs.
PMID- 25851545
TI - Trans-aortic endoscopic ventricular thrombectomy in a patient with HIT and
concomitant Aortic and ventricular thromboses.
AB - Dual aortic and ventricular thrombi are rare following myocardial infraction. We
report the case of a 56-year-old man who initially denied primary percutaneous
coronary intervention as a result of psychological phobia. Initial
pharmacological management by thrombolysis and heparin was followed by multiple
arterial thromboses including those of the left ventricle and right iliac artery
with a subsequent diagnosis of heparin-induced thrombocytopaenia. Ensuing
surgical management revealed the unanticipated finding of an additional aortic
sinus thrombosis that was excised. The left ventricular thrombus was removed
endoscopically to prevent ventricular incisions. This case emphasizes the
technical advantages of video-endoscopic management of intracardiac thrombi and
highlights the unexpected nature of multiple thromboses associated with heparin
induced thrombocytopaenia.
PMID- 25851546
TI - Uncommon non-Hodgkin lymphomas of childhood: pathological diagnosis, clinical
features and treatment approaches.
AB - We provide a review of the pathological and clinical features for uncommon B-cell
and T-cell lymphomas of childhood with a specific focus on advances in treatment
approaches and outcomes. There is clearly a need for prospective investigation of
both the clinical and biological features of the uncommon non-Hodgkin lymphoma
subtypes in childhood. These results should lead to more uniform and more
effective treatment approaches.
PMID- 25851547
TI - Association between mental disorders and physical diseases in adolescents from a
nationally representative cohort.
AB - OBJECTIVE: Pediatric health care and research focus mostly on single morbidities,
although the single-disease framework has been challenged. The main objective was
to estimate associations between childhood mental disorders and physical
diseases. METHODS: This study is based on weighted data (n = 6482) from the
National Comorbidity Survey Replication Adolescent Supplement (age, 13-18 years).
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition lifetime
mental disorders were assessed using the fully structured World Health
Organization Composite International Diagnostic Interview, complemented by parent
report. Lifetime medical conditions and doctor-diagnosed diseases were assessed
by adolescent self-report. RESULTS: Of 6469 participants, 2137 (35.33%) reported
at least one mental disorder and one physical disease. The most substantial
associations included those between affective disorders and diseases of the
digestive system (odds ratio [OR] = 3.46, 95% confidence interval [CI] = 2.28
5.24), anxiety disorders and arthritis (OR = 2.27, CI = 1.34-3.85), anxiety
disorders and heart diseases (OR = 2.41, CI = 1.56-3.73), anxiety disorders and
diseases of the digestive system (OR = 2.18, CI = 1.35-3.53), and eating
disorders and epilepsy/seizures (OR = 5.45, CI = 1.57-18.87). Sociodemographic
factors did not account for the association between mental disorders and physical
diseases. CONCLUSIONS: Findings suggest that mental disorders and physical
diseases often co-occur in childhood. This association is a major public health
challenge, and the child health system needs additional strategies in patient
centered care, research, medical education, health policy, and economics to
develop well-coordinated interdisciplinary approaches linking mental and physical
care in children.
PMID- 25851548
TI - Use of CSF alpha-synuclein in the differential diagnosis between Alzheimer's
disease and other neurodegenerative disorders.
AB - BACKGROUND: The etiology and pathogenesis of neurodegenerative disorders has yet
to be elucidated, so their differential diagnosis is a challenge. This is
especially true in differentiating Alzheimer's disease (AD), dementia with Lewy
bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA). METHODS:
A total of 11 eligible articles were identified by search of electronic databases
including PubMed, Springer Link, Elsevier, and the Cochrane Library, up to June
2014. In meta-analyses, standardized mean differences (SMD), with 95% confidence
intervals (CI), comparing cerebrospinal fluid (CSF) measures of alpha-synuclein
between the above conditions were calculated using random-effects models.
RESULTS: CSF alpha-synuclein concentrations were significantly higher in AD
compared to DLB [SMD: 0.32, 95% CI: (0.02, 0.62), z = 2.07, P = 0.038]; PD [SMD:
0.87, 95% CI: (0.15, 1.58), z = 2.38, P = 0.017]; or MSA [SMD: 1.14, 95% CI:
(0.15, 2.14), z = 2.25, P = 0.025]. However, no significant difference was found
between patients with AD and neurological cognitively normal controls [SMD: 0.02,
95% CI: (-0.21, 0.24), z = 0.13, P = 0.894]. CONCLUSIONS: Results of these meta
analysis suggest that quantification of CSF alpha-synuclein could help
distinguish AD from other neurodegenerative disorders such as DLB, PD, or MSA.
PMID- 25851549
TI - Scorpion-related cardiomyopathy: Clinical characteristics, pathophysiology, and
treatment.
AB - CONTEXT: Scorpion envenomation is a threat to more than 2 billion people
worldwide with an annual sting number exceeding one million. Acute heart failure
presenting as cardiogenic shock or pulmonary edema, or both is the most severe
presentation of scorpion envenomation accounting for 0.27% lethality rate.
OBJECTIVE: The purpose of this review is to characterize the scorpion-related
cardiomyopathy, clarify its pathophysiological mechanisms, and describe
potentially useful treatments in this particular context. METHODS: We searched
major databases on observational or interventional studies (whether clinical or
experimental) on the cardiorespiratory consequences of scorpion envenomation and
their treatment. No limit of age or language was imposed. A critical appraisal of
the literature was conducted in order to provide a pathophysiological scheme that
reconciles reported patterns of cardiovascular toxicity and hypotheses and
assumptions made so far. RESULTS: Early cardiovascular dysfunction is related to
the so-called "vascular phase" of scorpion envenomation, which is related to a
profound catecholamine-related vasoconstriction leading to a sharp increase in
left ventricular (LV) afterload, thereby impeding LV emptying, and increasing LV
filling pressure. Following this vascular phase, a myocardial phase occurs,
characterized by a striking alteration in LV contractility (myocardial stunning),
low cardiac output, and hypotensive state. The right ventricle involvement is
symmetric to that of LV with a profound and reversible alteration in right
ventricular performance. This phase is unique in that it is reversible
spontaneously or under inotropic treatment. Scorpion myocardiopathy combines the
features of takotsubo myocardiopathy (or stress myocardiopathy) which is linked
to a massive release in catecholamines leading to myocardial ischemia through
coronary vasomotor abnormalities (epicardial coronary spasm and/or increase in
coronary microvascular resistance). Treatment of pulmonary edema due to scorpion
envenomation follows the same principles as those applied for the treatment of
cardiogenic pulmonary edema in general: this begins with oxygen supplementation
targeting an oxygen saturation of 92% or more, by oxygen mask, continuous
positive airway pressure, noninvasive ventilation, or conventional mechanical
ventilation. Dobutamine effectively improves hemodynamic parameters and may
reduce mortality in severe scorpion envenomation. CONCLUSION: Scorpion
cardiomyopathy is characterized by a marked and reversible alteration in
biventricular performance. Supportive treatment relying on ventilatory support
and dobutamine infusion is a bridge toward recovery in the majority of patients.
PMID- 25851550
TI - Association of Physician Certification Policy and Quality of Care: Evidence of
percutaneous coronary intervention certification program in Taiwan.
AB - OBJECTIVES: The aim of this study was to compare procedural, short-term and two
year outcomes of percutaneous coronary intervention (PCI) between board-certified
and non-board certified interventional cardiologists in Taiwan. BACKGROUND: Most
studies of associations between quality and certification have analyzed
populations in the Western developed countries. METHODS: This retrospective
population-based study analyzed 2057 patients who had received PCI in 11
hospitals in 2007. The outcome measures were procedural, 30-day, and 2-year
adverse events. RESULTS: Sixty certified physicians performed 1771 PCI procedures
whereas 84 non-certified physicians performed 286 procedures. Patients treated by
non-certified physicians had significantly higher rates of in-hospital mortality
(6.99% vs. 2.82%, respectively; p <= 0.001) and same-stay CABG (1.40% vs. 0.06%,
respectively; p <= 0.001). The results of multilevel logistic regression and Cox
multivariate regression indicated that patients treated by non-certified
physicians also had higher probabilities of in-hospital death (OR=2.92, 95% CI:
1.20-7.08) and two-year death (hazard ratio, 1.63; 95% confidence interval, 1.18
2.24). CONCLUSIONS: This is the first study in Asia in investigating the
association between board certification policy and surgical outcomes, and the
results confirmed that the board certification policy is also effective for Asian
population. The policy implications of these findings are discussed.
PMID- 25851551
TI - Safety testing and operational procedures for self-developed radiofrequency
coils.
AB - The development of novel radiofrequency (RF) coils for human ultrahigh-field (>=7
T), non-proton and body applications is an active field of research in many MR
groups. Any RF coil must meet the strict requirements for safe application on
humans with respect to mechanical and electrical safety, as well as the specific
absorption rate (SAR) limits. For this purpose, regulations such as the
International Electrotechnical Commission (IEC) standard for medical electrical
equipment, vendor-suggested test specifications for third party coils and custom
developed test procedures exist. However, for higher frequencies and shorter
wavelengths in ultrahigh-field MR, the RF fields may become extremely
inhomogeneous in biological tissue and the risk of localized areas with elevated
power deposition increases, which is usually not considered by existing safety
testing and operational procedures. In addition, important aspects, such as risk
analysis and comprehensive electrical performance and safety tests, are often
neglected. In this article, we describe the guidelines used in our institution
for electrical and mechanical safety tests, SAR simulation and verification, risk
analysis and operational procedures, including coil documentation, user training
and regular quality assurance testing, which help to recognize and eliminate
safety issues during coil design and operation. Although the procedure is
generally applicable to all field strengths, specific requirements with regard to
SAR-related safety and electrical performance at ultrahigh-field are considered.
The protocol describes an internal procedure and does not reflect consensus among
a large number of research groups, but rather aims to stimulate further
discussion related to minimum coil safety standards. Furthermore, it may help
other research groups to establish their own procedures. Copyright (c) 2015 John
Wiley & Sons, Ltd.
PMID- 25851552
TI - Vaginal Yolk Sac Tumor in an Infant: A Case Report and Literature Review of the
Last 30 Years.
AB - Vaginal yolk sac tumor is a rare malignant germ-cell tumor occurring most
commonly in young girls. The treatment has evolved over the last 3 decades from
radical surgery to conservative surgery with chemotherapy to chemotherapy alone.
Here we present a case of a 6-month-old girl successfully treated with upfront
surgery followed by chemotherapy. We include a literature review of studies on
vaginal yolk sac tumor published in the last 30 years. We discuss the role of
upfront surgery where possible followed by chemotherapy as a safe alternative to
chemotherapy alone for the treatment of this rare malignancy.
PMID- 25851553
TI - ABO Group as a Thrombotic Risk Factor in Children With Acute Lymphoblastic
Leukemia: A Retrospective Study of 523 Patients.
AB - Children with acute lymphoblastic leukemia (ALL) are at high risk of thrombotic
complications, resulting from multiple risk factors (malignancy, chemotherapy,
central venous access devices, and inherent host characteristics). Non-O blood
groups have been associated with an increased risk of venous thromboembolism
(VTE) in adults, with a compounding effect in the presence of thrombophilia or
cancer. We hypothesized that among children with ALL receiving a standardized
protocol, there would be an increased risk of thrombotic events in non-O compared
with O blood group patients. In a retrospective study of 523 children with ALL
from June 1995 to April 2013, there were 56 (10.7%) thromboembolic events.
Patients with VTE were compared with the whole cohort, based on blood group, age,
sex, leukemia phenotype, and clinical risk category. Among children with VTE, 42
(75%) had non-O and 14 (25%) had O blood group, compared with 302 (57.7%) non-O
and 221 (42.3%) O blood groups in the cohort. Non-O blood group was confirmed as
an independent risk factor for VTE in multivariate analysis. This is the first
study to report a significant association between non-O blood groups and VTE in
children with cancer.
PMID- 25851554
TI - Large Cell Neuroendocrine Carcinoma of the Nasopharynx: A Pediatric Case.
AB - Neuroendocrine tumors are rare, preferentially located in the gastrointestinal
tract or in the lungs. We present the case of a 9-year-old child, presenting with
a tissue mass involving the nasopharynx and associated with multiple pulmonary
and bone metastases. The immunohistochemical analysis showed a proliferation of
large tumor cells stained with Chromogranin A and Synaptophysin. The diagnosis of
multimetastatic large cell neuroendocrine carcinoma was made. This tumor is
infrequent in this location and particularly in children. This case describes the
pathologic aspects and immunohistochemical results and presents a discussion of
the differential diagnoses.
PMID- 25851555
TI - Pediatric Pharyngeal IgD-positive Monoclonal Plasmacytoid and Plasma Cell
Neoplasm.
AB - Pediatric neoplasm with monoclonal proliferation of lymphoplasmacytoid
lymphocytes and plasma cells is exceedingly rare and has essentially never been
reported in immunocompetent children. Here, we report a previously healthy 13
year-old girl with a pharyngeal mass and enlarged cervical lymph nodes. The
pharyngeal mass was composed of CD138, CD79a, MUM-1, IgD, CD20, PAX-5, CD43,
lambda-restricted monoclonal plasmacytoid, and plasma cells. Scattered CD20, PAX
5 B cells were present in the background. The patient was treated as localized
non-Hodgkin lymphoma (stage II) with cyclophosphamide, doxorubicin, vincristine,
and prednisone and is in complete remission at 17 months from the last
chemotherapy.
PMID- 25851556
TI - A Sporadic Case of Advanced Metastatic Cholangiocarcinoma in a Child: A Case
Report and Review of Literature.
AB - Cholangiocarcinoma (CC) is a malignancy of the biliary tract that commonly
presents in the seventh decade of life, but is extremely rare in children. We
report on a sporadic case of malignant CC in an 11-year-old female. Originally
presenting with dyspnea, chest x-ray identified multiple pulmonary metastases,
and various imaging modalities revealed diffuse disease spread throughout the
liver and lungs. Following pathologic diagnosis of CC, aggressive treatment was
initiated with a dramatic initial response to chemotherapy, however, as often
occurs with advanced disease in adults, this patient ultimately succumbed to the
disease.
PMID- 25851557
TI - Fatal Acute Myeloid Leukemia With 11q23 MLL Gene Rearrangement Following
Mitoxantrone Treatment in a Case of Childhood-onset Multiple Sclerosis.
PMID- 25851558
TI - Adolescent reactions to icon-driven response modes in a tablet-based health
screening tool.
AB - Increasingly popular touch-screen electronic tablets offer clinics a new medium
for collecting adolescent health screening data in the waiting area before
visits, but there has been limited evaluation of interactive response modes. This
study investigated the clarity, comprehensibility, and utility of icon-driven and
gestural response functions employed in one such screening tool, TickiT. We
conducted cognitive processing interviews with 30 adolescents from Vancouver
(aged 14-20 years, 60% female, 30% English as a second language) as they
completed the TickiT survey. Participants used seven different interactive
functions to respond to questions across 30 slides, while being prompted to
articulate their thoughts and reactions. The audio-recorded, transcribed
interviews were analyzed for evidence of comprehension, nuances in response
choices, and youth interest in the modes. Participants were quite receptive to
the icon response modes. Across demographics and cultural backgrounds, they
indicated question prompts were clear, response choices appropriate, and response
modes intuitive. Most said they found the format engaging and would be more
inclined to fill out such a screening tool than a paper-and-pencil form in a
clinical setting. Given the positive responses and ready understanding of these
modes among youth, clinicians may want to consider interactive icon-driven
approaches for screening.
PMID- 25851559
TI - Clinical Decision Support and Perioperative Peripheral Nerve Injury: A Quality
Improvement Project.
AB - Decision support at the point of care has been demonstrated to be an effective
tool in providing a safe environment and improving patient outcomes. The
operating room is typically an area where advanced technology is introduced to
nurses on a regular basis. This quality improvement project focused on preventing
a peripheral nerve injury, which is an example of a postoperative adverse event
that is considered preventable. Injury of a peripheral nerve is the result of
compression, hyperextension, flexion, or ischemia surrounding the nerve. The
goals for this project were to improve the knowledge of peripheral nerve injury
of the operating room nurses, design and implement a peripheral nerve injury
assessment screen that could provide decision support within the operating room
record, improve the nursing documentation of peripheral nerve injury
interventions, and (long term) decrease the incidence of peripheral nerve injury.
A decision support screen within the operating room record was designed to
supplement the operating room nurse's risk assessment for peripheral nerve
injury. The components of this project involved a preliminary and postproject
surveys on peripheral nerve injury knowledge, an educational presentation, and a
retrospective random review of nursing documentation in the operating room
electronic health records. Project results demonstrated a significant increase in
nursing documentation of peripheral nerve injury interventions (63%-92%) and a
positive attitude toward their exposure to basic decision support (P = .046).
Recommendations for future studies and establishing a standardized coding system
for peripheral nerve injury identification were identified.
PMID- 25851560
TI - Laying the Groundwork for NCLEX Success: An Exploration of Adaptive Quizzing as
an Examination Preparation Method.
AB - First-time NCLEX-RN pass rates are an important indicator of nursing school
success and quality. Nursing schools use different methods to anticipate NCLEX
outcomes and help prevent student failure and possible threat to accreditation.
This study evaluated the impact of a shift in NCLEX preparation policy at a BSN
program in the southeast United States. The policy shifted from the use of
predictor score thresholds to determine graduation eligibility to a more
proactive remediation strategy involving adaptive quizzing. A descriptive
correlational design evaluated the impact of an adaptive quizzing system designed
to give students ongoing active practice and feedback and explored the
relationship between predictor examinations and NCLEX success. Data from student
usage of the system as well as scores on predictor tests were collected for three
student cohorts. Results revealed a positive correlation between adaptive
quizzing system usage and content mastery. Two of the 69 students in the sample
did not pass the NCLEX. With so few students failing the NCLEX, predictability of
any course variables could not be determined. The power of predictor examinations
to predict NCLEX failure could also not be supported. The most consistent factor
among students, however, was their content mastery level within the adaptive
quizzing system. Implications of these findings are discussed.
PMID- 25851561
TI - Extracorporeal Treatment in Severe Hypertriglyceridemia-Induced Pancreatitis.
AB - Plasmapheresis is a well-accepted treatment option in severe hypertriglyceridemia
induced pancreatitis (HTGP). The rationale behind this approach is the depletion
of triglycerides and the reduction of inflammatory cytokines. The time span
between onset of clinical symptoms and start of plasmapheresis might have an
important impact on mortality. Hyperviscosity of patients' plasma represents
another special challenge for the applied separation technology. The procedures
can be performed either by centrifugal device (CFD) or membrane based (MBS)
units. The present study reports the outcome of 10 patients suffering from HTG.
The expected mortality of the collective was 25%. Plasmapheresis was started
after an average 16.3 h (SD +/- 6.7 h) after onset of symptoms. No mortality
occurred. Apheresis was statistically equally effective with both devices. A
median of 3 sessions reduced the TG level to normal and correlated with patients'
improvement. During follow up, three patients developed a pancreatic pseudocyst
requiring surgical intervention without further complication.
PMID- 25851562
TI - Combining malaria control with house electrification: adherence to recommended
behaviours for proper deployment of solar-powered mosquito trapping systems,
Rusinga Island, western Kenya.
AB - OBJECTIVE: To investigate community adherence to recommended behaviours for
proper deployment of solar-powered mosquito trapping systems (SMoTS) after 3- to
10-week use. METHODS: Solar-powered mosquito trapping system, which also provided
power for room lighting and charging mobile phones, were installed in houses in
Rusinga Island, western Kenya. We used a structured checklist for observations
and a semi-structured questionnaire for interviews in 24 homesteads. We also
analysed the subject of 224 community calls to the project team for technical
maintenance of SMoTS. RESULTS: Most respondents cared for SMoTS by fencing,
emptying and cleaning the trap. Our observations revealed that most traps were
fenced, clean and in good working condition. A significantly higher proportion of
community calls was lighting-related. Lighting was the main reason respondents
liked SMoTS because it reduced or eliminated expenditure on kerosene. However,
some respondents observed they no longer heard sounds of mosquitoes inside their
houses. All respondents reportedly slept under insecticide-treated nets (ITNs)
before receiving SMoTS. After receiving SMoTS, most respondents reportedly
continued to use ITNs citing that the project advised them to do so. Some beach
residents stopped using ITNs because they no longer heard mosquitoes or due to
heat discomfort caused by lights. CONCLUSION: Electricity-related incentives
played a greater role in encouraging adherence to recommended behaviours for
proper deployment of SMoTS than the potential health benefits in the early stages
of the intervention. Although energy-related financial incentives may play a
role, they are insufficient to ensure adherence to health advice, even in the
short term. Ongoing community engagement and research monitors and addresses
adherence to recommended behaviours including continuation of current malaria
control strategies.
PMID- 25851563
TI - Relationship between azathioprine dosage, 6-thioguanine nucleotide levels, and
therapeutic response in pediatric patients with IBD treated with azathioprine.
AB - BACKGROUND: Azathioprine (AZA) is commonly used to treat IBD either alone or in
combination with mesalazine. However, there are relatively few studies concerning
the relationship between AZA dose, thiopurine metabolite levels, and therapeutic
response in pediatric patients treated with both AZA and mesalazine. METHODS: We
retrospectively investigated the relationship between AZA dose, thiopurine
metabolite levels, and therapeutic response in 137 pediatric patients with IBD
treated with AZA using multilevel analysis. Additional factors affecting
metabolite levels and therapeutic response were also analyzed. RESULTS: A
positive correlation was observed between AZA dosage and 6-thioguanine nucleotide
(6-TGN) level (P < 0.0001). Variant TPMT genotype (P < 0.001) and concomitant use
of mesalazine (P < 0.001) were predictors of higher 6-TGN levels. Leukopenia (P =
0.025) and lymphopenia (P = 0.045) were associated with higher levels of 6-TGN.
Poor AZA compliance affected median 6-TGN levels (P < 0.001). The frequency of
patients with median 6-TGN levels >235 pmol per 8 * 10(8) red blood cells was the
highest in the sustained therapeutic response group (P = 0.015). Age, sex, IBD
type, and duration of AZA therapy did not influence 6-TGN levels or therapeutic
effect. CONCLUSIONS: AZA dosage is positively correlated with 6-TGN level. Higher
6-TGN levels are related to leukopenia, lymphopenia, and concurrent use of
mesalazine. These results provide the rationale for monitoring metabolites to
optimize drug dosing and minimize drug-related toxicity. In addition, maintenance
of 6-TGN levels within a beneficial therapeutic range by direct monitoring should
be helpful in attaining therapeutic efficacy, although this possibility should be
verified in prospective studies.
PMID- 25851564
TI - Predicting Endoscopic Crohn's Disease Activity Before and After Induction Therapy
in Children: A Comprehensive Assessment of PCDAI, CRP, and Fecal Calprotectin.
AB - BACKGROUND: Mucosal healing (MH) is a vital early endpoint in management of
Crohn's disease (CD). MH depends on endoscopic assessment and there is increasing
interest in non-invasive proxies, Pediatric Crohn's Disease activity Index
(PDCAI), C-reactive protein (CRP) and fecal calprotectin (FC). These proxies must
be validated against endoscopic disease activity (SES-CD) at diagnosis and after
induction therapy in well characterized cohorts of children with CD. METHODS: A
prospective cohort of 24 newly diagnosed children (<16 yr) with luminal CD
quantifiable on complete ileo-colonoscopy had paired PCDAI, CRP, FC and SES-CD at
diagnosis and after 8 weeks therapy with exclusive enteral nutrition or steroids.
RESULTS: At diagnosis: PCDAI had poor correlation (r = 0.33); CRP (r = 0.54) and
FC (r = 0.46) had moderate correlation with SES-CD. After induction therapy:
11/24 had inactive disease (SES-CD 0-2); PCDAI (r = 0.34) and CRP (0.28) had poor
correlation with SES-CD, many children with SES-CD >=3 having normalization of
both PCDAI and CRP. FC had good correlation (r = 0.50) but many with SES-CD 0-2
had FC >200 MUg/gm stool. FC<500 (positive likelihood ratio, 3.2) and FC drop
>50% (positive likelihood ratio, 3.8) had greater predictive value for inactive
disease. Composite PCDAI (<10), CRP (<5 mg/dl) & FC <500 MUg had excellent
Negative LR (0.2) predicting inactive disease. CONCLUSIONS: PCDAI is unreliable
for endoscopic disease severity assessment. Only FC correlates with endoscopic
activity after therapy but cut off <200 MUg is too high for defining endoscopic
recovery in children. Composite normalized PCDAI, CRP and FC <500 MUg should be
considered the non-invasive endpoint for treatment response in pediatric CD.
PMID- 25851565
TI - A functional ruthenium(ii) complex for imaging biothiols in living bodies.
AB - A unique ruthenium(ii) complex, [Ru(bpy)2(DNS-bpy)](PF6)2 [bpy: 2,2'-bipyridine,
DNS-bpy: 4-(2,4-dinitrophenylthio)-2,2'-bipyridine], that can act as a probe for
the recognition and luminescence sensing of biothiols has been designed and
synthesized. Due to the presence of effective photo-induced electron transfer
(PET) from the potent electron donor (Ru-bpy centre) to the strong electron
acceptor (2,4-dinitrophenyl moiety), the Ru(ii) complex itself is weakly
luminescent. Reaction of [Ru(bpy)2(DNS-bpy)](PF6)2 with biothiols leads to the
replacement of the 2,4-dinitrophenyl moiety by biothiols, which results in the
loss of PET within the complex, to allow recovery of the MLCT-based emission of
the Ru(ii) complex with an 80-fold increase in luminescence intensity. Taking
advantage of the high specificity and sensitivity, and the excellent
photophysical properties of Ru(ii) complexes, [Ru(bpy)2(DNS-bpy)](PF6)2 was
successfully applied to the luminescence imaging of biothiols in living Daphnia
magna. The results demonstrated the practical applicability of [Ru(bpy)2(DNS
bpy)](PF6)2 as a luminescent probe for the monitoring of biothiols in living
bodies.
PMID- 25851566
TI - SMT or TOFT? How the two main theories of carcinogenesis are made (artificially)
incompatible.
AB - The building of a global model of carcinogenesis is one of modern biology's
greatest challenges. The traditional somatic mutation theory (SMT) is now
supplemented by a new approach, called the Tissue Organization Field Theory
(TOFT). According to TOFT, the original source of cancer is loss of tissue
organization rather than genetic mutations. In this paper, we study the
argumentative strategy used by the advocates of TOFT to impose their view. In
particular, we criticize their claim of incompatibility used to justify the
necessity to definitively reject SMT. First, we note that since it is difficult
to build a non-ambiguous experimental demonstration of the superiority of TOFT,
its partisans add epistemological and metaphysical arguments to the debate. This
argumentative strategy allows them to defend the necessity of a paradigm shift,
with TOFT superseding SMT. To do so, they introduce a notion of incompatibility,
which they actually use as the Kuhnian notion of incommensurability. To justify
this so-called incompatibility between the two theories of cancer, they move the
debate to a metaphysical ground by assimilating the controversy to a fundamental
opposition between reductionism and organicism. We show here that this
argumentative strategy is specious, because it does not demonstrate clearly that
TOFT is an organicist theory. Since it shares with SMT its vocabulary, its
ontology and its methodology, it appears that a claim of incompatibility based on
this metaphysical plan is not fully justified in the present state of the debate.
We conclude that it is more cogent to argue that the two theories are compatible,
both biologically and metaphysically. We propose to consider that TOFT and SMT
describe two distinct and compatible causal pathways to carcinogenesis. This view
is coherent with the existence of integrative approaches, and suggests that they
have a higher epistemic value than the two theories taken separately.
PMID- 25851567
TI - Major changes to care system need to be properly funded to succeed, warn
charities.
PMID- 25851568
TI - Transparent and luminescent ionogels composed of Eu(3+)-coordinated ionic liquids
and poly(methyl methacrylate).
AB - We report here on transparent and luminescent ionogels that consist of ionic
ternary europium (III) complexes and the inexpensive non-toxic compound,
poly(methyl methacrylate) (PMMA) and that were formed by dissolving these
complexes in methacrylate (MMA) monomers followed by in situ polymerization. The
resulting ionogels show a bright red emission under near-UV light irradiation.
Luminescence data confirm the energy transfer from terpyridine-functionalized
ionic liquid to Eu(3+) ions.
PMID- 25851570
TI - The mystique of veins revisited.
PMID- 25851572
TI - Editor's note.
PMID- 25851571
TI - Phlebosclerosis, phlebothrombosis, and thrombophlebitis: A current perspective.
AB - Phlebosclerosis, phlebothrombosis, and thrombophlebitis are three fundamentally
different structural changes affecting superficial, deep, visceral, and cerebral
veins. Phlebosclerosis is a frequent, age-dependent fibrotic degeneration of one
or all three wall layers. It does not represent a distinct disease entity but may
impair the venous function and contribute to the development of thrombosis.
Phlebothrombosis represents a serious circulatory disorder. It may be due to a
variety of factors including phlebitis, i.e., a primary inflammatory disease of
the venous wall. Thrombophlebitis may be a relatively harmless disorder, such as
represented by idiopathic skipping phlebitis (phlebitis saltans), or it may be a
symptom of an underlying systemic disease. Whereas phlebothrombosis in
nonvaricose veins is suspicious of an underlying malignancy or a coagulation
disorder, thrombophlebitis is not related to malignancies but may accompany
Buerger's disease or other systemic vasculitides. The histopathological
distinction of phlebothrombosis and thrombophlebitis is therefore of paramount
importance and determines further clinical investigations. A proposal for
classification of thrombophlebitides and some guidelines for clinicopathological
differentiation of the various types of phlebitides are presented.
PMID- 25851569
TI - The Use of Induced Pluripotent Stem Cell Technology to Advance Autism Research
and Treatment.
AB - Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental
disorders sharing a core set of symptoms, including impaired social interaction,
language deficits, and repetitive behaviors. While ASDs are highly heritable and
demonstrate a clear genetic component, the cellular and molecular mechanisms
driving ASD etiology remain undefined. The unavailability of live patient
specific neurons has contributed to the difficulty in studying ASD
pathophysiology. The recent advent of induced pluripotent stem cells (iPSCs) has
provided the ability to generate patient-specific human neurons from somatic
cells. The iPSC field has quickly grown, as researchers have demonstrated the
utility of this technology to model several diseases, especially neurologic
disorders. Here, we review the current literature around using iPSCs to model
ASDs, and discuss the notable findings, and the promise and limitations of this
technology. The recent report of a nonsyndromic ASD iPSC model and several
previous ASD models demonstrating similar results points to the ability of iPSC
to reveal potential novel biomarkers and therapeutics.
PMID- 25851573
TI - Introduction International meeting on chagasic heart disease: South American
Italian Cooperation on a vital cardiologic issue.
PMID- 25851574
TI - Pathogenesis of chronic Chagas' myocarditis: An overview.
AB - The evidence provided by both human and animal studies on chronic Chagas' heart
disease suggests that the development of the chronic fibrosing myocarditis is
related to progressive and additive focal cellular necrosis with associated
inflammatory lymphomononuclear infiltrate, reactive and reparative myocardial
fibrosis, surrounding myocyte hypertrophy. These processes may be initiated and
perpetuated by alterations in the myocardial microcirculation and by autoimmune
factors. These findings could foster future therapeutic strategies in the
management of chronic chagasic patients to optimize the medical treatment and
hopefully to improve prognosis.
PMID- 25851575
TI - Chagas' disease: Microvascular and interstitial matrix abnormalities
characteristic of congestive cardiomyopathy of diverse etiology.
AB - Chagas' disease, due to a chronic and persistent infection with the parasite
Trypanosoma cruzi, is the cause of one of the most prevalent forms of congestive
cardiomyopathy in South and Central America. In common with other congestive
cardiomyopathies due to acquired and hereditary etiologies seen worldwide,
chagasic cardiomyopathy is characterized by cardiomegaly, ventricular chamber
remodeling, myocellular necrosis, and multifocal areas of interstitial and
replacement fibrosis. The microscopic presence of the parasite in the late stages
of the disease is rare. This review examines some of the evidence for the role of
a dysfunctional microvasculature as a pathophysiological mechanism for myocardial
damage in chagasic cardiomyopathy. Perturbations of the interstitial connective
tissue matrix in Chagas' disease also are described in regard to the remodeling
characteristic of the affected ventricle. Similar abnormalities of the
microvasculature and matrix have been reported in other congestive
cardiomyopathies, thereby suggesting that common pathophysiologic mechanisms may
lead to ventricular damage even when the initiating etiologic agent is different.
Preventive treatment or palliation of Chagas' cardiomyopathy and other congestive
cardiomyopathies may result from a better understanding of these secondary
pathogenetic events.
PMID- 25851576
TI - Myocardial inflammatory infiltrate in human chronic chagasic cardiomyopathy:
Immunohistochemical findings.
AB - Chagas' disease is the most common form of chronic myocarditis in the world. It
is characterized by a progressive chronic myocarditis that leads to cardiomegaly,
arrhythmias, cardiac failure, and thromboembolic phenomena. This communication
reports studies on the immunohistochemistry of chronic infiltrates in 30
endomyocardial biopsies and in contracting and specialized myocardium of
autopsies of four patients suffering from Chagas' cardiomyopathy. Expression of
the following antigens was studied: common leucocyte antigen (CLA-CD45R), L
26(CD20), CD68, kappa and lambda light chains and T-UCLH-1 (CD45RO), and MB-1.
Streptavidin-peroxidase and streptavidin-alkaline phosphatase with biotinylated
anti-mouse IgG were used as detection systems. Double immunostaining for the
simultaneous demonstration of T lymphocytes (CD45R0) and macrophages was
performed using both immunoenzymatic techniques consecutively. Expression of CD31
was detected for the demonstration of endothelial cells. In endomyocardial
biopsies, tissue forms of trypanosomes were not found. The percentage of fibrous
tissue was 24.1% +/- 12.8% (range 8.2%-49%). Eosinophils were scarce (1/high
power field), but associated with necrotic areas of the myocardium. Mast cells
were scarce or absent. They were always situated in fibrotic areas. The most
remarkable finding was the presence of infiltrates consisting of macrophages and
CLA-positive mononuclear cells. Twenty-six and one-half percent of them were T
lymphocytes, and 10.5% were B lymphocytes. Lymphocytic infiltration was
particularly associated with necrotic and degenerative myocardial lesions. Thirty
percent of the infiltrate was composed of macrophages (positive CD68 cells). The
remaining infiltrate was composed of mononuclear cells resembling macrophages and
CLA-negative mononuclear cells. Contacts between CD68-positive cells and T
lymphocytes were frequently found. CD31 antibodies clearly pointed out normal
endothelial cells, in either normal or damaged vessels. No isolated cells
positive for these antibodies were found within the mononuclear infiltrate. In
autopsied hearts, myocardial lesions consisted of a chronic inflammatory process
with fibrotic scars and extensive mononuclear infiltrates. No amastigote nests
were found. A statistically significant difference (p < 0.05) was obtained when
the percentage of fibrosis was compared in the specialized and contracting
myocardiums (51.6% +/- 18% vs. 43.4 % +/- 8%). Eosinophils were scarce in
infiltrates, reaching 5%, and they were associated with necrotic myocardium. Mast
cells also were scarce or absent in specialized and in contracting myocardium.
Almost all the lymphocytic population was T lymphocytes. Such infiltrates were
more prominent in the working myocardium (39%) and in the specialized cells of
the left branch of the His bundle than in the atrioventricular node and in the
right Hisian branch (34.4%). The 31% of mononuclear cells were CD68 positive,
thus corresponding to macrophages. Contacts among T lymphocytes and macrophages
were frequently observed. Although much that is concerned with Chagas'
cardiomyopathy is controversial, these may be the major ingredients for its
pathogenesis: the parasite or a part of it, lymphocytes and macrophages, and
fibrosis. Then a multifactorial or "combined theory" may be suggested to explain
the sequence of events that lead to the chronic stage of the disease.
PMID- 25851577
TI - Pathologic substrates for arrhythmogenesis in chronic chagasic cardiopathy.
AB - Here are described the results of a histopathological study on 12 autopsy hearts
of subjects deceased secondary to chronic chagasic cardiopathy in order to
clarify the nature and the pathogenetic mechanism of its arrhythmogenic
potential. The arrhythmogenic hazards of chagasic cardiomyopathy are mainly due
to the striking disruptive fibrotic changes with ensuing electrical instability
of the ventricular myocardium. Lesions of the conduction system, focal
epiperineuritis, and an inconstant and questionable "neuronal depletion" of the
cardiac plexuses in the disease play a concomitant role.
PMID- 25851578
TI - Cardiac extrinsic neuropathy: Lesions of the mediastinal paraganglia in chronic
chagasic cardiomyopathy.
AB - The pathology of cardiac innervation, both intrinsic and external to the heart
(mediastinal paraganglia included), is scarcely known, yet it can be critical to
life-threatening disorders in cardiac performance or to reflexes discharging
outside the heart, or both. This article focuses on such a fundamental and ill
understood subject through an anatomoclinical outlook of mediastinal paraganglia
lesions in the setting of sudden death in chronic chagasic cardiomyopathy.
PMID- 25851579
TI - Neuropathology of chronic chagasic cardiopathy: A diagnostic reassessment.
AB - Intrinsic innervation changes in chronic chagasic cardiopathy long have been
regarded as pathognomonic to the disease clinicopathologically and acritically
ascribed to incurable "neuronal depletion." This allegedly diffuse, frequent, and
devastating damage to parasympathetic cardiac ganglia was absent in the seven
cases we examined and was not demonstrated by reliable neuropathologic diagnosis
in former studies from the literature, where the evidence of Terplan nodules, the
very hallmark of autonomic neuronal loss, had been lamentably disregarded. Thus,
dysautonomic manifestations in chronic chagasic cardiopathy should be attributed
to the frequent and widespread finding of neuritic involvement in the severe
(auto-) immune fibrosing myocarditis peculiar to the disease.
PMID- 25851580
TI - Uptake of aromatic compounds by DNA: Toward the environmental application of DNA
for cleaning water.
AB - HYPOTHESIS: Although the interaction of DNA with various types of intercalating
chemicals, such as planar polycyclic aromatic compounds, has been extensively
investigated over the past several decades, little is known about the
relationship between the structure of a DNA binder and its affinity for DNA. The
use of DNA as an adsorbent for environmental cleaning purposes requires
information on its affinity for organic chemicals with different structures.
EXPERIMENT: In the present study we investigated the binding of DNA to aromatic
chemicals with various structures and charges by three methods: binding of
organic chemicals to DNA followed by removal by precipitation with cationic
nanoparticles (1) or a cationic surfactant (2), and absorption of organic
chemicals by a DNA hydrogel (3). FINDINGS: The results showed that, for most
neutral organic chemicals, the hydrophobicity of the organic molecule is the main
driving force for efficient binding to DNA. The double-helicity of DNA
contributed to stronger binding to most of the compounds. The efficiency of the
uptake of organic chemicals increased substantially when a hydrophobic cationic
surfactant was used for DNA-complex condensation and removal. The potential
environmental application of DNA as an adsorbent for the removal of aromatic
organic pollutants from water is discussed.
PMID- 25851581
TI - The fate of silica based Stober particles soaked into growth media (RPMI and
M254): A DLS and zeta-potential study.
AB - Understanding the mechanisms involved in the interaction of biological systems
with inorganic materials is of great importance and interest in both fundamental
and applied disciplines in several different fields such as astrobiology,
ecology, biology, biotechnology, engineering, and medicine. In this context, this
paper investigates the interaction of biomacromolecules with submicrometric
silica gel particles (NP) obtained through the Stober method. Surprisingly,
particles size reduction is observed after their dispersion into two different
reconstituted growth media (RPMI and M254). This effect was related to the nature
of the Stober particles and the mechanism of their formation. The experimental
results can be explained arguing that a biomacromolecule corona rapidly forms on
NP incubated in both RPMI and M254 growth media. The results suggest that
hydrolytic attack at incompletely condensed internal surface valence sites as
well as interactions between NPs surface and the components of the growth media
reverse the aggregation process, giving smaller disaggregated particles
surrounded by a biomacromolecule corona. Moreover it was assessed that, at longer
incubation time, the particles slightly grow probably due to interlocking of
biomacromolecules in the corona. Furthermore, experimental results confirm that
formation of this corona is a competitive and dynamic process. The present paper
shows that the described effects (as size changes) are strongly dependent on the
nature of the growth medium.
PMID- 25851582
TI - RGD-modified pH-sensitive liposomes for docetaxel tumor targeting.
AB - Phosphatidylethanolamine-based pH-sensitive liposomes of various compositions
have been described as efficient systems for delivery of therapeutic molecules
into tumor cells. The aim of this work was to develop a drug delivery system
based on pH-sensitive liposomes (PLPs) that were modified with arginine-glycine
aspartic acid (RGD) peptide to enhance the effectiveness of docetaxel treatment.
Docetaxel/coumarin-6 loaded PLPs were prepared by the thin-film dispersion method
and characterized in detail, including by particle size, polydispersity, zeta
potential and drug encapsulation efficiency. In vitro studies using MCF-7,
HepG2and A549 cells were employed to investigate cytotoxicity and cellular uptake
of the drug solution or docetaxel/coumarin-6 loaded PLPs. The accumulation of 7
nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled liposomes in vivo was studied
through tumor section imaging of xenograft mouse models of MCF-7 24h after
intravenous administration. The particle size of the non-coated or RGD modified
PLPs ranged between 146 and 129nm. Drug release in vitro was modestly prolonged
and had good pH sensitivity. In the in vitro study, RGD-coated PLPs showed higher
cytotoxicity and cellular uptake relative to non-coated ones. The results of the
in vivo study showed that RGD-coated PLPs had higher fluorescence, which
suggested a more efficient accumulation than normal PLPs in tumors. In
conclusion, these results confirmed RGD-modified PLPs as a potential drug
delivery system to achieve controlled release and tumor targeting.
PMID- 25851583
TI - High-Intensity Interval Exercise and Postprandial Triacylglycerol.
AB - This review examined if high-intensity interval exercise (HIIE) reduces
postprandial triacylglycerol (TAG) levels. Fifteen studies were identified, in
which the effect of interval exercise conducted at an intensity of >65% of
maximal oxygen uptake was evaluated on postprandial TAG levels. Analysis was
divided between studies that included supramaximal exercise and those that
included submaximal interval exercise. Ten studies examined the effect of a
single session of low-volume HIIE including supramaximal sprints on postprandial
TAG. Seven of these studies noted reductions in the postprandial total TAG area
under the curve the morning after exercise of between ~10 and 21% compared with
rest, but three investigations found no significant difference in TAG levels.
Variations in the HIIE protocol used, inter-individual variation or insufficient
time post-exercise for an increase in lipoprotein lipase activity are proposed
reasons for the divergent results among studies. Five studies examined the effect
of high-volume submaximal interval exercise on postprandial TAG. Four of these
studies were characterised by high exercise energy expenditure and effectively
attenuated total postprandial TAG levels by ~15-30%, but one study with a lower
energy expenditure found no effect on TAG. The evidence suggests that
supramaximal HIIE can induce large reductions in postprandial TAG levels but
findings are inconsistent. Submaximal interval exercise offers no TAG metabolic
or time advantage over continuous aerobic exercise but could be appealing in
nature to some individuals. Future research should examine if submaximal interval
exercise can reduce TAG levels in line with more realistic and achievable
exercise durations of 30 min per day.
PMID- 25851585
TI - Antepartum use of Epi-No birth trainer for preventing perineal trauma: systematic
review.
AB - INTRODUCTION AND HYPOTHESIS: In this systematic review we aimed to assess if the
Epi-No birth trainer used during antepartum could prevent perineal trauma in
nulliparous women. METHODS: We searched CENTRAL, MEDLINE, EMBASE, Scielo, and
Conference abstracts, looking for randomized controlled studies (RCT). High
heterogeneity (i(2) > 50 %) was corrected with random models. All studies were
analyzed according to their quality and risk of bias. Nulliparous women or women
whose previous pregnancy ended before 21 weeks' gestation were included and the
main outcome measures were: episiotomy rates, perineal tears, severe (3rd/4th)
perineal tears, and intact perineum. RESULTS: Five studies were included (1,369
participants) for systematic review and two of them (932 participants) were
eligible for meta-analysis. Epi-No did not reduce episiotomy rates (RR 0.92
[95%CI 0.75-1.13], n = 710, p =0.44; two studies; fixed model) and second stage
of labor (MD -12.50 [95%CI -29.62, -4.62], n = 162, p = 0.54; one study; fixed
model), and did not increase intact perineum (RR 1.15 [95 % CI 0.81-1.64], n =
705, p = 0.43; two studies; random model). No influence of Epi-No on reducing all
perineal tears (RR 0.99 [95%CI 0.84-1.17], n = 705, p = 0.93, two studies; fixed
model) or severe (3rd/4th) perineal tears (RR 1.31 [95%CI 0.72-2.37], n = 705, p
= 0.38, two studies; fixed model). Mean birthweight of the Epi-No group was
higher than that of the control group in both studies, with no statistical
significance. CONCLUSION: Epi-No birth trainer is a device that did not reduce
episiotomy rates and had no influence on reducing perineal tears.
PMID- 25851586
TI - Midterm results of robot-assisted sacrocolpopexy.
AB - INTRODUCTION AND HYPOTHESIS: Robotic assistance simplifies laparoscopic
procedures. We hypothesize that robot-assisted sacrocolpopexy is a rapid and safe
procedure with satisfying short-term and midterm functional results. METHODS:
After informed consent, we enrolled 101 consecutive patients undergoing
sacrocolpopexy at Alfried Krupp Hospital, Essen, Germany. After a median follow
up of 22 months, we assessed midterm functional results as the primary endpoint.
Secondary endpoints included surgical duration, blood loss, intraoperative
complications, and postoperative complications. We described frequencies as
counts (percent) and continuous data as median [interquartile range (Q1-Q3)] or
mean [standard deviation (SD)], as appropriate. RESULTS: We enrolled 101
patients. The mean age was 69 years (SD 11); 75 women (74.3 %) had undergone
previous abdominal surgery. Among the patients, 95 (94.1 %) presented with
anterior vaginal wall prolapse Baden-Walker grade 2-3, 74 (73.3 %) vaginal vault
prolapse, and 9 (8.9 %) concomitant rectocele. Fifty (50 %) patients underwent a
modified Burch procedure in addition to sacrocolpopexy. The median surgical
duration was 96 min (Q1-Q3 83-130). There were six (5.9 %) minor intraoperative
complications but no conversions to open surgery. Postoperatively, we registered
five (4.9 %) Clavien-Dindo grade I complications, three (3.0 %) grade II
complications, and one (1.0 %) grade III complication. After a median follow-up
of 22 months (Q1-Q3 12-49), the patients reported significant decreased impact of
pelvic organ prolapse (POP) on quality of life as well as bother resulting from
POP symptoms. The overall success rate, defined as none or minor impact of POP on
quality of life, was 75 %. CONCLUSIONS: In this single-surgeon study, robot
assisted sacrocolpopexy was a safe and rapidly performed procedure that achieved
good medium-term functional results.
PMID- 25851584
TI - What are the Differences in Injury Proportions Between Different Populations of
Runners? A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Many runners suffer from injuries. No information on high-risk
populations is available so far though. OBJECTIVES: The aims of this study were
to systematically review injury proportions in different populations of runners
and to compare injury locations between these populations. DATA SOURCES: An
electronic search with no date restrictions was conducted up to February 2014 in
the PubMed, Embase, SPORTDiscus and Web of Science databases. The search was
limited to original articles written in English. The reference lists of the
included articles were checked for potentially relevant studies. STUDY
ELIGIBILITY CRITERIA: Studies were eligible when the proportion of running
injuries was reported and the participants belonged to one or more homogeneous
populations of runners that were clearly described. Study selection was conducted
by two independent reviewers, and disagreements were resolved in a consensus
meeting. STUDY APPRAISAL AND SYNTHESIS METHODS: Details of the study design,
population of runners, sample size, injury definition, method of injury
assessment, number of injuries and injury locations were extracted from the
articles. The risk of bias was assessed with a scale consisting of eight items,
which was specifically developed for studies focusing on musculoskeletal
complaints. RESULTS: A total of 86 articles were included in this review. Where
possible, injury proportions were pooled for each identified population of
runners, using a random-effects model. Injury proportions were affected by injury
definitions and durations of follow-up. Large differences between populations
existed. The number of medical-attention injuries during an event was small for
most populations of runners, except for ultra-marathon runners, in which the
pooled estimate was 65.6%. Time-loss injury proportions between different
populations of runners ranged from 3.2% in cross-country runners to 84.9% in
novice runners. Overall, the proportions were highest among short-distance track
runners and ultra-marathon runners. LIMITATIONS: The results were pooled by
stratification of studies according to the population, injury definition and
follow-up/recall period; however, heterogeneity was high. CONCLUSIONS: Large
differences in injury proportions between different populations of runners
existed. Injury proportions were affected by the duration of follow-up. A U
shaped pattern between the running distance and the time-loss injury proportion
seemed to exist. Future prospective studies of injury surveillance are highly
recommended to take running exposure and censoring into account.
PMID- 25851588
TI - Cardiac resynchronisation therapy in 2015: keeping up with the pace.
AB - Despite improved understanding of the pathophysiology of heart failure (HF) and
availability of better medical therapies, HF continues to grow as a cause of
morbidity and mortality in Australia and worldwide. Over the past decade, cardiac
resynchronisation therapy (CRT), or biventricular pacing, has been embraced as a
powerful weapon against this growing epidemic. However, much has changed in our
understanding of dyssynchrony in HF, and this has led to a change in guidelines
to ensure more appropriate selection of CRT candidates to improve the 'non
response' rate. More data have also emerged about the use of CRT in atrial
fibrillation and in pacemaker-dependent patients. There has also been a growing
focus on multimodality imaging to guide patient selection and lead positioning.
Exciting new lead technologies are also emerging, with the potential to improve
CRT outcomes further.
PMID- 25851589
TI - Impacts of the Minamata convention on mercury emissions and global deposition
from coal-fired power generation in Asia.
AB - We explore implications of the United Nations Minamata Convention on Mercury for
emissions from Asian coal-fired power generation, and resulting changes to
deposition worldwide by 2050. We use engineering analysis, document analysis, and
interviews to construct plausible technology scenarios consistent with the
Convention. We translate these scenarios into emissions projections for 2050, and
use the GEOS-Chem model to calculate global mercury deposition. Where technology
requirements in the Convention are flexibly defined, under a global energy and
development scenario that relies heavily on coal, we project ~90 and 150 Mg.y(-1)
of avoided power sector emissions for China and India, respectively, in 2050,
compared to a scenario in which only current technologies are used. Benefits of
this avoided emissions growth are primarily captured regionally, with projected
changes in annual average gross deposition over China and India ~2 and 13 MUg.m(
2) lower, respectively, than the current technology case. Stricter, but
technologically feasible, mercury control requirements in both countries could
lead to a combined additional 170 Mg.y(-1) avoided emissions. Assuming only
current technologies but a global transition away from coal avoids 6% and 36%
more emissions than this strict technology scenario under heavy coal use for
China and India, respectively.
PMID- 25851587
TI - A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic
lineage.
AB - Short- and long-scales intra- and inter-chromosomal interactions are linked to
gene transcription, but the molecular events underlying these structures and how
they affect cell fate decision during embryonic development are poorly
understood. One of the first embryonic cell fate decisions (that is, mesendoderm
determination) is driven by the POU factor OCT4, acting in concert with the high
mobility group genes Sox-2 and Sox-17. Here we report a chromatin-remodelling
mechanism and enhancer function that mediate cell fate switching. OCT4 alters the
higher-order chromatin structure at both Sox-2 and Sox-17 loci. OCT4 titrates out
cohesin and switches the Sox-17 enhancer from a locked (within an inter
chromosomal Sox-2 enhancer/CCCTC-binding factor CTCF/cohesin loop) to an active
(within an intra-chromosomal Sox-17 promoter/enhancer/cohesin loop) state. SALL4
concomitantly mobilizes the polycomb complexes at the Soxs loci. Thus, OCT4/SALL4
driven cohesin- and polycombs-mediated changes in higher-order chromatin
structure mediate instruction of early cell fate in embryonic cells.
PMID- 25851590
TI - Massilia eurypsychrophila sp. nov. a facultatively psychrophilic bacteria
isolated from ice core.
AB - Strain B528-3(T), a Gram-stain-negative, rod-shaped, aerobic, facultatively
psychrophilic bacterium with polar flagella, was isolated from an ice core
drilled from Muztagh Glacier, Xinjiang, China. The novel isolate was classified
into the genus Massilia. The 16S rRNA gene sequence of the novel isolate shares a
pairwise similarity of less than 97% with those of all the type strains of the
genus Massilia. The major fatty acids of strain B528-3(T) were summed feature 3
(C16:1omega7c and/or iso-C15:0 2-OH) (57.31%), C16:0 (11.46%) and C18:1omega7c
(14.72%). The predominant isoprenoid quinone was Q-8. The DNA G + C content was
62.2 mol% (Tm). The major polar lipids of this bacterium were
phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. From
the genotypic and phenotypic data, it is evident that strain B528-3(T) represents
a novel species of the genus Massilia, for which the name Massilia
eurypsychrophila sp. nov. is proposed. The type strain is B528-3(T) ( = JCM
30074(T) = CGMCC 1.12828(T)).
PMID- 25851591
TI - Cecembia rubra sp. nov., a thermophilic bacterium isolated from a hot spring
sediment.
AB - A Gram-staining negative, rod-shaped bacterium, designated strain YIM 78110(T),
was isolated from a sediment sample collected from Hehua hot spring in Tengchong,
Yunnan province, south-west China. The taxonomic status of strain YIM 78110(T)
was confirmed by a polyphasic approach. 16S rRNA gene sequence analysis indicated
that strain YIM 78110(T) belongs to the genus Cecembia, displaying 96.8% and
94.7% sequence similarity with the two most closely related type strains,
Cecembia calidifontis RQ-33(T) and Cecembia lonarensis LW9T, respectively. The
low value of DNA-DNA hybridization (52.3 +/- 2.3%) between strain YIM 78110(T)
and its closest neighbour, Cecembia calidifontis RQ-33(T), indicated that this
new isolate represented a different genomic species in the genus Cecembia. The
temperature for growth ranged from 30 to 50 degrees C. The pH for growth ranged
from pH 4.0 to 10.0, with NaCl tolerance of 0.5-6.0% (w/v). The predominant
menaquinone of strain YIM 78110(T) was MK-7 and the major polar lipid was
phosphatidylethanolamine. The major fatty acids were iso-C15:0 and C15:0. The DNA
G+C content was 47.1 mol%. On the basis of physiological, biochemical and
phylogenetic analyses, it is proposed that strain YIM 78110(T) represents a novel
species of the genus Cecembia, for which the name Cecembia rubra sp. nov. is
proposed. The type strain is YIM 78110(T) ( = CCTCC AB2013287(T) = DSM 28057(T)).
PMID- 25851592
TI - Escherichia marmotae sp. nov., isolated from faeces of Marmota himalayana.
AB - The taxonomic position of a group of seven closely related lactose-negative
enterobacterial strains, which were isolated from fresh faecal samples of Marmota
himalayana collected from the Qinghai-Tibetan plateau, China, was determined by
using a polyphasic approach. Cells were Gram-reaction-negative, non-sporulating,
non-motile, short rods (0.5-1 * 1-2.5 MUm). By 16S rRNA gene sequences, the
representative strain, HT073016(T), showed highest similarity values with
Escherichia fergusonii ATCC 35469(T) at 99.3%, Escherichia coli ATCC 11775(T) at
99.2%, Escherichia albertii LMG 20976(T) at 98.9%, Escherichia hermannii CIP
103176(T) at 98.4%, and Escherichia vulneris ATCC 33821(T) at 97.7%. Phylogenetic
analysis based on the 16S rRNA gene sequences showed that the seven strains
formed a monophyletic group with five other species of the genus Escherichia.
Digital DNA-DNA hybridization studies between strain HT073016(T) and five other
species of the genus Escherichia showed that it shared less than 70% DNA-DNA
relatedness with all known species of the genus Escherichia, supporting the novel
species status of the strain. The DNA G+C content of strain HT073016(T) was 53.8
mol%. On the basis of phenotypic and phylogenetic characteristics, strain
HT073016(T) and the six other HT073016(T)-like strains were clearly distinct from
the type strains of other recognized species of the genus Escherichia and
represent a novel species of the genus Escherichia, for which the name
Escherichia marmotae sp. nov. is proposed, with HT073016(T) ( = CGMCC 1.12862(T)
= DSM 28771(T)) as the type strain.
PMID- 25851593
TI - Pseudomonas endophytica sp. nov., isolated from stem tissue of Solanum tuberosum
L. in Spain.
AB - A bacterial strain named BSTT44(T) was isolated in the course of a study of
endophytic bacteria occurring in stems and roots of potato growing in a soil from
Salamanca, Spain. The 16S rRNA gene sequence had 99.7% identity with respect to
that of its closest relative, Pseudomonas psychrophila E-3T, and the next most
closely related type strains were those of Pseudomonas fragi, with 99.6%
similarity, Pseudomonas deceptionensis, with 99.2% similarity, and Pseudomonas
lundensis, with 99.0% similarity; these results indicate that BSTT44(T) should be
classified within the genus Pseudomonas. Analysis of the housekeeping genes rpoB,
rpoD and gyrB confirmed its phylogenetic affiliation and showed identities lower
than 92% in all cases with respect to the above-mentioned closest relatives.
Cells of the strain bore one polar-subpolar flagellum. The respiratory quinone
was Q-9.The major fatty acids were C16:0, C18:1omega7c and summed feature 3
(C16:1omega7c and/or C16:1omega6c). The strain was oxidase-, catalase- and urease
positive and the arginine dihydrolase system was present, but tests for nitrate
reduction, beta-galactosidase production and aesculin hydrolysis were negative.
It could grow at 35 degrees C and at pH 5-9.The DNA G+C content was 60.2 mol%.
DNA-DNA hybridization results showed less than 48% relatedness with respect to
the type strains of the four most closely related species. Therefore, the
combined results of genotypic, phenotypic and chemotaxonomic analyses support the
classification of strain BSTT44 into a novel species of the genus Pseudomonas,
for which the name Pseudomonas endophytica sp. nov. is proposed. The type strain
is BSTT44(T) ( = LMG 28456(T) = CECT 8691(T)).
PMID- 25851595
TI - Polymer-Derived Ceramic Functionalized MoS2 Composite Paper as a Stable Lithium
Ion Battery Electrode.
AB - A facile process is demonstrated for the synthesis of layered SiCN-MoS2 structure
via pyrolysis of polysilazane functionalized MoS2 flakes. The layered morphology
and polymer to ceramic transformation on MoS2 surfaces was confirmed by use of
electron microscopy and spectroscopic techniques. Tested as thick film electrode
in a Li-ion battery half-cell, SiCN-MoS2 showed the classical three-stage
reaction with improved cycling stability and capacity retention than neat MoS2.
Contribution of conversion reaction of Li/MoS2 system on overall capacity was
marginally affected by the presence of SiCN while Li-irreversibility arising from
electrolyte decomposition was greatly suppressed. This is understood as one of
the reasons for decreased first cycle loss and increased capacity retention. SiCN
MoS2 in the form of self-supporting paper electrode (at 6 mg.cm(-2)) exhibited
even better performance, regaining initial charge capacity of approximately 530
mAh.g(-1) when the current density returned to 100 mA.g(-1) after continuous
cycling at 2400 mA.g(-1) (192 mAh.g(-1)). MoS2 cycled electrode showed mud-cracks
and film delamination whereas SiCN-MoS2 electrodes were intact and covered with a
uniform solid electrolyte interphase coating. Taken together, our results suggest
that molecular level interfacing with precursor-derived SiCN is an effective
strategy for suppressing the metal-sulfide/electrolyte degradation reaction at
low discharge potentials.
PMID- 25851594
TI - Drug survival and causes of discontinuation of the first anti-TNF in ankylosing
spondylitis compared with rheumatoid arthritis: analysis from BIOBADABRASIL.
AB - Treatment survival with biological therapy may be influenced by many factors, and
it seems to be different among various rheumatic diseases and biological agents.
The goal of the study was to compare the drug survival and the causes of
discontinuation of anti-tumoral necrosis factor (anti-TNF) therapy in ankylosing
spondylitis (AS) with rheumatoid arthritis (RA). Study participants were a cohort
from the Brazilian Registry of Biological Therapies in Rheumatic Diseases
(BIOBADABRASIL) between 2008 and 2012. The observation time was up to 4 years
following the introduction of the first treatment. Gender, age, disease duration,
disease activity, comorbidities, and concomitant therapies were assessed. A total
of 1303 patients were included: 372 had AS and 931 had RA in which 38.7 % (n =
504) used infliximab (IFX), 34.9 % (n = 455) used adalimumab (ADA), and 26.4 % (n
= 344) used etanercept (ETA). The anti-TNF drug survival of patients with AS was
63.08 months (confidence interval (CI) 60.24, 65.92) and patients with RA was
47.5 months (CI 45.65, 49.36). It was significant higher in AS (log-rank; p <=
0.001). Patients with RA discontinued anti-TNF more than patients with AS when
adjusted to gender and corticosteroid. The adjHR (95 % CI) was 1.6 (1.14, 2.31).
Female patients who were also corticosteroid users, but not of advanced age, have
shown lower survival for both diseases (log-rank, p <= 0.001). The
discontinuation rate of IFX, but not of ADA or ETA, was significantly higher in
RA than in SA; HR (95 % CI) was 2.49 (1.46, 4.24). The main causes of
discontinuation were ineffectiveness and adverse event in both diseases. AS
patients have better drug survival adjusted to gender, age, and corticosteroid.
This results appear to be related to the disease mechanism.
PMID- 25851597
TI - Early Activation of Metalloproteinases after Experimental Myocardial Infarction
Occurs in Infarct and Non-infarct Zones.
AB - The collagen matrix of the heart forms a network linking muscle fibers, muscle
bundles, and intramyocardial blood vessels. Collagen turnover in the heart is
normally a dynamic process that involves both collagen synthesis and degradation.
Collagen breakdown generally involves its chemical digestion by matrix
metalloproteinases (MMPs) which are activated in tissue repair, wound healing,
and myocardial ischemia. We studied activation of MMPs by zymography in infarct
(anterolateral wall) and non-infarct (septum) zones of rat hearts following
coranary artery ligation, as well as in sham operated rats. Rats were sacrificed
at 30 minutes, 1 hour, 2 hours, 4 hours, and 24 hours post infarction (six hearts
for each time period). MMP activity was detected at different molecular weights,
with bands at 54 kDa (MMP-1), 62 kDa (MMP-2), and 92 kDa (MMP-9) being the most
prominent. MMP activities were indexed by densitometer optical reading. Activity
was detected as early as 1 hour post infarct in the MI and remote zones at the 54
kDa (MMP-1) ( p < 0.01) and 62 kDa bands (MMP-2) ( p < 0.001), and at 2 hours
post infarct in the infarct zone only at 92 kDa (MMP-9) ( p < 0.05). MMPs are
activated early after infarction both in the infarct and importantly, non-infarct
zones. This may contribute to collagen breakdown, infarct expansion, and left
ventricular remodeling, known to occur early after infarction in experimental and
clinical settings.
PMID- 25851596
TI - Identification of Commonly Dysregulated Genes in Non-small-cell Lung Cancer by
Integrated Analysis of Microarray Data and qRT-PCR Validation.
AB - BACKGROUND: Non-small-cell lung cancer (NSCLC), the most common lung cancer,
leads to the largest number of cancer-related deaths worldwide. There are many
studies to identify the differentially expressed genes (DEGs) between NSCLC and
normal control (NC) tissues by means of microarray technology. Because of the
inconsistency of the microarray data sets, we performed an integrated analysis to
identify DEGs and analyzed their biological function. METHODS AND RESULTS: We
combined 15 microarray data sets and identified 1063 DEGs between NSCLC and NC
tissues; in addition, we found that the DEGs were enriched in regulation of cell
proliferation process and focal adhesion signaling pathway. The protein-protein
interaction network analysis for the top 20 significantly DEGs revealed that
CAV1, COL1A1, and ADRB2 were the significant hub proteins. Finally, we employed
qRT-PCR to validate the meta-analysis approach by determining the expression of
the top 10 most significantly DEGs and found that the expression of these genes
were significantly different between tumor and NC tissues, in accordance with the
results of meta-analysis. CONCLUSION: qRT-PCR results indicated that the meta
analysis approach in our study was acceptable. Our data suggested that some of
the DEGs, including MMP12, COL11A1, THBS2, FAP, and CAV1, may participate in the
pathology of NSCLC and could be applied as potential markers or therapeutic
targets for NSCLC.
PMID- 25851598
TI - Causes of isolated aortic insufficiency in an urban population in the 1990s a
review of 56 surgical pathology cases.
AB - Until recently, the cause of isolated aortic insufficiency (AI) was usually
thought to be inflammatory or rheumatic in most cases. However, at our
institution we have noted a high prevalence of myxomatous degeneration (MD) in
aortic valves removed for AI. In this study we report anatomic observations on
valves from 56 consecutive patients with isolated AI undergoing aortic valve
replacement surgery. Fifty-six consecutive aortic valves removed at our
institution from 1994 to 1996 for isolated AI and/or aortic aneurysm were
reviewed. Anatomic features were compared with clinical history and
echocardiographic data. The anatomic results were also compared to 22 age-matched
control aortic valves obtained at autopsy. In 13/56 cases (23%), a specific
valvular cause of AI was determined (infectious endocarditis, seven cases;
chronic rheumatic disease, four cases; congenital bicuspid valve, two cases). Of
the remaining (idiopathic) 43 cases, 18 (42%) had severe isolated MD defined as
>50% expansion of the spongiosa and disruption of the fibrosa by the deposition
of acid mucopolysaccharides in the absence of severe calcification, fibrosis, or
other pathologic findings. Only 1/22 aortic valves from the autopsy controls had
severe MD. Eighteen of the 56 patients also had a clinical history of aortic
dilatation/aneurysm of which 12 were confirmed to be dilated by echocardiographic
criteria. Of these 12, five (42%) had MD of the aortic valve only, three (25%)
had both MD and cystic medial degeneration (CMD) of the aorta, two (17%) had CMD
of the aorta only, and two (17%) had no specific diagnosis. Isolated MD of the
aortic valve is the most common cause of isolated AI in our patient population.
Furthermore, in a subset of non-Marfan's patients with both AI and dilatation of
the aortic root/aortic aneurysm the incidence of MD is even higher (67%). These
results suggest that there is overlap between MD and CMD in non-Marfan's patients
and that both entities may be part of a spectrum of a generalized connective
tissue disorder.
PMID- 25851599
TI - The acute effects of outdoor temperature on blood pressure in a panel of elderly
hypertensive patients.
AB - Higher level of blood pressure (BP) in winter than in summer has been observed,
but the association between temperature and BP and its potential modifiers with
adjustment of individual confounders and time trends was rarely explored. We
aimed to investigate the association between outdoor temperature and BP and its
potential modification factors in a longitudinal panel study in Shanghai, China.
From January 2011 to December 2012, we scheduled 54 follow-ups for BP
measurements per subject via home visit every other week for 50 elderly
hypertensive patients. We applied linear mixed-effect models to analyze the
association between temperature and BP after controlling for individual
characteristics, antihypertensive medication, comorbidities, and time trends. We
evaluated the potential effect modifiers by stratification analyses. For a 1
degrees C decrease in the average temperature on concurrent day and previous day,
systolic BP increased by 0.19 mmHg (95 % confidence interval = 0.06, 0.31) and
diastolic BP increased by 0.12 mmHg (95 % confidence interval = 0.03, 0.21). The
effect of temperature on BP was stronger among those with older age, female sex,
low socioeconomic status, and obese physique. The effect was weak and even null
for those taking the angiotensin receptor blockers, angiotensin-converting enzyme
inhibitor, or its combination with calcium antagonists. Further, the effect was
almost restricted within those having chronic comorbidities. Our results
demonstrated that an acute decrease in outdoor temperature was significantly
associated with a rise in BP among elderly hypertensive patients, in Shanghai,
China. Individual characteristics, antihypertensive medications, and
comorbidities may modify this effect.
PMID- 25851600
TI - Casein kinase 1 controls the activation threshold of an alpha-arrestin by
multisite phosphorylation of the interdomain hinge.
AB - alpha-Arrestins play a key role as trafficking adaptors in both yeast and
mammals. The yeast Rim8/Art9 alpha-arrestin mediates the recruitment of endosomal
sorting complex required for transport (ESCRT) to the seven-transmembrane protein
Rim21 in the ambient pH signaling RIM pathway. ESCRT is believed to function as a
signaling platform that enables the proteolytic activation of the Rim101
transcription factor upon external alkalization. Here we provide evidence that
the pH signal promotes the stable association of Rim8 with Rim21 at the plasma
membrane. We show that Rim8 is phosphorylated in a pH-independent but Rim21
dependent manner by the plasma membrane-associated casein kinase 1 (CK1). We
further show that this process involves a cascade of phosphorylation events
within the hinge region connecting the arrestin domains. Strikingly, loss of
casein kinase 1 activity causes constitutive activation of the RIM pathway, and,
accordingly, pH signaling is activated in a phosphodeficient Rim8 mutant and
impaired in the corresponding phosphomimetic mutant. Our results indicate that
Rim8 phosphorylation prevents its accumulation at the plasma membrane at acidic
pH and thereby inhibits RIM signaling. These findings support a model in which
CK1-mediated phosphorylation of Rim8 contributes to setting a signaling threshold
required to inhibit the RIM pathway at acidic pH.
PMID- 25851601
TI - The RhoGEF DOCK10 is essential for dendritic spine morphogenesis.
AB - By regulating actin cytoskeleton dynamics, Rho GTPases and their activators
RhoGEFs are implicated in various aspects of neuronal differentiation, including
dendritogenesis and synaptogenesis. Purkinje cells (PCs) of the cerebellum, by
developing spectacular dendrites covered with spines, represent an attractive
model system in which to decipher the molecular signaling underlying these
processes. To identify novel regulators of dendritic spine morphogenesis among
members of the poorly characterized DOCK family of RhoGEFs, we performed gene
expression profiling of fluorescence-activated cell sorting (FACS)-purified
murine PCs at various stages of their postnatal differentiation. We found a
strong increase in the expression of the Cdc42-specific GEF DOCK10. Depleting
DOCK10 in organotypic cerebellar cultures resulted in dramatic dendritic spine
defects in PCs. Accordingly, in mouse hippocampal neurons, depletion of DOCK10 or
expression of a DOCK10 GEF-dead mutant led to a strong decrease in spine density
and size. Conversely, overexpression of DOCK10 led to increased spine formation.
We show that DOCK10 function in spinogenesis is mediated mainly by Cdc42 and its
downstream effectors N-WASP and PAK3, although DOCK10 is also able to activate
Rac1. Our global approach thus identifies an unprecedented function for DOCK10 as
a novel regulator of dendritic spine morphogenesis via a Cdc42-mediated pathway.
PMID- 25851602
TI - Asymmetric formation of coated pits on dorsal and ventral surfaces at the leading
edges of motile cells and on protrusions of immobile cells.
AB - Clathrin/AP2-coated vesicles are the principal endocytic carriers originating at
the plasma membrane. In the experiments reported here, we used spinning-disk
confocal and lattice light-sheet microscopy to study the assembly dynamics of
coated pits on the dorsal and ventral membranes of migrating U373 glioblastoma
cells stably expressing AP2 tagged with enhanced green fluorescence (AP2-EGFP)
and on lateral protrusions from immobile SUM159 breast carcinoma cells, gene
edited to express AP2-EGFP. On U373 cells, coated pits initiated on the dorsal
membrane at the front of the lamellipodium and at the approximate boundary
between the lamellipodium and lamella and continued to grow as they were swept
back toward the cell body; coated pits were absent from the corresponding ventral
membrane. We observed a similar dorsal/ventral asymmetry on membrane protrusions
from SUM159 cells. Stationary coated pits formed and budded on the remainder of
the dorsal and ventral surfaces of both types of cells. These observations
support a previously proposed model that invokes net membrane deposition at the
leading edge due to an imbalance between the endocytic and exocytic membrane flow
at the front of a migrating cell.
PMID- 25851603
TI - Sorting nexin 27 regulates basal and stimulated brush border trafficking of NHE3.
AB - Sorting nexin 27 (SNX27) contains a PDZ domain that is phylogenetically related
to the PDZ domains of the NHERF proteins. Studies on nonepithelial cells have
shown that this protein is located in endosomes, where it regulates trafficking
of cargo proteins in a PDZ domain-dependent manner. However, the role of SNX27 in
trafficking of cargo proteins in epithelial cells has not been adequately
explored. Here we show that SNX27 directly interacts with NHE3 (C-terminus)
primarily through the SNX27 PDZ domain. A combination of knockdown and
reconstitution experiments with wild type and a PDZ domain mutant (GYGF -> GAGA)
of SNX27 demonstrate that the PDZ domain of SNX27 is required to maintain basal
NHE3 activity and surface expression of NHE3 in polarized epithelial cells.
Biotinylation-based recycling and degradation studies in intestinal epithelial
cells show that SNX27 is required for the exocytosis (not endocytosis) of NHE3
from early endosome to plasma membrane. SNX27 is also required to regulate the
retention of NHE3 on the plasma membrane. The findings of the present study
extend our understanding of PDZ-mediated recycling of cargo proteins from
endosome to plasma membrane in epithelial cells.
PMID- 25851604
TI - The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not
rRNA modification are required for ribosome biogenesis.
AB - At the heart of the ribosome lie rRNAs, whose catalytic function in translation
is subtly modulated by posttranscriptional modifications. In the small ribosomal
subunit of budding yeast, on the 18S rRNA, two adjacent adenosines (A1781/A1782)
are N(6)-dimethylated by Dim1 near the decoding site, and one guanosine (G1575)
is N(7)-methylated by Bud23-Trm112 at a ridge between the P- and E-site tRNAs.
Here we establish human DIMT1L and WBSCR22-TRMT112 as the functional homologues
of yeast Dim1 and Bud23-Trm112. We report that these enzymes are required for
distinct pre-rRNA processing reactions leading to synthesis of 18S rRNA, and we
demonstrate that in human cells, as in budding yeast, ribosome biogenesis
requires the presence of the modification enzyme rather than its RNA-modifying
catalytic activity. We conclude that a quality control mechanism has been
conserved from yeast to human by which binding of a methyltransferase to nascent
pre-rRNAs is a prerequisite to processing, so that all cleaved RNAs are committed
to faithful modification. We further report that 18S rRNA dimethylation is
nuclear in human cells, in contrast to yeast, where it is cytoplasmic. Yeast and
human ribosome biogenesis thus have both conserved and distinctive features.
PMID- 25851605
TI - Cyclin-dependent kinase 5 acts as a critical determinant of AKT-dependent
proliferation and regulates differential gene expression by the androgen receptor
in prostate cancer cells.
AB - Contrary to cell cycle-associated cyclin-dependent kinases, CDK5 is best known
for its regulation of signaling processes in differentiated cells and its
destructive activation in Alzheimer's disease. Recently, CDK5 has been implicated
in a number of different cancers, but how it is able to stimulate cancer-related
signaling pathways remains enigmatic. Our goal was to study the cancer-promoting
mechanisms of CDK5 in prostate cancer. We observed that CDK5 is necessary for
proliferation of several prostate cancer cell lines. Correspondingly, there was
considerable growth promotion when CDK5 was overexpressed. When examining the
reasons for the altered proliferation effects, we observed that CDK5
phosphorylates S308 on the androgen receptor (AR), resulting in its stabilization
and differential expression of AR target genes including several growth-priming
transcription factors. However, the amplified cell growth was found to be
separated from AR signaling, further corroborated by CDK5-dependent proliferation
of AR null cells. Instead, we found that the key growth-promoting effect was due
to specific CDK5-mediated AKT activation. Down-regulation of CDK5 repressed AKT
phosphorylation by altering its intracellular localization, immediately followed
by prominent cell cycle inhibition. Taken together, these results suggest that
CDK5 acts as a crucial signaling hub in prostate cancer cells by controlling
androgen responses through AR, maintaining and accelerating cell proliferation
through AKT activation, and releasing cell cycle breaks.
PMID- 25851607
TI - Cognitive impairment and potential biological and psychological correlates of
neuropsychological performance in recently orchiectomized testicular cancer
patients.
AB - OBJECTIVE: The aim of this study was to determine the prevalence of cognitive
impairment (CI) in newly diagnosed and orchiectomized testicular cancer (TC)
patients prior to systemic treatment, and to explore biological and psychological
correlates. METHODS: Sixty-six TC patients were compared with 25 healthy men on
neuropsychological tests and a measure of cognitive complaints. CI status and a
global composite score (representing overall neuropsychological performance) were
calculated for each participant. Possible psychological (depression, anxiety,
stress, and post-traumatic stress symptoms) and biological (cortisol, IL-6, TNF
alpha, and CRP) correlates and predictors of patients' cognitive functioning were
explored. RESULTS: TC patients had lower scores on 6 out of 11 neuropsychological
outcomes (p < 0.01) in processing speed, attention, and working memory, verbal
learning and memory, and verbal fluency. Prevalence of CI among TC patients was
58%, significantly exceeding the frequency in healthy men (p < 0.01). Patients'
cortisol levels predicted overall neuropsychological performance (p = 0.04).
Cognitive complaints were associated with IL-6 (p = 0.02) and all psychological
distress measures (p < 0.001). CONCLUSIONS: The prevalence of CI in recently
orchiectomized TC patients was unexpectedly high with patients performing more
poorly than healthy controls on a majority of neuropsychological outcomes.
Cortisol is a potential predictor of neuropsychological performance in TC
patients prior to cytotoxic treatment.
PMID- 25851606
TI - Twitchin kinase interacts with MAPKAP kinase 2 in Caenorhabditis elegans striated
muscle.
AB - In Caenorhabditis elegans, twitchin is a giant polypeptide located in muscle A
bands. The protein kinase of twitchin is autoinhibited by 45 residues upstream
(NL) and 60 residues downstream (CRD) of the kinase catalytic core. Molecular
dynamics simulation on a twitchin fragment revealed that the NL is released by
pulling force. However, it is unclear how the CRD is removed. To identify
proteins that may remove the CRD, we performed a yeast two-hybrid screen using
twitchin kinase as bait. One interactor is MAK-1, C. elegans orthologue of MAPKAP
kinase 2. MAPKAP kinase 2 is phosphorylated and activated by p38 MAP kinase. We
demonstrate that the CRD of twitchin is important for binding to MAK-1. mak-1 is
expressed in nematode body wall muscle, and antibodies to MAK-1 localize between
and around Z-disk analogues and to the edge of A-bands. Whereas unc-22 mutants
are completely resistant, mak-1 mutants are partially resistant to nicotine. MAK
1 can phosphorylate twitchin NL-Kin-CRD in vitro. Genetic data suggest the
involvement of two other mak-1 paralogues and two orthologues of p38 MAP kinase.
These results suggest that MAK-1 is an activator of twitchin kinase and that the
p38 MAP kinase pathway may be involved in the regulation of twitchin.
PMID- 25851608
TI - Coping with burns: the role of coping self-efficacy in the recovery from
traumatic stress following burn injuries.
AB - We conducted a three-wave prospective study among patients with burns (N = 178)
to examine the prospective influence of coping self-efficacy (CSE) perceptions on
trajectories of posttraumatic stress symptoms in the first 12 months after burn
injuries. Using linear growth curve modeling, we corrected for demographics, the
number of surgeries during initial admittance, trait coping styles, and changing
levels of health-related quality of life. CSE during initial admission was by far
the strongest predictor of both initial PTSD symptoms and degree of symptom
change with higher CSE levels associated with lower initial symptoms and a
steeper decline of symptoms over time. Of the other variables only avoidant
coping was associated with higher initial symptom levels, and only emotional
expression associated with greater rate of recovery. Current findings suggest
that CSE plays a pivotal role in recovery from posttraumatic stress after a burn
injury, even when the role of burn-related impairments is taken into
consideration. Implications of findings are discussed.
PMID- 25851609
TI - Exercise habit formation in new gym members: a longitudinal study.
AB - Reasoned action approaches have primarily been applied to understand exercise
behaviour for the past three decades, yet emerging findings in unconscious and
Dual Process research show that behavior may also be predicted by automatic
processes such as habit. The purpose of this study was to: (1) investigate the
behavioral requirements for exercise habit formation, (2) how Dual Process
approach predicts behaviour, and (3) what predicts habit by testing a model
(Lally and Gardner in Health Psychol Rev 7:S137-S158, 2013). Participants (n =
111) were new gym members who completed surveys across 12 weeks. It was found
that exercising for at least four bouts per week for 6 weeks was the minimum
requirement to establish an exercise habit. Dual Process analysis using Linear
Mixed Models (LMM) revealed habit and intention to be parallel predictors of
exercise behavior in the trajectory analysis. Finally, the habit antecedent model
in LLM showed that consistency (beta = .21), low behavioral complexity (beta =
.19), environment (beta = .17) and affective judgments (beta = .13) all
significantly (p < .05) predicted changes in habit formation over time. Trainers
should keep exercises fun and simple for new clients and focus on consistency
which could lead to habit formation in nearly 6 weeks.
PMID- 25851610
TI - Affective associations and cognitive beliefs relate to individuals' decisions to
perform testicular or breast self-exams.
AB - Affective associations with behavioral practices play an important role in
individuals' uptake of a variety of health behaviors. Most work has looked at
individual behavioral practices with a direct impact on health; because screening
behaviors are conceptually distinct from such behaviors, it is important to
examine the interplay of affect and cognition in screening decision making. The
current research explored affective and cognitive predictors of testicular and
breast self-examination behavior. Young adult participants (N = 184) reported
cognitive beliefs and affective associations with testicular self-exam behavior
(male participants) and breast self-exam behavior (female participants) and
reported their own current screening behavior. In univariable models, affective
associations were related to screening behavior for both testicular self-exams
and breast self-exams. When examining affective associations and cognitive
beliefs as simultaneous predictors, affective associations (but not cognitive
beliefs) predicted testicular self-exams, and neither affective associations nor
cognitive beliefs were uniquely related to breast self-exams. Moreover, for
testicular self-exams, affective associations mediated the relation between
cognitive beliefs and screening behavior; no mediation was present for breast
self-exam behavior. These findings suggest three potential outcomes: first, that
greater consideration of affective associations in testicular self-exam screening
decisions may be warranted; second, that breast and testicular self-exams may
have different antecedents; and third, that incorporation of affective factors in
intervention design might have merit for increasing engagement in some cancer
screening behaviors.
PMID- 25851611
TI - Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative
stress during pig muscle maturation.
AB - The objective of this work was to study the postmortem evolution of potential
biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and oxidative stress
(total antioxidant activity, TAA; superoxide dismutase activity, SOD and catalase
activity, CAT) in the Longissimus dorsi muscle of entire male ((Large
White*Landrace)*Duroc) pigs subjected to different management treatments that may
promote stress, such as mixing unfamiliar animals at the farm and/or during
transport and lairage before slaughter. During the rearing period at the farm,
five animals were never mixed after the initial formation of the experimental
groups (unmixed group at the farm, UF), whereas 10 animals were subjected to a
common routine of being mixed with unfamiliar animals (mixed group at the farm,
MF). Furthermore, two different treatments were used during the transport and
lairage before slaughter: 10 pigs were not mixed (unmixed group during transport
and lairage, UTL), whereas five pigs were mixed with unfamiliar animals on the
lorry and during lairage (mixed group during transport and lairage, MTL). These
mixing treatments were then combined into three pre-slaughter treatments -
namely, UF-UTL, MF-UTL and MF-MTL. The results show that MF-UTL and MF-MTL
increased significantly the muscle antioxidant defense (TAA, SOD and CAT) at
short postmortem times (4 and 8 h; P<0.001), followed by an earlier depletion of
the antioxidant activity at 24 h postmortem (P<0.05). We also found that mixing
unfamiliar animals, both at the farm and during transport and lairage, triggers
postmortem muscle autophagy, which showed an earlier activation (higher
expression of Beclin 1 and LC3-II/LC3-I ratio at 4 h postmortem followed by a
decreasing pattern of this ratio along first 24 h postmortem) in the muscle
tissues of animals from the MF-UTL and MF-MTL groups, as an adaptive strategy of
the muscle cells for counteracting induced stress. From these results, we propose
that monitoring the evolution of the main biomarkers of autophagy (Beclin 1, LC3
II/LC3-I ratio) and muscle antioxidant defense (TAA, SOD, CAT) in the muscle
tissue within the first 24 h postmortem may help the detection of animal stress
and its potential effect on the postmortem muscle metabolism.
PMID- 25851612
TI - Dichorionic triplet pregnancies: risk of miscarriage and severe preterm delivery
with fetal reduction versus expectant management. Outcomes of a cohort study and
systematic review.
AB - BACKGROUND: In trichorionic pregnancies, fetal reduction from three to two lowers
the risk of severe preterm delivery, but provides no advantage in survival.
Similar data for dichorionic triamniotic (DCTA) triplets is not readily
available. OBJECTIVES: To document the natural history of DCTA triplets and the
effect of reduction on the risk of miscarriage and severe preterm delivery,
compared with expectant management. SEARCH STRATEGY: Systematic search on
MEDLINE, EMBASE, and the Cochrane Library. SELECTION CRITERIA: DCTA triplets with
three live fetuses at 8-14 weeks of gestation, outcome data with expectant
management and/or reduction, miscarriage before 24 weeks of gestation and/or
severe preterm delivery before 32-33 weeks of gestation. DATA COLLECTION AND
ANALYSIS: Five studies were included. Data from these were combined with data
from three centres. MAIN RESULTS: There were 331 DCTA triplets. The miscarriage
rate was 8.9% (95% CI 5.8-13.3%) and the severe preterm delivery rate was 33.3%
(95% CI 27.5-39.7%), with expectant management. The miscarriage rate was 14.5%
(95% CI 7.6-26.2%) with a reduction of the monochorionic pair, 8.8% (95% CI 3.0
23.0%) with a reduction of one fetus of the monochorionic pair, and 23.5% (9.6
47.3%) with a reduction of the fetus with a separate placenta. Severe preterm
delivery rates were 5.5% (95% CI 1.9-14-9%), 11.8% (95% CI 4.7-26.6%), and 17.6%
(95% CI 6.2-41.0%), respectively. CONCLUSIONS: In DCTA triplets, expectant
management is a reasonable choice when the top priority is a liveborn infant.
Where the priority is to minimise severe preterm delivery, the most advisable
option is fetal reduction. Further studies are needed to clarify which particular
technique is advisable to optimise the outcome.
PMID- 25851613
TI - The cytosolic branched-chain aminotransferases of Arabidopsis thaliana influence
methionine supply, salvage and glucosinolate metabolism.
AB - Arabidopsis thaliana possesses six branched-chain aminotransferases (BCAT1-6).
Previous studies revealed that some members of this protein family are involved
in the biosynthesis of branched-chain amino acids and/or in the Met chain
elongation pathway, the initial steps towards the biosynthesis of Met-derived
glucosinolates. We now analyzed branched-chain aminotransferase 6 (BCAT6). In
vivo GFP-tagging experiments strongly suggest this enzyme to be localized to the
cytosol. Substrate specificity assays performed with recombinant enzyme revealed
that BCAT6 transaminates Val, Leu and Ile as well as the corresponding 2-oxo
acids but also transaminates Met and its cognate ketoacid 4-methyl-2
oxobutanoate. We established single (bcat6-1), double (bcat4-2/bcat6-1) and
triple (bcat3-1/bcat4-2/bcat6-1) mutants involving BCAT6 with the latter
exhibiting a clear macroscopic phenotype with smaller plants and abnormal leaf
morphology. Metabolite profiling of these mutants demonstrated that BCAT6 can
contribute to Met chain elongation with the triple mutant line lacking BCAT3, 4
and 6 showing a dramatic reduction of Met-derived glucosinolate species down to
32 and 14% of wild-type levels in plant foliage and seeds, respectively. This
drop in glucosinolate levels is accompanied by a 46-fold increase of free Met,
demonstrating the important role of the three branched-chain aminotransferases in
converting Met to its 2-oxo acid for glucosinolate chain elongation. In addition,
we determined the relative amounts of 5'-deoxy-5'-methylthioadenosine, an
intermediate of the Met recycling pathway. This metabolite accumulated to
relative high amounts in the absence of the cytosolic BCAT4 and BCAT6, suggesting
that cytosolic Met salvage also contributes to the biosynthesis of
glucosinolates.
PMID- 25851614
TI - Discovery, evaluation and distribution of haplotypes and new alleles of the
Photoperiod-A1 gene in wheat.
AB - Photoperiod response in wheat is determined to a large extent by the homoeologous
series of Photoperiod 1 (Ppd1) genes. In this study, Ppd-A1 genomic sequences
from the 5' UTR and promoter region were analysed in 104 accessions of six
tetraploid wheat species (Triticum dicoccoides, T. dicoccum, T. turgidum, T.
polonicum, T. carthlicum, T. durum) and 102 accessions of six hexaploid wheat
species (T. aestivum, T. compactum, T. sphaerococcum, T. spelta, T. macha, T.
vavilovii). This data was supplemented with in silico analysis of publicly
available sequences from 46 to 193 accessions of diploid and tetraploid wheat,
respectively. Analysis of a region of the Ppd-A1 promoter identified thirteen
haplotypes, which were divided in two haplogroups. Distribution of the Ppd-A1
haplogroups and haplotypes in wheat species, and their geographical distributions
were analysed. Polymerase chain reaction combined with a heteroduplex mobility
assay was subsequently used to efficiently discriminate between Ppd-A1 alleles,
allowing identification of the Ppd-A1b haplotypes and haplogroups. The causes of
anomalous migration of Ppd-A1 heteroduplexes in gels were found to be the
localization of mismatches relative to the center of fragment, the cumulative
effect of neighbouring polymorphic sites, and the location of mismatches within
A/T-tracts. Analysis of the Ppd-A1 5' UTR in hexaploid wheat revealed a novel
mutation within the "photoperiod critical" region in a subset of T. compactum
accessions. This putative photoperiod insensitive allele (designated Ppd-A1a.4)
includes a 684 bp deletion which spans region in common with deletions previously
identified in other photoperiod insensitive Ppd1 alleles.
PMID- 25851615
TI - Familial risk for distress and fear disorders and emotional reactivity in
adolescence: an event-related potential investigation.
AB - BACKGROUND: The late positive potential (LPP) is an event-related potential
component that is sensitive to the motivational salience of stimuli. Children
with a parental history of depression, an indicator of risk, have been found to
exhibit an attenuated LPP to emotional stimuli. Research on depressive and
anxiety disorders has organized these conditions into two empirical classes:
distress and fear disorders. The present study examined whether parental history
of distress and fear disorders was associated with the LPP to emotional stimuli
in a large sample of adolescent girls. METHOD: The sample of 550 girls (ages 13.5
15.5 years) with no lifetime history of depression completed an emotional picture
viewing task and the LPP was measured in response to neutral, pleasant and
unpleasant pictures. Parental lifetime history of psychopathology was determined
via a semi-structured diagnostic interview with a biological parent, and
confirmatory factor analysis was used to model distress and fear dimensions.
RESULTS: Parental distress risk was associated with an attenuated LPP to all
stimuli. In contrast, parental fear risk was associated with an enhanced LPP to
unpleasant pictures but was unrelated to the LPP to neutral and pleasant
pictures. Furthermore, these results were independent of the adolescent girls'
current depression and anxiety symptoms and pubertal status. CONCLUSIONS: The
present study demonstrates that familial risk for distress and fear disorders may
have unique profiles in terms of electrocortical measures of emotional
information processing. This study is also one of the first to investigate
emotional/motivational processes underlying the distress and fear disorder
dimensions.
PMID- 25851616
TI - Cost effectiveness of paliperidone palmitate versus oral antipsychotics in
patients with schizophrenia and a history of criminal justice involvement.
AB - OBJECTIVE: Conduct a cost effectiveness analysis for the Paliperidone palmitate
Research In Demonstrating Effectiveness (PRIDE) trial. RESEARCH DESIGN AND
METHODS: PRIDE was a 15 month, prospective, randomized, open-label study in which
once monthly paliperidone palmitate significantly delayed the time to first
treatment failure (healthcare or criminal justice system [HC/CJS] events) versus
oral antipsychotics in recently incarcerated adults with schizophrenia. The
present analysis used a state government perspective and HC/CJS event data that
were collected on a resource use questionnaire (RUQ) every 3 months. MAIN OUTCOME
MEASURES: Since cost information was not collected in the trial, cost estimates
from published literature and an analysis of multistate Medicaid data for CJS and
HC events, respectively, were applied to RUQ event data. Effectiveness and costs
were adjusted to 456 days (trial duration). Incremental cost effectiveness was
calculated as the adjusted cost difference divided by the adjusted effectiveness
difference. RESULTS: Adjusted costs (in US dollars) in the paliperidone palmitate
group (n = 198) and the oral antipsychotic group (n = 193), respectively, were:
non-drug costs $22,331 and $25,027; drug costs $18,592 and $7833; and total costs
$40,923 and $32,860. Adjusted effectiveness differences and corresponding
incremental cost effectiveness per event avoided (in parentheses) for
paliperidone palmitate versus oral antipsychotics were as follows: 0.33 fewer CJS
events ($24,409), 0.13 fewer psychiatric hospitalizations ($60,484), 0.46 fewer
psychiatric hospitalizations or CJS events combined ($17,391), and 0.30 fewer
incarcerations ($26,754). CONCLUSIONS: Costs for HC/CJS events avoided offset 25%
of the greater drug cost for the paliperidone palmitate versus oral antipsychotic
treatment group in this vulnerable population. Use of a recall-dependent RUQ for
event rates and cost estimates instead of actual costs are potential limitations
and may make the results conservative from a state government perspective.
Indirect costs are likely to be substantial for this population, but were not
considered in the analysis.
PMID- 25851617
TI - De novo exon 1 deletion of AUTS2 gene in a patient with autism spectrum disorder
and developmental delay: a case report and a brief literature review.
AB - Exonic deletions disrupting the autism susceptibility candidate 2 (AUTS2) gene
have been demonstrated as causal variants leading to neurodevelopmental disorders
(NDDs) such as autism spectrum disorder (ASD) and developmental delay (DD). Here,
we report on 830 kb de novo deletion at chromosome 7q11.22 in a 4-year-old male
patient with ASD and DD. This deletion disrupts the promoter region and exon 1 of
AUTS2, potentially leading to complete haploinsuffiency of the gene. In addition,
we discuss the clinical presentation of the de novo deletion in the light of the
previous studies describing deletions of AUTS2 in NDDs.
PMID- 25851618
TI - Population structure of humpback whales in the western and central South Pacific
Ocean as determined by vocal exchange among populations.
AB - For cetaceans, population structure is traditionally determined by molecular
genetics or photographically identified individuals. Acoustic data, however, has
provided information on movement and population structure with less effort and
cost than traditional methods in an array of taxa. Male humpback whales
(Megaptera novaeangliae) produce a continually evolving vocal sexual display, or
song, that is similar among all males in a population. The rapid cultural
transmission (the transfer of information or behavior between conspecifics
through social learning) of different versions of this display between distinct
but interconnected populations in the western and central South Pacific region
presents a unique way to investigate population structure based on the movement
dynamics of a song (acoustic) display. Using 11 years of data, we investigated an
acoustically based population structure for the region by comparing stereotyped
song sequences among populations and years. We used the Levenshtein distance
technique to group previously defined populations into (vocally based) clusters
based on the overall similarity of their song display in space and time. We
identified the following distinct vocal clusters: western cluster, 1 population
off eastern Australia; central cluster, populations around New Caledonia, Tonga,
and American Samoa; and eastern region, either a single cluster or 2 clusters,
one around the Cook Islands and the other off French Polynesia. These results are
consistent with the hypothesis that each breeding aggregation represents a
distinct population (each occupied a single, terminal node) in a metapopulation,
similar to the current understanding of population structure based on genetic and
photo-identification studies. However, the central vocal cluster had higher
levels of song-sharing among populations than the other clusters, indicating that
levels of vocal connectivity varied within the region. Our results demonstrate
the utility and value of using culturally transmitted vocal patterns as a way of
defining connectivity to infer population structure. We suggest vocal patterns be
incorporated by the International Whaling Commission in conjunction with
traditional methods in the assessment of structure.
PMID- 25851619
TI - Selective disruption of heparin and antithrombin-mediated regulation of human
factor IX.
AB - BACKGROUND: Interaction with antithrombin and heparin regulates distribution,
activity, and clearance of factor IXa (FIXa). Hemophilia B prophylaxis targets
plasma FIX levels > 1% but neglects extravascular FIX, which colocalizes with
antithrombin-heparan sulfate. OBJECTIVE: Combined mutagenesis of FIX was
undertaken to selectively disrupt heparin- and antithrombin-mediated regulation
of the protease. METHODS: Human FIX alanine substitutions in the heparin (K126A
and K132A) and antithrombin (R150A) exosites were characterized with regard to
coagulant activity, plasma thrombin generation, antithrombin inhibition, and
plasma half-life. RESULTS: Single or combined (K126A/R150A or K132A/R150A)
exosite mutations variably reduced coagulant activity relative to wild-type (WT)
for FIX (27-91%) and FIXa (25-91%). Double mutation in the heparin exosite
(K126A/K132A and K126A/K132A/R150A) markedly reduced coagulant activity (7-21%)
and plasma TG. In contrast to coagulant activity, FIX K126A (1.8-fold), R150 (1.6
fold), and K132A/R150A (1.3-fold) supported increased tissue factor-initiated
plasma TG, while FIX K132A and K126A/R150A were similar to WT. FIXa K126A/R150A
and K132A/R150A (1.5-fold) demonstrated significantly increased FIXa-initiated
TG, while FIXa K132A, R150A, and K126A (0.8-0.9-fold) were similar to WT. Dual
mutations in the heparin exosite or combined mutations in both exosites
synergistically reduced the inhibition rate for antithrombin-heparin. The half
life of FIXa WT in FIX-deficient plasma was remarkably lengthy (40.9 +/-1.4 min)
and further prolonged for FIXa R150A, K126A/R150A, and K132A/R150A (> 2 h).
CONCLUSION: Selective disruption of exosite-mediated regulation by heparin and
antithrombin can be achieved with preserved or enhanced thrombin generation
capacity. These proteins should demonstrate enhanced therapeutic efficacy for
hemophilia B.
PMID- 25851620
TI - Resetting of a Supraventricular Tachycardia by a Ventricular Premature Beat. What
is the Mechanism?
PMID- 25851622
TI - A general salt-templating method to fabricate vertically aligned graphitic carbon
nanosheets and their metal carbide hybrids for superior lithium ion batteries and
water splitting.
AB - The synthesis of vertically aligned functional graphitic carbon nanosheets (CNS)
is challenging. Herein, we demonstrate a general approach for the fabrication of
vertically aligned CNS and metal carbide@CNS composites via a facile salt
templating induced self-assembly. The resulting vertically aligned CNS and metal
carbide@CNS structures possess ultrathin walls, good electrical conductivity,
strong adhesion, excellent structural robustness, and small particle size. In
electrochemical energy conversion and storage such unique features are favorable
for providing efficient mass transport as well as a large and accessible
electroactive surface. The materials were tested as electrodes in a lithium ion
battery and in electrochemical water splitting. The vertically aligned nanosheets
exhibit remarkable lithium ion storage properties and, concurrently, excellent
properties as electrocatalysts for hydrogen evolution.
PMID- 25851623
TI - No association between iron status and self-reported health-related quality of
life in 16,375 Danish blood donors: results from the Danish Blood Donor Study.
AB - BACKGROUND: Health-related quality of life (HRQL) represents people's subjective
assessment of their mental and physical well-being. HRQL is highly predictive of
future health. The effect of iron deficiency without anemia induced by blood
donation on HRQL is presently unknown. The aim was to explore the relationship
between iron status and self-reported mental component score (MCS; SF-12) and
physical component score (PCS; SF-12) in Danish blood donors. STUDY DESIGN AND
METHODS: Complete relevant data, including the 12-item short-form health survey
(SF-12), plasma ferritin levels, age, body mass index, smoking status, C-reactive
protein levels, number of donations in the previous 3 years, and PCS and MCS,
were available for 8692 men and 7683 women enrolled from March 1, 2010, to
December 31, 2010. Multivariable linear and logistic (cutoff at the 10th
percentile) regression analyses were used to assess the relationship between iron
deficiency (ferritin < 15 ng/mL) and MCS and PCS, respectively. Analyses were
performed separately for men and women. RESULTS: There was no significant
relationship between iron deficiency and self-reported mental or physical health.
CONCLUSION: This study found no association between iron stores and self-reported
HRQL among Danish blood donors.
PMID- 25851624
TI - Comparative effects of PEG-containing liposomal formulations on in vivo
pharmacokinetics of streptokinase.
AB - Streptokinase (SK) is an effective thrombolytic agent, but it has a short half
life due to its rapid elimination from the body. In this study, we prepared and
evaluated polyethyleneglycol (PEG)-based liposomal formulations (PEG-liposomes)
containing SK with a view toward prolonging its circulatory half-life. SK-bearing
liposomes (SK-liposomes) were prepared using freeze-thaw method after film
hydration and extrusion techniques, composed of phosphatidylcholine [egg
phosphatidylcholine (EPC), dipalmitoyl PC, or distearoyl PC], cholesterol and
cholesterol-3-sulfate with or without PEG. Their physicochemical properties were
characterized by the measurement of size and zeta potential and incorporation
efficiency. SK-liposomal formulations were applied to rats through a femoral vein
via intravenous administration to compare the effects of liposomal delivery and
PEG on the half-life of SK in blood. Free SK was used as a control. SK activities
in plasma were measured to estimate the amidolytic activity of SK-plasminogen
complex after rupturing liposomes with Triton X-100. Pharmacokinetic parameters
were obtained from SK activity-time profiles. The SK-liposomes had a homogenous
distribution of negatively charged nanoparticles at the range of 10-33% of the
incorporation efficiencies of SK. Among the SK-liposomes, SK-EPC- and SK-EPC/PEG
liposomes had injectable diameters (<200 nm). SK was administered as free SK, SK
EPC-liposomes, or SK-EPC/PEG-liposomes for in vivo study. SK-EPC/PEG-liposomes
had significantly greater the t(1/2), AUC(infinity) and MRT values of SK than SK
alone or SK-EPC-liposomes. These findings suggest that PEG-liposomal
incorporation of SK enhances thrombolytic activity in vivo, and that such
liposomes can be utilized to enhance the pharmacokinetic profiles of other
therapeutic proteins with a short biological half-life.
PMID- 25851625
TI - Self-reported symptoms of attention-deficit/hyperactivity disorder: rate of
endorsement and association with neuropsychological performance in an adult
psychiatric sample.
AB - The lack of specificity of attention-deficit/hyperactivity disorder (ADHD)
symptoms represents a diagnostic challenge, especially when assessing psychiatric
patients reporting a wide range of complaints. Rate of endorsement of ADHD
symptoms, and their association with neuropsychological performance, was examined
in a psychiatric sample of 71 adults, who had been referred for a
neuropsychological evaluation. Patients completed two self-report measures of
ADHD symptoms, the ADHD Self-Report Scale (ADHD-SR) and the Wender Utah Rating
Scale-Short Form, as well as measures of attention, executive functioning,
visuoconstructional ability, and verbal learning and memory. On the ADHD-SR,
74.6% of the sample met the cutoff for inattention or hyperactivity, while 81.7%
met the cutoff for impulsivity. Neuropsychological performance was weakly
associated with self-reported symptoms. Our results suggest that psychiatric
patients commonly report symptoms of inattention, hyperactivity, and impulsivity.
Assessment utilizing multiple sources is necessary to confirm whether self
reported symptoms are indicative of ADHD or reflect other causes.
PMID- 25851626
TI - Circulating tumor DNA as an early marker of therapeutic response in patients with
metastatic colorectal cancer.
AB - BACKGROUND: Early indicators of treatment response in metastatic colorectal
cancer (mCRC) could conceivably be used to optimize treatment. We explored early
changes in circulating tumor DNA (ctDNA) levels as a marker of therapeutic
efficacy. PATIENTS AND METHODS: This prospective study involved 53 mCRC patients
receiving standard first-line chemotherapy. Both ctDNA and CEA were assessed in
plasma collected before treatment, 3 days after treatment and before cycle 2.
Computed tomography (CT) scans were carried out at baseline and 8-10 weeks and
were centrally assessed using RECIST v1.1 criteria. Tumors were sequenced using a
panel of 15 genes frequently mutated in mCRC to identify candidate mutations for
ctDNA analysis. For each patient, one tumor mutation was selected to assess the
presence and the level of ctDNA in plasma samples using a digital genomic assay
termed Safe-SeqS. RESULTS: Candidate mutations for ctDNA analysis were identified
in 52 (98.1%) of the tumors. These patient-specific candidate tissue mutations
were detectable in the cell-free DNA from the plasma of 48 of these 52 patients
(concordance 92.3%). Significant reductions in ctDNA (median 5.7-fold; P < 0.001)
levels were observed before cycle 2, which correlated with CT responses at 8-10
weeks (odds ratio = 5.25 with a 10-fold ctDNA reduction; P = 0.016). Major
reductions (>=10-fold) versus lesser reductions in ctDNA precycle 2 were
associated with a trend for increased progression-free survival (median 14.7
versus 8.1 months; HR = 1.87; P = 0.266). CONCLUSIONS: ctDNA is detectable in a
high proportion of treatment naive mCRC patients. Early changes in ctDNA during
first-line chemotherapy predict the later radiologic response.
PMID- 25851627
TI - Variation in transplacental transfer of tyrosine kinase inhibitors in the human
perfused cotyledon model.
AB - BACKGROUND: The use of tyrosine kinase inhibitors (TKis) during pregnancy in
humans remains rare, and little data are available on their transplacental
passage. Erlotinib and gefitinib are the first-line targeted therapy in case of
stage IV nonsmall-cell lung cancer with an EGFR-activating mutation. There are no
data available regarding the comparative use of these TKis in pregnant patients.
We aimed to compare the transplacental transfer of gefitinib, imatinib and
erlotinib, using the ex vivo method of human perfused cotyledon, and to determine
the placental accumulation of TKis. MATERIALS AND METHODS: Term placentas were
perfused after delivery with gefitinib, imatinib and erlotinib at targeted
maternal concentrations around the steady-state plasma trough concentration (i.e.
500, 1000 and 1500 ng/ml, respectively). Samples from fetal and maternal
circulations were collected in order to monitor TKis concentrations. Main
transfer parameters such as fetal transfer rate (FTR), clearance index (CI) and
placental uptake were assessed. RESULTS: Mean FTR of gefitinib, imatinib and
erlotinib were 16.8%, 10.6% and 31.4%, respectively. Mean CI of gefitinib,
imatinib and erlotinib were 0.59, 0.48 and 0.93, respectively. Placental uptake
in cotyledon was 0.030% %, 0.010% and 0.003% for gefitinib, imatinib and
erlotinib, respectively, corresponding to a mean mass of 27.7 ug for gefitinib,
15.7 ug for imatinib and 6.8 ug for erlotinib. CONCLUSION: The results suggest
that TKis cross the placenta at therapeutic level. Particularly, erlotinib
crosses the placenta at a higher rate than gefitinib or imatinib. All of them
have a very low placental uptake. These data may suggest that gefitinib should be
preferred to erlotinib for the treatment of pregnant woman with lung cancer
harboring an EGFR-activating mutation, during the second and third trimesters of
pregnancy.
PMID- 25851628
TI - Benefit to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2)
targeted therapies in HER2-positive primary breast cancer is independent of
phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status.
AB - BACKGROUND: Assessment of phosphatase and tensin homolog deleted from chromosome
10 (PTEN) might be an important tool in identifying human epidermal growth factor
receptor 2 (HER2)-positive breast cancer patients unlikely to derive benefit from
anti-HER2 therapies. However, studies to date have failed to demonstrate its
predictive role in any treatment setting. PATIENTS AND METHODS: Prospectively
collected baseline core biopsies from 429 early-stage HER2-positive breast cancer
patients treated with trastuzumab, lapatinib, or their combination in the Neo
ALTTO study were stained using two anti-PTEN monoclonal antibodies (CST and
DAKO). The association of PTEN status and PI3K pathway activation (defined as
either PTEN loss and/or PIK3CA mutation) with total pathological complete
response (tpCR) at surgery, event-free survival (EFS), and overall survival (OS)
was evaluated. RESULTS: PTEN loss was observed in 27% and 29% of patients (all
arms, n = 361 and n = 363) for CST and DAKO, respectively. PTEN loss was more
frequently observed in hormone receptor (HR)-negative (33% and 36% with CST and
DAKO, respectively) compared with HR-positive tumours (20% and 22% with CST and
DAKO, respectively). No significant differences in tpCR rates were observed
according to PTEN status. PI3K pathway activation was found in 47% and 48% of
patients (all arms, n = 302 and n = 301) for CST and DAKO, respectively.
Similarly, tpCR rates were not significantly different for those with or without
PI3K pathway activation. Neither PTEN status nor PI3K pathway activation were
predictive of tpCR, EFS, or OS, independently of treatment arm or HR status. High
inter-antibody and inter-observer agreements were found (>90%). Modification of
scoring variables significantly affected the correlation between PTEN and HR
status but not with tpCR. CONCLUSION: These data show that PTEN status
determination is not a useful biomarker to predict resistance to trastuzumab and
lapatinib-based therapies. The lack of standardization of PTEN status
determination may influence correlations between expression and relevant clinical
end points. CLINICAL TRIALS: This trial is registered with ClinicalTrials.gov:
NCT00553358.
PMID- 25851629
TI - ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring
the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer
patients.
AB - BACKGROUND: Lymphopenia is a predictive factor for hematological toxicity,
progression and early death in advanced cancers including metastatic breast
cancer (MBC). CYT107 is a recombinant interleukin 7 (IL-7) (Cytheris, now
Revimmune), well tolerated and able to expand lymphocyte pool in humans. The aims
of this study were to determine the optimal schedule to deliver CYT107 and to
assess its effect on clinical end points. PATIENT AND METHODS: This placebo
controlled, double blind, phase IIa was conducted in MBC patients with <1500/ul
lymphocytes treated with capecitabine. Using a 2-by-2 factorial design, 20
patients were randomly allocated to four arms to receive (i) before chemotherapy:
CYT107 or placebo; then (ii) during chemotherapy: CYT107 or placebo. The primary
end point was CD4+ count changes before and during chemotherapy. Secondary end
points were hematological toxicity, safety, overall response, progression-free
survival (PFS) and overall survival (OS). Quantification and functional
competence of circulating immune cells were also assessed. RESULTS: When
administered before chemotherapy, CYT107 induced a significant increase of CD4+
[+148.1% in CYT107 versus +9.9% in placebo groups, (Wilcoxon, P = 0.002)] and
CD8+ T-cell counts, including both naive and memory subsets. When CYT107 was
administered during chemotherapy, the magnitude of CD4+ and CD8+ increase was
less important. No modulation of immune cell functional competence was observed.
CYT107 was well tolerated with no related >=grade 3 adverse events except 1 fatal
suspected unexpected serious adverse reaction (SUSAR) of uncertain relationship.
Of the 12 cases evaluable for response, 6 of 7 patients (86%) receiving CYT107
before chemotherapy achieved a response or stabilization, whereas two of five
patients (40%) receiving placebo achieved the same result. No significant
difference was observed for PFS or OS. CONCLUSION: In lymphopenic MBC, CYT107
increases CD4+ and other T-cell subset counts without altering their function. A
larger clinical trial to demonstrate its impact on clinical outcome is warranted.
CLINICALTRIALSGOV IDENTIFIER: NCT01362107.
PMID- 25851631
TI - Determining the indications for post mastectomy radiotherapy: moving from 20th
century clinical staging to 21st century biological criteria.
PMID- 25851630
TI - Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal
cancer and potential effects on therapy in the CAPRI GOIM trial.
AB - BACKGROUND: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a
high level of intratumor heterogeneity. We carried out a quantitative assessment
of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to
assess potential clinical implications. PATIENTS AND METHODS: Tumor samples (n =
182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2
wild-type mCRC patients were assessed by next-generation sequencing that allows
quantitative assessment of mutant genes. Mutant allelic frequency was normalized
for the neoplastic cell content and, assuming that somatic mutations usually
affect one allele, the Heterogeneity Score (HS) was calculated by multiplying by
2 the frequency of mutant alleles in neoplastic cells. Therefore, HS virtually
corresponds to the fraction of neoplastic cells carrying a specific mutation.
RESULTS: The KRAS HS ranged between 12 and 260 with mean value of 87.1 and median
value of 84.4, suggesting that in most CRC, the majority of neoplastic cells
carry mutant KRAS. Similar findings were observed for NRAS (HS range 35.5-146.7;
mean 102.8; median 117.1). In contrast, in BRAF (HS range 17.1-120; mean 54.8;
median 54.3) and PIK3CA (HS range 14.3-120; mean 59.5; median 47.3) mutant cases,
only a fraction of neoplastic cells seem to carry the mutant allele. The response
rate was 70% in KRAS mutant patients with an HS <33 (low KRAS; n = 10) and 45.7%
in KRAS HS >33 patients (high KRAS; n = 35); median progression-free survival
were 7.97 and 8.37 months, respectively. Low-KRAS tumors had a higher frequency
of additional mutations in PIK3CA when compared with high-KRAS (6/10 versus
8/35). CONCLUSIONS: KRAS and NRAS mutations are usually present in the majority
of neoplastic cells, whereas BRAF and PIK3CA mutations often affect a limited
fraction of transformed cells. Resistance to cetuximab in low-KRAS patients might
be driven by the complex mutational profile rather than KRAS mutation load.
PMID- 25851632
TI - RECORD-2: phase II randomized study of everolimus and bevacizumab versus
interferon alpha-2a and bevacizumab as first-line therapy in patients with
metastatic renal cell carcinoma.
AB - BACKGROUND: The open-label, phase II RECORD-2 trial compared efficacy and safety
of first-line everolimus plus bevacizumab (EVE/BEV) with interferon plus
bevacizumab (IFN/BEV) in patients with metastatic renal cell carcinoma. PATIENTS
AND METHODS: Previously untreated patients were randomized 1:1 to bevacizumab 10
mg/kg every 2 weeks with either everolimus 10 mg/day (EVE/BEV) or interferon (9
MIU 3 times/week, if tolerated) (IFN/BEV). Tumor assessments occurred every 12
weeks. The primary objective was the assessment of treatment effect on
progression-free survival (PFS), based on an estimate of the chance of a
subsequent phase III trial success (50% threshold for phase II success). RESULTS:
Baseline characteristics were balanced between the EVE/BEV (n = 182) and IFN/BEV
(n = 183) arms. The median PFS was 9.3 and 10.0 months in the EVE/BEV and IFN/BEV
arms, respectively (P = 0.485). The predicted probability of phase III success
was 5.05% (hazard ratio = 0.91; 95% confidence interval 0.69-1.19). The median
duration of exposure was 8.5 and 8.3 months for EVE/BEV and IFN/BEV,
respectively. The percentage of patients discontinuing because of adverse events
(AEs) was 23.4% for EVE/BEV and 26.9% for IFN/BEV. Common grade 3/4 AEs included
proteinuria (24.4%), stomatitis (10.6%), and anemia (10.6%) for EVE/BEV and
fatigue (17.1%), asthenia (14.4%), and proteinuria (10.5%) for IFN/BEV. The
median overall survival was 27.1 months in both arms. CONCLUSIONS: The efficacy
of EVE/BEV and IFN/BEV appears similar. No new or unexpected safety findings were
identified and, with the exception of proteinuria in about one-fourth of the
population, EVE/BEV was generally well tolerated. CLINICAL TRIAL REGISTRY AND
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00719264.
PMID- 25851633
TI - The effect of filgrastim or pegfilgrastim on survival outcomes of patients with
cancer receiving myelosuppressive chemotherapy.
AB - BACKGROUND: Primary prophylaxis with granulocyte colony-stimulating factor (G
CSF) is associated with higher chemotherapy relative dose intensity, which may
lead to improved outcomes; however, the association between G-CSF primary
prophylaxis and overall survival (OS) is not well characterized. This study
assessed the effect of G-CSF primary prophylaxis on patient outcomes in
randomized, controlled, registrational clinical trials of filgrastim and
pegfilgrastim. PATIENTS AND METHODS: Three placebo-controlled and two non
inferiority clinical trials of filgrastim and/or pegfilgrastim in patients
receiving myelosuppressive chemotherapy for lung, breast, or colorectal cancer
were included. The median OS, 6- and 12-month survival rates, and hazard ratios
[HRs; unadjusted Cox model with 95% confidence intervals (CIs)] were estimated
for patients receiving >=1 dose of filgrastim, pegfilgrastim, or placebo.
Comparisons were based on a log-rank test. A fixed-effect meta-analysis assessed
the effect of primary prophylaxis with filgrastim/pegfilgrastim on OS in the
placebo-controlled trials. RESULTS: In patients with lung cancer receiving
filgrastim versus placebo, the median OS was 14.1 versus 11.1 months (HR, 0.81;
95% CI 0.48-1.35; P = 0.412); in patients who crossed over to filgrastim from
placebo after cycle 1, the median OS was 16.9 months (HR, 0.75; 95% CI 0.43-1.28;
P = 0.286). The median OS was inestimable in at least one treatment arm in the
other studies because of the small number of OS events. Where estimable, 6- and
12-month survival rates were generally greater among patients receiving
filgrastim/pegfilgrastim versus placebo. In the meta-analysis of placebo
controlled studies comparing G-CSF primary prophylaxis with placebo in the as
treated analysis sets, the HR (95% CI) for OS was 0.77 (0.58-1.03). CONCLUSIONS:
In this retrospective analysis, OS point estimates were greater among patients
receiving filgrastim versus placebo, but the differences were not statistically
significant. Further studies evaluating patient outcomes with G-CSF prophylaxis
are warranted. CLINICAL TRIAL REGISTRATION: NCT00035594, NCT00094809.
PMID- 25851634
TI - Potential of polymerase chain reaction and galactomannan for the diagnosis of
invasive aspergillosis in patients with febrile neutropenia.
AB - The incidence of invasive aspergillosis (IA) has increased over the last years,
especially in immuncompromised patients with high mortality rates. Because of
difficulties about the diagnosis; serological methods [galactomannan (GM) antigen
test] and polymerase chain reaction (PCR) developed in recent years. MycAssay
Aspergillus PCR performance in the diagnosis of IA was evaluated and compared
with the GM and in-house PCR. This study was conducted with 358 serum samples
obtained from 99 patient with febrile neutropenic episodes who were followed in
haematology and bone marrow transplantation units. Patients were classified by
the European Organization for the Research and Treatment of Cancer/Mycoses Study
Group criteria, 18 of them is proven and probable IA. GM antigen test and two
different real-time PCR; one of them is fist commercial PCR for IA; Mycassay
Aspergillus and the other one is in-house real-time PCR performed. Sensitivity
values were Mycassay Aspergillus PCR, in-house PCR, and GM 65.38%, 11.53% and
23.07%, respectively. The high sensitivity obtained from Mycassay Aspergillus PCR
and sensitivity is increased by using a combination of diagnostic methods. GM
antigen test and real-time PCR could be beneficial for early diagnosis and
treatment of IA. For routine usage of PCR as diagnostic assay more studies needed
in future.
PMID- 25851635
TI - Acute effects of calcium citrate with or without a meal, calcium-fortified juice
and a dairy product meal on serum calcium and phosphate: a randomised cross-over
trial.
AB - Ca supplements, but not dietary Ca, have been associated with increased
cardiovascular risk. This difference could be related to differences in their
acute effects on serum Ca. We therefore examined the effects of Ca from different
sources on serum Ca and phosphate in a randomised, cross-over trial of ten women
(mean age of 69 years). Fasting participants received a single dose of 500 mg of
Ca as citrate, citrate with a meal, fortified juice or a dairy product meal, with
at least 6 d between each intervention. Blood was sampled before and 1, 2, 4 and
6 h after each intervention was ingested. Serum ionised and total Ca increased
significantly from baseline over 6 h. Using calcium citrate fasting as a
comparator, the elevations in ionised and total Ca were similar after fortified
juice, delayed after calcium citrate with a meal and smaller after a dairy
product meal. Serum phosphate and calcium-phosphate product increased from
baseline after calcium citrate with a meal and after a dairy product meal, and
they declined after calcium citrate fasting and after fortified juice. The
elevations in serum Ca in the present study were only slightly different from
those observed after the administration of 1000 mg of Ca in a previous study.
These data indicate that different sources of Ca have different acute effects on
serum Ca and support recommendations that dietary Ca might be safer than
supplements. Whether these differences contribute to differences in
cardiovascular risk requires further study.
PMID- 25851636
TI - The selective dopamine D3 receptor antagonist SB-277011A attenuates drug- or food
deprivation reactivation of expression of conditioned place preference for
cocaine in male Sprague-Dawley rats.
AB - We determined the effect of the selective dopamine D3 receptor antagonist SB
277011A on reactivation of conditioned place preference (CPP) to cocaine elicited
by priming injections of cocaine or exposure to food deprivation stress (21 h) in
male Sprague-Dawley rats. Animals paired with the cocaine-associated chamber
displayed a robust and consistent CPP response. This CPP was extinguished after
repeated pairings of the conditioned stimuli (cocaine-paired chamber contextual
cues) in the absence of the unconditioned stimulus (cocaine). Twenty-four hours
later, the administration of 5 mg kg(-1) i.p. of cocaine (immediately before the
test) or exposure to 21 h of food deprivation reactivated the expression of the
cocaine-induced CPP. In contrast, administration of 1 ml kg(-1) i.p. of vehicle
did not reactivate the CPP response. Administration of the selective dopamine D3
receptor antagonist SB-277011A (3-24 mg kg(-1) i.p.) 30 min before cocaine
administration on the test day produced a significant attenuation of CPP
reactivation. Reactivation of the CPP response produced by food deprivation was
also significantly attenuated by SB-277011A (6 or 12 mg kg(-1) i.p.) given 30 min
before the test session. SB-277011A (12 or 24 mg kg(-1) i.p.) did not itself
produce reactivation of the CPP response. Overall, these results suggest that the
reactivation of the incentive value of drug-associated cues by cocaine or food
deprivation is attenuated by selective antagonism of D3 receptors.
PMID- 25851638
TI - Clinical assessment of drug-drug interactions of tasimelteon, a novel dual
melatonin receptor agonist.
AB - Tasimelteon ([1R-trans]-N-[(2-[2,3-dihydro-4-benzofuranyl] cyclopropyl) methyl]
propanamide), a novel dual melatonin receptor agonist that demonstrates
specificity and high affinity for melatonin receptor types 1 and 2 (MT1 and MT2
receptors), is the first treatment approved by the US Food and Drug
Administration for Non-24-Hour Sleep-Wake Disorder. Tasimelteon is rapidly
absorbed, with a mean absolute bioavailability of approximately 38%, and is
extensively metabolized primarily by oxidation at multiple sites, mainly by
cytochrome P450 (CYP) 1A2 and CYP3A4/5, as initially demonstrated by in vitro
studies and confirmed by the results of clinical drug-drug interactions presented
here. The effects of strong inhibitors and moderate or strong inducers of CYP1A2
and CYP3A4/5 on the pharmacokinetics of tasimelteon were evaluated in humans.
Coadministration with fluvoxamine resulted in an approximately 6.5-fold increase
in tasimelteon's area under the curve (AUC), whereas cigarette smoking decreased
tasimelteon's exposure by approximately 40%. Coadministration with ketoconazole
resulted in an approximately 54% increase in tasimelteon's AUC, whereas rifampin
pretreatment resulted in a decrease in tasimelteon's exposure of approximately
89%.
PMID- 25851639
TI - Living Legends: students' responses to an intergenerational life review writing
program.
AB - The purpose of the study was to examine the effects of participation in the
Living Legends program upon health science students' image of older adults and
interest in working with older people. A multisite quasi-experimental control
group design with a connected qualitative component was used. Program sites
included three Naturally Occurring Retirement Communities (NORCs) and one senior
center. Health science students (n = 43) from two universities and two community
colleges and community-dwelling seniors (n = 39) participated in the program. A
baseline questionnaire was used to ascertain demographic characteristics and
prior type and amount of contact with older adults. The Image of Aging Scale and
Likert-style questions to measure interest in working with older adults were the
primary outcome measures. Written responses to program experiences were also
collected. Analysis of covariance was used to compare changes in Image of Aging
subscale scores from pre- to posttest. Mean change in positive image of older
adults subscale scores was 4.6 (SD = 4.4) for the intervention group and -0.6 (SD
= 4.8) for the control group. The difference between groups was significant (F =
22.0, P < .001), and the effect size was large (Cohen's d = 1.07). Nine of the 22
students in the intervention group had a greater interest in working with seniors
after the program. Qualitative themes that emerged included a positive and
beneficial experience, life lessons, seeing the person beyond the visible, power
of the written word, and shared lives. Living Legends is an effective program to
enhance positive images of older adults in future healthcare professionals and
may have a positive impact on some students with regard to interest in working
with older adults.
PMID- 25851640
TI - Prolonged flare-up of testosterone after administration of a gonadotrophin
agonist to a sex offender: an under-recognised risk?
PMID- 25851641
TI - Negative ion gas-phase chemistry of arenes.
AB - Reactions of aromatic and heteroaromatic compounds involving anions are of great
importance in organic synthesis. Some of these reactions have been studied in the
gas phase and are occasionally mentioned in reviews devoted to gas-phase negative
ion chemistry, but no reviews exist that collect all existing information about
these reactions. This work is intended to fill this gap. In the first part of
this review, methods for generating arene anions in the gas phase and studying
their physicochemical properties and fragmentation reactions are presented. The
main topics in this part are as follows: processes in which gas-phase arene
anions are formed, measurements and calculations of the proton affinities of
arene anions, proton exchange reactions, and fragmentation processes of
substituted arene anions, especially phenide ions. The second part is devoted to
gas-phase reactions of arene anions. The most important of these are reactions
with electrophiles such as carbonyl compounds and alpha,beta-unsaturated carbonyl
and related compounds (Michael acceptors). Other reactions including oxidation of
arene anions and halogenophilic reactions are also presented. In the last part of
the review, reactions of electrophilic arenes with nucleophiles are discussed.
The best known of these is the aromatic nucleophilic substitution (SN Ar)
reaction; however, other processes that lead to the substitution of a hydrogen
atom in the aromatic ring are also very important. Aromatic substrates in these
reactions are usually but not always nitroarenes bearing other substituents in
the ring. The first step in these reactions is the formation of an anionic sigma
adduct, which, depending on the substituents in the aromatic ring and the
structure of the attacking nucleophile, is either an intermediate or a transition
state in the reaction path. In the present review, we attempted to collect the
results of both experimental and computational studies of the aforementioned
reactions conducted since the very beginning of gas-phase negative ion chemistry.
PMID- 25851642
TI - Comparison of High-Fidelity Simulation Versus Didactic Instruction as a
Reinforcement Intervention in a Comprehensive Curriculum for Radiology Trainees
in Learning Contrast Reaction Management: Does It Matter How We Refresh?
AB - RATIONALE AND OBJECTIVES: Simulation-based training has been shown to be a useful
adjunct to standard didactic lecture in teaching residents appropriate management
of adverse contrast reactions. In addition, it has been suggested that a biannual
refresher is needed; however, the type of refresher education has not been
assessed. MATERIALS AND METHODS: This was a prospective study involving 31
radiology residents across all years in a university program. All residents
underwent standard didactic lecture followed by high-fidelity simulation-based
training. At approximately 6 months, residents were randomized into a didactic
versus simulation group for a refresher. At approximately 9 months, all residents
returned to the simulation center for performance testing. Knowledge and
confidence assessments were obtained from all participants before and after each
phase. Performance testing was obtained at each simulation session and scored
based on predefined critical actions. RESULTS: There was significant improvement
in knowledge (P < .002) and confidence (P < .001) after baseline education of
combined didactic and simulation-based training. There was no statistical
difference between the simulation and didactic groups in knowledge or confidence
at any phase of the study. There was no significant difference in tested
performance between the groups in either performance testing session.
CONCLUSIONS: This study suggests that a curriculum consisting of an annual
didactic lecture combined with simulation-based training followed by a didactic
refresher at 6 months is an effective and efficient (both cost-effective and time
effective) method of educating radiology residents in the management of adverse
contrast reactions.
PMID- 25851644
TI - Could Blood Pressure Phobia Go Beyond the White Coat Effect?
AB - BACKGROUND: While it is known that excessive anxiety surrounding the measuring of
blood pressure may preclude an accurate measurement, it is not known whether it
could also lead to phobic avoidance behavior. METHODS: Self-reported information
was collected on 125 individuals who made postings on 5 internet-based medical
forums. RESULTS: Qualitative thematic analysis revealed that these individuals
reported experiencing intense fear associated with the measuring of blood
pressure, that was excessive or irrational and which contributed to avoidance of
medical treatment and interference with life decisions. CONCLUSIONS: Based on
these preliminary observations, we are speculating that these symptoms could be
considered consistent with a diagnosis of a Specific Phobia. Investigations using
quantitative methods, representative samples, and standardized clinical
instruments need to be conducted before definitive conclusions can be reached.
PMID- 25851643
TI - Advanced Breast Imaging Availability by Screening Facility Characteristics.
AB - RATIONALE AND OBJECTIVES: To determine the relationship between screening
mammography facility characteristics and on-site availability of advanced breast
imaging services required for supplemental screening and the diagnostic
evaluation of abnormal screening findings. MATERIALS AND METHODS: We analyzed
data from all active imaging facilities across six regional registries of the
National Cancer Institute-funded Breast Cancer Surveillance Consortium offering
screening mammography in calendar years 2011-2012 (n = 105). We used generalized
estimating equations regression models to identify associations between facility
characteristics (eg, academic affiliation, practice type) and availability of on
site advanced breast imaging (eg, ultrasound [US], magnetic resonance imaging
[MRI]) and image-guided biopsy services. RESULTS: Breast MRI was not available at
any nonradiology or breast imaging-only facilities. A combination of breast US,
breast MRI, and imaging-guided breast biopsy services was available at 76.0% of
multispecialty breast centers compared to 22.2% of full diagnostic radiology
practices (P = .0047) and 75.0% of facilities with academic affiliations compared
to 29.0% of those without academic affiliations (P = .04). Both supplemental
screening breast US and screening breast MRI were available at 28.0% of
multispecialty breast centers compared to 4.7% of full diagnostic radiology
practices (P < .01) and 25.0% of academic facilities compared to 8.5% of
nonacademic facilities (P = .02). CONCLUSIONS: Screening facility characteristics
are strongly associated with the availability of on-site advanced breast imaging
and image-guided biopsy service. Therefore, the type of imaging facility a woman
attends for screening may have important implications on her timely access to
supplemental screening and diagnostic breast imaging services.
PMID- 25851646
TI - The ethics of global clinical trials: In developing countries, participation in
clinical trials is sometimes the only way to access medical treatment. What
should be done to avoid exploitation of disadvantaged populations?
PMID- 25851645
TI - Access to human tissues for research and product development: From EU regulation
to alarming legal developments in Belgium.
PMID- 25851647
TI - Excellence and the new social contract for science: In search for scientific
excellence in a changing environment.
PMID- 25851648
TI - Wnt directs the endosomal flux of LDL-derived cholesterol and lipid droplet
homeostasis.
AB - The Wnt pathway, which controls crucial steps of the development and
differentiation programs, has been proposed to influence lipid storage and
homeostasis. In this paper, using an unbiased strategy based on high-content
genome-wide RNAi screens that monitored lipid distribution and amounts, we find
that Wnt3a regulates cellular cholesterol. We show that Wnt3a stimulates the
production of lipid droplets and that this stimulation strictly depends on
endocytosed, LDL-derived cholesterol and on functional early and late endosomes.
We also show that Wnt signaling itself controls cholesterol endocytosis and flux
along the endosomal pathway, which in turn modulates cellular lipid homeostasis.
These results underscore the importance of endosome functions for LD formation
and reveal a previously unknown regulatory mechanism of the cellular programs
controlling lipid storage and endosome transport under the control of Wnt
signaling.
PMID- 25851650
TI - The use of omega-3 Fatty acids in nonalcoholic Fatty liver disease: the end of
the road or a new beginning?
PMID- 25851649
TI - Healthy rabbits are susceptible to Epstein-Barr virus infection and infected
cells proliferate in immunosuppressed animals.
AB - BACKGROUND: Epstein-Barr virus (EBV) is an oncogenic virus implicated in the
pathogenesis of several human malignancies. However, due to the lack of a
suitable animal model, a number of fundamental questions pertaining to the
biology of EBV remain poorly understood. Here, we explore the potential of
rabbits as a model for EBV infection and investigate the impact of
immunosuppression on viral proliferation and gene expression. METHODS: Six
healthy New Zealand white rabbits were inoculated intravenously with EBV and
blood samples collected prior to infection and for 7 weeks post-infection. Three
weeks after the last blood collection, animals were immunosuppressed with daily
intramuscular injections of cyclosporin A at doses of 20 mg/kg for 15 days and
blood collected twice a week from each rabbit. The animals were subsequently
sacrificed and tissues from all major organs were collected for subsequent
analysis. RESULTS: Following intravenous inoculation, all 6 rabbits seroconverted
with raised IgG and IgM titres to EBV, but viral DNA in peripheral blood
mononuclear cells (PBMCs) could only be detected intermittently. Following
immunosuppression however, EBV DNA could be readily detected in PBMCs from all 4
rabbits that survived the treatment. Quantitative PCR indicated an increase in
EBV viral load in PBMCs as the duration of immunosuppression increased. At
autopsy, splenomegaly was seen in 3/4 rabbits, but spleens from all 4 rabbit were
EBV PCR positive. EBER-in situ hybridization and immunoshistochemistry revealed
the presence of a large number of EBER-positive and LMP-1 positive lymphoblasts
in the spleens of 3/4 rabbits. To a lesser extent, EBER-positive cells were also
seen in the portal tract regions of the liver of these rabbits. Western blotting
indicated that EBNA-1 and EBNA-2 were also expressed in the liver and spleen of
infected animals. CONCLUSION: EBV can infect healthy rabbits and the infected
cells proliferate when the animals are immunocompromised. The infected cells
expressed several EBV-latent gene products which are probably driving the
proliferation, reminiscent of what is seen in immunocompromised individuals.
Further work is required to explore the potential of rabbits as an animal model
for studying EBV biology and tumorigenesis.
PMID- 25851651
TI - Visceral fat necrosis in a newborn after whole body hypothermia.
PMID- 25851652
TI - Abdominoscrotal hydrocele presenting as abdominal pain and mass after trans
scrotal hydrocelectomy.
PMID- 25851653
TI - Large-Scale Examination of Factors Influencing Phosphopeptide Neutral Loss during
Collision Induced Dissociation.
AB - Collision-induced dissociation (CID) remains the predominant mass spectrometry
based method for identifying phosphorylation sites in complex mixtures.
Unfortunately, the gas-phase reactivity of phosphoester bonds results in MS/MS
spectra dominated by phosphoric acid (H3PO4) neutral loss events, suppressing
informative peptide backbone cleavages. To understand the major drivers of H3PO4
neutral loss, we performed robust nonparametric statistical analysis of local and
distal sequence effects on the magnitude and variability of neutral loss, using a
collection of over 35,000 unique phosphopeptide MS/MS spectra. In contrast to
peptide amide dissociation pathways, which are strongly influenced by adjacent
amino acid side chains, we find that neutral loss of H3PO4 is affected by both
proximal and distal sites, most notably basic residues and the peptide N-terminal
primary amine. Previous studies have suggested that protonated basic residues
catalyze neutral loss through direct interactions with the phosphate. In
contrast, we find that nearby basic groups decrease neutral loss regardless of
mobility class, an effect only seen by stratifying spectra by charge-mobility.
The most inhibitory bases are those immediately N-terminal to the phosphate,
presumably because of steric hindrances in catalyzing neutral loss. Further
evidence of steric effects is shown by the presence of proline, which can
dramatically reduce the presence of neutral loss when between the phosphate and a
possible charge donor. In mobile proton spectra, the N-terminus is the strongest
predictor of high neutral loss, with proximity to the N-terminus essential for
peptides to exhibit the highest levels of neutral loss.
PMID- 25851654
TI - Ion-to-Neutral Ratios and Thermal Proton Transfer in Matrix-Assisted Laser
Desorption/Ionization.
AB - The ion-to-neutral ratios of four commonly used solid matrices, alpha-cyano-4
hydroxycinnamic acid (CHCA), 2,5-dihydroxybenzoic acid (2,5-DHB), sinapinic acid
(SA), and ferulic acid (FA) in matrix-assisted laser desorption/ionization
(MALDI) at 355 nm are reported. Ions are measured using a time-of-flight mass
spectrometer combined with a time-sliced ion imaging detector. Neutrals are
measured using a rotatable quadrupole mass spectrometer. The ion-to-neutral
ratios of CHCA are three orders of magnitude larger than those of the other
matrices at the same laser fluence. The ion-to-neutral ratios predicted using the
thermal proton transfer model are similar to the experimental measurements,
indicating that thermal proton transfer reactions play a major role in generating
ions in ultraviolet-MALDI.
PMID- 25851656
TI - Penile rehabilitation following prostate cancer treatment: review of current
literature.
AB - Radical prostatectomy (RP) and radiotherapy (RT) are highly effective in
improving prostate cancer survival. However, both have a detrimental effect on
erectile function (EF). Penile rehabilitation consists of understanding the
mechanisms that cause erectile dysfunction (ED) and utilizing pharmacologic
agents, devices or interventions to promote male sexual function. For the past
decade, many researchers have pursued to define effective treatment modalities to
improve ED after prostate cancer treatment. Despite the understanding of the
mechanisms and well-established rationale for postprostate treatment penile
rehabilitation, there is still no consensus regarding effective rehabilitation
programs. This article reviews a contemporary series of trials that assess penile
rehabilitation and explore treatment modalities that might play a role in the
future. Published data and trials related to penile rehabilitation after RP and
RT were reviewed and presented. Although recent trials have shown that most
therapies are well-tolerated and aid in some degree on EF recovery, we currently
do not have tangible evidence to recommend an irrefutable penile rehabilitation
algorithm. However, advancements in research and technology will ultimately
create and refine management options for penile rehabilitation.
PMID- 25851655
TI - Peroxisome proliferator-activated receptor gamma signaling in human sperm
physiology.
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the
PPARs, which are transcription factors of the steroid receptor superfamily.
PPARgamma acts as an important molecule for regulating energy homeostasis,
modulates the hypothalamic-pituitary-gonadal (HPG) axis, and is reciprocally
regulated by HPG. In the human, PPARgamma protein is highly expressed in
ejaculated spermatozoa, implying a possible role of PPARgamma signaling in
regulating sperm energy dissipation. PPARgamma protein is also expressed in
Sertoli cells and germ cells (spermatocytes). Its activation can be induced
during capacitation and the acrosome reaction. This mini-review will focus on how
PPARgamma signaling may affect fertility and sperm quality and the potential
reversibility of these adverse effects.
PMID- 25851657
TI - Androgen-deprivation therapy alone versus combined with radiation therapy or
chemotherapy for nonlocalized prostate cancer: a systematic review and meta
analysis.
AB - In this paper, we reviewed the long-term survival outcomes, safety, and quality
of-life of androgen-deprivation therapy (ADT) alone versus combined with
radiation therapy (RT) or chemotherapy for locally advanced and metastatic
prostate cancer (PCa). A literature search was performed using OvidSP. Randomized
controlled trials (RCTs) that met the following criteria were included: including
locally advanced or metastatic PCa, comparing ADT alone versus combined with any
treatment method and reporting quantitative data of disease control or survival
outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three
compared ADT versus ADT plus RT (n = 2344) and one compared ADT versus ADT plus
docetaxel-estramustine (n = 413) in locally advanced PCa; two compared ADT versus
ADT plus docetaxel (n = 1175) and two compared ADT versus ADT plus estramustine
(n = 114) in metastatic PCa. For locally advanced PCa, the addition of RT to long
term ADT can improve the outcomes of survival and tumor control with fully
acceptable adverse effects. Specially, the pooled odds ratio (OR) of overall
survival (OS) was 1.43 (95% confidence interval 1.20-1.71) when compared ADT plus
RT with ADT alone (P < 0.0001). For metastatic hormonally sensitive PCa, the
concurrent use of docetaxel plus ADT was effective and safe (pooled OR of OS:
1.29 [1.01-1.65]: P = 0.04). In all, long-term ADT plus RT and long-term ADT plus
docetaxel should be considered as proper treatment option in locally advanced and
metastatic hormonally sensitive PCa, respectively. The major limitation for the
paper was that only eight RCTs were available.
PMID- 25851658
TI - Is serum sex hormone-binding globulin a dominant risk factor for metabolic
syndrome?
AB - This multi-center, cross-sectional study investigated the association between
serum testosterone (T) levels, serum sex hormone-binding globulin (SHBG) levels,
and the risk of metabolic syndrome (MS) in 3332 adult Chinese men. The prevalence
of MS was 34.7%, and men with MS had lower serum levels of total T (TT) and SHBG
than those without MS (P < 0.001). There was no significant difference in serum
free T (FT) levels between subjects with and without MS (P = 0.627). In logistic
regression analysis, the association between MS and serum SHBG levels persisted
after adjusting for age, body mass index (BMI), smoking and drinking status, and
serum TT (odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P<
0.01). However, the association between serum TT level and the risk of MS was
weak after adjusting for age, BMI, SHBG level, and smoking and drinking status
(OR 0.981, 95% CI 0.960-1.007). Our study reveals that both serum TT and SHBG
levels, but not serum FT, are inversely associated with the prevalence of MS and
that serum SHBG is an independent and dominant risk factor for MS.
PMID- 25851659
TI - The hazardous effects of tobacco smoking on male fertility.
AB - The substantial harmful effects of tobacco smoking on fertility and reproduction
have become apparent but are not generally appreciated. Tobacco smoke contains
more than 4000 kinds of constituents, including nicotine, tar, carbonic monoxide,
polycyclic aromatic hydrocarbons, and heavy metals. Because of the complexity of
tobacco smoke components, the toxicological mechanism is notably complicated.
Most studies have reported reduced semen quality, reproductive hormone system
dysfunction and impaired spermatogenesis, sperm maturation, and spermatozoa
function in smokers compared with nonsmokers. Underlying these effects, elevated
oxidative stress, DNA damage, and cell apoptosis may play important roles
collaboratively in the overall effect of tobacco smoking on male fertility. In
this review, we strive to focus on both the phenotype of and the molecular
mechanism underlying these harmful effects, although current studies regarding
the mechanism remain insufficient.
PMID- 25851660
TI - RNA binding proteins in spermatogenesis: an in depth focus on the Musashi family.
AB - Controlled gene regulation during gamete development is vital for maintaining
reproductive potential. During the complex process of mammalian spermatogenesis,
male germ cells experience extended periods of the inactive transcription despite
heavy translational requirements for continued growth and differentiation. Hence,
spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation
of gene expression, facilitated by RNA binding proteins (RBPs), which remain
abundantly expressed throughout this process. One such group of proteins is the
Musashi family, previously identified as critical regulators of testis germ cell
development and meiosis in Drosophila, and also shown to be vital to sperm
development and reproductive potential in the mouse. This review describes the
role and function of RBPs within the scope of male germ cell development,
focusing on our recent knowledge of the Musashi proteins in spermatogenesis. The
functional mechanisms utilized by RBPs within the cell are outlined in depth, and
the significance of sub-cellular localization and stage-specific expression in
relation to the mode and impact of posttranscriptional regulation is also
highlighted. We emphasize the historical role of the Musashi family of RBPs in
stem cell function and cell fate determination, as originally characterized in
Drosophila and Xenopus, and conclude with our current understanding of the
differential roles and functions of the mammalian Musashi proteins, Musashi-1 and
Musashi-2, with a primary focus on our findings in spermatogenesis. This review
highlights both the essential contribution of RBPs to posttranscriptional
regulation and the importance of the Musashi family as master regulators of male
gamete development.
PMID- 25851661
TI - The epididymis re-visited: a personal view.
AB - The sperm maturation and storage functions of the epididymis are important
determinants of ejaculate quality, and perhaps provide an avenue to male
contraception. In the last 50 years, the creation of epididymal fertility
profiles in laboratory animals was followed by recognition of new sperm
maturation-related parameters (organization of the acrosome, of the sperm
plasmalemma, and -S-S- -based structural change) which made it possible to
confirm that a similar pattern of sperm maturation obtains in man. The novel
sperm storage function of the cauda epididymidis in therian mammals is regulated
by androgen, usually in conjunction with the low temperature of the scrotum. The
temperature-dependence of the scrotal cauda is reflected in the secretory and ion
transport functions of the epithelium, in its duct dimensions and so in sperm
storage capacity. Moreover, a variety of indirect evidence suggests that an
elevated temperature of the cauda created by clothing may be compromising its
function in man. The pattern of change in the sperm plasmalemma involving
sterols, and also glycosylphosphatidylinositol-linked macromolecules as
spermatozoa enter the cauda region, may underlie the need for their capacitation
subsequently in the female tract. Further, in a variety of taxa the anatomy of
the scrotum, together with the U-shaped configuration of the epididymis/vas
deferens, suggests that the cauda's storage function may also underlie the
evolution of the scrotum. Finally, despite the still relative paucity of
comparative evidence, we can consider now why the epididymis has come to be
organized as it is.
PMID- 25851662
TI - Mechanisms of fertilization elucidated by gene-manipulated animals.
AB - Capacitation and the acrosome reaction are key phenomena in mammalian
fertilization. These phenomena were found more than 60 years ago. However,
fundamental questions regarding the nature of capacitation and the timing of the
acrosome reaction remain unsolved. Factors were postulated over time, but as
their roles were not verified by gene-disruption experiments, widely accepted
notions concerning the mechanism of fertilization are facing modifications.
Today, although in vitro fertilization systems remain our central research tool,
the importance of in vivo observations must be revisited. Here, primarily
focusing on our own research, I summarize how in vivo observations using gene
manipulated animals have elucidated new concepts in the mechanisms of
fertilization.
PMID- 25851664
TI - Short-term impacts of sodium/glucose co-transporter 2 inhibitors in Japanese
clinical practice: considerations for their appropriate use to avoid serious
adverse events.
AB - Sodium/glucose co-transporter 2 inhibitors (SGLT2i) represent a novel class of
glucose-lowering agents that lower plasma glucose levels through pharmacological
inhibition of glucose reuptake from the kidney, independent of insulin secretion
and action. Clinical trials of SGLT2i demonstrated therapeutic benefits on
glycemic control and bodyweight in individuals with type 2 diabetes, with few
cases of serious adverse events (SAEs). However, a considerable number of SAEs
were reported in patients receiving SGLT2i clinically in Japan during the first 3
months of their use. These included urogenital infections, hypoglycemia and
dehydration. Unexpectedly, serious skin and subcutaneous disorders, mainly
reported as generalized rash or skin eruption, were prominent in patients
receiving SGLT2i, but with unknown mechanisms. There is also concern for
potential SAEs associated with chronic SGLT2i administration, especially in the
non-obese type 2 diabetes characterized by reduced insulin secretion often seen
in East Asia. Chronic SAEs may include severe hypoglycemia due to depletion of
hepatic glycogen storage, acceleration of diabetes-associated sarcopenia and
ketosis/ketoacidosis. The current information on acute SAEs confirms the
importance of caution in the appropriate use of SGLT2i. Furthermore, careful long
term observation of patients receiving SGLT2i is essential to avoid SAEs and for
better clinical use of this drug class.
PMID- 25851665
TI - Vascular causes of sudden death in infancy, childhood, and adolescence.
AB - Vascular causes of sudden death in infancy, childhood, and adolescence range from
primary disorders of the vasculature involving structural compromise, as in
anomalous coronary arteries, to vascular problems that may arise as secondary
phenomena, such as the infectious arteritides. The etiology of the underlying
condition may be understood, as in fatal pulmonary thromboembolism, or it may be
shrouded in mystery, as in idiopathic arterial calcinosis. The absence of a
clinical history indicating an underlying vascular problem in a number of
disorders that may cause sudden childhood death underlines the importance of a
meticulous autopsy examination in such cases.
PMID- 25851663
TI - Tamoxifen stimulates calcitonin-producing thyroid C-cells and prevents trabecular
bone loss in a rat model of androgen deficiency.
AB - Thyroid C-cells produce calcitonin (CT), a hypocalcemic hormone, that acts as an
inhibitor of bone resorption. In this study, we investigated the effects of
tamoxifen (TAM) as a selective estrogen receptor modulator on thyroid C-cells,
trabecular bone and biochemical markers of bone metabolism in an animal model of
androgen deficiency, represented by middle-aged orchidectomized (Orx) rats.
Fifteen-month-old male Wistar rats were divided into: Orx and sham-operated (SO)
groups. Rats from one Orx group were injected subcutaneously with TAM citrate
(Orx + TAM; 0.3 mg kg(-1) b.w.), while the rats from SO and a second Orx group
received vehicle alone, once a day for 3 weeks. The peroxidase-antiperoxidase
method was applied for localization of CT in C-cells. Thyroid C-cells were
morphometrically and ultrastructurally analyzed. An ImageJ image-processing
program was used to measure bone histomorphometric parameters. Blood serum
samples were analyzed for CT, osteocalcin (OC), calcium (Ca2+ ) and phosphorus
(P). Urinary Ca2+ concentrations were measured. TAM treatment significantly
increased thyroid C-cell volume (Vc ) and serum CT when compared with vehicle
treated Orx rats. Analysis of trabecular microarchitecture of the tibia showed
that administration of TAM significantly increased cancellous bone area,
trabecular thickness and trabecular number, whereas trabecular separation was
significantly decreased compared with vehicle-treated Orx rats. Serum OC and
urinary Ca2+ concentrations were significantly lower in comparison with the
control Orx group. These results indicate that in our rat model of androgen
deficiency, TAM stimulated calcitonin-producing thyroid C-cells and increased
trabecular bone mass.
PMID- 25851666
TI - Microscopic findings associated with blood pressure indices in postmortem human
aorta samples from young people (ages 15-34).
AB - Standardized postmortem samples of thoracic and abdominal aortas from traumatic
death victims (aged 15-34 inclusive) were selected according to renal indices of
estimated blood pressure. Half of the males had renal small-artery evidence of
elevated blood pressure, and half did not. The group consisted of an
approximately equal number of black and white males. All of the individuals were
nonsmokers and had similar age, cholesterol, and HDL distribution. Lipid
deposition in the thoracic and abdominal aorta sections was determined
quantitatively by means of computer micromorphometry in sections stained with Oil
Red O. Results showed that there is a marked increase in extracellular lipid
deposition in the intima for those arteries studied with elevated renal indices
of hypertension. In addition, there is significantly more extracellular lipid in
the abdominal aortas in black males than in white males. Also notable was the
finding that the thoracic aorta samples exhibited significantly thicker intimas
and larger intimal areas in the high blood pressure index groups than in the low
blood pressure index groups. These results suggest that the development of
atherosclerotic lesions may be due to an increased deposition of extracellular
lipid in the matrix of the arterial intima.
PMID- 25851667
TI - Analysis of atherosclerotic plaques obtained by coronary atherectomy: Foam cells
correlated positively with subsequent restenosis.
AB - Restenosis following coronary intervention is a complex process the mechanisms of
which remains mostly unknown. Tissue obtained by atherectomy is an important
means to study restenosis. Previous studies on atherectomy-retrieved tissue have
not identified histologic features that correlate with restenosis. We performed
an histopathologic evaluation on atherosclerotic plaque tissue obtained by
atherectomy from 58 patients, all of whom had a 6-month angiographic follow-up.
We identified macrophages and lymphocytes and localized tumor necrosis factor
alpha expression in the tissue by immunohistochemistry. Histopathology was
correlated with late angiographic outcomes. Of 10 histologic features evaluated
in the plaque tissue, only the presence of foam cells, identified in paraffin
sections, correlated positively with restenosis (p = 0.04). Immunohistochemistry
showed that macrophages (p = .07), tumor necrosis factor-alpha (p = .07), and
lymphocytes (p = .14) were more prominent, but not significantly so, in lesions
from patients with foam cells and restenosis than in lesions from patients
without foam cells or restenosis. Thus the presence of foam cells in primary
lesions obtained by atherectomy as identified in paraffin-embedded tissue appears
to be a marker for restenosis.
PMID- 25851669
TI - The center for cardiovascular diseases and comparative medicine opens at the Pig
Research Institute, Taiwan, Republic of China.
PMID- 25851668
TI - Cardiomegaly in a young infant.
PMID- 25851670
TI - Cardiovascular pathology in the land of doges.
PMID- 25851671
TI - Minimally Invasive Plate Osteosynthesis in Open Pediatric Tibial Fractures.
AB - OBJECTIVES: The aim of this study is to investigate the effectiveness and
reliability of limited-contact locking plates in minimally invasive percutaneous
osteosynthesis (MIPO) of the lateral tibia. DESIGN: A retrospective study.
PATIENTS AND METHODS: The retrospective study included 14 patients who were
operatively treated with an MIPO technique due to open tibial fractures between
2006 and 2012. The patients were 11 males and 3 females with a mean age of 13.2
(range, 9 to 16) years. The patients were followed up for a mean period of 2.4
(range, 1 to 5) years. The mechanism of the injuries included a motor vehicle
accident (n=11), a shotgun injury (n=2), and a fall from height (n=1). According
to the Gustilo-Anderson classification, 10 patients had type I (72%), 2 had type
II (14%), and 2 had type III (14%) open fractures. RESULTS: The mean time to
radiologic union was 18 (range, 11 to 32) weeks. No infection was detected that
would require implant removal. No complications such as early epiphyseal closure,
angulation, or limb-length inequality were observed. CONCLUSIONS: Limited-contact
locking plates in MIPO of the lateral tibia is an effective alternative method in
the treatment of open pediatric tibial fractures. LEVEL OF EVIDENCE: Level IV
therapeutic.
PMID- 25851672
TI - Validity and Comprehensibility of Physical Activity Scales for Children With
Sport Injuries.
AB - BACKGROUND: Adult physical activity scales are used with children but may not be
valid in this population. This study assesses the appropriateness and
comprehensibility of currently used physical activity scales in children,
identifies sources of response errors, and suggests scale modifications. METHODS:
Cognitive interviews were conducted with 30 children who had a lower extremity
injury, purposefully sampled based on age and sex. Interviews were conducted to
identify children's comprehension of 6 physical activity questionnaires: Tegner
activity scale, Cincinnati Knee Rating System, KOOS-Child, Marx activity scale,
HSS Pedi-FABS, and KOS sports activity scale. RESULTS: The Tegner scale uses
complex activity level descriptions (eg, competitive vs. recreational sports,
types of sports and inclusion of work-related physical activity). Activity
frequency, description of movement, and sport type in the Cincinnati Knee Rating
System led to response mapping issues in many children. Most children felt the
KOOS-Child pictures depicting activities were helpful, but not all found the 7
day timeframe relevant. Whereas, most children found the Marx scale and HSS Pedi
FABS items clear, concise, and easy to answer. Children reported difficulties
differentiating between endurance and duration items used in the HSS Pedi-FABS.
The consistent response format of the KOS sports activity scale was considered a
positive attribute although children had trouble comprehending terms such as
grating and grinding. CONCLUSIONS: Children found some scales too difficult to
answer, whereas others required modifications, particularly in general
instruction, language, question format, and mapping (matching an answer to
potential options) to adapt to the specific needs of children. LEVEL OF EVIDENCE:
Level II.
PMID- 25851673
TI - Arthroscopic Lateral Retinacular Release in Adolescents With Medial
Patellofemoral Ligament-centered Knee Pain.
AB - BACKGROUND: The medial patellofemoral ligament (MPFL) has been implicated as a
common pain generator in adolescents with anterior knee pain. The purpose of this
study is to report the clinical outcomes of arthroscopic lateral retinacular
release (ALRR) for refractory MPFL-centered pain and to identify risk factors for
poor outcomes and surgical failures. METHODS: A single-surgeon database was
queried to identify all patients undergoing ALRR. Inclusion criteria included
minimum 12-month follow-up and ALRR performed for MPFL pain rather than for
generalized anterior knee pain or patellar instability. All patients had
persistent MPFL-centered pain despite participating in a nonsurgical protocol
before surgery. Primary outcomes included International Knee Documentation
Committee (IKDC) subjective score and need for further surgery, typically tibial
tubercle osteotomy (TTO). RESULTS: Eighty-eight knees in 71 patients [66 female,
5 male; average age, 15.7 y (range, 8.4 to 20.2 y)] were included. Average follow
up was 59 months (range, 12 to 138 mo). Average preoperative IKDC score was 41.9
(range, 18.4 to 67.8), whereas average postoperative IKDC score was 77.8 (range,
11.5 to 98.9; P<0.01). Postoperative IKDC scores were worse in patients with a
preoperative sulcus angle of <134 degrees than those with sulcus angle of >=134
degrees (69.9+/-22.1 vs. 82.0+/-12.5, P=0.04). Lower preoperative IKDC score
correlated negatively with improvement of IKDC score postoperatively (r=-0.40,
P<0.05). Seventeen knees (19.3%) subsequently underwent TTO for persistent
symptoms. Patients who ultimately required TTO were younger than patients who did
not (14.8+/-1.5 vs. 15.9+/-2.1; P=0.04) and had lower mean preoperative
Blackburne-Peel ratio (0.95+/-0.25 vs. 1.11+/-0.24; P=0.02). CONCLUSIONS: This
study demonstrates that patients with refractory MPFL-centered knee pain had
significant improvements in clinical outcomes after undergoing ALRR at mean 5
years' follow-up. Poor outcomes and surgical failures were associated with lower
preoperative IKDC score, younger age, lower preoperative Blackburne-Peel ratio,
and sulcus angle of <134 degrees. Outcomes were not recorded prospectively, but
mean IKDC scores <60 months postoperatively were similar to those collected >=60
months after surgery (80.4 vs. 78.3, P=0.15). LEVEL OF EVIDENCE: Level IV.
PMID- 25851674
TI - Early Career Experience of Pediatric Orthopaedic Fellows: What to Expect and Need
for Their Services.
AB - INTRODUCTION: A dramatic increase in the number of pediatric orthopaedic fellows
being trained has led to concerns that there may be an oversupply of pediatric
orthopaedists. The purpose of this study was to determine whether this perception
is accurate and whether the practice expectations of recent pediatric fellowship
graduates are being met by surveying recent pediatric fellowship graduates about
their early practice experiences. METHODS: A 36-question survey approved by the
Pediatric Orthopaedic Society of North America (POSNA) leadership was
electronically distributed to 120 recent graduates of pediatric orthopaedic
fellowships; 81 responses were ultimately obtained (67.5% response rate).
RESULTS: Almost all (91%) of the respondents were very or extremely satisfied
with their fellowship experience. Half of the respondents had at least 1 job
offer before they entered their fellowships. After completion of fellowships, 35%
received 1 job offer and 62.5% received >=2 job offers; only 2.5% did not receive
a job offer. Most reported a practice consisting almost entirely of pediatric
orthopaedics, and 93.5% thought this was in line with their expectations; 87%
indicated satisfaction with their current volume of pediatric orthopaedics, and
85% with the complexity of their pediatric orthopaedic cases. Despite the high
employment percentages and satisfaction with practice profiles, nearly a third
(28%) of respondents replied that too many pediatric orthopaedists are being
trained. CONCLUSIONS: Positive messages from this survey include the satisfaction
of graduates with their fellowship training, the high percentage of graduates who
readily found employment, and the satisfaction of graduates with their current
practice environments; this indicates that the pediatric orthopaedic job
environment is not completely saturated and there are continued opportunities for
graduating pediatric fellows despite the increased number of fellows being
trained. Although not determined by this study, it may be that the stable demand
for pediatric orthopaedic services is being driven by the expansion of the scope
of practice as well as subspecialization within the practice of pediatric
orthopaedics.
PMID- 25851675
TI - A Preliminary Study to Assess Whether Spinal Fusion for Scoliosis Improves Carer
assessed Quality of Life for Children With GMFCS Level IV or V Cerebral Palsy.
AB - BACKGROUND: Scoliosis affects 50% of children with Gross Motor Function
Classification System (GMFCS) level IV or V cerebral palsy (CP). In children with
complex neurodisability following intervention, the WHO considers quality of life
(QoL) should be assessed to aid decision-making and assess the effects. This
study assesses whether scoliosis surgery improves carer-assessed QoL for children
with severe CP. METHODS: Retrospective review of 33 children (16 male:17 female)
with GMFCS level IV/V CP and significant scoliosis. Fifteen underwent
observational treatment during childhood, and 18 underwent surgery. Questionnaire
and radiographic data were recorded over a 2-year period. The carer-completed
Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)
questionnaire was used to assess QoL. RESULTS: In the observational group, Cobb
angle and pelvic obliquity increased from 46 (40 to 60) and 8 degrees (0 to 28)
to 62 (42 to 94) and 12 degrees (1 to 35). Mean CPCHILD score decreased from 50
(30 to 69) to 48 (27 to 69) (P<0.05). In the operative group, Cobb angle and
pelvic obliquity decreased from 78 (52 to 125) and 14 degrees (1 to 35) to 44 (16
to 76) and 9 degrees (1 to 24). Mean CPCHILD score increased from 45 (20 to 60)
to 58 (37 to 76) (P<0.05). Change in pain, and not presence of associated
impairments, was the most significant factor affecting QoL changes for children
in both groups. There was no difference in mobility, GMFCS level, feeding, or
communication in either group before and after treatment. CONCLUSIONS:
Nonoperative treatment for children with GMFCS level IV/V CP and a significant
scoliosis was associated with a small decrease in carer-assessed QoL over 2
years. Spinal fusion was associated with an increase in QoL. Change in pain was
the most significant factor affecting QoL changes, and is therefore an important
factor to consider when deciding upon surgery. LEVEL OF EVIDENCE: Level III
therapeutic retrospective study.
PMID- 25851676
TI - Sonographic Assessment of Hip Swaddling Techniques in Infants With and Without
DDH.
AB - BACKGROUND: The purpose of this single-examination pilot study was to confirm the
ability to perform hip sonography while swaddled and to ascertain whether the
various swaddling techniques influenced hip position and dynamics. METHODS:
Dynamic sonography was used to evaluate 30 infants in both swaddled and
unswaddled positions who were being seen in clinic for suspected or documented
developmental dysplasia of the hip. A "treatment group" of 16 infants (32 hips)
treated in a Pavlik harness and a "nontreatment group" of 14 untreated infants
(28 hips) were studied.Criteria for comparing sonographic results between
swaddled and unswaddled hip positions included femoral head position,
instability, and range-of-motion restriction. RESULTS: Tight swaddling with a
blanket was applied in 11 "nontreatment group" cases (20 hips; in 2 cases, only 1
hip studied) and produced limited flexion and abduction. One unstable left hip
dislocated when tightly swaddled. Safe swaddling technique in 12 cases (24 hips)
showed no limitation of flexion and abduction of the legs and no change in
stability by sonography. Commercial swaddling products appeared to mildly
restrict leg motion in 14 hips, but there was no change in hip position in the
"nontreatment group." However, the commercial swaddling products changed the hip
position in 3 Pavlik harness cases. CONCLUSIONS: Swaddling techniques that allow
a free range of leg motion may not affect hip stability in normal infants or
those being treated with Pavlik harness. Swaddling with restricted leg motion
increases potential for hip instability. Tight swaddling dislocated 1 unstable
hip, and commercial swaddling products judged to apply only mild restriction of
leg motion negatively impacted 3 cases being treated for developmental dysplasia
of the hip with Pavlik harness. On the basis of this pilot study, we advise
caution when swaddling infants, especially with techniques that restrict leg
motion. Further study of the long-term effects of swaddling is warranted. LEVEL
OF EVIDENCE: Level II.
PMID- 25851677
TI - Risk Factors of Refracture and Morbidity During Removal of Titanium Pediatric
Proximal Femoral Locking Plates in Children With Cerebral Palsy.
AB - BACKGROUND: Pediatric proximal femoral locking plates (PFLPs) are widely used
when performing proximal femoral osteotomy in children with cerebral palsy (CP).
The purpose of this study is to report the difficulties and risk factors of
titanium PFLPs removal in CP. METHODS: PFLP removal was performed in 58 hips of
33 patients (17 males, 16 females). The mean age at the time of surgery (plate
removal) was 10.9 (range, 5.7 to 19.2) years. The patients were divided into 2
groups as group 1 and 2, if any difficulty was observed during surgery or not.
RESULTS: Difficulty was not detected in 42 (72.4%) hips (group 1). Difficulties
were encountered in 16 (27.6%) hips (group 2). A total of 364 screws were used
(259 in group 1, 105 in group 2). The mean plate screw density ratios were 0.88
in group 1 and 0.94 in group 2. The difference between group 1 and 2 was
statistically significant. The mean duration between the insertion and removal of
the PFLP was 14.9 months (11.9 mo in group 1, 22.7 mo in group 2). The difference
between group 1 and 2 was statistically significant. The screw heads were cut and
the shafts were left in the bone in 4 hips (4 screws); 3 of these 4 screws were
calcar screws. Therefore, calcar screw application can be accepted as a handicap
for screw removal. CONCLUSIONS: As a conclusion, this study suggested that
difficulty in titanium PFLP removal in CP is common and PFLP removal is not a
harmless procedure. A longer time from internal fixation to removal, increased
plate screw density ratio, and calcar screw application are risk factors for
difficulties in titanium PFLP removal in CP. LEVEL OF EVIDENCE: Level III.
PMID- 25851678
TI - First 50 Pediatric and Adolescent Elbow Arthroscopies: Analysis of Indications
and Complications.
AB - BACKGROUND: Elbow arthroscopy is a challenging, yet extremely productive
procedure in orthopaedic sports medicine. The severely confined anatomy of the
pediatric and adolescent elbow is particularly prone for perioperative
complications. This study focuses on the indications and complications of the
first 50 elbow arthroscopies in skeletally immature patients done in a
specialized pediatric orthopaedic department. PURPOSE: To review analysis of
indications and complications in pediatric and adolescent elbow arthroscopy. We
hypothesized that the complication rate in these patients is similar to adults.
METHODS: Data on 50 consecutive elbow arthroscopies were prospectively gathered
in a dedicated database and retrospectively analyzed for indications and
perioperative complications. All procedures were performed by a surgeon trained
in orthopaedic sports medicine. RESULTS: A total of 26 boys and 24 girls with a
mean age of 13.6+/-3.3 years at the time of surgery and a minimum follow-up of 1
year were included.Fifty-eight percent were treated for osteochondritis
dissecans, 24% for arthrofibrosis, 14% for a congenital disorder, and 4% for a
posttraumatic problem other than arthrofibrosis. The complication rate was 8%,
including 3 cases of transient neuropraxia and 1 superficial wound infection.
There were no major complications such as septic arthritis, vascular injury, or
permanent nerve damage. All complications resolved fully with conservative
treatment, no revision were required. DISCUSSION: Although osteochondritis
dissecans is still the leading reason for such surgery, fractures and
posttraumatic conditions are becoming more important. With a rate of 5% to 8% of
minor, fully resolving complications such an increase is not a reason for
concerns. LEVEL OF EVIDENCE: Level IV-case series.
PMID- 25851679
TI - Are Orthopaedic Residents Competent at Performing Basic Nonoperative Procedures
in an Unsupervised Setting? A "Pop Quiz" of Casting, Knee Arthrocentesis, and
Pressure Checks for Compartment Syndrome.
AB - BACKGROUND: Many patient care procedures are routinely performed by orthopaedic
residents while not directly supervised by attending physicians. However,
resident competence to perform these procedures is often presumed and not
confirmed by objective measures. The purpose of this study was to formally
evaluate 3 basic pediatric orthopaedic procedures commonly performed without
attending supervision. METHODS: All orthopaedic residents (n=20) were asked to
complete 3 procedures (placement and removal of a short arm cast, aspiration of a
knee joint, and compartment pressure checks of a leg) under direct attending
supervision. Attending faculty developed a checklist for each procedure, listing
the appropriate steps required and criteria with which to assess the final
results. Scores were calculated, including means and SDs. Change in score by
postgraduate year level was determined by simple linear regression. RESULTS: The
mean score for short arm cast application and removal was 6.2 of a total possible
score of 8, with an average 1.1 increase in score per year of training (P<0.001).
Uneven cast padding and lack of full thumb motion were the most common reasons
for losing points. Knee joint aspiration had an average score of 6.2 of 7, with
an average increase in score of 0.3 per year of training (P=0.046). Lack of
equipment preparation and not donning gloves in a sterile manner were the most
common reasons for losing points. Measure of leg compartment pressures had an
average score of 9.7 of 12, with an average increase in score of 0.5 per increase
in year of training (P=0.087). Injecting an inappropriate amount of fluid and not
recording measurements were the most common reasons for losing points.
CONCLUSIONS: The ability of a resident to appropriately perform certain
procedures without direct supervision improves with advancing level of training.
The most junior residents might not appropriately be placing short arm casts,
aspirating knee joints, or checking compartment pressures of the leg. LEVEL OF
EVIDENCE: Level II-Diagnostic.
PMID- 25851680
TI - Stuffed Animals in the Operating Room: A Reservoir of Bacteria With a Simple
Solution.
AB - BACKGROUND: Despite hand washing and other protocols surgical-site infections
(SSIs) have not been eliminated. This implies that either current measures are
not effective or there are alternative sources of bacterial exposure to the
surgical wound. In this study we tested the hypothesis that stuffed animals or
other items allowed to accompany pediatric patients to the operating room as a
way to ease anxiety may represent a reservoir of bacteria. METHODS: Stuffed
animals brought into the operating room and stuffed animals that were washed and
dried in a conventional washer/dryer and placed in clean sealable plastic bags
were swabbed and bacterial colonies were quantified. Results were reported as no
growth, light growth, moderate growth, and heavy growth. RESULTS: All stuffed
animals showed bacterial growth. A total of 79% of stuffed animals were
effectively "sterilized" by a single wash and dry cycle in a conventional home
washer/dryer. Sterilized stuffed animals remained sterile after being packed in a
sealed bag for 24 hours. CONCLUSIONS: These results indicate that items of
comfort, such as stuffed animals, brought into the operating room with a
benevolent purpose may represent a reservoir of bacteria that could lead to
unwanted SSI. Washing an item of comfort 1 day before surgery effectively
sterilizes that item of comfort. Future studies will be needed to determine a
correlation between "culture positive" stuffed animals and SSI or if providing a
child with a "sterile" stuffed animal reduces SSI.
PMID- 25851681
TI - Outcomes of Orthopaedic Surgery With and Without an External Femoral Derotational
Osteotomy in Children With Cerebral Palsy.
AB - BACKGROUND: Ambulatory children with cerebral palsy (CP) often present with
multiple deviations in all planes including increased internal hip rotation
during gait. Excessive femoral anteversion is a common cause of deviation managed
surgically with an external femoral derotational osteotomy (FDO). The purpose of
this study was to evaluate the gait and functional outcomes of a group of
subjects with CP who underwent surgical intervention that included an FDO
compared with a match group with indications of internal hip rotation that did
not receive an FDO. METHODS: For this retrospective study, subjects were
identified from the Motion Analysis Laboratory database that had orthopaedic
surgery including an FDO (FDO group). A control group was established from a
chart review identifying subjects that had indications for an FDO, but did not
have this surgery (No-FDO group). All subjects had preoperative and postoperative
gait studies. Subjects categorized as Gross Motor Function Classification System
(GMFCS) levels I and II in both FDO and No-FDO groups were combined for analysis.
Subjects rated as GMFCS level III were analyzed separately. Preoperative to
postoperative kinematic and kinetic variables, Gait Deviation Index, net oxygen
cost, and PODCI scores were analyzed with paired t tests. RESULTS: Typical
sagittal plane kinematic variables improved significantly by equivalent
magnitudes for both FDO and No-FDO groups (GMFCS I/II and III). Transverse plane
improvements were only seen for the FDO group (GMFCS I/II and III). The Gait
Deviation Index, an overall index of kinematics, improved by a significantly
greater amount for the FDO group across GMFCS levels I/II and III. Net oxygen
cost improved for both FDO and No-FDO for GMFCS I/II. PODCI scores improved for
FDO and No-FDO in GMFCS I/II, but only the FDO group for GMFCS III. CONCLUSIONS:
For children with CP, inclusion of an FDO in the surgical intervention, when
indicated, resulted in improved outcomes. Overall gait kinematic improvements
were significantly greater when an FDO was included in the surgical management.
LEVEL OF EVIDENCE: Level III-retrospective comparative study.
PMID- 25851682
TI - Fractures at Diagnosis in Infants and Children With Osteogenesis Imperfecta.
PMID- 25851683
TI - Characterization of Hip Morphology in Children With Mucopolysaccharidosis Types I
and II.
AB - BACKGROUND: The purpose of this study is to describe the natural history of hip
morphology in patients with mucopolysaccharidoses (MPS) I and MPS II.
METHODOLOGY: This is a retrospective radiographic analysis of 88 hips in 44
children with MPS I and II. Radiographs were examined to determine hip migration,
femoral head sphericity, and acetabular dysplasia at different ages throughout
childhood. In individual hips, change in morphology and rate of change were
analyzed. RESULTS: There was a high rate of hip migration and femoral head
dysplasia in both MPS I and MPS II. Progressive migration was seen in three
quarters of hips and progressive femoral head deformity in over half of hips.
Acetabular dysplasia was variable, ranging from normal to severely dysplastic,
but did not change with time. Overall, hips were more dysplastic in MPS I than
MPS II. CONCLUSIONS: Hip morphology is variable in MPS I and MPS II ranging from
almost normal to severely dysplastic. Some hips do not deteriorate with time and
thus surgical intervention may not be necessary in all cases. Deterioration is
slow allowing time to plan a holistic approach to treatment. LEVEL OF EVIDENCE:
Level IV-case series.
PMID- 25851684
TI - Utilizing the "Stable-to-be Vertebra" Saves Motion Segments in Growing Rods
Treatment for Early-Onset Scoliosis.
AB - BACKGROUND: There is no consensus on the selection of distal instrumentation
levels in growing rod surgery. Many surgeons utilize the stable zone of
Harrington, but there is not overwhelming evidence to support this preference.
The aim of this study was to determine the value of bending/traction radiographs
in selection of distal instrumentation levels of a growing rod construct in
children with idiopathic or idiopathic-like early-onset scoliosis (EOS). METHODS:
Twenty-three consecutive patients with idiopathic or idiopathic-like EOS who
underwent growing rod surgery at 2 separate institutions between 2006 and 2011
were included. Lengthening procedures were performed periodically at 6-month
intervals. Analyses were performed retrospectively for age at index surgery,
follow-up period, and radiographic measurements. Lower instrumented levels,
neutral vertebra, stable vertebrae (SV), and stable-to-be vertebrae (StbV) were
identified on the preoperative radiographs. Coronal Cobb angles, tilt of lower
instrumented vertebra (LIV) and LIV+1, and disk wedging under the LIV and LIV+1
were measured on the early postoperative and latest follow-up radiographs.
RESULTS: Average age at index surgery was 83.6 months. Mean follow-up period was
68.1 months. Initial analysis showed that the relationship of LIV to the StbV was
a better predictive of LIV+1 tilt than the SV at the final follow-up. Therefore,
the patients were grouped according to the relationship of the LIV to the StbV.
LIV was the StbV in 9 patients, proximal to the StbV in 8 patients, and distal to
the StbV in 6 patients. At the latest follow-up, tilt of LIV+1 exceeded 10
degrees in 7 of the 8 patients where LIV was proximal to the StbV, whereas only
in 1 of 9 patients where LIV was StbV, and in none of the 6 patients where LIV
was distal to the StbV. The data indicate that selection of the StbV as the LIV
could spare an average of 1.8 vertebral segments when compared with the SV, as
StbV is never distal but almost always proximal to the SV. CONCLUSIONS: Choosing
the StbV as the LIV saves motion segments and prevents distal adding on, while
providing satisfactory deformity correction in idiopathic and idiopathic-like
EOS. LEVEL OF EVIDENCE: Level III-retrospective comparative study.
PMID- 25851685
TI - Do Surgical Times and Efficiency Differ Between Inpatient and Ambulatory Surgery
Centers That are Both Hospital Owned?
AB - PURPOSE: The aim of this study was to examine the differences in primary anterior
cruciate ligament reconstruction (ACLR) surgical time and operation room (OR)
work efficiency between inpatient and ambulatory facilities within the same
institution. METHODS: Patients studied included those who underwent primary ACLR
at either the inpatient hospital or the ambulatory facility by a single
orthopaedic surgeon on elective surgery days. Time variables were calculated for
ACLR to compare the 2 facilities. The OR work efficiency was calculated as the
percentage of work that was completed before mid-day that was determined by the
midpoint of the surgical day at each facility. RESULTS: Two hundred twenty-seven
ACLR surgeries were performed on 187 elective surgery days, 153 surgeries at the
inpatient facility and 74 at the outpatient facility. The mean age at the time of
surgery was 14.9+/-2.2 years. The ACLR surgeries at the ambulatory facility were
of shorter duration than those at the inpatient facility (P<0.0001). One OR was
most commonly utilized and 2 to 3 surgeries were performed on most surgery days
at both facilities. Seven nurses served as alternating circulators at the
ambulatory facility compared with 41 nurses serving in the same capacity at the
inpatient facility. The median turnover time was longer at the inpatient facility
compared with the ambulatory facility. OR work efficiency (work done before mid
day) was 72.5% at the ambulatory facility and 49.5% at the inpatient facility,
P<0.0001. If 2 ACLR surgeries were performed consecutively, the surgery day
lasted for 6 hours at the hospital-owned ambulatory surgery center compared with
9 hours at the inpatient hospital. CONCLUSIONS: Despite the common variables of
the same surgeon performing the same surgery at facilities owned by the same
institution primarily working in a single OR, differences exist in OR procedure
time and work efficiency. LEVEL OF EVIDENCE: Level III.
PMID- 25851686
TI - Disproportionate Participation of Males and Females in Academic Pediatric
Orthopaedics: An Analysis of Abstract Authorship at POSNA 2009-2013.
AB - BACKGROUND: Despite increasing numbers of female orthopaedic surgeons, we
hypothesized that women were not actively participating at national and
international meetings in numbers proportional to their membership. METHODS: A
retrospective review of the 2009-2013 POSNA Annual Meeting Final Programs was
performed. The following information was recorded for all members: name, sex,
membership level, years of membership, and if the individual was an author on at
least 1 abstract. To compare proportion of abstract authorship between sexes
across years, while controlling for years of membership, general estimating
equations with a binomial model and logit link were used. The study population
was limited to candidate and active POSNA members only, as this group represents
the most active practicing pediatric orthopaedic surgeons. RESULTS: Over the 5
year period studied, females comprised 16.6% (204/1227) of the total POSNA
membership and 20.9% (184/880) of members at candidate and active status. The
percentage of females with candidate or active member status in POSNA who had at
least 1 abstract presentation during the 5 years was 37% and this was
significantly lower (P=0.003) than the percentage of men (49%) who presented at
least 1 abstract. Analysis across the 5 years showed a consistent difference
between the sexes with no trend of convergence in abstract rates (P=0.65).
Controlling for years membership, female members still presented abstracts at
lower rates than their male colleagues (P=0.002). CONCLUSIONS: Female members of
POSNA, in the most active part of their careers, participated at significantly
lower rates than their male peers as accepted abstract authors for the 2009-2013
POSNA meetings than would be expected for their proportional size of total
membership.
PMID- 25851687
TI - Compartment Pressures in Children With Normal and Fractured Forearms: A
Preliminary Report.
AB - INTRODUCTION: Acute compartment syndrome (ACS) can lead to irreversible damage if
fasciotomy is not performed in a timely manner. Needle manometry is a tool to
confirm suspected ACS. The threshold for compartment pressures that can be
tolerated has been debated. The aim of this study is to assess the normal
compartment pressures in noninjured forearms of children. Further, we sought to
quantify the maximum tolerable compartment pressures in fractured forearms of
children, thus establishing a baseline and providing guidance in evidence-based
decision making to evaluate children with suspected ACS. METHODS: This
prospective study included children up to the age of 16 years with forearm
fractures that needed reduction with or without osteosynthesis. Between June 2009
and March 2013, 41 children were included. Mean age was 9.25 years (range, 4 to
15.4 y). We used needle manometry to measure the pressures in the superficial and
deep volar as well as in the dorsal compartments (DCs) on both the forearms. The
mean pressures between compartments in healthy versus injured arms were analyzed
using a 1-sided, paired t test. RESULTS: On the injured side, the mean
compartment pressure was 19.12 mm Hg (range, 3 to 49 mm Hg) in the deep volar
compartment, 15.56 mm Hg (range, 5 to 37 mmHg) in the DC, and 14.8 mm Hg (range,
2 to 35 mm Hg) in the superficial volar compartment. On the noninjured side, the
mean compartment pressure was 12.9 mm Hg (range, 6 to 31 mm Hg) in the DC, 10.22
mm Hg (range, 3 to 22 mm Hg) in the deep volar compartment, and 9.66 mm Hg
(range, 3 to 21 mm Hg) in the superficial volar compartment. We measured an
absolute compartment pressure of >30 mm Hg in 15 patients on the fractured side.
Three of them had an absolute compartment pressure of >45 mm Hg. Only 1 had ACS.
This patient underwent fasciotomy and was excluded for further analysis. On
follow-up (mean, 24.84 mo), no patient was found to have any sequelae of ACS.
DISCUSSION: This is the first study to report normal compartment pressure
measurements in noninjured forearms and in fractured forearms without clinical
suspicion of ACS in children.The mean compartment pressure measured in the deep
volar compartment (DVC) in healthy children was 10.22 mm Hg (range, 3 to 22 mm
Hg) and therefore slightly higher than in adults. Some children with fractures
tolerated absolute compartment pressures >30 mm Hg without clinical signs of ACS.
Fasciotomy in children under close observation could eventually be delayed
despite surpassing the accepted pressure limits for adults. LEVEL OF EVIDENCE:
Level I-prognostic.
PMID- 25851688
TI - Reliability and Effectiveness of Smartphone Technology for the Diagnosis and
Treatment Planning of Pediatric Elbow Trauma.
AB - BACKGROUND: Mobile imaging, such as viewing radiographs as text messages, is
increasingly prevalent in clinical settings. The purpose of this study was to
determine whether remote diagnosis of pediatric elbow fractures using smartphone
technology is reliable. In addition, this study aimed to determine whether the
assessment regarding the decision for operative treatment is affected by
evaluation of images on a mobile device as opposed to standard picture archiving
and communication system (PACS). METHODS: Standard anteroposterior and lateral
radiographs of 50 pediatric elbow trauma cases were evaluated by 2 fellowship
trained pediatric orthopaedic surgeons and 2 senior orthopaedic residents. Raters
were asked to classify the case as any of 6 diagnoses: supracondylar humerus,
lateral condyle, medial epicondyle, radial neck fracture, positive posterior fat
pad sign, or normal pediatric elbow. Raters were asked to choose operative or
conservative treatment. After 1 week, photographs of the same images were taken
from a standardized distance from a computer monitor with an iPhone 5 camera and
transmitted by multimedia messaging to each rater. The same questions were again
posed to raters. Interobserver and intraobserver reliabilities were calculated by
Cohen kappa-statistics with bootstrapped 95% confidence intervals. RESULTS:
Intraobserver reliability of classification of injuries on PACS compared with
smartphone images was excellent, with an overall kappa of 0.91. Treatment
decision also demonstrated excellent intraobserver reliability (PACS vs.
smartphones) with a kappa of 0.86 for all raters. CONCLUSIONS: Diagnosis of
pediatric elbow injuries can be made equally reliably based on either PACS or
transmitted multimedia messaging images taken with an iPhone camera from a
computer screen and viewed on a smartphone. Treatment decisions can also be made
reliably based on either image modality. CLINICAL RELEVANCE: Using smartphones to
transmit and display radiographs, which is common in current clinical practice,
is effective and reliable for diagnosis and treatment planning of pediatric elbow
injuries.
PMID- 25851689
TI - Doctor-to-doctor communication of prognosis in metastatic cancer: a review of
letters from medical oncologists to referring doctors.
AB - BACKGROUND: Shared understanding of prognosis is vital for optimal,
multidisciplinary, clinical decision making. AIMS: This study aims to determine
the frequency and nature of prognostic information in medical oncologists'
letters to referring doctors for patients with metastatic cancer. METHODS: We
reviewed all consultation letters (to June 2014) for new patients with metastatic
cancer presenting to medical oncologists at Concord and Macarthur Cancer Centres
between June 2012 and June 2013. We recorded the presence and nature of
prognostic information in the letters, patients' characteristics and survival.
Characteristics associated with inclusion of prognostic information were
explored. RESULTS: We analysed 1344 letters pertaining to 272 patients with a
median survival of 13 months. The median number of letters per patient was 4
(interquartile range 1-7), with 50% written by trainees. The terms 'metastatic'
or 'stage IV cancer' were included in letters for 253 patients (93%), treatment
was described as 'palliative' for 174 patients (64%) and the word 'incurable' was
included for 93 (34%). Only 31 patients (11%) had a quantitative estimate of
prognosis in any correspondence: median or average survival in 14, general time
frame in 12 and, best case, typical and worst case scenarios in 5. Inclusion of
quantitative prognostic information was not associated with patient age, cancer
type, treatment plan, trainee authoring letter or shorter survival. CONCLUSION:
Inclusion of quantitative prognostic information in written correspondence from
medical oncologists regarding patients with metastatic cancer was infrequent.
Encouraging oncologists to include quantitative prognostic information in their
letters could improve communication between oncologists, referring doctors and
patients.
PMID- 25851690
TI - Two Years of Cinacalcet Hydrochloride Treatment Decreased Parathyroid Gland
Volume and Serum Parathyroid Hormone Level in Hemodialysis Patients With Advanced
Secondary Hyperparathyroidism.
AB - The long-term effect of cinacalcet hydrochloride treatment on parathyroid gland
(PTG) volume has been scarcely investigated in patients with moderate to advanced
secondary hyperparathyroidism (SHPT). The present study was a prospective
observational study to determine the effect of cinacalcet treatment on PTG volume
and serum biochemical parameters in 60 patients with renal SHPT, already treated
with intravenous vitamin D receptor activator (VDRA). Measurement of biochemical
parameters and PTG volumes were performed periodically, which were analyzed by
stratification into tertiles across the baseline parathyroid hormone (PTH) level
or PTG volume. We also determined the factors that can estimate the changes in
PTG volume and the achievement of the target PTH range by multivariable analyses.
Two years of cinacalcet treatment significantly decreased the serum levels of
PTH, calcium, and phosphate, followed by the improvement of achieving the target
ranges for these parameters recommended by the Japanese Society for Dialysis
Therapy. Cinacalcet decreased the maximal and total PTG volume by about 30%, and
also decreased the serum PTH level independent of the baseline serum PTH level
and PTG volume. Ten out of 60 patients showed 30% increase in maximal PTG after 2
years. Multivariable analysis showed that patients with nodular PTG at baseline
and patients with higher serum calcium and PTH levels at 1 year were likely to
exceed the target range of PTH at two years. In conclusion, cinacalcet treatment
with intravenous VDRA therapy decreased both PTG volume and serum intact PTH
level, irrespective of the pretreatment PTG status and past treatment history.
PMID- 25851691
TI - Effect of lopinavir/ritonavir on the pharmacokinetics of selexipag an oral
prostacyclin receptor agonist and its active metabolite in healthy subjects.
AB - AIMS: This study investigated the effect of a fixed dose combination of
lopinavir/ritonavir on the pharmacokinetics (PK) of selexipag and its active
metabolite ACT-333679. METHODS: This was an open label, randomized, single
centre, two way, crossover study. Twenty healthy male subjects were treated with
a single dose of 400 ug selexipag alone and in combination with multiple doses of
lopinavir/ritonavir (400/100 mg) twice daily. RESULTS: The results showed that
lopinavir/ritonavir approximately doubled the exposure to selexipag. The area
under the plasma concentration-time curve from time zero to infinity
(AUC(0,infinity) and the maximum plasma concentration (Cmax) of selexipag were
2.2- and 2.1-fold higher, respectively, than under selexipag alone, with a 90%
confidence interval (CI) of the geometric mean ratio (GMR) of 1.9, 2.7 and 1.7,
2.6, respectively. For ACT-333679, the clinically more relevant component of
selexipag, systemic exposure was increased by 8% (GMR of AUC(0,infinity) 1.1, 90%
CI 0.9, 1.3), when lopinavir/ritonavir was co-administered with selexipag. The
most frequently reported adverse event (AE) was headache. A single dose of
selexipag, administered either alone or together with multiple doses of
lopinavir/ritonavir, was safe and well tolerated. CONCLUSIONS:
Lopinavir/ritonavir does not affect the PK parameters of selexipag and ACT-333679
to a clinically relevant extent. Therefore, adaptation of the selexipag dose is
not required when co-administered with inhibitors of the organic anion
transporting polypeptide (OATP) 1B1/ 1B3, P-glycoprotein (P-gp) and/or CYP3A4.
PMID- 25851692
TI - Transcriptional refractoriness is dependent on core promoter architecture.
AB - Genes are often transcribed in random bursts followed by long periods of
inactivity. Here we employ the light-activatable white collar complex (WCC) of
Neurospora to study the transcriptional bursting with a population approach.
Activation of WCC by a light pulse triggers a synchronized wave of transcription
from the frequency promoter followed by an extended period (~1 h) during which
the promoter is refractory towards restimulation. When challenged by a second
light pulse, the newly activated WCC binds to refractory promoters and has the
potential to recruit RNA polymerase II (Pol II). However, accumulation of Pol II
and phosphorylation of its C-terminal domain repeats at serine 5 are impaired.
Our results suggest that refractory promoters carry a physical memory of their
recent transcription history. Genome-wide analysis of light-induced transcription
suggests that refractoriness is rather widespread and a property of promoter
architecture.
PMID- 25851694
TI - Reviewing post-publication peer review.
AB - Post-publication peer review (PPPR) is transforming how the life sciences
community evaluates published manuscripts and data. Unsurprisingly, however, PPPR
is experiencing growing pains, and some elements of the process distinct from
standard pre-publication review remain controversial. I discuss the rapid
evolution of PPPR, its impact, and the challenges associated with it.
PMID- 25851695
TI - Detection of manipulations on printed images to address crime scene analysis: A
case study.
AB - Photographic documents both in digital and in printed format plays a fundamental
role in crime scene analysis. Photos are crucial to reconstruct what happened and
also to freeze the fact scenario with all the different present objects and
evidences. Consequently, it is immediate to comprehend the paramount importance
of the assessment of the authenticity of such images, to avoid that a possible
malicious counterfeiting leads to a wrong evaluation of the circumstance. In this
paper, a case study in which some printed photos, brought as documental evidences
of a familiar murder, had been fraudulently modified to bias the final judgement
is presented. In particular, the usage of CADET image forensic tool, to verify
printed photos integrity, is introduced and discussed.
PMID- 25851693
TI - Formation and activation of thermogenic fat.
AB - Thermogenic fat cells that convert chemical energy into heat are present in both
mice and humans. Recent years have witnessed great advances in our understanding
of the regulation of these adipocytes and an increased appreciation of the
potential these cells have to counteract obesity. We summarize recent efforts to
understand the formation of these fat cells and critically review genetic models
and other experimental tools currently available to further investigate the
development and activation of both classical brown and inducible beige fat cells.
We also discuss recent discoveries about the epigenetic regulation of these
adipocytes, and finally present emerging evidence revealing the metabolic impacts
of thermogenic fat in humans.
PMID- 25851696
TI - REPORT-HF: the unique blend of global heart failure registry and longitudinal
cohort study.
PMID- 25851697
TI - The relationship between serum 25(OH)D and bone density and microarchitecture as
measured by HR-pQCT.
AB - The relation between serum 25-hydroxy vitamin D [25(OH)D] and bone quality is not
well understood, particularly for high levels. We measured bone microarchitecture
in three groups of people stratified by their serum 25(OH)D. There was a weak
association of serum 25(OH)D and microarchitecture for this cross-sectional
population, suggesting possible benefits to bone quality. INTRODUCTION: Vitamin D
plays an important role in bone and mineral metabolism, but the relation between
serum 25(OH)D and bone quality is not well understood. Here, we present a cross
sectional study that investigated a convenience group of participants from an
ongoing health initiative in Alberta, Canada, who have been receiving daily
vitamin D supplementation. METHODS: A total of 105 participants were organized
into three groups based on their serum 25(OH)D levels: low (<75 nmol/L), medium
(75-175 nmol/L), and high (>175 nmol/L). They were also assessed with 25(OH)D as
a continuous variable. Average daily supplementation was 7670 +/- 438 IU, and the
change in 25(OH)D ranged from 22 to 33 % during the period of receiving
supplements. We used high-resolution peripheral quantitative computed tomography
measurements at the radius and tibia to assess bone microarchitecture. RESULTS:
Microarchitectural parameters were not strongly associated with serum 25(OH)D. In
the tibia, there were fewer trabeculae (TbN; p = 0.015) and a non-significant
trend toward thicker trabeculae (p = 0.067) of the high group. Body mass index
(BMI) was negatively associated with serum 25(OH)D levels (p < 0.001) and PTH
levels (p < 0.001). There was no clinically significant relationship detected
between high serum 25(OH)D and high serum calcium. CONCLUSION: These data suggest
a weak relationship between serum 25(OH)D and bone microarchitecture in this
population of mostly vitamin-D-sufficient participants, and there were no
indications of negative effects related to the high supplementation levels. These
data provided a basis to design and implement our 3-year dose-dependent
randomized controlled trial investigating the effects of vitamin D
supplementation on bone health outcomes.
PMID- 25851698
TI - A tuber calcanei avulsion fracture developed on the basis of idiopathic
osteoporosis in a young male: a case report.
AB - Calcaneus fractures constitute 1.2 % of all fractures. Tuber calcanei avulsion
fractures constitute 1.3-2.7 % of calcaneus fractures. Osteoporosis,
osteomalacia, and diabetes mellitus have been reported to increase the risk of
development of these fractures. It has been reported that tuber calcanei avulsion
fractures in elderly females might develop due to osteoporosis. As far as we
know, no tuber calcanei avulsion fracture developing on the basis of osteoporosis
without presence of a trauma has been reported in young males in the literature.
In the current case report, a 41-year-old male patient who was admitted with
complaints of pain in the left heel and diagnosed with calcaneal avulsion
fracture that developed on the basis of idiopathic osteoporosis and who was
treated with conservative methods was presented.
PMID- 25851699
TI - Prior ankle fractures in postmenopausal women are associated with low areal bone
mineral density and bone microstructure alterations.
AB - In a cross-sectional analysis in postmenopausal women, prior ankle fractures were
associated with lower areal bone mineral density (BMD) and trabecular bone
alterations compared to no fracture history. Compared to women with forearm
fractures, microstructure alterations were of lower magnitude. These data suggest
that ankle fractures are another manifestation of bone fragility. INTRODUCTION:
Whether ankle fractures represent fragility fractures associated with low areal
bone mineral density (aBMD) and volumetric bone mineral density (vBMD) and/or
bone microstructure alterations remains unclear, in contrast to the well
recognised association between forearm fractures and osteoporosis. The objective
of this study was to investigate aBMD, vBMD and bone microstructure in
postmenopausal women with prior ankle fracture in adulthood, compared with women
without prior fracture or with women with prior forearm fractures, considered as
typically of osteoporotic origin. METHODS: In a cross-sectional analysis in the
Geneva Retirees Cohort study, 63 women with ankle fracture and 59 with forearm
fracture were compared to 433 women without fracture (mean age, 65 +/- 1 years).
aBMD was measured by dual-energy X-ray absorptiometry; distal radius and tibia
vBMD and bone microstructure were measured by high-resolution peripheral
quantitative computed tomography. RESULTS: Compared with women without fracture,
those with ankle fractures had lower aBMD, radius vBMD (-7.9%), trabecular
density (-10.7%), number (-7.3%) and thickness (-4.6%) and higher trabecular
spacing (+14.5%) (P < 0.05 for all). Tibia trabecular variables were also
altered. For 1 standard deviation decrease in total hip aBMD or radius trabecular
density, odds ratios for ankle fractures were 2.2 and 1.6, respectively, vs 2.2
and 2.7 for forearm fracture, respectively (P <= 0.001 for all). Compared to
women with forearm fractures, those with ankle fractures had similar spine and
hip aBMD, but microstructure alterations of lower magnitude. CONCLUSION: Women
with ankle fractures have lower aBMD and vBMD and trabecular bone alterations,
suggesting that ankle fractures are another manifestation of bone fragility.
PMID- 25851701
TI - Ventricular Fibrillation due to Automated Atrial Threshold Testing in a Patient
with an Implantable Cardioverter Defibrillator.
PMID- 25851700
TI - Small molecule ice recrystallization inhibitors enable freezing of human red
blood cells with reduced glycerol concentrations.
AB - In North America, red blood cells (RBCs) are cryopreserved in a clinical setting
using high glycerol concentrations (40% w/v) with slow cooling rates (~1 degrees
C/min) prior to storage at -80 degrees C, while European protocols use reduced
glycerol concentrations with rapid freezing rates. After thawing and prior to
transfusion, glycerol must be removed to avoid intravascular hemolysis. This is a
time consuming process requiring specialized equipment. Small molecule ice
recrystallization inhibitors (IRIs) such as beta-PMP-Glc and beta-pBrPh-Glc have
the ability to prevent ice recrystallization, a process that contributes to
cellular injury and decreased cell viability after cryopreservation. Herein, we
report that addition of 110 mM beta-PMP-Glc or 30 mM beta-pBrPh-Glc to a 15%
glycerol solution increases post-thaw RBC integrity by 30-50% using slow cooling
rates and emphasize the potential of small molecule IRIs for the preservation of
cells.
PMID- 25851702
TI - Cost-Effectiveness of Long-Term Every Three-Year Versus Annual Postoperative
Surveillance for Low-Risk Papillary Thyroid Cancer.
AB - BACKGROUND: Patients with low-risk papillary thyroid cancer (PTC) who demonstrate
an excellent response to initial therapy have a 2% recurrence rate and 100%
disease-specific survival within 10 years. Thus, annual surveillance may be
excessive. We hypothesized that less frequent postoperative surveillance in these
patients is cost effective. METHODS: A Markov discrete time state transition
model was created to compare postoperative surveillance tapered to 3-year
intervals after 5 years of annual surveillance versus conventional annual
surveillance in low-risk PTC patients with negative neck ultrasound and
stimulated thyroglobulin less than 2 ng/mL 1 year postoperatively. Outcome
probabilities, utilities, and costs were determined via literature review, the
Medicare Physician Fee Schedule, and Healthcare Cost and Utilization Project
data. Sensitivity analyses were performed to assess areas of uncertainty.
RESULTS: The cost of annual surveillance was $5,239 per patient and yielded 22.49
quality-adjusted life-years (QALYs). The 3-year strategy cost $2,601 less, but
also yielded 0.01 less QALYs. Thus, the incremental cost per QALY of annual
surveillance was $260,100. Probabilistic sensitivity analysis demonstrated that
less frequent surveillance was more cost effective in 99.98% of 10,000 simulated
patients. One-way sensitivity analysis revealed that annual surveillance would be
cost effective if the total cost of neck ultrasound could be reduced to $23 or
less. CONCLUSION: Extending postoperative surveillance to 3-year intervals after
5 years of annual surveillance in patients with low-risk PTC with excellent
response to therapy is more cost effective than annual surveillance.
PMID- 25851703
TI - Role of Apoptosis in the Development of Uterine Leiomyoma: Analysis of Expression
Patterns of Bcl-2 and Bax in Human Leiomyoma Tissue With Clinical Correlations.
AB - To describe gene expression patterns of the apoptotic regulatory genes Bcl and
Bax in human uterine leiomyoma tissue. To investigate the relationship between
alterations of gene expression patterns and several relevant clinical parameters.
We obtained samples from 101 cases undergoing surgery for uterine leiomyoma for
gene expression analysis of the Bcl-2 and Bax genes. Gene expression was
quantified using RT-PCR technique. In the leiomyoma group, the Bcl-2 gene was
significantly overexpressed compared with the control group although there was no
such difference in the gene expression of Bax. Gene activity of Bcl-2 positively
correlated with the tumor number in individual uterine leiomyoma cases. Although
there was no significant correlation between the length of the cumulative
lactation period before the development of uterine leiomyoma and Bcl-2 gene
expression in the leiomyoma tissue, we observed a trend for a shorter cumulative
lactation period to be associated with overexpression of the Bcl-2 gene.
Overexpression of the antiapoptotic Bcl-2 gene appeared to be a factor in the
development of uterine leiomyoma, whereas gene activity of the proapoptotic Bax
gene did not seem to play a role in the process.
PMID- 25851704
TI - Endometrial Carcinomas With Clear Cells: A Study of a Heterogeneous Group of
Tumors Including Interobserver Variability, Mutation Analysis, and
Immunohistochemistry With HNF-1beta.
AB - Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a
poor prognosis. It has histologic features that overlap with other endometrial
carcinomas and is frequently misclassified. Accurate classification is crucial,
however, to improve treatment options. The objectives of this study were (1) to
assess diagnostic interobserver variability among 5 gynecologic pathologists for
tumors originally diagnosed as CC or with a component of CC (n=44); (2) to
determine the utility of immunohistochemical markers estrogen receptor and HNF
1beta; and (3) to detect mutations in select genes. Clinical data and morphologic
features were also recorded. Agreement among reviewers was only moderate: only
46% of the original CC remained classified as such. After reclassification,
estrogen receptor was positive in 8% of CC, 67% of endometrioid carcinomas (EC),
and 47% of serous carcinomas (SC). Sensitivities of HNF-1beta in CC, SC, and EC
were 62%, 27%, and 17%, respectively, whereas specificity for CC versus EC or SC
was 78%. Mutations in PIK3CA, PIK3R1, PTEN, KRAS, and NRAS were detected in 41%
of 37 cases that had adequate material for study. At least 1 mutation was
identified in 33% of CC, 67% of EC, and 33% of SC. This group of patients had
poor outcomes: 72% of the patients with follow-up information had died of
disease. In summary, this study suggests that the current pool of CC is a
heterogeneous group of tumors from the morphologic, immunophenotypic, and
molecular point of views and that only a percentage of them represent true CC.
PMID- 25851705
TI - Giant Cell Tumor of the Uterus: A Report of 3 Cases With a Spectrum of
Morphologic Features.
AB - Giant cell tumors, a well-recognized neoplasm of bone, can rarely be found in the
uterus. Such tumors are characterized by a dual population of mononuclear and
osteoclast-like giant cells that lack epithelial and specific mesenchymal
differentiation. In this study, the clinicopathologic features of 3 giant cell
tumors of the uterus were reviewed. Immunohistochemistry for CD68, CD163, h
caldesmon, desmin, SMA, AE1/AE3, CD10, ER, PR, cyclin D1, CD1a, CD34, CD30, S100,
myogenin/myoglobin, and Ki-67 was performed in all tumors, along with
ultrastructural analysis in one. The patients were 47, 57, and 59 yr and the
tumors measured 2.5, 7.5, and 16.0 cm. One neoplasm was confined to the
endometrium, whereas the other 2 were myometrial. All 3 tumors showed a nodular
growth comprised of mononuclear and osteoclast-like giant cells. The endometrial
confined tumor consisted of histologically benign mononuclear cells, whereas the
others exhibited marked atypia. Mitotic activity was up to 5/10 HPF in the benign
tumor and up to 22/10 HPF in the malignant. No cytologic atypia or mitoses were
observed in the giant cells. CD68 and CD10 were strongly and diffusely expressed
in both components of 3 and 2 neoplasms, respectively. Cyclin D1 was focal in the
mononuclear cells and focal to diffuse in the giant cells. CD163 was diffuse in
the mononuclear cells, but absent to focal in the giant cells. Ultrastructural
analysis lacked diagnostic features of epithelial or specific mesenchymal
differentiation. Both malignant tumors demonstrated an aggressive behavior. In
summary, although rare, giant cell tumor of the uterus should be included in the
differential diagnosis of benign or malignant tumors containing osteoclast-like
giant cells.
PMID- 25851706
TI - Sclerosing Stromal Tumors With Prominent Luteinization During Pregnancy: A Report
of 8 Cases Emphasizing Diagnostic Problems.
AB - Ovarian tumors encountered during pregnancy can pose a diagnostic challenge due
to an abundance of luteinized cells and other changes. We report 8 sclerosing
stromal tumors with massive luteinization discovered in pregnant patients. The
tumors ranged from 3.1 to 21 cm (mean=8.8 cm) in size and were typically solid
and yellow; the neoplasm was bilateral in 1 case. On microscopic examination, the
lutein cells, a feature of sclerosing stromal tumor, had more copious
eosinophilic cytoplasm and were more numerous than is usually seen in nonpregnant
patients and to varying degrees obscured the typical pseudolobular pattern. This
resulted in particular diagnostic difficulty in 3 cases, especially when
associated with other changes including irregular shapes of tumor cell nests,
edema, and/or myxoid change. However, classic features of these tumors: ectatic
vessels and admixed luteinized and nonluteinized cells were still focally
evident, allowing for accurate classification. The tumors were cytologically
bland and with 1 exception had rare mitoses. As sclerosing stromal tumors have
been invariably benign, it is important that they not be confused with other
tumors, such as steroid cell tumor, which can occasionally be malignant.
PMID- 25851707
TI - Placental Molar Disease: What are the Benefits and Barriers to the Adoption of a
Comprehensive Diagnostic Service?
AB - The molecular cytogenetic analysis of specimens (genotyping) suspicious for
hydatidiform mole (HM) significantly improves diagnostic accuracy over
histopathology and immunohistochemical analysis alone, particularly in the
classification of partial mole. However, the implementation of this advance in
diagnostics has been slow. This study sought to identify the major benefit and
potential barriers to the adoption of genotyping. A pilot Placental Molar
Diagnostic (PMD) Service was established combining histopathology, p57
immunohistochemistry, and molecular genotyping analysis for both in-house and
referred-in cases suspicious for HM or with a preliminary diagnosis of HM. A
retrospective analysis of 117 cases received in the first 16 mo was conducted to
identify the utility of the PMD Service and factors or barriers which precluded
optimal results. A final diagnosis of HM was made in 73 cases (37 complete HMs
and 36 partial HMs). The remaining 44 cases were hydropic abortuses. Three
potential barriers were identified that could lead to less than optimal results
from a PMD Service: prevalence of noninformative genotyping, lack of any
available or appropriate paraffin blocks, and inappropriate deferral of
genotyping. The major utility of this pilot PMD Service was to increase the
specificity of a diagnosis of HM, and avoid unnecessary clinical follow-up in 37%
of cases with an initial suspicion or diagnosis of HM. Measures can be undertaken
to address potential barriers to the implementation of a comprehensive placental
diagnostic platform. Underutilization of molecular genotyping in the diagnosis of
HM likely leads to inappropriate management and "downstream" costs in a
significant proportion of patients suspected of having HM.
PMID- 25851708
TI - A Case of Vulval Extramammary Paget Disease With Dermal Invasion Showing Mucinous
Carcinoma.
AB - We report a case of vulval extramammary Paget disease (EMPD) with dermal invasion
showing mucinous carcinoma (MC). An 80-year-old woman presented with vulvar
itching and pain. A physical examination showed a pigmented vulvar, perianal
erythematous plague, and a subcutaneous nodule in the left major labia. No
internal malignancy, such as colorectal or genitourinary carcinoma, was
identified in any of the clinical examinations. A histological examination of the
resected specimen revealed Pagetoid tumor cells that had spread widely through
the epidermis and invaded the dermis forming a solid nest with mucous lake-like
MC. Immunohistochemical examination revealed that the tumor cells in the
epidermis and dermis were positive for CK7, CEA, GCDFP-15, MUC5AC, and MUC2, but
negative for CK20, MUC6, and CDX2. Only the invasive component showed
overexpression of p53. A diagnosis of primary EMPD with dermal invasion showing
MC of the vulva was made. This is an extremely rare diagnosis, and we suggest
that immunohistochemical evaluations in addition to systemic work-ups are helpful
in distinguishing between these cases and those involving vulvar or perianal skin
invasion of underlying colorectal or genitourinary carcinomas, which are referred
to as secondary EMPD.
PMID- 25851709
TI - Ovarian Hemangiomas Do Not Harbor EWSR1 Rearrangements: Clinicopathologic
Characterization of 10 Cases.
AB - Hemangiomas of the ovary are rare with a majority described as individual reports
of unusual clinical presentations or morphologic findings. Both the expected and
unexpected pathologic features of these tumors in the ovary are not well
detailed. Therefore, we collected the largest series of ovarian hemangiomas to
comprehensively define their clinicopathologic associations and examine the
significance of hormone receptors in their pathogenesis. In addition, a novel
EWSR1-NFATC1 fusion has recently been described in a case of hemangioma of bone.
To our knowledge, EWSR1 rearrangement has not been evaluated in hemangiomas of
other sites or in a case series. Accordingly, we used fluorescence in situ
hybridization to investigate EWSR1 status in a majority of our cases. Clinical
presentation was variable and dependent on tumor size. Patient age ranged 48 to
87 yr (median 63 yr). Tumors involved the right (n=6) and left (n=3) ovaries with
laterality unknown in 1 case, and size ranged from 0.2 to 5.0 cm (median 1.0 cm).
Three of 4 radiologic reports were either equivocal or could not exclude
malignancy. Seven cases were of the cavernous type and 3 were mixed cavernous and
capillary type. All lesions formed a single discrete, circumscribed mass that
displaced the surrounding cortical stroma. The cavernous type showed dilated,
thin-walled vessels and vascular thrombi, some of which were associated with
dystrophic calcification. In addition to cavernous morphology, the mixed form
exhibited features of capillary hemangioma such as lobulated growth of capillary
sized vascular spaces that lacked atypia or multilayering and were linked to a
larger feeding vessel. Each tumor expressed CD31, CD34, FLI-1, ERG, but not D240.
The hemangioma stromal cells, but not endothelium, expressed estrogen and
progesterone receptors in every case. Stromal luteinization was seen in 2 cases.
Follow-up ranged 1 to 139 mo and all patients were disease free. All cases were
negative for EWSR1 rearrangement; however, 2 cases demonstrated additional intact
copies of EWSR1 indicating aneusomy 22 or a structural abnormality of chromosome
22 resulting in apparent duplication of the EWSR1 gene region (at 22q12).
Although an uncommon entity, awareness of ovarian hemangioma's unique and diverse
clinical presentation as well as its potential to radiologically imitate
malignant ovarian neoplasms are important.
PMID- 25851710
TI - "Pseudomyxoma Endometrii": Endometrial Deposition of Acellular Mucin from a Low
Grade Appendiceal Mucinous Neoplasm as a Rare Mimic of Myxoid Uterine Tumors.
AB - Low-grade appendiceal mucinous neoplasms (LAMNs) are commonly associated with
deposition of mucin, with or without admixed low-grade epithelium, on peritoneal
surfaces (pseudomyxoma peritonei). We describe a very rare presentation of LAMN
as extensive mucin deposition in the endometrium of a 43-yr-old woman initially
mistaken for a primary uterine myxoid neoplasm. The patient underwent endometrial
curettage that demonstrated abundant myxoid/mucoid material interspersed with
small vessels, bland eosinophilic spindled cells, scattered foci of typical
endometrial stroma, and occasional endometrioid glands. The endometrial stroma
was positive for CD10, and the eosinophilic spindled cells were positive for
actin. The lesion was interpreted as "myxoid/mucinous neoplasm, most likely of
smooth muscle/endometrial stromal origin." Subsequent laparotomy revealed
peritoneal mucin in the anterior cul-de-sac and a dilated appendix. Pathologic
review confirmed appendiceal LAMN and multifocal peritoneal mucinosis. The uterus
contained scant residual mucoid material. On review of all pathologic material at
our institution, the endometrial lesion was consistent with organizing mucin
derived from the LAMN with entrapped benign endometrium. "Pseudomyxoma
endometrii" is readily mistaken for a primary uterine myxoid neoplasm,
particularly myxoid endometrial stromal tumor. A key to diagnosis is recognition
that the material is mucin rather than myxoid stroma. This is evidenced by the
absence of embedded stromal cells and presence of myofibroblastic, vascular, and
macrophage infiltration associated with organization. Epithelium containing
goblet cells is an important clue if present. The presence of rare endometrial
glands within the endometrial stroma suggests that the latter is entrapped rather
than neoplastic.
PMID- 25851711
TI - Differential Expression Patterns of GATA3 in Uterine Mesonephric and
Nonmesonephric Lesions.
AB - GATA binding protein 3 (GATA3) is a recently described immunohistochemical marker
that has proven useful in the characterization of breast and urothelial
carcinomas. However, the expression pattern of GATA3 in mesonephric
proliferations is largely unknown. The aim of this study was to examine the
immunohistochemical expression of GATA3 in cervicovaginal mesonephric lesions and
compare it to its expression in endocervical and endometrial adenocarcinomas and
cervicovaginal endometriosis. A cohort of 107 cases, including 33 cases of
mesonephric lesions and 74 cases of nonmesonephric lesions, was selected for the
study. Of 33 mesonephric lesions, 31 (94%) cases (16 remnants, 12 hyperplasias,
and 3 adenocarcinomas) were strongly and diffusely positive in tumor cell nuclei
for GATA3. The remaining 2 mesonephric carcinosarcomas showed focal nuclear
staining and rare nuclear positivity, respectively. Of 36 endocervical
adenocarcinomas, 33 (92%) were negative for GATA3 and the remaining revealed
focal weak nuclear staining. Of 34 endometrial adenocarcinomas, 32 (94%) were
negative, whereas 2 showed rare nuclear positivity. All 4 cases of endometriosis
were negative. The benign endocervical epithelium and the benign endometrium in
most cases lacked GATA3 expression, whereas the benign squamous epithelium in the
majority exhibited nuclear basal and parabasal staining pattern. Our study
demonstrates that GATA3 protein is expressed in most mesonephric lesions,
regardless of them being benign or malignant. In contrast, GATA3 is absent in the
majority of endometrial and endocervical adenocarcinomas. These results support
that GATA3 immunostain can be a useful tool in differentiating mesonephric
lesions from endocervical and endometrial adenocarcinomas.
PMID- 25851712
TI - Vulvar Myxoid Liposarcoma and Well Differentiated Liposarcoma With Molecular
Cytogenetic Confirmation: Case Reports With Review of Malignant Lipomatous Tumors
of the Vulva.
AB - Malignant lipomatous tumors of the vulva are uncommon. We present 2 cases of
liposarcoma arising in the vulva: a myxoid liposarcoma harboring DDIT3 and FUS
rearrangements and a well differentiated liposarcoma/atypical lipomatous tumor
harboring MDM2 amplification detected by fluorescence in situ hybridization. Both
cases are the first liposarcomas of this site to be confirmed by molecular
cytogenetic analysis. We also review the literature's cases of liposarcoma to
further examine the clinicopathologic features of these tumors.
PMID- 25851713
TI - Defective DNA Mismatch Repair Influences Expression of Endometrial Carcinoma
Biomarkers.
AB - Endometrial endometrioid carcinomas are related to estrogen excess and express
estrogen and progesterone receptors. However, hormone receptor expression can be
variable from tumor to tumor, and this variability is not always explained by
differences in tumor grade. Variable expression of other biomarkers that may be
used in the diagnostic work-up of endometrial cancer has also been noted. We
hypothesized that mismatch repair (MMR) defects may contribute to this
variability. A total of 411 unselected endometrial carcinomas were evaluated for
immunohistochemical expression of DNA MMR proteins and MLH1 methylation. Loss of
immunohistochemical expression of MLH1, MSH2, MSH6, or PMS2 was defined as MMR
deficient; positive expression was defined as MMR intact. A case-control cohort
of 80 Grade 2 endometrioid carcinomas was selected from this set (40 MMR
deficient, 40 MMR intact). Cases were matched for histotype, grade, and age.
Estrogen receptor, progesterone receptor, CK7(+), CK20, and Pax-8
immunohistochemistry was evaluated. The median percentage of CK7 tumor cells was
significantly lower in the MMR deficient group compared with the MMR intact
group. The mean percentage of tumor cells exhibiting estrogen receptor expression
was similar in both the MMR-deficient and MMR intact groups. However, there was
greater variability in the MMR-deficient group. Our study shows that MMR defects
influence the expression of clinically important biomarkers for endometrioid-type
endometrial carcinoma as decreased cytokeratin 7 expression is more commonly
associated with MMR deficiency.
PMID- 25851714
TI - Identifying palliative care issues in inpatients dying following stroke.
AB - BACKGROUND: Stroke leads to high mortality and morbidity but often there is a
conflict between need for palliative care and avoidance of 'therapeutic
nihilism'. AIMS: We aimed to elicit the palliative care needs of stroke patients
at the end of their lives in our unit with a low overall mortality rate (1 month:
8.8 %, inpatient: 12.9 %). METHODS: We identified consecutive stroke patients who
died over 2 years. Their clinical records were used for data collection. RESULTS:
Of 54 deaths, 33 (61.1 %) were females, mean (SD) age at death was 79.3 +/- 12.9
years. 41 (75.9 %) died after first stroke, 9 (16.7 %) were inpatient strokes, 7
(13.0 %) thrombolysed and 7 (13.0 %) had strokes as treatment complication. There
were clear statements recorded in 26 (48.1 %) that patients were dying and death
was thought to be due primarily to extent of brain injury in 24 (44.4 %).
Palliative needs identified included dyspnoea 21 (38.9 %), pain 17 (31.5 %),
respiratory secretions 17 (31.5 %), agitation 14 (25.9 %) and psychological
distress 1 (1.9 %). Symptoms were due to premorbid diseases in 6 (11.1 %).
Palliative care expertise were sought in 13 (24.1 %) and continuous subcutaneous
infusion was used in 18 (33.3 %) to control symptoms. 4 (7.4 %) subjects
underwent cardiac arrest calls and 9 (16.7 %) deaths occurred in ICU/HDU. The
median Stroke-Death interval was 20 days (range 0-389). Do Not Attempt
Resuscitation (DNAR) orders were in place in 86.8 % of patients. The median DNAR
Death interval was 7 days (range 0-311) with 7-day DNAR-Death rate of 53.2 % and
30-day of 78.7 % of the total deaths. CONCLUSIONS: Dyspnoea, pain and respiratory
secretions were identified as the main palliative care needs.
PMID- 25851716
TI - Stepwise optimization of a low-temperature Bacillus subtilis expression system
for "difficult to express" proteins.
AB - In order to improve the overproduction of "difficult to express" proteins, a low
temperature expression system for Bacillus subtilis based on the cold-inducible
promoter of the desaturase-encoding des gene was constructed. Selected regulatory
DNA sequence elements from B. subtilis genes known to be cold-inducible were
fused to different model genes. It could be demonstrated that these regulatory
elements are able to mediate increased heterologous gene expression, either by
improved translation efficiency or by higher messenger RNA (mRNA) stability. In
case of a cold-adapted beta-galactosidase from Pseudoalteromonas haloplanktis
TAE79A serving as the model, significantly higher expression was achieved by
fusing its coding sequence to the so-called "downstream box" sequence of cspB
encoding the major B. subtilis cold-shock protein. The combination of this fusion
with a cspB 5'-UTR stem-loop structure resulted in further enhancement of the
beta-galactosidase expression. In addition, integration of the transcription
terminator of the B. subtilis cold-inducible bkd operon downstream of the target
genes caused a higher mRNA stability and enabled thus a further significant
increase in expression. Finally, the fully optimized expression system was
validated by overproducing a B. subtilis xylanase as well as an alpha-glucosidase
from Saccharomyces cerevisiae, the latter known for tending to form inclusion
bodies. These analyses verified the applicability of the engineered expression
system for extracellular and intracellular protein synthesis in B. subtilis,
thereby confirming the suitability of this host organism for the overproduction
of critical, poorly soluble proteins.
PMID- 25851717
TI - Reconstruction of the carnitine biosynthesis pathway from Neurospora crassa in
the yeast Saccharomyces cerevisiae.
AB - Industrial synthesis of L-carnitine is currently performed by whole-cell
biotransformation of industrial waste products, mostly D-carnitine and
cronobetaine, through specific bacterial species. No comparable system has been
established using eukaryotic microorganisms, even though there is a significant
and growing international demand for either the pure compound or carnitine
enriched consumables. In eukaryotes, including the fungus Neurospora crassa, L
carnitine is biosynthesized through a four-step metabolic conversion of
trimethyllysine to L-carnitine. In contrast, the industrial yeast, Saccharomyces
cerevisiae lacks the enzymes of the eukaryotic biosynthesis pathway and is unable
to synthesize carnitine. This study describes the cloning of all four of the N.
crassa carnitine biosynthesis genes and the reconstruction of the entire pathway
in S. cerevisiae. The engineered yeast strains were able to catalyze the
synthesis of L-carnitine, which was quantified using hydrophilic interaction
liquid chromatography electrospray ionization mass spectrometry (HILIC-ESI-MS)
analyses, from trimethyllysine. Furthermore, the yeast threonine aldolase Gly1p
was shown to effectively catalyze the second step of the pathway, fulfilling the
role of a serine hydroxymethyltransferase. The analyses also identified yeast
enzymes that interact with the introduced pathway, including Can1p, which was
identified as the yeast transporter for trimethyllysine, and the two yeast serine
hydroxymethyltransferases, Shm1p and Shm2p. Together, this study opens the
possibility of using an engineered, carnitine-producing yeast in various
industrial applications while providing insight into possible future strategies
aimed at tailoring the production capacity of such strains.
PMID- 25851715
TI - Enhanced C30 carotenoid production in Bacillus subtilis by systematic
overexpression of MEP pathway genes.
AB - Creating novel biosynthetic pathways and modulating the synthesis of important
compounds are one of the hallmarks of synthetic biology. Understanding the key
parameters controlling the flux of chemicals throughout a metabolic pathway is
one of the challenges ahead. Isoprenoids are the most functionally and
structurally diverse group of natural products from which numerous medicines and
relevant fine chemicals are derived. The well-characterized and broadly used
production organism Bacillus subtilis forms an ideal background for creating and
studying novel synthetic routes. In comparison to other bacteria, B. subtilis
emits the volatile compound isoprene, the smallest representative of isoprenoids,
in high concentrations and thus represents an interesting starting point for an
isoprenoid cell factory. In this study, the effect of systematic overexpression
of the genes involved in the methylerythritol phosphate (MEP) pathway on
isoprenoid production in B. subtilis was investigated. B. subtilis strains
harboring a plasmid containing C30 carotenoid synthetic genes, crtM and crtN,
were combined with pHCMC04G plasmids carrying various synthetic operons of the
MEP pathway genes. The levels of produced carotenoids, diaponeurosporene and
diapolycopene, were used as indication of the role of the various enzymes on the
flux of the MEP pathway. It was shown that the production of carotenoids can be
increased significantly by overexpressing the MEP pathway enzymes. More broadly,
the strains developed in this study can be used as a starting point for various
isoprenoid cell factories.
PMID- 25851718
TI - Metabolic engineering of Clostridium tyrobutyricum for n-butanol production:
effects of CoA transferase.
AB - The overexpression of CoA transferase (ctfAB), which catalyzes the reaction:
acetate/butyrate + acetoacetyl-CoA -> acetyl/butyryl-CoA + acetoacetate, was
studied for its effects on acid reassimilation and butanol biosynthesis in
Clostridium tyrobutyricum (Deltaack, adhE2). The plasmid pMTL007 was used to co
express adhE2 and ctfAB from Clostridium acetobutylicum ATCC 824. In addition,
the sol operon containing ctfAB, adc (acetoacetate decarboxylase), and ald
(aldehyde dehydrogenase) was also cloned from Clostridium beijerinckii NCIMB 8052
and expressed in C. tyrobutyricum (Deltaack, adhE2). Mutants expressing these
genes were evaluated for their ability to produce butanol from glucose in batch
fermentations at pH 5.0 and 6.0. Compared to C. tyrobutyricum (Deltaack, adhE2)
without expressing ctfAB, all mutants with ctfAB overexpression produced more
butanol, with butanol yield increased to 0.22 - 0.26 g/g (vs. 0.10 - 0.13 g/g)
and productivity to 0.35 g/l h (vs. 0.13 g/l h) because of the reduced acetate
and butyrate production. The expression of ctfAB also resulted in acetone
production from acetoacetate through a non-enzymatic decarboxylation.
PMID- 25851719
TI - Characterization of a bioflocculant from potato starch wastewater and its
application in sludge dewatering.
AB - A bioflocculant was produced by using potato starch wastewater; its potential in
sludge dewatering and potato starch wastewater treatment was investigated.
Production of this bioflocculant was positively associated with cell growth, and
a highest value of 0.81 g/L was obtained. When incubated with this bioflocculant,
dry solids (DS) and specific resistance to filtration (SRF) of typical wastewater
activated sludge reached 20.8% and 3.9 * 10(12) m/kg, respectively, which were
much better than the ones obtained with conventional chemical flocculants. Sludge
dewatering was further improved when both the bioflocculant and conventional
polyacrylamide (PAM) were used simultaneously. With potato starch wastewater,
chemical oxygen demand (COD) and turbidity removal rates could reach 52.4 and
81.7%, respectively, at pH value of 7.5 when the bioflocculant dose was adjusted
to 30 mg/L; from a practical standpoint, the removal of COD and turbidity reached
48.3 and 72.5%, respectively, without pH value adjustment.
PMID- 25851720
TI - The British Society for Haematology: 'What have the Romans ever done for us?'.
AB - '....Alright, but apart from the sanitation, medicine, education, wine, public
order, irrigation, the roads, fresh water and public health..................what
have the Romans ever done for us?' From Monty Python's Life of Brian An
organizational review of the British Society for Haematology (BSH) was started in
November 2013 and completed in June 2014. Many members of the Society
participated in the surveys and have given their views, including those on the
Shape of Training Greenaway report. Members' views were incorporated in the
review and these have informed the eight strategic aims agreed at the Board
meeting on 10 June 2014. The BSH will aim to realise these strategic aims over
the next three to five years.
PMID- 25851722
TI - Correlation between the molecular structure and the kinetics of decomposition of
azamacrocyclic copper(ii) complexes.
AB - The formation of copper(ii) complexes with symmetrical dinucleating macrocyclic
ligands containing two either monomethylated () or trimethylated ()
diethylenetriamine (Medien or Me3dien) subunits linked by pyridine spacers has
been studied by potentiometry. Potentiometric studies show that has larger
basicity than as well as higher stability of its mono- and binuclear complexes.
The crystal structures of .6HCl (), [Cu2(L1)Cl2](CF3SO3)2 (),
[Cu2(L1)(OH)](ClO4)3.3H2O () and [Cu(L1)](ClO4)2 () show that adopts different
coordination modes when bound to copper(ii). Whereas in , each copper(ii) is
bound to one Medien subunit and to one pyridine group, in each metal center is
coordinated to one 2,6-di(aminomethyl)pyridine moiety (damp) and to one
aminomethyl group. The mononuclear complex shows pseudo-octahedral coordination
with two weakly coordinated axial nitrogens. Kinetic studies indicate that
complex decomposition is strongly dependent on the coordination mode of . Upon
addition of an acid excess, all the species except [Cu2(L1)](4+) convert very
rapidly to an intermediate that decomposes more slowly to copper(ii) and a
protonated ligand. In contrast, [Cu2(L1)](4+) decomposes directly without the
formation of any detectable intermediate. These results can be rationalized by
considering that the crystal structures are maintained in solution and that the
weakest Cu-N bonds are broken first, thus indicating that kinetic measurements on
complex decomposition can be used to provide information about structural
reorganizations in the complexes. In any case, complete decomposition of the
complexes takes place in a maximum of two kinetically resolvable steps. However,
minor changes in the structure of the complexes can lead to drastic changes in
the kinetics of decomposition and the complexes decompose with polyphasic
kinetics in which up to four different steps associated with the successive
breaking of the different Cu-N bonds can be resolved.
PMID- 25851721
TI - Impact of medical education program on COPD patients: a cohort prospective study.
AB - BACKGROUND: The main objective of this study was to assess the effects of
intensive medical education courses on chronic obstructive pulmonary disease
(COPD)-related rehospitalizations and emergency department visits and the
secondary aim was to monitor quality of life. METHODS: This cohort prospective
study included 76 group D COPD patients (pts.). Patients from the intervention
group (IG, 52 pts.) underwent a program comprising two components: a
comprehensive medical education program (1h/day for 5 days) and a specific drug
therapy. Control group (CG, 24 pts.) received only drug therapy. Patients
underwent spirometry and completed St. George's Respiratory Questionnaire (SGRQ)
at the time of inclusion and at periodical evaluations performed every three
months for a year. RESULTS: Patients included in a medical education program
showed significant decrease of exacerbation rate compared with the CG. Patients
from the IG group had fewer emergency department visits within a year compared
with the CG. Patients from the IG had significantly better quality of life scores
(both at 3 and 6 months) compared with the CG. CONCLUSIONS: This study reveals
that an adequate medical education program is associated with a decreased rate of
COPD-related hospitalizations. The implementation of a medical education program
as an integrated part of therapy could lead to a more accurate self-management of
the disease.
PMID- 25851723
TI - JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family.
AB - Recently autosomal recessively inherited mutations in the gene encoding Jagunal
homolog 1 (JAGN1) was described as a novel disease-causing gene of severe
congenital neutropenia (SCN) JAGN1-mutant neutrophils were characterized by
abnormality in endoplasmic reticulum structure, absence of granules, abnormal N
glycosylation of proteins and susceptibility to apoptosis. These findings imply
the role of JAGN1 in neutrophil survival. Here, we report two siblings with a
homozygous mutation in JAGN1 gene, exhibiting multisystemic involvement.
PMID- 25851725
TI - Diversity and antifungal activity of the endophytic fungi associated with the
native medicinal cactus Opuntia humifusa (Cactaceae) from the United States.
AB - The endophytic fungal community associated with the native cactus Opuntia
humifusa in the United States was investigated and its potential for providing
antifungal compounds. A hundred-eight endophytic fungal isolates were obtained
and identified by molecular methods into 17 different taxa of the genera
Alternaria, Aureobasidium, Biscogniauxia, Cladosporium, Cryptococcus, Curvularia,
Diaporthe, Epicoccum, Paraconiothyrium, Pestalotiopsis and Phoma. The most
frequent species associated with O. humifusa were Alternaria sp. 3, Aureobasidium
pullulans and Diaporthe sp. The fungal community of O. humifusa had a high
richness and diversity; additionally, the species richness obtained indicates
that the sample effort was enough to recover the diversity pattern obtained. Six
extracts of endophytes showed antifungal properties and (1)H NMR analyses of the
extracts of Alternaria sp. 5 Ohu 8B2, Alternaria sp. 3 Ohu 30A, Cladosporium
funiculosum Ohu 17C1 and Paraconiothyrium sp. Ohu 17A indicated the presence of
functional groups associated with unsaturated fatty-acid olefinic protons and
fatty acid methylene and methyl protons. GC-FID analysis of these extracts
confirmed the presence of a mixture of different fatty acids. The (1)H NMR
analyses of Biscogniauxia mediterranea Ohu 19B extracts showed the presence of
aromatic compounds. From the extract of B. mediterranea we isolated the compound
5-methylmellein that displayed moderate antifungal activity against the
phytopathogenic fungi Phomopsis obscurans. Our results suggest that native
medicinal cacti of the United States can live symbiotically with rich and diverse
endophytic communities and may be a source of bioactive molecules, including
those able to inhibit or control plant disease pathogens.
PMID- 25851726
TI - Alterations in the expression of genes related to contractile function and
hypertrophy of the left ventricle in chronically paced patients from the right
ventricular apex.
AB - AIM: Long-term right ventricular apical (RVA) pacing may lead to left ventricular
(LV) remodelling and heart failure. This study assessed changes in the expression
of genes regulating LV contractile function and hypertrophy, after permanent RVA
pacing and investigated whether such changes proceed or even predict LV
remodelling. METHODS AND RESULTS: We enrolled 52 consecutive patients (age 79.1
+/- 7.7 years, 34 males) who underwent pacemaker implantation for bradycardic
indications: Group A, 24 individuals with atrioventricular conduction
disturbances and group B, 28 patients with sinus node disease. In group A,
peripheral blood mRNA levels of gene sarcoplasmic reticulum calcium ATPase
decreased at 3, 6, and 12 months' follow-up, while alpha-myosin heavy chain (MHC)
decreased and beta-MHC increased until 6 months follow-up. In this group, 25% of
patients demonstrated significant LV remodelling. At 4 years, LV end-systolic
diameter increased from 29.67 +/- 3.39 mm at baseline to 35.38 +/- 4.22 mm, LV
end-diastolic diameter increased from 50 +/- 4.95 to 56.71 +/- 5.52 mm, and
ejection fraction declined from 63.04 +/- 10.22 to 52.83 +/- 10.81%. Early
alterations in gene expression were associated with a deterioration in LV
function and geometry that became apparent months later. In group B,
echocardiographic indexes and mRNA levels of the evaluated genes demonstrated no
statistically significant changes. CONCLUSIONS: Permanent RVA pacing in patients
with preserved ejection fraction is associated with alterations in the expression
of genes regulating LV contractile function and hypertrophy, measured in the
peripheral blood. These alterations are traceable at an early stage, before
echocardiographic changes are apparent and are associated with LV remodelling
that becomes evident in the long term.
PMID- 25851727
TI - Why Accurate Knowledge of Zygosity is Important to Twins.
AB - All same-sex dizygotic (DZ) twins and approximately one-third of monozygotic (MZ)
twin pairs have separate placentas, making it impossible to use the number of
placentas to determine zygosity. Zygosity determination is further complicated
because incorrect assumptions are often made, such as that only DZ pairs have two
placentas and that all MZ pairs are phenotypically identical. These assumptions,
by twins, their families and health professionals, along with the lack of
universal zygosity testing for same-sex twins, has led to confusion within the
twin community, yet little research has been conducted with twins about their
understanding and assumptions about zygosity. We aimed to explore and quantify
understanding and assumptions about zygosity using twins attending an Australian
twin festival. We recruited 91 twin pairs younger than 18 years of age and their
parents, and 30 adult twin pairs who were all uncertain of their zygosity, to
complete one pen and paper questionnaire and one online questionnaire about their
assumed zygosity, reasons for their assumptions and the importance of accurate
zygosity knowledge. Responses were compared with their true zygosity measured
using a genetic test. We found a substantial proportion of parents and twins had
been misinformed by their own parents or medical professionals, and that
knowledge of their true zygosity status provided peace of mind and positive
emotional responses. For these reasons we propose universal zygosity testing of
same-sex twins as early in life as possible and an increase in education of
medical professionals, twins and families of twins about zygosity issues.
PMID- 25851728
TI - The microbiota and microbiome in aging: potential implications in health and age
related diseases.
AB - Advances in bacterial deoxyribonucleic acid sequencing allow for characterization
of the human commensal bacterial community (microbiota) and its corresponding
genome (microbiome). Surveys of healthy adults reveal that a signature composite
of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity,
vagina). A myriad of clinical changes, including a basal proinflammatory state
(inflamm-aging), that directly interface with the microbiota of older adults and
enhance susceptibility to disease accompany aging. Studies in older adults
demonstrate that the gut microbiota correlates with diet, location of residence
(e.g., community dwelling, long-term care settings), and basal level of
inflammation. Links exist between the microbiota and a variety of clinical
problems plaguing older adults, including physical frailty, Clostridium difficile
colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease.
Manipulation of the microbiota and microbiome of older adults holds promise as an
innovative strategy to influence the development of comorbidities associated with
aging.
PMID- 25851729
TI - A minimal standardization setting for language mapping tests: an Italian example.
AB - During awake surgery, picture-naming tests are administered to identify brain
structures related to language function (language mapping), and to avoid
iatrogenic damage. Before and after surgery, naming tests and other
neuropsychological procedures aim at charting naming abilities, and at detecting
which items the subject can respond to correctly. To achieve this goal,
sufficiently large samples of normed and standardized stimuli must be available
for preoperative and postoperative testing, and to prepare intraoperative tasks,
the latter only including items named flawlessly preoperatively. To discuss
design, norming and presentation of stimuli, and to describe the minimal
standardization setting used to develop two sets of Italian stimuli, one for
object naming and one for verb naming, respectively. The setting includes a
naming study (to obtain picture-name agreement ratings), two on-line
questionnaires (to acquire age-of-acquisition and imageability ratings for all
test items), and the norming of other relevant language variables. The two sets
of stimuli have >80 % picture-name agreement, high levels of internal consistency
and reliability for imageability and age of acquisition ratings. They are normed
for psycholinguistic variables known to affect lexical access and retrieval, and
are validated in a clinical population. This framework can be used to increase
the probability of reliably detecting language impairments before and after
surgery, to prepare intraoperative tests based on sufficient knowledge of pre
surgical language abilities in each patient, and to decrease the probability of
false positives during surgery. Examples of data usage are provided. Normative
data can be found in the supplementary materials.
PMID- 25851730
TI - An inverse association between serum vitamin D levels with the presence and
severity of impaired nerve conduction velocity and large fiber peripheral
neuropathy in diabetic subjects.
AB - Diabetic neuropathy (DN) is the most common complication of diabetes mellitus
(DM) and also the major cause of morbidity and mortality in diabetic patients.
There have been recent speculations that circulating 25-hydroxyvitamin D (25(OH)
D) could be involved in DN development and progression. This study explored the
association between serum 25(OH)-D and DN in diabetic subjects by performing
strict matching of possible confounders. Overall, 33 diabetic subjects with DN
and 29 controls matched in terms of age, sex, BMI, height and disease duration
entered this study. Nerve conduction velocity (NCV) was performed to determine
the existence and severity of large fiber neuropathy. 25(OH)-D had significantly
lower value in DN group (21.2 +/- 11.5 vs. 13.5 +/- 5.1 ng/mL, P = 0.001). None
of the other observed variables showed a significant association with existence
and severity of DN. After adjustment for all studied variables, serum vitamin D
had an independent and inverse association with both DN presence and severity, as
each 1 ng/mL increase in serum 25(OH)-D was correlated with 2.2 and 3.4 %
decrease in the presence and severity of NCV impairment, respectively. While
adjusted for demographic variables, comorbidities and treatment of DM, our
results imply that decreased levels of circulating 25(OH)-D may contribute to
increased risk of large fiber neuropathy in type 2 diabetic subjects.
PMID- 25851731
TI - Usual coffee intake in Brazil: results from the National Dietary Survey 2008-9.
AB - Coffee is central to the economy of many developing countries, as well as to the
world economy. However, despite the widespread consumption of coffee, there are
very few available data showing the usual intake of this beverage. Surveying
usual coffee intake is a way of monitoring one aspect of a population's usual
dietary intake. Thus, the present study aimed to characterise the usual daily
coffee intake in the Brazilian population. We used data from the National Dietary
Survey collected in 2008-9 from a probabilistic sample of 34,003 Brazilians aged
10 years and older. The National Cancer Institute method was applied to obtain
the usual intake based on two nonconsecutive food diaries, and descriptive
statistical analyses were performed by age and sex for Brazil and its regions.
The estimated average usual daily coffee intake of the Brazilian population was
163 (SE 2.8) ml. The comparison by sex showed that males had a 12% greater usual
coffee intake than females. In addition, the highest intake was recorded among
older males. Among the five regions surveyed, the North-East had the highest
usual coffee intake (175 ml). The most common method of brewing coffee was
filtered/instant coffee (71%), and the main method of sweetening beverages was
with sugar (87%). In Brazil, the mean usual coffee intake corresponds to 163 ml,
or 1.5 cups/d. Differences in usual coffee intake according to sex and age
differed among the five Brazilian regions.
PMID- 25851732
TI - Performance status and depressive symptoms as predictors of quality of life in
cancer patients. A structural equation modeling analysis.
AB - OBJECTIVE: This study aimed to examine whether depressive symptoms and
performance status are independent predictors of both the physical and
psychological domains of health-related quality of life (HRQoL) in cancer
patients. METHODS: A sample of 4020 cancer patients (mean age 58 years, 51%
women) was evaluated. Depressive symptoms were measured with the patient health
questionnaire and HRQoL with the European Organisation for Research and Treatment
of Cancer quality of life questionnaire core 30. The impact of the illness on
everyday activities was assessed with physician ratings of both the Karnofsky
performance status and the Eastern Cooperative Oncology Group performance status.
The simultaneous effects of depression and performance status on quality of life
outcomes were estimated using structural equation modeling. RESULTS: Both
depressive symptoms and performance status independently predicted the physical
and psychological domains of HRQoL. However, the impact of depressive symptoms on
the physical HRQoL was stronger than the impact of performance status on the
psychological HRQoL. CONCLUSION: Our results suggest that comorbid depressive
symptoms are independently associated with both physical and psychological HRQoL
in cancer patients after controlling for the physician-rated performance status.
Thus, comorbid depression should be taken into account when evaluating reduced
HRQoL in cancer patients. To support a causal impact of depression on HRQoL,
intervention studies are needed to show that improving depression enhances cancer
patients' HRQoL.
PMID- 25851733
TI - Making big communities small: using network science to understand the ecological
and behavioral requirements for community social capital.
AB - The concept of social capital is becoming increasingly common in community
psychology and elsewhere. However, the multiple conceptual and operational
definitions of social capital challenge its utility as a theoretical tool. The
goals of this paper are to clarify two forms of social capital (bridging and
bonding), explicitly link them to the structural characteristics of small world
networks, and explore the behavioral and ecological prerequisites of its
formation. First, I use the tools of network science and specifically the concept
of small-world networks to clarify what patterns of social relationships are
likely to facilitate social capital formation. Second, I use an agent-based model
to explore how different ecological characteristics (diversity and segregation)
and behavioral tendencies (homophily and proximity) impact communities' potential
for developing social capital. The results suggest diverse communities have the
greatest potential to develop community social capital, and that segregation
moderates the effects that the behavioral tendencies of homophily and proximity
have on community social capital. The discussion highlights how these findings
provide community-based researchers with both a deeper understanding of the
contextual constraints with which they must contend, and a useful tool for
targeting their efforts in communities with the greatest need or greatest
potential.
PMID- 25851734
TI - Effect of hepatic insulin expression on lipid metabolism in diabetic mice.
AB - BACKGROUND: Hypertriglyceridemia is a common lipid disorder that is characterized
by elevated plasma levels of triglyceride (TG)-rich particles, such as very low
density lipoprotein (VLDL), in poorly controlled diabetes. The aim of the present
study was to determine the potential therapeutic effect of hepatic insulin
production on hypertriglyceridemia in mice. METHODS: Mice were induced diabetic
and hypertriglyceridemic by streptozotocin (STZ) treatment. Using an adenovirus
mediated gene transfer approach, we delivered rat preproinsulin cDNA into the
liver of diabetic mice and then determined plasma TG metabolism. To investigate
the mechanism by which hepatic insulin improves TG metabolism, we determined
hepatic expression of apolipoprotein C-III (ApoC-III), a structural moiety and
functional inhibitor of VLDL-TG catabolism. RESULTS: Plasma VLDL-TG levels were
markedly elevated in STZ-treated mice, and were accompanied by hyperglycemia and
hypertriglyceridemia. These metabolic abnormalities were restored to near normal
following hepatic insulin production in insulin vector-treated diabetic mice. In
contrast, hypertriglyceridemia and hyperglycemia persisted in control vector
treated diabetic animals. Hepatic ApoC-III expression became deregulated
secondary to insulin deficiency, contributing to impaired TG metabolism in
diabetic mice. Hepatic insulin production suppressed excessive hepatic ApoC-III
production to basal levels. CONCLUSION: Hepatic insulin production is efficacious
in correcting hypertriglyceridemia associated with insulin deficiency in diabetic
mice.
PMID- 25851735
TI - Parasite host range and the evolution of host resistance.
AB - Parasite host range plays a pivotal role in the evolution and ecology of hosts
and the emergence of infectious disease. Although the factors that promote host
range and the epidemiological consequences of variation in host range are
relatively well characterized, the effect of parasite host range on host
resistance evolution is less well understood. In this study, we tested the impact
of parasite host range on host resistance evolution. To do so, we used the host
bacterium Pseudomonas fluorescens SBW25 and a diverse suite of coevolved viral
parasites (lytic bacteriophage Phi2) with variable host ranges (defined here as
the number of host genotypes that can be infected) as our experimental model
organisms. Our results show that resistance evolution to coevolved phages
occurred at a much lower rate than to ancestral phage (approximately 50% vs.
100%), but the host range of coevolved phages did not influence the likelihood of
resistance evolution. We also show that the host range of both single parasites
and populations of parasites does not affect the breadth of the resulting
resistance range in a naive host but that hosts that evolve resistance to single
parasites are more likely to resist other (genetically) more closely related
parasites as a correlated response. These findings have important implications
for our understanding of resistance evolution in natural populations of bacteria
and viruses and other host-parasite combinations with similar underlying
infection genetics, as well as the development of phage therapy.
PMID- 25851736
TI - Examining the 16-year trajectories of mental health and wellbeing through the
transition into widowhood.
AB - BACKGROUND: Becoming widowed is a significant event. There is considerable
evidence that surviving partners report substantial changes in their wellbeing
and mental health. Changes can occur prior to partner's death as an anticipatory
effect and consequently during the period after partner's death. For most,
declines in wellbeing and mental health dissipate over time. However, there is a
limited long-term evidence to compare age-normative trajectories in mental health
and wellbeing with the trajectories of those who transition into widowhood.
METHODS: Participants (n = 652) were older adults (aged 65-94 years at baseline)
from the 16-year Melbourne Longitudinal Studies on Healthy Ageing project who
were either married or de facto (n = 577), or recently widowed (n = 75).
Generalized Estimating Equations (GEE) examined the immediate and long-term
impact of widowhood. GEE piecewise regression analyses examined the trajectories
of wellbeing and mental health in those who transitioned into widowed with time
centered at time of partner's death. Analyses were stratified by gender. RESULTS:
For both men and women, becoming widowed was strongly related to a strong decline
in positive affect post partner's death. Otherwise, no long-term impact of
widowhood on negative affect or depressive symptomology was reported.
CONCLUSIONS: The impact of widowhood reports differential impacts on different
indicators of wellbeing and mental health, which were inconsistent between men
and women.
PMID- 25851737
TI - An ultrasensitive electrochemical immunosensor for the detection of CD146 based
on TiO2 colloidal sphere laden Au/Pd nanoparticles.
AB - An ultrasensitive electrochemical immunosensor for the detection of cluster of
differentiation 146 antigen (CD146) based on TiO2 colloidal sphere laden Au/Pd
nanoparticles (Au/Pd@TiO2) was developed. In this work, reduced graphene oxide
tetraethylene pentamine (rGO-TEPA) was applied as an electrode modifying material
to modify the surface of a glassy carbon electrode (GCE). Au/Pd@TiO2 was used as
the secondary-antibody (Ab2) label for the fabrication of the immunosensor.
Amperometric response of the immunosensor for electrocatalytic reduction of
hydrogen peroxide (H2O2) was recorded. Electrochemical impedance spectroscopy
(EIS) proved that fabrication of the immunosensor was successful. The anti-CD146
primary antibody (Ab1) was immobilized on the rGO-TEPA modified GCE by a cross
linking reagent of glutaraldehyde (GA). With Ab1 immobilized onto the rGO-TEPA
modified GCE and Ab2 linked with Au/Pd@TiO2, the immunosensor displayed a wide
linear range (0.0050-20 ng mL(-1)), a low detection limit (1.6 pg mL(-1)), good
reproducibility, good selectivity and acceptable stability. The designed sensing
strategy may provide a potential application in the detection of other tumor
markers.
PMID- 25851738
TI - Evaluating clinical implications of 15-mega-sub-pixel liquid-crystal display in
phase-contrast mammography.
AB - BACKGROUND: Phase-contrast mammography (PCM) systems characteristically yield
sharp images with edge enhancement and high-resolution 25-MUm/pixel mammograms.
However, not all PCM image information can be shown on the display at a
resolution of 5-megapixel (5-MP), although 5-MP monitors are recommended for
interpretation of digital mammograms. Therefore, we investigated the potential
utility of a 15-mega-sub-pixel (15-MsP) display for PCM images. METHODS: We used
a monitor that offered both 5-MP and 15-MsP displays by using a sub-pixel drive
(SPD) technique to increase the spatial resolution of the monitor by threefold in
the direction of the sub-pixels. Contrast-detail mammography phantom images were
evaluated visually by four radiologic technologists. In this study, four display
magnification ratios were used and the calculated image quality figures (IQFs)
were compared with those of a 5-MP display. RESULTS: The detection capability of
the 15-MsP display was significantly better than that of the 5-MP display at
magnification ratios of 49 and 100 %. At other magnification ratios, the
detection capability of the 15-MsP display was higher than that of the 5-MP
display, but the difference was not significant. CONCLUSIONS: A 15-MsP display
has the potential to provide better detection than that provided by conventional
5-MP displays. A 15-MsP display using SPD technology is suitable for high
resolution digital mammograms, such as those produced by PCM systems.
PMID- 25851739
TI - Latent tuberculosis infection screening in immigrants to low-incidence countries:
a meta-analysis.
AB - BACKGROUND: Immigration from regions with a high incidence of tuberculosis (TB)
has slowed the decline of TB in low-incidence regions. Targeted screening of new
immigrants and treatment for latent TB infection (LTBI) is needed to reinvigorate
this decline. This meta-analysis compares LTBI diagnostic tests by positive test
prevalence and proportion of positive tests by TB incidence. METHODS: A
systematic literature search was performed and data extracted based on tuberculin
skin test (TST) and/or interferon-gamma release assay (IGRA) use in immigrants.
For the eight studies performing tests concurrently, data were compared by
positive tests and concordance, while other studies comparing individual tests
were analyzed based on demographic factors. Data were analyzed via meta-analysis.
RESULTS: Forty-five studies with a combined sample size of 93,249 individuals
were included in the analyses, 2206 of which were from the eight concurrent
studies. Odds of a positive TST were significantly higher than an IGRA (odds
ratio 1.46; 95% confidence interval 1.07-2.01) and test agreement was moderate.
Proportion of positive TST and IGRA tests increased with TB incidence, although
not linearly. CONCLUSION: TST and IGRA data relating to immigrants are lacking,
especially long-term follow-up and comparative data. Further data are urgently
needed to determine TB risks after immigration, long-term TB development, and
treatment outcomes.
PMID- 25851741
TI - The effect of sirolimus-based immunosuppression vs. conventional prophylaxis
therapy on cytomegalovirus infection after liver transplantation.
AB - OBJECTIVE: The aim of this study was to assess the efficacy of sirolimus-based
immunosuppression vs. conventional prophylaxis therapy in preventing
cytomegalovirus (CMV) infection or disease in liver transplantation recipients.
METHODS: One hundred and twenty-seven consecutive liver transplant recipients,
with a minimum of one-yr follow-up from 2008 to 2013 in the first affiliated
hospital of Nanchang University, were retrospectively divided into the sirolimus
treated (n = 51) and ganciclovir-treated (n = 76) groups. The CMV incidence,
rejection events, and survival rate were compared. RESULTS: The overall
incidences of CMV events were decreased but did not reach statistical
significance in the sirolimus arm compared with the ganciclovir arm (p > 0.05) at
one yr after liver transplantation. There was no significant difference in the
rejection incidence and survival rates between the two groups. CONCLUSIONS:
Sirolimus-based immunosuppression had a lower incidence of CMV infection compared
with conventional prophylaxis therapy and did not increase rejection risks and
mortality after liver transplantation, indicating that with the use of an
mammalian target-of-rapamycin (mTOR)-inhibitor, CMV prophylaxis may be
dispensable.
PMID- 25851742
TI - Ocular motor measures of cognitive dysfunction in multiple sclerosis II: working
memory.
AB - Our companion paper documents pervasive inhibitory deficits in multiple sclerosis
(MS) using ocular motor (OM) measures. Here we investigated the utility of an OM
working memory (WMem) task in characterising WMem deficits in these patients as a
function of disease status and disease duration. 22 patients with CIS, 22 early
clinically definite MS patients (CDMS: <7 years of diagnosis), 22 late CDMS
patients (>7 years from diagnosis), and 22 healthy controls participated. All
participants completed the ocular motor WMem task, the paced auditory serial
addition test (PASAT), and the symbol digit modalities test (SDMT). Clinical
disability was characterised in CDMS patients using the Expanded Disability
Severity Scale (EDSS). WMem performance was measured as proportion of errors
(WMem errors), saccade latency, and relative sensitivity to WMem loading (WMem
effect), an indicator of WMem capacity. All patient groups performed more WMem
errors than controls with proportion of WMem errors, and degree of WMem effect
increasing with increasing disease duration. A larger WMem effect, reflecting
poorer WMem capacity, corresponded to poorer performance on neuropsychological
measures, and a higher disability score for CDMS patients with the longest
disease duration; an observation that suggests wider implication of WMem
executive processes with advancing disease. Conspicuously, performance decrements
on standard neuropsychological testing did not similarly increase commensurate
with disease duration. The ocular motor WMem task appears to meaningfully
dissociate WMem deficit from healthy individuals as well as a function of
increasing disease duration. Potentially, this task represents a highly
informative and objective method by which to ascertain progressive WMem changes
from the earliest inception of MS.
PMID- 25851744
TI - High-risk prostate cancer and radical prostatectomy in the setting and context of
multidisciplinary care.
PMID- 25851743
TI - Ocular motor measures of cognitive dysfunction in multiple sclerosis I:
inhibitory control.
AB - Our ability to control and inhibit behaviours that are inappropriate, unsafe, or
no longer required is crucial for functioning successfully in complex
environments. Here, we investigated whether a series of ocular motor (OM)
inhibition tasks could dissociate deficits in patients with multiple sclerosis
(MS), including patients with only a probable diagnosis (clinically isolated
syndrome: CIS), from healthy individuals as well as a function of increasing
disease duration. 25 patients with CIS, 25 early clinically definite MS patients
(CDMS: <=7 years of diagnosis), 24 late CDMS patients (>7 years from diagnosis),
and 25 healthy controls participated. All participants completed a series of
classic OM inhibition tasks [antisaccade (AS) task, memory-guided (MG) task,
endogenous cue task], and a neuropsychological inhibition task [paced auditory
serial addition test (PASAT)]. Clinical disability was characterised in CDMS
patients using the Expanded Disability Severity Scale (EDSS). OM (latency and
error) and PASAT performance were compared between patient groups and controls,
as well as a function of disease duration. For CDMS patients only, results were
correlated with EDSS score. All patient groups made more errors than controls on
all OM tasks; error rate did not increase with increasing disease duration. In
contrast, saccade latency (MG and endogenous cue tasks) was found to worsen with
increasing disease duration. PASAT performance did not discriminate patient
groups or disease duration. The EDSS did not correlate with any measure. These OM
measures appear to dissociate deficit between patients at different disease
durations. This suggests their utility as a measure of progression from the
earliest inception of the disease.
PMID- 25851745
TI - Prevalence of gastrointestinal parasites in captive non-human primates of twenty
four zoological gardens in China.
AB - Captive primates are susceptible to gastrointestinal (GIT) parasitic infections,
which are often zoonotic and can contribute to morbidity and mortality. Fecal
samples were examined by the means of direct smear, fecal flotation, fecal
sedimentation, and fecal cultures. Of 26.51% (317/1196) of the captive primates
were diagnosed gastrointestinal parasitic infections. Trichuris spp. were the
most predominant in the primates, while Entamoeba spp. were the most prevalent in
Old World monkeys (P < 0.05). These preliminary data will improve the management
of captive primates and the safety of animal keepers and visitors.
PMID- 25851746
TI - Copper oxide and zinc oxide nanomaterials act as inhibitors of multidrug
resistance transport in sea urchin embryos: their role as chemosensitizers.
AB - The ability of engineered nanomaterials (NMs) to act as inhibitors of ATP-binding
cassette (ABC) efflux transporters in embryos of white sea urchin (Lytechinus
pictus) was studied. Nanocopper oxide (nano-CuO), nanozinc oxide (nano-ZnO), and
their corresponding metal ions (CuSO4 and ZnSO4) were used as target chemicals.
The results showed that nano-CuO, nano-ZnO, CuSO4, and ZnSO4, even at relatively
low concentrations (0.5 ppm), significantly increased calcein-AM (CAM, an
indicator of ABC transporter activity) accumulation in sea urchin embryos at
different stages of development. Exposure to nano-CuO, a very low solubility NM,
at increasing times after fertilization (>30 min) decreased CAM accumulation, but
nano-ZnO (much more soluble NM) did not, indicating that metal ions could cross
the hardened fertilization envelope, but not undissolved metal oxide NMs.
Moreover, nontoxic levels (0.5 ppm) of nano-CuO and nano-ZnO significantly
increased developmental toxicity of vinblastine (an established ABC transporter
substrate) and functioned as chemosensitizers. The multidrug resistance
associated protein (MRP, one of ABC transporters) inhibitor MK571 significantly
increased copper concentrations in embryos, indicating ABC transporters are
important in maintaining low intracellular copper levels. We show that low
concentrations of nano-CuO and nano-ZnO can make embryos more susceptible to
other contaminants, representing a potent amplification of nanomaterial-related
developmental toxicity.
PMID- 25851747
TI - Towards the resolution of a long-standing evolutionary question: muscle identity
and attachments are mainly related to topological position and not to primordium
or homeotic identity of digits.
AB - Signaling for limb bone development usually precedes that for muscle development,
such that cartilage is generally present before muscle formation. It remains
obscure, however, if: (i) tetrapods share a general, predictable spatial
correlation between bones and muscles; and, if that is the case, if (ii) such a
correlation would reflect an obligatory association between the signaling
involved in skeletal and muscle morphogenesis. We address these issues here by
using the results of a multidisciplinary analysis of the appendicular muscles of
all major tetrapod groups integrating dissections, muscle antibody stainings,
regenerative and ontogenetic analyses of fluorescently-labeled (GFP) animals, and
studies of non-pentadactyl human limbs related to birth defects. Our synthesis
suggests that there is a consistent, surprising anatomical pattern in both normal
and abnormal phenotypes, in which the identity and attachments of distal limb
muscles are mainly related to the topological position, and not to the
developmental primordium (anlage) or even the homeotic identity, of the digits to
which they are attached. This synthesis is therefore a starting point towards the
resolution of a centuries-old question raised by authors such as Owen about the
specific associations between limb bones and muscles. This question has crucial
implications for evolutionary and developmental biology, and for human medicine
because non-pentadactyly is the most common birth defect in human limbs. In
particular, this synthesis paves the way for future developmental experimental
and mechanistic studies, which are needed to clarify the processes that may be
involved in the elaboration of the anatomical patterns described here, and to
specifically test the hypothesis that distal limb muscle identity/attachment is
mainly related to digit topology.
PMID- 25851748
TI - Deviant early pregnancy maternal triglyceride levels and increased risk of
congenital anomalies: a prospective community-based cohort study.
AB - OBJECTIVE: The maternal lipid profile could be of importance in congenital
anomaly development. This study therefore investigates whether the maternal lipid
profile during early pregnancy is associated with major nonsyndromic congenital
anomalies (MNCA). DESIGN: Prospective community-based cohort study. SETTING:
Amsterdam Born Children and their Development (ABCD) study. POPULATION: A cohort
of 3074 pregnant women recruited in 2003-2004 and their offspring. METHODS: Non
fasting blood samples from pregnant women participating in the ABCD-study (median
12.9 weeks of gestation) were analysed for triglycerides (TG), cholesterol (TC),
free fatty acids (FFA), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA) (n
= 3074). The perinatal outcome (MNCA) was obtained from the Youth Health Care
Registration and two questionnaires. Adjustment was made for ethnicity. MAIN
OUTCOME MEASURE: MNCA prevalence. RESULTS: The prevalence of MNCA was 2.2% (n =
68: 20 cardiovascular, 25 bone and muscle, and 23 other single anomalies). A
nonlinear association was found between maternal TG levels and MNCA prevalence.
With a lower or higher level of maternal TG, the estimated probability increased:
a TG level of 0.73 mmol/l (5th percentile), of 1.28 mmol/l (50th percentile), and
of 2.35 mmol/l (95th percentile) corresponded with an estimated probability of
3.6, 2.1, and 2.9%, respectively. Unadjusted subgroup analyses showed that the U
shaped association was most prominent for cardiovascular congenital anomalies.
Other lipids were not associated with MNCA. CONCLUSIONS: Both low and high
maternal TG levels during early pregnancy were associated with an increased risk
of MNCA in offspring. This suggests that an attempt should be made to normalise
TG levels before or during early pregnancy; however, replication of our results
is necessary before clinical practice recommendations can be made.
PMID- 25851749
TI - A highly sensitive square wave voltammetry based biosensor for kinase activity
measurements.
AB - An electrochemical biosensor has been developed for ultrasensitive, label-free
determination of protein kinase activity. The sensor is composed of a unique
peptide monolayer on a gold electrode. It identifies the order change in the
monolayer upon phosphorylation, via square wave voltametry (SWV) measurements.
Disorder caused by the introduction of the phosphate groups onto the middle of
the peptide sequence results in pinhole formation and therefore an increase in
the electrochemical signal. The measured sensitivity was 100 nM of kinase and the
dynamic range was 100 nM up to 11 MUM. Sensitivity was an order of magnitude
higher, and the dynamic range wider by two orders of magnitude, as compared to
our previously reported impedimetric method, in which the sensitivity was 1 MUM,
and the dynamic range was 1-20 MUM.
PMID- 25851750
TI - Serum antibody levels correlate with oral fungal cell numbers and influence the
patients' response to chronic paracoccidioidomycosis.
AB - Paracoccidioidomycosis (PCM) is a neglected fungal disease that elicits an
important granulomatous inflammatory reaction which aims to isolate the fungi and
resolve the infection; besides the innate cellular response, the patients' sera
may contain different levels of antibodies directed against PCM's pathogenic
agent: Paracoccidioides brasiliensis (Pb). The aim of the study was to assess the
distinct serum antibody levels of 19 chronic PCM patients and to associate these
levels to the granulomatous inflammatory response and presence of fungi in oral
lesions caused by Pb. The presence of Pb was detected and counted within oral
tissues using immunohistochemistry; antibody levels were classified as negative,
low-grade, moderate or high-grade groups. The Kruskal-Wallis and Dunn's test were
used to verify possible associations among the groups. Interestingly, lower
antibody titres were associated with lesser numbers of Pb, which favours the
cellular response over the humoral response to fight PCM. On the other hand,
negative serological results were linked to a higher presence of Pb in the
tissues, indicating that a deficient humoral response supports the fungal
proliferation. The number of Pb was conveniently associated with the level of
serum antibodies, showing that the humoral immune response is required, however,
not solely responsible to restrain the dissemination of Pb.
PMID- 25851751
TI - Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a
systematic review and meta-analysis.
AB - Vortioxetine has a beneficial pharmacological profile for reducing anxiety and
depression. Recently, a number of randomized, double-blind, placebo-controlled
clinical trials (RCTs) of vortioxetine have been conducted in patients with
generalized anxiety disorder (GAD); however, the results from GAD RCTs are
inconsistent. With an extensive search of databases and clinical trial
registries, four published short-term RCTs were identified and included in the
present meta-analysis. The mean change in total scores on the Hamilton Anxiety
Rating Scale (HAMA) from baseline was the primary endpoint. The secondary
endpoints included the response and remission rates, as defined by a >=50%
reduction in HAMA total scores and a <=7 change in the HAMA total score at the
end of treatment. In addition, the mean change in the HAMA total score from
baseline in the subgroup with a HAMA total score >=25 at baseline was included.
Vortioxetine was significantly more effective than was placebo, with a
standardized mean difference (SMD) of -0.118 (95% CIs, -0.203 to -0.033, P =
0.007). In particular, those with severe GAD (HAMA total score >=25 at baseline)
had a significantly greater benefit from vortioxetine than those without (SMD =
0.338, 95% CIs = -0.552 to -0.124, p = 0.002). The odds ratios (ORs) for
vortioxetine for response and remission were 1.221 (95% CIs, 1.027 to 1.452, P =
0.024) and 1.052 (95% CIs, 0.853 to 1.296, P = 0.637), respectively.
Discontinuation due to adverse events (AEs) (OR = 1.560, 1.006 to 2.419, p =
0.047) was marginally higher in vortioxetine than placebo treatment, whereas
discontinuation due to any reason (OR = 0.971, 0.794 to 1.187, p = 0.771) and
inefficacy (OR = 0.687, 0.380 to 1.243, p = 0.215) were not significantly
different among treatment groups. Although our results suggest that vortioxetine
may have a potential as an another treatment option for GAD (especially for
severe GAD), they should be interpreted and translated into clinical practice
with caution, as the meta-analysis was based on a limited number of RCTs.
PMID- 25851752
TI - Interstitial granulomatous dermatitis due to borreliosis.
PMID- 25851753
TI - Acquired linear Becker's nevus on lower limb in blaschkoid pattern.
PMID- 25851755
TI - Clinical and dermoscopic features of eccrine poroma.
PMID- 25851754
TI - Novel transglutaminase 1 mutations in a Chinese patient with severe lamellar
ichthyosis phenotype.
PMID- 25851756
TI - Weekly azathioprine pulse versus daily azathioprine in the treatment of
Parthenium dermatitis: A non-inferiority randomized controlled study.
AB - BACKGROUND: Azathioprine in daily doses has been shown to be effective and safe
in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP)
are also effective, but there are no reports comparing the effectiveness and
safety of these two regimens in this condition. AIMS: To study the efficacy and
safety of WAP and daily azathioprine in Parthenium dermatitis. METHODS: Sixty
patients with Parthenium dermatitis were randomly assigned to treatment with
azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months.
Patients were evaluated every month to assess the response to treatment and side
effects. RESULTS: The study included 32 patients in the weekly azathioprine group
and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively
completed the study. Twenty-three (92%) patients on WAP and 21 (96%) on daily
azathioprine had a good or excellent response. The mean pretreatment clinical
severity score decreased from 26.4+/-14.5 to 4.7+/-5.1 in the WAP group, and from
36.1+/-18.1 to 5.7+/-6.0 in the daily azathioprine group, which was statistically
significant and comparable (P=0.366). Patients on WAP had a higher incidence of
adverse effects (P=0.02). LIMITATIONS: The study had a small sample size and the
amount of clobetasol propionate used in each patient was not determined, though
it may not have affected the study outcome due to its comparable use in both
groups. CONCLUSIONS: Azathioprine 300 mg weekly pulse and 100 mg daily dose are
equally effective and safe in the treatment of Parthenium dermatitis.
PMID- 25851757
TI - Histopathological evidence of efficacy of microneedle radiofrequency for
treatment of axillary hyperhidrosis.
PMID- 25851758
TI - Progressive cribriform and zosteriform hyperpigmentation.
PMID- 25851759
TI - Bullous eosinophilic cellulitis with subcorneal pustules.
PMID- 25851760
TI - Leser-Trelat sign with primary hepatic carcinoma.
PMID- 25851761
TI - Evaluation of the effect of Block Level Awareness Campaign on performance
indicators of National Leprosy Elimination Program in Vadodara district, Gujarat,
India.
AB - BACKGROUND: Leprosy is probably the oldest disease afflicting mankind and a
public health problem for centuries. Many cases are hidden or undiagnosed,
especially due to social stigma, and neglect of painless patches. Between years
2001 and 2005, during which time active surveillance for detection of leprosy was
in practice, a steep fall in the prevalence rate (PR) of leprosy was observed.
However, during later years, leprosy program discontinued active surveillance for
detection of leprosy cases. Presently block level awareness campaign (BLAC) is a
special measure undertaken in a campaign mode during September-November in
priority areas, (PR>1/10000 population), during which information, education and
communication (IEC) activities and active surveillance of leprosy cases is done.
AIMS: To evaluate the effect of Block Level Awareness Campaign on performance
indicators of national leprosy elimination program (NLEP) in Vadodara district.
METHODS: The campaign was carried out for 6 days in 12 talukas of Vadodara
district by the district leprosy office, Vadodara. Trained teams of health
workers carried out information, education and communication (IEC) activity and
active surveillance by undertaking house to house survey in each primary health
centre (PHC) area. Suspected cases were identified by the team and confirmed
clinically by medical officers in the primary health centre of the corresponding
areas. A district nucleus team (DNT) validated these confirmed cases. These data
were compared with the district's national leprosy eradication programme (NLEP)
data for the same year, 2012 and the previous year, 2011. RESULTS: A total of
1,574,586 persons, comprising 76%of the population surveyed, were screened for
leprosy, which resulted in detection of 358 clinically confirmed new cases of
leprosy, out of which 225 (62.8%) were paucibacillary (PB) and 133 (37.2%) were
multibacillary (MB) leprosy. Of these cases, 14 (4%) had deformities, and 37
(10.3%) were children. LIMITATIONS: Only 76% of the population could be covered.
Histopathological confirmation of the diagnosis was not undertaken. Because of
the large number of health workers invovled, variations in their skills may have
influenced the diagnosis of suspected cases. CONCLUSIONS: Active surveillance
linked to focused block level campaigns can be useful tools to detect new hidden
leprosy cases.
PMID- 25851762
TI - Pemphigus vulgaris localised exclusively to the penis.
PMID- 25851763
TI - Clinical and histological patterns of dermatofibroma without gross skin surface
change: A comparative study with conventional dermatofibroma.
AB - BACKGROUND: Dermatofibroma sometimes clinically presents as a nodular lesion
without gross skin surface change. Clinicopathologic features of this variant of
dermatofibroma have not been evaluated. AIMS: To assess clinicopathologic
features of dermatofibroma presenting as a subcutaneous nodule. METHODS: This
study reviewed the clinical and histological features of 42 cases of subcutaneous
dermatofibromas and compared them with 95 cases of conventional dermatofibroma.
RESULTS: Dermatofibroma without gross skin surface change was associated with a
shorter pre-diagnosis duration than conventional dermatofibroma. Increase in size
during the pre-diagnosis period was significantly more frequent in the
conventional type. In addition, these dermatofibromas were more likely than the
conventional type to occur in the head and neck region. Although tumor depth was
deeper than in the conventional type, less than half of the dermatofibromas
without gross skin surface change were found histologically to be "subcutaneous"
or "deep-penetrating dermatofibroma". Subcutaneous extension was more frequent in
these dermatofibromas while focal stromal hyalinization and hemosiderin deposits
were more common in the conventional type. LIMITATIONS: This study is a
retrospective, single center design. CONCLUSION: The present study suggests that
dermatofibroma without gross skin surface change is a variant type with distinct
clinical and histological features that distinguish them from conventional
dermatofibroma.
PMID- 25851764
TI - Onychomycosis: A study of self-recognition by patients and quality of life.
AB - BACKGROUND: Onychomycosis accounts for approximately half of all nail disorders
and is usually asymptomatic. OBJECTIVES: To evaluate patients' recognition of
fungal nail disease, concomitant fungal skin diseases, complications, and quality
of life. METHODS: Patients from the fungal nail clinic were enrolled between May
2011 and April 2012. Patients' awareness of diseased nails was evaluated and the
Dermatology Life Quality Index (DLQI) questionnaire was used to evaluate the
impact of dermatologic disease on quality of life. RESULTS: A total of 110
patients with onychomycosis were enrolled in the study, of which 64 (58.2%) were
female and the mean age was 60.8 years. The number of patients who were able to
recognize the presence of onychomycosis was 71 (64.5%), while 32 (29.1%) and 7
(6.4%) were diagnosed by a dermatologist and other physicians, respectively.
Multivariate analysis showed that patient recognition of the disease was
significantly associated with female sex and young age. The mean DLQI score was
3.6. LIMITATION: Patient recall bias including the duration of fungal nail
infection, long-term past history and previous treatment was a limitation of this
study that affected DLQI scores. CONCLUSION: About half of onychomycosis
patients, especially elderly males, could not recognize the disease by
themselves. It is important for physicians to educate patients with risk factors
for onychomycosis to recognize this condition early to prevent concomitant
infection and complications, and to improve patients' well-being.
PMID- 25851765
TI - Chalazion clamp in dermatology revisited.
PMID- 25851766
TI - Type of anesthesia and differences in clinical outcome after intra-arterial
treatment for ischemic stroke.
AB - BACKGROUND AND PURPOSE: Intra-arterial treatment (IAT) in patients with acute
ischemic stroke (AIS) can be performed with or without general anesthesia (GA).
Previous studies suggested that IAT without the use of GA (non-GA) is associated
with better clinical outcome. Nevertheless, no consensus exists about the
anesthetic management during IAT of AIS patients. This study investigates the
association between type of anesthesia and clinical outcome in a large cohort of
patients with AIS treated with IAT. METHODS: All consecutive patients with AIS of
the anterior circulation who received IAT between 2002 and 2013 in 16 Dutch
hospitals were included in the study. Primary outcome was functional outcome on
the modified Rankin Scale at discharge. Difference in primary outcome between GA
and non-GA was estimated using multiple ordinal regression analysis, adjusting
for age, stroke severity, occlusion of the internal carotid artery terminus,
previous stroke, atrial fibrillation, and diabetes mellitus. RESULTS: Three
hundred forty-eight patients were included in the analysis; 70 patients received
GA and 278 patients did not receive GA. Non-GA was significantly associated with
good clinical outcome (odds ratio 2.1, 95% confidence interval 1.02-4.31). After
adjusting for prespecified prognostic factors, the point estimate remained
similar; statistical significance, however, was lost (odds ratio 1.9, 95%
confidence interval 0.89-4.24). CONCLUSIONS: Our study suggests that patients
with AIS of the anterior circulation undergoing IAT without GA have a higher
probability of good clinical outcome compared with patients treated with general
anesthesia.
PMID- 25851768
TI - Endovascular treatment for ischemic strokes with large vessel occlusion: proven
therapy and bright future.
PMID- 25851767
TI - Hospital costs associated with atrial fibrillation for patients with ischemic
stroke aged 18-64 years in the United States.
AB - BACKGROUND AND PURPOSE: Hospital costs associated with atrial fibrillation (AFib)
among patients with stroke have not been well-studied, especially among people
aged <65 years. We estimated the AFib-associated hospital costs in US patients
aged 18 to 64 years. METHODS: We identified hospital admissions with a primary
diagnosis of ischemic stroke from the 2010 to 2012 MarketScan Commercial Claims
and Encounters inpatient data sets, excluding those with capitated health
insurance plans, aged <18 or >64 years, missing geographic region, hospital costs
below the 1st or above 99th percentile, and having carotid intervention (n=40
082). We searched the data for AFib and analyzed the costs for nonrepeat and
repeat stroke admissions separately. We estimated the AFib-associated costs using
multivariate regression models controlling for age, sex, geographic region, and
Charlson comorbidity index. RESULTS: Of the 33 500 nonrepeat stroke admissions,
2407 (7.2%) had AFib. Admissions with AFib cost $4991 more than those without
AFib ($23 770 versus $18 779). For the 6582 repeat stroke admissions, 397 (6.0%)
had AFib. The costs were $3260 more for those with AFib than those without ($24
119 versus $20 929). After controlling for potential confounders, AFib-associated
costs for nonrepeat stroke admissions were $4905, representing 20.6% of the total
costs for the admissions. Both the hospital costs and the AFib-associated costs
were associated with age, but not with sex. AFib-associated costs for repeat
stroke admissions were not significantly higher than for non-AFib patients,
except for those aged 55 to 64 years ($3537). CONCLUSIONS: AFib increased the
hospital cost of ischemic stroke substantially. Further investigation on AFib
associated costs for repeat stroke admissions is needed.
PMID- 25851769
TI - Prognostications of fibrillations.
PMID- 25851770
TI - Delayed Administration of Tat-HA-NR2B9c Promotes Recovery After Stroke in Rats.
AB - BACKGROUND AND PURPOSE: Previous studies reported that Tat-NR2B9c, a peptide
disrupting the N-methyl-d-aspartate receptor-postsynaptic density protein-95
interaction, reduced ischemic damage in the acute phase after stroke. However,
its effect in the subacute phase is unknown. The aim of this study is to
determine whether disrupting the N-methyl-d-aspartate receptor-postsynaptic
density protein-95 interaction in the subacute phase promotes recovery after
stroke. METHODS: Studies were performed on Sprague-Dawley rats or nNOS(-/-) mice,
and experimental ischemic stroke was induced by middle cerebral artery occlusion.
Animals were treated with drugs starting at day 4 after ischemia. Sensorimotor
functions and spatial learning and memory ability were assessed after drug
treatment. Then, rats were euthanized for morphological observation and
biochemical tests. RESULTS: Disrupting the N-methyl-d-aspartate receptor
postsynaptic density protein-95 interaction with Tat-HA-NR2B9c significantly
ameliorated the ischemia-induced impairments of spatial memory and sensorimotor
functions in rats during subacute stage but did not improve stroke outcome in
nNOS(-/-) mice. Consistent with the functional recovery, Tat-HA-NR2B9c
substantially increased neurogenesis in the dentate gyrus and dendritic spine
density of mature neurons in the motor cortex of rats, meanwhile, reversed the
ischemia-induced formation of S-nitrosylation-cyclin-dependent kinase 5 and
increased cyclin-dependent kinase 5 activity in ipsilateral hippocampus. However,
directly blocking N-methyl-d-aspartate receptors with MK-801 or Ro 25-6981 did
not show the beneficial effects above. CONCLUSIONS: Dissociating N-methyl-d
aspartate receptor-postsynaptic density protein-95 coupling by Tat-HA-NR2B9c in
the subacute phase after stroke promotes functional recovery, probably because of
that it increases neurogenesis and dendritic spine density of mature neurons via
regulating cyclin-dependent kinase 5 in the ischemic brain.
PMID- 25851771
TI - Predictors of finding occult atrial fibrillation after cryptogenic stroke.
AB - BACKGROUND AND PURPOSE: Occult paroxysmal atrial fibrillation (AF) is found in a
substantial minority of patients with cryptogenic stroke. Identifying reliable
predictors of paroxysmal AF after cryptogenic stroke would allow clinicians to
more effectively use outpatient cardiac monitoring and ultimately reduce
secondary stroke burden. METHODS: We analyzed a retrospective cohort of
consecutive patients who underwent 28-day mobile cardiac outpatient telemetry
after cryptogenic stroke or transient ischemic stroke. Univariate and
multivariable analyses were performed to identify clinical, echocardiographic,
and radiographic features associated with the detection of paroxysmal AF.
RESULTS: Of 227 patients with cryptogenic stroke (179) or transient ischemic
stroke (48), 14% (95% confidence interval, 9%-18%) had AF detected on mobile
cardiac outpatient telemetry, 58% of which was >=30 seconds in duration. Age >60
years (odds ratio, 3.7; 95% confidence interval, 1.3-11) and prior cortical or
cerebellar infarction seen on neuroimaging (odds ratio, 3.0; 95% confidence
interval, 1.2-7.6) were independent predictors of AF. AF was detected in 33% of
patients with both factors, but only 4% of patients with neither. No other
clinical features (including demographics, CHA2DS2-VASc [combined stroke risk
score: congestive heart failure, hypertension, age, diabetes, prior
stroke/transient ischemic attack, vascular disease, sex] score, or stroke
symptoms), echocardiographic findings (including left atrial size or ejection
fraction), or radiographic characteristics of the acute infarction (including
location, topology, or number) were associated with AF detection. CONCLUSIONS:
Mobile cardiac outpatient telemetry detects AF in a substantial proportion of
cryptogenic stroke patients. Age >60 years and radiographic evidence of prior
cortical or cerebellar infarction are robust indicators of occult AF. Patients
with neither had a low prevalence of AF.
PMID- 25851772
TI - Time trends in incidence and case fatality of ischemic stroke: the tromso study
1977-2010.
AB - BACKGROUND AND PURPOSE: Ischemic stroke incidence has declined in industrialized
countries the last decades, with possible exception for the youngest age groups.
We estimated age- and sex-specific trends in incidence and case fatality of first
ever ischemic stroke between 1977 and 2010 in a Norwegian municipality. METHODS:
Age-adjusted time trends in incidence from 1977 to 2010 were estimated by
fractional polynomial and Poisson regression, and case fatality by logistic
regression in 36 575 participants of the population-based Tromso Study. RESULTS:
There were 1214 first-ever ischemic strokes within a total follow-up time of 611
176 person-years. The overall age- and sex-adjusted incidence decreased by 24% in
1995 to 2010. In women aged 30 to 49 years, the incidence increased significantly
from 1980 to 2010. In men aged 30 to 49 years, there was a nonsignificant, rising
trend from 1977 to 2010. Men aged 50 to 64 years had similar incidence in 2010
compared with 1989. From the mid-1990s to 2010, the incidence declined
significantly in women aged 50 to 74 years and in men aged 65 to 74 years, but
remained stable in those aged >=75 years. Case fatality decreased significantly
in men aged 30 to 84 years from 1995 to 2010, whereas there was no significant
change in women. CONCLUSIONS: Age-adjusted incidence of first-ever ischemic
stroke increased in young women, declined in women aged 50 to 74 years and men
aged 65 to 74 years and remained stable among the oldest. Case fatality declined
in men aged 30 to 84 years, but not in women.
PMID- 25851773
TI - Left phrenic nerve anatomy relative to the coronary venous system: Implications
for phrenic nerve stimulation during cardiac resynchronization therapy.
AB - The objective of this study was to quantitatively characterize anatomy of the
human phrenic nerve in relation to the coronary venous system, to reduce
undesired phrenic nerve stimulation during left-sided lead implantations. We
obtained CT scans while injecting contrast into coronary veins of 15 perfusion
fixed human heart-lung blocs. A radiopaque wire was glued to the phrenic nerve
under CT, then we created three-dimensional models of anatomy and measured
anatomical parameters. The left phrenic nerve typically coursed over the basal
region of the anterior interventricular vein, mid region of left marginal veins,
and apical region of inferior and middle cardiac veins. There was large variation
associated with the average angle between nerve and veins. Average angle across
all coronary sinus tributaries was fairly consistent (101.3 degrees -111.1
degrees ). The phrenic nerve coursed closest to the middle cardiac vein and left
marginal veins. The phrenic nerve overlapped a left marginal vein in >50% of
specimens.
PMID- 25851774
TI - Red meat intolerance in patients submitted to gastric bypass: a 4-year follow-up
study.
AB - BACKGROUND: Bariatric surgery provides significant weight reduction; however, it
may result in food intolerance followed by gastrointestinal complications that
may lead to nutritional deficiencies. This study evaluated the influence of red
meat intolerance on the dietary pattern, biochemical indicators, and clinical
symptoms after Roux-en-Y gastric bypass (RYGB). METHODS: This retrospective study
evaluated patients 4 years after RYGB. The patients were divided into 2 groups:
patients with and without red meat intolerance, and data for the following were
collected: food intake, anthropometric data, biochemical data, and presence of
nausea, vomiting, weakness, weak nails, and hair loss. The difference between
groups in the times postoperative was determined by ANOVA. RESULTS: Of the 72
patients included in the study, 63 were evaluated during the first postoperative
year, 45 during the second, 56 during the third, and 41 during the fourth. Red
meat intolerance was observed in 49.2%, 42.2%, 46.4%, and 39% of the patients
after 1, 2, 3, and 4 years, respectively. After 1 year, the intolerant group
showed lower calorie, carbohydrate, and iron intake. After 3 years, tolerant
patients showed weight regain (2.9 +/- 5.3 kg), while the intolerant ones
remained stable. There was no difference in the presence of clinical symptoms or
biochemical indicators between groups. CONCLUSION: Red meat intolerance is
frequent after bariatric surgery and may alter energy, iron intake, and weight
loss; however, it is not associated with the presence of clinical symptoms and
biochemical profile.
PMID- 25851775
TI - Comparison of the incidence of cholelithiasis after sleeve gastrectomy and Roux
en-Y gastric bypass in obese patients: a prospective study.
AB - BACKGROUND: Although the risk of cholelithiasis (CL) increases in patients after
Roux-en-Y gastric bypass (RYGB), no prospective study has yet assessed the
incidence of CL after sleeve gastrectomy (SG). OBJECTIVES: To compare,
prospectively, the incidence and predictive factors for CL after both procedures.
METHODS: A postoperative abdominal ultrasound follow-up was proposed to all
patients with an intact gallbladder and who underwent RYGB or SG in Hopital Louis
Mourier from 2008 onward. RESULTS: At least one ultrasound was performed on one
hundred and sixty patients between 6 and 12 months postsurgery, 43 after SG and
117 after RYGB. Age, gender, initial body-mass index, co-morbidities were similar
in both groups. Weight loss (WL) at 6 months was significantly lower after SG
than after RYGB (26.9 +/- 9.2 and 31.3 +/- 7.5 kg, respectively = .001). The
incidences of CL after SG and RYGB were similar (28% versus 34% respectively, P =
.57). Most cases of CL occurred in the first year post surgery. During the follow
up, 12% and 13% of patients who underwent SG and RYGB, respectively, became
symptomatic. WL of>30 kg at 6 months was a risk factor for CL after bariatric
surgery, but we did not find any preoperative predictive factor for gallstone
formation. CONCLUSIONS: Despite lower WL after SG, the incidence of CL after SG
and RYGB was similar at 2 years. Our results suggest that rapid WL is the main
element leading to gallstone formation after both procedures.
PMID- 25851776
TI - Does perioperative nutrition and oral carbohydrate load sustainably preserve
muscle mass after bariatric surgery? A randomized control trial.
AB - BACKGROUND: Perioperative nutrition and preoperative oral carbohydrate loading
(CHL) have a beneficial impact on the outcomes of gastrointestinal oncological
surgery. However no data exists on their effect on morbidly obese patients.
OBJECTIVES: Our aim was to establish the short-term and long-term impact of these
modalities, notably on metabolically active lean body mass (LBM) - an important
factor in maintaining long-term weight loss. METHODS: Patients undergoing
laparoscopic Roux-en-Y gastric bypass were randomized to standard management or
intervention: CHL drinks consumed 12 and 2 hours presurgery, and immediate
postoperative peripheral parenteral nutrition. The primary outcome measured was
LBM, measured by Bioelectrical Impedance Analysis (BIA), one and 12 months
postsurgery. Secondary outcomes included excess weight loss (EBWL), 30-day
complication rate, and length of stay. RESULTS: Of the 203 randomized patients,
198 were included in the analysis. All 101 patients in the control group
completed the one-year follow up and 76 completed the BIA. In the intervention
group, 93 of 97 patients completed the one-year follow-up and 71 completed the
BIA. At one and 12 months follow-up, body composition, LBM, or EBWL were
comparable. There was no difference in operative outcomes, complications rates,
or length of stay. There was no adverse effect in the intervention group.
CONCLUSIONS: In a highly homogeneous group of morbidly obese patients with one
year follow-up, CHL and short-term parenteral nutrition did not lead to
significant or sustained LBM preservation or modification in EBWL. There was no
significant decrease in complications or length of stay. Our study confirms the
safety of these interventions, even in previously unstudied Type 2 diabetic
patients.
PMID- 25851778
TI - Effects of cytomegalovirus infection in human neural precursor cells depend on
their differentiation state.
AB - Cytomegalovirus (CMV) is the most common cause of congenital infection in
developed countries and a major cause of neurological disability in children.
Although CMV can affect multiple organs, the most important sequelae of
intrauterine infection are related to lesions of the central nervous system.
However, little is known about the pathogenesis and the cellular events
responsible for neuronal damage in infants with congenital infection. Some
studies have demonstrated that neural precursor cells (NPCs) show the greatest
susceptibility to CMV infection in the developing brain. We sought to establish
an in vitro model of CMV infection of the developing brain in order to analyze
the cellular events associated with invasion by this virus. To this end, we
employed two cell lines as a permanent source of NPC, avoiding the continuous use
of human fetal tissue, the human SK-N-MC neuroblastoma cell line, and an
immortalized cell line of human fetal neural origin, hNS-1. We also investigated
the effect of the differentiation stage in relation to the susceptibility of
these cell lines by comparing the neuroblastoma cell line with the multipotent
cell line hNS-1. We found that the effects of the virus were more severe in the
neuroblastoma cell line. Additionally, we induced hNS-1 to differentiate and
evaluated the effect of CMV in these differentiated cells. Like SK-N-MC cells,
hNS-1-differentiated cells were also susceptible to infection. Viability of
differentiated hNS-1 cells decreased after CMV infection in contrast to
undifferentiated cells. In addition, differentiated hNS-1 cells showed an
extensive cytopathic effect whereas the effect was scarce in undifferentiated
cells. We describe some of the effects of CMV in neural stem cells, and our
observations suggest that the degree of differentiation is important in the
acquisition of susceptibility.
PMID- 25851777
TI - Hypoalbuminemia is disproportionately associated with adverse outcomes in obese
elective surgical patients.
AB - BACKGROUND: Protein deficiency (PD) is a known risk factor for surgical
complications; however, the risks of PD by weight class have not been well
described. It was hypothesized that the combination of obesity and PD is
associated with increased surgical complications compared with normal weight and
normoalbuminemic patients. METHODS: A total of 85,833 general surgery patients
undergoing elective operations within the 2011 National Surgical Quality
Improvement Program were analyzed. Patients with conditions that could
potentially confound serum albumin (SA) were excluded. Patients were stratified
by normal (>3.0 g/dL) versus low (<3.0 g/dL) SA. The relative impact of SA and
body mass index (BMI) (as individual and as combined variables) on surgical
morbidity and mortality were assessed. Multivariate analyses were performed to
identify independent risk factors for morbidity and mortality. RESULTS: Overall,
2,088 (2.43%) patients had low preoperative SA. 587 (28.1%) patients with low
preoperative SA were obese (BMI>30), versus 39,299 (46.9%) with normal
preoperative SA. Importantly, the interaction of hypoalbuminemia and BMI was
independently associated with all complications among hypoalbuminemic patients
with BMI>40, and mortality for patients with BMI>30 after controlling for
appropriate demographic characteristics, co-morbidities, surgical wound
classification, operation type, and complexity (c-statistic: .803 and .874
respectively). CONCLUSION: PD and obesity appear to synergistically increase the
risk of surgical complications. Paradoxically, malnutrition may be less easily
recognized in obese individuals and surgeons may need to more carefully evaluate
this population before surgery. Future studies should investigate therapy to
correct PD specifically among obese patients before surgery.
PMID- 25851779
TI - Adult-onset subacute sclerosing panencephalitis manifesting as slowly progressive
dementia.
PMID- 25851780
TI - Class III PI3K-mediated prolonged activation of autophagy plays a critical role
in the transition of cardiac hypertrophy to heart failure.
AB - Pathological cardiac hypertrophy often leads to heart failure. Activation of
autophagy has been shown in pathological hypertrophic hearts. Autophagy is
regulated positively by Class III phosphoinositide 3-kinase (PI3K). However, it
is unknown whether Class III PI3K plays a role in the transition of cardiac
hypertrophy to heart failure. To address this question, we employed a previously
established cardiac hypertrophy model in heat shock protein 27 transgenic mice
which shares common features with several types of human cardiomyopathy. Age
matched wild-type mice served as control. Firstly, a prolonged activation of
autophagy, as reflected by autophagosome accumulation, increased LC3 conversion
and decreased p62 protein levels, was detected in hypertrophic hearts from
adaptive stage to maladaptive stage. Moreover, morphological abnormalities in
myofilaments and mitochondria were presented in the areas accumulated with
autophagosomes. Secondly, activation of Class III PI3K Vacuolar protein sorting
34 (Vps34), as demonstrated by upregulation of Vps34 expression, increased
interaction of Vps34 with Beclin-1, and deceased Bcl-2 expression, was
demonstrated in hypertrophic hearts from adaptive stage to maladaptive stage.
Finally, administration with Wortmaninn, a widely used autophagy inhibitor by
suppressing Class III PI3K activity, significantly decreased autophagy activity,
improved morphologies of intracellular apartments, and most importantly,
prevented progressive cardiac dysfunction in hypertrophic hearts. Collectively,
we demonstrated that Class III PI3K plays a central role in the transition of
cardiac hypertrophy to heart failure via a prolonged activation of autophagy in
current study. Class III PI3K may serve as a potential target for the treatment
and management of maladaptive cardiac hypertrophy.
PMID- 25851782
TI - Poly(alpha-Peptoid)s Revisited: Synthesis, Properties, and Use as Biomaterial.
AB - Polypeptoids have been of great interest in the polymer science community since
the early half of the last century; however, they had been basically forgotten
materials until the last decades in which they have enjoyed an exciting revival.
In this mini-review, we focus on the recent developments in polypeptoid
chemistry, with particular focus on polymers synthesized by the ring-opening
polymerization (ROP) of amino acid N-carboxyanhydrides (NCAs). Specifically, we
will review traditional monomer synthesis (such as Leuchs, Katchalski, and
Kricheldorf) and recent advances in polymerization methods to yield both linear,
cyclic, and functional polymers, solution and bulk thermal properties, and
preliminary results on the use of polypeptoids as biomaterials (i.e
immunogenicity, biodistribution, degradability, and drug delivery).
PMID- 25851781
TI - Serum levels of apolipoprotein A-I and high-density lipoprotein can predict organ
failure in acute pancreatitis.
AB - INTRODUCTION: Predicting severity of pancreatitis is an important goal.
Clinicians are still searching for novel and simple biomarkers that can better
predict persistent organ failure (OF). Lipoproteins, especially high-density
lipoprotein (HDL), and apolipoprotein A-I (APO A-I), have been shown to have anti
inflammation effects in various clinical settings. Severe acute pancreatitis
(SAP) is associated with hypo-lipoproteinemia. We studied whether the
concentrations of HDL and APO A-I can predict persistent OF in patients with
predicted SAP admitted to the ICU. METHODS: In 66 patients with predicted SAP, we
prospectively evaluated the relationship between lipid levels, inflammatory
cytokines and clinical outcomes, including persistent OF and hospital mortality.
Blood samples were obtained within 24 hours of admission to the ICU. RESULTS: HDL
and APO A-I levels were inversely correlated with various disease severity
scores. Patients with persistent OF had lower levels of HDL and APO A-I, while
those with transient OF had lower levels of interleukin-6, tumor necrosis factor
alpha and lower rates of hospital mortality. Meanwhile, hospital non-survivors
had lower concentrations of HDL, and APO A-I compared to the survivors. By using
the area under the receiver operating characteristic (AUROC) curve, both HDL and
APO A-I demonstrated an excellent discriminative power for predicting persistent
OF among all patients (AUROC 0.912 and 0.898 respectively) and among those with
OF (AUROC 0.904 and 0.895 respectively). Pair-wise comparison of AUROC showed
that both HDL and APO A-I had better discriminative power than C-reactive protein
to predict persistent OF. CONCLUSIONS: Serum levels of HDL and APO A-I at
admission to the ICU are inversely correlated with disease severity in patients
with predicted SAP and can predict persistent OF in this clinical setting.
PMID- 25851783
TI - The unprecedented recurrent diploid/tetraploid mosaicism of trisomy-18
(mixoploidy; 4n+18/2n+18): clinical report.
AB - We report on a 32-year-old woman who presented at gestational age of 14 weeks.
During ultrasonographic examination, we discovered that her fetus had several
important abnormalities, including a cystic hygroma, craniofacial defects (low
set ears, broad nose), heart defects (single atrium, single ventricle), agenesis
of corpus callosum, limb defects (clenched hands, pes equinovarus). Chorionic
villus sampling and karyotyping revealed diploid/tetraploid mosaicism with
trisomy 18 (mixoploidy; 4n+18/2n+18). Her second pregnancy was terminated because
of the same clinical manifestations 1 year prior. Her first pregnancy resulted in
the birth of an entirely healthy boy. As far as know, no other similar case has
been presented in the literature.
PMID- 25851784
TI - Evaluating Ketoreductase Exchanges as a Means of Rationally Altering Polyketide
Stereochemistry.
AB - Modular polyketide synthases (PKSs) are multidomain multienzymes responsible for
the biosynthesis in bacteria of a wide range of polyketide secondary metabolites
of clinical value. The stereochemistry of these molecules is an attractive target
for genetic engineering in attempts to produce analogues exhibiting novel
therapeutic properties. The exchange of ketoreductase (KR) domains in model PKSs
has been shown in several cases to predictably alter the configuration of the
beta-hydroxy functionalities but not of the alpha-methyl groups. By systematic
screening of a broad panel of KR domains, we have identified two donor KRs that
afford modification of alpha-methyl group stereochemistry. To the best of our
knowledge, this provides the first direct in vivo evidence of KR-catalyzed
epimerization. However, none of the introduced KRs afforded simultaneous
alteration of methyl and hydroxy configurations in high yield. Therefore,
swapping of whole modules might be necessary to achieve such changes in
stereochemistry.
PMID- 25851786
TI - Rosette-forming glioneuronal tumour in a patient with multiple sclerosis.
PMID- 25851787
TI - Systemic, cerebral, and pulmonary segmental mediolytc arteriopathy: Villainous
masqueraders of vasculitis.
AB - Segmental mediolytic arteriopathy (SMA) is a newly described and uncommon variant
of arterial fibromuscular dysplasia that affects principally visceral small and
medium sized arteries. SMA is characterized by myolytic dysplasia of the arterial
media, intramural dissection, and thrombosis or ruptured aneurysms resulting in
visceral hemorrhage and infarction as the dire consequences. Because of its
relative obscurity and frequent angiographic manifestation of microaneurysms,
clinically SMA mimics polyarteritis nodosa, and the patient so diagnosed had been
treated with immunosuppressive therapy with a catastrophic outcome. Five new
cases of unsuspected SMA are described herein, three involving visceral arteries
and, for the first time, one case each affecting the cerebral and pulmonary
parenchymal arteries. Three of the five patients did not survive because SMA
remained unrecognized until after death and a subsequent review of the biopsy and
autopsy specimens. Death in each of the three patients was directly attributable
to complications of SMA or indirectly to septic complications of the
immunosuppressive therapy for the misdiagnosed vasculitis. Clinicians and
pathologists alike should become better acquainted with this unusual form of
noninflammatory arteriopathy, so as not to misdiagnose it as vasculitis.
PMID- 25851788
TI - Extensive myocytolysis as a marker of sudden cardiac death.
AB - Colliquative myocytolysis, an intracellular vacuolization of myocardial cells, is
considered an indicator of acute myocardial ischemia. Although often present in
ischemic cardiac death, this lesion is often either overlooked, or not utilized
as a criterion for diagnosing ischemia. This study reports light microscopic and
ultrastructural studies of six autopsied patients who died suddenly and showed
extensive myocytolysis as the only pathologic finding. In two of these patients,
the clinical history and electrocardiogram findings documented an acute ischemic
episode 1 to 3 hours antemortem. Six control patients with matched age and
postmortem intervals did not show the intracellular vacuolization characteristic
of myocytolysis. The postmortem intervals ranged from 2 to 12 hours.
Ultrastructurally, myocytolysis was seen as a well-defined large intracellular
vacuole without any lining membrane and associated with disrupted myofibrils,
prominent Z band degeneration, and a few fat droplets. The mitochondria showed
swelling and disruption, as well as electron dense amorphous inclusions. The
swelling and disruption of mitochondria are well-known postmortem artefacts, and
the mitochondrial amorphous inclusions, large intracellular vacuoles, prominent Z
band degeneration, and fat droplets are not seen with autolysis. We conclude that
myocytolysis, especially if extensive and restricted to an area supplied by a
major coronary artery, can be a helpful pathologic marker of myocardial ischemia,
particularly in sudden deaths without any other histologic findings.
PMID- 25851789
TI - Matrix metalloproteinases in the pathology of natural and bioprosthetic cardiac
valves.
AB - Degenerative dysfunction of cardiac valves may be accounted for by uncontrolled
extracellular matrix degradation processes in which matrix metalloproteinases
could play a major role. In this study, 24 pathologic human valves and 26
pericardial-derived bioprostheses were analysed for metalloproteinases by gelatin
zymography. Compared to controls, human stenotic valves and bioprostheses
explanted because of either calcifying or noncalcifying degeneration revealed
three notable biochemical aspects: (1) an amplification in the levels of
metalloproteinase 9 (gelatinase B), suggestive of its active role in valvular
pathology; (2) minimal modifications in the gelatinolytic levels of
metalloproteinase 2 (gelatinase A), indicative of a constitutive secretion; and
(3) activation products derived from both gelatinase A and B. All gelatinolytic
activities identified in pathologic specimens were inhibited in vitro by zinc and
calcium chelators (captopril, doxycycline, dithiothreitol, and
ethylenediaminotetraacetic acid), suggesting potential therapeutic approaches.
High levels of beta-glucuronidase (a lysosomal marker enzyme for phagocytic
cells) were found in human calcified stenotic valves and in ruptured and
calcified pericardial-derived bioprostheses. Mononuclear recruitment was minimal
to moderate in pathologic human valves, and in noncalcified ruptured
bioprostheses infiltrating mononuclear cells were concentrated in large numbers
at the cuspal free edge. These findings suggest the involvement of infiltrating
phagocytic cells and putative common mechanisms in the degeneration of both the
natural and the bioprosthetic valvular extracellular matrix (ECM).
PMID- 25851790
TI - Myocardial extramedullary hematopoiesis following myocardial infarction.
AB - Extramedullary hematopoiesis (EMH) usually accompanies a chronic hematologic
disease in adults or prematurity in neonates. We observed a striking case of EMH
in the explanted heart of a 13-year-old boy who underwent transplantation after
extensive myocardial infarction. The florid myeloid proliferation raised the
possibility of a leukemic process. To our knowledge, extensive myocardial EMH
subsequent to myocardial infarction has not been previously reported. Possible
mechanisms underlying EMH in the myocardium are presented.
PMID- 25851791
TI - Pharmacology and controlled release of hirudin for cardiovascular disorders.
AB - Hirudin is the most potent specific inhibitor of thrombin known. Hirudin was
originally isolated from leeches, but it is now also available in synthetic form
(recombinant hirudin). The inhibitor is currently undergoing clinical trials as a
potential replacement for the extensively used thrombin inhibitor heparin. In
this review, the biochemical and pharmacokinetic characteristics of hirudin
(native and recombinant) and the efficacy of hirudin in treating and preventing
cardiovascular disorders is discussed. The advantages of local controlled
delivery of hirudin for treating cardiovascular disorders are then presented.
Several implantable polymers applicable for controlled delivery system also are
introduced. Finally, the feasibility of controlled delivery of r-hirudin for
local therapy of cardiovascular disorders is addressed.
PMID- 25851792
TI - Nationwide survey of Cockayne syndrome in Japan: Incidence, clinical course and
prognosis.
AB - In the first nationwide survey of Cockayne syndrome (CS) in Japan, the incidence
of CS was estimated to be 2.77 per million births (95%CI: 2.19-3.11) and the
prevalence was approximately 1 in 2,500,000. A total of 47 CS patients (24
surviving and 23 deceased) were identified. Based on clinical course, these 47
patients were classified into CS type 1 (n = 41; 21 surviving, 20 deceased), CS
type 2 (n = 2; all deceased), CS type 3 (n = 3; all surviving), and CS/xeroderma
pigmentosum type D (n = 1, deceased). In the 41 CS type 1 patients, seven
findings (i.e. failure to thrive; photosensitivity; deafness; characteristic
facial appearance of CS [sunken eyes]; foot joint contracture; intellectual
disability; and basal ganglia calcification on computed tomography [CT]) were
observed in >90% of patients. Of these, failure to thrive, photosensitivity, and
intellectual disability (language delays) developed before 2 or 3 years of age,
whereas deafness, sunken eyes, and basal ganglia calcification on CT occurred
later. Features such as bodyweight and height stagnation, language delay,
abnormal nutritional pathways (tube feeding), and renal failure were more
prominent in the 20 deceased CS type 1 patients than in the 21 surviving CS type
1 patients. Of the 20 deceased CS type 1 patients, nine developed severe renal
failure during the terminal stages of their condition. The present findings
suggest that the clinical course of CS includes a diverse range of symptoms, but
each type has characteristic symptoms. In addition, the management of renal
failure and nutrition are very important for ensuring good quality of life
throughout the long-term course of CS.
PMID- 25851793
TI - A novel autonomous real-time position method based on polarized light and
geomagnetic field.
AB - Many animals exploit polarized light in order to calibrate their magnetic
compasses for navigation. For example, some birds are equipped with biological
magnetic and celestial compasses enabling them to migrate between the Western and
Eastern Hemispheres. The Vikings' ability to derive true direction from polarized
light is also widely accepted. However, their amazing navigational capabilities
are still not completely clear. Inspired by birds' and Vikings' ancient
navigational skills. Here we present a combined real-time position method based
on the use of polarized light and geomagnetic field. The new method works
independently of any artificial signal source with no accumulation of errors and
can obtain the position and the orientation directly. The novel device simply
consists of two polarized light sensors, a 3-axis compass and a computer. The
field experiments demonstrate device performance.
PMID- 25851794
TI - Evidence That High Catecholamine Levels Produced by Pheochromocytoma May be
Responsible for Tako-Tsubo Cardiomyopathy.
AB - Tako-tsubo cardiomyopathy (TC) is a novel form of acute heart failure,
characterized by regional left ventricular dysfunction without coronary artery
obstruction, and usually triggered by a stressful event. Excessive circulating
catecholamines have been implicated in the pathophysiology of this condition.
This report documents the unusual occurrence of acute TC events in 2 male
subjects of disparate ages, 16 and 66 years, for whom subsequent investigation in
both led to the unexpected discovery of catecholamine-producing pheochromocytoma.
Marked elevation of plasma catecholamines (epinephrine, norepinephrine, and
dopamine) was present in both subjects and were remarkably similar to those
previously reported in female patients with TC triggered by emotional stress.
These observations show a common link between TC occurrence and elevated
catecholamine levels in both male and female patients and, therefore, support the
hypothesis that excessive levels of catecholamines may be involved in the
pathophysiology of TC independent of age or gender.
PMID- 25851795
TI - Outcomes and computed tomography scan follow-up of bioresorbable vascular
scaffold for the percutaneous treatment of chronic total coronary artery
occlusion.
AB - Everolimus-eluting bioresorbable vascular scaffold (BVS) implantation in chronic
total occlusion (CTO) could provide theoretical advantages at follow-up compared
with metallic stents. This study aimed to assess the feasibility of BVS use for
the percutaneous treatment of CTO by analyzing clinical outcomes and patency at
midterm follow-up. From February 2013 to June 2014, 42 patients with 46 CTOs were
treated by BVS implantation. Once the guidewire reached the distal lumen, all the
occluded segments were predilated. Postdilation was performed in all patients. A
multislice computed tomography was scheduled for all patients at 6 months. The
mean age was 58 +/- 9 years, 41 (98%) were men and 14 (33%) diabetic. The target
vessel was predominantly the left anterior descending artery (22, 48%). According
to the Japanese-CTO score, 21 CTOs (46%) were difficult or very difficult. Most
cases were treated with an anterograde strategy (34 lesions, 74%). A hybrid
procedure with a drug-eluting stent at the distal segment was the applied
treatment in 7 CTOs (15%). The mean scaffold length was 43 +/- 21 mm. Technical
success was achieved in 45 lesions (98%), and 1 patient (2.4%) presented a non-Q
periprocedural myocardial infarction. Re-evaluation was obtained in all patients
at 6 +/- 1 months. Two re-occlusions and a focal restenosis were identified.
After 13 +/- 5 months of follow-up, there were 2 repeat revascularizations
(4.8%). Neither death nor myocardial infarction was documented. In conclusion,
BVS for CTO seems to be an interesting strategy with a high rate of technical
success and low rate of cardiac events at midterm follow-up in selected patients.
PMID- 25851796
TI - Usefulness of cardiac meta-iodobenzylguanidine imaging to identify patients with
chronic heart failure and left ventricular ejection fraction <35% at low risk for
sudden cardiac death.
AB - Patients with chronic heart failure (CHF) at risk of sudden cardiac death (SCD)
are often treated with implantable cardiac defibrillators (ICDs). However,
current criteria for device use that is based largely on left ventricular
ejection fraction (LVEF) lead to many patients receiving ICDs that never deliver
therapy. It is of clinical significance to identify patients who do not require
ICDs. Although cardiac I-123 meta-iodobenzylguanidine (MIBG) imaging provides
prognostic information about CHF, whether it can identify patients with CHF who
do not require an ICD remains unclear. We studied 81 patients with CHF and LVEF
<35%, assessed by cardiac MIBG imaging at enrollment. The heart-to-mediastinal
ratio (H/M) in delayed images and washout rates were divided into 6 grades from 0
to 5, according to the degree of deviation from control values. The study
patients were classified into 3 groups: low (1 to 4), intermediate (5 to 7), and
high (8 to 10), according to the MIBG scores defined as the sum of the H/M and
washout rate scores. Sixteen patients died of SCD during a follow-up period.
Patients with low MIBG score had a significantly lower risk of SCD than those
with intermediate and high scores (low [n = 19], 0%; intermediate [n = 37], 19%;
high [n = 25], 36%; p = 0.001). The positive predictive value of low MIBG score
for identifying patients without SCD was 100%. In conclusion, the MIBG score can
identify patients with CHF and LVEF <35% who have low risk of developing SCD.
PMID- 25851797
TI - Irregular Rhythms and Wide QRS Complexes.
PMID- 25851798
TI - Multiple biomarkers including cardiac troponins T and I measured by high
sensitivity assays, as predictors of long-term mortality in patients with chronic
renal failure who underwent dialysis.
AB - There is a high cardiac mortality in patients on long-term renal dialysis. No
studies have reported long-term outcomes relating to both high-sensitivity
cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) in
these patients. Patients who underwent long-term dialysis at the Canberra
Hospital had blood samples collected for both cardiac and other biomarkers.
Samples were stored at -80 degrees C until analysis. Mortality data were
collected at 5 years, and univariate and multivariate analyses were performed to
identify which biomarkers were predictive of mortality at 5 years. After
multivariate analysis, albumin, C-reactive protein (CRP), and hs-cTnT remained
independently predictive of all-cause mortality, with hs-cTnT having the highest
hazard ratio. If hs-cTnT was excluded from the analysis, then hs-cTnI was
independently predictive of mortality. For hs-cTnT, for both genders, the ninety
ninth percentile, derived from a population with subjects with subclinical
disease excluded, served as an excellent partition between survivors and
nonsurvivors. Receiver-operating characteristic curve analysis for hs-cTnT had
area under the curve of 0.798 and for hs-cTnI of 0.774. Kaplan-Meier curves for
the aggregation of albumin, CRP, and hs-cTnT showed a stronger predictive power
with receiver-operating characteristic area under the curve of 0.805. The
addition of echocardiographic data in an analysis of all patients who had an
echocardiogram for clinical reasons (n = 105) did not alter the final
observations in this subgroup. In conclusion, hs-cTnT retains a superior
predictive power in a dialysis-dependent population for identifying those at risk
for death and when aggregated with albumin and CRP also has substantial additive
value for identifying mortality risk in a renal-dialysis population.
PMID- 25851799
TI - National Voluntary Public Health Accreditation: Are More Local Health Departments
Intending to Take Part?
AB - OBJECTIVE: This article examines local health department (LHD) participation and
intentions to participate in national voluntary accreditation and reasons for not
seeking accreditation. Specifically, it compares the results of national surveys
among LHDs in 2010, 2013, and 2014. DESIGN: Longitudinal cohort study. SETTING:
United States. PARTICIPANTS: LHDs that responded to the 2014 Forces of Change
Survey and the 2010 and 2013 National Association of County and City Health
Officials Profile studies. MAIN OUTCOME MEASURES: LHD level of engagement in
Public Health Accreditation Board (PHAB) accreditation. RESULTS: Data of 2014
indicated that 1% of LHDs achieved accreditation and 11% had submitted an
application or a statement of intent, compared with 6% of LHDs that submitted an
application or a statement of intent in 2013. The percent of LHDs that indicated
they planned to apply for accreditation but had not submitted a statement of
intent declined from 27% in 2013 to 22% in 2014. In multivariate models,
controlling for governance category and jurisdiction population size, LHDs in
states where the state health department (SHD) participated in e-PHAB had higher
odds of being favorably inclined toward accreditation than those located in
states where the SHD was not in the e-PHAB system (odds ratio = 2.82, 95%
confidence interval: 1.81-4.41). Across 2013 and 2014, and across small and large
LHDs, the top 2 reasons for deciding not to apply for accreditation were the
time/effort required exceeded the benefits (67%) and fees were too high (46%).
CONCLUSIONS: SHDs are powerful mediators of LHDs' perceptions of the PHAB
accreditation program. Health department governance structure and jurisdiction
population size are associated with LHD accreditation participation decisions.
With the launch of PHAB's program, fewer LHDs are undecided about accreditation
participation and many have taken affirmative steps to become accredited. The top
2 reasons LHDs indicated for not proceeding with accreditation were time/effort
exceed benefit and fees perceived as too high.
PMID- 25851800
TI - Dabigatran versus warfarin major bleeding in practice: an observational
comparison of patient characteristics, management and outcomes in atrial
fibrillation patients.
AB - Data comparing the patient characteristics, management and outcomes for
dabigatran versus warfarin major bleeding in the practice setting are limited. We
performed a retrospective single health system study of atrial fibrillation
patients with dabigatran or warfarin major bleeding from October 2010 through
September 2012. Patient identification occurred through both an internal adverse
event reporting system and a structured stepwise data filtering approach using
the International Classification of Diseases diagnosis codes. Thirty-five
dabigatran major bleeding patients were identified and compared to 70 warfarin
major bleeding patients. Intracranial bleed occurred in 4.3 % of warfarin
patients and 8.6 % of dabigatran patients. Dabigatran patients tended to be older
(79.9 vs. 76 years) and were more likely to have a creatinine clearance of 15-30
mL/min (40 vs. 18.6 %, p = 0.02). Over one-third of dabigatran patients had an
excessive dose based on renal function. More dabigatran patients required a
procedure for bleed management (37.1 vs. 17.1 %, p = 0.03) and received a
hemostatic agent for reversal (11.4 vs. 1.4 %, p = 0.04). Dabigatran patients
were twice as likely to spend time in an ICU (45.7 vs. 27.1 %, p = 0.06), be
placed in hospice/comfort care (14.3 vs. 7.1 %, p = 0.24), expire during
hospitalization (14.3 vs. 7.1 %, p = 0.24), and expire within 30-days (22.9 vs.
11.4 %, p = 0.28). In a single hospital center practice setting, as compared to
warfarin, patients with dabigatran major bleeding were more likely to be older,
have renal impairment, require a procedure for bleed management and receive a
hemostatic agent. Patients with dabigatran major bleeding had an excessive dose
for renal function in more than one-third of cases.
PMID- 25851801
TI - Regarding: Ko JH, et al.: Clinical features and risk factors for development of
Bacillus bacteremia among adult patients with cancer: a case-control study. Supp
Care Cancer 2015;23(2):377-84.
PMID- 25851802
TI - Aprepitant as an add-on therapy in children receiving highly emetogenic
chemotherapy: a randomized, double-blind, placebo-controlled trial.
AB - BACKGROUND: Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5
HT-3 antagonist and dexamethasone is recommended in adults receiving moderately
and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV).
Data for use of aprepitant in children is limited and hence aprepitant is not
recommended by Pediatric Oncology Group of Ontario guidelines for prevention of
CIV in children <12 years. METHODS: A randomized, double-blind, placebo
controlled trial was conducted at a single center in chemotherapy naive children
(5-18 years) receiving highly emetogenic chemotherapy. All patients received
intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to
chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly
assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg;
41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control
group received placebo as add-on therapy. Primary outcome measure was the
incidence of acute moderate to severe vomiting, which was defined as more than
two vomiting episodes within 24 h after the administration of the first
chemotherapy dose until 24 h after the last chemotherapy dose in the block.
Complete response (CR) was defined as absence of vomiting and retching during the
specified phase. RESULTS: Of the 96 randomized patients, three were excluded from
analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm).
Acute moderate and severe vomiting was reported in 72 % patients receiving
placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response
rates during acute phase were significantly higher in aprepitant arm (48 vs. 12
%, p < 0.001). No major adverse effects were reported by patients/guardians.
CONCLUSIONS: This double-blind, randomized, placebo-controlled trial shows that
aprepitant significantly decreases the incidence of CIV during acute phase when
used as an add-on drug with ondansetron and dexamethasone in children receiving
highly emetogenic chemotherapy.
PMID- 25851803
TI - Head and neck cancer patients' perceptions of swallowing following
chemoradiotherapy.
AB - PURPOSE: The study aims to describe patients' experiences of swallowing
difficulties following (chemo)radiotherapy for head and neck cancer and to
explore any changes over time. METHODS: A purposive sample of patients with
swallowing difficulties was selected at a range of time points, from 3 to 18
months following treatment. Ethnographic observations of 12 patients were
conducted in their own homes, over a mealtime situation. Nine new patients were
interviewed about changes to their eating and drinking from pre- to post
treatment. Thematic analysis was used to code and analyse the data. RESULTS:
Patients' reports of swallowing function were divided into four time zones: pre
treatment, during radiotherapy, early (0-3 months) and late (6-18 months) time
points following treatment. The majority reported minimal problems at diagnosis,
but marked impairment during and after radiotherapy, without a return to pre
treatment functioning. The focus was on severe physical side effects and changes
to food preparation during radiotherapy and in the early phase of recovery. By 6
months, side effects began to subside, but swallowing was still difficult,
leading to major changes to family life, socialisation and lifestyle.
CONCLUSIONS: Swallowing problems after (chemo)radiotherapy are multi-faceted and
highly individualised and restrict lives in the long term. Swallowing ability may
improve in time, but does not appear to return to pre-treatment function. Further
work is required to find ways of being able to best support patients living with
this long-term condition.
PMID- 25851804
TI - The eating experience in long-term survivors of head and neck cancer: a mixed
methods study.
AB - PURPOSE: This study explored the eating experience in long-term survivors of head
and neck cancer (HNC) >=3 years post concurrent chemoradiation. Quality of life
(QOL) and the meanings and perceptions survivors had as it related to the eating
experience were explored. METHODS: Purposive sampling was utilized; 10 long-term
survivors of HNC participated in the study. A mixed-methods approach was used;
exploratory qualitative research using content analysis and summary statistics
was used to describe demographic and clinical characteristics and the Vanderbilt
Head and Neck Symptom Survey version 2.0 scores (VHNSS 2.0). RESULTS: Four
categories (psychological, social impact, functional status, and the current
eating experience) containing 15 subthemes and 1 overarching theme (adaptation)
emerged. Current health status, QOL, and QOL related to eating were viewed
favorably despite the impact of treatment late effects on participants' daily
lives. Adaptation and maladaptation in regard to food choice and downplaying of
symptoms were recognized. Interviews as well as the VHNSS 2.0 scores indicated
that xerostomia, mucosal sensitivity, swallowing difficulty, length of time
required to eat, and dysgeusia remained problematic. CONCLUSION: Psychological,
functional, and social losses associated with eating were identified.
Participants modify or avoid foods that are challenging yet report enjoyment with
eating. Challenges with eating were downplayed. Due to the potential negative
nutritional and social implications of avoiding specific food/food groups,
standard of care in long-term survivors of HNC should include assessment of the
eating experience and functional challenges. Nutrition professional can help
patients optimize dietary intake and the eating experience.
PMID- 25851805
TI - Developmental trajectories for attention and working memory in healthy Japanese
school-aged children.
AB - OBJECTIVE: The aim of this study was to investigate the developmental
trajectories of attention, short-term memory, and working memory in school-aged
children using a 10 min test battery of cognitive function. METHODS: Participants
comprised 144 typically developing children (TDC) aged 7-12 years and 24 healthy
adults, divided according to age into seven groups (12 males and 12 females for
each age group). Participants were assessed using CogHealth, which is a computer
based measure composed of five tasks. We measured attention, short-term memory,
and working memory (WM) with visual stimulation. Each task was analyzed for age
related differences in reaction time and accuracy rate. RESULTS: Attention tasks
were faster in stages from the age of 7-10 years. Accuracy rate of short-term
memory gradually increased from 12 years of age and suddenly increased and
continued to increase at 22 years of age. Accuracy rate of working memory
increased until 12 years of age. Correlations were found between the ages and
reaction time, and between ages and accuracy rate of the tasks. CONCLUSION: These
results indicate that there were rapid improvements in attention, short-term
memory, and WM performance between 7 and 10 years of age followed by gradual
improvement until 12 years of age. Increase in short-term memory continued until
22 years of age. In our experience CogHealth was an easy and useful measure for
the evaluation of cognitive function in school-age children.
PMID- 25851806
TI - Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5
oxoprolinase deficiencies.
AB - OBJECTIVE: 5-Oxoprolinuria is a rare inherited metabolic disorder caused by a
defective gamma-glutamyl cycle resulting from mutations in the genes encoding 5
oxoprolinase (OPLAH) and glutathione synthetase (GSS). No inherited 5
oxoprolinuria case has been reported in mainland China until now. In this study,
clinical, biochemical, and genetic aspects of five Chinese 5-oxoprolinuria
patients with OPLAH or GSS gene mutations were investigated. METHODS: Three boys
and two girls from five unrelated Chinese families with symptomatic 5
oxoprolinuria were identified within the past 3years in Peking University First
Hospital. OPLAH and GSS genes were analyzed. RESULTS: Patients were hospitalized
between the age of 13days to 1year and 3months for hypersomnia, developmental
retardation, feeding deficiency, vomiting, icterus and recurrent pneumonia. All
patients had significantly elevated urine 5-oxoproline. Three novel mutations
(c.1904G>A and c.2813_2815delGGG in Patient 1, c.2978G>T in Patient 2) on OPLAH,
on GSS, one novel mutation (c.1252C>T in Patient 3) and a reported mutation
(c.491G>A in Patients 3-5) were detected. Patient 4 has homozygous mutation
c.491G>A, the others are heterozygous. After treatment by l-carnitine, vitamin E,
B1, B2 and coenzyme Q10, three patients with GSS deficiency improved, but the two
5-oxoprolinase-deficient patients did not respond to treatment. CONCLUSIONS: 5
Oxoprolinase deficiency and GSS deficiency share some clinical and biochemical
features. Genetic analysis is important for the deferential diagnosis. In this
study, five Chinese patients had severe central nervous system damage.
Antioxidant treatments were proved effective for the three patients with GSS
deficiency but not for the two patients with 5-oxoprolinase deficiency.
PMID- 25851807
TI - Aerobic sludge granulation at high temperatures for domestic wastewater
treatment.
AB - With inoculum sludge from a conventional activated sludge wastewater treatment
plant, three sequencing batch reactors (SBRs) fed with synthetic wastewater were
operated at different high temperatures (30, 40 and 50+/-1 degrees C) to study
the formation of aerobic granular sludge (AGS) for simultaneous organics and
nutrients removal with a complete cycle time of 3h. The AGS were successfully
cultivated with influent loading rate of 1.6CODg(Ld)(-1). The COD/N ratio of the
influent wastewater was 8. The results revealed that granules developed at 50
degrees C have the highest average diameter, (3.36mm) with 98.17%, 94.45% and
72.46% removal efficiency observed in the system for COD, ammonia and phosphate,
respectively. This study also demonstrated the capabilities of AGS formation at
high temperatures which is suitable to be applied for hot climate conditions.
PMID- 25851808
TI - Therapeutic plasma exchange as a steroid-sparing therapy in a patient with limbic
encephalitis due to antibodies to voltage-gated potassium channels.
AB - Autoantibodies to the voltage-gated potassium channel (VGKC) complex cause a
spectrum of non-paraneoplastic neurologic syndromes including limbic encephalitis
(LE). We report a case of a man with LE who underwent a course of therapeutic
plasma exchange (TPE) in addition to other immunomodulatory therapies and
experienced sustained clinical resolution of his symptoms. This report adds to
the existing literature supporting TPE in cases of LE due to VGKC complex
autoantibodies.
PMID- 25851809
TI - First report of inhibitory von Willebrand factor alloantibodies in type 2B von
Willebrand disease.
PMID- 25851811
TI - Cyst infection in autosomal dominant polycystic kidney disease: causative
microorganisms and susceptibility to lipid-soluble antibiotics.
AB - Cyst infection is a frequent and serious complication of autosomal dominant
polycystic kidney disease (ADPKD). Lipid-soluble antibiotics like
fluoroquinolones show good penetration into cysts and are recommended for cyst
infection, but causative microorganisms are often resistant to these agents. This
study investigated the profile of the microorganisms causing cyst infection in
ADPKD, their susceptibility to lipid-soluble antibiotics, and clinical outcomes.
This retrospective study reviewed all ADPKD patients admitted to Toranomon
Hospital with a diagnosis of cyst infection from January 2004 to March 2014. All
patients who underwent cyst drainage and had positive cyst fluid cultures were
enrolled. Patients with positive blood cultures who satisfied our criteria for
cyst infection or probable infection were also enrolled. There were 99 episodes
with positive cyst fluid cultures and 93 episodes with positive blood cultures.
The majority of patients were on dialysis. The death rate was high when infection
was caused by multiple microorganisms or when there were multiple infected cysts.
Gram-negative bacteria accounted for 74-79 % of the isolates in all groups,
except for patients with positive hepatic cyst fluid cultures. The susceptibility
of Escherichia coli to fluoroquinolones was very low in patients with hepatic
cyst infection, especially those with frequent episodes and those with
hepatomegaly. Fungi were detected in two episodes. Fluoroquinolone-resistant
microorganisms showed a high prevalence in cyst infection. It is important to
identify causative microorganisms to avoid the overuse of fluoroquinolones and to
improve the outcome of cyst infection in ADPKD.
PMID- 25851810
TI - The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling.
AB - The c-Jun/AP-1 transcription factor controls key cellular behaviours, including
proliferation and apoptosis, in response to JNK and Ras/MAPK signalling. While
the JNK pathway has been well characterized, the mechanism of activation by Ras
was elusive. Here we identify the uncharacterized ubiquitin ligase Trim7 as a
critical component of AP-1 activation via Ras. We found that MSK1 directly
phosphorylates Trim7 in response to direct activation by the Ras-Raf-MEK-ERK
pathway, and this modification stimulates Trim7 E3 ubiquitin ligase activity.
Trim7 mediates Lys63-linked ubiquitination of the AP-1 co-activator RACO-1,
leading to RACO-1 protein stabilization. Consequently, Trim7 depletion reduces
RACO-1 levels and AP-1-dependent gene expression. Moreover, transgenic
overexpression of Trim7 increases lung tumour burden in a Ras-driven cancer
model, and knockdown of Trim7 in established xenografts reduces tumour growth.
Thus, phosphorylation-ubiquitination crosstalk between MSK1, Trim7 and RACO-1
completes the long sought-after mechanism linking growth factor signalling and AP
1 activation.
PMID- 25851812
TI - Design and validation of a qPCR assay for accurate detection and initial
serogrouping of Legionella pneumophila in clinical specimens by the ESCMID Study
Group for Legionella Infections (ESGLI).
AB - Prompt detection of Legionella pneumophila is essential for rapid investigation
of legionellosis. Furthermore, as the majority of L. pneumophila infections are
caused by serogroup 1 (sg1) strains, rapid identification of such strains can be
critical in both routine and outbreak scenarios. The ESCMID Study Group for
Legionella Infections (ESGLI) was established in 2012 and immediately identified
as a priority the validation of a reliable, easy to perform and interpret, cost
effective qPCR assay to standardise the detection of L. pneumophila DNA amongst
members. A novel L. pneumophila assay targeting the mip gene was designed and
combined with previously published methodologies amplifying the sg1 marker (wzm)
and the green fluorescent protein gene (gfp) internal process control. The
resulting triplex assay was validated internationally on the three qPCR platforms
used by the majority of European Legionella reference laboratories: ABI 7500
(Life Technologies), LightCycler 480 Instrument II (Roche) and Rotor-Gene Q
(Qiagen). Clinical and EQA specimens were tested together with a large panel of
strains (251 in total) to validate the assay. The assay proved to be 100%
specific for L. pneumophila and sg1 DNA both in silico and in vitro. Efficiency
values for mip and wzm assays ranged between 91.97 and 97.69%. Limit of detection
values estimated with 95% confidence were adopted for mip and wzm assays on all
three qPCR platforms. Inhibition was not observed. This study describes a robust
assay that could be widely implemented to standardise the molecular detection of
L. pneumophila among ESGLI laboratories and beyond.
PMID- 25851813
TI - Spontaneous Parahisian Accessory Pathway Activity.
PMID- 25851816
TI - From bacteria to mollusks: the principles underlying the biomineralization of
iron oxide materials.
AB - Various organisms possess a genetic program that enables the controlled formation
of a mineral, a process termed biomineralization. The variety of biological
material architectures is mind-boggling and arises from the ability of organisms
to exert control over crystal nucleation and growth. The structure and
composition of biominerals equip biomineralizing organisms with properties and
functionalities that abiotically formed materials, made of the same mineral,
usually lack. Therefore, elucidating the mechanisms underlying biomineralization
and morphogenesis is of interdisciplinary interest to extract design principles
that will enable the biomimetic formation of functional materials with similar
capabilities. Herein, we summarize what is known about iron oxides formed by
bacteria and mollusks for their magnetic and mechanical properties. We describe
the chemical and biological machineries that are involved in controlling mineral
precipitation and organization and show how these organisms are able to form
highly complex structures under physiological conditions.
PMID- 25851818
TI - Impact of early haemodynamic goal-directed therapy in patients undergoing
emergency surgery: an open prospective, randomised trial.
AB - Haemodynamic goal-directed therapies (GDT) may improve outcome following elective
major surgery. So far, few data exist regarding haemodynamic optimization during
emergency surgery. In this randomized, controlled trial, 50 surgical patients
with hypovolemic or septic conditions were enrolled and we compared two
algorithms of GDTs based either on conventional parameters and pressure pulse
variation (control group) or on cardiac index, global end-diastolic volume index
and stroke volume variation as derived from the PiCCO monitoring system
(optimized group). Postoperative outcome was estimated by a composite index
including major complications and by the Sequential Organ Failure Assessment
(SOFA) Score within the first 3 days after surgery (POD1, POD2 and POD3). Data
from 43 patients were analyzed (control group, N = 23; optimized group, N = 20).
Similar amounts of fluid were given in the two groups. Intraoperatively,
dobutamine was given in 45 % optimized patients but in no control patients. Major
complications occurred more frequently in the optimized group [19 (95 %) versus
10 (40 %) in the control group, P < 0.001]. Likewise, SOFA scores were higher in
the optimized group on POD1 (10.2 +/- 2.5 versus 6.6 +/- 2.2 in the control
group, P = 0.001), POD2 (8.4 +/- 2.6 vs 5.0 +/- 2.4 in the control group, P =
0.002) and POD 3 (5.2 +/- 3.6 and 2.2 +/- 1.3 in the control group, P = 0.01).
There was no significant difference in hospital mortality (13 % in the control
group and 25 % in the optimized group). Haemodynamic optimization based on
volumetric and flow PiCCO-derived parameters was associated with a less favorable
postoperative outcome compared with a conventional GDT protocol during emergency
surgery.
PMID- 25851819
TI - Metabolic activation of furan moiety makes Diosbulbin B hepatotoxic.
AB - Diosbulbin B (DIOB), a furanoid, is a major constituent of herbal medicine
Dioscorea bulbifera L. Exposure to DIOB caused liver injury in humans and
experimental animals. The mechanisms of DIOB-induced hepatotoxicities remain
unknown. The present study demonstrated that DIOB induced hepatotoxicities in a
time- and dose-dependent manner in mice. H&E stained histopathologic image showed
the occurrence of necrosis in the liver obtained from the mice treated with DIOB
at dose of 200 mg/kg. Pretreatment with KTC protected the animals from
hepatotoxicities and hepatic GSH depletion induced by DIOB, increased area under
the concentration-time curve of blood DIOB, decreased urinary excretion of GSH
conjugates derived from DIOB, and increased urinary excretion of parent drug.
Pretreatment with BSO exacerbated DIOB-induced hepatotoxicities. In order to
define the role of furan moiety in DIOB-induced liver toxicities, we replaced the
furan of DIOB with a tetrahydrofuran group by chemical hydrogenation of the furan
ring of DIOB. No liver injury was observed in the animals given the same doses of
tetrahydro-DIOB. The furan moiety was essential for DIOB-induced
hepatotoxicities. The results implicate the cis-enedial reactive metabolite of
DIOB was responsible for the observed toxicities. The observed modest depletion
of hepatic GSH in DIOB-treated animals suggests the actions of one or more
reactive metabolites, and the hepatic injury observed could be due at least in
part to reactions of these metabolites with crucial biomolecules. Cytochrome P450
3A enzymes are implicated in DIOB-induced hepatotoxicities by catalyzing the
formation of the reactive metabolite of DIOB.
PMID- 25851820
TI - From smoking guns to footprints: mining for critical events of toxicity pathways
in transcriptome data.
PMID- 25851822
TI - Developing tools for defining and establishing pathways of toxicity.
PMID- 25851821
TI - MPTP's pathway of toxicity indicates central role of transcription factor SP1.
AB - Deriving a Pathway of Toxicity from transcriptomic data remains a challenging
task. We explore the use of weighted gene correlation network analysis (WGCNA) to
extract an initial network from a small microarray study of MPTP toxicity in
mice. Five modules were statistically significant; each module was analyzed for
gene signatures in the Chemical and Genetic Perturbation subset of the Molecular
Signatures Database as well as for over-represented transcription factor binding
sites and WGCNA clustered probes by function and captured pathways relevant to
neurodegenerative disorders. The resulting network was analyzed for transcription
factor candidates, which were narrowed down via text-mining for relevance to the
disease model, and then combined with the large-scale interaction FANTOM4
database to generate a genetic regulatory network. Modules were enriched for
transcription factors relevant to Parkinson's disease. Transcription factors
significantly improved the number of genes that could be connected in a given
component. For each module, the transcription factor that had, by far, the
highest number of interactions was SP1, and it also had substantial experimental
evidence of interactions. This analysis both captures much of the known biology
of MPTP toxicity and suggests several candidates for further study. Furthermore,
the analysis strongly suggests that SP1 plays a central role in coordinating the
cellular response to MPTP toxicity.
PMID- 25851824
TI - Jejunal Intussusception in Peutz-Jeghers Syndrome Mimicking Acute Appendicitis.
PMID- 25851823
TI - Tuberculous Epididymitis: A Case of Tuberculous Epididymitis That Was the
Presenting Manifestation of Extrapulmonary and Pulmonary Tuberculoses.
PMID- 25851825
TI - Cystic Adventitial Disease.
PMID- 25851826
TI - Bodily pain intensity in nursing home residents with pressure ulcers: analysis of
national minimum data set 3.0.
AB - Clinical reports suggest that superficial pressure ulcers produce pain, but that
pain decreases as the wound advances in stage. This study of the relationship
between pressure ulcer stage and bodily pain intensity in nursing home residents
was a secondary analysis of the national Minimum Data Set 3.0 assessment data in
long-term care facilities, collected from nursing home residents at least 65
years of age. Data were examined from residents with pressure ulcers who
completed a bodily pain intensity interview between January and March 2012 (N =
41,680) as part of the MDS comprehensive assessment. After adjusting for other
variables (e.g., cognition, functional impairment, presence of comorbidities, use
of scheduled pain medication, and sociodemographic variables), bodily pain
intensity for those with more severe pressure ulcers in comparison to those with
Stage I ulcers was higher by 11% (Stage II), 14% (Stage III), 24% (Stage IV), and
22% (suspected deep tissue injury). Because multivariate analysis showed that
greater bodily pain intensity was associated with an advanced stage of pressure
ulcer, health care providers should assess bodily pain intensity and order
appropriate pain management for nursing home residents with pressure ulcers,
particularly for those with advanced pressure ulcers who are vulnerable to
greater bodily pain intensity.
PMID- 25851827
TI - Identification of a novel TMEM106B-ROS1 fusion variant in lung adenocarcinoma by
comprehensive genomic profiling.
AB - OBJECTIVES: ROS1-rearranged non-small cell lung cancer (NSCLC) is a unique
molecularly defined yet heterogeneous subset of NSCLC. To date 12 known fusion
partners of ROS1 in NSCLC have been reported. While crizotinib, a multi-targeted
ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has demonstrated significant
clinical activity in ROS1-rearranged NSCLC, no companion diagnostic assay has
been approved for the detection of ROS1-rearrange NSCLC by the US FDA.
Comprehensive genomic profiling (CGP), a subtype of clinical next-generation
sequencing (NGS), offers a uniquely comprehensive and convenient approach to
detect the ever-increasing and "druggable" receptor-kinase rearrangements being
discovered in lung cancer. MATERIALS AND METHODS: We identified a novel ROS1
fusion variant (TMEM106B-ROS1) in a stage IV adenocarcinoma of the lung never
smoker female patient during routine genomic profiling (FoundationOne). This
novel TMEM106B-ROS1 fusion variant is generated by the fusion of exons 1-3 of
TMEMB106B on chromosome 7p21 to the exons 35-43 of ROS1 on chromosome 6q22. The
predicted TMEM106-ROS1 protein product contains 540 amino acids comprising of the
N-terminal amino acids 1-73 of TMEMB106 and C-terminal amino acids of 1881-2341
of ROS1. Although there is no predicted "coiled-coil" domain in the N-terminal
domain of TMEM106B, the N-terminal domain of TMEM106B is involved in homo- and
hetero-dimerization with other TMEM106 family members. CONCLUSIONS: TMEM106B-ROS1
is a novel ROS1 fusion variant in NSCLC identified by comprehensive genomic
profiling and should be included in any ROS1 detecting assay that depends on
identifying the corresponding fusion partners such as reverse transcriptase
polymerase chain reaction (RT-PCR).
PMID- 25851828
TI - Do sleep complaints predict persistent fatigue in older adults?
AB - OBJECTIVES: To examine the association between sleep complaints, use of sleep
promoting medications, and persistent severe fatigue (PSF). DESIGN: Analysis of
data from the National Health Aging Trends Study. SETTING: Contiguous United
States. PARTICIPANTS: A representative sample of Medicare beneficiaries aged 65
and older. MEASUREMENTS: Difficulty initiating sleep, difficulty staying asleep,
use of sleep-promoting medications, demographic characteristics, presence of
pain, use of pain medications, depression, chronic medical disease, physical
activity level, and Short Physical Performance Battery score measured at
baseline. The outcome of interest was PSF (fatigue that limits daily activities
reported at baseline and 12-month follow-up). RESULTS: Of 8,245 participants at
baseline, 7,075 completed 12-month follow-up; 31% reported severe fatigue at
baseline and 31% at follow-up, and 19% reported PSF. In a logistic regression
model, difficulty staying asleep some nights (odds ratio (OR) = 1.32, 95%
confidence interval (CI) = 1.08-1.60) and most nights or every night (OR = 1.40,
95% CI = 1.09-1.79) and use of sleep-promoting medications most nights or every
night (OR = 1.35, 95% CI = 1.08-1.67) independently predicted PSF. CONCLUSION:
The results indicate greater risk of PSF in older adults with difficulty staying
asleep and those who use sleep-promoting medications. These findings underscore
the significance of sleep problems and present potential targets for
interventional studies that aim to improve fatigue in older adults.
PMID- 25851829
TI - Increased risk of second primary malignancy in pediatric and young adult patients
treated with radioactive iodine for differentiated thyroid cancer.
AB - INTRODUCTION: The long-term sequelae of radioactive iodine (RAI) for
differentiated thyroid cancer (DTC) in pediatric and young adult patients are not
well-defined. Epidemiologic analyses of second primary malignancy (SPM) risk have
only been performed in the adult population. Existing data are limited to case
series with limited follow-up. The objective of this study was to analyze the
elevated risk of SPM attributable to RAI in young patients treated for DTC.
METHODS: Population-based analysis of 3850 pediatric and young adult patients
(<25 years old) undergoing treatment with surgery with/without RAI for DTC,
followed in the Surveillance, Epidemiology, and End Results cancer registry (1973
2008), equating to 54,727 person-years at risk (PYR). The excess risk of SPM was
calculated relative to a reference population and expressed as standardized
incidence ratio (SIR) and excess absolute risk (EAR) per 10,000 PYR. Excess risk
was compared in RAI-treated and non-RAI-treated patients. RESULTS: A total of
1571 patients (40%) received RAI. The percentage of patients treated with RAI
increased over time, from 4% in 1973 to 62% in 2008 (p<0.001). Among patients who
received RAI, 26 SPMs were observed, and 18.3 were expected. The relative risk of
SPM at any site was significantly elevated (SIR=1.42), corresponding to 4.4
excess cases per 10,000 PYR. SPM risk was not elevated in the non-RAI-treated
cohort (SIR=1.01, EAR=0). Patients treated with RAI were at dramatically elevated
risk for development of a salivary malignancy (SIR=34.1), corresponding to 1.7
excess cases per 10,000 PYR. The risk of leukemia in RAI-treated patients was
elevated (SIR=4.0, EAR=0.9) but did not reach statistical significance. There was
no elevated risk of salivary cancer or leukemia in the non-RAI-treated cohort.
CONCLUSIONS: Pediatric and young adult patients who receive RAI for DTC
experience an elevated risk of SPM, mainly salivary gland cancer. These risks
appear to be only slightly higher than in adult patients. Over a decade,
approximately 1 in 227 RAI-treated patients will develop an SPM, and 1 in 588 RAI
treated patients will develop a salivary cancer, attributable to RAI. Because the
expected survival time for young DTC patients is long, it is critical to weigh
the benefits of RAI carefully against the small, but real, increase in SPM risk.
PMID- 25851830
TI - Prediabetes, diagnosed and undiagnosed diabetes, their risk factors and
association with knowledge of diabetes in rural Bangladesh: The Bangladesh
Population-based Diabetes and Eye Study.
AB - BACKGROUND: The aim of the present study was to determine the prevalence and risk
factors of prediabetes and diagnosed and undiagnosed diabetes mellitus (DM) in
rural Bangladesh. METHODS: Using a population-based cluster random sampling
strategy, 3104 adults aged >=30 years were recruited. Fasting capillary blood
glucose, blood pressure, height, weight, waist circumference, and knowledge,
attitudes, and practice related to diabetes were recorded. Diabetes was defined
as fasting glucose (FG) >=7.0 mmol/L or a self-reported diagnosis of diabetes;
impaired FG (IFG) was defined as FG >= 6.1 and <7.0 mmol/L. RESULTS: The overall
crude prevalence of DM was 7.2% (95% confidence interval [CI] 6.3%-8.1%; n =
222), of which 55% (n = 123) was previously undiagnosed (UDM). The prevalence of
IFG was 5.3% (95% CI 4.5%-6.1%; n = 163). The age-standardized prevalence of DM
and IFG was 6.6% and 5.0%, respectively. The prevalence of UDM was higher in
people of lower socioeconomic status (59% vs. 31%; P < 0.001). Of those with
known DM, 56% had poor glycemic control (FG >= 7.0 mmol/L) and 37% were not on
medication. Overall knowledge of DM was poor; only 16.3%, 17.8%, and 13.4% of
those with UDM, IFG, and normal FG knew that diabetes causes eye disease,
compared with 55.6% of those with known DM (Ptrend < 0.001). CONCLUSIONS: In
this rural Bangladeshi community, UDM was high. Lower socioeconomic status was
associated with a higher risk of UDM. Overall knowledge of DM was poor. Public
health programmes should target those of low socioeconomic status and aim to
increase knowledge of DM in rural Bangladesh.
PMID- 25851831
TI - Synthesis, characterization and gas sensing properties of novel homo and hetero
dinuclear ball-type phthalocyanines.
AB - New ball-type homodinuclear Co(ii)-Co(ii) phthalocyanine () and ball-type
heterodinuclear Co(ii)-Fe(ii) phthalocyanine () were synthesized from the
corresponding [2,10,16,24-tetrakis{4,4'-cyclohexylidenebis(2
cyclohexyphenoxyphthalonitrile)}phthalocyaninatocobalt(ii)] (). The novel
compounds have been characterized by elemental analysis, IR, UV-Vis and MALDI-TOF
mass spectroscopy. Gas sensing capability of the spin coated film of and were
studied using amperometric technique at various temperatures. For a better
understanding of the interaction of and films with organic compounds, two
different groups of compounds (aromatics and alcohols) were selected as test
analytes. It was observed that the operating temperature had a considerable
effect on the gas sensing performance of the sensors investigated. The
experimental results show that film offers a promising perspective as a sensing
material for the detection of relatively low aromatic vapours even at room
temperature. This suggests that aromatics might be distinguished from alcohols.
The obtained data were analysed using two different adsorption kinetic models:
the pseudo first order equation and Elovich equation to determine the best fit
equation for the adsorption of toluene vapor onto and films. The first-order
equation was the best of the various kinetic models studied to describe the
adsorption kinetic of toluene on Pc films at higher concentrations, as evidenced
by the highest correlation coefficients. In addition, it was observed that
Elovich equation generates a straight line that best fit to the data of
adsorption of lower concentrations of toluene.
PMID- 25851832
TI - Surface-based chondroblastoma of the tibia: a unique presentation.
AB - BACKGROUND: Chondroblastoma is a benign tumor classically located within the
epiphysis of the long bones. The tumor is believed to arise from immature cells
of the epiphyseal plate. Purely metaphyseal or diaphyseal chondroblastoma is
exceedingly uncommon, occurring in approximately 2% of chondroblastoma cases. In
all of these non-epiphyseal-based cases, the tumor has been intramedullary.
METHODS: We describe the histologic and imaging features of the first detailed
description of a surface-based chondroblastoma. RESULTS: The tumor was located in
the anteromedial midshaft of the tibia in a 47-year-old male. CONCLUSION: We
discuss the diagnostic considerations and possible etiology of chondroblastoma
given this unusual location.
PMID- 25851834
TI - Antifeedant activity of xanthohumol and supercritical carbon dioxide extract of
spent hops against stored product pests.
AB - Xanthohumol, a prenylated flavonoid from hops, and a supercritical carbon dioxide
extract of spent hops were studied for their antifeedant activity against stored
product insect pests: Sitophilus granarius L., Tribolium confusum Duv. and
Trogoderma granarium Everts. Xanthohumol exhibited medium deterrent activity
against the adults of S. granarius L. and larvae of T. confusum Duv. The spent
hops extract was more active than xanthohumol towards the adults of T. confusum
Duv. The potential application of the crude spent hops extract as a feeding
deterrent against the stored product pests is proposed.
PMID- 25851837
TI - The development of modern approaches to aphasia: a concise overview.
AB - The aim of this article is to review the rationale on which modern aphasia test
batteries are based. Since the mid-1950s, a starting point chosen because the
discipline of speech (language) pathology was created during that period, a
corpus of English aphasia tests was identified through searches of electronic
databases. The tests were critically evaluated in terms of their theoretical
roots and influences. During the past 50 years, the fundamentals of aphasia
assessment remained basically unchanged, that is, to identify and gain insight
into the nature and the degree of a language disturbance. However, the way in
which the assessment has taken place has shifted back and forth from a purely
medical approach to a more neurolinguistic or social approach depending on the
influence exerted by different scientific fields. Not a single model on which
aphasia assessments rely covers the many and multifaceted problems of individuals
with aphasia. At several points in time during the rehabilitation process, the
clinician and the patient will encounter a crossroad, where it has to be decided
which path to follow next and how to evaluate the covered path. Besides
application of formal test batteries, observations in different natural settings,
evaluations of functional communication and insights into psychosocial coping
contribute towards a holistic approach to aphasia.
PMID- 25851835
TI - Lentibacillus garicola sp. nov., isolated from myeolchi-aekjeot, a Korean
fermented anchovy sauce.
AB - A Gram-stain positive, aerobic and moderately halophilic bacterium, designated
strain SL-MJ1(T), was isolated from myeolchi-aekjeot, a Korean traditionally
fermented anchovy sauce. Cells were observed to be non-spore-forming rods showing
oxidase-negative and catalase-positive reactions. Growth of strain SL-MJ1(T) was
observed at 15-40 degrees C (optimum, 30 degrees C) and pH 6.5-8.0 (optimum, pH
7.0) and in the presence of 0-20 % (w/v) NaCl (optimum, 6 %). Chemotaxonomic data
(major isoprenoid quinone: menaquinone-7; DNA G + C content: 42.8 mol%; cell wall
type: meso-diaminopimelic acid; major fatty acids: anteiso-C15:0, anteiso-C17:0
and iso-C16:0) support the affiliation of the isolate to the genus Lentibacillus.
Phosphatidylglycerol, diphosphatidylglycerol and an unidentified phospholipid
were identified as the major cellular polar lipids. Comparative 16S rRNA gene
sequence analysis showed that strain SL-MJ1(T) is most closely related to
Lentibacillus juripiscarius IS40-3(T) with a 95.3 % similarity. Phylogenetic
analysis based on 16S rRNA gene sequences also support the conclusion that strain
SL-MJ1(T) forms a phylogenetic lineage with members of the genus Lentibacillus
within the family Bacillaceae. Given its phylogenetic, phenotypic and
chemotaxonomic features, we conclude that strain SL-MJ1(T) represents a novel
species of the genus Lentibacillus, for which the name Lentibacillus garicola sp.
nov. is proposed. The type strain is SL-MJ1(T) (=KACC 18130(T) = JCM 30131(T)).
PMID- 25851838
TI - Development and validity of the Outdoor Falls Questionnaire.
AB - The aim of this study was to develop and examine the content and face validity of
the Outdoor Falls Questionnaire. The initial questionnaire was developed by the
primary investigator on the basis of the existing literature on outdoor falls. A
rating scale was used to obtain feedback from content experts to ascertain the
validity of each question and the questionnaire as a whole. Cognitive
interviewing of community-dwelling seniors was performed to ensure accurate
interpretation of each question. An expert in questionnaire design reviewed the
questions for language and structure. Content experts rated the questionnaire as
a whole as 'quite relevant' or 'very relevant' to outdoor falls. The majority of
individual questions (22 of 32) were rated by experts as either quite relevant or
very relevant. Feedback from reviewers and older adults on specific questions
were incorporated into the revised questionnaire. Preliminary testing
demonstrates that the Outdoor Falls Questionnaire has good content and face
validity. Further testing is needed to examine factor structure, to establish
reliability, internal consistency, and interclass correlations.
PMID- 25851836
TI - Sporadic Creutzfeldt-Jakob Disease MM1+2C and MM1 are Identical in Transmission
Properties.
AB - The genotype (methionine, M or valine, V) at polymorphic codon 129 of the PRNP
gene and the type (1 or 2) of abnormal prion protein in the brain are the major
determinants of the clinicopathological features of sporadic Creutzfeldt-Jakob
disease (CJD), thus providing molecular basis for classification of sporadic CJD,
that is, MM1, MM2, MV1, MV2, VV1 or VV2. In addition to these "pure" cases,
"mixed" cases presenting mixed neuropathological and biochemical features have
also been recognized. The most frequently observed mixed form is the co
occurrence of MM1 and MM2, namely MM1+2. However, it has remained elusive whether
MM1+2 could be a causative origin of dura mater graft-associated CJD (dCJD), one
of the largest subgroups of iatrogenic CJD. To test this possibility, we
performed transmission experiments of MM1+2 prions and a systematic
neuropathological examination of dCJD patients in the present study. The
transmission properties of the MM1+2 prions were identical to those of MM1 prions
because MM2 prions lacked transmissibility. In addition, the neuropathological
characteristics of MM2 were totally absent in dCJD patients examined. These
results suggest that MM1+2 can be a causative origin of dCJD and causes
neuropathological phenotype similar to that of MM1.
PMID- 25851839
TI - Synergism of antioxidant action of vitamins E, C and quercetin is related to
formation of molecular associations in biomembranes.
AB - Vitamins E, C and polyphenols (flavonoids and non-flavonoids) are major natural
antioxidants capable of preventing damage generated by oxidative stress. Here we
show the capacity of these antioxidants to form non-covalent association within
lipid bilayers close to the membrane/cytosol interface. Antioxidant regeneration
is significantly enhanced in these complexes.
PMID- 25851840
TI - Does albuminuria correlate with silent myocardial ischemia and delayed heart rate
recovery in hypertensive men without diabetes mellitus.
AB - BACKGROUND: In diabetes patients, albuminuria has been proven to be an
independent predictor for SMI and delayed heart rate recovery (HRR). However, in
hypertensive patients without diabetes the correlation is still unclear. AIM: To
determine the correlation between albuminuria to SMI and delayed HRR in
hypertensive patients without diabetes. METHODS: Fourty consecutive asymptomatic
primary hypertensive men, aged 40-60 years, without diabetes were included. They
underwent treadmill stress testing (TST) and collection of spot urine to measure
albumin urine to creatinine ratio (ACR). SMI and HRR at first, second, and third
minute were then recorded. SMI was diagnosed if positive ischemic criteria of TST
was met without anginal symptom. Albuminuria and delayed HRR were diagnosed based
on the treshold value respectively. RESULTS: SMI was diagnosed in 15 % patients.
The prevalence of delayed HRR at the first-, second-, and third-minute after
exercise were 60, 80, and 52.5 % respectively. Albuminuria was significantly
associated with SMI [OR 13.889 (95 % CI 1.423-135.544), p = 0.014]. ROC curve
analysis demonstrated the area under the curve (AUC) = 0.784 [(95 % CI 0.588
0.98), p = 0.028], with subsequent calculated sensitivity, specificity, positive-
and negative-predictive value of albuminuria to predict SMI were 83.3, 73.5,
35.7, and 96.2 % respectively. Those were no significant correlation between
albuminuria and delayed HRR at first, second, and third minute. CONCLUSION:
Albuminuria is a potential marker for excluding SMI in asymptomatic hypertensive
men without diabetes.
PMID- 25851842
TI - Efficacy of communication skills training on colorectal cancer screening by GPs:
a cluster randomised controlled trial.
AB - Colorectal cancer (CRC) mass screening has been implemented in France since 2008.
Participation rates remain too low. The objective of this study was to test if
the implementation of a training course focused on communication skills among
general practitioners (GP) would increase the delivery of gaiac faecal occult
blood test and CRC screening participation among the target population of each
participating GP. A cluster randomised controlled trial was conducted with GP's
practice as a cluster unit. GPs from practices in the control group were asked to
continue their usual care. GPs of the intervention group received a 4-h
educational training, built with previous qualitative data on CRC screening
focusing on doctor-patient communication with a follow-up of 7 months for both
groups. The primary outcome measure was the patients' participation rate in the
target population for each GP. Seventeen GPs (16 practices) in intervention group
and 28 GPs (19 practices) in control group participated. The patients'
participation rate in the intervention group were 36.7% vs. 24.5% in the control
group (P = 0.03). Doctor-patient communication should be developed and appear to
be one of the possible targets of improvement patients adherence and
participation rate in the target population for CRC mass screening.
PMID- 25851843
TI - Psychometric properties of the Musculoskeletal Function Assessment and the Short
Musculoskeletal Function Assessment: a systematic review.
AB - OBJECTIVES: To investigate the psychometric properties of the Musculoskeletal
Function Assessment (MFA) and Short Musculoskeletal Function Assessment (SMFA).
DATA SOURCES: A systematic search of the following databases was undertaken
concerning psychometric evidence of the MFA and SMFA: PubMed, Embase, Scopus and
Cinahl. References of retrieved articles were inspected for additional data.
REVIEW METHOD: Articles evaluating the validity, reliability or responsiveness of
the MFA or SMFA in patients with musculoskeletal disorders were included in this
systematic review. The methodological quality of included articles was critically
appraised and the psychometric data were extracted using standardized forms. An
established set of criteria were used to synthetize the evidence in order to
highlight the strengths and weaknesses of included questionnaires and the gaps in
the literature. RESULTS: Nine articles on MFA and 24 articles on SMFA met the
inclusion criteria. The SMFA fulfilled 75% of the psychometric criteria analyzed,
while the MFA fulfilled only 50%. MFA and SMFA have excellent content validity
and relative reliability (weighted average intraclass correlation coefficient ?
0.87), and are moderately to highly responsive (standardized response mean
between 0.65 and 1.13). Absolute reliability and clinically important difference
of both questionnaires need to be defined, while the construct validity of MFA
still needs to be established. CONCLUSION: MFA and SMFA are reliable and
responsive tools for monitoring the function of patients with various
musculoskeletal disorders. Still, research is needed to justify their usage in a
clinical setting.
PMID- 25851844
TI - Find-A-Code: how accurate is the international classification of diseases coding
system for aplastic anemia?
PMID- 25851845
TI - Fetal malposition: impact and management.
AB - Fetal malposition, either occiput posterior or transverse (OT), leads to greater
risk of cesarean delivery, prolonged labor, and increased perinatal morbidity.
Historically, there is a known association between epidural use and malposition
that was assumed to be due to the increased discomfort of laboring with a fetus
in the occiput posterior position. However, evidence now suggests that the
epidural itself may contribute to fetal malposition by impacting the probability
of internal rotation. Fetal malposition may be impacted by manual rotation.
Manual rotation has been associated with greater rates of delivering in the
occiput anterior position and lower rates of cesarean delivery.
PMID- 25851846
TI - Transition to Office-based Obstetric and Gynecologic Procedures: Safety,
Technical, and Financial Considerations.
AB - Office-based surgery is increasingly desired by patients and providers due to
ease of access, overall efficiency, reimbursement, and satisfaction. The adoption
of office-based surgery requires careful consideration of safety, efficacy, cost,
and feasibility within a providers practice. This article reviews the currently
available data regarding patient and provider satisfaction as well as practical
considerations of staffing, equipment, and supplies. To aid the practitioner,
issues of office-based anesthesia and safety with references to currently
available national guidelines and protocols are provided. Included is a brief
review of billing, coding, and reimbursement. Technical procedural aspects with
information and recommendations are summarized.
PMID- 25851847
TI - Management of twins: vaginal or cesarean delivery?
AB - Recent level I evidence from a single randomized-controlled trial has shown that
there is no difference in fetal or neonatal outcomes (composite of fetal/neonatal
death or serious neonatal morbidity) between planned cesarean delivery and
planned vaginal delivery for twins between 32 and 38 6/7 weeks. As long as the
presenting twin is vertex, vaginal delivery should be considered regardless of
the presentation of the second twin. To avoid unnecessary cesarean deliveries and
maternal morbidity, it is important to continue to train residents to perform
obstetrics maneuvers necessary for vaginal delivery of twins such as vaginal
breech extraction.
PMID- 25851848
TI - The Safe Prevention of the Primary Cesarean.
PMID- 25851849
TI - Promise and challenges of maternal health collaboratives.
AB - Quality-improvement collaboratives are just one of many tools used by health care
delivery systems to address quality and safety gaps. These initiatives usually
encompass specific aims, multidisciplinary teams, and information sharing. In the
recent years, there has been a significant increase in the number of maternal
health collaboratives with 31 states having a State Perinatal Quality
Collaborative. These programs have shown promise with significant gains in the
reduction of early elective deliveries. Further investments by stakeholders can
help contribute the resources needed to evaluate the effectiveness and cost
savings of maternal health collaboratives.
PMID- 25851850
TI - Induction of Labor and Cesarean: What is the True Relationship?
AB - It is a commonly held belief that labor induction increases the risk of cesarean
delivery; women who are induced are at higher risk of cesarean as compared with
those in spontaneous labor. This comparison group is inaccurate, however, as
women and providers cannot choose spontaneous labor as the alternative to labor
induction. With expectant management, spontaneous labor may occur, but as
gestation advances, pregnancy complications may occur, or women may progress
postterm requiring induction at a later gestation. Using the proper comparison
group, studies find that labor induction is actually associated with a small
decreased risk of cesarean delivery.
PMID- 25851851
TI - Second stage of labor.
AB - Current American College of Obstetricians and Gynecologists' definition of
prolonged second stage diagnoses 10% to 14% of nulliparous and 3% to 3.5% of
multiparous women as having a prolonged second stage. The progression of labor in
modern obstetrics may have deviated from the current labor norms established in
the 1950s, likely due to differences in obstetric population characteristics and
variation in clinical practice. Optimal management of the second stage in women
with and without epidural remains debatable. Although prolonged second stage is
associated with increased risk of maternal morbidity, conflicting data exist
regarding the duration of second stage and associated neonatal morbidity and
mortality.
PMID- 25851852
TI - The association of elevated trough serum vancomycin concentrations with obesity.
AB - BACKGROUND: Obese patients display differences in vancomycin drug disposition,
which may complicate attainment of appropriate serum vancomycin concentrations
(SVCs). This study was conducted to determine if obesity leads to trough SVCs
above the therapeutic range. METHODS: This retrospective cohort study sought to
determine the rate and predictors of high (i.e. >20 mg/L) serum trough levels
according to level of obesity. RESULTS: Increasing BMI predicted SVCs > 20 mg/L
after controlling for dose, age, and serum creatinine. Obese patients had
significantly higher mean trough SVCs compared to non-obese patients (16.5 mg/L
vs 12.1 mg/L, p = 0.004) and a significantly higher proportion of obese patients
had trough SVCs > 20 mg/L (18.9% vs 4.2%, p = 0.03). CONCLUSION: Increasing
obesity predicted higher probabilities of SVCs > 20 mg/L. Development of
alternative dosing and management strategies for vancomycin may be necessary to
account for pharmacokinetic changes associated with obesity.
PMID- 25851853
TI - Early measurement of urinary N-acetyl-beta-glucosaminidase helps predict severe
hyponatremia associated with cisplatin-containing chemotherapy.
AB - BACKGROUND: Although cisplatin is a widely used anticancer drug for treating
various types of cancer, its clinical application is limited by severe systemic
toxicities, such as nephropathy, hematologic toxicity, and gastrointestinal
toxicity. There are no reliable and validated biomarkers to predict adverse
events caused by cisplatin. METHODS: Sixty-six patients who underwent cisplatin
containing first-line chemotherapy between June 2010 and November 2013 were
retrospectively analyzed. Data on urinary N-acetyl-beta-glucosaminidase
activities measured 24-48 h after cisplatin infusion were retrieved, and adverse
events during the first course of chemotherapy were recorded according to the
Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Patient
characteristics were: male/female 60/6, median age 65 (range 36-78) years,
esophageal/gastric/other cancer 60/4/2, chemotherapy regimen docetaxel-cisplatin
fluorouracil/fluorouracil-cisplatin/S-1-cisplatin 54/8/4, cisplatin dose (mg/sm)
60/70/80 16/43/7. Grade 3/4 adverse events were leukopenia (40.9%), neutropenia
(54.4%), febrile neutropenia (37.9%), hyponatremia (28.8%), and acute kidney
injury (37.9%). Patients with 20 units/gram creatinine or higher urinary N-acetyl
beta-glucosaminidase developed statistically lower minimum serum sodium
concentration (median 126 vs. 134 mEq/L, p = 0.0053). There were no significant
correlations between urinary N-acetyl-beta-glucosaminidase and the development of
other severe adverse events. CONCLUSION: Early significant increase in urinary N
acetyl-beta-glucosaminidase predicts subsequent development of severe
hyponatremia after cisplatin-containing chemotherapy.
PMID- 25851854
TI - Emotional symptoms among adolescents: epidemiological analysis of individual-,
classroom- and school-level factors.
AB - BACKGROUND: Large proportions of schoolchildren suffer from emotional symptoms
and there are large variations across schools. It is unknown to what degree this
variation is due to composition of schoolchildren in each school or to contextual
factors. Objectives are to identify factors at individual, classroom and school
levels associated with emotional symptoms. METHOD: Data stem from the Danish
contribution to the international Health Behaviour in School-aged Children study
2010 including 4922 schoolchildren aged 11-15-years from a random sample of
schools and including data from school leaders. Emotional symptoms are defined as
daily presence of at least one of four symptoms: feeling low, irritable or bad
tempered, nervous and having difficulties falling asleep. Multilevel
multivariable logistic regression analyses are applied to identify and quantify
factors at individual, classroom and school level. RESULTS: Schoolchildren from
low (odds ratio (OR) 1.70, 95% CI: 1.33-2.17) and medium (OR 1.50, 95% CI: 1.22
1.85) occupational social class (OSC), girls (OR 1.32, 95% CI: 1.13-1.56) and
schoolchildren exposed to bullying (OR 3.82, 95% CI: 2.71-5.40), had increased
odds for emotional symptoms. A negative classroom climate was associated with
emotional symptoms (OR 1.29, 95% CI: 0.99-1.69) and so was being part of
classrooms with a high prevalence of bullying (OR 1.28, 95% CI: 1.0-1.60).
CONCLUSION: Female sex, low OSC, single parent family, exposure to bullying and a
high prevalence of bullying within a class are all associated with emotional
symptoms. Most variation across schools is explained by individual-level factors
but psychosocial aspects of the classroom environment also play a role.
PMID- 25851856
TI - Targeting backup DNA repair in cancer.
AB - New research shows that DNA polymerase theta is a key player in PARP-mediated DNA
damage repair and essential for the survival of cancer cells where homologous
recombination is compromised. Poltheta could be a biomarker for PARP-inhibitor
response, and is a potential therapeutic target for overcoming resistance to
these drugs.
PMID- 25851857
TI - Philanthropies team up to fund young scientists.
AB - The Howard Hughes Medical Institute, the Bill & Melinda Gates Foundation, and the
Simons Foundation announced an initiative to support talented, early-career
scientists working in biology and biomedical research. They plan to invest $148
million in the program over the next 5 years.
PMID- 25851858
TI - Breast cancer susceptibility genes pile up.
AB - A large genome-wide association analysis has revealed 15 more SNPs associated
with breast cancer, which could provide additional genetic markers for risk
analysis.
PMID- 25851859
TI - Dinutuximab approved for high-risk neuroblastoma.
AB - The FDA approved the use of dinutuximab, in combination with three other agents,
for high-risk neuroblastoma, offering patients the first major new treatment in
more than a decade.
PMID- 25851860
TI - Accurate evaluation of relationships among serum lipoprotein lipase mass,
visceral fat and retinal nerve fiber layer thickness.
PMID- 25851861
TI - Accurate evaluation of relationships among serum lipoprotein lipase mass,
visceral fat, and retinal nerve fiber layer thickness.
PMID- 25851862
TI - Vascular endothelial growth factor plasma levels before and after treatment of
retinopathy of prematurity with ranibizumab.
AB - PURPOSE: To evaluate vascular endothelial growth factor (VEGF) plasma levels
before and after intravitreal injection of ranibizumab in patients with
retinopathy of prematurity (ROP). METHODS: Case series study. Eleven infants with
type 1 pre-threshold ROP were treated with intravitreal ranibizumab 0.5 mg. Blood
samples were collected before intravitreal injection of ranibizumab and 1 day, 1
week, 2 weeks, and 4 weeks after injection. Concentration of plasma VEGF was
measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: The mean +/-
standard deviation of plasma VEGF concentration of the available samples before
and 1 day, 1 week, 2 weeks, and 4 weeks after a total of 0.5 mg ranibizumab
injection were 46.07 +/- 9.40 pg/ml (n = 11), 10.59 +/- 7.32 pg/ml (n = 5), 45.76
+/- 6.75 pg/ml (n = 5), 62.44 +/- 15.51 pg/ml (n = 5), and 56.82 +/- 12.78 pg/ml
(n = 4) respectively. A significant reduction was found in the plasma VEGF levels
1 day after intravitreal injection of ranibizumab (P = 0.002). No significant
differences were found between before and 1 week, 2 weeks, and 4 weeks after the
injection. CONCLUSIONS: Intravitreal ranibizumab reduced plasma VEGF levels 1 day
after injection in infants with ROP. This effect disappeared 1 week after the
injection. Intravitreal ranibizumab did not induce prolonged systemic VEGF
suppression.
PMID- 25851863
TI - Comment on: Park SW, Byon IS, Kim HY, Lee JE, Oum BS (2015) Analysis of the
ganglion cell layer and photoreceptor layer using optical coherence tomography
after idiopathic epiretinal membrane surgery. Graefes Arch Clin Exp Ophthalmol
253:207-14.
PMID- 25851864
TI - Erratum to: Effect of gravity in long-term vitreous tamponade: in vivo
investigation using perfluorocarbon liquids and semi-fluorinated alkanes.
PMID- 25851865
TI - Maternal and neonatal outcomes after implementation of a hospital policy to limit
low-risk planned caesarean deliveries before 39 weeks of gestation: an
interrupted time-series analysis.
AB - OBJECTIVE: To evaluate the extent to which implementing a hospital policy to
limit planned caesarean deliveries before 39 weeks of gestation improved neonatal
health, maternal health, and healthcare costs. DESIGN: Retrospective cohort
study. SETTING: British Columbia Women's Hospital, Vancouver, Canada, in the
period 2005-2012. POPULATION: Women with a low-risk planned repeat caesarean
delivery. METHODS: An interrupted time series design was used to evaluate the
policy to limit planned caesarean deliveries before 39 weeks of gestation,
introduced on 1 April 2008. MAIN OUTCOME MEASURES: Composite adverse neonatal
health outcome (respiratory morbidity, 5-minute Apgar score of <7, neonatal
intensive care unit admission, mortality), postpartum haemorrhage, obstetrical
wound infection, out-of-hour deliveries, length of stay, and healthcare costs.
RESULTS: Between 2005 and 2008, 60% (1204/2021) of low-risk planned caesarean
deliveries were performed before 39 weeks of gestation. After the introduction of
the policy, the proportion of planned caesareans dropped by 20 percentage points
(adjusted risk difference of 20 fewer cases per 100 deliveries; 95% CI -25.8,
14.3) to 41% (1033/2518). The policy had no detectable impact on adverse neonatal
outcomes (2.2 excess cases per 100; 95% CI -0.4, 4.8), maternal complications, or
healthcare costs, but increased the risk of out-of-hours delivery from 16.2 to
21.1% (adjusted risk difference 6.3 per 100; 95% CI 1.6, 10.9). CONCLUSIONS: We
found little evidence that a hospital policy to limit planned caesareans before
39 weeks of gestation reduced adverse neonatal outcomes. Hospital administrators
intending to introduce such policies should anticipate, and plan for, modest
increases in out-of-hours and emergency-timing.
PMID- 25851866
TI - Review insights into the interactions of amino acids and peptides with inorganic
materials using single molecule force spectroscopy.
AB - Understanding the interactions between proteins and inorganic surfaces is
important for the development of new biomaterials and implants as they interface
with the immune response by proteins. In addition, the adsorption of proteins to
inorganic surfaces leads to the formation of a conditioning layer that
facilitates bacterial attachments and biofilm formation. As biofilm provides
bacterial resistance to antibiotics, biofilm formation is an undesirable process
that could be prevented by resisting protein interactions with the substrate.
Moreover, the interaction between proteins and inorganic materials is the basis
for the formation of composite materials in nature. Understanding the underlying
forces that governs these interactions would lead to the design of new and unique
composite materials in vitro. This review focuses on the insights gained using
single-molecule force spectroscopy by AFM on these interactions. This tool
provides molecular information, at the single molecule level, on the interaction
between a molecule on the AFM tip and a substrate.
PMID- 25851889
TI - Neuromuscular ultrasound of cranial nerves.
AB - Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound
(NMUS) which may provide additional value in the assessment of cranial nerves in
different neuromuscular disorders. Whilst NMUS of peripheral nerves has been
studied, NMUS of cranial nerves is considered in its initial stage of research,
thus, there is a need to summarize the research results achieved to date.
Detailed scanning protocols, which assist in mastery of the techniques, are
briefly mentioned in the few reference textbooks available in the field. This
review article focuses on ultrasound scanning techniques of the 4 accessible
cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant
literatures and potential future applications are discussed.
PMID- 25851890
TI - Chasing tics in the human brain: development of open, scheduled and closed loop
responsive approaches to deep brain stimulation for tourette syndrome.
AB - Tourette syndrome is a childhood-onset disorder characterized by a combination of
motor and vocal tics, often associated with psychiatric comorbidities including
attention deficit and hyperactivity disorder and obsessive-compulsive disorder.
Despite an onset early in life, half of patients may present symptoms in
adulthood, with variable degrees of severity. In select cases, the syndrome may
lead to significant physical and social impairment, and a worrisome risk for self
injury. Evolving research has provided evidence supporting the idea that the
pathophysiology of Tourette syndrome is directly related to a disrupted circuit
involving the cortex and subcortical structures, including the basal ganglia,
nucleus accumbens, and the amygdala. There has also been a notion that a
dysfunctional group of neurons in the putamen contributes to an abnormal
facilitation of competing motor responses in basal ganglia structures ultimately
underpinning the generation of tics. Surgical therapies for Tourette syndrome
have been reserved for a small group of patients not responding to behavioral and
pharmacological therapies, and these therapies have been directed at modulating
the underlying pathophysiology. Lesion therapy as well as deep brain stimulation
has been observed to suppress tics in at least some of these cases. In this
article, we will review the clinical aspects of Tourette syndrome, as well as the
evolution of surgical approaches and we will discuss the evidence and clinical
responses to deep brain stimulation in various brain targets. We will also
discuss ongoing research and future directions as well as approaches for open,
scheduled and closed loop feedback-driven electrical stimulation for the
treatment of Tourette syndrome.
PMID- 25851891
TI - A consensus in Korea regarding a protocol to reduce preanalytical sources of
variability in the measurement of the cerebrospinal fluid biomarkers of
Alzheimer's disease.
AB - Cerebrospinal fluid (CSF) can provide vital informative about pathological
processes occurring in the brain. In particular, the CSF concentrations of
Abeta42, tTau, and pTau181 are useful for the early diagnosis of Alzheimer's
disease (AD). However, many studies have demonstrated that confounding factors
related to the preanalytical processing of CSF can seriously influence
measurements of these AD biomarkers. It is therefore important to develop a
standardized protocol for the acquisition and handling of CSF, particularly with
regard to the types of tube used for collection and storage, the proper aliquot
volume, blood contamination, and the number of tube transfers and freeze-thaw
cycles, because these aspects of the procedure have been shown to affect AD
biomarker measurements. A survey of the impact of several individual
preanalytical procedures on the measurement of AD biomarkers in CSF was conducted
for this review article, and the implications of the differences among them are
discussed. Furthermore, following a review of the procedures used in Korean and
international biomarker laboratories, a consensus was reached among a cooperative
Korean multicenter research group regarding a standardized protocol for the
analysis of AD biomarkers in CSF. All efforts were made to be stringent regarding
the controversial issues associated with this protocol, thus minimizing the
confounding influence of various factors on current investigations using
established AD biomarkers and on future studies using novel biomarkers of AD and
other neurodegenerative disorders.
PMID- 25851892
TI - Feasibility of using a mobile application for the monitoring and management of
stroke-associated risk factors.
AB - BACKGROUND AND PURPOSE: Recent advances in information technology have created
opportunities for advances in the management of stroke. The objective of this
study was to test the feasibility of using a smartphone software application
(app) for the management of vascular risk factors in patients with stroke.
METHODS: This prospective clinical trial developed a smartphone app, the 'Korea
University Health Monitoring System for Stroke: KUHMS2,' for use by patients with
stroke. During a 6-month follow-up period, its feasibility was assessed by
measuring the changes in their vascular risk-factor profiles and the number of
days per patient with data registration into the app. The effect of the app on
the achievement rate of risk-factor targets was assessed by classifying subjects
into compliant and noncompliant groups. RESULTS: At the end of the trial, data on
48 patients were analyzed. The number of days on which data were registered into
the app was 60.42+/-50.17 (mean+/-standard deviation). Among predefined vascular
risk factors, the target achievement rate for blood pressure and glycated
hemoglobin (Hb(A1c)) improved significantly from baseline to the final
measurement. The serial changes in achievement rates for risk-factor targets did
not differ between the compliant and noncompliant groups. CONCLUSIONS: Many
challenges must be overcome before mobile apps can be used for patients with
stroke. Nevertheless, the app tested in this study induced a shift in the risk
profiles in a favorable direction among the included stroke patients.
PMID- 25851893
TI - Effect of carotid artery stenting on cognitive function in patients with carotid
artery stenosis: a prospective, 3-month-follow-up study.
AB - BACKGROUND AND PURPOSE: Carotid artery stenting (CAS) is emerging as an
alternative to carotid endarterectomy for the treatment of carotid artery
stenosis (CS), but the effect of CAS on the cognitive function of patients with
severe CS has not been fully investigated. The aim of this study was to use
comprehensive neuropsychological tests to determine the effect of CAS on
cognitive function from baseline to 3 months postprocedure in patients with
severe CS. METHODS: Thirty-one patients due to undergo CAS due to high-grade CS
(>=70%) and 11 control subjects who were diagnosed with CS, but who did not
undergo CAS, and who visited the clinic or emergency room between February 2009
and February 2012 were recruited consecutively at baseline (i.e., pre-CAS).
Follow-up neuropsychological evaluations after 3 months were completed by 23 of
the 31 patients who underwent CAS, and by 10 of the 11 control subjects. The
primary cognitive outcome was assessed using a neuropsychological test containing
subcategories designed to test general cognitive function, attention,
visuospatial function, language and related functions, memory, and frontal
lobe/executive function. RESULTS: Of the 23 patients undergoing CAS who completed
the 3-month follow-up tests, 12 had asymptomatic CS. During the 3-month follow-up
period, the patients who underwent CAS and those with asymptomatic CS achieved
similar results to the control group on all cognitive tests. However, symptomatic
CS patients (n=11) who underwent CAS exhibited improvements in visuospatial
function (p=0.046) and total Seoul Neuropsychological Screening Battery-Dementia
Version scores (p=0.010) in comparison with both the asymptomatic CS patients and
the control group. CONCLUSIONS: The findings of this study suggest that CAS has a
positive effect on cognitive function in patients with symptomatic CS over a 3
month follow-up period. A long-term, multicenter, prospective case-control study
would be helpful to predict quality of life and prognoses for patients undergoing
CAS.
PMID- 25851894
TI - The Persian Version of a Participation Scale: Is It Valid and Reliable Enough for
Use among Iranian Patients with Multiple Sclerosis?
AB - BACKGROUND AND PURPOSE: The aim of this study was to determine the face and
criterion validity, stability reliability, and internal consistency of the
Persian version of the Impact on Participation and Autonomy (IPA-p) scale among
Iranian people with multiple sclerosis (MS). METHODS: Trained experts interviewed
364 MS patients and their relatives to assess the criterion validity, stability
reliability, and internal consistency of the IPA-p scale. Ten specialists from
different disciplines were also recruited to assess its face validity. A consent
form was completed by the patients and their relatives. Internal consistency
reliability was measured using Cronbach's alpha and stability reliability was
assessed using interclass correlation coefficients (ICCs). The test-retest method
was used to detect the reliability of the questioner. The study subjects
completed the IPA-p scale on two occasions separated by an interval of 30-45
days. Study checklists were also used to assess the face validity, stability
reliability, and internal consistency of the IPA-p scale. RESULTS: About 50% of
the respondents reported their perceived overall participation to be "good" or
"very good" and 60% of the specialists rated the ability of the IPA-p scale to
measure what it was designed for as "excellent." Spearman correlation
coefficients were >0.8 for all but one IPA-p domain. Cronbach's alpha between the
mean IPA-p scale scores achieved on two separate occasions ranged from 0.858 to
0.913. The highest and lowest internal consistencies belonged to the "social
relationships" and "education and learning" domains, respectively. The test
retest ICCs for the nine domains were between 0.789 and 0.919, and all were
significant at p<0.001. CONCLUSIONS: The IPA-p questionnaire can be considered a
valid and reliable instrument for assessing self-reported participation among
Iranian MS patients.
PMID- 25851895
TI - Granulocyte colony-stimulating factor for amyotrophic lateral sclerosis: a
randomized, double-blind, placebo-controlled study of Iranian patients.
AB - BACKGROUND AND PURPOSE: The aim of this study was to determine the efficacy and
tolerability of granulocyte colony-stimulating factor (G-CSF) in subjects with
amyotrophic lateral sclerosis (ALS). METHODS: Forty subjects with ALS were
randomly assigned to two groups, which received either subcutaneous G-CSF (5
MUg/kg/q12h) or placebo for 5 days. The subjects were then followed up for 3
months using the ALS Functional Rating Scale-Revised (ALSFRS-R), manual muscle
testing, ALS Assessment Questionnaire-40, and nerve conduction studies.
CD34+/CD133+ cell count and monocyte chemoattractant protein-1 (MCP-1) levels
were evaluated at baseline. RESULTS: The rate of disease progression did not
differ significantly between the two groups. The reduction in ALSFRS-R scores was
greater in female subjects in the G-CSF group than in their counterparts in the
placebo group. There was a trend toward a positive correlation between baseline
CSF MCP-1 levels and the change in ALSFRS-R scores in both groups (Spearman's
rho=0.370, p=0.070). CONCLUSIONS: With the protocol implemented in this study, G
CSF is not a promising option for the treatment of ALS. Furthermore, it may
accelerate disease progression in females.
PMID- 25851896
TI - Preclinical assessment of the anticancer drug response of plexiform neurofibroma
tissue using primary cultures.
AB - BACKGROUND AND PURPOSE: Individualized drug testing for tumors using a strategy
analogous to antibiotic tests for infectious diseases would be highly desirable
for personalized and individualized cancer care. METHODS: Primary cultures
containing tumor and nontumor stromal cells were utilized in a novel strategy to
test drug responses with respect to both efficacy and specificity. The strategy
tested in this pilot study was implemented using four primary cultures derived
from plexiform neurofibromas. Responses to two cytotoxic drugs (nilotinib and
imatinib) were measured by following dose-dependent changes in the proportions of
tumor and nontumor cells, determined by staining them with cell-type-specific
antibodies. The viability of the cultured cells and the cytotoxic effect of the
drugs were also measured using proliferation and cytotoxicity assays. RESULTS:
The total number of cells decreased after the drug treatment, in accordance with
the observed reduction in proliferation and increased cytotoxic effect upon
incubation with the two anticancer drugs. The proportions of Schwann cells and
fibroblasts changed dose-dependently, although the patterns of change varied
between the tumor samples (from different sources) and between the two drugs. The
highly variable in vitro drug responses probably reflect the large variations in
the responses of tumors to therapies between individual patients in vivo.
CONCLUSIONS: These preliminary results suggest that the concept of assessing in
vitro drug responses using primary cultures is feasible, but demands the
extensive further development of an application for preclinical drug selection
and drug discovery.
PMID- 25851897
TI - The usefulness of proximal radial motor conduction in acute compressive radial
neuropathy.
AB - BACKGROUND AND PURPOSE: The objective of this study was to determine diagnostic
and prognostic values of proximal radial motor conduction in acute compressive
radial neuropathy. METHODS: Thirty-nine consecutive cases of acute compressive
radial neuropathy with radial conduction studies-including stimulation at Erb's
point-performed within 14 days from clinical onset were reviewed. The radial
conduction data of 39 control subjects were used as reference data. RESULTS:
Thirty-one men and eight women (age, 45.2+/-12.7 years, mean+/-SD) were enrolled.
All 33 patients in whom clinical follow-up data were available experienced
complete recovery, with a recovery time of 46.8+/-34.3 days. Partial conduction
block was found frequently (17 patients) on radial conduction studies. The
decrease in the compound muscle action potential area between the arm and Erb's
point was an independent predictor for recovery time. CONCLUSIONS: Proximal
radial motor conduction appears to be a useful method for the early detection and
prediction of prognosis of acute compressive radial neuropathy.
PMID- 25851898
TI - PEX7 Mutations Cause Congenital Cataract Retinopathy and Late-Onset Ataxia and
Cognitive Impairment: Report of Two Siblings and Review of the Literature.
PMID- 25851899
TI - Utility of oblique coronal images in elderly and cognitively impaired patients.
PMID- 25851900
TI - Reconsidering the detection of tolerance to individualize immunosuppression
minimization and to improve long-term kidney graft outcomes.
AB - In kidney transplantation, minimizing the side effects of the immunosuppressive
regimen and inducing tolerance to allograft are the two main objectives to
improve outcome. At present, these objectives are far from being achieved and
remain elusive for the majority of transplant recipients. Rejection rate and
mortality on the long term are still unacceptable. There is thus a pressing need
to improve this situation. Therefore, some spontaneously tolerant kidney
recipients are described in clinics, and recent advances in immunological and
molecular techniques have led to a resurgence of interest in studying those rare
transplanted recipients through coordinated efforts from international consortia.
Indeed, they offer, on the one hand, the possibility to develop specific
biomarkers indicative of this state that would constitute a major advantage in
the care of the patients allowing personalized minimization of drugs, so reducing
related costs and side effects. On the other hand, they represent a unique model
of study to understand the mechanisms of regulation implicated in this state that
may help the development of inducing therapies. Recent efforts, concentrated on
noninvasive analyses of peripheral blood, identified a predominance of several B
cell subsets, some of which harbouring regulatory functions, and related marker
genes. These findings, validated in independent multicentric cohorts, led
credence to an unsuspected role for the B-cell compartment in tolerance to kidney
allograft. The identification of patients, harbouring these markers, among
immunosuppressed recipients with stable graft function and the existence of drugs
with selective effect on B cell pave the way for the possibility to improve long
term graft outcomes. Therefore, before routine application, these findings need
to be confirmed in large prospective studies in the context of planned reduced
immunosuppression.
PMID- 25851901
TI - Methylosome Protein 50 and PKCdelta/p38delta Protein Signaling Control
Keratinocyte Proliferation via Opposing Effects on p21Cip1 Gene Expression.
AB - Protein arginine methyltransferase 5 (PRMT5) is a key epigenetic regulator that
symmetrically dimethylates arginine residues on histones H3 and H4 to silence
gene expression. PRMT5 is frequently observed in a complex with the cofactor
methylosome protein 50 (MEP50), which is required for PRMT5 activity.
PKCdelta/p38delta signaling, a key controller of keratinocyte proliferation and
differentiation, increases p21(Cip1) expression to suppress keratinocyte
proliferation. We now show that MEP50 enhances keratinocyte proliferation and
survival via mechanisms that include silencing of p21(Cip1) expression. This is
associated with enhanced PRMT5-MEP50 interaction at the p21(Cip1) promoter and
enhanced arginine dimethylation of the promoter-associated histones H3 and H4. It
is also associated with a MEP50-dependent reduction in the level of p53, a key
controller of p21(Cip1) gene expression. We confirm an important biological role
for MEP50 and PRMT5 in regulating keratinocyte proliferation using a stratified
epidermal equivalent model that mimics in vivo epidermal keratinocyte
differentiation. In this model, PRMT5 or MEP50 knockdown results in reduced
keratinocyte proliferation. We further show that PKCdelta/p38delta signaling
suppresses MEP50 expression, leading to reduced H3/H4 arginine dimethylation at
the p21(Cip1) promoter, and that this is associated with enhanced p21(Cip1)
expression and reduced cell proliferation. These findings describe an opposing
action between PKCdelta/p38delta MAPK signaling and PRMT5/MEP50 epigenetic
silencing mechanisms in regulating cell proliferation.
PMID- 25851902
TI - Thiobenzothiazole-modified Hydrocortisones Display Anti-inflammatory Activity
with Reduced Impact on Islet beta-Cell Function.
AB - Glucocorticoids signal through the glucocorticoid receptor (GR) and are
administered clinically for a variety of situations, including inflammatory
disorders, specific cancers, rheumatoid arthritis, and organ/tissue
transplantation. However, glucocorticoid therapy is also associated with
additional complications, including steroid-induced diabetes. We hypothesized
that modification of the steroid backbone is one strategy to enhance the
therapeutic potential of GR activation. Toward this goal, two commercially
unavailable, thiobenzothiazole-containing derivatives of hydrocortisone (termed
MS4 and MS6) were examined using 832/13 rat insulinoma cells as well as rodent
and human islets. We found that MS4 had transrepression properties but lacked
transactivation ability, whereas MS6 retained both transactivation and
transrepression activities. In addition, MS4 and MS6 both displayed anti
inflammatory activity. Furthermore, MS4 displayed reduced impact on islet beta
cell function in both rodent and human islets. Similar to dexamethasone, MS6
promoted adipocyte development in vitro, whereas MS4 did not. Moreover, neither
MS4 nor MS6 activated the Pck1 (Pepck) gene in primary rat hepatocytes. We
conclude that modification of the functional groups attached to the D-ring of the
hydrocortisone steroid molecule produces compounds with altered structure
function GR agonist activity with decreased impact on insulin secretion and
reduced adipogenic potential but with preservation of anti-inflammatory activity.
PMID- 25851903
TI - Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary
Gland Development and Function during Lactation.
AB - The zinc transporter ZnT2 (SLC30A2) imports zinc into vesicles in secreting
mammary epithelial cells (MECs) and is critical for zinc efflux into milk during
lactation. Recent studies show that ZnT2 also imports zinc into mitochondria and
is expressed in the non-lactating mammary gland and non-secreting MECs,
highlighting the importance of ZnT2 in general mammary gland biology. In this
study we used nulliparous and lactating ZnT2-null mice and characterized the
consequences on mammary gland development, function during lactation, and milk
composition. We found that ZnT2 was primarily expressed in MECs and to a limited
extent in macrophages in the nulliparous mammary gland and loss of ZnT2 impaired
mammary expansion during development. Secondly, we found that lactating ZnT2-null
mice had substantial defects in mammary gland architecture and MEC function
during secretion, including fewer, condensed and disorganized alveoli, impaired
Stat5 activation, and unpolarized MECs. Loss of ZnT2 led to reduced milk volume
and milk containing less protein, fat, and lactose compared with wild-type
littermates, implicating ZnT2 in the regulation of mammary differentiation and
optimal milk production during lactation. Together, these results demonstrate
that ZnT2-mediated zinc transport is critical for mammary gland function,
suggesting that defects in ZnT2 not only reduce milk zinc concentration but may
compromise breast health and increase the risk for lactation insufficiency in
lactating women.
PMID- 25851904
TI - Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing
Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8.
AB - Ganglioside GD2 is highly expressed on neuroectodermal tumors and an attractive
therapeutic target for antibodies that have already shown some clinical efficacy.
To further improve the current antibodies, which have modest affinity, we sought
to improve affinity by using a combined method of random mutagenesis and in
silico assisted design to affinity-mature the anti-GD2 monoclonal antibody hu3F8.
Using yeast display, mutants in the Fv with enhanced binding over the parental
clone were FACS-sorted and cloned. In silico modeling identified the minimal key
interacting residues involved in the important charged interactions with the
sialic acid groups of GD2. Two mutations, D32H (L-CDR1) and E1K (L-FR1) altered
the electrostatic surface potential of the antigen binding site, allowing for an
increase in positive charge to enhance the interaction with the negatively
charged GD2-pentasaccharide headgroup. Purified scFv and IgG mutant forms were
then tested for antigen specificity by ELISA, for tissue specificity by
immunohistochemistry, for affinity by BIACORE, for antibody-dependent cell
mediated cytotoxicity (ADCC) and complement-mediated cytotoxicity in vitro, and
for anti-tumor efficacy in xenografted humanized mice. The nearly 7-fold
improvement in affinity of hu3F8 with a single D32H (L-CDR1) mutation translated
into a ~12-fold improvement in NK92MI-transfected CD16-mediated ADCC, a 6-fold
improvement in CD32-mediated ADCC, and a 2.5-fold improvement in complement
mediated cytotoxicity while maintaining restricted normal tissue cross-reactivity
and achieving substantial improvement in tumor ablation in vivo. Despite
increasing GD2 affinity, the double mutation D32H (L-CDR1) and E1K (L-FR1) did
not further improve anti-tumor efficacy.
PMID- 25851905
TI - Organization of Subunits in the Membrane Domain of the Bovine F-ATPase Revealed
by Covalent Cross-linking.
AB - The F-ATPase in bovine mitochondria is a membrane-bound complex of about 30
subunits of 18 different kinds. Currently, ~85% of its structure is known. The
enzyme has a membrane extrinsic catalytic domain, and a membrane intrinsic domain
where the turning of the enzyme's rotor is generated from the transmembrane
proton-motive force. The domains are linked by central and peripheral stalks. The
central stalk and a hydrophobic ring of c-subunits in the membrane domain
constitute the enzyme's rotor. The external surface of the catalytic domain and
membrane subunit a are linked by the peripheral stalk, holding them static
relative to the rotor. The membrane domain contains six additional subunits named
ATP8, e, f, g, DAPIT (diabetes-associated protein in insulin-sensitive tissues),
and 6.8PL (6.8-kDa proteolipid), each with a single predicted transmembrane alpha
helix, but their orientation and topography are unknown. Mutations in ATP8
uncouple the enzyme and interfere with its assembly, but its roles and the roles
of the other five subunits are largely unknown. We have reacted accessible amino
groups in the enzyme with bifunctional cross-linking agents and identified the
linked residues. Cross-links involving the supernumerary subunits, where the
structures are not known, show that the C terminus of ATP8 extends ~70 A from the
membrane into the peripheral stalk and that the N termini of the other
supernumerary subunits are on the same side of the membrane, probably in the
mitochondrial matrix. These experiments contribute significantly toward building
up a complete structural picture of the F-ATPase.
PMID- 25851907
TI - [Gender inequality in the authorship of medical articles: Analysis of Medicina
Clinica, 1999 and 2014].
PMID- 25851906
TI - Kruppel-like Factor 4 Promotes Esophageal Squamous Cell Carcinoma Differentiation
by Up-regulating Keratin 13 Expression.
AB - Squamous cell differentiation requires the coordinated activation and repression
of genes specific to the differentiation process; disruption of this program
accompanies malignant transformation of epithelium. The exploration of genes that
control epidermal proliferation and terminal differentiation is vital to better
understand esophageal carcinogenesis. KLF4 is a member of the KLF family of
transcription factors and is involved in both cellular proliferation and
differentiation. This study using immunohistochemistry analysis of KLF4 in
clinical specimens of esophageal squamous cell carcinoma (ESCC) demonstrated that
decreased KLF4 was substantially associated with poor differentiation. Moreover,
we determined that both KLF4 and KRT13 levels were undoubtedly augmented upon
sodium butyrate-induced ESCC differentiation and G1 phase arrest. Conversely,
silencing of KLF4 and KRT13 abrogated the inhibition of G1-S transition induced
by sodium butyrate. Molecular investigation demonstrated that KLF4
transcriptionally regulated KRT13 and the expression of the two molecules
appreciably correlated in ESCC tissues and cell lines. Collectively, these
results suggest that KLF4 transcriptionally regulates KRT13 and is invovled in
ESCC cell differentiation.
PMID- 25851908
TI - [First case of bacteremia by Sphingomonas anadarae in an patient with cancer].
PMID- 25851909
TI - [Autoimmune endocrinopathies induced by immunomodulating antibodies in the
treatment of cancer].
PMID- 25851910
TI - [Follicular mycosis fungoides, a rare and aggressive variant].
PMID- 25851911
TI - [Symmetrical polyarthritis in a patient with multicentric reticulohistiocytosis].
PMID- 25851912
TI - [Vaccination of patients with non-Hodgkin lymphoma under rituximab or other
immunosuppressive drugs].
PMID- 25851913
TI - [Central neurogenic hyperventilation in a patient with post-vaccination acute
disseminated encephalomyelitis].
PMID- 25851914
TI - [Ocular thelaziosis, an emergent zoonosis in Spain].
PMID- 25851915
TI - [The current role of autopsy in current clinical practice].
PMID- 25851916
TI - A hypothesis for reactivation of pulmonary tuberculosis: How thoracic wall shape
affects the epidemiology of tuberculosis.
AB - This study was aimed at determining the cause for the high incidence of
tuberculosis (TB) reactivation occurring in males with a low body mass index
(BMI). Current thinking about pulmonary TB describes infection in the lung apex
resulting in cavitation after reactivation. A different hypothesis is put forward
for TB infection, suggesting that this occurs in subclinical apical cavities
caused by increased pleural stress due to a low BMI body habitus. A finite
element analysis (FEA) model of a lung was constructed including indentations for
the first rib guided by paramedian sagittal CT reconstructions, and simulations
were conducted with varying antero-posterior (AP) diameters to mimic chests with
a different thoracic index (ratio of AP to the transverse chest diameters). A
Pubmed search was conducted about gender and thoracic index, and the effects of
BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung
apex in low BMI chests, and a four-fold increase with a low thoracic index, r(2)
= 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean
thoracic index was statistically significantly lower in males, P = 0.001, and
increased with age in both genders. This article is the first to suggest a
possible mechanism linking pulmonary TB reactivation to low BMI due to the
flattened thoracic wall shape of young male adults. The low thoracic index in
young males may promote TB reactivation due to tissue destruction in the lung
apex from high pleural stress levels.
PMID- 25851917
TI - The experiences of emergency nurses in providing end-of-life care to patients in
the emergency department.
AB - BACKGROUND: Managing death in the emergency department is a challenge. Emergency
nurses are expected to provide care to numerous patient groups in an often fast
paced, life-saving environment. The purpose of this study was to describe the
experiences of emergency nurses in providing end-of-life care, which is the care
delivered to a patient during the time directly preceding death. METHOD: Data
were collected from 25 emergency nurses during three focus group interviews. The
interviews were transcribed and analysed using the qualitative techniques of
grounded theory. RESULTS: Ten categories emerged from the data that described a
social process for managing death in the emergency department. The categories
were linked via the core category labelled 'dying in the emergency department is
not ideal', which described how the emergency department was an inappropriate
place for death to occur. To help manage the influence of the environment on end
of-life care, nurses reported strategies that included moving dying patients out
of the emergency department and providing the best care that they could.
CONCLUSION: The results of this study highlight nurses' belief that the emergency
department was not an appropriate place for death to occur. Despite being
frequently exposed to death and dying, the actions and attitudes of emergency
nurses implied the need or desire to avoid death in the emergency department.
PMID- 25851918
TI - Human performance on random ratio and random interval schedules, performance
awareness and verbal instructions.
AB - Humans responded on multiple random-ratio (RR) random-interval (RI) schedules,
and their verbalized performance awareness (PA; i.e., their ability to accurately
describe what they did) was measured in three experiments. In Experiment 1,
instructions informed participants that to earn points, either sometimes rapid
responding and sometimes slow responding would work best (accurate instructions);
rapid responding would work best (go fast instructions); spaced responding would
work best (go slow instructions); or no advice was provided (minimal
instructions). In Experiments 2 and 3, participants received either accurate or
minimal instructions and were subject to extinction after a multiple RR-RI
schedule. In all experiments, both performance awareness, and receiving accurate
instructions, were related to schedule-sensitive responding, but were unrelated
to one another - participants receiving accurate-rate instructions were not more
likely to show performance awareness than those exposed to minimal instructions.
Both higher performance awareness and exposure to accurate instructions predicted
faster extinction in Experiment 2 but not in Experiment 3. The current results
suggest that performance awareness rather than contingency awareness is more
strongly related to humans displaying schedule-typical behavior and that this is
not strongly related to any explicit verbal instructions that are given.
PMID- 25851919
TI - Strain-dependent variations in visceral sensitivity: relationship to stress,
anxiety and spinal glutamate transporter expression.
AB - Responses to painful stimuli differ between populations, ethnic groups, sexes and
even among individuals of a family. However, data regarding visceral pain are
still lacking. Thus, we investigated differences in visceral nociception across
inbred and outbred mouse strains using colorectal distension. Anxiety and
depression-like behaviour were assessed using the open field and forced swim test
as well as the corticosterone stress response. Possible mechanistic targets
[excitatory amino acid transporter (EAAT-1), brain-derived neurotrophic factor
(BDNF) and 5HT1A receptor] were also assessed using quantitative real-time
polymerase chain reaction. Adult, male, inbred and outbred mouse strains were
used in all assays (inbred strains; CBA/J Hsd, C3H/HeNHsd, BALB/c OlaHsd, C57
BL/6JOlaHsd, DBA/2J RccHsd, CAST/EiJ, SM/J, A/J OlaHsd, 129P2/OlaHsd, FVB/NHan
Hsd and outbred strains: Swiss Webster, CD-1). mRNA expression levels of EAAT-1,
BDNF and 5HT1A receptor (HTR1A) were quantified in the lumbosacral spinal cord,
amygdala and hippocampus. A significant effect of strain was found in visceral
sensitivity, anxiety and depressive-like behaviours. Strain differences were also
seen in both baseline and stress-induced corticosterone levels. CBA/J mice
consistently exhibited heightened visceral sensitivity, anxiety behaviour and
depression-like behaviour which were associated with decreased spinal EAAT-1 and
hippocampal BDNF and HTR1A. Our results show the CBA/J mouse strain as a novel
mouse model to unravel the complex mechanisms of brain-gut axis disorders such as
irritable bowel syndrome, in particular the underlying mechanisms of visceral
hypersensitivity, for which there is great need. Furthermore, this study
highlights the importance of genotype and the consequences for future development
of transgenic strains in pain research.
PMID- 25851920
TI - Detection of Dirofilaria immitis and other arthropod-borne filarioids by an HRM
real-time qPCR, blood-concentrating techniques and a serological assay in dogs
from Costa Rica.
AB - BACKGROUND: Canine filarioids are important nematodes transmitted to dogs by
arthropods. Diagnosis of canine filariosis is accomplished by the microscopic
identification of microfilariae, serology or PCR for filarial-DNA. The aim of
this study was to evaluate a molecular assay for the detection of canine filariae
in dog blood, to compare its performance to other diagnostic techniques, and to
determine the relationship between microfilarial concentration and infection with
other vector-borne pathogens. METHODS: Blood samples from 146 dogs from Costa
Rica were subjected to the detection of canine filarioids by four different
methods: the microhematocrit tube test (MCT), Knott's modified test, serology and
a high resolution melt and quantitative real-time PCR (HRM-qPCR). Co-infection
with other vector-borne pathogens was also evaluated. RESULTS: Fifteen percent of
the dogs were positive to Dirofilaria immitis by at least one of the methods. The
HRM-qPCR produced distinctive melting plots for the different filarial worms and
revealed that 11.6% of dogs were infected with Acanthocheilonema reconditum. The
latter assay had a limit of detection of 2.4x10-4 mf/MUl and detected infections
with lower microfilarial concentrations in comparison to the microscopic
techniques and the serological assay. The MCT and Knott's test only detected dogs
with D. immitis microfilaremias above 0.7 mf/MUl. Nevertheless, there was a
strong correlation between the microfilarial concentration obtained by the
Knott's modified test and the HRM-qPCR (r = 0.906, p < 0.0001). Interestingly,
one dog was found infected with Cercopithifilaria bainae infection. Moreover, no
association was found between microfilaremia and co-infection and there was no
significant difference in microfilarial concentration between dogs infected only
with D. immitis and dogs co-infected with Ehrlichia canis, Anaplasma platys or
Babesia vogeli. CONCLUSIONS: This is the first report of A. reconditum and C.
bainae in Costa Rica and Central America. Among the evaluated diagnostic
techniques, the HRM-qPCR showed the most sensitive and reliable performance in
the detection of blood filaroids in comparison to the Knott's modified test, the
MCT test and a serological assay.
PMID- 25851921
TI - Molecular cytogenetic characterization of a 2q35-q37 duplication and a 4q35.1
q35.2 deletion in two cousins: a genotype-phenotype analysis.
AB - The 2q3 duplication and 4q3 deletion are two distinct conditions with variable
phenotypes including developmental delay, intellectual disability, Pierre Robin
sequence (PRS), and cardiovascular, craniofacial, digital and skeletal anomalies.
We describe two cousins, a 37-year-old man (Patient 1) and a 17-year-old girl
(Patient 2), with a derivative chromosome leading to a 4q35 deletion-2q35q37
duplication. Conventional karyotype showed in both patients the same
rearrangement derived from unbalanced segregation of a parental reciprocal
translocation involving the long arms of chromosome 2 and 4. Patient 1's father
and Patient 2's mother were identified as the carriers of a balanced
translocation t(2;4)(q35;q35). Array-CGH analysis, performed to characterize the
rearrangement, documented in both patients the presence of a 26 Mb duplication of
the 2q35-q37.3 region of chromosome 2 and a 6.3 Mb deletion of the 4q35.1-q35.2
region of chromosome 4. Both patients showed intellectual disability, minor
facial, and digital anomalies, hearing, ocular, and genitourinary abnormalities.
The comparison of their features with those of published cases of 2q3 duplication
and 4q3 deletion allowed us to further delineate the genotype-phenotype
correlation as well as the combined effect of partial 2q duplication and 4q
deletion syndromes in adulthood.
PMID- 25851922
TI - Ultrasensitive Molecular Beacon Designed with Totally Serinol Nucleic Acid (SNA)
for Monitoring mRNA in Cells.
AB - An artificial nucleic acid based on acyclic serinol building blocks and termed
"serinol nucleic acid" (SNA) was used to construct a fluorescent probe for RNA
visualization in cells. The molecular beacon (MB) composed of only SNA with a
fluorophore at one terminus and a quencher at the other was resistant to
enzymatic digestion, due to its unnatural acyclic scaffold. The SNA-MB could
detect its complementary RNA with extremely high sensitivity; the signal-to
background (S/B) ratio was as high as 930 when perylene and anthraquinone were
used as the fluorophore and quencher pair. A high S/B ratio was also achieved
with SNA-MB tethering the conventional Cy3 fluorophore, and this probe enabled
selective visualization of target mRNA in fixed cells. Thus, SNA-MB has potential
for use as a biological tool capable of visualizing RNA in living cells.
PMID- 25851923
TI - High-grade fetal adenocarcinoma of the lung is a tumour with a fetal phenotype
that shows diverse differentiation, including high-grade neuroendocrine
carcinoma: a clinicopathological, immunohistochemical and mutational study of 20
cases.
AB - AIMS: High-grade fetal adenocarcinoma (H-FLAC) is a rare variant of pulmonary
adenocarcinoma; this study aims to elucidate its clinicopathological features and
genetic abnormalities. METHODS AND RESULTS: Clinicopathological,
immunohistochemical and mutational analyses were performed on 20 surgically
resected lung cancers that showed H-FLAC histology in various proportions. These
tumours predominantly occurred in elderly males and in 10 patients who were heavy
smokers. Four cases were pure H-FLAC, and 16 cases were mixed H-FLAC, which were
found to be combined with conventional-type adenocarcinoma (15 cases), large-cell
neuroendocrine carcinoma (three cases), small-cell carcinoma (one case), enteric
adenocarcinoma (two cases), choriocarcinoma (two cases), and a solid-clear cell
pattern (seven cases). The fetal phenotype and diverse differentiation were
supported by the immunoexpression of alpha-fetoprotein (95%), thyroid
transcription factor-1 (TTF-1) (50%), neuroendocrine markers (30-45%), proneural
markers (50-69%), and CDX2 (40%). Except for TTF-1 expression (pure H-FLACs, 0%;
mixed H-FLACs, 63%), there were no significant differences in histological or
immunohistochemical findings between pure and mixed H-FLACs. EGFR, KRAS, BRAF and
PIK3CA mutations were identified in 20%, 0%, 0% and 7% of the tumours,
respectively. CONCLUSIONS: Lung adenocarcinomas with H-FLAC features possess the
potential for multidirectional differentiation, and are not strongly associated
with known major driver gene mutations.
PMID- 25851924
TI - Sanfilippo syndrome: Overall review.
AB - Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal
storage disorder, caused by a deficiency in one of the four enzymes involved in
the catabolism of glycosaminoglycan heparan sulfate. It is characterized by
progressive cognitive decline and severe hyperactivity, with relatively mild
somatic features. This review focuses on clinical features, diagnosis, treatment,
and follow-up of MPS III, and provides information about supplementary tests and
differential diagnosis. Given that few reviews of MPS III have been published,
several studies were compiled to establish diagnostic recommendations.
Quantitative urinary glycosaminoglycan analysis is strongly recommended, and
measurement of disaccharides, heparin cofactor II-thrombin complex and
gangliosides is also used. Enzyme activity of the different enzymes in blood
serum, leukocytes or fibroblasts, and mutational analysis for SGSH, NAGLU, HGSNAT
or GNS genes are required to confirm diagnosis and differentiate four subtypes of
MPS III. Although there is no global consensus for treatment, enzyme replacement
therapy and gene therapy can provide appropriate results. In this regard, recent
publications on treatment and follow-up are discussed.
PMID- 25851925
TI - Acute aortic syndromes: current status.
AB - The term acute aortic syndrome comprises aortic dissection, intramural hematoma,
and penetrating atherosclerotic ulcer. The most recent developments in acute
aortic syndromes include (1) a change in the mindset that each entity is
pathologically distinct, with a shift toward considering the acute aortic
syndromes as points along a spectrum of aortic disease, (2) the optimization of
aortic imaging quality and radiation dose, and (3) surgical or endovascular
management. This review article focuses on how these developments pertain to
thoracic radiologists.
PMID- 25851926
TI - Diet inclusion of devil fish (Plecostomus spp.) silage and its impacts on ruminal
fermentation and growth performance of growing lambs in hot regions of Mexico.
AB - The aim of this study was to evaluate the inclusion of devil fish (Plecostomus
spp.-DF) silage in Criollo * Blackbelly lamb diets in hot region of Guerrero
state of Mexico. Rumen fermentation including pH, volatile fatty acids (VFA) and
ammonia-N (NH3-N) and productive variables including feed intake (FI), average
daily gain (ADG), and feed conversion were determined. Twenty lambs with 18 +/-
1.2 kg body weight in a completely randomized design were fed a total mixed
ration (TMR) of concentrate (based on soybean meal, whole oat hay, ground corn
cob, vitamins-minerals supplement) with DF silage at 0 % (DF0), 9 % (DF9), 18 %
(DF18), and 27 % (DF27) of the TMR for 75 days. The ruminal pH showed no
difference (P > 0.05) between treatments: ranging between 6.21 and 6.36.
Propionic acid molar proportions showed an irregular pattern between experimental
groups, which only differed (P < 0.05) between DF9 and DF27, without differences
between the other treatments. A greater molar proportion of butyric acid was
noted (P < 0.05) in DF27 when compared to the other treatments. The ruminal
concentration of NH3-N showed some insignificant differences (P > 0.05) among
treatments. The daily FI was increased (P < 0.01) in DF27 (1.131 g) when compared
with DF0, while DF9 and DF18 showed intermediate consumption with no differences
(P > 0.05) among them. The ADG showed only difference (cubic effect, P = 0.02)
between DF9 and DF18. The highest feed conversion was observed (cubic effect, P <
0.01) with DF18, with a value of 4.7 kg of feed to gain 1 kg of body weight. It
could be concluded that the inclusion of up to 18 % of DF silage in the TMR of
growing lamb diets, in hot regions of Mexico, may improve productive performance
and ruminal fermentation kinetics, without any negative effects.
PMID- 25851927
TI - Effects of processing corn on the carcass traits and meat quality of feedlot
lambs.
AB - The objectives of this study were to evaluate and compare the effect of the corn
grain processing (whole grain, dry beans ground, and wet grain) on carcass
characteristics and meat quality in lambs. Twenty-two Dorper vs. Santa Ines
uncastrated lambs (27 +/- 4 kg BW; +/-3 months old) were distributed in a
randomized complete block (initial BW). The diets were composed of 20 % protein
mineral pellet, 5 % hay, and 75 % corn in the form of whole grain, ground grain,
or wet grain. The harvest weight of animals fed whole corn (50.2 kg) and ground
(49.03 kg) were equal and higher than the moisture corn fed lambs (44.89 kg);
therefore, the same differences were expected to be seen in the cold vs hot
carcass comparison. However, there was no difference between treatments comparing
hot or cold carcass performance, averaging 47 and 46 %, respectively. Also
unaffected by the treatments were subcutaneous fat thickness values, loin muscle
area, pH, temperature, drip loss, water loss by cooking, color, and tenderness.
It can be concluded that the shape and size of corn grain in diets of high
concentrate resulted in no measurable influence on carcass traits, but whole
grain is more easily managed by the producer.
PMID- 25851928
TI - Relationships between heat stress and metabolic and milk parameters in dairy cows
in Southern Brazil.
AB - This study approached the relationships between heat stress and metabolic and
milk parameters in a commercial herd of Holstein cows located in southern Brazil.
A total of 50 multiparous cows at different lactations and lactation stages were
selected in order to obtain 450 samples during two consecutive years (2011 and
2012). The animals were fed a partial mixed ration along with ryegrass pasture in
a semi-confinement system. Blood, milk, and urine samples were taken during the
summer and winter for a total of eight samples. Three intervals of temperature
humidity index (THI) were established during the summer months (January and
February) as follows: low group (LOW), THI between 75 and 81 (N = 100); moderate
group (MOD), THI between 81 and 82 (N = 150); and severe group (SEV), THI between
83 and 90 (N = 150). The group of cows sampled during winter (July) constituted
the control group (CON; THI = 59, N = 50). Increased total protein, albumin,
glucose, and cholesterol occurred in heat-stressed cows. Increased AST activity
was also observed in heat-stressed cows, but triglycerides and beta-OH-butyrate
did not show any difference among groups. Lower lactate and higher pO2 were seen
in cows with heat stress than CON. Cows in SEV had a 21 % milk yield decrease,
while lactose and protein decreased with fat not being affected. Heat stress had
strong effects on metabolic, clinical, and performance parameters in Holstein
cows.
PMID- 25851929
TI - "Ormilo disease" a disorder of zebu cattle in Tanzania: bovine cerebral
theileriosis or new protozoan disease?
AB - "Ormilo" disease is a neurological disorder of cattle described by Maasai herders
in Tanzania. It is attributed to infection by Theileria species, although no
detailed data are available in the literature. The authors describe the
macroscopical and histological changes observed in 30 brains of indigenous short
horn zebu cattle from Northern Tanzania, aged 2-9 years, with the characteristic
neurological signs of "Ormilo". Moreover, the ultrastructural details observed in
14 selected brain samples were reported. Areas of congestion and hemorrhages,
associated with the obstruction of the cerebral vessels with large numbers of
parasitized lymphoid cells, were observed. Electron microscopy showed the
presence of intralymphocytic parasites morphologically comparable to flagellated
protozoa, not previously described in the lymphoid cells of cattle, but only
reported during the sexual stages within the vector. Theileria taurotragi was
detected by polymerase chain reaction (PCR) and reverse line blot (RLB) in nine
samples. The authors hypothesize that the parasite detected by electron
microscopy could be a strain of a Theileria endemic to this region till now not
investigated, having an intralymphocytic phase and being associated with other
Theileria spp. infestation. Further studies are needed to better understand the
etiology of "Ormilo" disease and to characterize the morphology of the observed
parasite, clarifying its role in the disease in Tanzania.
PMID- 25851930
TI - Improving rumen ecology and microbial population by dried rumen digesta in beef
cattle.
AB - Four Thai native beef cattle with initial body weight (BW) of 91.8 +/- 4.75 kg
were randomly assigned according to a 4 * 4 Latin square design to receive four
concentrates replacement levels of soybean meal (SBM) by dried rumen digesta
(DRD) at 0, 33, 67, and 100 % on dry matter (DM) basis. All cattle were fed rice
straw ad libitum while additional concentrate was fed at 0.5 % BW daily. The
experiment was conducted for four periods of 21 days. Rumen fluid was analyzed
for predominant cellulolytic bacterial population by using real-time PCR
technique. Increasing levels of DRD did not alter total feed intake, ruminal pH
and temperature, and plasma urea nitrogen (P > 0.05). Protozoa and fungal
population were not differed by DRD supplementation while population of bacteria
at 4 h post feeding was increased when SBM was replaced with DRD at 66 and 100 %
DM. Population of total bacteria and R. flavefaciens at 4 h post feeding were
significantly highest with inclusion of 100 % of DRD in the ration. The
experimental diets has no effect on excretion and absorption of purine
derivatives (P > 0.05), while microbial crude protein and efficiency of microbial
N synthesis were significantly increased with DRD inclusion in the diet and
highest with 100 % DRD replacement (P > 0.05). Replacement of SBM by DRD at 100 %
DM improved the rumen ecology and microbial population in beef cattle fed on rice
straw.
PMID- 25851931
TI - Factors affecting response to proton pump inhibitor therapy in patients with
gastroesophageal reflux disease: a multicenter prospective observational study.
AB - BACKGROUND: Proton pump inhibitor (PPI) therapy, the first-line treatment for
gastroesophageal reflux disease (GERD), is not always effective. This study aimed
to examine the effect of pretreatment patient characteristics on response to PPI
therapy. METHODS: Japanese outpatients with symptomatic GERD scheduled to receive
endoscopy and PPI therapy were enrolled in this multicenter prospective
observational study. The patients' characteristics, including GERD and dyspeptic
symptoms, anxiety, depression, and quality of life, were assessed using
questionnaires before and 2 and 4 weeks after the start of PPI therapy. Factors
affecting therapeutic response were examined by simple and multiple regression
analyses using three patient-reported outcome measures as objective variables.
RESULTS: Data from 182 patients were analyzed. In multiple regression analysis
using the residual symptom rate as an objective variable, lower GERD symptom
score (p < 0.05), absence of erosive esophagitis (p < 0.05), higher epigastric
pain/burning symptom score (p < 0.05), and higher depression subscale score (p <
0.05) accompanied poorer therapeutic response. In analyses using the patient's
impression of therapy, lower GERD symptom score (p < 0.05) and absence of erosive
esophagitis (p < 0.05) accompanied poorer therapeutic response. In analyses using
the relative GERD symptom intensity evaluated using a numeric rating scale, lower
GERD symptom score (p < 0.05), higher epigastric pain/burning symptom score (p <
0.1), and lower body mass index (p < 0.05) accompanied poorer therapeutic
response. CONCLUSIONS: Patients who complained of milder GERD symptoms before
treatment were likely to have poorer response to PPI therapy. Association of
absence of erosive esophagitis, severer epigastric pain/burning symptoms, lower
body mass index, and severer depression with poorer therapeutic response was also
suggested.
PMID- 25851933
TI - Estimating time-varying RSA to examine psychophysiological linkage of marital
dyads.
AB - One of the primary tenets of polyvagal theory dictates that parasympathetic
influence on heart rate, often estimated by respiratory sinus arrhythmia (RSA),
shifts rapidly in response to changing environmental demands. The current
standard analytic approach of aggregating RSA estimates across time to arrive at
one value fails to capture this dynamic property within individuals. By utilizing
recent methodological developments that enable precise RSA estimates at smaller
time intervals, we demonstrate the utility of computing time-varying RSA for
assessing psychophysiological linkage (or synchrony) in husband-wife dyads using
time-locked data collected in a naturalistic setting.
PMID- 25851932
TI - Ultrasound molecular imaging: Moving toward clinical translation.
AB - Ultrasound is a widely available, cost-effective, real-time, non-invasive and
safe imaging modality widely used in the clinic for anatomical and functional
imaging. With the introduction of novel molecularly-targeted ultrasound contrast
agents, another dimension of ultrasound has become a reality: diagnosing and
monitoring pathological processes at the molecular level. Most commonly used
ultrasound molecular imaging contrast agents are micron sized, gas-containing
microbubbles functionalized to recognize and attach to molecules expressed on
inflamed or angiogenic vascular endothelial cells. There are several potential
clinical applications currently being explored including earlier detection,
molecular profiling, and monitoring of cancer, as well as visualization of
ischemic memory in transient myocardial ischemia, monitoring of disease activity
in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a
first clinical grade ultrasound contrast agent (BR55), targeted at a molecule
expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2;
VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted
ultrasound imaging is being explored in first inhuman clinical trials in various
cancer types. This review describes the design of ultrasound molecular imaging
contrast agents, imaging techniques, and potential future clinical applications
of ultrasound molecular imaging.
PMID- 25851934
TI - Hematopoietic progenitor cells collection in pediatric patients with brain tumor.
AB - AIM: To analyze the efficacy and safety of hematopoietic progenitor cells (HPC)
collections by leukapheresis in pediatric patients with brain tumors. RESULTS:
Between 2003 and 2014, we collected HPC from 19 children (12 boys/7 girls),
median age at the diagnosis of 5 years old (<1-15 years old) and weight of 16.8
Kg (6.7-42). Diagnoses were Medulloblastoma (n = 10), Primitive Neuroectodermal
Tumor (n = 5), Atypical Teratoid Rhabdoid Tumor (n = 3) and Secreting Germ Cell
Tumor (n = 1). All patients performed leukapheresis by a central venous catheter,
at the fifth day of mobilization with G-CSF (median dose 11.7 ug/Kg/day), 9 of
them with COBE(r) Spectra and 10 with Spectra Optia(r). The anticoagulant used
was ACD-A, ratio of 14:1 or ACD-A plus heparin, ratio 25:1. The tubing set was
primed with a compatible, irradiated, leukodepleted and hematocrit adjusted
packed red cells for all children <30 kg (n = 17). A median of 1.5 (1-3)
leukapheresis per patient was performed with an average of 3 (1.5-5.4) blood
volumes processed; 3 children did a second mobilization and one additional
leukapheresis. The median number of CD34+ cells collected was 4.6 * 10(6) /Kg
(0.18-22.6) of patient body weight; 12 children collected for a tandem
transplant. The median time between cell collection and infusion was 3 (0.6-9.1)
months. CONCLUSIONS: HPC collection in children is an efficient and well
tolerated technique, performed as an outpatient procedure. With the new
mobilization schemes and leukapheresis technology, we can collect a high number
of HPC allowing pediatric oncologist to establish more aggressive chemotherapy
protocols hoping to improve patient outcome.
PMID- 25851936
TI - Osteocytes and Homeostasis of Remote Organs : Bone-Buried Osteocytes Talk to
Remote Organs.
AB - The study of bones has attracted researchers from many medical fields. To
understand bone-organ interactions, hematologists were challenged to investigate
bone marrow (BM), the core of bone where hematopoiesis takes place. Through
studies of the hematopoietic stem cells niche, hematologists contributed to the
discovery of unexpected functions of bone-forming osteoblasts and bone-buried
osteocytes. In particular, the recent findings about osteocytes, as the
regulatory system of lympho-hematopoiesis and fat metabolism, highlighted the
central role of skeletal tissue in inter-organ communication. The cross-cutting
consideration including hematology and many other fields will expand the bone
research.
PMID- 25851935
TI - GNAS Spectrum of Disorders.
AB - The GNAS complex locus encodes the alpha-subunit of the stimulatory G protein
(Gsalpha), a ubiquitous signaling protein mediating the actions of many hormones,
neurotransmitters, and paracrine/autocrine factors via generation of the second
messenger cAMP. GNAS gives rise to other gene products, most of which exhibit
exclusively monoallelic expression. In contrast, Gsalpha is expressed
biallelically in most tissues; however, paternal Gsalpha expression is silenced
in a small number of tissues through as-yet-poorly understood mechanisms that
involve differential methylation within GNAS. Gsalpha-coding GNAS mutations that
lead to diminished Gsalpha expression and/or function result in Albright's
hereditary osteodystrophy (AHO) with or without hormone resistance, i.e.,
pseudohypoparathyroidism type-Ia/Ic and pseudo-pseudohypoparathyroidism,
respectively. Microdeletions that alter GNAS methylation and, thereby, diminish
Gsalpha expression in tissues in which the paternal Gsalpha allele is normally
silenced also cause hormone resistance, which occurs typically in the absence of
AHO, a disorder termed pseudohypoparathyroidism type-Ib. Mutations of GNAS that
cause constitutive Gsalpha signaling are found in patients with McCune-Albright
syndrome, fibrous dysplasia of bone, and different endocrine and non-endocrine
tumors. Clinical features of these diseases depend significantly on the parental
allelic origin of the GNAS mutation, reflecting the tissue-specific paternal
Gsalpha silencing. In this article, we review the pathogenesis and the phenotypes
of these human diseases.
PMID- 25851937
TI - Disease characteristics, treatment patterns, prognosis, outcomes and lymphoma
related mortality in elderly follicular lymphoma in the United States.
AB - Data from the National LymphoCare Study (a prospective, multicentre registry that
enrolled follicular lymphoma (FL) patients from 2004 to 2007) were used to
determine disease characteristics, treatment patterns, outcomes and prognosis for
elderly FL (eFL) patients. Of 2650 FL patients, 209 (8%) were aged >80 years;
these eFL patients more commonly had grade 3 disease, less frequently received
chemoimmunotherapy and anthracyclines, and had lower response rates when compared
to younger patients. With a median follow-up of 6.9 years, 5-year overall
survival (OS) for eFL patients was 59%; 38% of deaths were lymphoma-related. No
treatment produced superior OS among eFL patients. In multivariate Cox models,
anaemia, B-symptoms and male sex predicted worse OS (P < 0.01); a prognostic
index of these factors (0, 1 or >= 2 present) predicted OS [hazard ratio (95%
CI): >= 2 vs. 0, 4.72 (2.38-9.33); 1 vs. 0, 2.63 (1.39-4.98)], with a higher
concordance index (0.63) versus the Follicular Lymphoma International Prognostic
Index (0.55). The index was validated in an independent cohort. In the largest
prospective US-based eFL cohort, no optimal therapy was identified and nearly 40%
of deaths were lymphoma-related, representing baseline outcomes in the modern
era.
PMID- 25851939
TI - Structural insight of glitazone for hepato-toxicity: Resolving mystery by PASS.
AB - Troglitazone causes severe hepatic injury in certain individuals and multiple
mechanisms related to hepato-toxicity has been reported creating confusion. In
the present study, the mechanism for the hepatic injury of glitazones was
investigated by PASS. The results suggest that chromane containing glitazones are
apoptic agonist (activating p53 by intrinsic pathway leading to the apoptosis)
and those which do not contain the chromane are devoid of this. In case of hepato
toxicity by non-chromane glitazone and their metabolite such as M-3, RM-3,
rosiglitazone and pioglitazone; PASS suggest that these chemicals are not apoptic
agonist but they are the substrate for CYP enzyme (Phase-I Oxidative Enzyme) and
Phase-II conjugating enzymes; interfering with bile acid metabolism rendering
bile acid more toxic (cholestasis). This unmetabolised bile salt further
initiates the process apoptosis via intrinsic and extrinsic pathway leading to
the apoptosis. Immunoblot analysis further confirm our hypothesis that
troglitazone (chromane containing glitazone), but not rosiglitazone and
pioglitazone (non-chromane containing glitazone) increased the levels of p53 in a
time-dependent manner. Hence our prediction related to the mechanism of hepato
toxicity by apoptosis and structural insight of glitazone can be helpful in
improving the drug profile of this category.
PMID- 25851938
TI - Tricyclic 1,5-naphthyridinone oxabicyclooctane-linked novel bacterial
topoisomerase inhibitors as broad-spectrum antibacterial agents-SAR of left-hand
side moiety (Part-2).
AB - Novel bacterial topoisomerase inhibitors (NBTIs) represent a new class of broad
spectrum antibacterial agents targeting bacterial Gyrase A and ParC and have
potential utility in combating antibiotic resistance. A series of novel
oxabicyclooctane-linked NBTIs with new tricyclic-1,5-naphthyridinone left hand
side moieties have been described. Compounds with a (R)-hydroxy-1,5
naphthyridinone moiety (7) showed potent antibacterial activity (e.g.,
Staphylococcus aureus MIC 0.25 MUg/mL), acceptable Gram-positive and Gram
negative spectrum with rapidly bactericidal activity. The compound 7 showed
intravenous and oral efficacy (ED50) at 3.2 and 27 mg/kg doses, respectively, in
a murine model of bacteremia. Most importantly they showed significant
attenuation of functional hERG activity (IC50 >170 MUM). In general, lower logD
attenuated hERG activity but also reduced Gram-negative activity. The co-crystal
structure of a hydroxy-tricyclic NBTI bound to a DNA-gyrase complex exhibited a
binding mode that show enantiomeric preference for R isomer and explains the
activity and SAR. The discovery, synthesis, SAR and X-ray crystal structure of
the left-hand-side tricyclic 1,5-naphthyridinone based oxabicyclooctane linked
NBTIs are described.
PMID- 25851940
TI - Development of methyl isoxazoleazepines as inhibitors of BET.
AB - In this report we detail the evolution of our previously reported thiophene
isoxazole BET inhibitor chemotype exemplified by CPI-3 to a novel bromodomain
selective chemotype (the methyl isoxazoleazepine chemotype) exemplified by
carboxamide 23. The methyl isoxazoleazepine chemotype provides potent inhibition
of the bromodomains of the BET family, excellent in vivo PK across species, low
unbound clearance, and target engagement in a MYC PK-PD model.
PMID- 25851941
TI - Making water-soluble integral membrane proteins in vivo using an amphipathic
protein fusion strategy.
AB - Integral membrane proteins (IMPs) play crucial roles in all cells and represent
attractive pharmacological targets. However, functional and structural studies of
IMPs are hindered by their hydrophobic nature and the fact that they are
generally unstable following extraction from their native membrane environment
using detergents. Here we devise a general strategy for in vivo solubilization of
IMPs in structurally relevant conformations without the need for detergents or
mutations to the IMP itself, as an alternative to extraction and in vitro
solubilization. This technique, called SIMPLEx (solubilization of IMPs with high
levels of expression), allows the direct expression of soluble products in living
cells by simply fusing an IMP target with truncated apolipoprotein A-I, which
serves as an amphipathic proteic 'shield' that sequesters the IMP from water and
promotes its solubilization.
PMID- 25851943
TI - Linearly tunable emission colors obtained from a fluorescent-phosphorescent dual
emission compound by mechanical stimuli.
AB - Organic mechanoluminochromic materials are mechano/piezo-responsive and promising
for applications in sensors, displays, and data storage devices. However, their
switching range of emission is seriously impeded by only one kind of emission
(either a fluorescent or phosphorescent peak) in the spectrum of single organic
compounds. This study presents a design strategy for pure organic compounds with
excellent room-temperature fluorescent-phosphorescent dual-emission (rFPDE)
properties, which combines the effective factors of dipenylsulfone group,
crystalline state, and heavy atom effect. Following the principle of color
mixing, myriad emission colors with a wide range from orange to purple and across
white zone in a straight line in the chromaticity diagram of the Commission
Internationale de l'Eclairage (CIE) can be obtained by simply mechanical grinding
the compound. The unique properties could be concentrated on a pure organic
compound through this design strategy, which provides a new efficient channel for
the discovery of efficient mechano-responsive organic materials.
PMID- 25851942
TI - A phase II study of perioperative S-1 combined with weekly docetaxel in patients
with locally advanced gastric carcinoma: clinical outcomes and
clinicopathological and pharmacogenetic predictors for survival.
AB - BACKGROUND: We conducted a phase II study to evaluate the efficacy and safety of
perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to
investigate the association between CYP2A6 genotype and outcome. METHODS:
Patients with LAGC [clinical stage III-IV (M0) by the Japanese staging system]
received three cycles of pre- and postoperative chemotherapy (S-1 40 mg/m(2)
twice daily on days 1-14; intravenous docetaxel 35 mg/m(2) on days 1 and 8, every
3 weeks) followed by gastrectomy with D2 dissection. We also performed a
pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1.
RESULTS: From October 2006 to June 2008, 44 patients entered the study. 43
eligible patients completed preoperative chemotherapy and 40 completed
postoperative chemotherapy. The most common G3/4 toxicities during pre- and
postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The
clinical response rate by RECIST was 74.4 % (95 % CI, 61.4-87.4 %), and the R0
resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of
patients. The 3-year progression-free survival (PFS) rate was 62.8 % and 5-year
overall survival (OS) rate was 69.6 %. PFS and OS differed significantly
according to clinical response, clinical downstaging, and CYP2A6 genotype.
Patients with CYP2A6 variant/variant genotypes had a higher tegafur C max and
worse survival than those with wild/wild or wild/variant genotypes. CONCLUSION:
Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients
with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging,
and CYP2A6 genotype may predict efficacy.
PMID- 25851944
TI - Cell type-specific in vivo expression of genes encoding signalling molecules in
the brain in response to chronic mild stress and chronic treatment with
fluoxetine.
AB - RATIONALE: Previously, we reported that chronic treatment with fluoxetine
increased gene expression of 5-hydroxytryptamine receptor 2B (5-HT2BR), cytosolic
phospholipase 2alpha (cPLA2alpha), glutamate receptor, ionotropic kainate 2
(GluK2) and adenosine deaminase acting on RNA 2 (ADAR2), in cultured astrocytes
and astrocytes freshly isolated from transgenic mice tagged with an astrocyte
specific marker. In contrast, neurones isolated from transgenic mice tagged with
a neurone-specific marker and exposed to fluoxetine showed an increase in gene
expression of glutamate receptor, ionotropic kainate 4 (GluK4) and 5
hydroxytryptamine receptor 2C (5-HT2CR). In a mouse model of anhedonia, the
downregulation of 5-HT2BR, cPLA2alpha, ADAR2 and GluK4 but not GluK2 and 5-HT2CR
was detected. OBJECTIVE: To investigate the effects of chronic mild stress (CMS)
and/or fluoxetine treatment on gene expression of 5-HT2BR, 5-HT2CR, cPLA2alpha,
ADAR2, GluK2 and GluK4 specifically in astrocytes and neurones. METHODS:
Transgenic mice tagged with either astrocyte- or neurone-specific markers were
exposed to the CMS. Real-time PCR was applied to determine expression of
messenger RNA (mRNA). RESULTS: We found that (i) mRNAs of the 5-HT2BR and
cPLA2alpha in astrocytes and GluK4 in neurones were significantly reduced in mice
that became anhedonic; the mRNA levels were restored by fluoxetine treatment;
(ii) ADAR2 in astrocytes was decreased by the CMS but showed no response to
fluoxetine in anhedonic animals; (iii) neither GluK2 expression in astrocytes nor
5-HT2CR expression in neurones were affected in anhedonic animals, although
expression of 5-HT2CR mRNA was upregulated by fluoxetine. CONCLUSIONS: Our
results indicate that the effects of chronic treatment with fluoxetine are not
only dependent on the cell type studied but also on the development of anhedonia.
This suggests that fluoxetine may affect major depression (MD) patients and
healthy people in a different manner.
PMID- 25851946
TI - Cecal diverticulitis is a challenging diagnosis: a report of 3 cases.
AB - BACKGROUND: Cecal diverticulitis is an uncommon cause of acute abdominal pain and
presents clinically similar to acute appendicitis. There are many perspectives
concerning the management of this condition, ranging from different types of
surgical resections to conservative treatment with antibiotics. CASE REPORT: We
present 3 cases of cecal diverticulitis. One of the patients was treated
conservatively with intravenous antibiotics and the other 2 were treated with
surgical resection. CONCLUSIONS: Conservative treatment with intravenous
antibiotics can be used in uncomplicated cecal diverticulitis. Complicated cecal
diverticulitis is managed surgically and the type of resection depends mainly on
the extent of inflammation.
PMID- 25851945
TI - Knowledge, Attitudes, and Practice Regarding Genetic Testing and Genetic
Counselors in Jordan: A Population-Based Survey.
AB - Genetic testing has a potential in the prevention of genetic diseases,
particularly in communities with high rates of consanguineous marriage.
Therefore, knowledge, practice, and attitudes of the public in Jordan regarding
genetic testing were investigated. Individuals (N = 3,196) were questioned about
the concepts of genetic testing and genetic counselors, if they underwent any
genetic tests, the type of test, the method of consenting to the test, as well as
their level of satisfaction with the privacy of the genetic testing service. The
likelihood of pursuing predictive genetic testing for cancer was also
investigated. Although almost 70 % of respondents knew the term "genetic
testing," only 18 % had undergone genetic testing, primarily the mandatory
premarital test. In addition, there was a lack of general knowledge about genetic
counselors. Many of those who had genetic testing (45 %) indicated they did not
go through a consent process, and a lack of consent was significantly related to
dissatisfaction with the privacy of the service. Approximately 55 % of
respondents indicated they would potentially pursue predictive genetic testing
for cancer. Going for routine health checkups was not significantly correlated
with either actual or potential uptake of genetic testing, suggesting health care
providers do not play an influential role in patients' testing decisions. Our
results show a gap between the knowledge and uptake of genetic testing and may
help to guide the design of effective strategies to initiate successful genetic
counseling and testing services.
PMID- 25851947
TI - A call for statistical editors in ecology.
PMID- 25851948
TI - Managing older adults with ground-level falls admitted to a trauma service: the
effect of frailty.
AB - OBJECTIVES: To determine whether frail elderly adults are at greater risk of
fracture after a ground-level fall (GLF) than those who are not frail. DESIGN:
Prospective observational study. SETTING: Level 1 trauma center. PARTICIPANTS:
All elderly (>=65) adults presenting after a GLF over 1 year (N = 110; mean age
+/- SD 79.5 +/- 8.3, 54% male). MEASUREMENT: A Frailty Index (FI) was calculated
using 50 preadmission frailty variables. Participants with a FI of 0.25 or
greater were considered to be frail. The primary outcome measure was a new
fracture; 40.1% (n = 45) of participants presented with a new fracture. The
secondary outcome was discharge to an institutional facility (rehabilitation
center or skilled nursing facility). Multivariate logistic regression was
performed. RESULTS: Forty-three (38.2%) participants were frail. The median
Injury Severity Score was 14 (range 9-17), and the mean FI was 0.20 +/- 0.12.
Frail participants were more likely than those who were not frail to have
fractures (odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.2-2.3, P =
.01). Thirty-six (32.7%) participants were discharged to an institutional
facility. Frail participants were more likely to be discharged to an
institutional facility (OR = 1.42, 95% CI = 1.08-3.09, P = .03) after a GLF.
CONCLUSION: Frail individuals have a higher likelihood of fractures and discharge
to an institutional facility after a GLF than those who are not frail. The FI may
be used as an adjunct for decision-making when developing a discharge plan for an
elderly adult after a GLF.
PMID- 25851949
TI - PROVEAN web server: a tool to predict the functional effect of amino acid
substitutions and indels.
AB - We present a web server to predict the functional effect of single or multiple
amino acid substitutions, insertions and deletions using the prediction tool
PROVEAN. The server provides rapid analysis of protein variants from any
organisms, and also supports high-throughput analysis for human and mouse
variants at both the genomic and protein levels. AVAILABILITY AND IMPLEMENTATION:
The web server is freely available and open to all users with no login
requirements at http://provean.jcvi.org. CONTACT: achan@jcvi.org SUPPLEMENTARY
INFORMATION: Supplementary data are available at Bioinformatics online.
PMID- 25851950
TI - Characterization of a flavin-containing monooxygenase from Corynebacterium
glutamicum and its application to production of indigo and indirubin.
AB - OBJECTIVE: To examine the role of a gene encoding flavin-containing monooxygenase
(cFMO) from Corynebacterium glutamicum ATCC13032 when cloned and expressed in
Escherichia coli for the production of indigo pigments. RESULTS: The blue
pigments produced by recombinant E. coli were identified as indigo and indirubin.
The cFMO was purified as a fused form with maltose-binding protein (MBP). The
enzyme was optimal at 25 degrees C and pH 8. From absorption spectrum analysis,
the cFMO was classified as a flavoprotein. FMO activity was strongly inhibited by
1 mM Cu(2+) and recovered by adding 1-10 mM EDTA. The enzyme catalyzed the
oxidation of TMA, thiourea, and cysteamine, but not glutathione or cysteine. MBP
cFMO had an indole oxygenase activity through oxygenation of indole to indoxyl.
The recombinant E. coli produced 685 mg indigo l(-1) and 103 mg indirubin l(-1)
from 2.5 g L-tryptophan l(-1). CONCLUSION: The results suggest the cFMO can be
used for the microbial production of both indigo and indirubin.
PMID- 25851951
TI - Activin A can induce definitive endoderm differentiation from human
parthenogenetic embryonic stem cells.
AB - OBJECTIVES: As activin/nodal signaling plays a key role in definitive endoderm
(DE) differentiation, we have explored activin A-induced differentiation of DE
from human parthenogenetic embryonic stem cells (hPESCs). RESULTS: Administration
of 5 ng activin A/ml had no effect on the expression of markers of DE
differentiation. However, higher concentrations of activin A (50 and 100 ng/ml)
upregulated Sox17 and Cxcr4, as well upregulating the mesendodermal precursor
marker, Brachyury. CONCLUSIONS: These findings demonstrate that low dose activin
A can maintain the undifferentiated potency of hPESCs, whereas higher doses
induce DE differentiation; 50 ng/ml is the optimal concentration for inducing DE
from hPESCs.
PMID- 25851952
TI - Enzymatic synthesis of aroma acetoin fatty acid esters by immobilized Candida
antarctica lipase B.
AB - OBJECTIVE: To enzymatically synthesize aroma acetoin fatty acid esters, useful as
flavor and fragrance ingredients in foods. RESULTS: Immobilized Candida
antarctica lipase B (CALB), performed significantly better than lipases from
Rhizopus niveus and Candida rugosa in carrying out the esterification of acetoin
and fatty acids. C4-C12 straight chain fatty acids were suitable acyl donors and
CALB had a strong preference for longer straight chains up to ten carbon atoms.
Higher temperatures, 40-60 degrees C, and higher acetoin/fatty acid molar ratios
favored the conversion. The maximum yield of acetoin octanoate obtained was (51
+/- 1) % after 24 h reaction time in hexane with 0.25 M octanoic acid, 5:1 excess
acetoin and an enzyme concentration of 6 g/mol fatty acid at 60 degrees C. The
enzyme activity declined at a steady rate during reuse at 60 degrees C and after
the 10th cycle, 65 % of initial activity was still be retained. CONCLUSION: This
is the first report of acetoin fatty acid ester synthesis by biological method
and CALB has been shown to be effective for the lipase-catalyzed esterification
of acetion and C4-C12 straight chain fatty acids.
PMID- 25851953
TI - Whole genome sequences in pulse crops: a global community resource to expedite
translational genomics and knowledge-based crop improvement.
AB - Unprecedented developments in legume genomics over the last decade have resulted
in the acquisition of a wide range of modern genomic resources to underpin
genetic improvement of grain legumes. The genome enabled insights direct
investigators in various ways that primarily include unearthing novel structural
variations, retrieving the lost genetic diversity, introducing novel/exotic
alleles from wider gene pools, finely resolving the complex quantitative traits
and so forth. To this end, ready availability of cost-efficient and high-density
genotyping assays allows genome wide prediction to be increasingly recognized as
the key selection criterion in crop breeding. Further, the high-dimensional
measurements of agronomically significant phenotypes obtained by using new
generation screening techniques will empower reference based resequencing as well
as allele mining and trait mapping methods to comprehensively associate genome
diversity with the phenome scale variation. Besides stimulating the forward
genetic systems, accessibility to precisely delineated genomic segments reveals
novel candidates for reverse genetic techniques like targeted genome editing. The
shifting paradigm in plant genomics in turn necessitates optimization of crop
breeding strategies to enable the most efficient integration of advanced omics
knowledge and tools. We anticipate that the crop improvement schemes will be
bolstered remarkably with rational deployment of these genome-guided approaches,
ultimately resulting in expanded plant breeding capacities and improved crop
performance.
PMID- 25851954
TI - Efficient and simple electro-transformation of intact cells for the
basidiomycetous fungus Pseudozyma hubeiensis.
AB - OBJECTIVE: An electroporation procedure for the species was investigated to
develop an efficient transformation method for the basidiomycetous fungus
Pseudozyma hubeiensis SY62, a strong biosurfactant-producing host. RESULTS: A
plasmid, pUXV1emgfp including green fluorescence protein as a reporter gene, was
constructed to determine the transformation and expression of foreign genes.
Optimal electroporation conditions achieved 44.8 transformants MUg(-1) plasmid
competency (intact cells) without protoplast treatment. Lithium acetate
treatments increased the efficiency to approx. Twice that of control experiments.
Almost all transformants demonstrated green fluorescence expressed in the
transformant cells. CONCLUSION: The optimal method, successfully applied to
several related species, yields sufficient transformant colonies to engineer the
host strain.
PMID- 25851955
TI - Assessing the treatment effect in a randomized controlled trial with extensive
non-adherence: the EVOLVE trial.
AB - Intention-to-treat (ITT) analysis is widely used to establish efficacy in
randomized clinical trials. However, in a long-term outcomes study where non
adherence to study drug is substantial, the on-treatment effect of the study drug
may be underestimated using the ITT analysis. The analyses presented herein are
from the EVOLVE trial, a double-blind, placebo-controlled, event-driven
cardiovascular outcomes study conducted to assess whether a treatment regimen
including cinacalcet compared with placebo in addition to other conventional
therapies reduces the risk of mortality and major cardiovascular events in
patients receiving hemodialysis with secondary hyperparathyroidism. Pre-specified
sensitivity analyses were performed to assess the impact of non-adherence on the
estimated effect of cinacalcet. These analyses included lag-censoring, inverse
probability of censoring weights (IPCW), rank preserving structural failure time
model (RPSFTM) and iterative parameter estimation (IPE). The relative hazard
(cinacalcet versus placebo) of mortality and major cardiovascular events was 0.93
(95% confidence interval 0.85, 1.02) using the ITT analysis; 0.85 (0.76, 0.95)
using lag-censoring analysis; 0.81 (0.70, 0.92) using IPCW; 0.85 (0.66, 1.04)
using RPSFTM and 0.85 (0.75, 0.96) using IPE. These analyses, while not providing
definitive evidence, suggest that the intervention may have an effect while
subjects are receiving treatment. The ITT method remains the established method
to evaluate efficacy of a new treatment; however, additional analyses should be
considered to assess the on-treatment effect when substantial non-adherence to
study drug is expected or observed.
PMID- 25851957
TI - Paternal Transmission of a Secondary Symbiont during Mating in the Viviparous
Tsetse Fly.
AB - Sodalis glossinidius, a maternally inherited secondary symbiont of the tsetse
fly, is a bacterium in the early/intermediate state of the transition toward
symbiosis, representing an important model for investigating establishment and
evolution of insect-bacteria symbiosis. The absence of phylogenetic congruence in
tsetse-Sodalis coevolution and the existence of Sodalis genotypic diversity in
field flies are suggestive for a horizontal transmission route. However, to date
no natural mechanism for the horizontal transfer of this symbiont has been
identified. Using novel methodologies for the stable fluorescent-labeling and
introduction of modified Sodalis in tsetse flies, we unambiguously show that male
borne Sodalis is 1) horizontally transferred to females during mating and 2)
subsequently vertically transmitted to the progeny, that is, paternal
transmission. This mixed mode of transmission has major consequences regarding
Sodalis' genome evolution as it can lead to coinfections creating opportunities
for lateral gene transfer which in turn could affect the interaction with the
tsetse host.
PMID- 25851958
TI - New Genetic Evidence Resolves Origins of Modern Japanese.
PMID- 25851956
TI - Adaptive Modifications of Muscle Phenotype in High-Altitude Deer Mice Are
Associated with Evolved Changes in Gene Regulation.
AB - At high-altitude, small mammals are faced with the energetic challenge of
sustaining thermogenesis and aerobic exercise in spite of the reduced O2
availability. Under conditions of hypoxic cold stress, metabolic demands of
shivering thermogenesis and locomotion may require enhancements in the oxidative
capacity and O2 diffusion capacity of skeletal muscle to compensate for the
diminished tissue O2 supply. We used common-garden experiments involving highland
and lowland deer mice (Peromyscus maniculatus) to investigate the transcriptional
underpinnings of genetically based population differences and plasticity in
muscle phenotype. We tested highland and lowland mice that were sampled in their
native environments as well as lab-raised F1 progeny of wild-caught mice.
Experiments revealed that highland natives had consistently greater oxidative
fiber density and capillarity in the gastrocnemius muscle. RNA sequencing
analyses revealed population differences in transcript abundance for 68 genes
that clustered into two discrete transcriptional modules, and a large suite of
transcripts (589 genes) with plastic expression patterns that clustered into five
modules. The expression of two transcriptional modules was correlated with the
oxidative phenotype and capillarity of the muscle, and these phenotype-associated
modules were enriched for genes involved in energy metabolism, muscle plasticity,
vascular development, and cell stress response. Although most of the individual
transcripts that were differentially expressed between populations were
negatively correlated with muscle phenotype, several genes involved in energy
metabolism (e.g., Ckmt1, Ehhadh, Acaa1a) and angiogenesis (Notch4) were more
highly expressed in highlanders, and the regulators of mitochondrial biogenesis,
PGC-1alpha (Ppargc1a) and mitochondrial transcription factor A (Tfam), were
positively correlated with muscle oxidative phenotype. These results suggest that
evolved population differences in the oxidative capacity and capillarity of
skeletal muscle involved expression changes in a small suite of coregulated
genes.
PMID- 25851959
TI - Real-time teleophthalmology in rural Western Australia.
AB - OBJECTIVE: This study aims to assess the current utilisation of a real-time
teleophthalmology service for rural Western Australia (WA). DESIGN: Service
evaluation by prospective audit. SETTING: Includes general practices,
optometrists, hospitals in rural WA and the Lions Eye Institute in Perth.
PARTICIPANTS: Eighty-five patients from rural WA participating. INTERVENTIONS:
Video consultation (VC) with a general ophthalmologist. MAIN OUTCOME MEASURES:
Number of referring practitioners and their locations, software and imaging
equipment used as well as the presentation, working diagnosis and follow-up plan
for each consultation. RESULTS: Eighty-five participants took part in a total of
100 VCs in the 5-month data collection period. There were 49 men (58%); age range
7-92 years; 31 identified as Indigenous Australian (37%). Participants were
referred by optometrists (59%), hospital district medical officers (23%) and GPs
(18%). Karratha (41%), Albany (20%) and Broome (14%) were the main VC locations.
There were 31 different eye conditions managed; red eye, acute vision loss, known
glaucoma and abnormal retinal photographs were the main presentations. Skype was
the commonly used software (71%). Images were provided in 63% of all VCs. The
main equipment used included digital retinal cameras (56%), smartphones (25%) and
digital slit lamps (13%). An outpatient appointment with the ophthalmologist was
recommended following 35 VCs. CONCLUSIONS: Optometrists used this service most
frequently, despite a lack of financial incentive. Digital retinal cameras and
smartphones were the most commonly used imaging modalities. Overall, real-time
teleophthalmology was used in the management of a broad range of eye conditions
and was a useful supplement to outreach ophthalmology services.
PMID- 25851960
TI - Use of narrow-diameter implants in the posterior jaw: a systematic review.
AB - STATEMENT OF PROBLEM: Evidence is limited on the efficacy of narrow-diameter
implants (NDIs) in the posterior jaw. PURPOSE: The purpose of this systematic
review was to assess the survival of NDIs and provide guidelines for their safe
use. MATERIALS AND METHODS: Electronic search of the English-language literature
enriched by hand search to identify suitable publications was made. Only peer
reviewed clinical studies published from January 1990 through March 2014 were
included. RESULTS: Seventeen studies with a total of 1644 implants met the
inclusion criteria, with an observation period from 1 up to 12 years. The mean
survival rate of 98.6% was reported. Technical and other complications were
observed. CONCLUSION: Short-term clinical data suggest that NDIs may serve in the
posterior jaw as an alternative to standard-diameter implants. However, certain
clinical conditions must be observed to assure long-term success.
PMID- 25851961
TI - Successful emergency combined therapy with partial splenic arterial embolization
and endoscopic injection therapy against a bleeding duodenal varix in a child.
AB - There is no consensus guidelines for treating duodenal variceal bleeding, which
is a rare and life-threatening complication of portal hypertension. Here we
report an exceedingly unusual case in a 9-year-old boy who had developed left
sided portal hypertension after surgical treatment for pancreatoblastoma followed
by a duodenal variceal bleeding with massive melena, severe anemia (hemoglobin
4.5 g/dL) and hypovolemic shock. Emergency partial splenic arterial embolization
(PSE) provided a reduction of variceal bleeding and improved blood pressure.
Endoscopic injection sclerotherapy (EIS) was subsequently performed and stopped
the duodenal variceal bleeding without the complication of portal vein thrombosis
caused by injected sclerosant under hepatopetal flow. Our case demonstrates that
emergency combined therapy with PSE and EIS can be considered as the therapeutic
option for the management of left-sided portal hypertension-induced ectopic
variceal bleedings in order to avoid the complication of portal embolization by
EIS and provide effective hematostasis.
PMID- 25851962
TI - Mechanism of DNA assembly as revealed by energy barriers.
AB - The mechanism of DNA assembly is revealed by analyzing the energy barriers during
nucleation and growth. The assembly is controlled by two competing parameters:
the conformation adjustment rate of DNA strands and the spreading rate of new
strands on the nuclei surface, both of which are temperature dependent and can be
tuned by sequence design.
PMID- 25851963
TI - An unusual presentation of erythema multiforme in a paediatric patient.
AB - BACKGROUND: Erythema multiforme (EM) is an acute, vesiculobullous disease of skin
and mucous membranes with symptoms ranging from mild to severe. A complex
interaction of different factors has been implicated the condition; the majority
with a preceding herpes simplex infection. This report describes an unusual
presentation of erythema multiforme affecting the lips and oral mucosa of a
healthy 7-year-old boy in the form of lip adherence. CASE REPORT: Two weeks
following eruption of oral ulcerations, a 7-year-old healthy boy developed severe
erosive ulceration of both lips, causing complete lip adherence. This was
accompanied by marked bilateral submandibular and cervical lymphadenopathy,
tremor and sweating. Clinical and laboratory investigations led to a diagnosis of
erythema multiforme. The patient was treated initially with gentle application of
Vaseline between the lips using cotton buds in an attempt to release lip
adhesion, followed by surgical release of the lips under general anaesthesia.
Analgesics and topical steroid mouthwash were provided. FOLLOW-UP: Seven months
later, the patient presented with a recurrence of his EM which included lesions
on the skin. The patient was treated with antivirals, topical and systematic
steroids to suppress the recurrent attacks of EM. Eighteen months following the
initial presentation the patient and parent reported considerable decrease in the
frequency, severity and duration of the occurrence of intra-oral ulcers, with no
major episode of target lesions on the skin. CONCLUSION: Erythema multiforme is
rare in children, however it should be considered in the differential diagnosis
of recurrent erosive oral ulcerative lesions especially when the oral lesions
resemble those of primary herpetic gingivostomatitis.
PMID- 25851964
TI - Maternal attitudes towards tooth decay in children aged 12-18 months in Pelotas,
Brazil.
AB - AIM: This was to assess mothers' attitudes towards dental caries in children aged
12-18 months. METHODS: This study targeted mothers of children aged 12-18 months.
Data about demographic and socioeconomic status were collected by interviews with
each mother. In addition, the mother was asked about her attitudes regarding
caries in her child's primary teeth. A dental examination of each child was also
conducted. Chi-square, bivariate, and multiple logistic regression analyses were
performed. RESULTS: A total of 262 mother-child pairs were included, and 18.7 %
of the children had dental caries. If a child presented with dental caries in
their primary teeth, 93.5 % of the mothers reported that they would take the
child to a dentist. Mothers who had only one child and those who had children
with dental caries were more likely to report that they did not expect primary
dental caries treatment by the dentist. CONCLUSION: Most mothers reported that
they would take their children to a dentist when they presented with dental
caries. Despite this positive result, educational measures should continue to be
emphasised, especially among mothers of children at a higher risk of caries and
among first-time mothers.
PMID- 25851966
TI - Older people living alone at home with terminal cancer.
AB - This study describes the lived experiences of older people coping with terminal
cancer and living alone, focusing on how they face challenges of the biographical
life changes from their disease progression. Face-to-face semi-structured
interviews were conducted in two phases with palliative care clients of a
community-based service in Western Australia (2009-2011): Brief interviews with
43 cancer patients who live alone and then in-depth interviews with 8 of them.
Using biographical disruption as the analytical framework for interpreting the
qualitative data, four main themes emerged: Biographical disruption: adjusting to
change; Biographical continuity: preserving normality; Biographical
reconstruction: redefining normality; and Biographical closure: facing the end.
Biographical disruption was a suitable framework for analysis, permitting
identification of the biographical disruptions of the individual's world and the
reframing that is undertaken by the individual to maintain autonomy and
independence while acknowledging and accepting their closeness to death.
Understanding the factors associated with the individual's need to maintain their
own identity will enable nurses working with this population to tailor support
plans that meet the individuals' needs while maintaining or restoring the
person's sense of self. Interventions that directly address end-of-life suffering
and bolster sense of dignity and personhood need to be considered.
PMID- 25851968
TI - [The pathogenesis of Ebola virus disease].
PMID- 25851967
TI - Evaluation of advanced multiplex short tandem repeat systems in pairwise kinship
analysis.
AB - The AmpFLSTR Identifiler Kit, comprising 15 autosomal short tandem repeat (STR)
loci, is commonly employed in forensic practice for calculating match
probabilities and parentage testing. The conventional system exhibits
insufficient estimation for kinship analysis such as sibship testing because of
shortness of examined loci. This study evaluated the power of the PowerPlex
Fusion System, GlobalFiler Kit, and PowerPlex 21 System, which comprise more than
20 autosomal STR loci, to estimate pairwise blood relatedness (i.e., parent
child, full siblings, second-degree relatives, and first cousins). The genotypes
of all 24 STR loci in 10,000 putative pedigrees were constructed by simulation.
The likelihood ratio for each locus was calculated from joint probabilities for
relatives and non-relatives. The combined likelihood ratio was calculated
according to the product rule. The addition of STR loci improved separation
between relatives and non-relatives. However, these systems were less effectively
extended to the inference for first cousins. In conclusion, these advanced
systems will be useful in forensic personal identification, especially in the
evaluation of full siblings and second-degree relatives. Moreover, the additional
loci may give rise to two major issues of more frequent mutational events and
several pairs of linked loci on the same chromosome.
PMID- 25851969
TI - [How to improve the diagnosis rate of early gastric cancer in China].
AB - China has great burden of gastric cancer, and the diagnosis rate of early gastric
cancer is relatively low (<10%). To perform screening, early endoscopic diagnosis
and treatment of gastric cancer in high-risk population is a feasible and
efficient way to change the current status. Therefore, the Chinese Society of
Digestive Endoscopy recently issued Consensus on screening, "Endoscopic diagnosis
and treatment of early gastric cancer screening in China". The consensus suggests
a feasible and efficient strategy for early detection of gastric cancer:
screening with non-invasive procedures, followed by intensive endoscopic
examination for screened high-risk population. In this article, we also describe
the current status, the causes, high-risk population and early diagnosis of
gastric cancer in China; and review the new development of serology and
endoscopic techniques for early diagnosis.
PMID- 25851970
TI - [Efficacy of epigallocatechin gallate in treatment of alkali burn injury of
murine cornea].
AB - OBJECTIVE: To evaluate the efficacy of epigallocatechin gallate (EGCG) in
treatment of corneal alkali burn injury in mice. METHODS: Corneal alkali burn
injury was induced by sodium hydroxide method in C57BL/6J mice. The mice with
cornea burns were treated intraperitoneally with EGCG solution or phosphate
buffer solution (PBS) respectively. The healing of corneal epithelium, the
formation of corneal neovascularization (CNV) and the inflammation reaction were
assessed by slit -lamp microscopy and histological examination. Expression of
vascular endothelial growth factor (VEGF) mRNA and protein in cornea was
evaluated by real -time reverse transcription polymerase chain reaction (RT-PCR)
and immunohistochemistry, respectively. Myeloperoxidase (MPO) assay was used to
quantitatively evaluate the polymorphonuclear neutrophils (PMNs) infiltration in
the corneas. RESULTS: The healing rate of corneal epithelium in EGCG group was
significantly higher than that of PBS group at d1, d3 and d7 after treatment (d1:
41.0%+/-13.0% vs 23.8%+/-7.6%; d3: 76.6%+/-7.5% vs 61.2%+/-6.8%; d7: 87.8%+/-8.5%
vs 74.0%+/-9.1%; all P <0.05). The CNV scores and the number of CNV in the
corneal sections of EGCG group were significantly lower than those of PBS group
at d3, d7 and d14 after treatment (CNV score: d3: 1.1+/-0.5 vs 6.6+/-1.0; d7:
1.3+/-0. 3 vs 8.1+/-1.0; d14: 0.9+/-0.2 vs 9.2+/-1.1; CNV number: d3: 1.68+/-0.61
vs 2.92+/-0.95; d7: 4.80+/-1.36 vs 7.92+/-1.28; d14: 3.64+/-0.71 vs 5.88+/-0.76;
all P<0.05) . The expression of VEGF protein at d3 (0.19+/-0.05 vs 0.45+/-0.08)
and d7 (0.42+/-0.07 vs 0.84+/-0.09), the expression of VEGF mRNA at d1, d3 and d7
in EGCG group were significantly lower than those in PBS group (all P <0.05).
Compared to PBS group, the inflammatory index at d3 (3.2+/-0.4 vs 3.7+/-0.5) and
d7 (2.3+/-0.5 vs 4.0+/-0.0), the number of PMNs in the corneal sections and the
MPO values at d3, d7 and d14 in EGCG group were significantly decreased (PMNs:
d3: 34.5+/-15.7 vs 90.0+/-28.8; d7: 17.1+/-11.4 vs 54.9+/-25.9; d14: 12. 8+/-4.6
vs 39.0+/-17.9; all P <0.05). CONCLUSION: In the murine corneal alkali burn
model, intraperitoneal injection of EGCG solution can promote the healing of
corneal epithelium, inhibit the formation of CNV and reduce the inflammatory cell
infiltration in the corneas.
PMID- 25851971
TI - [Protective effect of grape seed proanthocyanidin on cultured RGC-5 cells against
CoCl2-induced hypoxic injury].
AB - OBJECTIVE: To investigate the protective effects of grape seed proanthocyanidin
extracts (GSPE) against CoCl2-induced hypoxic injury in cultured RGC-5 cells.
METHODS: CoCl2(400 MUmol/L) was used to induce hypoxic injury in cultured RGC-5
cells; the cells were pretreated with 0,100,200,400 and 800MUmol/L GSPE for 24h.
The cell viability was assayed by MTT; the apoptosis was detected by Hoechst
33342 staining; the intracellular reactive oxygen species (ROS) was measured by
H2DCFDA oxidative reaction. The mRNA expression of Bcl-2, caspase 9 and caspase 3
was determined by real-time PCR. RESULTS: Compared to hypoxic control group,
pretreatment with GSPE significantly increased viability of RGC-5 cells
(P<0.001), reduced cell apoptosis (P<0 .001) and intracellular ROS(P <0 .001). In
addition, GSPE significantly increased the mRNA expression of Bcl-2(P<0 .001) and
decreased mRNA expression of caspase 9(P<0 .001) and caspase 3(P<0 .001) compared
to hypoxic control group. CONCLUSION: GSPE may have a protective effect against
CoCl2-induced hypoxic injury in cultured RGC-5 cells. The decrease of
intercellular ROS, up-regulation of Bcl-2 and down-regulation of caspase 9 and
caspase 3 may be involved in the mechanism of the protective effect of GSPE.
PMID- 25851972
TI - [Neuroprotective effects of paeonol in a cell model of Parkinson disease].
AB - OBJECTIVE: To investigate the effects of paeonol on neuron cell model of
Parkinson disease (PD). METHODS: The cell model of Parkinson disease was induced
by treatment of 1-Methyl-4-phenylpyridinium (MPP+) in PC12 cells, the PD model
cells were treated with 1 MUmol/L, 3 MUmol/L or 9 MUmol/L paeonol for 24h,
respectively. Cell viability and LDH leakage were detected by MTT and lactate
dehydrogenase (LDH) assay; the apoptosis of PC12 cells was assessed by Hoechst
33258 staining and flow cytometry; reactive oxygen species (ROS) production was
detected by DCFH-DA method; and the ratio of Bax/Bcl-2 and activation of caspase
3 were determined by Western blotting. RESULTS: MPP+ treatment significantly
reduced cell viability, increased LDH leakage, enhanced the proportion of
apoptotic cells and ROS production. In addition, MPP+ treatment dramatically
increased the Bax/Bcl-2 ratio, and the activation of caspase-3. Compared to PD
model group, paeonol treatment significantly enhanced cell viability, decreased
LDH leakage, inhibited the proportion of apoptotic cells and ROS production,
reduced the Bax/Bcl-2 ratio and the activated caspase-3 protein. CONCLUSION:
Paeonol can prevent PC12 cells from apoptosis induced by MPP+, and the mechanism
may be associated with the down-regulation of ROS production, Bax/Bcl-2 ratio and
Caspase-3 activation.
PMID- 25851973
TI - [Effect of licorice flavonoids on kainic acid-induced seizure in mice].
AB - OBJECTIVE: To investigate the effect of licorice flavonoid (LF) on kainic acid
(KA)-induced seizure in mice and its mechanism. METHODS: Male adult ICR mice were
injected with 25 mg/kg KA to induce temporal lobe seizure. LF was administrated 7
d before seizure induction (pre-treatment) or 24 h after seizure induction (post
treatment) for 7 d. Acute seizure latency, seizure stage and duration were
observed and compared between LF- and vehicle-treated mice. From d2 on, mice with
status epilepticus were video-monitored for spontaneous seizures, 10 h/d for 6 w.
Immunohistochemical analysis of BrdU and Timm staining was conducted to detect
the neurogenesis and mossy fiber sprouting, respectively. RESULTS: No significant
difference was observed in acute seizure latency, seizure stage and duration
between LF-and vehicle-treated mice. KA-induced acute seizure resulted in
spontaneous seizure in mice, and the seizure frequency was increased with time.
Pre- and post-treatment with LF decreased seizure frequency from w3 after
modeling [(0.58+/-0.15)/d, (0.38+/-0.38)/d vs (1.23+/-0.23)/d, P <0.05].
Furthermore, KA-induced seizure resulted in robust neurogenesis and mossy fiber
sprouting, while treatment with LF both pre- and post- KA injection significantly
inhibited neurogenesis (15.6+/-2.6, 17.1+/-3.1 vs 28.9+/-3.5, P <0.05) and mossy
fiber sprouting (1.33+/-0.31, 1.56+/-0.42 vs 3.0+/-0.37, P <0.05). CONCLUSION: LF
has no significant anti-seizure effect. However, it can decrease epileptogenesis
through inhibition of neurogenesis and mossy fiber sprouting.
PMID- 25851974
TI - [Treatment of rheumatoid arthritis with flavonoids of Echinps latifolius Tausch
in rat model].
AB - OBJECTIVE: To investigate the effect of Flavonoids extracted from Echinps
latifolius Tausch(FELT) on rheumatoid arthritis (RA) in rat model. METHOD: Fifty
SD rats were randomly divided into model group, control group, and low, medium,
and high-dose FELT groups (n=10 in each group). Complete Freund's adjuvant (0.1
mL) was used to induce RA in rats. FELT in doses of 50 mg/kg, 100 mg/kg, 150
mg/kg was given to rats in low, medium and high-dose FELT groups by gavage, and
same volume of PBS was given to rats in control group. The arthritis score and
the paw swelling score were measured to evaluate the therapeutic effect of FELT.
Real time qPCR was used to detect the mRNA expression of fibronectin and MMP3 in
synovial tissue and the mRNA expression of caspase 3, Bcl-2 and Bcl-2 associated
X protein (Bax) in fibroblast-like synoviocytes (FLS). RESULTS: The arthritis
score and the paw swelling score were significantly decreased in three FELT
groups compared to RA model rats (P <0.05). The relative expression levels of FN
and MMP3 mRNA in synovium of three FELT-treatment groups were significantly lower
than those in model group (1.80, 1.76 and 1.67 vs 2.53; 1.69, 1.46 and 1.45 vs
2.67, respectively, all P <0.05). The relative expression levels of Bax and
caspase 3 mRNA in FLSs of three FELT groups were higher than those in model group
(0.56, 0.58 and 0.60 vs 0.30; 0.54, 0.56 and 0.59 vs 0.29, respectively, all P
<0.05); while the relative expression levels of Bcl-2 mRNA in FELT groups were
lower than that in model group (2.20, 2.08 and 2.08 vs 4.04, respectively, P
<0.05). CONCLUSION: FELT may inhibit the synovium proliferation in RA model rats
through promoting the FLS apoptosis.
PMID- 25851975
TI - [Hypouricemic effect of ethanol extracts from Dioscoreae Nipponicae Rhizoma].
AB - OBJECTIVE: To investigate the effect of ethanol extracts from Dioscoreae
Nipponicae Rhizoma on hyperuricemic mice. METHODS: The hyperuricemia was induced
by gavage of hypoxanthine and subcutaneous injection of potassium oxonate (model
A) or subcutaneous injection of uric acid (model B) in ICR male mice. The mice in
ethanol extracts groups were administrated with Dioscoreae Nipponicae Rhizoma
ethanol extracts 5.4 g/kg by gavage, the positive control groups were given with
10 mg/ml allopurinol or 5 mg/ml benzbromarone by gavage, respectively. The plasma
uric acid levels were measured by using HPLC. RESULTS: The plasma uric acid
levels of model group, control group and ethanol extract group in model A mice
were (40.03+/-27.24), (4.08+/-1.47) and (18.10+/-8.87) g/mL (compared with model
group, P <0.05), respectively. The plasma uric acid levels of model group,
control group and ethanol extract group in model B mice were (18.57+/-3.83),
(4.29+/-2.36) and (15.36+/-2.71) g/mL (compared with model group, P <0.05),
respectively. CONCLUSION: The ethanol extracts from Dioscoreae Nipponicae Rhizoma
have certain hypouricemic effect in hyperuricemic mice induced by hypoxanthine
and potassium oxonate or by uric acid.
PMID- 25851976
TI - [Factors related to therapeutic outcomes of intravenous thrombolysis in stroke
patients with different severity].
AB - OBJECTIVE: To investigate the factors related to therapeutic outcomes of
intravenous thrombolysis in patients with acute ischemic stroke (AIS) of
different severity. METHODS: Clinical data of patients with AIS treated with
intravenous thrombolysis in the Second Affiliated Hospital, Zhejiang University
School of Medicine between June 2009 and December 2013 were retrospectively
reviewed. According to National Institutes of Health Stroke Scale (NIHSS),
patients were categorized as mild stroke (<=8, n=134), moderate stroke (9-15,
n=121) and severe stroke(>=16, n=110). The good outcome was defined as modified
Rankin Scale <= 2. The factors related to functional outcomes and hemorrhagic
transformation (HT) were analyzed and compared among 3 groups. RESULTS: Among 365
enrolled patients, good outcomes in 3 groups were 78.4% (105/134), 47.9% (58/121)
and 24.5%(27/110), respectively. In patients with mild stroke, age (OR=0.937,
95%CI: 0.898-0.978; P=0.003), baseline NIHSS (OR=0.732, 95%CI:0.564-0.950;
P=0.019), onset to needle time (ONT) within 270 min (OR=4.109, 95%CI:1.441
11.719; P=0.008) independently predicted good outcome, while baseline glucose
(OR=1.326, 95%CI:1.009-1.743; P=0.043) was independently associated with
parenchymal hematoma (PH). In patients with moderate stroke, age (OR=0.954,
95%CI: 0.924-0.984; P=0.003) and baseline NIHSS (OR=0.760, 95%CI: 0.619-0.933;
P=0.009) independently predicted good outcome, while atrial fibrillation
(OR=3.307, 95%CI: 1.140~9.596; P=0.028) and systolic pressure (OR=0.967, 95%CI:
0.943~0.991; P=0.008) was independently associated with hemorrhagic infaction.
Atrial fibrillation (OR=36.972, 95%CI: 1.770-772.462; P=0.02) was independently
associated with PH. In patients with severe stroke, baseline NIHSS (OR=0.808,
95%CI:0.677-0.963; P=0.018) independently predicted good outcome, while no
independent risk factors of HT was found. CONCLUSION: For different severity of
AIS patients, the related factors of functional outcome and HT after thrombolysis
were different.
PMID- 25851977
TI - [Nutritional status in acute stage ischemic stroke and its relation to disease
severity and prognosis of patients].
AB - OBJECTIVE: To investigate the nutritional status in acute stage ischemic stroke
and its relation to disease severity and prognosis of patients. METHODS: Fifty
patients with ischemic stroke were admitted in hospital within 48 h after onset.
National Institute of Health stroke scale (NIHSS) was used to assess the severity
of stroke. Physical index and laboratory index were measured on d1, d7 and d14
after admission. Physical index included body weight, body mass index, triceps
skin folds, upper arm circumference and arm muscle circumference. Laboratory
index included prealbumin, high sensitivity C-reactive protein (hs-CRP),
complement C3 and cortisol. The severity of metabolic disturbance was expressed
as the difference of biochemical indexes between the d7 and d1. All cases were
followed up for 6 months. The prognosis of stroke was evaluated with modified
Rankin (mRankin) scores. RESULTS: No significant changes of physical indexes were
found between d7 and d1. The levels of prealbumin and complement C3 on d7 after
admission were significantly decreased compared to d1 (198.8 mg/L+/-20.3 mg/L vs
286.7 mg/L+/-23.8 mg/L and 0.6 g/L+/-0.1 g/L vs 1.0 g/L+/-0.1 g/L, respectively,
both P<0.05). The levels of hs-CRP and cortisol at d7 were significantly
increased compared to d1 (495.2 nmol/L+/-39.5 nmol/L vs 24.1 mg/L+/-5.2 mg/L and
396.4 nmol/L+/-41.3 nmol/L vs 5.1 mg/L+/-1.2 mg/L, respectively, both P<0.05). On
d14 after admission hs-CRP (13.2 mg/L+/-4.5 mg/L) and cortisol levels (463.4
nmol/L+/-32.1 nmol/L) were still significantly higher than d1 (both P<0.05).
However, there were no difference in prealbumin (259.2 mg/L+/-22.8 mg/L) and
complement C3 (0.8 g/L+/-0.2 g/L) levels between d1 and d14 after admission.
Correlation analysis revealed that the NIHSS scores and mRankin scores were
correlated with nutrition metabolism disturbances (P<0.05). CONCLUSION: Nutrition
metabolism disturbances in patients with acute ischemic stroke are related to the
disease duration, the severity and prognosis of stroke.
PMID- 25851978
TI - [Inhibition of gap junctional intercellular communication protects astrocytes
from hypoxia/reoxygenation injury].
AB - OBJECTIVE: To investigate the effects of inhibiting gap junctional intercellular
communication on hypoxia/reoxygenation injury in astrocytes. METHODS: Primary
cultured cerebral cortical astrocytes of neonate rats were divided into normal
control group, hypoxia reoxygenation injury group and 18-alpha-glycyrrhetinic
acid and oleamide (gap junctional intercellular channel inhibitors) group. The
gap junction intercellular communication was determined by Parachute assay. The
viability of astrocyes was detected by MTT assay. The apoptosis of astrocytes
were detected with annexin V/PI and Hoechst 33258 staining. RESULTS: Compared
with the normal control group, the gap junctional function of astrocytes was
increased significantly in ischemia/reperfusion group (P<0.01), the surviving
fraction of astrocytes decreased significantly (P<0.01) and its cell apoptosis
ratio increased significantly (P<0.01). Compared with the ischemia/reperfusion
group, the gap junctional function of astrocytes in18-alpha-glycyrrhetinic acid
and oleamide group decreased significantly (P<0.01), the viability of astrocytes
increased significantly (P<0.01), while cell apoptosis decreased significantly
(P<0.01). CONCLUSION: Inhibition of intercellular gap junction has protective
effect against hypoxia/reoxygenation injury in astrocytes.
PMID- 25851979
TI - [Laparoscopic anti-reflux surgery with biological mesh in treatment of
gastroesophageal reflux disease].
AB - OBJECTIVE: To evaluate the application of biological mesh in laparoscopic anti
reflux procedure for gastroesophageal reflux disease (GERD). METHODS: The
clinical data of 20 consecutive GERD patients underwent anti-reflux surgery in
Sir Run Run Shaw Hospital from December 2012 to April 2014 were retrospectively
analyzed. The laparoscopic hiatal repair with 360 fundoplicaiton was performed
and the biological mesh (BiodesignTM, Surgsis) was implanted for reinforcement of
hiatal repair. RESULTS: All laparoscopic procedures were successful, no
conversion and no intra-operative complications occurred. The pre-operative
complains were relieved in all patients, and no recurrence was observed during 3
18 month of follow-up. Six patients got dysphagia after operation; 5 of them were
controlled through medication and psychological induction; 1 received esophageal
dilatation by bougie. CONCLUSION: The application of biological mesh in
laparoscopic anti-reflux procedure for gastroesophageal reflux disease is
satisfactory.
PMID- 25851980
TI - [Single-incision laparoscopic surgery with self-made port for totally
extraperitoneal hernioplasty: a report of 7 cases].
AB - OBJECTIVE: To explore the feasibility of single-incision laparoscopic totally
extraperitoneal hernioplasty (SILS-TEP) with self-made port for repairing of
inguinal hernia. METHODS: SILS-TEP was performed in 7 inguinal hernia patients (9
sides) with conventional laparoscopic instruments and self-made port, which
composed of a wound retractor, surgical gloves and 3 ordinary trocars. The
clinical data and follow-up results of 7 cases were retrospectively collected and
analyzed. RESULTS: The self-made port was applied for SILS-TEP uneventfully
without the need of additional ports in all 7 patients (9 inguinal hernias). The
median operating time was 90. 0 (70-125) min, intraoperative blood loss was 10. 0
(5. 0-20. 0) mL and postoperative hospital stay was 2.0 (2. 0-4. 0) d. The median
pain scores of visual analog scale (VAS) at 6 h,12 h, 24 h and 14 d were 3(2~4),
2(1~2), 1(0~2) and 0(0~1), respectively. There were no intraoperative
complications reported, and all patients were satisfied with wound healing. No
hernia recurrence was observed during the 3-months of follow-up. CONCLUSION: Our
initial experiences show that SILS-TEP with self-made port is a safe and feasible
surgery, which can simplify the procedure with available equipments and reduce
the cost, therefore can be applied in grass-root hospitals.
PMID- 25851981
TI - [Correlation between follicle-stimulating hormone and total procollagen I N
terminal propeptide in perimenopausal women].
AB - OBJECTIVE: To investigate the correlation between serum levels of follicle
stimulating hormone (FSH) and total procollagen I N-terminal propeptide (TP1NP)
in perimenopausal women. METHODS: Total 274 women aged 33~60 y with
perimenopausal period were enrolled in this study. Serum levels of FSH and TP1NP
were detected by electrochemiluminescence. RESULTS: In 274 perimenopausal women,
the average level of TP1NP was (48.99+/-20.31) ng/mL, which was positively
correlated with FSH level (r=0.159, P=0.009). In 40-50 age group, TP1NP level in
women with FSH<40 mIU/mL was lower than that in those with FSH>=40mIU/mL
[(35.05+/-18.11) ng/mL vs (51.33+/-24.67) ng/mL; t=-2.954, P=0.004]. However, in
<40 and 50-60 age groups, there were no significant differences in TP1NP levels
between patients with FSH<40 mIU/mL and those with FSH>=40 mIU/mL (t=-0.063,
P=0.950; t=1.177, P=0.242). Multiple linear regression analysis showed that
standardized coefficients of age variable was 0.047 (P=0.448) and standardized
coefficients of FSH variable was 0.146 (P=0.019). CONCLUSION: TP1NP levels showed
a certain correlation with FSH in perimenopausal women, especially for women aged
40-50, indicating that high FSH levels may be important factors for osteoporosis
in postmenopausal women.
PMID- 25851982
TI - [Effect of occlusal reconstruction on cerebral blood flow and cerebral oxygen
saturation in patients with malocclusion].
AB - OBJECTIVE: To investigate the effect of occlusal reconstruction on blood flow
velocity and cerebral oxygen saturation in patients with malocclusion. METHODS:
Thirty-three patients with malocclusion treated with occlusal reconstruction in
Department of Stomatology, Medical School of Huzhou Normal College from Feb 2011
to Oct 2013 were enrolled in the study. The systolic peak flow velocity (vs), end
diastolic peak flow (vd) , mean peak flow velocity (vm) of middle cerebral artery
and the oxygen saturation (rScO2) in the brain were detected at rest or chewing
status by using transcranial Doppler color ultrasonography and near-infrared
spectroscopy, respectively. RESULTS: In rest state, vm was significantly
increased on 3 months after treatment, while vs and vd were significantly
increased on 6 months after treatment and rScO2 were increased on 12 months after
treatment (P<0.05). In chewing state, vs, vm, and rScO2 were increased on 3
months after treatment, and vd was increased on 6 months after treatment
(P<0.05). CONCLUSION: Occlusal reconstruction can increase blood flow velocity of
middle cerebral artery and cerebral oxygen saturation and improve oxygen supply
of the brain in patients with malocclusion.
PMID- 25851983
TI - [Progress on matrix metalloproteinase in axonal regeneration].
AB - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases. MMPs can
degrade and remodel extracellular matrix, also active or inactive many molecules
attaching to matrix including receptors, growth factors and cytokines, so that
injury-induced MMPs can change the extracellular environment to affect the axonal
regeneration in central nervous system. In this review, with spinal cord injury
(SCI) as an example we discuss the effects of MMPs on inflammation, neuronal
viability, extracellular molecules, glial scar and axonal remyelination, which
are all important to axonal regeneration.
PMID- 25851984
TI - [Progress on association between low-density lipoprotein receptor and metabolic
syndrome].
AB - Low-density lipoprotein receptor (LDLR) and metabolic syndrome (MS) are closely
correlated. Changes in LDLR expression, feedback regulation and degradation,
impacts of LDLR deficiency on blood lipid levels, roles of LDLR in islet beta
cell dysfunction and cholesterol homeostasis dysregulation, expression of LDLR
gene nuclear transcription factors and polymorphism of LDLR gene segments are all
involved in the development of specific components of MS. In recent years, a
variety of targets and intervention mechanisms in relation to LDLR and MS have
been extensively studied. Knowledge about association between LDLR and MS may
contribute to the development of strategies for prevention and treatment of MS.
This article reviews the update on the association between LDLR and MS.
PMID- 25851985
TI - [Bioelectric-technology in tumor minimally invasive therapy--from the 11th
International Bioelectrics Symposium].
PMID- 25851986
TI - [Highlights of the 19th congress of Asia-Pacific Blood and Marrow
Transplantation].
PMID- 25851987
TI - Engineered microstructure granules for tailored drug release rate.
AB - Biomaterials developed for controlled drug delivery have demonstrated excellent
results in the present study. A biomaterial prepared using hydroxyapatite (HAp)
was shown to have a hollow structure with the presence of interconnected pores to
house drug carriers. The poly(lactic-co-glycolic acid) particles were used as
drug carriers loaded with dexamethasone, a corticosteroid that is known to
promote osteoinduction. The surface of the drug carriers was modified using
polyethyleneimine, and then conjugated to the surface of HAp granules. The hollow
HAp granules had drug carriers on both their inner and outer surfaces and showed
a controlled drug release rate that was comparable to that of granules containing
drug carriers on their outer surface alone. The pores were designed for insertion
of drug carriers and preosteoblasts. Consequently, the biomaterials influenced
cellular behavior by first promoting cell proliferation and then inducing early
stage osteogenic differentiation. The effects of controlled release rate were
evidenced for up to two weeks after cell seeding, resulting in an increase of
osteogenic differentiation. In summary, drug carriers loaded onto hollow HAp
granules were shown to be suitable for patients who require replacement of
missing bone for repair of bone fractures that are extremely complex, pose a
significant health risk to the patient, or fail to heal properly.
PMID- 25851990
TI - Embolic stroke associated with intra-carotid injection of buprenorphine.
PMID- 25851993
TI - Diagnosis of allergy against beta-lactams in primary care: prevalence and
diagnostic criteria.
AB - BACKGROUND: Secondary care studies showed that a recorded allergy to beta-lactams
could not be confirmed by valid allergy testing in >85% of cases. In daily
practice, recorded beta-lactam allergies probably cause prescription of secondary
choice antibiotics. This overrating of beta-lactam allergy hampers appropriate
use of narrow spectrum antibiotic and generates unnecessary cost and bacterial
resistance. OBJECTIVE: To assess registration and over diagnosis of allergies
against beta-lactams in Dutch primary care. METHODS: A retrospective cohort study
in 8288 primary care subjects was performed. Patients with recorded allergy were
identified through International Classification for Primary Care coding. Signs
and symptoms of the recorded allergic reaction and patient's characteristics were
extracted from patient's files and patients were sent a questionnaire. The
probability of allergy was based on a composite reference standard that was
scored by two authors independently. RESULTS: One hundred sixty-three subjects
had a recorded allergy (2.0%). In 51.5% of cases, no characteristics of the
recorded allergic reaction were reported in patients' medical files. Based on our
composite reference standard, allergy was excluded in 19 subjects (11.7%). Risk
factors for allergy registration were female gender, age <4 years, and the
comorbidities-asthma, allergies and skin disorders. CONCLUSIONS: The prevalence
of recorded allergy against beta-lactam antibiotics in a large Dutch primary care
centre was 2%. Due to lack of registration of accompanying signs and symptoms of
the recorded allergy, this diagnosis is uncertain in most patients. Better
documentation and classification by a screening algorithm of future possible
allergic reactions to beta-lactams are needed in primary care.
PMID- 25851992
TI - Testing the waters: Ethical considerations for including PrEP in a phase IIb HIV
vaccine efficacy trial.
AB - BACKGROUND: The field of HIV prevention research has recently experienced some
mixed results in efficacy trials of pre-exposure prophylaxis, vaginal
microbicides, and HIV vaccines. While there have been positive trial results in
some studies, in the near term, no single method will be sufficient to quell the
epidemic. Improved HIV prevention methods, choices among methods, and coverage
for all at-risk populations will be needed. The emergence of partially effective
prevention methods that are not uniformly available raises complex ethical and
scientific questions regarding the design of ongoing prevention trials. METHODS:
We present here an ethical analysis regarding inclusion of pre-exposure
prophylaxis in an ongoing phase IIb vaccine efficacy trial, HVTN 505. This is the
first large vaccine efficacy trial to address the issue of pre-exposure
prophylaxis, and the decisions made by the protocol team were informed by
extensive stakeholder consultations. The key ethical concerns are analyzed here,
and the process of stakeholder engagement and decision-making described.
DISCUSSION: This discussion and analysis will be useful as current and future
research teams grapple with ethical and scientific study design questions
emerging with the rapidly expanding evidence base for HIV prevention.
PMID- 25851994
TI - MiR-107 down-regulates SIAH1 expression in human breast cancer cells and
silencing of miR-107 inhibits tumor growth in a nude mouse model of triple
negative breast cancer.
AB - We have reported that SIAH1 is down-regulated and associated with apoptosis and
invasion in human breast cancer. However, the molecular mechanisms leading to
SIAH1 down-regulation remain to be elucidated. Here, we demonstrated that miR-107
directly down-regulates SIAH1 expression in human breast cancer cells. Over-
expression of miR-107 reduced SIAH1 expression, promoted human breast cancer cell
proliferation, colony formation, migration and invasion, and inhibited apoptosis.
On the contrary, silencing of miR-107 increased SIAH1 expression and inhibited
the tumor growth of MDA-MB-231 cells, a kind of triple-negative breast cancer
(TNBC) cells, in vitro and in vivo. Our results reveal that miR-107 is an
upstream regulator for SIAH1 down-regulation in human breast cancer cells and miR
107 provides a potential effective target for the treatment of TNBC.
PMID- 25851995
TI - Response to hydroxyurea among Kuwaiti patients with sickle cell disease and
elevated baseline HbF levels.
PMID- 25851996
TI - [Use of cold and cough medications prescribed in Primary Care clinics for
children less than 14 years].
AB - OBJECTIVE: To evaluate cold and cough medications and their suitability in
children in Primary Health Care in Area V of the Asturian Health Service.
MATERIAL AND METHODS: A cross-sectional, descriptive and retrospective study was
conducted in which an analysis was performed of the respiratory diseases and the
prescriptions of 6 Primary Health Care paediatricians who worked in Area V of the
Asturian Health Service in 2011. An evaluation was made on the suitability of
these medications. An analysis was also made of the drug datasheet and clinical
recommendations (clinical guidelines, protocols or reports). RESULTS: A total of
424 cold and cough drugs: 249 antitussives, 155 mucolytics, and 20 "others" were
analyzed. The mean age was 5 years old. There was a total of 85.1% unsuitable
prescriptions. Off-label drugs were used in 11.6%. The prescribing was considered
unsuitable in 82.8% of prescriptions associated with R74, and 73% of R05. All of
the prescription drugs in children under 6 years old were unsuitable.
Mucolytics/"others" were not suitable in 99.4%, nor antitussives in 75.1%.
CONCLUSIONS: There is a high level of cold and cough drugs being prescribed in
children, with 85% of these being unsuitable. Children should only receive drugs
with a good risk and benefit ratio. Pediatricians should try to improve the
information about pediatric drug use and spread this information to parents,
doctors and nurses.
PMID- 25851997
TI - Solitary orange-yellow scalp lesion.
PMID- 25851999
TI - Multifunctional MgO Layer in Perovskite Solar Cells.
AB - A multifunctional magnesium oxide (MgO) layer was successfully introduced into
perovskite solar cells (PSCs) to enhance their performance. MgO was coated onto
the surface of mesoporous TiO(2) by the decomposition of magnesium acetate and,
therefore, could block contact between the perovskite and TiO(2). X-ray
photoelectron spectroscopy and infrared spectroscopy showed that the amount of
H(2)O/hydroxyl absorbed on the TiO(2) decreased after MgO modification. The
UV/Vis absorption spectra of the perovskite with MgO modification revealed an
enhanced photoelectric performance compared with that of unmodified perovskite
after UV illumination. In addition to the photocurrent, the photovoltage and fill
factor also showed an enhancement after modification, which resulted in an
increase in the overall efficiency of the cell from 9.6 to 13.9 %.
Electrochemical impedance spectroscopy (EIS) confirmed that MgO acts as an
insulating layer to reduce charge recombination.
PMID- 25851998
TI - A germline MTOR mutation in Aboriginal Australian siblings with intellectual
disability, dysmorphism, macrocephaly, and small thoraces.
AB - We report on three Aboriginal Australian siblings with a unique phenotype which
overlaps with known megalencephaly syndromes and RASopathies, including Costello
syndrome. A gain-of-function mutation in MTOR was identified and represents the
first reported human condition due to a germline, familial MTOR mutation. We
describe the findings in this family to highlight that (i) the path to
determination of pathogenicity was confounded by the lack of genomic reference
data for Australian Aboriginals and that (ii) the disease biology, functional
analyses in this family, and studies on the tuberous sclerosis complex support
consideration of an mTOR inhibitor as a therapeutic agent.
PMID- 25852000
TI - A Synthetic Route to Chiral Dihydrobenzothiazines through Ring Opening of
Activated Aziridines with 2-Halothiophenols/Copper-Powder-Mediated C-N
Cyclization.
AB - A simple protocol for the synthesis of dihydrobenzothiazines through regio- and
stereoselective S(N)2-type ring opening of N-tosylaziridines with sulfur
nucleophiles followed by copper-powder-mediated intramolecular C-N cyclization in
excellent yields (up to 95%) with high diastereo- and enantioselectivity (up to
>99%) is reported.
PMID- 25852001
TI - Mitochondrial oxidative stress mediates high-phosphate-induced secretory defects
and apoptosis in insulin-secreting cells.
AB - Inorganic phosphate (Pi) plays an important role in cell signaling and energy
metabolism. In insulin-releasing cells, Pi transport into mitochondria is
essential for the generation of ATP, a signaling factor in metabolism-secretion
coupling. Elevated Pi concentrations, however, can have toxic effects in various
cell types. The underlying molecular mechanisms are poorly understood. Here, we
have investigated the effect of Pi on secretory function and apoptosis in INS-1E
clonal beta-cells and rat pancreatic islets. Elevated extracellular Pi (1~5 mM)
increased the mitochondrial membrane potential (DeltaPsim), superoxide
generation, caspase activation, and cell death. Depolarization of the DeltaPsim
abolished Pi-induced superoxide generation. Butylmalonate, a nonselective blocker
of mitochondrial phosphate transporters, prevented DeltaPsim hyperpolarization,
superoxide generation, and cytotoxicity caused by Pi. High Pi also promoted the
opening of the mitochondrial permeability transition (PT) pore, leading to
apoptosis, which was also prevented by butylmalonate. The mitochondrial
antioxidants mitoTEMPO or MnTBAP prevented Pi-triggered PT pore opening and
cytotoxicity. Elevated extracellular Pi diminished ATP synthesis, cytosolic
Ca(2+) oscillations, and insulin content and secretion in INS-1E cells as well as
in dispersed islet cells. These parameters were restored following preincubation
with mitochondrial antioxidants. This treatment also prevented high-Pi-induced
phosphorylation of ER stress proteins. We propose that elevated extracellular Pi
causes mitochondrial oxidative stress linked to mitochondrial hyperpolarization.
Such stress results in reduced insulin content and defective insulin secretion
and cytotoxicity. Our data explain the decreased insulin content and secretion
observed under hyperphosphatemic states.
PMID- 25852002
TI - Lipid-induced insulin resistance does not impair insulin access to skeletal
muscle.
AB - Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal
muscle. Previously, we have shown that experimental insulin resistance induced by
lipid infusion prevents the dispersion of insulin through the muscle, and we
hypothesized that this would lead to an impairment of insulin moving from the
plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized
canine model and measured the appearance of insulin in the lymph as a means to
sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions.
Although lipid infusion lowered the glucose infusion rate and induced both
peripheral and hepatic insulin resistance, we were unable to detect an impairment
of insulin access to the lymph. Interestingly, despite a significant, 10-fold
increase in plasma FFA, we detected little to no increase in free fatty acids or
triglycerides in the lymph after lipid infusion. Thus, we conclude that
experimental insulin resistance induced by lipid infusion does not reduce insulin
access to skeletal muscle under clamp conditions. This would suggest that the
peripheral insulin resistance is likely due to reduced cellular sensitivity to
insulin in this model, and yet we did not detect a change in the tissue
microenvironment that could contribute to cellular insulin resistance.
PMID- 25852004
TI - Positive long-term outcomes from presuckling calcium supplementation in lactating
rats and the offspring.
AB - Adequate dietary calcium intake and the enhanced intestinal calcium absorption in
lactating mothers have long been postulated to prevent maternal bone loss and
benefit neonatal bone growth. We recently showed that calcium supplementation
just before breastfeeding efficiently alleviated lactation-induced bone loss in
dams as well as increased milk calcium concentration, which led to higher bone
mineral density (BMD) in the newborns. Herein, we further elaborated in detail
how presuckling calcium supplements worked in lactating rats and how they
benefited bone growth in the offspring. As revealed by bone histomorphometry,
presuckling supplement with calcium alone reduced the osteoclast surface and
active erosion surface, leading to an increase in trabecular thickness without
changes in trabecular separation or number in dams. The beneficial effects of
presuckling calcium supplements, particularly the regimen containing glucose and
galactose that enhanced intestinal calcium absorption, were found to last for 3
mo postweaning, although it could not restore estrogen-deficient osteopenia
induced by ovariectomy. Regarding the neonatal benefits, pups nursed by calcium
supplemented dams exhibited increases in trabecular BMD, which could be observed
even at the age of 27 wk. Bone elongation was also greater in pups of calcium
supplemented dams, which was due possibly to accelerated growth plate chondrocyte
turnover. It could be concluded that calcium supplements markedly diminished the
lactation-induced osteopenia in dams and positively affected BMD and bone
elongation in growing rats. Therefore, presuckling calcium supplementation in
lactating mothers is an effective strategy for promoting a long-lasting high bone
density for both mother and the offspring.
PMID- 25852003
TI - Systemic alterations in the metabolome of diabetic NOD mice delineate increased
oxidative stress accompanied by reduced inflammation and hypertriglyceremia.
AB - Nonobese diabetic (NOD) mice are a commonly used model of type 1 diabetes (T1D).
However, not all animals will develop overt diabetes despite undergoing similar
autoimmune insult. In this study, a comprehensive metabolomic approach,
consisting of gas chromatography time-of-flight (GC-TOF) mass spectrometry (MS),
ultra-high-performance liquid chromatography-accurate mass quadruple time-of
flight (UHPLC-qTOF) MS and targeted UHPLC-tandem mass spectrometry-based
methodologies, was used to capture metabolic alterations in the metabolome and
lipidome of plasma from NOD mice progressing or not progressing to T1D. Using
this multi-platform approach, we identified >1,000 circulating lipids and
metabolites in male and female progressor and nonprogressor animals (n = 71).
Statistical and multivariate analyses were used to identify age- and sex
independent metabolic markers, which best differentiated metabolic profiles of
progressors and nonprogressors. Key T1D-associated perturbations were related
with 1) increases in oxidation products glucono-delta-lactone and galactonic acid
and reductions in cysteine, methionine and threonic acid, suggesting increased
oxidative stress; 2) reductions in circulating polyunsaturated fatty acids and
lipid signaling mediators, most notably arachidonic acid (AA) and AA-derived
eicosanoids, implying impaired states of systemic inflammation; 3) elevations in
circulating triacylglyercides reflective of hypertriglyceridemia; and 4)
reductions in major structural lipids, most notably lysophosphatidylcholines and
phosphatidylcholines. Taken together, our results highlight the systemic
perturbations that accompany a loss of glycemic control and development of overt
T1D.
PMID- 25852005
TI - An index of parameter reproducibility accounting for estimation uncertainty:
theory and case study on beta-cell responsivity and insulin sensitivity.
AB - Parameter reproducibility is necessary to perform longitudinal studies where
parameters are assessed to monitor disease progression or effect of therapy but
are also useful in powering the study, i.e., to define how many subjects should
be studied to observe a given effect. The assessment of parameter reproducibility
is usually accomplished by methods that do not take into account the fact that
these parameters are estimated with uncertainty. This is particularly relevant in
physiological and clinical studies where usually reproducibility cannot be
assessed by multiple testing and is usually assessed from a single replication of
the test. Working in a suitable stochastic framework, here we propose a new index
(S) to measure reproducibility that takes into account parameter uncertainty and
is particularly suited to handle the normal testing conditions of physiological
and clinical investigations. Simulation results prove that S, by properly taking
into account parameter uncertainty, is more accurate and robust than the methods
available in the literature. The new metric is applied to assess reproducibility
of insulin sensitivity and beta-cell responsivity of a mixed-meal tolerance test
from data obtained in the same subjects retested 1 wk apart. Results show that
the indices of insulin sensitivity and beta-cell responsivity to glucose are well
reproducible. We conclude that the oral minimal models provide useful indices
that can be used safely in prospective studies or to assess the efficacy of a
given therapy.
PMID- 25852006
TI - Estradiol-mediated hepatocyte growth factor is involved in the implantation of
endometriotic cells via the mesothelial-to-mesenchymal transition in the
peritoneum.
AB - The pathogenesis of endometriosis, a chronic painful gynecological disease
characterized by the presence of endometrial tissue located outside of the uterus
and often adhering to the peritoneum, is known to be estrogen dependent. However,
the precise pathophysiology of endometriosis remains elusive. Recent studies
indicate that the epithelial-to-mesenchymal transition (EMT) of human endometrial
cells is important for the progression of endometriosis, and another previous
study has implicated hepatocyte growth factor (HGF) in endometriosis progression.
The aim of the present study was to examine the role of estradiol in the
regulation of HGF production and progression of peritoneal endometriosis,
focusing on the interactions between the peritoneum and endometriotic cells.
Consequently, estradiol was found to promote the proliferation, invasion, and
migration of immortalized human endometrial epithelial cells (hEECs) via HGF
upregulation, and the estradiol-induced direct binding of estrogen receptor-alpha
to the HGF promoter was confirmed on a chromatin immunoprecipitation (ChIP)
assay. Estradiol also induced the EMT in hEECs by promoting HGF production.
Furthermore, human mesothelial cells underwent the mesothelial-to-mesenchymal
transition (MMT) during culture with estradiol-stimulated hEEC conditioned
medium. Importantly, estradiol itself did not induce the MMT, and the estradiol
stimulated hEEC-conditioned medium in the presence of HGF antibodies reversed the
MMT process. These results, which were obtained using immortalized hEECs,
indicate that estradiol-induced HGF production may play a crucial role in the
peritoneal implantation of human endometriotic cells by exerting proliferative
and invasive effects via the EMT in hEECs and promoting the MMT in mesothelial
cells.
PMID- 25852007
TI - ATGL-mediated triglyceride turnover and the regulation of mitochondrial capacity
in skeletal muscle.
AB - Emerging evidence indicates that skeletal muscle lipid droplets are an important
control point for intracellular lipid homeostasis and that regulating fatty acid
fluxes from lipid droplets might influence mitochondrial capacity. We used
pharmacological blockers of the major triglyceride lipases, adipose triglyceride
lipase (ATGL) and hormone-sensitive lipase, to show that a large proportion of
the fatty acids that are transported into myotubes are trafficked through the
intramyocellular triglyceride pool. We next tested whether increasing lipolysis
from intramyocellular lipid droplets could activate transcriptional responses to
enhance mitochondrial and fatty acid oxidative capacity. ATGL was overexpressed
by adenoviral and adenoassociated viral infection in C2C12 myotubes and the
tibialis anterior muscle of C57Bl/6 mice, respectively. ATGL overexpression in
C2C12 myotubes increased lipolysis, which was associated with increased
peroxisome proliferator-activated receptor (PPAR)-? activity, transcriptional
upregulation of some PPAR? target genes, and enhanced mitochondrial capacity. The
transcriptional responses were specific to ATGL actions and not a generalized
increase in fatty acid flux in the myotubes. Marked ATGL overexpression (20-fold)
induced modest molecular changes in the skeletal muscle of mice, but these
effects were not sufficient to alter fatty acid oxidation. Together, these data
demonstrate the importance of lipid droplets for myocellular fatty acid
trafficking and the capacity to modulate mitochondrial capacity by enhancing
lipid droplet lipolysis in vitro; however, this adaptive program is of minor
importance when superimposing the normal metabolic stresses encountered in free
moving animals.
PMID- 25852009
TI - Prognostic significance of autocrine motility factor receptor expression by
colorectal cancer and lymph node metastases.
AB - BACKGROUND: Autocrine motility factor receptor (AMFR) has been linked to
metastasis and tumorigenicity. The aim of this study was to evaluate expression
and prognostic significance of AMFR in colorectal carcinoma. METHODS: AMFR
expression was evaluated in 127 colon cancer specimens, 131 rectal cancer
specimens, and 47 colonic and 25 rectal corresponding lymph node metastases.
Clinicopathological correlates of prognostic significance were established by
univariate and multivariate analysis. Spearman's correlation determined the
association of expression between cancers and their metastases. RESULTS: AMFR was
over-expressed by 22% of colon cancers and 18% of rectal cancers. AMFR over
expression correlated significantly with improved disease-free survival (DFS) (P
< .05) in colon cancer and decreased DFS in corresponding nodal metastases. In
rectal cancer, AMFR over-expression significantly correlated with decreased
overall survival, DFS, and disease-specific survival (P < .001, P = .031, P =
.005, respectively) and decreased overall survival in corresponding metastases.
CONCLUSION: AMFR may serve as a molecular prognosticator for colon cancer and
rectal cancer.
PMID- 25852008
TI - Long-chain acylcarnitines activate cell stress and myokine release in C2C12
myotubes: calcium-dependent and -independent effects.
AB - Acylcarnitines, important lipid biomarkers reflective of acyl-CoA status, are
metabolites that possess bioactive and inflammatory properties. This study
examined the potential for long-chain acylcarnitines to activate cellular
inflammatory, stress, and death pathways in a skeletal muscle model.
Differentiated C2C12 myotubes treated with l-C14, C16, C18, and C18:1 carnitine
displayed dose-dependent increases in IL-6 production with a concomitant rise in
markers of cell permeability and death, which was not observed for shorter chain
lengths. l-C16 carnitine, used as a representative long-chain acylcarnitine at
initial extracellular concentrations >=25 MUM, increased IL-6 production 4.1-,
14.9-, and 31.4-fold over vehicle at 25, 50, and 100 MUM. Additionally, l-C16
carnitine activated c-Jun NH2-terminal kinase, extracellular signal-regulated
kinase, and p38 mitogen-activated protein kinase between 2.5- and 11-fold and
induced cell injury and death within 6 h with modest activation of the apoptotic
caspase-3 protein. l-C16 carnitine rapidly increased intracellular calcium, most
clearly by 10 MUM, implicating calcium as a potential mechanism for some
activities of long-chain acylcarnitines. The intracellular calcium chelator BAPTA
AM blunted l-C16 carnitine-mediated IL-6 production by >65%. However, BAPTA-AM
did not attenuate cell permeability and death responses, indicating that these
outcomes are calcium independent. The 16-carbon zwitterionic compound
amidosulfobetaine-16 qualitatively mimicked the l-C16 carnitine-associated cell
stress outcomes, suggesting that the effects of high experimental concentrations
of long-chain acylcarnitines are through membrane disruption. Herein, a model is
proposed in which acylcarnitine cell membrane interactions take place along a
spectrum of cellular concentrations encountered in physiological-to
pathophysiological conditions, thus regulating function of membrane-based systems
and impacting cell biology.
PMID- 25852010
TI - Prognostic value of volume-based measurements on (11)C-methionine PET in glioma
patients.
AB - PURPOSE: (11)C-methionine (MET) PET is an established diagnostic tool for glioma.
Studies have suggested that MET uptake intensity in the tumor is a useful index
for predicting patient outcome. Because MET uptake is known to reflect tumor
expansion more accurately than MRI, we aimed to elucidate the association between
volume-based tumor measurements and patient prognosis. METHODS: The study
population comprised 52 patients with newly diagnosed glioma who underwent PET
scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a
threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic
tumor volume (MTV) was defined as the total volume within the boundary. Total
lesion methionine uptake (TLMU) was defined as MTV times the mean standardized
uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR),
calculated as the maximum standardized uptake value (SUVmax) divided by the
contralateral reference value, was also recorded. All patients underwent surgery
(biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan
Meier method was used to estimate the predictive value of each measurement.
RESULTS: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2
oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8
anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic
oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and
TLMU were 3.1 +/- 1.2, 51.6 +/- 49.9 ml and 147.7 +/- 153.3 ml, respectively.
None of the three measurements was able to categorize the glioma patients in
terms of survival when all patients were analyzed. However, when only patients
with astrocytic tumor (N = 33) were analyzed (i.e., when those with
oligodendroglial components were excluded), MTV and TLMU successfully predicted
patient outcome with higher values associated with a poorer prognosis (P < 0.05
and P < 0.01, respectively), while the predictive ability of TNR did not reach
statistical significance (P = NS). CONCLUSION: MTV and TLMU may be useful for
predicting outcome in patients with astrocytic tumor.
PMID- 25852012
TI - European and international links.
PMID- 25852011
TI - Thoracic staging of non-small-cell lung cancer using integrated (18)F-FDG PET/MR
imaging: diagnostic value of different MR sequences.
AB - PURPOSE: To compare the accuracy of different MR sequences in simultaneous PET/MR
imaging for T staging in non-small-cell lung cancer in relation to
histopathology. METHODS: The study included 28 patients who underwent dedicated
thoracic PET/MR imaging before tumour resection. Local tumour staging was
performed separately by three readers with each of the following MR sequences
together with PET: transverse T2 BLADE, transverse non-enhanced and contrast
enhanced T1 FLASH, T1 3D Dixon VIBE in transverse and coronal orientation,
coronal T2 HASTE, and coronal TrueFISP. The staging results were compared with
histopathology after resection as the reference standard. Differences in the
accuracy of T staging among the MR sequences were evaluated using McNemar's test.
Due to multiple testing, Bonferroni correction was applied to prevent
accumulation of alpha errors; p < 0.0024 was considered statistically
significant. RESULTS: Compared with histopathology, T-staging accuracy was 69%
with T2 BLADE, 68% with T2 HASTE, 59% with contrast-enhanced T1 FLASH, 57% with
TrueFISP, 50 % with non-enhanced T1 FLASH, and 45% and 48% with T1 3D Dixon VIBE
in transverse and coronal orientation, respectively. Staging accuracy with T2
BLADE was significantly higher than with non-enhanced T1 FLASH and with T1 3D
Dixon VIBE in transverse and coronal orientations (p < 0.0024). T2 HASTE had a
significantly higher T-staging accuracy than transverse T1 3D-Dixon-VIBE (p <
0.0024). CONCLUSION: Transverse T2 BLADE images provide the highest accuracy for
local tumour staging and should therefore be included in dedicated thoracic
PET/MR protocols. As T1 3D Dixon VIBE images acquired for attenuation correction
performed significantly worse, this sequence cannot be considered sufficiently
accurate for local tumour staging in the thorax.
PMID- 25852013
TI - Commentary on Singh et al. Nonunion after trapeziometacarpal arthrodesis:
comparison between K-wire and internal fixation and Smeraglia et al.
Trapeziometacarpal arthrodesis: is bone union necessary for a good outcome?
PMID- 25852014
TI - Re: Renfree KJ. Percutaneous in situ versus open arthrodesis of the distal
interphalangeal joint. J Hand Surg Eur. Epub ahead of print 18 March 2014. DOI:
10.1177/1753193414527387.
PMID- 25852015
TI - Re: Tonkin, M. A. On the classification of congenital thumb hypoplasia. J Hand
Surg Eur. 2014, 39: 948-55.
PMID- 25852016
TI - Re: Wong J. and McGrouther D. A. Minimizing trauma over 'no man's land' for
flexor tendon retrieval. J Hand Surg Eur. 2014, 39: 1004-6.
PMID- 25852017
TI - The lost art of single-stage flexor tendon grafting.
PMID- 25852021
TI - Keratinising cystitis with intestinal metaplasia following a Crohn's vesico
intestinal fistula.
PMID- 25852020
TI - Hormone Use, Reproductive History, and Risk of Lung Cancer: The Women's Health
Initiative Studies.
AB - INTRODUCTION: Results from the Women's Health Initiative clinical trials
demonstrated no increase in the risk of lung cancer in postmenopausal women
treated with hormone therapy (HT). We conducted a joint analysis of the Women's
Health Initiative observational study data and clinical trials data to further
explore the association between estrogen and estrogen-related reproductive
factors and lung cancer risk. METHODS: Reproductive history, oral contraceptive
use, and postmenopausal HT were evaluated in 160,855 women with known HT
exposures. Follow-up for lung cancer was through September 17, 2012; 2467
incident lung cancer cases were ascertained, with median follow-up of 14 years.
RESULTS: For all lung cancers, women with previous use of estrogen plus progestin
of less than 5 years (hazard ratio = 0.84; 95% confidence interval = 0.71-0.99)
were at reduced risk. A limited number of reproductive factors demonstrated
associations with risk. There was a trend toward decreased risk with increasing
age at menopause (ptrend = 0.04) and a trend toward increased risk with
increasing number of live births (ptrend = 0.03). Reduced risk of non-small-cell
lung cancer was associated with age 20-29 years at first live birth. Risk
estimates varied with smoking history, years of HT use and previous bilateral
oophorectomy. CONCLUSIONS: Indirect measures of estrogen exposure to lung tissue,
as used in this study, provide only weak evidence for an association between
reproductive history or HT use and risk of lung cancer. More detailed mechanistic
studies and evaluation of risk factors in conjunction with estrogen receptor
expression in the lung should continue as a role for estrogen cannot be ruled out
and may hold potential for prevention and treatment strategies.
PMID- 25852022
TI - Advantages of single-puncture transperineal saturation biopsy of prostate:
analysis of outcomes in 125 patients using our scheme.
AB - PURPOSE: Stereotactic biopsy has improved prostate cancer detection. Although the
new approach is superior, standard procedure is still useful in a cohort of
patients in whom MRI is not available. The standard saturation biopsy technique
is still debatable. We describe our technique and analyze its outcomes. MATERIALS
AND METHODS: One hundred twenty-five patients underwent saturation biopsy through
a single transperineal access. Mean age was 64.73 year, mean PSA was 9.49 ng/ml,
mean PSA density was 0.184, and mean prostate volume was 57.95 g. All patients
underwent at least one previous prostatic biopsy: 24.8% of cases had diagnosis of
atypical small acinar proliferation, 39.2% of cases had multifocal high-grade
prostatic intraepithelial neoplasia, and 36% of cases had inflammation or benign
prostatic hyperplasia. RESULTS: The detection rate was 38.4%. Prostate cancer
occurred in 61.3% of patients with previous ASAP (p < 0.007). Cancer detection
rate decreased with increasing number of previous biopsy and with increasing
prostate volume (p < 0.001) and increased with increasing PSA density (p = 0.03).
No major complications were reported. CONCLUSION: The traditional saturation
biopsy may be useful when targeted biopsy cannot be used. Our technique is
accurate for cancer detection. It can offer some advantages in comparison with
other approaches.
PMID- 25852023
TI - Aeromonas aquatica sp. nov., Aeromonas finlandiensis sp. nov. and Aeromonas lacus
sp. nov. isolated from Finnish waters associated with cyanobacterial blooms.
AB - Three groups of Aeromonas strains isolated from Finland lakes experiencing
cyanobacterial blooms could not be assigned to any known species of this genus on
the basis of 16S rRNA and rpoD gene sequences. The Multilocus Phylogenetic
Analysis (MLPA) of the concatenated sequence of seven genes (gyrB, rpoD, recA,
dnaJ, gyrA, dnaX and atpD; 4093bp) showed that the three groups of strains did
not cluster with any known Aeromonas spp. and formed three independent lineages.
This was confirmed by performing the analysis with their closest relatives using
15 genes (the latter 7 and cpn60, dnaK, gltA, mdh, radA, rpoB, tsf, zipA;
8751bp). Furthermore, ANI results between the genomes of the type strains of the
three potential new species and those of their close relatives were all <96%
which is the previously proposed cutoff value for differentiating species within
this genus. The in silico DDH values of the three type strains of the new species
also showed a similarity<70% with the most closely related species indicating
they belong to different taxa. The three groups of strains could be
differentiated from each other and from other known Aeromonas species on the
basis of several phenotypic characters. This polyphasic study revealed that the 3
groups of strains represent 3 novel Aeromonas species for which the names
Aeromonas aquatica sp. nov. (type strain AE235T=CECT 8025T=LMG 26712T), Aeromonas
finlandiensis sp. nov. (type strain 4287DT=CECT 8028T=LMG 26709T) and Aeromonas
lacus sp. nov. (type strain AE122T=CECT 8024T=LMG 26710T) are proposed.
PMID- 25852024
TI - Validity of GT3X and Actiheart to estimate sedentary time and breaks using
ActivPAL as the reference in free-living conditions.
AB - Sedentary time, specifically sitting/reclining, is a risk factor for many non
communicable diseases and premature mortality. Inclinometers have been used as a
valid measurement of sedentary time and its patterns; however, there is a lack of
information regarding the validity of alternative accelerometry and heart rate
methods. The validity of GT3X and Actiheart in estimating changes in daily
sedentary time and breaks, during free-living settings, using ActivPAL as the
reference was examined. A crossover randomized control trial of an intervention
that aimed to reduce ~3 h/day of sitting time included 10 overweight/obese adults
(37-65 years). Participants had a total of 74 valid days for the three devices
(29 controls; 45 interventions). For ActivPAL, sedentary time was measured
directly based upon posture (sitting/reclining); Actiheart, the presumed MET
cutpoint for sedentary time (<1.5 METs) based on accelerometry+heart rate; GT3X,
the traditional <100countsmin(-1). A break in sedentary time was defined as when
the participants were above the aforementioned cutoffs. GT3X overestimated and
Actiheart underestimated sedentary time (bias=135min; bias=-156min, respectively)
and both methods overestimated breaks in sedentary time (bias=78; bias=235
breaks, respectively). The GT3X method was in better agreement with the ActivPAL
sedentary time (r2=0.70; concordance correlation coefficient (CCC)=0.56) than the
Actiheart (r2=0.24; CCC=0.31). The present results highlight the magnitude of
potential errors in estimating sedentary time and breaks from common alternative
methods other than ActivPAL. Because misclassification errors from the commonly
used surrogates are potentially large, this raises concern that alternative
methods used in many epidemiological observations may have underestimated the
true effects caused by too much sitting (ClinicalTrials.govID:NCT02007681).
PMID- 25852025
TI - Plasma glucose kinetics and response of insulin and GIP following a cereal
breakfast in female subjects: effect of starch digestibility.
AB - BACKGROUND/OBJECTIVES: Foods with high contents of slowly digestible starch (SDS)
elicit lower glycemic responses than foods with low contents of SDS but there has
been debate on the underlying changes in plasma glucose kinetics, that is,
respective contributions of the increase in the rates of appearance and
disappearance of plasma glucose (RaT and RdT), and of the increase in the rate of
appearance of exogenous glucose (RaE) and decrease in endogenous glucose
production (EGP). SUBJECTS/METHODS: Sixteen young healthy females ingested in
random order four types of breakfasts: an extruded cereal (0.3% SDS: Lo-SDS
breakfast) or one of three biscuits (39-45% SDS: Hi-SDS breakfasts). The flour in
the cereal products was labeled with (13)C, and plasma glucose kinetics were
measured using [6,6-(2)H2]glucose infusion, along with the response of plasma
glucose, insulin and glucose-dependent insulinotropic peptide (GIP)
concentrations. RESULTS: When compared with the Lo-SDS breakfast, after the three
Hi-SDS breakfasts, excursions in plasma glucose, the response of RaE, RaT and
RdT, and the reduction in EGP were significantly lower (P<0.05). The amount of
exogenous glucose absorbed over the 4.5-h postprandial period was also
significantly lower by ~31% (P<0.001). These differences were associated with
lower responses of GIP and insulin concentrations. CONCLUSIONS: Substituting
extruded cereals with biscuits slows down the availability of glucose from the
breakfast and its appearance in peripheral circulation, blunts the changes in
plasma glucose kinetics and homeostasis, reduces excursions in plasma glucose,
and possibly distributes the glucose ingested over a longer period following the
meal.
PMID- 25852027
TI - Prenatal exposure to vitamin-D from fortified margarine and milk and body size at
age 7 years.
AB - BACKGROUND/OBJECTIVES: Prenatal vitamin-D deficiency may be associated with
increased risk of obesity later in life. Using two national vitamin-D
fortification programs as the setting for a societal experiment, we investigated
whether exposure to vitamin-D from fortified margarine and low-fat milk during
foetal life was associated with body size at 7 years of age. SUBJECTS/METHODS:
Vitamin-D fortification of margarine was mandatory in Denmark from 1961 to 1985,
and voluntary fortification of low-fat milk was permitted from 1972 to 1976.
Using information on body mass index (BMI) Z-score at the age of 7 years of
54,270 children, who were measured during the mandatory Copenhagen School Health
examination, we compared children according to whether the mothers were pregnant
during the fortification programs or not. The comparisons were performed for
children born just before and after initiation or termination of margarine and
milk fortification periods, respectively. In total four sets of analyses were
performed. RESULTS: We observed no difference in mean BMI Z-score between
children exposed to vitamin-D fortification in utero and non-exposed children.
Similar results were observed for overweight and obesity. CONCLUSIONS: Prenatal
exposure to vitamin-D from fortification of margarine and low-fat milk showed no
association with body size at 7 years.
PMID- 25852026
TI - Colors of fruits and vegetables and 3-year changes of cardiometabolic risk
factors in adults: Tehran lipid and glucose study.
AB - BACKGROUND/OBJECTIVES: We aimed to investigate the associations of colors of
fruit and vegetable (FV) subgroups, with 3-year changes of cardiometabolic risk
factors. SUBJECTS/METHODS: This longitudinal study was conducted in the framework
of Tehran Lipid and Glucose Study, between 2006-2008 and 2009-2011, on 1272
adults. Total intake of FV and their subgroups have been assessed by a validated
semi-quantitative food frequency questionnaire at baseline (2006-2008) and again
at the second examination (2009-2011). Demographics, anthropometrics and
biochemical measures were evaluated at baseline and 3 years later. The
associations of anthropometric and lipid profile changes with FV subgroups were
estimated. RESULTS: The mean age of men and women at baseline was 39.8+/-12.7 and
37.3+/-12.1 years, respectively. Mean total intake of FV, red/purple, yellow,
green, orange and white FV was 706+/-337, 185+/-95, 141+/-91, 152+/-77, 141+/-87
and 22+/-18 g/day, respectively. In men, 3-year changes of weight (beta=-0.13,
P=0.01) and waist circumference (beta=-0.14, P=0.01) were related to intake of
red/purple FV; the yellow group was inversely associated with 3-year changes of
total cholesterol (beta=-0.09, P=0.03) and High-density lipoprotein cholesterol
(beta=-0.11, P=0.03). Consumption of green and white FV was inversely related to
abdominal fat gain, and atherogenic lipid parameters in men (P<0.05). In women,
higher intake of red/purple FV was associated to lower weight and abdominal fat
gain, fasting serum glucose and total cholesterol (P<0.05); yellow FV was also
related to 3-year weight gain (beta=-0.11, P=0.01). CONCLUSIONS: Various colors
of FV subgroups had different effects on cardiometabolic risk factors; higher
intake of red/purple FV may be related to lower weight and abdominal fat gain,
and yellow, green and white FV may be related to lipid parameters.
PMID- 25852028
TI - Preliminary validation and principal components analysis of the Control of Eating
Questionnaire (CoEQ) for the experience of food craving.
AB - BACKGROUND/OBJECTIVES: The Control of Eating Questionnaire (CoEQ) comprises 21
items that are designed to assess the severity and type of food cravings an
individual experiences over the previous 7 days. The CoEQ has been used in
clinical trials as a multi-dimensional measure of appetite, craving and mood
regulation however its underlying component structure has yet to be determined.
The current paper has two aims; (1) to examine the psychometric properties, and
internal consistency of the CoEQ; and (2) to provide a preliminary examination of
the underlying components by exploring their construct and predictive validity.
SUBJECTS/METHODS: Data were pooled from four studies in which a total 215 adults
(80% women; Age=29.7 +/- 10.3; BMI=26.5 +/- 5.2) had completed the CoEQ alongside
measures of psychometric eating behaviour traits, ad libitum food intake, and
body composition. A principal components analysis (PCA) and parallel analysis was
conducted to examine the underlying structure of the questionnaire. The resulting
subscales were tested for internal consistency (Cronbach's alpha=0.66-0.88).
RESULTS: PCA revealed four components that explained 54.5% of the variance. The
components were identified as: Craving Control, Positive Mood, Craving for Sweet,
and Craving for Savoury. Associations between the underlying CoEQ subscales and
measures of body composition and eating behaviour traits confirmed construct
validity of the subscales. The associations between the subscales and snack food
selection and intake of palatable snack foods supported the CoEQ's predictive
validity. CONCLUSIONS: The CoEQ has good psychometric properties with a clear
component structure and acceptable internal consistency. This preliminary
validation supports the CoEQ as a measure of the experience of food cravings.
PMID- 25852029
TI - Hexasomy 13q31.3q34 due to two marker chromosomes with inverted duplication in a
fetus with increased nuchal translucency.
AB - BACKGROUND: Small supernumerary marker chromosomes are structurally rearranged
chromosomes that can be formed from different chromosomal fragments and cannot be
identified using chromosomal banding analysis. Their examination has to be
complemented by additional analyses like fluorescent in situ hybridization or
array comparative genomic hybridization. METHODS: We report on partial hexasomy
of chromosome 13q in a fetus of a pregnant woman referred to genetic counseling
because of increased fetal nuchal translucency and increased risk of trisomy 21
and trisomy 18 in first-trimester combined prenatal screening. Using chromosome
banding analysis, in situ hybridization and array comparative hybridization we
revealed the presence of two marker chromosomes with inverted duplication
resulting in hexasomy of a 22.6 Mbp fragment in chromosomal region 13q31.3-13q34
with the lack of chromosome 13 centromere. RESULTS: The fetus presented
dysmorphic facial features, head and body disproportion, wide neck, ambiguous
genitalia, incorrect position of the anus, and symmetrical shortening of the long
bones were present in our described case. Some of these features were in
accordance with other published cases. Other most often described features in
tetrasomy were: microphtalmia or other major eye defects, ear abnormalities and
deafness, hemangiomata, hypotelorism, severe learning disability and seizures.
Despite a low risk of recurrence for small supernumerary marker chromosomes the
possibility of germ line mosaicism exists, thus genetic counseling was offered to
the examined family. CONCLUSION: A full characterization of small supernumerary
marker chromosomes in fetal karyotype is necessary for pregnancy prognosis and
genetic counseling.
PMID- 25852031
TI - What isn't said.
PMID- 25852030
TI - Construction and validation of the My Medicines and Me Questionnaire for
assessment of the self-reported side effects of psychotropic medication.
AB - We aimed to construct and assess the psychometric properties of the My Medicines
and Me Questionnaire (M3Q), a self-report side-effect questionnaire for mental
health patients. Thirty individuals taking a psychotropic medication completed
the M3Q side-effect checklist along with the Liverpool University Neuroleptic
Side Effect Rating Scale. Thirty healthy comparison individuals also completed
the M3Q checklist. Data were analyzed using factorial analysis. Psychometric
evaluations including validity and reliability testing were carried out on the
questionnaire's checklist. The original 54-item checklist of the M3Q was
shortened to include only those items found to be significant in the factorial
analysis. The revised 32-item checklist of the M3Q was found to be valid and
reliable. The M3Q is a simple, valid and reliable questionnaire that can be used
routinely in clinical practice for detecting bothersome side effects of a range
of psychotropic medications. This will provide a platform for improved
communication between the clinician and the patient.
PMID- 25852032
TI - Doctors urged to improve Aboriginal child health.
PMID- 25852033
TI - Advancing social media in medical education.
PMID- 25852034
TI - Nova Scotia sets direction on GPS monitoring of patients.
PMID- 25852035
TI - Health professionalism must be ensured online and offline.
PMID- 25852036
TI - Peanut and fish allergy due to platelet transfusion in a child.
PMID- 25852037
TI - Elder abuse: an approach to identification, assessment and intervention.
PMID- 25852038
TI - The resurgence of pertussis.
PMID- 25852039
TI - Is Canada's drug safety network effective?
PMID- 25852041
TI - Catalysts of worker-to-worker violence and incivility in hospitals.
AB - AIMS AND OBJECTIVES: To identify common catalysts of worker-to-worker violence
and incivility in hospital settings. BACKGROUND: Worker-to-worker violence and
incivility are prevalent forms of mistreatment in healthcare workplaces. These
are forms of counterproductive work behaviour that can lead to negative outcomes
for employees, patients and the organisation overall. Identifying the factors
that lead to co-worker mistreatment is a critical first step in the development
of interventions targeting these behaviours. DESIGN: Retrospective descriptive
study. METHODS: Qualitative content analysis was conducted on the total sample (n
= 141) of employee incident reports of worker-to-worker violence and incivility
that were documented in 2011 at a large American hospital system. RESULTS: More
than 50% of the incidents involved nurses, and the majority of incidents did not
involve physical violence. Two primary themes emerged from the analysis: Work
Behaviour and Work Organisation. Incidents in the Work Behaviour category were
often sparked by unprofessional behaviour, disagreement over responsibilities for
work tasks or methods of patient care, and dissatisfaction with a co-worker's
performance. Incidents in the Work Organisation category involved conflicts or
aggression arising from failure to following protocol, patient assignments,
limited resources and high workload. CONCLUSION: Incidents of worker-to-worker
violence and incivility stemmed from dissatisfaction with employee behaviour or
from organisational practices or work constraints. These incident descriptions
reflect worker dissatisfaction and frustration, resulting from poor communication
and collaboration between employees, all of which threaten work productivity.
RELEVANCE TO CLINICAL PRACTICE: Violence and incivility between hospital
employees can contribute to turnover of top performers, hinder effective teamwork
and jeopardise the quality of patient care. Identification of common catalysts
for worker-to-worker violence and incivility informs the development of
mistreatment prevention programmes that can be used to educate hospital staff.
PMID- 25852042
TI - Complex surgical therapy of multiple trichoepitheliomas.
PMID- 25852043
TI - Atom-precise polyoxometalate-ag2 s core-shell nanoparticles.
AB - Atomically precise polyoxometalate-Ag2 S core-shell nanoparticles were generated
in a top-down approach under solvothermal conditions and structurally confirmed
by X-ray single-crystal diffraction as an interesting core-shell structure
comprising an in situ generated Mo6 O22 (8-) polyoxometalate core and a mango
like Ag58 S38 shell. This result demonstrates the possibility to integrate
polyoxometalate and Ag2 S nanoparticles into a core-shell heteronanostructure
with precisely controlled atomical compositions of both core and shell.
PMID- 25852044
TI - Chronic helminth infection and helminth-derived egg antigens promote adipose
tissue M2 macrophages and improve insulin sensitivity in obese mice.
AB - Chronic low-grade inflammation associated with obesity contributes to insulin
resistance and type 2 diabetes. Helminth parasites are the strongest natural
inducers of type 2 immune responses, and short-lived infection with rodent
nematodes was reported to improve glucose tolerance in obese mice. Here, we
investigated the effects of chronic infection (12 weeks) with Schistosoma
mansoni, a helminth that infects millions of humans worldwide, on whole-body
metabolic homeostasis and white adipose tissue (WAT) immune cell composition in
high-fat diet-induced obese C57BL/6 male mice. Our data indicate that chronic
helminth infection reduced body weight gain (-62%), fat mass gain (-89%), and
adipocyte size; lowered whole-body insulin resistance (-23%) and glucose
intolerance (-16%); and improved peripheral glucose uptake (+25%) and WAT insulin
sensitivity. Analysis of immune cell composition by flow cytometry and
quantitative PCR (qPCR) revealed that S. mansoni promoted strong increases in WAT
eosinophils and alternatively activated (M2) macrophages. Importantly, injections
with S. mansoni-soluble egg antigens (SEA) recapitulated the beneficial effect of
parasite infection on whole-body metabolic homeostasis and induced type 2 immune
responses in WAT and liver. Taken together, we provide novel data suggesting that
chronic helminth infection and helminth-derived molecules protect against
metabolic disorders by promoting a T helper 2 (Th2) response, eosinophilia, and
WAT M2 polarization.
PMID- 25852045
TI - Alcohol Prevention and School Students: Findings From an Australian 2-Year Trial
of Integrated Harm Minimization School Drug Education.
AB - The Drug Education in Victorian Schools program provided integrated education
about licit and illicit drugs, employed a harm minimization approach that
incorporated participatory, critical thinking and skill-based teaching methods,
and engaged parental influence through home activities. A cluster-randomized,
controlled trial of the program was conducted with a student cohort during Year 8
(13 years) and Year 9 (14 years). Twenty-one secondary schools in Victoria,
Australia, were randomly allocated to the Drug Education in Victorian Schools
program (14 schools, n = 1,163) or their usual drug education program (7 schools,
n = 589). This study reports program effects for alcohol. There was a greater
increase in the intervention students' knowledge about drugs, including alcohol;
there was a greater increase in communication with parents about alcohol; they
recalled receiving more alcohol education; their alcohol consumption increased
less; and they experienced a lesser increase in alcohol-related harms. Among
intervention group risky drinkers, consumption and harm increased less. There
were no differences between study groups in attitudes toward alcohol or in the
proportion of drinkers or risky drinkers. While the program did not stop students
taking up drinking, it did reduce their consumption and harm.
PMID- 25852046
TI - Complex abdominopelvic endometriosis: the radiologist's perspective.
AB - Endometriosis is a multifocal gynecological disorder affecting approximately 6%
10% of women during their reproductive years (Giudice and Kao in: Lancet 364:1789
1799, 2004). Presenting symptomatology often relates to the anatomical structures
involved. Given the complexity of both the management and pain control of
patients with complex endometriosis, the British Society of Gynaecological
Endoscopy has issued guidelines on the establishment of a multidisciplinary team
approach to these cases (http://www.bsge.org.uk/ec-requirements-BSGE-accredited
endometriosis-centre.php). The ovaries are the most common site affected, but the
gastrointestinal, genitourinary tract, chest and other soft tissues are not
infrequently involved. Less well-recognized features of the disease include the
deep infiltrative form of endometriosis, malignant transformation and
decidualization of endometriomas under progesterone. In this pictorial essay, we
will discuss the clinical presentation and review the imaging features of these
complex and under appreciated forms of endometriotic disease.
PMID- 25852047
TI - CT-based assessment of renal function impairment in patients with acute
unilateral ureteral obstruction by urinary stones.
AB - PURPOSE: The purpose of our study was to evaluate computed tomography (CT)
imaging factors related to renal function impairment in patients with acute
unilateral ureteral obstruction by urinary stones. MATERIALS AND METHODS: The
study included 94 patients who had acute unilateral ureteral obstruction due to a
urinary stone and a normal contralateral kidney. We retrospectively investigated
the serum creatinine (SCr) levels immediately prior to CT examination and at
least 1 week after treatment. CT examinations were performed using a CT urography
protocol, including pre- and post-contrast images. The 67 patients with a SCr
change of less than 0.3 mg/dL constituted group A. The other 27 patients with a
SCr decrease of more than 0.3 mg/dL constituted group B. To evaluate factors
related to renal function impairment, differences in CT imaging factors between
the two groups, including the cortical and medullary density, renal and pelvic
anteroposterior diameter, and perinephric fluid, were statistically analyzed.
RESULTS: The SCr immediately prior to CT examination significantly differed
between the two groups. The follow-up SCr after resolution did not significantly
differ between the two groups. The difference in the mean cortical and medullary
HU on the nephrographic phase between the obstructed kidney and normal kidney was
higher in group B than in group A (27.1 +/- 23.1 and 69.4 +/- 59.1 vs. 5.7 +/-
8.8 and 31.8 +/- 34.8; p < 0.001 and p = 0.004, respectively). The cut-off point
for the difference in the mean cortical HU on the nephrographic phase between the
obstructed kidney and normal kidney for renal function impairment was 15 HU, as
determined by a receiver operating characteristic curve analysis. CONCLUSIONS:
Patients with significantly impaired renal function due to an acute unilateral
ureteral obstruction may show a decreased nephrogram of the affected kidney and a
significant difference in the HU on the nephrographic phase between the
obstructed and normal kidney.
PMID- 25852048
TI - Herlyn-Werner-Wunderlich syndrome: pre- and post-surgical MRI and US findings.
AB - Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital anomaly of the
female urogenital tract that associates Mullerian duct anomalies with mesonephric
duct anomalies. The triad of uterus didelphys, obstructed hemivagina, and
ipsilateral renal agenesis characterizes this syndrome. Patients generally
present with non-specific symptoms after menarche. Pelvic pain, dysmenorrhea, and
palpable mass due to hematocolpos or hematometra are the most common findings.
Pyohematocolpos and pyosalpinx may appear as acute complications, while
endometriosis and pelvic adhesions constitute potential long-term complications.
When a prenatal diagnosis of unilateral renal agenesis in newborn girls is known,
a gynecological imaging study should be performed to exclude uterine and vaginal
abnormalities. These patients should be followed up to ensure that a timely
surgical correction is performed. The diagnosis of HWWS is difficult due to the
lack of specific symptoms or findings upon physical examination. An accurate
imaging description of these congenital anomalies is crucial to guide patients
toward surgical treatment, relieving acute complications, and preserving the
normal fertility. The authors provide a pictorial review of the magnetic
resonance imaging and ultrasonography findings of the HWWS with correlation to
embryological, clinical, and surgical features.
PMID- 25852049
TI - Employers' attitudes on hiring workers with intellectual disabilities in small
and medium enterprises: an Italian research.
AB - Employers play a significant role in the process of hiring workers with
intellectual disability. Through an in-depth interview, this research aims to
investigate the attitudes of 30 representatives of small and medium-sized Italian
companies involved in a process of recruitment. The data were analyzed using a
phenomenological approach. The results show that attitudes toward the disabled
employee are influenced by three areas, namely, personal characteristics of
employers, selection process, and concerns and opinions of employers.
PMID- 25852050
TI - Cumulative dose of hydroxychloroquine is associated with a decrease of resting
heart rate in patients with systemic lupus erythematosus: a pilot study.
AB - INTRODUCTION: The use of hydroxychloroquine (HCQ) in patients with systemic lupus
erythematosus (SLE) offers a wide range of benefits. However, there are evidence
in favour of cardiotoxicity, including heart conduction disturbances and
congestive heart failure. OBJECTIVE: To determine the effects of HCQ in the
resting heart rate (RHR) of SLE patients. PATIENTS AND METHODS: Included were
patients with non active SLE, with a sedentary lifestyle and treated with HCQ.
Excluded were patients on beta blocker treatment, trained patients, pacemaker's
users and patients with clinical or analytical evidence of anemia, renal disease,
obstructive pulmonary disease, obesity, uncontrolled thyroid disease, fever or
current infection. Standard 12-lead electrocardiogram was performed in the
resting condition (supine decubitus and orthostatic position). Comparison between
groups was performed using Mann-Whitney U test. A multiple linear regression was
performed. A p value <0.05 was considered statistically significant. RESULTS: 42
patients were included. Patients were divided in two groups based on the
cumulative dose of HCQ (CD-HCQ), considering 365 g as cut-off. There were 24
patients with low-HCQ (<365 g) and 18 patients with high-HCQ (>365 g). Non
significant differences were found in age, sex, prednisone dose or SLEDAI. The
mean RHR was 73 +/- 6 beats/min in the low-HCQ and 65 +/- 7 beats/min in the high
HCQ, with a significant decrease of 11% (p = 0.003). In multiple linear
regressions, there were non significant association between the decrease of RHR
and prednisone dose, age, SLEDAI or TSH, but there was significant association
between RHR and CD-HCQ (p = 0.024) and RHR and time of exposure to HCQ (p =
0.029). CONCLUSION: CD-HCQ higher than 365 g was associated with a significant
decrease (11%) in RHR in non-active SLE patients, although a larger prospective
study is required to allow more definitive conclusions.
PMID- 25852051
TI - Ach1 is involved in shuttling mitochondrial acetyl units for cytosolic C2
provision in Saccharomyces cerevisiae lacking pyruvate decarboxylase.
AB - Acetyl-coenzyme A (acetyl-CoA) is not only an essential intermediate in central
carbon metabolism, but also an important precursor metabolite for native or
engineered pathways that can produce many products of commercial interest such as
pharmaceuticals, chemicals or biofuels. In the yeast Saccharomyces cerevisiae,
acetyl-CoA is compartmentalized in the cytosol, mitochondrion, peroxisome and
nucleus, and cannot be directly transported between these compartments. With the
acetyl-carnitine or glyoxylate shuttle, acetyl-CoA produced in peroxisomes or the
cytoplasm can be transported into the cytoplasm or the mitochondria. However,
whether acetyl-CoA generated in the mitochondria can be exported to the cytoplasm
is still unclear. Here, we investigated whether the transfer of acetyl-CoA from
the mitochondria to the cytoplasm can occur using a pyruvate decarboxylase
negative, non-fermentative yeast strain. We found that mitochondrial Ach1 can
convert acetyl-CoA in this compartment into acetate, which crosses the
mitochondrial membrane before being converted into acetyl-CoA in the cytosol.
Based on our finding we propose a model in which acetate can be used to exchange
acetyl units between mitochondria and the cytosol. These results will increase
our fundamental understanding of intracellular transport of acetyl units, and
also help to develop microbial cell factories for many kinds of acetyl-CoA
derived products.
PMID- 25852052
TI - Comparative analysis of human ex vivo-generated platelets vs megakaryocyte
generated platelets in mice: a cautionary tale.
AB - Thrombopoiesis is the process by which megakaryocytes release platelets that
circulate as uniform small, disc-shaped anucleate cytoplasmic fragments with
critical roles in hemostasis and related biology. The exact mechanism of
thrombopoiesis and the maturation pathways of platelets released into the
circulation remain incompletely understood. We showed that ex vivo-generated
murine megakaryocytes infused into mice release platelets within the pulmonary
vasculature. Here we now show that infused human megakaryocytes also release
platelets within the lungs of recipient mice. In addition, we observed a
population of platelet-like particles (PLPs) in the infusate, which include
platelets released during ex vivo growth conditions. By comparing these 2
platelet populations to human donor platelets, we found marked differences:
platelets derived from infused megakaryocytes closely resembled infused donor
platelets in morphology, size, and function. On the other hand, the PLP was a
mixture of nonplatelet cellular fragments and nonuniform-sized, preactivated
platelets mostly lacking surface CD42b that were rapidly cleared by macrophages.
These data raise a cautionary note for the clinical use of human platelets
released under standard ex vivo conditions. In contrast, human platelets released
by intrapulmonary-entrapped megakaryocytes appear more physiologic in nature and
nearly comparable to donor platelets for clinical application.
PMID- 25852053
TI - The role of stem cell transplantation for chronic myelogenous leukemia in the
21st century.
AB - The introduction of tyrosine kinase inhibitors (TKIs), a treatment of chronic
myelogenous leukemia (CML), has largely replaced curative strategies based on
allogeneic stem cell transplantation (SCT). Nevertheless, SCT still remains an
option for accelerated/blastic-phase and selected chronic-phase CML. Transplant
outcomes can be optimized by peritransplant TKIs, conditioning regimen, BCR-ABL
monitoring, and relapse management. Controversies exist in transplant timing,
pediatric CML, alternative donors, and economics. SCT continues to serve as a
platform of "operational cure" for CML with TKIs and immunotherapies.
PMID- 25852054
TI - CMV reactivation drives posttransplant T-cell reconstitution and results in
defects in the underlying TCRbeta repertoire.
AB - Although cytomegalovirus (CMV) reactivation has long been implicated in
posttransplant immune dysfunction, the molecular mechanisms that drive this
phenomenon remain undetermined. To address this, we combined multiparameter flow
cytometric analysis and T-cell subpopulation sorting with high-throughput
sequencing of the T-cell repertoire, to produce a thorough evaluation of the
impact of CMV reactivation on T-cell reconstitution after unrelated-donor
hematopoietic stem cell transplant. We observed that CMV reactivation drove a >50
fold specific expansion of Granzyme B(high)/CD28(low)/CD57(high)/CD8(+) effector
memory T cells (Tem) and resulted in a linked contraction of all naive T cells,
including CD31(+)/CD4(+) putative thymic emigrants. T-cell receptor beta
(TCRbeta) deep sequencing revealed a striking contraction of CD8(+) Tem diversity
due to CMV-specific clonal expansions in reactivating patients. In addition to
querying the topography of the expanding CMV-specific T-cell clones, deep
sequencing allowed us, for the first time, to exhaustively evaluate the
underlying TCR repertoire. Our results reveal new evidence for significant
defects in the underlying CD8 Tem TCR repertoire in patients who reactivate CMV,
providing the first molecular evidence that, in addition to driving expansion of
virus-specific cells, CMV reactivation has a detrimental impact on the integrity
and heterogeneity of the rest of the T-cell repertoire. This trial was registered
at www.clinicaltrials.gov as #NCT01012492.
PMID- 25852056
TI - How I treat refractory and early relapsed acute myeloid leukemia.
AB - Between 10% and 40% of newly diagnosed patients with acute myeloid leukemia (AML)
do not achieve complete remission with intensive induction therapy and are
therefore categorized as primary refractory or resistant. Few of these patients
can be cured with conventional salvage therapy. They need to be evaluated
regarding eligibility for allogeneic hematopoietic stem cell transplantation
(HSCT) as this is currently the treatment with the highest probability of cure.
To reduce the leukemia burden prior to transplantation, salvage chemotherapy
regimens need to be employed. Whenever possible, refractory/relapsed patients
should be enrolled in clinical trials as we do not have highly effective and
standardized treatments for this situation. Novel therapies include tyrosine
kinase inhibitors, small-molecule inhibitors (e.g., for Polo-like kinase 1 and
aminopeptidase), inhibitors of mutated isocitrate dehydrogenase (IDH) 1 and IDH2,
antibody-based therapies, and cell-based therapies. Although the majority of
these therapies are still under evaluation, they are likely to enter clinical
practice rapidly as a bridge to transplant and/or in older, unfit patients who
are not candidates for allogeneic HSCT. In this review, we describe our approach
to refractory/early relapsed AML, and we discuss treatment options for patients
with regard to different clinical conditions and molecular profiles.
PMID- 25852055
TI - Characteristic repartition of monocyte subsets as a diagnostic signature of
chronic myelomonocytic leukemia.
AB - Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/
myeloproliferative neoplasm whose diagnosis is currently based on the elevation
of peripheral blood monocytes to >1 * 10(9)/L, measured for >=3 months. Diagnosis
can be ambiguous; for example, with prefibrotic myelofibrosis or reactive
monocytosis. We set up a multiparameter flow cytometry assay to distinguish
CD14(+)/CD16(-) classical from CD14(+)/CD16(+) intermediate and CD14(low)/CD16(+)
nonclassical monocyte subsets in peripheral blood mononucleated cells and in
total blood samples. Compared with healthy donors and patients with reactive
monocytosis or another hematologic malignancy, CMML patients demonstrate a
characteristic increase in the fraction of CD14(+)/CD16(-) cells (cutoff value,
94.0%). The associated specificity and sensitivity values were 95.1% and 90.6% in
the learning cohort (175 samples) and 94.1% and 91.9% in the validation cohort
(307 samples), respectively. The accumulation of classical monocytes, which
demonstrate a distinct gene expression pattern, is independent of the mutational
background. Importantly, this increase disappears in patients who respond to
hypomethylating agents. We conclude that an increase in the fraction of classical
monocytes to >94.0% of total monocytes is a highly sensitive and specific
diagnostic marker that rapidly and accurately distinguishes CMML from confounding
diagnoses.
PMID- 25852057
TI - Targeting Syk-activated B cells in murine and human chronic graft-versus-host
disease.
AB - Novel therapies for chronic graft-versus-host disease (cGVHD) are needed.
Aberrant B-cell activation has been demonstrated in mice and humans with cGVHD.
Having previously found that human cGVHD B cells are activated and primed for
survival, we sought to further evaluate the role of the spleen tyrosine kinase
(Syk) in cGVHD in multiple murine models and human peripheral blood cells. In a
murine model of multiorgan system, nonsclerodermatous disease with bronchiolitis
obliterans where cGVHD is dependent on antibody and germinal center (GC) B cells,
we found that activation of Syk was necessary in donor B cells, but not T cells,
for disease progression. Bone marrow-specific Syk deletion in vivo was effective
in treating established cGVHD, as was a small-molecule inhibitor of Syk,
fostamatinib, which normalized GC formation and decreased activated CD80/86(+)
dendritic cells. In multiple distinct models of sclerodermatous cGVHD, clinical
and pathological disease manifestations were not eliminated when mice were
therapeutically treated with fostamatinib, though both clinical and immunologic
effects could be observed in one of these scleroderma models. We further
demonstrated that Syk inhibition was effective at inducing apoptosis of human
cGVHD B cells. Together, these data demonstrate a therapeutic potential of
targeting B-cell Syk signaling in cGVHD.
PMID- 25852059
TI - On the Road to Precision Cancer Medicine: Analysis of Genomic Biomarker
Actionability in 439 Patients.
AB - Despite the increased use of molecular diagnostics, the extent to which patients
who have these tests harbor potentially actionable aberrations is unclear. We
retrospectively reviewed 439 patients with diverse cancers, for whom next
generation sequencing (mostly 236-gene panel) had been performed. Data pertaining
to the molecular alterations identified, as well as associated treatment
suggestions (on- or off-label, or experimental), were extracted from molecular
diagnostic reports. Most patients (420/439; 96%) had at least one molecular
alteration: 1,813 alterations (in 207 distinct genes) were identified [the
majority being mutations (62%) or amplifications (29%)]. The three most common
gene abnormalities were TP53 (44%), KRAS (16%), and PIK3CA (12%). The median
number of alterations per patient was 3 (range, 0-16). Nineteen patients (4%) had
no alterations; 48 patients (11%) had only one alteration; and 372 patients had
two or more abnormalities (85%). The median number of potentially actionable
anomalies per patient was 2 (range, 0-8). Most patients (393/439; 90%) had at
least one potentially actionable alteration, and in all these cases the
aberration could at least be targeted by an experimental drug in a clinical
trial. A total of 307 patients (70%) had an alteration that was actionable with
an approved drug, but in only 89 patients (20%) was the drug approved for their
disease (on-label). Next-generation sequencing identified theoretically
actionable aberrations in 90% of our patients. Many of the drugs are, however,
experimental or would require off-label use. Strategies to address drug access
for patients harboring potentially actionable mutations are needed.
PMID- 25852058
TI - CDKN2A/p16 Loss Implicates CDK4 as a Therapeutic Target in Imatinib-Resistant
Dermatofibrosarcoma Protuberans.
AB - Dermatofibrosarcoma protuberans (DFSP) is an aggressive PDGFB-dependent cutaneous
sarcoma characterized by infiltrative growth and frequent local recurrences. Some
DFSP progress to a higher-grade fibrosarcomatous form, with rapid growth and
increased risk of metastasis. Imatinib provides clinical benefit in approximately
50% of patients with unresectable or metastatic DFSP. However, efficacious
medical therapies have not been developed for imatinib-resistant DFSP. We
established a model of imatinib-resistant DFSP and evaluated CDK4/6 inhibition as
a genomically credentialed targeted therapy. DFSP105, an imatinib-resistant human
cell line, was established from a fibrosarcomatous DFSP (FS-DFSP), and was
studied by SNP arrays and sequencing to identify targetable genomic alterations.
Findings were validated in vitro and in vivo, and confirmed in a series including
12 DFSP and 6 FS-DFSP. SNP analysis of DFSP105 revealed a homozygous deletion
encompassing CDKN2A and CDKN2B. The resultant p16 loss implicated CDK4/6 as a
potential therapeutic target in DFSP. We further demonstrated CDKN2A homozygous
deletion in 1 of 12 conventional DFSP and 2 of 6 FS-DFSP, whereas p16 expression
was lost in 4 of 18 DFSP. In vitro treatment of DFSP105 with two structurally
distinct selective CDK4/6 inhibitors, PD-0332991 and LEE011, led to inhibition of
RB1 phosphorylation and inhibition of proliferation (GI50 160 nmol/L and 276
nmol/L, respectively). In vivo treatment of DFSP105 with PD-0332991 (150 mg/kg)
inhibited xenograft growth in mice, in comparison with imatinib-treated or
untreated tumors. In conclusion, CDKN2A deletion can contribute to DFSP
progression. CDK4/6 inhibition is a preclinically effective treatment against p16
negative, imatinib-resistant FS-DFSP, and should be evaluated as a therapeutic
strategy in patients with unresectable or metastatic imatinib-resistant DFSP.
PMID- 25852060
TI - Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein
Kinase D Inhibitor CRT0066101.
AB - Invasive ductal carcinomas (IDC) of the breast are associated with altered
expression of hormone receptors (HR), amplification or overexpression of HER2, or
a triple-negative phenotype. The most aggressive cases of IDC are characterized
by a high proliferation rate, a great propensity to metastasize, and their
ability to resist to standard chemotherapy, hormone therapy, or HER2-targeted
therapy. Using progression tissue microarrays, we here demonstrate that the
serine/threonine kinase protein kinase D3 (PKD3) is highly upregulated in
estrogen receptor (ER)-negative (ER(-)) tumors. We identify direct binding of the
ER to the PRKD3 gene promoter as a mechanism of inhibition of PKD3 expression.
Loss of ER results in upregulation of PKD3, leading to all hallmarks of
aggressive IDC, including increased cell proliferation, migration, and invasion.
This identifies ER(-) breast cancers as ideal for treatment with the PKD
inhibitor CRT0066101. We show that similar to a knockdown of PKD3, treatment with
this inhibitor targets all tumorigenic processes in vitro and decreases growth of
primary tumors and metastasis in vivo. Our data strongly support the development
of PKD inhibitors for clinical use for ER(-) breast cancers, including the triple
negative phenotype.
PMID- 25852061
TI - Recruitment of Oligoclonal Viral-Specific T cells to Kill Human Tumor Cells Using
Single-Chain Antibody-Peptide-HLA Fusion Molecules.
AB - Tumor progression is often associated with the development of diverse immune
escape mechanisms. One of the main tumor escape mechanism is HLA loss, in which
human solid tumors exhibit alterations in HLA expression. Moreover, tumors that
present immunogenic peptides via class I MHC molecules are not susceptible to CTL
mediated lysis, because of the relatively low potency of the tumor-specific CLTs.
Here, we present a novel cancer immunotherapy approach that overcomes these
problems by using the high affinity and specificity of antitumor antibodies to
recruit potent antiviral memory CTLs to attack tumor cells. We constructed a
recombinant molecule by genetic fusion of a cytomegalovirus (CMV)-derived peptide
pp65 (NLVPMVATV) to scHLA-A2 molecules that were genetically fused to a single
chain Fv Ab fragment specific for the tumor cell surface antigen mesothelin. This
fully covalent fusion molecule was expressed in E. coli as inclusion bodies and
refolded in vitro. The fusion molecules could specifically bind mesothelin
expressing cells and mediate their lysis by NLVPMVATV-specific HLA-A2-restricted
human CTLs. More importantly, these molecules exhibited very potent antitumor
activity in vivo in a nude mouse model bearing preestablished human tumor
xenografts that were adoptively transferred along with human memory CTLs. These
results represent a novel and powerful approach to immunotherapy for solid
tumors, as demonstrated by the ability of the CMV-scHLA-A2-SS1(scFv) fusion
molecule to mediate specific and efficient recruitment of CMV-specific CTLs to
kill tumor cells.
PMID- 25852062
TI - Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade
Serous Ovarian Cancer and Sensitivity to PI3K Inhibition.
AB - Identification of genomic alterations defining ovarian carcinoma subtypes may aid
the stratification of patients to receive targeted therapies. We characterized
high-grade serous ovarian carcinoma (HGSC) for the association of amplified and
overexpressed genes with clinical outcome using gene expression data from 499
HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number
amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2,
ZFP36, and URI. The Australian Ovarian Cancer Study and The Cancer Genome Atlas
datasets were also used to assess the correlation between gene expression,
patient survival, and tumor classification. In a multivariate analysis, high GAB2
expression was associated with improved overall and progression-free survival (P
= 0.03 and 0.02), whereas high BMP8B and ATP13A4 were associated with improved
progression-free survival (P = 0.004 and P = 0.02). GAB2 overexpression and copy
number gain were enriched in the AOCS C4 subgroup. High GAB2 expression
correlated with enhanced sensitivity in vitro to the dual PI3K/mTOR inhibitor PF
04691502 and could be used as a genomic marker for identifying patients who will
respond to treatments inhibiting PI3K signaling.
PMID- 25852063
TI - Selective Delivery of PEGylated Compounds to Tumor Cells by Anti-PEG Hybrid
Antibodies.
AB - Polyethylene glycol (PEG) is attached to many peptides, proteins, liposomes, and
nanoparticles to reduce their immunogenicity and improve their pharmacokinetic
and therapeutic properties. Here, we describe hybrid antibodies that can
selectively deliver PEGylated medicines, imaging agents, or nanomedicines to
target cells. Human IgG1 hybrid antibodies alphaPEG:alphaHER2 and
alphaPEG:alphaCD19 were shown by ELISA, FACS, and plasmon resonance to bind to
both PEG and HER2 receptors on SK-BR-3 breast adenocarcinoma and BT-474 breast
ductal carcinoma cells or CD19 receptors on Ramos and Raji Burkitt's lymphoma
cells. In addition, alphaPEG:alphaHER2 specifically targeted PEGylated proteins,
liposomes, and nanoparticles to SK-BR-3 cells that overexpressed HER2, but not to
HER2-negative MCF-7 breast adenocarcinoma cells. Endocytosis of PEGylated
nanoparticles into SK-BR-3 cells was induced specifically by the
alphaPEG:alphaHER2 hybrid antibody, as observed by confocal imaging of the
accumulation of Qdots inside SK-BR-3 cells. Treatment of HER2(+) SK-BR-3 and BT
474 cancer cells with alphaPEG:alphaHER2 and the clinically used chemotherapeutic
agent PEGylated liposomal doxorubicin for 3 hours enhanced the in vitro
effectiveness of PEGylated liposomal doxorubicin by over two orders of magnitude.
Hybrid anti-PEG antibodies offer a versatile and simple method to deliver
PEGylated compounds to cellular locations and can potentially enhance the
therapeutic efficacy of PEGylated medicines.
PMID- 25852064
TI - Physical therapy is as effective as surgery for lumbar spinal stenosis, study
finds.
PMID- 25852065
TI - Aquatic burst locomotion by hydroplaning and paddling in common eiders (Somateria
mollissima).
AB - Common eiders (Somateria mollissima) are heavy sea-ducks that spend a large
portion of their time swimming at the water surface. Surface swimming generates a
bow and hull wave that can constructively interfere and produce wave drag. The
speed at which the wavelengths of these waves equal the waterline length of the
swimming animal is the hull speed. To increase surface swimming speed beyond the
hull speed, an animal must overtake the bow wave. This study found two distinct
behaviors that eider ducks used to exceed the hull speed: (1) 'steaming', which
involved rapid oaring with the wings to propel the duck along the surface of the
water, and (2) 'paddle-assisted flying', during which the ducks lifted their
bodies out of the water and used their feet to paddle against the surface while
flapping their wings in the air. An average hull speed (0.732+/-0.046 m s(-1))
was calculated for S. mollissima by measuring maximum waterline length from
museum specimens. On average, steaming ducks swam 5.5 times faster and paddle
assisted flying ducks moved 6.8 times faster than the hull speed. During
steaming, ducks exceeded the hull speed by increasing their body angle and
generating dynamic lift to overcome wave drag and hydroplane along the water
surface. During paddle-assisted flying, ducks kept their bodies out of the water,
thereby avoiding the limitations of wave drag altogether. Both behaviors provided
alternatives to flight for these ducks by allowing them to exceed the hull speed
while staying at or near the water surface.
PMID- 25852066
TI - Mechanisms and costs of mitochondrial thermal acclimation in a eurythermal
killifish (Fundulus heteroclitus).
AB - Processes acting at the level of the mitochondria have been suggested to affect
the thermal limits of organisms. To determine whether changes in mitochondrial
properties could underlie shifts in thermal limits, we examined how mitochondrial
properties are affected by thermal acclimation in the eurythermal killifish,
Fundulus heteroclitus - a species with substantial plasticity in whole-organism
thermal limits. We hypothesized that thermal acclimation would result in
functional changes in the mitochondria that could result in trade-offs in
function during acute thermal shifts. We measured the mitochondrial respiration
rate (VO2 ) through multiple complexes of the electron transport system following
thermal acclimation (to 5, 15, 33 degrees C) and assessed maintenance of
mitochondrial membrane potential (Deltap) and rates of reactive oxygen species
(ROS) production as an estimate of costs. Acclimation to 5 degrees C resulted in
a modest compensation of mitochondrial respiration at low temperatures, but these
mitochondria were able to maintain Deltap with acute exposure to high
temperatures, and ROS production did not differ between acclimation groups,
suggesting that these increases in mitochondrial capacity do not alter
mitochondrial thermal sensitivity. Acclimation to 33 degrees C suppressed
mitochondrial respiration as a result of effects on NADH dehydrogenase (complex
I). These high-temperature acclimated fish nonetheless maintained levels of
Deltap and ROS production similar to those of the other acclimation groups. This
work demonstrates that killifish mitochondria can successfully acclimate to a
wide range of temperatures without incurring major functional trade-offs during
acute thermal shifts and that high-temperature acclimation results in a
suppression of metabolism, consistent with patterns observed at the organismal
level.
PMID- 25852067
TI - Behaviour of the plathelminth Symsagittifera roscoffensis under different light
conditions and the consequences for the symbiotic algae Tetraselmis convolutae.
AB - Symsagittifera roscoffensis is a plathelminth living in symbiosis with the green
algae Tetraselmis convolutae. Host and symbiont are a model system for the study
of endosymbiosis, which has so far mainly focused on their biochemical
interactions. Symsagittifera roscoffensis is well known for its positive
phototaxis that is hypothesized to optimize the symbiont's light perception for
photosynthesis. In this study, we conducted a detailed analysis of phototaxis
using light sources of different wavelength and brightness by videotracking.
Furthermore, we compared the behavioural data with the electron transfer rate of
the photosystem from cultured symbiotic cells. The symbiotic algae is adapted to
low light conditions, showing a positive electron transfer rate at a
photosynthetically active radiation of 0.112 umol photons m(-2) s(-1), and S.
roscoffensis showed a positive phototactic behaviour for light intensities up to
459.17 umol photons m(-2) s(-1), which is not optimal regarding the needs of the
symbiotic cells and may even harm host and symbiont. Red light cannot be detected
by the animals and therefore their eyes seem not to be suitable for measuring the
exact photosynthetically active radiation to the benefit of the photosymbionts.
PMID- 25852068
TI - Body mass affects seasonal variation in sickness intensity in a seasonally
breeding rodent.
AB - Species that display seasonal variation in sickness intensity show the most
intense response in the season during which they have the highest body mass,
suggesting that sickness intensity may be limited by an animal's energy stores.
Siberian hamsters (Phodopus sungorus) display lower body masses and less intense
sickness when housed in short, winter-like days as opposed to long, summer-like
days. To determine whether reduced sickness intensity displayed by short-day
hamsters is a product of seasonal changes in body mass, we food restricted long
day hamsters so that they exhibited body mass loss that mimicked the natural
photoperiod-induced loss of body mass in short-day hamsters. We then
experimentally induced sickness with lipopolysaccharide (LPS) and compared
sickness responses among long-day food-restricted and long- and short-day ad
libitum fed groups, predicting that long-day food-restricted hamsters would show
sickness responses comparable to those of short-day ad libitum fed hamsters and
attenuated in comparison to long-day ad libitum fed hamsters. We found that long
day food-restricted hamsters showed attenuated LPS-induced anorexia, loss of body
mass and hypothermia compared with long-day ad libitum fed animals; however,
anorexia remained elevated in long-day food-restricted animals compared with
short-day ad libitum fed animals. Additionally, LPS-induced anhedonia and
decreases in nest building were not influenced by body mass. Results of hormone
assays suggest that cortisol levels could play a role in the attenuation of
sickness in long-day food-restricted hamsters, indicating that future research
should target the roles of glucocorticoids and natural variation in energy stores
in seasonal sickness variation.
PMID- 25852069
TI - Vocal performance affects metabolic rate in dolphins: implications for animals
communicating in noisy environments.
AB - Many animals produce louder, longer or more repetitious vocalizations to
compensate for increases in environmental noise. Biological costs of increased
vocal effort in response to noise, including energetic costs, remain empirically
undefined in many taxa, particularly in marine mammals that rely on sound for
fundamental biological functions in increasingly noisy habitats. For this
investigation, we tested the hypothesis that an increase in vocal effort would
result in an energetic cost to the signaler by experimentally measuring oxygen
consumption during rest and a 2 min vocal period in dolphins that were trained to
vary vocal loudness across trials. Vocal effort was quantified as the total
acoustic energy of sounds produced. Metabolic rates during the vocal period were,
on average, 1.2 and 1.5 times resting metabolic rate (RMR) in dolphin A and B,
respectively. As vocal effort increased, we found that there was a significant
increase in metabolic rate over RMR during the 2 min following sound production
in both dolphins, and in total oxygen consumption (metabolic cost of sound
production plus recovery costs) in the dolphin that showed a wider range of vocal
effort across trials. Increases in vocal effort, as a consequence of increases in
vocal amplitude, repetition rate and/or duration, are consistent with behavioral
responses to noise in free-ranging animals. Here, we empirically demonstrate for
the first time in a marine mammal, that these vocal modifications can have an
energetic impact at the individual level and, importantly, these data provide a
mechanistic foundation for evaluating biological consequences of vocal
modification in noise-polluted habitats.
PMID- 25852070
TI - Controlled feeding trials with ungulates: a new application of in vivo dental
molding to assess the abrasive factors of microwear.
AB - Microwear, the quantification of microscopic scratches and pits on the occlusal
surfaces of tooth enamel, is commonly used as a paleodietary proxy. For ungulates
(hoofed mammals), scratch-dominant microwear distinguishes modern grazers from
browsers, presumably as a result of abrasion from grass phytoliths (biogenic
silica). However, it is also likely that exogenous grit (i.e. soil, dust) is a
contributing factor to these scratch-dominant patterns, which may reflect soil
ingestion that varies with feeding height and/or environmental conditions (e.g.
dust production in open and/or arid habitats). This study assessed the
contribution of exogenous grit to tooth wear by measuring the effects of fine-
and medium-grained silica sand on tooth enamel using a novel live-animal tooth
molding technique. It therefore constitutes the first controlled feeding
experiment using ungulates and the first in vivo experiment using abrasives of
different sizes. Four sheep were fed three diet treatments: (1) a mixture of
Garrison and Brome hay (control), (2) hay treated with fine-grained silica sand
(180-250 um) and (3) hay treated with medium-grained silica sand (250-425 um). We
found a significant increase in pit features that was correlated with an increase
in grain size of grit, corroborating earlier chewing simulation experiments that
produced pits through grit-induced abrasion (i.e. the 'grit effect'). Our results
support an interpretation of large silica grains fracturing to create smaller,
more abundant angular particles capable of abrasion, with jaw movement defining
feature shape (i.e. scratch or pit).
PMID- 25852071
TI - Brainstem brain-derived neurotrophic factor signaling is required for histone
deacetylase inhibitor-induced pain relief.
AB - Our previous study demonstrated that persistent pain can epigenetically suppress
the transcription of Gad2 [encoding glutamic acid decarboxylase 65 (GAD65)] and
consequently impair the inhibitory function of GABAergic synapses in central pain
modulating neurons. This contributes to the development of persistent pain
sensitization. Histone deacetylase (HDAC) inhibitors increased GAD65 activity
considerably, restored GABA synaptic function, and rendered sensitized pain
behavior less pronounced. However, the molecular mechanisms by which HDAC
regulates GABAergic transmission through GAD65 under pain conditions are unknown.
This work showed that HDAC inhibitor-induced increases in colocalization of GAD65
and synaptic protein synapsin I on the presynaptic axon terminals of the nucleus
raphe magnus (NRM) were blocked by a TrkB receptor antagonist K252a [(9S,10R,12R)
2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3
fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl
ester], indicating that BDNF-TrkB signaling may be required in GAD65 modulation
of GABA synaptic function. At the brain-derived neurotrophic factor (BDNF)
promoter, HDAC inhibitors induced significant increases in H3 hyperacetylation,
consistent with the increase in BDNF mRNA and total proteins. Although exogenous
BDNF facilitated GABA miniature inhibitory postsynaptic currents and GAD65
accumulation in NRM neuronal synapses in normal rats, it failed to do so in
animals subjected to persistent inflammation. In addition, blockade of the TrkB
receptor with K252a has no effect on miniature inhibitory postsynaptic currents
and synaptic GAD65 accumulation under normal conditions. In addition, the
analgesic effects of HDAC inhibitors on behavior were blocked by NRM infusion of
K252a. These findings suggest that BDNF-TrkB signaling is required for drugs that
reverse the epigenetic effects of chronic pain at the gene level, such as HDAC
inhibitors.
PMID- 25852072
TI - Intentional Large Insulin Overdose Captured on a Continuous Glucose Monitor: A
Novel Case Report.
PMID- 25852073
TI - Holistic Impact of Closed-Loop Technology on People With Type 1 Diabetes.
PMID- 25852074
TI - Rate-of-Change Dependence of the Performance of Two CGM Systems During Induced
Glucose Swings.
AB - INTRODUCTION: The accuracy of continuous glucose monitoring (CGM) systems is
often assessed with respect to blood glucose (BG) readings. CGM readings are
affected by a physiological and a technical time delay when compared to BG
readings. In this analysis, the dependence of CGM performance parameters on the
BG rate of change was investigated for 2 CGM systems. METHODS: Data from a
previously published study were retrospectively analyzed. An established CGM
system (Dexcom G4, Dexcom, San Diego, CA; system A) and a prototype system (Roche
Diagnostics GmbH, Mannheim, Germany; system B) with 2 sensors each were worn by
10 subjects in parallel. Glucose swings were induced to achieve rapidly changing
BG concentrations. Mean absolute relative differences (MARD) were calculated in
different BG rate-of-change categories. In addition, sensor-to-sensor precision
was assessed. RESULTS: At BG rates of change of -1 mg/dl/min to 0 mg/dl/min and 0
mg/dl/min to +1 mg/dl/min, MARD results were 12.6% and 11.3% for system A and
8.2% and 10.0% for system B. At rapidly changing BG concentrations (<-3 mg/dl/min
and >=+3 mg/dl/min), higher MARD results were found for both systems, but system
B was less affected (system A: 24.9% and 29.6%, system B: 10.6% and 16.3%). The
impact of rate of change on sensor-to-sensor precision was less pronounced.
CONCLUSIONS: Both systems were affected by rapidly changing BG concentrations to
some degree, although system B was mostly unaffected by decreasing BG
concentrations. It would seem that technological advancements in CGM systems
might allow for a more precise tracking of BG concentrations even at rapidly
changing BG concentrations.
PMID- 25852075
TI - How to Assess the Quality of Glucose Clamps? Evaluation of Clamps Performed With
ClampArt, a Novel Automated Clamp Device.
AB - BACKGROUND: There are no widely accepted parameters to assess the quality of
glucose clamps. Thus, we selected different parameters describing clamp quality.
These parameters were then evaluated in glucose clamps carried out with ClampArt,
a novel CE-marked, state-of-the-art fully automated glucose clamp device
employing continuous blood glucose (BG) measurements and minute-by-minute
adaptations of glucose infusion rate (GIR). METHODS: Thirty-nine glucose clamps
were performed in 10 healthy and 29 subjects with type 1 diabetes (T1DM) (total
duration 583 h). ClampArt-based BG measurements were compared with those obtained
with a laboratory reference method. Clamp quality was assessed by 5 parameters:
(1) difference (mg/dl) of all paired BG measurements of ClampArt versus reference
method ("trueness"), (2) coefficient of variation (CV, %) of ClampArt's BG
measurements at target clamp level ("precision"), (3) mean absolute relative
difference (MARD, %) at target clamp level ("accuracy"), (4) difference (mg/dl)
between ClampArt and target BG ("control deviation"), and (5) percentage
operational time ("utility"). RESULTS: ClampArt-based BG measurements showed a
trueness of 1.2 +/- 2.5 mg/dl. CV and MARD at target BG were 5.5 +/- 2.1% and 5.3
+/- 2.3%, respectively. There were only small deviations from target level (1.2
+/- 1.6 mg/dl). Operational time was as high as 95.4% +/- 4.1% (means +/- SD).
CONCLUSIONS: The selected parameters seem to be adequate to characterize clamp
quality. The novel, fully automated clamp device ClampArt achieves high clamp
quality, which in future trials should be compared with other (automated and
manual) clamp methods.
PMID- 25852076
TI - Employment and disability pension after central nervous system infections in
adults.
AB - In this nationwide population-based cohort study using national Danish
registries, in the period 1980-2008, our aim was to study employment and receipt
of disability pension after central nervous system infections. All patients
diagnosed between 20 and 55 years of age with meningococcal (n = 451),
pneumococcal (n = 553), or viral (n = 1,433) meningitis or with herpes simplex
encephalitis (n = 115), who were alive 1 year after diagnosis, were identified.
Comparison cohorts were drawn from the general population, and their members were
individually matched on age and sex to patients. Five years after diagnosis, the
differences in probability of being employed as a former patient with
pneumococcal meningitis or herpes simplex encephalitis versus being a member of
the comparison cohorts were -19.9% (95% confidence interval (CI): -24.7, -15.1)
and -21.1% (95% CI: -33.0, -9.3), respectively, and the corresponding differences
in probability of receiving disability pension were 20.2% (95% CI: 13.7, 26.7)
and 16.2% (95% CI: 6.2, 26.3). The differences in probability of being employed
or receiving disability pension in former meningococcal or viral meningitis
patients versus members of the comparison cohorts were small. In conclusion,
pneumococcal meningitis and herpes simplex encephalitis were associated with
substantially decreased employment and increased need for disability pension.
These associations did not seem to apply to meningococcal meningitis or viral
meningitis.
PMID- 25852077
TI - Obesity and Prostate Cancer Risk According to Tumor TMPRSS2:ERG Gene Fusion
Status.
AB - The T2E gene fusion, formed by fusion of the transmembrane protease, serine 2,
gene (TMPRSS2) with the erythroblast transformation-specific (ETS)-related gene
(ERG), is found in approximately 50% of prostate cancers and may characterize
distinct molecular subtypes of prostate cancer with different etiologies. We
investigated the relationship between body mass index (BMI; weight (kg)/height
(m)(2)) and prostate cancer risk by T2E status. Study participants were residents
of King County, Washington, recruited for 2 population-based case-control studies
conducted in 1993-1996 and 2002-2005. Tumor T2E status was determined for 563
prostate cancer patients who underwent radical prostatectomy. Information on
weight, height, and covariables was obtained through in-person interviews. We
performed polytomous logistic regression to calculate odds ratios and 95%
confidence intervals for T2E-positive and -negative prostate cancer. Comparing
the highest BMI quartile with the lowest, inverse associations were observed
between recent (>=29.7 vs. <24.5: odds ratio = 0.66, 95% confidence interval:
0.45, 0.97) and maximum (>=31.8 vs. <25.9: odds ratio = 0.69, 95% confidence
interval: 0.47, 1.02) BMI and the risk of T2E-positive prostate cancer. No
significant associations were seen for men with T2E-negative tumors. This study
provides evidence that obesity is specifically associated with reduced risk of
developing androgen-responsive T2E fusion-positive tumors. The altered steroid
hormone profile in obese men may contribute to this inverse association.
PMID- 25852078
TI - Reconstructing Past Admixture Processes from Local Genomic Ancestry Using Wavelet
Transformation.
AB - Admixture between long-separated populations is a defining feature of the genomes
of many species. The mosaic block structure of admixed genomes can provide
information about past contact events, including the time and extent of
admixture. Here, we describe an improved wavelet-based technique that better
characterizes ancestry block structure from observed genomic patterns. principal
components analysis is first applied to genomic data to identify the primary
population structure, followed by wavelet decomposition to develop a new
characterization of local ancestry information along the chromosomes. For testing
purposes, this method is applied to human genome-wide genotype data from
Indonesia, as well as virtual genetic data generated using genome-scale
sequential coalescent simulations under a wide range of admixture scenarios. Time
of admixture is inferred using an approximate Bayesian computation framework,
providing robust estimates of both admixture times and their associated levels of
uncertainty. Crucially, we demonstrate that this revised wavelet approach, which
we have released as the R package adwave, provides improved statistical power
over existing wavelet-based techniques and can be used to address a broad range
of admixture questions.
PMID- 25852079
TI - Can Medical Diagnosis Benefit from "Unconscious Thought"?
AB - The unconscious thought theory argues that making complex decisions after a
period of distraction can lead to better decision quality than deciding either
immediately or after conscious deliberation. Two studies have tested this
unconscious thought effect (UTE) in clinical diagnosis with conflicting results.
The studies used different methodologies and had methodological weaknesses. We
attempted to replicate the UTE in medical diagnosis by providing favorable
conditions for the effect while maintaining ecological validity. Family
physicians (N= 116) diagnosed 3 complex cases in 1 of 3 thinking modes:
immediate, unconscious (UT), and conscious (CT). Cases were divided into short
sentences, which were presented briefly and sequentially on computer. After each
case presentation, the immediate response group gave a diagnosis, the UT group
performed a 2-back distraction task for 3 min before giving a diagnosis, and the
CT group could take as long as necessary before giving a diagnosis. We found no
differences in diagnostic accuracy between groups (P= 0.95). The CT group took a
median of 7 s to diagnose, which suggests that physicians were able to diagnose
"online," as information was being presented. The lack of a difference between
the immediate and UT groups suggests that the distraction had no additional
effect on performance. To assess the decisiveness of the evidence of this null
result, we computed a Bayes factor (BF01) for the 2 comparisons of interest. We
found a BF01of 5.76 for the UT versus immediate comparison and of 3.61 for the UT
versus CT comparison. Both BFs provide substantial evidence in favor of the null
hypothesis: physicians' diagnoses made after distraction are no better than
diagnoses made either immediately or after self-paced deliberation.
PMID- 25852080
TI - Empirical Treatment Effectiveness Models for Binary Outcomes.
AB - Randomized trials provide strong evidence regarding efficacy of interventions but
are limited in their capacity to address potential heterogeneity in effectiveness
within broad clinical populations. For example, a treatment that on average is
superior may be distinctly worse in certain patients. We propose a technique for
using large electronic health registries to develop and validate decision models
that measure-for distinct combinations of covariate values-the difference in
predicted outcomes among 2 alternative treatments. We demonstrate the methodology
in a prototype analysis of in-hospital mortality under alternative
revascularization treatments. First, we developed prediction models for a binary
outcome of interest for each treatment. Decision criteria were then defined based
on the treatment-specific model predictions. Patients were then classified as
receiving concordant or discordant care (in relation to the model
recommendation), and the association between discordance and outcomes was
evaluated. We then present alternative decision criteria and validation
methodologies, as well as sensitivity analyses that investigate 1) the imbalance
between treatments on observed covariates and 2) the aggregate impact of
unobserved covariates. Our methodology supplements population-average clinical
trial results by modeling heterogeneity in outcomes according to specific
covariate values. It thus allows for assessment of current practice, from which
cogent hypotheses for improved care can be derived. Newly emerging large
population registries will allow for accurate predictions of outcome risk under
competing treatments, as complex functions of predictor variables. Whether or not
the models might be used to inform decision making depends on the extent to which
important predictors are available. Further work is needed to understand the
strengths and limitations of this approach, particularly in relation to those
based on randomized trials.
PMID- 25852081
TI - In vivo cardiac role of migfilin during experimental pressure overload.
AB - AIMS: Increased myocardial wall strain triggers the cardiac hypertrophic response
by increasing cardiomyocyte size, reprogramming gene expression, and enhancing
contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton
associated protein that was found to translocate in vitro into the nucleus in a
Ca(2+)-dependent manner, where it co-activates the pivotal cardiac transcription
factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and
stress response is unclear. METHODS AND RESULTS: To define the role of migfilin
in cardiac hypertrophy, we induced hypertension by transverse aortic constriction
(TAC) and compared cardiac morphology and function of migfilin knockout (KO) with
wild-type (WT) hearts. Heart size and myocardial contractility were comparable in
untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced
extent of hypertrophic remodelling in response to chronic hypertensile stress.
Migfilin KO mice maintained their cardiac function for a longer time period
compared with WT mice, which presented extensive fibrosis and death due to heart
failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes,
and migfilin KO hearts showed reduced Akt activation during the early response to
pressure overload. CONCLUSIONS: Our findings indicate an important role of
migfilin in the regulation of cardiac hypertrophy upon experimental TAC.
PMID- 25852083
TI - DNA-dependent protein kinase (DNA-PK) permits vascular smooth muscle cell
proliferation through phosphorylation of the orphan nuclear receptor NOR1.
AB - AIMS: Being central part of the DNA repair machinery, DNA-dependent protein
kinase (DNA-PK) seems to be involved in other signalling processes, as well. NOR1
is a member of the NR4A subfamily of nuclear receptors, which plays a central
role in vascular smooth muscle cell (SMC) proliferation and in vascular
proliferative processes. We determined putative phosphorylation sites of NDA-PK
in NOR1 and hypothesized that the enzyme is able to modulate NOR1 signalling and,
this way, proliferation of SMC. METHODS AND RESULTS: Cultured human aortic SMC
were treated with the specific DNA-PK inhibitor NU7026 (or siRNA), which resulted
in a 70% inhibition of FCS-induced proliferation as measured by BrdU
incorporation. Furthermore, FCS-stimulated up-regulation of NOR1 protein as well
as the cell-cycle promoting proteins proliferating cell nuclear antigen (PCNA),
cyclin D1, and hyperphosphorylation of the retinoblastoma protein were prevented
by DNA-PK inhibition. Co-immunoprecipitation studies from VSM cell lysates
demonstrated that DNA-PK forms a complex with NOR1. Mutational analysis and
kinase assays demonstrated that NOR1 is a substrate of DNA-PK and is
phosphorylated in the N-terminal domain. Phosphorylation resulted in post
transcriptional stabilization of the protein through prevention of its
ubiquitination. Active DNA-PK and NOR1 were found predominantly expressed within
the neointima of human atherosclerotic tissue specimens. In mice, inhibition of
DNA-PK significantly attenuated neointimal lesion size 3 weeks after wire-injury.
CONCLUSION: DNA-PK directly phosphorylates NOR-1 and, this way, modulates SMC
proliferation. These data add to our understanding of vascular remodelling
processes and opens new avenues for treatment of vascular proliferative diseases.
PMID- 25852082
TI - A novel human R25C-phospholamban mutation is associated with super-inhibition of
calcium cycling and ventricular arrhythmia.
AB - AIMS: Depressed sarcoplasmic reticulum (SR) Ca(2+) cycling, a universal
characteristic of human and experimental heart failure, may be associated with
genetic alterations in key Ca(2+)-handling proteins. In this study, we identified
a novel PLN mutation (R25C) in dilated cardiomyopathy (DCM) and investigated its
functional significance in cardiomyocyte Ca(2+)-handling and contractility.
METHODS AND RESULTS: Exome sequencing identified a C73T substitution in the
coding region of PLN in a family with DCM. The four heterozygous family members
had implantable cardiac defibrillators, and three developed prominent ventricular
arrhythmias. Overexpression of R25C-PLN in adult rat cardiomyocytes significantly
suppressed the Ca(2+) affinity of SR Ca(2+)-ATPase (SERCA2a), resulting in
decreased SR Ca(2+) content, Ca(2+) transients, and impaired contractile
function, compared with WT-PLN. These inhibitory effects were associated with
enhanced interaction of R25C-PLN with SERCA2, which was prevented by PKA
phosphorylation. Accordingly, isoproterenol stimulation relieved the depressive
effects of R25C-PLN in cardiomyocytes. However, R25C-PLN also elicited increases
in the frequency of Ca(2+) sparks and waves as well as stress-induced
aftercontractions. This was accompanied by increased Ca(2+)/calmodulin-dependent
protein kinase II activity and hyper-phosphorylation of RyR2 at serine 2814.
CONCLUSION: The findings demonstrate that human R25C-PLN is associated with super
inhibition of SERCA2a and Ca(2+) transport as well as increased SR Ca(2+) leak,
promoting arrhythmogenesis under stress conditions. This is the first mechanistic
evidence that increased PLN inhibition may impact both SR Ca(2+) uptake and
Ca(2+) release activities and suggests that the human R25C-PLN may be a
prognostic factor for increased ventricular arrhythmia risk in DCM carriers.
PMID- 25852084
TI - Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired
nitric oxide signalling.
AB - AIMS: Lymphatic vessel dysfunction is an emerging component of metabolic diseases
and can lead to tissue lipid accumulation, dyslipidaemia, and oedema. While lymph
leakage has been implicated in obesity and hypercholesterolaemia, whether similar
lymphatic dysfunction exists in diabetes has not been investigated. METHODS AND
RESULTS: To measure the lymphatic integrity of transgenic mice, we developed a
new assay that quantifies the solute permeability of murine collecting lymphatic
vessels. Compared with age-matched wild-type (WT) controls, the permeability of
collecting lymphatics from diabetic, leptin receptor-deficient (db/db) mice was
elevated >130-fold. Augmenting nitric oxide (NO) production by suffusion of l
arginine rescued this defect. Using pharmacological tools and eNOS(-/-) mice, we
found that NO increased WT lymphatic permeability, but reduced db/db lymphatic
permeability. These conflicting actions of NO were reconciled by the finding that
phosphodiesterase 3 (PDE3), normally inhibited by NO signalling, was active in
db/db lymphatics and inhibition of this enzyme restored barrier function.
CONCLUSION: In conclusion, we identified the first lymphatic vascular defect in
type 2 diabetes, an enhanced permeability caused by low NO bioavailability.
Further, this demonstrates that PDE3 inhibition is required to maintain lymphatic
vessel integrity and represents a viable therapeutic target for lymphatic
endothelial dysfunction in metabolic disease.
PMID- 25852086
TI - UK death rates in children's heart surgery have almost halved over past decade.
PMID- 25852085
TI - Inhibition of type 5 phosphodiesterase counteracts beta2-adrenergic signalling in
beating cardiomyocytes.
AB - AIMS: Compartmentalization of cAMP and PKA activity in cardiac muscle cells plays
a key role in maintaining basal and enhanced contractility stimulated by
sympathetic nerve activity. In cardiomyocytes, activation of adrenergic receptor
increases cAMP production, which is countered by the hydrolytic activity of
selective phosphodiesterases (PDEs). The intracellular regional dynamics of cAMP
production and hydrolysis modulate downstream signals resulting in different
biological responses. The interplay between beta receptors (betaARs) signalling
and phosphodiesterase 5 (PDE5) activity remains to be addressed. METHODS AND
RESULTS: Using combined strategies with pharmacological inhibitors and genetic
deletion of PDEs and betaAR isoforms, we revealed a specific pool of cAMP that is
under dual regulation by PDE2 and, indirectly, PDE5 activity. Inhibition of PDE5
with sildenafil produces a cGMP-dependent activation of PDE2 that attenuates cAMP
generation induced by betaAR agonists, with concomitant modulation of stimulated
contraction rate and calcium transients. PDE2 haploinsufficiency abolished the
effects of sildenafil. The negative chronotropic effect of PDE5 inhibition
through PDE2 activation was also observed in sinoatrial node tissue from adult
mice. PDE5 inhibition selectively lowered contraction rate stimulated by beta2AR,
but not beta1AR activation, supporting a compartmentalization of the cGMP
modulated pool of cAMP. CONCLUSION: These data identify a new effect of PDE5
inhibitors on the modulation of cardiomyocyte response to adrenergic stimulation
via PDE5-PDE2-mediated cross-talk.
PMID- 25852087
TI - Drought-induced tree mortality: from discrete observations to comprehensive
research.
PMID- 25852088
TI - Is nitrous oxide a genotoxic carcinogen?
AB - Nitrous oxide (N2O) has been widely used as a dental and surgical anaesthetic for
over 150 years. However, results from a recent study suggested that increased DNA
damage was seen in lymphocytes from surgical patients and this led to its
continued clinical use to be questioned. The data can be challenged on technical
grounds and must be considered with other studies in order to assess any possible
risk. There are other studies indicating that N2O has weak genotoxicity in man,
but these are confused by exposure of the populations to other anaesthetic gases
including isoflurane and sevoflurane, both of which have also been reported to
increase DNA damage. It should be noted that the suggested genotoxic mechanisms
are all indirect, including folate deficiency, oxidative stress and homocysteine
toxicity. Further, results from in vitro studies indicate that N2O has no direct
DNA reactivity as negative results were obtained in a bacterial mutation (Ames)
test and an assay for mutation at the hprt locus in Chinese hamster lung cells.
Although not performed to definitive study designs, no evidence of
carcinogenicity was seen in two long-term tests in mice and another in rats.
Although there is some evidence that N2O is weakly genotoxic in humans, this
appears to be similar to that reported for isoflurane and sevoflurane and all the
postulated mechanisms have clear thresholds with no evidence of direct DNA
reactivity. Because any potential genotoxic mechanism would have a threshold, it
seems reasonable to conclude that neither occasional high exposure to patients as
an anaesthetic nor low-level exposure to staff within published recommended
exposure limits presents any significant carcinogenic risk.
PMID- 25852089
TI - Pityriasis versicolor.
PMID- 25852090
TI - CCR4+ Regulatory T Cells Accumulate in the Very Elderly and Correlate With
Superior 8-Year Survival.
AB - CD4(+) regulatory T cells (Tregs) are a distinct population of T cells involved
in maintaining peripheral tolerance to self-antigens. Several studies have shown
increased frequency and number of Tregs in the elderly. Whether such an increase
has any clinical relevance has not been addressed. Here, we have analyzed
circulating Tregs in 114 donors between the ages of 18 and 89 years and assessed
their implications for survival of the very elderly. In line with previously
published data, we observed higher proportions of Tregs in the elderly.
Expression of chemokine receptor 4 (CCR4) by Tregs has been shown to characterize
antigen-primed activated Tregs with immediate suppressive function. Thus we
further analyzed Tregs expressing or lacking this chemokine receptor. There were
more CCR4(+) and CCR4(-) Tregs in the elderly than the young. Finally, using a
subset of 48 elderly donors participating in the Leiden 85-plus study we
documented that people with greater median frequencies of CCR4(+) Tregs enjoyed a
better 8-year survival rate than those with lower frequencies of these cells. Our
data, demonstrating for the first time a positive correlation between increased
frequency of Tregs and survival in the elderly, imply an increasing importance of
controlling inappropriate immune responses and inflammation as we grew old.
PMID- 25852091
TI - Cancer in a gerontological context.
PMID- 25852092
TI - Prevalence of abuse in mentally ill patients visiting outpatient setting in a
tertiary care hospital in India.
AB - AIM: In a developing country such as India, the abuse of patients suffering from
psychiatric disorders has been underreported. The aim of this study was to detect
abuse in chronically ill psychiatric patients visiting a psychiatric outpatient
setting in a tertiary care hospital in Delhi, India. MATERIAL AND METHODS: A
cross-sectional descriptive written survey was carried out on 406 patients. A
self-administered questionnaire for patient abuse was developed in Hindi based on
the World Health Organization's Domestic Violence Questionnaire that encompassed
questions regarding physical, emotional and sexual abuse. RESULTS: Of the 406
patients, 294 (72%) suffered from abuse, with 64% experiencing emotional abuse,
39% physical abuse and 21% sexual abuse. In chronically ill psychiatric patients,
a significant association was found between education and abuse, with most abuse
occurring among senior secondary pass outs (i.e. 11-12 years of education) and
least among junior high school pass outs (6-8 years of education). A majority
(74%) of these patients lived in urban areas (p = .020). A significant
association was also found between abuse and the psychiatric diagnosis of the
patient, with 53% suffering from depression, 66% anxiety disorder, 81% bipolar
disorder, 94% psychotic disorder, 86% obsessive compulsive disorder, 44% sexual
disorder and 12% other psychiatric disorders. CONCLUSIONS: There is a need to
create awareness in society in order to prevent abuse. Screening for abuse in
routine psychiatric practice is of utmost importance so that timely interventions
can be given, thereby preventing its deleterious health consequences.
PMID- 25852093
TI - Benefit of STR-based chimerism analysis to identify TA-GVHD as a cause of death:
Utility of various biological specimens.
AB - Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare condition.
It can occur after blood transfusion in immune-compromised and occasionally even
in immune-competent patients, and is associated with a mortality rate of >90%.
The diagnosis of TA-GVHD is often delayed because of its non-specific clinical
features. A case of an immune-competent child who developed TA-GVHD is reported
here. DNA profiling (short tandem repeat analysis), a technique that has a wide
application in forensic medicine, was performed to detect the presence of donor
cells in this patient. The findings suggest that more studies are needed with
this tool, and the diagnostic potential of using other multiple biological
specimens for DNA profiling such as the hair follicle and buccal swab should be
evaluated. This is the first case report where the donor's DNA fingerprinting
pattern was substantiated from a patient's hair follicle sample. Chimerism was
also present in the blood and buccal swab specimens.
PMID- 25852094
TI - Health Research Symposium 2014: translating health research into policy for
health of the population.
PMID- 25852095
TI - Stigma towards people with psychiatric disorders.
PMID- 25852096
TI - Epidemiology and natural history of depressive disorders in primary care.
PMID- 25852097
TI - Early intervention versus standard care for psychosis in Hong Kong: a 10-year
study.
PMID- 25852098
TI - Three-year community case management for early psychosis: a randomised controlled
study.
PMID- 25852099
TI - Perceived stigmatisation of patients with mental illness and its psychosocial
correlates: a prospective cohort study.
PMID- 25852100
TI - Health outcomes, community resources for health, and support strategies 12 months
after discharge in patients with severe mental illness.
PMID- 25852101
TI - Assertive community treatment for psychiatric patients with frequent
hospitalisation.
PMID- 25852102
TI - Pathway of psychiatric care in Hong Kong.
PMID- 25852103
TI - Use of the Historical, Clinical, Risk Management-20 to assess the risk of
violence by discharged psychiatric patients.
PMID- 25852105
TI - A curious case of facial swelling in the night-time.
PMID- 25852104
TI - RBM7 subunit of the NEXT complex binds U-rich sequences and targets 3'-end
extended forms of snRNAs.
AB - The Nuclear Exosome Targeting (NEXT) complex is a key cofactor of the mammalian
nuclear exosome in the removal of Promoter Upstream Transcripts (PROMPTs) and
potentially aberrant forms of other noncoding RNAs, such as snRNAs. NEXT is
composed of three subunits SKIV2L2, ZCCHC8 and RBM7. We have recently identified
the NEXT complex in our screen for oligo(U) RNA-binding factors. Here, we
demonstrate that NEXT displays preference for U-rich pyrimidine sequences and
this RNA binding is mediated by the RNA recognition motif (RRM) of the RBM7
subunit. We solved the structure of RBM7 RRM and identified two phenylalanine
residues that are critical for interaction with RNA. Furthermore, we showed that
these residues are required for the NEXT interaction with snRNAs in vivo.
Finally, we show that depletion of components of the NEXT complex alone or
together with exosome nucleases resulted in the accumulation of mature as well as
extended forms of snRNAs. Thus, our data suggest a new scenario in which the NEXT
complex is involved in the surveillance of snRNAs and/or biogenesis of snRNPs.
PMID- 25852106
TI - Stress and Negative Relationship Quality among Older Couples: Implications for
Blood Pressure.
AB - OBJECTIVES: The cardiovascular system may represent a significant pathway by
which marriage and stress influence health, but research has focused on married
individuals cross-sectionally. This study examined associations among chronic
stress, negative spousal relationship quality, and systolic blood pressure over
time among middle-aged and older husbands and wives. METHOD: Participants were
from the nationally representative longitudinal Health and Retirement Study. A
total of 1,356 (N = 2,712) married and cohabitating couples completed
psychosocial and biomeasure assessments in waves 2006 and 2010. Analyses examined
whether Wave 1 (2006) relationship quality and stress were associated with
changes in blood pressure over time. RESULTS: The effects of stress and negative
relationship quality were dyadic and varied by gender. Husbands had increased
blood pressure when wives reported greater stress, and this link was exacerbated
by negative spousal relationship quality. Negative relationship quality predicted
increased blood pressure when both members of the couple reported negative
quality relations. DISCUSSION: Findings support the dyadic biopsychosocial model
of marriage and health indicating: (a) stress and relationship quality directly
effect the cardiovascular system, (b) relationship quality moderates the effect
of stress, and (c) the dyad rather than only the individual should be considered
when examining marriage and health.
PMID- 25852107
TI - Paradoxical effect of capecitabine in 5-fluorouracil-induced cardiotoxicity: A
case vignette and literature review.
AB - 5-fluorouracil is a chemotherapeutic agent that plays an important role in the
treatment of various cancers including head and neck and gastrointestinal
malignancies. Therapy with 5-fluorouracil is rarely associated with cardiotoxic
effects including angina, heart failure, myocardial infarction and cardiac
arrest, resulting in discontinuation at the expense of sub-optimal treatment of
the targeted malignancy. In this article, we review the literature reported on 5
fluorouracil-associated cardiotoxicity and present a case of a patient who
experienced chest pain on 5-fluorouracil. The cardiac symptoms subsided after
initiation of capecitabine, the oral formulation of 5-fluorouracil. To our
knowledge, this is only the second reported case where 5-fluorouracil was
successfully replaced by capecitabine without recurrence of cardiac symptoms.
Capecitabine may be a viable option for patients who develop 5-fluorouracil
induced chest pain. However, large clinical trials are warranted to confirm these
findings. Currently, there is insufficient evidence to recommend an optimal
approach for safe and effective alternative treatment for patients who experience
5-fluorouracil-induced cardiac adverse events.
PMID- 25852108
TI - Ultrasound for internists: changing bedside examination.
PMID- 25852109
TI - Lung ultrasound: routine practice for the next generation of internists.
AB - BACKGROUND: The lung is at the crossroads of ventilation and circulation and can
provide a wealth of diagnostic information. In the past, lung ultrasound (LUS)
was considered impossible. However, the interplay between air, fluid and pleurae
creates distinctive artefacts. Combinations of these artefacts can help
differentiate between various pathological processes, including pulmonary oedema,
pneumonia, pulmonary embolism, obstructive airway disease and pneumothorax. LUS,
when used by experienced physicians, is superior to chest X-ray and comparable to
computed tomography for establishing a diagnosis in acutely dyspnoeic patients.
LUS allows for rapid, non-invasive and bedside patient assessment. It is
therefore unfortunate that unlike many other medical specialists in the
Netherlands, internists have not yet incorporated LUS into their daily practice.
OBJECTIVES: This review aims to be the starting point for internists wanting to
acquire competence in LUS. REVIEW CONTENT: This narrative review describes the
principles of ultrasound equipment, LUS artefacts, gives practical guidance to
perform LUS and provides a road map towards LUS competence. Furthermore, it
presents a decision tree to differentiate between causes of acute dyspnoea.
AUTHORS CONCLUSIONS: LUS is a promising diagnostic technique that can be of great
help for the internist. It can be applied directly at the bedside and can also be
used to follow up on disease progression and therapy. It is our belief that it
will replace the stethoscope and that it will be the most used imaging technique
in the near future, especially in dyspnoeic patients.
PMID- 25852110
TI - Hepcidin in chronic kidney disease: not an anaemia management tool, but promising
as a cardiovascular biomarker.
AB - Hepcidin is a key regulator of iron homeostasis and plays a role in the
pathogenesis of anaemia of chronic disease. Its levels are increased in patients
with chronic kidney disease (CKD) due to diminished renal clearance and an
inflammatory state. Increased hepcidin levels in CKD patients are supposed to be
responsible for functional iron deficiency in these patients and contribute to
renal anaemia and resistance to erythropoiesis-stimulating agents. Therefore,
hepcidin was purported to be useful as a management tool guiding treatment of
renal anaemia. Furthermore, since hepcidin is associated with iron accumulation
in macrophages in the vessel wall inducing oxidative stress and atherosclerosis,
it has been speculated that hepcidin might function as a biomarker of
cardiovascular disease. In this descriptive review, the merits of hepcidin with
respect to its role in the pathophysiology of renal anaemia in CKD patients, its
presumptive role as a practical diagnostic tool guiding management of renal
anaemia, and its possible usefulness as a prognostic biomarker will be discussed.
PMID- 25852111
TI - The standardised mortality ratio: the proper quality indicator in acute
leukaemia?
AB - BACKGROUND: The standardised mortality ratio (SMR) is a quality indicator used to
measure quality of care in the Netherlands. It is subject to much criticism,
which was the reason to study the value of the SMR as a quality indicator for the
treatment of acute leukaemia. METHODS: A retrospective analysis was performed in
patients with acute leukaemia admitted to a Santeon hospital during the period
2005-2009. SMR values were calculated and compared with the overall survival
(OS). RESULTS: During the study period, 455 unique patients were admitted with
acute leukaemia. SMR calculation was based on 992 admissions. SMR analysis
yielded a high mortality ratio in hospital 1, 2, 3 and 4 in comparison with the
national average (100), significant for hospital 1 and 4 (180 [CI 95% 126-257]
and 187 [CI 95% 134-261], respectively) OS analysis also showed a significantly
different outcome between hospitals. However, using OS as outcome parameter,
hospital 2 and 6 showed the lowest performance as compared with hospital 1 and 4
using SMR as parameter. After multivariate analysis, age (HR 1.04; CI 95% 1.03
1.05; p < 0.001) and hospital (hospital 5 compared with 6: HR 0.54; CI 95% 0.30-
.98; p = 0.043; hospital 2 compared with 1: HR 1.51; CI 95% 1.02-2.23; p = 0.039)
were the only significant variables that influenced OS. CONCLUSION: Outcome
according to SMR is not equivalent to outcome according to OS. This study shows
that the use of the SMR as a quality indicator for the treatment of acute
leukaemia does not appear to be justified.
PMID- 25852112
TI - Prevalence and correction of severe hypovitaminosis D in patients over 50 years
with a low-energy fracture.
AB - PURPOSE/INTRODUCTION: To examine the increase in serum 25(OH) vitamin D levels
after supplementation with 800 IU/day of vitamin D in patients with low vitamin D
levels and which factors affected the increase in vitamin D levels. METHODS: The
study included patients > 50 years with a low-energy fracture and a vitamin D
level < 30 nmol/l. This was a retrospective study and was carried out at a large
non-teaching hospital in the Netherlands. RESULTS: 82 patients were included,
mean basal 25(OH) vitamin D level was 21.2 nmol/l. After a mean of 9.8 weeks, the
mean increase in vitamin D was 48.5 nmol/l. Only 45.1% reached the target level
of > 50 nmol/l. The increase was correlated with the basal level of vitamin D (p
< 0.05), and the time interval between the two vitamin D measurements (p < 0.05)
and was inversely related to body weight (p < 0.05), but was not related to age,
gender or renal function. CONCLUSIONS: We found that the generally recommended
dosage of 800 IU of vitamin D per day resulted in suboptimal serum levels after
ten weeks of treatment in more than half of the patients. The increase in vitamin
D levels was higher in patients with low body weight and in patients with very
low basal vitamin D levels. These data suggest that these patients should
initially be treated with higher dosages of vitamin D. If not possible, vitamin D
measurements should be performed after at least six months of supplementation
with dosage adjustment.
PMID- 25852113
TI - Hypercholesterolaemia and hepatosplenomegaly: two manifestations of cholesteryl
ester storage disease.
AB - Cholesteryl ester storage disease (CESD) is a rare autosomal recessive disease
caused by mutations in LIPA. Here we describe two different clinical
presentations of this disease: one case with a clear phenotype of familial
hypercholesterolaemia and one case with hepatosplenomegaly from childhood
onwards. These two cases exemplify the diversity of clinical phenotypes of
patients with CESD. Knowledge on the phenotypic variability of the disease is of
clinical relevance in light of enzyme replacement therapy (sebelipase alpha) for
patients with mutations in LIPA, which is currently under development.
PMID- 25852114
TI - Life-threatening acute lung injury after gamma butyrolactone ingestion.
AB - We describe a case of a 44-year-old woman with a borderline personality disorder
and chronic gamma- butyrolactone (GBL) use who presented with progressive
dyspnoea and an altered mental status. A high anion gap metabolic acidosis and
acute lung injury was diagnosed. We hypothesise this was caused by GBL. In this
case report we describe the diagnostic process and possible pathophysiological
mechanisms that may have led to this life-threatening condition.
PMID- 25852115
TI - Ticagrelor-induced renal failure leading to statin-induced rhabdomyolysis.
AB - Renal function deterioration is a rather frequent side effect of ticagrelor; this
is especially so in patients over the age of 75, with pre-existent mild renal
failure and/or taking an angiotensin receptor inhibitor. We describe a patient in
whom deterioration of renal function due to ticagrelor led to a rise in serum
concentration of rosuvastatin which resulted in rhabdomyolysis. The presented
case emphasises the importance to check renal function routinely before and one
month after starting ticagrelor and to screen carefully for possible interactions
with other drugs.
PMID- 25852116
TI - An immunocompromised woman with a lung tumour.
PMID- 25852117
TI - Intermittent abdominal pain and melaena in a 64-year-old man.
PMID- 25852118
TI - Should we put pressure on using lower levels of PEEP in patients without ARDS in
The Netherlands?
PMID- 25852119
TI - Investigation that may have contributed to GP's suicide was carried out
correctly, report says.
PMID- 25852120
TI - Quantitative Assessment of Multiorgan Sequestration of Parasites in Fatal
Pediatric Cerebral Malaria.
AB - Children in sub-Saharan Africa continue to acquire and die from cerebral malaria,
despite efforts to control or eliminate the causative agent, Plasmodium
falciparum. We present a quantitative histopathological assessment of the
sequestration of parasitized erythrocytes in multiple organs obtained during a
prospective series of 103 autopsies performed between 1996 and 2010 in Blantyre,
Malawi, on pediatric patients who died from cerebral malaria and controls. After
the brain, sequestration of parasites was most intense in the gastrointestinal
tract, both in patients with cerebral malaria and those with parasitemia in other
organs. Within cases of histologically defined cerebral malaria, which includes
phenotypes termed "sequestration only" (CM1) and "sequestration with
extravascular pathology" (CM2), CM1 was associated with large parasite numbers in
the spleen and CM2 with intense parasite sequestration in the skin. A striking
histological finding overall was the marked sequestration of parasitized
erythrocytes across most organs in patients with fatal cerebral malaria,
supporting the hypothesis that the disease is, in part, a result of a high level
of total-body parasite sequestration.
PMID- 25852121
TI - Des agents de sante communautaires pour la promotion de la sante des pasteurs
nomades au Mali.
AB - Au Mali, les nomades (des Maures, Touaregs et Peulhs) representent environ 1,25
million de personnes. Les services de sante leur sont peu accessibles en raison
de leur mobilite, liee a leur activite d'elevage. La question que se posent
plusieurs intervenants en sante publique des pays ou vivent ces nomades est de
savoir comment ameliorer leur sante. Dans ce commentaire, apres un bref expose
des problemes lies a l'acces aux services de sante, nous proposons une approche
innovante et holistique de la sante, qui soutient que des agents de sante
communautaires (ASC) pourraient contribuer a ameliorer la sante des nomades en
offrant conjointement des services de sante aux nomades et a leurs animaux (le
concept " One Health " [d'Une Seule Sante]). Des pistes de reflexion sont
degagees, quant aux principaux defis pour leur efficacite et durabilite, qui sont
la conception et gestion du programme, leur soutien par les communautes et leur
integration aux services de sante publique et veterinaire.
PMID- 25852123
TI - Editorial commentary: what constitutes appropriate treatment of post-Lyme disease
symptoms and other pain and fatigue syndromes?
PMID- 25852124
TI - Unorthodox alternative therapies marketed to treat Lyme disease.
AB - BACKGROUND: Some patients with medically unexplained symptoms or alternative
medical diagnoses suspect that they chronically suffer from the tick-borne
infection Lyme disease. These patients are commonly targeted by providers of
alternative therapies. This study was designed to identify and characterize the
range of unorthodox alternative therapies advertised to patients with a diagnosis
of Lyme disease. METHODS: Internet searches using the Google search engine were
performed to identify the websites of clinics and services that marketed
nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed
search engine to identify any scientific studies evaluating such treatments for
Lyme disease. Websites were included in our review so long as they advertised a
commercial, nonantimicrobial product or service that specifically mentioned
utility for Lyme disease. Websites with patient testimonials (such as discussion
groups) were excluded unless the testimonial appeared as marketing on a
commercial site. RESULTS: More than 30 alternative treatments were identified,
which fell into several broad categories: these included oxygen and reactive
oxygen therapy; energy and radiation-based therapies; nutritional therapy;
chelation and heavy metal therapy; and biological and pharmacological therapies
ranging from certain medications without recognized therapeutic effects on
Borrelia burgdorgeri to stem cell transplantation. Review of the medical
literature did not substantiate efficacy or, in most cases, any rationale for the
advertised treatments. CONCLUSIONS: Providers of alternative therapies commonly
target patients who believe they have Lyme disease. The efficacy of these
unconventional treatments for Lyme disease is not supported by scientific
evidence, and in many cases they are potentially harmful.
PMID- 25852125
TI - Low risk of lamivudine-resistant HBV and hepatic flares in treated HIV-HBV
coinfected patients from Cote d'Ivoire.
AB - BACKGROUND: In HIV-HBV-coinfected patients from sub-Saharan Africa, incidence of
antiviral resistant HBV-mutations after initiating long-term antiretroviral
therapy (ART) has only been evaluated in limited patient populations. METHODS: In
this nested, prospective cohort study from two randomized controlled trials in
Cote d'Ivoire, 168 ART-naive HIV-HBV-coinfected patients, starting lamivudine
(LAM, n=82) or tenofovir/emtricitabine (TDF/FTC, n=86) containing ART were
included. HBV DNA viral load (VL) was quantified using an in-house assay
(detection limit: <12 copies/ml) while pol and preS/S regions of positive samples
were sequenced. RESULTS: At ART-initiation, 39 (23.2%) were hepatitis B e antigen
positive, 53 (31.5%) had alanine or aspartate aminotransferase levels >40 IU/ml
and 98/100 (98.0%) harboured genotype E. Among the 127 (75.6%) patients with
detectable baseline HBV VL (median 4.27 log10 copies/ml, IQR 3.14-7.64),
cumulative percentage achieving undetectable HBV DNA was 74.2% for patients
undergoing LAM-containing ART and 94.2% for TDF/FTC-containing ART after a median
35.5 months (IQR 24.3-36.5). No baseline antiviral resistance mutations were
observed. Among 28/127 (22.1%) patients with low-level persistent viraemia (last
HBV VL: between 12 to <10(5) copies/ml), no incident amino acid changes
associated with antiviral resistance were observed. Among 11/127 (8.7%) patients
with high-level persistent viraemia (last HBV VL: >=10(5) copies/ml), only two
harboured incident LAM-resistance mutations at positions rtV173L+rtL180M+rtM204V
with no patient exhibiting TDF/FTC-resistance. Two patients had transaminase
flares >120 IU/ml (incidence rate =0.5/100 person-years). CONCLUSIONS: Antiviral
resistance, particularly to LAM, was remarkably rare in this cohort of HIV-HBV
coinfected patients. Further research is needed to determine which coinfected
populations might benefit from LAM-containing ART with low risk of resistance.
PMID- 25852127
TI - Lipoprotein (a) upregulates ABCA1 in liver cells via scavenger receptor-B1
through its oxidized phospholipids.
AB - Elevated levels of lipoprotein (a) [Lp(a)] are a well-established risk factor for
developing CVD. While Lp(a) levels are thought to be independent of other plasma
lipoproteins, some trials have reported a positive association between Lp(a) and
HDL. Whether Lp(a) has a direct effect on HDL is not known. Here we investigated
to determine whether Lp(a) had any effect on the ABCA1 pathway of HDL production
in liver cells. Incubation of HepG2 cells with Lp(a) upregulated the PPARgamma
protein by 1.7-fold and the liver X receptor alpha protein by 3-fold. This was
accompanied by a 1.8-fold increase in ABCA1 protein and a 1.5-fold increase in
cholesterol efflux onto apoA1. We showed that Lp(a) was internalized by HepG2
cells, however, the ABCA1 response to Lp(a) was mediated by the selective uptake
of oxidized phospholipids (oxPLs) from Lp(a) via the scavenger receptor-B1 and
not by Lp(a) internalization per se. We conclude that there is a biological
connection between Lp(a) and HDL through the ability of Lp(a)'s oxPLs to
upregulate HDL biosynthesis.
PMID- 25852128
TI - Environmental Risk Factors for Developing Catheter-Related Bloodstream Infection
in Home Parenteral Nutrition Patients: A 6-Year Follow-up Study.
AB - BACKGROUND: Tunneled, cuffed, central venous catheters, including Hickman
catheters and peripherally inserted central venous catheters (PICCs), are the
most commonly used venous access for home parenteral nutrition (HPN) therapy.
Catheter-related bloodstream infection is the most prevalent and severe
complication. This study investigated whether environmental risk factors,
including smoking, catheter management by a home care nurse, colectomy with
stoma, number of infusion days per week, and C-reactive protein at catheter
insertion day, influenced the time to first catheter-related bloodstream
infection (CRBSI). MATERIALS AND METHODS: In this 6-year (2008-2014)
observational cohort study, adult patients with intestinal failure receiving HPN
through either Hickman catheters or PICCs were included. Data were obtained by
reviewing medical records, and the environmental risk factors were analyzed with
the Cox proportional hazards model. RESULTS: A total of 295 catheters (Hickman
catheters: n = 169 and PICCs: n = 126) inserted into 136 patients were
registered. Using the PICCs, 1 additional infusion day per week showed to
significantly decrease the time to first CRBSI by a factor of 2.47. Hickman
catheters managed by a home care nurse had a significantly increased mean (SD)
incidence of CRBSI of 1.45 (0.68) per 1000 catheter days. Hickman catheters not
managed by a home care nurse had a mean (SD) incidence of 0.56 (0.24).
CONCLUSION: Using the PICC, 1 additional infusion day per week decreased the time
to first CRBSI, while having the Hickman catheter managed by a home care nurse
increased the mean CRBSI incidence. No other risk factors were found.
PMID- 25852130
TI - Evidence for iron deficiency screening "inadequate," US panel concludes.
PMID- 25852129
TI - Effect of left ventricular ejection fraction on postoperative outcome in patients
with severe aortic stenosis undergoing aortic valve replacement.
AB - BACKGROUND: In asymptomatic patients with severe aortic stenosis, guidelines
recommend left ventricular ejection fraction (LVEF) of <50% as the threshold for
referral for aortic valve replacement. We investigated the importance of LVEF on
long-term outcome after aortic valve replacement in symptomatic and asymptomatic
patients with severe aortic stenosis. METHODS AND RESULTS: We retrospectively
identified 2017 patients with severe aortic stenosis (aortic valve area<1 cm(2),
mean gradient>=40 mm Hg, or indexed aortic valve area<0.6 cm(2)/m(2)) who
underwent surgical aortic valve replacement from January 1995 to June 2009.
Patients were divided into 4 groups depending on preoperative LVEF (<50% in 300
[15%] patients, 50%-59% in 331 [17%], 60%-69% in 908 [45%], and >=70% in 478
[24%]). During follow-up of 5.3+/-4.4 years, 1056 (52%) patients died. A decrease
in mortality was observed with increasing LVEF, P<0.0001; 5-year mortality
estimates (95% confidence interval) were 0.41 (0.35-0.47), LVEF<50%; 0.35 (0.29
0.41), LVEF 50% to 59%; 0.26 (0.23-0.29), LVEF 60% to 69%; and 0.22 (0.18-0.26),
LVEF>=70%. Compared with patients with LVEF>=60%, patients with LVEF 50% to 59%
had increased mortality (hazard ratio [HR], 1.58; P<0.001), with similar risk
increase in both symptomatic (HR, 1.56; P<0.001) and asymptomatic patients (HR,
1.58; P=0.006). Correcting for risk factors, LV mass index, aortic valve area,
and stroke volume index, LVEF was independently predictive of mortality (HR, 0.88
per 10%; P<0.001). When this analysis was repeated in the subset of 1333 patients
without history of coronary artery disease, LVEF remained associated with
mortality (HR, 0.90 per 10%; P=0.009). CONCLUSIONS: LVEF is a powerful predictor
of outcome in patients with severe aortic stenosis undergoing aortic valve
replacement, independent of the presence of valve-related symptoms.
PMID- 25852132
TI - The pilot, depression, and the salacious headlines that feed stigma.
PMID- 25852131
TI - Potential role of electrostimulation in augmentation of venous blood flow after
total knee replacement: A pilot study.
AB - AIM: To investigate the potential role of a novel electrostimulation device in
augmenting the femoral vein venous blood flow following total knee replacement
surgery. MATERIAL AND METHODS: A total of 30 consecutive patients undergoing
total knee replacement were allocated to receive either peroneal nerve
electrostimulation plus low molecular weight heparin and below-knee compression
stockings (Group 1, electrostimulation group, n = 15, mean age: 63.40 +/- 5.91
years, male: female ratio 9:6) or low molecular weight heparin and below-knee
compression stockings alone (Group 2, control group, n = 15, mean age: 63.86 +/-
7.47 years, male: female ratio 8:7). Electrostimulation was performed for 1 h in
every 4 h after the operation. Peak blood velocity in the femoral vein was
evaluated with Duplex ultrasonongraphy in supine position. Presence of leg edema
and calf diameter was also taken into consideration as outcome measures, which
were recorded both before surgery and at the time of discharge from hospital.
RESULTS: Postoperative peak blood flow velocity in the femoral vein was
significantly higher in electrostimulation group compared to control group (17.46
+/- 2.86 cm/s vs. 13.84 +/- 3.58 cm/s, p < 0.02). Electrostimulation group
achieved a significant increase in peak blood flow velocity in the femoral vein
after the operation (mean increase 67.48 +/- 17.38%, p < 0.001). CONCLUSION:
Electrostimulation of the common peroneal nerve enhanced venous flow in the lower
limb and may potentially be of use as a supplementary technique in deep venous
prophylaxis following lower limb orthopedic operations.
PMID- 25852133
TI - Cardiovascular effects of dipeptidyl peptidase-4 inhibitors in patients with type
2 diabetes.
AB - Cardiovascular (CV) disease is the leading cause of mortality and morbidity in
patients with type 2 diabetes mellitus (T2DM). However, improving glycaemic
control alone has not decreased CV events. Therapies that improve glycaemic
control, CV disease risk factors and CV function are more likely to be
successful. Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent breakdown of
incretin hormones glucagon-like peptide-1(GLP-1) and glucose-dependent
insulinotropic peptide and improve glycaemic control in patients with T2DM. DPP-4
acts on other substrates, many associated with cardioprotection. Thus, inhibition
of DPP-4 may lead to elevations in these potentially beneficial substrates. Data
from animal studies and small observational studies in humans suggest that DPP-4
inhibitors may potentially reduce CV risk. However, recently completed CV outcome
trials in patients with T2DM and CV disease or at high risk of adverse CV events
have shown that the DPP-4 inhibitors saxagliptin and alogliptin neither increased
nor decreased major adverse CV events.
PMID- 25852134
TI - Effect of heating rate on highly heat-resistant spore-forming microorganisms.
AB - Highly heat-resistant spore-forming Bacillus cause nonsterility problems in
canned food and reduce the shelf life of many processed foods. The aim of this
research was to evaluate the thermal inactivation of Bacillus sporothermodurans
IIC65, Bacillus subtilis IC9, and Geobacillus stearothermophilus T26 under
isothermal and nonisothermal conditions. The data obtained showed that B.
sporothermodurans and B. subtilis were more heat resistant than G.
stearothermophilus. The survival curves of B. sporothermodurans and B. subtilis
showed shoulders, while the survival curves of G. stearothermophilus showed
tails. Under nonisothermal treatment, at heating rates of 1 and 20 C/min, time
needed to completely inactivate G. stearothermophilus was shorter than that
required for B. sporothermodurans and B. subtilis. In complex heat treatments
(heating-holding-cooling), the survival curves of B. sporothermodurans and B.
subtilis showed the same activation shoulders than those obtained under
isothermal treatments and the activation shoulders were again absent in the case
of G. stearothermophilus. Predictions fitted quite well the data obtained for B.
sporothermodurans. In contrast, the data for B. subtilis showed half a log cycle
more survival than expected and in the case of G. stearothermophilus, the
survival curve obtained showed much higher inactivation than expected.
PMID- 25852135
TI - l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of
nuclear factor kappaB and down-regulation of transforming growth factor beta and
connective tissue growth factor.
AB - Here we evaluated the ability of L-theanine in preventing experimental hepatic
cirrhosis and investigated the roles of nuclear factor-kappaB (NF-kappaB)
activation as well as transforming growth factor beta (TGF-beta) and connective
tissue growth factor (CTGF) regulation. Experimental hepatic cirrhosis was
established by the administration of carbon tetrachloride (CCl4) to rats (0.4
g/kg, intraperitoneally, three times per week, for 8 weeks), and at the same
time, adding L-theanine (8.0 mg/kg) to the drinking water. Rats had ad libitum
access to water and food throughout the treatment period. CCl4 treatment promoted
NF-kappaB activation and increased the expression of both TGF-beta and CTGF. CCl4
increased the serum activities of alanine aminotransferase and gamma-glutamyl
transpeptidase and the degree of lipid peroxidation, and it also induced a
decrease in the glutathione and glutathione disulfide ratio. L-Theanine prevented
increased expression of NF-kappaB and down-regulated the pro-inflammatory
(interleukin (IL)-1beta and IL-6) and profibrotic (TGF-beta and CTGF) cytokines.
Furthermore, the levels of messenger RNA encoding these proteins decreased in
agreement with the expression levels. L-Theanine promoted the expression of the
anti-inflammatory cytokine IL-10 and the fibrolytic enzyme metalloproteinase-13.
Liver hydroxyproline contents and histopathological analysis demonstrated the
anti-fibrotic effect of l-theanine. In conclusion, L-theanine prevents CCl4
induced experimental hepatic cirrhosis in rats by blocking the main pro
inflammatory and pro-fibrogenic signals.
PMID- 25852136
TI - Metabolic changes in the urine of andrographolide sodium bisulfite-treated rats.
AB - In recent years, andrographolide sodium bisulfite (ASB) has been reported to
cause acute renal failure frequently in clinical practice. We hypothesized that
changes in metabolic profile could have occurred after administration of ASB. To
investigate the metabolic changes caused by ASB-induced nephrotoxicity,
metabonomics method was utilized to depict the urine metabolic characteristics
and find the specific urine biomarkers associated with ASB-induced
nephrotoxicity. Sprague-Dawley rats were randomly assigned into three
experimental groups. They received a single daily injection of vehicle (0.9%
sodium chloride solution) or ASB at a dose of 100 or 600 mg kg(-1) day(-1) for 7
days. Twelve-hour urine was collected after the last administration. The routine
urinalysis was measured by a urine automatic analyzer while urinary metabolites
were evaluated using gas chromatography/mass spectrometry. The acquired data were
processed by multivariate principal component analysis (PCA), partial least
squares discriminant analysis (PLS-DA), and orthogonal PLS-DA. After 7-day
administration of ASB, the positive urine samples in protein, occult blood, and
ketones were increased, presenting dose dependence. The PCA and PLS-DA models
were capable of distinguishing the difference between ASB-treated group and
control. Biomarkers such as 1,5-anhydroglucitol, d-erythro-sphingosine, and 2
ketoadipate were identified as the most influential factors in ASB-induced
nephrotoxicity.
PMID- 25852137
TI - Science and culture: Using fiction to make the case for basic research.
PMID- 25852139
TI - Potential and challenges of patient-generated health data for high-quality cancer
care.
PMID- 25852140
TI - Patient Centeredness and Engagement in Quality-of-Care Oncology Research.
AB - More than a decade after the Institute of Medicine (IOM) first studied the
quality of cancer care, obstacles to achieving high-quality care remain, and
studies suggest that cancer care is often not as patient centered, accessible,
coordinated, or evidence based as it could be. Patients, their families, and
clinicians face a wide range of complex and often confusing choices regarding
their health and health care concerns and require trustworthy information to
decide which options are best for them. The Patient-Centered Outcomes Research
Institute (PCORI) strives to fund clinical comparative effectiveness research,
guided by patients, caregivers, and the broader health care community, that will
provide high-integrity, evidence-based information to help people make informed
health care decisions. This mission is well aligned with the IOM's recent
conceptual framework and corresponding recommendations that recognize that
addressing the needs of patients with cancer and their families is the most
important component of a high-quality cancer care delivery system. PCORI seeks
the opportunity to partner with diverse interdisciplinary research teams who
demonstrate a strong commitment to the inclusion and engagement of patients and
stakeholders as they work to develop high-quality cancer care delivery systems.
We see rich opportunities for such partnership in the cancer care community,
given the wealth of well-established patient advocacy groups and organizations
and cutting-edge research institutions, all of which are working toward the
common goal of improving the quality of cancer care for patients and their
families. This article and the project it describes provide an example of an
avenue for advancing this goal.
PMID- 25852141
TI - Implementing a user-driven online quality improvement toolkit for cancer care.
AB - PURPOSE: Peer-to-peer collaboration within integrated health systems requires a
mechanism for sharing quality improvement lessons. The Veterans Health
Administration (VA) developed online compendia of tools linked to specific cancer
quality indicators. We evaluated awareness and use of the toolkits, variation
across facilities, impact of social marketing, and factors influencing toolkit
use. METHODS: A diffusion of innovations conceptual framework guided the
collection of user activity data from the Toolkit Series SharePoint site and an
online survey of potential Lung Cancer Care Toolkit users. RESULTS: The VA
Toolkit Series site had 5,088 unique visitors in its first 22 months; 5% of users
accounted for 40% of page views. Social marketing communications were correlated
with site usage. Of survey respondents (n = 355), 54% had visited the site, of
whom 24% downloaded at least one tool. Respondents' awareness of the lung cancer
quality performance of their facility, and facility participation in quality
improvement collaboratives, were positively associated with Toolkit Series site
use. Facility-level lung cancer tool implementation varied widely across tool
types. CONCLUSION: The VA Toolkit Series achieved widespread use and a high
degree of user engagement, although use varied widely across facilities. The most
active users were aware of and active in cancer care quality improvement. Toolkit
use seemed to be reinforced by other quality improvement activities. A
combination of user-driven tool creation and centralized toolkit development
seemed to be effective for leveraging health information technology to spread
disease-specific quality improvement tools within an integrated health care
system.
PMID- 25852142
TI - Supporting models to transition breast cancer survivors to primary care:
formative evaluation of a cancer care Ontario initiative.
AB - PURPOSE: Many breast cancer (BC) survivors continue to be seen by specialists for
routine follow-up care despite growing evidence that transitioning appropriate BC
survivors to primary care is safe and effective. We describe the formative
evaluation of an initiative involving the development and implementation of
sustainable models of follow-up care for BC survivors across 14 Regional Cancer
Centers (RCC) in Ontario, Canada. METHODS: After extensive consultation, each RCC
received catalyst funding for the initiative. Detailed work plans were developed
locally and submitted to Cancer Care Ontario. Each region had a designated lead
and support from primary care. Funding could be used to develop any aspect of the
model. Formative evaluation of each model was conducted with descriptive analysis
of the model created, including summative description of how resources were used,
the number of survivors transitioned, and preliminary results from patient
surveys of experience at transition. RESULTS: Each region developed a unique
model that included clearly identified structures and processes of care. All
regions used survivorship care plans and patient education materials. Three main
models of follow-up care were developed: (1) direct to primary care, (2)
transition clinic, and (3) shared care. A total of 3,418 BC survivors
transitioned between March 2012 and September 2013. Patient experience surveys
were distributed by 12 regions, gathering responses from 752 BC survivors, with
85% reporting that they felt adequately prepared for the transition. CONCLUSION:
Using the approach described, wide-scale transition of appropriate BC survivors
from oncology-led practice is feasible over a fairly short timeframe.
PMID- 25852143
TI - Variation in positron emission tomography use after colon cancer resection.
AB - PURPOSE: Colon cancer surveillance guidelines do not routinely include positron
emission tomography (PET) imaging; however, its use after surgical resection has
been increasing. We evaluated the secular patterns of PET use after surgical
resection of colon cancer among elderly patients and identified factors
associated with its increasing use. PATIENTS AND METHODS: We used the SEER-linked
Medicare database (July 2001 through December 2009) to establish a retrospective
cohort of patients age >= 66 years who had undergone surgical resection for colon
cancer. Postoperative PET use was assessed with the test for trends. Patient,
tumor, and treatment characteristics were analyzed using univariable and
multivariable logistic regression analyses. RESULTS: Of the 39,221 patients with
colon cancer, 6,326 (16.1%) had undergone a PET scan within 2 years after
surgery. The use rate steadily increased over time. The majority of PET scans had
been performed within 2 months after surgery. Among patients who had undergone a
PET scan, 3,644 (57.6%) had also undergone preoperative imaging, and 1,977
(54.3%) of these patients had undergone reimaging with PET within 2 months after
surgery. Marriage, year of diagnosis, tumor stage, preoperative imaging,
postoperative visit to a medical oncologist, and adjuvant chemotherapy were
significantly associated with increased PET use. CONCLUSION: PET use after colon
cancer resection is steadily increasing, and further study is needed to
understand the clinical value and effectiveness of PET scans and the reasons for
this departure from guideline-concordant care.
PMID- 25852144
TI - Random sampling of skewed distributions implies Taylor's power law of fluctuation
scaling.
AB - Taylor's law (TL), a widely verified quantitative pattern in ecology and other
sciences, describes the variance in a species' population density (or other
nonnegative quantity) as a power-law function of the mean density (or other
nonnegative quantity): Approximately, variance = a(mean)(b), a > 0. Multiple
mechanisms have been proposed to explain and interpret TL. Here, we show
analytically that observations randomly sampled in blocks from any skewed
frequency distribution with four finite moments give rise to TL. We do not claim
this is the only way TL arises. We give approximate formulae for the TL
parameters and their uncertainty. In computer simulations and an empirical
example using basal area densities of red oak trees from Black Rock Forest, our
formulae agree with the estimates obtained by least-squares regression. Our
results show that the correlated sampling variation of the mean and variance of
skewed distributions is statistically sufficient to explain TL under random
sampling, without the intervention of any biological or behavioral mechanisms.
This finding connects TL with the underlying distribution of population density
(or other nonnegative quantity) and provides a baseline against which more
complex mechanisms of TL can be compared.
PMID- 25852145
TI - Extended synaptotagmins (E-Syts): Architecture and dynamics of membrane contact
sites revealed.
PMID- 25852146
TI - A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for
RIP3 activation during necroptosis.
AB - Receptor-interacting protein kinase 3, RIP3, and a pseudokinase mixed lineage
kinase-domain like protein, MLKL, constitute the core components of the
necroptosis pathway, which causes programmed necrotic death in mammalian cells.
Latent RIP3 in the cytosol is activated by several upstream signals including the
related kinase RIP1, which transduces signals from the tumor necrosis factor
(TNF) family of cytokines. We report here that RIP3 activation following the
induction of necroptosis requires the activity of an HSP90 and CDC37 cochaperone
complex. This complex physically associates with RIP3. Chemical inhibitors of
HSP90 efficiently block necroptosis by preventing RIP3 activation. Cells with
knocked down CDC37 were unable to respond to necroptosis stimuli. Moreover, an
HSP90 inhibitor that is currently under clinical development as a cancer therapy
was able to prevent systemic inflammatory response syndrome in rats treated with
TNF-alpha. HSP90 and CDC37 cochaperone complex-mediated protein folding is thus
an important part of the RIP3 activation process during necroptosis.
PMID- 25852147
TI - High-spin Mn-oxo complexes and their relevance to the oxygen-evolving complex
within photosystem II.
AB - The structural and electronic properties of a series of manganese complexes with
terminal oxido ligands are described. The complexes span three different
oxidation states at the manganese center (III-V), have similar molecular
structures, and contain intramolecular hydrogen-bonding networks surrounding the
Mn-oxo unit. Structural studies using X-ray absorption methods indicated that
each complex is mononuclear and that oxidation occurs at the manganese centers,
which is also supported by electron paramagnetic resonance (EPR) studies. This
gives a high-spin Mn(V)-oxo complex and not a Mn(IV)-oxy radical as the most
oxidized species. In addition, the EPR findings demonstrated that the Fermi
contact term could experimentally substantiate the oxidation states at the
manganese centers and the covalency in the metal-ligand bonding. Oxygen-17
labeled samples were used to determine spin density within the Mn-oxo unit, with
the greatest delocalization occurring within the Mn(V)-oxo species (0.45 spins on
the oxido ligand). The experimental results coupled with density functional
theory studies show a large amount of covalency within the Mn-oxo bonds. Finally,
these results are examined within the context of possible mechanisms associated
with photosynthetic water oxidation; specifically, the possible identity of the
proposed high valent Mn-oxo species that is postulated to form during turnover is
discussed.
PMID- 25852148
TI - Robust and sustained immune activation in human Ebola virus infection.
PMID- 25852149
TI - Enzymatic functionalization of a nanobody using protein insertion technology.
AB - Antibody-based products constitute one of the most attractive biological
molecules for diagnostic, medical imagery and therapeutic purposes with very few
side effects. Their development has become a major priority of biotech and
pharmaceutical industries. Recently, a growing number of modified antibody-based
products have emerged including fragments, multi-specific and conjugate
antibodies. In this study, using protein engineering, we have functionalized the
anti-hen egg-white lysozyme (HEWL) camelid VHH antibody fragment (cAb-Lys3), by
insertion into a solvent-exposed loop of the Bacillus licheniformis beta
lactamase BlaP. We showed that the generated hybrid protein conserved its
enzymatic activity while the displayed nanobody retains its ability to inhibit
HEWL with a nanomolar affinity range. Then, we successfully implemented the
functionalized cAb-Lys3 in enzyme-linked immunosorbent assay, potentiometric
biosensor and drug screening assays. The hybrid protein was also expressed on the
surface of phage particles and, in this context, was able to interact
specifically with HEWL while the beta-lactamase activity was used to monitor
phage interactions. Finally, using thrombin-cleavage sites surrounding the
permissive insertion site in the beta-lactamase, we reported an expression system
in which the nanobody can be easily separated from its carrier protein.
Altogether, our study shows that insertion into the BlaP beta-lactamase
constitutes a suitable technology to functionalize nanobodies and allows the
creation of versatile tools that can be used in innovative biotechnological
assays.
PMID- 25852150
TI - Radioprotective effects of Sipunculus nudus L. polysaccharide combined with WR
2721, rhIL-11 and rhG-CSF on radiation-injured mice.
AB - This study investigated the radioprotective effect of Sipunculus nudus L.
polysaccharide (SNP) in combination with WR-2721, rhIL-11 and rhG-CSF on
irradiated mice. A total of 70 Imprinting Control Region (ICR) mice were divided
into seven groups: the control group, the model group and five administration
groups. All groups, except the control group, were exposed to a 5 Gy (60)Co gamma
ray beam. Blood parameters [including white blood cell (WBC), red blood cell
(RBC) and platelet counts and hemoglobin level] were assessed three days before
irradiation, and the on the 3rd, 7th and 14th days after irradiation. Spleen,
thymus and testicular indices, DNA contents of bone marrow cells, bone marrow
nucleated cells, sperm counts, superoxide dismutase (SOD), malondialdehyde (MDA),
testosterone and estradiol levels in the serum were assessed on the 14th day
after irradiation. The combined administration of SNP, WR-2721, rhIL-11 and rhG
CSF exerted synergistic recovery effects on peripheral blood WBC, RBC and
platelet counts and hemoglobin levels in irradiated mice, and synergistic
promotion effects on spleen, thymus, testicle, bone marrow nucleated cells and
sperm counts in irradiated mice. The synergistic administration increased the
serum SOD activities and serum testosterone content of irradiated mice, but
synergy decreased the content of serum MDA and estradiol in irradiated mice.
These results suggest that the combined administration of SNP, WR-2721, rhIL-11
and rhG-CSF should increase the efficacy of these drugs for acute radiation
sickness, protect immunity, hematopoiesis and the reproductive organs of
irradiated-damaged mice, and improve oxidation resistance in the body.
PMID- 25852152
TI - Aortic root ring sign: multimodality imaging of aortic root abscess.
PMID- 25852151
TI - Caudal epidural anesthesia during intracavitary brachytherapy for cervical
cancer.
AB - It has been suggested that pain control during intracavitary brachytherapy for
cervical cancer is insufficient in most hospitals in Japan. Our hospital began
using caudal epidural anesthesia during high-dose-rate (HDR) intracavitary
brachytherapy in 2011. The purpose of the present study was to retrospectively
investigate the effects of caudal epidural anesthesia during HDR intracavitary
brachytherapy for cervical cancer patients. Caudal epidural anesthesia for 34
cervical cancer patients was performed during HDR intracavitary brachytherapy
between October 2011 and August 2013. We used the patients' self-reported Numeric
Rating Scale (NRS) score at the first session of HDR intracavitary brachytherapy
as a subjective evaluation of pain. We compared NRS scores of the patients with
anesthesia with those of 30 patients who underwent HDR intracavitary
brachytherapy without sacral epidural anesthesia at our hospital between May 2010
and August 2011. Caudal epidural anesthesia succeeded in 33 patients (97%), and
the NRS score was recorded in 30 patients. The mean NRS score of the anesthesia
group was 5.17 +/- 2.97, significantly lower than that of the control group's
6.80 +/- 2.59 (P = 0.035). The caudal epidural block resulted in no side-effects.
Caudal epidural anesthesia is an effective and safe anesthesia option during HDR
intracavitary brachytherapy for cervical cancer.
PMID- 25852153
TI - Lung metastasis and pheochromocytomas: Detection using FDG PET/CT.
PMID- 25852154
TI - Long-term use of tamoxifen reduces the risk of dementia: a nationwide population
based cohort study.
AB - BACKGROUND: To assess the possible association between tamoxifen treatment and
the subsequent risk of dementia in patients with breast cancer, a population
based cohort study was conducted using the Taiwanese National Health Insurance
Research Database. METHODS: The study cohort contained 24 197 patients diagnosed
with breast cancer between 1 January 2000 and 31 December 2004. Among them, 16
556 cases received tamoxifen treatment and 7641 did not. Four women without
breast cancer were frequency matched to each case by age and index-year as the
cancer-free group. The outcome of the analysis of is dementia. Hazard ratios
(HRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox
proportional hazards regression models. RESULTS: Patients with breast cancer
exhibited a similar risk of developing dementia (adjusted HR = 0.95, 95% CI =
0.86-1.04) compared with the cancer-free group. In addition, among women
diagnosed with breast cancer, tamoxifen users exhibited a significant 17% lower
risk of dementia compared with those not using tamoxifen (adjusted HR = 0.83, 95%
CI = 0.69-0.98), but the significant difference was limited to 5 years or more
use (adjusted HR = 0.47, 95% CI = 0.32-0.69). Both tamoxifen and aromatase
inhibitor use had a joint effect, with a significantly lower risk of dementia
among patients. CONCLUSION: The results of this population-based cohort study
suggest that long-term use of tamoxifen in patients with breast cancer is
associated with a lower risk of dementia.
PMID- 25852155
TI - MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and
spermiogenesis.
AB - Spermatogenesis is composed of three distinctive phases, which include self
renewal of spermatogonia via mitosis, spermatocytes undergoing meiosis I/II and
post-meiotic development of haploid spermatids via spermiogenesis.
Spermatogenesis also involves condensation of chromatin in the spermatid head
before transformation of spermatids to spermatozoa. Epigenetic regulation refers
to changes of heritably cellular and physiological traits not caused by
modifications in the DNA sequences of the chromatin such as mutations. Major
advances have been made in the epigenetic regulation of spermatogenesis. In this
review, we address the roles and mechanisms of epigenetic regulators, with a
focus on the role of microRNAs and DNA methylation during mitosis, meiosis and
spermiogenesis. We also highlight issues that deserve attention for further
investigation on the epigenetic regulation of spermatogenesis. More importantly,
a thorough understanding of the epigenetic regulation in spermatogenesis will
provide insightful information into the etiology of some unexplained infertility,
offering new approaches for the treatment of male infertility.
PMID- 25852156
TI - Cell lineage allocation in equine blastocysts produced in vitro under varying
glucose concentrations.
AB - Equine embryos develop in vitro in the presence of high glucose concentrations,
but little is known about their requirements for development. We evaluated the
effect of glucose concentrations in medium on blastocyst development after ICSI.
In experiment 1, there were no significant differences in rates of blastocyst
formation among embryos cultured in our standard medium (DMEM/F-12), which
contained >16 mM glucose, and those cultured in a minimal-glucose embryo culture
medium (<1 mM; Global medium, GB), with either 0 added glucose for the first 5
days, then 20 mM (0-20) or 20 mM for the entire culture period (20-20). In
experiment 2, there were no significant differences in the rates of blastocyst
development (31-46%) for embryos cultured in four glucose treatments in GB (0-10,
0-20, 5-10, or 5-20). Blastocysts were evaluated by immunofluorescence for
lineage-specific markers. All cells stained positively for POU5F1. An inner
cluster of cells was identified that included presumptive primitive endoderm
cells (GATA6-positive) and presumptive epiblast (EPI) cells. The 5-20 treatment
resulted in a significantly lower number of presumptive EPI-lineage cells than
the 0-20 treatment did. GATA6-positive cells appeared to be allocated to the
primitive endoderm independent of the formation of an inner cell mass, as was
previously hypothesized for equine embryos. These data demonstrate that equine
blastocyst development is not dependent on high glucose concentrations during
early culture; rather, environmental glucose may affect cell allocation. They
also present the first analysis of cell lineage allocation in in vitro-fertilized
equine blastocysts. These findings expand our understanding of the factors that
affect embryo development in the horse.
PMID- 25852157
TI - Glycolytic dependency of high-level nitric oxide resistance and virulence in
Staphylococcus aureus.
AB - Staphylococcus aureus is a prolific human pathogen capable of causing severe
invasive disease with a myriad of presentations. The ability of S. aureus to
cause infection is strongly linked with its capacity to overcome the effects of
innate immunity, whether by directly killing immune cells or expressing factors
that diminish the impact of immune effectors. One such scenario is the induction
of lactic acid fermentation by S. aureus in response to host nitric oxide (NO.).
This fermentative activity allows S. aureus to balance redox during NO.-induced
respiration inhibition. However, little is known about the metabolic substrates
and pathways that support this activity. Here, we identify glycolytic hexose
catabolism as being essential for S. aureus growth in the presence of high levels
of NO.. We determine that glycolysis supports S. aureus NO. resistance by
allowing for ATP and precursor metabolite production in a redox-balanced and
respiration-independent manner. We further demonstrate that glycolysis is
required for NO. resistance during phagocytosis and that increased levels of
extracellular glucose limit the effectiveness of phagocytic killing by enhancing
NO. resistance. Finally, we demonstrate that S. aureus glycolysis is essential
for virulence in both sepsis and skin/soft tissue models of infection in a time
frame consistent with the induction of innate immunity and host NO. production.
IMPORTANCE: Staphylococcus aureus is a leading human bacterial pathogen capable
of causing a wide variety of diseases that, as a result of antibiotic resistance,
are very difficult to treat. The frequency of S. aureus tissue invasion suggests
that this bacterium has evolved to resist innate immunity and grow using the
nutrients present in otherwise sterile host tissue. We have identified glycolysis
as an essential component of S. aureus virulence and attribute its importance to
promoting nitric oxide resistance and growth under low oxygen conditions. Our
data suggest that diabetics, a patient population characterized by excess serum
glucose, may be more susceptible to S. aureus as a result of increased glucose
availability. Furthermore, the essential nature of S. aureus glycolysis indicates
that a newly developed glycolysis inhibitor may be a highly effective treatment
for S. aureus infections.
PMID- 25852158
TI - Coupled positive and negative feedbacks produce diverse gene expression patterns
in colonies.
AB - Formation of patterns is a common feature in the development of multicellular
organism as well as of microbial communities. To investigate the formation of
gene expression patterns in colonies, we build a mathematical model of two
dimensional colony growth, where cells carry a coupled positive-and-negative
feedback circuit. We demonstrate that the model can produce sectored, target
(concentric), uniform, and scattered expression patterns of regulators, depending
on gene expression dynamics and nutrient diffusion. We reconstructed the same
regulatory structure in Escherichia coli cells and found gene expression patterns
on the surface of colonies similar to the ones produced by the computer
simulations. By comparing computer simulations and experimental results, we
observed that very simple rules of gene expression can yield a spectrum of well
defined patterns in a growing colony. Our results suggest that variations of the
protein content among cells lead to a high level of heterogeneity in colonies.
IMPORTANCE: Formation of patterns is a common feature in the development of
microbial communities. In this work, we show that a simple genetic circuit
composed of a positive-feedback loop and a negative-feedback loop can produce
diverse expression patterns in colonies. We obtained similar sets of gene
expression patterns in the simulations and in the experiments. Because the
combination of positive feedback and negative feedback is common in intracellular
molecular networks, our results suggest that the protein content of cells is
highly diversified in colonies.
PMID- 25852159
TI - Genetic basis of persister tolerance to aminoglycosides in Escherichia coli.
AB - Persisters are dormant variants that form a subpopulation of drug-tolerant cells
largely responsible for the recalcitrance of chronic infections. However, our
understanding of the genetic basis of antibiotic tolerance remains incomplete. In
this study, we applied transposon sequencing (Tn-Seq) to systematically
investigate the mechanism of aminoglycoside tolerance in Escherichia coli. We
constructed a highly saturated transposon library that covered the majority of E.
coli genes and promoter regions and exposed a stationary-phase culture to a
lethal dose of gentamicin. Tn-Seq was performed to evaluate the survival of each
mutant to gentamicin exposure. We found that the disruption of several distinct
pathways affected gentamicin tolerance. We identified 105 disrupted gene/promoter
regions with a more than 5-fold reduction in gentamicin tolerance and 37 genes
with a more than 5-fold increased tolerance. Functional cluster analysis suggests
that deficiency in motility and amino acid synthesis significantly diminished
persisters tolerant to gentamicin, without changing the MIC. Amino acid
auxotrophs, including serine, threonine, glutamine, and tryptophan auxotrophs,
exhibit strongly decreased tolerance to gentamicin, which cannot be restored by
supplying the corresponding amino acids to the culture. Interestingly, supplying
these amino acids to wild-type E. coli sensitizes stationary-phase cells to
gentamicin, possibly through the inhibition of amino acid synthesis. In addition,
we found that the deletion of amino acid synthesis genes significantly increases
gentamicin uptake in stationary phase, while the deletion of flagellar genes does
not affect gentamicin uptake. We conclude that activation of motility and amino
acid biosynthesis contributes to the formation of persisters tolerant to
gentamicin. IMPORTANCE: Persisters are responsible for the recalcitrance of
chronic infections to antibiotics. The pathways of persister formation in E. coli
are redundant, and our understanding of the mechanism of persister formation is
incomplete. Using a highly saturated transposon insertion library, we
systematically analyzed the contribution of different cellular processes to the
formation of persisters tolerant to aminoglycosides. Unexpectedly, we found that
activation of amino acid synthesis and motility strongly contributes to persister
formation. The approach used in this study leads to an understanding of
aminoglycoside tolerance and provides a general method to identify genes
affecting persister formation.
PMID- 25852160
TI - Characterization of H5N1 influenza virus variants with hemagglutinin mutations
isolated from patients.
AB - A change in viral hemagglutinin (HA) receptor binding specificity from alpha2,3-
to alpha2,6-linked sialic acid is necessary for highly pathogenic avian influenza
(AI) virus subtype H5N1 to become pandemic. However, details of the human
adaptive change in the H5N1 virus remain unknown. Our database search of H5N1
clade 2.2.1 viruses circulating in Egypt identified multiple HA mutations that
had been selected in infected patients. Using reverse genetics, we found that
increases in both human receptor specificity and the HA pH threshold for membrane
fusion were necessary to facilitate replication of the virus variants in human
airway epithelia. Furthermore, variants with enhanced replication in human cells
had decreased HA stability, apparently to compensate for the changes in viral
receptor specificity and membrane fusion activity. Our findings showed that H5N1
viruses could rapidly adapt to growth in the human airway microenvironment by
altering their HA properties in infected patients and provided new insights into
the human-adaptive mechanisms of AI viruses. IMPORTANCE: Circulation between bird
and human hosts may allow H5N1 viruses to acquire amino acid changes that
increase fitness for human infections. However, human-adaptive changes in H5N1
viruses have not been adequately investigated. In this study, we found that
multiple HA mutations were actually selected in H5N1-infected patients and that
H5N1 variants with some of these HA mutations had increased human-type receptor
specificity and increased HA membrane fusion activity, both of which are
advantageous for viral replication in human airway epithelia. Furthermore, HA
mutants selected during viral replication in patients were likely to have less HA
stability, apparently as a compensatory mechanism. These results begin to clarify
the picture of the H5N1 human-adaptive mechanism.
PMID- 25852162
TI - Reply to '"Mycobacterium indicus pranii" is a strain of Mycobacterium
intracellulare': "M. indicus pranii" is a distinct strain, not derived from M.
intracellulare, and is an organism at an evolutionary transition point between a
fast grower and slow grower.
PMID- 25852161
TI - Over 150 years of long-term fertilization alters spatial scaling of microbial
biodiversity.
AB - Spatial scaling is a critical issue in ecology, but how anthropogenic activities
like fertilization affect spatial scaling is poorly understood, especially for
microbial communities. Here, we determined the effects of long-term fertilization
on the spatial scaling of microbial functional diversity and its relationships to
plant diversity in the 150-year-old Park Grass Experiment, the oldest continuous
grassland experiment in the world. Nested samples were taken from plots with
contrasting inorganic fertilization regimes, and community DNAs were analyzed
using the GeoChip-based functional gene array. The slopes of microbial gene-area
relationships (GARs) and plant species-area relationships (SARs) were estimated
in a plot receiving nitrogen (N), phosphorus (P), and potassium (K) and a control
plot without fertilization. Our results indicated that long-term inorganic
fertilization significantly increased both microbial GARs and plant SARs.
Microbial spatial turnover rates (i.e., z values) were less than 0.1 and were
significantly higher in the fertilized plot (0.0583) than in the control plot
(0.0449) (P < 0.0001). The z values also varied significantly with different
functional genes involved in carbon (C), N, P, and sulfur (S) cycling and with
various phylogenetic groups (archaea, bacteria, and fungi). Similarly, the plant
SARs increased significantly (P < 0.0001), from 0.225 in the control plot to
0.419 in the fertilized plot. Soil fertilization, plant diversity, and spatial
distance had roughly equal contributions in shaping the microbial functional
community structure, while soil geochemical variables contributed less. These
results indicated that long-term agricultural practice could alter the spatial
scaling of microbial biodiversity. IMPORTANCE: Determining the spatial scaling of
microbial biodiversity and its response to human activities is important but
challenging in microbial ecology. Most studies to date are based on different
sites that may not be truly comparable or on short-term perturbations, and hence,
the results observed could represent transient responses. This study examined the
spatial patterns of microbial communities in response to different fertilization
regimes at the Rothamsted Research Experimental Station, which has become an
invaluable resource for ecologists, environmentalists, and soil scientists. The
current study is the first showing that long-term fertilization has dramatic
impacts on the spatial scaling of microbial communities. By identifying the
spatial patterns in response to long-term fertilization and their underlying
mechanisms, this study makes fundamental contributions to predictive
understanding of microbial biogeography.
PMID- 25852163
TI - Intrahost dynamics of antiviral resistance in influenza A virus reflect complex
patterns of segment linkage, reassortment, and natural selection.
AB - Resistance following antiviral therapy is commonly observed in human influenza
viruses. Although this evolutionary process is initiated within individual hosts,
little is known about the pattern, dynamics, and drivers of antiviral resistance
at this scale, including the role played by reassortment. In addition, the short
duration of human influenza virus infections limits the available time window in
which to examine intrahost evolution. Using single-molecule sequencing, we
mapped, in detail, the mutational spectrum of an H3N2 influenza A virus
population sampled from an immunocompromised patient who shed virus over a 21
month period. In this unique natural experiment, we were able to document the
complex dynamics underlying the evolution of antiviral resistance. Individual
resistance mutations appeared weeks before they became dominant, evolved
independently on cocirculating lineages, led to a genome-wide reduction in
genetic diversity through a selective sweep, and were placed into new
combinations by reassortment. Notably, despite frequent reassortment,
phylogenetic analysis also provided evidence for specific patterns of segment
linkage, with a strong association between the hemagglutinin (HA)- and matrix (M)
encoding segments that matches that previously observed at the epidemiological
scale. In sum, we were able to reveal, for the first time, the complex
interaction between multiple evolutionary processes as they occur within an
individual host. IMPORTANCE: Understanding the evolutionary forces that shape the
genetic diversity of influenza virus is crucial for predicting the emergence of
drug-resistant strains but remains challenging because multiple processes occur
concurrently. We characterized the evolution of antiviral resistance in a single
persistent influenza virus infection, representing the first case in which
reassortment and the complex patterns of drug resistance emergence and evolution
have been determined within an individual host. Deep-sequence data from multiple
time points revealed that the evolution of antiviral resistance reflects a
combination of frequent mutation, natural selection, and a complex pattern of
segment linkage and reassortment. In sum, these data show how immunocompromised
hosts may help reveal the drivers of strain emergence.
PMID- 25852164
TI - The transcription factor FoxK participates with Nup98 to regulate antiviral gene
expression.
AB - Upon infection, pathogen recognition leads to a rapidly activated gene expression
program that induces antimicrobial effectors to clear the invader. We recently
found that Nup98 regulates the expression of a subset of rapidly activated
antiviral genes to restrict disparate RNA virus infections in Drosophila by
promoting RNA polymerase occupancy at the promoters of these antiviral genes. How
Nup98 specifically targets these loci was unclear; however, it is known that
Nup98 participates with transcription factors to regulate developmental-gene
activation. We reasoned that additional transcription factors may facilitate the
Nup98-dependent expression of antiviral genes. In a genome-wide RNA interference
(RNAi) screen, we identified a relatively understudied forkhead transcription
factor, FoxK, as active against Sindbis virus (SINV) in Drosophila. Here we find
that FoxK is active against the panel of viruses that are restricted by Nup98,
including SINV and vesicular stomatitis virus (VSV). Mechanistically, we show
that FoxK coordinately regulates the Nup98-dependent expression of antiviral
genes. Depletion of FoxK significantly reduces Nup98-dependent induction of
antiviral genes and reduces the expression of a forkhead response element
containing luciferase reporter. Together, these data show that FoxK-mediated
activation of gene expression is Nup98 dependent. We extended our studies to
mammalian cells and found that the mammalian ortholog FOXK1 is antiviral against
two disparate RNA viruses, SINV and VSV, in human cells. Interestingly, FOXK1
also plays a role in the expression of antiviral genes in mammals: depletion of
FOXK1 attenuates virus-inducible interferon-stimulated response element (ISRE)
reporter expression. Overall, our results demonstrate a novel role for FOXK1 in
regulating the expression of antiviral genes, from insects to humans. IMPORTANCE:
Innate immunity is characterized by rapid gene expression programs, from insects
to mammals. Furthermore, we find that Nup98, known for its roles in the nuclear
pore, plays a noncanonical role in binding the promoters and poising a subset of
loci for rapid antiviral gene induction. It was unclear how Nup98 accesses these
specific genes, and we here demonstrate that Nup98 cooperates with the
transcription factor FoxK to regulate this gene expression program. Depletion of
FoxK specifically reduces the induction of Nup98-dependent genes. Further, we
find that the antiviral function of FoxK is conserved, as the human ortholog
FOXK1 is also antiviral and regulates gene expression from virus-induced
promoters. Although other forkhead transcription factors have been implicated in
immunity, a role for FoxK in antiviral defense was previously unappreciated. Our
findings reveal a conserved and novel role for FoxK in coordinating with Nup98 to
promote a robust and complex antiviral transcriptional response.
PMID- 25852165
TI - USA300 and USA500 clonal lineages of Staphylococcus aureus do not produce a
capsular polysaccharide due to conserved mutations in the cap5 locus.
AB - The surface capsular polysaccharide (CP) is a virulence factor that has been used
as an antigen in several successful vaccines against bacterial pathogens. A
vaccine has not yet been licensed against Staphylococcus aureus, although two
multicomponent vaccines that contain CP antigens are in clinical trials. In this
study, we evaluated CP production in USA300 methicillin-resistant S. aureus
(MRSA) isolates that have become the predominant community-associated MRSA clones
in the United States. We found that all 167 USA300 MRSA and 50 USA300 methicillin
susceptible S. aureus (MSSA) isolates were CP negative (CP(-)). Moreover, all 16
USA500 isolates, which have been postulated to be the progenitor lineage of
USA300, were also CP(-). Whole-genome sequence analysis of 146 CP(-) USA300 MRSA
isolates revealed they all carry a cap5 locus with 4 conserved mutations compared
with strain Newman. Genetic complementation experiments revealed that three of
these mutations (in the cap5 promoter, cap5D nucleotide 994, and cap5E nucleotide
223) ablated CP production in USA300 and that Cap5E75 Asp, located in the
coenzyme-binding domain, is essential for capsule production. All but three
USA300 MSSA isolates had the same four cap5 mutations found in USA300 MRSA
isolates. Most isolates with a USA500 pulsotype carried three of these four
USA300-specific mutations, suggesting the fourth mutation occurred in the USA300
lineage. Phylogenetic analysis of the cap loci of our USA300 isolates as well as
publicly available genomes from 41 other sequence types revealed that the USA300
specific cap5 mutations arose sequentially in S. aureus in a common ancestor of
USA300 and USA500 isolates. IMPORTANCE: The USA300 MRSA clone emerged as a
community-associated pathogen in the United States nearly 20 years ago. Since
then, it has rapidly disseminated and now causes health care-associated
infections. This study shows that the CP-negative (CP(-)) phenotype has persisted
among USA300 isolates and is a universal and characteristic trait of this highly
successful MRSA lineage. It is important to note that a vaccine consisting solely
of CP antigens would not likely demonstrate high efficacy in the U.S. population,
where about half of MRSA isolates comprise USA300. Moreover, conversion of a
USA300 strain to a CP-positive (CP(+)) phenotype is unlikely in vivo or in vitro
since it would require the reversion of 3 mutations. We have also established
that USA300 MSSA isolates and USA500 isolates are CP(-) and provide new insight
into the evolution of the USA300 and USA500 lineages.
PMID- 25852166
TI - Effect of Weight Loss on Postural Changes in Pulmonary Function in Obese
Subjects: A Longitudinal Study.
AB - BACKGROUND: Postural changes are known to affect normal lung volumes. A reduction
in sitting to supine functional residual capacity (FRC) is well-described in non
obese subjects adopting a supine position. However, postural changes in lung
volumes in the obese require further exploration. We aimed to longitudinally
address the effects of weight loss on postural changes in lung volumes and
pulmonary function in obese subjects. We tested the hypothesis that supine
reduction in FRC would be absent in morbid obesity and recovered upon weight
loss. METHODS: This was a prospective, observational, longitudinal study.
Consecutive morbidly obese adults (N = 12, age: 44 +/- 14 y, body mass index: 45
+/- 5 kg/m(2)) enrolled in a bariatric surgery program were included. Standard
pulmonary function tests and blood gas analysis were performed both before and 1
y after surgery. Pulmonary function was assessed in both the sitting and supine
position using spirometry and multi-breath helium dilution. Parameters recorded
before and after weight loss were compared. The main outcome measure was FRC.
RESULTS: Ten subjects were retested 1 y after surgery (body mass index: 31 +/- 5
kg/m(2)). FRC was not affected by change in posture before surgery. Supine
reduction in FRC was observed after weight loss (DeltaFRC: -0.6 +/- 0.4 L,
sitting vs supine, P = .002). Pulmonary gas exchange improved (alveolar-to
arterial oxygen partial pressure difference: -8 +/- 11 mm Hg, P = .035).
CONCLUSIONS: Although postural change in FRC is absent when the morbidly obese
adopt a supine position, supine reduction in FRC can be recovered following
gastroplasty-induced weight loss, despite residual mild to moderate obesity. This
also shows that mild to moderate obesity may affect supine FRC more than morbid
obesity. (ClinicalTrials.gov registration NCT02207192.).
PMID- 25852168
TI - Bronchoconstriction in response to deep inhalation during spirometry testing.
PMID- 25852167
TI - Use of Accelerometry to Monitor Physical Activity in Critically Ill Subjects: A
Systematic Review.
AB - Medical management of critically ill patients often incorporates prolonged bed
rest, which, in combination with the underlying illness, results in global muscle
weakness and atrophy. Recent evidence has demonstrated improvements in clinical
and functional outcomes when exercise and physical activity are incorporated
early in the management of ICU patients. Accurate monitoring of ICU patients'
physical activity is essential for proper prescription and escalation of activity
levels. Accelerometry is a technique used to measure physical activity and has
been validated in several ambulatory populations. However, its use in critically
ill, hospitalized patients with poor functional mobility is limited. In this
review, we focus on the few studies assessing the use of accelerometry to measure
physical activity in the care of mechanically ventilated adult ICU patients. The
selected literature demonstrates that accelerometry correlates well with direct
observation in reporting frequency and duration of various types of physical
activity (rolling, sitting up, transferring, walking), but cannot differentiate
various intensities of activity or whether movements are voluntary or involuntary
with respect to effort. Thus, although accelerometry may serve as a useful
adjunct in reporting temporality of physical activity in critically ill patients,
other objective information may be needed to accurately record frequency,
duration, and intensity of activity in this population.
PMID- 25852169
TI - Concordant dysregulation of miR-5p and miR-3p arms of the same precursor microRNA
may be a mechanism in inducing cell proliferation and tumorigenesis: a lung
cancer study.
AB - A precursor microRNA (miRNA) has two arms: miR-5p and miR-3p (miR-5p/-3p).
Depending on the tissue or cell types, both arms can become functional. However,
little is known about their coregulatory mechanisms during the tumorigenic
process. Here, by using the large-scale miRNA expression profiles of five cancer
types, we revealed that several of miR-5p/-3p arms were concordantly dysregulated
in each cancer. To explore possible coregulatory mechanisms of concordantly
dysregulated miR-5p/-3p pairs, we developed a robust computational framework and
applied it to lung cancer data. The framework deciphers miR-5p/-3p coregulated
protein interaction networks critical to lung cancer development. As a novel part
in the method, we uniquely applied the second-order partial correlation to
minimize false-positive regulations. Using 279 matched miRNA and mRNA expression
profiles extracted from tumor and normal lung tissue samples, we identified 17
aberrantly expressed miR-5p/-3p pairs that potentially modulate the gene
expression of 35 protein complexes. Functional analyses revealed that these
complexes are associated with cancer-related biological processes, suggesting the
oncogenic potential of the reported miR-5p/-3p pairs. Specifically, we revealed
that the reduced expression of miR-145-5p/-3p pair potentially contributes to
elevated expression of genes in the "FOXM1 transcription factor network" pathway,
which may consequently lead to uncontrolled cell proliferation. Subsequently, the
regulation of miR-145-5p/-3p in the FOXM1signaling pathway was validated by a
cohort of 104 matched miRNA and protein (reverse-phase protein array) expression
profiles in lung cancer. In summary, our computational framework provides a novel
tool to study miR-5p/-3p coregulatory mechanisms in cancer and other diseases.
PMID- 25852171
TI - Identification of stable reference genes in differentiating human pluripotent
stem cells.
AB - Reference genes, often referred to as housekeeping genes (HKGs), are frequently
used to normalize gene expression data based on the assumption that they are
expressed at a constant level in the cells. However, several studies have shown
that there may be a large variability in the gene expression levels of HKGs in
various cell types. In a previous study, employing human embryonic stem cells
(hESCs) subjected to spontaneous differentiation, we observed that the expression
of commonly used HKG varied to a degree that rendered them inappropriate to use
as reference genes under those experimental settings. Here we present a
substantially extended study of the HKG signature in human pluripotent stem cells
(hPSC), including nine global gene expression datasets from both hESC and human
induced pluripotent stem cells, obtained during directed differentiation toward
endoderm-, mesoderm-, and ectoderm derivatives. Sets of stably expressed genes
were compiled, and a handful of genes (e.g., EID2, ZNF324B, CAPN10, and RABEP2)
were identified as generally applicable reference genes in hPSCs across all cell
lines and experimental conditions. The stability in gene expression profiles was
confirmed by reverse transcription quantitative PCR analysis. Taken together, the
current results suggest that differentiating hPSCs have a distinct HKG signature,
which in some aspects is different from somatic cell types, and underscore the
necessity to validate the stability of reference genes under the actual
experimental setup used. In addition, the novel putative HKGs identified in this
study can preferentially be used for normalization of gene expression data
obtained from differentiating hPSCs.
PMID- 25852170
TI - Exoelectrogenic capacity of host microbiota predicts lymphocyte recruitment to
the gut.
AB - Electrotaxis, directional cell movement in response to an electric potential, has
been demonstrated in a wide range of cell types including lymphocytes.
Exoelectrogens, microorganisms capable of generating electrical currents, have
been identified in microbial fuel cells. However, no studies have investigated
exoelectrogenic microbes in fresh feces or the effects of an exoelectrogenic
microbiota on the host organism. Here we show that commensal gut microbial
populations differ in their capacity for electrical current production by
exoelectrogens and that those differences are predictive of increased lymphocyte
trafficking to the gut in vivo, despite the lack of increased production of
canonical lymphocyte-specific chemokines. Additionally, we demonstrate that the
difference in current production between mice purchased from different commercial
sources correlates reproducibly with the presence or absence of segmented
filamentous bacteria, and while our data do not support a direct role for
segmented filamentous bacteria in ex vivo current production, an exoelectrogenic
microbiota can be transferred in vivo via mucosa-associated bacteria present in
the ileum. Moreover, we detect upregulation of microbial genes associated with
extracellular electron transfer in feces of mice colonized with exoelectrogenic
microbiota containing segmented filamentous bacteria. While still correlative,
these results suggest a novel means by which the gut microbiota modulates the
recruitment of cells of the immune system to the gut.
PMID- 25852173
TI - Influenza vaccine efficacy.
PMID- 25852174
TI - Better treatment for depression.
PMID- 25852175
TI - Better treatment for depression.
PMID- 25852176
TI - Better treatment for depression.
PMID- 25852177
TI - Penicillin VK oral suspension.
PMID- 25852178
TI - Figure caption.
PMID- 25852179
TI - Forum.
PMID- 25852180
TI - Traumatization in Deaf and Hard-of-Hearing Adult Psychiatric Outpatients.
AB - Deaf and hard-of-hearing persons are at risk for experiencing traumatic events
and such experiences are associated with symptoms of mental disorder. We
investigated the prevalence of traumatic events and subsequent traumatization in
adults referred to specialized psychiatric outpatient units for deaf and hard-of
hearing patients. Sixty-two patients were diagnosed with mental disorders and
assessed for potential traumatic experiences in their preferred language and mode
of communication using instruments translated into Norwegian Sign Language. All
patients reported traumatic events, with a mean of 6.2 different types; 85%
reported subsequent traumatization not significantly associated with either
residential school setting or communicative competence of childhood caregivers.
Traumatization patterns in both sexes were similar to those in hearing clinical
samples. Findings indicate that psychiatric intake interviews should routinely
assess potentially traumatic events and their impacts, and that mental health
professionals working with deaf and hard-of-hearing patients should be able to
treat trauma-related disorders.
PMID- 25852181
TI - Radiation doses in chest, abdomen and pelvis CT procedures.
AB - Computed tomography (CT) scanning is recognised as a high-radiation dose modality
and estimated to be 17 % of the radiological procedure and responsible for 70 %
of medical radiation exposure. Although diagnostic X rays provide great benefits,
their use involves some risk for developing cancer. The objectives of this study
are to estimate radiation doses during chest, abdomen and pelvis CT. A total of
51 patients were examined for the evaluation of metastasis of a diagnosed primary
tumour during 4 months. A calibrated CT machine from Siemens 64 slice was used.
The mean age was 48.0 +/- 18.6 y. The mean patient weight was 73.8 +/- 16.1 kg.
The mean dose-length product was 1493.8 +/- 392.1 mGy cm, Volume CT dose index
(CTDI vol) was 22.94 +/- 5.64 mGy and the mean effective dose was 22.4 +/- 5.9
mSv per procedure. The radiation dose per procedure was higher as compared with
previous studies. Therefore, the optimisation of patient's radiation doses is
required in order to reduce the radiation risk.
PMID- 25852182
TI - Radiation dose levels for conventional chest and abdominal X-ray procedures in
elected hospitals in Sudan.
AB - This study aimed to assess patient entrance surface air kerma (ESAK) during chest
and abdominal X-ray procedures in screen film radiography (SFR) and computed
radiography (CR) to establish dose reference levels. Patients' doses were
measured in five hospitals for a total of 196 patients. ESAK was calculated from
exposure parameters using DosCal software. The X-ray tube output (mGy mAs(-1)),
accuracy of exposure factors, linearity and reproducibility were measured using
an Unfors Xi dosimeter. The overall mean and range of ESAK during chest X-ray
were 0.6 +/- 0.3 (0.1-1.3) mGy, while for abdominal X-rays they were 4.0 +/- 3.2
(1.3-9.2) mGy. Hospital with a CR system was found to use relatively higher
doses. Dose values for abdominal X-ray procedures were comparable with previous
studies. The dose for chest X-ray procedure was higher by a factor of 2-3
compared with the current international reference levels.
PMID- 25852183
TI - Examination of the relevance of using radiochromic films in measuring entrance
skin dose distribution in conventional digital mammography.
AB - Based on manufacturer specifications, radiochromic films are sensitive enough to
be used for dosimetry in digital mammography (DM). The aim of this work was to
study the feasibility of measuring entrance surface dose (ESD) distribution using
Gafchromic XR-QA2 films. The films were irradiated following a standard clinical
two-view screening mammography protocol using a full-field digital mammography
(FFDM) imaging system. The films were then digitised using a flatbed scanner. The
calibration curve relating the readings from a calibrated ionisation chamber and
the films' net optical density (NOD) could not be obtained. The examination of
the calibration data revealed non-sensitivity of the films to resolve dose
differences below 20 mGy at 28 kVp. Therefore, radiochromic films were found not
to be suitable for measuring ESD profiles in DM. A 2D map of the NOD of the
irradiated films obtained using in-house developed MATLAB computer program is
presented.
PMID- 25852184
TI - Focus issue: Tackling reproducibility and accuracy in cell signaling experiments.
AB - With contributions from the Board of Reviewing Editors and the Chief Scientific
Editor, Science Signaling highlights some common concerns surrounding
reproducibility and issues related to appropriate methodological considerations
for accurately quantifying and then modeling regulatory phenomena. Specific
topics include sources of error, understanding biological "n" and the application
of appropriate statistical analyses, quantitative Western blotting, quantitative
mass spectrometry-based proteomics, and parameterization for establishing
quantitative models of cellular networks.
PMID- 25852185
TI - Reproducibility in science.
AB - The issue of reproducibility and reliability in science has come to the forefront
in light of several high-profile studies that could not be reproduced. Whereas
some errors in reliability can be attributed to the application of new techniques
that have unappreciated caveats, some problems with reproducibility lie in the
climate of intense pressure for funding and to publish faced by many researchers.
PMID- 25852186
TI - Criteria for biological reproducibility: what does "n" mean?
AB - This Focus tackles the issue of technical versus biological replicates, what
constitutes appropriate biological replicates, and appropriate statistical
analysis for data with small sample sizes.
PMID- 25852187
TI - Good practices for building dynamical models in systems biology.
AB - Dynamic models can offer deep understanding of information processing mechanisms
in physiology, cell signaling, and biological regulation when they are
appropriately detailed. Here, we describe some of the key aspects of the model
building process, including proper parameterization and error analysis, as well
as common mistakes, such as model-tweaking and oversimplification, which can
decrease the value of the models.
PMID- 25852188
TI - Quantitative mass spectrometry of posttranslational modifications: keys to
confidence.
AB - Posttranslational modifications (PTMs) of proteins represent an important level
of cellular control. They participate in the efficient transduction of signals
and form the basis of long-term cellular memory, allowing cells to adapt to a
rapidly changing environment. More than 200 different PTMs have been described
that affect many aspects of protein functions, and the importance of these
modifications is evident from the number of diseases that arise from their
deregulation. The proteome-wide analysis of certain PTMs, such as
phosphorylation, acetylation, glycosylation, methylation, ubiquitination, and
sumoylation, has become a standard procedure in many laboratories. We highlight
and discuss some important aspects of systems-wide PTM analyses using mass
spectrometry-based methods.
PMID- 25852189
TI - An analysis of critical factors for quantitative immunoblotting.
AB - Immunoblotting (also known as Western blotting) combined with digital image
analysis can be a reliable method for analyzing the abundance of proteins and
protein modifications, but not every immunoblot-analysis combination produces an
accurate result. I illustrate how sample preparation, protocol implementation,
detection scheme, and normalization approach profoundly affect the quantitative
performance of immunoblotting. This study implemented diagnostic experiments that
assess an immunoblot-analysis workflow for accuracy and precision. The results
showed that ignoring such diagnostics can lead to pseudoquantitative immunoblot
data that markedly overestimate or underestimate true differences in protein
abundance.
PMID- 25852190
TI - Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a
source of potential targets for combination therapy.
AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous
secreted peptide and, in preclinical studies, preferentially induces apoptosis in
tumor cells rather than in normal cells. The acquisition of resistance in cells
exposed to TRAIL or its mimics limits their clinical efficacy. Because kinases
are intimately involved in the regulation of apoptosis, we systematically
characterized kinases involved in TRAIL signaling. Using RNA interference (RNAi)
loss-of-function and cDNA overexpression screens, we identified 169 protein
kinases that influenced the dynamics of TRAIL-induced apoptosis in the colon
adenocarcinoma cell line DLD-1. We classified the kinases as sensitizers or
resistors or modulators, depending on the effect that knockdown and
overexpression had on TRAIL-induced apoptosis. Two of these kinases that were
classified as resistors were PX domain-containing serine/threonine kinase (PXK)
and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may
enable cells to resist TRAIL-induced apoptosis by enhancing endocytosis of the
TRAIL receptors. We assembled protein interaction maps using mass spectrometry
based protein interaction analysis and quantitative phosphoproteomics. With these
protein interaction maps, we modeled information flow through the networks and
identified apoptosis-modifying kinases that are highly connected to regulated
substrates downstream of TRAIL. The results of this analysis provide a resource
of potential targets for the development of TRAIL combination therapies to
selectively kill cancer cells.
PMID- 25852192
TI - Limbic pathway lesions in patients with multiple sclerosis.
AB - BACKGROUND: Multiple sclerosis (MS) is a well-known demyelinating disease to
cause cognitive dysfunction. The limbic system, relevant to memory, can be easily
overlooked in conventional magnetic resonance imaging (MRI). PURPOSE: To
investigate the distribution and frequency of demyelinating lesions affecting
white matter connections of the limbic system based on localization with
diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) color maps
compared to three-dimensional T2-weighted (T2W) and FLAIR volumes in MS patients.
MATERIAL AND METHODS: One hundred and fifty patients with a known diagnosis of MS
were identified for this Health Insurance Portability and Accountability (HIPAA)
compliant retrospective cross-sectional study. DTI-derived FA color maps, co
registered to T2W and FLAIR images, were analyzed for lesions affecting the three
white matter tracts of the limbic system including cingulum, fornix, and
mammilothalamic tracts by two investigators. The approximate location of the
lesions on FLAIR was always confirmed on the co-registered DTI-derived FA color
maps. RESULTS: Of the 150 patients analyzed, 14.6% had cingulum lesions, 2.6% had
fornix lesions, and 2.6% had mammilothalamic tract lesions; 21.3% of patients had
at least one of the three tracts affected. CONCLUSION: A relatively high
frequency of lesions involving the limbic tracts may explain memory deficits and
emotional dysfunction commonly experienced by patients with MS. The combined
information from T2W, FLAIR, and DTI-derived FA color map allowed for more
accurate localization of lesions affecting the major white matter tracts of the
limbic system.
PMID- 25852194
TI - Estimating effective dose from 3D imaging with interventional fluoroscopy systems
using limited exposure data.
AB - BACKGROUND: Estimations of the effective dose from three-dimensional (3D)
rotational imaging with interventional fluoroscopy systems are hampered by the
fact that not all systems provide individual exposure values for each projection
image included in the examination. PURPOSE: To investigate the error in resulting
effective dose introduced by not using individual exposure values for each
projection image in the dose calculations for 3D rotational imaging with
interventional fluoroscopy systems. MATERIAL AND METHODS: An interventional
fluoroscopy system was used to acquire images of two anthropomorphic phantoms.
Calculations of the effective dose were performed using two different methods: 1,
using individual exposure values for each projection image; and 2, using the mean
tube voltage and the total dose-area product (DAP), evenly distributed over a
selection of projection images. The second method was also tested in hypothetical
examinations to investigate the effects of worst-case scenarios regarding the
effect of exposure asymmetry on the error. RESULTS: The error in resulting
effective dose obtained when simplifying the dose calculations by using Method 2
instead of Method 1 was within +/-14%. The error increased slightly for the worst
case scenarios but was still smaller than +/-20%, regardless of anatomical
region, tube voltage variation, and patient size. CONCLUSION: Given the
uncertainties associated with the effective dose concept as well as of reported
DAP values, the present study indicates that dose calculations based on average
exposure values distributed over a smaller selection of projection angles can
provide reasonably accurate estimations of the radiation doses from 3D imaging
using interventional fluoroscopy systems.
PMID- 25852193
TI - Computed tomography in trauma patients using iterative reconstruction: reducing
radiation exposure without loss of image quality.
AB - BACKGROUND: Rising numbers of computed tomography (CT) examinations worldwide
have led to a focus on dose reduction in the latest developments in CT
technology. Iterative reconstruction (IR) models bear the potential to
effectively reduce dose while maintaining adequate image quality. PURPOSE: To
assess the impact of adaptive statistical iterative reconstruction (ASIR)
technique on dose reduction and image quality in a dedicated whole body CT (WBCT)
protocol for trauma patients. MATERIAL AND METHODS: A total of 122 subjects with
multiple trauma was prospectively included in our study. Subjects who had to
undergo a WBCT following a severe trauma were randomly assigned to two different
groups: Group A was examined with an ASIR protocol for the body series (n = 64),
group B (n = 58) was examined using a standard filtered back projection (FBP)
protocol. Image quality was assessed both quantitatively by calculating signal-to
noise ratio (SNR) and contrast-to-noise ratios (CNRs) and qualitatively by two
observers who evaluated image quality using a 5-point scale system. Applied dose
was analyzed as CTDIvol (mGy), total DLP (mGyxcm), and effective dose (mSv).
RESULTS: Applied dose for the body series in group A was about 23% lower than in
group B (P < 0.05). SNR and CNRs for different tissues were not significantly
different. Subjective image quality ratings were excellent and showed no
significant difference, with a high inter-reader agreement. CONCLUSION: ASIR
contributes to a relevant dose reduction without any loss of image quality in a
dedicated WBCT protocol for patients with multiple trauma.
PMID- 25852195
TI - Lack of genetic association between TREM2 and Alzheimer's disease in East Asian
population: a systematic review and meta-analysis.
AB - PURPOSE: Large-scale genome-wide association studies have identified TREM2
variants to be significantly associated with Alzheimer's disease (AD) in
caucasian population. The goal of this systematic study and meta-analysis was to
assess the association between Triggering receptor expressed on myeloid cells 2
(TREM2) variants and AD in East Asian population. METHODS: In this study,
literatures were searched in PubMed, MEDLINE, EMBASE, and the Cochrane library to
screen citations from January 1990 to June 2014. Data analysis was done by using
the Stata 12 software. RESULTS: Twelve studies were considered for analysis. A
total of 13 535 patients with AD and 22 976 healthy controls were studied. The
results showed that rs75932628 variant was significantly associated with AD in
caucasian population (P < .001, odds ratio 1/4 3.17, 95% confidence interval 2.45
4.09). However, the association was not found in East Asian population.
CONCLUSION: In our study, we found that TREM2 variant is likely not associated
with AD in East Asian population.
PMID- 25852196
TI - Developing peer review.
PMID- 25852197
TI - Lysophosphatidic acid signalling in development.
AB - Lysophosphatidic acid (LPA) is a bioactive phospholipid that is present in all
tissues examined to date. LPA signals extracellularly via cognate G protein
coupled receptors to mediate cellular processes such as survival, proliferation,
differentiation, migration, adhesion and morphology. These LPA-influenced
processes impact many aspects of organismal development. In particular, LPA
signalling has been shown to affect fertility and reproduction, formation of the
nervous system, and development of the vasculature. Here and in the accompanying
poster, we review the developmentally related features of LPA signalling.
PMID- 25852198
TI - Dynamic stem cell heterogeneity.
AB - Recent lineage-tracing studies based on inducible genetic labelling have
emphasized a crucial role for stochasticity in the maintenance and regeneration
of cycling adult tissues. These studies have revealed that stem cells are
frequently lost through differentiation and that this is compensated for by the
duplication of neighbours, leading to the consolidation of clonal diversity.
Through the combination of long-term lineage-tracing assays with short-term in
vivo live imaging, the cellular basis of this stochastic stem cell loss and
replacement has begun to be resolved. With a focus on mammalian spermatogenesis,
intestinal maintenance and the hair cycle, we review the role of dynamic
heterogeneity in the regulation of adult stem cell populations.
PMID- 25852199
TI - Glucagon is essential for alpha cell transdifferentiation and beta cell
neogenesis.
AB - The interconversion of cell lineages via transdifferentiation is an adaptive mode
of tissue regeneration and an appealing therapeutic target. However, its clinical
exploitation is contingent upon the discovery of contextual regulators of cell
fate acquisition and maintenance. In murine models of diabetes, glucagon
secreting alpha cells transdifferentiate into insulin-secreting beta cells
following targeted beta cell depletion, regenerating the form and function of the
pancreatic islet. However, the molecular triggers of this mode of regeneration
are unknown. Here, using lineage-tracing assays in a transgenic zebrafish model
of beta cell ablation, we demonstrate conserved plasticity of alpha cells during
islet regeneration. In addition, we show that glucagon expression is upregulated
after injury. Through gene knockdown and rescue approaches, we also find that
peptides derived from the glucagon gene are necessary for alpha-to-beta cell fate
switching. Importantly, whereas beta cell neogenesis was stimulated by glucose,
alpha-to-beta cell conversion was not, suggesting that transdifferentiation is
not mediated by glucagon/GLP-1 control of hepatic glucose production. Overall,
this study supports the hypothesis that alpha cells are an endogenous reservoir
of potential new beta cells. It further reveals that glucagon plays an important
role in maintaining endocrine cell homeostasis through feedback mechanisms that
govern cell fate stability.
PMID- 25852200
TI - Genome-wide identification of phospho-regulators of Wnt signaling in Drosophila.
AB - Evolutionarily conserved intercellular signaling pathways regulate embryonic
development and adult tissue homeostasis in metazoans. The precise control of the
state and amplitude of signaling pathways is achieved in part through the kinase-
and phosphatase-mediated reversible phosphorylation of proteins. In this study,
we performed a genome-wide in vivo RNAi screen for kinases and phosphatases that
regulate the Wnt pathway under physiological conditions in the Drosophila wing
disc. Our analyses have identified 54 high-confidence kinases and phosphatases
capable of modulating the Wnt pathway, including 22 novel regulators. These
candidates were also assayed for a role in the Notch pathway, and numerous
phospho-regulators were identified. Additionally, each regulator of the Wnt
pathway was evaluated in the wing disc for its ability to affect the
mechanistically similar Hedgehog pathway. We identified 29 dual regulators that
have the same effect on the Wnt and Hedgehog pathways. As proof of principle, we
established that Cdc37 and Gilgamesh/CK1gamma inhibit and promote signaling,
respectively, by functioning at analogous levels of these pathways in both
Drosophila and mammalian cells. The Wnt and Hedgehog pathways function in tandem
in multiple developmental contexts, and the identification of several shared
phospho-regulators serve as potential nodes of control under conditions of
aberrant signaling and disease.
PMID- 25852201
TI - The Rac1 regulator ELMO controls basal body migration and docking in
multiciliated cells through interaction with Ezrin.
PMID- 25852202
TI - Japanese Bereaved Family Members' Perspectives of Palliative Care Units and
Palliative Care: J-HOPE Study Results.
AB - The study purpose was to understand the perspectives of bereaved family members
regarding palliative care unit (PCU) and palliative care and to compare
perceptions of PCU before admission and after bereavement. A cross-sectional
questionnaire survey was conducted, and the perceptions of 454 and 424 bereaved
family members were obtained regarding PCU and palliative care, respectively.
Family members were significantly more likely to have positive perceptions after
bereavement (ranging from 73% to 80%) compared to before admission (ranging from
62% to 71%). Bereaved family members who were satisfied with medical care in the
PCU had a positive perception of the PCU and palliative care after bereavement.
Respondents younger than 65 years of age were significantly more likely to have
negative perceptions of PCU and palliative care.
PMID- 25852203
TI - Is There a Need for Early Palliative Care in Patients With Life-Limiting
Illnesses? Interview Study With Patients About Experienced Care Needs From
Diagnosis Onward.
AB - The early integration of specialist palliative care has been shown to benefit the
quality of life of patients with advanced cancer. In order to explore whether
other seriously ill people and people at even earlier phases would also benefit
from early palliative care, we conducted 18 qualitative interviews with people
having cancer, chronic obstructive lung disease, heart failure, or dementia at
different phases of the illness trajectory about how they experienced care needs
related to their disease from diagnosis onward. Respondents experienced needs
within the different domains of palliative care at different stages of the
illness and different illness types or duration of the illness. This study
contributes to the understanding of primary care needs of patients for whom
palliative care (not necessarily specialized palliative care) could be
beneficial.
PMID- 25852204
TI - Improving Diabetes Care for Hospice Patients.
AB - Although type 2 diabetes guidelines recommend less aggressive glycemic control
for patients with limited life expectancy, many hospice patients continue their
glucose-lowering medications, resulting in an increased risk of hypoglycemia.
Three common reasons for overly tight glycemic control in hospice patients
include (1) discussions about reducing or stopping chronic medications are
uncomfortable; (2) many patients and families believe that mild hyperglycemia can
cause symptoms; and (3) until 2014, Healthcare Information and Data Information
Set (HEDIS) quality indicators for glycemic control included hospice patients. To
address these issues, we recommend (1) providers discuss with patients and
families upon hospice enrollment that diabetes medications can be reduced or
discontinued as their life-limiting disease progresses; (2) keeping blood glucose
levels between 200 and 300 mg/dL; and (3) educate providers that HEDIS measures
now exclude hospice patients. Implementing these recommendations should decrease
the risk of hypoglycemia in hospice patients and improve their quality of life.
PMID- 25852205
TI - Prevalence of and Racial Disparities in Risk Factor Control in Older Adults With
Diabetes: The Atherosclerosis Risk in Communities Study.
AB - OBJECTIVE: Controversy surrounds appropriate risk factor targets in older adults
with diabetes. We evaluated the proportion of older adults with diabetes meeting
different targets, focusing on possible differences by race, and assessed whether
demographic and clinical characteristics explained disparities. RESEARCH DESIGN
AND METHODS: We conducted a cross-sectional study of 5,018 participants aged 67
90 years (1,574 with and 3,444 without diagnosed diabetes) who attended visit 5
of the Atherosclerosis Risk in Communities (ARIC) study (2011-2013). Risk factor
targets were defined using both stringent (and less stringent) goals: hemoglobin
A1c (HbA1c) <7%, <53 mmol/mol (<8%, <64 mmol/mol); LDL cholesterol (LDL-c) <100
mg/dL (<130 mg/dL); and blood pressure (BP) <140/90 mmHg (<150/90 mmHg). We used
Poisson regression to obtain prevalence ratios (PRs). RESULTS: Most older adults
with diabetes met stringent (and less stringent) targets: 72% (90%) for HbA1c,
63% (86%) for LDL-c, and 73% (87%) for BP; but only 35% (68%) met all three. A
higher proportion of whites than blacks met targets, however defined. Among
people treated for risk factors, racial disparities in prevalence of meeting
stringent targets persisted even after adjustment: PRs (whites vs. blacks) were
1.03 (95% CI 0.91, 1.17) for HbA1c, 1.21 (1.09, 1.35) for LDL-c, 1.10 (1.00,
1.21) for BP, and 1.28 (0.99, 1.66) for all three. Results were similar but
slightly attenuated using less stringent goals. Black women were less likely than
white women to meet targets for BP and all three risk factors; this disparity was
not observed in men. CONCLUSIONS: Black-white disparities in risk factor control
in older adults with diabetes were not fully explained by demographic or clinical
characteristics and were greater in women than men. Further study of determinants
of these disparities is important.
PMID- 25852207
TI - Prevalence of Prediabetes and Undiagnosed Diabetes in Canada (2007-2011)
According to Fasting Plasma Glucose and HbA1c Screening Criteria.
AB - OBJECTIVE: To provide the first population-based estimates of prediabetes and
undiagnosed type 2 diabetes prevalence in Canada. RESEARCH DESIGN AND METHODS: We
combined two fasting subsamples of the Canadian Health Measures Survey, which
were restricted to nonpregnant adults >=20 years of age (N = 3,494). Undiagnosed
diabetes was defined as not having self-reported type 2 diabetes but having blood
glucose measures that met Canadian guidelines (i.e., fasting plasma glucose [FPG]
level of >=7.0 mmol/L or hemoglobin A1c [HbA1c] level of >=6.5% [>=48 mmol/mol]).
Prediabetes was defined as an FPG level of >=6.1 and <7.0 mmol/L or an HbA1c
level of >=6.0% and <6.5% (>=42 and <48 mmol/mol). All estimates were weighted
using survey sampling weights. CIs were calculated with the bootstrap method.
RESULTS: According to FPG levels, the prevalence of undiagnosed type 2 diabetes
in Canadian adults was 1.13% (95% CI 0.79, 1.62), contributing to ~20% of total
type 2 diabetes prevalence (5.62 [95% CI 4.52, 6.95]). Compared with FPG levels,
the undiagnosed prevalence was greater using HbA1c level as a criterion (3.09%
[95% CI 1.97, 4.81]), ~41% of the total number of cases of diabetes (7.55 [95% CI
5.98, 9.49]). The HbA1c-only criterion resulted in a threefold increase in
prediabetes prevalence overall and a sixfold increase among females (FPG 2.22%,
HbA1c 13.31%). Screening based on FPG only identified older undiagnosed case
patients, with a mean age of 58.7 years (95% CI 59.9, 63.4). Similarly, using
HbA1c identified younger individuals with prediabetes, with reduced BMI and waist
circumference compared with FPG levels. CONCLUSIONS: In this first study of a
nationally representative sample with biospecimen measures, we found that the
prevalence of undiagnosed type 2 diabetes and prediabetes was significantly
higher using HbA1c levels compared with FPG levels. Further evaluation is needed
to fully assess the impact of using the HbA1c criterion.
PMID- 25852206
TI - Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity
in Insulin-Resistant Humans.
AB - OBJECTIVE: Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and
stimulate mitochondrial biogenesis in rodents, but the findings of translational
studies in humans are thus far ambiguous. The aim of this study was to evaluate
the influence of EPA and DHA on insulin sensitivity, insulin secretion, and
muscle mitochondrial function in insulin-resistant, nondiabetic humans using a
robust study design and gold-standard measurements. RESEARCH DESIGN AND METHODS:
Thirty-one insulin-resistant adults received 3.9 g/day EPA+DHA or placebo for 6
months in a randomized double-blind study. Hyperinsulinemic-euglycemic clamp with
somatostatin was used to assess hepatic and peripheral insulin sensitivity.
Postprandial glucose disposal and insulin secretion were measured after a meal.
Measurements were performed at baseline and after 6 months of treatment.
Abdominal fat distribution was evaluated by MRI. Muscle oxidative capacity was
measured in isolated mitochondria using high-resolution respirometry and
noninvasively by magnetic resonance spectroscopy. RESULTS: Compared with placebo,
EPA+DHA did not alter peripheral insulin sensitivity, postprandial glucose
disposal, or insulin secretion. Hepatic insulin sensitivity, determined from the
suppression of endogenous glucose production by insulin, exhibited a small but
significant improvement with EPA+DHA compared with placebo. Muscle mitochondrial
function was unchanged by EPA+DHA or placebo. CONCLUSIONS: This study
demonstrates that dietary EPA+DHA does not improve peripheral glucose disposal,
insulin secretion, or skeletal muscle mitochondrial function in insulin-resistant
nondiabetic humans. There was a modest improvement in hepatic insulin sensitivity
with EPA+DHA, but this was not associated with any improvements in clinically
meaningful outcomes.
PMID- 25852208
TI - Dapagliflozin's Effects on Glycemia and Cardiovascular Risk Factors in High-Risk
Patients With Type 2 Diabetes: A 24-Week, Multicenter, Randomized, Double-Blind,
Placebo-Controlled Study With a 28-Week Extension.
AB - OBJECTIVE: To assess the efficacy and safety of dapagliflozin, a selective sodium
glucose cotransporter 2 inhibitor, compared with placebo in patients with type 2
diabetes (T2D), documented pre-existing cardiovascular disease (CVD), and a
history of hypertension. RESEARCH DESIGN AND METHODS: Patients (N = 922) were
randomized to receive 10 mg dapagliflozin or placebo in a double-blind trial for
24 weeks, followed by a 28-week extension period. In patients receiving insulin,
the insulin dose was reduced by 25% at randomization. Patients were stratified by
age, insulin use, and time from the most recent qualifying cardiovascular (CV)
event. Co-primary end points were a change from baseline in hemoglobin A1c
(HbA1c) and the proportion of patients achieving a combined reduction in HbA1c of
>=0.5% (5.5 mmol/mol), body weight (BW) of >=3%, and systolic blood pressure
(SBP) of >=3 mmHg. RESULTS: At 24 weeks, dapagliflozin significantly reduced
HbA1c (-0.38% [-4.2 mmol/mol]) from baseline (8.18%) compared with a slight
increase with placebo from baseline (8.08%) (0.08% [0.9 mmol/mol]). Significantly
more patients met the three-item end point with treatment with dapagliflozin than
with placebo (11.7% vs. 0.9%, respectively). Changes were maintained over 52
weeks. Although ~42% of patients were >=65 years old, similar results were
observed in both age-stratified groups. Serious adverse events, hypoglycemia,
urinary tract infections, and cardiac disorders were similar between groups.
Adverse events of hypotension, dehydration, hypovolemia, genital infection, and
renal failure or impairment occurred more often with dapagliflozin treatment.
CONCLUSIONS: In this study that evaluated T2D patients who were at high risk for
future CVD events, dapagliflozin administration had significantly greater effects
in reducing HbA1c, BW, and SBP, without adversely impacting CV safety when
compared with placebo treatment.
PMID- 25852209
TI - Genetic Predisposition to Central Obesity and Risk of Type 2 Diabetes: Two
Independent Cohort Studies.
AB - OBJECTIVE: Abdominal obesity is a major risk factor for type 2 diabetes (T2D). We
aimed to examine the association between the genetic predisposition to central
obesity, assessed by the waist-to-hip ratio (WHR) genetic score, and T2D risk.
RESEARCH DESIGN AND METHODS: The current study included 2,591 participants with
T2D and 3,052 participants without T2D of European ancestry from the Nurses'
Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Genetic
predisposition to central obesity was estimated using a genetic score based on 14
established loci for the WHR. RESULTS: We found that the central obesity genetic
score was linearly related to higher T2D risk. Results were similar in the NHS
(women) and HPFS (men). In combined results, each point of the central obesity
genetic score was associated with an odds ratio (OR) of 1.04 (95% CI 1.01-1.07)
for developing T2D, and the OR was 1.24 (1.03-1.45) when comparing extreme
quartiles of the genetic score after multivariate adjustment. CONCLUSIONS: The
data indicate that genetic predisposition to central obesity is associated with
higher T2D risk. This association is mediated by central obesity.
PMID- 25852210
TI - Longitudinal Association Between Endothelial Dysfunction, Inflammation, and
Clotting Biomarkers With Subclinical Atherosclerosis in Type 1 Diabetes: An
Evaluation of the DCCT/EDIC Cohort.
AB - OBJECTIVE: There is considerable interest in identifying biomarkers that predict
high risk for the development of macrovascular complications in patients with
diabetes. Therefore, the longitudinal association between subclinical
atherosclerosis as measured by internal carotid artery intima-media thickness
(IMT) and acute-phase reactants, cytokines/adipokines, thrombosis, and adhesion
molecules was examined. RESEARCH DESIGN AND METHODS: Biomarkers were measured at
four time points over 20 years in 886 DCCT/EDIC participants with type 1
diabetes. Four composite scores were created by combining z scores generated from
within the data set of individual biomarkers: acute-phase reactants (fibrinogen,
C-reactive protein), thrombosis (fibrinogen, active and total plasminogen
activator inhibitor [PAI]-1), cytokines/adipokines (tumor necrosis factor
receptor-1 and -2, active and total PAI-1, IL-6), and endothelial dysfunction
(soluble intracellular adhesion molecule-1, soluble vascular cell adhesion
molecule-1, and soluble E-selectin). Internal carotid IMT was measured at EDIC
years 1, 6, and 12, with elevated IMT defined at each time point as being in the
upper quintile of its distribution. RESULTS: Logistic regression models indicate
that while individual biomarkers were not predictive of or associated with
subclinical atherosclerosis, composite scores of acute-phase reactants (odds
ratio [OR] 2.78 [95% CI 1.42, 5.42]), thrombolytic factors (OR 2.83 [95% CI 1.45,
5.52]), and cytokines/adipokines (OR 2.83 [95% CI 1.48, 5.41]) measured at our
final time point EDIC years 8-11 were associated with higher levels of
atherosclerosis at EDIC year 12, but findings were not consistent at early time
points. The endothelial dysfunction score was not appreciably predictive of or
associated with subclinical atherosclerosis at any of the time points measured.
CONCLUSIONS: The pathophysiologic relationship between higher biomarker levels
and progression of subclinical atherosclerosis remains unclear.
PMID- 25852211
TI - Platelet-to-Lymphocyte Ratio Predicts Contrast-Induced Nephropathy in Patients
With Non-ST-Segment Elevation Acute Coronary Syndrome.
AB - We assessed the relation between platelet-to-lymphocyte ratio (PLR) on admission
and contrast-induced nephropathy (CIN) in patients with non-ST-segment elevation
acute coronary syndrome (NSTE-ACS). A total of 488 patients with NSTE-ACS who
underwent urgent coronary angiography were enrolled. Levels of PLR and creatinine
were measured before angiography and at 72 hours after angiography. Patients were
divided into 2 groups, namely, the CIN group, 80 patients (16.3%; age 65.3 +/-
12.5years; 66.7% men) and the non-CIN group, 408 patients (83.7%; age 61.2 +/-
12.3 years; 72.5% men). Patients in the CIN group had significantly higher PLR
than those in the non-CIN group (152.9 +/- 99.6 vs 120.4 +/- 66.1, P < .001). In
logistic regression analysis, PLR (odds ratio [OR] 1.004, 95% confidence interval
[CI] 1.001-1.007, P = .02), diabetes mellitus (OR 1.75, 95% CI 1.02-2.98, P =
.03), and ST-segment depression on admission electrocardiogram (OR 1.68, 95% CI
1.00-2.81, P = .04) were independent predictors of CIN. The PLR was an
independent predictor of CIN after angiography in patients with NSTE-ACS.
PMID- 25852212
TI - Importance of Uric Acid Levels and Comorbidities Affecting Renal Function.
PMID- 25852213
TI - Microbiome Disturbances and Autism Spectrum Disorders.
AB - Autism spectrum disorders (ASDs) are considered a heterogenous set of
neurobehavioral diseases, with the rates of diagnosis dramatically increasing in
the past few decades. As genetics alone does not explain the underlying cause in
many cases, attention has turned to environmental factors as potential
etiological agents. Gastrointestinal disorders are a common comorbidity in ASD
patients. It was thus hypothesized that a gut-brain link may account for some
autistic cases. With the characterization of the human microbiome, this concept
has been expanded to include the microbiota-gut-brain axis. There are mounting
reports in animal models and human epidemiologic studies linking disruptive
alterations in the gut microbiota or dysbiosis and ASD symptomology. In this
review, we will explore the current evidence that gut dysbiosis in animal models
and ASD patients correlates with disease risk and severity. The studies to date
have surveyed how gut microbiome changes may affect these neurobehavioral
disorders. However, we harbor other microbiomes in the body that might impact
brain function. We will consider microbial colonies residing in the oral cavity,
vagina, and the most recently discovered one in the placenta. Based on the
premise that gut microbiota alterations may be causative agents in ASD, several
therapeutic options have been tested, such as diet modulations, prebiotics,
probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and
activated charcoal. The potential benefits of these therapies will be considered.
Finally, the possible mechanisms by which changes in the gut bacterial
communities may result in ASD and related neurobehavioral disorders will be
examined.
PMID- 25852214
TI - In situ simulation as a quality improvement initiative.
AB - Simulation-based learning has gained recent recognition as a means of improving
patient safety. In situ simulation, that is conducting simulation training in
actual clinical environment, is a novel approach to detecting deficiencies in
healthcare systems, termed as latent safety threats (LSTs). We implemented in
situ simulation training as a quality improvement initiative and were able to
detect several LSTs, thus improving patient safety.
PMID- 25852215
TI - A rare case of left internal mammary artery disease before bypass surgery.
PMID- 25852216
TI - Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta
analysis of prospective observational studies.
AB - BACKGROUND: Whether orthostatic hypotension (OH) is a risk factor for
cardiovascular morbidity and death is uncertain. Currently available evidence
derives from non-homogeneous and partly ambiguous studies. OBJECTIVE: We aimed at
assessing the relationship between OH and death or major adverse cardiac and
cerebrovascular events (MACCEs) by integrating results of previous studies.
METHODS: We performed a meta-analysis of prospective observational studies
reporting on the association between prevalent OH, mortality, and incident MACCE,
published from 1966 through 2013. Mantel-Haenszel pooled estimates of relative
risk (RR) and 95% confidence intervals (CIs) for all-cause death were assessed as
the primary endpoint at the longest follow-up; incident coronary heart disease
(CHD), heart failure (HF), and stroke were assessed as secondary endpoints. We
also performed post hoc subgroup analyses stratified by age and a meta-regression
analysis. RESULTS: We identified a total of 13 studies, including an overall
population of 121 913 patients, with a median follow-up of 6 years. Compared with
the absence of OH, the occurrence of OH was associated with a significantly
increased risk of all-cause death (RR 1.50; 95% CI 1.24-1.81), incident CHD (RR
1.41; 95% CI 1.22-1.63), HF (RR 2.25; 95% CI 1.52-3.33), and stroke (RR 1.64; 95%
CI 1.13-2.37). When analysed according to age, pooled estimates of RR (95% CI)
for all-cause death were 1.78 (1.25-2.52) for patients <65 years old, and 1.26
(0.99-1.62) in the older subgroup. CONCLUSION: Orthostatic hypotension is
associated with a significantly increased risk of all-cause death, incident CHD,
HF, and stroke.
PMID- 25852217
TI - When everything is not everywhere but species evolve: an alternative method to
model adaptive properties of marine ecosystems.
AB - The functional and taxonomic biogeography of marine microbial systems reflects
the current state of an evolving system. Current models of marine microbial
systems and biogeochemical cycles do not reflect this fundamental organizing
principle. Here, we investigate the evolutionary adaptive potential of marine
microbial systems under environmental change and introduce explicit Darwinian
adaptation into an ocean modelling framework, simulating evolving phytoplankton
communities in space and time. To this end, we adopt tools from adaptive dynamics
theory, evaluating the fitness of invading mutants over annual timescales,
replacing the resident if a fitter mutant arises. Using the evolutionary
framework, we examine how community assembly, specifically the emergence of
phytoplankton cell size diversity, reflects the combined effects of bottom-up and
top-down controls. When compared with a species-selection approach, based on the
paradigm that "Everything is everywhere, but the environment selects", we show
that (i) the selected optimal trait values are similar; (ii) the patterns
emerging from the adaptive model are more robust, but (iii) the two methods lead
to different predictions in terms of emergent diversity. We demonstrate that
explicitly evolutionary approaches to modelling marine microbial populations and
functionality are feasible and practical in time-varying, space-resolving
settings and provide a new tool for exploring evolutionary interactions on a
range of timescales in the ocean.
PMID- 25852218
TI - Serum creatinine level: a supplemental index to distinguish Duchenne muscular
dystrophy from Becker muscular dystrophy.
AB - BACKGROUND: To improve assessment of dystrophinopathy, the aim of this study was
to identify whether serum creatinine (Crn) level reflects disease severity.
METHODS: Biochemical, Vignos score, and genetic data were collected on 212 boys
with dystrophinopathy. RESULTS: Serum Crn level had a strong inverse correlation
with Vignos score by simple correlation (r = -0.793) and partial correlation
analysis after adjustment for age, height, and weight (r = -0.791; both P <
0.01). Serum Crn level was significantly higher in patients with in-frame than
out-of-frame mutations (Z = -4.716, P < 0.01) and in Becker muscular dystrophy
(BMD) patients than Duchenne muscular dystrophy (DMD) patients at ages 4, 5, 7,
and 9 yr (all P < 0.0125). After adjusting for age, height, and weight, BMD
patients still had a significantly higher serum Crn level than DMD patients (beta
= 7.140, t = 6.277, P < 0.01). CONCLUSIONS: Serum Crn level reflected disease
severity and may serve as a supplemental index to distinguish DMD from BMD in
clinical practice.
PMID- 25852219
TI - Vascular effects of advanced glycation end-products: content of
immunohistochemically detected AGEs in radial artery samples as a predictor for
arterial calcification and cardiovascular risk in asymptomatic patients with
chronic kidney disease.
AB - OBJECTIVES: Our aim was to determine whether vascular deposition of advanced
glycation end-products (AGEs) is associated with arterial calcification and
cardiovascular mortality in chronic kidney disease (CKD) patients and to assess
the relationships between vascular content of AGEs and selected clinical and
biochemical parameters. MATERIALS AND METHODS: The study comprised 54 CKD
patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI,
incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs
and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein
(hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of
radial artery obtained during creation of hemodialysis access were stained for
calcifications using alizarin red. AGEs deposits were identified
immunohistochemically and their relative content was quantified. RESULTS:
Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI
1, and DPPH scavenging in simple regression; only fetuin-A was an independent
predictor in multiple regression. There was a significant positive trend in the
intensity of AGEs immunostaining among patients with grades 1, 2, and 3
calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular
mortality irrespective of patient's age. CONCLUSIONS: The present study
demonstrates an involvement of AGEs in the development of medial arterial
calcification and the impact of arterial AGE deposition on cardiovascular
mortality in CKD patients.
PMID- 25852220
TI - The apolipoprotein B/apolipoprotein A-I ratio as a potential marker of plasma
atherogenicity.
AB - BACKGROUND: The apolipoprotein (apo) B/apoA-I ratio represents the balance
between apoB-rich atherogenic particles and apoA-I-rich antiatherogenic
particles, and this ratio is considered to be a marker of cardiovascular risk.
Although many studies have demonstrated the importance of the apoB/apoA-I ratio
in predicting the presence or absence of cardiovascular disease, less is known
about apoB/apoA-I ratio as a marker of plasma atherogenicity. METHODS: A total of
157 normolipidemic men aged 20-59 years were included in the study. The plasma
levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein
cholesterol (HDL-C), apoA-I, apoB, and apoE were determined after a 12 h fasting
period. RESULTS: The median of the apoB/apoA-I ratio in the studied
normolipidemic subjects was 0.52, with values ranging from 0.19 to 2.60. The
percentage of subjects with the apoB/apoA-I ratio exceeding 0.9 (the accepted
risk value of cardiovascular disease) was 19.1%. The subjects with apoB/apoA
I>0.9 were characterized by higher TG levels and atherogenic index of plasma
(AIP) and lower values of ratio of low-density lipoprotein cholesterol (LDL-C) to
apoB (LDL-C/apoB) and apoE levels compared with men with apoB/apoA-I<0.9.
CONCLUSION: Despite normolipidemia, the subjects with the unfavorable apoB/apoA-I
ratio had more atherogenic lipid profile.
PMID- 25852221
TI - Procalcitonin levels in gram-positive, gram-negative, and fungal bloodstream
infections.
AB - Procalcitonin (PCT) can discriminate bacterial from viral systemic infections and
true bacteremia from contaminated blood cultures. The aim of this study was to
evaluate PCT diagnostic accuracy in discriminating Gram-positive, Gram-negative,
and fungal bloodstream infections. A total of 1,949 samples from patients with
suspected bloodstream infections were included in the study. Median PCT value in
Gram-negative (13.8 ng/mL, interquartile range (IQR) 3.4-44.1) bacteremias was
significantly higher than in Gram-positive (2.1 ng/mL, IQR 0.6-7.6) or fungal
(0.5 ng/mL, IQR 0.4-1) infections (P < 0.0001). Receiver operating characteristic
analysis showed an area under the curve (AUC) for PCT of 0.765 (95% CI 0.725
0.805, P < 0.0001) in discriminating Gram-negatives from Gram-positives at the
best cut-off value of 10.8 ng/mL and an AUC of 0.944 (95% CI 0.919-0.969, P <
0.0001) in discriminating Gram-negatives from fungi at the best cut-off of 1.6
ng/mL. Additional results showed a significant difference in median PCT values
between Enterobacteriaceae and nonfermentative Gram-negative bacteria (17.1
ng/mL, IQR 5.9-48.5 versus 3.5 ng/mL, IQR 0.8-21.5; P < 0.0001). This study
suggests that PCT may be of value to distinguish Gram-negative from Gram-positive
and fungal bloodstream infections. Nevertheless, its utility to predict different
microorganisms needs to be assessed in further studies.
PMID- 25852222
TI - Immunohistochemical expression of nuclear factor erythroid-2-related factor 2 and
heme oxygenase 1 in normal bovine lung and bovine lung infected with Mannheimia
haemolytica.
AB - Mannheimia haemolytica is an important cause of pneumonia in feedlot cattle.
Nuclear factor erythroid-2-related factor 2 (Nrf2) is a redox-sensitive
transcription factor responsible for the induction of antioxidant enzymes, such
as heme oxygenase 1 (HO-1), within the lung. The expression of Nrf2 and HO-1 was
immunohistochemically evaluated in 4 calves 24 h after experimental infection
with M. haemolytica. Calves receiving normal saline served as controls. In the
infected lungs, cytoplasmic Nrf2 expression was high in macrophages and
bronchioles and low in alveolar epithelium, whereas nuclear expression was high
in endothelial cells, macrophages, and bronchioles and lowest in alveolar
epithelium. Normal lung samples displayed only faint Nrf2 cytoplasmic staining
within bronchiolar epithelium. Expression of HO-1 was detected within the
cytoplasm of macrophages and bronchiolar epithelial cells in all infected lung
samples, whereas normal lungs displayed only weak cytoplasmic staining in
bronchiolar epithelial cells. These findings suggest that bronchiolar epithelial
cells and macrophages up-regulate Nrf2 expression early in the course of
infection, which results in increased expression of HO-1 within these cells.
PMID- 25852223
TI - Avian reovirus replication in mononuclear phagocytes in chicken footpad and
spleen after footpad inoculation.
AB - Circulating monocytes and tissue macrophages were suggested to be susceptible to
avian reovirus (ARV) infection. To determine if ARV infects and replicates in
mononuclear phagocytes (KUL01-positive cells), we infected 3-day-old specific
pathogen-free chickens with ARV strain 2408 by inoculation of the left footpad.
The left footpads and spleens were collected for analysis at 1.5 and 2.5 d after
inoculation. Replication of ARV in the footpad and spleen was demonstrated by
detection of the viral protein sigmaNS using immunohistochemical testing and
viral S1 RNA expression by real-time quantitative polymerase chain reaction
(qPCR). Furthermore, immunofluorescent double-staining assay of cytocentrifuged
cells and cryosections of the footpad and spleen for the viral protein sigmaNS
and the surface marker recognized by monoclonal antibody (MAb) KUL01 indicated
that KUL01-positive cells costained with MAb H1E1, which recognizes ARV protein
sigmaNS. In addition, more ARV S1 RNA was measured by qPCR in the KUL01-positive
cell samples prepared from the footpad or spleen 1.5 d after inoculation compared
with non-KUL01-positive cell samples. The amounts of ARV S1 RNA in the spleen
were significantly lower (P < 0.05) than the amounts in the footpad 1.5 d after
inoculation. The results suggest that ARV infects mononuclear phagocytes and then
replicates within these cells before migrating to the spleen, where it infects
and replicates in KUL01-positive cells.
PMID- 25852224
TI - The anesthetic interaction of propofol and sevoflurane on the minimum alveolar
concentration preventing motor movement (MACNM) in dogs.
AB - The objective of this study was to determine the effects of propofol on the
minimum alveolar concentration of sevoflurane needed to prevent motor movement
(MAC(NM)) in dogs subjected to a noxious stimulus using randomized crossover
design. Six, healthy, adult beagles (9.2 +/- 1.3 kg) were used. Dogs were
anesthetized with sevoflurane on 3 occasions, at weekly intervals, and baseline
MAC(NM) (MAC(NM-B)) was determined on each occasion. Propofol treatments were
administered as loading dose (LD) and constant rate infusion (CRI) as follows:
Treatment 1 (T1) was 2 mg/kg body weight (BW) and 4.5 mg/kg BW per hour; T2 was 4
mg/kg BW and 9 mg/kg BW per hour; T3 was 8 mg/kg BW and 18 mg/kg BW per hour,
respectively. Treatment MAC(NM) (MAC(NM-T)) determination was initiated 60 min
after the start of the CRI. Two venous blood samples were collected and combined
at each MAC(NM-T) determination for measurement of blood propofol concentration
using high-performance liquid chromatography method (HPLC). Data were analyzed
using a mixed-model ANOVA and are presented as least square means (LSM) +/-
standard error of means (SEM). Propofol infusions in the range of 4.5 to 18 mg/kg
BW per hour resulted in mean blood concentrations between 1.3 and 4.4 MUg/mL, and
decreased (P < 0.05) sevoflurane MAC(NM) in a concentration-dependent manner. The
percentage decrease in MAC(NM) was 20.5%, 43.0%, and 68.3%, with corresponding
blood propofol concentrations of 1.3 +/- 0.3 MUg/mL, 2.5 +/- 0.3 MUg/mL, and 4.4
+/- 0.3 MUg/mL, for T1, T2, and T3, respectively. Venous blood propofol
concentrations were strongly correlated (r = 0.855, P < 0.0001) with the decrease
in MAC(NM). In dogs, propofol decreased the sevoflurane MAC(NM) in a
concentration-dependent manner.
PMID- 25852225
TI - Osteogenic potential of sorted equine mesenchymal stem cell subpopulations.
AB - The objectives of this study were to use non-equilibrium gravitational field-flow
fractionation (GrFFF), an immunotag-less method of sorting mesenchymal stem cells
(MSCs), to sort equine muscle tissue-derived mesenchymal stem cells (MMSCs) and
bone marrow-derived mesenchymal stem cells (BMSC) into subpopulations and to
carry out assays in order to compare their osteogenic capabilities. Cells from 1
young adult horse were isolated from left semitendinosus muscle tissue and from
bone marrow aspirates of the fourth and fifth sternebrae. Aliquots of 800 * 10(3)
MSCs from each tissue source were sorted into 5 fractions using non-equilibrium
GrFFF (GrFFF proprietary system). Pooled fractions were cultured and expanded for
use in osteogenic assays, including flow cytometry, histochemistry, bone nodule
assays, and real-time quantitative polymerase chain reaction (qPCR) for gene
expression of osteocalcin (OCN), RUNX2, and osterix. Equine MMSCs and BMSCs were
consistently sorted into 5 fractions that remained viable for use in further
osteogenic assays. Statistical analysis confirmed strongly significant
upregulation of OCN, RUNX2, and osterix for the BMSC fraction 4 with P < 0.00001.
Flow cytometry revealed different cell size and granularity for BMSC fraction 4
and MMSC fraction 2 compared to unsorted controls and other fractions.
Histochemisty and bone nodule assays revealed positive staining nodules without
differences in average nodule area, perimeter, or stain intensity between tissues
or fractions. As there are different subpopulations of MSCs with different
osteogenic capacities within equine muscle- and bone marrow-derived sources,
these differences must be taken into account when using equine stem cell therapy
to induce bone healing in veterinary medicine.
PMID- 25852226
TI - The effect of dystocia on physiological and behavioral characteristics related to
vitality and passive transfer of immunoglobulins in newborn Holstein calves.
AB - The objective of this study was to examine the effect of calving difficulty or
dystocia on the vitality of newborn calves and its association with blood pH, the
apparent efficiency of immunoglobulin G (IgG) absorption (AEA), and weight gain.
A total of 45 calving events (N = 48 calves) were monitored from the first sight
of fetal membranes. All calves were assessed at the time of first attaining
sternal recumbency (SR), at 2 and 24 h, and at 7 and 14 d of age. Measurements
included time to SR, rectal temperature, respiration and heart rate, analysis of
blood gases and other blood measures, suckling response, time to standing,
passive transfer of IgG, and weight gain. Calves were separated from their dam 2
h after birth and fed a commercial colostrum replacer containing 180 g of IgG by
esophageal tube feeder. Calves born following dystocia had lower venous blood pH
and took longer to attain SR and attempt to stand than those born unassisted.
Duration of calving interacted with the number of people required to extract the
calf by pulling as a significant predictor of pH at SR. No association was found
between pH at SR and AEA. However, reduced AEA was found in calves that were
female and in calves that did not achieve SR within 15 min of birth. A longer
calving duration, being born in July or August rather than June, and a shorter
time spent standing in the first 2 d of life were significantly associated with
reduced weight gain to 14 d. It was concluded that factors at calving impact the
physiology, vitality, and subsequent weight gain of newborn calves.
PMID- 25852227
TI - Identification of Escherichia coli F4ac-binding proteins in porcine milk fat
globule membrane.
AB - F4ac-positive enterotoxigenic Escherichia coli (ETEC) must attach to the
intestinal mucosa to cause diarrhea in piglets. Prevention of bacterial
attachment to the intestinal mucosa is the most effective defense against ETEC
induced diarrhea. Porcine milk fat globule membranes (MFGM) were shown to be able
to inhibit attachment of ETEC to the intestinal brush border; however, the
specific components of porcine MFGM that inhibited attachment of ETEC to
enterocytes were not identified. Accordingly, the purpose of this study was to
identify F4ac-binding MFGM proteins by overlay Western blot and affinity
chromatography. The proteome of porcine MFGM was characterized and the following
F4ac-binding proteins were detected by overlay Western blot and affinity
chromatography: lactadherin, butyrophilin, adipophilin, acyl-CoA synthetase 3,
and fatty acid-binding protein 3. The biological function of these proteins was
not investigated but it is possible that their interaction with F4ac fimbria
interferes with bacterial attachment and colonization.
PMID- 25852228
TI - Staphylococcus spp., Streptococcus canis, and Arcanobacterium phocae of healthy
Canadian farmed mink and mink with pododermatitis.
AB - Pododermatitis is a disease of concern for mink breeders in Canada and worldwide,
as it causes discomfort and lowers the breeding rates on farms affected by the
disease. Unfortunately, the etiology and pathogenesis of pododermatitis are still
unknown. In this study, we compared Staphylococcus spp. and Streptococcus canis
isolates from healthy mink with isolates from animals with pododermatitis on 2
farms in Ontario. Almost all hemolytic Staphylococcus spp. isolated were shown to
be Staphylococcus delphini Group A by 16S ribosomal ribonucleic acid (rRNA)
sequence analysis and polymerase chain reaction (PCR). Pulsed-field gel
electrophoresis (PFGE) did not reveal any S. delphini or S. canis clonal lineages
specifically associated with pododermatitis, which suggests that these bacteria
do not act as primary pathogens, but does not dismiss their potential roles as
opportunistic pathogens. While S. delphini and S. canis were the most prevalent
bacterial pathogens in mink pododermatitis, they were also present in samples
from healthy mink. Arcanobacterium phocae is occasionally isolated from
pododermatitis cases, but is difficult to recover with conventional culture
methods due to its slow growth. A quantitative real-time PCR was developed for
the detection of A. phocae and was tested on 138 samples of footpad tissues from
14 farms. The bacterium was detected only in pododermatitis-endemic farms in
Canada and was at higher concentrations in tissues from infected footpads than in
healthy tissues. This finding suggests that A. phocae is involved in the
pathogenesis of pododermatitis.
PMID- 25852229
TI - Assessment of a correlation between Canine Atopic Dermatitis Extent and Severity
Index (CADESI-03) and selected biophysical skin measures (skin hydration, pH, and
erythema intensity) in dogs with naturally occurring atopic dermatitis.
AB - Atopic dermatitis is a common allergic skin disease in dogs. The aim of this
study was to examine the possibility of a correlation between biophysical skin
variables: skin hydration (SH), skin pH, and erythema intensity measured in 10
different body regions and both total Canine Atopic Dermatitis Extent and
Severity Index (CADESI-03) and CADESI measured in a given region (CADESI L). The
study was conducted using 33 dogs with atopic dermatitis. The assessment of the
biophysical variables was done in 10 body regions: the lumbar region, right
axillary fossa, right inguinal region, ventral abdominal region, right lateral
thorax region, internal surface of the auricle, interdigital region of right
forelimb, cheek, bridge of nose, and lateral site of antebrachum. Positive
correlations were found between SH and CADESI L for the following regions: the
inguinal region (r = 0.73) and the interdigital region (r = 0.82), as well as
between total CADESI and SH on digital region (r = 0.52). Also, positive
correlations were reported for skin pH and CADESI L in the lumbar region (r =
0.57), the right lateral thorax region (r = 0.40), and the lateral antebrachum (r
= 0.35). Positive correlations were found in the interdigital region between
erythema intensity and the total CADESI-03 (r = 0.60) as well as the CADESI L (r
= 0.7). The results obtained suggest that it may be possible to use skin
hydration, pH, and erythema intensity to assess the severity of skin lesion but
positive correlation was only found in < 13.3% of possible correlations and usage
of these measures in dogs is limited.
PMID- 25852230
TI - Role of the capsular polysaccharide as a virulence factor for Streptococcus suis
serotype 14.
AB - Streptococcus suis is an important swine pathogen and a zoonotic agent causing
meningitis and septicemia. Although serotype 2 is the most virulent type,
serotype 14 is emerging, and understanding of its pathogenesis is limited. To
study the role of the capsular polysaccharide (CPS) of serotype 14 as a virulence
factor, we constructed knockout mutants devoid of either cps14B, a highly
conserved regulatory gene, or neu14C, a gene coding for uridine diphospho-N
acetylglucosamine 2-epimerase, which is involved in sialic acid synthesis. The
mutants showed total loss of the CPS with coagglutination assays and electron
microscopy. Phagocytosis assays showed high susceptibility of mutant Deltacps14B.
An in vivo murine model was used to demonstrate attenuated virulence of this non
encapsulated mutant. Despite the difference in the CPS composition of different
serotypes, this study has demonstrated for the first time that the CPS of a
serotype other than 2 is also an important antiphagocytic factor and a critical
virulence factor.
PMID- 25852231
TI - Sequence and phylogenetic analysis of M-class genome segments of novel duck
reovirus NP03.
AB - We report the sequence and phylogenetic analysis of the entire M1, M2, and M3
genome segments of the novel duck reovirus (NDRV) NP03. Alignment between the
newly determined nucleotide sequences as well as their deduced amino acid
sequences and the published sequences of avian reovirus (ARV) was carried out
with DNASTAR software. Sequence comparison showed that the M2 gene had the most
variability among the M-class genes of DRV. Phylogenetic analysis of the M-class
genes of ARV strains revealed different lineages and clusters within DRVs. The 5
NDRV strains used in this study fall into a well-supported lineage that includes
chicken ARV strains, whereas Muscovy DRV (MDRV) strains are separate from NDRV
strains and form a distinct genetic lineage in the M2 gene tree. However, the
MDRV and NDRV strains are closely related and located in a common lineage in the
M1 and M3 gene trees, respectively.
PMID- 25852232
TI - Relationship between vaginal mucus conductivity and time of ovulation in weaned
sows.
AB - This study investigated whether changes in the vaginal electrical resistance
(VER) of vaginal mucus of weaned sows during the first 7 d post-weaning are
associated with time of ovulation. Time of ovulation was determined by ovarian
ultrasound carried out from 91 to 146 h after weaning and at different seasons.
Vaginal electrical resistance was measured at 20, 44, 68, 91, 96, 102, 115, 120,
126, 140, 146, and 164 h post-weaning and was found to decrease between 120 h and
31 h before ovulation and then increase until 40 to 50 h after ovulation.
Duration and timing of the nadir was affected by the season (P < 0.01). Estrus
was observed from day 4 after the lowest VER values. Ovulation occurred between
late day 5 and late day 6, while VER values were still increasing. Ovulation was
earlier in lower parity sows (P < 0.001). Compared to 0 h (ovulation time), VER
was significantly lower from 50 to 5 h before ovulation in autumn and from 40 to
21 h in winter, but such differences were not seen in spring. Lowest VER value
was not correlated with time of ovulation. It was concluded that VER increases
before ovulation and, although this increase is influenced by the season, it
cannot be used to accurately predict ovulation in weaned sows.
PMID- 25852233
TI - Equid herpesvirus 9 (EHV-9) isolates from zebras in Ontario, Canada, 1989 to
2007.
AB - The objective of this study was to identify and partially characterize 3 equid
herpesviruses that were isolated postmortem from zebras in Ontario, Canada in
1989, 2002, and 2007. These 3 virus isolates were characterized by plaque
morphology, restriction fragment length polymorphism (RFLP) of their genomic
deoxyribonucleic acid (DNA), real-time polymerase chain reaction (PCR) assay, and
sequence analyses of the full length of the glycoprotein G (gG) gene (ORF70) and
a portion of the DNA polymerase gene (ORF30). The isolates were also compared to
3 reference strains of equid herpesvirus 1 (EHV-1). Using rabbit kidney cells,
the plaques for the isolates from the zebras were found to be much larger in size
than the EHV-1 reference strains. The RFLP patterns of the zebra viruses differed
among each other and from those of the EHV-1 reference strains. Real-time PCR and
sequence analysis of a portion of the DNA polymerase gene determined that the
herpesvirus isolates from the zebras contained a G at nucleotide 2254 and a
corresponding N at amino acid position 752, which suggested that they could be
neuropathogenic EHV-1 strains. However, subsequent phylogenetic analysis of the
gG gene suggested that they were EHV-9 and not EHV-1.
PMID- 25852234
TI - Sleep duration and sleep quality following acute mild traumatic brain injury: a
propensity score analysis.
AB - INTRODUCTION: Mild traumatic brain injury (mTBI) has been widely studied and the
effects of injury can be long term or even lifelong. This research aims to
characterize the sleep problems of patients following acute mTBI. METHODS: A
total of 171 patients with mTBI within one month and 145 non-mTBI controls were
recruited in this study. The questionnaire, Pittsburgh Sleep Quality Index
(PSQI), was used to evaluate seven aspects of sleep problems. A propensity score
method was used to generate a quasirandomized design to account for the
background information, including gender, age, Beck's Anxiety Index, Beck's
Depression Index, and Epworth Sleepiness Scale. The effect was evaluated via
cumulative logit regression including propensity scores as a covariate. RESULTS:
Before adjustment, about 60% mTBI patients and over three quarters of control
subjects had mild sleep disturbance while one third mTBI patients had moderate
sleep disturbance. After adjusting by the propensity scores, the scores of sleep
quality and duration were significant between mTBI and control groups.
CONCLUSION: Our study supports that sleep problem is common in mTBI group. After
adjusting the confounders by propensity score, sleep duration and subjective
sleep quality are the most frequently reported problems in mTBI patients within
one month after the injury.
PMID- 25852235
TI - Corrigendum to "hypothermia reduces toll-like receptor 3-activated microglial
interferon-beta and nitric oxide production".
PMID- 25852236
TI - Editorial comment: preventing sudden death with implantable defibrillators in
octogenarians: too much too late?
PMID- 25852238
TI - Editorial Comment: Over, Under, or Just Right? How do we interpret ICD
utilization in the modern era?
PMID- 25852237
TI - Implantable cardioverter defibrillators in octogenarians: clinical outcomes from
a single center.
AB - AIMS: Limited data exist on outcomes in very elderly ICD recipients. We describe
outcomes in new ICD and Cardiac Resynchronisation Therapy with Defibrillator (CRT
D) implants in octogenarians at our institution. METHODS: Patients aged 80 years
and above who underwent de novo ICD or CRT-D implantation from January 2006 to
July 2012 were identified. Clinical data were collected from the procedural
record, medical and ICD notes. Baseline characteristics were compared using
independent sample t test for continuous variables and Fisher's exact test for
categorical variables. Kaplan-Meier curves were constructed. RESULTS: Ten per
cent of all new ICD/CRT-D implants were aged 80 years and over. Median age was
83.0 years. Median follow-up was 29 months. Death occurred in 17 (34%). Median
time to death was 23 months. Three deaths (6%) occurred within 12 months of ICD
implantation. Appropriate therapy (ATP or shock) occurred in 19 (38%).
Inappropriate therapy occurred in 6 (12%). Rates of appropriate shocks and
inappropriate therapy (shocks and ATP) and significant valvular incompetence were
higher amongst deceased patients (P=0.03 OR 5.9 95% CI 1.3-27) and (P=0.02 OR 12
95% CI 1.3-112). Univariate analysis identified diuretic use (P=0.008 95% C.I.
0.05 to 0.63) and appropriate shock (P= 0.025 95% C.I. 1.25 to 26.3) as
predictors of mortality. CONCLUSION: Octogenarians make up a small but increasing
number of ICD recipients. This study highlights high survival rates at one year
with acceptable rates of appropriate and inappropriate device therapy. Ongoing
debate regarding the appropriateness of ICD in very elderly patients is
warranted.
PMID- 25852240
TI - Editorial comment: syncope with heart disease - provoke and see or wait and watch
?
PMID- 25852239
TI - Under-Utilization of Implantable Cardioverter Defibrillators in Patients with
Heart Failure - The Current State of Sudden Cardiac Death Prophylaxis.
AB - BACKGROUND: Despite ACC/AHA guidelines indicating implantable cardioverter
defibrillator (ICD) as class I therapy for primary prevention of sudden cardiac
death in patients with EF<=35%, ICD utilization rates in real world practice have
been low. OBJECTIVE: To determine the rate of ICD implantation at a tertiary care
academic center and to assess the reasons for under-utilization of the same.
METHODS: Review of a prospectively collected database which included all patients
diagnosed with an EF<=35% was performed to assess the rate of ICD implantation
and mortality. Reasons for non-implantation of ICD were then assessed from
detailed chart review. RESULTS: A total of 707 patients (age 69.4 +/- 14.1 years)
with mean EF of 26+/-7% were analyzed. Only 28% (200/707) of patients had ICDs
implanted. Mortality was lower in the group with ICD (25% vs 37%, p=0.004). When
patients who either died or were lost to follow-up prior to 2005 were excluded,
ICD utilization rate was still low at 37.6%. The most common reason for non
implantation of ICD was physicians not discussing this option with their
patients. Patient refusal was the second most common reason. CONCLUSIONS: ICD
Implantation rates for primary prevention of SCD in patients with EF<=35% is low.
Physician and patient education should be addressed to improve the utilization
rates.
PMID- 25852241
TI - What is The Utility of Electrophysiological Study in Elderly Patients with
Syncope and Heart Disease?
AB - BACKGROUND: Syncope in elderly patients with heart disease is a growing problem.
Its aetiological diagnosis is often difficult. We intended to investigate the
value of the electrophysiological study (EPS) in old patients with syncope and
heart disease. METHODS: EPS was performed in 182 consecutive patients with
syncope and heart disease, among whom 62 patients were >=75 years old and 120
patients <75. RESULTS: Left ventricular ejection fraction was 43.9+/-11.7% in
patients >=75 and 41.1+/-12.6% in patients <75. During EPS, induced sustained
ventricular arrhythmias were as frequent in both groups (27.4% in patients >=75
versus 27.5% in patients <75, p=0.99) whereas AV conduction abnormalities were
more frequent in older patients (37.1% in patients >=75 versus 18.3% in patients
<75, p<0.005). Syncope remained unexplained in 35.5% of patients >=75 and in
51.7% of patients <75 (p>0.04). ICD was more likely to be implanted in younger
patients than in patients >=75 years (37.5% vs 21% respectively, p<0.009). During
a mean follow-up period of 3.3+/-3 years, the 4-year-survival rate was 66.9+/-6.8
% in patients >=75 and 75.9+/-6.2 % in patients <75 years. The main cause of
death was heart failure in both groups. The factors related to a worse outcome in
a multivariate analysis were low LVEF and higher age. CONCLUSION: Complete EPS
allows the identification of treatable causes in a high proportion of elderly
patients with syncope and heart disease. Yet, the prognosis of these patients is
mainly related to LVEF and age.
PMID- 25852242
TI - Channelopathies - emerging trends in the management of inherited arrhythmias.
AB - In spite of their relative rarity, inheritable arrhythmias have come to the
forefront as a group of potentially fatal but preventable cause of sudden cardiac
death in children and (young) adults. Comprehensive management of inherited
arrhythmias includes diagnosing and treating the proband and identifying and
protecting affected family members. This has been made possible by the vast
advances in the field of molecular biology enabling better understanding of the
genetic underpinnings of some of these disease groups, namely congenital long QT
syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada
syndrome. The ensuing knowledge of the genotype-phenotype correlations enables us
to risk-stratify, prognosticate and treat based on the genetic test results. The
various diagnostic modalities currently available to us, including clinical tools
and genetic technologies, have to be applied judiciously in order to promptly
identify those affected and to spare the emotional burden of a potentially lethal
disease in the unaffected individuals. The therapeutic armamentarium of inherited
arrhythmias includes pharmacological agents, device therapies and surgical
interventions. A treatment strategy keeping in mind the risk profile of the
patients, the local availability of drugs and the expertise of the treating
personnel is proving effective. While opportunities for research are numerous in
this expanding field of medicine, there is also tremendous scope for
incorporating the emerging trends in managing patients and families with
inherited arrhythmias in the Indian subcontinent.
PMID- 25852243
TI - Antegrade and retrograde decremental conduction properties of an accessory
pathway associated with the coronary sinus musculature.
AB - A 32-year-old man underwent catheter ablation of an orthodromic atrioventricular
reentrant tachycardia. The sinus rhythm electrocardiogram exhibited a normal PQ
interval and no delta waves, but atrial pacing produced a prolonged PQ interval
and wide QRS morphology with right bundle-branch block due to antegrade accessory
pathway (AP) conduction. During the tachycardia, atrial double potentials
consisting of the coronary sinus musculature (CSM) and left atrial (LA)
potentials were observed. Ventricular extrastimulation exhibited retrograde
decremental conduction with an identical atrial activation sequence as during the
tachycardia. A radiofrequency application within the posterolateral CS during
ventricular pacing eliminated the CSM-LA conduction and concomitantly the
ventriculoatrial conduction via the AP was abolished. In this case, the CSM was
associated with the bidirectional decremental conduction properties of the AP,
and the antegrade slow conduction resulted in the absence of a shortening of the
PQ interval and delta waves during sinus rhythm despite the continuous presence
of antegrade AP conduction.
PMID- 25852244
TI - Successful Implant of a Subcutaneous ICD System in a Patient with an Ipsilateral
Epicardial Pacemaker.
PMID- 25852245
TI - Novel use of the midas rex neurosurgical drill to release silicone glue entrapped
pacing leads.
PMID- 25852247
TI - Jumping across the gap - a series of atrial extrastimuli.
AB - The "gap phenomenon" is an interesting phenomenon in electrophysiology arising
from the differences in refractory periods at two or more levels of the
atrioventricular (AV) conduction system. We present a patient with dual AV nodal
physiology in whom the AH jump mediates the gap phenomenon. We also briefly
discuss the other mechanisms of gap phenomenon that have been described in this
setting.
PMID- 25852246
TI - Partial unroofed coronary sinus associated with upper septal ventricular
tachycardia and atrioventricular nodal reentrant tachycardia.
AB - A 58 year old gentleman with complaints of palpitations and documented
tachycardia was found to have a dilated right atrium, right ventricle and
coronary sinus, which were due to partial unroofed coronary sinus without a left
superior vena cava. He had upper septal ventricular tachycardia and atrio
ventricular nodal reentrant tachycardia, which was successfully treated by
radiofrequency ablation.
PMID- 25852248
TI - Peeling off the Mask: Pseudo Myocardial Infarction Pattern on Electrocardiogram
During AICD Implantation.
AB - Lead induced transient right bundle branch block is not uncommon during pacemaker
implantation. We describe a patient with old anterior wall myocardial infarction
with severe left ventricular dysfunction presenting with recurrent ventricular
tachycardia who developed transient right bundle branch block and
pseudomyocardial infacrction pattern during AICD implantation.
PMID- 25852249
TI - First Case of Automatic His Potential Detection With a Novel Ultra High-density
Electroanatomical Mapping System for AV Nodal Ablation.
AB - A 74-year old was considered for atrioventricular (AV) nodal ablation in view of
atrial fibrillation (AF) with poorly controlled ventricular rate despite being on
amiodarone. Targeted AV nodal ablation was successfully performed after
identifying the target site for ablation by reviewing an ultra high-density map
of the His region produced by automatic electrogram annotation.
PMID- 25852250
TI - Ventricular arrhythmias in arrhythmogenic right ventricular dysplasia.
PMID- 25852251
TI - Using aripiprazole to reduce antipsychotic-induced hyperprolactinemia: meta
analysis of currently available randomized controlled trials.
AB - BACKGROUND: Hyperprolactinemia (HPL) is a common side effect of antipsychotic
medications. Recent reports suggest that aripiprazole can ameliorate
antipsychotic-induced HPL, but results are inconsistent and the single available
systematic review only considered five studies. AIM: Conduct an updated meta
analysis of all randomized controlled trials (RCTs) about the efficacy and safety
of aripiprazole as an adjunctive treatment for antipsychotic-induced
hyperprolactinemia. METHODS: English and Chinese databases were searched for RCTs
about the use of aripiprazole in treating antipsychotic-induced HPL published by
January 20, 2015. Studies were selected using pre-defined inclusion and exclusion
criteria. The Cochrane Risk of Bias tool was used to evaluate risk of biases, the
Cochrane GRADE measure was used to assess the quality of evidence, and Review
Manager 5.3 software was used for data analysis. RESULTS: A total of 21 studies,
19 of which were conducted in mainland China, were included in the analysis. Meta
analysis of data from 8 of the studies with a pooled sample of 604 individuals
found that compared to the control condition adjunctive aripiprazole
significantly increased the proportion of participants who experienced HPL
recovery (risk ratio [RR]=19.2, 95%CI=11.0-33.5). The proportion who experienced
any adverse effect during follow-up did not differ between the two groups, but
the aripiprazole group was more likely to report somnolence (RR=2.76, 95%CI=1.34
5.69) and headaches (RR=2.31, 95%CI=1.08-4.92). High-dose aripiprazole (>5mg/day)
was more effective than low-dose (<5mg/day) aripiprazole (RR=30.0, 95%CI=10.2
120.7 v. RR=15.1, 95%CI=8.1-28.1), but this difference was not statistically
significant. The risk of bias in the studies was rated as 'high' in 6 of the
studies and 'unclear' in 15 studies, and the quality of evidence was rated as
'high' for only 7 of the 57 outcome measures assessed. CONCLUSIONS: This study
systematically reviewed and evaluated all relevant RCTs and found that adjunctive
aripiprazole is effective and safe to use in the treatment of antipsychotic
induced HPL. However, the low quality of some of the studies, the incomplete
methodological information provided for most of the studies, and the relatively
short follow-up time of the studies raises question about the validity of the
results. Further work that resolves these methodological and reporting issues is
needed.
PMID- 25852252
TI - Cross-sectional evaluation of the adequacy of guardianship by family members of
community-residing persons with mental disorders in Changning District, Shanghai.
AB - BACKGROUND: The disease burden associated with chronic psychiatric illnesses is
high and is projected to grow rapidly. A community-based management system for
persons with mental illness was established in Shanghai in 2012 based on the
Shanghai Mental Health Regulations that were developed to conform with China's
new mental health law. AIM: Evaluate the guardianship services provided by family
members to persons with mental illnesses living in the Changning District of
Shanghai. METHODS: The legal guardians of 4034 of the 4283 community-dwelling
persons with psychiatric disorders living in Changning District who are
registered in the Shanghai Information Management System of Mental Health were
interviewed by local community health doctors and local neighborhood committee
officials. The adequacy of guardianship was assessed based on standardized
criteria (including the guardian's regular attendance at mental health training
sessions, and their level of assistance in the treatment, daily life, and
rehabilitation of the patient) and the main reasons for inadequate guardianship
were recorded. RESULTS: The majority of guardians (3331, 83.6%) adequately
fulfilled their guardianship duties. Advanced age and ill-health of the guardian
was the main contributing factor in 87% of the 703 cases in which the
guardianship was classified as inadequate. Other factors associated with
inadequate guardianship included the patient's unstable clinical condition or
failure to adhere to medication, and when the guardian did not live in the same
household as the patient. The patient's diagnosis, the guardian's level of
education, and the relationship between the guardian and patient were also
associated with the adequacy of guardianship. CONCLUSIONS: The guardianship-based
community services for mentally ill individuals in urban China works reasonably
well. But the rapid aging of China's population may gradually decrease the
ability of China's families to continue to assume this heavy burden. Alternative
models of providing high-quality, community-based services for persons with
mental disorders need to be developed as part of the roll-out of China's new
mental health law.
PMID- 25852253
TI - Social media and suicide prevention: findings from a stakeholder survey.
AB - BACKGROUND: Suicide is a leading cause of death, particularly among young adults.
The rapid growth of social media and its heavy use by young adults presents new
challenges and opportunities for suicide prevention. Social media sites are
commonly used for communicating about suicide-related behavior with others, which
raises the possibility of using social media to help prevent suicide. However,
the use of social media varies widely between different suicide prevention
advocates. The role this type of intervention should play in a community's
overall suicide prevention strategy remains a matter of debate. AIM: Explore the
ways in which stakeholders use social media for suicide prevention and assess
their views about the potential utility of social media as a suicide prevention
tool. METHODS: A 12-week stakeholder consultation that involved the online
administration and completion of surveys by 10 individuals who conduct research
about suicide and social media, 13 organizations that use social media for
suicide prevention purposes, and 64 users of social media. RESULTS: Social media
was seen as a useful means of delivering a range of suicide prevention
activities. Respondents reported that the key benefits of social media were the
opportunity to obtain emotional support from others, to express one's feelings,
to talk to others with similar problems, and to provide help to others. The
social media site believed to hold most potential for delivering suicide
prevention activities was Facebook. There were concerns about potential risks of
social media, but respondents felt the potential benefits outweighed the risks.
CONCLUSIONS: Social media was recognized by different types of stakeholders as
holding potential for delivering suicide prevention activities. More research is
required to establish the efficacy and safety of potential social media-based
interventions and ethical standards and protocols to ensure that such
interventions are delivered safely need to be developed and implemented.
PMID- 25852254
TI - Comparison of the personality and other psychological factors of students with
internet addiction who do and do not have associated social dysfunction.
AB - BACKGROUND: There is ongoing controversy about whether or not internet addiction
should be considered a non-substance behavioral addiction (like gambling
disorder) and, if so, what diagnostic criteria should be used to define the
condition. Current criteria for internet addiction give equal diagnostic weight
to the physiological symptoms and the social consequences of internet addiction.
AIM: Assess the psychological correlates of social dysfunction among individuals
with internet addiction. METHODS: A total of 133 students who sought treatment at
the Guangji Psychiatric Hospital from July 2011 to December 2013 for
psychological problems related to excessive internet use and who currently met
Young criteria for internet addiction were identified; 31 of the 38 students who
meet rigorous criteria for concurrent internet-related social dysfunction and a
random sample of 44 of the 95 students without concurrent social dysfunction
completed a battery of psychosocial measures: seven supplementary scales of the
Minnesota Multiphasic Personality Inventory (MMPI), the Egna Minnen av Barndoms
Uppfostran perceived parenting scale, the Perceived Social Support Scale, the
Trait Coping Style Questionnaire, and the Symptom Checklist 90. RESULTS: Compared
to persons with internet addiction without accompanying social dysfunction, those
with social dysfunction had higher levels of interpersonal sensitivity,
hostility, and paranoia; lower levels of social responsibility, anxiety, self
control, and family social support; and they were more likely to employ negative
coping strategies. There were however, no differences in perceived parenting
styles between the two groups. CONCLUSIONS: A relatively small proportion of
individuals who meet the physiological markers of internet addiction
simultaneously report significant internet-related social dysfunction. There are
several psychosocial measures that distinguish persons with internet addiction
who do or do not have concurrent social dysfunction. Further research is needed
to determine whether or not these are two distinct subtypes of internet addiction
and whether or not persons with internet addiction without concurrent social
dysfunction should be classified as suffering from a 'mental disorder'.
PMID- 25852255
TI - Psychosis risk syndrome is not prodromal psychosis.
AB - One of the most exciting trends in schizophrenia research is the shift in focus
from treatment studies to studies about the early identification and prevention
of schizophrenia. These studies have primarily focused on adolescents or young
adults with prodromal symptoms or on clinically high-risk individuals who show
similar impairments in cognitive and social functioning to those seen in
individuals with schizophrenia and, thus, are considered at high risk of
developing schizophrenia or other psychotic disorders. Some researchers have
labeled this condition as psychosis risk syndrome (PRS). There are moves in some
circles to re-define the condition as a disorder in its own right: the American
Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders
5(th) edition (DSM-5), lists 'attenuated psychosis syndrome' (APS) in the
appendix as a condition for further study. Individuals with PRS are certainly at
higher risk of developing a psychotic disorder than those without PRS, but the
majority of those with PRS do not subsequently develop a psychotic disorder, so
we argue against the inclusion of PRS or APS as a subtype of schizophrenia
spectrum disorder.
PMID- 25852256
TI - Challenges in the early detection and intervention of the psychosis-risk
syndrome.
AB - The concept of a clinical high-risk state for psychosis has been used to describe
individuals who have prodromal symptoms of psychosis and, thus, are at high-risk
of developing psychosis. This high-risk concept promotes a more detailed
developmental understanding of the evolution of psychosis and provides a
theoretical basis for providing necessary mental health services to people at
clinically high-risk of developing psychosis. Early detection and intervention
can potentially change the course of psychotic conditions and, thus, prevent or
minimize the associated disability. This is a relatively new area of interest, so
more studies are needed to fully understand this high-risk condition.
PMID- 25852257
TI - Attenuated psychosis syndrome: benefits of explicit recognition.
AB - Given the unique characteristics of people who meet criteria for attenuated
psychosis syndrome (APS) and the growing literature on the clinical benefits of
providing services to individuals who meet these criteria, the APS diagnosis
serves an important, and previously missing, role in psychiatry. The promotion of
the APS diagnosis should help reduce the over-diagnosis and over-treatment of
individuals with prodromal psychotic conditions and it should also encourage
expanded training about attenuated psychosis among clinicians who primarily
provide services to youth (a primary group who are diagnosed with APS). Only some
of the individuals with APS subsequently develop psychosis, but all have existing
clinical needs - regardless of subsequent conversion. The formal recognition of
APS in DSM-5 will facilitate the research needed to identify and meet those
needs.
PMID- 25852258
TI - Case report of rabies-induced persistent mental symptoms.
AB - Rabies is a viral infection with a high case fatality rate. Typical symptoms of
rabies include hydrophobia, pharynx muscle spasms, and progressive paralysis.
Rabies-induced persistent mental disturbances are rare. Here we report a 22-year
old male who was infected with rabies after being attacked by a dog. He did not
receive rabies vaccine immediately after the incident and was only provided with
non-standard treatment at a local clinic. A week later he became disorientated,
paranoid, and aggressive. One month after the attack, rabies antibody was found
in his cerebrospinal fluid and a Magnetic Resonance Imaging (MRI) examination of
his head revealed abnormal signals in the putamina, caudate nucleus, and insula.
His mental symptoms persisted for six years and his daily functioning was
severely impaired, but his vital signs were stable without signs of brain stem
damage. Six years after the incident, a repeat MRI showed brain atrophy.
PMID- 25852259
TI - Brief Chinese version of the Family Experience Interview Schedule to assess
caregiver burden of family members of individuals with mental disorders.
AB - BACKGROUND: Caregiver burden is an important issue that needs to be addressed
when developing management programs for persons with chronic mental illnesses,
but there is, as yet, no reliable way for assessing this in China. AIM: Assess
the validity and reliability of a brief adapted Chinese version of the Family
Experience Interview Schedule (FEIS) among caregivers of inpatients with mental
disorders in China. METHODS: We first translated and back-translated the original
114-item FEIS and administered it to 606 primary caregivers of psychiatric
inpatients. After excluding 9 items about sociodemographic variables and 9 items
that over 15% of respondents were unable to answer, we conducted an exploratory
factor analysis using a random half of the sample on the remaining 96 items and,
based on the results of the factor analysis, selected the items to be included in
the final shortened scale. Correlation analysis, confirmatory factor analysis,
and internal consistency measures were used to assess the reliability and
validity of the final scale using data from the second half of the sample.
RESULTS: The final scale included 28 items that loaded on five dimensions: (a)
patients' violent behavior; (b) patients' suicidal tendency; (c) caregivers'
depression and anxiety; (d) disruption of caregivers' daily routines; and (e)
caregivers' satisfaction with health services. These five dimensions explained
50.5% of the total variance. Confirmatory factor analysis found reasonable fit of
this 5-factor model (chi (2) /df=2.94, p<0.001, goodness-of-fit index [GFI]=0.85,
comparative fit index [CFI]=0.85, root-mean-square error of approximation
[RMSEA]=0.08). The correlation coefficients between each item and the
corresponding factor were all above 0.5. The Cronbach alpha coefficient of the
entire scale was 0.76 and that for the five dimensions varied between 0.71 and
0.84. CONCLUSION: The five dimensions of family burden assessed by the 28-item
brief Chinese version of FEIS have good internal consistency and, thus, appear to
assess valid dimensions of family burden in Chinese caregivers of persons with
serious mental illnesses. Further work is needed to assess the test-retest
reliability of this scale and its sensitivity to change over time.
PMID- 25852260
TI - Kappa coefficient: a popular measure of rater agreement.
AB - In mental health and psychosocial studies it is often necessary to report on the
between-rater agreement of measures used in the study. This paper discusses the
concept of agreement, highlighting its fundamental difference from correlation.
Several examples demonstrate how to compute the kappa coefficient - a popular
statistic for measuring agreement - both by hand and by using statistical
software packages such as SAS and SPSS. Real study data are used to illustrate
how to use and interpret this coefficient in clinical research and practice. The
article concludes with a discussion of the limitations of the coefficient.
PMID- 25852261
TI - Field cancerisation in colorectal cancer: a new frontier or pastures past?
AB - Despite considerable advances in our understanding of cancer biology, early
diagnosis of colorectal cancer remains elusive. Based on the adenoma-carcinoma
sequence, cancer develops through the progressive accumulation of mutations in
key genes that regulate cell growth. However, recent mathematical modelling
suggests that some of these genetic events occur prior to the development of any
discernible histological abnormality. Cells acquire pro-tumourigenic mutations
that are not able to produce morphological change but predispose to cancer
formation. These cells can grow to form large patches of mucosa from which a
cancer arises. This process has been termed "field cancerisation". It has
received little attention in the scientific literature until recently. Several
studies have now demonstrated cellular, genetic and epigenetic alterations in the
macroscopically normal mucosa of colorectal cancer patients. In some reports,
these changes were effectively utilised to identify patients with a neoplastic
lesion suggesting potential application in the clinical setting. In this article,
we present the scientific evidence to support field cancerisation in colorectal
cancer and discuss important limitations that require further investigation.
Characterisation of the field defect is necessary to enable early diagnosis of
colorectal cancer and identify molecular targets for chemoprevention. Field
cancerisation offers a promising prospect for experimental cancer research and
has potential to improve patient outcomes in the clinical setting.
PMID- 25852262
TI - Helicobacter pylori eradication in gastric diffuse large B cell lymphoma.
AB - Diffuse large B cell lymphoma (DLBCL) of the stomach is a heterogenous disease.
There are tumors without histological evidence of mucosa-associated lymphoid
tissue (MALT) lymphoma, which are classified as pure or de novo DLBCL and those
with evidence of MALT, which are classified as DLBCL (MALT). The association
between Helicobacter pylori (H. pylori) and gastric MALT lymphoma and remission
with H. pylori eradication was shown in the 1990s. In recent years, scientists
from Taiwan and others have shown that high-grade gastric lymphomas may be
dependent on H. pylori and eradication of this microorganism is effective in
these cases. This entity is biologically distinct from H. pylori (-) cases and
has a better clinical outcome. There are sufficient data about the complete
remission in some of these cases with brief treatment with antibiotics. With this
strategy, it is possible to save some of these cases from the harmful effects of
standard chemotherapy. It is time to treat these cases with H. pylori
eradication. However, strict histopathological follow-up is crucial and
histopathological response must be evaluated according to the scoring system
proposed by Groupe d'Etude des Lymphomes de l'Adulte. If there is no sufficient
response, chemotherapy must be given immediately. These results suggest that H.
pylori dependency and high-grade transformation in gastric MALT lymphomas are
distinct events.
PMID- 25852263
TI - Current pharmacological therapies for nonalcoholic fatty liver
disease/nonalcoholic steatohepatitis.
AB - Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is
considered to be a hepatic manifestation of metabolic syndrome, and its incidence
is rapidly increasing worldwide. It is currently the most common chronic liver
disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and
may result in liver-related death. Currently, the principal treatment for
NAFLD/NASH is lifestyle modification by diet and exercise. However,
pharmacological therapy is indispensable because obese patients with NAFLD often
have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH
has not been completely elucidated. However, insulin resistance, inflammatory
cytokines, and oxidative stress are thought to be important in the development
and/or progression of the disease. Currently, insulin sensitizers
(thiazolidinediones) and antioxidants (vitamin E) seem to be the most promising
therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline,
angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have
promise. However, there is a lack of consensus regarding the most effective and
appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that
herbal medicines and natural products may be promising therapeutic agents for
NAFLD/NASH, but their efficacy and safety are yet to be investigated in human
studies. In this paper, we review the existing and potential pharmacological
therapies for NAFLD/NASH.
PMID- 25852265
TI - Gastrointestinal Behcet's disease: a review.
AB - Behcet's disease (BD) is an idiopathic, chronic, relapsing, multi-systemic
vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular
disease and skin lesions. Prevalence of BD is highest in countries along the
ancient silk road from the Mediterranean basin to East Asia. By comparison, the
prevalence in North American and Northern European countries is low.
Gastrointestinal manifestations of Behcet's disease are of particular importance
as they are associated with significant morbidity and mortality. Although
ileocecal involvement is most commonly described, BD may involve any segment of
the intestinal tract as well as the various organs within the gastrointestinal
system. Diagnosis is based on clinical criteria - there are no pathognomonic
laboratory tests. Methods for monitoring disease activity on therapy are
available but imperfect. Evidence-based treatment strategies are lacking.
Different classes of medications have been successfully used for the treatment of
intestinal BD which include 5-aminosalicylic acid, corticosteroids,
immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody
therapy. Like inflammatory bowel disease, surgery is reserved for those who are
resistant to medical therapy. A subset of patients have a poor disease course.
Accurate methods to detect these patients and the optimal strategy for their
treatment are not known at this time.
PMID- 25852264
TI - Hepatitis C virus and antiviral innate immunity: who wins at tug-of-war?
AB - Hepatitis C virus (HCV) is a major human pathogen of chronic hepatitis and
related liver diseases. Innate immunity is the first line of defense against
invading foreign pathogens, and its activation is dependent on the recognition of
these pathogens by several key sensors. The interferon (IFN) system plays an
essential role in the restriction of HCV infection via the induction of hundreds
of IFN-stimulated genes (ISGs) that inhibit viral replication and spread.
However, numerous factors that trigger immune dysregulation, including viral
factors and host genetic factors, can help HCV to escape host immune response,
facilitating viral persistence. In this review, we aim to summarize recent
advances in understanding the innate immune response to HCV infection and the
mechanisms of ISGs to suppress viral survival, as well as the immune evasion
strategies for chronic HCV infection.
PMID- 25852266
TI - New gene therapy strategies for hepatic fibrosis.
AB - The liver is the largest internal organ of the body, which may suffer acute or
chronic injury induced by many factors, leading to cirrhosis and hepatocarcinoma.
Cirrhosis is the irreversible end result of fibrous scarring and hepatocellular
regeneration, characterized by diffuse disorganization of the normal hepatic
structure, regenerative nodules and fibrotic tissue. Cirrhosis is associated with
a high co-morbidity and mortality without effective treatment, and much research
has been aimed at developing new therapeutic strategies to guarantee recovery.
Liver-based gene therapy has been used to downregulate specific genes, to block
the expression of deleterious genes, to delivery therapeutic genes, to prevent
allograft rejection and to augment liver regeneration. Viral and non-viral
vectors have been used, with viral vectors proving to be more efficient. This
review provides an overview of the main strategies used in liver-gene therapy
represented by non-viral vectors, viral vectors, novel administration methods
like hydrodynamic injection, hybrids of two viral vectors and blocking molecules,
with the hope of translating findings from the laboratory to the patient's bed
side.
PMID- 25852268
TI - Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide.
Surgery, percutaneous ablation and liver transplantation are the only curative
treatment modalities for HCC. However, the majority of patients have unresectable
disease at diagnosis. Therefore, effective treatment options for patients with
advanced HCC are required. In advanced HCC, according to current international
guidelines, sorafenib, a molecular targeted agent, is the standard treatment.
However, alternative treatment modalities are required because of the low
response rates and unsuitability of molecular agents in real practice. In various
treatment modalities, mostly in Asia, hepatic arterial infusion chemotherapy
(HAIC) has been applied to advanced HCC with a view to increasing the therapeutic
efficacy. HAIC provides direct drug delivery into the tumor feeding vessels and
also minimizes systemic toxicities through a greater first-pass effect in the
liver. However, the sample sizes of studies on HAIC have been small and large
randomized trials are still lacking. In this article, we describe the treatment
efficacy of HAIC for advanced stage HCC and discuss future therapeutic
possibilities.
PMID- 25852267
TI - Current management of hepatocellular carcinoma: an Eastern perspective.
AB - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death,
especially in Eastern areas. With advancements in diagnosis and treatment
modalities for HCC, the survival and prognosis of HCC patients are improving.
However, treatment patterns are not uniform between areas despite efforts to
promote a common protocol. Although many hepatologists in Asian countries may
adopt the principles of the Barcelona Clinic Liver Cancer staging system, they
are also independently making an effort to expand the indications of each
treatment and to combine therapies for better outcomes. Several expanded criteria
for liver transplantation in HCC have been developed in Asian countries. Living
donor liver transplantation is much more commonly performed in these countries
than deceased donor liver transplantation, and it may be preceded by other
treatments such as the down-staging of tumors. Local ablation therapies are often
combined with transarterial chemoembolization (TACE) and the outcome is
comparable to that of surgical resection. The indications of TACE are expanding,
and there are new types of transarterial therapies. Although data on drug-eluting
beads, TACE, and radioembolization in Asian countries are still relatively sparse
compared with Western countries, these methods are gradually gaining popularity
because of better tolerability and the possibility of improved response rates.
Hepatic arterial infusion chemotherapy and radiotherapy are not included in
Western guidelines, but are currently being used actively in several Asian
countries. For more advanced HCCs, appropriate combinations of TACE,
radiotherapy, and sorafenib can be considered, and emerging data indicate
improved outcomes of combination therapies compared with single therapies. To
include these paradigm shifts into newer treatment guidelines, more studies may
be needed, but they are certainly in progress.
PMID- 25852269
TI - Adjuvant therapy for gastric cancer: what have we learned since INT0116?
AB - Gastric cancer is one of the main cancer-related causes of death worldwide. The
curative treatment of gastric cancer consists of tumor resection and
lymphadenectomy. However, surgical treatment alone is associated with high
recurrence rates. Adjuvant treatment strategies have been studied over the last
decades, but there have been controversial results from the initial studies. The
pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy
with 5-fluorouracil increases relapse-free and overall survival, and it has been
adopted across the Western world. The high toxicity of radiochemotherapy and
suboptimal surgical treatment employed, with fewer than 10% of the patients
submitted to D2 lymphadenectomy, were the main study limitations. Since its
publication, other adjuvant treatment modalities have been studied, and
radiochemotherapy is being refined to improve its efficacy and safety. A
multimodal approach has been demonstrated to significantly increase relapse-free
and overall survival, and it can be offered in the form of perioperative
chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of
the extent of lymphadenectomy. The objective of the present review is to report
the major advances obtained in the last decades in the adjuvant treatment of
gastric cancer as well as the perspectives of treatment based on recent knowledge
of the molecular biology of the disease.
PMID- 25852270
TI - Antiviral therapies for hepatitis B virus-related hepatocellular carcinoma.
AB - Chronic hepatitis B virus (HBV) infection is a critical risk factor for the
carcinogenesis and progression of hepatocellular carcinoma (HCC). It promotes HCC
development by inducing liver fibrogenesis, genetic and epigenetic alterations,
and the expression of active viral-coded proteins. Effective antiviral treatments
inhibit the replication of HBV, reduce serum viral load and accelerate hepatitis
B e antigen serum conversion. Timely initiation of antiviral treatment is not
only essential for preventing the incidence of HCC in chronic hepatitis B
patients, but also important for reducing HBV reactivation, improving liver
function, reducing or delaying HCC recurrence, and prolonging overall survival of
HBV-related HCC patients after curative and palliative therapies. The selection
of antiviral drugs, monitoring of indicators such as HBV DNA and hepatitis B
surface antigen, and timely rescue treatment when necessary, are essential in
antiviral therapies for HBV-related HCC.
PMID- 25852272
TI - Fucosylation is a common glycosylation type in pancreatic cancer stem cell-like
phenotypes.
AB - AIM: To evaluate/isolate cancer stem cells (CSCs) from tissue or cell lines
according to various definitions and cell surface markers. METHODS: Lectin
microarray analysis was conducted on CSC-like fractions of the human pancreatic
cancer cell line Panc1 by establishing anti-cancer drug-resistant cells. Changes
in glycan structure of CSC-like cells were also investigated in sphere-forming
cells as well as in CSC fractions obtained from overexpression of CD24 and CD44.
RESULTS: Several types of fucosylation were increased under these conditions, and
the expression of fucosylation regulatory genes such as fucosyltransferases, GDP
fucose synthetic enzymes, and GDP-fucose transporters were dramatically enhanced
in CSC-like cells. These changes were significant in gemcitabine-resistant cells
and sphere cells of a human pancreatic cancer cell line, Panc1. However,
downregulation of cellular fucosylation by knockdown of the GDP-fucose
transporter did not alter gemcitabine resistance, indicating that increased
cellular fucosylation is a result of CSC-like transformation. CONCLUSION:
Fucosylation might be a biomarker of CSC-like cells in pancreatic cancer.
PMID- 25852271
TI - Insulin-like growth factor-1 mRNA isoforms and insulin-like growth factor-1
receptor mRNA expression in chronic hepatitis C.
AB - AIM: To evaluate the expression of different insulin-like growth factor (IGF)-1
mRNA isoforms and IGF-1 receptor (IGF-1R) mRNA in hepatitis C virus (HCV)
infected livers. METHODS: Thirty-four liver biopsy specimens from chronic
hepatitis C (CH-C) patients were obtained before anti-viral therapy. Inflammatory
activity (grading) and advancement of fibrosis (staging) were evaluated using a
modified point scale of METAVIR. The samples were analyzed using quantitative
real-time PCR technique. From fragments of liver biopsies and control liver that
were divided and ground in liquid nitrogen, RNA was isolated using RNeasy Fibrous
Tissue Mini Kit according to the manufacturer's instruction. Expression levels of
IGF-1 mRNA isoforms (IGF-1A, IGF-1B, IGF-1C, P1, and P2) and IGF-1R mRNA were
determined through normalization of copy numbers in samples as related to
reference genes: glyceraldehyde-3-phosphate dehydrogenase and hydroxymethylbilane
synthase. Results on liver expression of the IGF-1 mRNA isoforms and IGF-1R
transcript were compared to histological alterations in liver biopsies and with
selected clinical data in the patients. Statistical analysis was performed using
Statistica PL v. 9 software. RESULTS: The study showed differences in
quantitative expression of IGF-1 mRNA variants in HCV-infected livers, as
compared to the control. Higher relative expression of total IGF-1 mRNA and of
IGF-1 mRNAs isoforms (P1, A, and C) in HCV-infected livers as compared to the
control were detected. Within both groups, expression of the IGF-1A mRNA isoform
significantly prevailed over expressions of B and C isoforms. Expression of P1
mRNA was higher than that of P2 only in CH-C. Very high positive correlations
were detected between reciprocal expressions of IGF-1 mRNA isoforms P1 and P2 (r
= 0.876). Expression of P1 and P2 mRNA correlated with IGF-1A mRNA (r = 0.891; r
= 0.821, respectively), with IGF-1B mRNA (r = 0.854; r = 0.813, respectively),
and with IGF-1C mRNA (r = 0.839; r = 0.741, respectively). Expression of IGF-1A
mRNA significantly correlated with isoform B and C mRNA (r = 0.956; r = 0.869,
respectively), and B with C isoforms (r = 0.868) (P < 0.05 in all cases). Lower
expression of IGF-1A and B transcripts was noted in the more advanced liver
grading (G2) as compared to G1. Multiple negative correlations were detected
between expression of various IGF-1 transcripts and clinical data (e.g., alpha
fetoprotein, HCV RNA, steatosis, grading, and staging). Expression of IGF-1R mRNA
manifested positive correlation with grading and HCV-RNA. CONCLUSION: Differences
in quantitative expression of IGF-1 mRNA isoforms in HCV-infected livers, as
compared to the control, suggest that HCV may induce alteration of IGF-1 splicing
profile.
PMID- 25852273
TI - Esophageal variceal pressure influence on the effect of ligation.
AB - AIM: To explore the effect of in vitro porcine esophageal variceal pressure on
complete ligation degree for polycyclic ligators. METHODS: An in vitro model of
experimental porcine venous vessels was used to test various venous pressures.
Three treatment groups were designated according to the preset pressure range: P1
= 25-30 cmH2O; P2 = 35-40 cmH2O; P3 = 45-50 cmH2O. The effect of pressure on
ligation was assessed and compared among the groups. RESULTS: Complete ligation
was achieved at a rate of 56.25% (18/32) in group P1, 37.5% (12/32) in group P2,
and 33.33% (11/33) in group P3 (chi (2) = 3.6126; P = 0.0573). CONCLUSION: Higher
variceal pressures impair the ligation completion rate. Therefore, measuring
variceal pressure may help predict the effect of endoscopic ligation and guide
treatment choice.
PMID- 25852274
TI - Caffeic acid phenethyl ester inhibits liver fibrosis in rats.
AB - AIM: To investigate the hepatoprotective effects and antioxidant activity of
caffeic acid phenethyl ester (CAPE) in rats with liver fibrosis. METHODS: A total
of 75 male Sprague-Dawley rats were randomly assigned to seven experimental
groups: a normal group (n = 10), a vehicle group (n = 10), a model group (n =
15), a vitamin E group (n = 10), and three CAPE groups (CAPE 3, 6 and 12 mg/kg, n
= 10, respectively). Liver fibrosis was induced in rats by injecting CCl4
subcutaneously, feeding with high fat forage, and administering 30% alcohol
orally for 10 wk. Concurrently, CAPE (3, 6 and 12 mg/kg) was intraperitoneally
administered daily for 10 wk. After that, serum total bilirubin (TBil),
aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured
to assess hepatotoxicity. To investigate antioxidant activity of CAPE,
malondialdehyde (MDA), glutathione (GSH) levels, catalase (CAT) and superoxide
dismutase (SOD) activities in liver tissue were determined. Moreover, the effect
of CAPE on alpha-smooth muscle actin (alpha-SMA), a characteristic hallmark of
activated hepatic stellate cells (HSCs), and NF-E2-related factor 2 (Nrf2), a key
transcription factor for antioxidant systems, was investigated by
immunohistochemistry. RESULTS: Compared to the model group, intraperitoneal
administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats
(P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In
addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE
groups were markedly lower than that in the model group (P < 0.05 and P < 0.001,
respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH
levels, as well as CAT and SOD activities in liver fibrosis rats compared to the
model group (P < 0.05). Moreover, CAPE effectively inhibited alpha-SMA expression
while increasing Nrf2 expression compared to the model group (P < 0.01).
CONCLUSION: The protective effects of CAPE against liver fibrosis may be due to
its ability to suppress the activation of HSCs by inhibiting oxidative stress.
PMID- 25852275
TI - Interferon-lambda3 polymorphisms in pegylated-interferon-alpha plus ribavirin
therapy for genotype-2 chronic hepatitis C.
AB - AIM: To evaluate interferon-lambda3 (IFNL3) polymorphisms in response-guided
pegylated interferon-alpha plus ribavirin (Peg-IFNalpha/RBV) therapy for genotype
2 (G2) chronic hepatitis C. METHODS: Between January 2006 and June 2012, a total
of 180 patients with chronic infections of G2 hepatitis C virus (HCV) were
treated with response-guided Peg-IFNalpha/RBV therapy. The treatment duration was
24 wk for patients who achieved rapid virologic response (RVR), and 36 or 48 wk
for patients who did not. Then, the impact of the IFNL3 single nucleotide
polymorphism genotype (TT/non-TT at rs8099917) on treatment outcomes was
evaluated in the 180 patients, and between patients infected with either HCV sub
genotype 2a or 2b. RESULTS: Of the 180 patients evaluated, 111 achieved RVR,
while the remaining 69 patients did not. In RVR patients, the sustained virologic
response (SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR
rate (96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR
patients, the SVR rate decreased to 72.5% (P < 0.0001), and this rate was
significantly different between the IFNL3 genotype TT and non-TT groups (80.0% vs
42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients
identified the IFNL3 genotype TT as the only baseline-significant factor
associated with SVR (OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis
according to HCV sub-genotype, no significant difference in the SVR rate was
found between HCV sub-genotypes 2a and 2b. CONCLUSION: In response-guided Peg
IFNalpha/RBV combination therapy for chronically HCV G2-infected patients, the
impact of the IFNL3 genotype on SVR was limited to non-RVR patients.
PMID- 25852276
TI - Hepatitis C virus recurrence after liver transplantation: a 10-year evaluation.
AB - AIM: To evaluate the predictors of 10-year survival of patients with hepatitis C
recurrence. METHODS: Data from 358 patients transplanted between 1989 and 2010 in
two Italian transplant centers and with evidence of hepatitis C recurrence were
analyzed. A chi(2), Fisher's exact test and Kruskal Wallis' test were used for
categorical and continuous variables, respectively. Survival analysis was
performed at 10 years after transplant using the Kaplan-Meier method, and a log
rank test was used to compare groups. A P level less than 0.05 was considered
significant for all tests. Multivariate analysis of the predictive role of
different variables on 10-year survival was performed by a stepwise Cox logistic
regression. RESULTS: The ten-year survival of the entire population was 61.2%.
Five groups of patients were identified according to the virological response or
lack of a response to antiviral treatment and, among those who were not treated,
according to the clinical status (mild hepatitis C recurrence, "too sick to be
treated" and patients with comorbidities contraindicating the treatment). While
the 10-year survival of treated and untreated patients was not different (59.1%
vs 64.7%, P = 0.192), patients with a sustained virological response had a higher
10-year survival rate than both the "non-responders" (84.7% vs 39.8%, P < 0.0001)
and too sick to be treated (84.7% vs 0%, P < 0.0001). Sustained virological
responders had a survival rate comparable to patients untreated with mild
recurrence (84.7% vs 89.3%). A sustained virological response and young donor age
were independent predictors of 10-year survival. CONCLUSION: Sustained
virological response significantly increased long-term survival. Awaiting the
interferon-free regimen global availability, antiviral treatment might be
questionable in selected subjects with mild hepatitis C recurrence.
PMID- 25852277
TI - Clinical and computed tomography findings of appendiceal diverticulitis vs acute
appendicitis.
AB - AIM: To study the clinical features and computed tomography (CT) findings of
appendiceal diverticulitis vs acute appendicitis. METHODS: We retrospectively
reviewed the records of 451 patients who had undergone appendectomy in our
institution from January 2007 to September 2012. Patient demographics, clinical
features, pathological findings, and surgical outcomes were analyzed. We also
compared preoperative CT images of 25 patients with appendiceal diverticulitis
with those of 25 patients with acute appendicitis. RESULTS: Among 451 patients,
44 (9.7%) were diagnosed to have appendiceal diverticulitis and 398 (86.9%) to
have acute appendicitis. Patients with appendiceal diverticulitis were older (59
vs 37 years, P < 0.001) and had a longer duration of the illness (4.0 d vs 1.0 d,
P < 0.001). Perforation rates in patients with appendiceal diverticulitis were
higher (68% vs 27%, P < 0.001). The appendix could be visualized in only 13
patients (52%) among the appendiceal diverticulitis cases, but in all acute
appendicitis cases. CT findings suggestive of appendiceal diverticulitis included
the absence of fluid collection in the appendix (84% vs 12%, P < 0.001), absence
of appendicolith (92% vs 52%, P = 0.005), and formation of abscess (68% vs 16%, P
< 0.001). Appendiceal diverticula were identified in 6 patients (24%).
CONCLUSION: Among patients who had undergone appendectomy, 9.7% had appendiceal
diverticulitis. Patients with appendiceal diverticulitis had different clinical
features and CT findings from patients with acute appendicitis.
PMID- 25852278
TI - Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus
associated hepatocellular carcinoma.
AB - AIM: To determine the cutoff values and to compare the diagnostic role of alpha
fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in
chronic hepatitis B (CHB). METHODS: A total of 1255 patients with CHB, including
157 patients with hepatocellular carcinoma (HCC), 879 with non-cirrhotic CHB and
219 with cirrhosis without HCC, were retrospectively enrolled. The areas under
the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP and their
combination were calculated and compared. RESULTS: The optimal cutoff values for
PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the
differentiation of HCC from nonmalignant CHB. The sensitivity and specificity
were 73.9% and 89.7%, respectively, for PIVKA-II and 67.5% and 90.3% for AFP,
respectively. The AUROC curves of both PIVKA-II and AFP were not significantly
different (0.854 vs 0.853, P = 0.965) for the differentiation of HCC from
nonmalignant CHB, whereas the AUROC of PIVKA-II was significantly better than
that of AFP in patients with cirrhosis (0.870 vs 0.812, P = 0.042). When PIVKA-II
and AFP were combined, the diagnostic power improved significantly compared to
either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB
(P < 0.05), especially when cirrhosis was present (P < 0.05). CONCLUSION: Serum
PIVKA-II might be a better tumor marker than AFP, and its combination with AFP
may enhance the early detection of HCC in patients with CHB.
PMID- 25852279
TI - Eradication rate and histological changes after Helicobacter pylori eradication
treatment in gastric cancer patients following subtotal gastrectomy.
AB - AIM: To investigate the eradication rate and histological changes after
Helicobacter pylori (H. pylori) eradication treatment following subtotal
gastrectomy for gastric cancer. METHODS: A total of 610 patients with H. pylori
infection who had undergone surgery for either early or advanced gastric
adenocarcinoma between May 2004 and December 2010 were retrospectively studied. A
total of 584 patients with proven H. pylori infection after surgery for gastric
cancer were enrolled in this study. Patients received a seven day standard triple
regimen as first-line therapy and a 10 d bismuth-containing quadruple regimen as
second-line therapy in cases of eradication failure. The patients underwent an
esophagogastroduodenoscopy (EGD) between six and 12 mo after surgery, followed by
annual EGDs. A further EGD was conducted 12 mo after confirming the result of the
eradication and the histological changes. A gastric biopsy specimen for
histological examination and Campylobacter-like organism testing was obtained
from the lesser and greater curvature of the corpus of the remnant stomach.
Histological changes in the gastric mucosa were assessed using the updated Sydney
system before eradication therapy and at follow-up after 12 mo. RESULTS:
Eradication rates with the first-line and second-line therapies were 78.4%
(458/584) and 90% (36/40), respectively, by intention-to-treat analysis and 85.3%
(458/530) and 92.3% (36/39), respectively, by per-protocol analysis. The
univariate and multivariate analyses revealed that Billroth II surgery was an
independent factor predictive of eradication success in the eradication success
group (OR = 1.53, 95%CI: 1.41-1.65, P = 0.021). The atrophy and intestinal
metaplasia (IM) scores 12 mo after eradication were significantly lower in the
eradication success group than in the eradication failure group (0.25 +/- 0.04 vs
0.47 +/- 0.12, P = 0.023; 0.27 +/- 0.04 vs 0.51 +/- 0.12, P = 0.015,
respectively). The atrophy and IM scores 12 mo after successful eradication were
significantly lower in the Billroth II group than in the Billroth I group (0.13
+/- 0.09 vs 0.31 +/- 0.12, P = 0.029; 0.32 +/- 0.24 vs 0.37 +/- 0.13, P = 0.034,
respectively). CONCLUSION: Patients with H. pylori following subtotal gastrectomy
had a similar eradication rate to patients with an intact stomach. H. pylori
eradication is recommended after subtotal gastrectomy.
PMID- 25852280
TI - Is endoscopic submucosal dissection safe for papillary adenocarcinoma of the
stomach?
AB - AIM: To identify the clinicopathological predictors of lymph node (LN) metastasis
and evaluate the outcomes of endoscopic submucosal dissection (ESD) in papillary
adenocarcinoma-type early gastric cancers (EGCs). METHODS: From January 2005 to
May 2013, 49 patients who underwent surgical operation and 24 patients who
underwent ESD for papillary adenocarcinoma-type EGC were enrolled to identify
clinicopathological characteristics and predictive factors of LN metastasis and
to evaluate the outcomes of ESD for papillary adenocarcinoma-type EGC. RESULTS:
Most papillary adenocarcinoma-type EGCs were located in the lower third of the
stomach and had an elevated macroscopic shape. The overall prevalence of LN
metastasis was 18.3% (9/49). The presence of lymphovascular invasion was found to
be a predictor of LN metastasis (P = 0.016). According to current indication
criteria of ESD, 6 and 11 of the 49 patients had absolute and expanded
indications for ESD, respectively. Two patients (11.8%) with expanded indication
for ESD had LN metastasis. Of the 24 patients who underwent ESD, 13 (54%)
achieved out-of-ESD indication, with 9 of those 13 patients undergoing surgical
operation due to non-curative resection. CONCLUSION: The use of ESD should be
carefully considered for papillary adenocarcinoma-type EGC with suspected ESD
indication after pre-treatment work-up because of the higher frequency of LN
metastasis and additional surgeries.
PMID- 25852281
TI - Differentiation of acute and chronic hepatitis B in IgM anti-HBc positive
patients.
AB - AIM: To identify the factors that differentiate acute hepatitis B (AHB) from
chronic hepatitis B with acute exacerbation (CHB-AE). METHODS: From 2004 to 2013,
a total of 82 patients (male n = 52, 63.4%; female n = 30, 36.6%) with clinical
features of acute hepatitis with immunoglobulin M antibodies to the hepatitis B
core antigen (IgM anti-HBc) were retrospectively enrolled and divided into two
groups; AHB (n = 53) and CHB-AE (n = 29). The AHB group was defined as patients
without a history of hepatitis B virus (HBV) infection before the episode and
with loss of hepatitis B surface antigen within 6 mo after onset of acute
hepatitis. Biochemical and virological profiles and the sample/cutoff (S/CO)
ratio of IgM anti-HBc were compared to determine the differential diagnostic
factors. RESULTS: The multivariate analysis demonstrated that, the S/CO ratio of
IgM anti-HBc and HBV DNA levels were meaningful factors. The S/CO ratio of IgM
anti-HBc was significantly higher in the AHB group, while the HBV DNA level was
significantly higher in the CHB-AE group. The optimal cutoff values of IgM anti
HBc and HBV DNA levels for differentiating the two conditions were 8 S/CO ratio
and 5.5 log10 IU/mL, respectively. The sensitivity and specificity were 96.2% and
89.7% for the S/CO ratio of IgM anti-HBc and 81.1% and 72.4% for HBV DNA levels,
respectively. The area under receiver operating characteristic curves of both the
S/CO ratio of IgM anti-HBc and HBV DNA levels were not significantly different
(0.933 vs 0.844, P = 0.105). When combining IgM anti-HBc and HBV DNA, the
diagnostic power significantly improved compared to HBV DNA alone (P = 0.0056).
The combination of these factors yielded a sensitivity and specificity of 98.1%
and 86.2%, respectively. CONCLUSION: The combination of the S/CO ratio of IgM
anti-HBc and HBV DNA levels was a useful tool for differentiating AHB from CHB-AE
in patients with positive IgM anti-HBc.
PMID- 25852282
TI - Methylation of IRAK3 is a novel prognostic marker in hepatocellular carcinoma.
AB - AIM: To examine the methylation levels of interleukin-1 receptor-associated
kinase 3 (IRAK3) and GLOXD1 and their potential clinical applications in
hepatocellular carcinoma (HCC). METHODS: mRNA expression and promoter methylation
of IRAK3 and GLOXD1 in HCC cells were analyzed by reverse transcription
polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP),
respectively. Using pyrosequencing results, we further established a quantitative
MSP (Q-MSP) system for the evaluation of IRAK3 and GLOXD1 methylation in 29
normal controls and 160 paired HCC tissues and their adjacent nontumor tissues.
We also calculated Kaplan-Meier survival curves to determine the applications of
gene methylation in the prognosis of HCC. RESULTS: IRAK3 and GLOXD1 expression
was partially restored in several HCC cell lines after treatment with 5-aza-2'
deoxycytidine (DNA methyltransferase inhibitor; 5DAC). A partial decrease in the
methylated band was also observed in the HCC cell lines after 5DAC treatment.
Using GLOXD1 as an example, we found a significant correlation between the data
obtained from the methylation array and from pyrosequencing. The methylation
frequency of IRAK3 and GLOXD1 in HCC tissues was 46.9% and 63.8%, respectively.
Methylation of IRAK3 was statistically associated with tumor stage. Moreover, HCC
patients with IRAK3 methylation had a trend toward poor 3-year disease-free
survival (P < 0.05). CONCLUSION: IRAK3 and GLOXD1 were frequently methylated in
HCC tissues compared to normal controls and nontumor tissues. IRAK3 methylation
was associated with tumor stage and poor prognosis of patients. These data
suggest that IRAK3 methylation is a novel prognostic marker in HCC.
PMID- 25852284
TI - Endoscopic transpancreatic septotomy as a precutting technique for difficult bile
duct cannulation.
AB - AIM: To evaluate the technique of transpancreatic septotomy (TS) for cannulating
inaccessible common bile ducts in endoscopic retrograde cholangiopancreatography
(ERCP). METHODS: Between May 2012 and April 2013, 1074 patients were referred to
our department for ERCP. We excluded 15 patients with previous Billroth II
gastrectomy, Roux-en-Y anastomosis, duodenal stenosis, or duodenal papilla tumor.
Among 1059 patients who underwent ERCP, there were 163 patients with difficult
bile duct cannulation. Pancreatic guidewire or pancreatic duct plastic stent
assistance allowed for successful ERCP completion in 94 patients. We
retrospectively analyzed clinical data from 69 failed patients (36
transpancreatic septotomies and 33 needle-knife sphincterotomies). RESULTS: Of
the 69 patients who underwent precut papillotomy, common bile duct cannulation
was successfully achieved in 67. The success rates in the TS and needle knife
sphincterotomy (NKS) groups were 97.2% (35/36) and 96.9% (32/33), respectively,
which were not significantly different (P > 0.05). Complications occurred in 11
cases, including acute pancreatitis (n = 6), bleeding (n = 2), and cholangitis (n
= 3). The total frequency of complications in the TS group was lower than that in
the NKS group (8.3% vs 24.2%, P < 0.05). CONCLUSION: Pancreatic guidewire or
pancreatic duct plastic stent assistance improves the success rate of selective
bile duct cannulation in ERCP. TS and NKS markedly improve the success rate of
selective bile duct cannulation in ERCP. TS precut is safer as compared with NKS.
PMID- 25852283
TI - Oxaliplatin and 5-fluorouracil hepatic infusion with lipiodolized
chemoembolization in large hepatocellular carcinoma.
AB - AIM: To investigate transarterial chemoembolization (TACE) with hepatic infusion
of oxaliplatin and 5-fluorouracil and Lipiodol chemoembolization in large
hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 132
patients with unresectable HCCs larger than 10 cm were treated with hepatic
infusion of oxaliplatin and 5-fluorouracil followed by Lipiodol
chemoembolization. The primary endpoint was overall survival (OS). Sixteen-week
disease-control rate, time to progression (TTP), and major complications were
also studied. Univariate and multivariate analyses were performed to identify
prognostic factors affecting OS and TTP. RESULTS: A total of 319 procedures were
performed in the 132 patients. Eleven (8.3%) patients received radical resection
following TACE treatment (median time to initial TACE 4.3 +/- 2.3 mo). The median
OS and TTP were 10.3 and 3.0 mo respectively, with a 50.0% 16-wk disease-control
rate. Major complications were encountered in 6.0% (8/132) of patients following
TACE and included serious jaundice in 1.5% (2/132) patients, aleukia in 1.5%
(2/132), and hepatic failure in 3.0% (4/132). One patient died within one month
due to serious hepatic failure and severe sepsis after receiving the second TACE.
The risk factor associated with TTP was baseline alpha-fetoprotein level, and
vascular invasion was an independent factor related to OS. CONCLUSION: Hepatic
infusion of oxaliplatin and 5-fluorouracil followed by lipiodolized
chemoembolization is a safe and promising treatment for patients with HCCs larger
than 10 cm in diameter.
PMID- 25852285
TI - Decreased STAT4 indicates poor prognosis and enhanced cell proliferation in
hepatocellular carcinoma.
AB - AIM: To investigate the role of signal transduction and activation of
transcription 4 (STAT4) in the development and progression of human
hepatocellular carcinoma (HCC). METHODS: Recent genetic investigations have
identified that a genetic variant of STAT4 is associated with hepatitis B virus
(HBV)-related HCC. The level of STAT4 in 90 HCC patients was examined via Western
blot and immunohistochemical analyses. The correlation between STAT4 expression
and the clinicopathological characteristics of the patients was analyzed. The
level of STAT4 expression in the HCC liver tissues was significantly lower than
that in the non-HCC liver tissues and correlated with tumor size, histological
grade of HCC and serum hepatitis B surface antigen level in HCC patients. The
data were statistically analyzed using SPSS. Furthermore, siRNA oligos targeting
STAT4 were employed to investigate the influence of STAT4 RNA interference on HCC
cell physiology. Based on Cell Counting Kit-8 and flow cytometric assays, we
found that depletion of STAT4 expression significantly enhanced the proliferation
of L02 cells. RESULTS: STAT4 protein expression was significantly lower in HCC
tissues than in normal liver tissues. Immunohistochemistry followed by
statistical analysis revealed that the expression of STAT4 negatively correlated
with Ki67 expression (r = 0.851; P < 0.05) and positively correlated with maximal
tumor size (P < 0.05), HBV (P = 0.012) and histological grade (P < 0.05). Kaplan
Meier analysis revealed significant differences in the survival curves between
HCC patients expressing low and high levels of STAT4 and Ki67 (P < 0.05). Based
on a multivariate Cox proportional hazard model, STAT4 expression was an
independent prognostic indicator for HCC patients who underwent curative
resection. In vitro, following the release of L02 cell lines from serum
starvation, the expression of STAT4 was downregulated, and transfection of L02
cells with siRNA targeting STAT4 inhibited cell proliferation. CONCLUSION: Our
data indicate that STAT4 may inhibit HCC development by modulating HCC cell
proliferation.
PMID- 25852286
TI - Importance of reporting segmental bowel preparation scores during colonoscopy in
clinical practice.
AB - AIM: To evaluate the impact of reporting bowel preparation using Boston Bowel
Preparation Scale (BBPS) in clinical practice. METHODS: The study was a
prospective observational cohort study which enrolled subjects reporting for
screening colonoscopy. All subjects received a gallon of polyethylene glycol as
bowel preparation regimen. After colonoscopy the endoscopists determined quality
of bowel preparation using BBPS. Segmental scores were combined to calculate
composite BBPS. Site and size of the polyps detected was recorded. Pathology
reports were reviewed to determine advanced adenoma detection rates (AADR).
Segmental AADR's were calculated and categorized based on the segmental BBPS to
determine the differential impact of bowel prep on AADR. RESULTS: Three hundred
and sixty subjects were enrolled in the study with a mean age of 59.2 years,
36.3% males and 63.8% females. Four subjects with incomplete colonoscopy due BBPS
of 0 in any segment were excluded. Based on composite BBPS subjects were divided
into 3 groups; Group-0 (poor bowel prep, BBPS 0-3) n = 26 (7.3%), Group-1
(Suboptimal bowel prep, BBPS 4-6) n = 121 (34%) and Group-2 (Adequate bowel prep,
BBPS 7-9) n = 209 (58.7%). AADR showed a linear trend through Group-1 to 3; with
an AADR of 3.8%, 14.8% and 16.7% respectively. Also seen was a linear increasing
trend in segmental AADR with improvement in segmental BBPS. There was statistical
significant difference between AADR among Group 0 and 2 (3.8% vs 16.7%, P <
0.05), Group 1 and 2 (14.8% vs 16.7%, P < 0.05) and Group 0 and 1 (3.8% vs 14.8%,
P < 0.05). chi(2) method was used to compute P value for determining statistical
significance. CONCLUSION: Segmental AADRs correlate with segmental BBPS. It is
thus valuable to report segmental BBPS in colonoscopy reports in clinical
practice.
PMID- 25852287
TI - Rectal tone and compliance affected in patients with fecal incontinence after
fistulotomy.
AB - AIM: To investigate the anal sphincter and rectal factors that may be involved in
fecal incontinence that develops following fistulotomy (FIAF). METHODS: Eleven
patients with FIAF were compared with 11 patients with idiopathic fecal
incontinence and with 11 asymptomatic healthy subjects (HS). All of the study
participants underwent anorectal manometry and a barostat study (rectal
sensitivity, tone, compliance and capacity). The mean time since surgery was 28
+/- 26 mo. The postoperative continence score was 14 +/- 2.5 (95%CI: 12.4-15.5,
St Mark's fecal incontinence grading system). RESULTS: Compared with the HS, the
FIAF patients showed increased rectal tone (42.63 +/- 27.69 vs 103.5 +/- 51.13, P
= 0.002) and less rectal compliance (4.95 +/- 3.43 vs 11.77 +/- 6.9, P = 0.009).
No significant differences were found between the FIAF patients and the HS with
respect to the rectal capacity; thresholds for the non-noxious stimuli of first
sensation, gas sensation and urge-to-defecate sensation or the noxious stimulus
of pain; anal resting pressure or squeeze pressure; or the frequency or
percentage of relaxation of the rectoanal inhibitory reflex. No significant
differences were found between the FIAF patients and the patients with idiopathic
fecal incontinence. CONCLUSION: In patients with FIAF, normal motor anal
sphincter function and rectal sensitivity are preserved, but rectal tone and
compliance are impaired. The results suggest that FIAF is not due to alterations
in rectal sensitivity and that the rectum is more involved than the anal
sphincters in the genesis of FIAF.
PMID- 25852288
TI - Interferon-lambda-related genes and therapeutic response in Chinese hepatitis C
patients.
AB - AIM: To determine the association between rapid viral response and IL28B, IL28RA,
IL10RB and MxA polymorphisms in the Chinese Han population. METHODS: The study
cohort consisted of 238 chronic hepatitis C patients treated with interferon
(IFN)-alpha-2b and ribavirin. Six single nucleotide polymorphisms were genotyped
using the ABI TaqMan allelic discrimination assay. Biochemical indices were
measured at baseline. Serum hepatitis C virus (HCV) RNA was detected at weeks 0,
4, 12 and 24 of therapy. RESULTS: Only IL28B rs12980275 was associated with
treatment response in the Chinese Han population. Patients carrying AG/GG
genotypes had a reduced rapid viral response compared with patients carrying the
AA genotype (additive model: adjusted OR = 0.43, 95%CI: 0.24-0.75). It took less
time for patients with the AA genotype to achieve a viral load < 500 copies/mL
(log-rank test, P = 0.004). In addition, the protective effect of genotype AA was
independent of baseline viral load. HCV genotype, and baseline white blood cell
count, alpha-fetoprotein and viral load might also help predict treatment
response. The area under the receiver-operating characteristic curve was 0.726.
CONCLUSION: IL28B rs12980275 AA genotype is a strong predictor of positive
response to IFN therapy in Chinese Han patients with hepatitis C.
PMID- 25852289
TI - Endoscopic ultrasound elastography strain histograms in the evaluation of
patients with pancreatic masses.
AB - AIM: To investigate the accuracy of the strain histogram endoscopic ultrasound
(EUS)-based method for the diagnostic differentiation of patients with pancreatic
masses. METHODS: In a prospective single center study, 149 patients were
analyzed, 105 with pancreatic masses and 44 controls. Elastography images were
recorded using commercially available ultrasound equipment in combination with
EUS linear probes. Strain histograms (SHs) were calculated by machine integrated
software in regions of interest and mean values of the strain histograms were
expressed as Mode 1 (over the mass) and Mode 2 (over an adjacent part of
pancreatic tissue, representing the reference area). The ratio between Mode 2 and
Mode 1 was calculated later, representing a new variable, the strain histogram
ratio. After the final diagnosis was established, two groups of patients were
formed: a pancreatic cancer group with positive cytology achieved by fine needle
aspiration puncture or histology after surgery (58 patients), and a mass-forming
pancreatitis group with negative cytology and follow-up after 3 and 6 mo (47
patients). All statistical analyses were conducted in SPSS 14.0 (SPSS Inc.,
Chicago, IL, United States). RESULTS: Results were obtained with software for
strain histograms with reversed hue scale (0 represents the hardest tissue
structure and 255 the softest). Based on the receiver operating characteristics
(ROC) curve coordinates, the cut-off point for Mode 1 was set at the value of 86.
Values under the cut-off point indicated the presence of pancreatic malignancy.
Mode 1 reached 100% sensitivity and 45% specificity with overall accuracy of 66%
(95%CI: 61%-66%) in detection of pancreatic malignant tumors among the patients
with pancreatic masses. The positive and negative predictive values were 54% and
100%, respectively. The cut-off for the new calculated variable, the SH ratio,
was set at the value 1.153 based on the ROC curve coordinates. Values equal or
above the cut-off value were indicative of pancreatic malignancy. The SH ratio
reached 98% sensitivity, 50% specificity and an overall accuracy of 69% (95%CI:
63%-70%). The positive and negative predictive values were 92% and 100%,
respectively. CONCLUSION: SH showed high sensitivity in pancreatic malignant
tumor detection but disappointingly low specificity. Slight improvements in
specificity and accuracy were achieved using the SH ratio.
PMID- 25852290
TI - PERFACT procedure: a new concept to treat highly complex anal fistula.
AB - AIM: To check the efficacy of the PERFACT procedure in highly complex fistula-in
ano. METHODS: The PERFACT procedure (proximal superficial cauterization, emptying
regularly fistula tracts and curettage of tracts) entails two steps: superficial
cauterization of mucosa at and around the internal opening and keeping all the
tracts clean. The principle is to permanently close the internal opening by
granulation tissue. This is achieved by superficial electrocauterization at and
around the internal opening and subsequently allowing the wound to heal by
secondary intention. Along with this, all the tracts are curetted and it is
ensured that they remain empty and clean in the postoperative period until they
heal completely. The latter step also facilitates the closure of the internal
opening by preventing collected fluid in the tracts from entering the internal
opening and thus not letting it close. Objective incontinence scoring was done
preoperatively and 3 mo after the operation. RESULTS: Fifty-one patients with
complex fistula-in-ano were prospectively enrolled. The median follow-up was 9 mo
(5-14 mo). The mean age was 42.7 +/- 11.3 years. Male:female ratio was 43:8.
Fistula was recurrent in 76.5% (39/51), horseshoe in 50.1% (26/51), had multiple
tracts in 52.9% (27/51), had an associated abscess in 41.2% (21/51), was anterior
in 33.3% (17/51), the internal opening was not found in 15.7% (8/51) and 9.8%
(5/51) of fistulas had a supralevator extension. Seven patients were excluded (5
lost to follow up, 2 with tuberculosis leading to/associated with fistula-in
ano). The success rate was 79.5% (35/44) and the recurrence rate was 20.5%
(9/44). Out of these recurrences, three underwent reoperation (2 PERFACT
procedure, 1 fistulotomy) and all three were successful. Thus, the overall
success rate was 86.4%. The only complication was a non-healing tract in 9.1%
(4/44) of patients. There was no significant change in objective incontinence
scores three months after the operation. The pain was minimal, with all patients
resuming their normal activities within 72 h of the operation. CONCLUSION: The
PERFACT procedure is a new effective method for complex fistula-in-ano, effective
even in fistula associated with abscess, supralevator fistula-in-ano and where
the internal opening is non-localizable.
PMID- 25852291
TI - Lower gastrointestinal bleeding: role of 64-row computed tomographic angiography
in diagnosis and therapeutic planning.
AB - AIM: To determine the value of computed tomographic angiography (CTA) for
diagnosis and therapeutic planning in lower gastrointestinal (GI) bleeding.
METHODS: Sixty-three consecutive patients with acute lower GI bleeding underwent
CTA before endovascular or surgical treatment. CTA was used to determine whether
the lower GI bleeding was suitable for endovascular treatment, surgical
resection, or conservative treatment in each patient. Treatment planning with CTA
was compared with actual treatment decisions or endovascular or surgical
treatment that had been carried out in each patient based on CTA findings.
RESULTS: 64-row CTA detected active extravasation of contrast material in 57
patients and six patients had no demonstrable active bleeding, resulting in an
accuracy of 90.5% in the detection of acute GI bleeding (57 of 63). In three of
the six patients with no demonstrable active bleeding, active lower GI bleeding
recurred within one week after CTA, and angiography revealed acute bleeding. The
overall location-based accuracy, sensitivity, specificity, positive predictive
value (PPV) and negative predictive value (NPV) for the detection of GI bleeding
by 64-row CTA were 98.8% (249 of 252), 95.0% (57 of 60), 100% (192 of 192), 100%
(57 of 57), and 98.5% (192 of 195), respectively. Treatment planning was
correctly established on the basis of 64-row CTA with an accuracy, sensitivity,
specificity, PPV and NPV of 98.4% (248 of 252), 93.3% (56 of 60), 100% (192 of
192), 100% (56 of 56), and 97.5% (192 of 196), respectively, in a location-based
evaluation. CONCLUSION: 64-row CTA is safe and effective in making decisions
regarding treatment, without performing digital subtraction angiography or
surgery, in the majority of patients with lower GI bleeding.
PMID- 25852292
TI - Osteoporosis and bone fractures in alcoholic liver disease: a meta-analysis.
AB - AIM: To evaluate the association between alcoholic liver disease (ALD) and bone
fractures or osteoporosis. METHODS: Non-randomized studies were identified from
databases (PubMed, EMBASE, and the Cochrane Library). The search was conducted
using Boolean operators and keywords, which included "alcoholic liver diseases",
"osteoporosis", or "bone fractures". The prevalence of any fractures or
osteoporosis, and bone mineral density (BMD) were extracted and analyzed using
risk ratios and standardized mean difference (SMD). A random effects model was
applied. RESULTS: In total, 15 studies were identified and analyzed. Overall, ALD
demonstrated a RR of 1.944 (95%CI: 1.354-2.791) for the development of bone
fractures. However, ALD showed a RR of 0.849 (95%CI: 0.523-1.380) for the
development of osteoporosis. BMD was not significantly different between the ALD
and control groups, although there was a trend toward lower BMD in patients with
ALD (SMD in femur-BMD: -0.172, 95%CI: -0.453-0.110; SMD in spine-BMD: -0.169,
95%CI: -0.476-0.138). Sensitivity analyses showed consistent results. CONCLUSION:
Current publications indicate significant associations between bone fractures and
ALD, independent of BMD or the presence of osteoporosis.
PMID- 25852294
TI - Urea cycle disorders: a case report of a successful treatment with liver
transplant and a literature review.
AB - The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders
(UCDs) include a variety of genetic defects, which lead to inefficient urea
synthesis. Elevated blood ammonium level is usually dominant in the clinical
pattern and the primary manifestations affect the central nervous system. Herein,
we report the case of a 17-year-old girl who was diagnosed with UCD at the age of
3. Despite a controlled diet, she was hospitalized several times for acute
attacks with recurrent life risk. She came to our attention for a hyperammonemic
episode. We proposed an orthotopic liver transplant (OLT) as a treatment; the
patient and her family were in complete agreement. On February 28, 2007, she
successfully received a transplant. Following the surgery, she has remained well,
and she is currently leading a normal life. Usually for UCDs diet plays the
primary therapeutic role, while OLT is often considered as a last resort. Our
case report and the recent literature data on the quality of life and prognosis
of traditionally treated patients vs OLT patients, support OLT as a primary
intervention to prevent life-threatening acute episodes and chronic mental
impairment.
PMID- 25852293
TI - Resolution of Crohn's disease and complex regional pain syndrome following
treatment of paratuberculosis.
AB - A cohort of family members with various chronic diseases including Crohn's
disease, asthma, complex regional pain syndrome, hypothyroidism, type 1 diabetes
mellitus, and lymphangiomatosis and/or evidence of infection by Mycobacterium
avium subsp. paratuberculosis (MAP) are described in this series of case reports.
MAP was cultured from the blood of three members affected by the first five
diseases and there was accompanying elevated anti-MAP IgG in two members. The
patient affected by the sixth disease has a markedly elevated anti-MAP titer. The
two patients affected by the first four diseases have been treated with a
combination of anti-MAP antibiotics and ultraviolet blood irradiation therapy
with resolution of the disease symptomatology and inability to culture MAP in
post treatment blood samples. These case reports of patients with MAP infections
provide supportive evidence of a pathogenic role of MAP in humans.
PMID- 25852296
TI - Treatment of Crohn's disease and familial Mediterranean fever by leukopheresis:
single shot for two targets.
AB - Coexistence of Crohn's disease (CD) and familial Mediterranean fever (FMF) is a
rare condition and knowledge about this clinical situation is limited with a few
case reports in the literature. The treatment of both diseases depends on their
individual therapies. However, it is very hard to deal with this coexistence when
CD is refractory to standard therapies. Ongoing activity of CD triggers the
clinical attacks of FMF and the symptoms like abdominal pain interfere with both
disease presentations which can cause problems about diagnostic and therapeutic
approach. The main therapeutic agent for FMF is colchicine and diarrhea is the
most common side effect of this drug. This side effect also causes problems about
management of these diseases when both of them are clinically active. Here we
report probably the first case in the literature with coexisting CD and FMF who
was successfully treated by leukopheresis since he was refractory to conventional
therapies for CD.
PMID- 25852295
TI - Gastroenterology case report of mesalazine-induced cardiopulmonary
hypersensitivity.
AB - Mesalazine is a 5-aminosalicylic acid derivative that has been widely used to
treat patients with inflammatory bowel disease. Accumulating evidence indicates
that mesalazine has a very low rate of adverse drug reactions and is well
tolerated by patients. However, a few cases of pulmonary and cardiac disease
related to mesalazine have been reported in the past, though infrequently,
preventing clinicians from diagnosing the conditions early. We describe the case
of a 32-year-old man with ulcerative colitis who was admitted with a two-month
history of persistent fever following mesalazine treatment initiated 14 mo
earlier. At the time of admission, mesalazine dose was increased from 1.5 to 3.0
g/d, and antibiotic therapy was started with no improvement. Three weeks after
admission, the patient developed dyspnea, non-productive cough, and chest pain.
Severe eosinophilia was detected in laboratory tests, and a computed tomography
scan revealed interstitial infiltrates in both lungs, as well as a large
pericardial effusion. The bronchoalveolar lavage reported a CD4/CD8 ratio of 0.5,
and an increased eosinophil count. Transbronchial biopsy examination showed a
severe eosinophilic infiltrate of the lung tissue. Mesalazine-induced
cardiopulmonary hypersensitivity was suspected after excluding other possible
etiologies. Consequently, mesalazine treatment was suspended, and corticosteroid
therapy was initiated, resulting in resolution of symptoms and radiologic
abnormalities. We conclude that mesalazine-induced pulmonary and cardiac
hypersensitivity should always be considered in the differential diagnosis of
unexplained cardiopulmonary symptoms and radiographic abnormalities in patients
with inflammatory bowel disease.
PMID- 25852297
TI - Adenocarcinoma arising from heterotopic pancreas at the third portion of the
duodenum.
AB - A 62-year-old Japanese man presented to our hospital with a history of weight
loss of 6 kg in 4 mo. Imaging examinations revealed a tumor located on the third
portion of the duodenum with stenosis. We suspected duodenal carcinoma and
performed pancreas-preserving segmental duodenectomy. Adenocarcinoma arising from
a heterotopic pancreas at the third portion of the duodenum was finally diagnosed
by immunohistochemical staining. Malignant transformation in the duodenum arising
from a heterotopic pancreas is extremely rare; to our knowledge, only 13 cases
have been reported worldwide, including the present case. The most common
location of malignancy is the proximal duodenum at the first and descending
portion. Herein, we describe the first case of adenocarcinoma arising from a
heterotopic pancreas, which was located in the third portion of the duodenum,
with a review of the literature.
PMID- 25852298
TI - Lymphoepithelioma-like cholangiocarcinoma: a mimic of hepatocellular carcinoma on
imaging features.
AB - Primary lymphoepithelioma-like carcinoma in the liver is extremely rare. A few
cases of lymphoepithelioma-like cholangiocarcinoma have been reported, but few
radiologic features were described. We reviewed 23 cases of lymphoepithelioma
like cholangiocarcinoma reported between 1996 and 2014 and describe a rare case
of a 35-year-old woman in our hospital who was diagnosed with lymphoepithelioma
like cholangiocarcinoma of the liver and was a hepatitis B carrier. The tumor
(1.6 cm) in our patient appeared to be hypoechoic in sonographic images and
hypodense in computed tomography (CT) images. In addition, it was homogeneous
hypointense in T1-weighted magnetic resonance (MR) images (MRI) and hyperintense
in T2-weighted MRI. Dynamic gadolinium-enhanced MRI showed typical image pattern
of hepatocellular carcinoma (HCC). The patient underwent a laparoscopic left
hepatic lobectomy, and the resected tumor consisted of well-differentiated
glandular cells with extensive lymphocytic infiltration that were immunoreactive
to CK (AE1/AE3), CD3, and CD20. In addition, the tumor was positive for Epstein
Barr virus-encoded RNA in situ hybridization. Finally, lymphoepithelioma-like
cholangiocarcinoma was diagnosed. In previous studies, the incidence is highest
among middle-aged people. Most tumors appeared to be hypodense with either
hypovascular or hypervascular patterns in CT images. This case report is the
first study to address sonography, CT, and MRI observations and delineate
pathologic correlations. We suggest that the imaging pattern of lymphoepithelioma
like cholangiocarcinoma, either the typical cholangiocarcinoma pattern or a mimic
of HCC, should be considered in the differential lists for HCC.
PMID- 25852299
TI - Segmental small bowel necrosis associated with antiphospholipid syndrome: a case
report.
AB - Antiphospholipid syndrome is a multi-system disease characterized by the
formation of thromboembolic complications and/or pregnancy morbidity, and with
persistently increased titers of antiphospholipid antibodies. We report the case
of a 50-year-old, previously healthy man who presented with fever and new-onset,
dull abdominal pain. A contrast-enhanced computed tomography scan showed
segmental small bowel obstruction, for which an emergency laparotomy was
performed. Histopathologic examination of resected tissues revealed multiple
intestinal and mesenteric thromboses of small vessels. Laboratory tests for serum
antiphospholipid (anticardiolipin IgM) and anti-beta2-glycoprotein I antibodies
were positive. Despite proactive implementation of anticoagulation, steroid, and
antibiotic therapies, the patient's condition rapidly deteriorated, and he died
22 d after admission. This case highlights that antiphospholipid syndrome should
be suspected in patients with unexplainable ischemic bowel and intestinal
necrosis presenting with insidious clinical features that may be secondary to the
disease, as early diagnosis is critical to implement timely treatments in order
to ameliorate the disease course.
PMID- 25852300
TI - Lower folate levels in gastric cancer: is it a cause or a result?
AB - Folate deficiency and its association with cancer have been studied in the
literature, but its clinical impact is still unknown. Folate deficiency and its
result on gastric cancer is a mysterious part of oncology, with ongoing studies
hopefully clarifying its impact on gastric cancer management. Lee et al studied
folate deficiency and its impact on staging and clinical results. Here we try to
contribute to the field by expressing our own thoughts about the paper.
PMID- 25852301
TI - Temporal trends and current practice patterns for intraoperative ventilation at
U.S. academic medical centers: a retrospective study.
AB - BACKGROUND: Lung protective ventilation strategies utilizing lower tidal volumes
per predicted body weight (PBW) and positive end-expiratory pressure (PEEP) have
been suggested to be beneficial in a variety of surgical populations. Recent
clinical studies have used control groups ventilated with high tidal volumes
without PEEP based on the assumption that this reflects current clinical
practice. We hypothesized that ventilation strategies have changed over time,
that most anesthetics in U.S. academic medical centers are currently performed
with lower tidal volumes, and that most receive PEEP. METHODS: Intraoperative
data were pooled for adults undergoing general anesthesia with tracheal
intubation. Median tidal volumes per kilogram of PBW were categorized as > 10, 8
10 and < 8 mL per kg of PBW. The percentages of cases in 2013 that were performed
with median tidal volumes < 8 mL per kg of PBW and PEEP were determined. As a
secondary analysis, a proportional odds model using institution, year, height,
weight and gender determined the relative associations of these factors using
categorical and interquartile odds ratios. RESULTS: 295,540 cases were analyzed
from 5 institutions over a period of 10 years. In 2013, 59.3% of cases used
median tidal volumes < 8 mL per kg of PBW, 83.3% used PEEP, and 51.0% used both.
Of those cases with PEEP, 60.9% used a median pressure of >= 5 cmH2O. Predictors
of lower categories of tidal volumes included height (odds ratio (OR) 10.83, 95%
confidence interval [10.50, 11.16]), institution (lowest OR 0.98 [0.96, 1.00],
highest OR 9.63 [9.41, 9.86]), year (lowest OR 1.32 [1.21, 1.44], highest OR 6.31
[5.84, 6.82]), male gender (OR 1.10 [1.07, 1.12]), and weight (OR 0.30 [0.29,
0.31]). CONCLUSION: Most general anesthetics with tracheal intubation at the
institutions surveyed are currently performed with a median tidal volume < 8 mL
per kg of PBW, most are managed with PEEP of >= 5 cmH2O and approximately half
utilize both. Given the diversity of the institutions included, this is likely
reflective of practice in U.S. academic medical centers. The utilization of
higher tidal volumes without PEEP in control groups for clinical research studies
should be reconsidered.
PMID- 25852302
TI - Bim and VDAC1 are hierarchically essential for mitochondrial ATF2 mediated cell
death.
AB - BACKGROUND: ATF2 mediated cytochrome c release is the formation of a channel with
some unknown factors larger than that of the individual proteins. BHS-only
proteins (BH3s), such as Bim, could induce BAX and VDAC, forming a new channel.
According to this facts, we can speculated that there is possible signal
relationship with BH3s and ATF2, which is associated with mitochondrial-based
death programs. METHODS: The growth inhibitory effects of mitochondrial ATF2 were
tested in cancer cell lines B16F10, A549, EG7, and LL2. Apoptosis was measured by
flow cytometry. The effects of ATF2 and levels of apoptosis regulatory proteins
were measured by Western blotting. The interaction of proteins were evaluated by
immunoprecipitation analysis. The in vivo antitumor activity of mitochondrial
ATF2 were tested in xenograft B16F10 models. RESULTS: Genotoxic stress enabled
mitochondrial ATF2 accumulation, perturbing the HK1-VDAC1 complex, increasing
mitochondrial permeability, and promoting apoptosis. ATF2 inhibition strongly
reduced the conformational activation of Bim, suggesting that Bim acts downstream
of ATF2. Although Bim downregulation had no effect on ATF2 activation, Bim
knockdown abolished VDAC1 activation; the failure of VDAC1 activation in Bim
depleted cells could be reversed by the BH3-only protein mimic ABT-737. We also
demonstrate that silencing of ATF2 in B16F10 cells increases both the incidence
and prevalence of tumor xenografts in vivo, whereas stably mitochondrial ATF2
transfection inhibited B16F10 tumor xenografts growth. CONCLUSIONS: Altogether,
these results show that ATF2 is a component of the apoptosis machinery that
involves a hierarchical contribution of ATF2, Bim, and VDAC1. Our data offer new
insight into the mechanism of mitochondrial ATF2 in mitochondrial apoptosis.
PMID- 25852304
TI - Propargylic substitution reactions with various nucleophilic compounds using
efficient and recyclable mesoporous silica spheres embedded with FeCo/graphitic
shell nanocrystals.
AB - Phosphomolybdic acid (PMA, H3PMo12O40) functioned as a catalyst for reactions of
secondary propargylic alcohols and nucleophiles. Highly stable and magnetically
recyclable mesoporous silica spheres (MMS) embedded with FeCo-graphitic carbon
shell nanocrystals (FeCo/GC@MSS) were fabricated by a modified Stober process and
chemical vapor deposition (CVD) method. The FeCo/GC@MSS were loaded with
phosphomolybdic acid (PMA@FeCo/GC@MSS), and their catalytic activity was
investigated. Propargylic reactions of 1,3-diphenyl-2-propyn-1-ol with a wide
range of nucleophiles bearing activating substituents were catalyzed under mild
conditions. It was found that the MMS possess mesoporosities and have enough
inner space to load FeCo and phosphomolybdic acid. The FeCo/GC@MSS were found to
be chemically stable against acid etching and oxidation. This suggests that the
nanocrystals can be used as a support for an acid catalyst. Moreover, the
magnetic property of the nanocrystals enabled the facile separation of catalysts
from the products.
PMID- 25852303
TI - Differential effects of dopamine signalling on long-term memory formation and
consolidation in rodent brain.
AB - BACKGROUND: Using auditory discrimination learning in gerbils, we have previously
shown that activation of auditory-cortical D1/D5 dopamine receptors facilitates
mTOR-mediated, protein synthesis-dependent mechanisms of memory consolidation and
anterograde memory formation. To understand molecular mechanisms of this
facilitatory effect, we tested the impact of local pharmacological activation of
different D1/D5 dopamine receptor signalling modes in the auditory cortex. To
this end, protein patterns in soluble and synaptic protein-enriched fractions
from cortical, hippocampal and striatal brain regions of ligand- and vehicle
treated gerbils were analysed by 2D gel electrophoresis and mass spectrometry 24
h after intervention. RESULTS: After auditory-cortical injection of SKF38393 - a
D1/D5 dopamine receptor-selective agonist reported to activate the downstream
effectors adenylyl cyclase and phospholipase C - prominent proteomic alterations
compared to vehicle-treated controls appeared in the auditory cortex, striatum,
and hippocampus, whereas only minor changes were detectable in the frontal
cortex. In contrast, auditory-cortical injection of SKF83959 - a D1/D5 agonist
reported to preferentially stimulate phospholipase C - induced pronounced changes
in the frontal cortex. At the molecular level, we detected altered regulation of
cytoskeletal and scaffolding proteins, changes in proteins with functions in
energy metabolism, local protein synthesis, and synaptic signalling.
Interestingly, abundance and/or subcellular localisation of the predominantly
presynaptic protein alpha-synuclein displayed dopaminergic regulation. To assess
the role of alpha-synuclein for dopaminergic mechanisms of memory modulation, we
tested the impact of post-conditioning systemic pharmacological activation of
different D1/D5 dopamine receptor signalling modes on auditory discrimination
learning in alpha-synuclein-mutant mice. In C57BL/6JOlaHsd mice, bearing a
spontaneous deletion of the alpha-synuclein-encoding gene, but not in the related
substrains C57BL/6JCrl and C57BL/6JRccHsd, adenylyl cyclase-mediated signalling
affected acquisition rates over future learning episodes, whereas phospholipase C
mediated signalling affected final memory performance. CONCLUSIONS: Dopamine
signalling modes via D1/D5 receptors in the auditory cortex differentially impact
protein profiles related to rearrangement of cytomatrices, energy metabolism, and
synaptic neurotransmission in cortical, hippocampal, and basal brain structures.
Altered dopamine neurotransmission in alpha-synuclein-deficient mice revealed
that distinct D1/D5 receptor signalling modes may control different aspects of
memory consolidation.
PMID- 25852305
TI - Targeted images of KB cells using folate-conjugated gold nanoparticles.
AB - Mercaptosuccinic acid-coated gold (GM) nanoparticles were prepared and
characterized by transmission electron microscopy and dynamic light scattering.
Folic acid (F) was then conjugated to the GM to preferentially target oral
squamous cancer (KB) cells with folate receptors expressed on their membranes and
facilitate the transit of the nanoparticles across the cell membrane. Finally, a
fluorescence dye (Atto) was conjugated to the nanoparticles to visualize their
internalization into KB cells. After culture of the cells in a medium containing
GM and folate-conjugated GM (GF), the interaction of surface-modified gold
nanoparticles with KB cells was studied.
PMID- 25852306
TI - High electron mobility and low carrier concentration of hydrothermally grown ZnO
thin films on seeded a-plane sapphire at low temperature.
AB - Hydrothermal zinc oxide (ZnO) thick films were successfully grown on the chemical
vapor deposition (CVD)-grown thick ZnO seed layers on a-plane sapphire substrates
using the aqueous solution of zinc nitrate dehydrate (Zn(NO3)2). The use of the
CVD ZnO seed layers with the flat surfaces seems to be a key technique for
obtaining thick films instead of vertically aligned nanostructures as reported in
many literatures. All the hydrothermal ZnO layers showed the large grains with
hexagonal end facets and were highly oriented towards the c-axis direction.
Photoluminescence (PL) spectra of the hydrothermal layers were composed of the
ultraviolet (UV) emission (370 to 380 nm) and the visible emission (481 to 491
nm), and the intensity ratio of the former emission (I UV) to the latter emission
(I VIS) changed, depending on both the molarity of the solution and temperature.
It is surprising that all the Hall mobilities for the hydrothermal ZnO layers
were significantly larger than those for their corresponding CVD seed films. It
was also found that, for the hydrothermal films grown at 70 degrees C to 90
degrees C, the molarity dependences of I UV/I VIS resembled those of mobilities,
implying that the mobility in the film is affected by the structural defects. The
highest mobility of 166 cm(2)/Vs was achieved on the hydrothermal film with the
carrier concentration of 1.65 * 10(17) cm(-3) grown from the aqueous solution of
40 mM at 70 degrees C.
PMID- 25852307
TI - Effects of architectures and H2O2 additions on the photocatalytic performance of
hierarchical Cu2O nanostructures.
AB - Cu2O hierarchical nanostructures with different morphologies were successfully
synthesized by a solvothermal method using copper (II) nitrate trihydrate
(Cu(NO3)2?3H2O) and ethylene glycol (EG) as initial reagents. The obtained
nanostructures were characterized by X-ray diffraction (XRD), scanning electron
microscopy (SEM), Brunauer-Emmett-Teller (BET) specific surface area test, and UV
vis spectroscopy. The synthesis conditions (copper source, temperature, and
reaction time) dominated the compositions and the formation of crystals with
different morphologies. The visible light photocatalytic properties of as
prepared Cu2O nanostructures were investigated with and without hydrogen peroxide
(H2O2), and the effect of H2O2 were evaluated by monitoring the degradation of
methyl orange (MO) with various amounts of H2O2. It was revealed that the degree
of the photodegradation of MO depends on the amount of H2O2 and the morphology of
Cu2O.
PMID- 25852308
TI - Seed/catalyst-free growth of zinc oxide on graphene by thermal evaporation:
effects of substrate inclination angles and graphene thicknesses.
AB - A seed/catalyst-free growth of ZnO on graphene by thermal evaporation of Zn in
the presence of O2 gas was further studied. The effects of substrate positions
and graphene thicknesses on the morphological, structural, and optical properties
were found to be very pronounced. By setting the substrate to be inclined at 90
degrees , the growth of ZnO nanostructures, namely, nanoclusters and nanorods, on
single-layer (SL) graphene was successfully realized at temperatures of 600
degrees C and 800 degrees C, respectively. For the growth on multilayer (ML)
graphene at 600 degrees C with an inclination angle of 90 degrees , the grown
structures show extremely thick and continuous cluster structures as compared to
the growth with substrate's inclination angle of 45 degrees . Moreover, the base
of nanorod structures grown at 800 degrees C with an inclination angle of 90
degrees also become thicker as compared to 45 degrees , even though their
densities and aspect ratios were almost unchanged. Photoluminescence (PL) spectra
of the grown ZnO structures were composed of the UV emission (378-386 nm) and the
visible emission (517-550 nm), and the intensity ratio of the former emission (I
UV) to the latter emission (I VIS) changed, depending on the temperature. The
structures grown at a low temperature of 600 degrees C show the highest value of
I UV/I VIS of 16.2, which is almost two times higher than the structures grown on
SL graphene, indicating fewer structural defects. The possible growth mechanism
was proposed and described which considered both the nucleation and oxidation
processes. From the results obtained, it can be concluded that temperature below
800 degrees C, substrate position inclined at 90 degrees towards the gas flow,
and ML graphene seems to be preferable parameters for the growth of ZnO
structures by thermal evaporation because these factors can be used to overcome
the problem of graphene's oxidation that takes place during the growth.
PMID- 25852309
TI - Morphological engineering of self-assembled nanostructures at nanoscale on
faceted GaAs nanowires by droplet epitaxy.
AB - Fabrication of advanced artificial nanomaterials is a long-term pursuit to
fulfill the promises of nanomaterials and it is of utter importance to manipulate
materials at nanoscale to meet urgent demands of nanostructures with designed
properties. Herein, we demonstrate the morphological tailoring of self-assembled
nanostructures on faceted GaAs nanowires (NWs). The NWs are deposited on
different kinds of substrates. Triangular and hexagonal prism morphologies are
obtained, and their corresponding {110} sidewalls act as platforms for the
nucleation of gallium droplets (GDs). We demonstrate that the morphologies of the
nanostructures depend not only on the annealing conditions but also on the
morphologies of the NWs' sidewalls. Here, we achieve morphological engineering in
the form of novel quantum dots (QDs), 'square' quantum rings (QRs), 'rectangular'
QRs, 3D QRs, crescent-shaped QRs, and nano-antidots. The evolution mechanisms for
the peculiar morphologies of both NWs and nanostructures are modeled and
discussed in detail. This work shows the potential of combining nano-structural
engineering with NWs to achieve multifunctional properties and applications.
PMID- 25852310
TI - Gene expression profile of human lung epithelial cells chronically exposed to
single-walled carbon nanotubes.
AB - A rapid increase in utility of engineered nanomaterials, including carbon
nanotubes (CNTs), has raised a concern over their safety. Based on recent
evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle
accumulation in the deep lung without effective clearance which could interact
with local lung cells for a long period of time. Physicochemical similarities of
CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic
potential after long-term exposure, which has not been well addressed. More
studies are needed to identify and predict the carcinogenic potential and
mechanisms for promoting their safe use. Our previous study reported a long-term
in vitro exposure model for CNT carcinogenicity and showed that 6-month sub
chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant
transformation of human lung epithelial cells. In addition, the transformed cells
induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a
key characteristic of cancer cells. Although the potential role of p53 in the
transformation process was identified, the underlying mechanisms of oncogenesis
remain largely undefined. Here, we further examined the gene expression profile
by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis.
Based on differentially expressed genes, possible mechanisms of SWCNT-associated
apoptosis resistance and oncogenesis were identified, which included activation
of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for
cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes
BAX and Noxa. Activated immune responses were among the major changes of
biological function. Our findings shed light on potential molecular mechanisms
and signaling pathways involved in SWCNT oncogenic potential.
PMID- 25852311
TI - Unusual structural and electronic properties of porous silicene and germanene:
insights from first-principles calculations.
AB - Using first-principles calculations, we investigate the geometric structures and
electronic properties of porous silicene and germanene nanosheets, which are the
Si and Ge analogues of alpha-graphyne (referred to as silicyne and germanyne). It
is found that the elemental silicyne and germanyne sheets are energetically
unfavourable. However, after the C-substitution, the hybrid graphyne-like sheets
(c-silicyne/c-germanyne) possess robust energetic and dynamical stabilities.
Different from silicene and germanene, c-silicyne is a flat sheet, and c
germanyne is buckled with a distinct half-hilled conformation. Such asymmetric
buckling structure causes the semiconducting behaviour into c-germanyne. While in
c-silicyne, the semimetallic Dirac-like property is kept at the nonmagnetic
state, but a spontaneous antiferromagnetism produces the massive Dirac fermions
and opens a sizeable gap between Dirac cones. A tensile strain can further
enhance the antiferromagnetism, which also linearly modulates the gap value
without altering the direct-bandgap feature. Through strain engineering, c
silicyne can form a type-II band alignment with the MoS 2 sheet. The combined c
silicyne/MoS 2 nanostructure has a high power conversion efficiency beyond 20%
for photovoltaic solar cells, enabling a fascinating utilization in the fields of
solar energy and nano-devices.
PMID- 25852312
TI - The enhanced anticoagulation for graphene induced by COOH(+) ion implantation.
AB - Graphene may have attractive properties for some biomedical applications, but its
potential adverse biological effects, in particular, possible modulation when it
comes in contact with blood, require further investigation. Little is known about
the influence of exposure to COOH(+)-implanted graphene (COOH(+)/graphene)
interacting with red blood cells and platelets. In this paper, COOH(+)/graphene
was prepared by modified Hummers' method and implanted by COOH(+) ions. The
structure and surface chemical and physical properties of COOH(+)/graphene were
characterized by scanning electron microscopy (SEM), X-ray photoelectron
spectroscopy (XPS), and contact angle measurement. Systematic evaluation of
anticoagulation, including in vitro platelet adhesion assays and hemolytic
assays, proved that COOH(+)/graphene has significant anticoagulation. In
addition, at the dose of 5 * 10(17) ions/cm(2), COOH(+)/graphene responded best
on platelet adhesion, aggregation, and platelet activation.
PMID- 25852313
TI - Reduction of breakdown threshold by metal nanoparticle seeding in a DC
microdischarge.
AB - Significant reduction of the breakdown threshold in a DC microdischarge via
seeding metal nanoparticles has been demonstrated. Compared to standard Paschen
curves in dry air, reductions in the breakdown voltage of 5% to 25% were obtained
for PD values (the product of pressure and electrode gap distance) ranging from
20 to 40 Torr-cm by seeding aluminum and iron nanoparticles with mean sizes of 75
nm and 80 nm, respectively. No secondary energy source was required to achieve
this breakdown threshold reduction. From high-speed chemiluminescence imaging of
the discharge evolution, breakdown was shown to be initiated at reduced voltages.
Following breakdown, the increase in temperature ignited some of the
nanoparticles near the cathode. Results suggest that possible charging of the
nanoparticles within the gap may reduce the effective transient distance, leading
to the threshold reduction.
PMID- 25852314
TI - NH3-treated WO3 as low-cost and efficient counter electrode for dye-sensitized
solar cells.
AB - A novel low-cost and efficient counter electrode (CE) was obtained by treating
catalytic inert tungsten trioxide (WO3) nanomaterial in NH3 atmosphere at
elevated temperatures. The formation of tungsten oxynitride from WO3 after NH3
treatment, as evidenced by X-ray photoelectron spectroscopy and X-ray
diffraction, increases the catalytic activity of the CE. Correspondingly, the
power conversion efficiency (PCE) of the DSC is significantly increased from 0.9%
for pristine WO3 CE to 5.9% for NH3-treated WO3 CE. The photovoltaic performance
of DSC using NH3-treated WO3 CE is comparable to that of DSC using standard Pt CE
(with a PCE of 6.0%). In addition, it is also shown that NH3 treatment is more
efficient than H2 or N2 treatment in enhancing the catalytic performance of WO3
CE. This work highlights the potential of NH3-treated WO3 for the application in
DSCs and provides a facile method to get highly efficient and low-cost CEs from
catalytic inert metal oxides.
PMID- 25852315
TI - Nanosphere-in-a-nanoegg: damping the high-order modes induced by symmetry
breaking.
AB - We study the optical properties of the nanosphere-in-a-nanoegg structure (NSNE)
by the three-dimensional finite difference time domain method. We demonstrate the
suppression of the high-order plasmon modes in NSNE, which is induced by the
plasmon interaction between the inner nanosphere and the outer nanoegg shell. A
two-layer plasmon hybridization model is presented to explain this mechanism. The
results we showed for plasmon mode suppression would be important to the design
of the metal plasmonic devices. In addition, due to high tunable plasmon
resonances in the near-infrared region (700 to 1,300 nm) with sub-100-nm size,
NSNE can serve as a good substitute for the Au-silica-Au multilayer nanoshells in
biological applications. Furthermore, compared with the Au-silica-Au nanoshells,
NSNE has the advantage that the strong field enhancement can be achieved at the
outer surface of the Au shell.
PMID- 25852316
TI - Real-time detection of chlorine gas using Ni/Si shell/core nanowires.
AB - We demonstrate the selective adsorption of Ni/Si shell/core nanowires (Ni-Si NWs)
with a Ni outer shell and a Si inner core on molecularly patterned substrates and
their application to sensors for the detection of chlorine gas, a toxic halogen
gas. The molecularly patterned substrates consisted of polar SiO2 regions and
nonpolar regions of self-assembled monolayers of octadecyltrichlorosilane (OTS).
The NWs showed selective adsorption on the polar SiO2 regions, avoiding assembly
on the nonpolar OTS regions. Utilizing these assembled Ni-Si NWs, we demonstrate
a sensor for the detection of chlorine gas. The utilization of Ni-Si NWs resulted
in a much larger sensor response of approximately 23% to 5 ppm of chlorine gas
compared to bare Ni NWs, due to the increased surface-to-volume ratio of the Ni
Si shell/core structure. We expect that our sensor will be utilized in the future
for the real-time detection of halogen gases including chlorine with high
sensitivity and fast response.
PMID- 25852317
TI - In situ growth of ZnO nanoparticles in precursor-insensitive water-in-oil
microemulsion as soft nanoreactors.
AB - Zinc oxide (ZnO) nanostructures of uniform shapes and sizes (spherical, needle
like, and acicular) were directly synthesized using a relatively precursor
insensitive water-in-n-heptane microemulsion system stabilized by a mixture of
cationic and non-ionic surfactants. With this colloidal system, the synthesized
ZnO possesses the highest reported surface area (76 m(2) g(-1)) among the
published reports utilizing other microemulsion systems. Such precursor
insensitivity allowed studying the effect of Zn precursor:precipitating agent
molar ratio (as high as 1:8) on the particle size, specific surface area,
porosity, and morphology of the synthesized nanoparticles. The interaction of the
cationic surfactant head groups and their Br(-) counter ions with Zn(2+) and OH(
) ions is believed to play a major role in controlling the ZnO characteristics.
Due to such interactions, it is believed that the nucleation processes are
retarded while the growth is more dominating if compared with other microemulsion
systems.
PMID- 25852318
TI - Effect of grain size on thermal transport in post-annealed antimony telluride
thin films.
AB - The effects of grain size and strain on the temperature-dependent thermal
transport of antimony telluride (Sb2Te3) thin films, controlled using post
annealing temperatures of 200 degrees C to 350 degrees C, were investigated using
the 3-omega method. The measured total thermal conductivities of 400-nm-thick
thin films annealed at temperatures of 200 degrees C, 250 degrees C, 300 degrees
C, 320 degrees C, and 350 degrees C were determined to be 2.0 to 3.7 W/m . K in
the 20 to 300 K temperature range. We found that the film grain size, rather than
the strain, had the most prominent effect on the reduction of the total thermal
conductivity. To confirm the effect of grain size on temperature-dependent
thermal transport in the thin films, the experimental results were analyzed using
a modified Callaway model approach.
PMID- 25852319
TI - Electrical transport properties of an isolated CdS microrope composed of twisted
nanowires.
AB - CdS is one of the important II-VI group semiconductors. In this paper, the
electrical transport behavior of an individual CdS microrope composed of twisted
nanowires is studied. It is found that the current-voltage (I-V) characteristics
show two distinct power law regions from 360 down to 60 K. Space-charge-limited
current (SCLC) theory is used to explain these temperature- and electric-field
dependent I-V curves. The I-V data can be well fitted by this theory above 100 K,
and the corresponding carrier mobility, trap energy, and trap concentration are
also obtained. However, the I-V data exhibit some features of the Coulomb
blockade effect below 80 K.
PMID- 25852320
TI - Axially connected nanowire core-shell p-n junctions: a composite structure for
high-efficiency solar cells.
AB - A composite nanostructure for high-efficiency solar cells that axially connects
nanowire core-shell p-n junctions is proposed. By axially connecting the p-n
junctions in one nanowire, the solar spectrum is separated and absorbed in the
top and bottom cells with respect to the wavelength. The unique structure of
nanowire p-n junctions enables substantial light absorption along the nanowire
and efficient radial carrier separation and collection. A coupled three
dimensional optoelectronic simulation is used to evaluate the performance of the
structure. With an excellent current matching, a promising efficiency of 19.9%
can be achieved at a low filling ratio of 0.283 (the density of the nanowire
array), which is much higher than the tandem axial p-n junctions.
PMID- 25852321
TI - Mechanical properties of carbyne: experiment and simulations.
AB - The results of the high-field technique for obtaining and testing the carbyne
strength in situ are presented. By using molecular dynamics simulation and ab
initio calculations, a comprehensive analysis of the results is executed. High
field technique for experimental measurement of the carbyne strength in situ is
briefly described. It is shown that the technique used gives a lower estimation
for strength of carbyne, which equals 251 GPa at T = 77 K. This value is close to
the strength 7.85 nN (250 GPa) of contact atomic bond between carbyne and
graphene sheet, from which the monatomic chain is pulled. The strength of carbyne
itself is determined by strength of an edge atomic bond and it is ~ 12.35 nN (393
GPa) at T = 0 K. For carbynes containing more than 10 to 12 atoms, the
coefficient of elasticity (k Y = 145.40 nN) and the elastic modulus (Y = 4631
GPa) are ascertain.
PMID- 25852322
TI - Inductive crystallization effect of atomic-layer-deposited Hf0.5Zr0.5O2 films for
ferroelectric application.
AB - Ferroelectric Hf x Zr1-x O2 thin films are considered promising candidates for
future lead-free CMOS-compatible ferroelectric memory application. The inductive
crystallization behaviors and the ferroelectric performance of Hf0.5Zr0.5O2 thin
films prepared by atomic layer deposition were investigated. Inductive
crystallization can be induced by the film growth condition and appropriate top
electrode selection. In this work, a Ni/Hf0.5Zr0.5O2/Ru/Si stack annealed at 550
degrees C for 30 s in N2 ambient after the Ni top electrode has been deposited
was manufactured, and it shows the best ferroelectric hysteresis loop in the
dielectric thickness of 25 nm, with a remanent polarization value of 6 MUC/cm(2)
and a coercive field strength of 2.4 MV/cm measured at 10 kHz. Endurance,
retention, and domain switching current characteristics were evaluated well for
potential application in the field of ferroelectric field effect transistor
(FeFET) and nonvolatile ferroelectric memories (FeRAM).
PMID- 25852323
TI - Investigation of monolithic passively mode-locked quantum dot lasers with
extremely low repetition frequency.
AB - The dynamical regimes and performance optimization of quantum dot monolithic
passively mode-locked lasers with extremely low repetition rate are investigated
using the numerical method. A modified multisection delayed differential equation
model is proposed to accomplish simulations of both two-section and three-section
passively mode-locked lasers with long cavity. According to the numerical
simulations, it is shown that fundamental and harmonic mode-locking regimes can
be multistable over a wide current range. These dynamic regimes are studied, and
the reasons for their existence are explained. In addition, we demonstrate that
fundamental pulses with higher peak power can be achieved when the laser is
designed to work in a region with smaller differential gain.
PMID- 25852324
TI - Studies on the mechanical stretchability of transparent conductive film based on
graphene-metal nanowire structures.
AB - Transparent electrodes with superior flexibility and stretchability as well as
good electrical and optical properties are required for applications in wearable
electronics with comfort designs and high performances. Here, we present hybrid
nanostructures as stretchable and transparent electrodes based on graphene and
networks of metal nanowires, and investigate their optical, electrical, and
mechanical properties. High electrical and optical characteristics, superb
bendability (folded in half), excellent stretchability (10,000 times in
stretching cycles with 100% in tensile strain toward a uniaxial direction and 30%
in tensile strain toward a multi-axial direction), strong robustness against
electrical breakdown and thermal oxidation were obtained through comprehensive
study. We believe that these results suggest a substantial promise application in
future electronics.
PMID- 25852325
TI - Human-like collagen protein-coated magnetic nanoparticles with high magnetic
hyperthermia performance and improved biocompatibility.
AB - Human-like collagen (HLC)-coated monodispersed superparamagnetic Fe3O4
nanoparticles have been successfully prepared to investigate its effect on heat
induction property and cell toxicity. After coating of HLC, the sample shows a
faster rate of temperature increase under an alternating magnetic field although
it has a reduced saturation magnetization. This is most probably a result of the
effective heat conduction and good colloid stability due to the high charge of
HLC on the surface. In addition, compared with Fe3O4 nanoparticles before coating
with HLC, HLC-coated Fe3O4 nanoparticles do not induce notable cytotoxic effect
at higher concentration which indicates that HLC-coated Fe3O4 nanoparticles has
improved biocompatibility. Our results clearly show that Fe3O4 nanoparticles
after coating with HLC not only possess effective heat induction for cancer
treatment but also have improved biocompatibility for biomedicine applications.
PMID- 25852326
TI - Enhanced efficiency of inverted polymer solar cells by using solution-processed
TiOx/CsOx cathode buffer layer.
AB - In this work, a double-buffer film of TiOx coated with CsOx (TiOx/CsOx) was
solution prepared to be applied in poly(3-hexylthiophene):indene-C60 bisadduct
(P3HT:ICBA) and P3HT:[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) inverted
polymer solar cells (PSCs). Compared with TiOx films and CsOx films, the
TiOx/CsOx double-buffer film exhibited a favorable energy-level alignment among
TiOx, CsOx, and the electron acceptor of PCBM or ICBA a better surface
morphology; and an enhanced wetting and adhesion property with a contact angle of
21.0 degrees , leading to a higher electron mobility of 5.52 * 10(-3) cm(2) V(
1).s(-1). Moreover, the P3HT:ICBA and P3HT:PCBM photovoltaic devices with the
double-buffer film showed the best power conversion efficiency up to 5.65% and
3.76%, respectively. Our results not only present that the double-buffer film is
superior than the single film of TiOx and CsOx, but also imply that the solution
processed film has a potential to be generally used in roll-to-roll processed
organic photovoltaic devices.
PMID- 25852327
TI - Microstructure, optical properties, and catalytic performance of Cu2O-modified
ZnO nanorods prepared by electrodeposition.
AB - Cu2O-modified ZnO nanorods are prepared by a two-step electrodeposition method on
ITO substrates, and the deposition time of Cu2O is 0, 1, 5, and 10 min,
respectively. Cu2O particles are embedded in the interspaces of the ZnO nanorods,
and the amounts of the Cu2O particles increase obviously when the deposition time
lasts longer. The peaks corresponding to ZnO nanorods and Cu2O particles are
detected from scanning electron microscope (SEM) and X-ray diffraction (XRD)
results. UV-vis absorption spectra measurements have shown the bandgaps of ZnO
nanorods shift from 3.22 to 2.75 eV. The methyl orange (MO) concentration can be
reduced to around 15% in 100 min with Cu2O electrodeposition time for 10 min.
PMID- 25852328
TI - Strong localization effect and carrier relaxation dynamics in self-assembled
InGaN quantum dots emitting in the green.
AB - Strong localization effect in self-assembled InGaN quantum dots (QDs) grown by
metalorganic chemical vapor deposition has been evidenced by temperature
dependent photoluminescence (PL) at different excitation power. The integrated
emission intensity increases gradually in the range from 30 to 160 K and then
decreases with a further increase in temperature at high excitation intensity,
while this phenomenon disappeared at low excitation intensity. Under high
excitation, about 40% emission enhancement at 160 K compared to that at low
temperature, as well as a higher internal quantum efficiency (IQE) of 41.1%, was
observed. A strong localization model is proposed to describe the possible
processes of carrier transport, relaxation, and recombination. Using this model,
the evolution of excitation-power-dependent emission intensity, shift of peak
energy, and linewidth variation with elevating temperature is well explained.
Finally, two-component decays of time-resolved PL (TRPL) with various excitation
intensities are observed and analyzed with the biexponential model, which enables
us to further understand the carrier relaxation dynamics in the InGaN QDs.
PMID- 25852329
TI - Optical properties and bandgap evolution of ALD HfSiOx films.
AB - Hafnium silicate films with pure HfO2 and SiO2 samples as references were
fabricated by atomic layer deposition (ALD) in this work. The optical properties
of the films as a function of the film composition were measured by vacuum
ultraviolet (VUV) ellipsometer in the energy range of 0.6 to 8.5 eV, and they
were investigated systematically based on the Gaussian dispersion model.
Experimental results show that optical constants and bandgap of the hafnium
silicate films can be tuned by the film composition, and a nonlinear change
behavior of bandgap with SiO2 fraction was observed. This phenomenon mainly
originates from the intermixture of d-state electrons in HfO2 and Si-O
antibonding states in SiO2.
PMID- 25852330
TI - Influence of the local structure in phase-change materials on their dielectric
permittivity.
AB - Ge-Sb-Te alloys, which belong to the phase-change materials, are promising
materials for data storage and display and data visualization applications due to
their unique properties. This includes a remarkable difference of their
electrical and optical properties in the amorphous and crystalline state.
Pronounced change of optical properties for Ge-Sb-Te alloys is linked to the
different bonding types and different atomic arrangements in amorphous and
crystalline states. The dielectric function of phase-change materials has been
investigated in the far infrared (FIR) range. Phonons have been detected by FTIR
spectroscopy. Difference of the dispersion of the dielectric permittivity of
amorphous and crystalline samples is caused by different structures in different
states which contribute to the dielectric permittivity.
PMID- 25852331
TI - Preparation of silver colloids with improved uniformity and stable surface
enhanced Raman scattering.
AB - Silver colloids of uniform shape and size are prepared by a two-step reduction.
Small silver particles form initially by the rapid reduction of silver nitrate
with sodium citrate at 100 degrees C and then grow at 92 degrees C. The reaction
processes and resulting silver colloids are characterized by transmission
electron microscopy, ultraviolet-visible absorption spectrophotometry, zeta
potential measurements, and Ag(+) concentration analysis. The surface-enhanced
Raman scattering (SERS) activity of the silver colloids is then investigated,
using crystal violet (CV) as a SERS probe. The silver colloids exhibit uniform
shape and size and stable SERS activity. The average size of the silver particles
is 47 nm (14% relative standard deviation), while the average sizes of the silver
colloids prepared at 100 degrees C and 92 degrees C are 41 (30%) and 71 nm (33%),
respectively.
PMID- 25852333
TI - Fe-Al-C carbide phase nano-layer investigation as a substrate for epitaxial
diamond growth.
AB - Calculations of electron structure of supercells consisting of several layers of
ordinary stoichiometric K-phase and modified K-phase, on which according to our
assumptions epitaxial growth of diamonds is possible, were conducted. Stability
of calculated cells was considered, and optimal number of layers of the
stoichiometric K-phase in the supercell was determined in order for it to be
thermodynamically stable. Electronic structure of carbon in the modified K-phase
layer was considered and compared to electron structure of carbon in diamond.
PMID- 25852332
TI - Multidimensional effects of biologically synthesized silver nanoparticles in
Helicobacter pylori, Helicobacter felis, and human lung (L132) and lung carcinoma
A549 cells.
AB - Silver nanoparticles (AgNPs) are prominent group of nanomaterials and are
recognized for their diverse applications in various health sectors. This study
aimed to synthesize the AgNPs using the leaf extract of Artemisia princeps as a
bio-reductant. Furthermore, we evaluated the multidimensional effect of the
biologically synthesized AgNPs in Helicobacter pylori, Helicobacter felis, and
human lung (L132) and lung carcinoma (A549) cells. UV-visible (UV-vis)
spectroscopy confirmed the synthesis of AgNPs. X-ray diffraction (XRD) indicated
that the AgNPs are specifically indexed to a crystal structure. The results from
Fourier transform infrared spectroscopy (FTIR) indicate that biomolecules are
involved in the synthesis and stabilization of AgNPs. Dynamic light scattering
(DLS) studies showed the average size distribution of the particle between 10 and
40 nm, and transmission electron microscopy (TEM) confirmed that the AgNPs were
significantly well separated and spherical with an average size of 20 nm. AgNPs
caused dose-dependent decrease in cell viability and biofilm formation and
increase in reactive oxygen species (ROS) generation and DNA fragmentation in H.
pylori and H. felis. Furthermore, AgNPs induced mitochondrial-mediated apoptosis
in A549 cells; conversely, AgNPs had no significant effects on L132 cells. The
results from this study suggest that AgNPs could cause cell-specific apoptosis in
mammalian cells. Our findings demonstrate that this environmentally friendly
method for the synthesis of AgNPs and that the prepared AgNPs have
multidimensional effects such as anti-bacterial and anti-biofilm activity against
H. pylori and H. felis and also cytotoxic effects against human cancer cells.
This report describes comprehensively the effects of AgNPs on bacteria and
mammalian cells. We believe that biologically synthesized AgNPs will open a new
avenue towards various biotechnological and biomedical applications in the near
future.
PMID- 25852334
TI - Synthesis and detection the oxidization of Co cores of Co@SiO2 core-shell
nanoparticles by in situ XRD and EXAFS.
AB - In this paper, the Co@SiO2 core-shell nanoparticles were prepared by the sol-gel
method. The oxidization of Co core nanoparticles was studied by the synchrotron
radiation-based techniques including in situ X-ray diffraction (XRD) and X-ray
absorption fine structure (XAFS) up to 800 degrees C in air and N2 protection
conditions, respectively. It was found that the oxidization of Co cores is
undergoing three steps regardless of being in air or in N2 protection condition.
In the first step ranging from room temperature to 200 degrees C, the Co cores
were dominated by Co(0) state as well as small amount of Co(2+) ions. When
temperature was above 300 degrees C, the interface between Co cores and SiO2
shells was gradually oxidized into Co(2+), and the CoO layer was observed. As the
temperature increasing to 800 degrees C, the Co cores were oxidized to Co3O4 or
Co3O4/CoO. Nevertheless, the oxidization kinetics of Co cores is different for
the Co@SiO2 in air and N2 gas conditions. Generally, the O2 in the air could get
through the SiO2 shells easily onto the Co core surface and induce the
oxidization of the Co cores due to the mesoporous nature of the SiO2 shells.
However, in N2 gas condition, the O atoms can only be from the SiO2 shells, so
the diffusion effect of O atoms in the interface between Co core and SiO2 shell
plays a key role.
PMID- 25852335
TI - Hot plasmonic electrons for generation of enhanced photocurrent in gold-TiO2
nanocomposites.
AB - In this manuscript, for the first time, we report a combination of
electrophoretic and sintering approaches for introducing gold nanoparticles into
nanoporous TiO2 films to generate 'hot' electrons resulting in a strong
enhancement of photocurrent. The Au-TiO2 nanocomposite material was prepared by
the electrophoretic deposition of gold nanoparticles into a porous
nanoparticulate titanium dioxide film, creating a photoactive electrode. The
composite film demonstrates a significant increase in the short circuit current
(I sc) compared to unmodified TiO2 when excited at or close to the plasmon
resonance of the gold nanoparticles. Then, we employed a thermal ripening process
as a method of increasing the I sc of these electrodes and also as a method of
tuning the plasmon peak position, with a high degree of selectivity. Photo
electrochemical investigations revealed that the increase in photocurrent is
attributed to the generation and separation of plasmonically generated hot
electrons at the gold/TiO2 interface and also the inter-band generation of holes
in gold nanoparticles by photons with lambda < 520 nm. Theoretical modelling
outputs perfectly match our results obtained from photo-physical studies of the
processes leading to enhanced photocurrent.
PMID- 25852336
TI - Impact of program/erase operation on the performances of oxide-based resistive
switching memory.
AB - Further performance improvement is necessary for resistive random access memory
(RRAM) to realize its commercialization. In this work, a novel pulse operation
method is proposed to improve the performance of RRAM based on Ti/HfO2/Pt
structure. In the DC voltage sweep of the RRAM device, the SET transition is
abrupt under positive bias. If current sweep with positive bias is utilized in
SET process, the SET switching will become gradual, so SET is current controlled.
In the negative voltage sweep for RESET process, the change of current with
applied voltage is gradual, so RESET is voltage controlled. Current sweep SET and
voltage sweep RESET shows better controllability on the parameter variation.
Considering the SET/RESET characteristics in DC sweep, in the corresponding pulse
operation, the width and height of the pulse series can be adjusted to control
the SET and RESET process, respectively. Our new method is different from the
traditional pulse operation in which both the width and height of program/erase
pulse are simply kept constant which would lead to unnecessary damage to the
device. In our new method, in each program or erase operation, a series of pulses
with the width/height gradually increased are made use of to fully finish the
SET/RESET switching but no excessive stress is generated at the same time, so
width/height-controlled accurate SET/RESET can be achieved. Through the
operation, the uniformity and endurance of the RRAM device has been significantly
improved.
PMID- 25852337
TI - Performance evaluation of multi-junction solar cells by spatially resolved
electroluminescence microscopy.
AB - An electroluminescence microscopy combined with a spectroscopy was developed to
visually analyze multi-junction solar cells. Triple-junction solar cells with
different conversion efficiencies were characterized by using this system. The
results showed that the mechanical damages and material defects in solar cells
can be clearly distinguished, indicating a high-resolution imaging. The external
quantum efficiency (EQE) measurements demonstrated that different types of
defects or damages impacted cell performance in various degrees and the electric
leakage mostly degraded the EQE. Meanwhile, we analyzed the relationship between
electroluminescence intensity and short-circuit current density J SC. The results
indicated that the gray value of the electroluminescence image corresponding to
the intensity was almost proportional to J SC. This technology provides a
potential way to evaluate the current matching status of multi-junction solar
cells.
PMID- 25852338
TI - Morphology and electronic structure of nanoscale powders of calcium
hydroxyapatite.
AB - Atomic force microscopy, infrared spectroscopy and NMR studied morphological and
physicochemical properties of calcium hydroxyapatite powders produced by changing
the temperature parameters of synthesis. Features of morphology formation of
calcium hydroxyapatite nanoparticles with an annealing temperature within 200
degrees C to 1,100 degrees C were determined. It is shown that the particle size
of the apatite obtained that annealed 700 degrees C is 40 nm corresponding to the
particle size of apatite in native bone. The effect of dimension factor on
structural parameters of calcium hydroxyapatite is manifested in a more local
symmetry of the PO4 (3-) tetrahedra at nanodispersed calcium hydroxyapatite.
PMID- 25852339
TI - Synthesis of copper micro-rods with layered nano-structure by thermal
decomposition of the coordination complex Cu(BTA)2.
AB - Porous metallic copper was successfully prepared by a simple thermal
decomposition strategy. A coordination compound of Cu(BTA)2 with the morphology
of micro-rod crystal was synthesized as the precursor. The precursor to copper
transformation was performed and annealed at 600 degrees C with the shape
preserved. The copper micro-rods are assembled from unique thin lamellar layers,
each with the thickness of approximately 200 nm and nano-pores of approximately
20 to 100 nm. This morphology is highly related to the crystal structure of the
precursor. The mechanism of the morphology formation is proposed, which would be
able to offer a guideline toward porous metals with controllable macro/micro/nano
structures by the precursor crystal growth and design.
PMID- 25852340
TI - Folic-acid-conjugated pullulan/poly(DL-lactide-co-glycolide) graft copolymer
nanoparticles for folate-receptor-mediated drug delivery.
AB - BACKGROUND: Nanoparticles have been extensively investigated for targeted
delivery of anticancer drugs. Since the folate receptor is universally over
expressed on the tumor cell membrane, folic acid is often used to modify the fate
of nanoparticles in biologicals. METHODS: To fabricate targetable nanoparticles,
folic acid was conjugated to a pullulan backbone and poly(DL-lactide-co
glycolide) (PLGA) (abbreviated as FAPuLG) was conjugated. KB cells and NIH3T3
cell-bearing mice were prepared to prove folate receptor targeting of FAPuLG
nanoparticles. RESULTS AND DISCUSSION: Nanoparticles of FAPuLG copolymer that
self-assembled in water were small with diameters <200 nm. Doxorubicin (DOX) as a
model drug was incorporated into the FAPuLG nanoparticles that were used to treat
folate receptor over-expressing KB human carcinoma cells. Fluorescence microscopy
revealed that DOX-incorporated FAPuLG nanoparticles induced strong red
fluorescence in the KB cells in the absence of folic acid. However, fluorescence
intensity was decreased by blocking folate receptors. Antitumor activity of
FAPuLG nanoparticles against KB cells in vitro was also decreased by blocking
folate receptors. In animal study using near-infrared dye-conjugated FAPuLG
nanoparticles, fluorescence intensity was significantly higher at KB solid tumor
than that of NIH3T3. CONCLUSIONS: The results indicate that FAPuLG nanoparticles
can target the folate receptor of tumor cells. FAPuLG nanoparticles are a
promising candidate for active targeting of anticancer agents.
PMID- 25852341
TI - Atomic layer deposition for fabrication of HfO2/Al2O3 thin films with high laser
induced damage thresholds.
AB - Previous research on the laser damage resistance of thin films deposited by
atomic layer deposition (ALD) is rare. In this work, the ALD process for thin
film generation was investigated using different process parameters such as
various precursor types and pulse duration. The laser-induced damage threshold
(LIDT) was measured as a key property for thin films used as laser system
components. Reasons for film damaged were also investigated. The LIDTs for thin
films deposited by improved process parameters reached a higher level than
previously measured. Specifically, the LIDT of the Al2O3 thin film reached 40
J/cm(2). The LIDT of the HfO2/Al2O3 anti-reflector film reached 18 J/cm(2), the
highest value reported for ALD single and anti-reflect films. In addition, it was
shown that the LIDT could be improved by further altering the process parameters.
All results show that ALD is an effective film deposition technique for
fabrication of thin film components for high-power laser systems.
PMID- 25852342
TI - Polarized Raman spectroscopy with differing angles of laser incidence on single
layer graphene.
AB - Chemical vapor deposition (CVD)-grown single-layer graphene samples, transferred
onto a transmission electron microscope (TEM) grid and onto a quartz plate, were
studied using polarized Raman spectroscopy with differing angles of laser
incidence (theta). Two different polarization configurations are used. In an in
plane configuration, the polarization direction of both incident and scattered
light is parallel to the graphene plane. In an out-of-plane configuration, the
angle between the polarization vector and the graphene plane is the same as the
angle of laser incidence (theta). The normalized Raman intensity of the G-band
measured in the out-of-plane configuration, with respect to that in the in-plane
configuration, was analyzed as a function of theta. The normalized Raman
intensity showed approximately cos(2) theta-dependence up to theta = 70 degrees ,
which can be explained by the fact that only the electric field component of the
incident and the scattered photon in the out-of-plane configuration projected
onto the graphene plane can contribute to the Raman scattering process because of
the perfect confinement of the electrons to the graphene plane.
PMID- 25852343
TI - The impact of thickness and thermal annealing on refractive index for aluminum
oxide thin films deposited by atomic layer deposition.
AB - The aluminum oxide (Al2O3) thin films with various thicknesses under 50 nm were
deposited by atomic layer deposition (ALD) on silicon substrate. The surface
topography investigated by atomic force microscopy (AFM) revealed that the
samples were smooth and crack-free. The ellipsometric spectra of Al2O3 thin films
were measured and analyzed before and after annealing in nitrogen condition in
the wavelength range from 250 to 1,000 nm, respectively. The refractive index of
Al2O3 thin films was described by Cauchy model and the ellipsometric spectra data
were fitted to a five-medium model consisting of Si substrate/SiO2 layer/Al2O3
layer/surface roughness/air ambient structure. It is found that the refractive
index of Al2O3 thin films decrease with increasing film thickness and the
changing trend revised after annealing. The phenomenon is believed to arise from
the mechanical stress in ALD-Al2O3 thin films. A thickness transition is also
found by transmission electron microscopy (TEM) and SE after 900 degrees C
annealing.
PMID- 25852344
TI - Magnetic and electric properties of stoichiometric BiMnO3 thin films.
AB - It has been suggested that BiMnO3 is a material exhibiting both ferromagnetism
and ferroelectricity. Stoichiometry is rather easily achieved in a
polycrystalline sample, and ferromagnetic properties have been well documented
for bulk samples. Stoichiometry in thin films has been difficult to obtain, and
many physical properties have exhibit wide distributions mainly due to the
stoichiometry problem. Thin film studies on BiMnO3 have not shown clear evidence
of ferroelectricity, while other physical properties measured for the BiMnO3
films showed wide spectra, which has been attributed to cation and/or oxygen
vacancies. We fabricated BiMnO3 thin films with good stoichiometry and with
ferromagnetic properties comparable to those reported for stoichiometric BiMnO3:
Tc ~ 105 K and M sat ~ 3.6 MUB/Mn. The charge-electric field (Q-E) curve measured
at 5 K was fairly linear and free from hysteresis and showed no ferroelectric
order. This finding is consistent with the centrosymmetric crystal structure
recently suggested by theoretical calculations and structural studies on ceramic
samples of stoichiometric BiMnO3.
PMID- 25852345
TI - Quality and high yield synthesis of Ag nanowires by microwave-assisted
hydrothermal method.
AB - Silver nanowires (Ag-NWs) were obtained using microwave-assisted hydrothermal
method (MAH). The main advantage of the method is its high NWs production which
is greater than 90%. It is also easy, fast, and highly reproducible process. One
of the drawbacks presented so far in the synthesis of nanostructures by polyol
path is the high temperature used in the process, which is superior than the
boiling point of solvent (ethylene glycol), and also its excessive reaction time.
Here, Ag-NWs with diameters of 70 to 110 nm were synthesized in 5 min in large
quantities. Results showed that dimensions and shape of nanowires were very
susceptible to changes with reaction parameters. The reactor power and reactor
fill capacity were important for the synthesis. It was found that the reaction
time needs to be decreased because of the NWs which start to deform and break up
due to significant increase in the pressure's system. Energy-dispersive X-ray
spectroscopy and electron diffraction analysis (SAED) did not show corresponding
phases of AgO. Some aspects about synthesis parameters which are related to the
percent yield and size of nanowires are also discussed.
PMID- 25852346
TI - 'Cold' crystallization in nanostructurized 80GeSe2-20Ga2Se3 glass.
AB - 'Cold' crystallization in 80GeSe2-20Ga2Se3 chalcogenide glass nanostructurized
due to thermal annealing at 380 degrees C for 10, 25, 50, 80, and 100 h are
probed with X-ray diffraction, atomic force, and scanning electron microscopy, as
well as positron annihilation spectroscopy performed in positron annihilation
lifetime and Doppler broadening of annihilation line modes. It is shown that
changes in defect-related component in the fit of experimental positron lifetime
spectra for nanocrystallized glasses testify in favor of structural fragmentation
of larger free-volume entities into smaller ones. Nanocrystallites of Ga2Se3
and/or GeGa4Se8 phases and prevalent GeSe2 phase extracted mainly at the surface
of thermally treated samples with preceding nucleation and void agglomeration in
the initial stage of annealing are characteristic features of cold
crystallization.
PMID- 25852347
TI - Single-crystalline chromium silicide nanowires and their physical properties.
AB - In this work, chromium disilicide nanowires were synthesized by chemical vapor
deposition (CVD) processes on Si (100) substrates with hydrous chromium chloride
(CrCl3 . 6H2O) as precursors. Processing parameters, including the temperature of
Si (100) substrates and precursors, the gas flow rate, the heating time, and the
different flow gas of reactions were varied and studied; additionally, the
physical properties of the chromium disilicide nanowires were measured. It was
found that single-crystal CrSi2 nanowires with a unique morphology were grown at
700 degrees C, while single-crystal Cr5Si3 nanowires were grown at 750 degrees C
in reducing gas atmosphere. The crystal structure and growth direction were
identified, and the growth mechanism was proposed as well. This study with
magnetism, photoluminescence, and field emission measurements demonstrates that
CrSi2 nanowires are attractive choices for future applications in magnetic
storage, photovoltaic, and field emitters.
PMID- 25852348
TI - High-resolution X-ray diffraction analysis of strain distribution in GaN
nanowires on Si(111) substrate.
AB - In this work, the influence of micro- and macro-deformation profiles in GaN
nanowires (NWs) on the angular intensity distribution of X-ray diffraction are
studied theoretically. The calculations are performed by using kinematical theory
of X-ray diffraction and assuming the deformation decays exponentially from the
NW/substrate interface. Theoretical modeling of X-ray scattering from NWs with
different deformation profiles are carried out. We show that the shape of the
(002) 2theta/omega X-ray diffraction profile (XDP) is defined by initial
deformation at the NW's bottom and its relaxation depth given by the decay depth
of the exponential deformation profile. Also, we demonstrate that macro
deformation leads to XDP shift, whereas micro-deformations are the cause of XDP's
asymmetry and its symmetrical broadening. A good correlation between calculated
and experimental XDP from self-assembled GaN NWs on Si(111) substrate was
achieved by taking into account all parameters of micro- and macro-deformation
profiles.
PMID- 25852349
TI - Vanadia supported on nickel manganese oxide nanocatalysts for the catalytic
oxidation of aromatic alcohols.
AB - Vanadia nanoparticles supported on nickel manganese mixed oxides were synthesized
by co-precipitation method. The catalytic properties of these materials were
investigated for the oxidation of benzyl alcohol using molecular oxygen as
oxidant. It was observed that the calcination temperature and the size of
particles play an important role in the catalytic process. The catalyst was
evaluated for its oxidation property against aliphatic and aromatic alcohols,
which was found to display selectivity towards aromatic alcohols. The samples
were characterized by employing scanning electron microscopy, transmission
electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller analysis,
thermogravimetric analysis, and X-ray photoelectron spectroscopy.
PMID- 25852350
TI - Metal phthalocyanine: fullerene composite nanotubes via templating method for
enhanced properties.
AB - The use of templating method to synthesize the vanadyl 2,9,16,23-tetraphenoxy
29H,31H-phthalocyanine (VOPcPhO):[6,6]-phenyl C71 butyric acid methyl ester
(PC71BM) composite nanotubes is presented here. VOPcPhO is a p-type material and
PC71BM is an n-type material which acts as an electron donor and electron
acceptor, respectively. Both materials have been studied due to their potential
applications as solar energy converter and organic electronics. High-resolution
transmission electron microscope (HRTEM) and field emission scanning electron
microscope (FESEM) images have shown the replication of the porous template
diameter of approximately 200 nm with a superior incorporation of both VOPcPhO
and PC71BM. VOPcPhO:PC71BM composite nanotubes showed the significant properties
improvement if compared over their bulk heterojunction counterpart. UV-vis
spectra of composite nanotubes show a shift to a longer wavelength at the
absorption peaks. Significant quenching has been attained by the
photoluminescence spectra of VOPcPhO:PC71BM composite nanotubes which supports
the redshift of UV-vis absorption spectra. Presumably, the photo-induced charge
transfer and charge carrier dissociation can be enhanced from the VOPcPhO:PC71BM
composite nanotubes rather than the bulk heterojunction.
PMID- 25852351
TI - Enhanced photoelectrochemical and photocatalytic activity of WO3-surface modified
TiO2 thin film.
AB - Development of nanostructured photocatalysts for harnessing solar energy in
energy-efficient and environmentally benign way remains an important area of
research. Pure and WO3-surface modified thin films of TiO2 were prepared by
magnetron sputtering on indium tin oxide glass, and photoelectrochemical and
photocatalytic activities of these films were studied. TiO2 particles were <50
nm, while deposited WO3 particles were <20 nm in size. An enhancement in the
photocurrent was observed when the TiO2 surface was modified WO3 nanoparticles.
Effect of potential, WO3 amount, and radiations of different wavelengths on the
photoelectrochemical activity of TiO2 electrodes was investigated. Photocatalytic
activity of TiO2 and WO3-modified TiO2 for the decolorization of methyl orange
was tested. Graphical abstractWO3-surface modified TiO2 film showing better
photocatalytic and photoelectrocatalytic activity.
PMID- 25852352
TI - Controllable size-selective method to prepare graphene quantum dots from graphene
oxide.
AB - We demonstrated one-step method to fabricate two different sizes of graphene
quantum dots (GQDs) through chemical cutting from graphene oxide (GO), which had
many advantages in terms of simple process, low cost, and large scale in
manufacturing with higher production yield comparing to the reported methods.
Several analytical methods were employed to characterize the composition and
morphology of the resultants. Bright blue luminescent GQDs were obtained with a
produced yield as high as 34.8%. Moreover, how the different sizes affect
fluorescence wavelength mechanism was investigated in details.
PMID- 25852353
TI - Surface properties and biocompatibility of nanostructured TiO2 film deposited by
RF magnetron sputtering.
AB - Nanostructured TiO2 films are deposited on a silicon substrate using 150-W power
from the RF magnetron sputtering at working pressures of 3 to 5 Pa, with no
substrate bias, and at 3 Pa with a substrate bias of -50 V. X-ray diffraction
(XRD) analysis reveals that TiO2 films deposited on unbiased as well as biased
substrates are all amorphous. Surface properties such as surface roughness and
wettability of TiO2 films, grown in a plasma environment, under biased and
unbiased substrate conditions are reported according to the said parameters of RF
power and the working pressures. Primary rat osteoblasts (MC3T3-E1) cells have
been cultured on nanostructured TiO2 films fabricated at different conditions of
substrate bias and working pressures. The effects of roughness and hydrophilicity
of nanostructured TiO2 films on cell density and cell spreading have been
discussed.
PMID- 25852355
TI - Lithium ionic conduction and relaxation dynamics of spark plasma sintered
Li5La3Ta2O12 garnet nanoceramics.
AB - In the present work, nanoceramics of Li5La3Ta2O12 (LLT) lithium ion conductors
with the garnet-like structure are fabricated by spark plasma sintering (SPS)
technique at different temperatures of 850 degrees C, 875 degrees C, and 900
degrees C (SPS-850, SPS-875, and SPS-900). The grain size of the SPS nanoceramics
is in the 50 to 100 nm range, indicating minimal grain growth during the SPS
experiments. The ionic conduction and relaxation properties of the current
garnets are studied by impedance spectroscopy (IS) measurements. The SPS-875
garnets exhibit the highest total Li ionic conductivity of 1.25 * 10(-6) S/cm at
RT, which is in the same range as the LLT garnets prepared by conventional
sintering technique. The high conductivity of SPS-875 sample is due to the
enhanced mobility of Li ions by one order of magnitude compared to SPS-850 and
SPS-900 ceramics. The concentration of mobile Li(+) ions, n c, and their mobility
are estimated from the analysis of the conductivity spectra at different
temperatures. n c is found to be independent of temperature for the SPS
nanoceramics, which implies that the conduction process is controlled by the
Li(+) mobility. Interestingly, we found that only a small fraction of lithium
ions of 3.9% out of the total lithium content are mobile and contribute to the
conduction process. Moreover, the relaxation dynamics in the investigated
materials have been studied through the electric modulus formalism.
PMID- 25852354
TI - Chances and limitations of nanosized titanium dioxide practical application in
view of its physicochemical properties.
AB - Nanotechnology is a field of science that is nowadays developing in a dynamic
way. It seems to offer almost endless opportunities of contribution to many areas
of economy and human activity, in general. Thanks to nanotechnology, the so
called nanomaterials can be designed. They present structurally altered
materials, with their physical, chemical and biological properties entirely
differing from properties of the same materials manufactured in microtechnology.
Nanotechnology creates a unique opportunity to modify the matter at the level of
atoms and particles. Therefore, it has become possible to obtain items displaying
new, useful properties, i.e. self-disinfecting and self-cleaning surfaces. Those
surfaces are usually covered by a thin layer of a photocatalyst. The role of the
photocatalyst is most of the time performed by the nanosized titanium dioxide
(nano-TiO2). Excitation of nano-TiO2 by ultraviolet radiation initiates advanced
oxidation processes and reactions leading to the creation of oxygen vacancies
that bind water particles. As a result, photocatalytic surfaces are given new
properties. Those properties can then be applied in a variety of disciplines,
such as medicine, food hygiene, environmental protection or building industry.
Practically, the applications include inactivation of microorganisms, degradation
of toxins, removing pollutants from buildings and manufacturing of fog-free
windows or mirrors.
PMID- 25852356
TI - Nano- and microsized zeolites as a perspective material for potentiometric
biosensors creation.
AB - A number of potentiometric biosensors based on coimmobilization of enzymes with
different types of zeolite on pH-ion-sensitive field-effect transistor (ISFET)
have been developed. Their working characteristics have been determined and
compared. It was shown that clinoptilolite and zeolite Beta polymorph A (BEA) are
more promising for creating biosensors than zeolite A. Changing the concentration
of zeolite BEA in membranes, it is possible to extend the biosensor linear
measurement range. The two-layer method of deposition of the enzyme with
clinoptilolite was found to provide a significant increase in the biosensor
sensitivity to substrates, whereas thermal modification of the zeolite BEA
crystals can improve analytical characteristics of potentiometric biosensors for
detection of toxic substances. These results show that it is possible to regulate
the ISFET characteristics for different enzyme-based biosensors by tailoring the
electrode surfaces via different zeolites. This makes zeolites strong candidates
for integration into biosensors as ISFET modifiers.
PMID- 25852357
TI - Catalytic activities of noble metal atoms on WO3 (001): nitric oxide adsorption.
AB - Using first-principles density functional theory calculations within the
generalized gradient approximation, we investigate the adsorption of NO molecule
on a clean WO3(001) surface as well as on the noble metal atom (Cu, Ag, and Au)
deposited WO3(001) surfaces. We find that on a clean WO3 (001) surface, the NO
molecule binds to the W atom with an adsorption energy (E ads) of -0.48 eV. On
the Cu- and Ag-deposited WO3(001) surface where such noble metal atoms prefer to
adsorb on the hollow site, the NO molecule also binds to the W atom with E ads =
1.69 and -1.41 eV, respectively. This relatively stronger bonding of NO to the W
atom is found to be associated with the larger charge transfer of 0.43 e (Cu) and
0.33 e (Ag) from the surface to adsorbed NO. However, unlike the cases of Cu
WO3(001) and Ag-WO3(001), Au atoms prefer to adsorb on the top of W atom. On such
an Au-WO3(001) complex, the NO molecule is found to form a bond to the Au atom
with E ads = -1.32 eV. Because of a large electronegativity of Au atom, the
adsorbed NO molecule captures the less electrons (0.04 e) from the surface
compared to the Cu and Ag catalysts. Our findings not only provide useful
information about the NO adsorption on a clean WO3(001) surface as well as on the
noble metal atoms deposited WO3(001) surfaces but also shed light on a higher
sensitive WO3 sensor for NO detection employing noble metal catalysts.
PMID- 25852358
TI - Investigation of LRS dependence on the retention of HRS in CBRAM.
AB - The insufficient retention prevents the resistive random access memory from
intended application, such as code storage, FPGA, encryption, and others. The
retention characteristics of high resistance state (HRS) switching from different
low resistance state (LRS) were investigated in a 1-kb array with one transistor
and one resistor configuration. The HRS degradation was found strongly dependent
on the LRS: the lower the resistance of the LRS (R LRS) is, the worse HRS
retention will be. According to the quantum point contact model, the HRS
corresponds to a tiny tunnel gap or neck bridge with atomic size in the filament.
The degradation of HRS is due to the filling or widening of the neck point by the
diffusion of copper species from the residual filament. As the residual filament
is stronger in case of the lower R LRS, the active area around the neck point for
copper species diffusion is larger, resulting in higher diffusion probability and
faster degradation of HRS during the temperature-accelerated retention
measurement.
PMID- 25852359
TI - Influence of post-annealing on the off current of MoS2 field-effect transistors.
AB - Two-dimensional materials have recently been spotlighted, due to their unique
properties in comparison with conventional bulk and thin-film materials. Among
those materials, MoS2 is one of the promising candidates for the active layer of
electronic devices because it shows high electron mobility and pristine band gap.
In this paper, we focus on the evolution of the electrical property of the MoS2
field-effect transistor (FET) as a function of post-annealing temperature. The
results indicate that the off current drastically decreased at 200 degrees C and
increased at 400 degrees C while other factors, such as the mobility and
threshold voltage, show little variation. We consider that the decreasing off
current comes from the rearrangement of the MoS2 film and the elimination of the
surface residue. Then, the increasing off current was caused by the change of the
material's composition and adsorption of H2O and O2.
PMID- 25852360
TI - Conical islands of TiO2 nanotube arrays in the photoelectrode of dye-sensitized
solar cells.
AB - Ti conical island structures were fabricated using photolithography and the
reactive ion etching method. The resulting conical island structures were
anodized in ethylene glycol solution containing 0.25 wt% NH4F and 2 vol% H2O, and
conical islands composed of TiO2 nanotubes were successfully formed on the Ti
foils. The conical islands composed of TiO2 nanotubes were employed in
photoelectrodes for dye-sensitized solar cells (DSCs). DSC photoelectrodes based
on planar Ti structures covered with TiO2 nanotubes were also fabricated as a
reference. The short-circuit current (J sc) and efficiency of DSCs based on the
conical island structures were higher than those of the reference samples. The
efficiency of DSCs based on the conical island structures reached up to 1.866%.
From electrochemical impedance spectroscopy and open-circuit voltage (V oc) decay
measurements, DSCs based on the conical island structures exhibited a lower
charge transfer resistance at the counter cathode and a longer electron lifetime
at the interface of the photoelectrode and electrolyte compared to the reference
samples. The conical island structure was very effective at improving
performances of DSCs based on TiO2 nanotubes. Graphical AbstractConical islands
of TiO2 nanotube arrays are fabricated by an anodizing process with Ti protruding
dots which have a conical shape. The conical islands are applied for use in DSC
photoelectrodes. DSCs based on the conical islands of TiO2 nanotube arrays have
the potential to achieve higher efficiency levels compared to DSCs based on
normal TiO2 nanotubes and TiO2 nanoparticles because the conical islands of TiO2
nanotube arrays enlarge the surface area for dye adsorption.
PMID- 25852361
TI - Organic-inorganic materials containing nanoparticles of zirconium hydrophosphate
for baromembrane separation.
AB - Organic-inorganic membranes were obtained by stepwise modification of
poly(ethyleneterephthalate) track membrane with nanoparticles of zirconium
hydrophosphate. The modifier was inserted inside pores of the polymer, a size of
which is 0.33 MUm. Inner active layer was formed by this manner. Evolution of
morphology and functional properties of the membranes were investigated using
methods of porosimetry, potentiometry and electron microscopy. The nanoparticles
(4 to 10 nm) were found to form aggregates, which block pores of the polymer.
Pores between the aggregates (4 to 8 nm) as well as considerable surface charge
density provide significant transport numbers of counter ions (up to 0.86 for
Na(+)). The materials were applied to baromembrane separation of corn distillery.
It was found that precipitate is formed mainly inside the pores of the pristine
membrane. In the case of the organic-inorganic material, the deposition occurs
onto the outer surface and can be removed by mechanical way. Location of the
active layer inside membranes protects it against damage.
PMID- 25852362
TI - Thermochemically activated carbon as an electrode material for supercapacitors.
AB - The results of electrochemical studies of nanoporous carbon as electrode material
for electrochemical capacitors (EC) are presented in this work. Nanoporous carbon
material (NCM) was obtained from the raw materials of plant origin by
carbonization and subsequent activation in potassium hydroxide. It is established
that there is an optimal ratio of 1:1 between content of KOH and carbon material
at chemical activation, while the maximum specific capacity of NCM is 180 F/g. An
equivalent electrical circuit, which allows modeling of the impedance spectra in
the frequency range of 10(-2) to 10(5) Hz, is proposed, and a physical
interpretation of each element of the electrical circuit is presented.
PMID- 25852363
TI - Influence of semiconductor and metal nanoparticles on the dielectric properties
of ionic matrix cadmium octanoate.
AB - Dielectric properties of ionic composites consisted of cadmium octanoate matrix
and semiconductor or metal nanoparticles have been investigated. The
nanoparticles of different nature (semiconductor CdS, metal Au, and metal core
semiconductor shell Au-CdS) were chemically synthesized in the smectic A phase of
(Cd(+2)(C7H15COO)(-2), CdC8) that was used as a nanoreactor. These nanocomposites
are very stable and well ordered; the size and shape of the nanoparticles (NPs)
are well controlled during the synthesis. The main aim of the research was to
examine the influence of nanoparticles on the dielectric properties of ionic
matrix, which has smectic A ordered structure. Electrical characteristics were
investigated at different temperatures, which correspond to different phases of
the material. The conductivity of nanocomposites has an activation nature. The
electrical conductivity anisotropy confirms the structural anisotropy of the
nanocomposites. The conductivity of the nanocomposite along the cation-anion
layers is higher by 2 orders of magnitude than that across the cation-anion
layers. Basing on the experimental data, we proposed the simple model of the
charge carriage process.
PMID- 25852364
TI - Dynamics of mass transport during nanohole drilling by local droplet etching.
AB - Local droplet etching (LDE) utilizes metal droplets during molecular beam epitaxy
for the self-assembled drilling of nanoholes into III/V semiconductor surfaces.
An essential process during LDE is the removal of the deposited droplet material
from its initial position during post-growth annealing. This paper studies the
droplet material removal experimentally and discusses the results in terms of a
simple model. The first set of experiments demonstrates that the droplet material
is removed by detachment of atoms and spreading over the substrate surface.
Further experiments establish that droplet etching requires a small arsenic
background pressure to inhibit re-attachment of the detached atoms. Surfaces
processed under completely minimized As pressure show no hole formation but
instead a conservation of the initial droplets. Under consideration of these
results, a simple kinetic scaling model of the etching process is proposed that
quantitatively reproduces experimental data on the hole depth as a function of
the process temperature and deposited amount of droplet material. Furthermore,
the depth dependence of the hole side-facet angle is analyzed.
PMID- 25852365
TI - Biosensor for human IgE detection using shear-mode FBAR devices.
AB - Film bulk acoustic resonators (FBARs) have been evaluated for use as biosensors
because of their high sensitivity and small size. This study fabricated a novel
human IgE biosensor using shear-mode FBAR devices with c-axis 23 degrees -tilted
AlN thin films. Off-axis radio frequency (RF) magnetron sputtering method was
used for deposition of c-axis 23 degrees -tilted AlN thin films. The deposition
parameters were adopted as working pressure of 5 mTorr, substrate temperature of
300 degrees C, sputtering power of 250 W, and 50 mm distance between off-axis and
on-axis. The characteristics of the AlN thin films were investigated by X-ray
diffraction and scanning electron microscopy. The frequency response was measured
with an HP8720 network analyzer with a CASCADE probe station. The X-ray
diffraction revealed (002) preferred wurtzite structure, and the cross-sectional
image showed columnar structure with 23 degrees -tilted AlN thin films. In the
biosensor, an Au/Cr layer in the FBAR backside cavity was used as the detection
layer and the Au surface was modified using self-assembly monolayers (SAMs)
method. Then, the antigen and antibody were coated on biosensor through their
high specificity property. Finally, the shear-mode FBAR device with k t (2) of
3.18% was obtained, and the average sensitivity for human IgE detection of about
1.425 * 10(5) cm(2)/g was achieved.
PMID- 25852366
TI - High-performance HfO x /AlO y -based resistive switching memory cross-point array
fabricated by atomic layer deposition.
AB - Resistive switching memory cross-point arrays with TiN/HfO x /AlO y /Pt structure
were fabricated. The bi-layered resistive switching films of 5-nm HfO x and 3-nm
AlO y were deposited by atomic layer deposition (ALD). Excellent device
performances such as low switching voltage, large resistance ratio, good cycle-to
cycle and device-to-device uniformity, and high yield were demonstrated in the
fabricated 24 by 24 arrays. In addition, multi-level data storage capability and
robust reliability characteristics were also presented. The achievements
demonstrated the great potential of ALD-fabricated HfO x /AlO y bi-layers for the
application of next-generation nonvolatile memory.
PMID- 25852367
TI - Pure electron-electron dephasing in percolative aluminum ultrathin film grown by
molecular beam epitaxy.
AB - We have successfully grown ultrathin continuous aluminum film by molecular beam
epitaxy. This percolative aluminum film is single crystalline and strain free as
characterized by transmission electron microscopy and atomic force microscopy.
The weak anti-localization effect is observed in the temperature range of 1.4 to
10 K with this sample, and it reveals that, for the first time, the dephasing is
purely caused by electron-electron inelastic scattering in aluminum.
PMID- 25852368
TI - Metal nanoparticle-enhanced photocurrent in GaAs photovoltaic structures with
microtextured interfaces.
AB - The photocurrent enhancement effect caused by Au and Ag nanoparticles for GaAs
based photovoltaic structures of surface barrier or p-n junction type with
microtextured interfaces has been investigated in dependence on the conditions of
nanoparticles deposition and, respectively, on the shape and local dielectric
environment of obtained nanoparticle arrays. Three nanoparticle deposition
methods have been checked: 1) photoinduced chemical deposition of Au from aqueous
AuCl3 solution forming nanowires on the ridges of quasigrating-type surface
microrelief, 2) deposition of Ag nanoparticles from colloidal suspension on the
GaAs substrate covered with poly(vinylpyridine), and 3) drop and dry deposition
of Au/SiO2 core-shell nanoparticles from aqueous colloid solution. The
comprehensive investigation of optical reflectance, photoelectric, and electrical
characteristics of the fabricated barrier structures has shown the highest
photovoltaic parameters for surface microrelief of quasigrating-type and
electroless Au nanoparticle deposition. The analysis of characteristics obtained
allowed us also to define the mechanisms of the total photocurrent enhancement.
PMID- 25852369
TI - Influence of crystal structure of nanosized ZrO2 on photocatalytic degradation of
methyl orange.
AB - Nanosized ZrO2 powders with near pure monoclinic, tetragonal, and cubic
structures synthesized by various methods were used as catalysts for
photocatalytic degradation of methyl orange. The structural and textural
properties of the samples were analyzed by X-ray diffraction, Raman spectroscopy,
TEM, UV-vis, X-ray photoelectron spectroscopy (XPS), and N2 adsorption
measurements. The performance of synthesized ZrO2 nanoparticles in the
photocatalytic degradation of methyl orange under UV light irradiation was
evaluated. The photocatalytic activity of the pure monoclinic ZrO2 sample is
higher than that of the tetragonal and cubic ZrO2 samples under optimum identical
conditions. The characterization results revealed that monoclinic ZrO2
nanoparticles possessed high crystallinity and mesopores with diameter of 100 A.
The higher activity of the monoclinic ZrO2 sample for the photocatalytic
degradation of methyl orange can be attributed to the combining effects of
factors including the presence of small amount of oxygen-deficient zirconium
oxide phase, high crystallinity, large pores, and high density of surface
hydroxyl groups.
PMID- 25852370
TI - A facile approach to prepare silicon-based Pt-Ag tubular dendritic nano-forests
(tDNFs) for solar-light-enhanced methanol oxidation reaction.
AB - In this paper, a facile two-step Galvanic replacement reaction (GRR) is proposed
to prepare Pt-Ag tubular dendritic nano-forests (tDNFs) in ambient condition for
enhancing methanol oxidation reaction (MOR) under solar illumination. In the
first GRR, a homogeneous layer of silver dendritic nano-forests (DNFs) with 10
MUm in thickness was grown on Si wafer in 5 min in silver nitride (AgNO3) and
buffer oxide etchant (BOE) solution. In the second GRR, we utilized
chloroplatinic acid (H2PtCl6) as the precursor for platinum (Pt) deposition to
further transform the prepared Ag DNFs into Pt-Ag tDNFs. The catalytic
performance and solar response of the Pt-Ag tDNFs toward methanol electro
oxidation are also studied by cyclic voltammetry (CV) and chronoamperometry (CA).
The methanol oxidation current was boosted by 6.4% under solar illumination on
the Pt-Ag tDNFs due to the induced localized surface plasmon resonance (LSPR) on
the dendritic structure. Current results provide a cost-effective and facile
approach to prepare solar-driven metallic electrodes potentially applicable to
photo-electro-chemical fuel cells.
PMID- 25852371
TI - Effects of doping and annealing on properties of ZnO films grown by atomic layer
deposition.
AB - Undoped and Al-doped ZnO films were synthesized by atomic layer deposition at 150
degrees C and then annealed at 350 degrees C in different atmospheres. Effects of
doping and annealing on the film growth mode and properties were investigated.
The undoped film has strong UV emission and weak Zn interstitial emission.
Annealing introduces O vacancies, decreases Zn interstitials, and results in
weakening and blue-shifting of the UV emission which is sensitive to annealing
atmosphere. Al doping induces the film growing with its c-axis parallel to the
substrate surface. It also introduces non-radiative centers and weakens the UV
emission. Al doping widens the film bandgap, which has a quadratic dependence on
Al content. Al doping decreases the film resistivity to 5.3 * 10(-3) Omega . cm.
Annealing has little effect on photoluminescence of the doped films, but it
degrades undoped and doped ZnO film conductivity dramatically; and the
degradation depends on the annealing ambient.
PMID- 25852372
TI - Transparent and flexible capacitors based on nanolaminate Al2O3/TiO2/Al2O3.
AB - Transparent and flexible capacitors based on nanolaminate Al2O3/TiO2/Al2O3
dielectrics have been fabricated on indium tin oxide-coated polyethylene
naphthalate substrates by atomic layer deposition. A capacitance density of 7.8
fF/MUm(2) at 10 KHz was obtained, corresponding to a dielectric constant of 26.3.
Moreover, a low leakage current density of 3.9 * 10(-8) A/cm(2) at 1 V has been
realized. Bending test shows that the capacitors have better performances in
concave conditions than in convex conditions. The capacitors exhibit an average
optical transmittance of about 70% in visible range and thus open the door for
applications in transparent and flexible integrated circuits.
PMID- 25852373
TI - Positronics of subnanometer atomistic imperfections in solids as a high
informative structure characterization tool.
AB - Methodological possibilities of positron annihilation lifetime (PAL) spectroscopy
applied to characterize different types of nanomaterials treated within three
term fitting procedure are critically reconsidered. In contrast to conventional
three-term analysis based on admixed positron- and positronium-trapping modes,
the process of nanostructurization is considered as substitutional positron
positronium trapping within the same host matrix. Developed formalism allows
estimate interfacial void volumes responsible for positron trapping and
characteristic bulk positron lifetimes in nanoparticle-affected inhomogeneous
media. This algorithm was well justified at the example of thermally induced
nanostructurization occurring in 80GeSe2-20Ga2Se3 glass.
PMID- 25852374
TI - Local structure and paramagnetic properties of the nanostructured carbonaceous
material shungite.
AB - Using a scanning electron microscopy, elemental analysis, electron paramagnetic
resonance, and Raman scattering methods, two types of the shungite materials (Sh
II from Zazhogino deposit and shungite from a commercial filter (ShF)), with
different carbon content and porosity, are studied in this work. It was
established by scanning electron microscopy data that the structure of the
shungite samples is formed by a micron-size agglomeration of carbon and silicon
dioxide clusters. It is found from the Raman data that carbon fraction is formed
from sp(2)-hybridized clusters, size of which increases from 9 up to 12 nm after
annealing of the samples. High conductivity of shungite is found to belong to the
carbon nanoclusters of different sizes. Big clusters give the conduction electron
spin resonance signal with a Dysonian line shape with variable g-factor and line
width. The careful search of the nature of two other narrow electron paramagnetic
resonance signals in shungite, which used to be prescribed to fullerene-like
molecules, is fulfilled. Here, it is shown that the oxygen-deficient E'gamma
centers are responsible for these signals. A strong correlation is revealed
between the concentration of E'gamma centers and the line width of conduction
electron spin resonance signal, which occurs under annealing process of the
samples at T = 570 K. The correlation reasons are a spin-spin coupling between
two spin subsystems and time dependent of the E'gamma concentration during
annealing process.
PMID- 25852375
TI - Study of parasitic resistance effects in nanowire and nanoribbon biosensors.
AB - In this work, we investigate sensor design approaches for eliminating the effects
of parasitic resistance in nanowire and nanoribbon biosensors. Measurements of pH
with polysilicon nanoribbon biosensors are used to demonstrate a reduction in
sensitivity as the sensor length is reduced. The sensitivity (normalised
conductance change) is reduced from 11% to 5.5% for a pH change from 9 to 3 as
the sensing window length is reduced from 51 to 11 MUm. These results are
interpreted using a simple empirical model, which is also used to demonstrate how
the sensitivity degradation can be alleviated by a suitable choice of sensor
window length. Furthermore, a differential sensor design is proposed that
eliminates the detrimental effects of parasitic resistance. Measurements on the
differential sensor give a sensitivity of 15%, which is in good agreement with
the predicted maximum sensitivity obtained from modeling.
PMID- 25852376
TI - Nucleation and growth of primary nanostructures in SrTiO3 homoepitaxy.
AB - SrTiO3 nanoislands on SrTiO3 (001) in a diffusion-limited growth regime were
studied using in situ scanning tunneling microscopy (STM). The STM images
revealed two characteristic features of nucleation stages. First, the minimum
lateral size of the one-unit-cell (uc)-high SrTiO3 islands was 4 * 4 uc (2).
Second, one-dimensional SrTiO3 islands of a 4 uc width grew along the crystal
symmetry directions. These observations suggest that 4 * 4-uc (2) islands act as
a minimum nucleation seed, and the addition of SrTiO3 molecular species of the
same width is the primary and dominant growth process in SrTiO3 homoepitaxy. A
close inspection of the surface of the substrate during the deposition process
revealed possible connections between surface reconstruction and energetically
favorable nucleation of SrTiO3 islands.
PMID- 25852377
TI - Enhancement of polymer endurance to UV light by incorporation of semiconductor
nanoparticles.
AB - Improvement of polyvinyl alcohol stability against ultraviolet (UV) illumination
is achieved by introducing cadmium sulfide (CdS) nanoparticles into the polymeric
matrix. Enhancement of stability is analyzed by optical characterization methods.
UV protection is achieved by diminishing the probability of photo-activated
formation of defects in polymer. The sources of polymer protection are the
lowering of the efficiency of polymer excitation via partial absorption of
incident light by the embedded nanoparticles as well as the de-excitation of the
macromolecules that have already absorbed UV quanta via energy drain to
nanoparticles. Within the nanoparticles, the energy is either dissipated by
conversion to the thermal energy or reemitted as visible-range photoluminescence
quanta.
PMID- 25852378
TI - Composites of silica with immobilized cholinesterase incorporated into polymeric
shell.
AB - Synthetic approaches for new nanocomposite materials with relatively high
cholinesterase activity have been developed. The peculiarity of the formation of
such systems is the introduction of cholinesterase into polymer with subsequent
incorporation on the ready-made silica particles and into the polysiloxane
matrixes during sol-gel synthesis. Evaluation of the cholinesterase activity has
been fulfilled through the imitation of the acetylcholine chloride decomposition
reaction. Values of activity for cholinesterase nanocomposites demonstrated in
this work are higher than those for the native cholinesterase. The higher
activity of cholinesterase contained in nanocomposites was found for those
prepared using highly dispersed silica.
PMID- 25852379
TI - The nanostructuring of surfaces and films using interference lithography and
chalcogenide photoresist.
AB - The reversible and transient photostimulated structural changes in annealed
chalcogenide glass (ChG) layers were used to form interference periodic
structures on semiconductor surfaces and metal films. It was shown that negative
action etchants based on amines dissolve illuminated parts of a chalcogenide
film, i.e., act as positive etchants. The diffraction gratings and 2-D
interference structures on germanium ChGs - more environmentally acceptable
compounds than traditionally used arsenic chalcogenides - were recorded, and
their characteristics were studied.
PMID- 25852380
TI - Bimetallic core/shell nanoparticle-decorated 3D urchin-like hierarchical TiO2
nanostructures with magneto-responsive and decolorization characteristics.
AB - The semiconductors decorated with noble metals or magnetic metals have attracted
increasing attention due to multifunctional properties. In this article, we
prepare novel bimetallic core/shell nanoparticle (Co@Au and Co@Ag)-decorated 3D
urchin-like hierarchical TiO2 nanostructures through combining electroless
plating and in situ replacement processes. The morphology and structure are
characterized by scanning electron microscopy, transmission electron microscopy,
energy-dispersive spectroscopy, and a surface area analyzer. It demonstrates that
Co@Au and Co@Ag nanoparticles are uniformly decorated on urchin-like TiO2
nanostructures. The composite nanostructures show not only surface plasmon
absorption band from Au or Ag but also a magneto-responsive characteristic from
Co. This allows composite nanostructures to exhibit advantages including enhanced
decolorization efficiency compared to pure TiO2 nanostructures and facile
separation from a solution by magnetic field.
PMID- 25852381
TI - Fabrication and characterization of GaN-based light-emitting diodes without pre
activation of p-type GaN.
AB - We fabricated GaN-based light-emitting diodes (LEDs) without pre-activation of p
type GaN. During the fabrication process, a 100-nm-thick indium tin oxide film
was served as the p-type contact layer and annealed at 500 degrees C in N2
ambient for 20 min to increase its transparency as well as to activate the p-type
GaN. The electrical measurements showed that the LEDs were featured by a lower
forward voltage and higher wall-plug efficiency in comparison with LEDs using pre
activation of p-type GaN. We discussed the mechanism of activation of p-type GaN
at 500 degrees C in N2 ambient. Furthermore, x-ray photoemission spectroscopy
examinations were carried out to study the improved electrical performances of
the LEDs without pre-activation of p-type GaN.
PMID- 25852382
TI - The phase transformation of CuInS2 from chalcopyrite to wurtzite.
AB - In the present work, CuInS2 nanoparticles have been successfully synthesized by
water-bath method with deionized water as solvent and thioglycolic acid as
complexing agent at 80 degrees C. The phase transition of CuInS2 from
chalcopyrite to wurtzite was realized by adjusting the pH value of reaction
solution. The emergence of Cu2S in the condition of higher pH value of reaction
solution led to the formation of wurtzite CuInS2. This facile method that
controls the phase structure by adjusting the solution pH value could open a new
way to synthesize other I-III-VI2 ternary semiconductor compounds.
PMID- 25852383
TI - Synthesis and adsorption properties of chitosan-silica nanocomposite prepared by
sol-gel method.
AB - A hybrid nanocomposite material has been obtained by in situ formation of an
inorganic network in the presence of a preformed organic polymer. Chitosan
biopolymer and tetraethoxysilane (TEOS), which is the most common silica
precursor, were used for the sol-gel reaction. The obtained composite chitosan
silica material has been characterized by physicochemical methods such as
differential thermal analyses (DTA); carbon, hydrogen, and nitrogen (CHN)
elemental analysis; nitrogen adsorption/desorption isotherms, scanning electron
microscopy (SEM); and Fourier transform infrared (FTIR) spectroscopy to determine
possible interactions between silica and chitosan macromolecules. Adsorption of
microquantities of V(V), Mo(VI), and Cr(VI) oxoanions from the aqueous solutions
by the obtained composite has been studied in comparison with the chitosan beads,
previously crosslinked with glutaraldehyde. The adsorption capacity and kinetic
sorption characteristics of the composite material were estimated.
PMID- 25852384
TI - Investigations of ripple pattern formation on Germanium surfaces using 100-keV
Ar(+) ions.
AB - We have investigated the formation of nanoripples on the surface of germanium,
Ge(100), due to the effect of 100-keV Ar (+) ion irradiation. The irradiation was
carried out at different incidence angles from 0 degrees to 75 degrees in steps
of 15 degrees with respect to the surface normal with a fixed ion fluence of
approximately 3 * 10(17) ions/cm(2). Atomic force micrographs show an increase in
surface roughness from 0.5 to 4.3 nm for the pristine sample and the sample
irradiated at 60 degrees incidence angle due to cos(-1)(theta) dependence on
sputtering yield. With increase in angle of incidence, there is transition
observed from nanodots to aligned nanodots perpendicular to the direction of the
beam. There is an increase in size of the nanostructures observed from 44 to 103
nm with angle of incidence. The formation of nanoripples initiates at an angle of
theta ~ 45 degrees . Ripple pattern formation has taken place on the Ge surface
in the energy regime of 100 keV as compared to the other reports which had been
carried out using very low energy ions. Raman spectra reveal that the near
surface of crystalline Ge samples becomes amorphous due to interaction of Ar(+)
ions due to creation of defects through collision cascades.
PMID- 25852385
TI - Phase-change properties of GeSbTe thin films deposited by plasma-enchanced atomic
layer depositon.
AB - Phase-change access memory (PCM) appears to be the strongest candidate for next
generation high-density nonvolatile memory. The fabrication of ultrahigh-density
PCM depends heavily on the thin-film growth technique for the phase-changing
chalcogenide material. In this study, Ge2Sb2Te5 (GST) and GeSb8Te thin films were
deposited by plasma-enhanced atomic layer deposition (ALD) method using Ge
[(CH3)2 N]4, Sb [(CH3)2 N]3, Te(C4H9)2 as precursors and plasma-activated H2 gas
as reducing agent of the metallorganic precursors. Compared with GST-based
device, GeSb8Te-based device exhibits a faster switching speed and reduced reset
voltage, which is attributed to the growth-dominated crystallization mechanism of
the Sb-rich GeSb8Te films. These results show that ALD is an attractive method
for preparation of phase-change materials.
PMID- 25852386
TI - High-performance flexible Ag nanowire electrode with low-temperature atomic-layer
deposition fabrication of conductive-bridging ZnO film.
AB - As material for flexible transparent electrodes for organic photoelectric
devices, the silver nanowires (AgNWs) have been widely studied. In this work, we
propose a hybrid flexible anode with photopolymer substrate, which is composed of
spin-coating-processed AgNW meshes and of zinc oxide (ZnO) prepared by low
temperature (60 degrees C) atomic layer deposition. ZnO effectively fills in the
voids of the AgNW mesh electrode, which is thus able to contact to the device all
over the active area, to allow for efficient charge extraction/injection.
Furthermore, ZnO grown by low temperature mainly relies on hole conduction to
make the anode play a better role. Hole-only devices are fabricated to certify
the functionality of the low-temperature ZnO film. Finally, we confirm that the
ZnO film grown at a low temperature bring a significant contribution to the
performance of the modified AgNW anode.
PMID- 25852387
TI - The function of a 60-nm-thick AlN buffer layer in n-ZnO/AlN/p-Si(111).
AB - ZnO films were prepared on p-Si (111) substrates by using atomic layer
deposition. High-resolution x-ray diffraction (XRD), scanning electron microscopy
(SEM), x-ray photoelectron spectroscopy (XPS), photoluminescence (PL), and I-V
measurements were carried out to characterize structural, electrical, and optical
properties. After introducing a 60-nm-thick AlN buffer layer, the growth
direction of the ZnO films was changed from [10] to [0002]. Meanwhile, the ZnO
crystalline quality was significantly improved as verified by both XRD and PL
analyses. It has been demonstrated that the reverse leakage current was greatly
reduced with the AlN buffer layer. The valence band offsets have been determined
to be 3.06, 2.95, and 0.83 eV for ZnO/Si, ZnO/AlN, and AlN/Si heterojunctions,
respectively, and the band alignment of ZnO/Si heterojunction was modified to be
0.72 eV after introducing the AlN buffer layer. Our work offered a potential way
to fabricate Si-based ultraviolet light-emitting diodes and improve the device
performances.
PMID- 25852388
TI - Combination of inverted pyramidal nanovoid with silver nanoparticles to obtain
further enhancement and its detection for ricin.
AB - We have obtained the surface-enhanced Raman scattering substrate by depositing
silver nanoparticles on the surface of the inverted pyramidal nanovoid in order
to improve the enhance effects. Experimental results showed that the combined
substrate exhibited greater enhancement than the nanovoid substrate or
nanoparticles. In order to test the SERS activity of the combined substrates,
Rh6G and ricin toxin were used as Raman probes. Finite element method was
employed to simulate electric field and induced charge distribution of the
substrates, which have been used to explore the interaction between nanoparticles
and nanovoid as well as mechanism of the great enhancement.
PMID- 25852389
TI - Investigation on the passivated Si/Al2O3 interface fabricated by non-vacuum
spatial atomic layer deposition system.
AB - Currently, aluminum oxide stacked with silicon nitride (Al2O3/SiNx:H) is a
promising rear passivation material for high-efficiency P-type passivated emitter
and rear cell (PERC). It has been indicated that atomic layer deposition system
(ALD) is much more suitable to prepare high-quality Al2O3 films than plasma
enhanced chemical vapor deposition system and other process techniques. In this
study, an ultrafast, non-vacuum spatial ALD with the deposition rate of around 10
nm/min, developed by our group, is hired to deposit Al2O3 films. Upon post
annealing for the Al2O3 films, the unwanted delamination, regarded as blisters,
was found by an optical microscope. This may lead to a worse contact within the
Si/Al2O3 interface, deteriorating the passivation quality. Thin stoichiometric
silicon dioxide films prepared on the Si surface prior to Al2O3 fabrication
effectively reduce a considerable amount of blisters. The residual blisters can
be further out-gassed when the Al2O3 films are thinned to 8 nm and annealed above
650 degrees C. Eventually, the entire PERC with the improved triple-layer
SiO2/Al2O3/SiNx:H stacked passivation film has an obvious gain in open-circuit
voltage (V oc) and short-circuit current (J sc) because of the increased minority
carrier lifetime and internal rear-side reflectance, respectively. The electrical
performance of the optimized PERC with the V oc of 0.647 V, J sc of 38.2
mA/cm(2), fill factor of 0.776, and the efficiency of 19.18% can be achieved.
PMID- 25852390
TI - A new strategy for TiO2 whiskers mediated multi-mode cancer treatment.
AB - Traditional Chinese medicine (TCM) which functions as chemotherapeutic or
adjuvantly chemotherapeutic agents has been drawing a great many eyeballs for its
easy obtain and significant antitumor effects accompanied with less toxic and
side effects. PDT (photodynamic therapy) utilizes the fact that certain compounds
coined as photosensitizers, when exposed to light of a specific wavelength, are
capable of generating cytotoxic reactive oxygen species (ROS) such as hydroxyl
radical, hydrogen peroxide, and superoxide to kill cancer cells. Combinations of
cancer therapeutic modalities are studied to improve the efficacy of treatment.
This study aimed to explore a new strategy of coupling of titanium dioxide
whiskers (TiO2 Ws) with the anticancer drug gambogic acid (GA) in photodynamic
therapy. The nanocomposites were coined as GA-TiO2. The combination of TiO2 Ws
with GA induced a remarkable enhancement in antitumor activity estimated by MTT
assay, nuclear DAPI staining, and flow cytometry. Furthermore, the possible
signaling pathway was explored by reverse transcription polymerase chain reaction
(RT-PCR) and Western blot assay. These results identify TiO2 Ws of good
biocompatibility and photocatalytic activity. In human leukemia cells (K562
cells), TiO2 Ws could obviously increase the intracellular concentration of GA
and enhance its potential antitumor efficiency, suggesting that TiO2 Ws could act
as an efficient drug delivery carrier targeting GA to carcinoma cells. Moreover,
photodynamic GA-TiO2 nanocomposites could induce an evident reinforcement in
antitumor activity with UV illumination. These results reveal that such modality
combinations put forward a promising proposal in cancer therapy.
PMID- 25852391
TI - Structure and photoluminescence of the TiO2 films grown by atomic layer
deposition using tetrakis-dimethylamino titanium and ozone.
AB - TiO2 films were grown on silicon substrates by atomic layer deposition (ALD)
using tetrakis-dimethylamino titanium and ozone. Amorphous TiO2 film was
deposited at a low substrate temperature of 165 degrees C, and anatase TiO2 film
was grown at 250 degrees C. The amorphous TiO2 film crystallizes to anatase TiO2
phase with annealing temperature ranged from 300 degrees C to 1,100 degrees C in
N2 atmosphere, while the anatase TiO2 film transforms into rutile phase at a
temperature of 1,000 degrees C. Photoluminescence from anatase TiO2 films
contains a red band at 600 nm and a green band at around 515 nm. The red band
exhibits a strong correlation with defects of the under-coordinated Ti(3+) ions,
and the green band shows a close relationship with the oxygen vacancies on (101)
oriented anatase crystal surface. A blue shift of the photoluminescence spectra
reveals that the defects of under-coordinated Ti(3+) ions transform to surface
oxygen vacancies in the anatase TiO2 film annealing at temperature from 800
degrees C to 900 degrees C in N2 atmosphere.
PMID- 25852392
TI - Crystallographic orientation-dependent pattern replication in direct imprint of
aluminum nanostructures.
AB - In the present work, we perform molecular dynamics simulations corroborated by
experimental validations to elucidate the underlying deformation mechanisms of
single-crystalline aluminum under direct imprint using a rigid silicon master. We
investigate the influence of crystallographic orientation on the microscopic
deformation behavior of the substrate materials and its correlation with the
macroscopic pattern replications. Furthermore, the surface mechanical properties
of the patterned structures are qualitatively characterized by nanoindentation
tests. Our results reveal that dislocation slip and deformation twinning are two
primary plastic deformation modes of single-crystalline aluminum under the direct
imprint. However, both the competition between the individual deformation
mechanisms and the geometry between activated dislocation slip systems and
imprinted surface vary with surface orientation, which in turn leads to a strong
crystallographic orientation dependence of the pattern replications. It is found
that the (010) orientation leads to a better quality of pattern replication of
single-crystalline aluminum than the (111) orientation.
PMID- 25852393
TI - Angular shaping of fluorescence from synthetic opal-based photonic crystal.
AB - Spectral, angular, and temporal distributions of fluorescence as well as specular
reflection were investigated for silica-based artificial opals. Periodic
arrangement of nanosized silica globules in the opal causes a specific dip in the
defect-related fluorescence spectra and a peak in the reflectance spectrum. The
spectral position of the dip coincides with the photonic stop band. The latter is
dependent on the size of silica globules and the angle of observation. The
spectral shape and intensity of defect-related fluorescence can be controlled by
variation of detection angle. Fluorescence intensity increases up to two times at
the edges of the spectral dip. Partial photobleaching of fluorescence was
observed. Photonic origin of the observed effects is discussed.
PMID- 25852394
TI - The effect of silver nanoparticles (AgNPs) on proliferation and apoptosis of in
ovo cultured glioblastoma multiforme (GBM) cells.
AB - Recently, it has been shown that silver nanoparticles (AgNPs) provide a unique
approach to the treatment of tumors, especially those of neuroepithelial origin.
Thus, the aim of this study was to evaluate the impact of AgNPs on proliferation
and activation of the intrinsic apoptotic pathway of glioblastoma multiforme
(GBM) cells cultured in an in ovo model. Human GBM cells, line U-87, were placed
on chicken embryo chorioallantoic membrane. After 8 days, the tumors were divided
into three groups: control (non-treated), treated with colloidal AgNPs (40
MUg/ml), and placebo (tumors supplemented with vehicle only). At the end of the
experiment, all tumors were isolated. Assessment of cell proliferation and cell
apoptosis was estimated by histological, immunohistochemical, and Western blot
analyses. The results show that AgNPs can influence GBM growth. AgNPs inhibit
proliferation of GBM cells and seem to have proapoptotic properties. Although
there were statistically significant differences between control and AgNP groups
in the AI and the levels of active caspase 9 and active caspase 3, the level of
these proteins in GBM cells treated with AgNPs seems to be on the border between
the spontaneous apoptosis and the induced. Our results indicate that the
antiproliferative properties of silver nanoparticles overwhelm proapoptotic ones.
Further research focused on the cytotoxic effect of AgNPs on tumor and normal
cells should be conducted.
PMID- 25852395
TI - Au nanostructure arrays for plasmonic applications: annealed island films versus
nanoimprint lithography.
AB - This paper attempts to compare the main features of random and highly ordered
gold nanostructure arrays (NSA) prepared by thermally annealed island film and
nanoimprint lithography (NIL) techniques, respectively. Each substrate possesses
different morphology in terms of plasmonic enhancement. Both methods allow such
important features as spectral tuning of plasmon resonance position depending on
size and shape of nanostructures; however, the time and cost is quite different.
The respective comparison was performed experimentally and theoretically for a
number of samples with different geometrical parameters. Spectral characteristics
of fabricated NSA exhibited an expressed plasmon peak in the range from 576 to
809 nm for thermally annealed samples and from 606 to 783 nm for samples prepared
by NIL. Modelling of the optical response for nanostructures with typical shapes
associated with these techniques (parallelepiped for NIL and semi-ellipsoid for
annealed island films) was performed using finite-difference time-domain
calculations. Mathematical simulations have indicated the dependence of electric
field enhancement on the shape and size of the nanoparticles. As an important
point, the distribution of electric field at so-called 'hot spots' was
considered. Parallelepiped-shaped nanoparticles were shown to yield maximal
enhancement values by an order of magnitude greater than their semi-ellipsoid
shaped counterparts; however, both nanoparticle shapes have demonstrated
comparable effective electrical field enhancement values. Optimized Au
nanostructures with equivalent diameters ranging from 85 to 143 nm and height
equal to 35 nm were obtained for both techniques, resulting in the largest
electrical field enhancement. The application of island film thermal annealing
method for nanochips fabrication can be considered as a possible cost-effective
platform for various surface-enhanced spectroscopies; while the NIL-fabricated
NSA looks like more effective for sensing of small-size objects.
PMID- 25852396
TI - Room-temperature electrically pumped near-infrared random lasing from high
quality m-plane ZnO-based metal-insulator-semiconductor devices.
AB - Epitaxial m-plane ZnO thin films have been deposited on m-plane sapphire
substrates at a low temperature of 200 degrees C by atomic layer deposition. A 90
degrees in-plane rotation is observed between the m-plane ZnO thin films and the
sapphire substrates. Moreover, the residual strain along the ZnO [-12-10]
direction is released. To fabricate metal-insulator-semiconductor devices, a 50
nm Al2O3 thin film is deposited on the m-plane ZnO thin films. It is interesting
to observe the near-infrared random lasing from the metal-insulator-semiconductor
devices.
PMID- 25852397
TI - Photoinduced refractive index variation within picosecond laser pulses excitation
as the indicator of oxyorthosilicates single crystals composition modification.
AB - For the first time, the diagnostics of oxyorthosilicates single crystals based on
self-action of picosecond range laser pulses at 1,064 nm (1.17 eV) has been
performed. High sensitivity of the photoinduced refractive index variation to the
substitution of the Lu atoms by Gd in the LSO/LGSO crystalline host as well as to
the admixture of Ce was found. The effect can be explained with different
electron detrapping-recombination process efficiencies due to the resonant
electron excitation from the deep traps in the gap attributed to intrinsic oxygen
vacancies.
PMID- 25852398
TI - Enhanced performance of photonic crystal GaN light-emitting diodes with graphene
transparent electrodes.
AB - The two-dimensional (2D) triangle lattice air hole photonic crystal (PC) GaN
based light-emitting diodes (LED) with double-layer graphene transparent
electrodes (DGTE) have been produced. The current spreading effect of the double
layer graphene (GR) on the surface of the PC structure of the LED has been
researched. Specially, we found that the part of the graphene suspending over the
air hole of the PC structure was of much higher conductivity, which reduced the
average sheet resistance of the graphene transparent conducting electrode and
improved the current spreading of the PC LED. Therefore, the work voltage of the
DGTE-PC LED was obviously decreased, and the output power was greatly enhanced.
The COMSOL software was used to simulate the current density distribution of the
samples. The results show that the etching of PC structure results in the
degradation of the current spreading and that the graphene transparent conducting
electrode can offer an uniform current spreading in the DGTE-PC LED. PACS:
85.60.Jb; 68.65.Pq; 42.70.Qs.
PMID- 25852399
TI - Nitrogen-doped, FeNi alloy nanoparticle-decorated graphene as an efficient and
stable electrode for electrochemical supercapacitors in acid medium.
AB - Nitrogen-doped graphene decorated by iron-nickel alloy is introduced as a
promising electrode material for supercapacitors. Compared to pristine and Ni
decorated graphene, in acid media, the introduced electrode revealed excellent
specific capacitance as the corresponding specific capacitance was multiplied
around ten times with capacity retention maintained at 94.9% for 1,000 cycles.
Briefly, iron acetate, nickel acetate, urea, and graphene oxide were
ultrasonicated and subjected to MW heating and then sintered with melanin in Ar.
The introduced N-doped FeNi@Gr exhibits remarkable electrochemical behavior with
long-term stability.
PMID- 25852400
TI - Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa
nanocomposite.
AB - Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that
harbours drug between its two-layered sheets, forming a sandwich-like structure.
It is attracting a great deal of attention as an alternative drug delivery
(nanodelivery) system in the field of pharmacology due to their relative low
toxic potential. The production of these nanodelivery systems, aimed at improving
human health through decrease toxicity, targeted delivery of the active compound
to areas of interest with sustained release ability. In this study, we
administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium
nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity
following OECD guidelines. The oral administration of ZAL and ZA at a limit dose
of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14
days of the observation. The percentage of body weight gain of the animals showed
no significant difference between control and treatment groups. Animal from the
two treated groups gained weight continuously over the study period, which was
shown to be significantly higher than the weight at the beginning of the study (P
< 0.05). Biochemical analysis of animal serum showed no significant difference
between rats treated with ZAL, ZA and controls. There was no gross lesion or
histopathological changes observed in vital organs of the rats. The results
suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute
toxicity in the animals. Elemental analysis of tissues of treated animals
demonstrated the wider distribution of the nanocomposite including the brain. In
summary, findings of acute toxicity tests in this study suggest that zinc
aluminium nanocomposite intercalated with and the un-intercalated were safe when
administered orally in animal models for short periods of time. It also
highlighted the potential distribution ability of Tween-80 coated nanocomposite
after oral administration.
PMID- 25852401
TI - Ag nanoparticles-decorated ZnO nanorod array on a mechanical flexible substrate
with enhanced optical and antimicrobial properties.
AB - Heteronanostructured zinc oxide nanorod (ZnO NR) array are vertically grown on
polydimethylsiloxane (PDMS) through a hydrothermal method followed by an in situ
deposition of silver nanoparticles (Ag NPs) through a photoreduction process. The
Ag-ZnO heterostructured nanorods on PDMS are measured with an average diameter of
160 nm and an average length of 2 MUm. ZnO NRs measured by high-resolution
transmission electron microscope (HRTEM) shows highly crystalline with a lattice
fringe of 0.255 nm, which corresponds to the (0002) planes in ZnO crystal
lattice. The average diameter of the Ag NPs in situ deposited on the ZnO NRs is
estimated at 22 +/- 2 nm. As compared to the bare ZnO NRs, the heterostructured
Ag-ZnO nanorod array shows enhanced ultraviolet (UV) absorption at 440 nm, and
significant emission in the visible region (lambdaem = 542 nm). In addition, the
antimicrobial efficiency of Ag-ZnO heterostructured nanorod array shows obvious
improvement as compared to bare ZnO nanorod array. The cytotoxicity of ZnO
nanorod array with and without Ag NPs was studied by using 3 T3 mouse fibroblast
cell line. No significant toxic effect is imposed on the cells.
PMID- 25852402
TI - Anisotropic micro-cloths fabricated from DNA-stabilized carbon nanotubes: one
stop manufacturing with electrode needles.
AB - Among a variety of solution-based approaches to fabricate anisotropic films of
aligned carbon nanotubes (CNTs), we focus on the dielectrophoretic assembly
method using AC electric fields in DNA-stabilized CNT suspensions. We demonstrate
that a one-stop manufacturing system using electrode needles can draw anisotropic
DNA-CNT hybrid films of 10 to 100 um in size (i.e., free-standing DNA-CNT micro
cloths) from the remaining suspension into the atmosphere while maintaining
structural order. It has been found that a maximal degree of polarization (ca.
40%) can be achieved by micro-cloths fabricated from a variety of DNA-CNT
mixtures. Our results suggest that the one-stop method can impart
biocompatibility to the downsized CNT films and that the DNA-stabilized CNT micro
cloths directly connected to an electrode could be useful for biofuel cells in
terms of electron transfer and/or enzymatic activity.
PMID- 25852403
TI - Evolution of morphology and microstructure of GaAs/GaSb nanowire
heterostructures.
AB - In this paper, we successfully grow GaAs/GaSb core-shell heterostructure
nanowires (NWs) by molecular beam epitaxy (MBE). The as-grown GaSb shell layer
forms a wurtzite structure instead of the zinc blende structure that has been
commonly reported. Meanwhile, a bulgy GaSb nanoplate also appears on top of
GaAs/GaSb core-shell NWs and possesses a pure zinc blende phase. The growth mode
for core-shell morphology and underlying mechanism for crystal phase selection of
GaAs/GaSb nanowire heterostructures are discussed in detail.
PMID- 25852404
TI - AlGaN/GaN MISHEMTs with AlN gate dielectric grown by thermal ALD technique.
AB - Recently, AlN plasma-enhanced atomic layer deposition (ALD) passivation technique
had been proposed and investigated for suppressing the dynamic on-resistance
degradation behavior of high-electron-mobility transistors (HEMTs). In this
paper, a novel gate dielectric and passivation technique for GaN-on-Si AlGaN/GaN
metal-insulator-semiconductor high-electron-mobility transistors (MISHEMTs) is
presented. This technique features the AlN thin film grown by thermal ALD at 400
degrees C without plasma enhancement. A 10.6-nm AlN thin film was grown upon the
surface of the HEMT serving as the gate dielectric under the gate electrode and
as the passivation layer in the access region at the same time. The MISHEMTs with
thermal ALD AlN exhibit enhanced on/off ratio, reduced channel sheet resistance,
reduction of gate leakage by three orders of magnitude at a bias of 4 V, reduced
threshold voltage hysteresis of 60 mV, and suppressed current collapse
degradation.
PMID- 25852405
TI - Anatase TiO2 nanotube powder film with high crystallinity for enhanced
photocatalytic performance.
AB - We report on the synthesis of TiO2 nanotube (NT) powders using anodic oxidation
and ultrasonication. Compared to free-standing NT array films, the powder-type
NTs can be easily fabricated in a cost-effective way. Particularly, without the
substrate effect arising from underlying Ti metals, highly crystallized NT
powders with intact tube structures and pure anatase phase can be obtained using
high-temperature heat treatment. The application of NTs with different
crystallinity for the photocatalytic decomposition of methylene blue (MB) was
then demonstrated. The results showed that with increasing annealing temperature,
the photocatalytic decomposition rate was gradually enhanced, and the NT powder
electrode annealed at 650 degrees C showed the highest photoactivity. Compared to
typical NTs annealed at 450 degrees C, the rate constant increased by 2.7-fold,
although the surface area was 21% lower. These findings indicate that the better
photocatalytic activity was due to the significantly improved crystallinity of
anatase anodic NTs in powder form, resulting in a low density of crystalline
defects. This simple and efficient approach is applicable for scaled-up water
purification and other light utilization applications.
PMID- 25852406
TI - Investigation of GaInAs strain reducing layer combined with InAs quantum dots
embedded in Ga(In)As subcell of triple junction GaInP/Ga(In)As/Ge solar cell.
AB - The InAs/GaAs quantum dots structure embedded in GaInP/Ga(In)As/Ge triple
junction solar cell with and without Ga0.90In0.10As strain reducing layer was
investigated. Conversion efficiency of 33.91% at 1,000 suns AM 1.5D with
Ga0.90In0.10As strain reducing layer was demonstrated. A 1.19% improvement of the
conversion efficiency was obtained via inserting the Ga0.90In0.10As strain
reducing layer. The main contribution of this improvement was from the increase
of the short-circuit current, which is caused by the reduction of the Shockley
Read-Hall recombination centers. Consequently, there was a decrease in open
circuit voltage due to the lower thermal activation energy of confined carriers
in Ga0.9In0.1As than GaAs and a reduction in the effective band gap of quantum
dots.
PMID- 25852407
TI - Structure and properties of Co-doped ZnO films prepared by thermal oxidization
under a high magnetic field.
AB - The effect of a high magnetic field applied during oxidation on the structure,
optical transmittance, resistivity, and magnetism of cobalt (Co)-doped zinc oxide
(ZnO) thin films prepared by oxidizing evaporated Zn/Co bilayer thin films in
open air was studied. The relationship between the structure and properties of
films oxidized with and without an applied magnetic field was analyzed. The
results show that the high magnetic field obviously changed the structure and
properties of the Co-doped ZnO films. The Lorentz force of the high magnetic
field suppressed the oxidation growth on nanowhiskers. As a result, ZnO nanowires
were formed without a magnetic field, whereas polyhedral particles formed under a
6 T magnetic field. This morphology variation from dendrite to polyhedron caused
the transmittance below 1,200 nm of the film oxidized under a magnetic field of 6
T to be much lower than that of the film oxidized without a magnetic field. X-ray
photoemission spectroscopy indicated that the high magnetic field suppressed Co
substitution in the ZnO lattice, increased the concentration of oxygen vacancies,
and changed the chemical state of Co. The increased concentration of oxygen
vacancies affected the temperature dependence of the resistivity of the film
oxidized under a magnetic field of 6 T compared with that of the film oxidized
without a magnetic field. The changes of oxygen vacancy concentration and Co
state caused by the application of the high magnetic field also increase the
ferromagnetism of the film at room temperature. All of these results indicate
that a high magnetic field is an effective tool to modify the structure and
properties of ZnO thin films.
PMID- 25852408
TI - Thermal conductivity enhancement in thermal grease containing different CuO
structures.
AB - Different cupric oxide (CuO) structures have attracted intensive interest because
of their promising applications in various fields. In this study, three kinds of
CuO structures, namely, CuO microdisks, CuO nanoblocks, and CuO microspheres, are
synthesized by solution-based synthetic methods. The morphologies and crystal
structures of these CuO structures are characterized by field-emission scanning
electron microscope and X-ray diffractometer, respectively. They are used as
thermal conductive fillers to prepare silicone-based thermal greases, giving rise
to great enhancement in thermal conductivity. Compared with pure silicone base,
the thermal conductivities of thermal greases with CuO microdisks, CuO
nanoblocks, and CuO microspheres are 0.283, 0256, and 0.239 W/mK, respectively,
at filler loading of 9 vol.%, which increases 139%, 116%, and 99%, respectively.
These thermal greases present a slight descendent tendency in thermal
conductivity at elevated temperatures. These experimental data are compared with
Nan's model prediction, indicating that the shape factor has a great influence on
thermal conductivity improvement of thermal greases with different CuO
structures. Meanwhile, due to large aspect ratio of CuO microdisks, they can form
thermal networks more effectively than the other two structures, resulting in
higher thermal conductivity enhancement.
PMID- 25852409
TI - Structural and optical properties of position-retrievable low-density GaAs
droplet epitaxial quantum dots for application to single photon sources with
plasmonic optical coupling.
AB - The position of a single GaAs quantum dot (QD), which is optically active, grown
by low-density droplet epitaxy (DE) (approximately 4 QDs/MUm(2)), was directly
observed on the surface of a 45-nm-thick Al0.3Ga0.7As capping layer. The thin
thickness of AlGaAs capping layer is useful for single photon sources with
plasmonic optical coupling. A micro-photoluminescence for GaAs DE QDs has shown
exciton/biexciton behavior in the range of 1.654 to 1.657 eV. The direct
observation of positions of low-density GaAs DE QDs would be advantageous for
mass fabrication of devices that use a single QD, such as single photon sources.
PMID- 25852410
TI - A high-performance complementary inverter based on transition metal
dichalcogenide field-effect transistors.
AB - For several years, graphene has been the focus of much attention due to its
peculiar characteristics, and it is now considered to be a representative 2
dimensional (2D) material. Even though many research groups have studied on the
graphene, its intrinsic nature of a zero band-gap, limits its use in practical
applications, particularly in logic circuits. Recently, transition metal
dichalcogenides (TMDs), which are another type of 2D material, have drawn
attention due to the advantage of having a sizable band-gap and a high mobility.
Here, we report on the design of a complementary inverter, one of the most basic
logic elements, which is based on a MoS2 n-type transistor and a WSe2 p-type
transistor. The advantages provided by the complementary metal-oxide
semiconductor (CMOS) configuration and the high-performance TMD channels allow us
to fabricate a TMD complementary inverter that has a high-gain of 13.7. This work
demonstrates the operation of the MoS2 n-FET and WSe2 p-FET on the same
substrate, and the electrical performance of the CMOS inverter, which is based on
a different driving current, is also measured.
PMID- 25852411
TI - Microstructure inhomogeneity of Fe-31%Ni alloy and stabilization of austenite.
AB - Srystal structure and mechanism of crystallization of Fe-Ni alloys were studied
by methods of X-ray diffraction and metallography. It has been found that macro-
and microstructure of austenitic alloy was essentially heterogeneous at the
contact and free surfaces and in the volume of a ribbon. The indentified
peculiarities of the austenitic phase in different areas of the ribbon are
attributed to different cooling rates and the melt crystallization conditions.
PMID- 25852412
TI - Enhanced and tunable photoluminescence of polyphenylenevinylenes confined in
nanocomposite films.
AB - Conformation of macromolecules and interchain interactions determine spectral
properties of conjugated polymers (CP). An achievement of spatial confinement of
isolated chains is one of the routes to use this feature of CP for their
purposeful usage. In the present work, CP/O300 nanocomposites based on CP -
poly(p-phenylenevinylene) and poly(2-methoxy-5-(2'-ethylhexyloxy)-1,4
phenylenevinylene) - and silica nanoparticles (O300) are prepared. In comparison
with many previously known hybrid nanomaterials synthesized with the similar
purpose, CP/O300 nanocomposites are characterized by the essentially enhanced and
tunable photoluminescence. The greatest change of color coordinates is observed
for poly(p-phenylenevinylene)-based nanocomposites due to specific preparation
method and interaction with the inorganic component. The main emission from CP in
the CP/O300 nanocomposites is owing to 0-0 transitions, while 0-1 transitions,
associated with aggregate states of the CP chains, are suppressed.
PMID- 25852413
TI - Preparation of NiO two-dimensional grainy films and their high-performance gas
sensors for ammonia detection.
AB - Semiconductor NiO two-dimensional grainy films on glass substrates are shown to
be an ammonia-sensing devices with excellent comprehensive performance, such as
the good stability, short response time, outstanding recovery performance,
excellent sensitivity, and selectivity. The morphology and structure analysis of
gas sensing materials indicated that the as-fabricated NiO films was uniform and
highly ordered porous structure on substrates, which composed of small size
particles with diameters ranging from 8 to 30 nm. The shells of these particles
were ultrathin amorphous NiO plates, and the core of each particle was face
centered cubic single crystal structure. In the gas sensing performance tests, we
found that the excellent electron transport and interconnection properties of
sensing films improved the stability and recovery performance of sensors, and
porous surface structure increased the specific surface area of sensing films
leading to fast response and excellent sensitivity for sensors. Meanwhile, this
sensors owned outstanding selectivity toward ammonia which could be because NiO
sensing films had higher binding affinity for the electron-donating ammonia.
PMID- 25852414
TI - Primary structure of proteins as a nanowire for metabolic electronic transport.
AB - It is considered that the major process in an organism is the synthesis of the
adenosine triphosphate (ATP) molecules (its resumption from the adenosine
diphosphate (ADP) molecules). These molecules are the basic (if not unique)
energy resource of an organism. For the completion of process of the ATP
synthesis in mitochondria, it is necessary to transfer to it a pair of electrons
from places where electrons rise up as a result of oxidizing processes. Research
of mechanisms of such transfer is important therefore, in particular, from the
point of regulative influence on them in medical aims. Various proteins, the
primary structure of which can provide the transport of electrons between donors
and acceptors, saturate a volume and membranes of cages. A question about a
possibility to examine this primary structure of proteins as a nanowire of a
semiconductor nature is analyzed. The possibility of active transport of
electrons through its conductivity band is analyzed also. In this paper, it was
shown that a heterogeneous protein system is possible to be considered as a
semiconductor with an average-nitrogen nuclear subsystem and with an average
oxygen electronic subsystem. Also, it was shown that in the potential energy of
interaction between the electron and the nuclear subsystem indeed exists non
compensated contributions. These contributions are related to the radicals and
provide the active transport of electrons along the primary structure of protein
molecules. It was demonstrated also that external fields can have local
regulative influence on the transport of electron in proteins by compensating the
remaining field or strengthening it. Fulfilled analysis gives a possibility in
zero approximation of the application of representation of numbers of filling to
the protein molecule, considering it as the nanowire.
PMID- 25852416
TI - Nanoprocessing of layered crystalline materials by atomic force microscopy.
AB - By taking advantage of the mechanical anisotropy of crystalline materials,
processing at a single-layer level can be realized for layered crystalline
materials with periodically weak bonds. Mica (muscovite), graphite, molybdenum
disulfide (MoS2), and boron nitride have layered structures, and there is little
interaction between the cleavage planes existing in the basal planes of these
materials. Moreover, it is easy to image the atoms on the basal plane, where the
processed shape can be observed on the atomic level. This study reviews research
evaluating the nanometer-scale wear and friction as well as the nanometer-scale
mechanical processing of muscovite using atomic force microscopy (AFM). It also
summarizes recent AFM results obtained by our research group regarding the atomic
scale mechanical processing of layered materials including mica, graphite, MoS2,
and highly oriented pyrolytic graphite.
PMID- 25852415
TI - Synthesis of CuInS2 quantum dots using polyetheramine as solvent.
AB - This paper presents a facile solvothermal method of synthesizing copper indium
sulfide (CuInS2) quantum dots (QDs) via a non-coordinated system using
polyetheramine as a solvent. The structural and optical properties of the
resulting CuInS2 QDs were investigated using composition analysis, absorption
spectroscopy, and emission spectroscopy. We employed molar ratios of I, III, and
VI group elements to control the structure of CuInS2 QDs. An excess of group VI
elements facilitated precipitation, whereas an excess of group I elements
resulted in CuInS2 QDs with high photoluminescence quantum yield. The emission
wavelength and photoluminescence quantum yield could also be modulated by
controlling the composition ratio of Cu and In in the injection stock solution.
An increase in the portion of S shifted the emission wavelength of the QDs to a
shorter wavelength and increased the photoluminescence quantum yield. Our results
demonstrate that the band gap of the CuInS2 QDs is tunable with size as well as
the composition of the reactant. The photoluminescence quantum yield of the
CuInS2 QDs ranged between 0.7% and 8.8% at 250 degrees C. We also determined some
important physical parameters such as the band gaps and energy levels of this
system, which are crucial for the application of CuInS2 nanocrystals.
PMID- 25852417
TI - Intriguing photo-control of exchange bias in BiFeO3/La2/3Sr1/3MnO3 thin films on
SrTiO3 substrates.
AB - To date, electric fields have been widely used to control the magnetic properties
of BiFeO3-based antiferromagnet/ferromagnet heterostructures through application
of an exchange bias. To extend the applicability of exchange bias, however, an
alternative mechanism to electric fields is required. Here, we report the photo
control of exchange bias in BiFeO3/La2/3Sr1/3MnO3 thin films on an SrTiO3
substrate. Through an ex situ pulsed laser deposition technique, we successfully
synthesized epitaxial BiFeO3/La2/3Sr1/3MnO3 thin films on SrTiO3 substrates. By
measuring magnetoresistance under light illumination, we investigated the effect
of light illumination on resistance, exchange bias, and coercive field in
BiFeO3/La2/3Sr1/3MnO3 thin films. After illumination of red and blue lights, the
exchange bias was sharply reduced compared to that measured in the dark. With
increasing light intensity, the exchange bias under red and blue lights initially
decreased to zero and then appeared again. It is possible to reasonably explain
these behaviors by considering photo-injection from SrTiO3 and the photo
conductivity of La2/3Sr1/3MnO3. This study may provide a fundamental
understanding of the mechanism underlying photo-controlled exchange bias, which
is significant for the development of new functional spintronic devices.
PMID- 25852418
TI - First-principles calculations of perpendicular magnetic anisotropy in Fe1-x Co x
/MgO(001) thin films.
AB - The perpendicular magnetic anisotropy (PMA) of Fe1-x Co x thin films on MgO(001)
was investigated via first-principles density-functional calculations. Four
different configurations were considered based on their ground states: Fe/MgO,
Fe12Co4/MgO, Fe10Co6/MgO, and Fe8Co8/MgO. As the Co composition increases, the
amplitude of PMA increases first from Fe/MgO to Fe12Co4/MgO, and then decreases
in Fe10Co6/MgO; finally, the magnetic anisotropy becomes horizontal in
Fe8Co8/MgO. Analysis based on the second-order perturbation of the spin-orbit
interaction was carried out to illustrate the contributions from Fe and Co atoms
to PMA, and the differential charge density was calculated to give an intuitive
comparison of 3d orbital occupancy. The enhanced PMA in Fe12Co4/MgO is ascribed
to the optimized combination of occupied and unoccupied 3d states around the
Fermi energy from both interface Fe and Co atoms, while the weaker PMA in
Fe10Co6/MgO is mainly attributed to the modulation of the interface Co-d xy
orbital around the Fermi energy. By adjusting the Co composition in Fe1-x Co x ,
the density of states of transitional metal atoms will be modulated to optimize
PMA for future high-density memory application.
PMID- 25852419
TI - Direct patterning of gold nanoparticles using flexographic printing for
biosensing applications.
AB - In this paper, we have presented the use of flexographic printing techniques in
the selective patterning of gold nanoparticles (AuNPs) onto a substrate. Highly
uniform coverage of AuNPs was selectively patterned on the substrate surface,
which was subsequently used in the development of a glucose sensor. These AuNPs
provide a biocompatible site for the attachment of enzymes and offer high
sensitivity in the detection of glucose due to their large surface to volume
ratio. The average size of the printed AuNPs is less than 60 nm. Glucose sensing
tests were performed using printed carbon-AuNP electrodes functionalized with
glucose oxidase (GOx). The results showed a high sensitivity of 5.52 MUA mM(-1)
cm(-2) with a detection limit of 26 MUM. We have demonstrated the fabrication of
AuNP-based biosensors using flexographic printing, which is ideal for low-cost,
high-volume production of the devices.
PMID- 25852420
TI - Uniformity and passivation research of Al2O3 film on silicon substrate prepared
by plasma-enhanced atom layer deposition.
AB - Plasma-enhanced atom layer deposition (PEALD) can deposit denser films than those
prepared by thermal ALD. But the improvement on thickness uniformity and the
decrease of defect density of the films deposited by PEALD need further research.
A PEALD process from trimethyl-aluminum (TMA) and oxygen plasma was investigated
to study the influence of the conditions with different plasma powers and
deposition temperatures on uniformity and growth rate. The thickness and
refractive index of films were measured by ellipsometry, and the passivation
effect of alumina on n-type silicon before and after annealing was measured by
microwave photoconductivity decay method. Also, the effects of deposition
temperature and annealing temperature on effective minority carrier lifetime were
investigated. Capacitance-voltage and conductance-voltage measurements were used
to investigate the interface defect density of state (D it) of Al2O3/Si. Finally,
Al diffusion P(+) emitter on n-type silicon was passivated by PEALD Al2O3 films.
The conclusion is that the condition of lower substrate temperature accelerates
the growth of films and that the condition of lower plasma power controls the
films' uniformity. The annealing temperature is higher for samples prepared at
lower substrate temperature in order to get the better surface passivation
effects. Heavier doping concentration of Al increased passivation quality after
annealing by the effective minority carrier lifetime up to 100 MUs.
PMID- 25852421
TI - A flexible transparent gas barrier film employing the method of mixing ALD/MLD
grown Al2O3 and alucone layers.
AB - Atomic layer deposition (ALD) has been widely reported as a novel method for thin
film encapsulation (TFE) of organic light-emitting diodes and organic
photovoltaic cells. Both organic and inorganic thin films can be deposited by ALD
with a variety of precursors. In this work, the performances of Al2O3 thin films
and Al2O3/alucone hybrid films have been investigated. The samples with a 50 nm
Al2O3 inorganic layer deposited by ALD at a low temperature of 80 degrees C
showed higher surface roughness (0.503 +/- 0.011 nm), higher water vapor
transmission rate (WVTR) values (3.77 * 10(-4) g/m(2)/day), and lower
transmittance values (61%) when compared with the Al2O3 (inorganic)/alucone
(organic) hybrid structure under same conditions. Furthermore, a bending test
upon single Al2O3 layers showed an increased WVTR of 1.59 * 10(-3) g/m(2)/day.
However, the film with a 4 nm alucone organic layer inserted into the center
displayed improved surface roughness, barrier performance, and transmittance.
After the bending test, the hybrid film with 4 nm equally distributed alucone
maintained better surface roughness (0.339 +/- 0.014 nm) and barrier properties
(9.94 * 10(-5) g/m(2)/day). This interesting phenomenon reveals that multilayer
thin films consisting of inorganic layers and decentralized alucone organic
components have the potential to be useful in TFE applications on flexible
optical electronics.
PMID- 25852422
TI - A novel method to fabricate CoFe2O4/SrFe12O19 composite ferrite nanofibers with
enhanced exchange coupling effect.
AB - Nanocomposite of CoFe2O4/SrFe12O19 has been synthesized by the electrospinning
and calcination process. A novel method that cobalt powder was used to replace
traditional cobalt salt in the precursor sol-gel for electrospinning was
proposed. The crystal structures, morphologies, and magnetic properties of these
samples have been characterized in detail. Moreover, when the average crystallite
size of the hard/soft phases reached up to an optimal value, the CoFe2O4 have an
enhanced saturation magnetization of 62.8 emu/g and a coercivity of 2,290 Oe.
Significantly, the hysteresis loops for the nanocomposites show a single-phase
magnetization behavior, and it has been found that the exchange coupling
interaction strongly exists in the CoFe2O4/SrFe12O19 magnetic nanocomposite
nanofibers.
PMID- 25852423
TI - Hydrothermal-assisted exfoliation of Y/Tb/Eu ternary layered rare-earth
hydroxides into tens of micron-sized unilamellar nanosheets for highly oriented
and color-tunable nano-phosphor films.
AB - Efficient exfoliation of well-crystallized (Y0.96Tb x Eu0.04-x )2(OH)5NO3 . nH2O
(0 <= x <= 0.04) layered rare-earth hydroxide (LRH) crystals into tens of micron
sized unilamellar nanosheets has been successfully achieved by inserting water
insoluble oleate anions (C17H33COO(-)) into the interlayer of the LRH via
hydrothermal anion exchange at 120 degrees C, followed by delaminating in
toluene. The intercalation of oleate anions led to extremely expanded interlayer
distances (up to approximately 5.2 nm) of the LRH crystals and accordingly
disordered stacking of the ab planes along the c-axis and also weakened
interlayer interactions, without significantly damaging the ab plane. As a
consequence, the thickness of the LRH crystals increased from approximately 1 to
10 MUm, exhibiting a behavior similar to that observed from the smectite clay in
water. Highly [111]-oriented and approximately 100-nm thick oxide films of
(Y0.96Tb x Eu0.04-x ) 2O3 (0 <= x <= 0.04) have been obtained through spin
coating of the exfoliated colloidal nanosheets on quartz substrate, followed by
annealing at 800 degrees C. Upon UV excitation at 266 nm, the oxide transparent
films exhibit bright luminescence, with the color-tunable emission from red to
orange, yellow, and then green by increasing the Tb(3+) content from x = 0 to
0.04.
PMID- 25852424
TI - The synthesis of controlled shape nanoplasmonic silver-silica structures by
combining sol-gel technique and direct silver reduction.
AB - In this work, we have obtained nanoplasmonic silver structures deposited on the
glass substrates by combining sol-gel technology and direct silver ion reduction
on the film surfaces. The key point of the work was the usage of polyethylene
glycol 400 (PEG 400) both as the pore former and reducing agent for silver ions.
We have investigated the influence of PEG 400 amount on the formation of silver
nanoparticles on the film surface. It was found that control of PEG 400 amount in
the sols allows the creation of porous films with specific organized silver
nanoparticles or clusters on the surface. Optical, morphological and structural
characteristics of the structures were measured and studied. Atomic force
microscopy (AFM) and scanning electron microscopy (SEM) were used for
nanostructure size and shape characterization. We were able to form a 40- to 200
nm-diameter ring-type, spherical and self-assembled nanoparticles on the film
surface. The results of UV-vis absorbance spectra have shown the high quality of
plasmonic structures with plasmon resonance wavelength in the region between 470
and 480 nm. The synthesized silica films decorated with silver nanoparticles were
tested as substrates for the surface-enhanced Raman spectroscopy (SERS) and
showed an enhancement relative to micro-Raman of more than 200 times.
PMID- 25852425
TI - Protamine nanoparticles for improving shRNA-mediated anti-cancer effects.
AB - Protamine nanoparticles were designed by encapsulating small hairpin RNA (shRNA)
expressing plasmid DNA targeting the Bcl-2 gene (shBcl-2) to silence apoptosis
related Bcl-2 protein for improving the transfection efficiency and cytotoxicity
in cancer therapy. Our findings demonstrated that the obtained protamine
nanoparticles possessed excellent characterizations of small particle size,
homogenous distribution, positive charge, and high encapsulation efficiency of
gene. shBcl-2 loaded in nanoparticles (NPs) was protected effectively from the
degradation of DNase I and serum. More importantly, it significantly improved the
efficiency of transfection of shRNA in vitro in A549 cells and increased its
cytotoxicity and induced more cell apoptosis by silencing Bcl-2.
PMID- 25852426
TI - Excellent resistive switching properties of atomic layer-deposited
Al2O3/HfO2/Al2O3 trilayer structures for non-volatile memory applications.
AB - We have demonstrated a flexible resistive random access memory unit with trilayer
structure by atomic layer deposition (ALD). The device unit is composed of
Al2O3/HfO2/Al2O3-based functional stacks on TiN-coated Si substrate. The cross
sectional HRTEM image and XPS depth profile of Al2O3/HfO2/Al2O3 on TiN-coated Si
confirm the existence of interfacial layers between trilayer structures of
Al2O3/HfO2/Al2O3 after 600 degrees C post-annealing. The memory units of
Pt/Al2O3/HfO2/Al2O3/TiN/Si exhibit a typical bipolar, reliable, and reproducible
resistive switching behavior, such as stable resistance ratio (>10) of OFF/ON
states, sharp distribution of set and reset voltages, better switching endurance
up to 10(3) cycles, and longer data retention at 85 degrees C over 10 years. The
possible switching mechanism of trilayer structure of Al2O3/HfO2/Al2O3 has been
proposed. The trilayer structure device units of Al2O3/HfO2/Al2O3 on TiN-coated
Si prepared by ALD may be a potential candidate for oxide-based resistive random
access memory.
PMID- 25852427
TI - Soft magnetic properties of nanocrystalline Fe73B7Si16Nb3Cu1 alloy after rapid
heating under tensile stress.
AB - Amorphous Fe73B7Si16Nb3Cu1 ribbon was crystallized rapidly by electric current
heating under simultaneously applied tensile stress along the ribbon axis. As a
result, strong transverse magnetic anisotropy was induced in the ribbon. Dynamic
magnetic properties of the ribbons rapidly heated either under the tensile stress
or without tensile stress were measured using toroidal cores. Optimal electric
current heating regime that provides maximum improvement of the initial magnetic
permeability and core loss was determined. Tensile stress increase from 0 to 180
MPa was shown to result in the decrease of the initial magnetic permeability down
to 400 and core loss at frequencies from 0.4 to 200 kHz. Comparative analysis of
magnetic properties of the cut core (with non-magnetic gap) and the cores heated
under tensile stress was carried out. The magnetic properties of the latter cores
are advantageous for manufacturing the reactors and linear chokes of switch-mode
power supplies.
PMID- 25852428
TI - Oxidation precursor dependence of atomic layer deposited Al2O3 films in a
Si:H(i)/Al2O3 surface passivation stacks.
AB - In order to obtain a good passivation of a silicon surface, more and more stack
passivation schemes have been used in high-efficiency silicon solar cell
fabrication. In this work, we prepared a-Si:H(i)/Al2O3 stacks on KOH solution
polished n-type solar grade mono-silicon(100) wafers. For the Al2O3 film
deposition, both thermal atomic layer deposition (T-ALD) and plasma enhanced
atomic layer deposition (PE-ALD) were used. Interface trap density spectra were
obtained for Si passivation with a-Si films and a-Si:H(i)/Al2O3 stacks by a non
contact corona C-V technique. After the fabrication of a-Si:H(i)/Al2O3 stacks,
the minimum interface trap density was reduced from original 3 * 10(12) to 1 *
10(12) cm(-2) eV(-1), the surface total charge density increased by nearly one
order of magnitude for PE-ALD samples and about 0.4 * 10(12) cm(-2) for a T-ALD
sample, and the carrier lifetimes increased by a factor of three (from about 10
MUs to about 30 MUs). Combining these results with an X-ray photoelectron
spectroscopy analysis, we discussed the influence of an oxidation precursor for
ALD Al2O3 deposition on Al2O3 single layers and a-Si:H(i)/Al2O3 stack surface
passivation from field-effect passivation and chemical passivation perspectives.
In addition, the influence of the stack fabrication process on the a-Si film
structure was also discussed in this study.
PMID- 25852429
TI - Spray cooling characteristics of nanofluids for electronic power devices.
AB - The performance of a single spray for electronic power devices using deionized
(DI) water and pure silver (Ag) particles as well as multi-walled carbon nanotube
(MCNT) particles, respectively, is studied herein. The tests are performed with a
flat horizontal heated surface using a nozzle diameter of 0.5 mm with a definite
nozzle-to-target surface distance of 25 mm. The effects of nanoparticle volume
fraction and mass flow rate of the liquid on the surface heat flux, including
critical heat flux (CHF), are explored. Both steady state and transient data are
collected for the two-phase heat transfer coefficient, boiling curve/ cooling
history, and the corresponding CHF. The heat transfer removal rate can reach up
to 274 W/cm(2) with the corresponding CHF enhancement ratio of 2.4 for the
Ag/water nanofluids present at a volume fraction of 0.0075% with a low mass flux
of 11.9 * 10(-4) kg/cm(2)s.
PMID- 25852430
TI - Nanosized silver (II) pyridoxine complex to cause greater inflammatory response
and less cytotoxicity to RAW264.7 macrophage cells.
AB - With advancements in nanotechnology, silver has been engineered into a nanometre
size and has attracted great research interest for use in the treatment of
wounds. Silver nanoparticles (AgNPs) have emerged as a potential alternative to
conventional antibiotics because of their potential antimicrobial property.
However, AgNPs also induce cytotoxicity, generate reactive oxygen species (ROS),
and cause mitochondrial damage to human cells. Pyridoxine possesses antioxidant
and cell proliferation activity. Therefore, in the present investigation, a
nanosilver-pyridoxine complex (AgPyNP) was synthesized, and its cytotoxicity and
immune response was compared with AgNPs in macrophage RAW264.7 cells. Results
revealed that AgPyNPs showed less cytotoxicity compared with AgNPs by producing a
smaller amount of ROS in RAW264.7 cells. Surprisingly, however, AgPyNPs caused
macrophage RAW264.7 cells to secrete a larger amount of interleukin-8 (IL-8) and
generate a more active inflammatory response compared to AgNPs. It activated TNF
alpha, NF-kappaB p65, and NF-kappaB p50 to generate a more vigorous immune
protection that produces a greater amount of IL-8 compared to AgNPs. Overall
findings indicate that AgPyNPs exhibited less cytotoxicity and evoked a greater
immune response in macrophage RAW264.7 cells. Thus, it can be used as a better
wound-healing agent than AgNPs. Graphical AbstractFigurative representation of
the comparison of AgNPs and AgPyNPs in macrophage RAW264.7 cells in terms of
cytotoxicity and immune response.
PMID- 25852431
TI - Numerical study of natural convection in a horizontal cylinder filled with water
based alumina nanofluid.
AB - Natural heat convection of water-based alumina (Al2O3/water) nanofluids (with
volume fraction 1% and 4%) in a horizontal cylinder is numerically investigated.
The whole three-dimensional computational fluid dynamics (CFD) procedure is
performed in a completely open-source way. Blender, enGrid, OpenFOAM and ParaView
are employed for geometry creation, mesh generation, case simulation and post
process, respectively. Original solver 'buoyantBoussinesqSimpleFoam' is selected
for the present study, and a temperature-dependent solver
'buoyantBoussinesqSimpleTDFoam' is developed to ensure the simulation is more
realistic. The two solvers are used for same cases and compared to corresponding
experimental results. The flow regime in these cases is laminar (Reynolds number
is 150) and the Rayleigh number range is 0.7 * 10(7) ~ 5 * 10(7). By comparison,
the average natural Nusselt numbers of water and Al2O3/water nanofluids are found
to increase with the Rayleigh number. At the same Rayleigh number, the Nusselt
number is found to decrease with nanofluid volume fraction. The temperature
dependent solver is found better for water and 1% Al2O3/water nanofluid cases,
while the original solver is better for 4% Al2O3/water nanofluid cases.
Furthermore, due to strong three-dimensional flow features in the horizontal
cylinder, three-dimensional CFD simulation is recommended instead of two
dimensional simplifications.
PMID- 25852432
TI - Nucleation mechanism of nano-sized NaZn13-type and alpha-(Fe,Si) phases in La-Fe
Si alloys during rapid solidification.
AB - The nucleation mechanism involving rapid solidification of undercooled La-Fe-Si
melts has been studied experimentally and theoretically. The classical nucleation
theory-based simulations show a competitive nucleation process between the alpha
(Fe,Si) phase (size approximately 10 to 30 nm) and the cubic NaZn13-type phase
(hereinafter 1:13 phase, size approximately 200 to 400 nm) during rapid
solidification, and that the undercooled temperature change ?T plays an important
factor in this process. The simulated results about the nucleation rates of the
alpha-(Fe,Si) and 1:13 phases in La-Fe-Si ribbons fabricated by a melt-spinner
using a copper wheel with a surface speed of 35 m/s agree well with the XRD, SEM,
and TEM studies of the phase structure and microstructure of the ribbons. Our
study paves the way for designing novel La-Fe-Si materials for a wide range of
technological applications.
PMID- 25852433
TI - A facile hydrothermal approach to the synthesis of nanoscale rare earth
hydroxides.
AB - Nanosized rare earth (RE) hydroxides including La(OH)3, Nd(OH)3, Pr(OH)3,
Sm(OH)3, Gd(OH)3, and Er(OH)3 with rod-like morphology are fabricated via a
convenient hydrothermal approach. This strategy calls for the first preparation
of metal complexes between RE precursors and dodecylamine (DDA) in water/ethanol
mixture at room temperature and subsequent thermal decomposition at elevated
temperature. The influence of reaction time and water/ethanol volume ratios on
the morphology and size of as-prepared RE hydroxides are investigated. CeO2
nanoparticles with spherical shape could be directly obtained by hydrothermal
treatment of complexes formed between Ce precursors and DDA. In addition, by
further calcinating the RE hydroxides at high temperature in air, RE oxide
nanorods could be readily produced.
PMID- 25852434
TI - Bright, stable, and water-soluble CuInS2/ZnS nanocrystals passivated by
cetyltrimethylammonium bromide.
AB - We report a highly bright and stable aqueous dispersion of CuInS2/ZnS (CIS/ZnS)
nanocrystals (NCs) using surfactant-assisted microemulsion and cold treatment.
CIS/ZnS NCs were facilely synthesized via a stepwise, consecutive hybrid flow
reactor approach. To stabilize the optical properties of hydrophobic CIS/ZnS NCs,
cetyltrimethylammonium bromide (CTAB) was chosen as a matrix for aqueous phase
transfer. As the result, a high quantum yield (QY) of 56.0% and excellent
photostability were acquired in aqueous media. For removing excessive
surfactants, cold treatment (4 degrees C) of the CTAB-water solution was adopted
to prevent further agglomeration of CIS/ZnS NCs, which could secure high
stability over 6 months (less 2% reduction in QY). The optical features and
structure of the obtained CTAB stabilized CIS/ZnS (CTAB-CIS/ZnS) NCs have been
characterized by UV-vis and photoluminescence (PL) spectroscopies, XRD, XPS, EDX,
and TEM. The high stability and PL of water soluble CTAB-CIS/ZnS NCs suggest
their potential in nanoelectronics and bioapplications.
PMID- 25852435
TI - Quantum dot-sensitized solar cells having 3D-TiO2 flower-like structures on the
surface of titania nanorods with CuS counter electrode.
AB - The photovoltaic performance of a quantum dot (QD)-sensitized solar cell
consisting of CdS/CdSe/ZnS QDs loaded onto the surface of the three-dimensional
(3D) flower-like TiO2 structure grown on an array (1D) of TiO2 nanorods (FTiR) is
studied. The flower-like structure on the rod-shaped titania was synthesized
using a double-step hydrothermal process. The FTiR array exhibited a 3D/1D
composite structure with a specific surface area of 81.87 m(2)/g. Using CuS as
the counter electrode instead of Pt offers the best performance and leads to an
increase in the conversion efficiency (eta). The efficiency of the CdS/CdSe/ZnS
QD-loaded FTiR assembling CuS counter electrode cell improved from eta = 2.715%
(Voc = 0.692 V, Jsc = 5.896 mA/cm(2), FF = 0.665) to eta = 0.703% (Voc = 0.665 V,
Jsc = 2.108 mA/cm(2), FF = 0.501) for the QD-loaded FTiR assembling Pt counter
electrode cell. These studies reveal a synergistically beneficial effect on the
solar-to-current conversion of these QD-sensitized solar cells when a CuS counter
electrode is used instead of the usual Pt counter electrode.
PMID- 25852436
TI - Biosynthesis of gold nanoparticles assisted by the intracellular protein extract
of Pycnoporus sanguineus and its catalysis in degradation of 4-nitroaniline.
AB - The development of green procedure for the synthesis of gold nanoparticles
(AuNPs) has gained great interest in the field of nanotechnology. Biological
synthetic routes are considered to be environmentally benign and cost-effective.
In the present study, the feasibility of AuNPs' synthesis via intracellular
protein extract (IPE) of Pycnoporus sanguineus was explored. The characteristics
of generated particles of formation, crystalline nature, and morphology and
dimension were analyzed by UV-vis spectroscopy, X-ray diffraction (XRD) and
transmission electron microscopy (TEM), respectively. UV-vis spectra exhibited
strong absorption peaks in 520 to 560 nm, indicating the formation of AuNPs. XRD
analysis revealed that the formed AuNPs were purely crystalline in nature. TEM
observation showed that AuNPs with various shapes including spherical, pseudo
spherical, triangular, truncated triangular, pentagonal, and hexagonal, ranging
from several to several hundred nanometers, were synthesized under different
conditions. The average size of AuNPs decreased from 61.47 to 29.30 nm as the IPE
addition increased from 10 to 80 mL. When the initial gold ion concentration
changed from 0.5 to 2.0 mM, the average size rose from 25.88 to 51.99 nm. As in
the case of solution pH, the average size was 84.29 nm with solution pH of 2.0,
which diminished to 6.07 nm with solution pH of 12.0. Fourier transform infrared
(FTIR) analysis implied that the functional groups including hydroxyl, amine, and
carboxyl were involved in the reduction of gold ions and stabilization of AuNPs.
The catalysis results showed that 0.019 mg of AuNPs with average size of 6.07 nm
could catalyze the complete degradation of 12.5 MUmol of 4-nitroaniline within 6
min and the degradation rate increased drastically with the addition of AuNPs.
All the results suggested that the IPE of P. sanguineus could be potentially
applied for the eco-friendly synthesis of AuNPs.
PMID- 25852437
TI - Preparation of PEDOT/GO, PEDOT/MnO2, and PEDOT/GO/MnO2 nanocomposites and their
application in catalytic degradation of methylene blue.
AB - The nanocomposite materials of poly(3,4-ethylenedioxythiophene)/graphene oxide
(PEDOT/GO), poly(3,4-ethylenedioxythiophene)/MnO2 (PEDOT/MnO2), and poly(3, 4
ethylenedioxythiophene)/graphene oxide/MnO2 (PEDOT/GO/MnO2) were successfully
prepared by facile and template-free solution method. The structure and
morphology of nanonanocomposites were characterized by Fourier transform infrared
spectroscopy (FTIR), ultraviolet-visible absorption spectra (UV-vis), field
emission scanning electron microscope (FESEM), X-ray diffraction (XRD), and
energy-dispersive X-ray spectroscopy (EDX), respectively. The catalytic
activities of nanocomposites were investigated through the degradation processes
of methylene blue (MB) solution under dark, UV light, and nature sunlight
irradiation, respectively. The results displayed that nanocomposites were
successfully synthesized, and PEDOT/GO had higher conjugation length and doped
degree than pure PEDOT. However, the introduction of MnO2 could lead to the
reduction of conjugation length and doped degree in PEDOT/MnO2 and PEDOT/GO/MnO2
nanocomposites. The field emission scanning electron microscope (FESEM) analysis
also showed that both MnO2 and GO had some effect on the morphology of
nanocomposites. The catalytic activities of pure PEDOT and nanocomposites were in
the order of PEDOT/GO/MnO2 > PEDOT/MnO2 > PEDOT/GO > pure PEDOT. Besides, the
catalytic results also showed that the highest degradation efficiency of MB after
7 h occurred in the PEDOT/GO/MnO2 composite in three irradiation.
PMID- 25852438
TI - Effect of single-walled carbon nanotubes on tumor cells viability and formation
of multicellular tumor spheroids.
AB - ABSTRACT: This paper describes the impact of different concentrations of single
walled carbon nanotubes (SWCNTs) on cell viability of breast adenocarcinoma, MCF
7 line, and formation of multicellular tumor spheroids (MTS). Chemical
composition and purity of nanotubes is controlled by Fourier transform infrared
spectroscopy. The strength and direction of the influence of SWCNTs on the tumor
cell population was assessed by cell counting and measurement of the volume of
multicellular tumor spheroids. Effect of SWCNTs on the formation of multicellular
spheroids was compared with the results obtained by culturing tumor cells with
ultra dispersed diamonds (UDDs). Our results demonstrated that SWCNTs at
concentrations ranging from 12.5 to 50 MUg/ml did not have cytotoxic influence on
tumor cells; instead, they had weak cytostatic effect. The increasing of SWCNTs
concentration to 100 to 200 MUg/ml stimulated proliferation of tumor cells,
especially in suspension fractions. The result of this influence was in formation
of more MTS in cell culture with SWCNTs compared with UDDs and control samples.
In result, the median volume of MTS after cultivation with SWCNTs at 100 to 200
MUg/ml concentrations is 3 to 5 times greater than that in samples which were
incubated with the UDDs and is 2.5 times greater than that in control cultures.
So, if SWCNTs reduced cell adhesion to substrate and stimulated formation of
tumor cell aggregates volume near 7 . 10(-3) mm(3), at the same time, UDDs
reduced adhesion and cohesive ability of cells and stimulated generation of cell
spheroids volume no more than 4 . 10(-3) mm(3). Our results could be useful for
the control of cell growth in three-dimensional culture. PACS: 61. 46 + w; 61.48
+ c; 61.48De; 87.15-v; 87.64-t.
PMID- 25852439
TI - Random nanostructured metallic films for environmental monitoring and optical
sensing: experimental and computational studies.
AB - Nanostructured silver films are studied using computational and experimental
methods. Surface plasmon resonance-related phenomena are emphasized. Resonant
optical absorption band changes due to the influence of noxious gases are
investigated. Amplification of light at the film surface due to local
electromagnetic field enhancement at the nanoscale is discussed based on finite
difference time domain calculations.
PMID- 25852440
TI - Structural transformations in austenitic stainless steel induced by deuterium
implantation: irradiation at 100 K.
AB - Deuterium thermal desorption spectra were investigated on the samples of
austenitic stainless steel 18Cr10NiTi preimplanted at 100 K with deuterium ions
in the dose range from 3 * 10(15) to 5 * 10(18) D/cm(2). The kinetics of
structural transformation development in the implantation steel layer was traced
from deuterium thermodesorption spectra as a function of implanted deuterium
concentration. At saturation of austenitic stainless steel 18Cr10NiTi with
deuterium by means of ion implantation, structural-phase changes take place,
depending on the dose of implanted deuterium. The maximum attainable
concentration of deuterium in steel is C = 1 (at.D/at.met. = 1/1). The increase
in the implanted dose of deuterium is accompanied by the increase in the retained
deuterium content, and as soon as the deuterium concentration attains C ~ 0.5 the
process of shear martensitic structural transformation in steel takes place. It
includes the formation of bands, body-centered cubic (bcc) crystal structure, and
the ferromagnetic phase. Upon reaching the deuterium concentration C > 0.5, the
presence of these molecules causes shear martensitic structural transformations
in the steel, which include the formation of characteristic bands, bcc crystal
structure, and the ferromagnetic phase. At C >= 0.5, two hydride phases are
formed in the steel, the decay temperatures of which are 240 and 275 K. The
hydride phases are formed in the bcc structure resulting from the martensitic
structural transformation in steel.
PMID- 25852441
TI - SHANK Mutations May Disorder Brain Development.
PMID- 25852442
TI - Genomic sequencing and the impact of molecular diagnosis on patient care.
AB - Evolving sequencing technologies allow more accurate, efficient and affordable
genomic analysis. As a result, these technologies are increasingly available,
especially to provide molecular diagnoses for patients with suspected genetic
disorders. However, there are many challenges to using genomic sequencing to
benefit patients, including concerns that there is insufficient evidence that
identifying an underlying molecular explanation may positively impact a patient's
healthcare. This concern has many repercussions, including funding and/or (in
some countries and healthcare systems) insurance reimbursement for genomic
sequencing. To investigate this concern, all monogenic disorders were analyzed
based on the impact of achieving molecular diagnosis. Of the 2,849 individual
genes in which germline mutations cause disorders (not including contiguous gene
syndromes or what may be categorized as susceptibility alleles), our analyses
showed a specific, available intervention related to at least one affected organ
system for 1,419 (49.8%) genes. In 95.6% of these genes, the intervention(s)
would be recommended during the pediatric time frame.
PMID- 25852444
TI - Whole-Exome Sequencing in the Clinic: Lessons from Six Consecutive Cases from the
Clinician's Perspective.
AB - Whole-exome sequencing (WES) is being used clinically to diagnose rare Mendelian
disorders, especially when standard tests have failed. The diagnostic yield from
WES is reported to be ~15-30%; however, data regarding the clinical utility and
interpretative challenges from the clinician's perspective are lacking. Here, we
present a series of the first 6 unselected consecutive cases seen over a period
of 6 months where WES was employed in clinical labs via trio-based testing
(proband and parents). While we do not discount the value of WES in the clinical
setting, our cases and experience illustrate the significant clinical challenges
of WES, even when a diagnosis may be achieved.
PMID- 25852443
TI - Connecting the CNTNAP2 Networks with Neurodevelopmental Disorders.
AB - Based on genomic rearrangements and copy number variations, the contactin
associated protein-like 2 gene (CNTNAP2) has been implicated in
neurodevelopmental disorders such as Gilles de la Tourette syndrome, intellectual
disability, obsessive compulsive disorder, cortical dysplasia-focal epilepsy
syndrome, autism, schizophrenia, Pitt-Hopkins syndrome, and attention deficit
hyperactivity disorder. To explain the phenotypic pleiotropy of CNTNAP2
alterations, several hypotheses have been put forward. Those include gene
disruption, loss of a gene copy by a heterozygous deletion, altered regulation of
gene expression due to loss of transcription factor binding and DNA methylation
sites, and mutations in the amino acid sequence of the encoded protein which may
provoke altered interactions of the CNTNAP2-encoded protein, Caspr2, with other
proteins. Also exome sequencing, which covers <0.2% of the CNTNAP2 genomic DNA,
has revealed numerous single nucleotide variants in healthy individuals and in
patients with neurodevelopmental disorders. In some of these disorders,
disruption of CNTNAP2 may be interpreted as a susceptibility factor rather than a
directly causative mutation. In addition to being associated with impaired
development of language, CNTNAP2 may turn out to be a central node in the
molecular networks controlling neurodevelopment. This review discusses the impact
of CNTNAP2 mutations on its functioning at multiple levels of the combinatorial
genetic networks that govern brain development. In addition, recommendations for
genomic testing in the context of clinical genetic management of patients with
neurodevelopmental disorders and their families are put forward.
PMID- 25852446
TI - Cleft lip/palate, short stature, and developmental delay in a boy with a 5.6-mb
interstitial deletion involving 10p15.3p14.
AB - The chromosome interval 10p15.3p14 harbors about a dozen genes. This region has
been implicated in a few well-known human phenotypes, namely HDR syndrome
(hypoparathyroidism, sensorineural deafness, and renal dysplasia) and DGS2
(DiGeorge syndrome 2), but a number of variable phenotypes have also been
reported. Cleft lip/palate seems to be a very unusual finding within the clinical
spectrum of patients with this deletion. Here, we report a male child born with
short stature, cleft lip/palate, and feeding problems who was found to have a 5.6
Mb deletion at 10p15.3p14.
PMID- 25852447
TI - A novel mutation in the endothelin B receptor gene in a moroccan family with shah
waardenburg syndrome.
AB - Waardenburg syndrome (WS) is a neurocristopathy disorder combining sensorineural
deafness and pigmentary abnormalities. The presence of additional signs defines
the 4 subtypes. WS type IV, also called Shah-Waardenburg syndrome (SWS), is
characterized by the association with congenital aganglionic megacolon
(Hirschsprung disease). To date, 3 causative genes have been related to this
congenital disorder. Mutations in the EDNRB and EDN3 genes are responsible for
the autosomal recessive form of SWS, whereas SOX10 mutations are inherited in an
autosomal dominant manner. We report here the case of a 3-month-old Morrocan girl
with WS type IV, born to consanguineous parents. The patient had 3 cousins who
died in infancy with the same symptoms. Molecular analysis by Sanger sequencing
revealed the presence of a novel homozygous missense mutation c.1133A>G
(p.Asn378Ser) in the EDNRB gene. The proband's parents as well as the parents of
the deceased cousins are heterozygous carriers of this likely pathogenic
mutation. This molecular diagnosis allows us to provide genetic counseling to the
family and eventually propose prenatal diagnosis to prevent recurrence of the
disease in subsequent pregnancies.
PMID- 25852445
TI - Clinical and molecular heterogeneity in brazilian patients with sotos syndrome.
AB - Sotos syndrome (SoS) is a multiple anomaly, congenital disorder characterized by
overgrowth, macrocephaly, distinctive facial features and variable degree of
intellectual disability. Haploinsufficiency of the NSD1 gene at 5q35.3, arising
from 5q35 microdeletions, point mutations, and partial gene deletions, accounts
for a majority of patients with SoS. Recently, mutations and possible
pathogenetic rare CNVs, both affecting a few candidate genes for overgrowth, have
been reported in patients with Sotos-like overgrowth features. To estimate the
frequency of NSD1 defects in the Brazilian SoS population and possibly reveal
other genes implicated in the etiopathogenesis of this syndrome, we collected a
cohort of 21 Brazilian patients, who fulfilled the diagnostic criteria for SoS,
and analyzed the NSD1 and PTEN genes by means of multiplex ligation-dependent
probe amplification and mutational screening analyses. We identified a classical
NSD1 microdeletion, a novel missense mutation (p.C1593W), and 2 previously
reported truncating mutations: p.R1984X and p.V1760Gfs*2. In addition, we
identified a novel de novo PTEN gene mutation (p.D312Rfs*2) in a patient with a
less severe presentation of SoS phenotype, which did not include pre- and
postnatal overgrowth. For the first time, our study implies PTEN in the
pathogenesis of SoS and further emphasizes the existence of ethno-geographical
differences in NSD1 molecular alterations between patients with SoS from
Europe/North America (70-93%) and those from South America (10-19%).
PMID- 25852448
TI - A Glutamine Repeat Variant of the RUNX2 Gene Causes Cleidocranial Dysplasia.
AB - Cleidocranial dysplasia (CCD), an autosomal dominant skeletal dysplasia
characterized by hypoplastic clavicles and delayed closure of the cranial
sutures, is caused by mutations of the runt-related transcription factor 2
(RUNX2) gene. The RUNX2 gene consists of a glutamine and alanine repeat domain
(Q/A domain, 23Q/17A), a DNA-binding Runt domain and a proline/serine/threonine
rich domain. We report on a familial case of CCD with a novel mutation within the
Q/A domain of the RUNX2 gene, which is an insertion in exon 1 (p.Q71_E72insQQQQ)
representing the Q-repeat variant (27Q/17A). Functional analysis of the 27Q
variant revealed abolished transactivation capacity of the mutated RUNX2 protein.
This is the first case report that demonstrated a glutamine repeat variant of the
RUNX2 gene causes CCD.
PMID- 25852449
TI - Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL
study.
AB - Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by
orthostatic intolerance, and is frequently accompanied by a range of symptoms
including palpitations, lightheadedness, clouding of thought, blurred vision,
fatigue, anxiety, and depression. Although the estimated prevalence of PoTS is
approximately 5-10 times as common as the better-known condition orthostatic
hypotension, the neural substrates of the syndrome are poorly characterized. In
the present study, we used magnetic resonance imaging (MRI) with voxel-based
morphometry (VBM) applying the diffeomorphic anatomical registration through
exponentiated lie algebra (DARTEL) procedure to examine variation in regional
brain structure associated with PoTS. We recruited 11 patients with established
PoTS and 23 age-matched normal controls. Group comparison of gray matter volume
revealed diminished gray matter volume within the left anterior insula, right
middle frontal gyrus and right cingulate gyrus in the PoTS group. We also
observed lower white matter volume beneath the precentral gyrus and paracentral
lobule, right pre- and post-central gyrus, paracentral lobule and superior
frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant
negative correlations between left insula volume and trait anxiety and depression
scores. Together, these findings of structural differences, particularly within
insular and cingulate components of the salience network, suggest a link between
dysregulated physiological reactions arising from compromised central autonomic
control (and interoceptive representation) and increased vulnerability to
psychiatric symptoms in PoTS patients.
PMID- 25852450
TI - Amyloid-beta oligomers unveil a novel primate model of sporadic Alzheimer's
disease.
PMID- 25852452
TI - Cognitive mechanisms underlying instructed choice exploration of small city maps.
AB - We investigated the cognitive mechanisms underlying the exploration and decision
making in realistic and novel environments. Twelve human subjects were shown
small circular U.S. city maps with two locations highlighted on the
circumference, as possible choices for a post office ("targets"). At the
beginning of a trial, subjects fixated a spot at the center of the map and
ultimately chose one of the two locations. A space syntax analysis of the map
paths (from the center to each target) revealed that the chosen location was
associated with the less convoluted path, as if subjects navigated mentally the
paths in an "ant's way," i.e., by staying within street boundaries, and
ultimately choosing the target that could be reached from the center in the
shortest way, and the fewest turns and intersections. The subjects' strategy for
map exploration and decision making was investigated by monitoring eye position
during the task. This revealed a restricted exploration of the map delimited by
the location of the two alternative options and the center of the map.
Specifically, subjects explored the areas around the two target options by
repeatedly looking at them before deciding which one to choose, presumably
implementing an evaluation and decision-making process. The ultimate selection of
a specific target was significantly associated with the time spent exploring the
area around that target. Finally, an analysis of the sequence of eye fixations
revealed that subjects tended to look systematically toward the target ultimately
chosen even from the beginning of the trial. This finding indicates an early
cognitive selection bias for the ensuing decision process.
PMID- 25852451
TI - The ecology of human fear: survival optimization and the nervous system.
AB - We propose a Survival Optimization System (SOS) to account for the strategies
that humans and other animals use to defend against recurring and novel threats.
The SOS attempts to merge ecological models that define a repertoire of
contextually relevant threat induced survival behaviors with contemporary
approaches to human affective science. We first propose that the goal of the
nervous system is to reduce surprise and optimize actions by (i) predicting the
sensory landscape by simulating possible encounters with threat and selecting the
appropriate pre-encounter action and (ii) prevention strategies in which the
organism manufactures safe environments. When a potential threat is encountered
the (iii) threat orienting system is engaged to determine whether the organism
ignores the stimulus or switches into a process of (iv) threat assessment, where
the organism monitors the stimulus, weighs the threat value, predicts the actions
of the threat, searches for safety, and guides behavioral actions crucial to
directed escape. When under imminent attack, (v) defensive systems evoke fast
reflexive indirect escape behaviors (i.e., fight or flight). This cascade of
responses to threat of increasing magnitude are underwritten by an interconnected
neural architecture that extends from cortical and hippocampal circuits, to
attention, action and threat systems including the amygdala, striatum, and hard
wired defensive systems in the midbrain. The SOS also includes a modulatory
feature consisting of cognitive appraisal systems that flexibly guide perception,
risk and action. Moreover, personal and vicarious threat encounters fine-tune
avoidance behaviors via model-based learning, with higher organisms bridging data
to reduce face-to-face encounters with predators. Our model attempts to unify the
divergent field of human affective science, proposing a highly integrated nervous
system that has evolved to increase the organism's chances of survival.
PMID- 25852453
TI - Estradiol-sensitive projection neurons in the female rat preoptic area.
AB - Electrical stimulation of the preoptic area (POA) interrupts the lordosis reflex,
a combined contraction of back muscles, in response to male mounts and the major
receptive component of sexual behavior in female rat in estrus, without
interfering with the proceptive component of this behavior or solicitation. Axon
sparing POA lesions with an excitotoxin, on the other hand, enhance lordosis and
diminish proceptivity. The POA effect on the reflex is mediated by its estrogen
sensitive projection to the ventral tegmental area (VTA) as shown by the
behavioral effect of VTA stimulation as well as by the demonstration of an
increased threshold for antidromic activation of POA neurons from the VTA in
ovariectomized females treated with estradiol benzoate (EB). EB administration
increases the antidromic activation threshold in ovariectomized females and
neonatally castrated males, but not in neonatally androgenized females; the EB
effect is limited to those that show lordosis in the presence of EB. EB causes
behavioral disinhibition of lordosis through an inhibition of POA neurons with
axons to the VTA, which eventually innervate medullospinal neurons innervating
spinal motoneurons of the back muscle. The EB-induced change in the threshold or
the axonal excitability may be a result of EB-dependent induction of BK channels.
Recordings from freely moving female rats engaging in sexual interactions
revealed separate subpopulations of POA neurons for the receptive and proceptive
behaviors. Those POA neurons engaging in the control of proceptivity are EB
sensitive and project to the midbrain locomotor region (MLR). EB thus enhances
lordosis by reducing excitatory neural impulses from the POA to the VTA. An
augmentation of the POA effect to the MLR may culminate in an increased
locomotion that embodies behavioral estrus in the female rat.
PMID- 25852454
TI - Spinal primitives and intra-spinal micro-stimulation (ISMS) based prostheses: a
neurobiological perspective on the "known unknowns" in ISMS and future prospects.
AB - The current literature on Intra-Spinal Micro-Stimulation (ISMS) for motor
prostheses is reviewed in light of neurobiological data on spinal organization,
and a neurobiological perspective on output motor modularity, ISMS maps,
stimulation combination effects, and stability. By comparing published data in
these areas, the review identifies several gaps in current knowledge that are
crucial to the development of effective intraspinal neuroprostheses. Gaps can be
categorized into a lack of systematic and reproducible details of: (a) Topography
and threshold for ISMS across the segmental motor system, the topography of
autonomic recruitment by ISMS, and the coupling relations between these two types
of outputs in practice. (b) Compositional rules for ISMS motor responses tested
across the full range of the target spinal topographies. (c) Rules for ISMS
effects' dependence on spinal cord state and neural dynamics during naturally
elicited or ISMS triggered behaviors. (d) Plasticity of the compositional rules
for ISMS motor responses, and understanding plasticity of ISMS topography in
different spinal cord lesion states, disease states, and following
rehabilitation. All these knowledge gaps to a greater or lesser extent require
novel electrode technology in order to allow high density chronic recording and
stimulation. The current lack of this technology may explain why these prominent
gaps in the ISMS literature currently exist. It is also argued that given the
"known unknowns" in the current ISMS literature, it may be prudent to adopt and
develop control schemes that can manage the current results with simple
superposition and winner-take-all interactions, but can also incorporate the
possible plastic and stochastic dynamic interactions that may emerge in fuller
analyses over longer terms, and which have already been noted in some simpler
model systems.
PMID- 25852455
TI - Effect of social odor context on the emission of isolation-induced ultrasonic
vocalizations in the BTBR T+tf/J mouse model for autism.
AB - An important diagnostic criterion for social communication deficits in autism
spectrum disorders (ASD) are difficulties in adjusting behavior to suit different
social contexts. While the BTBR T+tf/J (BTBR) inbred strain of mice is one of the
most commonly used mouse models for ASD, little is known about whether BTBR mice
display deficits in detecting changes in social context and their ability to
adjust to them. Here, it was tested therefore whether the emission of isolation
induced ultrasonic vocalizations (USV) in BTBR mouse pups is affected by the
social odor context, in comparison to the standard control strain with high
sociability, C57BL/6J (B6). It is known that the presence of odors from mothers
and littermates leads to a calming of the isolated mouse pup, and hence to a
reduction in isolation-induced USV emission. In accordance with their behavioral
phenotypes with relevance to all diagnostic core symptoms of ASD, it was
predicted that BTBR mouse pups would not display a calming response when tested
under soiled bedding conditions with home cage bedding material containing
maternal odors, and that similar isolation-induced USV emission rates would be
seen in BTBR mice tested under clean and soiled bedding conditions. Unexpectedly,
however, the present findings show that BTBR mouse pups display such a calming
response and emit fewer isolation-induced USV when tested under soiled as
compared to clean bedding conditions, similar to B6 mouse pups. Yet, in contrast
to B6 mouse pups, which emitted isolation-induced USV with shorter call durations
and lower levels of frequency modulation under soiled bedding conditions, social
odor context had no effect on acoustic call features in BTBR mouse pups. This
indicates that the BTBR mouse model for ASD does not display deficits in
detecting changes in social context, but has a limited ability and/or reduced
motivation to adjust to them.
PMID- 25852456
TI - Outer brain barriers in rat and human development.
AB - Complex barriers at the brain's surface, particularly in development, are poorly
defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier
separates the fenestrated dural vessels from the CSF by means of a cell layer
joined by tight junctions. Outer CSF-brain barrier provides diffusion restriction
between brain and subarachnoid CSF through an initial radial glial end feet layer
covered with a pial surface layer. To further characterize these interfaces we
examined embryonic rat brains from E10 to P0 and forebrains from human embryos
and fetuses (6-21st weeks post-conception) and adults using immunohistochemistry
and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4,
MAP2, YKL-40, and its receptor IL-13Ralpha2 and EAAT1 were used to describe
morphological characteristics and functional aspects of the outer brain barriers.
Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1
delineated the subarachnoid space and stained pial surface layer. BLBP defined
radial glial end feet layer and SSEA-4 and YKL-40 were present in both
leptomeningeal cells and end feet layer, which transformed into glial limitans.
IL-13Ralpha2 and EAAT1 were present in the end feet layer illustrating
transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining
in adult brain outlined the lower border of glia limitans; remnants of end feet
were YKL-40 positive in some areas. We propose that outer brain barriers are
composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier
cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain
barrier comprising glial end feet layer/pial surface layer.
PMID- 25852457
TI - Functional significance of the electrocorticographic auditory responses in the
premotor cortex.
AB - Other than well-known motor activities in the precentral gyrus, functional
magnetic resonance imaging (fMRI) studies have found that the ventral part of the
precentral gyrus is activated in response to linguistic auditory stimuli. It has
been proposed that the premotor cortex in the precentral gyrus is responsible for
the comprehension of speech, but the precise function of this area is still
debated because patients with frontal lesions that include the precentral gyrus
do not exhibit disturbances in speech comprehension. We report on a patient who
underwent resection of the tumor in the precentral gyrus with
electrocorticographic recordings while she performed the verb generation task
during awake brain craniotomy. Consistent with previous fMRI studies, high-gamma
band auditory activity was observed in the precentral gyrus. Due to the location
of the tumor, the patient underwent resection of the auditory responsive
precentral area which resulted in the post-operative expression of a
characteristic articulatory disturbance known as apraxia of speech (AOS). The
language function of the patient was otherwise preserved and she exhibited intact
comprehension of both spoken and written language. The present findings
demonstrated that a lesion restricted to the ventral precentral gyrus is
sufficient for the expression of AOS and suggest that the auditory-responsive
area plays an important role in the execution of fluent speech rather than the
comprehension of speech. These findings also confirm that the function of the
premotor area is predominantly motor in nature and its sensory responses is more
consistent with the "sensory theory of speech production," in which it was
proposed that sensory representations are used to guide motor-articulatory
processes.
PMID- 25852458
TI - Effects of diethylstilbestrol exposure during gestation on both maternal and
offspring behavior.
AB - Endocrine disruption during gestation impairs the physical and behavioral
development of offspring. However, it is unclear whether endocrine disruption
also impairs maternal behavior and in turn further contributes to the
developmental and behavioral dysfunction of offspring. We orally administered the
synthetic non-steroidal estrogen diethylstilbestrol (DES) to pregnant female
C57BL/6J mice from gestation day 11-17 and then investigated the maternal
behavior of mothers. In addition, we examined the direct effects of in utero DES
exposure and the indirect effects of aberrant maternal behavior on offspring
using the cross-fostering method. In mothers, endocrine disruption during
gestation decreased maternal behavior. In addition, endocrine disruption of
foster mother influenced anxiety-related behavior and passive avoidance learning
of pups regardless of their exposure in utero. The influence of DES exposure in
utero, irrespective of exposure to the foster mother, was also shown in female
offspring. These results demonstrate the risks of endocrine disruptors on both
mother as well as offspring and suggest that developmental deficits may stem from
both in utero toxicity and aberrant maternal care.
PMID- 25852459
TI - Local modulation of steroid action: rapid control of enzymatic activity.
AB - Estrogens can induce rapid, short-lived physiological and behavioral responses,
in addition to their slow, but long-term, effects at the transcriptional level.
To be functionally relevant, these effects should be associated with rapid
modulations of estrogens concentrations. 17beta-estradiol is synthesized by the
enzyme aromatase, using testosterone as a substrate, but can also be degraded
into catechol-estrogens via hydroxylation by the same enzyme, leading to an
increase or decrease in estrogens concentration, respectively. The first evidence
that aromatase activity (AA) can be rapidly modulated came from experiments
performed in Japanese quail hypothalamus homogenates. This rapid modulation is
triggered by calcium-dependent phosphorylations and was confirmed in other
tissues and species. The mechanisms controlling the phosphorylation status, the
targeted amino acid residues and the reversibility seem to vary depending of the
tissues and is discussed in this review. We currently do not know whether the
phosphorylation of the same amino acid affects both aromatase and/or hydroxylase
activities or whether these residues are different. These processes provide a new
general mechanism by which local estrogen concentration can be rapidly altered in
the brain and other tissues.
PMID- 25852460
TI - The role of metabotropic glutamate receptor 5 in the pathogenesis of mood
disorders and addiction: combining preclinical evidence with human Positron
Emission Tomography (PET) studies.
AB - In the present review, we deliver an overview of the involvement of metabotropic
glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood
disorders and addiction. Specifically, we will describe mGluR5 studies in humans
that employed Positron Emission Tomography (PET) and combined the findings with
preclinical animal research. This combined view of different methodological
approaches-from basic neurobiological approaches to human studies-might give a
more comprehensive and clinically relevant view of mGluR5 function in mental
health than the view on preclinical data alone. We will also review the current
research data on mGluR5 along the Research Domain Criteria (RDoC). Firstly, we
found evidence of abnormal glutamate activity related to the positive and
negative valence systems, which would suggest that antagonistic mGluR5
intervention has prominent anti-addictive, anti-depressive and anxiolytic
effects. Secondly, there is evidence that mGluR5 plays an important role in
systems for social functioning and the response to social stress. Finally,
mGluR5's important role in sleep homeostasis suggests that this glutamate
receptor may play an important role in RDoC's arousal and modulatory systems
domain. Glutamate was previously mostly investigated in non-human studies,
however initial human clinical PET research now also supports the hypothesis
that, by mediating brain excitability, neuroplasticity and social cognition,
abnormal metabotropic glutamate activity might predispose individuals to a broad
range of psychiatric problems.
PMID- 25852461
TI - Spatiotemporal analyses of neural lineages after embryonic and postnatal
progenitor targeting combining different reporters.
AB - Genetic lineage tracing with electroporation is one of the most powerful
techniques to target neural progenitor cells and their progeny. However, the
spatiotemporal relationship between neural progenitors and their final phenotype
remain poorly understood. One critical factor to analyze the cell fate of progeny
is reporter integration into the genome of transfected cells. To address this
issue, we performed postnatal and in utero co-electroporations of different
fluorescent reporters to label, in both cerebral cortex and olfactory bulb, the
progeny of subventricular zone neural progenitors. By comparing fluorescent
reporter expression in the adult cell progeny, we show a differential expression
pattern within the same cell lineage, depending on electroporation stage and cell
identity. Further, while neuronal lineages arise from many progenitors in
proliferative zones after few divisions, glial lineages come from fewer
progenitors that accomplish many cell divisions. Together, these data provide a
useful guide to select a strategy to track the cell fate of a specific cell
population and to address whether a different proliferative origin might be
correlated with functional heterogeneity.
PMID- 25852462
TI - Collaborative mining of public data resources in neuroinformatics.
PMID- 25852465
TI - Corrigendum: Hypothalamic miRNAs: emerging roles in energy balance control.
AB - [This corrects the article on p. 41 in vol. 9, PMID: 25729348.].
PMID- 25852464
TI - Neurotoxic effects of AZT on developing and adult neurogenesis.
AB - Azidothymidine (AZT) is a synthetic, chain-terminating nucleoside analog used to
treat HIV-1 infection. While AZT is not actively transported across the blood
brain barrier, it does accumulate at high levels in cerebrospinal fluid, and
subsequently diffuses into the overlying parenchyma. Due to the close anatomical
proximity of the neurogenic niches to the ventricular system, we hypothesize that
diffusion from CSF exposes neural stem/progenitor cells and their progeny to
biologically relevant levels of AZT sufficient to perturb normal cell functions.
We employed in vitro and in vivo models of mouse neurogenesis in order to assess
the effects of AZT on developing and adult neurogenesis. Using in vitro assays we
show that AZT reduces the population expansion potential of neural
stem/progenitor cells by inducing senescence. Additionally, in a model of in
vitro neurogenesis AZT severely attenuates neuroblast production. These effects
are mirrored in vivo by clinically-relevant animal models. We show that in utero
AZT exposure perturbs both population expansion and neurogenesis among neural
stem/progenitor cells. Additionally, a short-term AZT regimen in adult mice
suppresses subependymal zone neurogenesis. These data reveal novel negative
effects of AZT on neural stem cell biology. Given that the sequelae of HIV
infection often include neurologic deficits-subsumed under AIDS Dementia Complex
(Brew, 1999)-it is important to determine to what extent AZT negatively affects
neurological function in ways that contribute to, or exacerbate, ADC in order to
avoid attributing iatrogenic drug effects to the underlying disease process, and
thereby skewing the risk/benefit analysis of AZT therapy.
PMID- 25852463
TI - GLP-1 based therapeutics: simultaneously combating T2DM and obesity.
AB - Glucagon-like peptide-1 (GLP-1) enhances meal-related insulin secretion, which
lowers blood glucose excursions. In addition to its incretin action, GLP-1 acts
on the GLP-1 receptor (GLP-1R) in the brain to suppress feeding. These combined
actions of GLP-1R signaling cause improvements in glycemic control as well as
weight loss in type II diabetes (T2DM) patients treated with GLP-1R agonists.
This is a superior advantage of GLP-1R pharmaceuticals as many other drugs used
to treat T2DM are weight neutral or actual cause weight gain. This review
summarizes GLP-1R action on energy and glucose metabolism, the effectiveness of
current GLP-1R agonists on weight loss in T2DM patients, as well as GLP-1R
combination therapies.
PMID- 25852466
TI - Proteoglycans and neuronal migration in the cerebral cortex during development
and disease.
AB - Chondroitin sulfate proteoglycans and heparan sulfate proteoglycans are major
constituents of the extracellular matrix and the cell surface in the brain.
Proteoglycans bind with many proteins including growth factors, chemokines, axon
guidance molecules, and cell adhesion molecules through both the
glycosaminoglycan and the core protein portions. The functions of proteoglycans
are flexibly regulated due to the structural variability of glycosaminoglycans,
which are generated by multiple glycosaminoglycan synthesis and modifying
enzymes. Neuronal cell surface proteoglycans such as PTPzeta, neuroglycan C and
syndecan-3 function as direct receptors for heparin-binding growth factors that
induce neuronal migration. The lectican family, secreted chondroitin sulfate
proteoglycans, forms large aggregates with hyaluronic acid and tenascins, in
which many signaling molecules and enzymes including matrix proteases are
preserved. In the developing cerebrum, secreted chondroitin sulfate proteoglycans
such as neurocan, versican and phosphacan are richly expressed in the areas that
are strategically important for neuronal migration such as the striatum, marginal
zone, subplate and subventricular zone in the neocortex. These proteoglycans may
anchor various attractive and/or repulsive cues, regulating the migration routes
of inhibitory neurons. Recent studies demonstrated that the genes encoding
proteoglycan core proteins and glycosaminoglycan synthesis and modifying enzymes
are associated with various psychiatric and intellectual disorders, which may be
related to the defects of neuronal migration.
PMID- 25852468
TI - Non-additive modulation of synaptic transmission by serotonin, adenosine, and
cholinergic modulators in the sensory thalamus.
AB - The thalamus relays sensory information to the cortex. Oscillatory activities of
the thalamocortical network are modulated by monoamines, acetylcholine, and
adenosine, and could be the key features characteristic of different vigilance
states. Although the thalamus is almost always subject to the actions of more
than just one neuromodulators, reports on the modulatory effect of coexisting
neuromodulators on thalamic synaptic transmission are unexpectedly scarce. We
found that, if present alone, monoamine or adenosine decreases retinothalamic
synaptic strength and short-term depression, whereas cholinergic modulators
generally enhance postsynaptic response to presynaptic activity. However,
coexistence of different modulators tends to produce non-additive effect, not
predictable based on the action of individual modulators. Acetylcholine, acting
via nicotinic receptors, can interact with either serotonin or adenosine to
abolish most short-term synaptic depression. Moreover, the coexistence of
adenosine and monoamine, with or without acetylcholine, results in robustly
decreased synaptic strength and transforms short-term synaptic depression to
facilitation. These findings are consistent with a view that acetylcholine is
essential for an "enriched" sensory flow through the thalamus, and the flow is
trimmed down by concomitant monoamine or adenosine (presumably for the
wakefulness and rapid-eye movement, or REM, sleep states, respectively). In
contrast, concomitant adenosine and monoamine would lead to a markedly "deprived"
(and high-pass filtered) sensory flow, and thus the dramatic decrease of
monoamine may constitute the basic demarcation between non-REM and REM sleep. The
collective actions of different neuromodulators on thalamic synaptic transmission
thus could be indispensable for the understanding of network responsiveness in
different vigilance states.
PMID- 25852469
TI - Polarity transitions during neurogenesis and germinal zone exit in the developing
central nervous system.
AB - During neural development, billions of neurons differentiate, polarize, migrate
and form synapses in a precisely choreographed sequence. These precise
developmental events are accompanied by discreet transitions in cellular
polarity. While radial glial neural stem cells are highly polarized, transiently
amplifying neural progenitors are less polarized after delaminating from their
parental stem cell. Moreover, preceding their radial migration to a final laminar
position neural progenitors re-adopt a polarized morphology before they embarking
on their journey along a glial guide to the destination where they will fully
mature. In this review, we will compare and contrast the key polarity transitions
of cells derived from a neuroepithelium to the well-characterized polarity
transitions that occur in true epithelia. We will highlight recent advances in
the field that shows that neuronal progenitor delamination from germinal zone
(GZ) niche shares similarities to an epithelial-mesenchymal transition. Moreover,
studies in the cerebellum suggest the acquisition of radial migration and
polarity in transiently amplifying neural progenitors share similarities to
mesenchymal-epithelial transitions. Where applicable, we will compare and
contrast the precise molecular mechanisms used by epithelial cells and neuronal
progenitors to control plasticity in cell polarity during their distinct
developmental programs.
PMID- 25852470
TI - Contribution of sublinear and supralinear dendritic integration to neuronal
computations.
AB - Nonlinear dendritic integration is thought to increase the computational ability
of neurons. Most studies focus on how supralinear summation of excitatory
synaptic responses arising from clustered inputs within single dendrites result
in the enhancement of neuronal firing, enabling simple computations such as
feature detection. Recent reports have shown that sublinear summation is also a
prominent dendritic operation, extending the range of subthreshold input-output
(sI/O) transformations conferred by dendrites. Like supralinear operations,
sublinear dendritic operations also increase the repertoire of neuronal
computations, but feature extraction requires different synaptic connectivity
strategies for each of these operations. In this article we will review the
experimental and theoretical findings describing the biophysical determinants of
the three primary classes of dendritic operations: linear, sublinear, and
supralinear. We then review a Boolean algebra-based analysis of simplified neuron
models, which provides insight into how dendritic operations influence neuronal
computations. We highlight how neuronal computations are critically dependent on
the interplay of dendritic properties (morphology and voltage-gated channel
expression), spiking threshold and distribution of synaptic inputs carrying
particular sensory features. Finally, we describe how global (scattered) and
local (clustered) integration strategies permit the implementation of similar
classes of computations, one example being the object feature binding problem.
PMID- 25852467
TI - A network of RNA and protein interactions in Fronto Temporal Dementia.
AB - Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by
degeneration of the fronto temporal lobes and abnormal protein inclusions. It
exhibits a broad clinicopathological spectrum and has been linked to mutations in
seven different genes. We will provide a picture, which connects the products of
these genes, albeit diverse in nature and function, in a network. Despite the
paucity of information available for some of these genes, we believe that RNA
processing and post-transcriptional regulation of gene expression might
constitute a common theme in the network. Recent studies have unraveled the role
of mutations affecting the functions of RNA binding proteins and regulation of
microRNAs. This review will combine all the recent findings on genes involved in
the pathogenesis of FTD, highlighting the importance of a common network of
interactions in order to study and decipher the heterogeneous clinical
manifestations associated with FTD. This approach could be helpful for the
research of potential therapeutic strategies.
PMID- 25852471
TI - The neural stem cell fate determinant TRIM32 regulates complex behavioral traits.
AB - In mammals, new neurons are generated throughout the entire lifespan in two
restricted areas of the brain, the dentate gyrus (DG) of the hippocampus and the
subventricular zone (SVZ)-olfactory bulb (OB) system. In both regions newborn
neurons display unique properties that clearly distinguish them from mature
neurons. Enhanced excitability and increased synaptic plasticity enables them to
add specific properties to information processing by modulating the existing
local circuitry of already established mature neurons. Hippocampal neurogenesis
has been suggested to play a role in spatial-navigation learning, spatial memory,
and spatial pattern separation. Cumulative evidences implicate that adult-born OB
neurons contribute to learning processes and odor memory. We recently
demonstrated that the cell fate determinant TRIM32 is upregulated in
differentiating neuroblasts of the SVZ-OB system in the adult mouse brain. The
absence of TRIM32 leads to increased progenitor cell proliferation and less cell
death. Both effects accumulate in an overproduction of adult-generated OB
neurons. Here, we present novel data from behavioral studies showing that such an
enhancement of OB neurogenesis not necessarily leads to increased olfactory
performance but in contrast even results in impaired olfactory capabilities. In
addition, we show at the cellular level that TRIM32 protein levels increase
during differentiation of neural stem cells (NSCs). At the molecular level,
several metabolic intermediates that are connected to glycolysis, glycine, or
cysteine metabolism are deregulated in TRIM32 knockout mice brain tissue. These
metabolomics pathways are directly or indirectly linked to anxiety or depression
like behavior. In summary, our study provides comprehensive data on how the
impairment of neurogenesis caused by the loss of the cell fate determinant TRIM32
causes a decrease of olfactory performance as well as a deregulation of
metabolomic pathways that are linked to mood disorders.
PMID- 25852472
TI - Astrocyte heterogeneity in the brain: from development to disease.
AB - In the last decades, astrocytes have risen from passive supporters of neuronal
activity to central players in brain function and cognition. Likewise, the
heterogeneity of astrocytes starts to become recognized in contrast to the
homogeneous population previously predicted. In this review, we focused on
astrocyte heterogeneity in terms of their morphological, protein expression and
functional aspects, and debate in a historical perspective the diversity
encountered in glial progenitors and how they may reflect mature astrocyte
heterogeneity. We discussed data that show that different progenitors may have
unsuspected roles in developmental processes. We have approached the functions of
astrocyte subpopulations on the onset of psychiatric and neurological diseases.
PMID- 25852473
TI - Alteration of synaptic connectivity of oligodendrocyte precursor cells following
demyelination.
AB - Oligodendrocyte precursor cells (OPCs) are a major source of remyelinating
oligodendrocytes in demyelinating diseases such as Multiple Sclerosis (MS). While
OPCs are innervated by unmyelinated axons in the normal brain, the fate of such
synaptic contacts after demyelination is still unclear. By combining
electrophysiology and immunostainings in different transgenic mice expressing
fluorescent reporters, we studied the synaptic innervation of OPCs in the model
of lysolecithin (LPC)-induced demyelination of corpus callosum. Synaptic
innervation of reactivated OPCs in the lesion was revealed by the presence of
AMPA receptor-mediated synaptic currents, VGluT1+ axon-OPC contacts in 3D
confocal reconstructions and synaptic junctions observed by electron microscopy.
Moreover, 3D confocal reconstructions of VGluT1 and NG2 immunolabeling showed the
existence of glutamatergic axon-OPC contacts in post-mortem MS lesions.
Interestingly, patch-clamp recordings in LPC-induced lesions demonstrated a
drastic decrease in spontaneous synaptic activity of OPCs early after
demyelination that was not caused by an impaired conduction of compound action
potentials. A reduction in synaptic connectivity was confirmed by the lack of
VGluT1+ axon-OPC contacts in virtually all rapidly proliferating OPCs stained
with EdU (50-ethynyl-20-deoxyuridine). At the end of the massive proliferation
phase in lesions, the proportion of innervated OPCs rapidly recovers, although
the frequency of spontaneous synaptic currents did not reach control levels. In
conclusion, our results demonstrate that newly-generated OPCs do not receive
synaptic inputs during their active proliferation after demyelination, but gain
synapses during the remyelination process. Hence, glutamatergic synaptic inputs
may contribute to inhibit OPC proliferation and might have a physiopathological
relevance in demyelinating disorders.
PMID- 25852474
TI - PPARbeta/delta and PPARgamma maintain undifferentiated phenotypes of mouse adult
neural precursor cells from the subventricular zone.
AB - The subventricular zone (SVZ) is one of the main niches of neural stem cells in
the adult mammalian brain. Stem and precursor cells in this region are the source
for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus
callosum, respectively. The identification of the molecular components regulating
the decision of these cells to differentiate or maintain an undifferentiated
state is important in order to understand the modulation of neurogenic processes
in physiological and pathological conditions. PPARs are a group of transcription
factors, activated by lipid ligands, with important functions in cellular
differentiation and proliferation in several tissues. In this work, we
demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro,
express PPARbeta/delta and PPARgamma. Pharmacological activation of both PPARs
isoforms induces proliferation and maintenance of the undifferentiated phenotype.
Congruently, inhibition of PPARbeta/delta and PPARgamma results in a decrease of
proliferation and loss of the undifferentiated phenotype. Interestingly,
PPARgamma regulates the level of EGFR in adult NPCs, concurrent with it is
function described in embryonic NPCs. Furthermore, we describe for the first time
that PPARbeta/delta regulates SOX2 level in adult NPCs, probably through a direct
transcriptional regulation, as we identified two putative PPAR response elements
in the promoter region of Sox2. EGFR and SOX2 are key players in neural
stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARgamma ligand,
increases PPARbeta/delta level, suggesting a possible cooperation between these
two PPARs in the control of cell fate behavior. Our work contributes to the
understanding of the molecular mechanisms associated to neural cell fate decision
and places PPARbeta/delta and PPARgamma as interesting new targets of modulation
of mammalian brain homeostasis.
PMID- 25852475
TI - Identification and characterization of mouse otic sensory lineage genes.
AB - Vertebrate embryogenesis gives rise to all cell types of an organism through the
development of many unique lineages derived from the three primordial germ
layers. The otic sensory lineage arises from the otic vesicle, a structure formed
through invagination of placodal non-neural ectoderm. This developmental lineage
possesses unique differentiation potential, giving rise to otic sensory cell
populations including hair cells, supporting cells, and ganglion neurons of the
auditory and vestibular organs. Here we present a systematic approach to identify
transcriptional features that distinguish the otic sensory lineage (from early
otic progenitors to otic sensory populations) from other major lineages of
vertebrate development. We used a microarray approach to analyze otic sensory
lineage populations including microdissected otic vesicles (embryonic day 10.5)
as well as isolated neonatal cochlear hair cells and supporting cells at
postnatal day 3. Non-otic tissue samples including periotic tissues and whole
embryos with otic regions removed were used as reference populations to evaluate
otic specificity. Otic populations shared transcriptome-wide correlations in
expression profiles that distinguish members of this lineage from non-otic
populations. We further analyzed the microarray data using comparative and
dimension reduction methods to identify individual genes that are specifically
expressed in the otic sensory lineage. This analysis identified and ranked top
otic sensory lineage-specific transcripts including Fbxo2, Col9a2, and Oc90, and
additional novel otic lineage markers. To validate these results we performed
expression analysis on select genes using immunohistochemistry and in situ
hybridization. Fbxo2 showed the most striking pattern of specificity to the otic
sensory lineage, including robust expression in the early otic vesicle and
sustained expression in prosensory progenitors and auditory and vestibular hair
cells and supporting cells.
PMID- 25852476
TI - PKCepsilon and allopregnanolone: functional cross-talk at the GABAA receptor
level.
AB - Changes in GABAergic inhibition occur during physiological processes, during
response to drugs and in various pathologies. These changes can be achieved
through direct allosteric modifications at the gamma-amino butyric acid (GABA)
type A (GABAA) receptor protein level, or by altering the synthesis, trafficking
and stability of the receptor. Neurosteroids (NSs) and protein kinase C (PKC) are
potent modulators of GABAA receptors and their effects are presumably
intermingled, even though evidence for this hypothesis is only partially
explored. However, several PKC isoforms are able to phosphorylate the GABAA
receptor, producing different functional effects. We focused on the epsilon
isoform, that has been correlated to the sensitivity of the GABAA receptor to
allosteric modulators and whose expression may be regulated in peripheral sensory
neurons by NSs. The cross-talk between PKC-epsilon and NSs, leading to changes in
GABAA receptor functionality, is considered and discussed in this perspective.
PMID- 25852477
TI - Cellular targets for neuropeptide Y-mediated control of adult neurogenesis.
AB - Neuropeptides are emerging as key regulators of stem cell niche activities in
health and disease, both inside and outside the central nervous system (CNS).
Among them, neuropeptide Y (NPY), one of the most abundant neuropeptides both in
the nervous system and in non-neural districts, has become the focus of much
attention for its involvement in a wide range of physiological and pathological
conditions, including the modulation of different stem cell activities. In
particular, a pro-neurogenic role of NPY has been evidenced in the neurogenic
niche, where a direct effect on neural progenitors has been demonstrated, while
different cellular types, including astrocytes, microglia and endothelial cells,
also appear to be responsive to the peptide. The marked modulation of the NPY
system during several pathological conditions that affect neurogenesis, including
stress, seizures and neurodegeneration, further highlights the relevance of this
peptide in the regulation of adult neurogenesis. In view of the considerable
interest in understanding the mechanisms controlling neural cell fate, this
review aims to summarize and discuss current data on NPY signaling in the
different cellular components of the neurogenic niche in order to elucidate the
complexity of the mechanisms underlying the modulatory properties of this
peptide.
PMID- 25852479
TI - Differential temporal expression of S100beta in developing rat brain.
AB - Radial glial cells (RGs) originally considered to provide scaffold to the
radially migrating neurons constitute a heterogeneous population of the
regionally variable precursor cells that generate both neurons as well as glia
depending upon the location and the timing of development. Hence specific
immunohistochemical markers are required to specify their spatiotemporal location
and fate in the neurogenic and gliogenic zones. We hypothesize S100beta as a
potential and unified marker for both primary and secondary progenitors. To
achieve this, cryocut sections from rat brains of varied embryonic and postnatal
ages were immunolabeled with a combination of antibodies, i.e., S100beta +
Nestin, Nestin + GFAP and S100beta + GFAP. A large population of the primary and
secondary progenitors, lining the VZ and SVZ, simultaneously co-expressed
S100beta and nestin establishing their progenitor nature. A downregulation of
both S100beta and nestin noticed by the end of the 1st postnatal week marks their
differentiation towards neuronal or glial lineage. In view of the absence of co
expression of GFAP (glial fibrillary acidic protein) either with S100beta or
nestin, the suitability of accepting GFAP as an early marker of RG's was
eliminated. Thus the dynamic expression of S100beta in both the neural stem cells
(NSCs) and RGs during embryonic and early neonatal life is associated with its
proliferative potential and migration of undifferentiated neuroblasts and
astrocytes. Once they lose their potential for proliferation, the S100beta
expression is repressed with its reemergence in mature astrocytes. This study
provides the first clear evidence of S100beta expression throughout the period of
neurogenesis and early gliogenesis, suggesting its suitability as a radial
progenitor cell marker.
PMID- 25852478
TI - Cancer as a channelopathy: ion channels and pumps in tumor development and
progression.
AB - Increasing evidence suggests that ion channels and pumps not only regulate
membrane potential, ion homeostasis, and electric signaling in excitable cells
but also play important roles in cell proliferation, migration, apoptosis and
differentiation. Consistent with a role in cell signaling, channel proteins and
ion pumps can form macromolecular complexes with growth factors, and cell
adhesion and other signaling molecules. And while cancer is still not being
cataloged as a channelopathy, as the non-traditional roles of ion pumps and
channels are being recognized, it is increasingly being suggested that ion
channels and ion pumps contribute to cancer progression. Cancer cell migration
requires the regulation of adhesion complexes between migrating cells and
surrounding extracellular matrix (ECM) proteins. Cell movement along solid
surfaces requires a sequence of cell protrusions and retractions that mainly
depend on regulation of the actin cytoskeleton along with contribution of
microtubules and molecular motor proteins such as mysoin. This process is
triggered and modulated by a combination of environmental signals, which are
sensed and integrated by membrane receptors, including integrins and cadherins.
Membrane receptors transduce these signals into downstream signaling pathways,
often involving the Rho GTPase protein family. These pathways regulate the
cytoskeletal rearrangements necessary for proper timing of adhesion, contraction
and detachment of cells in order to find their way through extracellular spaces.
Migration and adhesion involve continuous modulation of cell motility, shape and
volume, in which ion channels and pumps play major roles. Research on cancer
cells suggests that certain ion channels may be involved in aberrant tumor growth
and channel inhibitors often lead to growth arrest. This review will describe
recent research into the role of ion pumps and ion channels in cell migration and
adhesion, and how they may contribute to tumor development.
PMID- 25852480
TI - An epigenetic hypothesis for the genomic memory of pain.
AB - Chronic pain is accompanied with long-term sensory, affective and cognitive
disturbances. What are the mechanisms that mediate the long-term consequences of
painful experiences and embed them in the genome? We hypothesize that alterations
in DNA methylation, an enzymatic covalent modification of cytosine bases in DNA,
serve as a "genomic" memory of pain in the adult cortex. DNA methylation is an
epigenetic mechanism for long-term regulation of gene expression. Neuronal
plasticity at the neuroanatomical, functional, morphological, physiological and
molecular levels has been demonstrated throughout the neuroaxis in response to
persistent pain, including in the adult prefrontal cortex (PFC). We have
previously reported widespread changes in gene expression and DNA methylation in
the PFC many months following peripheral nerve injury. In support of this
hypothesis, we show here that up-regulation of a gene involved with synaptic
function, Synaptotagmin II (syt2), in the PFC in a chronic pain model is
associated with long-term changes in DNA methylation. The challenges of
understanding the contributions of epigenetic mechanisms such as DNA methylation
within the PFC to pain chronicity and their therapeutic implications are
discussed.
PMID- 25852481
TI - Differential modulation of repetitive firing and synchronous network activity in
neocortical interneurons by inhibition of A-type K(+) channels and Ih.
AB - GABAergic interneurons provide the main source of inhibition in the neocortex and
are important in regulating neocortical network activity. In the presence 4
aminopyridine (4-AP), CNQX, and D-APV, large amplitude GABAA-receptor mediated
depolarizing responses were observed in the neocortex. GABAergic networks are
comprised of several types of interneurons, each with its own protein expression
pattern, firing properties, and inhibitory role in network activity. Voltage
gated ion channels, especially A-type K(+) channels, differentially regulate
passive membrane properties, action potential (AP) waveform, and repetitive
firing properties in interneurons depending on their composition and
localization. HCN channels are known modulators of pyramidal cell intrinsic
excitability and excitatory network activity. Little information is available
regarding how HCN channels functionally modulate excitability of individual
interneurons and inhibitory networks. In this study, we examined the effect of 4
AP on intrinsic excitability of fast-spiking basket cells (FS-BCs) and Martinotti
cells (MCs). 4-AP increased the duration of APs in both FS-BCs and MCs. The
repetitive firing properties of MCs were differentially affected compared to FS
BCs. We also examined the effect of Ih inhibition on synchronous GABAergic
depolarizations and synaptic integration of depolarizing IPSPs. ZD 7288 enhanced
the amplitude and area of evoked GABAergic responses in both cell types.
Similarly, the frequency and area of spontaneous GABAergic depolarizations in
both FS-BCs and MCs were increased in presence of ZD 7288. Synaptic integration
of IPSPs in MCs was significantly enhanced, but remained unaltered in FS-BCs.
These results indicate that 4-AP differentially alters the firing properties of
interneurons, suggesting MCs and FS-BCs may have unique roles in GABAergic
network synchronization. Enhancement of GABAergic network synchronization by ZD
7288 suggests that HCN channels attenuate inhibitory network activity.
PMID- 25852483
TI - Dendritic patch-clamp recordings from cerebellar granule cells demonstrate
electrotonic compactness.
AB - Cerebellar granule cells (GCs), the smallest neurons in the brain, have on
average four short dendrites that receive high-frequency mossy fiber inputs
conveying sensory information. The short length of the dendrites suggests that
GCs are electrotonically compact allowing unfiltered integration of dendritic
inputs. The small average diameter of the dendrites (~0.7 um), however, argues
for dendritic filtering. Previous studies based on somatic recordings and
modeling indicated that GCs are electrotonically extremely compact. Here, we
performed patch-clamp recordings from GC dendrites in acute brain slices of mice
to directly analyze the electrotonic properties of GCs. Strikingly, the input
resistance did not differ significantly between dendrites and somata of GCs.
Furthermore, spontaneous excitatory postsynaptic potentials (EPSP) were similar
in amplitude at dendritic and somatic recording sites. From the dendritic and
somatic input resistances we determined parameters characterizing the
electrotonic compactness of GCs. These data directly demonstrate that cerebellar
GCs are electrotonically compact and thus ideally suited for efficient high
frequency information transfer.
PMID- 25852484
TI - Shank3-mutant mice lacking exon 9 show altered excitation/inhibition balance,
enhanced rearing, and spatial memory deficit.
AB - Shank3 is a postsynaptic scaffolding protein implicated in synapse development
and autism spectrum disorders. The Shank3 gene is known to produce diverse splice
variants whose functions have not been fully explored. In the present study, we
generated mice lacking Shank3 exon 9 (Shank3 (Delta9) mice), and thus missing
five out of 10 known Shank3 splice variants containing the N-terminal ankyrin
repeat region, including the longest splice variant, Shank3a. Our X-gal staining
results revealed that Shank3 proteins encoded by exon 9-containing splice
variants are abundant in upper cortical layers, striatum, hippocampus, and
thalamus, but not in the olfactory bulb or cerebellum, despite the significant
Shank3 mRNA levels in these regions. The hippocampal CA1 region of Shank3
(Delta9) mice exhibited reduced excitatory transmission at Schaffer collateral
synapses and increased frequency of spontaneous inhibitory synaptic events in
pyramidal neurons. In contrast, prelimbic layer 2/3 pyramidal neurons in the
medial prefrontal cortex displayed decreased frequency of spontaneous inhibitory
synaptic events, indicating alterations in the ratio of excitation/inhibition
(E/I ratio) in the Shank3 (Delta9) brain. These mice displayed a mild increase in
rearing in a novel environment and mildly impaired spatial memory, but showed
normal social interaction and repetitive behavior. These results suggest that
ankyrin repeat-containing Shank3 splice variants are important for E/I balance,
rearing behavior, and spatial memory.
PMID- 25852482
TI - Researching glutamate - induced cytotoxicity in different cell lines: a
comparative/collective analysis/study.
AB - Although glutamate is one of the most important excitatory neurotransmitters of
the central nervous system, its excessive extracellular concentration leads to
uncontrolled continuous depolarization of neurons, a toxic process called,
excitotoxicity. In excitotoxicity glutamate triggers the rise of intracellular
Ca(2+) levels, followed by up regulation of nNOS, dysfunction of mitochondria,
ROS production, ER stress, and release of lysosomal enzymes. Excessive calcium
concentration is the key mediator of glutamate toxicity through over activation
of ionotropic and metabotropic receptors. In addition, glutamate accumulation can
also inhibit cystine (CySS) uptake by reversing the action of the CySS/glutamate
antiporter. Reversal of the antiporter action reinforces the aforementioned
events by depleting neurons of cysteine and eventually glutathione's reducing
potential. Various cell lines have been employed in the pursuit to understand the
mechanism(s) by which excitotoxicity affects the cells leading them ultimately to
their demise. In some cell lines glutamate toxicity is exerted mainly through
over activation of NMDA, AMPA, or kainate receptors whereas in other cell lines
lacking such receptors, the toxicity is due to glutamate induced oxidative
stress. However, in the greatest majority of the cell lines ionotropic glutamate
receptors are present, co-existing to CySS/glutamate antiporters and metabotropic
glutamate receptors, supporting the assumption that excitotoxicity effect in
these cells is accumulative. Different cell lines differ in their responses when
exposed to glutamate. In this review article the responses of PC12, SH-SY5Y, HT
22, NT-2, OLCs, C6, primary rat cortical neurons, RGC-5, and SCN2.2 cell systems
are systematically collected and analyzed.
PMID- 25852485
TI - Imbalance of excitation and inhibition at threshold level in the auditory cortex.
AB - The interplay of cortical excitation and inhibition is a fundamental feature of
cortical information processing. Excitation and inhibition in single cortical
neurons are balanced in their response to optimal sensory stimulation due to
thalamocortical feedforward microcircuitry. It is unclear whether the balance
between cortical excitation and inhibition is maintained at the threshold
stimulus level. Using in vivo whole-cell patch-clamp recording of thalamocortical
recipient neurons in the primary auditory cortex of mice, we examined the tone
evoked excitatory and inhibitory postsynaptic currents at threshold levels.
Similar to previous reports, tone induced excitatory postsynaptic currents when
the membrane potentials were held at 70 mV and inhibitory postsynaptic currents
when the membrane potentials were held at 0 mV on single cortical neurons. This
coupled excitation and inhibition is not demonstrated when threshold-level tone
stimuli are presented. In most cases, tone induced only excitatory postsynaptic
current. The best frequencies of excitatory and inhibitory responses were often
different and thresholds of inhibitory responses were mostly higher than those of
excitatory responses. Our data suggest that the excitatory and inhibitory inputs
to single cortical neurons are imbalanced at the threshold level. This imbalance
may result from the inherent dynamics of thalamocortical feedforward
microcircuitry.
PMID- 25852486
TI - Glycine and GABAA receptors mediate tonic and phasic inhibitory processes that
contribute to prepulse inhibition in the goldfish startle network.
AB - Prepulse inhibition (PPI) is understood as a sensorimotor gating process that
attenuates sensory flow to the startle pathway during early stages (20-1000 ms)
of information processing. Here, we applied in vivo electrophysiology and
pharmacology to determine if PPI is mediated by glycine receptors (GlyRs) and/or
GABAA receptors (GABAARs) in the goldfish auditory startle circuit. Specifically,
we used selective antagonists to dissect the contributions of target receptors on
sound-evoked postsynaptic potentials (PSPs) recorded in the neurons that initiate
startle, the Mauthner-cells (M-cell). We found that strychnine, a GlyR
antagonist, disrupted a fast-activated (5 ms) and rapidly (<50 ms) decaying (feed
forward) inhibitory process that contributes to PPI at 20 ms prepulse/pulse inter
stimulus intervals (ISI). Additionally we observed increases of the evoked
postsynaptic potential (PSP) peak amplitude (+87.43 +/- 21.53%, N = 9) and
duration (+204 +/- 48.91%, N = 9). In contrast, treatment with bicuculline, a
GABAAR antagonist, caused a general reduction in PPI across all tested
interstimulus intervals (ISIs) (20-500 ms). Bicuculline also increased PSP peak
amplitude (+133.8 +/- 10.3%, N = 5) and PSP duration (+284.95 +/- 65.64%, N = 5).
Treatment with either antagonist also tonically increased post-synaptic
excitability in the M-cells, reflected by an increase in the magnitude of
antidromically-evoked action potentials (APs) by 15.07 +/- 3.21%, N = 7 and 16.23
+/- 7.08%, N = 5 for strychnine and bicuculline, respectively. These results
suggest that GABAARs and GlyRs are functionally segregated to short- and longer
lasting sound-evoked (phasic) inhibitory processes that contribute to PPI, with
the mediation of tonic inhibition by both receptor systems being critical for
gain control within the M-cell startle circuit.
PMID- 25852487
TI - Exciting times for inhibition: GABAergic synaptic transmission in dentate gyrus
interneuron networks.
PMID- 25852488
TI - Localization of mutant ubiquitin in the brain of a transgenic mouse line with
proteasomal inhibition and its validation at specific sites in Alzheimer's
disease.
AB - Loss of protein quality control by the ubiquitin-proteasome system (UPS) during
aging is one of the processes putatively contributing to cellular stress and
Alzheimer's disease (AD) pathogenesis. Recently, pooled Genome Wide Association
Studies (GWAS), pathway analysis and proteomics identified protein ubiquitination
as one of the key modulators of AD. Mutations in ubiquitin B mRNA that result in
UBB(+1) dose-dependently cause an impaired UPS, subsequent accumulation of
UBB(+1) and most probably depositions of other aberrant proteins present in
plaques and neurofibrillary tangles. We used specific immunohistochemical probes
for a comprehensive topographic mapping of the UBB(+1) distribution in the brains
of transgenic mouse line 3413 overexpressing UBB(+1). We also mapped the
expression of UBB(+1) in brain areas of AD patients selected based upon the
distribution of UBB(+1) in line 3413. Therefore, we focused on the olfactory
bulb, basal ganglia, nucleus basalis of Meynert, inferior colliculus and raphe
nuclei. UBB(+1) distribution was compared with established probes for pre-tangles
and tangles and Abeta plaques. UBB(+1) distribution found in line 3413 is partly
mirrored in the AD brain. Specifically, nuclei with substantial accumulations of
tangle-bearing neurons, such as the nucleus basalis of Meynert and raphe nuclei
also present high densities of UBB(+1) positive tangles. Line 3413 is useful for
studying the contribution of proteasomal dysfunction in AD. The findings are
consistent with evidence that areas outside the forebrain are also affected in
AD. Line 3413 may also be predictive for other conformational diseases, including
related tauopathies and polyglutamine diseases, in which UBB(+1) accumulates in
their cellular hallmarks.
PMID- 25852489
TI - A new scenario of hypothalamic organization: rationale of new hypotheses
introduced in the updated prosomeric model.
AB - In this essay, we aim to explore in depth the new concept of the hypothalamus
that was presented in the updated prosomeric model (Puelles et al., 2012b; Allen
Developing Mouse Brain Atlas). Initial sections deal with the antecedents of
prosomeric ideas represented by the extensive literature centered on the
alternative columnar model of Herrick (1910), Kuhlenbeck (1973) and Swanson
(1992, 2003); a detailed critique explores why the columnar model is not helpful
in the search for causal developmental explanations. In contrast, the emerging
prosomeric scenario visibly includes many possibilities to propose causal
explanations of hypothalamic structure relative to both anteroposterior and
dorsoventral patterning mechanisms, and insures the possibility to compare
hypothalamic histogenesis with that of more caudal parts of the brain. Next the
four major changes introduced in the organization of the hypothalamus on occasion
of the updated model are presented, and our rationale for these changes is
explored in detail. It is hoped that this example of morphological theoretical
analysis may be useful for readers interested in brain models, or in
understanding why models may need to change in the quest for higher consistency.
PMID- 25852490
TI - Synaptic connectivity of the cholinergic axons in the olfactory bulb of the
cynomolgus monkey.
AB - The olfactory bulb (OB) of mammals receives cholinergic afferents from the
horizontal limb of the diagonal band of Broca (HDB). At present, the synaptic
connectivity of the cholinergic axons on the circuits of the OB has only been
investigated in the rat. In this report, we analyze the synaptic connectivity of
the cholinergic axons in the OB of the cynomolgus monkey (Macaca fascicularis).
Our aim is to investigate whether the cholinergic innervation of the bulbar
circuits is phylogenetically conserved between macrosmatic and microsmatic
mammals. Our results demonstrate that the cholinergic axons form synaptic
contacts on interneurons. In the glomerular layer, their main targets are the
periglomerular cells, which receive axo-somatic and axo-dendritic synapses. In
the inframitral region, their main targets are the granule cells, which receive
synaptic contacts on their dendritic shafts and spines. Although the cholinergic
boutons were frequently found in close vicinity of the dendrites of principal
cells, we have not found synaptic contacts on them. From a comparative
perspective, our data indicate that the synaptic connectivity of the cholinergic
circuits is highly preserved in the OB of macrosmatic and microsmatic mammals.
PMID- 25852492
TI - The nasal cavity and its olfactory sensory territories.
PMID- 25852491
TI - Cadherins mediate sequential roles through a hierarchy of mechanisms in the
developing mammillary body.
AB - Expression of intricate combinations of cadherins (a family of adhesive membrane
proteins) is common in the developing central nervous system. On this basis, a
combinatorial cadherin code has long been proposed to underlie neuronal sorting
and to be ultimately responsible for the layers, columns and nuclei of the brain.
However, experimental proof of this particular function of cadherins has proven
difficult to obtain and the question is still not clear. Alternatively, non
specific, non-combinatorial, purely quantitative adhesive differentials have been
proposed to explain neuronal sorting in the brain. Do cadherin combinations
underlie brain cytoarchitecture? We approached this question using as model a
well-defined forebrain nucleus, the mammillary body (MBO), which shows strong,
homogeneous expression of one single cadherin (Cdh11) and patterned,
combinatorial expression of Cdh6, -8 and -10. We found that, besides the known
combinatorial Cdh pattern, MBO cells are organized into a second, non-overlapping
pattern grouping neurons with the same date of neurogenesis. We report that, in
the Foxb1 mouse mutant, Cdh11 expression fails to be maintained during MBO
development. This disrupted the combination-based as well as the birthdate-based
sorting in the mutant MBO. In utero RNA interference (RNAi) experiments knocking
down Cdh11 in MBO-fated migrating neurons at one specific age showed that Cdh11
expression is required for chronological entrance in the MBO. Our results suggest
that neuronal sorting in the developing MBO is caused by adhesion-based, non
combinatorial mechanisms that keep neurons sorted according to birthdate
information (possibly matching them to target neurons chronologically sorted in
the same manner). Non-specific adhesion mechanisms would also prevent cadherin
combinations from altering the birthdate-based sorting. Cadherin combinations
would presumably act later to support specific synaptogenesis through specific
axonal fasciculation and final target recognition.
PMID- 25852493
TI - Acute oral administration of low doses of methylphenidate targets calretinin
neurons in the rat septal area.
AB - Methylphenidate (MPD) is a commonly administered drug to treat children suffering
from attention deficit hyperactivity disorder (ADHD). Alterations in septal
driven hippocampal theta rhythm may underlie attention deficits observed in these
patients. Amongst others, the septo-hippocampal connections have long been
acknowledged to be important in preserving hippocampal function. Thus, we wanted
to ascertain if MPD administration, which improves attention in patients, could
affect septal areas connecting with hippocampus. We used low and orally
administered MPD doses (1.3, 2.7 and 5 mg/Kg) to rats what mimics the dosage
range in humans. In our model, we observed no effect when using 1.3 mg/Kg MPD;
whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression
specifically in the medial septum (MS), an area intimately connected to the
hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and
striatum, and found that only 5 mg/Kg induced c-fos levels increase. In these
areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the MS
the sparse tyrosine hydroxylase fibers did not overlap with c-fos positive
neurons. Double immunofluorescence of c-fos with neuronal markers in the septal
area revealed that co-localization with choline acethyl transferase, parvalbumin,
and calbindin with c-fos did not change with MPD treatment; whereas, calretinin
and c-fos double labeled neurons increased after MPD administration. Altogether,
these results suggest that low and acute doses of methylphenidate primary target
specific populations of caltretinin medial septal neurons.
PMID- 25852494
TI - Remotely-supervised transcranial direct current stimulation (tDCS) for clinical
trials: guidelines for technology and protocols.
AB - The effect of transcranial direct current stimulation (tDCS) is cumulative.
Treatment protocols typically require multiple consecutive sessions spanning
weeks or months. However, traveling to clinic for a tDCS session can present an
obstacle to subjects and their caregivers. With modified devices and headgear,
tDCS treatment can be administered remotely under clinical supervision,
potentially enhancing recruitment, throughput, and convenience. Here we propose
standards and protocols for clinical trials utilizing remotely-supervised tDCS
with the goal of providing safe, reproducible and well-tolerated stimulation
therapy outside of the clinic. The recommendations include: (1) training of staff
in tDCS treatment and supervision; (2) assessment of the user's capability to
participate in tDCS remotely; (3) ongoing training procedures and materials
including assessments of the user and/or caregiver; (4) simple and fail-safe
electrode preparation techniques and tDCS headgear; (5) strict dose control for
each session; (6) ongoing monitoring to quantify compliance (device preparation,
electrode saturation/placement, stimulation protocol), with corresponding
corrective steps as required; (7) monitoring for treatment-emergent adverse
effects; (8) guidelines for discontinuation of a session and/or study
participation including emergency failsafe procedures tailored to the treatment
population's level of need. These guidelines are intended to provide a minimal
level of methodological rigor for clinical trials seeking to apply tDCS outside a
specialized treatment center. We outline indication-specific applications
(Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis,
Palliative Care) following these recommendations that support a standardized
framework for evaluating the tolerability and reproducibility of remote
supervised tDCS that, once established, will allow for translation of tDCS
clinical trials to a greater size and range of patient populations.
PMID- 25852495
TI - Modulating pathological oscillations by rhythmic non-invasive brain stimulation-a
therapeutic concept?
AB - A large amount of studies of the last decades revealed an association between
human behavior and oscillatory activity in the human brain. Alike, abnormalities
of oscillatory activity were related with pathological behavior in many
neuropsychiatric disorders, such as in Parkinson's disease (PD) or in
schizophrenia (SCZ). As a therapeutic tool, non-invasive brain stimulation (NIBS)
has demonstrated the potential to improve behavioral performance in patients
suffering from neuropsychiatric disorders. Since evidence accumulates that NIBS
might be able to modulate oscillatory activity and related behavior in a
scientific setting, this review focuses on discussing potential interventional
strategies to target abnormalities in oscillatory activity in neuropsychiatric
disorders. In particular, we will review oscillatory changes described in
patients after stroke, with PD or suffering from SCZ. Potential ways of targeting
interventionally the underlying pathological oscillations to improve related
pathological behavior will be further discussed.
PMID- 25852497
TI - A new measure for the revised reinforcement sensitivity theory: psychometric
criteria and genetic validation.
AB - Jeffrey Gray's Reinforcement Sensitivity Theory (RST) represents one of the most
influential biologically-based personality theories describing individual
differences in approach and avoidance tendencies. The most prominent self-report
inventory to measure individual differences in approach and avoidance behavior to
date is the BIS/BAS scale by Carver and White (1994). As Gray and McNaughton
(2000) revised the RST after its initial formulation in the 1970/80s, and given
the Carver and White measure is based on the initial conceptualization of RST,
there is a growing need for self-report inventories measuring individual
differences in the revised behavioral inhibition system (BIS), behavioral
activation system (BAS) and the fight, flight, freezing system (FFFS). Therefore,
in this paper we present a new questionnaire measuring individual differences in
the revised constructs of the BIS, BAS and FFFS in N = 1814 participants (German
sample). An English translated version of the new measure is also presented and
tested in N = 299 English language participants. A large number of German
participants (N = 1090) also filled in the BIS/BAS scales by Carver and White
(1994) and the correlations between these measures are presented. Finally, this
same subgroup of participants provided buccal swaps for the investigation of the
arginine vasopressin receptor 1a (AVPR1a) gene. Here, a functional genetic
polymorphism (rs11174811) on the AVPR1a gene was shown to be associated with
individual differences in both the revised BIS and classic BIS dimensions.
PMID- 25852498
TI - The cognitive thalamus.
PMID- 25852496
TI - Theta variation and spatiotemporal scaling along the septotemporal axis of the
hippocampus.
AB - Hippocampal theta has been related to locomotor speed, attention, anxiety,
sensorimotor integration and memory among other emergent phenomena. One
difficulty in understanding the function of theta is that the hippocampus (HPC)
modulates voluntary behavior at the same time that it processes sensory input.
Both functions are correlated with characteristic changes in theta indices. The
current review highlights a series of studies examining theta local field
potential (LFP) signals across the septotemporal or longitudinal axis of the HPC.
While the theta signal is coherent throughout the entirety of the HPC, the
amplitude, but not the frequency, of theta varies significantly across its three
dimensional expanse. We suggest that the theta signal offers a rich vein of
information about how distributed neuronal ensembles support emergent function.
Further, we speculate that emergent function across the long axis varies with
respect to spatiotemporal scale. Thus, septal HPC processes details of the
proximal spatiotemporal environment while more temporal aspects process larger
spaces and wider time-scales. The degree to which emergent functions are
supported by the synchronization of theta across the septotemporal axis is an
open question. Our working model is that theta synchrony serves to bind ensembles
representing varying resolutions of spatiotemporal information at interdependent
septotemporal areas of the HPC. Such synchrony and cooperative interactions along
the septotemporal axis likely support memory formation and subsequent
consolidation and retrieval.
PMID- 25852499
TI - A pavlovian model of the amygdala and its influence within the medial temporal
lobe.
AB - Recent advances in neuroscience give us a better view of the inner structure of
the amygdala, of its relations with other regions in the Medial Temporal Lobe
(MTL) and of the prominent role of neuromodulation. They have particularly shed
light on two kinds of neurons in the basal nucleus of the amygdala, the so-called
fear neurons and extinction neurons. Fear neurons mediate context-dependent fear
by receiving contextual information from the hippocampus, whereas extinction
neurons are linked with the medial prefrontal cortex (mPFC) and involved in fear
extinction. The computational model of the amygdala that we describe in this
paper is primarily a model of pavlovian conditioning, but its architecture also
emphasizes the central role of the amygdala in the MTL memory processes through
three main information flows. (i) Thalamic and higher order sensory cortical
inputs including from the perirhinal cortex are received in the lateral amygdalar
nucleus, where CS-US associations can be acquired. (ii) These associations are
subsequently modulated, in the basal nucleus of the amygdala, by contextual
inputs coming from the hippocampus and the mPFC. Basal fear and extinction
neurons indicate the currently valid association to their main targets including
in the MTL and the mPFC. (iii) The competition for the choice of the pavlovian
response is ultimately performed by projection of these amygdalar neurons in the
central nucleus of the amygdala where, beyond motor responding, a hormonal
response, including cholinergic modulation, is also triggered via the basal
forebrain. In turn, acetylcholine modulates activation in the basal nucleus and
facilitates learning in the hippocampus. Based on biologically founded arguments,
our model replicates a number of biological experiments, proposes some
predictions about the role of amygdalar regions and describes pavlovian
conditioning as a distributed systemic learning, binding memory processes in the
MTL.
PMID- 25852501
TI - Editorial for research topic "Autism: the movement perspective".
PMID- 25852500
TI - Individual differences in approach-avoidance aptitude: some clues from research
on Parkinson's disease.
AB - Approach and avoidance are two basic behavioral aptitudes of humans whose correct
balance is critical for successful adaptation to the environment. As the
expression of approach and avoidance tendencies may differ significantly between
healthy individuals, different psychobiological factors have been posited to
account for such variability. In this regard, two main issues are still open that
refers to (i) the role played by dopamine neurotransmission; and (ii) the
possible influence of cognitive characteristics, particularly executive
functioning. The aim of the present paper was to highlight the contribution of
research on Parkinson's disease (PD) to our understanding of the above issues. In
particular, we here reviewed PD literature to clarify whether neurobiological and
neuropsychological modifications due to PD are associated to changes in approach
avoidance related personality features. Available data indicate that PD patients
may show and approach-avoidance imbalance as documented by lower novelty-seeking
and higher harm-avoidance behaviors, possibly suggesting a relationship with
neurobiological and neurocognitive PD-related changes. However, the literature
that directly investigated this issue is still sparse and much more work is
needed to better clarify it.
PMID- 25852503
TI - Commentary on: An exploration of sensory and movement differences from the
perspective of individuals with autism.
PMID- 25852502
TI - The addicted brain: understanding the neurophysiological mechanisms of addictive
disorders.
PMID- 25852504
TI - Neuromodulation and the mind-brain relation.
PMID- 25852505
TI - Perception of biological motion from size-invariant body representations.
AB - The visual recognition of action is one of the socially most important and
computationally demanding capacities of the human visual system. It combines
visual shape recognition with complex non-rigid motion perception. Action
presented as a point-light animation is a striking visual experience for anyone
who sees it for the first time. Information about the shape and posture of the
human body is sparse in point-light animations, but it is essential for action
recognition. In the posturo-temporal filter model of biological motion perception
posture information is picked up by visual neurons tuned to the form of the human
body before body motion is calculated. We tested whether point-light stimuli are
processed through posture recognition of the human body form by using a typical
feature of form recognition, namely size invariance. We constructed a point-light
stimulus that can only be perceived through a size-invariant mechanism. This
stimulus changes rapidly in size from one image to the next. It thus disrupts
continuity of early visuo-spatial properties but maintains continuity of the body
posture representation. Despite this massive manipulation at the visuo-spatial
level, size-changing point-light figures are spontaneously recognized by naive
observers, and support discrimination of human body motion.
PMID- 25852506
TI - Impact of an additional chronic BDNF reduction on learning performance in an
Alzheimer mouse model.
AB - There is increasing evidence that brain-derived neurotrophic factor (BDNF) plays
a crucial role in Alzheimer's disease (AD) pathology. A number of studies
demonstrated that AD patients exhibit reduced BDNF levels in the brain and the
blood serum, and in addition, several animal-based studies indicated a potential
protective effect of BDNF against Abeta-induced neurotoxicity. In order to
further investigate the role of BDNF in the etiology of AD, we created a novel
mouse model by crossing a well-established AD mouse model (APP/PS1) with a mouse
exhibiting a chronic BDNF deficiency (BDNF(+/-)). This new triple transgenic
mouse model enabled us to further analyze the role of BDNF in AD in vivo. We
reasoned that in case BDNF has a protective effect against AD pathology, an AD
like phenotype in our new mouse model should occur earlier and/or in more
severity than in the APP/PS1-mice. Indeed, the behavioral analysis revealed that
the APP/PS1-BDNF(+/-)-mice show an earlier onset of learning impairments in a two
way active avoidance task in comparison to APP/PS1- and BDNF(+/-)-mice. However
in the Morris water maze (MWM) test, we could not observe an overall aggrevated
impairment in spatial learning and also short-term memory in an object
recognition task remained intact in all tested mouse lines. In addition to the
behavioral experiments, we analyzed the amyloid plaque pathology in the APP/PS1
and APP/PS1-BDNF(+/-)-mice and observed a comparable plaque density in the two
genotypes. Moreover, our results revealed a higher plaque density in prefrontal
cortical compared to hippocampal brain regions. Our data reveal that higher
cognitive tasks requiring the recruitment of cortical networks appear to be more
severely affected in our new mouse model than learning tasks requiring mainly sub
cortical networks. Furthermore, our observations of an accelerated impairment in
active avoidance learning in APP/PS1-BDNF(+/-)-mice further supports the
hypothesis that BDNF deficiency amplifies AD-related cognitive dysfunctions.
PMID- 25852507
TI - The alteration of gray matter volume and cognitive control in adolescents with
internet gaming disorder.
AB - OBJECTIVE: Internet gaming disorder (IGD) has been investigated by many
behavioral and neuroimaging studies, for it has became one of the main behavior
disorders among adolescents. However, few studies focused on the relationship
between alteration of gray matter volume (GMV) and cognitive control feature in
IGD adolescents. METHODS: Twenty-eight participants with IAD and twenty-eight
healthy age and gender matched controls participated in the study. Brain
morphology of adolescents with IGD and healthy controls was investigated using an
optimized voxel-based morphometry (VBM) technique. Cognitive control performances
were measured by Stroop task, and correlation analysis was performed between
brain structural change and behavioral performance in IGD group. RESULTS: The
results showed that GMV of the bilateral anterior cingulate cortex (ACC),
precuneus, supplementary motor area (SMA), superior parietal cortex, left dorsal
lateral prefrontal cortex (DLPFC), left insula, and bilateral cerebellum
decreased in the IGD participants compared with healthy controls. Moreover, GMV
of the ACC was negatively correlated with the incongruent response errors of
Stroop task in IGD group. CONCLUSION: Our results suggest that the alteration of
GMV is associated with the performance change of cognitive control in adolescents
with IGD, which indicating substantial brain image effects induced by IGD.
PMID- 25852508
TI - Glycogen synthase kinase-3beta inhibition in the medial prefrontal cortex
mediates paradoxical amphetamine action in a mouse model of ADHD.
AB - Psychostimulants show therapeutic efficacy in the treatment of attention-deficit
hyperactivity disorder (ADHD). It is generally assumed that they ameliorate ADHD
symptoms via interfering with monoaminergic signaling. We combined behavioral
pharmacology, neurochemistry and molecular analyses to identify mechanisms
underlying the paradoxical calming effect of amphetamine in low trait anxiety
behavior (LAB) mice, a novel multigenetic animal model of ADHD. Amphetamine (1
mg/kg) and methylphenidate (10 mg/kg) elicited similar dopamine and
norepinephrine release in the medial prefrontal cortex (mPFC) and in the striatum
of LAB mice. In contrast, amphetamine decreased, while methylphenidate increased
locomotor activity. This argues against changes in dopamine and/or norepinephrine
release as mediators of amphetamine paradoxical effects. Instead, the calming
activity of amphetamine corresponded to the inhibition of glycogen synthase
kinase 3beta (GSK3beta) activity, specifically in the mPFC. Accordingly, not only
systemic administration of the GSK3beta inhibitor TDZD-8 (20 mg/kg), but also
local microinjections of TDZD-8 and amphetamine into the mPFC, but not into the
striatum, decreased locomotor activity in LAB mice. Amphetamine effects seem to
depend on NMDA receptor signaling, since pre- or co-treatment with MK-801 (0.3
mg/kg) abolished the effects of amphetamine (1 mg/kg) on the locomotion and on
the phosphorylation of GSK3beta at the level of the mPFC. Taken together, the
paradoxical calming effect of amphetamine in hyperactive LAB mice concurs with a
decreased GSK3beta activity in the mPFC. This effect appears to be independent of
dopamine or norepinephrine release, but contingent on NMDA receptor signaling.
PMID- 25852509
TI - Can electrical stimulation of the human bed nucleus of the stria terminalis
reduce contextual anxiety? An unanswered question.
PMID- 25852510
TI - Binding in working memory and frontal lobe in normal aging: is there any
similarity with autism?
AB - Some studies highlight similarities between Autism Spectrum Disorder (ASD) and
healthy aging. Indeed, the decline in older individuals' ability to create a
unified representation of the individual features of an event is thought to arise
from a disruption of binding within the episodic buffer of working memory (WM) as
the same way as observed in ASD. In both cases, this deficit may result from an
abnormal engagement of a frontohippocampal network. The objective of the present
study is to identify both cognitive processes and neural substrates associated
with the deficit of binding in WM in healthy aging. We studied the capacity of
binding and the cognitive processes that might subtend its decline in 72 healthy
participants aged 18-84 years. We examined the behavioral data in relation to the
changes in brain metabolism associated with the age-related decline in a subgroup
of 34 healthy participants aged 20-77 years using the resting-state [(18)F]
fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). Forward stepwise
regression analyses showed that the age-related decline in binding was partially
explained by a decline in inhibition and processing speed. PET correlation
analyses indicated that metabolism of the frontal regions, anterior and middle
cingulate cortices is implicated in this phenomenon. These data suggest that
executive functions and processing speed may play a crucial role in the capacity
to integrate unified representations in memory in aging. Possible implications
are discussed in ASD.
PMID- 25852511
TI - Altered baseline brain activity in experts measured by amplitude of low frequency
fluctuations (ALFF): a resting state fMRI study using expertise model of
acupuncturists.
AB - It is well established that expertise modulates evoked brain activity in response
to specific stimuli. Recently, researchers have begun to investigate how
expertise influences the resting brain. Among these studies, most focused on the
connectivity features within/across regions, i.e., connectivity
patterns/strength. However, little concern has been given to a more fundamental
issue whether or not expertise modulates baseline brain activity. We investigated
this question using amplitude of low-frequency (<0.08 Hz) fluctuation (ALFF) as
the metric of brain activity and a novel expertise model, i.e., acupuncturists,
due to their robust proficiency in tactile perception and emotion regulation.
After the psychophysical and behavioral expertise screening procedure, 23
acupuncturists and 23 matched non-acupuncturists (NA) were enrolled. Our results
explicated higher ALFF for acupuncturists in the left ventral medial prefrontal
cortex (VMPFC) and the contralateral hand representation of the primary
somatosensory area (SI) (corrected for multiple comparisons). Additionally, ALFF
of VMPFC was negatively correlated with the outcomes of the emotion regulation
task (corrected for multiple comparisons). We suggest that our study may reveal a
novel connection between the neuroplasticity mechanism and resting state
activity, which would upgrade our understanding of the central mechanism of
learning. Furthermore, by showing that expertise can affect the baseline brain
activity as indicated by ALFF, our findings may have profound implication for
functional neuroimaging studies especially those involving expert models, in that
difference in baseline brain activity may either smear the spatial pattern of
activations for task data or introduce biased results into connectivity-based
analysis for resting data.
PMID- 25852512
TI - Must analysis of meaning follow analysis of form? A time course analysis.
AB - Many models of word recognition assume that processing proceeds sequentially from
analysis of form to analysis of meaning. In the context of morphological
processing, this implies that morphemes are processed as units of form prior to
any influence of their meanings. Some interpret the apparent absence of
differences in recognition latencies to targets (SNEAK) in form and semantically
similar (sneaky-SNEAK) and in form similar and semantically dissimilar (sneaker
SNEAK) prime contexts at a stimulus onset asynchrony (SOA) of 48 ms as consistent
with this claim. To determine the time course over which degree of semantic
similarity between morphologically structured primes and their targets influences
recognition in the forward masked priming variant of the lexical decision
paradigm, we compared facilitation for the same targets after semantically
similar and dissimilar primes across a range of SOAs (34-100 ms). The effect of
shared semantics on recognition latency increased linearly with SOA when long
SOAs were intermixed (Experiments 1A and 1B) and latencies were significantly
faster after semantically similar than dissimilar primes at homogeneous SOAs of
48 ms (Experiment 2) and 34 ms (Experiment 3). Results limit the scope of form
then-semantics models of recognition and demonstrate that semantics influences
even the very early stages of recognition. Finally, once general performance
across trials has been accounted for, we fail to provide evidence for individual
differences in morphological processing that can be linked to measures of reading
proficiency.
PMID- 25852513
TI - Transcranial direct current stimulation modulates efficiency of reading
processes.
AB - Transcranial direct current stimulation (tDCS) is a neuromodulatory technique
that offers promise as an investigative method for understanding complex
cognitive operations such as reading. This study explores the ability of a single
session of tDCS to modulate reading efficiency and phonological processing
performance within a group of healthy adults. Half the group received anodal or
cathodal stimulation, on two separate days, of the left temporo-parietal junction
while the other half received anodal or cathodal stimulation of the right
homologue area. Pre- and post-stimulation assessment of reading efficiency and
phonological processing was carried out. A larger pre-post difference in reading
efficiency was found for participants who received right anodal stimulation
compared to participants who received left anodal stimulation. Further, there was
a significant post-stimulation increase in phonological processing speed
following right hemisphere anodal stimulation. Implications for models of reading
and reading impairment are discussed.
PMID- 25852514
TI - Similarity hypothesis: understanding of others with autism spectrum disorders by
individuals with autism spectrum disorders.
AB - Individuals with an autism spectrum disorder (ASD) are generally thought to lack
empathy. However, according to recent empirical and self-advocacy studies,
individuals with ASD identify with others with ASD. Based on mutual
understanding, individuals with ASD respond empathically to others with these
disorders. Results have shown that typically developing (TD) adults identify with
TD fictional characters, and that such identification plays a critical role in
social cognition. TD individuals retrieve episodes involving TD individuals
faster than they retrieve episodes involving ASD individuals. Individuals with
ASD also show a "similarity effect" whereby they retrieve stories involving ASD
individuals more effectively when the stories have consistent outcomes than when
they have inconsistent outcomes. In this context, I hypothesized that
similarities between a perceiver and a target facilitate cognitive processing.
This hypothesis was named the "similarity hypothesis". Perceivers empathize with
targets similar to themselves, which facilitates subsequent cognitive processing.
Behavioral and neuroimaging studies are reviewed based on the similarity
hypothesis.
PMID- 25852516
TI - Objective and personalized longitudinal assessment of a pregnant patient with
post severe brain trauma.
AB - BACKGROUND: Following severe trauma to the brain (whether internally generated by
seizures, tumors or externally caused by collision with or penetration of
objects) individuals may experience initial coma state followed by slow recovery
and rehabilitation treatment. At present there is no objective biometric to track
the daily progression of the person for extended periods of time. OBJECTIVE: We
introduce new analytical techniques to process data from physically wearable
sensors and help track the longitudinal progression of motions and physiological
states upon the brain trauma. Setting and Participant: The data used to
illustrate the methods were collected at the hospital settings from a pregnant
patient in coma state. The patient had brain trauma from a large debilitating
seizure due to a large tumor in the right pre-frontal lobe. MAIN MEASURES: We
registered the wrist motions and the surface-skin-temperature across several
daily sessions in four consecutive months. A new statistical technique is
introduced for personalized analyses of the rates of change of the stochastic
signatures of these patterns. RESULTS: We detected asymmetries in the wrists'
data that identified in the dominant limb critical points of change in
physiological and motor control states. These patterns could blindly identify the
time preceding the baby's delivery by C-section when the patient systematically
brought her hand to her abdominal area. Changes in temperature were sharp and
accompanied by systematic changes in the statistics of the motions that rendered
her dominant wrist's micro-movements more systematically reliable and predictable
than those of the non-dominant writst. CONCLUSIONS: The new analytics paired with
wearable sensing technology may help track the day-by-day individual progression
of a patient with post brain trauma in clinical settings and in the home
environment.
PMID- 25852515
TI - Solving the detour problem in navigation: a model of prefrontal and hippocampal
interactions.
AB - Adapting behavior to accommodate changes in the environment is an important
function of the nervous system. A universal problem for motile animals is the
discovery that a learned route is blocked and a detour is required. Given the
substantial neuroscience research on spatial navigation and decision-making it is
surprising that so little is known about how the brain solves the detour problem.
Here we review the limited number of relevant functional neuroimaging, single
unit recording and lesion studies. We find that while the prefrontal cortex (PFC)
consistently responds to detours, the hippocampus does not. Recent evidence
suggests the hippocampus tracks information about the future path distance to the
goal. Based on this evidence we postulate a conceptual model in which: Lateral
PFC provides a prediction error signal about the change in the path, frontopolar
and superior PFC support the re-formulation of the route plan as a novel subgoal
and the hippocampus simulates the new path. More data will be required to
validate this model and understand (1) how the system processes the different
options; and (2) deals with situations where a new path becomes available (i.e.,
shortcuts).
PMID- 25852517
TI - The social life of voices: studying the neural bases for the expression and
perception of the self and others during spoken communication.
PMID- 25852518
TI - A pilot study on the effect of cognitive training on BDNF serum levels in
individuals with Parkinson's disease.
AB - Parkinson's disease (PD) patients, besides motor dysfunctions, may also display
mild cognitive deficits (MCI) which increase with disease progression. The
neurotrophin brain-derived neurotrophic factor (BDNF) plays a role in the
survival of dopaminergic neurons and in the regulation of synaptic connectivity.
Moreover, the brain and peripheral level of this protein may be significantly
reduced in PD patients. These data suggest that a cognitive rehabilitation
protocol aimed at restoring cognitive deficits in PD patients may also involve
changes in this neurotrophin. Thus, in this pilot study we evaluated the effect
of a cognitive rehabilitation protocol focused on the training of executive
functioning and measured BDNF serum levels in a group of PD patients with mild
cognitive impairment, as compared to the effect of a placebo treatment (n = 7/8
group). The results showed that PD patients undergoing the cognitive
rehabilitation, besides improving their cognitive performance as measured with
the Zoo Map Test, also displayed increased serum BDNF levels as compared to the
placebo group. These findings suggest that BDNF serum levels may represent a
biomarker of the effects of cognitive rehabilitation in PD patients affected by
MCI. However, the functional significance of this increase in PD as well as other
neuropathological conditions remains to be determined.
PMID- 25852519
TI - Plasma oxytocin explains individual differences in neural substrates of social
perception.
AB - The neuropeptide oxytocin plays a critical role in social cognition and behavior.
A number of studies using intranasal administration have demonstrated that
oxytocin improves social perception. However, little is known about the
relationship between individual differences in endogenous levels of oxytocin and
social cognition. In the current study, we assessed the relationship between
endogenous oxytocin and brain activity during an animacy perception paradigm.
Thirty-seven male participants underwent scanning and provided a blood sample for
oxytocin analysis. In line with previous research, perception of animacy was
associated with activations in superior temporal sulcus, inferior frontal gyrus,
and medial prefrontal cortex (mPFC). Notably, participants' levels of plasma
oxytocin robustly predicted activation in areas critical for social cognitive
processes, such that higher oxytocin levels were related to increased activity in
dorsal mPFC, ventral mPFC, dorsolateral PFC, superior temporal gyrus, and
temporoparietal junction (TPJ), suggesting differential processing of social
stimuli. Together these results show that stable variations in endogenous
oxytocin levels explain individual differences in social perception.
PMID- 25852522
TI - A real-life illusion of assimilation in the human face: eye size illusion caused
by eyebrows and eye shadow.
AB - Does an assimilative illusion like the Delboeuf illusion occur in the human face?
We investigated factors that might influence the perceived size of the eyes in a
realistic face. Experiment 1 manipulated the position of the eyebrows (high or
low), the presence/absence of eye shadow, and the viewing distance (0.6 m or 5
m), then measured the perceived eye size using a psychophysical method. The
results showed that low eyebrows (i.e., closer to the eyes) make the eyes appear
larger, suggesting that the assimilation of eyes into the eyebrows is stronger
when the eye-eyebrow distance is shorter. The results also demonstrated that the
application of eye shadow also makes the eyes look larger. Moreover, the effect
of eye shadow is more pronounced when viewed from a distance. In order to
investigate the mechanism of the eye size illusion demonstrated in Experiment 1,
Experiment 2 measured the magnitude of the Delboeuf illusion at a viewing
distance of 0.6 m or 5 m, with or without gray gradation simulating the eye
shadow that was used in Experiment 1. The experiment demonstrated that the
Delboeuf illusion is modulated by viewing distance and gradation in the same way
as the eye size illusion. These results suggest that the eye size illusion
induced by the eyebrows and the Delboeuf illusion involve the same mechanism, and
that eye shadow causes the assimilation of the eyes into itself and enhances
assimilation between the eyes and the eyebrows.
PMID- 25852521
TI - Greater widespread functional connectivity of the caudate in older adults who
practice kripalu yoga and vipassana meditation than in controls.
AB - There has been a growing interest in understanding how contemplative practices
affect brain functional organization. However, most studies have restricted their
exploration to predefined networks. Furthermore, scientific comparisons of
different contemplative traditions are largely lacking. Here we explored
differences in whole brain resting state functional connectivity between
experienced yoga practitioners, experienced meditators, and matched controls.
Analyses were repeated in an independent sample of experienced meditators and
matched controls. Analyses utilizing Network-Based Statistics (Zalesky et al.,
2010) revealed difference components for yoga practitioners > controls and
meditators > controls in which the right caudate was a central node. Follow up
analyses revealed that yoga practitioners and meditators had significantly
greater degree centrality in the caudate than controls. This greater degree
centrality was not driven by single connections but by greater connectivity
between the caudate and numerous brain regions. Findings of greater caudate
connectivity in meditators than in controls was replicated in an independent
dataset. These findings suggest that yoga and meditation practitioners have
stronger functional connectivity within basal ganglia cortico-thalamic feedback
loops than non-practitioners. Although we could not provide evidence for its
mechanistic role, this greater connectivity might be related to the often
reported effects of meditation and yoga on behavioral flexibility, mental health,
and well-being.
PMID- 25852520
TI - Aberrant cerebellar connectivity in motor and association networks in
schizophrenia.
AB - Schizophrenia is a devastating illness characterized by disturbances in multiple
domains. The cerebellum is involved in both motor and non-motor functions, and
the "cognitive dysmetria" and "dysmetria of thought" models propose that
abnormalities of the cerebellum may contribute to schizophrenia signs and
symptoms. The cerebellum and cerebral cortex are reciprocally connected via a
modular, closed-loop network architecture, but few schizophrenia neuroimaging
studies have taken into account the topographical and functional heterogeneity of
the cerebellum. In this study, using a previously defined 17-network cerebral
cortical parcellation system as the basis for our functional connectivity seeds,
we systematically investigated connectivity abnormalities within the cerebellum
of 44 schizophrenia patients and 28 healthy control participants. We found
selective alterations in cerebro-cerebellar functional connectivity.
Specifically, schizophrenia patients showed decreased cerebro-cerebellar
functional connectivity in higher level association networks (ventral attention,
salience, control, and default mode networks) relative to healthy control
participants. Schizophrenia patients also showed increased cerebro-cerebellar
connectivity in somatomotor and default mode networks, with the latter showing no
overlap with the regions found to be hypoconnected within the same default mode
network. Finally, we found evidence to suggest that somatomotor and default mode
networks may be inappropriately linked in schizophrenia. The relationship of
these dysconnectivities to schizophrenia symptoms, such as neurological soft
signs and altered sense of agency, is discussed. We conclude that the cerebellum
ought to be considered for analysis in all future studies of network
abnormalities in SZ, and further suggest the cerebellum as a potential target for
further elucidation, and possibly treatment, of the underlying mechanisms and
network abnormalities producing symptoms of schizophrenia.
PMID- 25852523
TI - The Two-Wrongs model explains perception-action dissociations for illusions
driven by distortions of the egocentric reference frame.
AB - Several studies have demonstrated a dissociation of the effects of illusion on
perception and action, with perception generally reported to be susceptible to
illusions, while actions are seemingly immune. These findings have been
interpreted to support Milner and Goodale's Two Visual Systems model, which
proposes the existence of separate visual processing streams for perception and
action. However, an alternative interpretation suggests that this type of
behavioral dissociation will occur for any illusion that is caused by a
distortion of the observer's egocentric reference frame, without requiring the
existence of separate perception and action systems that are differently affected
by the illusion. In this scenario, movements aimed at illusory targets will be
accurate if they are guided within the same distorted reference frame used for
target encoding, since the error of motor guidance will cancel with the error of
encoding (hence, for actions, two wrongs do make a right). We further test this
Two-Wrongs model by examining two illusions for which the hypothesis makes very
different predictions: the rod-and-frame illusion (which affects perception but
not actions) and the simultaneous-tilt illusion (which affects perception and
actions equally). We demonstrate that the rod-and-frame illusion is caused by a
distortion of the observer's egocentric reference frame suitable for the
cancellation of errors predicted by the Two-Wrongs model. In contrast, the
simultaneous-tilt illusion is caused by local interactions between stimulus
elements within an undistorted reference frame, precluding the cancellation of
errors associated with the Two-Wrongs model such that the illusion is reflected
in both perception and actions. These results provide evidence for a class of
illusions that lead to dissociations of perception and action through distortions
of the observer's spatial reference frame, rather than through the actions of
functionally separate visual processing streams.
PMID- 25852525
TI - A commentary on: Affective coding: the emotional dimension of agency.
PMID- 25852526
TI - Cardiovascular and nervous system changes during meditation.
AB - BACKGROUND: A number of benefits have been described for the long-term practice
of meditation, yet little is known regarding the immediate neurological and
cardiovascular responses to meditation. Wireless sensor technology allows, for
the first time, multi-parameter and quantitative monitoring of an individual's
responses during meditation. The present study examined inter-individual
variations to meditation through continuous monitoring of EEG, blood pressure,
heart rate and its variability (HRV) in novice and experienced meditators.
METHODS: Participants were 20 experienced and 20 novice meditators involved in a
week-long wellness retreat. Monitoring took place during meditation sessions on
the first and last full days of the retreat. All participants wore a patch that
continuously streamed ECG data, while half of them also wore a wireless EEG
headset plus a non-invasive continuous blood pressure monitor. RESULTS:
Meditation produced variable but characteristic EEG changes, significantly
different from baseline, even among novice meditators on the first day. In
addition, although participants were predominately normotensive, the mean
arterial blood pressure fell a small (2-3 mmHg) but significant (p < 0.0001)
amount during meditation. The effect of meditation on HRV was less clear and
influenced by calculation technique and respiration. No clear relationship
between EEG changes, HRV alterations, or mean blood pressure during meditation
was found. CONCLUSION: This is the first study to investigate neurological and
cardiovascular responses during meditation in both novice and experienced
meditators using novel, wearable, wireless devices. Meditation produced varied
inter-individual physiologic responses. These results support the need for
further investigation of the short- and long-term cardiovascular effects of
mental calm and individualized ways to achieve it.
PMID- 25852524
TI - Over my fake body: body ownership illusions for studying the multisensory basis
of own-body perception.
AB - Which is my body and how do I distinguish it from the bodies of others, or from
objects in the surrounding environment? The perception of our own body and more
particularly our sense of body ownership is taken for granted. Nevertheless,
experimental findings from body ownership illusions (BOIs), show that under
specific multisensory conditions, we can experience artificial body parts or fake
bodies as our own body parts or body, respectively. The aim of the present paper
is to discuss how and why BOIs are induced. We review several experimental
findings concerning the spatial, temporal, and semantic principles of crossmodal
stimuli that have been applied to induce BOIs. On the basis of these principles,
we discuss theoretical approaches concerning the underlying mechanism of BOIs. We
propose a conceptualization based on Bayesian causal inference for addressing how
our nervous system could infer whether an object belongs to our own body, using
multisensory, sensorimotor, and semantic information, and we discuss how this can
account for several experimental findings. Finally, we point to neural network
models as an implementational framework within which the computational problem
behind BOIs could be addressed in the future.
PMID- 25852527
TI - Synchrony between sensory and cognitive networks is associated with subclinical
variation in autistic traits.
AB - Individuals with autistic spectrum disorders exhibit distinct personality traits
linked to attentional, social, and affective functions, and those traits are
expressed with varying levels of severity in the neurotypical and subclinical
population. Variation in autistic traits has been linked to reduced functional
and structural connectivity (i.e., underconnectivity, or reduced synchrony) with
neural networks modulated by attentional, social, and affective functions. Yet,
it remains unclear whether reduced synchrony between these neural networks
contributes to autistic traits. To investigate this issue, we used functional
magnetic resonance imaging to record brain activation while neurotypical
participants who varied in their subclinical scores on the Autism-Spectrum
Quotient (AQ) viewed alternating blocks of social and nonsocial stimuli (i.e.,
images of faces and of landscape scenes). We used independent component analysis
(ICA) combined with a spatiotemporal regression to quantify synchrony between
neural networks. Our results indicated that decreased synchrony between the
executive control network (ECN) and a face-scene network (FSN) predicted higher
scores on the AQ. This relationship was not explained by individual differences
in head motion, preferences for faces, or personality variables related to social
cognition. Our findings build on clinical reports by demonstrating that reduced
synchrony between distinct neural networks contributes to a range of subclinical
autistic traits.
PMID- 25852528
TI - Evidence for an inhibitory-control theory of the reasoning brain.
AB - In this article, we first describe our general inhibitory-control theory and,
then, we describe how we have tested its specific hypotheses on reasoning with
brain imaging techniques in adults and children. The innovative part of this
perspective lies in its attempt to come up with a brain-based synthesis of Jean
Piaget's theory on logical algorithms and Daniel Kahneman's theory on intuitive
heuristics.
PMID- 25852530
TI - Deep networks for motor control functions.
AB - The motor system generates time-varying commands to move our limbs and body.
Conventional descriptions of motor control and learning rely on dynamical
representations of our body's state (forward and inverse models), and control
policies that must be integrated forward to generate feedforward time-varying
commands; thus these are representations across space, but not time. Here we
examine a new approach that directly represents both time-varying commands and
the resulting state trajectories with a function; a representation across space
and time. Since the output of this function includes time, it necessarily
requires more parameters than a typical dynamical model. To avoid the problems of
local minima these extra parameters introduce, we exploit recent advances in
machine learning to build our function using a stacked autoencoder, or deep
network. With initial and target states as inputs, this deep network can be
trained to output an accurate temporal profile of the optimal command and state
trajectory for a point-to-point reach of a non-linear limb model, even when
influenced by varying force fields. In a manner that mirrors motor babble, the
network can also teach itself to learn through trial and error. Lastly, we
demonstrate how this network can learn to optimize a cost objective. This
functional approach to motor control is a sharp departure from the standard
dynamical approach, and may offer new insights into the neural implementation of
motor control.
PMID- 25852531
TI - Neural dynamics based on the recognition of neural fingerprints.
AB - Experimental evidence has revealed the existence of characteristic spiking
features in different neural signals, e.g., individual neural signatures
identifying the emitter or functional signatures characterizing specific tasks.
These neural fingerprints may play a critical role in neural information
processing, since they allow receptors to discriminate or contextualize incoming
stimuli. This could be a powerful strategy for neural systems that greatly
enhances the encoding and processing capacity of these networks. Nevertheless,
the study of information processing based on the identification of specific
neural fingerprints has attracted little attention. In this work, we study (i)
the emerging collective dynamics of a network of neurons that communicate with
each other by exchange of neural fingerprints and (ii) the influence of the
network topology on the self-organizing properties within the network. Complex
collective dynamics emerge in the network in the presence of stimuli. Predefined
inputs, i.e., specific neural fingerprints, are detected and encoded into
coexisting patterns of activity that propagate throughout the network with
different spatial organization. The patterns evoked by a stimulus can survive
after the stimulation is over, which provides memory mechanisms to the network.
The results presented in this paper suggest that neural information processing
based on neural fingerprints can be a plausible, flexible, and powerful strategy.
PMID- 25852529
TI - Dysfunctional Activation and Brain Network Profiles in Youth with Obsessive
Compulsive Disorder: A Focus on the Dorsal Anterior Cingulate during Working
Memory.
AB - Brain network dysfunction is emerging as a central biomarker of interest in
psychiatry, in large part, because psychiatric conditions are increasingly seen
as disconnection syndromes. Understanding dysfunctional brain network profiles in
task-active states provides important information on network engagement in an
experimental context. This in turn may be predictive of many of the cognitive and
behavioral deficits associated with complex behavioral phenotypes. Here we
investigated brain network profiles in youth with obsessive-compulsive disorder
(OCD), contrasting them with a group of age-comparable controls. Network
interactions were assessed during simple working memory: in particular, we
focused on the modulation by the dorsal anterior cingulate cortex (dACC) of
cortical, striatal, and thalamic regions. The focus on the dACC was motivated by
its hypothesized role in the pathophysiology of OCD. However, its task-active
network signatures have not been investigated before. Network interactions were
modeled using psychophysiological interaction, a simple directional model of seed
to target brain interactions. Our results indicate that OCD is characterized by
significantly increased dACC modulation of cortical, striatal, and thalamic
targets during working memory, and that this aberrant increase in OCD patients is
maintained regardless of working memory demand. The results constitute compelling
evidence of dysfunctional brain network interactions in OCD and suggest that
these interactions may be related to a combination of network inefficiencies and
dACC hyper-activity that has been associated with the phenotype.
PMID- 25852532
TI - On the relationship among different motor processes: a computational modeling
approach.
PMID- 25852533
TI - RM-SORN: a reward-modulated self-organizing recurrent neural network.
AB - Neural plasticity plays an important role in learning and memory. Reward
modulation of plasticity offers an explanation for the ability of the brain to
adapt its neural activity to achieve a rewarded goal. Here, we define a neural
network model that learns through the interaction of Intrinsic Plasticity (IP)
and reward-modulated Spike-Timing-Dependent Plasticity (STDP). IP enables the
network to explore possible output sequences and STDP, modulated by reward,
reinforces the creation of the rewarded output sequences. The model is tested on
tasks for prediction, recall, non-linear computation, pattern recognition, and
sequence generation. It achieves performance comparable to networks trained with
supervised learning, while using simple, biologically motivated plasticity rules,
and rewarding strategies. The results confirm the importance of investigating the
interaction of several plasticity rules in the context of reward-modulated
learning and whether reward-modulated self-organization can explain the amazing
capabilities of the brain.
PMID- 25852534
TI - Detection of epileptiform activity in EEG signals based on time-frequency and non
linear analysis.
AB - We present a new technique for detection of epileptiform activity in EEG signals.
After preprocessing of EEG signals we extract representative features in time,
frequency and time-frequency domain as well as using non-linear analysis. The
features are extracted in a few frequency sub-bands of clinical interest since
these sub-bands showed much better discriminatory characteristics compared with
the whole frequency band. Then we optimally reduce the dimension of feature space
to two using scatter matrices. A decision about the presence of epileptiform
activity in EEG signals is made by quadratic classifiers designed in the reduced
two-dimensional feature space. The accuracy of the technique was tested on three
sets of electroencephalographic (EEG) signals recorded at the University Hospital
Bonn: surface EEG signals from healthy volunteers, intracranial EEG signals from
the epilepsy patients during the seizure free interval from within the seizure
focus and intracranial EEG signals of epileptic seizures also from within the
seizure focus. An overall detection accuracy of 98.7% was achieved.
PMID- 25852535
TI - How the credit assignment problems in motor control could be solved after the
cerebellum predicts increases in error.
AB - We present a cerebellar architecture with two main characteristics. The first one
is that complex spikes respond to increases in sensory errors. The second one is
that cerebellar modules associate particular contexts where errors have increased
in the past with corrective commands that stop the increase in error. We analyze
our architecture formally and computationally for the case of reaching in a 3D
environment. In the case of motor control, we show that there are synergies of
this architecture with the Equilibrium-Point hypothesis, leading to novel ways to
solve the motor error and distal learning problems. In particular, the presence
of desired equilibrium lengths for muscles provides a way to know when the error
is increasing, and which corrections to apply. In the context of Threshold
Control Theory and Perceptual Control Theory we show how to extend our model so
it implements anticipative corrections in cascade control systems that span from
muscle contractions to cognitive operations.
PMID- 25852537
TI - The chronic challenge-new vistas on long-term multisite contacts to the central
nervous system.
PMID- 25852536
TI - A scalable neuroinformatics data flow for electrophysiological signals using
MapReduce.
AB - Data-driven neuroscience research is providing new insights in progression of
neurological disorders and supporting the development of improved treatment
approaches. However, the volume, velocity, and variety of neuroscience data
generated from sophisticated recording instruments and acquisition methods have
exacerbated the limited scalability of existing neuroinformatics tools. This
makes it difficult for neuroscience researchers to effectively leverage the
growing multi-modal neuroscience data to advance research in serious neurological
disorders, such as epilepsy. We describe the development of the Cloudwave data
flow that uses new data partitioning techniques to store and analyze
electrophysiological signal in distributed computing infrastructure. The
Cloudwave data flow uses MapReduce parallel programming algorithm to implement an
integrated signal data processing pipeline that scales with large volume of data
generated at high velocity. Using an epilepsy domain ontology together with an
epilepsy focused extensible data representation format called Cloudwave Signal
Format (CSF), the data flow addresses the challenge of data heterogeneity and is
interoperable with existing neuroinformatics data representation formats, such as
HDF5. The scalability of the Cloudwave data flow is evaluated using a 30-node
cluster installed with the open source Hadoop software stack. The results
demonstrate that the Cloudwave data flow can process increasing volume of signal
data by leveraging Hadoop Data Nodes to reduce the total data processing time.
The Cloudwave data flow is a template for developing highly scalable neuroscience
data processing pipelines using MapReduce algorithms to support a variety of user
applications.
PMID- 25852538
TI - A case of dermatomyositis with esophageal fistula in whom blind mucosal biopsy
detected occult oropharyngeal carcinoma.
AB - We present a case of anti-transcription intermediary factor 1 (anti-TIF-1)
antibody-positive dermatomyositis with concomitant esophageal fistula and
extensive truncal erythema. The characteristic cutaneous features and presence of
anti-TIF-1 antibodies were predictive for internal malignancy. However, repeated
examinations for internal malignancy showed none, and blind mucosal biopsy was
needed to diagnose oropharyngeal carcinoma. We should note the possibility of
occult nasopharyngeal carcinoma and consider performing blind mucosal biopsy in
dermatomyositis with esophageal fistula, especially with extensive truncal
erythema.
PMID- 25852539
TI - Modified muscle transposition procedure for a case of inferior rectus muscle
aplasia.
AB - PURPOSE: We report a case of inferior rectus muscle aplasia in a 65-year-old
woman. METHODS: Images were obtained using ocular motility photography and
magnetic resonance imaging (MRI), and operative findings were analyzed. RESULTS:
A 65-year-old woman presented with marked right hypertropia. The right eye also
had microcornea, iris coloboma, and completely restricted downward movement. MRI
showed absence of the inferior rectus muscle in both eyes. During surgery, it was
confirmed that the right inferior rectus muscle was absent. The patient underwent
a muscle transposition procedure without tenotomy or muscle splitting. A superior
rectus muscle tenotomy was also performed. Postoperatively, the right eye showed
hypotropia and improved downward movement. CONCLUSION: Muscle transposition
without tenotomy or tendon splitting is a surgical option for the unusual
abnormality presented in this paper.
PMID- 25852540
TI - Compartmental distribution of GABAB receptor-mediated currents along the
somatodendritic axis of hippocampal principal cells.
AB - Activity of cortical principal cells is controlled by the GABAergic system
providing inhibition in a compartmentalized manner along their somatodendritic
axis. While GABAAR-mediated inhibitory synaptic transmission has been extensively
characterized in hippocampal principal cells, little is known about the
distribution of postsynaptic effects of GABABRs. In the present study, we have
investigated the functional localization of GABABRs and their effector inwardly
rectifying potassium (Kir3) channels by combining electrophysiological recordings
in acute rat hippocampal slices, high-resolution immunoelectron microscopic
analysis and single cell simulations. Pharmacologically isolated slow inhibitory
postsynaptic currents were elicited in the three major hippocampal principal cell
types by endogenous GABA released by electrical stimulation, photolysis of caged
GABA, as well as the canonical agonist baclofen, with the highest amplitudes
observed in the CA3. Spatially restricted currents were assessed along the axis
of principal cells by uncaging GABA in the different hippocampal layers. GABABR
mediated currents were present along the entire somatodendritic axis of principal
cells, but non-uniformly distributed: largest currents and the highest
conductance densities determined in the simulations were consistently found on
the distal apical dendrites. Finally, immunocytochemical localization of GABABRs
and Kir3 channels showed that distributions overlap but their densities diverge,
particularly on the basal dendrites of pyramidal cells. GABABRs current
amplitudes and the conductance densities correlated better with Kir3 density,
suggesting a bottlenecking effect defined by the effector channel. These data
demonstrate a compartmentalized distribution of the GABABR-Kir3 signaling cascade
and suggest differential control of synaptic transmission, dendritic integration
and synaptic plasticity at afferent pathways onto hippocampal principal cells.
PMID- 25852541
TI - Impaired emotional autobiographical memory associated with right amygdalar
hippocampal atrophy in Alzheimer's disease patients.
AB - We studied the influence of emotions on autobiographical memory (AbM) in patients
with Alzheimer's disease (AD), characteristically triggering atrophy in the
hippocampus and the amygdala, two crucial structures sustaining memory and
emotional processing. Our first aim was to analyze the influence of emotion on
AbM in AD patients, on both the proportion and the specificity of emotional
memories. Additionally, we sought to determine the relationship of emotional AbM
to amygdalar-hippocampal volumes. Eighteen prodromal to mild AD patients and 18
age-matched healthy controls were included. We obtained 30 autobiographical
memories per participant using the modified Crovitz test (MCT). Analyses were
performed on global scores, rates and specificity scores of the emotional vs.
neutral categories of memories. Amygdalar-hippocampal volumes were extracted from
3D T1-weighted MRI scans and tested for correlations with behavioral data.
Overall, AD patients displayed a deficit in emotional AbMs as they elicited less
emotional memories than the controls, however, the specificity of those memories
was preserved. The deficit likely implied retrieval or storage as it was extended
in time and without reminiscence bump effect. Global scores and rates of
emotional memories, but not the specificity scores, were correlated to right
amygdalar and hippocampal volumes, indicating that atrophy in these structures
has a central role in the deficit observed. Conversely, emotional memories were
more specific than neutral memories in both groups, reflecting an enhancement
effect of emotion that could be supported by other brain regions that are spared
during the early stages of the disease.
PMID- 25852542
TI - 'Kitchen and cooking,' a serious game for mild cognitive impairment and
Alzheimer's disease: a pilot study.
AB - Recently there has been a growing interest in employing serious games (SGs) for
the assessment and rehabilitation of elderly people with mild cognitive
impairment (MCI), Alzheimer's disease (AD), and related disorders. In the present
study we examined the acceptability of 'Kitchen and cooking' - a SG developed in
the context of the EU project VERVE (http://www.verveconsortium.eu/) - in these
populations. In this game a cooking plot is employed to assess and stimulate
executive functions (such as planning abilities) and praxis. The game is
installed on a tablet, to be flexibly employed at home and in nursing homes.
Twenty one elderly participants (9 MCI and 12 AD, including 14 outpatients and 7
patients living in nursing homes, as well as 11 apathetic and 10 non-apathetic)
took part in a 1-month trail, including a clinical and neuropsychological
assessment, and 4-week training where the participants were free to play as long
as they wanted on a personal tablet. During the training, participants met once a
week with a clinician in order to fill in self-report questionnaires assessing
their overall game experience (including acceptability, motivation, and perceived
emotions). The results of the self reports and of the data concerning game
performance (e.g., time spent playing, number of errors, etc) confirm the overall
acceptability of Kitchen and cooking for both patients with MCI and patients with
AD and related disorders, and the utility to employ it for training purposes.
Interestingly, the results confirm that the game is adapted also to apathetic
patients.
PMID- 25852543
TI - The influence of aging on the number of neurons and levels of non-phosporylated
neurofilament proteins in the central auditory system of rats.
AB - In the present study, an unbiased stereological method was used to determine the
number of all neurons in Nissl stained sections of the inferior colliculus (IC),
medial geniculate body (MGB), and auditory cortex (AC) in rats (strains Long
Evans and Fischer 344) and their changes with aging. In addition, using the
optical fractionator and western blot technique, we also evaluated the number of
SMI-32-immunoreactive (-ir) neurons and levels of non-phosphorylated
neurofilament proteins in the IC, MGB, AC, and visual cortex of young and old
rats of the two strains. The SMI-32 positive neuronal population comprises about
10% of all neurons in the rat IC, MGB, and AC and represents a prevalent
population of large neurons with highly myelinated and projecting processes. In
both Long Evans and Fischer 344 rats, the total number of neurons in the IC was
roughly similar to that in the AC. With aging, we found a rather mild and
statistically non-significant decline in the total number of neurons in all three
analyzed auditory regions in both rat strains. In contrast to this, the absolute
number of SMI-32-ir neurons in both Long Evans and Fischer 344 rats significantly
decreased with aging in all the examined structures. The western blot technique
also revealed a significant age-related decline in the levels of non
phosphorylated neurofilaments in the auditory brain structures, 30-35%. Our
results demonstrate that presbycusis in rats is not likely to be primarily
associated with changes in the total number of neurons. On the other hand, the
pronounced age-related decline in the number of neurons containing non
phosphorylated neurofilaments as well as their protein levels in the central
auditory system may contribute to age-related deterioration of hearing function.
PMID- 25852544
TI - Differences in temporal order memory among young, middle-aged, and older adults
may depend on the level of interference.
AB - Age-related changes in temporal order memory have been well documented in older
adults; however, little is known about this ability during middle age. We tested
healthy young, middle-aged, and older adults on a previously published
visuospatial temporal order memory test involving high and low interference
conditions. When interference was low, young and middle-aged adults did not
differ, but both groups significantly outperformed older adults. However, when
interference was high, significant differences were found among all three age
groups. The data provide evidence that temporal order memory may begin to decline
in middle age, particularly when temporal interference is high.
PMID- 25852545
TI - Regional and sub-regional differences in hippocampal GABAergic neuronal
vulnerability in the TgCRND8 mouse model of Alzheimer's disease.
AB - Hippocampal network activity is predominantly coordinated by gamma-amino-butyric
acid (GABA)ergic neurons. We have previously hypothesized that the altered
excitability of hippocampal neurons in Alzheimer's disease (AD), which manifests
as increased in vivo susceptibility to seizures in the TgCRND8 mouse model of AD,
may be related to disruption of hippocampal GABAergic neurons. In agreement, our
previous study in TgCRND8 mice has shown that hippocampal GABAergic neurons are
more vulnerable to AD-related neuropathology than other types of neurons. To
further explore the mechanisms behind the observed decrease of GABAergic neurons
in 6 month-old TgCRND8 mice, we assessed the relative proportion of somatostatin
(SOM), neuropeptide Y (NPY) and paravalbumin (PV) sub-types of GABAergic neurons
at the regional and sub-regional level of the hippocampus. We found that NPY
expressing GABAergic neurons were the most affected, as they were decreased in
CA1-CA2 (pyramidal-, stratum oriens, stratum radiatum and molecular layers), CA3
(specifically in the stratum oriens) and dentate gyrus (specifically in the
polymorphic layer) in TgCRND8 mice as compared to non-transgenic controls. SOM
expressing GABAergic neurons were decreased in CA1-CA2 (specifically in the
stratum oriens) and in the stratum radiatum of CA3, whereas PV neurons were
significantly altered in stratum oriens sub-region of CA3. Taken together, these
data provide new evidence for the relevance of hippocampal GABAergic neuronal
network disruption as a mechanism underlying AD sequelae such as aberrant
neuronal excitability, and further point to complex hippocampal regional and sub
regional variation in susceptibility to AD-related neuronal loss.
PMID- 25852546
TI - Transforming growth factor beta1 inhibition protects from noise-induced hearing
loss.
AB - Excessive exposure to noise damages the principal cochlear structures leading to
hearing impairment. Inflammatory and immune responses are central mechanisms in
cochlear defensive response to noise but, if unregulated, they contribute to
inner ear damage and hearing loss. Transforming growth factor beta (TGF-beta) is
a key regulator of both responses and high levels of this factor have been
associated with cochlear injury in hearing loss animal models. To evaluate the
potential of targeting TGF-beta as a therapeutic strategy for preventing or
ameliorating noise-induced hearing loss (NIHL), we studied the auditory function,
cochlear morphology, gene expression and oxidative stress markers in mice exposed
to noise and treated with TGF-beta1 peptidic inhibitors P17 and P144, just before
or immediately after noise insult. Our results indicate that systemic
administration of both peptides significantly improved both the evolution of
hearing thresholds and the degenerative changes induced by noise-exposure in
lateral wall structures. Moreover, treatments ameliorated the inflammatory state
and redox balance. These therapeutic effects were dose-dependent and more
effective if the TGF-beta1 inhibitors were administered prior to inducing the
injury. In conclusion, inhibition of TGF-beta1 actions with antagonistic peptides
represents a new, promising therapeutic strategy for the prevention and repair of
noise-induced cochlear damage.
PMID- 25852547
TI - Inner ear hair cells deteriorate in mice engineered to have no or diminished
innervation.
AB - The innervation of the inner ear critically depends on the two neurotrophins Ntf3
and Bdnf. In contrast to this molecularly well-established dependency, evidence
regarding the need of innervation for long-term maintenance of inner ear hair
cells is inconclusive, due to experimental variability. Mutant mice that lack
both neurotrophins could shed light on the long-term consequences of innervation
loss on hair cells without introducing experimental variability, but do not
survive after birth. Mutant mice with conditional deletion of both neurotrophins
lose almost all innervation by postnatal day 10 and show an initially normal
development of hair cells by this stage. No innervation remains after 3 weeks and
complete loss of all innervation results in near complete loss of outer and many
inner hair cells of the organ of Corti within 4 months. Mutants that retain one
allele of either neurotrophin have only partial loss of innervation of the organ
of Corti and show a longer viability of cochlear hair cells with more profound
loss of inner hair cells. By 10 months, hair cells disappear with a base to apex
progression, proportional to the residual density of innervation and similar to
carboplatin ototoxicity. Similar to reports of hair cell loss after
aminoglycoside treatment, blobbing of stereocilia of apparently dying hair cells
protrude into the cochlear duct. Denervation of vestibular sensory epithelia for
several months also resulted in variable results, ranging from unusual hair cells
resembling the aberrations found in the organ of Corti, to near normal hair cells
in the canal cristae. Fusion and/or resorption of stereocilia and loss of hair
cells follows a pattern reminiscent of Myo6 and Cdc42 null mice. Our data support
a role of innervation for long-term maintenance but with a remarkable local
variation that needs to be taken into account when attempting regeneration of the
organ of Corti.
PMID- 25852548
TI - Longitudinal assessment of neuropsychological and temporal/spatial gait
characteristics of elderly fallers: taking it all in stride.
AB - Gait abnormalities are linked to cognitive decline and an increased fall risk
within older adults. The present study addressed gaps from cross-sectional
studies in the literature by longitudinally examining the interplay between
temporal and spatial aspects of gait, cognitive function, age, and lower
extremity strength in elderly "fallers" and "non-fallers". Gait characteristics,
neuropsychological and physical test performance were examined at two time points
spaced a year apart in cognitively intact individuals aged 60 and older (N =
416). Mixed-model repeated-measure ANCOVAs examined temporal (step time) and
spatial (stride length) gait characteristics during a simple and cognitive-load
walking task in fallers as compared to non-fallers. Fallers consistently
demonstrated significant alterations in spatial, but not temporal, aspects of
gait as compared to non-fallers during both walking tasks. Step time became
slower as stride length shortened amongst all participants during the dual task.
Shorter strides and slower step times during the dual task were both predicted by
worse executive attention/processing speed performance. In summary, divided
attention significantly impacts spatial aspects of gait in "fallers", suggesting
stride length changes may precede declines in other neuropsychological and gait
characteristics, thereby selectively increasing fall risk. Our results indicate
that multimodal intervention approaches that integrate physical and cognitive
remediation strategies may increase the effectiveness of fall risk interventions.
PMID- 25852549
TI - Differences in cognitive aging: typology based on a community structure detection
approach.
AB - The current study investigated the extent and patterns of cognitive variability
in younger and older adults. An important novelty of this study is the use of
graph-based community structure detection analysis to map performance in a mixed
population of 79 young and 76 older adults, without separating the age groups a
priori. We identified six subgroups, with distinct patterns of neuropsychological
performance. The stability of the identified subgroups was confirmed by employing
a cross-validation support vector machine based analysis. The majority of these
subgroups comprised either young or older adults, confirming the expected role of
aging in cognitive performance. In addition, we identified a subgroup of young
and older adults who performed at a similar cognitive level of overall good
cognitive performance with slightly decreased processing speed. This result
showed that older age is not necessarily associated with general lower cognitive
performance and that being young is not necessarily associated with superior
cognitive performance. Moreover, cognitively better performing elderly had a
significantly higher level of education attainment and higher crystallized
intelligence than the other elderly, which suggests that older adults with higher
cognitive reserve may be able to cope better with age-related neurobiological
change.
PMID- 25852550
TI - Lower limb progressive resistance training improves leg strength but not gait
speed or balance in Parkinson's disease: a systematic review and meta-analysis.
AB - The use of progressive resistance training (PRT) to improve gait and balance in
people with Parkinson's disease (PD) is an emerging area of interest. However,
the main effects of PRT on lower limb functions such as gait, balance, and leg
strength in people with PD remain unclear. Therefore, the aim of the meta
analysis is to evaluate the evidence surrounding the use of PRT to improve gait
and balance in people with PD. Five electronic databases, from inception to
December 2014, were searched to identify the relevant studies. Data extraction
was performed by two independent reviewers and methodological quality was
assessed using the PEDro scale. Standardized mean differences (SMD) and 95%
confidence intervals (CIs) of fixed and random effects models were used to
calculate the effect sizes between experimental and control groups and I (2)
statistics were used to determine levels of heterogeneity. In total, seven
studies were identified consisting of 172 participants (experimental n = 84;
control n = 88). The pooled results showed a moderate but significant effect of
PRT on leg strength (SMD 1.42, 95% CI 0.464-2.376); however, no significant
effects were observed for gait speed (SMD 0.418, 95% CI -0.219 to 1.055). No
significant effects were observed for balance measures included in this review.
In conclusion, our results showed no discernable effect of PRT on gait and
balance measures, although this is likely due to the lack of studies available.
It may be suggested that PRT be performed in conjunction with balance or task
specific functional training to elicit greater lower limb functional benefits in
people with PD.
PMID- 25852552
TI - Peptide ligand recognition by G protein-coupled receptors.
AB - The past few years have seen spectacular progress in the structure determination
of G protein-coupled receptors (GPCRs). We now have structural representatives
from classes A, B, C, and F. Within the rhodopsin-like class A, most structures
belong to the alpha group, whereas fewer GPCR structures are available from the
beta, gamma, and delta groups, which include peptide GPCRs such as the receptors
for neurotensin (beta group), opioids, chemokines (gamma group), and protease
activated receptors (delta group). Structural information on peptide GPCRs is
restricted to complexes with non-peptidic drug-like antagonists with the
exception of the chemokine receptor CXCR4 that has been crystallized in the
presence of a cyclic peptide antagonist. Notably, the neurotensin receptor 1 is
to date the only peptide GPCR whose structure has been solved in the presence of
a peptide agonist. Although limited in number, the current peptide GPCR
structures reveal great diversity in shape and electrostatic properties of the
ligand binding pockets, features that play key roles in the discrimination of
ligands. Here, we review these aspects of peptide GPCRs in view of possible
models for peptide agonist binding.
PMID- 25852553
TI - IL-1 interacts with ethanol effects on GABAergic transmission in the mouse
central amygdala.
AB - Neuroinflammation is hypothesized to enhance alcohol consumption and contribute
to the development of alcoholism. GABAergic transmission in the central amygdala
(CeA) plays an important role in the transition to alcohol dependence. Therefore,
we studied the effects of interleukin-1beta (IL-1beta), a proinflammatory
cytokine mediating ethanol-induced neuroinflammation, and its interaction with
ethanol on CeA GABAegic transmission in B6129SF2/J mice. We also assessed ethanol
intake in B6129SF2/J mice. Intake with unlimited (24 h) ethanol access was 9.2
12.7 g/kg (3-15% ethanol), while limited (2 h) access produced an intake of 4.1
+/- 0.5 g/kg (15% ethanol). In our electrophysiology experiments, we found that
recombinant IL-1beta (50 and 100 ng/ml) significantly decreased the amplitude of
evoked inhibitory postsynaptic potentials (eIPSPs), with no significant effects
on paired-pulse facilitation (PPF). IL-1beta (50 ng/ml) had dual effects on
spontaneous miniature inhibitory postsynaptic currents (mIPSCs): increasing mIPSC
frequencies in most CeA neurons, but decreasing both mIPSC frequencies and
amplitudes in a few cells. The IL-1beta receptor antagonist (IL-1ra; 100 ng/ml)
also had dual effects on mIPSCs and prevented the actions of IL-1beta on mIPSC
frequencies. These results suggest that IL-1beta can alter CeA GABAergic
transmission at pre- and postsynaptic sites. Ethanol (44 mM) significantly
increased eIPSP amplitudes, decreased PPFs, and increased mIPSC frequencies. IL
1beta did not alter ethanol's enhancement of the eIPSP amplitude, but, in IL
1beta-responsive neurons, the ethanol effects on mIPSC frequencies were lost.
Overall, our data suggest that the IL-1 system is involved in basal GABAergic
transmission and that IL-1beta interacts with the ethanol-induced facilitation of
CeA GABAergic transmission.
PMID- 25852551
TI - Central serotonin-2A (5-HT2A) receptor dysfunction in depression and epilepsy:
the missing link?
AB - 5-Hydroxytryptamine 2A receptors (5-HT2A-Rs) are G-protein coupled receptors. In
agreement with their location in the brain, they have been implicated not only in
various central physiological functions including memory, sleep, nociception,
eating and reward behaviors, but also in many neuropsychiatric disorders.
Interestingly, a bidirectional link between depression and epilepsy is suspected
since patients with depression and especially suicide attempters have an
increased seizure risk, while a significant percentage of epileptic patients
suffer from depression. Such epidemiological data led us to hypothesize that both
pathologies may share common anatomical and neurobiological alteration of the 5
HT2A signaling. After a brief presentation of the pharmacological properties of
the 5-HT2A-Rs, this review illustrates how these receptors may directly or
indirectly control neuronal excitability in most networks involved in depression
and epilepsy through interactions with the monoaminergic, GABAergic and
glutamatergic neurotransmissions. It also synthetizes the preclinical and
clinical evidence demonstrating the role of these receptors in antidepressant and
antiepileptic responses.
PMID- 25852555
TI - NK cell tolerance as the final endorsement of prenatal tolerance after in utero
hematopoietic cellular transplantation.
AB - The primary benefits of in utero hematopoietic cellular transplantation (IUHCT)
arise from transplanting curative cells prior to the immunologic maturation of
the fetus. However, this approach has been routinely successful only in the
treatment of congenital immunodeficiency diseases that include an inherent NK
cell deficiency despite the existence of normal maternal immunity in either
setting. These observations raise the possibility that fetal NK cells function as
an early barrier to allogeneic IUHCT. Herein, we summarize the findings of
previous studies of prenatal NK cell allospecific tolerance in mice and in
humans. Cumulatively, this new information reveals the complexity of the fetal
immune response in the setting of rejection or tolerance and illustrates the role
for fetal NK cells in the final endorsement of allospecific prenatal tolerance.
PMID- 25852554
TI - Rodent models to study the metabolic effects of shiftwork in humans.
AB - Our current 24-h society requires an increasing number of employees to work
nightshifts with millions of people worldwide working during the evening or
night. Clear associations have been found between shiftwork and the risk to
develop metabolic health problems, such as obesity. An increasing number of
studies suggest that the underlying mechanism includes disruption of the
rhythmically organized body physiology. Normally, daily 24-h rhythms in
physiological processes are controlled by the central clock in the brain in close
collaboration with peripheral clocks present throughout the body. Working
schedules of shiftworkers greatly interfere with these normal daily rhythms by
exposing the individual to contrasting inputs, i.e., at the one hand (dim)light
exposure at night, nightly activity and eating and at the other hand daytime
sleep and reduced light exposure. Several different animal models are being used
to mimic shiftwork and study the mechanism responsible for the observed
correlation between shiftwork and metabolic diseases. In this review we aim to
provide an overview of the available animal studies with a focus on the four most
relevant models that are being used to mimic human shiftwork: altered timing of
(1) food intake, (2) activity, (3) sleep, or (4) light exposure. For all studies
we scored whether and how relevant metabolic parameters, such as bodyweight,
adiposity and plasma glucose were affected by the manipulation. In the
discussion, we focus on differences between shiftwork models and animal species
(i.e., rat and mouse). In addition, we comment on the complexity of shiftwork as
an exposure and the subsequent difficulties when using animal models to
investigate this condition. In view of the added value of animal models over
human cohorts to study the effects and mechanisms of shiftwork, we conclude with
recommendations to improve future research protocols to study the causality
between shiftwork and metabolic health problems using animal models.
PMID- 25852556
TI - Genetic determinants for methotrexate response in juvenile idiopathic arthritis.
AB - Juvenile idiopathic arthritis (JIAs) is the most common chronic rheumatic disease
of childhood and is an important cause of disability. The folic acid analog
methotrexate is the first choice disease-modifying anti-rheumatic drug in this
disease, however, 35-45% of patients fail to respond. Molecular elements, such as
variants in genes of pharmacological relevance, influencing response to
methotrexate in JIA, would be important to individualize treatment strategies.
Several studies have evaluated the effects of candidate genetic variants in the
complex pathway of genes involved in methotrexate pharmacodynamics and
pharmacokinetics, however, results are still contrasting and no definitive
genetic marker of methotrexate response useful for the clinician to tailor
therapy of children with JIA has been identified. Recently, genome-wide
approaches have been applied, identifying new potential biological processes
involved in methotrexate response in JIA such as TGF-beta signaling and calcium
channels. If these genomic results are properly validated and integrated with
innovative analyses comprising deep sequencing, epigenetics, and
pharmacokinetics, they will greatly contribute to personalize therapy with
methotrexate in children with JIA.
PMID- 25852557
TI - M2 polarization enhances silica nanoparticle uptake by macrophages.
AB - While silica nanoparticles have enabled numerous industrial and medical
applications, their toxicological safety requires further evaluation. Macrophages
are the major cell population responsible for nanoparticle clearance in vivo. The
prevailing macrophage phenotype largely depends on the local immune status of the
host. Whereas M1-polarized macrophages are considered as pro-inflammatory
macrophages involved in host defense, M2 macrophages exhibit anti-inflammatory
and wound-healing properties, but also promote tumor growth. We employed
different models of M1 and M2 polarization: granulocyte-macrophage colony
stimulating factor/lipopolysaccharide (LPS)/interferon (IFN)-gamma was used to
generate primary human M1 cells and macrophage colony-stimulating factor (M
CSF)/interleukin (IL)-10 to differentiate M2 monocyte-derived macrophages (MDM).
PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-gamma
and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (O26 and 41
nm) and microparticles (O1.75 MUm) was quantified. At the concentration used (50
MUg/ml), silica nanoparticles did not influence cell viability as assessed by MTT
assay. Nanoparticle uptake was enhanced in M2-polarized primary human MDM
compared with M1 cells, as shown by flow cytometric and microscopic approaches.
In contrast, the uptake of microparticles did not differ between M1 and M2
phenotypes. M2 polarization was also associated with increased nanoparticle
uptake in the macrophage-like THP-1 cell line. In accordance, in vivo polarized
M2-like primary human tumor-associated macrophages obtained from lung tumors took
up more nanoparticles than M1-like alveolar macrophages isolated from the
surrounding lung tissue. In summary, our data indicate that the M2 polarization
of macrophages promotes nanoparticle internalization. Therefore, the phenotypical
differences between macrophage subsets should be taken into consideration in
future investigations on nanosafety, but might also open up therapeutic
perspectives allowing to specifically target M2 polarized macrophages.
PMID- 25852558
TI - Effect of ultra violet irradiation on the interplay between Th1 and Th2
lymphocytes.
AB - Although ultraviolet (UV) radiation is used to treat several types of diseases,
including rickets, psoriasis, eczema, and jaundice, the prolonged exposure to its
radiation may result in acute and chronic health effects particularly on the
skin, eyes, and the immune system. AIM: This study was carried out to show the
effect of UV on both of the lymphoproliferative response and their capacity to
produce IL-12 and IL-10 in mice. METHODS: Mice were exposed to whole body UVB and
tested for the effect of recovery times on lymphocyte proliferation and cytokine
production. In addition, direct irradiation of spleens and lymphocyte suspension
was carried out. Basal and mitogens-stimulated lymphocyte proliferation was
assessed by MTT assay while IL-10 and IL-12 were measured using ELISA. RESULTS:
There was a significant suppression in lymphocyte proliferation in comparison
with control. IL-12 level was significantly reduced while the level of IL-10 was
increased. Con A and PWM mitogens had no significant changes in IL-10 while Con A
caused a highly significant increase in IL-12 at day 6 of recovery in UVB body
irradiation. CONCLUSION: Exposure to UVB radiation could cause a state of immune
suppression and shifts Th1/Th2 cell response. This effect is closely associated
with the reduction of Th1 cytokines' expression and increase in Th2 cytokines'
levels.
PMID- 25852560
TI - A new classifier-based strategy for in-silico ion-channel cardiac drug safety
assessment.
AB - There is currently a strong interest in using high-throughput in-vitro ion
channel screening data to make predictions regarding the cardiac toxicity
potential of a new compound in both animal and human studies. A recent FDA think
tank encourages the use of biophysical mathematical models of cardiac myocytes
for this prediction task. However, it remains unclear whether this approach is
the most appropriate. Here we examine five literature data-sets that have been
used to support the use of four different biophysical models and one statistical
model for predicting cardiac toxicity in numerous species using various
endpoints. We propose a simple model that represents the balance between
repolarisation and depolarisation forces and compare the predictive power of the
model against the original results (leave-one-out cross-validation). Our model
showed equivalent performance when compared to the four biophysical models and
one statistical model. We therefore conclude that this approach should be further
investigated in the context of early cardiac safety screening when in-vitro
potency data is generated.
PMID- 25852561
TI - 7alpha, 25-dihydroxycholesterol-mediated activation of EBI2 in immune regulation
and diseases.
AB - EBI2, aka GPR183, is a G-couple receptor originally identified in 1993 as one of
main genes induced in Burkitt's lymphoma cell line BL41 by Epstein-Barr virus
(EBV) infection. After it was reported in 2009 that the receptor played a key
role in regulating B cell migration and responses, we initiated an effort in
looking for its endogenous ligand. In 2011 we and another group reported the
identification of 7alpha, 25-dihydroxyxcholesterol (7alpha, 25-OHC), an
oxysterol, as the likely physiological ligand of EBI2. A few subsequently
published studies further elucidated how 7alpha, 25-OHC bound to EBI2, and how a
gradient of 7alpha, 25-OHC could be generated in vivo and regulated migration,
activation, and functions of B cells, T cells, dendritic cells (DCs),
monocytes/macrophages, and astrocytes. The identification of 7alpha, 25-OHC as a
G protein-coupled receptor ligand revealed a previously unknown signaling system
of oxysterols, a class of molecules which exert profound biological functions.
Dysregulation of the synthesis or functions of these molecules is believed to
contribute to inflammation and autoimmune diseases, cardiovascular diseases,
neurodegenerative diseases, cancer as well as metabolic diseases such as
diabetes, obesity, and dyslipidemia. Therefore EBI2 may represent a promising
target for therapeutic interventions for human diseases.
PMID- 25852559
TI - Progress in antiandrogen design targeting hormone binding pocket to circumvent
mutation based resistance.
AB - Androgen receptor (AR) plays a critical role in the development and progression
of prostate cancer (PCa). Current clinically used antiandrogens such as
flutamide, bicalutamide, and newly approved enzalutamide mainly target the
hormone binding pocket (HBP) of AR. However, over time, drug resistance
invariably develops and switches these antiandrogens from antagonist to agonist
of the AR. Accumulated evidence indicates that AR mutation is an important cause
for the drug resistance. This review will give an overview of the mutation based
resistance of the current clinically used antiandrogens and the rational drug
design to overcome the resistance, provides a promising strategy for the
development of the new generation of antiandrogens targeting HBP.
PMID- 25852562
TI - Mapping residual organics and carbonate at grain boundaries and the amorphous
interphase in mouse incisor enamel.
AB - Dental enamel has evolved to resist the most grueling conditions of mechanical
stress, fatigue, and wear. Adding insult to injury, it is exposed to the
frequently corrosive environment of the oral cavity. While its hierarchical
structure is unrivaled in its mechanical resilience, heterogeneity in the
distribution of magnesium ions and the presence of Mg-substituted amorphous
calcium phosphate (Mg-ACP) as an intergranular phase have recently been shown to
increase the susceptibility of mouse enamel to acid attack. Herein we investigate
the distribution of two important constituents of enamel, residual organic matter
and inorganic carbonate. We find that organics, carbonate, and possibly water
show distinct distribution patterns in the mouse enamel crystallites, at simple
grain boundaries, and in the amorphous interphase at multiple grain boundaries.
This has implications for the resistance to acid corrosion, mechanical
properties, and the mechanism by which enamel crystals grow during amelogenesis.
PMID- 25852563
TI - The pathophysiology of intestinal lipoprotein production.
AB - Intestinal lipoprotein production is a multistep process, essential for the
absorption of dietary fats and fat-soluble vitamins. Chylomicron assembly begins
in the endoplasmic reticulum with the formation of primordial, phospholipids-rich
particles that are then transported to the Golgi for secretion. Several classes
of transporters play a role in the selective uptake and/or export of lipids
through the villus enterocytes. Once secreted in the lymph stream, triglyceride
rich lipoproteins (TRLs) are metabolized by Lipoprotein lipase (LPL), which
catalyzes the hydrolysis of triacylglycerols of very low density lipoproteins
(VLDLs) and chylomicrons, thereby delivering free fatty acids to various tissues.
Genetic mutations in the genes codifying for these proteins are responsible of
different inherited disorders affecting chylomicron metabolism. This review
focuses on the molecular pathways that modulate the uptake and the transport of
lipoproteins of intestinal origin and it will highlight recent findings on TRLs
assembly.
PMID- 25852564
TI - Physiology of pericardial fluid production and drainage.
AB - The pericardium is one of the serosal cavities of the mammals. It consists of two
anatomical structures closely connected, an external sac of fibrous connective
tissue, that is called fibrous pericardium and an internal that is called serous
pericardium coating the internal surface of the fibrous pericardium (parietal
layer) and the heart (visceral layer) forming the pericardial space. Between
these two layers a small amount of fluid exists that is called pericardial fluid.
The pericardial fluid is a product of ultrafiltration and is considered to be
drained by lymphatic capillary bed mainly. Under normal conditions it provides
lubrication during heart beating while the mesothelial cells that line the
membrane may also have a role in the absorption of the pericardial fluid along
with the pericardial lymphatics. Here, we provide a review of the the current
literature regarding the physiology of the pericardial space and the regulation
of pericardial fluid turnover and highlight the areas that need to be further
investigated.
PMID- 25852565
TI - Leucine minimizes denervation-induced skeletal muscle atrophy of rats through
akt/mtor signaling pathways.
AB - The aim of the present study was to evaluate the effect of leucine treatment
(0.30 mM) on muscle weight and signaling of myoproteins related to synthesis and
degradation pathways of soleus muscle following seven days of complete sciatic
nerve lesion. Wistar rats (n = 24) of 3-4 months of age (192 +/- 23 g) were used.
The animals were randomly distributed into four experimental groups (n =
6/group): control, treated with leucine (L), denervated (D) and denervated
treated with leucine (DL). Dependent measures were proteins levels of AKT, AMPK,
mTOR, and ACC performed by Western blot. Leucine induced a reduction in the
phosphorylation of AMPK (p < 0.05) by 16% in the L and by 68% in the DL groups as
compared with control group. Denervation increased AMPK by 24% in the D group as
compared with the control group (p < 0.05). AKT was also modulated by denervation
and leucine treatment, highlighted by the elevation of AKT phosphorylation in the
D (65%), L (98%) and DL (146%) groups as compared with the control group (p <
0.05). AKT phosphorylation was 49% higher in the D group as compared with the DL
group. Furthermore, denervation decreased mTOR phosphorylation by 29% in the D
group as compared with the control group. However, leucine treatment induced an
increase of 49% in the phosphorylation of mTOR in the L group as compared with
the control group, and an increase of 154% in the DL as compared with the D group
(p < 0.05). ACC phosphorylation was 20% greater in the D group than the control
group. Furthermore, ACC in the soleus was 22% lower in the in the L group and 50%
lower in the DL group than the respective control group (p < 0.05). In
conclusion, leucine treatment minimized the deleterious effects of denervation on
rat soleus muscle by increasing anabolic (AKT and mTOR) and decreasing catabolic
(AMPK) pathways. These results may be interesting for muscle recovery following
acute denervation, which may contribute to musculoskeletal rehabilitation after
denervation.
PMID- 25852566
TI - Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca(2+)
homeostasis.
AB - A series of recent studies report novel roles for Pak1, a key member of the
highly conserved family of serine-threonine protein kinases regulated by Ras
related small G-proteins, Cdc42/Rac1, in cardiac physiology and cardioprotection.
Previous studies had identified Pak1 in the regulation of hypertrophic remodeling
that could potentially lead to heart failure. This article provides a review of
more recent findings on the roles of Pak1 in cardiac Ca(2+) homeostasis. These
findings identified crucial roles for Pak1 in cardiomyocyte Ca(2+) handling and
demonstrated that it functions through unique mechanisms involving regulation of
the post-transcriptional activity of key Ca(2+)-handling proteins, including the
expression of Ca(2+)-ATPase SERCA2a, along with the speculative possibility of an
involvement in the maintenance of transverse (T)-tubular structure. They
highlight important regulatory functions of Pak1 in Ca(2+) homeostasis in cardiac
cells, and identify novel potential therapeutic strategies directed at
manipulation of Pak1 signaling for the management of cardiac disease,
particularly heart failure.
PMID- 25852567
TI - Abnormal calcium homeostasis in heart failure with preserved ejection fraction is
related to both reduced contractile function and incomplete relaxation: an
electromechanically detailed biophysical modeling study.
AB - Heart failure with preserved ejection fraction (HFpEF) accounts for about 50% of
heart failure cases. It has features of incomplete relaxation and increased
stiffness of the left ventricle. Studies from clinical electrophysiology and
animal experiments have found that HFpEF is associated with impaired calcium
homeostasis, ion channel remodeling and concentric left ventricle hypertrophy
(LVH). However, it is still unclear how the abnormal calcium homeostasis, ion
channel and structural remodeling affect the electro-mechanical dynamics of the
ventricles. In this study we have developed multiscale models of the human left
ventricle from single cells to the 3D organ, which take into consideration HFpEF
induced changes in calcium handling, ion channel remodeling and concentric LVH.
Our simulation results suggest that at the cellular level, HFpEF reduces the
systolic calcium level resulting in a reduced systolic contractile force, but
elevates the diastolic calcium level resulting in an abnormal residual diastolic
force. In our simulations, these abnormal electro-mechanical features of the
ventricular cells became more pronounced with the increase of the heart rate.
However, at the 3D organ level, the ejection fraction of the left ventricle was
maintained due to the concentric LVH. The simulation results of this study mirror
clinically observed features of HFpEF and provide new insights toward the
understanding of the cellular bases of impaired cardiac electromechanical
functions in heart failure.
PMID- 25852570
TI - The calcium-ROS-pH triangle and mitochondrial permeability transition: challenges
to mimic cardiac ischemia-reperfusion.
PMID- 25852571
TI - Commentary on: "Tissue engineering: How to build a heart".
PMID- 25852569
TI - TGF-beta/Smad signaling in renal fibrosis.
AB - TGF-beta (transforming growth factor-beta) is well identified as a central
mediator in renal fibrosis. TGF-beta initiates canonical and non-canonical
pathways to exert multiple biological effects. Among them, Smad signaling is
recognized as a major pathway of TGF-beta signaling in progressive renal
fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated
with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases
dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7
leads to accumulation and activation of myofibroblasts, overproduction of ECM
(extracellular matrix), and reduction in ECM degradation in the diseased kidney.
Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for
renal fibrosis in various models of kidney diseases. In contrast, another
downstream effecter of TGF-beta/Smad signaling pathway, Smad2, exerts its renal
protective role by counter-regulating the Smad3. Furthermore, recent studies
demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR
200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR
200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3
mediated renal fibrosis in various mouse models of chronic kidney diseases (CKD).
Taken together, TGF-beta/Smad signaling plays an important role in renal
fibrosis. Targeting TGF-beta/Smad3 signaling may represent a specific and
effective therapy for CKD associated with renal fibrosis.
PMID- 25852568
TI - Is it time to turn our attention toward central mechanisms for post-exertional
recovery strategies and performance?
AB - Key PointsCentral fatigue is accepted as a contributor to overall athletic
performance, yet little research directly investigates post-exercise recovery
strategies targeting the brainCurrent post-exercise recovery strategies likely
impact on the brain through a range of mechanisms, but improvements to these
strategies is neededResearch is required to optimize post-exercise recovery with
a focus on the brain Post-exercise recovery has largely focused on peripheral
mechanisms of fatigue, but there is growing acceptance that fatigue is also
contributed to through central mechanisms which demands that attention should be
paid to optimizing recovery of the brain. In this narrative review we assemble
evidence for the role that many currently utilized recovery strategies may have
on the brain, as well as potential mechanisms for their action. The review
provides discussion of how common nutritional strategies as well as physical
modalities and methods to reduce mental fatigue are likely to interact with the
brain, and offer an opportunity for subsequent improved performance. We aim to
highlight the fact that many recovery strategies have been designed with the
periphery in mind, and that refinement of current methods are likely to provide
improvements in minimizing brain fatigue. Whilst we offer a number of
recommendations, it is evident that there are many opportunities for improving
the research, and practical guidelines in this area.
PMID- 25852572
TI - AMP-activated protein kinase controls exercise training- and AICAR-induced
increases in SIRT3 and MnSOD.
AB - The mitochondrial protein deacetylase sirtuin (SIRT) 3 may mediate exercise
training-induced increases in mitochondrial biogenesis and improvements in
reactive oxygen species (ROS) handling. We determined the requirement of AMP
activated protein kinase (AMPK) for exercise training-induced increases in
skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise
training for 6.5 weeks increased SIRT3 (p < 0.01) and superoxide dismutase 2
(MnSOD; p < 0.05) protein abundance in quadriceps muscle of wild-type (WT; n = 13
15), but not AMPK alpha2 kinase dead (KD; n = 12-13) mice. We also observed a
strong trend for increased MnSOD abundance in exercise-trained skeletal muscle of
healthy humans (p = 0.051; n = 6). To further elucidate a role for AMPK in
mediating these effects, we treated WT (n = 7-8) and AMPK alpha2 KD (n = 7-9)
mice with 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). Four
weeks of daily AICAR injections (500 mg/kg) resulted in AMPK-dependent increases
in SIRT3 (p < 0.05) and MnSOD (p < 0.01) in WT, but not AMPK alpha2 KD mice. We
also tested the effect of repeated AICAR treatment on mitochondrial protein
levels in mice lacking the transcriptional coactivator peroxisome proliferator
activated receptor gamma-coactivator 1alpha (PGC-1alpha KO; n = 9-10). Skeletal
muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1alpha KO
mice (p < 0.01) and AICAR-induced increases in SIRT3 and MnSOD protein abundance
was only observed in WT mice (p < 0.05). Finally, the acetylation status of SIRT3
target lysine residues on MnSOD (K122) or oligomycin-sensitivity conferring
protein (OSCP; K139) was not altered in either mouse or human skeletal muscle in
response to acute exercise. We propose an important role for AMPK in regulating
mitochondrial function and ROS handling in skeletal muscle in response to
exercise training.
PMID- 25852573
TI - Chemical coding and chemosensory properties of cholinergic brush cells in the
mouse gastrointestinal and biliary tract.
AB - The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline
acetyltransferase (ChAT)-positive brush cells with taste cell-like traits. With
the aid of two transgenic mouse lines that express green fluorescent protein
(EGFP) under the control of the ChAT promoter (EGFP (ChAT) ) and by using in situ
hybridization and immunohistochemistry we found that EGFP (ChAT) cells were
clustered in the epithelium lining the gastric groove. EGFP (ChAT) cells were
numerous in the gall bladder and bile duct, and found scattered as solitary cells
along the small and large intestine. While all EGFP (ChAT) cells were also ChAT
positive, expression of the high-affinity choline transporter (ChT1) was never
detected. Except for the proximal colon, EGFP (ChAT) cells also lacked detectable
expression of the vesicular acetylcholine transporter (VAChT). EGFP (ChAT) cells
were found to be separate from enteroendocrine cells, however they were all
immunoreactive for cytokeratin 18 (CK18), transient receptor potential melastatin
like subtype 5 channel (TRPM5), and for cyclooxygenases 1 (COX1) and 2 (COX2).
The ex vivo stimulation of colonic EGFP (ChAT) cells with the bitter substance
denatonium resulted in a strong increase in intracellular calcium, while in other
epithelial cells such an increase was significantly weaker and also timely
delayed. Subsequent stimulation with cycloheximide was ineffective in both cell
populations. Given their chemical coding and chemosensory properties, EGFP (ChAT)
brush cells thus may have integrative functions and participate in induction of
protective reflexes and inflammatory events by utilizing ACh and prostaglandins
for paracrine signaling.
PMID- 25852574
TI - Demystifying cognitive science: explaining cognition through network-based
modeling.
PMID- 25852577
TI - Socio-Economic Status Determines Risk of Receptive Syringe Sharing Behaviors
among Iranian Drug Injectors; A National Study.
AB - BACKGROUND: Although needle and syringe sharing is one of the main routs of
transmission of HIV in several countries in the middle east, very little is known
about how socio-economic status of injecting drug users (IDUs) is linked to the
receptive syringe sharing behaviors in these countries. AIM: To study socio
economic correlates of receptive needle and syringe sharing among IDUs in Iran.
METHODS: The study used data from the Unhide Risk Study, a national survey of
IDUs. This study sampled 636 IDUs (91% male) via snowball sampling from eight
provinces in Iran in 2009. Socio-demographic and drug use characteristics were
collected. We used a logistic regression to determine factors associated with
receptive needle and syringe sharing during the past 6 months. RESULTS: From 636
IDUs enrolled in this study, 68% (n = 434) reported receptive needle and syringe
sharing behaviors in the past 6 months. Odds of receptive needle and syringe
sharing in the past 6 months was lower among IDUs who were male [odds ratios (OR)
= 0.29, 95% confidence interval (CI) = 0.12-0.70], had higher education (OR =
0.74, 95% CI = 0.64-0.86) but higher among those who were unemployed (OR = 4.05,
95% CI = 1.50-10.94), and were single (OR = 1.47, 95% CI = 1.02-2.11).
CONCLUSION: This study presented factors associated with risk of receptive needle
and syringe sharing among Iranian IDUs. This information may be used for HIV
prevention and harm reduction purposes. Socio-economic status of Iranian IDUs may
be closely linked to high-risk injecting behaviors among them.
PMID- 25852575
TI - Organization and dynamics of SNARE proteins in the presynaptic membrane.
AB - Our view of the lateral organization of lipids and proteins in the plasma
membrane has evolved substantially in the last few decades. It is widely accepted
that many, if not all, plasma membrane proteins and lipids are organized in
specific domains. These domains vary widely in size, composition, and stability,
and they represent platforms governing diverse cell functions. The presynaptic
plasma membrane is a well-studied example of a membrane which undergoes
rearrangements, especially during exo- and endocytosis. Many proteins and lipids
involved in presynaptic function are known, and major efforts have been made to
understand their spatial organization and dynamics. Here, we focus on the
mechanisms underlying the organization of SNAREs, the key proteins of the fusion
machinery, in distinct domains, and we discuss the functional significance of
these clusters.
PMID- 25852576
TI - Tetraspanins as therapeutic targets in hematological malignancy: a concise
review.
AB - Tetraspanins belong to a family of transmembrane proteins which play a major role
in the organization of the plasma membrane. While all immune cells express
tetraspanins, most of these are present in a variety of other cell types. There
are a select few, such as CD37 and CD53, which are restricted to hematopoietic
lineages. Tetraspanins associate with numerous partners involved in a diverse set
of biological processes, including cell activation, survival, proliferation,
adhesion, and migration. The historical view has assigned them a scaffolding
role, but recent discoveries suggest some tetraspanins can directly participate
in signaling through interactions with cytoplasmic proteins. Given their
potential roles in supporting tumor survival and immune evasion, an improved
understanding of tetraspanin activity could prove clinically valuable. This
review will focus on emerging data in the study of tetraspanins, advances in the
clinical development of anti-CD37 therapeutics, and the future prospects of
targeting tetraspanins in hematological malignancy.
PMID- 25852578
TI - "Diagnosis by behavioral observation" home-videosomnography - a rigorous
ethnographic approach to sleep of children with neurodevelopmental conditions.
AB - INTRODUCTION: Advanced video technology is available for sleep-laboratories.
However, low-cost equipment for screening in the home setting has not been
identified and tested, nor has a methodology for analysis of video recordings
been suggested. METHODS: We investigated different combinations of
hardware/software for home-videosomnography (HVS) and established a process for
qualitative and quantitative analysis of HVS-recordings. A case vignette (HVS
analysis for a 5.5-year-old girl with major insomnia and several co-morbidities)
demonstrates how methodological considerations were addressed and how HVS added
value to clinical assessment. RESULTS: We suggest an "ideal set of
hardware/software" that is reliable, affordable (~$500) and portable (=2.8 kg) to
conduct non-invasive HVS, which allows time-lapse analyses. The equipment
consists of a net-book, a camera with infrared optics, and a video capture
device. (1) We present an HVS-analysis protocol consisting of three steps of
analysis at varying replay speeds: (a) basic overview and classification at 16*
normal speed; (b) second viewing and detailed descriptions at 4-8* normal speed,
and (c) viewing, listening, and in-depth descriptions at real-time speed. (2) We
also present a custom software program that facilitates video analysis and note
taking (Annotator((c))), and Optical Flow software that automatically quantifies
movement for internal quality control of the HVS-recording. The case vignette
demonstrates how the HVS-recordings revealed the dimension of insomnia caused by
restless legs syndrome, and illustrated the cascade of symptoms, challenging
behaviors, and resulting medications. CONCLUSION: The strategy of using HVS,
although requiring validation and reliability testing, opens the floor for a new
"observational sleep medicine," which has been useful in describing discomfort
related behavioral movement patterns in patients with communication difficulties
presenting with challenging/disruptive sleep/wake behaviors.
PMID- 25852580
TI - Using historical accounts of harpsichord touch to empirically investigate the
production and perception of dynamics on the 1788 Taskin.
AB - This article investigates the extent of production and perception of dynamic
differences on a French historical harpsichord, extensively revised in 1788 by
Pascal Taskin. A historical review reports on the descriptions of two different
types of touch found in treatises of the 18th century. These two touches
(loud/struck and soft/pressed) were used to perform single tones on the lower,
upper, peau de buffle (PDB) registers (the last of which Taskin is credited with
having invented) and the coupled 8-foot registers to investigate differences in
dynamics. Acoustic measurements show varied differences of up to 11 dB for the
two types of touch over different pitches in each register. The strongest
difference is measured in the first harmonic of note F2 on the PDB. A listening
experiment was conducted to test whether these differences are perceivable.
Participants performed a discrimination task using pairs of single tones.
Participants were able to perform significantly better than chance in correctly
identifying whether pairs of single tones were same or different with respect to
loudness [t(24) = 12.01, p < 0.001]. Accuracies were influenced by pitch and
register, the PDB providing the strongest accuracies over the four registers
tested.
PMID- 25852579
TI - Could vagus nerve stimulation target hippocampal hyperactivity to improve
cognition in schizophrenia?
PMID- 25852581
TI - Impact of dialect use on a basic component of learning to read.
AB - Can some black-white differences in reading achievement be traced to differences
in language background? Many African American children speak a dialect that
differs from the mainstream dialect emphasized in school. We examined how use of
alternative dialects affects decoding, an important component of early reading
and marker of reading development. Behavioral data show that use of the
alternative pronunciations of words in different dialects affects reading aloud
in developing readers, with larger effects for children who use more African
American English (AAE). Mechanisms underlying this effect were explored with a
computational model, investigating factors affecting reading acquisition. The
results indicate that the achievement gap may be due in part to differences in
task complexity: children whose home and school dialects differ are at greater
risk for reading difficulties because tasks such as learning to decode are more
complex for them.
PMID- 25852582
TI - Perceiving fingers in single-digit arithmetic problems.
AB - In this study, we investigate in children the neural underpinnings of finger
representation and finger movement involved in single-digit arithmetic problems.
Evidence suggests that finger representation and finger-based strategies play an
important role in learning and understanding arithmetic. Because different
operations rely on different networks, we compared activation for subtraction and
multiplication problems in independently localized finger somatosensory and motor
areas and tested whether activation was related to skill. Brain activations from
children between 8 and 13 years of age revealed that only subtraction problems
significantly activated finger motor areas, suggesting reliance on finger-based
strategies. In addition, larger subtraction problems yielded greater
somatosensory activation than smaller problems, suggesting a greater reliance on
finger representation for larger numerical values. Interestingly, better
performance in subtraction problems was associated with lower activation in the
finger somatosensory area. Our results support the importance of fine-grained
finger representation in arithmetical skill and are the first neurological
evidence for a functional role of the somatosensory finger area in proficient
arithmetical problem solving, in particular for those problems requiring quantity
manipulation. From an educational perspective, these results encourage
investigating whether different finger-based strategies facilitate arithmetical
understanding and encourage educational practices aiming at integrating finger
representation and finger-based strategies as a tool for instilling stronger
numerical sense.
PMID- 25852583
TI - Up or down? Reading direction influences vertical counting direction in the
horizontal plane - a cross-cultural comparison.
AB - Most adults and children in cultures where reading text progresses from left to
right also count objects from the left to the right side of space. The reverse is
found in cultures with a right-to-left reading direction. The current set of
experiments investigated whether vertical counting in the horizontal plane is
also influenced by reading direction. Participants were either from a left-to
right reading culture (UK) or from a mixed (left-to-right and top-to-bottom)
reading culture (Hong Kong). In Experiment 1, native English-speaking children
and adults and native Cantonese-speaking children and adults performed three
object counting tasks. Objects were presented flat on a table in a horizontal,
vertical, and square display. Independent of culture, the horizontal array was
mostly counted from left to right. While the majority of English-speaking
children counted the vertical display from bottom to top, the majority of the
Cantonese-speaking children as well as both Cantonese- and English-speaking
adults counted the vertical display from top to bottom. This pattern was
replicated in the counting pattern for squares: all groups except the English
speaking children started counting with the top left coin. In Experiment 2,
Cantonese-speaking adults counted a square array of objects after they read a
text presented to them either in left-to-right or in top-to-bottom reading
direction. Most Cantonese-speaking adults started counting the array by moving
horizontally from left to right. However, significantly more Cantonese-speaking
adults started counting with a top-to-bottom movement after reading the text
presented in a top-to-bottom reading direction than in a left-to-right reading
direction. Our results show clearly that vertical counting in the horizontal
plane is influenced by longstanding as well as more recent experience of reading
direction.
PMID- 25852584
TI - Arbitrary numbers counter fair decisions: trails of markedness in card
distribution.
AB - Converging evidence from controlled experiments suggests that the mere processing
of a number and its attributes such as value or parity might affect free choice
decisions between different actions. For example the spatial numerical
associations of response codes (SNARC) effect indicates the magnitude of a digit
to be associated with a spatial representation and might therefore affect spatial
response choices (i.e., decisions between a "left" and a "right" option). At the
same time, other (linguistic) features of a number such as parity are embedded
into space and might likewise prime left or right responses through feature words
[odd or even, respectively; markedness association of response codes (MARC)
effect]. In this experiment we aimed at documenting such influences in a natural
setting. We therefore assessed number-space and parity-space association effects
by exposing participants to a fair distribution task in a card playing scenario.
Participants drew cards, read out loud their number values, and announced their
response choice, i.e., dealing it to a left vs. right player, indicated by
Playmobil characters. Not only did participants prefer to deal more cards to the
right player, the card's digits also affected response choices and led to a
slightly but systematically unfair distribution, supported by a regular SNARC
effect and counteracted by a reversed MARC effect. The experiment demonstrates
the impact of SNARC- and MARC-like biases in free choice behavior through verbal
and visual numerical information processing even in a setting with high external
validity.
PMID- 25852585
TI - Regulatory focus and generalized trust: the impact of prevention-focused self
regulation on trusting others.
AB - The current research suggests that taking self-regulatory mechanisms into account
provides insights regarding individuals' responses to threats in social
interactions. In general, based on the notion that a prevention-focused
orientation of self-regulation is associated with a need for security and a
vigilant tendency to avoid losses and other types of negative events we advocate
that a prevention-focused orientation, both as a disposition as well as a
situationally induced state, lowers generalized trust, thus hindering cooperation
within social interactions that entail threats. Specifically, we found that the
more individuals' habitual self-regulatory orientation is dominated by a
prevention focus, the less likely they are to score high on a self-report measure
of generalized trust (Study 1), and to express trust in a trust game paradigm as
manifested in lower sums of transferred money (Studies 2 and 3). Similar findings
were found when prevention focus was situationally manipulated (Study 4).
Finally, one possible factor underlying the impact of prevention-focused self
regulation on generalized trust was demonstrated as individuals with a special
sensitivity to negative information were significantly affected by a subtle
prevention focus manipulation (versus control condition) in that they reacted
with reduced trust in the trust game (Study 5). In sum, the current findings
document the crucial relevance of self-regulatory orientations as conceptualized
in regulatory focus theory regarding generalized trust and responses to threats
within a social interaction. The theoretical and applied implications of the
findings are discussed.
PMID- 25852586
TI - Catecholamine responses to virtual combat: implications for post-traumatic stress
and dimensions of functioning.
AB - Posttraumatic stress disorder (PTSD) symptoms can result in functional impairment
among service members (SMs), even in those without a clinical diagnosis. The
variability in outcomes may be related to underlying catecholamine mechanisms.
Individuals with PTSD tend to have elevated basal catecholamine levels, though
less is known regarding catecholamine responses to trauma-related stimuli. We
assessed whether catecholamine responses to a virtual combat environment impact
the relationship between PTSD symptom clusters and elements of functioning.
Eighty-seven clinically healthy SMs, within 2 months after deployment to Iraq or
Afghanistan, completed self-report measures, viewed virtual-reality (VR) combat
sequences, and had sequential blood draws. Norepinephrine responses to VR combat
exposure moderated the relationship between avoidance symptoms and scales of
functioning including physical functioning, physical-role functioning, and
vitality. Among those with high levels of avoidance, norepinephrine change was
inversely associated with functional status, whereas a positive correlation was
observed for those with low levels of avoidance. Our findings represent a novel
use of a virtual environment to display combat-related stimuli to returning SMs
to elucidate mind-body connections inherent in their responses. The insight
gained improves our understanding of post-deployment symptoms and quality of life
in SMs and may facilitate enhancements in treatment. Further research is needed
to validate these findings in other populations and to define the implications
for treatment effectiveness.
PMID- 25852587
TI - Disagreeing in context.
AB - This paper argues for contextualism about predicates of personal taste and
evaluative predicates in general, and offers a proposal of how apparently
resilient disagreements are to be explained. The present proposal is
complementary to others that have been made in the recent literature. Several
authors, for instance (Lopez de Sa, 2008; Sundell, 2011; Huvenes, 2012; Marques
and Garcia-Carpintero, 2014; Marques, 2014a), have recently defended semantic
contextualism for those kinds of predicates from the accusation that it faces the
problem of lost disagreement. These authors have proposed that a proper account
of the resilient disagreement in the cases studied is to be achieved by an appeal
to pragmatic processes, and to conflicting non-doxastic attitudes. It is argued
here that the existing contextualist solutions are incomplete as they stand, and
are subject to objections because of this. A supplementation of contextualism is
offered, together with an explanation of why failed presuppositions of
commonality (Lopez de Sa), disputes over the appropriateness of a contextually
salient standard (Sundell), and differences in non-doxastic attitudes (Sundell,
Huvenes, Marques, and Garcia-Carpintero) give rise to conflicts. This paper
claims that conflicts of attitudes are the reason why people still have
impressions of disagreement in spite of failed commonality presuppositions, that
those conflicts drive metalinguistic disputes over the selection of appropriate
standards, and hence conflicting non-doxastic attitudes demand an explanation
that is independent of those context dependent pragmatic processes. The paper
further argues that the missing explanation is 2-fold: first, disagreement
prevails where the properties expressed by taste and value predicates are
response-dependent properties, and, secondly, it prevails where those response
dependent properties are involved in evolved systems of coordination that respond
to evolutionarily recurrent situations.
PMID- 25852588
TI - The relationship between deferred imitation, associative memory, and
communication in 14-months-old children. Behavioral and electrophysiological
indices.
AB - The present study combines behavioral observations of memory (deferred imitation,
DI, after a brief delay of 30 min and after a long delay of 2-3 weeks) and
electrophysiological (event-related potentials, ERPs) measures of associative
memory, as well as parental reports of non-verbal and verbal communication in
sixteen 14-months-old children. Results show that for DI, the children remembered
the stimulus after the brief but not after the long delay. There was a clear
electrophysiological response indicating associative memory. Furthermore, a
correlation between DI and ERP suggests that both measures of memory (DI and
associative memory) tap into similar mechanisms in 14-months-old children. There
was also a statistically significant relation between parental report of
receptive (verbal) language and the ERP, showing an association between receptive
language skills and associative memory.
PMID- 25852589
TI - The complex duration perception of emotional faces: effects of face direction.
AB - The perceived duration of emotional face stimuli strongly depends on the
expressed emotion. But, emotional faces also differ regarding a number of other
features like gaze, face direction, or sex. Usually, these features have been
controlled by only using pictures of female models with straight gaze and face
direction. Doi and Shinohara (2009) reported that an overestimation of angry
faces could only be found when the model's gaze was oriented toward the observer.
We aimed at replicating this effect for face direction. Moreover, we explored the
effect of face direction on the duration perception sad faces. Controlling for
the sex of the face model and the participant, female and male participants rated
the duration of neutral, angry, and sad face stimuli of both sexes photographed
from different perspectives in a bisection task. In line with current findings,
we report a significant overestimation of angry compared to neutral face stimuli
that was modulated by face direction. Moreover, the perceived duration of sad
face stimuli did not differ from that of neutral faces and was not influenced by
face direction. Furthermore, we found that faces of the opposite sex appeared to
last longer than those of the same sex. This outcome is discussed with regards to
stimulus parameters like the induced arousal, social relevance, and an
evolutionary context.
PMID- 25852590
TI - Empathy and nonattachment independently predict peer nominations of prosocial
behavior of adolescents.
AB - There is a plethora of research showing that empathy promotes prosocial behavior
among young people. We examined a relatively new construct in the mindfulness
literature, nonattachment, defined as a flexible way of relating to one's
experiences without clinging to or suppressing them. We tested whether
nonattachment could predict prosociality above and beyond empathy. Nonattachment
implies high cognitive flexibility and sufficient mental resources to step out of
excessive self-cherishing to be there for others in need. Multilevel Poisson
models using a sample of 15-year olds (N = 1831) showed that empathy and
nonattachment independently predicted prosocial behaviors of helpfulness and
kindness, as judged by same-sex and opposite-sex peers, except for when boys
nominated girls. The effects of nonattachment remained substantial in more
conservative models including self-esteem and peer nominations of liking.
PMID- 25852591
TI - Number word structure in first and second language influences arithmetic skills.
AB - Languages differ in how they represent numerical information, and specifically
whether the verbal notation of numbers follows the same order as the symbolic
notation (in non-inverted languages, e.g., Hebrew, "25, twenty-five") or whether
the two notations diverge (in inverted languages, e.g., Arabic, "25, five-and
twenty"). We examined how the structure of number-words affects how arithmetic
operations are processed by bilingual speakers of an inverted and a non-inverted
language. We examined Arabic-Hebrew bilinguals' performance in the first
language, L1 (inverted) and in the second language, L2 (non-inverted). Their
performance was compared to that of Hebrew L1 speakers, who do not speak an
inverted language. Participants judged the accuracy of addition problems
presented aurally in L1, aurally in L2 or in visual symbolic notation. Problems
were presented such that they matched or did not match the structure of number
words in the language. Arabic-Hebrew bilinguals demonstrated both flexibility in
processing and adaptation to the language of aural-verbal presentation - they
were more accurate for the inverted order of presentation in Arabic, but more
accurate for non-inverted order of presentation in Hebrew, thus exhibiting the
same pattern found for native Hebrew speakers. In addition, whereas native Hebrew
speakers preferred the non-inverted order in visual symbolic presentation as
well, the Arabic-Hebrew bilinguals showed enhanced flexibility, without a
significant preference for one order over the other, in either speed or accuracy.
These findings suggest that arithmetic processing is sensitive to the linguistic
representations of number words. Moreover, bilinguals exposed to inverted and non
inverted languages showed influence of both systems, and enhanced flexibility in
processing. Thus, the L1 does not seem to have exclusive power in shaping
numerical mental representations, but rather the system remains open to
influences from a later learned L2.
PMID- 25852592
TI - New drugs and polydrug use: implications for clinical psychology.
PMID- 25852593
TI - Turn-timing in signed conversations: coordinating stroke-to-stroke turn
boundaries.
AB - In spoken interactions, interlocutors carefully plan, and time their utterances,
minimizing gaps and overlaps between consecutive turns. Cross-linguistic
comparison has indicated that spoken languages vary only minimally in terms of
turn-timing, and language acquisition research has shown pre-linguistic vocal
turn-taking in the first half year of life. These observations suggest that the
turn-taking system may provide a fundamental basis for our linguistic capacities.
The question remains, however, to what extent our capacity for rapid turn-taking
is determined by modality constraints. The avoidance of overlapping turns could
be motivated by the difficulty of hearing and speaking at the same time. If so,
turn-taking in sign might show greater toleration for overlap. Alternatively,
signed conversations may show a similar distribution of turn-timing as spoken
languages, thus avoiding both gaps and overlaps. To address this question we look
at turn-timing in question-answer sequences in spontaneous conversations of Sign
Language of the Netherlands. The findings indicate that although there is
considerable overlap in two or more signers' articulators in conversation, when
proper allowance is made for onset preparation, post-utterance retraction and the
intentional holding of signs for response, turn-taking latencies in sign look
remarkably like those reported for spoken language. This is consistent with the
possibility that, at least with regard to responses to questions, speakers and
signers follow similar time courses in planning and producing their utterances in
on-going conversation. This suggests that turn-taking systems may well be a
shared cognitive infrastructure underlying all modern human languages, both
spoken and signed.
PMID- 25852595
TI - The precedence of syntax in the rapid emergence of human language in evolution as
defined by the integration hypothesis.
AB - Our core hypothesis is that the emergence of human language arose very rapidly
from the linking of two pre-adapted systems found elsewhere in the animal world
an expression system, found, for example, in birdsong, and a lexical system,
suggestively found in non-human primate calls (Miyagawa et al., 2013, 2014). We
challenge the view that language has undergone a series of gradual changes-or a
single preliminary protolinguistic stage-before achieving its full character. We
argue that a full-fledged combinatorial operation Merge triggered the integration
of these two pre-adapted systems, giving rise to a fully developed language. This
goes against the gradualist view that there existed a structureless,
protolinguistic stage, in which a rudimentary proto-Merge operation generated
internally flat words. It is argued that compounds in present-day language are a
fossilized form of this prior stage, a point which we will question.
PMID- 25852594
TI - Does long-term object priming depend on the explicit detection of object identity
at encoding?
AB - It is currently unclear whether objects have to be explicitly identified at
encoding for reliable behavioral long-term object priming to occur. We conducted
two experiments that investigated long-term object and non-object priming using a
selective-attention encoding manipulation that reduces explicit object
identification. In Experiment 1, participants either counted dots flashed within
an object picture (shallow encoding) or engaged in an animacy task (deep
encoding) at study, whereas, at test, they performed an object-decision task.
Priming, as measured by reaction times (RTs), was observed for both types of
encoding, and was of equivalent magnitude. In Experiment 2, non-object priming
(faster RTs for studied relative to unstudied non-objects) was also obtained
under the same selective-attention encoding manipulation as in Experiment 1, and
the magnitude of the priming effect was equivalent between experiments. In
contrast, we observed a linear decrement in recognition memory accuracy across
conditions (deep encoding of Experiment 1 > shallow encoding Experiment 1 >
shallow encoding of Experiment 2), suggesting that priming was not contaminated
by explicit memory strategies. We argue that our results are more consistent with
the identification/production framework than the perceptual/conceptual
distinction, and we conclude that priming of pictures largely ignored at encoding
can be subserved by the automatic retrieval of two types of instances: one at the
motor level and another at an object-decision level.
PMID- 25852596
TI - LIFESPAN: A tool for the computer-aided design of longitudinal studies.
AB - Researchers planning a longitudinal study typically search, more or less
informally, a multivariate space of possible study designs that include
dimensions such as the hypothesized true variance in change, indicator
reliability, the number and spacing of measurement occasions, total study time,
and sample size. The main search goal is to select a research design that best
addresses the guiding questions and hypotheses of the planned study while heeding
applicable external conditions and constraints, including time, money,
feasibility, and ethical considerations. Because longitudinal study selection
ultimately requires optimization under constraints, it is amenable to the general
operating principles of optimization in computer-aided design. Based on power
equivalence theory (MacCallum et al., 2010; von Oertzen, 2010), we propose a
computational framework to promote more systematic searches within the study
design space. Starting with an initial design, the proposed framework generates a
set of alternative models with equal statistical power to detect hypothesized
effects, and delineates trade-off relations among relevant parameters, such as
total study time and the number of measurement occasions. We present LIFESPAN
(Longitudinal Interactive Front End Study Planner), which implements this
framework. LIFESPAN boosts the efficiency, breadth, and precision of the search
for optimal longitudinal designs. Its initial version, which is freely available
at http://www.brandmaier.de/lifespan, is geared toward the power to detect
variance in change as specified in a linear latent growth curve model.
PMID- 25852598
TI - How to enhance the well-being of healthcare service providers and their patients?
A mindfulness proposal.
PMID- 25852597
TI - The neural substrates of response inhibition to negative information across
explicit and implicit tasks in GAD patients: electrophysiological evidence from
an ERP study.
AB - BACKGROUND: It has been established that the inability to inhibit a response to
negative stimuli is the genesis of anxiety. However, the neural substrates of
response inhibition to sad faces across explicit and implicit tasks in general
anxiety disorder (GAD) patients remain unclear. METHODS: Electrophysiological
data were recorded when subjects performed two modified emotional go/no-go tasks
in which neutral and sad faces were presented: one task was explicit (emotion
categorization), and the other task was implicit (gender categorization).
RESULTS: In the explicit task, electrophysiological evidence showed decreased
amplitudes of no-go/go difference waves at the N2 interval in the GAD group
compared to the control group. However, in the implicit task, the amplitudes of
no-go/go difference waves at the N2 interval showed a reversed trend. Source
localization analysis on no-go/N2 components revealed a decreased current source
density (CSD) in the right dorsal lateral prefrontal cortex in GAD individuals
relative to controls. In the implicit task, the left superior temporal gyrus and
the left inferior parietal lobe showed enhanced activation in GAD individuals and
may compensate for the dysfunction of the right dorsal lateral prefrontal cortex.
CONCLUSION: These findings indicated that the processing of response inhibition
to socially sad faces in GAD individuals was interrupted in the explicit task.
However, this processing was preserved in the implicit task. The neural
substrates of response inhibition to sad faces were dissociated between implicit
and explicit tasks.
PMID- 25852599
TI - Affective valence facilitates spatial detection on vertical axis: shorter time
strengthens effect.
AB - Affective concepts can be described in terms of space, which is known as the
valence-space metaphor. Previous studies have not investigated either the
specifics of this metaphor on the transverse and vertical axes or the time course
of this metaphoric association. With Chinese participants, we used a spatial cue
task to study the valence-space metaphor on the transverse (left-and-right;
Experiment 1A) and vertical (upper-and-lower; Experiment 1B) axes. After being
shown an affective word and asked to keep it in mind, the participants were given
a spatial target detection task. The results revealed that the metaphoric
association was only found on the vertical axis. More specifically, keeping a
positive word in mind facilitated the detection of the upper target, but no such
effect was found in the detection of the lower target. Furthermore, in Experiment
2, we manipulated the duration of time (100, 500, and 1000 ms) between the offset
of the affective word and the onset of the spatial target (i.e., interstimulus
intervals, ISI), to test the dynamic time course of the valence-space metaphor on
the vertical axis. The results showed that when ISI was 100 ms, keeping a
positive word in mind facilitated the detection of the upper target and keeping a
negative word in mind facilitated the detection of the lower target. However,
when the ISI was 500 or 1000 ms, keeping a positive word in mind facilitated the
detection of the upper target and no such effect was found in the detection of
the lower target, indicating that ISI might be important in the valence-space
metaphoric association. In sum, we found that the processing of affective valence
activated the vertical spatial axis but not the transverse axis. Further, the
association might be modulated by ISI, indicating that it may be related to
attention allocation.
PMID- 25852600
TI - Children's looking preference for biological motion may be related to an affinity
for mathematical chaos.
AB - Recognition of biological motion is pervasive in early child development.
Further, viewing the movement behavior of others is a primary component of a
child's acquisition of complex, robust movement repertoires, through imitation
and real-time coordinated action. We theorize that inherent to biological
movements are particular qualities of mathematical chaos and complexity. We
further posit that this character affords the rich and complex inter-dynamics
throughout early motor development. Specifically, we explored whether children's
preference for biological motion may be related to an affinity for mathematical
chaos. Cross recurrence quantification analysis (cRQA) was used to investigate
the coordination of gaze and posture with various temporal structures (periodic,
chaotic, and aperiodic) of the motion of an oscillating visual stimulus. Children
appear to competently perceive and respond to chaotic motion, both in rate (cRQA
percent determinism) and duration (cRQA-maxline) of coordination. We interpret
this to indicate that children not only recognize chaotic motion structures, but
also have a preference for coordination with them. Further, stratification of our
sample (by age) uncovers the suggestion that this preference may become refined
with age.
PMID- 25852601
TI - Predicting who takes music lessons: parent and child characteristics.
AB - Studies on associations between music training and cognitive abilities typically
focus on the possible benefits of music lessons. Recent research suggests,
however, that many of these associations stem from niche-picking tendencies,
which lead certain individuals to be more likely than others to take music
lessons, especially for long durations. Because the initial decision to take
music lessons is made primarily by a child's parents, at least at younger ages,
we asked whether individual differences in parents' personality predict young
children's duration of training. Children between 7 and 9 years of age (N = 170)
with varying amounts of music training completed a measure of IQ. Their parents
provided demographic information as well as ratings of their own and their
child's Big Five personality dimensions. Children's personality traits predicted
duration of music training even when demographic variables and intelligence were
held constant, replicating findings reported previously with 10- to 12-year-olds
and 17-year-olds. A novel finding was that parents' openness-to-experience
predicted children's duration of training, even when characteristics that
pertained to children (demographic variables, intelligence, and personality) were
controlled statistically. Our findings are indicative of passive and active gene
environment correlations, whereby genetic predispositions influence the
likelihood that a child will have certain experiences, such as music training.
PMID- 25852602
TI - Dreams as a source of supernatural agent concepts.
AB - We present a theory of the creativity of dreams as well as psychopathology of
religious delusions with respect to production of fundamental forms of religious
cognition-specifically supernatural agent (SA) cognitions. We suggest that dream
cognitions are particularly efficient at producing highly memorable and impactful
experiences with SAs because dreams involve three processes that are
prerequisites for the generation of god concepts: (1) mental simulations of
alternative realities, (2) theory of mind attributions to the extra-natural dream
characters and divine beings, and (3) attribution of ultimate value (exemplified
by 'good spirit beings'), and dis-value (exemplified by demonic monsters) to the
supernatural dream characters. Because prefrontal cortex is deactivated during
rapid eye movements (REM) sleep agentic impulses and internally generated ideas
are not reliably attributed to Self or dreamer. Instead an exaggerated degree of
agency is attributed to these supernatural dream characters who are then embedded
in stories in dreams and in myths of waking life which explain their supernatural
abilities. These dream-based SAs are salient characters that are processed in
sleep-related memory systems according to rules of Lleweelyn's ancient art of
memory model and therefore more easily remembered and reflected upon during
waking life. When REM sleep intrudes into waking consciousness, as is the case
with some forms of schizophrenia, religious delusions are more likely to emerge.
PMID- 25852603
TI - Evaluation of a differentiation model of preschoolers' executive functions.
AB - Despite the prominent role of executive functions in children's emerging
competencies, there remains debate regarding the structure and development of
executive functions. In an attempt to reconcile these discrepancies, a
differentiation model of executive function development was evaluated in the
early years using 6-month age groupings. Specifically, 281 preschoolers completed
measures of working memory, inhibition, and shifting. Results contradicted
suggestions that executive functions follow a single trajectory of progressive
separation in childhood, instead suggesting that these functions may undergo a
period of integration in the preschool years. These results highlight potential
problems with current practices and theorizing in executive function research.
PMID- 25852604
TI - Musical plus phonological input for young foreign language readers.
AB - Based on previous studies showing that phonological awareness is related to
reading abilities and that music training improves phonological processing, the
aim of the present study was to test for the efficiency of a new method for
teaching to read in a foreign language. Specifically, we tested the efficacy of a
phonological training program, with and without musical support that aimed at
improving early reading skills in 7-8-year-old Spanish children (n = 63) learning
English as a foreign language. Of interest was also to explore the impact of this
training program on working memory and decoding skills. To achieve these goals we
tested three groups of children before and after training: a control group, an
experimental group with phonological non-musical intervention (active control),
and an experimental group with musical intervention. Results clearly point to the
beneficial effects of the phonological teaching approach but the further impact
of the music support was not demonstrated. Moreover, while children in the music
group showed low musical aptitudes before training, they nevertheless performed
better than the control group. Therefore, the phonological training program with
and without music support seem to have significant effects on early reading
skills.
PMID- 25852605
TI - Are the deficits in navigational abilities present in the Williams syndrome
related to deficits in the backward inhibition?
AB - Williams syndrome (WS) is associated with a distinct profile of relatively
proficient skills within the verbal domain compared to the severe impairment of
visuo-spatial processing. Abnormalities in executive functions and deficits in
planning ability and spatial working memory have been described. However, to date
little is known about the influence of executive function deficits on
navigational abilities in WS. This study aimed at analyzing in WS individuals a
specific executive function, the backward inhibition (BI) that allows individuals
to flexibly adapt to continuously changing environments. A group of WS
individuals and a mental age- and gender-matched group of typically developing
children were subjected to three task-switching experiments requiring
visuospatial or verbal material to be processed. Results showed that WS
individuals exhibited clear BI deficits during visuospatial task-switching
paradigms and normal BI effect during verbal task-switching paradigm. Overall,
the present results suggest that the BI involvement in updating environment
representations during navigation may influence WS navigational abilities.
PMID- 25852606
TI - Impact on children of a parent with ALS: a case-control study.
AB - BACKGROUND: Numerous studies have explored how patients and their caregivers cope
with amyotrophic lateral sclerosis (ALS), but the literature completely lacks
research on the psychological impact of the disease on patients' children. The
aim of our study was to investigate the emotional and psychological impact of a
parent with ALS on school-age children and adolescents in terms of problem
behavior, adjustment, and personality characteristics. METHODS: The study
involved 23 children (mean age = 10.62 years, six females) with a parent
suffering from ALS, and both their parents. Children were matched for age,
gender, and birth-order with a control group of children with healthy parents.
They were administered the Youth Self Report (YSR) questionnaire and the
Rorschach Comprehensive System, and their healthy parent completed the Child
Behavior Checklist (CBCL). RESULTS: Findings clearly showed that, compared with
controls, children with a parent who had ALS had several clinically significant
adverse emotional and behavioral consequences, with emotional and behavioral
problems, internalizing problems, anxiety and depressive symptoms. Children of a
parent with ALS scored higher than controls for the Total Problems, Internalizing
Problems, Anxious/Depressed and Withdrawn/Depressed scales in the YSR. A relevant
percentage of children fell within the clinical range (42.9%) and borderline
range (28.6%) for Internalizing Problems. The Rorschach CS confirmed the
substantial impact of ALS in a parent on their offspring in terms of
internalizing behavior and depression, with adjustment difficulties,
psychological pain, and thought problems. CONCLUSION: Our findings indicate that
school-aged children and adolescents with a parent who has ALS are vulnerable and
carry a substantially higher risk of internalizing behavior, depressive symptoms,
and reactive problems than children with healthy parents. Families affected may
need support to cope with such an overwhelming disease.
PMID- 25852607
TI - Clinical TVA-based studies: a general review.
AB - In combination with whole report and partial report tasks, the theory of visual
attention (TVA) can be used to estimate individual differences in five basic
attentional parameters: the visual processing speed, the storage capacity of
visual short-term memory, the perceptual threshold, the efficiency of top-down
selectivity, and the spatial bias of attentional weighting. TVA-based assessment
has been used in about 30 studies to investigate attentional deficits in a range
of neurological and psychiatric conditions: (a) neglect and simultanagnosia, (b)
reading disturbances, (c) aging and neurodegenerative diseases, and most recently
(d) neurodevelopmental disorders. The article introduces TVA based assessment,
discusses its methodology and psychometric properties, and reviews the progress
made in each of the four research fields. The empirical results demonstrate the
general usefulness of TVA-based assessment for many types of clinical
neuropsychological research. The method's most important qualities are cognitive
specificity and theoretical grounding, but it is also characterized by good
reliability and sensitivity to minor deficits. The review concludes by pointing
to promising new areas for clinical TVA-based research.
PMID- 25852608
TI - Facial feedback affects valence judgments of dynamic and static emotional
expressions.
AB - The ability to judge others' emotions is required for the establishment and
maintenance of smooth interactions in a community. Several lines of evidence
suggest that the attribution of meaning to a face is influenced by the facial
actions produced by an observer during the observation of a face. However,
empirical studies testing causal relationships between observers' facial actions
and emotion judgments have reported mixed findings. This issue was investigated
by measuring emotion judgments in terms of valence and arousal dimensions while
comparing dynamic vs. static presentations of facial expressions. We presented
pictures and videos of facial expressions of anger and happiness. Participants (N
= 36) were asked to differentiate between the gender of faces by activating the
corrugator supercilii muscle (brow lowering) and zygomaticus major muscle (cheek
raising). They were also asked to evaluate the internal states of the stimuli
using the affect grid while maintaining the facial action until they finished
responding. The cheek raising condition increased the attributed valence scores
compared with the brow-lowering condition. This effect of facial actions was
observed for static as well as for dynamic facial expressions. These data suggest
that facial feedback mechanisms contribute to the judgment of the valence of
emotional facial expressions.
PMID- 25852609
TI - Starting off on the right foot: strong right-footers respond faster with the
right foot to positive words and with the left foot to negative words.
AB - Recent studies have provided evidence for an association between valence and
left/right modulated by handedness, which is predicted by the body-specificity
hypothesis (Casasanto, 2009) and also reflected in response times. We
investigated whether such a response facilitation can also be observed with foot
responses. Right-footed participants classified positive and negative words
according to their valence by pressing a key with their left or right foot. A
significant interaction between valence and foot only emerged in the by-items
analysis. However, when dividing participants into two groups depending on the
strength of their footedness, an interaction between valence and left/right was
observed for strong right-footers, who responded faster with the right foot to
positive words, and with the left foot to negative words. No interaction emerged
for weak right-footers. The results strongly support the assumption that fluency
lies at the core of the association between valence and left/right.
PMID- 25852610
TI - Limitless capacity: a dynamic object-oriented approach to short-term memory.
AB - The notion of capacity-limited processing systems is a core element of cognitive
accounts of limited and variable performance, enshrined within the short-term
memory construct. We begin with a detailed critical analysis of the conceptual
bases of this view and argue that there are fundamental problems - ones that go
to the heart of cognitivism more generally - that render it untenable. In place
of limited capacity systems, we propose a framework for explaining performance
that focuses on the dynamic interplay of three aspects of any given setting: the
particular task that must be accomplished, the nature and form of the material
upon which the task must be performed, and the repertoire of skills and
perceptual-motor functions possessed by the participant. We provide empirical
examples of the applications of this framework in areas of performance typically
accounted for by reference to capacity-limited short-term memory processes.
PMID- 25852611
TI - The intelligibility of r or r (2) as an effect size statistic: dichotomous
variables.
PMID- 25852612
TI - Methodological aspects to be considered when measuring the approximate number
system (ANS) - a research review.
AB - According to a dominant view, the approximate number system (ANS) is the
foundation of symbolic math abilities. Due to the importance of math abilities
for education and career, a lot of research focuses on the investigation of the
ANS and its relationship with math performance. However, the results are
inconsistent. This might be caused by studies differing greatly regarding the
operationalization of the ANS (i.e., tasks, dependent variables). Moreover, many
methodological aspects vary from one study to the next. In the present review, we
discuss commonly used ANS tasks and dependent variables regarding their
theoretical foundation and psychometric features. We argue that the inconsistent
findings concerning the relationship between ANS acuity and math performance may
be partially explained by differences in reliability. Furthermore, this review
summarizes methodological aspects of ANS tasks having important impacts on the
results, including stimulus range, visual controls, presentation duration of the
stimuli and feedback. Based on this review, we give methodological
recommendations on how to assess the ANS most reliably and most validly. All
important methodological aspects to be considered when designing an ANS task or
comparing results of different studies are summarized in two practical
checklists.
PMID- 25852613
TI - Attachment style predicts affect, cognitive appraisals, and social functioning in
daily life.
AB - The way in which attachment styles are expressed in the moment as individuals
navigate their real-life settings has remained an area largely untapped by
attachment research. The present study examined how adult attachment styles are
expressed in daily life using experience sampling methodology (ESM) in a sample
of 206 Spanish young adults. Participants were administered the Attachment Style
Interview (ASI) and received personal digital assistants that signaled them
randomly eight times per day for 1 week to complete questionnaires about their
current experiences and social context. As hypothesized, participants' momentary
affective states, cognitive appraisals, and social functioning varied in
meaningful ways as a function of their attachment style. Individuals with an
anxious attachment, as compared with securely attached individuals, endorsed
experiences that were congruent with hyperactivating tendencies, such as higher
negative affect, stress, and perceived social rejection. By contrast, individuals
with an avoidant attachment, relative to individuals with a secure attachment,
endorsed experiences that were consistent with deactivating tendencies, such as
decreased positive states and a decreased desire to be with others when alone.
Furthermore, the expression of attachment styles in social contexts was shown to
be dependent upon the subjective appraisal of the closeness of social contacts,
and not merely upon the presence of social interactions. The findings support the
ecological validity of the ASI and the person-by-situation character of
attachment theory. Moreover, they highlight the utility of ESM for investigating
how the predictions derived from attachment theory play out in the natural flow
of real life.
PMID- 25852614
TI - Enhancing behavioral change with motivational interviewing: a case study in a
Cardiac Rehabilitation Unit.
AB - BACKGROUND: Psychological interventions in cardiac rehabilitation programs appear
relevant in as much they significantly contribute to achieve the goals of
rehabilitation, to reduce the risk of relapses and to improve patients' adherence
to therapy. To this aim, motivational interviewing (MI) has shown promising
results in improving motivation to change and individuals' confidence in their
ability to do so. OBJECTIVE: The purpose of this article is to integrate theory
with practice by describing a three-session case scenario. It illustrates how
MI's skills and strategies can be used to enhance heart-healthy habits. MI may be
synergistic with other treatment approaches and it is used here in conjunction
with brief strategic therapy. CONCLUSION: By the use of MI principles and
techniques, the patient reported an increase in his motivation and ability to
change, developing a post discharge plan that incorporates self-care behaviors.
CLINICAL IMPLICATIONS: MI may be effective in motivating and facilitating health
behavior change among obese patients suffering from heart failure.
PMID- 25852615
TI - Absolute and proportional measures of potential markers of rehearsal, and their
implications for accounts of its development.
AB - Previous studies of the development of phonological similarity and word length
effects in children have shown that these effects are small or absent in young
children, particularly when measured using visual presentation of the memoranda.
This has often been taken as support for the view that young children do not
rehearse. The current paper builds on recent evidence that instead suggests that
absent phonological similarity and word length effects in young children reflects
the same proportional cost of these effects in children of all ages. Our aims are
to explore the conditions under which this proportional scaling account can
reproduce existing developmental data, and in turn suggest ways that future
studies might measure and model phonological similarity and word length effects
in children. To that end, we first fit a single mathematical function through
previously reported data that simultaneously captures absent and negative
proportional effects of phonological similarity in young children plus constant
proportional similarity effects in older children. This developmental function
therefore provides the benchmark that we seek to re-produce in a series of
subsequent simulations that test the proportional scaling account. These
simulations reproduce the developmental function well, provided that they take
into account the influence of floor effects and of measurement error. Our
simulations suggest that future empirical studies examining these effects in the
context of the development of rehearsal need to take into account proportional
scaling. They also provide a demonstration of how proportional costs can be
explored, and of the possible developmental functions associated with such an
analysis.
PMID- 25852616
TI - Many faces of bankers' identity: how (not) to study dishonesty.
PMID- 25852617
TI - The (un)suitability of modern liquid crystal displays (LCDs) for vision research.
AB - Psychophysical and physiological studies of vision have traditionally used
cathode ray tube (CRT) monitors to present stimuli. These monitors are no longer
easily available, and liquid crystal display (LCD) technology is continually
improving; therefore, we characterized a number of LCD monitors to determine if
newer models are suitable replacements for CRTs in the laboratory. We compared
the spatial and temporal characteristics of a CRT with five LCDs, including
monitors designed with vision science in mind (ViewPixx and Display++),
"prosumer" gaming monitors, and a consumer-grade LCD. All monitors had sufficient
contrast, luminance range and reliability to support basic vision experiments
with static images. However, the luminance of all LCDs depended strongly on
viewing angle, which in combination with the poor spatial uniformity of all
monitors except the VPixx, caused up to 80% drops in effective luminance in the
periphery during central fixation. Further, all monitors showed significant
spatial dependence, as the luminance of one area was modulated by the luminance
of other areas. These spatial imperfections are most pronounced for experiments
that use large or peripheral visual stimuli. In the temporal domain, the gaming
LCDs were unable to generate reliable luminance patterns; one was unable to reach
the requested luminance within a single frame whereas in the other the luminance
of one frame affected the luminance of the next frame. The VPixx and Display++
were less affected by these problems, and had good temporal properties provided
stimuli were presented for 2 or more frames. Of the consumer-grade and gaming
displays tested, and if problems with spatial uniformity are taken into account,
the Eizo FG2421 is the most suitable alternative to CRTs. The specialized
ViewPixx performed best among all the tested LCDs, followed closely by the
Display++; both are good replacements for a CRT, provided their spatial
imperfections are considered.
PMID- 25852618
TI - The self in conflict: actors and agency in the mediated sequential Simon task.
AB - Executive control refers to the ability to withstand interference in order to
achieve task goals. The effect of conflict adaptation describes that after
experiencing interference, subsequent conflict effects are weaker. However,
changes in the source of conflict have been found to disrupt conflict adaptation.
Previous studies indicated that this specificity is determined by the degree to
which one source causes episodic retrieval of a previous source. A virtual
reality version of the Simon task was employed to investigate whether changes in
a visual representation of the self would similarly affect conflict adaptation.
Participants engaged in a mediated Simon task via 3D "avatar" models that either
mirrored the participants' movements, or were presented statically. A retrieval
cue was implemented as the identity of the avatar: switching it from a male to a
female avatar was expected to disrupt the conflict adaptation effect (CAE). The
results show that only in static conditions did the CAE depend on the avatar
identity, while in dynamic conditions, changes did not cause disruption. We also
explored the effect of conflict and adaptation on the degree of movement made
with the task-irrelevant hand and replicated the reaction time pattern. The
findings add to earlier studies of source-specific conflict adaptation by showing
that a visual representation of the self in action can provide a cue that
determines episodic retrieval. Furthermore, the novel paradigm is made openly
available to the scientific community and is described in its significance for
studies of social cognition, cognitive psychology, and human-computer
interaction.
PMID- 25852619
TI - Commentary on: "The body social: an enactive approach to the self". A tool for
merging bodily and social self in immobile individuals.
PMID- 25852620
TI - What you see is what you get: webcam placement influences perception and social
coordination.
AB - Building on a well-established link between elevation and social power, we
demonstrate that-when perceptual information is limited-subtle visual cues can
shape people's representations of others and, in turn, alter strategic social
behavior. A cue to elevation (unrelated to physical size) provided by the
placement of web cameras in a video chat biased individuals' perceptions of a
partner's height (Experiment 1) and shaped the extent to which they made
decisions in their own self-interest: participants tended to coordinate their
behavior in a manner that benefitted the preferences of a partner pictured from a
low camera angle during a game of asymmetric coordination (Experiment 2). Our
results suggest that people are vulnerable to the influence of a limited
viewpoint when forming representations of others in a manner that shapes their
strategic choices.
PMID- 25852621
TI - Problematic assumptions have slowed down depression research: why symptoms, not
syndromes are the way forward.
AB - Major depression (MD) is a highly heterogeneous diagnostic category. Diverse
symptoms such as sad mood, anhedonia, and fatigue are routinely added to an
unweighted sum-score, and cutoffs are used to distinguish between depressed
participants and healthy controls. Researchers then investigate outcome variables
like MD risk factors, biomarkers, and treatment response in such samples. These
practices presuppose that (1) depression is a discrete condition, and that (2)
symptoms are interchangeable indicators of this latent disorder. Here I review
these two assumptions, elucidate their historical roots, show how deeply
engrained they are in psychological and psychiatric research, and document that
they contrast with evidence. Depression is not a consistent syndrome with clearly
demarcated boundaries, and depression symptoms are not interchangeable indicators
of an underlying disorder. Current research practices lump individuals with very
different problems into one category, which has contributed to the remarkably
slow progress in key research domains such as the development of efficacious
antidepressants or the identification of biomarkers for depression. The recently
proposed network framework offers an alternative to the problematic assumptions.
MD is not understood as a distinct condition, but as heterogeneous symptom
cluster that substantially overlaps with other syndromes such as anxiety
disorders. MD is not framed as an underlying disease with a number of equivalent
indicators, but as a network of symptoms that have direct causal influence on
each other: insomnia can cause fatigue which then triggers concentration and
psychomotor problems. This approach offers new opportunities for constructing an
empirically based classification system and has broad implications for future
research.
PMID- 25852622
TI - Shifting goals: effects of active and observational experience on infants'
understanding of higher order goals.
AB - Action perception links have been argued to support the emergence of action
understanding, but their role in infants' perception of distal goals has not been
fully investigated. The current experiments address this issue. During the
development of means-end actions, infants shift their focus from the means of the
action to the distal goal. In Experiment One, we evaluated whether this same
shift in attention (from the means to the distal goal) when learning to produce
multi-step actions is reflected in infants' perception of others' means-end
actions. Eight-months-old infants underwent active training in means-end action
production and their subsequent analysis of an observed means-end action was
assessed in a visual habituation paradigm. Infants' degree of success in the
training paradigm was related to their subsequent interpretation of the observed
action as directed at the means versus the distal goal. In Experiment Two,
observational and control manipulations provided evidence that these effects
depended on the infants' active engagement in the means-end actions. These
results suggest that the processes that give rise to means-end structure in
infants' motor behavior also support the emergence of means-end structure in
their analysis of others' goals.
PMID- 25852623
TI - Working memory differences in long-distance dependency resolution.
AB - There is a wealth of evidence showing that increasing the distance between an
argument and its head leads to more processing effort, namely, locality effects;
these are usually associated with constraints in working memory (DLT: Gibson,
2000; activation-based model: Lewis and Vasishth, 2005). In SOV languages,
however, the opposite effect has been found: antilocality (see discussion in Levy
et al., 2013). Antilocality effects can be explained by the expectation-based
approach as proposed by Levy (2008) or by the activation-based model of sentence
processing as proposed by Lewis and Vasishth (2005). We report an eye-tracking
and a self-paced reading study with sentences in Spanish together with measures
of individual differences to examine the distinction between expectation- and
memory-based accounts, and within memory-based accounts the further distinction
between DLT and the activation-based model. The experiments show that (i)
antilocality effects as predicted by the expectation account appear only for high
capacity readers; (ii) increasing dependency length by interposing material that
modifies the head of the dependency (the verb) produces stronger facilitation
than increasing dependency length with material that does not modify the head;
this is in agreement with the activation-based model but not with the expectation
account; and (iii) a possible outcome of memory load on low-capacity readers is
the increase in regressive saccades (locality effects as predicted by memory
based accounts) or, surprisingly, a speedup in the self-paced reading task; the
latter consistent with good-enough parsing (Ferreira et al., 2002). In sum, the
study suggests that individual differences in working memory capacity play a role
in dependency resolution, and that some of the aspects of dependency resolution
can be best explained with the activation-based model together with a prediction
component.
PMID- 25852624
TI - The relational responding task: toward a new implicit measure of beliefs.
AB - We introduce the Relational Responding Task (RRT) as a tool for capturing beliefs
at the implicit level. Flemish participants were asked to respond as if they
believed that Flemish people are more intelligent than immigrants (e.g., respond
"true" to the statement "Flemish people are wiser than immigrants") or to respond
as if they believed that immigrants are more intelligent than Flemish people
(e.g., respond "true" to the statement "Flemish people are dumber than
immigrants"). The difference in performance between these two tasks correlated
with ratings of the extent to which participants explicitly endorsed the belief
that Flemish people are more intelligent than immigrants and with questionnaire
measures of subtle and blatant racism. The current study provides a first step
toward validating RRT effects as a viable measure of implicit beliefs.
PMID- 25852625
TI - Grounding context in face processing: color, emotion, and gender.
AB - In recent years, researchers have become interested in the way that the affective
quality of contextual information transfers to a perceived target. We therefore
examined the effect of a red (vs. green, mixed red/green, and achromatic)
background - known to be valenced - on the processing of stimuli that play a key
role in human interactions, namely facial expressions. We also examined whether
the valenced-color effect can be modulated by gender, which is also known to be
valenced. Female and male adult participants performed a categorization task of
facial expressions of emotion in which the faces of female and male posers
expressing two ambiguous emotions (i.e., neutral and surprise) were presented
against the four different colored backgrounds. Additionally, this task was
completed by collecting subjective ratings for each colored background in the
form of five semantic differential scales corresponding to both discrete and
dimensional perspectives of emotion. We found that the red background resulted in
more negative face perception than the green background, whether the poser was
female or male. However, whereas this valenced-color effect was the only effect
for female posers, for male posers, the effect was modulated by both the nature
of the ambiguous emotion and the decoder's gender. Overall, our findings offer
evidence that color and gender have a common valence-based dimension.
PMID- 25852627
TI - Commentary on: "Agency, time, and causality".
PMID- 25852626
TI - Semantic memory as the root of imagination.
PMID- 25852628
TI - Prospect theory and body mass: characterizing psychological parameters for weight
related risk attitudes and weight-gain aversion.
AB - We developed a novel decision-making paradigm that allows us to apply prospect
theory in behavioral economics to body mass. 67 healthy young adults completed
self-report measures and two decision-making tasks for weight-loss, as well as
for monetary rewards. We estimated risk-related preference and loss aversion
parameters for each individual, separately for weight-loss and monetary rewards
choice data. Risk-seeking tendency for weight-loss was positively correlated with
body mass index in individuals who desired to lose body weight, whereas the risk
seeking for momentary rewards was not. Risk-seeking for weight-loss was
correlated to excessive body shape preoccupations, while aversion to weight-gain
was correlated with self-reports of behavioral involvement for successful weight
loss. We demonstrated that prospect theory can be useful in explaining the
decision-making process related to body mass. Applying prospect theory is
expected to advance our understanding of decision-making mechanisms in obesity,
which might prove helpful for improving healthy choices.
PMID- 25852629
TI - The processing of raising and nominal control: an eye-tracking study.
AB - According to some views of sentence processing, the memory retrieval processes
involved in dependency formation may differ as a function of the type of
dependency involved. For example, using closely matched materials in a single
experiment, Dillon et al. (2013) found evidence for retrieval interference in
subject-verb agreement, but not in reflexive-antecedent agreement. We report four
eye-tracking experiments that examine examine reflexive-antecedent dependencies,
combined with raising (e.g., "John seemed to Tom to be kind to himself..."), or
nominal control (e.g., "John's agreement with Tom to be kind to himself..."). We
hypothesized that dependencies involving raising would (a) be processed more
quickly, and (b) be less subject to retrieval interference, relative to those
involving nominal control. This is due to the fact that the interpretation of
raising is structurally constrained, while the interpretation of nominal control
depends crucially on lexical properties of the control nominal. The results
showed evidence of interference when the reflexive-antecedent dependency was
mediated by raising or nominal control, but very little evidence that could be
interpreted in terms of interference for direct reflexive-antecedent dependencies
that did not involve raising or control. However, there was no evidence either
for greater interference, or for quicker dependency formation, for raising than
for nominal control.
PMID- 25852630
TI - Testing normative and self-appraisal feedback in an online slot-machine pop-up in
a real-world setting.
AB - Over the last few years, there have been an increasing number of gaming operators
that have incorporated on-screen pop-up messages while gamblers play on slot
machines and/or online as one of a range of tools to help encourage responsible
gambling. Coupled with this, there has also been an increase in empirical
research into whether such pop-up messages are effective, particularly in
laboratory settings. However, very few studies have been conducted on the utility
of pop-up messages in real-world gambling settings. The present study
investigated the effects of normative and self-appraisal feedback in a slot
machine pop-up message compared to a simple (non-enhanced) pop-up message. The
study was conducted in a real-world gambling environment by comparing the
behavioral tracking data of two representative random samples of 800,000 gambling
sessions (i.e., 1.6 million sessions in total) across two conditions (i.e.,
simple pop-up message versus an enhanced pop-up message). The results indicated
that the additional normative and self-appraisal content doubled the number of
gamblers who stopped playing after they received the enhanced pop-up message
(1.39%) compared to the simple pop-up message (0.67%). The data suggest that pop
up messages influence only a small number of gamblers to cease long playing
sessions and that enhanced messages are slightly more effective in helping
gamblers to stop playing in-session.
PMID- 25852631
TI - Bench-to-Bedside and Bedside Back to the Bench; Seeking a Better Understanding of
the Acute Pathophysiological Process in Severe Traumatic Brain Injury.
AB - Despite substantial investments, traumatic brain injury (TBI) remains one of the
major disorders that lack specific pharmacotherapy. To a substantial degree, this
situation is due to lack of understanding of the pathophysiological process of
the disease. Experimental TBI research offers controlled, rapid, and cost
effective means to identify the pathophysiology but translating experimental
findings into clinical practice can be further improved by using the same or
similar outcome measures and clinically relevant time points. The pathophysiology
during the acute phase of severe TBI is especially poorly understood. In this
Mini review, I discuss some of the incongruences between current clinical
practices and needs versus information provided by experimental TBI research as
well as the benefits of designing animal experiments with translation into
clinical practice in mind.
PMID- 25852633
TI - Ubiquitin carboxy-terminal hydrolase-l1 as a serum neurotrauma biomarker for
exposure to occupational low-level blast.
AB - Repeated exposure to low-level blast is a characteristic of a few select
occupations and there is concern that such occupational exposures present risk
for traumatic brain injury. These occupations include specialized military and
law enforcement units that employ controlled detonation of explosive charges for
the purpose of tactical entry into secured structures. The concern for negative
effects from blast exposure is based on rates of operator self-reported headache,
sleep disturbance, working memory impairment, and other concussion-like symptoms.
A challenge in research on this topic has been the need for improved assessment
tools to empirically evaluate the risk associated with repeated exposure to blast
overpressure levels commonly considered to be too low in magnitude to cause acute
injury. Evaluation of serum-based neurotrauma biomarkers provides an objective
measure that is logistically feasible for use in field training environments.
Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has
some empirical support and was evaluated in this study. We used daily blood draws
to examine acute change in UCH-L1 among 108 healthy military personnel who were
exposed to repeated low-level blast across a 2-week period. These research
volunteers also wore pressure sensors to record blast exposures, wrist actigraphs
to monitor sleep patterns, and completed daily behavioral assessments of
symptomology, postural stability, and neurocognitive function. UCH-L1 levels were
elevated as a function of participating in the 2-week training with explosives,
but the correlation of UCH-L1 elevation and blast magnitude was weak and
inconsistent. Also, UCH-L1 elevations did not correlate with deficits in
behavioral measures. These results provide some support for including UCH-L1 as a
measure of central nervous system effects from exposure to low-level blast.
However, the weak relation observed suggests that additional indicators of blast
effect are needed.
PMID- 25852634
TI - The Role of fMRI to Assess Plasticity of the Motor System in MS.
PMID- 25852632
TI - Vascular and inflammatory factors in the pathophysiology of blast-induced brain
injury.
AB - Blast-related traumatic brain injury (TBI) has received much recent attention
because of its frequency in the conflicts in Iraq and Afghanistan. This renewed
interest has led to a rapid expansion of clinical and animal studies related to
blast. In humans, high-level blast exposure is associated with a prominent
hemorrhagic component. In animal models, blast exerts a variety of effects on the
nervous system including vascular and inflammatory effects that can be seen with
even low-level blast exposures which produce minimal or no neuronal pathology.
Acutely, blast exposure in animals causes prominent vasospasm and decreased
cerebral blood flow along with blood-brain barrier breakdown and increased
vascular permeability. Besides direct effects on the central nervous system,
evidence supports a role for a thoracically mediated effect of blast; whereby,
pressure waves transmitted through the systemic circulation damage the brain.
Chronically, a vascular pathology has been observed that is associated with
alterations of the vascular extracellular matrix. Sustained microglial and
astroglial reactions occur after blast exposure. Markers of a central and
peripheral inflammatory response are found for sustained periods after blast
injury and include elevation of inflammatory cytokines and other inflammatory
mediators. At low levels of blast exposure, a microvascular pathology has been
observed in the presence of an otherwise normal brain parenchyma, suggesting that
the vasculature may be selectively vulnerable to blast injury. Chronic immune
activation in brain following vascular injury may lead to neurobehavioral changes
in the absence of direct neuronal pathology. Strategies aimed at preventing or
reversing vascular damage or modulating the immune response may improve the
chronic neuropsychiatric symptoms associated with blast-related TBI.
PMID- 25852635
TI - Measuring Gray Matter and White Matter Damage in MS: Why This is Not Enough.
PMID- 25852636
TI - Left atrial septal pouch in cryptogenic stroke.
AB - BACKGROUND: The left atrial septal pouch (LASP), an anatomic variant of the
interatrial septum, has uncertain clinical significance. We examined the
association between LASP and ischemic stroke subtypes in patients undergoing
transesophageal echocardiography (TEE). METHODS: We determined the prevalence of
LASP among consecutive patients who underwent TEE at our institution. Patients
identified with ischemic strokes were further evaluated for stroke subtype using
standard and modified criteria from the Trial of Org 10172 in Acute Stroke
Treatment (TOAST). We compared the prevalence of LASP in ischemic stroke,
cryptogenic stroke, and non-stroke patients using prevalence ratios (PR).
RESULTS: The mean age of all 212 patients (including stroke and non-stroke
patients) was 57 years. The overall prevalence of LASP was 17% (n = 35). Of the
75 patients who were worked-up for stroke at our institution during study period,
we classified 31 as cryptogenic using standard TOAST criteria. The prevalence of
LASP among cryptogenic stroke patients (using standard and modified TOAST
criteria) was increased compared to the prevalence among other ischemic stroke
patients (26 vs. 9%, p = 0.06; PR = 1.8, 95% CI = 1.1-3.1, and 30 vs. 10%, p =
0.04; PR = 2.2, 95% CI = 1.2-4.1, respectively). CONCLUSION: In this population
of relatively young patients, prevalence of LASP was increased in cryptogenic
stroke compared to stroke patients of other subtypes. These findings suggest LASP
is associated with cryptogenic stroke, which should be verified by future large
scale studies.
PMID- 25852637
TI - Horizontal Eye Position Affects Measured Vertical VOR Gain on the Video Head
Impulse Test.
AB - BACKGROUND/HYPOTHESIS: With the video head impulse test (vHIT), the vertical VOR
gain is defined as (vertical eye velocity/vertical head velocity), but
compensatory eye movements to vertical canal stimulation usually have a torsional
component. To minimize the contribution of torsion to the eye movement
measurement, the horizontal gaze direction should be directed 40 degrees from
straight ahead so it is in the plane of the stimulated canal plane pair.
HYPOTHESIS: as gaze is systematically moved horizontally away from canal plane
alignment, the measured vertical VOR gain should decrease. STUDY DESIGN: Ten
healthy subjects, with vHIT measuring vertical eye movement to head impulses in
the plane of the left anterior-right posterior (LARP) canal plane, with gaze at
one of five horizontal gaze positions [40 degrees (aligned with the LARP plane),
20 degrees , 0 degrees , -20 degrees , -40 degrees ]. METHODS: Every head impulse
was in the LARP plane. The compensatory eye movement was measured by the vHIT
prototype system. The one operator delivered every impulse. RESULTS: The canal
stimulus remained identical across trials, but the measured vertical VOR gain
decreased as horizontal gaze angle was shifted away from alignment with the LARP
canal plane. CONCLUSION: In measuring vertical VOR gain with vHIT the horizontal
gaze angle should be aligned with the canal plane under test.
PMID- 25852638
TI - Neuroplasticity and motor rehabilitation in multiple sclerosis.
PMID- 25852639
TI - Cannabinoid CB1 Receptor Agonists Do Not Decrease, but may Increase Acoustic
Trauma-Induced Tinnitus in Rats.
AB - Tinnitus has been suggested to arise from neuronal hyperactivity in auditory
areas of the brain, and anti-epileptic drugs are sometimes used to provide relief
from tinnitus. Recently, the anti-epileptic properties of the cannabinoid drugs
have gained increasing interest; however, the use of cannabinoids as a form of
treatment for tinnitus is controversial. In this study, we tested whether a
combination of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD),
delivered in a 1:1 ratio, could affect tinnitus perception in a rat model of
acoustic trauma-induced tinnitus. Following sham treatment or acoustic trauma,
the animals were divided into the following groups: (1) sham (i.e., no acoustic
trauma) with vehicle treatment; (2) sham with drug treatment (i.e., delta-9-THC +
CBD); (3) acoustic trauma-exposed exhibiting tinnitus, with drug treatment; and
(4) acoustic trauma-exposed exhibiting no tinnitus, with drug treatment. The
animals received either the vehicle or the cannabinoid drugs every day, 30 min
before the tinnitus behavioral testing. Acoustic trauma caused a significant
increase in the auditory brainstem response (ABR) thresholds in the exposed
animals, indicating hearing loss; however, there was a partial recovery over 6
months. Acoustic trauma did not always result in tinnitus; however, among those
that did exhibit tinnitus, some of them had tinnitus at multiple frequencies
while others had it only at a single frequency. The cannabinoids significantly
increased the number of tinnitus animals in the exposed-tinnitus group, but not
in the sham group. The results suggest that cannabinoids may promote the
development of tinnitus, especially when there is pre-existing hearing damage.
PMID- 25852640
TI - Biochemical response to hyperbaric oxygen treatment of a transhemispheric
penetrating cerebral gunshot injury.
AB - Hyperbaric oxygen (HBO) therapy has been suggested a treatment option in order to
reduce the development of secondary insults succeeding traumatic brain injury.
This case report studied the course of a 23-year-old gentleman with a close range
transhemispheric gunshot wound. The biochemical parameters, using a multi-modal
monitoring in the neuro-intensive care unit, improved following HBO treatment.
PMID- 25852641
TI - Demyelinating and thrombotic diseases of the central nervous system: common
pathogenic and triggering factors.
PMID- 25852642
TI - Ethnic differences in bone health.
AB - There are differences in bone health between ethnic groups in both men and in
women. Variations in body size and composition are likely to contribute to
reported differences. Most studies report ethnic differences in areal bone
mineral density (aBMD), which do not consistently parallel ethnic patterns in
fracture rates. This suggests that other parameters beside aBMD should be
considered when determining fracture risk between and within populations,
including other aspects of bone strength: bone structure and microarchitecture,
as well as muscle strength (mass, force generation, anatomy) and fat mass. We
review what is known about differences in bone-densitometry-derived outcomes
between ethnic groups and the extent to which they account for the differences in
fracture risk. Studies are included that were published primarily between 1994
and 2014. A "one size fits all approach" should definitely not be used to
understand better ethnic differences in fracture risk.
PMID- 25852643
TI - Diabetes, diet-health behavior, and obesity.
AB - High-quality diets play an important role in diabetes prevention. Appropriate
dietary adherence can improve insulin sensitivity and glycemic control, and thus
contribute to lifestyle improvement. However, previous research suggests that
dietary adherence is arguably among the most difficult cornerstones of diabetes
management. The objectives of this study are (1) to estimate whether and to what
extent individuals diagnosed with diabetes show significant differences in diet
quality [healthy eating index (HEI)] compared to healthy individuals, (2) to
quantify whether and to what extent diabetics experience significantly higher
outcomes of body mass index (BMI), and (3) to estimate whether and to what extent
dietary supplementation impacts diabetes patient's diet quality and/or BMI
outcomes. We use data from the 2007-2008 U.S. National Health and Nutrition
Examination Survey (NHANES). The NHANES is the primary, randomized, and
nationally representative survey used to assess the health and nutritional status
in the U.S. We apply propensity score matching (PSM) to account for selection
bias and endogeneity between self-reported diet and health behavir (treatment)
and BMI outcomes. We control for an individual's BMI as to capture the impact of
past dietary behavior in its impact on HEI. Matching results suggest that regular
dietary supplement consumption is associated with significant lower BMI outcomes
of almost 1 kg/m(2). The close relationship between diabetes and obesity has been
at the center of the diet-health policy debate across Canada and the U.S.
Knowledge about this linkage may help to improve the understanding of the factors
that impact dietary choices and their overall health outcomes, which may lead to
a more efficient and effective promotion of dietary guidelines, healthy food
choices, and targeted consumer health and lifestyle policies.
PMID- 25852645
TI - Ubiquitin-fold modifier 1 acts as a positive regulator of breast cancer.
AB - Estrogen receptor-alpha (ERalpha) is a steroid hormone-sensitive transcription
factor that plays a critical role in development of breast cancer. The binding of
estrogen to ERalpha triggers the recruitment of transcriptional co-activators as
well as chromatin remodeling factors to estrogen-responsive elements (ERE) of
ERalpha target genes. This process is tightly associated with post-translational
modifications (PTMs) of ERalpha and its co-activators for promotion of
transcriptional activation, which leads to proliferation of a large subset of
breast tumor cells. These PTMs include phosphorylation, acetylation, methylation,
and conjugation by ubiquitin and ubiquitin-like proteins. Ubiquitin-fold modifier
1 (UFM1), one of ubiquitin-like proteins, has recently been shown to be ligated
to activating signal co-integrator 1 (ASC1), which acts as a transcriptional co
activator of nuclear receptors. Here, we discuss the mechanistic connection
between ASC1 modification by UFM1 and ERalpha transactivation, and highlight how
the interplay of these processes is involved in development of breast cancer. We
also discuss potential use of UFM1-conjugating system as therapeutic targets
against not only breast cancer but also other nuclear receptor-mediated cancers.
PMID- 25852646
TI - Nuclear progestin receptor (pgr) knockouts in zebrafish demonstrate role for pgr
in ovulation but not in rapid non-genomic steroid mediated meiosis resumption.
AB - Progestins, progesterone derivatives, are the most critical signaling steroid for
initiating final oocyte maturation (FOM) and ovulation, in order to advance fully
grown immature oocytes to become fertilizable eggs in basal vertebrates. It is
well-established that progestin induces FOM at least partly through a membrane
receptor and a non-genomic steroid signaling process, which precedes progestin
triggered ovulation that is mediated through a nuclear progestin receptor (Pgr)
and genomic signaling pathway. To determine whether Pgr plays a role in a non
genomic signaling mechanism during FOM, we knocked out Pgr in zebrafish using
transcription activator-like effector nucleases (TALENs) and studied the oocyte
maturation phenotypes of Pgr knockouts (Pgr-KOs). Three TALENs-induced mutant
lines with different frame shift mutations were generated. Homozygous Pgr-KO
female fish were all infertile while no fertility effects were evident in
homozygous Pgr-KO males. Oocytes developed and underwent FOM normally in vivo in
homozygous Pgr-KO female compared to the wild-type controls, but these mature
oocytes were trapped within the follicular cells and failed to ovulate from the
ovaries. These oocytes also underwent normal germinal vesicle breakdown (GVBD)
and FOM in vitro, but failed to ovulate even after treatment with human chronic
gonadotropin (HCG) or progestin (17alpha,20beta-dihydroxyprogesterone or DHP),
which typically induce FOM and ovulation in wild-type oocytes. The results
indicate that anovulation and infertility in homozygous Pgr-KO female fish was,
at least in part, due to a lack of functional Pgr-mediated genomic progestin
signaling in the follicular cells adjacent to the oocytes. Our study of Pgr-KO
supports previous results that demonstrate a role for Pgr in steroid-dependent
genomic signaling pathways leading to ovulation, and the first convincing
evidence that Pgr is not essential for initiating non-genomic progestin signaling
and triggering of meiosis resumption.
PMID- 25852644
TI - Manipulating the circadian and sleep cycles to protect against metabolic disease.
AB - Modernization of human society parallels an epidemic of metabolic disorders
including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses
another important challenge to our metabolic health. Recent research under both
laboratory and epidemiological settings has indicated that abnormal temporal
organization of sleep and wakeful activities including food intake is a
significant risk factor for metabolic disease. The circadian clock system is our
intrinsic biological timer that regulates internal rhythms such as the sleep/wake
cycle and also responses to external stimuli including light and food. Initially
thought to be mainly involved in the timing of sleep, the clock, and/or clock
genes may also play a role in sleep architecture and homeostasis. Importantly, an
extensive body of evidence has firmly established a master regulatory role of the
clock in energy balance. Together, a close relationship between well-timed
circadian/sleep cycles and metabolic health is emerging. Exploiting this
functional connection, an important holistic strategy toward curbing the epidemic
of metabolic disorders (e.g., obesity) involves corrective measures on the
circadian clock and sleep. In addition to behavioral and environmental
interventions including meal timing and light control, pharmacological agents
targeting sleep and circadian clocks promise convenient and effective
applications. Recent studies, for example, have reported small molecules
targeting specific clock components and displaying robust beneficial effects on
sleep and metabolism. Furthermore, a group of clock-amplitude-enhancing small
molecules (CEMs) identified via high-throughput chemical screens are of
particular interest for future in vivo studies of their metabolic and sleep
efficacies. Elucidating the functional relationship between clock, sleep, and
metabolism will also have far-reaching implications for various chronic human
diseases and aging.
PMID- 25852647
TI - Micro CT Analysis of Spine Architecture in a Mouse Model of Scoliosis.
AB - OBJECTIVE: Mice homozygous for targeted deletion of the gene encoding fibroblast
growth factor receptor 3 (FGFR3(-/-)) develop kyphoscoliosis by 2 months of age.
The first objective of this study was to use high resolution X-ray to
characterize curve progression in vivo and micro CT to quantify spine
architecture ex vivo in FGFR3(-/-) mice. The second objective was to determine if
slow release of the bone anabolic peptide parathyroid hormone related protein
(PTHrP-1-34) from a pellet placed adjacent to the thoracic spine could inhibit
progressive kyphoscoliosis. MATERIALS AND METHODS: Pellets loaded with placebo or
PTHrP-1-34 were implanted adjacent to the thoracic spine of 1-month-old FGFR3(-/
) mice obtained from in house breeding. X rays were captured at monthly intervals
up to 4 months to quantify curve progression using the Cobb method. High
resolution post-mortem scans of FGFR3(-/-) and FGFR3(+/+) spines, from C5/6 to
L4/5, were captured to evaluate the 3D structure, rotation, and micro
architecture of the affected vertebrae. Un-decalcified and decalcified histology
were performed on the apical and adjacent vertebrae of FGFR3(-/-) spines, and the
corresponding vertebrae from FGFR3(+/+) spines. RESULTS: The mean Cobb angle was
significantly greater at all ages in FGFR3(-/-) mice compared with wild type mice
and appeared to stabilize around skeletal maturity at 4 months. 3D
reconstructions of the thoracic spine of 4-month-old FGFR3(-/-) mice treated with
PTHrP-1-34 revealed correction of left/right asymmetry, vertebral rotation, and
lateral displacement compared with mice treated with placebo. Histologic analysis
of the apical vertebrae confirmed correction of the asymmetry in PTHrP-1-34
treated mice, in the absence of any change in bone volume, and a significant
reduction in the wedging of intervertebral disks (IVD) seen in placebo treated
mice. CONCLUSION: Local treatment of the thoracic spine of juvenile FGFR3(-/-)
mice with a bone anabolic agent inhibited progression of scoliosis, but with
little impact on kyphosis. The significant improvement in IVD integrity suggests
PTHrP-1-34 might also be considered as a therapeutic agent for degenerative disk
disorders.
PMID- 25852648
TI - The Hypoxia-Inducible Factor Pathway in Adipocytes: The Role of HIF-2 in Adipose
Inflammation and Hypertrophic Cardiomyopathy.
AB - Under obese conditions, adipose tissue can become oxygen-deficient or hypoxic.
Extensive work has been done using various diet-induced obesity models to
demonstrate an important role of hypoxia-induced signaling in adipose tissue and
its impact on adipose functions related to adipogenesis, insulin sensitivity, and
inflammation. We have recently identified a new mechanism connecting activation
of the hypoxia-sensing pathway manifested by hypoxia-inducible factor (HIF)
2alpha to adipose tissue inflammation and hypertrophic cardiomyopathy.
Interestingly, this observation is consistent with the clinical evidence showing
that obesity is often associated with ventricular hypertrophy and dysfunction as
well as congestive heart failure independent of other well-established risk
factors including diabetes, hypertension, and coronary artery disease. This brief
review will discuss the currently published genetic mouse models to determine the
role of the HIF pathway in adipose tissue-associated diseases with a focus on the
newly identified role of adipocyte HIF-2 in the development of hypertrophic
cardiomyopathy.
PMID- 25852650
TI - Transcriptome analyses to investigate symbiotic relationships between marine
protists.
AB - Rhizaria are an important component of oceanic plankton communities worldwide. A
number of species harbor eukaryotic microalgal symbionts, which are horizontally
acquired in the environment at each generation. Although these photosymbioses are
determinant for Rhizaria ability to thrive in oceanic ecosystems, the mechanisms
for symbiotic interactions are unclear. Using high-throughput sequencing
technology (i.e., 454), we generated large Expressed Sequence Tag (EST) datasets
from four uncultured Rhizaria, an acantharian (Amphilonche elongata), two
polycystines (Collozoum sp. and Spongosphaera streptacantha), and one phaeodarian
(Aulacantha scolymantha). We assessed the main genetic features of the
host/symbionts consortium (i.e., the holobiont) transcriptomes and found rRNA
sequences affiliated to a wide range of bacteria and protists in all samples,
suggesting that diverse microbial communities are associated with the holobionts.
A particular focus was then carried out to search for genes potentially involved
in symbiotic processes such as the presence of c-type lectins-coding genes, which
are proteins that play a role in cell recognition among eukaryotes. Unigenes
coding putative c-type lectin domains (CTLD) were found in the species bearing
photosynthetic symbionts (A. elongata, Collozoum sp., and S. streptacantha) but
not in the non-symbiotic one (A. scolymantha). More particularly, phylogenetic
analyses group CTLDs from A. elongata and Collozoum sp. on a distinct branch from
S. streptacantha CTLDs, which contained carbohydrate-binding motifs typically
observed in other marine photosymbiosis. Our data suggest that similarly to other
well-known marine photosymbiosis involving metazoans, the interactions of glycans
with c-type lectins is likely involved in modulation of the host/symbiont
specific recognition in Radiolaria.
PMID- 25852649
TI - Coupling Signals between the Osteoclast and Osteoblast: How are Messages
Transmitted between These Temporary Visitors to the Bone Surface?
PMID- 25852651
TI - Endocytotic uptake of FITC-labeled anti-H. pylori egg yolk immunoglobulin Y in
Candida yeast for detection of intracellular H. pylori.
AB - Intracellular life of Helicobacter pylori inside Candida yeast vacuole describes
the establishment of H. pylori in yeast as a pre-adaptation to life in human
epithelial cells. IgY-Hp conjugated with fluorescein isothiocyanate (FITC) has
been previously used for identification and localization of H. pylori inside the
yeast vacuole. Here we examined whether FITC-IgY-Hp internalization into yeast
follows the endocytosis pathway in yeast. Fluorescent microscopy was used to
examine the entry of FITC-IgY-Hp into Candida yeast cells at different time
intervals. The effect of low temperature, H2O2 or acetic acid on the
internalization of labeled antibody was also examined. FITC-IgY-Hp
internalization initiated within 0-5 min in 5-10% of yeast cells, increased to 20
40% after 30 min-1 h and reached >70% before 2 h. FITC-IgY-Hp traversed the pores
of Candida yeast cell wall and reached the vacuole where it bound with H. pylori
antigens. Internalization of FITC-IgY-Hp was inhibited by low temperature, H2O2
or acetic acid. It was concluded that internalization of FITC-IgY-Hp into yeast
cell is a vital phenomenon and follows the endocytosis pathway. Furthermore, it
was proposed that FITC-IgY-Hp internalization could be recruited for localization
and identification of H. pylori inside the vacuole of Candida yeast.
PMID- 25852653
TI - Identification of a Novel Small Non-Coding RNA Modulating the Intracellular
Survival of Brucella melitensis.
AB - Bacterial small non-coding RNAs (sRNAs) are gene expression modulators respond to
environmental changes, stressful conditions, and pathogenesis. In this study, by
using a combined bioinformatic and experimental approach, eight novel sRNA genes
were identified in intracellular pathogen Brucella melitensis. BSR0602, one sRNA
that was highly induced in stationary phase, was further examined and found to
modulate the intracellular survival of B. melitensis. BSR0602 was present at very
high levels in vitro under stresses similar to those encountered during infection
in host macrophages. Furthermore, BSR0602 was found to be highly expressed in the
spleens of infected mice, suggesting its potential role in the control of
pathogenesis. BSR0602 targets the mRNAs coding for gntR, a global transcriptional
regulator, which is required for B. melitensis virulence. Overexpression of
BSR0602 results in distinct reduction in the gntR mRNA level. B. melitensis with
high level of BSR0602 is defective in bacteria intracellular survival in
macrophages and defective in growth in the spleens of infected mice. Therefore,
BSR0602 may directly inhibit the expression of gntR, which then impairs Brucellae
intracellular survival and contributes to Brucella infection. Our findings
suggest that BSR0602 is responsible for bacterial adaptation to stress conditions
and thus modulate B. melitensis intracellular survival.
PMID- 25852652
TI - The genus Weissella: taxonomy, ecology and biotechnological potential.
AB - Bacteria assigned to the genus Weissella are Gram-positive, catalase-negative,
non-endospore forming cells with coccoid or rod-shaped morphology (Collins et
al., 1993; Bjorkroth et al., 2009, 2014) and belong to the group of bacteria
generally known as lactic acid bacteria. Phylogenetically, the Weissella belong
to the Firmicutes, class Bacilli, order Lactobacillales and family
Leuconostocaceae (Collins et al., 1993). They are obligately heterofermentative,
producing CO2 from carbohydrate metabolism with either d(-)-, or a mixture of d(
)- and l(+)- lactic acid and acetic acid as major end products from sugar
metabolism. To date, there are 19 validly described Weissella species known.
Weissella spp. have been isolated from and occur in a wide range of habitats,
e.g., on the skin and in the milk and feces of animals, from saliva, breast milk,
feces and vagina of humans, from plants and vegetables, as well as from a variety
of fermented foods such as European sourdoughs and Asian and African traditional
fermented foods. Thus, apart from a perceived technical role of certain Weissella
species involved in such traditional fermentations, specific Weissella strains
are also receiving attention as potential probiotics, and strain development of
particularly W. cibaria strains is receiving attention because of their high
probiotic potential for controlling periodontal disease. Moreover, W. confusa and
W. cibaria strains are known to produce copius amounts of novel, non-digestible
oligosaccharides and extracellular polysaccharides, mainly dextran. These
polymers are receiving increased attention for their potential application as
prebiotics and for a wide range of industrial applications, predominantly for
bakeries and for the production of cereal-based fermented functional beverages.
On the detrimental side, strains of certain Weissella species, e.g., of W.
viridescens, W. cibaria and W. confusa, are known as opportunistic pathogens
involved in human infections while strains of W. ceti have been recently
recongnized as etiological agent of "weissellosis," which is a disease affecting
farmed rainbow trouts. Bacteria belonging to this species thus are important both
from a technological, as well as from a medical point of view, and both aspects
should be taken into account in any envisaged biotechnological applications.
PMID- 25852654
TI - A new high-performance heterologous fungal expression system based on regulatory
elements from the Aspergillus terreus terrein gene cluster.
AB - Recently, the Aspergillus terreus terrein gene cluster was identified and
selected for development of a new heterologous expression system. The cluster
encodes the specific transcription factor TerR that is indispensable for terrein
cluster induction. To identify TerR binding sites, different recombinant versions
of the TerR DNA-binding domain were analyzed for specific motif recognition. The
high affinity consensus motif TCGGHHWYHCGGH was identified from genes required
for terrein production and binding site mutations confirmed their essential
contribution to gene expression in A. terreus. A combination of TerR with its
terA target promoter was tested as recombinant expression system in the
heterologous host Aspergillus niger. TerR mediated target promoter activation was
directly dependent on its transcription level. Therefore, terR was expressed
under control of the regulatable amylase promoter PamyB and the resulting
activation of the terA target promoter was compared with activation levels
obtained from direct expression of reporters from the strong gpdA control
promoter. Here, the coupled system outcompeted the direct expression system. When
the coupled system was used for heterologous polyketide synthase expression high
metabolite levels were produced. Additionally, expression of the Aspergillus
nidulans polyketide synthase gene orsA revealed lecanoric acid rather than
orsellinic acid as major polyketide synthase product. Domain swapping experiments
assigned this depside formation from orsellinic acid to the OrsA thioesterase
domain. These experiments confirm the suitability of the expression system
especially for high-level metabolite production in heterologous hosts.
PMID- 25852655
TI - RNA shotgun metagenomic sequencing of northern California (USA) mosquitoes
uncovers viruses, bacteria, and fungi.
AB - Mosquitoes, most often recognized for the microbial agents of disease they may
carry, harbor diverse microbial communities that include viruses, bacteria, and
fungi, collectively called the microbiota. The composition of the microbiota can
directly and indirectly affect disease transmission through microbial
interactions that could be revealed by its characterization in natural
populations of mosquitoes. Furthermore, the use of shotgun metagenomic sequencing
(SMS) approaches could allow the discovery of unknown members of the microbiota.
In this study, we use RNA SMS to characterize the microbiota of seven individual
mosquitoes (species include Culex pipiens, Culiseta incidens, and Ochlerotatus
sierrensis) collected from a variety of habitats in California, USA. Sequencing
was performed on the Illumina HiSeq platform and the resulting sequences were
quality-checked and assembled into contigs using the A5 pipeline. Sequences
related to single stranded RNA viruses of the Bunyaviridae and Rhabdoviridae were
uncovered, along with an unclassified genus of double-stranded RNA viruses.
Phylogenetic analysis finds that in all three cases, the closest relatives of the
identified viral sequences are other mosquito-associated viruses, suggesting
widespread host-group specificity among disparate viral taxa. Interestingly, we
identified a Narnavirus of fungi, also reported elsewhere in mosquitoes, that
potentially demonstrates a nested host-parasite association between virus, fungi,
and mosquito. Sequences related to 8 bacterial families and 13 fungal families
were found across the seven samples. Bacillus and Escherichia/Shigella were
identified in all samples and Wolbachia was identified in all Cx. pipiens
samples, while no single fungal genus was found in more than two samples. This
study exemplifies the utility of RNA SMS in the characterization of the natural
microbiota of mosquitoes and, in particular, the value of identifying all
microbes associated with a specific host.
PMID- 25852658
TI - Stable microbial community composition on the Greenland Ice Sheet.
AB - The first molecular-based studies of microbes in snow and on glaciers have only
recently been performed on the vast Greenland Ice Sheet (GrIS). Aeolian microbial
seeding is hypothesized to impact on glacier surface community compositions.
Localized melting of glacier debris (cryoconite) into the surface ice forms
cryoconite holes, which are considered 'hot spots' for microbial activity on
glaciers. To date, few studies have attempted to assess the origin and evolution
of cryoconite and cryoconite hole communities throughout a melt season. In this
study, a range of experimental approaches was used for the first time to study
the inputs, temporal and structural transformations of GrIS microbial communities
over the course of a whole ablation season. Small amounts of aeolian (wind and
snow) microbes were potentially seeding the stable communities that were already
present on the glacier (composed mainly of Proteobacteria, Cyanobacteria, and
Actinobacteria). However, the dominant bacterial taxa in the aeolian samples
(Firmicutes) did not establish themselves in local glacier surface communities.
Cryoconite and cryoconite hole community composition remained stable throughout
the ablation season following the fast community turnover, which accompanied the
initial snow melt. The presence of stable communities in cryoconite and
cryoconite holes on the GrIS will allow future studies to assess glacier surface
microbial diversity at individual study sites from sampling intervals of short
duration only. Aeolian inputs also had significantly different organic delta(13)C
values (-28.0 to -27.00/00) from the glacier surface values (-25.7 to -23.60/00),
indicating that in situ microbial processes are important in fixing new organic
matter and transforming aeolian organic carbon. The continuous productivity of
stable communities over one melt season makes them important contributors to
biogeochemical nutrient cycling on glaciers.
PMID- 25852657
TI - Archaeal type IV pili and their involvement in biofilm formation.
AB - Type IV pili are ancient proteinaceous structures present on the cell surface of
species in nearly all bacterial and archaeal phyla. These filaments, which are
required for a diverse array of important cellular processes, are assembled
employing a conserved set of core components. While type IV pilins, the
structural subunits of pili, share little sequence homology, their signal
peptides are structurally conserved allowing for in silico prediction. Recently,
in vivo studies in model archaea representing the euryarchaeal and crenarchaeal
kingdoms confirmed that several of these pilins are incorporated into type IV
adhesion pili. In addition to facilitating surface adhesion, these in vivo
studies also showed that several predicted pilins are required for additional
functions that are critical to biofilm formation. Examples include the subunits
of Sulfolobus acidocaldarius Ups pili, which are induced by exposure to UV light
and promote cell aggregation and conjugation, and a subset of the Haloferax
volcanii adhesion pilins, which play a critical role in microcolony formation
while other pilins inhibit this process. The recent discovery of novel pilin
functions such as the ability of haloarchaeal adhesion pilins to regulate
swimming motility may point to novel regulatory pathways conserved across
prokaryotic domains. In this review, we will discuss recent advances in our
understanding of the functional roles played by archaeal type IV adhesion pili
and their subunits, with particular emphasis on their involvement in biofilm
formation.
PMID- 25852656
TI - Redox regulation by reversible protein S-thiolation in bacteria.
AB - Low molecular weight (LMW) thiols function as thiol-redox buffers to maintain the
reduced state of the cytoplasm. The best studied LMW thiol is the tripeptide
glutathione (GSH) present in all eukaryotes and Gram-negative bacteria.
Firmicutes bacteria, including Bacillus and Staphylococcus species utilize the
redox buffer bacillithiol (BSH) while Actinomycetes produce the related redox
buffer mycothiol (MSH). In eukaryotes, proteins are post-translationally modified
to S-glutathionylated proteins under conditions of oxidative stress. S
glutathionylation has emerged as major redox-regulatory mechanism in eukaryotes
and protects active site cysteine residues against overoxidation to sulfonic
acids. First studies identified S-glutathionylated proteins also in Gram-negative
bacteria. Advances in mass spectrometry have further facilitated the
identification of protein S-bacillithiolations and S-mycothiolation as BSH- and
MSH-mixed protein disulfides formed under oxidative stress in Firmicutes and
Actinomycetes, respectively. In Bacillus subtilis, protein S-bacillithiolation
controls the activities of the redox-sensing OhrR repressor and the methionine
synthase MetE in vivo. In Corynebacterium glutamicum, protein S-mycothiolation
was more widespread and affected the functions of the maltodextrin phosphorylase
MalP and thiol peroxidase (Tpx). In addition, novel bacilliredoxins (Brx) and
mycoredoxins (Mrx1) were shown to function similar to glutaredoxins in the
reduction of BSH- and MSH-mixed protein disulfides. Here we review the current
knowledge about the functions of the bacterial thiol-redox buffers glutathione,
bacillithiol, and mycothiol and the role of protein S-thiolation in redox
regulation and thiol protection in model and pathogenic bacteria.
PMID- 25852659
TI - Green materials science and engineering reduces biofouling: approaches for
medical and membrane-based technologies.
AB - Numerous engineered and natural environments suffer deleterious effects from
biofouling and/or biofilm formation. For instance, bacterial contamination on
biomedical devices pose serious health concerns. In membrane-based technologies,
such as desalination and wastewater reuse, biofouling decreases membrane
lifetime, and increases the energy required to produce clean water.
Traditionally, approaches have combatted bacteria using bactericidal agents.
However, due to globalization, a decline in antibiotic discovery, and the
widespread resistance of microbes to many commercial antibiotics and metallic
nanoparticles, new materials, and approaches to reduce biofilm formation are
needed. In this mini-review, we cover the recent strategies that have been
explored to combat microbial contamination without exerting evolutionary pressure
on microorganisms. Renewable feedstocks, relying on structure-property
relationships, bioinspired/nature-derived compounds, and green processing methods
are discussed. Greener strategies that mitigate biofouling hold great potential
to positively impact human health and safety.
PMID- 25852660
TI - The transcriptional response of microbial communities in thawing Alaskan
permafrost soils.
AB - Thawing of permafrost soils is expected to stimulate microbial decomposition and
respiration of sequestered carbon. This could, in turn, increase atmospheric
concentrations of greenhouse gasses, such as carbon dioxide and methane, and
create a positive feedback to climate warming. Recent metagenomic studies suggest
that permafrost has a large metabolic potential for carbon processing, including
pathways for fermentation and methanogenesis. Here, we performed a pilot study
using ultrahigh throughput Illumina HiSeq sequencing of reverse transcribed
messenger RNA to obtain a detailed overview of active metabolic pathways and
responsible organisms in up to 70 cm deep permafrost soils at a moist acidic
tundra location in Arctic Alaska. The transcriptional response of the permafrost
microbial community was compared before and after 11 days of thaw. In general,
the transcriptional profile under frozen conditions suggests a dominance of
stress responses, survival strategies, and maintenance processes, whereas upon
thaw a rapid enzymatic response to decomposing soil organic matter (SOM) was
observed. Bacteroidetes, Firmicutes, ascomycete fungi, and methanogens were
responsible for largest transcriptional response upon thaw. Transcripts
indicative of heterotrophic methanogenic pathways utilizing acetate, methanol,
and methylamine were found predominantly in the permafrost table after thaw.
Furthermore, transcripts involved in acetogenesis were expressed exclusively
after thaw suggesting that acetogenic bacteria are a potential source of acetate
for acetoclastic methanogenesis in freshly thawed permafrost. Metatranscriptomics
is shown here to be a useful approach for inferring the activity of permafrost
microbes that has potential to improve our understanding of permafrost SOM
bioavailability and biogeochemical mechanisms contributing to greenhouse gas
emissions as a result of permafrost thaw.
PMID- 25852661
TI - Isolation and characterization of plant growth-promoting rhizobacteria from wheat
rhizosphere and their effect on plant growth promotion.
AB - The present study was conducted to characterize the native plant growth promoting
(PGP) bacteria from wheat rhizosphere and root-endosphere in the Himalayan region
of Rawalakot, Azad Jammu and Kashmir (AJK), Pakistan. Nine bacterial isolates
were purified, screened in vitro for PGP characteristics and evaluated for their
beneficial effects on the early growth of wheat (Triticum aestivum L.). Among
nine bacterial isolates, seven were able to produce indole-3- acetic acid in
tryptophan-supplemented medium; seven were nitrogen fixer, and four were able to
solubilize inorganic phosphate in vitro. Four different morphotypes were
genotypically identified based on IGS-RFLP fingerprinting and representative of
each morphotype was identified by 16S rRNA gene sequencing analysis except Gram
positive putative Bacillus sp. Based on 16S rRNA gene sequence analysis,
bacterial isolates AJK-3 and AJK-9 showing multiple PGP-traits were identified as
Stenotrophomonas spp. while AJK-7 showed equal homologies to Acetobacter
pasteurianus and Stenotrophomonas specie. Plant inoculation studies indicated
that these Plant growth-promoting rhizobacteria (PGPR) strains provided a
significant increase in shoot and root length, and shoot and root biomass. A
significant increase in shoot N contents (up to 76%) and root N contents (up to
32%) was observed over the un-inoculated control. The study indicates the
potential of these PGPR for inoculums production or biofertilizers for enhancing
growth and nutrient content of wheat and other crops under field conditions. The
study is the first report of wheat associated bacterial diversity in the
Himalayan region of Rawalakot, AJK.
PMID- 25852663
TI - Microbial methane formation in deep aquifers of a coal-bearing sedimentary basin,
Germany.
AB - Coal-bearing sediments are major reservoirs of organic matter potentially
available for methanogenic subsurface microbial communities. In this study the
specific microbial community inside lignite-bearing sedimentary basin in Germany
and its contribution to methanogenic hydrocarbon degradation processes was
investigated. The stable isotope signature of methane measured in groundwater and
coal-rich sediment samples indicated methanogenic activity. Analysis of 16S rRNA
gene sequences showed the presence of methanogenic Archaea, predominantly
belonging to the orders Methanosarcinales and Methanomicrobiales, capable of
acetoclastic or hydrogenotrophic methanogenesis. Furthermore, we identified
fermenting, sulfate-, nitrate-, and metal-reducing, or acetogenic Bacteria
clustering within the phyla Proteobacteria, complemented by members of the
classes Actinobacteria, and Clostridia. The indigenous microbial communities
found in the groundwater as well as in the coal-rich sediments are able to
degrade coal-derived organic components and to produce methane as the final
product. Lignite-bearing sediments may be an important nutrient and energy source
influencing larger compartments via groundwater transport.
PMID- 25852664
TI - Disruption of mycorrhizal extraradical mycelium and changes in leaf water status
and soil aggregate stability in rootbox-grown trifoliate orange.
AB - Arbuscular mycorrhizas possess well developed extraradical mycelium (ERM) network
that enlarge the surrounding soil for better acquisition of water and nutrients,
besides soil aggregation. Distinction in ERM functioning was studied under a
rootbox system, which consisted of root+hyphae and root-free hyphae compartments
separated by 37-MUm nylon mesh with an air gap. Trifoliate orange (Poncirus
trifoliata) seedlings were inoculated with Funneliformis mosseae in root+hyphae
compartment, and the ERM network was established between the two compartments.
The ERM network of air gap was disrupted before 8 h of the harvest (one time
disruption) or multiple disruptions during seedlings acclimation. Our results
showed that mycorrhizal inoculation induced a significant increase in growth
(plant height, stem diameter, and leaf, stem, and root biomass) and physiological
characters (leaf relative water content, leaf water potential, and transpiration
rate), irrespective of ERM status. Easily-extractable glomalin-related soil
protein (EE-GRSP) and total GRSP (T-GRSP) concentration and mean weight diameter
(MWD, an indicator of soil aggregate stability) were significantly higher in
mycorrhizosphere of root+hyphae and root-free hyphae compartments than non
mycorrhizosphere. One time disruption of ERM network did not influence plant
growth and soil properties but only notably decreased leaf water. Periodical
disruption of ERM network at weekly interval markedly inhibited the mycorrhizal
roles on plant growth, leaf water, GRSP production, and MWD in root+hyphae and
hyphae chambers. EE-GRSP was the most responsive GRSP fraction to changes in leaf
water and MWD under root+hyphae and hyphae conditions. It suggests that effect of
peridical disruption of ERM network was more impactful than one-time disruption
of ERM network with regard to leaf water, plant growth, and aggregate stability
responses, thereby, implying ERM network aided in developing the host plant
metabolically more active.
PMID- 25852662
TI - Genomic characteristics and environmental distributions of the uncultivated Far
T4 phages.
AB - Viral metagenomics (viromics) is a tremendous tool to reveal viral taxonomic and
functional diversity across ecosystems ranging from the human gut to the world's
oceans. As with microbes however, there appear vast swaths of "dark matter" yet
to be documented for viruses, even among relatively well-studied viral types.
Here, we use viromics to explore the "Far-T4 phages" sequence space, a neighbor
clade from the well-studied T4-like phages that was first detected through PCR
study in seawater and subsequently identified in freshwater lakes through 454
sequenced viromes. To advance the description of these viruses beyond this single
marker gene, we explore Far-T4 genome fragments assembled from two deeply
sequenced freshwater viromes. Single gene phylogenetic trees confirm that the Far
T4 phages are divergent from the T4-like phages, genome fragments reveal largely
collinear genome organizations, and both data led to the delineation of five Far
T4 clades. Three-dimensional models of major capsid proteins are consistent with
a T4-like structure, and highlight a highly conserved core flanked by variable
insertions. Finally, we contextualize these now better characterized Far-T4
phages by re-analyzing 196 previously published viromes. These suggest that Far
T4 are common in freshwater and seawater as only four of 82 aquatic viromes
lacked Far-T4-like sequences. Variability in representation across the five newly
identified clades suggests clade-specific niche differentiation may be occurring
across the different biomes, though the underlying mechanism remains
unidentified. While complete genome assembly from complex communities and the
lack of host linkage information still bottleneck virus discovery through
viromes, these findings exemplify the power of metagenomics approaches to assess
the diversity, evolutionary history, and genomic characteristics of novel
uncultivated phages.
PMID- 25852665
TI - Insights into the environmental reservoir of pathogenic Vibrio parahaemolyticus
using comparative genomics.
AB - Vibrio parahaemolyticus is an aquatic halophilic bacterium that occupies
estuarine and coastal marine environments, and is a leading cause of seafood
borne food poisoning cases. To investigate the environmental reservoir and
potential gene flow that occurs among V. parahaemolyticus isolates, the virulence
associated gene content and genome diversity of a collection of 133 V.
parahaemolyticus isolates were analyzed. Phylogenetic analysis of housekeeping
genes, and pulsed-field gel electrophoresis, demonstrated that there is genetic
similarity among V. parahaemolyticus clinical and environmental isolates. Whole
genome sequencing and comparative analysis of six representative V.
parahaemolyticus isolates was used to identify genes that are unique to the
clinical and environmental isolates examined. Comparative genomics demonstrated
an O3:K6 environmental isolate, AF91, which was cultured from sediment collected
in Florida in 2006, has significant genomic similarity to the post-1995 O3:K6
isolates. However, AF91 lacks the majority of the virulence-associated genes and
genomic islands associated with these highly virulent post-1995 O3:K6 genomes.
These findings demonstrate that although they do not contain most of the known
virulence-associated regions, some V. parahaemolyticus environmental isolates
exhibit significant genetic similarity to clinical isolates. This highlights the
dynamic nature of the V. parahaemolyticus genome allowing them to transition
between aquatic and host-pathogen states.
PMID- 25852666
TI - Silver linings: a personal memoir about Hurricane Katrina and fungal volatiles.
AB - In the aftermath of Hurricane Katrina, the levees protecting New Orleans,
Louisiana failed. Because approximately 80% of the city was under sea level,
widespread flooding ensued. As a resident of New Orleans who had evacuated before
the storm and a life-long researcher on filamentous fungi, I had known what to
expect. After the hurricane I traveled home with a suitcase full of Petri dishes
and sampling equipment so as to study the fungi that were "eating my house." Not
only were surfaces covered with fungal growth, the air itself was full of
concentrated mold odor, a smell that was orders of magnitude more funky than any
damp, musty basement I had ever encountered. The smell made me feel bad and I had
to take regular breaks as I sampled. Being a mycotoxin expert, I knew a fair
amount about "sick building syndrome" but believed that it was difficult to get
enough respiratory exposure to toxins to cause the array of symptoms associated
with the syndrome. So why was I feeling sick? Some Scandinavian experts had
hypothesized that mold volatile organic compounds (VOCs) might be the fungal
metabolites to blame for sick building syndrome and the time in my smelly, mold
infested home made me think they might be right. After securing a new job and
establishing a new laboratory, I endeavored to test the hypothesis that some
volatile mold metabolites might be toxic. My laboratory at Rutgers University has
interrogated the role of VOCs in possible interkingdom toxicity by developing
controlled microcosms for exposing simple genetic model organisms to the vapor
phase of growing fungi. Both Arabidopsis thaliana and Drosophila melanogaster
exhibit a range of toxic symptoms that vary with the species of fungus, the
duration of exposure, and other experimental parameters. Moreover, low
concentrations of chemical standards of individual fungal VOCs such as 1-octen-3
ol also exhibit varying toxicity and cause neurotoxicity in a Drosophila model.
Collectively, these data suggest that fungal VOCs may contribute to some of the
adverse health effects reported by people exposed to damp indoor environments and
that biogenic gas phase molecules deserve increased attention by the research
community.
PMID- 25852667
TI - Isolation and identification of indigenous plant growth promoting rhizobacteria
from Himalayan region of Kashmir and their effect on improving growth and
nutrient contents of maize (Zea mays L.).
AB - Introduction and exploitation of plant growth promoting rhizobacteria (PGPR) in
agro-ecosystems enhance plant-microbes interactions that may affect ecosystems
sustainability, agricultural productivity, and environmental quality. The present
study was conducted to isolate and identify PGPRs associated with maize (Zea mays
L.) from twenty sites of Himalayan region of Hajira-Rawalakot, Azad Jammu and
Kashmir (AJK), Pakistan. A total of 100 isolates were isolated from these sites,
out of which eight (HJR1, HJR2, HJR3, HJR4, HJR5, MR6, HJR7, HJR8) were selected
in vitro for their plant growth promoting ability (PGPA) including phosphorus
solubilization, indole-3-acetic acid (IAA) production and N2 fixation. The 16S
rRNA gene sequencing technique was used for molecular identity and
authentication. Isolates were then further tested for their effects on growth and
nutrient contents of maize (Z. mays L.) under pouch and pot conditions. The 16S
rRNA gene sequencing and phylogenetic analysis identified these isolates belong
to Pseudomonas and Bacillus genera. The isolates promoted plant growth by
solubilizing soil P which ranged between 19.2 and 35.6 MUg mL(-1). The isolates
HJR1, HJR2, HJR3, and HJR5 showed positive activity in acetylene reduction assay
showing their N2-fixation potential. All eight isolates showed the potential to
produce IAA in the range of 0.9-5.39 MUg mL(-1) and promote plant growth. Results
from a subsequent pot experiment indicated PGPRs distinctly increased maize shoot
and root length, shoot and root dry weight, root surface area, leaf surface area,
shoot and root N and P contents. Among the eight isolates, HR3 showed a marked P
solubilizing activity, plant growth-promoting attributes, and the potential to be
developed as a biofertilizers for integrated nutrient management strategies.
PMID- 25852669
TI - Development of a bacterial bioassay for atrazine and cyanuric acid detection.
AB - The s-triazine herbicides are compounds which can disseminate into soils and
water. Due to their toxic effects on living organisms, their concentrations in
drinking water are legislated by WHO recommendations. Here we have developed for
the first time, to the best of our knowledge, an alternative method for
physicochemical quantification using two bioluminescent bacterial biosensors: E.
coli SM003 for cyanuric acid detection and E. coli SM004 for both atrazine and
cyanuric acid detection. The concentration of cyanuric acid detection for E. coli
SM003 ranges from 7.83 MUM to 2.89 mM, and for E. coli SM004 ranges from 0.22 to
15 MUM. Moreover, atrazine detection by E. coli SM004 ranges from 1.08 to 15 MUM.
According to WHO recommendations, the cyanuric acid detection range is sensitive
enough to discriminate between polluted and drinking water. Nevertheless, the
detection of atrazine by E. coli SM004 is only applicable for high concentrations
of contaminants.
PMID- 25852668
TI - Influence of Martian regolith analogs on the activity and growth of methanogenic
archaea, with special regard to long-term desiccation.
AB - Methanogenic archaea have been studied as model organisms for possible life on
Mars for several reasons: they can grow lithoautotrophically by using hydrogen
and carbon dioxide as energy and carbon sources, respectively; they are
anaerobes; and they evolved at a time when conditions on early Earth are believed
to have looked similar to those of early Mars. As Mars is currently dry and cold
and as water might be available only at certain time intervals, any organism
living on this planet would need to cope with desiccation. On Earth there are
several regions with low water availability as well, e.g., permafrost
environments, desert soils, and salt pans. Here, we present the results of a set
of experiments investigating the influence of different Martian regolith analogs
(MRAs) on the metabolic activity and growth of three methanogenic strains exposed
to culture conditions as well as long-term desiccation. In most cases,
concentrations below 1 wt% of regolith in the media resulted in an increase of
methane production rates, whereas higher concentrations decreased the rates, thus
prolonging the lag phase. Further experiments showed that methanogenic archaea
are capable of producing methane when incubated on a water-saturated sedimentary
matrix of regolith lacking nutrients. Survival of methanogens under these
conditions was analyzed with a 400 day desiccation experiment in the presence of
regolith analogs. All tested strains of methanogens survived the desiccation
period as it was determined through reincubation on fresh medium and via qPCR
following propidium monoazide treatment to identify viable cells. The survival of
long-term desiccation and the ability of active metabolism on water-saturated
MRAs strengthens the possibility of methanogenic archaea or physiologically
similar organisms to exist in environmental niches on Mars. The best results were
achieved in presence of a phyllosilicate, which provides insights of possible
positive effects in habitats on Earth as well.
PMID- 25852672
TI - Commentary on: "Detection of Toxoplasma gondii in raw caprine, ovine, buffalo,
bovine, and camel milk using cell cultivation, cat bioassay, capture ELISA, and
PCR methods in Iran".
PMID- 25852671
TI - Systems modeling approaches for microbial community studies: from metagenomics to
inference of the community structure.
AB - Microbial communities play important roles in health, industrial applications and
earth's ecosystems. With current molecular techniques we can characterize these
systems in unprecedented detail. However, such methods provide little mechanistic
insight into how the genetic properties and the dynamic couplings between
individual microorganisms give rise to their dynamic activities. Neither do they
give insight into what we call "the community state", that is the fluxes and
concentrations of nutrients within the community. This knowledge is a
prerequisite for rational control and intervention in microbial communities.
Therefore, the inference of the community structure from experimental data is a
major current challenge. We will argue that this inference problem requires
mathematical models that can integrate heterogeneous experimental data with
existing knowledge. We propose that two types of models are needed. Firstly,
mathematical models that integrate existing genomic, physiological, and
physicochemical information with metagenomics data so as to maximize information
content and predictive power. This can be achieved with the use of constraint
based genome-scale stoichiometric modeling of community metabolism which is
ideally suited for this purpose. Next, we propose a simpler coarse-grained model,
which is tailored to solve the inference problem from the experimental data. This
model unambiguously relate to the more detailed genome-scale stoichiometric
models which act as heterogeneous data integrators. The simpler inference models
are, in our opinion, key to understanding microbial ecosystems, yet until now,
have received remarkably little attention. This has led to the situation where
the modeling of microbial communities, using only genome-scale models is
currently more a computational, theoretical exercise than a method useful to the
experimentalist.
PMID- 25852670
TI - Surfactants tailored by the class Actinobacteria.
AB - Globally the change towards the establishment of a bio-based economy has resulted
in an increased need for bio-based applications. This, in turn, has served as a
driving force for the discovery and application of novel biosurfactants. The
class Actinobacteria represents a vast group of microorganisms with the ability
to produce a diverse range of secondary metabolites, including surfactants.
Understanding the extensive nature of the biosurfactants produced by
actinobacterial strains can assist in finding novel biosurfactants with new
potential applications. This review therefore presents a comprehensive overview
of the knowledge available on actinobacterial surfactants, the chemical
structures that have been completely or partly elucidated, as well as the
identity of the biosurfactant-producing strains. Producer strains of not yet
elucidated compounds are discussed, as well as the original habitats of all the
producer strains, which seems to indicate that biosurfactant production is
environmentally driven. Methodology applied in the isolation, purification and
structural elucidation of the different types of surface active compounds, as
well as surfactant activity tests, are also discussed. Overall, actinobacterial
surfactants can be summarized to include the dominantly occurring trehalose
comprising surfactants, other non-trehalose containing glycolipids, lipopeptides
and the more rare actinobacterial surfactants. The lack of structural information
on a large proportion of actinobacterial surfactants should be considered as a
driving force to further explore the abundance and diversity of these compounds.
This would allow for a better understanding of actinobacterial surface active
compounds and their potential for biotechnological application.
PMID- 25852673
TI - Drugs of Abuse in HIV infection and neurotoxicity.
PMID- 25852674
TI - Beyond the iron age: the ecological relevance of non-ferrous bioactive trace
metals and organic growth factors in aquatic systems.
PMID- 25852676
TI - Effect of Puumala hantavirus infection on human umbilical vein endothelial cell
hemostatic function: platelet interactions, increased tissue factor expression
and fibrinolysis regulator release.
AB - Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in
Europe annually and can influence the hemostatic balance extensively. Infection
might lead to hemorrhage, while a recent study showed an increased risk of
myocardial infarction during or shortly after PUUV infection. The mechanism by
which this hantavirus influences the coagulation system remains unknown.
Therefore we aimed to elucidate mechanisms explaining alterations seen in primary
and secondary hemostasis during PUUV infection. By using low passage PUUV
isolates to infect primary human umbilical vein endothelial cells (HUVECs) we
were able to show alterations in the regulation of primary- and secondary
hemostasis and in the release of fibrinolysis regulators. Our main finding was an
activation of secondary hemostasis due to increased tissue factor (TF) expression
leading to increased thrombin generation in a functional assay. Furthermore, we
showed that during infection platelets adhered to HUVEC and subsequently
specifically to PUUV virus particles. Infection of HUVEC with PUUV did not result
in increased von Willebrand factor while they produced more plasminogen activator
inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model
formed complexes with vitronectin. This is the first report that reveals a
potential mechanism behind the pro-coagulant changes in PUUV patients, which
could be the result of increased thrombin generation due to an increased TF
expression on endothelial cells during infection. Furthermore, we provide insight
into the contribution of endothelial cell responses regarding hemostasis in PUUV
pathogenesis.
PMID- 25852675
TI - The composition of the global and feature specific cyanobacterial core-genomes.
AB - Cyanobacteria are photosynthetic prokaryotes important for many ecosystems with a
high potential for biotechnological usage e.g., in the production of bioactive
molecules. Either asks for a deep understanding of the functionality of
cyanobacteria and their interaction with the environment. This in part can be
inferred from the analysis of their genomes or proteomes. Today, many
cyanobacterial genomes have been sequenced and annotated. This information can be
used to identify biological pathways present in all cyanobacteria as proteins
involved in such processes are encoded by a so called core-genome. However,
beside identification of fundamental processes, genes specific for certain
cyanobacterial features can be identified by a holistic genome analysis as well.
We identified 559 genes that define the core-genome of 58 analyzed cyanobacteria,
as well as three genes likely to be signature genes for thermophilic and 57 genes
likely to be signature genes for heterocyst-forming cyanobacteria. To get
insights into cyanobacterial systems for the interaction with the environment we
also inspected the diversity of the outer membrane proteome with focus on beta
barrel proteins. We observed that most of the transporting outer membrane beta
barrel proteins are not globally conserved in the cyanobacterial phylum. In turn,
the occurrence of beta-barrel proteins shows high strain specificity. The core
set of outer membrane proteins globally conserved in cyanobacteria comprises
three proteins only, namely the outer membrane beta-barrel assembly protein
Omp85, the lipid A transfer protein LptD, and an OprB-type porin. Thus, we
conclude that cyanobacteria have developed individual strategies for the
interaction with the environment, while other intracellular processes like the
regulation of the protein homeostasis are globally conserved.
PMID- 25852677
TI - A pandemic Vibrio parahaemolyticus O3:K6 clone causing most associated diarrhea
cases in the Pacific Northwest coast of Mexico.
AB - Between September and October of 2004, more than 1230 cases of gastroenteritis
due to pandemic O3:K6 strains of Vibrio parahaemolyticus (V. parahaemolyticus)
were reported in the relatively small geographical area of Southern Sinaloa, a
state located in Northwest Mexico. Since then, V. parahaemolyticus-associated
gastroenteritis cases have gradually increased in prevalence spreading from south
to north. The present study conducted an epidemiological surveillance of V.
parahaemolyticus strains in both environmental and clinical samples along the
Pacific coast of Sinaloa from 2011 to 2013. The genetic relatedness, serotype
dominance and antibiotic resistance of isolates were investigated. A total of 46
strains were isolated from environmental samples (e.g., sediment, seawater and
shrimp), whereas 249 strains were obtained from stools of patients with
gastroenteritis. Nine different O serogroups and 16 serovars were identified.
Serovars O3:K6 and O6:K46 were identified in both environmental and clinical
strains. Whereas most environmental isolates carried the tdh gene (71.74%,
33/46), only three (6.52%) belonged to pandemic clones (O3:K6, O3:KUT and
OUT:KUT). In contrast, 81.1% (202/249) of clinical isolates belonged to pandemic
serotypes, with O3:K6 (tdh, toxRS/new, and/or orf8) representing the predominant
serovar (97%, 196/202). This prevalence of pathogenic (tdh and/or trh positive)
and O3:K6 pandemic V. parahaemolyticus isolates in this study were similar to
those found from 2004 to 2010. As investigated by REP-PCR, genetic lineages of
selected O3:K6 strains isolated in this study and some isolated earlier were
nearly identical. Antimicrobial susceptibility testing showed that most strains
(93.8%) were resistant to ampicillin but sensitive to chloramphenicol (98.8%).
Multidrug resistance significantly increased from 8.6% (2004-2010) to 22.93%
(2011-2013; p < 0.05). Our data indicate that pandemic O3:K6 clone has
endemically established in the Pacific Coast of Mexico.
PMID- 25852678
TI - Microbial abundance in surface ice on the Greenland Ice Sheet.
AB - Measuring microbial abundance in glacier ice and identifying its controls is
essential for a better understanding and quantification of biogeochemical
processes in glacial ecosystems. However, cell enumeration of glacier ice samples
is challenging due to typically low cell numbers and the presence of interfering
mineral particles. We quantified for the first time the abundance of microbial
cells in surface ice from geographically distinct sites on the Greenland Ice
Sheet (GrIS), using three enumeration methods: epifluorescence microscopy (EFM),
flow cytometry (FCM), and quantitative polymerase chain reaction (qPCR). In
addition, we reviewed published data on microbial abundance in glacier ice and
tested the three methods on artificial ice samples of realistic cell (10(2)-10(7)
cells ml(-1)) and mineral particle (0.1-100 mg ml(-1)) concentrations, simulating
a range of glacial ice types, from clean subsurface ice to surface ice to
sediment-laden basal ice. We then used multivariate statistical analysis to
identify factors responsible for the variation in microbial abundance on the ice
sheet. EFM gave the most accurate and reproducible results of the tested
methodologies, and was therefore selected as the most suitable technique for cell
enumeration of ice containing dust. Cell numbers in surface ice samples,
determined by EFM, ranged from ~ 2 * 10(3) to ~ 2 * 10(6) cells ml(-1) while dust
concentrations ranged from 0.01 to 2 mg ml(-1). The lowest abundances were found
in ice sampled from the accumulation area of the ice sheet and in samples
affected by fresh snow; these samples may be considered as a reference point of
the cell abundance of precipitants that are deposited on the ice sheet surface.
Dust content was the most significant variable to explain the variation in the
abundance data, which suggests a direct association between deposited dust
particles and cells and/or by their provision of limited nutrients to microbial
communities on the GrIS.
PMID- 25852679
TI - rpoN1, but not rpoN2, is required for twitching motility, natural competence,
growth on nitrate, and virulence of Ralstonia solanacearum.
AB - The plant pathogen Ralstonia solanacearum has two genes encoding for the sigma
factor sigma(54): rpoN1, located in the chromosome and rpoN2, located in a
distinct "megaplasmid" replicon. In this study, individual mutants as well as a
double mutant of rpoN were created in R. solanacearum strain GMI1000 in order to
determine the extent of functional overlap between these two genes. By virulence
assay we observed that rpoN1 is required for virulence whereas rpoN2 is not. In
addition rpoN1 controls other important functions such twitching motility,
natural transformation and growth on nitrate, unlike rpoN2. The rpoN1 and rpoN2
genes have different expression pattern, the expression of rpoN1 being
constitutive whereas rpoN2 expression is induced in minimal medium and in the
presence of plant cells. Moreover, the expression of rpoN2 is dependent upon
rpoN1. Our work therefore reveals that the two rpoN genes are not functionally
redundant in R. solanacearum. A list of potential sigma(54) targets was
identified in the R. solanacearum genome and suggests that multiple traits are
under the control of these regulators. Based on these findings, we provide a
model describing the functional connection between RpoN1 and the PehR
pathogenicity regulator and their dual role in the control of several R.
solanacearum virulence determinants.
PMID- 25852680
TI - Structural and molecular determinants of HIV-1 Gag binding to the plasma
membrane.
AB - Targeting of the Gag polyprotein to the plasma membrane (PM) for assembly is a
critical event in the late phase of immunodeficiency virus type-1 (HIV-1)
infection. Gag binding to the PM is mediated by interactions between the
myristoylated matrix (MA) domain and PM lipids. Despite the extensive biochemical
and in vitro studies of Gag and MA binding to membranes over the last two
decades, the discovery of the role of phosphatidylinositol-4,5-bisphosphate
[PI(4,5)P2] in Gag binding to the PM has sparked a string of studies aimed at
elucidating the molecular mechanism of retroviral Gag-PM binding. Electrostatic
interactions between a highly conserved basic region of MA and acidic
phospholipids have long been thought to be the main driving force for Gag
membrane interactions. However, recent studies suggest that the mechanism is
rather complex since other factors such as the hydrophobicity of the membrane
interior represented by the acyl chains and cholesterol also play important
roles. Here we summarize the current understanding of HIV-1 Gag-membrane
interactions at the molecular and structural levels and briefly discuss the
underlying forces governing interactions of other retroviral MA proteins with the
PM.
PMID- 25852681
TI - Environmental and metabolic sensors that control T cell biology.
AB - The T lymphocyte response to pathogens is shaped by the microenvironment.
Environmental sensors in T cells include the nutrient-sensing serine/threonine
kinases, adenosine monophosphate-activated protein kinase and mammalian target of
rapamycin complex 1. Other environmental sensors are transcription factors such
as hypoxia-inducible factor-1 and the aryl hydrocarbon receptor. The present
review explores the molecular basis for the impact of environmental signals on
the differentiation of conventional T cell receptor alphabeta T cells and how the
T cell response to immune stimuli can coordinate the T cell response to
environmental cues.
PMID- 25852684
TI - The genomic load of deleterious mutations: relevance to death in infancy and
childhood.
AB - The human diploid genome has approximately 40,000 functioning conserved genes
distributed within 6 billion base pairs of DNA. Most individuals carry a few
heterozygous deleterious mutations and this leads to an increased risk of
recessive disease in the offspring of cousin unions. Rare recessive disease is
more common in the children of cousin marriages than in the general population,
even though <1% of marriages in the Western World are between first cousins. But
more than 90% of the children of cousin marriages do not have recessive disease
and are as healthy as the rest of the population. A mathematical model based on
these observations generates simultaneous equations linking the mean number of
deleterious mutations in the genome of adults (M), the mean number of new
deleterious mutations arising in gametogenesis and passed to the next generation
(N) and the number of genes in the human diploid genome (L). The best estimates
are that M is <7 and N is approximately 1. The nature of meiosis indicates that
deleterious mutations in zygotes will have a Poisson distribution with a mean of
M + N. There must be strong selective pressure against zygotes at the upper end
of the Poisson distribution otherwise the value of M would rise with each
generation. It is suggested that this selection is based on synergistic
interaction of heterozygous deleterious mutations acting in large complex highly
redundant and robust genetic networks. To maintain the value of M in single
figures over many thousands of generations means that the zygote loss must be of
the order of 30%. Most of this loss will occur soon after conception but some
will occur later; during fetal development, in infancy and even in childhood.
Selection means genetic death and this is caused by disease to which the
deleterious mutations predispose. In view of this genome sequencing should be
undertaken in all infant deaths in which the cause of death is not ascertained by
standard techniques.
PMID- 25852683
TI - Innate immune activation by tissue injury and cell death in the setting of
hematopoietic stem cell transplantation.
AB - Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with donor
lymphocyte infusion is the mainstay of treatment for many types of hematological
malignancies, but the therapeutic effect and prevention of relapse is complicated
by donor T-cell recognition and attack of host tissue in a process known as graft
versus-host disease (GvHD). Cytotoxic myeloablative conditioning regimens used
prior to Allo-HSCT result in the release of endogenous innate immune activators
that are increasingly recognized for their role in creating a pro-inflammatory
milieu. This increased inflammatory state promotes allogeneic T-cell activation
and the induction and perpetuation of GvHD. Here, we review the processes of
cellular response to injury and cell death that are relevant following Allo-HSCT
and present the current evidence for a causative role of a variety of endogenous
innate immune activators in the mediation of sterile inflammation following Allo
HSCT. Finally, we discuss the potential therapeutic strategies that target the
endogenous pathways of innate immune activation to decrease the incidence and
severity of GvHD following Allo-HSCT.
PMID- 25852685
TI - Commentary on: Antibody and B Cell Responses to Plasmodium Sporozoites.
PMID- 25852687
TI - DFS70/LEDGFp75: An Enigmatic Autoantigen at the Interface between Autoimmunity,
AIDS, and Cancer.
AB - Clinical and diagnostic laboratories often encounter patient sera containing
antinuclear antibodies (ANAs) that produce a nuclear dense fine speckled
immunofluorescence pattern on HEp-2 cells. These autoantibodies usually target
the dense fine speckled protein of 70 kDa (DFS70), commonly known as lens
epithelium-derived growth factor p75 (LEDGFp75). Anti-DFS70/LEDGFp75
autoantibodies have recently attracted much interest because of their relatively
common occurrence in sera from patients with positive ANA tests with no clinical
evidence of systemic autoimmune rheumatic disease (SARD). Their presence has been
documented primarily in patients with diverse non-SARD inflammatory conditions
and "apparently healthy" individuals. While there is circumstantial evidence that
depending on the context these autoantibodies could play protective, pathogenic,
or sensor roles, their significance remains elusive. DFS70/LEDGFp75 has emerged
during the past decade as a stress transcription co-activator relevant to HIV
integration, cancer, and inflammation. It is not clear, however, what makes this
protein the target of such a common autoantibody response. We suggest that a
better understanding of DFS70/LEDGFp75 biology is key to elucidating the
significance of its associated autoantibodies. Here, we discuss briefly our
current understanding of this enigmatic autoantigen and potential scenarios
leading to its targeting by the immune system.
PMID- 25852686
TI - An evolutionary history of defensins: a role for copy number variation in
maximizing host innate and adaptive immune responses.
AB - Defensins represent an evolutionary ancient family of antimicrobial peptides that
play diverse roles in human health and disease. Defensins are cationic cysteine
containing multifunctional peptides predominantly expressed by epithelial cells
or neutrophils. Defensins play a key role in host innate immune responses to
infection and, in addition to their classically described role as antimicrobial
peptides, have also been implicated in immune modulation, fertility, development,
and wound healing. Aberrant expression of defensins is important in a number of
inflammatory diseases as well as modulating host immune responses to bacteria,
unicellular pathogens, and viruses. In parallel with their role in immunity, in
other species, defensins have evolved alternative functions, including the
control of coat color in dogs. Defensin genes reside in complex genomic regions
that are prone to structural variations and some defensin family members exhibit
copy number variation (CNV). Structural variations have mediated, and continue to
influence, the diversification and expression of defensin family members. This
review highlights the work currently being done to better understand the genomic
architecture of the beta-defensin locus. It evaluates current evidence linking
defensin CNV to autoimmune disease (i.e., Crohn's disease and psoriasis) as well
as the contribution CNV has in influencing immune responses to HIV infection.
PMID- 25852688
TI - A Highly Focused Antigen Receptor Repertoire Characterizes gammadelta T Cells
That are Poised to Make IL-17 Rapidly in Naive Animals.
AB - Interleukin (IL)-17 plays a key role in immunity. In acute infections, a rapid IL
17 response must be induced without prior antigen exposure, and gammadelta T
cells are the major initial IL-17 producers. In fact, some gammadelta T cells
make IL-17 within hours after an immune challenge. These cells appear to acquire
the ability to respond to IL-1 and IL-23 and to make IL-17 naturally in naive
animals. They are known as the natural Tgammadelta17 (nTgammadelta17) cells. The
rapidity of the nTgammadelta17 response, and the apparent lack of explicit T cell
receptor (TCR) engagement for its induction have led to the view that this is a
cytokine (IL-1, IL-23)-mediated response. However, pharmacological inhibition or
genetic defects in TCR signaling drastically reduce the nTgammadelta17 response
and/or their presence. To better understand antigen recognition in this rapid IL
17 response, we analyzed the antigen receptor repertoire of IL-1R(+)/IL-23R(+)
gammadelta T cells, a proxy for nTgammadelta17 cells in naive animals directly ex
vivo, using a barcode-enabled high throughput single-cell TCR sequence analysis.
We found that regardless of their anatomical origin, these cells have a highly
focused TCR repertoire. In particular, the TCR sequences have limited V gene
combinations, little or no junctional diversity and much reduced or no N region
diversity. In contrast, IL-23R(-) cells at mucosal sites similar to most of the
splenic gammadelta T cells and small intestine epithelial gammadelta lymphocytes
expressed diverse TCRs. This remarkable commonality and restricted repertoire of
IL-1R(+)/IL-23R(+) gammadelta T cells underscores the importance of antigen
recognition in their establishment/function.
PMID- 25852682
TI - Vitamin D Actions on CD4(+) T Cells in Autoimmune Disease.
AB - This review summarizes and integrates research on vitamin D and CD4(+) T
lymphocyte biology to develop new mechanistic insights into the molecular
etiology of autoimmune disease. A deep understanding of molecular mechanisms
relevant to gene-environment interactions is needed to deliver etiology-based
autoimmune disease prevention and treatment strategies. Evidence linking
sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is
summarized to develop the thesis that vitamin D is the environmental factor that
most strongly influences autoimmune disease development. Evidence for CD4(+) T
cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol
signaling to CD4(+) T lymphocytes is summarized to support the thesis that
calcitriol is sunlight's main protective signal transducer in autoimmune disease
risk. Animal modeling and human mechanistic data are summarized to support the
view that vitamin D probably influences thymic negative selection, effector Th1
and Th17 pathogenesis and responsiveness to extrinsic cell death signals,
FoxP3(+)CD4(+) T-regulatory cell and CD4(+) T-regulatory cell type 1 (Tr1) cell
functions, and a Th1-Tr1 switch. The proposed Th1-Tr1 switch appears to bridge
two stable, self-reinforcing immune states, pro- and anti-inflammatory, each with
a characteristic gene regulatory network. The bi-stable switch would enable T
cells to integrate signals from pathogens, hormones, cell-cell interactions, and
soluble mediators and respond in a biologically appropriate manner. Finally,
unanswered questions and potentially informative future research directions are
highlighted to speed delivery of etiology-based strategies to reduce autoimmune
disease.
PMID- 25852689
TI - Adeno-Associated Viral Vectors at the Frontier between Tolerance and Immunity.
PMID- 25852690
TI - Killer B lymphocytes and their fas ligand positive exosomes as inducers of immune
tolerance.
AB - Induction of immune tolerance is a key process by which the immune system is
educated to modulate reactions against benign stimuli such as self-antigens and
commensal microbes. Understanding and harnessing the natural mechanisms of immune
tolerance may become an increasingly useful strategy for treating many types of
allergic and autoimmune diseases, as well as for improving the acceptance of
solid organ transplants. Our laboratory and others have been interested in the
natural ability of some B lymphocytes to express the death-inducing molecule Fas
ligand (FasL), and their ability to kill T helper (TH) lymphocytes. We have
recently shown that experimental transformation of human B cells by a non
replicative variant of Epstein-Barr virus (EBV) consistently resulted in high
expression of functional FasL protein. The production and release of FasL(+)
exosomes that co-expressed major histocompatibility complex (MHC) class II
molecules and had the capacity to kill antigen-specific TH cells was also
observed. Several lines of evidence indicate that FasL+ B cells and
FasL(+)MHCII(+) exosomes have important roles in natural immune tolerance and
have a great deal of therapeutic potential. Taken together, these findings
suggest that EBV-immortalized human B lymphoblastoid cell lines could be used as
cellular factories for FasL(+) exosomes, which would be employed to
therapeutically establish and/or regain immune tolerance toward specific
antigens. The goals of this review are to summarize current knowledge of the
roles of FasL(+) B cells and exosomes in immune regulation, and to suggest
methods of manipulating killer B cells and FasL(+) exosomes for clinical
purposes.
PMID- 25852692
TI - A New Scientific Paradigm may be Needed to Finally Develop an HIV Vaccine.
AB - The bulk of current HIV vaccine research is conducted within the infectious
disease paradigm that has been very successful in developing vaccines against
many other viral diseases. Different HIV vaccine concepts, based on the induction
of neutralizing antibodies and/or cell mediated immunity, have been developed and
clinically tested over the last 30 years, resulting in a few small successes and
many disappointments. As new scientific knowledge is obtained, HIV vaccine
concepts are constantly modified with the hope that the newly introduced tweaks
(or paradigm drifts) will provide the solution to one of the most difficult
challenges that modern biomedical research is confronting. Efficacy trials have
been critical in guiding HIV vaccine development. However, from the five phase
III efficacy trials conducted to date, only one (RV144) resulted in modest
efficacy. The results from RV144 were surprising in many ways, including the
identified putative correlates of protection (or risk), which did not include
neutralizing antibodies or cytotoxic T-cells. The solution to the HIV vaccine
challenge may very well come from approaches based on the current paradigm.
However, at the same time, out-of-the-paradigm ideas should be systematically
explored to complement the current efforts. New mechanisms are needed to identify
and support the innovative research that will hopefully accelerate the
development of an urgently needed HIV vaccine.
PMID- 25852691
TI - 4-methylumbelliferone treatment and hyaluronan inhibition as a therapeutic
strategy in inflammation, autoimmunity, and cancer.
AB - Hyaluronan (HA) is a prominent component of the extracellular matrix at many
sites of chronic inflammation, including type 1 diabetes (T1D), multiple
sclerosis, and numerous malignancies. Recent publications have demonstrated that
when HA synthesis is inhibited using 4-methylumbelliferone (4-MU), beneficial
effects are observed in several animal models of these diseases. Notably, 4-MU is
an already approved drug in Europe and Asia called "hymecromone" where it is used
to treat biliary spasm. However, there is uncertainty regarding how 4-MU
treatment provides benefit in these animal models and the potential long-term
consequences of HA inhibition. Here, we review what is known about how HA
contributes to immune dysregulation and tumor progression. Then, we review what
is known about 4-MU and hymecromone in terms of mechanism of action,
pharmacokinetics, and safety. Finally, we review recent studies detailing the use
of 4-MU to treat animal models of cancer and autoimmunity.
PMID- 25852693
TI - Liver-Stage Specific Response among Endemic Populations: Diet and Immunity.
AB - Developing effective anti-malarial vaccine has been a challenge for long. Various
factors including complex life cycle of parasite and lack of knowledge of stage
specific critical antigens are some of the reasons. Moreover, inadequate
understanding of the immune responses vis-a-vis sterile protection induced
naturally by Plasmodia infection has further compounded the problem. It has been
shown that people living in endemic areas take years to develop protective
immunity to blood stage infection. But hardly anyone believes that immunity to
liver-stage infection could be developed. Various experimental model studies
using attenuated parasite suggest that liver-stage immunity might exist among
endemic populations. This could be induced because of the attenuation of parasite
in liver by various compounds present in the diet of endemic populations.
PMID- 25852694
TI - A Diverse Repertoire of Human Immunoglobulin Variable Genes in a Chicken B Cell
Line is Generated by Both Gene Conversion and Somatic Hypermutation.
AB - Chicken immune responses to human proteins are often more robust than rodent
responses because of the phylogenetic relationship between the different species.
For discovery of a diverse panel of unique therapeutic antibody candidates,
chickens therefore represent an attractive host for human-derived targets. Recent
advances in monoclonal antibody technology, specifically new methods for the
molecular cloning of antibody genes directly from primary B cells, has ushered in
a new era of generating monoclonal antibodies from non-traditional host animals
that were previously inaccessible through hybridoma technology. However, such
monoclonals still require post-discovery humanization in order to be developed as
therapeutics. To obviate the need for humanization, a modified strain of chickens
could be engineered to express a human-sequence immunoglobulin variable region
repertoire. Here, human variable genes introduced into the chicken immunoglobulin
loci through gene targeting were evaluated for their ability to be recognized and
diversified by the native chicken recombination machinery that is present in the
B-lineage cell line DT40. After expansion in culture the DT40 population
accumulated genetic mutants that were detected via deep sequencing. Bioinformatic
analysis revealed that the human targeted constructs are performing as expected
in the cell culture system, and provide a measure of confidence that they will be
functional in transgenic animals.
PMID- 25852695
TI - The known unknowns of the human dendritic cell network.
AB - Dendritic cells (DCs) initiate and orient immune responses and comprise several
subsets that display distinct phenotypes and properties. Most of our knowledge of
DC subsets biology is based on mouse studies. In the past few years, the
alignment of the human DC network with the mouse DC network has been the focus of
much attention. Although comparative phenotypic and transcriptomic analysis have
shown a high level of homology between mouse and human DC subsets, significant
differences in phenotype and function have also been evidenced. Here, we review
recent advances in our understanding of the human DC network and discuss some
remaining gaps and future challenges of the human DC field.
PMID- 25852696
TI - Induction of Protective Immune Responses Against Schistosomiasis haematobium in
Hamsters and Mice Using Cysteine Peptidase-Based Vaccine.
AB - One of the major lessons we learned from the radiation-attenuated cercariae
vaccine studies is that protective immunity against schistosomiasis is dependent
on the induction of T helper (Th)1-/Th2-related immune responses. Since most
schistosome larval and adult-worm-derived molecules used for vaccination
uniformly induce a polarized Th1 response, it was essential to include a type 2
immune response-inducing molecule, such as cysteine peptidases, in the vaccine
formula. Here, we demonstrate that a single subcutaneous injection of Syrian
hamsters with 200 MUg active papain, 1 h before percutaneous exposure to 150
cercariae of Schistosoma haematobium, led to highly significant (P < 0.005)
reduction of >50% in worm burden and worm egg counts in intestine. Immunization
of hamsters with 20 MUg recombinant glyceraldehyde 3-phosphate dehydrogenase
(rSG3PDH) and 20 MUg 2-cys peroxiredoxin-derived peptide in a multiple antigen
peptide construct (PRX MAP) together with papain (20 MUg/hamster), as adjuvant
led to considerable (64%) protection against challenge S. haematobium infection,
similar to the levels reported with irradiated cercariae. Cysteine peptidases
based vaccination was also effective in protecting outbred mice against a
percutaneous challenge infection with S. haematobium cercariae. In two
experiments, a mixture of Schistosoma mansoni cathepsin B1 (SmCB1) and Fasciola
hepatica cathepsin L1 (FhCL1) led to highly significant (P < 0.005) reduction of
70% in challenge S. haematobium worm burden and 60% reduction in liver egg
counts. Mice vaccinated with SmCB1/FhCL1/rSG3PDH mixture and challenged with S.
haematobium cercariae 3 weeks after the second immunization displayed highly
significant (P < 0.005) reduction of 72% in challenge worm burden and no eggs in
liver of 8-10 mice/group, as compared to unimmunized mice, associated with
production of a mixture of type 1- and type 2-related cytokines and antibody
responses.
PMID- 25852697
TI - Behcet's Disease: Do Natural Killer Cells Play a Significant Role?
AB - Behcet's disease (BD) is a complex inflammatory disease, of unknown etiology.
While disease pathogenesis remains unclear, a strong relationship between BD and
HLA-B*51 has been established over the last 30 years. A number of theories exist
regarding the cause of BD; however, few are able to account for the increased
rates of HLA-B*51 positive individuals, particularly around the Mediterranean
basin and Middle-East where the prevalence is highest. This review outlines
current immunogenetic data on BD and the immunoregulatory role natural killer
cells may play. It also describes the interaction of the killer immunoglobulin
like receptor - KIR3DL1 with its ligand Bw4, which is found on HLA-B51. Finally,
CD94/NKG2D, MICA, and ERAP are outlined with regard to their potential roles in
BD.
PMID- 25852699
TI - Introgression of a rare haplotype from Southeastern Africa to breed California
blackeyes with larger seeds.
AB - Seed size distinguishes most crops from their wild relatives and is an important
quality trait for the grain legume cowpea. In order to breed cowpea varieties
with larger seeds we introgressed a rare haplotype associated with large seeds at
the Css-1 locus from an African buff seed type cultivar, IT82E-18 (18.5 g/100
seeds), into a blackeye seed type cultivar, CB27 (22 g/100 seed). Four
recombinant inbred lines derived from these two parents were chosen for marker
assisted breeding based on SNP genotyping with a goal of stacking large seed
haplotypes into a CB27 background. Foreground and background selection were
performed during two cycles of backcrossing based on genome-wide SNP markers. The
average seed size of introgression lines homozygous for haplotypes associated
with large seeds was 28.7g/100 seed and 24.8 g/100 seed for cycles 1 and 2,
respectively. One cycle 1 introgression line with desirable seed quality was
selfed for two generations to make families with very large seeds (28-35 g/100
seeds). Field-based performance trials helped identify breeding lines that not
only have large seeds but are also desirable in terms of yield, maturity, and
plant architecture when compared to industry standards. A principal component
analysis was used to explore the relationships between the parents relative to a
core set of landraces and improved varieties based on high-density SNP data. The
geographic distribution of haplotypes at the Css-1 locus suggest the haplotype
associated with large seeds is unique to accessions collected from Southeastern
Africa. Therefore this quantitative trait locus has a strong potential to develop
larger seeded varieties for other growing regions which is demonstrated in this
work using a California pedigree.
PMID- 25852698
TI - Transcriptomic profiling of linolenic acid-responsive genes in ROS signaling from
RNA-seq data in Arabidopsis.
AB - Linolenic acid (Ln) released from chloroplast membrane galactolipids is a
precursor of the phytohormone jasmonic acid (JA). The involvement of this hormone
in different plant biological processes, such as responses to biotic stress
conditions, has been extensively studied. However, the role of Ln in the
regulation of gene expression during abiotic stress situations mediated by
cellular redox changes and/or by oxidative stress processes remains poorly
understood. An RNA-seq approach has increased our knowledge of the interplay
among Ln, oxidative stress and ROS signaling that mediates abiotic stress
conditions. Transcriptome analysis with the aid of RNA-seq in the absence of
oxidative stress revealed that the incubation of Arabidopsis thaliana cell
suspension cultures (ACSC) with Ln resulted in the modulation of 7525 genes, of
which 3034 genes had a 2-fold-change, being 533 up- and 2501 down-regulated
genes, respectively. Thus, RNA-seq data analysis showed that an important set of
these genes were associated with the jasmonic acid biosynthetic pathway including
lypoxygenases (LOXs) and Allene oxide cyclases (AOCs). In addition, several
transcription factor families involved in the response to biotic stress
conditions (pathogen attacks or herbivore feeding), such as WRKY, JAZ, MYC, and
LRR were also modified in response to Ln. However, this study also shows that Ln
has the capacity to modulate the expression of genes involved in the response to
abiotic stress conditions, particularly those mediated by ROS signaling. In this
regard, we were able to identify new targets such as galactinol synthase 1
(GOLS1), methionine sulfoxide reductase (MSR) and alkenal reductase in ACSC. It
is therefore possible to suggest that, in the absence of any oxidative stress, Ln
is capable of modulating new sets of genes involved in the signaling mechanism
mediated by additional abiotic stresses (salinity, UV and high light intensity)
and especially in stresses mediated by ROS.
PMID- 25852700
TI - Production of genetically and developmentally modified seaweeds: exploiting the
potential of artificial selection techniques.
AB - Plant feedstock with specific, modified developmental features has been a quest
for centuries. Since the development and spread of agriculture, there has been a
desire for plants producing disproportionate-or more abundant and more
nutritional-biomass that meet human needs better than their native counterparts.
Seaweed aquaculture, targeted for human consumption and the production of various
raw materials, is a rapidly expanding field and its stakeholders have increasing
vested interest for cost-effective and lucrative seaweed cultivation processes.
Thus, scientific research on seaweed development is particularly timely: the
potential for expansion of seaweed cultivation depends on the sector's capacity
to produce seaweeds with modified morphological features (e.g., thicker blades),
higher growth rates or delayed (or even no) fertility. Here, we review the
various technical approaches used to modify development in macroalgae, which have
attracted little attention from developmental biologists to date. Because seaweed
(or marine macroalgae) anatomy is much less complex than that of land plants and
because seaweeds belong to three different eukaryotic phyla, the mechanisms
controlling their morphogenesis are key to understanding their development. Here,
we present efficient sources of developmentally and genetically modified seaweeds
somatic variants, artificial hybrids and mutants-as well as the future potential
of these techniques.
PMID- 25852701
TI - Proteome readjustments in the apoplastic space of Arabidopsis thaliana ggt1
mutant leaves exposed to UV-B radiation.
AB - Ultraviolet-B radiation acts as an environmental stimulus, but in high doses it
has detrimental effects on plant metabolism. Plasma membranes represent a major
target for Reactive Oxygen Species (ROS) generated by this harmful radiation.
Oxidative reactions occurring in the apoplastic space are counteracted by
antioxidative systems mainly involving ascorbate and, to some extent,
glutathione. The occurrence of the latter and its exact role in the extracellular
space are not well documented, however. In Arabidopsis thaliana, the gamma
glutamyl transferase isoform (GGT1) bound to the cell wall takes part in the so
called gamma-glutamyl cycle for extracellular glutathione degradation and
recovery, and may be implicated in redox sensing and balance. In this work,
oxidative conditions were imposed with Ultraviolet-B radiation (UV-B) and studied
in redox altered ggt1 mutants. The response of ggt1 knockout Arabidopsis leaves
to UV-B radiation was assessed by investigating changes in extracellular
glutathione and ascorbate content and their redox state, and in apoplastic
protein composition. Our results show that, on UV-B exposure, soluble
antioxidants respond to the oxidative conditions in both genotypes.
Rearrangements occur in their apoplastic protein composition, suggesting an
involvement of Hydrogen Peroxide (H2O2), which may ultimately act as a signal.
Other important changes relating to hormonal effects, cell wall remodeling, and
redox activities are discussed. We argue that oxidative stress conditions imposed
by UV-B and disruption of the gamma-glutamyl cycle result in similar stress
induced responses, to some degree at least. Data are available via
ProteomeXchange with identifier PXD001807.
PMID- 25852702
TI - Stable heterologous expression of biologically active terpenoids in green plant
cells.
AB - Plants biosynthesize a great diversity of biologically active small molecules of
interest for fragrances, flavors, and pharmaceuticals. Among specialized
metabolites, terpenoids represent the greatest molecular diversity. Many
terpenoids are very complex, and total chemical synthesis often requires many
steps and difficult chemical reactions, resulting in a low final yield or
incorrect stereochemistry. Several drug candidates with terpene skeletons are
difficult to obtain by chemical synthesis due to their large number of chiral
centers. Thus, biological production remains the preferred method for industrial
production for many of these compounds. However, because these chemicals are
often found in low abundance in the native plant, or are produced in plants which
are difficult to cultivate, there is great interest in engineering increased
production or expression of the biosynthetic pathways in heterologous hosts.
Although there are many examples of successful engineering of microbes such as
yeast or bacteria to produce these compounds, this often requires extensive
changes to the host organism's metabolism. Optimization of plant gene expression,
post-translational protein modifications, subcellular localization, and other
factors often present challenges. To address the future demand for natural
products used as drugs, new platforms are being established that are better
suited for heterologous production of plant metabolites. Specifically, direct
metabolic engineering of plants can provide effective heterologous expression for
production of valuable plant-derived natural products. In this review, our
primary focus is on small terpenoids and we discuss the benefits of plant
expression platforms and provide several successful examples of stable production
of small terpenoids in plants.
PMID- 25852703
TI - Biofortification and phytoremediation of selenium in China.
AB - Selenium (Se) is an essential trace element for humans and animals but at high
concentrations, Se becomes toxic to organisms due to Se replacing sulfur in
proteins. Selenium biofortification is an agricultural process that increases the
accumulation of Se in crops, through plant breeding, genetic engineering, or use
of Se fertilizers. Selenium phytoremediation is a green biotechnology to clean up
Se-contaminated environments, primarily through phytoextraction and
phytovolatilization. By integrating Se phytoremediation and biofortification
technologies, Se-enriched plant materials harvested from Se phytoremediation can
be used as Se-enriched green manures or other supplementary sources of Se for
producing Se-biofortified agricultural products. Earlier studies primarily aimed
at enhancing efficacy of phytoremediation and biofortification of Se based on
natural variation in progenitor or identification of unique plant species. In
this review, we discuss promising approaches to improve biofortification and
phytoremediation of Se using knowledge acquired from model crops. We also
explored the feasibility of applying biotechnologies such as inoculation of
microbial strains for improving the efficiency of biofortification and
phytoremediation of Se. The key research and practical challenges that remain in
improving biofortification and phytoremediation of Se have been highlighted, and
the future development and uses of Se-biofortified agricultural products in China
has also been discussed.
PMID- 25852704
TI - Cottonseed protein, oil, and mineral status in near-isogenic Gossypium hirsutum
cotton lines expressing fuzzy/linted and fuzzless/linted seed phenotypes under
field conditions.
AB - Cotton is an important crop in the world and is a major source of oil for human
consumption and cotton meal for livestock. Cottonseed nutrition (seed
composition: protein, oil, and minerals) determines the quality of seeds.
Therefore, maintaining optimum levels of cottonseed nutrition is critical.
Physiological and genetic mechanisms controlling the levels of these constituents
in cottonseed are still largely unknown. Our previous research conducted under
greenhouse conditions showed that seed and leaf nutrition differed between
fuzzless and fuzzy seed isolines. Therefore, the objective of this research was
to investigate the seed fuzz phenotype (trait) effects on seed protein, oil, N,
C, S, and minerals in five sets of near-isogenic mutant cotton lines for seed
fuzz in a 2-year experiment under field condition to evaluate the stability of
the effect of the trait on seed nutrition. The isolines (genotypes) in each set
differ for the seed fuzz trait (fuzzless/linted seed line, N lines, and
fuzzy/linted seed line, F lines). Results showed that seed protein was higher in
the fuzzy genotype in all sets, but seed oil was higher in fuzzless genotype in
all sets. The concentrations of seed Ca and C were higher in all fuzzless
genotypes, but N, S, B, Fe, and Zn were higher in most of the fuzzy genotypes.
Generally, minerals were higher in leaves of F lines, suggesting the
translocation of minerals from leaves to seeds was limited. The research
demonstrated that fiber development could be involved in cottonseed composition.
This may be due to the involvement of fiber development in carbon and nitrogen
metabolism, and the mobility of nutrients from leaves (source) to seed (sink).
This information is beneficial to breeders to consider fuzzless cottonseed for
potential protein and oil use and select for higher oil or higher protein
content, and to physiologists to further understand the mobility of minerals to
increase the quality of cottonseed nutrition for food and feed.
PMID- 25852705
TI - Understanding litter decomposition in semiarid ecosystems: linking leaf traits,
UV exposure and rainfall variability.
AB - Differences in litter quality, microbial activity or abiotic conditions cannot
fully account for the variability in decomposition rates observed in semiarid
ecosystems. Here we tested the role of variation in litter quality, water supply,
and UV radiation as drivers of litter decomposition in arid lands. And show that
carry-over effects of litter photodegradation during dry periods can regulate
decomposition during subsequent wet periods. We present data from a two-phase
experiment, where we first exposed litter from a drought-deciduous and an
evergreen shrub to natural UV levels during five, rainless summer months and,
subsequently, in the laboratory, we assessed the carry-over effects of
photodegradation on biomass loss under different irrigation treatments
representing the observed range of local rainfall variation among years (15-240
mm). Photodegradation of litter in the field produced average carbon losses of
12%, but deciduous Proustia pungens lost >25%, while evergreen Porlieria
chilensis less than 5%. Natural exposure to UV significantly reduced carbon-to
nitrogen and lignin:N ratios in Proustia litter but not in Porlieria. During the
subsequent wet phase, remaining litter biomass was lower in Proustia than in
Porlieria. Indeed UV exposure increased litter decomposition of Proustia under
low and medium rainfall treatments, whereas no carry-over effects were detected
under high rainfall treatment. Consequently, for deciduous Proustia carry-over
effects of UV exposure were negligible under high irrigation. Litter
decomposition of the evergreen Porlieria depended solely on levels of rainfall
that promote microbial decomposers. Our two-phase experiment revealed that both
the carry-over effects of photodegradation and litter quality, modulated by inter
annual variability in rainfall, can explain the marked differences in
decomposition rates and the frequent decoupling between rainfall and litter
decomposition observed in semiarid ecosystems.
PMID- 25852706
TI - Uncovering the genetic architecture of Colletotrichum lindemuthianum resistance
through QTL mapping and epistatic interaction analysis in common bean.
AB - Colletotrichum lindemuthianum is a hemibiotrophic fungal pathogen that causes
anthracnose disease in common bean. Despite the genetics of anthracnose
resistance has been studied for a long time, few quantitative trait loci (QTLs)
studies have been conducted on this species. The present work examines the
genetic basis of quantitative resistance to races 23 and 1545 of C.
lindemuthianum in different organs (stem, leaf and petiole). A population of 185
recombinant inbred lines (RIL) derived from the cross PMB0225 * PHA1037 was
evaluated for anthracnose resistance under natural and artificial photoperiod
growth conditions. Using multi-environment QTL mapping approach, 10 and 16 main
effect QTLs were identified for resistance to anthracnose races 23 and 1545,
respectively. The homologous genomic regions corresponding to 17 of the 26 main
effect QTLs detected were positive for the presence of resistance-associated gene
cluster encoding nucleotide-binding and leucine-rich repeat (NL) proteins. Among
them, it is worth noting that the main effect QTLs detected on linkage group 05
for resistance to race 1545 in stem, petiole and leaf were located within a 1.2
Mb region. The NL gene Phvul.005G117900 is located in this region, which can be
considered an important candidate gene for the non-organ-specific QTL identified
here. Furthermore, a total of 39 epistatic QTL (E-QTLs) (21 for resistance to
race 23 and 18 for resistance to race 1545) involved in 20 epistatic interactions
(eleven and nine interactions for resistance to races 23 and 1545, respectively)
were identified. None of the main and epistatic QTLs detected displayed
significant environment interaction effects. The present research provides
essential information not only for the better understanding of the plant-pathogen
interaction but also for the application of genomic assisted breeding for
anthracnose resistance improvement in common bean through application of marker
assisted selection (MAS).
PMID- 25852707
TI - Protein profile of Beta vulgaris leaf apoplastic fluid and changes induced by Fe
deficiency and Fe resupply.
AB - The fluid collected by direct leaf centrifugation has been used to study the
proteome of the sugar beet apoplastic fluid as well as the changes induced by Fe
deficiency and Fe resupply to Fe-deficient plants in the protein profile. Plants
were grown in Fe-sufficient and Fe-deficient conditions, and Fe resupply was
carried out with 45 MUM Fe(III)-EDTA for 24 h. Protein extracts of leaf
apoplastic fluid were analyzed by two-dimensional isoelectric focusing-SDS-PAGE
electrophoresis. Gel image analysis revealed 203 consistent spots, and proteins
in 81% of them (164) were identified by nLC-MS/MS using a custom made reference
repository of beet protein sequences. When redundant UniProt entries were
deleted, a non-redundant leaf apoplastic proteome consisting of 109 proteins was
obtained. TargetP and SecretomeP algorithms predicted that 63% of them were
secretory proteins. Functional classification of the non-redundant proteins
indicated that stress and defense, protein metabolism, cell wall and C metabolism
accounted for approximately 75% of the identified proteome. The effects of Fe
deficiency on the leaf apoplast proteome were limited, with only five spots
(2.5%) changing in relative abundance, thus suggesting that protein homeostasis
in the leaf apoplast fluid is well-maintained upon Fe shortage. The
identification of three chitinase isoforms among proteins increasing in relative
abundance with Fe-deficiency suggests that one of the few effects of Fe
deficiency in the leaf apoplast proteome includes cell wall modifications. Iron
resupply to Fe deficient plants changed the relative abundance of 16 spots when
compared to either Fe-sufficient or Fe-deficient samples. Proteins identified in
these spots can be broadly classified as those responding to Fe-resupply, which
included defense and cell wall related proteins, and non-responsive, which are
mainly protein metabolism related proteins and whose changes in relative
abundance followed the same trend as with Fe-deficiency.
PMID- 25852709
TI - Auxin metabolism rates and implications for plant development.
AB - Studies of auxin metabolism rarely express their results as a metabolic rate,
although the data obtained would often permit such a calculation to be made. We
analyze data from 31 previously published papers to quantify the rates of auxin
biosynthesis, conjugation, conjugate hydrolysis, and catabolism in seed plants.
Most metabolic pathways have rates in the range 10 nM/h-1 MUM/h, with the
exception of auxin conjugation, which has rates as high as ~100 MUM/h. The high
rates of conjugation suggest that auxin metabolic sinks may be very small,
perhaps as small as a single cell. By contrast, the relatively low rate of auxin
biosynthesis requires plants to conserve and recycle auxin during long-distance
transport. The consequences for plant development are discussed.
PMID- 25852708
TI - An update on polygalacturonase-inhibiting protein (PGIP), a leucine-rich repeat
protein that protects crop plants against pathogens.
AB - Polygalacturonase inhibiting proteins (PGIPs) are cell wall proteins that inhibit
the pectin-depolymerizing activity of polygalacturonases secreted by microbial
pathogens and insects. These ubiquitous inhibitors have a leucine-rich repeat
structure that is strongly conserved in monocot and dicot plants. Previous
reviews have summarized the importance of PGIP in plant defense and the
structural basis of PG-PGIP interaction; here we update the current knowledge
about PGIPs with the recent findings on the composition and evolution of pgip
gene families, with a special emphasis on legume and cereal crops. We also update
the information about the inhibition properties of single pgip gene products
against microbial PGs and the results, including field tests, showing the
capacity of PGIP to protect crop plants against fungal, oomycetes and bacterial
pathogens.
PMID- 25852710
TI - Genetic diversity and genomic resources available for the small millet crops to
accelerate a New Green Revolution.
AB - Small millets are nutrient-rich food sources traditionally grown and consumed by
subsistence farmers in Asia and Africa. They include finger millet (Eleusine
coracana), foxtail millet (Setaria italica), kodo millet (Paspalum
scrobiculatum), proso millet (Panicum miliaceum), barnyard millet (Echinochloa
spp.), and little millet (Panicum sumatrense). Local farmers value the small
millets for their nutritional and health benefits, tolerance to extreme stress
including drought, and ability to grow under low nutrient input conditions, ideal
in an era of climate change and steadily depleting natural resources. Little
scientific attention has been paid to these crops, hence they have been termed
"orphan cereals." Despite this challenge, an advantageous quality of the small
millets is that they continue to be grown in remote regions of the world which
has preserved their biodiversity, providing breeders with unique alleles for crop
improvement. The purpose of this review, first, is to highlight the diverse
traits of each small millet species that are valued by farmers and consumers
which hold potential for selection, improvement or mechanistic study. For each
species, the germplasm, genetic and genomic resources available will then be
described as potential tools to exploit this biodiversity. The review will
conclude with noting current trends and gaps in the literature and make
recommendations on how to better preserve and utilize diversity within these
species to accelerate a New Green Revolution for subsistence farmers in Asia and
Africa.
PMID- 25852711
TI - Antioxidant response and related gene expression in aged oat seed.
AB - To evaluate deterioration of oat seeds during storage, we analyzed oxygen
radicals, antioxidant enzyme activity, proline content, and gene transcript
levels in oat seeds with different moisture contents (MCs; 4, 16, and 28% w/w)
during storage for 0, 6, and 12 months (CK, LT-6, and LT-12 treatments,
respectively) at 4 degrees C. The germination percentage decreased significantly
with higher seed MCs and longer storage duration. The concentrations of
superoxide radical and hydrogen peroxide increased with seed MC increasing. The
activities of catalase (CAT), ascorbate peroxidase (APX), and superoxide
dismutase (SOD) may have had a complementary or interacting role to scavenge
reactive oxygen species. As the storage duration extended, the proline content
decreased in seeds with 4 and 16% MC and increased in 28%. These findings suggest
that proline played the main role in adaptation to oxidative stress in seeds with
higher MC (28%), while antioxidant enzymes played the main role in seeds with
lower MCs (4%, 16%). In the gene transcript analyses, SOD1 transcript levels were
not consistent with total SOD activity. The transcript levels of APX1 and CAT1
showed similar trends to those of APX and CAT activity. The transcript levels of
P5CS1, which encodes a proline biosynthetic enzyme, increased with seed MC
increasing in CK. Compared with changing of proline content in seeds stored 12
months, PDH1 transcript levels showed the opposite trend and maintained the lower
levels in seeds of 16 and 28% MCs. The transcript level of P5CS1 was
significantly affected by MC, and PDH1 could improve stress resistance for seed
aging and maintain seed vigor during long-term storage.
PMID- 25852712
TI - Arabidopsis histone demethylases LDL1 and LDL2 control primary seed dormancy by
regulating DELAY OF GERMINATION 1 and ABA signaling-related genes.
AB - Seed dormancy controls germination and plays a critical role in regulating the
beginning of the life cycle of plants. Seed dormancy is established and
maintained during seed maturation and is gradually broken during dry storage
(after-ripening). The plant hormone abscisic acid (ABA) and DELAY OF GERMINATION1
(DOG1) protein are essential regulators of seed dormancy. Recent studies revealed
that chromatin modifications are also involved in the transcription regulation of
seed dormancy. Here, we showed that two Arabidopsis histone demethylases,
LYSINESPECIFIC DEMETHYLASE LIKE 1 and 2 (LDL1 and LDL2) act redundantly in
repressing of seed dormancy. LDL1 and LDL2 are highly expressed in the early
silique developing stage. The ldl1 ldl2 double mutant displays increased seed
dormancy, whereas overexpression of LDL1 or LDL2 in Arabidopsis causes reduced
dormancy. Furthermore, we showed that LDL1 and LDL2 repress the expression of
seed dormancy-related genes, including DOG1, ABA2 and ABI3 during seed dormancy
establishment. Furthermore, genetic analysis revealed that the repression of seed
dormancy by LDL1 and LDL2 requires DOG1, ABA2, and ABI3. Taken together, our
findings revealed that LDL1 and LDL2 play an essential role in seed dormancy.
PMID- 25852713
TI - The use of the ph1b mutant to induce recombination between the chromosomes of
wheat and barley.
AB - Intensive breeding has led to a narrowing in the genetic base of our major crops.
In wheat, access to the extensive gene pool residing in its many and varied
relatives (some cultivated, others wild) is hampered by the block on
recombination imposed by the Ph1 (Pairing homoeologous 1) gene. Here, the ph1b
mutant has been exploited to induced allosyndesis between wheat chromosomes and
those of both Hordeum vulgare (cultivated barley) and H. chilense (a wild
barley). A number of single chromosome Hordeum sp. substitution and addition
lines in wheat were crossed and backcrossed to the ph1b mutant to produce plants
in which pairing between the wheat and the non-wheat chromosomes was not
suppressed by the presence of Ph1. Genomic in situ hybridization was applied to
almost 500 BC1F2 progeny as a screen for allosyndetic recombinants. Chromosome
rearrangements were detected affecting H. chilense chromosomes 4H (ch) , 5H (ch)
, 6H (ch) , and 7H (ch) and H. vulgare chromosomes 4H (v) , 6H (v) , and 7H (v) .
Two of these were clearly the product of a recombination event involving
chromosome 4H (ch) and a wheat chromosome.
PMID- 25852714
TI - Dynamics of long-distance signaling via plant vascular tissues.
AB - Plant vascular systems are constructed by specific cell wall modifications
through which cells are highly specialized to make conduits for water and
nutrients. Xylem vessels are formed by thickened cell walls that remain after
programmed cell death, and serve as water conduits from the root to the shoot. In
contrast, phloem tissues consist of a complex of living cells, including sieve
tube elements and their neighboring companion cells, and translocate
photosynthetic assimilates from mature leaves to developing young tissues.
Intensive studies on the content of vascular flow fluids have unveiled that plant
vascular tissues transport various types of gene product, and the transport of
some provides the molecular basis for the long-distance communications. Analysis
of xylem sap has demonstrated the presence of proteins in the xylem transpiration
stream. Recent studies have revealed that CLE and CEP peptides secreted in the
roots are transported to above ground via the xylem in response to plant-microbe
interaction and soil nitrogen starvation, respectively. Their leucine-rich repeat
transmembrane receptors localized in the shoot phloem are required for relaying
the signal from the shoot to the root. These findings well-fit to the current
scenario of root-to-shoot-to-root feedback signaling, where peptide transport
achieves the root-to-shoot signaling, the first half of the signaling process.
Meanwhile, it is now well-evidenced that proteins and a range of RNAs are
transported via the phloem translocation system, and some of those can exert
their physiological functions at their destinations, including roots. Thus, plant
vascular systems may serve not only as conduits for the translocation of
essential substances but also as long-distance communication pathways that allow
plants to adapt to changes in internal and external environments at the whole
plant level.
PMID- 25852716
TI - Metabolic engineering of medium-chain fatty acid biosynthesis in Nicotiana
benthamiana plant leaf lipids.
AB - Various research groups are investigating the production of oil in non-seed
biomass such as leaves. Recently, high levels of oil accumulation have been
achieved in plant biomass using a combination of biotechnological approaches
which also resulted in significant changes to the fatty acid composition of the
leaf oil. In this study, we were interested to determine whether medium-chain
fatty acids (MCFA) could be accumulated in leaf oil. MCFA are an ideal feedstock
for biodiesel and a range of oleochemical products including lubricants,
coatings, and detergents. In this study, we explore the synthesis, accumulation,
and glycerolipid head-group distribution of MCFA in leaves of Nicotiana
benthamiana after transient transgenic expression of C12:0-, C14:0-, and C16:0
ACP thioesterase genes. We demonstrate that the production of these MCFA in leaf
is increased by the co-expression of the WRINKLED1 (WRI1) transcription factor,
with the lysophosphatidic acid acyltransferase (LPAAT) from Cocos nucifera being
required for the assembly of tri-MCFA TAG species. We also demonstrate that the
newly-produced MCFA are incorporated into the triacylglycerol of leaves in which
WRI1 + diacylglycerol acyltransferase1 (DGAT1) genes are co-expressed for
increased oil accumulation.
PMID- 25852717
TI - Sensitivity of cold acclimation to elevated autumn temperature in field-grown
Pinus strobus seedlings.
AB - Climate change will increase autumn air temperature, while photoperiod decrease
will remain unaffected. We assessed the effect of increased autumn air
temperature on timing and development of cold acclimation and freezing resistance
in Eastern white pine (EWP, Pinus strobus) under field conditions. For this
purpose we simulated projected warmer temperatures for southern Ontario in a
Temperature Free-Air-Controlled Enhancement (T-FACE) experiment and exposed EWP
seedlings to ambient (Control) or elevated temperature (ET, +1.5 degrees C/+3
degrees C during day/night). Photosynthetic gas exchange, chlorophyll
fluorescence, photoprotective pigments, leaf non-structural carbohydrates (NSC),
and cold hardiness were assessed over two consecutive autumns. Nighttime
temperature below 10 degrees C and photoperiod below 12 h initiated
downregulation of assimilation in both treatments. When temperature further
decreased to 0 degrees C and photoperiod became shorter than 10 h, downregulation
of the light reactions and upregulation of photoprotective mechanisms occurred in
both treatments. While ET seedlings did not delay the timing of the
downregulation of assimilation, stomatal conductance in ET seedlings was
decreased by 20-30% between August and early October. In both treatments leaf NSC
composition changed considerably during autumn but differences between Control
and ET seedlings were not significant. Similarly, development of freezing
resistance was induced by exposure to low temperature during autumn, but the
timing was not delayed in ET seedlings compared to Control seedlings. Our results
indicate that EWP is most sensitive to temperature changes during October and
November when downregulation of photosynthesis, enhancement of photoprotection,
synthesis of cold-associated NSCs and development of freezing resistance occur.
However, we also conclude that the timing of the development of freezing
resistance in EWP seedlings is not affected by moderate temperature increases
used in our field experiments.
PMID- 25852718
TI - Transcriptomic insights into antagonistic effects of gibberellin and abscisic
acid on petal growth in Gerbera hybrida.
AB - Petal growth is central to floral morphogenesis, but the underlying genetic basis
of petal growth regulation is yet to be elucidated. In this study, we found that
the basal region of the ray floret petals of Gerbera hybrida was the most
sensitive to treatment with the phytohormones gibberellin (GA) and abscisic acid
(ABA), which regulate cell expansion during petal growth in an antagonistic
manner. To screen for differentially expressed genes (DEGs) and key regulators
with potentially important roles in petal growth regulation by GA or/and ABA, the
RNA-seq technique was employed. Differences in global transcription in petals
were observed in response to GA and ABA and target genes antagonistically
regulated by the two hormones were identified. Moreover, we also identified the
pathways associated with the regulation of petal growth after application of
either GA or ABA. Genes relating to the antagonistic GA and ABA regulation of
petal growth showed distinct patterns, with genes encoding transcription factors
(TFs) being active during the early stage (2 h) of treatment, while genes from
the "apoptosis" and "cell wall organization" categories were expressed at later
stages (12 h). In summary, we present the first study of global expression
patterns of hormone-regulated transcripts in G. hybrida petals; this dataset will
be instrumental in revealing the genetic networks that govern petal morphogenesis
and provides a new theoretical basis and novel gene resources for ornamental
plant breeding.
PMID- 25852719
TI - Recent developments in fast spectroscopy for plant mineral analysis.
AB - Ideal fertilizer management to optimize plant productivity and quality is more
relevant than ever, as global food demands increase along with the rapidly
growing world population. At the same time, sub-optimal or excessive use of
fertilizers leads to severe environmental damage in areas of intensive crop
production. The approaches of soil and plant mineral analysis are briefly
compared and discussed here, and the new techniques using fast spectroscopy that
offer cheap, rapid, and easy-to-use analysis of plant nutritional status are
reviewed. The majority of these methods use vibrational spectroscopy, such as
visual-near infrared and to a lesser extent ultraviolet and mid-infrared
spectroscopy. Advantages of and problems with application of these techniques are
thoroughly discussed. Spectroscopic techniques considered having major potential
for plant mineral analysis, such as chlorophyll a fluorescence, X-ray
fluorescence, and laser-induced breakdown spectroscopy are also described.
PMID- 25852715
TI - Osmotin: a plant sentinel and a possible agonist of mammalian adiponectin.
AB - Osmotin is a stress responsive antifungal protein belonging to the pathogenesis
related (PR)-5 family that confers tolerance to both biotic and abiotic stresses
in plants. Protective efforts of osmotin in plants range from high temperature to
cold and salt to drought. It lyses the plasma membrane of the pathogens. It is
widely distributed in fruits and vegetables. It is a differentially expressed and
developmentally regulated protein that protects the cells from osmotic stress and
invading pathogens as well, by structural or metabolic alterations. During stress
conditions, osmotin helps in the accumulation of the osmolyte proline, which
quenches reactive oxygen species and free radicals. Osmotin expression results in
the accumulation of storage reserves and increases the shelf-life of fruits. It
binds to a seven-transmembrane-domain receptor-like protein and induces
programmed cell death in Saccharomyces cerevisiae through RAS2/cAMP signaling
pathway. Adiponectin, produced in adipose tissues of mammals, is an insulin
sensitizing hormone. Strangely, osmotin acts like the mammalian hormone
adiponectin in various in vitro and in vivo models. Adiponectin and osmotin, the
two receptor binding proteins do not share sequence similarity at the amino acid
level, but interestingly they have a similar structural and functional
properties. In experimental mice, adiponectin inhibits endothelial cell
proliferation and migration, primary tumor growth, and reduces atherosclerosis.
This retrospective work examines the vital role of osmotin in plant defense and
as a potential targeted therapeutic drug for humans.
PMID- 25852721
TI - Crown traits of coniferous trees and their relation to shade tolerance can differ
with leaf type: a biophysical demonstration using computed tomography scanning
data.
AB - Plant light interception and shade tolerance are intrinsically related in that
they involve structural, morphological and physiological adaptations to manage
light capture for photosynthetic utilization, in order to sustain survival,
development and reproduction. At the scale of small-size trees, crown traits
related to structural geometry of branching pattern and space occupancy through
phyllotaxis can be accurately evaluated in 3D, using computed tomography (CT)
scanning data. We demonstrate this by scrutinizing the crowns of 15 potted
miniature conifers of different species or varieties, classified in two groups
based on leaf type (10 needlelike, 5 scalelike); we also test whether mean values
of crown traits measured from CT scanning data and correlations with a shade
tolerance index (STI) differ between groups. Seven crown traits, including
fractal dimensions (FD1: smaller scales, FD2: larger scales) and leaf areas, were
evaluated for all 15 miniature conifers; an average silhouette-to-total-area
ratio was also calculated for each of the 10 needlelike-leaf conifers. Between
group differences in mean values are significant (P < 0.05) for STI, FD1, FD2,
and the average leaf area displayed (AD). Between-group differences in sign and
strength of correlations are observed. For example, the correlation between STI
and FD1 is negative and significant (P < 0.10) for the needlelike-leaf group, but
is positive and significant (P < 0.05) for the miniature conifers with scalelike
leaves, which had lower STI and higher FD1 on average in our study; the positive
correlation between STI and AD is significant (P < 0.05) for the scalelike-leaf
group, and very moderate for the needlelike-leaf one. A contrasting physical
attachment of the leaves to branches may explain part of the between-group
differences. Our findings open new avenues for the understanding of fundamental
plant growth processes; the information gained could be included in a multi-scale
approach to tree crown modeling.
PMID- 25852720
TI - Salicylic acid and reactive oxygen species interplay in the transcriptional
control of defense genes expression.
AB - It is well established that salicylic acid (SA) plays a critical role in the
transcriptional reprograming that occurs during the plant defense response
against biotic and abiotic stress. In the course of the defense response, the
transcription of different sets of defense genes is controlled in a spatio
temporal manner via SA-mediated mechanisms. Interestingly, different lines of
evidence indicate that SA interplays with reactive oxygen species (ROS) and
glutathione (GSH) in stressed plants. In this review we focus on the evidence
that links SA, ROS, and GSH signals to the transcriptional control of defense
genes. We discuss how redox modifications of regulators and co-regulators
involved in SA-mediated transcriptional responses control the temporal patterns
of gene expression in response to stress. Finally, we examine how these redox
sensors are coordinated with the dynamics of cellular redox changes occurring in
the defense response to biotic and abiotic stress.
PMID- 25852722
TI - The male germline of angiosperms: repertoire of an inconspicuous but important
cell lineage.
AB - The male germline of flowering plants constitutes a specialized lineage of
diminutive cells initiated by an asymmetric division of the initial microspore
cell that sequesters the generative cell from the pollen vegetative cell. The
generative cell subsequently divides to form the two male gametes (non-motile
sperm cells) that fuse with the two female gametophyte target cells (egg and
central cells) to form the zygote and endosperm. Although these male gametes can
be as little as 1/800th of the volume of their female counterpart, they encode a
highly distinctive and rich transcriptome, translate proteins, and display a
novel suite of gamete-distinctive control elements that create a unique chromatin
environment in the male lineage. Sperm-expressed transcripts also include a high
proportion of transposable element-related sequences that may be targets of non
coding RNA including miRNA and silencing elements from peripheral cells. The
number of sperm-encoded transcripts is somewhat fewer than the number present in
the egg cell, but are remarkably distinct compared to other cell types according
to principal component and other analyses. The molecular role of the male germ
lineage cells is just beginning to be understood and appears more complex than
originally anticipated.
PMID- 25852724
TI - Analysis of genetic variation and diversity of Rice stripe virus populations
through high-throughput sequencing.
AB - Plant RNA viruses often generate diverse populations in their host plants through
error-prone replication and recombination. Recent studies on the genetic
diversity of plant RNA viruses in various host plants have provided valuable
information about RNA virus evolution and emergence of new diseases caused by RNA
viruses. We analyzed and compared the genetic diversity of Rice stripe virus
(RSV) populations in Oryza sativa (a natural host of RSV) and compared it with
that of the RSV populations generated in an infection of Nicotiana benthamiana,
an experimental host of RSV, using the high-throughput sequencing technology.
From infected O. sativa and N. benthamiana plants, a total of 341 and 1675 site
substitutions were identified in the RSV genome, respectively, and the average
substitution ratio in these sites was 1.47 and 7.05 %, respectively, indicating
that the RSV populations from infected N. benthamiana plant are more diverse than
those from infected O. sativa plant. Our result gives a direct evidence that
virus might allow higher genetic diversity for host adaptation.
PMID- 25852723
TI - Interconnection between flowering time control and activation of systemic
acquired resistance.
AB - The ability to avoid or neutralize pathogens is inherent to all higher organisms
including plants. Plants recognize pathogens through receptors, and mount
resistance against the intruders, with the help of well-elaborated defense
arsenal. In response to some localinfections, plants develop systemic acquired
resistance (SAR), which provides heightened resistance during subsequent
infections. Infected tissues generate mobile signaling molecules that travel to
the systemic tissues, where they epigenetically modify expression o a set of
genes to initiate the manifestation of SAR in distant tissues. Immune responses
are largely regulated at transcriptional level. Flowering is a developmental
transition that occurs as a result of the coordinated action of large numbers of
transcription factors that respond to intrinsic signals and environmental
conditions. The plant hormone salicylic acid (SA) which is required for SAR
activation positively regulates flowering. Certain components of chromatin
remodeling complexes that are recruited for suppression of precocious flowering
are also involved in suppression of SAR in healthy plants. FLOWERING LOCUS D, a
putative histone demethylase positively regulates SAR manifestation and flowering
transition in Arabidopsis. Similarly, incorporation of histone variant H2A.Z in
nucleosomes mediated by PHOTOPERIOD-INDEPENDENT EARLY FLOWERING 1, an ortholog of
yeast chromatin remodeling complex SWR1, concomitantly influences SAR and
flowering time. SUMO conjugation and deconjugation mechanisms also similarly
affect SAR and flowering in an SA-dependent manner. The evidences suggest a
common underlying regulatory mechanism for activation of SAR and flowering in
plants.
PMID- 25852725
TI - Lathyrus sativus transcriptome resistance response to Ascochyta lathyri
investigated by deepSuperSAGE analysis.
AB - Lathyrus sativus (grass pea) is a temperate grain legume crop with a great
potential for expansion in dry areas or zones that are becoming more drought
prone. It is also recognized as a potential source of resistance to several
important diseases in legumes, such as ascochyta blight. Nevertheless, the lack
of detailed genomic and/or transcriptomic information hampers further
exploitation of grass pea resistance-related genes in precision breeding. To
elucidate the pathways differentially regulated during ascochyta-grass pea
interaction and to identify resistance candidate genes, we compared the early
response of the leaf gene expression profile of a resistant L. sativus genotype
to Ascochyta lathyri infection with a non-inoculated control sample from the same
genotype employing deepSuperSAGE. This analysis generated 14.387 UniTags of which
95.7% mapped to a reference grass pea/rust interaction transcriptome. From the
total mapped UniTags, 738 were significantly differentially expressed between
control and inoculated leaves. The results indicate that several gene classes
acting in different phases of the plant/pathogen interaction are involved in the
L. sativus response to A. lathyri infection. Most notably a clear up-regulation
of defense-related genes involved in and/or regulated by the ethylene pathway was
observed. There was also evidence of alterations in cell wall metabolism
indicated by overexpression of cellulose synthase and lignin biosynthesis genes.
This first genome-wide overview of the gene expression profile of the L. sativus
response to ascochyta infection delivered a valuable set of candidate resistance
genes for future use in precision breeding.
PMID- 25852726
TI - The soybean GmDi19-5 interacts with GmLEA3.1 and increases sensitivity of
transgenic plants to abiotic stresses.
AB - Drought-induced (Di19) proteins played important roles in plant growth,
development, and abiotic stress responses. In the present study, a total of seven
Di19 genes were identified in soybean. Each soybean Di19 gene showed specific
responses to salt, drought, oxidative, and ABA stresses based on expression
profiles. With a relatively higher transcript level among Di19 members under four
stress treatments, GmDi19-5 was selected for detailed analysis. Inhibitor assays
revealed that ABA inhibitor (Fluridone) or H2O2 inhibitor (DMTU) was involved in
the drought- or salt-induced transcription of GmDi19-5. The GUS activity driven
by the GmDi19-5 promoter was induced by salt, PEG, ABA, and MV treatments and
tended to be accumulated in the vascular bundles and young leaves. A subcellular
localization assay showed that GmDi19-5 protein localized in the nucleus. Further
investigation showed that GmDi19-5 protein was involved in the interaction with
GmLEA3.1. Overexpression of GmDi19-5 increased sensitivity of transgenic
Arabidopsis plants to salt, drought, oxidative, and ABA stresses and regulated
expression of several ABA/stress-associated genes. This present investigation
showed that GmDi19-5 functioned as a negative factor under abiotic stresses and
was involved in ABA and SOS signaling pathway by altering transcription of stress
associated genes.
PMID- 25852727
TI - Fructan and hormone connections.
PMID- 25852728
TI - Copper-induced activation of TRP channels promotes extracellular calcium entry,
activation of CaMs and CDPKs, copper entry and membrane depolarization in Ulva
compressa.
AB - In order to identify channels involved in membrane depolarization, Ulva compressa
was incubated with agonists of TRP channels C5, A1 and V1, and the level of
intracellular calcium was detected. Agonists of TRPC5, A1 and V1 induced
increases in intracellular calcium at 4, 9, and 11 min of exposure, respectively,
and antagonists of TRPC5, A1, and V1 corresponding to SKF-96365 (SKF), HC-030031
(HC), and capsazepin (CPZ), respectively, inhibited calcium increases indicating
that functional TRPs exist in U. compressa. In addition, copper excess induced
increases in intracellular calcium at 4, 9, and 12 min which were inhibited by
SKF, HC, and CPZ, respectively, indicating that copper activate TRPC5, A1, and V1
channels. Moreover, copper-induced calcium increases were inhibited by EGTA, a
non-permeable calcium chelating agent, but not by thapsigargin, an inhibitor of
endoplasmic reticulum (ER) calcium ATPase, indicating that activation of TRPs
leads to extracellular calcium entry. Furthermore, copper-induced calcium
increases were not inhibited by W-7, an inhibitor of CaMs, and staurosporine, an
inhibitor of CDPKs, indicating that extracellular calcium entry did not require
activation of CaMs and CDPKs. In addition, copper induced membrane depolarization
events at 4, 8, and 11 min and these events were inhibited by SKF, HC, CPZ, and
bathocuproine, a specific copper chelating agent, indicating that copper entry
through TRP channels leads to membrane depolarization. Moreover, membrane
depolarization events were inhibited by W-7 and staurosporine, indicating that
activation of CaMs and CDPKs is required to allow copper entry through TRPs.
Interestingly, copper-induced calcium increases and depolarization events were
light-dependent and were inhibited by DCMU, an inhibitor of photosystem II, and
ATP-gamma-S, a non-hydrolizable analog of ATP, suggesting that ATP derived from
photosynthesis is required to activate TRPs. Thus, light-dependent copper-induced
activation TRPC5, A1 and V1 promotes extracellular calcium entry leading to
activation of CaMs and CDPKs which, in turn, promotes copper entry through TRP
channels and membrane depolarization.
PMID- 25852729
TI - MALDI-TOF MS profiling approach: how much can we get from it?
PMID- 25852730
TI - MicroRNA399 is involved in multiple nutrient starvation responses in rice.
AB - The increasing evidences have revealed that microRNAs (miRNAs) play significant
role in nutrient stress response. Previously, miR399 was documented to be induced
by phosphorus (P) starvation and involved in regulating P starvation responses.
To further investigate the function of miR399 in rice (Oryza sativa L.), we
performed GeneChip analysis with OsmiR399 over-expressing plants. Interestingly,
our results showed that, besides P starvation responsive genes, the expression of
a number of genes involved in iron (Fe), potassium (K), sodium (Na), and calcium
(Ca) absorption was dramatically up-regulated in OsmiR399 over-expressing plants.
Consistently, the concentrations of Fe, K, Na, and Ca were also increased in
OsmiR399 over-expressing plants. The expression of OsmiR399 was also up-regulated
by these nutrient starvations, respectively. Moreover, the loss-of-function of
LTN1, the down-stream target of OsmiR399, also resulted in the increase of
multiple metal elements and the up-regulation of the absorption related genes.
These results indicated that OsmiR399 participates in the regulation of multiple
nutrient starvation responses, which also gives new view on understanding the
interaction among different nutrients mediated by miR399.
PMID- 25852731
TI - Anosognosia in people with cognitive impairment: association with cognitive
deficits and behavioral disturbances.
AB - AIMS: To investigate, in a group of subjects at an early stage of cognitive
impairment, the relationship between anosognosia and both cognitive and
behavioral symptoms by exploring the various domains of insight. METHODS: One
hundred and eight subjects affected by cognitive impairment were consecutively
enrolled. The level of awareness was evaluated by means of the Clinical Insight
Rating Scale (CIRS). Psychiatric symptoms were evaluated using the Italian
version of the Neuropsychiatric Inventory (NPI), whereas memory (memory index,
MI) and executive (executive index, EI) functions were explored using a battery
of neuropsychological tests and qualified by means of a single composite
cognitive index score for each function. RESULTS: A significant positive
correlation between the total NPI score and global anosognosia score was found.
Furthermore, both the MI and EI scores were lower in subjects with anosognosia
than in those without anosognosia (p < 0.001 and p < 0.007, respectively). When
the single domains of the CIRS were considered, anosognosia of reason of visit
correlated with the EI score (r = -0.327, p = 0.01) and night-time behavioral
disturbances (r = 0.225; p = 0.021); anosognosia of cognitive deficit correlated
with depression (r = -0.193; p = 0.049) and the MI score (r = -0.201; p = 0.040);
anosognosia of functional deficit correlated with the MI score (r = -0.257; p =
0.008), delusions (r = 0.232; p = 0.015) and aberrant motor behavior (r = 0.289;
p = 0.003); anosognosia of disease progression correlated with the MI score (r =
0.236; p = 0.015), agitation (r = 0.247; p = 0.011), aberrant motor behavior (r =
0.351; p = 0.001) and night-time behavioral disturbances (r = 0.216; p = 0.027).
CONCLUSIONS: Our study suggests that, in the early stage of cognitive impairment,
anosognosia is associated with both cognitive deficits and behavioral disorders
according to the specific functional anatomy of the symptoms.
PMID- 25852732
TI - Effects of pioglitazone or exercise in older adults with mild cognitive
impairment and insulin resistance: a pilot study.
AB - AIMS: To examine the effects of pioglitazone or endurance exercise training on
cognitive function in older adults with mild cognitive impairment (MCI) and
insulin resistance. METHODS: Seventy-eight adults (mean age +/- SD: 65 +/- 7
years) with central obesity and MCI were randomized to 6 months of endurance
exercise, pioglitazone or control. RESULTS: Sixty-six participants completed the
study. Exercise training did not significantly increase peak oxygen uptake
compared to control (p = 0.12). Compared to control, insulin resistance improved
in the pioglitazone group (p = 0.002) but not in the exercise group (p = 0.25).
There was no measureable effect of pioglitazone or exercise on cognitive
performance compared to control. CONCLUSION: In this pilot study, pioglitazone
improved insulin resistance but not cognitive performance in older adults with
MCI and insulin resistance.
PMID- 25852734
TI - Lipid levels and renal function decline in pre-dialysis patients.
AB - BACKGROUND: Little is known about the effect of low-density lipoprotein (LDL)
cholesterol, triglyceride (TG), and high-density lipoprotein (HDL) cholesterol
levels on renal function decline in patients receiving specialized pre-dialysis
care. METHODS: In the prospective PREPARE-2 study, incident patients starting pre
dialysis care were included when referred to one of the 25 participating Dutch
specialized pre-dialysis outpatient clinics (2004-2011). Clinical and laboratory
data were collected every 6 months. A linear mixed model was used to compare
renal function decline between patients with LDL cholesterol, TG, or HDL
cholesterol levels above and below the target goals (LDL cholesterol: <2.50
mmol/l, TG: <2.25 mmol/l, and HDL cholesterol: >=1.00 mmol/l). Additionally the
HDL/LDL cholesterol ratio was investigated (>=0.4). RESULTS: In our study
population (n = 306), the median age was 69 years and 70% were male. Patients
with LDL cholesterol levels above the target of 2.50 mmol/l experienced an
accelerated renal function decline compared to patients with levels below the
target (crude additional decline: 0.10 ml/min/1.73 m(2)/month, 95% CI 0.00-0.20;
p < 0.05). A similar trend was found for TG levels above the target of 2.25
mmol/l (0.05 ml/min/1.73 m(2)/month, 95% CI -0.06 to 0.16) and for a HDL/LDL
cholesterol ratio below 0.4 (0.06 ml/min/1.73 m(2)/month, 95% CI -0.05 to 0.18).
Adjustment for potential confounders resulted in similar results, and the
exclusion of patients who were prescribed lipid-lowering medication (statin,
fibrate, or cholesterol absorption inhibitor) resulted in a slightly larger
estimated effect. CONCLUSION: High levels of LDL cholesterol were associated with
an accelerated renal function decline, independent of the prescription of lipid
lowering medication.
PMID- 25852733
TI - Effects of Tumor Necrosis Factor-alpha on Podocyte Expression of Monocyte
Chemoattractant Protein-1 and in Diabetic Nephropathy.
AB - BACKGROUND/AIMS: Tumor necrosis factor (TNF)-alpha is believed to play a role in
diabetic kidney disease. This study explores the specific effects of TNF-alpha
with regard to nephropathy-relevant parameters in the podocyte. METHODS: Cultured
mouse podocytes were treated with recombinant TNF-alpha and assayed for
production of monocyte chemoattractant protein-1 (MCP-1) by enzyme-linked
immunosorbent assay (ELISA). TNF-alpha signaling of MCP-1 was elucidated by
antibodies against TNF receptor (TNFR) 1 or TNFR2 or inhibitors of nuclear factor
kappaB (NF-kappaB), phosphatidylinositol 3-kinase (PI3K) or Akt. In vivo studies
were done on male db/m and type 2 diabetic db/db mice. Levels of TNF-alpha and
MCP-1 were measured by RT-qPCR and ELISA in the urine, kidney and plasma of the
two cohorts and correlated with albuminuria. RESULTS: Podocytes treated with TNF
alpha showed a robust increase (~900%) in the secretion of MCP-1, induced in a
dose- and time-dependent manner. Signaling of MCP-1 expression occurred through
TNFR2, which was inducible by TNF-alpha ligand, but did not depend on TNFR1. TNF
alpha then proceeded via the NF-kappaB and the PI3K/Akt systems, based on the
effectiveness of the inhibitors of those pathways. For in vivo relevance to
diabetic kidney disease, TNF-alpha and MCP-1 levels were found to be elevated in
the urine of db/db mice but not in the plasma. CONCLUSION: TNF-alpha potently
stimulates podocytes to produce MCP-1, utilizing the TNFR2 receptor and the NF
kappaB and PI3K/Akt pathways. Both TNF-alpha and MCP-1 levels were increased in
the urine of diabetic db/db mice, correlating with the severity of diabetic
albuminuria.
PMID- 25852735
TI - Mapping the global mRNA transcriptome during development of the murine first
molar.
AB - The main objective of this study was to map global gene expression in order to
provide information about the populations of mRNA species participating in murine
tooth development at 24 h intervals, starting at the 11th embryonic day (E11.5)
up to the 7th post-natal day (P7). The levels of RNA species expressed during
murine tooth development were mesured using a total of 58 deoxyoligonucleotide
microarrays. Microarray data was validated using real-time RT-PCR. Differentially
expressed genes (p < 0.05) were subjected to bioinformatic analysis to identify
cellular activities significantly associated with these genes. Using ANOVA the
microarray data yielded 4362 genes as being differentially expressed from the
11th embryonic day (E11.5) up to 7 days post-natal (P7), 1921 of these being
genes without known functions. The remaining 2441 genes were subjected to further
statistical analysis using a supervised procedure. Bioinformatic analysis results
for each time-point studied suggests that the main molecular functions associated
with genes expressed at the early pre-natal stages (E12.5-E18.5) were cell cycle
progression, cell morphology, lipid metabolism, cellular growth, proliferation,
senescence and apoptosis, whereas most genes expressed at post-natal and
secretory stages (P0-P7) were significantly associated with regulation of cell
migration, biosynthesis, differentiation, oxidative stress, polarization and cell
death. Differentially expressed genes (DE) not described earlier during murine
tooth development; Inositol 1, 4, 5-triphosphate receptor 3 (Itpr3),
metallothionein 1(Mt1), cyclin-dependent kinase 4 (Cdk4), cathepsin D (Ctsd),
keratin complex 2, basic, gene 6a (Krt2-6a), cofilin 1, non-muscle (Cfl1), cyclin
2 (Ccnd2), were verified by real-time RT-PCR.
PMID- 25852736
TI - Integrated genomic and BMI analysis for type 2 diabetes risk assessment.
AB - Type 2 Diabetes (T2D) is a chronic disease arising from the development of
insulin absence or resistance within the body, and a complex interplay of
environmental and genetic factors. The incidence of T2D has increased throughout
the last few decades, together with the occurrence of the obesity epidemic. The
consideration of variants identified by Genome Wide Association Studies (GWAS)
into risk assessment models for T2D could aid in the identification of at-risk
patients who could benefit from preventive medicine. In this study, we build
several risk assessment models, evaluated with two different classification
approaches (Logistic Regression and Neural Networks), to measure the effect of
including genetic information in the prediction of T2D. We used data from to the
Original and the Offspring cohorts of the Framingham Heart Study, which provides
phenotypic and genetic information for 5245 subjects (4306 controls and 939
cases). Models were built by using several covariates: gender, exposure time,
cohort, body mass index (BMI), and 65 SNPs associated to T2D. We fitted Logistic
Regressions and Bayesian Regularized Neural Networks and then assessed their
predictive ability by using a ten-fold cross validation. We found that the
inclusion of genetic information into the risk assessment models increased the
predictive ability by 2%, when compared to the baseline model. Furthermore, the
models that included BMI at the onset of diabetes as a possible effector, gave an
improvement of 6% in the area under the curve derived from the ROC analysis. The
highest AUC achieved (0.75) belonged to the model that included BMI, and a
genetic score based on the 65 established T2D-associated SNPs. Finally, the
inclusion of SNPs and BMI raised predictive ability in all models as expected;
however, results from the AUC in Neural Networks and Logistic Regression did not
differ significantly in their prediction accuracy.
PMID- 25852738
TI - Telomeric aging: mitotic clock or stress indicator?
PMID- 25852737
TI - Mucin glycan foraging in the human gut microbiome.
AB - The availability of host and dietary carbohydrates in the gastrointestinal (GI)
tract plays a key role in shaping the structure-function of the microbiota. In
particular, some gut bacteria have the ability to forage on glycans provided by
the mucus layer covering the GI tract. The O-glycan structures present in mucin
are diverse and complex, consisting predominantly of core 1-4 mucin-type O
glycans containing alpha- and beta- linked N-acetyl-galactosamine, galactose and
N-acetyl-glucosamine. These core structures are further elongated and frequently
modified by fucose and sialic acid sugar residues via alpha1,2/3/4 and alpha2,3/6
linkages, respectively. The ability to metabolize these mucin O-linked
oligosaccharides is likely to be a key factor in determining which bacterial
species colonize the mucosal surface. Due to their proximity to the immune
system, mucin-degrading bacteria are in a prime location to influence the host
response. However, despite the growing number of bacterial genome sequences
available from mucin degraders, our knowledge on the structural requirements for
mucin degradation by gut bacteria remains fragmented. This is largely due to the
limited number of functionally characterized enzymes and the lack of studies
correlating the specificity of these enzymes with the ability of the strain to
degrade and utilize mucin and mucin glycans. This review focuses on recent
findings unraveling the molecular strategies used by mucin-degrading bacteria to
utilize host glycans, adapt to the mucosal environment, and influence human
health.
PMID- 25852740
TI - Genetic improvement of Pacific white shrimp [Penaeus (Litopenaeus) vannamei]:
perspectives for genomic selection.
AB - The uses of breeding programs for the Pacific white shrimp [Penaeus (Litopenaeus)
vannamei] based on mixed linear models with pedigreed data are described. The
application of these classic breeding methods yielded continuous progress of
great value to increase the profitability of the shrimp industry in several
countries. Recent advances in such areas as genomics in shrimp will allow for the
development of new breeding programs in the near future that will increase
genetic progress. In particular, these novel techniques may help increase disease
resistance to specific emerging diseases, which is today a very important
component of shrimp breeding programs. Thanks to increased selection accuracy,
simulated genetic advance using genomic selection for survival to a disease
challenge was up to 2.6 times that of phenotypic sib selection.
PMID- 25852739
TI - On the road with WRAP53beta: guardian of Cajal bodies and genome integrity.
AB - The WRAP53 gene encodes both an antisense transcript (WRAP53alpha) that
stabilizes the tumor suppressor p53 and a protein (WRAP53beta) involved in
maintenance of Cajal bodies, telomere elongation and DNA repair. WRAP53beta is
one of many proteins containing WD40 domains, known to mediate a variety of
cellular processes. These proteins lack enzymatic activity, acting instead as
platforms for the assembly of large complexes of proteins and RNAs thus
facilitating their interactions. WRAP53beta mediates site-specific interactions
between Cajal body factors and DNA repair proteins. Moreover, dysfunction of this
protein has been linked to premature aging, cancer and neurodegeneration. Here we
summarize the current state of knowledge concerning the multifaceted roles of
WRAP53beta in intracellular trafficking, formation of the Cajal body, DNA repair
and maintenance of genomic integrity and discuss potential crosstalk between
these processes.
PMID- 25852741
TI - Nuclear envelope and genome interactions in cell fate.
AB - The eukaryotic cell nucleus houses an organism's genome and is the location
within the cell where all signaling induced and development-driven gene
expression programs are ultimately specified. The genome is enclosed and
separated from the cytoplasm by the nuclear envelope (NE), a double-lipid
membrane bilayer, which contains a large variety of trans-membrane and associated
protein complexes. In recent years, research regarding multiple aspects of the
cell nucleus points to a highly dynamic and coordinated concert of efforts
between chromatin and the NE in regulation of gene expression. Details of how
this concert is orchestrated and how it directs cell differentiation and disease
are coming to light at a rapid pace. Here we review existing and emerging
concepts of how interactions between the genome and the NE may contribute to
tissue specific gene expression programs to determine cell fate.
PMID- 25852743
TI - Metatranscriptomic analyses of honey bee colonies.
AB - Honey bees face numerous biotic threats from viruses to bacteria, fungi,
protists, and mites. Here we describe a thorough analysis of microbes harbored by
worker honey bees collected from field colonies in geographically distinct
regions of Turkey. Turkey is one of the World's most important centers of
apiculture, harboring five subspecies of Apis mellifera L., approximately 20% of
the honey bee subspecies in the world. We use deep ILLUMINA-based RNA sequencing
to capture RNA species for the honey bee and a sampling of all non-endogenous
species carried by bees. After trimming and mapping these reads to the honey bee
genome, approximately 10% of the sequences (9-10 million reads per library)
remained. These were then mapped to a curated set of public sequences containing
ca. Sixty megabase-pairs of sequence representing known microbial species
associated with honey bees. Levels of key honey bee pathogens were confirmed
using quantitative PCR screens. We contrast microbial matches across different
sites in Turkey, showing new country recordings of Lake Sinai virus, two
Spiroplasma bacterium species, symbionts Candidatus Schmidhempelia bombi,
Frischella perrara, Snodgrassella alvi, Gilliamella apicola, Lactobacillus spp.),
neogregarines, and a trypanosome species. By using metagenomic analysis, this
study also reveals deep molecular evidence for the presence of bacterial
pathogens (Melissococcus plutonius, Paenibacillus larvae), Varroa destructor-1
virus, Sacbrood virus, and fungi. Despite this effort we did not detect KBV,
SBPV, Tobacco ringspot virus, VdMLV (Varroa Macula like virus), Acarapis spp.,
Tropilaeleps spp. and Apocephalus (phorid fly). We discuss possible impacts of
management practices and honey bee subspecies on microbial retinues. The
described workflow and curated microbial database will be generally useful for
microbial surveys of healthy and declining honey bees.
PMID- 25852742
TI - Regulators of homologous recombination repair as novel targets for cancer
treatment.
AB - To cope with DNA damage, cells possess a complex signaling network called the
'DNA damage response', which coordinates cell cycle control with DNA repair. The
importance of this network is underscored by the cancer predisposition that
frequently goes along with hereditary mutations in DNA repair genes. One
especially important DNA repair pathway in this respect is homologous
recombination (HR) repair. Defects in HR repair are observed in various cancers,
including hereditary breast, and ovarian cancer. Intriguingly, tumor cells with
defective HR repair show increased sensitivity to chemotherapeutic reagents,
including platinum-containing agents. These observations suggest that HR
proficient tumor cells might be sensitized to chemotherapeutics if HR repair
could be therapeutically inactivated. HR repair is an extensively regulated
process, which depends strongly on the activity of various other pathways,
including cell cycle pathways, protein-control pathways, and growth factor
activated receptor signaling pathways. In this review, we discuss how the
mechanistic wiring of HR is controlled by cell-intrinsic or extracellular
pathways. Furthermore, we have performed a meta-analysis on available genome-wide
RNA interference studies to identify additional pathways that control HR repair.
Finally, we discuss how these HR-regulatory pathways may provide therapeutic
targets in the context of radio/chemosensitization.
PMID- 25852744
TI - Long-term survival in a child with severe encephalopathy, multiple respiratory
chain deficiency and GFM1 mutations.
AB - BACKGROUND: Mitochondrial diseases due to deficiencies in the mitochondrial
oxidative phosphorylation system (OXPHOS) can be associated with nuclear genes
involved in mitochondrial translation, causing heterogeneous early onset and
often fatal phenotypes. CASE REPORT: The authors describe the clinical features
and diagnostic workup of an infant who presented with an early onset severe
encephalopathy, spastic-dystonic tetraparesis, failure to thrive, seizures and
persistent lactic acidemia. Brain imaging revealed thinning of the corpus
callosum and diffuse alteration of white matter signal. Genetic investigation
confirmed two novel mutations in the GFM1 gene, encoding the mitochondrial
translation elongation factor G1 (mtEFG1), resulting in combined deficiencies of
OXPHOS. DISCUSSION: The patient shares multiple clinical, laboratory and
radiological similarities with the 11 reported patients with mutations involving
this gene, but presents with a stable clinical course without metabolic
decompensations, rather than a rapidly progressive fatal course. Defects in GFM1
gene confer high susceptibility to neurologic or hepatic dysfunction and this is,
to the best of our knowledge, the first described patient who has survived beyond
early childhood. Reporting of such cases is essential so as to delineate the key
clinical and neuroradiological features of this disease and provide a more
comprehensive view of its prognosis.
PMID- 25852745
TI - The foundation of precision medicine: integration of electronic health records
with genomics through basic, clinical, and translational research.
PMID- 25852746
TI - Fecal egg counts for gastrointestinal nematodes are associated with a
polymorphism in the MHC-DRB1 gene in the Iranian Ghezel sheep breed.
AB - Genetic variation among sheep breeds in resistance to gastrointestinal nematodes
(GIN) has been demonstrated in several production environments. Relationships
between the ovine major histocompatibility complex and resistance to GIN have
been studied, but few studies have systematically examined this issue in less
developed and semi-arid regions. The aim of the current study was to explore
associations between fecal worm egg counts (FEC) for several GIN and
polymorphisms in the DRB1 gene. One hundred male lambs were selected at 4-6
months of age from weaned animals in five flocks (n = 20 per flock). Body weights
were determined, FAMACHA scores based on color of the ocular mucous membranes
were assigned as an indicator of anemia, and blood and fecal samples were
collected twice to evaluate FEC and blood packed cell volume (PCV) and for DNA
isolation. A repeated-measures analysis of variance was used to test effects of
genotype on FEC. The model included fixed effects of flock, genotype, time of
measurement (1 or 2), and flock * time and genoype * time interactions, and a
random (repeated) effect of lamb. Two genotypes (A1A1 and A1A2) were observed
following digestion of Region 1 of Ovar-DRB1 with PstI. Genotypic frequencies
were 0.73 for A1A1 and 0.27 for A1A2. FEC differed between Ovar_DRB1 genotypes
A1A1 and A1A2 for Marshallagia marshalli, Strongyle, and total nematode FEC.
Observed FEC were 30-41% lower for genotype A1A1. Differences among genotypes
were consistent across measurement times, with no effect of genotype *
measurement time interaction for any parasite class (P >= 0.34). A significant
association was observed between FAMACHA scores and lamb PCV, and the residual
correlation between these two variables was -0.51 (P < 0.001). FAMACHA scores can
thus be used to detect differences among lambs in PCV, and polymorphic markers of
Ovar-DRB1 have potential value as an indicator of parasite resistance in applied
animal breeding programs on sheep farms in this region.
PMID- 25852748
TI - SNeP: a tool to estimate trends in recent effective population size trajectories
using genome-wide SNP data.
AB - Effective population size (Ne ) is a key population genetic parameter that
describes the amount of genetic drift in a population. Estimating Ne has been
subject to much research over the last 80 years. Methods to estimate Ne from
linkage disequilibrium (LD) were developed ~40 years ago but depend on the
availability of large amounts of genetic marker data that only the most recent
advances in DNA technology have made available. Here we introduce SNeP, a
multithreaded tool to perform the estimate of Ne using LD using the standard
PLINK input file format (.ped and.map files) or by using LD values calculated
using other software. Through SNeP the user can apply several corrections to take
account of sample size, mutation, phasing, and recombination rate. Each variable
involved in the computation such as the binning parameters or the chromosomes to
include in the analysis can be modified. When applied to published datasets, SNeP
produced results closely comparable with those obtained in the original studies.
The use of SNeP to estimate Ne trends can improve understanding of population
demography in the recent past, provided a sufficient number of SNPs and their
physical position in the genome are available. Binaries for the most common
operating systems are available at
https://sourceforge.net/projects/snepnetrends/.
PMID- 25852747
TI - DNA polymerase gamma and disease: what we have learned from yeast.
AB - Mip1 is the Saccharomyces cerevisiae DNA polymerase gamma (Pol gamma), which is
responsible for the replication of mitochondrial DNA (mtDNA). It belongs to the
family A of the DNA polymerases and it is orthologs to human POLGA. In humans,
mutations in POLG(1) cause many mitochondrial pathologies, such as progressive
external ophthalmoplegia (PEO), Alpers' syndrome, and ataxia-neuropathy syndrome,
all of which present instability of mtDNA, which results in impaired
mitochondrial function in several tissues with variable degrees of severity. In
this review, we summarize the genetic and biochemical knowledge published on
yeast mitochondrial DNA polymerase from 1989, when the MIP1 gene was first
cloned, up until now. The role of yeast is particularly emphasized in (i)
validating the pathological mutations found in human POLG and modeled in MIP1,
(ii) determining the molecular defects caused by these mutations and (iii)
finding the correlation between mutations/polymorphisms in POLGA and mtDNA
toxicity induced by specific drugs. We also describe recent findings regarding
the discovery of molecules able to rescue the phenotypic defects caused by
pathological mutations in Mip1, and the construction of a model system in which
the human Pol gamma holoenzyme is expressed in yeast and complements the loss of
Mip1.
PMID- 25852749
TI - Mutations of mitochondrial genome in carotid atherosclerosis.
AB - With aim of detection the spectrum of mitochondrial DNA mutations in patients
with carotid atherosclerosis from Moscow Region, we used a Roche 454 high
throughput sequencing of the whole mitochondrial genome. We have found that the
presence of a number of homoplasmic mitochondrial DNA mutations in genes of 16S
ribosomal RNA, subunits 2, 4, and 5 NADH dehydrogenase, subunits 1 and 2
cytochrome C oxidase, subunit 6 ATP-synthase, tRNA- Leu 2 and cytochrome B
differed between conventionally healthy participants of the study and patients
with carotid atherosclerosis. We also found heteroplasmic mutations, including
insertions one or several nucleotides, that occurred more frequently in
mitochondrial DNA of conventionally healthy participants of the study or patients
with atherosclerotic lesions.
PMID- 25852750
TI - The phenotypic expression of mitochondrial tRNA-mutations can be modulated by
either mitochondrial leucyl-tRNA synthetase or the C-terminal domain thereof.
AB - Mutations in mitochondrial (mt) DNA determine important human diseases. The
majority of the known pathogenic mutations are located in transfer RNA (tRNA)
genes and are responsible for a wide range of currently untreatable disorders.
Experimental evidence both in yeast and in human cells has shown that the
detrimental effects of mt-tRNA point mutations can be attenuated by increasing
the expression of the cognate mt-aminoacyl-tRNA synthetases (aaRSs). In addition,
constitutive high levels of isoleucyl-tRNA syntethase have been shown to reduce
the penetrance of a homoplasmic mutation in mt-tRNA(Ile) in a small kindred. More
recently, we showed that the isolated carboxy-terminal domain of human mt-leucyl
tRNA synthetase (LeuRS-Cterm) localizes to mitochondria and ameliorates the
energetic defect in transmitochondrial cybrids carrying mutations either in the
cognate mt-tRNA(Leu(UUR)) or in the non-cognate mt-tRNA(Ile) gene. Since the mt
LeuRS-Cterm does not possess catalytic activity, its rescuing ability is most
likely mediated by a chaperon-like effect, consisting in the stabilization of the
tRNA structure altered by the mutation. All together, these observations open
potential therapeutic options for mt-tRNA mutations-associated diseases.
PMID- 25852753
TI - A comparison of two invagination techniques for pancreatojejunostomy after
pancreatoduodenectomy.
AB - Background. The aim of the study was to compare two invagination techniques for
pancreatojejunostomy after pancreatoduodenectomy. Methods. For effective
prevention of the development of pancreatic leakage, we modified invagination
technique that we term the "serous touch." We analysed the diameter of the main
pancreatic duct, the texture of the remnant pancreas, the method of the
reconstruction, pancreatic external drainage, anastomotic procedure time,
histopathological examination, and postoperative complications. Results. Fifty
two patients underwent pancreatoduodenectomy with pancreatojejunostomy using
"serous touch" technique (ST group) and 52 classic pancreatojejunostomy (C
group). In the ST group one patient (1.9%) was diagnosed as grade B pancreatic
fistula, and no patient experienced fistula grade A or C. In the C group 6
patients (11.5%) were diagnosed as fistula grade A, 1 (1.9%) patient as fistula
grade B, and 1 (1.9%) patient as fistula grade C. There was a significant
statistical difference in incidents of pancreatic fistula (P < 0.05) and no
statistical difference in other postoperative complications or mortality in
comparison group. Anastomosis time was statistically shorter in the ST group.
Conclusions. "Serous touch" technique appeared to be easy, safe, associated with
fewer incidences of pancreatic fistulas, and less time consuming in comparison
with classical pancreatojejunostomy.
PMID- 25852751
TI - Mononuclear cells and vascular repair in HHT.
AB - Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a
rare genetic vascular disorder known for its endothelial dysplasia causing
arteriovenous malformations and severe bleedings. HHT-1 and HHT-2 are the most
prevalent variants and are caused by heterozygous mutations in endoglin and
activin receptor-like kinase 1, respectively. An undervalued aspect of the
disease is that HHT patients experience persistent inflammation. Although
endothelial and mural cells have been the main research focus trying to unravel
the mechanism behind the disease, wound healing is a process with a delicate
balance between inflammatory and vascular cells. Inflammatory cells are part of
the mononuclear cells (MNCs) fraction, and can, next to eliciting an immune
response, also have angiogenic potential. This biphasic effect of MNC can hold a
promising mechanism to further elucidate treatment strategies for HHT patients.
Before MNC are able to contribute to repair, they need to home to and retain in
ischemic and damaged tissue. Directed migration (homing) of MNCs following tissue
damage is regulated by the stromal cell derived factor 1 (SDF1). MNCs that
express the C-X-C chemokine receptor 4 (CXCR4) migrate toward the tightly
regulated gradient of SDF1. This directed migration of monocytes and lymphocytes
can be inhibited by dipeptidyl peptidase 4 (DPP4). Interestingly, MNC of HHT
patients express elevated levels of DPP4 and show impaired homing toward damaged
tissue. Impaired homing capacity of the MNCs might therefore contribute to the
impaired angiogenesis and tissue repair observed in HHT patients. This review
summarizes recent studies regarding the role of MNCs in the etiology of HHT and
vascular repair, and evaluates the efficacy of DPP4 inhibition in tissue
integrity and repair.
PMID- 25852754
TI - Ebola virus disease 2013-2014 outbreak in west Africa: an analysis of the
epidemic spread and response.
AB - The Ebola virus epidemic burst in West Africa in late 2013, started in Guinea,
reached in a few months an alarming diffusion, actually involving several
countries (Liberia, Sierra Leone, Nigeria, Senegal, and Mali). Guinea and
Liberia, the first nations affected by the outbreak, have put in place measures
to contain the spread, supported by international organizations; then they were
followed by the other nations affected. In the present EVD outbreak, the
geographical spread of the virus has followed a new route: the achievement of
large urban areas at an early stage of the epidemic has led to an unprecedented
diffusion, featuring the largest outbreak of EVD of all time. This has caused
significant concerns all over the world: the potential reaching of far countries
from endemic areas, mainly through fast transports, induced several countries to
issue information documents and health supervision for individuals going to or
coming from the areas at risk. In this paper the geographical spread of the
epidemic was analyzed, assessing the sequential appearance of cases by geographic
area, considering the increase in cases and mortality according to affected
nations. The measures implemented by each government and international
organizations to contain the outbreak, and their effectiveness, were also
evaluated.
PMID- 25852752
TI - Drosophila melanogaster Hsp22: a mitochondrial small heat shock protein
influencing the aging process.
AB - Mitochondria are involved in many key cellular processes and therefore need to
rely on good protein quality control (PQC). Three types of mechanisms are in
place to insure mitochondrial protein integrity: reactive oxygen species
scavenging by anti-oxidant enzymes, protein folding/degradation by molecular
chaperones and proteases and clearance of defective mitochondria by mitophagy.
Drosophila melanogaster Hsp22 is part of the molecular chaperone axis of the PQC
and is characterized by its intra-mitochondrial localization and preferential
expression during aging. As a stress biomarker, the level of its expression
during aging has been shown to partially predict the remaining lifespan of flies.
Since over-expression of this small heat shock protein increases lifespan and
resistance to stress, Hsp22 most likely has a positive effect on mitochondrial
integrity. Accordingly, Hsp22 has recently been implicated in the mitochondrial
unfolding protein response of flies. This review will summarize the key findings
on D. melanogaster Hsp22 and emphasis on its links with the aging process.
PMID- 25852755
TI - Beneficial effects of coculturing synovial derived mesenchymal stem cells with
meniscus fibrochondrocytes are mediated by fibroblast growth factor 1: increased
proliferation and collagen synthesis.
AB - Meniscus reconstruction is in great need for orthopedic surgeons. Meniscal
fibrochondrocytes transplantation was proposed to regenerate functional meniscus,
with limited donor supply. We hypothesized that coculture of synovial mesenchymal
stem cells (SSC) with meniscal fibrochondrocytes (me-CH) can support matrix
production of me-CH, thus reducing the number of me-CH needed for meniscus
reconstruction. A pellet coculture system of human SSC and me-CH was used in this
study. Enhanced glycosaminoglycans (GAG) in coculture pellets were demonstrated
by Alcian blue staining and GAG quantification, when compared to monoculture.
More collagen synthesis was shown in coculture pellets by hydroxyproline assay.
Increased proliferation of me-CH was observed in coculture. Data from BrdU
staining and ELISA demonstrated that conditioned medium of SSCs enhanced the
proliferation and collagen synthesis of me-CH, and this effect was blocked by
neutralizing antibody against fibroblast growth factor 1 (FGF1). Western blot
showed that conditioned medium of SSCs can activate mitogen-activated protein
kinase (MAPK) signaling pathways by increasing the phosphorylation of mitogen
activated regulated protein kinase 1/2 (MEK) and extracellular-signal-regulated
kinases 1/2 (ERK). Overall, this study provided evidence that synovial MSCs can
support proliferation and collagen synthesis of fibrochondrocytes, by secreting
FGF1. Coimplantation of SSC and me-CH could be a useful strategy for
reconstructing meniscus.
PMID- 25852756
TI - Anthracosis of the lungs: etiology, clinical manifestations and diagnosis: a
review.
AB - Anthracosis of the lungs is black discoloration of bronchial mucosa that can
occlude bronchial lumen and is associated with bronchial anthracofibrosis (BAF).
This disease usually presents with a chronic course of dyspnea and or cough in an
elderly non-smoker woman or man. In addition, concomitant exposure to dust and
wood smoke is the most postulated etiology for anthracosis. Pulmonary function
tests usually show an obstructive pattern with no response to bronchodilators and
normal DLCO, but some cases with restrictive pattern have also been seen.
Computed tomography (CT) may show more specific findings such as lymph node or
bronchial calcification and mass lesions. Final diagnosis can be made by
bronchoscopy when obtaining samples for tuberculosis (TB), which is the most
common disease associated with BAF. Endobronchial ultrasound shows a hypoechoic
scattered nodular pattern in adjacent lymph nodes, which is unique to
anthracosis. Treatment is very similar to that of chronic obstructive pulmonary
disease (COPD) with a chronic course and low mortality. This review discusses
this disease as a separate entity; hence, anthracosis should be added to the list
of obstructive lung diseases and benign mass lesions and differentiated from
biomass induced COPD.
PMID- 25852757
TI - Clinical and radiographic manifestations and treatment outcome of pulmonary
tuberculosis in the elderly in khuzestan, southwest iran.
AB - BACKGROUND: Presentation of pulmonary tuberculosis (PTB) in the elderly is
expected to be different from that in younger patients because of the
debilitating factors and comorbidities. This issue should be considered in the
national tuberculosis programs of countries. The purpose of this study was to
evaluate the differences in the clinical and radiographic manifestations and
treatment outcomes of PTB between the elderly and young patients. MATERIALS AND
METHODS: This study was conducted as part of a mega project on tuberculosis by
the Infectious and Tropical Diseases Research Centre affiliated to Ahvaz
Jundishapur University of Medical Sciences. We retrospectively analyzed the
medical records of 2,080 relatively young (18-64 years old at the time of
diagnosis) and 346 elderly (>=65 years) PTB patients, who had been recently
diagnosed and treated in the TB unit of Khuzestan Health Center from 2005 to
2010. RESULTS: Dyspnea and hemoptysis were the most common symptoms and the
frequency of positive sputum smear -AFB was lower in the elderly PTB patients. On
chest X-ray, elderly patients were less likely to have cavitation in comparison
with younger patients. The frequency of favourable treatment outcome in the
elderly was significantly lower than that in younger patients (64% vs. 77%, P =
0.003). CONCLUSION: Dyspnea, weight loss and hemoptysis were more common in the
elderly PTB patients. Chest X-ray showed less frequent typical findings of active
PTB such as cavitation; and microscopic examination showed fewer sputum smear AFB
positive cases in the elderly. The treatment outcome was less favorable in the
elderly compared to younger TB patients.
PMID- 25852758
TI - Predictors of non-invasive ventilation failure in severe respiratory failure due
to community acquired pneumonia.
AB - BACKGROUND: Non-invasive ventilation (NIV) has been used for acute respiratory
failure to avoid endotracheal intubation and intensive care admission. Few
studies have assessed the usefulness of NIV in patients with severe community
acquired pneumonia (CAP). The use of NIV in severe CAP is controversial because
there is a greater variability in success compared to other pulmonary conditions.
MATERIALS AND METHODS: We retrospectively followed 130 patients with CAP and
severe acute respiratory failure (PaO2/FiO2 < 250) admitted to a Respiratory
Monitoring Unit (RMU) and underwent NIV. We assessed predictors of NIV failure
and hospital mortality using univariate and multivariate analyses. RESULTS: NIV
failed in 26 patients (20.0%). Higher chest X-ray score at admission, higher
heart rate after 1 hour of NIV, and a higher alveolar-arteriolar gradient (A
aDO2) after 24 hours of NIV each independently predicted NIV failure. Higher
chest X ray score, higher LDH at admission, higher heart rate after 24 hours of
NIV and higher A-aDO2 after 24 hours of NIV were directly related to hospital
mortality. CONCLUSION: NIV treatment had high rate of success. Successful
treatment is related to less lung involvement and to early good response to NIV
and continuous improvement in clinical response.
PMID- 25852760
TI - Qualification study of two genomic DNA extraction methods in different clinical
samples.
AB - INTRODUCTION: The purity of genomic DNA (gDNA) extracted from different clinical
specimens optimizes sensitivity of polymerase chain reaction (PCR) assays. This
study attempted to compare two different DNA extraction techniques namely salting
out and classic phenol-chloroform. MATERIALS AND METHODS: Qualification of two
different DNA extraction techniques for 634 clinical specimens highly suspected
of having mycobacterial infection was performed. Genomic DNA was extracted from
330 clinical samples using phenol-chloroform and 304 by non-toxic salting-out.
Qualification of obtained gDNA was done through amplification of internal
controls, beta-actin and beta-globin. RESULTS: beta-actin-positive was detected
in 279/330 (84%) and 272/304 (89%) samples by phenol-chloroform technique and
salting-out, respectively. PCR inhibitor was found for the gDNA of 13/304 (4%)
patient samples were negative by beta-actin and beta-globin tests via salting-out
technique in comparison with gDNAs from 27/330 (8.5%) samples extracted by phenol
chloroform procedure. No statistically significant difference was found between
phenol-chloroform technique and salting-out for 385 sputum, 29 bronchoalveolar
lavage (BAL), 105 gastric washing, and 38 body fluid (P=0.04) samples. This
illustrates that both techniques have the same quality for extracting gDNA.
CONCLUSION: This study discloses salting-out as a non-toxic DNA extraction
procedure with a superior time-efficiency and cost-effectiveness in comparison
with phenol-chloroform and it can be routinely used in resource-limited
laboratory settings.
PMID- 25852759
TI - Diagnostic Accuracy of Chest Ultrasonography versus Chest Radiography for
Identification of Pneumothorax: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Early detection of pneumothorax is critically important. Several
studies have shown that chest ultrasonography (CUS) is a highly sensitive and
specific tool. The present systematic review and meta-analysis was designed to
evaluate the diagnostic accuracy of CUS and chest radiography (CXR) for detection
of pneumothorax. MATERIALS AND METHODS: The literature search was conducted using
PubMed, EMBASE, Cochrane, CINAHL, SUMSearch, Trip databases, and review article
references. Eligible articles were defined as diagnostic studies on patients
suspected for pneumothorax who underwent chest computed tomography (CT) scan and
those assessing the screening role of CUS and CXR. RESULTS: The analysis showed
the pooled sensitivity and specificity of CUS were 0.87 (95% CI: 0.81-0.92; I2=
88.89, P<0.001) and 0.99 (95% CI: 0.98-0.99; I2= 86.46, P<0.001), respectively.
The pooled sensitivity and specificity of CXR were 0.46 (95% CI: 0.36-0.56; I2=
85.34, P<0.001) and 1.0 (95% CI: 0.99-1.0; I2= 79.67, P<0.001), respectively. The
Meta regression showed that the sensitivity (0.88; 95% CI: 0.82 - 0.94) and
specificity (0.99; 95% CI: 0.98 - 1.00) of ultrasound performed by the emergency
physician was higher than by non-emergency physician. Non-trauma setting was
associated with higher pooled sensitivity (0.90; 95% CI: 0.83 - 0.98) and lower
specificity (0.97; 95% CI: 0.95 - 0.99). CONCLUSION: The present meta-analysis
showed that the diagnostic accuracy of CUS was higher than supine CXR for
detection of pneumothorax. It seems that CUS is superior to CXR in detection of
pneumothorax, even after adjusting for possible sources of heterogeneity.
PMID- 25852761
TI - Evaluation of bronchoscopy complications in a tertiary health care center.
AB - BACKGROUND: Bronchoscopy is a technique of visualizing the inside of the airways
for diagnostic and therapeutic purposes. This study was performed to determine
the complications of bronchoscopy in a tertiary health-care center. MATERIALS AND
METHODS: This study had as descriptive cross sectional design. Four hundred adult
patients between 16 to 85 years, who underwent bronchoscopy with a same method
and same device and had no underlying disease, were consecutively enrolled.
RESULTS: Bronchoscopy complications were seen in 13 patients (3.25%) including
bleeding (four cases), pneumothorax (three cases), collapse (four cases), and
infection (two cases). There was no association between complications and age,
sex, bronchoscopy indications and findings (P > 0.05). CONCLUSION: According to
the obtained results, it may be concluded that bronchoscopy can be performed
safely whenever indicated. Complications occurred were minor and self limiting.
PMID- 25852762
TI - A piece of broken metal from intubation stylet retained in tracheobronchial tree:
a case report.
AB - Intubation stylets are still being used in many medical centers for difficult
intubations. Although very rare, it may break inside the trachea during
endotracheal intubation despite routine pre-assessments by anesthesiologists and
may surprisingly move deep into the tracheobronchial tree. In this case report,
we describe a rare complication after stylet or guide-wire intubation in a
patient in whom, a broken piece of metal guide remained in his tracheobronchial
tree for 3 days. A 62 year-old man was admitted to our hospital with the chief
complaint of functional class 3 dyspnea. The patient was a known case of chronic
obstructive pulmonary disease (COPD) from 3 years ago with a history of heavy
smoking (40 p/y) and oral opioid usage. We report a case with an unrecognized
broken piece of stylet in his trachea and left main bronchus, which was later
detected by CT scan and extracted before causing pressure rise symptoms in the
airway. Despite precise evaluation before use, signs of breakage in the stylet
may be missed and consequently, it may break inside the trachea and result in
serious complications. It is strongly recommended that the anesthesiologists pay
attention to the sounds and movements of the instruments. This article also
briefly reviews the most serious reported complications due to stylet breakage.
PMID- 25852763
TI - Huge hilar carcinoid tumor resected by transsternal pneumonectomy: a case
presentation.
AB - Carcinoid tumors comprise an uncommon group of pulmonary neoplasms with
neuroendocrine origin. In comparison with typical carcinoid tumors, atypical
tumors are less common and more aggressive. We present a 35-year old female with
atypical carcinoid tumor. The mass was located centrally and transsternal
pneumonectomy was performed to resect the tumor.
PMID- 25852764
TI - Unilateral pulmonary artery agenesis in an adult patient with cough and
hemoptysis: a case report.
AB - Unilateral pulmonary artery agenesis (UPAA) is an uncommon congenital anomaly and
most patients present in neonatal period with respiratory symptoms. Left-sided
pulmonary artery agenesis is less frequent than right-sided and is sometimes
associated with cardiac anomalies. We report a patient with a history of repaired
ventricular septal defect, who presented with cough and hemoptysis and the
diagnosis of UPAA was made.
PMID- 25852765
TI - Erratum to "Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by
Orally Administrated Cardiotoxin from Naja naja atra Venom".
AB - [This corrects the article DOI: 10.1155/2014/621756.].
PMID- 25852766
TI - Oldenlandia diffusa Promotes Antiproliferative and Apoptotic Effects in a Rat
Hepatocellular Carcinoma with Liver Cirrhosis.
AB - Oldenlandia diffusa (OD) is commonly used with various diseases such as cancer,
arthritis, and autoimmune disease. Liver cirrhosis is a predominant risk factor
for hepatocellular carcinoma (HCC). Here, we show that the therapeutic effect of
OD, which was investigated both in vitro and chemically, induced HCC model. OD
significantly enhanced apoptosis and antiproliferative activity and reduced
migration ability of HCC cells. In vivo, OD was treated twice a day for 28 days
after confirmed HCC model through 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG)
imaging. The survival in OD treated groups was shown to have a greater
therapeutic effect than the control group. 28 days after OD treatment, OD treated
groups resulted in a significant reduction in tumor number, size, (18)F-FDG
uptake, and serum levels such as alanine transaminase, aspartate transaminase,
and alkaline phosphate compared to the control group. Also, proliferated cells in
tumor sites by OD were reduced compared to the control group. Furthermore,
several rats in OD treated group survived over 60 days and liver morphology of
these rats showed the difference between tumor mass and normal tissue. These
results suggest that OD may have antiproliferative activity, inhibition of
metastasis, and apoptotic effects in chemically induced HCC model and can have
the potential use for clinical application as anticancer drug of the herbal
extract.
PMID- 25852767
TI - Vitis vinifera (Muscat Variety) Seed Ethanolic Extract Preserves Activity Levels
of Enzymes and Histology of the Liver in Adult Male Rats with Diabetes.
AB - The effect of V. vinifera seeds on carbohydrate metabolizing enzymes and other
enzymes of the liver in diabetes is currently unknown. We therefore investigated
changes in the activity levels of these enzymes following V. vinifera seed
extract administration to diabetic rats. Methods. V. vinifera seed ethanolic
extract (250 and 500 mg/kg/day) or glibenclamide (600 MUg/kg/day) was
administered to streptozotocin-induced male diabetic rats for 28 consecutive
days. At the end of treatment, liver was harvested and activity levels of various
liver enzymes were determined. Levels of thiobarbituric acid reactive substances
(TBARS) were measured in liver homogenates and liver histopathological changes
were observed. Results. V. vinifera seed ethanolic extract was able to prevent
the decrease in ICDH, SDH, MDH, and G-6-PDH and the increase in LDH activity
levels in liver homogenates. The seed extract also caused serum levels of ALT,
AST, ALP, ACP, GGT, and total bilirubin to decrease while causing total proteins
to increase. Additionally, the levels of ALT, AST, and TBARS in liver homogenates
were decreased. Histopathological changes in the liver were reduced. Conclusion.
Near normal activity levels of various enzymes and histology of the liver
following V. vinifera seed ethanolic extract administration may be due to
decrease in liver oxidative stress in diabetes.
PMID- 25852768
TI - Multidetector CT with 3-dimensional volume rendering in the evaluation of the
spine in patients with Neurofibromatosis type 1: a retrospective review in 73
patients.
AB - INTRODUCTION: Neurofibromatosis type 1 (NF-1) may involve the spine as various
abnormalities including bony dysplasia, scoliosis, and nerve sheath tumors.
Surgery may be performed for stabilization of the spine. We have seen an increase
in requests for multidetector CT (MDCT) imaging with the (three-dimensional) 3D
volume rendered (VR) images in patients evaluated at our institution. We,
therefore, investigated how MDCT could be best utilized in this patient
population. METHODS: Seventy-three patients with NF-1 were identified in whom
MDCT imaging was performed for diagnostic, pre-operative, or post-operative
evaluation of spinal abnormalities. True axial source images and two dimensional
(2D) orthogonal reconstructed MDCT images, as well as the VR images, were
compared with plain radiographs and MRI. In addition, the MDCT study was compared
to the VR images. These studies were reviewed to compare assessment of A) bony
abnormalities such as remodeling from dural ectasia, dysplasia, and fusion, B)
abnormal spinal curvature, C) nerve sheath tumors, and D) surgical
instrumentation. RESULTS: When compared to plain radiographs, the MDCT and VR
images were rated as helpful for evaluating the abnormalities of the spine in 19
of 24 patients for a total of 30 findings. This included the following categories
A) (n = 6), B) (n = 5), C) (n = 7), and D) (n = 12). Compared to MR, the MDCT and
VR study was helpful in evaluating the findings of NF-1 in 24 of 36 patients for
a total of 40 findings. This included the following categories A) (n = 12), B) (n
= 10), C) (n = 3), and D) (n = 15). When the VR images were compared to the
orthogonal MDCT, the VR images was rated as helpful in 41 of 73 patients for a
total of 60 findings, including the following categories: A) (n = 11), B) (n =
24), C) (n = 0), and D) (n = 25). CONCLUSION: MDCT has distinct advantages over
plain radiographs and MR imaging, and the VR images over MDCT in the evaluation
of the spine in patients with NF-1, especially for the assessment of bony
abnormalities, abnormal spinal curvature, and spinal instrumentation.
PMID- 25852769
TI - Nutritional, chemical and microbiological changes during fermentation of tarhana
formulated with different flours.
AB - BACKGROUND: Tarhana is a fermented cereal product that is used for the
preparation of one of the favourite soups in Turkish cuisine. Tarhana is a
mixture of wheat flour, yoghurt, baker's yeast, salt, and various vegetables,
spices and seasonings. It is obtained by mixing all ingredients in the recipe and
afterwards the mixture is let to ferment at room temperature. Following
fermentation tarhana is dried or frozen for long term storage. In this study, to
improve the nutritional benefits of tarhana, whole wheat and chickpea flours were
used as the sole source of flour. The changes in the phytic acid content,
proteins and fermentation products were investigated in addition to some
microbiological and chemical characteristics. RESULTS: The effect of flour type
on the phytic acid content was significant. No differences were observed in the
glutenin band patterns of the wheat and whole wheat flours and their tarhana
samples. Conversely, for the gliadin fractions, the bands of the wheat and whole
wheat flours were more intense than their tarhana samples. The changes in the
glutelin and prolamin fractions of the chickpea flour and the resultant tarhana
dough were similar to the glutenin and gliadin fractions of wheat and whole wheat
flours and their tarhana samples. In all samples, the yeasts displayed an
undulant growth pattern and the effect of flour type and fermentation time on
yeast growth was significant (P < 0.01). The effect of flour type (P < 0.01) and
fermentation time (P < 0.05) on mesophilic LAB was significant. Similar
behaviours were observed with the mesophilic LAB in all samples and their numbers
remained closed to their initial numbers. The growth of thermophilic LAB was not
influenced by the flour type, but the effect of fermentation time was significant
(P < 0.01). CONCLUSIONS: The whole wheat and chickpea tarhana are found to be
good alternatives to classical tarhana with their higher nutritional benefits but
further investigations are needed for the assessment of their sensory properties.
PMID- 25852770
TI - The neurotoxic effects of ampicillin-associated gut bacterial imbalances compared
to those of orally administered propionic acid in the etiology of persistent
autistic features in rat pups: effects of various dietary regimens.
AB - HYPOTHESIS: A healthy gut with normal intestinal microflora is completely
disrupted by oral antibiotics. The byproducts of harmful gut bacteria can
interfere with brain development and may contribute to autism. Strategies to
improve the gut microflora profile through dietary modification may help to
alleviate gut disorders in autistic patients. METHOD: Sixty young male western
albino rats were divided into six equal groups. The first group served as the
control; the second group was given an oral neurotoxic dose of propionic (PPA)
(250 mg/kg body weight/day) for three days. The third group received an
orogastric dose of ampicillin (50 mg/kg for three weeks) with a standard diet.
Groups 4, 5 and 6 were given an orogastric dose of ampicillin and fed high
carbohydrate, high-protein and high-lipid diets, respectively, for 10 weeks.
Biochemical parameters related to oxidative stress were investigated in brain
homogenates from each group. RESULT: The microbiology results revealed
descriptive changes in the fecal microbiota of rats treated with ampicillin
either alone or with the three dietary regimens. The results of PPA acid and
ampicillin treatment showed significant increases in lipid peroxidation and
catalase with decreases in glutathione and potassium compared with levels in the
control group. A protein-rich diet was effective at restoring the glutathione
level, while the carbohydrate-rich diet recovered lipid peroxidation and catalase
activity. In addition, the three dietary regimens significantly increase the
potassium level in the brain tissue of the test animals. Lactate dehydrogenase
was remarkably elevated in all groups relative to the control. No outstanding
effects were observed in glutathione S-transferase and creatine kinase.
CONCLUSION: The changes observed in the measured parameters reflect the
neurotoxic effects of PPA and ampicillin. Lipid peroxide and catalase activity
and the levels of glutathione and potassium are satisfactory biomarkers of PPA
and ampicillin neurotoxicity. Based on the effects of the three dietary regimens,
a balanced diet can protect against PPA or ampicillin-induced neurotoxicity that
might induce autistic traits. These outcomes will help efforts directed at
controlling the prevalence of autism, a disorder that has recently been
associated with PPA neurotoxicity.
PMID- 25852771
TI - Establishing research priorities for patient safety in emergency medicine: a
multidisciplinary consensus panel.
AB - BACKGROUND: Patient safety in the context of emergency medicine is a relatively
new field of study. To date, no broad research agenda for patient safety in
emergency medicine has been established. The objective of this study was to
establish patient safety-related research priorities for emergency medicine.
These priorities would provide a foundation for high-quality research, important
direction to both researchers and health-care funders, and an essential step in
improving health-care safety and patient outcomes in the high-risk emergency
department (ED) setting. METHODS: A four-phase consensus procedure with a
multidisciplinary expert panel was organized to identify, assess, and agree on
research priorities for patient safety in emergency medicine. The 19-member panel
consisted of clinicians, administrators, and researchers from adult and pediatric
emergency medicine, patient safety, pharmacy, and mental health; as well as
representatives from patient safety organizations. In phase 1, we developed an
initial list of potential research priorities by electronically surveying a
purposeful and convenience sample of patient safety experts, ED clinicians,
administrators, and researchers from across North America using contact lists
from multiple organizations. We used simple content analysis to remove
duplication and categorize the research priorities identified by survey
respondents. Our expert panel reached consensus on a final list of research
priorities through an in-person meeting (phase 3) and two rounds of a modified
Delphi process (phases 2 and 4). RESULTS: After phases 1 and 2, 66 unique
research priorities were identified for expert panel review. At the end of phase
4, consensus was reached for 15 research priorities. These priorities represent
four themes: (1) methods to identify patient safety issues (five priorities), (2)
understanding human and environmental factors related to patient safety (four
priorities), (3) the patient perspective (one priority), and (4) interventions
for improving patient safety (five priorities). CONCLUSION: This study
established expert, consensus-based research priorities for patient safety in
emergency medicine. This framework could be used by researchers and health-care
funders and represents an essential guiding step towards enhancing quality of
care and patient safety in the ED.
PMID- 25852772
TI - A pilot study to identify clinical predictors for wrist fractures in adult
patients with acute wrist injury.
AB - BACKGROUND: To date, no clinical decision rules for acute wrist injuries are
available. In the past, clinical decision rules for the knee, ankle and spine
injuries have been developed and validated. Implementation of these rules
resulted in standardised clinical assessment at the emergency department and a
substantial reduction of radiographic diagnostics. The objective of the study was
to identify predictors for wrist fractures in patients with acute wrist injury
which might potentiate a clinical decision rule in the future. This is a
prospective pilot study in adult patients presenting with acute wrist injury at
the emergency department of the Canisius-Wilhelmina Hospital in the Netherlands.
METHODS: Clinical variables were collected in a case report file by emergency
physicians. Radiography was ordered according to common practice to confirm or
rule out the presence of fractures. Independent associations between the presence
of clinical variables and wrist fractures were calculated. Multivariable analysis
was performed in order to quantify sensitivity and specificity for fracture
prediction. RESULTS: A total of 63 wrist fractures were detected in the study
population of 95. Age over 55 years, inability to carry weight directly after
trauma, support of injured wrist by the contralateral hand for pain relief,
presence of swelling and/or hematoma, visible wrist deformity and reduced range
of motion were associated with the presence of a wrist fracture. CONCLUSIONS: Our
study identified clinical predictors for wrist fractures in patients with acute
wrist injury. Future studies are needed for justification of evidence-based wrist
assessment and identification of a 100% sensitive decision rule for wrist
fractures.
PMID- 25852773
TI - Radiologic diagnostic procedures in severely injured patients - is only whole
body multislice computed tomography the answer?
AB - BACKGROUND: Whole-body multislice computed tomography (WB-MSCT) has become an
important diagnostic tool in the early treatment phase of severely injured
patients. The optimal moment of WB-MSCT's use during this treatment phase remains
unclear. Many trauma centers use WB-MSCT in addition to conventional radiographs,
while some trauma centers use WB-MSCT as the only radiological tool. The aim of
this study was to determine the differences between these two protocols and to
answer the question of whether conventional radiographs can still be used in the
safe treatment of polytrauma patients. METHODS: Patients from the TraumaRegister
DGU(r) with an injury severity score (ISS) of >=16 were included. Group I
received conventional radiographs and focused assessment with sonography in
trauma (FAST) prior to a WB-MSCT, and group II received an initial WB-MSCT and
FAST. Both groups were compared concerning treatment time and outcome. RESULTS: A
total of 3,995 patients in group I were compared to 4,025 patients in group II.
There were no differences in ISS (29.97 vs. 29.94), gender (male: 73.5% vs.
72.8%), age (45.47 vs. 45.12 years), or calculated mortality (21.41% vs. 21.44%).
Time needed in the resuscitation room was slightly longer in group I (72 vs. 64
min); the durations until admittance to the ICU and arrival to the OR were not
significantly different between the groups. There was no difference in mortality
(18.2% vs. 18.4%) or the standardized mortality ratio (SMR) (0.85 vs. 0.86).
CONCLUSIONS: WB-MSCT plays an inherent role in the treatment of multiple-injured
patients. However, the use of WB-MSCT as the only diagnostic method in the
resuscitation room is not needed. Conventional radiographs and FAST followed by
WB-MSCT can be performed in the early resuscitation phase without impairing
patient outcomes. This approach enables the emergency room team to perform life
saving procedures - chest-tube insertion, laparotomy, cardiopulmonary
resuscitation -immediately and simultaneous. Nevertheless, randomized multi
center trials are needed to determine the comparability and effectiveness of
these algorithms.
PMID- 25852774
TI - A retrospective observational study of medical incident command and decision
making in the 2011 Oslo bombing.
AB - BACKGROUND: A core task for commanders in charge of an emergency response
operation is to make decisions. The purposes of the study were to describe what
critical decisions the ambulance commander and the medical commander make in a
mass casualty incident response and to explore what the underlying conditions
affecting decision-making are. The study was conducted in the context of the 2011
government district terrorist bombing in Norway. METHODS: The study was a
retrospective, descriptive observational study collecting data through
participating observation, semi-structured interviews, and recordings of
emergency medical services' radio communications. Analysis was conducted using
systematic text condensation. The ambulance commander was interviewed using the
critical decision method. RESULTS: The medical emergency response lasted 6.5 h,
with little clinical activity after 2 h. Most critical decisions were made within
the first 30 min, with the ambulance commander making the bulk of decisions.
Situation assessment and underlying uncertainties strongly affected decision
making, but there was a mutual interaction between these three factors that
developed throughout the different stages of the operation. Knowledge and
experience were major determinants of how easily commanders picked up sensory
cues and translated them into situation assessments. The number and magnitude of
uncertainties were largest in the development stage, after most of the critical
decisions had been made. CONCLUSIONS: In the studied mass casualty incident, the
commanders made most critical decisions in the early stages of the emergency
response when resources did not meet demand. Decisions were made under
significant uncertainty and time pressure. Ambulance and medical commanders
should be prepared to make situation assessments and decisions early and be ready
to adjust as uncertainties are reduced.
PMID- 25852775
TI - 'Need-to-Know' emergency medicine articles of 2014.
AB - Every year, thousands of articles are published in numerous medical journals that
relate to the clinical practice of medicine. However, it is impossible for a
single clinician to stay abreast of the literature, let alone to determine which
articles should change daily practice. Physicians in our department have searched
the emergency medicine and the specialty literature of 2014 to determine which
articles are most relevant to the clinical practice of emergency medicine,
summarized them, and listed key take-home points from these 'need-to-know'
articles.
PMID- 25852776
TI - Multi-organ dysfunction secondary to severe wasp envenomation.
AB - Wasp sting is not an uncommon incident. Around 56% to 94% of the population is
stung at least once in their lifetime by a member of the order Hymenoptera which
includes wasps, bees, and ants. The response to a wasp sting may vary from mild
local reaction to severe systemic and anaphylactic reactions. The clinical
picture and mortality rate tend to be more severe in adults compared to children.
We present a 32-year-old agricultural worker who was bitten by multiple wasps
while on a coconut tree. In spite of the heavy load of venom due to the multiple
bites, the patient did not develop anaphylaxis. However, a delayed reaction did
occur within 48 h in the form of severe multi-organ dysfunction. There was
significant improvement by around 2 weeks; but it took another 6 months for the
serum creatinine to normalize. This case highlights the occupational risk of
Hymenoptera envenomation, the life-threatening complications that may follow and
which may even be delayed as was the case with this patient, and the value of
emergency care and intensive management which can result in a favorable clinical
outcome.
PMID- 25852777
TI - Erratum: Emerging topics in FXTAS.
AB - [This corrects the article DOI: 10.1186/1866-1955-6-31.].
PMID- 25852778
TI - Improving N1 classification by grouping EEG trials with phases of pre-stimulus
EEG oscillations.
AB - A reactive brain-computer interface using electroencephalography (EEG) relies on
the classification of evoked ERP responses. As the trial-to-trial variation is
evitable in EEG signals, it is a challenge to capture the consistent
classification features distribution. Clustering EEG trials with similar features
and utilizing a specific classifier adjusted to each cluster can improve EEG
classification. In this paper, instead of measuring the similarity of ERP
features, the brain states during image stimuli presentation that evoked N1
responses were used to group EEG trials. The correlation between momentary phases
of pre-stimulus EEG oscillations and N1 amplitudes was analyzed. The results
demonstrated that the phases of time-frequency points about 5.3 Hz and 0.3 s
before the stimulus onset have significant effect on the ERP classification
accuracy. Our findings revealed that N1 components in ERP fluctuated with
momentary phases of EEG. We also further studied the influence of pre-stimulus
momentary phases on classification of N1 features. Results showed that linear
classifiers demonstrated outstanding classification performance when training and
testing trials have close momentary phases. Therefore, this gave us a new
direction to improve EEG classification by grouping EEG trials with similar pre
stimulus phases and using each to train unit classifiers respectively.
PMID- 25852779
TI - Psychomotor functions at various weeks of chronic renal failure in rats.
AB - In chronic renal failure there is a gradual retention of substances in the
tissues and body fluids, called as uremic retention toxins, which can bring about
a number of biochemical activities in the body. Chronic renal insufficiency also
leads to progressive behavioural conflict. Uremic toxins can affect both the
central and the peripheral nervous system. Uremic encephalopathy is also
associated with problems in cognition and memory. To study the psychomotor
functional disorders in rats with progressive chronic renal failure surgical
nephrectomy was done by resection method. The animals were grouped into two
control groups, Sham control (SC) and normal control (NC) and two uremic groups,
moderate uremia (GM) and severe uremia (GS). Psychomotor analysis was done by
passive avoidance and open field in these animals at 4, 8, 12, and 16 weeks.
After the incubation period, the nephrectomised groups (GM and GS) showed
significant changes in exploratory, locomotor and emotional behaviour when
compared to the controls (NC and SC). Psychomotor changes involve poor cognition,
reduced memory, reduced locomotor activity and decreased exploratory drive and
emotional disturbance like increased fear during the initial stages. During the
later stages a restless behaviour was noticed, associated with diminished fear.
PMID- 25852780
TI - Bifurcation dynamics and determination of alternate cell fates in bipotent
progenitor cells.
AB - The gene regulatory networks in which two lineage-affiliated transcription
factors, such as GATA1 and PU.1, inhibit each other but activate themselves so as
to regulate the choice between alternative cell fates have been extensively
studied. These simple networks can generate bistability and explain the
transitions between the alternative cell fates. The commitment of a progenitor
cell to a new fate corresponds to the occurrence of different types of
bifurcations, depending on if a system is symmetrical and how perturbations
affect the system. Here we take a general modeling and analyzing approach and
show that the lateral inhibition with symmetry and asymmetry can lead to
different bifurcation dynamics. Especially, if cell fate decision-making is
initiated with asymmetry or symmetry-breaking perturbations, a progenitor cell
pre-patterns itself into a polarized cell, depending on the asymmetry or symmetry
breaking perturbations. This study may help us understand the fundamental
features of binary cell fate decisions more clearly and further apply to a wider
range of decision-making processes.
PMID- 25852781
TI - EEG-based investigation of brain connectivity changes in psychotic patients
undergoing the primitive expression form of dance therapy: a methodological pilot
study.
AB - Primitive expression (PE) is a form of dance therapy (DT) that involves an
interaction of ethologically and socially based forms which are supplied for re
enactment. There exist very few studies of DT applications including in their
protocol the measurement of neurophysiological parameters. The present pilot
study investigates the use of the correlation coefficient (rho) and mutual
information (MI), and of novel measures extracted from rho and MI, on
electroencephalographic (EEG) data recorded in patients with schizophrenia while
they undergo PE DT, in order to expand the set of neurophysiology-based
approaches for quantifying possible DT effects, using parameters that might
provide insights about any potential brain connectivity changes in these patients
during the PE DT process. Indication is provided for an acute potentiation
effect, apparent at late-stage PE DT, on the inter-hemispheric connectivity in
frontal areas, as well as for attenuation of the inter-hemispheric connectivity
of left frontal and right central areas and for potentiation of the intra
hemispheric connectivity of frontal and central areas, bilaterally, in the
transition from early to late-stage PE DT. This pilot study indicates that by
using EEG connectivity measures based on rho and MI, the set of useful
neurophysiology-based approaches for quantifying possible DT effects is expanded.
In the framework of the present study, the causes of the observed connectivity
changes cannot be attributed with certainty to PE DT, but indications are
provided that these measures may contribute to a detailed assessment of
neurophysiological mechanisms possibly being affected by this therapeutic
process.
PMID- 25852782
TI - An improved localization algorithm based on genetic algorithm in wireless sensor
networks.
AB - Wireless sensor network (WSN) are widely used in many applications. A WSN is a
wireless decentralized structure network comprised of nodes, which autonomously
set up a network. The node localization that is to be aware of position of the
node in the network is an essential part of many sensor network operations and
applications. The existing localization algorithms can be classified into two
categories: range-based and range-free. The range-based localization algorithm
has requirements on hardware, thus is expensive to be implemented in practice.
The range-free localization algorithm reduces the hardware cost. Because of the
hardware limitations of WSN devices, solutions in range-free localization are
being pursued as a cost-effective alternative to more expensive range-based
approaches. However, these techniques usually have higher localization error
compared to the range-based algorithms. DV-Hop is a typical range-free
localization algorithm utilizing hop-distance estimation. In this paper, we
propose an improved DV-Hop algorithm based on genetic algorithm. Simulation
results show that our proposed algorithm improves the localization accuracy
compared with previous algorithms.
PMID- 25852783
TI - 3D DWT-DCT and Logistic MAP Based Robust Watermarking for Medical Volume Data.
AB - Applying digital watermarking technique for the security protection of medical
information systems is a hotspot of research in recent years. In this paper, we
present a robust watermarking algorithm for medical volume data using 3D DWT-DCT
and Logistic Map. After applying Logistic Map to enhance the security of
watermarking, the visual feature vector of medical volume data is obtained using
3D DWT-DCT. Combining the feature vector, the third party concept and Hash
function, a zero-watermarking scheme can be achieved. The proposed algorithm can
mitigate the illogicality between robustness and invisibility. The experiment
results show that the proposed algorithm is robust to common and geometrical
attacks.
PMID- 25852784
TI - Study on bayes discriminant analysis of EEG data.
AB - OBJECTIVE: In this paper, we have done Bayes Discriminant analysis to EEG data of
experiment objects which are recorded impersonally come up with a relatively
accurate method used in feature extraction and classification decisions. METHODS:
In accordance with the strength of alpha wave, the head electrodes are divided
into four species. In use of part of 21 electrodes EEG data of 63 people, we have
done Bayes Discriminant analysis to EEG data of six objects. Results In use of
part of EEG data of 63 people, we have done Bayes Discriminant analysis, the
electrode classification accuracy rates is 64.4%. CONCLUSIONS: Bayes Discriminant
has higher prediction accuracy, EEG features (mainly alphawave) extract more
accurate. Bayes Discriminant would be better applied to the feature extraction
and classification decisions of EEG data.
PMID- 25852785
TI - Ontological Security in Nursing Homes for Older Persons - Person-Centred Care is
the Power of Balance.
AB - INTRODUCTION: The Swedish national guidelines for elderly care describe how older
persons should be able to trust that their care is permeated with security.
Different theoretical perspectives can be found that describe what creates
security. Many studies have been done about security. However, few studies have
explicitly asked older persons what security in nursing homes means to them. AIM:
The aim of the study was to describe how older persons in nursing homes talked
and reflected about security in their daily lives. METHOD: Nine older persons
were interviewed in, in-depth interviews one to three times and the resulting
data was analysed using content analysis. RESULTS: The older persons adapted to
having their own needs and those of the other older persons met and to the staff
routines which created a sense of security. At the same time, they longed for
security in which they could trust themselves and create their own daily life.
Further to have a sense of belonging and of being liked for created an internal,
interpersonal and external security. This can be linked to an ontological
security which means having a sense of confidence in the continuity of self
identity and order in events, a being in the world. CONCLUSION: Person-centred
instead of institution- centred care can provide the balance of power that allows
the older person to obtain ontological security in which the staff's ability to
create a relationship with the older persons becomes crucial.
PMID- 25852786
TI - Prevalence of latent tuberculosis infection and associated risk factors among
1557 nursing students in a context of low endemicity.
AB - INTRODUCTION: The risk of tuberculosis (TBC) in nurses is related to its
incidence in the general population. Nursing students involved in clinical
training could be exposed to occupational risks similar to those of healthcare
workers (HCWs). To better understand the epidemiology of nosocomial TBC among
nurses in a context of low endemicity, we recruited a cohort of young nursing
trainees at the Second University of Naples. METHODS: A screening programme for
LTBI in nursing students was conducted between January 2012 and December 2013, at
the Second University of Naples, with clinical evaluations, tuberculin skin test
(TST) and, in positive TST student, the interferon-g release assays (IGRA).
Putative risk factors for LTBI were assessed by a standardized questionnaire.
RESULTS: 1577 nursing students attending the Second University of Naples have
been submitted to screening programme for TBC. 1575 have performed TST as first
level test and 2 Quantiferon test (QFT). 19 students were TST positive and
continued the diagnostic workup practicing QFT, that was positive in 1 student.
Of the 2 subjects that have practiced QFT as first level test only 1 was
positive. In 2 students positive to QFT test we formulated the diagnosis of LTBI
by clinical and radiographic results. CONCLUSION: The prevalence of LTBI among
nursing students in our study resulted very low. In countries with a low
incidence of TBC, the screening programs of healthcare students can be useful for
the early identification and treatment of the sporadic cases of LTBI.
PMID- 25852787
TI - Omental pregnancy: case report and review of literature.
AB - Pregnancy, the implantation of a fertilized ovum outside the endometrial cavity,
occurs in 1.5%-2% of pregnancies. It is one of the major causes (about 6%) of
maternal death during the first trimester of pregnancy. The remaining 5% implant
in the ovary, peritoneal cavity, within the cervix, and the omental pregnancy is
the least common form of abdominal pregnancies. A review of the literature on
Medline for the period 1958-2012 reported only 16 cases of omental pregnancy.
Here we report a case of primary omental pregnancy in a nulliparous woman. A 24
year-old woman gravid 1, para 0, with lower abdominal pain. Her last menstrual
period occurred 8 weeks before the visit. The physical examination revealed
abdominal tenderness in the lower quadrants, she was not bleeding. Transvaginal
ultrasound showed: a free anechoic/hypoechoic area of 30 x 57 mm in the pouch of
Douglas and the endometrium was homogeneus with a thickness of 12 mm and no
evidence of gestational sac in the uterine cavity. Laboratory data revealed a
normal cell blood count and beta hcg levels of 8047 IU / L. Because of continuing
abdominal pain and a diagnosis of ectopic pregnancy a diagnostic laparoscopy was
performed, which showed hemoperitoneum. Further inspection of abdominal cavity
revealed a bloody lesion that was tenaciously adherent to the omentum, using non
traumatic laparoscopic forceps and bipolar scissors we carefully removed a
friable mass of about 30 mm from the omental attachments. Histological
examination showed the presence of blood clot material mixed with trophoblastic
tissue. Ultrasound evaluation and and hCG assessment are important to determine
the extrauterine location of the ectopic pregnancy but the early diagnosis of
abdominal pregnancy requires also a laparoscopic evaluation and, as our case has
highlighted, thorough abdominal exploration especially in the absence of adnexal
findings when ectopic pregnancy is highly suspected. Early diagnosis of omental
pregnancy is difficult but essential to reduce the high mortality risk for the
mother.
PMID- 25852788
TI - [Management of cervical cancer during pregnancy: report of 05 cases].
PMID- 25852789
TI - Management of a rare case of arrhythmogenic right ventricular dysplasia in
pregnancy: a case report.
AB - Arrhythmogenic right ventricular dysplasia is a rare but not exceptional
inherited cardiomyopathy characterized by fibrofatty replacement of the
myocardium of the right ventricular which could lead to serious arrhythmia and
sudden death. Only a few cases of pregnancies with ARVD have been reported. The
aim of this case presentation is to describe the clinical characteristics and
anesthetics specificities in management of this disease in pregnancy and in
delivery. We report the case of a young woman aged 28 years old with a past
history of ARVD treated by medical treatment with radiofrequency ablation. This
patient was pregnant and it was scheduled for cesarean section delivery.
Preoperative evaluation showed a well tolerated pregnancy inspite of the severity
of the ARVD. It was a severe form of ARVD because of RV dilation, the spread of
the disease to LV and the history of ventricular tachycardia during an attempted
of ablation by radio frequency. The treatment received by the patient was kept
until the day of surgery. The act took place under general anesthesia. The
postoperative period was uneventful and morphine titration was used for pain
relief. The patient exits the hospital 3 days after delivery and breastfeeding
was forbidden. We should pay attention on this disease witch is not yet well
known and witch is highly risky in the peri-partum period. Even if pregnancy may
be tolerated in moderate forms of ARVD, conception and delivery sould be
discouraged especially in severe forms.
PMID- 25852790
TI - [A neuroleptic malignant syndrome complicated by subarachnoid hemorrhage and
revealing cerebral vasculitis].
PMID- 25852791
TI - [Sero-epidemiological study of canine leishmaniasis in central Morocco].
PMID- 25852792
TI - [Pure tibiotalar dislocation: about a case with review of the literature].
PMID- 25852793
TI - [General medicine perceived by the students of the Faculty of Medicine of Sousse
(Tunisia)].
PMID- 25852794
TI - An unusual manifestation of hyperkalemia.
PMID- 25852795
TI - [A saccular aneurysm of the abdominal aorta revealing Behcet disease: when to
operate?].
PMID- 25852796
TI - Menstrual hygiene management amongst schoolgirls in the Rukungiri district of
Uganda and the impact on their education: a cross-sectional study.
AB - INTRODUCTION: An increasing number of studies have found that girls in low-income
settings miss or struggle at school during menstruation if they are unable to
manage their menstrual hygiene effectively. This study explores the menstrual
hygiene practices and knowledge of girls at rural government primary schools in
the Rukungiri district in Uganda and assesses the extent to which poor menstrual
hygiene management (MHM) affects their education. METHODS: A self-administered
questionnaire was completed by schoolgirls in six government-run primary schools
in the Rukungiri district. Focus groups were held with girls from each school and
semi-structured interviews were conducted with headteachers and female teachers
from the participating schools. A toilet assessment was also conducted in each
school. RESULTS: One hundred and forty schoolgirls completed the questionnaire.
The girls reported a lack of access to adequate resources, facilities and
accurate information to manage their menstrual hygiene effectively at school.
They reported that, as a result, during menstruation they often struggle at
school or miss school. Eighty-six girls (61.7%) reported missing school each
month for menstrual-related reasons (mean 1.64, range 0-10, SD. 1.84).
CONCLUSION: It is common for girls who attend government-run primary schools in
the Rukungiri district to miss school or struggle in lessons during menstruation
because they do not have access to the resources, facilities, or information they
need to manage for effective MHM. This is likely to have detrimental effects on
their education and future prospects. A large-scale study is needed to explore
the extent of this issue.
PMID- 25852797
TI - Severe Klippel-Feil syndrome with Mondini malformation of inner ear.
AB - Klippel-Feil syndrome is defined as the fusion of cervical vertebra with
associated congenital anomalies but was rarely reported to be associated with
Mondini Malformation. We report a newborn girl with severe neck extension,
computed tomography (CT) of the neck after birth showed fusion of the fifth,
sixth, and seventh cervical vertebrae, compatible with Klippel-Feil Syndrome and
CT temporal bone showed choclear dysplasia with incomplete number of turns that
is compatible with Mondini Malformation.
PMID- 25852798
TI - Knowledge and practices towards rabies and determinants of dog rabies vaccination
in households: a cross sectional study in an area with high dog bite incidents in
Kakamega County, Kenya, 2013.
AB - INTRODUCTION: An estimated 55,000 people die from rabies annually. Factors
promoting dog vaccination, estimates of vaccination coverage and knowledge on
rabies are important for effective rabies control. We sought to establish these
estimates at household (HH) level and whether rabies knowledge is associated with
proper control practices. METHODS: Cross-sectional cluster survey with two-stage
sampling was employed in Kakamega County to enroll HH members above 18 years. A
set of questions related to rabies knowledge and practice were used to score
participant response. Score above the sample mean was equated to adequate
knowledge and proper practices respectively. Independent t-test was used to
evaluate the differences of sample mean scores based on dog vaccination status.
Bivariate analysis was used to associate knowledge to practices. RESULTS: Three
hundred and ninety HHs enrolled and had a population of 754 dogs with 35% (n =
119) HH having vaccinated dogs within past 12 months. Overall mean score for
knowledge was 7.0 (+/-2.8) with range (0-11) and 6.3 (+/-1.2) for practice with
range (0-8). There was a statistically significant difference in mean knowledge
(DF = 288, p < 0.01) and practice (DF = 283, p = 0.001) of HH with vaccinated
dogs compared to ones with unvaccinated dogs. Participants with adequate rabies
knowledge were more likely to have proper health seeking practices 139 (80%) (OR
= 3.0, 95% CI = 1.4-6.8) and proper handling practices of suspected rabid dog 327
(88%) (OR = 5.4, 95% CI = 2.7-10.6). CONCLUSION: Rabies vaccination below the 80%
recommended for herd immunity. Mass vaccination campaign needed. More innovative
ways of translating knowledge into proper rabies control practice are warranted.
PMID- 25852799
TI - Collateral benefits arising from mass administration of azithromycin in the
control of active trachoma in resource limited settings.
AB - INTRODUCTION: The benefits of the use of antibiotics in the mass treatment for
active trachoma and other diseases have been documented, but the secondary
effects arising from such a programme have not been fully elucidated. The purpose
of this study was to investigate the potential secondary benefits arising from
the use of azithromycin in mass treatment of active trachoma in an economically
challenged Kenyan nomadic community. METHODS: Health information reports for
January 2005 to December 2010 were reviewed to determine the annual trends of
infectious diseases in the two districts, Narok and Transmara. The year 2007 was
considered as the baseline for mass drug administration (MDA). Odds ratios (OR)
were used to describe the association. RESULTS: The mass distribution coverage in
Narok was 83% in 2008, 74% in 2009 and 63% in 2010. The odds for malaria (OR =
1.13; 95% CI 1.12-1.14), diarrhoeal diseases (OR = 1.04; 95% CI 1.01-1.06),
urinary tract infections (UTIs) (OR = 1.21; 95% CI 1.17-1.26), intestinal worms
(OR, 4.98; 95% CI 4.68-5.3), and respiratory diseases other than pneumonia (OR,
1.15; 95% CI 1.13-1.16) were higher after three rounds of mass treatment,
indicating a better outcome. Before the intervention, there was a reducing trend
in the odds for respiratory diseases. In Transmara (control), there was an
increase in odds for malaria, respiratory infections, UTIs and intestinal worms.
The odds for diarrhoeal diseases, skin diseases and pneumonia decreased
throughout the study period. CONCLUSION: Mass distribution of azithromycin may
have contributed to the decrease in the prevalence of the respiratory infections
in Narok District.
PMID- 25852800
TI - Comparative functional exercise capacity of patients with type 2-diabetes and
healthy controls: a case control study.
AB - INTRODUCTION: Functional Exercise Capacity (FEC) is a valid measure of physical
fitness in health and disease. However, there is paucity of studies on FEC in
African patients with Type-2 Diabetes (T2D). This study compared FEC between
patients with T2D and healthy controls. METHODS: Thirty five patients with T2D
(18 men, 17 women) and 35 (16 men, 19 women) age-sex matched healthy controls
participated in this case-control study. Anthropometric and demographic
characteristics and cardiovascular parameters were measured following standard
procedures. A glucometer was used to determine the Fasting Blood Glucose (FBG)
level following at least 8 hours of overnight fasting. FEC was assessed using the
Six-Minute Walk Test (6MWT) while Hand Grip Strength (HGS) test was measured with
an electronic dynamometer. Data were analyzed using descriptive and inferential
statistics. Alpha level was set at p< 0.05. RESULTS: Patients with T2D and
controls were similar in age (p > 0.05). There were significant differences in
the distance covered during 6MWT between patients and controls (t= 0.329; p
=0.03), exercise capacity (t = 0.329; p = 0.03), FBG (t = 7.403; p = 0.001),
systolic and diastolic blood pressure (t = 12.56; p = 0.001 and t = 27.23; p =
0.001) respectively. There were significant inverse relationships between 6MWD
and Body mass index (r = -0.39; p = 0.02) and FBS(r = -0.51; p = 0.02) in
patients with type-2 respectively. No significant association was found between
exercise capacity and HGS (p > 0.05). CONCLUSION: Patients with type-2 diabetes
demonstrated lower functional exercise capacity than healthy controls. High body
mass index and fasting blood glucose were significantly associated with lower
functional exercise capacity.
PMID- 25852801
TI - [Hoffa ligament ossification: final evolution of the Hoffa disease (about a case
with review of the literature)].
PMID- 25852802
TI - Awareness, treatment, control of hypertension and utilization of health care
services following screening in the North-central region of Burkina Faso.
AB - INTRODUCTION: In Africa, a non-urban area is affected by hypertension. But in
Burkina Faso, no study on factors associated with awareness, treatment and
control of hypertension has not yet been published. The objectives of this report
are to: (i) identify the factors associated with awareness, treatment, and
control of hypertension in the adult population of Kaya health and demographic
surveillance system (Kaya HDSS) and (ii) estimate health care services
utilization by participant newly screened as hypertensive. METHODS: A screening
survey for hypertension was conducted on 1481 adults in Kaya HDSS in late 2012.
Hypertensive individuals provided information relating to "awareness",
"treatment" and "control" of their hypertension. After approximately two months,
unaware hypertensive individuals were interviewed to know whether they had sought
treatment. RESULTS: During the screening survey, 123 individuals (9.4%) were
identified as having hypertension. Among them, 33 (26.8%, 95% CI: 18.9-34.8) were
aware of their condition, 25 (75.8%, 95% CI: 60.3-91.2) of them were receiving
medication. Among those receiving treatment, 15 (60.0%, 95% CI: 39.4-80.6) had
their blood pressure controlled. Semi-urban residence, presence of chronic
diseases and physical inactivity were significantly associated with awareness of
hypertension. Seventy two of the 90 participants who were classified as unaware
were interviewed two months later. Out of them, 37 individuals had consulted a
health worker and 28 received a diagnosis of hypertension. CONCLUSION: Awareness
was low but treatment and control of those who knew they were hypertensive were
relatively high. These results could be used to improve management of
hypertension in Burkina Faso.
PMID- 25852803
TI - [Epidemiological, clinical and etiological chest pain in outpatient cardiology
consultations Ouagadougou].
PMID- 25852804
TI - Correlates for cardiovascular diseases among diabetic/hypertensive patients
attending outreach clinics in two Nairobi slums, Kenya.
AB - INTRODUCTION: Cardiovascular diseases (CVD) are the leading cause of death in the
world. Over 80% of CVD related deaths occur in low- and middle-income countries
(LMICs). Diabetes and hypertension, whose prevalence in Kenya is on the rise, are
major risk factors for CVD. Despite this, studies indicate that awareness on the
management of risk factors for CVD among diabetic/hypertensive patients in
African populations is generally low. The aim of the study was to determine the
risk factors for CVD among diabetic and/or hypertensive patients attending
diabetes and hypertension management clinics in Korogocho and Viwandani slums of
Nairobi. METHODS: Data were collected using questionnaires administered to 206
diabetic/hypertensive patients attending the clinics between July 2010 and
February 2011. A review of these patients' medical records was done to determine
the history of CVD outcomes such as hypertensive heart diseases, stroke and
peripheral arterial diseases. RESULTS: Majority (66.5%) of the study participants
were females mainly in the 51-65 age category. The study findings revealed that
73 (33.4%) respondents had CVD outcomes. In addition, 41.8% of the respondents
were not aware of the causes of diabetes/hypertension. Age category 51-65 years
had the highest (43.8%) number of respondents with CVD. Sex of the respondents
and awareness of the link between hypertension and CVD were significantly
associated with CVD outcomes (p<0.05) among the respondents. CONCLUSION: Measures
to improve awareness levels among patients at high risk of CVD outcomes are
needed to complement other measures to reduce CVD risk among such patients.
PMID- 25852805
TI - [Upper gastrointestinal endoscopy in 2795 patients at the university campus
hospital of Lome: peculiarities according to sex].
PMID- 25852806
TI - Acceptance of temporal artery thermometry by Nigerian mothers: a comparison with
the traditional methods.
AB - INTRODUCTION: Temporal artery thermometry may be viewed as a suitable alternative
to the traditional thermometry because of its safety and time efficiency.
However, it is yet to gain wide acceptance in African settings because it is
relatively new. The aim of this study was to compare the choices of Nigerian
mothers between the traditional methods (axillary and rectal thermometry) and the
temporal artery thermometry. METHODS: Rectal, axillary and forehead temperatures
were measured in 113 children using rectal and axillary mercury in glass
thermometers and infrared temporal artery thermometer respectively. The
thermometry method preferred by each mother and the reason(s) were documented
using a semi structured questionnaire. The data was analysed using SPSS version
19. RESULTS: The highest number of mothers 44(38.9%) preferred the axillary route
while 42(37.2%) and 27(23.9%) preferred the temporal and rectal routes
respectively. Temporal artery thermometry was the most popular among the mothers
with tertiary education 27(39.7%), whereas axillary thermometry was most
preferred among mothers with primary and secondary education, although this
difference was not statistically significant (chi(2)=0.62,p = 0.96). Mothers
27(33.9%) who preferred rectal thermometry did so because they felt that since
the thermometer is inserted inside the body, it will detect fever better.
CONCLUSION: Nigerian mothers do not have any particular thermometry preference
between the temporal artery thermometry and the traditional methods, so medical
personnel in our environment may resort to any method that is convenient,
accurate, fast and cost effective.
PMID- 25852807
TI - Screening of fetal alcohol syndrome using the T-ACE questionnaire in semi-rural
areas around Lubumbashi: lessons learned.
PMID- 25852808
TI - The assessment of job satisfaction for the healthcare providers in university
clinics of Lubumbashi, Democratic Republic of Congo.
AB - INTRODUCTION: In the world, the health policies are necessary to satisfy with
efficiency the requirements of the quality management in the health sector. The
laboratory of the academic clinics of Lubumbashi in Africa was inspired by the
EFQM model to improve its performance and the quality of its services offered to
the community. The aim of this survey is to evaluate the level of job
satisfaction of the healthcare providers after implementation of the model.
METHODS: Qualitative study used an anonymous questionnaire consisted of 16 semi
directional dichotomous and 12 according to four modality of the Likert's scale;
to evaluate the job satisfaction of the healthcare providers. 40 workers are
concerned and their informed consent is obtained. Epi Info 3.5.3 and SPSS 19.0
software, the Student t test and Chi-square test and the threshold set at p <=
0.05 were used. The mean score was calculated. Cronbach's ' coefficient and
principal component analysis allowed the validity measurement of the
questionnaire, and the correlations has been calculated. RESULTS: This survey had
a rate of answer of 80% on a set of all questionnaires. The Cronbach's
coefficient of reliability is 0.72 on 40 complete observations with 12 questions.
The Kaiser Meyer Olkin (0.564) and the Bartlett test is significant (chi(2)= 57,
30, p=0.001). The Physicians are very dissatisfied (2.363) against the nurses,
and the biologists who are moderately dissatisfied (3 and 3.312). The relative
results to the global satisfaction of the workers show a meaningful difference
between the workers satisfied versus those non satisfied (p = 0.003). More of the
half of the workers is satisfied after the setting up of the EFQM model.
CONCLUSION: A certain number of the factors act together and simultaneously on
the satisfaction of the workers particular in the health sector. The EFQM model
permits the job satisfaction in the hospital because it combines several factors
acting on the individuals.
PMID- 25852809
TI - Yearly Burden of Skin Cancer in Non-Caucasian and Caucasian Solid-organ
Transplant Recipients.
AB - OBJECTIVE: To examine the skin cancer tumor accrual rates in non-Caucasian and
Caucasian post-transplant recipients. DESIGN/SETTING/PARTICIPANTS: Retrospective
chart review of solid-organ transplant patients who presented to the outpatient
dermatology clinic at the University of Chicago and have had at least one skin
biopsy to rule in/out skin cancer in the 10-year period from January 1, 2003, to
December 31, 2012. One hundred fifty-two solid-organ transplant recipients were
identified through a natural language search in CoPathPlus. MEASUREMENTS: Each
transplant patient's skin cancer accrual rates, defined as the number of skin
cancers per person per year, were examined. The average accrual rates for non
Caucasians and Caucasians were compared and analyzed. RESULTS: Of the 152 post
transplant patients identified, 58 were non-Caucasian and 94 were Caucasian.
Eight (13.8%) non-Caucasians developed skin cancer, compared to 61 (64.9%)
Caucasians (P< 0.001). Non-Caucasian post-transplant patients had lower skin
cancer accrual rates with an overall skin cancer accrual rate of 0.13, squamous
cell carcinoma accrual rate of 0.10, and basal cell carcinoma accrual rate of
0.01 versus 1.13 (P< 0.001), 0.96 (P< 0.001), and 0.15 (P< 0.001), respectively,
for Caucasian patients. Comparison of post-transplant non-Caucasian and Caucasian
patients who developed skin cancer revealed lower overall (0.96 vs. 1.74;
P=0.25), squamous cell carcinoma (0.75 vs. 1.49; P=0.16), and basal cell
carcinoma (0.06 vs. 0.24; P=0.13) accrual rates in non-Caucasians. CONCLUSION:
The authors' findings highlight the importance of annual total body skin exams
for post-transplant patients and the need to identify and further educate those
transplant patients with a higher risk for skin cancer development.
PMID- 25852810
TI - Negative predictive value of pigmented lesion evaluation by multispectral digital
skin lesion analysis in a community practice setting.
AB - OBJECTIVE: To determine if the high negative predictive value of a multispectral
digital skin lesion analysis that has been previously found in an academic-based
trial would be similar in a community-based setting with its expected different
distribution of pigmented lesions. DESIGN: Data were collected from patients
undergoing routine skin examinations over a one-year period at a community-based
practice in Florida. All lesions that were selected for biopsy to rule out
melanoma were also imaged with multispectral digital skin lesion analysis prior
to biopsy. Histopathological diagnoses and multispectral digital skin lesion
analysis results were reviewed and compared with findings from a prior primarily
academic center-based multispectral digital skin lesion analysis trial.
SETTING/PARTICIPANTS: Community-based clinical setting in Florida. MEASUREMENTS:
Negative predictive value, sensitivity, and specificity. RESULTS: One hundred
thirty-seven consecutive lesions were selected for biopsy and also analyzed via
multispectral digital skin lesion analysis. All 21 cases with multispectral
digital skin lesion analysis "Low Disorganization" readings were all
histologically benign (100% negative predictive value, 95% lower confidence
boundary = 96.9%). The negative predictive value and the sensitivity were not
significantly different than what was found in the prior academic-based
multispectral digital skin lesion analysis trial. Multispectral digital skin
lesion analysis also correctly identified all high-risk lesions, which were
subsequently confirmed via histology to be one invasive melanoma and 15
moderately dysplastic nevi (100% sensitivity). Specificity with multispectral
digital skin lesion analysis was significantly higher than reported in the
academic-based multispectral digital skin lesion analysis trial (18% vs. 10%,
p=0.02). CONCLUSION: Because of the high negative predictive value achieved by
multispectral digital skin lesion analysis, lesions with readings of "Low
Disorganization" may be considered for observation versus biopsy. Similar to what
was noted in the academic center setting, multispectral digital skin lesion
analysis may help dermatologists reduce the number of unnecessary biopsies while
improving diagnostic accuracy.
PMID- 25852811
TI - Tanning Bed Perception Survey: A Questionnaire-based Study.
AB - OBJECTIVE: This study was intended to investigate the perception of tanning bed
use among college students. DESIGN: A 15-question survey was given to young
adults regarding tanning perceptions. SETTING: Rochester Community College in
Rochester, Minnesota. PARTICIPANTS: Forty-four respondents between 18 and 51
years of age. MEASUREMENTS: Data was collected via a self-reported questionnaire.
RESULTS: In this study, 50 percent of participants were not educated on the risks
of melanoma, and 68 percent were not interested in receiving information on
melanoma and completing a follow-up survey. More specifically, 63 percent versus
89 percent of participants with no tanning bed versus some tanning bed use did
not want information regarding melanoma, respectively. This study also shows that
more tanning bed users believe tanning helps prevent burning than non-tanning bed
users. Fifty-seven percent of the 35 participants who had never used a tanning
bed thought that they never prevent sunburn, while only 11 percent of the nine
participants who had used a tanning bed in the past thought that they never
prevent sunburn, which was statistically significant.
PMID- 25852812
TI - Treatment of Age-related Mid-face Atrophy by Injection of Cohesive Polydensified
Matrix Hyaluronic Acid Volumizer.
AB - OBJECTIVE: Cohesive Polydensified Matrix(r) Hyaluronic Acid Volumizer is designed
to be injected subcutaneously or in deeper soft tissue layers to restore facial
volumes. This post-marketing clinical follow-up was performed to confirm the
safety and effectiveness of the product up to 18 months. DESIGN: Injections were
performed according to standard clinical practice and patients were followed-up
at Months 1, 3, 6, 9, 12, and optionally at Month 18. Effectiveness measures
included facial volume loss scale, global aesthetic improvement scale and
patients' satisfaction. Injection site reactions were recorded to evaluate
safety. RESULTS: Twenty patients with intermediate-to-severe volume loss in the
lateral cheek hollows and/or cheekbone area were treated. Facial volume loss
scale scores dropped significantly from a mean value of 3.1 at baseline to 1.3 at
Day 1. Significant volume enhancement was maintained at each follow-up visit with
mean scores ranging from 1.3 at Month 1 to 1.8 at Month 12. Investigators' global
aesthetic improvement scale assessment showed that up to Month 6 at least 94
percent of patients were rated as "very much improved" or "much improved." At
Month 9, all patients still showed a benefit of treatment with 81 percent rated
as "very much" or "much improved" and 19 percent as "improved." Patients'
evaluation was consistent with investigators' results. A few expected transient
injection site reactions of mild-to-moderate intensity were reported immediately
after treatment. These reactions were considered related to the injection
procedure, rather than the product. CONCLUSION: Cohesive Polydensified Matrix
Hyaluronic Acid Volumizer is safe and effective for mid-face volume augmentation
lasting up to Month 12 and most probably up to Month 18. The aesthetic effect was
demonstrated by the effectiveness evaluations and high patient satisfaction.
PMID- 25852813
TI - Scalp micropigmentation: a concealer for hair and scalp deformities.
AB - BACKGROUND: Cosmetic deformities, resulting from some dermatologic diseases or
deformities caused by hair restoration surgeries, have had few, if any, good,
permanent solutions. Most of these patients have learned to live with their
problems. OBJECTIVE: A cosmetic tattoo technique has been developed to address
unsightly scalp and hair conditions. MATERIALS AND METHODS: The technique called
scalp micropigmentation uses specialized techniques and conventional cosmetic
tattoo instruments and pigments in a stippling pattern on the scalp. RESULTS: A
variety of alopecias, refractory to treatment and hair transplant deformities,
impact millions of men and women. Many of these deformities can be concealed with
scalp micropigmentation, making the deformities minimally detectable. Included
are the results of treatment. Patient satisfaction is very high. CONCLUSION:
Scalp micropigmentation offers a good nonsurgical alternative treatment for hair
and scalp deformities. This paper demonstrates scalp micropigmentation results
and discusses the histology, physiology, and pathology of tattoo pigments in the
skin. The regulation of the tattoo process by the United States Food and Drug
Administration and state governments is summarized. Unlike medical devices, scalp
micropigmentation offers a tattoo-based, non-medical "cover-up" that effectively
hides unsightly conditions on the scalp and creates the illusion of thicker hair.
The authors believe that scalp micropigmentation is destined to become a
standardized offering for physicians specializing in cosmetic office procedures.
PMID- 25852814
TI - Nonalcoholic Fatty liver disease and psoriasis: what a dermatologist needs to
know.
AB - Psoriasis is a systemic inflammatory disease associated with a variety of
comorbidities. It has been shown that psoriasis patients have an increased
incidence of nonalcoholic fatty liver disease over controls. Patients with
nonalcoholic fatty liver disease and psoriasis have more severe skin disease and
are at higher risk of severe liver fibrosis than patients without psoriasis. The
authors will review the diagnosis of nonalcoholic fatty liver disease and also
discuss lifestyle changes and treatments for psoriasis that may benefit or worsen
nonalcoholic fatty liver disease.
PMID- 25852815
TI - Phototherapy-induced Purpuric Eruption in a Neonate.
AB - Phototherapy is commonly utilized in the treatment of neonatal jaundice. The
authors observed a rare cutaneous complication of visible blue light phototherapy
in a neonate with hyperbilirubinemia. A three-day-old neonate was evaluated for a
purpuric rash after initiation of phototherapy for treatment of
hyperbilirubinemia. Cutaneous examination revealed purpuric, nonblanching, well
demarcated lesions on the chest, abdomen, arms, and chin with sparing at shielded
sites. The history, physical examination, and laboratory results support the
diagnosis of purpuric phototherapy-induced eruption. The authors present a case
report of this uncommon cutaneous eruption in a transfused neonate undergoing
phototherapy for treatment of hemolytic disease of the newborn.
PMID- 25852817
TI - Hallmarks of epithelial to mesenchymal transition are detectable in Crohn's
disease associated intestinal fibrosis.
AB - BACKGROUND: Intestinal fibrosis and subsequent stricture formation represent
frequent complications of Crohn's disease (CD). In many organs, fibrosis develops
as a result of epithelial to mesenchymal transition (EMT). Recent studies
suggested that EMT could be involved in intestinal fibrosis as a result of
chronic inflammation. Here, we investigated whether EMT might be involved in
stricture formation in CD patients. METHODS: Human colonic tissue specimens from
fibrotic areas of 18 CD and 10 non-IBD control patients were studied.
Immunohistochemical staining of CD68 (marker for monocytes/macrophages),
transforming growth factor-beta1 (TGFbeta1), beta-catenin, SLUG, E-.cadherin,
alpha-smooth muscle actin and fibroblast activation protein (FAP) were performed
using standard techniques. RESULTS: In fibrotic areas in the intestine of CD
patients, a large number of CD68-positive mononuclear cells was detectable
suggesting an inflammatory character of the fibrosis. We found stronger
expression of TGFbeta1, the most powerful driving force for EMT, in and around
the fibrotic lesions of CD patients than in non-IBD control patients. In CD
patients membrane staining of beta-catenin was generally weaker than in control
patients and more cells featured nuclear staining indicating transcriptionally
active beta-catenin, in fibrotic areas. In these regions we also detected nuclear
localisation of the transcription factor, SLUG, which has also been implicated in
EMT pathogenesis. Adjacent to the fibrotic tissue regions, we observed high
levels of FAP, a marker of reactive fibroblasts. CONCLUSIONS: We demonstrate the
presence of EMT-associated molecules in fibrotic lesions of CD patients. These
findings support the hypothesis that EMT might play a role for the development of
CD-associated intestinal fibrosis.
PMID- 25852816
TI - Intracellular oxidant activity, antioxidant enzyme defense system, and cell
senescence in fibroblasts with trisomy 21.
AB - Down's syndrome (DS) is characterized by a complex phenotype associated with
chronic oxidative stress and mitochondrial dysfunction. Overexpression of genes
on chromosome-21 is thought to underlie the pathogenesis of the major phenotypic
features of DS, such as premature aging. Using cultured fibroblasts with trisomy
21 (T21F), this study aimed to ascertain whether an imbalance exists in
activities, mRNA, and protein expression of the antioxidant enzymes SOD1, SOD2,
glutathione-peroxidase, and catalase during the cell replication process in
vitro. T21F had high SOD1 expression and activity which led to an interenzymatic
imbalance in the antioxidant defense system, accentuated with replicative
senescence. Intracellular ROS production and oxidized protein levels were
significantly higher in T21F compared with control cells; furthermore, a
significant decline in intracellular ATP content was detected in T21F. Cell
senescence was found to appear prematurely in DS cells as shown by SA-beta-Gal
assay and p21 assessment, though not apoptosis, as neither p53 nor the
proapoptotic proteins cytochrome c and caspase 9 were altered in T21F. These
novel findings would point to a deleterious role of oxidatively modified
molecules in early cell senescence of T21F, thereby linking replicative and
stress-induced senescence in cultured cells to premature aging in DS.
PMID- 25852820
TI - Biomarkers of fatigue related to adjuvant chemotherapy for breast cancer:
evaluation of plasma and lymphocyte expression.
AB - BACKGROUND: Fatigue is common in cancer patients receiving adjuvant chemotherapy.
To further understand the mechanism of fatigue and search for potential
biomarkers, we conducted this prospective study. Methods We enrolled breast
cancer (BC) patients before their first adjuvant Adriamycin-based chemotherapy
cycle. Patients responded to the brief fatigue inventory (BFI) and Chalder
fatigue questionnaires and had their blood drawn for both plasma evaluation and
evaluation of the peripheral mononuclear cell fraction (PMNCF) mRNA expression of
various biomarkers. We evaluated FSH, LH, estradiol, DHEA, DHEAS, IL6, IL2,
ILIRA, IL1beta, CRP, Cortisol in the plasma and IL2, IL10, IL6, TGF-beta, KLRC1,
TNF, BTP, SNCA, SOD1, BLNK, PTGS2 and INF gamma expression in the PMNCF. RESULTS:
11 patients did not exhibit an increase in their BFI scores and served as
controls, whereas 32 patients exhibited an increase in their BFI scores compared
with the baseline scores. From the biomarkers we evaluated in the PMNCF, the only
one significantly associated with fatigue was TGF-beta (p = 0.0343), while there
was a trend towards significance with KLRC1 (p = 0.0627). We observed no evidence
of significant associations of any plasma biomarkers with the development of
fatigue. However when we analyzed patients with more severe fatigue, plasma IL1
RA levels correlated directly with higher fatigue scores (p = 0.0136).
CONCLUSIONS: We conclude that fatigue induced by chemotherapy in BC patients is
associated with changes in IL1-ra plasma levels and in TGF-beta lymphocyte
expression. Its mechanism may be different than that observed in long-term BC
survivors or that induced by radiation therapy. TRIAL REGISTRATION: NCT02041364
[ClinicalTrials.gov].
PMID- 25852819
TI - Vaccination in children with allergy to non active vaccine components.
AB - Childhood immunisation is one of the greatest public health successes of the last
century. Vaccines contain an active component (the antigen) which induces the
immune response. They may also contain additional components such as
preservatives, additives, adjuvants and traces of other substances. This review
provides information about risks of hypersensitivity reactions to components of
vaccines. Furthermore, recommendations to avoid or reduce reactions to vaccine
components have been detailed.
PMID- 25852821
TI - Clinical significance of monocyte heterogeneity.
AB - Monocytes are primitive hematopoietic cells that primarily arise from the bone
marrow, circulate in the peripheral blood and give rise to differentiated
macrophages. Over the past two decades, considerable attention to monocyte
diversity and macrophage polarization has provided contextual clues into the role
of myelomonocytic derivatives in human disease. Until recently, human monocytes
were subdivided based on expression of the surface marker CD16. "Classical"
monocytes express surface markers denoted as CD14(++)CD16(-) and account for
greater than 70% of total monocyte count, while "non-classical" monocytes express
the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition
of an intermediate population identified as CD14(++)CD16(+) supports the new
paradigm that monocytes are a true heterogeneous population and careful
identification of specific subpopulations is necessary for understanding monocyte
function in human disease. Comparative studies of monocytes in mice have yielded
more dichotomous results based on expression of the Ly6C antigen. In this review,
we will discuss the use of monocyte subpopulations as biomarkers of human disease
and summarize correlative studies in mice that may yield significant insight into
the contribution of each subset to disease pathogenesis.
PMID- 25852818
TI - The significance of macrophage polarization subtypes for animal models of tissue
fibrosis and human fibrotic diseases.
AB - The systemic and organ-specific human fibrotic disorders collectively represent
one of the most serious health problems world-wide causing a large proportion of
the total world population mortality. The molecular pathways involved in their
pathogenesis are complex and despite intensive investigations have not been fully
elucidated. Whereas chronic inflammatory cell infiltration is universally present
in fibrotic lesions, the central role of monocytes and macrophages as regulators
of inflammation and fibrosis has only recently become apparent. However, the
precise mechanisms involved in the contribution of monocytes/macrophages to the
initiation, establishment, or progression of the fibrotic process remain largely
unknown. Several monocyte and macrophage subpopulations have been identified,
with certain phenotypes promoting inflammation whereas others display profibrotic
effects. Given the unmet need for effective treatments for fibroproliferative
diseases and the crucial regulatory role of monocyte/macrophage subpopulations in
fibrogenesis, the development of therapeutic strategies that target specific
monocyte/macrophage subpopulations has become increasingly attractive. We will
provide here an overview of the current understanding of the role of
monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis
and in various systemic and organ-specific human fibrotic diseases. Furthermore,
we will discuss recent approaches to the design of effective anti-fibrotic
therapeutic interventions by targeting the phenotypic differences identified
between the various monocyte and macrophage subpopulations.
PMID- 25852824
TI - A reply to the commentary on "Animal models of chronic tympanic membrane
perforation: in response to plasminogen initiates and potentiates the healing of
acute and chronic tympanic membrane perforations in mice" by Wang AY, Shen Y,
Wang JT, Eikelboom RH and Dilley RJ; Clin Translat Med, 2014; 3:5.
PMID- 25852822
TI - EMT and tumor metastasis.
AB - EMT and MET comprise the processes by which cells transit between epithelial and
mesenchymal states, and they play integral roles in both normal development and
cancer metastasis. This article reviews these processes and the molecular
pathways that contribute to them. First, we compare embryogenesis and development
with cancer metastasis. We then discuss the signaling pathways and the
differential expression and down-regulation of receptors in both tumor cells and
stromal cells, which play a role in EMT and metastasis. We further delve into the
clinical implications of EMT and MET in several types of tumors, and lastly, we
discuss the role of epigenetic events that regulate EMT/MET processes. We
hypothesize that reversible epigenetic events regulate both EMT and MET, and
thus, also regulate the development of different types of metastatic cancers.
PMID- 25852823
TI - Understanding the MIND phenotype: macrophage/microglia inflammation in
neurocognitive disorders related to human immunodeficiency virus infection.
AB - Tissue macrophages play important roles in maintaining homeostasis in most organs
of the body including the brain where microglia represent the resident phagocytic
cells of this compartment. The possibility of one day harnessing macrophage
plasticity to treat or ameliorate disorders including obesity, cancer, organ
damage, intestinal disorders, neurodegeneration, and cardiovascular disease in
which these cells play a role, is a very exciting prospect. Inflammatory
signaling is required for regenerative repair, healing, and pathogen clearance
functions. However, when the inflammatory response persists in a chronic fashion
over an extended period of time, damage to neurons is followed by neuronal injury
and dysfunction. Macrophages in the brain are heterogeneous arising from tissues
during embryogenesis, and in the adult, from bone marrow derived monocytes that
enter through the blood-brain-barrier. While much of our insight regarding
macrophage functional subtypes has been garnered through elegant studies in mice,
which are amenable to genetic manipulation, far less is known about such cells in
human tissues, and particularly in the brain under normal, disease, or injurious
conditions. In this regard, non-human primate models for human immunodeficiency
virus have been extremely useful for understanding the contribution of bone
marrow-derived monocytes in neurological disease and their interaction and impact
on the activation state of resident microglia in the brain. This review will
focus on what has been learned from the rhesus macaque models about the types of
macrophages present in the brains of animals with encephalitis. In vitro studies,
which have used human blood monocytes differentiated into macrophages to address
the question of macrophage subsets in HIV infection will be highlighted. Recent
insights on macrophage phenotype and persistent inflammation in the brain in HIV
associated neurocognitive disorder from immunohistochemical studies on human
autopsy tissue will be examined.
PMID- 25852826
TI - MELK-a conserved kinase: functions, signaling, cancer, and controversy.
AB - Maternal embryonic leucine zipper kinase (MELK) is a highly conserved
serine/threonine kinase initially found to be expressed in a wide range of early
embryonic cellular stages, and as a result has been implicated in embryogenesis
and cell cycle control. Recent evidence has identified a broader spectrum of
tissue expression pattern for this kinase than previously appreciated. MELK is
expressed in several human cancers and stem cell populations. Unique spatial and
temporal patterns of expression within these tissues suggest that MELK plays a
prominent role in cell cycle control, cell proliferation, apoptosis, cell
migration, cell renewal, embryogenesis, oncogenesis, and cancer treatment
resistance and recurrence. These findings have important implications for our
understanding of development, disease, and cancer therapeutics. Furthermore
understanding MELK signaling may elucidate an added dimension of stem cell
control.
PMID- 25852825
TI - An engineered micropattern to reduce bacterial colonization, platelet adhesion
and fibrin sheath formation for improved biocompatibility of central venous
catheters.
AB - BACKGROUND: Catheter-related bloodstream infections (CRBSIs) and catheter-related
thrombosis (CRT) are common complications of central venous catheters (CVC),
which are used to monitor patient health and deliver medications. CVCs are
subject to protein adsorption and platelet adhesion as well as colonization by
the natural skin flora (i.e. Staphylococcus aureus and Staphylococcus
epidermidis). Antimicrobial and antithrombotic drugs can prevent infections and
thrombosis-related complications, but have associated resistance and safety
risks. Surface topographies have shown promise in limiting platelet and bacterial
adhesion, so it was hypothesized that an engineered Sharklet micropattern,
inspired by shark-skin, may provide a combined approach as it has wide reaching
anti-fouling capabilities. To assess the feasibility for this micropattern to
improve CVC-related healthcare outcomes, bacterial colonization and platelet
interactions were analyzed in vitro on a material common for vascular access
devices. METHODS: To evaluate bacterial inhibition after simulated vascular
exposure, micropatterned thermoplastic polyurethane surfaces were preconditioned
with blood proteins in vitro then subjected to a bacterial challenge for 1 and 18
h. Platelet adhesion was assessed with fluorescent microscopy after incubation of
the surfaces with platelet-rich plasma (PRP) supplemented with calcium. Platelet
activation was further assessed by monitoring fibrin formation with fluorescent
microscopy after exposure of the surfaces to platelet-rich plasma (PRP)
supplemented with calcium in a flow-cell. Results are reported as percent
reductions and significance is based on t-tests and ANOVA models of log
reductions. All experiments were replicated at least three times. RESULTS: Blood
and serum conditioned micropatterned surfaces reduced 18 h S. aureus and S.
epidermidis colonization by 70% (p <= 0.05) and 71% (p < 0.01), respectively,
when compared to preconditioned unpatterned controls. Additionally, platelet
adhesion and fibrin sheath formation were reduced by 86% and 80% (p < 0.05),
respectively, on the micropattern, when compared to controls. CONCLUSIONS: The
Sharklet micropattern, in a CVC-relevant thermoplastic polyurethane,
significantly reduced bacterial colonization and relevant platelet interactions
after simulated vascular exposure. These results suggest that the incorporation
of the Sharklet micropattern on the surface of a CVC may inhibit the initial
events that lead to CRBSI and CRT.
PMID- 25852827
TI - Neuropathic caner pain: is it linked to the recurrence of cancer?
PMID- 25852828
TI - What is the Role of Epidural Injections in the Treatment of Lumbar Discogenic
Pain: A Systematic Review of Comparative Analysis with Fusion.
AB - BACKGROUND: Lumbar discogenic pain without pain mediated by a disc herniation,
facet joints, or the sacroiliac joints, is common and often results in chronic,
persistent pain and disability. After conservative treatment failure, injection
therapy, such as an epidural injection, is frequently the next step considered in
managing discogenic pain. The objective of this systematic review is to determine
the efficacy of lumbar epidural injections in managing discogenic pain without
radiculopathy, and compare this approach to lumbar fusion or disc arthroplasty
surgery. METHODS: A systematic review of randomized trials published from 1966
through October 2014 of all types of epidural injections and lumbar fusion or
disc arthroplasty in managing lumbar discogenic pain was performed with
methodological quality assessment and grading of evidence. The level of evidence
was based on the grading of evidence criteria which, was conducted using 5 levels
of evidence ranging from levels I to V. RESULTS: Based on a qualitative
assessment of the evidence for both approaches, there is Level II evidence for
epidural injections, either caudal or lumbar interlaminar. CONCLUSIONS: The
available evidence suggests fluoroscopically directed epidural injections provide
long-term improvement in back and lower extremity pain for patients with lumbar
discogenic pain. There is also limited evidence showing the potential
effectiveness of surgical interventions compared to nonsurgical treatments.
PMID- 25852829
TI - Reducing Irrational Beliefs and Pain Severity in Patients Suffering from Non
Cardiac Chest Pain (NCCP): A Comparison of Relaxation Training and Metaphor
Therapy.
AB - BACKGROUND: Patients suffering from non-cardiac chest pain (NCCP) can interpret
their chest pain wrongly despite having received a correct diagnosis. The
objective of this study was to compare the efficacy of the relaxation method with
metaphor therapy for reducing irrational beliefs and pain severity in patients
with NCCP. METHODS: Using a randomized controlled trial, 33 participants were
randomly divided into a relaxation training group (n= 13), a metaphor therapy
group (n = 10), and a control group (n = 10), and were studied for 4 weeks. The
two tools used in this research were the Brief Pain Inventory (BPI) index for
determining the degree of pain and the short version of the Jones Irrational
Belief Test. Metaphor therapy and a relaxation technique based on Ost's treatment
were used as the interventions. The collected data were analyzed with a
multivariate analysis of covariance (MANCOVA), a Chi-square test, and the
Bonferroni procedure of post-hoc analysis. RESULTS: The relaxation training
method was significantly more effective than both metaphor therapy and the lack
of treatment in reducing the patients' beliefs of hopelessness in the face of
changes and emotional irresponsibility, as well as the pain severity. Metaphor
therapy was not effective on any of these factors. In fact, the results did not
support the effectiveness of metaphor therapy. CONCLUSIONS: Regarding the
effectiveness of the relaxation method as compared with metaphor therapy and the
lack of treatment in the control group, this study suggests that relaxation
should be paid greater attention as a method for improving the status of
patients. In addition, more studies are needed to determine the effectiveness of
metaphor therapy in this area.
PMID- 25852830
TI - Anti-allodynic Efficacy of NMDA Antagonist Peptide and Noradrenaline Alone and in
Combination in Rodent Neuropathic Pain Model.
AB - BACKGROUND: The present experiment was conducted to identify the cooperative
effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral
neuropathic pain. METHODS: Chronic constriction injury of the right sciatic nerve
was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was
inserted into the subarachnoid space. Acetone drops and a 44C water bath were
used to evaluate the cold and heat allodynia, respectively. Placing and grasping
reflexes were used to assess the locomotor system. RESULTS: SHG at 0.5 and 1 ug
significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was
also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and 1 ug
(P < 0.001) of SHG. 1 ug of noradrenaline, but not 0.5 ug, significantly
alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating
effect of noradrenaline or SHG disappeared when the two compounds were
administrated in equal concentrations. A significant difference (P < 0.01 in the
acetone and P < 0.05 in the heat) was observed in the groups under equal doses of
the two compounds, with a lower effectiveness of the combination therapy.
CONCLUSIONS: Our findings suggest that the simultaneous administrations of
noradrenaline and SHG do not result in synergistic analgesia, and combination
therapy may not be a good approach to the treatment of chronic neuropathic pain
syndrome.
PMID- 25852831
TI - Detection Rate of Intravascular Injections during Cervical Medial Branch Blocks:
A Comparison of Digital Subtraction Angiography and Static Images from
Conventional Fluoroscopy.
AB - BACKGROUND: The most definitive diagnosis of neck pain caused by facet joints can
be obtained through cervical medial branch blocks (CMBBs). However, intravascular
injections need to be carefully monitored, as they can increase the risk of false
negative blocks when diagnosing cervical facet joint syndrome. In addition,
intravascular injections can cause neurologic deficits such as spinal infarction
or cerebral infarction. Digital subtraction angiography (DSA) is a radiological
technique that can be used to clearly visualize the blood vessels from
surrounding bones or dense soft tissues. The purpose of this study was to compare
the rate of detection of intravascular injections during CMBBs using DSA and
static images obtained through conventional fluoroscopy. METHODS: Seventy-two
patients were included, and a total of 178 CMBBs were performed. The respective
incidences of intravascular injections during CMBBs using DSA and static images
from conventional fluoroscopy were measured. RESULTS: A total of 178 CMBBs were
performed on 72 patients. All cases of intravascular injections evidenced by the
static images were detected by the DSAs. The detection rate of intravascular
injections was higher from DSA images than from static images (10.7% vs. 1.7%, P
< 0.001). CONCLUSIONS: According to these findings, the use of DSA can improve
the detection rate of intravascular injections during CMBBs. The use of DSA may
therefore lead to an increase in the diagnostic and therapeutic value of CMBBs.
In addition, it can decrease the incidence of potential side effects during
CMBBs.
PMID- 25852832
TI - Alternative Method of Retrocrural Approach during Celiac Plexus Block Using a
Bent Tip Needle.
AB - BACKGROUND: This study sought to determine safe ranges of oblique angle, skin
entry point and needle length by reviewing computed tomography (CT) scans and to
evaluate the usefulness of a bent tip needle during celiac plexus block (CPB).
METHODS: CT scans of 60 CPB patients were reviewed. Image of the uppermost margin
of L2 vertebral body was used to measure the minimal and maximal oblique angles
and the distances from the midline to skin puncture point. The imaginary needle
trajectory distance was calculated by three-dimensional measurement. When the
procedure was performed by using a 10 degrees bent tip needle under a 20 degrees
oblique X-ray fluoroscopic view, the distance (GF/G'F) from the midline to the
actual puncture site was measured. RESULTS: The imaginary safe oblique angle
range was 26.4-34.2 degrees and 27.7-36.0 degrees on the right and left,
respectively. The distance from the midline to skin puncture point was 6.1-7.6 cm
on the right and 6.3-7.6 cm on the left. The needle trajectory distance at
minimal angle was 9.6-11.6 cm on the right and 9.5-11.5 cm on the left. The
distance of GF/G'F was 5.1-6.5 cm and 5.0-6.4 cm on the right and left,
respectively. All imaginary parameters were correlated with BMI except for
GF/G'F. All complications were mild and transient. CONCLUSIONS: We identified
safe values of angles and distances using a straight needle. Furthermore, using a
bent tip needle under a 20 degrees oblique fluoroscopic view, we could safely
perform CPB with smaller parameter values.
PMID- 25852833
TI - Persistent Post-radiotherapy Pain and Locoregional Recurrence in Head and Neck
Cancer-Is There a Hidden Link?
AB - BACKGROUND: To explore the relationship between persistent post-radiotherapy pain
and locoregional recurrence in head and neck cancer patients. METHODS: Five year
retrospective data was reviewed of 86 patients of head and neck cancer treated
with radiotherapy who continued to have pain at 6 weeks after completion of
treatment. At follow-up after 3 months, these patients were stratified into:
Group A (n = 39) constituted of patients whose pain subsided and Group B (n = 47)
were patients who continued to have persistent pain. RESULTS: At median follow-up
time of 25 months (range: 8-47), one patient (2.6%) and 18 (38.3%) patients in
group A and group B had locoregional recurrence respectively (P < 0.0001).
Furthermore, group B patients had higher mean pain score levels as compared to
group A (P = 0.03). Patients in whom pain subsided within 3 months had
statistically much greater disease-free survival in comparison to those with
persistent pain (P < 0.0001). CONCLUSIONS: Pain in head and neck cancer is an
important symptom and should be considered a poor prognostic factor. In the
current study, the majority of the patients with persistent pain had recurrent
disease as compared to those in whom pain subsided within 3 months of post
treatment. It is suggested that patients with persistent pain need more intense
follow-up and should be investigated thoroughly to detect recurrence at an early
stage to provide a better quality of life.
PMID- 25852834
TI - A Comparison of Two Techniques for Ultrasound-guided Caudal Injection: The
Influence of the Depth of the Inserted Needle on Caudal Block.
AB - BACKGROUND: Caudal epidural injections have been commonly performed in patients
with low back pain and radiculopathy. Although caudal injection has generally
been accepted as a safe procedure, serious complications such as inadvertent
intravascular injection and dural puncture can occur. The present prospective
study was designed to investigate the influence of the depth of the inserted
needle on the success rate of caudal epidural blocks. METHODS: A total of 49
adults scheduled to receive caudal epidural injections were randomly divided into
2 groups: Group 1 to receive the caudal injection through a conventional method,
i.e., caudal injection after advancement of the needle 1 cm into the sacral canal
(n = 25), and Group 2 to receive the injection through a new method, i.e.,
injection right after penetrating the sacrococcygeal ligament (n = 24).
Ultrasound was used to identify the sacral hiatus and to achieve accurate needle
placement according to the allocated groups. Contrast dyed fluoroscopy was
obtained to evaluate the epidural spread of injected materials and to monitor the
possible complications. RESULTS: The success rates of the caudal injections were
68.0% in Group 1 and 95.8% in Group 2 (P = 0.023). The incidences of
intravascular injections were 24.0% in Group 1 and 0% in Group 2 (P = 0.022). No
intrathecal injection was found in either of the two groups. CONCLUSIONS: The new
caudal epidural injection technique tested in this study is a reliable
alternative, with a higher success rate and lower risk of accidental
intravascular injection than the conventional technique.
PMID- 25852835
TI - Evaluation of pain and its effect on quality of life and functioning in men with
spinal cord injury.
AB - BACKGROUND: Pain is one of the most important consequences of spinal cord injury
(SCI). It may affect several aspects of life, especially the quality of life
(QoL). Hence, this study was conducted to establish an understanding of pain and
its correlates and effects on patients with SCI in our community. METHODS: In a
cross-sectional study, 58 male veterans suffering from SCI were admitted to our
center for a regular follow-up. Demographic and SCI-related descriptive
information were gathered using a self-reported questionnaire. To evaluate the
patients' pain quality and the effect of pain on daily life, a questionnaire in 3
parts of lumbar, cervical and shoulder pain was administered. EuroQoL
questionnaire and General Health Questionnaire (GHQ) 12 were also used to assess
the patients' QoL. RESULTS: The mean age of the participants was 45.91 +/- 6.69
with mean injury time of 25.54 +/- 5.91. forty-four patients (75.9%) reported
pain, including lumbar pain (63%), cervical pain (39%) and shoulder pain (51%).
The presence of pain was associated with lower QoL. Patients with lumbar pain
reported a significant amount of pain affecting their daily life and this effect
was higher in patients with lower GHQ score or anxiety/depressive disorder.
CONCLUSIONS: Musculoskeletal pain, is a common complaint in veterans with SCI and
is inversely associated with functioning and general health status. Lumbar and
shoulder pain affects patient's daily living more than cervical pain.
PMID- 25852836
TI - Risk factors associated with clinical insomnia in chronic low back pain: a
retrospective analysis in a university hospital in Korea.
AB - BACKGROUND: Insomnia is becoming increasingly recognized as a clinically
important symptom in patients with chronic low back pain (CLBP). In this
retrospective study, we have determined risk factors associated with clinical
insomnia in CLBP patients in a university hospital in Korea. METHODS: Data from
four-hundred and eighty one CLBP patients was analyzed in this study. The
Insomnia Severity Index (ISI) was used to determine the presence of clinical
insomnia (ISI score >= 15). Patients' demographics and pain-related factors were
evaluated by logistic regression analysis to identify risk factors of clinical
insomnia in CLBP. RESULTS: It was found that 43% of patients reported mild to
severe insomnia after the development of back pain. In addition, 20% of patients
met the criteria for clinically significant insomnia (ISI score >= 15). In a
stepwise multivariate analysis, high pain intensity, the presence of comorbid
musculoskeletal pain and neuropathic pain components, and high level of
depression were strongly associated with clinical insomnia in CLBP. Among these
factors, the presence of comorbid musculoskeletal pain other than back pain was
the strongest determinant, with the highest odds ratio of 8.074 (95% CI 4.250 to
15.339) for predicting clinical insomnia. CONCLUSIONS: Insomnia should be
addressed as an integral part of pain management in CLBP patients with these risk
factors, especially in patients suffering from CLBP with comorbid musculoskeletal
pain.
PMID- 25852837
TI - Acute motor weakness of opposite lower extremity after percutaneous epidural
neuroplasty.
AB - Recently, percutaneous epidural neuroplasty has become widely used to treat
radicular pain caused by spinal stenosis or a herniated intervertebral disc. A 19
year-old female patient suffering from left radicular pain caused by an L4-L5
intervertebral disc herniation underwent percutaneous epidural neuroplasty of the
left L5 nerve root using a Racz catheter. After the procedure, the patient
complained of acute motor weakness in the right lower leg, on the opposite site
to where the neuroplasty was conducted. Emergency surgery was performed, and
swelling of the right L5 nerve root was discovered. The patient recovered her
motor and sensory functions immediately after the surgery. Theoretically, the
injection of a large volume of fluid in a patient with severe spinal stenosis
during epidural neuroplasty can increase the pressure on the opposite side of the
epidural space, which may cause injury of the opposite nerve by barotrauma from a
closed compartment. Practitioners should be aware of this potential complication.
PMID- 25852838
TI - Paraplegia following intercostal nerve neurolysis with alcohol and thoracic
epidural injection in lung cancer patient.
AB - The goal of cancer treatment is generally pain reduction and function recovery.
However, drug therapy does not treat pain adequately in approximately 43% of
patients, and the latter may have to undergo a nerve block or neurolysis. In the
case reported here, a 42-year-old female patient with lung cancer
(adenocarcinoma) developed paraplegia after receiving T8-10 and 11(th)
intercostal nerve neurolysis and T9-10 interlaminar epidural steroid injections.
An MRI results revealed extensive swelling of the spinal cord between the T4
spinal cord and conus medullaris, and T5, 7-11, and L1 bone metastasis. Although
steroid therapy was administered, the paraplegia did not improve.
PMID- 25852839
TI - Delayed allergic reaction to secondary administrated epidural hyaluronidase.
AB - We are reporting a rare case of a delayed hypersensitivity reaction caused by
hyaluronidase allergy following a lumbar transforaminal epidural block. Using an
intradermal skin test, we have provided evidence that the systemic allergic
reaction resulted from hypersensitivity to hyaluronidase. To our knowledge, this
is a rare case of a delayed hypersensitivity reaction to epidural hyaluronidase,
comprised of an initial exposure to hyaluronidase with no subsequent allergic
response in prior block followed by a subsequent delayed reaction to
hyaluronidase during a second epidural block.
PMID- 25852840
TI - Combined use of intrathecal opioids and dexmedetomidine in the management of
neuropathic pain.
PMID- 25852841
TI - An update on the management of diabetic neuropathic pain: a few comments.
PMID- 25852842
TI - Bedside ultrasound training using web-based e-learning and simulation early in
the curriculum of residents.
AB - BACKGROUND: Focused bedside ultrasound is rapidly becoming a standard of care to
decrease the risks of complications related to invasive procedures. The purpose
of this study was to assess whether adding to the curriculum of junior residents
an educational intervention combining web-based e-learning and hands-on training
would improve the residents' proficiency in different clinical applications of
bedside ultrasound as compared to using the traditional apprenticeship teaching
method alone. METHODS: Junior residents (n = 39) were provided with two
educational interventions (vascular and pleural ultrasound). Each intervention
consisted of a combination of web-based e-learning and bedside hands-on training.
Senior residents (n = 15) were the traditionally trained group and were not
provided with the educational interventions. RESULTS: After the educational
intervention, performance of the junior residents on the practical tests was
superior to that of the senior residents. This was true for the vascular
assessment (94% +/- 5% vs. 68% +/- 15%, unpaired student t test: p < 0.0001, mean
difference: 26 (95% CI: 20 to 31)) and even more significant for the pleural
assessment (92% +/- 9% vs. 57% +/- 25%, unpaired student t test: p < 0.0001, mean
difference: 35 (95% CI: 23 to 44)). The junior residents also had a significantly
higher success rate in performing ultrasound-guided needle insertion compared to
the senior residents for both the transverse (95% vs. 60%, Fisher's exact test p
= 0.0048) and longitudinal views (100% vs. 73%, Fisher's exact test p = 0.0055).
CONCLUSIONS: Our study demonstrated that a structured curriculum combining web
based education, hands-on training, and simulation integrated early in the
training of the junior residents can lead to better proficiency in performing
ultrasound-guided techniques compared to the traditional apprenticeship model.
PMID- 25852843
TI - Case report: an unrecognized etiology of transient gallbladder pain in heart
failure diagnosed with internist-performed point-of-care ultrasound.
AB - The excellent sensitivity and specificity of right upper quadrant (RUQ)
ultrasound for gallbladder pathology in patients with abdominal pain is heavily
relied upon in routine diagnostic evaluation. The hour-to-hour timing of this
test in a patient with fluctuating symptoms is not widely recognized as having a
significant impact on its sensitivity. However, we present a case report
describing the essential role of symptom-timed point-of-care ultrasound in making
an elusive diagnosis of transient cholecystalgia in a patient with RUQ pain and
congestive heart failure (CHF). This case also demonstrates an important etiology
of RUQ pain in patients with CHF beyond that of congestive hepatopathy. A review
of the related entities of acalculous cholecystitis, congestive hepatopathy, and
diffuse gallbladder wall thickening is provided.
PMID- 25852844
TI - A rare cause of acquired immune deficiency syndrome related pancytopenia.
AB - A 21-year-old male with acquired immune deficiency syndrome, not on highly active
antiretroviral treatment (HAART) was admitted after complaining of headache and
intermittent diarrhea, found to have Cryptococcal meningitis. During the course
of his hospitalization, patient developed pancytopenia. Anemia panel, serologies
including Epstein barr virus, cytomegalovirus, and parvovirus were negative.
Patient then developed high grade fever with elevated liver enzymes. Blood
cultures, urine cultures, stool cultures, and repeat cerebrospinal fluid cultures
remained negative. Patient subsequently developed skin lesions which on biopsy
showed Kaposi's sarcoma, and upon endoscopy, noted to have gastrointestinal
Kaposi's sarcoma involvement. Human herpes virus 8 was positive. Bone marrow
biopsy revealed hemophagocytic lymphohistiocytosis. Despite having a concern for
patient developing immune reconstitution syndrome which may worsen his
meningitis, HAART was initiated and patient's symptoms improved including
resolution of fevers and hematological as well as liver abnormalities. Kaposi's
sarcoma improved as well.
PMID- 25852845
TI - Interferon alpha Therapy in Patients with Chronic Hepatitis C Infection: Quality
of Life and Depression.
AB - Health-related quality of life was examined in 49 patients with hepatitis C virus
with no psychiatric history who received interferon (IFN)-alpha treatment.
Quality of life was assessed at baseline, at 3-time points during IFN-alpha
therapy and at 1-6 month follow-up, using SF-36. Hepatitis C virus patients
showed poorer physical functioning and better social and mental functioning than
a normal population. Significant decreases from baseline SF-36 scores were
observed at an early phase of treatment. Six patients developed major depression
during IFN-alpha treatment. At baseline, they had reported more bodily pain than
patients who did not develop depression during treatment. Planned contrasts
revealed that worsening in some dimensions of quality of life at 2 months was
greater in depressed than in non-depressed patients. Results suggest that
depressive symptoms should be accurately monitored during IFN-alpha therapy even
in patients with no psychiatric history, especially if they present with bodily
pain.
PMID- 25852846
TI - Acute iatrogenic polycythemia induced by massive red blood cell transfusion
during subtotal abdominal colectomy.
AB - A 46 year old man was transfused ten units of packed red blood cells during
subtotal colectomy after intraoperative point-of-care testing values demonstrated
hemoglobin values less than seven grams per deciliter (g/dL). A postoperative
hemoglobin analyzed in a standard hematologic laboratory revealed a hemoglobin
value of 27.8 g/dL. He underwent emergent red blood cell depletion therapy which
decreased his hemoglobin to 7.5 g/dL. The physiologic consequences of iatrogenic
polycythemia caused by massive transfusion during major abdominal surgery must
take into account the fluid shifts that interplay between the osmotic load,
viscosity of blood, and postoperative third spacing of fluid. Treatment of acute
iatrogenic polycythemia can be effectively accomplished by red blood cell
depletion therapy. However, fluid shifts caused by massive transfusion followed
by rapid red cell depletion produce a unique physiologic state that is without a
well-described algorithm for management.
PMID- 25852847
TI - Emergency management of major bleeding in a case of maxillofacial trauma and
anticoagulation: utility of prothrombin complex concentrates in the shock room.
AB - Life-threatening bleeding in anticoagulation with Warfarin is an emergency
challenging issue. Several approaches are available to treat bleeding in either
over-anticoagulation or proper-anticoagulation, including vitamin K, fresh frozen
plasma and prothrombin complex concentrates (PCC) administration. In coexisting
trauma-induced bleeding and anticoagulation, reversal of anticoagulation must be
a rapid and highly effective procedure. Furthermore the appropriate treatment
must be directly available in each shock rooms to guarantee the rapid management
of the emergency. PCC require a simple storage, rapid accessibility, fast
administration procedures and high effectiveness. Here we report the utility of
PCC in management of a craniofacial trauma in proper-anticoagulation.
PMID- 25852848
TI - Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor
agonist responsive patients with primary immune thrombocytopenia: an
observational retrospective report in real life clinical practice.
AB - Thrombopoietin mimetics are new treatment options for patients with immune throm
bocytopenia (ITP). Because of their mechanism of action, long-term administration
was envisioned in order to maintain effective thrombopoiesis. We report on 30
romiplostim treated patients: 13/27 responders (48%) achieved stable platelet
counts on a mean romiplostim dose of 2.43 ug/kg and were able to stop romiplostim
after a mean of 44.3 weeks (range 12-122) on therapy with sustained response
maintained at a mean of 26 months (range 12-52). No bleeding events occurred
during the observational period. No specific patient's features nor pattern of
early response seemed to predict for sustained response. However, patients
achieving safe platelet counts at lower dosages are probably worth a try of
therapy tapering and discontinuation. Our observations support feasibility of
romiplostim safe suspension in a relevant proportion of ITP patients.
PMID- 25852849
TI - Complex karyotype with novel translocation in pure erythroid leukemia patient.
AB - Pure erythroid leukemia (PEL) is rare hematopoietic neoplasm characterized by
uncontrolled proliferation of immature erythroid precursors - mainly abnormal
proery-throblasts - comprising at least 80% of bone marrow cells. In this paper,
I present a case of 48 years old patient, who presented with pancytopenia and
circulating erythroblast in peripheral blood after long history of alcohol abuse.
Bone marrow examination revealed hypercellular marrow which is markedly
infiltrated with immature erythroid precursors. An expanded panel of
immunophenotyping markers has confirmed the diagnosis of PEL. Cytogenetics
analysis detected a complex karyotype with multiple chromosomal abnormalities and
a novel translocation, t(8;9) (p11.2;q12), which has not been reported in acute
myeloid leukemia (AML) in the past. The patient was treated with standard AML
chemotherapy but he did not show an optimal response and passed away. An updated
and short review about various aspects of PEL has been made with special focus on
immunophenotyping and genetic studies.
PMID- 25852850
TI - Central neurotoxicity of immunomodulatory drugs in multiple myeloma.
AB - Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple
myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common
side effects of thalidomide is neurotoxicity, predominantly in the form of
peripheral neuropathy. We report 6 cases of significant central neurotoxicity
associated with IMiD therapy. Treatment with thalidomide (1 patient),
lenalidomide (4 patients), and pomalidomide (1 patient) was associated with
various clinical manifestations of central neurotoxicity, including reversible
coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should
be recognized as an important side effect of IMiD therapy.
PMID- 25852851
TI - Pulmonary extramedullary hematopoiesis involving the pulmonary artery.
AB - Extramedullary hematopoiesis (EMH) occurs as a complication of hematologic
disorders such as myelofibrosis, sickle cell anemia and thalassemia. The
extramedullary tissue usually involves liver, spleen and lymph nodes, less
frequently the chest. We present a recent case of a man with myeloproliferative
neoplasm who developed pulmonary hemorrhage secondary to EMH in the lung and
pulmonary artery. Radiation therapy was considered the best approach, but it
didn't work and the patient died a week after radiation therapy was completed. We
also review herein the present literature.
PMID- 25852852
TI - CLO: The cell line ontology.
AB - BACKGROUND: Cell lines have been widely used in biomedical research. The
community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library
that covers the domain of cell lines. Since its publication two years ago,
significant updates have been made, including new groups joining the CLO
consortium, new cell line cells, upper level alignment with the Cell Ontology
(CL) and the Ontology for Biomedical Investigation, and logical extensions.
CONSTRUCTION AND CONTENT: Collaboration among the CLO, CL, and OBI has
established consensus definitions of cell line-specific terms such as 'cell
line', 'cell line cell', 'cell line culturing', and 'mortal' vs. 'immortal cell
line cell'. A cell line is a genetically stable cultured cell population that
contains individual cell line cells. The hierarchical structure of the CLO is
built based on the hierarchy of the in vivo cell types defined in CL and tissue
types (from which cell line cells are derived) defined in the UBERON cross
species anatomy ontology. The new hierarchical structure makes it easier to
browse, query, and perform automated classification. We have recently added
classes representing more than 2,000 cell line cells from the RIKEN BRC Cell Bank
to CLO. Overall, the CLO now contains ~38,000 classes of specific cell line cells
derived from over 200 in vivo cell types from various organisms. UTILITY AND
DISCUSSION: The CLO has been applied to different biomedical research studies.
Example case studies include annotation and analysis of EBI ArrayExpress data,
bioassays, and host-vaccine/pathogen interaction. CLO's utility goes beyond a
catalogue of cell line types. The alignment of the CLO with related ontologies
combined with the use of ontological reasoners will support sophisticated
inferencing to advance translational informatics development.
PMID- 25852854
TI - Rodent models of osteoporosis.
AB - The aim of this protocol is to provide a detailed description of male and female
rodent models of osteoporosis. In addition to indications on the methods of
performing the surgical procedures, the choice of reliable and safe anaesthetics
is also described. Post-operative care, including analgesia administration for
pain management, is also discussed. Ovariectomy in rodents is a procedure where
ovaries are surgically excised. Hormonal changes resulting from ovary removal
lead to an oestrogen-deprived state, which enhances bone remodelling, causes bone
loss and increases bone fracture risk. Therefore, ovariectomy has been considered
as the most common preclinical model for understanding the pathophysiology of
menopause-associated events and for developing new treatment strategies for
tackling post-menopausal osteoporosis. This protocol also provides a detailed
description of orchidectomy, a model for androgen-deficient osteoporosis in
rodents. Endocrine changes following testes removal lead to hypogonadism, which
results in accelerated bone loss, increasing osteoporosis risk. Orchidectomised
rodent models have been proposed to mimic male osteoporosis and therefore remain
a valuable tool for understanding androgen deficiency in aged men. Although it
would have been particularly difficult to assemble an internationally acceptable
description of surgical procedures, here we have attempted to provide a
comprehensive guide for best practice in performing ovariectomy and orchidectomy
in laboratory rodents. Research scientists are reminded that they should follow
their own institution's interpretation of such guidelines. Ultimately, however,
all animal procedures must be overseen by the local Animal Welfare and Ethical
Review Body and conducted under licences approved by a regulatory ethics
committee.
PMID- 25852853
TI - Pollen Allergies in Humans and their Dogs, Cats and Horses: Differences and
Similarities.
AB - Both humans and their most important domestic animals harbor IgE and a similar
IgE receptor repertoire and expression pattern. The same cell types are also
involved in the triggering or regulation of allergies, such as mast cells,
eosinophils or T-regulatory cells. Translational clinical studies in domestic
animals could therefore help cure animal allergies and at the same time gather
knowledge relevant to human patients. Dogs, cats and horses may spontaneously and
to different extents develop immediate type symptoms to pollen allergens. The
skin, nasal and bronchial reactions, as well as chronic skin lesions due to
pollen are in principle comparable to human patients. Pollen of various species
most often causes allergic rhinitis in human patients, whereas in dogs it elicits
predominantly eczematous lesions (canine atopic dermatitis), in horses recurrent
airway obstruction or hives as well as pruritic dermatitis, and in cats bronchial
asthma and so-called cutaneous reactive patterns (eosinophilic granuloma complex,
head and neck pruritus, symmetric self-induced alopecia). In human allergy
specific IgE detection, skin tests or other allergen provocation tests should be
completed. In contrast, in animals IgE and dermal tests are regarded as equally
important and may even replace each other. However, for practical and economic
reasons intradermal tests are most commonly performed in a specialized practice.
As in humans, in dogs, cats and horses allergen immunotherapy leads to
significant improvement of the clinical symptoms. The collected evidence suggests
that canines, felines and equines, with their spontaneous allergies, are
attractive model patients for translational studies.
PMID- 25852855
TI - Magnesium: a renewed player of vascular ageing in diabetic CKD patients?
PMID- 25852856
TI - Amyloid nephropathy.
AB - Amyloidosis is an uncommon disease that is characterized by abnormal
extracellular deposition of misfolded protein fibrils leading to organ
dysfunction. The deposited proteins display common chemical and histologic
properties but can vary dramatically in their origin. Kidney disease is a common
manifestation in patients with systemic amyloidosis with a number of
amyloidogenic proteins discovered in kidney biopsy specimens. The emergence of
mass spectrometry-based proteomics has added to the diagnostic accuracy and
overall understanding of amyloidosis. This in-depth review discusses the general
histopathologic features of renal amyloidosis and includes an in-depth discussion
of specific forms of amyloid affecting the kidney.
PMID- 25852857
TI - Clinicopathological assessment of the nephron number.
AB - Recent studies have demonstrated much larger variability in the total number of
nephrons in normal populations than previously suspected. In addition, it has
been suggested that individuals with a low nephron number may have an increased
lifetime risk of hypertension or renal insufficiency, emphasizing the importance
of evaluating the nephron number in each individual. In view of the fact that all
previous reports of the nephron number were based on analyses of autopsy kidneys,
the identification of surrogate markers detectable in living subjects is needed
in order to enhance understanding of the clinical significance of this parameter.
In this review, we summarize the clinicopathological factors and findings
indicating a reduction in the nephron number, focusing particularly on those
found at the time of a preserved renal function.
PMID- 25852858
TI - Oedema, solid organ transplantation and mammalian target of rapamycin
inhibitor/proliferation signal inhibitors (mTOR-I/PSIs).
AB - Mammalian target of rapamycin inhibitor (mTOR-I)/proliferation signal inhibitors
(PSI) including sirolimus and everolimus represent a new class of drugs
increasingly used in solid-organ transplantation as alternatives to calcineurin
inhibitors for patients with renal dysfunction, transplant coronary arterial
vasculopathy or malignancy. The most frequently occurring mTOR-I/PSI-related
adverse events are similar to those associated with other immunosuppressive
therapies, but some side effects are more characteristic of proliferation signal
inhibitors (e.g. lymphocele, arthralgia, oedema and hyperlipidaemia). The present
paper review incidence, clinical presentation and mechanism of oedema within the
clinical experience of mTOR-I/PSI in solid organ transplantation.
PMID- 25852859
TI - HIV medication-based urolithiasis.
AB - Drug-induced renal calculi represent 1-2% of all renal calculi. In the last
decade, drugs used for the treatment of HIV-infected patients have become the
most frequent cause of drug-containing urinary calculi. Among these agents,
protease inhibitors (PIs) are well known to induce kidney stones, especially
indinavir and atazanavir, and more recently darunavir. Urolithiasis attributable
to other PIs has also been reported in clinical cases such as those during non-PI
use. Antiretroviral drug-induced calculi deserve consideration because most of
them are potentially preventable. This article summarizes the diagnosis,
epidemiology, prevention and management of antiretroviral drug-induced
urolithiasis.
PMID- 25852860
TI - Severe hyperkalaemia: demographics and outcome.
AB - BACKGROUND: Few studies have evaluated the prevalence of severe hyperkalaemia in
unselected patient populations. We identified all episodes of severe
hyperkalaemia occurring in 1 year, and described patient demographics, clinical
response and outcome. We also assessed junior doctor knowledge of its causes and
significance. MATERIALS AND METHODS: A retrospective interrogation of the
database of the regional biochemical laboratory identified all episodes of severe
hyperkalaemia (K>= 6.5 mmol/L) occurring in 2011. The understanding of trainee
doctors of the importance, causes and treatment of severe hyperkalaemia was
assessed by structured questionnaire. RESULTS: Severe hyperkalaemia was recorded
in 433 samples (365 patients) giving a prevalence of 0.11%. Thirty-six per cent
of episodes occurred in patients under the care of a nephrologist, who were
significantly younger than those not under the care of a nephrologist. In the
nephrology cohort, 86% occurred in patients with chronic kidney disease (CKD),
the majority of which had CKD Stage 5. In the non-nephrology cohort, only 65%
occurred in the context of CKD, which was equally distributed between Stages 3
and 5 CKD. In both patient groups, roughly 50% of episodes occurred in
association with acute kidney injury (AKI). Acute mortality (death within 48 h of
documented severe hyperkalaemia) was higher in the non-nephrology compared with
the nephrology cohort. Time to repeat serum potassium was influenced by the
clinical setting with shorter time to repeat for acute care compared with ward
settings. Assessment of trainee doctor's knowledge suggested significant
deficiencies in relation to severe hyperkalaemia. CONCLUSIONS: The prevalence of
severe hyperkalaemia was low and occurred predominantly in the context of CKD
and/or AKI. The majority of episodes occurred in patients not under the care of a
nephrologist. Variability in time to repeat serum potassium levels suggested
deficiencies in care, and assessment of trainee doctor's knowledge suggests the
need for further educational initiatives to highlight its importance.
PMID- 25852861
TI - Renal manifestations of tuberous sclerosis among children: an Indian experience
and review of the literature.
AB - OBJECTIVE: The objective of this study was to describe the renal manifestations
in children 0-18 years of age diagnosed with tuberous sclerosis complex (TSC) at
a tertiary hospital in South India. METHODS: Data of children with TSC, who
presented to Christian Medical College Vellore Hospital from January 2008 to
January 2013, were analysed by a retrospective chart review. The cases were
identified from outpatient records and underwent ultrasonography, urine analysis
and examination of serum creatinine to recognize renal involvement. RESULTS:
Twenty-five children with TSC were identified. Two children did not have imaging
studies available and were excluded from the analysis. The age of the included
children ranged from 5 days to 15 years with a median age of 8 years. Seventy
four per cent (17/23) were males. Ten of the 23 children had evidence of renal
involvement (43.5%). Of the 10 children with renal involvement, 6 had
angiomyolipoma (60%), 5 had renal cysts (50%) and 1 had suspected renal cell
carcinoma. In two children both angiomyolipoma (AML) and cysts were noted. One
child was found to have proteinuria. The rest of the children had no evidence of
proteinuria and had normal creatinine clearance. CONCLUSION: We conclude that all
children with TSC should be screened for renal involvement and regular follow-up
should be arranged.
PMID- 25852862
TI - Polycystic kidney size and outcomes on peritoneal dialysis: comparison with
haemodialysis.
AB - BACKGROUND: For many nephrologists, patients with polycystic kidney disease (PKD)
have an increased risk of complications and technique failure on peritoneal
dialysis (PD) due to enlarged kidneys. The literature showed that PD can be as
good a therapeutic option as haemodialysis (HD) for patients with PKD. However,
no study has focused on the impact of polycystic kidney size on outcomes for
patients on PD. METHODS: This is a retrospective monocentric study. Fifty-eight
patients with PKD started dialysis between January 2000 and December 2010: 24 on
PD and 34 on HD. Kidney size assessed by abdominal computed tomography scans was
available for 45 patients (19 on PD and 26 on HD). PD technique survival,
specific PKD complications and mechanical and infectious PD complications, as
need for pre-transplant nephrectomy and kidney transplantation, were considered.
RESULTS: The two cohorts were similar in terms of age and body surface area. The
median kidney size was not significantly different between PD and HD patients
[19.1 cm (12.5-32.5) versus 16.5 cm (11.8-33.8), respectively, P = 0.13].
However, we identified an increased number of PD patients with larger kidneys
[(>25 cm) (27.8% on PD versus 7.7% on HD (P = 0.07)]. Neither cystic (infection
or haemorrhage) nor mechanical complications (hernias and leaks) were different
in PD or HD. Ten patients experienced PD-related peritonitis, mainly due to non
enteric bacterial pathogens. The main reason for stopping PD and HD was
transplantation. Six PD patients underwent nephrectomy in order to access the
transplant programme. Among them, five were maintained on PD after surgical
procedure with good adequacy dialysis criteria. CONCLUSIONS: We observed no
deleterious impact of kidney size on outcomes on PD when compared with HD. A
large kidney size in patients with PKD is not a contraindication to PD. Patients
for whom a pre-transplant nephrectomy is mandatory can also safely opt for PD as
a dialysis method.
PMID- 25852863
TI - How good are we at managing acute kidney injury in hospital?
AB - INTRODUCTION: Acute kidney injury (AKI) is a common clinical problem associated
with adverse outcomes. This study identifies the incidence of AKI in two UK
district general hospitals' without on-site renal services and assesses AKI
management and level of nephrologist input. METHODS: The AKIN classification was
used to identify 1020 AKI patients over 6 months. Data were collated on patient
demographics, AKI management and referral to nephrology and intensive care
services. Short/long-term renal outcomes were investigated. Patients were
followed up for 14 months post-discharge. RESULTS: Incidence of hospital-based
AKI was 6.4%. Mean patient age was 73 years. There was 28.1% acute in-hospital
mortality with a further 21.6% 14-month mortality. Only 8.3% of patients were
referred to nephrology services for in-hospital review, and only 8.1% had
outpatient nephrology follow-up. Compliance with the AKI National Confidential
Enquiry into Patient Outcomes and Deaths (NCEPOD) recommendations was poor with
32.8% of patients having renal imaging and 15% of patients having acid-base
status assessed. NCEPOD compliance improved with nephrology input. Patients
referred to nephrology were likely to be younger with pre-existing CKD and severe
AKI. 10.5% of AKI episodes were unrecognized. Forty percent of those with
unrecognized AKI, (compared with 15% of recognized AKI) developed de novo or
progression of pre-existing CKD. CONCLUSION: AKI in DGHs is mostly managed
without nephrology input. There are significant shortcomings in AKI recognition
and management in this setting. This is associated with poor mortality and long
term CKD. This study supports a need to improve the teaching and training of
front-line medical staff in identifying AKI. Additionally, implementation of AKI
e-alert systems may encourage early recognition and provide a prompt for renal
referral.
PMID- 25852864
TI - Low serum sodium is associated with protein energy wasting and increased
interdialytic weight gain in haemodialysis patients.
AB - BACKGROUND: Low serum sodium (Na) has been associated with decreased body mass
index and increased cardiovascular mortality in haemodialysis (HD) patients. We
examined the relationship between serum Na and selected nutritional parameters of
protein energy wasting that are not affected from the hydration status in a
cohort of HD patients. METHODS: Triceps skinfold thickness (TSF), mid-arm
circumference (MAC), mid-arm muscle circumference (MAMC), handgrip strength (HGS)
and subjective global assessment (SGA) were assessed in maintenance HD patients
using standard techniques. MAMC was calculated with the formula MAMC (cm) = MAC
(cm) -3.142 * TSF cm. Pre-dialysis serum Na values from routine monthly
laboratory measurements were averaged for the last 6 months prior to the
nutritional assessment. RESULTS: Altogether 172 patients with anthropometric data
were included in the final analysis. Mean age was 66 +/- 14, females 62 (36%) and
diabetics 48 (28.9%). Patients with pre-dialysis serum Na below the mean value
(136.2 mEq/L) had lower MAMC, HGS, SGA scores and albumin levels (23.50 +/- 3.16
cm versus 24.58 +/- 3.71 cm, P = 0.048; 21.7 +/- 13.6 kg versus 28.0 +/- 12.4 kg,
P = 0.030; 5.1 +/- 1.2 versus 5.7 +/- 1.0, P = 0.012 and 31.65 +/- 4.73 mg/L
versus 32.25 +/- 3.91 mg/L, P = 0.022, respectively) and higher interdialytic
weight gains. Pre-dialysis serum Na correlated positively with MAMC, handgrip and
SGA (Pearson's correlation r = 0.165, P = 0.031, r = 0.237, P = 0.022 and r =
0.195, P = 0.011, respectively). CONCLUSION: This study demonstrates that low
serum sodium is associated with protein energy wasting and increased
interdialytic weight gain in HD patients.
PMID- 25852866
TI - The significance of tubuloreticular inclusions as a marker of systemic
stimulation by interferons in a case of focal and segmental glomerulosclerosis
associated with cytomegalovirus (CMV) infection.
AB - The identification of large numbers of tubuloreticular inclusions (TRIs) in renal
biopsies may be useful to raise diagnostic suspicion for certain clinical
entities, particularly autoimmune diseases and viral infections. We report a case
of a 65-year-old female with a 2-week history of malaise, massive proteinuria and
lower extremity edema of acute onset. A renal biopsy was performed and the
diagnosis of non-human immunodeficiency virus (HIV) tip-located, early focal
segmental glomerulosclerosis (FSGS) was established. The electron microscopy
examination was remarkable for the presence of diffuse foot process effacement
and frequent TRIs in the endothelial cells of the glomerular capillary loops,
endothelium of arterioles and cytoplasm of fibroblasts in the interstitium,
highly suggestive of an underlying etiology. Patient clinical and laboratory
workup revealed the absence of an autoimmune disease but the presence of a
subclinical cytomegalovirus (CMV) infection. Therefore, we highlight that the
identification of TRIs is a useful indicator of systemic interferon activity. In
the present case, the unusual location of numerous TRIs was associated with a
subclinical CMV infection in an immunocompetent patient.
PMID- 25852865
TI - Magnesium and FGF-23 are independent predictors of pulse pressure in pre-dialysis
diabetic chronic kidney disease patients.
AB - BACKGROUND: The aim of our study was to evaluate the relevance of magnesium and
FGF-23 in terms of cardiovascular disease in a population of type 2 diabetic
patients with nephropathy. METHODS: In a cross-sectional study, we included 80
type 2 diabetic patients with chronic kidney disease (CKD) stages 2, 3 and 4. We
analysed mineral metabolism, inflammation, oxidative stress and insulin
resistance. Our population was divided into two groups according to their pulse
pressure (PP) as follows: G-1 with PP < 50 mmHg (n = 34) and G-2 with PP >= 50
mmHg (n = 46). RESULTS: We found that G-2 patients showed lower calcium (P =
0.004), eGFR (P = 0.001), magnesium (P = 0.0001), osteocalcin (P = 0.0001) and
25(OH)D3 (P = 0.001), and higher iPTH (P = 0.001), FGF-23 (P = 0.0001),
malonaldehyde (P = 0.0001), interleukin 6 (P = 0.001) and HOMA-IR (P = 0.033). No
differences were found between the two groups regarding age, duration of disease,
haemoglobin, HgA1c and phosphorus. In a multivariate analysis, we found that FGF
23 and magnesium independently influenced the PP [OR = 1.239 (1.001-2.082), P =
0.039 and OR = 0.550 (0.305-0.727), P = 0.016, respectively]. CONCLUSIONS: In our
diabetic population with early stages of CKD, FGF-23 as well as lower magnesium
levels were significantly and independently associated with higher PP levels, an
established marker of cardiovascular morbidity and mortality.
PMID- 25852867
TI - Touch not the cat bot a glove*: ANCA-positive pauci-immune necrotizing
glomerulonephritis secondary to Bartonella henselae.
AB - A 36-year-old male presented with a secondary, but anti-neutrophil cytoplasmic
antibody (ANCA) (proteinase-3) positive, vasculitis with renal insufficiency due
to a pauci-immune necrotizing glomerulonephritis. An infective process was
initially excluded by blood cultures and an echocardiogram prior to
immunosuppression. The patient's condition failed to improve and re-evaluation
confirmed infective endocarditis requiring valve replacement. Subsequent tissue
cultures identified Bartonella henselae. Antibiotic treatment led to full
resolution of physical, biochemical and immunological markers. This is the first
case of B. henselae endocarditis-associated ANCA positivity with a pauci-immune
glomerulonephritis. It demonstrates the importance of revisiting standard
investigations in patients not improving expectantly on conventional therapy.
PMID- 25852868
TI - Sarcoid-like lung granulomas in a hemodialysis patient treated with a dipeptidyl
peptidase-4 inhibitor.
AB - It has been reported that the inhibition of dipeptidyl peptidase-4 (DPP-4)/CD26
on T-cells by DPP-4 enzymatic inhibitors suppresses lymphocyte proliferation and
reduces the production of various cytokines, including tumor necrosis factor
(TNF)-alpha. A 72-year-old female with diabetic nephropathy on hemodialysis
developed multiple lung nodules following the administration of vildagliptin. A
biopsy demonstrated the histology of granulomas without caseous necrosis. The
discontinuation of vildagliptin resulted in the disappearance of the granulomas
within 4 months. As granulomatosis often develops in patients under anti-TNF
alpha therapy, the accumulation of DPP-4 inhibitors or its metabolites is
possibly linked to unrecognized complications, such as sarcoid-like lung
granulomas.
PMID- 25852869
TI - Tumor-induced osteomalacia with normal systemic fibroblast growth factor-23
level.
AB - A 38-year-old man presenting with long bone/rib fractures was diagnosed with
tumor-induced osteomalacia (TIO) caused by a giant cell tumor in the right foot
with normal systemic fibroblast growth factor-23 (FGF23) levels. Multiple imaging
modalities done initially and one year later were unable to localize the tumor.
New-onset foot pain discovered a right foot mass with resolution of metabolic
abnormalities post-surgery. Sampling from both femoral veins showed an elevated
FGF23 value on the right side. This case is unique in that the patient had a
normal systemic FGF23 level even with severe clinical manifestations of TIO.
PMID- 25852870
TI - Nephrotic-range proteinuria on interferon-beta treatment: immune-induced
glomerulonephritis or other pathway?
AB - We present a case report of a 37-year-old woman with multiple sclerosis (MS) who
developed nephrotic-range proteinuria secondary to membrano proliferative
glomerulonephritis (MPGN)-like disease with mesangial C3 deposition without
evidence of immune-complex deposition in the context of long-term interferon-beta
(IFN-beta) therapy. The complete remission of proteinuria following cessation of
IFN-beta, strongly suggests causality. To our knowledge, this is the second case
report of MPGN associated with IFN-beta use. This being the case, the negative
immune screen, normal inflammatory markers and the absence of immune complex
deposits would imply a different pathway to that previously suggested.
PMID- 25852871
TI - Rare complication of a dialysis catheter insertion.
AB - Insertion of a dialysis catheter is a very common procedure in renal medicine,
which is associated with one or more complications in ~15% of patients. Central
venous catheter vascular erosion is a rare but serious complication, the
incidence appears to be between 0.4 and 1% which can be difficult to diagnose,
leading to increased morbidity and mortality. We report a case of a persistent
left-sided superior vena cava (PLSVC) and a possible central venous catheter
vascular erosion following insertion of a left-sided internal jugular dialysis
catheter. We discuss the mechanisms, diagnosis and measures to limit vascular
erosion and also briefly discuss PLSVC.
PMID- 25852872
TI - Membrane and centrifugal therapeutic plasma exchange: practical difficulties in
anticoagulating the extracorporeal circuit.
AB - Therapeutic plasma exchange (TPE) is a well-established treatment modality for
nephrology patients, using two conventional methods: membrane (mTPE) or
centrifugal TPE (cTPE). Although the efficacy of both treatments has been
described, there are few reports that compare these methodologies. Here we
describe three nephrology patients who were treated with both mTPE and cTPE. The
mTPE method, but not the cTPE method, was associated with persistent difficulty
anticoagulating the extracorporeal circuit in all three patients. In mTPE
procedures, the doses of heparin bolus and infusion rate were important
determinants of whether the circuit clotted. With a heparin bolus at or below
2000 IU, clotting occurred in 67% of treatments, dropping to 25% with a bolus of
>2000 IU. Likewise, a heparin infusion rate during the procedure was indicative
of clotting. With a maintenance infusion of <2000 IU/h, most circuits clotted. No
clotting was observed during cTPE procedures using acid citrate dextrose formula
A solution as an anticoagulant of the extracorporeal circuit. Overall,
difficulties maintaining the extracorporeal circuit in mTPE required the use of
additional disposable sets, high doses of heparin and nursing time. In addition,
mTPE procedures took longer to perform than cTPE.
PMID- 25852873
TI - Hemodialysis-associated endovascular device infection.
PMID- 25852874
TI - Ganciclovir-resistant cytomegalovirus infection in renal transplantation.
PMID- 25852875
TI - Hypomagnesemia and hypokalemia: a successful oral therapeutic approach after 16
years of potassium and magnesium intravenous replacement therapy.
PMID- 25852876
TI - Nephrocalcinosis in primary Sjogren's syndrome.
PMID- 25852877
TI - Colchicine-resistant familial Mediterranean fever in a renal transplantation
patient: successful treatment with anakinra.
PMID- 25852878
TI - Acute interstitial nephritis following viper bite: a rare association.
PMID- 25852879
TI - Influenza and pneumococcal vaccinations in dialysis patients.
PMID- 25852880
TI - The 20th anniversary of BANTAO (Balkan Cities Association of Nephrology,
Dialysis, Transplantation and Artificial Organs).
PMID- 25852882
TI - Insulin for the treatment of hyperkalemia: a double-edged sword?
PMID- 25852881
TI - Renal replacement therapy in Europe: a summary of the 2011 ERA-EDTA Registry
Annual Report.
AB - BACKGROUND: This article provides a summary of the 2011 ERA-EDTA Registry Annual
Report (available at www.era-edta-reg.org). METHODS: Data on renal replacement
therapy (RRT) for end-stage renal disease (ESRD) from national and regional renal
registries in 30 countries in Europe and bordering the Mediterranean Sea were
used. From 27 registries, individual patient data were received, whereas 17
registries contributed data in aggregated form. We present the incidence and
prevalence of RRT, and renal transplant rates in 2011. In addition, survival
probabilities and expected remaining lifetimes were calculated for those
registries providing individual patient data. RESULTS: The overall unadjusted
incidence rate of RRT in 2011 among all registries reporting to the ERA-EDTA
Registry was 117 per million population (pmp) (n = 71.631). Incidence rates
varied from 24 pmp in Ukraine to 238 pmp in Turkey. The overall unadjusted
prevalence of RRT for ESRD on 31 December 2011 was 692 pmp (n = 425 824). The
highest prevalence was reported by Portugal (1662 pmp) and the lowest by Ukraine
(131 pmp). Among all registries, a total of 22 814 renal transplantations were
performed (37 pmp). The highest overall transplant rate was reported from Spain,
Cantabria (81 pmp), whereas the highest rate of living donor transplants was
reported from Turkey (39 pmp). For patients who started RRT between 2002 and
2006, the unadjusted 5-year patient survival on RRT was 46.8% [95% confidence
interval (CI) 46.6-47.0], and on dialysis 39.3% (95% CI 39.2-39.4). The
unadjusted 5-year patient survival after the first renal transplantation
performed between 2002 and 2006 was 86.7% (95% CI 86.2-87.2) for kidneys from
deceased donors and 94.3% (95% CI 93.6-95.0) for kidneys from living donors.
PMID- 25852883
TI - Central vasopressin: dendritic and axonal secretion and renal actions.
PMID- 25852884
TI - Hypoglycemia in the treatment of hyperkalemia with insulin in patients with end
stage renal disease.
AB - BACKGROUND: Hypoglycemia is common in patients with end-stage renal disease
(ESRD). We identified the incidence and timing of hypoglycemia and its risk
factors in hospitalized patients with ESRD after the treatment of hyperkalemia
with insulin. METHODS: We conducted a retrospective study of all hospitalized
adult patients treated with hemodialysis who received intravenous insulin to
treat hyperkalemia between 1 January 2011 and 31 December 2011. We identified
patients who became hypoglycemic [blood glucose <3.3 mmol/L (60 mg/dL)] after
insulin administration. RESULTS: Two hundred and twenty-one episodes of
hyperkalemia were treated with insulin, resulting in 29 episodes of hypoglycemia
(13%). Factors associated with a higher risk of hypoglycemia included no prior
diagnosis of diabetes [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.0-5.1,
P = 0.05], no use of diabetes medication prior to admission [OR 3.6, 95% CI 1.2
10.7, P = 0.02] and a lower pretreatment glucose level [mean 5.8 +/- 0.7 mmol/L
(104 +/- 12 mg/dL) versus 9.0 +/- 0.6 mmol/L (162 +/- 11 mg/dL), P = 0.04].
Hypoglycemia occurred at a median of 2 h after insulin administration and
persisted for a median of 2 h. CONCLUSIONS: The treatment of hyperkalemia with
insulin in hospitalized patients with ESRD may be complicated by hypoglycemia.
Patients with a history of diabetes are less susceptible to this complication.
Our study supports the use of a protocol to provide dextrose support and blood
glucose monitoring for at least 3 h after insulin treatment of hyperkalemia.
PMID- 25852885
TI - Multiple kidney cysts in thin basement membrane disease with proteinuria and
kidney function impairment.
AB - BACKGROUND: Some patients with thin basement membrane disease (TBMD) develop
proteinuria, hypertension and different degrees of CKD, besides the persistent
microhaematuria characteristic of the disease. Little is known about factors
associated with this unfavourable outcome. METHODS: We reviewed clinical,
pathological and radiological features of 32 patients with biopsy-proven TBMD.
Patients were divided in two groups: those with persistent normal kidney function
and negative or minimal proteinuria (n = 16) and those with persistent
proteinuria >0.5 g/day (n = 16). RESULTS: Patients with proteinuria had a worse
kidney function at baseline than those with negative proteinuria. Global or
segmental glomerulosclerosis, together with interstitial fibrosis, was found in
37% of patients with proteinuria. All proteinuric patients were treated with
renin-angiotensin system blockers. At the end of follow-up (198 months in
proteinuric patients and 210 months in patients with negative proteinuria) the
prevalence of hypertension was 68% in proteinuric patients (12% at baseline),
compared with 12 and 6%, respectively, in non-proteinuric patients. A slow
decline of renal function was observed in proteinuric patients, although no
patient developed end-stage kidney disease. Ultrasound studies showed bilateral
kidney cysts in nine patients (56%) with proteinuria. Cysts were bilateral and
countless in six patients, and bilateral but with a limited number of cysts in
the three remaining patients. No cysts were found in patients with negative
proteinuria. CONCLUSIONS: Some patients with TBMD develop hypertension,
proteinuria and CKD. Multiple bilateral kidney cysts were found in a majority
(56%) of these patients. Further studies are needed to investigate the
pathogenesis and the influence on long-term outcome of this TBMD-associated
multiple kidney cysts.
PMID- 25852887
TI - Minimally invasive fluoroscopic percutaneous peritoneal dialysis catheter
salvage.
AB - BACKGROUND: Peritoneal dialysis catheter (PDC) dysfunction can often be treated
fluoroscopically by manipulation with wire, balloon or stiff stylet, saving
surgical intervention for refractory cases. We describe an enhanced percutaneous
approach to PDC salvage that can lead to a more definitive intervention and
salvage for cases refractory to fluoroscopic manipulation. METHODS: In five cases
of PD catheter malfunction, the deep cuff was dissected free after a 0.035
hydrophilic wire was passed into the peritoneum through the PDC. Only the
intraperitoneal portion of the PDC was explanted. The PDC was cleared of
obstruction and omentum. The intraperitoneal portion of the PDC was reimplanted
over wire via a peel-away sheath and the deep cuff sutured. RESULTS: Omental
entrapment was present in three of five patients and fibrin occlusion in four of
the five cases. All catheters were repaired successfully by the described
technique. Post procedure, 3-5 days of lower volume, recumbent PD exchanges were
performed prior to full-dose PD. No perioperative complications or leaks were
noted. All PDCs were patent at 6 months. One patient required laparoscopy for
recurrent omental wrapping 3 months post intervention. CONCLUSIONS: PDC salvage
in this manner is a cost-effective alternative to laparoscopic repair of PDCs
failing catheter manipulation. The infection barrier afforded by the original
superficial cuff and subcutaneous tunnel is maintained. PD can be resumed
immediately. Only refractory cases need laparoscopy. This procedure allows for a
more definitive correction of catheter migration and obstruction, avoids
placement of a new PDC or temporary hemodialysis, is cost-effective and expands
percutaneous options for dysfunctional PD catheters.
PMID- 25852886
TI - Falls among hemodialysis patients: potential opportunities for prevention?
AB - BACKGROUND: Falls among patients undergoing maintenance hemodialysis (HD) have
significant consequences for quality of life and functional independence,
morbidity, healthcare utilization and even mortality, but studies on the etiology
of falls within large HD cohorts are limited. METHODS: Falls during the past 12
months were ascertained for a prevalent multi-center HD cohort (n = 762) aged 20
92 years, and associations with demographic and treatment characteristics,
comorbidities, cognitive function, prescribed medications, balance tests, frailty
and depressive symptoms were assessed. RESULTS: Falls were sustained by 28.4% of
participants. In multivariable-adjusted analyses, participants classified as
frail were over two times more likely to report falls [odds ratio (OR): 2.39, 95%
confidence interval (CI): 1.22-4.71, P = 0.01], and participants with a CES-D
score 18+ and/or prescribed antidepressants were over 80% more likely to be
fallers (OR: 1.83, 95% CI: 1.23-2.74, P = 0.003) than were participants with a
CES-D score <18 and no prescribed antidepressants. CONCLUSIONS: Frailty and
depressed mood, factors that are potentially modifiable, are prominently
associated with falls.
PMID- 25852888
TI - Distinct cytokine mRNA expression pattern in immunoglobulin G4-related kidney
disease associated with renal cell carcinoma.
AB - We treated a 61-year-old man with immunoglobulin (Ig)G4-related kidney disease
(IgG4-RKD). He had a history of allergic diseases and an allergic reaction and
had received a diagnosis of autoimmune pancreatitis (AIP). He had also received a
diagnosis of renal cell carcinoma (RCC) and had undergone segmental resection of
the left kidney at 59 years of age. His serum amylase level and number of
peripheral eosinophils increased after RCC development. We hypothesized that the
RCC may have induced AIP and IgG4-RKD and we therefore examined the excised RCC
tissue; typical findings of IgG4-RKD associated with RCC were recognized. We next
evaluated the mRNA expression of cytokines in the excised tissues of this case
and ten other ordinary RCC cases. In all cases, notable levels of IL-10 mRNA and
high levels of TGF-beta mRNA were seen. Although prominent differences were not
observed in the mRNA expression of Th1, Th17 and Treg cytokines in all cases, the
present case alone showed increased production of the Th2 cytokines IL-4 and IL
5, which were not detected in ordinary RCC cases. Although the mechanism
underlying IgG4-RKD development has not yet been determined, Th2 and Treg cells
are thought to play a prominent role in the pathogenesis. It is therefore likely
that in this case, the association of these two diseases was not coincidental,
and a distinct immune response against RCC may trigger IgG4-RKD development.
PMID- 25852889
TI - Delta-He: a novel marker of inflammation predicting mortality and ESA response in
peritoneal dialysis patients.
AB - BACKGROUND: Inflammation impairs erythropoiesis, iron availability and is
associated with a higher mortality risk in patients with end-stage renal disease.
We studied the associations between Delta-He [the difference between the
reticulocyte haemoglobin content (Ret-He) and erythrocyte haemoglobin content], a
suggested marker of iron availability, and markers of inflammation, iron status,
response to erythropoiesis-stimulating agents (ESAs) and mortality in prevalent
peritoneal dialysis (PD) patients. METHODS: Eighty-two PD patients were followed
weekly for 12 weeks with an additional follow-up of 36 months. Delta-He, Ret-He
and high-sensitivity C-reactive protein (hs-CRP) were measured weekly and
interleukin-6 (IL-6) and iron markers every fourth week. Mortality risk was
assessed by Cox proportional hazards model adjusting for potential confounding
factors. The relationships between ESA response, inflammatory markers, iron
markers and Delta-He were evaluated in the PD patients. The relationship between
Delta-He and iron markers was analysed in 87 healthy subjects. RESULTS: Delta-He
correlated with IL-6 (rho = 0.48, P < 0.001), hs-CRP (rho = 0.36, P < 0.001) and
ESA hyporesponsivess index (EHRI; rho = -0.44, P < 0.001) in the PD patients.
Delta-He did not correlate with iron markers in PD patients nor in healthy
subjects. The mean Delta-He levels were significantly different between the
tertiles of EHRI (P < 0.01). Delta-He was associated with all-cause mortality
risk in PD patients after adjusting for age, gender, hs-CRP, comorbidity and
nutritional status [OR 0.70 (0.51-0.96), P < 0.05]. CONCLUSIONS: Delta-He
independently predicts all-cause mortality in PD patients after adjusting for
potential confounders and is a predictor of ESA response in PD patients.
PMID- 25852890
TI - Two novel mutations of the CLDN16 gene cause familial hypomagnesaemia with
hypercalciuria and nephrocalcinosis.
AB - Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal
recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode
tight junction-associated proteins, claudin-16 and -19. The resultant tubulopathy
leads to urinary loss of Mg(2+) and Ca(2+), with subsequent nephrocalcinosis and
end-stage renal disease (ESRD). An 18-year-old boy presented with chronic kidney
disease and proteinuria, as well as hypomagnesaemia, hypercalciuria and
nephrocalcinosis. A kidney biopsy revealed tubular atrophy, interstitial fibrosis
and segmental sclerosis of some glomeruli. Two novel mutations in the CLDN16 gene
were identified: c.340C>T (nonsense) and c.427+5G>A (splice site). The patient
reached ESRD at 23 and benefited from kidney transplantation.
PMID- 25852891
TI - Allograft adenovirus nephritis.
AB - We present an uncommon case of allograft adenovirus tubulointerstitial nephritis
in a 63-year-old male 6 weeks following cadaveric renal transplantation for end
stage renal failure secondary to hypertensive nephrosclerosis. The patient
presented with acute onset of fevers, dysuria, haematuria and diarrhoea with
acute graft dysfunction. A renal biopsy demonstrated necrotizing
tubulointerstitial nephritis with viral cytopathic changes and no evidence of
rejection. Adenovirus was identified as the pathogen. Treatment involved the
reduction in the patient's usual immunosuppression, intravenous immunoglobulin,
piperacillin-tazobactam and ganciclovir. We present the clinical and pathological
findings of necrotizing adenoviral nephropathy, highlighting the importance of
considering this diagnosis in renal transplant recipients presenting with
interstitial nephritis in the setting of a systemic illness.
PMID- 25852892
TI - Sustained complete remission of steroid- and cyclophosphamide-resistant minimal
change disease with a single course of rituximab therapy.
AB - We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome
secondary to minimal-change disease occurring in an otherwise healthy 19-year-old
female, responding rapidly to two doses of rituximab therapy. Complete disease
remission has been sustained up to last follow-up (32 months) despite CD19
recovery. Literature review suggests emerging evidence that rituximab may have a
role to play in recurrent and/or refractory minimal-change disease.
PMID- 25852893
TI - Crystalloid glomerulopathy in monoclonal gammopathy of renal significance (MGRS).
AB - We report a case of monoclonal gammopathy of renal significance in a 63-year-old
man who presented with nephrotic-range proteinuria and renal insufficiency. The
kidney biopsy showed a membranoproliferative glomerulonephritis pattern with
extensive crystalloid deposits in the glomerular capillary endothelial cells and
very few in the tubular epithelial cells. The immunoperoxidase staining showed
kappa light chain restriction. Subsequently, the bone marrow showed 6% plasma
cells which confirmed the diagnosis of monoclonal gammopathy of renal
significance. He responded well to bortezomib treatment with resolution of the
nephrotic syndrome and normalization of renal function after 7 months.
PMID- 25852894
TI - Metabolic acidosis-induced hypercalcemia in an azotemic patient with primary
hyperparathyroidism.
AB - A 58-year-old man with Stage 3b chronic kidney disease and primary
hyperparathyroidism treated with cinacalcet was admitted for acute cholecystitis.
A cholecystostomy tube was placed, estimated glomerular filtration rate
decreased, metabolic acidosis developed and ionized calcium increased from 1.33
to 1.76 mM despite cinacalcet administration. A sodium bicarbonate infusion
corrected the metabolic acidosis restoring ionized calcium to normal despite no
improvement in renal function. The correlation between the increase in serum
bicarbonate and decrease in ionized calcium was r = -0.93, P < 0.001. In summary,
severe hypercalcemia was attributable to metabolic acidosis increasing calcium
efflux from bone while renal failure decreased the capacity to excrete calcium.
PMID- 25852895
TI - Steroid-resistant nephrotic syndrome with mutations in NPHS2 (podocin): report
from a three-generation family.
AB - Genetic causes of steroid-resistant nephrotic syndrome are being increasingly
recognized. Mutations in NPHS2, which encodes the glomerular protein podocin,
account for up to 17% of sporadic and 40% of familial cases, where they display
an autosomal-recessive pattern of inheritance. This report describes a non
consanguineous family with three generations of individuals who are either
compound heterozygotes for mutations in NPHS2 or who have inherited a mutation
and a non-neutral polymorphism (R229Q). As well as providing an aetiological
explanation, identifying pathogenic mutations and considering genotype-phenotype
correlations can provide prognostic information and lead to changes in genetic
counselling and management.
PMID- 25852896
TI - A severe phenotype of Gitelman syndrome with increased prostaglandin excretion
and favorable response to indomethacin.
AB - Our understanding of Gitelman syndrome (GS) and Bartter syndrome has continued to
evolve with the use of genetic testing to more precisely define the tubular
defects responsible. GS is caused by mutations in the SLC12A3 gene encoding the
Na(+)-Cl(-) co-transporter of the distal convoluted tubule (NCCT) and tends to be
associated with a milder salt-losing phenotype. We describe two female siblings
presenting in infancy with a severe salt-losing tubulopathy and failure to thrive
due to compound heterozygous mutations in the SLC12A3 gene encoding the NCCT.
Both children were treated with indomethacin resulting in improved linear growth
and polyuria. Some atypical biochemical findings in our cases are discussed
including raised urinary prostaglandin (PGE2) excretion that normalized with
intravenous fluid repletion.
PMID- 25852897
TI - Renal-limited thrombotic microangiopathy and acute interstitial nephritis with a
single dose of quinine.
AB - Quinine has been reported to cause acute kidney injury by various mechanisms. The
response to quinine can result in a spectrum of problems ranging from isolated
thrombocytopenia to thrombotic microangiopathy (TMA) to disseminated
intravascular coagulation. Quinine has also been reported to cause acute
interstitial nephritis (AIN). We report an unusual presentation where both of
these entities of renal-limited TMA and AIN were precipitated by a single dose of
quinine.
PMID- 25852898
TI - Fever of unknown origin in a haemodialysis patient: a late diagnosis requiring a
novel treatment.
PMID- 25852899
TI - A day in the zoo.
PMID- 25852900
TI - High anion gap metabolic acidosis: use the proper acronym, discard the red
herrings and thou shall find the culprit.
PMID- 25852901
TI - Cyclophosphamide-induced toxic epidermal necrolysis: vigilance needed.
PMID- 25852902
TI - Nutcracker phenomenon in IgA nephropathy.
PMID- 25852903
TI - Adult orthostatic proteinuria.
PMID- 25852904
TI - Trimethylamine generation in patients receiving hemodialysis treated with l
carnitine.
PMID- 25852905
TI - Renal replacement therapy in Ukraine: epidemiology and international comparisons.
AB - BACKGROUND: Little is known about the status of renal replacement therapy (RRT)
in the post-Soviet countries. We therefore investigated the epidemiology and
treatment outcomes of RRT in Ukrainian patients and put the results into an
international perspective. METHODS: Data from the Ukrainian National Renal
Registry for patients on RRT between 1 January 2010 and 31 December 2012 were
selected. We calculated the incidence and prevalence of RRT per million
population (pmp) and the 3-, 12- and 24-month patient survival using the Kaplan
Meier method and Cox regression. RESULTS: There were 5985 prevalent patients on
RRT on 31 December 2012 (131.2 pmp). Mean age was 46.5 +/- 13.8 years, 56% men
and 74% received haemodialysis (HD), while peritoneal dialysis and kidney
transplantation both represented 13%. The most common cause of end-stage renal
disease was glomerulonephritis (51%), while only 12% had diabetes. In 2012, 1129
patients started dialysis (incidence 24.8 pmp), with 80% on HD. Mean age was 48
+/- 14 years, 58% men and 20% had diabetes. Three, 12- and 24-month patient
survival on dialysis was 95.1%, 86.0% and 76.4%, respectively. The transplant
rate in 2012 was 2.1 pmp. CONCLUSIONS: The incidence and prevalence of RRT and
the transplantation rate in Ukraine are among the lowest in Europe, suggesting
that the need for RRT is not being met. Strategies to reduce the RRT deficit
include the development and improvement of transplantation and home-based
dialysis programmes. Further evaluation of the quality of Ukrainian RRT care is
needed.
PMID- 25852906
TI - The eye: a window on kidney diseases.
PMID- 25852907
TI - Erdheim-Chester disease: from palliative care to targeted treatment.
AB - Erdheim-Chester disease (ECD) is a life-threatening multi-systemic non-Langerhans
histiocytosis with cardiovascular complications as the leading cause of death.
ECD affects the kidneys in up to 30% of cases, with fibrotic tissue deposition in
the perirenal fat and renal hilum. Diagnosis is usually based on histological
analysis of the pathologic tissue, which typically shows xanthogranulomatous
infiltrates of foamy CD68+/CD1a- histiocytes surrounded by fibrosis. A consistent
percentage of patients affected by ECD develop renal failure and hypertension as
a consequence of renal artery stenosis and hydronephrosis. These conditions have
been generally treated with the placement of stents and nephrostomies that
frequently led to disappointing outcomes. Before the introduction of interferon
alpha (IFNalpha) treatment, the mortality rate was as high as 57% in the long
term. Recent studies have granted new insights into the pathogenesis of ECD,
which seems to bear a dual component of clonal and inflammatory disease. These
advances led to use specific therapies targeting either the oncogenes
(BRAF(V600E)) or the effectors of the immune response implicated in ECD (IL-1,
TNFalpha). Drugs such as anakinra (recombinant human IL-1 receptor antagonist),
infliximab (monoclonal antibody against TNFalpha) and vemurafenib (inhibitor of
mutant BRAF) showed promising results in small single-centre series. Although
larger trials will be needed to address the impact of these drugs on ECD
prognosis and to select the most effective treatment, targeted therapies hold the
premises to drastically change the outcome of this condition.
PMID- 25852908
TI - Dent-Wrong disease and other rare causes of the Fanconi syndrome.
AB - Dent-Wrong disease, an X-linked recessive disorder of the proximal tubules,
presents with hypercalciuria, nephrocalcinosis, nephrolithiasis, renal
insufficiency, low-molecular-weight proteinuria, rickets and/or osteomalacia.
Dent and Friedman initially characterized the disorder in 1964 following studies
of two patients with rickets who presented with hypercalciuria,
hyperphosphaturia, proteinuria and aminoaciduria. Since then, extensive
investigation identified two genetic mutations (CLCN5 and OCRL1) to be associated
with Dent-Wrong disease. Clinical features supported by laboratory findings
consistent with proximal tubule dysfunction help diagnose Dent-Wrong disease.
Genetic analysis supports the diagnosis; however, these two genes can be normal
in a small subset of patients. The differential diagnosis includes other forms of
the Fanconi syndrome, which can be hereditary or acquired (e.g. those related to
exposure to exogenous substances). Treatment is supportive with special attention
to the prevention of nephrolithiasis and treatment of hypercalciuria. We review
the rare forms of Fanconi syndrome with special attention to Dent-Wrong disease.
PMID- 25852909
TI - Urinary angiotensinogen as a potential biomarker of diabetic nephropathy.
AB - BACKGROUND: Activation of the renin-angiotensin-aldosterone system (RAAS) is an
important mediator of diabetic nephropathy. Urinary angiotensinogen, a novel
biomarker of the intrarenal RAAS, is associated with progressive kidney injury.
In this study, the authors investigated the determinants of urinary
angiotensinogen and its associations with staging of diabetic nephropathy.
METHODS: Random urine samples were collected from the patients with type 2
diabetes with normoalbuminuria (n = 52), microalbuminuria (n = 52) and
macroalbuminuria (n = 51) for the measurement of angiotensinogen by sensitive and
specific ELISAs. Control samples were collected from healthy volunteers (n = 20)
who had normal albuminuria and renal function. RESULTS: Urinary angiotensinogen
was higher in microalbuminuric and macroalbuminuric diabetes than in controls
[63.44 (interquartile range, IQR: 22.08, 174.8) versus 398.38 (IQR: 205.03,
673.68) versus 9.12 (IQR: 3.76, 23.82) ng/mg creatinine, respectively, P <
0.001]. In diabetes with normoalbuminuria, urinary angiotensinogen was also
higher than in controls [16.42 (IQR: 7.69, 34.71) versus 9.12 (IQR: 3.76, 23.82)
ng/mg creatinine, P = 0.047]. The performance of the biomarker in differentiating
each stage of type 2 diabetes from controls was illustrated by receiver-operating
characteristic curves. The areas under the curve for the diagnosis of established
normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes using
urine angiotensinogen (ng/mg creatinine) were 0.62 (95% CI: 0.48-0.77), 0.85 (95%
CI: 0.76-0.94) and 0.96 (95% CI: 0.92-1.00), respectively. In addition, the cut
off levels were 9.30 ng/mg (sensitivity 65.4%, specificity 55.0%), 12.32 ng/mg
(sensitivity 55.8%, specificity 65.0%) and 17.44 ng/mg (sensitivity 44.2%,
specificity 70.0%), respectively, for distinguishing normoalbuminuric type 2
diabetes from healthy controls. CONCLUSIONS: The authors propose that
angiotensinogen could be one of the potential urinary biomarkers for diagnosis in
established diabetic nephropathy. It appeared even before the significant
albuminuria in diabetic nephropathy. It might be useful as an early biomarker of
activation of the renin-angiotensin system in diabetic nephropathy.
PMID- 25852910
TI - Measuring pain in patients undergoing hemodialysis: a review of pain assessment
tools.
AB - BACKGROUND: Patients undergoing hemodialysis frequently report pain with
multifactorial causes, not limited to that experienced directly from hemodialysis
treatment. Their pain may be nociceptive, neuropathic, somatic or visceral in
nature. Despite this, pain in this population remains under-recognized and under
treated. Although several tools have been used to measure pain in patients
undergoing hemodialysis as reported in the literature, none of them have been
validated specifically in this population. The objective for this review was to
compare and contrast these pain assessment tools and discuss their clinical
utility in this patient population. METHODS: To identify pain assessment tools
studied in patients undergoing hemodialysis, a literature search was performed in
PubMed and Medline. An expert panel of dialysis and pain clinicians reviewed each
tool. Each pain assessment tool was assessed on how it is administered and
scored, its psychometric properties such as reliability, validity and
responsiveness to change, and its clinical utility in a hemodialysis population.
Brief Pain Inventory, McGill Pain Questionnaire, Pain Management Index, Edmonton
Symptom Assessment System, Visual Analogue Scale and Faces Pain Scale were
evaluated and compared. RESULTS: This assessment will help clinicians practicing
in nephrology to determine which of these pain assessment tools is best suited
for use in their individual clinical practice.
PMID- 25852911
TI - Three-month variation of plasma pentraxin 3 compared with C-reactive protein,
albumin and homocysteine levels in haemodialysis patients.
AB - BACKGROUND: Inflammatory markers vary considerably over time in haemodialysis
(HD) patients, yet the variability is poorly defined. The aim of the study was to
assess changes of plasma levels of pentraxin-3 (PTX-3), C-reactive protein (CRP),
albumin and homocysteine (Hcy) over 3 months and the association between the
changes in these biomarkers and mortality. METHODS: In 188 prevalent HD patients,
inflammatory markers were measured at inclusion and after 3 months. Mortality was
recorded during a median follow-up of 41 months. The changes of the biomarker
levels were categorized according to change in tertile for the specific
biomarker. The variation was calculated as the intra-class correlation (ICC).
Mortality was analysed by Kaplan-Meier and Cox proportional hazards model. The
predictive strength was calculated for single measurements and for the variation
of each inflammatory marker. RESULTS: The intra-individual variation (low ICC)
was largest for PTX-3 [ICC 0.44; 95% confidence interval (CI): 0.33-0.55],
albumin (ICC 0.58; 95% CI: 0.49-0.67) and CRP (ICC 0.59; 95% CI: 0.51-0.68) and
lowest for Hcy (ICC 0.81; 95% CI: 0.77-0.86). During follow-up, 88 patients died.
CONCLUSIONS: PTX-3 measurements are less stable and show higher variation within
patients than CRP, albumin and Hcy. Persistently elevated PTX-3 levels are
associated with high mortality. Moreover, in multivariate logistic regression we
found that stable high PTX-3 adds to the mortality risk, even after inclusion of
clinical factors and the three other biomarkers. The associations of decreasing
albumin levels as well as low Hcy levels with worse outcome reflect protein
energy wasting.
PMID- 25852912
TI - Acute kidney injury due to decompression illness.
AB - Decompression illness is a rare but serious complication of diving caused by
intravascular or extravascular gas bubble formation. We report the first case of
acute kidney injury in a 27-year-old diver following three rapid ascents. He
presented with transient neurological symptoms and abdominal pain followed by
rapidly progressive acute kidney injury (creatinine peak 1210 umol/L) due to
arterial air emboli. He received supportive care and 100% oxygen followed by
hyperbaric therapy and recovered fully. Arterial air emboli caused by rapid
decompression can affect multiple organs including the kidneys. Early transfer to
a hyperbaric unit is important as complications may present delayed.
PMID- 25852913
TI - Sarcoidosis presenting as severe renin-dependent hypertension due to kidney
vascular injury.
AB - Renal sarcoidosis embraces a wide variety of clinical patterns. Renal vascular
involvement has seldom been reported and usually in the setting of systemic
vasculitis. We report the case of a 22-year-old patient in whom inaugural
manifestation of renal sarcoidosis consisted of severe hypertension associated
with bilateral perfusion defects and tumour-like nodules. In the setting of renal
sarcoidosis, our case suggests that renin-dependant hypertension may arise from
renal ischaemia as a result of extrinsic compression of kidney blood vessels due
to severe granulomatous inflammation.
PMID- 25852914
TI - Hypotension-induced blindness in haemodialysis patients.
AB - Hypotension is a commonly encountered complication in haemodialysis patients and
is a significant cause of morbidity and mortality. Bilateral visual loss in
dialysis induced hypotension remains poorly recognized as a complication by both
renal physicians and ophthalmologists. We report 2 cases of patients on renal
dialysis who suffered severe longstanding hypotension with bilateral non
arteritic anterior ischaemic optic neuropathy. Both patients experienced
bilateral loss of vision over a short time period. We feel that physicians must
be aware of patients complaining of painless visual loss in this high risk group,
as control of blood pressure may be the most important factor in prevention of
this visually devastating condition.
PMID- 25852915
TI - Membranoproliferative glomerulonephritis and Pott's disease.
AB - The reports of glomerular lesions of kidney due to tuberculosis are sparse. A 48
year-old gentleman, presented with swelling of feet of 3 months duration. As he
had renal impairment, proteinuria and normal-sized kidneys, he was subjected to
renal biopsy. The light microscopy and immunofluorescence revealed the diagnosis
was membrano-proliferative glomerulonephritis. During hospital stay, the patient
complained fever and stiffness at thoracic spine. The MRI of thoraco-lumbo-sacral
spine revealed paravertebral abscess at D11-D12. The pus aspirated was positive
for Mycobacterium tuberculosis. He was started on anti-tuberculous medication.
After 8 weeks of therapy, the serum creatinine was 1.5 mg/dL and 24 h urine
protein 250 mg.
PMID- 25852916
TI - Neurofibromatosis type 1-associated hypertension secondary to coarctation of the
thoracic aorta.
AB - Neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's disease, is
an autosomal dominant genetic disorder. NF-I vasculopathy has been used to
describe various vascular malformations associated with NF-1. Secondary
hypertension related to NF-1 vasculopathy has been reported because of renal
artery stenosis, coarctation of the abdominal aorta and other vascular lesions;
however, coarctation of the thoracic aorta has seldom been reported. We report
the first case, to our knowledge, of isolated coarctation of thoracic aorta in a
pregnant female with NF-1. Healthcare providers caring for patients with NF-1
should be aware of associated vascular complications.
PMID- 25852917
TI - Long-term outcome of kidney transplantation in a patient with coexisting
lipoprotein glomerulopathy and fibrillary glomerulonephritis.
AB - Both lipoprotein glomerulopathy (LPG) and fibrillary glomerulonephritis (FGN) are
rare causes of end-stage renal disease (ESRD), and the literature concerning the
outcome of kidney transplant in patients with LPG or FGN is scarce. We report a
patient who suffered from ESRD with coexisting FGN and LPG and received deceased
kidney transplant >10 years ago did not reveal any clinical features of disease
recurrence during follow-up. Our case shows that the prognosis of patients with
LPG component who received kidney transplant can be good. Kidney transplantation
remains a viable therapeutic option for patients with ESRD secondary to FGN with
LPG.
PMID- 25852918
TI - Necrotizing pancreatitis due to hypercalcemia in a hemodialysis patient with
pica.
AB - Pica refers to the persistent, compulsive craving for and ingestion of nonfood
items and certain food items. Pica is quite common among dialysis patients. The
nutrient composition of some of the substances ingested may contribute to severe
metabolic and mineral disturbances and other serious medical complications. We
report the first case of a hemodialysis patient with chalk pica associated
hypercalcemia who developed acute necrotizing pancreatitis. Hydration,
nutritional support and hemodialysis treatments with low-calcium bath led to
clinical improvement and correction of his calcium. This case illustrates the
dangers of pica in dialysis patients and describes modalities of treatment and
detection of this high risk behavior.
PMID- 25852919
TI - Erdheim-Chester disease and knee pain in a dialysis patient.
AB - Erdheim-Chester disease is a rare inflammatory condition characterized by a non
Langerhans histiocytic infiltration, involving the skeleton, nervous system,
viscera, retroperitoneum and elsewhere. The aetiology is unknown. Positron
emission tomography shows areas of involvement. We managed a dialysis patient
with knee pain; a bone marrow specimen showed typical CD68 positive, but CD1a
negative cells. We initiated interferon-alpha therapy although other options
remain open. In our patient, the simultaneous presence of secondary
hyperparathyroidism with tumorous calcifications provided an interesting
additional differential diagnostic possibility regarding skeletal pain.
PMID- 25852920
TI - Exudative detachment as a masquerader in hypoalbuminaemic patients.
PMID- 25852921
TI - Asymptomatic proteinuria, renal cysts and dorsal pancreas agenesis.
PMID- 25852922
TI - Polycystic horseshoe kidney: dealing with double trouble.
PMID- 25852923
TI - Mucormycosis with diabetic and lupus nephropathy.
PMID- 25852924
TI - Generalized aneurysmal disease in association with autosomal dominant polycystic
disease.
PMID- 25852925
TI - Uremic frost.
PMID- 25852926
TI - Tubulointerstitial nephritis and uveitis syndrome in an elderly woman.
PMID- 25852927
TI - Spontaneous tumor lysis syndrome in a case of B-cell non-Hodgkin's lymphoma.
PMID- 25852928
TI - Nephrotic syndrome in acute promyelocytic leukemia.
PMID- 25852929
TI - Early Enterococcus-associated acute postinfectious glomerulonephritis after
kidney transplant.
PMID- 25852930
TI - Combined pulmonary venous thromboembolism and renal artery thrombosis in a
patient with non-small cell lung cancer.
PMID- 25852931
TI - Membrane and centrifugal therapeutic plasma exchange: practical difficulties in
anticoagulating the extracorporeal circuit.
PMID- 25852932
TI - Treatment of acute non-anion gap metabolic acidosis.
AB - Acute non-anion gap metabolic acidosis, also termed hyperchloremic acidosis, is
frequently detected in seriously ill patients. The most common mechanisms leading
to this acid-base disorder include loss of large quantities of base secondary to
diarrhea and administration of large quantities of chloride-containing solutions
in the treatment of hypovolemia and various shock states. The resultant acidic
milieu can cause cellular dysfunction and contribute to poor clinical outcomes.
The associated change in the chloride concentration in the distal tubule lumen
might also play a role in reducing the glomerular filtration rate. Administration
of base is often recommended for the treatment of acute non-anion gap acidosis.
Importantly, the blood pH and/or serum bicarbonate concentration to guide the
initiation of treatment has not been established for this type of metabolic
acidosis; and most clinicians use guidelines derived from studies of high anion
gap metabolic acidosis. Therapeutic complications resulting from base
administration such as volume overload, exacerbation of hypertension and
reduction in ionized calcium are likely to be as common as with high anion gap
metabolic acidosis. On the other hand, exacerbation of intracellular acidosis due
to the excessive generation of carbon dioxide might be less frequent than in high
anion gap metabolic acidosis because of better tissue perfusion and the ability
to eliminate carbon dioxide. Further basic and clinical research is needed to
facilitate development of evidence-based guidelines for therapy of this important
and increasingly common acid-base disorder.
PMID- 25852933
TI - Parathyroid gland autotransplantation after total thyroidectomy in surgical
management of hypopharyngeal and laryngeal carcinomas: A case series.
AB - BACKGROUND AND OBJECTIVES: Total thyroidectomy is indicated in most cases with
postcricoid carcinoma, circumferential hypopharyngeal carcinoma and in advanced
laryngeal carcinoma. Persistent hypoparathyroidism is a frequent complication
after total thyroidectomy which is difficult to manage unlike hypothyroidism.
This study was to assess the feasibility of parathyroid gland autotranplantation
after total thyroidectomy in advanced carcinomas and their effectiveness in
preventing persistent hypoparathyroidism. METHODS: This study included 26
patients with hypopharyngeal and laryngeal carcinoma presented to National Cancer
Institute, Cairo University. Total thyroidectomy and total parathyroid gland
excision were performed as a part of adequate oncologic surgical procedure. The
parathyroid glands were identified, resected and stored in iced saline.
Histological confirmation was necessary before implantation into separated muscle
pockets in the anterior forearm muscles. Regular samples were drawn to assess
serum parathormone and calcium levels. RESULTS: All patients experienced
hypocalcaemia within 1-5 days after operation. Only one patient experienced
parathyroid graft failure while the remaining patients were normocalcemic during
follow up after surgery, indicating functioning parathyroid grafts. CONCLUSIONS:
Parathyroid gland autotranplantation is a simple safe technique with high success
rate in preventing persistent hypoparathyroidism after total thyroidectomy in
surgical management of advanced hypopharyngeal and laryngeal carcinomas.
PMID- 25852934
TI - Recurrent lung atelectasis from fibrin plugs as a very early complication of
bronchial thermoplasty: a case report.
AB - BACKGROUND: Bronchial thermoplasty (BT) is a new therapeutic option for severe
refractory asthma not controlled despite high dose inhaled corticosteroids plus
long-acting bronchodilators and omalizumab in selected cases. Risk of pulmonary
atelectasis after BT in severe asthma has been described in literature, but no
details have been reported on the possible mechanisms of the complication. CASE
PRESENTATION: A 49-year-old male with severe uncontrolled asthma was referred to
BT. One hour after the first procedure, acute respiratory failure occurred with
PaO2/FiO2 < 300. A CT scan showed atelectasis of the right lower and middle
lobes. A new bronchoscopy was performed under non-invasive ventilation; the right
lower and middle lobe bronchus were occluded by bronchus-shaped plugs, that were
very difficult to remove despite repeated saline washings and fragmentation with
forceps. The patient had a rapid resolution of respiratory failure. Four weeks
later, 6 hours after the second session of BT, severe bronchospasm occurred with
respiratory failure. Chest X-Ray showed atelectasis of the left lower lobe,
prompting to perform a new flexible bronchoscopy on non-invasive ventilation. The
exam showed again a plug occluding the left lower lobar bronchus, removed with
forceps and washings. The histological analysis of the plugs demonstrated the
massive presence of fibrin with mucus debris, rare Charcot-Leyden crystals,
scattered macrophages, neutrophils, eosinophils and bronchial epithelial cells.
CONCLUSION: The originality of our case report is related to the recurrence of
bronchial plugging with lobar atelectasis within one and five hours respectively,
after two sequential BT procedures. At the histological evaluation the bronchial
plugs appeared very different from the typical mucoid asthma plugs, being
composed prevalently by fibrin. It can be hypothesized that intense thermal
stimulation of the bronchial mucosa may represent a strong boost for inflammation
in susceptible patients, with microvascular alteration induced directly by heat
or through the release of mediators. Although in severe asthma a risk of
atelectasis from the classical asthma mucoid plugs may be expected, the
peculiarity of our case resides in the formation of fibrin plugs whose direct
correlation with BT should be considered.
PMID- 25852935
TI - Co morbidities of Myofascial Neck Pain among Information Technology
Professionals.
AB - OBJECTIVES: The objective of this study was to identify the musculoskeletal co
morbidities of neck pain of myofascial origin among IT professionals. METHODS: A
retrospective report analysis of 5357 IT professionals from various IT companies
in India was conducted. Demographic details, type and intensity of the
musculoskeletal problems, employee feedbacks on status of musculoskeletal health
and physician's diagnosis were analysed. Descriptive statistics were used to
describe the age, gender, body area affected and nature of work. Chi square test
was used to find the association between musculoskeletal co-morbidities and
myofascial neck pain (MNP). RESULTS: The study participants were predominantly
males (71%). 41% of the population used laptops, 35% desktops and 24% both. Neck
pain was the commonest reported symptom, followed by low back, shoulder and arm
pain respectively. Statistical analysis also revealed that low back pain and
shoulder pain, had a significant association with neck pain. Further analysis
revealed that there was a significant association between the presence of MNP and
thoracic outlet syndrome (p < 0.001) and fibromyalgia syndrome (p < 0.001). Other
than the listed co-morbidities, eye strain was also found to be associated with
MNP. CONCLUSIONS: Low back pain and shoulder pain was found to be co morbid
symptoms noted among IT professionals with MNP. Thoracic outlet syndrome and
fibromyalgia were found to be the most commonly associated disorders with MNP
among IT professionals.
PMID- 25852936
TI - Musculoskeletal disorders of the upper extremities due to extensive usage of hand
held devices.
AB - OBJECTIVE: The use of hand held devices (HHD) such as mobile phones, game
controls, tablets, portable media players and personal digital assistants have
increased dramatically in past decade. While sending a text message or using the
controls of the HHD the users need to use their thumb and other palm muscles
extensively. The objective of this study was to describe the risk factors and
clinical features of the musculoskeletal disorders (MSDs) arising due to usage of
hand held devices and to evaluate the effectiveness of a sequenced rehabilitation
protocol. METHODS: A retrospective report analysis of 70 subjects, who were
diagnosed to have a MSD affecting the upper extremities, was conducted. Medical
charts from a tertiary level rehabilitation centre from 2005-2013 were analysed.
All the subjects reported pain in their upper extremities following extensive
usage of HHD and were examined and diagnosed to have a MSD by an orthopaedic and
rehabilitation physician. After the assessment and diagnosis, all the patients
underwent rehabilitation using a sequenced protocol. RESULTS: All the subjects
reported pain in the thumb and forearm with associated burning, numbness and
tingling around the thenar aspect of the hand, and stiffness of wrist and hand.
43 subjects had symptoms on the right side; 9 on left and 18 had bilateral
symptoms. Correlation was found between hand dominance and MSD. 33 subjects
complained of onset of symptoms following extensive text messaging. All the
subjects were diagnosed to have tendinosis of Extensor Pollicis Longus and
Myofascial Pain Syndrome affecting the 1st interossei, thenar group of muscles
and Extensor Digitorum Communis. 23 of the subjects were senior executives, among
these 7 were CEO's of major multinational companies in India. All the subjects
recovered completely following the rehabilitation. CONCLUSIONS: The study
concluded that mobile phones and gadgets that promoted the predominant usage of
thumb or only one finger while texting or using the controls were associated with
a higher prevalence of MSDs. Treatment using a sequenced rehabilitation protocol
was found to be effective.
PMID- 25852937
TI - Relationship between Psychosocial Risk Factors and Work-Related Musculoskeletal
Disorders among Public Hospital Nurses in Malaysia.
AB - OBJECTIVE: This study examined the relationships between psychosocial work
factors and risk of WRMSDs among public hospital nurses in the Klang Valley,
Malaysia. METHODS: We conducted a cross-sectional study among 660 public hospital
nurses. A self-administered questionnaire was used to collect data on the
occurrence of WRMSDs according to body regions, socio-demographic profiles,
occupational information and psychosocial risk factors. 468 questionnaires were
returned (response rate of 71%), and 376 questionnaires qualified for subsequent
analysis. Univariate analyses were applied to test for mean and categorical
differences across the WRMSDs; multiple logistic regression was applied to
predict WRMSDs based on the Job Strain Model's psychosocial risk factors.
RESULTS: Over two thirds of the sample of nurses experienced discomfort or pain
in at least one site of the musculoskeletal system within the last year. The neck
was the most prevalent site (48.94%), followed by the feet (47.20%), the upper
back (40.69%) and the lower back (35.28%). More than 50% of the nurses complained
of having discomfort in region one (neck, shoulders and upperback) and region
four (hips, knees, ankles, and feet). The results also revealed that
psychological job demands, job strain and iso-strain ratio demonstrated
statistically significant mean differences (p < 0.05) between nurses with and
without WRMSDs. According to univariate logistic regression, all psychosocial
risk factors illustrated significant association with the occurrence of WRMSDs in
various regions of the body (OR: 1.52-2.14). Multiple logistic regression showed
all psychosocial risk factors were significantly associated with WRMSDs across
body regions (OR: 1.03-1.19) except for region 1 (neck, shoulders and upper back)
and region 4 (hips, knees, ankles, and feet). All demographic variables except
for years of employment were statistically and significantly associated with
WRMSDs (p < 0.05). CONCLUSIONS: The findings indicated the high prevalence of
WRMSDs in many body regions, and the risks of developing WRMSDs according to the
various body regions were associated with important psychosocial risk factors
based on the job strain model. These findings have implications for the
management of WRMSDs among public hospital nurses in the Klang Valley, Malaysia.
PMID- 25852938
TI - Effect of Long Working Hours on Self-reported Hypertension among Middle-aged and
Older Wage Workers.
AB - OBJECTIVES: Many studies have reported an association between overwork and
hypertension. However, research on the health effects of long working hours has
yielded inconclusive results. The objective of this study was to identify an
association between overtime work and hypertension in wage workers 45 years and
over of age using prospective data. METHODS: Wage workers in Korea aged 45 years
and over were selected for inclusion in this study from among 10,254 subjects
from the Korean Longitudinal Study of Ageing. Workers with baseline hypertension
and those with other major diseases were excluded. In the end, a total of 1,079
subjects were included. A Cox proportional hazards model was used to calculate
hazard ratios and adjust for baseline characteristics such as sex, age,
education, income, occupation, form of employment, body mass index, alcohol
habit, smoking habit, regular exercise, and number of working days per week.
Additional models were used to calculate hazard ratios after gender
stratification. RESULTS: Among the 1,079 subjects, 85 workers were diagnosed with
hypertension during 3974.2 person-months. The average number of working hours per
week for all subjects was 47.68. The proportion of overtime workers was 61.0%
(cutoff, 40 h per week). Compared with those working 40 h and less per week, the
hazard ratio of subjects in the final model, which adjusted for all selected
variables, working 41-50 h per week was 2.20 (95% confidence interval [CI], 1.19
4.06), that of subjects working 51-60 h per week was 2.40 (95% CI, 1.07-5.39),
and that of subjects working 61 h and over per week was 2.87 (95% CI, 1.33-6.20).
In gender stratification models, the hazard ratio of the females tended to be
higher than that of the males. CONCLUSION: As the number of working hours per
week increased, the hazard ratio for diagnosis of hypertension significantly
increased. This result suggests a positive association between overtime work and
the risk of hypertension.
PMID- 25852939
TI - Vitamin D status and associated occupational factors in Korean wage workers: data
from the 5th Korea national health and nutrition examination survey (KNHANES 2010
2012).
AB - OBJECTIVES: Vitamin D deficiency is increasing worldwide. However, few studies
have attempted to examine the vitamin D status of wage workers and the
correlation between vitamin D deficiency and working conditions. Hence, we aimed
to evaluate the prevalence of vitamin D deficiency and the association between
occupational conditions and vitamin D deficiency among Korean wage workers.
METHODS: Wage workers aged 20-65 years from the 5th Korea National Health and
Nutrition Examination Survey (KNHANES 2010-2012; n = 5409) were included in our
analysis. We measured the prevalence of vitamin D deficiency and identified the
correlations with the working conditions of these subjects. RESULTS: The
prevalence of vitamin D deficiency in male and female subjects was 69.5% and
83.1%, respectively. Among the male subjects, a significant correlation between
vitamin D deficiency and working conditions was observed among shift workers,
office workers, and permanent workers. No significant correlation with any type
of working conditions was observed among female subjects. CONCLUSION: The
prevalence of vitamin D deficiency among Korean wage workers was very high and
was found to correlate significantly with working conditions, likely because of
insufficient exposure to sunlight associated with certain types of work. Wage
workers require more frequent outdoor activity and nutrition management to
maintain sufficient vitamin D level.
PMID- 25852940
TI - Acute health effects of accidental chlorine gas exposure.
AB - OBJECTIVES: This study was conducted to report the course of an accidental
release of chlorine gas that occurred in a factory in Gumi-si, South Korea, on
March 5, 2013. We describe the analysis results of 2 patients hospitalized
because of chlorine-induced acute health problems, as well as the clinical
features of 209 non-hospitalized patients. METHODS: We analyzed the medical
records of the 2 hospitalized patients admitted to the hospital, as well as the
medical records and self-report questionnaires of 209 non-hospitalized patients
completed during outpatient treatment. RESULTS: Immediately after the exposure,
the 2 hospitalized patients developed acute asthma-like symptoms such as cough
and dyspnea, and showed restrictive and combined pattern ventilatory defects on
the pulmonary function test. The case 1 showed asthma-like symptoms over six
months and diurnal variability in peak expiratory flow rate was 56.7%. In case 2,
his FEV1 after treatment (93%) increased by 25% compared to initial FEV1 (68%).
Both cases were diagnosed as chlorine-induced reactive airways dysfunction
syndrome (RADS) on the basis of these clinical features. The most frequent chief
complaints of the 209 non-hospitalized patients were headache (22.7%), followed
by eye irritation (18.2%), nausea (11.2%), and sore throat (10.8%), with
asymptomatic patients accounting for 36.5%. The multiple-response analysis of
individual symptom revealed headache (42.4%) to be the most frequent symptom,
followed by eye irritation (30.5%), sore throat (30.0%), cough (29.6%), nausea
(27.6%), and dizziness (27.3%). CONCLUSIONS: The 2 patients hospitalized after
exposure to chlorine gas at the leakage site showed a clinical course
corresponding to RADS. All of the 209 non-hospitalized patients only complained
of symptoms of the upper airways and mucous membrane irritation.
PMID- 25852941
TI - The association between concealing emotions at work and medical utilization in
Korea.
AB - OBJECTIVES: We aimed to investigate the association between concealing emotions
at work and medical utilization. METHODS: Data from the 2007-2009 4th Korea
National Health and Nutrition Examination Survey (KNHANES IV) was used, 7,094
participants (3,837 males, 3,257 females) aged between 20 and 54 who were
economically active and completed all necessary questionnaire items were
included. Odds ratios (ORs) and 95% confidence intervals (95% CI) for differences
in hospitalization, outpatient visits, and pharmaceutical drug use between those
who concealed their emotions and those who did not were investigated using
logistic regression models with and without gender stratification. RESULTS: Among
those who concealed their emotions (n = 2,763), 47.4% were females, and 50.1% had
chronic disease. In addition, 9.7% of the concealing emotions group had been
hospitalized within the last year, 24.8% had been outpatients in the last two
weeks, and 28.3% had used pharmaceutical drugs in the last two weeks. All ORs
represent the odds of belonging to the concealing emotions group over the non
concealing emotions group. After adjustment for individual, occupational,
socioeconomic and disease factors, the adjusted ORs (95% CI) in hospitalization
are 1.29 (1.08 ~ 1.53) in the total population, 1.25 (0.98 ~ 1.60) in males and
1.30 (1.02 ~ 1.66) in females, in outpatient visits are 1.15 (1.02 ~ 1.29) in the
total population, 1.05 (0.88 ~ 1.24) in males and 1.25 (1.06 ~ 1.47) in females
and in pharmaceutical drug use are 1.12 (1.01 ~ 1.25) in the total population,
1.08 (0.92 ~ 1.27) in males and 1.14 (0.98 ~ 1.33) in females. CONCLUSIONS: Those
who concealed their emotions at work were more likely to use medical services.
Moreover, the health effects of concealing emotions at work might be more
detrimental in women than in men.
PMID- 25852942
TI - Presenteeism among self-employed workers: Korean working conditions survey.
AB - OBJECTIVE: Presenteeism has become a public concern recently. Thus, we aimed to
understand the relationship between self-employed workers and presenteeism using
a nationally representative sample of Korean workers. METHODS: Using data from
the Korean Working Conditions Survey conducted in 2011, a total of 43,392 workers
including paid employees and self-employed workers were analyzed. The effect of
employment status on presenteeism was analyzed using logistic regression
analysis. The independent variables were socioeconomic characteristics, working
conditions, and working environments. RESULTS: Among the 43,392 workers, 34,783
were paid and 8,609 were self-employed. Self-employed workers were more likely to
exhibit presenteeism than were paid workers. An elevated odds ratio of 1.27 (95%
CI 1.19-1.36) was found for presenteeism among self-employed workers. CONCLUSION:
Being self-employed was significantly related with exhibiting presenteeism.
Additional research should investigate whether other factors mediate the
relationship between employment status and presenteeism as well as ways to reduce
presenteeism among self-employed workers.
PMID- 25852943
TI - Workers' experiences with compensated sick leave due to musculoskeletal disorder:
a qualitative study.
AB - OBJECTIVES: The most common occupational disease that is compensated by
Industrial Accident Compensation Insurance (IACI) in Korea is musculoskeletal
disease (MSD). Although complaints about the workers' compensation system have
been raised by injured workers with MSD, studies that examine workers'
experiences with the Korean system are rare. This paper is a qualitative study
designed to examine injured workers' experiences with the workers' compensation
system in Korea. The aim of this study is to explore the drawbacks of the
workers' compensation system and to suggest ways to improve this system. METHODS:
All workers from an automobile parts factory in Anseong, GyeongGi province who
were compensated for MSD by IACI from January 2003 to August 2013 were invited to
participate. Among these 153 workers, 142 workers completed the study. Semi
structured open-ended interviews and questionnaires were administered by
occupational physicians. The responses of 131 workers were analyzed after
excluding 11 workers, 7 of whom provided incomplete answers and 4 of whom were
compensated by accidental injury. Based on their age, disease, department of
employment, and compensation time, 16 of these 131 workers were invited to
participate in an individual in-depth interview. In-depth interviews were
conducted by one of 3 occupational physicians until the interview contents were
saturated. RESULTS: Injured workers with MSD reported that the workers'
compensation system was intimidating. These workers suffered more emotional
distress than physical illness due to the workers' compensation system. Injured
workers reported that they were treated inadequately and remained isolated for
most of the recuperation period. The compensation period was terminated without
ample guidance or a plan for an appropriate rehabilitation process. CONCLUSIONS:
Interventions to alleviate the negative experiences of injured workers, including
quality control of the medical care institutions and provisions for mental and
psychological care for injured workers, are needed to help injured workers return
to work earlier and more healthy.
PMID- 25852944
TI - The relationship between working condition factors and well-being.
AB - OBJECTIVES: Working conditions can exert influence on the physical, mental, and
even social health of workers. Well-being is an appropriate index for the
evaluation of a person's overall health. This paper investigated the association
between various working conditions and worker's well-being. METHODS: Data from
10,019 interviews were collected from the second wave of the Korean Working
Conditions Survey (2010) conducted by the Korea Occupational Safety and Health
Agency between June and October 2010. The data from 5,995 employed workers were
examined in this study. Well-being was measured through the WHO Five Well-Being
Index (1998 version). Sociodemographic and working conditions were analyzed.
Adjusted odds ratios for well-being were calculated with adjusted
sociodemographic factors, working condition factors, or both. RESULTS: Workers'
well-being was significantly higher when they were satisfied with their working
conditions (OR = 1.656, 95% CI = 1.454-1.885), when their actual working hours
were the same as their anticipated working hours (OR = 1.366, 95% CI: 1.120
1.666) or exceeding less than 10 hours (OR = 1.245, 95% CI: 1.004-1.543), and
when their employment was stable (OR = 1.269, 95% CI: 1.098-1.467). CONCLUSIONS:
This study supports the association between working condition factors and well
being in workers.
PMID- 25852945
TI - Predicting risk of COPD in primary care: development and validation of a clinical
risk score.
AB - OBJECTIVES: To develop and validate a clinical risk score to identify patients at
risk of chronic obstructive pulmonary disease (COPD) using clinical factors
routinely recorded in primary care. DESIGN: Case-control study of patients
containing one incident COPD case to two controls matched on age, sex and general
practice. Candidate risk factors were included in a conditional logistic
regression model to produce a clinical score. Accuracy of the score was estimated
on a separate external validation sample derived from 20 purposively selected
practices. SETTING: UK general practices enrolled in the Clinical Practice
Research Datalink (1 January 2000 to 31 March 2006). PARTICIPANTS: Development
sample included 340 practices containing 15 159 newly diagnosed COPD cases and 28
296 controls (mean age 70 years, 52% male). Validation sample included 2259 cases
and 4196 controls (mean age 70 years, 50% male). MAIN OUTCOME MEASURES: Area
under the receiver operator characteristic curve (c statistic), sensitivity and
specificity in the validation practices. RESULTS: The model included four
variables including smoking status, history of asthma, and lower respiratory
tract infections and prescription of salbutamol in the previous 3 years. It had a
high average c statistic of 0.85 (95% CI 0.83 to 0.86) and yielded a sensitivity
of 63.2% (95% CI 63.1 to 63.3) and specificity 87.4% (95% CI 87.3 to 87.5).
CONCLUSIONS: Risk factors associated with COPD and routinely recorded in primary
care have been used to develop and externally validate a new COPD risk score.
This could be used to target patients for case finding.
PMID- 25852946
TI - The effect of macrobiotic Ma-Pi 2 diet on systemic inflammation in patients with
type 2 diabetes: a post hoc analysis of the MADIAB trial.
AB - INTRODUCTION: Current guidelines for the management of type 2 diabetes (T2D)
emphasize diet as essential therapy. However, the effect of diet on systemic
inflammation remains unclear. We investigated the effects of consuming a
macrobiotic Ma-Pi 2 diet versus a standard recommended diet (control diet) on
markers of inflammation in patients with T2D. METHODS: This was a post hoc
analysis of the MADIAB trial, a 21-day randomized controlled trial conducted in
51 patients (25 males and 26 females) with T2D. Patients were randomized 1:1 to
the Ma-Pi 2 macrobiotic diet or a control diet based on dietary guidelines for
T2D. Biological antioxidant potential of plasma and circulating levels of high
sensitivity C reactive protein, interleukin-6, tumor necrosis factor-alpha, and
insulin-like growth factor-1 were assessed. RESULTS: After 21 days on the Ma-Pi 2
or control diet, markers of inflammation were reduced in both groups. The
antioxidant potential of plasma improved significantly in the Ma-Pi group. A
significant reduction in insulin growth factor-1 was observed in the Ma-Pi group
versus control group (p<0.001). CONCLUSIONS: Findings of this post hoc analysis
demonstrated that the Ma-Pi 2 diet is a safe dietary strategy to reduce levels of
the markers of insulin resistance and inflammation, compared with baseline
values, in the short term. Furthermore, the Ma-Pi 2 diet was superior to the
control diet in reducing insulin growth factor-1 and may be beneficial for
patients with T2D. TRIAL REGISTRATION NUMBER: Current Controlled Trials
ISRCTN10467793.
PMID- 25852947
TI - The role of cardiac biomarkers for predicting left ventricular dysfunction and
cardiovascular mortality in acute exacerbations of COPD.
AB - The presence of cardiovascular comorbidities is frequently associated with poor
outcomes in chronic obstructive pulmonary disease (COPD). No clear role has been
defined for cardiac biomarkers in acute exacerbations of COPD (AECOPD). The aim
of this systematic review was to examine the prognostic value of brain
natriuretic peptide (BNP) and troponins in patients with AECOPD. Two independent
authors searched the PubMed and Cochrane Library to collect clinical trials,
observational studies and meta-analyses studying the prognostic value of cardiac
biomarkers in AECOPD. The reference lists of all the included studies were also
reviewed. A total of 14 studies were included in the review, of which 10 measured
troponins, 7 measured BNP or NT-proBNP, and 3 measured both. Of the studies that
used mortality in AECOPD as an end point, some but not all found that elevated
BNP and/or troponins were associated with increased mortality. Of the studies
that used left ventricular (LV) dysfunction in AECOPD as an end point, all found
a significant association between elevated BNP and troponins in the diagnosis of
LV dysfunction. In summary, it appears that there may be a link between an
elevated level of BNP or NT-proBNP and increased cardiovascular mortality in
AECOPD, although the data currently available are not conclusive. The
inconsistencies in biomarkers measured, time points of measurements and the
variability in outcome measured preclude more robust analysis.
PMID- 25852948
TI - The no-touch vein graft for coronary artery bypass surgery preserves the left
ventricular ejection fraction at 16 years postoperatively: long-term data from a
longitudinal randomised trial.
AB - OBJECTIVES: To assess the left ventricular heart function and the clinical
outcome 16 years after coronary artery bypass surgery. DESIGN: In a randomised
trial, the no-touch (NT) vein graft in coronary artery bypass surgery has shown a
superior patency rate, a slower progression of atherosclerosis and better
clinical outcome compared to the conventional (C) vein graft at 8.5 years. All
patients at mean time 16 years were offered an echocardiographic and clinical
examination. RESULTS: In the NT-group 34 patients and in the C-group 31 patients
underwent an echocardiography examination. A significantly better left ventricle
ejection fraction was seen in the NT-group compared to the C-group (57.9% vs
49.4%; p=0.011). The size of the left atrium in NT was 21.7 cm(2) compared to
23.9 cm(2) in C; p=0.034. No patient in NT had atrial fibrillation compared to
five patients in C (p=0.021). Patients with a brain natriuretic peptide value
(BNP) >=150 was 30% in NT compared to 38% in C. Total mortality was 25% in NT vs
27% in C. Cardiac-related deaths were 8% and 12% in NT and C respectively.
CONCLUSIONS: The NT vein graft preserves the left ventricular ejection fraction
after 16 years. A smaller left atrium, a lower BNP and no atrial fibrillation
indicates an improved diastolic left ventricular function in the NT-group. TRIAL
REGISTRATION: The study is registered with clinicaltrials.gov (NCT01686100) and
The Research and Development registry in Sweden (no. 102841).
PMID- 25852949
TI - Impact of proctoring on success rates for percutaneous revascularisation of
coronary chronic total occlusions.
AB - OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO)
percutaneous coronary intervention (PCI) in six UK centres. METHODS: We
retrospectively analysed 587 CTO procedures from six UK centres and compared
success rates of operators who had received proctorship with success rates of the
same operators before proctorship (pre-proctored) and operators in the same
institutions who had not been proctored (non-proctored). There were 232 patients
in the pre-proctored/non-proctored group and 355 patients in the post-proctored
group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for
each case. RESULTS: CTO PCI success was greater in the post-proctored compared
with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more
complex cases where JCTO>=2, the difference in success was greater (70.7% vs
49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in
centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the
proportion of very difficult cases with JCTO score >=3 increased from 15.3%
(35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an
increase in procedural success for CTO PCI, an increase in complex CTO PCI and an
increase in total CTO PCI activity. Proctoring may be a valuable way to improve
access to CTO PCI and the likelihood of procedural success.
PMID- 25852950
TI - Breathing difficulty in a middle-aged woman - a dangerous cause?
AB - Temporal lobe epilepsy is a rare but treatable cause of apnoea.
PMID- 25852951
TI - The US hospital standardised mortality ratio: Retrospective database study of
Massachusetts hospitals.
AB - OBJECTIVES: To present a case-mix adjustment model that can be used to calculate
Massachusetts hospital standardised mortality ratios and can be further adapted
for other state-wide data-sets. DESIGN: We used binary logistic regression models
to predict the probability of death and to calculate the hospital standardised
mortality ratios. Independent variables were patient sociodemographic
characteristics (such as age, gender) and healthcare details (such as admission
source). Statistical performance was evaluated using c statistics, Brier score
and the Hosmer-Lemeshow test. SETTING: Massachusetts hospitals providing care to
patients over financial years 2005/6 to 2007/8. PATIENTS: 1,073,122 patients
admitted to Massachusetts hospitals corresponding to 36 hospital standardised
mortality ratio diagnosis groups that account for 80% of in-hospital deaths
nationally. MAIN OUTCOME MEASURES: Adjusted in-hospital mortality rates and
hospital standardised mortality ratios. RESULTS: The significant factors
determining in-hospital mortality included age, admission type, primary
diagnosis, the Charlson index and do-not-resuscitate status. The Massachusetts
hospital standardised mortality ratios for acute (non-specialist) hospitals
ranged from 60.3 (95% confidence limits 52.7-68.6) to 130.3 (116.1-145.8). The
reference standard hospital standardised mortality ratio is 100 with the values
below and above 100 suggesting either random or special cause variation. The
model was characterised by excellent discrimination (c statistic 0.87), high
accuracy (Brier statistics 0.03) and close agreement between predicted and
observed mortality rates. CONCLUSIONS: We have developed a case-mix model to give
insight into mortality rates for patients served by hospitals in Massachusetts.
Our analysis indicates that this technique would be applicable and relevant to
Massachusetts hospital care as well as to other US hospitals.
PMID- 25852952
TI - Trends in hospital admissions for Varicella and Zoster viruses in England,
2001/2002-2010/2011: time trend study.
AB - OBJECTIVES: Varicella and Herpes Zoster are common infectious diseases. Various
studies have estimated rates of infection for both manifestations of these
infections; however rates of hospital admissions across the country have not
previously been described. This paper presents data on hospital admissions in
England for Varicella and Herpes Zoster from 2001/2002 to 2010/2011. DESIGN: Time
trends study of all hospital admissions for Varicella and Herpes Zoster from
2001/2002 to 2010/2011 in England. SETTING: Hospital admissions across England
from 2001/2002 to 2010/2011. PARTICIPANTS: We included all patients admitted to
hospital from 2001/2002 to 2010/2011 diagnosed with Varicella and Zoster
according to the International Classification of Diseases version 10 (ICD-10).
MAIN OUTCOME MEASURES: The main outcome measures were admission rates by year and
diagnosis and age-specific admission rates for Varicella and Zoster from
2001/2002 to 2010/2011. METHODS: We analysed data from Hospital Episode
Statistics which include patient characteristics such as age which was used here
in order to standardise rates to the relevant population. We also used mid-year
population estimates from the Office for National Statistics for standardisation
purposes. All analyses were conducted using Stata v12.0. RESULTS: The hospital
admission rate for Varicella cases has risen by 1.8% over the 10-year study
period. While the overall admission rates for Herpes Zoster have decreased by 4%
from 2001/2002 levels. The vast majority of Varicella and Zoster admissions were
not associated with any complications. CONCLUSION: The introduction of Herpes
Zoster vaccine is anticipated to decrease hospital admissions in older age groups
further. A repeat of this study after a further period of time would help to
evaluate the impact of the introduction of Herpes Zoster vaccine in England on
hospital admissions.
PMID- 25852953
TI - The Risotto sign - a severe inflammatory bursitis with rice body formation,
complicating a rotator cuff repair with a bioabsorbable suture anchor.
AB - There is an association between inflammatory bursitis with rice body formation
and use of bioabsorbable suture anchors.
PMID- 25852954
TI - Raised intracranial pressure following abdominal closure in a polytrauma patient.
AB - We report a polytrauma case requiring simultaneous neurosurgery and laparotomy.
Upon abdominal closure, raised intracranial pressure occurred. This illustrates
the important physiological interplay between body compartments in critical care
patients.
PMID- 25852955
TI - The bunkie test: descriptive data for a novel test of core muscular endurance.
AB - The Bunkie test, a functional performance test consisting of 5 test positions
(performed bilaterally), has been used to assess aspects of muscular function.
Current performance measures are based on clinical recommendations. The purpose
of this study was to report normative data for a healthy population. One hundred
and twelve subjects (mean age 25.9 +/- 4.5 years) were recruited from a
university setting. Subjects completed a demographic questionnaire prior to
testing. Hold times for each position was measured in seconds. Subjects were able
to hold many of the positions for a mean score of approximately 40 seconds. There
were no side-to-side differences in test position hold times per gender. Males
were able to hold some positions significantly longer than their female
counterparts. Males with a lower BMI were able to hold 8 of the 10 positions
significantly longer than those with a higher BMI. Bunkie test scores in subjects
with a prior history of musculoskeletal injury were similar to those with no
history of injury. The normative data presented in this study may be used by
rehabilitation professionals when assessing and rehabilitating their patients.
PMID- 25852956
TI - An ovarian pregnancy in a patient with a history of bilateral salpingectomies: a
rare case.
AB - Background. 1 in 200 ectopic pregnancies are true ovarian pregnancies that
fulfill the Spiegelberg criteria. Despite being rare, multiple case reports and
series have been reported. Few cases have been published in which the event was
preceded by salpingectomy. Case. The patient is a 32-year-old female who
presented to the emergency room with abdominal pain. She was found to be
pregnant, despite a history of two previous ectopic pregnancies treated with
salpingectomies. Sonography confirmed a left adnexal mass and free fluid. Surgery
revealed a ruptured ovarian pregnancy which was also confirmed by pathology.
Conclusion. This is a case of an ovarian pregnancy in a patient with two previous
salpingectomies. It underscores the importance of searching for an ectopic
pregnancy in patients with abdominal pain after fertility impairing surgery.
PMID- 25852957
TI - Management of Dysphagia Pre- and Postoperatively in a Case of Eagle's Syndrome.
AB - Eagle's syndrome (ES) is rare condition, most frequently described within the
context of case study presentation. ES results from elongation of the styloid
process, contributing to symptoms such as globus sensation in the throat, as well
as pain localized to the ear, neck, face, or tongue. Additional symptoms can
include hypersalivation, change in vocal quality, submandibular swelling, and
dysphagia. This report discusses evaluation, diagnosis, and surgical intervention
with respect to Eagle's Syndrome in a patient presenting with moderate-severe
dysphagia.
PMID- 25852958
TI - Laparoscopic treatment of a spontaneously ruptured kidney (wunderlich syndrome).
AB - Spontaneous, nontraumatic retroperitoneal hemorrhage or Wunderlich syndrome (WS)
is a rare but potential life-threatening condition. In most patients a bleeding
renal neoplasm is the cause of the retroperitoneal hematoma. The management of
this condition includes a conservative approach in the hemodynamically stable
patients and active treatment in the unstable patients. Active treatment includes
angioembolization or surgery. If angioembolization is not available open surgery
is in most cases the preferred approach. We present a patient with a
spontaneously ruptured kidney due to a central renal angiomyolipoma, which was
treated by laparoscopic nephrectomy.
PMID- 25852959
TI - p40 as a Basal Cell Marker in the Diagnosis of Prostate Glandular Proliferations:
A Comparative Immunohistochemical Study with 34betaE12.
AB - Immunohistochemistry is important for the accurate diagnosis of basal cells in
atypical glandular proliferations of the prostate. p40, an isoform of p63, may be
an adjunct to a marker panel in this setting. Biopsies of 68 patients were
analyzed by immunohistochemistry using antibodies to 34betaE12 and p40. Basal
cell staining was classified as negative, partial (<60%), or diffuse (>=60%);
irregular staining was defined as discordant staining patterns. In acinar
proliferations (N = 41), partial staining for both markers was seen in 42%, and
diffuse staining in 46% of reactive cases. An irregular reactivity was noted in
one case only (2%). Finally, these lesions were signed out as benign. Acinar
proliferations negative for both markers and limited amount of glands (<=4) were
termed atypical small acinar proliferations (ASAP). Out of six PIN lesions two
cases showed partial, three cases showed diffuse reactivity for both markers, and
one case was stained irregular. All cases diagnosed as prostate carcinomas (N =
20) had no evidence of basal cell staining for neither of the markers. p40
expression is closely correlated to 34betaE12 with respect to demonstration of
basal cells of prostate glands and may provide further information on the dignity
of glandular proliferations of the prostate.
PMID- 25852960
TI - Corrigendum to "the studies of chlorogenic Acid antitumor mechanism by gene chip
detection: the immune pathway gene expression".
AB - [This corrects the article DOI: 10.1155/2013/617243.].
PMID- 25852961
TI - Late evaluation of upper limb arterial flow in patients after long radial
(PiCCOTM) catheter placement.
AB - BACKGROUND: The purpose of the study was to assess blood flow in the upper limb
arteries after prolonged catheterization with long radial artery catheters (LRC)
which reach the subclavian artery compared to catheterization with standard short
radial artery catheters (SRC) and a group of upper limb flow without any catheter
placement (NOCATH), with both SRC and NOCATH as control groups. METHODS:
Prospective observational study with 20 patients admitted to ICU (40 upper limbs)
with LRC and/or SRC inserted >48 h for hemodynamic monitoring. More than 45 days
after catheter withdrawal, patients underwent a Doppler ultrasound study of both
upper limbs. Arterial flows of arms with LRC (FlowLRC) were compared with
arterial flows of arms with SRC (FlowSRC) and those without any catheter
(FlowNOCATH). RESULTS: Flow in the ulnar, brachial, and subclavian arteries did
not show any significant difference between the two types of catheters. The only
significant difference was in the radial arteries, showing a lower mean flow in
the arms with LRC than in the arms with SRC (2.2 vs. 8.5 cc/min; p = 0.041). Flow
reduction in the radial artery (74%) in the arms with LRC compared to the SRC
arms showed a tendency to increase ulnar flow as a compensatory mechanism. None
of the patients with LRC included in our study had any ischemic events, in spite
of observing complete flow occlusion in three radial arteries (18%) from the
Doppler study. CONCLUSIONS: In this sample, the use of PiCCO long radial
catheters reaching the subclavian artery did not produce chronic significant
changes in brachial or subclavian flows. However, LRC produces a significant
reduction in radial flow and a tendency to increase ulnar flow. When comparing
these blood flow changes with those produced by SRC use, only the radial flow
reduction was significantly lower, whereas the other arterial flow changes did
not significantly differ.
PMID- 25852962
TI - End-tidal carbon dioxide monitoring using a naso-buccal sensor is not appropriate
to monitor capnia during non-invasive ventilation.
AB - BACKGROUND: In acute respiratory failure, arterial blood gas analysis (ABG) is
used to diagnose hypercapnia. Once non-invasive ventilation (NIV) is initiated,
ABG should at least be repeated within 1 h to assess PaCO2 response to treatment
in order to help detect NIV failure. The main aim of this study was to assess
whether measuring end-tidal CO2 (EtCO2) with a dedicated naso-buccal sensor
during NIV could predict PaCO2 variation and/or PaCO2 absolute values. The
additional aim was to assess whether active or passive prolonged expiratory
maneuvers could improve the agreement between expiratory CO2 and PaCO2. METHODS:
This is a prospective study in adult patients suffering from acute hypercapnic
respiratory failure (PaCO2 >= 45 mmHg) treated with NIV. EtCO2 and expiratory CO2
values during active and passive expiratory maneuvers were measured using a
dedicated naso-buccal sensor and compared to concomitant PaCO2 values. The
agreement between two consecutive values of EtCO2 (delta EtCO2) and two
consecutive values of PaCO2 (delta PaCO2) and between PaCO2 and concomitant
expiratory CO2 values was assessed using the Bland and Altman method adjusted for
the effects of repeated measurements. RESULTS: Fifty-four datasets from a
population of 11 patients (8 COPD and 3 non-COPD patients), were included in the
analysis. PaCO2 values ranged from 39 to 80 mmHg, and EtCO2 from 12 to 68 mmHg.
In the observed agreement between delta EtCO2 and deltaPaCO2, bias was -0.3 mmHg,
and limits of agreement were -17.8 and 17.2 mmHg. In agreement between PaCO2 and
EtCO2, bias was 14.7 mmHg, and limits of agreement were -6.6 and 36.1 mmHg.
Adding active and passive expiration maneuvers did not improve PaCO2 prediction.
CONCLUSIONS: During NIV delivered for acute hypercapnic respiratory failure,
measuring EtCO2 using a dedicating naso-buccal sensor was inaccurate to predict
both PaCO2 and PaCO2 variations over time. Active and passive expiration
maneuvers did not improve PaCO2 prediction. TRIAL REGISTRATION:
ClinicalTrials.gov: NCT01489150.
PMID- 25852964
TI - Failed noninvasive positive-pressure ventilation is associated with an increased
risk of intubation-related complications.
AB - BACKGROUND: Noninvasive positive-pressure ventilation (NIPPV) use has increased
in the treatment of patients with respiratory failure. However, despite
decreasing the need for intubation in some patients, there are no data regarding
the risk of intubation-related complications associated with delayed intubation
in adult patients who fail NIPPV. The objective of this study is to evaluate the
odds of a composite complication of intubation following failed NIPPV compared to
patients intubated primarily in the medical intensive care unit (ICU). METHODS:
This is a single-center retrospective cohort study of 235 patients intubated
between 1 January 2012 and 30 June 2013 in a medical ICU of a university medical
center. A total of 125 patients were intubated after failing NIPPV, 110 patients
were intubated without a trial of NIPPV. Intubation-related data were collected
prospectively through a continuous quality improvement (CQI) program and
retrospectively extracted from the medical record on all patients intubated on
the medical ICU. A propensity adjustment for the factors expected to affect the
decision to initially use NIPPV was used, and the adjusted multivariate
regression analysis was performed to evaluate the odds of a composite
complication (desaturation, hypotension, or aspiration) with intubation following
failed NIPPV versus primary intubation. RESULTS: A propensity-adjusted
multivariate regression analysis revealed that the odds of a composite
complication of intubation in patients who fail NIPPV was 2.20 (CI 1.14 to 4.25),
when corrected for the presence of pneumonia or acute respiratory distress
syndrome (ARDS), and adjusted for factors known to increase complications of
intubation (total attempts and operator experience). When a composite
complication occurred, the unadjusted odds of death in the ICU were 1.79 (95% CI
1.03 to 3.12). CONCLUSIONS: After controlling for potential confounders, this
propensity-adjusted analysis demonstrates an increased odds of a composite
complication with intubation following failed NIPPV. Further, the presence of a
composite complication during intubation is associated with an increased odds of
death in the ICU.
PMID- 25852963
TI - Sleeping on a problem: the impact of sleep disturbance on intensive care patients
- a clinical review.
AB - Sleep disturbance is commonly encountered amongst intensive care patients and has
significant psychophysiological effects, which protract recovery and increases
mortality. Bio-physiological monitoring of intensive care patients reveal
alterations in sleep architecture, with reduced sleep quality and continuity. The
etiological causes of sleep disturbance are considered to be multifactorial,
although environmental stressors namely, noise, light and clinical care
interactions have been frequently cited in both subjective and objective studies.
As a result, interventions are targeted towards modifiable factors to ameliorate
their impact. This paper reviews normal sleep physiology and the impact that
sleep disturbance has on patient psychophysiological recovery, and the
contribution that the clinical environment has on intensive care patients' sleep.
PMID- 25852965
TI - Development and usability testing of a Web-based decision aid for families of
patients receiving prolonged mechanical ventilation.
AB - BACKGROUND: Web-based decision aids are increasingly important in medical
research and clinical care. However, few have been studied in an intensive care
unit setting. The objectives of this study were to develop a Web-based decision
aid for family members of patients receiving prolonged mechanical ventilation and
to evaluate its usability and acceptability. METHODS: Using an iterative process
involving 48 critical illness survivors, family surrogate decision makers, and
intensivists, we developed a Web-based decision aid addressing goals of care
preferences for surrogate decision makers of patients with prolonged mechanical
ventilation that could be either administered by study staff or completed
independently by family members (Development Phase). After piloting the decision
aid among 13 surrogate decision makers and seven intensivists, we assessed the
decision aid's usability in the Evaluation Phase among a cohort of 30 surrogate
decision makers using the Systems Usability Scale (SUS). Acceptability was
assessed using measures of satisfaction and preference for electronic
Collaborative Decision Support (eCODES) versus the original printed decision aid.
RESULTS: The final decision aid, termed 'electronic Collaborative Decision
Support', provides a framework for shared decision making, elicits relevant
values and preferences, incorporates clinical data to personalize prognostic
estimates generated from the ProVent prediction model, generates a printable
document summarizing the user's interaction with the decision aid, and can
digitally archive each user session. Usability was excellent (mean SUS, 80 +/-
10) overall, but lower among those 56 years and older (73 +/- 7) versus those who
were younger (84 +/- 9); p = 0.03. A total of 93% of users reported a preference
for electronic versus printed versions. CONCLUSIONS: The Web-based decision aid
for ICU surrogate decision makers can facilitate highly individualized
information sharing with excellent usability and acceptability. Decision aids
that employ an electronic format such as eCODES represent a strategy that could
enhance patient-clinician collaboration and decision making quality in intensive
care.
PMID- 25852966
TI - Immunoglobulin Resistance in Kawasaki Disease.
AB - Background: The aim of this study was to identify risk factors for immunoglobulin
resistance, including clinical symptoms such as arthritis and the pH of
intravenous immunoglobulin. Methods: The data of children with Kawasaki disease
who had received immunoglobulin were evaluated. Data regarding the brand of
immunoglobulin administered were abstracted from the pharmacy records. Results:
Eighty consecutive children with Kawasaki disease were evaluated (Mdnage=28
months, 66% male). The prevalence of immunoglobulin resistance was 30%. Arthritis
was a presenting symptom in the acute phase of Kawasaki disease in 8% (6/80, all
male) and was seen in significant association with immunoglobulin resistance in
comparison to those without arthritis (16.7% vs. 0.2%, p=0.008). Next, the
immunoglobulin brand types were divided into two groups: the relatively high pH
group (n=16), including Carimune (pH 6.6+/-0.2), and the low pH group (n=63),
including Gamunex (pH 4-4.5) or Privigen (pH 4.6-5). Overall, no significant
difference in immunoglobulin responsiveness was found between the low pH and the
high pH groups (73% vs. 56%, p=0.193), although the low pH group showed a trend
toward a larger decrease in erythrocyte sedimentation rate (p=0.048), lower
steroid use (p=0.054), and lower coronary involvement (p=0.08) than those in the
high pH group. Conclusions: Children presenting with arthritis in the acute phase
of Kawasaki disease may be at risk for immunoglobulin resistance.
PMID- 25852967
TI - The Impact of Parent's Health Literacy on Pediatric Asthma Outcomes.
AB - Background: Health literacy has been associated with health disparities in many
disease outcomes, including children's asthma. Parents are responsible for most
of children's healthcare. Therefore, parents' health literacy may impact
children's health outcomes, including asthma control. This study sought to
determine the association between parent health literacy and children's asthma
control among a cohort of predominately minority urban children aged between 6
and 12 years. Methods: This cross-sectional study assessed children with asthma
and their parents at a single outpatient visit. English-speaking parents and
their children, aged between 6 and 12 years with physician-diagnosed asthma, were
eligible for this study. Healthcare providers assessed asthma control and
severity, and parents completed demographic, health literacy, asthma control, and
asthma knowledge measures. Children completed a pulmonary function test as part
of the Asthma Control Questionnaire (ACQ) scoring. Results: A total of 281 parent
child dyads provided data, with the majority of parents being mothers and African
American, with a high school level education or less. Lower parent health
literacy was associated with worse asthma control as rated both by the provider
(p=0.007) and the ACQ (p=0.013), despite only moderate concordance between
ratings (rho=0.408, p<0.0001). Lower parent health literacy also was associated
with less asthma knowledge, which was associated with worse asthma control.
Conclusions: Higher parent health literacy was associated with more parent asthma
knowledge and better child asthma control. Pediatric providers should consider
tailoring education or treatment plans or utilizing universal precautions for low
health literacy.
PMID- 25852969
TI - Vitamin D and Asthma: Association, Causality, or Intervention?
AB - Many observational studies have investigated the potential association between
vitamin D and asthma. However, it is difficult to find a temporal causal
relationship in cross-sectional or observational studies. This review presents
recent clinical trials and the evidence of association between vitamin D and
asthma in different patient populations and asthma status. Well-designed clinical
trials are warranted in order to define the optimal level of vitamin D, as well
as dosing and duration of vitamin D supplementation, in pediatric patients.
PMID- 25852968
TI - Median Household Income: Association with Mortality in Children on Chronic
Ventilation at Home Secondary to Bronchopulmonary Dysplasia.
AB - Objective: The aim of this study was to determine if living in a lower income
neighborhood is associated with mortality of patients with bronchopulmonary
dysplasia (BPD) on home ventilation. Methods: Patients were divided into two
groups by their ZIP code-based annual household income (Z-AHI), their year of
birth, and the median state household income. Survival, liberation from
ventilation, and decannulation rates were analyzed between the groups. Results:
Over 27 years, 94 patients met our inclusion criteria: 58 (61.7%) were in the
group with lower Z-AHI, and 36 (38.3%) were in the group with the Z-AHI above the
median state household. Of the patients who died, 14/15 were in the lower Z-AHI
group (p=0.003). Survival probability at 60 months of age showed no significant
difference between the two groups: 81% [95% CI 70.9, 91.1] for the group with the
Z-AHI below the median state household, and 100% [95% CI 100.0, 90.3] for the
group with higher Z-AHI (p=0.31). Conclusions: The results of this study are
descriptive, as the cause of the association between mortality rate and living in
an area with lower household income is not yet understood. The difference in
mortality rates between groups above and below the median state income suggests a
serious health disparity, which warrants further study. Additional understanding
of this effect requires more complete and direct measurement of socioeconomic
status and individual characteristics, and better understanding of local
environmental conditions.
PMID- 25852970
TI - Teenage and Young Adult Cancer-Related Fatigue Is Prevalent, Distressing, and
Neglected: It Is Time to Intervene. A Systematic Literature Review and Narrative
Synthesis.
AB - PURPOSE: Cancer-related fatigue in adults has been the subject of considerable
recent research, confirming its importance as a common and debilitating symptom,
and establishing a number of evidence-based interventions. There has, however,
been limited focus on the fatigue suffered by teenagers and young adults with
cancer, a group recognized as having unique experiences and developmental needs.
We have undertaken a systematic review of the literature to provide a
comprehensive overview of studies evaluating fatigue in this younger patient
group in order to guide clinical practice and future research. METHOD: We
searched MEDLINE, EMBASE, PsycINFO, and CINAHL databases for literature
containing data relating to any aspect of fatigue in patients aged 13-24 at
cancer diagnosis or treatment. RESULTS: Sixty articles were identified, of which
five described interventional clinical trials. Cancer-related fatigue was
consistently one of the most prevalent, severe, and distressing symptoms, and it
persisted long-term in survivors. It was associated with a number of factors,
including poor sleep, depression, and chemotherapy. There was little evidence for
the effectiveness of any intervention, although exercise appears to be the most
promising. Importantly, fatigue was itself a significant barrier to physical and
social activities. CONCLUSION: Cancer-related fatigue is a major and disabling
problem in young cancer patients. Effective management strategies are needed to
avoid compounding the dependence and social isolation of this vulnerable patient
group. Future research should focus on providing evidence for the effectiveness
of interventions, of which activity promotion and management of concurrent
symptoms are the most promising.
PMID- 25852971
TI - Family Functioning Mediates the Association Between Neurocognitive Functioning
and Health-Related Quality of Life in Young Adult Survivors of Childhood Brain
Tumors.
AB - PURPOSE: Childhood brain tumor (BT) survivors experience significant
neurocognitive sequelae that affect health-related quality of life (HRQOL). A
model of neurodevelopmental late effects and family functioning in childhood
cancer survivors suggests associations between survivor neurocognitive
functioning, family functioning, and survivor HRQOL. This study examines the
concurrent associations between survivor neurocognitive functioning, family
functioning, and survivor emotional HRQOL, and the indirect effects of
neurocognitive functioning on survivor emotional HRQOL through family
functioning. METHODS: Participants included young adult-aged childhood BT
survivors (18-30 years old; N=34) who were on average 16 years post-diagnosis,
and their mothers. A brief neuropsychological battery assessed working and verbal
memory, processing speed, and executive functioning. Survivors and mothers
completed measures of family functioning, and mothers completed a proxy-report
measure of survivor HRQOL. RESULTS: Spearman bivariate correlations examined the
associations between indices of survivor neurocognitive functioning and
concurrent family functioning and survivor emotional HRQOL. Poorer survivor
processing speed, working memory, verbal memory, and executive function were
significantly associated with worse survivor- and mother-reported family
functioning (r's range: 0.36-0.58). Additionally, worse survivor processing speed
and executive function were significantly associated with poorer survivor
emotional HRQOL (r's range: 0.44-0.48). Bootstrapping analyses provided evidence
for the indirect effects of neurocognitive functioning on survivor emotional
HRQOL through family functioning. CONCLUSION: These findings suggest that family
functioning is an important variable that might mitigate the negative influence
of neurocognitive late effects on survivors and is a potential target in future
interventions.
PMID- 25852973
TI - Suicide attempts among men and women with partner violence according to
borderline personality status.
PMID- 25852974
TI - Multimodal approach to identifying malingered posttraumatic stress disorder: a
review.
AB - The primary aim of this article is to aid clinicians in differentiating true
posttraumatic stress disorder from malingered posttraumatic stress disorder.
Posttraumatic stress disorder and malingering are defined, and prevalence rates
are explored. Similarities and differences in diagnostic criteria between the
fourth and fifth editions of the Diagnostic and Statistical Manual of Mental
Disorders are described for posttraumatic stress disorder. Possible motivations
for malingering posttraumatic stress disorder are discussed, and common
characteristics of malingered posttraumatic stress disorder are described. A
multimodal approach is described for evaluating posttraumatic stress disorder,
including interview techniques, collection of collateral data, and psychometric
and physiologic testing, that should allow clinicians to distinguish between
those patients who are truly suffering from posttraumatic disorder and those who
are malingering the illness.
PMID- 25852972
TI - Exploring Mediators of Physical Activity in Young Adult Cancer Survivors:
Evidence from a Randomized Trial of a Facebook-Based Physical Activity
Intervention.
AB - PURPOSE: This study examined the effects of a physical activity (PA) intervention
for young adult cancer survivors on changes in self-efficacy, social support, and
self-monitoring and determined whether changes in these social cognitive theory
constructs mediated the relationship between the intervention and changes in PA.
METHODS: A 12-week randomized trial compared a Facebook-based intervention
(FITNET) aimed at increasing moderate-to-vigorous intensity PA to a Facebook
based self-help comparison group. Young adult cancer survivors (N=86, aged 21-39)
were randomly assigned to one of the two groups. Self-report measures of PA and
psychosocial variables were collected at baseline and after 12 weeks. RESULTS:
The FITNET group reported lower self-efficacy for sticking to exercise (mean
change=-0.38; 95% CI: -0.62 to -0.12; p=0.025) and social support from friends on
social networking websites (mean change=-0.47; 95% CI: -1.45 to 0.65; p=0.039)
relative to the self-help comparison group over time. Changes in social support
from friends on social networking websites partially mediated the intervention
effects on moderate-to-vigorous PA (mean indirect effect=-22.4; 95% CI: -62.0 to
2.8) in the unexpected direction. Across both groups, social support from friends
and self-monitoring were positively associated with changes in moderate-to
vigorous PA. CONCLUSION: The proposed mediators did not explain the positive
effects of the FITNET intervention on mild PA. The lack of significant
improvements in psychosocial constructs among FITNET participants may partly
explain why the intervention did not increase moderate-to-vigorous PA relative to
the self-help comparison group. Future PA interventions with young adult cancer
survivors should examine targeting social support from friends and self
monitoring.
PMID- 25852975
TI - Lurasidone: a new treatment option for bipolar depression-a review.
AB - Depressive episodes in bipolar disorder contribute to significant morbidity and
mortality. Until recently, only quetiapine and an olanzapine-fluoxetine
combination were approved to treat bipolar depression. Recently, lurasidone was
approved to treat bipolar depression either as monotherapy or adjunctively with
lithium or valproate. Lurasidone was well- tolerated, and commonly observed
adverse reactions (incidence >=5% and at least twice the rate for placebo) were
akathisia, extrapyramidal symptoms, and somnolence. There were no significant
metabolic or electrocardiogram abnormalities. It is taken with food to ensure
maximal absorption, and dose should be adjusted in patients who receive moderate
CYP450 inhibitors or inducers and in patients with renal disease.
PMID- 25852976
TI - Functional cortical and cerebellar reorganization in a case of moyamoya disease.
AB - BACKGROUND: Functional studies have been previous reported in stroke patients,
but no studies of functional magnetic resonance imaging have been performed in
Moyamoya disease. OBJECTIVE: To assess the cortical and cerebellar reorganization
in a moyamoya patient. METHODS: We reported a case of a patient suffering from
moyamoya disease, undergoing a neuropsychological assessment, a neurocognitive
rehabilitative treatment, an electroencephalogram evaluation, and a functional
magnetic resonance imaging examination. RESULTS: The subject showed a cognitive
impairment, a slow electroencephalogram activity, and the ipsi- and controlateral
motor cortex and cerebellar functional magnetic resonance imaging activation.
CONCLUSIONS: This is the first functional magnetic resonance imaging case study
reported in moyamoya disease. We showed a cortical reorganization, which could
play an important role in clinical evaluation and motor recovery. The cerebellar
activation, showed after cognitive and motor rehabilitation, could support the
idea that the cerebellum contains several cognitive-related subregions involved
in different functional networks in moyamoya disease.
PMID- 25852977
TI - Use of ketamine in acute cases of suicidality.
AB - Ketamine is an N-methyl-D- aspartate antagonist with rapid antidepressant
effects. Research shows that ketamine has a fast onset of reduction in depressive
symptoms and shows sustained remission of suicidal ideation in some patients.
This article provides a brief review of the literature on the use of ketamine for
depression and in acute cases of suicidality. The authors conclude that, while
further investigation is needed, ketamine may be a useful treatment option for
acute suicidality in emergency room settings.
PMID- 25852978
TI - Workplace bullying: a tale of adverse consequences.
AB - Workplace bullying is defined as the repetitive and systematic engagement of
interpersonally abusive behaviors that negatively affect both the targeted
individual and the work organization. According to the findings of 12 studies,
being bullied in the workplace affects approximately 11 percent of workers.
Victims are frequently blue-collar and unskilled workers. However, there also
appear to be gender and milieu/management factors. Emotional/psychological
consequences of workplace bullying may include increased mental distress, sleep
disturbances, fatigue in women and lack of vigor in men, depression and anxiety,
adjustment disorders, and even work-related suicide. Medical consequences of
workplace bullying may include an increase in health complaints such as neck
pain, musculoskeletal complaints, acute pain, fibromyalgia, and cardiovascular
symptoms. Finally, socioeconomic consequences of workplace bullying may include
absenteeism due to sick days and unemployment. Clinicians in both mental health
and primary care settings need to be alert to the associations between bullying
in the workplace and these potential negative consequences, as patients may not
disclose workplace maltreatment due to embarrassment or fears of retribution.
PMID- 25852979
TI - Path-integral methods for analyzing the effects of fluctuations in stochastic
hybrid neural networks.
AB - We consider applications of path-integral methods to the analysis of a stochastic
hybrid model representing a network of synaptically coupled spiking neuronal
populations. The state of each local population is described in terms of two
stochastic variables, a continuous synaptic variable and a discrete activity
variable. The synaptic variables evolve according to piecewise-deterministic
dynamics describing, at the population level, synapses driven by spiking
activity. The dynamical equations for the synaptic currents are only valid
between jumps in spiking activity, and the latter are described by a jump Markov
process whose transition rates depend on the synaptic variables. We assume a
separation of time scales between fast spiking dynamics with time constant
[Formula: see text] and slower synaptic dynamics with time constant tau. This
naturally introduces a small positive parameter [Formula: see text], which can be
used to develop various asymptotic expansions of the corresponding path-integral
representation of the stochastic dynamics. First, we derive a variational
principle for maximum-likelihood paths of escape from a metastable state (large
deviations in the small noise limit [Formula: see text]). We then show how the
path integral provides an efficient method for obtaining a diffusion
approximation of the hybrid system for small epsilon. The resulting Langevin
equation can be used to analyze the effects of fluctuations within the basin of
attraction of a metastable state, that is, ignoring the effects of large
deviations. We illustrate this by using the Langevin approximation to analyze the
effects of intrinsic noise on pattern formation in a spatially structured hybrid
network. In particular, we show how noise enlarges the parameter regime over
which patterns occur, in an analogous fashion to PDEs. Finally, we carry out a
[Formula: see text]-loop expansion of the path integral, and use this to derive
corrections to voltage-based mean-field equations, analogous to the modified
activity-based equations generated from a neural master equation.
PMID- 25852980
TI - A Mathematical Model of a Midbrain Dopamine Neuron Identifies Two Slow Variables
Likely Responsible for Bursts Evoked by SK Channel Antagonists and Terminated by
Depolarization Block.
AB - Midbrain dopamine neurons exhibit a novel type of bursting that we call "inverted
square wave bursting" when exposed to Ca(2+)-activated small conductance (SK)
K(+) channel blockers in vitro. This type of bursting has three phases:
hyperpolarized silence, spiking, and depolarization block. We find that two slow
variables are required for this type of bursting, and we show that the three
dimensional bifurcation diagram for inverted square wave bursting is a folded
surface with upper (depolarized) and lower (hyperpolarized) branches. The
activation of the L-type Ca(2+) channel largely supports the separation between
these branches. Spiking is initiated at a saddle node on an invariant circle
bifurcation at the folded edge of the lower branch and the trajectory spirals
around the unstable fixed points on the upper branch. Spiking is terminated at a
supercritical Hopf bifurcation, but the trajectory remains on the upper branch
until it hits a saddle node on the upper folded edge and drops to the lower
branch. The two slow variables contribute as follows. A second, slow component of
sodium channel inactivation is largely responsible for the initiation and
termination of spiking. The slow activation of the ether-a-go-go-related (ERG)
K(+) current is largely responsible for termination of the depolarized plateau.
The mechanisms and slow processes identified herein may contribute to bursting as
well as entry into and recovery from the depolarization block to different
degrees in different subpopulations of dopamine neurons in vivo.
PMID- 25852981
TI - A formalism for evaluating analytically the cross-correlation structure of a
firing-rate network model.
AB - We introduce a new formalism for evaluating analytically the cross-correlation
structure of a finite-size firing-rate network with recurrent connections. The
analysis performs a first-order perturbative expansion of neural activity
equations that include three different sources of randomness: the background
noise of the membrane potentials, their initial conditions, and the distribution
of the recurrent synaptic weights. This allows the analytical quantification of
the relationship between anatomical and functional connectivity, i.e. of how the
synaptic connections determine the statistical dependencies at any order among
different neurons. The technique we develop is general, but for simplicity and
clarity we demonstrate its efficacy by applying it to the case of synaptic
connections described by regular graphs. The analytical equations so obtained
reveal previously unknown behaviors of recurrent firing-rate networks, especially
on how correlations are modified by the external input, by the finite size of the
network, by the density of the anatomical connections and by correlation in
sources of randomness. In particular, we show that a strong input can make the
neurons almost independent, suggesting that functional connectivity does not
depend only on the static anatomical connectivity, but also on the external
inputs. Moreover we prove that in general it is not possible to find a mean-field
description a la Sznitman of the network, if the anatomical connections are too
sparse or our three sources of variability are correlated. To conclude, we show a
very counterintuitive phenomenon, which we call stochastic synchronization,
through which neurons become almost perfectly correlated even if the sources of
randomness are independent. Due to its ability to quantify how activity of
individual neurons and the correlation among them depends upon external inputs,
the formalism introduced here can serve as a basis for exploring analytically the
computational capability of population codes expressed by recurrent neural
networks.
PMID- 25852983
TI - Path integral methods for stochastic differential equations.
AB - Stochastic differential equations (SDEs) have multiple applications in
mathematical neuroscience and are notoriously difficult. Here, we give a self
contained pedagogical review of perturbative field theoretic and path integral
methods to calculate moments of the probability density function of SDEs. The
methods can be extended to high dimensional systems such as networks of coupled
neurons and even deterministic systems with quenched disorder.
PMID- 25852982
TI - Modeling focal epileptic activity in the Wilson-cowan model with depolarization
block.
AB - Measurements of neuronal signals during human seizure activity and evoked
epileptic activity in experimental models suggest that, in these pathological
states, the individual nerve cells experience an activity driven depolarization
block, i.e. they saturate. We examined the effect of such a saturation in the
Wilson-Cowan formalism by adapting the nonlinear activation function; we
substituted the commonly applied sigmoid for a Gaussian function. We discuss
experimental recordings during a seizure that support this substitution. Next we
perform a bifurcation analysis on the Wilson-Cowan model with a Gaussian
activation function. The main effect is an additional stable equilibrium with
high excitatory and low inhibitory activity. Analysis of coupled local networks
then shows that such high activity can stay localized or spread. Specifically, in
a spatial continuum we show a wavefront with inhibition leading followed by
excitatory activity. We relate our model simulations to observations of spreading
activity during seizures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version
of this article (doi:10.1186/s13408-015-0019-4) contains supplementary material
1.
PMID- 25852984
TI - Unraveling the kinetic diversity of microbial 3-dehydroquinate dehydratases of
shikimate pathway.
AB - 3-Dehydroquinate dehydratase (DHQase) catalyzes the conversion of 3-dehydroquinic
acid to 3-dehydroshikimic acid of the shikimate pathway. In this study, 3180
prokaryotic genomes were examined and 459 DHQase sequences were retrieved. Based
on sequence analysis and their original hosts, 38 DHQase genes were selected for
chemical synthesis. The selected DHQases were translated into new DNA sequences
according to the genetic codon usage bias by both Escherichia coli and
Corynebacterium glutamicum. The new DNA sequences were customized for synthetic
biological applications by adding Biobrick adapters at both ends and by removal
of any related restriction endonuclease sites. The customized DHQase genes were
successfully expressed in E. coli, and functional DHQases were obtained. Kinetic
parameters of Km, kcat, and Vmax of DHQases were determined with a newly
established high-throughput method for DHQase activity assay. Results showed that
DHQases possessed broad strength of substrate affinities and catalytic
capacities. In addition to the DHQase kinetic diversities, this study generated a
DHQase library with known catalytic constants that could be applied to design
artificial modules of shikimate pathway for metabolic engineering and synthetic
biology.
PMID- 25852985
TI - Fe(III) mineral reduction followed by partial dissolution and reactive oxygen
species generation during 2,4,6-trinitrotoluene transformation by the aerobic
yeast Yarrowia lipolytica.
AB - Understanding the factors that influence pollutant transformation in the presence
of ferric (oxyhydr)oxides is crucial to the efficient application of different
remediation strategies. In this study we determined the effect of goethite,
hematite, magnetite and ferrihydrite on the transformation of 2,4,6
trinitrotoluene (TNT) by Yarrowia lipolytica AN-L15. The presence of ferric
(oxyhydr)oxides led to a small decrease in the rate of TNT removal. In all cases,
a significant release of NO2 (-) from TNT and further NO2 (-) oxidation to NO3 (
) was observed. A fraction of the released NO2 (-) was abiotically decomposed to
NO and NO2, and then NO was likely oxidized abiotically to NO2 by O2. ESR
analysis revealed the generation of superoxide in the culture medium; its further
protonation at low pH resulted in the formation of hydroperoxyl radical.
Presumably, a fraction of NO released during TNT degradation reacted with
superoxide and formed peroxynitrite, which was further rearranged to NO3 (-) at
the acidic pH values observed in this study. A transformation and reduction of
ferric (oxyhydr)oxides followed by partial dissolution (in the range of 7-86% of
the initial Fe(III)) were observed in the presence of cells and TNT. Mossbauer
spectroscopy showed some minor changes for goethite, magnetite and ferrihydrite
samples during their incubation with Y. lipolytica and TNT. This study shows that
i) reactive oxygen and nitrogen species generated during TNT transformation by Y.
lipolytica participate in the abiotic conversion of TNT and ii) the presence of
iron(III) minerals leads to a minor decrease in TNT transformation.
PMID- 25852986
TI - Surface functionalization by covalent immobilization of an innovative carvacrol
derivative to avoid fungal biofilm formation.
AB - Carvacrol, an aromatic terpenic compound, known to be antimicrobial was grafted
onto gold surfaces via two strategies based on newly-synthesized cross-linkers
involving either an ester bond which can be cleaved by microbial esterases, or a
covalent ether link. Surface functionalizations were characterized at each step
by reflection absorption infrared spectroscopy (RAIRS). The two functionalized
gold samples both led to a loss of culturability of the yeast Candida albicans,
higher than 65%, indicating that the activity of the freshly-designed surfaces
was probably due to still covalently immobilized carvacrol. On the contrary, when
a phenyl group replaced the terpenic moiety, the yeast culturability increased by
about 30%, highlighting the specific activity of carvacrol grafted on the
surfaces. Confocal microscopy analyses showed that the mode of action of the
functionalized surfaces with the ester or the ether of carvacrol was, in both
cases, fungicidal and not anti-adhesive. Finally, this study shows that
covalently immobilization of terpenic compounds can be used to design promising
antimicrobial surfaces.
PMID- 25852987
TI - Contribution of soil esterase to biodegradation of aliphatic polyester
agricultural mulch film in cultivated soils.
AB - The relationship between degradation speed of soil-buried biodegradable polyester
film in a farmland and the characteristics of the predominant polyester-degrading
soil microorganisms and enzymes were investigated to determine the BP-degrading
ability of cultivated soils through characterization of the basal microbial
activities and their transition in soils during BP film degradation. Degradation
of poly(butylene succinate-co-adipate) (PBSA) film was evaluated in soil samples
from different cultivated fields in Japan for 4 weeks. Both the degradation speed
of the PBSA film and the esterase activity were found to be correlated with the
ratio of colonies that produced clear zone on fungal minimum medium-agarose plate
with emulsified PBSA to the total number colonies counted. Time-dependent change
in viable counts of the PBSA-degrading fungi and esterase activities were
monitored in soils where buried films showed the most and the least degree of
degradation. During the degradation of PBSA film, the viable counts of the PBSA
degrading fungi and the esterase activities in soils, which adhered to the PBSA
film, increased with time. The soil, where the film was degraded the fastest,
recorded large PBSA-degrading fungal population and showed high esterase activity
compared with the other soil samples throughout the incubation period. Meanwhile,
esterase activity and viable counts of PBSA-degrading fungi were found to be
stable in soils without PBSA film. These results suggest that the higher the
distribution ratio of native PBSA-degrading fungi in the soil, the faster the
film degradation is. This could be due to the rapid accumulation of secreted
esterases in these soils.
PMID- 25852988
TI - Alkyl hydroperoxide reductase enhances the growth of Leuconostoc mesenteroides
lactic acid bacteria at low temperatures.
AB - Lactic acid bacteria (LAB) can cause deterioration of food quality even at low
temperatures. In this study, we investigated the cold-adaptation mechanism of a
novel food spoilage LAB, Leuconostoc mesenteroides NH04 (NH04). L. mesenteroides
was isolated from several spoiled cooked meat products at a high frequency in our
factories. NH04 grew rapidly at low temperatures within the shelf-life period and
resulted in heavy financial losses. NH04 grew more rapidly than related strains
such as Leuconostoc mesenteroides NBRC3832 (NBRC3832) at 10 degrees C. Proteome
analysis of NH04 demonstrated that this strain produces a homolog of alkyl
hydroperoxide reductase--AhpC--the expression of which can be induced at low
temperatures. The expression level of AhpC in NH04 was approximately 6-fold
higher than that in NBRC3832, which was grown under the same conditions. Although
AhpC is known to have an anti-oxidative role in various bacteria by catalyzing
the reduction of alkyl hydroperoxide and hydrogen peroxide, the involvement of
AhpC in cold adaptation of food spoilage bacteria was unclear. We introduced an
expression plasmid containing ahpC into NBRC3832, which grows slower than NH04 at
10 degrees C, and found that expression of AhpC enhanced growth. These results
demonstrated that AhpC, which likely increases anti-oxidative capacity of LAB,
plays an important role in their rapid growth at low temperatures.
PMID- 25852989
TI - Overexpression of PAD1 and FDC1 results in significant cinnamic acid
decarboxylase activity in Saccharomyces cerevisiae.
AB - The S. cerevisiae PAD1 gene had been suggested to code for a cinnamic acid
decarboxylase, converting trans-cinnamic acid to styrene. This was suggested for
the reason that the over-expression of PAD1 resulted in increased tolerance
toward cinnamic acid, up to 0.6 mM. We show that by over-expression of the PAD1
together with the FDC1 the cinnamic acid decarboxylase activity can be increased
significantly. The strain over-expressing PAD1 and FDC1 tolerated cinnamic acid
concentrations up to 10 mM. The cooperation of Pad1p and Fdc1p is surprising
since the PAD1 has a mitochondrial targeting sequence and the FDC1 codes for a
cytosolic protein. The cinnamic acid decarboxylase activity was also seen in the
cell free extract. The activity was 0.019 MUmol per minute and mg of extracted
protein. The overexpression of PAD1 and FDC1 resulted also in increased activity
with the hydroxycinnamic acids ferulic acid, p-coumaric acid and caffeinic acid.
This activity was not seen when FDC1 was overexpressed alone. An efficient
cinnamic acid decarboxylase is valuable for the genetic engineering of yeast
strains producing styrene. Styrene can be produced from endogenously produced L
phenylalanine which is converted by a phenylalanine ammonia lyase to cinnamic
acid and then by a decarboxylase to styrene.
PMID- 25852990
TI - Microbial production of Propionic and Succinic acid from Sorbitol using
Propionibacterium acidipropionici.
AB - Three sequential fermentative batches were carried out with cell recycle in four
simultaneously operating bioreactors maintained at pH 6.5, 30 degrees C, and 100
rpm. P. acidipropionici ATCC 4875 was able to produce propionic and succinic acid
from sorbitol. The concentration of propionic acid decreased slightly from 39.5
+/- 5.2 g L(-1) to 34.4 +/- 1.9 g L(-1), and that of succinic acid increased
significantly from 6.1 +/- 2.1 g L(-1) to 14.8 +/- 0.9 g L(-1) through the
sequential batches. In addition, a small amount of acetic acid was produced that
decreased from 3.3 +/- 0.4 g L(-1) to 2.0 +/- 0.3 g L(-1) through the batches.
The major yield for propionic acid was 0.613 g g(-1) in the first batch and
succinic acid it was 0.212 g g(-1) in the third batch. The minor yield of acetic
acid was 0.029 g g(-1), in the second and third batches.
PMID- 25852991
TI - Engineering of Saccharomyces cerevisiae for the production of poly-3-d
hydroxybutyrate from xylose.
AB - Poly-3-d-hydroxybutyrate (PHB) is a promising biopolymer naturally produced by
several bacterial species. In the present study, the robust baker's yeast
Saccharomyces cerevisiae was engineered to produce PHB from xylose, the main
pentose found in lignocellulosic biomass. The PHB pathway genes from the well
characterized PHB producer Cupriavidus necator were introduced in recombinant S.
cerevisiae strains already capable of pentose utilization by introduction of the
fungal genes for xylose utilization from the yeast Scheffersomyces stipitis. PHB
production from xylose was successfully demonstrated in shake-flasks experiments,
with PHB yield of 1.17 +/- 0.18 mg PHB g(-1) xylose. Under well-controlled fully
aerobic conditions, a titer of 101.7 mg PHB L(-1) was reached within 48 hours,
with a PHB yield of 1.99 +/- 0.15 mg PHB g(-1) xylose, thereby demonstrating the
potential of this host for PHB production from lignocellulose.
PMID- 25852992
TI - Isolation of cellulolytic bacteria from the intestine of Diatraea saccharalis
larvae and evaluation of their capacity to degrade sugarcane biomass.
AB - As a strategy to find efficient lignocellulose degrading enzymes/microorganisms
for sugarcane biomass pretreatment purposes, 118 culturable bacterial strains
were isolated from intestines of sugarcane-fed larvae of the moth Diatraea
saccharalis. All strains were tested for cellulolytic activity using soluble
carboxymethyl cellulose (CMC) degrading assays or by growing bacteria on
sugarcane biomass as sole carbon sources. Out of the 118 strains isolated thirty
eight were found to possess cellulose degrading activity and phylogenetic studies
of the 16S rDNA sequence revealed that all cellulolytic strains belonged to the
phyla gamma-Proteobacteria, Actinobacteria and Firmicutes. Within the three
phyla, species belonging to five different genera were identified (Klebsiella,
Stenotrophomonas, Microbacterium, Bacillus and Enterococcus). Bacterial growth on
sugarcane biomass as well as extracellular endo-glucanase activity induced on
soluble cellulose was found to be highest in species belonging to genera Bacillus
and Klebsiella. Good cellulolytic activity correlated with high extracellular
protein concentrations. In addition, scanning microscopy studies revealed
attachment of cellulolytic strains to different sugarcane substrates. The results
of this study indicate the possibility to find efficient cellulose degrading
enzymes and microorganisms from intestines of insect larvae feeding on sugarcane
and their possible application in industrial processing of sugarcane biomass such
as second generation biofuel production.
PMID- 25852993
TI - Enhanced xylose fermentation and ethanol production by engineered Saccharomyces
cerevisiae strain.
AB - We have recently demonstrated that heterologous expression of a bacterial xylose
isomerase gene (xylA) of Burkholderia cenocepacia enabled a laboratorial
Saccharomyces cerevisiae strain to ferment xylose anaerobically, without xylitol
accumulation. However, the recombinant yeast fermented xylose slowly. In this
study, an evolutionary engineering strategy was applied to improve xylose
fermentation by the xylA-expressing yeast strain, which involved sequential batch
cultivation on xylose. The resulting yeast strain co-fermented glucose and xylose
rapidly and almost simultaneously, exhibiting improved ethanol production and
productivity. It was also observed that when cells were grown in a medium
containing higher glucose concentrations before being transferred to fermentation
medium, higher rates of xylose consumption and ethanol production were obtained,
demonstrating that xylose utilization was not regulated by catabolic repression.
Results obtained by qPCR demonstrate that the efficiency in xylose fermentation
showed by the evolved strain is associated, to the increase in the expression of
genes HXT2 and TAL1, which code for a low-affinity hexose transporter and
transaldolase, respectively. The ethanol productivity obtained after the
introduction of only one genetic modification and the submission to a one-stage
process of evolutionary engineering was equivalent to those of strains submitted
to extensive metabolic and evolutionary engineering, providing solid basis for
future applications of this strategy in industrial strains.
PMID- 25852994
TI - Characterization of the Kluyveromyces marxianus strain DMB1 YGL157w gene product
as a broad specificity NADPH-dependent aldehyde reductase.
AB - The open reading frame YGL157w in the genome of the yeast Kluyveromyces marxianus
strain DMB1 encodes a putative uncharacterized oxidoreductase. However, this
protein shows 46% identity with the Saccharomyces cerevisiae S288c NADPH
dependent methylglyoxal reductase, which exhibits broad substrate specificity for
aldehydes. In the present study, the YGL157w gene product (KmGRE2) was purified
to homogeneity from overexpressing Escherichia coli cells and found to be a
monomer. The enzyme was strictly specific for NADPH and was active with a wide
variety of substrates, including aliphatic (branched-chain and linear) and
aromatic aldehydes. The optimal pH for methylglyoxal reduction was 5.5. With
methylglyoxal as a substrate, the optimal temperature for enzyme activity at pH
5.5 was 45 degrees C. The enzyme retained more than 70% of its activity after
incubation for 30 min at temperatures below 35 degrees C or at pHs between 5.5
and 9.0. In addition, the KmGRE2-overexpressing E. coli showed improved growth
when cultivated in cedar hydrolysate, as compared to cells not expressing the
enzyme. Taken together, these results indicate that KmGRE2 is potentially useful
as an inhibit decomposer in E. coli cells.
PMID- 25852995
TI - Strain and process development for poly(3HB-co-3HP) fermentation by engineered
Shimwellia blattae from glycerol.
AB - Poly(3-hydroxybytyrate-co-3-hydroxypropionate), poly(3HB-co-3HP), is a possible
alternative to synthetic polymers such as polypropylene, polystyrene and
polyethylene due to its low crystallinity and fragility. We already reported that
recombinant strains of Shimwellia blattae expressing 1,3-propanediol
dehydrogenase DhaT as well as aldehyde dehydrogenase AldD of Pseudomonas putida
KT2442, propionate-CoA transferase Pct of Clostridium propionicum X2 and PHA
synthase PhaC1 of Ralstonia eutropha H16 are able to accumulate up to 14.5%
(wtPHA/wtCDW) of poly(3-hydroxypropionate), poly(3HP), homopolymer from glycerol
as a sole carbon source (Appl Microbiol Biotechnol 98:7409-7422, 2014a). However,
the cell density was rather low. In this study, we optimized the medium aiming at
a more efficient PHA synthesis, and we engineered a S. blattae strain
accumulating poly(3HB-co-3HP) with varying contents of the constituent 3
hydroxypropionate (3HP) depending on the cultivation conditions. Consequently,
7.12, 0.77 and 0.32 gPHA/L of poly(3HB-co-3HP) containing 2.1, 8.3 and 18.1 mol%
3HP under anaerobic/aerobic (the first 24 hours under anaerobic condition,
thereafter, aerobic condition), low aeration/agitation (the minimum stirring rate
required in medium mixing and small amount of aeration) and anaerobic conditions
(the minimum stirring rate required in medium mixing without aeration),
respectively, were synthesized from glycerol by the genetically modified S.
blattae ATCC33430 strains in optimized culture medium.
PMID- 25852996
TI - Induction, expression and characterisation of laccase genes from the marine
derived fungal strains Nigrospora sp. CBMAI 1328 and Arthopyrenia sp. CBMAI 1330.
AB - The capability of the fungi Nigrospora sp. CBMAI 1328 and Arthopyrenia sp. CBMAI
1330 isolated from marine sponge to synthesise laccases (Lcc) in the presence of
the inducer copper (1-10 MUM) was assessed. In a liquid culture medium
supplemented with 5 MUM of copper sulphate after 5 days of incubation, Nigrospora
sp. presented the highest Lcc activity (25.2 U.L(-1)). The effect of copper on
Lcc gene expression was evaluated by reverse transcriptase polymerase chain
reaction. Nigrospora sp. showed the highest gene expression of Lcc under the same
conditions of Lcc synthesis. The highest Lcc expression by the Arthopyrenia sp.
was detected at 96 h of incubation in absence of copper. Molecular approaches
allowed the detection of Lcc isozymes and suggest the presence of at least two
undescribed putative genes. Additionally, Lcc sequences from the both fungal
strains clustered with other Lcc sequences from other fungi that inhabit marine
environments.
PMID- 25852997
TI - Recombinant glucagon: a differential biological activity.
AB - In Brazil, there is a growing demand for specialised pharmaceuticals, and the
high cost of their importation results in increasing costs, reaching US$ 1.34
billion in 2012 and US$ 1.61 billion in 2013. Worldwide expenses related to drugs
could reach US$ 1.3 trillion in 2018, especially due to new treatments for
hepatitis C and cancer. Specialised or high-cost pharmaceutical drugs used for
the treatment of viral hepatitis, multiple sclerosis, HIV and diabetes are
distributed free of charge by the Brazilian government. The glucagon peptide was
included in this group of high-cost biopharmaceuticals in 2008. Although its main
application is the treatment of hypoglycaemia in diabetic patients, it can also
be used with patients in an alcoholic coma, for those patients with biliary tract
pain, and as a bronchodilator. Therefore, in order to reduce biopharmaceutical
production costs, the Brazilian government passed laws focusing on the
development and increase of a National Pharmaceutical Industrial Centre,
including the demand for the national production of glucagon. For that reason and
given the importance and high cost of recombinant glucagon, the purpose of this
study was to develop methods to improve production, purification and performance
of the biological activity of recombinant glucagon. Glucagon was recombined into
a plasmid vector containing a Glutathione S-transferase tag, and the peptide was
expressed in a heterologous Escherichia coli system. After purification
procedures and molecular analyses, the biological activity of this recombinant
glucagon was examined using in vivo assays and showed a highly significant (p <
0.00001) and prolonged effect on glucose levels when compared with the standard
glucagon. The experimental procedure described here facilitates the high level
production of recombinant glucagon with an extended biological activity.
PMID- 25852998
TI - Foam-free production of Surfactin via anaerobic fermentation of Bacillus subtilis
DSM 10(T).
AB - Surfactin is one of the most popular biosurfactants due to its numerous potential
applications. The usually aerobic production via fermentation of Bacillus
subtilis is accompanied by vigorous foaming which leads to complex constructions
and great expense. Therefore it is reasonable to search for alternative foam-free
production processes. The current study introduces a novel approach to produce
Surfactin in a foam-free process applying a strictly anaerobic bioreactor
cultivation. The process was performed several times with different glucose
concentrations in mineral salt medium. The fermentations were analyzed regarding
specific (qSurfactin, vol. qSurfactin) and overall product yields (YP/X, YP/S) as
well as substrate utilization (YX/S). Fermentations in which 2.5 g/L glucose were
employed proofed to be the most effective, reaching product yields of YP/X =
0.278 g/g. Most interesting, the product yields exceeded classical aerobic
fermentations, in which foam fractionation was applied. Additionally, values for
specific production rate qSurfactin (0.005 g/(g?h)) and product yield per
consumed substrate (YP/S = 0.033 g/g) surpass results of comparable foam-free
processes. The current study introduces an alternative to produce a biosurfactant
that overcomes the challenges of severe foaming and need for additional
constructions.
PMID- 25852999
TI - The social and economic determinants of suicide in Canadian provinces.
AB - BACKGROUND: In this paper we investigate the causal relationship between suicide
and a variety of socioeconomic variables. We use a panel data set of Canadian
provinces, 2000 - 2008, and a set of recent panel econometric techniques in order
to account for a variety of statistical specification issues. RESULTS: We find
that the social and economic determinants of suicide in Canadian provinces vary
across total, male, and female counts (natural logarithms) and rates. We also
find that the results vary depending on the econometric method employed. As such,
separate analyses for males and females is necessary for a better understanding
of the factors that impact suicide (consistent with previous research) and that
the choice of statistical method impacts the results. Lastly, it is important to
note the particular provinces are driving the results for particular
socioeconomic variables. CONCLUSIONS: Such a result, if generalizable, has
significant implications for suicide prevention policy.
PMID- 25853000
TI - Socio-economic determinants of life expectancy in Nigeria (1980 - 2011).
AB - Attainment of 70 years life expectancy by 2020 is one of the millennium
development goals in Nigeria. This study examined the socio-economic determinants
of life expectancy in Nigeria using data from 1980-2011. Judging from the
endogeneity feature of the variables, A VAR and VECM frameworks were employed.
Socio-economic features were proxy by secondary school enrolment, government
expenditure on health, per capita income, unemployment rate and the Naira foreign
exchange rate. It was found that, the conventional socio-economic variables such
as per capita income, education and government expenditure on health considered
to be highly effective in determining life expectancy of developing countries are
not significant in the case of Nigeria. The study however suggests that, life
expectancy in Nigeria could be improved if attention is given to quality of
government health expenditure, unemployment and measures to halt the depreciation
of the Nigerian Naira against major foreign currency.
PMID- 25853001
TI - Is healthcare a 'Necessity' or 'Luxury'? an empirical evidence from public and
private sector analyses of South-East Asian countries?
AB - South-East Asian Regional (SEAR) countries range from low- to middle-income
countries and have considerable differences in mix of public and private sector
expenditure on health. This study intends to estimate the income-elasticities of
healthcare expenditure in public and private sectors separately for investigating
whether healthcare is a 'necessity' or 'luxury' for citizens of these countries.
Panel data from 9 SEAR countries over 16 years (1995-2010) were employed. Fixed-
and random-effect models were fitted to estimate income-elasticity of public,
private and total healthcare expenditure. Results showed that one percent point
increase in GDP per capita increased private expenditure on healthcare by 1.128%,
while public expenditure increased by only 0.412%. Inclusion of three-year lagged
variables of GDP per capita in the models did not have remarkable influence on
the findings. The citizens of SEAR countries consider healthcare as a necessity
while provided through public sector and a luxury when delivered by private
sector. By increasing the public provisions of healthcare, more redistribution of
healthcare resources can be ensured, which can accelerate the journey of SEAR
countries towards universal health coverage.
PMID- 25853002
TI - A reconstruction of a medical history from administrative data: with an
application to the cost of skin cancer.
AB - The medical record is a repository of clinical data, which can greatly enhance
the quality of health and healthcare analysis. Administrative data are collected
for the purpose of billing and reimbursement, and are valued by health
researchers because the data are routinely audited to maintain accurate financial
records. However, the quantity of incorporated clinical data can be variable. In
this paper we reconstruct the medical record from health service invoices to
estimate the cost of treating keratinocytic cancer (KC). The data from an
epidemiological survey were linked to an administrative data set supplied by the
national health insurer. A matched sampling technique with multivariable analysis
was used to estimate cost. A KC treatment was identified with 42 service codes
which explicitly nominated treatment of a KC. Algorithms identifying comorbities
potentially correlated with KC were constructed from the service codes. The
annual cost of a KC treatment was estimated to be AU$667 per individual. The
average cost of explicit KC treatments was AU$231, while the cost of generic
procedures used to treat KC was AU$436. Our ability to accurately control for the
medical history enabled our analysis to quantify and describe the constituent
costs of KC treatment.
PMID- 25853003
TI - The Nigeria wealth distribution and health seeking behaviour: evidence from the
2012 national HIV/AIDS and reproductive health survey.
AB - BACKGROUND: Recently, Nigeria emerged as the largest economy in Africa and the
26th in the world. However, a pertinent question is how this new economic status
has impacted on the wealth and health of her citizens. There is a dearth of
empirical study on the wealth distribution in Nigeria which could be important in
explaining the general disparities in their health seeking behavior. An adequate
knowledge of Nigeria wealth distribution will no doubt inform policy makers in
their decision making to improve the quality of life of Nigerians. METHOD: This
study is a retrospective analysis of the assets of household in Nigeria collected
during the 2012 National HIV/AIDS and Reproductive Health Survey (NARHS Plus 2).
We used the principal component analysis methods to construct wealth quintiles
across households in Nigeria. At 5% significance level, we used ANOVA to
determine differences in some health outcomes across the WQs and chi-square test
to assess association between WQs and some reproductive health seeking
behaviours. RESULT: The wealth quintiles were found to be internally valid and
coherent. However, there is a wide gap in the reproductive health seeking
behavior of household members across the wealth quintiles with members of
households in lower quintiles having lesser likelihood (33.0%) to receive
antenatal care than among those in the highest quintiles (91.9%). While only 3%
were currently using modern contraceptives in the lowest wealth quintile, it was
17.4% among the highest wealth quintile (p < 0.05). CONCLUSION: The wealth
quintiles showed a great disparity in the standard of living of Nigerian
households across geo-political zones, states and rural-urban locations which had
greatly influenced household health seeking behavior.
PMID- 25853004
TI - Binge drinking and alcohol prices: a systematic review of age-related results
from econometric studies, natural experiments and field studies.
AB - BACKGROUND: Heavy episodic ("binge") drinking of alcohol has serious public
health implications, especially for youth and young adults. Previous summaries
and surveys have failed to address in a comprehensive manner the effects of
alcohol prices on binge drinking by gender or age group. METHODS: A qualitative
systematic review is performed for effects of alcohol prices (or tax surrogates)
on binge drinking for three age groups: youth, young adults, and adults. Outcomes
examined include binge participation, intensity and frequency. Criteria for data
collection and potential sources of bias are discussed, including adequacy of
price data. Price-binge relationships are judged using a 95% confidence interval
(p <= 0.05) for statistical significance. RESULTS: Fifty-six relevant econometric
studies were found, with studies and results distributed equally among three age
groups. Also found were five natural experiments for tax reductions and six field
studies. Null results or mixed results are found in more than half of the
studies. The body of evidence indicates that binge drinkers are not highly
responsive to increased prices. Non-responsiveness holds generally for younger
and older drinkers and for male and female binge drinkers alike. A limitation of
the current literature is that results are only available for higher-income
countries. CONCLUSIONS: Increased alcohol taxes or prices are unlikely to be
effective as a means to reduce binge drinking, regardless of gender or age group.
PMID- 25853005
TI - The Role of decision-analytic modelling in German health technology assessments.
AB - BACKGROUND: Decision-analytic modelling (DAM) has become a widespread method in
health technology assessments (HTA), but the extent to which modelling is used
differs among international HTA institutions. In Germany, the use of DAM is
optional within HTAs of the German Institute of Medical Documentation and
Information (DIMDI). Our study examines the use of DAM in DIMDI HTA reports and
its effect on the quality of information provided for health policies. METHODS: A
review of all DIMDI HTA reports (from 1998 to September 2012) incorporating an
economic assessment was performed. All included reports were divided into two
groups: HTAs with DAM and HTAs without DAM. In both groups, reports were
categorized according to the quality of information provided for healthcare
decision making. RESULTS: Of the sample of 107 DIMDI HTA reports, 17 (15.9%) used
DAM for economic assessment. In the group without DAM, conclusions were limited
by the quality of economic information in 51.1% of the reports, whereas we did
not find limited conclusions in the group with DAM. Furthermore, 24 reports
without DAM (26.7%) stated that using DAM would likely improve the quality of
information of the economic assessment. CONCLUSION: The use of DAM techniques can
improve the quality of HTAs in Germany. When, after a systematic review of
existing literature within a HTA, it is clear that DAM is likely to positively
affect the quality of the economic assessment DAM should be used.
PMID- 25853006
TI - Effect of timely initiation of breastfeeding on child health in Ghana.
AB - BACKGROUND: Early initiation of breastfeeding and exclusive breastfeeding
practices have been argued to be one of the important ways of ensuring child
health. Unfortunately, owing to modernization, most nursing mothers fail to
adhere to such practices. This is believed to be a factor contributory to poor
child health in Ghana. Thus, this study investigated the effect of timely
initiation of breastfeeding on child health in Ghana. METHODS: Cross sectional
data using secondary data based on the positivism approach to research was
employed. The Ordinary least squares and the Instrumental variables approach were
used in estimating the effect of breastfeeding and other socio demographic
indicators on the health of the child. Data for the study was sourced from the
2008 round of the Ghana Demographic and Health Survey. RESULTS: The results
indicate that timely initiation of breastfeeding, both immediately and hours
after birth are important factors that influence the child's health.
Additionally, factors such as the wealth of the household, mother's education,
age and size of the child at birth and age of the mother are important factors
that also influence the health of the child in Ghana. CONCLUSION: The findings
imply that efforts should be made on encouraging appropriate breastfeeding
practices among nursing mothers to ensure proper child development and growth in
Ghana.
PMID- 25853007
TI - Transcriptional response in normal mouse tissues after i.v. (211)At
administration - response related to absorbed dose, dose rate, and time.
AB - BACKGROUND: In cancer radiotherapy, knowledge of normal tissue responses and
toxicity risks is essential in order to deliver the highest possible absorbed
dose to the tumor while maintaining normal tissue exposure at non-critical
levels. However, few studies have investigated normal tissue responses in vivo
after (211)At administration. In order to identify molecular biomarkers of
ionizing radiation exposure, we investigated genome-wide transcriptional
responses to (very) low mean absorbed doses from (211)At in normal mouse tissues.
METHODS: Female BALB/c nude mice were intravenously injected with 1.7 kBq (211)At
and killed after 1 h, 6 h, or 7 days or injected with 105 or 7.5 kBq and killed
after 1 and 6 h, respectively. Controls were mock-treated. Total RNA was
extracted from tissue samples of kidney cortex and medulla, liver, lungs, and
spleen and subjected to microarray analysis. Enriched biological processes were
categorized after cellular function based on Gene Ontology terms. RESULTS:
Responses were tissue-specific with regard to the number of significantly
regulated transcripts and associated cellular function. Dose rate effects on
transcript regulation were observed with both direct and inverse trends. In
several tissues, Angptl4, Per1 and Per2, and Tsc22d3 showed consistent transcript
regulation at all exposure conditions. CONCLUSIONS: This study demonstrated
tissue-specific transcriptional responses and distinct dose rate effects after
(211)At administration. Transcript regulation of individual genes, as well as
cellular responses inferred from enriched transcript data, may serve as
biomarkers in vivo. These findings expand the knowledge base on normal tissue
responses and may help to evaluate and limit side effects of radionuclide
therapy.
PMID- 25853008
TI - Molecular imaging of angiogenesis after myocardial infarction by (111)In-DTPA
cNGR and (99m)Tc-sestamibi dual-isotope myocardial SPECT.
AB - BACKGROUND: CD13 is selectively upregulated in angiogenic active endothelium and
can serve as a target for molecular imaging tracers to non-invasively visualise
angiogenesis in vivo. Non-invasive determination of CD13 expression can
potentially be used to monitor treatment response to pro-angiogenic drugs in
ischemic heart disease. CD13 binds peptides and proteins through binding to
tripeptide asparagine-glycine-arginine (NGR) amino acid residues. Previous
studies using in vivo fluorescence microscopy and magnetic resonance imaging
indicated that cNGR tripeptide-based tracers specifically bind to CD13 in
angiogenic vasculature at the border zone of the infarcted myocardium. In this
study, the CD13-binding characteristics of an (111)In-labelled cyclic NGR peptide
(cNGR) were determined. To increase sensitivity, we visualised (111)In-DTPA-cNGR
in combination with (99m)Tc-sestamibi using dual-isotope SPECT to localise CD13
expression in perfusion-deficient regions. METHODS: Myocardial infarction (MI)
was induced in Swiss mice by ligation of the left anterior descending coronary
artery (LAD). (111)In-DTPA-cNGR and (99m)Tc-sestamibi dual-isotope SPECT imaging
was performed 7 days post-ligation in MI mice and in control mice. In addition,
ex vivo SPECT imaging on excised hearts was performed, and biodistribution of
(111)In-DTPA-cNGR was determined using gamma counting. Binding specificity of
(111)In-DTPA-cNGR to angiogenic active endothelium was determined using the
Matrigel model. RESULTS: Labelling yield of (111)In-DTPA-cNGR was 95% to 98% and
did not require further purification. In vivo, (111)In-DTPA-cNGR imaging showed a
rapid clearance from non-infarcted tissue and a urinary excretion of 82% of the
injected dose (I.D.) 2 h after intravenous injection in the MI mice. Specific
binding of (111)In-DTPA-cNGR was confirmed in the Matrigel model and, moreover,
binding was demonstrated in the infarcted myocardium and infarct border zone.
CONCLUSIONS: Our newly designed and developed angiogenesis imaging probe (111)In
DTPA-cNGR allows simultaneous imaging of CD13 expression and perfusion in the
infarcted myocardium and the infarct border zone by dual-isotope micro-SPECT
imaging.
PMID- 25853009
TI - Role of CD8-positive cells in radioimmunotherapy utilizing (177)Lu-mAbs in an
immunocompetent rat colon carcinoma model.
AB - BACKGROUND: CD8-positive cells might play a crucial role in the therapeutic
response to radiation, which has however not been investigated in
radioimmunotherapy (RIT). The aim of this study was to evaluate whether cytotoxic
T cells affect the response of established tumors and, above all, if they delay
or prevent the development of distant metastases after RIT, using an
immunocompetent syngeneic rat colon carcinoma model. METHODS: The cytotoxic T
cells were depleted in 15 rats by anti-CD8 before the injection of the
radioimmunoconjugate (400 MBq/kg body weight (177)Lu-BR96, which binds to the
tumor-associated antigen Lewis Y). Fifteen other rats were treated with RIT only.
Both groups were followed for 99 days. Blood samples were collected at least once
weekly, and tumors were monitored twice weekly. RESULTS: Twenty-nine of the 30
animals exhibited local complete response. The non-responder was treated with
anti-CD8 and RIT but succumbed later due to metastases. Five animals in the group
given anti-CD8 + RIT were sacrificed due to metastatic disease, and 4 additional
animals were found to have metastases at autopsy. In the group given RIT, 4
animals developed metastatic disease, but no metastases were found in the
remaining 11 animals at autopsy. Thus, at the end of the study, 6 animals in the
anti-CD8 + RIT group were free from metastases, while 11 were free from
metastases in the group receiving RIT. CD3(+)CD4(-)CD8(+) lymphocytes were
consistently depleted by the anti-CD8 treatment. The myelosuppression was
otherwise similar in the two groups. The initial depletion of CD8-positive cells
in our syngeneic rat colon carcinoma model resulted in a higher frequency of
animals developing metastases. CONCLUSIONS: Depletion of CD8-positive cells
during RIT in an immunocompetent rat tumor model might influence the number of
animals developing metastases, indicating that the immune system may be important
in the long-term outcome of RIT.
PMID- 25853010
TI - Identifying erlotinib-sensitive non-small cell lung carcinoma tumors in mice
using [(11)C]erlotinib PET.
AB - BACKGROUND: Non-small cell lung carcinoma (NSCLC) represents approximately 80% of
lung cancer cases, and over 60% of these tumors express the epidermal growth
factor receptor (EGFR). Activating mutations in the tyrosine kinase (TK) domain
of the EGFR are detected in 10% to 30% of NSCLC patients, and evidence of their
presence is a prerequisite for initiation of first-line therapy with selective TK
inhibitors (TKIs), such as gefitinib and erlotinib. To date, the selection of
candidate patients for first-line treatment with EGFR TKIs requires an invasive
tumor biopsy to affirm the mutational status of the receptor. This study was
designed to evaluate whether positron emission tomography (PET) of NSCLC tumor
bearing mice using [(11)C]erlotinib could distinguish erlotinib-sensitive from
erlotinib-insensitive or erlotinib-resistant tumors. METHODS: Four human NSCLC
cell lines were employed, expressing either of the following forms of the EGFR:
(i) the wild-type receptor (QG56 cells), (ii) a mutant with an exon 19 in-frame
deletion (HCC827 cells), (iii) a mutant with the exon 21 L858R point mutation
(NCI-H3255 cells), and (iv) a double mutant harboring the L858R and T790M
mutations (NCI-H1975 cells). Sensitivity of each cell line to the anti
proliferative effect of erlotinib was determined in vitro. In vivo PET imaging
studies following i.v. injection of [(11)C]erlotinib were carried out in nude
mice bearing subcutaneous (s.c.) xenografts of the four cell lines. RESULTS:
Cells harboring activating mutations in the EGFR TK domain (HCC827 and NCI-H3255)
were approximately 1,000- and 100-fold more sensitive to erlotinib treatment in
vitro, respectively, compared to the other two cell lines. [(11)C]Erlotinib PET
scans could differentiate erlotinib-sensitive tumors from insensitive (QG56) or
resistant (NCI-H1975) tumors already at 12 min after injection. Nonetheless, the
uptake in HCC827 tumors was significantly higher than that in NCI-H3255, possibly
reflecting differences in ATP and erlotinib affinities between the EGFR mutants.
CONCLUSIONS: [(11)C]Erlotinib imaging in mice differentiates erlotinib-sensitive
NSCLC tumors from erlotinib-insensitive or erlotinib-resistant ones.
PMID- 25853011
TI - The ultimate radiochemical nightmare: upon radio-iodination of Botulinum
neurotoxin A, the introduced iodine atom itself seems to be fatal for the
bioactivity of this macromolecule.
AB - BACKGROUND: Botulinum neurotoxin A (BoNT-A) is a highly neurotoxic drug and
frequently used in patients. Knowledge on the optimal way of administration of
BoNT-A and its subsequent distribution is still rather limited. An accurate
method for monitoring these processes might be the use of radiolabelled BoNT-A.
In this paper, we report our feasibility study on labelling BoNT-A with high-dose
iodine-125 ((125)I) via IODOGEN-coated BoNT-A method. METHODS: Using cetuximab as
model substrate for BoNT-A, a miniaturization of the IODOGEN-coated mAb method
was developed with special attention to the minimum required amount of the
oxidant IODOGEN, while the amount of substrate, reaction volume and reaction time
were downsized. Labelling efficiency and radiochemical purity were determined by
TLC, integrity by SDS-PAGE and HPLC and immunoreactivity by cell-binding assay.
BoNT-A (50 MUg) was labelled with (125)I by coating with 2.5 MUg IODOGEN, in a
total reaction volume of 250 MUL and a reaction time of 90 s. (125)I-BoNT-A was
purified by size exclusion chromatography (PD10 column) using ascorbic acid
solution (5 mg/ml, pH = 5) as eluent. Quality analysis of (125)I-BoNT-A was
performed by an in vitro bladder strip model, an electrochemiluminescence assay
and an Endopep assay. RESULTS: Cetuximab (50 MUg) labelling with (125)I (15 to
150 MBq) resulted in a labelling efficiency of 70% to 80%, a radiochemical purity
of >99%, an immunoreactivity of >95% and a retained integrity on SDS; HPLC
analysis revealed partly affected integrity when 110 to 150 MBq (125)I was used,
i.e. when the averaged I/mAb molar ratio exceeded 3. Addition of HEPES (20 mM)
and lactose (1.25%) (lyophilized BoNT-A contains HEPES and lactose) decreased the
labelling efficiency to 44% to 54%. BoNT-A (50 MUg) labelling with (125)I (97.2
to 98.3 MBq) resulted in labelling efficiency of 51% to 52% with a radiochemical
purity >98.5%, a specific activity of 150.5 to 152.9 MBq/nmol and an I/BoNT-A
molar ratio of 1.86 to 1.90. The in vitro bladder strip model showed no
bioactivity of (125)I-BoNT-A when compared to unlabelled BoNT-A. The
electrochemiluminescence and Endopep assay demonstrated around 10% and 15%
bioactivity of (125)I-BoNT-A compared to unlabelled BoNT-A, respectively. The
remaining bioactivity correlates within the Poisson distribution with the amount
of BoNT-A molecules that does not bear an iodine atom. CONCLUSIONS: BoNT-A was
successfully radio-iodinated with an activity high enough to enable in vivo
measurement of nanograms of BoNT-A, which could be used in studying optimization
of administration techniques of BoNT-A. The bioactivity of a BoNT-A molecule is,
however, lost upon the introduction of an iodine atom into the tyrosine moiety of
this sensitive molecule.
PMID- 25853012
TI - An assessment of the characteristics and quality of diagnostic accuracy studies
for positron emission tomography conducted in Japan: a systematic review.
AB - BACKGROUND: Systematic evaluations of the diagnostic accuracy of positron
emission tomography (PET) imaging have been widely conducted in many countries.
Although Japan's total number of PET units is the second highest in the world,
very limited effort has been made to systematically assess the methodological
quality of PET studies in Japan. We performed a systematic review to assess the
characteristics and quality of PET diagnostic accuracy studies conducted in Japan
and to analyze the factors related to their quality. METHODS: All PET studies
conducted in Japan were identified using MEDLINE and the Japan Medical Abstract
Society Database. The characteristics of the Japanese studies were examined and
their methodological quality evaluated by the standardized quality assessment of
diagnostic accuracy studies (QUADAS) tool. We compared the quality of studies
indexed in MEDLINE with non-indexed studies, followed by a comparison of the
studies' conclusions with those of international health technology assessment
(HTA) reports. RESULTS: A total of 138 studies were identified. Half of them were
not indexed in MEDLINE. The mean quality score of the Japanese studies was 6.7
and the proportion of high-quality studies (with a quality score higher than 8)
was 32.6%. A significant difference was observed in several quality items between
MEDLINE-indexed and non-indexed studies, although there was no difference in
total quality score. Three variables (i.e., target diseases, publication year,
and study type) were identified as factors related to the quality of the studies.
Conclusions of Japanese studies relating to several target diseases were
relatively consistent with international assessments. CONCLUSIONS: Although a
considerable number of diagnostic accuracy studies of PET have been conducted in
Japan, a substantial proportion of high-quality studies were not indexed in
international databases. High-quality Japanese studies, therefore, should be
searched using Japanese databases and assessed by systematic reviews and HTA
conducted internationally.
PMID- 25853013
TI - Comparison of 4'-[methyl-(11)C]thiothymidine ((11)C-4DST) and 3'-deoxy-3'
[(18)F]fluorothymidine ((18)F-FLT) PET/CT in human brain glioma imaging.
AB - BACKGROUND: 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been used to
evaluate tumor malignancy and cell proliferation in human brain gliomas. However,
(18)F-FLT has several limitations in clinical use. Recently, (11)C-labeled
thymidine analogue, 4'-[methyl-(11)C]thiothymidine ((11)C-4DST), became available
as an in vivo cell proliferation positron emission tomography (PET) tracer. The
present study was conducted to evaluate the usefulness of (11)C-4DST PET in the
diagnosis of human brain gliomas by comparing with the images of (18)F-FLT PET.
METHODS: Twenty patients with primary and recurrent brain gliomas underwent (18)F
FLT and (11)C-4DST PET scans. The uptake values in the tumors were evaluated
using the maximum standardized uptake value (SUVmax), the tumor-to-normal tissue
uptake (T/N) ratio, and the tumor-to-blood uptake (T/B) ratio. These values were
compared among different glioma grades. Correlation between the Ki-67 labeling
index and the uptake values of (11)C-4DST and (18)F-FLT in the tumor was
evaluated using linear regression analysis. The relationship between the
individual (18)F-FLT and (11)C-4DST uptake values in the tumors was also
examined. RESULTS: (11)C-4DST uptake was significantly higher than that of (18)F
FLT in the normal brain. The uptake values of (11)C-4DST in the tumor were
similar to those of (18)F-FLT resulting in better visualization with (18)F-FLT.
No significant differences in the uptake values of (18)F-FLT and (11)C-4DST were
noted among different glioma grades. Linear regression analysis showed a
significant correlation between the Ki-67 labeling index and the T/N ratio of
(11)C-4DST (r = 0.50, P < 0.05) and (18)F-FLT (r = 0.50, P < 0.05). Significant
correlations were also found between the Ki-67 labeling index and the T/B ratio
of (11)C-4DST (r = 0.52, P < 0.05) and (18)F-FLT (r = 0.55, P < 0.05). A highly
significant correlation was observed between the individual T/N ratio of (11)C
4DST and (18)F-FLT in the tumor (r = 0.79, P = 0.0001). CONCLUSIONS: The present
study demonstrates that (11)C-4DST is useful for the imaging of human brain
gliomas with PET. A relatively higher background uptake of (11)C-4DST in the
normal brain compared to (18)F-FLT limits the detection of low-tracer-uptake
tumors. Moreover, no superiority was found in (11)C-4DST over (18)F-FLT in the
evaluation of cell proliferation.
PMID- 25853014
TI - (64)Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in
HER2-positive breast cancer patients.
AB - BACKGROUND: The purpose of this study was to determine whether brain metastases
from HER2-positive breast cancer could be detected noninvasively using positron
emission tomography (PET) with (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10
tetraacetic acid (DOTA)-trastuzumab. METHODS: PET was performed on five patients
with brain metastases from HER2-positive breast cancer, at 24 or 48 h after the
injection of approximately 130 MBq of the probe (64)Cu-DOTA-trastuzumab.
Radioactivity in metastatic brain tumors was evaluated based on PET images in
five patients. Autoradiography, immunohistochemistry (IHC), and liquid
chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed in one
surgical case to confirm HER2 specificity of (64)Cu-DOTA-trastuzumab. RESULTS:
Metastatic brain lesions could be visualized by (64)Cu-DOTA-trastuzumab PET in
all of five cases, which might indicated that trastuzumab passes through the
blood-brain barrier (BBB). The HER2 specificity of (64)Cu-DOTA-trastuzumab was
demonstrated in one patient by autoradiography, immunohistochemistry, and LC
MS/MS. CONCLUSIONS: Cu-DOTA-trastuzumab PET could be a potential noninvasive
procedure for serial identification of metastatic brain lesions in patients with
HER2-positive breast cancer. TRIAL REGISTRATION: UMIN000004170.
PMID- 25853015
TI - SPECT imaging of glioma with radioiodinated CLINDE: evidence from a mouse GL26
glioma model.
AB - BACKGROUND: Recent research has demonstrated the potential of 18-kDa translocator
protein (TSPO) to serve as a target for nuclear imaging of gliomas. The aim of
this study was to evaluate SPECT imaging of GL26 mouse glioma using
radioiodinated CLINDE, a TSPO-specific tracer. METHODS: GL26 cells, previously
transfected with an enhanced green fluorescent protein (EGFP)-expressing
lentivirus, were stereotactically implanted in the striatum of C57/Bl6 mice. At 4
weeks post-injection, dynamic SPECT scans with [(123)I]CLINDE were performed. A
displacement study assessed specificity of tracer binding. SPECT images were
compared to results of autoradiography, fluorescence microscopy, in situ nucleic
acid hybridization, histology, and immunohistochemistry. Western blotting was
performed to verify TSPO production by the tumor. RESULTS: Specific uptake of
tracer by the tumor is observed with a high signal-to-noise ratio. Tracer uptake
by the tumor is indeed 3.26 +/- 0.32 times higher than that of the contralateral
striatum, and 78% of the activity is displaceable by unlabeled CLINDE. Finally,
TSPO is abundantly expressed by the GL26 cells. CONCLUSIONS: The present study
demonstrates the feasibility of [(123)I]CLINDE SPECT in translational studies and
underlines its potential for clinical glioma SPECT imaging.
PMID- 25853016
TI - Heterogeneity of intratumoral (111)In-ibritumomab tiuxetan and (18)F-FDG
distribution in association with therapeutic response in radioimmunotherapy for B
cell non-Hodgkin's lymphoma.
AB - BACKGROUND: The purpose of this study was to quantitatively evaluate the tumor
accumulation and heterogeneity of (111)In-ibritumomab tiuxetan (Zevalin(r)) and
tumor accumulation of (18)F-fluoro-deoxyglucose (FDG) and compare them to the
tumor response in B-cell non-Hodgkin's lymphoma patients receiving (90)Y
ibritumomab tiuxetan (Zevalin(r)) therapy. METHODS: Sixteen patients with
histologically confirmed non-Hodgkin's B-cell lymphoma who underwent (90)Y
ibritumomab tiuxetan therapy along with (111)In-ibritumomab tiuxetan single
photon emission computerized tomography (SPECT)/CT and FDG positron emission
tomography (PET)/CT were enrolled in this retrospective study. On pretherapeutic
FDG PET/CT images, the maximum standardized uptake value (SUVmax) was measured.
On SPECT/CT images, a percentage of the injected dose per gram (%ID/g) and SUVmax
of (111)In-ibritumomab tiuxetan were measured at 48 h after its administration.
The skewness and kurtosis of the voxel distribution were calculated to evaluate
the intratumoral heterogeneity of tumor accumulation. As another intratumoral
heterogeneity index, cumulative SUV-volume histograms describing the percentage
of the total tumor volume above the percentage thresholds of pretherapeutic FDG
and (111)In-ibritumomab tiuxetan SUVmax (area under the curve of the cumulative
SUV histograms (AUC-CSH)) were calculated. All lesions (n = 42) were classified
into responders and non-responders lesion-by-lesion on pre- and post-therapeutic
CT images. RESULTS: A positive correlation was observed between the FDG SUVmax
and accumulation of (111)In-ibritumomab tiuxetan in lesions. A significant
difference in pretherapeutic FDG SUVmax was observed between responders and non
responders, while no significant difference in (111)In-ibritumomab tiuxetan
SUVmax was observed between the two groups. In contrast, voxel distribution of
FDG demonstrated no significant differences in the three heterogeneity indices
between responders and non-responders, while (111)In-ibritumomab tiuxetan
demonstrated skewness of 0.58 +/- 0.16 and 0.73 +/- 0.24 (p < 0.05), kurtosis of
2.39 +/- 0.32 and 2.78 +/- 0.53 (p < 0.02), and AUC-CSH of 0.37 +/- 0.04 and 0.34
+/- 0.05 (p < 0.05) for responders and non-responders. CONCLUSIONS:
Pretherapeutic FDG accumulation was predictive of the tumor response in (90)Y
ibritumomab tiuxetan therapy. The heterogeneity of the intratumoral distribution
rather than the absolute level of (111)In-ibritumomab tiuxetan was correlated
with the tumor response.
PMID- 25853017
TI - The effect of radiation exposure on multidrug resistance: in vitro and in vivo
studies using non-small lung cancer cells.
AB - BACKGROUND: Technetium-99m methoxyisobutylisonitrile (Tc MIBI) is a substrate
with the same uptake kinetics as doxorubicin. Multidrug resistance (MDR) is a
mechanism that impedes chemotherapy of non-small cell lung cancer (NSCLC). We
examined the effect of radiation exposure on MDR in NSCLC and the synergy between
an MDR modulator, GG918, and radiation, using (99m)Tc MIBI in vitro and
doxorubicin in vivo. METHODS: In vitro NSCLC cells (H1299) were exposed to
radiation (3-, 6-, and 9-Gy-irradiated groups) alongside a not-irradiated (0 Gy)
group. Technetium-99 metastable methoxyisobutylisonitrile ((99m)Tc MIBI) was
administered to cell suspensions at 48 h after irradiation. Cell radioactivity
was measured, and C in/C out ratios were calculated and compared. NSCLC cells
were also subcutaneously transplanted into the left thigh of nude mice, which
were subsequently raised for 2 weeks. Two groups of mice were used: mice exposed
to irradiation (9-Gy-irradiated) and those that were not (not-irradiated).
Doxorubicin was administered through the caudal vein at 48 h after the
irradiation. Using an in vivo imaging system, intratumoural photon counts were
measured. To determine the synergy between the MDR modulator and 3- or 6-Gy
irradiation, the final GG918 concentration was determined: 0.1 MUM (N-H, 3-H, and
6-H groups), 0.001 MUM (N-L, 3-L, and 6-L groups), and 0 MUM (N-0, 3-0, and 6-0
groups). C in/C out ratios were calculated and compared among the groups.
RESULTS: C in/C out after 6- or 9-Gy irradiation was significantly higher than
that of the not-irradiated group (0 Gy). In vivo, fluorescence photon counts were
significantly higher in the tumours of 9-Gy-irradiated mice, up to 270 min after
administration of doxorubicin, as compared to the not-irradiated mice. The C in/C
out ratio in the N-H, 3-H, and 6-H groups was significantly higher than that in
the N-0, 3-0, and 6-0 groups. There was no significant difference between C in/C
out in the N-L group and that of the N-0 group. However, the C in/C out ratio in
the 3-L and 6-L groups was significantly higher than that in the 3-0 and 6-0
groups. CONCLUSIONS: Irradiation decreased MDR in NSCLC cells. In combination
with a low-dose MDR modulator, GG918, MDR transport function was synergistically
reduced 48 h post-irradiation.
PMID- 25853018
TI - The diagnostic accuracy of dopamine transporter SPECT imaging to detect
nigrostriatal cell loss in patients with Parkinson's disease or clinically
uncertain parkinsonism: a systematic review.
AB - In specialized movement disorder centers, Parkinson's disease (PD) is wrongly
diagnosed in 6 to 25% of cases. To improve the accuracy of the clinical
diagnosis, it is necessary to have a reliable and practical reference standard.
Dopamine transporter single-photon emission computed tomography (DAT SPECT)
imaging might have the potential (high diagnostic accuracy and practical to use)
to act as reference standard in detecting nigrostriatal cell loss in patients
with (early stage) parkinsonism. We performed a systematic review to evaluate if
DAT SPECT imaging can be used as such. Relevant studies were searched in the
MEDLINE and EMBASE databases. Studies were selected when they met the following
criteria: (1) all patients were adults with a clinical diagnosis of PD or
clinically uncertain parkinsonism and (2) the study reported original data. In
addition, studies needed to fulfill one of the two following criteria: (1)
patients underwent at least one DAT SPECT and had a neuropathological confirmed
diagnosis and (2) patients underwent at least two DAT SPECT scans, performed at
least 2 years apart. The search identified 1,649 articles. Eight studies
fulfilled our selection criteria and were included in this review. There was only
one study including patients with diagnostic uncertainty. Sensitivity and
specificity of DAT SPECT imaging to detect nigrostriatal cell loss were 98%. The
other studies included patients with a diagnosis of PD in whom there was no
uncertainty. In these studies, sensitivity was 100%. Our systematic review
indicates that DAT SPECT imaging seems to be accurate to detect nigrostriatal
cell loss in patients with parkinsonism.
PMID- 25853019
TI - [(18)F]FDG-6-P as a novel in vivo tool for imaging staphylococcal infections.
AB - BACKGROUND: Management of infection is a major clinical problem. Staphylococcus
aureus is a Gram-positive bacterium which colonises approximately one third of
the adult human population. Staphylococcal infections can be life-threatening and
are frequently complicated by multi-antibiotic resistant strains including
methicillin-resistant S. aureus (MRSA). Fluorodeoxyglucose ([(18)F]FDG) imaging
has been used to identify infection sites; however, it is unable to distinguish
between sterile inflammation and bacterial load. We have modified [(18)F]FDG by
phosphorylation, producing [(18)F]FDG-6-P to facilitate specific uptake and
accumulation by S. aureus through hexose phosphate transporters, which are not
present in mammalian cell membranes. This approach leads to the specific uptake
of the radiopharmaceutical into the bacteria and not the sites of sterile
inflammation. METHODS: [(18)F]FDG-6-P was synthesised from [(18)F]FDG. Yield,
purity and stability were confirmed by RP-HPLC and iTLC. The specificity of
[(18)F]FDG-6-P for the bacterial universal hexose phosphate transporter (UHPT)
was confirmed with S. aureus and mammalian cell assays in vitro. Whole body
biodistribution and accumulation of [(18)F]FDG-6-P at the sites of bioluminescent
staphylococcal infection were established in a murine foreign body infection
model. RESULTS: In vitro validation assays demonstrated that [(18)F]FDG-6-P was
stable and specifically transported into S. aureus but not mammalian cells.
[(18)F]FDG-6-P was elevated at the sites of S. aureus infection in vivo compared
to uninfected controls; however, the increase in signal was not significant and
unexpectedly, the whole-body biodistribution of [(18)F]FDG-6-P was similar to
that of [(18)F]FDG. CONCLUSIONS: Despite conclusive in vitro validation,
[(18)F]FDG-6-P did not behave as predicted in vivo. However at the site of known
infection, [(18)F]FDG-6-P levels were elevated compared with uninfected controls,
providing a higher signal-to-noise ratio. The bacterial UHPT can transport hexose
phosphates other than glucose, and therefore alternative sugars may show
differential biodistribution and provide a means for specific bacterial
detection.
PMID- 25853020
TI - A comparative PET imaging study with the reversible and irreversible EGFR
tyrosine kinase inhibitors [(11)C]erlotinib and [(18)F]afatinib in lung cancer
bearing mice.
AB - BACKGROUND: Tyrosine kinase inhibitors (TKIs) have experienced a tremendous boost
in the last decade, where more than 15 small molecule TKIs have been approved by
the FDA. Unfortunately, despite their promising clinical successes, a large
portion of patients remain unresponsive to these targeted drugs. For non-small
cell lung cancer (NSCLC), the effectiveness of TKIs is dependent on the
mutational status of epidermal growth factor receptor (EGFR). The exon 19
deletion as well as the L858R point mutation lead to excellent sensitivity to
TKIs such as erlotinib and gefitinib; however, despite initial good response,
most patients invariably develop resistance against these first-generation
reversible TKIs, e.g., via T790M point mutation. Second-generation TKIs that
irreversibly bind to EGFR wild-type and mutant isoforms have therefore been
developed and one of these candidates, afatinib, has now reached the market.
Whether irreversible TKIs differ from reversible TKIs in their in vivo tumor
targeting properties is, however, not known and is the subject of the present
study. METHODS: Erlotinib was labeled with carbon-11 and afatinib with fluorine
18 without modifying the structure of these compounds. A preclinical positron
emission tomography (PET) study was performed in mice bearing NSCLC xenografts
with a representative panel of mutations: an EGFR-WT xenograft cell line (A549),
an acquired treatment-resistant L858R/T790M mutant (H1975), and a treatment
sensitive exon 19 deleted mutant (HCC827). PET imaging was performed in these
xenografts with both tracers. Additionally, the effect of drug efflux transporter
permeability glycoprotein (P-gp) on the tumor uptake of tracers was explored by
therapeutic blocking with tariquidar. RESULTS: Both tracers only demonstrated
selective tumor uptake in the HCC827 xenograft line (tumor-to-background ratio,
[(11)C]erlotinib 1.9 +/- 0.5 and [(18)F]afatinib 2.3 +/- 0.4), thereby showing
the ability to distinguish sensitizing mutations in vivo. No major differences
were observed in the kinetics of the reversible and the irreversible tracers in
each of the xenograft models. Under P-gp blocking conditions, no significant
changes in tumor-to-background ratio were observed; however, [(18)F]afatinib
demonstrated better tumor retention in all xenograft models. CONCLUSIONS: TKI-PET
provides a method to image sensitizing mutations and can be a valuable tool to
compare the distinguished targeting properties of TKIs in vivo.
PMID- 25853021
TI - Evaluation of elastix-based propagated align algorithm for VOI- and voxel-based
analysis of longitudinal (18)F-FDG PET/CT data from patients with non-small cell
lung cancer (NSCLC).
AB - BACKGROUND: Deformable image registration allows volume of interest (VOI)- and
voxel-based analysis of longitudinal changes in fluorodeoxyglucose (FDG) tumor
uptake in patients with non-small cell lung cancer (NSCLC). This study evaluates
the performance of the elastix toolbox deformable image registration algorithm
for VOI and voxel-wise assessment of longitudinal variations in FDG tumor uptake
in NSCLC patients. METHODS: Evaluation of the elastix toolbox was performed using
(18)F-FDG PET/CT at baseline and after 2 cycles of therapy (follow-up) data in
advanced NSCLC patients. The elastix toolbox, an integrated part of the IMALYTICS
workstation, was used to apply a CT-based non-linear image registration of follow
up PET/CT data using the baseline PET/CT data as reference. Lesion statistics
were compared to assess the impact on therapy response assessment. Next, CT-based
deformable image registration was performed anew on the deformed follow-up PET/CT
data using the original follow-up PET/CT data as reference, yielding a realigned
follow-up PET dataset. Performance was evaluated by determining the correlation
coefficient between original and realigned follow-up PET datasets. The intra- and
extra-thoracic tumors were automatically delineated on the original PET using a
41% of maximum standardized uptake value (SUVmax) adaptive threshold. Equivalence
between reference and realigned images was tested (determining 95% range of the
difference) and estimating the percentage of voxel values that fell within that
range. RESULTS: Thirty-nine patients with 191 tumor lesions were included. In
37/39 and 12/39 patients, respectively, thoracic and non-thoracic lesions were
evaluable for response assessment. Using the EORTC/SUVmax-based criteria, 5/37
patients had a discordant response of thoracic, and 2/12 a discordant response of
non-thoracic lesions between the reference and the realigned image. FDG uptake
values of corresponding tumor voxels in the original and realigned reference PET
correlated well (R (2)=0.98). Using equivalence testing, 94% of all the voxel
values fell within the 95% range of the difference between original and realigned
reference PET. CONCLUSIONS: The elastix toolbox impacts lesion statistics and
therefore therapy response assessment in a clinically significant way. The
elastix toolbox is therefore not applicable in its current form and/or standard
settings for PET response evaluation. Further optimization and validation of this
technique is necessary prior to clinical implementation.
PMID- 25853022
TI - Optimisation of quantitative lung SPECT applied to mild COPD: a software phantom
simulation study.
AB - BACKGROUND: The amount of inhomogeneities in a (99m)Tc Technegas single-photon
emission computed tomography (SPECT) lung image, caused by reduced ventilation in
lung regions affected by chronic obstructive pulmonary disease (COPD), is
correlated to disease advancement. A quantitative analysis method, the CVT
method, measuring these inhomogeneities was proposed in earlier work. To detect
mild COPD, which is a difficult task, optimised parameter values are needed.
METHODS: In this work, the CVT method was optimised with respect to the parameter
values of acquisition, reconstruction and analysis. The ordered subset
expectation maximisation (OSEM) algorithm was used for reconstructing the lung
SPECT images. As a first step towards clinical application of the CVT method in
detecting mild COPD, this study was based on simulated SPECT images of an
advanced anthropomorphic lung software phantom including respiratory and cardiac
motion, where the mild COPD lung had an overall ventilation reduction of 5%.
RESULTS: The best separation between healthy and mild COPD lung images as
determined using the CVT measure of ventilation inhomogeneity and 125 MBq (99m)Tc
was obtained using a low-energy high-resolution collimator (LEHR) and a power 6
Butterworth post-filter with a cutoff frequency of 0.6 to 0.7 cm(-1). Sixty-four
reconstruction updates and a small kernel size should be used when the whole lung
is analysed, and for the reduced lung a greater number of updates and a larger
kernel size are needed. CONCLUSIONS: A LEHR collimator and 125 (99m)Tc MBq
together with an optimal combination of cutoff frequency, number of updates and
kernel size, gave the best result. Suboptimal selections of either cutoff
frequency, number of updates and kernel size will reduce the imaging system's
ability to detect mild COPD in the lung phantom.
PMID- 25853023
TI - Fluorescence-guided development of a tricistronic vector encoding bimodal optical
and nuclear genetic reporters for in vivo cellular imaging.
AB - BACKGROUND: In vivo imaging using genetic reporters is a central supporting tool
in the development of cell and gene therapies affording us the ability to
selectively track the therapeutic indefinitely. Previous studies have
demonstrated the utility of the human norepinephrine transporter (hNET) as a
positron emission tomography/single photon emission computed tomography
(PET/SPECT) genetic reporter for in vivo cellular imaging. Here, our aim was to
extend on this work and construct a tricistronic vector with dual optical
(firefly luciferase) and nuclear (hNET) in vivo imaging and ex vivo histochemical
capabilities. Guiding this development, we describe how a fluorescent substrate
for hNET, 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP(+)), can be used to
optimise vector design and serve as an in vitro functional screen. METHODS:
Vectors were designed to co-express a bright red-shifted firefly luciferase
(FLuc), hNET and a small marker gene RQR8. Genes were co-expressed using 2A
peptide linkage, and vectors were transduced into a T cell line, SupT1. Two
vectors were constructed with different gene orientations; FLuc.2A.RQR8.2A.hNET
and hNET.2A.FLuc.2A.RQR8. hNET function was assessed using ASP(+)-guided flow
cytometry. In vivo cellular conspicuity was confirmed using sequential
bioluminescence imaging (BLI) and SPECT imaging of transduced SupT1 cells
injected into the flanks of mice. RESULTS: SupT1/FLuc.2A.RQR8.2A.hNET cells
resulted in >4-fold higher ASP(+) uptake compared to SupT1/hNET.2A.FLuc.2A.RQR8,
suggesting that 2A orientation effected hNET function. SupT1/FLuc.2A.RQR8.2A.hNET
cells were readily visualised with both BLI and SPECT, demonstrating high signal
to noise at 24 h post (123)I-meta-iodobenzylguanidine (MIBG) administration.
CONCLUSIONS: In this study, a pre-clinical tricistronic vector with flow
cytometry, BLI, SPECT and histochemical capabilities was constructed, which can
be widely applied in cell tracking studies supporting the development of cell
therapies. The study further demonstrates that hNET function in engineered cells
can be assessed using ASP(+)-guided flow cytometry in place of costly
radiosubstrate methodologies. This fluorogenic approach is unique to the hNET
PET/SPECT reporter and may prove valuable when screening large numbers of cell
lines or vector/mutant constructs.
PMID- 25853024
TI - Reconstruction of productivity signal and deep-water conditions in Moroccan
Atlantic margin (~35 degrees N) from the last glacial to the Holocene.
AB - In order to assess the changes in sea-surface hydrology and productivity signal
from the last glacial to the Holocene; a set of isotopic, geochemical and
microgranulometric proxies was used for this study. Former studies revealed that
the reconstruction of paleoproductivity from ocean sediment gives different
results depending the measurement used. The comparison between our productivity
proxies (total organic carbon, carbonate and planktonic delta(13)C) as well as
previous results in nearby location indicates that the planktonic delta(13)C
responds better to marine productivity changes and represents therefore a
suitable proxy for paleoproductivity reconstruction in our studied area. The
productivity signal reveals two main enrichments during the Young Dryas (YD) and
the Heinrich Event 1 (HE 1) and correlates perfectly with upwelling activity
mentioned by an increasing trend of aeolian proxies. In addition, our results
show that biogenic components in the sediment have a marine origin and the
proportion of organic matter preserved depends on the total sediment accumulation
rate.
PMID- 25853025
TI - Case study to assess the safety of irreversible electroporation near the heart.
AB - INTRODUCTION: Irreversible electroporation (IRE) is a promising technique for the
focal treatment of soft tissue tumors. Even though the local application of an
excessive electric field is a potential cause of cardiac arrhythmias, initial
clinical studies have shown that IRE is generally safe when cardiac gating is
employed. CASE DESCRIPTION: In this case report, we observed an episode of
ventricular extrasystoles without hemodynamic changes during which time the
synchronization device failed to operate properly, with pulses delivered not in
the absolute refractory period but in the relative refractory period. DISCUSSION
AND EVALUATION: At present, persons performing IRE must keep in mind that there
is a small but real risk of synchronization failure even when a cardiac
synchronization device is used. CONCLUSION: It is advisable to err on the side of
caution when treating lesions near the heart.
PMID- 25853026
TI - Iron, manganese, cadmium, chromium, zinc and arsenic groundwater contents of
Agbor and Owa communities of Nigeria.
AB - Iron, manganese, zinc, cadmium, and chromium heavy metals and arsenic contents of
groundwater in area and surrounding environment, of Ika land in the Delta state,
Nigeria was studied. Groundwater without any treatment is the predominant source
of drinking water by inhabitants of these communities. However, the quality of
this water source is not immediately known, raising questions of its safety.
Results of a regional composite of groundwater obtained, shows high iron (27%)
and zinc (36%) contents in Boji-Boji Agbor area, manganese (31%) was highest in
Boji-Boji Owa. Alihame recorded the lowest value of zinc (8%), while manganese
was lowest in Agbor Obi area (12%). Arsenic, cadmium, and chromium were below
detection limit in all the sample sites. Correlational matrix analysis revealed
no significant relationships between metal types studied. Analyses of chronic
daily dose intake (CDI), and hazard index were all very low. A hazard index of
0.01 was obtained. One-way ANOVA show significant statistical difference in the
mean concentrations of the heavy metals for the different sample sites, which
indicate that different sites contribute differently to the mean concentrations
of the groundwater in the study area. Four conclusions are drawn from this study.
Indications are that the heavy metals present in the Nigerian aquifer are very
much below the maximum concentration levels and guideline values of national and
WHO standards. Secondly, there is a heavier load of these metals in the city
centre than in the suburbs; with Boji-Boji area Agbor/Owa urban areas accounting
for 27 and 20 percent of load respectively. Thirdly, the below detection limit
results for some of the metal ions and the very low concentrations of those
detected are pointers to the absence of industrial activities and mining.
Finally, the groundwater in the study area is considered to be generally safe
with respect to the contaminants studied and results posted for the composite
samples. Inhabitants are therefore under no illusion of immediate or remote
health challenges with regards to the heavy metals analyzed. More individual
sampling, however, is recommended.
PMID- 25853027
TI - Selective pruning in pineapple plants as means to reduce heterogeneity in fruit
quality.
AB - Heterogeneity in fruit quality (size and taste) is a major problem in pineapple
production chains. The possibilities were investigated of reducing the
heterogeneity in pineapple in the field by pruning slips on selected plants, in
order to promote the fruit growth on these plants. Slips are side shoots that
develop just below the pineapple fruit during fruit development. Two on-farm
experiments were carried out in commercial fields in Benin with a cultivar
locally known as Sugarloaf, to determine (a) the effect of slip pruning on fruit
quality; (b) whether the effect of slip pruning depends on the pruning time; and
(c) whether slip pruning from the plants with the smallest infructescences
results in more uniformity in fruit quality. A split-plot design was used with
pruning time (2 or 3 months after inflorescence emergence) as main factor and
fraction of pruned plants (no plants pruned (control); pruning on the one-third
plants with the smallest infructescences; pruning on the two-thirds plants with
the smallest infructescences; pruning on all plants) as sub-factor. Fruit quality
characteristics measured at harvest were the fruit (infructescence + crown)
weight and length, the infructescence weight and length, the crown weight and
length, the ratio crown length: infructescence length, the total soluble solids,
the juice pH and the flesh translucency. Results indicated that pruning of slips
of any fraction of the plants at 2 or 3 months after inflorescence emergence did
not lead to a consistent improvement in quality or uniformity. Consequently it is
not recommended to farmers in Benin to prune the slips.
PMID- 25853028
TI - A population-based analysis of outcomes for small cell carcinoma of the breast by
tumor stage and the use of radiation therapy.
AB - PURPOSE: Primary small cell carcinomas of the breast (SCCB) are rare tumors with
limited data on outcomes and treatment strategies. Using a population based
approach, we aimed to study outcomes of SCCB and determine whether the use of
radiation therapy is associated with better survival among patients with SCCB.
METHODS: Using the Surveillance, Epidemiology and End Results (SEER) registry, we
identified patients with SCCB between1973 and 2010. We examined the stage
specific survival of these patients and compared it to the stage specific
survival of small cell lung cancer (SCLC) from the SEER database over the same
accrual period. We further analyzed the impact of radiation therapy on overall
survival for SCCB patients using a univariate and multivariate approach. RESULTS:
A total of 199 patients with primary SCCB with staging were identified during the
study period. Eighty-four patients (42%) had localized disease, 77 (39%) had
regional disease and 38 (19%) had distant disease. For comparison, 81,933
patients with SCLC were identified. Outcomes were superior for patients with SCCB
with localized (150 vs. 16 months, p < 0.01) and regional disease (56 vs. 13
months, p < 0.01), but not distant disease (7 vs. 7 months, p = 0.43). Use of
radiation therapy was not associated with a significant difference in OS for
patients with either localized (202 vs. 147 months, p = 0.48) or regional (52 vs.
75 months, p = 0.650) disease. CONCLUSIONS: SCCB has a more favorable prognosis
by stage for localized and regional disease than SCLC. Adjuvant radiation is not
associated with an improvement in survival for patients with localized or
regional SCCB in this dataset.
PMID- 25853029
TI - Finite element/percolation theory modelling of the micromechanical behavior of
clayey soils.
AB - A hybrid model for soils, which combines percolation theory and finite element
method is presented. The internal soil structure is modelled via the finite
element method, and percolation networks are used for analyzing its mechanical
behaviour. Through a microscopic characterization of elastic properties of soil
grains, the model is generated. The effective percolation threshold obtained is
lower than that of the network geometric percolation. The effective mechanical
properties predicted are successfully compared to published experimental results.
PMID- 25853031
TI - Within field spatial variation in methane emissions from lowland rice in Myanmar.
AB - An assessment of within field spatial variations in grain yield and methane (CH4)
emission was conducted in lowland rice fields of Myanmar. Two successive rice
fields (1(st) field and 2(nd) field) were divided into fertilized and non
fertilized parts and CH4 measurements were conducted at the inlet, middle and
outlet positions of each field. The results showed that CH4 emissions at non
fertilized parts were higher than those at fertilized part in both rice fields.
The average CH4 emissions ranged from 8.7 to 26.6 mg m(-2) h(-1) in all positions
in both rice fields. The spatial variation in CH4 emission among the positions
was high in both rice fields with the highest emissions in the outlet of the
1(st) field and the inlet of the 2(nd) field. The CH4 emissions at these two
positions showed 2 - 2.5 times higher than those at other positions in both rice
fields. Stepwise regression analysis indicates that soil total carbon content is
the primary factor for CH4 emission. The average CH4 emissions during rice
growing season were 13.5 mg m(-2) h(-1) for the 1(st) field and 15.7 mg m(-2) h(
1) for the 2(nd) field. Spearman rank order correlation analysis showed that CH4
emission was significantly and positively correlated with soil temperature,
surface water depth and negatively correlated with soil redox potential. The
result indicated that high within field spatial variation in CH4 emissions
required different site specific management practices to mitigate CH4 emissions
in lowland paddy rice soil.
PMID- 25853030
TI - Effects of six months of Yoga on inflammatory serum markers prognostic of
recurrence risk in breast cancer survivors.
AB - Yoga-based exercise has proven to be beneficial for practitioners, including
cancer survivors. This study reports on the effect on inflammatory biological
markers for 20 breast cancer survivors who participated in a six-month yoga-based
(YE) exercise program. Results are compared to a comprehensive exercise (CE)
program group and a comparison (C) exercise group who chose their own exercises.
"Pre" and "post" assessments included measures of anthropometrics,
cardiorespiratory capacity, and inflammatory markers interleukin 6 (IL-6),
interleukin 8 (IL-8), tumor necrosis factor alpha (TNFalpha) and C-reactive
protein (CRP). Descriptive statistics, effect size (d), and dependent sample 't'
tests for all outcome measures were calculated for the YE group. Significant
improvements were seen in decreased % body fat, (-3.00%, d = -0.44, p = <.001)
but not in cardiorespiratory capacity or in inflammatory serum markers. To
compare YE outcomes with the other two groups, a one-way analysis of co-variance
(ANCOVA) was used, controlling for age, BMI, cardiorespiratory capacity and serum
marker baseline values. We found no differences between groups. Moreover, we did
not see significant changes in any inflammatory marker for any group. Our results
support the effectiveness of yoga-based exercise modified for breast cancer
survivors for improving body composition. Larger studies are needed to determine
if there are significant changes in inflammatory serum markers as a result of
specific exercise modalities.
PMID- 25853033
TI - An emergentist vs a linear approach to social change processes: a gender look in
contemporary India between modernity and Hindu tradition.
AB - Using Census of India data from 1901 to 2011 and national and international
reports on women's condition in India, beginning with sex ratio trends according
to regional distribution up to female infanticides and sex-selective abortions
and dowry deaths, this study examines the sociological aspects of the gender
imbalance in modern contemporary India. Gender inequality persistence in India
proves that new values and structures do not necessarily lead to the
disappearance of older forms, but they can co-exist with mutual adaptations and
reinforcements. Data analysis suggests that these unexpected combinations are not
comprehensible in light of a linear concept of social change which is founded, in
turn, on a concept of social systems as linear interaction systems that relate to
environmental perturbations according to proportional cause and effect
relationships. From this perspective, in fact, behavioral attitudes and
interaction relationships should be less and less proportionally regulated by
traditional values and practices as exposure to modernizing influences increases.
And progressive decreases should be found in rates of social indicators of gender
inequality like dowry deaths (the inverse should be found in sex ratio trends).
However, data does not confirm these trends. This finding leads to emphasize a
new theoretical and methodological approach toward social systems study, namely
the conception of social systems as complex adaptive systems and the
consequential emergentist, nonlinear conception of social change processes.
Within the framework of emergentist theory of social change is it possible to
understand the lasting strength of the patriarchal tradition and its problematic
consequences in the modern contemporary India.
PMID- 25853032
TI - Expression and functional validation of heat-labile enterotoxin B (LTB) and
cholera toxin B (CTB) subunits in transgenic rice (Oryza sativa).
AB - We expressed the heat-labile enterotoxin B (LTB) subunit from enterotoxigenic
Escherichia coli and the cholera toxin B (CTB) subunit from Vibrio cholerae under
the control of the rice (Oryza sativa) globulin (Glb) promoter. Binding of
recombinant LTB and CTB proteins was confirmed based on GM1-ganglioside binding
enzyme-linked immunosorbent assays (GM1-ELISA). Real-time PCR of three
generations (T3, T4, and T5) in homozygous lines (LCI-11) showed single copies of
LTB, CTB, bar and Tnos. LTB and CTB proteins in rice transgenic lines were
detected by Western blot analysis. Immunogenicity trials of rice-derived CTB and
LTB antigens were evaluated through oral and intraperitoneal administration in
mice, respectively. The results revealed that LTB- and CTB-specific IgG levels
were enhanced in the sera of intraperitoneally immunized mice. Similarly, the
toxin-neutralizing activity of CTB and LTB in serum of orally immunized mice was
associated with elevated levels of both IgG and IgA. The results of the present
study suggest that the combined expression of CTB and LTB proteins can be
utilized to produce vaccines against enterotoxigenic strains of Escherichia coli
and Vibrio cholera, for the prevention of diarrhea.
PMID- 25853034
TI - In-home occupational therapy for a patient with stage IV lung cancer: changes in
quality of life and analysis of causes.
AB - INTRODUCTION: We tracked and analyzed the changes in the quality of life (QOL) of
a stage 4 lung cancer patient receiving occupational therapy at home. CASE
DESCRIPTION: In a longitudinal study consisting of 4 evaluations over 9 months, a
66-year-old female with lung cancer was assessed using the Philadelphia Geriatric
Center (PGC) Morale Scale and the 100-Point Satisfaction Scale. The QOL scores
over time and factors influencing changes in these scores were analyzed.
DISCUSSION AND EVALUATION: A histogram of QOL scores demonstrated a rapid
increase followed by a mild decrease and then stable level. Interviews revealed
the patient's response to knowing her life expectancy, meeting a qualified
occupational therapist, increasing her leisure activity, changing her family
relationships and facing the prospect of death. We also confirmed that
occupational therapy, such as writing letters or keeping a diary, reminded her of
her late parents, hometown and childhood and helped her accept death.
CONCLUSIONS: For a terminal lung cancer patient, meeting an occupational
therapist to discuss fear or self-loathing improved QOL. Further, an active
lifestyle played an important role in helping the patient accept death and lead a
peaceful and stable life.
PMID- 25853035
TI - Study of circulating IgG antibodies to peptide antigens derived from BIRC5 and
MYC in cervical cancer.
AB - The present study was undertaken to detect circulating IgG antibodies to peptide
antigens derived from baculoviral IAP repeat-containing protein 5 isoform 2
(BIRC5) and myc proto-oncogene protein (MYC) in cervical cancer. A total of 107
female patients with cervical cancer of stages I and II, and 130 healthy female
subjects were recruited for analysis of circulating IgG antibodies to BIRC5 and
MYC. Student's t-test showed significant differences in circulating levels of
anti-BIRC5 IgG (t = -4.27, df = 235, P < 0.0001) and anti-MYC IgG (t = 3.51, df =
232, P = 0.0005) between the patient group and the control group. Receiver
operating characteristic (ROC) analysis showed an area under the ROC curve (AUC)
of 0.67 with sensitivity of 23.4% against specificity of 90% for the anti-BIRC5
IgG assay and an AUC of 0.66 with sensitivity of 9.4% against specificity of
90.6% for the anti-MYC IgG assay. Analysis of quality control samples gave an
inter-assay deviation of 8.9% in the anti-BIRC5 IgG assay and 9.0% in the anti
MYC IgG assay. This work suggests that anti-BIRC5 IgG could serve as a biomarker
for early diagnosis of cervical cancer although a panel of such tumor-associated
antigens is needed to develop a highly sensitive test.
PMID- 25853036
TI - Design and evaluation of a peptide-based immunotoxin for breast cancer
therapeutics.
AB - Immunotoxins are chimeric proteins comprising a specific cellular targeting
domain linked to a cytotoxic factor. Here we describe the design and use of a
novel, peptide-based immunotoxin that can initiate selective cytotoxicity on
ErbB2-positive cells. ErbB2 is a receptor tyrosine kinase that is overexpressed
in the tumor cells of approximately 30% of breast cancer patients. Immunotoxin
candidates were designed to incorporate a targeting ligand with affinity for
ErbB2 along with a membrane lysin-based toxin domain. One particular peptide
candidate, NL1.1-PSA, demonstrated selective cytotoxicity towards ErbB2
overexpressing cell lines. We utilized a bioengineering strategy to show that
recombinant NL1.1-PSA immunotoxin expression by Escherichia coli also conferred
selective cytotoxicity towards ErbB2-overexpressing cells. Our findings hold
significant promise for the use of effective immunotoxins in cancer therapeutics.
PMID- 25853039
TI - Nano-science and dentistry.
PMID- 25853037
TI - Biochemical and spectroscopic properties of Brucella microti glutamate
decarboxylase, a key component of the glutamate-dependent acid resistance system.
AB - In orally acquired bacteria, the ability to counteract extreme acid stress (pH ?
2.5) ensures survival during transit through the animal host stomach. In several
neutralophilic bacteria, the glutamate-dependent acid resistance system (GDAR) is
the most efficient molecular system in conferring protection from acid stress. In
Escherichia coli its structural components are either of the two glutamate
decarboxylase isoforms (GadA, GadB) and the antiporter, GadC, which imports
glutamate and exports gamma-aminobutyrate, the decarboxylation product. The
system works by consuming protons intracellularly, as part of the decarboxylation
reaction, and exporting positive charges via the antiporter. Herein, biochemical
and spectroscopic properties of GadB from Brucella microti (BmGadB), a Brucella
species which possesses GDAR, are described. B. microti belongs to a group of
lately described and atypical brucellae that possess functional gadB and gadC
genes, unlike the most well-known "classical" Brucella species, which include
important human pathogens. BmGadB is hexameric at acidic pH. The pH-dependent
spectroscopic properties and activity profile, combined with in silico sequence
comparison with E. coli GadB (EcGadB), suggest that BmGadB has the necessary
structural requirements for the binding of activating chloride ions at acidic pH
and for the closure of its active site at neutral pH. On the contrary, cellular
localization analysis, corroborated by sequence inspection, suggests that BmGadB
does not undergo membrane recruitment at acidic pH, which was observed in EcGadB.
The comparison of GadB from evolutionary distant microorganisms suggests that for
this enzyme to be functional in GDAR some structural features must be preserved.
PMID- 25853038
TI - Impaired respiratory function in MELAS-induced pluripotent stem cells with high
heteroplasmy levels.
AB - Mitochondrial diseases are heterogeneous disorders, caused by mitochondrial
dysfunction. Mitochondria are not regulated solely by nuclear genomic DNA but by
mitochondrial DNA. It is difficult to develop effective therapies for
mitochondrial disease because of the lack of mitochondrial disease models.
Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like
episodes (MELAS) is one of the major mitochondrial diseases. The aim of this
study was to generate MELAS-specific induced pluripotent stem cells (iPSCs) and
to demonstrate that MELAS-iPSCs can be models for mitochondrial disease. We
successfully established iPSCs from the primary MELAS-fibroblasts carrying 77.7%
of m.3243A>G heteroplasmy. MELAS-iPSC lines ranged from 3.6% to 99.4% of
m.3243A>G heteroplasmy levels. The enzymatic activities of mitochondrial
respiratory complexes indicated that MELAS-iPSC-derived fibroblasts with high
heteroplasmy levels showed a deficiency of complex I activity but MELAS-iPSC
derived fibroblasts with low heteroplasmy levels showed normal complex I
activity. Our data indicate that MELAS-iPSCs can be models for MELAS but we
should carefully select MELAS-iPSCs with appropriate heteroplasmy levels and
respiratory functions for mitochondrial disease modeling.
PMID- 25853040
TI - Glucometric assessment of gingival crevicular blood in diabetic and non-diabetic
patients: A randomized clinical trial.
AB - BACKGROUND: Diabetes mellitus is one of the most incessant metabolic afflictions
with high prevalence rate in Indians. Diagnosis of diabetics in the initial stage
helps to prevent its long term complications that are responsible for high
morbidity and mortality. The aim of the present study was to assess whether
glucometric analysis using Gingival Crevicular Blood (GCB) can be used for
screening of diabetic patients in dental chair. MATERIALS AND METHODS: Present
study was a double blinded randomized controlled trial. A total of 50 patients,
25 diabetic and 25 non-diabetic with chronic periodontitis were enrolled in the
study. Blood oozing from the gingival crevices after periodontal pocket probing
of anterior teeth and Finger Prick Blood (FPB) was taken and analysed by
glucometer. RESULT: Mean +/- S.D was 195.84 +/- 27.19 and 138.78 +/- 29.95 for
GCB and FPB respectively in diabetic group. For non-diabetic group Mean +/- S.D
was 103.84 +/- 12.56 and 84.36 +/- 10.36 respectively for GCB and FPB. A Karl
Pearson correlation coefficient value of r = +0.735 for diabetic and r = +0.802
for non-diabetic group comparing GCB and FPB. CONCLUSION: GCB cannot be used for
screening blood glucose during periodontal examination.
PMID- 25853041
TI - Antibacterial activity of clove, gall nut methanolic and ethanolic extracts on
Streptococcus mutans PTCC 1683 and Streptococcus salivarius PTCC 1448.
AB - INTRODUCTION: Antimicrobial compounds from herbal sources have good therapeutic
potential. In this study, the antibacterial effects of clove and gall nut,
methanolic and ethanolic extractions, were evaluated for their effect on
Streptococcus mutans PTCC 1683 and Streptococcus salivarius PTCC 1448, as both
the two cause oral diseases. METHOD: The clove and gall nut methanolic and
ethanolic extracts were prepared and antibacterial activity was evaluated for S.
mutans and S. salivarius in the base of inhibition zone diameter using agar
diffusion method. In this part minimum inhibitory concentration (MIC) and minimal
bactericidal concentration (MBC) were assessed. RESULTS: These extracts showed
effective antibacterial activity on bacteria. Antibacterial activity of
Methanolic extract of clove was more than that of ethanolic extract, and
ethanolic extracts of gall nut had antibacterial activity more than that of
methanolic extracts. MIC and MBC results for clove methanolic extract were 1.5
mg/ml and 3 mg/ml for S. mutans and 6.25 mg/ml and 12.5 mg/ml for S. salivarius,
respectively. These results for clove ethanolic extracts were 12.5 mg/ml and 25
mg/ml for S. mutans and 25 mg/ml and 50 mg/ml for S. salivarius, respectively.
MIC and MBC results for gall nut methanolic extract were 25 mg/ml and 50 mg/ml
for S. mutans and 12.5 mg/ml and 25 mg/ml for S. salivarius, respectively. These
results for gall nut ethanolic extracts were 3.1 mg/ml and 6.2 mg/ml for S.
mutans and 25 mg/ml and 50 mg/ml for S. salivarius, respectively. DISCUSSION: The
results showed effective antibacterial activity using clove and gall nut
methanolic extracts. If other properties such as tolerance of tissue can also be
studied, these extracts can be used as a mouthwash.
PMID- 25853042
TI - Comparative evaluation of natural antioxidants spirulina and aloe vera for the
treatment of oral submucous fibrosis.
AB - AIM: Oral submucous fibrosis (OSMF) is a high risk premalignant condition
predominantly seen in the Indian subcontinent. The aim of the present study was
to compare the efficacy of spirulina and aloe vera in the management of OSMF.
MATERIAL AND METHODS: 42 subjects with clinico-pathologically diagnosed OSMF were
included in the study and divided equally in 2 groups, Group A (spirulina group)
and Group B (aloe vera group). Group A was administered 500 mg spirulina in 2
divided doses for 3 months and Group B was given 5 mg aloe vera gel to be applied
topically thrice daily for 3 months. Evaluation for different clinical parameters
was done at regular intervals and data was analyzed using the Chi-square test. P
value <0.05 was considered to be statistically significant. RESULTS: The patients
in Group A showed significant clinical improvement in mouth opening and
ulcers/erosions/vesicles (p < 0.05). However, there was no significant
improvement in burning sensation (p = 0.06) and pain associated with the lesion
(p = 0.04) among the 2 groups. CONCLUSION: Both the drugs showed improvement in
the condition; however spirulina can bring about significant clinical
improvements in the symptoms like mouth opening and ulcers/erosion/vesicles.
Thus, spirulina appears to be more promising when compared to aloe vera for the
treatment of OSMF.
PMID- 25853043
TI - Prevalence and predictors of tobacco use among general public of Gorakhpur
district, India.
AB - OBJECTIVES: The present study was undertaken to determine the prevalence and
demographic correlates of tobacco use in the adult population. METHOD: The sample
selection was based on stratified random sampling technique selecting a total of
1635 persons from different parts of Gorakhpur district of Uttar Pradesh, India.
The demographic details of participants along with prevalence of tobacco use were
recorded. RESULTS: The prevalence of tobacco use among the subpopulation studied
was 31.1% for males and 6.1 for females. Both smoking and chewing tobacco were
found to be associated with various demographic parameters. The rural population
showed a higher prevalence of tobacco use among both males and females; the male
smoking prevalence was higher in the urban population (23.0%) than its rural
counterpart (18.1%). Also the prevalence of tobacco use was directly
proportionate to age increasing upto the age of approximately 60 years, then
declined. Stepwise Regression analysis showed gender as the strongest predictor
for smoking followed by area of residence, education and age. Whereas education
was the most significant predictors for chewing tobacco, followed by gender and
age. CONCLUSION: The results of this study clearly indicate an association
between tobacco prevalence and various demographic factors. To reduce the cancer
burden, intervention measures to control tobacco use should specifically target
those socio-demographic predictors of the subpopulation which are more
susceptible to tobacco consumption.
PMID- 25853044
TI - Pre-emptive effect of dexamethasone injection and consumption on post-operative
swelling, pain, and trismus after third molar surgery. A prospective, double
blind and randomized study.
AB - AIM: To evaluate the preventative effect of intravenous 4 mg of dexamethasone and
8 mg oral dexamethasone on post-operative pain, swelling and trismus after the
surgical extraction of mandibular third molars. MATERIALS AND METHODS: A
randomized clinical trial comprised of 200 patients (control group I intravenous
and experimental group II orally) with impacted lower third molars, average age
20.8 years with no local or systemic problems, with bilateral impacted lower
third molars, were operated under local anesthesia. Group I was given 4 mg IV and
group II was given 8 mg orally of dexamethasone 1 h before procedure. The choice
of which side to operate first and the amount of concentration of medication to
use was made randomly and double-blindly. Post-operative pain was evaluated using
a visual analog scale (VAS) and the degree of swelling was evaluated through
facial reference points' variation. The presence of trismus was analyzed through
measurement of the interincisal distance (IID). These assessments were obtained
before the operation and 24 h, 48 h and 7th POD. RESULTS: No significant
difference was found in facial swelling and trismus between IV 4 mg injection and
oral 8 mg consumption after lower third molar surgery (student t test P > 0.05).
The visual analogue scale scores for pain assessment showed no significant
difference between IV injection and oral route of dexamethasone (student t test P
> 0.05). CONCLUSION: Patients can be administered 8 mg oral dexamethasone is as
effective as 4 mg intra venous route without much difference in final outcome at
any given point of time.
PMID- 25853045
TI - The role of salivary caffeine clearance in the diagnosis of chronic liver
disease.
AB - BACKGROUND: Chronic liver diseases (CLD) are quite prevalent throughout the
globe. Its early and correct diagnosis is always a concern among physicians,
especially the residual liver function. For this various substrates like caffeine
are being investigated in body fluids like serum and saliva. Saliva as a study
sample has its own advantages due to its non invasiveness; it can be very useful
study sample. METHODS: 30 Subjects with CLD and 15 healthy controls were
administered 200 mg of caffeine. Subjects classified into severity groups (class
A-mild-n = 9, B-moderate-n = 11, and C-severe-n = 10) based on "Child-pugh
classification" of severity of liver disease. After 17 h of dietary caffeine
restriction and before drug administration, 0 h salivary sample was taken. After
the dose of caffeine, 4 and 16 h saliva sample was taken. Blood sample was taken
from controls only at same time points. These samples were analyzed on semi
automated analyzer using Enzyme Multiplied Immunoassay Technique (EMIT) by
spectrophotometric method. Caffeine clearance values were calculated and results
were statistically analyzed. RESULTS: Significant correlation was found between
serum caffeine clearance and salivary caffeine clearance (SCC). Controls showed
higher mean of SCC value of 1.6 +/- 0.2 ml/min/kg while SCC values of subjects
were less, with mean of 0.5 +/- 0.2 ml/min/kg. Significant correlation was found
between degree of hepatic dysfunction and SCC values. CONCLUSION: Saliva can be
used for diagnosis of CLD and assessment of residual liver function in CLD as
alternative to serum.
PMID- 25853046
TI - Evaluation of effects of a preoperative 2-hour fast with glutamine and
carbohydrate rich drink on insulin resistance in maxillofacial surgery.
AB - INTRODUCTION: The aim of this prospective, randomized, single-blinded study was
to compare the effects of preoperative fast for clear fluids on insulin
resistance and hemodynamic stability on patient undergoing maxillofacial surgery.
METHOD: In this study 20 patients undergoing maxillofacial surgery were
randomized into four groups i.e. - group I patients with standard 08 h fasting
before anesthesia, group-II patients were given 400 ml and 200 ml of water 08 h
and 2 h respectively before anesthesia, group III patients were given 400 ml
water with 50 gms of glucose and 40 gm of glutamine 08 h before anesthesia and
200 ml water with 25 gms of glucose and 10 gm of glutamine 2 h before anesthesia,
group IV patients were given 400 ml water with 50 gms of glucose 08 h before
anesthesia and 200 ml water with 25 gms of glucose 2 h before anesthesia. Blood
samples were collected pre-operatively and post-operatively. RESULTS: Overall
results suggest that Post-operative insulin resistance was greater in control
patients (2.0 [0.3]) compared with the other 3 groups (placebo = 1.8 [0.9]);
glutamine = (1.8 [0.6]); carbohydrate = (1.9 [0.6]). DISCUSSION: This study shows
that shortening of pre-operative fasting time for clear fluids until 2- h prior
to anesthesia may induce a favorable environment for the post-operative course.
In conclusion, Glutamine with carbohydrate drink can be used safely in surgical
patients.
PMID- 25853047
TI - Relationship of the lingual frenum to the mandibular central incisors.
AB - CLINICAL IMPLICATION: The purpose of this study is to record the vertical
distance between anterior attachment of lingual frenum and incisal edge of
mandibular central incisors in dentulous subjects and then determine the mean
vertical distance and to suggest guidelines for positioning of mandibular central
incisors in complete dentures. METHOD: In this study, 150 dentulous subjects (75
males and 75 females) were chosen based on predecided inclusion criteria. A
mandibular cast was obtained from irreversible hydrocolloid impression in
modified stock trays for each subject. All subjects were instructed to elevate
the tongue while the impressions were made. The vertical distance between the
anterior attachment of the lingual frenum and incisal edges of mandibular central
incisors was measured on the casts and then the values were statistically
analyzed. RESULT: The distance between anterior attachment of lingual frenum
(AALF) mesioincisal edge of mandibular central incisor (CI) in male, female and
total (male + female) subjects was measured. In males it ranged from 7.3 to 8.9
mm with mean (+/-SD) 8.29 +/- 0.36 mm while in females it ranged from 7.1 to 9.0
mm with mean (+/-SD) 8.21 +/- 0.38 mm. CONCLUSION: It is believed that the
application of this anatomic relation can provide a reliable point for arranging
and checking the position of the mandibular central incisors for complete
dentures in patients with class I ridge relationship.
PMID- 25853048
TI - Proteomics - The research frontier in periodontics.
AB - Periodontitis is an inflammatory condition resulting from the interplay between
the infectious agents and host factors. Various protein molecules play a vital
role in the initiation, progression and severity of periodontal diseases. The
study of proteins as biomarkers in periodontal diseases has been highlighted
during the last few years. In periodontitis multiple bacteria derived (e.g.
collagen degrading enzymes, elastase like enzymes etc) and host derived mediators
(eg. PGE2, TNF, IL1, IL6, MMP's etc) expressed in the saliva and gingival
crevicular fluid, can be utilized as diagnostic markers for the disease. Another
significant development regarding human genes and proteins has been the discovery
of potential new drugs for the treatment of periodontal diseases. Therefore the
information of the proteins involved in the pathogenesis of periodontal diseases
can be utilized for its diagnosis, prevention and treatment.
PMID- 25853049
TI - Sturge-Weber syndrome - A case report.
AB - Sturge-Weber syndrome (SWS), also called as encephalotrigeminal angiomatosis is
an uncommon congenital neurological disorder & frequent among the neurocutaneous
syndromes specifically with vascular predominance. This disorder is characterized
by facial capillary malformation & other neurological condition. The oral
manifestations are gingival hemangiomatosis restricting to either side in upper
and lower jaw, sometimes bilateral. We report a case of SWS with oral, ocular and
neurological features.
PMID- 25853050
TI - Intestinal coccidiosis of anadromous and landlocked alewives, Alosa
pseudoharengus, caused by Goussia ameliae n. sp. and G. alosii n. sp.
(Apicomplexa: Eimeriidae).
AB - Anadromous alewives, Alosa pseudoharengus, have experienced significant
population level declines caused by factors including habitat destruction.
Alewives occur in two different life histories, anadromous and landlocked forms.
The landlocked alewife evolved from ancestral anadromous populations, resulting
in an exclusively freshwater and phenotypically unique form. The occurrence of
parasites in a host is linked to the environment, making alewives an ideal model
to compare parasitology within a single species with contrasting life histories.
Currently, little information exists on the presence and impacts of parasites in
these fish populations; the present study sets out to better understand
coccidiosis in the threatened anadromous populations and to understand how
coccidian parasites compare in both life history forms. The intestinal coccidian,
Goussia ameliae n. sp., was described infecting the pyloric cecum of 76% and 86%
of young-of-the-year and adult anadromous alewives, respectively, from the
Maurice River, New Jersey, USA. The coccidian was found in landlocked alewife
populations with a prevalence of 92% and 34% in YOY and adult fish, respectively.
An analysis of the small subunit 18S ribosomal RNA gene of G. ameliae from both
life history forms demonstrated that the coccidian had 100% sequence identity,
confirming the same parasite species in both forms. Though genetic analysis
demonstrated G. ameliae to be identical, some differences were observed in
sporulation and morphology of the parasite within the two populations. The
sporocysts in anadromous populations were shorter and wider, and sporulation
timing differed from that of landlocked fish. These differences may either be
attributed to differences in the host type or to the sporulation environment.
Lastly, alewives from landlocked populations were frequently co-infected with a
second coccidian species in the posterior intestine, which occurred at a lower
prevalence. This species, G. alosii n. sp., was described based on morphological
characters of the sporulated oocysts in fresh parasitological preparations.
PMID- 25853052
TI - Parasites of wildlife - Special issue.
PMID- 25853053
TI - Epidemiology and molecular phylogeny of Babesia sp. in Little Penguins Eudyptula
minor in Australia.
AB - Blood parasites are potential threats to the health of penguins and to their
conservation and management. Little penguins Eudyptula minor are native to
Australia and New Zealand, and are susceptible to piroplasmids (Babesia),
hemosporidians (Haemoproteus, Leucocytozoon, Plasmodium) and kinetoplastids
(Trypanosoma). We studied a total of 263 wild little penguins at 20 sites along
the Australian southeastern coast, in addition to 16 captive-bred little
penguins. Babesia sp. was identified in seven wild little penguins, with positive
individuals recorded in New South Wales, Victoria and Tasmania. True prevalence
was estimated between 3.4% and 4.5%. Only round forms of the parasite were
observed, and gene sequencing confirmed the identity of the parasite and
demonstrated it is closely related to Babesia poelea from boobies (Sula spp.) and
B. uriae from murres (Uria aalge). None of the Babesia-positive penguins
presented signs of disease, confirming earlier suggestions that chronic
infections by these parasites are not substantially problematic to otherwise
healthy little penguins. We searched also for kinetoplastids, and despite
targeted sampling of little penguins near the location where Trypanosoma
eudyptulae was originally reported, this parasite was not detected.
PMID- 25853051
TI - Species of Angiostrongylus (Nematoda: Metastrongyloidea) in wildlife: A review.
AB - Twenty-one species of Angiostrongylus plus Angiostrongylus sp. (Nematoda:
Metastrongyloidea) are known currently in wildlife. These occur naturally in
rodents, tupaiids, mephitids, mustelids, procyonids, felids, and canids, and
aberrantly in a range of avian, marsupial and eutherian hosts including humans.
Adults inhabit the pulmonary arteries and right atrium, ventricle and vena cava,
bronchioles of the lung or arteries of the caecum and mesentery. All species pass
first-stage larvae in the faeces of the host and all utilise slugs and/or aquatic
or terrestrial snails as intermediate hosts. Gastropods are infected by ingestion
or penetration of first-stage larvae; definitive hosts by ingestion of gastropods
or gastropod slime. Transmission of at least one species may involve ingestion of
paratenic hosts. Five developmental pathways are identified in these life cycles.
Thirteen species, including Angiostrongylus sp., are known primarily from the
original descriptions suggesting limited geographic distributions. The remaining
species are widespread either globally or regionally, and are continuing to
spread. Small experimental doses of infective larvae (ca. 20) given to normal or
aberrant hosts are tolerated, although generally eliciting a granulomatous
histopathological response; large doses (100-500 larvae) often result in clinical
signs and/or death. Two species, A. cantonensis and A. costaricensis, are
established zoonoses causing neurological and abdominal angiostrongliasis
respectively. The zoonotic potential of A. mackerrasae, A. malaysiensis and A.
siamensis particularly warrant investigation. Angiostrongylus cantonensis occurs
in domestic animals, mammalian and avian wildlife and humans in the metropolitan
areas of Brisbane and Sydney, Australia, where it has been suggested that tawny
frogmouths and brushtail possums may serve as biosentinels. A major conservation
issue is the devastating role A. cantonensis may play around zoos and fauna parks
where captive rearing of endangered species programmes may exist and where Rattus
spp. are invariably a problem.
PMID- 25853054
TI - Evidence for Natural Selection in Nucleotide Content Relationships Based on
Complete Mitochondrial Genomes: Strong Effect of Guanine Content on Separation
between Terrestrial and Aquatic Vertebrates.
AB - The complete vertebrate mitochondrial genome consists of 13 coding genes. We used
this genome to investigate the existence of natural selection in vertebrate
evolution. From the complete mitochondrial genomes, we predicted nucleotide
contents and then separated these values into coding and non-coding regions. When
nucleotide contents of a coding or non-coding region were plotted against the
nucleotide content of the complete mitochondrial genomes, we obtained linear
regression lines only between homonucleotides and their analogs. On every plot
using G or A content purine, G content in aquatic vertebrates was higher than
that in terrestrial vertebrates, while A content in aquatic vertebrates was lower
than that in terrestrial vertebrates. Based on these relationships, vertebrates
were separated into two groups, terrestrial and aquatic. However, using C or T
content pyrimidine, clear separation between these two groups was not obtained.
The hagfish (Eptatretus burgeri) was further separated from both terrestrial and
aquatic vertebrates. Based on these results, nucleotide content relationships
predicted from the complete vertebrate mitochondrial genomes reveal the existence
of natural selection based on evolutionary separation between terrestrial and
aquatic vertebrate groups. In addition, we propose that separation of the two
groups might be linked to ammonia detoxification based on high G and low A
contents, which encode Glu rich and Lys poor proteins.
PMID- 25853055
TI - A facile method for simultaneously measuring neuronal cell viability and neurite
outgrowth.
AB - Neurite outgrowth is an important morphological phenotype of neuronal cells that
correlates with their function and cell health, yet there are limited methods
available for measuring this phenomenon. Current approaches to measuring neurite
outgrowth are laborious and time-consuming, relying largely upon
immunocytochemical staining of neuronal markers (e.g., beta-III tubulin or MAP2)
followed by manual or automated microscopy for image acquisition and analysis.
Here we report the development of a quick and simple dual-color fluorescent dye
based staining method that allows for the simultaneous measurement of neuronal
cell health and relative neurite outgrowth from the same sample. An orangered
fluorescent dye that stains cell membrane surfaces is used as an indirect
reporter of changes in relative neurite outgrowth due to alterations in the
number or length of membrane projections emanating from neuronal cell bodies.
Cell viability is assessed simultaneously via the use of a cell-permeant dye that
is converted by intracellular esterase activity from a non-fluorescent substrate
to a green-fluorescent product. Using Neuroscreen-1 cells (a PC-12 subclone),
primary rat cortex neurons, and human induced pluripotent stem cell (iPSC)
derived neurons, we demonstrate that this multiplex assay allows for rapid
visualization and unbiased, quantitative plate reader analysis of neuronal cell
health and neurite outgrowth.
PMID- 25853056
TI - Association of ADIPOQ, OLR1 and PPARGC1A gene polymorphisms with growth and
carcass traits in Nelore cattle.
AB - In beef cattle farming, growth and carcass traits are important for genetic
breeding programs. Molecular markers can be used to assist selection and increase
genetic gain. The ADIPOQ, OLR1 and PPARGC1A genes are involved in lipid synthesis
and fat accumulation in adipose tissue. The objective of this study was to
identify polymorphisms in these genes and to assess the association with growth
and carcass traits in Nelore cattle. A total of 639 animals were genotyped by PCR
RFLP for rs208549452, rs109019599 and rs109163366 in ADIPOQ, OLR1 and PPARGC1A
gene, respectively. We analyzed the association of SNPs identified with birth
weight, weaning weight, female yearling weight, female hip height, male yearling
weight, male hip height, loin eye area, rump fat thickness, and backfat
thickness. The OLR1 marker was associated with rump fat thickness and weaning
weight (P < 0.05) and the PPARGC1 marker was associated with female yearling
weight.
PMID- 25853057
TI - IRF6 polymorphisms in Mexican patients with non-syndromic cleft lip.
AB - Cleft lip with or without cleft palate (CL/P) is one of the most common birth
defects; it is a multifactorial disease affecting > 1/1,000 live births in
Europe, and its etiology is largely unknown, although it is very likely genetic
and environmental factors contribute to this malformation. Orofacial development
is a complex process involving many genes and signaling pathways. Mutations in
the gene for the interferon regulatory factor 6 (IRF6) cause a hereditary
dominant malformation syndrome including CL/P, and polymorphisms are associated
with non-syndromic CL/P (MIM 119530). Five SNPs at the locus with high
heterozygosity in Caucasian populations were chosen for the present research due
to their very strong association with CL/P. A case-parent trio study was
performed using 292 samples from Mexico. Association with the rs1319435-C/C
genotype (P = 0.02) was found in patients (73) as compared to pseudocontrols
(219), while the genotype rs1319435-T/C was related with protection (P = 0.041)
in the triad design. Significant over-transmission of the G allele for marker
rs2235375 (P = 0.049) was found. Only the TACGT haplotype was diminished in the
affected child, either in single (P = 0.0208) or double (P = 0.0208) dose. The
pairwise analysis showed rs2235543 and rs2235371 were in strong linkage
disequilibrium. These results point to a substantial contribution of IRF6 in the
etiology of non-syndromic CL/P in a sample of the Mexican population.
PMID- 25853058
TI - Mitochondrial COI and nuclear RAG1 DNA sequences and analyses of specimens of the
three morphologically established species in the genus Trichopsis (Perciformes:
Osphronemidae) reveal new/cryptic species.
AB - Air-breathing fish species of the genus Trichopsis have been reported in
Cambodia, Lao PDR, Indonesia, Malaysia, Singapore, Thailand and Vietnam. It is
only in Thailand that all three recognized species (Trichopsis vittata,
Trichopsis schalleri and Trichopsis pumila), as judged by distinct external
features, are found. Cambodia and Lao PDR harbor two species each. The present
work involves first-time DNA sequencing and analysis based on mitochondrial (COI)
and nuclear (RAG1) DNA of numerous specimens of these species and specimens of a
controversial Phetchaburi (Thailand) fish population with a mixed outward
appearance. In addition to confirming the morphologically clear-cut taxonomic
division of the three fish species, our DNA results show that whereas the T.
pumila populations form one single species, there are cryptic species in the T.
vittata and T. schalleri populations and possibly a new one in the latter.
Members of the putative Phetchaburi fish population have been proven to be
hybrids between T. pumila and T. vittata. In addition, a new the phylogenetic
tree indicating ancestral relationships is also presented. This study should
generate further research to find new/cryptic species of the genus Trichopsis in
all countries harboring the fish.
PMID- 25853059
TI - Characterization of KfrA proteins encoded by a plasmid of Paenibacillus popilliae
ATCC 14706(T).
AB - A scaffold obtained from whole-genome shotgun sequencing of Paenibacillus
popilliae ATCC 14706(T) shares partial homology with plasmids found in other
strains of P. popilliae. PCR and sequencing for gap enclosure indicated that the
scaffold originated from a 15,929-bp circular DNA. The restriction patterns of a
plasmid isolated from P. popilliae ATCC 14706(T) were identical to those expected
from the sequence; thus, this circular DNA was identified as a plasmid of ATCC
14706(T) and designated pPOP15.9. The plasmid encodes 17 putative open reading
frames. Orfs 1, 5, 7, 8, and 9 are homologous to Orfs 11, 12, 15, 16, and 17,
respectively. Orf1 and Orf11 are annotated as replication initiation proteins.
Orf8 and Orf16 are homologs of KfrA, a plasmid-stabilizing protein in Gram
negative bacteria. Recombinant Orf8 and Orf16 proteins were assessed for the
properties of KfrA. Indeed, they formed multimers and bound to inverted repeat
sequences in upstream regions of both orf8 and orf16. A phylogenetic tree based
on amino acid sequences of Orf8, Orf16 and Kfr proteins did not correlate with
species lineage.
PMID- 25853060
TI - Association of novel SNPs in the candidate genes affecting caprine milk fatty
acids related to human health.
AB - In the present investigation, 618 milk samples of Sirohi breed of goat were
collected, and analyzed for conjugated linoleic acid (CLA, C18:2) and other fatty
acids. The CLA in studied goat milk samples was 4.87 mg/g of milk fat and C18:2
cis-9, trans-11 contributes 2.9 mg/g of milk fat and trans10 cis12 contributes
0.82 mg/g of milk fat. The saturated fatty acids in the milk accounted for 69.55%
and unsaturated fatty acid accounted for 28.50%. The unsaturated fatty acid was
constituted by monounsaturated fatty acid (24.57%) and polyunsaturated fatty
acids (3.96%.). The major contribution (45.56%) in total fatty acid was of C12:0,
C14:0 and C16:0. C18:0 and short chain ones (C4:0, C6:0, C8:0, and C10:0) have a
neutral or cholesterol-decreasing effect. The DNA sequence analysis of the genes
(DGAT1, SCAP, PPARG, OLR, FABP3 and PRL) in a random panel of 8 Sirohi goats
revealed 38 SNPs across the targeted regions. Out of the studied SNPs (38) across
these genes, 22 SNPs had significant effect on one or a group of fatty acids
including CLA. The genotypes at these loci showed significant differences in the
least square means of a particular fatty acid or a group of fatty acids including
CLA and its isomers.
PMID- 25853061
TI - KIR genotype distribution among Lebanese patients with Hodgkin's lymphoma.
AB - INTRODUCTION: In addition to their important role in fighting infection, natural
killer cells are cytotoxic to cancer cells. Studies demonstrated that some KIR
genes were responsible for the reduction of the risk of Hodgkin's lymphoma (HL)
while others were associated with an increased risk of HL. AIM: The aim of this
study is to assess KIR genotypic distribution in Lebanese patients with Hodgkin's
lymphoma. METHODS: KIR genotype was analyzed in 41 HL patients and 120 healthy
Lebanese individuals using the KIR Genotyping SSP kit. RESULTS: No significant
association between HL and any KIR gene was found. Among HL patients, the AA, AB,
and BB genotype frequencies were, respectively, 41.46%, 43.9% and 14.63% with an
A:B ratio of 1.73:1. As for the controls, the AA, AB, and BB genotype frequencies
were, respectively, 39.17%, 50%, and 10.83% with an A:B ratio of 1.79:1.
CONCLUSION: In this first study from the Mediterranean region, KIR genotype does
not seem to be associated with Hodgkin's lymphoma. Further clinical and
translational research is needed to rule out the protective or predisposing role
of KIR genes in this important clinical entity.
PMID- 25853063
TI - Synthesis and Antimicrobial Activity of 6-Thioxo-6,7-dihydro-2H
[1,2,4]triazino[2,3-c]-quinazolin-2-one Derivatives.
AB - Potassium 8-R(1)-9-R(2)-10-R(3)-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6
thiolates 2.1-2.26 were synthesized via cyclocondensation of 6-R-3-(3-R(1)-4-R(2)
5-R(3)-aminophenyl)-1,2,4-triazin-5-ones 1.1-1.26 with carbon disulfide,
potassium hydroxide, and ethanol or with potassium O-ethyl dithiocarbonate in 2
propanol. The corresponding thiones 3.1-3.26 were obtained by treatment of 2.1
2.26 with hydrochloric acid. It was found that the nature of the substituents in
positions 3, 4, and 5 of the corresponding 6-R-3-(3-R(1)-4-R(2)-5-R(3)
aminophenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction. The
structures of compounds were proven by a complex of physicochemical methods
((1)H, (13)C NMR, LC-MS, and EI-MS). The results of the antibacterial and
antifungal activity assay allowed the determination of the high sensitivity of
Staphylococcus aureus ATCC 25923 (MIC 6.25-100 MUg/mL, MBC 12.5-200 MUg/mL) to
the synthesized compounds.
PMID- 25853062
TI - Selective Phosphodiesterase 4B Inhibitors: A Review.
AB - Phosphodiesterase 4B (PDE4B) is a member of the phosphodiesterase family of
proteins that plays a critical role in regulating intracellular levels of cyclic
adenosine monophosphate (cAMP) by controlling its rate of degradation. It has
been demonstrated that this isoform is involved in the orchestra of events which
includes inflammation, schizophrenia, cancers, chronic obstructive pulmonary
disease, contractility of the myocardium, and psoriatic arthritis.
Phosphodiesterase 4B has constituted an interesting target for drug development.
In recent years, a number of PDE4B inhibitors have been developed for their use
as therapeutic agents. In this review, an up-to-date status of the inhibitors
investigated for the inhibition of PDE4B has been given so that this rich source
of structural information of presently known PDE4B inhibitors could be helpful in
generating a selective and potent inhibitor of PDE4B.
PMID- 25853064
TI - Short and Efficient Synthesis of Alkyl- and Aryl-Ortho-Hydroxy-Anilides and their
Antibiotic Activity.
AB - Ortho-hydroxy-anilides are part of natural products like the new antibiotics
platencin (A) and platensimycin (B). An important step in the total synthesis of
these antibiotics or their derivatives is the preparation of the o-hydroxy
anilide partial structure. The presented method allows the preparation of o
hydroxy-anilides and o-dihydroxy-anilides from 2-nitrophenol esters in a one-step
synthesis without protecting the hydroxy group. Aryl- and alkyl-anilides were
prepared following this method as simple analogues of platensimycin (A). The
resulting compounds were tested in an agar diffusion assay for their antibiotic
potency.
PMID- 25853065
TI - Quality by Design-Based Development of a Stability-Indicating RP-HPLC Method for
the Simultaneous Determination of Methylparaben, Propylparaben, Diethylamino
Hydroxybenzoyl Hexyl Benzoate, and Octinoxate in Topical Pharmaceutical
Formulation.
AB - A stability-indicating RP-HPLC method has been developed and validated for the
simultaneous determination of methylparaben (MP), propylparaben (PP),
diethylamino hydroxybenzoyl hexyl benzoate (DAHHB), and octinoxate (OCT) in
topical pharmaceutical formulation. The desired chromatographic separation was
achieved on the Kinetex(TM) C18 (250 * 4.6 mm, 5 MUm) column using gradient
elution at 257 nm detection wavelength. The optimized mobile phase consisted of a
buffer : acetonitrile : tetrahydrofuran (60 : 30 : 10, v/v/v) as solvent A and
acetonitrile : tetrahydrofuran (70 : 30, v/v) as solvent B. The method showed
linearity over the range of 0.19-148.4 MUg/mL, 0.23-15.3 MUg/mL, 1.97-600.5
MUg/mL, and 1.85-451.5 MUg/mL for MP, PP, DAHHB, and OCT, respectively. Recovery
for all the components was found to be in the range of 98-102%. The stability
indicating capability of the developed method was established by analysing the
forced degradation samples in which the spectral purity of MP, PP, DAHHB, and
OCT, along with the separation of the degradation products from the analyte
peaks, was achieved. The proposed method was successfully applied for the
quantitative determination of MP, PP, DAHHB, and OCT in the lotion sample. The
design expert with ANOVA software with the linear model was applied and a 2(4)
full factorial design was employed to estimate the model coefficients and also to
check the robustness of the method. Results of the two-level full factorial
design, 2(4) with 20 runs including four centrepoint analysis based on the
variance analysis (ANOVA), demonstrated that all four factors, as well as the
interactions of resolution between DAHHB and OCT are statistically significant.
PMID- 25853066
TI - Validated Stability-Indicating RP-HPLC Method for the Simultaneous Determination
of Azelnidipine and Olmesartan in Their Combined Dosage Form.
AB - A simple, rapid, and highly selective RP-HPLC method was developed for the
simultaneous determination of Azelnidipine (AZL) and Olmesartan (OLM) drug
substances in the fixed dosage strength of 16 mg and 20 mg, respectively.
Effective chromatographic separation was achieved using a Hypersil GOLD C18
column (150 mm * 4.6 mm internal diameter, 5 um particle size) with a mobile
phase composed of methanol, acetonitrile, and water in the ratio of 40:40:20 (by
volume). The mobile phase was pumped using a gradient HPLC system at a flow rate
of 0.5 mL/min, and quantification of the analytes was based on measuring their
peak areas at 260 nm. The retention times for Azelnidipine and Olmesartan were
about 8.56 and 3.04 min, respectively. The reliability and analytical performance
of the proposed HPLC procedure were statistically validated with respect to
system suitability, linearity, ranges, precision, accuracy, specificity,
robustness, detection, and quantification limits. Calibration curves were linear
in the ranges of 2-48 MUg/mL for Azelnidipine and 2.5-60 MUg/mL for Olmesartan
with correlation coefficients >0.990. The proposed method proved to be selective
and stability-indicating by the resolution of the two analytes from the forced
degradation (hydrolysis, oxidation, and photolysis) products. The validated HPLC
method was successfully applied to the analysis of AZL and OLM in their combined
dosage form.
PMID- 25853067
TI - Reflections on Decisions Made on the Well-Established Use of Medicinal Products
by EU Regulators and the ECJ.
AB - BACKGROUND: In the European Union (EU), a medicinal product needs a marketing
authorization (MA) to be placed on the market. The EU's medicinal products'
legislative framework allows for a reduced application for medicines outside
their data exclusivity. One such type of application is the well-established use
(WEU) medicinal product application (i.e. bibliographic applications). Recently,
these MA applications have been subject to arbitration procedures at the European
Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) because
of disagreements between member states during the authorisation process. This
paper reflects on these cases and highlights their potential impact on future WEU
applications. METHODS: Decisions adopted by the European Commission on WEU
applications between 2009 and 2012 were identified from the EU Community Register
on medicinal products for human use. Subsequently, decisions were reviewed to
understand the potential serious risk to public health (PSRPH) that EU regulators
raised during MA application procedures. RESULTS: Four decisions were adopted by
the EU commission between 2009 and 2012. Three followed disagreements between
member states on PSRPH grounds. One decision was the outcome of a centralised
marketing authorisation application. Six key messages were identified from the
four cases reviewed and presented. CONCLUSION: A guideline on WEU to implement
the technical specifications to fulfil Annex I of Directive 2001/83/EC for MA
applications is not available. Thus, reflections on recent decisions on WEU
applications provide scientific direction to the industry as well as the
medicinal product regulators on the documentation required to successfully file
and obtain a WEU MA.
PMID- 25853068
TI - HPLC-DAD Method for the Pharmacokinetic Interaction Study of Atorvastatin with
Pioglitazone and Cholestyramine in Wistar Rats.
AB - Carotid intima-media thickness is used as a surrogate marker for cardiovascular
complications in diabetes mellitus. The combination of atorvastatin and
pioglitazone was found to be effective in reducing the thickness of the carotid
intima-media layer. The method of RP-HPLC coupled with a diode array detector
(DAD) was developed for the pharmacokinetic interaction study of atorvastatin
with pioglitazone and cholestyramine, respectively, in Wistar rats. Atorvastatin
(ATR) and pioglitazone (PIO) were resolved on a C18 column with a mobile phase
composed of 48% methanol, 19% acetonitrile, and 33% 10 mM ammonium formate
(v/v/v; pH 3.5+/-0.3, by formic acid) and a 260 nm detection wavelength on the
diode array detector. The method was validated according to international
standards with good reproducibility and linear response; mean (r) 0.9987 and
0.9972 to ATR and PIO, respectively. The coefficients of variation of intra- and
interassay precision ranged between 4.95-8.12 and 7.29-9.67, respectively.
Pharmacokinetic parameters were determined in rats following an oral
administration of atorvastatin in the presence and absence of pioglitazone and
also with cholestyramine. Compared with the control given atorvastatin alone, the
Cmax and AUC of atorvastatin were merely unchanged in rats with the co
administration of pioglitazone, while they decreased by nearly 21 and 15%,
respectively, with the concurrent use of cholestyramine. There were no
significant changes in Tmax and the plasma half-life (T1/2 ) of atorvastatin in
both cases. The performed experiment demonstrated that the presented method was
suitable for the estimation and pharmacokinetic interaction study of atorvastatin
with pioglitazone and cholestyramine in Wistar rat plasma.
PMID- 25853069
TI - Development and validation of a liquid chromatography-mass spectrometry method
for the determination of zileuton in human plasma.
AB - A selective and sensitive liquid chromatography-tandem mass spectrometric method
(LC-MS/MS) has been developed and validated for the quantification of zileuton in
human plasma. Deuterated internal standard (zileuton D4) was used as the internal
standard (ISTD). Zileuton was extracted by liquid-liquid extraction using methyl
tert-butyl ether and separated by isocratic elution on a C18 column (100 * 4.6
mm, 5 MUm, Discovery C18) with the mobile phase consisting of 1 mM ammonium
acetate buffer and methanol in the ratio of 10:90. A flow rate of 1.0 ml/min was
used with isocratic elution. Multiple reaction monitoring transitions in positive
mode for zileuton and the internal standard were 237.3/161.2 and 241.2/161.1,
respectively. The method was validated within the linearity range of 50.5
10,012.7 ng/ml for the bioanalytical method validation parameters like
selectivity, accuracy, precision, recovery, stability, and matrix effect.
PMID- 25853070
TI - Development and Validation of a LC-MS/MS Method for the Simultaneous Estimation
of Amlodipine and Valsartan in Human Plasma: Application to a Bioequivalence
Study.
AB - A reliable, simple, and robust liquid chromatography-tandem mass spectro-metric
(LC-MS/MS) method has been developed and validated that employs solid-phase
extraction for the simultaneous estimation of amlodipine and valsartan in human
K3EDTA plasma using amlodipine-d4 and valsartan-d9 as internal standards.
Chromatographic separation of amlodipine and valsartan was achieved on the Luna
C18 (2)100A (150 * 4.6 mm, 5 MUm) column using acetonitrile: 5 mM ammonium
formate solution (80:20, v/v) as the mobile phase at a flow rate of 0.8 mL/min in
isocratic mode. Quantification was achieved using an electrospray ion interface
operating in positive mode, under multiple reaction monitoring (MRM) conditions.
The assay was found to be linear over the range of 0.302-20.725 ng/mL for
amlodipine and 6.062-18060.792 ng/mL for valsartan. The method has shown good
reproducibility, as intra- and interday precisions were within 10% and accuracies
were within 8% of nominal values for both analytes. The method was successfully
applied for the bioequivalence study of amlodipine and valsartan after oral
administration of a fixed dose of the combination. Additionally, as required by
the current regulatory bodies, incurred sample reanalysis was performed and found
to be acceptable.
PMID- 25853071
TI - New Chemometrics Mode Based on Adjacent Data Points' Differences for the
Simultaneous Determination of Clopidogrel, Atorvastatin, and Aspirin in their
Combined Ternary Drug Formulation.
AB - A new method is proposed for the analysis of a ternary mixture composed of
clopidogrel, atorvastatin, and aspirin without prior separation steps. The method
combines the advantages of the mean centering of ratio spectra and derivative
spectrophotometric methods. It is based on using the difference between adjacent
data points in the absorbance spectra. The principal advantage of this method is
the use of absorbance data, and not derivative data; hence the signal-to-noise
ratio is not diminished. The mathematical explanation of the procedure is
illustrated. Beer's law was valid in the concentration range 0.3-35 MUg.mL(-1)
for CLOP, 0.5-30 MUg.mL(-1) for ATOR, and 1-40 MUg.mL(-1) for ASP. Mean
recoveries were obtained as 100.2, 100.1, and 100.2% for CLOP, ATOR, and ASP,
respectively, in the prepared synthetic mixtures. The method has been
successfully applied to the simultaneous determination of ternary mixtures of
aspirin, clopidogrel bisulphate, and atorvastatin calcium. The analytical
characteristics of the method were calculated. The results showed that the new
method is simple, rapid, accurate, and precise.
PMID- 25853072
TI - An Experimental Design Approach for Impurity Profiling of Valacyclovir-Related
Products by RP-HPLC.
AB - Impurity profiling has become an important phase of pharmaceutical research where
both spectroscopic and chromatographic methods find applications. The analytical
methodology needs to be very sensitive, specific, and precise which will separate
and determine the impurity of interest at the 0.1% level. Current research
reports a validated RP-HPLC method to detect and separate valacyclovir-related
impurities (Imp-E and Imp-G) using the Box-Behnken design approach of response
surface methodology. A gradient mobile phase (buffer: acetonitrile as mobile
phase A and acetonitrile: methanol as mobile phase B) was used. Linearity was
found in the concentration range of 50-150 MUg/mL. The mean recovery of
impurities was 99.9% and 103.2%, respectively. The %RSD for the peak areas of Imp
E and Imp-G were 0.9 and 0.1, respectively. No blank interferences at the
retention times of the impurities suggest the specificity of the method. The LOD
values were 0.0024 MUg/mL for Imp-E and 0.04 MUg/mL for Imp-G and the LOQ values
were obtained as 0.0082 MUg/mL and 0.136 MUg/mL, respectively, for the
impurities. The S/N ratios in both cases were within the specification limits.
Proper peak shapes and satisfactory resolution with good retention times
suggested the suitability of the method for impurity profiling of valacyclovir
related drug substances.
PMID- 25853073
TI - Lack of Association between the Serotonin Transporter (5-HTT) and Serotonin
Receptor (5-HT2A) Gene Polymorphisms with Smoking Behavior among Malaysian
Malays.
AB - An insertion/deletion polymorphism in the promoter region of the serotonin
transporter gene (5-HTTLPR) and a polymorphism (rs6313) in the serotonin 2A
receptor gene (5-HT2A) have previously been linked to smoking behavior. The
objective of this study was to determine the possible association of the 5-HTTLPR
and 5-HT2A gene polymorphisms with smoking behavior within a population of
Malaysian male smokers (n=248) and non-smokers (n=248). The 5-HTTLPR genotypes
were determined using the polymerase chain reaction (PCR) and were classified as
short (S) alleles or long (L) alleles. The 5HT2A genotypes were determined using
PCR-restriction fragment length polymorphisms (PCR-RFLP). No significant
differences in the distribution frequencies of the alleles were found between the
smokers and the non-smokers for the 5-HTTLPR polymorphism (x(2) = 0.72, P>0.05)
or the 5HT2A polymorphism (x(2) = 0.73, P>0.05). This is the first study
conducted on Malaysian Malay males regarding the association of 5-HTTLPR and
5HT2A polymorphisms and smoking behavior. However, the genes were not found to be
associated with smoking behavior in our population.
PMID- 25853074
TI - Evaluation of the anticonvulsant and anxiolytic potentials of methyl jasmonate in
mice.
AB - Methyl jasmonate (MJ) is one of the most well-studied plant stress hormones
belonging to the jasmonate family. Previous studies have shown that MJ
potentiated pentobarbitone sleeping time and enhanced GABA-mediated inhibitory
neurotransmission, suggesting potential benefits in disorders associated with
hyperactivity of the brain. This study was carried out to evaluate whether MJ has
anticonvulsant and anxiolytic properties in mice. The anticonvulsant effect was
assessed based on the prevention of tonic-clonic seizures induced by
chemoconvulsant agents in mice. The anxiolytic property was evaluated utilizing
the elevated plus maze (EPM) and light/dark transition paradigms. The effect of
MJ on spontaneous locomotor activity (SMA) was also assessed. Mice received
intraperitoneal (i.p.) injections of MJ 30 min before the tests were carried out
and diazepam (2 mg/kg, i.p.) was used as the reference drug. MJ (50-400 mg/kg)
did not protect the mice against tonic-clonic convulsions induced by picrotoxin
(10 mg/kg, i.p.) or strychnine (3 mg/kg, i.p.). However, MJ (100, 200, and 400
mg/kg) offered 20, 60, and 100% protection against pentylenetetrazole (100 mg/kg,
i.p.)-induced convulsions. In a similar manner to diazepam (2 mg/kg), MJ (400
mg/kg) produced a marked sedative effect as shown by decreases in the number of
lines crossed and the duration of ambulation in the open field test. In contrast
to diazepam (2 mg/kg), MJ (5-50 mg/kg) did not show anxiolytic effects in the EPM
and light/dark transition paradigms. These findings suggest that methyl jasmonate
at high doses possessed anticonvulsant properties in the pentylenetetrazole
animal model of epilepsy, but did not produce anxiolytic activity in mice.
PMID- 25853075
TI - Preparation, in vitro characterization, and in vivo pharmacokinetic evaluation of
respirable porous microparticles containing rifampicin.
AB - This study aimed to prepare and evaluate rifampicin microparticles for the lung
delivery of rifampicin as respirable powder. The microparticles were prepared
using chitosan by the spray-drying method and evaluated for aerodynamic
properties and pulmonary drug absorption. To control the drug release, tripoly
phosphate in different concentrations 0.6, 0.9, 1.2, and 1.5 was employed to get
a sustained drug release profile. The microparticles were evaluated for drug
loading, % entrapment efficiency, tapped density, morphological characteristics,
and in vitro drug release studies. Aerosol properties were determined using the
Andersen cascade impactor. Porous microparticles with particle sizes (d0.5) less
than 10 MUm were obtained. The entrapment of rifampicin in microparticles was up
to 72%. In vitro drug release suggested that the crosslinked microparticles
showed sustained release for more than 12 hrs. The drug release rate was found to
be decreased as the TPP concentration was increased. The microparticles showed a
fine particle fraction in the range of 55-63% with mass median aerodynamic
diameter (MMAD) values below 3 MUm. The in vivo pulmonary absorption of the
chitosan microparticles suggested a sustained drug release profile up to 72 hrs
with an elimination rate of 0.010 per hr. The studies revealed that the spray
dried porous microparticles have suitable properties to be used as respirable
powder in rifampicin delivery to the lungs.
PMID- 25853076
TI - Release kinetics of papaverine hydrochloride from tablets with different
excipients.
AB - The influence of excipients on the disintegration times of tablets and the
release of papaverine hydrochloride (PAP) from tablets were studied. Ten
different formulations of tablets with PAP were prepared by direct powder
compression. Different binders, disintegrants, fillers, and lubricants were used
as excipients. The release of PAP was carried out in the paddle apparatus using
0.1 N HCl as a dissolution medium. The results of the disintegration times of
tablets showed that six formulations can be classified as fast dissolving tablets
(FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3
lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC
90, magnesium stearate, and the addition of disintegrants such as AcDiSol and
Kollidon CL. Drug release kinetics were estimated by the zero- and first-order,
Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the
tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab
(44% and 60%) without the addition of a disintegrant were well-fitted to the
kinetics models such as the Higuchi and zero-order, which are suitable for
controlled- or sustained-release.
PMID- 25853077
TI - Oral Immunization Against Candidiasis Using Lactobacillus casei Displaying
Enolase 1 from Candida albicans.
AB - Candidiasis is a common fungal infection that is prevalent in immunocompromised
individuals. In this study, an oral vaccine against Candida albicans was
developed by using the molecular display approach. Enolase 1 protein (Eno1p) of
C. albicans was expressed on the Lactobacillus casei cell surface by using poly
gamma-glutamic acid synthetase complex A from Bacillus subtilis as an anchoring
protein. The Eno1p-displaying L. casei cells were used to immunize mice, which
were later challenged with a lethal dose of C. albicans. The data indicated that
the vaccine elicited a strong IgG response and increased the survival rate of the
vaccinated mice. Furthermore, L. casei acted as a potent adjuvant and induced
high antibody titers that were comparable to those induced by strong adjuvants
such as the cholera toxin. Overall, the molecular display method can be used to
rapidly develop vaccines that can be conveniently administered and require
minimal processing.
PMID- 25853078
TI - The role of magnetic resonance imaging techniques in the diagnosis, surgical
treatment and biological understanding of epilepsy.
PMID- 25853079
TI - Post-processing of structural MRI for individualized diagnostics.
AB - Currently, a relevant proportion of all histopathologically proven focal cortical
dysplasia (FCD) escape visual detection; this shows the need for additional
improvements in analyzing MRI data. A positive MRI is still the strongest
prognostic factor for postoperative freedom of seizures. Among several post
processing methods voxel-based morphometry (VBM) of T1- and T2-weighted sequences
and T2 relaxometry are routinely applied in pre-surgical diagnostics of
cryptogenic epilepsy in epilepsy centers. VBM is superior to conventional visual
analysis with 9-15% more identified epileptogenic foci, while T2 relaxometry has
its main application in (mesial) temporal lobe epilepsy. Further methods such as
surface-based morphometry (SBM) or diffusion tensor imaging are promising but
there is a lack of current studies comparing their individual diagnostic value.
Post-processing methods represent an important addition to conventional visual
analysis but need to be interpreted with expertise and experience so that they
should be apprehended as a complementary tool within the context of the multi
modal evaluation of epilepsy patients. This review will give an overview of
existing post-processing methods of structural MRI and outline their clinical
relevance in detection of epileptogenic structural changes.
PMID- 25853081
TI - Quantifying the deficit-imaging neurobehavioural impairment in childhood
epilepsy.
AB - BACKGROUND: Neurobehavioral impairments such as learning difficulty, autism,
attention deficit hyperactivity disorder (ADHD) and mood or behavioural problems
are known to be increased in children with epilepsy; however, they remain under
recognised and often cause considerable morbidity. Quantitative neuroimaging
techniques offer a potential avenue to improving our understanding of the
underlying pathological basis for these disorders, aiding with diagnosis and risk
stratification. METHODS: A systematic review was undertaken for original research
articles involving magnetic resonance imaging in children with epilepsy and one
or more neurobehavioural impairments. Studies were reviewed with respect to
patient population, methodology and magnetic resonance imaging (MRI) findings.
RESULTS: A total of 25 studies were identified and included in this review. The
majority of studies looked at single impairments, commonly cognitive impairment
or ADHD, with few studies reporting on other impairments. Reductions in cortical
grey matter and disruptions of functional and structural brain networks were
associated with poorer cognitive performance and disruptions of grey and white
matter within a fronto-striatal-cerebellar network associated with ADHD.
Insufficient studies were available to report on other impairments. CONCLUSIONS:
Relatively few studies exist in this field and those that do are methodologically
diverse. Further investigation is required to determine if the changes reported
to date are epilepsy syndrome specific or have broader applicability.
PMID- 25853082
TI - The effects of antiepileptic drugs on cognitive functional magnetic resonance
imaging.
AB - The cognitive dysfunction caused by antiepileptic drugs (AEDs) has been
extensively described, although the mechanisms underlying such collateral effects
are still poorly understood. The combination of functional magnetic resonance
imaging (fMRI) studies with pharmacological intervention (pharmaco-MRI or ph-MRI)
offers the opportunity to investigate the effect of drugs such as AEDs on brain
activity, including cognitive tasks. Here we review the studies that investigated
the effects of AEDs [topiramate (TPM), lamotrigine (LMT), carbamazepine (CBZ),
pregabalin (PGB), valproate (VPA) and levetiracetam (LEV)] on cognitive fMRI
tasks. Despite the scarcity of fMRI studies focusing on the impact of AEDs on
cognitive task, the results of recent work have provided important information
about specific drug-related changes of brain function.
PMID- 25853080
TI - Quantitative MRI in refractory temporal lobe epilepsy: relationship with surgical
outcomes.
AB - Medically intractable temporal lobe epilepsy (TLE) remains a serious health
problem. Across treatment centers, up to 40% of patients with TLE will continue
to experience persistent postoperative seizures at 2-year follow-up. It is
unknown why such a large number of patients continue to experience seizures
despite being suitable candidates for resective surgery. Preoperative
quantitative MRI techniques may provide useful information on why some patients
continue to experience disabling seizures, and may have the potential to develop
prognostic markers of surgical outcome. In this article, we provide an overview
of how quantitative MRI morphometric and diffusion tensor imaging (DTI) data have
improved the understanding of brain structural alterations in patients with
refractory TLE. We subsequently review the studies that have applied quantitative
structural imaging techniques to identify the neuroanatomical factors that are
most strongly related to a poor postoperative prognosis. In summary, quantitative
imaging studies strongly suggest that TLE is a disorder affecting a network of
neurobiological systems, characterized by multiple and inter-related limbic and
extra-limbic network abnormalities. The relationship between brain alterations
and postoperative outcome are less consistent, but there is emerging evidence
suggesting that seizures are less likely to remit with surgery when presurgical
abnormalities are observed in the connectivity supporting brain regions serving
as network nodes located outside the resected temporal lobe. Future work,
possibly harnessing the potential from multimodal imaging approaches, may further
elucidate the etiology of persistent postoperative seizures in patients with
refractory TLE. Furthermore, quantitative imaging techniques may be explored to
provide individualized measures of postoperative seizure freedom outcome.
PMID- 25853083
TI - What does diffusion tensor imaging (DTI) tell us about cognitive networks in
temporal lobe epilepsy?
AB - Diffusion tensor imaging (DTI) has provided considerable insight into our
understanding of epilepsy as a network disorder, revealing subtle alterations in
white matter microstructure both proximal and distal to the epileptic focus.
These white matter changes have been shown to assist with lateralizing the
seizure focus, as well as delineating the location/anatomy of key white matter
tracts (i.e., optic radiations) for surgical planning. However, only recently
have studies emerged describing the utility of DTI for probing cognitive networks
in patients with epilepsy and for examining the structural plasticity within
these networks both before and after epilepsy surgery. Here, we review the
current literature describing the use of DTI for understanding language and
memory networks in patients with temporal lobe epilepsy (TLE), as well as the
extant literature on networks associated with executive functioning and global
intelligence. Studies of memory and language reveal a complex network of
frontotemporal fibers that contribute to naming and fluency performance in TLE,
and demonstrate that these networks appear to undergo adaptive changes in
response to surgical intervention. Although studies of executive functioning and
global intelligence have been less conclusive, there is accumulating evidence
that aberrant communication between frontoparietal and medial temporal networks
may underlie working memory impairment in TLE. More recently, multimodal imaging
studies have provided evidence that disruptions within these white matter
networks co-localize with functional changes observed on functional MRI. However,
structure-function associations are not entirely coherent and may breakdown in
patients with TLE, especially those with a left-sided seizure focus. Although the
reasons for discordant findings are unclear, small sample sizes, heterogeneity
within patient populations and limitations of the current tensor model may
account for contradictory and null findings. Improvements in imaging hardware and
higher field strengths have now paved the way for the implementation of advanced
diffusion techniques, and these advanced models show great promise for improving
our understanding of how network dysfunction contributes to cognitive morbidity
in TLE.
PMID- 25853085
TI - The potential role of novel diffusion imaging techniques in the understanding and
treatment of epilepsy.
AB - Epilepsy is a common neurological disorder in which magnetic resonance imaging
plays a key role. Diffusion imaging based on the molecular diffusion of water has
been widely used clinically and in research for patients with epilepsy. Diffusion
tensor imaging (DTI), the most common model, has been used for around two
decades. Several parameters can be derived from DTI that are sensitive, but non
specific, to underlying structural changes. DTI assumes a single diffusion
process following a Gaussian distribution within each voxel and is thus an overly
simplistic representation of tissue microstructure. Several more advanced models
of diffusion are now available that may have greater utility in the understanding
of the effects of epilepsy on tissue microstructure. In this review, I summarise
the principles, applications in epilepsy and future potential of three such
techniques. Diffusion kurtosis imaging (DKI) characterises the degree to which
diffusion deviates from Gaussian behaviour and gives an idea of the underlying
tissue complexity. It has been used in both focal and generalised epilepsy and
seems more sensitive than DTI. Multi-compartment models separate the signal from
extra- and intra-axonal compartments in each voxel. The Composite Hindered and
Restricted Model of Diffusion (CHARMED) can characterise axonal density but has
not yet been applied in patients with epilepsy. The Neurite Orientation
Dispersion and Density Imaging (NODDI) model can determine the intracellular
volume fraction (ICVF) and degree of dispersion of neurite orientation.
Preliminary data suggest it may more sensitive than conventional and diffusion
imaging in localising focal epilepsy.
PMID- 25853086
TI - Strengths and limitations of tractography methods to identify the optic radiation
for epilepsy surgery.
AB - Diffusion tensor imaging (DTI) tractography (TG) can visualize Meyer's loop (ML),
providing important information for the epilepsy surgery team, both for
preoperative counseling and to reduce the frequency of visual field defects after
temporal lobe resection (TLR). This review highlights significant steps in the TG
process, specifically the processing of raw data including choice of TG algorithm
and the interpretation and validation of results. A lack of standardization of TG
of the optic radiation makes study comparisons challenging. We discuss results
showing differences between studies and uncertainties large enough to be of
clinical relevance and present implications of this technique for temporal lobe
epilepsy surgery. Recent studies in temporal lobe epilepsy patients, employing TG
intraoperatively, show promising results in reduction of visual field defects,
with maintained seizure reduction.
PMID- 25853084
TI - White matter in temporal lobe epilepsy: clinico-pathological correlates of water
diffusion abnormalities.
AB - Using magnetic resonance imaging, it is possible to measure the behavior of
diffusing water molecules, and the metrics derived can be used as indirect
markers of tissue micro-architectural properties. Numerous reports have
demonstrated that patients with temporal lobe epilepsy (TLE) have water diffusion
abnormalities in several white matter structures located within and beyond the
epileptogenic temporal lobe, showing that TLE is not a focal disorder, but rather
a brain network disease. Differences in severity and spatial extent between
patients with or without mesial temporal sclerosis (MTS), as well as differences
related to hemispheric seizure onset, are suggestive of different
pathophysiological mechanisms behind different forms of TLE, which in turn result
in specific cognitive disabilities. The biological interpretation of diffusion
abnormalities is based on a wealth of information from animal models of white
matter damage, and is supported by recent reports that directly correlate
diffusion metrics with histological characteristics of surgical specimens of TLE
patients. Thus, there is now more evidence showing that the increased mean
diffusivity (MD) and concomitant reductions of diffusion anisotropy that are
frequently observed in several white matter bundles in TLE patients reflect
reduced axonal density (increased extra-axonal space) due to smaller-caliber
axons, and abnormalities in the myelin sheaths of the remaining axons. Whether
these histological and diffusion features are a predisposing factor for epilepsy
or secondary to seizures is still uncertain; some reports suggest the latter.
This article summarizes recent findings in this field and provides a synopsis of
the histological features seen most frequently in post-surgical specimens of TLE
patients in an effort to aid the interpretation of white matter diffusion
abnormalities.
PMID- 25853089
TI - Modeling cytomegalovirus infection in mouse tumor models.
AB - The hypothesis that cytomegalovirus (CMV) modulates cancer is evolving.
Originally discovered in glioblastoma in 2002, the number of cancers, where
intratumoral CMV antigen is detected, has increased in recent years suggesting
that CMV actively affects the pathobiology of certain tumors. These findings are
controversial as several groups have also reported inability to replicate these
results. Regardless, several clinical trials for glioblastoma are underway or
have been completed that target intratumoral CMV with anti-viral drugs or
immunotherapy. Therefore, a better understanding of the possible pathobiology of
CMV in cancer needs to be ascertained. We have developed genetic, syngeneic, and
orthotopic malignant glioma mouse models to study the role of CMV in cancer
development and progression. These models recapitulate for the most part
intratumoral CMV expression as seen in human tumors. Additionally, we discovered
that CMV infection in Trp53(-/+) mice promotes pleomorphic rhabdomyosarcomas.
These mouse models are not only a vehicle for studying pathobiology of the viral
tumor interaction but also a platform for developing and testing cancer
therapeutics.
PMID- 25853087
TI - Methods and utility of EEG-fMRI in epilepsy.
AB - Brain activity data in general and more specifically in epilepsy can be
represented as a matrix that includes measures of electrophysiology, anatomy and
behaviour. Each of these sub-matrices has a complex interaction depending upon
the brain state i.e., rest, cognition, seizures and interictal periods. This
interaction presents significant challenges for interpretation but also potential
for developing further insights into individual event types. Successful
treatments in epilepsy hinge on unravelling these complexities, and also on the
sensitivity and specificity of methods that characterize the nature and
localization of underlying physiological and pathological networks. Limitations
of pharmacological and surgical treatments call for refinement and elaboration of
methods to improve our capability to localise the generators of seizure activity
and our understanding of the neurobiology of epilepsy. Simultaneous
electroencephalography and functional magnetic resonance imaging (EEG-fMRI), by
potentially circumventing some of the limitations of EEG in terms of sensitivity,
can allow the mapping of haemodynamic networks over the entire brain related to
specific spontaneous and triggered epileptic events in humans, and thereby
provide new localising information. In this work we review the published
literature, and discuss the methods and utility of EEG-fMRI in localising the
generators of epileptic activity. We draw on our experience and that of other
groups, to summarise the spectrum of information provided by an increasing number
of EEG-fMRI case-series, case studies and group studies in patients with
epilepsy, for its potential role to elucidate epileptic generators and networks.
We conclude that EEG-fMRI provides a multidimensional view that contributes
valuable clinical information to localize the epileptic focus with potential
important implications for the surgical treatment of some patients with drug
resistant epilepsy, and insights into the resting state and cognitive network
dynamics.
PMID- 25853088
TI - Utility of magnetic resonance spectroscopic imaging for human epilepsy.
AB - This review discusses the potential utility of broad based use of magnetic
resonance (MR) spectroscopic imaging for human epilepsy and seizure localization.
The clinical challenges are well known to the epilepsy community, intrinsic in
the variability of location, volumetric size and network extent of epileptogenic
tissue in individual patients. The technical challenges are also evident, with
high performance requirements in multiple steps, including magnet homogeneity,
detector performance, sequence design, speed of acquisition in addition to large
territory spectral processing. We consider how MR spectroscopy and spectroscopic
imaging has been informative for epilepsy thus far, with specific attention to
what is measured, the interpretation of such measurements and technical
performance challenges. Examples are shown from medial temporal lobe and
neocortical epilepsies are considered from 4T, 7T and most recently 3T.
PMID- 25853090
TI - Hereditary cancer risk assessment: challenges for the next-gen sequencing era.
PMID- 25853091
TI - Cancer-associated fibroblasts connect metastasis-promoting communication in
colorectal cancer.
AB - Colorectal cancer (CRC) progression and eventually metastasis is directed in many
aspects by a circuitous ecosystem consisting of an extracellular matrix scaffold
populated by cancer-associated fibroblasts (CAFs), endothelial cells, and diverse
immune cells. CAFs are recruited from local tissue-resident fibroblasts or
pericryptal fibroblasts and distant fibroblast precursors. CAFs are highly
abundant in CRC. In this review, we apply the metastasis-promoting communication
of colorectal CAFs to 10 cancer hallmarks described by Hanahan and Weinberg. CAFs
influence innate and adaptive tumor immune responses. Using datasets from
previously published work, we re-explore the potential messages implicated in
this process. Fibroblasts present in metastasis (metastasis-associated
fibroblasts) from CRC may have other characteristics and functional roles than
CAFs in the primary tumor. Since CAFs connect metastasis-promoting communication,
CAF markers are potential prognostic biomarkers. CAFs and their products are
possible targets for novel therapeutic strategies.
PMID- 25853092
TI - Image-guided radiotherapy and -brachytherapy for cervical cancer.
AB - Conventional radiotherapy for cervical cancer relies on clinical examination, 3
dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary
brachytherapy. Excellent local control and survival have been obtained for small
early stage cervical cancer with definitive radiotherapy. For bulky and locally
advanced disease, the addition of chemotherapy has improved the prognosis but
toxicity remains significant. New imaging technology such as positron-emission
tomography and magnetic resonance imaging has improved tumor delineation for
radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment
toxicity of whole pelvic radiation because of its potential for bone marrow,
bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may
optimize image-guided brachytherapy (IGBT), allowing for better local control and
reduced toxicity for patients with cervical cancer. IGRT and IGBT should be
integrated in future prospective studies for cervical cancer.
PMID- 25853093
TI - Stereotactic ablative radiosurgery for locally advanced or recurrent skull base
malignancies with prior external beam radiation therapy.
AB - PURPOSE: Stereotactic ablative radiotherapy (SABR) is an attractive modality to
treat malignancies invading the skull base as it can deliver a highly conformal
dose with minimal toxicity. However, variation exists in the prescribed dose and
fractionation. The purpose of our study is to examine the local control,
survival, and toxicities in SABR for the treatment of previously irradiated
malignant skull base tumors. MATERIALS AND METHODS: A total of 31 patients and 40
locally advanced or recurrent head and neck malignancies involving the skull base
treated with a common SABR regimen, which delivers a radiation dose of 44 Gy in 5
fractions from January 1st, 2004 to December 31st, 2013, were retrospectively
reviewed. The local control rate (LC), progression-free survival rate, overall
survival (OS) rate, and toxicities were reported. RESULTS: The median follow-up
time of all patients was 11.4 months (range: 0.6-67.2 months). The median tumor
volume was 27 cm(3) (range: 2.4-205 cm(3)). All patients received prior external
beam radiation therapy with a median radiation dose of 64 Gy (range: 24-75.6 Gy)
delivered in 12-42 fractions. Twenty patients had surgeries prior to SABR.
Nineteen patients received chemotherapy. Specifically, eight patients received
concurrent cetuximab (ErbituxTM) with SABR. The median time-to-progression (TTP)
was 3.3 months (range: 0-16.9 months). For the 29 patients (93.5%) who died, the
median time from the end of first SABR to death was 10.3 months (range: 0.5-41.4
months). The estimated 1-year OS rate was 35%. The estimated 2-year OS rate was
12%. Treatment was well-tolerated without grade 4 or 5 treatment-related
toxicities. CONCLUSION: Stereotactic ablative radiotherapy has been shown to
achieve low toxicities in locally advanced or recurrent, previously irradiated
head and neck malignancies invading the skull base.
PMID- 25853094
TI - Cardiovascular toxicities of breast cancer treatment: emerging issues in cardio
oncology.
PMID- 25853095
TI - Correlation of hemorrhage, axonal damage, and blood-tissue barrier disruption in
brain and retina of Malawian children with fatal cerebral malaria.
AB - BACKGROUND: The retinal and brain histopathological findings in children who died
from cerebral malaria (CM) have been recently described. Similar changes occur in
both structures, but the findings have not been directly compared in the same
patients. In this study, we compared clinical retinal findings and retinal and
cerebral histopathological changes in a series of patients in Blantyre, Malawi,
who died of CM. METHODS: The features systematically compared in the same patient
were: (1) clinical, gross and microscopic retinal hemorrhages with microscopic
cerebral hemorrhages, (2) retinal and cerebral hemorrhage-associated and
unassociated axonal damage, and fibrinogen leakage, and (3) differences in the
above features between the pathological categories of CM without microvascular
pathology (CM1) and CM with microvascular pathology (CM2) in retina and brain.
RESULTS: Forty-seven patients were included: seven CM1, 28 CM2, and 12 controls.
In the 35 malaria cases retinal and cerebral pathology correlated in all features
except for non-hemorrhage associated fibrinogen leakage. Regarding CM1 and CM2
cases, the only differences were in the proportion of patients with hemorrhage
associated cerebral pathology, and this was expected, based on the definitions of
CM1 and CM2. The retina did not show this difference. Non-hemorrhage associated
pathology was similar for the two groups. COMMENT: As postulated,
histopathological features of hemorrhages, axonal damage and non-hemorrhage
associated fibrinogen leakage correlated in the retina and brain of individual
patients, although the difference in hemorrhages between the CM1 and CM2 groups
was not consistently observed in the retina. These results help to underpin the
utility of ophthalmoscopic examination and fundus findings to help in diagnosis
and assessment of cerebral malaria patients, but may not help in distinguishing
between CM1 and CM2 patients during life.
PMID- 25853097
TI - Correction.
AB - [This corrects the article DOI: 10.7860/JCDR/2014/9827.5191.].
PMID- 25853098
TI - Primary cancer prevention by green tea, and tertiary cancer prevention by the
combination of green tea catechins and anticancer compounds.
AB - Green tea is a daily beverage, a non-oxidized non-fermented product containing at
least four green tea catechins. Considering our first results when repeated
applications of (-)-epigallocatechin gallate (EGCG) prevented tumor promotion in
mouse skin, we have continued to look at green tea as a possible cancer
preventive agent. 1) The 10-year prospective cohort study by Drs. K. Nakachi and
K. Imai revealed that drinking 10 Japanese-size cups (120 mL/cup) of green tea
per day delayed cancer onset in humans by 7.3 years among females and by 3.2
years among males. The delay of cancer onset is of course significant evidence of
primary cancer prevention in humans. 2) In collaboration with Dr. H. Moriwaki's
group we successfully presented a prototype of tertiary cancer prevention showing
that 10 Japanese-size cups of green tea daily, supplemented with tablets of green
tea extract (G.T.E), reduced recurrence of colorectal adenomas in polypectomy
patients by 51.6% (from 31% to 15%). 3) In 1999, we first reported that the
combination of green tea catechins and non-steroidal anti-inflammatory drugs
showed synergistic anticancer effects in both in vitro and in vivo experiments,
along with elucidation of the mechanism. 4) Further studies by other
investigators have revealed that various combinations of EGCG or green tea
extract and anticancer compounds inhibit tumor volume in xenograft mouse models
implanted with various human cancer cell lines. Green tea is a cancer preventive,
and green tea catechins act as synergists with anticancer compounds.
PMID- 25853096
TI - Approaches to treatment of emerging Shiga toxin-producing Escherichia coli
infections highlighting the O104:H4 serotype.
AB - Shiga toxin-producing Escherichia coli (STEC) are a group of diarrheagenic
bacteria associated with foodborne outbreaks. Infection with these agents may
result in grave sequelae that include fatality. A large number of STEC serotypes
has been identified to date. E. coli serotype O104:H4 is an emerging pathogen
responsible for a 2011 outbreak in Europe that resulted in over 4000 infections
and 50 deaths. STEC pathogenicity is highly reliant on the production of one or
more Shiga toxins that can inhibit protein synthesis in host cells resulting in a
cytotoxicity that may affect various organ systems. Antimicrobials are usually
avoided in the treatment of STEC infections since they are believed to induce
bacterial cell lysis and the release of stored toxins. Some antimicrobials have
also been reported to enhance toxin synthesis and production from these
organisms. Various groups have attempted alternative treatment approaches
including the administration of toxin-directed antibodies, toxin-adsorbing
polymers, probiotic agents and natural remedies. The utility of antibiotics in
treating STEC infections has also been reconsidered in recent years with certain
modalities showing promise.
PMID- 25853099
TI - Small Molecule Inhibitors to Disrupt Protein-protein Interactions of Heat Shock
Protein 90 Chaperone Machinery.
AB - Heat shock protein 90 (Hsp90) is an adenosine triphosphate dependent molecular
chaperone in eukaryotic cells that regulates the activation and maintenance of
numerous regulatory and signaling proteins including epidermal growth factor
receptor, human epidermal growth factor receptor 2, mesenchymal-epithelial
transition factor, cyclin-dependent kinase-4, protein kinase B, hypoxia-inducible
factor 1alpha, and matrix metalloproteinase-2. Since many of Hsp90 clients are
oncogenic proteins, Hsp90 has become an attractive therapeutic target for
treatment of cancer. To discover small molecule inhibitors targeting Hsp90
chaperone machinery, several strategies have been employed, which results in
three classes of inhibitors such as N-terminal inhibitors, C-terminal inhibitors,
and inhibitors disrupting protein-protein interactions of Hsp90 chaperone
machinery. Developing small molecule inhibitors that modulate protein-protein
interactions of Hsp90 is a challenging task, although it offers many alternative
opportunities for therapeutic intervention. The lack of well-defined binding
pocket and starting points for drug design challenges medicinal chemists to
discover small molecule inhibitors disrupting protein-protein interactions of
Hsp90. The present review will focus on the current studies on small molecule
inhibitors disrupting protein-protein interactions of Hsp90 chaperone machinery,
provide biological background on the structure, function and mechanism of Hsp90's
protein-protein interactions, and discuss the challenges and promise of its small
molecule modulations.
PMID- 25853100
TI - Endocrine-disrupting Chemicals: Review of Toxicological Mechanisms Using
Molecular Pathway Analysis.
AB - Endocrine disruptors are known to cause harmful effects to human through various
exposure routes. These chemicals mainly appear to interfere with the endocrine or
hormone systems. As importantly, numerous studies have demonstrated that the
accumulation of endocrine disruptors can induce fatal disorders including obesity
and cancer. Using diverse biological tools, the potential molecular mechanisms
related with these diseases by exposure of endocrine disruptors. Recently,
pathway analysis, a bioinformatics tool, is being widely used to predict the
potential mechanism or biological network of certain chemicals. In this review,
we initially summarize the major molecular mechanisms involved in the induction
of the above mentioned diseases by endocrine disruptors. Additionally, we provide
the potential markers and signaling mechanisms discovered via pathway analysis
under exposure to representative endocrine disruptors, bisphenol,
diethylhexylphthalate, and nonylphenol. The review emphasizes the importance of
pathway analysis using bioinformatics to finding the specific mechanisms of toxic
chemicals, including endocrine disruptors.
PMID- 25853102
TI - Carnosic Acid Inhibits Lipid Accumulation in 3T3-L1 Adipocytes Through
Attenuation of Fatty Acid Desaturation.
AB - BACKGROUND: Excess body fat accumulation contributes to the development of
metabolic disorders that can cause adverse health effects. Carnosic acid (CA), a
major bioactive component of rosemary (Rosemarinus officinalis), has been
suggested to possess anti-adipogenic properties. The present study was conducted
to elucidate the mechanism underlying the anti-adipogenic effects of CA. METHODS:
3T3-L1 pre-adipocytes were treated with CA (0.1, 1, and 10 MUM) from day 0 to day
8 of differentiation. On day 8, biochemical markers of lipid accumulation and the
degree of fatty acid desaturation were measured. RESULTS: Oil Red O staining
results, triglyceride (TG) accumulation, and glycerol 3-phosphate dehydrogenase
activity suggested that CA significantly inhibited lipid accumulation in 3T3-L1
adipocytes. CA significantly decreased mRNA expression of peroxisome proliferator
activated receptor-gamma, sterol regulatory element-binding protein 1, and
CCAAT/enhancer binding protein-alpha in a dose-dependent manner. Moreover, it
decreased the ratio of both C16:1/C16:0 and C18:1/C18:0, with reduced expression
of stearoyl CoA desaturase 1 mRNA and protein. CONCLUSIONS: These results suggest
that CA efficiently suppressed adipogenesis in 3T3-L1 adipocytes and its action,
at least in part, is associated with the downregulation of adipogenesis-related
genes and the fatty acid composition of TG accumulated in adipocytes.
PMID- 25853101
TI - Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion
of gastric cancer.
AB - Atrophic gastritis (AG) and intestinal metaplasia (IM) are the main precursor
lesions of gastric cancer as the incidence of gastric cancer increases in the
gastric mucosa involved with AG and IM. The prevalence of AG and IM vary
depending on countries, even it represents diverse results in the same nation.
Usually AG is antecedent of IM but the etiologies of AG and IM are not always the
same. The sensitivity and specificity of diagnostic methods to detect AG and IM
are different. Furthermore, the management strategy of AG and IM has not been
established, yet. Helicobacter pylori infection has been proved as the most
important cause of AG and IM. Thus the eradication of H. pylori is very important
to prevent the progression to gastric cancer which is still placed in the high
rank in morbidity and mortality among cancers. However, the reversibility of AG
and IM by eradication of H. pylori which was assumed to be certain by meta
analysis is; however, controversial now. Therefore, the understanding and early
diagnosis of AG and IM are very important, especially, in high incidence area of
gastric cancer such as Republic of Korea.
PMID- 25853103
TI - Anthocyanins From the Fruit of Vitis coignetiae Pulliat Potentiate the Cisplatin
Activity by Inhibiting PI3K/Akt Signaling Pathways in Human Gastric Cancer Cells.
AB - BACKGROUND: Cisplatin (cis-diaminedichloroplatinum, CDDP) is a widely used
chemotherapeutic agent for the treatment of many cancers. However, initial
resistance to CDDP is a serious problem in treating these cancers. Vitis
coignetiae Pulliat (Meoru in Korea) have shown anti-nuclear factor kappa B and
anti-epidermal growth factor receptor activities in cancer cells. METHODS: In
this study, in order to seeking an approach to increase the anti-cancer effects
of CDDP with natural products. Here, we investigated anthocyanins isolated from
Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) can enhance
anti-cancer effects of cisplatin (CDDP) in stomach cancer cells. The cell
viability of SNU-1 and SNU-16 cells after treated with AIMs and CDDP were
analyzed by MTT assay. The expressions of Akt and X-linked inhibitor of apoptosis
protein (XIAP) proteins were examined by western blot in AIMs- and CDDP-treated
cells. RESULTS: We found that AIMs enhanced anticancer effects of CDDP, which
activity was additive but not synergistic. AIMs suppressed Akt activity of the
cancer cells activated by CDDP. AIMs also suppressed in XIAP an anti-apoptotic
protein. CONCLUSIONS: This study suggests that the anthocyanins isolated from
fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by
inhibiting Akt activity activated by CDDP.
PMID- 25853104
TI - Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Growth of Gefitinib
resistant Non-small Cell Lung Cancer Cells by Inducing Apoptosis.
AB - BACKGROUND: Therapeutic approach by treatment with epidermal growth factor
receptor-tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib or erlotinib to
non-small cell lung cancer (NSCLC) patients has been limited due to emergence of
acquired drug resistance. Our study was aimed to investigate whether the
inhibition of ubiquitin-specific peptidase 8 (USP8) could be an alternative
strategy capable of overcoming acquired resistance to EGFR-TKIs for treatment of
NSCLCs. METHODS: The anticancer effect of USP8 inhibitor was determined by
testing anchorage-dependent or independent growth of gefitinib-sensitive or
resistant NSCLCs. The immunoprecipitation and western blotting were conducted to
check molecular interaction and signaling pathway followed by USP8 inhibition.
RESULTS: Inhibition of USP8 induced overall degradation of oncogenic receptor
tyrosine kinases including EGFR and Met, leading to a suppression of anchorage
dependent or independent cell growth of gefitinib-sensitive or resistant NSCLCs.
Also, treatment with the USP8 inhibitor markedly induced apoptosis in HCC827GR
cells. Notably, treatment with the USP8 inhibitor was more effective in
suppressing cell growth and inducing apoptosis in gefitinib-resistant HCC827GR
cells than that of gefitinib-sensitive HCC827 cells. CONCLUSIONS: Inhibition of
USP8 could be an effective strategy for overcoming gefitinib resistance in
NSCLCs.
PMID- 25853105
TI - A Controlled, Randomized, Double-blind Trial to Evaluate the Effect of Vegetables
and Whole Grain Powder That Is Rich in Dietary Fibers on Bowel Functions and
Defecation in Constipated Young Adults.
AB - BACKGROUND: This study evaluated the effect of vege-powder (VP), mainly consisted
of chicory, broccoli, and whole grains, on bowel habit improvement and
constipation alleviation. METHODS: Using the Roman standard II, 96 male and
female subjects in their twenties with constipation symptoms were divided into a
control group or VP group. Subjects in a control group were supplied with rice
flakes-powder (RFP) and subjects in the VP group were provided with 30 g of VP
twice daily for 4 weeks. Constipation relief effectiveness was surveyed on 5
point Likert scales depending on stool hardness, amount of stool, sensation of
incomplete evacuation, and straining to defecate at day 0, 14, and 28 of RFP or
VP intake. RESULTS: Repeated measures analysis of variance analysis revealed that
VP intake caused significant temporal changes in stool hardness, amount,
sensation of incomplete evacuation, and straining to defecate. In addition,
significant differences between control and VP groups were found in stool
hardness, amount, sensation of incomplete evacuation, and straining to defecate
at day 14 and 28 of experimental diet consumption. VP supplement for 2 weeks
significantly increased the evacuation frequency (1.04 +/- 0.71), compared to
control group (0.41 +/- 0.64) and this increase was maintained at 4 week of diet
supplements. CONCLUSIONS: This result showed that constipated subjects who
consumed VP, mainly consisting of chicory, broccoli, and whole grains, improved
constipation symptoms at 2 and 4 weeks of consumption compared to those of
control group who were provided with RFP.
PMID- 25853106
TI - Clinical Implication of p16, Ki-67, and Proliferating Cell Nuclear Antigen
Expression in Cervical Neoplasia: Improvement of Diagnostic Accuracy for High
grade Squamous Intraepithelial Lesion and Prediction of Resection Margin
Involvement on Conization Specimen.
AB - BACKGROUND: Cervical intraepithelial neoplasia (CIN) grading is subjective and
affected by substantial rates of discordance among pathologists. Although the use
of p16INK4a (p16) staining has been proven to improve diagnostic accuracy for
high-grade squamous intraepithelial lesion (HSIL), the clinical evidence for use
of Ki-67 and proliferating cell nuclear antigen (PCNA) is insufficient to make an
independent recommendation for use, alone or in combination. The primary
objective was to evaluate clinical utility of Ki-67 and PCNA in combination with
p16 in diagnosing HSIL. Also, we assessed the correlation between expressions of
three biomarkers and resection margin status of conization specimen. METHODS: The
expressions of p16, Ki-67, and PCNA were evaluated by immunohistochemical methods
in 149 cervical tissues encompassing 17 negative lesion, 31 CIN 1, 25 CIN 2, 41
CIN 3, and 35 invasive squamous cell carcinoma. The immunohistochemical staining
results were classified into four grades: 0, 1+, 2+ and 3+. RESULTS: The
expression of three biomarkers was positively associated with CIN grade. Ki-67
immunostaining did not increase the accuracy of HSIL diagnosis when combined with
p16 immunostaining compared with p16 immunostaining alone. In contrast, combining
the staining results for p16 and PCNA (p16 = 3+ and PCNA >=2+) increased its
specificity (66.7% vs. 75.0%, P = 0.031) without decrease of its sensitivity
(98.7% vs. 98.7%) for diagnosis of CIN 3 and more sever lesion. Subgroup analysis
for conization specimen with CIN 2 and CIN 3 showed that positive Ki-67
immunostaining was an independent risk factor for predicting resection margin
positivity (odds ratio = 6.52, 95% confidence interval 1.07-39.64). CONCLUSIONS:
We found that the combined use of p16 and PCNA immunostaining enhanced diagnostic
accuracy for HSIL. Positive Ki-67 immunostaining was associated with incomplete
excision.
PMID- 25853107
TI - Identification of a new selective chemical inhibitor of mutant isocitrate
dehydrogenase-1.
AB - BACKGROUND: Recent genome-wide sequencing studies have identified unexpected
genetic alterations in cancer. In particular, missense mutations in isocitrate
dehydrogenase-1 (IDH1) at arginine 132, mostly substituted into histidine (IDH1
R132H) were observed to frequently occur in glioma patients. METHODS: We have
purified recombinant IDH1 and IDH1-R132H proteins and monitored their catalytic
activities. In parallel experiments, we have attempted to find new selective IDH1
R132H chemical inhibitor(s) from a fragment-based chemical library. RESULTS: We
have found that IDH1, but not IDH1-R132H, can catalyze the conversion of
isocitrate into alpha-ketoglutarate (alpha-KG). In addition, we have observed
that IDH1-R132H was more efficient than IDH1 in converting alpha-KG into (R)-2
hydroxyglutarate (R-2HG). Moreover, we have identified a new hit molecule, e.g.,
2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one as a new selective IDH1-R132H
inhibitor. CONCLUSIONS: We have observed an underlying biochemical mechanism
explaining how a heterozygous IDH1 mutation contributes to the generation of R
2HG and increases cellular histone H3 trimethylation levels. We have also
identified a novel selective IDH1-R132H chemical hit molecule, e.g., 2-(3
trifluoromethylphenyl)isothioazol-3(2H)-one, which could be used for a future
lead development against IDH1-R132H.
PMID- 25853108
TI - Do the Benefits of Male Circumcision Outweigh the Risks? A Critique of the
Proposed CDC Guidelines.
AB - The Centers for Disease Control and Prevention (CDC) have announced a set of
provisional guidelines concerning male circumcision, in which they suggest that
the benefits of the surgery outweigh the risks. I offer a critique of the CDC
position. Among other concerns, I suggest that the CDC relies more heavily than
is warranted on studies from Sub-Saharan Africa that neither translate well to
North American populations nor to circumcisions performed before an age of sexual
debut; that it employs an inadequate conception of risk in its benefit vs. risk
analysis; that it fails to consider the anatomy and functions of the penile
prepuce (i.e., the part of the penis that is removed by circumcision); that it
underestimates the adverse consequences associated with circumcision by focusing
on short-term surgical complications rather than long-term harms; that it
portrays both the risks and benefits of circumcision in a misleading manner,
thereby undermining the possibility of obtaining informed consent; that it
evinces a superficial and selective analysis of the literature on sexual outcomes
associated with circumcision; and that it gives less attention than is desirable
to ethical issues surrounding autonomy and bodily integrity. I conclude that
circumcision before an age of consent is not an appropriate health-promotion
strategy.
PMID- 25853109
TI - Atresia of the aortic arch in 4-year-old child: a clinical case study.
AB - Atresia of the aortic arch is a rare congenital heart defect with a high
mortality when associated with other intracardiac defects. Cardiac magnetic
resonance (CMR) provides the exact anatomy of the aortic arch and collateral
circulation and is useful to diagnose-associated aortic arch anomalies. This
report describes the case of a 4-year-old child with atresia of the aortic arch,
referred to our institution with the diagnosis of aortic coarctation and bicuspid
aortic valve. On clinical exam, the femoral pulses were not palpable and there
was a significant differential blood pressure between the upper and lower limbs.
The echocardiography showed a severely stenotic bicuspid aortic valve but was
limited for the exact description of the aortic arch. CMR showed absence of lumen
continuity between the ascending and descending aorta distal to the left
subclavian artery, extending over 5 mm, with the presence of a bend in the arch
and diverticulum on either side of the zone of discontinuity, suggesting the
diagnosis atresia of the aortic arch rather than coarctation or interruption. The
patient benefited from a successful surgical commissurotomy of the aortic valve
and reconstruction of the aortic arch with a homograft. The post-operative CMR
confirmed the good surgical result. This case emphasizes the utility of CMR to
provide good anatomical information to establish the exact diagnosis and the
operative strategy.
PMID- 25853110
TI - Closed catheter access system implementation in reducing the bloodstream
infection rate in low birth weight preterm infants.
AB - BACKGROUND: Bloodstream infection (BSI) is one of the significant causes of
morbidity and mortality encountered in a neonatal intensive care unit, especially
in developing countries. Despite the implementation of infection control
practices, such as strict hand hygiene, the BSI rate in our hospital is still
high. The use of a closed catheter access system to reduce BSI related to
intravascular catheter has hitherto never been evaluated in our hospital.
OBJECTIVE: To determine the effects of closed catheter access system
implementation in reducing the BSI rate in preterm neonates with low birth
weight. METHODS: Randomized clinical trial was conducted on 60 low birth weight
preterm infants hospitalized in the neonatal unit at Cipto Mangunkusumo Hospital,
Jakarta, Indonesia from June to September 2013. Randomized subjects either
received a closed or non-closed catheter access system. Subjects were monitored
for 2 weeks for the development of BSI based on clinical signs, abnormal
infection parameters, and blood culture. RESULTS: Closed catheter access system
implementation gave a protective effect toward the occurrence of culture-proven
BSI (relative risk 0.095, 95% CI 0.011-0.85, p = 0.026). Risk of culture-proven
BSI in the control group was 10.545 (95% CI 1.227-90.662, p = 0.026). BSI
occurred in 75% of neonates without risk factors of infection in the control
group compared to none in the study group. CONCLUSION: The use of a closed
catheter access system reduced the BSI in low birth weight preterm infants.
Choosing the right device design, proper disinfection of device, and appropriate
frequency of connector change should be done simultaneously.
PMID- 25853112
TI - New treatment perspectives in autism spectrum disorders.
PMID- 25853111
TI - Should we consider alternatives to universal well-child behavioral-developmental
screening?
AB - The prevalence of developmental disabilities in the young age is of the order of
15%. When behavioral and social-emotional disorders, physical impairments, and
sensory disorders are included, the need for special intervention increases to
one out of four children. As the sensitivity and specificity of the best
screening tests are in the range of 70-80%, their predictive value is
controversial. The cost of conducting definitive tests and repeat screening for
those who fail the screening tests is high. Children with severe disorders can be
identified clinically without a screening test. The poor predictability,
difficulty in implementation, and the high costs of developmental testing suggest
that children, particularly those in high-risk communities, might be better
served by implementing intervention programs for all, instead of trying to
identify the outliers through screening.
PMID- 25853113
TI - New records of mosquitoes (Diptera: culicidae) from bolivar state in South
eastern Venezuela, with 27 new species for the state and 5 of them new in the
country.
AB - This is the first part of a series of studies related to mosquito ecological and
biogeographic aspects. A total of 69 mosquito species (Diptera: Culicidae) was
collected in 16 localities sampled in the Gran Sabana Municipality, Canaima
National Park, and Venezuela. Twenty-seven mosquito species are recorded for the
first time from Bolivar State, Venezuela. Five of them species are reported for
the first time in Venezuela: Anopheles malefactor Dyar and Knab (1907); Chagasia
bonneae Root (1927); Chagasia ablusa Harbach (2009); Culex anduzei Lane (1944),
and Uranotaenia leucoptera Theobald (1907). Their medical importance is
commented, and ecological and epidemiological aspects are discussed. A checklist
of the mosquito species reported in the Gran Sabana County is given.
PMID- 25853114
TI - Promoting public health through state cancer control plans: a review of capacity
and sustainability.
AB - The Centers for Disease Prevention and Control's National Comprehensive Cancer
Control (CCC) Program oversee CCC programs designed to develop and implement CCC
plans via CCC coalitions, alliances, or consortia of program stakeholders. We
reviewed 40 up-to-date plans for states and the District of Columbia in order to
assess how capacity building and sustainability, two evidence-based practices
necessary for organizational readiness, positive growth, and maintenance are
addressed. We employed an electronic key word search, supplemented by full text
reviews of each plan to complete a content analysis of the CCC plans. Capacity is
explicitly addressed in just over half of the plans (53%), generally from a
conceptual point of view, with few specifics as to how capacity will be developed
or enhanced. Roles and responsibilities, timelines for action, and measurements
for evaluation of capacity building are infrequently mentioned. Almost all (92%)
of the 40 up-to-date plans address sustainability on at least a cursory level,
through efforts aimed at funding or seeking funding, policy initiatives, and/or
partnership development. However, few details as to how these strategies will be
implemented are found in the plans. We present the Texas plan as a case study
offering detailed insight into how one plan incorporated capacity building and
sustainability into its development and implementation. Training, technical
assistance, templates, and tools may help CCC coalition members address capacity
and sustainability in future planning efforts and assure the inclusion of
capacity building and sustainability approaches in CCC plans at the state,
tribal, territorial, and jurisdiction levels.
PMID- 25853115
TI - Corrigendum: use of emerging technologies to assess differences in outdoor
physical activity in st. Louis, missouri.
AB - [This corrects the article on p. 41 in vol. 2, PMID: 24904908.].
PMID- 25853117
TI - Additional Evaluation of the Point-of-Contact Circulating Cathodic Antigen Assay
for Schistosoma mansoni Infection.
AB - Studies of the urine-based point-of-contact cathodic circulating antigen test
(POC-CCA) in Schistosoma mansoni-endemic settings in Africa indicate it has good
sensitivity in detecting infections, but in areas of low prevalence, the POC-CCA
can be positive for persons who are egg-negative by Kato-Katz stool assays. We
examined the POC-CCA assay for: (a) batch-to-batch stability; (b) intra-reader
and inter-reader variability; (c) day-to-day variability compared to Kato-Katz
stool assays, and (d) to see if praziquantel (PZQ) treatment converted Kato-Katz
negative/POC-CCA positive individuals to POC-CCA negativity. We found essentially
no batch-to-batch variation, negligible intra-reader variability (2%), and
substantial agreement for inter-reader reliability. Some day-to-day variation was
observed over 5 days of urine collection, but less than the variation in Kato
Katz stool assays over 3 days. To evaluate the effect of treatment on Kato-Katz(
)/POC-CCA(+) children, 149 children in an area of 10-15% prevalence who were Kato
Katz(-) based on 3 stool samples but POC-CCA(+) were enrolled. Seven days after
treatment (PZQ 40 mg/kg) samples were again collected and tested. Almost half
(47%) POC-CCA positive children turned negative. Those still POC-CCA positive
received a second treatment, and 34% of them turned POC-CCA negative upon this
second treatment. Most who remained POC-CCA positive shifted each time to a
"lesser" POC-CCA "level of positivity." The data suggest that most Kato-Katz
negative/POC-CCA positive individuals harbor low-intensity infections, and each
treatment kills all or some of their adult worms. The data also suggest that when
evaluated by a more sensitive assay, the effective cure rates for PZQ are
significantly less than those inferred from fecal testing. These findings have
public health significance for the mapping and monitoring of Schistosoma
infections and in planning the transition from schistosomiasis morbidity control
to elimination of transmission.
PMID- 25853116
TI - The Association between Depressive Symptoms and Physical Diseases in Switzerland:
A Cross-Sectional General Population Study.
AB - OBJECTIVE: To estimate the association between depressive symptoms and physical
diseases in Switzerland, as respective findings might inform about future
estimates of mental and physical health care costs. METHODS: A population-based
study, using data from the Swiss Health Survey collected by computer-assisted
telephone interviews and additional written questionnaires during the year 2007
(n = 18,760) in Switzerland. The multistage stratified random sample included
subjects aged 15 years and older, living in a private Swiss household with a
telephone connection. Complete data were available for 14,348 subjects (51% of
all subjects reached by telephone). Logistic regression analyses were used to
estimate the associations between depressive symptoms and any physical disease,
or a specific physical disease out of 13 non-communicable physical diseases
assessed with a self-report checklist on common physical diseases. Analyses were
adjusted for sex, age, education, occupation, and household income. RESULTS: In
the adjusted models, depressive symptoms were associated with arthrosis and
arthritis [Odds Ratio (OR) = 1.79, 95% confidence interval (CI) = 1.28-2.50] and
any physical disease (OR = 1.67, 95% CI = 1.33-2.10) after controlling for
multiple testing. CONCLUSION: Our findings contribute to a better understanding
of the comorbidity of depressive symptoms and arthrosis and arthritis in
Switzerland and might have implications for more precise future estimates of
mental and physical health care costs.
PMID- 25853118
TI - Economic Impact of Leading Prosperity Diseases: COPD in South East Europe.
PMID- 25853120
TI - Radiation-induced formation of purine lesions in single and double stranded DNA:
revised quantification.
AB - The formation of oxidative lesions arising from double stranded DNA damage is of
major significance to chemical biology from the perspective of application to
human health. The quantification of purine lesions arising from gamma-radiation
induced hydroxyl radicals (HO(*)) has been the subject of numerous studies, with
discrepancies on the measured 5',8-cyclo-2'-deoxyadenosine (cdA) and 5',8-cyclo
2'-deoxyguanosine (cdG) lesions reported by different groups. Here we applied an
ameliorative protocol for the analysis of DNA damage with quantitative
determination of these lesions via isotope dilution liquid chromatography coupled
with tandem mass spectrometry. Tandem-type purine lesions were quantified along
with 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) and 7,8-dihydro-8-oxo-2'
deoxyadenosine (8-oxo-dA) in single and double stranded DNA, generated during DNA
exposure to diffusible HO(*) radicals in the absence or presence of physiological
levels of oxygen. The cdA and cdG lesions in absence of oxygen were found ~2
times higher in single than double stranded DNA, with 5'R being ~6.5 and ~1.5
times more predominant than 5'S in cdG and cdA, respectively. Interestingly, in
the presence of 5% molecular oxygen the R/S ratios are retained with
substantially decreased yields for cdA and cdG, whereas 8-oxo-dA and 8-oxo-dG
remain nearly constant. The overall lesion formation follows the order: 8-oxo-dG
>> 8-oxo-dA > 5'R-cdG > 5'R-cdA > 5'S-cdA > 5'S-cdG. By this method, there was a
conclusive evaluation of radiation-induced DNA purine lesions.
PMID- 25853119
TI - The elusive nature and diagnostics of misfolded Abeta oligomers.
AB - Amyloid-beta (Abeta) peptide oligomers are believed to be the causative agents of
Alzheimer's disease (AD). Though post-mortem examination shows that insoluble
fibrils are deposited in the brains of AD patients in the form of intracellular
(tangles) and extracellular (plaques) deposits, it has been observed that
cognitive impairment is linked to synaptic dysfunction in the stages of the
illness well before the appearance of these mature deposits. Increasing evidence
suggests that the most toxic forms of Abeta are soluble low-oligomer ligands
whose amounts better correlate with the extent of cognitive loss in patients than
the amounts of fibrillar insoluble forms. Therefore, these ligands hold the key
to a better understanding of AD prompting the search for clearer correlations
between their structure and toxicity. The importance of such correlations and
their diagnostic value for the early diagnosis of AD is discussed here with a
particular emphasis on the transient nature and structural plasticity of
misfolded Abeta oligomers.
PMID- 25853121
TI - Total synthesis of the putative structure of the proposed Banyasin A.
AB - The first total synthesis of four possible isomers of a molecule possessing the
configuration proposed for Banyasin A is described. The structure synthesized
appears to be different from that of the natural product.
PMID- 25853122
TI - Unveiling the potential of novel yeast protein extracts in white wines
clarification and stabilization.
AB - Fining agents derived from animal and mineral sources are widely used to clarify
and stabilize white wines. Nevertheless, health and environmental problems are
being raised, concerning the allergenic and environmental impact of some of those
fining products. In this study, our aim is to validate the potential of yeast
protein extracts, obtained from an alternative and safe source, naturally present
in wine: oenological yeasts. Three untreated white wines were used in this work
in order to evaluate the impact of these novel yeast protein extracts (YPE) in
terms of the wine clarification and stabilization improvement. Two separated
fining trials were thus conducted at laboratory scale and the yeast alternatives
were compared with reference fining agents, obtained from mineral, animal and
vegetable origins. Our results indicate that YPE were capable to promote (i)
brilliance/color improvement, (ii) turbidity reduction (76-89% comparing with the
untreated wines), and (iii) production of compact and homogeneous lees (44%
smaller volume than obtained with bentonite). Additionally, after submitting
wines to natural and forced oxidations, YPE treatments revealed (iv) different
forms of colloidal stabilization, by presenting comparable or superior effects
when particularly compared to casein. Altogether, this study reveals that YPE
represent a promising alternative for white wine fining, since they are resultant
from a natural and more sustainable origin, at present not regarded as potential
allergenic according to Regulation (EC) No. 1169/2011.
PMID- 25853123
TI - An easy microwave-assisted synthesis of C8-alkynyl adenine pyranonucleosides as
novel cytotoxic antitumor agents.
AB - We describe the synthesis of C8-alkynyl adenine pyranonucleosides 4, 5, and 8
phenylethynyl-adenine (II), via Sonogashira cross-coupling reaction under
microwave irradiation. Compounds 4e and II were less cytostatic than 5
fluorouracil (almost an order of magnitude) against murine leukemia (L1210) and
human cervix carcinoma (HeLa) cells, while the same compounds proved to be more
active than 5-fluorouracil against human lymphocyte (CEM) cells.
PMID- 25853124
TI - A computational analysis of bone formation in the cranial vault in the mouse.
AB - Bones of the cranial vault are formed by the differentiation of mesenchymal cells
into osteoblasts on a surface that surrounds the brain, eventually forming
mineralized bone. Signaling pathways causative for cell differentiation include
the actions of extracellular proteins driven by information from genes. We assume
that the interaction of cells and extracellular molecules, which are associated
with cell differentiation, can be modeled using Turing's reaction-diffusion
model, a mathematical model for pattern formation controlled by two interacting
molecules (activator and inhibitor). In this study, we hypothesize that regions
of high concentration of an activator develop into primary centers of
ossification, the earliest sites of cranial vault bone. In addition to the Turing
model, we use another diffusion equation to model a morphogen (potentially the
same as the morphogen associated with formation of ossification centers)
associated with bone growth. These mathematical models were solved using the
finite volume method. The computational domain and model parameters are
determined using a large collection of experimental data showing skull bone
formation in mouse at different embryonic days in mice carrying disease causing
mutations and their unaffected littermates. The results show that the relative
locations of the five ossification centers that form in our model occur at the
same position as those identified in experimental data. As bone grows from these
ossification centers, sutures form between the bones.
PMID- 25853125
TI - Statistical approaches to detecting and analyzing tandem repeats in genomic
sequences.
AB - Tandem repeats (TRs) are frequently observed in genomes across all domains of
life. Evidence suggests that some TRs are crucial for proteins with fundamental
biological functions and can be associated with virulence, resistance, and
infectious/neurodegenerative diseases. Genome-scale systematic studies of TRs
have the potential to unveil core mechanisms governing TR evolution and TR roles
in shaping genomes. However, TR-related studies are often non-trivial due to
heterogeneous and sometimes fast evolving TR regions. In this review, we discuss
these intricacies and their consequences. We present our recent contributions to
computational and statistical approaches for TR significance testing, sequence
profile-based TR annotation, TR-aware sequence alignment, phylogenetic analyses
of TR unit number and order, and TR benchmarks. Importantly, all these methods
explicitly rely on the evolutionary definition of a tandem repeat as a sequence
of adjacent repeat units stemming from a common ancestor. The discussed work has
a focus on protein TRs, yet is generally applicable to nucleic acid TRs, sharing
similar features.
PMID- 25853126
TI - Microchamber device for detection of transporter activity of adherent cells.
AB - We present a method to detect the transporter activity of intact adherent cells
using a microchamber device. When adherent cells are seeded onto the poly-di
methyl siloxane substrate having microchambers with openings smaller than the
size of a cell, the cells form a confluent layer that covers the microchambers,
creating minute, confined spaces. As substances exported across the cell membrane
accumulate, transporter activity can be detected by observing the fluorescence
intensity increase in the microchamber. We tested the microchamber device with
HeLa cells over-expressing MDR1, an ATP-binding cassette transporter, and
succeeded in detecting the transport of fluorescence-conjugated paclitaxel, the
anti-cancer drug, at the single-cell level.
PMID- 25853127
TI - Heterogeneity of alkane chain length in freshwater and marine cyanobacteria.
AB - The potential utilization of cyanobacteria for the biological production of
alkanes represents an exceptional system for the next generation of biofuels.
Here, we analyzed a diverse group of freshwater and marine cyanobacterial
isolates from Indian culture collections for their ability to produce both
alkanes and alkenes. Among the 50 cyanobacterial isolates screened, 32 isolates;
14 freshwater and 18 marine isolates; produced predominantly alkanes. The GC
MS/MS profiles revealed a higher percentage of pentadecane and heptadecane
production for marine and freshwater strains, respectively. Oscillatoria species
were found to be the highest producers of alkanes. Among the freshwater isolates,
Oscillatoria CCC305 produced the maximum alkane level with 0.43 MUg/mg dry cell
weight, while Oscillatoria formosa BDU30603 was the highest producer among the
marine isolates with 0.13 MUg/mg dry cell weight. Culturing these strains under
different media compositions showed that the alkane chain length was not
influenced by the growth medium but was rather an inherent property of the
strains. Analysis of the cellular fatty acid content indicated the presence of
predominantly C16 chain length fatty acids in marine strains, while the
proportion of C18 chain length fatty acids increased in the majority of
freshwater strains. These results correlated with alkane chain length specificity
of marine and freshwater isolates indicating that alkane chain lengths may be
primarily determined by the fatty acid synthesis pathway. Moreover, the
phylogenetic analysis showed clustering of pentadecane-producing marine strains
that was distinct from heptadecane-producing freshwater strains strongly
suggesting a close association between alkane chain length and the cyanobacteria
habitat.
PMID- 25853128
TI - Learning to Classify Organic and Conventional Wheat - A Machine Learning Driven
Approach Using the MeltDB 2.0 Metabolomics Analysis Platform.
AB - We present results of our machine learning approach to the problem of classifying
GC-MS data originating from wheat grains of different farming systems. The aim is
to investigate the potential of learning algorithms to classify GC-MS data to be
either from conventionally grown or from organically grown samples and
considering different cultivars. The motivation of our work is rather obvious
nowadays: increased demand for organic food in post-industrialized societies and
the necessity to prove organic food authenticity. The background of our data set
is given by up to 11 wheat cultivars that have been cultivated in both farming
systems, organic and conventional, throughout 3 years. More than 300 GC-MS
measurements were recorded and subsequently processed and analyzed in the MeltDB
2.0 metabolomics analysis platform, being briefly outlined in this paper. We
further describe how unsupervised (t-SNE, PCA) and supervised (SVM) methods can
be applied for sample visualization and classification. Our results clearly show
that years have most and wheat cultivars have second-most influence on the
metabolic composition of a sample. We can also show that for a given year and
cultivar, organic and conventional cultivation can be distinguished by machine
learning algorithms.
PMID- 25853129
TI - Photosynthetic constraints on fuel from microbes.
PMID- 25853130
TI - RobOKoD: microbial strain design for (over)production of target compounds.
AB - Sustainable production of target compounds such as biofuels and high-value
chemicals for pharmaceutical, agrochemical, and chemical industries is becoming
an increasing priority given their current dependency upon diminishing
petrochemical resources. Designing these strains is difficult, with current
methods focusing primarily on knocking-out genes, dismissing other vital steps of
strain design including the overexpression and dampening of genes. The design
predictions from current methods also do not translate well-into successful
strains in the laboratory. Here, we introduce RobOKoD (Robust, Overexpression,
Knockout and Dampening), a method for predicting strain designs for
overproduction of targets. The method uses flux variability analysis to profile
each reaction within the system under differing production percentages of target
compound and biomass. Using these profiles, reactions are identified as potential
knockout, overexpression, or dampening targets. The identified reactions are
ranked according to their suitability, providing flexibility in strain design for
users. The software was tested by designing a butanol-producing Escherichia coli
strain, and was compared against the popular OptKnock and RobustKnock methods.
RobOKoD shows favorable design predictions, when predictions from these methods
are compared to a successful butanol-producing experimentally-validated strain.
Overall RobOKoD provides users with rankings of predicted beneficial genetic
interventions with which to support optimized strain design.
PMID- 25853131
TI - Blood disorders typically associated with renal transplantation.
AB - Renal transplantation has become one of the most common surgical procedures
performed to replace a diseased kidney with a healthy kidney from a donor. It can
help patients with kidney failure live decades longer. However, renal
transplantation also faces a risk of developing various blood disorders. The
blood disorders typically associated with renal transplantation can be divided
into two main categories: (1) Common disorders including post-transplant anemia
(PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant
erythrocytosis (PTE), and post-transplant cytopenias (PTC,
leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but
serious disorders including hemophagocytic syndrome (HPS), thrombotic
microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy
related acute myeloid leukemia (t-AML). Although many etiological factors involve
the development of post-transplant blood disorders, immunosuppressive agents, and
viral infections could be the two major contributors to most blood disorders and
cause hematological abnormalities and immunodeficiency by suppressing
hematopoietic function of bone marrow. Hematological abnormalities and
immunodeficiency will result in severe clinical outcomes in renal transplant
recipients. Understanding how blood disorders develop will help cure these life
threatening complications. A potential therapeutic strategy against post
transplant blood disorders should focus on tapering immunosuppression or
replacing myelotoxic immunosuppressive drugs with lower toxic alternatives,
recognizing and treating promptly the etiological virus, bacteria, or protozoan,
restoring both hematopoietic function of bone marrow and normal blood counts, and
improving kidney graft survival.
PMID- 25853132
TI - Introduction to radiobiology of targeted radionuclide therapy.
AB - During the last decades, new radionuclide-based targeted therapies have emerged
as efficient tools for cancer treatment. Targeted radionuclide therapies (TRTs)
are based on a multidisciplinary approach that involves the cooperation of
specialists in several research fields. Among them, radiobiologists investigate
the biological effects of ionizing radiation, specifically the molecular and
cellular mechanisms involved in the radiation response. Most of the knowledge
about radiation effects concerns external beam radiation therapy (EBRT) and
radiobiology has then strongly contributed to the development of this therapeutic
approach. Similarly, radiobiology and dosimetry are also assumed to be ways for
improving TRT, in particular in the therapy of solid tumors, which are
radioresistant. However, extrapolation of EBRT radiobiology to TRT is not
straightforward. Indeed, the specific physical characteristics of TRT
(heterogeneous and mixed irradiation, protracted exposure, and low absorbed dose
rate) differ from those of conventional EBRT (homogeneous irradiation, short
exposure, and high absorbed dose rate), and consequently the response of
irradiated tissues might be different. Therefore, specific TRT radiobiology needs
to be explored. Determining dose-effect correlation is also a prerequisite for
rigorous preclinical radiobiology studies because dosimetry provides the
necessary referential to all TRT situations. It is required too for developing
patient-tailored TRT in the clinic in order to estimate the best dose for tumor
control, while protecting the healthy tissues, thereby improving therapeutic
efficacy. Finally, it will allow to determine the relative contribution of
targeted effects (assumed to be dose-related) and non-targeted effects (assumed
to be non-dose-related) of ionizing radiation. However, conversely to EBRT where
it is routinely used, dosimetry is still challenging in TRT. Therefore, it
constitutes with radiobiology, one of the main challenges of TRT in the future.
PMID- 25853133
TI - A case report of adrenocorticotropic hormone to treat recurrent focal segmental
glomerular sclerosis post-transplantation and biomarker monitoring.
AB - BACKGROUND: Recurrent focal segmental glomerular sclerosis (rFSGS) in renal
transplant recipients (RTR) is difficult to predict and treat. Early rFSGS is
likely from circulating factors and preformed antibodies. METHODS: We present the
case of a 23-year-old white man who presented with rFSGS and acute renal failure,
requiring dialysis 9-months after a 1-haplotype matched living-related
transplant. We retrospectively analyzed serum samples from various clinical
stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb),
soluble urokinase-type plasminogen activator receptor (suPAR) serum level with
suPAR-beta3 integrin signaling on human podocytes, and angiotensin II type I
receptor-antibody (AT1R-Ab) titer. RESULTS: All biomarkers were abnormal at 1
year pre-transplant prior to initiation of dialysis and at the time of
transplant. After initiation of hemodialysis, beta3 integrin activity on human
podocytes, in response to patient serum, as well as AT1R-Ab were further
elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally
high. One week after therapy with aborted plasmapheresis (secondary to
intolerance), and high dose steroids, the Palb and suPAR-beta3 integrin activity
remained significantly positive. After 12-weeks of treatment with high-dose
steroids, rituximab, and galactose, the patient remained hemodialysis-dependent.
Three-months after his initial presentation, we commenced adrenocorticotropic
hormone (ACTH, Acthar((r)) Gel), 80 units subcutaneously twice weekly. Four-weeks
later, he was able to discontinue dialysis. After 8-months of maintenance ACTH
therapy, his serum creatinine stabilized at 1.79 mg/dL with <1 g of proteinuria.
CONCLUSION: ACTH therapy was associated with improvement in renal function within
4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.
PMID- 25853134
TI - Neuroinflammation induced by intracerebroventricular injection of microbial
neuraminidase.
AB - In the present paper, we describe the facts that took place in the rat brain
after a single injection of the enzyme neuraminidase from Clostridium perfringens
into the right lateral ventricle. After injection, it diffused through the
cerebrospinal fluid of the ipsilateral ventricle and the third ventricle, and
about 400 MUm into the periventricular brain parenchyma. The expression of ICAM1
in the endothelial cells of the periventricular vessels, IBA1 in microglia, and
GFAP in astrocytes notably increased in the regions reached by the injected
neuraminidase. The subependymal microglia and the ventricular macrophages begun
to express IL1beta and some appeared to cross the ependymal layer. After about 4
h of the injection, leukocytes migrated from large venules of the affected
choroid plexus, the meninges and the local subependyma, and infiltrated the
brain. The invading cells arrived orderly: first neutrophils, then macrophage
monocytes, and last CD8alpha-positive T-lymphocytes and B-lymphocytes. Leukocytes
in the ventricles and the perivascular zones penetrated the brain parenchyma
passing through the ependyma and the glia limitans. Thus, it is likely that a
great part of the damage produced by microorganism invading the brain may be due
to their neuraminidase content.
PMID- 25853135
TI - The beneficial role of retinoids in glomerular disease.
AB - The primary etiology of CKD is a direct consequence of initial dysfunction and
injury of the glomerulus, the main filtration system. Podocytes are terminally
differentiated epithelial cells in the glomerulus, whose major function is the
maintenance of this renal filtration barrier. Podocyte injury is implicated in
many glomerular diseases including focal segmental glomerular sclerosis and HIV
associated nephropathy. In many of these diseased conditions, the podocyte can
either undergo dedifferentiation and proliferation, apoptosis, or cell
detachment. Regardless of the initial type of injury, the podocyte ultimately
loses its functional capacity to maintain the glomerular filtration barrier.
Significant injury resulting in a loss of the podocytes and failure to maintain
the renal filtration barrier contributes to progressive kidney disease.
Consequently, therapies that prevent podocyte injury and promote their
regeneration will have a major clinical impact on glomerular disease. Retinoic
acid (RA), which is a derivative of vitamin A, has many cellular functions
including induction of cell differentiation, regulation of apoptosis, and
inhibition of inflammation and proliferation. RA is required for kidney
development and is essential for cellular differentiation in the setting of
podocyte injury. The mechanism by which RA directs its beneficial effects is
multifactorial, ranging from its anti-inflammatory and anti-fibrotic effects to a
direct effect of upregulating podocyte differentiation markers in the podocyte.
The focus of this review is to provide an overview of RA in kidney development
and glomerular disease. We also highlight the key mechanism(s) by which RA
restores podocyte differentiation markers and ameliorates glomerular disease.
PMID- 25853136
TI - The importance of evaluating primary midwifery care for improving the health of
women and infants.
AB - In most countries, maternal and newborn care is fragmented and focused on
identification and treatment of pathology that affects only the minority of women
and babies. Recently, a framework for quality maternal and newborn care was
developed, which encourages a system-level shift to provide skilled care for all.
This care includes preventive and supportive care that works to strengthen
women's capabilities and focuses on promotion of normal reproductive processes
while ensuring access to emergency treatment when needed. Midwifery care is
pivotal in this framework, which contains several elements that resonate with the
main dimensions of primary care. Primary health care is the first level of
contact with the health system where most of the population's curative and
preventive health needs can be fulfilled as close as possible to where people
live and work. In this paper, we argue that midwifery as described in the
framework requires the application of a primary care philosophy for all
childbearing women and infants. Evaluation of the implementation of the framework
should therefore include tools to monitor the performance of primary midwifery
care.
PMID- 25853137
TI - A review of the nonpressor and nonantidiuretic actions of the hormone
vasopressin.
AB - The pressor and antidiuretic actions of arginine vasopressin (AVP) have been well
documented. This review focuses on the less widely appreciated actions of AVP
which also have important physiologic functions and when better understood may
provide important insights into common disease states. These actions include
effects on pain perception and bone structure as well as important relationships
to the varied components of metabolic syndrome. These include effects on blood
glucose, lipid levels, and blood pressure. AVP may also play a role in the
progression of chronic kidney disease and effect physiologic changes relating to
aging, abnormal social behavior, and cognitive function. Important cellular
responses including cell proliferation, inflammation, and control of infection
and their relationship to AVP are described. Finally, the effects of AVP on
hemostasis and the hypothalamic-pituitary-adrenal axis are noted. The goal of
this summary of the various actions of AVP is to direct attention to the
potential benefits of research in these underemphasized areas of importance.
PMID- 25853138
TI - Molecular cloning and characterization of novel phytocystatin gene from turmeric,
Curcuma longa.
AB - Phytocystatin, a type of protease inhibitor (PI), plays major roles in plant
defense mechanisms and has been reported to show antipathogenic properties and
plant stress tolerance. Recombinant plant PIs are gaining popularity as potential
candidates in engineering of crop protection and in synthesizing medicine. It is
therefore crucial to identify PI from novel sources like Curcuma longa as it is
more effective in combating against pathogens due to its novelty. In this study,
a novel cDNA fragment encoding phytocystatin was isolated using degenerate PCR
primers, designed from consensus regions of phytocystatin from other plant
species. A full-length cDNA of the phytocystatin gene, designated CypCl, was
acquired using 5'/3' rapid amplification of cDNA ends method and it has been
deposited in NCBI database (accession number KF545954.1). It has a 687 bp long
open reading frame (ORF) which encodes 228 amino acids. BLAST result indicated
that CypCl is similar to cystatin protease inhibitor from Cucumis sativus with
74% max identity. Sequence analysis showed that CypCl contains most of the motifs
found in a cystatin, including a G residue, LARFAV-, QxVxG sequence, PW
dipeptide, and SNSL sequence at C-terminal extension. Phylogenetic studies also
showed that CypCl is related to phytocystatin from Elaeis guineensis.
PMID- 25853139
TI - Neuronal nitric oxide synthase is dislocated in type I fibers of myalgic muscle
but can recover with physical exercise training.
AB - Trapezius myalgia is the most common type of chronic neck pain. While physical
exercise reduces pain and improves muscle function, the underlying mechanisms
remain unclear. Nitric oxide (NO) signaling is important in modulating cellular
function, and a dysfunctional neuronal NO synthase (nNOS) may contribute to an
ineffective muscle function. This study investigated nNOS expression and
localization in chronically painful muscle. Forty-one women clinically diagnosed
with trapezius myalgia (MYA) and 18 healthy controls (CON) were included in the
case-control study. Subsequently, MYA were randomly assigned to either 10 weeks
of specific strength training (SST, n = 18), general fitness training (GFT, n =
15), or health information (REF, n = 8). Distribution of fiber type, cross
sectional area, and sarcolemmal nNOS expression did not differ between MYA and
CON. However, MYA showed increased sarcoplasmic nNOS localization (18.8 +/- 12
versus 12.8 +/- 8%, P = 0.049) compared with CON. SST resulted in a decrease of
sarcoplasm-localized nNOS following training (before 18.1 +/- 12 versus after
12.0 +/- 12%; P = 0,027). We demonstrate that myalgic muscle displays altered
nNOS localization and that 10 weeks of strength training normalize these
disruptions, which supports previous findings of impaired muscle oxygenation
during work tasks and reduced pain following exercise.
PMID- 25853140
TI - Imbalance of the nerve growth factor and its precursor as a potential biomarker
for diabetic retinopathy.
AB - Our previous studies have demonstrated that diabetes-induced oxidative stress
alters homeostasis of retinal nerve growth factor (NGF) resulting in accumulation
of its precursor, proNGF, at the expense of NGF which plays a critical role in
preserving neuronal and retinal function. This imbalance coincided with retinal
damage in experimental diabetes. Here we test the hypothesis that alteration of
proNGF and NGF levels observed in retina and vitreous will be mirrored in serum
of diabetic patients. Blood and vitreous samples were collected from patients
(diabetic and nondiabetic) undergoing vitrectomy at Georgia Regents University
under approved IRB. Levels of proNGF, NGF, and p75(NTR) shedding were detected
using Western blot analysis. MMP-7 activity was also assayed. Diabetes-induced
proNGF expression and impaired NGF expression were observed in vitreous and
serum. Vitreous and sera from diabetic patients (n = 11) showed significant 40.8
fold and 3.6-fold increases, respectively, compared to nondiabetics (n = 9). In
contrast, vitreous and sera from diabetic patients showed significant 44% and 64%
reductions in NGF levels, respectively, compared to nondiabetics. ProNGF to NGF
ratios showed significant correlation between vitreous and serum. Further
characterization of diabetes-induced imbalance in the proNGF to NGF ratio will
facilitate its utility as an early biomarker for diabetic complications.
PMID- 25853143
TI - Retracted: Variations in stable carbon isotope composition and leaf traits of
Picea schrenkiana var. tianschanica along an altitude gradient in Tianshan
Mountains, Northwest China.
AB - [This retracts the article DOI: 10.1155/2014/243159.].
PMID- 25853142
TI - Cost-effectiveness of anticoagulation in patients with nonvalvular atrial
fibrillation with edoxaban compared to warfarin in Germany.
AB - We compared the cost-utility analysis for edoxaban at both doses with that of
dabigatran at both doses, rivaroxaban, and apixaban (non vitamin K antagonist
oral anticoagulants, NOAC) in a German population. Data of clinical outcome
events were taken from edoxaban's ENGAGE-AF, dabigatran's RE-LY, rivaroxaban's
ROCKET, and apixaban's ARISTOTLE trials. The base-case analyses of a 65-year-old
person with a CHADS2 score >1 gained 0.17 and 0.21 quality-adjusted life years
over warfarin for 30 mg od and 60 mg od edoxaban, respectively. The incremental
cost-effectiveness ratio was 50.000 and 68.000 euro per quality-adjusted life
years for the higher and lower dose of edoxaban (Monte Carlo simulation). These
findings were also similar to those for apixaban and more cost-effective than the
other NOAC regimens. The current market costs for direct oral anticoagulants are
high in relation to the quality of life gained from a German public health care
insurance perspective. The willingness-to-pay threshold was lowest for 60 mg
edoxaban compared to all direct oral anticoagulants and for 30 mg edoxaban
compared to dabigatran and rivaroxaban.
PMID- 25853144
TI - Physiological responses of Kosteletzkya virginica to coastal wetland soil.
AB - Effects of salinity on growth and physiological indices of Kosteletzkya virginica
seedlings were studied. Plant height, fresh weight (FW), dry weight (DW), and net
photosynthetic rate (Pn) increased at 100 mM NaCl and slightly declined at 200
mM, but higher salinity induced a significant reduction. Chlorophyll content,
stomatal conductance (Gs), intercellular CO2 concentration (Ci), and
transpiration rate (E) were not affected under moderate salinities, while
markedly decreased at severe salinities except for the increased Ci at 400 mM
NaCl. Furthermore, no significant differences of Fv/Fm and PhiPSII were found at
lower than 200 mM NaCl, whereas higher salinity caused the declines of Fv/Fm,
PhiPSII, and qP similar to Pn, accompanied with higher NPQ. Besides, salt stress
reduced the leaf RWC, but caused the accumulation of proline to alleviate osmotic
pressure. The increased activities of antioxidant enzymes maintained the normal
levels of MDA and relative membrane permeability. To sum up, Kosteletzkya
virginica seedlings have good salt tolerance and this may be partly attributed to
its osmotic regulation and antioxidant capacity which help to maintain water
balance and normal ROS level to ensure the efficient photosynthesis. These
results provided important implications for Kosteletzkya virginica acting as a
promising multiuse species for reclaiming coastal soil.
PMID- 25853141
TI - Modulation of microRNAs by phytochemicals in cancer: underlying mechanisms and
translational significance.
AB - MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that regulate a variety
of biological processes such as differentiation, development, and survival.
Recent studies suggest that miRNAs are dysregulated in cancer and play critical
roles in cancer initiation, progression, and chemoresistance. Therefore,
exploitation of miRNAs as targets for cancer prevention and therapy could be a
promising approach. Extensive evidence suggests that many naturally occurring
phytochemicals regulate the expression of numerous miRNAs involved in the
pathobiology of cancer. Therefore, an understanding of the regulation of miRNAs
by phytochemicals in cancer, their underlying molecular mechanisms, and
functional consequences on tumor pathophysiology may be useful in formulating
novel strategies to combat this devastating disease. These aspects are discussed
in this review paper with an objective of highlighting the significance of these
observations from the translational standpoint.
PMID- 25853145
TI - Formulation and evaluation of galantamine gel as drug reservoir in transdermal
patch delivery system.
AB - Galantamine hydrobromide is formulated in tablets and capsules prescribed through
oral delivery for the treatment of Alzheimer's disease. However, oral delivery of
drugs can cause severe side effects such as nausea, vomiting, and
gastrointestinal disturbance. Transdermal delivery of galantamine hydrobromide
could avoid these unwanted side effects. In this work, galantamine hydrobromide
was formulated in gel drug reservoir which was then fabricated in the transdermal
patch. The in vitro drug release studies revealed that the drug release from the
donor chamber to receptor chamber of Franz diffusion cell was affected by the
amount of polymer, amount of neutralizer, amount of drug, types of permeation
enhancer, and amount of permeation enhancer. Visual observations of the gels
showed that all formulated gels are translucent, homogeneous, smooth, and stable.
These gels have pH in the suitable range for skin. The gel also showed high drug
content uniformity. Hence, this formulation can be further used in the
preparation of transdermal patch drug delivery system.
PMID- 25853147
TI - Covalent incorporation of the surfactant into high internal phase emulsion
templated polymeric foams.
AB - High internal phase emulsions of water in cyclooctene stabilised by sorbitan
monooleate (Span 80) were cured by ring-opening metathesis polymerisation to
release fully open macroporous polymer foams wherein the surfactant was
covalently incorporated into the poly(cyclooctene) strands via chain transfer
reactions.
PMID- 25853148
TI - Porous ZrO2 sheets synthesized using an ionothermal method and their absorption
properties.
AB - In this study, porous ZrO2 sheets were synthesized using an ionothermal method
combined with heat treatments at 400, 600 and 800 degrees C. Following
ionothermal synthesis, NH4Zr2F9 with a sheet-like structure was obtained. After
heat treatment, the NH4Zr2F9 was transformed into monoclinic ZrO2 with a porous
sheet structure. The ZrO2 was characterized using XRD, FT-IR, FE-SEM TEM, TG-DTA,
BET, and zeta potential analysis. The specific surface area of the samples
increased with heat treatment temperature, being 12, 17, and 19 m(2) g(-1) for
400, 600, and 800 degrees C, respectively. In addition, measurement of the zeta
potential of the samples in KCl solution showed that all samples were negatively
charged at pH 7, and had different isoelectric points. Adsorption was evaluated
using methylene blue and methyl orange and the results indicated that samples
heated at different temperatures possessed different selectivities for cationic
and anionic dyes.
PMID- 25853146
TI - Fibrin gel as an injectable biodegradable scaffold and cell carrier for tissue
engineering.
AB - Due to the increasing needs for organ transplantation and a universal shortage of
donated tissues, tissue engineering emerges as a useful approach to engineer
functional tissues. Although different synthetic materials have been used to
fabricate tissue engineering scaffolds, they have many limitations such as the
biocompatibility concerns, the inability to support cell attachment, and
undesirable degradation rate. Fibrin gel, a biopolymeric material, provides
numerous advantages over synthetic materials in functioning as a tissue
engineering scaffold and a cell carrier. Fibrin gel exhibits excellent
biocompatibility, promotes cell attachment, and can degrade in a controllable
manner. Additionally, fibrin gel mimics the natural blood-clotting process and
self-assembles into a polymer network. The ability for fibrin to cure in situ has
been exploited to develop injectable scaffolds for the repair of damaged cardiac
and cartilage tissues. Additionally, fibrin gel has been utilized as a cell
carrier to protect cells from the forces during the application and cell delivery
processes while enhancing the cell viability and tissue regeneration. Here, we
review the recent advancement in developing fibrin-based biomaterials for the
development of injectable tissue engineering scaffold and cell carriers.
PMID- 25853149
TI - Metastatic prostate cancer mimicking thrombotic thrombocytopenic purpura.
PMID- 25853151
TI - World: Industry confronted with child labour issue.
PMID- 25853150
TI - Early or late antibiotic intervention prevents Helicobacter pylori-induced
gastric cancer in a mouse model.
AB - H. pylori infection causes gastritis, peptic ulcers and gastric cancer.
Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer
remains unknown, especially if given after intestinal metaplasia has developed.
H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking
the tumor suppressor p27 do so, thus providing an experimental model of H. pylori
induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8
weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls.
Mice in the eradication arms received antimicrobial therapy (omeprazole,
metronidazole and clarithromycin) either "early" (at 15 weeks post infection,
WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori
determination, histopathology and cytokine/chemokine expression. Persistently
infected mice developed premalignant lesions including high-grade dysplasia,
whereas those given antibiotics did not. Histologic activity scores in the
eradication groups were similar to each other, and were significantly decreased
compared with controls for inflammation, epithelial defects, hyperplasia,
metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received
antibiotics were significantly lower than controls. There were no significant
differences in expression of IFN-gamma, TNF-alpha, IL-1beta, RANTES, MCP-1, MIP
1alpha or MIP-1beta among the three groups. Thus, H. pylori eradication given
either early or late after infection significantly attenuated gastric
inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient
mice model of H. pylori-induced gastric cancer, irrespective of the timing of
antibiotic administration. This was associated with reduced expression of IP-10
and MIG.
PMID- 25853152
TI - USA: Red Cross tobacco funding risks global brand.
PMID- 25853153
TI - Indonesia: Warnings need stronger enforcement.
PMID- 25853155
TI - Enantioselective radical addition to ketimines: a synthetic route towards
alpha,alpha-disubstituted alpha-amino acids.
PMID- 25853154
TI - Membrane trafficking. Preface.
PMID- 25853156
TI - Comments.
PMID- 25853157
TI - Erratum regarding "Pulmonary Hypertension in CKD" (Am J Kidney Dis.
2013;61[4]:612-622).
AB - In the Narrative Review entitled "Pulmonary Hypertension in CKD" that appeared in
the April 2013 issue ofAJKD (Bolignano et al, volume 61, issue 4, pages 612-622),
Fig 1 contained labeling errors, panel B appeared in duplicate, and panel A was
missing.
PMID- 25853158
TI - [Bulletin editorial for Issue 2].
PMID- 25853159
TI - [ Appointments at service centers -- conflicts of interest and predetermined
breaking points].
PMID- 25853160
TI - [Looking into the SHI VSG: pending bills].
PMID- 25853161
TI - [Love in the workplace -- depart or stay?].
PMID- 25853162
TI - Increasing pressure on nurses a major challenge--Trim.
PMID- 25853163
TI - The making of the MECA.
PMID- 25853164
TI - [Canadian advertising on food and beverages to children. New nutrient criteria].
PMID- 25853165
TI - [Osteoarthritis. Eat better, suffer less].
PMID- 25853166
TI - [Liquid sugar].
PMID- 25853167
TI - [Rotavirus].
PMID- 25853168
TI - [A passionate relief].
PMID- 25853169
TI - [From 1932 to 1972. Colony Nurses. Two authors relate how these women have marked
the history of nursing in Quebec].
PMID- 25853170
TI - [Crimes justified by honor. Act to support potential victims].
PMID- 25853171
TI - [Drugs for children. We need more studies].
PMID- 25853172
TI - The impact of note taking style and note availability at retrieval on mock
jurors' recall and recognition of trial information.
AB - Jurors forget critical trial information and what they do recall can be
inaccurate. Jurors' recall of trial information can be enhanced by permitting
them to take notes during a trial onto blank sheets of paper (henceforth called
freestyle note taking). A recent innovation is the trial-ordered-notebook (TON)
for jurors, which is a notebook containing headings outlining the trial
proceedings and which has space beneath each heading for notes. In a direct
comparison, TON note takers recalled more trial information than freestyle note
takers. This study investigated whether or not note taking improves recall as a
result of enhanced encoding or as a result of note access at retrieval. To assess
this, mock jurors watched and freely recalled a trial video with one-fifth taking
no notes, two-fifths taking freestyle notes and two-fifths using TONs. During
retrieval, half of the freestyle and TON note takers could access their notes.
Note taking enhanced recall, with the freestyle note takers and TON note takers
without note access performing equally as well. Note taking therefore enhances
encoding. Recall was greatest for the TON note takers with note access,
suggesting a retrieval enhancement unique to this condition. The theoretical and
applied implications of these findings are discussed.
PMID- 25853173
TI - Early neurone loss in Alzheimer's disease: cortical or subcortical?
AB - Alzheimer's disease (AD) is a degenerative disorder where the distribution of
pathology throughout the brain is not random but follows a predictive pattern
used for pathological staging. While the involvement of defined functional
systems is fairly well established for more advanced stages, the initial sites of
degeneration are still ill defined. The prevailing concept suggests an origin
within the transentorhinal and entorhinal cortex (EC) from where pathology
spreads to other areas. Still, this concept has been challenged recently
suggesting a potential origin of degeneration in nonthalamic subcortical nuclei
giving rise to cortical innervation such as locus coeruleus (LC) and nucleus
basalis of Meynert (NbM). To contribute to the identification of the early site
of degeneration, here, we address the question whether cortical or subcortical
degeneration occurs more early and develops more quickly during progression of
AD. To this end, we stereologically assessed neurone counts in the NbM, LC and EC
layer-II in the same AD patients ranging from preclinical stages to severe
dementia. In all three areas, neurone loss becomes detectable already at
preclinical stages and is clearly manifest at prodromal AD/MCI. At more advanced
AD, cell loss is most pronounced in the NbM > LC > layer-II EC. During early AD,
however, the extent of cell loss is fairly balanced between all three areas
without clear indications for a preference of one area. We can thus not rule out
that there is more than one way of spreading from its site of origin or that
degeneration even occurs independently at several sites in parallel.
PMID- 25853175
TI - The effects of amphotericin B on angiogenesis in chick chorioallantoic membrane.
AB - OBJECTIVE: Amphotericin B (AmB) is widely used as a mainstay in the treatment of
sight-threatening fungal endophthalmitis. From the time that itraconazole was
discovered to have a previously unknown anti-angiogenic activity, we have
suspected that AmB may have possible effects on ocular angiogenesis. The purpose
of this study was to evaluate the in vivo anti-angiogenic effect of AmB in the
chick chorioallantoic membrane (CAM) model. MATERIALS AND METHODS: Atak-S type
fertilized eggs obtained from the Poultry Institution were used. The eggs were
kept under 37 degrees C at 85-90% relative humidity throughout the experiment.
Amphotericin B was prepared in two different concentrations (AmB 125 MUg/1 mL and
0.125 MUg/1 mL). The CAMs treated with sterile distilled water was specified as
controls. About 0.1 mL of each containing 12.5 and 0.0125 ug of AmB,
respectively, were dropped to CAM surface. Thirteen eggs were used for each
group. The results were evaluated at the 48th hour of the administration of the
drugs and recorded by digital camera. RESULTS: A reduction of angiogenesis in CAM
area which treated with 125 MUg/1 mL of AmB was appreciable macroscopically. The
affected areas showed impaired radial arrangement of small vessels with the
presence of avascular zone at periphery. The dose of 0.125 MUg/1 mL AmB did not
show any visible anti-angiogenic effect. Numerous blood vessels with a radially
arranged pattern developed toward the periphery after 48 h of treatment. In the
CAMs that treated with distilled water, physiological angiogenesis was observed
in allantoic vessels. Vessel formation seems to be similar in CAMs treated with
0.125 MUg/1 mL AmB with the presence of visibly non-malformed alive embryos.
CONCLUSIONS: The present study gives the impression that AmB has the capacity to
serve as an anti-angiogenic treatment. As it is a preliminary CAM study only,
further studies on both animals and humans are required.
PMID- 25853174
TI - Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer's
disease.
AB - INTRODUCTION: In early stages of Alzheimer's disease (AD), neurofibrillary
tangles (NFT) are largely restricted to the entorhinal cortex and medial temporal
lobe. At later stages, when clinical symptoms generally occur, NFT involve
widespread limbic and association cortices. At this point in the disease, amyloid
plaques are also abundantly distributed in the cortex. This observation from
human neuropathological studies led us to pose two alternative hypotheses: that
amyloid in the cortex is permissive for the spread of tangles from the medial
temporal lobe, or that these are co-occurring but not causally related events
simply reflecting progression of AD pathology. RESULTS: We now directly test the
hypothesis that cortical amyloid acts as an accelerant for spreading of tangles
beyond the medial temporal lobe. We crossed rTgTauEC transgenic mice that
demonstrate spread of tau from entorhinal cortex to other brain structures at
advanced age with APP/PS1 mice, and examined mice with either NFTs, amyloid
pathology, or both. We show that concurrent amyloid deposition in the cortex 1)
leads to a dramatic increase in the speed of tau propagation and an extraordinary
increase in the spread of tau to distal brain regions, and 2) significantly
increases tau-induced neuronal loss. CONCLUSIONS: These data strongly support the
hypothesis that cortical amyloid accelerates the spread of tangles throughout the
cortex and amplifies tangle-associated neural system failure in AD.
PMID- 25853176
TI - Effects of isotretinoin on the inflammatory markers and the platelet counts in
patients with acne vulgaris.
AB - OBJECTIVE: Oral isotretinoin is an efficient treatment used commonly in treating
the moderate and severe acne. It has various side effects that affect many
systems in the body. In this study, we are planning to examine the possible
effects of the oral isotretinoin on platelet density, mean platelet volume,
neutrophil lymphocyte rate, platelet lymphocyte rate, and red-blood-cell
distribution width level. METHODS: Twenty-eight males and 84 females, 112
patients in total, diagnosed with acne vulgaris and receiving oral isotretinoin
treatment were examined retrospectively. The full blood parameters of the
patients before the treatment and in the third month of the treatment were
recorded. RESULTS: A statistically meaningful increase was observed in the
platelet density, hemoglobin levels. And a statistically significant decrease has
been determined in the red-blood-cell distribution width level while no
meaningful differences were detected in the mean platelet volume, neutrophil
lymphocyte rate, platelet lymphocyte rate, and white blood cell count.
CONCLUSIONS: The oral isotretinoin treatment has been demonstrated as having
increased the platelet density, hemoglobin levels and having decreased red-blood
cell distribution width level significantly.
PMID- 25853177
TI - The ocular surface side effects of an anti-psychotic drug, clozapine.
AB - PURPOSE: The purpose of this study is to investigate the effects of long-term
clozapine usage on tear film stability and corneal topographic parameters.
MATERIAL AND METHODS: The study was conducted between March 2014 and November
2014. Thirty patients who were diagnosed of schizophrenia and have been under
clozapine treatment for 2.73 +/- 0.73 years (range 2-4 years) were involved in
this study (group 1). Thirty healthy subjects (group 2) who have statistically
similar demographic features compared with the group 1, were involved as a
control group. Full ophthalmologic examination with biomicroscopy and indirect
ophthalmoscopy was applied. Corneal topographic parameters were measured using
the Pentacam HR and Schirmer test was done. Statistical analysis of the subjects
was evaluated by using SPSS (for Windows version 16.0; SPSS Inc., Chicago, IL)
program. RESULTS: K1 value was measured as 43.39 +/- 0.17 D (43-43.50 D) and K2
value was measured as 43.39 +/- 0.06 D (43.30-43.50 D) in groups 1 and 2,
respectively. In groups 1 and 2, K2 values were noted as 43.86 +/- 0.27 D (43.50
44.50 D) and 43.72 +/- 0.18 D (43.50-44.00 D), respectively. Central corneal
thickness was found to be 523.93 +/- 15.66 um (495-554 um) and 550.13 +/- 1.03 um
(520-580 um) in groups 1 and 2, respectively. Corneal apex thickness was 525.86
+/- 15.75 um (497-556 um) in group 1 and 551.60 +/- 14.99 um (521-581 um) in
group 2. The corneal thickness of thinnest location was 520.93 +/- 15.60 um (492
551 um) and 548.06 +/- 15.17 um (518-578 um) in groups 1 and 2, respectively.
Corneal volume was determined as 58.13 +/- 3.46 mm(3) (52-64 mm(3)) in group 1
and 60.73 +/- 3.76 mm(3) (54-66 mm(3)) in group 2. The Schirmer test showed
thickness of 3.33 +/- 0.72 mm (2-4 mm) and 13.60 +/- 1.59 mm (11-16 mm) in groups
1 and 2, respectively. The mean fluorescein break-up time was 5.40 +/- 1.50 s (3
8 s) and 12.46 +/- 1.40 s (10-14 s) in groups 1 and 2, respectively. There was a
statistically significant difference in the Schirmer test, fluorescein break-up
time, central corneal thickness, corneal apex, and the thinnest corneal location
thickness between the two groups. CONCLUSION: Clozapine may induce dry eye
syndrome and thus may lead to morphological alterations in corneal parameters
through its anticholinergic and antidopaminergic activities. Because of these
corneal alterations, one should be aware of evaluating patients having diseases
like glaucoma or preoperative selection of corneal refractive surgery candidates.
PMID- 25853179
TI - Vapor Phase Processing of alpha-Fe2O3 Photoelectrodes for Water Splitting: An
Insight into the Structure/Property Interplay.
AB - Harvesting radiant energy to trigger water photoelectrolysis and produce clean
hydrogen is receiving increasing attention in the search of alternative energy
resources. In this regard, hematite (alpha-Fe2O3) nanostructures with controlled
nano-organization have been fabricated and investigated for use as anodes in
photoelectrochemical (PEC) cells. The target systems have been grown on
conductive substrates by plasma enhanced-chemical vapor deposition (PE-CVD) and
subjected to eventual ex situ annealing in air to further tailor their structure
and properties. A detailed multitechnique approach has enabled to elucidate the
interrelations between system characteristics and the generated photocurrent. The
present alpha-Fe2O3 systems are characterized by a high purity and hierarchical
morphologies consisting of nanopyramids/organized dendrites, offering a high
contact area with the electrolyte. PEC data reveal a dramatic response
enhancement upon thermal treatment, related to a more efficient electron
transfer. The reasons underlying such a phenomenon are elucidated and discussed
by transient absorption spectroscopy (TAS) studies of photogenerated charge
carrier kinetics, investigated on different time scales for the first time on PE
CVD Fe2O3 nanostructures.
PMID- 25853181
TI - 25(th) anniversary state-of-the-art expert discussion with Steven S. Rothenberg,
MD, on the evolution of thoracic surgery.
PMID- 25853180
TI - Wheat rusts never sleep but neither do sequencers: will pathogenomics transform
the way plant diseases are managed?
AB - Field pathogenomics adds highly informative data to surveillance surveys by
enabling rapid evaluation of pathogen variability, population structure and host
genotype.
PMID- 25853178
TI - Potent effects of dioscin against liver fibrosis.
AB - We previously reported the promising effects of dioscin against liver injury, but
its effect on liver fibrosis remains unknown. The present work investigated the
activities of dioscin against liver fibrosis and the underlying molecular
mechanisms. Dioscin effectively inhibited the cell viabilities of HSC-T6, LX-2
and primary rat hepatic stellate cells (HSCs), but not hepatocytes. Furthermore,
dioscin markedly increased peroxisome proliferator activated receptor-gamma (PPAR
gamma) expression and significantly reduced a-smooth muscle actin (alpha-SMA),
transforming growth factor-beta1 (TGF-beta1), collagen alpha1 (I) (COL1A1) and
collagen alpha1 (III) (COL3A1) levels in vitro. Notably, dioscin inhibited HSCs
activation and induced apoptosis in activated HSCs. In vivo, dioscin
significantly improved body weight and hydroxylproline, laminin, alpha-SMA, TGF
beta1, COL1A1 and COL3A1 levels, which were confirmed by histopathological
assays. Dioscin facilitated matrix degradation, and exhibited hepatoprotective
effects through the attenuation of oxidative stress and inflammation, in addition
to exerting anti-fibrotic effects through the modulation of the TGF-beta1/Smad,
Wnt/beta-catenin, mitogen-activated protein kinase (MAPK) and mitochondrial
signaling pathways, which triggered the senescence of activated HSCs. In
conclusion, dioscin exhibited potent effects against liver fibrosis through the
modulation of multiple targets and signaling pathways and should be developed as
a novel candidate for the treatment of liver fibrosis in the future.
PMID- 25853182
TI - Robotic-assisted laparoscopic surgery of urachal anomalies: a single-center
experience.
AB - OBJECTIVES: Urachal anomalies typically arise from abnormalities in the process
of urachal closure. Urachal pathology causes morbidity (pain, umbilical drainage)
and may harbor malignancy. Robotic-assisted laparoscopic surgery may be an
attractive alternative to the open approach, which has only been studied in rare
case reports. Herein, we report our experience with robotic surgery for benign
urachal anomalies. MATERIALS AND METHODS: From 2007 to 2013, we identified 11
patients (8 adult, 3 pediatric) who underwent robotic-assisted laparoscopic
surgery for urachal pathology. Surgery was performed with a transperitoneal
approach with careful dissection starting lateral to the median umbilical
vessels, ensuring removal of all urachal tissue from the umbilicus to the
bladder. When necessary, cystoscopic evaluation was performed to assist with the
intravesical dissection. Patient demographics, postoperative narcotic use
(morphine milligram equivalents), pathologic data, and operative time were
evaluated. RESULTS: There were 4 female and 7 male patients with a median age of
51 years (range, 12-72 years). Median operative time was 85 minutes (range, 51
224 minutes), and median blood loss was 20 mL (range, 5-400 mL). Only 6 patients
required narcotics for pain control postoperatively, with a median of 7.5 mg of
peroral morphine used. Median length of hospital stay was 1 day (range, 1-2
days), and median duration of catheterization was 5.5 days (range, 1-10 days).
One patient underwent concurrent robotic prostatectomy. Pathology was benign in
all cases. Median follow-up was 15.5 months (range, 1-18 months). Surgery was
well tolerated as only 1 patient had a complication (Clavien class 1; a urinary
tract infection treated with oral antibiotics). CONCLUSIONS: Urachal pathology is
well suited to robotic-assisted laparoscopic surgery. The urachus is immediately
visualized upon entry into the abdomen. The procedure can be performed safely,
with short hospitalization and minimal narcotic pain control required.
PMID- 25853183
TI - A novel spherical magnetic compression device for colorectal anastomosis in a
Swine model.
AB - BACKGROUND: We designed a novel, spherical magnetic compression colorectal
anastomosis device and established a swine model to assess the feasibility and
safety, as well as advantages, of the device. METHODS AND MATERIALS: Fifteen
animals were divided into five groups (sacrificed on Days 3, 5 7, 9, and 14) with
3 in each group. In each group, a magnetic compression device was used in 2
animals (experimental animals), and a stapled device was used in 1 animal
(control animal). Feeding status, bowel movements, the discharge time of the
magnetic anastomosis device, burst pressure, and magnetic field strength were
recorded. Gross anatomical and histological examinations were performed. RESULTS:
The average device discharge time was 7.5 days. The burst pressure increased over
time for both the experimental and control animals. Both the gross anatomical and
histological examinations suggested that the inflammatory reaction was milder.
Healing occurred more quickly, and the incidence of complications was lower for
the experimental animals than for the control animals. CONCLUSIONS: The potential
benefits of the spherical magnetic compression colorectal anastomosis device,
relative to the stapled device, were in terms of effectiveness and complication
incidence, which encourages us to further study its application in
gastrointestinal anastomosis.
PMID- 25853184
TI - Sex, violence and HIV on the inside: cultures of violence, denial, gender
inequality and homophobia negatively influence the health outcomes of those in
closed settings.
AB - To map the context of HIV in closed settings in Papua New Guinea (PNG), semi
structured interviews were undertaken with 56 prisoners and detainees and 60 key
stakeholders. The nature of HIV-related risk differs for detained women and men,
and reflects important gender-based issues present in PNG society more broadly.
Women in detention are vulnerable to sexual violence and exploitation and at
greatest risk of HIV while detained in police holding cells, where they are
typically supervised by male officers, in contrast to prisons, where they have
little contact with male staff. HIV risk for men in prison is associated with
consensual and non-consensual sex; this risk is perpetuated by a pervasive
culture of denial and institutionalised homophobia. The illegal nature of sodomy
and male-to-male sex provides Correctional Services the legal grounds by which to
refuse access to condoms for prisoners. Addressing HIV risk among detained men
and women in PNG requires the reform of legislation, police and prison practices
and an understanding of broader structural problems of gender-based violence and
stigma and discrimination.
PMID- 25853187
TI - Image of the month: Caroli syndrome: central dot sign on CT.
PMID- 25853189
TI - Image of the month: Intraperitoneal abscess drainage using
esophagogastroduodenoscopy.
PMID- 25853188
TI - Image of the month: Hepatic visceral larva migrans.
PMID- 25853190
TI - Image of the month: Heterotopic gastric mucosa of the rectum presenting as rectal
bleeding.
PMID- 25853185
TI - Combinatorial activities of SHORT VEGETATIVE PHASE and FLOWERING LOCUS C define
distinct modes of flowering regulation in Arabidopsis.
AB - BACKGROUND: The initiation of flowering is an important developmental transition
as it marks the beginning of the reproductive phase in plants. The MADS-box
transcription factors (TFs) FLOWERING LOCUS C (FLC) and SHORT VEGETATIVE PHASE
(SVP) form a complex to repress the expression of genes that initiate flowering
in Arabidopsis. Both TFs play a central role in the regulatory network by
conferring seasonal patterns of flowering. However, their interdependence and
biological relevance when acting as a complex have not been extensively studied.
RESULTS: We characterized the effects of both TFs individually and as a complex
on flowering initiation using transcriptome profiling and DNA-binding occupancy.
We find four major clusters regulating transcriptional responses, and that DNA
binding scenarios are highly affected by the presence of the cognate partner.
Remarkably, we identify genes whose regulation depends exclusively on
simultaneous action of both proteins, thus distinguishing between the specificity
of the SVP:FLC complex and that of each TF acting individually. The downstream
targets of the SVP:FLC complex include a higher proportion of genes regulating
floral induction, whereas those bound by either TF independently are biased
towards floral development. Many genes involved in gibberellin-related processes
are bound by the SVP:FLC complex, suggesting that direct regulation of
gibberellin metabolism by FLC and SVP contributes to their effects on flowering.
CONCLUSIONS: The regulatory codes controlled by SVP and FLC were deciphered at
the genome-wide level revealing substantial flexibility based on dependent and
independent DNA binding that may contribute to variation and robustness in the
regulation of flowering.
PMID- 25853191
TI - Video of the month. Modified peroral endoscopic myotomy.
PMID- 25853196
TI - Combination therapy with sorafenib and radiofrequency ablation for BCLC stage 0
B1 hepatocellular carcinoma.
PMID- 25853197
TI - Response to Yang et al.
PMID- 25853198
TI - Is polyethylene glycol superior to miralax-gatorade in bowel preparations for
colonoscopy?
PMID- 25853199
TI - Response to Zhang.
PMID- 25853200
TI - Response to Marasco et al.
PMID- 25853201
TI - Dysbiosis in Celiac disease patients with persistent symptoms on gluten-free
diet: a condition similar to that present in irritable bowel syndrome patients?
PMID- 25853202
TI - Focal liver lesions suspected of being cholangiocarcinomas.
PMID- 25853203
TI - Response to Zanini et al.
PMID- 25853204
TI - Frozen encapsulated stool in recurrent Clostridium difficile: exploring the role
of pills in the treatment hierarchy of fecal microbiota transplant nonresponders.
PMID- 25853205
TI - Assessment of sexual function among inflammatory bowel disease patients.
PMID- 25853206
TI - A rare case of rapid patency capsule disintegration.
PMID- 25853207
TI - Serial fecal microbiota transplantation alters mucosal gene expression in
pediatric ulcerative colitis.
PMID- 25853209
TI - Corrigendum: quality indicators for ERCP.
PMID- 25853210
TI - Corrigendum: methotrexate in chronic active Crohn's disease: a double-blind,
randomized, israeli multicenter trial.
PMID- 25853211
TI - Corrigendum: development of the NIH Patient-Reported Outcomes Measurement
Information System (PROMIS) gastrointestinal symptom scales.
PMID- 25853213
TI - Synthesis of substituted dihydrobenzofurans via tandem S(N)Ar/5-exo-trig
cyclization.
AB - A tandem SNAr/5-exo-trig cyclization reaction is reported that converts N-alkyl-
and -arylimines derived from o-fluorobenzaldehydes into 3-amino-2,3-dihydro-2,2
diarylbenzofurans in moderate to good yields. Diarylmethoxide coupling partners
serve the dual role of nucleophile in the SNAr step and catalytic base in the
cyclization step. With a subset of the substrates, a further base-induced
elimination of the 3-amino-2,3-dihydro-2,2-diarylbenzofuran to a phenolic enamine
was observed.
PMID- 25853214
TI - Development of a Hybrid Tracer for SPECT and Optical Imaging of Bacterial
Infections.
AB - In trauma and orthopedic surgery, infection of implants has a major impact on the
outcome for patients. Infections may develop either during the initial
implantation or during the lifetime of an implant. Both infections, as well as
aseptic loosening of the implant, are reasons for revision of the implants.
Therefore, discrimination between aseptic-mechanical-loosening and septic
bacterial-loosening of implants is critical during selection of a patient
tailored treatment policy. Specific detection and visualization of infections is
a challenge because it is difficult to discriminate infections from inflammation.
An imaging tracer that facilitates bacterial identification in a pre- and
intraoperative setting may aid the workup for patients suspicious of bacterial
infections. In this study we evaluated an antimicrobial peptide conjugated to a
hybrid label, which contains both a radioisotope and a fluorescent dye. After
synthesis of DTPA-Cy5-UBI29-41 and-when necessary-radiolabeling with (111)In
(yield 96.3 +/- 2.7%), in vitro binding to various bacterial strains was
evaluated using radioactivity counting and confocal fluorescence microscopy.
Intramuscular bacterial infections (S. aureus or K. pneumoniae) were also
visualized in vivo using a combined nuclear and fluorescence imaging system. The
indium-111 was chosen as label as it has a well-defined coordination chemistry,
and in pilot studies labeling DTPA-Cy5-UBI29-41 with technetium-99m, we
encountered damage to the Cy5 dye after the reduction with SnCl2. As a reference,
we used the validated tracer (99m)Tc-UBI29-41. Fast renal excretion of (111)In
DTPA-Cy5-UBI29-41 was observed. Target to nontarget (T/NT) ratios were highest at
2 h post injection: radioactivity counting yielded T/NT ratios of 2.82 +/- 0.32
for S. aureus and 2.37 +/- 0.05 for K. pneumoniae. Comparable T/NT ratios with
fluorescence imaging of 2.38 +/- 0.09 for S. aureus and 3.55 +/- 0.31 for K.
pneumoniae were calculated. Ex vivo confocal microscopy of excised infected
tissues showed specific binding of the tracer to bacteria. Using a combination of
nuclear and fluorescence imaging techniques, the hybrid antimicrobial peptide
conjugate DTPA-Cy5-UBI29-41 was shown to specifically accumulate in bacterial
infections. This hybrid tracer may facilitate integration of noninvasive
identification of infections and their extent as well as real-time fluorescence
guidance during surgical resection of infected areas.
PMID- 25853215
TI - Comes Digital Pathology.
PMID- 25853216
TI - Association between small for gestational age and intrauterine fetal death:
comparing a customized South Korean growth standard versus a population-based
fetal growth chart.
AB - OBJECTIVE: To determine if a customized growth standard developed for an
ethnically homogeneous South Korean population is better at identifying (SGA)
fetuses at risk for intra-uterine fetal death (IUFD), compared with a current
population based-growth standard. STUDY DESIGN: A retrospective cohort study
comparing the identification of SGA fetuses at risk for IUFD using a customized
versus a population based-chart. The association between a SGA infant defined as
a birth weight <10th percentile using the South Korean population chart versus
the customized chart and IUFD were compared. Intrauterine fetal death was defined
as fetal demise occurring after 20 weeks gestation. Statistical analyses
including OR, 95% confidence interval (CI), and screening accuracy using each
chart were performed. RESULTS: The customized singleton chart identified 11
(8.2%) of the SGA pregnancies detected by the population chart and classified 15
additional fetuses as SGA. Those identified as SGA using the customized chart had
an OR for IUFD that was approximately 15 times as high as those identified using
the population chart. The customized chart also showed a higher sensitivity and
specificity for identifying SGA pregnancies at risk for IUFD. CONCLUSION: In this
ethnically homogenous population, the customized growth chart showed improved
discrimination in identifying SGA pregnancies at risk for fetal death than the
population-based growth chart.
PMID- 25853217
TI - Human ACAP2 is a homolog of C. elegans CNT-1 that promotes apoptosis in cancer
cells.
AB - Activation of caspases is an integral part of the apoptotic cell death program.
Collectively, these proteases target hundreds of substrates, leading to the
hypothesis that apoptosis is "death by a thousand cuts". Recent work, however,
has demonstrated that caspase cleavage of only a subset of these substrates
directs apoptosis in the cell. One such example is C. elegans CNT-1, which is
cleaved by CED-3 to generate a truncated form, tCNT-1, that acquires a potent
phosphoinositide-binding activity and translocates to the plasma membrane where
it inactivates AKT survival signaling. We report here that ACAP2, a homolog of C.
elegans CNT-1, has a pro-apoptotic function and an identical phosphoinositide
binding pattern to that of tCNT-1, despite not being an apparent target of
caspase cleavage. We show that knockdown of ACAP2 blocks apoptosis in cancer
cells in response to the chemotherapeutic antimetabolite 5-fluorouracil and that
ACAP2 expression is down-regulated in some esophageal cancers, leukemias and
lymphomas. These results suggest that ACAP2 is a functional homolog of C. elegans
CNT-1 and its inactivation or downregulation in human cells may contribute to
cancer development.
PMID- 25853218
TI - In vitro evaluation of genotoxic effects under magnetic resonant coupling
wireless power transfer.
AB - Wireless power transfer (WPT) technology using the resonant coupling phenomenon
has been widely studied, but there are very few studies concerning the possible
relationship between WPT exposure and human health. In this study, we
investigated whether exposure to magnetic resonant coupling WPT has genotoxic
effects on WI38VA13 subcloned 2RA human fibroblast cells. WPT exposure was
performed using a helical coil-based exposure system designed to transfer power
with 85.4% efficiency at a 12.5-MHz resonant frequency. The magnetic field at the
positions of the cell culture dishes is approximately twice the reference level
for occupational exposure as stated in the International Commission on Non
Ionizing Radiation Protection (ICNIRP) guidelines. The specific absorption rate
at the positions of the cell culture dishes matches the respective reference
levels stated in the ICNIRP guidelines. For assessment of genotoxicity, we
studied cell growth, cell cycle distribution, DNA strand breaks using the comet
assay, micronucleus formation, and hypoxanthine-guanine phosphoribosyltransferase
(HPRT) gene mutation, and did not detect any significant effects between the WPT
exposed cells and control cells. Our results suggest that WPT exposure under the
conditions of the ICNIRP guidelines does not cause detectable cellular
genotoxicity.
PMID- 25853219
TI - Healthy vinton: a health impact assessment focused on water and sanitation in a
small rural town on the US-Mexico border.
AB - We conducted a Health Impact Assessment (HIA) focused on water and sanitation in
Vinton, TX, a small rural town on the U.S./Mexico Border. We present the Vinton
HIA as a case study to inform the practice of HIA in rural limited resource
communities with higher than average levels of unemployment and poverty, and
limited infrastructure. Household surveys, focus groups, and interviews provided
quantitative and qualitative data on water sources and quality, sanitation
practices, and community health. We found that some of the current water sources
in Vinton did not meet drinking water standards for total dissolved solids and
arsenic; the majority of septic tanks were not managed properly; and there was a
short-term risk of water scarcity due to prolonged drought in the region.
Prevalent ailments reported by participants included stomach problems, diarrhea,
and skin problems. These ailments can be related to arsenic and/or biological
organisms in water. The positive direct and indirect health impacts of improved
water and sanitation in Vinton included: reduced gastrointestinal illnesses and
skin disorders; improved water quality, quantity, and pressure; reduced risks
from failing septic systems; increased property value; potential economic growth;
and enhanced quality of life. The negative direct and indirect impacts included:
residents' initial and monthly costs; increased property taxes; increased debt by
local government; and the need for ongoing support from changing elected decision
makers. The unique challenges in completing this HIA included: (a) limited
available data; (b) a culture of fear and distrust among residents; (c)
residents' lack of education, awareness, and civic discourse regarding water and
sanitation issues and their impact on public health; and (d) lack of civic
discourse and participation in the democratic process. An important outcome of
the HIA was the characterization of local water supplies, which motivated and
empowered the community members to become more involved in civic discourse
concerning their water supplies. Results are transferable to similar low-income
rural communities worldwide where residents are lacking in information about
their water supplies and in political "voice".
PMID- 25853220
TI - Dual-gated topological insulator thin-film device for efficient Fermi-level
tuning.
AB - Observations of novel quantum phenomena expected for three-dimensional
topological insulators (TIs) often require fabrications of thin-film devices and
tuning of the Fermi level across the Dirac point. Since thin films have both top
and bottom surfaces, an effective control of the surface chemical potential
requires dual gating. However, a reliable dual-gating technique for TI thin films
has not yet been developed. Here we report a comprehensive method to fabricate a
dual-gated TI device and demonstrate tuning of the chemical potential of both
surfaces across the Dirac points. The most important part of our method is the
recipe for safely detaching high-quality, bulk-insulating (Bi(1-x)Sb(x))2Te3 thin
films from sapphire substrates and transferring them to Si/SiO2 wafers that allow
back gating. Fabrication of an efficient top gate by low-temperature deposition
of a SiN(x) dielectric complements the procedure. Our dual-gated devices are
shown to be effective in tuning the chemical potential in a wide range
encompassing the Dirac points on both surfaces.
PMID- 25853223
TI - Modelling catheter-vein biomechanical interactions during an intravenous
procedure.
AB - A reliable intravenous (IV) access into the upper extremity veins requires the
insertion of a temporary short peripheral catheter (SPC). This so common
procedure is, however, associated with a risk of developing short peripheral
catheter thrombophlebitis (SPCT) which causes distress and potentially prolongs
patient hospitalization. We have developed and studied a biomechanical SPC-vein
computational model during an IV procedure, and explored the biomechanical
effects of repeated IV episodes on onset and reoccurrences of SPCT. The model was
used to determine the effects of different insertion techniques as well as inter
patient biological variability on the catheter-vein wall contact pressures and
wall deformations. We found that the maximal pressure exerted upon the vein wall
was inhomogeneously distributed, and that the bending region was exposed to
significantly greater pressures and deformations. The maximal exerted contact
pressure on the inner vein's wall was 2938 Pa. The maximal extent of the SPC
penetration into the vein wall reached 3.6 MUm, which corresponds to
approximately 100% of the average height of the inner layer, suggesting local
squashing of endothelial cells at the contact site. The modelling describes a
potential biomechanical damage pathway that can explain the reoccurrence of SPCT.
PMID- 25853224
TI - Children's judgements of social withdrawal behaviours.
AB - Ding et al. (Brit. J. Dev. Psychol., 2015; 33, 159-173) demonstrated that Chinese
children discriminate between the three subtypes of social withdrawal: Shyness,
unsociability, and social avoidance. This commentary on the Ding et al.'s paper
highlights the need to further explore the following: (1) children's
understanding of the implications of being shy, unsociable, or socially avoidant,
including assessing these which we know are associated with outcomes for socially
withdrawn children; (2) what additional subtypes might exist naturally within the
Chinese culture; and (3) consider the implications of social withdrawal on
children's developing social skills.
PMID- 25853228
TI - Easy To Synthesize, Robust Organo-osmium Asymmetric Transfer Hydrogenation
Catalysts.
AB - Asymmetric transfer hydrogenation (ATH) is an important process in organic
synthesis for which the Noyori-type Ru(II) catalysts [(arene)Ru(Tsdiamine)] are
now well established and widely used. We now demonstrate for the first time the
catalytic activity of the osmium analogues. X-ray crystal structures of the 16
electron Os(II) catalysts are almost identical to those of Ru(II). Intriguingly
the precursor complex was isolated as a dichlorido complex with a monodentate
amine ligand. The Os(II) catalysts are readily synthesised (within 1 h) and
exhibit excellent enantioselectivity in ATH reactions of ketones.
PMID- 25853229
TI - Effects of a worksite program to improve the cardiovascular health of female
health care workers.
AB - PURPOSE: Reducing cardiovascular risk for female health care workers supports
self-care and facilitates a culture of health promotion. We examined the effect
of individualized motivational communications on risk and measured program
participation at a busy hospital, utilizing cardiac rehabilitation resources.
METHODS: Women (40-65 years old) who self-identified as having increased
cardiovascular risk and ready for change were randomly assigned to weekly
motivational counseling or control. All participants were offered classes
(weight/diet, stress, exercise, and smoking cessation) and gym access. Physical
and perceptual measures were recorded before and after the 6-month program to
measure change. Followup 1 year later measured current weight, stress, and
physical activity. RESULTS: Participants (n = 57) ranked weight as their greatest
concern (42%). Compared with control, the intervention group resulted in greater:
weight loss (7.2 vs 3.8 pounds); stress reduction (6.5 vs 4.7; Cohen stress
scale); and exercise days per week (1.4 vs 1.2). Differences were not
statistically significant in this small sample, but all changes consistently
favored the intervention. Program participation was low, as was participation in
the 1-year followup, although those responding indicated maintenance or further
improvement. CONCLUSIONS: These consistent and positive findings are promising
but only suggestive because of the small sample size. Future studies should focus
on how to get more buy-in from employees, to help insure persistence toward
health goals. Study results assisted development of a comprehensive Web-based
employee wellness motivational program to address the issues of on-site
participation. Attention to health risks in health care workers remains an
important area of study.
PMID- 25853230
TI - Theoretical Analysis of the Relative Significance of Thermodynamic and Kinetic
Dispersion in the dc and ac Voltammetry of Surface-Confined Molecules.
AB - Commonly, significant discrepancies are reported in theoretical and experimental
comparisons of dc voltammograms derived from a monolayer or close to monolayer
coverage of redox-active surface-confined molecules. For example, broader-than
predicted voltammetric wave shapes are attributed to the thermodynamic or kinetic
dispersion derived from distributions in reversible potentials (E(0)) and
electrode kinetics (k(0)), respectively. The recent availability of
experimentally estimated distributions of E(0) and k(0) values derived from the
analysis of data for small numbers of surface-confined modified azurin
metalloprotein molecules now allows more realistic modeling to be undertaken,
assuming the same distributions apply under conditions of high surface coverage
relevant to voltammetric experiments. In this work, modeling based on
conventional and stochastic kinetic theory is considered, and the computationally
far more efficient conventional model is shown to be equivalent to the stochastic
one when large numbers of molecules are present. Perhaps unexpectedly, when
experimentally determined distributions of E(0) and k(0) are input into the
model, thermodynamic dispersion is found to be unimportant and only kinetic
dispersion contributes significantly to the broadening of dc voltammograms.
Simulations of ac voltammetric experiments lead to the conclusion that the ac
method, particularly when the analysis of kinetically very sensitive higher-order
harmonics is undertaken, are far more sensitive to kinetic dispersion than the dc
method. ac methods are therefore concluded to provide a potentially superior
strategy for addressing the inverse problem of determining the k(0) distribution
that could give rise to the apparent anomalies in surface-confined voltammetry.
PMID- 25853232
TI - Screening Strategies for Pancreatic Cancer in High-Risk Patients: Opportunities
to Make a Real Impact But Many Questions and Challenges Still Ahead.
PMID- 25853234
TI - Remarkably stable chelating bis-N-heterocyclic carbene adducts of phosphorus(i)
cations.
AB - A convenient one-pot synthesis of chelating bis-N-heterocyclic carbene-ligated
P(I) salts is described. The solid state structures of these remarkably stable
phosphamethine cyanine dyes with various N-alkyl groups and counter-anions are
reported, and initial reactivity results are discussed.
PMID- 25853231
TI - mTORC1 maintains the tumorigenicity of SSEA-4(+) high-grade osteosarcoma.
AB - Inactivation of p53 and/or Rb pathways restrains osteoblasts from cell-cycle exit
and terminal differentiation, which underpins osteosarcoma formation coupled with
dedifferentiation. Recently, the level of p-S6K was shown to independently
predict the prognosis for osteosarcomas, while the reason behind this is not
understood. Here we show that in certain high-grade osteosarcomas, immature SSEA
4(+) tumor cells represent a subset of tumor-initiating cells (TICs) whose pool
size is maintained by mTORC1 activity. mTORC1 supports not only SSEA-4(+) cell
self-renewal through S6K but also the regeneration of SSEA-4(+) TICs by SSEA-4(-)
osteosarcoma cell dedifferentiation. Mechanistically, active mTORC1 is required
to prevent a likely upregulation of the cell-cycle inhibitor p27 independently of
p53 or Rb activation, which otherwise effectively drives the terminal
differentiation of SSEA-4(-) osteosarcoma cells at the expense of
dedifferentiation. Thus, mTORC1 is shown to critically regulate the retention of
tumorigenicity versus differentiation in discrete differentiation phases in SSEA
4(+) TICs and their progeny.
PMID- 25853235
TI - We Pledge to Change iPLEDGE.
PMID- 25853236
TI - A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the
Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan
in Healthy Volunteers at Steady State.
AB - Combining different classes of antihypertensives is more effective for reducing
blood pressure (BP) than increasing the dose of monotherapies. The aims of this
phase I study were to investigate pharmacokinetic and pharmacodynamic
interactions between nebivolol, a vasodilatory beta1-selective blocker, and
valsartan, an angiotensin II receptor blocker, and to assess safety and
tolerability of the combination. This was a single-center, randomized, open
label, multiple-dose, 3-way crossover trial in 30 healthy adults aged 18-45
years. Participants were randomized into 1 of 6 treatment sequences (1:1:1:1:1:1)
consisting of three 7-day treatment periods followed by a 7-day washout. Once
daily oral treatments comprised nebivolol (20 mg), valsartan (320 mg), and
nebivolol-valsartan combination (20/320 mg). Outcomes included AUC0-tau,ss,
Cmax,ss, Tmax,ss, changes in BP, pulse rate, plasma angiotensin II, plasma renin
activity, 24-hour urinary aldosterone, and adverse events. Steady-state
pharmacokinetic interactions were observed but deemed not clinically significant.
Systolic and diastolic BP reduction was significantly greater with nebivolol
valsartan combination than with either monotherapy. The mean pulse rate
associated with nebivolol and nebivolol-valsartan treatments was consistently
lower than that associated with valsartan monotherapy. A sharp increase in mean
day 7 plasma renin activity and plasma angiotensin II that occurred in valsartan
treated participants was significantly attenuated with concomitant nebivolol
administration. Mean 24-hour urine aldosterone at day 7 was substantially
decreased after combined treatment, as compared with either monotherapy. All
treatments were safe and well tolerated. In conclusion, nebivolol and valsartan
coadministration led to greater reductions in BP compared with either
monotherapy; nebivolol and valsartan lower BP through complementary mechanisms.
PMID- 25853237
TI - Low-Molecular-Weight Heparins as Immunomodulators in Dermatology Practice.
AB - Low-molecular-weight heparins (LMWHs) have some effects on cell proliferation and
inflammation beyond mere anticoagulation. They have been tried on treatment of a
few dermatological disorders such as lichen planus, skin wound healing, recurrent
aphtous stomatitis, chronic urticaria, and contact hypersensitivity. LMWHs are
generally well-tolerated drugs, rarely can lead to severe reactions. In this
article, we will review the novel indications of LMWHs in dermatology practice
and common skin reactions associated with their use.
PMID- 25853238
TI - A monocrystal graphene domain biosensor array with differential output for real
time monitoring of glucose and normal saline.
AB - A biosensor array with differential output based on a monocrystal graphene domain
is proposed to realize high resolution measurements. The differential output
structure can eliminate the noise that comes from graphene crystal orientation
and grain boundary, as well as the fluctuation that comes from the contact
resistance and experiment process, so as to improve resolution in the lower
concentration. We have fabricated a high quality monocrystal graphene domain that
has millimeter size by the chemical vapor deposition method. Two identical
graphene ribbons that are cut from the same domain are used as field effect
transistor source-to-drain channels for the reference and the test of
differential output, respectively. The experimental results show that the source
to-drain current has a fast response shorter than 0.5 second in glucose, normal
saline and pH buffer solutions of different concentrations. Sensitivity increases
exponentially with the increase of concentration of the tested liquid and the
high resolution range is 0.01-2 wt% in glucose and 0.0009-0.018 wt% in saline,
and the highest resolutions of glucose and saline are 0.01 wt% and 0.0009 wt%,
respectively. We have fabricated a 1 * 4 array structure with differential
outputs that pave the way for rapidly detecting ultra-low concentration of
analytes.
PMID- 25853239
TI - Reduced gaze following and attention to heads when viewing a "live" social scene.
AB - Social stimuli are known to both attract and direct our attention, but most
research on social attention has been conducted in highly controlled laboratory
settings lacking in social context. This study examined the role of social
context on viewing behaviour of participants whilst they watched a dynamic social
scene, under three different conditions. In two social groups, participants
believed they were watching a live webcam of other participants. The socially
engaged group believed they would later complete a group task with the people in
the video, whilst the non-engaged group believed they would not meet the people
in the scene. In a third condition, participants simply free-viewed the same
video with the knowledge that it was pre-recorded, with no suggestion of a later
interaction. Results demonstrated that the social context in which the stimulus
was viewed significantly influenced viewing behaviour. Specifically, participants
in the social conditions allocated less visual attention towards the heads of the
actors in the scene and followed their gaze less than those in the free-viewing
group. These findings suggest that by underestimating the impact of social
context in social attention, researchers risk coming to inaccurate conclusions
about how we attend to others in the real world.
PMID- 25853240
TI - Associations between renal hyperfiltration and serum alkaline phosphatase.
AB - Renal hyperfiltration, which is associated with renal injury, occurs in diabetic
or obese individuals. Serum alkaline phosphatase (ALP) level is also elevated in
patients with diabetes (DM) or metabolic syndrome (MS), and increased urinary
excretion of ALP has been demonstrated in patients who have hyperfiltration and
tubular damage. However, little was investigated about the association between
hyperfiltration and serum ALP level. A retrospective observational study of the
21,308 adults in the Korea National Health and Nutrition Examination Survey IV-V
databases (2008-2011) was performed. Renal hyperfiltration was defined as
exceeding the age- and sex-specific 97.5th percentile. We divided participants
into 4 groups according to their estimated glomerular filtration rate (eGFR):
>120, 90-119, 60-89, and <60 mL/min/1.73 m2. The participants with eGFR >120
mL/min/1.73 m2 showed the highest risk for MS, in the highest ALP quartiles
(3.848, 95% CI, 1.876-7.892), compared to the lowest quartile. Similarly, the
highest risk for DM, in the highest ALP quartiles, was observed in participants
with eGFR >120 ml/min/1.73 m2 (2.166, 95% CI, 1.084-4.329). ALP quartiles were
significantly associated with albuminuria in participants with eGFR >= 60
ml/min/1.73m2. The highest ALP quartile had a 1.631-fold risk elevation for
albuminuria with adjustment of age and sex. (95% CI, 1.158-2.297, P = 0.005).
After adjustment, the highest ALP quartile had a 1.624-fold risk elevation, for
renal hyperfiltration (95% CI, 1.204-2.192, P = 0.002). In addition,
hyperfiltration was significantly associated with hemoglobin, triglyceride, white
blood cell count, DM, smoking, and alcohol consumption (P<0.05). The relationship
between serum ALP and metabolic disorders is stronger in participants with an
upper-normal range of eGFR. Higher ALP levels are significantly associated with
renal hyperfiltration in Korean general population.
PMID- 25853241
TI - The efficacy of Shugan Jianpi Zhixie therapy for diarrhea-predominant irritable
bowel syndrome: a meta-analysis of randomized, double-blind, placebo-controlled
trials.
AB - BACKGROUND: Shugan Jianpi Zhixie therapy (SJZT) has been widely used to treat
diarrhea-predominant irritable bowel syndrome (IBS-D), but the results are still
controversial. A meta-analysis of randomized, double-blind, placebo-controlled
trials was performed to assess the efficacy and tolerability of SJZT for IBS-D.
METHODS: The MEDLINE, EMBASE, Cochrane Library, the China National Knowledge
Infrastructure database, the Chinese Biomedical Literature database and the
Wanfang database were searched up to June 2014 with no language restrictions.
Summary estimates, including 95% confidence intervals (CI), were calculated for
global symptom improvement, abdominal pain improvement, and Symptom Severity
Scale (BSS) score. RESULTS: Seven trials (N=954) were included. The overall risk
of bias assessment was low. SJZT showed significant improvement for global
symptom compared to placebo (RR 1.61; 95% CI 1.24, 2.10; P =0.0004; therapeutic
gain = 33.0%; number needed to treat (NNT) = 3.0). SJZT was significantly more
likely to reduce overall BSS score (SMD -0.67; 95% CI -0.94, -0.40; P < 0.00001)
and improve abdominal pain (RR 4.34; 95% CI 2.64, 7.14; P < 0.00001) than
placebo. The adverse events of SJZT were no different from those of placebo.
CONCLUSIONS: This meta-analysis suggests that SJZT is an effective and safe
therapy option for patients with IBS-D. However, due to the high clinical
heterogeneity and small sample size of the included trials, further standardized
preparation, large-scale and rigorously designed trials are needed.
PMID- 25853242
TI - High sodium and low potassium intake among Italian children: relationship with
age, body mass and blood pressure.
AB - BACKGROUND: Hypertension is the leading cause of death in developed countries and
reduction of salt intake is recommended as a key preventive measure. OBJECTIVE:
To assess the dietary sodium and potassium intakes in a national sample of
Italian children and adolescents and to examine their relationships with BMI and
blood pressure (BP) in the framework of the MINISAL survey, a program supported
by the Italian Ministry of Health. POPULATION AND METHODS: The study population
included 1424 healthy subjects (766 boys, 658 girls) aged 6-18 years (mean age:
10.1+/-2.9) who were consecutively recruited in participating National Health
Service centers in 10 Italian regions. Electrolyte intake was estimated from 24
hour urine collections tested for completeness by the concomitant measurement of
creatinine content. Anthropometric indices and BP were measured with standardized
procedures. RESULTS: The average estimated sodium intake was 129 mmol (7.4 g of
salt) per day among boys and 117 mmol (6.7 g of salt) among girls. Ninety-three
percent of the boys and 89% of the girls had a consumption higher than the
recommended age-specific standard dietary target. The estimated average daily
potassium intakes were 39 mmol (1.53 g) and 36 mmol (1.40 g), respectively, over
96% of the boys and 98% of the girls having a potassium intake lower than the
recommended adequate intake. The mean sodium/potassium ratio was similar among
boys and girls (3.5 and 3.4, respectively) and over 3-fold greater than the
desirable level. Sodium intake was directly related to age, body mass and BP in
the whole population. CONCLUSIONS: The Italian pediatric population is
characterized by excessive sodium and deficient potassium intake. These data
suggest that future campaigns should focus on children and adolescents as a major
target in the framework of a population strategy of cardiovascular prevention.
PMID- 25853244
TI - Solar radiation during rewarming from torpor in elephant shrews: supplementation
or substitution of endogenous heat production?
AB - Many small mammals bask in the sun during rewarming from heterothermy, but the
implications of this behaviour for their energy balance remain little understood.
Specifically, it remains unclear whether solar radiation supplements endogenous
metabolic thermogenesis (i.e., rewarming occurs through the additive effects of
internally-produced and external heat), or whether solar radiation reduces the
energy required to rewarm by substituting (i.e, replacing) metabolic heat
production. To address this question, we examined patterns of torpor and
rewarming rates in eastern rock elephant shrews (Elephantulus myurus) housed in
outdoor cages with access to either natural levels of solar radiation or levels
that were experimentally reduced by means of shade cloth. We also tested whether
acclimation to solar radiation availability was manifested via phenotypic
flexibility in basal metabolic rate (BMR), non-shivering thermogenesis (NST)
capacity and/or summit metabolism (Msum). Rewarming rates varied significantly
among treatments, with elephant shrews experiencing natural solar radiation
levels rewarming faster than conspecifics experiencing solar radiation levels
equivalent to approximately 20% or 40% of natural levels. BMR differed
significantly between individuals experiencing natural levels of solar radiation
and conspecifics experiencing approximately 20% of natural levels, but no between
treatment difference was evident for NST capacity or Msum. The positive
relationship between solar radiation availability and rewarming rate, together
with the absence of acclimation in maximum non-shivering and total heat
production capacities, suggests that under the conditions of this study solar
radiation supplemented rather than substituted metabolic thermogenesis as a
source of heat during rewarming from heterothermy.
PMID- 25853243
TI - Lysosomal trafficking of TGFBIp via caveolae-mediated endocytosis.
AB - Transforming growth factor-beta-induced protein (TGFBIp) is ubiquitously
expressed in the extracellular matrix (ECM) of various tissues and cell lines.
Progressive accumulation of mutant TGFBIp is directly involved in the
pathogenesis of TGFBI-linked corneal dystrophy. Recent studies reported that
mutant TGFBIp accumulates in cells; however, the trafficking of TGFBIp is poorly
understood. Therefore, we investigated TGFBIp trafficking to determine the route
of its internalization and secretion and to elucidate its roles in the
pathogenesis of granular corneal dystrophy type 2 (GCD2). Our data indicate that
newly synthesized TGFBIp was secreted via the endoplasmic reticulum/Golgi
dependent secretory pathway, and this secretion was delayed in the corneal
fibroblasts of patients with GCD2. We also found that TGFBIp was internalized by
caveolae-mediated endocytosis, and the internalized TGFBIp accumulated after
treatment with bafilomycin A1, an inhibitor of lysosomal degradation. In
addition, the proteasome inhibitor MG132 inhibits the endocytosis of TGFBIp. Co
immunoprecipitation revealed that TGFBIp interacted with integrin alphaVbeta3.
Moreover, treatment with arginine-glycine-aspartic acid (RGD) tripeptide
suppressed the internalization of TGFBIp. These insights on TGFBIp trafficking
could lead to the identification of novel targets and the development of new
therapies for TGFBI-linked corneal dystrophy.
PMID- 25853245
TI - Behaviour and locomotor activity of a migratory catostomid during fishway
passage.
AB - Fishways have been developed to restore longitudinal connectivity in rivers.
Despite their potential for aiding fish passage, fishways may represent a source
of significant energetic expenditure for fish as they are highly turbulent
environments. Nonetheless, our understanding of the physiological mechanisms
underpinning fishway passage of fish is still limited. We examined swimming
behaviour and activity of silver redhorse (Moxostoma anisurum) during its upriver
spawning migration in a vertical slot fishway. We used an accelerometer-derived
instantaneous activity metric (overall dynamic body acceleration) to estimate
location-specific swimming activity. Silver redhorse demonstrated progressive
increases in activity during upstream fishway passage. Moreover, location
specific passage duration decreased with an increasing number of passage
attempts. Turning basins and the most upstream basin were found to delay fish
passage. No relationship was found between basin-specific passage duration and
activity and the respective values from previous basins. The results demonstrate
that successful fishway passage requires periods of high activity. The resultant
energetic expenditure may affect fitness, foraging behaviour and increase
susceptibility to predation, compromising population sustainability. This study
highlights the need to understand the physiological mechanisms underpinning
fishway passage to improve future designs and interpretation of biological
evaluations.
PMID- 25853246
TI - Health service utilization for mental, behavioural and emotional problems among
conflict-affected population in Georgia: a cross-sectional study.
AB - BACKGROUND: There is large gap in mental illness treatment globally and
potentially especially so in war-affected populations. The study aim was to
examine health care utilization patterns for mental, behavioural and emotional
problems among the war-affected adult population in the Republic of Georgia.
METHODS: A cross-sectional household survey was conducted among 3600 adults
affected by 1990s and 2008 armed conflicts in Georgia. Service use was measured
for the last 12 months for any mental, emotional or behavioural problems. TSQ,
PHQ-9 and GAD-7 were used to measure current symptoms of PTSD, depression and
anxiety. Descriptive and regression analyses were used. RESULTS: Respondents were
predominantly female (65.0%), 35.8% were unemployed, and 56.0% covered by the
government insurance scheme. From the total sample, 30.5% had symptoms of at
least one current mental disorder. Among them, 39.0% sought care for mental
problems, while 33.1% expressed facing barriers to accessing care and so did not
seek care. General practitioners (29%) and neurologists (26%) were consulted by
the majority of those with a current mental disorder who accessed services, while
use of psychiatric services was far more limited. Pharmacotherapy was the
predominant type of care (90%). Female gender (OR 1.50, 95% CI: 1.25, 1.80),
middle-age (OR 1.83, 95% CI: 1.48, 2.26) and older-age (OR 1.62, 95% CI: 1.19,
2.21), possession of the state insurance coverage (OR 1.55, 95% CI: 1.30, 1.86),
current PTSD symptoms (OR 1.56, 95% CI: 1.29, 1.90) and depression (OR 2.12, 95%
CI: 1.70, 2.65) were associated with higher rates of health service utilization,
while employed were less likely to use services (OR 0.71, 95% CI: 0.55, 0.89).
CONCLUSIONS: Reducing financial access barriers and increasing awareness and
access to local care required to help reduce the burden of mental disorders among
conflict-affected persons in Georgia.
PMID- 25853248
TI - Correction: Hexon modification to improve the activity of oncolytic adenovirus
vectors against neoplastic and stromal cells in pancreatic cancer.
PMID- 25853247
TI - Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes
without retinopathy or microalbuminuria.
AB - OBJECTIVE: Corneal innervation is increasingly used as a surrogate marker of
human diabetic peripheral neuropathy (DPN) however its temporal relationship with
the other microvascular complications of diabetes is not fully established. In
this cross-sectional, observational study we aimed to assess whether neuropathy
occurred in patients with type 1 diabetes, without retinopathy or
microalbuminuria. MATERIALS AND METHODS: All participants underwent detailed
assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration
perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV),
sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal
microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria
status [albumin: creatinine ratio (ACR)]. RESULTS: 53 patients with Type 1
diabetes with (n=37) and without retinopathy (n=16) were compared to control
subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and
length (CNFL) were reduced significantly (p<0.001) in diabetic patients without
retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were
also significantly (p<0.001) reduced in diabetic patients without
microalbuminuria (n=39), compared to control subjects. Greater neuropathic
severity was associated with established retinopathy and microalbuminuria.
CONCLUSIONS: IVCCM detects early small fibre damage in the absence of retinopathy
or microalbuminuria in patients with Type 1 diabetes.
PMID- 25853250
TI - An observational study examining the relationship between respiratory symptoms,
airway inflammation and bacteriology in children with severe neurodisability.
AB - BACKGROUND: Children with severe neurodisability (ND) commonly suffer from
chronic respiratory symptoms that impact greatly on quality of life, and lead to
recurrent hospital admissions. This morbidity (and its causes) is poorly
described, despite being well recognised by paediatricians. In this study, we
characterised respiratory symptoms in children with ND at times of stability and
deterioration. We also assessed the relationship between respiratory symptoms,
lower airway inflammatory markers and levels of infection/colonisation. METHODS:
ND children were recruited upon admission for elective surgery (Elective-ND [n =
16]), or acutely upon admission to Intensive Care (PICU-ND [n = 19]), and
compared to healthy control children [n = 12]. Parents completed a validated
respiratory symptom questionnaire in which symptoms associated with activity were
removed (total maximal score of 108). Bronchoalveolar lavage (BAL) was collected,
and BAL neutrophil counts, IL-8 and TGFbeta-1 levels measured. BAL microbial
analysis was performed using a 16S/18S rRNA gene based assay and Pseudomonas
aeruginosa PCR. RESULTS: All ND children had high levels of respiratory symptoms
(median [IQR] symptom score PICU-ND, 55[38-64]; Elective-ND, 26[7-45]; Control,
4[0-7]: p<0.01), which affected their families, particularly at nighttime.
Elective-ND patients with a total respiratory symptom score >20 invariably had
BAL neutrophilia. Elective patients with 16S/18S microbial rDNA positive BAL had
higher neutrophil counts (positive, 33[18-70]%; negative, 8[4-38]%: p<0.05) and
generally higher symptom scores (positive, 17[5-32]; negative, 5[0-9]: p =
0.097). Streptococcus mitis was commonly identified in BAL from ND children;
Pseudomonas aeruginosa was not identified in any sample. CONCLUSIONS: Children
with severe ND often have high levels of chronic respiratory symptoms, which may
relate to lower airway inflammation. Bacterial airway colonisation, particularly
with oral commensals, may play a role in both symptom generation and
inflammation.
PMID- 25853251
TI - The palaeoenvironmental impact of prehistoric settlement and proto-historic
urbanism: tracing the emergence of the Oppidum of Corent, Auvergne, France.
AB - Early human societies and their interactions with the natural world have been
extensively explored in palaeoenvironmental studies across Central and Western
Europe. Yet, despite an extensive body of scholarship, there is little
consideration of the environmental impacts of proto-historic urbanisation.
Typically palaeoenvironmental studies of Bronze and Iron Age societies discuss
human impact in terms of woodland clearance, landscape openness and evidence for
agriculture. Although these features are clearly key indicators of human
settlement, and characterise Neolithic and early to Middle Bronze Age impacts at
Corent, they do not appear to represent defining features of a protohistoric
urban environment. The Late Iron Age Gallic Oppidum of Corent is remarkable for
the paucity of evidence for agriculture and strong representation of apophytes
associated with disturbance. Increased floristic diversity - a phenomenon also
observed in more recent urban environments - was also noted. The same, although
somewhat more pronounced, patterns are noted for the Late Bronze Age and hint at
the possibility of a nascent urban area. High percentages of pollen from non
native trees such as Platanus, Castanea and Juglans in the late Bronze Age and
Gallic period also suggest trade and cultural exchange, notably with the
Mediterranean world. Indeed, these findings question the validity of applying
Castanea and Juglans as absolute chronological markers of Romanisation. These
results clearly indicate the value of local-scale palaeoecological studies and
their potential for tracing the phases in the emergence of a proto-historic urban
environment.
PMID- 25853249
TI - Is that me or my twin? Lack of self-face recognition advantage in identical
twins.
AB - Despite the increasing interest in twin studies and the stunning amount of
research on face recognition, the ability of adult identical twins to
discriminate their own faces from those of their co-twins has been scarcely
investigated. One's own face is the most distinctive feature of the bodily self,
and people typically show a clear advantage in recognizing their own face even
more than other very familiar identities. Given the very high level of
resemblance of their faces, monozygotic twins represent a unique model for
exploring self-face processing. Herein we examined the ability of monozygotic
twins to distinguish their own face from the face of their co-twin and of a
highly familiar individual. Results show that twins equally recognize their own
face and their twin's face. This lack of self-face advantage was negatively
predicted by how much they felt physically similar to their co-twin and by their
anxious or avoidant attachment style. We speculate that in monozygotic twins, the
visual representation of the self-face overlaps with that of the co-twin. Thus,
to distinguish the self from the co-twin, monozygotic twins have to rely much
more than control participants on the multisensory integration processes upon
which the sense of bodily self is based. Moreover, in keeping with the notion
that attachment style influences perception of self and significant others, we
propose that the observed self/co-twin confusion may depend upon insecure
attachment.
PMID- 25853252
TI - Both fasting and glucose-stimulated proinsulin levels predict hyperglycemia and
incident type 2 diabetes: a population-based study of 9,396 Finnish men.
AB - BACKGROUND: Hyperproinsulinemia is an indicator of beta-cell dysfunction, and
fasting proinsulin levels are elevated in patients with hyperglycemia. It is not
known whether proinsulin levels after a glucose load are better predictors of
hyperglycemia and type 2 diabetes than fasting proinsulin. METHODS: Participants
were 9,396 Finnish men (mean+/-SD, age 57.3+/-7.1 years, BMI 27.0+/-4.0 kg/m2) of
the population-based METabolic Syndrome In Men Study who were non-diabetic at the
recruitment, and who participated in a 6-year follow-up study. Proinsulin and
insulin levels were measured in the fasting state and 30 and 120 min after an
oral glucose load. Area under the curve (AUC) and proinsulin to insulin ratios
were calculated. RESULTS: Fasting proinsulin, proinsulin at 30 min and proinsulin
AUC during the first 30 min of an oral glucose tolerance test significantly
predicted both the worsening of hyperglycemia and type 2 diabetes after
adjustment for confounding factors. Further adjustment for insulin sensitivity
(Matsuda index) or insulin secretion (Disposition index) weakened these
associations. Insulin sensitivity had a major impact on these associations.
CONCLUSION: Our results suggest that proinsulin in the fasting state and after an
oral glucose load similarly predict the worsening of hyperglycemia and conversion
to type 2 diabetes.
PMID- 25853253
TI - Features of the retinotopic representation in the visual wulst of a laterally
eyed bird, the zebra finch (Taeniopygia guttata).
AB - The visual wulst of the zebra finch comprises at least two retinotopic maps of
the contralateral eye. As yet, it is not known how much of the visual field is
represented in the wulst neuronal maps, how the organization of the maps is
related to the retinal architecture, and how information from the ipsilateral eye
is involved in the activation of the wulst. Here, we have used autofluorescent
flavoprotein imaging and classical anatomical methods to investigate such
characteristics of the most posterior map of the multiple retinotopic
representations. We found that the visual wulst can be activated by visual
stimuli from a large part of the visual field of the contralateral eye.
Horizontally, the visual field representation extended from -5 degrees beyond
the beak tip up to +125 degrees laterally. Vertically, a small strip from -10
degrees below to about +25 degrees above the horizon activated the visual
wulst. Although retinal ganglion cells had a much higher density around the fovea
and along a strip extending from the fovea towards the beak tip, these areas were
not overrepresented in the wulst map. The wulst area activated from the foveal
region of the ipsilateral eye, overlapped substantially with the middle of the
three contralaterally activated regions in the visual wulst, and partially with
the other two. Visual wulst activity evoked by stimulation of the frontal visual
field was stronger with contralateral than with binocular stimulation. This
confirms earlier electrophysiological studies indicating an inhibitory influence
of the activation of the ipsilateral eye on wulst activity elicited by
stimulating the contralateral eye. The lack of a foveal overrepresentation
suggests that identification of objects may not be the primary task of the zebra
finch visual wulst. Instead, this brain area may be involved in the processing of
visual information necessary for spatial orientation.
PMID- 25853254
TI - Molecular detection of Leishmania in phlebotomine sand flies (Diptera:
Psychodidae) from a cutaneous leishmaniasis focus atXakriaba Indigenous Reserve,
Brazil.
AB - Autochthonous cases of American cutaneous leishmaniasis (ACL) have been reported
since 2001 in the Xakriaba Indigenous Reserve located in the municipality of Sao
Joao das Missoes in northern Minas Gerais state, Brazil. In order to study the
presence of Leishmania DNA in phlebotomine sand flies, six entomological
collections were carried out from July 2008 through July 2009, using 40 light
traps placed in peridomicile areas of 20 randomly selected houses. From October
2011 through August 2012, another six collections were carried out with 20 light
traps distributed among four trails (five traps per trail) selected for a
previous study of wild and synanthropic hosts of Leishmania. A total of 4,760
phlebotomine specimens were collected belonging to ten genera and twenty-three
species. Single female specimens or pools with up to ten specimens of the same
locality, species and date, for Leishmania detection by molecular methods.
Species identification of parasites was performed with ITS1 PCR-RFLP using HaeIII
enzyme and genetic sequencing for SSU rRNA target. The presence of Leishmania DNA
was detected in eleven samples from peridomicile areas: Lu. longipalpis (two),
Nyssomyia intermedia (four), Lu. renei (two), Lu. ischnacantha, Micropygomyia
goiana and Evandromyia lenti (one pool of each specie). The presence of
Leishmania DNA was detected in twelve samples from among the trails: Martinsmyia
minasensis (six), Ny. intermedia (three), Mi. peresi (two) and Ev. lenti (one).
The presence of Leishmania infantum DNA in Lu. longipalpis and Leishmania
braziliensis DNA in Ny. intermediasupport the epidemiological importance of these
species of sand flies in the cycle of visceral and cutaneous leishmaniasis,
respectively. The results also found other species associated with Leishmania
DNA, such as Mt. minasensis and Ev. lenti, which may participate in a wild and/or
synanthropic cycle of Leishmania transmission in the studied area.
PMID- 25853255
TI - Ciprofloxacin-eluting nanofibers inhibits biofilm formation by Pseudomonas
aeruginosa and a methicillin-resistant Staphylococcus aureus.
AB - Pseudomonas aeruginosa and Staphylococcus aureus are commonly associated with
hospital-acquired infections and are known to form biofilms. Ciprofloxacin (CIP),
which is normally used to treat these infections, is seldom effective in killing
cells in a biofilm. This is mostly due to slow or weak penetration of CIP to the
core of biofilms. The problem is accentuated by the release of CIP below MIC
(minimal inhibitory concentration) levels following a rapid (burst) release. The
aim of this study was to develop a drug carrier that would keep CIP above MIC
levels for an extended period. Ciprofloxacin was suspended into poly(D,L-lactide)
(PDLLA) and poly(ethylene oxide) (PEO), and electrospun into nanofibers (CIP-F).
All of the CIP was released from the nanofibers within 2 h, which is typical of a
burst release. However, 99% of P. aeruginosa PA01 cells and 91% of S. aureus Xen
30 cells (a methicillin-resistant strain) in biofilms were killed when exposed to
CIP-F. CIP levels remained above MIC for 5 days, as shown by growth inhibition of
the cells in vitro. The nanofibers were smooth in texture with no bead formation,
as revealed by scanning electron and atomic force microscopy. A single vibration
peak at 1632 cm-1, recorded with Fourier transform infrared spectroscopy,
indicated that CIP remained in crystal form when incorporated into PDLLA: PEO. No
abnormalities in the histology of MCF-12A breast epithelial cells were observed
when exposed to CIP-F. This is the first report of the inhibition of biofilm
formation by CIP released from PDLLA: PEO nanofibers.
PMID- 25853256
TI - Informational needs and the quality of life of patients in their first year after
metastatic breast cancer diagnosis.
AB - BACKGROUND: Little is known about the informational needs and quality of life
(QOL) of patients with metastatic breast cancer (MBC) within the first year of
their diagnosis. OBJECTIVES: To describe the informational needs and QOL of
patients with MBC within the first year of diagnosis, and to identify
sociodemographic and medical factors that may be associated with informational
needs and QOL. METHODS: 52 patients (50 women, 2 men) enrolled within a year of
diagnosis of MBC completed a cross-sectional, self-administered paper survey that
included patient demographics, the Toronto Informational Needs Questionnaire
Breast Cancer (TINQ), the Hospital Anxiety and Depression Scale (HADS), and
Medical Outcomes Study Short Form-36 (SF-36). High informational need was defined
as a TINQ score of >= 200. RESULTS: Of the total 52 patients, 69% (35/52) had
high informational needs, 20% met the criteria for anxiety (HADS-Anxiety score,
>= 11), and 8% met the criteria for depression. SF-36 scores were lower in all 8
subscales compared with the general population. Multivariate analyses showed that
patients who were married or living as married (OR, 6.1; 95% CI, 1.4-28.9) and
patients with de novo MBC (OR, 2.8; 95% CI, 0.5-14.3) or a shorter disease-free
interval (DFI; < 5 years; OR, 24.2; 95% CI, 3.1-187.4) were more likely to have
more informational needs (C statistic, 0.824) than were patients with a longer
DFI (>= 5 years). LIMITATIONS: This is a small cross-sectional study of a single
academic institution. CONCLUSIONS: Patients with recently diagnosed MBC have high
informational needs and decreased overall QOL. Additional research and supportive
services meeting the informational and psychosocial needs of patients living with
MBC are warranted.
PMID- 25853257
TI - Weight change associated with third-generation adjuvant chemotherapy in breast
cancer patients.
AB - BACKGROUND: Studies have shown that breast cancer treatment can cause an increase
in weight. Weight gain during chemotherapy is usually significant and may be
associated with poor survival. However, the role of third- generation
chemotherapy regimens and weight gain is not well reviewed. METHODS: We
retrospectively analyzed the mean percentage weight change during the first year
after breast cancer diagnosis in 246 patients at West Virginia University during
September 2007 and October 2010. Kruskal-Wallis test and post hoc pairwise
comparisons were used to assess the influence of age, histology, stage,
ER/PR/HER2/neu status, menopausal status, and types of therapeutic modalities
received on the percentage weight change. Kaplan-Meier method with log-rank test
was used to evaluate recurrence-free survival (RFS). Local or distant recurrence
and disease progression were events for RFS analysis and disease-free patients
were censored at last follow-up. RESULTS: Mean weight gain was 0.39% (SD, 0.40)
of baseline body weight, 1 year after diagnosis of breast cancer. Premenopausal
status was the only factor associated with significant weight gain (+1.67% vs
0.10% for postmenopausal patients; P = .02). Stages >= III was associated with
significant weight loss (-1.64% for stages III, IV vs +0.85% for stages 0, I, II;
P = .02) and a lower RFS at 3 years and 5 years (P < .0001). Higher baseline
weight (> 90th percentile) did not have any significant impact on RFS (0.84 vs
0.91; P = .19). There was no significant change in weight relative to other
factors. CONCLUSIONS: Our study in patients receiving third-generation adjuvant
chemotherapy regimens did not show any significant change in percentage weight
with chemotherapy. Premenopausal status was the only significant factor
associated with weight gain. As expected, stage III or higher disease was
associated with significant weight loss and lower RFS.
PMID- 25853258
TI - Quality of supportive care for patients with advanced lung cancer in the Veterans
Health Administration.
AB - BACKGROUND: Morbidity related to cancer and its treatment remains a significant
source of human suffering and a challenge to the delivery of high-quality care.
OBJECTIVES: To develop and apply quality indicators to evaluate quality of
supportive care for advanced lung cancer in the Veterans Health Administration
(VHA) and examine facility-level predictors of quality. METHODS: We evaluated
supportive care quality using 12 quality indicators. Data were taken from VHA
electronic health records for incident lung cancer cases occurring during 2007.
Organizational characteristics of 111 VHA facilities were examined for
association with receipt of care. LIMITATIONS: Not all supportive care was
evaluated. Care processes identified as present at facilities may not have been
applied to cohort patients. Facility-level results may be influenced by errors in
attributing a patient's care to the correct facility. CONCLUSIONS: Quality
indicators for supportive cancer care can be developed and applied in large
evaluations using electronic health record review. This study confirmed high
quality supportive care, while identifying significant facility-level variation
in VHA.
PMID- 25853259
TI - Patient and provider concordance on symptoms during the oncology outpatient
clinic visit.
AB - BACKGROUND: Cancer patients experience multiple symptoms, with specific symptoms
varying by cancer type. Problems in communication between patients and health
care providers (HCPs) can interfere with effective symptom assessment and
management. OBJECTIVE: To address gaps in previous research by prospectively
examining concordance between HCPs and patients on identifying patients' symptoms
by using an identical tool for patients and HCPs at the time of the oncology
clinic visit. METHODS: 94 patients completed measures of symptom experience and
medical comorbidities before seeing their oncology medical team. HCPs were
informed of a patient's participation in the study before seeing the patient in
clinic. Immediately after the clinic visit, HCPs completed a symptom survey in
which they noted the patient's symptoms. RESULTS: Patients reported more symptoms
than the HCPs endorsed. The highest level of concordance for any symptom fell in
the moderate agreement range. Kappa values reflecting concordance between
patients and HCPs were not significantly different between the various patient
HCP pairs. No demographic or clinical variables for patients were found to be
statistically related to the level of agreement on patients' symptoms.
LIMITATIONS: The use of a small convenience sample size drawn from 3 specialty
oncology outpatient clinics may limit the generalizability of the results to
other types of cancer. The distribution of cancer stage was weighted toward
stages III and IV, likely contributing to the number of symptoms. CONCLUSIONS:
The level of agreement between HCPs and oncology patients on patient symptoms is
weak. Concordance levels were similar, regardless of the type of HCP.
PMID- 25853260
TI - Breast cancer with brain metastases in pregnancy.
AB - Breast cancer during pregnancy is a therapeutic challenge. Evidence to guide
management in metastatic breast cancer during pregnancy is limited, mainly
because of a lack of randomized trials. Care needs to be individualized with
interdisciplinary collaboration. Various case reports and case series in the
literature have shown the safety of some chemotherapeutic agents during the
second and third trimesters of pregnancy. Surgery is also safe after the first
trimester. Brain metastasis from breast cancer during pregnancy is an especially
challenging clinical situation and has been reported only in one other case. We
present the case of a young woman with HER2/neu overexpressed inflammatory breast
cancer who became pregnant while on treatment, refused termination of pregnancy,
and developed brain metastasis during the second trimester of pregnancy, posing a
management dilemma.
PMID- 25853261
TI - The WRKY transcription factor genes in eggplant (Solanum melongena L.) and Turkey
Berry (Solanum torvum Sw.).
AB - WRKY transcription factors, which play critical roles in stress responses, have
not been characterized in eggplant or its wild relative, turkey berry. The recent
availability of RNA-sequencing data provides the opportunity to examine WRKY
genes from a global perspective. We identified 50 and 62 WRKY genes in eggplant
(SmelWRKYs) and turkey berry (StorWRKYs), respectively, all of which could be
classified into three groups (I-III) based on the WRKY protein structure. The
SmelWRKYs and StorWRKYs contain ~76% and ~95% of the number of WRKYs found in
other sequenced asterid species, respectively. Positive selection analysis
revealed that different selection constraints could have affected the evolution
of these groups. Positively-selected sites were found in Groups IIc and III.
Branch-specific selection pressure analysis indicated that most WRKY domains from
SmelWRKYs and StorWRKYs are conserved and have evolved at low rates since their
divergence. Comparison to homologous WRKY genes in Arabidopsis revealed several
potential pathogen resistance-related SmelWRKYs and StorWRKYs, providing possible
candidate genetic resources for improving stress tolerance in eggplant and
probably other Solanaceae plants. To our knowledge, this is the first report of a
genome-wide analyses of the SmelWRKYs and StorWRKYs.
PMID- 25853263
TI - Serum selenium and ceruloplasmin in nigerians with peripartum cardiomyopathy.
AB - The study aimed to determine if selenium deficiency, serum ceruloplasmin and
traditional birth practices are risk factors for peripartum cardiomyopathy
(PPCM), in Kano, Nigeria. This is a case-control study carried out in three
hospitals, and PPCM patients were followed up for six months. Critically low
serum selenium concentration was defined as <70 ug/L. A total of 39 PPCM patients
and 50 controls were consecutively recruited after satisfying the inclusion
criteria. Mean serum selenium in patients (61.7 +/- 14.9 ug/L) was significantly
lower than in controls (118.4 +/- 45.6 ug/L) (p < 0.001). The prevalence of serum
selenium <70 ug/L was significantly higher among patients (76.9%) than controls
(22.0%) (p < 0.001). The mean ceruloplasmin and prevalence of socio-economic
indices, multiparity, pregnancy-induced hypertension, obesity and twin pregnancy
were not different between the groups (p > 0.05). Logistic regression showed that
rural residency significantly increased the odds for serum selenium <70 ug/L by
2.773-fold (p = 0.037). Baseline serum levels of selenium and ceruloplasmin were
not associated with six-month mortality. This study has shown that selenium
deficiency is a risk factor for PPCM in Kano, Nigeria, and is related to rural
residency. However, serum ceruloplasmin, customary birth practices and some other
characteristics were not associated with PPCM in the study area.
PMID- 25853262
TI - Phenotypic and molecular convergence of 2q23.1 deletion syndrome with other
neurodevelopmental syndromes associated with autism spectrum disorder.
AB - Roughly 20% of autism spectrum disorders (ASD) are syndromic with a well
established genetic cause. Studying the genes involved can provide insight into
the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative
gene, MBD5) is a recently identified genetic neurodevelopmental disorder
associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this
study, we provide a phenotypic update on the prevalent features of 2q23.1
deletion syndrome, which include severe intellectual disability, seizures,
significant speech impairment, sleep disturbance, and autistic-like behavioral
problems. Next, we examined the phenotypic, molecular, and network/pathway
relationships between nine neurodevelopmental disorders associated with ASD:
2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3
deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show
phenotypic overlaps consisting of intellectual disability, speech delay,
seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly,
MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1.
Network analysis reveals that there could be indirect protein interactions,
further implicating function for these genes in common pathways. Further, we show
that when MBD5 and RAI1 are haploinsufficient, they perturb several common
pathways that are linked to neuronal and behavioral development. These findings
support further investigations into the molecular and pathway relationships among
genes linked to neurodevelopmental disorders and ASD, which will hopefully lead
to common points of regulation that may be targeted toward therapeutic
intervention.
PMID- 25853264
TI - In Utero exposure to low-dose alcohol induces reprogramming of mammary
development and tumor risk in MMTV-erbB-2 transgenic mice.
AB - There is increasing evidence that prenatal exposure to environmental factors may
modify breast cancer risk later in life. This study aimed to investigate the
effects of in utero exposure to low-dose alcohol on mammary development and tumor
risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day
13 and day 19 of gestation, and the female offspring were examined for tumor
risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol
induced significant increases in ductal extension at 10 weeks of age. Molecular
analysis showed that in utero alcohol exposure induced upregulation of ERalpha
signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However,
enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10
week-old glands than did signaling in the other pathways. Interestingly, tumor
development in mice with in utero exposure to low-dose alcohol was slightly
delayed compared to control mice, but tumor multiplicity was increased. The
results indicate that in utero exposure to low-dose alcohol induces the
reprogramming of mammary development by mechanisms that include altered signaling
in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor
development pattern might be related to alcohol dose and exposure conditions, and
warrants further investigation.
PMID- 25853265
TI - Design of an osteoinductive extracellular fibronectin matrix protein for bone
tissue engineering.
AB - Integrin-mediated cell-matrix interactions play an important role in
osteogenesis. Here, we constructed a novel osteoinductive fibronectin matrix
protein (oFN) for bone tissue engineering, designed to combine the integrin
binding modules from fibronectin (iFN) and a strong osteoinductive growth factor,
bone morphogenetic protein-2. Compared with iFN, the purified oFN matrix protein
caused a significant increase in cell adhesion and osteogenic differentiation of
pre-osteoblast MC3T3-E1 cells (p < 0.05).
PMID- 25853266
TI - Interactive effects of dietary lipid and phenotypic feed efficiency on the
expression of nuclear and mitochondrial genes involved in the mitochondrial
electron transport chain in rainbow trout.
AB - A 2 * 3 factorial study was conducted to evaluate the effects of dietary lipid
level on the expression of mitochondrial and nuclear genes involved in electron
transport chain in all-female rainbow trout Oncorhynchus mykiss. Three practical
diets with a fixed crude protein content of 40%, formulated to contain 10%
(40/10), 20% (40/20) and 30% (40/30) dietary lipid, were fed to apparent satiety
to triplicate groups of either low-feed efficient (F120; 217.66 +/- 2.24 g
initial average mass) or high-feed efficient (F136; 205.47 +/- 1.27 g) full-sib
families of fish, twice per day, for 90 days. At the end of the experiment, the
results showed that there is an interactive effect of the dietary lipid levels
and the phenotypic feed efficiency (growth rate and feed efficiency) on the
expression of the mitochondrial genes nd1 (NADH dehydrogenase subunit 1), cytb
(Cytochrome b), cox1 (Cytochrome c oxidase subunits 1), cox2 (Cytochrome c
oxidase subunits 2) and atp6 (ATP synthase subunit 6) and nuclear genes ucp2alpha
(uncoupling proteins 2 alpha), ucp2beta (uncoupling proteins 2 beta), pparalpha
(peroxisome proliferator-activated receptor alpha), pparbeta (peroxisome
proliferatoractivated receptor beta) and ppargc1alpha (proliferator-activated
receptor gamma coactivator 1 alpha) in fish liver, intestine and muscle, except
on ppargc1alpha in the muscle which was affected by the diet and the family
separately. Also, the results revealed that the expression of mitochondrial genes
is associated with that of nuclear genes involved in electron transport chain in
fish liver, intestine and muscle. Furthermore, this work showed that the
expression of mitochondrial genes parallels with the expression of genes encoding
uncoupling proteins (UCP) in the liver and the intestine of rainbow trout. This
study for the first time presents the molecular basis of the effects of dietary
lipid level on mitochondrial and nuclear genes involved in mitochondrial electron
transport chain in fish.
PMID- 25853267
TI - Combined enzymatic and mechanical cell disruption and lipid extraction of green
alga Neochloris oleoabundans.
AB - Microalgal biodiesel is one of the most promising renewable fuels. The wet
technique for lipids extraction has advantages over the dry method, such as
energy-saving and shorter procedure. The cell disruption is a key factor in wet
oil extraction to facilitate the intracellular oil release. Ultrasonication, high
pressure homogenization, enzymatic hydrolysis and the combination of enzymatic
hydrolysis with high-pressure homogenization and ultrasonication were employed in
this study to disrupt the cells of the microalga Neochloris oleoabundans. The
cell disruption degree was investigated. The cell morphology before and after
disruption was assessed with scanning and transmission electron microscopy. The
energy requirements and the operation cost for wet cell disruption were also
estimated. The highest disruption degree, up to 95.41%, assessed by accounting
method was achieved by the combination of enzymatic hydrolysis and high-pressure
homogenization. A lipid recovery of 92.6% was also obtained by the combined
process. The combined process was found to be more efficient and economical
compared with the individual process.
PMID- 25853268
TI - [Position paper to the aut idem substitution obligation on inhalators].
PMID- 25853269
TI - [Aex - the area under the expiratory flow-volume loop].
AB - Preschool children often show total expiration times of less than one second in
pulmonary function tests. Therefore, FEV1 cannot be used for evaluation of
obstructive pulmonary diseases in small children. Aex, the area under the
expiratory flow-volume loop, does not depend on the expiration time. The Aex
value varies according to the convex or concave shape of the flow volume loop,
can be quantified and is a valuable parameter in the diagnosis of obstructive
airway diseases.In this study FEV1 und Aex values of 19882 flow-volume loops were
measured and compared. The comparison shows a very high correlation coefficient
of r = 0.99.The changes of both parameters in an individual after provocation or
bronchospasmolysis also demonstrate a strong correlation. A 20 % change of FEV1
equals an Aex change of 36 %.We conclude that measuring Aex is a good alternative
to measuring FEV1 especially if the FEV1 cannot be obtained due to short
expiration times.
PMID- 25853270
TI - [Angiogenin, bFGF and VEGF: angiogenic markers in breath condensate of patients
with pulmonary hypertension].
AB - Pulmonary arterial hypertension (PAH) is associated with a change in vascular
architecture. A characteristic histological feature is the plexiform lesion.
Similar alterations are observed in the pulmonary vascular bed of patients with
chronic thromboembolic pulmonary hypertension (CTEPH). Cytokines involved in
angiogenesis were found in both serum and lung tissue of patients with PAH and
CTEPH, although their role in the formation of plexiform lesions remains unclear.
The examination of breath condensate is a noninvasive technique to analyse
proteins possibly associated with the pathogenesis of various lung
diseases.Breath condensate of 22 patients with pulmonary hypertension (PAH: n =
12; CTEPH: n = 10) and 7 healthy volunteers was examined using a multiplex
fluorescent bead immunoassay to determine the concentrations of the biomarkers
angiogenin, bFGF, VEGF, IL-8, and TNF-alpha. Significantly higher levels of
angiogenin, bFGF and TNF-alpha were observed in breath condensate of patients
with pulmonary hypertension in comparison to healthy controls. Similarly, breath
condensate levels of VEGF were elevated in patients with PAH as against healthy
volunteers. However, IL-8 levels in breath condensate did not differ between the
two groups. The data suggest that breath condensate of patients with pulmonary
hypertension is characterized by increased levels of the angiogenic factors
angiogenin, VEGF and bFGF as well as TNF-alpha, but not IL-8. A larger study is
needed to confirm these results and to determine the prognostic and therapeutic
implications of these findings.
PMID- 25853271
TI - [Availability and integration of palliative medicine at certified lung cancer
centers].
AB - BACKGROUND: It is the aim of the certification system for Organ Cancer Centers of
the German Cancer Society to ensure that oncology patients receive therapy
meeting high quality standards. Lung cancer patients require comprehensive
palliative care due to their high symptom load. The purpose of the present study
was to identify the existing palliative care structures at 39 certified lung
cancer centers. METHODS: The survey tool used was an 18-question questionnaire
sent by surface mail to the respective centers. RESULTS: A total of 30 centers
took part in the survey. A physician with the additional qualification
'palliative care' was employed at 21 of the centers, a certified palliative care
nurse worked at 24 centers. A palliative care unit was available at 9 centers.
The cited obstacles to the delivery of palliative care included a shortage of
qualified palliative care staff, a lack of refinancing, and the concern that the
suggestion of palliative care might cause negative emotions in the respective
patients. CONCLUSIONS: Certified lung cancer centers had a wide range of
palliative care structures. Openness to and interest in extending existing
palliative care services were most commonly identified. A number of serious
obstacles in achieving this goal were nevertheless cited.
PMID- 25853274
TI - Charge-coupled substituted garnets (Y3-xCa0.5xM0.5x)Fe5O12 (M = Ce, Th):
structure and stability as crystalline nuclear waste forms.
AB - The garnet structure has been proposed as a potential crystalline nuclear waste
form for accommodation of actinide elements, especially uranium (U). In this
study, yttrium iron garnet (YIG) as a model garnet host was studied for the
incorporation of U analogs, cerium (Ce) and thorium (Th), incorporated by a
charge-coupled substitution with calcium (Ca) for yttrium (Y) in YIG, namely,
2Y(3+) = Ca(2+) + M(4+), where M(4+) = Ce(4+) or Th(4+). Single-phase garnets Y3
xCa0.5xM0.5xFe5O12 (x = 0.1-0.7) were synthesized by the citrate-nitrate
combustion method. Ce was confirmed to be tetravalent by X-ray absorption
spectroscopy and X-ray photoelectron spectroscopy. X-ray diffraction and (57)Fe
Mossbauer spectroscopy indicated that M(4+) and Ca(2+) cations are restricted to
the c site, and the local environments of both the tetrahedral and the octahedral
Fe(3+) are systematically affected by the extent of substitution. The charge
coupled substitution has advantages in incorporating Ce/Th and in stabilizing the
substituted phases compared to a single substitution strategy. Enthalpies of
formation of garnets were obtained by high temperature oxide melt solution
calorimetry, and the enthalpies of substitution of Ce and Th were determined. The
thermodynamic analysis demonstrates that the substituted garnets are entropically
rather than energetically stabilized. This suggests that such garnets may form
and persist in repositories at high temperature but might decompose near room
temperature.
PMID- 25853273
TI - Scalable synthesis of Fmoc-protected GalNAc-threonine amino acid and T(N) antigen
via nickel catalysis.
AB - The highly alpha-selective and scalable synthesis of the Fmoc-protected GalNAc
threonine amino acid and TN antigen in gram scale (0.5-1 g) is described. The
challenging 1,2-cis-2-amino glycosidic bond is addressed through a coupling of
threonine residues with C(2)-N-ortho-(trifluoromethyl)benzylidenamino
trihaloacetimidate donors mediated by Ni(4-F-PhCN)4(OTf)2. The desired 1,2-cis-2
amino glycoside was obtained in 66% yield (3.77 g) with alpha-only selectivity
and subsequently transformed into the Fmoc-protected GalNAc-threonine and TN
antigen. This operationally simple procedure no longer requires utilization of
the commonly used C(2)-azido donors and overcomes many of the limitations
associated with the synthesis of 1,2-cis linkage.
PMID- 25853275
TI - Gibbs excess and the calculation of the absolute surface composition of liquid
binary mixtures.
AB - Adsorption at the liquid-vapor interphase of a liquid binary mixture is
traditionally quantified by means of the Gibbs solute excess. Despite several
theoretical reviews on the meaning of Gibbs excess defined by the Gibbs dividing
surface, it is still misinterpreted as the excess concentration under
Guggenheim's finite-depth surface layer approach. In this work, both concepts are
clarified in a practical way, aided by a graphical representation without loss of
generality. The understanding of both quantities led to the development of a
thermodynamic procedure for the calculation of the actual number of solute and
solvent molecules at a finite-depth surface layer (not a monolayer), what is
called the absolute surface composition. From surface tension and density data,
the absolute surface composition of the binary aqueous mixtures of methanol,
ethanol, 1-propanol, and 1-butanol was calculated. Results show thermodynamic
consistency and agree with experimental reports and with an empirical mixing
rule. The increasing alcohol surface concentration throughout the entire
concentration range casts doubt on the formation of an alcohol monolayer, as was
suggested by other authors. Furthermore, the use of Guggenheim's monolayer model
does not reproduce the experimental data, nor does it show thermodynamic
consistency.
PMID- 25853276
TI - Combined Effects of Cadmium and UVB Radiation on Sea Urchin Embryos: Skeleton
Impairment Parallels p38 MAPK Activation and Stress Genes Overexpression.
AB - Human and natural activities release many pollutants in the marine environment.
The mixture of pollutants can affect many organisms concurrently. We used
Paracentrotus lividus as a model to analyze the effects on signal transduction
pathways and stress gene expression in embryos exposed continuously to double
stress, i.e., cadmium (Cd) from fertilization and UVB at cleavage (Cd/UVB
embryos). By microscopical inspection, we evaluated embryonic morphology after 72
h of development. Tissue-specific markers were used to assess mesoderm
differentiation by immunofluorescence. We analyzed p38MAPK, ERK1/2, and JNK
activation by Western blot and mRNA profiles of Pl-MT, Pl-14-3-3epsilon, and Pl
jun genes by real-time quantitative polymerase chain reaction (qPCR) and the
localization of their transcripts by whole mount in situ hybridization (WMISH).
We found that the Cd/UVB combined exposure induced morphological malformations in
76% of pluteus embryos, mainly affecting the development of the skeleton,
including the normal branching of skeletal roads. In Cd/UVB-embryos, p38MAPK was
activated 1 h after UVB exposure and a remarkable overexpression of the Pl-MT, Pl
14.3.3epsilon, and Pl-jun genes 24 h after UVB exposure. Pl-MT and Pl
14.3.3epsilon mRNAs were misexpressed as they were localized in a position
different from that observed in wild-type embryos, i.e., the intestine. On the
contrary, Pl-jun mRNA has remained localized in the skeletogenic cells despite
their displacement in exposed embryos. In conclusion, Cd/UVB exposure affected
skeletal patterning producing alternative morphologies in which p38MAPK
activation and Pl-MT, Pl-14.3.3epsilon, and Pl-jun gene overexpression seem
linked to a protective role against the stress response induced by Cd/UVB.
PMID- 25853277
TI - Improvement in PbS-based Hybrid Bulk-Heterojunction Solar Cells through Band
Alignment via Bismuth Doping in the Nanocrystals.
AB - We introduce dopants in lead sulfide (PbS) quantum dots (QDs) in forming hybrid
bulk-heterojunction (BHJ) solar cells. Because an increase in the content of
bismuth as dopants in PbS QDs transforms the intrinsic p-type semiconductor into
an n-type one, the band alignment between a conjugated polymer and the doped QDs
changes upon doping affecting performance of BHJ solar cells. From scanning
tunneling spectroscopy (STS) of the doped QDs, we observe a shift in their Fermi
energy leading to formation of a type II band alignment in the polymer:doped-QD
interface. We also show that the dopants improve electron-conduction process
through the QDs. With the dopants controlling both band alignments at the
interface and the conduction process, we show that the dopant concentration in
QDs influences open-circuit voltage unfavorably and short-circuit current in a
beneficial manner. The device performance of hybrid BHJ solar cells is hence
maximized at an optimum concentration of bismuth in PbS QDs.
PMID- 25853278
TI - Thermal activation of superheated lipid-coated perfluorocarbon drops.
AB - This study explored the thermal conditions necessary for the vaporization of
superheated perfluorocarbon nanodrops. Droplets C3F8 and C4F10 coated with a
homologous series of saturated diacylphosphatidylcholines were formed by
condensation of 4 MUm diameter microbubbles. These drops were stable at room
temperature and atmospheric pressure, but they vaporized back into microbubbles
at higher temperatures. The vaporization transition was measured as a function of
temperature by laser light extinction. We found that C3F8 and C4F10 drops
experienced 90% vaporization at 40 and 75 degrees C, respectively, near the
theoretical superheat limits (80-90% of the critical temperature). We therefore
conclude that the metastabilty of these phase-change agents arises not from the
droplet Laplace pressure altering the boiling point, as previously reported, but
from the metastability of the pure superheated fluid to homogeneous nucleation.
The rate of C4F10 drop vaporization was quantified at temperatures ranging from
55 to 75 degrees C, and an apparent activation energy barrier was calculated
from an Arrhenius plot. Interestingly, the activation energy increased linearly
with acyl chain length from C14 to C20, indicating that lipid interchain cohesion
plays an important role in suppressing the vaporization rate. The vaporized drops
(microbubbles) were found to be unstable to dissolution at high temperatures,
particularly for C14 and C16. However, proper choice of the fluorocarbon and
lipid species provided a nanoemulsion that could undergo at least ten reversible
condensation/vaporization cycles. The vaporization properties presented in this
study may facilitate the engineering of tunable phase-shift particles for
diagnostic imaging, targeted drug delivery, tissue ablation, and other
applications.
PMID- 25853279
TI - Superelastic and superhydrophobic nanofiber-assembled cellular aerogels for
effective separation of oil/water emulsions.
AB - Many applications proposed for functional nanofibers require their assembly into
a monolithic cellular structure. The ability to maintain structural integrity
upon large deformation is essential to ensure a macroscopic cellular material
that functions reliably. However, it remains a great challenge to achieve high
elasticity in three-dimensional (3D) nanofibrous networks. Here, we report a
strategy to create fibrous, isotropically bonded elastic reconstructed (FIBER)
aerogels with a hierarchical cellular structure and superelasticity by combining
electrospun nanofibers and the freeze-shaping technique. Our approach allows the
intrinsically lamellar deposited electrospun nanofibers to assemble into elastic
bulk aerogels with tunable porous structure and wettability on a large scale. The
resulting FIBER aerogels exhibit the integrated properties of ultralow density
(<30 mg cm(-3)), rapid recovery from 80% compression strain, superhydrophobic
superoleophilic wettability, and high pore tortuosity. More interestingly, the
FIBER aerogels can effectively separate surfactant-stabilized water-in-oil
emulsions, solely using gravity, with high flux (maximum of 8140 +/- 220 L m(-2)
h(-1)) and high separation efficiency, which match well with the requirements for
treating the real emulsions. The synthesis of FIBER aerogels also provides a
versatile platform for exploring the applications of nanofibers in a self
supporting, structurally adaptive, and 3D macroscopic form.
PMID- 25853280
TI - (68)Ga-labeled 3PRGD2 for dual PET and Cerenkov luminescence imaging of
orthotopic human glioblastoma.
AB - beta-Emitters can produce Cerenkov radiation that is detectable by Cerenkov
luminescence imaging (CLI), allowing the combination of PET and CLI with one
radiotracer for both tumor diagnosis and visual guidance during surgery.
Recently, the clinical feasibility of CLI with the established therapeutic
reagent Na(131)I and the PET tracer (18)F-FDG was demonstrated. (68)Ga possesses
a higher Cerenkov light output than (18)F and (131)I, which would result in
higher sensitivity for CLI and improve the outcome of CLI in clinical
applications. However, the research on (68)Ga-based tumor-specific tracers for
CLI is limited. In this study, we examined the use of (68)Ga-radiolabeled DOTA
3PRGD2 ((68)Ga-3PRGD2) for dual PET and CLI of orthotopic U87MG human
glioblastoma. For this purpose, the Cerenkov efficiencies of (68)Ga and (18)F
were measured with the IVIS Spectrum system (PerkinElmer, USA). The CLI signal
intensity of (68)Ga was 15 times stronger than that of (18)F. PET and CLI of
(68)Ga-3PRGD2 were performed in U87MG human glioblastoma xenografts. Both PET and
CLI revealed a remarkable accumulation of (68)Ga-3PRGD2 in the U87MG human
glioblastoma xenografts at 1 h p.i. with an extremely low background in the brain
when compared with (18)F-FDG. Furthermore, (68)Ga-3PRGD2 was used for dual PET
and CLI of orthotopic human glioblastoma. The orthotopic human glioblastoma was
clearly visualized by both imaging modalities. In addition, the biodistribution
of (68)Ga-3PRGD2 was assessed in normal mice to estimate the radiation dosimetry.
The whole-body effective dose is 20.1 +/- 3.3 MUSv/MBq, which is equal to 3.7 mSv
per whole-body PET scan with a 5 mCi injection dose. Thus, (68)Ga-3PRGD2 involves
less radiation exposure in patients when compared with (18)F-FDG (7.0 mSv). The
use of (68)Ga-3PRGD2 in dual PET and CLI shows great promise for tumor diagnosis
and image-guided surgery.
PMID- 25853282
TI - New bioinformatic tool for quick identification of functionally relevant
endogenous retroviral inserts in human genome.
AB - Endogenous retroviruses (ERVs) and LTR retrotransposons (LRs) occupy ~8% of human
genome. Deep sequencing technologies provide clues to understanding of functional
relevance of individual ERVs/LRs by enabling direct identification of
transcription factor binding sites (TFBS) and other landmarks of functional
genomic elements. Here, we performed the genome-wide identification of human
ERVs/LRs containing TFBS according to the ENCODE project. We created the first
interactive ERV/LRs database that groups the individual inserts according to
their familial nomenclature, number of mapped TFBS and divergence from their
consensus sequence. Information on any particular element can be easily extracted
by the user. We also created a genome browser tool, which enables quick mapping
of any ERV/LR insert according to genomic coordinates, known human genes and
TFBS. These tools can be used to easily explore functionally relevant individual
ERV/LRs, and for studying their impact on the regulation of human genes. Overall,
we identified ~110,000 ERV/LR genomic elements having TFBS. We propose a
hypothesis of "domestication" of ERV/LR TFBS by the genome milieu including
subsequent stages of initial epigenetic repression, partial functional release,
and further mutation-driven reshaping of TFBS in tight coevolution with the
enclosing genomic loci.
PMID- 25853283
TI - Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in
medication-free patients with major depressive disorder.
AB - BACKGROUND: Published meta-analyses of resting-state regional cerebral blood flow
(rCBF) studies of major depressive disorder (MDD) have included patients
receiving antidepressants, which might affect brain activity and thus bias the
results. To our knowledge, no meta-analysis has investigated regional homogeneity
changes in medication-free patients with MDD. Moreover, an association between
regional homogeneity and rCBF has been demonstrated in some brain regions in
healthy controls. We sought to explore to what extent resting-state rCBF and
regional homogeneity changes co-occur in the depressed brain without the
potential confound of medication. METHODS: Using the effect-size signed
differential mapping method, we conducted 2 meta-analyses of rCBF and regional
homogeneity studies of medication-free patients with MDD. RESULTS: Our systematic
search identified 14 rCBF studies and 9 regional homogeneity studies. We
identified conjoint decreases in resting-state rCBF and regional homogeneity in
the insula and superior temporal gyrus in medication-free patients with MDD
compared with controls. Other changes included altered resting-state rCBF in the
precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as
altered regional homogeneity in the uncus and parahippocampal gyrus. Meta
regression revealed that the percentage of female patients with MDD was
negatively associated with resting-state rCBF in the right anterior cingulate
cortex and that the age of patients with MDD was negatively associated with rCBF
in the left insula and with regional homogeneity in the left uncus. LIMITATIONS:
The analysis techniques, patient characteristics and clinical variables of the
included studies were heterogeneous. CONCLUSION: The conjoint alterations of rCBF
and regional homogeneity in the insula and superior temporal gyrus may be core
neuropathological changes in medication-free patients with MDD and serve as a
specific region of interest for further studies on MDD.
PMID- 25853286
TI - Assessing infertility-related stress: the factor structure of the Fertility
Problem Inventory in Italian couples undergoing infertility treatment.
AB - The factor structure of the Fertility Problem Inventory (FPI) and its invariance
across gender were examined in Italian couples undergoing infertility treatment.
About 1000 subjects (both partners of 500 couples) completed two questionnaires
prior to commencing infertility treatment at a private Clinic in Palermo, Italy.
Confirmatory Factor Analysis demonstrated that the original factor structure of
the FPI was partially confirmed. Two correlated factors (Infertility Life Domains
and Importance of Parenthood) were obtained via a post hoc Exploratory Factor
Analysis. Finally, the invariance of this factor structure across gender was
confirmed. The study supported the relevance of two interrelated factors specific
to infertility stress which could help clinicians to focus on the core
infertility-related stress domains of infertile couples.
PMID- 25853285
TI - Microstructural abnormalities of the brain white matter in attention
deficit/hyperactivity disorder.
AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an early-onset
neurodevelopmental disorder with multiple behavioural problems and executive
dysfunctions for which neuroimaging studies have reported a variety of
abnormalities, with inconsistencies partly owing to confounding by medication and
concurrent psychiatric disease. We aimed to investigate the microstructural
abnormalities of white matter in unmedicated children and adolescents with pure
ADHD and to explore the association between these abnormalities and behavioural
symptoms and executive functions. METHODS: We assessed children and adolescents
with ADHD and healthy controls using psychiatric interviews. Behavioural problems
were rated using the revised Conners' Parent Rating Scale, and executive
functions were measured using the Stroop Colour-Word Test and the Wisconsin Card
Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system,
and we compared diffusion parameters, including fractional anisotropy (FA) and
mean, axial and radial diffusivities, between the 2 groups. RESULTS: Thirty-three
children and adolescents with ADHD and 35 healthy controls were included in our
study. In patients compared with controls, FA was increased in the left posterior
cingulum bundle as a result of both increased axial diffusivity and decreased
radial diffusivity. In addition, the averaged FA of the cluster in this region
correlated with behavioural measures as well as executive function in patients
with ADHD. LIMITATIONS: This study was limited by its cross-sectional design and
small sample size. The cluster size of the significant result was small.
CONCLUSION: Our findings suggest that white matter abnormalities within the
limbic network could be part of the neural underpinning of behavioural problems
and executive dysfunction in patients with ADHD.
PMID- 25853284
TI - Using structural MRI to identify individuals at genetic risk for bipolar
disorders: a 2-cohort, machine learning study.
AB - BACKGROUND: Brain imaging is of limited diagnostic use in psychiatry owing to
clinical heterogeneity and low sensitivity/specificity of between-group
neuroimaging differences. Machine learning (ML) may better translate neuroimaging
to the level of individual participants. Studying unaffected offspring of parents
with bipolar disorders (BD) decreases clinical heterogeneity and thus increases
sensitivity for detection of biomarkers. The present study used ML to identify
individuals at genetic high risk (HR) for BD based on brain structure. METHODS:
We studied unaffected and affected relatives of BD probands recruited from 2
sites (Halifax, Canada, and Prague, Czech Republic). Each participant was
individually matched by age and sex to controls without personal or family
history of psychiatric disorders. We applied support vector machines (SVM) and
Gaussian process classifiers (GPC) to structural MRI. RESULTS: We included 45
unaffected and 36 affected relatives of BD probands matched by age and sex on an
individual basis to healthy controls. The SVM of white matter distinguished
unaffected HR from control participants (accuracy = 68.9%, p = 0.001), with
similar accuracy for the GPC (65.6%, p = 0.002) or when analyzing data from each
site separately. Differentiation of the more clinically heterogeneous affected
familiar group from healthy controls was less accurate (accuracy = 59.7%, p =
0.05). Machine learning applied to grey matter did not distinguish either the
unaffected HR or affected familial groups from controls. The regions that most
contributed to between-group discrimination included white matter of the
inferior/middle frontal gyrus, inferior/middle temporal gyrus and precuneus.
LIMITATIONS: Although we recruited 126 participants, ML benefits from even larger
samples. CONCLUSION: Machine learning applied to white but not grey matter
distinguished unaffected participants at high and low genetic risk for BD based
on regions previously implicated in the pathophysiology of BD.
PMID- 25853288
TI - The Influence of Interfaces on Properties of Thin-Film Inorganic Structural
Isomers Containing SnSe-NbSe2 Subunits.
AB - Inorganic isomers
([SnSe]1+delta)m(NbSe2)n([SnSe]1+delta)p(NbSe2)q([SnSe]1+delta)r(NbSe2)s where m,
n, p, q, r, and s are integers and m + p + r = n + q + s = 4 were prepared using
the modulated elemental reactant technique. This series of all six possible
isomers provides an opportunity to study the influence of interface density on
properties while maintaining the same unit cell size and composition. As
expected, all six compounds were observed to have the same atomic compositions
and an almost constant c-axis lattice parameter of ~4.90(5) nm, with a slight
trend in the c-axis lattice parameter correlated with the different number of
interfaces in the isomers: two, four and six. The structures of the constituents
in the ab-plane were independent of one another, confirming the nonepitaxial
relationship between them. The temperature dependent electrical resistivities
revealed metallic behavior for all the six compounds. Surprisingly, the
electrical resistivity at room temperature decreases with increasing number of
interfaces. Hall measurements suggest this results from changes in carrier
concentration, which increases with increasing thickness of the thickest SnSe
block in the isomer. Carrier mobility scales with the thickness of the thickest
NbSe2 block due to increased interfacial scattering as the NbSe2 blocks become
thinner. The observed behavior suggests that the two constituents serve different
purposes with respect to electrical transport. SnSe acts as a charge donor and
NbSe2 acts as the charge transport layer. This separation of function suggests
that such heterostructures can be designed to optimize performance through choice
of constituent, layer thickness, and layer sequence. A simplistic model, which
predicts the properties of the complex isomers from a weighted sum of the
properties of building blocks, was developed. A theoretical model is needed to
predict the optimal compound for specific properties among the many potential
compounds that can be prepared.
PMID- 25853287
TI - Antioxidant capacity and phenolic composition of leaves from 10 Bene (Pistacia
atlantica subsp. kurdica) genotypes.
AB - Leaves of 10 Bene genotypes were collected from six provinces (West Azerbaijan,
Kurdistan, Kermanshah, Ilam, Hamedan and Lorestan) in Iran. This study was
carried out to better characterise the total phenolic and flavonoid contents,
antioxidant capacity and phenolic composition, as well as to evaluate the
correlation between content of phenolic compounds and antioxidant activity in 10
genotypes of Bene. The antioxidant activity of leaf extracts was measured using
different assays: ferric reducing antioxidant power, nitric oxide radical
scavenging and 2,2-diphenyl-1-picrylhydrazyl. The results indicated that the
antioxidant capacity can be related to total phenolic and flavonoid content, so
that among all the genotypes studied here, the highest and the lowest phenolic
content and antioxidant activity were observed in B2 and B10 genotypes,
respectively. Analysing the phenolic composition using high performance liquid
chromatography, caffeic acid, vanillic acid, ferulic acid and sinapic acid were
found in all investigated genotypes.
PMID- 25853289
TI - Optical diagnosis of the progression and reversal of CCl4-induced liver injury in
rodent model using minimally invasive autofluorescence spectroscopy.
AB - Worldwide, liver cancer is the fifth most common cancer in men and seventh most
common cancer in women. Intoxicant-induced liver injury is one of the major
causes for severe structural damage with fibrosis and functional derangement of
the liver leading to cancer in its later stages. This report focuses on the
minimally invasive autofluorescence spectroscopic (AFS) studies on intoxicant,
carbon tetrachloride (CCl4)-induced liver damage in a rodent model. Different
stages of liver damage, including the reversed stage, on stoppage of the
intoxicant are examined. Emission from prominent fluorophores, such as collagen,
nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FAD),
and variations in redox ratio have been studied. A direct correlation between the
severity of the disease and the levels of collagen and redox ratio was observed.
On withdrawal of the intoxicant, a gradual reversal of the disease to normal
conditions was observed as indicated by the decrease in collagen levels and redox
ratio. Multivariate statistical techniques and principal component analysis
followed by linear discriminant analysis (PC-LDA) were used to develop diagnostic
algorithms for distinguishing different stages of the liver disease based on
spectral features. The PC-LDA modeling on a minimally invasive AFS dataset
yielded diagnostic sensitivities of 93%, 87% and 87% and specificities of 90%,
98% and 98% for pairwise classification among normal, fibrosis, cirrhosis and
reversal conditions. We conclude that AFS along with PC-LDA algorithm has the
potential for rapid and accurate minimally invasive diagnosis and detection of
structural changes due to liver injury resulting from various intoxicants.
PMID- 25853290
TI - Survival of Microencapsulated Probiotic Bacteria after Processing and during
Storage: A Review.
AB - The use of live probiotic bacteria as food supplement has become popular.
Capability of probiotic bacteria to be kept at room temperature becomes necessary
for customer's convenience and manufacturer's cost reduction. Hence, production
of dried form of probiotic bacteria is important. Two common drying methods
commonly used for microencapsulation are freeze drying and spray drying. In spite
of their benefits, both methods have adverse effects on cell membrane integrity
and protein structures resulting in decrease in bacterial viability.
Microencapsulation of probiotic bacteria has been a promising technology to
ensure bacterial stability during the drying process and to preserve their
viability during storage without significantly losing their functional properties
such acid tolerance, bile tolerance, surface hydrophobicity, and enzyme
activities. Storage at room temperatures instead of freezing or low temperature
storage is preferable for minimizing costs of handling, transportation, and
storage. Concepts of water activity and glass transition become important in
terms of determination of bacterial survival during the storage. The
effectiveness of microencapsulation is also affected by microcapsule materials.
Carbohydrate- and protein-based microencapsulants and their combination are
discussed in terms of their protecting effect on probiotic bacteria during
dehydration, during exposure to harsh gastrointestinal transit and small
intestine transit and during storage.
PMID- 25853291
TI - The effects of the frequency of the initial treatment with intravitreal
bevacizumab on macular volume and visual acuity.
AB - PURPOSE: The ideal notion of monthly intravitreal injections is difficult to
achieve when it comes to real-life scenarios. In reality, patients often are
treated with larger intervals due to circumstances. The purpose of this study was
to compare the results of intravitreal bevacizumab injections with shorter
intervals versus longer intervals for the treatment of choroidal
neovascularization (CNV) in age-related macular degeneration (AMD) in a real-life
clinic. METHODS: A retrospective, consecutive cohort study of naive eyes of
patients with CNV secondary to AMD treated with intravitreal bevacizumab.
Patients included underwent at least 3 consecutive injections with intervals <45
days in between them (Group A) or >45 days (Group B). Best corrected visual
acuity (BCVA) and optical coherence tomography were performed before the initial
intravitreal injections and after the last injection. RESULTS: Group A consisted
of 24 eyes of 18 patients and Group B 30 eyes of 25 patients. There was a
significantly larger mean of consecutive (5.0 vs. 3.78, P = 0.013) and total
(9.44 vs. 7.2, P = 0.021) injections in Group B. There was a significant
improvement in average BCVA in Group A only (0.65-0.52, P=0.006). However, a
significant and similar improvement in retinal volume was found in both groups (P
< 0.05). CONCLUSION: This study emphasizes the importance of achieving
consecutive injections with short intervals. Practitioners and decision makers
should be mindful that providing additional resources to accomplish proper
frequency may be more effective (visual outcome), cost effective (less
injections), and safer (less exposure) for the patient.
PMID- 25853292
TI - Classification of solid dispersions: correlation to (i) stability and solubility
(ii) preparation and characterization techniques.
AB - Solid dispersion has been a topic of interest in recent years for its potential
in improving oral bioavailability, especially for poorly water soluble drugs
where dissolution could be the rate-limiting step of oral absorption.
Understanding the physical state of the drug and polymers in solid dispersions is
essential as it influences both the stability and solubility of these systems.
This review emphasizes on the classification of solid dispersions based on the
physical states of drug and polymer. Based on this classification, stability
aspects such as crystallization tendency, glass transition temperature (Tg), drug
polymer miscibility, molecular mobility, etc. and solubility aspects have been
discussed. In addition, preparation and characterization methods for binary solid
dispersions based on the classification have also been discussed.
PMID- 25853293
TI - A dimensionless variable for the scale up and transfer of a roller compaction
formulation.
AB - Roller compaction is the most commonly employed dry granulation process in the
pharmaceutical industry. While this process is increasingly used as an
alternative to wet granulation, there are no parameter sets or system of
equations to quickly scale up or transfer a formulation between two pieces of
equipment. In this work, dimensionless variable was examined as a method to
transfer the operating parameters of a formulation between two different pieces
of equipment. This work was completed to establish the ground work for the
development of a dimensionless relationship relating the operating parameters of
the equipment to the porosity of the ribbon. The working hypothesis was three
fold, namely (i) that ribbons of the same porosity made with different equipment
will have similar properties, (ii) that it is possible to establish an objective
relationship between ribbon porosity and a combination of operating parameters
and raw material attributes and (iii) that by expressing such parameter
combination as a dimensionless variable, it will be possible to use the same
relationship for different pieces of roller compaction equipment. The
dimensionless variable RP/RS*HFS*True Density*D2 was found to correlate well with
the ribbon porosity for the formulations and equipment used in these experiments.
Depending on the formulation, the average difference in ribbon porosity between
the two units varied between 0.012 and 0.024.
PMID- 25853294
TI - Construction and in vitro/in vivo evaluation of 17-allylamino-17
demethoxygeldanamycin (17AAG)-loaded PEGylated nanostructured lipid carriers.
AB - In this study, the PEGylated nanostructured lipid carriers (PEG-NLC) were
constructed for the intravenous delivery of 17-allylamino-17
demethoxygeldanamycin (17AAG). 17AAG-PEG-NLC was successfully prepared by the
method of emulsion evaporation at a high temperature and solidification at a low
temperature using a mixture of glycerol monostearate and PEG2000-stearate as
solid lipids, and medium-chain triglyceride as the liquid lipid. The results
revealed that the morphology of the NLC was spheroidal. The particle size, zeta
potential and entrapment efficiency for 17AAG-PEG-NLC were observed as 189.4 nm,
20.2 mV and 83.42%, respectively. X-ray diffraction analysis revealed that 17AAG
existed as amorphous structures in the nanoparticles. In the in vitro release
study, the 17AAG from 17AAG-PEG-NLC exhibited a biphasic release pattern with
burst release initially and sustained release afterwards. In addition, 17AAG-PEG
NLC showed a significantly higher in vitro antitumor efficacy and longer
retention time in vivo than 17AAG solution. These results indicated that 17AAG
PEG-NLC may offer a promising alternative to the current 17AAG formulations for
the treatment of solid tumors.
PMID- 25853297
TI - Influence of emulsification process on the properties of Pickering emulsions
stabilized by layered double hydroxide particles.
AB - This paper reports the influence of emulsification process on the packing of
layered double hydroxide (LDH) particles at the aqueous/oil phase interface and
the properties of the resulting Pickering emulsions. Emulsions prepared by
ultrasonication display superior long-term stability and gel-like characteristics
at the dispersed phase volume fraction well below the random close packing limit,
whereas emulsions with same compositions prepared by vortex mixing show some
extent of sedimentation and liquid-like behaviors. Rheological measurements
demonstrate that the zero-shear elastic modulus and yield stress of gel-like
emulsions exhibit power-law dependences on particle concentration and
independence on aqueous/oil phase ratio. The microstructural origin of this
behavior is investigated by optical microscopy, revealing the droplets become
strongly adhesive and a heterogeneous percolating network is formed among
neighboring droplets. Fluorescent confocal microscopy measurements further
confirm that the droplet adhesion is due to particle layers bridging opposite
interfaces. In contrast, homogeneous, isolated, and densely packed droplets are
present in emulsions prepared by vortex mixing, which results in these systems
being dominantly viscous like the suspending fluid. This study shows that the
emulsification process can be used as a trigger to modify long-term stability and
rheology of solid-stabilized multiphase mixtures, which greatly expands their
potential technological applications.
PMID- 25853295
TI - Unraveling heterogeneous susceptibility and the evolution of breast cancer using
a systems biology approach.
AB - BACKGROUND: An essential question in cancer is why individuals with the same
disease have different clinical outcomes. Progress toward a more personalized
medicine in cancer patients requires taking into account the underlying
heterogeneity at different molecular levels. RESULTS: Here, we present a model in
which there are complex interactions at different cellular and systemic levels
that account for the heterogeneity of susceptibility to and evolution of ERBB2
positive breast cancers. Our model is based on our analyses of a cohort of mice
that are characterized by heterogeneous susceptibility to ERBB2-positive breast
cancers. Our analysis reveals that there are similarities between ERBB2 tumors in
humans and those of backcross mice at clinical, genomic, expression, and
signaling levels. We also show that mice that have tumors with intrinsically high
levels of active AKT and ERK are more resistant to tumor metastasis. Our findings
suggest for the first time that a site-specific phosphorylation at the serine 473
residue of AKT1 modifies the capacity for tumors to disseminate. Finally, we
present two predictive models that can explain the heterogeneous behavior of the
disease in the mouse population when we consider simultaneously certain genetic
markers, liver cell signaling and serum biomarkers that are identified before the
onset of the disease. CONCLUSIONS: Considering simultaneously tumor
pathophenotypes and several molecular levels, we show the heterogeneous behavior
of ERBB2-positive breast cancer in terms of disease progression. This and similar
studies should help to better understand disease variability in patient
populations.
PMID- 25853296
TI - PGC-1alpha activity in nigral dopamine neurons determines vulnerability to alpha
synuclein.
AB - INTRODUCTION: Mitochondrial dysfunction and oxidative stress are critical factors
in the pathogenesis of age-dependent neurodegenerative diseases. PGC-1alpha, a
master regulator of mitochondrial biogenesis and cellular antioxidant defense,
has emerged as a possible therapeutic target for Parkinson's disease, with
important roles in the function and survival of dopaminergic neurons in the
substantia nigra. The objective of this study is to determine if the loss of PGC
1alpha activity contributes to alpha-synuclein-induced degeneration. RESULTS: We
explore the vulnerability of PGC-1alpha null mice to the accumulation of human
alpha-synuclein in nigral neurons, and assess the neuroprotective effect of AAV
mediated PGC-1alpha expression in this experimental model. Using neuronal
cultures derived from these mice, mitochondrial respiration and production of
reactive oxygen species are assessed in conditions of human alpha-synuclein
overexpression. We find ultrastructural evidence for abnormal mitochondria and
fragmented endoplasmic reticulum in the nigral dopaminergic neurons of PGC-1alpha
null mice. Furthermore, PGC-1alpha null nigral neurons are more prone to
degenerate following overexpression of human alpha-synuclein, an effect more
apparent in male mice. PGC-1alpha overexpression restores mitochondrial
morphology, oxidative stress detoxification and basal respiration, which is
consistent with the observed neuroprotection against alpha-synuclein toxicity in
male PGC-1alpha null mice. CONCLUSIONS: Altogether, our results highlight an
important role for PGC-1alpha in controlling the mitochondrial function of nigral
neurons accumulating alpha-synuclein, which may be critical for gender-dependent
vulnerability to Parkinson's disease.
PMID- 25853298
TI - Aqueous Eu(II)-Containing Complex with Bright Yellow Luminescence.
AB - Eu(II)-containing materials have unique luminescence, redox, and magnetic
properties that have potential applications in optoelectronics, sensors, and
imaging. Here, we report the synthesis and characterization of Eu(II)-containing
aza-222 cryptate that displays yellow luminescence and a quantum yield of 26% in
aqueous media. The crystal structure reveals a staggered hula-hoop geometry. Both
solid-state and solution-phase data are presented that indicate that the high
quantum yield is a result of the absence of OH oscillators in the inner sphere of
the complex. We expect that Eu(II)-containing aza-222 cryptate is a step toward
Eu(II)-containing luminescent materials that can be used in a variety of
applications including biological imaging.
PMID- 25853299
TI - A de novo FOXP1 variant in a patient with autism, intellectual disability and
severe speech and language impairment.
AB - FOXP1 (forkhead box protein P1) is a transcription factor involved in the
development of several tissues, including the brain. An emerging phenotype of
patients with protein-disrupting FOXP1 variants includes global developmental
delay, intellectual disability and mild to severe speech/language deficits. We
report on a female child with a history of severe hypotonia, autism spectrum
disorder and mild intellectual disability with severe speech/language impairment.
Clinical exome sequencing identified a heterozygous de novo FOXP1 variant
c.1267_1268delGT (p.V423Hfs*37). Functional analyses using cellular models show
that the variant disrupts multiple aspects of FOXP1 activity, including
subcellular localization and transcriptional repression properties. Our findings
highlight the importance of performing functional characterization to help
uncover the biological significance of variants identified by genomics
approaches, thereby providing insight into pathways underlying complex
neurodevelopmental disorders. Moreover, our data support the hypothesis that de
novo variants represent significant causal factors in severe sporadic disorders
and extend the phenotype seen in individuals with FOXP1 haploinsufficiency.
PMID- 25853301
TI - Albumin: the next-generation delivery technology.
PMID- 25853302
TI - 'Close-to-ideal' tumor boron targeting for boron neutron capture therapy is
possible with 'less-than-ideal' boron carriers approved for use in humans.
PMID- 25853303
TI - The potential use of trigeminal nerve stimulation in the treatment of epilepsy.
PMID- 25853300
TI - PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3
microdeletion/microduplication syndrome.
AB - Array comparative genomic hybridization (aCGH) is a powerful genetic tool that
has enabled the identification of novel imbalances in individuals with
intellectual disability (ID), autistic disorders and congenital malformations.
Here we report a 'genotype first' approach using aCGH on 13 unrelated patients
with 19p13.3 submicroscopic rearrangement (11 deletions and 2 duplications) and
review cases in the literature and in public databases. Shared phenotypic
features suggest that these patients represent an interstitial
microdeletion/microduplication syndrome at 19p13.3. Common features consist of
abnormal head circumference in most patients (macrocephaly with the deletions and
microcephaly with the duplications), ID with developmental delay (DD), hypotonia,
speech delay and common dysmorphic features. The phenotype is associated with at
least a ~0.113 Mb critical region harboring three strong candidate genes probably
associated with DD, ID, speech delay and other dysmorphic features: MAP2K2,
ZBTB7A and PIAS4, an E3 ubiquitin ligase involved in the ubiquitin signaling
pathways, which we hypothesize for the first time to be associated with head size
in humans.
PMID- 25853305
TI - Subcutaneous formulation of tocilizumab for treatment of rheumatoid arthritis.
AB - Tocilizumab (TCZ) is a humanized monoclonal antibody against the IL-6 receptor
that is indicated for the treatment of rheumatoid arthritis (RA), juvenile
idiopathic arthritis and Castleman's disease. TCZ was developed as an intravenous
(IV) formulation and approved for RA treatment in Japan (2008), the EU (2009) and
the USA (2010). Recently, a subcutaneous (SC) formulation of TCZ was developed
and approved for RA treatment. Efficacy and safety of TCZ-SC were reported
through three randomized trials: MUSASHI, SUMMACTA and BREVACTA. Clinical
efficacy and overall safety of TCZ-SC was comparable to that of TCZ-IV. However
TCZ-SC, which is provided in a fixed dose, the efficacy was affected by patient
weight. The frequencies of injection site reactions and anti-TCZ antibodies were
increased with TCZ-SC compared with TCZ-IV, although differences were minimal and
at a negligible level for daily clinical practice. This review highlights the
potential of TCZ-SC in RA treatment.
PMID- 25853306
TI - Pulmonary delivery of anorectic oxyntomodulin in rats: food intake suppression,
reduced body weight gain and pharmacokinetics.
AB - BACKGROUND: Oxyntomodulin (OXM1-37) is an anorectic gut-secreting peptide with a
promise to treat obesity, but its needle-free delivery has yet to be successful.
RESULTS: Pulmonary delivery of OXM1-37, but not its C-terminal octapeptides,
caused dose-related, transient 4-6 h food intake suppression in rats. At 0.5
mg/kg, its 30-38% food intake suppression led to 46% reduction in body weight
gain by day 8. Its lung absorption was fast, elevating the systemic level
rapidly, yet the bioavailability was low at 13%. In the brain, twofold neuronal c
fos activation was seen in the hypothalamus arcuate nucleus and brainstem area
postrema. CONCLUSION: Pulmonary delivery is a promising needle-free systemic
delivery option for OXM1-37 to treat obesity, as enabling effective lung
absorption and brain interaction.
PMID- 25853307
TI - Gold nanoparticle-enhanced photodynamic therapy: effects of surface charge and
mitochondrial targeting.
AB - AIM: The authors aimed to further improve the efficiency and selectivity of gold
nanoparticle (Au NP)-assisted photodynamic therapy by modulating the surface
charge of Au NPs and delivering Au NPs particularly to mitochondria of breast
cancer cells. METHODS: Solid gold nanospheres (~50 nm) with negative and positive
surface charge were synthesized respectively, and mitochondria-targeting Au NPs
were prepared by conjugating with triphenylphosphonium molecules. CONCLUSION:
Positively charged Au NPs were preferably taken up by breast cancer cells.
Combination of positive surface charge with mitochondria-targeting domain onto Au
NPs allowed their accumulation in the mitochondria of breast cancer cells to
significantly elevate reactive oxygen species formation in 5-aminolevulinic-acid
enabled photodynamic therapy and improve selective destruction of breast cancer
cells.
PMID- 25853308
TI - miRNA therapy targeting cancer stem cells: a new paradigm for cancer treatment
and prevention of tumor recurrence.
AB - Cancer stem cells (CSCs) are a small subpopulation of cells within tumors that
retain the properties of self-renewal and tumorigenicity in vivo. Although CSCs
have been reported in multiple cancers, the regulation of CSCs has not been
described at the molecular level. miRNAs are endogenous small noncoding RNAs that
post-transcriptionally regulate the expression of their target genes via RNA
interference and are involved in almost all cellular processes. Since aberrant
miRNA expression occurs in CSCs, such dysregulated miRNAs may be promising
therapeutic targets. In this review, we summarize the current knowledge regarding
miRNAs that regulate CSC properties and discuss an in vivo delivery system for
synthetic miRNA mimics and miRNA inhibitors for the development of innovative
miRNA therapy against CSCs.
PMID- 25853309
TI - Theory and practice of supersaturatable formulations for poorly soluble drugs.
AB - Candidate compounds with high activity do not always possess adequate
physicochemical properties to be developed as commercial products. Notably, the
development of candidates with poor aqueous solubility has been a great challenge
in the past two decades. Formulations that offer supersaturated state during the
dissolution process are considered effective for increasing the oral
bioavailability of such candidates. Representative supersaturatable dosage forms
include amorphous solid dispersions, nanocrystal formulations and self
(micro)emulsifying drug delivery systems. This review describes the
characteristics of these formulations, with emphasis on the suitability of the
candidates for each type of formulation, from a physicochemical viewpoint.
Influence of developmental strategy on the formulation selection is also
discussed. This review aims to provide guidance for selecting formulations for
poorly soluble drugs based on both academic and practical backgrounds.
PMID- 25853311
TI - Macrophages as nanoparticle delivery vectors for photothermal therapy of brain
tumors.
AB - Certain types of stem and immune cells, which have an innate ability to target
and infiltrate tumors, can be utilized as vectors to deliver several types of
anticancer agents. In particular monocytes have the advantage of carrying
relatively large payloads of therapeutic nanomaterials, can be patient derived in
large numbers and are able to actively infiltrate tumors despite many barriers
often present in the microenvironment. Monocytes can selectively cross the
compromised blood-brain barrier surrounding brain tumors and are known to
actively migrate to hypoxic tumor regions. Of particular interest is the
observation that, following near-infrared exposure of tumors containing gold
nanoshell-loaded macrophages, sufficient hyperthermia can be generated to
suppress tumor growth. Collectively, these findings demonstrate the potential of
monocytes as nanoparticle delivery vectors for several types of site specific
light-based cancer therapies.
PMID- 25853310
TI - Delivery of local therapeutics to the brain: working toward advancing treatment
for malignant gliomas.
AB - Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are
characterized by their propensity to invade surrounding brain parenchyma, making
curative resection difficult. These tumors typically recur within two centimeters
of the resection cavity even after gross total removal. As a result, there has
been an emphasis on developing therapeutics aimed at achieving local disease
control. In this review, we will summarize the current developments in the
delivery of local therapeutics, namely direct injection, convection-enhanced
delivery and implantation of drug-loaded polymers, as well as the application of
these therapeutics in future methods including microchip drug delivery and local
gene therapy.
PMID- 25853313
TI - The general AMBER force field (GAFF) can accurately predict thermodynamic and
transport properties of many ionic liquids.
AB - We have applied molecular dynamics to calculate thermodynamic and transport
properties of a set of 19 room-temperature ionic liquids. Since accurately
simulating the thermophysical properties of solvents strongly depends upon the
force field of choice, we tested the accuracy of the general AMBER force field,
without refinement, for the case of ionic liquids. Electrostatic point charges
were developed using ab initio calculations and a charge scaling factor of 0.8 to
more accurately predict dynamic properties. The density, heat capacity, molar
enthalpy of vaporization, self-diffusivity, and shear viscosity of the ionic
liquids were computed and compared to experimentally available data, and good
agreement across a wide range of cation and anion types was observed. Results
show that, for a wide range of ionic liquids, the general AMBER force field, with
no tuning of parameters, can reproduce a variety of thermodynamic and transport
properties with similar accuracy to that of other published, often IL-specific,
force fields.
PMID- 25853312
TI - Potent and tumor specific: arming bacteria with therapeutic proteins.
AB - Bacteria are perfect vessels for targeted cancer therapy. Conventional
chemotherapy is limited by passive diffusion, and systemic administration causes
severe side effects. Bacteria can overcome these obstacles by delivering
therapeutic proteins specifically to tumors. Bacteria have been modified to
produce proteins that directly kill cells, induce apoptosis via signaling
pathways, and stimulate the immune system. These three modes of bacterial
treatment have all been shown to reduce tumor growth in animal models. Bacteria
have also been designed to convert nontoxic prodrugs to active therapeutic
compounds. The ease of genetic manipulation enables creation of arrays of
bacteria that release many new protein drugs. This versatility will allow
targeting of multiple cancer pathways and will establish a platform for
individualized cancer medicine.
PMID- 25853314
TI - Rates of chemical cleavage of DNA and RNA oligomers containing guanine oxidation
products.
AB - The nucleobase guanine in DNA (dG) and RNA (rG) has the lowest standard reduction
potential of the bases, rendering it a major site of oxidative damage in these
polymers. Mapping the sites at which oxidation occurs in an oligomer via chemical
reagents utilizes hot piperidine for cleaving oxidized DNA and aniline (pH 4.5)
for cleaving oxidized RNA. In the present studies, a series of time-dependent
cleavages of DNA and RNA strands containing various guanine lesions were examined
to determine the strand scission rate constants. The guanine base lesions 8-oxo
7,8-dihydroguanine (OG), spiroiminodihydantoin (Sp), 5-guanidinohydantoin (Gh),
2,2,4-triamino-2H-oxazol-5-one (Z), and 5-carboxamido-5-formamido-2
iminohydantoin (2Ih) were evaluated in piperidine-treated DNA and aniline-treated
RNA. These data identified wide variability in the chemical lability of the
lesions studied in both DNA and RNA. Further, the rate constants for cleaving
lesions in RNA were generally found to be significantly smaller than for lesions
in DNA. The OG nucleotides were poorly cleaved in DNA and RNA; Sp nucleotides
were slowly cleaved in DNA and did not cleave significantly in RNA; Gh and Z
nucleotides cleaved in both DNA and RNA at intermediate rates; and 2Ih
oligonucleotides cleaved relatively quickly in both DNA and RNA. The data are
compared and contrasted with respect to future experimental design.
PMID- 25853315
TI - Site-specific bioconjugation of an organometallic electron mediator to an enzyme
with retained photocatalytic cofactor regenerating capacity and enzymatic
activity.
AB - Photosynthesis consists of a series of reactions catalyzed by redox enzymes to
synthesize carbohydrates using solar energy. In order to take the advantage of
solar energy, many researchers have investigated artificial photosynthesis
systems mimicking the natural photosynthetic enzymatic redox reactions. These
redox reactions usually require cofactors, which due to their high cost become a
key issue when constructing an artificial photosynthesis system. Combining a
photosensitizer and an Rh-based electron mediator (RhM) has been shown to
photocatalytically regenerate cofactors. However, maintaining the high
concentration of cofactors available for efficient enzymatic reactions requires a
high concentration of the expensive RhM; making this process cost prohibitive. We
hypothesized that conjugation of an electron mediator to a redox enzyme will
reduce the amount of electron mediators necessary for efficient enzymatic
reactions. This is due to photocatalytically regenerated NAD(P)H being readily
available to a redox enzyme, when the local NAD(P)H concentration near the enzyme
becomes higher. However, conventional random conjugation of RhM to a redox enzyme
will likely lead to a substantial loss of cofactor regenerating capacity and
enzymatic activity. In order to avoid this issue, we investigated whether
bioconjugation of RhM to a permissive site of a redox enzyme retains cofactor
regenerating capacity and enzymatic activity. As a model system, a RhM was
conjugated to a redox enzyme, formate dehydrogenase obtained from Thiobacillus
sp. KNK65MA (TsFDH). A RhM-containing azide group was site-specifically
conjugated to p-azidophenylalanine introduced to a permissive site of TsFDH via a
bioorthogonal strain-promoted azide-alkyne cycloaddition and an appropriate
linker. The TsFDH-RhM conjugate exhibited retained cofactor regenerating capacity
and enzymatic activity.
PMID- 25853316
TI - Potential of Start Codon Targeted (SCoT) markers to estimate genetic diversity
and relationships among Chinese Elymus sibiricus accessions.
AB - Elymus sibiricus as an important forage grass and gene pool for improving cereal
crops, that is widely distributed in West and North China. Information on its
genetic diversity and relationships is limited but necessary for germplasm
collection, conservation and future breeding. Start Codon Targeted (SCoT) markers
were used for studying the genetic diversity and relationships among 53 E.
sibiricus accessions from its primary distribution area in China. A total of 173
bands were generated from 16 SCoT primers, 159 bands of which were polymorphic
with the percentage of polymorphic bands (PPB) of 91.91%. Based upon population
structure analysis five groups were formed. The cluster analysis separated the
accessions into two major clusters and three sub-clusters, similar to results of
principal coordinate analysis (PCoA). The molecular variance analysis (AMOVA)
showed that genetic variation was greater within geographical regions (50.99%)
than between them (49.01%). Furthermore, the study also suggested that collecting
and evaluating E. sibiricus germplasm for major geographic regions and special
environments broadens the available genetic base and illustrates the range of
variation. The results of the present study showed that SCoT markers were
efficient in assessing the genetic diversity among E. sibiricus accessions.
PMID- 25853317
TI - Organic-inorganic hybrid nanoparticles for bacterial inhibition: synthesis and
characterization of doped and undoped ONPs with Ag/Au NPs.
AB - Organic nanoparticles (ONPs) of lipoic acid and its doped derivatives ONPs/Ag and
ONPs/Au were prepared and characterized by UV-Visible, EDS, and TEM analysis. The
antibacterial properties of the ONPs ONPs/Ag and ONPs/Au were tested against
bacterial strains (Staphylococcus aureus, Bacillus cereus, Escherichia coli and
Salmonella typhi). Minimal Inhibitory Concentration (MIC) and bacterial growth
inhibition tests show that ONPs/Ag are more effective in limiting bacterial
growth than other NPs, particularly, for Gram positive than for Gram-negative
ones. The order of bacterial cell growth inhibition was ONPs/Ag > ONPs > ONPs/Au.
The morphology of the cell membrane for the treated bacteria was analyzed by SEM.
The nature of bond formation of LA with Ag or Au was analyzed by molecular
orbital and density of state (DOS) using DFT.
PMID- 25853319
TI - Ring-opening graft polymerization of propylene carbonate onto xylan in an ionic
liquid.
AB - The amidine organocatalyst 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is an
effective nucleophilic catalyst. Biocomposites with tuneable properties were
successfully synthesized by ring-opening graft polymerization (ROGP) of propylene
carbonate (PC) onto xylan using DBU as a catalyst in the ionic liquid (IL) 1
allyl-3-methylimidazolium chloride ([Amim]Cl). The effects of reaction
temperature, reaction time and the molar ratio of PC to anhydroxylose units (AXU)
in xylan were investigated. The physico-chemical properties of xylan-graft
poly(propylene carbonate) (xylan-g-PPC) copolymers were characterised by FT-IR,
NMR, TGA/DTG, AFM and tensile analysis. The FT-IR and NMR results indicated the
successful attachment of PPC onto xylan. TGA/DTG suggested the increased thermal
stability of xylan after the attachment of PPC side chains. AFM analysis revealed
details about the molecular aggregation of xylan-g-PPC films. The results also
showed that with the increased DS of xylan-g-PPC copolymers, the tensile strength
and Young's modulus of the films decreased, while the elongation at break
increased.
PMID- 25853318
TI - Nanocapsular dispersion of cinnamaldehyde for enhanced inhibitory activity
against aflatoxin production by Aspergillus flavus.
AB - Cinnamaldehyde (CA) is marginally soluble in water, making it challenging to
evenly disperse it in foods, and resulting in lowered anti-A. flavus efficacy. In
the present study, nano-dispersed CA (nano-CA) was prepared to increase its
aqueous solubility. Free and nano-dispersed CA were compared in terms of their
inhibitory activity against fungal growth and aflatoxin production of A. flavus
both in Sabouraud Dextrose (SD) culture and in peanut butter. Our results
indicated that free CA inhibited the mycelia growth and aflatoxin production of
A. flavus with a minimal inhibitory concentration (MIC) value of 1.0 mM, but
promoted the aflatoxin production at some concentrations lower than the MIC. Nano
CA had a lower MIC value of 0.8 mM against A. flavus, and also showed improved
activity against aflatoxin production without the promotion at lower dose. The
solidity of peanut butter had an adverse impact on the antifungal activity of
free CA, whereas nano-dispersed CA showed more than 2-fold improved activity
against the growth of A. flavus. Free CA still promoted AFB1 production at the
concentration of 0.25 mM, whereas nano-CA showed more efficient inhibition of
AFB1 production in the butter.
PMID- 25853320
TI - Two methods for increased specificity and sensitivity in loop-mediated isothermal
amplification.
AB - The technique of loop-mediated isothermal amplification (LAMP) utilizes four (or
six) primers targeting six (or eight) regions within a fairly small segment of a
genome for amplification, with concentration higher than that used in traditional
PCR methods. The high concentrations of primers used leads to an increased
likelihood of non-specific amplification induced by primer dimers. In this study,
a set of LAMP primers were designed targeting the prfA gene sequence of Listeria
monocytogenes, and dimethyl sulfoxide (DMSO) as well as Touchdown LAMP were
employed to increase the sensitivity and specificity of the LAMP reactions. The
results indicate that the detection limit of this novel LAMP assay with the newly
designed primers and additives was 10 fg per reaction, which is ten-fold more
sensitive than a commercial Isothermal Amplification Kit and hundred-fold more
sensitive than previously reported LAMP assays. This highly sensitive LAMP assay
has been shown to detect 11 strains of Listeria monocytogenes, and does not
detect other Listeria species (including Listeria innocua and Listeria
invanovii), providing some advantages in specificity over commercial Isothermal
Amplification Kits and previously reported LAMP assay.
PMID- 25853321
TI - Thermal Decomposition of NCN: Shock-Tube Study, Quantum Chemical Calculations,
and Master-Equation Modeling.
AB - The thermal decomposition of cyanonitrene, NCN, was studied behind reflected
shock waves in the temperature range 1790-2960 K at pressures near 1 and 4 bar.
Highly diluted mixtures of NCN3 in argon were shock-heated to produce NCN, and
concentration-time profiles of C atoms as reaction product were monitored with
atomic resonance absorption spectroscopy at 156.1 nm. Calibration was performed
with methane pyrolysis experiments. Rate coefficients for the reaction (3)NCN + M
-> (3)C + N2 + M (R1) were determined from the initial slopes of the C atom
concentration-time profiles. Reaction R1 was found to be in the low-pressure
regime at the conditions of the experiments. The temperature dependence of the
bimolecular rate coefficient can be expressed with the following Arrhenius
equation: k1(bim) = (4.2 +/- 2.1) * 10(14) exp[-242.3 kJ mol(-1)/(RT)] cm(3) mol(
1) s(-1). The rate coefficients were analyzed by using a master equation with
specific rate coefficients from RRKM theory. The necessary molecular data and
energies were calculated with quantum chemical methods up to the
CCSD(T)/CBS//CCSD/cc-pVTZ level of theory. From the topography of the potential
energy surface, it follows that reaction R1 proceeds via isomerization of NCN to
CNN and subsequent C-N bond fission along a collinear reaction coordinate without
a tight transition state. The calculations reproduce the magnitude and
temperature dependence of the rate coefficient and confirm that reaction R1 is in
the low-pressure regime under our experimental conditions.
PMID- 25853322
TI - From pair quadruple- to single-stranded helices to lines in a mixed ligand system
via adjusting the N-substituent of L-Glu.
AB - Utilizing the mixed-ligand strategy, a novel fourfold-interpenetrated 3D
homochiral metal-organic framework (1) with rare pair quadruple-stranded helices
was assembled from bpee (1,2-bis(4-pyridyl)ethylene) and NCG (N-carbamyl-l
glutamate). Changing the carbamyl substituent of NCG with benzoyl group (NBzG: N
benzoyl-l-glutamate), a non-interpenetrated 3D homochiral coordination polymer
(2) composed of alternate right-handed and left-handed single helix was obtained.
When p-tolylsulfonyl substituent was used instead, an interesting homochiral
linear structure (3) was formed from mixed-ligand bpee and NTsG (N-p
tolylsulfonyl-l-glutamate), with all individual NTsG being lined up orderly. The
steric hindrance of N-substituent of l-glu has a tremendous impact on the
construction of these diverse frameworks. Complexes 1-3 display second harmonic
generation (SHG) efficiencies, which are approximately 0.32, 0.45, and 0.55 times
as much as that of KDP powder.
PMID- 25853323
TI - [25 years after the Wall came down: psychiatry in East Germany revisited].
PMID- 25853324
TI - [The psychiatrist's white coat is outdated - pro].
PMID- 25853325
TI - [The psychiatrist's white coat is outdated - contra].
PMID- 25853326
TI - [Reports from the Federal Directors' Conference].
PMID- 25853327
TI - SNES: single nucleus exome sequencing.
AB - Single-cell genome sequencing methods are challenged by poor physical coverage
and high error rates, making it difficult to distinguish real biological variants
from technical artifacts. To address this problem, we developed a method called
SNES that combines flow-sorting of single G1/0 or G2/M nuclei, time-limited
multiple-displacement-amplification, exome capture, and next-generation
sequencing to generate high coverage (96%) data from single human cells. We
validated our method in a fibroblast cell line, and show low allelic dropout and
false-positive error rates, resulting in high detection efficiencies for single
nucleotide variants (92%) and indels (85%) in single cells.
PMID- 25853329
TI - Development and Application of alpha-Heteroatom Ketones in Asymmetric Michael
Reaction with beta-trans-Nitroalkenes.
AB - The successful design and application of a new type of N-phenyl-imidazole
modified alpha-heteroatom ketones in asymmetric anti-selective Michael reactions
with beta-trans-nitroalkenes is reported. High yields and enantioselectivities
could be obtained, and the corresponding conjugate adducts could be further
transformed into related chiral esters and cyclopropane derivatives with
excellent enantioselectivities.
PMID- 25853328
TI - Interaction of prion protein with acetylcholinesterase: potential pathobiological
implications in prion diseases.
AB - INTRODUCTION: The prion protein (PrP) binds to various molecular partners, but
little is known about their potential impact on the pathogenesis of prion
diseases RESULTS: Here, we show that PrP can interact in vitro with
acetylcholinesterase (AChE), a key protein of the cholinergic system in neural
and non-neural tissues. This heterologous association induced aggregation of
monomeric PrP and modified the structural properties of PrP amyloid fibrils.
Following its recruitment into PrP fibrils, AChE loses its enzymatic activity and
enhances PrP-mediated cytotoxicity. Using several truncated PrP variants and
specific tight-binding AChE inhibitors (AChEis), we then demonstrate that the PrP
AChE interaction requires two mutually exclusive sub-sites in PrP N-terminal
domain and an aromatic-rich region at the entrance of AChE active center gorge.
We show that AChEis that target this site impair PrP-AChE complex formation and
also limit the accumulation of pathological prion protein (PrPSc) in prion
infected cell cultures. Furthermore, reduction of AChE levels in prion-infected
heterozygous AChE knock-out mice leads to slightly but significantly prolonged
incubation time. Finally, we found that AChE levels were altered in prion
infected cells and tissues, suggesting that AChE might be directly associated
with abnormal PrP. CONCLUSION: Our results indicate that AChE deserves
consideration as a new actor in expanding pathologically relevant PrP morphotypes
and as a therapeutic target.
PMID- 25853330
TI - Functionalization of the PEG Corona of Nanoparticles by Clip Photochemistry in
Water: Application to the Grafting of RGD Ligands on PEGylated USPIO Imaging
Agent.
AB - The fast development of nanomedicines requires more and more reliable chemical
tools in order to accurately design materials and control the surface properties
of the nano-objects used in biomedical applications. In this study we describe a
smooth and simple photografting technique, i.e., the clip photochemistry, that
allows the introduction of molecules of interest in inert polymers or on stealth
nanoparticles directly in aqueous solution. First we developed the methodology on
polyethylene glycol (PEG) and looked for critical parameters of the process
(irradiation times, concentrations, washings) by using several molecular probes
and adapted analytical techniques ((19)F qNMR, EA, LSC). We found that the clip
photochemistry in water is a robust and efficient method to functionalize PEG.
Second we applied it on PEGylated USPIO (USPIO-PEG) magnetic resonance imaging
agent and succeeded in introducing RGD peptide and homemade peptidomimetics on
their PEG segments. The magnetic abilities of the conjugated nanoparticles were
unchanged by the derivatization process as evidenced by their relaxometric
properties and their NMRD profile. When tested on Jurkat lymphocyte T Cells,
which express alphavbeta3 integrins, the USPIO conjugated with RGD ligands leads
to an increase of the transverse relaxation rate (R2) by a factor 10 to 14 as
compared to USPIO-PEG. Consequently, it makes them good candidates for targeted
imaging technology in cancer therapy.
PMID- 25853331
TI - Ischemic brain injury in hemodialysis patients: which is more dangerous,
hypertension or intradialytic hypotension?
AB - Abnormalities of cognitive function and high levels of depression incidence are
characteristic of hemodialysis patients. Although previously attributed to the
humoral effects of uremia, it is becoming increasingly appreciated that many
elements of the overall disease state in CKD patients contribute to functional
disturbances and physical brain injury. These factors range from those associated
with the underlying primary diseases (cardiovascular, diabetes etc.) to those
specifically associated with the requirement for dialysis (including consequences
of the hemodialysis process itself). They are, however, predominantly ischemic
threats to the integrity of brain tissue. These evolving insights are starting to
allow nephrologists to appreciate the potential biological basis of dependency
and depression in our patients, as well as develop and test new therapeutic
approaches to this increasingly prevalent and important issue. This review aims
to summarize the current understanding of brain injury in this setting, as well
as examine recent advances being made in the modification of dialysis-associated
brain injury.
PMID- 25853332
TI - APOL1 toxin, innate immunity, and kidney injury.
AB - The discovery that two common APOL1 alleles were strongly associated with
nondiabetic kidney diseases in African descent populations led to hope for
improved diagnosis and treatment. Unfortunately, we still do not have a clear
understanding of the biological function played by APOL1 in podocytes or other
kidney cells, nor how the renal risk alleles initiate the development of
nephropathies. Important clues for APOL1 function may be gleaned from the natural
defense mechanism of APOL1 against trypanosome infections and from similar
proteins (e.g., diphtheria toxin, mammalian Bcl-2 family members). This review
provides an update on the biological functions for circulating (trypanosome
resistance) and intracellular (emerging role for autophagy) APOL1. Further, we
introduce a multimer model for APOL1 in kidney cells that reconciles the gain-of
function variants with the recessive inheritance pattern of APOL1 renal risk
alleles.
PMID- 25853333
TI - Phenotype standardization for drug-induced kidney disease.
AB - Drug-induced kidney disease is a frequent cause of renal dysfunction; however,
there are no standards to identify and characterize the spectrum of these
disorders. We convened a panel of international, adult and pediatric,
nephrologists and pharmacists to develop standardized phenotypes for drug-induced
kidney disease as part of the phenotype standardization project initiated by the
International Serious Adverse Events Consortium. We propose four phenotypes of
drug-induced kidney disease based on clinical presentation: acute kidney injury,
glomerular, tubular, and nephrolithiasis, along with the primary and secondary
clinical criteria to support the phenotype definition, and a time course based on
the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease, and
chronic kidney disease. Establishing causality in drug-induced kidney disease is
challenging and requires knowledge of the biological plausibility for the
specific drug, mechanism of injury, time course, and assessment of competing risk
factors. These phenotypes provide a consistent framework for clinicians,
investigators, industry, and regulatory agencies to evaluate drug nephrotoxicity
across various settings. We believe that this is the first step to recognizing
drug-induced kidney disease and developing strategies to prevent and manage this
condition.
PMID- 25853334
TI - Common histological patterns in glomerular epithelial cells in secondary focal
segmental glomerulosclerosis.
AB - Parietal epithelial cells (PECs) are involved in the development of sclerotic
lesions in primary focal and segmental glomerulosclerosis (FSGS). Here, the role
of PECs was explored in the more common secondary FSGS lesions in 68 patient
biopsies, diagnosed with 11 different frequently or rarely encountered glomerular
pathologies and additional secondary FSGS lesions. For each biopsy, one section
was quadruple stained for PECs (ANXA3), podocytes (synaptopodin), PEC matrix
(LKIV69), and Hoechst (nuclei), and a second was quadruple stained for activated
PECs (CD44 and cytokeratin-19), PEC matrix, and nuclei. In all lesions, cellular
adhesions (synechiae) between Bowman's capsule and the tuft were formed by cells
expressing podocyte and/or PEC markers. Cells expressing PEC markers were
detected in all FSGS lesions independent of the underlying glomerular disease and
often stained positive for markers of activation. Small FSGS lesions, which were
hardly identified on PAS sections previously, were detectable by
immunofluorescent staining using PEC markers, potentially improving the
diagnostic sensitivity to identify these lesions. Thus, similar patterns of cells
expressing podocyte and/or PEC markers were found in the formation of secondary
FSGS lesions independent of the underlying glomerular disease. Hence, our
findings support the hypothesis that FSGS lesions follow a final cellular pathway
to nephron loss that includes involvement of cells expressing PEC markers.
PMID- 25853336
TI - Biotin-triggered decomposable immunomagnetic beads for capture and release of
circulating tumor cells.
AB - Isolation of rare, pure, and viable circulating tumor cells (CTCs) provides a
significant insight in early cancer diagnosis, and release of captured CTCs
without damage for ex vivo culture may offer an opportunity for personalized
cancer therapy. In this work, we described a biotin-triggered decomposable
immunomagnetic system, in which peptide-tagged antibody designed by chemical
conjugation was specifically immobilized on engineered protein-coated magnetic
beads. The interaction between peptide and engineered protein can be reversibly
destroyed by biotin treatment, making capture and release of CTCs possible.
Furthermore, the peptide could mediate multiple antibodies' coimmobilization on
engineered protein-coated magnetic beads, by which capture efficiency for CTCs
was obviously improved. Quantitative results showed that 70% of captured cells
could be released by biotin addition, and 85% of released cells remained viable.
In addition, 79% of cancer cells spiked in human whole blood were captured and
could also be successfully released for culture. Finally, immunomagnetic beads
simultaneously loaded with anti-EpCAM, anti-HER2, and anti-EGFR were successfully
applied to isolate and detect CTCs in 17 cancer patients' peripheral blood
samples, and 2-215 CTCs were identified with high purity. These results suggest
that our method is reliable and has great potential in CTC detection for CTC
based molecular profiling, diagnosis, and therapy.
PMID- 25853335
TI - Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may
influence allograft survival in kidney transplantation.
AB - Variants in donor multidrug resistance protein 1 (ABCB1) and caveolin 1 (CAV1)
genes are associated with renal allograft failure after transplantation in
Europeans. Here we assessed transplantation outcomes of kidneys from 368 African
American (AA) and 314 European American (EA) deceased donors based on 38 single
nucleotide polymorphisms (SNPs) spanning ABCB1 and 16 SNPs spanning CAV1,
including previously associated index and haplotype-tagging SNPs. Tests for
association with time to allograft failure were performed for the 1233 resultant
kidney transplantations, adjusting for recipient age, sex, ethnicity, cold
ischemia time, panel reactive antibody, human leukocyte antigen match, expanded
criteria donation, and APOL1-nephropathy variants in AA donors. Interaction
analyses between APOL1 with ABCB1 and CAV1 were performed. In a meta-analysis of
all transplantations, ABCB1 index SNP rs1045642 was associated with time to
allograft failure and other ABCB1 SNPs were nominally associated, but not CAV1
SNPs. ABCB1 SNP rs1045642 showed consistent effects with the 558 transplantations
from EA donors, but not with the 675 transplantations from AA donors. ABCB1 SNP
rs956825 and CAV1 SNP rs6466583 interacted with APOL1 in transplants from AA
donors. Thus, the T allele at ABCB1 rs1045642 is associated with shorter renal
allograft survival for kidneys from American donors. Interactions between ABCB1
and CAV1 with APOL1 may influence allograft failure for transplanted kidneys from
AA donors.
PMID- 25853338
TI - Treatment of Collagen-Induced Arthritis Using Immune Modulatory Properties of
Human Mesenchymal Stem Cells.
AB - Mesenchymal stem cells (MSCs) have immune modulatory properties. We investigated
the potential therapeutic effects of human bone marrow (BM)-, adipose tissue (AD)
, and cord blood (CB)-derived MSCs in an experimental animal model of rheumatoid
arthritis (RA) and explored the mechanism underlying immune modulation by MSCs.
We evaluated the therapeutic effect of clinically available human BM-, AD-, and
CB-derived MSCs in DBA/1 mice with collagen-induced arthritis (CIA). CIA mice
were injected intraperitoneally with three types of MSCs. Treatment control
animals were injected with 35 mg/kg methotrexate (MTX) twice weekly. Clinical
activity in CIA mice, degree of inflammation, cytokine expression in the joint,
serum cytokine levels, and regulatory T cells (Tregs) were evaluated. Mice
treated with human BM-, AD-, and CB-MSCs showed significant improvement in
clinical joint score, comparable to MTX-treated mice. Histologic examination
showed greatly reduced joint inflammation and damage in MSC-treated mice compared
with untreated mice. Microcomputed tomography also showed little joint damage in
the MSC-treated group. MSCs significantly decreased serum interleukin (IL)-1beta,
tumor necrosis factor (TNF)-alpha, IL-6, and interferon-gamma and increased IL-10
and transforming growth factor-beta levels. Tregs were increased in mice treated
with MSCs compared to untreated or MTX-treated mice. Human BM-, AD-, and CB-MSCs
significantly suppressed joint inflammation in CIA mice. The cells decreased
proinflammatory cytokines and upregulated anti-inflammatory cytokines and induced
Tregs. Therefore, our study suggests that the use of human BM-, AD-, and CB-MSCs
could be an effective therapeutic approach for RA.
PMID- 25853337
TI - Macroscopic and macromolecular specificity of alkylphenol anesthetics for
neuronal substrates.
AB - We used a photoactive general anesthetic called meta-azi-propofol (AziPm) to test
the selectivity and specificity of alkylphenol anesthetic binding in mammalian
brain. Photolabeling of rat brain sections with [(3)H]AziPm revealed widespread
but heterogeneous ligand distribution, with [(3)H]AziPm preferentially binding to
synapse-dense areas compared to areas composed largely of cell bodies or myelin.
With [(3)H]AziPm and propofol, we determined that alkylphenol general anesthetics
bind selectively and specifically to multiple synaptic protein targets. In
contrast, the alkylphenol anesthetics do not bind to specific sites on abundant
phospholipids or cholesterol, although [(3)H]AziPm shows selectivity for
photolabeling phosphatidylethanolamines. Together, our experiments suggest that
alkylphenol anesthetic substrates are widespread in number and distribution,
similar to those of volatile general anesthetics, and that multi-target
mechanisms likely underlie their pharmacology.
PMID- 25853339
TI - Diacerein niosomal gel for topical delivery: development, in vitro and in vivo
assessment.
AB - The purpose of this study was to load diacerein (DCR) in niosomes by applying
response surface methodology and incorporate these niosomes in gel base for
topical delivery. Box-Behnken design was used to investigate the effect of charge
inducing agent (X1), surfactant HLB (X2) and sonication time (X3) on the vesicle
size (Y1), entrapment efficiency (Y2) and cumulative drug released (Y3). DCR
niosomal formulations were prepared by thin film hydration method. The optimized
formula was incorporated in different gel bases. DCR niosomal gels were evaluated
for homogeneity, rheological behavior; in vitro release and pharmacodynamic
activity by carrageenan-induced hind paw edema method in the rat compared with
DCR commercial gel. The results revealed that the mean vesicle sizes of the
prepared niosomes ranged from 7.33 to 23.72 um and the entrapment efficiency
ranged from 9.52% to 58.43% with controlled release pattern over 8 h. DCR
niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The
pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant,
37.66%, maximum inhibition of edema size in comparison with 20.83% for the
commercial gel (p < 0.05). These results recommended the incorporation of DCR
niosomes in 3% HPMC for topical application as a potent anti-inflammatory drug
for the treatment of osteoarthritis.
PMID- 25853340
TI - PEGylated liposomes of anastrozole for long-term treatment of breast cancer: in
vitro and in vivo evaluation.
AB - The aim of present study was to develop conventional and PEGylated (long
circulating), liposomes containing anastrozole (ANS) for effective treatment of
breast cancer. ANS is a third-generation non-steroidal aromatase inhibitor of the
triazole class used for the treatment of advanced and late-stage breast cancer in
post-menopausal women. Under such disease conditions the median duration of
therapy should be prolonged until tumor regression ends (>31 months). Liposomes
were prepared by the thin film hydration method by using ANS and various lipids
such as soyaphosphatidyl choline, cholesterol and methoxy polyethylene glycol
distearoyl ethanolamine in different concentration ratios and evaluated for
physical characteristics, in vitro drug release and stability. Optimized
formulations of liposome were studied for in vitro cytotoxic activity against the
BT-549 and MCF-7 cell lines and in vivo behavior in Wistar rats. Preformulation
studies, both Fourier transform infrared study and differential scanning
calorimetry analysis showed no interaction between the drug and the excipients
used in the formulations. The optimized formulations AL-07 and AL-09 liposomes
showed encapsulation efficiencies in the range 65.12 +/- 1.05% to 69.85 +/- 3.2%
with desired mean particle size distribution of 101.1 +/- 5.9 and 120.2 +/- 2.8
nm and zeta potentials of -43.7 +/- 4.7 and -62.9 +/- 3.5 mV. All the optimized
formulations followed Higuchi-matrix release kinetics and when plotted in
accordance with the Korsemeyer-Peppas method, the n-value 0.5 < n < 1.0 suggests
an anomalous (non-Fickian) transport. Likewise, the PEGylated liposomes showed
greater tumor growth inhibition on BT-549 and MCF-7 cell lines from in vitro
cytotoxicity studies (p < 0.05). Pharmacokinetic study of conventional and
PEGylated liposomes in Wistar rats demonstrated a 3.33- and 20.28-fold increase
in AUC(0-infinity) values when compared to pure drug (p < 0.001). Among the
formulations, PEGylated liposomes showed encouraging results by way of their long
circulation and sustained delivery properties for effective treatment of breast
cancer.
PMID- 25853341
TI - Study of permeation and blocker binding in TMEM16A calcium-activated chloride
channels.
AB - We studied the effects of mutations of positively charged amino acid residues in
the pore of X. tropicalis TMEM16A calcium-activated chloride channels: K613E,
K628E, K630E; R646E and R761E. The activation and deactivation kinetics were not
affected, and only K613E showed a lower current density. K628E and R761E affect
anion selectivity without affecting Na(+) permeation, whereas K613E, R646E and
the double mutant K613E + R646E affect anion selectivity and permeability to
Na(+). Furthermore, altered blockade by the chloride channel blockers anthracene
9-carboxylic acid (A-9-C), 4, 4'-Diisothiocyano-2,2'-stilbenedisulfonic acid
(DIDS) and T16inh-A01 was observed. These results suggest the existence of 2
binding sites for anions within the pore at electrical distances of 0.3 and 0.5.
These sites are also relevant for anion permeation and blockade.
PMID- 25853342
TI - Using a sequential regimen to eliminate bacteria at sublethal antibiotic dosages.
AB - We need to find ways of enhancing the potency of existing antibiotics, and, with
this in mind, we begin with an unusual question: how low can antibiotic dosages
be and yet bacterial clearance still be observed? Seeking to optimise the
simultaneous use of two antibiotics, we use the minimal dose at which clearance
is observed in an in vitro experimental model of antibiotic treatment as a
criterion to distinguish the best and worst treatments of a bacterium,
Escherichia coli. Our aim is to compare a combination treatment consisting of two
synergistic antibiotics to so-called sequential treatments in which the choice of
antibiotic to administer can change with each round of treatment. Using
mathematical predictions validated by the E. coli treatment model, we show that
clearance of the bacterium can be achieved using sequential treatments at
antibiotic dosages so low that the equivalent two-drug combination treatments are
ineffective. Seeking to treat the bacterium in testing circumstances, we
purposefully study an E. coli strain that has a multidrug pump encoded in its
chromosome that effluxes both antibiotics. Genomic amplifications that increase
the number of pumps expressed per cell can cause the failure of high-dose
combination treatments, yet, as we show, sequentially treated populations can
still collapse. However, dual resistance due to the pump means that the
antibiotics must be carefully deployed and not all sublethal sequential
treatments succeed. A screen of 136 96-h-long sequential treatments determined
five of these that could clear the bacterium at sublethal dosages in all
replicate populations, even though none had done so by 24 h. These successes can
be attributed to a collateral sensitivity whereby cross-resistance due to the
duplicated pump proves insufficient to stop a reduction in E. coli growth rate
following drug exchanges, a reduction that proves large enough for appropriately
chosen drug switches to clear the bacterium.
PMID- 25853344
TI - An end to the culture of silence in the NHS: the Francis review.
PMID- 25853345
TI - Calling time on the Cancer Drugs Fund? Funding the NHS in the age of austerity.
PMID- 25853346
TI - The Five year forward view: issues of funding and the ageing population still
need addressing.
PMID- 25853347
TI - A clinician's guide to cardiopulmonary exercise testing 1: an introduction.
AB - Compared to standard exercise tolerance testing, cardiopulmonary exercise testing
is a reliable and powerful tool that can be used for risk stratification,
exercise prescription and clinical diagnosis.
PMID- 25853343
TI - Cytosolic Hsp70 and co-chaperones constitute a novel system for tRNA import into
the nucleus.
AB - tRNAs are unique among various RNAs in that they shuttle between the nucleus and
the cytoplasm, and their localization is regulated by nutrient conditions.
Although nuclear export of tRNAs has been well documented, the import machinery
is poorly understood. Here, we identified Ssa2p, a major cytoplasmic Hsp70 in
Saccharomyces cerevisiae, as a tRNA-binding protein whose deletion compromises
nuclear accumulation of tRNAs upon nutrient starvation. Ssa2p recognizes several
structural features of tRNAs through its nucleotide-binding domain, but prefers
loosely-folded tRNAs, suggesting that Ssa2p has a chaperone-like activity for
RNAs. Ssa2p also binds Nup116, one of the yeast nucleoporins. Sis1p and Ydj1p,
cytoplasmic co-chaperones for Ssa proteins, were also found to contribute to the
tRNA import. These results unveil a novel function of the Ssa2p system as a tRNA
carrier for nuclear import by a novel mode of substrate recognition. Such Ssa2p
mediated tRNA import likely contributes to quality control of cytosolic tRNAs.
PMID- 25853348
TI - Assessment of an incidental finding of left bundle-branch block.
AB - Incidental left bundle-branch block occurs in up to 1.5% of healthy adults
without symptoms or signs of cardiovascular disease. It may be found during
investigation for non-cardiac disease, during preoperative assessment, private
health screening or inpatient monitoring. This article outlines how to assess
these patients.
PMID- 25853349
TI - Obstructive sleep apnoea associated with syringomyelia.
AB - Coexistence of obstructive sleep apnoea and syringomyelia is quite rare. This
article discusses three cases of coexisting obstructive sleep apnoea and
syringomyelia and looks at the possible mutual influences between the two
diseases.
PMID- 25853351
TI - Breast reconstruction: one size does not fit all.
PMID- 25853350
TI - Splenic injury: diagnosis and management.
AB - Better understanding of the dual functionality of the spleen has led to a
conservative approach to splenic trauma. With accurate assessment and vigilant
clinical examination up to two thirds of splenic injuries can be managed
expectantly; when surgery is unavoidable, splenic preserving techniques may be
used to maintain function.
PMID- 25853352
TI - Implant-based breast reconstruction with meshes and matrices: biological vs
synthetic.
AB - This article presents an overview of the different acellular dermal matrices and
synthetic meshes used in modern-day primary and secondary implant-based breast
reconstruction. Case examples are given, along with a description of the senior
author's pioneering direct-to-implant reconstruction.
PMID- 25853353
TI - PICOTM incision closure in oncoplastic breast surgery: a case series.
AB - Single-use negative pressure wound therapy (PICOTM) has been used on high-risk
surgically incised wounds with encouraging results, but there is no evidence for
its use in oncoplastic breast surgery. This article reports a case series with
closed incisions in oncoplastic breast procedures following the introduction of
PICOTM.
PMID- 25853354
TI - Deprivation of Liberty Safeguards: ethical and clinical implications.
AB - The Deprivation of Liberty Safeguards were introduced in 2009 as an addition to
the Mental Capacity Act 2005. This review discusses the legal impact of the
Deprivation of Liberty Safeguards in the management of incapacitated patients.
PMID- 25853355
TI - Medical students' perceptions of the situational judgement test: a mixed methods
study.
AB - The situational judgement test is a UK-based assessment tool for determining job
allocation for exiting medical students which has been shown to be reliable and
valid. This study assessed medical students' perceptions of the situational
judgement test, having undergone the assessment, and reviewed the findings.
PMID- 25853356
TI - Clinical leadership effectiveness, change and complexity.
AB - This article explores how an understanding of approaches to leading and managing
change and complexity science can help clinical leaders engage with and manage
change in complex environments and systems more effectively.
PMID- 25853357
TI - Successful intravenous thrombolysis following full dose rivaroxaban 5 hours
before ictus.
PMID- 25853358
TI - Metastatic renal carcinoma: a question of management.
PMID- 25853359
TI - Absent inferior vena cava: an unusual cause of recurrent deep vein thrombosis.
PMID- 25853360
TI - Sir John Tomes: father of modern dental surgery in England.
PMID- 25853361
TI - The Five year forward view: issues of funding and the ageing population still
need addressing.
PMID- 25853362
TI - Tramadol-related hypoglycaemia and tramadol-induced anorexia.
PMID- 25853363
TI - Should we be cooling patients after out of hospital cardiac arrest?
PMID- 25853364
TI - The pupillary examination.
PMID- 25853365
TI - A guide to magnetic resonance imaging in clinical practice.
PMID- 25853366
TI - Overview of pancreatic resections: postoperative management.
PMID- 25853368
TI - Photodynamic therapy: a review of applications in neurooncology and
neuropathology.
PMID- 25853367
TI - Dressing up Nanoparticles: A Membrane Wrap to Induce Formation of the Virological
Synapse.
AB - Next-generation nanoparticle-based drug delivery systems require the ability to
target specific organelles or subcellular regions in selected target cells. Human
immunodeficiency virus type I (HIV-1) particles are evolutionarily optimized
nanocarriers that have evolved to avoid intracellular degradation and achieve
enrichment at the synapse between mature dendritic cells (mDCs) and T cells by
subverting cellular trafficking mechanisms. This study demonstrates that
integration of the glycosphingolipid, GM3, in a membrane around a solid
nanoparticle (NP) core is sufficient to recapitulate key aspects of the virus
particle trafficking in mDCs. GM3-presenting artificial virus NPs (GM3-AVNs)
accumulate in CD169(+) and CD81(+) nonlysosomal compartments in an actin
dependent process that mimics the sequestration of HIV-1. Live-cell optical
tracking studies reveal a preferential recruitment and arrest of surface scanning
CD4(+) T cells in direct vicinity to the AVN-enriched compartments. The formed
mDC-T cell conjugates exhibit strong morphological similarities between the GM3
AVN-containing mDC-T cell synapse and the HIV-1 virological synapse, indicating
that GM3-CD169 interactions alone are sufficient for establishing the mDC-T cell
virological synapse. These results emphasize the potential of the GM3-AVN
approach for providing therapeutic access to a key step of the host immune
response--formation of the synaptic junction between an antigen-presenting cell
(mDC) and T cells--for modulating and controlling immune responses.
PMID- 25853369
TI - Short-term Results of a Magnetic Resonance Imaging-Based Swedish Screening
Program for Individuals at Risk for Pancreatic Cancer.
AB - IMPORTANCE: Pancreatic cancer is the fourth leading cause of cancer-related death
in Western countries. In approximately 10% of all patients with pancreatic
cancer, it is possible to define a positive family history for pancreatic cancer
or for one of the other related genetic syndromes. A screening program for
individuals at risk is recommended; however, surveillance modalities have not
been defined yet. OBJECTIVE: To analyze the short-term results of a prospective
clinical surveillance program for individuals at risk for pancreatic cancer using
a noninvasive magnetic resonance imaging (MRI)-based screening protocol. DESIGN,
SETTING AND PARTICIPANTS: A prospective observational study of all patients with
a genetic risk for developing pancreatic cancer who were referred to Karolinska
University Hospital between January 1, 2010, and January 31, 2013, using an MRI
based surveillance program. All patients were investigated for the most common
genetic mutations associated with pancreatic cancer. EXPOSURE: A noninvasive MRI
based screening protocol. MAIN OUTCOMES AND MEASURES: The ability of MRI to
identify potential precancerous or early cancers in individuals at risk for
pancreatic cancer. RESULTS: Forty patients (24 women and 16 men) were enrolled.
The mean age was 49.9 years. The mean length of follow-up was 12.9 months. The
numbers of relatives affected by pancreatic cancer were 5 in 2 patients (5%), 4
in 5 patients (12.5%), 3 in 17 patients (42.5%), 2 in 14 patients (35%), and 1 in
2 patients (5%). In 4 patients (10%), a p16 mutation was found; in 3, a BRCA2
mutation (7.5%); and in 1, a BRCA1 mutation (2.5%). In 16 patients (40%), MRI
revealed a pancreatic lesion: intraductal papillary mucinous neoplasia (14
patients, 35%) and pancreatic ductal adenocarcinoma (2 patients, 5%). One patient
had a synchronous intraductal papillary mucinous neoplasia and pancreatic ductal
adenocarcinoma. Five patients (12.5%) required surgery (3 for pancreatic ductal
adenocarcinoma and 2 for intraductal papillary mucinous neoplasia), while the
remaining 35 are under continued surveillance. CONCLUSIONS AND RELEVANCE: During
a median follow-up of approximately 1 year, pancreatic lesions were detected in
40% of the patients, of whom 5 underwent surgery. Although the study time was
relatively short, the surveillance program in individuals at risk seems to be
effective.
PMID- 25853370
TI - Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma
oxytocin levels.
AB - Many drugs, including alcohol and stimulants, demonstrably increase sociability
and verbal interaction and are recreationally consumed in social settings. One
drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its
prosocial effects by increasing plasma oxytocin levels, and the oxytocin system
has been implicated in responses to several other drugs of abuse. Here, we sought
to investigate the effects of 2 other "social" drugs on plasma oxytocin levels-
methamphetamine and alcohol. Based on their shared capacity to enhance
sociability, we hypothesized that both methamphetamine and alcohol would increase
plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3
sessions during which they received methamphetamine (10 mg or 20 mg) or placebo
under double-blind conditions. Subjective drug effects, cardiovascular effects,
and plasma oxytocin levels were measured at regular intervals throughout the
sessions. In study 2, 8 healthy adult volunteers attended a single session during
which they received 1 beverage containing placebo, and then a beverage containing
alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma
oxytocin levels were measured at regular intervals. Both methamphetamine and
alcohol produced their expected physiological and subjective effects, but neither
of these drugs increased plasma oxytocin levels. The neurobiological mechanisms
mediating the prosocial effects of drugs such as alcohol and methamphetamine
remain to be identified.
PMID- 25853371
TI - The prevalence of lithium-associated hyperparathyroidism in a large Swedish
population attending psychiatric outpatient units.
AB - OBJECTIVE: This retrospective study determined the prevalence of lithium
associated hyperparathyroidism (LHPT) in 2 geographically defined, equivalent
populations in Sweden, with no other selection bias. METHODS: The medical
journals of all patients receiving lithium treatment were examined specifically
regarding their biochemistry: calcium, parathyroid hormone (PTH), creatinine, and
vitamin D. The condition LHPT was defined biochemically. All patient data were
noted, and the prevalence of the condition could thereby be calculated. RESULTS:
A total of 423 patients were included (251 women and 172 men; 3:2), treated over
a mean of 13.5 years (range, 1-46 years), aged 19 to 92. 77 patients (18%) were
identified with LHTP whose median serum calcium was 2.55 mmol/L and PTH was 99
ng/L. A further 21% showed tendencies toward hypercalcemia. Forty-three percent
had vitamin D insufficiency. Five patients (approximately 1%) had undergone
parathyroidectomy. CONCLUSION: The prevalence of LHPT is high and often goes
undetected. Vitamin D insufficiency is common as is polypharmacy. Surgery, for
unclear reasons, has not been performed extensively, possibly because of limited
knowledge of the underlying pathophysiology or surgery's significance. We present
standard recommendations on patient management and suggest continual, specific
follow-up including the monitoring of calcium, PTH, and vitamin D at least
annually. Surgery should be considered with intention to improve psychiatric well
being and provide multiorgan protection.
PMID- 25853372
TI - Rapid Fingerprint Analysis of Plant Extracts for Ellagitannins, Gallic Acid, and
Quinic Acid Derivatives and Quercetin-, Kaempferol- and Myricetin-Based Flavonol
Glycosides by UPLC-QqQ-MS/MS.
AB - This paper describes the development of a rapid method with ultraperformance
liquid chromatography-triple-quadrupole mass spectrometry that can specifically
measure group-specific fingerprints from plant extracts for the following
polyphenol groups: (1) ellagitannins, (2) gallic acid derivatives, (3) quinic
acid derivatives, (4) quercetin-based flavonol glycosides, (5) kaempferol-based
flavonol glycosides, and (6) myricetin-based flavonol glycosides. In addition,
the method records simultaneously diode array and full scan mass spectrometry
data that can be used to later characterize and quantify the main individual
polyphenols if necessary. All of this is achieved within the 10 min period of
analysis, which makes the presented method a significant addition to the
chemistry tools currently available for the rapid analysis of complex polyphenol
mixtures from plant extracts.
PMID- 25853373
TI - Indeed, why wound care?
PMID- 25853374
TI - Nutrition 411: Exercising to improve body composition.
PMID- 25853375
TI - The alliance of wound care stakeholders: advocating for wound care.
PMID- 25853376
TI - A cross-sectional pilot study to examine food sufficiency and assess nutrition
among low-income patients with injection-related venous ulcers.
AB - Adequate nutrition has long been considered a critical component for wound
healing, but literature regarding the relationship between nutrition and venous
ulcer (VU) healing is limited. A person's nutrition is affected by the
availability of food as well as his/her overall health. Food sufficiency and
nutrition are important concerns in the care of persons of low income with
injection-related VUs, which tend to be large and slow to heal. A cross-sectional
pilot study was conducted to explore the relationship between food
sufficiency/security and nutrition with regard to demographic, wound, quality-of
life, physical activity, falls, and fall risk variables. Nutrition was examined
using 2 well-developed instruments that measure food sufficiency/security and
assess nutrition--the United States Department of Agriculture's Adult Food
Sufficiency Questionnaire (FSQ) and the Nestle Mini Nutritional Assessment (MNA).
All participants (N = 31, 54% men, mean age 56.1 +/- 3.6 years, all African
American) were recruited from an outpatient clinic. All had injection-related VUs
from a history of injecting illicit substances. In terms of food
sufficiency/security, most participants (26, 84%) reported having enough food in
the house, but 10 (32%) worried about running out of food. From 16% to 22.6% of
participants expressed concern with food sufficiency/security in terms of cutting
meal size, eating less, hunger, and weight loss. Food sufficiency/security was
high for 19 (61.3%), but 12 (39%) had marginal or lower food
sufficiency/security. MNA scores showed 16 participants (52%) were at risk of
malnutrition or malnourished. Low food sufficiency/security was significantly (P
<0.05) associated with less motivation for activity (r = -0.40) and less walking
(r = -0.36). Better nutrition assessment scores were significantly associated (P
<0.01) with fewer comorbidities (r = -0.57) and falls (r = -0.46) and with higher
quality of life (r = 0.50), motivation for physical activity (r = 0.59), and
balance confidence (r = 0.60). Both food security and nutrition assessment are
important to assess in low-income persons with injection-related VUs. A number of
significant relationships of the FSQ and MNA to other variables was found but
needs further investigation with a larger sample.
PMID- 25853377
TI - Pressure ulcer prevention algorithm content validation: a mixed-methods,
quantitative study.
AB - Translating pressure ulcer prevention (PUP) evidence-based recommendations into
practice remains challenging for a variety of reasons, including the perceived
quality, validity, and usability of the research or the guideline itself.
Following the development and face validation testing of an evidence-based PUP
algorithm, additional stakeholder input and testing were needed. Using
convenience sampling methods, wound care experts attending a national wound care
conference and a regional wound ostomy continence nursing (WOCN) conference
and/or graduates of a WOCN program were invited to participate in an Internal
Review Board-approved, mixed-methods quantitative survey with qualitative
components to examine algorithm content validity. After participants provided
written informed consent, demographic variables were collected and participants
were asked to comment on and rate the relevance and appropriateness of each of
the 26 algorithm decision points/steps using standard content validation study
procedures. All responses were anonymous. Descriptive summary statistics, mean
relevance/appropriateness scores, and the content validity index (CVI) were
calculated. Qualitative comments were transcribed and thematically analyzed. Of
the 553 wound care experts invited, 79 (average age 52.9 years, SD 10.1; range 23
73) consented to participate and completed the study (a response rate of 14%).
Most (67, 85%) were female, registered (49, 62%) or advanced practice (12, 15%)
nurses, and had > 10 years of health care experience (88, 92%). Other health
disciplines included medical doctors, physical therapists, nurse practitioners,
and certified nurse specialists. Almost all had received formal wound care
education (75, 95%). On a Likert-type scale of 1 (not relevant/appropriate) to 4
(very relevant and appropriate), the average score for the entire algorithm/all
decision points (N = 1,912) was 3.72 with an overall CVI of 0.94 (out of 1). The
only decision point/step recommendation with a CVI of <= 0.70 was the
recommendation to provide medical-grade sheepskin for patients at high risk for
friction/shear. Many positive and substantive suggestions for minor modifications
including color, flow, and algorithm orientation were received. The high overall
and individual item rating scores and CVI further support the validity and
appropriateness of the PUP algorithm with the addition of the minor
modifications. The generic recommendations facilitate individualization, and
future research should focus on construct validation testing.
PMID- 25853378
TI - Predictive validity and reliability of the Turkish version of the risk assessment
pressure sore scale in intensive care patients: results of a prospective study.
AB - Multiple pressure ulcer (PU) risk assessment instruments have been developed and
tested, but there is no general consensus on which instrument to use for specific
patient populations and care settings. The purpose of this study was to determine
the reliability and predictive validity of the Turkish version of the Risk
Assessment Pressure Sore (RAPS) instrument, which includes 12 variables--5 from
the modified Norton Scale, 3 from the Braden Scale, and 3 from other research
results--for use in intensive care unit (ICU) patients. The English version of
the RAPS instrument was translated into Turkish and tested for internal
consistency and predictive validity (sensitivity, specificity, positive
predictive value, and negative predictive value) using a convenience sample of
122 patients consecutively admitted to an ICU unit in Turkey. The patients were
assessed within 24 hours of admission, and after that, once a week until the
development of a PU or discharge from the unit. The incidence of PUs in this
population was 23%. The majority of ulcers that developed were Stage I. Internal
consistency of the RAPS tool was adequate (Cronbach's alpha = 0.81). The best
balance between sensitivity and specificity for ICU patients was reached at a cut
off point of <= 27 (ie, sensitivity = 74.2%, specificity = 31.8%, positive
predictive value = 38.7%, and negative predictive value 91.3%). This is lower
than the cut-off point reported in other studies of the RAPS scale. In this
population of ICU patients, the RAPS scale was found to have acceptable
reliability and poor validity. Additional studies to evaluate the predictive
validity and reliability of the RAPS scale in other patient populations and care
settings are needed.
PMID- 25853379
TI - Using active Leptospermum honey in the debridement process: 6 challenging cases
from the inner city.
AB - The use of honey-based dressings has been documented for thousands of years.
Recent studies suggest their effectiveness may be, in part, related to their
ability to facilitate autolytic debridement. Six patients who presented with
multiple comorbidities and risk factors for delayed healing whose wounds required
debridement were managed with active Leptospermum honey (ALH) to evaluate the
safety and effectiveness of this treatment modality. The 6 patients ranged in age
from 39 to 81 years. The ALH was covered with a foam dressing; both dressings
were changed approximately every 3 days. After 9 to 20 days of use, wounds were
completely, or almost completely, debrided, and a 75% concomitant average
increase in the amount of granulation tissue in the wound bed was observed. No
adverse events were noted. The use of ALH in this case series was effective, and
no surgical debridement was needed. Research to compare the efficacy of ALH to
other debridement methods is warranted.
PMID- 25853381
TI - Incidence and survival of gynecologic sarcomas in England.
AB - OBJECTIVE: Gynecologic sarcomas account for approximately 3% to 4% of all
gynecologic malignancies and are associated with poor outcomes compared with
gynecologic carcinomas. The aim of this study is to report the incidence and
survival rates of the main gynecologic sarcomas using national English cancer
registration data. METHODS/MATERIALS: Records of gynecologic sarcomas diagnosed
between 1985 and 2008 were extracted from the English National Cancer Data
Repository. ICD-O3 morphology codes were used to assign tumor records to specific
histologic subgroups. Incidence and 5-year relative survival rates were
calculated. RESULTS: There were 5316 new cases of gynecologic sarcoma diagnosed
in England between 1985 and 2008. Incidence rates increased significantly in the
early 1990s, probably due to coding changes. Age-specific incidence rates were
highest in women aged between 45 and 64 years. In the most recent period studied
(2001-2008), incidence rates fluctuated between 8 and 9.6 per million. The most
common anatomical site was the uterus (83% of all diagnoses), and the most common
histologic diagnosis was leiomyosarcoma (52% of all diagnoses). Overall 5-year
relative survival increased significantly between 1985-1989 and 2000-2004, from
34% to 48%. CONCLUSIONS: Gynecologic sarcoma incidence rates have varied little
since 1993, whereas survival has improved significantly. These results are
consistent with previously published small series and case studies, and provide a
more complete picture of gynecologic sarcoma incidence and survival patterns in
England.
PMID- 25853380
TI - HIV Status and Acute Hematologic Toxicity Among Patients With Cervix Cancer
Undergoing Radical Chemoradiation.
AB - INTRODUCTION: Women infected with the human immunodeficiency virus (HIV) have a
higher risk of developing cervix carcinoma than do other women who are thought to
be more vulnerable to acute toxicities during chemoradiation. We compared HIV
positive/HIV-negative patients with cervix carcinoma at a single institution with
respect to cancer treatment toxicities. METHODS AND MATERIALS: Among patients
with stage Ib1-IIIb invasive cervical carcinoma who received radiation or
chemoradiation with curative intent, we evaluated demographic and clinical
characteristics of HIV-positive and HIV-negative patients. Treatment regimens
were documented and toxicities scored as per Radiation Therapy Oncology Group
guidelines. We developed logistic regression models for the associations of grade
3/4 toxicities with HIV status. RESULTS: Complete data were available on 213
patients, including 36 (16.8%) who were HIV positive. More than 85% of both HIV
positive and HIV-negative patients received a minimum of 68-Gy equivalent dose in
2-Gy-fraction external beam and high-dose-rate brachytherapy. More HIV-positive
than HIV-negative patients were prescribed radiation alone (38.9% vs 24.29%, P =
0.01), experienced at least 1 grade 3/4 toxicity (38.9% vs 26.6%), or developed
grade 3/4 leucopenia (30.6% vs 10.2%, P = 0.003).In a multivariable model,
patients who developed a grade 3/4 toxicity were 4 times as likely to have
received chemotherapy (odds ratio, 4.41 [95% confidence interval, 1.76-11.1]; P =
0.023) and twice as likely to be HIV positive (odds ratio 2.16 [95% confidence
interval, 0.98-4.8]; P = 0.05) as women who did not experience such toxicities.
CONCLUSIONS: HIV-positive patients with cervical carcinoma received adequate
radiotherapy but were less likely than HIV-negative patients to complete
chemotherapy. Few HIV-positive or HIV-negative patients who received radiotherapy
without chemotherapy experienced grade 3/4 toxicity. However, among patients who
received chemotherapy, those who were HIV positive were more likely than others
to experience hematologic toxicity.
PMID- 25853382
TI - Does Lymphadenectomy Improve Survival in Uterine Leiomyosarcoma?
AB - INTRODUCTION: The role of lymphadenectomy in the management of uterine
leiomyosarcoma (LMS) is controversial. We aimed to identify whether lymph node
dissection (LND) has any survival benefit in uterine LMS. METHODS: Data of 95
patients with histologically proven uterine LMS from 2 tertiary centers (1993
through 2009) were retrospectively analyzed. Kaplan-Meier and Cox proportional
hazards regression models were used for analyses. RESULTS: Mean age was 51.5
years. Thirty-six (37.9%) underwent LND. The median lymph node count was 54.
Eight (22.2%) patients had lymphatic metastasis. Median follow-up was 26 months.
Sixty-two (65%) patients had recurrence and 48 (50.5%) died. Median disease-free
survival (DFS) was 19 months for both group of patients who had or did not have
LND, and median overall survival (OS) was 29 and 26 months, respectively (P =
0.4). Five-year DFS was 35.9% vs 26.8% (P = 0.4), and 5-year OS was 45.4% vs
43.8% (P = 0.22) for the groups. Multivariate analyses did not reveal a single
independent prognostic factor in respect to DFS or OS. CONCLUSION: Higher rate of
lymph node metastasis in patients with extrauterine disease indicated the
importance of LND in LMS. However, the survival benefit of lymphadenectomy could
not be shown.
PMID- 25853383
TI - Pelvic Exenteration in Gynecologic Cancer: La Paz University Hospital Experience.
AB - BACKGROUND: Pelvic exenteration is an ultraradical surgery involving the en bloc
resection of the pelvic organs, including the internal reproductive organs, the
distal urinary tract (ureters, bladder, urethra), and/or anorectum. It is mainly
applied as a salvage surgery for recurrent gynecologic tumors of any origin
(vulva, vagina, cervix, uterine, and also ovary). Our aim was to establish the
most favorable cases for this type of surgery by means of a review of our
institution experience. METHODS: Retrospective analyses of all patients treated
with pelvic exenteration for recurrent gynecologic cancer from 2008 to 2014 at La
Paz University Hospital. RESULTS: Ten patients underwent pelvic exenteration for
recurrent gynecologic cancers including uterine, cervical, vaginal, vulvar, and
ovarian cancer. All patients had received prior treatment: surgery, radiotherapy,
and/or chemotherapy. Eight patients underwent total pelvic exenteration, one
anterior and one posterior pelvic exenteration. Urinary diversions technique
consisted of ileal conduits in all cases. Permanent colostomy was performed in
all cases. Postoperative complications were related to the urinary diversion in
50% of the cases, to the reconstructive technique in 30%, and to systemic or
pelvic infections in 20%. CONCLUSIONS: Despite the high morbidity and mortality
rates, pelvic exenteration is feasible, and in selected cases of cancer
recurrence is the last possible treatment.
PMID- 25853384
TI - Sentinel Lymph Node Biopsy in Endometrial Cancer--Comparison of 2 Detection
Methods.
AB - OBJECTIVES: Sentinel lymph node biopsy (SLNB) can identify patients with nodal
metastases who are eligible for tailored treatment. The aim of study was to
compare the SLN detection rates using cervical and subserosal administration of 2
tracers. RESULTS: In group 1 (82 patients), SLNB was performed using radiocolloid
injected to the cervix and blue dye administered to the fundus. In group 2, blue
dye was injected to cervix and fundus (106 patients). Only SLNB was performed in
128 (68.1%) women. In the remaining 60 (31.9%) patients, pelvic/para-aortic
lymphadenectomy together with SLNB was performed. Groups 1 and 2 did not differ
with regard to the frequencies of SLNB and lymphadenectomy. The detection rate
for both groups was 90.9%. Bilateral detection was achieved in 72.5%. Para-aortic
SLNs were found in 9.6%. Detection rates in groups 1 and 2 were 95.1% and 87.7%
(P = 0.065). In comparison of cervical administration of radioisotope and
subserosal injection of blue dye in group 1, we found a significant difference
for total SLN detection (91.5% vs 74.4%, P < 0.05) and no significant difference
for bilateral detection (73.3% vs 59.1%, P = 0.776). We did not find differences
in the para-aortic SLN detection rates achieved after administration of a
radiotracer and injection of a blue dye (4.9% vs 9.8%, P = 0.184). Eighteen
patients (9.6%) presented with nodal disease, including 15 women with SLN
involvement. The false-negative rate, calculated for patients subjected to
lymphadenectomy, was 12.5% (1/8); using the SLNB surgical algorithm, it was 10%
(1/10). CONCLUSIONS: Cervical administration of a tracer, especially
radioisotope, results in high SLN detection rates. In turn, the subserosal
injection can be used only as an adjuvant method for SLNB. Low para-aortic SLN
detection rates observed after cervical administration of a tracer do not seem to
be a serious limitation of this technique.
PMID- 25853385
TI - Pretreatment Mean Apparent Diffusion Coefficient Is Significantly Correlated With
Event-Free Survival in Patients With International Federation of Gynecology and
Obstetrics Stage Ib to IIIb Cervical Cancer.
AB - OBJECTIVES: To assess the prognostic impact of the pretreatment mean apparent
diffusion coefficient (ADCmean) values of tumors obtained by diffusion-weighted
magnetic resonance imaging. We evaluated the prognostic value of the ADCmean for
event-free survival (EFS) and overall survival (OS) among patients with uterine
cervical cancer. METHODS/MATERIALS: We included 171 patients diagnosed as having
International Federation of Gynecology and Obstetrics stage Ib to IIIb cervical
cancer by pretreatment magnetic resonance imaging scans, regardless of
therapeutic methods. In all patients and in patients with squamous cell carcinoma
(SCC; n = 123), the optimal cutoff values of the tumor ADCmean for EFS and for OS
were determined, respectively. The prognostic significance of the ADCmean was
evaluated using univariate and multivariate Cox regression analyses. RESULTS: In
the univariate analyses, the ADCmean values were significantly associated with
negative effects on EFS both in all patients and in patients with SCC, while not
being significantly associated with OS in both groups. In the multivariate
analysis, ADCmean was an independent biomarker for EFS (P < 0.05) in patients
with SCC along with lymph node metastasis and definitive surgery, whereas ADCmean
was not independently significant in EFS in all patients. CONCLUSIONS: The
pretreatment ADCmean value of the tumor was an independent prognostic factor for
EFS in International Federation of Gynecology and Obstetrics stage Ib to III SCC
of the uterine cervix.
PMID- 25853386
TI - VO2max Measured with a Self-selected Work Rate Protocol on an Automated
Treadmill.
AB - PURPOSE: The use of graded maximal exercise tests for measuring maximal oxygen
consumption (VO2max) is common practice in both cardiopulmonary rehabilitation
settings and in sports medicine research. Recent alterations of common testing
protocols to allow for self-selected work rates (SPV) have elicited VO2max values
similar to or higher than more traditional style protocols (TP). Research is
lacking in the delivery of the SPV protocol using a treadmill modality. The
purpose of the study was to examine the validity of an SPV using an automated
treadmill for measuring cardiorespiratory fitness. METHODS: Thirteen experienced
endurance runners completed three maximal exercise tests on a treadmill. Oxygen
consumption was measured using a computerized system and averaged more than 30-s
time periods. SPV was completed using an automated treadmill that consisted of a
sonar range finder, microcontroller, and customized computer software. Subject
deviations from the middle of the treadmill belt resulted in rapid, graded
increases or decreases in speed. TP was completed on the same treadmill without
the use of the automated software. A verification phase protocol (VP) was used to
verify if VO2 was maximal. RESULTS: Peak work rate achieved during SPV was
significantly greater than that achieved during TP by 1.2 METs; P < 0.05, d =
0.564. Oxygen consumption was significantly greater in TP (64.9 +/- 8.2
mL.kg.min) than SPV (63.4 +/- 7.8 mL.kg.min); P < 0.005, d = 0.195. CONCLUSION:
An automated treadmill allowed for the completion of SPV similar to what has been
reported for cycling. SPV with an automated treadmill did not provide a higher
VO2max than TP despite higher work rates.
PMID- 25853387
TI - Factors that affect willingness to donate blood for the purpose of biospecimen
research in the Korean American community.
AB - OBJECTIVE: Biorepositories have been key resources in examining genetically
linked diseases, particularly cancer. Asian Americans contribute to
biorepositories at lower rates than other racial groups, but the reasons for this
are unclear. We hypothesized that attitudes toward biospecimen research mediate
the relationship between demographic and healthcare access factors, and
willingness to donate blood for research purposes among individuals of Korean
heritage. METHODS: Descriptive statistics and bivariate analyses were utilized to
characterize the sample with respect to demographic, psychosocial, and behavioral
variables. Structural equation modeling with 5000 re-sample bootstrapping was
used to assess each component of the proposed simple mediation models. RESULTS:
Attitudes towards biospecimen research fully mediate associations between age,
income, number of years lived in the United States, and having a regular
physician and willingness to donate blood for the purpose of research.
CONCLUSION: Participants were willing to donate blood for the purpose of research
despite having neutral feelings towards biospecimen research as a whole.
Participants reported higher willingness to donate blood for research purposes
when they were older, had lived in the United States longer, had higher income,
and had a regular doctor that they visited. Many of the significant relationships
between demographic and health care access factors, attitudes towards biospecimen
research, and willingness to donate blood for the purpose of research may be
explained by the extent of acculturation of the participants in the United
States.
PMID- 25853388
TI - Treatment of severe ocular surface disorders with albumin eye drops.
AB - PURPOSE: Promising healing effects by albumin eye drops (AED) on the corneal
epithelium have been demonstrated. The aim of this study was to analyze
retrospectively if AED are an effective treatment for severe ocular surface
defects and if recurrences can be reduced. METHODS: Seventeen patients with
persistent epithelial defects (PED) and 30 patients with sterile corneal ulcers
(CU) were treated either with 5% AED or 0.1% hyaluronan eye drops (HED) 8 times
daily until complete epithelium closure. Sizes of the corneal defects, length of
treatment and follow-up period, as well as recurrence rate were evaluated. Follow
up of PED was carried out for 126 +/- 21 days in the AED group and 142 +/- 39
days in the HED group. For CU cases, regular follow-up visits were performed for
117 +/- 15 days in the AED group and 112 +/- 28 days in the HED group. RESULTS:
Nine patients in PED group were treated for 11 +/- 4 days with AED and the HED
group (8 patients) was treated for 10 +/- 3 days until corneal epithelium was
closed, with only one recurrence in the HED group (P = 0.67). Fifteen patients in
CU group were treated for 18 +/- 6 days with AED and the HED group (15 patients)
was treated for 21 +/- 7 days until epithelial closure, with 1 recurrence in the
AED group and 8 in the HED group (P = 0.03). CONCLUSION: This comparative
retrospective case-control study showed that AED are able to close corneal
epithelial defects like CU and PED as good as HED. Even though times of healing
were similar for both treatments, AED seem to reduce the recurrence of sterile
CU. Our findings suggest that AED might be beneficial in the management of ocular
surface epithelial damage; however, further larger studies are necessary to
confirm these results.
PMID- 25853390
TI - Synthetic cannabinoids pharmacokinetics and detection methods in biological
matrices.
AB - Synthetic cannabinoids (SC), originally developed as research tools, are now
highly abused novel psychoactive substances. We present a comprehensive
systematic review covering in vivo and in vitro animal and human pharmacokinetics
and analytical methods for identifying SC and their metabolites in biological
matrices. Of two main phases of SC research, the first investigated therapeutic
applications, and the second abuse-related issues. Administration studies showed
high lipophilicity and distribution into brain and fat tissue. Metabolite
profiling studies, mostly with human liver microsomes and human hepatocytes,
structurally elucidated metabolites and identified suitable SC markers. In
general, SC underwent hydroxylation at various molecular sites, defluorination of
fluorinated analogs and phase II metabolites were almost exclusively
glucuronides. Analytical methods are critical for documenting intake, with
different strategies applied to adequately address the continuous emergence of
new compounds. Immunoassays have different cross-reactivities for different SC
classes, but cannot keep pace with changing analyte targets. Gas chromatography
and liquid chromatography mass spectrometry assays - first for a few, then
numerous analytes - are available but constrained by reference standard
availability, and must be continuously updated and revalidated. In blood and oral
fluid, parent compounds are frequently present, albeit in low concentrations; for
urinary detection, metabolites must be identified and interpretation is complex
due to shared metabolic pathways. A new approach is non-targeted HRMS screening
that is more flexible and permits retrospective data analysis. We suggest that
streamlined assessment of new SC's pharmacokinetics and advanced HRMS screening
provide a promising strategy to maintain relevant assays.
PMID- 25853389
TI - Targeting class I histone deacetylase 2 in MYC amplified group 3 medulloblastoma.
AB - INTRODUCTION: Medulloblastoma (MB) is the most frequent malignant brain tumor in
children. Four subgroups with distinct genetic, epigenetic and clinical
characteristics have been identified. Survival remains particularly poor in
patients with Group 3 tumors harbouring a MYC amplification. We herein explore
the molecular mechanisms and translational implications of class I histone
deacetylase (HDAC) inhibition in MYC driven MBs. MATERIAL AND METHODS: Expression
of HDACs in primary MB subgroups was compared to normal brain tissue. A panel of
MB cell lines, including Group 3 MYC amplified cell lines, were used as model
systems. Cells were treated with HDAC inhibitors (HDACi) selectively targeting
class I or IIa HDACs. Depletion of HDAC2 was performed. Intracellular HDAC
activity, cellular viability, metabolic activity, caspase activity, cell cycle
progression, RNA and protein expression were analyzed. RESULTS: HDAC2 was found
to be overexpressed in MB subgroups with poor prognosis (SHH, Group 3 and Group
4) compared to normal brain and the WNT subgroup. Inhibition of the enzymatic
activity of the class I HDACs reduced metabolic activity, cell number, and
viability in contrast to inhibition of class IIa HDACs. Increased sensitivity to
HDACi was specifically observed in MYC amplified cells. Depletion of HDAC2
increased H4 acetylation and induced cell death. Simulation of clinical
pharmacokinetics showed time-dependent on target activity that correlated with
binding kinetics of HDACi compounds. CONCLUSIONS: We conclude that HDAC2 is a
valid drug target in patients with MYC amplified MB. HDACi should cover HDAC2 in
their inhibitory profile and timing and dosing regimen in clinical trials should
take binding kinetics of compounds into consideration.
PMID- 25853391
TI - Phase separation kinetics in amorphous solid dispersions upon exposure to water.
AB - The purpose of this study was to develop a novel fluorescence technique employing
environment-sensitive fluorescent probes to study phase separation kinetics in
hydrated matrices of amorphous solid dispersions (ASDs) following storage at high
humidity and during dissolution. The initial miscibility of the ASDs was
confirmed using infrared (IR) spectroscopy and differential scanning calorimetry
(DSC). Fluorescence spectroscopy, as an independent primary technique, was used
together with conventional confirmatory techniques including DSC, X-ray
diffraction (XRD), fluorescence microscopy, and IR spectroscopy to study phase
separation phenomena. By monitoring the emission characteristics of the
environment-sensitive fluorescent probes, it was possible to successfully monitor
amorphous-amorphous phase separation (AAPS) as a function of time in probucol
poly(vinylpyrrolidone) (PVP) and ritonavir-PVP ASDs after exposure to water. In
contrast, a ritonavir-hydroxypropylmethylcellulose acetate succinate (HPMCAS)
ASD, did not show AAPS and was used as a control to demonstrate the capability of
the newly developed fluorescence method to differentiate systems that showed no
phase separation following exposure to water versus those that did. The results
from the fluorescence studies were in good agreement with results obtained using
various other complementary techniques. Thus, fluorescence spectroscopy can be
utilized as a fast and efficient tool to detect and monitor the kinetics of phase
transformations in amorphous solid dispersions during hydration and will help
provide mechanistic insight into the stability and dissolution behavior of
amorphous solid dispersions.
PMID- 25853392
TI - A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip
improves data quality and performance in epigenome-wide association studies.
AB - DNA methylation plays a fundamental role in the regulation of the genome, but the
optimal strategy for analysis of genome-wide DNA methylation data remains to be
determined. We developed a comprehensive analysis pipeline for epigenome-wide
association studies (EWAS) using the Illumina Infinium HumanMethylation450
BeadChip, based on 2,687 individuals, with 36 samples measured in duplicate. We
propose new approaches to quality control, data normalisation and batch
correction through control-probe adjustment and establish a null hypothesis for
EWAS using permutation testing. Our analysis pipeline outperforms existing
approaches, enabling accurate identification of methylation quantitative trait
loci for hypothesis driven follow-up experiments.
PMID- 25853393
TI - Outcome of complete intrastromal ring implantation using femtosecond laser in
pellucid marginal degeneration.
AB - PURPOSE: To evaluate the effect of complete intrastromal corneal ring
implantations on patients with pellucid marginal degeneration (PMD). DESIGN:
Prospective interventional case series. PATIENTS AND METHODS: Thirty-three eyes
with PMD were included into the study. After pocket creation with femtosecond
laser (Femtec; 20/10 PerfectVision), MyoRing implantation was performed.
Uncorrected and corrected distance visual acuity (UDVA, CDVA), subjective
refraction, keratometry, central corneal thickness, corneal biomechanical profile
(Ocular Response Analysis), and whole-eye wavefront aberrometry (iTrace) were
evaluated preoperatively and also postoperatively, 1 month, 3 months, 6 months,
and 1 year after the operation. RESULTS: One month after surgery, significant
improvements were observed in UDVA (ANOVA; P=0.02), mean keratometry, sphere
(ANOVA; P <0.001), and cylinder (ANOVA; P=0.04) with no significant changes
afterwards. No significant change occurred in the corneal biomechanical profile.
Primary coma and trefoil reduced after 1 year (ANOVA; P values were 0.02 and
0.06, respectively). Primary spherical aberration significantly increased
according to the 1-year follow-up (ANOVA; P<0.001). No significant complication
was observed. CONCLUSION: MyoRing is considered as a treatment modality for
spherocylindrical correction in patients with PMD, with an acceptable safety and
efficacy profile.
PMID- 25853394
TI - Ethnic variation in rhegmatogenous retinal detachments.
AB - PURPOSE: We aimed to investigate the clinical variation of rhegmatogenous retinal
detachments (RD) in patients of different ethnicities. METHODS: Patients
presenting with a primary RD from two ethnic groups were recruited from our
tertiary referral hospital between August 2010 and December 2012. Patients who
self-reported their ethnic origin either as European Caucasian (EC) or South
Asian (SA) were included. Exclusion criteria included trauma, previous
vitreoretinal procedures, age under 18 years, complicated cataract surgery and
the presence of syndromes known to be associated with a high prevalence of RD.
Detailed phenotypic data were collected. Descriptive and comparative statistical
analyses were undertaken. RESULTS: 1269 Patients were recruited. 1173 (92.4%)
were EC. Mean age of onset was 58.3 years (EC) and 54.5 years (SA) (P=0.006).
75.3% EC and 58.4% SA were phakic (P<0.001). 12.8% of EC and 19.4% of SA patients
had a lattice retinal degeneration in the affected eye (P=0.003). Refractive
myopia was greater in SA patients (mean: -6.1DS) than EC (-4.2DS) (P=0.032).
Additionally, SA patients had a greater mean axial length (25.65 mm) than EC
(25.06 mm) (P=0.014). No differences were demonstrated in laterality, family
history, type of retinal break or macular status. CONCLUSIONS: SA patients
present with RD at an earlier age and have a more severe phenotype than ECs.
Future management strategies for RD may need to reflect these differences.
PMID- 25853395
TI - Results of conservative management for consecutive esotropia after intermittent
exotropia surgery.
AB - PURPOSE: To examine the clinical course of consecutive esotropia (ET) using
conservative management, after intermittent exotropia (IXT) surgery. METHODS:
This study included 149 out of 151 consecutive patients with ET after IXT
surgery, who were managed conservatively. The clinical course of consecutive ET
was examined and the patients were classified into two groups based on the
duration of esodeviation: (1) >3 weeks (persistent ET group, n=56) and (2) <3
weeks (transient ET group, n=93). Patient characteristics and treatment outcomes,
including the recurrence of exotropia and stereopsis, were compared between the
two groups. RESULTS: All patients with ET were managed with full-time alternate
occlusion and/or with a Fresnel prism. In 149 patients out of 151 consecutive
patients, 82% of ET disappeared at 12-month follow-up and all at the last follow
up visit (31.4+/-23.5 months). At the final visit, a recurrence of exotropia of
>10 prism dioptres was significantly less frequent in the persistent ET group
than in the transient ET group (25% vs 62%, respectively; P=0.01). However,
stereopsis outcome was not significantly different between the two groups, and
stereopsis change was not affected by age. CONCLUSIONS: By using conservative
management only, persistent consecutive ET after IXT surgery disappeared in most
cases by the 1-year follow-up visit after surgery. Recurrence of exotropia was
significantly less frequent in patients with persistent ET, yet the sensory
outcome was not affected by the duration of consecutive ET or age.
PMID- 25853396
TI - Evaluation of choroidal thickness using enhanced depth imaging by spectral-domain
optical coherence tomography in patients with pseudoexfoliation syndrome.
AB - PURPOSE: To investigate the choroidal thickness using optical coherence
tomography in the eyes of patients with unilateral and bilateral
pseudoexfoliation syndrome and to compare them with healthy controls. METHODS: We
studied four groups: (1) affected eyes from 30 patients with unilateral PEX
syndrome affecting the right eye of 17 patients and the left eye of 13 patients;
(2) clinically unaffected eyes of 30 patients with unilateral PEX syndrome; (3)
the eyes of 30 patients with bilateral PEX syndrome; and (4) the eyes of 30
normal healthy subjects. Choroidal thickness was evaluated using high-speed, high
resolution enhanced depth imaging by spectral-domain optical coherence
tomography. Optical coherence tomography features were compared in all groups
using the statistical package SPSS v 15.0. RESULTS: The mean subfoveal choroidal
thicknesses were 237.35+/-58.01 MUm in group 1; 330.75+/-47.84 MUm in group 2;
206.3+/-86.75 MUm in group 3; and 311.8+/-51.42 MUm in group 4. Significant
differences in the mean subfoveal choroidal thickness were found between groups 1
and 2 (P<0.001), groups 1 and 4 (P=0.004), groups 2 and 3 (P<0.001), and groups 3
and 4 (P<0.001). CONCLUSION: In this study, it was observed that clinically
affected eyes of patients with PEX syndrome have significantly thinner choroids
compared with the clinically unaffected eyes of patients with unilateral PEX
syndrome and eyes of healthy controls.
PMID- 25853397
TI - Vitiligo iridis and glaucoma: a rare sequelae of small pox.
AB - PURPOSE: Vitiligo iridis refers to focal areas of iris atrophy as sequelae of
small pox infection. We report a series of patients with unilateral vitiligo
iridis, some of whom presented with secondary open-angle glaucoma. METHODS: Three
patients with vitiligo iridis underwent a comprehensive ophthalmic examination
including intraocular pressure (IOP) measurement, slit lamp biomicroscopy,
gonioscopy, and fundus evaluation. Patients' facial features were also documented
and photographed. RESULTS: All patients were in their sixth decade. Two out the
three had elevated IOP (52 mm Hg and 36 mm Hg) in the same eye as vitiligo
iridis, at initial presentation. Gonioscopy showed patchy iris hyperpigmentation
and fundus evaluation showed glaucomatous optic disc changes in the involved eye.
One patient responded favourably to topical antiglaucoma medications, whereas the
other was taken up for combined phacoemulsification-trabeculectomy with good
results. The third patient had normal IOP in the involved eye. All three patients
gave a history of small pox in childhood and had pitted facial scars typical of
previous small pox infection. CONCLUSIONS: Vitiligo iridis may be associated with
the secondary glaucoma as a long-term sequelae of small pox. It may be prudent to
periodically follow-up such patients for development of raised IOP in the future.
PMID- 25853398
TI - Where is the junction of zone 2 and zone 3 temporal retina in RetCam images of
acute retinopathy of prematurity?
PMID- 25853399
TI - Storage stability of bevacizumab in polycarbonate and polypropylene syringes.
AB - PURPOSE: To compare and examine the storage stability of compounded bevacizumab
in polycarbonate (PC) and polypropylene (PP) syringes over a 6-month period. PC
syringes have been used in a recent clinical study and bevacizumab stability has
not been reported for this type of syringe. METHODS: Repackaged bevacizumab was
obtained from Moorfields Pharmaceuticals in PC and PP syringes. Bevacizumab from
the stored syringes was analysed at monthly time points for a 6-month period and
compared with bevacizumab from a freshly opened vial at each time point. SDS-PAGE
electrophoresis and size-exclusion chromatography (SEC) was used to observe
aggregation and degradation. Dynamic light scattering (DLS) provided information
about the hydrodynamic size and particle size distribution of bevacizumab in
solution. VEGF binding and the active concentration of bevacizumab was determined
by surface plasmon resonance (SPR) using Biacore. RESULTS: SDS-PAGE and SEC
analysis did not show any changes in the presence of higher molecular weight
species (HMWS) or degradation products in PC and PP syringes from T0 to T6
compared with bevacizumab sampled from a freshly opened vial. The hydrodynamic
diameter of bevacizumab in the PC syringe after 6 months of storage was not
significantly different to bevacizumab taken from a freshly opened vial. Using
SPR, the VEGF binding activity of bevacizumab in the PC syringe was comparable to
bevacizumab taken from a freshly opened vial. CONCLUSION: No significant
difference over a 6-month period was observed in the quality of bevacizumab
repackaged into prefilled polycarbonate and polypropylene syringes when compared
with bevacizumab that is supplied from the vial.
PMID- 25853400
TI - Evaluation of the retinal nerve fibre layer and ganglion cell complex thickness
in pituitary macroadenomas without optic chiasmal compression.
AB - PURPOSE: The aim of this prospective study was to measure the thickness of the
circumpapillary retinal nerve fibre layer (cpRNFL) and the ganglion cell complex
(GCC) using spectral domain optical coherence tomography (SD-OCT) in a cohort of
consecutive de novo patients with pituitary macroadenomas without chiasmal
compression. PATIENTS AND METHODS: Twenty-two consecutive patients with pituitary
macroadenoma without chiasmal compression (16 men, 6 women, aged 45.2+/-14.6
years, 43 eyes) entered the study between September 2011 and June 2013. Among
them, 31.8% harboured a growth hormone-secreting pituitary adenoma, 27.3% a
prolactin-secreting pituitary adenoma, 27.3% a corticotrophin-secreting pituitary
adenoma, and 13.6% a non-secreting pituitary tumour. Eighteen subjects (nine
females, nine males, mean age 36.47+/-6.37 years; 33 eyes) without pituitary
adenoma, with normal ophthalmic examination, served as controls. In both patients
and controls, cpRNFL and GCC thicknesses were measured by SD-OCT. RESULTS:
Patients were significantly older (P=0.02) than controls. Best corrected visual
acuity, intraocular pressure, colour fundus photography, and automatic perimetry
test were within the normal range in patients and controls. Conversely, cpRNFL
(P=0.009) and GCC (P<0.0001) were significantly thinner in patients than in
controls. The average GCC (r=0.306, P=0.046) significantly correlated with the
presence of arterial hypertension. OCT parameters did not differ significantly
between patients with a tumour volume above the median and those with a tumour
volume below the median. CONCLUSION: Pituitary macroadenomas, even in the absence
of chiasmal compression, may induce GCC and retinal nerve fibre layer thinning.
SD-OCT may have a role in the early diagnosis and management of patients with
pituitary tumours.
PMID- 25853401
TI - The role of computerised tomography in predicting visual outcome in ocular trauma
patients.
AB - PURPOSE: Ocular blast injuries in the military setting are particularly
associated with significant maxillofacial trauma and/or brain injury. The
opportunity to perform a comprehensive ophthalmic evaluation is frequently
limited in the acute multiple trauma scenario. We aim to describe the
relationship between the clinical effects of acute ocular and orbital blast
trauma with the findings on computerised tomography (CT). METHODS: This was a
retrospective consecutive case series of all soldiers with facial and/or
suspected ocular injuries. A total of 80 eyes that had suffered blast injuries of
varying severity were studied. Assessment of orbital and ocular CT images were
performed by military consultant radiologists. A comparison was made with actual
clinical findings. Statistical analysis was performed using Fisher's exact test.
RESULTS: No pathological findings were described in 37 of the 80 eyes imaged by
orbital and ocular CT scans. Clinically, these eyes and orbits were all found to
be intact, or had minor trauma. All foreign bodies and penetrating eye injuries
were successfully diagnosed by CT. Absence of an orbital fracture did not rule
out a globe injury. However, a corneal or scleral defect was less likely when an
orbital fracture was absent. CONCLUSION: The eye is a delicate structure prone to
injury that requires urgent repair if breached. It is difficult to assess
thoroughly in the unconscious or distressed patient. In this context, CT imaging
is invaluable to be able to make a relatively confident prediction of clinical
findings and decide upon the necessity for acute ophthalmic surgical
intervention.
PMID- 25853403
TI - Recrossing and Tunneling in the Kinetics Study of the OH + CH4 -> H2O + CH3
Reaction.
AB - Thermal rate constants and several kinetic isotope effects were evaluated for the
OH + CH4 hydrogen abstraction reaction using two kinetics approaches, ring
polymer molecular dynamics (RPMD) and variational transition state theory with
multidimensional tunneling (VTST/MT), based on a refined full-dimensional
analytical potential energy surface, PES-2014, in the temperature range 200-2000
K. For the OH + CH4 reaction, at low temperatures, T = 200 K, where the quantum
tunneling effect is more important, RPMD overestimates the experimental rate
constants due to problems associated with PES-2014 in the deep tunneling regime
and to the known overestimation of this method in asymmetric reactions, while
VTST/MT presents a better agreement, differences about 10%, due to compensation
of several factors, inaccuracy of PES-2014, and ignoring anharmonicity. In the
opposite extreme, T = 1000 K, recrossing effects play the main role, and the
difference between both methods is now smaller, by a factor of 1.5. Given that
RPMD results are exact in the high-temperature limit, the discrepancy is due to
the approaches used in the VTST/MT method, such as ignoring the anharmonicity of
the lowest vibrational frequencies along the reaction path, which leads to an
incorrect location of the dividing surface between reactants and products. The
analysis of several kinetic isotope effects, OH + CD4, OD + CH4, and OH +
(12)CH4/(13)CH4, sheds light on these problems and confirms the previous
conclusions. In general, the agreement with the available experimental data is
reasonable, although discrepancies persist, and they have been analyzed as a
function of the many factors affecting the theoretical calculations: limitations
of the kinetics methods and of the potential energy surface, and uncertainties in
the experimental measurements. Finally, in the absence of full-dimensional
quantum mechanics calculations, this study represents an additional step in
understanding this seven-atom hydrogen abstraction reaction.
PMID- 25853402
TI - Focal choroidal excavation in patients with central serous chorioretinopathy.
AB - PURPOSE: To evaluate the prevalence and clinical features of focal choroidal
excavation (FCE) in patients presenting with central serous chorioretinopathy
(CSC). METHODS: This is a retrospective consecutive case series of consecutive
patients with CSC who were referred for spectral domain optical coherence
tomography (SD-OCT) between January 2010 and December 2011. Medical records were
reviewed and clinical features including presence of FCE in SD-OCT, fluorescence
angiography (FA), and indocyanine green angiography (ICGA) were studied. RESULTS:
Among the 116 CSC patients assessed, FCE was found in 11 eyes of 7 (6.0%)
patients. FCE was associated with subretinal fluid in six eyes of six patients
and serous pigment epithelial detachment in three eyes of two patients. The mean
central subfield retinal thickness of CSC eyes with FCE was 283.7 MUm, compared
with 377.5 MUm for CSC eyes without FCE (Mann-Whitney U-test, P=0.020). Five FCE
eyes of five patients had focal leakage on FA. Choroidal hyperpermeability on
ICGA was found in seven CSC eyes with FCE, with four eyes showing hypofluorescent
spot corresponding to the FCE. After a mean follow-up of 16 months, visual acuity
of all 11 eyes with FCE remained stable or improved at the last follow-up.
CONCLUSION: FCE is not an uncommon feature in patients with CSC and might be
associated with choroidal hemodynamic disturbances.
PMID- 25853405
TI - Hysteresis analysis and positioning control for a magnetic shape memory actuator.
AB - Magnetic shape memory alloys (MSM alloys), a new kind of smart materials, have
become a potential candidate in many engineering fields. MSMs have the advantage
of bearing a huge strain, much larger than other materials. In addition, they
also have fast response. These characteristics make MSM a good choice in micro
engineering. However, MSMs display the obvious hysteresis phenomenon of nonlinear
behavior. Thus the difficulty in using the MSM element as a positioning actuator
is increased due to the hysteresis. In this paper, the hysteresis phenomenon of
the MSM actuator is analyzed, and the closed-loop positioning control is also
implemented experimentally. For that, a modified fuzzy sliding mode control
(MFSMC) is proposed. The MFSMC and the PID control are used to design the
controllers for realizing the positioning control. The experimental results are
compared under different experimental conditions, such as different frequency,
amplitude, and loading. The experimental results show that the precise
positioning control of MFSMC can be achieved satisfactorily.
PMID- 25853404
TI - Experimental and numerical characterization of a hybrid Fabry-Perot cavity for
temperature sensing.
AB - A hybrid Fabry-Perot cavity sensing head based on a four-bridge microstructured
fiber is characterized for temperature sensing. The characterization of this
cavity is performed numerically and experimentally in the L-band. The sensing
head output signal presents a linear variation with temperature changes, showing
a sensitivity of 12.5 pm/ degrees C. Moreover, this Fabry-Perot cavity exhibits
good sensitivity to polarization changes and high stability over time.
PMID- 25853406
TI - Nonlinear optimization-based device-free localization with outlier link
rejection.
AB - Device-free localization (DFL) is an emerging wireless technique for estimating
the location of target that does not have any attached electronic device. It has
found extensive use in Smart City applications such as healthcare at home and
hospitals, location-based services at smart spaces, city emergency response and
infrastructure security. In DFL, wireless devices are used as sensors that can
sense the target by transmitting and receiving wireless signals collaboratively.
Many DFL systems are implemented based on received signal strength (RSS)
measurements and the location of the target is estimated by detecting the changes
of the RSS measurements of the wireless links. Due to the uncertainty of the
wireless channel, certain links may be seriously polluted and result in erroneous
detection. In this paper, we propose a novel nonlinear optimization approach with
outlier link rejection (NOOLR) for RSS-based DFL. It consists of three key
strategies, including: (1) affected link identification by differential RSS
detection; (2) outlier link rejection via geometrical positional relationship
among links; (3) target location estimation by formulating and solving a
nonlinear optimization problem. Experimental results demonstrate that NOOLR is
robust to the fluctuation of the wireless signals with superior localization
accuracy compared with the existing Radio Tomographic Imaging (RTI) approach.
PMID- 25853407
TI - Detection of steel fatigue cracks with strain sensing sheets based on large area
electronics.
AB - Reliable early-stage damage detection requires continuous monitoring over large
areas of structure, and with sensors of high spatial resolution. Technologies
based on Large Area Electronics (LAE) can enable direct sensing and can be scaled
to the level required for Structural Health Monitoring (SHM) of civil structures
and infrastructure. Sensing sheets based on LAE contain dense arrangements of
thin-film strain sensors, associated electronics and various control circuits
deposited and integrated on a flexible polyimide substrate that can cover large
areas of structures. This paper presents the development stage of a prototype
strain sensing sheet based on LAE for crack detection and localization. Two types
of sensing-sheet arrangements with size 6 * 6 inch (152 * 152 mm) were designed
and manufactured, one with a very dense arrangement of sensors and the other with
a less dense arrangement of sensors. The sensing sheets were bonded to steel
plates, which had a notch on the boundary, so the fatigue cracks could be
generated under cyclic loading. The sensors within the sensing sheet that were
close to the notch tip successfully detected the initialization of fatigue crack
and localized the damage on the plate. The sensors that were away from the crack
successfully detected the propagation of fatigue cracks based on the time history
of the measured strain. The results of the tests have validated the general
principles of the proposed sensing sheets for crack detection and identified
advantages and challenges of the two tested designs.
PMID- 25853408
TI - Sensing properties of Pd-loaded Co3O4 film for a ppb-level NO gas sensor.
AB - We prepared 0.1 wt%-30 wt% Pd-loaded Co3O4 by a colloidal mixing method and
investigated the sensing properties of a Pd-loaded Co3O4 sensor element, such as
the sensor response, 90% response time, 90% recovery time, and signal-to-noise
(S/N) ratio, toward low nitric oxide (NO) gas levels in the range from 50 to 200
parts per billion. The structural properties of the Pd-loaded Co3O4 powder were
investigated using X-ray diffraction analysis and transmission electron
microscopy. Pd in the powder existed as PdO. The sensor elements with 0.1 wt%-10
wt% Pd content have higher sensor properties than those without any Pd content.
The response of the sensor element with a 30 wt% Pd content decreased markedly
because of the aggregation and poor dispersibility of the PdO particles. High
sensor response and S/N ratio toward the NO gas were achieved when a sensor
element with 10 wt% Pd content was used.
PMID- 25853409
TI - The ethical importance of safety.
PMID- 25853410
TI - Cobalt(II) coordination polymer exhibiting single-ion-magnet-type field-induced
slow relaxation behavior.
AB - A one-dimensional cobalt(II) coordination polymer, [Co(btm)2(SCN)2.H2O]n [btm =
bis(1H-1,2,4-triazol-1-yl)methane], was synthesized and magnetically
characterized. The isolated slightly distorted octahedral Co(II) ion displays
field-induced slow relaxation with a big positive axial and a negative rhombic
magnetic anisotropy (D = 93.9 cm(-1) and E = -10.5 cm(-1)), and the anisotropy
energy barrier is 45.4 K.
PMID- 25853411
TI - Sequential push-pull pumping mechanism for washing and evacuation of an
immunoassay reaction chamber on a microfluidic CD platform.
AB - A centrifugal compact disc (CD) microfluidic platform with reservoirs, micro
channels, and valves can be employed for implementing a complete immunoassay.
Detection or biosensor chambers are either coated for immuno-interaction or a
biosensor chip is inserted in them. On microfluidic CDs featuring such multi-step
chemical/biological processes, the biosensor chamber must be repeatedly filled
with fluids such as enzymes solutions, buffers, and washing solutions. After each
filling step, the biosensor chamber needs to be evacuated by a passive siphoning
process to prepare it for the next step in the assay. However, rotational speed
dependency and limited space on a CD are two big obstacles to performing such
repetitive filling and siphoning steps. In this work, a unique thermo-pneumatic
(TP) Push-Pull pumping method is employed to provide a superior alternative
biosensor chamber filling and evacuation technique. The proposed technique is
demonstrated on two CD designs. The first design features a simple two-step
microfluidic process to demonstrate the evacuation technique, while the second
design shows the filling and evacuation technique with an example sequence for an
actual immunoassay. In addition, the performance of the filling and evacuation
technique as a washing step is also evaluated quantitatively and compared to the
conventional manual bench top washing method. The two designs and the performance
evaluation demonstrate that the technique is simple to implement, reliable, easy
to control, and allows for repeated push-pulls and thus filling and emptying of
the biosensor chamber. Furthermore, by addressing the issue of rotational speed
dependency and limited space concerns in implementing repetitive filling and
evacuation steps, this newly introduced technique increases the flexibility of
the microfluidic CD platform to perform multi-step biological and chemical
processes.
PMID- 25853413
TI - The evolutionary origins of the southern ocean Philobryid bivalves: hidden
biodiversity, ancient persistence.
AB - Philobryids (Bivalvia: Arcoida) are one of the most speciose marine bivalve
families in the Southern Ocean and are common throughout the Southern Hemisphere.
Considering this diversity and their brooding reproductive mode (limiting long
distance dispersal), this family may have been present in the Southern Ocean
since its inception. However Philobrya and Adacnarca appear only in the
Quaternary fossil record of the Antarctic, suggesting a much more recent
incursion. Molecular dating provides an independent means of measuring the time
of origin and radiation of this poorly known group. Here we present the first
combined molecular and morphological investigation of the Philobryidae in the
Southern Ocean. Two nuclear loci (18S and 28S) were amplified from 35 Southern
Ocean Adacnarca and Philobrya specimens, with a combined sequence length of 2,282
base pairs (bp). Adacnarca specimens (A. nitens and A. limopsoides) were resolved
as a strongly supported monophyletic group. Genus Philobrya fell into two
strongly supported groups ('sublaevis' and 'magellanica/wandelensis'),
paraphyletic with Adacnarca. The A. nitens species complex is identified as at
least seven morpho-species through morphological and genetic analysis of taxon
clustering. Phylogenetic analyses resolve Philobryidae as a strongly supported
monophyletic clade and sister taxon to the Limopsidae, as anticipated by their
classification into the superfamily Limopsoidea. Bayesian relaxed clock analyses
of divergence times suggest that genus Adacnarca radiated in the Southern Ocean
from the Early Paleogene, while P. sublaevis and P. wandelensis clades radiated
in the late Miocene, following the formation of the Antarctic Circumpolar
Current.
PMID- 25853412
TI - Phylogenetic molecular species delimitations unravel potential new species in the
pest genus Spodoptera Guenee, 1852 (Lepidoptera, Noctuidae).
AB - Nowadays molecular species delimitation methods promote the identification of
species boundaries within complex taxonomic groups by adopting innovative species
concepts and theories (e.g. branching patterns, coalescence). As some of them can
efficiently deal with large single-locus datasets, they could speed up the
process of species discovery compared to more time consuming molecular methods,
and benefit from the existence of large public datasets; these methods can also
particularly favour scientific research and actions dealing with threatened or
economically important taxa. In this study we aim to investigate and clarify the
status of economically important moths species belonging to the genus Spodoptera
(Lepidoptera, Noctuidae), a complex group in which previous phylogenetic analyses
and integrative approaches already suggested the possible occurrence of cryptic
species and taxonomic ambiguities. In this work, the effectiveness of innovative
(and faster) species delimitation approaches to infer putative species boundaries
has been successfully tested in Spodoptera, by processing the most comprehensive
dataset (in terms of number of species and specimens) ever achieved; results are
congruent and reliable, irrespective of the set of parameters and phylogenetic
models applied. Our analyses confirm the existence of three potential new species
clusters (for S. exigua (Hubner, 1808), S. frugiperda (J.E. Smith, 1797) and S.
mauritia (Boisduval, 1833)) and support the synonymy of S. marima (Schaus, 1904)
with S. ornithogalli (Guenee, 1852). They also highlight the ambiguity of the
status of S. cosmiodes (Walker, 1858) and S. descoinsi Lalanne-Cassou & Silvain,
1994. This case study highlights the interest of molecular species delimitation
methods as valuable tools for species discovery and to emphasize taxonomic
ambiguities.
PMID- 25853414
TI - Correction: prevalence and risk factors of anaemia among children aged between 6
months and 14 years in Kenya.
AB - [This corrects the article DOI: 10.1371/journal.pone.0113756.].
PMID- 25853416
TI - Back to the roots: the integration of a constructed wetland into a recirculating
hatchery - a case study.
AB - Aquaculture is currently one of the fastest growing food-producing sectors,
accounting for around 50% of the world's food fish. Limited resources, together
with climatic change, have stimulated the search for solutions to support and
sustain the production of fish as a nutritious food. The integration of a
constructed wetland (CW) into a recirculating hatchery (RHS) was evaluated with
respect to its economic feasibility and environmental impact. The outcome of
eight production cycles showed the potential of CW integration for expanded
production without increased operation costs or environmental load. Concretely,
the use of constructed wetland allows the rearing about 40% more fish biomass,
resulting in higher production and profitability. The low requirements for space,
fresh water, and energy enable the establishment of such systems almost anywhere.
Constructed wetlands could enhance the productivity of existing small scale
facilities, as well as larger systems, to address economic and environmental
issues in aquaculture. Such systems have potential to be sustainable in the
context of possible future climate change and resource limitations.
PMID- 25853417
TI - Alternating antibiotics render resistant bacteria beatable.
PMID- 25853415
TI - Domain-swapped dimer of Pseudomonas aeruginosa cytochrome c551: structural
insights into domain swapping of cytochrome c family proteins.
AB - Cytochrome c (cyt c) family proteins, such as horse cyt c, Pseudomonas aeruginosa
cytochrome c551 (PA cyt c551), and Hydrogenobacter thermophilus cytochrome c552
(HT cyt c552), have been used as model proteins to study the relationship between
the protein structure and folding process. We have shown in the past that horse
cyt c forms oligomers by domain swapping its C-terminal helix, perturbing the Met
heme coordination significantly compared to the monomer. HT cyt c552 forms dimers
by domain swapping the region containing the N-terminal alpha-helix and heme,
where the heme axial His and Met ligands belong to different protomers. Herein,
we show that PA cyt c551 also forms domain-swapped dimers by swapping the region
containing the N-terminal alpha-helix and heme. The secondary structures of the
M61A mutant of PA cyt c551 were perturbed slightly and its oligomer formation
ability decreased compared to that of the wild-type protein, showing that the
stability of the protein secondary structures is important for domain swapping.
The hinge loop of domain swapping for cyt c family proteins corresponded to the
unstable region specified by hydrogen exchange NMR measurements for the monomer,
although the swapping region differed among proteins. These results show that the
unstable loop region has a tendency to become a hinge loop in domain-swapped
proteins.
PMID- 25853418
TI - Reduced adolescent-age spatial learning ability associated with elevated juvenile
age superoxide levels in complex I mouse mutants.
AB - Large-scale, heteroplasmic and generally pathogenic mtDNA defects (as induced by
defective mitochondrial DNA polymerase, clonal mutations or DNA deletions) are
known to negatively impact on life span and can result in apoptosis and tissue
loss in, e.g., skeletal muscle or reduce learning abilities. The functional
impact of homoplasmic specific mtDNA point mutations, e.g., in genes coding for
the electron transport chain, however, remains a matter of debate. The present
study contributes to this discussion and provides evidence that a single point
mutation in complex I of the respiratory chain is associated with impairment of
spatial navigation in adolescent (6-month-old) mice, i.e., reduced performance in
the Morris Water Maze, which goes along with increased production of reactive
oxygen species (ROS) in juvenile mice (3 months) but not at the age of phenotype
expression. A point mutation in complex III goes along with only a mild and non
significant negative effect on cognitive performance and no significant changes
in ROS production. These findings suggest to also consider the ontogenetic
development of phenotypes when studying mtDNA mutations and highlights a possible
impact of complex I dysfunction on the emergence of neurological deficits.
PMID- 25853420
TI - Analysis of the Causes of Failed Antireflux Surgery and the Principles of
Treatment: A Review.
AB - IMPORTANCE: Although the diagnostic evaluation and technical elements for a
successful laparoscopic fundoplication have been clearly identified, 10% to 20%
of patients will eventually experience recurrence of their symptoms. The
management of patients who fail antireflux surgery is complex and not well
codified. OBJECTIVE: To provide an evidence- and experience-based analysis of the
causes of failed antireflux surgery and to underscore the principles of
treatment. EVIDENCE REVIEW: PubMed was searched for articles published between
1980 and 2014. The search terms included were the following: heartburn,
regurgitation, dysphagia, gastroesophageal reflux disease, cough, aspiration,
laryngitis, GERD, GORD, endoscopy, manometry, pH monitoring, proton pump
inhibitors, and Nissen fundoplication. FINDINGS: Before planning therapy, a
careful workup is necessary to determine whether the symptoms are due to
recurrent reflux and to understand what caused the recurrence. Subsequently,
therapy needs to be individualized based on the symptoms and on the findings of
the workup. In some patients, a nonesophageal cause will be identified. Among
patients with recurrent reflux, some will do well with acid-reducing medications
and others will need another operation. CONCLUSIONS AND RELEVANCE: Laparoscopic
antireflux surgery is a very effective and long-lasting treatment for
gastroesophageal reflux disease. Its success is based on a careful preoperative
evaluation and on the performance of a fundoplication that respects the key
technical elements. Patients who are still symptomatic postoperatively must be
thoroughly evaluated to identify the cause of failure, and treatment must be
individualized.
PMID- 25853419
TI - Modulation of sweet taste by umami compounds via sweet taste receptor subunit
hT1R2.
AB - Although the five basic taste qualities-sweet, sour, bitter, salty and umami-can
be recognized by the respective gustatory system, interactions between these
taste qualities are often experienced when food is consumed. Specifically, the
umami taste has been investigated in terms of whether it enhances or reduces the
other taste modalities. These studies, however, are based on individual
perception and not on a molecular level. In this study we investigated umami
sweet taste interactions using umami compounds including monosodium glutamate
(MSG), 5'-mononucleotides and glutamyl-dipeptides, glutamate-glutamate (Glu-Glu)
and glutamate-aspartic acid (Glu-Asp), in human sweet taste receptor hT1R2/hT1R3
expressing cells. The sensitivity of sucrose to hT1R2/hT1R3 was significantly
attenuated by MSG and umami active peptides but not by umami active nucleotides.
Inhibition of sweet receptor activation by MSG and glutamyl peptides is obvious
when sweet receptors are activated by sweeteners that target the extracellular
domain (ECD) of T1R2, such as sucrose and acesulfame K, but not by cyclamate,
which interact with the T1R3 transmembrane domain (TMD). Application of umami
compounds with lactisole, inhibitory drugs that target T1R3, exerted a more
severe inhibitory effect. The inhibition was also observed with F778A sweet
receptor mutant, which have the defect in function of T1R3 TMD. These results
suggest that umami peptides affect sweet taste receptors and this interaction
prevents sweet receptor agonists from binding to the T1R2 ECD in an allosteric
manner, not to the T1R3. This is the first report to define the interaction
between umami and sweet taste receptors.
PMID- 25853421
TI - EBNA2 binds to genomic intervals associated with multiple sclerosis and overlaps
with vitamin D receptor occupancy.
AB - Epstein-Barr virus (EBV) is a non-heritable factor that associates with multiple
sclerosis (MS). However its causal relationship with the disease is still
unclear. The virus establishes a complex co-existence with the host that includes
regulatory influences on gene expression. Hence, if EBV contributes to the
pathogenesis of MS it may do so by interacting with disease predisposing genes.
To verify this hypothesis we evaluated EBV nuclear antigen 2 (EBNA2, a protein
that recent works by our and other groups have implicated in disease development)
binding inside MS associated genomic intervals. We found that EBNA2 binding
occurs within MS susceptibility sites more than expected by chance (factor of
observed vs expected overlap [O/E] = 5.392-fold, p < 2.0e-05). This remains
significant after controlling for multiple genomic confounders. We then asked
whether this observation is significant per se or should also be viewed in the
context of other disease relevant gene-environment interactions, such as those
attributable to vitamin D. We therefore verified the overlap between EBNA2
genomic occupancy and vitamin D receptor (VDR) binding sites. EBNA2 shows a
striking overlap with VDR binding sites (O/E = 96.16-fold, p < 2.0e-05), even
after controlling for the chromatin accessibility state of shared regions (p
<0.001). Furthermore, MS susceptibility regions are preferentially targeted by
both EBNA2 and VDR than by EBNA2 alone (enrichment difference = 1.722-fold, p =
0.0267). Taken together, these findings demonstrate that EBV participates in the
gene-environment interactions that predispose to MS.
PMID- 25853422
TI - Clinical evaluation of a loop-mediated isothermal amplification (LAMP) assay for
rapid detection of Neisseria meningitidis in cerebrospinal fluid.
AB - BACKGROUND: Neisseria meningitidis (Nm) is a leading causative agent of bacterial
meningitis in humans. Traditionally, meningococcal meningitis has been diagnosed
by bacterial culture. However, isolation of bacteria from patients' cerebrospinal
fluid (CSF) is time consuming and sometimes yields negative results. Recently,
polymerase chain reaction (PCR)-based diagnostic methods of detecting Nm have
been considered the gold standard because of their superior sensitivity and
specificity compared with culture. In this study, we developed a loop-mediated
isothermal amplification (LAMP) method and evaluated its ability to detect Nm in
cerebrospinal fluid (CSF). METHODOLOGY/PRINCIPAL FINDINGS: We developed a
meningococcal LAMP assay (Nm LAMP) that targets the ctrA gene. The primer
specificity was validated using 16 strains of N. meningitidis (serogroup A, B, C,
D, 29-E, W-135, X, Y, and Z) and 19 non-N. meningitidis species. Within 60 min,
the Nm LAMP detected down to ten copies per reaction with sensitivity 1000-fold
more than that of conventional PCR. The LAMP assays were evaluated using a set of
1574 randomly selected CSF specimens from children with suspected meningitis
collected between 1998 and 2002 in Vietnam, China, and Korea. The LAMP method was
shown to be more sensitive than PCR methods for CSF samples (31 CSF samples were
positive by LAMP vs. 25 by PCR). The detection rate of the LAMP method was
substantially higher than that of the PCR method. In a comparative analysis of
the PCR and LAMP assays, the clinical sensitivity, specificity, positive
predictive value, and negative predictive value of the LAMP assay were 100%,
99.6%, 80.6%, and 100%, respectively. CONCLUSIONS/SIGNIFICANCE: Compared to PCR,
LAMP detected Nm with higher analytical and clinical sensitivity. This sensitive
and specific LAMP method offers significant advantages for screening patients on
a population basis and for diagnosis in clinical settings.
PMID- 25853423
TI - Inequalities in maternal health care utilization in sub-Saharan African
countries: a multiyear and multi-country analysis.
AB - To assess social inequalities in the use of antenatal care (ANC), facility based
delivery (FBD), and modern contraception (MC) in two contrasting groups of
countries in sub-Saharan Africa divided based on their progress towards maternal
mortality reduction. Six countries were included in this study. Three countries
(Ethiopia, Madagascar, and Uganda) had <350 MMR in 2010 with >4.5% average annual
reduction rate while another three (Cameroon, Zambia, and Zimbabwe) had >550 MMR
in 2010 with only <1.5% average annual reduction rate. All of these countries had
at least three rounds of Demographic and Health Surveys (DHS) before 2012. We
measured rate ratios and differences, as well as relative and absolute
concentration indices in order to examine within-country geographical and wealth
based inequalities in the utilization of ANC, FBD, and MC. In the countries which
have made sufficient progress (i.e. Ethiopia, Madagascar, and Uganda), ANC use
increased by 8.7, 9.3 and 5.7 percent, respectively, while the utilization of FBD
increased by 4.7, 0.7 and 20.2 percent, respectively, over the last decade. By
contrast, utilization of these services either plateaued or decreased in
countries which did not make progress towards reducing maternal mortality, with
the exception of Cameroon. Utilization of MC increased in all six countries but
remained very low, with a high of 40.5% in Zimbabwe and low of 16.1% in Cameroon
as of 2011. In general, relative measures of inequalities were found to have
declined overtime in countries making progress towards reducing maternal
mortality. In countries with insufficient progress towards maternal mortality
reduction, these indicators remained stagnant or increased. Absolute measures for
geographical and wealth-based inequalities remained high invariably in all six
countries. The increasing trend in the utilization of maternal care services was
found to concur with a steady decline in maternal mortality. Relative inequality
declined overtime in countries which made progress towards reducing maternal
mortality.
PMID- 25853424
TI - Peripheral blood mononuclear cells HIV DNA levels impact intermittently on
neurocognition.
AB - OBJECTIVES: To determine the contribution of peripheral blood mononuclear cells'
(PBMCs) HIV DNA levels to HIV-associated dementia (HAD) and non-demented HIV
associated neurocognitive disorders (HAND) in chronically HIV-infected adults
with long-term viral suppression on combined antiretroviral treatment (cART).
METHODS: Eighty adults with chronic HIV infection on cART (>97% with plasma and
CSF HIV RNA <50 copies/mL) were enrolled into a prospective observational cohort
and underwent assessments of neurocognition and pre-morbid cognitive ability at
two visits 18 months apart. HIV DNA in PBMCs was measured by real-time PCR at the
same time-points. RESULTS: At baseline, 46% had non-demented HAND; 7.5% had HAD.
Neurocognitive decline occurred in 14% and was more likely in those with HAD
(p<.03). Low pre-morbid cognitive ability was uniquely associated with HAD
(p<.05). Log10 HIV DNA copies were stable between study visits (2.26 vs. 2.22 per
106 PBMC). Baseline HIV DNA levels were higher in those with lower pre-morbid
cognitive ability (p<.04), and higher in those with no ART treatment during HIV
infection 1st year (p = .03). Baseline HIV DNA was not associated with overall
neurocognition. However, % ln HIV DNA change was associated with decline in
semantic fluency in unadjusted and adjusted analyses (p = .01-.03), and motor
coordination (p = .02-.12) to a lesser extent. CONCLUSIONS: PBMC HIV DNA plays a
role in HAD pathogenesis, and this is moderated by pre-morbid cognitive ability
in the context of long-term viral suppression. While the HIV DNA levels in PBMC
are not associated with current non-demented HAND, increasing HIV DNA levels were
associated with a decline in neurocognitive functions associated with HAND
progression.
PMID- 25853425
TI - Correction: a tale of two recent spills-comparison of 2014 Galveston Bay and 2010
Deepwater Horizon Oil Spill Residues.
AB - [This corrects the article DOI: 10.1371/journal.pone.0118098.].
PMID- 25853426
TI - Abundant genetic overlap between blood lipids and immune-mediated diseases
indicates shared molecular genetic mechanisms.
AB - Epidemiological studies suggest a relationship between blood lipids and immune
mediated diseases, but the nature of these associations is not well understood.
We used genome-wide association studies (GWAS) to investigate shared single
nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated
diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False
Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid
levels [triglycerides (TG), low density lipoproteins (LDL), high density
lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases
(Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes,
celiac disease, psoriasis and sarcoidosis). We found significant polygenic
pleiotropy between the blood lipids and all the investigated immune-mediated
diseases. We discovered several shared risk loci between the immune-mediated
diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses
differentiated the pattern of pleiotropy among the immune-mediated diseases. The
new pleiotropic loci increased the number of functional gene network nodes
representing blood lipid loci by 40%. Pathway analyses implicated several novel
shared mechanisms for immune pathogenesis and lipid biology, including
glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions
(e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune
mediated diseases independent of environmental factors. Our findings provide
novel mechanistic insights into dyslipidemia and immune-mediated diseases and may
have implications for therapeutic trials involving lipid-lowering and anti
inflammatory agents.
PMID- 25853427
TI - A novel pore-forming toxin in type A Clostridium perfringens is associated with
both fatal canine hemorrhagic gastroenteritis and fatal foal necrotizing
enterocolitis.
AB - A role for type A Clostridium perfringens in acute hemorrhagic and necrotizing
gastroenteritis in dogs and in necrotizing enterocolitis of neonatal foals has
long been suspected but incompletely characterized. The supernatants of an
isolate made from a dog and from a foal that died from these diseases were both
found to be highly cytotoxic for an equine ovarian (EO) cell line. Partial genome
sequencing of the canine isolate revealed three novel putative toxin genes
encoding proteins related to the pore-forming Leukocidin/Hemolysin Superfamily;
these were designated netE, netF, and netG. netE and netF were located on one
large conjugative plasmid, and netG was located with a cpe enterotoxin gene on a
second large conjugative plasmid. Mutation and complementation showed that only
netF was associated with the cytotoxicity. Although netE and netG were not
associated with cytotoxicity, immunoblotting with specific antisera showed these
proteins to be expressed in vitro. There was a highly significant association
between the presence of netF with type A strains isolated from cases of canine
acute hemorrhagic gastroenteritis and foal necrotizing enterocolitis. netE and
netF were found in all cytotoxic isolates, as was cpe, but netG was less
consistently present. Pulsed-field gel electrophoresis showed that netF-positive
isolates belonged to a clonal population; some canine and equine netF-positive
isolates were genetically indistinguishable. Equine antisera to recombinant Net
proteins showed that only antiserum to rNetF had high supernatant cytotoxin
neutralizing activity. The identifica-tion of this novel necrotizing toxin is an
important advance in understanding the virulence of type A C. perfringens in
specific enteric disease of animals.
PMID- 25853428
TI - Antioxidant and angiostatic effect of Spirulina platensis suspension in complete
Freund's adjuvant-induced arthritis in rats.
AB - BACKGROUND: Currently, natural products have built a well-recognized role in the
management of many degenerative diseases, mainly rheumatoid arthritis. Recent
studies suggest that Spirulina, a unicellular blue-green alga, may have a variety
of health benefits and curative properties and is also competent of acting as an
anti-inflammatory, antioxidant and recently anti-angiogenic agent. In the present
study, the antioxidant and the immunomodulatory effect of Spirulina platensis as
well as its anti-angiogenic effect against complete Freund's adjuvant-induced
arthritis (AIA) in rat model were tested. RESULTS: We found that the development
of arthritis was concealed; moreover it successfully inhibited the development of
macroscopic as well as microscopic and histopathological lesions in AIA rats when
compared to control. Spirulina treated group showed a higher survival rate and
moreover, it reduced the clinical score of RA in a dose dependent manner.
Furthermore, Spirulina decreased serum levels of COX-2, TNF-alpha, IL-6, TBARS,
VEGF and increased serum levels of GSH compared to the RA non-treated group.
CONCLUSIONS: The present study concluded that Spirulina is able to restrain the
changes produced through adjuvant-induced arthritis. The suppressing effect of
Spirulina could be attributed, at least in part, to anti-inflammatory,
antioxidant and anti-angiogenic properties.
PMID- 25853429
TI - Testing pancreatic islet function at the single cell level by calcium influx with
associated marker expression.
AB - Studying the response of islet cells to glucose stimulation is important for
understanding cell function in healthy and disease states. Most functional assays
are performed on whole islets or cell populations, resulting in averaged
observations and loss of information at the single cell level. We demonstrate
methods to examine calcium fluxing in individual cells of intact islets in
response to multiple glucose challenges. Wild-type mouse islets predominantly
contained cells that responded to three (out of three) sequential high glucose
challenges, whereas cells of diabetic islets (db/db or NOD) responded less
frequently or not at all. Imaged islets were also immunostained for endocrine
markers to associate the calcium flux profile of individual cells with gene
expression. Wild-type mouse islet cells that robustly fluxed calcium expressed
beta cell markers (INS/NKX6.1), whereas islet cells that inversely fluxed at low
glucose expressed alpha cell markers (GCG). Diabetic mouse islets showed a higher
proportion of dysfunctional beta cells that responded poorly to glucose
challenges. Most of the failed calcium influx responses in beta cells were
observed in the second and third high glucose challenges, emphasizing the
importance of multiple sequential glucose challenges for assessing the full
function of islet cells. Human islet cells were also assessed and showed
functional alpha and beta cells. This approach to analyze islet responses to
multiple glucose challenges in correlation with gene expression assays expands
the understanding of beta cell function and the diseased state.
PMID- 25853430
TI - A water-stable lanthanide-functionalized MOF as a highly selective and sensitive
fluorescent probe for Cd(2.).
AB - A highly selective and sensitive fluorescent sensor for Cd(2+) in aqueous
solution based on a lanthanide post-functionalized metal-organic framework was
developed.
PMID- 25853431
TI - Coupling between Pentachlorophenol Dechlorination and Soil Redox As Revealed by
Stable Carbon Isotope, Microbial Community Structure, and Biogeochemical Data.
AB - Carbon isotopic analysis and molecular-based methods were used in conjunction
with geochemical data sets to assess the dechlorination of pentachlorophenol
(PCP) when coupled to biogeochemical processes in a mangrove soil having no prior
history of anthropogenic contamination. The PCP underwent 96% dechlorination in
soil amended with acetate, compared to 21% dehalogenation in control soil. Carbon
isotope analysis of residual PCP demonstrated an obvious enrichment of 13C
(epsilonC, -3.01+/-0.1%). Molecular and statistical analyses demonstrated that
PCP dechlorination and Fe(III) reduction were synergistically combined electron
accepting processes. Microbial community analysis further suggested that enhanced
dechlorination of PCP during Fe(III) reduction was mediated by members of the
multifunctional family of Geobacteraceae. In contrast, PCP significantly
suppressed the growth of SO4(2-) reducers, which, in turn, facilitated the
production of CH4 by diversion of electrons from SO4(2-) reduction to
methanogenesis. The integrated data regarding stoichiometric alterations in this
study gives direct evidence showing PCP, Fe(III), and SO4(2-) reduction, and CH4
production are coupled microbial processes during changes in soil redox.
PMID- 25853432
TI - Practice explains abolished behavioural adaptation after human dorsal anterior
cingulate cortex lesions.
AB - The role of mid-cingulate cortex (MCC), also referred to as dorsal anterior
cingulate cortex, in regulating cognitive control is a topic of primary
importance in cognitive neuroscience. Although many studies have shown that MCC
responds to cognitive demands, lesion studies in humans are inconclusive
concerning the causal role of the MCC in the adaptation to these demands. By
elegantly combining single-cell recordings with behavioural methods, Sheth et al.
[Sheth, S. et al. Human dorsal anterior cingulate cortex neurons mediate ongoing
behavioural adaptation. Nature 488, 218-22 (2012).] recently were able to show
that neurons in MCC encode cognitive demand. Importantly, this study also claimed
that focal lesions of the MCC abolished behavioural adaptation to cognitive
demands. Here we show that the absence of post-cingulotomy behavioural adaptation
reported in this study may have been due to practice effects. We run a control
condition where we tested subjects before and after a dummy treatment, which
substituted cingulotomy with a filler task (presentation of a documentary). The
results revealed abolished behavioural adaptation following the dummy treatment.
Our findings suggest that future work using proper experimental designs is needed
to advance the understanding of the causal role of the MCC in behavioural
adaptation.
PMID- 25853434
TI - Pdots, a new type of nanoparticle, bind to mTHPC via their lipid modified surface
and exhibit very high FRET efficiency between the core and the sensitizer.
AB - Pdots are a new type of nanoparticle which exhibit strong potential for future
applications in biophysics and cell biology. They are composed of organic
chromophoric polymers, whose surfaces can be modified with different amphiphilic
polymers, such as PEGylated lipids to make them very stable as colloids in water.
We demonstrate in this manuscript that the lipid nano-coating around the Pdot can
bind very efficiently to amphiphilic molecules, such as photosensitizers e.g.
meso-tetrahydroxyphenylchlorin (mTHPC). As a result the sensitizer is brought
into very close contact with the cores of the Pdots, and resonance energy
transfer from the core to the sensitizer is very efficient; in some cases it is
close to 1. We show the spectroscopic properties of two types of Pdots; their
sizes, which are in the 13-47 nm range, depend on the kind of polymer and the
length of the PEGylated lipid chains that wrap it. We measured the efficiency of
FRET by investigating the decrease in donor intensity or its lifetime upon
binding with mTHPC. We also show the relative yields of singlet oxygen that are
obtained via two pathways: by exciting the Pdots which transfer the energy to the
attached sensitizer, or by exciting the sensitizer directly. This methodology
could be used to enhance the use of a photosensitizer by employing both pathways
in parallel.
PMID- 25853433
TI - Deleterious effects of endocrine disruptors are corrected in the mammalian
germline by epigenome reprogramming.
AB - BACKGROUND: Exposure to environmental endocrine-disrupting chemicals during
pregnancy reportedly causes transgenerationally inherited reproductive defects.
We hypothesized that to affect the grandchild, endocrine-disrupting chemicals
must alter the epigenome of the germ cells of the in utero-exposed G1 male fetus.
Additionally, to affect the great-grandchild, the aberration must persist in the
germ cells of the unexposed G2 grandchild. RESULTS: Here, we treat gestating
female mice with vinclozolin, bisphenol A, or di-(2-ethylhexyl)phthalate during
the time when global de novo DNA methylation and imprint establishment occurs in
the germ cells of the G1 male fetus. We map genome-wide features in purified G1
and G2 prospermatogonia, in order to detect immediate and persistent epigenetic
aberrations, respectively. We detect changes in transcription and methylation in
the G1 germline immediately after endocrine-disrupting chemicals exposure, but
changes do not persist into the G2 germline. Additional analysis of genomic
imprints shows no persistent aberrations in DNA methylation at the differentially
methylated regions of imprinted genes between the G1 and G2 prospermatogonia, or
in the allele-specific transcription of imprinted genes between the G2 and G3
soma. CONCLUSIONS: Our results suggest that endocrine-disrupting chemicals exert
direct epigenetic effects in exposed fetal germ cells, which are corrected by
reprogramming events in the next generation. Avoiding transgenerational
inheritance of environmentally-caused epigenetic aberrations may have played an
evolutionary role in the development of dual waves of global epigenome
reprogramming in mammals.
PMID- 25853435
TI - ABHD4 regulates multiple classes of N-acyl phospholipids in the mammalian central
nervous system.
AB - N-Acyl phospholipids are atypical components of cell membranes that bear three
acyl chains and serve as potential biosynthetic precursors for lipid mediators
such as endocannabinoids. Biochemical studies have implicated ABHD4 as a brain N
acyl phosphatidylethanolamine (NAPE) lipase, but in vivo evidence for this
functional assignment is lacking. Here, we describe ABHD4(-/-) mice and their
characterization using untargeted lipidomics to discover that ABHD4 regulates
multiple classes of brain N-acyl phospholipids. In addition to showing reductions
in brain glycerophospho-NAEs (GP-NAEs) and plasmalogen-based lyso-NAPEs (lyso
pNAPEs), ABHD4(-/-) mice exhibited decreases in a distinct set of brain lipids
that were structurally characterized as N-acyl lysophosphatidylserines (lyso
NAPSs). Biochemical assays confirmed that NAPS lipids are direct substrates of
ABHD4. These findings, taken together, designate ABHD4 as a principal regulator
of N-acyl phospholipid metabolism in the mammalian nervous system.
PMID- 25853436
TI - An anti-B7-H4 antibody-drug conjugate for the treatment of breast cancer.
AB - B7-H4 has been implicated in cancers of the female reproductive system and
investigated for its possible use as a biomarker for cancer, but there are no
preclinical studies to demonstrate that B7-H4 is a molecular target for
therapeutic intervention of cancer. We provide evidence that the prevalence and
expression levels of B7-H4 are high in different subtypes of breast cancer and
that only a few normal tissues express B7-H4 on the cell membrane. These profiles
of low normal expression and upregulation in cancer provide an opportunity for
the use of antibody-drug conjugates (ADCs), cytotoxic drugs chemically linked to
antibodies, for the treatment of B7-H4 positive cancers. We have developed an ADC
specific to B7-H4 that uses a linker drug consisting of a potent antimitotic,
monomethyl auristatin E (MMAE), linked to engineered cysteines (THIOMAB) via a
protease labile linker. We will refer to ADCs that use the THIOMAB format as TDCs
to help distinguish the format from standard MC-vc-MMAE ADCs that are conjugated
to the interchain disulfide bonds. Anti-B7-H4 (h1D11)-MC-vc-PAB-MMAE (h1D11 TDC)
produced durable tumor regression in cell line and patient-derived xenograft
models of triple-negative breast cancer. It also binds rat B7-H4 with similar
affinity to human and allowed us to test for target dependent toxicity in rats.
We found that our anti-B7-H4 TDC has toxicity findings similar to untargeted TDC.
Our results validate B7-H4 as an ADC target for breast cancer and support the
possible use of this TDC in the treatment of B7-H4(+) breast cancer.
PMID- 25853437
TI - Outpatient Cervical and Lumbar Spine Surgery is Feasible and Safe: A Consecutive
Single Center Series of 1449 Patients.
AB - BACKGROUND: There is an increasing demand for surgery of degenerative spinal
disease. Limited healthcare resources draw attention to the need for cost
effective treatments. Outpatient surgery, when safe and feasible, is more cost
effective than inpatient surgery. OBJECTIVE: To study types and rates of
complications after outpatient lumbar and cervical spine decompressions. METHODS:
Complications were recorded prospectively in 1449 (1073 lumbar, 376 cervical)
outpatients undergoing microsurgical decompression for degenerative spinal
disease at the private Oslofjord Clinic from 2008 to 2013. RESULTS: Surgical
mortality was 0%. A total of 51 (3.5%) minor and major complications were
recorded in 51 patients. Three (0.2%) patients had to be admitted to a hospital
the day of surgery. Twenty-two (1.5%) patients were admitted to a hospital within
3 months due to surgery-related events. The encountered complications were
postoperative hematoma (0.6%), neurological deterioration (0.3%), deep wound
infection (0.9%), dural lesions with cerebrospinal fluid leakage (1.0%),
persistent dysphagia (0.1%), persistent hoarseness (0.1%), and severe
pain/headache (0.4%). All of the life-threatening hematomas were detected within
6 and 3 hours after cervical and lumbar surgery, respectively. CONCLUSION: This
series of 1449 consecutive outpatient microsurgical spine decompressions adds to
the growing literature in favor of outpatient spinal surgery in properly selected
patients. In our study, 99.8% of the patients were successfully discharged either
to their homes or to a hotel on the day of surgery. The overall complication rate
was 3.5%, surgical mortality was 0%, and only 1.5% had to be admitted to a
hospital within 3 months after surgery.
PMID- 25853438
TI - Size-optimized galactose-capped gold nanoparticles for the colorimetric detection
of heat-labile enterotoxin at nanomolar concentrations.
AB - The development of a galactose-capped gold nanoparticle-based colorimetric sensor
for the detection of the lectin heat-labile enterotoxin is reported. Heat-labile
enterotoxin is one of the pathogenic agents responsible for the intestinal
disease called 'traveller's diarrhoea'. By means of specific interaction between
galactose moieties attached to the surface of gold nanoparticles and receptors on
the B-subunit of heat-labile enterotoxin (LTB), the gold nanoparticles reported
here act as an efficient colorimetric sensor, which can detect the toxin at
nanomolar concentrations. The effect of gold nanoparticle size on the detection
sensitivity was investigated in detail. Amongst the various sizes of gold
nanoparticles studied (2, 7, 12, and 20 nm), the 12 nm sized gold nanoparticles
were found to be the most efficient, with a minimum heat-labile enterotoxin
detection concentration of 100 nM. The red to purple colour change of the gold
nanoparticle solution occurred within two minutes, indicating rapid toxin
sensing.
PMID- 25853439
TI - Plasmon enhancement of luminescence upconversion.
AB - Frequency conversion has always been an important topic in optics. Nonlinear
optics has traditionally focused on frequency conversion based on nonlinear
susceptibility but with the recent development of upconversion nanomaterials,
luminescence upconversion has begun to receive renewed attention. While
upconversion nanomaterials open doors to a wide range of new opportunities, they
remain too inefficient for most applications. Incorporating plasmonic
nanostructures provides a promising pathway to highly efficient upconversion.
Naturally, a plethora of theoretical and experimental studies have been published
in recent years, reporting enhancements up to several hundred. It is however
difficult to make meaningful comparisons since the plasmonic fields are highly
sensitive to the local geometry and excitation condition. Also, many luminescence
upconversion processes involve multiple steps via different physical mechanisms
and the overall output is often determined by a delicate interplay among them.
This review is aimed at offering a comprehensive framework for plasmon enhanced
luminescence upconversion. We first present quantum electrodynamics descriptions
for all the processes involved in luminescence upconversion, which include
absorption, emission, energy transfer and nonradiative transitions. We then
present a bird's eye view of published works on plasmon enhanced upconversion,
followed by more detailed discussion on comparable classes of nanostructures, the
effects of spacer layers and local heating, and the dynamics of the plasmon
enhanced upconversion process. Plasmon enhanced upconversion is a challenging and
exciting field from the fundamental scientific perspective and also from
technological standpoints. It offers an excellent system to study how optical
processes are affected by the local photonic environment. This type of research
is particularly timely as the plasmonics is placing heavier emphasis on
nonlinearity. At the same time, efficient upconversion could make a significant
impact on many applications including solar energy conversion and biomedical
imaging. The marriage of luminescent materials research with nanophotonics
currently being initiated with plasmon enhanced upconversion research explores a
new frontier in photonics that could potentially spawn many exciting new fields.
PMID- 25853440
TI - Selectfluor-Promoted Sequential Reactions via Allene Intermediates: Metal-Free
Construction of Fused Polycyclic Skeletons.
AB - Polycyclic skeletons are present in numerous important compounds, such as
synthetic intermediates and target molecules of biological interest. In this
paper, a Selectfluor-promoted construction of polycyclic skeletons with high
synthetic efficiency was developed.
PMID- 25853441
TI - Comparision of surgical outcomes of intraocular lens refixation and intraocular
lens exchange with perfluorocarbon liquid and fibrin glue-assisted sutureless
scleral fixation.
AB - AIM: The purpose of this study was to compare the surgical outcomes of
intraocular lens (IOL) refixation with intraocular lens exchange using
perfluorocarbon liquid (PFCL) and fibrin glue-assisted sutureless scleral
fixation surgery in patients with dislocation of the IOL. METHODS: Twenty-five
eyes of 25 patients who underwent surgery for dislocated IOLs with PFCL and
fibrin glue-assisted scleral fixation were studied; 13 eyes experienced IOL
refixation (in-the-bag and out-of-the-bag), and 12 eyes experienced IOL exchange.
Preoperative and postoperative clinical features from patient charts and 25 eyes
with >6 months' follow-up information were reviewed and analyzed. RESULTS: At
postoperative 6 months, best-corrected visual acuity (BCVA) and spherical
equivalent of IOL refixation and exchange were significantly improved (P=0.042,
P=0.001), and endothelial cell density was significantly decreased in the two
groups with no significant difference between them. Surgically induced
astigmatism of IOL refixation improved from 0.90+/-0.47 to 0.61+/-0.37 (P=0.012),
and IOL exchange improved from 1.17+/-0.64 to 0.73+/-0.37 (P=0.037) at
postoperative 6 months, with no significant difference between the two groups.
Complications occurred in four eyes in the IOL refixation group and in three eyes
in the IOL exchange group. CONCLUSION: PFCL and fibrin glue-assisted IOL
sutureless scleral refixation or exchanged fixation was an effective surgical
treatment for IOL dislocation. Also, because postoperative BCVA, surgical
outcomes, and complications did not differ significantly between IOL refixation
and exchange surgery, if IOL exchange surgery is not indicated, IOL refixation
surgical techniques should be considered.
PMID- 25853443
TI - Incidence and indications for pars plana vitrectomy following the treatment of
posterior uveal melanomas in Scotland.
AB - BACKGROUND: Globe-sparing treatments such as plaque brachytherapy, local or
endoresection, and proton beam therapy (PBT) are the treatments of choice for
posterior uveal melanoma. However, both early and late complications can arise
from these techniques, including vitreous haemorrhage (VH) and retinal detachment
(RD). Choroidal melanomas in Scotland are managed by a single unit, the Scottish
Ocular Oncology Service (SOOS). METHODS: Indications and outcomes from surgery
were analysed for patients undergoing vitrectomy following treatment for uveal
melanoma in the SOOS between 1998 and 2013. RESULTS: Seventeen from 715 cases
(2.4%) required vitrectomy, of which 8/445 (1.8%) followed plaque brachytherapy,
7/43 (16.3%) combined local resection and brachytherapy, and 2/227 (0.9%) PBT.
Case notes were reviewed for 16/17 cases, with surgery indicated for VH in 10
(63%), RD in 5 (31%), and combined VH/RD in 1 (6%). The median interval from
initial tumour treatment to vitrectomy was 5.8 months (range 10 days to 8.8
years). Ten (63%) required early vitrectomy (within 6 months), of which the
majority (70%) followed combined resection/brachytherapy. Six (37%) required late
vitrectomy (after 6 months), of which all were non-clearing VH following plaque
brachytherapy, with proliferative retinopathy in 4/6 (67%), and tumour recurrence
in 2/6 (33%). Overall vision improved in 8 eyes (50%), remained the same in 2
(12.5%), and deteriorated in 6 (37.5%). CONCLUSIONS: Early vitrectomy was most
commonly indicated for RD following local resection, and late vitrectomy for VH
due to radiation retinopathy. The majority of patients undergoing vitrectomy
gained or maintained vision.
PMID- 25853442
TI - Association of histone acetylation at the ACTA2 promoter region with epithelial
mesenchymal transition of lens epithelial cells.
AB - PURPOSE: Epithelial mesenchymal transition (EMT) plays a central role in the
development of fibrotic complications of the lens. The current study is designed
to check whether EMT of lens epithelial cells (LECs) is regulated by epigenetic
modifications and to evaluate the effect of Trichostatin-A (TSA) on the
transforming growth factor-beta (TGF-beta)-induced EMT. METHODS: Fetal human LECs
(FHL124) were treated with TGF-beta2 in the presence or absence of TSA. Levels of
mRNA, protein, as well as localization of alpha-smooth muscle actin (alphaSMA)
were studied along with migration of LECs. Acetylation of histone H4 was analyzed
and chromatin immunoprecipitation (ChIP) was carried out to study the level of
acetylated histone H4 at the promoter of alphaSMA gene (ACTA2). Student's t-test
was used for statistical analysis. RESULTS: TGF-beta2 treatment resulted in
myofibroblast-like changes and increased migratory capacity of FHL124. Protein
and mRNA expression of alphaSMA increased, and immunofluorescence revealed
presence of extensive stress fibers. TSA treatment preserved epithelial
morphology, retarded cell migration, and abrogated an increase in alphaSMA
levels. TSA led to the accumulation of acetylated histone H4 that was reduced on
TGF-beta2 treatment. However, increased level of histone H4 acetylation was found
at the ACTA2 promoter region during TGF-beta treatment. CONCLUSIONS: The
increased level of alphaSMA, a hallmark of EMT in LECs, is associated with
increased level of histone H4 acetylation at its promoter region, and TSA helps
in suppressing EMT by epigenetically reducing this level. TSA thus shows
promising potential in management of fibrotic conditions of the lens.
PMID- 25853444
TI - Apolipoprotein B: novel indicator of elevated intraocular pressure.
AB - PURPOSE: Many studies have reported associations between elevated intraocular
pressure (IOP) and systemic health parameters, which suggest a common mechanism
links IOP elevation and various related cardiometabolic risk factors.
Furthermore, according to a recent study, serum apolipoprotein B (APO B) level is
a predictor of coronary artery disease. This study was undertaken to analyse the
relationship between serum apolipoprotein levels and IOP. METHODS: Healthy people
(28,852) who attended a community hospital for a health checkup between January
2011 and December 2013 were enroled in the study. We measured age, body mass
index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum
levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein
cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and
apolipoprotein A1 (APO A1) and APO B, APO B/APO A1 ratios, and IOP. RESULTS:
Univariate regression analysis showed IOP was positively correlated with BMI,
SBP, DBP, TC, LDL-C, TG, APO B, and APO B/APO A1 (P<0.001), and negatively
correlated with HDL-C (P<0.001). On the other hand, multivariate regression
analysis adjusted for age, BMI, SBP, and DBP, revealed IOP was positive
correlated with TC, TG, LDL-C, APO B, and APO B/APO A1, and negatively correlated
with HDL-C (all <0.05). CONCLUSIONS: Among the various lipid profiles
investigated, APO B was found to be most strongly correlated with IOP, regardless
of sex. Additional studies are required to confirm the validity of apolipoprotein
level as an index for predicting IOP.
PMID- 25853445
TI - The usefulness of the Retinomax autorefractor for childhood screening validated
against a Danish preterm cohort examined at the age of 4 years.
AB - BACKGROUND AND PURPOSE: Refractometers have gained a foothold in childhood
screening for ophthalmic disorders. Given the results of an ophthalmic follow-up
of an extremely preterm Danish cohort, the results of the Retinomax autorefractor
were further evaluated. MATERIALS AND METHODS: A nationwide cohort of infants
born before gestational age 28 weeks (n=178) and 56 term controls were examined
at the age of 4 years. Refraction was given as the cycloplegic Retinomax value.
For this study, we analysed the equipment's confidence value on the printout and
equipment-induced myopization (as the difference between refraction measured
before and after topical cyclopentholate 1%), both items hypothetical with a view
to having identified factual ophthalmic deviations. RESULTS: Thirty-two of 42
eyes with visual acuity <=0.4 had high Retinomax confidence values (8-9); the
Retinomax values were also high in 10 of 12 children with strabismus and lack of
stereopsis. Low values (1-6) were recorded in 11 single eyes, 5 of which were
normal (false positives). Three children already known to have low vision were
unable to cooperate. The overall mean value for equipment-induced myopization was
1.9 D (range, 0-6.87 D). Myopization showed no correlation with visual acuity and
corneal curvature, and a weak positive correlation with refractive value
disappeared when the myopic outliers were excluded. CONCLUSIONS: The hand-held
Retinomax seemed to be reliable for assessing refraction in 4-year-old children,
provided a cycloplegic agent is applied; if used alone, the Retinomax would have
missed several cases of ophthalmic deviation during screening. Equipment-induced
myopization was not indicative.
PMID- 25853446
TI - Corneal collagen crosslinking for keratoconus or corneal ectasia without
epithelial debridement.
AB - PURPOSE: Corneal collagen crosslinking (CXL) is a relatively new technique to
reduce the progression of keratoconus. The technique can be performed with or
without complete debridement of the corneal epithelium. We describe a novel
intermediate technique involving mechanical disruption of the epithelium, and
evaluate its safety and efficacy. METHODS: The case notes of 128 eyes with
progressive keratoconus or iatrogenic corneal ectasia who had undergone CXL using
the epithelial disruption technique were retrospectively reviewed. Thin corneas
were treated with hypotonic riboflavin. All others were treated with an isotonic
solution. Note was made of preoperative and postoperative parameters, including
uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
refraction, endothelial cell count, and corneal tomography. Occurrence of
procedure-related complications was recorded. Statistical analyses were performed
using the paired sample t-test and Wilcoxon signed-rank test, with a level of
P<0.05 being accepted as statistically significant. RESULTS: At 12 months, 41.8%
of patients treated with isotonic riboflavin had improved UCVA and 29.7% had
improved BSCVA. Only 13.4% lost lines of UCVA and 14.9% lost BSCVA. Of the
patients treated with hypotonic riboflavin, at 12 months, 75% demonstrated
stability of BSCVA and 25% had stable Kmax. In addition, 25% showed improved
visual acuity at 12 months, and 58.3% showed regression of their Kmax. Our rate
of short-term complications was comparable to studies using complete epithelial
removal. CONCLUSIONS: CXL with epithelial disruption is a safe and effective
treatment for keratoconus or iatrogenic corneal ectasia, and may be better
tolerated by patients than the epithelium-off technique.
PMID- 25853447
TI - Anatomical and functional recurrence after dexamethasone intravitreal implants: a
6-month prospective study.
AB - PURPOSE: To evaluate the efficacy, safety, and delay of anatomical and functional
recurrence after a first intravitreal injection of dexamethasone implant in eyes
with cystoid macular edema (CME) secondary to retinal vein occlusion (RVO).
METHODS: A 6-month prospective, monocentric and noncomparative case-series of 26
eyes of 26 patients. Best-corrected visual acuity (BCVA) and central subfield
thickness (CST) were measured at baseline and each visit at 1 week, and months 1,
2, 3, 4, 5, and 6 after a first treatment. Primary efficacy outcome was the
proportion of eyes with a minimum three-line improvement from baseline BCVA at
each visit and at 6 months. We also defined different patterns of recurrence:
qualitative anatomical recurrence, quantitative anatomical recurrence and
functional recurrence. A P-value <5% was considered statistically significant.
RESULTS: Mean population age was 69.3 years (SD=12.2; range=42-94 years). Mean ME
duration before treatment was ~9.2 months (SD=11.43; range=0.4-40 months). Eighty
eight percent of eyes achieved a three-line improvement from baseline at 2 months
(P=0.02). The mean delay from baseline until qualitative anatomical, functional,
or quantitative anatomical recurrence was 4.11 months (+/-0.86), 4.31 months (+/
1.33), and 4.40 months (+/-1.14), respectively. Qualitative anatomical recurrence
occurred on average 14.4 days (SD=42.18) before a minimum of one-line BCVA
impairment (functional recurrence). CONCLUSION: Dexamethasone intravitreal
treatment seems to be effective for ME after RVO even with long-duration ME or
poor visual acuity before treatment. Other longer studies should assess the delay
of recurrence after second and further treatments with DEX implants or combined
therapies for ME after RVO.
PMID- 25853448
TI - Ameliorative Effect of Adjunct Therapy of Metformin with Atorvastatin on
Streptozotocin-induced Diabetes Mellitus in Rats.
AB - Metformin has been used for the treatment of diabetes, whereas atorvastatin
reduces the incidence of atherosclerosis and ischemic heart disease. Therefore,
combined treatment with meformin plus atorvastatin may be beneficial in diabetic
patients associated with cardiac disease. The present study was designed to
evaluate the combination therapy of metformin and atorvastatin on streptozotocin
induced diabetes mellitus in rats. Blood pressure, serum insulin, glucose, lipid
profiles and antioxidant enzymes in pancreatic tissues were measured.
Histopathological examination of pancreatic tissues was performed. Streptozotocin
treated rats showed significant decrease in body weight and body mass index.
Streptozotocin-treated rats showed a significant increase in the levels of blood
pressure, serum glucose, triglycerides, total cholesterol and thiobarbituric acid
reactive substance as well as a significant decrease in the levels of serum
insulin, high density lipoprotein and reduced glutathione in pancreatic tissues.
Administration of metformin plus atorvastatin for a period of 14 days
significantly improved these biochemical parameters near to normal. The
protective effect of metformin plus atorvaststin against streptozotocin-induced
diabetes was further confirmed by histopathological examination. The results of
present study suggest that metformin plus atorvastatin possess antioxidant
activity and has a significant protective effect against streptozotocin-induced
diabetes mellitus.
PMID- 25853449
TI - Chinese version of the Aging Perceptions Questionnaire (C-APQ): assessment of
reliability and validity.
AB - OBJECTIVES: To assess the reliability and validity of the Chinese version of
Aging Perceptions Questionnaire (C-APQ). METHOD: Participants aged 65 years and
over were recruited from February 2012 to November 2012. The Aging Perceptions
Questionnaire was translated into Chinese version professionally. Content
validity was examined by a panel of seven experts; item reliabilities were
assessed by test-retest; internal consistency was assessed by Cronbach's alpha
coefficient; half of the sample (N = 379) was selected to explore factorial
structure of the C-APQ by exploratory factor analysis (EFA) and another half of
the sample (N = 379) was selected to confirm the findings from the EFA by
confirmatory factor analysis (CFA). Statistical package SPSS version 18.0 and
Amos 17.0 were used for the analysis. RESULTS: The Cronbach's alpha coefficient
of the C-APQ was 0.884. The test-retest reliability was satisfactory, with all
intraclass correlation coefficients greater than 0.4. The overall content
validity index was greater than 0.99. Seven factors (timeline acute/chronic,
timeline cyclical, emotional representations, control positive, control negative,
consequences positive and consequences negative) were identified in EFA and
confirmed in CFA. CONCLUSION: The C-APQ could be a reliable and a valid measure
of the self-perceptions of aging in the elderly in China, which may help to
improve the life quality and extend longevity of the elderly.
PMID- 25853450
TI - Effects of morphine and midazolam on pharyngeal function, airway protection, and
coordination of breathing and swallowing in healthy adults.
AB - BACKGROUND: Drugs used for sedation in anesthesia and intensive care may cause
pharyngeal dysfunction and increased risk for aspiration. In this study, the
authors investigate the impact of sedative doses of morphine and midazolam on
pharyngeal function during swallowing and coordination of breathing and
swallowing. METHODS: Pharyngeal function, coordination of breathing and
swallowing, and level of sedation were assessed by manometry, videoradiography,
measurements of respiratory airflow, and a visual analog scale in 32 healthy
volunteers (age 19 to 35 yr). After baseline recordings, morphine (0.1 mg/kg) or
midazolam (0.05 mg/kg) was administered intravenously for 20 min, followed by
recordings at 10 and 30 min after the end of infusion. RESULTS: Pharyngeal
dysfunction, seen as misdirected or incomplete swallowing or penetration of bolus
to the airway, increased after morphine infusion to 42 and 44% of swallows
compared with 17% in baseline recordings. Midazolam markedly increased incidence
of pharyngeal dysfunction from 16 to 48% and 59%. Morphine prolonged apnea before
swallowing, and midazolam increased the number of swallows followed by
inspiration. CONCLUSION: Morphine and midazolam in dosages that produce sedation
are associated with increased incidence of pharyngeal dysfunction and
discoordinated breathing and swallowing, a combination impairing airway
protection and potentially increasing the risk for pulmonary aspirations.
PMID- 25853451
TI - What would a proper explanation of anesthesia look like?
PMID- 25853454
TI - Everyone's got it ... it must be familial.
PMID- 25853455
TI - A quick review of the cutaneous findings of the deadly scourge Ebola virus.
PMID- 25853456
TI - Frostbite and chilblains in Upton Sinclair's The Jungle.
PMID- 25853457
TI - Scurvy: curse and cure in new France.
PMID- 25853459
TI - Electron-Withdrawing beta-Substituent, Ring-Strain, and Ortho Effects on
Reactivity, Selectivity, and Stability of o-Alkoxybenzyl Carbocations.
AB - o-Alkoxybenzyl carbocations 1 and 2 were generated by laser flash photolysis of
the corresponding o-alkoxybenzyl alcohols 3 and 4 to understand how the electron
withdrawing beta-substituent, the ring-strain, and the ortho effects affect the
reactivity (electrophilicity), selectivity, and stability of 1 and 2, and to fit
the electrophilicity of 1 and 2 into the current carbocation electrophilicity
scale (E). Our finding is that both the electron-withdrawing beta-substituent and
the ring-strain effects make 1 less stable than 2 by 3.0 kcal/mol. These effects
plus the ortho effect of 2 make 1 more reactive than 2, but the selectivity of 1
and 2 toward amine nucleophiles is almost the same within experimental errors.
The electrophilicity of 1 and 2 has been fit into the current carbocation
electrophilicity scale (E) quite well.
PMID- 25853460
TI - Mandatory Naptimes in Child Care and Children's Nighttime Sleep.
AB - OBJECTIVES: To examine the relationship between mandatory naptimes in child care
and children's nighttime sleep duration, both concurrently and 12 months later
once in school. METHODS: A sample of 168 children (50-72 months; 55% males)
attending licensed child care centers were observed across their morning and
throughout their scheduled naptime. Mandatory naptime was determined as the
period in which children were not permitted any alternative activity except lying
on their bed. Teachers reported each child's napping in child care. Nighttime and
total sleep duration was reported by parents at 2 time points, in child care and
in the second semester of their first school year. General linear models were
used to examine group differences in sleep duration between children experiencing
0 to 60 minutes and >60 minutes of mandatory naptime, adjusting for key
confounders. Path analysis was conducted to test a mediation model in which
mandatory naptime is associated with nighttime sleep duration through increased
napping in child care. RESULTS: Children who experienced >60 minutes of mandatory
naptime in child care had significantly less nighttime sleep than those with 0 to
60 minutes of mandatory naptime. This difference persisted at 12-month follow-up,
once children were in school. Napping in child care mediated the relationship
between mandatory naptime and duration of nighttime sleep. CONCLUSIONS: Exposure
to mandatory naptimes of >60 minutes in child care is associated with decreased
duration of nighttime sleep that endures beyond child care attendance. Given the
large number of children who attend child care, sleep practices within these
settings present an important focus for child health.
PMID- 25853461
TI - Implementing quality by design for biotech products: Are regulators on track?
AB - Quality by design (QbD) is an innovative approach to drug development that has
started to be implemented into the regulatory framework, but currently mainly for
chemical drugs. The recent marketing authorization of the first monoclonal
antibody developed using extensive QbD concepts in the European Union paves the
way for future further regulatory approvals of complex products employing this
cutting-edge technological concept. In this paper, we report and comment on
insights and lessons learnt from the non-public discussions in the European
Medicines Agency's Biologicals Working Party and Committee for Medicinal Products
for Human Use on the key issues during evaluation related to the implementation
of an extensive QbD approach for biotechnology-derived medicinal products.
Sharing these insights could prove useful for future developments in QbD for
biotech products in general and monoclonal antibodies in particular.
PMID- 25853458
TI - A novel mutation P112H in the TARDBP gene associated with frontotemporal lobar
degeneration without motor neuron disease and abundant neuritic amyloid plaques.
AB - INTRODUCTION: Although TDP-43 is the main constituent of the ubiquitinated
cytoplasmic inclusions in the most common forms of frontotemporal lobar
degeneration, TARDBP mutations are not a common cause of familial frontotemporal
dementia, especially in the absence of motor neuron disease. RESULTS: We describe
a pedigree presenting with a complex autosomal dominant disease, with a
heterogeneous clinical phenotype, comprising unspecified dementia, parkinsonism,
frontotemporal dementia and motor neuron disease. Genetic analyses identified a
novel P112H TARDBP double variation located in exon 3 coding for the first RNA
recognition motif of the protein (RRM1). This double mutation is probably
pathogenic based on neuropathological findings, in silico prediction analysis and
exome sequencing. The two autopsied siblings described here presented with
frontotemporal dementia involving multiple cognitive domains and behavior but
lacking symptoms of motor neuron disease throughout the disease course. The
siblings presented with strikingly similar, although atypical, neuropathological
features, including an unclassifiable TDP-43 inclusion pattern, a high burden of
tau-negative beta-amyloid neuritic plaques with an AD-like biochemical profile,
and an unclassifiable 4-repeat tauopathy. The co-occurrence of multiple protein
inclusions points to a pathogenic mechanism that facilitates misfolded protein
interaction and aggregation or a loss of TDP-43 function that somehow impairs
protein clearance. CONCLUSIONS: TARDBP mutation screening should be considered in
familial frontotemporal dementia cases, even without signs or symptoms of motor
neuron disease, especially when other more frequent causes of genetic
frontotemporal dementia (i.e. GRN, C9ORF72, MAPT) have been excluded and when
family history is complex and includes parkinsonism, motor neuron disease and
frontotemporal dementia. Further investigations in this family may provide
insight into the physiological functions of TARDBP.
PMID- 25853462
TI - Efficient microfluidic negative enrichment of circulating tumor cells in blood
using roughened PDMS.
AB - Efficient isolation strategies not based on epithelial biomarker expression are
required to enable non-biased enrichment of circulating tumor cells (CTCs). CTCs
undergoing epithelial-mesenchymal transition (EMT) may be prognostically
relevant, and importantly are not detected with conventional epithelial based
approaches such as CellSearch(r). A method for the non-biased isolation of cancer
cells within a peripheral blood sample utilizing microfluidic mixing PDMS devices
functionalized with anti-CD45 is reported. The introduction of micro and
nanoscale roughness using a single step treatment with sulfuric acid
significantly increases the binding yield of white blood cells (WBCs) to the anti
CD45 conjugated surfaces. Up to 99.99% WBC depletion is achieved with a tumor
cell recovery yield of 50%. This high level of CTC enrichment is expected to
facilitate the detailed characterization of CTCs using for instance, imaging flow
cytometry as demonstrated here.
PMID- 25853463
TI - Raman Characterization of Nanoparticle Transport in Microfluidic Paper-Based
Analytical Devices (MUPADs).
AB - There is great interest in the use of microfluidic paper-based analytical devices
(MUPADs) for low-cost diagnostics. In this contribution, we illustrate the
utility of Raman spectral imaging for both MUPAD characterization and for
quantification of the transport of applied reagents and analytes within these
devices. We evaluated the transport of nanoscale particles within MUPADs using a
suite of differentially functionalized gold (AuNP) and silver (AgNP)
nanoparticles with diameters of 8-64 nm. Nanoparticle transport within the
cellulose matrix was characterized by collection of both Raman and surface
enhanced Raman spectroscopy (SERS) spectral maps that enabled differentiation of
cellulose fibers and characterization of analyte deposition patterns. The
transport of citrate (cit), BSA, PEG, PVP, and DNA functionalized AuNP and AgNP
in wax-printed MUPADs was primarily affected by nanoparticle surface chemistry
rather than particle size or core composition. Sample pH (3-10) influenced the
transport of 15 nm BSA-cit-AuNP, but not 15 nm cit-AuNP, because of the effects
of solution pH on the charge and conformation of BSA. Derjaguin, Landau, Verwey,
and Overbeek theory (DLVO) and extended DLVO (xDLVO) theory are used to explain
the collected experimental results.
PMID- 25853465
TI - A growing interest for intellectual property in universities.
PMID- 25853464
TI - microRNA-155, induced by interleukin-1beta, represses the expression of
microphthalmia-associated transcription factor (MITF-M) in melanoma cells.
AB - Loss of expression of surface antigens represents a significant problem for
cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M)
regulates melanocyte fate by driving expression of many differentiation genes,
whose protein products can be recognized by cytolytic T lymphocytes. We
previously reported that interleukin-1beta (IL-1beta) can downregulate MITF-M
levels. Here we show that downregulation of MITF-M expression by IL-1beta was
paralleled by an upregulation of miR-155 expression in four melanoma lines. We
confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and
demonstrated a role for miR-155 in the IL-1beta-induced repression of MITF-M by
using an antagomiR. Notably, we also observed a strong negative correlation
between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together,
our results indicate that MITF-M downregulation by inflammatory stimuli might be
partly due to miR-155 upregulation. This could represent a novel mechanism of
melanoma immune escape in an inflammatory microenvironment.
PMID- 25853466
TI - Will purple become the new orange? The new FDA purple book for biologics: what
does the future hold?
PMID- 25853468
TI - Transient receptor potential ankyrin 1 (TRPA1) antagonists.
AB - The transient receptor potential ankyrin 1 (TRPA1) channel is an irritant sensor
highly expressed on nociceptive neurons. The clinical use of TRPA1 antagonists is
based on the concept that TRPA1 is active during disease states like neuropathic
pain. Indeed, in Phase 2a proof-of-concept studies the TRPA1 antagonist GRC17536
has shown efficacy in patients with painful diabetic neuropathy. Moreover, animal
studies suggest that the therapeutic value of TRPA1 antagonists extends beyond
pain to pruritus, asthma and cough with limited safety concerns. This review
provides a comprehensive overview of the patent literature (since 2007) on small
molecule inhibitors of the TRPA1 channel. Despite the clear progress, many
unanswered questions remain. Future advancement to Phase 3 studies will assess
the real translational potential of this research field.
PMID- 25853469
TI - Melanocortin-4 receptor modulators for the treatment of obesity: a patent
analysis (2008-2014).
AB - The central melanocortin system and particularly the melanocortin-4 receptor
(MC4R) subtype, plays an important role in the regulation of body weight. The
discovery of orally active MC4R agonists suitable for evaluation in human
clinical trials as weight loss agents has attracted considerable interest over
the past decade, but has proved challenging, in part because of cardiovascular
and behavioral side effects. Currently, the only MC4R agonist in clinical trials
is a peptide identified as RM-493. To avoid some of the undesirable side effects
associated with MC4R activation, new pharmacological approaches for modulating
the MC system have been investigated. In this article, we provide a review of the
MC4R patent landscape from 2008 to 2014 and analyze the physicochemical
properties of compounds described herein.
PMID- 25853470
TI - Click chemistry patents and their impact on drug discovery and chemical biology.
AB - First introduced by K Barry Sharpless in 2001, the term 'click chemistry' soon
became a widely used description of chemical reactions that proceed rapidly,
cleanly and in a manner that is often compatible with aqueous solutions. Click
chemistry is frequently employed throughout the process of drug discovery, and
greatly helps advance research programs in the pharmaceutical industry. It
facilitates library synthesis to support medicinal chemistry optimization, helps
identify the targets and off-targets of drug candidates, and can facilitate the
determination of drug efficacy in clinical trials. In the last decade, a large
number of patent applications covering the various types and utilities of click
chemistry have been filed. In this review, we provide the first analysis of click
chemistry applications.
PMID- 25853471
TI - Corrigendum.
PMID- 25853472
TI - Engelmann spruce site index models: a comparison of model functions and
parameterizations.
AB - Engelmann spruce (Picea engelmannii Parry ex Engelm.) is a high-elevation species
found in western Canada and western USA. As this species becomes increasingly
targeted for harvesting, better height growth information is required for good
management of this species. This project was initiated to fill this need. The
objective of the project was threefold: develop a site index model for Engelmann
spruce; compare the fits and modelling and application issues between three model
formulations and four parameterizations; and more closely examine the grounded
Generalized Algebraic Difference Approach (g-GADA) model parameterization. The
model fitting data consisted of 84 stem analyzed Engelmann spruce site trees
sampled across the Engelmann Spruce - Subalpine Fir biogeoclimatic zone. The
fitted models were based on the Chapman-Richards function, a modified Hossfeld IV
function, and the Schumacher function. The model parameterizations that were
tested are indicator variables, mixed-effects, GADA, and g-GADA. Model evaluation
was based on the finite-sample corrected version of Akaike's Information Criteria
and the estimated variance. Model parameterization had more of an influence on
the fit than did model formulation, with the indicator variable method providing
the best fit, followed by the mixed-effects modelling (9% increase in the
variance for the Chapman-Richards and Schumacher formulations over the indicator
variable parameterization), g-GADA (optimal approach) (335% increase in the
variance), and the GADA/g-GADA (with the GADA parameterization) (346% increase in
the variance). Factors related to the application of the model must be considered
when selecting the model for use as the best fitting methods have the most
barriers in their application in terms of data and software requirements.
PMID- 25853473
TI - Early intervention in thyroidectomy scars: demographics, symptoms, and
prevention.
AB - OBJECTIVE: Although hypertrophic scars are cosmetically problematic for patients
following thyroidectomy, the associated risk factors are not well defined. Our
objective was to determine the factors associated with hypertrophic scar
development following thyroidectomy. METHOD: A retrospective chart review was
performed collecting data on sex, age, body mass index (BMI), operation site,
skin characteristics (pigmentation, erythema, elasticity, and hydration), and
clinical scar characteristics (itching, tightening, induration, adhesion, and
oedema). It was also noted if the patient had early scar intervention with
intralesional steroid injection or non-ablative fractional laser irradiation, and
preventive topical treatment agents. The effects of these factors were analysed
using univariate and multivariate analyses. RESULTS: Data from 1141 patients
showed the incidence of hypertrophic scars was 13.9%. Significant variables in
univariate analysis were combined for multivariate analysis. Young age, high BMI,
itching, tightening, induration, and adhesion were associated with hypertrophic
scar formation. Early scar intervention, as well as the use of preventive topical
agents, were associated with decreased hypertrophic scar formation. CONCLUSION:
Based on our results, we suggest that dermatologists consider using non-ablative
fractional laser, intralesional steroid injection, and topical preventive agents
to lower the incidence of hypertrophic scars, especially in young patients or
those with high BMI and/or clinical symptoms such as itching, tightening,
induration, and adhesion.
PMID- 25853474
TI - Use of an autologous leucocyte and platelet-rich fibrin patch on hard-to-heal
DFUs: a pilot study.
AB - OBJECTIVE: Leucopatch is a leukocyte and platelet-rich fibrin patch that provides
concentrated blood cells and signal substances to the surface of an ulcer. It is
produced by centrifugation of the patient's own venous blood. The aim of this
pilot multicentre cohort study was to evaluate effects of the leucocyte patch in
patients with hard-to-heal diabetic foot ulcers (DFUs). METHOD: Non-ischaemic
Wagner grade 1 or 2 DFUs with a duration of more than 6 weeks and a maximal area
of 10cm2 were included. Patients with >40% ulcer area change during a two-week
run-in period were excluded. The treatment was applied once a week for up to 19
treatments or until the foot ulcer was completely epithelialised. The primary
endpoint was healing within 20 weeks. RESULTS: Of the 60 patients who gave
consent 16 were excluded during run-in period, 44 patients initiated study
treatment and 39 were included in the per-protocol analysis. Complete
epithelisation was achieved in 34% (per-protocol analysis 36%) at 12 weeks and
52% (59%) at 20 weeks. In patients with ulcer duration less than 6 months, 73% of
ulcers healed within 20 weeks. Patients with healed ulcers had larger ulcer area
reduction during the first two treatment weeks compared to non-healers. Adverse
events were mild and rare. CONCLUSION: The leucocyte patch is well-tolerated,
easy to use and has potential in the armamentarium of the DFU treatment, provided
this outcome is confirmed in an appropriately powered randomised clinical trial.
PMID- 25853475
TI - The prevention and management of pressure ulcers: summary of updated NICE
guidance.
PMID- 25853476
TI - Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona
virus.
AB - The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus,
and Cuevavirus. Some members of the EBOV genus, including Zaire ebolavirus
(ZEBOV), can cause lethal haemorrhagic fever in humans. During 2014 an
unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing,
resulting in over 10,000 deaths, and causing global concern of uncontrolled
disease. To meet this challenge a rapid-acting vaccine is needed. Many vaccine
approaches have shown promise in being able to protect nonhuman primates against
ZEBOV. In response to the current ZEBOV outbreak several of these vaccines have
been fast tracked for human use. However, it is not known whether any of these
vaccines can provide protection against the new outbreak Makona strain of ZEBOV.
One of these approaches is a first-generation recombinant vesicular stomatitis
virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV).
To address safety concerns associated with this vector, we developed two
candidate, further-attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines
produced an approximately tenfold lower vaccine-associated viraemia compared to
the first-generation vaccine and both provided complete, single-dose protection
of macaques from lethal challenge with the Makona outbreak strain of ZEBOV.
PMID- 25853477
TI - A smart tumor targeting peptide-drug conjugate, pHLIP-SS-DOX: synthesis and
cellular uptake on MCF-7 and MCF-7/Adr cells.
AB - Doxorubicin (DOX) is a potent anticancer drug for the treatment of tumors, but
the poor specificity and multi-drug resistance (MDR) on tumor cells have
restricted its application. Here, a pH and reduction-responsive peptide-drug
conjugate (PDC), pHLIP-SS-DOX, was synthesized to overcome these drawbacks. pH
low insertion peptide (pHLIP) is a cell penetrating peptide (CPP) with pH
dependent transmembrane ability. And because of the unique cell membrane
insertion pattern, it might reverse the MDR. The cellular uptake study showed
that on both drug-sensitive MCF-7 and drug-resistant MCF-7/Adr cells, pHLIP-SS
DOX obviously facilitated the uptake of DOX at pH 6.0 and the uptake level on MCF
7/Adr cells was similar with that on MCF-7 cells, indicating that pHLIP-SS-DOX
had the ability to target acidic tumor cells and reverse MDR. In vitro
cytotoxicity study mediated by GSH-OEt demonstrated that the cytotoxic effect of
pHLIP-SS-DOX was reduction responsive, with obvious cytotoxicity at pH 6.0; while
it had poor cytotoxicity at pH 7.4, no matter with or without GSH-OEt
pretreatment. This illustrated that pHLIP could deliver DOX into tumor cells with
acidic microenvironment specifically and could not deliver drugs into normal
cells with neutral microenvironment. In summary, pHLIP-SS-DOX is a promising
strategy to target drugs to tumors and provides a possibility to overcome MDR.
PMID- 25853478
TI - Development and in vitro/in vivo evaluation of Zn-pectinate microparticles
reinforced with chitosan for the colonic delivery of progesterone.
AB - The colon is a promising target for drug delivery owing to its long transit time
of up to 78 h, which is likely to increase the time available for drug
absorption. Progesterone has a short elimination half-life and undergoes
extensive first-pass metabolism, which results in very low oral bioavailability
(~25%). To overcome these shortcomings, we developed an oral multiparticulate
system for the colonic delivery of progesterone. Zn-pectinate/chitosan
microparticles were prepared by ionotropic gelation and characterized for their
size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling
behavior. The effect of cross-linking pH, cross-linking time and chitosan
concentration on progesterone release were also studied. Spherical microparticles
having a diameter of 580-720 um were obtained. Drug entrapment efficiency of ~75
100% was obtained depending on the microparticle composition. Microparticle
mucoadhesive properties were dependent on the pectin concentration, as well as
the cross-linking pH. Progesterone release in simulated gastric fluids was
minimal (3-9%), followed by burst release at pH 6.8 and a sustained phase at pH
7.4. The in vivo study revealed that the microparticles significantly increased
progesterone residence time in the plasma and increased its relative
bioavailability to ~168%, compared to the drug alone. This study confirms the
potential of Zn-pectinate/chitosan microparticles as a colon-specific drug
delivery system able to enhance the oral bioavailability of progesterone or
similar drugs.
PMID- 25853479
TI - Pharmacokinetics and tissue distribution study in mice of triptolide-loaded lipid
emulsion and accumulation effect on pancreas.
AB - Triptolide (TP) shows strong anti-tumor activities on various cancer cells,
especially on pancreatic cancer. TP inhibits HSP70 expression leading to cell
death in pancreatic cancer cells and induces cell death by apoptotic and
autophagic pathways. In order to increase the therapeutic index of TP, a novel
intravenous TP-loaded delivery system, TP-loaded lipid emulsion (TP-LE), has been
developed to treat solid tumor. In the present study, the preparation and
characterization of TP-LE were described. The pharmacokinetics and tissue
distribution study of TP-LE in mice were also evaluated. Results demonstrated
that TP-LE had an average particle size of 154.6 nm, entrapment efficiency (EE%)
of 87%, zeta potential of -0.903 mV and autoclaved stability. The pharmacokinetic
study showed that blood concentrations of both TP-LE and TP reached a maximum at
the end of intravenous administration (1.25 mg/kg) and declined rapidly within
the first 10 min with a mean residence time (MRT) of about 10 min. In the tissue
distribution study, a preferential accumulation and longer residence time of drug
in pancreas were found in TP-LE. The AUC0-60min of TP-LE in pancreas was 2.19
times in comparison to free TP, suggesting that the use of TP-LE conferred
improvements in biodistribution, accumulation and therapeutic efficacy in
pancreas. Moreover, the concentrations of TP-LE in heart, lung and kidney were
lower than that of the TP group, indicating the potential for reduced toxicity of
TP-LE. Together, all the results show that TP-LE appears to be a promising
formulation for using TP in treating cancer, and more specifically pancreatic
cancer.
PMID- 25853480
TI - Preparation of sodium cholate-based micelles through non-covalent ibonding
interaction and application as oral delivery systems for paclitaxel.
AB - In present study, two types of micelles based on sodium cholate (NaC) were
prepared through non-covalent bonding interaction and the potential of micelles
as oral drug delivery systems for paclitaxel (PTX) was evaluated. Pluronic
chitosan (F127-CS) and Pluronic-poly (acrylic acid) (F127-PAA) copolymers were
synthesized. Electrostatic interaction and hydrogen bond were used to prepare
F127-CS/NaC micelles and F127-PAA/NaC micelles, respectively. The physicochemical
characteristics of micelles were determined. An average diameter of 67.5 nm and
unimodal pattern of size distribution were observed for F127-CS/NaC micelles.
While for F127-PAA/NaC micelles, an average diameter of 85.89 nm and non-unimodal
pattern of size distribution were observed. The results revealed that F127-CS/NaC
micelles were more integrated than F127-PAA/NaC micelles. Further experiments
showed that the F127-CS/NaC micelles had a higher drug-loading content of 12.8%
and a lower critical micelle concentration (CMC) of 2.5 * 10-3 mol/L compared
with F127-PAA/NaC micelles. In vitro cytotoxicity analysis demonstrated that the
PTX-loaded F127-CS/NaC micelles were of great efficiency in inhibiting the growth
of drug-resistant breast cancer MCF-7 cells (MCF-7/Adr). The intragastric
administration of the PTX-loaded F127-CS/NaC micelles in rats provided a 4.33
fold higher absolute bioavailability compared to commercial Taxol(r), indicating
an efficient oral absorption of PTX delivered by micelles. These findings signify
that F127-CS/NaC micelle may be a promising carrier for the delivery of PTX.
PMID- 25853481
TI - Use of Amniotic Microparticles Coated With Fibroblasts Overexpressing SDF-1alpha
to Create an Environment Conducive to Neovascularization for Repair of Full
Thickness Skin Defects.
AB - As angiogenesis and vasculogenesis involve the complex network structures of
various types of cells, extracellular matrix components, and cytokines, it is
still difficult to exactly mimic the microenvironment of vascularization in vivo.
In our study, we constructed a complex containing highly proliferative
fibroblasts that can secrete extracellular matrix components and growth factors
to chemotaxize endothelial progenitor cells (EPCs) in an attempt to create an
ideal microenvironment for quick vascularization. Amniotic membrane
microparticles (mAM) rich in type IV collagen (COL IV) and laminin (LN) were
prepared, and human dermal fibroblasts (HDF) were infected with lentivirus (LV)
of overexpression of SDF-1alpha to construct SDF-1alpha(ov)HDF. Using the rotary
cell culture system (RCCS), mAM was loaded with HDF or SDF-1alpha(ov)HDF to
construct HDF-mAM and SDF-1alpha(ov)HDF-mAM complexes. The complexes were able to
secrete various types of active peptides (IL-6, IL-8, TGF-beta, and bFGF) during
in vitro culture. In addition, SDF-1alpha(ov)HDF-mAM complex highly expressed SDF
1alpha. Transwell assay showed SDF-1alpha(ov)HDF-mAM complex had an apparent
chemotactic effect on EPCs. Transplantation of complexes onto full-thickness skin
defects of C57BL mice further demonstrated that SDF-1alpha expression and the
number of peripheral EPCs at days 3, 5, and 7 in the SDF-1alpha(ov)HDF-mAM group
were significantly higher than that in other groups (p < 0.01). The local
microvascular density at day 10 of transplantation showed that the microvascular
density in the SDF-1alpha(ov)HDF-mAM group was significantly higher than that in
HDF-mAM group (p < 0.01). In conclusion, HDF-mAM had a strong proliferative
activity and could be used to create a sound microenvironment for quick
vascularization by secreting multiple cytokines and extracellular matrix
components. Overexpression of SDF-1alpha could chemotaxize EPCs to reach local
wounds, thus further accelerating angiogenesis in the transplant site. The
technique described may prove to be a new model for accelerating vascularization
of tissue and organ transplants and chronic ischemic wounds.
PMID- 25853482
TI - A comparison of disease burden in rheumatoid arthritis, psoriatic arthritis and
axial spondyloarthritis.
AB - OBJECTIVE: The main objective of this study was to compare disease burden in
rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis
(ax-SpA). METHODS: In this cross-sectional study, all the RA (1093), PsA (365)
and ax-SpA (333) patients who visited the out-patient clinic of the Hospital of
Southern Norway Trust during the year 2013 were included; the RA patients all had
a RA diagnosis verified by the treating rheumatologist, the PsA patients all
fulfilled the ClASsification for Psoriatic ARthritis (CASPAR) criteria and the ax
SpA patients all fulfilled the Assessment of SpondyloArthritis international
Society (ASAS) classification criteria for ax-SpA. Patient-reported health
status, demographic variables, medications, and composite scores of disease
activity were assessed. The main analyses were performed using General Linear
Models adjusted for age, sex and multiple comparisons. Correlation analyses were
performed using Spearman's rho. RESULTS: The reported pain, joint pain, patient's
global assessment and fatigue were similar in PsA and ax-SpA, but significantly
lower in RA. The 28-joint Disease Activity Score (DAS28) (0.3+/-0.1, p = 0.003),
Clinical Disease Activity Index (CDAI) (1.0+/-0.4, p = 0.028) and Routine
Assessment of Patient Index Data 3 (RAPID3) (0.4+/-0.1, p = 0.004) were all
significantly higher in PsA vs. RA. RAPID3 showed moderate to high correlation
with DAS28 (rho = 0.521, p<0.001) and CDAI (rho = 0.768, p<0.001) in RA and PsA,
and with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (rho =
0.902, p<0.001) and Bath Ankylosing Spondylitis Functional Index (BASFI) (0.865,
p<0.001) in ax-SpA and PsA. CONCLUSION: In conclusion, patient- reported outcome
measures were similar in our population of PsA and ax-SpA patients, but
significantly lower for the RA patients. Composite disease activity measures were
lower in RA than in PsA and ax-SpA, but the magnitude of these differences was
small and probably not of clinical significance. Our study indicates that disease
burden in RA, PsA and ax-SpA may be more similar than previously demonstrated.
PMID- 25853485
TI - Supramolecular polymerization: a coarse grained molecular dynamics study.
AB - A coarse-grained (CG) force field to model the self-assembly of benzene-1,3,5
tricarboxamide (BTA) class of compounds in nonpolar solvents has been developed.
The model includes an intrinsic point dipole embedded on one of the CG beads so
as to impart a macrodipole moment to the oligomer, one of its characteristic
feature. Chemical specificity has been preserved by benchmarking against results,
including dimerization and solvation free energies, obtained from an all-atom
representation. Starting from a well-dispersed configuration in n-nonane, BTA
molecules self-assemble to form one-dimensional stacks. Free energy (FE) changes
for the various manner in which short oligomers can exchange between the
assembled and the dispersed states have been calculated. These calculations show
BTA to self-assemble via a downhill cooperative mechanism with a nucleus size of
three.
PMID- 25853484
TI - A suggested new bacteriophage genus, "Kp34likevirus", within the
Autographivirinae subfamily of Podoviridae.
AB - Klebsiella pneumoniae phages vB_KpnP_SU503 (SU503) and vB_KpnP_SU552A (SU552A)
are virulent viruses belonging to the Autographivirinae subfamily of Podoviridae
that infect and kill multi-resistant K. pneumoniae isolates. Phages SU503 and
SU552A show high pairwise nucleotide identity to Klebsiella phages KP34
(NC_013649), F19 (NC_023567) and NTUH-K2044-K1-1 (NC_025418). Bioinformatic
analysis of these phage genomes show high conservation of gene arrangement and
gene content, conserved catalytically active residues of their RNA polymerase, a
common and specific lysis cassette, and form a joint cluster in phylogenetic
analysis of their conserved genes. Also, we have performed biological
characterization of the burst size, latent period, host specificity (together
with KP34 and NTUH-K2044-K1-1), morphology, and structural genes as well as
sensitivity testing to various conditions. Based on the analyses of these phages,
the creation of a new phage genus is suggested within the Autographivirinae,
called "Kp34likevirus" after their type phage, KP34. This genus should encompass
the recently genome sequenced Klebsiella phages KP34, SU503, SU552A, F19 and NTUH
K2044-K1-1.
PMID- 25853486
TI - Anthocyanin Accumulation and Molecular Analysis of Correlated Genes in Purple
Kohlrabi (Brassica oleracea var. gongylodes L.).
AB - Kohlrabi (Brassica oleracea var. gongylodes L.) is an important dietary vegetable
cultivated and consumed widely for the round swollen stem. Purple kohlrabi shows
abundant anthocyanin accumulation in the leaf and swollen stem. Here, different
kinds of anthocyanins were separated and identified from the purple kohlrabi
cultivar (Kolibri) by high-performance liquid chromatography-electrospray
ionization tandem mass spectrometry. In order to study the molecular mechanism of
anthocyanin biosynthesis in purple kohlrabi, the expression of anthocyanin
biosynthetic genes and regulatory genes in purple kohlrabi and a green cultivar
(Winner) was examined by quantitative PCR. In comparison with the colorless parts
in the two cultivars, most of the anthocyanin biosynthetic genes and two
transcription factors were drastically upregulated in the purple tissues. To
study the effects of light shed on the anthocyanin accumulation of kohlrabi,
total anthocyanin contents and transcripts of associated genes were analyzed in
sprouts of both cultivars grown under light and dark conditions.
PMID- 25853488
TI - Ulcerated Plaque With Lymphocutaneous Spread.
PMID- 25853487
TI - Deep transcriptome sequencing provides new insights into the structural and
functional organization of the wheat genome.
AB - BACKGROUND: Because of its size, allohexaploid nature, and high repeat content,
the bread wheat genome is a good model to study the impact of the genome
structure on gene organization, function, and regulation. However, because of the
lack of a reference genome sequence, such studies have long been hampered and our
knowledge of the wheat gene space is still limited. The access to the reference
sequence of the wheat chromosome 3B provided us with an opportunity to study the
wheat transcriptome and its relationships to genome and gene structure at a level
that has never been reached before. RESULTS: By combining this sequence with RNA
seq data, we construct a fine transcriptome map of the chromosome 3B. More than
8,800 transcription sites are identified, that are distributed throughout the
entire chromosome. Expression level, expression breadth, alternative splicing as
well as several structural features of genes, including transcript length, number
of exons, and cumulative intron length are investigated. Our analysis reveals a
non-monotonic relationship between gene expression and structure and leads to the
hypothesis that gene structure is determined by its function, whereas gene
expression is subject to energetic cost. Moreover, we observe a recombination
based partitioning at the gene structure and function level. CONCLUSIONS: Our
analysis provides new insights into the relationships between gene and genome
structure and function. It reveals mechanisms conserved with other plant species
as well as superimposed evolutionary forces that shaped the wheat gene space,
likely participating in wheat adaptation.
PMID- 25853489
TI - HIV Infection Leads to Redistribution of Leaky Claudin-2 in the Intestine of
Humanized SCID IL-2R(-/-) Hu-PBMC Mice.
PMID- 25853490
TI - A Bayesian model of category-specific emotional brain responses.
AB - Understanding emotion is critical for a science of healthy and disordered brain
function, but the neurophysiological basis of emotional experience is still
poorly understood. We analyzed human brain activity patterns from 148 studies of
emotion categories (2159 total participants) using a novel hierarchical Bayesian
model. The model allowed us to classify which of five categories--fear, anger,
disgust, sadness, or happiness--is engaged by a study with 66% accuracy (43-86%
across categories). Analyses of the activity patterns encoded in the model
revealed that each emotion category is associated with unique, prototypical
patterns of activity across multiple brain systems including the cortex,
thalamus, amygdala, and other structures. The results indicate that emotion
categories are not contained within any one region or system, but are represented
as configurations across multiple brain networks. The model provides a precise
summary of the prototypical patterns for each emotion category, and demonstrates
that a sufficient characterization of emotion categories relies on (a)
differential patterns of involvement in neocortical systems that differ between
humans and other species, and (b) distinctive patterns of cortical-subcortical
interactions. Thus, these findings are incompatible with several contemporary
theories of emotion, including those that emphasize emotion-dedicated brain
systems and those that propose emotion is localized primarily in subcortical
activity. They are consistent with componential and constructionist views, which
propose that emotions are differentiated by a combination of perceptual,
mnemonic, prospective, and motivational elements. Such brain-based models of
emotion provide a foundation for new translational and clinical approaches.
PMID- 25853491
TI - Parasite prevalence corresponds to host life history in a diverse assemblage of
afrotropical birds and haemosporidian parasites.
AB - Avian host life history traits have been hypothesized to predict rates of
infection by haemosporidian parasites. Using molecular techniques, we tested this
hypothesis for parasites from three haemosporidian genera (Plasmodium,
Haemoproteus, and Leucocytozoon) collected from a diverse sampling of birds in
northern Malawi. We found that host life history traits were significantly
associated with parasitism rates by all three parasite genera. Nest type and nest
location predicted infection probability for all three parasite genera, whereas
flocking behavior is an important predictor of Plasmodium and Haemoproteus
infection and habitat is an important predictor of Leucocytozoon infection.
Parasite prevalence was 79.1% across all individuals sampled, higher than that
reported for comparable studies from any other region of the world. Parasite
diversity was also exceptionally high, with 248 parasite cytochrome b lineages
identified from 152 host species. A large proportion of Plasmodium, Haemoproteus,
and Leucocytozoon parasite DNA sequences identified in this study represent new,
previously undocumented lineages (n = 201; 81% of total identified) based on
BLAST queries against the avian malaria database, MalAvi.
PMID- 25853492
TI - Extremely low microsatellite diversity but distinct population structure in a
long-lived threatened species, the Australian lungfish Neoceratodus forsteri
(Dipnoi).
AB - The Australian lungfish is a unique living representative of an ancient dipnoan
lineage, listed as 'vulnerable' to extinction under Australia's Environment
Protection and Biodiversity Conservation Act 1999. Historical accounts indicate
this species occurred naturally in two adjacent river systems in Australia, the
Burnett and Mary. Current day populations in other rivers are thought to have
arisen by translocation from these source populations. Early genetic work
detected very little variation and so had limited power to answer questions
relevant for management including how genetic variation is partitioned within and
among sub-populations. In this study, we use newly developed microsatellite
markers to examine samples from the Burnett and Mary Rivers, as well as from two
populations thought to be of translocated origin, Brisbane and North Pine. We
test whether there is significant genetic structure among and within river
drainages; assign putatively translocated populations to potential source
populations; and estimate effective population sizes. Eleven polymorphic
microsatellite loci genotyped in 218 individuals gave an average within
population heterozygosity of 0.39 which is low relative to other threatened taxa
and for freshwater fishes in general. Based on FST values (average over loci =
0.11) and STRUCTURE analyses, we identify three distinct populations in the
natural range, one in the Burnett and two distinct populations in the Mary. These
analyses also support the hypothesis that the Mary River is the likely source of
translocated populations in the Brisbane and North Pine rivers, which agrees with
historical published records of a translocation event giving rise to these
populations. We were unable to obtain bounded estimates of effective population
size, as we have too few genotype combinations, although point estimates were
low, ranging from 29 - 129. We recommend that, in order to preserve any local
adaptation in the three distinct populations that they be managed separately.
PMID- 25853494
TI - Aflatoxin M1: Prevalence and decontamination strategies in milk and milk
products.
AB - Aflatoxin M1 (AFM1) in milk is among the most carcinogenic compounds, relatively
high levels being consumed, especially by the most vulnerable age groups, i.e.
infants and the elderly. Reports on its prevalence are constantly being received
from various parts of the world compelling nations to establish their own
standard limits for AFM1. Global review of the literature indicates the existence
of methods of partial decontamination of AFM1, however; evidence based studies do
not suggest that any single strategy as a coherent and complete solution to the
issue. Microbial decontamination of AFM1 has emerged as the most suitable method
up to now but the stability of toxin-microbial cell complexes still remains
questionable. This review discusses the chemical nature, established maximum
permissible limits and prevalence of AFM1 in various countries from 2009 to 2014.
Moreover, the possible mechanisms for AFM1 reduction mainly the microbial
decontamination and the stability and bioaccessibility of microbial-AFM1
complexes are also discussed.
PMID- 25853493
TI - Protective role of PGC-1alpha in diabetic nephropathy is associated with the
inhibition of ROS through mitochondrial dynamic remodeling.
AB - The overproduction of mitochondrial reactive oxygen species (ROS) plays a key
role in the pathogenesis of diabetic nephropathy (DN). However, the underlying
molecular mechanism remains unclear. Our aim was to investigate the role of PGC
1alpha in the pathogenesis of DN. Rat glomerular mesangial cells (RMCs) were
incubated in normal or high glucose medium with or without the PGC-1alpha
overexpressing plasmid (pcDNA3-PGC-1alpha) for 48 h. In the diabetic rats,
decreased PGC-1alpha expression was associated with increased mitochondrial ROS
generation in the renal cortex, increased proteinuria, glomerular hypertrophy,
and higher glomerular 8-OHdG (a biomarker for oxidative stress). In vitro,
hyperglycemia induced the downregulation of PGC-1alpha, which led to increased
DRP1 expression, increased mitochondrial fragmentation and damaged network
structure. This was associated with an increase in ROS generation and mesangial
cell hypertrophy. These pathological changes were reversed in vitro by the
transfection of pcDNA3-PGC-1alpha. These data suggest that PGC-1alpha may protect
DN via the inhibition of DRP1-mediated mitochondrial dynamic remodeling and ROS
production. These findings may assist the development of novel therapeutic
strategies for patients with DN.
PMID- 25853495
TI - Pathogenic microbes manipulate cofilin activity to subvert actin cytoskeleton.
AB - Actin-depolymerizing factor (ADF)/cofilin proteins are key players in controlling
the temporal and spatial extent of actin dynamics, which is crucial for mediating
host-pathogen interactions. Pathogenic microbes have evolved molecular mechanisms
to manipulate cofilin activity to subvert the actin cytoskeletal system in host
cells, promoting their internalization into the target cells, modifying the
replication niche and facilitating their intracellular and intercellular
dissemination. The study of how these pathogens exploit cofilin pathways is
crucial for understanding infectious disease and providing potential targets for
drug therapies.
PMID- 25853483
TI - The evolution of poxvirus vaccines.
AB - After Edward Jenner established human vaccination over 200 years ago, attenuated
poxviruses became key players to contain the deadliest virus of its own family:
Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and
horsepox virus (HSPV) were extensively used to this end, passaged in cattle and
humans until the appearance of vaccinia virus (VACV), which was used in the final
campaigns aimed to eradicate the disease, an endeavor that was accomplished by
the World Health Organization (WHO) in 1980. Ever since, naturally evolved
strains used for vaccination were introduced into research laboratories where
VACV and other poxviruses with improved safety profiles were generated.
Recombinant DNA technology along with the DNA genome features of this virus
family allowed the generation of vaccines against heterologous diseases, and the
specific insertion and deletion of poxvirus genes generated an even broader
spectrum of modified viruses with new properties that increase their
immunogenicity and safety profile as vaccine vectors. In this review, we
highlight the evolution of poxvirus vaccines, from first generation to the
current status, pointing out how different vaccines have emerged and approaches
that are being followed up in the development of more rational vaccines against a
wide range of diseases.
PMID- 25853496
TI - A new method of detecting pulmonary nodules with PET/CT based on an improved
watershed algorithm.
AB - BACKGROUND: Integrated 18F-fluorodeoxyglucose positron emission
tomography/computed tomography (18F-FDG PET/CT) is widely performed for staging
solitary pulmonary nodules (SPNs). However, the diagnostic efficacy of SPNs based
on PET/CT is not optimal. Here, we propose a method of detection based on PET/CT
that can differentiate malignant and benign SPNs with few false-positives.
METHOD: Our proposed method combines the features of positron-emission tomography
(PET) and computed tomography (CT). A dynamic threshold segmentation method was
used to identify lung parenchyma in CT images and suspicious areas in PET images.
Then, an improved watershed method was used to mark suspicious areas on the CT
image. Next, the support vector machine (SVM) method was used to classify SPNs
based on textural features of CT images and metabolic features of PET images to
validate the proposed method. RESULTS: Our proposed method was more efficient
than traditional methods and methods based on the CT or PET features alone
(sensitivity 95.6%; average of 2.9 false positives per scan).
PMID- 25853497
TI - Genital herpes: oral antiviral treatments.
AB - INTRODUCTION: Genital herpes is an infection with herpes simplex virus type 1
(HSV-1) or type 2 (HSV-2), and is among the most common sexually transmitted
diseases. METHODS AND OUTCOMES: We conducted a systematic review and aimed to
answer the following clinical questions: What are the effects of different oral
antiviral treatments versus each other for a first episode of genital herpes in
HIV-negative people? What are the effects of different antiviral treatments for
genital herpes in HIV-positive people? We searched: Medline, Embase, The Cochrane
Library, and other important databases up to October 2013 (Clinical Evidence
reviews are updated periodically; please check our website for the most up-to
date version of this review). We included harms alerts from relevant
organisations such as the US Food and Drug Administration (FDA) and the UK
Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
eight studies that met our inclusion criteria. We performed a GRADE evaluation of
the quality of evidence for interventions. CONCLUSIONS: In this systematic review
we present information relating to the effectiveness and safety of the following
interventions: aciclovir, famciclovir, and valaciclovir.
PMID- 25853499
TI - Rapid and simple preparation of remarkably stable binary nanoparticle planet
satellite assemblies.
AB - We demonstrate a straightforward nonbiomolecular approach for self-assembly of
binary NP planet-satellite superstructures, which display remarkable colloidal
and structural stability under variations in temperature, pH, ionic strength and
solvent. The readily scalable process produces highly homogeneous samples and is
tolerant to variations in building block size and shape, giving rapid access to a
structurally diverse range of robust binary NP assemblies.
PMID- 25853498
TI - A PHF8 homolog in C. elegans promotes DNA repair via homologous recombination.
AB - PHF8 is a JmjC domain-containing histone demethylase, defects in which are
associated with X-linked mental retardation. In this study, we examined the roles
of two PHF8 homologs, JMJD-1.1 and JMJD-1.2, in the model organism C. elegans in
response to DNA damage. A deletion mutation in either of the genes led to
hypersensitivity to interstrand DNA crosslinks (ICLs), while only mutation of
jmjd-1.1 resulted in hypersensitivity to double-strand DNA breaks (DSBs). In
response to ICLs, JMJD-1.1 did not affect the focus formation of FCD-2, a homolog
of FANCD2, a key protein in the Fanconi anemia pathway. However, the dynamic
behavior of RPA-1 and RAD-51 was affected by the mutation: the accumulations of
both proteins at ICLs appeared normal, but their subsequent disappearance was
retarded, suggesting that later steps of homologous recombination were defective.
Similar changes in the dynamic behavior of RPA-1 and RAD-51 were seen in response
to DSBs, supporting a role of JMJD-1.1 in homologous recombination. Such a role
was also supported by our finding that the hypersensitivity of jmjd-1.1 worms to
ICLs was rescued by knockdown of lig-4, a homolog of Ligase 4 active in
nonhomologous end-joining. The hypersensitivity of jmjd-1.1 worms to ICLs was
increased by rad-54 knockdown, suggesting that JMJD-1.1 acts in parallel with RAD
54 in modulating chromatin structure. Indeed, the level of histone H3 Lys9 tri
methylation, a marker of heterochromatin, was higher in jmjd-1.1 cells than in
wild-type cells. We conclude that the histone demethylase JMJD-1.1 influences
homologous recombination either by relaxing heterochromatin structure or by
indirectly regulating the expression of multiple genes affecting DNA repair.
PMID- 25853500
TI - A New Mechanism in Electrochemical Process for Arsenic Oxidation: Production of
H2O2 from Anodic O2 Reduction on the Cathode under Automatically Developed
Alkaline Conditions.
AB - Electrochemical cathodes are often used to reduce contaminants or produce
oxidizing substances (i.e., H2O2). Alkaline conditions develop automatically
around the cathode in electrochemical processes, and O2 diffuses onto the cathode
easily. However, limited attention is paid to contaminant transformation by the
reactive species produced on the cathode under oxic and alkaline conditions due
to the inapplicability of pH for Fenton reaction. In this study, a new oxidation
mechanism on the cathode is presented for contaminant transformation under
automatically developed alkaline conditions. In an electrochemical sand column,
6.67 MUM As(III) was oxidized by 36% when it passed through the cathode under the
conditions of 30 mA current, an initial pH of 7.5 and a flow rate of 2 mL/min.
Under the alkaline conditions (pH 10.0-11.0) that developed automatically around
the cathode, the reduction potential of As(III) decreased greatly, allowing a
pronounced oxidation by the small quantities of H2O2 produced from O2 reduction
on the cathode. As(III) oxidation was further increased by the presence of soil
pore water and groundwater solutes of HCO3-, Ca2+, Mg2+ and humic acid. The new
oxidation mechanism found for the cathode under localized alkaline conditions
supplements the fundamentals of contaminant transformation in electrochemical
processes.
PMID- 25853501
TI - A Ferric-Peroxo Intermediate in the Oxidation of Heme by IsdI.
AB - The canonical heme oxygenases (HOs) catalyze heme oxidation via a heme-bound
hydroperoxo intermediate that is stabilized by a water cluster at the active site
of the enzyme. In contrast, the hydrophobic active site of IsdI, a heme-degrading
enzyme from Staphylococcus aureus, lacks a water cluster and is expected to
oxidize heme by an alternative mechanism. Reaction of the IsdI-heme complex with
either H2O2 or m-chloroperoxybenzoic acid fails to produce a specific oxidized
heme iron intermediate, suggesting that ferric-hydroperoxo or ferryl derivatives
of IsdI are not involved in the catalytic mechanism of this enzyme. IsdI lacks a
proton-donating group in the distal heme pocket, so the possible involvement of a
ferric-peroxo intermediate has been evaluated. Density functional theory (DFT)
calculations indicate that heme oxidation involving a ferric-peroxo intermediate
is energetically accessible, whereas the energy barrier for a reaction involving
a ferric-hydroperoxo intermediate is too great in the absence of a proton donor.
We propose that IsdI catalyzes heme oxidation through nucleophilic attack by the
heme-bound peroxo species. This proposal is consistent with our previous
demonstration by nuclear magnetic resonance spectroscopy that heme ruffling
increases the susceptibility of the meso-carbon of heme to nucleophilic attack.
PMID- 25853503
TI - Orbital Mucormycosis Following Periorbital Cutaneous Infection.
AB - Mucormycosis is an aggressive fungal infection characterized by rapidly
progressive angioinvasion and tissue necrosis. When present in the orbit,
mucormycosis can quickly lead to permanent visual loss and potentially fatal
cerebral extension. Orbital involvement is almost universally preceded by
infection of the paranasal sinuses. Secondary infection of the orbit via direct
extension of neighboring cutaneous mucormycosis has not been previously
described. The authors present a case of cutaneous mucormycosis with orbital
extension in a poorly controlled diabetic patient.
PMID- 25853502
TI - Gambogic acid induces apoptosis in diffuse large B-cell lymphoma cells via
inducing proteasome inhibition.
AB - Resistance to chemotherapy is a great challenge to improving the survival of
patients with diffuse large B-cell lymphoma (DLBCL), especially those with
activated B-cell-like DLBCL (ABC-DLBCL). Therefore it is urgent to search for
novel agents for the treatment of DLBCL. Gambogic acid (GA), a small molecule
derived from Chinese herb gamboges, has been approved for Phase II clinical trial
for cancer therapy by Chinese FDA. In the present study, we investigated the
effect of GA on cell survival and apoptosis in DLBCL cells including both GCB-
and ABC-DLBCL cells. We found that GA induced growth inhibition and apoptosis of
both GCB- and ABC-DLBCL cells in vitro and in vivo, which is associated with
proteasome malfunction. These findings provide significant pre-clinical evidence
for potential usage of GA in DLBCL therapy particularly in ABC-DLBCL treatment.
PMID- 25853504
TI - Granulocytic Sarcoma of the Orbit Presenting as a Fulminant Orbitopathy in an
Adult With Acute Myeloid Leukemia.
AB - A 64-year-old woman with relapsed acute myelogenous leukemia (AML) undergoing
salvage chemotherapy developed rapid onset of right-sided ophthalmoplegia,
proptosis, optic neuropathy, and vision loss from 20/30 to hand motions over a 3
hour period on day 4 of her treatment. CT scan of her orbits revealed a
superolateral orbital mass and periocular edema. She underwent immediate
canthotomy and cantholysis, and lateral orbitotomy with debulking of the mass
later the same day. The histopathology was consistent with aggregates of myeloid
blasts. Her vision recovered to 20/20 on postoperative day 1. Orbital
granulocytic sarcoma is a rare condition often concurrent with AML, typically in
the pediatric population and rarely in adults. Presentation as a fulminant
orbitopathy with rapidly progressive optic neuropathy and vision loss over
several hours has not been previously reported.
PMID- 25853505
TI - Topical Imiquimod in the Treatment of Conjunctival Actinic Keratosis.
AB - Conjunctival actinic keratosis is rare and difficult to treat, as recurrences are
common. Imiquimod, an immune response modulator, is currently Food and Drug
Administration-approved for cutaneous actinic keratosis and superficial basal
cell carcinomas. Emerging reports have shown it to be effective in treating some
periocular and conjunctival lesions. The authors present a case of a 68-year-old
white man with recurrent actinic keratosis involving the pretarsal conjunctiva,
which was successfully treated with 5% topical imiquimod following previous
failure with cryotherapy and interferon alpha-2b. The patient had ocular
irritation that resolved on cessation of treatment. To the authors' knowledge,
this is the first report of conjunctival actinic keratosis being treated with and
successfully eradicated by topical imiquimod.
PMID- 25853506
TI - Diode Laser-Assisted Endocanalicular Dacryocystorhinostomy: A Prospective Study.
AB - PURPOSE: To evaluate the efficacy of the diode laser in endocanalicular
dacryocystorhinostomy. METHODS: A prospective, noncomparative, interventional
case series using the diode laser for endocanalicular dacryocystorhinostomy in
patients with tearing and nasolacrimal duct obstruction. Outcome measures
included subjective tearing complaints and objective patency of the nasolacrimal
system. Success was defined as improvement of symptoms with patency of
nasolacrimal drainage. Patients were followed for 12 months. Institutional review
board approval was obtained. RESULTS: Forty eyes (28 unilateral, 6 bilateral)
underwent surgery. Five cases were excluded because of inadequate follow-up.
Patients ranged in age from 27 to 88 years (66.7 +/- 15.7). Seventy-seven percent
were female and 23% were male. At 1 week, 88% had improvement in tearing, 12% had
no change or worsening of symptoms, and all patients were patent on irrigation.
At 1 month, 86% had improvement, 14% had no change, and all patients were patent
on irrigation. At 3 months, 83% had improvement and were patent on irrigation.
Seventeen percent had no change or worsening with reflux and were considered
failures. At 6 months, 77% had improvement and were patent on irrigation. Five
additional patients had no change, reflux on exam and were failed surgeries. At
12 months, 74% had complete resolution and were patent. One additional patient
failed. Nine surgeries in 35 cases were considered failures by 12 months.
CONCLUSIONS: Subjective complaints of tearing correlated with patency of the
nasolacrimal system after 3 months. A success rate of 74.3% (26 out of 35 cases)
was observed by 12 months.
PMID- 25853507
TI - The Quantitated Internal Suture Browpexy: Comparison of Two Brow-Lifting
Techniques in Patients Undergoing Upper Blepharoplasty.
AB - PURPOSE: To describe and evaluate 1) the quantitated internal suture browpexy
(ISB), which combines the advantages of a browpexy and "brassiere suture," 2) the
endoscopic Endotine browplasty, and 3) to compare these two techniques in
patients undergoing simultaneous upper blepharoplasty. METHODS: Retrospective
review of patients undergoing bilateral upper blepharoplasty alone, bilateral ISB
with upper blepharoplasty, and bilateral Endotine (MicroAire, Charlottesville,
VA, U.S.A.) browplasty with upper blepharoplasty by one surgeon was performed.
ImageJ 1.47v software (Wayne Rasband, National Institutes of Health, Bethesda,
MD, U.S.A.) and standardized photographs were used to measure pre- and
postoperative brow position at three positions (central, medial, lateral).
Statistical analysis was performed using Sigmaplot version 12.5 for Windows
(Systat Software, Inc., San Jose, CA, U.S.A.). RESULTS: Thirty-three patients
undergoing ISB with blepharoplasty, 33 undergoing Endotine browplasty with
blepharoplasty, and 30 patients undergoing blepharoplasty alone were included.
The 3 groups were matched for age and gender. Patients undergoing upper
blepharoplasty alone showed statistically significant brow descent at all three
brow positions (mean: -1.7 mm [p <= 0.04]). The quantitated ISB prevented brow
descent but provided minimal brow elevation (mean lateral elevation: right eye
(OD) +1.3 mm [p = 0.03]; OS +0.9 mm [p = 0.08]). Endotine browplasty with upper
blepharoplasty provided significant brow elevation at all brow positions,
particularly laterally (OD +4.0 mm [p < 0.001]; OS +3.5 mm [p < 0.001]). There
were no complications. CONCLUSIONS: Upper blepharoplasty alone is associated with
brow descent; performing ISB simultaneously effectively prevents this descent.
Endotine browplasty with upper blepharoplasty achieves significant brow
elevation. Quantitation of the browpexy allows reproducible placement of the
suture thereby producing consistent and symmetrical results.
PMID- 25853508
TI - C5-azobenzene-functionalized locked nucleic acid uridine: isomerization
properties, hybridization ability, and enzymatic stability.
AB - Oligonucleotides (ONs) modified with a locked nucleic acid (LNA) are widely used
in the fields of therapeutics, diagnosis, and nanotechnology. There have been
significant efforts towards developing LNA analogues bearing modified bridges to
improve their hybridization ability, nuclease resistance, and pharmacokinetic
profiles. Moreover, nucleobase modifications of LNA are useful strategies for the
functionalization of ONs. Modifications of the C5-position of pyrimidine
nucleobases are particularly interesting because they enable predictable
positioning of functional groups in the major groove of the duplex. Here we
report the synthesis of C5-azobenzene-functionalized LNA uridine (LNA-U(Az)) and
properties of LNA-U(Az)-modified ONs, including isomerization properties,
hybridization ability, and enzyme stability. LNA-U(Az) in ON is photo-isomerized
effectively and reversibly by irradiation at 365 nm (trans to cis) and 450 nm
(cis to trans). LNA-U(Az)-modified ONs show RNA-selective hybridization ability
despite the large hydrophobic azobenzene moiety extending into the major groove
of the duplex. The enzymatic stability of LNA-U(Az)-modified ONs is higher than
that of natural and LNA-modified ONs with or without photo-irradiation. Our
results indicate that LNA-U(Az) holds promise for RNA targeting and photo
switchable technologies.
PMID- 25853509
TI - Therapeutic effects of topical netrin-4 inhibits corneal neovascularization in
alkali-burn rats.
AB - Netrins are secreted molecules involved in axon guidance and angiogenesis.
However, the role of netrins in the vasculature remains unclear. Netrin-4 and
netrin-1 have been found to be either pro- or antiangiogenic factors. Previously,
we found that netrin-1 acts as an anti-angiogenic factor in rats by inhibiting
alkali burn-induced corneal neovascularization. Here, we further investigate the
effects of netrin-4, another member of the same netrin family, on
neovascularization in vitro and in vivo. We found that netrin-4 functions
similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that
netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation,
viability and proliferation, apoptosis, migration, and invasion in a dose
dependent manner. Netrin-4 was topically applied in vivo to alkali-burned rat
corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin-4
subsequently suppressed and reversed corneal neovascularization. Netrin-4
inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular
endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor
(PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and
macrophage infiltration. These results indicate that netrin-4 shed new light on
its potential roles in treatmenting for angiogenic diseases that affect the
ocular surface, as well as other tissues.
PMID- 25853510
TI - Expectant parents' understanding of the implications and management of fever in
the neonate.
AB - OBJECTIVE: We estimated the extent to which Canadian expectant parents would seek
medical care in a febrile neonate (age 30 days or less). We also evaluated
expectant parents' knowledge of signs and symptoms of fever in a neonate, and
explored the actions Canadian expectant parents would take to optimize the health
of their child. METHODS: We conducted a cross-sectional survey of a sample of
expectant parents from a large urban center in Canada. We recruited participants
from waiting rooms in an obstetrical ultrasound clinic located in an urban
tertiary care hospital in Montreal, Canada. We asked participants nine questions
about fever in neonates including if, and how, they would seek care for their
neonate if they suspected he/she were febrile. RESULTS: Among the 355
respondents, (response rate 87%) we found that 75% of parents reported that they
would take their febrile neonate for immediate medical assessment, with nearly
one fifth of the sample reporting that they would not seek medical care. We found
no significant associations between the choice to seek medical care and expectant
parents socio-demographic characteristics. CONCLUSIONS: Despite universal access
to high quality health care in Canada, our study highlights concerning gaps in
the knowledge of the care of the febrile infant in one fifth of expectant
parents. Physicians and health providers should strive to provide early education
to expectant parents about how to recognize signs of fever in the neonate and how
best to seek medical care. This may improve neonatal health outcomes in Canada.
PMID- 25853511
TI - The Maternal and Child Health (MCH) handbook in Mongolia: a cluster-randomized,
controlled trial.
AB - OBJECTIVE: To assess the effectiveness of the Maternal and Child Health (MCH)
handbook in Mongolia to increase antenatal clinic attendance, and to enhance
health-seeking behaviors and other health outcomes. METHODS: A cluster randomized
trial was conducted using the translated MCH handbook in Bulgan, Mongolia to
assess its effectiveness in promoting antenatal care attendance. Pregnant women
were recruited from 18 randomly allocated districts using shuffled, sealed
envelopes. The handbook was implemented immediately for women at their first
antenatal visit in the intervention group, and nine months later in the control
group. The primary outcome was the number of antenatal care visits of all women
residing in the selected districts. Cluster effects were adjusted for using
generalized estimation equation. Masking was not possible among care providers,
pregnant women and assessors. FINDINGS: Nine districts were allocated to the
intervention group and the remainder to the control group. The intervention group
(253 women) attended antenatal clinics on average 6*9 times, while the control
group (248 women) attended 6*2 times. Socioeconomic status affected the frequency
of clinic attendance: women of higher socioeconomic status visited antenatal
clinics more often. Pregnancy complications were more likely to be detected among
women using the handbook. CONCLUSION: The MCH handbook promotes continuous care
and showed an increase in antenatal visits among the intervention group. The
intervention will help to identify maternal morbidities during pregnancy and
promote health-seeking behaviors. TRIAL REGISTRATION: UMIN Clinical Trial
Registry UMIN000001748.
PMID- 25853512
TI - Tribenzodecacyclene and hexabenzodecacyclene.
AB - High-temperature, TiCl4-catalyzed, triple aldol condensations of aceanthrenone 5
and acenaphthacenone 6 gave tribenzodecacyclene 3 and hexabenzodecacyclene 4,
respectively, in yields of 16 and 0.8%, respectively. Compound 3 is a red,
crystalline solid that is stable under ordinary conditions; its X-ray structure
reveals it to be a strongly pitched, C3-symmetric, molecular propeller. In
contrast, the more highly strained compound 4 is a blue-black solid whose
solutions are unstable to air and light. Its simple NMR spectra, as well as HDFT
calculations, indicate that it is a D3-symmetric molecular propeller.
PMID- 25853513
TI - Comparative analysis of cystatin superfamily in platyhelminths.
AB - The cystatin superfamily is comprised of cysteine proteinase inhibitors and
encompasses at least 3 subfamilies: stefins, cystatins and kininogens. In this
study, the platyhelminth cystatin superfamily was identified and grouped into
stefin and cystatin subfamilies. The conserved domain of stefins (G, QxVxG) was
observed in all members of platyhelminth stefins. The three characteristics of
cystatins, the cystatin-like domain (G, QxVxG, PW), a signal peptide, and one or
two conserved disulfide bonds, were observed in platyhelminths, with the
exception of cestodes, which lacked the conserved disulfide bond. However, it is
noteworthy that cestode cystatins had two tandem repeated domains, although the
second tandem repeated domain did not contain a cystatin-like domain, which has
not been previously reported. Tertiary structure analysis of Taenia solium
cystatin, one of the cestode cystatins, demonstrated that the N-terminus of T.
solium cystatin formed a five turn alpha-helix, a five stranded beta-pleated
sheet and a hydrophobic edge, similar to the structure of chicken cystatin.
Although no conserved disulfide bond was found in T. solium cystatin, the models
of T. solium cystatin and chicken cystatin corresponded at the site of the first
disulfide bridge of the chicken cystatin. However, the two models were not
similar regarding the location of the second disulfide bridge of chicken
cystatin. These results showed that T. solium cystatin and chicken cystatin had
similarities and differences, suggesting that the biochemistry of T. solium
cystatin could be similar to chicken cystatin in its inhibitory function and that
it may have further functional roles. The same results were obtained for other
cestode cystatins. Phylogenetic analysis showed that cestode cystatins
constituted an independent clade and implied that cestode cystatins should be
considered to have formed a new clade during evolution.
PMID- 25853514
TI - Lucy Montoro Rehabilitation Network mobile unit: an alternative public healthcare
policy.
AB - PURPOSE: The aim is to analyze rehabilitation services provided by a mobile
rehabilitation clinic (MU) in nine regions of the State of Sao Paulo,
demonstrating the distribution of orthoses, prostheses and other mobility aids
for persons with physical disabilities according to age groups and impairments,
as well as the number of persons with physical disabilities as estimated by
Brazilian official data sources. METHOD: The number of persons with disabilities
in each region was obtained through estimations from the 2010 Brazilian IBGE
Census. The number of assistive technologies suppliers and technicians were
provided by the Brazilian Technical Orthopedics Association (ABOTEC). Patients
were referred to the MU by Regional Health Departments. After examination of a
multidisciplinary team, assistive devices are prescribed and delivered according
to patients' needs. Data on patients were also assessed according to
questionnaires on their age, diagnosis, gender, marital status and education
level. RESULTS: From 2009 to 2011, the MU went through 15,000 km providing
rehabilitation services through the Public Health System to 1801 patients.
Additionally, 3328 devices were delivered in this period. Different age,
diagnosis, gender, marital status and schooling profiles are highlighted in each
of the analyzed regions. CONCLUSION: Data on patients' profiles were made
available through services provided by the MU--including the average index of
1.85 devices delivered to each patient and demand projections--which can be used
in the planning of public policies. The MU made rehabilitation services more
accessible, trained professionals, raised awareness on the correct delivery and
use of assistive devices, and identified and organized people's demand in each
region. Implications for Rehabilitation Delivering prostheses, orthoses and other
mobility aids fulfills the rights of persons with disabilities to personal
mobility with the greatest possible independence, as foreseen by the Convention
on the Rights of Persons with Disabilities, increasing their participation in
society on an equal basis with others. The direct impact of actively reaching out
into the community to provide quality rehabilitation services and assistive
devices increases the level of access of persons with disabilities to health
services and equalizes opportunities. Outreach initiatives to deliver
rehabilitation services in the community must include a capacity-building
component. Building the capacities of local practitioners and health personnel
will further empower both these professionals and persons with disabilities,
diminishing attitudinal barriers. Reaching out into the community allows
gathering data on the prevalence of health conditions, local need and demand for
assistive devices and rehabilitation services, and informs decision-making.
PMID- 25853515
TI - Functional genomics screening utilizing mutant mouse embryonic stem cells
identifies novel radiation-response genes.
AB - Elucidating the genetic determinants of radiation response is crucial to
optimizing and individualizing radiotherapy for cancer patients. In order to
identify genes that are involved in enhanced sensitivity or resistance to
radiation, a library of stable mutant murine embryonic stem cells (ESCs), each
with a defined mutation, was screened for cell viability and gene expression in
response to radiation exposure. We focused on a cancer-relevant subset of over
500 mutant ESC lines. We identified 13 genes; 7 genes that have been previously
implicated in radiation response and 6 other genes that have never been
implicated in radiation response. After screening, proteomic analysis showed
enrichment for genes involved in cellular component disassembly (e.g. Dstn and
Pex14) and regulation of growth (e.g. Adnp2, Epc1, and Ing4). Overall, the best
targets with the highest potential for sensitizing cancer cells to radiation were
Dstn and Map2k6, and the best targets for enhancing resistance to radiation were
Iqgap and Vcan. Hence, we provide compelling evidence that screening mutant ESCs
is a powerful approach to identify genes that alter radiation response.
Ultimately, this knowledge can be used to define genetic variants or therapeutic
targets that will enhance clinical therapy.
PMID- 25853516
TI - Prevalence of asthma and allergic rhinitis among adults in Yaounde, Cameroon.
AB - BACKGROUND: Population-based estimates of asthma and allergic rhinitis in sub
Saharan African adults are lacking. We assessed the prevalence and determinants
of asthma and allergic rhinitis in urban adult Cameroonians. METHODS: A community
based survey was conducted from December 2013 to April 2014 among adults aged 19
years and above (N = 2,304, 57.3% women), selected through multilevel stratified
random sampling across all districts of Yaounde (Capital city). Internationally
validated questionnaires were used to investigate the presence of allergic
diseases. Logistic regressions were employed to investigate the determinants of
allergic conditions. RESULTS: Prevalence rates were 2.7% (95% CI: 2.1-3.4) for
asthma-ever, 6.9% (5.9-7.9) for lifetime wheezing, 2.9% (92.2-3.6) for current
wheezing and 11.4% (10.1-12.7) for self-reported lifetime allergic rhinitis;
while 240 (10.4%) participants reported current symptoms of allergic rhinitis,
and 125 (5.4%) had allergic rhino-conjunctivitis. The prevalence of current
asthma medication use and self-reported asthma attack was 0.8 (0.4-1.2) and 1
(0.6-1.4) respectively. Multivariable adjusted determinants of current wheezing
were signs of atopic eczema [2.91 (1.09-7.74)] and signs of allergic rhinitis
[3.24 (1.83-5.71)]. Age group 31-40 years [0.27(0.09-0.78), p = 0.016] was an
independent protective factor for wheezing. Determinants of current rhinitis
symptoms were active smoking [2.20 (1.37-3.54), p<0.001], signs of atopic eczema
[2.84 (1.48-5.46)] and current wheezing [3.02 (1.70-5.39)]. CONCLUSION:
Prevalence rates for asthma and allergic rhinitis among adults in this population
were at the lower tails of those reported in other regions of the world. Beside
the classical interrelation between allergic diseases found in this study, active
smoking was an independent determinant of allergic rhinitis symptoms. Nationwide
surveys are needed to investigate regional variations.
PMID- 25853517
TI - Phosphine resistance in India is characterised by a dihydrolipoamide
dehydrogenase variant that is otherwise unobserved in eukaryotes.
AB - Phosphine (PH3) fumigation is the primary method worldwide for controlling insect
pests of stored commodities. Over-reliance on phosphine, however, has led to the
emergence of strong resistance. Detailed genetic studies previously identified
two loci, rph1 and rph2, that interact synergistically to create a strong
resistance phenotype. We compared the genetics of phosphine resistance in strains
of Rhyzopertha dominica and Tribolium castaneum from India and Australia,
countries having similar pest species but widely differing in pest management
practices. Sequencing analysis of the rph2 locus, dihydrolipoamide dehydrogenase
(dld), identified two structurally equivalent variants, Proline49>Serine (P49S)
in one R. dominica strain and P45S in three strains of T. castaneum from India.
These variants of the DLD protein likely affect FAD cofactor interaction with the
enzyme. A survey of insects from storage facilities across southern India
revealed that the P45/49S variant is distributed throughout the region at very
high frequencies, in up to 94% of R. dominica and 97% of T. castaneum in the
state of Tamil Nadu. The abundance of the P45/49S variant in insect populations
contrasted sharply with the evolutionary record in which the variant was absent
from eukaryotic DLD sequences. This suggests that the variant is unlikely to
provide a strong selective advantage in the absence of phosphine fumigation.
PMID- 25853518
TI - Chromosomal patterns of diversity and differentiation in creepers: a next-gen
phylogeographic investigation of Certhia americana.
AB - With methods for sequencing thousands of loci for many individuals,
phylogeographic studies have increased inferential power and the potential for
applications to new questions. In songbirds, strong patterns of inter-chromosomal
synteny, the published genome of a songbird and the ability to obtain thousands
of genetic loci for many individuals permit the investigation of differentiation
between and diversity within lineages across chromosomes. Here, we investigate
patterns of differentiation and diversity in Certhia americana, a widespread
North American songbird, using next-generation sequencing. Additionally, we
reassess previous phylogeographic studies within the group. Based on ~30 million
sequencing reads and more than 16,000 single-nucleotide polymorphisms in 41
individuals, we identified a strong positive relationship between genetic
differentiation and chromosome size, with a negative relationship between genetic
diversity and chromosome size. A combination of selection and drift may explain
these patterns, although we found no evidence for selection. Because the observed
genomic patterns are very similar between widespread, allopatric clades, it is
unlikely that selective pressures would be so similar across such different
ecological conditions. Alternatively, the accumulation of fixed differences
between lineages and loss of genetic variation within lineages due to genetic
drift alone may explain the observed patterns. Due to relatively higher
recombination rates on smaller chromosomes, larger chromosomes would, on average,
accumulate fixed differences between lineages and lose genetic variation within
lineages faster, leading to the patterns observed here in C. americana.
PMID- 25853519
TI - Incidence of type 2 diabetes in pre-diabetic Japanese individuals categorized by
HbA1c levels: a historical cohort study.
AB - OBJECTIVE: Reported incidence of type 2 diabetes estimated at the pre-diabetic
stage differs widely (2.3-18.1% per year). Because clinicians need to know the
risk of incident diabetes after a diagnosis of pre-diabetes, our objective was to
estimate precise incidence of diabetes using baseline HbA1c levels. METHODS: A
historical cohort study using electronic medical record data obtained between
January 2008 and December 2013. A total of 52,781 individuals with HbA1c < 6.5%
were assigned to one of six groups categorized by baseline HbA1c level: <= 5.5%
(n=34,616), 5.6-5.7% (n=9,388), 5.8-5.9% (n=4,664), 6.0-6.1% (n= 2,338), 6.2-6.3%
(n=1,257), and 6.4% (n=518). Participants were tracked until a subsequent
diagnosis of diabetes or end of follow-up during a period of 5 years. RESULTS:
During the follow-up period (mean 3.7 years), 4,369 participants developed
diabetes. The incidence of diabetes in the first year was 0.7, 1.5, 2.9, 9.2,
30.4, and 44.0% in the six HbA1c groups, respectively. At five years the
incidence was 3.6, 8.9, 13.8, 27.5, 51.6, and 67.8%, respectively (p < 0.0001
comparing the HbA1c <=5.5% group to the other groups). After adjustment for
confounding factors, the hazard ratios compared with the HbA1c <=5.5% group were
significantly elevated: 2.3 (95%CI 2.0-2.5), 3.4 (95%CI 2.9-3.7), 8.8 (95%CI 8.0
10.1), 26.3 (95%CI 23.3-30.1), and 48.7 (95%CI 40.8-58.1) in the five HbA1c
groups (p < 0.0001). CONCLUSION: By fractionating baseline HbA1c levels into
narrower HbA1c range groups, accuracy of estimating the incidence of type 2
diabetes in subsequent years was increased. The risk of developing diabetes
increased with increasing HbA1c levels, especially with the HbA1c level >= 6.2%
in the first follow-up year.
PMID- 25853520
TI - Economic behavior under the influence of alcohol: an experiment on time
preferences, risk-taking, and altruism.
AB - We report results from an incentivized laboratory experiment undertaken with the
purpose of providing controlled evidence on the causal effects of alcohol
consumption on risk-taking, time preferences and altruism. Our design
disentangles the pharmacological effects of alcohol intoxication from those
mediated by expectations, as we compare the behavior of three groups of subjects:
those who participated in an experiment with no reference to alcohol, those who
were exposed to the possibility of consuming alcohol but were given a placebo and
those who effectively consumed alcohol. All subjects participated in a series of
economic tasks administered in the same sequence across treatments. After
controlling for both the willingness to pay for an object and the potential
misperception of probabilities as elicited in the experiment, we detect no effect
of alcohol in depleting subjects' risk tolerance. However, we find that alcohol
intoxication increases impatience and makes subjects less altruistic.
PMID- 25853522
TI - The effect of lentiviral vector-mediated RNA interference targeting hypoxia
inducible factor 1alpha on the uptake of fluorodeoxyglucose ((18)f) in the human
pancreatic cancer cell line, patu8988.
AB - Hypoxia can stimulate (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in cultured
tumor cells. This study has investigated the effect of lentiviral vector-mediated
RNA interference (RNAi) targeting hypoxia-inducible factor 1alpha (HIF-1alpha) on
the changes in HIF-1 and glucose transporter 1 (Glut-1) expression, the cell
growth, and the uptake of (18)F-FDG in the human pancreatic cancer cell line,
Patu8988. Lentiviral RNAi vector targeting the HIF-1alpha gene (LV-HIF
1alphaRNAi) was constructed and used to treat cells at various concentrations (25
200 nM). The expression changes of HIF-1alpha and Glut-1 in hypoxic Patu8988
cells after RNAi treatment were determined using real time reverse transcription
polymerase chain reaction (real-time PCR). The inhibition rate of cell
proliferation 48 hours after the addition of 10 MUL of different concentrations
of LV-HIF-1alphaRNAi (25-200 nM) was assayed using the MTT method. Meanwhile, the
cell uptake of (18)F-FDG was also assessed. After RNAi transfection, the relative
expression levels of HIF-1alpha mRNA and Glut-1 under hypoxia were reduced and
the relative expression levels of HIF-1alpha protein also decreased. Compared
with the control group, the inhibition rates of cell proliferation under
different viral dosages were 5.98%, 15.65%, 26.42%, and 40.81%, respectively,
positively correlated with the viral doses (r=0.558, p<0.05). Under hypoxia, Glut
1 mRNA expression in Patu8988 cells treated with 200 nM of LV-HIF-1alphaRNAi for
24, 48, and 72 hours, respectively, was positively correlated with the inhibition
rate of cell proliferation (r=0.618, p<0.05) as well as the inhibition rate of
(18)F-FDG uptake (r=0.664, p<0.05), while the latter two displayed a positive
correlation with each other too (r=0.582, p<0.05). Under hypoxia, RNAi targeting
HIF-1alpha significantly inhibited the expression of Glut-1 mRNA in Patu8988
pancreatic cancer cells and their uptake of (18)F-FDG. These results suggest that
LV-HIF-1alphaRNAi may form a new treatment for pancreatic cancer, and the
effectiveness of the treatment can be readily assessed with (18)F-FDG imaging.
PMID- 25853523
TI - Serotonin's many meanings elude simple theories.
PMID- 25853521
TI - Coxsackievirus A16 elicits incomplete autophagy involving the mTOR and ERK
pathways.
AB - Autophagy is an important homeostatic process for the degradation of cytosolic
proteins and organelles and has been reported to play an important role in
cellular responses to pathogens and virus replication. However, the role of
autophagy in Coxsackievirus A16 (CA16) infection and pathogenesis remains
unknown. Here, we demonstrated that CA16 infection enhanced autophagosome
formation, resulting in increased extracellular virus production. Moreover,
expression of CA16 nonstructural proteins 2C and 3C was sufficient to trigger
autophagosome accumulation by blocking the fusion of autophagosomes with
lysosomes. Interestingly, we found that Immunity-related GTPase family M (IRGM)
was crucial for the activation of CA16 infection-induced autophagy; in turn,
reducing IRGM expression suppressed autophagy. Expression of viral protein 2C
enhanced IRGM promoter activation, thereby increasing IRGM expression and
inducing autophagy. CA16 infection inhibited Akt/mTOR signaling and activated
extracellular signal-regulated kinase (ERK) signaling, both of which are
necessary for autophagy induction. In summary, CA16 can use autophagy to enhance
its own replication. These results raise the possibility of targeting the
autophagic pathway for the treatment of hand, foot, and mouth disease (HFMD).
PMID- 25853524
TI - Plasma Kallikrein Inhibitors in Cardiovascular Disease: An Innovative Therapeutic
Approach.
AB - Plasma prekallikrein is the liver-derived precursor of the trypsin-like serine
protease plasma kallikrein, and circulates in plasma bound to high molecular
weight kininogen. Plasma prekallikrein is activated to plasma kallikrein by
activated factor XII or prolylcarboxypeptidase. Plasma kallikrein regulates the
activity of multiple proteolytic cascades in the cardiovascular system such as
the intrinsic pathway of coagulation, the kallikrein-kinin system, the
fibrinolytic system, the renin-angiotensin system, and the complement pathways.
As such, plasma kallikrein plays a central role in the pathogenesis of
thrombosis, inflammation, and blood pressure regulation. Under physiological
conditions, plasma kallikrein serves as a cardioprotective enzyme. However, its
increased plasma concentration or hyperactivity perpetuates cardiovascular
disease (CVD). In this article, we review the biochemistry and cell biology of
plasma kallikrein and summarize data from preclinical and clinical studies that
have established important functions of this serine protease in CVD states.
Finally, we propose plasma kallikrein inhibitors as a novel class of drugs with
potential therapeutic applications in the treatment of CVDs.
PMID- 25853526
TI - Income disparity and student career choice.
PMID- 25853527
TI - Family medicine resident billing and lost revenue: a regional cross-sectional
study.
AB - BACKGROUND AND OBJECTIVES: The financial margins for primary care clinics and
residencies are narrow. It is important that residents bill properly for
educational and financial purposes as well as for compliance. This study compares
resident and attending Evaluation and Management (E&M) coding from family
medicine residency programs across a five-state region, with established billing
benchmarks. METHODS: We collected established visit E&M codes for faculty and
residents from a network of family medicine residencies in the Northwest United
States over a 6-month period. Aggregated codes were compared to billing
benchmarks from the Medical Group Management Association (MGMA) to estimate
effects on revenue from these visits. RESULTS: We obtained coding data for
131,788 established problem-focused visits from 353 residents and 186 faculty
physicians in 16 of 18 eligible family medicine residencies. Both residents and
faculty billed lower numbers of high complexity codes than MGMA benchmarks. PGY
1s coded higher numbers of high complexity codes than PGY-3s. Annual estimated
revenue loss was $481,654 for the programs overall. CONCLUSIONS: Residents do not
bill established visits at the level of generally accepted benchmarks, which
contributes to significant financial losses for programs and carries regulatory
implications. The reasons for incorrect billing need to be established and
interventions developed to overcome these barriers.
PMID- 25853525
TI - Epileptogenic but MRI-normal perituberal tissue in Tuberous Sclerosis Complex
contains tuber-specific abnormalities.
AB - INTRODUCTION: Recent evidence has implicated perituberal, MRI-normal brain tissue
as a possible source of seizures in tuberous sclerosis complex (TSC). Data on
aberrant structural features in this area that may predispose to the initiation
or progression of seizures are very limited. We used immunohistochemistry and
confocal microscopy to compare epileptogenic, perituberal, MRI-normal tissue with
cortical tubers. RESULTS: In every sample of epileptogenic, perituberal tissue,
we found many abnormal cell types, including giant cells and cytomegalic neurons.
The majority of giant cells were surrounded by morphologically abnormal
astrocytes with long processes typical of interlaminar astrocytes. Perituberal
giant cells and astrocytes together formed characteristic "microtubers". A
parallel analysis of tubers showed that many contained astrocytes with features
of both protoplasmic and gliotic cells. CONCLUSIONS: Microtubers represent a
novel pathognomonic finding in TSC and may represent an elementary unit of
cortical tubers. Microtubers and cytomegalic neurons in perituberal parenchyma
may serve as the source of seizures in TSC and provide potential targets for
therapeutic and surgical interventions in TSC.
PMID- 25853528
TI - Beyond diagnoses: family medicine core themes in student reflective writing.
AB - BACKGROUND AND OBJECTIVES: We share qualitative study results of third-year
medical student writings during their family medicine clerkship utilizing a
reflective writing exercise from 2005 and 2013. METHODS: For this paper, 50
student writings were randomly selected from the 2005 cohort in addition to 50
student writings completed by the 2013 cohort. Deductive thematic analysis
utilizing Atlas.ti software was completed utilizing the Future of Family Medicine
core attributes of family physicians as the a priori coding template. RESULTS:
Student writings actively reflect key attributes of family physicians as
described by the Future of Family Medicine Report: a deep understanding of the
dynamics of the whole person, a generative impact on patients' lives, a talent
for humanizing the health care experience, and a natural command of complexity
and multidimensional access to care. CONCLUSIONS: We discuss how to lead the
writing exercise and provide suggestions for facilitating the discussion to bring
out these important aspects of family medicine care.
PMID- 25853529
TI - Are nonphysician health care providers prepared and supported to teach in family
medicine?
AB - BACKGROUND AND OBJECTIVES: Understanding how nonphysician health care providers
(NPHCPs) teach medical trainees is integral to optimizing family medicine
education. The objective of this study was to examine the teaching roles, level
of preparation and support, and the challenges encountered by NPHCPs. METHODS: A
cross-sectional web-based survey of NPHCPs was conducted across academic teaching
units affiliated with the University of Toronto's Department of Family and
Community Medicine (DFCM). The level of preparation for educational roles,
perceived support, challenges encountered, and educational training needs of
NPHCPs were examined. Variables associated with preparedness to teach were also
identified. RESULTS: Of the 193 NPHCPs surveyed, 166 (86%) completed the
questionnaire. A total of 126 (82%) of NPHCP educators (nurses, social workers,
dietitians, and pharmacists) reported teaching medical trainees. Most did not
hold faculty appointments. The majority had no formal training in teaching, and
less than half felt prepared for their academic responsibilities. NPHCPs
perceived a lack of support for their teaching. NPHCPs also identified
predictable challenges such as lack of time and lack of funding. Challenges
specific to cross-professional teaching were also identified. NPHCPs expressed an
interest in receiving continuing education to improve their teaching skills.
NPHCPs' self-reported level of preparedness to teach was variable and associated
with years of teaching experience, information received about trainees,
challenges faced, and continuing education needs. CONCLUSIONS: NPHCPs are
extensively involved in teaching medical trainees. There is variability in their
preparation level, and they encounter significant challenges. To advance
effective and sustainable inter-professional education (IPE) within family
medicine, addressing these issues is crucial.
PMID- 25853530
TI - Personality profiles of rural longitudinal integrated clerkship students who
choose family medicine.
AB - BACKGROUND AND OBJECTIVES: Physician workforce projections fuel interest in
addressing the shortage of family physicians. Copious research has investigated
personality as a variable influencing specialty intention. Medical school rural
longitudinal integrated clerkships (LICs) nurture interest in family medicine.
This study examined whether rural LIC students who intended to and eventually
matched into family medicine portrayed a personality trait profile different from
rural LIC students who intended or matched to all other specialities. The
profiles of four successive cohorts are described in relation to their intended
and eventual specialty match. METHODS: A cross-sectional design sampled 145 third
year students from 2008--2011. A survey measured demographics, temperament and
character personality traits, and Other-Oriented Empathy. Multivariate analysis
compared family medicine versus all other specialty matches and original
specialty intention with eventual match. RESULTS: Match groups did not differ in
gender, age, or marital status. Rural LIC students who matched in family medicine
had lower levels of Harm Avoidance, higher Reward Dependence, and nonsignificant
higher levels of every other personality trait in comparison to other matches.
Rural LIC students who intended and matched to family medicine showed the highest
levels of Reward Dependence (warm sociability) and Other-Oriented Empathy
compared to any other specialty. CONCLUSIONS: Lower levels of Harm Avoidance are
conducive to less anxiety, more composure and confidence in making decisions, and
being relaxed in accepting a degree of risk and uncertainty. Such calm optimism
along with higher Reward Dependence showing social warmth and empathy are
desirable traits for family physicians regularly confronted with a wide range of
presentations from the obvious to complex. Further investigation of what
influences sustainability of the intention to enter family medicine may be useful
to educators for counseling.
PMID- 25853531
TI - Microblog use and student engagement in the large-classroom setting.
AB - BACKGROUND AND OBJECTIVES: Encouraging student engagement in the large-classroom
setting can be difficult. Challenges include the depersonalized nature of the
environment and the fact that students frequently find asking questions and
participating in class discussion intimidating. Social media has the potential to
address these barriers, but this has not yet been formally evaluated. Our study
analyzed the impact of microblog use on students' question-asking behaviors (an
indicator of student engagement) in a large-classroom setting. METHODS: Formative
evaluation of a large-classroom medical humanities course identified microblog
use as a potential tool to facilitate greater student engagement. A microblog was
thereafter incorporated into the course. Student engagement was operationalized
as question-asking behaviors before and after microblog incorporation. RESULTS:
Paired t tests showed that the total number of questions asked was significantly
greater in the microblog-available classes, t (2)=12.12. In addition,
significantly more individual students asked questions in the microblog-available
classes, t (2)=17.39. CONCLUSIONS: Our study, demonstrating an increase in
question-asking behavior after incorporation of a microblog, has important
implications for educators who seek to enhance student engagement and learning in
the large-classroom setting. In addition, innovative use of emerging technologies
(such as microblogs) as educational tools requires continuous assessment and
iterative change to maximize benefit. More research is needed to evaluate what
specific barriers to engagement are overcome by microblog use and whether
microblog use can similarly benefit other courses.
PMID- 25853532
TI - What providers want from the Primary Care Extension Service to facilitate
practice transformation.
AB - BACKGROUND AND OBJECTIVES: While several experts have shared their visions of the
Primary Care Extension Service (PCES) as called for in the Affordable Care Act
(ACA), little is known about providers' perspective. We aimed to identify the
most and least desired resources that primary care providers want from the PCES.
METHODS: A 70-question survey was administered to primary care providers (n=556)
in Pennsylvania, one of four initial states chosen to develop the PCES
infrastructure. Analysis focused on the highest and lowest ranked questions.
RESULTS: The most desired PCES services include (1) identifying and coordinating
mental health services, (2) improving office efficiency, (3) increasing overall
revenues, and (4) strategies to help implement evidence-based clinical
guidelines. The least desired PCES services include (1) implementing e
prescribing, (2) implementing an electronic medical record (EMR) system, (3)
implementing group visits, (4) recruiting new patients, and (5) implementing open
or advanced access scheduling. CONCLUSIONS: Despite expert models presented for
the PCES, there is a critical need to ask primary care providers what they need
from such a service. Our findings identified some divergences from key patient
centered medical home (PCMH) components, including the low ranking of services
related to EMRs and increasing patient access. With interest growing in
developing a PCES that would help spread innovation as outlined in the ACA, it's
important to take a demand-side approach to the services providers most desire
versus the more traditional supply-side approach that assumes the assistance
providers need.
PMID- 25853533
TI - Newborn well-child visits in the home setting: a pilot study in a family medicine
residency.
AB - BACKGROUND: The purpose of our study was to pilot a home visit program targeting
neonates conducted by family medicine residents. While the literature shows that
home visit programs are successful at preventing adverse outcomes for young
children, such as improving parenting practices and promoting breastfeeding, no
data exist about newborn home visits conducted by resident physicians. METHODS:
Residents conducted newborn home visits precepted by a family medicine faculty
member from June 2012--May 2013. Subjects were recruited from the residency
continuity practice and randomized to receive two home visits (which replaced two
office visits) or routine office-based newborn care. All participants were
surveyed using the validated WHOQOL-BREF quality of life scale and a patient
satisfaction instrument. Metrics were also obtained from the electronic medical
record. Mothers and resident physicians completed an open-ended questionnaire
about their experience. RESULTS: All patients, whether receiving office-based or
home-based care, rated their care highly. Significant differences were seen in
usage of acute care in the first 6 months of life, and mothers in the home visit
group trended toward initiating breastfeeding at a higher rate. The home visit
group ranked their quality of life higher across all domains when compared to the
control group, approaching statistical significance in two domains. Residents
providing home visits reported increased connectedness to patients and improved
confidence in anticipatory guidance delivery. CONCLUSIONS: Home visits are
valuable for families with newborns, in terms of minimizing acute care service
usage, breastfeeding promotion, and perhaps increasing maternal perceptions of
well-being. A home visit program has the potential to enhance resident education
and the doctor-patient relationship.
PMID- 25853534
TI - Social media beliefs and usage among family medicine residents and practicing
family physicians.
AB - BACKGROUND AND OBJECTIVES: Incorporation of social media (SM) use in medicine is
gaining support. The Internet is now a popular medium for people to solicit
medical information. Usage of social networks, such as Facebook and Twitter, is
growing daily and provides physicians with nearly instantaneous access to large
populations for both marketing and patient education. The benefits are myriad,
but so are the inherent risks. We investigated the role providers' age and
medical experience played in their beliefs and use of SM in medicine. METHODS:
Using multiple state-wide and national databases, we assessed social media use by
family medicine residents, faculty, and practicing family physicians with a 24
question online survey. Descriptive data is compared by age and level of medical
experience. RESULTS: A total of 61 family medicine residents and 192 practicing
family physicians responded. There is a trend toward higher SM utilization in the
younger cohort, with 90% of resident respondents reporting using SM, half of them
daily. A total of 64% of family physician respondents over the age of 45 have a
SM account. An equal percentage of senior physicians use SM daily or not at all.
Practicing physicians, more than residents, agree that SM can be beneficial in
patient care. The vast majority of residents and physicians polled believe that
SM should be taught early in medical education. CONCLUSIONS: The high utilization
of SM by younger providers, high prevalence of patient use of the Internet, and
the countless beneficial opportunities SM offers should be catalysts to drive
curriculum development and early implementation in medical education. This
curriculum should focus around four pillars: professional standards for SM use,
SM clinical practice integration, professional networking, and research.
PMID- 25853535
TI - Students do not reduce patient satisfaction in a family medicine clinic as
measured by a nationally used patient satisfaction instrument.
AB - BACKGROUND AND OBJECTIVES: Patient satisfaction surveys are widely used to give
physicians feedback on their treatment of patients, included in physician
performance evaluation and payment, and correlated with better health outcomes.
Our research uses industry-standard satisfaction measures to gauge the impact on
patient satisfaction of having students involved in a patient's medical care at
the family medicine clinic of a large southwestern osteopathic medical school.
METHODS: A retrospective cohort study was conducted using the Press-Ganey Survey,
a national survey commonly used by hospitals and clinics. The survey was modified
to indicate the presence of a learner in the patient's treatment room. The survey
provided data on patient satisfaction with the office, the visit, and the care
received. RESULTS: Overall, 730 survey responses were used in the study, 434 from
patients with whose visit included a student. There were no statistically
significant differences in patient satisfaction scores, including overall
satisfaction with the visit. CONCLUSIONS: Our findings indicate that student
doctors do not decrease patient satisfaction and that satisfaction scores may be
useful in student evaluations. This finding should encourage outpatient
physicians who teach medical students that their patient satisfaction scores on
the most widely used patient satisfaction survey will not be impacted by teaching
students.
PMID- 25853536
TI - Time to change our paradigm for faculty recruitment; old rules are failing us: we
need to recruit new faculty before they graduate.
PMID- 25853538
TI - Updating indicators for scaling the socioeconomic level of families for health
research.
AB - BACKGROUND: Socioeconomic position is a community-used concept in health
research. The social level is related to numerous exposures, resources, and
susceptibilities that may affect health. AIM: To update and validate a tool for
scaling the socioeconomic level of families for health research. PARTICIPANTS AND
METHODS: A multistage stratified cluster sampling technique was used to select
900 families (one index person per family) from urban and rural areas in the
Alexandria governorate using the proportional allocation method. Ten variables
reflecting parental education, parental occupation, family characteristics,
financial status as well as home sanitation were reduced to a single
socioeconomic status (SES) index using two methods: the Sigma scoring method and
factor analysis. Reliability and validity were assessed for the developed scale.
Factor scores were classified into three categories (low, medium, high) using
cluster analysis, and then different cut-off points for the Sigma scoring method
were used and compared with the cluster solution using the kappa statistic.
RESULTS: Results showed that the developed scale was both reliable (Cronbach's
alpha coefficient alpha=0.79) and valid [8 out of the 10 items had high loading
(>0.5) for SES]. The best cut-off points for SES classification using the
proposed scoring system that yielded the highest agreement with the cluster
solution (kappa=0.77) were less than 40%, 40 to <70%, and at 70% or more, with an
overall correct classification of 84.7%. CONCLUSION AND RECOMMENDATION: The new
scale proved to be valid and reliable. This scale is recommended for use for
scaling the socioeconomic level of families for health research.
PMID- 25853537
TI - Dual Emission of a Novel (P,N) Re(I) Complex: A Computational and Experimental
Study on [P,N-{(C6H5)2(C5H4N)P}Re(CO)3Br].
AB - The spectroscopic, electrochemical, and photophysical properties of the new
complex [P,N-{(C6H5)2(C5H4N)P}Re(CO)3Br] are reported. The UV-vis spectrum in
dichloromethane shows an absorption maximum centered at 315 nm and a shoulder at
350 nm. These absorption bands have been characterized to have MLCT character.
Excitation at both wavelengths (maximum and shoulder) leads to an emission band
centered at 550 nm. Cyclic voltammetry experiments show two ill-defined
irreversible oxidation waves around +1.50 and 1.80 V that are assigned to
Re(I)/Re(II) and Re(II)/Re(III) couples whereas an irreversible reduction signal
centered at -1.80 V is likewise assigned to a ligand reduction process. These
results support the proposal of the MLCT nature of the states implied by the
emission of the complex. The luminescent decay fits to a biexponential function,
where the lifetimes and emission quantum yields are dependent on the solvent
polarity. DFT calculations suggest that dpi -> pi*pyridine and dpi -> pi*phenyl
excited states may account for the existence of two decay lifetimes.
PMID- 25853539
TI - Effects of a training program about breast cancer and breast self-examination
among female students at Taif University.
AB - BACKGROUND: Breast cancer is the most common type of cancer in Saudi women. It is
spreading three times faster in the Kingdom than in other countries. One-third of
breast cancers are preventable through healthy life styles. OBJECTIVE: This study
aimed to assess the impact of a training program on breast cancer and breast self
examination (BSE) among female students at Taif University. PARTICIPANTS AND
METHODS: This study was carried out using a pre-post test design on a sample of
female university students from seven colleges in Taif University (Faculty of
Science, Faculty of Economics and Management, Faculty of Art, Faculty of
Education, Faculty of Medicine, Faculty of Pharmacy, and the Faculty of Applied
Medical Sciences) in the academic year 2012-2013. RESULTS: None of the
participants had ever practiced BSE before training, and only 16% of them
believed that BSE is necessary, whereas 8.7% were willing to teach others BSE.
There was limited knowledge of breast cancer. After the training program, a
significant improvement was observed in all knowledge items, and 83.6% of the
students practiced BSE compared with 0% practice before training. CONCLUSION:
This study showed the effectiveness of the intervention program in improving
students' knowledge of breast cancer and their practice of BSE. Thus, campaigns
focusing on females in this age group should be carried out in the Saudi society.
PMID- 25853540
TI - Factors associated with health-related quality of life among patients with liver
cirrhosis in Egypt.
AB - BACKGROUND: Although the disease burden of liver cirrhosis in Egypt is high and
there are few resources for its management, there is limited research on the
health-related quality of life (HRQOL) of Egyptian patients with liver cirrhosis.
AIMS: To describe the HRQOL of liver cirrhotic patients in Egypt and to analyse
factors associated with this construct. PATIENTS AND METHODS: A cross-sectional
study with a convenience sample of 401 patients from three hospitals in Cairo,
Egypt, was carried out in June-August 2011. Patients were interviewed to complete
a background data form, Short Form-36, the Liver Disease Symptom Index-2.0 and
the Multidimensional Scale of Perceived Social Support. RESULTS: Patients had low
HRQOL, with mental health perceived to be poorer than physical health. In
regression analyses, severity of symptoms, disease stage, comorbidities and
employment status were associated significantly with physical health, accounting
for 19% of the variance. For mental health, 31.7% of the variation was explained
by severity of symptoms, employment status and perceived spouse and family
support. CONCLUSION AND RECOMMENDATIONS: These findings highlight the needs of
patients with liver cirrhosis in Egypt. Engaging the patients' family in care
planning may decrease patients' burden and improve their HRQOL. This study also
provides a rationale to develop future research in symptom management to enhance
HRQOL.
PMID- 25853541
TI - Interleukin-4 -590 T>C and interleukin-4 receptor Q551R A>G gene polymorphisms in
Saudi cases with alopecia areata.
AB - OBJECTIVES: Immunogenetic factors are known to play a role in the pathogenesis of
alopecia areata (AA). This study aimed at investigating the association between
AA with the polymorphisms of interleukin-4 (IL-4) promoter and receptor (IL-4R)
genes. PATIENTS AND METHODS: This work is a case-control study that was conducted
on 76 AA patients from Qassim region, Saudi Arabia. Patients were compared with
93 normal healthy controls from the same locality. Genomic DNA was extracted and
processed using real-time PCR amplification for characterization of IL-4 -590 T>C
and IL-4R Q551R A>G gene polymorphisms. RESULTS: Cases of AA showed a higher
frequency of the IL-4 -590 CC homozygous genotype compared with controls (63.2
vs. 53.8%, P>0.05) with a lower frequency of the TT genotype (5.3 vs. 10.8%);
yet, both were statistically nonsignificant (P>0.05). Regarding the IL-4R Q551R
A>G polymorphism, cases and controls showed nearly equal frequencies of all
variants, that is, with no significant difference. Although the frequency of the
IL-4 C and the IL-4R A alleles was higher among cases than among controls (78.9
vs. 71.5% and 78.8 vs. 72.6%, respectively), this was also statistically
nonsignificant (P>0.05). Comparing case subgroups in terms of their age of onset,
sex, disease severity, consanguinity, and family history showed no statistically
significant difference regarding the studied genetic variant. CONCLUSION: IL-4
590 and IL-4R Q551R gene polymorphisms are not associated with the susceptibility
and the clinical pattern of AA in Saudi patients. We recommend further research
studies involving the estimation of cytokines both in the serum and in the local
skin lesions or in cultured skin cells to figure out whether Th1 or Th2 pathways
play a specific role in the pathogenesis of AA.
PMID- 25853542
TI - Predictors of drug resistance in tuberculosis patients in the Eastern Province,
Saudi Arabia.
AB - BACKGROUND: Management of patients with drug-resistant tuberculosis is highly
complicated because of the longer treatment time, lesser effectiveness of second
line antituberculosis drugs, more side-effects, and a significant financial
burden on tuberculosis control programs. This study aimed to identify predictors
of drug-resistant tuberculosis. MATERIALS AND METHODS: It was a case-control
record study conducted in an antituberculosis center in a government hospital in
the Eastern Province of Saudi Arabia. Cases were pulmonary tuberculosis patients
with antituberculosis drug resistance (n=80), and controls were pulmonary
tuberculosis patients without drug resistance (n=101). Data were collected from
patients' records during the period from January 2008 to February 2013. RESULTS:
Male sex [odds ratio (OR)=5.764; 95% confidence interval (CI) 2.024-16.421],
smoking (OR=4.605; 95% CI 1.864-11.378), and positive Acid Fast Bacilli smear on
admission (OR=40.149; 95% CI 9.010-178.914) were the risk factors for developing
drug resistance (P<0.05 for each) in the sample. CONCLUSION AND RECOMMENDATIONS:
Positive AFB smear on admission, male sex, and smoking are risk factors for
developing drug-resistant TB. These predictors should be used to formulate a
health policy to monitor tuberculosis patients so as to prevent drug resistance.
PMID- 25853543
TI - Health-promoting lifestyle behaviors among nurses in private hospitals in Al
Khobar, Saudi Arabia.
AB - BACKGROUND: An individual's lifestyle influences health, and health-promoting
behaviors and a healthy lifestyle are crucial means to maintain health. Nurses
play a significant role as models in health-promoting activities. OBJECTIVE: The
aim of this study was to describe the current health-promoting lifestyle of
nurses in private hospitals and investigate possible associations between health
behaviors and demographic characteristics. PARTICIPANTS AND METHODS: This was a
cross-sectional study. A total of 420 nurses were assessed using the Health
Promotion Lifestyle Profile (HPLP-II) scale as a self-administered questionnaire.
RESULTS: The mean age of about 78% women and 22% men was 33.12+/-8.52 years. Most
of them (98%) were non-Saudi, and 50% had a diploma; 38% had 5-10 years of
experience, 50% were married, 49% had children, and 64% had a monthly income of
less than 3000 Saudi Riyal. 'Spiritual growth' showed the highest mean score and
'physical activity' showed the lowest mean score. Significant differences in
nurses' health-promoting lifestyle behaviors and significant correlations were
found between the HPLP-II and demographic variables. CONCLUSION: Nurses' display
of health responsibility, nutrition, interpersonal relations, and stress
management behaviors was moderate. Although their physical activity was low,
their spiritual growth was high. For older, married, and those nurses whose
monthly income was more than 3000 Saudi Riyal, the nutrition score was higher.
Age, marital, and economic status were associated significantly with nutritional
health behavior. RECOMMENDATION: Development and training programs should be
performed to raise awareness of the importance of health education and health
promotion, and the necessary facilities should be provided at the work place to
encourage healthy behavior.
PMID- 25853544
TI - Prevalence of cardiovascular disease risk factors among Egyptian and Saudi
medical students: a comparative study.
AB - BACKGROUND: Results from recent reports suggest that the mortality and the
morbidity from coronary heart disease (CHD) is leveling, especially in younger
adults. Studies conducted in both Saudi Arabia and Egypt, aiming at the
estimation of the prevalence of cardiovascular risk factors among the young
population, demonstrated a high prevalence of risk factors. OBJECTIVE: The aim of
this study was to compare the prevalence of cardiovascular risk factors among
medical students aged 18-25 years in two Middle East countries (Egypt and Saudi
Arabia). PARTICIPANTS AND METHODS: This was a cross-sectional comparative study
involving a sample of 360 medical students of both sexes randomly selected from
students enrolled into two medical colleges in Saudi Arabia and Egypt. RESULTS:
The prevalence of risk factors for cardiovascular disease was relatively high
among both Saudi and Egyptian medical students, particularly a sedentary life
style, obesity, and abdominal obesity. Smoking was practiced by 29.7% of both
populations. A significantly higher prevalence of obesity and a reported family
history of premature CHD were observed among the Saudi students and a
significantly higher prevalence of hypertension was found among male Egyptian
students as compared with male Saudi students. A relatively high proportion of
both populations (23.9% of Saudi students and 16.7% of the Egyptian students) was
at an increased risk of developing fatal cardiovascular disease within 10 years.
CONCLUSION: Apart from the higher prevalence of obesity and reported family
history of premature CHD among the Saudi students and the significantly higher
prevalence of hypertension among the Egyptian students, there was no
statistically significant difference between the risk profiles of both
populations. Participatory behavior change programs in medical schools for the
adoption of healthy lifestyles, particularly involvement in regular physical
activity and smoking cessation are highly recommended.
PMID- 25853545
TI - Mild ammonium stress increases chlorophyll content in Arabidopsis thaliana.
AB - Nitrate (NO3(-)) and ammonium (NH4(+)) are the main forms of nitrogen available
in the soil for plants. Excessive NH4(+) accumulation in tissues is toxic for
plants and exclusive NH4(+)-based nutrition enhances this effect. Ammonium
toxicity syndrome commonly includes growth impairment, ion imbalance and
chlorosis among others. In this work, we observed high intraspecific variability
in chlorophyll content in 47 Arabidopsis thaliana natural accessions grown under
1 mM NH4(+) or 1 mM NO3(-) as N-source. Interestingly, chlorophyll content
increased in every accession upon ammonium nutrition. Moreover, this increase was
independent of ammonium tolerance capacity. Thus, chlorosis seems to be an
exclusive effect of severe ammonium toxicity while mild ammonium stress induces
chlorophyll accumulation.
PMID- 25853546
TI - Vertically-aligned carbon nanotubes on aluminum as a light-weight positive
electrode for lithium-polysulfide batteries.
AB - A light-weight, high specific surface current collector made of vertically
aligned carbon nanotubes grown on an aluminum substrate was fabricated and
studied as a positive electrode in a semi-liquid lithium/polysulfide battery.
This simple system delivered stable capacities over 1000 mA h gS(-1) and 2 mA h
cm(-2) with almost no capacity loss over 50 cycles.
PMID- 25853547
TI - Orientated Guidance of Peripheral Nerve Regeneration Using Conduits with a
Microtube Array Sheet (MTAS).
AB - Material surface topography has been shown to affect the biological behavior of
cells in vitro; however, the in vivo effect on peripheral nerve regeneration has
not been explored. Here, we studied the potential of a microtube array sheet
(MTAS) with a unique longitudinal surface topography to promote peripheral nerve
regeneration efficiency, both in vivo and in vitro. Schwann cells, spinal cord
motor neurons, and dorsal root ganglion neurons were seeded on the MTAS to study
the effect of the construct on the biological properties and behaviors of neural
cells. The MTAS guided the oriented migration of Schwann cells without affecting
other critical biological properties, such as proliferation and neurotrophin
expression. In addition, the MTAS guided the directed extension of neurites from
both types of neurons. Next, we tested the capability of the MTAS to facilitate
peripheral nerve regeneration by bridging a 10 mm sciatic nerve defect in rats
with a nerve conduit equipped with an MTAS lining. The MTAS significantly
promoted peripheral nerve regeneration, as suggested by the greater fiber caliber
in the midconduit and the greater abundance of fibers in nerve segment distal to
the conduit. Moreover, scanning electron microscopy (SEM) analysis suggested the
orientated guidance of nerve regeneration by the MTAS, as indicated by the
smaller eccentricity of the nerve fibers and the concordant arrangement of the
collagen fiber in both the fibers and the matrix in the MTAS group. Our results
collectively suggest that the conduits with the MTAS developed in this study have
significant potential for facilitating peripheral nerve regeneration by modifying
critical biological behaviors and guiding orientated nerve growth.
PMID- 25853548
TI - Aptamer-conjugated polymeric nanoparticles for the detection of cancer cells
through "turn-on" retro-self-quenched fluorescence.
AB - We have developed a simple, sensitive, and rapid fluorescence assay for the
detection of cancer cells, based on "turn-on" retro-self-quenched fluorescence
inside the cells. 1,3-Phenylenediamine resin (DAR) nanoparticles (NPs) containing
rhodamine 6G (R6G) are conjugated with aptamer (apt) sgc8c to prepare sgc8c
R6GDAR NPs, while that containing rhodamine 101 (R101) are conjugated with TD05
for the preparation of TD05-R101DAR NPs. The sgc8c-R6GDAR and TD05-R101DAR NPs
separately recognize CCRF-CEM and Ramos cells. The fluorescence intensities of
the two apt-DAR NPs are both weak due to self-quenching, but they increase inside
the cells as a result of release of the fluorophores from the apt-DAR NPs. The
apt-DAR NPs' structure becomes less compact at low pH value, leading to the
release of the fluorophores. The sgc8c-R6GDAR and TD05-R101DAR NPs allow
detection of as low as 44 CCRF-CEM cells and 79 Ramos cells mL(-1), respectively,
using a commercial reader within 10 min. Practicality of the two probes have been
validated by the quantitation and identification of CCRF-CEM and Ramos cells
spiked in blood samples through conventional fluorescence and flow cytometry
analysis, with advantages of sensitivity, selectivity, and rapidity.
PMID- 25853549
TI - Detection of mitochondrial COII DNA sequences in ant guts as a method for
assessing termite predation by ants.
AB - Termites and ants contribute more to animal biomass in tropical rain forests than
any other single group and perform vital ecosystem functions. Although ants prey
on termites, at the community level the linkage between these groups is poorly
understood. Thus, assessing the distribution and specificity of ant termitophagy
is of considerable interest. We describe an approach for quantifying ant-termite
food webs by sequencing termite DNA (cytochrome c oxidase subunit II, COII) from
ant guts and apply this to a soil-dwelling ant community from tropical rain
forest in Gabon. We extracted DNA from 215 ants from 15 species. Of these, 17.2 %
of individuals had termite DNA in their guts, with BLAST analysis confirming the
identity of 34.1 % of these termites to family level or better. Although ant
species varied in detection of termite DNA, ranging from 63 % (5/7; Camponotus
sp. 1) to 0 % (0/7; Ponera sp. 1), there was no evidence (with small sample
sizes) for heterogeneity in termite consumption across ant taxa, and no evidence
for species-specific ant-termite predation. In all three ant species with
identifiable termite DNA in multiple individuals, multiple termite species were
represented. Furthermore, the two termite species that were detected on multiple
occasions in ant guts were in both cases found in multiple ant species,
suggesting that ant-termite food webs are not strongly compartmentalised.
However, two ant species were found to consume only Anoplotermes-group termites,
indicating possible predatory specialisation at a higher taxonomic level. Using a
laboratory feeding test, we were able to detect termite COII sequences in ant
guts up to 2 h after feeding, indicating that our method only detects recent
feeding events. Our data provide tentative support for the hypothesis that
unspecialised termite predation by ants is widespread and highlight the use of
molecular approaches for future studies of ant-termite food webs.
PMID- 25853550
TI - Characterization of the immunophenotypes and antigenomes of colorectal cancers
reveals distinct tumor escape mechanisms and novel targets for immunotherapy.
AB - BACKGROUND: While large-scale cancer genomic projects are comprehensively
characterizing the mutational spectrum of various cancers, so far little
attention has been devoted to either define the antigenicity of these mutations
or to characterize the immune responses they elicit. Here we present a strategy
to characterize the immunophenotypes and the antigen-ome of human colorectal
cancer. RESULTS: We apply our strategy to a large colorectal cancer cohort (n =
598) and show that subpopulations of tumor-infiltrating lymphocytes are
associated with distinct molecular phenotypes. The characterization of the
antigenome shows that a large number of cancer-germline antigens are expressed in
all patients. In contrast, neo-antigens are rarely shared between patients,
indicating that cancer vaccination requires individualized strategy. Analysis of
the genetic basis of the tumors reveals distinct tumor escape mechanisms for the
patient subgroups. Hypermutated tumors are depleted of immunosuppressive cells
and show upregulation of immunoinhibitory molecules. Non-hypermutated tumors are
enriched with immunosuppressive cells, and the expression of immunoinhibitors and
MHC molecules is downregulated. Reconstruction of the interaction network of
tumor-infiltrating lymphocytes and immunomodulatory molecules followed by a
validation with 11 independent cohorts (n = 1,945) identifies BCMA as a novel
druggable target. Finally, linear regression modeling identifies major
determinants of tumor immunogenicity, which include well-characterized modulators
as well as a novel candidate, CCR8, which is then tested in an orthologous
immunodeficient mouse model. CONCLUSIONS: The immunophenotypes of the tumors and
the cancer antigenome remain widely unexplored, and our findings represent a step
toward the development of personalized cancer immunotherapies.
PMID- 25853552
TI - Increased isolation frequency of toxigenic Vibrio cholerae O1 from environmental
monitoring sites in Haiti.
AB - Since the identification of the first cholera case in 2010, the disease has
spread in epidemic form throughout the island nation of Haiti; as of 2014, about
700,000 cholera cases have been reported, with over 8,000 deaths. While case
numbers have declined, the more fundamental question of whether the causative
bacterium, Vibrio cholerae has established an environmental reservoir in the
surface waters of Haiti remains to be elucidated. In a previous study conducted
between April 2012 and March 2013, we reported the isolation of toxigenic V.
cholerae O1 from surface waters in the Ouest Department. After a second year of
surveillance (April 2013 to March 2014) using identical methodology, we observed
a more than five-fold increase in the number of water samples containing
culturable V. cholerae O1 compared to the previous year (1.7% vs 8.6%), with
double the number of sites having at least one positive sample (58% vs 20%). Both
seasonal water temperatures and precipitation were significantly related to the
frequency of isolation. Our data suggest that toxigenic V. cholerae O1 are
becoming more common in surface waters in Haiti; while the basis for this
increase is uncertain, our findings raise concerns that environmental reservoirs
are being established.
PMID- 25853553
TI - Identification of novel adipokines in the joint. Differential expression in
healthy and osteoarthritis tissues.
AB - OBJECTIVES: Emerging data suggest that several metabolic factors, released mainly
by white adipose tissue (WAT) and joint tissues, and collectively named
adipokines, might have a role in the pathophysiology of OA. Recently, novel
adipokines such as SERPINE2, WISP2, GPNMB and ITIH5 have been identified in WAT.
The main goal of this study was to analyse the expression of these novel
adipokines in synovium, infrapatellar fat pad and chondrocytes and to compare the
expression of these molecules in healthy and OA tissues. METHODS: Synovial
tissues, infrapatellar fat pad and chondrocytes were obtained from 36 OA patients
(age 52-85; mean BMI 28.9) who underwent total knee replacement surgery. Healthy
synovial tissues and infrapatellar fat pad were obtained from 15 traumatic knee
patients (age 23-53; mean BMI 23.5). mRNA and protein expression were determined
by qRT-PCR and western blot analysis respectively. RESULTS: All the novel
adipokines, matter of our study, are expressed in OA synovium, infrapatellar fat
pad and chondrocytes. Moreover, we detected a differential expression of SERPINE2
and ITIH5 in OA synovial tissues as compared to healthy samples. Finally, we also
observed an increased expression of WISP2 in OA infrapatellar fat pad in
comparison to healthy controls. CONCLUSIONS: In this study we demonstrated for
the first time the expression of four novel adipokines in different joint tissues
and how these molecules are differentially expressed in healthy and OA joint
tissues.
PMID- 25853555
TI - Density of Trap States and Auger-mediated Electron Trapping in CdTe Quantum-Dot
Solids.
AB - Charge trapping is an ubiquitous process in colloidal quantum-dot solids and a
major limitation to the efficiency of quantum dot based devices such as solar
cells, LEDs, and thermoelectrics. Although empirical approaches led to a
reduction of trapping and thereby efficiency enhancements, the exact chemical
nature of the trapping mechanism remains largely unidentified. In this study, we
determine the density of trap states in CdTe quantum-dot solids both
experimentally, using a combination of electrochemical control of the Fermi level
with ultrafast transient absorption and time-resolved photoluminescence
spectroscopy, and theoretically, via density functional theory calculations. We
find a high density of very efficient electron traps centered ~0.42 eV above the
valence band. Electrochemical filling of these traps increases the electron
lifetime and the photoluminescence quantum yield by more than an order of
magnitude. The trapping rate constant for holes is an order of magnitude lower
that for electrons. These observations can be explained by Auger-mediated
electron trapping. From density functional theory calculations we infer that the
traps are formed by dicoordinated Te atoms at the quantum dot surface. The
combination of our unique experimental determination of the density of trap
states with the theoretical modeling of the quantum dot surface allows us to
identify the trapping mechanism and chemical reaction at play during charge
trapping in these quantum dots.
PMID- 25853557
TI - 3D bite modeling and feeding mechanics of the largest living amphibian, the
Chinese giant salamander Andrias davidianus (Amphibia:Urodela).
AB - Biting is an integral feature of the feeding mechanism for aquatic and
terrestrial salamanders to capture, fix or immobilize elusive or struggling prey.
However, little information is available on how it works and the functional
implications of this biting system in amphibians although such approaches might
be essential to understand feeding systems performed by early tetrapods. Herein,
the skull biomechanics of the Chinese giant salamander, Andrias davidianus is
investigated using 3D finite element analysis. The results reveal that the prey
contact position is crucial for the structural performance of the skull, which is
probably related to the lack of a bony bridge between the posterior end of the
maxilla and the anterior quadrato-squamosal region. Giant salamanders perform
asymmetrical strikes. These strikes are unusual and specialized behavior but
might indeed be beneficial in such sit-and-wait or ambush-predators to capture
laterally approaching prey. However, once captured by an asymmetrical strike,
large, elusive and struggling prey have to be brought to the anterior jaw region
to be subdued by a strong bite. Given their basal position within extant
salamanders and their "conservative" morphology, cryptobranchids may be useful
models to reconstruct the feeding ecology and biomechanics of different members
of early tetrapods and amphibians, with similar osteological and myological
constraints.
PMID- 25853556
TI - Combined biomarker analysis for risk of acute kidney injury in patients with ST
segment elevation myocardial infarction.
AB - BACKGROUND: Acute kidney injury (AKI) complicating ST-segment elevation
myocardial infarction (STEMI) increases subsequent morbidity and mortality. We
combined the biomarkers of heart failure (HF; B-type natriuretic peptide [BNP]
and soluble ST2 [sST2]) and renal injury (NGAL [neutrophil gelatinase-associated
lipocalin] and cystatin C) in predicting the development of AKI in patients with
STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS AND
RESULTS: From March 2010 to September 2013, 189 STEMI patients were sequentially
enrolled and serum samples were collected at presentation for BNP, sST2, NGAL and
cystatin C analysis. 37 patients (19.6%) developed AKI of varying severity within
48 hours of presentation. Univariate analysis showed age, Killip class >=2,
hypertension, white blood cell counts, hemoglobin, estimated glomerular
filtration rate, blood urea nitrogen, creatinine, and all the four biomarkers
were predictive of AKI. Serum levels of the biomarkers were correlated with risk
of AKI and the Acute Kidney Injury Network (AKIN) stage and all significantly
discriminated AKI (area under the receiver operating characteristic [ROC] curve:
BNP: 0.86, sST2: 0.74, NGAL: 0.75, cystatin C: 0.73; all P < 0.05). Elevation of
>=2 of the biomarkers higher than the cutoff values derived from the ROC analysis
improved AKI risk stratification, regardless of the creatine level (creatinine <
1.24 mg/dL: odds ratio [OR] 11.25, 95% confidence interval [CI] 1.63-77.92, P =
0.014; creatinine >= 1.24: OR 15.0, 95% CI 1.23-183.6, P = 0.034). CONCLUSIONS:
In this study of STEMI patients undergoing primary PCI, the biomarkers of heart
failure (BNP and sST2) and renal injury (NGAL and cystatin C) at presentation
were predictive of AKI. High serum levels of the biomarkers were associated with
an elevated risk and more advanced stage of AKI. Regardless of the creatinine
level, elevation of >=2 of the biomarkers higher than the cutoff values indicated
a further rise in AKI risk. Combined biomarker approach may assist in risk
stratification of AKI in patients with STEMI.
PMID- 25853558
TI - Bacteria isolated from bats inhibit the growth of Pseudogymnoascus destructans,
the causative agent of white-nose syndrome.
AB - Emerging infectious diseases are a key threat to wildlife. Several fungal skin
pathogens have recently emerged and caused widespread mortality in several
vertebrate groups, including amphibians, bats, rattlesnakes and humans. White
nose syndrome, caused by the fungal skin pathogen Pseudogymnoascus destructans,
threatens several hibernating bat species with extinction and there are few
effective treatment strategies. The skin microbiome is increasingly understood to
play a large role in determining disease outcome. We isolated bacteria from the
skin of four bat species, and co-cultured these isolates with P. destructans to
identify bacteria that might inhibit or kill P. destructans. We then conducted
two reciprocal challenge experiments in vitro with six bacterial isolates (all in
the genus Pseudomonas) to quantify the effect of these bacteria on the growth of
P. destructans. All six Pseudomonas isolates significantly inhibited growth of P.
destructans compared to non-inhibitory control bacteria, and two isolates
performed significantly better than others in suppressing P. destructans growth
for at least 35 days. In both challenge experiments, the extent of suppression of
P. destructans growth was dependent on the initial concentration of P.
destructans and the initial concentration of the bacterial isolate. These results
show that bacteria found naturally occurring on bats can inhibit the growth of P.
destructans in vitro and should be studied further as a possible probiotic to
protect bats from white-nose syndrome. In addition, the presence of these
bacteria may influence disease outcomes among individuals, populations, and
species.
PMID- 25853559
TI - A coding variant in TMC8 (EVER2) is associated with high risk HPV infection and
head and neck cancer risk.
AB - HPV infection is a causal agent in many epithelial cancers, yet our understanding
of genetic susceptibility to HPV infection and resultant cancer risk is limited.
Epidermodysplasia Verruciformis is a rare condition of extreme susceptibility to
cutaneous HPV infection primarily attributable to mutations in TMC6 and TMC8.
Genetic variation in the TMC6/TMC8 region has been linked to beta-type HPV
infection and squamous cell carcinoma of the skin, cervical cancer, HPV
persistence and progression to cervical cancer. Here, we have tested the
hypothesis that the common TMC8 SNP rs7208422 is associated with high-risk HPV
infection and risk of head and neck squamous cell carcinoma (HNSCC).
Seropositivity to the HPV L1 protein (HPV16, 18, 11, 31, 33, 35, 45, 52, 58) was
measured in 514 cases and 452 population-based controls. Genotype was
significantly associated with seropositivity to HPV18 L1 (OR TT vs AA = 0.48, 95%
CI = 0.22-0.99) and borderline significantly associated with HPV16 L1 (OR TT vs
AA = 0.58, 95% CI = 0.22-1.17). There was a consistent inverse association
between TMC8 genotype and infection with other HPV types, including statistically
significant associations for HPV31 and HPV52. Consistent with these results, the
variant T genotype was associated with a reduced risk of HNSCC (ORAT: 0.63, 95%
CI 0.45-0.89, ORTT: 0.54, 95% CI 0.36-0.81), even among subjects seronegative for
all HPV types (ORAT: 0.71, 95% CI 0.45-1.11, ORTT: 0.54, 95% CI 0.31-0.93). Our
data indicate that common genetic variation in TMC8 is associated with high-risk
HPV infection and HNSCC etiology.
PMID- 25853560
TI - A DIseAse MOdule Detection (DIAMOnD) algorithm derived from a systematic analysis
of connectivity patterns of disease proteins in the human interactome.
AB - The observation that disease associated proteins often interact with each other
has fueled the development of network-based approaches to elucidate the molecular
mechanisms of human disease. Such approaches build on the assumption that protein
interaction networks can be viewed as maps in which diseases can be identified
with localized perturbation within a certain neighborhood. The identification of
these neighborhoods, or disease modules, is therefore a prerequisite of a
detailed investigation of a particular pathophenotype. While numerous heuristic
methods exist that successfully pinpoint disease associated modules, the basic
underlying connectivity patterns remain largely unexplored. In this work we aim
to fill this gap by analyzing the network properties of a comprehensive corpus of
70 complex diseases. We find that disease associated proteins do not reside
within locally dense communities and instead identify connectivity significance
as the most predictive quantity. This quantity inspires the design of a novel
Disease Module Detection (DIAMOnD) algorithm to identify the full disease module
around a set of known disease proteins. We study the performance of the algorithm
using well-controlled synthetic data and systematically validate the identified
neighborhoods for a large corpus of diseases.
PMID- 25853561
TI - A 9-year retrospective evaluation of 102 pressure ulcer reconstructions.
AB - OBJECTIVE: Several pressure ulcer (PU) risk factors including paralysis and age
greater than 70 have been identified, while others such as nutrition are debated.
The object of this study is to identify perioperative risk factors that may
predict improved outcomes and reduced complications in primary and recurrent PU
reconstructions. METHOD: A retrospective chart review of patients treated
surgically for PUs from 2004 to 2013 at the University of Toledo Medical Center,
Toledo, Ohio, US, was completed. Data collected included ulcer and medical
history, as well as risk factors, complications and postoperative outcome. Data
were statistically analysed for perioperative variances between primary and
recurrent ulcers and closure status. RESULTS: A total of 49 patients with 102
reconstructions were reviewed. Spinal cord injured patients accounted for 90%
receiving flap coverage of ulcers. Numerous differences between primary and
recurrent ulcers were identified, including ulcer location, patient nutritional
status, wound infection, postoperative course and recurrence. Multivariate
analysis revealed a flap reconstruction prediction model using creatinine,
haematocrit, haemoglobin, and prealbumin that is able to successfully predict
closure outcome in 83.6% of cases. CONCLUSION: Many factors play a role in the
development, course and treatment of PUs. It is vital to understand the role of
patient risk factors in the development of PUs, to direct subsequent management
and reconstruction, and to prevent future recurrences. DECLARATION OF INTEREST:
The authors have no conflicts of interest to disclose.
PMID- 25853563
TI - Clinical evaluation of a silver-impregnated foam dressing in paediatric partial
thickness burns.
AB - OBJECTIVE: Mepilex Ag, a silver-impregnated foam dressing, was introduced to our
institution in 2007 and our outcomes in the treatment of paediatric burns were
observed to improve significantly. In order to confirm these observations, we
wanted to evaluate the results of using the silver-impregnated foam dressing in
partial-thickness paediatric burns. METHOD: In this retrospective study, the St.
Christopher's Hospital burn registry was used to identify subjects, who were
otherwise in excellent health at baseline, over an18-month period. Outcomes
included length of stay, intravenous narcotic use, and time to healing. No direct
comparative studies were performed. This was followed by a non-comparative
prospective study involving 22 paediatric patients, aged 1-4 years, with partial
thickness burns. This was a sub-study of a larger randomised controlled trial
involving adults with partial-thickness burns, comparing the silver-impregnated
foam dressing with Silvadene. RESULTS: In the retrospective part of the study,
the silver-impregnated foam dressing was used successfully for the treatment of
partial-thickness paediatric burns, with few complications and infections,
allowing a shorter hospital stay, fewer dressings, and less pain medication than
for historical controls. In the non-comparative prospective study, of 22
paediatric patients 50% healed completely within 1 week of treatment. The mean
length of stay was 3.77 days and the mean number of dressings used was 1.64.
Although narcotic usage was not assessed, patient surveys showed stinging or
burning to be recorded as 'never' in 13 patients, 'rarely' in 8 patients, and
'sometimes' in 1 patient. CONCLUSION: The silver-impregnated foam dressing is
effective and safe for use in partial-thickness paediatric burns, eliminating the
need for daily dressings. DECLARATION OF INTEREST: The study was supported by an
educational grant from Molnlycke Health Care.
PMID- 25853564
TI - Functional characterization of the spf/ash splicing variation in OTC deficiency
of mice and man.
AB - The spf/ash mouse model of ornithine transcarbamylase (OTC) deficiency, a severe
urea cycle disorder, is caused by a mutation (c.386G>A; p.R129H) in the last
nucleotide of exon 4 of the Otc gene, affecting the 5' splice site and resulting
in partial use of a cryptic splice site 48 bp into the adjacent intron. The
equivalent nucleotide change and predicted amino acid change is found in OTC
deficient patients. Here we have used liver tissue and minigene assays to dissect
the transcriptional profile resulting from the "spf/ash" mutation in mice and
man. For the mutant mouse, we confirmed liver transcripts corresponding to
partial intron 4 retention by the use of the c.386+48 cryptic site and to
normally spliced transcripts, with exon 4 always containing the c.386G>A
(p.R129H) variant. In contrast, the OTC patient exhibited exon 4 skipping or
c.386G>A (p.R129H)-variant exon 4 retention by using the natural or a cryptic
splice site at nucleotide position c.386+4. The corresponding OTC tissue enzyme
activities were between 3-6% of normal control in mouse and human liver. The use
of the cryptic splice sites was reproduced in minigenes carrying murine or human
mutant sequences. Some normally spliced transcripts could be detected in
minigenes in both cases. Antisense oligonucleotides designed to block the murine
cryptic +48 site were used in minigenes in an attempt to redirect splicing to the
natural site. The results highlight the relevance of in depth investigations of
the molecular mechanisms of splicing mutations and potential therapeutic
approaches. Notably, they emphasize the fact that findings in animal models may
not be applicable for human patients due to the different genomic context of the
mutations.
PMID- 25853565
TI - Regiospecific Hetero-Assembly of DNA-Functionalized Plasmonic Upconversion
Superstructures.
AB - We report a novel strategy for regiospecific hetero-assembly of DNA-modified gold
nanoparticles (DNA-AuNPs) onto upconversion nanoparticles (UCNPs) into hybrid lab
on-a-particle systems. The DNA-AuNPs have been assembled onto the hexagonal plate
like UCNPs with well-regulated stoichiometry and controlled organization onto the
different facets of UCNP, forming various addressable superstructures. The fine
tuning of stoichiometry and organization is realized by biorecognition
specificity of DNA toward specific crystal facets of UCNPs. Such a hetero
assembled DNA-AuNP/UCNP system maintains both plasmonic resonance of AuNPs and
fluorescent properties of UCNPs, allowing targeted dual-modality imaging of
cancer cells using an aptamer.
PMID- 25853567
TI - Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function
Sigma Factor in Stress Response.
AB - Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) sigma
factors. To begin to investigate the regulatory network of one of these ECF sigma
factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by
tandem mass spectrometry from cultures episomally expressing the ECF
sigma(RPA4225) (ecfT) versus a WT control. Among the proteins with the greatest
increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein,
and several regulatory proteins. Alignment of the cognate promoter regions
driving expression of several upregulated proteins suggested a conserved binding
motif in the -35 and -10 regions with the consensus sequence GGAAC-18N-TT.
Additionally, the putative anti-sigma factor RPA4224, whose gene is contained in
the same predicted operon as RPA4225, was identified as interacting directly with
the predicted response regulator RPA4223 by mass spectrometry of affinity
isolated protein complexes. Furthermore, another gene (RPA4226) coding for a
protein that contains a cytoplasmic histidine kinase domain is located
immediately upstream of RPA4225. The genomic organization of orthologs for these
four genes is conserved in several other strains of R. palustris as well as in
closely related alpha-Proteobacteria. Taken together, these data suggest that ECF
sigma(RPA4225) and the three additional genes make up a sigma factor mimicry
system in R. palustris.
PMID- 25853566
TI - Salinity regulation of the interaction of halovirus SNJ1 with its host and
alteration of the halovirus replication strategy to adapt to the variable
ecosystem.
AB - Halovirus is a major force that affects the evolution of extreme halophiles and
the biogeochemistry of hypersaline environments. However, until now, the
systematic studies on the halovirus ecology and the effects of salt concentration
on virus-host systems are lacking. To provide more valuable information for
understanding ecological strategies of a virus-host system in the hypersaline
ecosystem, we studied the interaction between halovirus SNJ1 and its host
Natrinema sp.J7-2 under various NaCl concentrations. We found that the adsorption
rate and lytic rate increased with salt concentration, demonstrating that a
higher salt concentration promoted viral adsorption and proliferation. Contrary
to the lytic rate, the lysogenic rate decreased as the salt concentration
increased. Our results also demonstrated that cells incubated at a high salt
concentration prior to infection increased the ability of the virus to adsorb and
lyse its host cells; therefore, the physiological status of host cells also
affected the virus-host interaction. In conclusion, SNJ1 acted as a predator,
lysing host cells and releasing progeny viruses in hypersaline environments; in
low salt environments, viruses lysogenized host cells to escape the damage from
low salinity.
PMID- 25853569
TI - An in vitro study comparing two dose regimes of fresh frozen plasma on
conventional and thromboelastographic tests of coagulation after major hepatic
resection.
AB - BACKGROUND: After hepatic resection, post-operative increases in international
normalised ratio (INR) are frequent, but rarely associated with bleeding
complication. Coagulation as assessed by thrombin generation may be normal,
despite the increased INR. This study tests the hypothesis that viscoelastic
tests (VET) of coagulation remain normal, despite mild elevations in INR,
examines the efficacy of fresh frozen plasma (FFP) in reversing prolongation of
INR in such patients and determines the effect of FFP on VET. METHODS: A
prospective cohort study of 47 patients undergoing major hepatectomy. In vitro
spiking with FFP (7.5 and 15 mL kg(-1)) was carried out if post-operative day 2
(POD2) INR levels were >=1.5. Thromboelastography (TEG(r)) and INR were measured
before and after FFP spiking. RESULTS: Blood from patients with an INR >= 1.5 on
POD2 was spiked with FFP. There was a significant reduction in the INR from 1.94
[standard deviation (SD): 0.59] to 1.46 (SD: 0.27, P = 0.005) and 1.36 (SD: 0.18,
P = 0.0007) with FFP 7.5 or 15 mL kg(-1), respectively. At baseline, the TEG R
time [6.17 min (NR, 9-27 min)] and maximum amplitude (MA) [66.9 mm (NR, 44-64
mm)] were hypercoagulable, and remained so on POD2 for the R-time (6.7 min), but
fell to within the normal range for the MA (54.0 mm). FFP spiking had no
significant effect on TEG variables. CONCLUSIONS: Despite the rise in INR after
hepatectomy, VET do not show evidence of hypocoagulability. In vitro addition of
FFP had no significant effect on TEG parameters. Clinical use of FFP in this
situation is questionable.
PMID- 25853570
TI - Response of moose hunters to predation following wolf return in Sweden.
AB - BACKGROUND: Predation and hunter harvest constitute the main mortality factors
affecting the size and dynamics of many exploited populations. The re
colonization by wolves (Canis lupus) of the Scandinavian Peninsula may therefore
substantially reduce hunter harvest of moose (Alces alces), the main prey of
wolves. METHODOLOGY/PRINCIPAL FINDINGS: We examined possible effects of wolf
presence on hunter harvest in areas where we had data before and after wolf
establishment (n = 25), and in additional areas that had been continuously
exposed to wolf predation during at least ten years (n = 43). There was a general
reduction in the total number of moose harvested (n = 31,827) during the ten year
study period in all areas irrespective of presence of wolves or not. However, the
reduction in hunter harvest was stronger within wolf territories compared to
control areas without wolves. The reduction in harvest was larger in small (500
800 km2) compared to large (1,200-1,800 km2) wolf territories. In areas with
newly established wolf territories moose management appeared to be adaptive with
regard to both managers (hunting quotas) and to hunters (actual harvest). In
these areas an instant reduction in moose harvest over-compensated the estimated
number of moose killed annually by wolves and the composition of the hunted
animals changed towards a lower proportion of adult females.
CONCLUSIONS/SIGNIFICANCE: We show that the re-colonization of wolves may result
in an almost instant functional response by another large predator-humans-that
reduced the potential for a direct numerical effect on the density of wolves'
main prey, the moose. Because most of the worlds' habitat that will be available
for future colonization by large predators are likely to be strongly influenced
by humans, human behavioural responses may constitute a key trait that govern the
impact of large predators on their prey.
PMID- 25853568
TI - FRESCo: finding regions of excess synonymous constraint in diverse viruses.
AB - BACKGROUND: The increasing availability of sequence data for many viruses
provides power to detect regions under unusual evolutionary constraint at a high
resolution. One approach leverages the synonymous substitution rate as a
signature to pinpoint genic regions encoding overlapping or embedded functional
elements. Protein-coding regions in viral genomes often contain overlapping RNA
structural elements, reading frames, regulatory elements, microRNAs, and
packaging signals. Synonymous substitutions in these regions would be selectively
disfavored and thus these regions are characterized by excess synonymous
constraint. Codon choice can also modulate transcriptional efficiency,
translational accuracy, and protein folding. RESULTS: We developed a phylogenetic
codon model-based framework, FRESCo, designed to find regions of excess
synonymous constraint in short, deep alignments, such as individual viral genes
across many sequenced isolates. We demonstrated the high specificity of our
approach on simulated data and applied our framework to the protein-coding
regions of approximately 30 distinct species of viruses with diverse genome
architectures. CONCLUSIONS: FRESCo recovers known multifunctional regions in well
characterized viruses such as hepatitis B virus, poliovirus, and West Nile virus,
often at a single-codon resolution, and predicts many novel functional elements
overlapping viral genes, including in Lassa and Ebola viruses. In a number of
viruses, the synonymously constrained regions that we identified also display
conserved, stable predicted RNA structures, including putative novel elements in
multiple viral species.
PMID- 25853571
TI - Socioeconomic inequalities in mortality and repeated measurement of explanatory
risk factors in a 25 years follow-up.
AB - BACKGROUND: Socioeconomic inequalities in mortality can be explained by different
groups of risk factors. However, little is known whether repeated measurement of
risk factors can provide better explanation of socioeconomic inequalities in
health. Our study examines the extent to which relative educational and income
inequalities in mortality might be explained by explanatory risk factors
(behavioral, psychosocial, biomedical risk factors and employment) measured at
two points in time, as compared to one measurement at baseline. METHODS AND
FINDINGS: From the Norwegian total county population-based HUNT Study (years 1984
86 and 1995-1997, respectively) 61 513 men and women aged 25-80 (82.5% of all
enrolled) were followed-up for mortality in 25 years until 2009, employing a
discrete time survival analysis. Socioeconomic inequalities in mortality were
observed. As compared to their highest socioeconomic counterparts, the lowest
educated men had an OR (odds ratio) of 1.41 (95% CI 1.29-1.55) and for the lowest
income quartile OR = 1.59 (1.48-1.571), for women OR = 1.35 (1.17-1.55), and OR =
1.40 (1.28-1.52), respectively. Baseline explanatory variables attenuated the
association between education and income with mortality by 54% and 54% in men,
respectively, and by 69% and 18% in women. After entering time-varying variables,
this attainment increased to 63% and 59% in men, respectively, and to 25%
(income) in women, with no improvement in regard to education in women. Change in
biomedical factors and employment did not amend the explanation. CONCLUSIONS:
Addition of a second measurement for risk factors provided only a modest
improvement in explaining educational and income inequalities in mortality in
Norwegian men and women. Accounting for change in behavior provided the largest
improvement in explained inequalities in mortality for both men and women, as
compared to measurement at baseline. Psychosocial factors explained the largest
share of income inequalities in mortality for men, but repeated measurement of
these factors contributed only to modest improvement in explanation. Further
comparative research on the relative importance of explanatory pathways assessed
over time is needed.
PMID- 25853572
TI - Effects of maternal diet and exercise during pregnancy on glucose metabolism in
skeletal muscle and fat of weanling rats.
AB - Obesity during pregnancy contributes to the development of metabolic disorders in
offspring. Maternal exercise may limit gestational weight gain and ameliorate
these programming effects. We previously showed benefits of post-weaning
voluntary exercise in offspring from obese dams. Here we examined whether
voluntary exercise during pregnancy influences lipid and glucose homeostasis in
muscle and fat in offspring of both lean and obese dams. Female Sprague-Dawley
rats were fed chow (C) or high fat (F) diet for 6 weeks before mating. Half
underwent voluntary exercise (CE/FE) with a running wheel introduced 10 days
prior to mating and available until the dams delivered; others remained sedentary
(CS/FS). Male and female pups were killed at postnatal day (PND)19 and
retroperitoneal fat and gastrocnemius muscle were collected for gene expression.
Lean and obese dams achieved similar modest levels of exercise. At PND1, both
male and female pups from exercised lean dams were significantly lighter (CE
versus CS), with no effect in those from obese dams. At PND19, maternal obesity
significantly increased offspring body weight and adiposity, with no effect of
maternal exercise. Exercise significantly reduced insulin concentrations in males
(CE/FE versus CS/FS), with reduced glucose in male FE pups. In males, maternal
obesity significantly decreased muscle myogenic differentiation 1 (MYOD1) and
glucose transporter type 4 (GLUT4) mRNA expressions (FS vs CS); these were
normalized by exercise. Maternal exercise upregulated adipose GLUT4, interleukin
6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and peroxisome proliferator
activated receptor gamma coactivator 1 alpha (PGC1alpha) mRNA expression in
offspring of dams consuming chow. Modest voluntary exercise during pregnancy was
associated with lower birth weight in pups from lean dams. Maternal exercise
appeared to decrease the metabolic risk induced by maternal obesity, improving
insulin/glucose metabolism, with greater effects in male than female offspring.
PMID- 25853573
TI - Postoperative metamorphopsia in macula-off rhegmatogenous retinal detachment:
associations with visual function, vision related quality of life, and optical
coherence tomography findings.
AB - PURPOSE: To evaluate postoperative metamorphopsia in macula-off rhegmatogenous
retinal detachment (RRD) and its association with visual function, vision related
quality of life, and optical coherence tomography (OCT) findings. METHODS: 45
patients with primary macula-off RRD were included. At 12 months postoperatively,
data on metamorphopsia using sine amsler charts (SAC), best corrected visual
acuity (BCVA), letter contrast sensitivity, color vision (saturated and
desaturated color confusion indexes), critical print size, reading acuity, the 25
item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and
OCT, were obtained. RESULTS: Metamorphopsia was present in 39 patients (88.6%),
with most of them (n = 35, 77.8%) showing only mild metamorphopsia (SAC score =
1). Patients with metamorphopsia had significantly worse postoperative BCVA (p =
0.02), critical print size (p<0.0005), and reading acuity (p = 0.001) compared to
patients without metamorphopsia. Other visual function outcomes and NEI-VFQ-25
overall composite score were all also somewhat lower in patients with
metamorphopsia, but this did not reach statistical significance. No association
with OCT findings was present. CONCLUSION: The prevalence of postoperative
metamorphopsia in macula-off RRD patients is high, however, the degree of
metamorphopsia is relatively low. When metamorphopsia is present, visual
functions seem to be compromised, while vision related quality of life is only
mildly affected.
PMID- 25853574
TI - Timely Surgical Follow-up for Melanoma Among Medicare Beneficiaries.
PMID- 25853575
TI - Calibration of the gamma-H2AX DNA double strand break focus assay for internal
radiation exposure of blood lymphocytes.
AB - DNA double strand break (DSB) formation induced by ionizing radiation exposure is
indicated by the DSB biomarkers gamma-H2AX and 53BP1. Knowledge about DSB foci
formation in-vitro after internal irradiation of whole blood samples with
radionuclides in solution will help us to gain detailed insights about dose
response relationships in patients after molecular radiotherapy (MRT). Therefore,
we studied the induction of radiation-induced co-localizing gamma-H2AX and 53BP1
foci as surrogate markers for DSBs in-vitro, and correlated the obtained foci per
cell values with the in-vitro absorbed doses to the blood for the two most
frequently used radionuclides in MRT (I-131 and Lu-177). This approach led to an
in-vitro calibration curve. Overall, 55 blood samples of three healthy volunteers
were analyzed. For each experiment several vials containing a mixture of whole
blood and radioactive solutions with different concentrations of isotonic NaCl
diluted radionuclides with known activities were prepared. Leukocytes were
recovered by density centrifugation after incubation and constant blending for 1
h at 37 degrees C. After ethanol fixation they were subjected to two-color
immunofluorescence staining and the average frequencies of the co-localizing
gamma-H2AX and 53BP1 foci/nucleus were determined using a fluorescence microscope
equipped with a red/green double band pass filter. The exact activity was
determined in parallel in each blood sample by calibrated germanium detector
measurements. The absorbed dose rates to the blood per nuclear disintegrations
occurring in 1 ml of blood were calculated for both isotopes by a Monte Carlo
simulation. The measured blood doses in our samples ranged from 6 to 95 mGy. A
linear relationship was found between the number of DSB-marking foci/nucleus and
the absorbed dose to the blood for both radionuclides studied. There were only
minor nuclide-specific intra- and inter-subject deviations.
PMID- 25853577
TI - Edoxaban (Savaysa)--the fourth new oral anticoagulant.
PMID- 25853578
TI - Secukinumab (Cosentyx) for psoriasis.
PMID- 25853576
TI - Haplotype phasing and inheritance of copy number variants in nuclear families.
AB - DNA copy number variants (CNVs) that alter the copy number of a particular DNA
segment in the genome play an important role in human phenotypic variability and
disease susceptibility. A number of CNVs overlapping with genes have been shown
to confer risk to a variety of human diseases thus highlighting the relevance of
addressing the variability of CNVs at a higher resolution. So far, it has not
been possible to deterministically infer the allelic composition of different
haplotypes present within the CNV regions. We have developed a novel
computational method, called PiCNV, which enables to resolve the haplotype
sequence composition within CNV regions in nuclear families based on SNP
genotyping microarray data. The algorithm allows to i) phase normal and CNV
carrying haplotypes in the copy number variable regions, ii) resolve the allelic
copies of rearranged DNA sequence within the haplotypes and iii) infer the
heritability of identified haplotypes in trios or larger nuclear families. To our
knowledge this is the first program available that can deterministically phase
null, mono-, di-, tri- and tetraploid genotypes in CNV loci. We applied our
method to study the composition and inheritance of haplotypes in CNV regions of
30 HapMap Yoruban trios and 34 Estonian families. For 93.6% of the CNV loci,
PiCNV enabled to unambiguously phase normal and CNV-carrying haplotypes and
follow their transmission in the corresponding families. Furthermore, allelic
composition analysis identified the co-occurrence of alternative allelic copies
within 66.7% of haplotypes carrying copy number gains. We also observed less
frequent transmission of CNV-carrying haplotypes from parents to children
compared to normal haplotypes and identified an emergence of several de novo
deletions and duplications in the offspring.
PMID- 25853579
TI - Gardasil 9--a broader HPV vaccine.
PMID- 25853580
TI - OTC fluticason nasal spray for allergic rhinitis.
PMID- 25853581
TI - Spiriva Respimat--an oral inhalation spray for COPD.
PMID- 25853582
TI - Macrophage inhibitory cytokine 1 biomarker serum immunoassay in combination with
PSA is a more specific diagnostic tool for detection of prostate cancer.
AB - BACKGROUND: Prostate cancer (PCa) is the most common malignancy among men in the
United States. Though highly sensitive, the often-used prostate-specific antigen
(PSA) test has low specificity which leads to overdiagnosis and overtreatment of
PCa. This paper presents results of a retrospective study that indicates that
testing for macrophage inhibitory cytokine 1 (MIC-1) concentration along with the
PSA assay could provide much improved specificity to the assay. METHODS: The MIC
1 serum level was determined by a novel p-Chip-based immunoassay run on 70
retrospective samples. The assay was configured on p-Chips, small integrated
circuits (IC) capable of storing in their electronic memories a serial number to
identify the molecular probe immobilized on its surface. The distribution of MIC
1 and pre-determined PSA concentrations were displayed in a 2D plot and the
predictive power of the dual MIC-1/PSA assay was analyzed. RESULTS: MIC-1
concentration in serum was elevated in PCa patients (1.44 ng/ml) compared to
normal and biopsy-negative individuals (0.93 ng/ml and 0.88 ng/ml, respectively).
In addition, the MIC-1 level was correlated with the progression of PCa. The area
under the receiver operator curve (AUC-ROC) was 0.81 providing an assay
sensitivity of 83.3% and specificity of 60.7% by using a cutoff of 0.494 for the
logistic regression value of MIC-1 and PSA. Another approach, by defining high
frequency PCa zones in a two-dimensional plot, resulted in assay sensitivity of
78.6% and specificity of 89.3%. CONCLUSIONS: The analysis based on correlation of
MIC-1 and PSA concentrations in serum with the patient PCa status improved the
specificity of PCa diagnosis without compromising the high sensitivity of the PSA
test alone and has potential for PCa prognosis for patient therapy strategies.
PMID- 25853584
TI - Measures of respiratory function correlate with fatigue in ambulatory persons
with multiple sclerosis.
AB - PURPOSE: This article examines the association between measures of respiratory
muscle function and fatigue in individuals with mild-to-moderate disability
multiple sclerosis (MS). METHODS: This was a cross-sectional study of 37
ambulatory volunteers with MS (28 F/9 M, 52.7 +/- 10.2 years, Expanded Disability
Status Scale [EDSS] = 3.5 +/- 1.9). No patients withdrew from the study. Primary
outcome variables included measures of respiratory function: maximal inspiratory
(MIP) and expiratory pressures (MEP), forced vital capacity (FVC), forced
expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV12); and a
self-reported measure of fatigue: the Modified Fatigue Impact Scale (MFIS).
Secondary measures included 6-min walking test (6MWT), a timed stair climb, the
Short Form (SF)-36, the Epworth Sleepiness Scale and the Physical Activity and
Disability Scale (PADS). RESULTS: Significant correlations were shown between
expiratory muscle strength (MEP) and the MFIS total (p < 0.03, r = -0.362) and
between MEP and physical fatigue scores (p < 0.03, r = -0.360), as well as
between MVV12 percent predicted (respiratory muscle endurance) and both the 6MWT
(p = 0.045, r = 0.346) and the Epworth Sleepiness Scale (p = 0.006, r = 0.447).
CONCLUSIONS: Respiratory muscle performance is correlated with perceived fatigue
(MFIS), whereas respiratory endurance correlated to reductions in physical
function and sleep quality among individuals with mild-to-moderate severity MS.
Implications for Rehabilitation Multiple sclerosis (MS) results in peripheral and
respiratory muscle weakness and affected individuals report fatigue as one of
their most disabling symptoms. Expiratory muscle strength was correlated with
self-reported physical fatigue, while respiratory muscle endurance was correlated
with functional performance and sleepiness. Respiratory muscle strength was not
correlated with lung spirometry testing. These findings highlight the importance
of considering the effects of respiratory muscle weakness when evaluating causes
of fatigue among individuals with mild-to-moderate MS.
PMID- 25853583
TI - Chemical characterization of gallstones: an approach to explore the
aetiopathogenesis of gallstone disease in Sri Lanka.
AB - INTRODUCTION: Records on gallstones and associated ailments in Sri Lankan
community are scarce, despite frequent detection of gallstone disease.
Identification of the chemical composition of gallstones in the local setting is
important in defining aetiopathogenic factors which in turn are useful in
implementing therapeutic and preventive strategies. This study aimed to describe
the chemical composition of gallstones and the socio-demographic factors of a
cohort of Sri Lankan patients with gallstone disease. MATERIALS AND METHODS: Data
on clinical and socio-demographic factors, and gallstones removed at surgery were
collected from patients with cholelithiasis admitted to Teaching Hospital,
Peradeniya, Sri Lanka from May 2011 to December 2012. External and cross
sectional morphological features of gallstones were recorded by naked eye
observation. Compositional analysis was carried out by Fourier Transform Infrared
Spectroscopy, X - ray Powder Diffraction, and Atomic Absorption
Spectrophotometry. Scanning Electron Microscopy was used to identify the
microstructure of gallstones. RESULTS: Data of 102 patients were analyzed. Of
them majority (n = 77, 76%) were females with a female: male ratio of 3:1. Mean
age of the study group was 46.1+/-11.6 years. All the patients had primary
gallbladder stones. According to the physical and chemical analysis, majority (n
= 54, 53%) were pigment gallstones followed by mixed cholesterol gallstones (n =
38, 37%). Only 10 (9%) had pure cholesterol gallstones. Calcium bilirubinate,
calcium carbonate and calcium phosphate were the commonest calcium salts
identified in pigment gallstones and core of mixed cholesterol gallstones.
CONCLUSION: Presence of a pigment nidus in gallstones is a common feature in
majority of Sri Lankan patients denoting the possible role of elevated
unconjugated bilirubin in bile on the pathogenesis of GS. Hence it is imperative
to explore this further to understand the aetiopathogenesis of GS among Sri
Lankans.
PMID- 25853585
TI - Surface microstructure of dental implants before and after insertion: an in vitro
study by means of scanning probe microscopy.
AB - INTRODUCTION: The surface microstructure of dental implants affects
osseointegration, which makes their accurate topographic characterization
important. We defined a procedure for evaluation of implant topography before
(pre-) and after (post-) in vitro implantation test in bovine bone. MATERIALS AND
METHODS: The apical morphology of ten implants was analyzed in pre- and post
conditions using atomic force microscopy or 3D profilometry. We extracted four
topographical parameters (two amplitude, 1 spatial, and 1 hybrid) and assessed
the differences by analysis of variance. RESULTS AND DISCUSSION: The implant with
coating (Spline Twist MP-1 HA) was damaged. The two implants with highest pre
amplitude parameters (Pitt Easy VTPS, TLR3815) maintained their character on
testing. Pitt Easy PURETEX and OT-F1 were the only nondamaged implants whose
amplitude parameters increased. The surface area underwent minor changes even
when the texture changed (Tri-Vent, Pitt Easy PURETEX, Exp #1). The implants that
ranked the lowest in all parameters before implantation were DT4013TI, Tri-Vent,
OT-F1, and Exp #2. On testing, DT4013TI showed the highest decrease in values,
whereas Tri-Vent showed the highest increase in surface area. All the
experimental implants showed similar topographic properties both pre- and post
test. CONCLUSION: For most implants, no major changes occurred in surface
topography on implantation. The procedure applied seems promising to evaluate the
degradation of implant surface on insertion.
PMID- 25853586
TI - Distinguishing effects of ultraviolet exposure and chlorination on the horizontal
transfer of antibiotic resistance genes in municipal wastewater.
AB - Growing attention has been paid to the dissemination of antibiotic resistance
genes (ARGs) in wastewater microbial communities; however, the disinfection
processes, as microbial control technologies, have not been evaluated for their
impacts on ARGs transfer. In this study, the effects of ultraviolet (UV)
disinfection and chlorination on the frequency of ARGs transfer have been
explored based on the conjugative transfer model between Gram-negative strains of
E. coli. The results indicated that UV disinfection and chlorination exhibit
distinct influences on the conjugative transfer. Low UV doses (up to 8 mJ/cm2)
had little influence on the frequency of conjugative transfer, and UV exposure
only decreased the bacterial number but did not change the cell permeability. By
comparison, low chlorine doses (up to 40 mg Cl min/L) significantly promoted the
frequency of conjugative transfer by 2-5-fold. The generated chloramine
stimulated the bacteria and improved the cell permeability. More pilus were
induced on the surface of conjugative cells, which acted as pathways for ARGs
transfer. The frequency of ARG transfers was greatly suppressed by high doses of
UV (>10 mJ/cm2) or chlorine (>80 mg Cl min/L).
PMID- 25853587
TI - Sesquiterpene Lactone Composition of Wild and Cultivated Sunflowers and
Biological Activity against an Insect Pest.
AB - Sesquiterpene lactones in sunflowers, Helianthus spp., are important to
interactions with pathogens, weeds, and insects. Across a broad range of
Helianthus annuus, differences in composition of sesquiterpene lactones extracted
from disc florets were found between wild and cultivated sunflowers and also
between distinct groups of inbreds used to produce sunflower hybrids.
Discriminant function analysis showed the presence and relative abundance of
argophyllone B, niveusin B, and 15-hydroxy-3-dehydrodesoxyfruticin were usually
(75%) effective at classifying wild sunflowers, cultivated inbreds, and hybrids.
Argophyllone B reduced the larval mass of the sunflower moth, Homeosoma
electellum, by >30%, but only at a dose greater than that found in florets. Low
doses of mixed extracts from cultivated florets produced a similar (~40%)
reduction in larval mass, suggesting combinations of sesquiterpene lactones act
additively. Although the results support a role for sesquiterpene lactones in
herbivore defense of cultivated sunflowers, additional information is needed to
use these compounds purposefully in breeding.
PMID- 25853588
TI - Rutile phase n- and p-type anodic titania nanotube arrays with square-shaped pore
morphologies.
AB - Rutile-phase TiO2 nanotube arrays without broken walls were formed by annealing
of anodically formed nanotubes in a propane flame at 650 degrees C and in air at
750 degrees C. An unusual morphological transformation was observed from the
ellipsoidal pore-shapes of titania nanotubes grown in aqueous electrolyte to a
square-shaped pore structure subsequent to the anneals. 750 degrees C annealed
nanotubes were found to be lightly p-type, rare in TiO2.
PMID- 25853589
TI - Surfactant-induced assembly of enzymatically-stable peptide hydrogels.
AB - The secondary structure of peptides in the presence of interacting additives is
an important topic of study, having implications in the application of peptide
science to a broad range of modern technologies. Surfactants constitute a class
of biologically relevant compounds that are known to influence both peptide
conformation and aggregation or assembly. We have characterized the secondary
structure of a linear nonapeptide composed of a hydrophobic alanine/phenylalanine
core flanked by hydrophilic acid/amine units. We show that the anionic surfactant
sodium dodecyl sulfate (SDS) induces the formation of beta-sheets and macroscopic
gelation in this otherwise unstructured peptide. Through comparison to related
additives, we propose that SDS-induced secondary structure formation is the
result of amphiphilicity created by electrostatic binding of SDS to the peptide.
In addition, we demonstrate a novel utility of surfactants in manipulating and
stabilizing peptide nanostructures. SDS is used to simultaneously induce
secondary structure in a peptide and to inhibit the activity of a model enzyme,
resulting in a peptide hydrogel that is impervious to enzymatic degradation.
These results complement our understanding of the behavior of peptides in the
presence of interacting secondary molecules and provide new potential pathways
for programmable organization of peptides by the addition of such components.
PMID- 25853590
TI - Characteristics and Outcomes of HIV-Infected Patients With Severe Sepsis:
Continued Risk in the Post-Highly Active Antiretroviral Therapy Era.
AB - OBJECTIVES: Although highly active antiretroviral therapy has led to improved
survival in HIV-infected individuals, outcomes for HIV-infected patients with
sepsis in the post-highly active antiretroviral therapy era are conflicting.
Access to highly active antiretroviral therapy and healthcare disparities
continue to affect outcomes. We hypothesized that HIV-infected patients with
severe sepsis would have worse outcomes compared with their HIV-uninfected
counterparts in a large safety-net hospital where access to healthcare is low and
delivery of critical care is delayed. DESIGN: Secondary analysis of an ongoing
prospective observational study between 2006 and 2010. SETTING: Three adult ICUs
(medical ICU, surgical ICU, and neurologic ICU) at Grady Memorial Hospital,
Atlanta, GA. PATIENTS: Adult patients with severe sepsis in the ICU.
INTERVENTIONS: Baseline patient characteristics and clinical outcomes were
collected. HIV-infected and HIV-uninfected patients with sepsis were compared
using t tests, chi-square tests, and logistic regression; p values less than 0.05
indicated significance. MEASUREMENTS AND MAIN RESULTS: Of 1,095 patients with
severe sepsis enrolled, 165 (15%) were positive for HIV, with a median CD4 count
of 41 (8-167). Twenty-two percent of HIV-infected patients were on highly active
antiretroviral therapy prior to admission, and 80% had a CD4 count less than 200.
HIV-infected patients had a greater hospital mortality (50% vs 38%; p < 0.01).
HIV infection (odds ratio = 1.78; p = 0.005) was an independent predictor of
mortality by multivariate regression modeling after adjusting for age, history of
pneumonia, history of hospital-acquired infection, and history of sepsis.
CONCLUSIONS: HIV-infected patients with severe sepsis continue to suffer worse
outcomes compared with HIV-uninfected patients in a large urban safety-net
hospital caring for patients with limited access to medical care. Further studies
need to be done to investigate the effect of socioeconomic status and mitigate
healthcare disparities among critically ill HIV-infected patients.
PMID- 25853591
TI - A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin
Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill
Adults.
AB - OBJECTIVE: To determine whether regional anticoagulation of continuous renal
replacement therapy circuits using citrate and calcium prolongs circuit life
and/or affects circulating cytokine levels compared with regional anticoagulation
using heparin and protamine. DESIGN: Multicenter, parallel group randomized
controlled trial. SETTING: Seven ICUs in Australia and New Zealand. PATIENTS:
Critically ill adults requiring continuous renal replacement therapy.
INTERVENTIONS: Patients were randomized to receive one of two methods of regional
circuit anticoagulation: citrate and calcium or heparin and protamine.
MEASUREMENTS AND MAIN RESULTS: The primary outcome was functional circuit life
measured in hours, assessed using repeated events survival analysis. In addition,
we measured changes in interleukin-6, interleukin-8, and interleukin-10 blood
levels. We randomized 212 subjects who were treated with 857 continuous renal
replacement therapy circuits (median 2 circuits per patient [interquartile range,
1-6], 390 in citrate group vs 467 in heparin group). The groups were well matched
for baseline characteristics. Patients receiving regional continuous renal
replacement therapy anticoagulation with heparin and protamine were more likely
to experience circuit clotting than those receiving citrate and calcium (hazard
ratio, 2.03 [1.36-3.03]; p < 0.0005; 857 circuits). The median lifespan of the
first study circuit in each patient was 39.2 hours (95% CI, 32.1-48.0 hr) in the
citrate and calcium group versus 22.8 hours (95% CI, 13.3-34.0 hr) in the heparin
and protamine group (log rank p = 0.0037, 204 circuits). Circuit anticoagulation
with citrate and calcium had similar effects on cytokine levels compared with
heparin and protamine anticoagulation. There were more adverse events in the
group assigned to heparin and protamine anticoagulation (11 vs 2; p = 0.011).
CONCLUSIONS: Regional citrate and calcium anticoagulation prolongs continuous
renal replacement therapy circuit life compared with regional heparin and
protamine anticoagulation, does not affect cytokine levels, and is associated
with fewer adverse events.
PMID- 25853592
TI - Selenide Targets to Reperfusing Tissue and Protects It From Injury.
AB - OBJECTIVES: Since blood selenium levels decrease after ischemia and reperfusion
injury, and low blood selenium correlates with negative outcome, we designed and
performed experiments to determine how selenium distribution is affected by
ischemia reperfusion injury. Furthermore, we tested whether different chemical
forms of selenium would affect outcome after ischemia and reperfusion injury. We
also examined the metabolic effects of selenide administration. DESIGN:
Laboratory investigation. SETTING: Animal research laboratory. SUBJECTS: Adult
male C57BL/6 mice. INTERVENTIONS: To determine selenium localization, we
administered tracer doses of radioactive selenium 75 in the form of selenite or
selenide and measured blood and tissue selenium levels after ischemia and
reperfusion injury. Anesthetized mice were subjected to myocardial ischemia
reperfusion injury (coronary artery occlusion for 60 min followed by 5 min of
reperfusion after occlusion was removed) or hindlimb ischemia reperfusion injury
(left leg tourniquet for 90 min followed by 5 min reperfusion after tourniquet
removal). To determine whether exogenous selenium administration could reduce
ischemia reperfusion injury, we synthesized and administered sodium hydroselenide
and sodium selenite solutions (0.05-2.4 mg/kg). Solutions were administered at
the end of coronary artery occlusion but before reperfusion. In order to
determine the metabolic effects of selenide administration, we exposed mice to
hydrogen selenide gas (0-5 ppm) mixed into air (20.95% oxygen) for up to 3 hours.
MEASUREMENTS AND MAIN RESULTS: In targeting assays, we measured blood and tissue
selenium levels. We observed that blood selenium decreases after myocardial
ischemia reperfusion and displays an inverse correlation with injury severity;
selenium accumulation in heart correlates directly with injury severity. We also
measured whether oxidized selenium, selenite, and reduced selenium, selenide,
would target to injured heart tissue in myocardial ischemia reperfusion and
injured leg muscle in a hindlimb model of ischemia reperfusion. Only selenide
targets to injured tissue. We also measured damage after myocardial ischemia
reperfusion injury using morphometry, neutrophil accumulation, blood cardiac
troponin levels, and echocardiography and observed in all assays that selenide
reduced damage to the heart; selenite was not effective. And finally, to assay
metabolism, we measured oxygen consumption, carbon dioxide production, and body
core temperature before, during, and after hydrogen selenide administration. All
measurements indicate that selenide decreases metabolism. CONCLUSIONS: Selenide
targets to reperfusing tissue and reduces reperfusion injury perhaps by affecting
oxygen metabolism.
PMID- 25853594
TI - Diversity goals in medicine: it's time to stop talking and start walking.
PMID- 25853593
TI - Multiple photomorphogenic repressors work in concert to regulate Arabidopsis
seedling development.
AB - Light is both a source of energy and a critically important environmental signal
for plant development. Through decades of research, 2 groups of photomorphogenic
repressors have been identified. The first group is CONSTITUTIVE
PHOTOMORPHOGENIC/DE-ETIOLATED/FUSCA (COP/DET/FUS), which were first identified by
genetic screening and then by purification of protein complexes. Another group is
the Phytochrome-Interacting Factors (PIFs), which were identified by yeast 2
hybrid screens using phyB as bait. How so many factors work together to repress
photomorphogenesis has long been an interesting question. Previously, we
demonstrated that CULLIN4 (CUL4) works as a core factor connecting the COP1-SPA
complexes, the COP9 signalosome (CSN), and the COP10-DDB1-DET1 (CDD) complex.
Recently, we showed that DET1 represses photomorphogenesis through positively
regulating the abundance of PIF proteins in the dark. Dr. Huq and his colleagues
reported that PIFs may enhance the function of COP1-SPA complexes to promote the
degradation of HY5, and thus they synergistically repress photomorphogenesis in
the dark. Though much work still needs to be done, these recent breakthroughs
shed light on the regulatory relationships among these multiple photomorphogenic
repressors.
PMID- 25853595
TI - Poor representation of Blacks, Latinos, and Native Americans in medicine.
AB - BACKGROUND AND OBJECTIVES: In this article, the authors discuss how various
systems in medicine are limiting representation of blacks, Latinos, and Native
Americans. Flat and decreasing percentages of Underrepresented Minorities in
Medicine (URMM), especially in the black and Native American populations, is
concerning for family medicine since members from URMM groups care for minority
and underserved populations in greater numbers. Underrepresentation is not only
noted in the medical community but also in our medical schools when it comes to
numbers of URMM faculty. The changing definition of "disadvantaged" in medical
school admissions has also played a part in limiting URMM representation. In
addition, the Medical College Admissions Test (MCAT) excludes black, Latino, and
Native American students in greater numbers. The authors support these arguments
with evidence from the medical literature. Although unintentional, these systems
effectively limit representation of blacks, Latinos, and Native Americans in
medicine. Effective changes are suggested and can be implemented to ensure that
URMM individuals have equal representation in careers in medicine.
PMID- 25853596
TI - Trends in contraceptive and preconception care in United States ambulatory
practices.
AB - BACKGROUND AND OBJECTIVES: Since 2005, the Centers for Disease Control and
Prevention (CDC), American Academy of Family Physicians (AAFP), and American
College of Obstetricians and Gynecologists (ACOG) have recommended incorporating
family planning and preconception counseling into routine primary care visits. We
compared rates of reproductive health service provision to women aged 15--44
years before and after these guidelines were issued and identified patient,
physician, and visit characteristics associated with the likelihood of provision
of preconception or contraceptive services. METHODS: The National Ambulatory
Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care
Survey (NHAMCS) collected nationally representative data on provision of
preconception and contraceptive services in 1998--2000 and 2009--2010. We used
multivariable logistic regression with appropriate survey weights to assess
changes over time in provision of these services, while controlling for patient
demographics, medical comorbidities, and physician or clinic specialty. RESULTS:
Among ambulatory encounters with women of reproductive age, provision of
reproductive health services increased from 9.5% to 14% between 1998--2000 and
2009--2010, largely due to increased provision of prescription contraception.
CONCLUSIONS: Despite CDC recommendations, a minority of ambulatory visits made by
US women of reproductive age currently include either preconception or
contraceptive services. Future work should focus on understanding barriers and
developing interventions to facilitate incorporation of recommended services into
primary care.
PMID- 25853597
TI - The incorporation of stress management programming into family medicine
residencies-results of a national survey of residency directors: a CERA study.
AB - BACKGROUND AND OBJECTIVES: Residents' stress and burnout is a concern among
family medicine residency programs. Our objective is to assess stress management
options available to family medicine residents. METHODS: In 2012, the Council of
Academic Family Medicine Educational Research Alliance (CERA) e-mailed a survey
to US residency directors. Questions were asked on four types of stress
management programming (SMP): (1) access to counselors, social workers, or mental
health providers, (2) residency support or Balint groups, (3) stress management
lectures or workshops, and (4) residency retreats. We assessed how many programs
contained all four types of SMP and their relationship to the following topics:
stress management techniques for patients, spirituality, mind/body techniques,
and self-care for residents. RESULTS: Of the 212 responses, 29% reported having
all four types of SMP. Eighty-three percent reported stress management lectures
or workshops, and 79% reported residency retreats. Smaller and mid-size
residencies (36%) and residencies in the West (36%) were more likely to have all
four types of SMP. There was a correlation between having didactics, clinical
rotations, and electives on stress management techniques for patient care and
having stress management lectures or workshops for residents. There was
statistical significance between having resident self-care curriculum and (1)
having retreats and (2) stress management lectures or workshops. CONCLUSIONS: It
is necessary to evaluate whether residency programs are providing appropriate
stress management skills for residents that will improve physician wellness and
patient outcomes.
PMID- 25853598
TI - Pharmaceutical industry interactions in family medicine residencies decreased
between 2008 and 2013: a CERA study.
AB - BACKGROUND AND OBJECTIVES: Most medical residents have some interaction with the
pharmaceutical industry. It is not known if this interaction has changed over
time. We determined whether interactions between family medicine residencies and
the pharmaceutical industry have changed in the past 5 years. METHODS: We
surveyed program directors of US family medicine residencies with questions
addressing industry-sponsored gifts, drug samples, access of industry
representatives to trainees, and industry-sponsored residency activities. The
questions were part of a larger 2013 survey administered by the Council of
Academic Family Medicine Educational Research Alliance (CERA). The authors
compared results from 2008 and 2013. RESULTS: The response rate to the 2013 CERA
program director survey was 56% (251/445); 47% (208/445) of surveyed directors
viewed and answered all survey questions. Between 2008 and 2013, residency
programs that accept no gifts or industry-sponsored food increased from 48%
(137/286) to 73% (151/208). Residencies refusing samples increased from 52%
(148/286) to 78% (166/212), and residencies that do not allow industry
representatives to have access to learners increased from 43% (124/286) to 74%
(157/212). Residency programs that forbade industry-sponsored activities remained
stable (67% versus 73%). About half (49%) (101/208)) of programs in 2013
qualified as "pharma-free," compared to 26% (75/286) in 2008. CONCLUSIONS: In
2013, one of two family medicine residencies disallow gifts, drug samples,
interactions between residents and pharmaceutical sales representatives, and
pharmaceutical industry-sponsored activities. This proportion is twice what was
observed in 2008. Restrictions increased in all categories except industry
sponsored activities.
PMID- 25853599
TI - What physicians from diverse specialties know and support in health care reform.
AB - BACKGROUND AND OBJECTIVES: The United States is in an unprecedented era of health
care reform that is pushing medical professionals and medical educators to
evaluate the future of their patients, careers, and the field of medicine. Our
objectives were to describe physician familiarity and knowledge with the Patient
Protection and Affordable Care Act (ACA) and to determine if knowledge is
associated with support and endorsement of the ACA. METHODS: We used a cross
sectional Internet-based survey of 559 physicians practicing in California.
Primary outcomes were physician support and endorsement of ACA: (1) overall
impact on the country (one item) and (2) perceived impact on physician's medical
practice (one item). The primary predictor was knowledge of the ACA as measured
with 10 questions. Other measures included age, gender, race-ethnicity,
specialty, political views, provision of direct care, satisfaction with the
practice of medicine, and compensation type. Descriptive statistics and multiple
variable regression models were calculated. RESULTS: Respondents were 65%
females, and the mean age was 54 years (+/- 9.7). Seventy-seven percent of
physicians understood the ACA somewhat well/very well, and 59% endorsed the ACA,
but 36% of physicians believed that health care reform will most likely hurt
their practice. Primary care physicians were more likely to perceive that the new
law will help their practice, compared to procedural specialties. Satisfaction
with the practice of medicine, political affiliation, compensation type, and more
knowledge of the health care law were independently associated with endorsement
of the ACA. CONCLUSIONS: Endorsement of the ACA varied by specialty, knowledge,
and satisfaction with the practice of medicine.
PMID- 25853600
TI - The effect of dual accreditation on family medicine residency programs.
AB - BACKGROUND AND OBJECTIVES: In 1985, the American Osteopathic Association (AOA)
Board of Trustees agreed to allow residency programs to become dually accredited
by the AOA and Accreditation Council for Graduate Medical Education (ACGME).
Despite the increase in such programs, there has been minimal research comparing
these programs to exclusively ACGME-accredited residencies. This study examines
the association between dual accreditation and suggested markers of quality.
METHODS: Standard characteristics such as regional location, program structure
(community or university based), postgraduate year one (PGY-1) positions offered,
and salary (PGY-1) were obtained for each residency program. In addition, the
faculty to resident ratio in the family medicine clinic and the number of half
days residents spent in the clinic each week were recorded. Initial Match rates
and pass rates of new graduates on the ABFM examination from 2009 to 2013 were
also obtained. Variables were analyzed using chi-square and Student's t test.
Logistic regression models were then created to predict a program's 5-year
aggregate initial Match rate and Board pass rate in the top tertile as compared
to the lowest tertile. RESULTS: Dual accreditation was obtained by 117 (27.0%) of
programs. Initial analyses revealed associations between dually accredited
programs and mean year of initial ACGME program accreditation, regional location,
program structure, tracks, and alternative medicine curriculum. When evaluated in
logistic regression, dual accreditation status was not associated with Match
rates or ABFM pass rates. CONCLUSIONS: By examining suggested markers of program
quality for dually accredited programs in comparison to ACGME-only accredited
programs, this study successfully established both differences and similarities
among the two types.
PMID- 25853601
TI - Collaboration versus competition: an interprofessional education experience.
AB - BACKGROUND AND OBJECTIVES: Our purpose was to assess student, preceptor, and
patient satisfaction with a phased pilot project to introduce interprofessional
education teams into a clinical setting. METHODS: Focus groups with students and
preceptors were used to evaluate acceptability with interprofessional education
teams. We assessed pairings of second-year physician assistant students (PAS2)
with both first- and second-year medical students (MS1, MS2) for three to eight
clinic sessions in a university-based primary care clinic, over a period of 2
years. RESULTS: Twenty students and seven preceptors participated in paired
clinical placement. All students agreed that the pairing was helpful for their
learning. MS felt that they benefitted from the clinical experience of the PAS,
whereas PAS felt that MS brought depth of information from their didactic
learning. All students wished that the clinic sessions could have been more
frequent. Preceptors did not feel precepting two students was more burdensome
than precepting one student but did feel it was important to choose appropriate
students who were interested in working together and teaching each other.
Preceptors felt that the MS2/PAS2 pairing was optimal. CONCLUSIONS: Students and
preceptors were all satisfied with interprofessional teams in the clinical
setting. This model provides one solution to the dilemma of multiple learners
requiring training in a limited number of clinical placement sites.
PMID- 25853602
TI - Teaching cross-cultural communication skills online: a multi-method evaluation.
AB - BACKGROUND AND OBJECTIVES: Cultural competency education is an important and
required part of undergraduate medical education. The objective of this study was
to evaluate whether an online cross-cultural communication module could increase
student use of cross-cultural communication questions that assess the patient's
definition of the problem, the way the problem affects their life, their concerns
about the problem, and what the treatment should be (PACT). METHODS: We used
multi-method assessment of students assigned to family medicine clerkship blocks
that were randomized to receive online cultural competency and PACT training
added to their standard curriculum or to a control group receiving the standard
curriculum only. Outcomes included comparison, via analysis of variance, of
number of PACT questions used during an observed Standardized Patient Exercise,
end-of-year OSCE scores, and qualitative analysis of student narratives. RESULTS:
Students (n=119) who participated in the online module (n=60) demonstrated
increased use of cross-cultural communication PACT questions compared to the
control group (n=59) and generally had positive themes emerge from their
reflective writing. The module had the biggest impact on students who later went
on to match in high communication specialties. CONCLUSIONS: Online teaching of
cross-cultural communication skills can be effective at changing medical student
behavior.
PMID- 25853603
TI - Longitudinal hyperlipidemia outcomes at three student-run free clinic sites.
AB - BACKGROUND AND OBJECTIVES: Student-run free clinics (SRFC) aim to improve health
outcomes of vulnerable populations by providing care to those who have difficulty
accessing the traditional health care safety net. Reducing low density
lipoprotein (LDL) is known to improve health outcomes, yet uninsured patients
remain especially susceptible to poor control. This study describes
hyperlipidemia control over time among patients who received care at three
University of California San Diego Student-Run Free Clinic Project (SRFCP) sites.
METHODS: The authors performed a retrospective review of clinic visits from
August 2006--November 2010 from three sites of the SRFCP. Patients with a new
diagnosis of hyperlipidemia, a baseline LDL level, and at least one follow-up LDL
drawn between 6 weeks and 18 months were included in this study (n=96).
Hyperlipidemia control was analyzed using descriptive statistics, Fisher's exact
tests, paired t tests, and binary logistic regression. RESULTS: At the last
visit, 58.3% (56/96) of patients had achieved LDL goal. LDL decreased from a
baseline mean of 135.8 mg/dL to 101.3mg/dL among the cohort (P<.001). Statins
were used in 86.5% (83/96) of patients. No significant differences were noted
when stratified by language, gender, diabetes comorbidity, homelessness, or
clinic site. When comparing Hispanics and Caucasians only, Hispanic patients had
better LDL control than Caucasians. CONCLUSIONS: This study demonstrates that a
SRFC can effectively manage hyperlipidemia over time, and rates of control can
exceed national standards.
PMID- 25853604
TI - A new way of hearing.
PMID- 25853605
TI - Heart and kidney.
PMID- 25853606
TI - Trends in patient encounters.
PMID- 25853607
TI - Macrophage Migration Inhibitory Factor Deficiency Causes Prolonged Hearing Loss
After Acoustic Overstimulation.
AB - HYPOTHESIS: Macrophage migration inhibitory factor plays an important role in
noise-induced hearing loss. BACKGROUND: Macrophage migration inhibitory factor is
an essential factor in axis formation and neural development. Macrophage
migration inhibitory factor is expressed in the inner ear, but its function
remains to be elucidated. METHODS: Macrophage migration inhibitory factor
deficient mice (MIF(-/-) mice) were used in this study. Wild-type and MIF(-/-)
mice received noise exposure composed of octave band noise. Auditory brainstem
response thresholds were examined before (control) and at 0, 12, and 24 hours and
2 weeks after the intense noise exposure. Morphological findings of cochlear hair
cells were investigated using scanning electron microscopy. Histopathological
examination with hematoxylin and eosin staining and TUNEL assay were also
performed. RESULTS: In both the wild-type and MIF(-/-) mice, acoustic
overstimulation induced significant hearing loss compared with the control level.
Two weeks after the intense noise exposure, the MIF(-/-) mice had an increased
hearing threshold compared with the wild-type mice. Scanning electron microscopy
demonstrated that the outer hair cells in the MIF(-/-) mice were affected 2 weeks
after noise exposure compared with the wild-type mice. TUNEL-positive cells were
identified in the organ of Corti of the MIF(-/-) mice. CONCLUSION: The MIF(-/-)
mice had prolonged hearing loss and significant loss of cochlear hair cells after
intense noise exposure. Macrophage migration inhibitory factor may play an
important role in recovery from acoustic trauma. Management of macrophage
migration inhibitory factor may be a novel therapeutic option for noise-induced
hearing loss.
PMID- 25853608
TI - Effects of Hand Placement Technique on the Video Head Impulse Test (vHIT) in
Younger and Older Adults.
AB - OBJECTIVE: To investigate the effects of hand placement techniques on the video
head impulse test (vHIT) responses (i.e., gain, velocity) in older and younger
adults and to determine intra-rater and inter-rater reliability of the horizontal
vHIT. DESIGN: Descriptive, reliability study. SETTING: University research
laboratory. SUBJECTS: Forty healthy adults grouped by age with negative history
of current or previous vestibular diseases between the ages of 20 and 88 years
(mean = 46.60, standard deviation 23.20). MAIN OUTCOME MEASURES: Three examiners
each used two hand placement techniques (chin and head) to elicit the horizontal
vHIT responses. Both the examiner and hand placement orders were counterbalanced
to account for order and fatigue effects. The outcome measures of interest were
vHIT gain and velocity. RESULTS: A two-way between-subject factorial analysis of
variance revealed a significant main effect for hand placement technique and gain
response. Mean values for vHIT gain were higher for head technique. Significant
main effects were observed for the velocity response for hand placement technique
and age group. Mean velocity values were higher for chin technique and lower
velocities were observed in the older age group. Intra- and inter-rater
reliability scores were consistent for gain values; however, poor to fair inter
rater reliability scores were observed for velocity values. CONCLUSION: It is
suggested that clinical sites select one hand placement technique for the measure
to provide consistency of protocol. Establishing clinical norms using the one
selected method to verify reliability within and across clinicians is suggested
before examination with a disordered population.
PMID- 25853609
TI - Manual Electrode Array Insertion Through a Robot-Assisted Minimal Invasive
Cochleostomy: Feasibility and Comparison of Two Different Electrode Array
Subtypes.
AB - HYPOTHESIS: To evaluate the feasibility and the results of insertion of two types
of electrode arrays in a robotically assisted surgical approach. BACKGROUND:
Recent publications demonstrated that robot-assisted surgery allows the
implantation of free-fitting electrode arrays through a cochleostomy drilled via
a narrow bony tunnel (DCA). We investigated if electrode arrays from different
manufacturers could be used with this approach. METHODS: Cone-beam CT imaging was
performed on five-cadaveric heads after placement of fiducial screws. Relevant
anatomical structures were segmented and the DCA trajectory, including the
position of the cochleostomy, was defined to target the center of the scala
tympani while reducing the risk of lesions to the facial nerve. Med-El Flex 28
and Cochlear CI422 electrodes were implanted on both sides, and their position
was verified by cone-beam CT. Finally, temporal bones were dissected to assess
the occurrence of damage to anatomical structures during DCA drilling. RESULTS:
The cochleostomy site was directed in the scala tympani in 9 of 10 cases. The
insertion of electrode arrays was successful in 19 of 20 attempts. No facial
nerve damage was observed. The average difference between the planned and the
postoperative trajectory was 0.17 +/- 0.19 mm at the level of the facial nerve.
The average depth of insertion was 305.5 +/- 55.2 and 243 +/- 32.1 degrees with
Med-El and Cochlear arrays, respectively. CONCLUSIONS: Robot-assisted surgery is
a reliable tool to allow cochlear implantation through a cochleostomy. Technical
solutions must be developed to improve the electrode array insertion using this
approach.
PMID- 25853610
TI - Vestibular and Balance Impairment Contributes to Cochlear Implant Failure in
Children.
AB - OBJECTIVE: To determine the role of vestibular and balance dysfunction in
children with cochlear implant (CI) failure. STUDY DESIGN: Retrospective case
review. SETTING: Tertiary referral center. PATIENTS: Thirty-five children with CI
failure were compared to 165 children who did not experience CI failure. MAIN
OUTCOME MEASURES: Vestibular function was compared between groups by horizontal
canal function (measured by caloric, rotational, video Head Impulse Testing
[vHIT]), saccular function (vestibular evoked myogenic potentials [VEMP]), and
balance (measured by Bruininks-Oseretsky Test [BOT-2]). RESULTS: Twenty-one
patients completed vestibular and balance testing. Patients with CI failure
demonstrated significantly more abnormal horizontal canal function than those who
did not experience CI failure (caloric: 81 vs. 47%, p = 0.004; rotational/vHIT:
71 vs. 35%, p = 0.001). Absence of bilateral horizontal canal function increased
the odds of CI failure 7.6 times. A greater proportion of children with CI
failure had abnormal saccular function compared to those without CI failure (81
vs. 46%, p = 0.003). Children with CI failure had significantly worse balance
(BOT-2 score: 7.8) than children who did not experience CI failure (BOT-2 score:
12.2) (p < 0.0001). CONCLUSIONS: Vestibular end-organ dysfunction and its
resulting balance impairment have been identified as important risk factors for
CI failure in children. Early identification and treatment of such impairments
may avoid or delay implant failures and prevent children from experiencing
periods of sound deprivation that could impact speech and language acquisition.
PMID- 25853611
TI - A Comparison Between Wireless CROS and Bone-anchored Hearing Devices for Single
sided Deafness: A Pilot Study.
AB - INTRODUCTION: This study compared wireless Contralateral Routing of Signals
(CROS) hearing aid and bone-anchored hearing device (BAHD) in patients with
single-sided deafness. METHODS: Eight adults with single-sided deafness
previously implanted with a BAHD were given a 2-week trial with a CROS hearing
aid and tested in unaided and aided conditions. Both devices were compared on
head shadow effect reduction, speech perception measures in quiet and in noise,
self-assessment questionnaires, and daily diaries. RESULTS: Both the CROS and
BAHD significantly reduced the head shadow effect. QuickSIN scores were
significantly better with noise presented to the poorer ear, as compared to the
better ear, for the unaided condition, the BAHD, and the CROS. Scores showed no
significant differences between the CROS and BAHD with noise presented to the
better ear, but scores with the CROS were significantly poorer than in the
unaided condition with noise presented to the poorer ear. There were no
significant differences between BAHD and CROS for the ratings on the Bern Benefit
in Single-Sided Deafness and Speech Spatial Qualities questionnaires. Both
devices were worn an average of 10 hours per day. Four participants preferred the
CROS for sound quality; three preferred the BAHD for comfort. CONCLUSION:
Comparisons of CROS and BAHD need to be re-evaluated as both technologies have
evolved. In our pilot study, both devices seem comparable, with the CROS avoiding
the risks of surgery, and we recommend a trial of CROS in our center for first
line treatment of single-sided deafness.
PMID- 25853612
TI - Sudden Bilateral Hearing Loss After Cervical and Ocular Vestibular Evoked
Myogenic Potentials.
AB - OBJECTIVE: Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and
oVEMPs) are commonly used in evaluation of neurotologic disorders. We present a
case of sudden bilateral hearing loss immediately after oVEMP and cVEMP testing.
The hearing loss did not recover. To our knowledge, no previous case reports
discuss sudden hearing loss, especially bilateral, associated with VEMP testing.
PATIENT: A single patient with sudden bilateral hearing loss that has persisted
after cVEMP and oVEMP. INTERVENTION: The patient had a history of chronic daily
dizziness. She underwent vestibular function testing that included cVEMP and
oVEMP testing. A significant bilateral sensorineural hearing loss was noted
immediately after cVEMP and oVEMP testing and confirmed with audiometric testing.
Despite the use of oral steroids, her hearing loss did not recover. MAIN OUTCOME
MEASURES: Serial audiograms, calculated maximum total sound energies to each ear.
RESULTS: Pre-VEMP versus post-VEMP audiograms show increased thresholds and
decreased word recognition scores; total sound energy delivered to each ear shows
significant sound exposure. CONCLUSION: Although VEMP testing is thought to be
safe and well tolerated, a significant amount of sound can be delivered to the
cochlea, and certain individuals may be susceptible to acoustic trauma at these
levels. We recommend limits for VEMP stimuli levels and attention to total sound
exposure when multiple trials are used.
PMID- 25853613
TI - Long-term Compliance and Satisfaction With Percutaneous Bone Conduction Devices
in Patients With Congenital Unilateral Conductive Hearing Loss.
AB - OBJECTIVE: Patients with congenital unilateral conductive hearing loss (UCHL) can
either be watchful monitored or treated surgically through the fitting of a
percutaneous bone conduction device (BCD) or, in some cases, atresia repair. The
current study evaluated the long-term compliance and satisfaction with a
percutaneous BCD in this specific population. STUDY DESIGN: Fifty-three
consecutive patients with congenital UCHL treated with a percutaneous BCD in our
tertiary referral center between 1998 and 2011 were identified. Clinical and
audiological data were retrospectively gathered from the patients' files. The
patients were interviewed by telephone about their current device usage status
and were asked to complete the Speech, Spatial and Qualities of Hearing Scale
(SSQ). RESULTS: Compliance with the BCD was 56.6% after a mean follow-up of 7
years. The mean age at implantation of the users (22 years) was significantly
higher than that of the nonusers (10 years). The mean time of device usage before
the patients stopped using the BCD was 5 years. The primary reasons mentioned for
quitting the BCD were experiencing excess background noise and/or subjectively
not receiving enough benefit. Objectively measured features of binaural
processing affected by the BCD were found to correlate with long-term BCD usage.
The SSQ revealed significant improvement in the aided condition compared with the
nonaided condition in the users, in contrast to the nonusers. CONCLUSION: The
current disappointing long-term compliance figures indicate the need for an even
more careful and individualized approach with life-long follow-up when fitting
BCDs in this specific population, especially in children.
PMID- 25853614
TI - A Retrospective Analysis of the Contribution of Reported Factors in Cochlear
Implantation on Hearing Preservation Outcomes.
AB - INTRODUCTION: Preservation of residual hearing is essential to perceive acoustic
stimulation from hybrid cochlear implants (CI). Preservation is a good marker of
atraumatic surgery and residual hearing may be exploited further or enhanced in
future therapies, making complete hearing preservation a desirable goal for all
current CI surgeries. There is large variability in the amount of hearing
preserved and the timeframe over which it is lost after CI. The increase in
numbers of patients with high levels of residual hearing at implantation means
that understanding the variables affecting its preservation is more important
than ever. DATA SOURCES: An English search term with generic and specific items
concerning hearing preservation and cochlear implantation was searched on the Web
of Science service. The search timeframe was limited to 2000 to 2014, with no
language limitations on results. STUDY SELECTION: Hearing preservation,
retrospective CI outcome studies which reported pre- and post-surgical pure-tone
audiometry (PTA) were identified and selected. DATA EXTRACTION: PTA thresholds
were extracted from audiograms or tables and converted into a low-frequency
hearing preservation (LFHP) score. Data for 21 factors associated with hearing
preservation were collected from studies. DATA SYNTHESIS: Factors were included
in a hearing preservation model if they had both a significant bivariate
correlation with LFHP and a significant Kruskal-Wallis H test result (for ordinal
data) or a significant multiple regression analysis result (for scale data).
CONCLUSIONS: Seven factors were found to have a significant effect on hearing
preservation: insertion site, progressive versus stable hearing loss, insertion
angle of electrode, use of intraoperative topical steroids, use of steroids (via
any route/timing), hearing etiology, and electrode array type. The best hearing
preservation options are given.
PMID- 25853615
TI - Analysis of Intraoperative Radiographic Electrode Placement During Cochlear
Implantation.
AB - OBJECTIVE: To investigate the clinical value of intraoperative plain radiographs
in determining correct placement of cochlear implants. PATIENTS: All cochlear
implant insertions over a 10-year period by a single surgeon. INTERVENTIONS:
Cochlear implantation with intraoperative imaging. MAIN OUTCOME MEASURE: Whether
intraoperative imaging affects clinical/surgical management. RESULTS: A
consecutive retrospective review of 207 cochlear implantations performed in 187
patients was performed. All implants performed had intraoperative plain film
imaging. Etiology of hearing loss, surgical variations, gender, age, and implant
type did not affect intraoperative imaging. Four cases were identified where
variations in intraoperative imaging interpreted by the surgeon warranted further
discussion. In one patient, the intraoperative x-ray interpretation missed an
incorrectly placed electrode. Postoperative CT scan confirmed implant electrode
within the superior semicircular canal. In three patients, intraoperative x-ray
results aided management by confirming surgical findings; however, no subsequent
clinical or surgical alterations were made based on imaging. One of these three
patients experienced a noticeable function decline postoperatively that
correlated with altered positioning of the cochlear implant on intraoperative
radiographs. In all surgeries, no changes were made to the electrode placement
based on the intraoperative radiographs. CONCLUSION: Intraoperative plain film
imaging during cochlear implantation, although commonly employed, does not
typically affect clinical management. For select cases, imaging may continue to
be useful based on the surgeon's discretion and intraoperative findings for
confirmatory purposes.
PMID- 25853617
TI - The C-terminal heme regulatory motifs of heme oxygenase-2 are redox-regulated
heme binding sites.
AB - Heme oxygenase-2 (HO2), an enzyme that catalyzes the conversion of heme to
biliverdin, contains three heme regulatory motifs (HRMs) centered at Cys127,
Cys265, and Cys282. Previous studies using the soluble form of human HO2 spanning
residues 1-288 (HO2sol) have shown that a disulfide bond forms between Cys265 and
Cys282 and that, in this oxidized state, heme binds to the catalytic site of
HO2sol via His45. However, various mutational and spectroscopic studies have
confirmed the involvement of cysteine in Fe(3+)-heme binding upon reduction of
the disulfide bond. In an effort to understand how the HRMs are involved in
binding of heme to disulfide-reduced HO2sol, in the work described here, we
further investigated the properties of Fe(3+)-heme bound to HO2. Specifically, we
investigated binding of Fe(3+)-heme to a truncated form of soluble HO2 (residues
213-288; HO2tail) that spans the C-terminal HRMs of HO2 but lacks the catalytic
core. We found that HO2tail in the disulfide-reduced state binds Fe(3+)-heme and
accounts for the spectral features observed upon binding of heme to the disulfide
reduced form of HO2sol that cannot be attributed to heme binding at the catalytic
site. Further analysis revealed that while HO2sol binds one Fe(3+)-heme per
monomer of protein under oxidizing conditions, disulfide-reduced HO2sol binds
slightly more than two. Both Cys265 and Cys282 were identified as Fe(3+)-heme
ligands, and His256 also acts as a ligand to the Cys265-ligated heme.
Additionally, Fe(3+)-heme binds with a much weaker affinity to Cys282 than to
Cys265, which has an affinity much weaker than that of the His45 binding site in
the catalytic core. In summary, disulfide-reduced HO2 has multiple binding sites
with varying affinities for Fe(3+)-heme.
PMID- 25853616
TI - An examination of speech reception thresholds measured in a simulated reverberant
cafeteria environment.
AB - OBJECTIVE: There is increasing demand in the hearing research community for the
creation of laboratory environments that better simulate challenging real-world
listening environments. The hope is that the use of such environments for testing
will lead to more meaningful assessments of listening ability, and better
predictions about the performance of hearing devices. Here we present one
approach for simulating a complex acoustic environment in the laboratory, and
investigate the effect of transplanting a speech test into such an environment.
DESIGN: Speech reception thresholds were measured in a simulated reverberant
cafeteria, and in a more typical anechoic laboratory environment containing
background speech babble. STUDY SAMPLE: The participants were 46 listeners
varying in age and hearing levels, including 25 hearing-aid wearers who were
tested with and without their hearing aids. RESULTS: Reliable SRTs were obtained
in the complex environment, but led to different estimates of performance and
hearing-aid benefit from those measured in the standard environment. CONCLUSIONS:
The findings provide a starting point for future efforts to increase the real
world relevance of laboratory-based speech tests.
PMID- 25853618
TI - Biomimetic synthesis of two salmahyrtisanes: salmahyrtisol A and hippospongide A.
AB - Sesterterpenes with a salmahyrtisane skeleton have been synthesized for the first
time. (-)-Sclareol has been selected as a precursor for the synthesis of two
novel natural products: salmahyrtisol A (1) and hippospongide A (2). Our results
represent a biomimetic approach to obtaining salmahyrtisanes from hyrtiosanes.
Salmahyrtisol A has shown an activity comparable to that of the standard
anticancer drugs in the cell lines A549, HBL-100, HeLa, and SW1573.
PMID- 25853619
TI - Salmonella ghosts expressing enterotoxigenic Escherichia coli k88ab, k88ac, k99,
and fasa fimbrial antigens induce robust immune responses in a mouse model.
AB - BACKGROUND: Bacterial ghosts can be developed as safe and effective vaccines
against bacterial infectious disease such as enterotoxigenic Escherichia coli
(ETEC)-induced diarrhea in neonatal piglets. OBJECTIVE: Immune responses against
a Salmonella ghost expressing ETEC K88ab, K88ac, K99, and FasA antigens with
various adjuvants and inoculation routes were evaluated in mice. ANIMALS AND
METHODS: A ghost cell expressing K88ab, K88ac, K99, and FasA fimbrial antigens of
ETEC on the envelope of ?asd Salmonella typhimurium was constructed as a
candidate vaccine against ETEC infection. To optimize the immunization strategy,
6-week-old female BALB/c mice were inoculated with the ghost and various
adjuvants, and the immune responses against the individual fimbrial antigens were
measured. Blood samples from caudal vein to evaluate serum IgG concentrations and
fecal samples to evaluate mucosal IgA concentrations were collected up to 14
weeks post-prime immunization. RESULTS: All groups with single, double, and
triple inoculations of the ghost showed higher humoral and mucosal immune
responses than the control group. In particular, the groups with intramuscular
double and triple inoculations showed significantly higher immune responses. In
addition, oral inoculation with a combination of the ghost and MONTANIDE IMS 1113
(MI1113) resulted in high and prolonged induction of intestinal IgA levels.
CONCLUSION: These results indicated that both systemic and mucosal immunity
against ETEC fimbrial antigens expressed by the ghost are induced by
intramuscular booster inoculation with the ghost, and that addition of M1113 to
the ghost was found to result in prominent induction of mucosal immunity through
oral inoculation.
PMID- 25853622
TI - Errata.
PMID- 25853623
TI - HLA-A, HLA-B, and HLA-DRB1 Allele and Haplotype Frequencies in Renal Transplant
Candidates in a Population in Southern Brazil.
AB - BACKGROUND: Very few studies have examined the diversity of human leukocyte
antigens (HLA) in the Brazilian renal transplant candidates. METHODS: The
frequencies of the HLA-A, HLA-B, and HLA-DRB1 alleles, haplotypes and phenotypes
were studied in 522 patients with chronic renal failure, renal transplant
candidates, registered at the Transplant Centers in north/northwestern Parana
State, southern Brazil. Patients were classified according to the ethnic group
(319 whites [Caucasians], 134 mestizos [mixed race descendants of Europeans,
Africans, and Amerindians; browns or "pardos"] and 69 blacks). The HLA typing was
performed by the polymerase chain reaction sequence-specific oligonucleotide
method (PCR-SSO), combined with Luminex technology. RESULTS: In the analysis of
the total samples, 20 HLA-A, 32 HLA-B, and 13 HLA-DRB1 allele groups were
identified. The most frequent allele groups for each HLA locus were HLA-A*02
(25.4%), HLA-B*44 (10.9%), and HLA-DRB1*13 (13.9%). The most frequent haplotypes
were HLA-A*01-B*08-DRB1*03 (2.3%), A*02-B*44-DRB1*07 (1.2%), and A*03-B*07
DRB1*11 (1.0%). Significant differences (P < 0.05) were observed in the HLA-A*68,
B*08, and B*58 allele frequencies among ethnic groups. CONCLUSIONS: This study
provides the first data on the HLA-A, HLA-B, and HLA-DRB1 allele, phenotype and
haplotype frequencies of renal transplant candidates in a population in southern
Brazil.
PMID- 25853625
TI - A ruthenium complex as a single-component redox shuttle for electrochemical
photovoltaics.
AB - A primitive version of a ruthenium complex [Ru(bpy)3(2+)] was employed for the
first time as a new conceptual "single-component redox shuttle" for dye
sensitized solar cells. This single shuttle led to a large enhancement of the
open-circuit photovoltage (VOC) to ~940 mV relative to that of conventional
iodine-based shuttle and greatly increased the efficiency of the solar-to
electric energy conversion at lower illumination levels by a factor of ca. 5.6.
PMID- 25853624
TI - IFNbeta secreted by microglia mediates clearance of myelin debris in CNS
autoimmunity.
AB - INTRODUCTION: Multiple sclerosis (MS) is a chronic demyelinating disorder of the
central nervous system (CNS) leading to progressive neurological disability.
Interferon beta (IFNbeta) represents a standard treatment for relapsing-remitting
MS and exogenous administration of IFNbeta exhibits protective effects in
experimentally induced CNS autoimmunity. Also, genetic deletion of IFNbeta in
mice leads to an aggravation of disease symptoms in the MS model of experimental
autoimmune encephalomyelitis (EAE). However, neither the underlying mechanisms
mediating the beneficial effects nor the cellular source of IFNbeta have been
fully elucidated. RESULTS: In this report, a subpopulation of activated microglia
was identified as the major producers of IFNbeta in the CNS at the peak of EAE
using an IFNbeta-fluorescence reporter mouse model. These IFNbeta expressing
microglia specifically localized to active CNS lesions and were associated with
myelin debris in demyelinated cerebellar organotypic slice cultures (OSCs). In
response to IFNbeta microglia showed an enhanced capacity to phagocytose myelin
in vitro and up-regulated the expression of phagocytosis-associated genes.
IFNbeta treatment was further sufficient to stimulate association of microglia
with myelin debris in OSCs. Moreover, IFNbeta-producing microglia mediated an
enhanced removal of myelin debris when co-transplanted onto demyelinated OSCs as
compared to IFNbeta non-producing microglia. CONCLUSIONS: These data identify
activated microglia as the major producers of protective IFNbeta at the peak of
EAE and as orchestrators of IFNbeta-induced clearance of myelin debris.
PMID- 25853626
TI - The Use of Tilted Implant for Posterior Atrophic Maxilla.
AB - PURPOSE: To retrospectively analyze the influence of implant inclination on
marginal bone loss at freestanding implant-supported fixed partial prostheses
(FPPs) over a medium-term period of functional loading. MATERIALS AND METHODS:
Twenty-nine partially edentulous patients with freestanding FPDs supported by two
implants placed in a two-stage procedure comprised the study group. The anterior
implant was placed axially, and the posterior tilted distally. Mesial or distal
inclination of each implant was measured in relation to the vertical axis
perpendicular to the occlusal plane. Average bone loss was compared between
straight and tilted implants, smokers, and nonsmokers. RESULTS: Mean angulation
of the anterior axial-positioned implant was 3.45 degrees distally (range 0-8)
and of the distal implants was 32.83 degrees distally (range 20-50 degrees).
Average bone loss after 1, 3, and 5 years was 0.89 (SD = 0.73), 1.18 (SD = 0.74),
and 1.50 (SD = 0.81), respectively, for axial implants, and 0.98 (SD = 0.69),
1.10 (SD = 0.60) and 1.50 (SD = 0.67) for tilted implants, with no significant
correlation between implant angulation and bone loss. A significant correlation
between implant angulation and annual bone loss was obtained for tilted implants
only (r = 0.52, p = .004).Using Albrektsson criteria, the success rate was 89.6%
(26 out of 29 implants) for straight and 93.1% (27 out of 29) for tilted
implants. CONCLUSION: The study demonstrates no effect of implant angulation on
peri-implant bone loss in the posterior maxilla.
PMID- 25853627
TI - Stress-related anhedonia is associated with ventral striatum reactivity to reward
and transdiagnostic psychiatric symptomatology.
AB - BACKGROUND: Early life stress (ELS) is consistently associated with increased
risk for subsequent psychopathology. Individual differences in neural response to
reward may confer vulnerability to stress-related psychopathology. Using data
from the ongoing Duke Neurogenetics Study, the present study examined whether
reward-related ventral striatum (VS) reactivity moderates the relationship
between retrospectively reported ELS and anhedonic symptomatology. We further
assessed whether individual differences in reward-related VS reactivity were
associated with other depressive symptoms and problematic alcohol use via stress
related anhedonic symptoms and substance use-associated coping. METHOD: Blood
oxygen level-dependent functional magnetic resonance imaging (fMRI) was collected
while participants (n = 906) completed a card-guessing task, which robustly
elicits VS reactivity. ELS, anhedonic symptoms, other depressive symptoms, coping
behavior, and alcohol use behavior were assessed with self-report questionnaires.
Linear regressions were run to examine whether VS reactivity moderated the
relationship between ELS and anhedonic symptoms. Structural equation models
examined whether this moderation was indirectly associated with other depression
symptoms and problematic alcohol use through its association with anhedonia.
RESULTS: Analyses of data from 820 participants passing quality control
procedures revealed that the VS * ELS interaction was associated with anhedonic
symptoms (p = 0.011). Moreover, structural equation models indirectly linked this
interaction to non-anhedonic depression symptoms and problematic alcohol use
through anhedonic symptoms and substance-related coping. CONCLUSIONS: These
findings suggest that reduced VS reactivity to reward is associated with
increased risk for anhedonia in individuals exposed to ELS. Such stress-related
anhedonia is further associated with other depressive symptoms and problematic
alcohol use through substance-related coping.
PMID- 25853629
TI - Learning from instructional explanations: effects of prompts based on the active
constructive-interactive framework.
AB - Although instructional explanations are commonly provided when learners are
introduced to new content, they often fail because they are not integrated into
effective learning activities. The recently introduced active-constructive
interactive framework posits an effectiveness hierarchy in which interactive
learning activities are at the top; these are then followed by constructive and
active learning activities, respectively. Against this background, we combined
instructional explanations with different types of prompts that were designed to
elicit these learning activities and tested the central predictions of the active
constructive-interactive framework. In Experiment 1, N = 83 students were
randomly assigned to one of four combinations of instructional explanations and
prompts. To test the active < constructive learning hypothesis, the learners
received either (1) complete explanations and engaging prompts designed to elicit
active activities or (2) explanations that were reduced by inferences and
inference prompts designed to engage learners in constructing the withheld
information. Furthermore, in order to explore how interactive learning activities
can be elicited, we gave the learners who had difficulties in constructing the
prompted inferences adapted remedial explanations with either (3) unspecific
engaging prompts or (4) revision prompts. In support of the active < constructive
learning hypothesis, we found that the learners who received reduced explanations
and inference prompts outperformed the learners who received complete
explanations and engaging prompts. Moreover, revision prompts were more effective
in eliciting interactive learning activities than engaging prompts. In Experiment
2, N = 40 students were randomly assigned to either (1) a reduced explanations
and inference prompts or (2) a reduced explanations and inference prompts plus
adapted remedial explanations and revision prompts condition. In support of the
constructive < interactive learning hypothesis, the learners who received adapted
remedial explanations and revision prompts as add-ons to reduced explanations and
inference prompts acquired more conceptual knowledge.
PMID- 25853628
TI - KRAS oncogene repression in colon cancer cell lines by G-quadruplex binding
indolo[3,2-c]quinolines.
AB - KRAS is one of the most frequently mutated oncogenes in human cancer, yet
remaining undruggable. To explore a new therapeutic strategy, a library of 5
methyl-indolo[3,2-c]quinoline derivatives (IQc) with a range of alkyldiamine side
chains was designed to target DNA and RNA G-quadruplexes (G4) in the promoter and
5'-UTR mRNA of the KRAS gene. Biophysical experiments showed that di-substituted
IQc compounds are potent and selective KRAS G4 stabilizers. They preferentially
inhibit the proliferation of KRAS mutant cancer cell lines (0.22 < IC50 < 4.80
MUM), down-regulate KRAS promoter activity in a luciferase reporter assay, and
reduce both KRAS mRNA and p21(KRAS) steady-state levels in mutant KRAS colon
cancer cell lines. Additionally, IQcs induce cancer cell death by apoptosis,
explained in part by their capacity to repress KRAS expression. Overall, the
results suggest that targeting mutant KRAS at the gene level with G4 binding
small molecules is a promising anticancer strategy.
PMID- 25853630
TI - Residual metallic contamination of transferred chemical vapor deposited graphene.
AB - Integration of graphene with Si microelectronics is very appealing by offering a
potentially broad range of new functionalities. New materials to be integrated
with the Si platform must conform to stringent purity standards. Here, we
investigate graphene layers grown on copper foils by chemical vapor deposition
and transferred to silicon wafers by wet etching and electrochemical delamination
methods with respect to residual submonolayer metallic contaminations. Regardless
of the transfer method and associated cleaning scheme, time-of-flight secondary
ion mass spectrometry and total reflection X-ray fluorescence measurements
indicate that the graphene sheets are contaminated with residual metals (copper,
iron) with a concentration exceeding 10(13) atoms/cm(2). These metal impurities
appear to be partially mobile upon thermal treatment, as shown by depth profiling
and reduction of the minority charge carrier diffusion length in the silicon
substrate. As residual metallic impurities can significantly alter electronic and
electrochemical properties of graphene and can severely impede the process of
integration with silicon microelectronics, these results reveal that further
progress in synthesis, handling, and cleaning of graphene is required to advance
electronic and optoelectronic applications.
PMID- 25853631
TI - Simultaneous imaging of Zn(2+) and Cu(2+) in living cells based on DNAzyme
modified gold nanoparticle.
AB - Trace Zn(2+) and Cu(2+) in living cells play important roles in the regulation of
biological function. It is significant to simultaneously detect the cellular
Zn(2+) and Cu(2+). Here, we present a novel two-color fluorescence nanoprobe
based on the DNAzymes for simultaneous imaging of Zn(2+) and Cu(2+) in living
cells. The probe consists of a 13 nm gold nanoparticle, DNAzymes that are
specific for Zn(2+) and Cu(2+), and the substrate strands labeled with
fluorophores at the 5' end and quenchers at the 3' end. The fluorescence of the
fluoreophores is quenched both by the gold nanoparticle and the quencher. After
the nanoprobes are transferred into the cells, the substrate strands would be
cleaved in the presence of the Zn(2+) and Cu(2+) target, resulting in
disassociation of the shorter DNA fragments containing fluorophores, which
produce fluorescence signals correlated with the location and concentration of
the Zn(2+) and Cu(2+). The nanoprobe exhibits high specificity, nuclease
stability, and good biocompatibility. Moreover, the nanoprobe can simultaneously
monitor the cellular Zn(2+) and Cu(2+) with an on-site manner, providing the
information on localization and concentration of targets, which is significant to
further research the Zn(2+)- and Cu(2+)-relative cellular events and biological
process. The proposed method has shown great potential in the detection of
multiple metal ions in living cells, which may help us to better understand the
function of metal ions in the fields of biochemistry, molecular biology, and
cellular toxicology.
PMID- 25853632
TI - Vitamin D3 analogs for the treatment of osteoporosis.
AB - Vitamin D supplementation is recommended whenever patients are given therapeutic
drugs for osteoporosis, to make their calcium (Ca) balance positive. Vitamin D is
converted to 25-hydroxyvitamin D in the liver, and then activated to become
1alpha,25-dihydroxyvitamin D in the kidneys. The active vitamin D acts in the
intestine to stimulate Ca absorption and maintain the Ca balance. 2beta-(3
Hydroxypropyloxy)-1alpha,25-dihydroxyvitamin D3 (eldecalcitol) and 2-methylene-19
nor-(20S)-1alpha,25-dihydroxyvitamin D3 (2MD) are newly developed vitamin D
analogs, with a substitution at the 2 position of 1alpha,25-dihydroxyvitamin D3
(calcitriol). Eldecalcitol and 2MD share common structural and biological
characteristics. Both compounds increase serum Ca levels more markedly than
calcitriol, increase bone mineral density (BMD), and improve bone strength in
ovariectomized (OVX) rats. In a randomized, placebo-controlled, double-blind, 1
year clinical trial, eldecalcitol dose-dependently increased lumbar and hip BMD
and suppressed bone turnover markers in patients with osteoporosis. Whereas, 2MD
markedly increased the bone turnover markers, but it did not change the BMD of
postmenopausal women with osteopenia in a 1 year clinical trial. After a
randomized, double-blind, 3 year fracture-prevention trial comparing it with
alfacalcidol, eldecalcitol was approved for the treatment of osteoporosis in
Japan. On the other hand, the manufacturer discontinued the clinical development
of 2MD. In this review, we discuss the similarities and differences between these
2 compounds, and the reasons why different outcomes resulted from their clinical
trials.
PMID- 25853633
TI - A Survey of Experts Regarding the Treatment of Adult Vulvar Lichen Sclerosus.
AB - OBJECTIVE: The objective of this work was to survey physician members and fellows
of the International Society for the Study of Vulvovaginal Disease to determine
current expert opinion regarding the management of adult vulvar lichen sclerosus.
MATERIALS AND METHODS: A cross-sectional design was used. An electronic survey
was emailed to all members and fellows of the International Society for the Study
of Vulvovaginal Disease. Responses were analyzed using univariate methods.
Subgroup analyses were performed to report treatment differences between
gynecologists and dermatologists and between physicians in the United States and
Europe. RESULTS: In total, 128 (42%) of 305 providers responded to the survey.
Analysis was confined to the 114 physician respondents who treat patients with
lichen sclerosus. Clobetasol propionate 0.05% is the most common first-line agent
used in lichen sclerosus (85%). The most common second-line agents used are
tacrolimus (39%), other topical steroids (28%), and intralesional steroids (13%).
Most physicians (59%) start all patients with lichen sclerosus on drug therapy at
an initial visit, regardless of symptoms. Dermatologists are more likely to treat
all patients (both symptomatic and asymptomatic) than gynecologists (p < .01).
Most physicians (64%) continue maintenance therapy in all patients. Gynecologists
are more likely than dermatologists to treat only when patients are symptomatic
versus using maintenance therapy (p = .03). Physicians practicing in the United
States are more likely than those practicing in Europe to treat all patients with
maintenance therapy (p < .01). CONCLUSIONS: Lichen sclerosus management varies
among experts. Variations exist between physician specialties and between those
practicing in different geographic locations. Uncertainty regarding optimal
treatment remains, especially regarding long-term management.
PMID- 25853634
TI - Vulvodynia and Concomitant Femoro-Acetabular Impingement: Long-Term Follow-up
After Hip Arthroscopy.
AB - OBJECTIVE: We hypothesized that in patients with vulvodynia and femoro-acetabular
impingement (FAI), vulvar pain may be generated by the effect of FAI on pelvic
floor structures, and treatment with arthroscopy may improve vulvodynia. We also
sought to identify characteristics of patients whose vulvodynia improved after
arthroscopy. MATERIALS AND METHODS: A case series of patients with vulvodynia and
FAI underwent physical therapy, and, if hip symptoms did not improve,
arthroscopy. Three to 5 years postoperatively, follow-up of outcomes after
arthroscopy on vulvodynia was performed using chart review and patient
questionnaire. Clinical characteristics and pain scores describing patients with
and without vulvodynia improvement were assessed. RESULTS: Twenty-six patients
with generalized unprovoked vulvodynia (GUV) or clitorodynia underwent
arthroscopy for FAI. Six patients, all younger than 30 years, experienced lasting
improvement in vulvodynia. Twenty patients, with an older mean age, longer mean
vulvodynia duration, and mainly severe pain scores, did not experience vulvar
pain improvement after arthroscopy. CONCLUSION: This case series describes
improved vulvodynia outcomes after arthroscopy for FAI in women younger than 30
years. Patients with vulvar pain and coexisting FAI had GUV and clitorodynia.
PMID- 25853635
TI - Highly aging-resistant elastomers doped with antioxidant-loaded clay nanotubes.
AB - A novel aging-resistant styrene-butadiene rubber (SBR) composite is prepared
using the antioxidant N-isopropyl-N'-phenyl-p-phenylenediamine (4010NA) loaded
inside of halloysite clay nanotubes and used as filler. Loading the antioxidant
inside of halloysite allows for its sustained release for nine months in the
rubber matrix. By utilizing modified halloysite, the antioxidant concentration in
this rubber nanoformulation is tripled without causing "blooming" defects.
Furthermore, the halloysite is silanized to enhance its miscibility with rubber.
The aging resistance of SBR-halloysite composites is studied by comparing the
mechanical properties before and after thermal-oxidative aging. A seven-day test
at 90 degrees C shows preservation of mechanical properties, and no 4010NA
blooming is observed, even after one month. Styrene-butadiene rubber with 27 wt %
halloysite loaded with 4010NA shows marked increase in aging resistance and
promising future of halloysite as a functional rubber filler.
PMID- 25853637
TI - Mapsnp: an R package to plot a genomic map for single nucleotide polymorphisms.
AB - Single-nucleotide polymorphism (SNP) is one of the most common sources of genetic
variations of the genome. Currently, SNPs are a main target for most genetic
association studies. Visualizing genomic coordinates of SNPs, including their
physical location relative to their host gene, and the structure of the relevant
transcripts, may provide intuitive supplements to the understanding of their
functions. Nevertheless, to date, no such easy-to-use programming tools exist.
Therefore, we developed an R package, "mapsnp", to plot genomic map for a panel
of SNPs within a genome region of interest, including the relative chromosome
location and the transcripts in the region. mapsnp is a simple and flexible
software package which can be used to visualize a genomic map for SNPs,
integrating a chromosome ideogram, genomic coordinates, SNP locations and SNP
labels.
PMID- 25853636
TI - Regional Strain Analysis with Multidetector CT in a Swine Cardiomyopathy Model:
Relationship to Cardiac MR Tagging and Myocardial Fibrosis.
AB - PURPOSE: To investigate the use of cine multidetector computed tomography (CT) to
detect changes in myocardial function in a swine cardiomyopathy model. MATERIALS
AND METHODS: All animal protocols were in accordance with the Principles for the
Utilization and Care of Vertebrate Animals Used in Testing Research and Training
and approved by the University of Missouri Animal Care and Use Committee. Strain
analysis of cine multidetector CT images of the left ventricle was optimized and
analyzed with feature-tracking software. The standard of reference for strain was
harmonic phase analysis of tagged cardiac magnetic resonance (MR) images at 3.0
T. An animal model of cardiomyopathy was imaged with both cardiac MR and 320
section multidetector CT at a temporal resolution of less than 50 msec. Three
groups were evaluated: control group (n = 5), aortic-banded myocardial
hypertrophy group (n = 5), and aortic-banded and cyclosporine A- treated
cardiomyopathy group (n = 5). Histologic samples of the myocardium were obtained
for comparison with strain results. Dunnett test was used for comparisons of the
concentric remodeling group and eccentric remodeling group against the control
group. RESULTS: Collagen volume fraction ranged from 10.9% to 14.2%; lower
collagen fraction values were seen in the control group than in the
cardiomyopathy groups (P < .05). Ejection fraction and conventional metrics
showed no significant differences between control and cardiomyopathy groups.
Radial strain for both cardiac MR and multidetector CT was abnormal in both
concentric (cardiac MR 25.1% +/- 4.2; multidetector CT 28.4% +/- 2.8) and
eccentric (cardiac MR 23.2% +/- 2.0; multidetector CT 24.4% +/- 2.1) remodeling
groups relative to control group (cardiac MR 18.9% +/- 1.9, multidetector CT
22.0% +/- 1.7, P < .05, all comparisons). Strain values for multidetector CT
versus cardiac MR showed better agreement in the radial direction than in the
circumferential direction (r = 0.55, P = .03 vs r = 0.40, P = .13, respectively).
CONCLUSION: Multidetector CT strain analysis has potential to identify regional
wall-motion abnormalities in cardiomyopathy that is not otherwise detected using
conventional metrics of myocardial function.
PMID- 25853638
TI - Copper-Catalyzed Radical/Radical C(sp 3)-H/P-H Cross-Coupling: alpha
Phosphorylation of Aryl Ketone O-Acetyloximes.
AB - The selective radical/radical cross-coupling of two different organic radicals is
a great challenge due to the inherent activity of radicals. In this paper, a
copper-catalyzed radical/radical C(sp 3)-H/P-H cross-coupling has been developed.
It provides a radical/radical cross-coupling in a selective manner. This work
offers a simple way toward beta-ketophosphonates by oxidative coupling of aryl
ketone o-acetyloximes with phosphine oxides using CuCl as catalyst and PCy3 as
ligand in dioxane under N2 atmosphere at 130 degrees C for 5 h, and yields
ranging from 47% to 86%. The preliminary mechanistic studies by electron
paramagnetic resonance (EPR) showed that, 1) the reduction of ketone o
acetyloximes generates iminium radicals, which could isomerize to alpha-sp(3)
carbon radical species; 2) phosphorus radicals were generated from the oxidation
of phosphine oxides. Various aryl ketone o-acetyloximes and phosphine oxides were
suitable for this transformation.
PMID- 25853639
TI - Quantifying Insulin Therapy Requirements to Preserve Islet Graft Function
Following Islet Transplantation.
AB - A mathematical nonlinear regression model of several parameters (baseline insulin
intake, posttransplant 2-h postprandial blood glucose, and stimulated C-peptide)
from type 1 diabetics with HbA1c <6.5% who do not require insulin therapy and
have no hypoglycemic instances was developed for accurately predicting
supplemental insulin requirements in the posttransplant period. An insulin
deficit threshold of 0.018 U/kg/day was defined as the average first-year
calculated insulin deficit (CID), above which HbA1c rose to >6.5% during year 2
of the posttransplant period. When insulin-untreated subjects were divided into
two groups based on whether the average CID was smaller (group I) or greater
(group II) than the insulin deficit threshold, HbA1c was found to be similar in
the two groups in year 1, but increased significantly in group II to above 6.5%
(with mean glucose of 121.9 mg/dl) but remained below 6.5% in group I subjects
(with mean glucose of 108.7 mg/dl) in year 2 of the follow-up period. The greater
insulin deficit in group II was also associated with a higher susceptibility to
hyperglycemia during periods of low serum Rapamune and Prograf levels (combined
levels below 11.2 and 4.7 ng/ml, respectively). Although the differences between
predicted insulin requirement (PIR) and actual empirical insulin intake in the
insulin-treated subjects were generally small, they were nonetheless sufficient
to identify over- and underinsulinization at each follow-up visit for all
subjects (n = 14 subjects, 135 observations). The newly developed model can
effectively identify underinsulinized islet transplant recipients at risk for
graft dysfunction due to inadequate supplemental insulin intake or those
potentially susceptible to graft function loss due to inadequate
immunosuppression. While less common following islet cell therapy, the model can
also identify overinsulinized subjects who may be at risk for hypoglycemia.
PMID- 25853640
TI - Surface-confined heterometallic triads on the basis of terpyridyl complexes and
design of molecular logic gates.
AB - Surface-confined heterometallic molecular triads (SURHMTs) were fabricated on
SiOx-based solid substrates using optically rich and redox-active Fe-, Os-, and
Ru-based terpyridyl complexes as metalloligands and Cu(2+) ions as linkers.
Optical and electrochemical studies reveal efficient electronic intramolecular
communication in these assemblies. The UV-vis spectra of the triads exhibit a
superposition of the metal-to-ligand charge-transfer bands of individual
complexes, providing a significant enlargement of the optical window, useful for
application. Similarly, cyclic voltammograms of SURHMT layers show a variety of
redox peaks corresponding to individual complexes as well as multi-redox states
at a low potential. Interaction of a representative SURHMT assembly with redox
active NOBF4 was investigated and used as a basis for configuring molecular logic
gates.
PMID- 25853642
TI - Prologue: transformational healing solutions.
AB - In recent years, the provision of wound care for patients has dramatically
improved through the development of new therapeutic options, allowing for a wide
range of wound care therapy choices. In June 2014, an educational International
Surgical Wound Forum (ISWF) was held to present current options in wound care to
a multidisciplinary group of healthcare providers. Topics included negative
pressure wound therapy with instillation and dwell time (NPWTi-d), surgical
incision management (SIM), use of NPWT in the management of the open abdomen,
epidermal skin harvesting, and advanced wound dressings. This supplement provides
in-depth discussion of some of the topics covered at the 2014 ISWF.
PMID- 25853643
TI - Innovation and wound healing.
AB - Innovation in medicine requires unique partnerships between academic research,
biotech or pharmaceutical companies, and health-care providers. While innovation
in medicine has greatly increased over the past 100 years, innovation in wound
care has been slow, despite the fact that chronic wounds are a global health
challenge where there is a need for technical, process and social innovation.
While novel partnerships between research and the health-care system have been
created, we still have much to learn about wound care and the wound-healing
processes.
PMID- 25853644
TI - The evolution of negative pressure wound therapy: negative pressure wound therapy
with instillation.
AB - Complex wounds pose a considerable burden to patients and the health-care system.
The development of negative pressure wound therapy (NPWT) has revolutionised the
treatment of these wounds. NPWT helps create a favourable wound healing
environment by removing infectious material, decreasing oedema and promoting
perfusion and granulation tissue formation. Additionally, NPWT has been reported
to help reduce time to wound closure and length of hospital stay. Modifications
of this foundation of wound care have added intermittent instillation with a
dwell time to NPWT (NPWTi-d). This new system offers more comprehensive wound
care through automated wound irrigation, allowing more control over the wound
environment and the opportunity to deliver topical wound solutions directly to
the affected tissues. A comparison between the two therapies, NPWT and NPWTi-d,
is described, and two real-world applications of NPWTi-d are presented.
PMID- 25853645
TI - Incisional negative pressure wound therapy for high-risk wounds.
AB - With an ageing population and a growing number of people with obesity and/or
undergoing advanced cancer therapies, there is an increasing risk of surgical
site complications including surgical site infections (SSIs). Postoperative
shifting of large mobilised tissue flaps, such as in abdominoplasties, remains a
dreaded complication, particularly following massive weight loss. Besides
negative implications for the patient, surgical site complications result in an
economic burden due to prolonged and repeated wound treatments. Preventative
tools to reduce SSIs are needed. In selected patients at high risk of SSI and/or
wound breakdown, use of incisional NPWT has been shown to actively manage clean,
closed surgical incisions. This article contains a review of scientific and
clinical research relevant to incisional NPWT use over surgical incisions, with
particular emphasis on the common problem of wound breakdown and SSI following
body-contouring surgery in post-bariatric patients. Although there are a growing
number of studies describing use of incisional NPWT in a variety of applications,
including vascular, cardiac and orthopaedic, a literature search revealed few
studies regarding incisional NPWT use post body-contouring surgery. In a clinical
study of seroma formation, less seroma and haematoma formation was reported in
post-bariatric patients who received incisional NPWT, versus the control,
following body-contouring surgery. In another study of widely applied external
NPWT wound dressings over the ventral and lateral trunk following post-bariatric
abdominal dermolipectomy, results showed a significant reduction in exudate
formation, earlier drain removal, and decreased length of hospitalisation,
compared with conventional treatment. Additional controlled studies are needed to
validate the clinical impact of incisional NPWT following body-contouring
surgery, and to determine proper recommendations for its use.
PMID- 25853646
TI - Use of epidermal grafts in wounds: a review of an automated epidermal harvesting
system.
AB - Chronic wounds continue to present a significant challenge to health-care
providers across the globe. Unlike acute wounds, chronic wounds do not proceed
through an orderly process of repair. In recent years, a number of wound healing
treatments, such as dermal replacement scaffolds and negative pressure wound
therapy, have promoted wound healing by stimulating the formation of granulation
tissue. However, until recently there were few modalities designed to promote
epithelialisation of a fully granulated wound. Split-thickness skin grafts
(STSGs) have long been the gold standard for the management of acute wounds, but
have not gained favour in the treatment of chronic wounds for several reasons:
discomfort associated with the donor site, the creation of a second wound (donor
site) in a patient with poor wound-healing potential, and a lack of documented
efficacy for the procedure. Epidermal grafting does not have some of the
limitations encountered with STSG; however, it has not gained wide acceptance, as
previous harvesting techniques were cumbersome and time-consuming. A novel
automated epidermal harvesting system, CelluTome Epidermal Harvesting System
(KCI, an Acelity company, San Antonio, TX, USA), was commercially introduced in
2013. The system yields up to 128 epidermal micrografts that can be easily
harvested at the bedside without anaesthesia and transferred to the recipient
site. The harvesting technique and the use of epidermal grafts in wounds are
reviewed here.
PMID- 25853647
TI - Non-healing foot ulcers in diabetic patients: general and local interfering
conditions and management options with advanced wound dressings.
AB - Medical knowledge about wound management has improved as recent studies have
investigated the healing process and its biochemical background. Despite this,
foot ulcers remain an important clinical problem, often resulting in costly,
prolonged treatment. A non-healing ulcer is also a strong risk factor for major
amputation. Many factors can interfere with wound healing, including the
patient's general health status (i.e., nutritional condition indicated by albumin
levels) or drugs such as steroids that can interfere with normal healing.
Diabetic complications (i.e., renal insufficiency) may delay healing and account
for higher amputation rates observed in diabetic patients under dialysis
treatment. Wound environment (e.g., presence of neuropathy, ischaemia, and
infection) may significantly influence healing by interfering with the
physiological healing cascade and adding local release of factors that may worsen
the wound. The timely and well-orchestrated release of factors regulating the
healing process, observed in acute wounds, is impaired in non-healing wounds that
are blocked in a chronic inflammatory phase without progressing to healing. This
chronic phase is characterised by elevated protease activity (EPA) of
metalloproteinases (MMPs) and serine proteases (e.g., human neutrophil elastase)
that interfere with collagen synthesis, as well as growth factor release and
action. EPA (mainly MMP 9, MMP-8 and elastase) and inflammatory factors present
in the wound bed (such as IL-1, IL-6, and TNFa) account for the catabolic state
of non-healing ulcers. The availability of wound dressings that modulate EPA has
added new therapeutic options for treating non-healing ulcers. The literature
confirms advantages obtained by reducing protease activity in the wound bed, with
better outcomes achieved by using these dressings compared with traditional ones.
New technologies also allow a physician to know the status of the wound bed
environment, particularly EPA, in a clinical setting. These may be helpful in
guiding a clinician's options in treating very difficult-to-heal ulcers.
PMID- 25853648
TI - Analysis of Cell-Surface Receptor Dynamics through Covalent Labeling by Catalyst
Tethered Antibody.
AB - A general technique for introducing biophysical probes into selected receptors in
their native environment is valuable for the study of their structure, dynamics,
function, and molecular interactions. A number of such techniques rely on genetic
engineering, which is not applicable for the study of endogenous proteins, and
such approaches often suffer from artifacts due to the overexpression and bulky
size of the probes/protein tags used. Here we designed novel catalyst-antibody
conjugates capable of introducing small chemical probes into receptor proteins
such as epidermal growth factor receptor (EGFR) and human epidermal growth factor
receptor 2 (HER2) in a selective manner on the surface of living cells. Because
of the selectivity and efficiency of this labeling technique, we were able to
monitor the cellular dynamics and lifetime of HER2 endogenously expressed on
cancer cells. More significantly, the current labeling technique comprises a
stable covalent bond, which combined with a peptide mass fingerprinting analysis
allowed epitope mapping of antibodies on living cells and identification of
potential binding sites of anti-EGFR affibody. Although as yet unreported in the
literature, the binding sites predicted by our labeling method were consistently
supported by the subsequent mutation and binding assay experiments. In addition,
this covalent labeling method provided experimental evidence that HER2 exhibits a
more dynamic structure than expected on the basis of crystallographic analysis
alone. Our novel catalyst-antibody conjugates are expected to provide a general
tool for investigating the protein trafficking, fluctuation, and molecular
interactions of an important class of cell-surface receptors on live cell
surfaces.
PMID- 25853650
TI - Temperature Dependence of the Proteome Profile of the Psychrotolerant Pathogenic
Food Spoiler Bacillus weihenstephanensis Type Strain WSBC 10204.
AB - Bacillus weihenstephanensis is a subspecies of the Bacillus cereus sensu lato
group of spore-forming bacteria known to cause food spoilage or food poisoning.
The key distinguishing phenotype of B. weihenstephanensis is its ability to grow
below 7 degrees C or, from a food safety perspective, to grow and potentially
produce toxins in a refrigerated environment. Comparison of the proteome profile
of B. weihenstephanensis upon its exposure to different culturing conditions can
reveal clues to the mechanistic basis of its psychrotolerant phenotype as well as
elucidate relevant aspects of its toxigenic profile. To this end, the genome of
the type strain B. weihenstephanensis WSBC 10204 was sequenced and annotated.
Subsequently, the proteome profiles of cells grown at either 6 or 30 degrees C
were compared, which revealed considerable differences and indicated several
hundred (uncharacterized) proteins as being subproteome- and/or temperature
specific. In this manner, several processes were newly indicated to be dependent
on growth temperature, such as varying carbon flux routes and a different role
for the urea cycle. Furthermore, a possible post-translational regulatory
function for acetylation was suggested. Toxin production was determined to be
largely independent of growth temperature.
PMID- 25853649
TI - Target-dependent enrichment of virions determines the reduction of high
throughput sequencing in virus discovery.
AB - Viral infections cause many different diseases stemming both from well
characterized viral pathogens but also from emerging viruses, and the search for
novel viruses continues to be of great importance. High-throughput sequencing is
an important technology for this purpose. However, viral nucleic acids often
constitute a minute proportion of the total genetic material in a sample from
infected tissue. Techniques to enrich viral targets in high-throughput sequencing
have been reported, but the sensitivity of such methods is not well established.
This study compares different library preparation techniques targeting both DNA
and RNA with and without virion enrichment. By optimizing the selection of intact
virus particles, both by physical and enzymatic approaches, we assessed the
effectiveness of the specific enrichment of viral sequences as compared to non
enriched sample preparations by selectively looking for and counting read
sequences obtained from shotgun sequencing. Using shotgun sequencing of total DNA
or RNA, viral targets were detected at concentrations corresponding to the
predicted level, providing a foundation for estimating the effectiveness of
virion enrichment. Virion enrichment typically produced a 1000-fold increase in
the proportion of DNA virus sequences. For RNA virions the gain was less
pronounced with a maximum 13-fold increase. This enrichment varied between the
different sample concentrations, with no clear trend. Despite that less
sequencing was required to identify target sequences, it was not evident from our
data that a lower detection level was achieved by virion enrichment compared to
shotgun sequencing.
PMID- 25853651
TI - Molten Au/Ge alloy migration in Ge nanowires.
AB - Herein, we report time-resolved in situ transmission electron microscopy
observation of Au particle melting at a Ge nanowire tip, subsequent forming of
Au/Ge alloy liquid, and its migrating within the Ge nanowire. The migration
direction and position of the Au/Ge liquid can be controlled by the applied
voltage and the migration speed shows a linear deceleration in the nanowire. In a
migration model proposed, the relevant dynamic mechanisms (electromigration,
thermodiffusion, and viscous force, etc.) are discussed in detail. This work
associated with the liquid mass transport in the solid nanowires should provide
new insights into the crystal growth, interface engineering, and fabrication of
the heterogeneous nanostructure-based devices.
PMID- 25853652
TI - DGEclust: differential expression analysis of clustered count data.
AB - We present a statistical methodology, DGEclust, for differential expression
analysis of digital expression data. Our method treats differential expression as
a form of clustering, thus unifying these two concepts. Furthermore, it
simultaneously addresses the problem of how many clusters are supported by the
data and uncertainty in parameter estimation. DGEclust successfully identifies
differentially expressed genes under a number of different scenarios, maintaining
a low error rate and an excellent control of its false discovery rate with
reasonable computational requirements. It is formulated to perform particularly
well on low-replicated data and be applicable to multi-group data. DGEclust is
available at http://dvav.github.io/dgeclust/.
PMID- 25853653
TI - Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune
reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.
AB - Understanding the host immune response during cryptococcal meningitis (CM) is of
critical importance for the development of immunomodulatory therapies. We
profiled the cerebrospinal fluid (CSF) immune-response in ninety patients with
HIV-associated CM, and examined associations between immune phenotype and
clinical outcome. CSF cytokine, chemokine, and macrophage activation marker
concentrations were assayed at disease presentation, and associations between
these parameters and microbiological and clinical outcomes were examined using
principal component analysis (PCA). PCA demonstrated a co-correlated CSF cytokine
and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines.
The presence of this CSF cytokine response was associated with evidence of
increased macrophage activation, more rapid clearance of Cryptococci from CSF,
and survival at 2 weeks. The key components of this protective immune-response
were interleukin (IL)-6 and interferon-gamma, IL-4, IL-10 and IL-17 levels also
made a modest positive contribution to the PC1 score. A second component of co
correlated chemokines was identified by PCA, consisting primarily of monocyte
chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP
1alpha). High CSF chemokine concentrations were associated with low peripheral
CD4 cell counts and CSF lymphocyte counts and were predictive of immune
reconstitution inflammatory syndrome (IRIS). In conclusion CSF cytokine and
chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM.
We speculate that the presence of even minimal Cryptococcus-specific Th1-type
CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes
and monocytes into the central nervous system (CNS), more effective activation of
CNS macrophages and microglial cells, and faster organism clearance; while high
CNS chemokine levels may predispose to over recruitment or inappropriate
recruitment of immune cells to the CNS and IRIS following peripheral immune
reconstitution with ART. These results provide a rational basis for future
studies of immune modulation in CM, and demonstrate the potential of baseline
immune profiling to identify CM patients most at risk of mortality and subsequent
IRIS.
PMID- 25853654
TI - Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model.
AB - Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the
American continent. Herein, we have tested the protective efficacy of a DNA
prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs
were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and
TcG4 antigens plus IL-12- and GM-CSF-encoding plasmids) followed by two doses of
glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with
highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty
pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge
infection antibody response by an ELISA, parasitemia by blood analysis and
xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic
and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG
response (IgG2>IgG1) that was significantly expanded post-infection, and moved to
a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given
TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance
in response to T. cruzi infection. Blood parasitemia, tissue parasite foci,
parasite transmission to triatomines, electrocardiographic abnormalities were
significantly lower in TcVac4-vaccinated dogs than was observed in dogs given
TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the
hallmarks of chronic Chagas disease, were significantly decreased in the
myocardium of TcVac4-vaccinated dogs. We conclude that TcVac4 induced immunity
was beneficial in providing resistance to T. cruzi infection, evidenced by
control of chronic pathology of the heart and preservation of cardiac function in
dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites
from vaccinated/infected animals to triatomines.
PMID- 25853655
TI - Agreement between clinical history method, Orbscan IIz, and Pentacam in
estimating corneal power after myopic excimer laser surgery.
AB - The purpose of this study was to investigate the agreement between the clinical
history method (CHM), Orbscan IIz, and Pentacam in estimating corneal power after
myopic excimer laser surgery. Fifty five patients who had myopic LASIK/PRK were
recruited into this study. One eye of each patient was randomly selected by a
computer-generated process. At 6 months after surgery, postoperative corneal
power was calculated from the CHM, Orbscan IIz total optical power at the 3.0 and
4.0 mm zones, and Pentacam equivalent keratometric readings (EKRs) at 3.0, 4.0,
and 4.5 mm. Statistical analyses included multilevel models, Pearson's
correlation test, and Bland-Altman plots. The Orbscan IIz 3.0-mm and 4.0 mm total
optical power, and Pentacam 3.0-mm, 4.0-mm, and 4.5-mm EKR values had strong
linear positive correlations with the CHM values (r = 0.90-0.94, P = <0.001, for
all comparisons, Pearson's correlation). However, only Pentacam 3.0-mm EKR was
not statistically different from CHM (P = 0.17, multilevel models). The mean 3.0-
and 4.0-mm total optical powers of the Orbscan IIz were significantly flatter
than the values derived from CHM, while the average EKRs of the Pentacam at 4.0
and 4.5 mm were significantly steeper. The mean Orbscan IIz 3.0-mm total optical
power was the lowest keratometric reading compared to the other 5 values. Large
95% LoA was observed between each of these values, particularly EKRs, and those
obtained with the CHM. The width of the 95% LoA was narrowest for Orbscan IIz 3.0
mm total optical power. In conclusion, the keratometric values extracted from
these 3 methods were disparate, either because of a statistically significant
difference in the mean values or moderate agreement between them. Therefore, they
are not considered equivalent and cannot be used interchangeably.
PMID- 25853656
TI - Automated detection of soma location and morphology in neuronal network cultures.
AB - Automated identification of the primary components of a neuron and extraction of
its sub-cellular features are essential steps in many quantitative studies of
neuronal networks. The focus of this paper is the development of an algorithm for
the automated detection of the location and morphology of somas in confocal
images of neuronal network cultures. This problem is motivated by applications in
high-content screenings (HCS), where the extraction of multiple morphological
features of neurons on large data sets is required. Existing algorithms are not
very efficient when applied to the analysis of confocal image stacks of neuronal
cultures. In addition to the usual difficulties associated with the processing of
fluorescent images, these types of stacks contain a small number of images so
that only a small number of pixels are available along the z-direction and it is
challenging to apply conventional 3D filters. The algorithm we present in this
paper applies a number of innovative ideas from the theory of directional
multiscale representations and involves the following steps: (i) image
segmentation based on support vector machines with specially designed multiscale
filters; (ii) soma extraction and separation of contiguous somas, using a
combination of level set method and directional multiscale filters. We also
present an approach to extract the soma's surface morphology using the 3D
shearlet transform. Extensive numerical experiments show that our algorithms are
computationally efficient and highly accurate in segmenting the somas and
separating contiguous ones. The algorithms presented in this paper will
facilitate the development of a high-throughput quantitative platform for the
study of neuronal networks for HCS applications.
PMID- 25853657
TI - Ecological drivers of shark distributions along a tropical coastline.
AB - As coastal species experience increasing anthropogenic pressures there is a
growing need to characterise the ecological drivers of their abundance and
habitat use, and understand how they may respond to changes in their environment.
Accordingly, fishery-independent surveys were undertaken to investigate shark
abundance along approximately 400 km of the tropical east coast of Australia.
Generalised linear models were used to identify ecological drivers of the
abundance of immature blacktip Carcharhinus tilstoni/Carcharhinus limbatus,
pigeye Carcharhinus amboinensis, and scalloped hammerhead Sphyrna lewini sharks.
Results indicated general and species-specific patterns in abundance that were
characterised by a range of abiotic and biotic variables. Relationships with
turbidity and salinity were similar across multiple species, highlighting the
importance of these variables in the functioning of communal shark nurseries. In
particular, turbid environments were especially important for all species at
typical oceanic salinities. Mangrove proximity, depth, and water temperature were
also important; however, their influence varied between species. Ecological
drivers may promote spatial diversity in habitat use along environmentally
heterogeneous coastlines and may therefore have important implications for
population resilience.
PMID- 25853658
TI - Colloidal Silver: Dangerous and Readily Available.
PMID- 25853660
TI - Percutaneous ultrasound guided implantation of VX2 for creation of a rabbit
hepatic tumor model.
AB - Creation of a VX2 tumor model has traditionally required a laparotomy and
surgical implantation of tumor fragments. Open surgical procedures are invasive
and require long procedure times and recovery that can result in post-operative
morbidity and mortality. The purpose of this study is to report the results of a
percutaneous ultrasound guided method for creation of a VX2 model in rabbit
livers. A total of 27 New Zealand white rabbits underwent a percutaneous
ultrasound guided approach, where a VX2 tumor fragment was implanted in the
liver. Magnetic resonance imaging was used to assess for tumor growth and
necropsy was performed to determine rates of tract seeding and metastatic
disease. Ultrasound guided tumor implantation was successful in all 27 rabbits.
One rabbit died 2 days following the implantation procedure. Two rabbits had no
tumors seen on follow-up imaging. Therefore, tumor development was seen in 24/26
(92%) rabbits. During the follow-up period, tract seeding was seen in 8% of
rabbits and 38% had extra-hepatic metastatic disease. Therefore, percutaneous
ultrasound guided tumor implantation safely provides reliable tumor growth for
establishing hepatic VX2 tumors in a rabbit model with decreased rates of tract
seeding, compared to previously reported methods.
PMID- 25853662
TI - Ivermectin cream (Soolantra) for rosacea.
PMID- 25853661
TI - Dose-dependent ATP depletion and cancer cell death following calcium
electroporation, relative effect of calcium concentration and electric field
strength.
AB - BACKGROUND: Electroporation, a method for increasing the permeability of
membranes to ions and small molecules, is used in the clinic with
chemotherapeutic drugs for cancer treatment (electrochemotherapy).
Electroporation with calcium causes ATP (adenosine triphosphate) depletion and
cancer cell death and could be a novel cancer treatment. This study aims at
understanding the relationship between applied electric field, calcium
concentration, ATP depletion and efficacy. METHODS: In three human cell lines-
H69 (small-cell lung cancer), SW780 (bladder cancer), and U937 (leukaemia),
viability was determined after treatment with 1, 3, or 5 mM calcium and eight 99
MUs pulses with 0.8, 1.0, 1.2, 1.4 or 1.6 kV/cm. Fitting analysis was applied to
quantify the cell-killing efficacy in presence of calcium. Post-treatment
intracellular ATP was measured in H69 and SW780 cells. Post-treatment
intracellular ATP was observed with fluorescence confocal microscopy of
quinacrine-labelled U937 cells. RESULTS: Both H69 and SW780 cells showed dose
dependent (calcium concentration and electric field) decrease in intracellular
ATP (p<0.05) and reduced viability. The 50% effective cell kill was found at 3.71
kV/cm (H69) and 3.28 kV/cm (SW780), reduced to 1.40 and 1.15 kV/cm (respectively)
with 1 mM calcium (lower EC50 for higher calcium concentrations). Quinacrine
fluorescence intensity of calcium-electroporated U937 cells was one third lower
than in controls (p<0.0001). CONCLUSIONS: Calcium electroporation dose
dependently reduced cell survival and intracellular ATP. Increasing extracellular
calcium allows the use of a lower electric field. GENERAL SIGNIFICANCE: This
study supports the use of calcium electroporation for treatment of cancer and
possibly lowering the applied electric field in future trials.
PMID- 25853663
TI - Advice for travelers.
PMID- 25853664
TI - In brief: severe bradycardia with sofosbuvir and amiodarone.
PMID- 25853659
TI - Genetically determined height and coronary artery disease.
AB - BACKGROUND: The nature and underlying mechanisms of an inverse association
between adult height and the risk of coronary artery disease (CAD) are unclear.
METHODS: We used a genetic approach to investigate the association between height
and CAD, using 180 height-associated genetic variants. We tested the association
between a change in genetically determined height of 1 SD (6.5 cm) with the risk
of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data
from 18,249 persons, we also examined the risk of CAD associated with the
presence of various numbers of height-associated alleles. To identify putative
mechanisms, we analyzed whether genetically determined height was associated with
known cardiovascular risk factors and performed a pathway analysis of the height
associated genes. RESULTS: We observed a relative increase of 13.5% (95%
confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD
decrease in genetically determined height. There was a graded relationship
between the presence of an increased number of height-raising variants and a
reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74;
95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we
observed significant associations only with levels of low-density lipoprotein
cholesterol and triglycerides (accounting for approximately 30% of the
association). We identified several overlapping pathways involving genes
associated with both development and atherosclerosis. CONCLUSIONS: There is a
primary association between a genetically determined shorter height and an
increased risk of CAD, a link that is partly explained by the association between
shorter height and an adverse lipid profile. Shared biologic processes that
determine achieved height and the development of atherosclerosis may explain some
of the association. (Funded by the British Heart Foundation and others.).
PMID- 25853665
TI - Acute Influences of Bisphenol A Exposure on Hypothalamic Release of Gonadotropin
Releasing Hormone and Kisspeptin in Female Rhesus Monkeys.
AB - Bisphenol A (BPA) is an industrial compound with pervasive distribution in the
environments of industrialized countries. The U.S. Centers for Disease Control
recently found that greater than 90% of Americans carry detectable levels of BPA,
raising concern over the direct influences of this compound on human physiology.
Epidemiologic evidence links elevated BPA serum concentrations to human
reproductive dysfunction, although controlled studies on the acute effect of BPA
exposure on reproductive function are limited, particularly in primates. We
evaluated the effect of direct BPA exposure on female primate hypothalamic
peptide release. Specifically, using a microdialysis method, we examined the
effects of BPA (0.1, 1, and 10nM) directly infused to the stalk-median eminence
on the release of GnRH and kisspeptin (KP) in mid to late pubertal ovarian intact
female rhesus monkeys. We found that the highest level of BPA exposure (10nM)
suppressed both GnRH and KP release, whereas BPA at lower concentrations (0.1 and
1nM) had no apparent effects. In addition, we measured BPA in plasma and
hypothalamic dialysates after an iv bolus injection of BPA (100 MUg/kg). We found
a relatively stable distribution of BPA between the blood and brain (plasma:brain
? 5:1) persists across a wide range of blood BPA concentrations (1-620 ng/mL).
Findings of this study suggest that persistent, high-level exposures to BPA could
impair female reproductive function by directly influencing hypothalamic
neuroendocrine function.
PMID- 25853666
TI - The Effects of High-Fat Diet Exposure In Utero on the Obesogenic and Diabetogenic
Traits Through Epigenetic Changes in Adiponectin and Leptin Gene Expression for
Multiple Generations in Female Mice.
AB - Recent studies demonstrate that epigenetic changes under malnutrition in utero
might play important roles in transgenerational links with metabolic diseases. We
have previously shown that exposure to a high-fat diet (HFD) in utero may cause a
metabolic syndrome-like phenomenon through epigenetic modifications of
Adiponectin and Leptin genes. Because an association of obesity between mother
and offspring endured in multiple generations, we examined whether HFD exposure
in utero might affect the metabolic status of female offspring through
multigenerational epigenetic changes of Adiponectin and Leptin genes and whether
a normal diet in utero for multiple generations might abolish such epigenetic
changes after exposure to a HFD in utero using ICR mice. We observed that the
effect of maternal HFD on offspring over multiple generations in metabolic
syndrome-like phenomenon such as weight and fat mass gain, glucose intolerance,
hypertriglyceridemia, abnormal adiponectin and leptin levels, and hypertension,
were accumulated with expression and epigenetic changes in Adiponectin and Leptin
genes. A normal diet in utero in the subsequent generations after HFD exposure in
utero diminished, and a normal diet in utero for 3 generations completely
abolished, the effect of HFD in utero on weight and fat mass gain, insulin
resistance, serum triglyceride, adiponectin, and leptin levels, with epigenetic
changes of Adiponectin and Leptin genes. Exposure to a HFD in utero might affect
glucose and lipid metabolism of female offspring through epigenetic modifications
to Adiponectin and Leptin genes for multiple generations. Obesogenic and
diabetogenic traits were abolished after a maternal normal diet for 3
generations.
PMID- 25853668
TI - Correction: an integrative computational approach for prioritization of genomic
variants.
AB - [This corrects the article DOI: 10.1371/journal.pone.0114903.].
PMID- 25853667
TI - Propranolol Attenuates Risperidone-Induced Trabecular Bone Loss in Female Mice.
AB - Atypical antipsychotic (AA) drugs cause significant metabolic side effects, and
clinical data are emerging that demonstrate increased fracture risk and bone loss
after treatment with the AA, risperidone (RIS). The pharmacology underlying the
adverse effects on bone is unknown. However, RIS action in the central nervous
system could be responsible because the sympathetic nervous system (SNS) is known
to uncouple bone remodeling. RIS treatment in mice significantly lowered
trabecular bone volume fraction (bone volume/total volume), owing to increased
osteoclast-mediated erosion and reduced osteoblast-mediated bone formation.
Daytime energy expenditure was also increased and was temporally associated with
the plasma concentration of RIS. Even a single dose of RIS transiently elevated
expression of brown adipose tissue markers of SNS activity and thermogenesis,
Pgc1a and Ucp1. Rankl, an osteoclast recruitment factor regulated by the SNS, was
also increased 1 hour after a single dose of RIS. Thus, we inferred that bone
loss from RIS was regulated, at least in part, by the SNS. To test this, we
administered RIS or vehicle to mice that were also receiving the nonselective
beta-blocker propranolol. Strikingly, RIS did not cause any changes in trabecular
bone volume/total volume, erosion, or formation while propranolol was present.
Furthermore, beta2-adrenergic receptor null (Adrb2(-/-)) mice were also protected
from RIS-induced bone loss. This is the first report to demonstrate SNS-mediated
bone loss from any AA. Because AA medications are widely prescribed, especially
to young adults, clinical studies are needed to assess whether beta-blockers will
prevent bone loss in this vulnerable population.
PMID- 25853669
TI - Computational study of a model system of enzyme-mediated [4+2] cycloaddition
reaction.
AB - A possible mechanistic pathway related to an enzyme-catalyzed [4+2] cycloaddition
reaction was studied by theoretical calculations at density functional (B3LYP,
O3LYP, M062X) and semiempirical levels (PM6-DH2, PM6) performed on a model
system. The calculations were carried out for the key [4+2] cycloaddition step
considering enzyme-catalyzed biosynthesis of Spinosyn A in a model reaction,
where a reliable example of a biological Diels-Alder reaction was reported
experimentally. In the present study it was demonstrated that the [4+2]
cycloaddition reaction may benefit from moving along the energetically balanced
reaction coordinate, which enabled the catalytic rate enhancement of the [4+2]
cycloaddition pathway involving a single transition state. Modeling of such a
system with coordination of three amino acids indicated a reliable decrease of
activation energy by ~18.0 kcal/mol as compared to a non-catalytic
transformation.
PMID- 25853671
TI - Sustaining hospital financial health: A role for physician assistant leadership.
PMID- 25853670
TI - Common and distinct impacts of autistic traits and alexithymia on social reward.
AB - According to the social motivation hypothesis of autism, individuals with high
levels of autistic traits experience reduced levels of reward from social
interactions. However, empirical evidence to date has been mixed, with some
studies reporting lower levels of social reward in individuals with Autism
Spectrum Disorder (ASD), and others finding no difference when compared to
typically developing controls. Alexithymia, a subclinical condition associated
with the reduced ability to identify and describe one's own emotions, has been
found to account for other affective difficulties observed inconsistently in
individuals with ASD. The current study used a nonclinical sample (N = 472) to
explore the associations between autistic traits and the value of six types of
social reward, as measured by the Social Reward Questionnaire. In addition, we
measured alexithymia to assess if this accounted for associations between
autistic traits and social reward. There were three main findings. Firstly,
higher levels of autistic traits were associated with significantly less
enjoyment of admiration and sociability, and adding alexithymia to these models
did not account for any additional variance. Secondly, both autistic traits and
alexithymia were uniquely associated with reduced levels of enjoyment of
prosocial interactions and sexual relationships. Thirdly, autistic traits were
associated with higher levels of enjoyment of passivity and negative social
potency, but these associations were no longer significant once alexithymia was
taken into account, suggesting that co-occurring alexithymia accounted for these
apparent associations. Overall, the current findings provide a novel and more
nuanced picture of the relationship between autistic traits and social reward.
PMID- 25853672
TI - Handcuffs.
PMID- 25853673
TI - Pathogenesis and management of diabetic foot ulcers.
AB - Diabetic foot ulcers are a devastating component of diabetes progression and are
caused by loss of glycemic control, peripheral neuropathy, peripheral vascular
disease, and immunosuppression. An estimated 15% of patients with diabetes have
diabetic foot ulcers. This article describes the pathogenesis, diagnosis,
clinical management, and advances in wound treatment for diabetic foot ulcers.
PMID- 25853674
TI - The evolution of chronic opioid therapy and recognizing addiction.
AB - Chronic pain is one of the most common complaints in the United States. Opioids
have become a frequently prescribed treatment for patients with chronic
nonmalignant pain. Concurrently, opioid use disorders have risen to epidemic
levels. Studies investigating iatrogenic opioid addiction have been of limited
quality. Aberrant drug-related behaviors may be warning signs of impending
addiction. Proper screening and close monitoring are essential for managing
patients on opioids for chronic nonmalignant pain.
PMID- 25853675
TI - Various chemical strategies to deceive ants in three Arhopala species
(lepidoptera: Lycaenidae) exploiting Macaranga myrmecophytes.
AB - Macaranga myrmecophytes (ant-plants) are generally well protected from herbivore
attacks by their symbiotic ants (plant-ants). However, larvae of Arhopala
(Lepidoptera: Lycaenidae) species survive and develop on specific Macaranga ant
plant species without being attacked by the plant-ants of their host species. We
hypothesized that Arhopala larvae chemically mimic or camouflage themselves with
the ants on their host plant so that the larvae are accepted by the plant-ant
species of their host. Chemical analyses of cuticular hydrocarbons showed that
chemical congruency varied among Arhopala species; A. dajagaka matched well the
host plant-ants, A. amphimuta did not match, and unexpectedly, A. zylda lacked
hydrocarbons. Behaviorally, the larvae and dummies coated with cuticular
chemicals of A. dajagaka were well attended by the plant-ants, especially by
those of the host. A. amphimuta was often attacked by all plant-ants except for
the host plant-ants toward the larvae, and those of A. zylda were ignored by all
plant-ants. Our results suggested that conspicuous variations exist in the
chemical strategies used by the myrmecophilous butterflies that allow them to
avoid ant attack and be accepted by the plant-ant colonies.
PMID- 25853676
TI - Medically unexplained and explained physical symptoms in the general population:
association with prevalent and incident mental disorders.
AB - BACKGROUND: Clinical studies have shown that Medically Unexplained Symptoms (MUS)
are related to common mental disorders. It is unknown how often common mental
disorders occur in subjects who have explained physical symptoms (PHY), MUS or
both, in the general population, what the incidence rates are, and whether there
is a difference between PHY and MUS in this respect. AIM: To study the prevalence
and incidence rates of mood, anxiety and substance use disorders in groups with
PHY, MUS and combined MUS and PHY compared to a no-symptoms reference group in
the general population. METHOD: Data were derived from the Netherlands Mental
Health Survey and Incidence Study-2 (NEMESIS-2), a nationally representative face
to-face survey of the general population aged 18-64 years. We selected subjects
with explained physical symptoms only (n=1952), with MUS only (n=177), with both
MUS and PHY (n=209), and a reference group with no physical symptoms (n=4168).
The assessment of common mental disorders was through the Composite International
Diagnostic Interview 3.0. Multivariate logistic regression analyses were used to
examine the association between group membership and the prevalence and first
incidence rates of comorbid mental disorders, adjusted for socio-demographic
characteristics. RESULTS: MUS were associated with the highest prevalence rates
of mood and anxiety disorders, and combined MUS and PHY with the highest
prevalence rates of substance disorder. Combined MUS and PHY were associated with
a higher incidence rate of mood disorder only (OR 2.9 (95%CI:1.27,6.74)).
CONCLUSION: In the general population, PHY, MUS and the combination of both are
related to mood and anxiety disorder, but odds are highest for combined MUS and
PHY in relation to substance use disorder. Combined MUS and PHY are related to a
greater incidence of mood disorder. These findings warrant further research into
possibilities to improve recognition and early intervention in subjects with
combined MUS and PHY.
PMID- 25853677
TI - Different prognostic values of plasma Epstein-Barr virus DNA and maximal
standardized uptake value of 18F-FDG PET/CT for nasopharyngeal carcinoma patients
with recurrence.
AB - PURPOSE: To evaluate and compare the prognostic value of Epstein-Barr virus (EBV)
DNA and maximal standard uptake values (SUVmax ) of 18F-fluoro-2-deoxy-D-glucose
positron emission tomography (18F-FDG-PET) in subgroups of nasopharyngeal
carcinoma (NPC) patients with locoregional or distant recurrence. PATIENTS AND
METHODS: A total of 194 patients with recurrent NPC (locoregional recurrence:
107, distant recurrence: 87) were enrolled. Patients took evidence of recurrence
performed with 18F-FDG-PET and an EBV DNA test before salvage treatment. Clinical
parameters, the status of EBV DNA and the value of SUVmax were used for survival
analysis using the Kaplan-Meier method and the Cox proportional hazards
regression model. RESULTS: In the subgroup of patients with locoregional
recurrence, patients with SUVmax<8.65 had significantly better overall survival
(OS) (P=0.005) compared with the patients with SUVmax >=8.65. However, both
elevated EBV DNA load (>=21,100 copies/ml) and distant SUVmax (>=13.55) were
significantly associated with worse OS compared with the patients with EBV DNA
<21,100 copies/ml or distant SUVmax <13.55 for the subgroup with distant
recurrence (P=0.015 and P=0.006, respectively). The predictive ability of EBV DNA
was superior to that of SUVmax (P=0.062). Multivariate analysis showed that
SUVmax was only an independent prognostic factor for OS in patients with
locoregional recurrence (P=0.042), whereas EBV DNA independently predicted OS for
the patients with distant recurrence (P=0.007). For those patients with
undetectable EBV DNA, SUVmax<8.65 was still an independent favorable prognostic
factor (P=0.038). CONCLUSIONS: SUVmax is a useful biomarker for predicting OS in
nasopharyngeal carcinoma patients with locoregional recurrence or with
undetectable EBV DNA. Both distant SUVmax and EBV DNA appear to be independent
predictors of OS in patients with distant recurrence; however, the predictive
ability of EBV DNA was superior to that of SUVmax.
PMID- 25853678
TI - Quantifying regional differences in the length of Twitter messages.
AB - The increasing usage of social media for conversations, together with the
availability of its data to researchers, provides an opportunity to study human
conversations on a large scale. Twitter, which allows its users to post messages
of up to a limit of 140 characters, is one such social media. Previous studies of
utterances in books, movies and Twitter have shown that most of these utterances,
when transcribed, are much shorter than 140 characters. Furthermore, the median
length of Twitter messages was found to vary across US states. Here, we
investigate whether the length of Twitter messages varies across different
regions in the UK. We find that the median message length, depending on grouping,
can differ by up to 2 characters.
PMID- 25853679
TI - Can persistence hunting signal male quality? A test considering digit ratio in
endurance athletes.
AB - Various theories have been posed to explain the fitness payoffs of hunting
success among hunter-gatherers. 'Having' theories refer to the acquisition of
resources, and include the direct provisioning hypothesis. In contrast, 'getting'
theories concern the signalling of male resourcefulness and other desirable
traits, such as athleticism and intelligence, via hunting prowess. We
investigated the association between androgenisation and endurance running
ability as a potential signalling mechanism, whereby running prowess, vital for
persistence hunting, might be used as a reliable signal of male reproductive
fitness by females. Digit ratio (2D:4D) was used as a proxy for prenatal
androgenisation in 439 males and 103 females, while a half marathon race (21km),
representing a distance/duration comparable with that of persistence hunting, was
used to assess running ability. Digit ratio was significantly and positively
correlated with half-marathon time in males (right hand: r = 0.45, p<0.001; left
hand: r = 0.42, p<0.001) and females (right hand: r = 0.26, p<0.01; left hand: r
= 0.23, p = 0.02). Sex-interaction analysis showed that this correlation was
significantly stronger in males than females, suggesting that androgenisation may
have experienced stronger selective pressure from endurance running in males. As
digit ratio has previously been shown to predict reproductive success, our
results are consistent with the hypothesis that endurance running ability may
signal reproductive potential in males, through its association with prenatal
androgen exposure. However, further work is required to establish whether and how
females respond to this signalling for fitness.
PMID- 25853680
TI - A novel DNA biosensor using a ferrocenyl intercalator applied to the potential
detection of human population biomarkers in wastewater.
AB - A new label-free electrochemical DNA (E-DNA) biosensor using a custom synthesized
ferrocenyl (Fc) double-stranded DNA intercalator as a redox marker is presented.
Single-stranded DNA (ssDNA) was co-immobilized on gold electrodes with 6-mecarpto
hexanol to control the surface density of the ssDNA probe, and hybridized with
complementary DNA. The binding of the Fc intercalator to dsDNA was measured by
differential pulse voltammetry. This new biosensor was optimized to allow the
detection of single base pair mismatched sequences, able to detect as low as 10
pM target ssDNA with a dynamic range from 10 pM to 100 nM. DNA extracted from
wastewater was analyzed by quantitative polymerase chain reaction targeting human
specific mitochondrial DNA (mtDNA). The aim of this approach is to enable the
analysis of population biomarkers in wastewater for the evaluation of public
health using wastewater-based epidemiology (WBE). The E-DNA biosensor was
employed to detect human-specific mtDNA from wastewater before and after PCR
amplification. The results demonstrate the feasibility of detecting human DNA
biomarkers in wastewater using the developed biosensor, which may allow the
further development of DNA population biomarkers for public health using WBE.
PMID- 25853681
TI - Risk factors for subdural haematoma in patients with spontaneous intracranial
hypotension.
AB - Subdural haematoma (SDH) is a potentially life-threatening complication in
patients with spontaneous intracranial hypotension (SIH). In serious cases, SIH
patients who present with SDHs develop neurological deficits, a decreased level
of consciousness, or cerebral herniation, and may even require an urgent
neurosurgical drainage. Despite numerous publications on SDHs, few report its
potential risk factors in patients with SIH. In this study, we retrospectively
investigated 93 consecutive SIH patients and divided them into an SDH group (n =
25) and a non-SDH (NSDH) group (n = 68). The clinical and radiographic
characteristics of these 93 patients were analyzed, and then univariate analysis
and further multiple logistic regression analysis were performed to identify the
potential risk factors for the development of SDHs. The univariate analysis
showed that advanced age, male gender, longer clinical course, dural enhancement,
and the venous distension sign were associated with the development of SDHs.
However, multivariate analysis only included the latter three factors. Our study
reveals important radiological manifestations for predicting the development of
SDHs in patients with SIH.
PMID- 25853682
TI - Modular Approach to Reductive C(sp2)-H and C(sp3)-H Silylation of Carboxylic Acid
Derivatives through Single-Pot, Sequential Transition Metal Catalysis.
AB - We report a modular approach to catalytic reductive Csp2-H and Csp3-H silylation
of carboxylic acid derivatives encompassing esters, ketones, and aldehydes.
Choice of either an Ir(I)/Rh(I) or Rh(I)/Rh(I) sequence leads to either
exhaustive reductive ester or reductive ketone/aldehyde silylation, respectively.
Notably, a catalyst-controlled direct formation of doubly reduced silyl ethers is
presented, specifically via Ir-catalyzed exhaustive hydrosilylation. The
resulting silyl ethers undergo Csp2-H and benzylic Csp3-H silylation in a single
vessel.
PMID- 25853684
TI - Emotions, narratives, and ethical mindfulness.
AB - Clinical care is laden with emotions, from the perspectives of both clinicians
and patients. It is important that emotions are addressed in health professions
curricula to ensure that clinicians are humane healers as well as technical
experts. Emotions have a valuable and generative role in health professional
ethics education.The authors have previously described a narrative ethics
pedagogy, the aim of which is to develop ethical mindfulness. Ethical mindfulness
is a state of being that acknowledges everyday ethics and ethically important
moments as significant in clinical care, with the aim of enabling ethical
clinical practice. Using a sample narrative, the authors extend this concept to
examine five features of ethical mindfulness as they relate to emotions: (1)
being sensitized to emotions in everyday practice, (2) acknowledging and
understanding the ways in which emotions are significant in practice, (3) being
able to articulate the emotions at play during ethically important moments, (4)
being reflexive and acknowledging both the generative aspects and the limitations
of emotions, and (5) being courageous.The process of writing and engaging with
narratives can lead to ethical mindfulness, including the capacity to understand
and work with emotions. Strategies for productively incorporating emotions in
narrative ethics teaching are described. This can be a challenging domain within
medical education for both educators and health care students and thus needs to
be addressed sensitively and responsibly. The potential benefit of educating
health professionals in a way which addresses emotionality in an ethical
framework makes the challenges worthwhile.
PMID- 25853683
TI - Pro-aggregant Tau impairs mossy fiber plasticity due to structural changes and
Ca(++) dysregulation.
AB - INTRODUCTION: We used an inducible mouse model expressing the Tau repeat domain
with the pro-aggregant mutation DeltaK280 to analyze presynaptic Tau pathology in
the hippocampus. RESULTS: Expression of pro-aggregant Tau(RDDelta) leads to
phosphorylation, aggregation and missorting of Tau in area CA3. To test
presynaptic pathophysiology we used electrophysiology in the mossy fiber tract.
Synaptic transmission was severely disturbed in pro-aggregant Tau(RDDelta) and
Tau-knockout mice. Long-term depression of the mossy fiber tract failed in pro
aggregant Tau(RDDelta) mice. We observed an increase in bouton size, but a
decline in numbers and presynaptic markers. Both pre-and postsynaptic structural
deficits are preventable by inhibition of Tau(RDDelta) aggregation. Calcium
imaging revealed progressive calcium dysregulation in boutons of pro-aggregant
Tau(RDDelta) mice. In N2a cells we observed this even in cells without tangle
load, whilst in primary hippocampal neurons transient Tau(RDDelta) expression
alone caused similar Ca(++) dysregulation. Ultrastructural analysis revealed a
severe depletion of synaptic vesicles pool in accordance with synaptic
transmission impairments. CONCLUSIONS: We conclude that oligomer formation by
Tau(RDDelta) causes pre- and postsynaptic structural deterioration and Ca(++)
dysregulation which leads to synaptic plasticity deficits.
PMID- 25853685
TI - Contemplating medicine during the Third Reich: scaffolding professional identity
formation for medical students.
AB - PROBLEM: The moral failures of physicians and the medical establishment in
Germany and Austria during the Third Reich challenge medicine and medical
education in a way few other events do. They compel medical educators to ensure
that lessons learned from contemplating medicine during the Third Reich be
integrated into current and future physicians' professional identities. Most
health professions education programs, however, have not adopted this study
domain in their curricula. APPROACH: The authors describe a new curriculum module
"The Holocaust and Medicine"-and its implementation in October 2013 at Bar-Ilan
University Faculty of Medicine in the Galilee, Safed, Israel, as a requirement
for all medical students (starting with the class of 2017). This innovative
module integrates historical facts, guided reflection, flipped classroom
pedagogy, and program evaluation efforts. It spans 20 months of the preclinical
curriculum, embedded within a doctoring course and a medical humanities
longitudinal course and integrated within the clinical sciences blocks. OUTCOMES:
The evaluation approach will seek to measure changes in learners' knowledge and
attitudes, capture their experience with the module, and assess the module's
contribution to their identities as future healers. NEXT STEPS: This module aims
to sensitize learners to medicine's fundamental dilemmas (e.g., prejudice,
assisted reproduction and suicide, physicians in war), ideally enhancing critical
reflection on the potential danger of "slippery slopes." The authors propose that
contemplation of medicine after the Holocaust and the implications for
contemporary practice should be an integral component of health professions
education to promote humanistic, ethically responsible practice.
PMID- 25853686
TI - Comics and medicine: peering into the process of professional identity formation.
AB - PROBLEM: Medical students experience transformative personal and professional
changes during medical school. The medical education community has much to learn
about how students perceive these changes, which can be dramatic and profound.
APPROACH: Over the past six years (2009-2014), the author has taught a course on
medical graphic narratives (or comics) to fourth-year medical students. Comics
synergistically combine words and images to tell stories and provide an effective
vehicle for helping students reflect on and give voice to varied experiences. In
this course, students critically read and discuss medically themed comics and
create their own original comic depicting a formative experience from medical
school. OUTCOMES: To date, 58 students have taken the course, and each has
produced an original comic. The author conducted a thematic analysis of their
comics and identified the following themes: (1) how I found my niche, (2) the
medical student as patient, (3) reflections on a transformative experience, (4)
connecting with a patient, and (5) the triumphs and challenges of becoming a
doctor. Pre/post course assessments indicate that students believe creating a
comic can significantly improve a variety of doctoring skills and attitudes,
including empathy, communication, clinical reasoning, writing, attention to
nonverbal cues, and awareness of physician bias. Students' comics reveal the
impact of formative events on their professional identity formation. NEXT STEPS:
Medical educators should explore additional ways to effectively integrate comics
into medical school curricula and develop robust tools for evaluating their short
and long-term impact.
PMID- 25853687
TI - Considering context in academic medicine: differences in demographic and
professional characteristics and in research productivity and advancement metrics
across seven clinical departments.
AB - PURPOSE: To understand the disciplinary contexts in which faculty work, the
authors examined demographics, professional characteristics, research
productivity, and advancement across seven clinical departments at Harvard
Medical School (HMS) and nationally. METHOD: HMS analyses included faculty from
seven clinical departments-anesthesiology, medicine, neurology, pediatrics,
psychiatry, radiology, and surgery-in May 2011 (N = 7,304). National analyses
included faculty at 141 U.S. medical schools in the same seven departments as of
December 31, 2011 (N = 91,414). The authors used chi-square and Wilcoxon Mann
Whitney tests to compare departmental characteristics. RESULTS: Heterogeneity in
demographics, professional characteristics, and advancement across departments
was observed in HMS and national data. At HMS, psychiatry had the highest
percentage of underrepresented minority faculty at 6.6% (75/1,139). In
anesthesiology, 24.2% (128/530) of faculty were Asian, whereas in psychiatry only
7.9% (90/1,139) were (P < .0001). Female faculty were the majority in pediatrics
and psychiatry, whereas in surgery 26.3% (172/654) of the faculty were female (P
< .0001). At HMS, surgery, radiology, and neurology had the shortest median times
to promotion and the highest median number of publications, H-index, and second
degree centrality. Neurology also had the highest percentage of faculty who had
been principal investigators on a National Institutes of Health-funded grant.
CONCLUSIONS: There were differences in demographics, professional
characteristics, and advancement across clinical departments at HMS and
nationally. The context in which faculty work, of which department is a proxy,
should be accounted for in research on faculty career outcomes and diversity
inclusion in academic medicine.
PMID- 25853688
TI - Professional identity formation: creating a longitudinal framework through TIME
(Transformation in Medical Education).
AB - The University of Texas System established the Transformation in Medical
Education (TIME) initiative to reconfigure and shorten medical education from
college matriculation through medical school graduation. One of the key changes
proposed as part of the TIME initiative was to begin emphasizing professional
identity formation (PIF) at the premedical level. The TIME Steering Committee
appointed an interdisciplinary task force to explore the fundamentals of PIF and
to formulate strategies that would help students develop their professional
identity as they transform into physicians. In this article, the authors describe
the task force's process for defining PIF and developing a framework, which
includes 10 key aspects, 6 domains, and 30 subdomains to characterize the
complexity of physician identity. The task force mapped this framework onto three
developmental phases of medical education typified by the undergraduate student,
the clerkship-level medical student, and the graduating medical student. The task
force provided strategies for the promotion and assessment of PIF for each
subdomain at each of the three phases, in addition to references and resources.
Assessments were suggested for student feedback, curriculum evaluation, and
theoretical development. The authors emphasize the importance of longitudinal,
formative assessment using a combination of existing assessment methods. Though
not unique to the medical profession, PIF is critical to the practice of
exemplary medicine and the well-being of patients and physicians.
PMID- 25853689
TI - The Johns Hopkins learning environment scale: measuring medical students'
perceptions of the processes supporting professional formation.
AB - PURPOSE: To construct a new measure to assess students' perceptions of the
medical school learning environment (LE). METHOD: In 2012, students at Johns
Hopkins University School of Medicine completed a survey containing 32 LE items.
Additional questions asked about overall perception of the LE, personal growth,
and recommending the school to a friend. Validity evidence for content, response
process, internal structure, and relation to other variables was collected for
interpretation of scores. RESULTS: Of 465 students surveyed, 377 (81%) completed
all LE items. Exploratory factor analysis yielded the 28-item Johns Hopkins
Learning Environment Scale (JHLES) with seven factors/subscales: community of
peers, faculty relationships, academic climate, meaningful engagement, mentoring,
inclusion and safety, and physical space. Students' overall JHLES scores ranged
from 51 to 139, of a possible 28 to 140, with a mean (SD) of 107 (15). Overall
scores and most subscale scores did not differ significantly by gender or
racial/ethnic background, but did differ significantly by overall perception of
the LE (P <= .001) and increased incrementally as overall perception improved.
Overall JHLES scores were significantly higher for students with higher personal
growth scores and students who would recommend the school (both P < .001).
Subscale scores for all seven factors increased with improved overall perception
of the LE (all P <= .005). CONCLUSIONS: The JHLES is a new measure to assess
students' perceptions of the medical school LE, with supporting validity evidence
and content describing the social, relational, and academic processes of medical
school that support students' professional formation.
PMID- 25853690
TI - A review of literature on medical students and scholarly research: experiences,
attitudes, and outcomes.
AB - PURPOSE: The aim of medical student research programs is to develop interest in
and competencies related to scholarly research within future physicians. Although
schools invest in these programs, there is currently no consensus regarding what
benefits they confer. The goal of this review is to characterize students'
perceptions of research programs during medical school as well as the outcomes
attributed to these programs to provide recommendations for their optimization.
METHOD: In June 2013, the authors reviewed the literature (1950-June 2013) and
identified 20 reports that provided original data delineating undergraduate
medical students' primarily self-reported experiences with, outcomes related to,
and attitudes toward research. RESULTS: Students generally perceive their medical
school research experiences to be positive in terms of stimulating research
interest and developing scholarly research abilities. The majority of students
author at least one article, and first-author publications occur more frequently
as formal research experiences lengthen. Elective experiences do not differ from
mandatory experiences in terms of student satisfaction or productivity. Several
studies uncovered negative student perceptions regarding their research
experience, including too little acknowledgment, time, and faculty interaction.
Published studies were deficient in characterizing effects on future research
engagement in participants. CONCLUSIONS: These findings suggest that formal
medical student research programs can be optimized by improving the recognition
of student effort, promoting student-mentor interaction, and allowing students
the option to increase the duration of the research experience. Future studies
are needed to determine whether these programs affect research participation and
productivity later in participants' careers.
PMID- 25853691
TI - Membrane proteome analysis of glioblastoma cell invasion.
AB - Glioblastoma multiforme (GBM) tumor invasion is facilitated by cell migration and
degradation of the extracellular matrix. Invadopodia are actin-rich structures
that protrude from the plasma membrane in direct contact with the extracellular
matrix and are proposed to participate in epithelial-mesenchymal transition. We
characterized the invasiveness of 9 established GBM cell lines using an
invadopodia assay and performed quantitative mass spectrometry-based proteomic
analyses on enriched membrane fractions. All GBM cells produced invadopodia, with
a 65% difference between the most invasive cell line (U87MG) and the least
invasive cell line (LN229) (p = 0.0001). Overall, 1,141 proteins were identified
in the GBM membrane proteome; the levels of 49 proteins correlated with cell
invasiveness. Ingenuity Pathway Analysis predicted activation "cell movement" (z
score = 2.608, p = 3.94E(-04)) in more invasive cells and generated a network of
invasion-associated proteins with direct links to key regulators of invadopodia
formation. Gene expression data relating to the invasion-associated proteins
ITGA5 (integrin alpha5), CD97, and ANXA1 (annexin A1) showed prognostic
significance in independent GBM cohorts. Fluorescence microscopy demonstrated
ITGA5, CD97, and ANXA1 localization in invadopodia assays, and small interfering
RNA knockdown of ITGA5 reduced invadopodia formation in U87MG cells. Thus,
invasion-associated proteins, including ITGA5, may prove to be useful anti
invasive targets; volociximab, a therapeutic antibody against integrin
alpha5beta1, may be useful for treatment of patients with GBM.
PMID- 25853692
TI - Increase in both CD14-positive and CD15-positive myeloid-derived suppressor cell
subpopulations in the blood of patients with glioma but predominance of CD15
positive myeloid-derived suppressor cells in glioma tissue.
AB - Myeloid-derived suppressor cells (MDSCs), defined as CD33-positive major
histocompatibility complex class II-negative cells, are increased in a variety of
human tumors and are associated with immunosuppression. Myeloid-derived
suppressor cells can be further subdivided into CD14-positive monocytic MDSC and
CD15-positive granulocytic MDSC (polymorphonuclear MDSC) subpopulations. Here we
analyzed MDSC subsets in the blood and tumor tissue of patients with glioma,
including the most malignant variant, glioblastoma multiforme (GBM). CD33
positive major histocompatibility complex class II-negative MDSCs in blood from
21 patients with glioma and 12 healthy individuals were phenotyped and quantified
by flow cytometry. Myeloid populations of the monocytic MDSC and
polymorphonuclear MDSC phenotypes were both significantly increased in the blood
of patients with GBM versus healthy controls. The myeloid activation markers CD80
and PD-L1 could not be detected on either of these MDSC subsets; CD124, CD86, and
CD40 were detected at similar levels on MDSCs in patients with glioma and healthy
donors. By contrast, in tumor cell suspensions, the MDSC population consisted
almost exclusively of CD15-positive cells. Immunohistochemistry confirmed
infiltration of CD15-positive major histocompatibility complex class II-negative
cells in glioma tissue samples. These data support a role for cells with an MDSC
phenotype in the blood and tumor microenvironment of patients with GBM.
PMID- 25853693
TI - Neuropathologic features of suicide victims who presented with acute poststroke
depression: significance of association with neurodegenerative disorders.
AB - To investigate the neuropathologic characteristics of poststroke depression (PSD)
leading to suicide, we retrospectively selected deceased subjects who had been
diagnosed as having early PSD. Cases were divided into subjects who had committed
suicide and those who had not. Neuropathologic examinations, including
immunohistochemistry, were conducted. Twenty-four subjects fulfilled criteria for
early PSD; 11 of these had committed suicide, and the other 13 had not. Lesion
type, size of stroke, and location of stroke were variable but did not differ
significantly between the groups. Alzheimer disease-related pathology stages also
did not differ between the groups. Argyrophilic grain disease was found in both
the suicide group (6 of 11) and the nonsuicide group (2 of 13); there were 2
highly possible cases of early progressive supranuclear palsy in the suicide
group. Together, argyrophilic grain disease and progressive supranuclear palsy
were found significantly more frequently in suicide cases than in nonsuicide
cases (p = 0.01). These data suggest that overlapping 4-repeat tauopathies, which
include argyrophilic grain disease and progressive supranuclear palsy, might be
an important aggravating factor of PSD that could lead to suicide. The presence
of other neurodegenerative diseases does not preclude PSD because the prevalence
of these diseases in older persons suggests that they might often occur
concomitantly.
PMID- 25853694
TI - CDKN2A loss is associated with shortened overall survival in lower-grade (World
Health Organization Grades II-III) astrocytomas.
AB - Lower-grade (World Health Organization Grades II and III) gliomas vary widely in
clinical behavior and are classified as astrocytic, oligodendroglial, or mixed.
Anaplasia depends greatly on mitotic activity, with CDKN2A loss considered as the
most common mechanism for cell cycle dysregulation. We investigated whether loss
of the CDKN2A gene is associated with overall survival across pathologically and
genetically defined glioma subtypes. After adjustment for IDH mutation, sex, and
age, CDKN2A deletion was strongly associated with poorer overall survival in
astrocytomas but not in oligodendrogliomas or oligoastrocytomas. Molecular
classification of astrocytomas by IDH mutation, TP53 mutation, and /or ATRX loss
of expression revealed that CDKN2A loss in IDH/TP53 mutated tumors was strongly
associated with worse overall survival. CDKN2A loss in IDH mutated tumors with
ATRX loss was only weakly associated with worse overall survival. These findings
suggest that CDKN2A testing may provide further clinical aid in lower-grade
glioma substratification beyond IDH mutation and 1p19q codeletion status,
particularly in IDH/TP53 mutated astrocytomas.
PMID- 25853695
TI - Neuronal and axonal loss in normal-appearing gray matter and subpial lesions in
multiple sclerosis.
AB - Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the
CNS. Multiple sclerosis lesions include significant demyelination of the gray
matter, which is thought to be a major contributor to both physical and cognitive
impairment. Subpial (Type III) lesions are the most common demyelinated cortical
lesions. We investigated neurodegenerative features of subpial lesions in
cerebral cortex samples from 11 patients with MS and 6 nondemented non-MS
controls. There were no significant differences in neuron and axon density
between normally myelinated normal-appearing gray matter (NAGM) and Type III MS
lesions. Neurons were 11.2% smaller in Type III lesions than in NAGM in the
cingulate cortex only; Type III lesions contained 25.4% fewer NeuN-positive
neurons compared with control cortex. Neurons in MS NAGM were 13.6% smaller than
those in control cortex. Finally, the same regions, immunostained with anti
SMI312 antibodies, showed reduced axon densities in Type III lesions (-31.4%) and
NAGM (-33.0%) compared with controls. In conclusion, both NAGM and Type III
lesions showed neurodegenerative changes, but they had no consistent differences
in neuronal and axonal alterations. This suggests that neurodegeneration in the
cerebral cortex of patients with MS may be independent of cortical demyelination.
PMID- 25853696
TI - Elafin Reverses Pulmonary Hypertension via Caveolin-1-Dependent Bone
Morphogenetic Protein Signaling.
AB - RATIONALE: Pulmonary arterial hypertension is characterized by endothelial
dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling,
and increased elastase activity. Synthetic elastase inhibitors reverse
experimental pulmonary hypertension but cause hepatotoxicity in clinical studies.
The endogenous elastase inhibitor elafin attenuates hypoxic pulmonary
hypertension in mice, but its potential to improve endothelial function and BMPR2
signaling, and to reverse severe experimental pulmonary hypertension or vascular
pathology in the human disease was unknown. OBJECTIVES: To assess elafin-mediated
regression of pulmonary vascular pathology in rats and in lung explants from
patients with pulmonary hypertension. To determine if elafin amplifies BMPR2
signaling in pulmonary artery endothelial cells and to elucidate the underlying
mechanism. METHODS: Rats with pulmonary hypertension induced by vascular
endothelial growth factor receptor blockade and hypoxia (Sugen/hypoxia) as well
as lung organ cultures from patients with pulmonary hypertension were used to
assess elafin-mediated reversibility of pulmonary vascular disease. Pulmonary
arterial endothelial cells from patients and control subjects were used to
determine the efficacy and mechanism of elafin-mediated BMPR2 signaling.
MEASUREMENTS AND MAIN RESULTS: In Sugen/hypoxia rats, elafin reduced elastase
activity and reversed pulmonary hypertension, judged by regression of right
ventricular systolic pressure and hypertrophy and pulmonary artery occlusive
changes. Elafin improved endothelial function by increasing apelin, a BMPR2
target. Elafin induced apoptosis in human pulmonary arterial smooth muscle cells
and decreased neointimal lesions in lung organ culture. In normal and patient
pulmonary artery endothelial cells, elafin promoted angiogenesis by increasing
pSMAD-dependent and -independent BMPR2 signaling. This was linked mechanistically
to augmented interaction of BMPR2 with caveolin-1 via elafin-mediated
stabilization of endothelial surface caveolin-1. CONCLUSIONS: Elafin reverses
obliterative changes in pulmonary arteries via elastase inhibition and caveolin-1
dependent amplification of BMPR2 signaling.
PMID- 25853697
TI - Endobronchial coils for severe emphysema are effective up to 12 months following
treatment: medium term and cross-over results from a randomised controlled trial.
AB - BACKGROUND: There is a clinical need for therapeutic options to reduce
hyperinflation associated with severe emphysema. Endobronchial Coils (coils) are
nitinol devices implanted bronchoscopically under fluoroscopic guidance to re
tension the lung. We report the medium term effectiveness and safety of coils in
a study of patients with emphysema. METHODS: Forty five subjects with severe
airflow obstruction and hyperinflation received bilateral sequential treatment
with coils (30 day interval between treatments) as part of a randomised
controlled trial with a primary endpoint 90 days after the final treatment
(Clinicaltrials.gov NCT01334307). Further assessments were made at 180 and 360
days and in this study the primary outcome was the effect of coil treatment on
the St. George's Respiratory Questionnaire (SGRQ) 360 days following treatment.
RESULTS: At 360 days following treatment, there was an improvement in the SGRQ
score of -6.1+/-14.0 points (p = 0.01) compared to baseline. Improvements in
secondary outcomes were seen with increases in forced expiratory volume in the
first second of 8.9 +/-22.2% (p = 0.002) and 6-minute walking distance of 34.1+/
52.4m (p = 0.003). The safety profile was acceptable out to 360 days post
treatment. CONCLUSIONS: Statistically and clinically meaningful benefits in
quality of life, exercise capacity and pulmonary function in patients treated
with coils are sustained twelve months after treatment. TRIAL REGISTRATION
INFORMATION: Clinicaltrials.gov NCT01334307.
PMID- 25853698
TI - Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis
patients carrying a G551D mutation.
AB - BACKGROUND: Airway microbiota composition has been clearly correlated with many
pulmonary diseases, and notably with cystic fibrosis (CF), an autosomal genetic
disorder caused by mutation in the CF transmembrane conductance regulator (CFTR).
Recently, a new molecule, ivacaftor, has been shown to re-establish the
functionality of the G551D-mutated CFTR, allowing significant improvement in lung
function. OBJECTIVE AND METHODS: The purpose of this study was to follow the
evolution of the airway microbiota in CF patients treated with ivacaftor, using
quantitative PCR and pyrosequencing of 16S rRNA amplicons, in order to identify
quantitative and qualitative changes in bacterial communities. Three G551D
children were followed up longitudinally over a mean period of more than one year
covering several months before and after initiation of ivacaftor treatment.
RESULTS: 129 operational taxonomy units (OTUs), representing 64 genera, were
identified. There was no significant difference in total bacterial load before
and after treatment. Comparison of global community composition found no
significant changes in microbiota. Two OTUs, however, showed contrasting
dynamics: after initiation of ivacaftor, the relative abundance of the anaerobe
Porphyromonas 1 increased (p<0.01) and that of Streptococcus 1 (S. mitis group)
decreased (p<0.05), possibly in relation to the anti-Gram-positive properties of
ivacaftor. The anaerobe Prevotella 2 correlated positively with the pulmonary
function test FEV-1 (r=0.73, p<0.05). The study confirmed the presumed positive
role of anaerobes in lung function. CONCLUSION: Several airway microbiota
components, notably anaerobes (obligate or facultative anaerobes), could be
valuable biomarkers of lung function improvement under ivacaftor, and could shed
light on the pathophysiology of lung disease in CF patients.
PMID- 25853701
TI - The hypocholesterolemic and hormone modulation effects of isoflavones alone or co
fermented with probiotic bacteria in hypercholesterolemic rats model.
AB - This study aimed to investigate the beneficial effect of isoflavones alone or
probiotics-co-fermented isoflavones on serum and hepatic lipid profile, serum
steroid (SHs) and thyroid hormones (THs) of hypercholesterolemic rats (N = 48).
Animals were fed for 8 weeks with probiotics-co-fermented isoflavones or
isoflavones alone, beside high-fat-high-cholesterol diet. Serum was analyzed for
cholesterols, triglycerides (TG), SHs and THs. Results demonstrated that the
given treatments significantly decreased serum total-cholesterol (TC), low
density-lipoprotein-cholesterol (LDL-C), high-density-lipoprotein-cholesterol
(HDL-C), LDL/HDL ratio, and increased TG, compared to controls. The probiotics-co
fermented isoflavones decreased TC, LDL-C and LDL/HDL ratio more effectively than
isoflavones alone. Also, both isoflavones treatments induced a hyperthyroidism
state, as the levels of T-T4, T-T3 and fT3 significantly increased. In addition,
these treatments decreased testosterone and increased cortisol levels. Thus,
isoflavones-containing-treatments, particularly probiotics-co-fermented
isoflavones, could reduce CVD incidence by controlling lipid profile; and this
control could in part be due to modulation of SHs and THs.
PMID- 25853700
TI - Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide
production and protects from oxidative stress-associated endothelial cell injury.
AB - INTRODUCTION: Several studies demonstrated that endothelium dependent
vasodilatation is impaired in cardiovascular and chronic kidney diseases because
of oxidant stress-induced nitric oxide availability reduction. The Mediterranean
diet, which is characterized by food containing phenols, was correlated with a
reduced incidence of cardiovascular diseases and delayed progression toward end
stage chronic renal failure. Previous studies demonstrated that both red and
white wine exert cardioprotective effects. In particular, wine contains Caffeic
acid (CAF), an active component with known antioxidant activities. AIM OF THE
STUDY: The aim of the present study was to investigate the protective effect of
low doses of CAF on oxidative stress-induced endothelial injury. RESULTS: CAF
increased basal as well as acetylcholine-induced NO release by a mechanism
independent from eNOS expression and phosphorylation. In addition, low doses of
CAF (100 nM and 1 MUM) increased proliferation and angiogenesis and inhibited
leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the
uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects
exerted by CAF on endothelial cells may be at least in part ascribed to
modulation of NO release and by decreased ROS production. In an experimental
model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased
tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.
CONCLUSION: The results of the present study suggest that CAF, at very low
dosages similar to those observed after moderate white wine consumption, may
exert a protective effect on endothelial cell function by modulating NO release
independently from eNOS expression and phosphorylation. CAF-induced NO modulation
may limit cardiovascular and kidney disease progression associated with oxidative
stress-mediated endothelial injury.
PMID- 25853702
TI - Nanostructural effects on polymer and water dynamics in cellulose biocomposites:
(2)h and (13)c NMR relaxometry.
AB - Improved moisture stability is desired in cellulose biocomposites. In order to
clarify nanostructural effects, a new approach is presented where water and
polymer matrix mobilities are characterized separately. Nanocomposites from
cellulose nanofibers (CNF) in the xyloglucan (XG) biopolymer matrix are
investigated at different hydration states. Films of XG, CNF, and CNF/XG
composites are subjected to detailed (2)H and (13)C NMR relaxation studies. Since
the (2)H NMR signal arises from heavy water and the (13)C signal from the
polysaccharides, molecular water and polymer dynamics is for the first time
investigated separately. In the neat components, (2)H transverse relaxation (T2)
data are consistent with water clustering at the CNF fibril surfaces, but bulk
spread of moisture in XG. The new method results in a description of water
interaction with the nanoscale phases. At low hydration, water molecules at the
CNF/XG interface exhibit higher water mobility than in neat CNF or XG, due to
locally high water concentration. At the same time, CNF-associated interphase
segments of XG show slower NMR-dynamics than that in neat XG.
PMID- 25853703
TI - External validation and calibration of IVFpredict: a national prospective cohort
study of 130,960 in vitro fertilisation cycles.
AB - BACKGROUND: Accurately predicting the probability of a live birth after in vitro
fertilisation (IVF) is important for patients, healthcare providers and policy
makers. Two prediction models (Templeton and IVFpredict) have been previously
developed from UK data and are widely used internationally. The more recent of
these, IVFpredict, was shown to have greater predictive power in the development
dataset. The aim of this study was external validation of the two models and
comparison of their predictive ability. METHODS AND FINDINGS: 130,960 IVF cycles
undertaken in the UK in 2008-2010 were used to validate and compare the Templeton
and IVFpredict models. Discriminatory power was calculated using the area under
the receiver-operator curve and calibration assessed using a calibration plot and
Hosmer-Lemeshow statistic. The scaled modified Brier score, with measures of
reliability and resolution, were calculated to assess overall accuracy. Both
models were compared after updating for current live birth rates to ensure that
the average observed and predicted live birth rates were equal. The
discriminative power of both methods was comparable: the area under the receiver
operator curve was 0.628 (95% confidence interval (CI): 0.625-0.631) for
IVFpredict and 0.616 (95% CI: 0.613-0.620) for the Templeton model. IVFpredict
had markedly better calibration and higher diagnostic accuracy, with calibration
plot intercept of 0.040 (95% CI: 0.017-0.063) and slope of 0.932 (95% CI: 0.839
1.025) compared with 0.080 (95% CI: 0.044-0.117) and 1.419 (95% CI: 1.149-1.690)
for the Templeton model. Both models underestimated the live birth rate, but this
was particularly marked in the Templeton model. Updating the models to reflect
improvements in live birth rates since the models were developed enhanced their
performance, but IVFpredict remained superior. CONCLUSION: External validation in
a large population cohort confirms IVFpredict has superior discrimination and
calibration for informing patients, clinicians and healthcare policy makers of
the probability of live birth following IVF.
PMID- 25853704
TI - Nephropathy, but not Angiographically Proven Retinopathy, is Associated with
Neutrophil to Lymphocyte Ratio in Patients with Type 2 Diabetes.
AB - BACKGROUND: Type 2 Diabetes Mellitus is a leading cause of end stage renal
disease in the worldwide. Inflammation is regarded as one of the main reasons for
the progression of diabetes complications. We aimed to evaluate the association
of neutrophil to lymphocyte ratio (NLR) as indicator of systemic inflammation
with diabetic retinopathy and nephropathy. PATIENTS AND METHODS: This is a cross
sectional study of 114 prevalent type 2 diabetic subjects. All of the patients
underwent detailed examination for the presence of diabetic retinopathy and
nephropathy. Diabetic retinopathy was approved and classified according to
findings based on flouresceint fundal angiography results. Estimated glomerular
filtration rate (eGFR) and microalbumin to creatinine ratio were calculated to
establish the diabetic nephropathy. NLR was calculated as ratio of absolute
neutrophil count to absolute lymphocyte count. RESULTS: Retinopathy was present
in 55 (48.2%) out of 114 patients, whereas nephropathy was present in 62 patients
(54.3%). NLR was significantly higher in patients with nephropathy than in
patients without nephropathy. NLR was also positively correlated with CRP
(p=0.017, r=0.224) and microalbuminuria (p=0.016, r=0.257) whereas negatively
correlated with eGFR (p<0.001, r=-0.337) values in the whole cohort. NLR was
independent predictors for diabetic nephropathy, whereas it did not appear as an
independent associate of diabetic retinopathy. CONCLUSION: NLR and diabetic
nephropathy have an independent association between them whereas there was no
independent association between NLR with retinopathy in type 2 diabetic patients.
PMID- 25853705
TI - Type 1 diabetes mellitus and exercise in competitive athletes.
AB - AIMS: The number of patients with type 1 diabetes mellitus who are actively
participating in competitive sports is increasing. Here, we aimed to assess
individual experiences of competitive athletes with type 1 diabetes and to
compare these experiences with current recommendations. METHODS: A survey of 20
competitive athletes with type 1 diabetes, categorized as endurance (n=10) and
non-endurance (n=10) athletes, was performed. RESULTS: Endurance and non
endurance athletes did not differ in gender distribution, age, body mass index,
and known diabetes duration. Self-reported target blood glucose values prior to
exercise were lower in non-endurance than in endurance athletes (195+/-34 vs.
137+/-28 mg/dl, P=0.001). The majority of all athletes experienced activity
induced hypo- and hyperglycemic events, independently of exercise type. However,
endurance athletes used additional carbohydrate units to prevent activity-induced
hypoglycemic events more frequently without monitoring their blood glucose levels
than non-endurance athletes (50% vs. 0%, P=0.01). The reduction of the insulin
dose on training and competition days compared to days without exercise was
similar for endurance and non-endurance athletes. CONCLUSION: These results point
to a very individual adaption of the athlete's therapy during training and
competition. However, there are distinct differences in diabetes management
between endurance and non-endurance athletes.
PMID- 25853706
TI - Human Islets Exhibit Electrical Activity on Microelectrode Arrays (MEA).
AB - This study demonstrates for the first time that the microelectrode array (MEA)
technique allows analysis of electrical activity of islets isolated from human
biopsies. We have shown before that this method, i.e., measuring beta cell
electrical activity with extracellular electrodes, is a powerful tool to assess
glucose responsiveness of isolated murine islets. In the present study, human
islets were shown to exhibit glucose-dependent oscillatory electrical activity.
The glucose responsiveness could be furthermore demonstrated by an increase of
insulin secretion in response to glucose. Electrical activity was increased by
tolbutamide and inhibited by diazoxide. In human islets bursts of electrical
activity were markedly blunted by the Na(+) channel inhibitor tetrodotoxin which
does not affect electrical activity in mouse islets. Thus, the MEA technique
emerges as a powerful tool to decipher online the unique features of human
islets.Additionally, this technique will enable research with human islets even
if only a few islets are available and it will allow a fast and easy test of
metabolic integrity of islets destined for transplantation.
PMID- 25853707
TI - Temporal stability of genetic variability and differentiation in the three-spined
stickleback (Gasterosteus aculeatus).
AB - Temporal variation in allele frequencies, whether caused by deterministic or
stochastic forces, can inform us about interesting demographic and evolutionary
phenomena occurring in wild populations. In spite of the continued surge of
interest in the genetics of three-spined stickleback (Gasterosteus aculeatus)
populations, little attention has been paid towards the temporal stability of
allele frequency distributions, and whether there are consistent differences in
effective size (Ne) of local populations. We investigated temporal stability of
genetic variability and differentiation in 15 microsatellite loci within and
among eight collection sites of varying habitat type, surveyed twice over a six
year time period. In addition, Nes were estimated with the expectation that they
would be lowest in isolated ponds, intermediate in larger lakes and largest in
open marine sites. In spite of the marked differences in genetic variability and
differentiation among the study sites, the temporal differences in allele
frequencies, as well as measures of genetic diversity and differentiation, were
negligible. Accordingly, the Ne estimates were temporally stable, but tended to
be lower in ponds than in lake or marine habitats. Hence, we conclude that allele
frequencies in putatively neutral markers in three-spined sticklebacks seem to be
temporally stable - at least over periods of few generations - across a wide
range of habitat types differing markedly in levels of genetic variability,
effective population size and gene flow.
PMID- 25853708
TI - Comparative whole-genome analysis of clinical isolates reveals characteristic
architecture of Mycobacterium tuberculosis pangenome.
AB - The tubercle complex consists of closely related mycobacterium species which
appear to be variants of a single species. Comparative genome analysis of
different strains could provide useful clues and insights into the genetic
diversity of the species. We integrated genome assemblies of 96 strains from
Mycobacterium tuberculosis complex (MTBC), which included 8 Indian clinical
isolates sequenced and assembled in this study, to understand its pangenome
architecture. We predicted genes for all the 96 strains and clustered their
respective CDSs into homologous gene clusters (HGCs) to reveal a hard-core, soft
core and accessory genome component of MTBC. The hard-core (HGCs shared amongst
100% of the strains) was comprised of 2,066 gene clusters whereas the soft-core
(HGCs shared amongst at least 95% of the strains) comprised of 3,374 gene
clusters. The change in the core and accessory genome components when observed as
a function of their size revealed that MTBC has an open pangenome. We identified
74 HGCs that were absent from reference strains H37Rv and H37Ra but were present
in most of clinical isolates. We report PCR validation on 9 candidate genes
depicting 7 genes completely absent from H37Rv and H37Ra whereas 2 genes shared
partial homology with them accounting to probable insertion and deletion events.
The pangenome approach is a promising tool for studying strain specific genetic
differences occurring within species. We also suggest that since selecting
appropriate target genes for typing purposes requires the expected target gene be
present in all isolates being typed, therefore estimating the core-component of
the species becomes a subject of prime importance.
PMID- 25853709
TI - The impact of antipsychotic polytherapy costs in the public health care in Sao
Paulo, Brazil.
AB - INTRODUCTION: Guidelines for the treatment of psychoses recommend antipsychotic
monotherapy. However, the rate of antipsychotic polytherapy has increased over
the last decade, reaching up to 60% in some settings. Studies evaluating the
costs and impact of antipsychotic polytherapy in the health system are scarce.
OBJECTIVE: To estimate the costs of antipsychotic polytherapy and its impact on
public health costs in a sample of subjects with psychotic disorders living in
residential facilities in the city of Sao Paulo, Brazil. METHOD: A cross
sectional study that used a bottom-up approach for collecting costs data in a
public health provider's perspective. Subjects with psychosis living in 20 fully
staffed residential facilities in the city of Sao Paulo were assessed for
clinical and psychosocial profile, severity of symptoms, quality of life, use of
health services and pharmacological treatment. The impact of polytherapy on total
direct costs was evaluated. RESULTS: 147 subjects were included, 134 used
antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There
were no significant differences in clinical and psychosocial characteristics
between polytherapy and monotherapy groups. Four variables explained 30% of
direct costs: the number of antipsychotics, location of the residential facility,
time living in the facility and use of olanzapine. The costs of antipsychotics
corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health
services use when excluding accommodation costs. Olanzapine costs corresponded to
51% of all psychotropic costs. CONCLUSION: Antipsychotic polytherapy is a huge
economic burden to public health service, despite the lack of evidence supporting
this practice. Great variations on antipsychotic costs explicit the need of
establishing protocols for rational antipsychotic prescriptions and consequently
optimising resource allocation. Cost-effectiveness studies are necessary to
estimate the best value for money among antipsychotics, especially in low and
middle income countries.
PMID- 25853710
TI - Rectal application of a highly osmolar personal lubricant in a macaque model
induces acute cytotoxicity but does not increase risk of SHIV infection.
AB - BACKGROUND: Personal lubricant use is common during anal intercourse. Some water
based products with high osmolality and low pH can damage genital and rectal
tissues, and the polymer polyquaternium 15 (PQ15) can enhance HIV replication in
vitro. This has raised concerns that lubricants with such properties may increase
STD/HIV infection risk, although in vivo evidence is scarce. We use a macaque
model to evaluate rectal cytotoxicity and SHIV infection risk after use of a
highly osmolar (>8,000 mOsm/kg) water-based lubricant with pH of 4.4, and
containing PQ15. METHODS: Cytotoxicity was documented by measuring inflammatory
cytokines and epithelial tissue sloughing during six weeks of repeated, non
traumatic lubricant or control buffer applications to rectum and anus. We
measured susceptibility to SHIVSF162P3 infection by comparing virus doses needed
for rectal infection in twenty-one macaques treated with lubricant or control
buffer 30 minutes prior to virus exposure. RESULTS: Lubricant increased pro
inflammatory cytokines and tissue sloughing while control buffer (phosphate
buffered saline; PBS) did not. However, the estimated AID50 (50% animal
infectious dose) was not different in lubricant- and control buffer-treated
macaques (p = 0.4467; logistic regression models). CONCLUSIONS: Although the test
lubricant caused acute cytotoxicity in rectal tissues, it did not increase
susceptibility to infection in this macaque model. Thus neither the lubricant
induced type/extent of inflammation nor the presence of PQ15 affected infection
risk. This study constitutes a first step in the in vivo evaluation of lubricants
with regards to HIV transmission.
PMID- 25853711
TI - Snakes on the Balearic islands: an invasion tale with implications for native
biodiversity conservation.
AB - Biological invasions are a major conservation threat for biodiversity worldwide.
Islands are particularly vulnerable to invasive species, especially Mediterranean
islands which have suffered human pressure since ancient times. In the Balearic
archipelago, reptiles represent an outstanding case with more alien than native
species. Moreover, in the last decade a new wave of alien snakes landed in the
main islands of the archipelago, some of which were originally snake-free. The
identification of the origin and colonization pathways of alien species, as well
as the prediction of their expansion, is crucial to develop effective
conservation strategies. In this study, we used molecular markers to assess the
allochthonous status and the putative origin of the four introduced snake species
(Hemorrhois hippocrepis, Malpolon monspessulanus, Macroprotodon mauritanicus and
Rhinechis scalaris) as well as ecological niche models to infer their patterns of
invasion and expansion based on current and future habitat suitability. For most
species, DNA sequence data suggested the Iberian Peninsula as the potential
origin of the allochthonous populations, although the shallow phylogeographic
structure of these species prevented the identification of a restricted source
area. For all of them, the ecological niche models showed a current low habitat
suitability in the Balearic, which is however predicted to increase significantly
in the next few decades under climate change scenarios. Evidence from direct
observations and spatial distribution of the first-occurrence records of alien
snakes (but also lizards and worm lizards) suggest the nursery trade, and in
particular olive tree importation from Iberian Peninsula, as the main pathway of
introduction of alien reptiles in the Balearic islands. This trend has been
reported also for recent invasions in NE Spain, thus showing that olive trees
transplantation may be an effective vector for bioinvasion across the
Mediterranean. The combination of molecular and ecological tools used in this
study reveals a promising approach for the understanding of the complex invasion
process, hence guiding conservation management actions.
PMID- 25853712
TI - Charcoal reflectance reveals early holocene boreal deciduous forests burned at
high intensities.
AB - Wildfire size, frequency, and severity are increasing in the Alaskan boreal
forest in response to climate warming. One of the potential impacts of this
changing fire regime is the alteration of successional trajectories, from black
spruce to mixed stands dominated by aspen, a vegetation composition not
experienced since the early Holocene. Such changes in vegetation composition may
consequently alter the intensity of fires, influencing fire feedbacks to the
ecosystem. Paleorecords document past wildfire-vegetation dynamics and as such,
are imperative for our understanding of how these ecosystems will respond to
future climate warming. For the first time, we have used reflectance measurements
of macroscopic charcoal particles (>180MUm) from an Alaskan lake-sediment record
to estimate ancient charring temperatures (termed pyrolysis intensity). We
demonstrate that pyrolysis intensity increased markedly from an interval of birch
tundra 11 ky ago (mean 1.52%Ro; 485 degrees C), to the expansion of trees on the
landscape ~10.5 ky ago, remaining high to the present (mean 3.54%Ro; 640 degrees
C) irrespective of stand composition. Despite differing flammabilities and
adaptations to fire, the highest pyrolysis intensities derive from two intervals
with distinct vegetation compositions. 1) the expansion of mixed aspen and spruce
woodland at 10 cal. kyr BP, and 2) the establishment of black spruce, and the
modern boreal forest at 4 cal. kyr BP. Based on our analysis, we infer that
predicted expansion of deciduous trees into the boreal forest in the future could
lead to high intensity, but low severity fires, potentially moderating future
climate-fire feedbacks.
PMID- 25853713
TI - Interstitial fluid colloid osmotic pressure in healthy children.
AB - OBJECTIVE: The colloid osmotic pressure (COP) of plasma and interstitial fluid
play important roles in transvascular fluid exchange. COP values for monitoring
fluid balance in healthy and sick children have not been established. This study
set out to determine reference values of COP in healthy children. MATERIALS AND
METHODS: COP in plasma and interstitial fluid harvested from nylon wicks was
measured in 99 healthy children from 2 to 10 years of age. Nylon wicks were
implanted subcutaneously in arm and leg while patients were sedated and intubated
during a minor surgical procedure. COP was analyzed in a colloid osmometer
designed for small fluid samples. RESULTS: The mean plasma COP in all children
was 25.6 +/- 3.3 mmHg. Arbitrary division of children in four different age
groups, showed no significant difference in plasma or interstitial fluid COP
values for patients less than 8 years, whereas patients of 8-10 years had
significant higher COP both in plasma and interstitial fluid. There were no
gender difference or correlation between COP in interstitial fluid sampled from
arm and leg and no significant effect on interstitial COP of gravity. Prolonged
implantation time did not affect interstitial COP. CONCLUSION: Plasma and
interstitial COP in healthy children are comparable to adults and COP seems to
increase with age in children. Knowledge of the interaction between colloid
osmotic forces can be helpful in diseases associated with fluid imbalance and may
be crucial in deciding different fluid treatment options. TRIAL REGISTRATION:
ClinicalTrials.gov NCT01044641.
PMID- 25853714
TI - De novo RNA-Seq analysis of the venus clam, Cyclina sinensis, and the
identification of immune-related genes.
AB - The Venus clam, Cyclina sinensis, is one of the most important bivalves in China.
In recent years, increasing expansive morbidity has occurred in breeding areas,
imposing significant losses on the national economy. To understand the molecular
mechanisms of immune-related genes, we analyzed and sequenced hemolymph samples
that were injected with two pathogenic microorganisms using the Illumina Miseq
system. After trimming, more than 12 M PE reads with an average length greater
than 410 bp were assembled into 70,079 transcripts with a mean length of 980 bp.
Using a homology analysis, 102 (135 transcripts) potentially immune-related genes
were identified, and most of them exhibited a similar pattern in both samples.
These data indicated that the response of the clam to both types of bacterial
infection might follow a similar molecular mechanism. Using the TreeFam method,
9,904 gene families and 1,031 unique families of the clam were preliminarily
classified in comparison to five related species. A significant number of SSRs
were identified, which could facilitate the identification of polymorphisms in
Venus clam populations. These datasets will improve our knowledge of the
molecular mechanisms driving the immune response to bacterial infection in clam
populations and will provide basic data about clam breeding and disease control.
PMID- 25853716
TI - Peer effects in unethical behavior: standing or reputation?
AB - Recent empirical evidence shows that working in an unsupervised, isolated
situation under competition, can increase dishonest behavior to achieve prestige.
However, could working in a common space, in the presence of colleagues affect
cheating? Here, we examine how familiar-peer influence, supervision and social
incentives affect worker performance and dishonest behavior. First, we show that
working in the presence of peers is an effective mechanism to constrain
honest/dishonest behavior compared to an isolated work situation (experiment 1).
Second, we demonstrate that the mere suspicion of dishonesty from another peer is
not enough to affect individual cheating behavior (experiment 2), suggesting that
reputation holds great importance in a worker's self-image acting as a strong
social incentives. Third, we show that when the suspicion of dishonesty increases
with multiple peers behaving dishonestly, the desire to increase standing is
sufficient to nudge individuals' behavior back to cheating at the same levels as
isolated situations (experiment 3).
PMID- 25853717
TI - Multidimensional determinants of family caregiver burden in Alzheimer's disease.
AB - BACKGROUND: Caregiver burden is a complex and multidimensional construct.
Although previous studies have explored numerous factors associated with
caregiver burden, these factors have not been identified with a large population
based sample in a theory-based multidimensional way. This study explores
multidimensional determinants associated with family caregiver burden to
determine the main contributors of caregiver burden in Alzheimer's disease (AD)
using a large community dataset. METHODS: A retrospective secondary data analysis
was conducted on 1,133 patients with AD and 1,133 primary caregivers who were
registered in a metropolitan city dementia center in South Korea. The patient
data included socio-demographic and disease profiles. The caregiver data
consisted of socio-demographic and caregiving profiles. RESULTS: The study
results identified that dementia-related factors were the most significant
factors, representing 25.6% of caregiver burden and were followed by caregiving
related factors explaining caregiver burden significantly. Behavioral problems
and instrumental activities of daily living (IADL) dependency of the patient,
spousal relationship, hours of caregiving, and the number of diseases associated
with the caregiver were found to be significant individual variables.
CONCLUSIONS: It is vital to develop a service and support program with a greater
emphasis on the behavioral problems and IADL deficiency of patients with AD as
well as on improving the competence ability of caregivers to deal with such
difficulties.
PMID- 25853718
TI - How Parents' Lack of Awareness Could Be Associated With Foreign Body Aspiration
in Children.
AB - Foreign body aspiration (FBA) in preschool children is a worldwide challenging
clinical problem that can result in life-threatening complications. Three cases
of FBA in preschool children are presented. All the children were admitted to the
hospital with asthma-like symptoms, without any aspiration history. Although FBA
was considered in differential diagnosis, there was no strong evidence to support
this diagnosis. The persistence of symptoms despite the appropriate treatment for
the asthma symptoms was the main reason for the reconsideration of FBA. All of
the children underwent bronchoscopy, with the successful removal of small organic
food items from the main bronchi. The main cause of FBA was the parents' lack of
awareness concerning the risk of FBA when small organic food items are provided
to preschool children. These cases demonstrate that some parents are unfamiliar
with the risk of FBA when small organic food items are provided to their
children. It is crucial to make it understood that consideration of FBA should be
maintained throughout the clinical course of patients with an acute onset of
respiratory symptoms, despite the initial lack of evidence to support this
diagnosis, and that parental education about the causes and hazards of this
condition may be the best preventive measure to decrease its incidence.
PMID- 25853719
TI - Fainting Starting Parenteral Nutrition.
AB - Complications such as mechanical accidents, infections, and thrombosis are
commonly described in the presence of a central venous catheter. We present a
case of a boy who had fainting episodes due to dislocation of a central venous
catheter.
PMID- 25853720
TI - Extraocular cranial nerve palsies in children.
AB - Visual disturbances resulting from acute nerve paralysis of the muscles
controlling eye movements can be challenging to evaluate in the pediatric
population. Children may not be capable of describing symptoms or providing an
adequate history. Therefore, it is important to have an understanding of the
anatomical course of the extraocular cranial nerves and clinical manifestations
of their dysfunction. We report 2 cases of extraocular cranial nerve palsies and,
in addition to an anatomical review, discuss the common etiologies of paralysis
and the importance of ophthalmological and neurological follow-up to ensure
optimal long-term visual function.
PMID- 25853721
TI - Where Is the Air Coming From? A Case Report of an Adolescent With Cervicofacial
Emphysema.
AB - Cervicofacial subcutaneous emphysema is uncommon in children and adolescents.
When it occurs, it is often a result of trauma, surgery, or complication of
pneumomediastinum. We report a case of an adolescent with isolated cervicofacial
emphysema likely from an ulcer in his buccal mucosa.
PMID- 25853722
TI - Status Epilepticus Due to Cat Scratch Disease: Recognition, Diagnosis, and
Thoughts on Pathogenesis.
AB - Despite the publication of a number of case reports since the 1950s, physician
awareness of the unique relationship between cat scratch disease (CSD) and acute
encephalopathy remains limited. This report alerts emergency medicine physicians
to include CSD encephalopathy (CSDE) in the differential diagnosis when a
previously healthy child presents with status epilepticus. Prompt recognition of
this relationship impacts the selection of initial diagnostic studies and
antibiotic choices and permits reliable insight into prognosis. The 2 cases are
from different eras and demonstrate the significant diagnostic advances in the
past 3 decades for Bartonella henselae infection. Both children were treated with
antibiotics, and both had resolution of all neurological symptoms. However, the
role of antibiotics in the treatment and outcome of CSDE remains speculative.
Lastly, the report suggests potential areas of investigation to address immune
mediated mechanisms in the pathogenesis of CSDE.
PMID- 25853723
TI - Cephalic Tetanus in an Immunized Teenager: An Unusual Case Report.
AB - Tetanus is a rare disease in developed countries but is prevalent worldwide. It
has significant morbidity and mortality. The causative agent Clostridium tetani
is ubiquitous in nature. In the United States, approximately 50 to 100 cases are
reported per year but rarely in immunocompetent, fully immunized patients. Of the
four types of tetanus (generalized, neonatal, cephalic, and localized), cephalic
is the least common. We present a case of cephalic tetanus in a 14-year-old boy
who completed his primary immunizations with a video of his physical examination
findings.
PMID- 25853724
TI - Three-dimensional surface-enhanced Raman scattering hotspots in spherical
colloidal superstructure for identification and detection of drugs in human
urine.
AB - Rapid component separation and robust surface-enhanced Raman scattering (SERS)
identification of drugs in real human urine remain an attractive challenge
because of the sample complexity, low molecular affinity for metal surface, and
inefficient use of hotspots in one- or two-dimensional (2D) geometries. Here, we
developed a 5 min strategy of cyclohexane (CYH) extraction for separating
amphetamines from human urine. Simultaneously, an oil-in-water emulsion method is
used to assemble monodisperse Ag nanoparticles in the CYH phase into spherical
colloidal superstructures in the aqueous phase. These superstructures create
three-dimensional (3D) SERS hotspots which exist between every two adjacent
particles in 3D space, break the traditional 2D limitation, and extend the
hotspots into the third dimension along the z-axis. In this platform, a
conservative estimate of Raman enhancement factor is larger than 10(7), and the
same CYH extraction processing results in a high acceptability and enrichment of
drug molecules in 3D hotspots which demonstrates excellent stability and
reproducibility and is suitable for the quantitative examination of amphetamines
in both aqueous and organic phases. Parallel ultraperformance liquid
chromatography (UPLC) examinations corroborate an excellent performance of our
SERS platform for the quantitative analysis of methamphetamine (MA) in both
aqueous solution and real human urine, of which the detection limits reach 1 and
10 ppb, respectively, with tolerable signal-to-noise ratios. Moreover, SERS
examinations on different proportions of MA and 3,4-methylenedioxymethamphetamine
(MDMA) in human urine demonstrate an excellent capability of multiplex
quantification of ultratrace analytes. By virtue of a spectral classification
algorithm, we realize the rapid and accurate recognition of weak Raman signals of
amphetamines at trace levels and also clearly distinguish various proportions of
multiplex components. Our platform for detecting drugs promises to be a great
prospect for a rapid, reliable, and on-spot analyzer.
PMID- 25853725
TI - Opioid use in the management of diabetic peripheral neuropathy (DPN) in a large
commercially insured population.
AB - OBJECTIVE: To examine the proportion of diabetic peripheral neuropathy (DPN)
patients receiving pharmacologic DPN treatments and specifically to identify the
rates and factors associated with opioid use and first-line opioid use. METHODS:
A 10% sample of IMS-LifeLink claims data from 1998 through 2008 was used. The
study population consisted of diabetic patients who met DPN criteria using a
validated DPN algorithm. Multivariable logistic regression controlling for
demographics, comorbidities, and other clinical characteristics was used to
identify factors associated with any DPN pharmacologic treatment, any opioid use,
and first-line opioid treatment. Sensitivity analyses were conducted to explore
variations in exclusion criteria as well as opioid use definitions. RESULTS: A
total of 666 DPN patients met inclusion criteria and pharmacologic treatment was
received by 288 patients (43.24%) and of those, 154 (53.47%) had DPN-related
opioid use and 96 (33.33%) received opioid as first-line treatment. Persons with
diabetic complications were more likely to use opioids (odds ratio=4.53; 95%
confidence interval, 1.09-18.92). Food and Drug Administration-approved DPN
agents duloxetine 1.04% (n=3) and pregabalin 5.56% (n=16) had much lower rates of
use. DPN-related drug use and DPN-related opioid usage increased as we used less
restrictive samples in sensitivity analyses. CONCLUSIONS: Opioids were the most
frequently prescribed first-line agents for DPN. More than 50% of DPN patients
remained untreated with pharmacologic agents 1 year after a DPN diagnosis.
PMID- 25853727
TI - Correction: The pH-responsive PacC transcription factor of Aspergillus fumigatus
governs epithelial entry and tissue invasion during pulmonary aspergillosis.
AB - [This corrects the article DOI: 10.1371/journal.ppat.1004413.].
PMID- 25853726
TI - Phosphorylation of mutationally introduced tyrosine in the activation loop of
HER2 confers gain-of-function activity.
AB - Amplification, overexpression, and somatic mutation of the HER2 gene have been
reported to play a critical role in tumorigenesis of various cancers. The HER2
H878Y mutation was recently reported in 11% of hepatocellular carcinoma (HCC)
patients. However, its functional impact on the HER2 protein and its role in
tumorigenesis has not been determined. Here, we show that HER2 H878Y is a gain-of
function mutation. Y878 represents a phosphorylation site, and phospho-Y878
interacts with R898 residue to stabilize the active conformation of HER2, thereby
enhancing its kinase activity. H878Y mutant is transforming and the transformed
cells are sensitive to HER2 kinase inhibitors. Thus, our study reveals the
following novel mechanism underlying the tumorigenic function of the HER2 H878Y
mutation: the introduction of a tyrosine residue into the kinase activation loop
via mutagenesis modulates the conformation of the kinase, thereby enhancing its
activity.
PMID- 25853728
TI - Effect of resource spatial correlation and hunter-fisher-gatherer mobility on
social cooperation in Tierra del Fuego.
AB - This article presents an agent-based model designed to explore the development of
cooperation in hunter-fisher-gatherer societies that face a dilemma of sharing an
unpredictable resource that is randomly distributed in space. The model is a
stylised abstraction of the Yamana society, which inhabited the channels and
islands of the southernmost part of Tierra del Fuego (Argentina-Chile). According
to ethnographic sources, the Yamana developed cooperative behaviour supported by
an indirect reciprocity mechanism: whenever someone found an extraordinary
confluence of resources, such as a beached whale, they would use smoke signals to
announce their find, bringing people together to share food and exchange
different types of social capital. The model provides insight on how the spatial
concentration of beachings and agents' movements in the space can influence
cooperation. We conclude that the emergence of informal and dynamic communities
that operate as a vigilance network preserves cooperation and makes defection
very costly.
PMID- 25853730
TI - Correction to "Catalytic Mechanism of Hyaluronate Lyase from Streptococcus
pneumoniae: Quantum Mechanical/Molecular Mechanical and Density Functional Theory
Studies".
PMID- 25853731
TI - Biopatterning of Silk Proteins for Soft Micro-optics.
AB - Silk proteins from spiders and silkworms have been proposed as outstanding
candidates for soft micro-optic and photonic applications because of their
optical transparency, unique biological properties, and mechanical robustness.
Here, we present a method to form microstructures of the two constituent silk
proteins, fibroin and sericin for use as an optical biomaterial. Using
photolithography, chemically modified silk protein photoresists are patterned in
2D arrays of periodic patterns and Fresnel zone plates. Angle-dependent
iridescent colors are produced in these periodic micropatterns because of the
Bragg diffraction. Silk protein photolithography can used to form patterns on
different substrates including flexible sheets with features of any shape with
high fidelity and resolution over large areas. Finally, we show that these
mechanically stable and transparent iridescent architectures are also completely
biodegradable. This versatile and scalable technique can therefore be used to
develop biocompatible, soft micro-optic devices that can be degraded in a
controlled manner.
PMID- 25853729
TI - Time, monetary and other costs of participation in family-based child weight
management interventions: qualitative and systematic review evidence.
AB - BACKGROUND: Childhood overweight and obesity have health and economic impacts on
individuals and the wider society. Families participating in weight management
programmes may foresee or experience monetary and other costs which deter them
from signing up to or completing programmes. This is recognised in the health
economics literature, though within this sparse body of work, costs to families
are often narrowly defined and not fully accounted for. A societal perspective
incorporating a broader array of costs may provide a more accurate picture. This
paper brings together a review of the health economics literature on the costs to
families attending child weight management programmes with qualitative data from
families participating in a programme to manage child overweight and obesity.
METHODS: A search identified economic evaluation studies of lifestyle
interventions in childhood obesity. The qualitative work drew on interviews with
families who attended a weight management intervention in three UK regions.
RESULTS: We identified four cost-effectiveness analyses that include information
on costs to families. These were categorised as direct (e.g. monetary) and
indirect (e.g. time) costs. Our analysis of qualitative data demonstrated that,
for families who attended the programme, costs were associated both with
participation on the scheme and with maintaining a healthy lifestyle afterwards.
Respondents reported three kinds of cost: time-related, social/emotional and
monetary. CONCLUSION: Societal approaches to measuring cost-effectiveness provide
a framework for assessing the monetary and non-monetary costs borne by
participants attending treatment programmes. From this perspective, all costs
should be considered in any analysis of cost-effectiveness. Our data suggest that
family costs are important, and may act as a barrier to the uptake, completion
and maintenance of behaviours to reduce child obesity. These findings have
implications for the development and implementation of child weight initiatives
in particular, in relation to reducing inequalities in health.
PMID- 25853732
TI - Small RNA in the acid tolerance response of Salmonella and their role in
virulence.
PMID- 25853733
TI - Comparative virulence of urinary and bloodstream isolates of extra-intestinal
pathogenic Escherichia coli in a Galleria mellonella model.
AB - Extra-intestinal pathogenic Escherichia coli (ExPEC) are a significant cause of
urinary tract infections and bacteraemia worldwide. Currently no single virulence
factor or ExPEC lineage has been identified as the sole contributor to severe
extra-intestinal infection and/or urosepsis. Galleria mellonella has recently
been established as a simple model for studying the comparative virulence of
ExPEC. In this study we investigated the virulence of 40 well-characterized ExPEC
strains, in G. mellonella, by measuring mortality (larvae survival), immune
recognition/response (melanin production) and cell damage (lactate dehydrogenase
production). Although mortality was similar between urinary and bloodstream
isolates, it was heightened for community-associated infections, complicated UTIs
and urinary-source bacteraemia. Isolates of ST131 and those possessing afa/dra,
ompT and serogroup O6 were also associated with heightened virulence.
PMID- 25853734
TI - Peptides for specifically targeting nanoparticles to cellular organelles: quo
vadis?
AB - The interfacing of nanomaterials and especially nanoparticles within all aspects
of biological research continues to grow at a nearly unabated pace with projected
applications focusing on powerful new tools for cellular labeling, imaging, and
sensing, theranostic materials, and drug delivery. At the most fundamental level,
many of these nanoparticles are meant to target not only very specific cell
types, regardless of whether they are in a culture, tissue, an animal model, or
ultimately a patient, but also in many cases a specific subcellular organelle.
During this process, these materials will undergo a complex journey that must
first find the target cell of interest, then be taken up by those cells across
the extracellular membrane, and ultimately localize to a desired subcellular
organelle, which may include the nucleus, plasma membrane, endolysosomal system,
mitochondria, cytosol, or endoplasmic reticulum. To accomplish these complex
tasks in the correct sequence, researchers are increasingly interested in
selecting for and exploiting targeting peptides that can impart the requisite
capabilities to a given nanoparticle construct. There are also a number of
related criteria that need careful consideration for this undertaking centering
on the nature and properties of the peptide vector itself, the peptide
nanoparticle conjugate characteristics, and the target cell. Here, we highlight
some important issues and key research areas related to this burgeoning field. We
begin by providing a brief overview of some criteria for optimal attachment of
peptides to nanoparticles, the predominant methods by which nanoparticles enter
cells, and some of the peptide sequences that have been utilized to facilitate
nanoparticle delivery to cells focusing on those that engender the initial
targeting and uptake. Because almost all materials delivered to cells by peptides
utilize the endosomal system of vesicular transport and in many cases remain
sequestered within the vesicles, we critically evaluate the issue of endosomal
escape in the context of some recently reported successes in this regard.
Following from this, peptides that have been reported to deliver nanoparticles to
specific subcellular compartments are examined with a focus on what they
delivered and the putative mechanisms by which they were able to accomplish this.
The last section focuses on two areas that are critical to realizing this overall
approach in the long term. The first is how to select for peptidyl sequences
capable of improved or more specific cellular or subcellular targeting based upon
principles commonly associated with drug discovery. The second looks at what has
been done to create modular peptides that incorporate multiple desirable
functionalities within a single, contiguous sequence. This provides a viable
alternative to either the almost insurmountable challenge of finding one sequence
capable of all functions or, alternatively, attaching different peptides with
different functionalities to the same nanoparticle in different ratios when
trying to orchestrate their net effects. Finally, we conclude with a brief
perspective on the future evolution and broader impact of this growing area of
bionanoscience.
PMID- 25853736
TI - Comparison of Two Available RNA Extraction Protocols for microRNA Amplification
in Serum Samples.
AB - BACKGROUND: microRNAs play a critical role in many biological processes such as
cell proliferation and maturation, apoptosis, regulation of chronic inflammation
and development of cancer. METHODS: In this study is described a protocol for the
isolation of RNA from serum and subsequent determination of miRNA expression
levels using TaqMan-based MGB Real-Time PCR detection. RNA was extracted using
two different isolation methods including available kits RNAzol and a modified
RNAzol protocol. In all cases, RNA was eluted in RNase free H2 O, kept frozen
until analysis and the presence of contaminants assessed by NanoDrop
spectrophotometry. RESULTS: Higher RNA quantity was observed in RNAzol (378.8
ng/MUl) vs RNAzol modified protocol (226.5 ng/MUl) and a better performance in
terms of RNA extraction yield and purity. Subsequently, measurements of
endogenous miRNAs (RNU43), cellular miRNAs (mir155 and mir146a) and EBV miRNAs
(mirBART2-5p, mirBART15 and mirBART22) were performed by RT-qPCR. CONCLUSION: In
contrast to the findings in terms of purity and quantity, the amplifiable RNA was
more abundant using RNAzol modified protocol compared to not modified protocol.
PMID- 25853735
TI - Advanced echocardiography in adult zebrafish reveals delayed recovery of heart
function after myocardial cryoinjury.
AB - Translucent zebrafish larvae represent an established model to analyze genetics
of cardiac development and human cardiac disease. More recently adult zebrafish
are utilized to evaluate mechanisms of cardiac regeneration and by benefiting
from recent genome editing technologies, including TALEN and CRISPR, adult
zebrafish are emerging as a valuable in vivo model to evaluate novel disease
genes and specifically validate disease causing mutations and their underlying
pathomechanisms. However, methods to sensitively and non-invasively assess
cardiac morphology and performance in adult zebrafish are still limited. We here
present a standardized examination protocol to broadly assess cardiac performance
in adult zebrafish by advancing conventional echocardiography with modern speckle
tracking analyses. This allows accurate detection of changes in cardiac
performance and further enables highly sensitive assessment of regional
myocardial motion and deformation in high spatio-temporal resolution. Combining
conventional echocardiography measurements with radial and longitudinal velocity,
displacement, strain, strain rate and myocardial wall delay rates after
myocardial cryoinjury permitted to non-invasively determine injury dimensions and
to longitudinally follow functional recovery during cardiac regeneration. We show
that functional recovery of cryoinjured hearts occurs in three distinct phases.
Importantly, the regeneration process after cryoinjury extends far beyond the
proposed 45 days described for ventricular resection with reconstitution of
myocardial performance up to 180 days post-injury (dpi). The imaging modalities
evaluated here allow sensitive cardiac phenotyping and contribute to further
establish adult zebrafish as valuable cardiac disease model beyond the larval
developmental stage.
PMID- 25853737
TI - Disputing Lamarckian epigenetic inheritance in mammals.
AB - A recent study finds that changes to transcription and DNA methylation resulting
from in utero exposure to environmental endocrine-disrupting chemicals are not
inherited across generations.
PMID- 25853738
TI - Lancet dynamics in greater horseshoe bats, Rhinolophus ferrumequinum.
AB - Echolocating greater horseshoe bats (Rhinolophus ferrumequinum) emit their
biosonar pulses nasally, through nostrils surrounded by fleshy appendages
('noseleaves') that diffract the outgoing ultrasonic waves. Movements of one
noseleaf part, the lancet, were measured in live bats using two synchronized high
speed video cameras with 3D stereo reconstruction, and synchronized with pulse
emissions recorded by an ultrasonic microphone. During individual broadcasts, the
lancet briefly flicks forward (flexion) and is then restored to its original
position. This forward motion lasts tens of milliseconds and increases the
curvature of the affected noseleaf surfaces. Approximately 90% of the maximum
displacements occurred within the duration of individual pulses, with 70%
occurring towards the end. Similar lancet motions were not observed between
individual pulses in a sequence of broadcasts. Velocities of the lancet motion
were too small to induce Doppler shifts of a biologically-meaningful magnitude,
but the maximum displacements were significant in comparison with the overall
size of the lancet and the ultrasonic wavelengths. Three finite element models
were made from micro-CT scans of the noseleaf post mortem to investigate the
acoustic effects of lancet displacement. The broadcast beam shapes were found to
be altered substantially by the observed small lancet movements. These findings
demonstrate that-in addition to the previously described motions of the anterior
leaf and the pinna-horseshoe bat biosonar has a third degree of freedom for fast
changes that can happen on the time scale of the emitted pulses or the returning
echoes and could provide a dynamic mechanism for the encoding of sensory
information.
PMID- 25853739
TI - Expanding the forefront of strong organic Bronsted acids: proton-catalyzed
hydroamination of unactivated alkenes and activation of Au(I) for alkyne
hydroamination.
AB - The synthesis of a solid, bench-stable, strong organic Bronsted acid with a
computed pKa of 0.9 is reported. An X-ray crystal structure and DFT calculations
are provided which offer insight into the bonding of this acid. The application
of this strong organic Bronsted acid as a catalyst for the intermolecular
hydroamination of unactivated alkenes and as an activator for Au(I)-catalyzed
alkyne hydroamination with anilines is described.
PMID- 25853740
TI - Probing the Limits of Conventional Extended X-ray Absorption Fine Structure
Analysis Using Thiolated Gold Nanoparticles.
AB - We present a method for quantifying the accuracy of extended X-ray absorption
fine structure (EXAFS) fitting models. As a test system, we consider the
structure of bare Au147 nanoparticles as well as particles bound with thiol
ligands, which are used to systematically vary disorder in the atomic structure
of the nanoparticles. The accuracy of the fitting model is determined by
comparing two distributions of bond lengths: (1) a direct average over a
molecular dynamics (MD) trajectory using forces and energies from density
functional theory (DFT) and (2) a fit to the theoretical EXAFS spectra generated
from that same trajectory. Both harmonic and quasi-harmonic EXAFS fitting models
are used to characterize the first-shell Au-Au bond length distribution. The
harmonic model is found to significantly underestimate the coordination number,
disorder, and bond length. The quasi-harmonic model, which includes the third
cumulant of the first-shell bond length distribution, yields accurate bond
lengths, but incorrectly predicts a decrease in particle size and little change
in the disorder with increasing thiol ligands. A direct analysis of the MD data
shows that the particle surfaces become much more disordered with ligand binding,
and the high disorder is incorrectly interpreted by the EXAFS fitting models. Our
DFT calculations compare well with experimental EXAFS measurements of Au
nanoparticles, synthesized using a dendrimer encapsulation technique, showing
that systematic errors in EXAFS fitting models apply to nanoparticles 1-2 nm in
size. Finally we show that a combination of experimental EXAFS analysis with
candidate models from DFT is a promising strategy for a more accurate
determination of nanoparticle structures.
PMID- 25853741
TI - The next epidemic--lessons from Ebola.
PMID- 25853742
TI - Medicare's step back from global payments--unbundling postoperative care.
PMID- 25853743
TI - Randomized trial of primary PCI with or without routine manual thrombectomy.
AB - BACKGROUND: During primary percutaneous coronary intervention (PCI), manual
thrombectomy may reduce distal embolization and thus improve microvascular
perfusion. Small trials have suggested that thrombectomy improves surrogate and
clinical outcomes, but a larger trial has reported conflicting results. METHODS:
We randomly assigned 10,732 patients with ST-segment elevation myocardial
infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual
thrombectomy versus PCI alone. The primary outcome was a composite of death from
cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New
York Heart Association (NYHA) class IV heart failure within 180 days. The key
safety outcome was stroke within 30 days. RESULTS: The primary outcome occurred
in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030
patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group,
0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of
cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard
ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent
thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00;
95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred
in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the
PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). CONCLUSIONS:
In patients with STEMI who were undergoing primary PCI, routine manual
thrombectomy, as compared with PCI alone, did not reduce the risk of
cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA
class IV heart failure within 180 days but was associated with an increased rate
of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of
Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).
PMID- 25853746
TI - Effects of red-cell storage duration on patients undergoing cardiac surgery.
AB - BACKGROUND: Some observational studies have reported that transfusion of red-cell
units that have been stored for more than 2 to 3 weeks is associated with
serious, even fatal, adverse events. Patients undergoing cardiac surgery may be
especially vulnerable to the adverse effects of transfusion. METHODS: We
conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12
years of age or older who were undergoing complex cardiac surgery and were likely
to undergo transfusion of red cells were randomly assigned to receive leukocyte
reduced red cells stored for 10 days or less (shorter-term storage group) or for
21 days or more (longer-term storage group) for all intraoperative and
postoperative transfusions. The primary outcome was the change in Multiple Organ
Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more
severe organ dysfunction) from the preoperative score to the highest composite
score through day 7 or the time of death or discharge. RESULTS: The median
storage time of red-cell units provided to the 1098 participants who received red
cell transfusion was 7 days in the shorter-term storage group and 28 days in the
longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7
points, respectively (95% confidence interval for the difference, -0.6 to 0.3;
P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0%
in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%,
respectively (P=0.57). Adverse events did not differ significantly between groups
except that hyperbilirubinemia was more common in the longer-term storage group.
CONCLUSIONS: The duration of red-cell storage was not associated with significant
differences in the change in MODS. We did not find that the transfusion of red
cells stored for 10 days or less was superior to the transfusion of red cells
stored for 21 days or more among patients 12 years of age or older who were
undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and
Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).
PMID- 25853747
TI - Ibrutinib in previously treated Waldenstrom's macroglobulinemia.
AB - BACKGROUND: MYD88(L265P) and CXCR4(WHIM) mutations are highly prevalent in
Waldenstrom's macroglobulinemia. MYD88(L265P) triggers tumor-cell growth through
Bruton's tyrosine kinase, a target of ibrutinib. CXCR4(WHIM) mutations confer in
vitro resistance to ibrutinib. METHODS: We performed a prospective study of
ibrutinib in 63 symptomatic patients with Waldenstrom's macroglobulinemia who had
received at least one previous treatment, and we investigated the effect of MYD88
and CXCR4 mutations on outcomes. Ibrutinib at a daily dose of 420 mg was
administered orally until disease progression or the development of unacceptable
toxic effects. RESULTS: After the patients received ibrutinib, median serum IgM
levels decreased from 3520 mg per deciliter to 880 mg per deciliter, median
hemoglobin levels increased from 10.5 g per deciliter to 13.8 g per deciliter,
and bone marrow involvement decreased from 60% to 25% (P<0.01 for all
comparisons). The median time to at least a minor response was 4 weeks. The
overall response rate was 90.5%, and the major response rate was 73.0%; these
rates were highest among patients with MYD88(L265P)CXCR4(WT) (with WT indicating
wild-type) (100% overall response rate and 91.2% major response rate), followed
by patients with MYD88(L265P)CXCR4(WHIM) (85.7% and 61.9%, respectively) and
patients with MYD88(WT)CXCR4(WT) (71.4% and 28.6%). The estimated 2-year
progression-free and overall survival rates among all patients were 69.1% and
95.2%, respectively. Treatment-related toxic effects of grade 2 or higher
included neutropenia (in 22% of the patients) and thrombocytopenia (in 14%),
which were more common in heavily pretreated patients; postprocedural bleeding
(in 3%); epistaxis associated with the use of fish-oil supplements (in 3%); and
atrial fibrillation associated with a history of arrhythmia (5%). CONCLUSIONS:
Ibrutinib was highly active, associated with durable responses, and safe in
pretreated patients with Waldenstrom's macroglobulinemia. MYD88 and CXCR4
mutation status affected responses to this drug. (Funded by Pharmacyclics and
others; ClinicalTrials.gov number, NCT01614821.).
PMID- 25853744
TI - Surgical ablation of atrial fibrillation during mitral-valve surgery.
AB - BACKGROUND: Among patients undergoing mitral-valve surgery, 30 to 50% present
with atrial fibrillation, which is associated with reduced survival and increased
risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted,
but evidence regarding its safety and effectiveness is limited. METHODS: We
randomly assigned 260 patients with persistent or long-standing persistent atrial
fibrillation who required mitral-valve surgery to undergo either surgical
ablation (ablation group) or no ablation (control group) during the mitral-valve
operation. Patients in the ablation group underwent further randomization to
pulmonary-vein isolation or a biatrial maze procedure. All patients underwent
closure of the left atrial appendage. The primary end point was freedom from
atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day
Holter monitoring). RESULTS: More patients in the ablation group than in the
control group were free from atrial fibrillation at both 6 and 12 months (63.2%
vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom
from atrial fibrillation between patients who underwent pulmonary-vein isolation
and those who underwent the biatrial maze procedure (61.0% and 66.0%,
respectively; P=0.60). One-year mortality was 6.8% in the ablation group and 8.7%
in the control group (hazard ratio with ablation, 0.76; 95% confidence interval,
0.32 to 1.84; P=0.55). Ablation was associated with more implantations of a
permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years,
P=0.01). There were no significant between-group differences in major cardiac or
cerebrovascular adverse events, overall serious adverse events, or hospital
readmissions. CONCLUSIONS: The addition of atrial fibrillation ablation to mitral
valve surgery significantly increased the rate of freedom from atrial
fibrillation at 1 year among patients with persistent or long-standing persistent
atrial fibrillation, but the risk of implantation of a permanent pacemaker was
also increased. (Funded by the National Institutes of Health and the Canadian
Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.).
PMID- 25853748
TI - Cancers complicating inflammatory bowel disease.
PMID- 25853749
TI - Images in clinical medicine. Incisional keloid.
PMID- 25853750
TI - Case records of the Massachusetts General Hospital. Case 11-2015. A 28-year-old
woman with headache, fever, and a rash.
PMID- 25853751
TI - Coronary microvascular obstruction--a puzzle with many pieces.
PMID- 25853752
TI - Surgical ablation of atrial fibrillation--when, why, and how?
PMID- 25853753
TI - Gestational hypertension and preeclampsia in living kidney donors.
PMID- 25853754
TI - Gestational hypertension and preeclampsia in living kidney donors.
PMID- 25853755
TI - Gestational hypertension and preeclampsia in living kidney donors.
PMID- 25853756
TI - Gestational hypertension and preeclampsia in living kidney donors.
PMID- 25853745
TI - Age of transfused blood in critically ill adults.
AB - BACKGROUND: Fresh red cells may improve outcomes in critically ill patients by
enhancing oxygen delivery while minimizing the risks of toxic effects from
cellular changes and the accumulation of bioactive materials in blood components
during prolonged storage. METHODS: In this multicenter, randomized, blinded
trial, we assigned critically ill adults to receive either red cells that had
been stored for less than 8 days or standard-issue red cells (the oldest
compatible units available in the blood bank). The primary outcome measure was 90
day mortality. RESULTS: Between March 2009 and May 2014, at 64 centers in Canada
and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood
group) and 1219 patients were assigned to receive standard-issue red cells
(standard-blood group). Red cells were stored a mean (+/-SD) of 6.1+/-4.9 days in
the fresh-blood group as compared with 22.0+/-8.4 days in the standard-blood
group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and
430 patients (35.3%) in the standard-blood group had died (absolute risk
difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In
the survival analysis, the hazard ratio for death in the fresh-blood group, as
compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38).
There were no significant between-group differences in any of the secondary
outcomes (major illnesses; duration of respiratory, hemodynamic, or renal
support; length of stay in the hospital; and transfusion reactions) or in the
subgroup analyses. CONCLUSIONS: Transfusion of fresh red cells, as compared with
standard-issue red cells, did not decrease the 90-day mortality among critically
ill adults. (Funded by the Canadian Institutes of Health Research and others;
Current Controlled Trials number, ISRCTN44878718.).
PMID- 25853757
TI - Esophageal carcinoma.
PMID- 25853758
TI - Esophageal carcinoma.
PMID- 25853759
TI - Esophageal carcinoma.
PMID- 25853760
TI - Esophageal carcinoma.
PMID- 25853761
TI - Esophageal carcinoma.
PMID- 25853762
TI - Expanded access to investigational drugs.
PMID- 25853763
TI - Expanded access to investigational drugs.
PMID- 25853764
TI - PML in a patient without severe lymphocytopenia receiving dimethyl fumarate.
PMID- 25853765
TI - PML in a patient with lymphocytopenia treated with dimethyl fumarate.
PMID- 25853766
TI - Case 26-2014: A 21-month-old boy with lethargy, respiratory distress, and
abdominal distention.
PMID- 25853767
TI - Long-term efficacy of a hepatitis E vaccine.
PMID- 25853768
TI - Images in clinical medicine. Epiglottitis in an adult.
PMID- 25853769
TI - Interactive medical case. A man with diarrhea and back pain.
PMID- 25853771
TI - Asymmetric Dearomatization of Naphthols via a Rh-Catalyzed C(sp2)-H
Functionalization/Annulation Reaction.
AB - A Rh-catalyzed enantioselective dearomatization of 1-aryl-2-naphthols with
internal alkynes via C-H functionalization reaction was achieved. In the presence
of a chiral Cp/Rh catalyst and combined oxidants of Cu(OAc)2 and air (oxygen),
various highly enantioenriched spirocyclic enones bearing an all-carbon
quaternary stereogenic center could be synthesized in 33-98% yields with up to
97:3 er.
PMID- 25853770
TI - MK3 modulation affects BMI1-dependent and independent cell cycle check-points.
AB - Although the MK3 gene was originally found deleted in some cancers, it is highly
expressed in others. The relevance of MK3 for oncogenesis is currently not clear.
We recently reported that MK3 controls ERK activity via a negative feedback
mechanism. This prompted us to investigate a potential role for MK3 in cell
proliferation. We here show that overexpression of MK3 induces a proliferative
arrest in normal diploid human fibroblasts, characterized by enhanced expression
of replication stress- and senescence-associated markers. Surprisingly, MK3
depletion evokes similar senescence characteristics in the fibroblast model. We
previously identified MK3 as a binding partner of Polycomb Repressive Complex 1
(PRC1) proteins. In the current study we show that MK3 overexpression results in
reduced cellular EZH2 levels and concomitant loss of epigenetic H3K27me3-marking
and PRC1/chromatin-occupation at the CDKN2A/INK4A locus. In agreement with this,
the PRC1 oncoprotein BMI1, but not the PCR2 protein EZH2, bypasses MK3-induced
senescence in fibroblasts and suppresses P16INK4A expression. In contrast, BMI1
does not rescue the MK3 loss-of-function phenotype, suggesting the involvement of
multiple different checkpoints in gain and loss of MK3 function. Notably, MK3
ablation enhances proliferation in two different cancer cells. Finally, the
fibroblast model was used to evaluate the effect of potential tumorigenic MK3
driver-mutations on cell proliferation and M/SAPK signaling imbalance. Taken
together, our findings support a role for MK3 in control of proliferation and
replicative life-span, in part through concerted action with BMI1, and suggest
that the effect of MK3 modulation or mutation on M/SAPK signaling and,
ultimately, proliferation, is cell context-dependent.
PMID- 25853772
TI - Comparison of hybrid constructs with 2-level artificial disc replacement and 2
level anterior cervical discectomy and fusion for surgical reconstruction of the
cervical spine: a kinematic study in whole cadavers.
AB - BACKGROUND: Multi-level cervical degeneration of the spine is a common clinical
pathology that is often repaired by anterior cervical discectomy and fusion
(ACDF). The aim of this study was to investigate the kinematics of the cervical
spine after hybrid surgery compared with 2-level ACDF. MATERIAL AND METHODS: Five
freshly frozen, unembalmed whole human cadavers were used including 3 males and 2
females with a mean age of 51 +/- 8 years. After evaluating the intact spine for
range of motion (ROM), sagittal alignment and instantaneous center of rotation
(ICR), each cadaver underwent 4 consecutive surgeries: 2-level artificial disc
replacement (ADR) from C4 to C6 (ADR surgery); 2-level ACDF from C4 to C6 (ACDF
surgery); hybrid C4-5 ACDF and C5-6 ADR (ACDF+ADR surgery); and hybrid C4-5 ADR
and C5-6 ACDF (ADR+ACDF surgery). The ROM and ICR of adjacent intact segments (C3
4; C6-7), and whole sagittal alignment were revaluated. RESULTS: Two-level ACDF
resulted in increased ROM at C3-4 and C6-7 compared with intact spine. ROM was
significantly different to intact spine using ACDF surgery at C3-C4 and C6-C7 and
ROM was increased with ACDF+ADR surgery at C6-C7 (all P<0.05). No improvement in
sagittal alignment was observed with any approach. The localization of the ICR
shifted upwards and anteriorly at C3-C4 after reconstruction. ICR changes at C3
C4 were greatest for ADR+ACDF surgery and were significantly different to ACDF
surgery (P<0.05), but not between ADR surgery and ACDF+ADR surgery. At C6-C7, the
ICR was more posterior and superior than in the intact condition. The greatest
change in ICR was observed in ACDF surgery at the C6-C7 level, significantly
different from the other groups (P<0.05). CONCLUSIONS: For 2-level
reconstruction, hybrid surgery and ADR did not alter ROM and minimally changed
ICR at the adjacent-level. The type of surgery had a significant impact on the
ICR location. This suggests that hybrid surgery may be a viable option for 2
level cervical surgery.
PMID- 25853774
TI - Assessment of Low-Contrast Resolution for the American College of Radiology
Computed Tomographic Accreditation Program: What Is the Impact of Iterative
Reconstruction?
AB - OBJECTIVE: To compare contrast-to-noise ratio (CNR) thresholds with visual
assessment of low-contrast resolution (LCR) in filtered back projection (FBP) and
iteratively reconstructed (IR) computed tomographic (CT) images. METHODS:
American College of Radiology (ACR) CT accreditation phantom LCR images were
acquired at CTDIvol levels of 8, 12, and 16 mGy using 2 scanner models and
reconstructed using one FBP and 2 IR kernels. Acquisitions were repeated 100
times. Three board-certified medical physicists blindly reviewed the LCR section
images. Pass-percentage rates (PPRs) using previous and current ACR CT
accreditation criteria were compared. RESULTS: Observer PPRs for FBP images were
less than 32%. For IR images, 5 of 18 settings/dose/model configurations had PPRs
greater than 32% (maximum 76.3%). For CNR evaluation of FBP images, PPRs for 15
configurations were greater than 70%. For IR images, all PPRs were at least 96%.
CONCLUSIONS: The CNR threshold used by the ACR CT accreditation program yields
higher PPRs than visual assessment of LCR, potentially resulting in lower-quality
images passing the ACR CNR criteria.
PMID- 25853775
TI - Graft Kidney Torsion After Simultaneous Kidney-Pancreas Transplant: Report of 2
Cases and Literature Review.
AB - Torsion of an allograft kidney is an extremely rare and potentially reversible
complication. Imaging diagnosis plays a crucial role because of the absence of
specific clinical features. We report 2 cases in which kidney torsion after
simultaneous kidney-pancreas transplant was diagnosed by ferumoxytol-enhanced
magnetic resonance imaging/angiography and present a review of the relevant
literature. Radiologists and clinicians should be aware of this entity because
graft salvage depends on rapid diagnosis and surgical detorsion.
PMID- 25853776
TI - Automatic Brain Portion Segmentation From Magnetic Resonance Images of Head Scans
Using Gray Scale Transformation and Morphological Operations.
AB - OBJECTIVE: To develop an automatic skull stripping method for magnetic resonance
imaging (MRI) of human head scans. METHODS: The proposed method is based on gray
scale transformation and morphological operations. RESULTS: The proposed method
has been tested with 20 volumes of normal T1-weighted images taken from Internet
Brain Segmentation Repository. Experimental results show that the proposed method
gives better results than the popular skull stripping methods Brain Extraction
Tool and Brain Surface Extractor. The average value of Jaccard and Dice
coefficients are 0.93 and 0.962 respectively. CONCLUSIONS: In this article, we
have proposed a novel skull stripping method using intensity transformation and
morphological operations. This is a low computational complexity method but gives
competitive or better results than that of the popular skull stripping methods
Brain Surface Extractor and Brain Extraction Tool.
PMID- 25853777
TI - Validity of measurement of shear modulus by ultrasound shear wave elastography in
human pennate muscle.
AB - Ultrasound shear wave elastography is becoming a valuable tool for measuring
mechanical properties of individual muscles. Since ultrasound shear wave
elastography measures shear modulus along the principal axis of the probe (i.e.,
along the transverse axis of the imaging plane), the measured shear modulus most
accurately represents the mechanical property of the muscle along the fascicle
direction when the probe's principal axis is parallel to the fascicle direction
in the plane of the ultrasound image. However, it is unclear how the measured
shear modulus is affected by the probe angle relative to the fascicle direction
in the same plane. The purpose of the present study was therefore to examine
whether the angle between the principal axis of the probe and the fascicle
direction in the same plane affects the measured shear modulus. Shear modulus in
seven specially-designed tissue-mimicking phantoms, and in eleven human in-vivo
biceps brachii and medial gastrocnemius were determined by using ultrasound shear
wave elastography. The probe was positioned parallel or 20 degrees obliquely to
the fascicle across the B-mode images. The reproducibility of shear modulus
measurements was high for both parallel and oblique conditions. Although there
was a significant effect of the probe angle relative to the fascicle on the shear
modulus in human experiment, the magnitude was negligibly small. These findings
indicate that the ultrasound shear wave elastography is a valid tool for
evaluating the mechanical property of pennate muscles along the fascicle
direction.
PMID- 25853780
TI - Microbiome: Taking advantage of quorum sensing.
PMID- 25853778
TI - Urinary tract infections: epidemiology, mechanisms of infection and treatment
options.
AB - Urinary tract infections (UTIs) are a severe public health problem and are caused
by a range of pathogens, but most commonly by Escherichia coli, Klebsiella
pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus
saprophyticus. High recurrence rates and increasing antimicrobial resistance
among uropathogens threaten to greatly increase the economic burden of these
infections. In this Review, we discuss how basic science studies are elucidating
the molecular details of the crosstalk that occurs at the host-pathogen
interface, as well as the consequences of these interactions for the
pathophysiology of UTIs. We also describe current efforts to translate this
knowledge into new clinical treatments for UTIs.
PMID- 25853781
TI - Bacterial evolution: Cutting out the carBs feeds a bistable switch.
PMID- 25853779
TI - Recent functional insights into the role of (p)ppGpp in bacterial physiology.
AB - The alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively
referred to as (p)ppGpp) are involved in regulating growth and several different
stress responses in bacteria. In recent years, substantial progress has been made
in our understanding of the molecular mechanisms of (p)ppGpp metabolism and
(p)ppGpp-mediated regulation. In this Review, we summarize these recent insights,
with a focus on the molecular mechanisms governing the activity of the RelA/SpoT
homologue (RSH) proteins, which are key players that regulate the cellular levels
of (p)ppGpp. We also discuss the structural basis of transcriptional regulation
by (p)ppGpp and the role of (p)ppGpp in GTP metabolism and in the emergence of
bacterial persisters.
PMID- 25853782
TI - [Objective Criteria in the Medicinal Therapy for Type II Diabetes: An Analysis of
the Patients' Perspective with Analytic Hierarchy Process and Best-Worst
Scaling].
AB - BACKGROUND: The patient's perspective with regard to decision criteria of
alternative treatment options has hardly been analysed. The objective of any
intervention in health-care is to increase the patient's benefit. OBJECTIVE: This
study aimed to analyse the patient-relevant decision criteria in the medicinal
therapy of type II diabetes. The characteristics of a drug therapy that are
relevant for the choice of the patients should be revealed. METHOD: An
explorative qualitative study (N=15) in combination with a quantitative survey
(in total N=388) using Analytic Hierarchy Process and Best-Worst Scaling aimed at
the determination of the importance of patient-relevant decision criteria.
RESULTS: The quantitative AHP- and BWS survey resulted in a clear dominance of
the attribute "HbA1c level" and its optimal settings, for both with oral anti
diabetics treated patients (OAD) and insulin-treated patients. In the group of
the OAD patients both methods independently showed the same ranking of the
following 3 ranks: "delay of insulin therapy" (rank 2), "occurrence of
hypoglycaemia" (rank 3) and "weight changes" (rank 4). For insulin patients "the
occurrence of hypoglycaemia" follows in the AHP on the second rank and in the BWS
on the 3(rd) rank. Compared to OAD patients, the relevance of the target
criterion "weight changes" decreases in the group of the insulin patients in the
AHP on the last rank (rank 7) and in the BWS on the second last rank (rank 6).
CONCLUSION: For the first time the methods of AHP and BWS were combined to assess
how patients weight between different characteristics of the treatment in type II
diabetes and which influence those criteria of therapy have on the patient's
benefit. Both patient groups show differences in the horizon of experience and
thus in the ranking of the decision criteria.
PMID- 25853784
TI - From the editor.
PMID- 25853783
TI - Electrochemical fabrication of graphene nanomesh via colloidal templating.
AB - A simple electrochemical fabrication of graphene nanomesh (GNM) via colloidal
templating is reported for the first time. The process involves the arraying of
polystyrene (PS) spheres onto a CVD-deposited graphene, electro-deposition of
carbazole units, removal of the PS template and electrochemical oxidative
etching. The GNM was characterized by scanning electron microscopy (SEM), atomic
force microscopy (AFM) and Raman spectroscopy.
PMID- 25853785
TI - Older women with intellectual disability and the meaning of aging.
AB - Aging with intellectual disability has become an important topic in light of the
significant increase in life expectancy of this population. More specifically,
the combination of gender, age, and intellectual disability raises unique social
issues. The aim of this research was to capture and analyze the aging experience
of women with intellectual disability from their own voice and viewpoint within
the Israeli experience. A phenomenological qualitative method was used in this
study. In-depth interviews were conducted with 19 women with mild-to-moderate
intellectual disability. Four key themes arose from the interviews: (a) the
importance of work and reluctance to retire, (b) ageism and the fear of getting
old, (c) the importance of a significant partner in old age, and (d) today's
positive self-perception. A meaningful aging process can be constructed within
the context of gender and disability. It was manifested in this study as a
disability-neutral experience. However, ageism and negative attitudes toward old
age still need to be addressed.
PMID- 25853788
TI - Prurigo Pigmentosa After Bariatric Surgery.
PMID- 25853789
TI - Ability of wild type mouse bioassay to detect bovine spongiform encephalopathy
(BSE) in the presence of excess scrapie.
AB - INTRODUCTION: Scrapie and bovine spongiform encephalopathy (BSE) are
transmissible spongiform encephalopathies (TSEs) which naturally affect small and
large ruminants respectively. However, small ruminants, which are susceptible to
BSE under experimental conditions, have been exposed to the same or similar
contaminated food additives as cattle. To date two natural cases of BSE in small
ruminants have been reported. As a result surveillance projects, combined with
appropriate control measures, have been established throughout the European Union
(EU) to minimize the overall incidence of small ruminant TSEs. Although BSE can
be differentiated from classical scrapie (subsequently referred to as scrapie) if
appropriate discriminatory tests are applied, the value of these tests in
BSE/scrapie co-infection scenarios has not been evaluated fully. Mouse bioassay
is regarded as the gold standard regarding differentiation of distinct TSE
strains and has been used as to resolve TSE cases were laboratory tests produced
equivocal results. However, the ability of this method to discriminate TSE
strains when they co-exist has not been examined systematically. To address this
issue we prepared in vitro mixtures of ovine BSE and scrapie and used them to
challenge RIII, C57BL/6 and VM mice. RESULTS: Disease phenotype analysis in all
three mouse lines indicated that most phenotypic parameters (attack rates,
incubation periods, lesion profiles and Western blots) were compatible with
scrapie phenotypes as were immunohistochemistry (IHC) data from RIII and C57BL/6
mice. However, in VM mice that were challenged with BSE/scrapie mixtures a single
BSE-associated IHC feature was identified, indicating the existence of BSE in
animals where the scrapie phenotype was dominant. CONCLUSIONS: We conclude that
wild type mouse bioassay is of limited value in detecting BSE in the presence of
scrapie particularly if the latter is in relative excess.
PMID- 25853790
TI - 1',5'-Anhydro-L-ribo-hexitol Adenine Nucleic Acids (alpha-L-HNA-A): Synthesis and
Chiral Selection Properties in the Mirror Image World.
AB - The synthesis and a preliminary investigation of the base pairing properties of
(6' -> 4')-linked 1',5'-anhydro-L-ribo-hexitol nucleic acids (alpha-L-HNA) have
herein been reported through the study of a model oligoadenylate system in the
mirror image world. Despite its considerable preorganization due to the rigidity
of the "all equatorial" pyranyl sugar backbone, alpha-L-HNA represents a
versatile informational biopolymer, in view of its capability to cross
communicate with natural and unnatural complements in both enantiomeric forms.
This seems the result of an inherent flexibility of the oligonucleotide system,
as witnessed by the singular formation of iso- and heterochiral associations
composed of regular, enantiomorphic helical structures. The peculiar properties
of alpha-L-HNA (and most generally of the alpha-HNA system) provide new elements
in our understanding of the structural prerequisites ruling the stereoselectivity
of the hybridization processes of nucleic acids.
PMID- 25853791
TI - Impact of PACAP and PAC1 receptor deficiency on the neurochemical and behavioral
effects of acute and chronic restraint stress in male C57BL/6 mice.
AB - Acute restraint stress (ARS) for 3 h causes corticosterone (CORT) elevation in
venous blood, which is accompanied by Fos up-regulation in the paraventricular
nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP
deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up
regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so
in PAC1-deficient animals. We noted that both PACAP- and PAC1-deficiency greatly
attenuate CORT elevation after ARS when CORT measurements are performed on trunk
blood following euthanasia by abrupt cervical separation: this latter observation
is of critical importance in assessing the role of PACAP neurotransmission in
ARS, based on previous reports in which serum CORT was sampled from trunk blood.
Seven days of chronic restraint stress (CRS) induces non-habituating CORT
elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6
mice. Both CORT elevation and weight loss following 7-day CRS are severely
blunted in PACAP-deficient mice, but only slightly in PAC1-deficient mice.
However, longer periods of daily restraint (14-21 days) resulted in sustained
weight loss and elevated CORT in wild-type mice, and these effects of long-term
chronic stress were attenuated or abolished in both PACAP- and PAC1-deficient
mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate
some of the PACAP-dependent central effects of ARS and short-term (<7 days) CRS
on the hypothalamo-pituitary-adrenal (HPA) axis, the PAC1 receptor plays a
prominent role in mediating PACAP-dependent HPA axis activation, and hypophagia,
during long-term (>7 days) CRS.
PMID- 25853792
TI - Inflammatory and cardiometabolic risk on obesity: role of environmental
xenoestrogens.
AB - CONTEXT: Some chemicals used in consumer products or manufacturing (eg, plastics,
pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect
immune responses and have recently emerged as a new risk factors for obesity and
cardiovascular disease. However, the extent and impact on health of chronic
exposure of the general population to XEs are still unknown. OBJECTIVE: The
objective of the study was to investigate the levels of XEs in plasma and adipose
tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing
bariatric surgery and their cardiometabolic impact in an obese state. DESIGN AND
PARTICIPANTS: We evaluated XE levels in plasma and visceral and subcutaneous AT
samples of Portuguese obese (body mass index >= 35 kg/m(2)) women undergoing
bariatric surgery. Association with metabolic parameters and 10-year
cardiovascular disease risk was assessed, according to menopausal status (73 pre-
and 48 postmenopausal). Levels of XEs were determined by gas chromatography with
electron-capture detection. Anthropometric and biochemical data were collected
prior to surgery. Adipocyte size was determined on tissue sections obtained
during surgery. RESULTS: Our data show that XEs are pervasive in this obese
population. Distribution of individual and concentration of total XEs differed
between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation
was different between pre- and postmenopausal women. Significant associations
between XE levels and metabolic and inflammatory parameters were found. In
premenopausal women, XEs in plasma seem to be a predictor of 10-year
cardiovascular disease risk. CONCLUSIONS: Our findings point toward a different
distribution of XE between plasma and AT in pre- and postmenopausal women, and
reveal the association between XEs on the development of metabolic abnormalities
in obese premenopausal women.
PMID- 25853793
TI - ARMC5 Mutations in a Large Cohort of Primary Macronodular Adrenal Hyperplasia:
Clinical and Functional Consequences.
AB - CONTEXT: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare
cause of primary adrenal Cushing's syndrome (CS). ARMC5 germline mutations have
been identified recently in PBMAH. OBJECTIVE: To determine the prevalence of
ARMC5 mutations and analyze genotype-phenotype correlation in a large cohort of
unrelated PBMAH patients with subclinical or clinical CS. PATIENTS AND METHODS:
ARMC5 was sequenced in 98 unrelated PBMAH index cases. PBMAH was identified by
bilateral adrenal nodular enlargement on computed tomography scan. The effect on
apoptosis of ARMC5 missense mutants was tested in H295R and HeLa cells. Clinical
and hormonal data were collected including midnight and urinary free cortisol
levels, ACTH, androgens, renin/aldosterone ratio, cortisol after overnight
dexamethasone suppression test, cortisol and 17-hydroxyprogesterone after ACTH 1
24 stimulation and illegitimate receptor responses. Computed tomography and
histological reports were analyzed. RESULTS: ARMC5-damaging mutations were
identified in 24 patients (26%). The missense mutants and the p.F700del deletion
were unable to induce apoptosis in both H295R and HeLa cell lines, unlike the
wild-type gene. ARMC5-mutated patients showed an overt CS more frequently,
compared to wild-type patients: lower ACTH, higher midnight plasma cortisol,
urinary free cortisol, and cortisol after dexamethasone suppression test (P =
.003, .019, .006, and <.001, respectively). Adrenals of patients with mutations
were bigger and had a higher number of nodules (P = .001 and <.001,
respectively). CONCLUSIONS: ARMC5 germline mutations are common in PBMAH. Index
cases of mutation carriers show a more severe hypercortisolism and larger
adrenals. ARMC5 genotyping may help to identify clinical forms of PBMAH better
and may also allow earlier diagnosis of this disease.
PMID- 25853794
TI - A photochromic sensor microchip for high-performance multiplex metal ions
detection.
AB - Current multi-analytes chips are limited with requiring numbers of sensors,
complex synthesis and compounds screen. It is expected to develop new principles
and techniques to achieve high-performance multi-analytes testing with facile
sensors. Here, we investigated the correlative multi-states properties of a
photochromic sensor (spirooxazine), which is capable of a selective and cross
reactive sensor array for discriminated multi-analytes (11 metal ions) detection
by just one sensing compound. The multi-testing sensor array performed in dark,
ultraviolet or visual stimulation, corresponding to different molecular states of
spirooxazine metal ions coordination. The facile photochromic microchip
contributes a multi-states array sensing method, and will open new opportunities
for the development of advanced discriminant analysis for complex analytes.
PMID- 25853795
TI - A multi-center randomized controlled trial to compare a self-ligating bracket
with a conventional bracket in a UK population: Part 1: Treatment efficiency.
AB - OBJECTIVE: To use a two-arm parallel trial to compare treatment efficiency
between a self-ligating and a conventional preadjusted edgewise appliance system.
MATERIALS AND METHODS: A prospective multi-center randomized controlled clinical
trial was conducted in three hospital orthodontic departments. Subjects were
randomly allocated to receive treatment with either a self-ligating (3M
SmartClip) or conventional (3M Victory) preadjusted edgewise appliance bracket
system using a computer-generated random sequence concealed in opaque envelopes,
with stratification for operator and center. Two operators followed a
standardized protocol regarding bracket bonding procedure and archwire sequence.
Efficiency of each ligation system was assessed by comparing the duration of
treatment (months), total number of appointments (scheduled and emergency
visits), and number of bracket bond failures. RESULTS: One hundred thirty-eight
subjects (mean age 14 years 11 months) were enrolled in the study, of which 135
subjects (97.8%) completed treatment. The mean treatment time and number of
visits were 25.12 months and 19.97 visits in the SmartClip group and 25.80 months
and 20.37 visits in the Victory group. The overall bond failure rate was 6.6% for
the SmartClip and 7.2% for Victory, with a similar debond distribution between
the two appliances. No significant differences were found between the bracket
systems in any of the outcome measures. No serious harm was observed from either
bracket system. CONCLUSIONS: There was no clinically significant difference in
treatment efficiency between treatment with a self-ligating bracket system and a
conventional ligation system.
PMID- 25853796
TI - Impact of wearing fixed orthodontic appliances on quality of life among
adolescents: Case-control study.
AB - OBJECTIVE: To investigate the impact of wearing a fixed orthodontic appliance on
oral health-related quality of life (OHRQoL) among adolescents. MATERIALS AND
METHODS: A case-control study (1 ? 2) was carried out with a population-based
randomized sample of 327 adolescents aged 11 to 14 years enrolled at public and
private schools in the City of Brumadinho, southeast of Brazil. The case group (n
= 109) was made up of adolescents with a high negative impact on OHRQoL, and
the control group (n = 218) was made up of adolescents with a low negative
impact. The outcome variable was the impact on OHRQoL measured by the Brazilian
version of the Child Perceptions Questionnaire (CPQ 11-14) - Impact Short Form
(ISF:16). The main independent variable was wearing fixed orthodontic appliances.
Malocclusion and the type of school were identified as possible confounding
variables. Bivariate and multiple conditional logistic regressions were employed
in the statistical analysis. RESULTS: A multiple conditional logistic regression
model demonstrated that adolescents wearing fixed orthodontic appliances had a
4.88-fold greater chance of presenting high negative impact on OHRQoL (95% CI:
2.93-8.13; P < .001) than those who did not wear fixed orthodontic appliances. A
bivariate conditional logistic regression demonstrated that malocclusion was
significantly associated with OHRQoL (P = .017), whereas no statistically
significant association was found between the type of school and OHRQoL (P =
.108). CONCLUSIONS: Adolescents who wore fixed orthodontic appliances had a
greater chance of reporting a negative impact on OHRQoL than those who did not
wear such appliances.
PMID- 25853797
TI - The ONIOM Method and Its Applications.
PMID- 25853798
TI - Influence of Immunogenicity of Allogeneic Bone Marrow Mesenchymal Stem Cells on
Bone Tissue Engineering.
AB - Allogeneic bone marrow mesenchymal stem cell (allo-BMSC)-based tissue-engineered
bone (TEB) has great potential for bone defect repair. However, the
immunogenicities and biological roles of allo-BMSCs are still controversial. In
this study, we established an animal model of critical-sized mandibular defect in
beagle dogs and compared the repairing effects of allo-BMSC-based TEB with
autogenic BMSC (auto-BMSC)-based TEB without the administration of
immunosuppressants. During the first 2 weeks postimplantation, a transient immune
response in the allo-BMSC group was detected with an increase in proinflammation
cytokines TNF-alpha, IFN-gamma, and IL-2, a declination of anti-inflammation
cytokine IL-10, and an increase in percentages of CD4(+) and CD8(+) T-cell
subsets in peripheral blood. Nevertheless, there was no significant difference in
bone union achievement, bone mineral density, and biomechanical properties
between the two groups at 12 and 24 weeks postimplantation. Further subcutaneous
implantation of allo-BMSCs/scaffold also exhibited the similar transient immune
responses in the first 2 weeks postimplantation but followed by a decreased bone
formation at 4 and 8 weeks postimplantation. These findings indicate that allo
BMSCs can induce a transient immunoreaction, which may temporally delay the
osteogenesis of allo-BMSC/scaffold complex in early stage of in vivo
implantation, whereas the long-term engineered bone formation was not affected.
PMID- 25853801
TI - Ruling out coronary artery disease in women with atypical chest pain: results of
calcium score combined with coronary computed tomography angiography and
associated radiation exposure.
AB - BACKGROUND: To assess the presence of coronary artery disease (CAD) in women with
atypical chest pain with low or intermediate risk for significant CAD by means of
calcium scoring (CaSc) combined with coronary computed tomography angiography
(CCTA) and to estimate the equivalent radiation dose in women. PATIENTS AND
METHODS: From December 2011 until July 2013, all consecutively performed cardiac
CTs in women with atypical chest pain were included prospectively in the present
study. Both CaSc and CCTA were obtained by a dual source flying focal spot 2*64
slice Somatom Definition Flash. Absence of CAD was defined as CaSc 0 and absence
of noncalcified plaques. Presence of CAD was determined as CaSc>0 and/or presence
of noncalcified plaques. The impact on patient management was also scored within
our patient cohort. RESULTS: A total of 1033 procedures in 1014 women (mean age
59+/-10 years; mean BMI 26+/-8) were analyzed. In 520 (51%) women, CAD was
absent. In 494 (49%) women, CAD was diagnosed, and in this subgroup the mean CaSc
was 137+/-229. Thirty-seven (7%) of 494 women with CAD showed only noncalcified
plaques. The mean equivalent radiation dose for the cardiac CTs of 1014 women was
2.2+/-1.6 mSv. CONCLUSION: Combined CaSc and CCTA excludes CAD in approximately
50% of women with atypical chest pain, and delivers a modest radiation dose of
2.2+/-1.6 mSv. CCTA has a substantial impact on patient management and can thus
be advocated as first diagnostic tool in excluding CAD in women with atypical
chest pain in terms of latest generation equipment with emphasize on radiation
reduction techniques.
PMID- 25853800
TI - 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation
in cancer.
AB - BACKGROUND: The discovery of cytosine hydroxymethylation (5hmC) as a mechanism
that potentially controls DNA methylation changes typical of neoplasia prompted
us to investigate its behaviour in colon cancer. 5hmC is globally reduced in
proliferating cells such as colon tumours and the gut crypt progenitors, from
which tumours can arise. RESULTS: Here, we show that colorectal tumours and
cancer cells express Ten-Eleven-Translocation (TET) transcripts at levels similar
to normal tissues. Genome-wide analyses show that promoters marked by 5hmC in
normal tissue, and those identified as TET2 targets in colorectal cancer cells,
are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer
cells confirm that these promoters are resistant to methylation gain
independently of sustained TET2 expression. We also find that a considerable
number of the methylation gain-resistant promoters marked by 5hmC in normal colon
overlap with those that are marked with poised bivalent histone modifications in
embryonic stem cells. CONCLUSIONS: Together our results indicate that promoters
that acquire 5hmC upon normal colon differentiation are innately resistant to
neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC
in tumours. Our study highlights the potential of cytosine modifications as
biomarkers of cancerous cell proliferation.
PMID- 25853802
TI - Proliferation of axial parenchymatic xylem cells is a key step in wound closure
of girdled stems in Pinus canariensis.
AB - BACKGROUND: Wounds caused by fire, herbivorism, rock impacts, etc. cause the
direct loss of photosynthetic, storage and/or vascular tissue. In addition, they
may entail other damages, such as desiccation of the exposed internal parts, or
become a gateway to infection by fungi and other pathogens. To successfully
overcome such injuries, plants must reorganize their meristems or even
differentiate new ones, producing new traumatic tissues to cover the wound and
restore the vascular connection. RESULTS: In this work we analyse the anatomical
growth response in conifers after debarking and injuring the vascular cambium,
using Pinus canariensis as model species, due to its high wound recovery ability.
Conversely to angiosperm woody species, this process is initiated and largely
driven by the damaged vascular cambium and not by proliferation in the wound
surface. We have detected alterations and switches in the divisions of cambial
cells, associated to their position relative to the surface and edges of the
wound, resulting in disordered traumatic xylem. We also describe the formation of
column-like structures, after girdling, which are in part formed by the
proliferation of xylem parenchymatous cells, associated to axial resin ducts.
CONCLUSIONS: Abundant resinosis on the wound surface, typical of conifers, is an
efficient barrier against opportunistic fungi, insects, etc. but it also hinders
the healing process directly from the surface. Thus, wound closure must be
largely carried out from the wound margins, being a much slower process, which
very often remains unconcluded for long years. This work also describes for the
first time the proliferation of inner parenchymatous cells to form column-like
structures, which accelerates wound closure in girdled P. canariensis.
Irregularities in the surface of the healing edge or column-like structures
result in the production of disordered vascular tissues, compromising their
future functionality, and which must be overcome through the fast restoration of
the proper polarity in vascular cambium.
PMID- 25853803
TI - Marked seasonality and high spatial variability of protist communities in shallow
freshwater systems.
AB - Small eukaryotes have key roles in aquatic ecosystems, influencing their local
environment, global biogeochemical cycles and climate. Their impact depends on
community structure, which varies along time. However, very few studies take into
account temporal variation. This is especially true for small, shallow freshwater
systems, which remain largely understudied despite their wide variety, global
surface and intense microbial activity. We have monthly followed changes in the
community structure of small microbial eukaryotes (0.2-5 MUm cell diameter) for 2
years in four ponds and one brook located in North-Western France based on
massive 18S rDNA amplicon 454 pyrosequencing. We detected a total of 3742
stringently defined operational taxonomic units (OTUs) encompassing all
recognized eukaryotic supergroups and lineages of uncertain affiliation. Although
geographically close, protist communities in the five ecosystems were
contrasting, with very few shared OTUs, suggesting that environmental selection
mainly drives community structure. The temporal dynamics of different high-rank
taxa appeared complex and rapid at monthly scales. Despite this, a clear and
reproducible seasonality was observed. As expected, low-abundance OTUs dominated
the community. Although some of them appeared sporadically or remained at low
frequencies during the survey, others occasionally reached relatively high
abundances, sometimes recurrently. This shows that at least a fraction of low
abundance eukaryotes constitutes a seed bank. The annual proportion of primary
producers, free-living heterotrophs and parasites appeared remarkably constant
among the different ecosystems, suggesting underlying trends of ecosystem
carrying capacity for these functional groups.
PMID- 25853804
TI - alpha2u-globulins mediate manipulation of host attractiveness in Toxoplasma
gondii-Rattus novergicus association.
AB - Uninfected female rats (Rattus novergicus) exhibit greater attraction to the
males infected with protozoan parasite Toxoplasma gondii. This phenomenon is
contrary to the aversion towards infected males observed in multitude of other
host-parasite associations. In this report, we describe a proximate mechanism for
this anomaly. We demonstrate that T. gondii infection enhances hepatic production
and urinary excretion of alpha2u-globulins in rats. We further demonstrate that
alpha2u-globulins are sufficient to recapitulate male sexual attractiveness akin
to effects of the infection. This manipulation possibly results in greater
horizontal transmission of this parasite between the infected male and the
uninfected female. It supports the notion that in some evolutionary niches
parasites can alter host sexual signaling, likely leading to an increased rate of
sexual transmission.
PMID- 25853805
TI - The Trigger Tool as a Method to Measure Harmful Medication Errors in Children.
AB - OBJECTIVES: The aim of this study was to improve medication safety for children;
it is important to quantify the occurrence of preventable medication errors
(MEs). A trigger tool may be an effective and time-saving strategy, but its
measurement performance is unclear. Therefore, we aimed to estimate the
performance of a pediatric medication-focused trigger tool in detecting harmful
MEs. METHODS: First, we established a multifaceted method as a reference
comparison. Second, we compared the pediatric medication-focused trigger tool
with the multifaceted method in a new cohort of patients. All patients admitted
in February and March 2013 were screened using the trigger tool and the
multifaceted method to obtain full verification. Data collection was performed in
separate teams to guarantee blinding of the test results. RESULTS: Review of the
clinical records and the voluntary incident reports was most effective in
detecting harmful MEs, so this approach was chosen as a reference comparison. In
the second part of the study, 369 patients were included. The multifaceted method
identified 33 harmful MEs. In contrast, the trigger tool did not identify any
harm. When the 2 symptoms pain and nausea/vomiting were added to the trigger
tool, 19 harmful MEs were identified. This extended trigger tool resulted in a
sensitivity of 21.2 and a positive predictive value of 36.8. CONCLUSIONS: The
original pediatric medication-focused trigger tool yielded only false-positive
scores and left unsafe situations undiscovered. We conclude that a multifaceted
method remains the preferred method to detect harmful MEs. The additional value
of the trigger tool stays unclear.
PMID- 25853806
TI - Evaluation of the Prevalence of Shielding in Patients Undergoing Conventional
Radiological Procedures (1 Work Shift-1 X-ray Room).
AB - OBJECTIVES: This study aimed to evaluate the prevalence of shielding in patients
undergoing conventional radiological procedures (1 work shift-1 x-ray room).The
increased number of patients undergoing x-ray examinations has created a global
concern due to the stochastic and nonstochastic association with x-ray exposure.
Shielding is an efficient method of protecting radiosensitive organs when
performing radiological examinations. MATERIALS AND METHODS: Thirty radiography
students were sent to conventional radiology departments to act as observers in
the control booth of an x-ray room when a radiological procedure was being
performed. RESULTS: Of the 30 hospitals evaluated, 13% regarded shielding of
radiosensitive organs. The prevalence of shielding in the hospitals where
shielding of radiosensitive organs was implemented varied from 5.2% to 14%.
CONCLUSION: The results of this study showed that shielding of radiosensitive
organs was not performed in the majority of hospitals. More studies are needed to
establish the potential causes of low shielding prevalence.If these findings,
which were obtained over 1 work shift and in 1 x-ray room, are representative of
a large number of medical imaging centers, this raises global concerns regarding
shielding of radiosensitive organs, in particular gonad shielding.
PMID- 25853807
TI - Complications of Non-Operating Room Procedures: Outcomes From the National
Anesthesia Clinical Outcomes Registry.
AB - OBJECTIVES: This study examines the impact of procedural locations and types of
anesthetics on patient outcomes in non-operating room anesthesia (NORA)
locations. The National Anesthesia Clinical Outcomes Registry database was
examined to compare OR to NORA anesthetic complications and patient demographics.
METHODS: The National Anesthesia Clinical Outcomes Registry database was examined
for all patient procedures from 2010 to 2013. A total of 12,252,846 cases were
analyzed, with 205 practices contributing information, representing 1494
facilities and 7767 physician providers. Cases were separated on the basis of
procedure location, OR, or NORA. Subgroup analysis examined outcomes from
specific subspecialties. RESULTS: Non-OR anesthesia procedures were performed on
a higher percentage of patients older than 50 years (61.92% versus 55.56%, P <
0.0001). Monitored anesthesia care (MAC) (20.15%) and sedation (2.05%) were more
common in NORA locations. The most common minor complications were postoperative
nausea and vomiting (1.06%), inadequate pain control (1.01%), and hemodynamic
instability (0.62%). The most common major complications were serious hemodynamic
instability (0.10%) and upgrade of care (0.10%). There was a greater incidence of
complications in cardiology and radiology locations. Overall mortality was higher
in OR versus NORA (0.04% versus 0.02%, P < 0.0001). Subcategory analysis showed
increased incidence of death in cardiology and radiology locations (0.05%).
CONCLUSIONS: Non-OR anesthesia procedures have lower morbidity and mortality
rates than OR procedures, contrary to some previously published studies. However,
the increased complication rates in both the cardiology and radiology locations
may need to be the target of future safety investigations. Providers must ensure
proper monitoring of patients, and NORA locations need to be held to the same
standard of care as the main operating room. Further studies need to identify at
risk patients and procedures that may predispose patients to complications.
PMID- 25853808
TI - Accountability: Challenges to Getting It Right.
AB - Patient safety experts debated accountability in health care at the 2014 annual
National Patient Safety Foundation Congress. The debate reflected the struggles
organizations are facing with ensuring a responsible workforce committed to
patient safety versus the need to redesign flawed systems that are error prone.
The question, "is it the systems or the individual?" was at issue. This article
proposes that it is the wrong question, and the failure to apply patient safety
science in clinical practice is contributing to the ambiguity fueling the debate.
To transform accountability from a source of confusion to a powerful tool for
fulfilling health care's fiduciary responsibility to protect patients from harm,
we need to reframe our approach. This article presents the science and strategies
to create clarity that will redirect the dialogue from a debate in which
accountability resides to one about learning for improvement when adverse events
occur.
PMID- 25853809
TI - European flint landraces grown in situ reveal adaptive introgression from modern
maize.
AB - We have investigated the role of selection in the determination of the detected
levels of introgression from modern maize hybrid varieties into maize landraces
still cultivated in situ in Italy. We exploited the availability of a historical
collection of landraces undertaken before the introduction and widespread use of
modern maize, to analyse genomic changes that have occurred in these maize
landraces over 50 years of co-existence with hybrid varieties. We have combined a
previously published SSR dataset (n=21) with an AFLP loci dataset (n=168) to
provide higher resolution power and to obtain a more detailed picture. We show
that selection pressures for adaptation have favoured new alleles introduced by
migration from hybrids. This shows the potential for analysis of historical
introgression even over this short period of 50 years, for an understanding of
the evolution of the genome and for the identification of its functionally
important regions. Moreover, this demonstrates that landraces grown in situ
represent almost unique populations for use for such studies when the focus is on
the domesticated plant. This is due to their adaptation, which has arisen from
their dynamic evolution under a continuously changing agro-ecological
environment, and their capture of new alleles from hybridisation. We have also
identified loci for which selection has inhibited introgression from modern
germplasm and has enhanced the distinction between landraces and modern maize.
These loci indicate that selection acted in the past, during the formation of the
flint and dent gene pools. In particular, the locus showing the strongest signals
of selection is a Misfit transposable element. Finally, molecular
characterisation of the same samples with two different molecular markers has
allowed us to compare their performances. Although the genetic-diversity and
population-structure analyses provide the same global qualitative pattern, which
thus provides the same inferences, there are differences related to their natures
and characteristics.
PMID- 25853811
TI - Correction: breast cancer screening in Saudi Arabia: free but almost no takers.
AB - [This corrects the article DOI: 10.1371/journal.pone.0119051.].
PMID- 25853810
TI - Nitric oxide sustains IL-1beta expression in human dendritic cells enhancing
their capacity to induce IL-17-producing T-cells.
AB - The role played by lung dendritic cells (DCs) which are influenced by external
antigens and by their redox state in controlling inflammation is unclear. We
studied the role played by nitric oxide (NO) in DC maturation and function. Human
DCs were stimulated with a long-acting NO donor, DPTA NONOate, prior to exposure
to lipopolysaccharide (LPS). Dose-and time-dependent experiments were performed
with DCs with the aim of measuring the release and gene expression of
inflammatory cytokines capable of modifying T-cell differentiation, towardsTh1,
Th2 and Th17 cells. NO changed the pattern of cytokine release by LPS-matured
DCs, dependent on the concentration of NO, as well as on the timing of its
addition to the cells during maturation. Addition of NO before LPS-induced
maturation strongly inhibited the release of IL-12, while increasing the
expression and release of IL-23, IL-1beta and IL-6, which are all involved in
Th17 polarization. Indeed, DCs treated with NO efficiently induced the release of
IL-17 by T-cells through IL-1beta. Our work highlights the important role that NO
may play in sustaining inflammation during an infection through the preferential
differentiation of the Th17 lineage.
PMID- 25853812
TI - Mucosal-associated invariant T cell is a potential marker to distinguish
fibromyalgia syndrome from arthritis.
AB - BACKGROUND: Fibromyalgia (FM) is defined as a widely distributed pain. While many
rheumatologists and pain physicians have considered it to be a pain disorder,
psychiatry, psychology, and general medicine have deemed it to be a syndrome
(FMS) or psychosomatic disorder. The lack of concrete structural and/or
pathological evidence has made patients suffer prejudice that FMS is a medically
unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits
comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of
which show similar indications. In this study, disease specific biomarkers were
sought in blood samples from patients to facilitate objective diagnoses of FMS,
and distinguish it from RA and SpA. METHODS: Peripheral blood mononuclear cells
(PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow
cytometric analysis. The percentage of mucosal-associated invariant T (MAIT)
cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen
expression in MAIT cells were analyzed. RESULTS: There was a decrease in the MAIT
cell population in FMS, RA, and SpA compared with HD. Among the cell surface
antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a
natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule
(SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8beta
emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a
memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared
possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved
for SpA to differentiate from FMS. Furthermore, the drug treatment interruption
resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28,
inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor alpha), CD94,
NKp80, an activation marker, CD69, an integrin family member, CD49d, and a
dipeptidase, CD26, in FMS. CONCLUSIONS: Combined with the currently available
diagnostic procedures and criteria, analysis of MAIT cells offers a more
objective standard for the diagnosis of FMS, RA, and SpA, which exhibit
multifaceted and confusingly similar clinical manifestations.
PMID- 25853814
TI - Transgene expression and Bt protein content in transgenic Bt maize (MON810) under
optimal and stressful environmental conditions.
AB - Bt protein content in transgenic insect resistant (Bt) maize may vary between
tissues within plants and between plants growing under different environmental
conditions. However, it is unknown whether and how Bt protein content correlates
with transgene expression, and whether this relationship is influenced by
stressful environmental conditions. Two Bt maize varieties containing the same
transgene cassette (MON 810) were grown under optimal and stressful conditions.
Before and during stress exposure, the upper leaves were analysed for transgene
expression using quantitative RT-PCR and for Bt content using ELISA. Under
optimal conditions there was no significant difference in the transgene
expression between the two investigated Bt maize varieties whereas Bt protein
content differed significantly. Transgene expression was correlated with Bt
protein content in only one of the varieties. Under stressful environmental
conditions we found similar transgene expressions as under optimal conditions but
Bt content responded differently. These results suggest that Bt content is not
only controlled by the transgene expression but is also dependent on the genetic
background of the maize variety. Under stressful conditions the concentration of
Bt protein is even more difficult to predict.
PMID- 25853813
TI - Low birth weight at term and its determinants in a tertiary hospital of Nepal: a
case-control study.
AB - Birth weight of a child is an important indicator of its vulnerability for
childhood illness and chances of survival. A large number of infant deaths can be
averted by appropriate management of low birth weight babies and prevention of
factors associated with low birth weight. The prevalence of low birth weight
babies in Nepal is estimated to be about 12-32%.Our study aimed at identifying
major determinants of low birth weight among term babies in Nepal. A hospital
based retrospective case control study was conducted in maternity ward of
Tribhuvan University Teaching Hospital from February to July 2011. A total of 155
LBW babies and 310 controls were included in the study. Mothers admitted to
maternity ward during the study period were interviewed, medical records were
assessed and anthropometric measurements were done. Risk factors, broadly
classified into proximal and distal factors, were assessed for any association
with birth of low-birth weight babies. Regression analysis revealed that a
history of premature delivery (adjusted odds ratio; aOR5.24, CI 1.05-26.28), hard
physical work during pregnancy (aOR1.48, CI 0.97-2.26), younger age of mother
(aOR1.98, CI 1.15-3.41), mothers with haemoglobin level less than 11gm/dl
(aOR0.51, CI0.24-1.07) and lack of consumption of nutritious food during
pregnancy (aOR1.99, CI 1.28-3.10) were significantly associated with the birth of
LBW babies. These factors should be addressed with appropriate measures so as to
decrease the prevalence of low birth weight among term babies in Nepal.
PMID- 25853815
TI - Lonafarnib is a potential inhibitor for neovascularization.
AB - Atherosclerosis is a common cardiovascular disease that involves the build-up of
plaque on the inner walls of the arteries. Intraplaque neovacularization has been
shown to be essential in the pathogenesis of atherosclerosis. Previous studies
showed that small-molecule compounds targeting farnesyl transferase have the
ability to prevent atherosclerosis in apolipoprotein E-deficient mice, but the
underlying mechanism remains to be elucidated. In this study, we found that
lonafarnib, a specific inhibitor of farnesyl transferase, elicits inhibitory
effect on vascular endothelial capillary assembly in vitro in a dose-dependent
manner. In addition, we showed that lonafarnib treatment led to a dose-dependent
decrease in scratch wound closure in vitro, whereas it had little effect on
endothelial cell proliferation. These data indicate that lonafarnib inhibits
neovascularization via directly targeting endothelial cells and disturbing their
motility. Moreover, we demonstrated that pharmacological inhibition of farnesyl
transferase by lonafarnib significantly impaired centrosome reorientation toward
the leading edge of endothelial cells. Mechanistically, we found that the
catalytic beta subunit of farnesyl transferase associated with a cytoskeletal
protein important for the establishment and maintenance of cell polarity.
Additionally, we showed that lonafarnib remarkably inhibited the expression of
the cytoskeletal protein and interrupted its interaction with farnesyl
transferase. Our findings thus offer novel mechanistic insight into the
protective effect of farnesyl transferase inhibitors on atherosclerosis and
provide encouraging evidence for the potential use of this group of agents in
inhibiting plaque neovascularization.
PMID- 25853816
TI - Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in
macrophages.
AB - Botulinum neurotoxin type A (BoNT/A) is the most potent protein toxin and causes
fatal flaccid muscle paralysis by blocking neurotransmission. Application of
BoNT/A has been extended to the fields of therapeutics and biodefense.
Nevertheless, the global response of host immune cells to authentic BoNT/A has
not been reported. Employing microarray analysis, we performed global
transcriptional profiling of RAW264.7 cells, a murine alveolar macrophage cell
line. We identified 70 genes that were modulated following 1 nM BoNT/A treatment.
The altered genes were mainly involved in signal transduction, immunity and
defense, protein metabolism and modification, neuronal activities, intracellular
protein trafficking, and muscle contraction. Microarray data were validated with
real-time RT-PCR for seven selected genes including tlr2, tnf, inos, ccl4, slpi,
stx11, and irg1. Proinflammatory mediators such as nitric oxide (NO) and tumor
necrosis factor alpha (TNFalpha) were induced in a dose-dependent manner in
BoNT/A-stimulated RAW264.7 cells. Increased expression of these factors was
inhibited by monoclonal anti-Toll-like receptor 2 (TLR2) and inhibitors specific
to intracellular proteins such as c-Jun N-terminal kinase (JNK), extracellular
signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK).
BoNT/A also suppressed lipopolysaccharide-induced NO and TNFalpha production from
RAW264.7 macrophages at the transcription level by blocking activation of JNK,
ERK, and p38 MAPK. As confirmed by TLR2-/- knock out experiments, these results
suggest that BoNT/A induces global gene expression changes in host immune cells
and that host responses to BoNT/A proceed through a TLR2-dependent pathway, which
is modulated by JNK, ERK, and p38 MAPK.
PMID- 25853818
TI - Reproducibility in echocardiographic assessment of diastolic function in a
population based study (the STANISLAS Cohort study).
AB - INTRODUCTION: There is limited evidence regarding intra-observer and inter
observer variations in echocardiographic measurements of diastolic function. This
study aimed to assess this reproducibly within a population-based cohort study.
METHODS: Sixty subjects in sinus rhythm were randomly selected among 4th visit
participants of the STANISLAS Cohort (Lorraine region, France). This 4th
examination systematically included M-mode, 2-dimensional, DTI and pulsed-wave
Doppler echocardiograms. Reproducibility of variables was studied by intra-class
correlation coefficients (ICC) and Bland Altman plots. RESULTS: Our population
was on average middle-aged (50 +/- 14 y), overweight (BMI = 26 +/- 6 kg/m2) and
non-smoking (87%) with a quarter of the participants having self-declared
hypertension or treated with anti-hypertensive medication(s). Intra-observer ICC
were > 0.90 for all analyzed parameters except for left ventricular ejection
fraction (LVEF) which was 0.89 (0.81-0.93). The mean relative intra-observer
differences were small and limits of agreement of relative differences were
narrow for all considered parameters (<5% and <15% respectively). Inter-observer
ICC were > 0.90 for all analyzed parameters except for LVEF (ICC = 0.87) and both
mitral and pulmonary A wave duration (0.83 and 0.73 respectively). The mean
relative inter-observer differences were <5% for all parameters except for
pulmonary A wave duration (mean difference = 6.5%). Limits of agreement of
relative differences were narrow (<15%), except for mitral A wave duration and
velocity (both <20%) as well as left ventricular mass and pulmonary A wave
duration (both <30%). Intra-observer agreements with regard to the presence and
severity of diastolic dysfunction were excellent (Kappa = 0.93 (0.83-1.00) and
0.88 (0.75-0.99), respectively). CONCLUSION: In this validation study within the
STANISLAS cohort, diastolic function echocardiographic parameters were found to
be highly reproducible. Diastolic dysfunction consequently appears as a highly
effective clinical and research tool.
PMID- 25853817
TI - Distinctive patterns of evolution of the delta-globin gene (HBD) in primates.
AB - In most vertebrates, hemoglobin (Hb) is a heterotetramer composed of two
dissimilar globin chains, which change during development according to the
patterns of expression of alpha- and beta-globin family members. In placental
mammals, the beta-globin cluster includes three early-expressed genes,
epsilon(HBE)-gamma(HBG)-psibeta(HBBP1), and the late expressed genes, delta (HBD)
and beta (HBB). While HBB encodes the major adult beta-globin chain, HBD is
weakly expressed or totally silent. Paradoxically, in human populations HBD shows
high levels of conservation typical of genes under strong evolutionary
constraints, possibly due to a regulatory role in the fetal-to-adult switch
unique of Anthropoid primates. In this study, we have performed a comprehensive
phylogenetic and comparative analysis of the two adult beta-like globin genes in
a set of diverse mammalian taxa, focusing on the evolution and functional
divergence of HBD in primates. Our analysis revealed that anthropoids are an
exception to a general pattern of concerted evolution in placental mammals,
showing a high level of sequence conservation at HBD, less frequent and shorter
gene conversion events. Moreover, this lineage is unique in the retention of a
functional GATA-1 motif, known to be involved in the control of the developmental
expression of the beta-like globin genes. We further show that not only the mode
but also the rate of evolution of the delta-globin gene in higher primates are
strictly associated with the fetal/adult beta-cluster developmental switch. To
gain further insight into the possible functional constraints that have been
shaping the evolutionary history of HBD in primates, we calculated dN/dS (omega)
ratios under alternative models of gene evolution. Although our results indicate
that HBD might have experienced different selective pressures throughout primate
evolution, as shown by different omega values between apes and Old World Monkeys
+ New World Monkeys (0.06 versus 0.43, respectively), these estimates
corroborated a constrained evolution for HBD in Anthropoid lineages, which is
unlikely to be related to protein function. Collectively, these findings suggest
that sequence change at the delta-globin gene has been under strong selective
constraints over 65 Myr of primate evolution, likely due to a regulatory role in
ontogenic switches of gene expression.
PMID- 25853819
TI - The GAB2 and BDNF polymorphisms and the risk for late-onset Alzheimer's disease
in an elderly Brazilian sample.
AB - BACKGROUND: Evidences suggest that GAB2 and BDNF genes may be associated with
Alzheimer's disease (AD). We aimed to investigate the GAB2 rs2373115 and BDNF
rs6265 polymorphisms and the risk of AD in a Brazilian sample. METHODS: 269 AD
patients and 114 controls were genotyped with Real-time PCR. Multifactor
dimensionality reduction (MDR) was employed to explore the effects of gene-gene
interactions. RESULTS: GAB2 and BDNF were not associated with AD in our sample.
Nevertheless BDNF Val allele (rs6265) presented a synergic association with the
APOE epsilon4 allele. A multiple logistic regression demonstrated that the APOE
epsilon4 allele and years of education were the best predictors for AD. In
epsilon4 non-carriers sex, education and hypertension were independently
correlated with AD, while in epsilon4 carriers we did not observe any
association. The findings were further confirmed by bootstrapping method.
CONCLUSIONS: Our data suggest that the interaction of BDNF and APOE has
significant effect on AD. Moreover in absence of epsilon4, female sex, low level
of education and hypertension are independently associated with AD. Interventions
aimed to prevent AD should focus on these factors and also taking into account
the APOE alleles.
PMID- 25853821
TI - Simultaneous quantification of multiple urinary naphthalene metabolites by liquid
chromatography tandem mass spectrometry.
AB - Naphthalene is an environmental toxicant to which humans are exposed. Naphthalene
causes dose-dependent cytotoxicity to murine airway epithelial cells but a link
between exposure and human pulmonary disease has not been established.
Naphthalene toxicity in rodents depends on P450 metabolism. Subsequent
biotransformation results in urinary elimination of several conjugated
metabolites. Glucuronide and sulfate conjugates of naphthols have been used as
markers of naphthalene exposure but, as the current studies demonstrate, these
assays provide a limited view of the range of metabolites generated from the
parent hydrocarbon. Here, we present a liquid chromatography tandem mass
spectrometry method for measurement of the glucuronide and sulfate conjugates of
1-naphthol as well as the mercapturic acids and N-acetyl glutathione conjugates
from naphthalene epoxide. Standard curves were linear over 2 log orders. On
column detection limits varied from 0.91 to 3.4 ng; limits of quantitation from
1.8 to 6.4 ng. The accuracy of measurement of spiked urine standards was -13.1 to
+ 5.2% of target and intra-day and inter-day variability averaged 7.2 (+/- 4.5)
and 6.8 (+/- 5.0) %, respectively. Application of the method to urine collected
from mice exposed to naphthalene at 15 ppm (4 hrs) showed that glutathione
derived metabolites accounted for 60-70% of the total measured metabolites and
sulfate and glucuronide conjugates were eliminated in equal amounts. The method
is robust and directly measures several major naphthalene metabolites including
those derived from glutathione conjugation of naphthalene epoxide. The assays do
not require enzymatic deconjugation, extraction or derivatization thus
simplifying sample work up.
PMID- 25853820
TI - When is exposure to a natural disaster traumatic? Comparison of a trauma
questionnaire and disaster exposure inventory.
AB - Few studies have compared the sensitivity of trauma questionnaires to disaster
inventories for assessing the prevalence of exposure to natural disaster or
associated risk for post-disaster psychopathology. The objective of this analysis
was to compare reporting of disaster exposure on a trauma questionnaire (Brief
Trauma Questionnaire [BTQ]) to an inventory of disaster experience. Between 2011
and 2014, a sample of 841 reproductive-aged southern Louisiana women were
interviewed using the BTQ and completed a detailed inventory about exposure to
hurricanes and flooding. Post-traumatic stress disorder (PTSD) symptomology was
measured with the Post-Traumatic Stress Checklist, and depression with the
Edinburgh Depression Scale. The single question addressing disaster exposure on
the BTQ had a sensitivity of between 65% and 70% relative to the more detailed
questions. Reporting disaster exposure on the BTQ was more likely for those who
reported illness/injury due to a hurricane or flood (74%-77%) or danger (77-79%),
compared to those who reported damage (69-71%) or evacuation (64-68%). Reporting
disaster exposure on the BTQ was associated with depression (odds ratio [OR]
2.29, 95% confidence interval [CI] 1.43-3.68). A single question is unlikely to
be useful for assessing the degree of exposure to disaster across a broad
population, and varies in utility depending on the mental health outcome of
interest: the single trauma question is useful for assessing depression risk.
PMID- 25853822
TI - Unscheduled-return-visits after an emergency department (ED) attendance and
clinical link between both visits in patients aged 75 years and over: a
prospective observational study.
AB - BACKGROUND: Predictors of unscheduled return visits (URV), best time-frame to
evaluate URV rate and clinical relationship between both visits have not yet been
determined for the elderly following an ED visit. METHODS: We conducted a
prospective-observational study including 11,521 patients aged >=75-years and
discharged from ED (5,368 patients (53.5%)) or hospitalized after ED visit (6,153
patients). Logistic Regression and time-to-failure analyses including Cox
proportional model were performed. RESULTS: Mean time to URV was 17 days; 72
hour, 30-day and 90-day URV rates were 1.8%, 6.1% and 10% respectively.
Multivariate analysis indicates that care-pathway and final disposition decisions
were significantly associated with a 30-day URV. Thus, we evaluated predictors of
30-day URV rates among non-admitted and hospitalized patient groups. By using the
Cox model we found that, for non-admitted patients, triage acuity and diagnostic
category and, for hospitalized patients, that visit time (day, night) and
diagnostic categories were significant predictors (p<0.001). For URV, we found
that 25% were due to closely related-clinical conditions. Time lapses between
both visits constituted the strongest predictor of closely related-clinical
conditions. CONCLUSION: Our study shows that a decision of non-admission in
emergency departments is linked with an accrued risk of URV, and that some
diagnostic categories are also related for non-admitted and hospitalized subjects
alike. Our study also demonstrates that the best time frame to evaluate the URV
rate after an ED visit is 30 days, because this is the time period during which
most URVs and cases with close clinical relationships between two visits are
concentrated. Our results suggest that URV can be used as an indicator or
quality.
PMID- 25853824
TI - Correction: Bacterial immune evasion through manipulation of host inhibitory
immune signaling.
AB - [This corrects the article DOI: 10.1371/journal.ppat.1004644.].
PMID- 25853823
TI - Evidence for distinct coastal and offshore communities of bottlenose dolphins in
the north east Atlantic.
AB - Bottlenose dolphin stock structure in the northeast Atlantic remains poorly
understood. However, fine scale photo-id data have shown that populations can
comprise multiple overlapping social communities. These social communities form
structural elements of bottlenose dolphin (Tursiops truncatus) [corrected]
populations, reflecting specific ecological and behavioural adaptations to local
habitats. We investigated the social structure of bottlenose dolphins in the
waters of northwest Ireland and present evidence for distinct inshore and
offshore social communities. Individuals of the inshore community had a coastal
distribution restricted to waters within 3 km from shore. These animals exhibited
a cohesive, fission-fusion social organisation, with repeated resightings within
the research area, within a larger coastal home range. The offshore community
comprised one or more distinct groups, found significantly further offshore (>4
km) than the inshore animals. In addition, dorsal fin scarring patterns differed
significantly between inshore and offshore communities with individuals of the
offshore community having more distinctly marked dorsal fins. Specifically,
almost half of the individuals in the offshore community (48%) had characteristic
stereotyped damage to the tip of the dorsal fin, rarely recorded in the inshore
community (7%). We propose that this characteristic is likely due to interactions
with pelagic fisheries. Social segregation and scarring differences found here
indicate that the distinct communities are likely to be spatially and
behaviourally segregated. Together with recent genetic evidence of distinct
offshore and coastal population structures, this provides evidence for bottlenose
dolphin inshore/offshore community differentiation in the northeast Atlantic. We
recommend that social communities should be considered as fundamental units for
the management and conservation of bottlenose dolphins and their habitat
specialisations.
PMID- 25853826
TI - [The medication cycle: its impact on access to and adequate use of drugs].
PMID- 25853825
TI - Dolphins adjust species-specific frequency parameters to compensate for
increasing background noise.
AB - An increase in ocean noise levels could interfere with acoustic communication of
marine mammals. In this study we explored the effects of anthropogenic and
natural noise on the acoustic properties of a dolphin communication signal, the
whistle. A towed array with four elements was used to record environmental
background noise and whistles of short-beaked common-, Atlantic spotted- and
striped-dolphins in the Canaries archipelago. Four frequency parameters were
measured from each whistle, while Sound Pressure Levels (SPL) of the background
noise were measured at the central frequencies of seven one-third octave bands,
from 5 to 20 kHz. Results show that dolphins increase the whistles' frequency
parameters with lower variability in the presence of anthropogenic noise, and
increase the end frequency of their whistles when confronted with increasing
natural noise. This study provides the first evidence that the synergy among SPLs
has a role in shaping the whistles' structure of these three species, with
respect to both natural and anthropogenic noise.
PMID- 25853827
TI - [Essential medicines and the TRIPS Agreement: collision between the right to
health and intellectual property rights].
AB - The strengthening of pharmaceutical patent protection globally puts strains on
access to essential medicines. According to the present paper, this process has
led to the collision of the intellectual property rights adopted in the World
Trade Organization (WTO) Trade-Related Aspects of Intellectual Property Rights
(TRIPS) Agreement and the right to health stated in the International Covenant on
Economic, Social and Cultural Rights (ICESCR). Several controversies disputed in
the WTO illustrate the confrontation between countries with a powerful
pharmaceutical industry and the interests of developing countries. It is
concluded that the TRIPS-plus rules subscribed to by developing countries in free
trade agreements which give the pharmaceutical patent holder more rights than
those stipulated in the original TRIPS Agreement are incompatible with the
obligations to provide access to essential medicines under the right to health of
the ICESCR.
PMID- 25853828
TI - [Alternatives to the drug research and development model].
AB - One-third of the global population lacks access to medications; the situation is
worse in poor countries, where up to 50% of the population lacks access. The
failure of current incentive systems based in intellectual property to offer the
necessary pharmaceutical products, especially in the global south, is a call to
action. Problems related to drug access cannot be solved solely through
improvements or modifications in the existing incentive models. The intellectual
property system model does not offer sufficient innovation for developing
countries; new mechanisms that effectively promote innovation and drug access
simultaneously are needed. A binding international agreement on research and
development, negotiated under the auspices of the World Health Organization,
could provide an adequate framework for guaranteeing priority-setting,
coordination, and sustainable financing of drugs at reasonable prices for
developing countries.
PMID- 25853829
TI - [Drug prices: how they are established and existing price control systems].
AB - Price is one of the main barriers of access to medicines. It is therefore
important to understand how prices are formed and what factors determine the
amount, as well as what interventions and regulations are the most appropriate
considering their effects on access, innovation, local production and other
potential objectives of drug policy. Economic analysis has developed a set of
market models that can explain the behavior of prices, although actual markets
diverge substantially from the theoretical models. Price regulation is justified
by the so-called "market failures." Price regulation based on the cost of
production, the most traditional form of price control, has fallen into disuse in
favor of systems of international reference pricing and value-based pricing.
PMID- 25853830
TI - [Universal ethical principles and their application in clinical drug trials].
AB - Since 1931, and especially since the Nuremberg Code of 1947, an increasing number
of declarations, regulations, norms, guidelines, laws, resolutions, and rules
intended to create conditions for better protection of subjects participating in
research studies have been published, although some have meant setbacks in the
human rights of vulnerable populations. As such, violations of the dignity of
experimental subjects in clinical trials continue. What researchers investigate
and how the research is done, the quality and transparency of the data, and the
analysis and the publication of results (of both raw and processed data) respond
to the financial interests of the pharmaceutical companies, coming into permanent
tension with bioethical principles and the needs of society. The active
participation of civil society is necessary to make it so that pharmaceutical
research, results and applications subordinate economic benefits to the
protection of human rights.
PMID- 25853831
TI - [The impact of researchers loyal to Big Pharma on the ethics and quality of
clinical trials in Latin America].
AB - This article explains the difficulties innovative pharmaceutical firms have in
repaying shareholders with attractive dividends. The problem is the result of the
expiration of the patents of blockbuster drugs and the difficulties that the
firms have in bringing new blockbuster drugs to the market. One of the solutions
companies have found has been to accelerate the implementation of clinical trials
in order to expedite the commercialization of new drugs. Doing so increases the
period in which they can sell drugs at monopoly prices. We therefore discuss how
innovative pharmaceutical firms shorten the implementation time of clinical
trials in Latin America and the consequences such actions have on the quality of
the collected data, the protection of human rights of the subjects of
experimentation, and compliance with the ethical principles approved in
international declarations.
PMID- 25853832
TI - [Bioethical problems in researching new vaccines: do they respond to public
health reasons?].
AB - The ethical problems in vaccine research have grown in frequency and magnitude in
last decades, due to the dominant place of the pharmaceutical industry in the
development of such studies. Traditional issues of security and efficacy have
been aggravated by the conflicts of interests introduced by commercial
competition in a global market worth billions of dollars. We present here a few
examples in which the professional integrity of researchers, the moral
responsibility of sponsors, and the public regulation and control by national
States are put into question. The consequences of these changes represent serious
threats to the rights of people included in these studies as well as disputable
progress for public health.
PMID- 25853833
TI - [The use of placebos in phase III clinical trials in Brazil].
AB - In 2008, Brazil's Federal Council of Medicine [Conselho Federal de Medicina]
(CFM)--regulatory and supervisory agency on the ethical practice of medicine-
banned the participation of Brazilian doctors in studies using placebos for
diseases with efficient and effective treatment. This position differs with the
Helsinki Declaration, which allows the use of placebos in methodologically
justified conditions. To ascertain whether the CMF's ethical regulation modified
the use of placebos in phase III clinical trials in Brazil, characteristics of
the records in ClinicalTrials.gov were researched in the periods from 2003 to
2007 and from 2009 to 2013. The conclusions reached were: a) the regulations
issued by the CFM in 2008 were ineffective and the position adopted by the
Helsinki Declaration prevails; b) there was significant sponsorship by the
multinational pharmaceutical industry of trials with placebos; c) the research
was predominantly on new drugs for chronic diseases, with little study done of
the neglected diseases which are of great importance to Brazil.
PMID- 25853834
TI - [Antipsychotics for schizophrenia: the paradigm of psychiatric drugs].
AB - Antipsychotic drugs do not appear to reverse the causes of schizophrenia, and
although they can relieve symptoms in the short to medium term, in the long term
they may not be beneficial and could even be counterproductive. Their use should
be limited to acute situations in which agitation and tension is disabling. The
drugs have significant adverse effects, and given the refusal of a person to
continue taking them, a harm reduction strategy to support and monitor the
withdrawal may be preferable to coercion. There are alternatives to neuroleptics.
Prescribers should be more vigilant and consider the assessments of users
regarding the drugs' effects. Adherence to treatment guidelines is low, probably
because the guidelines are based on clinical trials of deficient quality which
consequently should be improved and extended over a greater period of time. The
root of the problem is likely the tautology on the etiology and biological nature
of what is known as schizophrenia, which in fact does not seem to be more than a
commercial and ideological construct.
PMID- 25853835
TI - Fear of negative evaluation biases social evaluation inference: evidence from a
probabilistic learning task.
AB - BACKGROUND: Fear of negative evaluation (FNE) defines social anxiety yet the
process of inferring social evaluation, and its potential role in maintaining
social anxiety, is poorly understood. We developed an instrumental learning task
to model social evaluation learning, predicting that FNE would specifically bias
learning about the self but not others. METHODS: During six test blocks (3 self
referential, 3 other-referential), participants (n = 100) met six personas and
selected a word from a positive/negative pair to finish their social evaluation
sentences "I think [you are / George is]...". Feedback contingencies corresponded
to 3 rules, liked, neutral and disliked, with P[positive word correct] = 0.8, 0.5
and 0.2, respectively. RESULTS: As FNE increased participants selected fewer
positive words (beta = -0.4, 95% CI -0.7, -0.2, p = 0.001), which was strongest
in the self-referential condition (FNE * condition 0.28, 95% CI 0.01, 0.54, p =
0.04), and the neutral and dislike rules (FNE * condition * rule, p = 0.07). At
low FNE the proportion of positive words selected for self-neutral and self
disliked greatly exceeded the feedback contingency, indicating poor learning,
which improved as FNE increased. CONCLUSIONS: FNE is associated with differences
in processing social-evaluative information specifically about the self. At low
FNE this manifests as insensitivity to learning negative self-referential
evaluation. High FNE individuals are equally sensitive to learning positive or
negative evaluation, which although objectively more accurate, may have
detrimental effects on mental health.
PMID- 25853837
TI - The economy of motion of the totally robotic gastric bypass: technique, learning
curve, and outcomes of a fellowship-trained, robotic bariatric surgeon.
AB - We present our technique for a totally robot-assisted laparoscopic Roux-en-Y
gastric bypass. Moreover, data are presented in relation to a single-surgeon
experience with use of the robotic platform in bariatric surgery. We reviewed a
single surgeon's console and room time from 2009 to 2013 for all robot-assisted
Roux-en-Y gastric bypasses (RARYGBs). Revision operations were excluded. There
were in total 168 robotic bariatric operations in this time frame. The number of
cases performed each year and the cumulative number of each operation were
considered as well. The change in console time as related to the number of cases
and the change in room time as related to the console time and number of cases
were investigated. Complications during this time and their frequency were noted
and described. The console time for RARYGB ranged from 131 +/- 46 minutes in 2010
to 94 +/- 29 minutes in 2013 (P<.05). There were in total 22 complications, for
an overall complication rate of 13.1%: four anastomotic strictures (2.4%), seven
marginal ulcerations (4.2%), two gastrointestinal bleeds (1.2%), five internal
hernias (3.0%), two abdominal pains requiring diagnostic laparoscopy (1.2%), and
two gastrointestinal leaks (1.2%). There were no deaths. In this series, the
console surgeon performed 168 RARYGBs and had a leak rate of 1.2% and a mortality
of 0% within the first 66 cases and a 0% leak rate over the next 102 cases. Thus,
we believe that the robot has a decreased caseload requirement to reach
proficiency with comparable outcomes versus both the hybrid and purely
laparoscopic approaches.
PMID- 25853838
TI - Self-assembly fabrication of hollow mesoporous silica@Co-Al layered double
hydroxide@graphene and application in toxic effluents elimination.
AB - Here, we propose a self-assembly process to prepare hierarchical HM-SiO2@Co-Al
LDH@graphene, with the purpose of combining their outstanding performance. Hollow
mesoporous silica was first synthesized as the core, using a novel sonochemical
method, followed by a controlled shell coating process and chemical reduction. As
a result of the electrostatic potential difference among HM-SiO2, Co-Al LDH, and
graphene oxide, the HM-SiO2 spheres were coated by Co-Al LDH and graphene.
Subsequently, the HM-SiO2@Co-Al LDH@graphene spheres were introduced into an
epoxy resin (EP) matrix for investigation of their toxic effluents capture and
elimination effectiveness during combustion. The amount of toxic CO and volatile
organic compounds from the epoxy resin decomposition significantly suppressed
after incorporating the HM-SiO2@Co-Al LDH@graphene hybrids, implying a reduced
toxicity.
PMID- 25853836
TI - Antiplatelet therapy discontinuation and the risk of serious cardiovascular
events after coronary stenting: observations from the CREDO-Kyoto Registry Cohort
2.
AB - Relation of antiplatelet therapy (APT) discontinuation with the risk of serious
cardiovascular events has not been fully addressed yet. This study is aimed to
evaluate the risk of ischemic event after APT discontinuation based on long-term
APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939
consecutive patients undergoing first coronary revascularization, 10470 patients
underwent percutaneous coronary intervention either with bare-metal stents (BMS)
only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of
patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus
24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT
status (dual-, single- and no-APT) and linked the adverse events to the APT
status just 1-day before the events. No-APT as compared with dual- or single-APT
was associated with significantly higher risk for stent thrombosis (ST) beyond 1
month after SES implantation (cumulative incidence rates beyond 1-month: 1.23
versus 0.15/0.29, P<0.001/P<0.001), while higher risk of no-APT for ST was
evident only until 6-month after BMS implantation (incidence rates between 1- and
6-month: 8.43 versus 0.71/1.20, P<0.001/P<0.001, and cumulative incidence rates
beyond 6-month: 0.31 versus 0.11/0.08, P=0.16/P=0.08). No-APT as compared with
dual- or single-APT was also associated with significantly higher risk for
spontaneous myocardial infarction (MI) and stroke regardless of the types of
stents implanted. Single-APT as compared with dual-APT was not associated with
higher risk for serious adverse events, except for the marginally higher risk for
ST in the SES stratum. In conclusion, discontinuation of both aspirin and
thienopyridines was associated with increased risk for serious cardiovascular
events including ST, spontaneous MI and stroke beyond 1-month after coronary
stenting.
PMID- 25853839
TI - Correction to "Initial Events in the Degradation of Hyaluronan Catalyzed by
Hyaluronate Lyase from Streptococcus pneumoniae: QM/MM Simulation".
PMID- 25853840
TI - Engineering Escherichia coli into a protein delivery system for mammalian cells.
AB - Many Gram-negative pathogens encode type 3 secretion systems, sophisticated
nanomachines that deliver proteins directly into the cytoplasm of mammalian
cells. These systems present attractive opportunities for therapeutic protein
delivery applications; however, their utility has been limited by their inherent
pathogenicity. Here, we report the reengineering of a laboratory strain of
Escherichia coli with a tunable type 3 secretion system that can efficiently
deliver heterologous proteins into mammalian cells, thereby circumventing the
need for virulence attenuation. We first introduced a 31 kB region of Shigella
flexneri DNA that encodes all of the information needed to form the secretion
nanomachine onto a plasmid that can be directly propagated within E. coli or
integrated into the E. coli chromosome. To provide flexible control over type 3
secretion and protein delivery, we generated plasmids expressing master
regulators of the type 3 system from either constitutive or inducible promoters.
We then constructed a Gateway-compatible plasmid library of type 3 secretion
sequences to enable rapid screening and identification of sequences that do not
perturb function when fused to heterologous protein substrates and optimized
their delivery into mammalian cells. Combining these elements, we found that
coordinated expression of the type 3 secretion system and modified target protein
substrates produces a nonpathogenic strain that expresses, secretes, and delivers
heterologous proteins into mammalian cells. This reengineered system thus
provides a highly flexible protein delivery platform with potential for future
therapeutic applications.
PMID- 25853842
TI - Preduodenal superior mesenteric vein and Whipple procedure with vascular
reconstruction-A case report.
AB - INTRODUCTION: Portal vein (PV) disorders are various, but rare. Here, we report a
preduodenal superior mesenteric vein (PDSMV) in a patient who underwent a
pancreaticoduodenectomy. PRESENTATION OF CASE: A 67-year old woman with familial
adenomatosis polyposis was suspicious for cancer of the papilla of vater and
scheduled for surgery. Pre-operative diagnostic revealed a PDSMV continuing into
the left PV. The splenic vein (SV) continued directly into the right PV without
forming ananatomic PV confluence. Eight centimetre of the PDSMV were resected
during the pancreaticoduodenectomy and reconnected using a
polytetrafluoroethylene prosthesis. On day 1, early graft thrombosis was treated
by thrombectomy and change to a larger graft. Pathology confirmed a R0-resection
of the adenocarcinoma of the papilla of vater (pTis pN0,G2). At three-month
follow-up, the patient was cancer-free and clinically asymptomatic, although, a
late graft thrombosis with accompanying newly build venous collaterals passing
mesenteric blood to the SV were found. DISCUSSION: Rare PV disorders like a PDSMV
do not contradict pancreatic surgery, but should be treated in experienced
centres. Skills of SMV/PV reconstruction and its peri-operative management might
be beneficial for successful outcome. Despite late graft thrombosis no clinical
disadvantage occurred most likely due to preservation of the SV and of potential
venous collateral pathways. CONCLUSION: Extended surgical procedures like a
pancreaticoduodenectomy are realisable in patients with PV disorders, but require
awareness, adequate radiological interpretation and specific surgical experience
for secure treatment.
PMID- 25853841
TI - Cardio-ankle vascular index is associated with cardiovascular target organ damage
and vascular structure and function in patients with diabetes or metabolic
syndrome, LOD-DIABETES study: a case series report.
AB - BACKGROUND: The cardio ankle vascular index (CAVI) is a new index of the overall
stiffness of the artery from the origin of the aorta to the ankle. This index can
estimate the risk of atherosclerosis. We aimed to find the relationship between
CAVI and target organ damage (TOD), vascular structure and function, and
cardiovascular risk factors in Caucasian patients with type 2 diabetes mellitus
or metabolic syndrome. METHODS: We included 110 subjects from the LOD-Diabetes
study, whose mean age was 61 +/- 11 years, and 37.3% were women. Measurements of
CAVI, brachial ankle pulse wave velocity (ba-PWV), and ankle brachial index (ABI)
were taken using the VaSera device. Cardiovascular risk factors, renal function
by creatinine, glomerular filtration rate, and albumin creatinine index were also
obtained, as well as cardiac TOD with ECG and vascular TOD and carotid intima
media thickness (IMT), carotid femoral PWV (cf-PWV), and the central and
peripheral augmentation index (CAIx and PAIx). The Framingham-D'Agostino scale
was used to measure cardiovascular risk. RESULTS: Mean CAVI was 8.7 +/- 1.3. More
than half (54%) of the participants showed one or more TOD (10% cardiac, 13%
renal; 48% vascular), and 13% had ba-PWV >= 17.5 m/s. Patients with any TOD had
the highest CAVI values: 1.15 (CI 95% 0.70 to 1.61, p < 0.001) and 1.14 (CI 95%
0.68 to 1.60, p < 0.001) when vascular TOD was presented, and 1.30 (CI 95% 0.51
to 2.10, p = 0.002) for the cardiac TOD. The CAVI values had a positive
correlation with HbA1c and systolic and diastolic blood pressure, and a negative
correlation with waist circumference and body mass index. The positive
correlations of CAVI with IMT (beta = 0.29; p < 0.01), cf-PWV (beta = 0.83; p <
0.01), ba-PWV (beta = 2.12; p < 0.01), CAIx (beta = 3.42; p < 0.01), and PAIx
(beta = 5.05; p = 0.04) remained after adjustment for cardiovascular risk, body
mass index, and antihypertensive, lipid-lowering, and antidiabetic drugs.
CONCLUSIONS: The results of this study suggest that the CAVI is positively
associated with IMT, cf-PWV, ba-PWV, CAIx, and PAIx, regardless of cardiovascular
risk and the drug treatment used. Patients with cardiovascular TOD have higher
values of CAVI. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01065155.
PMID- 25853843
TI - Tailgut cyst: A case report and literature review.
AB - INTRODUCTION: Tailgut cysts are rare diseases but can be challenging to manage.
PRESENTATION OF CASE: This is a case report of a tailgut cyst, in a 42 year old
female. The cyst was incidentally detected on imaging, and treated with Kraske
surgical approach. DISCUSSION: Hereby, we review the relevant information present
in the medical literature about the incidence, methods of diagnosis, treatment
options and management plans. CONCLUSION: Surgical management should be tailored
individually for each patient, based on the advantages and disadvantages of each
surgical approach.
PMID- 25853844
TI - Obscure gastrointestinal bleeding due to multifocal intestinal angiosarcoma.
AB - INTRODUCTION: Intestinal angiosarcomas are an extremely rare and aggressive
vascular tumors, with a few cases reported in the literature. PRESENTATION OF
CASE: A 45 years-old male arrived to our hospital with intermittent
gastrointestinal bleeding presenting melena and weight loss, he has antecedent of
pelvic radiotherapy ten years before admission for an unknown pelvic tumor.
Emergency surgery was required because of uncontrolled bleeding and hemodynamic
instability. Histopathological findings revealed a multifocal high-grade
epithelioid angiosarcoma, with cells reactive for CD31, keratins CKAE 1/AE3 and
factor VIII. DISCUSSION: Angiosarcomas are aggressive tumors with a high rate of
lymph node metastasis and peripheral organs. The diagnosis is difficult because
it present nonspecific clinical presentation, radiological and histopathological
findings. There are few reports of angiosarcoma involving the small intestine and
the most common presentation are abdominal pain and gastrointestinal bleeding.
There is not enough information for intestinal angiosarcoma secondary to
radiation therapy, but there have been proposed criteria for diagnosis: no
microscopic or clinical evidence of antecedent malignant lesion, angiosarcoma
presented in the field of irradiation, long latency period between radiation and
angiosarcoma and histological confirmation. We suspect our patient course with a
secondary form of angiosarcoma. Therapy for bleeding angiosarcoma consists in
control of bleeding and medical management to stabilize the patient. Once
accomplished surgical resection is required. CONCLUSION: We should keep in mind
this tumors as a cause of obscure intestinal bleeding in patients with medical
history of radiation therapy.
PMID- 25853845
TI - Transoral surgery for oropharyngeal tumors using the Medrobotics((r)) Flex((r))
System - a case report.
AB - INTRODUCTION: Transoral resection of pharyngeal tumors with acceptable
oncological and functional results can be challenging due to their location in a
narrow anatomic space. CASE PRESENTATION: In this case report, we demonstrate
successful visualization and resection of a squamous cell carcinoma of the
oropharynx using the novel Medrobotics((r)) Flex((r)) System. The
Medrobotics((r)) Flex((r)) System (Medrobotics Corp., Raynham, MA, USA) is an
operator controlled flexible endoscope system that includes a rigid endoscope and
computer-assisted controllers, with two external channels for the use of
compatible, 3.5mm flexible instruments. DISCUSSION: In a 74-year old female
patient a T1 squamous cell carcinoma of the oropharynx was visualized and
completely resected using this system. The Medrobotics((r)) Flex((r)) System is a
promising device for transoral approaches in resection of tumors within the
pharynx. CONCLUSION: Good visualization, access, and flexibility of the endoscope
and instruments are hereby clear advantages of the system compared to commonly
used systems.
PMID- 25853846
TI - A facile solvothermal growth of single crystal mixed halide perovskite
CH3NH3Pb(Br(1-x)Cl(x))3.
AB - We demonstrate a facile synthetic approach for preparing mixed halide perovskite
(CH3NH3)Pb(Br1-xClx)3 single crystals by the solvothermal growth of
stoichiometric PbBr2 and [(1 - y)CH3NH3Br + yCH3NH3Cl] DMF precursor solutions.
The band gap of (CH3NH3)Pb(Br1-xClx)3 single crystals increased and the unit cell
dimensions decreased with an increase in Cl content x, consistent with previous
theoretical predictions. Interestingly, the Cl/Br ratio in the (CH3NH3)Pb(Br1
xClx)3 single crystals is larger than that of the precursor solution, suggesting
an unusual crystal growth mechanism.
PMID- 25853848
TI - Association of APC, GSTP1 and SOCS1 promoter methylation with the risk of
hepatocellular carcinoma: a meta-analysis.
AB - Studies of the relationships of adenomatous polyposis coli (APC), glutathione-S
transferase P1 (GSTP1) and suppressor of the cytokine signalling 1 (SOCS1)
promoter region methylation with the risk of hepatocellular carcinoma (HCC) have
yielded inconsistent results. We carried out the current meta-analysis to
comprehensively assess the associations between APC, GSTP1 and SOCS1 promoter
methylation frequency and the risk of HCC. All relevant reports were identified
by searching the PubMed, Embase, Web of Science, CNKI and the Chinese BioMedical
Literature databases before 1 March 2014, with restriction to articles published
in the Chinese and English languages. Pooled odds ratios (ORs) and corresponding
95% confidence intervals (CIs) were calculated to investigate the rates of APC,
GSTP1 and SOCS1 promoter methylation and the risk of HCC. Our meta-analysis
identified relationships of APC (12 studies with 592 HCC tumour tissues), GSTP1
(14 studies including 646 HCC tumour tissues) and SOCS1 (11 studies with 512 HCC
tumour tissues) promoter methylation with the risk of HCC. Compared with
paracancerous tissues, the pooled ORs of APC, GSTP1 and SOCS1 promoter region
methylation in HCC cancer tissues were 5.32 (95% CI=2.96-9.56), 5.65, (95%
CI=3.41-9.35) and 2.73 (95% CI=1.37-5.44), respectively. Compared with normal
liver tissues as controls, the pooled ORs of APC, GSTP1 and SOCS1 promoter region
methylation in HCC cancer tissues were 20.43 (95% CI=5.56-75.08), 18.78 (95%
CI=5.76-61.19) and 13.00 (95% CI=5.20-32.47), respectively. Subgroup analysis by
ethnicity showed that APC, GSTP1 and SOCS1 promoter methylation was associated
significantly with the risk of HCC in both Asian and White populations (all
P<0.05). Our meta-analysis suggested strong associations between APC, GSTP1 and
SOCS1 gene promoter methylation and the risk of HCC, suggesting these to be
promising biomarkers for HCC.
PMID- 25853847
TI - Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute
intestinal inflammation in mice.
AB - Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal
innate and adaptive immune responses. Factors such as genetic, microbial and
environmental are involved in the development of these disorders. Accordingly,
animal models that mimic human diseases are tools for the understanding the
immunological processes of the IBD as well as to evaluate new therapeutic
strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus
snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the
modulatory effect of CTX in a murine model of colitis induced by 2,4,6-
trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally
18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX
administration resulted in decreased weight loss, disease activity index (DAI),
macroscopic tissue damage, histopathological score and myeloperoxidase (MPO)
activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of
TNF-alpha, IL-1beta and IL-6 were lower in colon tissue homogenates of TNBS-mice
that received the CTX when compared with untreated TNBS mice. The analysis of
distinct cell populations obtained from the intestinal lamina propria showed that
CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17
population; CTX decreased IL-17 secretion but did not alter the frequency of
CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased
CD4+FoxP3+ cell population as well as secretion of TGF-beta, prostaglandin E2
(PGE2) and lipoxin A4 (LXA4) was observed in TNBS-colitis mice treated with CTX
compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to
modulate the intestinal acute inflammatory response induced by TNBS, resulting in
the improvement of clinical status of the mice. This effect of CTX is complex and
involves the suppression of the pro-inflammatory environment elicited by
intrarectal instillation of TNBS due to the induction of a local anti
inflammatory profile in mice.
PMID- 25853850
TI - High-resolution genomic analysis: the tumor-immune interface comes into focus.
AB - A genomic analysis of heterogeneous colorectal tumor samples has uncovered
interactions between immunophenotype and various aspects of tumor biology, with
implications for informing the choice of immunotherapies for specific patients
and guiding the design of personalized neoantigen-based vaccines.
PMID- 25853849
TI - SaeRS-dependent inhibition of biofilm formation in Staphylococcus aureus Newman.
AB - The SaeRS two-component regulatory system of Staphylococcus aureus is known to
affect the expression of many genes. The SaeS protein is the histidine kinase
responsible for phosphorylation of the response regulator SaeR. In S. aureus
Newman, the sae system is constitutively expressed due to a point mutation in
saeS, relative to other S. aureus strains, which results in substitution of
proline for leucine at amino acid 18. Strain Newman is unable to form a robust
biofilm and we report here that the biofilm-deficient phenotype is due to the
saeSP allele. Replacement of the Newman saeSP with saeSL, or deletion of saeRS,
resulted in a biofilm-proficient phenotype. Newman culture supernatants were
observed to inhibit biofilm formation by other S. aureus strains, but did not
affect biofilm formation by S. epidermidis. Culture supernatants of Newman saeSL
or Newman DeltasaeRS had no significant effect on biofilm formation. The
inhibitory factor was inactivated by incubation with proteinase K, but survived
heating, indicating that the inhibitory protein is heat-stable. The inhibitory
protein was found to affect the attachment step in biofilm formation, but had no
effect on preformed biofilms. Replacement of saeSL with saeSP in the biofilm
proficient S. aureus USA300 FPR3757 resulted in the loss of biofilm formation.
Culture supernatants of USA300 FPR3757 saeSP, did not inhibit biofilm formation
by other staphylococci, suggesting that the inhibitory factor is produced but not
secreted in the mutant strain. A number of biochemical methods were utilized to
isolate the inhibitory protein. Although a number of candidate proteins were
identified, none were found to be the actual inhibitor. In an effort to reduce
the number of potential inhibitory genes, RNA-Seq analyses were done with wild
type strain Newman and the saeSL and DeltasaeRS mutants. RNA-Seq results
indicated that sae regulates many genes that may affect biofilm formation by
Newman.
PMID- 25853851
TI - Tether-directed bisfunctionalization reactions of c60 and c70.
AB - Four easily isolable regio- and stereoselective bis-adducts of C60 and C70 , as
well as a new C70 -dumbbell derivative, have been synthesized by using two
different bismalonate tethered moieties. The derivatives that possess relatively
long-tethered moieties show highly symmetric addition patterns, as evidenced by
spectroscopic measurements, whereas the derivatives possessing the shorter
tethered moiety exhibit interesting addition patterns on C60 and C70 .
PMID- 25853852
TI - Increased biodiversity in the environment improves the humoral response of rats.
AB - Previous studies have compared the immune systems of wild and of laboratory
rodents in an effort to determine how laboratory rodents differ from their
naturally occurring relatives. This comparison serves as an indicator of what
sorts of changes might exist between modern humans living in Western culture
compared to our hunter-gatherer ancestors. However, immunological experiments on
wild-caught animals are difficult and potentially confounded by increased levels
of stress in the captive animals. In this study, the humoral immune responses of
laboratory rats in a traditional laboratory environment and in an environment
with enriched biodiversity were examined following immunization with a panel of
antigens. Biodiversity enrichment included colonization of the laboratory animals
with helminths and co-housing the laboratory animals with wild-caught rats.
Increased biodiversity did not apparently affect the IgE response to peanut
antigens following immunization with those antigens. However, animals housed in
the enriched biodiversity setting demonstrated an increased mean humoral response
to T-independent and T-dependent antigens and increased levels of "natural"
antibodies directed at a xenogeneic protein and at an autologous tissue extract
that were not used as immunogens.
PMID- 25853853
TI - Ultrastrong Mode Confinement in ZnO Surface Plasmon Nanolasers.
AB - Nanolasers with an ultracompact footprint can provide high-intensity coherent
light, which can be potentially applied to high-capacity signal processing,
biosensing, and subwavelength imaging. Among various nanolasers, those with
cavities surrounded by metals have been shown to have superior light emission
properties because of the surface plasmon effect that provides enhanced field
confinement capability and enables exotic light-matter interaction. In this
study, we demonstrated a robust ultraviolet ZnO nanolaser that can operate at
room temperature by using silver to dramatically shrink the mode volume. The
nanolaser shows several distinct features including an extremely small mode
volume, a large Purcell factor, and a slow group velocity, which ensures strong
interaction with the exciton in the nanowire.
PMID- 25853854
TI - Correction: thermodynamics of random reaction networks.
AB - [This corrects the article DOI: 10.1371/journal.pone.0117312.].
PMID- 25853855
TI - Investigation of genes encoding calcineurin B-like protein family in legumes and
their expression analyses in chickpea (Cicer arietinum L.).
AB - Calcium ion (Ca2+) is a ubiquitous second messenger that transmits various
internal and external signals including stresses and, therefore, is important for
plants' response process. Calcineurin B-like proteins (CBLs) are one of the plant
calcium sensors, which sense and convey the changes in cytosolic Ca2+
concentration for response process. A search in four leguminous plant (soybean,
Medicago truncatula, common bean and chickpea) genomes identified 9 to 15 genes
in each species that encode CBL proteins. Sequence analyses of CBL peptides and
coding sequences (CDS) suggested that there are nine original CBL genes in these
legumes and some of them were multiplied during whole genome or local gene
duplication. Coding sequences of chickpea CBL genes (CaCBL) were cloned from
their cDNAs and sequenced, and their annotations in the genome assemblies were
corrected accordingly. Analyses of protein sequences and gene structures of CBL
family in plant kingdom indicated its diverse origin but showed a remarkable
conservation in overall protein structure with appearance of complex gene
structure in the course of evolution. Expression of CaCBL genes in different
tissues and in response to different stress and hormone treatment were studied.
Most of the CaCBL genes exhibited high expression in flowers. Expression profile
of CaCBL genes in response to different abiotic stresses and hormones related to
development and stresses (ABA, auxin, cytokinin, SA and JA) at different time
intervals suggests their diverse roles in development and plant defence in
addition to abiotic stress tolerance. These data not only contribute to a better
understanding of the complex regulation of chickpea CBL gene family, but also
provide valuable information for further research in chickpea functional
genomics.
PMID- 25853856
TI - Singing from the grave: DNA from a 180 year old type specimen confirms the
identity of Chrysoperla carnea (Stephens).
AB - Historically serving as repositories for morphologically-based taxonomic
research, natural history collections are now increasingly being targeted in
studies utilizing DNA data. The development of advanced molecular techniques has
facilitated extraction of useable DNA from old specimens, including type
material. Sequencing diagnostic molecular markers from type material enables
accurate species designation, especially where modern taxonomic hypotheses
confirm morphologically cryptic species complexes. One such example is
Chrysoperla carnea (Stephens), which belongs to a complex of about 20 cryptic
species, most of which can only be reliably distinguished by their pre-mating
courtship songs or by DNA analysis. The subtle morphological variation in the
group has led to disagreement over the previous designation of the lectotype for
C. carnea, an issue that has been further compounded because Chrysoperla carnea
is a highly valued biological control agent in arable crops. Archival DNA
extraction and sequencing from the 180 year old lectotype specimen, combined with
Bayesian and Likelihood based phylogenetic analyses of modern specimens from the
entire complex, were used to establish unambiguously the true identity of
Chrysoperla carnea.
PMID- 25853857
TI - Single administration of ultra-low-dose lipopolysaccharide in rat early pregnancy
induces TLR4 activation in the placenta contributing to preeclampsia.
AB - Balanced immune responses are essential for the maintenance of successful
pregnancy. Aberrant responses of immune system during pregnancy increase the risk
of preeclampsia. Toll-like receptor 4 (TLR4) plays a crucial role in the
activation of immune system at the maternal-fetal interface. This study aimed to
generate a rat model of preeclampsia by lipopolysaccharide (LPS, a TLR4 agonist)
administration on gestational day (GD) 5 as rats are subjected to placentation
immediately after implantation between GDs 4 and 5, and to assess the
contribution of TLR4 signaling to the development of preeclampsia. Single
administration of 0.5 MUg/kg LPS significantly increased blood pressure of
pregnant rats since GD 6 (systolic blood pressure, 124.89 +/- 1.79 mmHg versus
119.02 +/- 1.80 mmHg, P < 0.05) and urinary protein level since GD 9 (2.02 +/-
0.29 mg versus 1.11 +/- 0.18 mg, P < 0.01), but barely affected blood pressure or
proteinuria of virgin rats compared with those of saline-treated pregnant rats.
This was accompanied with adverse pregnancy outcomes including fetal growth
restriction. The expression of TLR4 and NF-kappaB p65 were both increased in the
placenta but not the kidney from LPS-treated pregnant rats, with deficient
trophoblast invasion and spiral artery remodeling. Furthermore, the levels of
inflammatory cytokines were elevated systemically and locally in the placenta
from pregnant rats treated with LPS. TLR4 signaling in the placenta was
activated, to which that in the placenta of humans with preeclampsia changed
similarly. In conclusion, LPS administration to pregnant rats in early pregnancy
could elicit TLR4-mediated immune response at the maternal-fetal interface
contributing to poor early placentation that may culminate in the preeclampsia
like syndrome.
PMID- 25853858
TI - Metabolomic method: UPLC-q-ToF polar and non-polar metabolites in the healthy rat
cerebellum using an in-vial dual extraction.
AB - Unbiased metabolomic analysis of biological samples is a powerful and
increasingly commonly utilised tool, especially for the analysis of bio-fluids to
identify candidate biomarkers. To date however only a small number of metabolomic
studies have been applied to studying the metabolite composition of tissue
samples, this is due, in part to a number of technical challenges including
scarcity of material and difficulty in extracting metabolites. The aim of this
study was to develop a method for maximising the biological information obtained
from small tissue samples by optimising sample preparation, LC-MS analysis and
metabolite identification. Here we describe an in-vial dual extraction (IVDE)
method, with reversed phase and hydrophilic liquid interaction chromatography
(HILIC) which reproducibly measured over 4,000 metabolite features from as little
as 3mg of brain tissue. The aqueous phase was analysed in positive and negative
modes following HILIC separation in which 2,838 metabolite features were
consistently measured including amino acids, sugars and purine bases. The non
aqueous phase was also analysed in positive and negative modes following reversed
phase separation gradients respectively from which 1,183 metabolite features were
consistently measured representing metabolites such as phosphatidylcholines,
sphingolipids and triacylglycerides. The described metabolomics method includes a
database for 200 metabolites, retention time, mass and relative intensity, and
presents the basal metabolite composition for brain tissue in the healthy rat
cerebellum.
PMID- 25853859
TI - Synchronous rhythmic interaction enhances children's perceived similarity and
closeness towards each other.
AB - Inter-personal synchronization is important for performing many cooperative
tasks. Notably, synchrony has also been shown to have considerable positive
social influences, possibly mediated by synchrony-induced changes in social
attitude such as an increased sense of similarity and affiliation between
interacting individuals. This effect has been demonstrated in adults, but it is
unknown whether synchrony might have a similar impact on the social attitudes of
children. We thus set to directly examine the influence of synchronous rhythmic
interaction on perceived similarity and closeness in pairs of 8-9 year old
children. We found that children who had participated in a synchronous
interaction regarded their interacting partner as more similar and closer to
themselves than children who had not interacted at all or who had taken part in
an asynchronous interaction. These findings reveal that synchronous interaction
can positively alter social attitudes between interacting children, suggesting a
potential mechanism by which synchrony may enhance positive social interaction
through attitudinal shift.
PMID- 25853861
TI - Correction: Abiotic racemization kinetics of amino acids in marine sediments.
PMID- 25853860
TI - Immunophenotyping of Waldenstroms macroglobulinemia cell lines reveals distinct
patterns of surface antigen expression: potential biological and therapeutic
implications.
AB - Waldenstroms macroglobulinemia (WM) is a subtype of Non-Hodgkin's lymphoma in
which the tumor cell population is markedly heterogeneous, consisting of
immunoglobulin-M secreting B-lymphocytes, plasmacytoid lymphocytes and plasma
cells. Due to rarity of disease and scarcity of reliable preclinical models, many
facets of WM molecular and phenotypic architecture remain incompletely
understood. Currently, there are 3 human WM cell lines that are routinely used in
experimental studies, namely, BCWM.1, MWCL-1 and RPCI-WM1. During establishment
of RPCI-WM1, we observed loss of the CD19 and CD20 antigens, which are typically
present on WM cells. Intrigued by this observation and in an effort to better
define the immunophenotypic makeup of this cell line, we conducted a more
comprehensive analysis for the presence or absence of other cell surface antigens
that are present on the RPCI-WM1 model, as well as those on the two other WM cell
lines, BCWM.1 and MWCL-1. We examined expression of 65 extracellular and 4
intracellular antigens, comprising B-cell, plasma cell, T-cell, NK-cell, myeloid
and hematopoietic stem cell surface markers by flow cytometry analysis. RPCI-WM1
cells demonstrated decreased expression of CD19, CD20, and CD23 with enhanced
expression of CD28, CD38 and CD184, antigens that were differentially expressed
on BCWM.1 and MWCL-1 cells. Due to increased expression of CD184/CXCR4 and CD38,
RPCI-WM1 represents a valuable model in which to study the effects anti-CXCR4 or
anti-CD38 targeted therapies that are actively being developed for treatment of
hematologic cancers. Overall, differences in surface antigen expression across
the 3 cell lines may reflect the tumor clone population predominant in the index
patients, from whom the cell lines were developed. Our analysis defines the
utility of the most commonly employed WM cell lines as based on their
immunophenotype profiles, highlighting unique differences that can be further
studied for therapeutic exploit.
PMID- 25853862
TI - Peripheral opioid antagonist enhances the effect of anti-tumor drug by blocking a
cell growth-suppressive pathway in vivo.
AB - The dormancy of tumor cells is a major problem in chemotherapy, since it limits
the therapeutic efficacy of anti-tumor drugs that only target dividing cells. One
potential way to overcome chemo-resistance is to "wake up" these dormant cells.
Here we show that the opioid antagonist methylnaltrexone (MNTX) enhances the
effect of docetaxel (Doc) by blocking a cell growth-suppressive pathway. We found
that PENK, which encodes opioid growth factor (OGF) and suppresses cell growth,
is predominantly expressed in diffuse-type gastric cancers (GCs). The blockade of
OGF signaling by MNTX releases cells from their arrest and boosts the effect of
Doc. In comparison with the use of Doc alone, the combined use of Doc and MNTX
significantly prolongs survival, alleviates abdominal pain, and diminishes Doc
resistant spheroids on the peritoneal membrane in model mice. These results
suggest that blockade of the pathways that suppress cell growth may enhance the
effects of anti-tumor drugs.
PMID- 25853863
TI - Glucocorticoids suppress GLP-1 secretion: possible contribution to their
diabetogenic effects.
AB - Evidence indicates that subtle abnormalities in GC (glucocorticoid) plasma
concentrations and/or in tissue sensitivity to GCs are important in the metabolic
syndrome, and it is generally agreed that GCs induce insulin resistance. In
addition, it was recently reported that short-term exposure to GCs reduced the
insulinotropic effects of the incretin GLP-1 (glucagon-like peptide 1). However,
although defective GLP-1 secretion has been correlated with insulin resistance,
potential direct effects of GCs on GLP-1-producing L-cell function in terms of
GLP-1 secretion and apoptosis have not been studied in any greater detail. In the
present study, we sought to determine whether GCs could exert direct effects on
GLP-1-producing L-cells in terms of GLP-1 secretion and cell viability. We
demonstrate that the GR (glucocorticoid receptor) is expressed in GLP-1-producing
cells, where GR activation in response to dexamethasone induces SGK1 (serum- and
glucocorticoid-inducible kinase 1) expression, but did not influence
preproglucagon expression or cell viability. In addition, dexamethasone treatment
of enteroendocrine GLUTag cells reduced GLP-1 secretion induced by glucose, 2
deoxy-D-glucose, fructose and potassium, whereas the secretory response to a
phorbol ester was unaltered. Furthermore, in vivo administration of dexamethasone
to rats reduced the circulating levels of GLP-1 concurrent with induction of
insulin resistance and glucose intolerance. We can conclude that GR activation in
GLP-1-producing cells will diminish the secretory responsiveness of these cells
to subsequent carbohydrate stimulation. These effects may not only elucidate the
pathogenesis of steroid diabetes, but could ultimately contribute to the
identification of novel molecular targets for controlling incretin secretion.
PMID- 25853864
TI - TDP-43 as a possible biomarker for frontotemporal lobar degeneration: a
systematic review of existing antibodies.
AB - Frontotemporal lobar degeneration (FTLD) is one of the leading causes of dementia
after Alzheimer's disease. A high-ranking candidate to become a diagnostic marker
for a major pathological subtype of FTLD is the transactive response DNA binding
protein of 43 kDa (TDP-43). The main objective is to elucidate which antibodies
are specific for pathological TDP-43, with special interest in its modified
isoforms. Indeed, TDP-43 has been shown to be hyperphosphorylated and truncated
in disease. A secondary objective is to review existing immunoassays that
quantify TDP-43 in biofluids. A systematic review of literature was performed by
searching PubMed and Web of Science using predefined keywords. Of considered
research papers the methods section was reviewed to select publications that
enabled us to answer our learning objective. After quality assessment, antibody
characteristics and related outcomes were extracted. We identified a series of
well-characterized antibodies based on a scoring system that assessed the ability
of each antibody to detect TDP-43 pathology. A selection of 29 unique antibodies
was made comprising 10 high-ranking antibodies which were reported multiple times
to detect TDP-43 pathology in both immunostaining and immunoblotting experiments
and 19 additional antibodies which detected TDP-43 pathology but were only scored
once. This systematic review provides an overview of antibodies that are reported
to detect pathological TDP-43. These antibodies can be used in future studies of
TDP-43 proteinopathies. Additionally, selected antibodies hold the potential to
be used in the development of novel immunoassays for the quantification of TDP-43
in biofluids, as a possible biomarker for FTLD-TDP.
PMID- 25853865
TI - Delay of Surgery for Melanoma Among Medicare Beneficiaries.
AB - IMPORTANCE: Timely delivery of surgery for cancer affects health care quality and
outcomes. However, population-based studies characterizing the delay of surgery
for melanoma in the United States have not been performed. OBJECTIVE: To assess
the delay of surgery for melanoma by tumor-, patient-, and physician-level
characteristics. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective
cohort study of Medicare beneficiaries diagnosed as having melanoma from January
1, 2000, through December 31, 2009, using the Surveillance, Epidemiology, and End
Results-Medicare database. We included all patients undergoing surgical excision
of melanoma diagnosed by means of results of skin biopsy. EXPOSURES: Anatomic
location and stage of the tumor, patient sociodemographic characteristics, prior
melanoma, Elixhauser comorbidities, and the specialties of the physicians who
performed the biopsy and surgery. MAIN OUTCOMES AND MEASURES: Surgical delay,
measured as the time from the biopsy to surgical excision. We estimated risk
adjusted odds ratios (ORs) and marginal probabilities of delay with 95% CIs for
each covariate using mixed-effects logistic regression. RESULTS: Our cohort
consisted of 32 501 cases of melanoma. Most of the patients were white (95.4%),
male (63.1%), married (47.9%), and 75 years or older (60.8%) and did not have a
prior melanoma (93.7%). Melanomas were most frequently located on the head and
neck (40.5%) and staged as in situ disease (48.2%). More than three-quarters of
cases (25 269 [77.7%]) underwent excision within 1.5 months of biopsy. Among
those treated after 1.5 months (7232 [22.3%]), 2620 (8.1% of all cases)
experienced a delay of longer than 3 months. The incidence of a risk-adjusted
surgical delay longer than 1.5 months was significantly increased among patients
85 years or older compared with those younger than 65 years (odds ratio [OR],
1.28 [95% CI, 1.05-1.55]; P = .02), those with a prior melanoma (OR, 1.20 [95%
CI, 1.08-1.34]; P = .001), and those with an increased comorbidity burden (OR,
1.18 [95% CI, 1.09-1.27]; P < .001). Melanomas that underwent biopsy and excision
by dermatologists had the lowest likelihood of delay (probability, 16% [95% CI,
14%-18%]). The highest likelihood of delay (probability, 31% [95% CI, 24%-37%])
occurred when the biopsy was performed by a nondermatologist and excised by a
primary care physician. Similar findings were observed for a delay longer than 3
months. CONCLUSIONS AND RELEVANCE: Approximately 1 in 5 Medicare beneficiaries
experience a delay of surgery for melanoma that is longer than 1.5 months. Those
patients undergoing biopsy and surgery by dermatologists have the lowest risk for
delay, highlighting potential opportunities for improved access to and
coordination of dermatologic care.
PMID- 25853866
TI - Identification and fine mapping of nuclear and nucleolar localization signals
within the human ribosomal protein S17.
AB - Human ribosomal protein S17 (RPS17) is mutated in Diamond-Blackfan Anemia (DBA),
a bone marrow disorder that fails to produce sufficient red blood cells leading
to anemia. Recently, an RPS17 protein sequence was also found to be naturally
inserted in the genome of hepatitis E virus (HEV) from patients chronically
infected by HEV. The role of RPS17 in HEV replication and pathogenesis remains
unknown due to the lack of knowledge about how RPS17 functions at a molecular
level. Understanding the biological function of RPS17 is critical for elucidating
its role in virus infection and DBA disease processes. In this study we probed
the subcellular distribution of normal and mutant RPS17 proteins in a human liver
cell line (Huh7). RPS17 was primarily detected within the nucleus, and more
specifically within the nucleoli. Using a transient expression system in which
RPS17 or truncations were expressed as fusions with enhanced yellow fluorescent
protein (eYFP), we were able to identify and map, for the first time, two
separate nuclear localization signals (NLSs), one to the first 13 amino acids of
the amino-terminus of RPS17 and the other within amino acids 30-60. Additionally,
we mapped amino acid sequences required for nucleolar accumulation of RPS17 to
amino acids 60-70. Amino acids 60-70 possess a di-RG motif that may be necessary
for nucleolar retention of RPS17. The results from this study enhance our
knowledge of RSP17 and will facilitate future mechanistic studies about the roles
of RSP17 in hepatitis E and DBA disease processes.
PMID- 25853867
TI - Inhaled nitric oxide in term/late preterm neonates with hypoxic respiratory
failure: estimating the financial impact of earlier use.
AB - OBJECTIVE: We reported recently that early use of inhaled nitric oxide therapy
(iNO) for term and late preterm infants with hypoxic respiratory failure (HRF) at
an oxygenation index (OI) of >=15 and <20 is associated with earlier discharge
from the hospital, relative to babies treated at OI >=25. The objective of the
present analysis is to determine whether earlier use of iNO in this cohort leads
to lower cost of medical care. METHODS: We used a decision-analytic model, which
was developed to compare hospital resource use and costs associated with early
versus standard use of iNO in HRF. The model population included infants with
moderate HRF caused by primary pulmonary hypertension with an OI >=15 and <20. A
hypothetical case population of 1000 patients was assumed and probabilistic
sensitivity analyses were completed where all the clinical inputs into the model
were varied. Two deterministic sensitivity analyses were also completed, one
surrounding the hospital cost inputs and another surrounding the cost of iNO.
RESULTS: Early iNO was associated with fewer hospital days, fewer days of
ventilation and fewer hours on extracorporeal membrane oxygenation (ECMO). In
probabilistic sensitivity analyses, total costs per patient were $88,518 +/-
$7574 and $92,581 +/- $9664 for early iNO and standard iNO, respectively. The
probability of early iNO being cost-effective was approximately 72%, based on a
willingness to pay $100,000 or less to prevent ECMO therapy and/or death. In both
deterministic sensitivity analyses, early iNO was cost-saving. CONCLUSION: Our
analysis shows that early use of iNO at an OI of >=15 and <20 may be associated
with shorter hospitalizations and a decreased cost of care for term/late preterm
infants with HRF associated with pulmonary hypertension. Our results are based on
clinical data from a single trial; future research using data from real-world
practice is warranted.
PMID- 25853868
TI - Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to
bolus insulin both in combination with basal insulin for the treatment of
patients with type 2 diabetes in Norway.
AB - BACKGROUND: Lixisenatide is a potent, selective and short-acting once daily
prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin
and body weight by clinically significant amounts in patients with type 2
diabetes treated with basal insulin, with limited risk of hypoglycemia.
OBJECTIVE: To assess the cost-effectiveness of lixisenatide versus bolus insulin,
both in combination with basal insulin, in patients with type 2 diabetes in
Norway. METHODS: The IMS CORE Diabetes Model, a non-product-specific and
validated simulation model, was used to make clinical and cost projections.
Transition probabilities, risk adjustments and the progression of complication
risk factors were derived from the UK Prospective Diabetes Study, supplemented
with Norwegian data. Patients were assumed to receive combination treatment with
basal insulin, lixisenatide or bolus insulin therapy for 3 years, followed by
intensification of a basal-bolus insulin regimen for their remaining lifetime.
Simulated healthcare costs, taken from the public payer perspective, were derived
from microcosting and diagnosis related groups, discounted at 4% per annum and
reported in Norwegian krone (NOK). Productivity costs were also captured based on
extractions from the Norwegian Labor and Welfare Administration. Health state
utilities were derived from a systematic literature review. Sensitivity and
scenario analyses were performed. RESULTS: Lixisenatide in combination with basal
insulin was associated with increased quality-adjusted life years (QALYs) and
reduced lifetime healthcare costs compared to bolus insulin in combination with
basal insulin in patients with Type 2 diabetes, and can be considered dominant.
The net monetary benefit of lixisenatide versus bolus insulin was NOK 39,369 per
patient. Results were sensitive to discounting, the application of excess body
weight associated disutility and uncertainty surrounding the changes in HbA1c.
CONCLUSIONS: Lixisenatide may be considered an economically efficient therapy in
combination with basal insulin in the Norwegian setting, due to cost savings,
weight loss and associated gains in health-related quality of life.
PMID- 25853869
TI - Finger muscle attachments for an OpenSim upper-extremity model.
AB - We determined muscle attachment points for the index, middle, ring and little
fingers in an OpenSim upper-extremity model. Attachment points were selected to
match both experimentally measured locations and mechanical function (moment
arms). Although experimental measurements of finger muscle attachments have been
made, models differ from specimens in many respects such as bone segment ratio,
joint kinematics and coordinate system. Likewise, moment arms are not available
for all intrinsic finger muscles. Therefore, it was necessary to scale and
translate muscle attachments from one experimental or model environment to
another while preserving mechanical function. We used a two-step process. First,
we estimated muscle function by calculating moment arms for all intrinsic and
extrinsic muscles using the partial velocity method. Second, optimization using
Simulated Annealing and Hooke-Jeeves algorithms found muscle-tendon paths that
minimized root mean square (RMS) differences between experimental and modeled
moment arms. The partial velocity method resulted in variance accounted for (VAF)
between measured and calculated moment arms of 75.5% on average (range from 48.5%
to 99.5%) for intrinsic and extrinsic index finger muscles where measured data
were available. RMS error between experimental and optimized values was within
one standard deviation (S.D) of measured moment arm (mean RMS error = 1.5 mm <
measured S.D = 2.5 mm). Validation of both steps of the technique allowed for
estimation of muscle attachment points for muscles whose moment arms have not
been measured. Differences between modeled and experimentally measured muscle
attachments, averaged over all finger joints, were less than 4.9 mm (within 7.1%
of the average length of the muscle-tendon paths). The resulting non-proprietary
musculoskeletal model of the human fingers could be useful for many applications,
including better understanding of complex multi-touch and gestural movements.
PMID- 25853870
TI - The impact of gender norms on condom use among HIV-positive adults in KwaZulu
Natal, South Africa.
AB - Critical to preventing the spread of HIV is promoting condom use among HIV
positive individuals. Previous studies suggest that gender norms (social and
cultural constructions of the ways that women and men are expected to behave) may
be an important determinant of condom use. However, the relationship has not been
evaluated among HIV-positive women and men in South Africa. We examined gender
norms and condom use at last sex among 550 partnerships reported by 530 sexually
active HIV-positive women (372) and men (158) who had sought care, but not yet
initiated antiretroviral therapy in a high HIV-prevalence rural setting in
KwaZulu-Natal, South Africa between January 2009 and March 2011. Participants
enrolled in the cohort study completed a baseline questionnaire that detailed
their socio-demographic characteristics, socio-economic circumstances, religion,
HIV testing history and disclosure of HIV status, stigma, social capital, gender
norms and self-efficacy. Gender norms did not statistically differ between women
and men (p = 0.18). Overall, condoms were used at last sex in 58% of
partnerships. Although participants disclosed their HIV status in 66% of the
partnerships, 60% did not have knowledge of their partner's HIV status. In
multivariable logistic regression, run separately for each sex, women younger
than 26 years with more equitable gender norms were significantly more likely to
have used a condom at last sex than those of the same age group with inequitable
gender norms (OR = 8.88, 95% CI 2.95-26.75); the association between condom use
and gender norms among women aged 26+ years and men of all ages was not
statistically significant. Strategies to address gender inequity should be
integrated into positive prevention interventions, particularly for younger
women, and supported by efforts at a societal level to decrease gender
inequality.
PMID- 25853871
TI - Assay reproducibility in clinical studies of plasma miRNA.
AB - There are increasing reports of plasma miRNAs as biomarkers of human disease but
few standards in methodologic reporting, leading to inconsistent data. We
systematically reviewed plasma miRNA studies published between July 2013-June
2014 to assess methodology. Six parameters were investigated: time to plasma
extraction, methods of RNA extraction, type of miRNA, quantification, cycle
threshold (Ct) setting, and methods of statistical analysis. We compared these
data with a proposed standard methodologic technique. Beginning with initial
screening for 380 miRNAs using microfluidic array technology and validation in an
additional cohort of patients, we compared 11 miRNAs that exhibited differential
expression between 16 patients with benign colorectal neoplasms (advanced
adenomas) and 16 patients without any neoplasm (controls). Plasma was isolated
immediately, 12, 24, 48, or 72 h following phlebotomy. miRNA was extracted using
two different techniques (Trizol LS with pre-amplification or modified miRNeasy).
We performed Taqman-based RT-PCR assays for the 11 miRNAs with subsequent
analyses using a variable Ct setting or a fixed Ct set at 0.01, 0.03, 0.05, or
0.5. Assays were performed in duplicate by two different operators. RNU6 was the
internal reference. Systematic review yielded 74 manuscripts meeting inclusion
criteria. One manuscript (1.4%) documented all 6 methodological parameters, while
< 5% of studies listed Ct setting. In our proposed standard technique, plasma
extraction <=12 h provided consistent DeltaCt. miRNeasy extraction yielded higher
miRNA concentrations and fewer non-expressed miRNAs compared to Trizol LS (1/704
miRNAs [0.14%] vs 109/704 miRNAs [15%], not expressed, respectively). A fixed Ct
bar setting of 0.03 yielded the most reproducible data, provided that <10% miRNA
were non-expressed. There was no significant intra-operator variability. There
was significant inter-operator variation using Trizol LS extraction, while this
was negligible using modified miRNeasy. For standardized reporting, we recommend
plasma extraction <= 12 h, using modified miRNeasy extraction and utilizing a
0.03 Ct.
PMID- 25853874
TI - World gastroenterology organisation global guidelines: dysphagia--global
guidelines and cascades update September 2014.
PMID- 25853872
TI - Magnetization transfer imaging of suicidal patients with major depressive
disorder.
AB - Magnetization transfer imaging (MTI) provides a quantitative measure of the
macromolecular structural integrity of brain tissue, as represented by
magnetization transfer ratio (MTR). In this study, we utilized MTI to identify
biophysical alterations in MDD patients with a history of suicide attempts
relative to MDD patients without such history. The participants were 36
medication-free MDD patients, with (N = 17) and without (N = 19) a history of a
suicide attempt, and 28 healthy controls matched for age and gender. Whole brain
voxel-based analysis was used to compare MTR across three groups and to analyze
correlations with symptom severity and illness duration. We identified decreased
MTR in left inferior parietal lobule and right superior parietal lobule in
suicide attempters relative to both non-attempters and controls. Non-attempters
also showed significantly reduced MTR in left inferior parietal lobule relative
to controls, as well as an MTR reduction in left cerebellum. These abnormalities
were not correlated with symptom severity or illness duration. Depressed patients
with a history of suicide attempt showed bilateral abnormalities in parietal
cortex compared to nonsuicidal depressed patients and healthy controls. Parietal
lobe abnormalities might cause attentional dysfunction and impaired decision
making to increase risk for suicidal behavior in MDD.
PMID- 25853875
TI - World digestive health day, heartburn: a Global Perspective and Gastro 2015!
PMID- 25853876
TI - Short-term effect of crunch exercise frequency on abdominal muscle endurance.
AB - Despite core exercise programs are broadly used to increase muscle function and
to promote low back health, there is a lack of scientific evidence on some of the
most important characteristics of trunk exercise programs, as for example
training frequency. This study aimed to compare the short-term effect of training
frequencies of 1, 2 and 3 days per week (d/wk) on abdominal muscle endurance in
untrained adolescents. One hundred and eighteen high-school students (59 men and
59 women) with no previous experience in structured abdominal exercise programs
were assigned randomly to groups that trained 1 d/wk (G1; N.=21), 2 d/wk (G2;
N.=27), 3 d/wk (G3; N.=23), or to a control group (CG; N.=47) that did not train.
The training groups performed crunch and cross-crunch exercises 1, 2 or 3 d/wk
during six weeks. Before and after the training period, the bench trunk-curl test
(BTC test) was carried out to assess abdominal muscle endurance. Men obtained
higher BTC test scores than women before and after training. Training frequencies
of 1, 2 and 3 d/wk provided a significant increase in BTC test scores; however,
no significant differences between the three groups' scores were found after
training. Therefore, a small dose of crunch exercise training (1 d/wk) may be
sufficient stimulus to increase abdominal endurance in untrained male and female
adolescents, at least during the first weeks of an abdominal exercise program,
which seems a very relevant finding in terms of time-cost efficiency.
PMID- 25853877
TI - Creatine supplementation alters homocysteine level in resistance trained men.
AB - AIM: This study was conducted to investigate the effects of creatine loading and
resistance training on the homocysteine and lipid profiles of young males.
METHOD: Sixty male University students (22.34 +/- 2.19 years, 1.79 +/- 0.08 m,
77.18 +/- 12.57 kg, 15.48 +/- 4.57% body fat) were randomly divided in to three
groups; control (CG=20), creatine supplement (CEG=20) and placebo (PEG=20). Both
CEG and PEG participated in a same resistance-training regimen and either taking
a creatine supplement (25 g/d for the first 5 days followed 5 g/d thereafter) or
the same amount of placebo for 8 weeks. Participants in CG did not take any
creatine supplementation and not engage any exercise program. After the body
composition were assessed, the homocysteine (Hcy) concentrations, blood lipids,
folic acid and vitamin B12 levels of all the participants were measured at the
beginning and end of the eight weeks of resistance training. RESULTS: The
analysis of the data indicated that the Hcy levels of the CEG after resistance
training and receiving the creatine supplement (9.33 +/- 4.60) was significantly
lower than that of baseline (12.66 +/- 5.89) measurements, F(1,18)=12.28, P=0.00.
No significant differences were seen in the Hcy levels of the PEG (15.01 +/-
10.87) after 8 weeks of training and receiving a placebo (12.46 +/- 12.50),
F(1,16)=4.65, P=0.05. Furthermore, there were no significant differences among
groups in terms of Hcy levels, F(2,52)=1.72, P=0.19. CONCLUSION: The present
study suggests that as well as strength gain; creatine supplementation with
resistance training may afford some protection against emerging cardiovascular
risk factors.
PMID- 25853878
TI - Effects of acute total body resistance exercise on hormonal and cytokines changes
in men and women.
AB - AIM: Sex differences in exercise responses have implications for understanding
sex-specific adaptations to exercise for performance and health. The purpose of
this study was to verify the acute effects of a full body resistance exercise
protocol on growth hormone (GH), testosterone (TT), cortisol, interleukin (IL)-6
and IL-10 in men and women. METHODS: Fourteen healthy volunteers (7 men and 7
women taking oral contraceptives) active and recreationally trained in resistance
exercise were subjected to a resistance exercise session (3x8-10 RM) composed of
10 exercises with rests periods of 90-120 seconds between sets. GH, TT, cortisol,
IL-6 and IL-10 were assessed at pre-, immediate post- (IP) and 30 min
postprotocol. RESULTS: Both men and women had a similar increase in GH (P<0.05)
at IP in response to exercise. Significant effects of interaction between sex and
time were observed for TT, cortisol and IL-6. In the men, an increase from pre
was noted at IP and 30 min for TT, cortisol and IL-6. In the women there was no
change in TT, cortisol and IL-6 concentration. There was no change in IL-10.
CONCLUSION: Our findings indicate a difference between men and women taking oral
contraceptives in TT, cortisol and IL-6 responsiveness to the same full body
resistance exercise protocol.
PMID- 25853879
TI - Acute exercise increases hippocampal TNF-alpha, Caspase-3 and Caspase-7
expression in healthy young and older mice.
AB - AIM: Regular exercise may protect against cognitive decline by preventing central
inflammation. The effect of an acute exercise bout on central cytokine and
apoptotic protein expression is not known. The brain may be protected from
transient oxidative stress such as that induced by acute-exercise. The purpose of
this exploratory study was to determine the effect of a single bout of intense
exercise on hippocampal expression of inflammatory mediators (TNF-alpha) and
apoptotic proteins (caspase-3, caspase-7), and to evaluate any potential age
related differences. METHODS: Using a C57BL/6 mouse model (N.=98), we evaluated
the effect of an acute exercise bout (90 minutes of treadmill running: 10 min
warm-up, 30 min at 22 m.min-1, 30 min at 25 m.min-1, and 30 min at 28 m.min-1, 2
degrees slope) on hippocampal inflammation in young (3-4 months), middle-aged
(13-14 months) and older (16-17 months) C57BL/6 mice. RESULTS: Our results show
post-exercise increases in hippocampal TNF-alpha and caspase-3/7 in each age
group (main effect of acute exercise, P<0.05). Older mice displayed higher TNF
alpha (main effect of age, P<0.05) expression compared with younger animals at
baseline. Young mice demonstrated greater increases in caspase-7 following acute
exercise, compared to older mice (interaction effect for caspase-7, P<0.05).
CONCLUSION: Given the relationship between aging, inflammation and
neurodegenerative disease, and the protective effects of exercise, we cautiously
propose that acute-exercise induced inflammation may be a normal physiologic
response that elicits a favorable (anti-inflammatory) hippocampal environment.
PMID- 25853880
TI - Solomon Islands largest hawksbill turtle rookery shows signs of recovery after
150 years of excessive exploitation.
AB - The largest rookery for hawksbill turtles in the oceanic South Pacific is the
Arnavon Islands, which are located in the Manning Strait between Isabel and
Choiseul Province, Solomon Islands. The history of this rookery is one of
overexploitation, conflict and violence. Throughout the 1800s Roviana headhunters
from New Georgia repeatedly raided the Manning Strait to collect hawksbill shell
which they traded with European whalers. By the 1970s the Arnavons hawksbill
population was in severe decline and the national government intervened,
declaring the Arnavons a sanctuary in 1976. But this government led initiative
was short lived, with traditional owners burning down the government
infrastructure and resuming intensive harvesting in 1982. In 1991 routine beach
monitoring and turtle tagging commenced at the Arnavons along with extensive
community consultations regarding the islands' future, and in 1995 the Arnavon
Community Marine Conservation Area (ACMCA) was established. Around the same time
national legislation banning the sale of all turtle products was passed. This
paper represents the first analysis of data from 4536 beach surveys and 845
individual turtle tagging histories obtained from the Arnavons between 1991-2012.
Our results and the results of others, reveal that many of the hawksbill turtles
that nest at the ACMCA forage in distant Australian waters, and that nesting on
the Arnavons occurs throughout the year with peak nesting activity coinciding
with the austral winter. Our results also provide the first known evidence of
recovery for a western pacific hawksbill rookery, with the number of nests laid
at the ACMCA and the remigration rates of turtles doubling since the
establishment of the ACMCA in 1995. The Arnavons case study provides an example
of how changes in policy, inclusive community-based management and long term
commitment can turn the tide for one of the most charismatic and endangered
species on our planet.
PMID- 25853881
TI - Relaxation effect of abacavir on rat basilar arteries.
AB - BACKGROUND: The use of abacavir has been linked with increased cardiovascular
risk in patients with human immunodeficiency virus infection; however, the
mechanism involved remains unclear. We hypothesize that abacavir may impair
endothelial function. In addition, based on the structural similarity between
abacavir and adenosine, we propose that abacavir may affect vascular
contractility through endogenous adenosine release or adenosine receptors in
blood vessels. METHODS: The relaxation effect of abacavir on rat basilar arteries
was studied using the myograph technique. Cyclic GMP and AMP levels were measured
by immunoassay. The effects of abacavir on nucleoside transporters were studied
using radiolabeled nucleoside uptake experiments. Ecto-5' nucleotidase activity
was determined by measuring the generation of inorganic phosphate using adenosine
monophosphate as the substrate. RESULTS: Abacavir induced the relaxation of rat
basilar arteries in a concentration-dependent manner. This relaxation was
abolished when endothelium was removed. In addition, the relaxation was
diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase
inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also
increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was
also abolished by adenosine A2 receptor blockers. However, abacavir had no effect
on ecto-5' nucleotidase and nucleoside transporters. Short-term and long-term
treatment of abacavir did not affect acetylcholine-induced relaxation in rat
basilar arteries. CONCLUSION: Abacavir induces acute endothelium-dependent
relaxation of rat basilar arteries, probably through the activation of adenosine
A2 receptors in endothelial cells, which subsequently leads to the release of
nitric oxide, resulting in activation of the cyclic guanosine
monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells.
It is speculated that abacavir-induced cardiovascular risk may not be related to
endothelial dysfunction as abacavir does not impair relaxation of blood vessels.
The most likely explanation of increased cardiovascular risk may be increased
platelet aggregation as suggested by other studies.
PMID- 25853882
TI - White matter integrity supports BOLD signal variability and cognitive performance
in the aging human brain.
AB - Decline in cognitive performance in old age is linked to both suboptimal neural
processing in grey matter (GM) and reduced integrity of white matter (WM), but
the whole-brain structure-function-cognition associations remain poorly
understood. Here we apply a novel measure of GM processing-moment-to-moment
variability in the blood oxygenation level-dependent signal (SDBOLD)-to study the
associations between GM function during resting state, performance on four main
cognitive domains (i.e., fluid intelligence, perceptual speed, episodic memory,
vocabulary), and WM microstructural integrity in 91 healthy older adults (aged 60
80 years). We modeled the relations between whole-GM SDBOLD with cognitive
performance using multivariate partial least squares analysis. We found that
greater SDBOLD was associated with better fluid abilities and memory. Most of
regions showing behaviorally relevant SDBOLD (e.g., precuneus and insula) were
localized to inter- or intra-network "hubs" that connect and integrate segregated
functional domains in the brain. Our results suggest that optimal dynamic range
of neural processing in hub regions may support cognitive operations that
specifically rely on the most flexible neural processing and complex cross-talk
between different brain networks. Finally, we demonstrated that older adults with
greater WM integrity in all major WM tracts had also greater SDBOLD and better
performance on tests of memory and fluid abilities. We conclude that SDBOLD is a
promising functional neural correlate of individual differences in cognition in
healthy older adults and is supported by overall WM integrity.
PMID- 25853884
TI - Visible-light-promoted remote C(sp(3))-H amidation and chlorination.
AB - A visible-light-promoted C(sp(3))-H amidation and chlorination of N
chlorosulfonamides (NCSs) is reported. This remote C(sp(3))-H functionalization
can be achieved in weak basic solution at room temperature with as little as 0.1
mol % of a photocatalyst. A variety of nitrogen-containing heterocycles (up to
94% yield) and chlorides (up to 93% yield) are prepared from NCSs. Late-stage
C(sp(3))-H functionalization of complex and biologically important (-)-cis
myrtanylamine and (+)-dehydroabietylamine derivatives can also be achieved with
excellent yields and regioselectivity.
PMID- 25853883
TI - Transcript and protein expression decoupling reveals RNA binding proteins and
miRNAs as potential modulators of human aging.
AB - BACKGROUND: In studies of development and aging, the expression of many genes has
been shown to undergo drastic changes at mRNA and protein levels. The connection
between mRNA and protein expression level changes, as well as the role of
posttranscriptional regulation in controlling expression level changes in
postnatal development and aging, remains largely unexplored. RESULTS: Here, we
survey mRNA and protein expression changes in the prefrontal cortex of humans and
rhesus macaques over developmental and aging intervals of both species'
lifespans. We find substantial decoupling of mRNA and protein expression levels
in aging, but not in development. Genes showing increased mRNA/protein disparity
in primate brain aging form expression patterns conserved between humans and
macaques and are enriched in specific functions involving mammalian target of
rapamycin (mTOR) signaling, mitochondrial function and neurodegeneration.
Mechanistically, aging-dependent mRNA/protein expression decoupling could be
linked to a specific set of RNA binding proteins and, to a lesser extent, to
specific microRNAs. CONCLUSIONS: Increased decoupling of mRNA and protein
expression profiles observed in human and macaque brain aging results in specific
co-expression profiles composed of genes with shared functions and shared
regulatory signals linked to specific posttranscriptional regulators. Genes
targeted and predicted to be targeted by the aging-dependent posttranscriptional
regulation are associated with biological processes known to play important roles
in aging and lifespan extension. These results indicate the potential importance
of posttranscriptional regulation in modulating aging-dependent changes in humans
and other species.
PMID- 25853885
TI - Effect of genome and environment on metabolic and inflammatory profiles.
AB - Twin and family studies have established the contribution of genetic factors to
variation in metabolic, hematologic and immunological parameters. The majority of
these studies analyzed single or combined traits into pre-defined syndromes. In
the present study, we explore an alternative multivariate approach in which a
broad range of metabolic, hematologic, and immunological traits are analyzed
simultaneously to determine the resemblance of monozygotic (MZ) twin pairs, twin
spouse pairs and unrelated, non-cohabiting individuals. A total of 517
participants from the Netherlands Twin Register, including 210 MZ twin pairs and
64 twin-spouse pairs, took part in the study. Data were collected on body
composition, blood pressure, heart rate, and multiple biomarkers assessed in
fasting blood samples, including lipid levels, glucose, insulin, liver enzymes,
hematological measurements and cytokine levels. For all 51 measured traits, pair
wise Pearson correlations, correcting for family relatedness, were calculated
across all the individuals in the cohort. Hierarchical clustering techniques were
applied to group the measured traits into sub-clusters based on similarity. Sub
clusters were observed among metabolic traits and among inflammatory markers. We
defined a phenotypic profile as the collection of all the traits measured for a
given individual. Average within-pair similarity of phenotypic profiles was
determined for the groups of MZ twin pairs, spouse pairs and pairs of unrelated
individuals. The average similarity across the full phenotypic profile was higher
for MZ twin pairs than for spouse pairs, and lowest for pairs of unrelated
individuals. Cohabiting MZ twins were more similar in their phenotypic profile
compared to MZ twins who no longer lived together. The correspondence in the
phenotypic profile is therefore determined to a large degree by familial, mostly
genetic, factors, while household factors contribute to a lesser degree to
profile similarity.
PMID- 25853886
TI - ALDB: a domestic-animal long noncoding RNA database.
AB - BACKGROUND: Long noncoding RNAs (lncRNAs) have attracted significant attention in
recent years due to their important roles in many biological processes. Domestic
animals constitute a unique resource for understanding the genetic basis of
phenotypic variation and are ideal models relevant to diverse areas of biomedical
research. With improving sequencing technologies, numerous domestic-animal
lncRNAs are now available. Thus, there is an immediate need for a database
resource that can assist researchers to store, organize, analyze and visualize
domestic-animal lncRNAs. RESULTS: The domestic-animal lncRNA database, named
ALDB, is the first comprehensive database with a focus on the domestic-animal
lncRNAs. It currently archives 12,103 pig intergenic lncRNAs (lincRNAs), 8,923
chicken lincRNAs and 8,250 cow lincRNAs. In addition to the annotations of
lincRNAs, it offers related data that is not available yet in existing lncRNA
databases (lncRNAdb and NONCODE), such as genome-wide expression profiles and
animal quantitative trait loci (QTLs) of domestic animals. Moreover, a collection
of interfaces and applications, such as the Basic Local Alignment Search Tool
(BLAST), the Generic Genome Browser (GBrowse) and flexible search
functionalities, are available to help users effectively explore, analyze and
download data related to domestic-animal lncRNAs. CONCLUSIONS: ALDB enables the
exploration and comparative analysis of lncRNAs in domestic animals. A user
friendly web interface, integrated information and tools make it valuable to
researchers in their studies. ALDB is freely available from
http://res.xaut.edu.cn/aldb/index.jsp.
PMID- 25853888
TI - Ornaments reveal resistance of North European cultures to the spread of farming.
AB - The transition to farming is the process by which human groups switched from
hunting and gathering wild resources to food production. Understanding how and to
what extent the spreading of farming communities from the Near East had an impact
on indigenous foraging populations in Europe has been the subject of lively
debates for decades. Ethnographic and archaeological studies have shown that
population replacement and admixture, trade, and long distance diffusion of
cultural traits lead to detectable changes in symbolic codes expressed by
associations of ornaments on the human body. Here we use personal ornaments to
document changes in cultural geography during the Mesolithic-Neolithic
transition. We submitted a binary matrix of 224 bead-types found at 212 European
Mesolithic and 222 Early Neolithic stratigraphic units to a series of spatial and
multivariate analyses. Our results reveal consistent diachronic and geographical
trends in the use of personal ornaments during the Neolithisation. Adoption of
novel bead-types combined with selective appropriation of old attires by incoming
farmers is identified in Southern and Central Europe while cultural resistance
leading to the nearly exclusive persistence of indigenous personal ornaments
characterizes Northern Europe. We argue that this pattern reflects two distinct
cultural trajectories with different potential for gene flow.
PMID- 25853887
TI - Hunting for the LCT-13910*T allele between the Middle Neolithic and the Middle
Ages suggests its absence in dairying LBK people entering the Kuyavia region in
the 8th millennium BP.
AB - Populations from two medieval sites in Central Poland, Stary Brzesc Kujawski-4
(SBK-4) and Gruczno, represented high level of lactase persistence (LP) as
followed by the LCT-13910*T allele's presence (0.86 and 0.82, respectively). It
was twice as high as in contemporaneous Cedynia (0.4) and Srodka (0.43), both
located outside the region, higher than in modern inhabitants of Poland (0.51)
and almost as high as in modern Swedish population (0.9). In an attempt to
explain the observed differences its frequency changes in time were followed
between the Middle Neolithic and the Late Middle Ages in successive dairying
populations on a relatively small area (radius ~60km) containing the two sites.
The introduction of the T allele to Kuyavia 7.4 Ka BP by dairying LBK people is
not likely, as suggested by the obtained data. It has not been found in any of
Neolithic samples dated between 6.3 and 4.5 Ka BP. The identified frequency
profile indicates that both the introduction and the beginning of selection could
have taken place approx. 4 millennia after first LBK people arrived in the
region, shifting the value of LP frequency from 0 to more than 0.8 during less
than 130 generations. We hypothesize that the selection process of the T allele
was rather rapid, starting just after its introduction into already milking
populations and operated via high rates of fertility and mortality on children
after weaning through life-threatening conditions, favoring lactose-tolerant
individuals. Facing the lack of the T allele in people living on two great
European Neolithization routes, the Danubian and Mediterranean ones, and based on
its high frequency in northern Iberia, its presence in Scandinavia and estimated
occurrence in Central Poland, we propose an alternative Northern Route of its
spreading as very likely. None of the successfully identified nuclear alleles
turned out to be deltaF508 CFTR.
PMID- 25853889
TI - MYB elongation is regulated by the nucleic acid binding of NFkappaB p50 to the
intronic stem-loop region.
AB - MYB transcriptional elongation is regulated by an attenuator sequence within
intron 1 that has been proposed to encode a RNA stem loop (SLR) followed by a
polyU tract. We report that NFkappaBp50 can bind the SLR polyU RNA and promote
MYB transcriptional elongation together with NFkappaBp65. We identified a
conserved lysine-rich motif within the Rel homology domain (RHD) of NFkappaBp50,
mutation of which abrogated the interaction of NFkappaBp50 with the SLR polyU and
impaired NFkappaBp50 mediated MYB elongation. We observed that the TAR RNA
binding region of Tat is homologous to the NFkappaBp50 RHD lysine-rich motif, a
finding consistent with HIV Tat acting as an effector of MYB transcriptional
elongation in an SLR dependent manner. Furthermore, we identify the DNA binding
activity of NFkappaBp50 as a key component required for the SLR polyU mediated
regulation of MYB. Collectively these results suggest that the MYB SLR polyU
provides a platform for proteins to regulate MYB and reveals novel nucleic acid
binding properties of NFkappaBp50 required for MYB regulation.
PMID- 25853890
TI - A systematic review of factors influencing student ratings in undergraduate
medical education course evaluations.
AB - BACKGROUND: Student ratings are a popular source of course evaluations in
undergraduate medical education. Data on the reliability and validity of such
ratings have mostly been derived from studies unrelated to medical education.
Since medical education differs considerably from other higher education
settings, an analysis of factors influencing overall student ratings with a
specific focus on medical education was needed. METHODS: For the purpose of this
systematic review, online databases (PubMed, PsycInfo and Web of Science) were
searched up to August 1st, 2013. Original research articles on the use of student
ratings in course evaluations in undergraduate medical education were eligible
for inclusion. Included studies considered the format of evaluation tools and
assessed the association of independent and dependent (i.e., overall course
ratings) variables. Inclusion and exclusion criteria were checked by two
independent reviewers, and results were synthesised in a narrative review.
RESULTS: Twenty-five studies met the inclusion criteria. Qualitative research (2
studies) indicated that overall course ratings are mainly influenced by student
satisfaction with teaching and exam difficulty rather than objective determinants
of high quality teaching. Quantitative research (23 studies) yielded various
influencing factors related to four categories: student characteristics, exposure
to teaching, satisfaction with examinations and the evaluation process itself.
Female gender, greater initial interest in course content, higher exam scores and
higher satisfaction with exams were associated with more positive overall course
ratings. CONCLUSIONS: Due to the heterogeneity and methodological limitations of
included studies, results must be interpreted with caution. Medical educators
need to be aware of various influences on student ratings when developing data
collection instruments and interpreting evaluation results. More research into
the reliability and validity of overall course ratings as typically used in the
evaluation of undergraduate medical education is warranted.
PMID- 25853891
TI - Expanding the species and chemical diversity of Penicillium section
Cinnamopurpurea.
AB - A set of isolates very similar to or potentially conspecific with an unidentified
Penicillium isolate NRRL 735, was assembled using a BLAST search of ITS
similarity among described (GenBank) and undescribed Penicillium isolates in our
laboratories. DNA was amplified from six loci of the assembled isolates and
sequenced. Two species in section Cinnamopurpurea are self-compatible sexual
species, but the asexual species had polymorphic loci suggestive of sexual
reproduction and variation in conidium size suggestive of ploidy level
differences typical of heterothallism. Accordingly we use genealogical
concordance analysis, a technique valid only in heterothallic organisms, for
putatively asexual species. Seven new species were revealed in the analysis and
are described here. Extrolite analysis showed that two of the new species, P.
colei and P. monsserratidens produce the mycotoxin citreoviridin that has
demonstrated pharmacological activity against human lung tumors. These isolates
could provide leads in pharmaceutical research.
PMID- 25853893
TI - Repeated sprint performance and metabolic recovery curves: effects of aerobic and
anaerobic characteristics.
AB - To examine the influence of aerobic and anaerobic indices on repeated sprint (RS)
performance and ability (RSA), 8 sprinters (SPR), 8 endurance runners (END), and
8 active participants (ACT) performed the following tests: (i) incremental test;
(ii) 1-min test to determine first decay time constant of pulmonary oxygen uptake
off-kinetics and parameters related to anaerobic energy supply, lactate exchange,
and removal abilities from blood lactate kinetics; and (iii) RS test (ten 35-m
sprints, departing every 20 s) to determine best (RSbest) and mean (RSmean)
sprint times and percentage of sprint decrement (%Dec). While SPR had a 98%-100%
likelihood of having the fastest RSbest (Cohen's d of 1.8 and 1.4 for ACT and
END, respectively) and RSmean (2.1 and 0.9 for ACT and END, respectively), END
presented a 97%-100% likelihood of having the lowest %Dec (0.9 and 2.2 for ACT
and SPR, respectively). RSmean was very largely correlated with RSbest (r=0.85)
and moderately correlated with estimates of anaerobic energy supply (r=-0.40 to
0.49). RSmean adjusted for RSbest (which indirectly reflects RSA) was largely
correlated with lactate exchange ability (r=0.55). Our results confirm the
importance of locomotor- and anaerobic-related variables to RS performance, and
highlight the importance of disposal of selected metabolic by-products to RSA.
PMID- 25853892
TI - Apparent time interval of visual stimuli is compressed during fast hand movement.
AB - The influence of body movements on visual time perception is receiving increased
attention. Past studies showed apparent expansion of visual time before and after
the execution of hand movements and apparent compression of visual time during
the execution of eye movements. Here we examined whether the estimation of sub
second time intervals between visual events is expanded, compressed, or
unaffected during the execution of hand movements. The results show that hand
movements, at least the fast ones, reduced the apparent time interval between
visual events. A control experiment indicated that the apparent time compression
was not produced by the participants' involuntary eye movements during the hand
movements. These results, together with earlier findings, suggest hand movement
can change apparent visual time either in a compressive way or in an expansive
way, depending on the relative timing between the hand movement and visual
stimulus.
PMID- 25853894
TI - A Nonclassical Monocyte Phenotype in Peripheral Blood is Associated with
Nonalcoholic Fatty Liver Disease: A Report from an EMIL Subcohort.
AB - Nonalcoholic fatty liver disease (NAFLD) as the prototypic hepatic manifestation
of metabolic syndrome is an independent risk factor for cardiovascular disease.
Our study was designed to investigate the association between NAFLD and
alteration in monocyte subsets as hallmark of cardiovascular disease. Seventy
three "Echinococcus Multilocularis and other medical diseases in Leutkirch"
(EMIL) population-based cohort participants (mean observation period 11 years)
were selected to study their monocyte phenotype by multiparameter flow cytometry.
NAFLD was diagnosed using standard ultrasound based criteria excluding other
causes of fatty liver disease. Three monocyte subsets ("classical" CD14++ CD16-,
"intermediate" CD14++ CD16+, "nonclassical" CD14+CD16++ monocytes), and surface
markers (CD36 and CD9) were determined. Classical risk markers covering
inflammatory and dysmetabolic characters were also determined. Forty-three out of
73 subjects revealed a stable clinical phenotype, namely 17 subjects revealed
NAFLD, whereas 26 subjects showed no fatty liver disease. Compared to the
nonfatty liver group, the nonclassical monocyte fraction (p=0.049), total
monocyte fraction and count were increased in NAFLD probands (p=0.028, and 0.035,
respectively), while classical monocyte fraction (p=0.034) was decreased. Total
monocyte fraction, nonclassical monocyte fraction, and waist circumstance were
independent risk factors for NAFLD. The nonclassical monocyte fraction and
classical monocyte fraction were significantly correlated with waist-to-hip
ratio. This pilot long-term follow-up study suggests that nonclassical monocyte
fraction and total monocyte fraction might have potential as a prognostic and
modifiable biomarker in NFALD patients. This novel marker set might therefore be
of interest to monitor druggable inflammatory pathways in individuals with
hepatic manifestation of the metabolic syndrome.
PMID- 25853895
TI - Gender development and sexuality in disorders of sex development.
AB - Understanding psychological development in individuals with disorders of sex
development (DSD) is important for optimizing their clinical care and for
identifying paths to competence and health in all individuals. In this paper, we
focus on psychological outcomes likely to be influenced by processes of physical
sexual differentiation that may be atypical in DSD, particularly characteristics
related to being male or female (those that show sex differences in the general
population, gender identity, and sexuality). We review evidence suggesting that
(a) early androgens facilitate several aspects of male-typed behavior, with large
effects on activity interests, and moderate effects on some social and personal
behaviors (including sexual orientation) and spatial ability; (b) gender
dysphoria and gender change occur more frequently in individuals with DSD than in
the general population, with rates varying in relation to syndrome, initial
gender assignment, and medical treatment; and (c) sexual behavior may be affected
by DSD through several paths related to the condition and treatment, including
reduced fertility, physical problems associated with genital ambiguity, social
stigmatization, and hormonal variations. We also consider limitations to current
work and challenges to studying gender and sexuality in DSD. We conclude with
suggestions for a research agenda and a proposed research framework.
PMID- 25853896
TI - Promoting Shared Decision Making in Disorders of Sex Development (DSD): Decision
Aids and Support Tools.
AB - Specific complaints and grievances from adult patients with disorders of sex
development (DSD), and their advocates center around the lack of information or
misinformation they were given about their condition and feeling stigmatized and
shamed by the secrecy surrounding their condition and its management. Many also
attribute poor sexual function to damaging genital surgery and/or repeated,
insensitive genital examinations. These reports suggest the need to reconsider
the decision-making process for the treatment of children born with DSD. This
paper proposes that shared decision making, an important concept in adult health
care, be operationalized for the major decisions commonly encountered in DSD care
and facilitated through the utilization of decision aids and support tools. This
approach may help patients and their families make informed decisions that are
better aligned with their personal values and goals. It may also lead to greater
confidence in decision making with greater satisfaction and less regret. A brief
review of the past and current approach to DSD decision making is provided, along
with a review of shared decision making and decision aids and support tools. A
case study explores the need and potential utility of this suggested new
approach.
PMID- 25853897
TI - Regioselective Synthesis of Highly Substituted Imidazoles via the Sequential
Reaction of Allenyl Sulfonamides and Amines.
AB - A novel synthesis of imidazoles from electron-withdrawing group-substituted